title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Acute chest pain emergencies - spouses' prehospital experiences. | The call to the Emergency Medical Dispatch Centre is often a person's first contact with the health-care system in cases of acute illness or injury and acute chest pain is a common reason for calling. The aim was to illuminate how spouses to persons with acute chest pain experienced the alarm situation, the emergency call and the prehospital emergency care. Interviews were conducted with nineteen spouses. A phenomenological-hermeneutic approach was used for the analyses. The themes responsibility and uneasiness emerged as well as an overall theme of aloneness. Being a spouse to a person in need of acute medical and nursing assistance was interpreted as "Being responsible and trying to preserve life" and "Being able to manage the uneasiness and having trust in an uncertain situation." When their partners' life was at risk the spouses were in an escalating spiral of worry, uncertainty, stress, fear of loss, feeling of loneliness and desperation. They had to manage emotional distress and felt compelled to act to preserve life, a challenging situation. | 18,929,341 |
An audit of compliance with the sepsis resuscitation care bundle in patients admitted to A&E with severe sepsis or septic shock. | Severe sepsis and septic shock are syndromes resulting in a systemic inflammatory response and the dysfunction of one or more organs following infection. The Surviving Sepsis Campaign is an international effort to reduce mortality in severe sepsis and septic shock by 25% by 2009 using a care bundle approach. It comprises evidenced-based interventions to be carried out within 6h of onset of sepsis. We conducted a prospective observational audit of 32 consecutive adult patients with severe sepsis or septic shock admitted via the A&E of a district general hospital. The compliance rate against each element, and overall compliance to the 6-h bundle were obtained. Patients' ages ranged from 55 to 75 years with 53% being male. Overall compliance was 19%. Arterial lactate was undertaken 100% of the time, and only just over half received an appropriate fluid challenge. Administration of an antibiotic was also very slow. Local recommendations include improvements to the track and trigger scoring system in A&E to improve recognition of sick patients, ensuring the doctor responsible for prescribing the antibiotic will administer it, and increasing awareness of the surviving sepsis campaign via education and training of all A&E staff. Given current evidence greater compliance to the care bundle may well improve patient outcomes for this client group. | 18,929,343 |
Prospective study of intravitreal ranibizumab as a treatment for decreased visual acuity secondary to central retinal vein occlusion. | To evaluate intravitreal injection of ranibizumab as a potential treatment for decreased visual acuity (VA) secondary to central retinal vein occlusion (CRVO). Prospective, interventional case series. Patients with CRVO prospectively recruited from a practice were administered intravitreal ranibizumab 0.5 mg (Lucentis; Genentech Inc, South San Francisco, California, USA) at baseline and monthly for two additional doses. The patients were given additional ranibizumab if they had macular edema as determined by optical coherence tomography or any new intraretinal hemorrhage. Patients were evaluated for number of required injections, side effects, changes in VA, and macular thickness. There were 20 eyes of 20 patients who at baseline had a mean age of 72.1 years, a mean VA of 45.8 Early Treatment of Diabetic Retinopathy letters, and a mean central macular thickness of 574.6 microm. Of the 20 eyes, five previously had received intravitreal triamcinolone and 11 had received intravitreal bevacizumab (Avastin; Genentech Inc). At 12 months of follow-up, the mean VA improved to 64.3 letters and the central macular thickness decreased to 186 microm (both different than baseline values; P < .001) using a mean of 8.5 injections. The change in macular thickness was not correlated with the change in VA. In one patient with a history of transient ischemic attack, an ischemic stroke developed but no sequela resulted. In another patient, vitreomacular traction developed, but the patient had improved acuity as compared with baseline. There were no infections, retinal tears, or detachments. Intravitreal ranibizumab used over a period of one year improved mean VA, with low rates of adverse events, in patients with CRVO. | 18,929,354 |
Wound complications at the groin after peripheral arterial surgery sparing the lymphatic tissue: a double-blind randomized clinical trial. | The groin incision after arterial reconstructive surgery is most likely at risk for infectious or lymphatic wound complications. Theoretically; sparing lymphatic tissue by a lateral approach to the femoral artery should minimize these. The aim of this study was to assess the incidence of wound complications after the lateral versus the direct approach of the common femoral artery. The study population included all patients who underwent an exploration of the common femoral artery between May 2002 and December 2005. After 6 weeks, no statistical differences in the occurrence of wound complications could be shown. A wound infection was present after 6 weeks in 6.1% in the direct group versus 6.0% in the lateral group. Lymphorrhea was persistent in 3.1% in the direct group versus 5.0% in the lateral group. Using a lateral vertical incision for the approach of the common femoral artery did not decrease the incidence of postoperative wound complications. | 18,929,355 |
Does the reuse of PET bottles during solar water disinfection pose a health risk due to the migration of plasticisers and other chemicals into the water? | Solar water disinfection (SODIS) is a simple, effective and inexpensive water treatment procedure suitable for application in developing countries. Microbially contaminated water is filled into transparent polyethylene terephthalate (PET) plastic bottles and exposed to full sunlight for at least 6h. Solar radiation and elevated temperature destroy pathogenic germs efficiently. Recently, concerns have been raised insinuating a health risk by chemicals released from the bottle material polyethylene terephthalate (PET). Whereas the safety of PET for food packaging has been assessed in detail, similar investigations for PET bottles used under conditions of the SODIS treatment were lacking until now. In the present study, the transfer of organic substances from PET to water was investigated under SODIS conditions using used colourless transparent beverage bottles of different origin. The bottles were exposed to sunlight for 17h at a geographical latitude of 47 degrees N. In a general screening of SODIS treated water, only food flavour constituents of previous bottle contents could be identified above a detection limit of 1 microg/L. Quantitative determination of plasticisers di(2-ethylhexyl)adipate (DEHA) and di(2-ethylhexyl)phthalate (DEHP) revealed maximum concentrations of 0.046 and 0.71 microg/L, respectively, being in the same range as levels of these plasticisers reported in studies on commercial bottled water. Generally, only minor differences in plasticiser concentrations could be observed in different experimental setups. The most decisive factor was the country of origin of bottles, while the impact of storage conditions (sunlight exposure and temperature) was less distinct. Toxicological risk assessment of maximum concentrations revealed a minimum safety factor of 8.5 and a negligible carcinogenic risk of 2.8 x 10(-7) for the more critical DEHP. This data demonstrate that the SODIS procedure is safe with respect to human exposure to DEHA and DEHP. | 18,929,387 |
The "Red Lady" ages gracefully: new ultrafiltration AMS determinations from Paviland. | The "Red Lady" partial human skeleton found at Goat's Hole, Paviland, in south Wales by William Buckland in 1823 is one of the iconic relics of the British Paleolithic. Originally thought to be Roman, a Paleolithic age has been suspected from the middle of the 19th century. Several attempts have been made at directly radiocarbon dating the "Red Lady," and here we report new determinations that suggest that it is, by a significant margin, the oldest of a group of 'rich,' Mid-Upper Paleolithic burials. We list similar Gravettian-aged burials from Europe, which have been dated recently for comparison. In this paper, we also reconsider the chronology of human use of the cave, apart from as a burial location. | 18,929,395 |
Haemostatic profile of full-term, healthy, small for gestational age neonates. | Small for Gestational Age (SGA) neonates often appear with haemostatic alterations, principally due to hepatic dysfunction that results from chronic intrauterine hypoxia. Polycythaemia and thrombocytopenia are common findings in this neonatal population. We performed a comparison of coagulation, natural inhibitors and fibrinolysis between SGA and Appropriate for Gestational Age (AGA) infants born full term [gestational age (G.A.) >37 weeks]. Study population consisted of 188 healthy newborns, 90 of whom were SGA (62 females and 28 males), while the rest were the control group (44 females and 54 males). Blood samples were obtained within 30 minutes following birth and before the administration of vitamin K. Investigation included: PT, INR, APTT, fibrinogen, coagulation factors II, V, VII, VIII, IX, X, XI, XII, vWillebrand factor, protein C and free protein S, antithrombin (AT), APCR, tPA and PAI-1. The independent t-test was used to compare the differences between the values of haemostatic parameters. Statistical analysis revealed a significant prolongation in PT, INR, elevated levels of tPA (p<0.015, 0.01 and 0.002 respectively) and a decrease in the values of XII and free protein S (p<0.045 and 0.007 respectively) in SGA full term neonates. The two groups had similar demographic characteristics (except birth weight), without significant differences in the values of other haemostatic parameters. Despite of statistically significant differences in PT, INR, values of tPA, XII and free protein S, levels of haemostatic factors range within laboratory references for healthy full term newborns. These findings were not accompanied with clinical manifestations of altered haemostasis. | 18,929,397 |
Influence of inflammation and aging on macrophage inhibitory cytokine-1 gene expression in rat ventral prostate. | We have previously reported that the macrophage inhibitory cytokine-1 (MIC-1) gene is downregulated in human symptomatic benign prostatic hyperplasia. The aim of this study was to investigate the histologic changes and MIC-1 gene expression in the prostate of young nonbacterial prostatitis model (Y-NBP) and aging rats. A total of 35 Wistar male rats, 13 weeks old, were castrated and subjected to (a) castration alone for 14 days, (b) Y-NBP-14d (0.25 mg/2 mL/kg beta-estradiol injection for 14 days), or (c) Y-NBP-30d (beta-estradiol injection for 30 days). A total of 5 male rats, 10 months old, were also analyzed. We used 21 male rats, 13 weeks old, who had undergone sham surgery as the controls. The ventral lobes of the prostate were histologically examined with Masson's trichrome staining or immunostaining using an anti-macrophage antibody. The MIC-1 mRNA levels were quantitatively assessed using real-time reverse transcriptase-polymerase chain reaction. The MIC-1 gene mRNA levels in the castration alone, Y-NBP-14d, and Y-NBP-30d rat prostates were greater than those in the control rats (P < .005). In contrast, those of the 10-month-old rats were lower than those of the controls (P = .0093). The mean stroma-to-epithelium ratio in the Y-NBP-30d rats, 10-month-old rats, and 13-week-old controls was 1.28, 0.26, and 0.10, respectively (Y-NBP-30d vs 10-month-old rats, P = .0008; 10-month-old vs 13-week-old rats, P = .001). The number of infiltrating macrophages in the Y-NBP-14d, Y-NBP-30d, and 10-month-old rats was greater than that of the 13-week-old controls (P < .001). Castration causes induction of MIC-1 gene expression. Estradiol treatment has little effect on MIC-1 gene expression but causes a significant increase in the stroma-to-epithelium ratio. The aging rat prostate is more similar to human benign prostatic hyperplasia than is the Y-NBP model in light of MIC-1 gene expression and histologic changes. | 18,929,399 |
The development of peptide-based interfacial biomaterials for generating biological functionality on the surface of bioinert materials. | Biomaterials used in implants have traditionally been selected based on their mechanical properties, chemical stability, and biocompatibility. However, the durability and clinical efficacy of implantable biomedical devices remain limited in part due to the absence of appropriate biological interactions at the implant interface and the lack of integration into adjacent tissues. Herein, we describe a robust peptide-based coating technology capable of modifying the surface of existing biomaterials and medical devices through the non-covalent binding of modular biofunctional peptides. These peptides contain at least one material binding sequence and at least one biologically active sequence and thus are termed, "Interfacial Biomaterials" (IFBMs). IFBMs can simultaneously bind the biomaterial surface while endowing it with desired biological functionalities at the interface between the material and biological realms. We demonstrate the capabilities of model IFBMs to convert native polystyrene, a bioinert surface, into a bioactive surface that can support a range of cell activities. We further distinguish between simple cell attachment with insufficient integrin interactions, which in some cases can adversely impact downstream biology, versus biologically appropriate adhesion, cell spreading, and cell survival mediated by IFBMs. Moreover, we show that we can use the coating technology to create spatially resolved patterns of fluorophores and cells on substrates and that these patterns retain their borders in culture. | 18,929,406 |
Phosphatidylserine externalization in caveolae inhibits Ca2+ efflux through plasma membrane Ca2+-ATPase in ECV304. | It has been evidenced that plasma membrane Ca(2+)-ATPase (PMCA) is localized at caveolae. However, the caveolar function of PMCA in living cells has never been demonstrated. In the present study, PMCA is exclusively localized at caveolae from ECV 304 cells demonstrated by sucrose gradient fractionation and the co-localization of PMCA with caveolin-1 was visualized by confocal microscopy. We found that PMCA is the main mechanism involved in Ca(2+) efflux in ECV 304 cells. Treatment of cells with MbetaCD to disrupt caveolae significantly reduced the Ca(2+) efflux, and the rate of decay is 4.45+/-0.14 min(-1) in the absence of MbetaCD and 1.99+/-0.038 min(-1) in the presence of MbetaCD. Moreover, the replenishment of cholesterol restored the reduction of the PMCA-mediated Ca(2+) efflux in the presence of MbetaCD. Consistent with Ca(2+) efflux in living cells, the activity of the reconstituted PMCA in membranes extracted from cells in vitro was decreased in the presence of MbetaCD. It was found that phosphatidylserine, which is normally in the inner leaflet of plasma membranes and is able to stimulate PMCA was relatively enriched in caveolae. Importantly, the treatment of cells with MbetaCD concomitantly increased the phosphatidylserine externalization. Taken together, our results suggest that activation of PMCA in caveolae is modulated by phosphatidylserine, and phosphatidylserine externalization induced by MbetaCD reduced the interaction of phosphatidylserine with PMCA, subsequently PMCA-mediated Ca(2+) efflux in ECV 304 cells. | 18,929,409 |
Outcomes after breast conservation treatment with radiation in women with prior nonbreast malignancy and subsequent invasive breast carcinoma. | Little information has been reported regarding outcomes after treatment for patients with early-stage invasive breast cancer and a prior nonbreast malignancy. This report analyzes the outcomes in patients with Stage I and II breast cancer after breast conservation treatment (BCT) with a prior nonbreast malignancy. The study cohort comprised 66 women with invasive breast cancer and a prior nonbreast malignancy. All patients were treated with breast conservation surgery followed by definitive breast irradiation between 1978 and 2003. Median ages at diagnosis of invasive breast cancer and prior malignancy were 57 and 50 years, respectively. The median interval between the prior malignancy and breast cancer was 7.0 years. Median and mean follow-up times after BCT were 5.3 and 7.0 years. The 5-year and 10-year overall survival rates were 94% (95% confidence interval [CI], 82-98%) and 78% (95% CI, 59-89%), respectively. There were 4 patients (6%) with local failure and 10 patients (15%) with distant metastases. The 10-year rate of local failure rate was 5% (95% CI, 2-16%) and freedom from distant metastases was 78% (95% CI, 61-88%). No obvious differences in survival or local control were noted compared with the reported results in the literature for patients with invasive breast cancer alone. Both overall survival and local control at 5 and 10 years were comparable to rates observed in early-stage breast cancer patients without a prior malignancy. Prior nonbreast malignancy is not a contraindication to BCT, if the primary cancer is effectively controlled. | 18,929,447 |
Effects of caloric restriction on inflammatory periodontal disease. | Dietary caloric restriction (CR) has been found to reduce systemic markers of inflammation and may attenuate the effects of chronic inflammatory conditions. The purpose of this study was to examine the effects of long-term CR on naturally occurring chronic inflammatory periodontal disease in a nonhuman primate model. The effects of long-term CR on extent and severity of naturally occurring chronic periodontal disease, local inflammatory and immune responses, and periodontal microbiology, were evaluated in a cohort of 81 (35 female and 46 male; 13-40 y of age) rhesus monkeys (Macaca mulatta) with no previous exposure to routine oral hygiene. CR monkeys had been subjected to 30% CR for 13-17 y relative to control-fed (CON) animals starting at 3-5 y of age. Same sex CR and CON monkeys exhibited similar levels of plaque, calculus, and bleeding on probing. Among CON animals, males showed significantly greater periodontal breakdown, as reflected by higher mean clinical attachment level and periodontal probing depth scores, than females. CR males exhibited significantly less periodontal pocketing, lower IgG antibody response, and lower IL-8 and ss-glucuronidase levels compared to CON males, whereas CR females showed a lower IgG antibody response but comparable clinical parameters and inflammatory marker levels relative to CON females. Long-term CR had no demonstrable effect on the periodontal microbiota. Males demonstrated greater risk for naturally occurring periodontal disease than females. Long-term CR may differentially reduce the production of local inflammatory mediators and risk for inflammatory periodontal disease among males but not females. | 18,929,461 |
