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Biomedical subjects

H Schirmer

Publications and source records attributed to H Schirmer.

At least 19 recordsLinked to original sources

Tracking of cardiovascular risk factors: the Tromsø study, 1979-1995.

Tracking of cardiovascular risk factors (blood pressure, body mass index (BMI), and serum lipids) has not been studied much in a general, adult population. No known study has compared tracking of these factors for both sexes. In the present study, 17,710 men and women aged 20-61 years at baseline attended two or three population-based health surveys in Tromsø, Norway, over 16 years (between 1979-1980 and 1994-1995). Tracking coefficients were estimated by using different methods, and possible predictors of tracking were found. There was a high degree of tracking for BMI (overall tracking coefficients: 0.85 for men, 0.80 for women). Relatively high (or moderate) tracking was found for systolic blood pressure (respective sex-specific coefficients: 0.52, 0.54), diastolic blood pressure (0.48, 0.48), high density lipoprotein cholesterol (0.55, 0.64), and total cholesterol (0.77, 0.65). The lowest coefficients were for triglycerides (0.43, 0.39). Analysis of tracking in the upper sextile confirmed these results. Although some baseline predictors were associated with tracking, the effects were relatively weak. When predictors for tracking in the upper sextile were assessed, significant associations were found with relatively strong effects. No major sex differences were observed in tracking. However, women were more likely than men to remain in the upper sextile of systolic and diastolic blood pressures and of BMI.

Adult↗

Highly functionalized five-membered carbocycles from (3-dialkylamino-1-ethoxyalkenylidene)pentacarbonylchromium complexes and alkynes: the effects of substituents, solvents, ligand additives, and reagent concentrations on the product distribution.

The cocyclization reaction of pentacarbonyl(beta-amino-1-ethoxyalkenylidene)chromium complexes 1 with alkynes has been studied with respect to the effects of substituents, solvents, ligand additives, and reagent concentrations upon the product distribution. This reaction proceeds either as a formal [2 + 2 + 1] cycloaddition to give 5-(1'-dialkylaminoalkylidene)-4-ethoxycyclopent-2-enones 8 or a formal [3 + 2] cycloaddition to give 5-dialkylamino-3-ethoxy-1,3-cyclopentadienes 9. A working hypothesis for the mechanism of this reaction is proposed on the basis of that previously determined for the Dötz reaction. The effects of the aforementioned parameters upon the product distribution of this current reaction are explained in terms of this model. A pronounced ligand-induced allochemical effect has been observed. Conditions for the selective preparation of both classes of cycloadducts 8 and 9 have been determined.

Journal Article↗

Increase in weight in all birth cohorts in a general population: The Tromsø Study, 1974-1994.

BACKGROUND: Obesity is a risk factor for a number of chronic diseases. Few longitudinal studies have examined changes in body mass index (BMI [calculated as weight in kilograms divided by the square of the height in meters]). OBJECTIVE: To investigate the changes in mean BMI and the prevalence of obesity in a large cohort examined several times during a 20-year period. METHODS: Mean BMI, the percentage of subjects with low BMI (<20 kg/m(2)), and the percentage who were obese (BMI > or =30 kg/m(2)) were determined in a large population of men and women who were examined up to 4 times during a 20-year period (1974-1994/1995). In a longitudinal design, we observed 3541 men who attended all 4 screenings (1974-1994/1995) and 4993 women who attended the last 3 screenings (1979/1980-1994/1995). RESULTS: The age- (25-49 years) and sex-adjusted mean BMI increased 1 kg/m(2) in men from 1974 to 1994/1995 and 0.9 kg/m(2)in women from 1979/1980 to 1994/1995. In the last survey, subjects aged 25 to 85 years were included. In most age groups, the mean BMI exceeded 25 kg/m(2) and the prevalence of obesity was 10% or higher in men and women aged 45 years or older. In the longitudinal analysis, the mean BMI in men aged 20 to 49 years increased 2.0 kg/m(2) during 20 years of observation and increased 2.4 kg/m(2)in women aged 20 to 49 years during 15 years of observation. The increase in BMI was larger in younger men than in older men. CONCLUSIONS: Body mass index increased in every examined birth cohort (1925-1964) during the 15- to 20-year observation period. Primary prevention of further increased body weight should be a priority.

