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Biomedical subjects

G Wright

Publications and source records attributed to G Wright.

At least 91 records · Page 5Linked to original sources
PubMed1996

Preliminary experience with human oocyte cryopreservation using 1,2-propanediol and sucrose.

Feasibility of cryopreservation of mature human oocytes using 1, 2-propanediol and sucrose was studied initially utilizing 1 and 2 day old unfertilized oocytes. Of these 285 aged oocytes 55% survived thawing, and 41% of 128 oocytes inseminated by single sperm intracytoplasmic injection (ICSI) fertilized normally. Limited embryonic development occurred in 51% of these embryos (n = 27) observed for the next 4 days. Cryosurvival of fresh donated oocytes (n = 81) was poorer (n = 20; 24.7%), while fertilization (n = 13; 65%) and embryo development (100%) was good prior to uterine transfer on day 3. Eight oocyte recipient cycles were undertaken, in which cryopreserved donated oocytes were thawed and inseminated by ICSI. Five of these cycles reached embryo transfer, and three pregnancies were initiated though none went successfully to term. Oocyte cryopreservation will ultimately facilitate oocyte donation procedures; however, cryosurvival of fresh frozen oocytes must be improved to at least the degree observed with aged unfertilized oocytes.

Cell Survival↗
PubMed1996

Effect of retinoic acid on contractile competence of vascular smooth muscle.

Rat aortic rings cultured for 24 h in protein-free medium showed a significant reduction in the contractile response to potassium (-60%) and to phorbol 12,13-dibutyrate (-65%). The addition of plasma to the medium attenuated the loss in responsiveness, and the supplementation of the plasma-containing medium with all trans-retinoic acid (RA) returned the response to potassium (85%) and phorbol ester (135%) to near normal or supramaximal compared with fresh tissue. Furthermore, the combined additions of plasma and RA resulted in significant preservation of the contractile response (75%) for at least 3 days in organ culture. Removal of the endothelium before organ culture eliminated the enhancement of contraction by plasma and RA. However, the removal of the endothelium from tissues that had been cultured with an intact endothelium or the blockade of nitric oxide synthesis in these tissues before contractile measurements had no effect on the contractile response. Finally, the incubation of tissues with phorbol ester to downregulate protein kinase C resulted in a marked attenuation (-75%) of the contractile response compared with control tissues in culture. The results suggest that circulating factors may be necessary for the maintenance of contractile function of aortic smooth muscle. Based on the opposing actions of RA and phorbol ester, the long-term regulation of contractile function may involve protein kinase C activity.

Animals↗
PubMed1996

Serum iodothyronine concentrations in intestinally decontaminated rats treated with a 5'-deiodinase type I inhibitor 6-anilino-2-thiouracil.

Enteric bacteria have been postulated to have a role in thyroid economy by promoting the hydrolysis of thyroid hormone conjugates of biliary origin, thus permitting the absorption and recycling of thyroxine (T4) and triiodothyronine (T3). An enterohepatic circulation of T3 might be more pronounced under conditions in which type I iodothyronine deiodinase activity (5'D-I) is inhibited, because this augments the accumulation of T3 sulfate conjugates in bile. This potential of increased gut reabsorption of T3 might explain, at least in part, the failure of serum T3 values to decrease appreciably when marked reductions in peripheral 5'D-I activity are induced by selenium deficiency or 6-anilino-2-thiouracil (ATU) administration. Thus, studies were performed to determine the effect of intestinal decontamination, in the absence and in the presence of 5'D-I inhibition, on plasma T4 and T3 concentrations. Groups of adult male rats received either enteric antibiotics or no antibiotics for 12 days and then, in half of the rats in each group, treatment for 10 days with ATU, a 5'D-I inhibitor that does not affect thyroid hormone synthesis. The activity of intestinal arylsulfatase and arylsulfotransferase, enzymes that catalyze hydrolysis of thyroid hormone conjugates, was reduced markedly by approximately 87% in rats that received antibiotics, regardless of whether or not they also received ATU. The ATU treatment markedly inhibited liver 5'D-I activity in antibiotic-treated as well as in non-antibiotic-treated rats (control = 399 +/- 32 U/mg protein (mean +/- SEM); ATU = 152 +/- 17: antibiotics = 351 +/- 29; antibiotics + ATU = 130 +/- 10; p < 0.01) and significantly increased plasma T4 and T3 sulfate (T4S, T3S) concentrations (control: T4S = 2.8 +/- 0.4 and T3S = 6.7 +/- 1.3 ng/dl; ATU: T4S = 6.2 +/- 1.4 and T3S = 10.6 +/- 2.1 ng/dl; antibiotics: T4S = 1.8 +/- 0.2 and T3S = 3.6 +/- 1.0 ng/dl; antibiotics + ATU: T4S = 6.8 +/- 0.7 and T3S = 9.7 +/- 1.8 ng/dl; p < 0.05). The ATU treatment was associated with a significant increase in plasma T4 and rT3 concentrations but did not affect plasma T3 concentrations, and intestinal decontamination did not alter these ATU-associated effects on circulating thyroid hormones. These results suggest that anaerobic enteric bacteria in the rat do not have an important role in recycling of thyroid hormones, either under normal conditions or in circumstances where 5'D-I activity is markedly reduced, and that increased gut absorption of T3 from T3S cannot explain the near-normal serum T3 values found when peripheral 5'D-I activity is markedly decreased.