mTOR signaling: RAG GTPases transmit the amino acid signal. | mTOR (mammalian target of rapamycin) is a highly conserved nutrient-responsive regulator of cell growth that is found in all eukaryotes. The mechanism by which amino acids signal to mTOR has remained one of the largest outstanding questions in the field. Two recent complimentary studies provide compelling evidence that the Rag family of small GTPases is both necessary and sufficient to transmit a positive signal from amino acids to mTOR. | 18,929,489 |
Complexes of low energy beta emitters 47Sc and 177Lu with zoledronic acid for bone pain therapy. | Targeted radiopharmaceuticals have been mostly developed to visualize and/or treat oncologic diseases. In targeted radiotherapy radionuclide selection is a key issue, because the radionuclide should provide the appropriate radiation absorbed dose, matching the desirable biologic effect, but at the same time it should preclude irradiation of surrounding healthy tissues. Among the last generation of bisphosphonates with cyclic side chains, zoledronic acid is the most potent bisphosphonate, described till now, which inhibits bone resorption. In this paper, we describe the synthesis, properties and hydroxyapatite binding of zoledronic acid labeled with two low energy beta emitters, (47)Sc and (177)Lu. Radiochemicals labeled with low energy electron emitters are preferred, because they deliver both a therapeutic dose to the bone and spare the bone marrow. Hydroxyapatite adsorption experiments have shown that the binding values obtained with complexes of zoledronic acid labeled with (46)Sc and (177)Lu are much higher than those of bisphosphonates labeled with (153)Sm and (166)Ho. Hence, complexes of zoledronic acid with either (46)Sc or (177)Lu seems to be a promising radiopharmaceutical for bone pain therapy. | 18,929,490 |
Levels and patterns of HIV RNA viral load in untreated pregnant women. | To assess pregnancy levels and patterns of HIV RNA in the absence of antiretroviral therapy, while appropriately adjusting for potential confounders, including maternal immune status and race. Data on > or = 1 antenatal HIV RNA measurements were available for 333 untreated HIV-infected pregnant women enrolled in the European Collaborative Study. CD4 counts and HIV RNA measurements were routinely collected from 1992 and 1998, respectively. Linear mixed effects models based on 246 women for whom complete data were available examined changes in HIV RNA levels over pregnancy, with a nested random effects term accounting for measurement variability within women and period of sample collection. The change in HIV RNA over pregnancy varied significantly by race (p=0.005): from the second trimester until delivery, HIV RNA decreased significantly by an estimated 0.019 log(10) copies/ml/week in white women (95% CI -0.03, -0.007); in black women the estimated 0.016 log(10) copies/ml/week increase (95% CI -0.005, 0.037) was not statistically significant. At delivery, HIV RNA levels in black women were 0.45 log(10) copies/ml higher (95% CI 0.08, 0.83) than in white women. Our findings suggest that HIV RNA dynamics over pregnancy differ by race, although other interpretations cannot be excluded, due to potential for unmeasured confounding. | 18,929,501 |
Use of albumin fusion technology to prolong the half-life of recombinant factor VIIa. | A significant proportion of patients with haemophilia A develop inhibitors to administered factor VIII (FVIII) and require therapy with bypassing agents such as activated factor VII (FVIIa) or activated prothrombin complex concentrates. NovoSeven is a commercially available recombinant FVIIa (rFVIIa) with a very short half-life of approximately 2.4 hours. As a result, patients generally require multiple, frequent infusions for the management of bleeding episodes. Thus, there is growing interest in extending the circulating half-life of coagulation factors through the use of innovative drug delivery and formulation technologies. One such approach uses albumin fusion technology in which human albumin is genetically fused to the C-terminus of rFVIIa via a flexible glycine serine linker. The properties of this rFVIIa fusion protein (rVIIa-FP) have recently been examined in pre-clinical studies. Results from these investigations demonstrate the feasibility of this approach, which successfully extended the half-life and biological activity of rFVIIa without compromising haemostatic efficacy. These data suggest that rVIIa-FP may be a promising therapy for the treatment of haemophilia patients with inhibitors and warrants further investigation in clinical trials. | 18,929,521 |
An international comparability study on quantification of total methyl cytosine content. | Various methods have been developed for quantitative analysis of DNA methylation. However, there is currently no reference analysis system regarding DNA methylation with which other analytical approaches can be compared and evaluated. A standard measurement system that includes reference methods and reference materials may improve comparability and credibility of data obtained from different analytical environments. In an effort to establish a standard system for measurement of DNA methylation, the Korea Research Institute of Standards and Science (KRISS) coordinated an international comparison study among different national metrology institutes. An initial stage of the study involved an intercomparison regarding quantitative measurement of total methyl cytosine contents in artificially constructed DNA samples. The measurement principle involved measurement of dNMP contents following enzymatic hydrolysis of DNA samples. Results of the study showed good comparability among four of five participants and close agreement with reference values assigned by the coordinating laboratory. Conflicting data from one participant may have resulted from incomplete hydrolysis of samples due to use of insufficient amounts of enzymes. These results indicate that comparable and accurate results can be obtained from different measurement environments if digestion conditions are controlled appropriately and valid calibration systems are employed. | 18,929,528 |
Protein aggregates as depots for the release of biologically active compounds. | Protein misfolding and aggregation is one of the most serious problems in cell biology, molecular medicine, and biotechnology. Misfolded proteins interact with each other or with other proteins in non-productive or damaging ways. However, a new paradigm arises that protein aggregation may be exploited by nature to perform specific functions in different biological contexts. From this consideration, acceleration of stress-induced protein aggregation triggered by any factor resulting in the formation of soluble aggregates may have paradoxical positive consequences. Here, we suggest that amorphous aggregates can act as a source for the release of biologically active proteins after removal of stress conditions. To address this concept, we investigated the kinetics of thermal aggregation in vitro of yeast alcohol dehydrogenase (ADH) as a model substrate in the presence of two amphiphilic peptides: Arg-Phe or Ala-Phe-Lys. Using dynamic light scattering (DLS) and turbidimetry, we have demonstrated that under mild stress conditions the concentration-dependent acceleration of ADH aggregation by these peptides results in formation of large but soluble complexes of proteins prone to refolding. | 18,929,533 |
Geranylgeranyl transferase type II inhibition prevents myeloma bone disease. | Geranylgeranyl transferase II (GGTase II) is an enzyme that plays a key role in the isoprenylation of proteins. 3-PEHPC, a novel GGTase II inhibitor, blocks bone resorption and induces myeloma cell apoptosis in vitro. Its effect on bone resorption and tumor growth in vivo is unknown. We investigated the effect of 3-PEHPC on tumor burden and bone disease in the 5T2MM model of multiple myeloma in vivo. 3-PEHPC significantly reduced osteoclast numbers and osteoclast surface. 3-PEHPC prevented the bone loss and the development of osteolytic bone lesions induced by 5T2MM myeloma cells. Treatment with 3-PEHPC also significantly reduced myeloma burden in bone. The magnitude of response was similar to that seen with the bisphosphonate, risedronate. These data show that targeting GGTase II with 3-PEHPC can prevent osteolytic bone disease and reduce tumor burden in vivo, and represents a novel approach to treating tumors that grow in bone. | 18,929,536 |
Point of care testing: transcutaneous bilirubinometry in neonates. | Physicians taking care of infants in the first days of life are often faced with neonatal jaundice, especially in an era where post-partum discharge occurs earlier and assessment of newborn bilirubinemia status is required prior to discharge. The Canadian Pediatric Society and the American Academy of Pediatrics have developed and published guidelines for the diagnosis and management of hyperbilirubinemia in newborns. Point of care testing refers to any test performed outside of laboratory by clinical personnel and close to the site of patient care. Based on a summary of multiple reports during the last twenty years, we realize that devices which provide a non-invasive transcutaneous bilirubin (TcB) measurement have proven to be very useful as screening tools and provide a valid estimate of the total serum bilirubin level (TSB). Published data suggest that these devices provide measurements within 30-50 micromol/L of the TSB levels and can replace laboratory measurement particularly when TSB levels are less than 260 micromol/L. At the present time, in the literature, evidence is insufficient to abandon neonatal serum bilirubin testing and replace it with TcB. Any measurement, TSB or TcB, has potential for error. However, we have evidence that TcB, can help avoiding potential errors associated with even visual assessment of jaundice and may be useful as screening device to detect significant jaundice and decrease a large number of unnecessary skin punctures. The current manuscript is based on a careful comprehensive literature review concerning neonatal hyperbilirubinemia. We consider that this manuscript will help clinicians and laboratory professionals in the management of neonatal jaundice. | 18,929,553 |
The embryonic midbrain directs neuronal specification of embryonic stem cells at early stages of differentiation. | Specific neuronal differentiation of Embryonic Stem Cells (ESCs) depends on their capacity to interpret environmental cues. At present, it is not clear at which stage of differentiation ESCs become competent to produce multiple neuronal lineages in response to the niche of the embryonic brain. To unfold the developmental potential of ESC-derived precursors, we transplanted these cells into the embryonic midbrain explants, where neurogenesis occurs as in normal midbrain development. Using this experimental design, we show that the transition from ESCs to Embryoid Body (EB) precursors is necessary to differentiate into Lmx1a(+)/Ptx3(+)/TH(+) dopaminergic neurons around the ventral midline of the midbrain. In addition, EB cells placed at other dorsal-ventral levels of the midbrain give rise to Nkx6.1(+) red nucleus (RN) neurons, Nkx2.2(+) ventral interneurons and Pax7(+) dorsal neurons at the correct positions. Notably, differentiation of ESCs into Neural Precursor Cells (NPCs) prior to transplantation markedly reduces specification at the Lmx1a, Nkx6.1 and Pax7 expression domains, without affecting neuronal differentiation. Finally, exposure to Fgf8 and Shh in vitro promotes commitment of some ESC-derived NPCs to differentiate into putative Lmx1a(+) dopaminergic neurons in the midbrain. Our data demonstrate intrinsic developmental potential differences among ESC-derived precursor populations. | 18,929,554 |
Proposal for a new tapeworm order, Rhinebothriidea. | The polyphyletic nature of the tapeworm order Tetraphyllidea Carus, 1863 is addressed in part with the establishment of the new order Rhinebothriidea for a subset of the taxa formerly comprising the phyllobothriid subfamily Rhinebothriinae (Platyhelminthes: Eucestoda). Support for the order comes from Bayesian, maximum likelihood, and parsimony analyses of complete ssrDNA and partial (D1-D3) lsrDNA sequence data for 58 cestode species. These data consisted of novel data generated for 40 species in 15 genera of candidate rhinebothriines and the cathetocephalidean species Sanguilevator yearsleyi as well as comparable data taken from GenBank for an additional 18 cestode species in 17 genera. In total, the species analyzed consisted of two Cathetocephalidea, two Litobothriidea, two Lecanicephalidea, three Proteocephalidea, and 49 Tetraphyllidea. The tetraphyllideans consisted of three Onchobothriidae, three Serendipidae, and 43 Phyllobothriidae (one Thysanocephalinae, one Echeneibothriinae, five Phyllobothriinae, 35 candidate Rhinebothriinae and the poorly known Spongiobothrium). This work suggests that some elements of current membership in the group are in need of revision. For example, while inclusion of the echeneibothriine genus Echeneibothrium and the phyllobothriine genera Rhodobothrium and Anthocephalum, and also Spongiobothrium, in the Rhinebothriidea is supported, inclusion of Duplicibothrium and Caulobothrium in the new order is not. Histological sections and scanning electron microscopy of selected members of the study group suggest that the presence of bothridial stalks may serve as an effective morphological feature to characterise the order. The group is restricted to elasmobranchs, and appears to have a particular affinity for Myliobatiformes. The new order includes at least 13 genera. Intraordinal relationships were determined to be insufficiently stable to justify the formal reorganization of rhinebothriidean families at this time. | 18,929,566 |
PICOT is a critical regulator of cardiac hypertrophy and cardiomyocyte contractility. | PICOT (PKC-interacting cousin of thioredoxin) was previously shown to inhibit the development of cardiac hypertrophy, concomitant with an increase in cardiomyocyte contractility. To explore the physiological function of PICOT in the hearts, we generated a PICOT-deficient mouse line by using a gene trap approach. PICOT(-/-) mice were embryonic lethal indicating that PICOT plays an essential role during embryogenesis, whereas PICOT(+/-) mice were viable with no apparent morphological defects. The PICOT protein levels were reduced by about 50% in the hearts of PICOT(+/-) mice. Significantly exacerbated cardiac hypertrophy was induced by pressure overload in PICOT(+/-) mice relative to that seen in wild type littermates. In line with this observation, calcineurin-NFAT signaling was greatly enhanced by pressure overload in the hearts of PICOT(+/-) mice. Cardiomyocytes from PICOT(+/-) mice exhibited significantly reduced contractility, which may be due in part to hypophosphorylation of phospholamban and reduced SERCA activity. These data indicate that the precise PICOT protein level significantly affects the process of cardiac hypertrophy and cardiomyocyte contractility. We suggest that PICOT plays as a critical negative regulator of cardiac hypertrophy and a positive inotropic regulator. | 18,929,570 |
Anti-oligomeric Abeta single-chain variable domain antibody blocks Abeta-induced toxicity against human neuroblastoma cells. | The Amyloid-beta (Abeta) peptide is a major component of the amyloid plaques associated with Alzheimer's disease (AD). Recent studies suggest that the most toxic forms of Abeta are small, soluble oligomeric aggregates. Here, we report the isolation and characterization of a single-chain variable domain (scFv) antibody isolated against oligomeric Abeta using a protocol developed in our laboratory that combines phage display technology and atomic force microscopy (AFM). Starting with a randomized, single framework phage display library, after three rounds of selection against oligomeric Abeta, we identified an scFv that bound oligomeric Abeta specifically, but not monomeric or fibrillar forms. The anti-oligomeric scFv inhibits Abeta aggregation and toxicity, and reduces the toxicity of preformed oligomeric Abeta towards human neuroblastoma cells. When used to probe samples of human brain tissue, the scFv reacted with AD tissue but not a healthy control or Parkinson's disease brain samples. The anti-oligomeric Abeta scFv therefore has potential therapeutic and diagnostic applications in specifically targeting or identifying the toxic morphologies of Abeta in AD brains. | 18,929,576 |
UV but not X rays stimulate homologous recombination between sister chromatids and homologs in a Saccharomyces cerevisiae mec1 (ATR) hypomorphic mutant. | MEC1, the essential yeast ATM/ATR homolog, prevents replication fork collapse and is required for the cellular response to DNA damage. We had previously observed higher rates of spontaneous SCE, heteroallelic recombination and translocations in mec1-21 mutants, which still retain some G2 checkpoint function, compared to mec1 null mutants, which are completely defective in checkpoint function, and wild type. However, the types of DNA lesions that are more recombinogenic in mec1-21, compared to wild type, are unknown. Here, we measured DNA damage-associated SCE, homolog (heteroallelic) recombination, and homology-directed translocations in mec1-21, and characterized types of DNA damage-associated chromosomal rearrangements that occur in mec1-21. Although frequencies of UV-associated recombination were higher in mec1-21, the mutant was defective in double-strand break-associated SCE and heteroallelic recombination. Over-expression of Rad53 in mec1-21 reduced UV-associated recombination but did not suppress the defect in X-ray-associated recombination. Both X ray and UV exposure increased translocation frequencies in mec1-21, but the majority of the UV-associated products were non-reciprocal translocations. We suggest that although recombinational repair of double-stand breaks is less efficient in mec1 mutants, recombinants may be generated by other mechanisms, such as break-induced replication. | 18,929,581 |
