PubMed Health⌕ Search

Biomedical subjects

C Bain

Publications and source records attributed to C Bain.

At least 55 records · Page 3Linked to original sources
PubMed1996

Cloning of cDNAs encoding the human gamma-aminobutyric acid type A receptor alpha 6 subunit and characterization of the pharmacology of alpha 6-containing receptors.

A cDNA encoding the human gamma-aminobutyric acidA (GABAA) receptor alpha 6 subunit has been cloned and sequenced. The deduced amino acid sequence of this cDNA shows 91.4% identity with the published rat alpha 6 subunit. In situ hybridization histochemistry reveals the alpha 6 mRNA to be located within the granule cell layer of the human cerebellar cortex. Recombinant human alpha 6 beta gamma 2S GABAA receptors have been expressed in both stably transfected cells and Xenopus oocytes, and the pharmacology of the benzodiazepine binding site has been determined. The recombinant receptor has a diazepam-insensitive pharmacology, with negligible affinity for a number of classic benzodiazepines. A number of compounds that bind to the benzodiazepine site potentiated the GABA response of alpha 6 beta 2 gamma 2 receptors. Most importantly, the classic benzodiazepine antagonist ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a] [1,4]benzodiazepine-3-carboxylate (Ro 15-1788) and the partial inverse agonist ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a] [1,4]benzodiazepine-3-carboxylate (Ro 15-4513) both acted as agonists at the alpha 6 containing receptor. This observation demonstrates definitively that efficacy of benzodiazepine compounds cannot be generalized across receptor subtypes and may also help explain some of the behavioral effects that have been reported for these compounds.

Amino Acid Sequence↗
PubMed1995

Randomized trial of intake of fat, fiber, and beta carotene to prevent colorectal adenomas.

BACKGROUND: Epidemiologic evidence of associations between the high intake of fat and low intake of dietary fiber, beta carotene, and other dietary constituents and the risk of colorectal neoplasia has been inconsistent and has not provided a sufficient basis for recommendations concerning the dietary prevention of large-bowel cancer in humans. PURPOSE: We conducted a clinical trial to assess the effects on the incidence of adenomas of reducing dietary fat to 25% of total calories and supplementing the diet with 25 g of wheat bran daily and a capsule of beta carotene (20 mg daily). METHODS: We performed a randomized, partially double-blinded, placebo-controlled factorial trial in which half the patients were assigned to each intervention, resulting in seven intervention groups and one control group. Eligibility criteria included histologic confirmation of at least one colorectal adenoma and confidence expressed by the colonoscopist that all polyps had been removed. Dietary changes were individually initiated and monitored by dietitians and research nurses. At surveillance colonoscopy, the size and location of all polyps were recorded, and their histology was later centrally reviewed. Among 424 patients who were randomly assigned in the trial, 13 were found to be ineligible upon histologic review. Among the remaining 411, complete outcome data were collected from 390 at 24 months and from 306 at 48 months. All P values are from two-sided tests of statistical significance. RESULTS: There was no statistically significant prevention of total new adenomas with any of the interventions. We found a statistically non-significant reduced risk of large adenomas (> or = 10 mm) with the low-fat intervention: At 24 months, the odds ratio (OR) adjusted for potential confounders = 0.4 and 95% confidence interval (CI) = 0.1-1.1; at 48 months, OR = 0.3 and 95% CI = 0.1-1.0. Less and statistically nonsignificant reductions in the risk of large adenomas were found with wheat bran: At 24 months, OR = 0.8 and 95% CI = 0.3-2.2; at 48 months, OR = 0.8 and 95% CI = 0.3-2.5. Patients on the combined intervention of low fat and added wheat bran had zero large adenomas at both 24 and 48 months, a statistically significant finding (P = .03). CONCLUSIONS: Because only small numbers of patients were studied, our finding that the combination of fat reduction and a supplement of wheat bran reduced the incidence of large adenomas in this randomized, controlled trial must be treated with caution. The results do suggest, however, that these interventions may reduce the transition from smaller to larger adenomas, a step that may critically define those adenomas most likely to progress to malignancy.

Adenoma↗
PubMed1995

Somatic mutations of von Hippel-Lindau (VHL) tumor-suppressor gene in European kidney cancers.

