title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Modulating Notch signaling by pathway-intrinsic and pathway-extrinsic mechanisms. | Despite a relatively simple core-signaling transduction machinery, Notch signaling controls cell differentiation in many different tissues and at multiple stages in a given cell lineage. To understand how Notch generates this multitude of cellular responses, it is important to learn how the Notch-signaling output is modulated at various levels. Pathway-intrinsic as well as pathway-extrinsic mechanisms, including cross-talk between Notch and other major signaling mechanisms, modulate Notch signaling, contributing to the versatile output. In this review, we discuss how Notch signaling is altered in tumors and illustrate the complexity in signaling pathway cross-talk with examples of how Notch synergizes with NF-kappaB signaling and the cellular response to lowered oxygen (hypoxia). | 18,722,525 |
Cloning and characterization of a cDNA clone encoding troponin T from tick Haemaphysalis qinghaiensis (Acari: Ixodidae). | Troponin T (TnT) is a key protein for Ca(2+)-sensitive molecular switching of muscle contraction. The entire cDNA sequence of Haemaphysalis qinghaiensis troponin T gene (HqTnT) from the hard tick was cloned here. The cDNA sequence of HqTnT possesses an ORF of 1170 bp coding for a mature protein with 389 amino acid residues and a molecular mass of 46.5 kDa. Search of the cloned sequence in GenBank revealed that HqTnT gene shared some homology with TnT genes of other organisms. By sequence comparison, two conserved domains were identified in the middle (residues 54-78) and close to the carboxyl-terminal end (residues 181-229) of the amino acid sequence of HqTnT. These conserved domains might be responsible for the interaction with tick tropomyosin and troponin I subunit, respectively. Reverse transcription-polymerase chain reaction showed a ubiquitous expression of HqTnT gene at different developmental stages and in different tissues of the tick. The HqTnT was expressed as glutathione S-transferase fused protein in a prokaryotic system. Though rHqTnT could induce specific antibodies in sheep, the antibodies could not protect sheep from the infestation of ticks. Therefore, recombinantly produced HqTnT could not be a candidate antigen for developing anti-tick vaccine. To our knowledge, this is the first report of tick TnT gene. | 18,722,546 |
Toll-like receptors in systemic lupus erythematosus; prospects for therapeutic intervention. | Recent experimental and clinical studies have placed new emphasis on the role of the innate immune system in SLE. Nucleic acid-containing immune complexes activate the innate response by engaging specific Toll-like receptors (TLRs) and promote the generation of autoantibodies. Pharmacologic modulation of TLR-directed pathways may offer new therapeutic approaches for the treatment of SLE. | 18,722,558 |
Osteochondroma developing from the xyphoid appendix into an abdominal wall scar from a previous laparotomy. | We describe herein the case of a 45-year-old man who developed an osteochondroma from the xyphoid appendix into an abdominal wall scar from a laparotomy performed 4 years previously. To our knowledge, rare cases of osteochondroma of the xyphoid bone have been documented in the literature. As shown by the tumor's rapid development during a period of only 4 years, osteochondromas arise from, or grow well under, inflammatory and cicatricial conditions. Periosteal contusion causing growth-plate cartilage migration and enchondral ossification seems to be the first presentation of osteochondroma. | 18,722,584 |
Fatigue resistance during a voluntary performance task is associated with lower levels of mobility in cerebral palsy. | To investigate muscle fatigue of the knee flexors and extensors in people with cerebral palsy (CP) compared with those without motor disability during performance of a voluntary fatigue protocol and to investigate the relationship with functional mobility. A case-control study. A biomechanics laboratory. Ambulatory subjects with CP (n=18; mean age, 17.5 y) in Gross Motor Function Classification System (GMFCS) levels I, II, and III and a comparison group of age-matched subjects (n=16) without motor disability (mean age, 16.6 y). Not applicable. The voluntary muscle fatigue protocol consisted of concentric knee flexion and extension at 60 degrees a second for 35 repetitions on an isokinetic dynamometer. Peak torque for each repetition was normalized by the maximum peak torque value. Muscle fatigue was calculated as the rate of decline in normalized peak torque across all repetitions, represented by the slope of the linear regression. Self-selected and fast gait velocities were measured as well as the Pediatric Outcomes Data Collection Instrument (PODCI). Greater fatigability (slope) was observed in the comparison group for both knee flexors and extensors than in the group with CP. Within CP, lower knee extensor fatigue (slope) was associated with lower functioning GMFCS levels and lower levels of activity and participation as measured by the PODCI transfers and basic mobility. Even after adjusting for maximum peak torque, the knee flexors and extensors of participants with CP were observed to be less fatigable than age-matched peers without motor disability. The lower rate of muscle fatigue was also associated with lower functional mobility in CP. These results may be related to strength or activation differences and/or muscle property alterations. Future investigations are warranted. | 18,722,588 |
A stochastic model of tumor angiogenesis. | Angiogenesis is a prerequisite for the growth, invasion and metastasis of solid tumors. The aim of this study was to investigate the changes of microvessel densities in tumor with a method of probability. We showed that the stages of tumor angiogenesis may follow a probabilistic pattern compatible with Markov chain and this could be of prognostic importance. The system was simulated with 10,000 patients in order to show the applicability of this method. This approach may improve classification schemes and perhaps make diagnosis and treatment more individualized to patients. | 18,722,598 |
Prevalence and risk factors of irritable bowel syndrome in Korean adolescent girls: a school-based study. | Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, with a strong female predominance. When compared to the vast knowledge pertaining to adults with IBS, very little is known about IBS in the adolescent population. In Korea, the field of adolescent health with IBS is just beginning to develop, so there is still a lack of information concerning the prevalence of IBS in adolescent groups. The purposes of this study were to explore the prevalence of IBS among Korean adolescent girls, and identify the risk factors affecting IBS occurrence. This study adopted a cross-sectional descriptive design using the self-reported questionnaire. A total of 405 adolescent females were recruited from 5 academic high schools in Korea in August and September of 2007. IBS was diagnosed based on the Rome II criteria. For the evaluation of risk factors on the IBS, we investigated dietary habit, life style, stress, anxiety, depression, and premenstrual syndrome (PMS). The prevalence of IBS according to Rome II criteria was 25.7% in the subjects. The multivariate logistic regression analyses revealed that higher stress (OR 2.25, 95% CI 1.13-4.48), anxiety (OR 4.27, 95% CI 1.09-16.71), and depression (OR 10.87, 95% CI 1.14-103.81) were independently associated with increased IBS occurrence. The prevalence of IBS in female adolescent students from this study was higher compared with those reported in the Western countries. This study provides much need information about the relatively unstudied Korean female adolescents in terms of IBS issues and aspects of psychological attributes to IBS. This study has the potential to influence the development of better promotion programs for adolescents and women's health. | 18,722,617 |
High dietary menaquinone intake is associated with reduced coronary calcification. | Dietary vitamin K is thought to decrease risk of cardiovascular disease by reducing coronary calcification, but inconsistent results are reported. This may be due to different effects of vitamin K(1) (phylloquinone) and vitamin K(2) (menaquinone, MK), but few studies included both. We investigated the association of intake of phylloquinone and menaquinone, including its subtypes (MK4-MK10), with coronary calcification in a cross-sectional study among 564 post-menopausal women. Phylloquinone and menaquinone intake was estimated using a food-frequency questionnaire. Sixty-two percent (n=360) of the women had coronary calcification based on 1.5-mm thick slices. Phylloquinone intake was not associated with coronary calcification with a relative risk (RR) of 1.17 (95%-confidence interval: 0.96-1.42; p(trend)=0.11) of the highest versus lowest quartile. Menaquinone intake was associated with decreased coronary calcification with an RR of 0.80 (95%-CI: 0.65-0.98; p(trend)=0.03). This study shows that high dietary menaquinone intake, but probably not phylloquinone, is associated with reduced coronary calcification. Adequate menaquinone intakes could therefore be important to prevent cardiovascular disease. | 18,722,618 |
Adult Wilms tumor during gestational period. | We present a case of a 17-year-old pregnant girl, with hematuria. Magnetic resonance imaging showed a solid left renal mass. The patient had a radical nephrectomy during the 20th week gestation and the diagnosis was nephroblastoma. She gave birth to a healthy child at term and refused adjuvant treatment. She is disease-free after 24 months of follow-up. Based on the excellent results achieved while treating children with Wilms' tumor using surgery, chemotherapy and radiotherapy, adults with the same disease should be treated similarly. This treatment must be instituted early, even in pregnant women. | 18,722,653 |
Subacute toxicity of polychlorinated naphthalenes and their effect on cytochrome P-450. | The aim of the study was to investigate the subacute toxicity of a polychlorinated naphthalene (PCN) mixture and its effect on cytochrome P-450 levels in rats. The animals were administered PCNs intragastrically in repeated daily doses of 1, 10, and 100 mg/kg. The animals were dissected after 7, 14, or 21 doses. Doses of 10 and 100 mg/kg induced a significant decrease in the body weight at all time points of the experiment compared with the control group. The exposure to PCNs increased both the level of total cytochrome P-450 and the activity of CYP 1A at the same time points. In the groups of rats given PCNs in doses of 10 and 100 mg/kg, an evident dose- and time-dependent increase in malondialdehyde (MDA) level was observed throughout the experiment. The correlation between the increased MDA and decreased glutathione (GSH) levels in the liver was also observed. | 18,722,660 |
Chitosan microspheres as candidate plasmid vaccine carrier for oral immunisation of Japanese flounder (Paralichthys olivaceus). | Oral DNA-based immunotherapy is a new treatment option for fish immunisation in intensive culture. However, because of the existence of the nucleases and severe gastrointestinal conditions, DNA-based vaccines can be hydrolyzed or denatured. In our laboratory, a plasmid DNA (pDNA) containing major capsid protein (MCP) gene of lymphocystis disease virus (LCDV) was prepared, and then pDNA was encapsulated in chitosan microspheres through an emulsion-based methodology. The yield, loading percent and encapsulation efficiency of microspheres were 93.6%, 0.3% and 94.5%, respectively. Scanning electron microscopy (SEM) showed that pDNA-loaded microspheres yielded a spherical shape with smooth surfaces. The disproportion of super-coiled to open circle and linear pDNA suggested that high transfection efficiencies of pDNA in microspheres were retained. The cumulative release of pDNA showed that chitosan microspheres were resistant to degradation in simulated gastrointestinal tract environment. The release profile at PBS buffer (pH 7.4) displayed that pDNA-loaded chitosan microspheres had a release up to 42 days after intestinal imbibition. RT-PCR showed that RNA containing information of MCP gene existed in various tissues 10-90 days post-vaccination. SDS-PAGE and immunofluorescent images indicated that pDNA expressed MCP in tissues of fish 10-90 days after oral administration. In addition, indirect ELISA displayed that the immune responses of sera were positive (O.D.> or =0.3) from week 1 to week 16 for fish vaccinated with microspheres, in comparison with fish vaccinated with naked pDNA. Data obtained suggested that chitosan microspheres were promising carriers for oral pDNA vaccine. Because this encapsulation technique was easy to operate and immunisation efficacy of microspheres loaded with pDNA was significant, it had potential to be used in drug delivery applications. | 18,722,672 |
Dose-individualized stereotactic body radiotherapy for T1-3N0 non-small cell lung cancer: long-term results and efficacy of adjuvant chemotherapy. | To evaluate the efficacy of dose-individualized stereotactic body radiotherapy (SBRT) and adjuvant chemotherapy in stage T1-3N0M0 non-small cell lung cancer (NSCLC). Sixty-five patients with T1-3N0M0 NSCLC treated by SBRT between April 2001 and August 2005 were included. Twenty patients were CT-staged at stage T1, 34 at stage T2, and 11 at stage T3. All patients underwent no elective nodal irradiation. SBRT total doses ranged from 71.8 to 115.2Gy of biological equivalent dose (BED) in 3.6 to 8.0Gy daily fractions. Seventeen patients were offered cisplatin-containing adjuvant chemotherapy. The overall response rate was 90.6% at six months. The 3- and 5-year overall survival rates for all patients were 57.3% and 35.1%, respectively, and for stage T1-2 patients these were 60.2, 36.5%, respectively. Of all patients, the 3- and 5-year overall survival rates of adjuvant chemotherapy group were 80.5% and 46.0%, respectively, and those of patients with SBRT alone were 49.6% and 31.5%, respectively. Patients who accepted adjuvant chemotherapy had a lower relapse rate and better overall survival. Acute toxicities were mild, and no long-term toxicity was observed. Patients treated with the dose-individualization strategy of SBRT showed excellent local control and improved survival. Adjuvant chemotherapy may reduce the frequency of relapse and increase overall survival in stage at T1-3N0M0 NSCLC patients. | 18,722,684 |
Effect of cationic and anionic surfactants on the sorption and desorption of perfluorooctane sulfonate (PFOS) on natural sediments. | Sorption and desorption of PFOS at water-sediment interfaces were investigated in the presence of a cationic surfactant, cetyltrimethylammonium bromide (CTAB), and an anionic surfactant, sodium dodecylbenzene sulfonate (SDBS). CTAB remarkably enhanced the sorption of PFOS on the sediment. In contrast, the influence of SDBS to the sorption of PFOS was concentration dependent. Two contrasting factors were responsible for the phenomenon. One was the sorption of the surfactant itself to the sediment, which enhanced the sorption of PFOS. The other was the increase in solubility of PFOS caused by the adding of surfactants, which decreased the sorption of PFOS. SDBS had a much lower sorption capacity, but rather strong ability to increase the solubility of PFOS. High levels of SDBS remarkably reduced the sorption of PFOS on the sediment. These results imply that cationic and anionic surfactants may have contrast impacts on the distribution and transport of PFOS in the environment. | 18,722,698 |
Sensor-based neuronavigation: evaluation of a large continuous patient population. | Navigation systems enable neurosurgeons to guide operations with imaging data. Sensor-based neuronavigation uses an electromagnetic field and sensors to measure the positions of the patient's brain anatomy and the surgical instruments. The aim of this investigation was to determine the accuracy level of sensor-based tracking in a large patient collection. This study covers 250 patients operated upon during a continuous 5.5-year period. The patients had a wide range of indications and surgical procedures. The operations were performed with a direct current (DC) pulsed sensor-based electromagnetic navigation system. Four kinds of errors were measured: the fiducial registration error (FRE), the target registration error (TRE), brain shift, and the position error (PE). These errors were calculated for five subgroups of indications: target determination and trajectory guidance, functional navigation, skull base and neurocranium, determination of resection volume, and transnasal and transsphenoidal access. The overall mean FRE was 1.66mm (+/-0.61mm). The overall mean TREs were 1.33mm (+/-0.51mm) centroid and 1.59mm (+/-0.57mm) lesional. The overall mean brain shift for applicable cases was 1.61mm (+/-1.14mm). The overall mean PE was 0.92mm (+/-0.54mm). By and large, modern sensor-based neuronavigation operates within an acceptable and commonplace degree of error. However, the neurosurgeon must remain critical in cases of small lesions, and must exert caution not to introduce further interference from metal objects or electromagnetic devices. | 18,722,707 |
