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101.
Defects in structures or functions of mitochondria, mainly involving the oxidative phosphorylation, mitochondrial biogenesis and other metabolic pathways have been shown to be associated with a wide spectrum of clinical phenotypes. The ubiquitous nature of mitochondria and their unique genetic features contribute to the clinical, biochemical and genetic heterogenecity of mitochondrial diseases. This article focuses on the recent advances in the field of mitochondrial disorders with respect to the consequences for an advanced clinical and genetic diagnostics. In addition, an overview on recently identified genetic defects and their pathogenic molecular mechanisms are given. 相似文献
102.
Gomes I Mathur SK Espenshade BM Mori Y Varga J Ackerman SJ 《The Journal of allergy and clinical immunology》2005,116(4):796-804
BACKGROUND: Eosinophils are frequently associated with tissue remodeling and fibrosis in allergic and other diseases and animal models. Their close physical proximity to fibroblasts at sites of tissue remodeling strongly implicates them in fibrogenesis, including subepithelial fibrosis and airway remodeling characteristic of asthma. OBJECTIVE: To identify the mediators and characterize the mechanisms underlying the fibrogenic activities of eosinophils. METHODS: A coculture system of blood eosinophils or eosinophil cell lines with normal fibroblasts was used to assess their ability to induce a fibrogenic fibroblast phenotype, including IL-6 secretion and mRNA expression, and induction of genes involved in extracellular matrix production and homeostasis. The mediators of these responses were identified by using transwell barrier cocultures, eosinophil-conditioned media, and cytokine-specific antibody neutralization. RESULTS: Eosinophil-fibroblast coculture induced potent fibroblast IL-6 secretion and mRNA expression, responses further enhanced by IL-5. The soluble nature of the eosinophil-derived mediators was demonstrated by using eosinophil-fibroblast coculture in the presence of permeable transwell barriers, and fibroblast culture in eosinophil-conditioned media, indicating that cell contact was not required. Induction of fibroblast IL-6 expression was accompanied by increased expression of fibronectin and the extracellular matrix regulatory genes plasminogen activator inhibitor 1 and tissue inhibitor of metalloproteinase 1. Antibody neutralization identified the principal eosinophil-derived mediator of fibroblast IL-6 expression as IL-1beta (>60%), with lesser contributions from IL-1alpha, IL-4, and TGF-beta (10% to 20%). CONCLUSION: Eosinophils express at least 2 potent mediators (IL-1beta and TGF-beta) that induce a fibrogenic fibroblast phenotype, strongly supporting a role for the eosinophil in the dysregulation of extracellular matrix homeostasis and consequent tissue remodeling and fibrosis in eosinophil-associated diseases. 相似文献
103.
Deshpande DA White TA Guedes AG Milla C Walseth TF Lund FE Kannan MS 《American journal of respiratory cell and molecular biology》2005,32(2):149-156
Cyclic ADP-ribose (cADPR) mobilizes calcium from intracellular stores and contributes to agonist-induced intracellular calcium elevation in airway smooth muscle (ASM). In this study we determined the functional role of CD38/cADPR signaling in the regulation of airway tone using CD38 deficient (cd38(-/-)) mice. The responsiveness to different doses of methacholine, as determined by changes in lung resistance and dynamic compliance, was significantly (P < or = 0.05) lower in cd38(-/-) mice compared with wild-type controls. To determine the mechanism responsible for the reduced responsiveness, we measured the intracellular calcium responses to contractile agonists in ASM cells. In ASM cells isolated from cd38(-/-) mice, the intracellular calcium responses to acetylcholine and endothelin-1 were significantly lower than in controls. Pretreatment of ASM cells with a cADPR antagonist resulted in attenuated intracellular calcium responses to endothelin-1 in cells isolated from wild-type mice, but not in those isolated from the cd38(-/-) mice. Very low cADPR levels and no detectable ADP-ribosyl cyclase activity were observed in lung tissue from cd38(-/-) mice, suggesting that CD38 is a critical source for cADPR synthesis. The results of the present study demonstrate that CD38/cADPR contributes to airway smooth muscle tone and responsiveness through its effects on agonist-induced elevation of intracellular calcium in ASM cells. 相似文献
104.
Study on the anatomical dimensions of the human sigmoid colon 总被引:4,自引:0,他引:4
Bhatnagar BN Sharma CL Gupta SN Mathur MM Reddy DC 《Clinical anatomy (New York, N.Y.)》2004,17(3):236-243
Although the sigmoid colon is commonly afflicted with disease, studies on its anatomical dimensions are scarce. It is suspected that dimensions of the sigmoid colon change with age. This study documents data on the anatomical measurements of the sigmoid colon in 70 Indian subjects (51 live and 19 cadavers). Seven parameters of sigmoid colon anatomy measured included length and width of the sigmoid colon and mesocolon at specific points. Three mesocolic indices (width to length ratios) were calculated. Comparisons of measurements in the live and cadaver subjects and in the two sexes were made. The relationship of change in parameters with age was assessed. Appropriate statistical methods were used and the differences were considered significant at P < or = 0.05. The study showed wide ranging variations in the values of various measured parameters of the sigmoid colon. Seven patterns of the shape of the sigmoid loop were identified. In the commonest pattern the sigmoid mesocolon was vertically longer than wide (dolichomesocolic), the sigmoid loop having its maximum convexity located just a little proximal to the apex. Patterns where the width of the mesocolon was greater than the vertical length (brachymesocolic) were also observed. The gender analysis showed that the sigmoid mesocolon of the female was brachymesocolic (wider than long), whereas that of the male was dolichomesocolic (longer than wide). This might explain the higher incidence of sigmoid volvulus in the male. This study also showed that the measurements of the sigmoid colon and its mesocolon do not change significantly within the age range of 16-60 years in the two sexes. Also noteworthy is the observation that in the cadaver the sigmoid colon shows considerable shrinkage, particularly of its mesocolon; consequently the data from cadaver subjects, though valuable for anthropometric use, have limitations when used for clinical applications. 相似文献
105.