Somatic mutations of von Hippel Lindau (VHL) tumor-suppressor gene have been identified in kidney cancers from North America and Japan. We studied VHL gene mutation in 31 kidney tumors from France. Of these tumors, 45% (14/31) displayed mutations, 60% of which occurred at A:T base pairs. The frequency and the spectrum of mutations identified in kidney tumors from Europe were similar to those reported for tumors from other geographical locations.

Adult↗
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

How accurate is self-reported family history of colorectal cancer?

Much of the evidence that supports a relation between a positive family history of and increased risk for colorectal cancer is based on information obtained exclusively from patients. There have been few assessments of the accuracy of such data. The validity of self-reported family history of colorectal cancer was assessed in the course of a case-control study of colorectal adenomas conducted among patients aged 20-75 years who underwent colonoscopy in Brisbane, Australia between 1980 and 1985. Family histories reported by a subsample of 237 colonoscopy patients (74 cases and 163 controls) were compared with relatives' medical records and death certificates. Patients' reports of colorectal cancer in 90 relatives were confirmed for 70 (77.8%; 95% confidence interval (CI) 67.8-85.9). Among 124 reports by patients of relatives who had other abdominal cancer or bowel conditions, 114 (91.9%; 95% CI 85.7-96.1) were confirmed to be correct, while 10 (8.1%) were found to be colorectal cancer. Finally, 105 (99.1%; 95% CI 94.9-100.0) of a random sample of 106 completely negative reports by patients were confirmed to be correct. Overall, 77% of positive family histories (any positive relatives) were confirmed, and it was estimated that 98% of negative family histories (no positive relatives) were correct. Cases were slightly more accurate than controls in reporting both positive and negative histories among their relatives. By extrapolation of these results to the total sample of 1,244 patients in the larger case-control study, sensitivity of self-reported positive family history was estimated to be 0.87 among cases and 0.82 among controls, and specificity was estimated to be 0.97 in both groups.

Adult↗
PubMed1995

Clinical application of retroviral gene transfer in oncology: results of a French study with tumor-infiltrating lymphocytes transduced with the gene of resistance to neomycin.

PURPOSE: Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and interleukin-2 (IL-2) has been reported to mediate tumor regression in some human cancers. To define better the biologic characteristics of TIL, especially survival and distribution in vivo, we performed a gene-marker study in patients with advanced malignancies. PATIENTS AND METHODS: We treated five patients with metastatic melanoma or renal cell carcinoma with adoptive immunotherapy. TIL were genetically modified, before their infusion, using a recombinant retroviral vector that contained the marker gene coding for resistance to neomycin (NeoR). RESULTS: All of the patients tolerated the treatment well and none of the theoretic safety hazards due to the retroviral gene transduction was observed. The presence of the NeoR gene in TIL was detected by Southern blot analysis, with an efficiency of transduction that ranged from 1% to 26%. With polymerase chain reaction (PCR) analysis, we demonstrated that gene-modified TIL can survive for several months after reinjection, since positive blood samples were observed up to day 260 following reinjection. Eight malignant biopsy specimens were obtained from three patients after cell infusion. TIL were detected in only four of these eight tumor deposits on days 7 and 260. CONCLUSION: These results confirm the feasibility and safety of using in vitro retroviral gene transduction in human lymphocytes to analyze their in vivo distribution for further therapeutic applications. However, a selective and prolonged retention of TIL at the tumor site was not found in this study.

Adult↗
PubMed1994

The modulatory action of loreclezole at the gamma-aminobutyric acid type A receptor is determined by a single amino acid in the beta 2 and beta 3 subunit.