Olive mill wastewater degradation by Fenton oxidation with zero-valent iron and hydrogen peroxide. | The degradation of olive mill wastewater (OMW) with hydroxyl radicals generated from zero-valent iron and hydrogen peroxide has been investigated by means of chemical oxygen demand (COD) and phenolic compounds analyses. The effects of the H2O2 dose, the pH and the organic matter concentration have been studied. The optimal experimental conditions were found to have continuous presence of iron metal, acid pH (2.0-4.0), and relatively concentrated hydrogen peroxide (9.5M). Coloration of OMW disappeared and phenolic compound decreased to 50% of initial concentration after 3h reaction time. The application of zero-valent Fe/H2O2 procedure permitted high removal efficiencies of pollutants from olive mill wastewater. The results show that zero-valent Fe/H2O2 could be considered as an effective alternative solution for the treatment of OMW or may be combined with a classical biological process to achieve high quality of effluent water. | 18,722,712 |
[Current data on vaccines for respiratory diseases]. | Respiratory tract infections are a major reason of antibiotic prescription. Some of these infections can be prevented by vaccination. In France, the main new data concerns the following vaccines: Haemophilus influenzae: besides the vaccine effectiveness H. influenzae b, that is a virulent capsulated strain, a polyvalent vaccine effective against non-capsulated strains, responsible for otitis media, is under development. Pneumococci: the conjugated heptavalent vaccine recommended for all infants in the USA since the year 2000 allowed a dramatic drop in the incidence of invasive infections and of otitis media due to pneumococci, with an indirect impact reducing the frequency of pneumonia in adults. Influenza: the vaccinal coverage remains insufficient in people targeted by recommendations, particularly in health care workers. New recommendations concern some travel agents, people living in close contact with infants at risk and women immediately after delivery of a newborn at risk. Pertussis: the vaccinal coverage of preadolescents is insufficient. Vaccination of adults is mainly recommended for people who are expected to be in close contact with newborns (health care workers, parents). Tuberculosis: BCG vaccination is no longer mandatory, but is now strongly recommended for all infants in the greater Paris area, French Guyana, and for all infants at risk, especially immigrants depending on their native country. Varicella: universal vaccination is not recommended. To prevent respiratory complications in adults, the vaccine is now recommended for all varicella naive teenagers. | 18,722,726 |
Clinical analysis of hyponatremia in acute craniocerebral injury. | To explore pathological mechanisms of central hyponatremia and its treatment. Synchronous assay was made for changes of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), endogenous digitalis-like substance (EDLS), antidiuretic hormone (ADH) in blood, and Na(+) concentrations in blood and urine, and plasma- and urine-osmolality in 68 patients with acute craniocerebral injury (ACI). Of the 68 patients with ACI, 27 were found to have hyponatremia, and such illness was mostly concentrated on severe cases. The central hyponatremia in patients with ACI may be related to the increase in the secretion of EDLS and ADH as the result of damaged functions of the hypothalamic-hypophysial system, and it seems that the decrease in blood ANP and BNP has no direct effect on Na(+) concentrations in blood. Inappropriate secretion of antidiuretic hormone syndrome and cerebral salt-wasting syndrome are the two main reasons for hyponatremia in patients with craniocerebral injury. The pathological mechanism, diagnostic standards, as well as treatment methods for the two, however, are not just the same. Intravenous injection of extrinsic thyrotropin-releasing hormone might inhibit dilutional hyponatremia arising from the increase in ADH secretion by patients with ACI. | 18,722,740 |
Selective axillary node sampling and radiotherapy to the axilla in the management of breast cancer. | Axillary treatment for patients with early-stage breast cancer can be associated with considerable morbidity. Techniques, such as axillary node sampling (ANS) and, more recently, sentinel node biopsy, in combination with radiotherapy have the potential to reduce toxicity. A retrospective review of axillary treatment in patients with early-stage breast cancer treated at our institution between 1997 and 2003 was carried out to assess the outcome and morbidity of ANS in combination with radiotherapy. The treatment policy was to carry out four-node, Edinburgh-style ANS except in those cases with either palpably enlarged nodes or cytological confirmation of involvement or with clinically obvious node involvement at surgery when level 2 axillary node clearance (ANC) was carried out. Patients with involved nodes after ANS received postoperative axillary radiotherapy. In total, 381 patients were included, 331 received ANS and 50 received ANC. The median follow-up was 6.5 years and overall survival at 5 years was 84%. Pathologically involved nodes were found in 152/331 (50%) ANS patients and 43/50 (86%) ANC patients. The rate of local recurrence (breast or chest wall) at 5 years was 4% (95% confidence interval 1-17%) in the ANC group and 2% (95% confidence interval 1-4%) in the ANS group. The nodal recurrence rate of those undergoing ANS was 3% (11/331) compared with 6% (3/50) for those treated by ANC. The rate of clinically significant lymphoedema at 5 years was significantly higher (P=0.01) in the ANC arm: 18% (95% confidence interval 9-32%) compared with 5% (95% confidence interval 3-8%) in those treated by ANS. Thirty-one cases received additional supraclavicular fossa irradiation because of the involvement of more than four nodes on ANS, which may not have been available with sentinel node biopsy and has implications for current practice. Selective ANS with the removal of a minimum of four nodes guides optimal locoregional treatment with good local control rates, low overall morbidity and may obviate the need for a second surgical procedure. | 18,722,758 |
On-chip detection of protein glycosylation based on energy transfer between nanoparticles. | We describe a chip-based method to detect protein glycosylation based on the energy transfer between quantum dots (QDs) and gold nanoparticles (AuNPs). Our assay system relies on modulations in the energy transfer between the nanoparticles on a surface. The photoluminescence (PL) of lectin-coated QDs (energy donor) immobilized on a glass slide is quenched by carbohydrate-coated AuNPs (energy acceptor), and the presence of the glycoprotein causes the increase of the PL of QDs. As a proof-of-concept, Concanavalin A-coated QDs (ConA-QDs) and dextran-coated AuNPs (Dex-AuNPs) were used to detect the mannosylated proteins. As a result, the PL intensity of QDs was found to be linearly correlated with the concentration and the number of glycan moiety of the glycoprotein. We anticipated that our simple assay system will find applications for the analysis of glycoproteins with high selectivity and sensitivity in a high-throughput manner. | 18,722,763 |
The efficacy of adjuvant chemotherapy with 5-fluorouracil in colorectal cancer depends on the mismatch repair status. | The aim of this study is to evaluate if mismatch repair (MMR) defective colorectal cancer has a different response to adjuvant 5-fluorouracil (5-FU) chemotherapy in a cohort of patients prospectively followed during 5 years. The cohort included 754 surgically treated patients with colorectal cancer. MMR status was diagnosed by MLH1 and MSH2 immunohistochemistry and microsatellite instability analysis. Median follow-up was 49.2 months (range 1-73). At inclusion, 505 patients were diagnosed as TNM II or III stage, analysis of the efficacy of adjuvant chemotherapy was made on this population. Adjuvant chemotherapy was applied to 248 patients (98.2% 5-FU based). MMR deficiency was found in 76 patients (10.1%). No differences were found in overall survival (log-rank p=0.3) or disease-free survival (log-rank p=0.3) regarding MMR status. Adjuvant chemotherapy improves survival in patients in the II or III stage, but this improvement is only evident in patients with MMR-competent tumours (log-rank p=0.00001). Survival of patients with MMR-defective tumours does not improve with adjuvant chemotherapy (log-rank p=0.7). A multivariate analysis showed an independent effect of the interaction between MMR status and adjuvant chemotherapy (Hazard ratio 2.04; 95% confidence interval: 1.42-2.93). In a cohort of colorectal cancer patients, those with MMR-deficient tumours seem not to benefit from 5-FU-based chemotherapy. | 18,722,765 |
ortho-dihydroxyisoflavone derivatives from aged Doenjang (Korean fermented soypaste) and its radical scavenging activity. | One new ortho-dihydroxyisoflavone, 7,3',4'-trihydroxyisoflavone (2), and two known ortho-dihydroxyisoflavone derivatives were isolated from 5-year-old Doenjang (Korean fermented soypaste), and evaluated as potent antioxidant by comparing with other known isoflavones. 7,8,4'-Trihydroxyisoflavone (1), 7,3',4'-trihydroxyisoflavone (2), and 6,7,4'-trihydroxyisoflavone (3) inhibited DPPH (Diphenyl-1-picryl hydrazyl) formation by 50% at a concentration of 21.5+/-0.2, 28.7+/-0.4 and 32.6+/-0.6 (IC(50)), respectively, whereas three isoflavones showed weak DPPH radical scavenging activity. In xanthine oxidase (XO) system, in which both inhibition of xanthine oxidase and superoxide scavenging effect were measured in one assay. Compound 1 (IC(50)= 6.6+/-0.4 microM) and 2 (IC(50)=16.8+/-1.2 microM) show significant inhibitory activity and greater effect than allopurinol. But, compound 3 and other isoflavones showed lower inhibition activity. This study shows that the position of hydroxyl substituent at the aromatic ring of isoflavone plays an important role in radical scavenging effect. | 18,722,771 |
Optimizing patellofemoral arthroplasty. | Patellofemoral arthroplasty (PFA) has been an option for patients with symptomatic patellofemoral osteoarthritis since the 1950's. Many of the early failures resulted from a combination of implant design and surgeon technique. The goal of this overview is not to review the history of PFA, but rather to explore options for surgeons to optimize long-term outcomes and improve patient knee function, while highlighting the differing techniques required in PFA with those routinely adopted in total knee arthroplasty (TKA). | 18,722,775 |
Fat diet and alcohol-induced steatohepatitis after LPS challenge in mice: role of bioactive TNF and Th1 type cytokines. | Obesity with insulin resistance and alcohol are the most frequent causes of steatohepatitis. This work investigates the contribution of bioactive TNF and Th1 type cytokines in a mouse model of steatohepatitis induced by FAT alone or FAT+EtOH and endotoxin. The extent of liver injury and cytokine activation induced by endotoxin in chronic FAT-fed mice, FAT+EtOH-fed mice, or mice fed standard chow were analyzed. Endotoxin administration to either FAT-fed or FAT+EtOH-fed mice increased serum ALT and AST compared to standard chow mice. Immunoreactive TNF was strongly activated by LPS in FAT-fed and FAT+EtOH-fed mice which presented the highest levels, but low levels were found in standard chow mice. In contrast, bioactive TNF was only present in serum of FAT-fed and in particular the highest levels were found in FAT+EtOH-fed mice. Moreover, soluble TNFR2 but not TNFR1 was found in lower amounts in serum of FAT+EtOH-fed mice compared to FAT-fed mice. Steatohepatitis was associated with increased IL-6, IFN-gamma, and iNOS mRNA and proteins. Data show that a moderately FAT diet and low-dose EtOH concur to generate steatohepatitis and TNF liver expression after LPS. In this model, changes in the regulation of TNF are associated with increased expression of IL-6, IFN-gamma, and iNOS. | 18,722,787 |
Care in people 60 years of age and over with chronic or recently diagnosed epilepsy: a note review in United Kingdom general practice. | To ascertain present United Kingdom (UK) management processes for epilepsy in older people. This was a general practice notes review of people being treated for epilepsy 60 years and over. The cohort of 110 was from six practices. Seizure frequency in older people with epilepsy appears lower than in general; 75% are seizure free. This compares with 40-60% of people in other general practice note reviews and audits, where age is not a factor. Out of the people still having seizures over half have less than one seizure per month. Monotherapy rates are similar to the population in general. Nobody was taking more than two AEDs. There is evidence of new AED use, especially lamotrigine; it is the most commonly prescribed AED in those diagnosed in later life. Geriatricians appear to receive virtually no referrals for the diagnosis of epilepsy. General physicians, psychiatrists and neurologists receive many more. Geriatricians and general physicians appear never to follow up older people with epilepsy; GPs following up 91%, and neurologists and specialist nurses 9%. Seizure frequency in older people with epilepsy is generally low. Geriatricians appear to receive virtually no referrals for the diagnosis or management of epilepsy in older people. Follow up is mainly undertaken by GPs. Although lamotrigine has a difficult dosing schedule, which may be confusing for some older people, its use is high perhaps reflecting recent guidelines and evidence. These results may be peculiar to the geographical area used, so other work is needed to confirm or refute these findings. | 18,722,793 |
Endovascular therapy of a symptomatic mobile thrombus of the thoracic aorta. | The therapeutic strategies of a mobile luminal thrombus of the descending thoracic aorta with peripheral arterial embolization remain a matter of debate. We report the case of recurrent peripheral arterial embolism caused by a mobile thrombus of the descending aorta, which was successfully treated by implanting an endovascular stent graft. Our case demonstrates, that endovascular stent graft placement is feasible and can be performed as an effective and minimally invasive treatment option for mobile thoracic aortic thrombi. | 18,722,794 |
DFT based computational study on the excited state intramolecular proton transfer processes in o-hydroxybenzaldehyde. | Potential energy (PE) curves for the intramolecular proton transfer in the ground (GSIPT) and excited (ESIPT) states of o-hydroxybenzaldehyde (OHBA) were studied using DFT-B3LYP/6-31G(d) and TD-DFT-B3LYP/6-31G(d) level of theory, respectively. Our calculations suggest the non-viability of ground state intramolecular proton transfer in this compound. Excited states PE calculations support the ESIPT process in OHBA. The contour PE diagram and the variation of oscillator strength along the proton transfer co-ordinate support the dual emission in OHBA. Our calculations also support the experimental observations of Nagaoka et al. [S. Nagaoka, U. Nagashima, N. Ohta, M. Fujita, T. Takemura, J. Phys. Chem. 92 (1988) 166], i.e. normal emission of the title compound comes from S(2) state and the red-shifted proton transfer band appears from the S(1) state. ESIPT process has also been explained in terms of HOMO and LUMO electron density of the enol and keto tautomer of OHBA and from the potential energy surfaces. | 18,722,808 |
Parasympathetic response to acute stress is attenuated in young Zucker obese rats. | We compared arterial blood pressure (BP) and heart rate (HR) control in 9- to 11-week old obese Zucker rats (n=10; weight=452+/-45 g, average+/-SD) to age-matched, lean Zucker animals (n=13; weight=280+/-46 g). BP was measured by indwelling catheter. Baseline pressure was 113.1+/-7.0 mm Hg in the lean vs. 111.7+/-5.6 in the obese rats (NS). Baseline HR was 413+/-43 in the lean vs. 422+/-22 bpm in the obese animals (NS). Rats were classically conditioned by following a 15-second tone (CS+) with a 0.5-second tail shock. There were no between-group differences in the BP response to CS+. Conversely, heart rate (HR) decreased significantly (p<0.05) more during the last 10 s of the tone in the lean group (-46.0+/-21.5 bpm) vs. the obese (-17.8+/-21.7 bpm). This bradycardia was blocked by atropine. Finally, the change in HR divided by the change in arterial BP (DeltaHR/DeltaBP) following an intravenous bolus of phenylephrine (PE; 5 microg/kg) and following sodium nitroprusside (NP; 5 microg/kg) was determined. The DeltaHR/DeltaBP following PE was smaller in the obese (n=6; -1.36+/-0.60) vs. lean (n=5; -2.80+/-0.92); there was no difference in the response following NP. These data indicate that the BP response to a behavioral challenge did not differ in the obese rat vs. the lean animal, but that the obese subjects had an attenuated parasympathetic response to the stress, probably secondary to alterations in baroreflex function. | 18,722,824 |
