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Biomedical subjects

J Head

Publications and source records attributed to J Head.

At least 55 records · Page 3Linked to original sources

Determination of aromatase cytochrome P450 messenger ribonucleic acid in human breast tissue by competitive polymerase chain reaction amplification.

Local production of estrogen in breast tissue may influence the growth of breast cancers. Peripheral conversion of C19 steroids to estrogens is catalyzed by the aromatase enzyme complex which is comprised of a specific form of cytochrome P450, aromatase cytochrome P450 (P450AROM) and the flavoprotein, NADPH-cytochrome P450 reductase. To evaluate P450AROM mRNA levels in breast tissue, a specific competitive polymerase chain reaction amplification procedure was devised. In this method, a rat P450AROM complementary RNA is coamplified as an internal standard in order to compare amplification reactions. The amplification products are recognized by hybridization with 32P-labeled oligonucleotides specific for each species. Densitometry is used to quantitate autoradiographs. Initial studies using RNA from whole breast tissue obtained from reduction mammoplasty revealed linearity of the relationship between the densitometer signal from the human amplification product and total RNA concentration. Breast tissue was then separated into a floating adipocyte fraction and a pelleted fraction containing the other cellular elements by collagenase digestion and centrifugation. Comparison of specific content of aromatase amplification product per unit weight of RNA extracted from adipocytes and pelleted cells revealed considerably higher levels in the RNA from the nonadipocyte fraction. Immunocytochemical characterization of this fraction revealed the presence of several cell types including macrophages, ductal epithelial cells, and endothelial cells, but primary cells of stromal origin.

Animals↗

Health inequalities among British civil servants: the Whitehall II study.

The Whitehall study of British civil servants begun in 1967, showed a steep inverse association between social class, as assessed by grade of employment, and mortality from a wide range of diseases. Between 1985 and 1988 we investigated the degree and causes of the social gradient in morbidity in a new cohort of 10,314 civil servants (6900 men, 3414 women) aged 35-55 (the Whitehall II study). Participants were asked to answer a self-administered questionnaire and attend a screening examination. In the 20 years separating the two studies there has been no diminution in social class difference in morbidity: we found an inverse association between employment grade and prevalence of angina, electrocardiogram evidence of ischaemia, and symptoms of chronic bronchitis. Self-perceived health status and symptoms were worse in subjects in lower status jobs. There were clear employment-grade differences in health-risk behaviours including smoking, diet, and exercise, in economic circumstances, in possible effects of early-life environment as reflected by height, in social circumstances at work (eg, monotonous work characterised by low control and low satisfaction), and in social supports. Healthy behaviours should be encouraged across the whole of society; more attention should be paid to the social environments, job design, and the consequences of income inequality.

Adult↗

Results of TV imaging of Phobos (Experiment VSK-Fregat).

From February to March 1989 the Phobos 2 spacecraft took 37 TV images of Phobos at a distance of 190-1100 km. These images complement Mariner-9 and Viking data by providing higher-resolution coverage of a large region West of the crater Stickney (40-160 degrees W) and by providing disk-resolved measurements of surface brightness at a greater range of wavelengths and additional phase angles. These images have supported updated mapping and characterization of large craters and grooves, and have provided additional observations of craters' and grooves' bright rims. Variations in surface visible/near-infrared color ratio of almost a factor of 2 have been recognized; these variations appear to be associated with the ejecta of specific large impact craters. Updated determinations of satellite mass and volume allow calculation of a more accurate value of bulk density, 1.90 +/- 0.1 g cm-3. This is significantly lower than the density of meteoritic analogs to Phobos' surface, suggesting a porous interior perhaps containing interstitial ice.

Astronomy↗

A prospective study of mortality among middle-aged diabetic patients (the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics) I: Causes and death rates.