Visual deficits in pre-readers at familial risk for dyslexia. | Visual processing deficits in dyslexic readers are argued to evolve as a consequence of reading failure. This study examines dorsal stream functioning of children before they commence formal reading instruction to determine whether visual deficits precede reading difficulties. Coherent motion and visual frequency doubling detection were measured in children at familial risk for dyslexia and in children unselected for family reading history. Here we show that children who are at family risk for dyslexia demonstrate dorsal stream deficits before they learn to read, whilst demonstrating no corresponding deficits in coherent form and static grating control tasks. Results indicate that the dorsal visual deficits observed in dyslexic readers are unlikely to be the result of reading failure. | 18,929,591 |
Deficiency and supplementation of PUFA in the diet have similar effects on the age-associated changes in rat-plasma cholesterol levels. | Levels of plasma cholesterol, particularly LDL cholesterol, increase with increasing age in humans and rodents. Feeding a fish oil-rich diet may exert hypocholesterolemic effects. The aim of this work was to examine the effects of a life-long administration of a PUFA-enriched diet and of a PUFA-deficient diet in male Sprague-Dawley rats on the age-associated increases in plasma cholesterol and triglycerides. Diet had small effects on body-weight, and had dramatic effects on liver phospholipids-fatty acids. Surprisingly, both diets counteracted the age-associated changes in plasma cholesterol and triglycerides similarly and benefits were already visible in adult rats. | 18,929,595 |
Rubus chlorotic mottle virus, a new sobemovirus infecting raspberry and bramble. | The complete nucleotide sequence of a new member of the unassigned genus Sobemovirus, isolated from raspberry and bramble plants in north east Scotland and given the name Rubus chlorotic mottle virus (RuCMV), was obtained. The virus has a single, positive-strand RNA genome of 3,983 nucleotides and, in common with other sobemoviruses, contains four open reading frames (ORFs) encoding, from 5' to 3', the P1 protein that is likely to be a suppressor of RNA silencing, ORF2a that has homology to serine-proteases, ORF2b that is the probable RNA dependent RNA polymerase, and ORF3 that is the coat protein. ORF2b protein is potentially expressed as a fusion with ORF2a protein by a -1 frameshift at the heptanucleotide sequence UUUAAAC. Phylogenetic analyses showed that RuCMV is a distinct virus not closely related to any of the other sequenced sobemoviruses. Based on the obtained sequence a full-length cDNA copy of RuCMV was cloned and in vitro transcripts derived from this clone were shown to be fully infectious. | 18,929,604 |
Tissue differences in the modulation of rat cytochromes P450 and phase II conjugation systems by dietary doses of phenethyl isothiocyanate. | Rats were fed diets supplemented with phenethyl isothiocyanate (PEITC) at 0.06 (low dose, dietary intake level), 0.6 (medium dose) and 6.0 micromole/g (high dose), and xenobiotic-metabolising enzymes were monitored in liver, lung and kidney. At the low dose, inhibition of the hepatic O-dealkylation of ethoxy- and methoxyresorufin was noted, whereas at the high dose increases in the O-depentylation of pentoxyresorufin and O-debenzylation of benzyloxyquinoline were observed, whereas p-nitrophenol hydroxylase was inhibited. Hepatic bioactivation of 2-amino-3-methylimidazo-[4,5-f]quinoline to mutagens was not influenced by the PEITC-treatment. In the lung, at the high dose, ethoxyresorufin dealkylation was elevated and that of pentoxyresorufin suppressed; no significant changes were seen in the kidney. Quinone reductase was markedly elevated at all doses in liver, but the lung enzyme was refractive whereas in the kidney a modest rise was observed at the high dose. Hepatic glutathione S-transferase activity was stimulated by PEITC-treatment, but no effect was evident in the lung or kidney. It is concluded that the effects of PEITC on xenobiotic-metabolising systems are dose- and tissue-dependent, with the liver being the most sensitive and the lung generally resistant. Increased detoxication rather than cytochrome P450 inhibition is the likely mechanism of the chemopreventive activity of PEITC. | 18,929,617 |
Progesterone and progestins: neuroprotection and myelin repair. | Progesterone, known for its role in pregnancy, also exerts marked effects on the nervous system. Its neuroprotective and promyelinating actions, now well documented by experimental studies, make it a particularly promising therapeutic agent for neuroinjury and neurodegenerative diseases. This concept has recently been translated into clinical practice, though there is need for more experimental studies and investigations on the mechanisms of the actions of progesterone. However, it is important to be aware that most of the experimental research concerns the effects of physiological progesterone. Although progesterone represents an interesting therapeutic option, the recognition of its beneficial effects on the nervous system also suggests novel therapeutic benefits for some synthetic progestins derived from progesterone, currently used for contraception or in postmenopausal hormone replacement therapies (HRTs). | 18,929,681 |
Gastrin, Helicobacter pylori, and colorectal adenomas. | Hypergastrinemia and Helicobacter pylori (Hp) infection have been associated with an increased risk for colorectal neoplasia in some studies. However, data from large prospective studies of both associations are lacking. The aim of this study was to evaluate whether serum gastrin levels and/or infection with Hp are associated with the subsequent development of colorectal adenomas. Subjects (all with a history of adenoma formation) were drawn from 2 previously completed adenoma chemoprevention trials. Participants underwent clearing colonoscopy at baseline with follow-up colonoscopy 1 and 4 years after enrollment. We used commercially available assays on fasting blood specimens to measure serum gastrin levels and Hp serologies 1 year after randomization. Risk ratios for adenoma and advanced adenoma development during the subsequent 3 years were computed by generalized linear regression. Of the 1794 subjects randomized in the 2 trials, 685 had available serum and were included in the analyses. Gastrin levels were significantly higher in the 239 subjects with Hp titers indicating infection (mean, 88.3 pg/mL) than in those not infected (mean, 73.9 pg/mL; P < .001). In fully adjusted models, gastrin levels were not associated with incident adenoma development (risk ratio [RR], 1.10; 95% confidence interval [CI], 0.78-1.54) or advanced adenoma formation (RR, 0.82; 95% CI, 0.33-2.03). A positive Hp serology was associated with a decreased risk for adenoma formation (RR, 0.76; 95% CI, 0.60-0.96). Neither hypergastrinemia nor serologic evidence of Hp infection were associated with an increased risk for recurrent adenoma development. These results do not support the notion that gastrin promotes colorectal carcinogenesis, at least at the stage of adenoma development. | 18,929,688 |
Comparison of peripheral arterial response to mental stress in men versus women with coronary artery disease. | There are profound gender-related differences in the incidence, presentation, and outcomes of coronary artery disease (CAD). These differences are not entirely explained by traditional cardiovascular risk factors. Nontraditional risk factors, such as psychological traits, have increasingly been recognized as important contributors to the genesis and outcomes of CAD. Mental stress induces significant peripheral arterial vasoconstriction, with consequent increases in heart rate and blood pressure. These changes are thought to underlie the development of myocardial ischemia and other mental stress-induced adverse cardiac events in patients with CAD. This study examined for gender-related differences in peripheral arterial response to mental stress in a cohort of patients with CAD using a novel peripheral arterial tonometric (PAT) technique. There were 211 patients (77 women; 37%) with a documented history of CAD and a mean age of 64 +/- 9 years. Patients were enrolled from August 18, 2004, to February 21, 2007. Mental stress was induced using a public speaking task. Hemodynamic and PAT measurements were recorded during rest and mental stress. The PAT response was calculated as a ratio of pulse wave amplitude during stress to at rest. PAT responses were compared between men and women. The PAT ratio (during stress to at rest) was significantly higher in women compared with men. Mean PAT ratio was 0.80 +/- 0.72 in women compared with 0.59 +/- 0.48 in men (p = 0.032). This finding remained significant after controlling for possible confounding factors (p = 0.037). In conclusion, peripheral vasoconstrictive response to mental stress was more pronounced in men compared with women. This finding may suggest that men have higher susceptibility to mental stress-related adverse effects. Additional studies are needed to determine the significance of this finding. | 18,929,695 |
Pleiotropic effect of lovastatin, with and without cholestyramine, in the post coronary artery bypass graft (Post CABG) trial. | This study evaluated patients in the Post Coronary Artery Bypass Graft (Post CABG) trial for evidence of statin pleiotropic effects in preventing atherosclerotic progression in saphenous vein grafts (SVGs). We studied 1,116 of the 1,351 patients in the Post CABG trial who were randomized to aggressive (low-density lipoprotein [LDL] cholesterol target <85 mg/dl) or moderate (target LDL cholesterol <140 mg/dl) lovastatin treatment and who had sufficient data available. The generalized estimating equation models, adjusting for important covariates, were applied to estimate the odds ratios (ORs) and probability of substantial atherosclerotic SVG progression (decrease in lumen diameter >or=0.6 mm) and the difference in minimum lumen diameter change between treatment groups. Aggressive lovastatin treatment compared with moderate treatment was associated with a significant decrease in risk of significant SVG atherosclerotic progression after adjustment for baseline cholesterol level, LDL cholesterol on treatment, high-density lipoprotein cholesterol, and triglyceride changes on treatment and other independent predictors (OR 0.68, 95% confidence interval 0.49 to 0.94, p = 0.019). Results were similar when the change or percent change from baseline of LDL cholesterol level on treatment was adjusted for rather than on-treatment LDL cholesterol and in the subset achieving a year-1 LDL cholesterol level from 90 to 135 mg/dl (OR 0.64, 95% confidence interval 0.42 to 0.98, p = 0.042). Mean decrease in minimum lumen diameter was also significantly smaller in the aggressive than the moderate treatment arm (-0.256 vs -0.343 mm, p = 0.042). In conclusion, aggressive versus moderate lovastatin treatment appeared therapeutic in slowing the atherosclerotic process in SVGs from Post CABG patients, independent of its greater LDL cholesterol-lowering effect. | 18,929,703 |
Predicting effects of exercise training in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. | The purpose of this study was to investigate which patient characteristics may predict training effects on maximal and submaximal exercise performance in patients with heart failure. Together with commonly used clinical and performance-related variables, oxygen uptake kinetics during exercise recovery were included as possible predictors. Fifty patients with heart failure (New York Heart Association class II or III) performed a 12-week training program (cycle interval and resistance training). Training effects were expressed as changes in peak oxygen uptake (Vo(2)), Vo(2) at ventilatory threshold (VT), and the time constant of Vo(2) recovery after submaximal exercise (tau-rec). After training, peak Vo(2), Vo(2) at VT, and tau-rec improved significantly, with a wide variety in training responses. Changes in peak Vo(2) were related to changes in VT (r = 0.79, p <0.001), but both changes were not related to changes in tau-rec. Using multivariate regression analyses, post-training changes in peak Vo(2) could be predicted by recovery halftime of peak Vo(2) (T1/2), peak Vo(2) (percentage of predicted), and peak respiratory exchange ratio (R(2) = 36%). Post-training changes in VT could be predicted by T1/2 and VT (predicted) (R(2) = 29%), whereas changes in tau-rec could be predicted only by tau-rec at baseline (R(2) = 34%). In conclusion, oxygen recovery kinetics after maximal and submaximal exercise substantially add to the prediction of training effects in patients with heart failure, presumably because of their relations with, respectively, central and peripheral impairments of exercise capacity. However, the explained variance in training effects is not sufficient to make a definite distinction between training responders and nonresponders. | 18,929,712 |
[Salter and Harris type-II distal femoral physeal fracture-separations at adolescent age: a new therapeutic approach (preliminary study)]. | The prognosis of distal femoral physeal fracture-separation is poor in children. In adolescents, more than half of the cases are classified as Salter and Harris type-II. The gold-standard treatment for a displaced fracture combines anatomic reduction with internal fixation with a pin or screw, preserving the growth cartilage. Despite this treatment, the rate of mid- and long-term complications has been high in the literature, most problems being related to leg length discrepancy and misalignments (genu valgum and genu varum). In order to avoid these problems, for adolescents, we propose and osteosynthesis system which bridges the entire growth cartilage with a blade-plate. Depending on the bone age, puberty and thus potential for further growth, we combine this osteosynthesis with a contralateral distal femoral epiphysiodesis to prevent invalidating leg length discrepancy. We reviewed retrospectively the cases of 21 patients aged 11 to 15 years treated between 1990 and 2005 for Salter and Harris type-II distal femoral physeal fracture- separation. Clinical and radiographic outcome was compared between the 16 patients treated with the classical internal fixation system or cast immobilization and the five patients treated with a blade-plate. A complete physical examination was available for the follow-up in all cases. A full stance view was used for the radiographic analysis. The mean follow-up was 6.7 years (range 2-17), minimal two years. In patients treated with the classical fixation system or a plaster cast, four of 16 (25 %) developed frontal misalignment of more than 5 degrees and five of 16 (32 %) leg length discrepancy of more than 2cm. No misalignment or leg length discrepancy (>2cm) was observed among the five patients treated with a blade-plate. The results observed in our patients treated with the classical fixation systems are comparable with those reported by others. Our patients treated with the blade-plate system constitute the only series with no cases of frontal misalignment or invalidating leg length discrepancy after this type of fracture. We used contralateral distal femoral epiphysiodesis in all patients whose predictable leg length discrepancy at the end of growth was greater than 2cm, that is 11-3.5 years (bone age) in girls and 13-14.5 years in boys. Internal fixation techniques bridging the growth cartilage are the only techniques used for Salter and Harris type-II distal femoral physeal fracture-separation in adolescents which have been able to prevent posttraumatic knee misalignment (genu valgum or genu varum). Leg length discrepancy can be prevented by a contalateral distal femoral epiphysiodesis when the fracture occurs in a child or early puberty. | 18,929,748 |
Usefulness of TC-99M GSA liver scintigraphy for the evaluation of liver regeneration in donors after living-donor liver transplantation. | We evaluated the impact of steatosis on regeneration and function of the remnant liver by using technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy. Twelve living donors were classified into groups with or without mild hepatic steatosis according to the liver-to-spleen attenuation ratio on computed tomography: six donors had a ratio > or = 1.2 (control group) and six had a ratio < 1.20 (fatty liver group). Scintigraphy was performed to determine the hepatic uptake ratio of the tracer (corrected for disappearance from the blood) and the maximum removal rate of the tracer by hepatocytes as parameters of the hepatic functional reserve. The fatty liver group had a significantly lower corrected hepatic uptake ratio and removal rate compared with the control group at 6 and 12 months after partial hepatectomy. The regenerated liver volume estimated by scintigraphy did not differ significantly between the two groups at any time. Because donors with mild hepatic steatosis showed impaired liver regeneration at 1 year after partial hepatectomy, management of these donors requires more care. | 18,929,767 |
Preoperative vascular evaluation in living donor liver transplantation for biliary atresia. | Liver transplantation is an important treatment option in the management of end-stage liver disease. Preoperative vascular evaluation plays an important role for a safe and successful operation, especially in pediatric patients undergoing living donor liver transplantation (LDLT). The purpose of this study is to assess the usefulness and accuracy of Doppler ultrasound (US), computed tomographic angiography (CTA), and magnetic resonance angiography (MRA) in evaluating vascular anomalies in patients with biliary atresia (BA) undergoing LDLT. Images of Doppler US, CTA, and MRA for preoperative vascular evaluation in 55 patients with BA undergoing LDLT were reviewed with the operative findings. All patients underwent preoperative US, CTA, and MRA. Pathologic portal vein (n = 18), interruption of the retrohepatic vena cava (n = 1), and aberrant right hepatic artery from the superior mesenteric artery (n = 2) were confirmed during the transplantation. The success rates of CTA and MRA in identifying vascular anomalies were 96% and 82%, respectively (P = .01). The sensitivity, specificity, and accuracy of Doppler US were 89%, 94%, and 92%, respectively. For CTA, it was 94%, 97%, and 96%, respectively; for MRA (including technical failure), it was 75%, 97%, and 89%, respectively. Doppler US serves as an initial assessment for vascular evaluation and has the advantage in determining vascular flow quantities. CTA and MRA are used for precise surgical planning. However, MRA has lower success and accuracy rates when compared with CTA (P = .01). Doppler US with CTA can provide accurate preoperative vascular imaging in patients with BA undergoing LDLT. | 18,929,771 |
