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11.
12.
Stein TP; Oram-Smith JC; Leskiw MJ; Wallace HW; Long LC; Leonard JM 《The American journal of physiology》1976,230(5):1321-1325
13.
Incomplete rescue of cystic fibrosis transmembrane conductance regulator deficient mice by the human CFTR cDNA 总被引:2,自引:2,他引:2
Rozmahel R; Gyomorey K; Plyte S; Nguyen V; Wilschanski M; Durie P; Bear CE; Tsui LC 《Human molecular genetics》1997,6(7):1153-1162
We have used a mouse model to study the ability of human CFTR to correct
the defect in mice deficient of the endogenous protein. In this model,
expression of the endogenous Cftr gene was disrupted and replaced with a
human CFTR cDNA by a gene targeted 'knock-in' event. Animals homozygous for
the gene replacement failed to show neither improved intestinal pathology
nor survival when compared to mice completely lacking CFTR. RNA analyses
showed that the human CFTR sequence was transcribed from the targeted
allele in the respiratory and intestinal epithelial cells. Furthermore, in
vivo potential difference measurements showed that basal CFTR chloride
channel activity was present in the apical membranes of both nasal and
rectal epithelial cells in all homozygous knock-in animals examined. Ussing
chamber studies showed, however, that the cAMP-mediated chloride channel
function was impaired in the intestinal tract among the majority of
homozygous knock-in animals. Hence, failure to correct the intestinal
pathology associated with loss of endogenous CFTR was related to
inefficient functional expression of the human protein in mice. These
results emphasize the need to understand the tissue- specific expression
and regulation of CFTR function when animal models are used in gene therapy
studies.
相似文献
14.
Successful outcome with day 4 embryo transfer after preimplantation diagnosis for genetically transmitted diseases 总被引:4,自引:5,他引:4
Preimplantation genetic diagnosis was performed in 61 day 3 embryos
obtained by in-vitro fertilization from seven patient carriers of
haemophilia, Marfan's syndrome, Bloch-Sulzemberg syndrome (incontinentia
pigmentosa) or X chromosome-linked immune deficiency, retinitis pigmentosa,
and FG syndrome, which is characterized by mental retardation and
hypotonia. After multiplex polymerase chain reaction, 16 embryos were
diagnosed as being unaffected, and these were transferred to the uterus on
the following day (day 4). Of these embryos, six (37.5%) implanted,
resulting in the delivery of a singleton and a twin pregnancy, a late
second trimester miscarriage (twins at week 20) and a first trimester
miscarriage at week 8. All the diagnoses were confirmed by amniocentesis.
We report for the first time a late day 4 transfer of biopsied human
embryos undergoing preimplantation genetic diagnosis. This transfer
schedule allows an extra day to perform genetic analyses on single
blastomeres and to monitor any adverse effect of the biopsy procedure.
相似文献
15.
Marjolijn Bornebroek Joost Haan Marion LC Maat-Schieman Sjoerd G Van Duinen Raymund AC Roos 《Brain pathology (Zurich, Switzerland)》1996,6(2):111-114
Hereditary cerebral hemorrhage with amyloidosis - Dutch type (HCHWA-D) is an autosomal dominant disease caused by deposition of β-amyloid in the leptomeningeal arteries and cortical arterioles, in addition to preamyloid deposits and amyloid plaques in the brain parenchyma.
The disease is due to a point mutation at codon 693 of the amyloid precursor protein (βPP) gene at chromosome 21. Since this point mutation is diagnostic for HCHWA-D, presymptomatic testing is feasible and offered, together with genetic counselling and psychological support, to subjects at risk. HCHWA-D is clinically characterized by recurrent strokes, in addition to dementia, which can occur after the first stroke but also preceding it. Radiological studies revealed focal lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse white matter damage. Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke.
The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The characteristic pathological abnormalities and its implications for Alzheimer's disease will be discussed in Part II of this article 相似文献
The disease is due to a point mutation at codon 693 of the amyloid precursor protein (βPP) gene at chromosome 21. Since this point mutation is diagnostic for HCHWA-D, presymptomatic testing is feasible and offered, together with genetic counselling and psychological support, to subjects at risk. HCHWA-D is clinically characterized by recurrent strokes, in addition to dementia, which can occur after the first stroke but also preceding it. Radiological studies revealed focal lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse white matter damage. Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke.
The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The characteristic pathological abnormalities and its implications for Alzheimer's disease will be discussed in Part II of this article 相似文献
16.
Three-generation transmission of Hirschsprung's disease 总被引:1,自引:0,他引:1
17.
