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81.
Schover LR; Thomas AJ; Falcone T; Attaran M; Goldberg J 《Human reproduction (Oxford, England)》1998,13(4):862-866
Many couples undergoing in-vitro fertilization (IVF) are at a higher risk
of having a child with a genetic abnormality. In a sample of 55 consecutive
couples starting IVF, only 33% had no genetic risk factor. The most common
genetic risks were advanced maternal age and possible abnormalities
associated with severe male infertility. Despite education on these risks,
71% of couples had no interest in receiving formal genetic counselling.
Only 14% of couples at risk would consider using a gamete donor to avoid
transmitting a genetic disorder to a child. The triple test to screen for
fetal abnormalities was acceptable to 82% of couples, but only 47% planned
to have amniocentesis or chorionic villi sampling. Couples were
significantly more likely to opt for prenatal testing if they would
consider terminating a pregnancy should the fetus have a severe genetic
abnormality (P < 0.01). Roman Catholic couples tended to have more
conservative attitudes about pregnancy termination. Socio-economic status
and whether the infertility factor was male or female were not predictors
of a couple's attitudes.
相似文献
82.
Optimization of a method for deactivation of platelet-activating factor:acetylhydrolase in serum for use in in-vitro fertilization culture media 总被引:1,自引:0,他引:1
Embryos produced by in-vitro fertilization (IVF) may produce less
platelet-activating factor (PAF) than is optimal for development. It was
previously shown that supplementation of culture media with PAF results in
a significant increase in pregnancy rate. Human embryos are often cultured
in media supplemented with serum containing the enzyme PAF:acetylhydrolase
(PAF:AH; EC 3.1.1.47), which hydrolyses PAF to its inactive form, lyso-PAF.
Thus, effective supplementation of media with PAF requires inactivation of
this enzyme. In this study we examine the efficacy of the methods of PAF:AH
deactivation used for PAF supplementation of IVF culture medium. When the
effectiveness of a commonly used acid treatment protocol (pH 3.0 at room
temperature for 5 min) was examined, it was found that it was not
completely effective for the majority of sera. When synthetic PAF was added
to 18 serum samples which had been acid treated, five had 90-100% of the
original PAF remaining after 24 h (showing that the acid treatment was
effective), eight had from 10-90% of the original PAF remaining after 24 h,
and five samples had 0-10%. The extent to which PAF:AH was susceptible to
deactivation was not associated with the activity in the serum prior to
treatment, the serum oestradiol concentration, or the cause of infertility.
The period of acidification and the incubation temperature were assessed to
develop a new acid-treatment protocol (20 min acid treatment at 37 degrees
C) which was able to deactivate PAF:AH effectively in all sera (53/53)
examined. A trial was performed to assess the effect of acid treatment of
serum for 5 min at room temperature compared with the new protocol (20 min
at 37 degrees C) on IVF outcome, following PAF supplementation of IVF
culture medium. Oocyte recovery, fertilization and embryo development rates
were equivalent for both groups and approximately equal numbers of embryos
were transferred or cryopreserved. Pregnancy rates were not significantly
different (14.6 versus 20.0%) for the two treatments, with a trend towards
a higher pregnancy rate with the new acid- treatment protocol. The results
show that this new procedure for acid treatment of serum in combination
with PAF supplementation does not have detrimental effects on embryos and
their pregnancy outcome and is therefore suitable for use in IVF.
相似文献
83.
Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC1 总被引:6,自引:7,他引:6
Roepman R; van Duijnhoven G; Rosenberg T; Pinckers AJ; Bleeker-Wagemakers LM; Bergen AA; Post J; Beck A; Reinhardt R; Ropers HH; Cremers FP; Berger W 《Human molecular genetics》1996,5(7):1035-1041
The gene for retinitis pigmentosa 3 (RP3), the most frequent form of X-
linked RP (XLRP), has been mapped previously to a chromosome interval of
less than 1000 kbp between the DXS1110 marker and the OTC locus at
Xp21.1-p11.4. Employing a novel technique, YAC Representation Hybridization
(YRH)', we have recently identified a small XLRP associated microdeletion
in this interval, as well as several putative exons including the 3' end of
a gene that was truncated by the deletion. cDNA library screening and
sequencing of a cosmid centromeric to the deletion has now enabled us to
identify numerous additional exons and to detect several point mutations in
patients with XLRP. The predicted gene product shows homology to RCC1, the
guanine-nucleotide- exchange factor (GEF) of the Ras-like GTPase Ran. Our
findings suggest that we have cloned the long-sought RP3 gene, and that it
may encode the GEF of a retina-specific GTP-binding protein.