Aniline Compounds↗
PubMed1995

Reproductive and other factors and risk of epithelial ovarian cancer: an Australian case-control study. Survey of Women's Health Study Group.

Of the few factors known to be associated with epithelial ovarian cancer, the most consistently observed relate to women's reproductive function, although even here uncertainties remain. We have undertaken a case-control study involving personal interviews with over 1,600 women, the largest of its kind to date, to investigate further the associations between women's reproductive histories and other factors and the development of ovarian cancer. Cases were drawn from women diagnosed with epithelial ovarian cancer in 3 Australian states, Queensland, New South Wales and Victoria, between August 1990 and December 1993, and controls were drawn at random from the electoral roll, stratified by age and geographic region. Trained interviewers administered standard questionnaires to obtain detailed information about women's reproductive and contraceptive histories and other factors of interest, such as smoking and family history of ovarian or other cancer. Findings were based on data from 824 cases and 860 controls and confirmed the reduced risk of ovarian cancer associated with increasing parity and duration of use of the oral contraceptive pill (OCP), hysterectomy and tubal ligation. The strongest association of all was seen with use of the OCP for 10 years or more. An inverse association between ovarian cancer and age at first birth was observed, but this was not statistically significant. There were no associations between development of ovarian cancer and number of incomplete pregnancies, use of hormone replacement therapy or menstrual history. Among other factors considered, education after leaving school was negatively associated and high body mass index, family history of ovarian cancer, use of talc in the abdominal or perineal region and smoking were positively associated with occurrence of ovarian cancer.

Adolescent↗
PubMed1995

Prevalence of psychiatric disorders in rural South Australia.

OBJECTIVE: To determine the prevalence of psychiatric disorders and use of medical services in a South Australian rural community. DESIGN: Survey based on structured self-administered questionnaires. SETTING: Riverland region of South Australia, between May and November, 1991. SUBJECTS: A probability sample of 1009 residents (71.1%) response stratified for age and sex (with replacement) aged 18 years and over from the State electoral roll. OUTCOME MEASURES: DSM-III-R-defined psychiatric disorders diagnosed by means of the University of Washington's Diagnostic Interview Schedule Screening Instrument (DISSI), physical disorders and use of health and allied services. RESULTS: Twenty-six percent had at least one psychiatric disorder in the six months before interview. Prevalence did not differ with sex or age, but was higher in the unemployed (P=0.0001). Those with a current psychiatric disorder were significantly more likely to report a lifetime physical disorder (p=0.0001). The most common disorders were major depression and dysthymia (10.8%), anxiety disorder (9.8%), phobic disorder (7.8%), alcohol abuse and dependence (7.0% and somatisation syndrome (5.3 During the year before interview, 88.5% of those diagnosed with a current psychiatric disorder had consulted a general practitioner and 4.2% a psychiatrist or psychologist. CONCLUSIONS: The prevalence of psychiatric disorders in the Riverland region was comparatively high. General practitioners were the primary care-providers for those with psychiatric disorders. These issues need to be addressed by service providers and health planners.

Adolescent↗
PubMed1995

Proteolytic cleavage of insulin-like growth factor binding protein 4 (IGFBP-4). Localization of cleavage site to non-homologous region of native IGFBP-4.

Insulin-like growth factor binding protein 4 (IGFBP-4) is a 24-kDa protein that binds insulin-like growth factor 1 (IGF-1) and IGF-2 with high affinity and inhibits IGF action in vitro. We recently described a protease produced by the B104 neuronal cell line that cleaves IGFBP-4, yielding an approximate 16-kDa immunoreactive protein that binds IGFs with reduced affinity. We analyzed fragments produced by exposing pure IGFBP-4 to the protease to determine potential cleavage sites. Electrospray mass spectrometry and amino acid sequencing indicated the 16-kDa fragment spanned the NH2 terminus of native IGFBP-4 through Lys-120. There was evidence for an additional proteolytic fragment beginning at amino acid 132 and continuing to the COOH terminus. Proteolysis could be blocked by a synthetic peptide that spanned amino acids 117-126 but not by peptides that contained flanking sequences 111-120 or 125-135. Mutagenesis was used to alter the basic residue at position 120. The expressed mutant IGFBP-4 (K120A) was relatively resistant to cleavage, strongly suggesting that residues 120-121 represent the cleavage site. This region of IGFBP-4 is not homologous with other IGFBPs, explaining the apparent specificity of the protease for IGFBP-4. The 16-kDa IGFBP-4 fragment no longer inhibited IGF-1-stimulated thymidine uptake in vitro, suggesting that proteolytic processing of IGFBP-4 may have important functional consequences in vivo.

