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941.
George Capone Mary Stephens Stephanie Santoro Brian Chicoine Peter Bulova Moya Peterson Joan Jasien Anna Jo Smith Down Syndrome Medical Interest Group Adult Health Workgroup 《American journal of medical genetics. Part A》2020,182(7):1832-1845
Adults with Down syndrome (DS) represent a unique population who are in need of clinical guidelines to address their medical care. Many of these conditions are of public health importance with the potential to develop screening recommendations to improve clinical care for this population. Our workgroup previously identified and prioritized co‐occurring medical conditions in adults with DS. In this study, we again performed detailed literature searches on an additional six medical conditions of clinical importance. A series of key questions (KQ) were formulated a priori to guide the literature search strategy. Our KQs focused on disease prevalence, severity, risk‐factors, methodologies for screening/evaluation, impact on morbidity, and potential costs/benefits. The available evidence was extracted, evaluated and graded on quality. The number of participants and the design of clinical studies varied by condition and were often inadequate for answering most of the KQ. Based upon our review, we provide a summary of the findings on hip dysplasia, menopause, acquired cardiac valve disease, type 2 diabetes mellitus, hematologic disorders, and dysphagia. Minimal evidence demonstrates significant gaps in our clinical knowledge that compromises clinical decision‐making and management of these medically complex individuals. The creation of evidence‐based clinical guidance for this population will not be possible until these gaps are addressed. 相似文献
942.
c-Fos-dependent induction of the small ras-related GTPase Rab11a in skin carcinogenesis 总被引:1,自引:0,他引:1 下载免费PDF全文
Gebhardt C Breitenbach U Richter KH Fürstenberger G Mauch C Angel P Hess J 《The American journal of pathology》2005,167(1):243-253
Malignant transformation of mouse skin by tumor promoters and chemical carcinogens, such as the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), is a multistage process leading to the formation of squamous cell carcinomas. It has been shown that mice lacking the AP-1 family member c-Fos exhibit an impaired transition from benign to malignant skin tumors. Here, we demonstrate enhanced expression of the small Ras-related GTPase Rab11a after short-term TPA treatment of mouse back skin. Expression of Rab11a in vivo and in vitro critically depended on c-Fos, because TPA application to the back skin of c-Fos-deficient mice and to mouse embryonic fibroblasts did not induce Rab11a mRNA or protein expression. Moreover, dexamethasone, which is a potent inhibitor of AP-1-mediated transactivation that exhibits anti-inflammatory and anti-tumor promoting activities, inhibited TPA-induced expression of Rab11a. Within the Rab11a gene promoter, we identified a functional AP-1 binding element that exhibited elevated c-Fos binding activity after TPA treatment of keratinocytes. Enhanced expression was not restricted to chemically induced mouse skin tumors but was also found in tumor specimens derived from patients with epithelial skin tumors. These data identify Rab11a as a novel, tumor-associated c-Fos/AP-1 target and may point to an as yet unrecognized function of Rab11a in the development of skin cancer. 相似文献
943.
Ndung'u T Gaseitsiwe S Sepako E Doualla-Bell F Peter T Kim S Thior I Novitsky VA Essex M 《Clinical and diagnostic laboratory immunology》2005,12(9):1020-1028
Southern Africa is facing an unprecedented public health crisis due to the high prevalence of human immunodeficiency virus type 1 (HIV-1). Vaccine development and testing efforts, mainly based on elicitation of HIV-specific T cells, are under way. To understand the role of human leukocyte antigen (HLA) class II alleles in HIV pathogenesis and to facilitate HLA-based HIV-1 vaccine design, we analyzed the frequencies of HLA class II alleles within the southern African country of Botswana. Common HLA class II alleles were identified within the Botswana population through the molecular genotyping of DRB and DQB1 loci. The DRB1 allele groups DRB1*01, DRB1*02/15, DRB1*03, DRB1*11, and DRB1*13 were encountered at frequencies above 20%. Within the DQB1 locus, DQB1*06 (47.7%) was the most common allele group, followed by DQB1*03 (39.2%) and DQB1*04 (25.8%). We found that DRB1*01 was more common in HIV-negative than in HIV-positive individuals and that those who expressed DRB1*08 had lower median viral loads. We demonstrate that the frequencies of certain HLA class II alleles in this Botswana population differ substantially from those in North American populations, including African-Americans. Common allele groups within Botswana cover large percentages of other African populations and could be targeted in regional vaccine designs. 相似文献
944.