Retransplantation for end-stage liver disease: a single-center Asian experience. | Liver retransplantation carries a significantly higher morbidity and mortality compared with patients after single transplantations. The aim of this study was to review our outcomes in liver retransplantations. From February 1984 to February 2007, 409 liver transplantations were performed on 396 patients, including 13 retransplantations (3.2%) in 12 patients. The mean follow-up was 1.6 +/- 0.4 years (range, 0.1-5.2). The mean duration between the first and the second transplantation was 2.8 +/- 1.0 years (range, 15 days-11.6 years). The indications for the first liver transplantation included biliary atresia (n = 3), hepatitis B virus (HBV)-related cirrhosis with hepatoma (n = 3), fulminant hepatic failure (n = 2), HBV-related end-stage liver disease (n = 1), hepatitis C virus (HCV)-related end-stage liver disease (n = 1), neonatal hepatitis (n = 1), and glycogen storage disease (n = 1). The indications for retransplantations were secondary biliary cirrhosis (n = 3), veno-occlusive disease-related liver failure (n = 2), hepatic arterial occlusion and graft failure (n = 2), chronic rejection with hepatic graft failure (n = 2), recurrent HBV (n = 1) and de novo HBV-related decompensated cirrhosis (n = 1), and idiopathic graft failure (n = 1). There were 4 living donor and 9 deceased donor liver retransplantations. The cumulative survival rate was 71.4 +/- 14.4%, with an estimated mean survival time of 3.9 +/- 0.7 years. Our results showed that minimizing the rate of retransplantation was critical to enhance overall patient survival. Moreover, living donor liver retransplantation is another option within the short, yet critical, waiting period, after failure of the first graft. Provided that a suitable living donor is available, we recommend early retransplantation to minimize the risk of morbidity and mortality. | 18,929,780 |
Peroneal neuropathy after liver transplantation. | The incidence of peroneal neuropathy (PN), occurring predominantly in the left leg, increases after the incorporation of intermittent pneumatic compression (IPC) devices among adult liver transplantation (OLT) recipients in our hospital. The aim of this study was to investigate the possible risk factors for PN and the reason for the left-leg predominance. We retrospectively reviewed the medical records of 501 OLT recipients. The patients were first divided into 2 groups, PN (n = 33) and non-PN (n = 468), to assess possible risk factors. The patients were then categorized into IPC (n = 262) and non-IPC (n = 239) groups according to the use of IPC devices. In a subsequent prospective study, we measured the degree and duration of the tilt of the operating table during OLT to investigate their relationship to the predominant left-leg PN. The rate of IPC device use was significantly greater among the PN than non-PN group (78.8% vs 50.4%, P < .01). The incidence of PN was significantly higher among the IPC than non-IPC group (9.9% vs 2.9%, P < .01). The degree and duration of left tilt of the operating table were greater and longer than the right tilt. The use of IPC devices during OLT increased the occurrence of PN and the left tilt of the operating table was strongly related to the predominant left-leg PN. Careful protection of the vulnerable point and minimization of the tilting of the operating table is advised during OLT, especially when IPC devices are used. | 18,929,798 |
Successful islet transplantation from the pancreata of non-heart-beating donors. | We performed 6 islet transplantations in 4 type 1 diabetes mellitus patients. From September 2003 to April 2007, 23 islet isolations were performed from pancreata of non-heart-beating donors. The pancreata preserved using a 2-layer method or simple cold storage in University of Wisconsin solution were transferred to our cell processing center. The islet isolation was performed according to the Edmonton protocol with some modifications. The immunosuppressive protocol was achieved using sirolimus, tacrolimus, and anti-CD25 antibody (basiliximab). Islet yield was 400 to 491,040 IEQ and purity was 1% to 70%. Stimulation indices upon static incubation were 1.38 to 11.69. All patients who underwent islet transplantation showed positive serum C-peptide levels immediately after transplantation. Although insulin independence was not achieved, they displayed stabilized blood glucose levels, reduced insulin doses, and disappearance of hypoglycemic unawareness. Although stomatitis and diarrhea due to the side effects of sirolimus were observed in 2 patients, there were no severe complications. In patient 1, serum C-peptide levels decreased gradually from 1 year after transplantation. In conclusion, successful islet transplantation was possible using islets isolated from the pancreata of non-heart-beating donors. Further improvements are needed to achieve prolonged graft survival. | 18,929,803 |
Experimental microencapsulation of porcine and rat pancreatic islet cells with air-driven droplet generator and alginate. | Transplantation of microencapsulated islets is proposed as an ideal therapy for the treatment of type 1 diabetes mellitus without immunosuppression. This strategy is based on the principle that foreign cells are protected from the host immune system by an artificial membrane. The aim of this study was to establish an ideal condition of microencapsulation using an air-driven droplet generator and alginate in vitro. The optimal conditions for islet encapsulation were an alginate inflow rate of 10 mL/h, CO2 flow rate of 2.0 L/min in a concentration of 2% alginate. For 2.5% alginate, the alginate inflow rate of 20 mL/h, CO2 flow rate 3.0 L/min was ideal; alginate inflow rate of 40 mL/h, CO2 flow rate of 4.0 L/min showed good microcapsules at 3% alginate. Viability of encapsulated islets was greater than 90%. In terms of insulin secretion, encapsulated islets secreted insulin in response to glucose in static culture medium. However, there was no normal response to low or high glucose challenge with a stimulation index less than 2.0. Microencapsulation of pig islets was successfully performed with air-driven droplet generator and alginate in vitro. Further studies about biocompatibility and glucose control in vivo may provide a useful tool for treatment of patients with diabetes mellitus. | 18,929,806 |
Glutamine induces heat-shock protein-70 and glutathione expression and attenuates ischemic damage in rat islets. | The transplantation of isolated islets is believed to be an attractive approach for cure of diabetes mellitus. Heat-shock protein (HSP70), which plays a vital role in cellular protection, has been detected in various tissues subjected to stress. Glutamine (GLN) is an important cellular fuel and an essential precursor for the antioxidant glutathione (GSH). It is believed to enhance cellular survival against a variety of stressful stimuli through HSP70. Thus, we performed this study to examine the hypothesis that preoperative GLN administration induces HSP70 and GSH expression before islet transplantation attenuating ischemic damage to rat islets. Adult male Sprague-Dawley (SD) rats were randomly divided into two groups according to the administration of GLN after islet isolation. Group A served as the controls, receiving no GLN. Group B islet cells were cultured with L-GLN (10 mmol/L) supplementation for 24 hours. The GSH levels were measured in islet cells. Both HSP70 and proteins related to apoptosis were analyzed in islet cells by Western blots. Isolated rat islets were cultured with interleukin (IL)-1beta. Nitrite production was measured using the Griess reagent. The GSH levels were significantly elevated in the glutamine-treated group. HSP70 expression in islets treated with GLN was markedly stronger compared with the control group. The basal Bcl-2 expression was markedly increased by GLN treatment. The GLN-treated group showed attenuated IL-1beta-induced injury in association with NO production. These results suggested that preoperative GLN administration induced HSP70 and GSH expressions before islet transplantation, thus attenuating IL-1beta-induced injury in association with NO production and apoptosis, which might be potential tool to mitigate the ischemic damage to islet cells and the early inflammation at the site of implantation through a self-protective mechanism. | 18,929,807 |
Heart transplantation 1987--2007: 20 years' experience at Chulalongkorn hospital. | After many years, heart transplantation is still the most accepted treatment for end-stage heart disease. A heart transplantation program was started at our hospital in December 1987 as the first intrathoracic organ transplantation in Southeast Asia. Herein, we have reviewed our 20 years of experience from 1987 to 2007. We followed every individual within our 52-patient cohort for up to 20 years. Three eras were studied: 1987 to 1995, 1996 to 2002, and 2003 to 2007. End points were survival, rejection, infection event, and graft coronary artery disease (CAD). There were 52 patients (39 males and 12 females). The mean age was 41.7 years (range, 12-23 years). Perioperative mortality (within 1 month) was 13.4% (n = 7) due to graft failure (n = 2), rejection (n = 3), infection (n = 1), on pulmonary hypertension (n = 1). Medium-term mortality (1-12 months) was 30.7% (n = 16) due to rejection (n = 8), infection (n = 7), or CAD (n = 1). After 1 year causes of death were rejection (n = 4), infection (n = 4), renal failure (n = 2), or CAD (n = 1). Overall actuarial 1-, 5-, and 10-year survival rates for all recipients were 54.7%, 43.3%, and 32.5%, respectively. The first patient in this series is still alive. For the period 2003 to 2007, actuarial 1-year and 4-year survival rates for all recipients were both 77.8%. The rate of rejection was reduced to just one event during this period. All surviving patients were NYHA Functional class I and II; 86% went back to work, leading almost normal lives. Improved survival in the current era may be attributed to better organ preservation, improved immunosuppression, and control of infection, as well as less graft CAD. Those who survive more than 1 year have a good quality of life. | 18,929,809 |
Heart transplantation under cyclosporine or tacrolimus combined with mycophenolate mofetil or everolimus. | In this study, we examined whether cyclosporine was effective when combined with everolimus in clinical heart transplantation (HT). From August 2004 to July 2007, 108 adult patients underwent primary HT. The main exclusion criteria were: donors > 60 years; cold ischemia times > 6 hours; recipients of multiorgan transplantation or a previous transplantation; and panel-reactive antibodies > or = 25%. The cyclosporine plus everolimus regimen (group CE, n = 32) was suggested first; upon refusal or if the recipient or donor was positive for hepatitis B surface antigen or PCR + hepatitis C infection, then patient was randomly assigned to success cyclosporine plus mycophenolate mofetil (MMF; group CM, n = 24) or tacrolimus plus MMF (group TM, n = 25). All patients underwent similar operative procedures and postoperative care with protocol endomyocardial biopsies. No 30-day mortality was noted in any group. The efficacy failure rates were 3%, 25%, and 16% in groups CE, CM, and TM, respectively (P = .04 between groups CE and CM). The 1-year survivals were 96.7% +/- 18.1%, 89.7% +/- 29.8%, and 81.0% +/- 35.5% for groups CE, CM, and TM, respectively (P = .04 between groups CE and TM). The 3-year survival rates were 91.9% +/- 28.3%, 79.8% +/- 46.0%, and 81.0% +/- 35.5% in groups CE, CM, and TM, respectively. The 3 immunosuppressive regimens offered good efficacy after HT. The cyclosporine plus everolimus regimen showed a significantly better result with less efficacy failure (compared with cyclosporine plus MMF: 3% vs 25%) and better 1-year survival compared with tacrolimus plus MMF: 96.7% vs 81.0%. | 18,929,814 |
The upregulation of osteoblast marker genes in mesenchymal stem cells prove the osteoinductivity of hydroxyapatite/tricalcium phosphate biomaterial. | Calcium phosphate (Ca-P), mainly concerning hydroxyapatite (HA), is the main inorganic component of the body's hard tissue. It is acknowledged that Ca-P biomaterial not only has osteoconduction but also can form bone bonding to host bone, making an ideal tissue-engineering scaffold. However, whether Ca-P biomaterial possesses osteoinductivity is still debated. The present study was performed to explore the expression level of osteoblast maker genes in human mesenchymal stem cells (hMSCs) grown on a Ca-P biomaterial. hMSCs were cultured on the HA/tricalcium phosphate-(TCP) double-phase ceramic. After coculture for 5, 10, 15, or 20 days, the cells were digested for isolation of total RNA. Fluorescence quantitative polymerase chain reaction was used to detect the relative mRNA levels of Runx2, collagen type I, osteopontin, and osteocalcin, all of which are the marker genes for osteoblasts. The mg63 cell was recruited as the reference and un-cocultured hMSCs as the negative controls. Alkaline phosphatase (ALP) activity in the cells was also examined after culture for 10 or 20 days. Our results showed that the expression levels of all four genes continued to rise during the first 10 days. Then, both collagen type I and Runx2 decreased. In contrast, osteocalcin mRNA reached its maximum at day 15 and osteopontin mRNA kept increasing throughout the whole experimental period. Additionally, ALP activity increased in a time-dependent manner. The up-regulation of all four osteoblast marker genes in hMSCs grown on Ca-P biomaterial suggested that HA/TCP biomaterials possess osteoinductivity on hMSCs, cells a mechanism that requires further investigation. | 18,929,827 |
Irradiation is an early determinant of endothelial injury during hematopoietic stem cell transplantation. | We investigated the degree and the time course of endothelial injury in mice pretreated with lethal or reduced-intensity irradiation administered before transplantation. Six- to eight-week-old female mice were randomly allocated into three groups: lethal-intensity irradiation (8.5 Gy, group 1), reduced-intensity irradiation (5.0 Gy, group 2), or nonirradiated controls (group 3). After conditioning, circulating endothelial cells (CD31+, CD133(-), and CD45low) and peripheral blood CD4+ or CD8+ T-lymphocyte subpopulations were enumerated using flow cytometry at various times. The morphologic changes in endothelium were examined at phase-contrast light microscopy. Circulating endothelial cells showed an earlier and higher peak in the lethal irradiation group compared with the reduced-intensity irradiation group, which exhibited a protean elevation in cell numbers. There were no visible histopathologic changes during the early stage of endothelial damage. Lethal and reduced doses of irradiation induced endothelial injury in a dose-dependent manner. Endothelial damage may occur before graft-vs-host disease and its related complications. | 18,929,830 |
Relationship between TH1/TH2 cytokines and immune tolerance in liver transplantation in rats. | To explore the relationship between Th1/Th2 cytokine expressions and immune tolerance in rat liver transplantation. Recipients were divided into three groups (each group = 12 rats). The allograft group underwent orthotopic liver transplantation from male Wistar-to-Sprague-Dawley (SD) rats. The isograft group of SD-to-SD liver transplantation was complemented with a control group of normal male SD rats that had sham operations. We evaluated the 2-week survival rates histological changes, as well as serum and mRNA expression levels of Th1/Th2 cytokines: interferon-gamma (IFN-gamma) and interleukin-10 (IL-10). The 1-week survival in the isograft and allograft groups were 100% and 41.67%, respectively. The 2-week survival rates were 75% and 8.33% (P < .05). Light microscopic inspection revealed severe acute rejection in the allograft but not the isograft group in the first week postoperation. This observation was verified by the cellular morphology under transmission electron microscopy. Serum IFN-gamma (Th1 cytokine) levels (pg/mL) determined by enzyme-linked immunosorbent assay in the allograft, isograft, and control groups were 386.67 +/- 14.36, 159.83 +/- 16.53, and 87.83 +/- 8.67, respectively; for IL-10 (Th2 cytokine), they were 126.33 +/- 13.10, 288.33 +/- 17.10, and 70.50 +/- 7.23, respectively (P < .05, allograft vs isograft). The semiquantitative reverse-transcriptase polymerase chain reaction assay showed that expression of IFN-gamma and IL-10 mRNA was similar to that of serum levels. IFN-gamma mRNA was more highly expressed in the allograft group and IL-10 mRNA, in the isograft group (P < .05). The dynamic equilibrium of Th1/Th2 cytokines is critically involved in immune tolerance. The deviation of Th1 to Th2 may be one mechanism of immune tolerance. | 18,929,837 |
Induction of indoleamine 2,3-dioxygenase in livers following hepatectomy prolongs survival of allogeneic hepatocytes after transplantation. | Indoleamine 2,3-dioxygenase (IDO), which catalyzes the breakdown of tryptophan into kyneurenine, has immunologic significance for the induction of maternal tolerance and liver allograft tolerance by inhibiting T-cell activation. In the present study, we compared survival of syngeneic or allogeneic hepatocytes in livers with or without hepatectomy. Subsequently, we investigated gene expression and localization of IDO in the recipient liver. DA and Fisher 344 rats were used in the following experimental groups: group 1, DA hepatocytes transplanted into hepatectomized Fisher 344 rats; group 2, Fisher 344 hepatocytes transplanted into hepatectomized Fisher 344 rats; group 3, DA hepatocytes transplanted into nonhepatectomized Fisher 344 rats; and group 4, Fisher 344 hepatocytes transplanted into nonhepatectomized Fisher 344 rats. After transplantation, the surviving cells were evaluated on day 5. The IDO signal of the recipient liver was detected by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. In the hepatectomized groups subjected to allogeneic or syngeneic hepatocyte transplantation, the number of surviving hepatocytes was greater than in the nonhepatectomized group after transplantation. The IDO signals (RT-PCR) in the hepatectomized groups were stronger than those in the nonhepatectomized groups. Immunohistochemistry demonstrated that the IDO signal is located in liver antigen-presenting cells, such as Kupffer cells or dendritic cells, and not expressed in hepatocytes. Our results demonstrated that IDO is induced in antigen-presenting cells of hepatectomized livers by which subsequently transplanted cells may be protected from rejection by inhibiting indirect or direct recognition of donor antigen and further T-cell activation. | 18,929,841 |