相似文献
84.
The t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene 总被引:4,自引:2,他引:4
85.
Segel MJ Aqeilan R Zilka K Lorberboum-Galski H Wallach-Dayan SB Conner MW Christensen TG Breuer R 《International journal of experimental pathology》2005,86(5):279-288
The role of lymphocytes in the pathogenesis of lung fibrosis is not clear, but the weight of the evidence supports a pro-fibrotic effect for lymphocytes. The high-affinity interleukin-2 receptor (haIL-2R) is expressed on activated, but not quiescent, T lymphocytes. This selective expression of haIL-2R provides the basis for therapeutic strategies that target IL-2R-expressing cells. We hypothesized that elimination of activated lymphocytes by IL-2R-targeted chimeric proteins might ameliorate lung fibrosis. We investigated the effects of IL-2-Bax, a novel apoptosis-inducing IL-2R-targeted chimeric protein, on bleomycin-induced lung injury in mice. Treatment groups included (i) a single intratracheal instillation of bleomycin and twice-daily intraperitoneal injections of IL-2-Bax; (ii) intratracheal bleomycin and intraperitoneal IL-2-PE66(4Glu), an older-generation chimeric protein; (iii) intratracheal bleomycin/intraperitoneal PBS; (iv) intratracheal saline/intraperitoneal PBS. Lung injury was evaluated 14 days after intratracheal instillation by cell count in bronchoalveolar lavage (BAL) fluid, semi-quantitative and quantitative histomorphological measurements and by biochemical analysis of lung hydroxyproline. Bleomycin induced a BAL lymphocytosis that was significantly attenuated by IL-2-Bax and IL-2-PE66(4Glu). However, morphometric parameters and lung hydroxyproline were unaffected by the chimeric proteins. These results show that IL-2-Bax reduces the lymphocytic infiltration of the lungs in response to bleomycin, but this effect is not accompanied by a decrease in lung fibrosis. 相似文献
86.
Kleta R Skovby F Christensen E Rosenberg T Gahl WA Anikster Y 《Molecular genetics and metabolism》2002,76(3):201-206
Type III 3-methylglutaconic aciduria (MGA) (MIM 258501) consists of early bilateral optic atrophy, later development of spasticity, extrapyramidal dysfunction and occasionally cognitive deficits, and urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid. The presence of the disorder in an Iraqi-Jewish genetic isolate led to mapping of the OPA3 gene to chromosome 19q13.2-q13.3, followed by isolation of the gene itself. OPA3 consists of two exons and codes for a peptide of 179 amino acids. Iraqi-Jewish patients with type III MGA are homozygous for a splice site founder mutation in OPA3 (IVS1-1G>C) which abolishes mRNA expression in fibroblasts. Here we report a novel mutation in OPA3 (320-337del) in a Kurdish-Turkish patient with optic atrophy and 3-methylglutaconic and 3-methylglutaric aciduria, previously carrying the diagnosis of type IV MGA. We conclude that type III MGA occurs in patients of non-Iraqi-Jewish ancestry, and should be considered in patients with type IV MGA that have optic atrophy and ataxia. 相似文献
87.
Phenylketonuria (PKU) is caused by deficiency of phenylalanine hydroxylase (PAH) and increased levels of phenylalanine. PAH requires the cofactor BH(4) to function and the rate-limiting step in the synthesis of BH(4) is GTP cyclohydrolase I (GTP-CH). The skin is a potential target tissue for PKU gene therapy. We have previously shown that overexpression of PAH and GTP-CH in primary human keratinocytes leads to high levels of phenylalanine clearance without BH(4) supplementation [Gene Ther. 7 (2000) 1971]. Here, we investigate the capacity of fibroblasts, another cell type from the skin, to metabolize phenylalanine. After retroviral gene transfer of PAH and GTP-CH both normal and PKU patient fibroblasts were able to metabolize phenylalanine, however, in lower amounts compared to genetically modified keratinocytes. Further comparative analyses between keratinocytes and fibroblasts revealed a higher copy number of transgenes in keratinocytes and also a higher metabolic capacity. 相似文献
88.
