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Biomedical subjects

R Andres

Publications and source records attributed to R Andres.

At least 37 records · Page 2Linked to original sources

Cell ashing for trace element analysis: A new approach based on ultraviolet/ozone.

We studied a new approach to cell ashing based on illuminating the specimens with a low-pressure mercury discharge lamp. We analyzed with synchrotron spectromicroscopy its effects on different physiological elements in neurobiological specimens. Our results demonstrate that carbon is removed, whereas phosphorus, calcium, potassium, and sulfur are retained and their relative concentrations are enhanced. Applied to trace elements, this technique will enhance their practical detectability.

Animals↗

Multiple roles for hepatocyte growth factor in sympathetic neuron development.

We have studied the role of hepatocyte growth factor (HGF)/Met signaling in the development of sympathetic neuroblasts and neurons. Anti-HGF antibodies reduced the number of sympathetic neuroblasts that differentiated into neurons, but neither anti-HGF antibodies nor HGF affected neuroblast proliferation. Anti-HGF antibodies also reduced the survival of neuroblasts but not sympathetic neurons. HGF greatly enhanced the neurite outgrowth of NGF-dependent sympathetic neurons throughout development. These in vitro effects of anti-HGF antibodies and HGF were abolished by a disabling mutation of Met, the HGF receptor tyrosine kinase. The Met mutation also increased sympathetic neuroblast apoptosis in vivo. Because Met and HGF are expressed in sympathetic ganglia throughout development, it is possible that the multiple effects of HGF/Met signaling on sympathetic neuroblasts and neurons occur in part by an autocrine mechanism.

Animals↗

The effect of ashing on cells: spectromicroscopy of physiological elements.

We analyzed the effects of cold oxygen plasma ashing of neurobiological specimens on different elements with synchrotron spectromicroscopy. Our results demonstrate that while carbon is almost completely removed, phosphorus, calcium, potassium, sulfur, and, to some extent, nitrogen are retained and their relative concentration is enhanced.

Animals↗

Acetylator phenotype in relation to age and gender in the Baltimore Longitudinal Study of Aging.

This study investigated in healthy Caucasians the possible occurrence of age and gender-associated differences in NAT2 acetylator phenotype. Acetylator phenotype was determined after a single oral dose of 100 mg dapsone during testing of oral glucose tolerance in 510 Caucasian volunteers aged from 19 to 93 years, 339 men and 171 women, from the Baltimore Longitudinal Study of Aging. Participants were classified as slow or rapid acetylators according to the ratio of monoacetyldapsone to dapsone concentration in plasma. The ratio dividing the two groups, 0.30, was chosen after inspection of a probit plot and histogram of the monoacetyldapsone/dapsone ratios. Fifty-one percent of the participants were slow acetylators and 49% were rapid acetylators. Because there was no significant difference between the sexes in the monoacetyl-dapsone/dapsone ratios, all 510 participants were pooled into a single group for further analysis. In the combined analysis, there was a small decline in the prevalence of the slow acetylator phenotype with age, but this age effect accounted for less than 1% of the total variance in the monoacetyldapsone/dapsone ratio (r2 = 0.009). Also, it was shown in a group of 20 participants that administration of glucose with dapsone does not influence the determination of acetylator phenotype. In a large healthy Caucasian. American population, there was no biologically important effect of age or sex on the distribution of NAT2 acetylator phenotype.

Adult↗

Biological dosimetry: the potential use of radiation-induced apoptosis in human T-lymphocytes.