945.
Kasper HU Longerich T Stippel DL Kern MA Drebber U Schirmacher P 《Archives of pathology & laboratory medicine》2005,129(2):234-237
We report a case in an elderly adult of a highly malignant liver tumor with blastoid features that resembled hepatoblastoma. A liver tumor with a diameter of 23 cm was removed in a 78-year-old woman. The tumor showed highly differentiated epithelial hepatocellular and poorly differentiated epithelial and mesenchymal components. The blastoid nature and pluripotent differentiation potential were supported by immunohistologic analysis and suggest an origin of a poorly differentiated pluripotent hepatic cell with the potential to mature. We believe that this case of a mixed hepatoblastoma in an adult should be added to the growing number of presumed hepatic precursor cell neoplasms in adults. 相似文献
946.
Marfan syndrome: exclusion of genetic linkage to the COL1A2 gene 总被引:11,自引:0,他引:11
Marfan Syndrome is a genetic disorder of the connective tissue. Individuals from one large family with this disorder were genotyped for COL1A2 gene associated RFLPs. Our results demonstrated that the COL1A2 gene, encoding the proa2(I) collagen chain, segregated independently of the phenotype and it is therefore excluded as the mutant locus in this family. 相似文献
947.
Tito Cavallo Eleonora G. Galvanek Peter A. Ward Franz von Lichtenberg 《The American journal of pathology》1974,76(3):433-450
The glomerular lesions induced in 10 chimpanzees infected with variable numbers of Schistosoma japonicum cercariae were studied by means of light and electron microscopy and fluorescent antibody technic. Ten animals served as controls; 5 were uninfected and 5 were only lightly infected. The animals were observed for periods ranging from 3 to 17 months, and by the time of sacrifice, all had developed advanced liver fibrosis. In general, the degree of glomerular injury was related to infection intensity and degree and duration of portal liver fibrosis. Some animals had terminal BUN elevation and slight proteinuria. By light and electron microscopy, in the initial stages, only part of the glomeruli were involved and exhibited mesangial matrix expansion and mesangial cell proliferation with intracellular hyaline droplets. At later stages, a larger number of glomeruli were affected and exhibited diffuse hypercellularity, glomerular basement thickening, mesangial sclerosis and less often, focal necrosis, crescent formation, synechiae and global hyalinization. In addition, there were discrete electron-dense deposits localized in the mesangial area in some glomeruli. Immunofluorescent studies utilizing antisera to chimpanzee γ-globulin and complement (C3) and to human properdin disclosed only faint deposits of C3, apparently in mesangial areas. The association of hepatosplenic schistosomiasis and nephropathy, the possible role of schistosomal antigen and the mechanism(s) of such glomerular injuries are reviewed and compared with the disease in humans and other host species infected with Schistosoma. 相似文献
948.
