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Biomedical subjects

A Green

Publications and source records attributed to A Green.

At least 343 records · Page 19Linked to original sources

Roulette mutagenesis of the FMN-binding site of Klebsiella pneumoniae flavodoxin.

A method of randomising specific regions of coding sequences has been devised which utilises the Lac phenotype to identify mutants. Intact genes can be mutagenised, making it unnecessary to reclone the mutations before examining mutant phenotypes. The method has been applied to three residues around the N-terminus of the first alpha helix of the Klebsiella pneumoniae nitrogenase flavodoxin, which are predicted to form part of the phosphate-binding subsite. Surprisingly, most substitutions at Gly12, a highly conserved residue in the chain reversal preceding the alpha helix, appeared to be fairly stable in vivo and were found to retain some function. Substitutions at Lys13, a surface residue which contributes to a patch of positive charge characteristic of the nitrogenase flavodoxins, had no major effect on stability or function. However, most substitutions at Thr14, which is predicted to hydrogen bond to the phosphate of the prosthetic group FMN, were much more destabilising and grossly reduced function. The exceptions were Ala, Cys, Ser and Val, which suggests that the bulk of the residue at this position is critical.

Amino Acid Sequence↗

Menopausal symptoms in Australian women.

OBJECTIVES: To describe Australian-born women's experience of symptoms during the natural menopause transition and the relative contribution of menopausal and health status, social factors and lifestyle behaviours. DESIGN: A community based cross-sectional survey by telephone interview was carried out on a randomly derived sample of Melbourne women. PARTICIPANTS: The participants were 2000 Australian-born women, aged between 45 and 55 years. OUTCOME MEASURES: A list of 22 symptoms was used. Explanatory variables were: sociodemographic variables; menopausal and health status; lifestyle behaviours; attitudes to ageing and to menopause. RESULTS: A 70% response rate was achieved for eligible women who could be contacted during the study. Premenopausal women were the least symptomatic and perimenopausal women the most symptomatic. Factor analysis found seven common factors from the 22 symptoms studied. Menopausal status based on menstrual history was significantly related to two groups of symptoms: vasomotor symptoms, which increased through the menopausal transition; and general somatic symptoms which were more frequent in the perimenopause. Analysis of variance of factor scores found fewer symptoms with increasing years of education, better self-rated health, the use of fewer non-prescription medications, the absence of chronic health conditions, a low level of interpersonal stress, the absence of premenstrual complaints, not currently smoking, exercise at least once a week, and positive attitudes to ageing and menopause. CONCLUSIONS: Many factors unrelated to hormonal changes contributed to the symptoms. Longitudinal investigation is needed to determine the relative importance of hormonal, psychosocial and lifestyle variables in the aetiology of mid-life symptoms.

Attitude↗

Site distribution of cutaneous melanoma in Queensland.

The age-adjusted incidence rates of cutaneous melanoma in Queensland in 1987 have been analysed for 16 anatomic sites, taking into account their surface areas. In men, the incidence of invasive melanoma on the ears, a chronically sun-exposed site, was extraordinarily high with annual rates of over 200 per 10(5) units of surface area in the Queensland population. Next highest rates of over 100 melanomas per 10(5) units were found on the face, neck, shoulders and back in men and the face and shoulders in women. Comparison with site-specific incidence rates in the same population 7 1/2 years previously showed that incidence of invasive disease had significantly increased for all these sites, though the largest relative increase in this period occurred on the forearm in both men and women. Melanoma was very rare on the buttocks of both sexes and on the scalp in women, sites which receive the least sun exposure. These findings are consistent with the theory that excessive total sun exposure plays a major role in the aetiology of cutaneous melanoma.

Adult↗

A microtitre plate method for measuring biopterin with cryopreserved Crithidia fasciculata.

The assay of biopterin derivatives in dried blood spots is used by us in initial screening for inherited defects in tetrahydrobiopterin synthesis. The previously described method (1) required aseptic technique and microbiological facilities. The modification detailed here has the advantages of antibiotic cover, which overcomes these needs and microtitre plate technology allowing the incubation time to be halved with precision and accuracy retained. Data reduction facilities may be applied.

