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81.
WT1 is a key regulator of podocyte function: reduced expression levels cause crescentic glomerulonephritis and mesangial sclerosis 总被引:15,自引:0,他引:15
Guo JK Menke AL Gubler MC Clarke AR Harrison D Hammes A Hastie ND Schedl A 《Human molecular genetics》2002,11(6):651-659
Glomerular disease is one of the most common causes of end-stage renal failure. Increasing evidence suggests that these glomerulopathies are frequently caused by primary lesions in the renal podocytes. One of the major consequences of podocyte lesions is the accumulation of mesangial matrix in the glomerular basement membrane, a process called glomerulosclerosis. Mesangial sclerosis is one of the most consistent findings in Denys-Drash patients and can be caused by dominant mutations in the Wilms' tumor 1 gene (WT1). The underlying mechanism, however, is poorly understood. WT1 is expressed in the podocytes throughout life, but its function in this cell type is unknown. Combining Wt1-knockout and inducible yeast artificial chromosome transgenic mouse models, we demonstrate that reduced expression levels of WT1 result in either crescentic glomerulonephritis or mesangial sclerosis depending on the gene dosage. Strikingly, the two podocyte-specific genes nphs1 and podocalyxin are dramatically downregulated in mice with decreased levels of Wt1, suggesting that these two genes act downstream of Wt1. Taken together, our data provide genetic evidence that reduced levels of Wt1 are responsible for the pathogenesis of two distinct renal diseases and offer a molecular explanation for the increased occurrence of glomerulosclerosis in patients with WAGR syndrome. 相似文献
82.
Müller AM Hermanns MI Skrzynski C Nesslinger M Müller KM Kirkpatrick CJ 《Experimental and molecular pathology》2002,72(3):221-229
EC culture models are essential to study pathological alterations of endothelial cells (ECs) in pulmonary vascular diseases under standardized conditions. Nevertheless, little is known about the spectrum of alterations of vessel-specific endothelial phenotypes in monolayer cultures. For the comparative study of endothelial markers in vivo and in vitro we investigated immunohistochemically the expression of PECAM-1, vWf, and CD34 by pulmonary ECs in vivo and in stimulated/unstimulated human umbilical vein endothelial cells (HU-VEC) and human pulmonary microvascular endothelial cells (HPMEC). In vivo, vessel type-specific expression patterns were found for vWf and CD34, while PECAM-1 was homogeneously and strongly expressed. While all HUVEC showed a marked vWf staining, about two-thirds of HPMEC exhibited a strong and the rest a moderate vWf staining. In both in vitro models all ECs were clearly PECAM-1-positive. However, only about 20% of the HUVEC and HPMEC were CD34-positive. Our results demonstrate the reduced expression of vessel type-specific endothelial phenotypes by endothelial monolayer cultures, stressing the need to improve culture conditions as well as develop cocultures and three-dimensional culture models. Moreover, the need for endothelial markers specific for single microvascular type ECs becomes obvious in order to establish cultures consisting of only one microvascular ECs subpopulation. 相似文献
83.
Decrease and gain of gene expression are equally discriminatory markers for prostate carcinoma: a gene expression analysis on total and microdissected prostate tissue 总被引:8,自引:0,他引:8
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84.
Annette J Schlueter Arthur M Krieg Peter De Vries Xiang Li 《Journal of interferon & cytokine research》2002,22(7):799-806
Interferon-alpha (IFN-alpha) is the primary regulator of transient Ly-6C expression on T cells. B cells, which do not express Ly-6C in the resting state, have been reported to express Ly-6C following exposure to proinflammatory stimuli. This study examined the factors controlling Ly-6C expression on B cells and the kinetics of Ly-6C expression in the presence of these factors. In vivo studies demonstrated that proinflammatory (Th1) cytokines transiently upregulate B cell Ly-6C expression. In vitro studies identified Th1 cytokines, particularly IFN-alpha and IFN-gamma, as the principal cytokines responsible for this induction. Polyclonal B cell activators (anti-IgM and recombinant CD40 ligand trimer) showed minimal ability to independently induce Ly-6C expression on B cells but did enhance the ability of IFNs to induce expression. Th2 cytokine environments did not result in B cell Ly-6C expression, and interleukin-4 (IL-4) actually antagonized the IFN-driven induction of Ly-6C. Ly6.1 strains of mice consistently demonstrated a greater ability to express Ly-6C on B cells than did Ly-6.2 strains. Together, these studies demonstrate the ability of Th1 but not Th2 cytokine environments to transiently induce the expression of Ly-6C on B cells and provide additional evidence for differences in the regulation of Ly-6C expression in Ly6.1 and Ly6.2 strains. 相似文献
85.
