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31.
Permeation of human ovarian tissue with cryoprotective agents in preparation for cryopreservation 总被引:18,自引:10,他引:18
Newton H; Fisher J; Arnold JR; Pegg DE; Faddy MJ; Gosden RG 《Human reproduction (Oxford, England)》1998,13(2):376-380
The recent improvements in the treatment of cancer by chemo- and
radiotherapy have led to a significant increase in the survival rates of
patients with malignant disease, but at the expense of distressing side
effects. One major problem, especially for younger patients, is that
aggressive therapy destroys a significant proportion of the follicular
population, which can result in either temporary or permanent infertility.
Freeze-banking pieces of ovarian cortex prior to treatment is one strategy
for preserving fecundity. When the patient is in remission, fertility
could, theoretically, be restored by autografting the thawed tissue at the
orthotopic site or by growing isolated follicles to maturity in vitro.
Recent studies have found good follicular survival in frozen-thawed human
ovarian tissue but to optimize the process an effective cryopreservation
method needs to be developed. An essential part of such a technique is to
permeate the tissue with a cryoprotectant to minimize ice formation and the
extent of this equilibration is an important determinant of post-thaw
cellular survival. In the current study, we have investigated the diffusion
of four cryoprotective agents into human tissue at both 4 degrees C and 37
degrees C. We have also studied the effect of adding different
concentrations of the non penetrating cryoprotective agent, sucrose, to the
freezing media using the release of lactate dehydrogenase as a measure of
its protective effect. At 4 degrees C propylene glycol and glycerol
penetrated the tissue significantly slower than either ethylene glycol or
dimethyl sulphoxide. At the higher temperature of 37 degrees C all four
cryoprotectants penetrated at a faster rate, however concern about enhanced
toxicity prevents the use of these conditions in practice. Thus, the
results suggest that the best method of preparing tissue for freezing is
exposure for 30 min to 1.5 M solutions of ethylene glycol or dimethyl
sulphoxide at 4 degrees C; this achieved a mean tissue concentration that
was almost 80% that of the bathing solution. We also report that the
addition of low concentrations of sucrose to the freezing medium does not
have a significant protective effect against freezing injury.
相似文献
32.
We have developed a sandwich-type ELISA system for measuring total IgD levels in the serum of atopics and non-atopic controls. In this ELISA system, affinity purified goat anti-human IgD was used for capture. Results were superior to those obtained with monoclonal anti-human IgD antibody. No cross-reactivity could be demonstrated to IgG, IgM, IgA or IgE. The assay showed minimal non-specific binding even with initial serum dilutions of 1:2. The results obtained were reproducible among replicates (Mean CV +/- SEM = 0.03 +/- 0.002; n = 251), between dilutions (CV = 0.08 +/- 0.006; n = 108), and between assays (CV = 0.05 +/- 0.12; n = 5). We used routine radioimmunoassay for measuring total serum IgE. Using these assays total serum IgD and IgE levels were measured in 75 atopic patients and 33 normal subjects. None of the atopics had recent immunotherapy. As expected, the geometric mean serum IgE in atopics (373 ng/ml) was significantly higher than that in normal subjects (49 ng/ml) (P less than 0.01). However, geometric mean serum IgD was also significantly higher in atopics (20.3 micrograms/ml) than that in normal subjects (8.4 micrograms/ml) (P less than 0.02). In both atopic and normal groups, mean serum IgD level did not differ significantly on the bases of age, sex or asthmatic status. Furthermore, total serum IgD was not significantly correlated with total serum IgE (r = 0.14; P = 0.14; n = 108), indicating that immunoregulatory control of the basal levels of the two isotypes is not linked.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
33.
