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排序方式: 共有676条查询结果,搜索用时 187 毫秒
1.
Novel heteroplasmic mtDNA mutation in a family with heterogeneous clinical presentations. 总被引:1,自引:0,他引:1
P Corona E Lamantea M Greco F Carrara A Agostino D Guidetti M T Dotti C Mariotti M Zeviani 《Annals of neurology》2002,51(1):118-122
The protean manifestations of a novel maternally inherited point mutation of the mitochondrial genome are reported. The proband showed isolated, spastic paraparesis. A brother, who had suffered from a multisystem progressive disorder, ultimately died of cardiomyopathy. Another brother is healthy. The proband's mother showed truncal ataxia, dysarthria, severe hearing loss, mental regression, ptosis, ophthalmoparesis, distal cyclones, and diabetes mellitus. A muscle biopsy performed in the proband failed to show the morphological abnormalities typical of mitochondrial disorders; the activities of respiratory chain complexes were normal. However, complex I and IV activities were low in the muscle homogenate of the affected mother and brother. Sequence analysis of mtDNA showed a heteroplasmic mutation of the tRNA(Ile) gene (G4284A). The mutation load was approximately 55%, 80%, and 90% in the muscle mtDNA of the proband, his mother, and his affected brother, respectively. Mutation was undetected in the healthy brother, as well as in 100 control samples. Several cybrid clones containing homoplasmic mutant mtDNA from the proband showed significant reductions of complex IV activity and maximum oxygen consumption rate, compared with homoplasmic wild-type clones derived from the same subject. 相似文献
2.
Chronic exposure of humans to benzene (BZ), a myelotoxin, causes aplastic anemia and acute leukemia. The stromal macrophage that produces interleukin-1 (IL-1), a cytokine essential for hematopoiesis, is a target of BZ's toxicity. Monocyte dysfunction and decreased IL-1 production have been shown to be involved in aplastic anemia in humans. Hydroquinone (HQ), a toxic bone marrow (BM) metabolite of BZ, causes time- and concentration-dependent inhibition of processing of the 34-Kd pre-interleukin-1 alpha (IL-1 alpha) to the 17-Kd mature cytokine in murine P388D1 macrophages and BM stromal macrophages, as measured by Western immunoblots of cell lysate proteins using a polyclonal rabbit antimurine IL-1 alpha antibody. HQ over a 10-fold concentration range had no effect on the lipopolysaccharide (LPS)-induced production of pre- IL-1 alpha precursor or on cell viability or DNA and protein synthesis. Stromal macrophages obtained from the femoral BM of C57Bl/6 mice exposed to BZ (600 or 800 mg/kg body weight) for 2 days were incapable of processing the 34-Kd pre-IL-1 alpha to the mature 17-Kd cytokine when stimulated in culture with LPS. Stromal macrophages from mice coadministered BZ and indomethacin, a prostaglandin H synthase (PHS) inhibitor that has been shown to prevent BZ-induced myelotoxic and genotoxic effects in mice when coadministered with benzene were able to convert the pre-IL-1 alpha to mature cytokine. Administration of recombinant murine IL-1 alpha (rMuIL-1 alpha) to mice before a dose of BZ that causes severe depression of BM cellularity completely prevents BM depression, most probably by bypassing the inability of the stromal macrophage in BZ-treated animals to process pre-IL-1 alpha to the mature cytokine. 相似文献
3.