Pulmonary function in the morbidly obese. | Only limited data exist on the relationship of lung function to patients with extreme obesity. To assess the relationship between lung function tests and clinical characteristics in a cohort of morbidly obese patients undergoing evaluation for bariatric procedures in a university hospital in the United States. Consecutive patients undergoing clinical evaluation were reviewed. The variables included demographic, anthropometric, clinical, and pulmonary function data. A total of 229 patients underwent a standardized preoperative evaluation. Of these 229 patients, 136 (59%) had evaluable data and 102 (75%) were women. The mean +/- standard deviation age was 45 +/- 10 years, the mean weight was 164 +/- 42 kg, and the mean body mass index was 57 +/- 13 kg/m2. Smoking or asthma was reported in 38% and 24% of patients, respectively. The mean forced vital capacity and forced expiratory volume in 1 s was 80% +/- 17% of predicted and 76% +/- 19% of predicted, respectively. Of the 136 patients, 29% had a measured forced expiratory volume in 1 s/forced vital capacity of >or=.08 below the predicted ratio. The mean total lung capacity was 86% +/- 14% of predicted; 26% of subjects had a total lung capacity <80% of predicted. Multivariate logistic regression analysis demonstrated an association of obstructive ventilatory defects with male gender (odds ratio [OR] 2.35, 95% confidence interval [CI] 1.00-5.50) and current or previous smoking (OR 2.41, 95% CI 1.10-5.30), but not body mass index. Restrictive defects were associated with body mass index (OR 1.06, 95% CI 1.01-1.10), in particular, obesity hypoventilation syndrome (OR 3.7, 95% CI 1.2-11.1). The mean preoperative spirometry, lung volumes, and gas exchange values were within the established reference ranges. Restrictive ventilatory defects were less common than obstructive ventilatory patterns and were most prominently associated with obesity hypoventilation syndrome. | 18,722,823 |
Closure of a contained open abdomen using a bipedicled myofascial oblique rectus abdominis flap technique. | A contained open abdomen is commonly used during damage control laparotomy and consists of the temporary coverage of the abdomen for protection of the viscera and reduction of intra-abdominal pressure. Definitive closure of a contained open abdomen is technically difficult due to the inability to obtain primary fascial suture. The insertion of a prosthetic mesh can be complicated with enterocutaneous fistula, and other definitive closure techniques need several surgical procedures. We describe a low cost technique that allows definitive closure of large abdominal wall defects avoiding the risk of intestinal fistula. | 18,722,829 |
Evaluating the evidence: guidelines. | Guidelines are collections of practical information that assist with clinical decision making. Evidence-based guideline development includes a critique of the quality and an evaluation of the strength of published evidence. Evolution From opinion-based to evidence-based guidelines is incomplete in many of the organizations that author them, so perioperative nurses must become skillful at critiquing guideline development methodologies and clinical content. The AGREE instrument is useful for evaluating guideline development. Nurses have access to evidence-based guidelines registered online through the National Guideline Clearinghouse. | 18,722,835 |
Controlled-substance returns in the operating suite. | Drug diversion is an ongoing problem in health care settings. The potential for drug diversion incidents in the perioperative area is high because of the availability of narcotics and other controlled substances and the stresses of working in this environment. The flow of controlled substances traditionally has been monitored by various accounting systems, but these systems can be inaccurate because the returned medications rarely are tested to verify that they have not been diluted or replaced. Returned medications are not routinely tested because of the expense and time involved. Enhanced photoemission spectroscopy is one technology that can validate returned medications quickly and inexpensively. | 18,722,838 |
Role of spiral computed tomography with 3-dimensional reconstruction in cases with laryngeal stenosis--a radioclinical correlation. | To study the efficacy of spiral computed tomography with 3-dimensional reconstruction (SCT-3DI) and endoscopy in cases with laryngeal stenosis with regard to site, type, grade, and length of stenosis and to determine the correlation among the findings of SCT-3DI, endoscopy, and surgery. This prospective study on 30 cases of laryngotracheal stenosis (acquired = 28 cases, congenital = 2 cases) was conducted in the Department of Otorhinolaryngology and Head Neck Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India, from 2001 to 2003. All patients were evaluated by SCT-3DI and rigid endoscopy. Twenty-three patients underwent open surgical procedure, and 7 patients underwent endoscopic dilatation. Correlation was established among the findings of SCT-3DI, endoscopy, and surgery by Pearson correlation coefficient (r), paired t test, and chi(2) test. Findings of SCT-3DI, endoscopy, and surgery were found to well correlate with each other. SCT-3DI was found to be less accurate in measuring the exact length of stenosis but could measure the length of stenosis in all cases, whereas by endoscopy, the measurements could be made accurately in 14 cases (46.6%). The endoscopy was more accurate in diagnosing the site and grade of stenosis (P < .01). SCT-3DI gave 18.6% false-positive result regarding involvement of glottis in stenosis. A significant difference was found between endoscopy and SCT-3DI for grade III and IV stenoses (P < .01), and SCT-3DI found to give false-positive result in 19.2% cases for grade IV stenosis. SCT-3DI was found to be a better diagnosing modality in differentiating the circumferential Gupta and Parida. SCT-3DI was found to give a false-positive result in 19.2% cases for grade IV stenosis. SCT-3DI was found to be better a diagnosing modality in differentiating the circumferential and eccentric stenosis (P < .01) and to detect the cricoid and thyroid cartilage fracture, double stenosis, and laryngocele. A false-positive rate of 33.3% was seen in diagnosing fracture of cricoid cartilage on radiology. The findings of SCT-3DI, endoscopy, and surgery well correlated with each other. Findings of SCT-3DI and rigid endoscopy are complementary to each other for a better surgical planning and outcome. | 18,722,886 |
Internal pedal amputations. | Internal pedal amputation consists of resection of the metatarsals, midtarsal bones, or talus with preservation of the toes and soft-tissue envelope. Although used in the past for the treatment of tuberculosis within the pedal skeleton, internal pedal amputations have become almost forgotten, historical procedures. However, following internal pedal amputations of a diabetic patient, the foot undergoes significant contracture that results in a stable, functional, foreshortened residual foot capable of being protected in custom-molded shoe gear with external or in-shoe orthoses. The author presents the surgical approach and postoperative treatment regime for each form of internal pedal amputation, as well as "pearls" for success. | 18,722,904 |
Minimally invasive soft-tissue and osseous stabilization (MISOS) technique for midfoot and hindfoot deformities. | The surgical repair of unstable midfoot and hindfoot deformities in the high-risk patient remains a challenge with little guidance available in the literature. The author presents a proposed surgical intervention for midfoot and hindfoot deformities utilizing a minimally invasive soft-tissue and osseous stabilization (MISOS) approach. The article presents a detailed, step-by-step description of the procedure used for these difficult limb salvage cases. | 18,722,905 |
Percutaneous bone marrow aspirate and bone graft harvesting techniques in the lower extremity. | Autogenous bone marrow aspirate and cancellous bone graft represent a useful adjuvant to enhance soft tissue and osseous healing in high-risk patients. The authors present a review of the pertinent literature and step-by-step guidelines for performing reliable, simple, and reproducible percutaneous surgical techniques to harvest autogenous bone marrow aspirate and cancellous bone graft from the proximal medial tibial metaphysis and lateral calcaneus. In addition, these techniques are associated with low morbidity and financial cost. | 18,722,909 |
Regional chemotherapy: overview. | Regional chemotherapy was developed in the 1950s and continues to play an integral part in the development of newer therapies for advanced solid malignancies. Regional therapies have evolved in complexity but are still based on the pharmacokinetics of drug delivery to solid malignancies. Newer techniques demonstrate that the combination of regional therapies, hyperthermia, and surgery is essential in promoting improved patient outcomes. | 18,722,914 |
Regional chemotherapy for carcinoma of the lung. | The potential benefit of regional chemotherapy is to reach high local drug concentrations in the treated area by reducing systemic side effects. Today, different application forms are available, such as intra-arterial infusion, sometimes in form of chemoembolization; intracavitary application techniques, such as intrapleural infusion or intraperitoneal perfusion; and isolated perfusion techniques, such as extremity perfusion or pelvic stop-flow perfusions. Up to now, only a few of these techniques have reached a level of standardization combined with an efficacy superior to conventional systemic chemotherapy to be accepted as a standard treatment by the oncologic community. This article will deal with the problems of regional chemotherapy for the treatment of carcinoma of the lung. | 18,722,925 |
Longterm results of a prospective study of 225 femoral hernia repairs: indications for tissue and mesh repair. | Femoral hernias are uncommon, and there are relatively few clinical studies of longterm outcomes after repair. Although the McVay repair has been classically described, the infrainguinal plug technique has gained popularity in recent years. Evidence supporting these repairs is sparse. A prospective study of elective femoral hernia repairs was done at the Shouldice Hospital from June 1999 until June 2003. The tissue-based complete groin repair (CGR) and a preperitoneal mesh repair were performed for specific indications. Patients were followed annually for 5 years to examine for recurrences and complications. Two hundred fifty-six patients were enrolled, with 225 completing 5 years of followup. Median age was 55 years, and hernias on the right side were more common (63.1%). Concurrent inguinal hernias were found in 115 patients (51%), and 41 (18.2%) had a previous inguinal hernia repair. A complete groin repair was performed in 120 patients and a preperitoneal mesh repair in 78. The remaining had an infrainguinal mesh repair. The overall recurrence rate was 3.1%, with a median time to recurrence of 12 months. There was no significant difference between mesh and suture repairs. Chronic postoperative pain was experienced by 20 patients (8.9%). Femoral hernias can be repaired electively with a tissue-based or a preperitoneal mesh technique, with durable longterm results. Mesh repair is indicated for recurrent femoral hernias, inguinofemoral hernias, prevascular hernias, association with concurrent direct hernias, and, if tension is anticipated, with complete groin repair. Infrainguinal mesh repair is used only when there has been a successful previous inguinal hernia repair. | 18,722,941 |
Treatment of uterine myomas with transvaginal uterine artery occlusion: possibilities and limitations. | The objective of this pilot study was to evaluate the feasibility of a transvaginal clamp prototype used for temporary uterine artery occlusion as a treatment for myomas. In particular, we aimed to evaluate technical aspects of successful occlusion with angiography and magnetic resonance imaging (MRI) and to evaluate possible ureter occlusion with pyelography. Ten premenopausal women aged 34 to 37 years with menorrhagia and myomas were treated with a temporary uterine artery occlusion for 6 hours. Five patients did not complete the clamping procedure because of unsuccessful clamping. While the clamp was in position, angiographic examination of the uterine arteries and pyelography were performed in 8 of the patients. The clamps occluded both uterine arteries in 4 patients and 1 side in another 2. Two procedures occluded the ureter unilaterally. MRI with contrast was done before, the day after, and 3 months after the procedure. Three of 5 patients who completed the clamp treatment had reduced or no contrast enhancement at MRI afterward. Clinical effects were obtained in 3 patients. Difficulties with application of the vaginal clamp were related to initial learning and size of the myomas. Our initial experience shows that the treatment is feasible in some patients with symptomatic myomas. However, improvement of the technique and equipment is needed. Care with regard to the ureters is required during further studies aimed at evaluating this approach. | 18,722,975 |
Clinico-pathological effects of Schistosoma mansoni infection associated with simultaneous exposure to malathion in Swiss outbred albino mice. | To investigate whether infection of Swiss outbred mice with the digenetic fluke Schistosoma mansoni is influenced by exposure to environmental pollutants, experimentally infected mice were exposed to 200 and 400 mg/kg of malathion. Pathology of liver and spleen, worm burden and levels of key hematological, biochemical and liver enzymes parameters of these mice were evaluated and were compared with data from infected, unexposed mice, uninfected, exposed mice as well as with data from uninfected, unexposed mice. Oral administration of malathion to mice infected with 20, 40 or 60 S. mansoni cercariae adversely affect architecture of liver and spleen and critically alter hematological, biochemical, histological and hepatic enzymes parameters significantly more than the controls. Alterations observed in infected, exposed mice included (i) higher mortality rate; (ii) severe pathologies in liver and spleen; (iii) increased serum level of bilirubin and alanine aminotransferase/aspartate aminotransferase (ALT/AST) enzymes; (iv) decreased serum level of albumin and total proteins; and (v) decreased red blood cell count (RBC), lymphocytes, leucocytic count, and hemoglobin content. The number of recovered adult worms of S. mansoni or their oviposition capacity did not seem to be affected with malathion treatment. Statistical analysis revealed that the increase alteration in hepatic functions is correlated with increasing the number of S. mansoni cercariae and malathion doses. Such alterations were more significant in mice treated with the higher dose of malathion or infected with the largest numbers of S. mansoni cercariae. These data indicate that schistosomiasis can be exacerbated by simultaneous malathion exposure, which in turn adversely impact the clinical and pathological outcome of the disease. | 18,722,991 |
Elimination of keratin artifact bands from western blots by using low concentrations of reducing agents. | We encountered beta-mercaptoethanol-dependent artifact signals in western blot analyses using polyclonal antisera. Replacing beta-mercaptoethanol with dithiothreitol in the loading buffer did not eliminate the artifact signals. However, lowering the concentration of either dithiothreitol or beta-mercaptoethanol eliminated the background problems and allowed specific detection of the target protein. These results are consistent with the background signal being caused by anti-keratin antibodies in the antisera and keratin contamination of reagents. This study highlights the importance of testing a range of reducing agent concentrations when trying to eliminate artifact bands from western blots. However, this method may not be applicable when target proteins have disulfide bridges. | 18,722,995 |