The 497 members of the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics have been followed for mortality from 1975 to 1987. During this period 92 patients died. The most common cause of death was myocardial infarction: 36 (39.1%) deaths, heart disease was responsible for 51.1% of deaths and all cardiovascular disease for 55.4%. Neoplastic disease accounted for 25% of the deaths and diabetic nephropathy for 5.4%. Age-standardised mortality rates were higher in men than in women in both Type 1 (insulin-dependent) diabetes and Type 2 (non-insulin-dependent) diabetes. Standardised mortality ratios for the first and second five year follow-up periods were higher for men than for women in Type 2 diabetes but were higher for women than men in Type 1. The results suggest that the female survival advantage seen in the general population may persist in Type 2 but not in Type 1 diabetes.

Adult↗

A prospective study of mortality among middle-aged diabetic patients (the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics) II: Associated risk factors.

Potential risk factors have been examined for association with mortality over a 10-12 year follow-up of the patients of the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics (aged 35-54 years at entry to the study). Proteinuria has the strongest association with all-cause mortality in univariate analysis being significant in patients of both sexes with Type 2 (non-insulin-dependent) diabetes mellitus and in women with Type 1 (insulin-dependent) diabetes mellitus; both systolic blood pressure (men) and hypertension (both sexes) (as a categorical variable) are significant in Type 1 diabetes. Hypertension is also significantly associated with all-cause mortality in multivariate analysis in both sexes with Type 1 diabetes as proteinuria is in women with Type 2 diabetes. There is an unexpected negative association between plasma creatinine and all-cause mortality in men with Type 2 diabetes. Systolic blood pressure and hypertension are also significantly linked with cardiovascular mortality in Type 1 diabetes, hypertension having an estimated relative risk of 4.6 [corrected] in multivariate analysis. Serum cholesterol and proteinuria showed the strongest associations with cardiovascular mortality in Type 2 diabetes. Proteinuria is associated with non-cardiovascular mortality in both types of diabetes in univariate but not multivariate analysis. In multivariate analysis hypertension (Type 1 diabetes) and diabetes duration (Type 2 diabetes) are associated with non-cardiovascular mortality. Hypertension and proteinuria have the most consistent associations with mortality in the different analyses with the effect of hypertension appearing stronger in Type 1 diabetes and proteinuria in Type 2 diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

International variations in mortality among diabetic patients: the WHO Multinational Study of Vascular Disease in Diabetics.

Mortality among 4740 diabetic men and women aged 35-55 years participating in the WHO Multinational Study of Vascular Disease in Diabetics has been studied. Ten of the original centres (Warsaw, Berlin, Havana, Arizona, Oklahoma, Hong Kong, Switzerland, London, Tokyo, Zagreb) were able to identify the life/death status of their study participants on 1 January 1983, giving an average follow-up period of six to seven years. All-cause mortality rates in males varied about threefold among the ten participating centres with the highest rates in Warsaw, Berlin and Havana and the lowest rates in Tokyo and Zagreb. All-cause mortality rates for females varied about fourfold with the highest rates in Warsaw and Oklahoma and the lowest rates in Tokyo. The proportion of deaths ascribed to circulatory disease varied among the centres ranging from 32% for males and 0% for females in Tokyo to 67% for males and 47% for females in London. There was an excess all-cause mortality in males compared to females for all centres except Zagreb. This excess also applied to circulatory diseases in general, ischaemic heart disease in particular and occurred in both insulin-dependent and non-insulin-dependent diabetic patients. Death rates for insulin-dependent diabetic patients were generally higher than those for non-insulin-dependent patients.

Coronary Disease↗

Blood pressure, proteinuria and their relationship with circulatory mortality: the WHO Multinational Study of Vascular Disease in Diabetics.

A study has been made of hypertension and its associated vascular risk in 2319 male and 2412 female participants in the WHO Multinational Study of Vascular Disease in Diabetics. Rates of hypertension were higher in non insulin-dependent diabetics (NIDDs) compared with insulin-dependent diabetics (IDDs). On average, diastolic blood pressures were lower in IDDs than NIDDs. The frequency of isolated systolic hypertension varied between 2.5% and 5.6%. In a 6 to 7 year mortality follow-up, hypertension was significantly associated with an increased risk of circulatory death, even allowing for its association with proteinuria.

