title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Kinematic assessment of paediatric forefoot varus. | Forefoot varus is a static deformity not easy to assess clinically. If left uncorrected, it is thought to affect both the posture of the patient and the kinematics of their lower limbs, and even the spine. Three-dimensional gait assessment could help to confirm forefoot varus diagnosis and provide objective evidence of the functional adaptive mechanisms postulated in the literature. The recently available Oxford Foot Model was used, simultaneously with a conventional lower limb model, to compare the kinematics of 10 forefoot varus children (aged 8-13) and 11 healthy controls (aged 7-13) during gait. Data acquisition was performed using a six-camera motion capture system, with a total of 27 reflective markers. A patient-by-patient comparison with the controls suggested several compensation patterns, although statistically significant differences were found only for the mean values of hip adduction/abduction during load response and midstance and hip flexion/extension during pre-swing. A multivariate statistical technique was used to determine which of the measured variables better separated both groups. The best discriminant model presented here includes hip adduction/abduction during load response, hindfoot/tibia inversion/eversion during pre-swing, hindfoot/tibia dorsiflexion/plantar flexion during load response and arch height during midstance, providing a rate of correct classification of 81%. The results could not fully confirm the kinematic relationships suggested in the literature. The small degree of forefoot varus deformity present in the patient group could have prevented other variables from becoming discriminant. A larger patient sample would help determine the possible different compensatory patterns to different degrees of forefoot varus. | 18,829,322 |
Alpha-tocopherol protects against oxidative damage to lipids of the rod outer segments of the equine retina. | Oxidative stress is a possible risk factor for eye diseases. Lipid peroxidation is one of the major events induced by oxidative stress and is particularly active in polyunsaturated fatty acid (PUFA)-rich biomembranes. This work evaluated endogenous lipid antioxidants, in vitro non-enzymatic lipid peroxidation of rod outer segment membranes (ROS), the fatty acid composition during oxidative damage of total lipids from equine retina and ROS, and the protective action of alpha-tocopherol (alpha-Toc). The major lipid soluble antioxidant was alpha-Toc followed by retinoids and carotenoids. The retina contained a high percentage of PUFAs, mainly docosahexaenoic acid (22:6n-3) and arachidonic acid (20:4n-6). Lipid peroxidation of the equine ROS, induced by Fe(2+)-ascorbate, was monitored using chemiluminescence (CL) with or without pre-treatment with alpha-Toc. With alpha-Toc pre-treatment, CL values were significantly decreased. The most abundant fatty acid was 22:6n-3. After 3h incubation, 95% of total PUFAs were destroyed by peroxidation, whereas in alpha-Toc pre-treated ROS the percentage was significantly decreased. The results show that the retina has an endogenous lipid soluble antioxidant system. ROS were highly sensitive to oxidative damage, since their fatty acid composition was markedly modified during the lipid peroxidation process. The protective role of alpha-Toc as an antioxidant was evident and it could be used in the treatment of equine ocular diseases in which free radicals are involved. | 18,829,353 |
Salmonella: the pelvic masquerader. | Salmonella sp is a significant cause of morbidity and mortality. Although commonly infecting the gastrointestinal system, other presentations are not unheard of. Salmonella is an unlikely and an unusual cause of genital tract infection. We describe a woman with suspected pelvic inflammatory disease eventually confirmed as Salmonella O C2 infection. | 18,829,361 |
Model analysis of local oxygen delivery with liposome-encapsulated hemoglobin. | Liposome-encapsulated hemoglobins (LHs) are comparable to red blood cells (RBCs) in terms of oxygen (O(2))-carrying capacity. The smaller particle size of LHs than of platelets allows their homogeneous dispersion in circulating plasma. In this study, we evaluated the effect of LH transfusion on arterial O(2) delivery through vascular trees by simulation. A mathematical model was established on the basis of the coronary arterial anatomy, the conservation of flow and RBC flux, and Poiseuille's law. The Fåhraeus-Lindqvist, Fåhraeus, and phase separation effects were considered in the model. By assuming steady perfusion, the arterial flow and O(2) delivery were calculated for five model trees undergoing the isovolumic replacement of RBCs (0.3 mg hemoglobin (Hb)/mL) with LHs (0.2 mg Hb/mL) or a plasma volume expander (PVE). The RBC-LH exchange increased both the total flow and the total O(2) flux but had almost no effect on the relative distribution of O(2) flux. In contrast, the RBC-PVE exchange decreased the total O(2) flux and increased the proportion of regions receiving a relatively low O(2) supply. Thus, LH transfusion may compensate for an enhanced bias in RBC-associated O(2) flux under hemodilution and is expected to be beneficial for both total and local O(2) delivery. | 18,829,372 |
Glucosidase-beta variations and Lewy body disorders. | It has been proposed that there is an increased frequency of glucosidase-beta mutations in Lewy body disorders. Our comprehensive DNA sequencing approach found a small number of glucosidase-beta mutations in 101 neuropathologically defined Lewy body disease cases (3%) compared to 99 healthy post-mortem controls (1%); odds ratio 3.0 (95% CI: 0.3-29, p=0.3). All three affected carriers were classified as diffuse Lewy body disease (n=3/50; 6%). Our study suggests glucosidase-beta variants have a limited role in susceptibility to Lewy body disease in North America. | 18,829,375 |
Mixed respiratory virus infections. | Mixed respiratory viral infections are double negative common and evidence that they are associated with severe disease is supported by some groups. This controversial observation can be explained by the lack of sensitivity of the assessed methods used for viral identification and by the small number of patients included in the randomized cohorts studied. Most studies showed that respiratory syncytial virus (RSV) is identified in about 70% of hospitalized infants with bronchiolitis during seasonal winter epidemics, followed by human metapneumovirus (hMPV, about 3-19%) or rhinoviruses (about 20%). Other respiratory viruses have also been reported, indicating significant causes of bronchiolitis and hospitalization during seasonal epidemics. The presence of more than one pathogen, and moreover, the association of RSV with rhinoviruses and also RSV with hMPV, may influence the natural course of bronchiolitis. A better understanding of these various interactions would help future decision-making, such as the extent to which searches for co-pathogens should be conducted in severe bronchiolitis patients already infected by RSV. | 18,829,380 |
Immune-mediated neuropathies in myeloma patients treated with bortezomib. | Bortezomib is a new chemotherapeutic drug available for the treatment of lymphoid disorders, including multiple myeloma. Although its primary mechanism of action is proteasome inhibition, other mechanisms can contribute to the therapeutic effects, including modulation of inflammatory cytokines and immune response. One of the main toxic effects of bortezomib is peripheral neuropathy, usually occurring in the form of a painful, sensory axonal neuropathy. The mechanisms of peripheral damage, however, are still unclear. We here report a series of patients treated with bortezomib, who developed a peripheral damage possibly related to immuno-mediated, rather than toxic, mechanisms. Five patients who developed a peripheral neuropathy with severe motor involvement under bortezomib treatment underwent CSF, electrophysiological, and spinal cord MRI examinations. Peripheral damage was characterized by: demyelinating or mixed axonal-demyelinating neuropathy, with prominent motor involvement; albumin-cytological dissociation; lumbar root enhancement on MRI in 2/5 patients; favourable outcome in 4/5 patients after immune treatments, either steroids (2 patients) or IVIg (2 patients). In some instances, the peripheral damage associated with bortezomib may recognize immuno-mediated mechanisms. This form of bortezomib-associated neuropathy needs to be recognized as treatable condition, as it may respond to immune therapies. Unexplained worsening of neurological dysfunction despite bortezomib discontinuation, with prominent motor involvement and CSF signs of inflammation, may be the clues to this complication. | 18,829,381 |
Targeting of albumin-embedded paclitaxel nanoparticles to tumors. | We have used tumor-homing peptides to target abraxane, a clinically approved paclitaxel-albumin nanoparticle, to tumors in mice. The targeting was accomplished with two peptides, CREKA and LyP-1 (CGNKRTRGC). Fluorescein (FAM)-labeled CREKA-abraxane, when injected intravenously into mice bearing MDA-MB-435 human cancer xenografts, accumulated in tumor blood vessels, forming aggregates that contained red blood cells and fibrin. FAM-LyP-1-abraxane co-localized with extravascular islands expressing its receptor, p32. Self-assembled mixed micelles carrying the homing peptide and the label on different subunits accumulated in the same areas of tumors as LyP-1-abraxane, showing that Lyp-1 can deliver intact nanoparticles into extravascular sites. Untargeted, FAM-abraxane was detected in the form of a faint meshwork in tumor interstitium. LyP-1-abraxane produced a statistically highly significant inhibition of tumor growth compared with untargeted abraxane. These results show that nanoparticles can be effectively targeted into extravascular tumor tissue and that targeting can enhance the activity of a therapeutic nanoparticle. | 18,829,396 |
Electrical characterization of hydroxyapatite-based bioceramics. | This paper studies the AC conductivity and permittivity of hydroxyapatite (HA)-based ceramics from 0.1 Hz-1 MHz at temperatures from room temperature to 1000 degrees C. HA-based ceramics were prepared either as dense ceramics or in porous form with interconnected porosity and were sintered in either air or water vapour. Samples were thermally cycled to examine the influence of water desorption on AC conductivity and permittivity. Surface-bound water was thought to contribute to conductivity for both dense and porous materials at temperatures below 200 degrees C. At temperatures below 700 degrees C the permittivity and AC conductivity of HA was also influenced by the degree of dehydration and thermal history. At higher temperatures (700-1000 degrees C), bulk ionic conduction was dominant and activation energies were of the order of approximately 2 eV, indicating that hydroxyl ions are responsible for conductivity. | 18,829,403 |
How academic psychiatry can better prepare students for their future patients. Part I: the failure to recognize depression and risk for suicide in primary care; problem identification, responsibility, and solutions. | The author, after a review of the relevant literature, found that depression and the risk for suicide remain unacceptably underrecognized in primary care (PC). The negative consequences are substantial for patients and their physicians. Suicide prevention in PC begins with the recognition of depression because suicide occurs largely during depression. In this article (Part I), the author suggests causes, responsibilities, and solutions for that failure. He also addresses the role of academic psychiatry's traditional curriculum. The comprehensive, initial diagnostic interview that is typically taught to medical students in psychiatry may decrease recognition in PC care because of the time required to complete it. In Part II, the author offers guidelines to develop a weekly interview course with an instrument targeting abbreviated diagnostic screening for only the most critical psychiatric problems such as depression and the risk for suicide. | 18,829,423 |
The role of the striatum in aversive learning and aversive prediction errors. | Neuroeconomic studies of decision making have emphasized reward learning as critical in the representation of value-driven choice behaviour. However, it is readily apparent that punishment and aversive learning are also significant factors in motivating decisions and actions. In this paper, we review the role of the striatum and amygdala in affective learning and the coding of aversive prediction errors (PEs). We present neuroimaging results showing aversive PE-related signals in the striatum in fear conditioning paradigms with both primary (shock) and secondary (monetary loss) reinforcers. These results and others point to the general role for the striatum in coding PEs across a broad range of learning paradigms and reinforcer types. | 18,829,426 |
The role of social cognition in decision making. | Successful decision making in a social setting depends on our ability to understand the intentions, emotions and beliefs of others. The mirror system allows us to understand other people's motor actions and action intentions. 'Empathy' allows us to understand and share emotions and sensations with others. 'Theory of mind' allows us to understand more abstract concepts such as beliefs or wishes in others. In all these cases, evidence has accumulated that we use the specific neural networks engaged in processing mental states in ourselves to understand the same mental states in others. However, the magnitude of the brain activity in these shared networks is modulated by contextual appraisal of the situation or the other person. An important feature of decision making in a social setting concerns the interaction of reason and emotion. We consider four domains where such interactions occur: our sense of fairness, altruistic punishment, trust and framing effects. In these cases, social motivations and emotions compete with each other, while higher-level control processes modulate the interactions of these low-level biases. | 18,829,429 |
Congenital abnormalities and acute leukemia among children with Down syndrome: a Children's Oncology Group study. | Children with Down syndrome, due to their heightened risk of leukemia and increased prevalence of congenital abnormalities, comprise a valuable population in which to study etiology. A Children's Oncology Group study investigated the causes of childhood leukemia in children with Down syndrome diagnosed at ages 0 to 19 years during the period 1997-2002. Telephone interviews were completed with mothers of 158 cases [n=97 acute lymphoblastic leukemia (ALL) and n=61 acute myeloid leukemia (AML)] and 173 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed via unconditional logistic regression to evaluate the association between congenital abnormalities and acute leukemia overall, and ALL and AML analyzed separately. The results do not provide evidence for an association among the index children (OR(Combined), 0.74; 95% CI, 0.45-1.23; OR(ALL), 0.67; 95% CI, 0.38-1.20; OR(AML),1.03; 95% CI, 0.49-2.16) or their siblings (OR(Combined), 1.23; 95% CI, 0.71-2.13; OR(ALL), 1.12; 95% CI, 0.60-2.09; OR(AML), 1.60; 95% CI, 0.66-3.86), suggesting congenital malformations do not confer additional risk of leukemia beyond the risk attributable to trisomy 21 in this population. | 18,829,445 |