Mutations in the TSC2 gene: analysis of the complete coding sequence using the protein truncation test (PTT) 总被引:4,自引:0,他引:4
Mutations in the TSC2 gene on chromosome 16p13.3 are responsible for
approximately 50% of familial tuberous sclerosis (TSC). The gene has 41
small exons spanning 45 kb of genomic DNA and encoding a 5.5 kb mRNA. Large
germline deletions of TSC2 occur in <5% of cases, and a number of small
intragenic mutations have been described. We analysed mRNA from 18
unrelated cases of TSC for TSC2 mutations using the protein truncation test
(PTT). Three cases were predicted to be TSC2 mutations on the basis of
linkage analysis or because a hamartoma from the patient showed loss of
heterozygosity for 16p13.3 markers. Three overlapping PCR products,
covering the complete coding sequence of mRNA, were generated from
lymphoblastoid cell lines, translated into 35S-methionine labelled protein,
and analysed by SDS-PAGE. PCR products showing PTT shifts were directly
sequenced, and mutations confirmed by restriction enzyme digestion where
possible. Six PTT shifts were identified. Five of these were caused by
mutations predicted to produce a truncated protein: (i) a sporadic case
showed a 32 bp deletion in exon 11, and a mutant mRNA without exon 11 was
produced; the normal exon 10 was also spliced out; (ii) a sporadic case had
a 1 bp deletion in exon 12 (1634delT); (iii) a TSC2-linked mother and
daughter pair had a G-->T transversion in exon 23 (G2715T) introducing a
cryptic splice site causing a 29 bp truncation of mRNA from exon 23; (iv) a
sporadic case showed a 2 bp deletion in exon 36; (v) a sporadic case showed
a 1 bp insertion disrupting the donor splice site of exon 37 (5007+2insA),
resulting in the use of an upstream exonic cryptic splice site to cause a
29 bp truncation of mRNA from exon 37. In one case, the PTT shift was
explained by in-frame splicing out of exon 10, in the presence of a normal
exon 10 genomic sequence. Alternative splicing of exon 10 of the TSC2 gene
may be a normal variant. Three 3rd base substitution polymorphisms were
also detected during direct sequencing of PCR products. Confirmed mutations
were identified in 28% of the families studied and on the assumption that
half of the sporadic cases should have TSC2 mutations, a crude estimate of
the detection rate would be 60%. This compares favourably with other
screening methods used for TSC2, notably SSCP, and since PTT involves much
less work it may be the method of choice.
相似文献
34.
Characterization of melanocyte stimulating hormone receptor variant alleles in twins with red hair 总被引:7,自引:3,他引:7
The association between MSHR coding region variation and hair colour in
humans has been examined by genotyping 25 red haired and 62 non-red
Caucasians, all of whom were 12 years of age and members of a twin pair
study. Twelve amino acid substitutions were seen at 11 different sites,
nine of these being newly described MSHR variants. The previously reported
Val92Met allele shows no association with hair colour, but the three
alleles Arg151Cys, Arg160Trp and Asp294His were associated with red hair
and one Val60Leu variant was most frequent in fair/blonde and light brown
hair colours. Variant MSHR genotypes are associated with lighter skin types
and red hair (P < 0.001). However, comparison of the MSHR genotypes in
dizygotic twin pairs discordant for red hair colour indicates that the MSHR
gene cannot be solely responsible for the red hair phenotype, since five of
13 pairs tested had both haplotypes identical by state (with three of the
five having both identical by descent). Rather, it is likely that
additional modifier genes exist, making variance in the MSHR gene necessary
but not always sufficient, for red hair production.
相似文献
35.
Mahadevaiah SK; Odorisio T; Elliott DJ; Rattigan A; Szot M; Laval SH; Washburn LL; McCarrey JR; Cattanach BM; Lovell-Badge R; Burgoyne PS 《Human molecular genetics》1998,7(4):715-727
An RNA-binding motif (RBM) gene family has been identified on the human Y
chromosome that maps to the same deletion interval as the 'azoospermia
factor' (AZF). We have identified the homologous gene family (Rbm) on the
mouse Y with a view to investigating the proposal that this gene family
plays a role in spermatogenesis. At least 25 and probably >50 copies of
Rbm are present on the mouse Y chromosome short arm located between Sry and
the centromere. As in the human, a role in spermatogenesis is indicated by
a germ cell-specific pattern of expression in the testis, but there are
distinct differences in the pattern of expression between the two species.