Rapamycin-induced cytotoxic signal transduction pathway. | We examined the effects of rapamycin on activation, proliferation, and expression of cytotoxic effector molecules in Molt-4 human T lymphocytes. We investigated the effects of rapamycin on cell viability, caspase family protein activities. Western blots of Bcl-2, Bak, p53, p21, p27, Rb, CDK2, and cyclin B1, as well as measurement of reactive oxygen species (ROS) generation and mitochondrial membrane potential transition. Cells were cultured in the presence or absence of rapamycin. Flow cytometric analysis was performed using propidium iodide stain. Viability of Molt-4 cells was decreased by the addition of rapamycin in dose- and time-dependent manners. Rapamycin induced no nuclear fragmentation in Molt-4 cells. Generation of H2O2 in rapamycin-treated Molt-4 cells increased in a time-dependent manner. There were no changes among catalytic activities of caspase proteases. And there was no evidence of expression of Bcl-2, p53, p21, p27, or Rb proteins. G2/M phase cell cycle arrest was identified by flow cytometry. We noted decreased expressions of CDK2 and cyclin B1. We also noted increased Bak protein expression and change in mitochondrial membrane potential transition. In conclusion, rapamycin-induced cytotoxicity was characterized by generation of ROS, which modulated Bak protein expression and mitochondrial dysfunction. G2/M phase cell cycle arrest was achieved by decreased expressions of CDK2 and cyclin B1. | 18,929,849 |
Cloning, sequencing, and analysis of the full-length CDNA of rhesus monkey factor IX. | Coagulation factor IX (FIX) is a vitamin K-dependent serine protease, which plays a key role in the coagulation cascade. The rhesus monkey may be an indispensable substitute for humans in research of pig-to-human xenotransplantation, due to its close relationship. But the coagulation function concordance between rhesus monkey and human is unknown. In this study, we cloned the full-length cDNA of rhesus monkey FIX (rFIX) to investigate the genomic backgrounds of the coagulation systems. We cloned the full-length cDNA from the cDNA library of rhesus monkey liver tissue. Polymerase chain reaction was used to screen the positive clones. Based on a partial sequence obtained by cDNA library screening and a homologous sequence from the database, we designed a second pair of primers to obtain the full sequence. For further analysis of rFIX, we used several online ExPASy Proteomic tools. We obtained the full-length cDNA of rFIX, which has 2668 nucleotides, predicting an open reading frame of 1383 nucleotides corresponding to 461 amino acids. The deduced protein sequence indicated functional domains of signal peptide, Gla, two epidermal growth factor, and trypsin-like serine protease, which were consisted with those of human FIX (hFIX). Sequence alignments showed that rFIX is highly homologous to hFIX with nucleotide identity of 96% and amino acid identity of 97%. We have report herein the full-length cDNA of rFIX. The high homology between rhesus monkey and human coagulation factor ensure the reliability and feasibility of rhesus monkey as a recipient in studies on coagulation disorders in xenotransplantation. | 18,929,857 |
Molecular cloning of pig Rad51, Rad52, and Rad54 genes, which are involved in homologous recombination machinery. | The low rate of homologous recombination in somatic cells is considered to be an urgent issue. Therefore, we molecularly cloned three genes that relate to efficient homologous recombination. Polymerase chain reaction (PCR) was performed to isolate candidate cDNA fragments from a pig spleen cDNA library with the corresponding primer sets deduced from multiple alignment analysis of other mammalian genes. A 5'- and 3'-RACE PCR experiment was performed to determine the complete cDNA sequences. The complete cDNA sequences of the pig RAD51, RAD52, and RAD54 genes, which are closely related to homologous recombination events, were identified using molecular cloning technique. The cDNA sequences of three genes were successfully isolated by PCR-based methods. As a result, we determined the sequences of pig RAD51 (1663 bp, 339 aa), RAD52 (1884 bp, 406 aa), and RAD54 (2884 bp, 747 aa). The nucleic acid sequence homologies of the pig RAD51, RAD52, and RAD54 genes compared with the corresponding human genes were 92.9%, 77.3%, and 90.0%; the corresponding amino acid sequence homologies were 98.8%, 71.1%, and 95.0%, respectively. The knockout of alpha-1,3-galactosyltransferase in pigs resulted in a drastic reduction in xenoantigenicity. However, other xenoantigens, in particular, the non-Gal antigens, also need to be down-regulated. Gene transfer to alter expression levels of these recombination-related molecules and/or ex ante evaluation of expression profiles of these genes in primary cultures of somatic cells constitute a new approach to enhancing homologous recombination events during the production of gene knockout pigs. | 18,929,859 |
[Lymphomatoid papulosis in childhood: six case reports and a literature review]. | Lymphomatoid papulosis (LyP) is a rare lymphoproliferative disorder. It is now included in the World Health Organisation (WHO) classification of cutaneous lymphomas. Although frequently described in adults, there have been only a few reported cases of LyP in children; diagnosis is often difficult in this population and no clear guidelines have been established regarding management or monitoring. In this article we report six new cases of LyP in children. This is a retrospective study of six children, aged between two and 11 years, seen at the Hôtel-Dieu Hospital in Lyon and at the Grenoble Hospital Centre between 2005 and 2008. Each child underwent skin biopsy for histological and immunohistochemical analysis. All six children presented papulonodular lesions on the limbs and trunk, in some cases necrotic, present for different times and developing in episodes. Histology and immunolabelling announces in all six cases militated in favour of LyP type A, with large CD30+ and CD15- cells dispersed in an inflammatory dermal infiltrate made up for the most part of lymphocytes, polynuclear neutrophils, eosinophils and a small number of histiocytes. Only around 60 cases of LyP have so far been reported in children, principally type A. Association with malignant lymphoma occurs, with high risk in relation to the general population of the same age. Clinical diagnosis is confirmed histopathology and immunolabelling. There is currently no consensus regarding therapeutic management. First-line treatment generally comprises therapeutic abstention or dermal corticosteroids. Methotrexate and phototherapy constitute possible alternatives but should be used only in very disseminate or debilitating forms of the disease. The presentation and course of LyP of childhood differs very little from the adult form. Cases of associated lymphoma have been reported. Although regular clinical monitoring is recommended, there is no call for routine laboratory testing. | 18,929,914 |
Building human resilience: the role of public health preparedness and response as an adaptation to climate change. | Global climate change will increase the probability of extreme weather events, including heatwaves, drought, wildfire, cyclones, and heavy precipitation that could cause floods and landslides. Such events create significant public health needs that can exceed local capacity to respond, resulting in excess morbidity or mortality and in the declaration of disasters. Human vulnerability to any disaster is a complex phenomenon with social, economic, health, and cultural dimensions. Vulnerability to natural disasters has two sides: the degree of exposure to dangerous hazards (susceptibility) and the capacity to cope with or recover from disaster consequences (resilience). Vulnerability reduction programs reduce susceptibility and increase resilience. Susceptibility to disasters is reduced largely by prevention and mitigation of emergencies. Emergency preparedness and response and recovery activities--including those that address climate change--increase disaster resilience. Because adaptation must occur at the community level, local public health agencies are uniquely placed to build human resilience to climate-related disasters. This article discusses the role of public health in reducing human vulnerability to climate change within the context of select examples for emergency preparedness and response. | 18,929,977 |
The chronic care model and relationships to patient health status and health-related quality of life. | The chronic care model (CCM) is a system-level framework used to guide quality improvement efforts in health care. However, little is known about its relationship to patient-level health measures. This study describes the implementation of the CCM as adapted for prevention and health behavior counseling in primary care practices, and examines relationships between the CCM and patient health measures, including general health status and health-related quality of life (HRQOL). Baseline data from Round 2 of the Prescription for Health initiative (2005-2007) were used to assess CCM implementation in 57 practices located nationwide. Relationships between the CCM and three separate measures of health among 4735 patients were analyzed in 2007. A hierarchical generalized linear modeling approach to ordinal regression was used to estimate categories of general health status, unhealthy days, and activity-limiting days, adjusting for patient covariates and clustering effects. Outcome variances were significantly accounted for by differences in practice characteristics (p<0.001). Practices that used individual or group planned visits were more likely to see patients in lower health categories across all measures (OR=0.74-0.81, p<0.05). Practices that used patient registries, health promotion champions, evidence-based guidelines, publicly reported performance measures, and support for behavior change were associated with higher patient health levels (OR=1.28-1.98, p<0.05). A practice's implementation of the CCM was significantly related to patient health status and HRQOL. Adapting the CCM for prevention may serve to reorient care delivery toward more proactive behavior change and improvements in patient health outcomes. | 18,929,987 |
Intravascular papillary endothelial hyperplasia: report of 2 cases and immunohistochemical study. | Intravascular papillary endothelial hyperplasia (IPEH) is a benign, nonneoplastic, vascular lesion. The main significance of the lesion lies in the fact that it may be mistaken for angiosarcoma. Oral lesions are uncommon and the present paper reports 2 cases of oral IPEH, in different sites. Histologically, the tissue was characterized by papillary fronds lined by proliferating endothelium. Immunohistochemically (IHC), the lesion was positive for CD34, smooth muscle actin (SMA), type I and IV collagen, vimentin, and laminin, but it was negative for CD105. Local excision was the treatment of choice. No recurrence was observed during a 1-year and 6-month follow-up period, respectively. The clinical, histological, and immunohistochemical characteristics are discussed. | 18,929,993 |
Efficient bioethanol production from xylose by recombinant saccharomyces cerevisiae requires high activity of xylose reductase and moderate xylulokinase activity. | We varied the promoter strength of xylose reductase (XR) gene and the copy number of xylulokinase (XK) gene to determine how XR and XK activities affect the xylose-fermenting abilities of recombinant Saccharomyces cerevisiae expressing xylitol dehydrogenase (XDH). The most enhanced ethanol yield and lowered xylitol yield occurred in strain I-PGK/AUR, which has high activity of both XR and XDH and moderate XK activity. | 18,930,011 |
Detailed molecular dynamics simulations of model biological membranes containing cholesterol. | Detailed molecular dynamics simulations performed to study the nature of lipid raft domains that appear in model membranes are reviewed in this paper. The described simulations were performed on hydrated bilayers containing binary mixtures of cholesterol with phospholipids and also on ternary mixtures containing cholesterol, a phospholipid with a high main transition temperature T(m), and a phospholipid with a low transition temperature T(m). These simulations provide qualitative and semi-quantitative information about cholesterol-lipid interactions and also a testing ground for major assumptions made to explain the nature of lipid rafts in model membranes. | 18,930,019 |
Expression profiling of chicken DT40 lymphoma cells indicates clonal selection of knockout and gene reconstituted cells. | The DT40 cell-line has been extensively used to create deletion mutants, one of which lacks Bruton's tyrosine kinase (Btk). Btk is a cytoplasmic tyrosine kinase important for B-lymphocyte maturation. It was previously shown that there are differences in gene expression between wild-type and Btk-deficient animals. Global gene expression profiling of the avian B-lymphoma DT40 cell-line was used as a model to differentiate among Btk knockout (KO) and Btk KO cells reconstituted with human Btk. Differences in the gene expression pattern showed statistically significant changes between parental DT40 and all the Btk KO cell populations irrespective of whether they are reconstituted or not. These results imply that in the process of generating a knockout cell-line, sub-clones are selected, which have multiple changes in their gene expression pattern (p<0.01). Although other parameters could also influence the expression profile, this potentially has important implications when interpreting microarray data from gene-deleted cell-lines. | 18,930,021 |
Trafficking and function of the tetraspanin CD63. | Tetraspanins comprise a large superfamily of cell surface-associated membrane proteins characterized by four transmembrane domains. They participate in a variety of cellular processes, like cell activation, adhesion, differentiation and tumour invasion. At the cell surface, tetraspanins form networks with a wide diversity of proteins called tetraspanin-enriched microdomains (TEMs). CD63 was the first characterized tetraspanin. In addition to its presence in TEMs, CD63 is also abundantly present in late endosomes and lysosomes. CD63 at the cell surface is endocytosed via a clathrin-dependent pathway, although recent studies suggest the involvement of other pathways as well and we here present evidence for a role of caveolae in CD63 endocytosis. In late endosomes, CD63 is enriched on the intraluminal vesicles, which by specialized cells are secreted as exosomes through fusion of endosomes with the plasma membrane. The complex localization pattern of CD63 suggests that its intracellular trafficking and distribution must be tightly regulated. In this review we discuss the latest insights in CD63 trafficking and its emerging function as a transport regulator of its interaction partners. Finally, the involvement of CD63 in cancer will be discussed. | 18,930,046 |
Effect of cell-penetrating peptides on the nasal absorption of insulin. | The goal of this study was to evaluate whether cell-penetrating peptides (CPPs) affect the nasal absorption of insulin. L- or D-forms of penetratin, or the L- or D-forms of octaarginine (L- or D-R8), was used as first time for nasal insulin delivery. Furthermore, the concentration of lactate dehydrogenase (LDH) in nasal lavage fluid was determined and a histopathological study of nasal respiratory epithelium was conducted. CPPs dramatically increased nasal insulin absorption, and it was more pronounced for L- and D-penetratin than L- or D-R8. L-penetratin was the most effective promoter of insulin absorption compared with others CPPs. A dose-dependent relationship of L-penetratin and insulin bioavailability was statically significant. The pharmacological availability and bioavailability of nasally administered insulin was up to 76.7% and 50.7% relative to the subcutaneous route, respectively. In contrast, increasing the D-penetratin concentration decreased the efficiency of nasal insulin absorption. There was no significant difference in the release of LDH in nasal lavage fluid and the integrity of nasal respiratory epithelium when L-penetratin was present. In conclusion, these data demonstrate that L-penetratin markedly increased the permeability of insulin across the nasal membrane without causing detectable damage to the integrity of cells in the nasal respiratory mucosa. | 18,930,084 |
Effective and safe immunizations with live-attenuated vaccines for children after living donor liver transplantation. | Immunizations using live-attenuated vaccines are not recommended for post-liver transplant children due to its theoretical risks. However, they will encounter vaccine-preventable viral diseases upon returning to real-life situations. We performed a total of 70 immunizations with four individual live-attenuated vaccines to 18 pediatric post-living donor liver transplant (LDLT) recipients who fulfilled a clinical criteria including humoral and cell-mediated immunity. The seroconversion rates at the first dose for measles (strain AIK-C), rubella (strain TO-336), varicella (strain Oka), and mumps (strains Hoshino) were 100% (15/15), 100% (15/15), 82% (9/11), and 82% (9/11), respectively. During observed period (-5 years 11 months), a few cases with waning immunity (antibodies were once produced but the levels fell over time) were seen except after rubella immunization. Clinical diseases after seroconversion or definite serious adverse effects due to immunization were not observed. Immunizations using selected live-attenuated vaccines were safe and effective for post-LDLT children who were not severely immunosuppressed. | 18,930,096 |