An assay for biological dosimetry based on the induction of apoptosis in human T-lymphocytes is described. Radiation-induced apoptosis was assessed by flow cytometric identification of cells displaying apoptosis-associated DNA condensation. CD4 and CD8 T-lymphocytes were analysed. They were recognized on the basis of their cell-surface antigens. Four parameters were measured for both cell types: cell size, granularity, antigen immunofluorescence and DNA content. Apoptosis was quantified as the fraction of CD4-, or CD8-positive cells with a characteristic reduction of cell size and DNA content. At doses below 1 Gy, levels of radiation-induced apoptosis increased for up to 5 days after irradiation. Optimal dose discrimination was observed 4 days after irradiation, at which time the dose-response curves were linear, with a slope of 8% +/- 0.5% per 0.1 Gy. In controlled, dose-response experiments the lowest dose level at which the radiation-induced apoptosis frequency was still significantly above control was 0.05 Gy. After 5 days post-irradiation incubation, intra- and interdonor variations were measured and found to be similar; thus, apoptotic levels depend more on the dose than on the donor. The results demonstrate the potential of this assay as a biological dosimeter.

Apoptosis↗

Predictors of progression from impaired glucose tolerance to NIDDM: an analysis of six prospective studies.

Risk factors associated with the progression from impaired glucose tolerance (IGT) to NIDDM were examined in data from six prospective studies. IGT and NIDDM were defined in all studies by World Health Organization (WHO) criteria, and baseline risk factors were measured at the time of first recognition of IGT. The studies varied in size from 177 to 693 participants with IGT, and included men and women followed from 2 to 27 years after the recognition of IGT. Across the six studies, the incidence rate of NIDDM was 57.2/1,000 person-years and ranged from 35.8/1,000 to 87.3/1,000 person-years. Although baseline measures of fasting and 2-h postchallenge glucose levels were both positively associated with NIDDM incidence, incidence rates were sharply higher for those in the top quartile of fasting plasma glucose levels, but increased linearly with increasing 2-h postchallenge glucose quartiles. Incidence rates were higher among the Hispanic, Mexican-American, Pima, and Nauruan populations than among Caucasians. The effect of baseline age on NIDDM incidence rates differed among the studies; the rates did not increase or rose only slightly with increasing baseline age in three of the studies and formed an inverted U in three studies. In all studies, estimates of obesity (including BMI, waist-to-hip ratio, and waist circumference) were positively associated with NIDDM incidence. BMI was associated with NIDDM incidence independently of fasting and 2-h post challenge glucose levels in the combined analysis of all six studies and in three cohorts separately, but not in the three studies with the highest NIDDM incidence rates. Sex and family history of diabetes were generally not related to NIDDM progression. This analysis indicates that persons with IGT are at high risk and that further refinement of risk can be made by other simple measurements. The ability to identify persons at high risk of NIDDM should facilitate clinical trials in diabetes prevention.

Adolescent↗

Metabolic correlates of obesity and radiographic features of knee osteoarthritis: data from the Baltimore Longitudinal Study of Aging.

OBJECTIVE: To examine the relationship between metabolic correlates of obesity and radiographic knee osteoarthritis (OA). METHODS: We included 464 Caucasian men and 275 Caucasian women aged 40 years and above who were participants in the Baltimore Longitudinal Study of Aging. Subjects had bilateral anteroposterior standing knee radiographs read for features of OA using Kellgren-Lawrence scales. Resting blood pressure, fasting lipids, 2 h oral glucose tolerance test, and anthropometric measurements were obtained at the same visit as the knee radiograph. Metabolic correlates of obesity were compared between subjects with Kellgren-Lawrence grade > or = 2 (definite knee OA) and grade 0 (normal radiograph) by sex. RESULTS: Both men and women with knee OA had higher unadjusted systolic blood pressure than those with normal knee radiographs; unadjusted measures of glucose metabolism and lipids did not vary by presence of knee OA in men or women. After adjustment for age and obesity, systolic blood pressure did not vary by presence of knee OA in men. While women with knee OA did have higher adjusted mean systolic blood pressure than women with normal radiographs (127 +/- 2.4 vs 120 +/- 2.2 mm Hg; p = 0.04), both values were within normal range. Unexpectedly, men with knee OA had lower adjusted mean 2 h glucose levels compared to men without OA (7.5 +/- 0.2 vs 8.4 +/- 0.2 mmol/l; p = 0.01). Other adjusted variables did not differ by presence of knee OA. CONCLUSION: These data do not support the hypothesis that metabolic correlates of obesity are independently associated with radiographic knee OA after adjustment for age and obesity.