Technique for cryopreservation of intestinal smooth muscle cells. | Attempts were made to develop a simplified procedure for long-term cryopreservation of intestinal smooth muscle cells (ISMC). ISMC were collected from the ileum of Sprague-Dawley neonatal rats through cellular dissociation in trypsin. Cryopreservation method comprised of a rapid 1-step (protocol 1) and a slow 3-step (protocol 2) freezing of ISMC for 1week. Preparations were thawed and single ISMC were assessed via the comet assay and damaged DNA was quantified through comet tail moment. The control unfrozen ISMC exhibited DNA damage of 2.34+/-0.35 compared to ISMC cooled via protocol 2 (2.62+/-0.36) and protocol 1 (10.15+/-0.72). Thereafter, protocol 2 freezing method was adopted and ISMC were cryopreserved for 1-week, 1-month, and 4-months to analyse the temporal and long-term cryopreservation of ISMC. This revealed a DNA damage of 2.62+/-0.36 (1-week), 3.81+/-0.72 (1-month), and 5.1+/-0.9 (4-months). Gradual cooling is suitable for continuing storage of ISMC and although fluctuation in cryoinjury is observed with time this is considered to reflect cell-to-cell variability. | 18,723,010 |
A dosage-dependent requirement for Sox9 in pancreatic endocrine cell formation. | We have previously shown the transcription factor SOX9 to be required for the maintenance of multipotential pancreatic progenitor cells in the early embryonic pancreas. However, the association of pancreatic endocrine defects with the Sox9-haploinsufficiency syndrome campomelic dysplasia (CD) implies additional later roles for Sox9 in endocrine development. Using short-term lineage tracing in mice, we demonstrate here that SOX9 marks a pool of multipotential pancreatic progenitors throughout the window of major cell differentiation. During mid-pancreogenesis, both endocrine and exocrine cells simultaneously arise from the SOX9(+) epithelial cords. Our analysis of mice with 50%-reduced Sox9 gene dosage in pancreatic progenitors reveals endocrine-specific defects phenocopying CD. By birth, these mice display a specific reduction in endocrine cell mass, while their exocrine compartment and total organ size is normal. The decrease in endocrine cells is caused by reduced generation of endocrine progenitors from the SOX9(+) epithelium. Conversely, formation of exocrine progenitors is insensitive to reduced Sox9 gene dosage, thus explaining the normal organ size at birth. Our results show that not only is SOX9 required for the maintenance of early pancreatic progenitors, but also governs their adoption of an endocrine fate. Our findings therefore suggest that defective endocrine specification might underlie the pancreatic phenotype of individuals with CD. | 18,723,011 |
Cataracts in transgenic mice caused by a human papillomavirus type 18 E7 oncogene driven by KRT1-14. | Human papillomavirus type 18 (HPV18) is a common cause of cervical cancer. To create a mouse model for this common neoplastic disease, we used a human keratin 14 promoter to drive the HPV18 E7 oncogene to create transgenic mice. No mice up to a year of age developed cervical cancer. However, all transgenic mice and none of the controls developed progressive bilateral cortical cataracts. By 6 months of age, the cortex liquefied leaving the lens nucleus. Proliferation of lens epithelium formed multifocal nodules and free floating lens epithelial cells within the liquefied cortex. These cells were hyperplastic not neoplastic. Other HPV transgenic stocks develop cataracts suggesting this virus may have a broad cellular tropism. | 18,723,014 |
The benzene metabolite trans,trans-muconaldehyde blocks gap junction intercellular communication by cross-linking connexin43. | Benzene is used at large volumes in many different human activities. Hematotoxicity and cancer-causation as a result of benzene exposure was recognized many years ago, but the mechanisms involved remain unclear. Aberrant regulation of gap junction intercellular communication (GJIC) has been linked to both cancer induction and interference with normal hematopoietic development. We have previously suggested that inhibition of GJIC may play a role in benzene toxicity since benzene metabolites were found to block GJIC, the ring-opened trans,trans-muconaldehyde (MUC) being the most potent metabolite. In the present work we have studied the molecular mechanisms underlying the MUC-induced inhibition of gap junctional communication. We show that MUC induces cross-linking of the gap junction protein connexin43 and that this is likely to be responsible for the induced inhibition of GJIC, as well as the loss of connexin43 observed in Western blots. We also show that glutaraldehyde possesses similar effects as MUC, and we compare the effects to that of formaldehyde. The fact that glutaraldehyde and formaldehyde have been associated with induction of leukemia as well as disturbance of hematopoiesis, strengthens the possible link between the effect of MUC on gap junctions, and the toxic effects of benzene. | 18,723,040 |
Bothrops jararaca venom (BjV) induces differential leukocyte accumulation in mice genetically selected for acute inflammatory reaction: the role of host genetic background on expression of adhesion molecules and release of endogenous mediators. | The dynamics of the local inflammatory events induced by Bothrops jararaca venom (BjV) inoculation in footpad of mice genetically selected for maximal (AIRmax) and minimal (AIRmin) acute inflammatory reactivity (AIR) was investigated. The BjV injection induced a marked inflammatory cell infiltrate with predominance of neutrophils, with increased blood cell numbers before its accumulation, suggesting a stimulatory action of BjV on mechanisms of cell mobilization from bone marrow. The process of cell migration is regulated by different cell-adhesion molecules (CAM). Our results showed that neutrophil cells from both lines had the same pattern of response concerning CAMs expression, presenting the involvement of l-selectin, Mac-1 and PECAM-1 adhesion molecules in BjV-induced neutrophil accumulation. The effect of BjV on the release of pro-inflammatory cytokines and chemokines related with cellular migration was also studied and IL-1beta, IL-6, TNF-alpha and MIP-2 levels could be detected after venom injection. The AIRmax mice were shown to be more responsive than AIRmin with respect to leukocyte influx, expression of MIP-2 and release of IL-1beta and IL-6. These results demonstrate the importance of host genetic background in the local response and the involvement of alleles accumulated in AIRmax mice in the inflammatory events induced by BjV. | 18,723,041 |
Steroid-converting enzymes in human ovarian carcinomas. | Anti-estrogen therapies for treating ovarian carcinoma have had mixed outcomes suggesting some tumors may be estrogen-dependent. We assayed the activity levels of 17beta-hydroxysteroid dehydrogenase (17beta-HSD), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD/3-KSR) and estrone sulfatase in a series of ovarian epithelial carcinomas. 17beta-HSD activity ratios with estradiol (E(2)) and testosterone (T), and inhibition by isoform-specific inhibitors were used to estimate the contributions of 17beta-HSD isoforms. Activity levels were highest for estrone sulfatase, followed, respectively by 17beta-HSD, 3alpha-HSD/3-KSR, and 3beta-HSD. E(2)/T activity ratios varied widely between samples. A 17beta-HSD type 1 inhibition pattern was observed in 23% of the samples and a type 2 pattern in 25%. E(2) formation from estrone sulfate (E(1)S) was detected in 98% (47/48) of the samples. 17beta-HSD type 1, type 2 and type 5 mRNA was detected in matched primary tumor and metastases. Evaluation of 17beta-HSD and sulfatase activity levels, activity ratios and inhibition patterns may help predict tumor response to endocrine therapy. | 18,723,074 |
Positive circuits and d-dimensional spatial differentiation: application to the formation of sense organs in Drosophila. | We discuss a rule proposed by the biologist Thomas according to which the possibility for a genetic network (represented by a signed directed graph called a regulatory graph) to have several stable states implies the existence of a positive circuit. This result is already known for different models, differential or discrete formalism, but always with a network of genes contained in a single cell. Thus, we can ask about the validity of this rule for a system containing several cells and with intercellular genetic interactions. In this paper, we consider the genetic interactions between several cells located on a d-dimensional lattice, i.e., each point of lattice represents a cell to which we associate the expression level of n genes contained in this cell. With this configuration, we show that the existence of a positive circuit is a necessary condition for a specific form of multistationarity, which naturally corresponds to spatial differentiation. We then illustrate this theorem through the example of the formation of sense organs in Drosophila. | 18,723,072 |
Haeme oxygenase and nitric oxide synthetase blockade and brain blood flow in sheep exposed to carbon monoxide. | Carbon monoxide (CO) usually does not damage the brain cortex in our in vivo model. To investigate the possible protective role of responsive and regulated changes in blood flow, 24 ewes were randomly assigned in equal numbers to sham-control, CO-control and treatment (haeme oxygenase (HO) and nitric oxide synthetase (NOS) inhibited) groups. Sheep in the second and third groups were then anaesthetised with CO for 2 h. Brain blood flow was measured using Laser Doppler and was increased in CO exposed sheep. The CO-induced anaesthesia was associated with isolated brain white matter damage. In the HO/NOS inhibited sheep, cortical EEG recovery after the anaesthesia was slower and incomplete, and cortical blood flow increased whereas white matter flow decreased. These results confirm our earlier findings that the induction of HO and NOS by CO inhalation is protective, but, suggest a relationship between tissue injury and blood flow that is perhaps partly causal. | 18,723,078 |
Characterization of water of hydration fractions in rabbit skeletal muscle with age and time of post-mortem by centrifugal dehydration force and rehydration methods. | Centrifugal dehydration force (CDF) and rehydration isotherm (RHI) methods were used to measure and characterize hydration fractions in rabbit psoas skeletal muscle. The CDF method assessed fluid flow rate from rabbit muscle and hydration capacity of the fractions. Bulk and multiple non-bulk water fractions were identified. The non-bulk water was divisible into the following fractions: two outer non-bulk fractions, a main chain proteins backbone or double water bridge fraction, and a single water bridge fraction. The total non-bulk water amounts to about 85% of the total water in the muscle. The sizes of the water fractions (in g water/g dry mass) agree with a recently proposed molecular stoichiometric hydration model (SHM) applicable to all proteins in and out of cells (Fullerton GD, Cameron IL. Water compartments in cells. Methods Enzymol, 2007; Cameron IL, Fullerton GD. Interfacial water compartments on tendon/collagen and in cells. In: Pollack GH, Chin WC, editors. Phase transitions in cells. Dordrecht, The Netherlands: Springer, 2008). Age of the rabbit significantly slowed the flow rate of the outer non-bulk water fraction by about 50%. Also, muscle of the older rabbit (26 weeks vs. 12 weeks old) had less bulk water and less outer non-bulk water but the same amount of main chain backbone water compared to muscle of the younger rabbit. Increase in time post-mortem from 30min to 4h resulted in rigor mortis and a significantly slower flow rate of water from the outer non-bulk water fraction, which is attributed to muscle contraction, increased packing of contractile elements and increased obstructions to flow of fluid from the muscle fibers. | 18,723,101 |
Teneurins: important regulators of neural circuitry. | Teneurin (Ten-m/Odz) molecules represent a highly conserved family of four type II transmembrane proteins in vertebrates (Ten-m1-4), which exist as homodimers and undergo homophilic interactions. Each is expressed in distinct, and often interconnected, areas of the developing nervous system. Different Ten-ms have complementary expression patterns. In vitro and in vivo studies support roles for teneurins in promoting neurite outgrowth and cell adhesion. Furthermore, the intracellular domains of at least two teneurins can undergo proteolytic cleavage and translocate to the nucleus where they regulate transcriptional activity. Recent in vivo studies show that teneurins play important roles in regulating connectivity in the nervous system. Knockdown in C. elegans resulted in abnormal axon guidance and cell migration, while targeted deletion of Ten-m3 in mice revealed it is required for the guidance of retinal axons and generation of visual topography. It is likely that all teneurins play important roles during neural development. | 18,723,111 |
RAP55: insights into an evolutionarily conserved protein family. | The RAP55 protein family is evolutionarily conserved in eukaryotes. Two highly conserved paralogues, RAP55A and RAP55B, exist in vertebrates; their functional properties and expression patterns remain to be compared. RAP55 proteins share multiple domains: the LSm14 domain, a serine/threonine rich region, an FDF (phenylalanine-aspartate-phenylalanine) motif, an FFD-TFG box and RGG (arginine-glycine-glycine) repeats. Together these domains are responsible for RAP55 proteins participating in translational repression, incorporation into mRNP particles, protein-protein interactions, P-body formation and stress granule localisation. All RAP55A proteins localise to P-body-like complexes either in the germline or in somatic cells. Xenopus laevis RAP55B has been shown to be part of translationally repressed mRNP complexes in early oocytes. Together these findings suggest that this protein family has evolved a common and fundamental role in the control of mRNA translation. Furthermore human RAP55A is an autoantigen detected in the serum of patients with primary biliary cirrhosis (PBC). The link between RAP55A, P-bodies and PBC remains to be elucidated. | 18,723,115 |
On the prevalence of bipolar disorder in epilepsy. | Although mood disorders represent a frequent psychiatric comorbidity in epilepsy, data on bipolar disorder (BD) are still limited, and the role of possible specific confounding variables (seizures and antiepileptic drug therapy) has never been considered. Data for 143 adult outpatients with epilepsy assessed with the Mini International Neuropsychiatric Interview Plus Version 5.0.0 using the Epilepsy Addendum for Psychiatric Assessment, the Mood Disorder Questionnaire, and the Interictal Dysphoric Disorder Inventory revealed that 11.8% had the Diagnostic and Statistical Manual of Mental Disorders-based diagnosis of BD, only 1.4% of whom could be considered as having "pure" BD, because in all other cases BD symptoms were related to phenotype copies of BD such as interictal dysphoric disorder of epilepsy, postictal manic or hypomanic states, and preictal dysphoria. | 18,723,118 |
Aberrant T cell ERK pathway signaling and chromatin structure in lupus. | Human systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibodies to nuclear components with subsequent immune complex formation and deposition in multiple organs. A combination of genetic and environmental factors is required for disease development, but how the environment interacts with the immune system in genetically predisposed hosts to cause lupus is unclear. Recent evidence suggests that environmental agents may alter T cell chromatin structure and gene expression through effects on DNA methylation, a repressive epigenetic mechanism promoting chromatin inactivation, to cause lupus in people with the appropriate genetic background. DNA methylation is regulated by ERK pathway signaling, and abnormalities in ERK pathway signaling may contribute to immune dysfunction in lupus through epigenetic effects on gene expression. This article reviews current evidence for epigenetic abnormalities, and in particular DNA demethylation, in the pathogenesis of idiopathic and some forms of drug-induced lupus, and how impaired ERK pathway signaling may contribute to the development of human lupus through effects on T cell DNA methylation. | 18,723,128 |
Differential expression of microRNA species in organs of hibernating ground squirrels: a role in translational suppression during torpor. | Mammalian hibernation includes long periods of profound torpor where the rates of all metabolic processes are strongly suppressed in a reversible manner. We hypothesized that microRNAs (miRNAs), small non-coding transcripts that bind to mRNA, could play a role in the global suppression of mRNA translation when animals enter torpor. Selected miRNA species (4-9 of the following: mir-1, mir-24, mir-15a, mir-16, mir-21, mir-122a, mir-143, mir-146 and mir-206) were evaluated in four organs of euthermic versus hibernating ground squirrels, Spermophilus tridecemlineatus using RT-PCR. Levels of mir-24 transcripts were significantly reduced in heart and skeletal muscle of torpid animals as were mir-122a levels in the muscle. Mir-1 and mir-21 both increased significantly in kidney during torpor by 2.0- and 1.3-fold, respectively. No changes were found for the four miRNA species analyzed in liver. Protein levels of Dicer, an enzyme involved in miRNA processing were also quantified in heart, kidney and liver. Dicer protein levels increased by 2.7-fold in heart during hibernation but decreased by 60% in kidney. These data are the first report that differential regulation of miRNA levels occurs during mammalian hibernation and they provide a mechanism for reversible gene silencing during torpor that can be rapidly reversed to allow renewed translation of mRNA when animals arouse back to euthermia. | 18,723,136 |