Adult↗

Fischer Carbene Complexes as Chemical Multitalents: The Incredible Range of Products from Carbenepentacarbonylmetal alpha,beta-Unsaturated Complexes.

The metal carbene complexes, discovered by E. O. Fischer at the start of the 1960s and carrying his name, have since proved themselves to be irreplaceable building blocks for organic synthesis. In particular, since the discovery of the Dötz reaction, a formal cycloaddition of Fischer alpha,beta-unsaturated carbene complexes to alkynes with CO insertion, this area of chemistry has become increasingly interesting to organic chemists. In spite of the considerable diversity of reactions performed with these complexes, proper selection of substrates and careful adjustment of the reaction conditions have allowed, in most cases the perfectly selective preparation of individual compounds of this enormous range of products. The spectrum of new successes begins with the conventional Diels-Alder reaction of alkynylcarbene complexes and the formal regioselective [3+2] cycloaddition of alkenylcarbene complexes to alkynes. It extends much further, however, from cascade reactions with the formation of oligofunctional and oligocyclic products of impressive molecular complexity to complex, formal [3+6] cocyclizations in which six bonds are formed in a single operational step. Beyond doubt, the methodological arsenal of preparative organic chemistry cannot be imagined any more without the valuable transformations of the Fischer carbene complexes; it only remains to be seen whether one or other of the numerous new types of cocyclization products of these complexes can establish itself as a lead structure in the search for biologically active compounds.

Journal Article↗

Impact of body weight on blood pressure with a focus on sex differences: the Tromso Study, 1986-1995.

BACKGROUND: The prevalence of obesity and hypertension is increasing in Western societies. We examined the effects of initial body mass index ([BMI] weight in kilograms divided by height in meters squared) and change in BMI on change in blood pressure, and we assessed sex differences. METHODS: A general population in the municipality of Tromso, northern Norway, was examined in 1986 and 1987 and again in 1994 and 1995. Altogether, 75% of the individuals, women aged 20 to 56 years and men aged 20 to 61 years, attended the baseline examination. A total of 15,624 individuals (87% of all still living in the municipality) were examined twice. RESULTS: Mean BMI increased between the examinations, more for the younger than the older examinees, and also more among women than men (P<.001). Adjusted for several covariates, BMI change was associated with systolic and diastolic blood pressure change for both sexes (regression coefficients: 1.43 [95% confidence interval (CI), 1.23-1. 64] and 0.90 [95% CI, 0.76-1.04], respectively, for men; and 1.24 [95% CI, 1.09-1.39] and 0.74 [95% CI, 0.63-0.84] for women). Baseline BMI was associated with systolic and diastolic blood pressure change for women only (regression coefficients: 0.38 [95% CI, 0.30-0.47] and 0.17 [95% CI, 0.11-0.23], respectively). CONCLUSIONS: For women, both BMI at baseline and BMI change were independently associated with blood pressure change. For a given increase in BMI, obese women had a greater increase in blood pressure than lean women. This was not the case for men, for whom BMI change was the only significant predictor. Furthermore, a BMI increase for obese women induced a greater systolic blood pressure increase compared with men.

Adult↗

Mitral flow derived Doppler indices of left ventricular diastolic function in a general population; the Tromso study.