Type A gamma-aminobutyric acid (GABAA) receptors of the mammalian nervous system are a family of ligand-gated ion channels probably formed from the coassembly of different subunits (alpha 1-6, beta 1-3, gamma 1-3, delta) in the arrangement alpha beta gamma or alpha beta delta. The activation of these receptors by GABA can be modulated by a range of compounds acting at distinct allosteric sites. One such compound is the broad-spectrum anticonvulsant loreclezole, which we have recently shown to act via a specific modulatory site on the beta subunit of the GABAA receptor. The action of loreclezole depends on the type of beta subunit present in the receptor complex; receptors containing beta 2 or beta 3 subunits have > 300-fold higher affinity for loreclezole than receptors containing a beta 1 subunit. We have used this property to identify the amino acid residue in the beta subunit that determines the subunit selectivity of loreclezole. Chimeric beta 1/beta 2 human GABAA receptor subunits were constructed and coexpressed in Xenopus oocytes with human alpha 1 and gamma 2s subunits. The chimera beta 1/beta 2Lys237-Gly334 conferred sensitivity to 1 microM loreclezole. Within this region there are four amino acids that are conserved in beta 2 and beta 3 but differ in beta 1. By mutating single amino acids of the beta 1 subunit to the beta 2/beta 3 equivalent, only the beta 1 mutation of Ser-290-->Asn conferred potentiation by loreclezole. Similarly, mutation of the homologous residue in the beta 2 and beta 3 subunits to the beta 1 equivalent (Asn-->Ser) resulted in loss of sensitivity to loreclezole. The affinity for GABA and the potentiation by flunitrazepam were unchanged in receptors containing the mutated beta subunits. Thus, a single amino acid, beta 2 Asn-289 (beta 3 Asn-290), located at the carboxyl-terminal end of the putative channel-lining domain TM2, confers sensitivity to the modulatory effects of loreclezole.

Allosteric Site↗
PubMed1994

Cloning, functional coexpression, and pharmacological characterisation of human cDNAs encoding NMDA receptor NR1 and NR2A subunits.

Using expression cloning, and more recently using polymerase chain reaction cloning approaches, a family of rat N-methyl-D-aspartate (NMDA) receptor subunit cDNAs has been described (NR1, NR2A, NR2B, NR2C, and NR2D). Here we report cloning and sequencing of cDNAs encoding isoforms of the human NR1 subunit (NR1a, NR1d, and NR1e) that differ at their C-terminal end as a result of alternative splicing and also of a cDNA encoding the human NR2A subunit. The deduced amino acid sequences of the human NR1 subunit isoforms differed from the published rat NR1 subunit sequences at only eight positions, all of which were N-terminal to the alternatively spliced domains. The human NR2A subunit deduced amino acid sequence differed from the published rat NR2A subunit sequence at 81 of the 1,464 amino acids, with most of the substitutions being located in the C-terminal half of the subunit. The gene for NR2A has been localised to human chromosome 16. We also report the expression and pharmacological characterisation of recombinant human NR1a/NR2A heteromeric receptors in Xenopus oocytes. These receptors had EC50 values of 2.14 and 2.05 microM for glutamate and glycine, respectively, and an IC50 of 46.8 microM for Mg2+. Responses were antagonised by D-2-amino-5-phosphonovalerate, L-689,560, pH 6.3, zinc, and MK-801. No modulatory effect was observed on application of ifenprodil, confirming previous observations with rat NR1 + NR2A recombinant receptors.

Amino Acid Sequence↗
PubMed1993

Relation between anthropometric indicators and risk of breast cancer among Australian women.

Associations between various anthropometric indicators and breast cancer were investigated in a community-based case-control study conducted among 456 premenopausal women (135 cases) and 656 women who were at least 10 years past menopause (185 cases) in Brisbane, Australia, from 1981 to 1985. Among postmenopausal women, increased risk was associated with greater weight at age 25 years (p trend = 0.002) and with a heavier maximum weight (p trend = 0.003), but not with recent weight. Results were similar for relative weight (weight (kg)/height (m)1.5). Overall, weight gain was unrelated to the occurrence of breast cancer, although risks were elevated among postmenopausal women who weighed less at age 25 (< 54 kg) and subsequently experienced a large weight gain (> 13 kg). Among premenopausal women, there was little indication that body size or change in weight was related to breast cancer. These results suggest that both heaviness in early adulthood and a large maximum weight at any time are associated with elevated risks for postmenopausal breast cancer.

Adult↗
PubMed1993

Caesarean section audit by peer review.