Adult↗

Increasing prevalence of juvenile onset type 1 (insulin-dependent) diabetes mellitus in Sardinia: the military service approach.

In order to obtain new and more detailed information about temporal trends and geographic distribution of Type 1 (insulin-dependent) diabetes mellitus in Sardinia, we screened a series of birth cohorts (1936-1973) of all male army conscripts aged 18-19 years, filed in the Sardinian Conscript Register where Type 1 diabetes is a cause of rejection. A total of 678 diabetic subjects, born and permanently residing in Sardinia, was identified. The point prevalence (x 1000) at the age of 20 years in the birth cohorts ranged from values close to zero for the first ten cohorts (1936-1945) up to a maximum of 3.08 (95% confidence limits 2.28-4.08) for the 1966 cohort and continued high thereafter although an apparent decrease was observed from the early 1970s birth cohorts. Type 1 diabetes was distributed throughout the four provinces of Sardinia with no particularly significant heterogeneity; however, in accordance with the geographical distribution of diabetes cases of the Eurodiab Ace survey (1989-1990), the highest prevalence of the disease was observed in the Cagliari and Oristano provinces, followed by Nuoro and Sassari. These data suggest a gradually increasing trend of male Type 1 diabetes prevalence in Sardinia with a 29-fold increase between the late 1930s and the late 1960s birth cohorts. This seems to confirm the high incidence of Type 1 diabetes in the 0-14 and 0-29 year age groups recently reported among Sardinians during the Eurodiab Ace collaborative multicentre study.

Adolescent↗

Biochemical stability during parenteral nutrition in children.

The aim of this study was to assess the frequency and importance of biochemical abnormality related to parenteral nutrition (PN) in a group of infants, and to devise an appropriate policy for routine biochemical surveillance. A standard monitoring protocol based on widely published guidelines was applied to 30 consecutive patients (age 3 days-3 years) referred to a children's hospital nutritional care team for PN. No serious biochemical abnormalities were observed to arise simply as a consequence of PN. Electrolyte disturbance most commonly occurred before starting PN. Biochemical abnormality was most likely to be found in patients with abnormal fluid and electrolyte losses. Protocols for biochemical surveillance during PN err on the side of caution and often suggest frequent and comprehensive testing. In stable patients such as the surgical newborn, this is both expensive and unnecessary, and simpler monitoring regimes may be used with safety.

Journal Article↗

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↗

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↗

Comparability of surrogate and self-reported information on melanoma risk factors.

Surrogate reports by patients about their relatives, and vice versa, are potentially of great use in studies of the genetic and environmental causes of the familial aggregation of cancer. To assess the quality of such information in a family study of melanoma aetiology in Queensland, Australia, the authors compared surrogate reports with self-reports of standard melanoma risk factors obtained by mailed self-administered questionnaire. There was moderate agreement between surrogate reports provided by the cases and relatives' self-reports for questions on ability to tan (polychoric correlation coefficient (pc) = 0.60), skin colour (pc = 0.57), average propensity to burn (pc = 0.56), and hair colour at age 21 (kappa coefficient = 0.55), although relatives in the extreme risk factor categories were misclassified by surrogates at least half of the time. Agreement was lower for questions on degree of moliness (pc = 0.45), tendency to acute sunburn (pc = 0.42), and number of episodes of painful sunburn (pc = 0.23). The quality of relatives' surrogate reports about cases was similar to that of cases' surrogate reports about relatives. Cases who reported a family history of melanoma provided better surrogate information than did cases who indicated no family history, and female cases provided better surrogate reports than did males. Cases were better able to report for their parents and children than for their siblings. The authors conclude that when the use of surrogate reports of melanoma risk factors is unavoidable, results should be interpreted cautiously in the light of potentially high rates of misclassification. In particular, surrogate reports appear to be a comparatively poor measure of self-assessment of number of moles, the strongest known phenotypic indicator of melanoma risk, and may bias comparisons between families with and without a history of melanoma.

Australia↗

Melanocytic naevi and melanoma in survivors of childhood cancer.