Effect of blinking on tear volume after instillation of midviscosity artificial tears. | To determine by optical coherence tomography (OCT) the effect of blinking on ocular surface tear volume after instillation of artificial tears. Experimental study. Normal human eyes (n = 21) were imaged to obtain dimensions of the tear film and menisci during blinking. The imaging was carried out immediately and five minutes after the instillation of 35 microl midviscosity artificial tears (1.0% carboxymethylcellulose; Refresh Liquigel; Allergan, Irvine, California, USA). The exposed ocular surface area and the lid lengths were used to calculate the volumes. Immediately after the instillation, total tear volume was increased (P < .001) compared with five minutes after the instillation, with the major increases in the lower tear meniscus volume and tear film volume. After the instillation, blinking caused tear loss in total tear volume because of the decrease of the lower tear meniscus volume (P < .05). In contrast, blinking increased the tear film volume (P < .05). At the end of the eye-opening period, tear film volume decreased and lower tear meniscus volume increased significantly (P < .05), with no significant changes in total tear volume (P > .05). During the blink cycle immediately after the instillation, net loss was evident in tear film volume, lower tear meniscus volume, and total tear volume (P < .05). Blinking plays a crucial role in distribution and removal of instilled tears. When the tear system is overloaded, the increase in blink output helps restore balance. | 18,723,145 |
Factors associated with delayed postsurgical voiding interval in ambulatory spinal anesthesia patients: a prospective cohort study in 3 types of surgery. | Spinal anesthesia has been considered inappropriate for ambulatory surgery patients because of concern about voiding dysfunction. The purpose of this study was to analyze the relationship between voiding interval and type of surgery under spinal anesthesia with lidocaine and to identify other nonanesthetic risk factors for delayed voiding. A prospective study of 406 patients undergoing to ambulatory surgery under spinal anesthesia with lidocaine was performed. Voiding interval was defined as the time in minutes from the injection of local anesthetic to the patient's first spontaneous voiding. Univariate and multivariate linear regression models were constructed to identify risk factors associated with length of voiding interval. A total of 187 patients underwent herniorrhaphy; 187 patients underwent lower limb surgery; and 32 patients went benign anorectal surgery. The mean +/- sd voiding interval was 230 +/- 50.5 minutes. Factors associated with length of voiding interval in the univariate analysis were sex, body mass index (BMI), type and duration of surgery, lidocaine dose, and volume of fluid administered. Factors that remained significant in the multivariate model were sex, BMI, lidocaine dose and type of surgery: spontaneous voiding came later after inguinal herniorrhaphy surgery than after lower-limb surgery (regression coefficient 20 minutes; 95% confidence interval 11.5-29.8). Multivariate models performed for each type of surgery separately identified sex and lidocaine dose as factors related to length of voiding interval in all types of surgery. A longer voiding interval was associated with inguinal herniorrhaphy, spinal lidocaine dose, and male sex. | 18,723,151 |
Scientific Impact Recognition Award: Molecular breast imaging: a review of the Mayo Clinic experience. | Molecular breast imaging (MBI) depicts functional uptake of targeted radiotracers in the breast using dedicated gamma cameras. MBI studies were performed under several institutional protocols evaluating the use of MBI in screening and diagnosis. By using a single-head system, sensitivity for breast cancer detection was 85% (57 of 67) overall and 29% for tumors 5 mm or less in diameter. Sensitivity improved to 91% (117 of 128) overall and 69% for tumors 5 mm or less using a dual-head system. In 650 high-risk patients undergoing breast cancer screening, MBI detected 7 cancers, 5 of which were missed on mammography. In 24 of 149 (16%) breast cancer patients MBI detected additional disease not seen on mammography. The sensitivity of MBI was 88% (83 of 94) for invasive ductal carcinoma, 79% (23 of 29) for invasive lobular carcinoma, and 89% (25 of 28) for ductal carcinoma in situ. MBI can detect invasive ductal carcinoma, ductal carcinoma in situ, and invasive lobular carcinoma. It has a promising role in evaluating the extent of disease and multifocal disease in the breast for surgical treatment planning. | 18,723,155 |
Combining early markers strongly predicts conversion from mild cognitive impairment to Alzheimer's disease. | The utility of combining early markers to predict conversion from mild cognitive impairment (MCI) to Alzheimer's Disease (AD) remains uncertain. Included in the study were 148 outpatients with MCI, broadly defined, followed at 6-month intervals. Hypothesized baseline predictors for follow-up conversion to AD (entire sample: 39/148 converters) were cognitive test performance, informant report of functional impairment, apolipoprotein E genotype, olfactory identification deficit, and magnetic resonance imaging (MRI) hippocampal and entorhinal cortex volumes. In the 3-year follow-up patient sample (33/126 converters), five of eight hypothesized predictors were selected by backward and stepwise logistic regression: Pfeffer Functional Activities Questionnaire (FAQ; informant report of functioning), University of Pennsylvania Smell Identification Test (UPSIT; olfactory identification), Selective Reminding Test (SRT) immediate recall (verbal memory), MRI hippocampal volume, and MRI entorhinal cortex volume. For 10% false positives (90% specificity), this five-predictor combination showed 85.2% sensitivity, combining age and Mini-Mental State Examination (MMSE) showed 39.4% sensitivity; combining age, MMSE, and the three clinical predictors (SRT immediate recall, FAQ, and UPSIT) showed 81.3% sensitivity. Area under ROC curve was greater for the five-predictor combination (.948) than age plus MMSE (.821; p = .0009) and remained high in subsamples with MMSE > or = 27/30 and amnestic MCI. The five-predictor combination strongly predicted conversion to AD and was markedly superior to combining age and MMSE. Combining the clinically administered measures also led to strong predictive accuracy. If independently replicated, the findings have potential utility for early detection of AD. | 18,723,162 |
Preparative isolation and purification of two benzoxazinoid glucosides from Acanthus ilicifolius L. by high-speed counter-current chromatography. | The first preparative separation of two benzoxazinoids, (2R)-2-O-beta-d-glucopyranosyl-2H-1,4-benzoxazin-3(4H)-one (HBOA-Glc) and (2R)-2-O-beta-d-glucopyranosyl-4-hydroxy-2H-1,4-benzoxazin-3(4H)-one (DIBOA-Glc), by means of high-speed counter-current chromatography (HSCCC) from the n-butanol extract of Acanthus ilicifolius L. is presented. The two-phase solvent system containing ethyl acetate-n-butanol-0.5%NH(4)OH (2:3:5, v/v/v, system B) was selected for the one-step HSCCC separation of HBOA-Glc and DIBOA-Glc according to the partition coefficient values (K) for target compounds and the separation factor (alpha) between the two target compounds. In the one-step HSCCC separation using solvent B, from 100mg n-butanol extract of A. ilicifolius, 6.3 mg HBOA-Glc and 6.8 mg DIBOA-Glc were isolated with purities of 90.3% and 80.2%, respectively. In order to obtain the two target compounds with higher purity, a second separation process was developed comprising two steps. In the two-step separation, the sample was first pre-purified by HSCCC using ethyl acetate-n-butanol-water (2:3:5, v/v/v, system A) solvent system and then purified using solvent system B. A 100-mg amount of the n-butanol extracts of A. ilicifolius was separated to yield 5.8 mg of HBOA-Glc and 4.8 mg of DIBOA-Glc with purities of 97.1% and 94.8%, respectively, which were directly used for NMR analyses. | 18,723,179 |
Controlled deposition of calcium carbonate particles on porous membranes by using alternating current system. | The deposition of calcium carbonate particles in the absence of additives was performed through the application of an alternating current. Solutions of calcium chloride and sodium carbonate were filled in glass cells, and a porous polymer membrane was interposed between the glass cells. An alternating current with a sine waveform (frequency: 10 Hz) was applied by using a platinum electrode. In this process, the reciprocal migration of calcium and carbonate ions toward the interface of the pores on the membrane takes place. Moreover, ion mixing occurs to a small extent at the interface of the pores. An alternating current was applied for 30 min during which the ion mixing continued. When observed using a scanning electron microscope, a majority of the formed calcium carbonate particles was found to exhibit a spheroidal vaterite crystal structure. This crystal structure was confirmed to be vaterite after characterization by X-ray diffraction. In the absence of an alternating current, only calcite was formed on the porous polymer membrane. Taking this result into account, it was concluded that the alternating current could induce reciprocal ion migration through the pores of the membrane, and vaterite deposition can be achieved. This is one of the methods employed for the calcium carbonate formation on the porous membrane by using an alternating current system. | 18,723,181 |
Analysis of compositional data in communication disorders research. | The study of communication and its disorders often involves coding several behaviors and examining the proportions with which individual behaviors are produced within data sets. Problems are encountered when studying multiple behaviors between data sets, because of the interdependence of the proportions: as one coded behavior increases, at least one other must decrease. The interdependence of data means that traditional statistical techniques can be used to analyse differences in the proportion of only one behavior over time or between clinical groups. We describe a statistical technique, previously used in geological and biomedical research, which can be used to analyse all behaviors in compositional data sets, and give examples of its use with interaction data. The technique allows, for the first time, full comparison of entire patterns of multiple communication behaviors, both over time and between clinical groups. The technique will aid both basic and applied communication research. Readers will understand the advantages and limitations of frequency counts and proportions for the analysis of multiple behaviors. Readers will be able to analyze change in proportions of multiple behaviors within a data set between groups and across time. | 18,723,184 |
Prognostic significance of inverse spatial QRS-T angle circadian pattern in myocardial infarction survivors. | We investigated the predictive value of the spatial QRS-T angle (QRSTA) circadian variation in myocardial infarction (MI) patients. Analyzing 24-hour recordings (SEER MC, GE Marquette) from 151 MI patients (age 63 +/- 12.7), the QRSTA was computed in derived XYZ leads. QRS-T angle values were compared between daytime and night time. The end point was cardiac death or life-threatening ventricular arrhythmia in 1 year. Overall, QRSTA was slightly higher during the day vs. the night (91 degrees vs. 87 degrees, P = .005). However, 33.8% of the patients showed an inverse diurnal QRSTA variation (higher values at night), which was correlated to the outcome (P = .001, odds ratio 6.7). In multivariate analysis, after entering all factors exhibiting univariate trend towards significance, inverse QRSTA circadian pattern remained significant (P = .036). Inverse QRSTA circadian pattern was found to be associated with adverse outcome (22.4%) in MI patients, whereas a normal pattern was associated (96%) with a favorable outcome. | 18,723,188 |
Antitumoral and antileishmanial dioncoquinones and ancistroquinones from cell cultures of Triphyophyllum peltatum (Dioncophyllaceae) and Ancistrocladus abbreviatus (Ancistrocladaceae). | From the methanolic extracts of solid callus cultures from two species of the closely related palaeotropical plant families Dioncophyllaceae and Ancistrocladaceae seven new natural naphthoquinones were isolated, dioncoquinones A (4) and B (5) from Triphyophyllum peltatum, and ancistroquinones B (6), C (7), D (9), E (10), and F (12) from Ancistrocladus abbreviatus. Their structures were elucidated by spectroscopic, chemical, and computational methods. Furthermore, the already known naphthoquinones plumbagin (2), droserone (3), malvone A (8), and nepenthone A (11) were found in the extract of A. abbreviatus. Dioncoquinones A (4) and B (5) showed good - and specific - activity against Leishmania major, while they were not active against other protozoic parasites. Moreover, treatment with 4 and 5 strongly induced apoptosis in human tumor cells derived from two different B cell malignancies, B cell lymphoma and multiple myeloma, without any significant toxicity towards normal peripheral mononuclear blood cells. | 18,723,197 |
Polymer biodegradation: mechanisms and estimation techniques. | Within the frame of the sustainable development, new materials are being conceived in order to increase their biodegradability properties. Biodegradation is considered to take place throughout three stages: biodeterioration, biofragmentation and assimilation, without neglect the participation of abiotic factors. However, most of the techniques used by researchers in this area are inadequate to provide evidence of the final stage: assimilation. In this review, we describe the different stages of biodegradation and we state several techniques used by some authors working in this domain. Validate assimilation (including mineralisation) is an important aspect to guarantee the real biodegradability of items of consumption (in particular friendly environmental new materials). The aim of this review is to emphasise the importance of measure as well as possible, the last stage of the biodegradation, in order to certify the integration of new materials into the biogeochemical cycles. Finally, we give a perspective to use the natural labelling of stable isotopes in the environment, by means of a new methodology based on the isotopic fractionation to validate assimilation by microorganisms. | 18,723,204 |
Absorption of nitro-polycyclic aromatic hydrocarbons by biomembrane models: effect of the medium lipophilicity. | To demonstrate the relationship between the structure of nitro-polycyclic aromatic hydrocarbons and their effect on biomembranes, we have investigated the influence of three structurally different nitro-polycyclic aromatic hydrocarbons, 2-nitrofluorene, 2,7-dinitrofluorene and 3-nitrofluoranthene, on the thermotropic behavior of dimyristoylphosphatidylcholine multilamellar vesicles, used as biomembrane models, by means of differential scanning calorimetry. The obtained results indicate that the studied nitro-polycyclic aromatic hydrocarbons affected the thermotropic behavior of multilamellar vesicles to various extents, modifying the pretransition and the main phase transition peaks and shifting them to lower temperatures. The effect of the aqueous and lipophilic medium on the absorption process of these compounds by the biomembrane models has been also investigated revealing that the process is hindered by the aqueous medium but strongly allowed by the lipophilic medium. | 18,723,205 |
