Brain abnormalities in Williams syndrome (WS) have been consistently reported, despite few studies have devoted attention to connectivity between different brain regions in WS. In this study, we evaluated corpus callosum (CC) morphometry: bending angle, length, thickness and curvature of CC using a new shape analysis method in a group of 17 individuals with WS matched with a typically developing group. We used this multimethod approach because we hypothesized that neurodevelopmental abnormalities might result in both volume changes and structure deformation. Overall, we found reduced absolute CC cross-sectional area and volume in WS (mean CC and subsections). In parallel, we observed group differences regarding CC shape and thickness. Specifically, CC of WS is morphologically different, characterized by a larger bending angle and being more curved in the posterior part. Moreover, although CC in WS is shorter, a larger relative thickness of CC was found in all callosal sections. Finally, groups differed regarding the association between CC measures, age, white matter volume and cognitive performance. In conclusions, abnormal patterns of CC morphology and shape may be implicated in WS cognitive and behavioural phenotype. 相似文献
Aim of the present study was to investigate whether 1,25(OH)(2)D(3) (Vitamin D3) modulates T lymphocyte functions in patients transplanted for hepatitis C virus-related cirrhosis.
Methods
Sixteen patients and ten healthy subjects were investigated. T lymphocytes were activated in vitro in the presence or absence of Vitamin D3 and then the proliferative response and IFN-γ and TNF-α production were assessed.
Results
Vitamin D3 potently reduced T-lymphocyte proliferation in a dose-related fashion. Similarly, FACS analysis and ELISA testing demonstrated that Vitamin D3 significantly decreased the response frequency and the response intensity of IFN-γ and TNF-α production in the whole CD3-positive T lymphocyte population as well as in “naive” CD4+ CD45RA+ and “memory” CD4+ CD45RO+ T lymphocyte subsets. The inhibitory effect of Vitamin D3 on T-cell proliferation and cytokine production was not different between patients and controls. No toxic effects were exerted by Vitamin D3 even at the higher concentration used (10 nM). Finally, no statistically significant correlation was found between 25(OH)D serum levels and the proliferative response or cytokine production of T lymphocytes from transplanted patients.
Conclusions
This study demonstrates that in patients transplanted for hepatitis C virus-related cirrhosis Vitamin D3 modulates T lymphocyte activation, and provides a rationale for the evaluation of this compound as an immunosuppressive agent in liver-transplanted patients. 相似文献
This study examined the test–retest reliability, consensual, convergent and divergent validities, sensitivity, specificity, positive and negative predictive values, and accuracy of the Portuguese version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL). Eighty-nine children/adolescents (65 psychiatric outpatients and 24 healthy controls) were interviewed with K-SADS-PL and completed measures of depressive and anxiety symptoms. The child’s parent/caretaker completed the Child Behavior Checklist. Good to excellent values were obtained for test–retest reliability and consensual validity. For the convergent validity, moderate correlations between the K-SADS-PL and the corresponding self-report measures were observed. Divergent validity was acceptable for the K-SADS-PL diagnoses. The lowest values of sensitivity, specificity, and accuracy of the K-SADS-PL were 88, 88, and 91, respectively. The Portuguese version of K-SADS-PL proved to be a valid and reliable assessment instrument for children and adolescents, and was sensitive, specific and accurate when diagnosing mood, anxiety, adjustment, and attention-deficit/hyperactivity disorders.