Cindy Johnston Stephan Eliez Jennifer Dyer‐Friedman David Hessl Bronwyn Glaser Christine Blasey Annette Taylor Allan Reiss 《American journal of medical genetics. Part A》2001,103(4):314-319
There have been contradictory findings in the fragile X (fraX) literature about possible neurocognitive and psychological symptoms due to the fraX premutation (pM). The purpose of the present study was to investigate the relationship between CGG repeat length and neurobehavioral functioning in carriers of the fraX pM. Eighty‐five female carriers of the pM with allele sizes ranging from 59–166 were administered a comprehensive IQ test (WAIS‐III) and completed a questionnaire designed to measure psychopathology (Symptom Checklist (SCL)‐90‐R). No relationship between allele size and cognition was identified. A significant negative relationship between allele size and age was found, as well as a positive relationship between allele size and depression. Follow‐up analyses separating small and large allele sizes (below and above 100 CGG repeats) indicated that individuals with larger allele sizes scored significantly higher on the Interpersonal Sensitivity and Depression subscales of the SCL‐90‐R. Despite the limitation of few individuals with high CGG repeat lengths, our findings suggest that females with larger premutated alleles (≥ 100 repeats) display some clinical manifestations of fraX syndrome. © 2001 Wiley‐Liss, Inc. 相似文献
86.
CD34(+) fibrocytes in normal cervical stroma,cervical intraepithelial neoplasia III,and invasive squamous cell carcinoma of the cervix uteri 总被引:3,自引:0,他引:3
Barth PJ Ramaswamy A Moll R 《Virchows Archiv : an international journal of pathology》2002,441(6):564-568
CD34(+) fibrocytes are widely distributed in normal connective tissues but have been reported to be absent within the stroma associated with invasive carcinomas. In the present study we investigated the presence and distribution of CD34(+) fibrocytes and alpha-smooth muscle actin (alpha-SMA) positive myofibroblasts in cervical intraepithelial neoplasia III (CIN III; n=8), invasive carcinoma of the cervix ( n=18) and adjacent normal cervical stroma. Normal cervical stroma and the stroma adjacent to CIN III disclosed a dense network of CD34(+) fibrocytes, whereas the stroma of invasive carcinoma was virtually free of this cell population. Early stromal invasion by squamous carcinoma was characterized by a focal loss of CD34(+) fibrocytes. alpha-SMA-positive myofibroblasts were not seen in the normal cervical stroma but occurred in six of eight cases of CIN III adjacent to the atypical epithelium. The stroma of invasive carcinoma was made up of large amounts of haphazardly arranged alpha-SMA-positive myofibroblasts. In the setting of the present study, a loss of CD34(+) fibrocytes was specific for stromal alterations associated with invasive carcinoma and proved to be a sensitive tool in detecting small foci of stromal invasion. Therefore, detection of a loss of CD34(+) fibrocytes may constitute an adjunctive tool in detecting (1) early stromal invasion and (2) invasive carcinoma in small biopsy specimens. Moreover, the present study shows that CD34(+) fibrocytes and myofibroblasts play an important role in stromal remodeling associated with invasive squamous cell carcinoma of the cervix. 相似文献
87.