Expression of epithelial cadherin in the human male reproductive tract and gametes and evidence of its participation in fertilization. | Epithelial cadherin (E-cadherin) has been involved in several calcium-dependent cell-cell adhesion events; however, its participation in gamete interaction has not been fully investigated. Our results have demonstrated expression of E-cadherin mRNA in the human male reproductive tract showing higher levels in the caput, corpus and cauda epididymis than in the testis. The mature 122 kDa E-cadherin was detected in epididymal protein extracts and was localized in the epithelial cells from the three epididymal regions. Moreover, the 86 kDa E-cadherin ectodomain was found in cauda epididymal and seminal plasma. Western immunoblotting of human sperm protein extracts allowed the identification of four E-cadherin forms (122, 105, 97 and 86 kDa). The protein was localized in the acrosomal region of intact spermatozoa, remained associated with the head of acrosome-reacted cells and was also detected on the oocyte surface. A similar localization was determined for other proteins of the adhesion complex (beta-catenin and actin). Spermatozoa incubated with anti-E-cadherin antibodies showed impaired binding to homologous zona pellucida (ZP); in addition, presence of these antibodies inhibited the penetration of human spermatozoa to ZP-free hamster oocytes. The results presented here describe the expression of E-cadherin in the male reproductive tract and gametes and strongly suggest its involvement in adhesion events during human fertilization. The identification of proteins involved in gamete interaction will contribute to the understanding of the molecular basis of fertilization and help in the diagnosis and treatment of infertility. | 18,829,448 |
Phase I study of epigenetic modulation with 5-azacytidine and valproic acid in patients with advanced cancers. | 5-Azacytidine (5-AZA) is a DNA-hypomethylating agent. Valproic acid is a histone deacetylase inhibitor. Combining hypomethylating agents and histone deacetylase inhibitors produces synergistic anticancer activity in vitro and in vivo. On the basis of this evidence, we conducted a phase I study of the combination of 5-AZA and valproic acid in patients with advanced cancers. 5-AZA was administered s.c. daily for 10 days. Valproic acid was given orally daily with a goal to titrate to plasma levels of 75 to 100 mug/mL (therapeutic for seizures). Cycles were 28 days long. 5-AZA was started at 20 mg/m(2) and escalated using an adaptive algorithm based on the toxicity profile in the prior cohort (6 + 6 design). Peripheral blood mononuclear cell global DNA methylation and histone H3 acetylation were estimated with the long interspersed nucleotide elements pyrosequencing assay and Western blots, respectively, on days 1 and 10 of each cycle when patients agreed to provide them. Fifty-five patients were enrolled. Median age was 60 years (range, 12-77 years). The maximum tolerated dose was 75 mg/m(2) of 5-AZA in combination with valproic acid. Dose-limiting toxicities were neutropenic fever and thrombocytopenia, which occurred at a dose of 94 mg/m(2) of 5-AZA. Stable disease lasting 4 to 12 months (median, 6 months) was observed in 14 patients (25%). A significant decrease in global DNA methylation and induction of histone acetylation were observed. The combination of 5-AZA and valproic acid is safe at doses up to 75 mg/m(2) for 5-AZA in patients with advanced malignancies. | 18,829,512 |
Pancreatic stellate cells and pancreatic cancer cells: an unholy alliance. | Pancreatic cancer--a tumor displaying a particularly abundant stromal reaction--is notorious for its poor prognosis. Recent studies, via newly developed orthotopic models, provide compelling evidence of an important role for pancreatic stellate cells (PSC) in pancreatic cancer progression. Characterization of the mechanisms mediating PSC-cancer interactions will lead to the development of much needed alternative therapeutic approaches to improve disease outcome. | 18,829,522 |
The polycomb gene product BMI1 contributes to the maintenance of tumor-initiating side population cells in hepatocellular carcinoma. | Side population (SP) cell analysis and sorting have been successfully applied to hepatocellular carcinoma (HCC) cell lines to identify a minor cell population with cancer stem cell properties. However, the molecular mechanisms operating in SP cells remain unclear. The polycomb gene product BMI1 plays a central role in the self-renewal of somatic stem cells in a variety of tissues and organs and seems to be implicated in tumor development. In this study, we determined the critical role of BMI1 in the maintenance of cancer stem cells with the SP phenotype in HCC cell lines. BMI1 was preferentially expressed in SP cells in Huh7 and PLC/PRF/5 HCC cells compared with the corresponding non-SP cells. Lentiviral knockdown of BMI1 considerably decreased the number of SP cells in both Huh7 and PLC/PRF/5 cells. Long-term culture of purified SP cells resulted in a drastic reduction in the SP subpopulation upon the BMI1 knockdown, indicating that BMI1 is required for the self-renewal of SP cells in culture. More importantly, the BMI1 knockdown abolished the tumor-initiating ability of SP cells in nonobese diabetic/severe combined immunodeficiency mice. Derepression of the INK4A and ARF genes that are major targets for BMI1 was not necessarily associated with impaired self-renewal of SP cells caused by BMI1 knockdown. In conclusion, our findings define an important role for BMI1 in the maintenance of tumor-initiating SP cells in HCC. BMI1 might be a novel therapeutic target for the eradication of cancer stem cells in HCC. | 18,829,528 |
Prolyl isomerase cyclophilin A regulation of Janus-activated kinase 2 and the progression of human breast cancer. | The activation of the Janus-activated kinase 2 (Jak2) tyrosine kinase following ligand binding has remained incompletely characterized at the mechanistic level. We report that the peptidyl-prolyl isomerase (PPI) cyclophilin A (CypA), which is implicated in the regulation of protein conformation, is necessary for the prolactin (PRL)-induced activation of Jak2 and the progression of human breast cancer. A direct correlation was observed between the levels or activity of CypA and the extent of PRL-induced signaling and gene expression. Loss of PRLr-CypA binding, following treatment with the PPI inhibitor cyclosporine A (CsA), or overexpression of a dominant-negative PRLr mutant (P334A) resulted in a loss of PRLr/Jak2-mediated signaling. In vitro, CsA treatment of breast cancer cells inhibited their growth, motility, invasion, and soft agar colony formation. In vivo, CsA treatment of nude mice xenografted with breast cancer cells induced tumor necrosis and completely inhibited metastasis. These studies reveal that a CypA-mediated conformational change within the PRLr/Jak2 complex is required for PRL-induced transduction and function and indicate that the inhibition of prolyl isomerases may be a novel therapeutic strategy in the treatment of human breast cancer. | 18,829,531 |
Heterogeneity of receptor function in colon carcinoma cells determined by cross-talk between type I insulin-like growth factor receptor and epidermal growth factor receptor. | This study identifies a novel cross-talk paradigm between the type I insulin-like growth factor receptor (IGF1R) and epidermal growth factor receptor (EGFR) in colon cancer cells. IGF1R activation by ligand exposure in growth factor-deprived cells induces Akt activation in the FET, CBS, and GEO colon cancer cell lines. Investigation of IGF1R-mediated signaling pathways using small interfering RNA approaches indicated that, as expected, phosphatidylinositol 3'-kinase (PI3K) was activated by IGF1R. Mitogen-activated protein kinase (MAPK) activity as reflected by phospho-extracellular signal-regulated kinase (ERK) induction was not significantly activated until later times following release of these cells from growth factor deprivation stress. The appearance of phospho-ERK was proximal to EGFR activation. Treatment of cells with the PI3K inhibitor LY294002 before release from stress resulted in a concentration-dependent loss of EGFR activation, whereas treatment with the MAPK inhibitor PD98059 did not block EGFR activation, indicating that EGFR activation was downstream of the IGF1R/PI3K pathway. PD98059 inhibition of MAPK was associated with a concentration-dependent reduction in EGFR-mediated phospho-ERK. EGFR inhibitor blocked induction of phospho-ERK, showing that MAPK activity was a consequence of EGFR-mediated signaling. On the other hand, a small-molecule IGF1R inhibitor, PQIP, blocked Akt phosphorylation. The divergent signaling functions of IGF1R and EGFR suggested the potential for synergism by a combination of therapy directed at the two receptors. Combination treatment with PQIP and EGFR inhibitor Tarceva resulted in synergistic effects as indicated by combination index analysis in all three cell lines tested. | 18,829,558 |
The melanoma-associated antigen A3 mediates fibronectin-controlled cancer progression and metastasis. | Tumor cells frequently exhibit decreased adhesiveness due to failure to deposit stromal fibronectin (FN), permitting more rapid proliferation, migration, invasion, and metastasis. Although up-regulation of FN has been noted in gene profiles of carcinomas compared with normal tissue, reduced FN expression has been described at the peripheral margins of invading tumors. In this study, we investigate the role of FN in cancer behavior. Using human thyroid carcinoma cells with stably down-regulated FN, we performed gene profiling and created an orthotopic mouse model. We stably overexpressed the FN target, MAGE A3, which has also been identified as a target of the breast cancer risk factor fibroblast growth factor receptor 2, and examined the functional effects in vitro and in vivo in a flank model and an orthotopic model of thyroid cancer. Mouse xenografts showed significantly enhanced tumor growth as well as larger and more numerous lung metastases in response to FN silencing. Gene profiling identified the melanoma-associated antigen (MAGE A3) as significantly up-regulated in response to FN silencing. Forced expression of MAGE A3 resulted in p21 down-regulation, accelerated cell cycle progression, increased cell migration rate, and invasion in vitro and in vivo in an orthotopic mouse model where microcomputed tomography confirmed lung metastases that recapitulate the progression of human thyroid cancer. We conclude that MAGE A3 is a functional integrator of diverse signals, including FGFR2 and FN, to modulate cancer progression. | 18,829,569 |
Abnormal DNA methylation of CD133 in colorectal and glioblastoma tumors. | Much recent effort has focused on identifying and characterizing cellular markers that distinguish tumor propagating cells (TPC) from more differentiated progeny. We report here an unusual promoter DNA methylation pattern for one such marker, the cell surface antigen CD133 (Prominin 1). This protein has been extensively used to enrich putative cancer propagating stem-like cell populations in epithelial tumors and, especially, glioblastomas. We find that, within individual cell lines of cultured colon cancers and glioblastomas, the promoter CpG island of CD133 is DNA methylated, primarily, in cells with absent or low expression of the marker protein, whereas lack of such methylation is evident in purely CD133+ cells. Differential histone modification marks of active versus repressed genes accompany these DNA methylation changes. This heterogeneous CpG island DNA methylation status in the tumors is unusual in that other DNA hypermethylated genes tested in such cultures preserve their methylation patterns between separated CD133+ and CD133- cell populations. Furthermore, the CD133 DNA methylation seems to constitute an abnormal promoter signature because it is not found in normal brain and colon but only in cultured and primary tumors. Thus, the DNA methylation is imposed on the transition between the active versus repressed transcription state for CD133 only in tumors. Our findings provide additional insight for the dynamics of aberrant DNA methylation associated with aberrant gene silencing in human tumors. | 18,829,568 |
MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. | MicroRNA dysregulation is observed in different types of cancer. MiR-21 up-regulation has been reported for the majority of cancers profiled to date; however, knowledge is limited on the mechanism of action of miR-21, including identification of functionally important targets that contribute to its proproliferative and antiapoptotic actions. In this study, we show for the first time that miR-21 targets multiple important components of the p53, transforming growth factor-beta (TGF-beta), and mitochondrial apoptosis tumor-suppressive pathways. Down-regulation of miR-21 in glioblastoma cells leads to derepression of these pathways, causing repression of growth, increased apoptosis, and cell cycle arrest. These phenotypes are dependent on two of the miR-21 targets validated in this study, HNRPK and TAp63. These findings establish miR-21 as an important oncogene that targets a network of p53, TGF-beta, and mitochondrial apoptosis tumor suppressor genes in glioblastoma cells. | 18,829,576 |
Exogenous irritant-induced airway hyperreactivity and inhibition of soluble guanylyl cyclase. | The majority of nitric oxide (NO) effects in the respiratory system are caused by stimulation of soluble guanylyl cyclase (sGC) with subsequent increase of cyclic guanosine monophosphate (cGMP) production. The importance of this mechanism of NO action in airway hyperreactivity (AHR) pathogenesis is unknown. Therefore, the aim of our experiment was to examine the changes of airway reactivity enhanced by toluene vapor exposure in the presence or inhibition of sGC activity in guinea pigs. Animals were treated with a nonspecific sGC inhibitor, methylene blue, in a dose of 50 or 100 mg/kg body weight, administered by intraperitoneal injection 30 min before or after exposure to toluene vapors. The toluene exposure lasted 2 hr in each of 3 consecutive days under in vivo conditions. Thereafter, the tracheal and lung tissue smooth muscle response to cumulative doses of mediators (histamine or acetylcholine) was recorded under in vitro conditions. The exposure to toluene vapors significantly increased the airway reactivity to both mediators in comparison with the healthy animal group. The administration of methylene blue decreased the amplitude of airway smooth muscle contraction in toluene-induced hyperreactivity. The decreases were dependent on the inhibitor doses, on a regimen of administration (before or after toluene inhalation), the level of the respiratory system (trachea, lung), and the bronchoconstrictor mediators. Our results suggest that the interaction between NO and sGC may be important for airway reactivity changes, but other mechanisms of NO action are important in AHR pathogenesis, too. | 18,829,592 |
Radiofrequency energy delivery to the lower esophageal sphincter (Stretta procedure) does not provide long-term symptom control. | The Stretta procedure (radiofrequency energy application to the lower esophageal sphincter) is a unique endoluminal technique for the management of gastroesophageal reflux. This article reports on the long-term effectiveness of the Stretta procedure in patients with significant gastroesophageal reflux disease (GERD) referred to a surgical practice. Patients who underwent Stretta with a minimum of 36 months follow-up were included. Thirty-two patients with an average follow-up of 53 months were included; 19 proceeded to anti-reflux surgery. Those not undergoing surgery showed a significant improvement in their GERD satisfaction from 3.14 to 1.46 (P = .0006) but had significantly lower preprocedure heartburn scores (2.43) than those who proceeded to surgery (3.66, P = .0401). The Stretta procedure was effective in reducing symptoms in 40% of patients. Responders had less severe preoperative heartburn. Radiofrequency energy delivery to the lower esophageal sphincter may be effective in selected patients for the treatment of gastroesophageal reflux. | 18,829,607 |