Muscle sympathetic nerve activity in patients with Chagas' disease. | The progression of heart failure in Chagas' disease has been explained by remodeling, leading to neurohumoral activation, or by the direct parasite damage to parasympathetic neurons during acute phase, leading to early sympathetic activation and progressive heart failure. To help distinguish between these hypotheses we studied muscle sympathetic nerve activity (MSNA) at rest and during handgrip exercise (30% of maximal voluntary contraction) in patients with Chagas' disease and normal ejection fraction vs. patients with heart failure. A consecutive study of 72 eligible out-patients/subjects was conducted between July 1998 and November 2004. The participants were classified in three advanced heart failure groups (New York Heart Association Functional Classes II-III): Chagas' disease (n=15), ischemic (n=15) and idiopathic cardiomyopathy (n=15). Twelve Chagas' disease patients without heart failure and normal ejection fraction, and 15 normal controls were also studied. MSNA was recorded directly from the peroneal nerve by microneurography technique. MSNA was greater in heart failure patients when compared with Chagas' disease patients without heart failure (51+/-3 vs. 20+/-2 bursts/min P=0.0001). MSNA in Chagas' patients with normal ejection fraction and normal controls was not different. During exercise, MSNA was similar in all 3 heart failure groups. And, was lower in the Chagas' patients with normal ejection fraction than in patients with Chagas' disease and heart failure (28+/-1 vs. 63+/-5 bursts/min, respectively). MSNA is not elevated in patients with Chagas' disease with normal ejection fraction. These findings support the concept of remodeling and neurohumoral activation as a common pathway following significant cardiac injury. | 18,723,231 |
Adsorption characteristics of As(V) on iron-coated zeolite. | The sorption characteristics of arsenic(As(V)) on iron-coated zeolite (ICZ) were investigated through batch and column studies. As(V) was completely removed within 30 min in a concentration of 2mg/l, with a 100g/l dose of ICZ. Optimum dose of ICZ was 33.3g/l at a concentration of 20.12 mg/l and the effect of solution pH was negligible at a pH range of 3.0<pH<10.0. Langmuir Isotherm Model was suitable to explain the sorption characteristics of As(V) onto ICZ. The co-presence of sulfate ions inhibited sorption of As(V) because of competitive adsorption. The adsorption capacity of ICZ for As(V) was 0.68 mg/g. Based on the result, ICZ is a suitable material to treat the mine drainage or wastewater bearing As(V). | 18,723,277 |
Patient-provider communication and cancer screening among unmarried women. | Unmarried women are less likely than married women to receive recommended cancer screenings. Patient-provider communication is a consistent predictor of cancer screening among women. The purpose of this study was to investigate the relationship between patient and provider communication, barriers to cancer screening, and on-schedule breast and cervical cancer screening (BCCS) among unmarried women. Data were from the Cancer Screening Project for Women, a 2003-2005 survey examining cancer screening practices. We computed polytomous logistic regression models to examine the relationship between communication (communication about tests, communication about sexual and intimate relationships), barriers to screening, and on-schedule BCCS among unmarried women. A total of 630 women were enrolled, and 605 women completed the baseline questionnaire. Overall, more than 60% reported on-schedule BCCS. More than half reported that their providers communicated about BCCS most or all of the time. Fewer than half communicated about sexual history and intimate relationships. Women who reported that their providers communicated about screening tests and their sexual and intimate relationships were more likely to be on-schedule for BCCS. Patient-provider communication about multiple topics may encourage women to remain on-schedule for their recommended cancer screenings. Longitudinal research should be conducted to examine whether communication predicts BCCS, and to examine how patient and provider characteristics may influence communication in order to promote adherence to screening guidelines for unmarried women. Comprehensive communication that goes beyond information about screening tests may impact adherence to cancer screening guidelines. | 18,723,307 |
Application of quantitative tissue velocity imaging to evaluate left ventricular early diastolic dysfunction in dogs with heart failure due to rapid ventricular pacing. | The authors assessed the capability of quantitative tissue velocity imaging (QTVI) to detect left ventricular (LV) early diastolic dysfunction (LVEDDY) in a canine model. Rapid ventricular pacing (RVP) at 240 beats/min was maintained in 14 dogs for 2 weeks. Echocardiography, cardiac catheterization, and endomyocardial biopsies were performed at baseline, during pacing, and at 2 weeks. QTVI, conventional echocardiographic, and LV pressure and pathologic indices were measured, and correlations were analyzed during the progressive development of diastolic dysfunction produced by RVP. Receiver operating characteristic (ROC) curves of QTVI parameters were analyzed to identify predictors of LVEDDY. The onset of LVEDDY occurred 24 hours after RVP initiation. Most of the QTVI indices were altered at 12 or 24 hours after RVP onset. New parameters were identified, including time-R and time-E', which are the times from aortic valve closure to peak isovolumetric relaxation (R) and peak early diastolic velocity (E'), respectively, as well as the ratios of peak myocardial systolic velocity (S') and peak E' to R (S'/R and E'/R, respectively), which significantly changed during RVP. These parameters were correlated with LV -dp/dt(max) or LV end-diastolic pressure, but time-R, time-E', and S'/R were not correlated with heart rate. In addition, using ROC analysis, time-R had the largest area under the curve to predict LVEDDY after RVP. QTVI is a sensitive and specific quantitative method that can be used for the early detection of LVEDDY under tachycardic conditions. The novel indices described here, including time-R, time-E', and S'/R, can serve as effective, noninvasive, possibly heart rate independent LVEDDY markers. | 18,723,320 |
Role of surfactants in optimizing fluorene assimilation and intermediate formation by Rhodococcus rhodochrous VKM B-2469. | Biodegradation of fluorene by Rhodococcus rhodochrous VKM B-2469 was investigated and optimized by adding non-ionic surfactants to the liquid media. The utilization of 1-1.5% Tween 60 or 1% Triton X100 allowed to solubilize 1 mM fluorene over 150 times more than in water medium (from 9-11 microM to above 1.5 mM at 28 degrees C). We observed that Tween 60 was useful to enhance the fluorene biodegradation rates further supporting R. rhodochrous VKM B-2469 growth as an additional carbon source and to decrease fluorene toxicity for bacterial cells whereas Triton X100 resulted to be toxic for this strain. An additional enzyme induction step before starting the bioconversion process and the increase of incubation temperature during fluorene bioconversion led to further improvements in rates of fluorene utilization and formation of its intermediates. In the optimized conditions 1 mM fluorene was degraded completely within 24h of incubation. Some intermediates in fluorene degradation built up during the process reaching maxima of 31% for 9-hydroxyfluorene, 2.1% for 9-fluorenone and 1.9% for 2-hydroxy-9-fluorenone (starting from 1 mM substrate). In the presence of Tween 60 the appearance and following conversion of 2-hydroxy-9-fluorenone was observed for R. rhodochrous VKM B-2469 revealing the existence of a new pathway of 9-fluorenone bioconversion. | 18,723,343 |
Cyclic diarylheptanoids from Myrica nana inhibiting nitric oxide release. | Investigation of the roots of Myrica nana afforded five new cyclic diarylheptanoids, myricananins A-E (1-5), two new artifacts of myricananins A and B (6-7), and four known compounds, 12-hydroxymyricanone (8), alnusonol (9), myricatomentogenin (10), and actinidione (11). The structures of these new compounds were established by detailed spectroscopic methods. The stereochemistry of compounds 1 and 2 were determined by single-crystal X-ray diffraction. In exception of compounds 2, 6 and 10, all the other compounds were examined for their inhibitory effects on nitric oxide production in lipopolysaccharides-activated macrophages. Compounds 1, 3, 7, 8 and 9 inhibited the release of nitric oxide with IC(50) values of 45.32, 63.51, 52.81, 30.19 and 46.18muM, respectively. Furthermore, compound 1 was found to inhibit the expression of inducible nitric oxide synthase. | 18,723,353 |
Patency rate of the internal thoracic artery to the left anterior descending artery bypass is reduced by competitive flow from the concomitant saphenous vein graft in the left coronary artery. | In coronary artery bypass grafting (CABG), insufficient bypass flow can be a cause of occlusion or string sign of the internal thoracic artery (ITA) graft. A patent saphenous vein (SV) graft from the ascending aorta can reduce the blood flow through the ITA graft, and may affect its long-term patency. In the present study, we examined the impact of the patent SV graft to the left coronary artery on the long-term patency of the ITA to left anterior descending (LAD) artery bypass. We reviewed the coronary angiograms of 313 patients who had two bypasses to the left coronary artery including 1 in situ ITA to LAD graft between March 1986 and December 2006. Patients who had occlusion of either bypass grafts to the left coronary artery in the early angiography, were excluded. In 64 patients (20.4%), bilateral ITAs were individually anastomosed to the LAD and the second target branch in the left coronary artery (BITA group), while 249 patients (79.6%) had the ITA to LAD bypass and the SV graft to the second target branch in the left coronary artery (ITA/SV group). The mean follow-up period was 6.8+/-4.9 years. The cumulative patency rate of ITA-LAD bypasses at 10 years was 100% in the BITA group and 81.4% in the ITA/SV group. The ITA to LAD bypass was occluded in 14 (5.6%) patients of the ITA/SV group. In the ITA/SV group, the cumulative graft patency rate of the ITA to LAD bypass in patients who had severe (> or =76%) native coronary stenosis between the two anastomotic sites was 98.6% at 5 years, and was significantly higher than that of 82.3% in patients without severe stenosis (p<0.0001). Long-term patency of the ITA-LAD bypass was affected by the presence of the patent SV graft to the left coronary artery, particularly when the native coronary stenosis between the two anastomotic sites was not severe. Competitive flow from SV graft could play an important role in occlusion of the in-situ arterial graft. | 18,723,364 |
Multidimensional geriatric assessment in treatment decision in elderly cancer patients: 6-year experience in an outpatient geriatric oncology service. | This prospective cohort study of consecutive elderly cancer patients was undertaken to evaluate the role of the multidimensional geriatric assessment (MGA) as an aid in treatment decision-making. A total of 571 cancer patients (aged > or =70) were enrolled during 6-year (1999-2005). All underwent MGA as part of the first evaluation. In multivariate analysis, the probability of receiving active, instead of palliative, treatment was negatively associated with increasing age (odds ratio=0.69 every 5 years, p=0.005), living alone (OR=0.54, p=0.031), dependence in activities of daily living (ADL score >0, OR=0.41, p=0.003) and a low body-mass index (BMI) (OR=0.51, p=0.061); while a positive association emerged for instrumental activities of daily living (IADL) score (OR=1.12 per point, p=0.019). Our data suggest that MGA, in addition to age, is a useful tool in clinical practice for deciding cancer treatment in elderly patients, with a major independent role played by living alone, ADL, IADL and BMI. | 18,723,367 |
Palonosetron plus dexamethasone effectively prevents acute and delayed chemotherapy-induced nausea and vomiting following highly or moderately emetogenic chemotherapy in pre-treated patients who have failed to respond to a previous antiemetic treatment: comparison between elderly and non-elderly patient response. | Aim of the present phase II non-randomized study was to verify whether palonosetron might be able to prevent acute and especially delayed CINV for either HEC or MEC, starting from the second chemotherapy cycle, in patients who had failed to respond to a different antiemetic 5-HT(3) antagonist during the first cycle. Stratification factor was age <65 years vs. > or =65 years of patients included. Forty-seven cancer patients (23 elderly and 24 non-elderly) scheduled to receive HEC or MEC regimens who had experienced CINV grade 3-4 during the first chemotherapy course and for whom the same course of chemotherapy regimen was further scheduled were enrolled. Complete response (CR) and complete control (CC) rates for the acute, delayed and overall phases of CINV were not significantly different between elderly and non-elderly patients. Palonosetron was safe: only grade 1-2 toxicities were observed with a peak of 12.9% for asthenia with no significant difference between elderly and non-elderly patients. In conclusion, single dose palonosetron (250 microg) should be considered a safe and effective second generation 5-HT(3) antagonist in the prevention of nausea and vomiting induced by HEC or MEC, irrespective of patients' age. | 18,723,369 |
Frequency and patterns of MRI abnormalities due to status epilepticus. | MRI changes due to status epilepticus (SE) often suggest a combination of cytotoxic and vasogenic edema, but it is unclear why only certain patients have MRI changes. To determine the frequency of MRI changes due to SE and the associated patient characteristics. We reviewed records for demographics, medical history, and MRI changes attributable to seizures of all patients admitted to Brigham and Women's Hospital or Massachusetts General Hospital for SE from 1/1999 to 7/2003 and who had MRI during admission. Ten (11.6%) of the eighty-six patients identified had MRI abnormalities likely due to seizures. Four, two with pre-existing epilepsy and two with extratemporal structural lesions, had focally increased signal on T2 and diffusion-weighted imaging (DWI) in the hippocampus ipsilateral to the seizure focus. One, with elevated levels of clozapine, had increased signal on T2 weighted images and variably restricted diffusion in the splenium. Five had gyral distribution of restricted diffusion and increased signal on T2 weighted images; they had complex medical comorbidities and possible hypoperfusion or hypoxia associated with SE. Among patients with SE who had MRI changes, those with previous epilepsy or extratemporal structural lesions showed increased diffusion in the hippocampus and may have selective hippocampal vulnerability to seizure-induced hyperexcitability. Patients with hyperintense signal in the cortical gray matter had episodes of possible hypoperfusion or hypoxia. | 18,723,376 |
Population data for 15 autosomal STRs loci and 12 Y chromosome STRs loci in a population sample from the Sardinia island (Italy). | One hundred twenty-five unrelated individuals (69 females and 56 males) from Sassari (Northern Sardinia) and Orgosolo (Central Sardinia) were typed for 15 STRs loci. The 56 males were typed for 12 Y chromosome STRs loci too. Frequency distribution is described. | 18,723,383 |
Human herpesvirus 8 DNA quantification in matched plasma and PBMCs samples of patients with HHV8-related lymphoproliferative diseases. | The quantitative evaluation of human herpesvirus 8 (HHV8) DNA is not well described in the clinical management of HHV8-related lymphoproliferative diseases. To evaluate and to compare HHV8 viral load in different blood compartments from patients with multicentric Castleman's disease (MCD), primary effusion lymphoma (PEL) and HHV8-associated solid lymphoma (SLY) and to establish which clinical sample would be preferable for HHV8 DNA testing. We assessed HHV8 DNA in plasma and peripheral blood mononuclear cells (PBMCs) paired samples from 7 PEL, 8 MCD, 2 SLY HIV+ patients at the diagnosis and during the course of the illness by using a real time PCR assay. HHV8 viremia was always detectable at diagnosis. HHV8 DNA levels were correlated in matched pairs of samples at diagnosis and during follow-up (Spearman correlation coefficient: r=0.83, p<0.001 and r=0.73, p<0.001, respectively). The performance characteristics of the PCR assay with both materials did not show disparity by the analysis of the receiver operating characteristic (ROC) curve (X(1)(2)=0.50; p=0.48). Plasma or PBMCs are both adequate samples for HHV8 DNA quantification and Real time PCR provides a reliable method to estimate viral replication in patients with HHV8-related lymphoproliferations, where HHV8 viral load is a consistent feature. | 18,723,390 |