Annette Hus-Citharel Olivier Levillain François Morel 《Pflügers Archiv : European journal of physiology》1995,429(4):485-493
The distribution of arginine synthase and arginase activities along the successive nephron segments ofMeriones kidney was measured in vitro with single tubule enzymatic microtechniques making use of eitherl-[ureido-14C] Citrulline (0.108 mM) orl-[guanidion-14C]arginine (0.2 mM) as the respective substrates. Arginase activity (fmol urea formed per min per mm of tubule) was very low (5–25 fmol.min–1.mm–1) in most nephron segments including the early portions of proximal convoluted tubules (early PCT). It increased progressively after 3 mm of the PCT to reach a value of 200 fmol.min–1.mm–1 in the cortical portion of the straight proximal tubule (CPST), with a further increase, along the pars recta, of up to 250 fmol.min–1.mm–1 in the outer medullary portion (OSPST). In addition, arginase activity in OSPST and the adjacent descending thin limb (DTL) was higher in juxtamedullary nephrons (JN) than in the corresponding portions of superficial nephrons (SN). Arginine synthase activity (fmol arginine formed per mm of tubule per min) was present in proximal tubules exclusively, with a gradient decreasing along the PCT (about 600 fmol.min–1.mm–1 in the 1st mm, 65 fmol.min–1.mm–1 in CPST and 30 fmol. min–1. mm–1 in OSPST). It has been checked that CPST and OSPST (where the two enzyme systems are present) are able to convert citrulline directly into urea with a yield of 65%. It is suggested that: (1) in early PCT cells, arginine synthase activity permits the conversion of the reabsorbed citrulline into arginine (which then diffuses towards blood vessels); and (2) in pars recta cells, arginase activity results in a net entry of arginine across the basolateral membranes and in a net exit of the formed urea into the tubular fluid, if the permeability to urea of luminal membranes is greater than that of basolateral membranes. Such a mechanism of urea secretion might contribute to the maintenance of urea recycling in the medulla and, thereby, participate in the process of concentrating the urine. 相似文献
88.
Roland Berger Josette Hillion Daniel Janvier Zhu Chen Annette Bussel 《Cancer Genetics and Cytogenetics》1993,70(2):125-126
A t(8;21)(q22;q22) without blood and bone marrow invasion by immature myeloid precursor cells occurred in a patient previously treated for polycythemia vera. The presence of a molecular rearrangement confirmed that the chromosomal abnormality was identical to that observed in acute leukemia with t(8;21). This case shows that the translocation, t(8;21), may occur in myelodysplasia and suggests that it can precede the appearance of overt leukemia. 相似文献
89.
Use of type 1 /type 2 chimeric polioviruses to study determinants of poliovirus type 1 neurovirulence in a mouse model 总被引:13,自引:0,他引:13
Annette Martin Danile Benichou Thrse Couderc James M. Hogle Czeslaw Wychowski Sylvie Van Der Werf Marc Girard 《Virology》1991,180(2):648-658
We previously described the characteristics of a type 1/type 2 (PV-1/PV-2) chimeric poliovirus, v510, which contains the six amino acids specific for PV-2 in the B-C loop of VP1. This virus was found to be mouse-adapted, as PV-2 and in contrast with PV-1. Determinants of host range were studied in detail and are reported here. PV-1/PV-2 chimeras containing partial PV-1----PV-2 substitutions in the B-C loop of VP1 were obtained by making use of a mutagenesis cartridge on PV-1 cDNA. Analysis of mouse neurovirulence of these chimeras, when correlated with the three-dimensional structure of the v510 capsid, revealed that PV-2 residues important for mouse tropism are those which determine the particular conformation of the B-C loop of VP1 in v510. The mutation of the adenine residue at position 480 of the 5' noncoding region into a guanine residue has been shown to be an important determinant of PV-1 attenuation in monkeys. We show that introduction of this mutation in the v510 genome results in a virus which is partially attenuated for mice. This suggests that analysis of genomic determinants important for PV-1 neurovirulence could be carried out in a mouse model by making use of a mouse-adapted PV-1/PV-2 chimera. 相似文献
90.
Childhood peer rejection and aggression as predictors of adolescent girls' externalizing and health risk behaviors: a 6-year longitudinal study 总被引:5,自引:0,他引:5
This 6-year longitudinal study examined girls' peer-nominated social preference and aggression in childhood as predictors of self- and parent-reported externalizing symptoms, substance use (i.e. cigarette, alcohol, and marijuana use), and sexual risk behavior in adolescence. Participants were 148 girls from diverse ethnic backgrounds, who were initially assessed in Grades 4-6 and again in Grades 10-12. Results supported a moderator model, indicating that social preference changed the nature of the association between childhood aggression and adolescent outcomes. When accompanied by peer rejection, aggressive behavior was moderately stable over time and significantly associated with adolescent girls' substance use and sexual risk behavior. However, under conditions of peer acceptance, no significant association between childhood aggression and adolescent outcomes emerged. 相似文献