Utility of Major Leukocyte Subpopulations for Monitoring Secondary Cytomegalovirus Infections in Renal-Allograft Recipients by PCR 总被引:2,自引:1,他引:2 下载免费PDF全文
Peter Schfer Werner Tenschert Liana Cremaschi Kai Gutensohn Rainer Laufs 《Journal of clinical microbiology》1998,36(4):1008-1014
The feasibility of the major peripheral blood leukocyte (PBL) subsets for use in qualitative and quantitative PCR to monitor secondary cytomegalovirus (CMV) infection and ganciclovir therapy was assessed with 188 blood samples derived from 40 CMV immunoglobulin G-positive renal-allograft recipients. In pp65 antigen-positive patients all leukocyte fractions, but only 79.5% of plasma preparations, were PCR positive. In pp65 antigen-negative samples from patients after antiviral treatment only 7.3% of polymorphonuclear cell (PMNL) samples, but 81.8% of peripheral blood mononuclear cells (PBMC), and 10.9% of plasma samples remained PCR positive. Similarly, in patients with latent infections only 5.0% of PMNL, but 51.7% of PBMC preparations, and 8.0% of plasma samples were PCR positive. Regarding patients with active CMV infection, CMV DNA copy numbers in PMNL correlated significantly with pp65 antigen-positive cell counts before and after onset of ganciclovir therapy. Significant differences in CMV DNA copy numbers in PMNL and plasma were observed (i) between patients with symptomatic infection and those with asymptomatic infection and (ii) between patients with active infection and those with latent infection. In contrast, PBMC harbored equally low CMV DNA levels both in patients with active infection and those with latent infections, and no decline of CMV DNA load in PBMC was observed during antiviral treatment. We conclude that detection of CMV DNA in PMNL, not in PBMC, is associated with active infections and is more sensitive than detection of CMV DNA in plasma. Negative PCR results for PMNL after antiviral therapy indicate recovery, and fewer unwanted positive results occur compared to PBMC and plasma. Therefore, purified PMNL should be preferred for analysis by qualitative CMV PCR to avoid unwanted positive results. The CMV DNA load in PBMC compared with that in PMNL is negligible during active infection, so mixed PBL are sufficient for use in quantitative PCR. 相似文献
949.
Identification of a Putative Precursor to the Major Surface Glycoprotein of Pneumocystis carinii 总被引:1,自引:0,他引:1
Susan M. Sunkin Michael J. Linke Francis X. McCormack Peter D. Walzer James R. Stringer 《Infection and immunity》1998,66(2):741-746
The major surface glycoprotein (MSG) of Pneumocystis carinii f. sp. carinii is a family of proteins encoded by a family of heterogeneous genes. Messenger RNAs encoding different MSGs each begin with the same 365-bp sequence, called the Upstream Conserved Sequence (UCS), which is in frame with the contiguous MSG sequence. The UCS contains several potential start sites for translation. To determine if translation of MSG mRNAs begins in the UCS, polyclonal antiserum was raised against the 123-amino-acid peptide encoded by the UCS. The anti-UCS serum reacted with a P. carinii protein that migrated at 170 kDa; however, it did not react with the mature MSG protein, which migrates at 116 kDa. A 170-kDa protein was immunoprecipitated with anti-UCS serum and shown to react with a monoclonal antibody against a conserved MSG epitope. To explore the functional role of the UCS in the trafficking of MSG, the nucleotide sequence encoding the UCS peptide was ligated to the 5′ end of an MSG gene and incorporated into a recombinant baculovirus. Insect cells infected with the UCS-MSG hybrid gene expressed a 160-kDa protein which was N-glycosylated. By contrast, insect cells infected with a baculovirus carrying an MSG gene lacking the UCS expressed a nonglycosylated 130-kDa protein. These data suggest that in P. carinii, translation begins in the UCS to produce a pre-MSG protein, which is subsequently directed to the endoplasmic reticulum and processed to the mature form by proteolytic cleavage. 相似文献
950.
Nelson Rhodes Theresa DSouza Christine D. Foster Yael Ziv David G. Kirsch Yosef Shiloh Michael B. Kastan Peter H. Reinhart Tona M. Gilmer 《Genes & development》1998,12(23):3686-3692
Similarities exist between the progressive cerebellar ataxia in ataxia telangiectasia (AT) patients and a number of neurodegenerative diseases in both mouse and man involving specific mutations in ion channels and/or ion channel activity. These relationships led us to investigate the possibility of defective ion channel activity in AT cells. We examined changes in the membrane potential of AT fibroblasts in response to extracellular cation addition and found that the ability of AT fibroblasts to depolarize in response to increasing concentrations of extracellular K+ is significantly reduced when compared with control fibroblasts. Electrophysiological measurements performed with a number of AT cell lines, as well as two matched sets of primary AT fibroblast cultures, reveal that outward rectifier K+ currents are largely absent in AT fibroblasts in comparison with control cells. These K+ current defects can be corrected in AT fibroblasts transfected with the full-length ATM cDNA. These data implicate, for the first time, a role for ATM in the regulation of K+ channel activity and membrane potential. 相似文献