Mice carrying the deletion Yd1, that maps to the proximal Y short arm, are
female due to a position effect resulting in non-expression of Sry ;
sex-reversing such mice with an Sry transgene produces males with a high
incidence of abnormal sperm, making this the third deletion interval on the
mouse Y that affects some aspect of spermatogenesis. Most of the copies of
Rbm map to this deletion interval, and the Yd1males have markedly reduced
Rbm expression, suggesting that RBM deficiency may be responsible for, or
contribute to, the abnormal sperm development. In man, deletion of the
functional copies of RBM is associated with meiotic arrest rather than
sperm anomalies; however, the different effects of deletion are consistent
with the differences in expression between the two species.
相似文献
36.
Vaughan JR; Farrer MJ; Wszolek ZK; Gasser T; Durr A; Agid Y; Bonifati V; DeMichele G; Volpe G; Lincoln S; Breteler M; Meco G; Brice A; Marsden CD; Hardy J; Wood NW 《Human molecular genetics》1998,7(4):751-753
A mutation in exon 4 of the human alpha-synuclein gene was reported
recently in four families with autosomal dominant Parkinson's disease (PD).
In order to examine whether mutations in this exon or elsewhere in the gene
are common in familial PD, all seven exons of the alpha- synuclein gene
were amplified by PCR from index cases of 30 European and American
Caucasian kindreds affected with autosomal dominant PD. Each product was
sequenced directly and examined for mutations in the open reading frame. No
mutations were found in any of the samples examined. We conclude that the
A53T change described in the alpha- synuclein gene is a rare cause of PD or
may even be a rare variant. Mutations in the regulatory or intronic regions
of the gene were not excluded by this study.
相似文献
37.
38.
Peter A. Shapiro Richard P. Sloan Emilia Bagiella J. Thomas Bigger JR. Jack M. Gorman 《Psychophysiology》1996,33(1):54-62
Heart rate reactivity to mental stress is substantially blunted early after heart transplantation, suggesting that the loss of neural modulation limits the cardiovascular response to mental stress. We tested whether reactivity to mental stress recovers during the first year after heart transplantation. Hemodynamic and respiratory responses to mental arithmetic challenge were studied in 20 heart transplant recipients 3, 6, and 12 months after surgery. A normal comparison group was studied at equivalent intervals. Heart rate reactivity to mental arithmetic was significantly reduced in the cardiac transplant group compared to the normal subjects. This effect persisted up to 1 year after transplantation. Heart period variability in the heart transplant recipients was minimal in all three-test sessions. The findings suggest that no functional reinnervation or other compensatory adaptation occurs up to 1 year after heart transplantation. 相似文献
39.
IgG antibody to gE, the Fc gamma-binding herpes simplex 1 (HSV-1) viral glycoprotein, was studied in 49 rheumatoid arthritis (RA) patients and 43 normal controls. Antibody to gD, another important HSV-1 antigen, was assayed in parallel. No difference between RA patients and normal controls was found in levels of anti-gE antibody measured by reactivity of IgG F(ab')2 fragments reacting with gE coated to ELISA plates. No difference in anti-gD antibody was recorded between normals and patients with RA. Levels of IgG anti-IgE antibody did not correlate with quantitative elevations of serum rheumatoid factor (RF) in RA patients. When IgG anti-gE and anti-gD were assayed in 20 patients with juvenile rheumatoid arthritis and 22 children controls, no significant differences were noted. However, when individual RFs from patients with RA were tested for reactivity against a panel of affinity-isolated F(ab')2 antibodies to gE, some evidence for individual autospecificity was obtained. Four of 20 monoclonal IgM RFs produced from RA patients' B cells showed marked elevations of reactivity with some RA patients' F(ab')2 antibodies to gE. All four of the monoclonal RFs showing this specificity were derived from RA synovial tissue B cells. These findings may provide support for the concept that some RFs in patients with RA show individual specificity for internal image determinants of IgG antibodies to viral Fc gamma-binding proteins. 相似文献
40.