Adult↗

Insulin response during the oral glucose tolerance test: the role of age, sex, body fat and the pattern of fat distribution.

To clarify their primary roles on insulin response to oral glucose, age and sex differences in body composition should be taken into account. Oral glucose tolerance tests were performed on 472 men and 299 women of the Baltimore Longitudinal Study of Aging, ranging in age from 20 to 96 years. Subjects who were taking medications or had any diseases which could affect glucose tolerance were excluded. In addition to insulin and glucose values for the glucose tolerance test, we calculated body mass index (BMI), percentage body fat from skinfolds (% Body Fat), waist hip ratio (WHR), mean glucose level over the 2-hour test (GM), the basal insulin (IO), and the mean insulin response over the 2-hour test (IM). There was no significant sex difference in mean age, but men had significantly higher BMI (25.6 vs 24.0 kg/m2), WHR (0.93 vs 0.76), and GM (8.5 vs 7.7 mM), while % Body Fat was lower (25% vs 33%). Unadjusted IO and IM levels were significantly higher in men than in women (51 vs 44 and 303 vs 231 pM--antilogs of log-normalized values). Insulin levels, adjusted for differences in age, % Body Fat, WHR, and GM by analysis of covariance, however, showed no sex differences (49 vs 46 and 282 vs 257 pM). Adjusted insulin levels declined significantly with age; IM fell progressively from 323 pM in 20 to 39-year olds, 267 pM in 40 to 59-year, 253 pM in 60 to 79-year, and 228 pM in 80 to 96-year olds (p < 0.01). We conclude that the sex differences in insulin levels are explained by differences in body habitus and post-load glucose levels, but that insulin levels decline with age per se.

Adipose Tissue↗

The effect of age on insulin resistance and secretion: a review.

Aging is associated with an increased incidence of hypertension, noninsulin-dependent diabetes mellitus, and coronary heart disease. Because these conditions often cluster in the same individuals, there has been speculation that a common mechanism is responsible for all of these pathological states. Both epidemiological and clinical research has shown that insulin resistance and/or hyperinsulinemia are associated with glucose intolerance, dyslipidemia (high plasma triglyceride and low high-density lipoprotein-cholesterol levels), and higher systolic and diastolic blood pressures. Therefore, insulin resistance and hyperinsulinemia have been proposed as the causal link among the elements of the cluster mentioned above, now most commonly referred to as the insulin resistance syndrome, syndrome X, or the metabolic syndrome. The elderly are more glucose intolerant and insulin-resistant, but it remains controversial whether this decrease in function is an inevitable consequence of "biological aging" or the result of what might be referred to as environmental or lifestyle variables: increased obesity, a detrimental pattern of fat distribution, or physical inactivity that usually accompany age. All of these modifiable environmental factors have also been shown to result in increases in insulin resistance and hyperinsulinemia and are risk factors for the development of the diseases of the metabolic syndrome. Recent interventional studies that have attempted to reverse these conditions in the elderly have shown improved insulin sensitivity, and glucose tolerance. Insulin secretion, on the other hand, seems to decrease with age even after adjustments for differences in adiposity, fat distribution, and physical activity. This may be responsible for the glucose intolerance in the very old even after improvements have been made in their lifestyle variables.

Aging↗

Longitudinal evaluation of serum androgen levels in men with and without prostate cancer.