Reliability of transcranial magnetic stimulation for mapping swallowing musculature in the human motor cortex. | Although transcranial magnetic stimulation (TMS) has been widely used to study motor cortex organization and excitability, the reliability of this technique has not been thoroughly investigated. Furthermore, previous reports of TMS reliability have been restricted to upper limb musculature. We sought to determine the test-retest reliability for TMS mapping of motor representations for swallowing musculature. Twenty healthy volunteers were tested twice over two weeks using TMS to determine motor threshold, map area, map volume, maximal MEP site location and maximal MEP site size for the suprahyoid complex and pharyngeal musculature. Good test-retest reliability was found in both swallowing muscle sites for the following test parameters: motor map area, maximal MEP site location: lateral coordinate, maximal MEP site size and motor threshold (ICC=0.76-0.98). Moderate reliability was observed for motor map volume and maximal MEP site location: anterior-posterior coordinate (ICC=0.68-0.74). TMS assessments of motor representation size, location and excitability appear to be highly reproducible, although the reliability of these measures may vary according to the specific muscle under investigation. These works provide much needed psychometric data to validate the use of TMS to assess the cortical representation of swallowing musculature. | 18,723,391 |
Identifying the target mRNAs of microRNAs in colorectal cancer. | MicroRNAs (miRNAs) play an important role in gene regulatory networks by inhibiting the expression of target mRNAs. There is a growing interest in identifying the relationship between miRNAs and their target mRNAs. Various experimental studies have been carried out to discover miRNAs involved in cancer and to identify their target genes. At the same time, a large volume of miRNA and mRNA expression profiles have become available owing to the development of high-throughput measurement technologies. So, there is now a pressing need to develop a computational method by which we can identify the target mRNAs of given miRNAs from such massive expression data sets. In this respect, we propose an effective linear model based identification method to unravel the relationship between miRNAs and their target mRNAs in colorectal cancer by using microarray expression profiles and sequence data. | 18,723,399 |
Results of the Cord Blood Transplantation Study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies. | Outcomes of unrelated donor cord blood transplantation in 191 hematologic malignancy children (median age, 7.7 years; median weight, 25.9 kg) enrolled between 1999 and 2003 were studied (median follow-up, 27.4 months) in a prospective phase 2 multicenter trial. Human leukocyte antigen (HLA) matching at enrollment was 6/6 (n = 17), 5/6 (n = 58), 4/6 (n = 111), or 3/6 (n = 5) by low-resolution HLA-A, -B, and high-resolution (HR) DRB1. Retrospectively, 179 pairs were HLA typed by HR. The median precryopreservation total nucleated cell (TNC) dose was 5.1 x 10(7) TNC/kg (range, 1.5-23.7) with 3.9 x 10(7) TNC/kg (range, 0.8-22.8) infused. The median time to engraftment (absolute neutrophil count > 500/mm(3) and platelets 50 000/muL) was 27 and 174 days. The cumulative incidence of neutrophil engraftment by day 42 was 79.9% (95% confidence interval [CI], 75.1%-85.2%); acute grades III/IV GVHD by day 100 was 19.5% (95% CI, 13.9%-25.5%); and chronic GVHD at 2 years was 20.8% (95% CI, 14.8%-27.7%). HR matching decreased the probability of severe acute GVHD. The cumulative incidence of relapse at 2 years was 19.9% (95% CI, 14.8%-25.7%). The probabilities of 6-month and 2-year survivals were 67.4% and 49.5%. Unrelated donor cord blood transplantation from partially HLA-mismatched units can cure many children with leukemias. The study was registered at www.clinicaltrials.gov as #NCT00000603. | 18,723,429 |
Isoniazid or moxifloxacin in rifapentine-based regimens for experimental tuberculosis? | Recent studies have demonstrated that combined substitutions of rifapentine for rifampin and moxifloxacin for isoniazid in the standard, daily, short-course regimen of rifampin, isoniazid, and pyrazinamide produces stable cure in 12 weeks or less. This study was designed to more precisely evaluate the contribution of moxifloxacin and isoniazid to rifapentine-based regimens. We compared bactericidal activity and treatment-shortening potential between regimens consisting of isoniazid or moxifloxacin plus rifapentine and pyrazinamide administered either thrice-weekly or daily. Using a mouse model of tuberculosis, we assessed bactericidal activity by performing quantitative cultures of lung homogenates over the first 12 weeks of treatment. Relapse rates were assessed after completing 8, 10, and 12 weeks of treatment to determine the duration of treatment necessary for stable cure. After 4 weeks of treatment, daily and thrice-weekly therapy with rifapentine, moxifloxacin, and pyrazinamide was significantly more active than treatment with rifapentine, isoniazid, and pyrazinamide. By 8 weeks of treatment, all mice receiving the moxifloxacin-containing regimens were lung culture negative, whereas those mice receiving the isoniazid-containing regimens continued to be lung culture positive. However, the duration of treatment necessary to achieve stable cure was 10 weeks for daily regimens and 12 weeks for thrice-weekly regimens, regardless of whether isoniazid or moxifloxacin was used. All mice receiving standard daily therapy with rifampin, isoniazid, and pyrazinamide relapsed after 12 weeks of treatment. These results suggest that regimens consisting of isoniazid or moxifloxacin plus rifapentine and pyrazinamide may dramatically shorten the duration of treatment needed to cure human tuberculosis. | 18,723,432 |
Vascular endothelial growth factor and semaphorin induce neuropilin-1 endocytosis via separate pathways. | The neuropilin (Nrp)1 receptor is essential for both nervous and vascular system development. Nrp1 is unusually versatile, because it transmits both chemoattractive and repulsive signals in response to vascular endothelial growth factor (VEGF)-A and class 3 semaphorins, respectively. Both Nrp1 and VEGF receptor 2 undergo ligand-dependent endocytosis. We sought to establish the endocytic pathway of Nrp1 and to determine whether uptake is required for its signaling. Whereas Nrp1 underwent clathrin-dependent endocytosis in response to VEGFA(165) treatment, semaphorin 3C (sema3C) induced lipid raft-dependent endocytosis. The myosin VI PDZ (postsynaptic density 95, Disk large, Zona occludens-1) adaptor protein synectin was essential for Nrp1 trafficking. Sema3C failed to inhibit migration of synectin(-/-) endothelial cells, mirroring the lower migratory response of these cells to VEGFA(165). These results show that the endocytic pathway of Nrp1 is determined by its ligand and that the trafficking of Nrp1 is essential for its signaling. | 18,723,443 |
High-content imaging characterization of cell cycle therapeutics through in vitro and in vivo subpopulation analysis. | Although the cycling of eukaryotic cells has long been a primary focus for cancer therapeutics, recent advances in imaging and data analysis allow even further definition of cellular events as they occur in individual cells and cellular subpopulations in response to treatment. High-content imaging (HCI) has been an effective tool to elucidate cellular responses to a variety of agents; however, these data were most frequently observed as averages of the entire captured population, unnecessarily decreasing the resolution of each assay. Here, we dissect the eukaryotic cell cycle into individual cellular subpopulations using HCI in conjunction with unsupervised K-means clustering. We generate distinct phenotypic fingerprints for each major cell cycle and mitotic compartment and use those fingerprints to screen a library of 310 commercially available chemotherapeutic agents. We determine that the cell cycle arrest phenotypes caused by these agents are similar to, although distinct from, those found in untreated cells and that these distinctions frequently suggest the mechanism of action. We then show via subpopulation analysis that these arrest phenotypes are similar in both mouse models and in culture. HCI analysis of cell cycle using data obtained from individual cells under a broad range of research conditions and grouped into cellular subpopulations represents a powerful method to discern both cellular events and treatment effects. In particular, this technique allows for a more accurate means of assessing compound selectivity and leads to more meaningful comparisons between so-called targeted therapeutics. | 18,723,491 |
Tumor-associated CD75s- and iso-CD75s-gangliosides are potential targets for adjuvant therapy in pancreatic cancer. | Pancreatic adenocarcinoma confers one of the highest mortality rates in malignant human tumors with very poor prognosis. Because as yet no treatments are available that produce a substantial survival benefit for this fatal neoplasia, new therapeutic concepts are urgently required to support cancer standard treatment. In search of tumor-associated gangliosides with therapeutic background, we probed a random collection of cancerous and adjacent normal postoperative tissue samples from 38 patients for the expression of CD75s- and iso-CD75s-gangliosides. We exhaustively analyzed the expression of CD75s-1-ganglioside (IV(6)Neu5Ac-nLc4Cer) and structurally closely related iso-CD75s-1-ganglioside (IV(3)Neu5Ac-nLc4Cer) by means of immunohistology of cryosections and semiquantitative TLC of tissue lipid extracts combined with mass spectrometry. CD75s-1- and iso-CD75s-1-ganglioside showed an elevated expression in 42% and 66% of the tumors, respectively, indicating a significant association with neoplastic transformation (P = 0.001). Thus, increased expression of CD75s-1- and iso-CD75s-1-gangliosides renders these cell surface molecules promising candidates for oncologic applications. Further statistical analysis revealed a significant enhancement of CD75s-1-ganglioside in the group of less differentiated tumors (grade >2) suggesting this ganglioside as a potential marker for poor differentiation. The CD75s-specific antitumor drug rViscumin, which represents the recombinant counterpart of the ribosome-inactivating lectin viscumin, has successfully passed clinical phase I trials and provides an opportunity for treating pancreatic cancer. Consequently, if an enhanced expression is existent in malignant tissues, we propose the targeting of CD75s-gangliosides with rViscumin as a novel potential strategy in adjuvant treatment of pancreatic malignancies. | 18,723,492 |
Chondrocyte aggregation in suspension culture is GFOGER-GPP- and beta1 integrin-dependent. | Isolated chondrocytes form aggregates in suspension culture that maintain chondrocyte phenotype in a physiological pericellular environment. The molecular mechanisms involved in chondrocyte aggregation have not been previously identified. Using this novel suspension culture system, we performed mRNA and protein expression analysis along with immunohistochemistry for potential cell adhesion molecules and extracellular matrix integrin ligands. Inhibition of aggregation assays were performed using specific blocking agents. We found that: (i) direct cell-cell interactions were not involved in chondrocyte aggregation, (ii) chondrocytes in aggregates were surrounded by a matrix rich in collagen II and cartilage oligomeric protein (COMP), (iii) aggregation depends on a beta1-integrin, which binds a triple helical GFOGER sequence found in collagens, (iv) integrin alpha10-subunit is the most highly expressed alpha-subunit among those tested, including alpha5, in aggregating chondrocytes. Taken together, this body of evidence suggests that the main molecular interaction involved in aggregation of phenotypically stable chondrocytes is the alpha10beta1-collagen II interaction. | 18,723,503 |
Protein kinase G-dependent cardioprotective mechanism of phosphodiesterase-5 inhibition involves phosphorylation of ERK and GSK3beta. | Sildenafil, a potent inhibitor of phosphodiesterase-5 (PDE-5) induces powerful protection against myocardial ischemia-reperfusion injury. PDE-5 inhibition increases cGMP levels that activate cGMP-dependent protein kinase (PKG). However, the cause and effect relationship of PKG in sildenafil-induced cardioprotection and the downstream targets of PKG remain unclear. Adult ventricular myocytes were treated with sildenafil and subjected to simulated ischemia and reoxygenation. Sildenafil treatment significantly decreased cardiomyocyte necrosis and apoptosis. The PKG inhibitors, KT5823, guanosine 3',5'-cyclic monophosphorothioate, 8-(4-chloro-phenylthio) (R(p)-8-pCPT-cGMPs), or DT-2 blocked the anti-necrotic and anti-apoptotic effect of sildenafil. Selective knockdown of PKG in cardiomyocytes with adenoviral vector containing short hairpin RNA of PKG also abolished sildenafil-induced protection. Furthermore, intra-coronary infusion of sildenafil in Langendorff-isolated mouse hearts prior to ischemia-reperfusion significantly reduced myocardial infarct size after 20 min ischemia and 30 min reperfusion, which was abrogated by KT5823. Sildenafil significantly increased PKG activity in intact hearts and cardiomyocytes. Sildenafil also enhanced the Bcl-2/Bax ratio, phosphorylation of Akt, ERK1/2, and glycogen synthase kinase 3beta. All these changes (except Akt phosphorylation) were significantly blocked by KT5823 and short hairpin RNA of PKG. These studies provide the first evidence for an essential role of PKG in sildenafil-induced cardioprotection. Moreover, our results demonstrate that sildenafil activates a PKG-dependent novel signaling cascade that involves activation of ERK and inhibition of glycogen synthase kinase 3beta leading to cytoprotection. | 18,723,505 |
Three-dimensional reconstruction of human cystic fibrosis transmembrane conductance regulator chloride channel revealed an ellipsoidal structure with orifices beneath the putative transmembrane domain. | The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is a membrane-integral protein that belongs to an ATP-binding cassette superfamily. Mutations in the CFTR gene cause cystic fibrosis in which salt, water, and protein transports are defective in various tissues. Here we expressed wild-type human CFTR as a FLAG-fused protein in HEK293 cells heterologously and purified it in three steps: anti-FLAG and wheat germ agglutinin affinity chromatographies and size exclusion chromatography. The stoichiometry of the protein was analyzed using various biochemical approaches, including chemical cross-linking, blue-native PAGE, size exclusion chromatography, and electron microscopy (EM) observation of antibody-decorated CFTR. All these data support a dimeric assembly of CFTR. Using 5,039 automatically selected particles from negatively stained EM images, the three-dimensional structure of CFTR was reconstructed at 2-nm resolution assuming a 2-fold symmetry. CFTR, presumably in a closed state, was shown to be an ellipsoidal particle with dimensions of 120 x 106 x 162 A. It comprises a small dome-shaped extracellular and membrane-spanning domain and a large cytoplasmic domain with orifices beneath the putative transmembrane domain. EM observation of CFTR.anti-regulatory domain antibody complex confirmed that two regulatory domains are located around the bottom end of the larger oval cytoplasmic domain. | 18,723,516 |
The effects of short-term antioxidant supplementation on oxidative stress and flight performance in adult budgerigars Melopsittacus undulatus. | Antioxidants are known to play an important role in quenching reactive oxygen species (ROS), thus ameliorating oxidative stress. Since increased metabolism associated with exercise can increase oxidative stress, dietary antioxidants may be a limiting factor in determining aspects of physical performance. Here we tested whether oxidative stress associated with flight exercise of captive adult budgerigars, Melopsittacus undulatus differed after they received a diet containing either enhanced (EQ) or reduced levels (RQ) of a nutritional supplement (Nutrivit) rich in antioxidants for 4 weeks. We also assessed differences in take-off escape time, a potential fitness-determining physiological capability. Oxidative stress was measured in two ways: comet assay to measure DNA damage; and analysis of malondialdehyde (MDA), a by-product of lipid peroxidation. Flight exercise appeared to increase oxidative stress. Moreover, birds had a higher percentage of intact DNA (fewer alkali labile sites) in one comet measure and lower levels of MDA after an EQ diet than after an RQ diet. We found no difference in flight performance between the two diets. Our results suggested that birds exerted maximum effort in escape flights, regardless of diet. However, this was at a cost of increased oxidative stress post-flight when on a reduced quality diet, but not when on an enhanced, antioxidant-rich diet. We suggest that dietary antioxidants may prove important in reducing exercise-related costs through multiple physiological pathways. Further work is necessary to fully understand the effects of antioxidants and oxidative stress on exercise performance in the longer term. | 18,723,545 |