Mortality and diabetes mellitus in amputations of the lower limbs for gas gangrene: a case report. | The aim of this study was to examine any association between the presence of diabetes in patients with gas gangrene of the legs and mortality following major lower limb amputation. In a retrospective study, patients submitted to amputation of lower limbs for anaerobic infections were evaluated in the period from January 2005 to January 2007 in the University Hospital de Base in Sao Jose do Rio Preto. All the patients were hospitalized for the treatment of ulcerated lesions of the leg. The study sample consisted of 30 men and 10 women aged between 46 and 87 years (mean 69 years) suffering from anaerobic infections. During treatment, the presence of crepitation in the skin was observed as was gas by radiological examination. Amputation was performed within 2 to 6 hours after diagnosis. Diabetes was identified in 33 patients and death occurred within the perioperative period in 12 cases. Diabetes is associated with the necessity of amputation for gas gangrene resulting in a high mortality rate. | 18,829,608 |
Triple risk: do difficult temperament and family conflict increase the likelihood of behavioral maladjustment in children born low birth weight and preterm? | This study examined the impact of family conflict on internalizing and externalizing behavior at age 8 for children born low birth weight (LBW) and preterm (PT), with specific attention to the moderating role of early temperament. The sample included 728 families enrolled in the longitudinal study of the Infant Health and Development Program. The study relied on maternal reports of child temperament at age 1, family conflict at age 6(1/2) years and 8 years, and child behavior at age 8 years. Children exposed to high levels of family conflict had more internalizing problems. Child temperament assessed in infancy moderated the impact of family conflict on externalizing but not internalizing problem behavior. LBW/PT children with a difficult temperament are more at risk for poor developmental outcomes, such as externalizing behavior problems, when exposed to family conflict than children with a less difficult temperament. | 18,829,612 |
Neural respiratory drive in healthy subjects and in COPD. | The aim of the present study was to use the diaphragm electromyogram (EMG(di)) to compare levels of neural respiratory drive (NRD) in a cohort of healthy subjects and chronic obstructive pulmonary disease (COPD) patients, and to investigate the relationship between NRD and pulmonary function in COPD. EMG(di) was recorded at rest and normalised to peak EMG(di) recorded during maximum inspiratory manoeuvres (EMG(di) % max) in 100 healthy subjects and 30 patients with COPD, using a multipair oesophageal electrode. EMG(di) was normalised to the amplitude of the diaphragm compound muscle action potential (CMAP(di,MS)) in 64 healthy subjects. The mean+/-sd EMG(di) % max was 9.0+/-3.4% in healthy subjects and 27.9+/-9.9% in COPD patients, and correlated with percentage predicted forced expiratory volume in one second, vital capacity and inspiratory capacity in patients. EMG(di) % max was higher in healthy subjects aged 51-80 yrs than in those aged 18-50 yrs (11.4+/-3.4 versus 8.2+/-2.9%, respectively). Observations in the healthy group were similar when peak EMG(di) or CMAP(di,MS) were used to normalise EMG(di). Levels of neural respiratory drive were higher in chronic obstructive pulmonary disease patients than healthy subjects, and related to disease severity. Diaphragm compound muscle action potential could be used to normalise diaphragm electromyogram if volitional inspiratory manoeuvres could not be performed, allowing translation of the technique to critically ill and ventilated patients. | 18,829,678 |
Hypothalamic involvement in Huntington's disease: an in vivo PET study. | Recent studies have shown alterations in metabolism, sleep and circadian rhythms as well as in several neuropeptides derived from the hypothalamic-pituitary axis in Huntington's disease patients; however, the pathology underlying these abnormalities is not known. Our aim was to assess in vivo D(2) receptor's loss/dysfunction and increases in microglial activation in the hypothalamus of symptomatic Huntington's disease patients and premanifest Huntington's disease gene carriers using PET with (11)C-raclopride (RAC), a specific D(2) receptor ligand and (11)C-(R)-PK11195 (PK), a marker of microglial activation. We have studied 9 symptomatic Huntington's disease patients (age = 46.8 +/- 4.7 years; mean +/- SD) and 10 premanifest Huntington's disease gene carriers (age = 41.9 +/- 8.2 years; mean +/- SD). RAC and PK findings for these subjects were compared with those of a group of normal controls (RAC, n = 9; PK, n = 10). In the symptomatic Huntington's disease group, we found a significant decrease (P = 0.0012) in mean hypothalamic RAC binding potential (BP) and a significant increase in mean hypothalamic PK BP (P = 0.0008). Similarly, a significant decrease (P = 0.0143) in mean hypothalamic RAC BP and a significant increase in mean hypothalamic PK BP (P = 0.0057) were observed in the premanifest Huntington's disease group. Hypothalamic RAC and PK BP values correlated with each other in combined Huntington's disease groups (r = -0.6180, P = 0.0048) but not with striatal RAC and PK BP values. Our data demonstrate, for the first time, significant D(2) receptor loss and microglia activation in the hypothalamus of Huntington's disease. These pathological changes occur very early in the course of the disease and may partly explain the development of commonly reported symptoms in Huntington's disease including progressive weight loss, alterations in sexual behaviour and disturbances in the wake-sleep cycle. | 18,829,696 |
Proteomic analysis of scleroderma lesional skin reveals activated wound healing phenotype of epidermal cell layer. | To identify using proteomic analysis, proteins of altered abundance in the skin of patients with SSc. 4 mm excision biopsies were obtained from the forearm involved skin of 12 diffuse SSc patients and 12 healthy controls. Two-dimensional gel electrophoresis was used to separate and define proteins in normal and SSc skin biopsy material. Proteins of altered abundance in the disease were formally identified by mass spectroscopy. Abnormalities of the epidermis were confirmed by immunohistochemistry. Proteomic analysis revealed altered abundance of proteins involved in extracellular matrix production, myofibroblast contractility, energy metabolism and response to oxidative stress. In addition, proteins specific to the epidermis and involved in epidermal cell differentiation were altered in abundance in the disease. SSc epidermis is thickened, has an expanded nucleated cell layer, and exhibits abnormal persistence of basal marker keratin 14, delayed expression of maturation markers keratin 1/10 and the induction of keratins 6 and 16, normally absent from interfollicular skin and induced following epidermal injury. These changes closely resemble the activated phenotype seen during wound healing. Consistent with previous models of SSc pathogenesis these data are showing increased contractility, increased extracellular matrix and response to oxidative stress in the involved skin of recent onset SSc patients. In addition, we show that SSc epidermis has an activated, wound healing phenotype. These findings are important because epidermal cells activated by injury induce and regulate local fibroblasts during wound repair. | 18,829,709 |
S-adenosyl homocysteine-induced hyperpolyadenylation of vesicular stomatitis virus mRNA requires the methyltransferase activity of L protein. | There are many unique aspects of vesicular stomatitis virus (VSV) transcription. In addition to its unusual mRNA capping and methyltransferase mechanisms, the addition of S-adenosyl homocysteine (SAH), which is the by-product and competitive inhibitor of S-adenosyl methionine (SAM)-mediated methyltransferase reactions, leads to synthesis of poly(A) tails on the 3' end of VSV mRNAs that are 10- or 20-fold longer than normal. The mechanism by which this occurs is not understood, since it has been shown that productive transcription is not dependent on 5' cap methylation and full-length VSV mRNAs can be synthesized in the absence of SAM. To investigate this unusual phenotype, we assayed the effects of SAH on transcription using a panel of recombinant viruses that contained mutations in domain VI of the VSV L protein. The L proteins we investigated displayed a range of 5' cap methyltransferase activities. In the present study, we show that the ability of the VSV L protein to catalyze methyl transfer correlates with its sensitivity to SAH with respect to polyadenylation, thereby indicating an intriguing connection between 5' and 3' end mRNA modifications. We also identified an L protein mutant that hyperpolyadenylates mRNA irrespective of the presence or absence of exogenous SAH. Further, the data presented here show that the wild-type L protein hyperpolyadenylates a percentage of VSV mRNAs in infected cells as well as in vitro. | 18,829,753 |
Experimental evolution of human influenza virus H3 hemagglutinin in the mouse lung identifies adaptive regions in HA1 and HA2. | The genetic basis for virulence and host switching in influenza A viruses (FLUAV) is largely unknown. Because the hemagglutinin (HA) protein is a determinant of these properties, HA evolution was mapped in an experimental model of mouse lung adaptation. Variants of prototype A/Hong Kong/1/68 (H3N2) (wild-type [wt] HK) human virus were selected in both longitudinal and parallel studies of lung adaptation. Mapping of HA mutations found in 11 independently derived mouse-adapted populations of wt HK identified 27 mutations that clustered within two distinct regions in or near the globular frameworks of the HA1 and HA2 subunits. The adaptive mutations demonstrated multiple instances of convergent evolution involving four amino acid positions (162, 210, and 218 in HA1 and 154 in HA2). By use of reverse genetics, convergent HA mutations were shown to affect cell tropism by enhancing infection and replication in primary mouse tracheal epithelial cells in vitro and mouse lung tissue in vivo. Adaptive HA mutations were multifunctional, affecting both median pH of fusion and receptor specificity. Specific mutations within both adaptive regions were shown to increase virulence in a mouse lung model. The occurrence of mutations in the HA1 and HA2 adaptive regions of natural FLUAV host range and virulent variants of avian and mammalian viruses is discussed. This study has identified adaptive sites and regions within the HA1 and HA2 subunits that may guide future studies of viral adaptation and evolution in nature. | 18,829,764 |
Systematic review of digital imaging screening strategies for retinopathy of prematurity. | Retinal imaging with remote interpretation could decrease the number of diagnostic eye examinations that premature infants need for the detection of retinopathy of prematurity and thus decrease the time demand on the relatively small pool of ophthalmologists who perform retinopathy of prematurity examinations. Our goal was to review systematically the evidence regarding the reliability, validity, safety, costs, and benefits of retinal imaging to screen infants who are at risk for retinopathy of prematurity. We searched Medline, the Cochrane library, CINAHL, and the bibliographies of all relevant articles. All English-language studies regardless of design with primary data about our study questions were included. We excluded (1) studies that only included subjects with retinopathy of prematurity, (2) hypothetical models other than cost-effectiveness studies, and (3) validity studies without sufficient data to determine prevalence, sensitivity, and specificity or that only evaluated subjects for 1 component of retinopathy of prematurity (eg, plus disease only). Studies of only 1 retinal imaging device (RetCam [Clarity Medical Systems, Inc, Pleasanton, CA]) met the inclusion criteria. There was a wide range in reported sensitivity, but specificity was high. There were several important limitations noted, including the eye as the unit of analysis instead of the individual or variations in the criteria for determining a true-positive or true-negative screening result. The risk of retinal hemorrhage resulting from imaging is low, and systemic effects (eg, bradycardia, hypertension, decreased oxygen saturation) are mild. No generalizable cost-effectiveness data were found. The evidence base is not sufficient to recommend that retinal imaging be routinely adopted by NICUs to identify infants who have serious retinopathy of prematurity. | 18,829,807 |
Medical emergencies occurring at school. | Children and adults might experience medical emergency situations because of injuries, complications of chronic health conditions, or unexpected major illnesses that occur in schools. In February 2001, the American Academy of Pediatrics issued a policy statement titled "Guidelines for Emergency Medical Care in Schools" (available at: http://aappolicy.aappublications.org/cgi/content/full/pediatrics;107/2/435). Since the release of that statement, the spectrum of potential individual student emergencies has changed significantly. The increase in the number of children with special health care needs and chronic medical conditions attending schools and the challenges associated with ensuring that schools have access to on-site licensed health care professionals on an ongoing basis have added to increasing the risks of medical emergencies in schools. The goal of this statement is to increase pediatricians' awareness of schools' roles in preparing for individual student emergencies and to provide recommendations for primary care and school physicians on how to assist and support school personnel. | 18,829,817 |
Toward optimal target placement for neural prosthetic devices. | Neural prosthetic systems have been designed to estimate continuous reach trajectories (motor prostheses) and to predict discrete reach targets (communication prostheses). In the latter case, reach targets are typically decoded from neural spiking activity during an instructed delay period before the reach begins. Such systems use targets placed in radially symmetric geometries independent of the tuning properties of the neurons available. Here we seek to automate the target placement process and increase decode accuracy in communication prostheses by selecting target locations based on the neural population at hand. Motor prostheses that incorporate intended target information could also benefit from this consideration. We present an optimal target placement algorithm that approximately maximizes decode accuracy with respect to target locations. In simulated neural spiking data fit from two monkeys, the optimal target placement algorithm yielded statistically significant improvements up to 8 and 9% for two and sixteen targets, respectively. For four and eight targets, gains were more modest, as the target layouts found by the algorithm closely resembled the canonical layouts. We trained a monkey in this paradigm and tested the algorithm with experimental neural data to confirm some of the results found in simulation. In all, the algorithm can serve not only to create new target layouts that outperform canonical layouts, but it can also confirm or help select among multiple canonical layouts. The optimal target placement algorithm developed here is the first algorithm of its kind, and it should both improve decode accuracy and help automate target placement for neural prostheses. | 18,829,845 |