AIMS: Left ventricular diastolic dysfunction has been proposed as the basis of heart failure in patients with normal left ventricular systolic function. Doppler indices of mitral inflow have been widely used to diagnose this condition and have been shown to correlate well with increased left atrial pressure in patients with cardiovascular disease. We wanted to establish age-specific criteria for normality of these indices in a large population and to determine the association of abnormal values to age and cardiovascular disease. METHODS AND RESULTS: In our sample of subjects aged 25-85 years, 3022 had pulsed Doppler measurements of mitral inflow velocities and early inflow deceleration time. The association of these indices to age and gender were established in a 'healthy' reference subsample of 949 subjects. Age-specific percentiles showed a significant decline with increasing age for peak early mitral inflow velocity and the ratio of peak early and atrial inflow velocities (E/A ratio), whereas early inflow deceleration time and peak atrial inflow velocity showed a significant increase with increasing age. According to current criteria for diastolic dysfunction, the prevalence of dysfunction decreases with increasing age in the general population, as well as in the subgroup with cardiovascular disease. Only 7% of the variance in deceleration time was explained by cardiovascular disease or risk factors. For the E/A ratio, however, 41 and 48% of the variance were explained for men and women, respectively. CONCLUSION: Age- and gender-specific criteria for normality are provided. Our data confirm the existence of a significant effect of age and gender on mitral Doppler indices of diastolic dysfunction. However, Doppler criteria for diastolic dysfunction based on these measurements need revision.

Adult↗

What determines echogenicity in a general population? The Tromsø Study.

BACKGROUND: It is widely recognized that in some people it is difficult or impossible to acquire adequate measurements of cardiac performance and anatomy by any echocardiographic technique. We used our population-based screening to determine the characteristics of such unmeasurable subjects. METHOD: In a sample of 3287 subjects aged 25 to 85 years, we used standard 2-dimensional guided M-mode echocardiography and pulsed and color Doppler to assess left ventricular (LV) structure and function. RESULTS: Of 3287 subjects only 0.4% could not be measured by any technique. In 2794 subjects M-mode registrations of good quality were obtained, which allowed calculation of LV mass and LV ejection fraction. Those in whom measurements could not be obtained had a significantly higher age, body mass index, blood pressure, waist/hip ratio, and were more likely to smoke, be a man, be taking antihypertensive medication, have a history of ischemic heart disease, and have a low level of physical activity. CONCLUSION: Because subjects with high cardiovascular risk factor levels are less likely to be measurable with echocardiography, a need exists for other noninvasive diagnostic methods in these persons.

Adult↗

Prevalence of left ventricular hypertrophy in a general population; The Tromsø Study.

AIMS: Left ventricular hypertrophy has been shown to be an independent predictor of cardiovascular morbidity. Acknowledging the skewed distribution of left ventricular mass, we wanted to develop criteria for left ventricular hypertrophy based on percentiles of left ventricular mass, and observe the effect on estimates of left ventricular hypertrophy prevalences in different subgroups and on the relationship to cardiovascular risk factors in a general population. METHODS AND RESULTS: In a population-based sample of 3287 subjects aged 25-85 years, left ventricular mass was estimated using M-mode echocardiography. A 'healthy' subgroup was used as a reference sample to define sex-specific left ventricular hypertrophy criteria. Sex-specific 97.5 percentiles for left ventricular mass by height, based on the reference sample, were 145.5 and 125.4 g.m(-1), for men and women, respectively. The prevalences of left ventricular hypertrophy in the total population were 14.9% for men and 9.1% for women. The main independent predictors of left ventricular hypertrophy were male gender, body mass index, systolic blood pressure, valvular heart disease, cardiovascular disease and antihypertensive medication. Body mass index and systolic blood pressure had a strong synergistic association with left ventricular hypertrophy in men, but not in women. CONCLUSION: An alternative framework for defining left ventricular hypertrophy is provided. Body mass index is the culprit factor for risk of left ventricular hypertrophy. Our study indicates that weight reduction is a relevant measure for treatment and possibly prevention of left ventricular hypertrophy in a substantial part of the general population.

Adult↗

Circulating N-terminal pro-atrial natriuretic peptide is an independent predictor of left ventricular hypertrophy in the general population. The Tromsø Study.

