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91.
Guidelines for the appropriate use of genetic tests in infertile couples 总被引:10,自引:0,他引:10
Foresta C Ferlin A Gianaroli L Dallapiccola B 《European journal of human genetics : EJHG》2002,10(5):303-312
Research on genetic causes of male and female infertility rapidly expanded in the last years, following the development of in vitro fertilising techniques. Genetic tests are now available to explore the cause of the infertility and assess the risk of a given couple to transmit its genetic characteristics. This allows at-risk couples to take an informed decision when electing for a medically assisted reproduction. It also allows the professionals to offer a prenatal diagnosis when appropriate. Thus, the genetic work-up of the infertile couple has become good practice for an appropriate diagnosis, treatment and prognostic assessment. The lack of national or international rules for the genetic approach to the infertile couple, prompted the Italian community of professionals in the field of reproductive medicine to join and set up guidelines for the genetic diagnosis of male and female infertility. The group of clinical and research experts is representative of 12 national scientific societies and was supported by external experts from four international societies. We examine the clinically relevant genetic causes of male and female infertility and suggest the category of patients for which each genetic test is recommended or optional, both for an accurate diagnosis and prior to ART. 相似文献
92.
93.
Hepatocyte growth factor (HGF), a stimulator of angiogenesis and cell migration, regulates the growth of a wide variety of
cells by binding to its high-affinity receptor met and is involved in the growth and aggressiveness of several tumors. In
this study we investigated the expression of HGF and met in normal endocrine cells and related neoplasms of the gut and pancreas
to verify their possible role in tumor pathogenesis, growth, and aggressiveness. Normal tissues and 60 different endocrine
tumors were immunostained using specific antibodies directed against HGF, met, and various hormones. HGF immunoreactivity
(IR) was found in antroduodenal G cells, rectal enterochromaffin (EC) cells, and pancreatic A and B cells, whereas met IR
was detected in antral EC and G cells, and in pancreatic B cells; 46 of 60 tumors examined were positive for HGF, and they
were mainly represented by ECL-, EC-, and L-cell neoplasms. met IR was identified in 50/60 tumors of various phenotypes. HGF
and met coexpression was found in 42/60 cases, most of which were represented by EC-cell tumors. HGF/met coexpression was
significantly more frequent in ileolonic EC-cell tumors, which in the majority of cases were malignant, than in appendiceal
EC-cell tumors, which were all benign. Our results demonstrated, for the first time, that HGF and met are specifically distributed
in normal gut and pancreatic endocrine cells and, in addition, suggest that HGF and met may be implicated as autocrine/paracrine
factors regulating the growth of gastroenteropancreatic endocrine tumors, mainly of ileocolonic EC-cell carcinoids. 相似文献
94.
Toru Furukawa Rumi Fujisaki Yoshitaro Yoshida Naomi Kanai Makoto Sunamura Tadayoshi Abe Kazunori Takeda Seiki Matsuno Akira Horii 《Modern pathology》2005,18(8):1034-1042
DUSP6/MKP-3 is identified as a candidate tumor suppressor gene for pancreatic cancer. The aim of this study was to elucidate the roles of DUSP6 in the pancreatic carcinogenesis through the pancreatic intraepithelial neoplasia and/or intraductal papillary-mucinous neoplasms, both of which are considered to be precursor lesions of invasive carcinoma of the pancreas, by comparing with involvements of other major tumor suppressive pathways. Expressions of DUSP6, CDKN2A, TP53, and SMAD4 were investigated by immunohistochemistry in a total of 206 lesions of dysplastic ductal precursors and carcinomas retrieved from 52 pancreata with invasive ductal carcinomas and 51 of those with intraductal papillary-mucinous neoplasms. The intensity of staining was evaluated in lesions at different atypical grades and statistically compared among them. Mutations of KRAS2 were analyzed by methods of the allele-specific oligonucleotide hybridization and nucleotide sequencing. In pancreata with invasive ductal carcinomas, expressions of DUSP6 were abrogated exclusively in the invasive carcinoma cells in contrast to its fairly preserved expressions in pancreatic intraepithelial neoplasia. In pancreata with intraductal papillary-mucinous neoplasms, abrogated expressions of DUSP6 were observed in a relatively small fraction of intraductal adenoma/borderlines and intraductal carcinomas. Most of the intraductal adenoma/borderline lesions with abrogation of DUSP6 harbored mutations of KRAS2. None of the molecules was associated with each other in any grade of lesions. Morphological variations of papillae of the intraductal papillary-mucinous neoplasms were evaluated and analyzed for their associations with abrogations of the molecules, which resulted in finding of no significant associations. Our results suggest that the abrogation of DUSP6 is associated exclusively with progression from pancreatic intraepithelial neoplasia to the invasive ductal carcinoma while it is potentially associated with initiation of intraductal papillary-mucinous neoplasms with mutated KRAS2, which is independent of other major tumor suppressive pathways in both types of neoplasms. 相似文献
95.
A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia 总被引:2,自引:0,他引:2
96.