M Carrara S Zampiron F Capolongo L Cima P Giusti 《European journal of pharmacology》1990,179(3):301-305
The effects of glycine on morphine-induced antinociception were investigated in mice, using a cutaneous thermal test (hot-plate), a visceral chemical test (acetylcholine writhing test), and a locomotor activity test. When glycine (200 mg/kg p.o.) and morphine (5 mg/kg s.c.) were given together during the first 30 min, glycine first antagonized the morphine-induced antinociception then this was followed by a synergistic effect. The two-phase influence of glycine on morphine-induced antinociception may be due to the interaction of glycine with different receptors. 相似文献
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Selected RD1 Peptides for Active Tuberculosis Diagnosis: Comparison of a Gamma Interferon Whole-Blood Enzyme-Linked Immunosorbent Assay and an Enzyme-Linked Immunospot Assay
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Delia Goletti Donatella Vincenti Stefania Carrara Ornella Butera Federica Bizzoni Giuliana Bernardini Massimo Amicosante Enrico Girardi 《Clinical and Vaccine Immunology : CVI》2005,12(11):1311-1316
We recently set up a gamma interferon (IFN-γ) enzyme-linked immunospot assay (ELISPOT), using selected early secreted antigenic target 6 (ESAT-6) peptides, that appears specific for active tuberculosis (A-TB). However, ELISPOT is difficult to automate. Thus, the objective of this study was to determine if the same selected peptides may be used in a technique more suitable for routine work in clinical laboratories, such as whole-blood enzyme-linked immunosorbent assay (WBE). For this purpose, 27 patients with A-TB and 41 control patients were enrolled. Our WBE, using the already described selected peptides from ESAT-6 plus three new ones from culture filtrate protein 10, was performed, and data were compared with those obtained by ELISPOT. Using our selected peptides, IFN-γ production, evaluated by both WBE and ELISPOT, was significantly higher in patients with A-TB than in controls (P < 0.0001). Statistical analysis showed a good correlation between the results obtained by WBE and ELISPOT (r = 0.80, P < 0.001). To substantiate our data, we compared our WBE results with those obtained by QuantiFERON-TB Gold, a whole-blood assay based on region of difference 1 (RD1) overlapping peptides approved for TB infection diagnosis. We observed a slightly higher sensitivity with QuantiFERON-TB Gold than with our WBE (89% versus 81%); however, our test provided a better specificity result (90% versus 68%). In conclusion, results obtained by WBE based on selected RD1 peptides significantly correlate with those generated by ELISPOT. Moreover, our assay appears more specific for A-TB diagnosis than QuantiFERON-TB Gold, and thus it may represent a complementary tool for A-TB diagnosis for routine use in clinical laboratories. 相似文献
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8.
Background
Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population. 相似文献9.
Genuardi M Carrara S Anti M Ponz de Leòn M Viel A 《European journal of human genetics : EJHG》1999,7(7):778-782
To determine the role played by MLH1 and MSH2 missense variants in cancer susceptibility, we have investigated the following genetic and biological characteristics associated with six MLH1 and four MSH2 missense changes identified in Italian hereditary nonpolyposis colorectal cancer (HNPCC) families: co-segregation with disease phenotype and/or bonafide pathogenetic mutations; presence of the variant in healthy control subjects; evolutionary conservation of the involved aminoacid and type of aminoacid change; and presence/absence of microsatellite instability (MSI) in tumour DNA. Overall, nine variants did not fulfil > or = 2 pathogenicity criteria. MSI was investigated in tumour samples from carriers of nine different missense mutations. Only 3/9 variants were associated with MSI in tumour DNA. In addition, four variants were not present in affected pedigree members, and five variants were observed in the control population. Based upon these results, we conclude that most MLH1 and MSH2 missense changes are unlikely to act as major causative factors in colorectal cancer susceptibility and development. 相似文献
10.
Direct evidence for the involvement of carbohydrate sequences in human sperm-zona pellucida binding 总被引:2,自引:0,他引:2
Several lines of evidence indicate that mammalian fertilization is
initiated via a binding process that is dependent upon the recognition of
oligosaccharide sequences associated with zona pellucida (ZP)
glycoproteins. Here, specific chemical and enzymatic methods were employed
to modify human ZP and to test their effects on sperm binding in the
hemizona assay system (HZA). Periodate oxidation of human ZP under very
mild conditions (10 min, 0 degrees C, 1 mM sodium m- periodate) that
attacks only terminal sialic acid resulted in a 30% loss of human sperm
binding in the HZA [hemizona index (HZI) = 70.2 +/- 10.9, n = 22; P <
0.05]. Periodate oxidation under mild conditions (1 h, 23 degrees C, 10 mM
sodium m-periodate) caused a 40% decrease in binding (HZI = 60.8 +/- 10.3;
n = 24; P< 0.01). Treatment of human ZP with neuraminidase caused a
substantial increase in sperm binding to human ZP (HZI = 297 +/- 45, n =
22; P < 0.01). These findings indicate that there are sialic acid
dependent binding sites coexisting with binding sites that are obscured by
sialic acid. To determine the periodate sensitivity of these obscured
sites, hemizona were first digested with neuraminidase and subsequently
subjected to mild periodate oxidation. The combined enzymatic and chemical
treatments caused a 79% decrease in sperm binding compared to control
hemizona (HZI = 20.7 +/- 4.4, n = 16; P < 0.001). Human sperm-ZP
interaction was also increased by digestion of human ZP with
endo-beta-galactosidase (HZI = 710 +/- 232, n = 14; P < 0.01),
indicating that potential binding sites for spermatozoa are also obscured
by lactosaminoglycan sequences. These studies support a definitive role for
the involvement of ZP-associated glycans in the binding of human
spermatozoa to oocytes.
相似文献