Munc18a scaffolds SNARE assembly to promote membrane fusion. | Munc18a is an SM protein required for SNARE-mediated fusion. The molecular details of how Munc18a acts to enhance neurosecretion have remained elusive. Here, we use in vitro fusion assays to characterize how specific interactions between Munc18a and the neuronal SNAREs enhance the rate and extent of fusion. We show that Munc18a interacts directly and functionally with the preassembled t-SNARE complex. Analysis of Munc18a point mutations indicates that Munc18a interacts with helix C of the Syntaxin1a NRD in the t-SNARE complex. Replacement of the t-SNARE SNAP25b with yeast Sec9c had little effect, suggesting that Munc18a has minimal contact with SNAP25b within the t-SNARE complex. A chimeric Syntaxin built of the Syntaxin1a NRD and the H3 domain of yeast Sso1p and paired with Sec9c eliminated stimulation of fusion, suggesting that Munc18a/Syntaxin1a H3 domain contacts are important. Additionally, a Syntaxin1A mutant lacking a flexible linker region that allows NRD movement abolished stimulation of fusion. These experiments suggest that Munc18a binds to the Syntaxin1a NRD and H3 domain within the assembled t-SNARE complex, positioning them for productive VAMP2 binding. In this capacity, Munc18a serves as a platform for trans-SNARE complex assembly that facilitates efficient SNARE-mediated membrane fusion. | 18,829,865 |
Patients with workers' compensation claims have worse outcomes after rotator cuff repair. | Previous studies have demonstrated varying correlations between Workers' Compensation status and the outcome of rotator cuff repair. However, none of those studies have formally accounted for potential confounding factors with multivariable analysis. We hypothesized that patients with Workers' Compensation claims who undergo rotator cuff repair have worse outcomes, even after controlling for confounding factors. One hundred and twenty-five patients (including thirty-nine with Workers' Compensation claims) who underwent unilateral primary repair of a chronic rotator cuff tear by a single surgeon were studied prospectively and were evaluated one year postoperatively, prior to the settlement of any claims. Outcomes were assessed with the Simple Shoulder Test (SST); the Disabilities of the Arm, Shoulder and Hand (DASH) index; three visual analog scales (shoulder pain, shoulder function, and quality of life); and the Short Form-36 (SF-36). Patients in the Workers' Compensation group were significantly younger, had greater work demands, and had lower marital rates, education levels, and preoperative expectations for the outcome of treatment as compared with those in the non-Workers' Compensation group (p = 0.001 to 0.016). Preoperatively, patients in the Workers' Compensation group had significantly lower scores on the SST, the SF-36 Physical Function scale, and the SF-36 Social Function scale (p = 0.01 to 0.038). One year postoperatively, those patients reported worse performance on the SST, the DASH, all three visual analog scales, and the SF-36 (p = 0.0007 to 0.05) and had worse improvement on the DASH, the visual analog scales for shoulder pain and function, and the SF-36 Bodily Pain and Role Emotional scales (p = 0.0028 to 0.038). Multivariable analysis controlling for age, sex, comorbidities, smoking, marital status, education, duration of symptoms, work demands, expectations, and tear size confirmed that Workers' Compensation status was an independent predictor of worse DASH scores. Patients with Workers' Compensation claims report worse outcomes, even after controlling for confounding factors. The present study provides further evidence that the existence of a Workers' Compensation claim portends a less robust outcome following rotator cuff repair. Prognostic Level I. See Instructions to Authors for a complete description of levels of evidence. | 18,829,907 |
Prophylactic bypass grafting and long-term bracing in the management of anterolateral bowing of the tibia and neurofibromatosis-1. | Congenital anterolateral bowing of the tibia is a pre-pseudarthrosis stage of congenital pseudarthrosis of the tibia and is associated with a substantial risk of fracture and pseudarthrosis. We evaluated the results of prophylactic bypass grafting performed in combination with bracing to prevent fracture and pseudarthrosis. This retrospective series included ten patients with pre-pseudarthrosis of the tibia treated, between 1991 and 2002, with prophylactic bypass grafting with an allograft fibula placed posteromedially in a stress-bearing fashion. The average patient age was 2.3 years at the time of diagnosis, 3.6 years at the time of surgery, and ten years at the time of final follow-up. The mean duration of follow-up was seventy-eight months. Brace protection was recommended at the time of diagnosis and was continued after the operation until maturity. Despite the bracing, a low-energy fracture developed and partially healed prior to the bypass grafting in one patient. The remaining nine patients had no fractures prior to the bypass grafting. At the time of final follow-up, the patients were examined clinically and radiographically for the presence of a fracture or pseudarthrosis and for residual deformity, including malalignment, ankle and knee joint abnormalities, and leg length discrepancy. No patient had either a fracture or a pseudarthrosis of the tibia at the time of follow-up. All grafts united to the tibia at both ends. Complications included an allograft fracture in three patients, which healed in all; allograft resorption in one patient; and pseudarthrosis of the ipsilateral host fibula in one patient. At the time of final follow-up, a mean of 9 mm (range, 0 to 37 mm) of leg length discrepancy was found. A corrective osteotomy was done for four patients (three because of ankle valgus and one because of diaphyseal deformity). In this small series of ten patients with congenital anterolateral bowing of the tibia treated with bypass strut grafting and long-term bracing, there were no cases of pseudarthrosis of the tibia. Distal tibial deformity may persist throughout the growth period and require operative correction in patients treated with this procedure. Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence. | 18,829,910 |
Surgical treatment of calcaneal deformity in a select group of patients with myelomeningocele. | The surgical treatment of calcaneal deformity in patients with myelomeningocele has not been uniformly successful in correcting the deformity and preventing recurrence. The purpose of the present study was to examine the results of posterior transfer of the anterior tibial tendon with concurrent procedures in an attempt to balance the muscular forces on the foot and ankle and to obtain a plantigrade foot. We investigated whether surgery improved pressure distribution over the plantar surface of the foot and whether concurrent abnormal movements observed at the knee, hip, and pelvis influenced the surgical outcome. Thirty-one feet in eighteen patients who were able to walk were included in the study. The mean age at the time of surgery was seven years and four months, and the mean duration of follow-up was forty-seven months. Eight patients were classified as having an L5-level myelomeningocele, and ten patients were classified as having a sacral level myelomeningocele. A tibialis anterior tendon transfer was performed in all patients, and accompanying osseous deformities were also corrected in twelve feet. Measurements on plain radiographs, the results of gait analyses, and dynamic foot pressures that were determined before surgery and at the time of the final follow-up were compared. No recurrence or worsening of the deformity was observed in any of the patients, and no other types of foot deformity developed after surgery. Postoperative kinematic studies showed a significant (p < 0.0001) increase in peak plantar flexion and a significant decrease in peak dorsiflexion force of the ankle in the stance phase of gait. Peak pressures under the forefoot and midfoot were increased after surgery, and the relative amount of weight-bearing on the heel as compared with the forefoot was shifted toward more equal weight-bearing. However, less improvement in foot-pressure distribution was observed in patients with increased pelvic rotation before surgery. Those patients also had decreased knee extension in stance phase and increased hip abduction and pelvic obliquity both before and after surgery in comparison with patients who had normal pelvic rotation. Appropriately combined corrective surgical procedures for the treatment of calcaneal deformity in patients with myelomeningocele can effectively reduce the pressure placed on the calcaneus, increase pressures in the forefoot and midfoot, and prevent recurrence of the calcaneal deformity. However, in the presence of excessive pelvic movement in the coronal and transverse planes and decreased knee extension in stance phase, adequate improvement in pressure distribution over the plantar surface of the foot is not likely to occur after this type of foot surgery. Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence. | 18,829,913 |
Distal tibial reconstruction with use of a circular external fixator and an intramedullary nail. Surgical technique. | Distal tibial reconstruction with use of an external fixator when there is bone loss, limb-length discrepancy, and/or ankle instability is associated with many problems. The technique of limb-lengthening, ankle arthrodesis, and segmental transfer over an intramedullary nail has been introduced to overcome these problems. The present study investigates this combined technique. Between 2002 and 2005, six patients, who ranged from seventeen to seventy years old, underwent distal tibial reconstruction and ankle arthrodesis with use of a circular external fixator and an intramedullary nail to treat a distal tibial defect following resection for chronic osteomyelitis or tumor or to treat a limb-length discrepancy combined with ankle instability. Functional and radiographic results were evaluated, with use of the criteria described by Paley et al., at an average follow-up of thirty-four months. The mean size of the bone defect in three patients was 5.3 cm (2, 7, and 7 cm), and the mean amount of the limb-shortening in four patients was 5.25 cm (range, 4 to 6 cm). The mean external fixation time was 3.5 months, and the mean external fixator index was 0.57 mo/cm. There was no recurrence of infection in the two patients with osteomyelitis. All six patients had excellent bone results, and the functional results were excellent for two patients and good for four patients. There were four complications, three of which were categorized, according to Paley, as a problem (a difficulty that occurs during lengthening and is resolved without operative intervention) and one that was categorized as an obstacle (a difficulty that occurs during lengthening and needs operative treatment). The combined technique is an improvement over the classic external fixation techniques of distal tibial reconstruction with ankle arthrodesis. It reduces the duration of external fixation, thus increasing patient acceptance, and it is associated with a low complication rate facilitating more rapid rehabilitation. | 18,829,932 |
Drosophila painless is a Ca2+-requiring channel activated by noxious heat. | Thermal changes activate some members of the transient receptor potential (TRP) ion channel super family. They are primary sensors for detecting environmental temperatures. The Drosophila TRP channel Painless is believed responsible for avoidance of noxious heat because painless mutant flies display defects in heat sensing. However, no studies have proven its heat responsiveness. We show that Painless expressed in human embryonic kidney-derived 293 (HEK293) cells is a noxious heat-activated, Ca(2+)-permeable channel, and the function is mostly dependent on Ca(2+). In Ca(2+)-imaging, Painless mediated a robust intracellular Ca(2+) (Ca(2+)(i)) increase during heating, and it showed heat-evoked inward currents in whole-cell patch-clamp mode. Ca(2+) permeability was much higher than that of other cations. Heat-evoked currents were negligible in the absence of extracellular Ca(2+) (Ca(2+)(o)) and Ca(2+)(i), whereas 200 nm Ca(2+)(i) enabled heat activation of Painless. Activation kinetics were significantly accelerated in the presence of Ca(2+)(i). The temperature threshold for Painless activation was 42.6 degrees C in the presence of Ca(2+)(i), whereas the threshold was significantly increased to 44.1 degrees C when only Ca(2+)(o) was present. Temperature thresholds were further reduced after repetitive heating in a Ca(2+)-dependent manner. Ca(2+)-dependent heat activation of Painless was observed at the single-channel level in excised membranes. We found that a Ca(2+)-regulatory site is located in the N-terminal region of Painless. Painless-expressing HEK293 cells were insensitive to various thermosensitive TRP channel activators including allyl isothiocyanate, whereas mammalian TRPA1 inhibitors, ruthenium red, and camphor, reversibly blocked heat activation of Painless. Our results demonstrate that Painless is a direct sensor for noxious heat in Drosophila. | 18,829,951 |
Perceptual systems controlling speech production. | It is proposed that the acquisition and maintenance of fluent speech depend on the rapid temporal integration of motor feedforward and polysensory (auditory and somatosensory) feedback signals. In a functional magnetic resonance imaging study on 21 healthy right-handed, English-speaking volunteers, we investigated activity within these motor and sensory pathways and their integration during speech. Four motor conditions were studied: two speech conditions (propositional and nonpropositional speech) and two silent conditions requiring repetitive movement of the principal articulators (jaw and tongue movements). The scanning technique was adapted to minimize artifact associated with overt speech production. Our result indicates that this multimodal convergence occurs within the left and right supratemporal planes (STPs), with peaks of activity at their posteromedial extents, in regions classically considered as unimodal auditory association cortex. This cortical specialization contrasted sharply with the response of somatosensory association cortex (SII), in which activity was suppressed during speech but not during the silent repetitive movement of the principal articulators. It was also clearly distinct from the response of lateral auditory association cortex, which responded to auditory feedback alone, and from that within a left lateralized ventrolateral temporal and inferior frontal system, which served lexical- and sentence-level language retrieval. This response of cortical regions related to speech production is not predicted by the classical model of hierarchical cortical processing, providing new insights into the role of the STP in polysensory integration and into the modulation of activity in SII during normal speech production. These findings have novel implications for the acquisition and maintenance of fluent speech. | 18,829,954 |
