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排序方式: 共有216条查询结果,搜索用时 10 毫秒
1.
Gene conversion is a likely cause of mutation in PKD1 总被引:3,自引:0,他引:3
Watnick TJ; Gandolph MA; Weber H; Neumann HP; Germino GG 《Human molecular genetics》1998,7(8):1239-1243
Approximately 70% of the gene responsible for the most common form of
autosomal dominant polycystic kidney disease ( PKD1 ) is replicated in
several highly homologous copies located more proximally on chromosome 16.
We recently have described a novel technique for mutation detection in the
duplicated region of PKD1 that circumvents the difficulties posed by these
homologs. We have used this method to identify two patients with a nearly
identical cluster of base pair substitutions in exon 23. Since pseudogenes
are known to be reservoirs for mutation via gene conversion events for a
number of other diseases, we decided to test whether these sequence
differences in PKD1 could have arisen as a result of this mechanism. Using
changes in restriction digest patterns, we were able to show that these
sequence substitutions are also present in N23HA, a rodent-human somatic
cell hybrid that contains only the PKD1 homologs. Moreover, these changes
were also detected in total DNA from several affected and unaffected
individuals that did not harbor this mutation in their PKD1 gene copy. This
is the first example of gene conversion in PKD1 , and our findings
highlight the importance of using gene-specific reagents in defining PKD1
mutations.
相似文献
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Gasowski J Staessen JA Celis H Fagard RH Thijs L Birkenhäger WH Bulpitt CJ Fletcher AE Arabidze GG de Leeuw P Dollery CT Duggan J Kawecka-Jaszcz K Leonetti G Nachev C Safar M Rodico JL Rosenfeld J Seux ML Tuomilehto J Webster J Yodfat Y 《Journal of human hypertension》1999,13(2):135-145
The Systolic Hypertension in Europe (Syst-Eur) trial proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older (> or = 60 years) patients with isolated systolic hypertension (systolic BP > or = 160 mm Hg and diastolic BP < 95 mm Hg). After the completion of the Syst-Eur trial on 14 February 1997, 3506 consenting patients (93.0% of those eligible) were enrolled in phase 2 of the Syst-Eur trial. This open follow-up study aims to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine. To lower the sitting systolic BP below 150 mm Hg (target BP), the first-line agent nitrendipine (10-40 mg/day) may be associated with enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), both add-on study drugs, or if required any other antihypertensive agent. On 1 November 1998, 3248 patients were still being followed, 86 patients had proceeded to non-supervised follow-up, and 43 had died. The median follow-up in Syst-Eur 2 was 14.3 months. At the last available visit, systolic/diastolic BP in the patients formerly randomised to placebo (n = 1682) or active treatment (n = 1824), had decreased by 13.2/5.2 mm Hg and by 4.6/1.6 mm Hg, respectively, so that the between-group BP difference was 1.7 mm Hg systolic (95% Ci: 0.8 to 2.6 mm Hg; P < 0.001) and 0.9 mm Hg diastolic (95% Cl: 0.4 to 1.5 mm mm Hg; P < 0.001). At the beginning of Syst-Eur 2, the goal BP was reached by 25.4% and 50.6% of the former placebo and active-treatment groups; at the last visit these proportions were 55.9% and 63.1%, respectively. At that moment, 45.9% of the patients were on monotherapy with nitrendipine, 29.3% took nitrendipine in combination with other study drugs. Until the end of 2001, BP control of the Syst-Eur 2 patients will be further improved. Cardiovascular complications and adverse events, such as cancer or gastro-intestinal bleeding, will be monitored and validated by blinded experts. 相似文献
4.