Amino Acid Sequence↗
PubMed1995

Effect of coculture on subsequent survival and implantation of cryopreserved human embryos.

PURPOSE: This retrospective analysis was designed to assess the performance of human embryos following cryopreservation based on whether they were originally developed in standard culture medium (65 cycles, 223 embryos) or cocultured on partial monolayers of bovine oviductal epithelial cells (63 cycles, 198 embryos). Embryo cryosurvival and implantation were compared between the study group and the contemporaneously match controls. RESULTS: During a 2-year period when no factors of the cryopreservation program were altered, 63 transfers of 159 surviving thawed control cleavage-stage embryos (71.3% survival) that were 54% intact gave rise to 11 viable pregnancies (17.5%/ET), to yield an implantation rate of 6.9% per embryo. Sixty-three transfers of 147 thawed cocultured embryos (74.2% survival) that were 61% intact gave an implantation rate of 13.6% per embryo that was significantly higher than the control group (P < 0.05). CONCLUSION: Coculture of embryos prior to cryopreservation does not appear to improve cryosurvival; however, it does improve implantation postthaw compared with embryos following standard culture prior to cryopreservation.

Animals↗
PubMed1995

Practical evolution and application of direct intracytoplasmic sperm injection for male factor and idiopathic fertilization failure infertilities.

OBJECTIVE: To analyze the introduction of a new assisted fertilization technique for the treatment of severe male factor and idiopathic fertilization failure infertilities. DESIGN: Retrospective analysis of 16-month clinical application of IVF-ET where insemination was performed solely by direct intracytoplasmic sperm injection. SETTING: Clinical IVF-ET program. PATIENTS: Ninety-two couples undergoing 105 cycles of sperm injection. RESULTS: One hundred embryo transfers yielded 28 viable pregnancies (28%) from which eight normal deliveries have occurred to date. Complete cleavage arrest or fertilization failure occurred in four cycles, and one couple had all embryos cryopreserved. One thousand one hundred forty-three eggs were injected of which 173 (15%) degenerated. Four hundred seventy-nine of the surviving 970 eggs became normally fertilized (49%), and 381 of these zygotes (79.5%) developed suitably for cryopreservation or for transfer. Thirty-four of 310 embryos transferred implanted, yielding an implantation rate of 11%. Both testicular and epididymal sperm were used successfully to achieve fertilization and pregnancies, as was sperm retrieved by electroejaculation. Older women and couples suffering from prior idiopathic fertilization failure had a markedly poorer outcome. CONCLUSIONS: These results confirm that the intracytoplasmic sperm injection technique is a successful form of assisted fertilization that can be applied to a wide range of couples at significant risk from fertilization failure.

Adult↗
PubMed1995

Factors affecting success with intracytoplasmic sperm injection.

In this study, 141 couples underwent 163 cycles of in vitro fertilization (IVF) and embryo transfer in which the eggs were inseminated by intracytoplasmic sperm injection (ICSI). Overall, 41% of the injected eggs were normally fertilized and 81% of the resulting embryos were suitable for cryopreservation (91 embryos) or uterine transfer. From 153 fresh embryo transfers, 45 ongoing or delivered pregnancies (27.6% per cycle) were achieved, and of the 507 embryos transferred, 54 successfully implanted giving an implantation rate per embryo of 10.7%. Five additional pregnancies did not yield a viable fetus or underwent a spontaneous abortion, giving a miscarriage rate of 10% (5/50). Increased maternal age or a prior diagnosis of failed fertilization after conventional IVF had a significantly negative impact on success. Sperm from the testis and epididymis, those retrieved by electro-ejaculation, and completely immotile ejaculated sperm all gave rise to pregnancies. ICSI reinsemination was used with limited success to rescue failed fertilization cycles, although the implantation rate per embryo was poor (5%). ICSI has greatly improved the ability to use IVF for treating couples with a poor fertilization potential.

Adult↗
PubMed1995

Cryopreservation of human embryos and oocytes.