Human mesenchymal stromal (stem) cells (hMSCs) isolated from adult bone marrow (BM-hMSCs) as well as amnion (AM-hMSCs) and chorion (CM-hMSCs) term placenta leaves were studied by transmission electron microscopy (TEM) to investigate their ultrastructural basic phenotype. At flow cytometry, the isolated cells showed a homogeneous expression of markers commonly used to identify hMSCs, i.e., CD105, CD44, CD90, CD166, HLA-ABC positivities, and CD45, AC133, and HLA-DR negativities. However, TEM revealed subtle yet significant differences. BM-hMSCs had mesenchymal features with dilated cisternae of rough endoplasmic reticulum (rER) and peripheral collections of multiloculated clear blisters; this latter finding mostly representing complex foldings of the plasma membrane could be revelatory of the in situ cell arrangement in the niche microenvironment. Unlike BM-hMSCs, CM-hMSCs were more primitive and metabolically quiescent, their major features being the presence of rER stacks and large peripheral collections of unbound glycogen. AM-hMSCs showed a hybrid epithelial-mesenchymal ultrastructural phenotype; epithelial characters included non-intestinal-type surface microvilli, intracytoplasmic lumina lined with microvilli, and intercellular junctions; mesenchymal features included rER profiles, lipid droplets, and well-developed foci of contractile filaments with dense bodies. These features are consistent with the view that AM-hMSCs have a pluripotent potential. In conclusion, this study documents that ultrastructural differences exist among phenotypically similar hMSCs derived from human bone marrow and term placenta leaves; such differences could be revelatory of the hMSCs in vitro differentiation potential and may provide useful clues to attempt their in situ identification. 相似文献
The presence of autoantibodies specific for nucleic acid-associated antigens is the hallmark of systemic lupus erythematosus (SLE). We have recently developed a specific inhibitor of TLR7 and TLR9, called immunoregulatory sequence (IRS) 954, and showed that it inhibits the induction of IFN-alpha by human plasmacytoid dendritic cells in response to DNA and RNA viruses and isolated immune complexes from lupus patients. In this study, we show that IRS 954 can prevent progression of disease when injected in the lupus prone (NZBxNZW)F1 mice. Following treatment, we observed a significant reduction of serum levels of nucleic acid-specific autoantibodies as well as decreased proteinuria, reduced glomerulonephritis, end-organ damage and increased survival. These data demonstrate that in addition to its ability to block IFN-alpha, IRS 954 can reduce symptoms in a lupus model and thus represents a promising therapeutic agent for the treatment of SLE. 相似文献
Oxaliplatin (OXA) is a platinum compound widely used in the treatment of some solid tumors, especially colorectal cancer. Despite its usefulness, oxaliplatin-associated neurotoxicity represents the main dose-limiting factor of this drug, and until now, there is no suitable treatment. Chemotherapy with oxaliplatin also increases the rate of developing hepatic damages with inflammatory activity, termed chemotherapy-associated steatohepatitis (CASH). In the present study, we aimed to compare the effects of a series of antioxidant compounds on simultaneous development of oxaliplatin-induced hepato- and neurotoxicity in mice. Mice BALB/c were treated with oxaliplatin for 6 weeks, 10 mg/kg, intraperitoneally, resulting in mechanical allodynia and hepatic steatosis. We administered the following antioxidant compounds—rutin (RT) (20 mg/kg), resveratrol (RVS) (100 mg/kg), quercetin (QT) (20 mg/kg), and quercetin nanoemulsion (NQT) (20 mg/kg)—daily by gavage to BALB/c, and N-acetylcysteine (NAC) was used as positive control. Treatments with RSV, RUT, or NQT were able to prevent mechanical allodynia when compared to the OXA group, and this effect was associated with decreased c-Fos immunopositivity in the lumbar spinal cord. Regarding the effects on steatohepatitis, RVS, QT, and NQT almost completely reversed the mean liver weight increase induced by OXA. In accordance with these previous data, histological evaluation indicated attenuation of all features of hepatic steatosis evaluated in RSV, RUT, QT, and NQT groups. These compounds were able to reduce the immunopositivity for the apoptosis marker caspase-3. On the other hand, only QT and NQT treatments were able to reduce neutrophil migration measured by myeloperoxidase (MPO) activity. These results suggest that the compounds tested, RSV, RUT, QT, and NQT, would be useful for the clinical treatment of neuro- and hepatoxicity induced by oxaliplatin. 相似文献
This article provides a summary of the results of a recent survey in the pharmaceutical and device industry on the current practice and common issues in the identification and analysis of subgroups. The survey was part of a cross-industry effort sponsored by the Quantitative Sciences in the Pharmaceutical Industry (QSPI) for two purposes: (1) to identify general practices in how statistical subgroup analyses are planned and conducted in clinical trials and (2) collect information on similarities and differences across the prespecified types of subgroup analyses in terms of most common challenges, methodologies, and other characteristics. The survey results help integrate good practices and create a unifying framework for subgroup analyses in industry encompassing those in discovery/early phases directed to biomarkers identification and those at later stages for exploratory, confirmatory, or post hoc evaluations. Results from this survey identify the number one challenge to be the lack of power related to the sample size and number of subgroups tested. The findings further highlight an unmet need for intensified educational efforts focused on sharing statistical methodologies, experiences, and knowledge on the most appropriate approaches for identifying and analyzing subgroups. The scientific debate among industry, regulators and academia should continue to find solutions to unresolved challenges and perceived difficulties of subgroup analyses in clinical trials. 相似文献