Androgens are thought to play a role in the pathogenesis of prostate cancer. We evaluated androgen levels in 3 age-matched groups of men who were part of the Baltimore Longitudinal Study of Aging: 1) 16 men with no prostatic disease by urologic history and exam (control group); 2) 20 men with a histologic diagnosis of benign prostatic hyperplasia (BPH) who had undergone simple prostatectomy; and 3) 20 men with a histologic diagnosis of prostate cancer (16 with local/regional cancer, and 4 with metastatic cancer). Luteinizing hormone (LH), total testosterone (T), and free T were measured on stored AM sera by radioimmunoassay (RIA). Free T was also calculated from the measured concentrations of total T and sex hormone binding globulin (SHBG). The median number of repeated sex steroid measurements ranged from 6-9 over a period from 7-25 years prior to the diagnosis of prostate disease. There were no significant differences in age-adjusted LH, total T, SHBG, or calculated free T levels among the groups at 0-5, 5-10, and 10-15 years before diagnosis. These data suggest that there are no measurable differences in serum testosterone levels among men who are destined to develop prostate cancer and those without the disease.

Age Factors↗

High plasma vitamin C associated with high plasma HDL- and HDL2 cholesterol.

High plasma vitamin C may lower risk of cardiovascular disease as indicated by direct association with plasma high-density-lipoprotein (HDL) cholesterol and HDL2 cholesterol. Plasma lipids and vitamin C were determined in 316 women and 511 men (aged 19-95 y). After adjustment for age, sex, obesity, and smoking, plasma vitamin C was directly associated with HDL- (P = 0.01) and HDL2 cholesterol (P = 0.0002). When men and women with diseases that might affect lipids were excluded, associations between plasma vitamin C and HDL- and HDL2 cholesterol persisted, though the relationships were strongest in older men. Comparisons of diets in a subset (n = 485) who completed 7-d diet records were made. Total fat, saturated fatty acids, energy from fat, and cholesterol intakes were not associated with plasma vitamin C. Mean intakes of vitamin C were well above recommended dietary allowances. These findings suggest that high plasma concentrations of vitamin C may lower atherogenic risk.

Adult↗

A direct radioimmunoassay for free progesterone in saliva.

The direct radioimmunoassay using iodinated tracer (125I-HIS-3CMO) has been developed for the determination of salivary progesterone of healthy volunteers with regular menstrual cycles. Lack of significant diurnal variation either in the follicular or luteal phase indicated that collections of saliva could be tailored to the need of individuals making the study somewhat easier. Salivary progesterone has shown to correlate significantly with free serum progesterone reflecting the unbound biologically active progesterone fraction in blood. Moreover, salivary progesterone concentration ranges are similar to those found in other studies. Our findings indicated that determination of progesterone in saliva could be used in place of serum or plasma. Since firstly, it is non-invasive, easy for sample collection and a stress-free technique. Secondly, it is much more accurate in prediction of corpus luteum function and ovulation than the basal-body temperature or endometrial biopsy or other clinical predictors currently in use. Finally, determination of daily salivary progesterone levels throughout the menstrual cycle may be advantageously employed as a non-invasive serial sampling technique for the assessment of corpus luteum and ovarian functions.

Adolescent↗

Body mass index and mortality in Seventh-day Adventist men. A critique and re-analysis.

The aim of this work was to determine if the relationship between weight-adjusted-for-height (expressed as body mass index or BMI) using the BMI-at-entry and age-at-entry as opposed to BMI at entry and age-at-event (i.e. death, loss to follow-up, or end of the study) would alter the results previously reported from a population of Seventh-day Adventist men. The subjects were 8828 non-smoking, non-drinking Seventh-day Adventist men, ages 30-89 and older on entry, mean follow-up 15 years (maximum 26 years). The BMI and age reported by subjects when they were enrolled into the study were used to calculate the relationship between BMI and mortality. Mortality rates in each of five BMI quintiles were computed by dividing the number of deaths in each quintile by the number of person years of follow-up in the quintile. Rate ratios were computed by dividing each mortality rate by the rate in the reference quintile. The mortality rate ratios were then adjusted for the age difference between each quintile and the reference quintile. Calculations based upon age-at-enrollment rather than 'age-at-event' (as used in the original paper) demonstrate no increase in mortality until a BMI of 27.5 kg/m2 or greater is reached rather than a progressive increase in mortality with increasing BMI.

Adult↗