Levofloxacin rescues mice from lethal intra-nasal infections with virulent Francisella tularensis and induces immunity and production of protective antibody. | The ability to protect mice against respiratory infections with virulent Francisella tularensis has been problematic and the role of antibody-versus-cell-mediated immunity controversial. In this study, we tested the hypothesis that protective immunity can develop in mice that were given antibiotic therapy following infection via the respiratory tract with F. tularensis SCHU S4. We show that mice infected with a lethal dose of SCHU S4, via an intra-nasal challenge, could be protected with levofloxacin treatment. This protection was evident even when levofloxacin treatment was delayed 72h post-infection. At early time points after levofloxacin treatment, significant numbers of bacteria could be recovered from the lungs and spleens of mice, which was followed by a dramatic disappearance of bacteria from these tissues. Mice successfully treated with levofloxacin were later shown to be almost completely resistant to re-challenge with SCHU S4 by the intra-nasal route. Serum antibody appeared to play an important role in this immunity. Normal mice, when given sera from animals protected by levofloxacin treatment, were solidly protected from a lethal intra-nasal challenge with SCHU S4. The protective antiserum contained high titers of SCHU S4-specific IgG2a, indicating that a strong Th1 response was induced following levofloxacin treatment. Thus, this study describes a potentially valuable animal model for furthering our understanding of respiratory tularemia and provides suggestive evidence that antibody can protect against respiratory infections with virulent F. tularensis. | 18,930,100 |
Natural feed additive of Macleaya cordata: safety assessment in rats a 90-day feeding experiment. | Macleaya cordata (Willd.) (Papaveraceae) is used as an active component in the natural feed additive Sangrovit. Sangrovit contains mixture of the intact aerial parts and the fraction of quaternary benzo[c]phenanthridine alkaloids from M. cordata (FQBA). In a 90-day pilot toxicity trial, Sangrovit and the FQBA were tested for safety. Male Wistar rats were fed for 90 days with 100, 7000 or 14000mg of Sangrovit or 600mg of FQBA in 1kg of feed. Body and organ weights, clinical chemistry and hematology markers, oxidative stress parameters, morphological structure of tongue, liver, ileum, kidney and heart samples, and total cytochrome P450 in liver were monitored. The results showed no statistically significant alterations in any parameter between control and treated animals, except for the group treated with 14000ppm Sangrovit that resulted in elevation of reduced glutathione level and superoxide dismutase activity in liver. | 18,930,108 |
In vivo comparison of epithelial responses for S-8 versus JP-8 jet fuels below permissible exposure limit. | This study was designed to characterize and compare the pulmonary effects in distal lung from a low-level exposure to jet propellant-8 fuel (JP-8) and a new synthetic-8 fuel (S-8). It is hypothesized that both fuels have different airway epithelial deposition and responses. Consequently, male C57BL/6 mice were nose-only exposed to S-8 and JP-8 at average concentrations of 53mg/m(3) for 1h/day for 7 days. A pulmonary function test performed 24h after the final exposure indicated that there was a significant increase in expiratory lung resistance in the S-8 mice, whereas JP-8 mice had significant increases in both inspiratory and expiratory lung resistance compared to control values. Neither significant S-8 nor JP-8 respiratory permeability changes were observed compared to controls, suggesting no loss of epithelial barrier integrity. Morphological examination and morphometric analysis of airway tissue demonstrated that both fuels showed different patterns of targeted epithelial cells: bronchioles in S-8 and alveoli/terminal bronchioles in JP-8. Collectively, our data suggest that both fuels may have partially different deposition patterns, which may possibly contribute to specific different adverse effects in lung ventilatory function. | 18,930,109 |
Complex actions of thyroid hormone receptor antagonist NH-3 on gene promoters in different cell lines. | It is desirable to obtain new antagonists for thyroid hormone receptors (TRs) and other nuclear receptors (NRs). We previously used X-ray structural models of TR ligand binding domains (LBDs) to design compounds, such as NH-3, that impair coactivator binding to activation function 2 (AF-2) and block thyroid hormone (triiodothyronine, T(3)) actions. However, TRs bind DNA and are transcriptionally active without ligand. Thus, NH-3 could modulate TR activity via effects on other coregulator interaction surfaces, such as activation function (AF-1) and corepressor binding sites. Here, we find that NH-3 blocks TR-LBD interactions with coactivators and corepressors and also inhibits activities of AF-1 and AF-2 in transfections. While NH-3 lacks detectable agonist activity at T(3)-activated genes in GC pituitary cells it nevertheless activates spot 14 (S14) in HTC liver cells with the latter effect accompanied by enhanced histone H4 acetylation and coactivator recruitment at the S14 promoter. Surprisingly, T(3) promotes corepressor recruitment to target promoters. NH-3 effects vary; we observe transient recruitment of N-CoR to S14 in GC cells and dismissal and rebinding of N-CoR to the same promoter in HTC cells. We propose that NH-3 will generally behave as an antagonist by blocking AF-1 and AF-2 but that complex effects on coregulator recruitment may result in partial/mixed agonist effects that are independent of blockade of T(3) binding in some contexts. These properties could ultimately be utilized in drug design and development of new selective TR modulators. | 18,930,112 |
Facilitation of voluntary swallowing by chemical stimulation of the posterior tongue and pharyngeal region in humans. | In this study, we investigated the functional difference between chemical stimulations of the posterior tongue (PT) and pharyngeal region (PR) for facilitation of voluntary swallowing in humans. The PT or PR stimulation consisted of infusion of water (distilled water), 0.3 M NaCl solution or olive oil (non-chemical stimulant) into the PT or the PR through a fine tube at a very slow infusion rate (0.2 ml/min). Water was used as a stimulant of water receptors. A solution of 0.3 M NaCl was used as an inhibitor of the response of water receptors and as a stimulant of salt taste receptors. Excitation of the mucosal receptors would facilitate voluntary swallowing and diminution of sensory inputs from the oral mucosa would induce difficulty in swallowing. Swallowing intervals (SIs) during voluntary swallowing were measured by submental electromyographic activity. Infusion of water into the PR shortened SI (facilitation of swallowing) and infusion of 0.3 M NaCl or olive oil into the same region prolonged it (difficulty in swallowing). On the other hand, infusion of water into the PT prolonged SI and infusion of 0.3 M NaCl into the same region shortened it. The results suggest that water receptors are localized in the PR and that salt taste receptors are almost absent in the PR and present in the PT. With diminution of sensory inputs from the oral mucosa, central inputs would play a dominant role in initiating swallowing voluntarily, and SI would be prolonged. With weak stimulation (infusion of 0.3 M NaCl into the PR or infusion of water into the PT), SI was prolonged and inter-individual variation in SI was pronounced, suggesting that the ability of the central regulation of swallowing to perform repetitive voluntary swallowing varies among subjects. With stimulation of water receptors or salt taste receptors, SI was shortened and inter-individual variation in SI was moderate, suggesting that sensory inputs are important for performing voluntary swallowing smoothly and that the sensory inputs compensate for the difficulty in performing swallowing caused by the central mechanism. | 18,930,115 |
Human phenotypes associated with GATA-1 mutations. | GATA-1 is one of the six members of the GATA gene family, a group of related transcription factors discovered in the 1980s. In the past few decades, the crucial role of GATA-1 in normal human hematopoiesis has been delineated. As would be expected, mutations in GATA-1 have subsequently been found to have important clinical significance, and are directly linked to deregulated formation of certain blood cell lineages. This paper reviews the functional consequences of GATA-1 mutations by linking specific errors in the gene, or its downstream protein products, to documented human diseases. These five human diseases are: X-linked thrombocytopenia (XLT), X-linked thrombocytopenia with thalassemia (XLTT), congenital erythropoietic porphyria (CEP), transient myeloproliferative disorder (TMD) and acute megarakaryoblastic leukemia (AMKL) associated with Trisomy 21, and, lastly, a particular subtype of anemia associated with the production of GATA-1s, a shortened, mutant isoform of the wild-type GATA-1. The different phenotypic expressions associated with GATA-1 mutations illustrate the integral function of the transcription factor in overall body homeostasis. Furthermore, these direct genotype-phenotype correlations reinforce the importance of unraveling the human genome, as such connections may lead to important therapeutic or preventive therapies. | 18,930,124 |
Integrating genomics across drug discovery and development. | The sequencing of the human genome was an exceptional achievement, but it was not an end in itself as it set the foundation for building new knowledge in biology and medicine. The laborious, multifaceted science of drug discovery and development also draws tremendous benefits from mining the human genome and exploiting the large palette of genomic technologies. This article discusses how diverse genomic tools have been used to date and how they will continue to be utilized in the future to impact drug discovery and development. Integrating genomics across drug discovery and development will undoubtedly help to shorten timelines, increase success rates at all stages and ultimately bring the right drugs to the right patients at the right times. | 18,930,125 |
Formulation and pharmacokinetics of lipid nanoparticles of a chemically sensitive nitrogen mustard derivative: Chlorambucil. | Lipid nanoparticles of the cancer drug Chlorambucil (CLB) were prepared by ultrasonication, using stearic acid as the core lipid. Four types of lipid nanoparticle formulations were studied: (i) stearic acid solid lipid nanoparticles (SLN); (ii) sterically stabilized SLN with pegylated phospholipids as stabilizer; (iii) nanostructured lipid complexes with oleic acid as adjunct lipid; (iv) lipid nanocomplexes with dimethyl dioctadecyl ammonium bromide (DDAB) as surface modifier (LN). Lipid nanoparticles were characterized for particle size, assay and encapsulation efficiency, particle morphology and physico-chemical stability over 90 days. All of the formulations were physically stable, with an average particle size of 147 (+/-10)nm. The drug encapsulation efficiency (DEE) of all the formulations except LN decreased significantly over time (p<0.05), probably due to the expulsion of CLB upon crystallization. This indicated that the presence of DDAB in stearic acid nanoparticles increases DEE, preventing CLB degradation in the aqueous disperse phase. Pharmacokinetic studies of the intravenous LN formulation revealed plasma clearance kinetics were comparable to that of CLB solution (p>0.01), indicating electrostatic charge mediated clearance, as reported earlier. In tissue and tumor distribution studies, lower AUC values of CLB were observed for LN compared to CLB solution in liver, kidneys, heart and lungs. However, higher AUC values of LN formulation as compared to CLB solution (p<0.01) in tumors suggested that the presence of DDAB on the lipid nanoparticles resulted in greater accumulation of the drug in tumors. | 18,930,127 |
A transposon insertion mutant of Mycobacterium fortuitum attenuated in virulence and persistence in a murine infection model that is complemented by Rv3291c of Mycobacterium tuberculosis. | Mycobacterium fortuitum is a non-tubercular fast growing pathogenic mycobacteria whose virulence factors have not been studied. Infection of M. fortuitum ATCC 6841 in a murine infection model leads to spinning of the head in 8-12 days after infection, 20-25% mortality and a constant bacillary load in the kidney of mice, suggesting persistence. From a TnphoA insertion library, a mutant MT13 was isolated which was attenuated in virulence with lesser bacterial burden, milder and delayed spinning of the head and no mortality of mice. The significant feature of the mutant was its failure to persist in kidney and thus the persistent bacillary load characteristic exhibited by the wild type strain was not observed. The insertion of transposon in MT13 was mapped in a region of the genome, which showed homology to Rv3291c of M. tuberculosis, annotated as a transcriptional regulatory factor and reported to be up regulated in nutrient starvation and anaerobic persistent states. Complementation of MT13 with rv3291c resulted in restoration of wild type characteristics including persistence in kidney suggesting the role of a Rv3291c homolog in the virulence and persistence of M. fortuitum. | 18,930,129 |
Minimization of immunosuppression: transplant immunology. | Induction of tolerance, which obviates the need for maintenance immunosuppression following organ transplantation remains elusive. In cardiac transplantation, ongoing immunosuppressive therapy is essential to ensure long-term graft survival. Although drug regimens have substantially improved in recent years, their adverse effects continue to cause significant morbidity and affect quality of life. Newer immunosuppressive therapies have been effective at reducing allograft rejection rates in the short term but long term outcomes have changed little in the last two decades. Minimization of immunosuppression requires appreciation of the potential consequence. High risk patients in particular need to be identified and excluded from low intensity immunosuppressive regimens. A variety options exist for lowering of immunosuppression and steroid weaning has now become common practice with about 40% of all cardiac transplant recipients remaining steroid free in the long term. Minimization of calcineurin inhibitor exposure may be achieved with concurrent use of the more potent anti-proliferative agents mycophenolate mofetil and sirolimus. Patients require close monitoring for rejection during weaning. In addition to the conventional clinical parameters which include therapeutic drug monitoring, endomyocardial biopsy and echocardiography, newer techniques for monitoring hold future promise. These include detection of circulating alloantibodies and quantitative measurement of the net state of immunosuppression (Cylex). However, the efficacy of these modalities requires further investigation. | 18,930,138 |
Identification of mitochondrial disease genes through integrative analysis of multiple datasets. | Determining the genetic factors in a disease is crucial to elucidating its molecular basis. This task is challenging due to a lack of information on gene function. The integration of large-scale functional genomics data has proven to be an effective strategy to prioritize candidate disease genes. Mitochondrial disorders are a prevalent and heterogeneous class of diseases that are particularly amenable to this approach. Here we explain the application of integrative approaches to the identification of mitochondrial disease genes. We first examine various datasets that can be used to evaluate the involvement of each gene in mitochondrial function. The data integration methodology is then described, accompanied by examples of common implementations. Finally, we discuss how gene networks are constructed using integrative techniques and applied to candidate gene prioritization. Relevant public data resources are indicated. This report highlights the success and potential of data integration as well as its applicability to the search for mitochondrial disease genes. | 18,930,150 |
Live cell imaging of phosphoinositides with expressed inositide binding protein domains. | Inositol lipids and calcium signaling has been inseparable twins during the 1980s when the molecular details of phospholipase C-mediated generation of inositol 1,4,5-trisphosphate (InsP3) and its Ca2+ mobilizing action were discovered. Since then, both the Ca2+ and inositol lipid signaling fields have hugely expanded and the tools allowing dissection of the finest details of their molecular organization also followed closely. Although phosphoinositides regulate many cell functions unrelated to Ca2+ signaling there are still many open questions even in the Ca2+ field that would benefit from single cell monitoring of PtdIns(4,5)P2 or InsP3 changes during agonist stimulation. This chapter is designed to provide practical guidance as well as some theoretical background on measurements of phosphoinositides in live cells using protein domain-GFP chimeras that could be also useful for people working on calcium signaling. | 18,930,153 |
Phylogeny and generic limits in the Niemeyera complex of New Caledonian Sapotaceae: evidence of multiple origins of the anisomerous flower. | Traditional generic limits within the "Niemeyera complex" (Sapotaceae: Chrysophylloideae) in Australia and New Caledonia do not correspond to natural groups. We analyzed nuclear (ETS, ITS) and chloroplast (trnH-psbA, trnS-G) sequence data, and 42 morphological characters, using a near-complete taxon sampling. The resulting phylogeny provides a new generic framework where Leptostylis and Sebertia are monophyletic, Niemeyera is recognized as a small genus confined to Australia, and the circumscriptions of Achradotypus and Pycnandra require significant modification. This framework allows about 20 recently discovered species to be described in appropriate genera and assessed for their conservation status. Evolutionary changes in two widely used characters, anisomerous flowers and the number of stamens inserted opposite each corolla lobe, have occurred multiple times. There is no evidence that anisomery originated through hybridization as suggested in other groups. Instead, the two characters are closely coupled and often mutually exclusive. The diagnostic value of morphological characters varies considerably; for example, the presence, absence, and type of malpighiaceous hairs convey more phylogenetic information than many traditionally used features. Criteria and options for a new generic classification are discussed, and a reconstruction of the hypothesized ancestor that likely colonized New Caledonia in the Oligocene is presented. | 18,930,157 |