Adult↗

Equilibrium and rapid kinetic studies on nocodazole-tubulin interaction.

The interaction between nocodazole and calf brain tubulin in 10(-2) M sodium phosphate, 10(-4) M GTP, and 12% (v/v) dimethyl sulfoxide at pH 7.0 was studied. The number of binding sites for nocodazole was shown to be one per tubulin monomer of 50,000 as a result of equilibrium binding studies by gel filtration and spectroscopic techniques. The presence of microtubule-associated proteins did not significantly affect the binding of nocodazole to tubulin. The apparent equilibrium constant measured at 25 degrees C was (4 +/- 1) X 10(5) M-1. Temperature does not significantly affect the apparent equilibrium constant; hence, the binding of nocodazole to tubulin is apparently entropy driven. Stopped flow spectroscopy was employed to monitor the rate of nocodazole binding under pseudo first order conditions. The effects of temperature and nocodazole concentration were studied. The apparent rate constants were dependent on the concentration of nocodazole in a nonlinear manner. In conjunction with results from structural and thermodynamic studies the kinetic results were interpreted to suggest a mechanism of T + N in equilibrium with TN in equilibrium with T* N, where T and N are tubulin and nocodazole, respectively. T and T* represent two conformational states of tubulin. Furthermore, the kinetic data are consistent with the thermodynamic data only if a model of two parallel similar reactions were considered, one rapid and the other slow. The initial binding step for both the rapid and slow phases was characterized by identical binding constants; however, there was a significant difference in the rates of isomerization. Hence, nocodazole is potentially a useful probe for amplifying differences in solution properties of tubulin subspecies.

Animals↗

On the mechanics of mucociliary flows. III. Flow-velocity profiles in frog palate mucus.

Flow-velocity profiles over excised frog ciliated epithelium were obtained for the region within about 600 micron of the mucosa. Fluorescent particles were used as flow tracers. Both a control and an autologous mucus suspension were observed. The control culture medium was bounded by the walls of the observation chamber, and mucus was deposited on the epithelium as a blob after mixing it with tracers. In spite of the difference in boundary conditions the two profiles, normalized to maximum particle velocity and solution depth, were indistinguishable at heights over 60 micron from the mucosa. The near-mucosa profiles in contrast were unalike with mucus exhibiting a greater shear gradient than the control culture medium. It was concluded that ciliary contact is not necessary for generation of mucus flow provided the ciliary shear is not negated by the mucus "flake" or "slab" being in simultaneous contact with significant ciliostatic patches which would act as anchors.

Animals↗

Observations on the response of human spermatozoa to gravity, boundaries and fluid shear.

Human sperm motility response to three mechanical stimuli, gravity, fluid flow shear and rigid boundaries, was measured in a tube of 310 X 400 microns calibre. Data were gathered by cine recordings at various focussing levels d across the tube and analysed with a computerized image analysis system. The most influential stimulus was the tube wall near (more than 'at') which the swimmers tended to accumulate, leaving the fluid beyond 100 microns from the wall (d = 100) vacant of motile spermatozoa. The boundary effect was evident as soon as the spermatozoa could be viewed after loading, and accumulation, measured as frequency, as a function of d did not change with time t. This response was not significantly altered by the addition of laminar flow with a centre line velocity of about 400 microns/sec. In flow shear, spermatozoa aligned positively (in the flow direction) at the wall but negatively by about 30 microns from the wall where the velocity gradient (= shear rate) was about 3.5 sec-1. The response to gravity was relatively weak with 11 spermatozoa positive (swimming downwards) for each 9 negative. Neither the boundary effect nor the 'rheotaxic' effect were influenced by gravity as there was no statistical difference in orientation or distribution patterns between vertically and horizontally flowing suspensions. It is suggested that the boundary effect cannot be ignored in in-vitro manipulations, particularly when spermatozoa are observed or extracted. Its importance in vivo lies in the degree to which the tubes transporting motile spermatozoa seem to have mechanisms for reversing the wall accumulation tendency.