There is evidence from previous studies of small numbers of children who received cytotoxic therapy for cancer, that they may develop increased numbers of melanocytic naevi (moles), the strongest known risk factors for melanoma. Our aim was to investigate a large number of survivors of childhood cancer in order to test the hypothesis that they have more melanocytic naevi than matched controls. Total-body naevus counts were obtained from 263 oncology patients ascertained in paediatric oncology departments in Queensland, Australia, and from 263 hospital controls matched for age and sex. Additional information was gathered from children's parents about concurrent factors influencing naevus development such as type of complexion and history of sun exposure. Matched analyses, both crude and adjusted for possible confounding factors, revealed no significant difference in overall density of naevi among oncology patients and control subjects, according to diagnosis or to duration or type of chemotherapy. However significantly more oncology patients had atypical naevi (P < 0.05) and acral naevi (P < 0.0001) than controls. One patient developed a malignant melanoma 13 years after chemotherapy and radiotherapy for rhabdomyosarcoma. These findings support an association between treatment for childhood cancer and acral naevi and suggest that atypical naevi may also be associated with chemotherapy in childhood.

Adolescent↗

Studies of human zinc kinetics using the stable isotope 70Zn.

1. The short-term (120 min) kinetics of Zn turnover has been studied in control subjects and patients with alcoholic liver disease after intravenous injection of 0.5 mg of 96.5% enriched 70ZnCl2. 2. The 70Zn enrichment of plasma was found closely to obey two-compartment kinetics and the derived two-component decay equation has been used to calculate the size and turnover of the initial two rapidly exchanging pools of body Zn. 3. In normal subjects isotopic Zn appears initially to equilibrate with the whole of the plasma Zn which comprises the first metabolic compartment, pool a. This has a size of 0.72 +/- 0.1 mumol/kg. 70Zn equilibration then occurs with a second compartment, pool b, consistent with a rapidly exchanging liver Zn pool of size 3.60 +/- 0.93 mumol/kg. The fractional turnover rate of pool b was found to be fivefold slower than that of pool a. 4. In the alcoholic group an expansion of pool a was observed (1.63 +/- 0.39 mumol/kg), but the size of the second pool was not significantly different from that of control subjects (5.55 +/- 1.0 mumol/kg), although its fractional turnover was significantly increased (Kab: control subjects, 0.018 +/- 0.002 min-1, alcoholic patients, 0.031 +/- 0.006 min-1). 5. These data therefore demonstrate that kinetic studies using stable isotopes of Zn can provide novel information on exchangeable Zn pools in man, but provide no support for the possibility of an underlying Zn depletion in patients with alcoholic liver disease.

Adult↗

Student selection: are the school-leaving A-level grades in biology and chemistry important?

This study determined the relationships of grades in A-level biology and chemistry with examination success or failure during the medical course. By inspection of medical student records, A-level grades at entry to medical school and examination performance were obtained for 128 (91%) of the students who sat their final MBBCh examination at the University of Wales College of Medicine in June 1988. The majority, 92 (72%), completed their medical school careers with no professional examination failures; 15 failed examinations just in the period up to 2nd MB; 11 failed examinations in the clinical period only and 10 failed examinations in both periods. Whereas grade achieved in A-level chemistry was not associated with undergraduate examination performance, students with a grade A or B in A-level biology were less likely to have problems than the others (21% compared with 47%; the difference of 26% has a 95% confidence interval of 7% to 44%). Specifically, there appears to be a strong relationship between a low grade in biology and difficulties in the preclinical examinations. Moreover, for those who have difficulties at this stage, this association continues later in the course.

Educational Measurement↗

Preclinical progress in relation to personality and academic profiles.

One hundred and forty-six (93%) of the University of Wales College of Medicine intake of new students completed a personality questionnaire (Cattell 16PF) on registration in October 1988. The students were divided into four groups depending on their academic progress up to and including 2nd MB BCh. Whereas the majority (73%) encountered no major examination problems, 40 (27%) did experience such difficulties, nine of them serious enough to delay graduation. Fourteen students had left the course, nine of them voluntarily. Academic progress was not significantly related to any of Cattell's personality factors, either primary or second order. Further analyses of established clusters of factors which have previously been associated with problems among students were also shown to be unrelated to the medical students' progress. A profile at entry involving previous degrees, points obtained and number of attempts at A-levels proved to be a much better predictor of success during the preclinical period.

Adult↗