OBJECTIVE: To provide activity audit data on 50 consecutive caesarean sections and assess the justification for the decision to perform each caesarean section. DESIGN: A retrospective audit with peer review. SETTING: Aberdeen Maternity Hospital. SUBJECTS: Fifty consecutive women undergoing caesarean section. The peer review was undertaken by four consultants and four registrars. MAIN OUTCOME MEASURES: The proportions of caesarean sections by indication stratified according to primiparae or multiparae and emergency or elective procedures. The auditors were asked 'do you think caesarean section was reasonable?' RESULTS: There were 18 (36%) elective caesarean sections and 32 (64%) emergency procedures. Of the 25 (50%) parous women, 14 (56%) had a previous caesarean section and of these 12 (86%) had an elective repeat caesarean section. Foetal distress was the principal indication for emergency caesarean section in 20 (63%) women, with foetal blood sampling performed in only four cases. For emergency caesarean sections the decision to delivery interval ranged from 13 to 160 min (mean 50 min). At least one auditor disagreed with the decision to perform caesarean section in 24 (48%) cases. Between observers the range of disagreement was from 2 to 18 of the decisions. In only 6 (33%) of the 18 elective procedures was there complete agreement. Four (67%) of these women had two previous caesarean sections. There was complete agreement with 20 (63%) of the 32 emergency caesarean sections. Conclusions--Interventions considered as a result of this audit include the introduction of structured diagnostic criteria for caesarean section indications and peer review by the on-call team of the caesarean sections performed in the preceding 24 h.

Adolescent↗
PubMed1993

Diet and melanoma. An exploratory case-control study.

This population-based case-control study contrasted nutrient intakes of 41 women with cutaneous malignant melanoma to those of 297 women sampled from the same community (Brisbane, Australia). Diet was assessed by a comprehensive food frequency questionnaire. The strong inverse relation we observed between high intakes of polyunsaturated fatty acids and melanoma (P < 0.01) adds sufficient weight to prior findings for this persisting causal hypothesis to be abandoned. A relatively strong association with alcohol was observed: Women drinking 20 g or more (two or more drinks) daily had 2.5 (odds ratio) times the risk of melanoma as nondrinkers (95% confidence interval, 0.87 to 7.4). However, previous data are inconsistent. With regard to potential protective factors, our data fit with prior speculation that antioxidants (beta-carotene and vitamin E), zinc, and iron warrant further investigation. The nonsignificant (P = 0.18) 40% reduction in risk seen for those eating the most fish (> or = 15 g daily versus < 5 g) suggests the effects of marine oils and omega-3 fatty acids may deserve specific attention.

Adult↗
PubMed1993

Epidemiological overview of oestrogen replacement and cardiovascular disease.

In contrast to numerous epidemiological studies of prevention in men, there has been limited research into the prevention of cardiovascular disease in women. Nevertheless, sufficient data have accumulated showing that OeRT does protect against circulatory disease in women, although evidence regarding the true magnitude of that protection remains incomplete. The best estimates of the relationship between OeRT and CVD come from population-based prospective studies which are remarkably consistent: overall they indicate a 40% reduction in CVD with use of OeRT. However, because of the underlying better health of the postmenopausal women who use hormone replacement therapy, this result probably overestimates the benefit of OeRT by an unknown degree. Furthermore, details of OeRT formulation (especially the influence of regimens with an added progestin), dose, duration, and route of administration have not been adequately studied, and the evidence regarding the effect of OeRT on rates of stroke is equivocal and requires clarification. Oestrogen's cardioprotection appears to derive from favourable effects on serum lipoprotein profiles. There may also be a direct effect on the arterial system. Detrimental influences of OeRT on haemostatic function seem unlikely. Definitive information about the actual size of effects of commonly-used regimens of OeRT on cardiovascular disease and intermediate endpoints such as serum lipid concentrations can only be obtained through large-scale randomized controlled trials. Even if the reduction in CVD were modest, the mortality rates of CVD in our society are still so high that widespread use of oestrogen replacement therapy would result in substantial numbers of women's lives being saved.

Aged↗
PubMed1993

Role of the beta subunit in determining the pharmacology of human gamma-aminobutyric acid type A receptors.

A cDNA encoding the human gamma-aminobutyric acid (GABA)A receptor beta 2 subunit has been cloned and sequenced. The deduced amino acid sequence of this cDNA shows only a single amino acid change from the rat sequence (Asn-347 in rat, serine in human). Using polymerase chain reaction amplification of human-specific products from human x rodent somatic cell hybrid DNAs, the gene has been assigned to human chromosome 6. By expressing recombinant human GABAA receptors containing different beta subunits (beta 1, beta 2 or beta 3) in both transfected cells and Xenopus oocytes, we have been able to determine the influence of the beta subunit on the pharmacology of the receptor. For a number of benzodiazepine binding site compounds, a barbiturate, and several neurosteroids, neither the affinity nor the efficacy of the compounds is influenced by the type of beta subunit present in the receptor molecule. These data suggest that the beta subunit does not significantly influence the benzodiazepine, barbiturate, or steriod site pharmacologies of human GABAA receptor subtypes.