Characterization of the Aspergillus niger prtT, a unique regulator of extracellular protease encoding genes. | Expression of several Aspergillus niger genes encoding major secreted, but not vacuolar, protease genes including the major acid protease gene pepA, was shown to be affected in the previously isolated A. niger protease mutant, AB1.13 [Mattern, I.E., van Noort, J.M., van den Berg, P., Archer, D.A., Roberts, I.N., Hondel, C.A.M.J.J., 1992. Isolation and characterization of mutants of Aspergillus niger deficient in extracellular proteases. Molecular & General Genetics 2, 332-336]. Complementation cloning of the putative protease-regulatory gene affected in this mutant was accomplished using a functional selection approach based on the use of the A. nidulans amdS selection marker driven by the A. niger pepA promoter. As expected the PpepA::amdS selection marker is not expressed in the mutant. Introduction of a self-replicating cosmid library into the mutant strain carrying the PpepA::amdS marker allowed selection of AmdS+ transformants functionally complementing the proposed regulatory mutation. Analysis of complementing cosmid clones revealed that the complementing sequences contained a gene encoding a member of the fungal-specific Zn2Cys6-binuclear cluster protein family. Sequence comparison of the encoded protein, PrtT, showed that it has homologues among different Aspergillus species. The A. oryzae homologue was shown to govern expression of the major alkaline protease AlpA and neutral protease Np1 in this species. In contrast to several other pathway specific regulators, such as AmyR and XlnR, no PrtT orthologues could be found in any other non-Aspergillus (or related) species and surprisingly, also not in Aspergillus nidulans. Interestingly, in all Aspergillus species carrying a prtT orthologue the gene is tightly clustered to a completely syntenous region carrying an amylolytic gene cluster including another Zn2Cys6-binuclear cluster protein, AmyR. Northern analysis of the A. niger prtT gene showed (constitutive) expression from two upstream promoters about 700 bp apart. The presence of several short upstream open reading frames downstream of both the distal and the proximal transcription start point of the prtT gene suggests regulation at the post-translational level. Also regulation at the level of differential splicing is suggested by the fact that several Aspergillus EST databases carry a considerable fraction of clones in which in frame intron sequences are retained. | 18,930,158 |
Astrocytes as gate-keepers in optic nerve regeneration--a mini-review. | Animals that develop without extra-embryonic membranes (anamniotes--fish, amphibians) have impressive regenerative capacity, even to the extent of replacing entire limbs. In contrast, animals that develop within extra-embryonic membranes (amniotes--reptiles, birds, mammals) have limited capacity for regeneration as adults, particularly in the central nervous system (CNS). Much is known about the process of nerve development in fish and mammals and about regeneration after lesions in the CNS in fish and mammals. Because the retina of the eye and optic nerve are functionally part of the brain and are accessible in fish, frogs, and mice, optic nerve lesion and regeneration (ONR) has been extensively used as a model system for study of CNS nerve regeneration. When the optic nerve of a mouse is severed, the axons leading into the brain degenerate. Initially, the cut end of the axons on the proximal, eye-side of the injury sprout neurites which begin to grow into the lesion. Simultaneously, astrocytes of the optic nerve become activated to initiate wound repair as a first step in reestablishing the structural integrity of the optic nerve. This activation appears to initiate a cascade of molecular signals resulting in apoptotic cell death of the retinal ganglion cells axons of which make up the neural component of the optic nerve; regeneration fails and the injury is permanent. Evidence specifically implicating astrocytes comes from studies showing selective poisoning of astrocytes at the optic nerve lesion, along with activation of a gene whose product blocks apoptosis in retinal ganglion cells, creates conditions favorable to neurites sprouting from the cut proximal stump, growing through the lesion and into the distal portion of the injured nerve, eventually reaching appropriate targets in the brain. In anamniotes, astrocytes ostensibly present no such obstacle since optic nerve regeneration occurs without intervention; however, no systematic study of glial involvement has been done. In fish, vigorously growing neurites sprout from the cut axons and within a few days begin to re-enervate the brain. This review offers a new perspective on the role of glia, particularly astrocytes, as "gate-keepers;" i.e., as being permissive or inhibitory, by comparison between fish and mammals of glial function during ONR. | 18,930,160 |
Development and validation of the patient and clinician sedation satisfaction index for colonoscopy and upper endoscopy. | Recent increases in gastrointestinal endoscopic procedures and sedation options show a need for better sedation evaluation. This article describes the development and validation of 2 instruments: the Patient Satisfaction with Sedation Instrument (PSSI) and the Clinician Satisfaction with Sedation Instrument (CSSI) for assessing satisfaction in patients undergoing outpatient upper endoscopy and colonoscopy. A total of 118 patients who underwent outpatient colonoscopy or esophagogastroduodenoscopy and 22 physicians were recruited across 5 US gastroenterology practices. Physicians completed the CSSI and patients completed the PSSI after each procedure. Patients completed the SF-12 Health Survey, Patient Satisfaction Questionnaire, and Socially Desirable Response Scale; clinicians completed the Observer's Assessment of Alertness Scale after procedures. Study patients were mostly women (59%), white (88%), had a mean age of 57.5 +/- 15.7 years, and had a colonoscopy (70%). Internal consistency reliabilities assessed result consistencies across test items. Coefficients greater than 0.70 indicate good reliability; greater than 0.85 indicate excellent reliability. Internal consistency reliabilities of the PSSI and CSSI total and subscale scores were greater than 0.76. Correlations were assessed using Pearson product moment correlation. PSSI and CSSI scores were correlated (P < .05). PSSI totals scores were correlated significantly with the SF-12 Health Survey (P < .05), the Patient Satisfaction Questionnaire (P < .05), and CSSI total scores were correlated with the Observer's Assessment of Alertness Scale (P < .01) and a visual analogue scale (P < .01). PSSI scores were not correlated with the Socially Desirable Response Scale (P > .05). The PSSI and CSSI provide for feasible, reliable, and valid assessment of procedural sedation satisfaction for outpatient colonoscopy and esophagogastroduodenoscopies and can be used for future sedation studies. | 18,930,167 |
Monitoring particle aggregation processes. | A wide range of test methods for monitoring particle aggregation processes is reviewed. These include techniques for measuring aggregation rates in fundamental studies and those which are useful in the monitoring and control of practical coagulation/flocculation processes. Most emphasis is on optical methods, including light transmission (turbidity) and light scattering measurements and the fundamentals of these phenomena are briefly introduced. It is shown that in some cases, absolute aggregation rates can be derived. However, even when only relative rates can be obtained, these can still be very useful, for instance in defining optimum flocculation conditions. Some of the methods available for investigating properties of aggregates (flocs), such as size, strength and fractal dimension are also discussed, along with some related properties such as sedimentation rate and filterability of flocculated suspensions. | 18,930,173 |
[Stenting or coronary artery bypass surgery for triple vessel disease?]. | This review was undertaken to objectively analyse the cumulated medical literature on techniques of myocardial revascularization (angioplasty, bare metal stenting, drug eluting stenting, coronary artery surgery) in multivessel coronary artery disease. Randomized trials, meta analyses and registries comparing these treatment modalities show a short and long term advantage of surgery over percutaneous techniques for angina recurrence and need for repeat revascularization, although mortality and myocardial infarction rate do not seem statistically different. Diabetes mellitus, chronic renal failure and female gender represent high risk subgroups. Data on drug eluting stents are to date limited to the short term; however, it does not seem that drug eluting stents have resolved the need for repeat revascularization. Stenting addresses focal lesion whereas future revascularization occurs on other coronary sites by progression of coronary disease. Cardiologists should objectively inform the consenting coronary multivessel disease patient on the risk of repeat revascularization inherent to percutaneous techniques and on the weight of actual data favouring surgery in multivessel disease. | 18,930,176 |
CYP17 and CYP19 gene polymorphisms in women affected with endometriosis. | To investigate whether CYP17 T>C polymorphism and polymorphisms C1558T and Val80 of CYP19 are related to endometriosis. Clinical study. Women affected with endometriosis (n = 104) and control group (n = 86). The diagnosis of endometriosis was confirmed by the histologic examination of the endometriotic lesions. In patients affected with endometriosis, we observed that AA and CC genotypes were significantly represented in Val80 and C1558T polymorphisms of CYP19. The molecular mechanisms that underlie the development of endometriosis are unclear. Both environmental and genetic factors are involved in the pathogenesis of the disease. The inheritable susceptibility to endometriosis justifies the growing interest in identifying genes and/or genetic polymorphisms that predispose women to an increased risk of developing endometriosis. The identification of single-nucleotide polymorphism (SNP), probably linked to endometriosis, could help to explain its pathogenesis. | 18,930,188 |
Concentration and distribution of hyaluronic acid in mouse uterus throughout the estrous cycle. | To quantify and study the immunoexpression of hyaluronic acid (HA) in the uterine horns of the mouse throughout the estrous cycle phases. Experimental study using an ELISA-like fluorometric assay to quantify HA and an avidin-biotin immunoperoxidase method using biotinylated hyaluronan-binding protein for histochemical studies. University-based laboratory. Forty regularly cycling adult female mice were divided into four groups according to the diagnosed phase of the cycle: proestrus, estrus, metaestrus, and diestrus. None. Histologic samples of the uterine horns. Immunohistochemical reaction was evaluated by detection of HA and CD44 distribution within the uterine horn. Tissue HA content was determined through an ELISA-like fluorometric assay with the same hyaluronan-binding protein and with europium-labeled streptavidin. The immunohistochemical HA and CD44 reactions were most intense during diestrus, mainly below the luminal epithelium. HA was strongly stained in the connective tissue near the myometrium layer during metaestrus. The biochemical data showed that the highest concentration of HA in uterine horns occurred during diestrus (4053.0 +/- 651.4 ng/g dry tissue) compared with other phases. Our data show that the expression of HA in mouse uterine horns is highest during the diestrous phase. The fluctuations of HA in the mouse uterus during the estrous phase may be related to the varying estrogen and P levels during the cycle and may be important as far as embryo implantation is concerned. | 18,930,192 |
A functional promoter polymorphism in interleukin-10 gene influences susceptibility to endometriosis. | To investigate the involvement of inflammation in the development of endometriosis. Case-control study to investigate the association between endometriosis and four inflammation-related genes: interleukin (IL)-6, IL-10, IL-1 beta, and cyclooxygenase-2. University hospital. We had 196 cases with pathologically proved endometriosis and 397 disease-free women as control subjects. A total of 12 single nucleotide polymorphisms (SNPs) were selected for genotyping, including functional SNPs and common tagging SNPs. Logistic regression and haplotype analyses were performed to evaluate the genetic effect with adjustment for other covariates. Genotypes at each SNP were in Hardy-Weinberg equilibrium in either case or control subjects, except for rs1800871 at IL-10 in the case subjects (P=.04). We found that the individuals carrying minor allele C of a functional promoter SNP rs1800871 at IL-10 was associated with a reduced risk by approximately twofold compared with the common TT genotype. The T allele was reported to have a lower gene expression level than the C allele, suggesting inadequate suppression of inflammation leading to endometriosis development. Haplotype analysis of the IL-10 gene did not yield a better result. Other genes were not associated with endometriosis. This study suggests that the functional promoter polymorphism at IL-10 may play a role in the development of endometriosis. | 18,930,197 |
Preimplantation genetic screening in a case of recurrent trisomy 21 offspring. | To describe a unique case of recurrent aneuploidy and the use of preimplantation genetic screening (PGS). Case report. Midwest academic medical center. A 36-year-old woman with two trisomy 21 offspring. Preimplantation genetic screening. Karyotype of embryos, liveborn eukaryotic infant. Preimplantation genetic screening was performed on three cryopreserved embryos, followed by a two-embryo transfer yielding a eukaryotic infant. Preimplantation genetic screening may prove to be useful as a diagnostic tool to help ensure a euploid pregnancy when termination is not a viable option for a couple. | 18,930,202 |
A combined analysis of data to identify predictive factors for spermatogenesis in men with hypogonadotropic hypogonadism treated with recombinant human follicle-stimulating hormone and human chorionic gonadotropin. | To compare the efficacy and safety of recombinant human FSH (r-hFSH) and hCG treatment for male hypogonadotropic hypogonadism (HH) in different populations and to identify characteristics predictive of spermatogenesis. A combined analysis of data from four clinical trials. Phase III, open-label, noncomparative studies with similar designs conducted in Australia, Europe, Japan, and the United States. One hundred men with complete idiopathic or acquired HH. Pretreatment with hCG for 3-6 months, followed by combination therapy with hCG and r-hFSH (150 IU three times weekly) for up to 18 months. Doses of r-hFSH were adjusted according to spermatozoa count until the maximum dose was reached. The primary efficacy endpoint was a spermatozoa concentration of >or=1.5 x 10(6)/mL. A total of 81 men remained azoospermic but achieved normal serum T concentrations after hCG pretreatment. Of these, 68 (84.0%) achieved spermatogenesis and 56 (69.1%) achieved spermatozoa concentrations >or=1.5 x 10(6)/mL. Large baseline mean testicular volume, low body mass index, and advanced sexual maturity were predictors of good response to therapy. Similar treatment responses were observed across different study populations. R-hFSH (combined with hCG) is effective for the restoration of fertility in the majority of men with HH. | 18,930,225 |
Relationships between measures of fitness, physical activity, body composition and vascular function in children. | The prevalence of obesity and physical inactivity in Western countries has increased rapidly. Both are modifiable risk factors for cardiovascular disease. Atherosclerosis begins in childhood and endothelial dysfunction is its earliest detectable manifestation. We assessed flow-mediated dilation (FMD) in 129 children (75 female; 10.3+0.3 yrs; 54 male; 10.4; 0.3 yrs). FMD was normalised for differences in the eliciting shear rate stimulus between subjects (SR(AUC)). Fitness was assessed as peak oxygen uptake during an incremental treadmill exercise test (V O(2)peak). Body composition was measured using a dual-energy X-ray absorptiometry (DEXA) scan. Physical activity (PA) was assessed using Actigraph accelerometers. The cohort was split into tertiles according to FMD% and also FMD% corrected for SR(AUC) to gain insight into the determinants of vascular function. Across the cohort, significant correlations were observed between FMD%/SR(AUC) and DEXA percentage fat (r=-0.23, p=0.009) and percentage lean mass (r=0.21, p=0.008), and also with PA performed at moderate-to-high intensity (r=0.363, p=0.001). For children in the lowest FMD%/SR(AUC) tertile, a stronger relationship with all PA measures was observed, particularly with high intensity PA (r=0.572, P=0.003). Regression analysis revealed that high intensity PA was the only predictor of impaired FMD%/SR(AUC). These data suggest that traditional risk factors for CHD in adult populations impact upon vascular function in young people. Furthermore, it appears that individuals with impaired FMD may benefit from performing high intensity PA, whereas no relationships exist between FMD and lower intensities of PA or between PA and FMD in those subjects who possess preserved vascular function a priori. | 18,930,229 |
Synthesis and pH-dependent micellization of diblock copolymer mixtures. | This work focused on the preparation and the aqueous solution properties of hybrid polymeric micelles consisting of a hydrophobic poly(epsilon-caprolactone) (PCL) core and a mixed shell of hydrophilic poly(ethylene oxide) (PEO) and pH-sensitive poly(2-vinylpyridine) (P2VP). The hybrid micelles were successfully prepared by the rapid addition of acidic water to a binary solution of PCL(34)-b-PEO(114) and PCL(32)-b-P2VP(52) diblock copolymers in N,N-dimethylformamide. These micelles were pH-responsive as result of the pH-dependent ionization of the P2VP block. The impact of pH on the self-assembly of the binary mixture of diblocks-thus on the composition, shape, size and surface properties of the micelles-was studied by a variety of experimental techniques, i.e., dynamic and static light scattering, transmission electron microscopy, Zeta potential, fluorescence spectroscopy and complement hemolytic 50 test. | 18,930,246 |