PURPOSE: The purpose of this study was to determine whether circulating N-terminal pro-atrial natriuretic peptide (N-ANP) levels predict left ventricular hypertrophy in the general population after adjustment for relevant risk factors. METHODS AND RESULTS: In a population-based sample of 3287 subjects aged 25-85 years, circulating N-ANP was measured in a subgroup of 389 subjects. Left ventricular mass and ejection fraction were determined by two-dimensional guided M-mode echocardiography. Left ventricular hypertrophy was defined as height adjusted mass above 145.5 g. m-1 and 125.4 g. m-1, in men and women, respectively. Fifty-one subjects with left ventricular hypertrophy had significantly higher N-ANP levels than controls (1075 vs 763 pmol. l-1;P<0.0001). A gradually increasing prevalence of left ventricular hypertrophy over increasing 500 pmol. l-1 intervals of N-ANP was observed (1.8 to 64. 3%; (Chi-squared P for trend <0.001). N-ANP was an independent predictor of left ventricular hypertrophy after adjustment for ejection fraction, body mass index, hypertension, valvular disease, a history of myocardial infarction, gender, and age. The adjusted odds ratio for left ventricular hypertrophy was 1.79 (95% CI 1.04-3. 07) for a 500 pmol. l-1 increase in N-ANP. A substantial proportion of subjects with elevated N-ANP levels had combined left ventricular hypertrophy and left ventricular dysfunction. CONCLUSION: These results suggests that N-ANP is an independent predictor of left ventricular hypertrophy in the general population. N-ANP determination is, however, poorly suited to distinguish between subjects with isolated left ventricular hypertrophy and left ventricular dysfunction with or without left ventricular hypertrophy.

Adult↗

Immunolocalization of glutathione reductase in the murine brain.

Free radical species arise from the univalent reduction of oxygen. The cytosolic agent H2O2, produced during enzymatic scavenging of the superoxide radical (O2-) is in turn removed predominantly via the oxidation of reduced glutathione (GSH) to the oxidized form (GSSG) by glutathione peroxidase. Subsequently GSSG is recycled back to GSH by glutathione reductase (GSH-red). Little is known about the distribution of this enzyme in the brain. The aim of this study was to determine the distribution of this enzyme in the brain of different murine species by means of immunocytochemical techniques, although most attention was given to the distribution of GSH-red in the forebrain. In most brain areas GSH-red positive neurons were detected, but the regional intracellular staining intensity differed markedly. The pre-piriform and piriform cortices, the pyramidal cell layers of the hippocampus, and the dentate gyrus were heavily stained. The caudate nucleus displayed a progressive increase in the intracellular staining intensity from the rostral to the caudolateral parts. Furthermore, in the thalamus, there was a gradual decrease in GSH-red staining from the medial to the lateral parts. The mesencephalon was poor in immunopositive cells, and in the substantia nigra pars reticulata, almost no labeling was detected. However, the substantia nigra pars compacta showed an intense GSH-red immunoreactivity. The results show a specific localization of glutathione reductase in distinct brain regions, suggesting a variable potency of different brain areas in dealing with the damaging oxidative actions of free radicals. Also, differential GSH-red expression patterns were found in the various murine species. Some species showed a pronounced GSH-red immunoreactivity in glial cells, specifically in regions that lacked neuronal GSH-red immunoreactivity.

Animals↗

Cloning, sequencing and functional overexpression of the Streptococcus equisimilis H46A gapC gene encoding a glyceraldehyde-3-phosphate dehydrogenase that also functions as a plasmin(ogen)-binding protein. Purification and biochemical characterization of the protein.