Computers↗

Influence of lipopolysaccharide and protein in the cell envelope on recipient capacity in conjugation of Salmonella typhimurium.

In crosses of Salmonella typhimurium FfinP301 lac+ to F- strains of S. typhimurium in broth, recipient strains which were rough mutants affected in the outer core region of the lipopolysaccharide gave an average of 1.4 Lac+ transconjugants per donor cell and over 50% of the donor and recipient cells in mating aggregates, whereas smooth recipient strains gave 0.08 Lac+ transconjugants and few cells in mating aggregates. Strains with mutations affecting the inner core of the lipopolysaccharide were usually poor recipients. When cells were mated on Millipore membrane filters, both smooth and rough strains gave ca. 1.0 Lac+ transconjugants per donor cell. Plasmids in Inc groups FI, FII, M, J, and I beta gave more transconjugants with rough than smooth strains, but there were no difference in crosses with plasmids in Inc groups T, L, P, N, and W. Strains with mutations in the ompA gene (deficient in Omp Ap = 33K = II* = conjugation protein) yielded only 0.02 Lac+ transconjugants per donor cell and few cells in mating aggregates. There was no indication of a deficiency of Omp Ap in smooth strains compared with rough strains. Reduced fertility of smooth recipients may occur because the O side chains of the lipopolysaccharide shield the recipient and reduce the frequency of stabilization of mating aggregates. However, gradient-of-transmission experiments indicated that once these mating aggregates are stabilized, they are equally stable in both smooth and rough recipients. Fertility was high in crosses of S. typhimurium Flac+ to Escherichia coli K-12 F- (0.75 Lac+ transconjugants per donor cell; over 50% of the cells in mating aggregates). In crosses of E. coli K-12 Flac+ to S. typhimurium smooth F-, ca. 10(-5) Lac+ transconjugants per donor cell were obtained; in crosses to rough recipient strains, fertility was increased 14-fold, and when the recipient was defective in the SA and LT host restriction systems, fertility was increased in additional 100-fold. Thus, both the lipopolysaccharide and the protein in the cell envelope of S. typhimurium were shown to be important in the recipient function in F-mediated conjugation.

Bacterial Proteins↗

The radiologic appearance of chemical pleurodesis.

Intrapleural instillation of drugs (chemical pleurodesis) was performed in 57 patients with malignant pleural effusions or recurrent pneumothorax. Agents used included mechlorethamine hydrochloride (nitrogen mustard), quinacrine hydrochloride (Atabrine), tetracycline, and others. The most frequent finding on chest radiographs (56%) was multiple loculated air-fluid levels, an appearance simulating an empyema. Resolution of these changes occurred in one to three weeks. Late sequelae included pleural thickening (63%) or the development of a severe fibrothorax. In the majority of the six patients treated for recurrent pneumothoraces, the radiographic appearance returned to normal. The appearance of a new air-fluid level following withdrawal of the chest tube in one patient indicated a complicating empyema.

Adolescent↗

Effects of estradiol and prolactin on growth of rat mammary adenocarcinoma cells in monolayer cultures.

The effects of estradiol and ovine prolactin on the growth of a rat mammary adenocarcinoma cell line were investigated. The action of estradiol was dose-dependent. At less than or equal to 1 mug/ml it did not influence growth, at 5-10 mug/ml it was inhibitory, and at 20 mug/ml it was toxic. Prolactin alone had little effect on growth. However, the inhibitory effect of estradiol could be counteracted by a high concentration of prolactin. It appears, therefore, that the growth of cultured rat mammary adenocarcinoma cells can be regulated by the ratio of prolactin to estradiol: When the ratio is high growth is favored; when it is low, growth is inhibited.

Adenocarcinoma↗