S. Aabo J. P. Christensen M. S. Chadfield B. Carstensen J. E. Olsen M. Bisgaard 《Avian pathology》2002,31(1):41-47
The aim of the present study was to compare the invasion of selected zoonotic Salmonella serotypes of poultry in an in vivo chicken intestinal loop model and also in vitro in epithelial cell cultures. Invasion was measured relative to a reference strain, Salmonella Typhimurium 4/74 inv H201::Tn phoA . Two serotypes demonstrated intracellular log 10 counts that differed significantly from all other serotypes tested: Salmonella Enteritidis PT4 being 1.5 log 10 colony forming units (CFU) (31-fold) higher, and Salmonella Tennessee being 0.7 log 10 CFU (fivefold) lower than the reference strain ( P h 0.0001). A group of serotypes, which can be vertically transmitted, showed significantly higher intracellular counts (fourfold to eightfold) than the reference strain. The group included S. Typhimurium 4/74, S. Typhimurium DT104 (poultry and porcine isolates), S. Enteritidis PT1, S. Enteritidis PT6, S. Enteritidis PT8, and Salmonella Berta. The serotypes Salmonella Hadar, Salmonella Virchow, S. 4,12:b:-, S. Typhimurium DT41, and Salmonella Infantis, most of which are considered horizontally transmitted, did not show significantly different intracellular counts from the reference strain. Results from the cell culture invasion studies agreed with the in vivo data, with the exception of S. Berta and the poultry isolate of S. Typhimurium DT104. 相似文献
89.
Coagulation and complement activation 总被引:7,自引:0,他引:7
The purpose of this investigation was to assess the effect of heparin coating of a new stent construction (Stent Graft, Jomed Implantate GmbH, Germany) on platelet and coagulation activity. METHODS: Stent grafts with an ePTFE membrane interfoliated between two stents were deployed in tubings to form Chandler loops. Fresh human blood with a low concentration of heparin was rotated for 1 h, then collected and used for measurements of platelet number, thrombin-antithrombin complex (TAT), CD11b, C3a and C5b-9. There were five study groups: Group 1, conventional unmodified stents (n = 8); Group 2, untreated stent grafts (n = 8); Group 3, heparin-coated stents and untreated membrane (n = 7); Group 4, heparin-coated stents and membrane (n = 8); Group 5, heparin-coated PVC tubings with no stents (n = 8). RESULTS: There was a significant drop in platelet count, increase in TAT-values and CD11b expression in Groups 1-3 but not in Group 4 compared to Group 5. Examination by scanning electron microscopy revealed extensive activation on non-modified stents but almost no deposition of thrombotic material on heparin-modified stent grafts. CONCLUSIONS: With unmodified stents and membrane there were signs of significant activation of platelets and coagulation. In contrast, the heparin-coated stent graft induced much less alterations, indicating improved blood compatibility. 相似文献
90.
Somatic mutation processes at a human minisatellite 总被引:6,自引:3,他引:6
Germline instability at human minisatellites frequently involves complex
inter-allelic transfers of repeat units usually restricted to one end of
the repeat array and apparently regulated by flanking DNA. In contrast,
nothing is known about the structural basis of somatic instability at
minisatellites. An electrophoretic size-enrichment strategy was therefore
developed at minisatellite MS32 (D1S8) to enable rare abnormal-length
mutants to be detected, validated and quantitated in blood DNA by single
molecule PCR. Structural analysis of rare mutant alleles in blood revealed
simple deletions/duplications of repeat unit blocks located at random along
the tandem repeat array, a mode of mutation completely different from that
seen in sperm. Furthermore, allele-specific suppression of sperm
instability at MS32 did not affect somatic instability. These data suggest
that conversion-based minisatellite mutation in sperm is completely
germline-specific and most likely meiotic in origin. Somatic instability
appears to occur by a separate pathway involving replication slippage or,
more likely, intra-allelic unequal crossing over.
相似文献