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61.
62.
The X-linked Gy mutation is closely linked, but not allelic, to Hyp and is characterized by rickets, hypophosphatemia, decreased renal tubular maximum for phosphate (Pi) reabsorption (TmP) and a specific reduction in renal brush-border membrane (BBM) Na+-Pi cotransport. Gy mice, like their normal littermates, respond to a low-Pi diet with an increase in BBM Na+-Pi cotransport, but fail to show an adaptive increase in Tmp. Using an antibody raised against the NH2 terminal peptide of the rat renal-specific Na+-Pi cotransporter (NaPi-2) and a NaPi-2 cDNA probe, we examined the effect of the Gy mutation and low-Pi diet (0.03% Pi) on NaPi-2 protein and mRNA abundance. The reduction in BBM Na+-Pi cotransport in Gy mice (51 ± 5% of normal, P < 0.05) was associated with a decrease in NaPi-2 protein (46 ± 12% of normal, P < 0.05) and mRNA abundance (76 ± 5%, P < 0.05). The low-Pi diet elicited a two- to three-fold increase in Na+-Pi cotransport in both normal and Gy mice that was accompanied by a large increase in NaPi-2 protein (10.2-fold in normal and 16.9-fold in Gy mice) and a modest increase in NaPi-2 mRNA (1.3-fold in both mouse strains, P < 0.05). The present data demonstrate that (1) the renal defect in BBM Pi transport in Gy mice can be ascribed to a deficit in NaPi-2 protein and mRNA abundance, (2) both normal and Gy mice respond to low Pi with an adaptive increase in NaPi-2 protein that exceeds the increase in Na+-Pi cotransport activity and NaPi-2 mRNA, (3) the adaptive increase in NaPi-2 protein and mRNA are not sufficient for the overall increase in TmP following Pi restriction. Received: 27 October 1995 / Received after revision: 4 December 1995 / Accepted: 6 December 1995  相似文献   
63.
We studied, by immunohistochemical analysis, the expression of MUC1 and epithelial membrane antigen in 44 stage pT1 renal cell carcinomas (RCCs). Six patients had a metastatic evolution. The percentage of stained cells was determined for each tumor. All tumors and normal adjacent renal parenchyma were stained. In normal kidney, distal convoluted tubules and collecting ducts stained strongly with an apical distribution. In tumors, there was a significant statistical correlation of the MUC1 expression level with the nuclear grade and with tumor progression. High-grade tumors had more stained cells than did low-grade tumors. Metastatic tumors also were more stained than nonmetastatic lesions. By using the Kaplan-Meier method and the log-rank test, we observed that patients with fewer than 10% of stained cells had no metastatic evolution. In contrast, patients with 70% or more stained cells had significantly lower metastasis-free survival rates. We conclude that MUC1 is expressed in RCC and is associated with tumor progression in pT1 RCC.  相似文献   
64.
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors, initially described as molecular targets for synthetic compounds that induce peroxisome proliferation. PPARgamma is the best characterized of the PPARs. The heterodimer of PPARgamma with the retinoid X receptor (RXR) plays a crucial role in adipogenesis and insulin sensitization. The RXR/PPARgamma heterodimer furthermore has been reported to have important immunomodulatory activities and to affect cell proliferation/differentiation pathways in various malignancies. PPARgamma is activated by a number of naturally occurring fatty acid derivatives and by several synthetic compounds, including the thiazolidinediones and L-tyrosine-based insulin sensitizers. This review gives an overview of the pleiotropic functions of PPARgamma and discusses the wide-ranging medical implications that modulation of PPARgamma activity might have for various diseases, ranging from obesity and type 2 diabetes to cancer and inflammation.  相似文献   
65.
Blastic natural killer (NK) cell lymphoma (also termed CD4+CD56+ hematodermic neoplasm) is a recently described entity, with the first case reported in 1994. It was suggested initially that the disease originates from NK cells. Since 1994, single cases and a few small series have been published. In this review, data from the literature and a series of 30 cases from the French and Dutch study groups on cutaneous lymphomas are discussed. The major clinical, histopathologic, and phenotypic aspects of the disease and diagnostic criteria and data suggesting a plasmacytoid dendritic cell origin for the tumor cells are provided.  相似文献   
66.