Does learned shape selectivity in inferior temporal cortex automatically generalize across retinal position? | Biological visual systems have the remarkable ability to recognize objects despite confounding factors such as object position, size, pose, and lighting. In primates, this ability likely results from neuronal responses at the highest stage of the ventral visual stream [inferior temporal cortex (IT)] that signal object identity while tolerating these factors. However, for even the apparently simplest IT tolerance ("invariance"), tolerance to object position on the retina, little is known about how this feat is achieved. One possibility is that IT position tolerance is innate in that discriminatory power for newly learned objects automatically generalizes across position. Alternatively, visual experience plays a role in developing position tolerance. To test these ideas, we trained adult monkeys in a difficult object discrimination task in which their visual experience with novel objects was restricted to a single retinal position. After training, we recorded the spiking activity of an unbiased population of IT neurons and found that it contained significantly greater selectivity among the newly learned objects at the experienced position compared with a carefully matched, non-experienced position. Interleaved testing with other objects shows that this difference cannot be attributed to a bias in spatial attention or neuronal sampling. We conclude from these results that, at least under some conditions, full transfer of IT neuronal selectivity across retinal position is not automatic. This finding raises the possibility that visual experience plays a role in building neuronal tolerance in the ventral visual stream and the recognition abilities it supports. | 18,829,962 |
A local circuit model of learned striatal and dopamine cell responses under probabilistic schedules of reward. | Recently, dopamine (DA) neurons of the substantia nigra pars compacta (SNc) were found to exhibit sustained responses related to reward uncertainty, in addition to the phasic responses related to reward-prediction errors (RPEs). Thus, cue-dependent anticipations of the timing, magnitude, and uncertainty of rewards are learned and reflected in components of DA signals. Here we simulate a local circuit model to show how learned uncertainty responses are generated, along with phasic RPE responses, on single trials. Both types of simulated DA responses exhibit the empirically observed dependencies on conditional probability, expected value of reward, and time since onset of the reward-predicting cue. The model's three major pathways compute expected values of cues, timed predictions of reward magnitudes, and uncertainties associated with these predictions. The first two pathways' computations refine those modeled by Brown et al. (1999). The third, newly modeled, pathway involves medium spiny projection neurons (MSPNs) of the striatal matrix, whose axons corelease GABA and substance P, both at synapses with GABAergic neurons in the substantia nigra pars reticulata (SNr) and with distal dendrites (in SNr) of DA neurons whose somas are located in ventral SNc. Corelease enables efficient computation of uncertainty responses that are a nonmonotonic function of the conditional probability of reward, and variability in striatal cholinergic transmission can explain observed individual differences in the amplitudes of uncertainty responses. The involvement of matricial MSPNs and cholinergic transmission within the striatum implies a relation between uncertainty in cue-reward contingencies and action-selection functions of the basal ganglia. | 18,829,964 |
Intracellular angiotensin II production in diabetic rats is correlated with cardiomyocyte apoptosis, oxidative stress, and cardiac fibrosis. | Many of the effects of angiotensin (Ang) II are mediated through specific plasma membrane receptors. However, Ang II also elicits biological effects from the interior of the cell (intracrine), some of which are not inhibited by Ang receptor blockers (ARBs). Recent in vitro studies have identified high glucose as a potent stimulus for the intracellular synthesis of Ang II, the production of which is mainly chymase dependent. In the present study, we determined whether hyperglycemia activates the cardiac intracellular renin-Ang system (RAS) in vivo and whether ARBs, ACE, or renin inhibitors block synthesis and effects of intracellular Ang II (iAng II). Diabetes was induced in adult male rats by streptozotocin. Diabetic rats were treated with insulin, candesartan (ARB), benazepril (ACE inhibitor), or aliskiren (renin inhibitor). One week of diabetes significantly increased iAng II levels in cardiac myocytes, which were not normalized by candesartan, suggesting that Ang II was synthesized intracellularly, not internalized through AT(1) receptor. Increased intracellular levels of Ang II, angiotensinogen, and renin were observed by confocal microscopy. iAng II synthesis was blocked by aliskiren but not by benazepril. Diabetes-induced superoxide production and cardiac fibrosis were partially inhibited by candesartan and benazepril, whereas aliskiren produced complete inhibition. Myocyte apoptosis was partially inhibited by all three agents. Diabetes activates the cardiac intracellular RAS, which increases oxidative stress and cardiac fibrosis. Renin inhibition has a more pronounced effect than ARBs and ACE inhibitors on these diabetes complications and may be clinically more efficacious. | 18,829,990 |
Thermodynamic properties of blood plasma of patient suffering from atherosclerosis. | The goal of the work is to find out the changes in the heat parameters of blood plasma denaturation of a son and a granddaughter, in comparison with the same parameters of a 91 years old grandfather with atherosclerosis. The significant changes in heat (Q(d)) and denaturation temperature (T(d)) of albumin, globulins and fibrinogen of 91-year-old patient suffering from atherosclerosis relative to the norm (88-year-old man) are found out. In particular, Q(d) increase by 60% of albumin fat fraction and fibrinogen of F domain and the increase of their T(d) by 2.4 degrees C and 2.8 degrees C relative to the norm; Q(d) decrease by 1.8 times and T(d) increase by 2.9 degrees C of gamma globulin relative to the norm; Q(d) decrease by 6 time of D domain fibrinogen and and globulins by 1.4 and 2.9 times relative to the norm. Total denaturation heat of donor blood plasma is equal to 25.5+/-3 J/g and patient suffering from atherosclerosis is equal to 22.0 J/g. The most significant changes of heat parameters are observed between grandfather and granddaughter: an increase of D domain T(d) by 4 degrees C and Q(d) by 6 times; T(d) increase of albumin fat fraction by 4.3 degrees C and its Q(d) decrease by 10% of granddaughter in comparison with her grandfather. As value Qd of proteins is directly proportional to protein concentration in solutions, we conclude that the significant changes of concentration main proteins in blood plasma and changes of their thermodynamic stability occur at atherosclerosis, relative to the norm. | 18,830,024 |
[Calcitonin]. | Calcitonin is a polypeptide hormone that bone resorption-inhibitory and analgesic effects, and has been used over many decades as a drug for the treatment of osteoporosis in Japan and overseas. Reports of large-scale studies of this hormone therefore as yet are few, compared to recently introduced drugs. Calcitonin is prescribed in injectable form in Japan while nasal spray preparations are widely used in Europe and the Unites States. Its characteristic effect of analgesia is slow in onset as compared with anti-inflammatory analgesic agents. A mechanism of action involving its serotonin receptor expression-mediated effect on pain impulse transmission has been demonstrated. On account of this effect, calcitonin is recommended for use in the management of pain in patients with fresh vertebral fractures. | 18,830,043 |
High levels of antibodies to Plasmodium falciparum liver stage antigen-1 in naturally infected individuals in Myanmar. | Plasmodium falciparum liver stage antigen-1 (PfLSA-1) is one of the few antigens expressed exclusively in liver stage parasites. In this study, we evaluated the antibody responses against recombinant PfLSA-1 in naturally infected individuals in Myanmar. High levels of antibody responses (70.7%) were detected in 82 serum samples from 116 infected individuals, and IgG responses to PfLSA-1 principally composed of responses of IgG1 and IgG3 subclasses. These results show that PfLSA-1 elicits effective antibody responses in individuals infected with P. falciparum, and thus it could be not only an attractive candidate protein for vaccine development, but also a useful antigen for serodiagnosis of the infection. | 18,830,063 |
Contemporary management of fibromuscular dysplasia. | Fibromuscular dysplasia is an underdiagnosed and misunderstood disease. The purpose of this review is to inform healthcare providers and the public about a condition that may be more common than previously thought. There has been little new information published about fibromuscular dysplasia in the past 30 years. The International Registry that is now underway will remedy that situation and provide a large number of patients to study with this condition. Fibromuscular dysplasia is a noninflammatory, nonatherosclerotic disease that has been reported in almost every arterial bed and primarily affects women aged 15-50 years. It most commonly presents in the renal and extracranial cerebrovascular arteries, either manifesting as hypertension, transient ischemic attack or stroke, respectively. Some patients may be asymptomatic and fibromuscular dysplasia could only be discovered by imaging for some other reason or by the detection of an asymptomatic bruit. Dissection or aneurysm may also occur in patients with fibromuscular dysplasia. The true prevalence is unknown, partially because of the fact that it is underdiagnosed in many patients. Treatment consists of antiplatelet therapy for asymptomatic individuals and percutaneous balloon angioplasty for patients with indications for intervention. Patients with macroaneurysms should be treated with either a covered stent or surgery. | 18,830,066 |
Predicting outcomes in cardiac surgery: risk stratification matters? | To illustrate the limitations of predictive risk models in cardiac surgery, highlight the difficulty in interpreting risk-adjusted outcome analysis and discuss the challenges of making clinical decisions based on risk predictions, particularly in high-risk patients. Predictive risk models developed after logistic regression or other complex statistical analysis are commonly perceived as rigorous means to determine risk-adjusted mortality in cardiac surgery. However, the discrimination provided by those predictive models is barely better than clinical judgment. Moreover, validation studies of those models show that their calibration is inconsistent, limiting their application for comparisons between different patient cohorts. Recent data also show that, without a reasonable overlap of case-mix distributions, apparently calibrated models used for risk-adjusted outcome analysis may lead to inaccurate side-by-side comparisons of provider performance. Finally, most predictive models overestimate risk, particularly in the high-risk patients. Failure to account for many biological and procedural variables and for the constantly evolving practice of surgery and perioperative medicine likely contributes to the modest predictive performance of risk models in cardiac surgery. Consequently, those models should have limited input in the analysis of provider performance and in the decision to accept or deny surgery to the high-risk patients. | 18,830,070 |
Intraoperative coronary graft assessment. | Intraoperative graft assessment in coronary artery bypass grafting is infrequently performed. Nevertheless, studies show an immediate graft closure rate of 5-9% and a 1-year closure rate of 20-30%. Coronary angiography is the 'gold standard' for graft assessment yet has been seldom employed because of logistical problems and image quality. Two methods, transit time flow measurement and intraoperative fluorescence imaging are simple, safe, and expeditious. Intraoperative graft failure detection rates of 2-5% have been reported. Early graft occlusion occurs frequently after coronary artery bypass grafting. Two relatively simple but underutilized methods of intraoperative graft assessment have been shown to be predictive of graft failure. Wider use of these techniques as well as wider availability of hybrid operating rooms, which will allow intraoperative coronary angiography, may reduce graft failure. | 18,830,071 |
Distribution of body fat and risk of coronary heart disease in men and women. | Earlier studies investigating the risk of developing coronary heart disease in relation to body fat distribution showed inconsistent results, and any sex-related difference in disease risk has not been adequately examined. This review aims to assess current findings on the prospective association between body fat distribution measures and coronary heart disease in men and women. Current epidemiologic evidence suggests that waist circumference and waist-hip ratio, as indicators of abdominal adiposity, are positively related to coronary heart disease in men and women independently of body mass index and conventional coronary heart disease risk factors. But the magnitude and shape of the associations for these abdominal adiposity indices varied with adjustments for mediating and confounding factors. Interestingly, hip waist circumference was inversely associated with coronary heart disease after adjusting for waist circumference. Because waist and hips are positively correlated but have separate and opposite associations with coronary disease, using waist circumference alone may provide underestimated risk estimate if hip girth is not accounted for in the calculation of this risk. For adipose tissue distribution assessment to be clinically useful, the ideal adiposity phenotype should provide a single risk estimate that captures the separate 'effects' of abdominal and peripheral adiposity. Although far from perfect, waist-hip ratio may capture separate effects of central and peripheral adiposity. This simple and inexpensive measure could be used to help improve coronary heart disease risk assessment. | 18,830,075 |
A customized genetic approach to the number one killer: coronary artery disease. | To review the evidence supporting genetic predisposition to coronary artery disease (CAD). Secondly, to elucidate the barriers precluding the identification of genes responsible for CAD. Thirdly, to indicate the new technology now available to overcome these barriers and summarize current progress. Evidence strongly supports that 50% of susceptibility to CAD is genetic. Prevention of CAD requires comprehensive genetic and risk factor modification. Technology to perform genome-wide association studies became available in 2005, namely, the microarrays with 500,000 and 1 million single nucleotide polymorphisms as DNA markers for high-throughput genotyping to determine gene frequencies in large datasets of cases and controls. The first genetic variant, 9p21, for CAD was identified in the Ottawa Heart Genomic study. This is not only a genetic risk factor but also independent of other known risk factors for CAD. 9p21 was subsequently confirmed as a risk variant in several other independent studies involving 64 000 Caucasians. 9p21 increases the risk of CAD by 40% and 20% in heterozygous or homozygous forms respectively. It occurs in 75% of Caucasians, and has recently been confirmed in several other ethnic groups. Thus, identification of predisposition to CAD is well underway with genome-wide association studies and the first common genetic risk variant, 9p21, has been identified. | 18,830,080 |