Mathur SR Dahiya S Nayak A Bhatla N Singh MK 《Indian journal of pathology & microbiology》2004,47(3):333-335
We describe the clinicopathological and immunohistochemical findings in five cases of sclerosing stromal tumours of ovary and compare our findings with other reported cases of this uncommon tumour and with fibromas and thecomas which they may mimic. 相似文献
106.
107.
Genomics has contributed to a growing collection of gene-function and gene-disease annotations that can be exploited by informatics to study similarity between diseases. This can yield insight into disease etiology, reveal common pathophysiology and/or suggest treatment that can be appropriated from one disease to another. Estimating disease similarity solely on the basis of shared genes can be misleading as variable combinations of genes may be associated with similar diseases, especially for complex diseases. This deficiency can be potentially overcome by looking for common biological processes rather than only explicit gene matches between diseases. The use of semantic similarity between biological processes to estimate disease similarity could enhance the identification and characterization of disease similarity. We present functions to measure similarity between terms in an ontology, and between entities annotated with terms drawn from the ontology, based on both co-occurrence and information content. The similarity measure is shown to outperform other measures used to detect similarity. A manually curated dataset with known disease similarities was used as a benchmark to compare the estimation of disease similarity based on gene-based and Gene Ontology (GO) process-based comparisons. The detection of disease similarity based on semantic similarity between GO Processes (Recall=55%, Precision=60%) performed better than using exact matches between GO Processes (Recall=29%, Precision=58%) or gene overlap (Recall=88% and Precision=16%). The GO-Process based disease similarity scores on an external test set show statistically significant Pearson correlation (0.73) with numeric scores provided by medical residents. GO-Processes associated with similar diseases were found to be significantly regulated in gene expression microarray datasets of related diseases. 相似文献
108.
Swati Gupta Purva Mathur Dipesh Maskey Naveet Wig Sarman Singh 《AIDS research and therapy》2007,4(1):21-4
Background
Penicillium marneffei is a dimorphic fungus, endemic in South-east Asia. The fungus causes severe disease in immunocompromised patients such as AIDS. However, no case of immune restoration disease of Penicillium marneffei is reported in literature from a non-endemic area. 相似文献109.
Fine needle aspiration cytology (FNAC) enjoys popularity among clinicians worldwide, as a first line of investigation in all patients with lymphadenopathy and is preferred over biopsy because of its minimally invasive nature and cost-effectiveness. Although non-Hodgkin's lymphomas (NHL) are conventionally diagnosed and graded on biopsy specimens, it may be useful to be able to not only diagnose but also grade these cases on FNAC smears. The WHO and REAL classifications forming the basis of treatment in some centres rely on clinical features, immunocytochemistry and cytogenetics, which are beyond reach of most centres in the developing countries. This study therefore is aimed at diagnosing and grading NHLs on morphological parameters. The cytologic grading accuracy is compared with the histologic grades assigned according to the International Working Formulation (IWF) system which relies solely on morphological features, most important of which is cell size. Ninety five cases were retrieved over a 3 year period (May 2000 to April 2003). These were (i) cases where a cytological diagnosis of NHL or suspicious of NHL was made and corresponding histological sections available and (ii) cases where a diagnosis of NHL was made in histology and corresponding FNAC smears were available irrespective of the cytological diagnosis. The diagnostic accuracy of FNAC for NHLs was determined using histology as the gold standard. Cases were also graded on FNAC smears using a three tier grading system based upon cell size into low, intermediate and high grades. Cytologically assigned grades were correlated with the corresponding histological grades (IWF) to determine grading accuracy. An accurate diagnosis of NHL was thus possible in 67/95 (70.5%) cases. Overall accurate grading was seen in 65/95 (68%) cases using cytological criteria. Accurate cytologic grading was possible in 14/15 (93.33%) low grade, 11/18 (61.11%) intermediate and 40/62 (64.5%) high grade non Hodgkin's lymphomas. Kappa statistics revealed a very good agreement between cytological and histological grades for low grade NHL. The kappa scores for intermediate and high grade NHLs indicated moderate agreement. Using the two-tier system grading the kappa value for high grade lymphomas improved to 0.72, indicating good concordance. This study highlights the utility of FNAC as a morphological tool for diagnosing and grading NHLs in a significant number of cases. This modality may assist clinicians in management of cases of NHLs, especially in centres working within the constraints of limited availability or non availability of ancillary techniques. 相似文献
110.