Long acting testosterone undecanoate therapy in men with hypogonadism: results of a pharmacokinetic clinical study. | We determined the pharmacokinetics and safety of 750 mg long acting testosterone undecanoate given intramuscularly at 0, 4 and 14 weeks to men with hypogonadism. A 24-week, single arm, open label, multicenter trial in 130 hypogonadal men 18 years or older who were screened for serum total testosterone less than 300 ng/dl was performed at 31 research sites in the United States between March and November 2007. Testosterone undecanoate (750 mg) was administered at baseline, and at weeks 4 and 14. Serum testosterone samples were collected on days 4, 7, 11, 14, 21, 28, 42, 56 and 70 following injection 3. Safety was assessed, eg biochemical markers and adverse events, secondary to testosterone undecanoate treatment. Of the 130 patients 116 with a mean +/- SE age of 54.2 +/- 0.90 years completed the 24-week trial. Following the week 14 injection mean +/- SD average serum testosterone was 494.9 +/- 141.46 ng/dl during the 70-day dosing interval and mean +/- SD maximum serum testosterone was 890.6 +/- 345.11 ng/dl with a mean concentration within the young healthy adult male range (300 to 1,000 ng/dl) in 94% of patients and a mean maximum concentration of below 1,500 ng/dl in 92%. Mean +/- SE hematocrit and hemoglobin increased from baseline to week 24 (43.3% +/- 0.32% to 45.7% +/- 0.35% and 14.6 +/- 0.11 to 15.5 +/- 0.13 gm/dl, respectively). Mean +/- SE prostate specific antigen increased from baseline to 24 weeks (1.0 +/- 0.08 to 1.3 +/- 0.10 ng/ml). No prostate cancer or gynecomastia was observed during this 24-week study. This 24-week clinical study demonstrated that 750 mg testosterone undecanoate depot injection administered intramuscularly at 0, 4 and 14 weeks achieves serum testosterone levels in the normal range during a 10-week dosing interval. | 18,930,255 |
Factors predicting renal functional outcome after partial nephrectomy. | Compared to radical nephrectomy, partial nephrectomy better preserves renal parenchyma and function. Although several clinical factors may impact renal function after partial nephrectomy including preoperative function, age, gender and comorbidities, the contributions of tumor and surgical factors have not been well studied. We evaluate independent factors predicting functional outcomes after partial nephrectomy. Preoperative and all postoperative serum creatinine values for 1,169 patients undergoing partial nephrectomy were used to estimate glomerular filtration rate. Postoperative nadir glomerular filtration rate and ultimate glomerular filtration rate were analyzed using multiple pertinent covariates. Median preoperative, postoperative nadir and ultimate glomerular filtration rates were 77, 57 and 71 ml per minute per 1.73 m(2), respectively. Increasing age, gender, lower preoperative glomerular filtration rate, solitary kidney, tumor size, ischemia time and longer time to nadir glomerular filtration rate significantly predicted postoperative nadir glomerular filtration rate and ultimate glomerular filtration rate. Acute loss of renal function predicted lower ultimate glomerular filtration rate. In the entire cohort, in patients with normal preoperative renal function, and in those with baseline stage 3 and those with stage 4 chronic kidney disease the incidence of postoperative acute kidney injury after partial nephrectomy was 3.6%, 0.8%, 6.2% and 34%, and the incidence of chronic end stage renal disease after partial nephrectomy was 2.5%, 0.1%, 3.7% and 36%, respectively. Lower preoperative glomerular filtration rate, solitary kidney, older age, gender, tumor size and longer ischemic interval all predicted lower glomerular filtration rate after partial nephrectomy. Therefore, duration of renal ischemia is the strongest modifiable surgical risk factor for decreased renal function after partial nephrectomy, and efforts to limit ischemic time and injury should be pursued in open and laparoscopic partial nephrectomy. | 18,930,264 |
Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. | There is considerable interindividual diversity in the development of adverse reactions during chemotherapy for cancers. This diversity is suggested to be attributable to differences in the disposition of chemotherapeutic agents, which is modified by genetic polymorphisms. In this study we evaluated the possible association of polymorphisms of genes involved in the metabolism, detoxification and transport of the agents with adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin therapy. A total of 40 patients with urothelial cancer who received methotrexate, vinblastine, doxorubicin and cisplatin or high dose methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy between 1996 and 2005 at Akita University Medical Center were included in this study. Four genetic polymorphisms (ABCB1, GSTP1, CYP3A5 and MTHFR) and clinical parameters were included in the analysis to determine whether there was any association with the grade of adverse reactions at the first cycle and the worst grade of each adverse reaction throughout the chemotherapy period. On multivariate analysis the CYP3A5 A6986G genotype *3/*3 (OR 8.205, 95% CI 1.616-41.667, p = 0.011) and smaller number of treatment cycles (OR 0.156, 95% CI 0.037-0.659, p = 0.011) were independent factors for leukocytopenia (grade 3 or greater) throughout the period of chemotherapy. The mean white blood cell count nadir in patients with genotype *3/*3 was significantly lower than that in those with the *1 allele (1,542 +/- 903 vs 2,431 +/- 973/mm(3), p = 0.009). The A6986G polymorphism of CYP3A5, which is involved in the metabolism of vinblastine and doxorubicin, might be a genetic predictor of the severity of leukocytopenia induced by chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin. | 18,930,278 |
Degradation of phenanthrene by bacterial strain isolated from soil in oil refinery fields in Shanghai China. | A bacterial strain Pseudomonas stutzeri ZP2 was identified with phenanthrene-degrading ability based on Gram staining, oxydase reaction, biochemical tests, FAME analysis, G+C content and 16S rDNA gene sequence analysis. It is the first time that P. stutzeri is reported to process the capability for phenanthrene degradation. The strain was isolated from soil samples contaminated with polycyclic aromatic hydrocarbon (PAH)-containing waste from an oil refinery field in Shanghai, China. Strain P sp. ZP2 can utilize naphthalene, phenanthrene and Tween 80 as its sole carbon source and can degrade phenanthrene very fast, 6 days for 96% phenanthrene at 250 ppm concentration. The optimal growth conditions of strain ZP2 was determined to be at pH 8.0, 37 degrees C, respectively. The results also indicate that strain ZP2 can remove more than 90% of phenanthrene at any concentrations ranged from 250 to 1000 ppm in 6 days. It suggests that strain ZP2 can endure high concentrations of phenanthrene. Besides, the effects of non-ionic surfactants such as Brij 30, Triton X100 and Tween 80, on the phenanthrene degradation were examined. Therefore, this strain may find great application in bioremediation practices. | 18,930,349 |
Alcohol use and serious psychological distress among women of childbearing age. | The purpose of this study was to present nationally representative findings on the prevalence and co-occurrence of alcohol use and serious psychological distress among women aged 18-44 years, as well as their access to health care. A total of 24,900 women aged 18-44 years participated in the National Health Interview Survey (NHIS) during the years 2003-2005. Using data from the cross-sectional survey, we estimated the prevalence and co-occurrence of alcohol use and serious psychological distress among this population; this association was examined using logistic regression. Health care access among women who used alcohol and had serious psychological distress was characterized by co-occurring status. During the study period, the estimated annual prevalence was 4.1% for heavier alcohol use, 56.0% for non-heavier use, 39.8% for nonuse, and 3.6% for serious psychological distress among women aged 18-44 years. Women who experienced serious psychological distress were at an increased likelihood for alcohol use, particularly heavier use. Alcohol use and serious psychological distress co-occurred among an estimated 1.1 million women of childbearing age in the United States annually. Most women, regardless of their co-occurring status, reported being treated by clinicians in various health care settings during the previous 12 months. Alcohol use is common among women of childbearing age who experience serious psychological distress. The findings of this study provide support for enhancing efforts toward integrated assessment and intervention among women who have such co-occurring risk factors. | 18,930,354 |
Inhaled nitric oxide in the treatment of preterm infants. | Inhaled nitric oxide (iNO) has been used successfully in select term and near-term infants with respiratory failure. The use of iNO in the premature infant population, however, remains controversial. This article will review some of the current literature regarding the use of iNO in premature infants and discuss current recommendations and future research directions. | 18,930,359 |
Aspiration of equine oocytes from immature follicles after treatment with equine pituitary extract (EPE) alone or in combination with hCG. | This study examined the effect of treating mares with equine pituitary extract (EPE) alone or in combination with hCG on the recovery rate of immature follicles by transvaginal follicular aspiration (ovum pick-up; OPU). Ten normally cycling crossbred mares aged 3-15 years and weighing 350-400 kg were subjected to each of three treatments in a random sequence with each exposure to a new treatment separated by a rest cycle during which a spontaneous ovulation occurred. The treatments were (1) superovulated with 25mg EPE and treated with 2500 IU hCG, (2) superovulation with 25mg EPE, and (3) control (no exogenous treatment). Treatments 7 days after spontaneous ovulation; and all the follicles >10mm were aspirated 24h after the largest follicle achieved a diameter of 27-30 mm for control group, and most follicles reached 22-27 mm for the EPE alone treatment. To the group EPE+hCG, when the follicles reached 22-27 mm, hCG was administered, 24h before OPU. Superovulation increased the number of follicles available for aspiration. The total number of follicles available for aspiration was 61 in the EPE/hCG group, 63 in the EPE group and 42 in the control. The proportion of follicles aspirated varied from 63.5% to 73.8%. Oocyte recovery rate ranged from 15.0% to 16.7% and the proportion of mares that yielded at least one oocyte was 70% (7/10) in the EPE/hCG, 60% (6/10) in the EPE alone and 50% (5/10) in control group. The EPE/hCG treatment had a higher proportion of follicles with expanded granulose cells (64.4%) than the control (3.3%; p<0.05) and the EPE treatment (25.0%). The intervals from spontaneous ovulation to aspiration were similar for all treatments (11-12 days). However, superovulatory treatment significantly increased the aspiration to ovulation interval from 15+/-4 days for control to 27+/-15 days for EPE (p<0.05) and to 23+/-13 days for EPE/hCG treatment with commensurate increases in the time between spontaneous ovulations. | 18,930,362 |
Bacterial interactions and transport in unsaturated porous media. | The convection-dispersion transport model, which can well define solute transport, has been introduced to describe bacterial transport. Due to different interaction natures within the porous media, bacterial transport in the subsurface, especially in the vadose zone is a complex scenario. When transported in the vadose zone, bacteria may be captured on the media surface, at the air-water interface, or at the media-air-water three-phase interface depending upon the predominant interactions of concerned bacteria within the pore system. In this study, transport of Echerichia coli, Pseudomonas fluorescens and Bacillus subtilis in silica sand under water unsaturated conditions was investigated using column experiments. Bacterial interactions within the system were characterized based on bacterial and media surface thermodynamic properties, which were determined independently by means of contact angle measurements. These calculated interactions provided solid evidence of the bacterial retention mechanisms in the pore system, which served as the bases for suitable assumptions of bacterial transport modeling. The micro-scale interaction investigations helped eliminate uncertainties arising with bacterial transport modeling. | 18,930,382 |
Synthetic chalcones as efficient inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase PtpA. | In the search for lead compounds for new drugs for tuberculosis, the activity of 38 synthetic chalcones were assayed for their potential inhibitory action towards a protein tyrosine phosphatase from Mycobacterium tuberculosis--PtpA. The compounds were obtained by aldolic condensation between aldehydes and acetophenones, under basic conditions. Five compounds presented moderate or good activity. The structure-activity analysis reveals that the predominant factor for the activity is the molecule planarity/hydrophobicity and the nature of the substituents. | 18,930,396 |
Perylene-conjugated pyrrole polyamide as a sequence-specific fluorescent probe. | Perylene-conjugated pyrrole (Py)-polyamide 2 was designed and synthesized using the Fmoc solid-phase synthesis and a subsequent Sonogashira coupling reaction with 3-bromoperylene. Interestingly, conjugate 2 did not luminesce in water at 313 nm irradiation but was turned on in the presence of target double-stranded (ds) DNA, and showed strong emission with increasing DNA concentration, in particularly, by the binding to the target telomere sequences through heterodimer formation with partner 3. Importantly, the excitation spectrum of 2 clearly indicates that the Py and Imidazole (Im) moieties in the polyamide effectively sensitize the perylene moiety to give rise to fluorescence emission. Energy transfer would occur from the Py moiety to the perylene. Thus, screening of perylene-conjugates will allow us to develop a novel "molecular light switch" with sequence-specificity. | 18,930,403 |
Synthesis, mechanistic studies, and anti-proliferative activity of glutathione/glutathione S-transferase-activated nitric oxide prodrugs. | Nitric oxide (NO) prodrugs such as O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) are a growing class of promising NO-based therapeutics. Nitric oxide release from the anti-cancer lead compound, JS-K, is proposed to occur through a nucleophilic aromatic substitution by glutathione (GSH) catalyzed by glutathione S-transferase (GST) to form a diazeniumdiolate anion that spontaneously releases NO. In this study, a number of structural analogues of JS-K were synthesized and their chemical and biological properties were compared with those of JS-K. The homopiperazine analogue of JS-K showed anti-cancer activity that is comparable with that of JS-K but with a diminished reactivity towards both GSH and GSH/GST; both the aforementioned compounds displayed no cytotoxic activity towards normal renal epithelial cell line at concentrations where they significantly diminished the proliferation of a panel of renal cancer cell lines. These properties may prove advantageous in the further development of this class of nitric oxide prodrugs as cancer therapeutic agents. | 18,930,407 |
Shedding light on gibberellic acid signalling. | Gibberellic acid (GA) promotes a range of developmental and growth processes in plants, the most well-known being germination, elongation growth and flowering time. DELLA repressors are the key players of the pathway. Their presence or their GA-dependent turnover via the 26S proteasome correlates to a large extent with the repression or derepression, respectively, of GA-dependent growth responses. Recent progress has revealed the role of DELLA repressors in several novel response pathways, and at the biochemical level, they have now been shown to function as repressors of the PHYTOCHROME INTERACTING FACTOR3 (PIF3) and PIF4 transcriptional activators in the context of light-regulated seedling development. Furthermore, the first insights have been gained into the evolution of the GA signalling pathway on the basis of comparative genomics between the moss Physcomitrella patens, the lycophyte Selaginella moellendorffii and seed plants. | 18,930,434 |
Determination of glycemic monitoring marker 1,5-anhydroglucitol in plasma by liquid chromatography-electrospray tandem mass spectrometry. | Previous studies have shown that plasma 1,5-anhydroglucitol (1,5-AG) is markedly reduced among diabetic patients and therefore serves as a sensitive marker for short-term glycemic control. The current study describes the development of the liquid chromatography negative ion electrospray tandem mass spectrometry (LC-MS/MS) method to measure 1,5-AG in human plasma. The samples were pre-treated with protein precipitation and an isotope-labeled internal standard was used. Chromatographic separation was achieved on amide column (150 mm x 2.0mm i.d., 5 microm) followed by detection with multiple reaction monitoring mode. Linearity, accuracy, precision, recovery, matrix effect, and stability were evaluated during method validation over the range of 1-50 microg/mL. The validated method has been clinically applied among 159 type 2 diabetic patients and 290 control subjects. A marked reduction in 1,5-AG levels among the diabetic patients and significant between-gender difference in nondiabetic subjects were observed. | 18,930,443 |
Acute aerobic exercise and information processing: energizing motor processes during a choice reaction time task. | The immediate and short-term after effects of a bout of aerobic exercise on young adults' information processing were investigated. Seventeen participants performed an auditory two-choice reaction time (RT) task before, during, and after 40 min of ergometer cycling. In a separate session, the same sequence of testing was completed while seated on an ergometer without pedalling. Results indicate that exercise (1) improves the speed of reactions by energizing motor outputs; (2) interacts with the arousing effect of a loud auditory signal suggesting a direct link between arousal and activation; (3) gradually reduces RT and peaks between 15 and 20 min; (4) effects on RT disappear very quickly after exercise cessation; and (5) effects on motor processes cannot be explained by increases in body temperature caused by exercise. Taken together, these results support a selective influence of acute aerobic exercise on motor adjustment stage. | 18,930,445 |
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