Left atrial calcifications: computed tomographic imaging findings of an unusual sign of rheumatic heart disease. | Left atrial wall calcifications are an extremely rare finding of unknown cause usually associated with rheumatic disease. Only a few case reports of this entity are found in the literature, mostly describing the findings on conventional chest radiography, echocardiography, and angiography. To the best of our knowledge, this is the first case documented with multislice computed tomography. | 18,830,099 |
Craniofacial melorheostosis. | Melorheostosis is a rare benign disease of cortical bone most frequently presenting as peripheral hyperostosis with a characteristic "melting wax" appearance on conventional radiographs. The disease most frequently affects the appendicular skeleton and is seen only rarely in the craniofacial bones. We discuss a case of melorheostosis in the nasal cavity and skull base with an atypical radiographic appearance and suggest findings that may differentiate craniofacial melorheostosis from more common entities in this region. | 18,830,120 |
Isoquinoline alkaloids isolated from Corydalis yanhusuo and their binding affinities at the dopamine D1 receptor. | Bioactivity-guided fractionation of Corydalis yanhusuo has resulted in the isolation of eight known isoquinoline alkaloids - tetrahydropalmatine, isocorypalmine, stylopine, corydaline, columbamine, coptisin, 13-methylpalmatine, and dehydrocorybulbine. The tertiary alkaloids were further analyzed by chiral HPLC to determine the ratios of d-and l-isomers. The isolated compounds were screened for their binding affinities at the dopamine D(1) receptor. Isocorypalmine had the highest affinity (K(i) = 83 nM). The structure-affinity relationships of these alkaloids are discussed. | 18,830,156 |
Spontaneous rib fractures in a black woman with familial hypocalciuric hypercalcemia. | Familial hypocalciuric hypercalcemia (FHH) is a rare but important consideration in the differential diagnosis of hypercalcemia. FHH results from an autosomal dominantly inherited inactivating mutation of the calcium sensing receptor (CaSR) gene and is typically associated with a benign clinical course and normal bone mineral density. We describe the unusual case of a 57-year old African American woman with spontaneous rib fractures who was found to have FHH due to a novel set of polymorphisms of the CaSR gene. She also had hypertension, esophageal reflux disease treated with proton pump inhibitors, osteopenia by DEXA scanning, and a prior left ankle fracture in the absence of significant trauma. There was no suggestive family history and her only sibling had a normal serum calcium. The patient was evaluated extensively for potential causes of osteoporotic fractures. It is imperative to screen for FHH using 24-hour urinary calcium and creatinine excretion in subjects with hypercalcemia irrespective of ethnicity and a history of non-traumatic rib fractures. This approach may prevent unnecessary neck exploration for parathyroidectomy which is unwarranted in FHH. | 18,830,196 |
Rehabilitation of an artist after right-hemisphere stroke. | Traditionally, in both medicine and neuropsychology, symptoms are defined as significant deviations in a given parameter from a "physiological" norm largely based on statistical studies of large populations. Thus the goal of rehabilitation is to bring the patient's performance within the bounds of acceptable variation from the norm, and this is what defines a good outcome. Although this model seems reasonable for "average" patients, in the case of "exceptional" patients an "average" outcome may not be acceptable. The present study describes the symptoms and successful rehabilitation of a prominent Polish artist, who was referred for rehabilitation after a right hemisphere stroke, and whose chief subjective complaint was the loss of artistic vision. The patient (female, ambidextrous) suffered an RH stroke at the age of 61. In traditional rehabilitation many symptoms resolved and others were well compensated, but the patient continued to complain that she had a "hole" in her brain and could not paint. A special program of rehabilitation was designed for her, based on art therapy, but including many unique elements, using a microgenetic, "bottom-up" approach to energize creativity and bypass obstacles. Ultimately the patient was able to resume her artistic career, thanks to the heuristic, holistic approach to therapy. The case described here raises a number of theoretical questions about art, imagination, and creativity in the brain, and the goals of rehabilitation in the case of talented and gifted individuals. | 18,830,198 |
Squeezing and entanglement in a Bose-Einstein condensate. | Entanglement, a key feature of quantum mechanics, is a resource that allows the improvement of precision measurements beyond the conventional bound attainable by classical means. This results in the standard quantum limit, which is reached in today's best available sensors of various quantities such as time and position. Many of these sensors are interferometers in which the standard quantum limit can be overcome by using quantum-entangled states (in particular spin squeezed states) at the two input ports. Bose-Einstein condensates of ultracold atoms are considered good candidates to provide such states involving a large number of particles. Here we demonstrate spin squeezed states suitable for atomic interferometry by splitting a condensate into a few parts using a lattice potential. Site-resolved detection of the atoms allows the measurement of the atom number difference and relative phase, which are conjugate variables. The observed fluctuations imply entanglement between the particles, a resource that would allow a precision gain of 3.8 dB over the standard quantum limit for interferometric measurements. | 18,830,245 |
PD-1/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia/lymphoma patients. | Adult T-cell leukemia/lymphoma (ATLL) develops after infection with human T-cell leukemia virus-1 (HTLV-1) after a long latency period. The negative regulatory programmed death-1/programmed death-1 ligand 1 (PD-1/PD-L1) pathway has been implicated in the induction of cytotoxic T-lymphocyte (CTL) exhaustion during chronic viral infection along with tumor escape from host immunity. To determine whether the PD-1/PD-L1 pathway could be involved in the establishment of persistent HTLV-1 infections and immune evasion of ATLL cells in patients, we examined PD-1/PD-L1 expression on cells from 27 asymptomatic HTLV-1 carriers (ACs) and 27 ATLL patients in comparison with cells from 18 healthy donors. PD-1 expression on HTLV-1-specific CTLs from ACs and ATLL patients was dramatically elevated. In addition, PD-1 expression was significantly higher on CD8+ T cells along with cytomegalovirus (CMV)- and Epstein-Barr virus (EBV)-specific CTLs in ATLL patients compared with ACs and control individuals. Primary ATLL cells in 21.7% of ATLL patients expressed PD-L1, whereas elevated expression was not observed in cells from ACs. Finally, in functional studies, we observed that an anti-PD-L1 antagonistic antibody upregulated HTLV-1-specific CD8+T-cell response. These observations suggest that the PD-1/PD-L1 pathway plays a role in fostering persistent HTLV-1 infections, which may further ATLL development and facilitate immune evasion by ATLL cells. | 18,830,259 |
Functional characterization of IL-17F as a selective neutrophil attractant in psoriasis. | IL-17F is known to be involved in many inflammatory diseases, but its role in skin diseases has not been fully examined. Because IL-8 is involved in many skin diseases such as psoriasis, we investigated the production of IL-8 in normal human epidermal keratinocytes (NHEKs) stimulated by IL-17F, tumor necrosis factor-alpha (TNF-alpha), IL-17A, and control using real-time PCR and ELISA. The results showed that IL-17F induced production of IL-8 in NHEKs in a time-dependent manner. Interestingly, the amounts of IL-8 stimulated by IL-17F were much higher than those stimulated by TNF-alpha or IL-17A. Next, we confirmed that selective mitogen-activated protein kinase kinase inhibitors significantly inhibited IL-17F-induced IL-8 production. Moreover, mouse skin intradermally injected with IL-17F expressed high level of IL-8 mRNA and induced ERK1/2 phosphorylation. Histological examination of mouse skin that was injected with IL-17F revealed marked neutrophilia in dermis and the infiltration was significantly inhibited by anti-IL-8 antibody. Finally, IL-17F expression in skin biopsy samples from psoriasis patients were examined by western blotting and ELISA. IL-17F was upregulated in lesional psoriatic skin compared with nonlesional skin. These results indicate that IL-17F may be involved in psoriasis via, in part, the activation of ERK1/2 and the induction of IL-8 in keratinocytes. | 18,830,271 |
Quantitative comparison of quadratic covariance-based anomalous change detectors. | Simulations applied to hyperspectral imagery from the AVIRIS sensor are employed to quantitatively evaluate the performance of anomalous change detection algorithms. The evaluation methodology reflects the aim of these algorithms, which is to distinguish actual anomalous changes in a pair of images from the incidental differences that pervade the entire scene. By simulating both the anomalous changes and the pervasive differences, accurate and plentiful ground truth is made available, and statistical estimates of detection and false alarm rates can be made. Comparing the receiver operating characteristic (ROC) curves that encapsulate these rates provides a way to identify which algorithms work best under which conditions. | 18,830,282 |
Design and fabrication of a low-cost, multispectral imaging system. | This paper reports the design and construction of a low-cost, multispectral imaging system using a single, large format CCD and an array of 18 individual lenses coupled to individual spectral filters. The system allows the simultaneous acquisition of 18 subimages, each with potentially different optical information. The subimages are combined to create a composite image, highlighting the desired spectral information. Because all the subimages are acquired simultaneously, the composite image shows no motion artifact. Although the present configuration uses 17 narrow bandpass optical filters to obtain multispectral information from a scene, the system is designed to be a general purpose, multiaperture platform, easily reconfigured for other multiaperture imaging modes. | 18,830,286 |
Narrowband optical filters suitable for various applications in optical communications. | We propose three types of narrowband optical filters based on a Fox-Smith resonator. We demonstrate that by choosing the appropriate combination of coating materials on each prism facet, one can design either a high reflectance or a high transmittance optical filter, suitable for low bit rate optical communication applications with International Telecommunication Union-Telecommunication Standardization Sector (ITU-T) standards. We also show the possibility of designing an optical filter having a desirable finite reflectance/transmittance ratio with simultaneous peaks at ITU-T standard wavelengths. Such filters could be suitable for wavelength tuning applications. | 18,830,303 |
Propagation of a random electromagnetic beam through a misaligned optical system in turbulent atmosphere. | On the basis of the generalized diffraction integral formula for misaligned optical systems in the spatial domain, an analytical propagation expression for the elements of the cross-spectral density matrix of a random electromagnetic beam passing through a misaligned optical system in turbulent atmosphere is derived. Some analyses are illustrated by numerical examples relating to changes in the state of polarization of an electromagnetic Gaussian Schell-model beam propagating through such an optical system. It is shown that the misalignment has a significant influence on the intensity profile and the state of polarization of the beam, but the influence becomes smaller for the beam propagating in strong turbulent atmosphere. The method in this paper can be applied for sources that are either isotropic or anisotropic. It is shown that the isotropic sources and the anisotropic sources have different polarization properties on beam propagation. | 18,830,318 |
Evaluation and unification of some methods for estimating reflectance spectra from RGB images. | The problem of estimating spectral reflectances from the responses of a digital camera has received considerable attention recently. This problem can be cast as a regularized regression problem or as a statistical inversion problem. We discuss some previously suggested estimation methods based on critically undersampled RGB measurements and describe some relations between them. We concentrate mainly on those models that are using a priori information in the form of high-resolution measurements. We use the "kernel machine" framework in our evaluations and concentrate on the use of multiple illuminations and on the investigation of the performance of global and locally adapted estimation methods. We also introduce a nonlinear transformation of reflectance values to ensure that the estimated reflection spectra fulfill physically motivated boundary conditions. The reported experimental results are derived from measured and simulated camera responses from the Munsell Matte, NCS, and Pantone data sets. | 18,830,322 |
Scattering by a dense finite layer of infinite cylinders at oblique incidence. | This paper presents the scattering solution for a finite dense layer of cylinders irradiated by an arbitrarily polarized plane wave at a general incident direction. The theoretical formulation utilizes the effective field approach and quasi-crystalline approximation to derive the governing equations for the propagation constant and amplitudes of the effective waves. The finite layer thickness gives rise to effective waves propagating in both the forward and backward directions inside the dense medium. Formulas are developed for the far-field coherent and incoherent scattered intensities, as well as the extinction and scattering cross sections of the dense layer. The forward peak of the incoherent scattered intensity is shown to be shifted to the propagating direction of the effective waves. The influence of incident direction, layer thickness, and solid volume fraction on the scattering properties is illustrated by means of a numerical example. | 18,830,327 |
Velocity of heat dissipative solitons in optical fibers. | In the fiber fuse, a pulse of high temperature travels toward the input end of the fiber, where high-power laser light is launched into the fiber. At any point along the fiber, the soliton can be ignited. The fiber core is damaged in the process so that light cannot propagate beyond the hot spot. This phenomenon is an example of a dissipative soliton that can exist only in the presence of an external energy supply and internal loss. We analyze this phenomenon, derive an expression for the velocity of the soliton, and determine its width as functions of the physical parameters of the laser and the fiber material. | 18,830,343 |
Spectroscopy and femtosecond laser performance of Yb3+:YAlO3 crystal. | We report what we believe to be the first demonstration of cw and passively mode-locked Yb(3+):YAlO(3) (Yb:YAP) laser operation under diode pumping. Spectroscopic properties of a 0.6 at.%Yb(3+)-doped YAP single crystal were investigated. Output power up to 1.2 W with slope efficiency of 64.5% in the cw regime and 225 fs pulse duration with average power of 0.8 W from a mode-locked Yb:YAP laser were demonstrated. | 18,830,349 |