We previously identified DNA sequences involved in the function of the complex promoter of the streptokinase gene from Streptococcus equisimilis H46A, a human serogroup C strain known to express this gene at a high level. As a prerequisite to understanding possible mechanisms that control the balance between the plasminogen activating and plasmin(ogen) binding capacities of H46A, we describe here its gapC gene encoding glyceraldehyde-3-phosphate dehydrogenase (GraP-DH, EC 1.2.1.12), a glycolytic enzyme apparently transported to the cell surface where it functions as a plasmin(ogen).binding protein. The gapC gene was cloned and sequenced and found to code for a 336-amino-acid polypeptide (approximately 35.9 kDa) exhibiting 94.9% sequence identity to the Plr protein from Streptococcus pyogenes shown by others to be capable of plasmin binding [Lottenberg, R., Broder, C. C., Boyle, M. D., Kain, S. J., Schroeder, B. L. & Curtiss, R. III (1992) J. Bacteriol. 174, 5204-5210]. To study the properties of the GapC protein, its gene was inducibly overexpressed in Escherichia coli from QIAexpress expression plasmids to yield the authentic GapC or (His)6GapC carrying a hexahistidyl N-terminus to permit affinity purification. Both proteins were functionally active, exhibiting specific GraP-DH activities of about 80 kat/mol (approximately 130 U/mg) after purification. Their binding parameters [association (ka) and dissociation (kd) rate constants, and equlibrium dissociation constants (Kd = kd/ka)] for the interaction with human Gluplasminogen and plasmin were determined by real-time biospecific interaction analysis using the Pharmacia BIAcore instrument. For comparative purposes, the commercial GraP-DH from Bacillus stearothermophilus (BstGraP-DH), a nonpathogenic organism, was included in these experiments. The Kd values for binding of plasminogen to GapC, (His)6GapC and BstGraP-DH were 220 nM, 260 nM and 520 nM, respectively, as compared to 25 nM, 17 nM and 98 nM, respectively, for the binding to plasmin. These data show that both the zymogen and active enzyme possess low-affinity binding sites for the gapC gene product and that the hexahistidyl terminus does not affect its function. Prior limited treatment with plasmin enhanced the subsequent plasminogen binding capacity of all three GraP-DHs, presumably by the exposure of new C-terminal lysine residues for binding to the zymogen.

Amino Acid Sequence↗

The Svalbard study 1988-89: a unique setting for validation of self-reported alcohol consumption.

The Norwegian island of Spitzbergen, Svalbard offers a unique setting for validation studies on self-reported alcohol consumption. No counterfeit production or illegal import exists, thus making complete registration of all sources of alcohol possible. In this study we recorded sales from all agencies selling alcohol on Svalbard over a 2-month period in 1988. During the same period all adults living permanently on Svalbard were invited to take part in a health screening. As part of the screening a self-administered questionnaire on alcohol consumption was introduced to the participants. We found that the self-reported volume accounted for approximately 40 percent of the sales volume. Because of the unique situation applying to Svalbard, the estimate made in this study is believed to be more reliable compared to other studies using sales volume to validate self-reports.

Adolescent↗

New alcohol markers--how useful are they in population studies: the Svalbard Study 1988-89.

Regular high consumption of alcohol in selected populations have, with high precision, been identified by two new alcohol markers; carbohydrate-deficient transferrin and mitochondrial aspartate aminotransferase. To test these markers in an unselected population, gamma-glutamyltransferase (GGT), carbohydrate-deficient transferrin (CDT), and mitochondrial aspartate aminotransferase (mAST) were measured in the Norwegian population, 310 males and 171 females, aged 18 to 60 years, living at Svalbard. Using self-reported alcohol intake as gold standard, sensitivity, specificity, positive predictive value, and likelihood-ratio were estimated according to different cutoff-points for alcohol intake and for the tests. In contrast to earlier studies, the sensitivity was in general low. With a specificity of 90% or higher, the sensitivity did not exceed 26% for any of the tests. Whereas CDT showed its best discriminatory power at lower intake of alcohol, GGT discriminated best at higher levels. Parallel and serial analysis of CDT and GGT indicated a conditional independence between the tests, as well as at higher and at lower levels of alcohol consumption. mAST was judged as not suitable in population studies.

Adolescent↗