BACKGROUND & AIMS: Shwachman syndrome is an inherited condition with multisystemic abnormalities, including exocrine pancreatic dysfunction. The aim of this study was to evaluate the occurrence and progression of features in a large cohort of patients. METHODS: Clinical records of 25 patients with Shwachman syndrome were reviewed. RESULTS: Mean birth weight (2.92 +/- 0.51 kg) was at the 25th percentile. However, by 6 months of age, mean heights and weights were less than the 5th percentile. After 6 months of age, growth velocity was normal. Severe fat maldigestion due to pancreatic insufficiency was present in early life (fecal fat, 26% +/- 17% of fat intake; age, < 2 years). Serial assessment of exocrine pancreatic function showed persistent deficits of enzyme secretion, but 45% of patients showed moderate age-related improvements leading to pancreatic sufficiency. Neutropenia was the most common hematologic abnormality (88%), but leukopenia, thrombocytopenia, and anemia were also frequently encountered. Patients with hypoplasia of all three bone marrow cellular lines (n = 11) had the worst prognosis; 5 patients died, 2 of sepsis and 3 of acute myelogenous leukemia. Other findings included hepatomegaly and/or abnormal liver function test results and skeletal abnormalities. CONCLUSIONS: A wide and varied spectrum of phenotypic abnormalities among patients with Shwachman syndrome is described. Pancreatic acinar dysfunction is an invariable abnormality. Patients with severe bone marrow involvement may have a guarded prognosis. (Gastroenterology 1996 Dec;111(6):1593-602) 相似文献
5.
Prostaglandin E2 (PGE2) is produced by activated platelets and by several other cells, including capillary endothelial cells. PGE2 exerts a dual effect on platelet aggregation: inhibitory, at high, supraphysiologic concentrations, and potentiating, at low concentrations. No information exists on the biochemical mechanisms through which PGE2 exerts its proaggregatory effect on human platelets. We have evaluated the activity of PGE2 on human platelets and have analyzed the second messenger pathways involved. PGE2 (5 to 500 nmol/L) significantly enhanced aggregation induced by subthreshold concentrations of U46619, thrombin, adenosine diphosphate (ADP), and phorbol 12-myristate 13-acetate (PMA) without simultaneously increasing calcium transients. At a high concentration (50 mumol/L), PGE2 inhibited both aggregation and calcium movements. PGE2 (5 to 500 nmol/L) significantly enhanced secretion of beta-thromboglobulin (beta TG) and adenosine triphosphate from U46619- and ADP-stimulated platelets, but it did not affect platelet shape change. PGE2 also increased the binding of radiolabeled fibrinogen to the platelet surface and increased the phosphorylation of the 47-kD protein in 32P- labeled platelets stimulated with subthreshold doses of U46619. Finally, the amplification of U46619-induced aggregation by PGE2 (500 nmol/L) was abolished by four different protein kinase C (PKC) inhibitors (calphostin C, staurosporine, H7, and TMB8). Our results suggest that PGE2 exerts its facilitating activity on agonist-induced platelet activation by priming PKC to activation by other agonists. PGE2 potentiates platelet activation at concentrations produced by activated platelets and may thus be of pathophysiologic relevance. 相似文献
6.
Interleukin-6 enhances growth factor-dependent proliferation of the blast cells of acute myeloblastic leukemia 总被引:7,自引:0,他引:7
The effects of recombinant interleukin-6 (IL-6) on the proliferation of blast precursors present in the peripheral blood of patients with acute myeloblastic leukemia (AML) was investigated. IL-6 had little effect by itself; however, it synergized with granulocyte macrophage colony- stimulating factor (GM-CSF) and interleukin-3 (IL-3) in the stimulation of AML blast colony formation. Responsiveness of blast progenitors to IL-6 was heterogeneous. On normal bone marrow cells the same synergy was observed on granulocyte and monocyte precursors (GM-CFC), while there was no significant effect on erythroid and multipotential precursors. 相似文献
7.
The morphological picture of bioptic renal tissue was studied in 23 patients with different forms of vasorenal hypertension, among whom 12 had fibromuscular dysplasia of the renal arteries, 8 had atherosclerotic stenosis, and 3 had panarteritis of the aorta and its branches with involvement of the renal arteries. The syndrome of malignant hypertension was encountered in 13 patients and stable arterial hypertension with high blood pressure levels in 10 patients. Analysis of the bioptic material allowed it to be divided into two groups: the 1st was marked by a picture of "Selye's kidney" and the 2nd by a combination of stenosis of the renal arteries and parenchymatous diseases of the kidneys. The significance of examining the morphological picture of renal bioptates, both with regard to the study of the pathogenesis of vasorenal hypertension and the diagnosis of concomitant parenchymatous process is shown. 相似文献
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