The African pygmy mice, subgenus Nannomys, constitute the most speciose lineage of the genus Mus with 19 recognized species. Although morphologically very similar, they exhibit considerable chromosomal diversity which is here confirmed and extended by the G-banding analysis of 65 mice from West and South Africa. On the basis of their karyotype and distribution area, the specimens were assigned to at least five species. Extensive differentiation both within and between species was observed that involved almost exclusively Robertsonian translocations, 23 of which are newly described. Two of the rearrangements were sex chromosome-autosome translocations, associated in some cases with partial deletions of the X or Y chromosomes. Several authors have predicted that the highly deleterious effect of this rearrangement would be reduced if the sex and autosomal segments were insulated by a block of centromeric heterochromatin. The C-banding analyses performed showed that among the species carrying X-autosome translocations, one followed the expected pattern, while the other did not. In this case, functional isolation of the sex and autosome compartments must involve other repetitive sequences or genomic traits that require further molecular characterization. Such studies will provide insight into the causes and consequences of the high diversity of sex chromosome rearrangements in this subgenus.  相似文献   
67.
We report on three patients with Costello syndrome and isolated growth hormone (GH) deficiency treated with biosynthetic GH. To our knowledge, these are the only patients with Costello syndrome who have been successfully treated for GH deficiency. We review the pathophysiology of Costello syndrome and highlight the recent recommendations of tumor screening and cardiac surveillance in this population, of particular relevance to those receiving GH therapy.  相似文献   
68.
The prognostic value of early hepatitis C virus (HCV)-RNA load was evaluated among nonresponder patients to previous interferon (IFN) therapy treated with daily IFN and ribavirin. One hundred-six nonresponders (83 men), mean age 44.8 +/- 11 years, were treated with IFN-alpha 2b 3 MU/day for 24 weeks, followed by 3 MU x 3/week for 24 weeks plus ribavirin 1-1.2 g/day for 48 weeks. HCV RNA was quantified by Versant HCV RNA 3.0 assay (Bayer). The predictive values of the baseline and the change in viral load at week 1, 4, and 12 for sustained virological responses were analyzed using receiver operating characteristic (ROC) curves, as well as predictive values of >2 log(10) drop from baseline by weeks 1, 4, and 12 in combination with undetectable HCV RNA for sustained virological response. Thirty-two patients (30.2%) were sustained virological responders. The highest area under the curve was obtained at week 4. The unquantifiable HCV RNA level, in combination with at least a 2 log(10) drop in viral load by week 4 and week 12, had a negative predictive value of 96% and 97%, respectively. Nonresponse can be predicted as early as week 4 or week 12 in nonresponders treated with daily IFN and ribavirin.  相似文献   
69.
Gene transfer approaches using viruses such human adenovirus (HAdV) may provide an alternative treatment for diseases involving hematopoietic cells. Better understanding of the cellular mechanisms by which the HAdV introduces DNA into these cells should help in vector design. We examined HAdV intracellular delivery in several cell lines including B and T lymphocytes. We demonstrated that HAdV resistance in most B lymphocytes is the result of moderate HAdV uptake. In contrast, high levels of coxsackie and HAdV receptor (hCAR) are expressed on the surface of HSB2 (T cells), allowing efficient binding and uptake but no transgene expression, probably because of deficient endosomolysis and subsequent exocytose. This work demonstrates the existence of hCAR-dependent and -independent endocytic route in hematopoietic cells. Moreover, it precises the intracellular barriers to be overcome by HAdV in such cells to be infectious and gives previous information's to design new vectors for gene transfer.  相似文献   
70.
While chromosome 1p36 deletion syndrome is one of the most common terminal subtelomeric microdeletion syndrome, 1p36 microduplications are rare events. Polymicrogyria (PMG) is a brain malformation phenotype frequently present in patients with 1p36 monosomy. The gene whose haploinsufficiency could cause this phenotype remains to be identified. We used high-resolution arrayCGH in patients with various forms of PMG in order to identify chromosomal variants associated to the malformation and characterized the genes included in these regions in vitro and in vivo. We identified the smallest case of 1p36 duplication reported to date in a patient presenting intellectual disability, microcephaly, epilepsy, and perisylvian polymicrogyria. The duplicated segment is intrachromosomal, duplicated in mirror and contains two genes: enolase 1 (ENO1) and RERE, both disrupted by the rearrangement. Gene expression analysis performed using the patient cells revealed a reduced expression, mimicking haploinsufficiency. We performed in situ hybridization to describe the developmental expression profile of the two genes in mouse development. In addition, we used in utero electroporation of shRNAs to show that Eno1 inactivation in the rat causes a brain development defect. These experiments allowed us to define the ENO1 gene as the most likely candidate to contribute to the brain malformation phenotype of the studied patient and consequently a candidate to contribute to the malformations of the cerebral cortex observed in patients with 1p36 monosomy.Subject terms: Gene regulation, Genetics research  相似文献   
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