Mutagenicity of drinking water is due not only to industrial,agricultural and urban pollution but also to chlorine disinfectionby-products. Furthermore, residual disinfection is used to providea partial safeguard against low level contamination and bacterialre-growth within the distribution system. The aims of this studywere to further evaluate the genotoxic potential of the worldwide used disinfectants sodium hypochlorite and chlorine dioxidein human leukocytes by the Comet assay and in Saccharomycescerevisiae strain D7 (mitotic gene conversion, point mutationand mitochondrial DNA mutability, with and without endogenousmetabolic activation) and to compare their effects with thoseof peracetic acid, proposed as an alternative disinfectant.All three disinfectants are weakly genotoxic in human leukocytes(lowest effective dose 0.2 p.p.m. for chlorine dioxide, 0.5p.p.m. for sodium hypochlorite and peracetic acid). The resultsin S.cerevisiae show a genotoxic response on the end-pointsconsidered with an effect only at doses higher (5- to 10-fold)than the concentration normally used for water disinfection;sodium hypochlorite and peracetic acid are able to induce genotoxiceffects without endogenous metabolic activation (in stationaryphase cells) whereas chlorine dioxide is effective in growingcells. The Comet assay was more sensitive than the yeast tests,with effective doses in the range normally used for water disinfectionprocesses. The biological effectiveness of the three disinfectantson S.cerevisiae proved to be strictly dependent on cell-specificphysiological/biochemical conditions. All the compounds appearto act on the DNA and peracetic acid shows effectiveness similarto sodium hypochlorite and chlorine dioxide.
1Author to whom correspondence should be addressed. Tel: +39 0521 905608; Fax: +39 0521 905604; Email: mutgen{at}unipr.it
Received on September 22, 2003; revised and accepted on November 27, 2003 相似文献
97.
Saccharomyces cerevisiae as an eukaryotic cell model to assess cytotoxicity and genotoxicity of three anticancer anthraquinones 总被引:1,自引:0,他引:1
The toxicity of most drugs is associated with their enzymatic conversion to toxic metabolites. Bioactivation reactions occur in a range of cellular organs and organelles, including mitochondria. We have investigated different effects (i.e. growth inhibition, mortality and genotoxicity) of doxorubicin, epirubicin and mitoxantrone on the D7 strain of Saccharomyces cerevisiae and on its petite (rho degrees ) respiratory-deficient mutant at various cellular concentrations of cytochrome P450 and glutathione (GSH). The data confirmed the importance of oxygen production for doxorubicin toxicity. The complete absence, or a very low level, of cytochrome oxidase subunit IV conferred some resistance to doxorubicin. Low GSH levels decreased resistance to doxorubicin in both strains, suggesting that thiol depletion could potentiate membrane lipid peroxidation. Doxorubicin induction of petite colonies suggests that the drug is able to select rather than induce respiratory-deficient mutants. Epirubicin induced levels of cytotoxicity similar to those of doxorubicin. The effects did not appear to be significantly dependent on mitochondrial function or GSH levels, whereas cells were strongly protected by cytochrome P450. GSH did not induce an evident alteration. Neither were genotoxic effects induced. Mitoxantrone had reduced levels of both growth inhibition and cytotoxicity in comparison to anthracyclines and induced convertants, revertants and aberrants. All the effects considered were amplified at high cytochrome P450 cellular concentrations, although the drug was also shown to act without previous metabolism via cytochrome P450. Anthracenedione effectiveness was increased by metabolism via cytochrome P450 and partially reduced by GSH. However, further mechanisms were suggested, which might implicate mitochondrial function and/or production of electrophilic cytotoxic and/or genotoxic intermediates by means of GSH conjugation. The biological effectiveness of doxorubicin, epirubicin and mitoxantrone on S.cerevisiae was shown to be strictly dependent on cell-specific physiological/biochemical conditions, such as a functional respiratory chain and levels of cytochrome P450 and GSH. 相似文献
98.
Evaluation of the BDProbeTec ET system for direct detection of Mycobacterium tuberculosis in pulmonary and extrapulmonary samples: a multicenter study 下载免费PDF全文
Mazzarelli G Rindi L Piccoli P Scarparo C Garzelli C Tortoli E 《Journal of clinical microbiology》2003,41(4):1779-1782
We evaluated the BDProbeTec ET system (Becton Dickinson, Sparks, Md.), a strand displacement amplification-based technique, for direct detection of Mycobacterium tuberculosis in 867 clinical samples. Of 294 extrapulmonary specimens, 52 had positive results by both BDProbeTec ET and culture and 209 had negative results by both methods; sensitivity and specificity were 76.5 and 95.9%, respectively. After resolution of discrepancies, the sensitivity rose to 77.8%. 相似文献
99.
Fausto Sessa Daniela Furlan Anna Genasetti Paola Billo Maddalena Feltri Carlo Capella 《Diagnostic molecular pathology》2003,12(2):96-102
We studied the MSI (microsatellite instability) status and p53 expression in a series of 71 gallbladder cancers (GCs) of different histologic type. All neoplasms were examined combining a microsatellite analysis at mononucleotide locus BAT-26 and an immunohistochemical study for hMSH2, hMLH1, and p53 proteins and markers of gastric and intestinal differentiation. All the 71 GCs were MSS (microsatellite stable). The p53 protein was found in 100% of undifferentiated GCs, 67% of conventional gallbladder adenocarcinomas, 50% of mucinous adenocarcinomas, and 20% GCs with squamous differentiation. All 71 MSS tumors showed presence of immunohistochemical expression of both hMLH1 and hMSH2 gene products. We concluded that microsatellite instability does not play a role in the developing of GC while p53 seems to be the most important alteration found in a large proportion of these cancers, with the only exception of mucinous and squamous gallbladder carcinomas. 相似文献
100.
Carlo M. Crocem Monica Shander Joanne Martinis Lucienne Cicurel Gian G. D'ancona Hilary Koprowski 《European journal of immunology》1980,10(6):486-488
Loss of human chromosomes from mouse × human hybridomas is not random. Human chromosomes 14, 5 and 22 are preferentially retained, while chromosomes 2 and 1 are preferentially lost. Interestingly, human chromosome 14, which carries the genes for human immunoglobulin heavy chains, appears to be retained by almost all the hybrid clones and subclones. 相似文献