Quantum electrodynamics analysis of optical binding in counterpropagating beams and effect of particle size. | A general expression for optical binding energy between particles of any size, in counterpropagating beams with and without interference, is derived using quantum electrodynamics. The effect of particle size on the optically induced interparticle energy surface, which has been the subject of recent research, is explored. Significant changes in this surface when particle size approaches the wavelength of the optical field are revealed. Finally, optically induced particle arrays that may be fabricated with these potentials are briefly discussed. | 18,830,350 |
Electrically tunable Sagnac filter based on a photonic bandgap fiber with liquid crystal infused. | We demonstrate an electrically tunable Sagnac filter based on a photonic bandgap fiber that is realized by infusing liquid crystal into a solid-core air-hole photonic crystal fiber. The filter enables an electrical tuning with a range of about 26 nm for one single interference minimum in the transmission bandgap from 1330 to 1650 nm wavelength. The tuning efficiency is averaged to 0.53 nm/V. | 18,830,356 |
High-repetition-rate, 491 MHz, femtosecond fiber laser with low timing jitter. | We demonstrate a soliton fiber laser based on an anomalously dispersive erbium-doped fiber butt-coupled to a saturable absorber mirror for passive mode locking. The laser generates 180 fs pulses at a repetition rate of 491 MHz and exhibits a timing jitter as low as 20 fs over the frequency range 1 kHz-10 MHz. | 18,830,358 |
Biomimetic subwavelength antireflective gratings on GaAs. | We have developed a simple and scalable bottom-up approach for fabricating moth-eye antireflective coatings on GaAs substrates. Monolayer, non-close-packed silica colloidal crystals are created on crystalline GaAs wafers by a spin-coating-based single-layer reduction technique. These colloidal monolayers can be used as etching masks during a BCl(3) dry-etch process to generate subwavelength-structured antireflective gratings directly on GaAs substrates. The gratings exhibit excellent broadband antireflective properties, and the specular reflection matches with the theoretical prediction using a rigorous coupled-wave analysis model. These bioinspired antireflection coatings have important technological applications ranging from efficient solar cells to IR detectors. | 18,830,359 |
Prevention of decoherence by two femtosecond chirped pulse trains. | We study the vibrational energy relaxation (VER) and collisional dephasing as channels of coherence loss in a vibrational mode that is selectively excited using chirped pulse adiabatic passage in the Raman configuration. Based on the dressed state picture analysis we propose a method to reduce decoherence using femtosecond chirped pulse trains. When applied with a period close to the VER time, the pulse trains allow one to sustain high coherence in the selected vibrational mode. | 18,830,366 |
Time-resolved single-photon detection by femtosecond upconversion. | We demonstrate a time-resolved single-photon detection technique based on ultrafast sum-frequency generation, providing femtosecond measurement capability for single photons in photonic quantum information processing. Noncollinear broadband upconversion in periodically poled MgO-doped stoichiometric lithium tantalate with an ultrafast pump and detection with a Si single-photon counter enable efficient detection of IR photons and temporal resolution of ~150 fs. We utilize the timing resolution to map the generation efficiency profile along the propagation axis of a periodically poled KTiOPO(4) crystal, revealing its local grating quality with millimeter resolution. We also apply the technique to two-photon coincidence measurements and directly demonstrate time anticorrelation between coincident-frequency entangled photons that are parametrically generated under extended phase-matching conditions. | 18,830,370 |
Endocervicosis of the bladder: report of a case and review of the current literature. | An important variety of metaplastic lesions of the urinary bladder have been reported in the medical literature up to date. Among those of Müllerian origin, endocervicosis is the most infrequent. We report a 67 years old woman who presented with a history of left flank pain and dysuria for the past 2 months. Imaging studies revealed a solid mass in the posterior bladder wall protruding into the lumen. Transurethral resection of the lesion was performed. Both pathologic examination and immunohistochemistry confirmed the diagnosis of endocervicosis. The patient was monitored with 6 months interval follow up and remains disease free 12 months post surgery. | 18,830,389 |
Cost-effectiveness analysis for trigeminal neuralgia: Cyberknife vs microvascular decompression. | We present the preliminary results of a cost-effectiveness analysis of cyberknife radiosurgery (CKR) versus microvascular decompression (MVD) for patients with medically unresponsive trigeminal neuralgia. Direct healthcare costs from hospital's perspective attributable to CKR and MVD were collected. Pain level caused by trigeminal neuralgia was measured through the Barrow Neurological Institute pain intensity scoring criteria, at admission and after an average of 6 months follow-up. 20 patients for both arms were enrolled, for a total of 40 patients. The two procedures resulted equally effective at 6 month follow-up, with different resources consumption: CKR reducing hospital costs by an average of 34% per patient. The robustness of these results was confirmed in appropriate sensitivity analyses. CKR resulted to be a cost-saving alternative compared with the surgical intervention. | 18,830,392 |
Evolution of the aging brain transcriptome and synaptic regulation. | Alzheimer's disease and other neurodegenerative disorders of aging are characterized by clinical and pathological features that are relatively specific to humans. To obtain greater insight into how brain aging has evolved, we compared age-related gene expression changes in the cortex of humans, rhesus macaques, and mice on a genome-wide scale. A small subset of gene expression changes are conserved in all three species, including robust age-dependent upregulation of the neuroprotective gene apolipoprotein D (APOD) and downregulation of the synaptic cAMP signaling gene calcium/calmodulin-dependent protein kinase IV (CAMK4). However, analysis of gene ontology and cell type localization shows that humans and rhesus macaques have diverged from mice due to a dramatic increase in age-dependent repression of neuronal genes. Many of these age-regulated neuronal genes are associated with synaptic function. Notably, genes associated with GABA-ergic inhibitory function are robustly age-downregulated in humans but not in mice at the level of both mRNA and protein. Gene downregulation was not associated with overall neuronal or synaptic loss. Thus, repression of neuronal gene expression is a prominent and recently evolved feature of brain aging in humans and rhesus macaques that may alter neural networks and contribute to age-related cognitive changes. | 18,830,410 |
PTEN posttranslational inactivation and hyperactivation of the PI3K/Akt pathway sustain primary T cell leukemia viability. | Mutations in the phosphatase and tensin homolog (PTEN) gene leading to PTEN protein deletion and subsequent activation of the PI3K/Akt signaling pathway are common in cancer. Here we show that PTEN inactivation in human T cell acute lymphoblastic leukemia (T-ALL) cells is not always synonymous with PTEN gene lesions and diminished protein expression. Samples taken from patients with T-ALL at the time of diagnosis very frequently showed constitutive hyperactivation of the PI3K/Akt pathway. In contrast to immortalized cell lines, most primary T-ALL cells did not harbor PTEN gene alterations, displayed normal PTEN mRNA levels, and expressed higher PTEN protein levels than normal T cell precursors. However, PTEN overexpression was associated with decreased PTEN lipid phosphatase activity, resulting from casein kinase 2 (CK2) overexpression and hyperactivation. In addition, T-ALL cells had constitutively high levels of ROS, which can also downmodulate PTEN activity. Accordingly, both CK2 inhibitors and ROS scavengers restored PTEN activity and impaired PI3K/Akt signaling in T-ALL cells. Strikingly, inhibition of PI3K and/or CK2 promoted T-ALL cell death without affecting normal T cell precursors. Overall, our data indicate that T-ALL cells inactivate PTEN mostly in a nondeletional, posttranslational manner. Pharmacological manipulation of these mechanisms may open new avenues for T-ALL treatment. | 18,830,414 |
Deletion of GSK-3beta in mice leads to hypertrophic cardiomyopathy secondary to cardiomyoblast hyperproliferation. | Based on extensive preclinical data, glycogen synthase kinase-3 (GSK-3) has been proposed to be a viable drug target for a wide variety of disease states, ranging from diabetes to bipolar disorder. Since these new drugs, which will be more powerful GSK-3 inhibitors than lithium, may potentially be given to women of childbearing potential, and since it has controversially been suggested that lithium therapy might be linked to congenital cardiac defects, we asked whether GSK-3 family members are required for normal heart development in mice. We report that terminal cardiomyocyte differentiation was substantially blunted in Gsk3b(-/-) embryoid bodies. While GSK-3alpha-deficient mice were born without a cardiac phenotype, no live-born Gsk3b(-/-) pups were recovered. The Gsk3b(-/-) embryos had a double outlet RV, ventricular septal defects, and hypertrophic myopathy, with near obliteration of the ventricular cavities. The hypertrophic myopathy was caused by cardiomyocyte hyperproliferation without hypertrophy and was associated with increased expression and nuclear localization of three regulators of proliferation - GATA4, cyclin D1, and c-Myc. These studies, which we believe are the first in mammals to examine the role of GSK-3alpha and GSK-3beta in the heart using loss-of-function approaches, implicate GSK-3beta as a central regulator of embryonic cardiomyocyte proliferation and differentiation, as well as of outflow tract development. Although controversy over the teratogenic effects of lithium remains, our studies suggest that caution should be exercised in the use of newer, more potent drugs targeting GSK-3 in women of childbearing age. | 18,830,417 |
Dominican Children with HIV not Receiving Antiretrovirals: Massage Therapy Influences their Behavior and Development. | Forty-eight children (M age = 4.8 years) infected with HIV/AIDS and living in the Dominican Republic were randomly assigned to a massage therapy or a play session control group. The children in the massage therapy group received two weekly 20-min massages for 12 weeks; the children in the control group participated in a play session (coloring, playing with blocks) for the same duration and length as the massage therapy group. Overall, the children in the massage therapy group improved in self-help abilities and communication, suggesting that massage therapy may enhance daily functioning for children with HIV/AIDS. Moreover, the HIV infected children who were six or older also showed a decrease in internalizing behaviors; specifically depressive/anxious behaviors and negative thoughts were reduced. Additionally, baseline assessments revealed IQ equivalence below normal functioning for 70% of the HIV infected children and very high incidences of mood problems (depression, withdrawn) for 40% of the children and anxiety problems for 20% of the children, suggesting the need for better monitoring and alternative interventions in countries with limited resources to improve cognition and the mental health status of children infected with HIV/AIDS. | 18,830,444 |
Temperature-triggered gate opening for gas adsorption in microporous manganese formate. | Microporous manganese formate shows temperature-triggered gate opening for nitrogen and argon adsorption, which is not due to a structural change of the framework but due to dynamic opening of the pore aperture and/or sufficient kinetic energy of the adsorbates to overcome a diffusion barrier above a critical temperature. | 18,830,463 |
Total syntheses of (+/-)-montanin A and (+/-)-teuscorolide. | The first total syntheses of (+/-)-montanin A and (+/-)-teuscorolide have been achieved from an advanced precursor previously developed via a Diels-Alder strategy; in the synthetic sequence, the synthesis of montanin A was first accomplished in 8 steps, from which teuscorolide was readily achieved in 2 steps by using a novel furan oxidative cyclization-retro-cyclization process as a key operation. | 18,830,471 |
Lysine and arginine residues do not increase the helicity of alanine-rich peptide helices. | The helix-disfavoring, versus alanine, propagation values of lysine (0.8) and arginine (1.0) residues placed centrally in an (Ala)(9) unit have been measured by (13)C NMR. | 18,830,486 |
Auto-hydroxylation of FIH-1: an Fe(ii), alpha-ketoglutarate-dependent human hypoxia sensor. | HIF-asparaginyl hydroxylase (FIH-1) normally couples O(2)-activation to hydroxylation of Asn(803) on the alpha-subunit of the hypoxia-inducible factor (HIFalpha), a key step in pO(2) sensing; in the absence of HIFalpha, O(2)-activation becomes uncoupled, leading to self-hydroxylation at Trp(296) and a purple Fe(iii)-O-Trp chromophore-this alternative reactivity may affect human hypoxia sensing. | 18,830,487 |
Copper nanoparticles on hydrotalcite as a heterogeneous catalyst for oxidant-free dehydrogenation of alcohols. | We have developed a highly efficient heterogeneous catalytic system using hydrotalcite-supported Cu nanoparticles (Cu/HT) that can successfully promote the oxidant-free dehydrogenation of various alcohols under liquid-phase conditions. | 18,830,499 |
Gold-catalyzed efficient tandem assembly of terminal alkynes and arynes: synthesis of alkynylated biphenyl derivatives. | Gold catalysts have been found to catalyze the tandem assembly of arynes and terminal alkynes efficiently in the presence of CuI under mild reaction conditions to provide useful alkynylated biphenyl derivatives. | 18,830,501 |
Bromine-lithium exchange under non-cryogenic conditions: TMSCH(2)Li-LiDMAE promoted C-2 lithiation of 2,3-dibromopyridine. | The first C-2 selective bromine-lithium exchange in 2,3-dibromopyridine was performed at 0 degrees C in toluene using the TMSCH(2)Li-LiDMAE reagent. | 18,830,502 |
Home medicine chests and their relationship with self-medication in children and adolescents. | To investigate the contents of home medicine chests and their relationship with self-medication in children and adolescents in the towns of Limeira and Piracicaba, SP, Brazil. This is a descriptive population study based on a home survey of a simple random sample from both towns, comprising 705 households from census sectors selected by means of cluster sampling. age <or= 18 years; an obligatory interview with at least one guardian; inventory of medicines kept at home; and having taken at least one medication during the 15 days prior to the interview. The participants were split into two groups based on medication: self-medication (lay advice) and medical prescription. Tests of linear association were performed, in addition to a descriptive analysis of the variables and multiple logistic regression. A total of 3,619 medicines were found (mean = 5.1/household; 79.6% were pharmaceutical preparations). The rooms most commonly used to store medications were bedrooms (47.5%), kitchens (29.9%), and bathrooms (14.6%); 76.5% were in cardboard boxes and within easy reach of 142 children aged <or= 6 years. Taking the pharmaceutical preparations in isolation (n = 2,891), the most common were analgesics/antipyretics (26.8%) and systemic antibiotics (15.3%), and the self-medication group had significantly larger stocks of these medications (p < 0.01). Storing medications in the bathroom (odds ratios = 1.59) and legal guardians with <or= 4 years of primary education (odds ratios = 2.40) indicated greater risk of self-medication. Keeping medicines at home is a common practice, and it is important to implement campaigns to encourage rational use, reduced waste and safe storage of medicines. | 18,830,513 |