Sustained changes in lipid profile and macrophage migration inhibitory factor levels after anti-tumour necrosis factor therapy in rheumatoid arthritis. | Macrophage migration inhibitory factor (MIF) has recently emerged as an important cytokine possibly linking rheumatoid arthritis (RA) and atherogenesis. Because atherogenesis is accelerated in RA this study was conducted to investigate whether anti-tumour necrosis factor (TNF) therapy could lead to sustained downregulation of systemic MIF levels and improvement in lipid profiles. Fifty RA patients with active disease (disease activity score in 28 joints (DAS28) >or=3.2), who started adalimumab therapy at 40 mg every other week, were included. At baseline, weeks 16 and 52 serum levels of MIF and lipids were assessed. In addition, the DAS28 and serum C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) were determined. After 16 weeks of adalimumab therapy, both DAS28 and MIF levels were significantly decreased (p<0.001 and p = 0.020, respectively). This was sustained up to week 52 (p<0.001 and p = 0.012, respectively). CRP levels and ESR were significantly reduced after 16 and 52 weeks of adalimumab therapy (p<0.001). High-density lipoprotein cholesterol levels increased at week 16 (p<0.001), but returned to baseline at week 52. Apolipoprotein (apo) A-I levels increased at week 16 (p<0.001) and remained stable (p = 0.005). This resulted in an improved apo B/A-I ratio. The results underline the sustained downregulation of MIF as a potential new mechanism by which anti-TNF therapy might reduce vascular inflammation, and as such perhaps cardiovascular morbidity in RA patients. This hypothesis is supported by an improved apo B/A-I ratio as well as reduced CRP levels in these patients. | 18,723,565 |
Clerocidin selectively modifies the gyrase-DNA gate to induce irreversible and reversible DNA damage. | Clerocidin (CL), a microbial diterpenoid, reacts with DNA via its epoxide group and stimulates DNA cleavage by type II DNA topoisomerases. The molecular basis of CL action is poorly understood. We establish by genetic means that CL targets DNA gyrase in the gram-positive bacterium Streptococcus pneumoniae, and promotes gyrase-dependent single- and double-stranded DNA cleavage in vitro. CL-stimulated DNA breakage exhibited a strong preference for guanine preceding the scission site (-1 position). Mutagenesis of -1 guanines to A, C or T abrogated CL cleavage at a strong pBR322 site. Surprisingly, for double-strand breaks, scission on one strand consistently involved a modified (piperidine-labile) guanine and was not reversed by heat, salt or EDTA, whereas complementary strand scission occurred at a piperidine-stable -1 nt and was reversed by EDTA. CL did not induce cleavage by a mutant gyrase (GyrA G79A) identified here in CL-resistant pneumococci. Indeed, mutations at G79 and at the neighbouring S81 residue in the GyrA breakage-reunion domain discriminated poisoning by CL from that of antibacterial quinolones. The results suggest a novel mechanism of enzyme inhibition in which the -1 nt at the gyrase-DNA gate exhibit different CL reactivities to produce both irreversible and reversible DNA damage. | 18,723,572 |
Negative vascular remodelling after implantation of bioabsorbable magnesium alloy stents in porcine coronary arteries: a randomised comparison with bare-metal and sirolimus-eluting stents. | We sought to assess vascular remodelling and neointima formation after implantation of bioabsorbable magnesium alloy stents (AMS). Randomised experimental study. AMS (n = 11), sirolimus-eluting stents (Cypher; n = 11) and bare-metal stents (BMS; n = 9) were randomly implanted in 31 porcine coronary arteries (n = 11 pigs). Neointima formation was measured by histomorphometry at 90 days. Vascular remodelling defined as change in external elastic membrane area from index intervention to follow-up was assessed by serial intravascular ultrasound (IVUS). By histomorphometry, lumen (median (quartiles); AMS: 1.75 mm2 (1.07-3.26), Cypher 2.52 mm2 (2.22-5.01), BMS 4.55 mm2 (3.2-7.44); p = 0.013) and external elastic membrane area (AMS: 5.56 mm2 (4.09-6.95), Cypher 7.95 mm2 (6.45-10.92), BMS 9.08 mm2 (7.85-11.63); p = 0.014) were smallest after AMS implantation. By IVUS, external elastic membrane area at follow-up was smallest (AMS: 7.5 (2.8) mm2, Cypher 9.1 (2.7) mm2, BMS 9.9 (3.1) mm2; p = 0.33) and change in external elastic membrane area from index intervention to follow-up (remodelling; AMS: -1.0 (3.1) mm2, Cypher 1.0 (0.8) mm2, BMS 0.9 (1.2) mm2; p = 0.30) was greatest in the AMS group. In a dichotomised IVUS assessment of vascular remodelling, six AMS stents were remodelled (negative remodelling: n = 5; positive remodelling: n = 1) at 90-day follow-up (AMS versus Cypher + BMS: p = 0.001). Neointima formation was smallest in the AMS group (p<0.05 for both histomorphometry and IVUS). Coronary implantation of absorbable magnesium stents, compared to two non-absorbable stents, was associated with the smallest lumen area at three-month follow-up because of negative vascular remodelling. | 18,723,586 |
The social behaviours of bacterial pathogens. | The term quorum sensing (QS) is used to describe communication between bacterial cells, whereby a coordinated population response is controlled by diffusible signal molecules produced by individuals. Studies on QS-mediated signalling processes in bacteria have revealed the existence of intricate regulatory networks to enable bacterial populations to fine tune their responses to environmental changes and increase their chances of survival, using complex signalling pathways. A population of bacteria invading a host may benefit from the coordinated release of virulence determinants and in vitro studies have shown that QS regulates virulence factor production in many species of bacteria. However, the role of QS in vivo is less well understood, but has been demonstrated to be important in several pathogenic organisms. There is a growing interest in blocking bacterial cell-cell communication as a means to control infections. This review discusses QS from a pathogenic perspective and discusses the potential of QS as an anti-pathogenic target. | 18,723,587 |
Updates on improvement of human athletic performance: focus on world records in athletics. | Progression of world records (WRs) in athletics is a reliable mean to assess the potentiality of the human body, which also reflects how society has evolved over time and will continue to evolve. We conducted a quantitative analysis of WRs in measurable Olympic events from nine representative disciplines (100, 400, 1500, 10,000 m, marathon, long jump, high jump, shot put and javelin throw) in order to identify progression and trends. Data were gathered for the years 1900-2007 from the database of the International Olympic Committee. Overall, the relative improvement of athletic performance was higher in women than in men, being nearly doubled across the different specialities. The biggest increases were observed for javelin throw and shot put, in both men and women, respectively. Conversely, the improvement in race time was directly related to the race distance. We also observed a consistent significant linear model of WRs progression in time, although the improvement has substantially stopped or reached a plateau in several specialities. The observed trend might be explained by a variety of factors, including social and environmental changes, natural selection, advances in training and sport physiology, ergogenic aids and, possibly, doping. These results are discussed in a multifaceted approach, taking into account several biological, environmental and technological issues that might explain the trends observed. | 18,723,588 |
The origins of 168, W23, and other Bacillus subtilis legacy strains. | Bacillus subtilis is both a model organism for basic research and an industrial workhorse, yet there are major gaps in our understanding of the genomic heritage and provenance of many widely used strains. We analyzed 17 legacy strains dating to the early years of B. subtilis genetics. For three--NCIB 3610T, PY79, and SMY--we performed comparative genome sequencing. For the remainder, we used conventional sequencing to sample genomic regions expected to show sequence heterogeneity. Sequence comparisons showed that 168, its siblings (122, 160, and 166), and the type strains NCIB 3610 and ATCC 6051 are highly similar and are likely descendants of the original Marburg strain, although the 168 lineage shows genetic evidence of early domestication. Strains 23, W23, and W23SR are identical in sequence to each other but only 94.6% identical to the Marburg group in the sequenced regions. Strain 23, the probable W23 parent, likely arose from a contaminant in the mutagenesis experiments that produced 168. The remaining strains are all genomic hybrids, showing one or more "W23 islands" in a 168 genomic backbone. Each traces its origin to transformations of 168 derivatives with DNA from 23 or W23. The common prototrophic lab strain PY79 possesses substantial W23 islands at its trp and sac loci, along with large deletions that have reduced its genome 4.3%. SMY, reputed to be the parent of 168, is actually a 168-W23 hybrid that likely shares a recent ancestor with PY79. These data provide greater insight into the genomic history of these B. subtilis legacy strains. | 18,723,616 |
Purification and characterization of the bacterial UDP-GlcNAc:undecaprenyl-phosphate GlcNAc-1-phosphate transferase WecA. | To date, the structural and functional characterization of proteins belonging to the polyprenyl-phosphate N-acetylhexosamine-1-phosphate transferase superfamily has been relentlessly held back by problems encountered with their overexpression and purification. In the present work and for the first time, the integral membrane protein WecA that catalyzes the transfer of the GlcNAc-1-phosphate moiety from UDP-GlcNAc onto the carrier lipid undecaprenyl phosphate, yielding undecaprenyl-pyrophosphoryl-GlcNAc, the lipid intermediate involved in the synthesis of various bacterial cell envelope components, was overproduced and purified to near homogeneity in milligram quantities. An enzymatic assay was developed, and the kinetic parameters of WecA as well as the effects of pH, salts, cations, detergents, and temperature on the enzyme activity were determined. A minimal length of 35 carbons was required for the lipid substrate, and tunicamycin was shown to inhibit the enzyme at submicromolar concentrations. | 18,723,618 |
Characterization of spores of Bacillus subtilis that lack most coat layers. | Spores of Bacillus subtilis have a thick outer layer of relatively insoluble protein called the coat, which protects spores against a number of treatments and may also play roles in spore germination. However, elucidation of precise roles of the coat in spore properties has been hampered by the inability to prepare spores lacking all or most coat material. In this work, we show that spores of a strain with mutations in both the cotE and gerE genes, which encode proteins involved in coat assembly and expression of genes encoding coat proteins, respectively, lack most extractable coat protein as seen by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, as well as the great majority of the coat as seen by atomic force microscopy. However, the cotE gerE spores did retain a thin layer of insoluble coat material that was most easily seen by microscopy following digestion of these spores with lysozyme. These severely coat-deficient spores germinated relatively normally with nutrients and even better with dodecylamine but not with a 1:1 chelate of Ca(2+) and dipicolinic acid. These spores were also quite resistant to wet heat, to mechanical disruption, and to treatment with detergents at an elevated temperature and pH but were exquisitely sensitive to killing by sodium hypochlorite. These results provide new insight into the role of the coat layer in spore properties. | 18,723,620 |
Stygiolobus rod-shaped virus and the interplay of crenarchaeal rudiviruses with the CRISPR antiviral system. | A newly characterized archaeal rudivirus Stygiolobus rod-shaped virus (SRV), which infects a hyperthermophilic Stygiolobus species, was isolated from a hot spring in the Azores, Portugal. Its virions are rod-shaped, 702 (+/- 50) by 22 (+/- 3) nm in size, and nonenveloped and carry three tail fibers at each terminus. The linear double-stranded DNA genome contains 28,096 bp and an inverted terminal repeat of 1,030 bp. The SRV shows morphological and genomic similarities to the other characterized rudiviruses Sulfolobus rod-shaped virus 1 (SIRV1), SIRV2, and Acidianus rod-shaped virus 1, isolated from hot acidic springs of Iceland and Italy. The single major rudiviral structural protein is shown to generate long tubular structures in vitro of similar dimensions to those of the virion, and we estimate that the virion constitutes a single, superhelical, double-stranded DNA embedded into such a protein structure. Three additional minor conserved structural proteins are also identified. Ubiquitous rudiviral proteins with assigned functions include glycosyl transferases and a S-adenosylmethionine-dependent methyltransferase, as well as a Holliday junction resolvase, a transcriptionally coupled helicase and nuclease implicated in DNA replication. Analysis of matches between known crenarchaeal chromosomal CRISPR spacer sequences, implicated in a viral defense system, and rudiviral genomes revealed that about 10% of the 3,042 unique acidothermophile spacers yield significant matches to rudiviral genomes, with a bias to highly conserved protein genes, consistent with the widespread presence of rudiviruses in hot acidophilic environments. We propose that the 12-bp indels which are commonly found in conserved rudiviral protein genes may be generated as a reaction to the presence of the host CRISPR defense system. | 18,723,627 |
Identification of chemosensory sensilla mediating antennular flicking behavior in Panulirus argus, the Caribbean spiny lobster. | Crustaceans sample odorants by a rapid series of flicks of the two flagella composing the distal segments of each of the paired antennules. The lateral flagella contain aesthetasc sensilla that house unimodal chemosensory neurons. Nine types of nonaesthetasc setae with putative chemosensory and mechanosensory functions are distributed on the lateral and medial flagella. Sensory neurons in aesthetascs and nonaesthetasc sensilla terminate in separate regions of the brain, the olfactory lobe, and the lateral antennular neuropil, resulting in two odorant-processing pathways. Distilled water ablation of flagella and excision of specific setae were used to identify chemosensory sensilla mediating antennular flick behavior in Panulirus argus. The flick rates of sham-ablated and ablated or excised lobsters toward squid extract were compared. Complete attenuation of flick response to squid extract occurred as a result of (1) distilled water ablation of lateral flagella, (2) excision of aesthetascs and asymmetric sensilla, and (3) excision of aesthetascs. Distilled water ablation of medial flagella resulted in a mean flick rate 52% of that observed for sham-ablated lobsters toward squid extract. Flicking was unaffected by excision of asymmetric, guard, or companion sensilla. We propose that odorant mediation of flicking behavior requires both the aesthetasc and nonaesthetasc pathways. | 18,723,634 |
Rhythms of locomotion expressed by Limulus polyphemus, the American horseshoe crab: I. Synchronization by artificial tides. | Limulus polyphemus, the American horseshoe crab, has an endogenous clock that drives circatidal rhythms of locomotor activity. In this study, we examined the ability of artificial tides to entrain the locomotor rhythms of Limulus in the laboratory. In experiments one and two, the activity of 16 individuals of L. polyphemus was monitored with activity boxes and "running wheels." When the crabs were exposed to artificial tides created by changes in water depth, circatidal rhythms were observed in animals exposed to 12.4-h "tidal" cycles of either water depth changes (8 of 8 animals) or inundation (7 of 8 animals). In experiment three, an additional 8 animals were exposed to water depth changes under cyclic conditions of light and dark and then monitored for 10 days with no imposed artificial tides. Most animals (5) clearly synchronized their activity to the imposed artificial tidal cycles, and 3 of these animals showed clear evidence of entrainment after the artificial tides were terminated. Overall, these results demonstrate that the endogenous tidal clock that influences locomotion in Limulus can be entrained by imposed artificial tides. In the laboratory, these tidal cues override the influence of light/dark cycles. In their natural habitat, where both tidal and photoperiod inputs are typically always present, their activity rhythms are likely to be much more complex. | 18,723,635 |
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