Amino Acid Sequence↗
PubMed1992

Measles herd immunity. The association of attack rates with immunization rates in preschool children.

OBJECTIVE: To examine the association between incidence of measles and immunization coverage among preschool-age children. DESIGN: An ecological study in which measles incidence was compared with immunization coverage among census tracts. The independent effects of race and population density were controlled for. SETTING: A recent measles outbreak in Milwaukee, Wis. Immunization coverage data were estimated from a retrospective, school-based survey of Milwaukee grade school students. PATIENTS: One thousand eleven persons (less than or equal to 17 years) who had confirmed measles from September 1989 through June 1990. MAIN OUTCOME MEASURES: Confirmed measles cases grouped by census tract, corresponding census tract preoutbreak immunization coverage, racial breakdown, and population density. RESULTS: Census tracts stratified into four levels, with mean immunization rates of 50.4%, 60.2%, 69.9%, and 81.0%, had respective median attack rates of 11.6, 5.0, 1.7, and 0.0 cases per 1000 persons (P less than .01). The association between immunization coverage and measles attack rate remained significant even after controlling for race and population density. CONCLUSIONS: Modest improvements in low levels of immunization coverage among 2-year-olds confer substantial protection against measles outbreaks. Coverage of 80% or less may be sufficient to prevent sustained measles outbreaks in an urban community.

Adolescent↗
PubMed1992

Protection of cells capable of reconstituting long-term bone marrow stromal cultures from 4-hydroperoxycyclophosphamide by interleukin 1 and tumor necrosis factor.

The cytokines interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) have been implicated in protecting normal hematopoiesis from both irradiation and chemotherapy damage. The mechanism of action of these cytokines and which cells are protected is not known. In this study, we report on the ability of IL-1 and TNF-alpha to protect hematopoietic cells capable of repopulating irradiated long-term bone marrow stromal cultures from 4-hydroperoxycyclophosphamide (4-HC). Irradiated long-term bone marrow cultures recharged with hematopoietic cells pretreated with IL-1 and TNF-alpha prior to 4-HC were shown to give rise to greater numbers of colony-forming cells at 4-5 weeks of culture within both the nonadherent and adherent cell populations of the long-term cultures when compared to controls. These results suggest that IL-1 and TNF-alpha can protect human long-term culture-initiating cells, which are closely related to reconstituting stem cells.

Bone Marrow↗
PubMed1991

Recurrence rate and complications after beta irradiation for pterygia.

Of 1102 consecutive patients treated with beta irradiation after pterygium removal at the Queensland Radium Institute from 1973 through 1978, 503 had a follow-up ophthalmologic examination in 1989, while a further 82 had at least a 10-year follow-up from ophthalmologic records. One hundred forty-two patients were lost to follow-up because of death, lack of cooperation, and geographical inaccessibility. A further 375 patients could not be located. Of those not followed for at least 10 years, 162 had a follow-up, recorded from ophthalmologic records, of at least 3 months. After an average dose of 22 Gray, there was a recurrence rate of 12%. A further 13% showed some sign of scleromalacia, which included 4.5% of the study group who had severe thinning.

Adult↗
PubMed1991

A profile of Australian women practicing breast self-examination.

Breast self-examination (BSE) and medical breast examination practices were studied in a group of 1,103 women without diagnosed breast cancer, randomly sampled to conform in age and social status with breast cancer cases from the population of Brisbane, Australia between 1981 and 1985. Relationships between these practices and sociodemographic factors, breast cancer risk indicators, health related behaviors and source of knowledge about BSE were analyzed. Overall, 63% of women reported performing BSE. BSE was practiced frequently (monthly or more). BSE frequency was only weakly associated with breast cancer risk indicators. It was more strongly linked with age, the 20-44 year group being more likely to examine their breasts occasionally and the women 65 years and over being less likely to examine their breasts. Married women were the most likely to practice BSE frequently and widowed or single women most likely never to practice. Women who underwent cervical smear testing were more likely to perform BSE than those who did not have smear tests. Women who learned BSE from their doctors as opposed to other sources practiced BSE more frequently and were more likely to practice BSE exactly as taught.

Adult↗