How frequently are physiological variables recorded in the emergency room in patients with obstructive pulmonary diseases and pneumonia? | To assess how frequently measurements of relevant physiological variables are made in patients presenting acutely to hospital with obstructive pulmonary diseases (OPD) and pneumonia. Patients admitted to three hospitals in western Norway with OPD (asthma or chronic obstructive pulmonary disease (COPD)) and/or pneumonia over a 75-day period were included in the study. The assessing physicians in the emergency room (ER) were asked to measure and record physiological variables according to normal practice. There were 338 patients (54% women), with an average age of 64 (SD 19) years. The initial diagnoses were OPD (176), pneumonia (103) and a combination of OPD and pneumonia (59). Heart rate and body temperature were recorded in almost all patients, whereas the recording of all other variables varied from 45% to 91%. Most variables were recorded more frequently in OPD than in pneumonia. The importance of recording respiratory rate, cutaneous oxygen saturation, and peak expiratory flow should be stressed in the training of physicians. | 18,830,520 |
Bilateral tarsometatarsal fracture-dislocations: a missed work-related injury. | Tarsometatarsal (Lisfranc) fracture-dislocation is an uncommon foot injury. Subtle injuries are more difficult to diagnose though they cause serious morbidity. Bilateral subtle tarsometatarsal injury has not been reported before. We report bilateral subtle tarsometatarsal dislocations that were caused by a work-related accident in a 25-year-old man. The injury was initially missed. Diagnosis was confirmed by computed tomography with curved reconstruction. Associated foot injuries are shown as a guide to the diagnosis. | 18,830,527 |
Adrenal cavernous haemangioma. | The adrenal gland is a rare location for haemangioma. Approximately 52 surgical cases have been reported in the literature. We report a huge non-functioning adrenal haemangioma presenting in a 50-year-old woman with flank pain. This was illustrated by computed tomography. It was surgically removed and diagnosed postoperatively as adrenal haemangioma. Although rare, adrenal haemangioma should be included in the differential diagnosis of adrenal neoplasms. The risks of haemorrhage, necrosis and thrombosis impose in the majority of cases surgical excision, particularly in tumours more than 3 cm in diameter. | 18,830,528 |
Arterial pressure changes during the Valsalva maneuver to predict fluid responsiveness in spontaneously breathing patients. | To evaluate whether arterial pressure response during a Valsalva maneuver could predict fluid responsiveness in spontaneously breathing patients. Prospective clinical study in a 17-bed multidisciplinary intensive care unit. Thirty patients without mechanical ventilation and equipped with a radial arterial catheter for whom the decision to give fluids was taken due to suspected hypovolemia. A 10-s Valsalva maneuver was performed before and after volume expansion (VE). Patients were classified as responders if stroke volume index (SVi) increased >/=15% after VE. Pulse pressure changes during the Valsalva maneuver (VPP) were calculated as the difference between maximal pulse pressure during phase 1 and minimal pulse pressure during phase 2 of the Valsalva maneuver divided by the mean of the two values and expressed as a percentage. Valsalva changes in systolic pressure (VSP) were calculated in similar way. SVi changes induced by VE was correlated with baseline values of VPP and VSP (r (2) = 0.71 and r (2) = 0.60; P < 0.0001, respectively), and with VE-induced changes in VPP and VSP (r (2) = 0.56 and r (2) = 0.44; P < 0.0001 and P < 0.001, respectively). A VPP value of 52% and VSP of 30% predicted fluid responsiveness with a sensitivity of 91% and 73% and a specificity of 95 and 90%, respectively. Arterial response during the Valsalva maneuver is a feasible tool for predicting fluid responsiveness in patients without mechanical ventilatory support. | 18,830,578 |
Inter-limb transfer of learned ankle movements. | Inter-limb learning transfer (ILT) between the upper-limbs has been well documented, but no corresponding study of the lower limbs has been done. We investigated ILT in the lower limbs of subjects who learned to move a cursor toward targets within 800 ms using ankle movements: plantar/dorsi-flexion and inversion/eversion. Twenty-two healthy right-dominant subjects were divided into two groups: half performed the tasks first using the right foot (group RL), and the other half performed it first with the left foot (group LR). Targets appeared on a computer screen at head-height while subjects were seated with one foot on a goniometric ankle platform. Subjects were required to move the cursor toward one of three randomly appearing targets under two conditions: (1) neutral or no visual motor rotation, and (2) with a 30 degrees visuo-motor rotation. Performance was quantified by computing the z-score for direction and position errors for each subject and ILT was assessed by comparing group performances for each foot. Results demonstrated that group LR but not group RL experienced significant ILT of directional as well as positional information in both tasks in a manner reflective of the distinctly different functional roles played by the upper and lower limbs. | 18,830,590 |
Expression of cGMP signaling elements in the Grueneberg ganglion. | The Grueneberg ganglion (GG) is a cluster of neurons localized to the vestibule of the anterior nasal cavity. Based on axonal projections to the olfactory bulb of the brain, as well as expression of olfactory receptors and the olfactory marker protein, it is considered a chemosensory subsystem. Recently, it was observed that in mice, GG neurons respond to cool ambient temperatures. In mammals, coolness-induced responses in highly specialized neuronal cells are supposed to rely on the ion channel TRPM8, whereas in thermosensory neurons of the nematode worm Caenorhabditis elegans, detection of environmental temperature is mainly mediated by cyclic guanosine monophosphate (cGMP) pathways, in which cGMP is generated by transmembrane guanylyl cyclases. To unravel the molecular mechanisms underlying coolness-induced responses in GG neurons, potential expression of TRPM8 in the murine GG was investigated; however, no evidence was found that this ion channel is present in the GG. By contrast, a substantial number of GG neurons was observed to express the transmembrane guanylyl cyclase subtype GC-G. In the nose, GC-G expression appears to be confined to the GG since it was not detectable in other nasal compartments. In the GG, coolness-stimulated responses are only observed in neurons characterized by the expression of the olfactory receptor V2r83. Interestingly, expression of GC-G in the GG was found in this V2r83-positive subpopulation but not in other GG neurons. In addition to GC-G, V2r83-positive GG cells also co-express the phosphodiesterase PDE2A. Thus, in summary, coolness-sensitive V2r83-expressing GG neurons are endowed with a cGMP cascade which might underlie thermosensitivity of these cells, similar to the cGMP pathway mediating thermosensation in neurons of C. elegans. | 18,830,617 |
Investigating differentiation mechanisms of the constituent cells of sex cord-stromal tumours of the ovary. | SOX-9, an essential factor for male sexual development, can be induced by prostaglandin D2 in a Sry-independent mechanism. Recent data suggest that the hedgehog pathway is involved in the differentiation of normal Sertoli and Leydig cells. The purpose of our study was to investigate the mechanisms involved in the differentiation of ovarian sex cord-stromal tumour (SCST) cells. Two Sertoli-Leydig cell tumours and two granulosa cell tumours with a minor Sertoli element were studied using immunohistochemistry on paraffin-embedded tissue sections. Sertoli cells expressed anti-Mullerian hormone (AMH), SOX-9, prostaglandin D synthase (Pgds) and bcl-2 (in four of four cases); sonic hedgehog (Shh) and p53 (in three of four cases) and androgen receptors (AR; in one of four cases). Ki-67 index ranged from 10% to 50%. Leydig cells expressed Shh and AR (two of two cases), while they showed no expression of p53, bcl-2 and 0% Ki-67 index. Granulosa cells expressed AMH, Pgds, Shh, estrogen receptors, progesterone receptors, AR and bcl-2 (in two of two cases) and p53 (in one of two cases). Ki-67 index was 10% and 40%, respectively. Further investigation is required to clarify the role of the molecules outlined above in the histogenesis of ovarian SCST, as Pgds-mediated SOX-9 upregulation could provide a reasonable explanation for the presence of testicular differentiation in ovarian SCST. | 18,830,622 |
Current practices in performing frozen sections for thyroid and parathyroid pathology. | In this review article, current trends in thyroid and parathyroid frozen sections are discussed. In Japan and other countries, the numbers of thyroid frozen sections have been dramatically decreasing over the past decade. The decline in the number of thyroid frozen sections has been attributed to two major factors: highly diagnostic preoperative fine needle aspiration for papillary carcinomas, the most frequent type of thyroid cancers, and the acknowledgment in the literature of the disadvantageous frozen sections for follicular tumors. Several authors have argued that the frozen section of thyroid nodules should be limited only to cases that have a preoperative cytology diagnosis as "atypical" or "suspicious". In contrast, frozen sections for parathyroid glands have been increasing in numbers. This increase is thought to be largely due to the high number of parathyroidectomies for secondary hyperplasia in dialysis patients. Frozen sections are usually performed to confirm the removal of parathyroid tissue for either cyropreservation or auto-transplantation. It is concluded that thyroid and parathyroid frozen section examination is restricted to selected situations. | 18,830,623 |
Increased expressions of cannabinoid receptor-1 and transient receptor potential vanilloid-1 in human prostate carcinoma. | Recently, functional cannabinoid receptor-1 (CB1) and vanilloid receptor-1 (TRPV1) have been described in human prostate and prostate cancer-derived cell lines where the activation of the receptors resulted in inhibition of cellular growth. We, however, lack the description of the expression of these molecules in human prostate cancer (PCC) and in benign prostate hyperplasia (BPH). Therefore, immunohistochemistry, Western blotting, and quantitative "real-time Q-PCR were performed to define the expressions of CB1 and TRPV1 in healthy and diseased prostate tissues. CB1 was identified in epithelial and smooth muscle cells types of the human prostate, whereas TRPV1 was exclusively localized to the mucosal cells. We also found that the expression of CB1 and TRPV1 (both at the protein and mRNA levels) were significantly up-regulated in PCC. However, while the increased expression of TRPV1 showed a proper correlation with increasing PCC tumor grades, such phenomenon was not observed with CB1. In addition, we also measured markedly elevated CB1 levels in BPH tissues whilst the expression of TRPV1 was not altered when compared to healthy control prostate. Our findings strongly argue for that (1) the CB1 and TRPV1 molecules as well as their ligands may indeed possess a promising future role in the treatment of PCC; (2) TRPV1 may also serve as a prognostic factor in PCC; and (3) CB1 may act as a potential target molecule in the therapeutic management of BPH. | 18,830,626 |
Cetuximab enhances the efficacy of bortezomib in squamous cell carcinoma cell lines. | Proteasome inhibition has been shown to be effective in multiple myeloma and solid tumor models. In this in vitro study, we investigated the antitumor effect of bortezomib (Velcade) in combination with cetuximab in squamous cell carcinoma cell lines (SCC). Dose-escalation studies were performed in five squamous cell carcinoma cell lines using bortezomib or cetuximab alone or in combination. Cell survival and growth inhibition were measured quantitatively using an MTT and LDH assay. Bortezomib alone showed a significant antiproliferative activity in all SCC cell lines (P < 0.042), and the activity was further significantly enhanced by the addition of cetuximab (P < 0.043). Our results indicate that cetuximab increases the cytotoxic activity of bortezomib in SCC cell lines. Combination therapy of SCC with bortezomib and cetuximab might be less toxic than conventional drug regimens used in the treatment of these tumors. | 18,830,627 |
Assessing the role of stress signalling via p38 MAP kinase in the premature senescence of ataxia telangiectasia and Werner syndrome fibroblasts. | The premature ageing ataxia telangiectasia (AT) and Werner syndromes (WS) are associated with accelerated cellular ageing. Young WS fibroblasts have an aged appearance and activated p38 MAP kinase, and treatment with the p38 inhibitor SB230580 extends their lifespan to within the normal range. SB203580 also extends the replicative lifespan of normal adult dermal fibroblasts, however, the effect is much reduced when compared to WS cells, suggesting that WS fibroblasts undergo a form of stress-induced premature senescence (SIPS). A small lifespan extension is seen in AT cells, which is not significant compared to normal fibroblasts, and the majority of young AT cells do not have an aged appearance and lack p38 activation, suggesting that the premature ageing does not result from SIPS. The lack of p38 activation is supported by the clinical manifestation, since AT is not associated with inflammatory disease, whereas WS individuals are predisposed to atherosclerosis, type II diabetes and osteoporosis, conditions known to be associated with p38 activation. | 18,830,681 |
Variability of the mitochondrial SSU rDNA of Nomuraea species and other entomopathogenic fungi from hypocreales. | Hypocrealean arthropod pathogenic fungi have profound impact on the regulation of agricultural and medical pests. However, until now the genetic and phylogenetic relationships among species have not been clarified, such studies could clarify host specificity relationships and define species boundaries. Our purpose was to compare the sequences of the mitochondrial SSU rDNA fragments from several mitosporic entomopathogenic Hypocreales to infer relationships among them and to evaluate the possibility to use these sequences as species diagnostic tool in addition to the more commonly studied sequences of nuclear SSU rDNA. The SSU mt-rDNA proved to be useful to help in differentiation of species inside several genera. Clusters obtained with Parsimony, Bayesian, and Maximum Likelihood analyses were congruent with a new classification of the Clavicipitaceae (Sung et al. Stud Mycol. 2007;57:5-59) in which the anamorphic genera Nomuraea and Metarhizium species remain in the Clavicipitaceae and Isaria species sequenced here are assigned to the family Cordycipitaceae. Mitochondrial genomic information indicates the same general pattern of relationships demonstrated by nuclear gene sequences. | 18,830,688 |
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