Human embryo cryopreservation is now a fully established adjunct to assisted reproduction, with thawed embryos implanting at a rate approaching that of fresh embryos. As with fresh embryos, the quality of frozen-thawed embryos is affected by patient age at the time of oocyte retrieval, and by culture conditions. Ovarian stimulation incorporating gonadotropin-releasing hormone analogs does not appear to be detrimental to cryopreservation success, and natural or artificial thaw cycles seem equally effective. Successful cryopreservation seems feasible for one- to eight-cell embryos and blastocysts using a variety of protocols. Selection criteria for embryos to be frozen can vary, and embryo quality has the most significant impact on post-cryopreservation viability. Unfertilized oocyte cryopreservation is coming closer to routine clinical application.

Cryopreservation↗
PubMed1995

Lack of magainin-like activity in human cervical tissue.

PROBLEM: The cervix plays an integral role in innate immunity of the human reproductive tract. Magainins are antimicrobial and spermicidal peptides recently described in human submandibular glands. We investigated the human cervix for magainin-like peptides. METHOD: Histologic sections of frozen and paraffin embedded cervical tissue from nine subjects were separately incubated with two rabbit, polyclonal, anti-magainin antibodies (CB-2 and CB-7) to investigate for magainin-like activity in the human cervix. RESULTS: There was no specific staining of cervical columnar cells within the endocervical canal or in the endocervical crypts. Magainin-like immunoreactivity in the human submandibular gland confirmed previous observations. CONCLUSION: Antigen related to magainin-like peptides were not discovered in the human cervix.

Animals↗
PubMed1995

Persistence of sodium monofluoroacetate in rabbits and risk to non-target species.

1. Sodium monofluoroacetate (1080), a vertebrate pesticide used in New Zealand, was administered orally to rabbits at two dose levels (sub-lethal and lethal) to determine how long 1080 would persist in plasma, liver, kidney, and muscle so that the risk of consumption of meat from lethally or sub-lethally poisoned rabbits by non-target species could be assessed. 2. The plasma elimination half-life in rabbits receiving a sub-lethal dose was 1.1 h. Retention of 1080 in tissue was greater in rabbits dosed with a lethal dose than in those that received a sub-lethal dose. Irrespective of the dose level, concentration of 1080 in muscle, kidney, and liver was substantially lower than in the plasma. 3. Poisoning of dogs is possible because of their extreme susceptibility to 1080. Poisoning of birds is less likely. The risk of secondary poisoning is reduced as the concentration of 1080 declines in putrefying carcasses.

Administration, Oral↗
PubMed1995

Role of metabolic acidosis on cardiac mechanical performance during severe acute hypoxia and reoxygenation is small and transient.

OBJECTIVE: The aim was to determine whether the metabolic acidosis that develops during severe acute myocardial hypoxia improves or impairs the recovery of cardiac mechanical function during reoxygenation. METHODS: Isolated rat hearts performed external work against a model of the rat systemic vascular impedance. Four groups of 10 hearts were used for mechanical studies. In these experiments, the hearts were subjected to normoxic ventilation for 15 min, hypoxic ventilation for 20 min, and reoxygenation for 60 min. The perfusate pH was either allowed to drift downward due to metabolic acidosis, or it was corrected to 7.4 as hypoxia or reoxygenation began. Mechanical performance was assessed by measuring heart rate and model "aortic" pressure and flow and by computing left ventricular mean, pulsatile, and total hydraulic power output and stroke work. A further four groups of 10 hearts were used for biochemical studies. In these experiments, myocardial high energy phosphates and calcium content were measured at the end of the period of hypoxia. RESULTS: When no attempt was made to regulate the perfusate pH, it drifted downward from 7.40(SEM 0.01) to 7.33(0.01) during hypoxia and then to 7.25(0.02) during reoxygenation. All mechanical variables measured and computed were severely depressed by hypoxia, whether the pH was regulated or not. Left ventricular total hydraulic hydraulic power output decreased to less than 10% of the control value in all experiment groups and recovered to 86.7-91.2% of the control value after 60 min of reoxygenation. Mechanical recovery was most rapid when the correction of acidosis was delayed until reoxygenation was begun. After 5 min of reoxygenation, it had recovered to 65.5% of the control value compared with a 37.0% recovery when the pH was allowed to drift and 34.9% when the pH was corrected to 7.4 during hypoxia. However, the differences in power output became non-significant after 10 min of reoxygenation. Myocardial creatine phosphate and adenosine triphosphate concentrations were decreased by hypoxia whether the pH was corrected (63.0% and 26.9% relative to the control), or not (68.9% and 35.0% relative to the control) (not statistically significant), but total cell calcium was not affected. CONCLUSIONS: In the isolated rat heart, correction of the moderate metabolic acidosis that developed during severe acute myocardial hypoxia improved the rate of mechanical recovery, but the effect was small and not sustained.

Acidosis↗