Detection of precytopathic effect of enteroviruses in clinical specimens by centrifugation-enhanced antigen detection 总被引:2,自引:0,他引:2
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Rapid enterovirus detection is important for decisions about antibiotic administration and length of hospital stay. The efficacy of rapid antigen detection-cell culture amplification (Ag-CCA) was evaluated with monoclonal antibodies (MAbs) 5-D8/1 (DAKO) and Pan-Enterovirus clone 2E11 (Chemicon) with 10 poliovirus, echovirus, and coxsackievirus type A and B stock isolates and College of American Pathologists check samples. By using Ag-CCA technology, MAb 2E11 was more sensitive than 5-D8/1 at detecting a greater number of stock isolates at or past tube (cytopathic effect [CPE]) culture (TC) end points. The efficacy of Ag-CCA in the clinical setting was subsequently confirmed with 273 consecutively freshly collected nasopharyngeal aspirate or swab specimens, rectal swab, and cerebrospinal fluid specimens during the 1999 enterovirus season. All specimens were tested by Ag-CCA in parallel with rhesus monkey kidney (RhMk), MRC-5, and A549 conventional TCs. Approximately 60% of field specimens were additionally tested with Hep-2 and HNK conventional TCs. Sixty-two percent of the clinical specimens tested were Ag-CCA positive after 48 h. Among 51 isolates, the mean time to CPE or culture confirmation was 5.5 days (range, 2 to 18 days). After 48 h, Ag-CCA achieved sensitivity, specificity, and positive and negative predictive values of 62, 100, 100, and 93%, respectively. During the same period, TC-CPE displayed test parameters of 12, 100, 100, and 85%, respectively. After 5 days, the sensitivity and specificity of Ag-CCA increased to 92 and 98%, respectively. Within the same period, isolation attained sensitivity and specificity of 52 and 100%, respectively. Although Ag-CCA displayed slightly reduced sensitivity and reduced specificity compared with conventional cell culture after 14 days, the markedly superior 48-h enterovirus Ag-CCA detection rate supports incorporation of this assay into the routine clinical setting. 相似文献
18.
One hundred twelve peripheral blood specimens were tested for the presence of cytomegalovirus (CMV) by the tube culture indirect immunoperoxidase (TC-IPA) procedure, the shell vial assay [shell vials were pre- and postinoculation treated with medium containing 2 of 10% fetal bovine serum (FBS) or 100 micrograms% cortisol] (SV-IFA), and conventional (MRC-5) tube cultures (TC-CPE). CMV was detected in 25 (22%) of the 112 specimens tested by at least one of these methods. The detection/isolation of CMV among the 25 positive specimens in shell vials maintained with 2% FBS, 100 micrograms% cortisol + 2% FBS, and 10% FBS was 36, 44, and 52%, respectively. Detection/isolation of the virus from blood by TC-IPA and TC-CPE was 52% and 76%, respectively. A significantly greater CMV detection rate occurred using TC-CPE compared to SV-IFA treated with medium supplemented with an FBS concentration of 2% (P = .0132), but not medium containing the higher serum supplement or the glucocorticoid (P greater than .05). Differences in the identification of a CMV viremia were observed by IPA, SV-IFA, and TC-CPE methodologies on a patient-to-patient basis, denoting the necessity of incorporating each methodology into the CMV screening panel. Demographic analysis of 82 AIDS patients showed a CMV viremia prevalence of 9% (2/28) in intravenous drug users, 57% (27/47) in homosexual patients, and 22% (2/9) in heterosexual and transfusion patients. Overnight (24 hr) storage of whole blood at 4 or 24 degrees C, respectively, reduced CMV recovery by 40% and 65%, when tested by TC-CPE.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
19.
Feeding 0.001% estrone in a diet to C57BL/KsJ mice homozygous for the recessive obesity gene "diabetes" (db) permitted dissociation of the primary consequences of obesity gene expression from the secondary consequences of diabetes effected through interaction between the db gene and other diabetogenic genes in the inbred background. Estrone-treated db/db mice were similar to untreated mutants in exhibiting hyperphagia and marked obesity. However, estrone-treated mutants did not develop the hyperinsulinemia, hyperglycemia, and islet atrophy characteristic of untreated db/db mice. Thus, expression of the primary defect could be studied in the absence of the myriad secondary sequelae elicited by chronic hyperinsulinemia and hyperglycemia. Reduced numbers of hepatocyte plasma membrane insulin receptors (50% of normal) persisted in the estrone-treated mice in the absence of hyperinsulinemia, indicating that this deficiency was a consequence of the primary genetic defect and not merely a downregulation phenomenon secondary to hyperinsulinemia. Comparison of insulin secretion from comparably sized +/+ islets versus islets from estrone-treated db/db mice showed no intrinsic defects in beta-cell sensitivity to glucose. In conclusion, db-induced obesity can be dissociated from hyperinsulinemia, hyperglycemia, beta-cell dysfunction, and hyperphagia but is associated with a generalized membrane defect reflected in part by the persistent deficiency of plasma membrane insulin receptors. 相似文献
20.
同种异体黑素细胞移植治疗白癜风 总被引:2,自引:2,他引:0
0 引言 白癜风患者免疫紊乱 ,黑素细胞 (melanocyte,MC)异体移植有可能不被排斥 ,治疗如成功将有很大临床前景 [1 ] .探索同种异体黑素细胞移植后的效果很有意义 .1 病例报告 女 ,2 7岁 ,确诊白癜风 (稳定期 ) ,患者皮肤自幼出现色素脱失斑 ,逐渐增多扩大 . 1996年外用“敏白灵”,前2 mo有效 . 1999- 0 7外用补骨酯酊 ,日服 5 g· L- 1 硫酸铜 10m L和中药 1剂 ,转移因子 4m L ,sc,1· 2 d- 1 .皮损缩小 ,4mo后稳定 .用健康男青年环切的包皮培养 MC,第 4代大约80 %融合时 ,用 2 .5 g· L- 1 胰酶消化 5 min,加入含 2 0 0 g·L- 1小… 相似文献