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Biomedical subjects

B Rosenberg

Publications and source records attributed to B Rosenberg.

At least 19 recordsLinked to original sources
PubMed1997

Interference with microtubules and induction of micronuclei in vitro by various bisphenols.

Bisphenols, in particular bisphenol-A (BP-A), are monomers of various plastics including polycarbonates and epoxy resins which are used in numerous consumer products. The release of BP-A from some of these materials has recently been reported. BP-A is a weak estrogen and structurally related to the aneuploidogenic stilbene estrogen diethylstilbestrol (DES). We have therefore studied BP-A and four other bisphenols for their aneuploidogenic potential by assaying their (i) interference with the cell-free assembly of microtubules (MT); (ii) disruption of the cytoplasmic MT complex in cultured Chinese hamster V79 cells; (iii) disruption of the mitotic spindle and induction of metaphase arrest in V79 cells; and (iv) induction of micronuclei (MN) in V79 cells. At concentrations without gross cytotoxicity, BP-A as well as its alkyl-fluorinated and ring-methylated analog were active at all endpoints tested, whereas the bisphenol without alkyl groups was completely inactive. 4,4'-Dihydroxybenzophenone was inactive against cell-free and cytoplasmic MT but disrupted the mitotic spindle and induced metaphase arrest and MN. The MN caused by the various bisphenols were analyzed for the presence of kinetochores by staining with CREST antibodies. All induced MN were CREST-positive, implying that they contain whole chromosomes/chromatids. The effects on MT and the induction of metaphase arrest and of CREST-positive MN suggest that the environmental estrogen BP-A and some of its analogs are potential aneuploidogens.

Aneuploidy↗
PubMed1997

Time series analysis supporting the hypothesis that enhanced cosmic radiation during germ cell formation can increase breast cancer mortality in germ cell cohorts.

Techniques from cancer epidemiology and time series analysis were used to explore the hypothesis that cosmic radiation can induce germ cell changes leading to increases in future breast cancer mortality. A birth cohort time series for female breast cancer mortality was obtained using a model-independent, age-period-cohort analysis on age-specific mortality data for 1940-1990. The birth cohort series contained several oscillatory components, which were isolated and compared to the corresponding frequency components of a cosmic ray surrogate time series-Greenland ice-core 10Be concentrations. A technique, referred to as component wave-train alignment, was used to show that the breast cancer and cosmic ray oscillations were phase-locked approx. 25 years before the time of birth. This is consistent with the time of germ cell formation, which occurs during the fetal development stage of the preceding generation. Evidence is presented that the observable oscillations in the birth cohort series were residues of oscillations of much larger amplitude in the germ cell cohort, which were attenuated by the effect of the broad maternal age distribution. It is predicted that a minimum of 50% of breast cancer risk is associated with germ cell damage by cosmic radiation (priming event), which leads to the development of individuals with a higher risk of breast cancer. It is proposed that the priming event, by preceding other steps of carcinogenesis, works in concert with risk factor exposure during life. The priming event is consistent with epigenetic changes such as imprinting.

Adult↗
PubMed1997

Comparative psychophysical characteristics of cutaneous CO2 laser and contact heat stimulation.

Psychophysical visual analog scaling can be used to reveal critical determinants of the neural processing underlying non-painful and painful heat sensations produced by radiant and contact heat stimulation. This study determined the stimulus-response (S-R) functions of cutaneous non-painful and painful heat stimuli delivered by an infra-red CO2 laser or by a contact thermode in a series of experiments in healthy volunteers. In experiments 1 (n = 12), with the rating scale anchored at pain threshold, the S-R curve for brief (60 ms) laser pulse stimulation with a beam diameter of 10 mm was a negatively accelerating function. Transformation of laser stimulus intensity (W) into temperatures (degree C) did not change the form of the S-R curve. In experiment 2 (n = 9), using the same laser stimulus parameters as in experiment 1, but without an anchored rating scale, the form of the S-R relationship did not change. In experiment 3 (n = 9), increases of the laser pulse duration up to 5 s and the beam diameter up to 18 mm produced linear S-R curves. In contrast, in experiment 4 (n = 21), the S-R curve for cutaneous contact heat stimuli applied for 5 s with an 18 mm diameter probe was best described by a positively accelerating power function with an exponent greater than 2.0. These experiments have (1) characterized the S-R functions for different parameters of infra-red laser stimulation of the skin, and (2) have shown that the form of the S-R function for innocuous and noxious heat sensation is influenced strongly by the physical conditions of heat stimulus application, including mechanical contact with the skin.

Adolescent↗
PubMed1997

The Oil, Chemical, and Atomic Workers International Union: refining strategies for labor.

In a period of declining union membership and severe economic and environmental crisis it is important that labor unions rethink their traditional roles and organizational goals. Responding to some of these problems and reflecting a history of innovative and progressive unionism, the Oil, Chemical and Atomic Workers Union (OCAW) has sought to address occupational and environmental health problems within the context of a political struggle. This study suggests that by joining with the environmental movement and community activists, by pursuing a strategy of coalition building, and by developing an initiative to build and advocate for a new political party, OCAW provides a model for reinvigorating trade unionism in the United States.

Chemical Industry↗
PubMed1994

[Pulmonary alveolar proteinosis].

Pulmonary alveolar proteinosis is a rare disease of unknown etiology characterized by alveoli filled with PAS-positive material high in protein and lipid. A 30-year-old man was referred because of respiratory failure. 2 years previously exertional dyspnea and productive cough appeared and gradually worsened. A year later he sought medical advice but defaulted on follow-up. After further deterioration he returned for treatment. On examination he had tachypnea and cyanosis. Diffuse crackles were audible in both lungs. X-ray revealed diffuse bilateral airspace consolidation. Arterial blood gases on air showed PaO2 41 mm Hg, PaCO2 35 mm Hg, and pH 7.46. There was a restrictive pattern on pulmonary function testing. Fiberoptic bronchoscopy with broncho-alveolar lavage and transbronchial biopsy established the diagnosis of pulmonary alveolar proteinosis. Whole lung lavage lead to gradual improvement over the next few weeks. However, chest X-ray, arterial blood gases and pulmonary function tests failed to revert completely to normal. Such severe manifestations and such an aggressive course as in this case might have been prevented had the diagnosis been made and treatment instituted earlier in the course of the disease.

Adult↗
PubMed1994

Glutamine metabolism and utilization: relevance to major problems in health care.

Glutamine plays an important role in normal and pathophysiological states. In this review we describe the biochemical synthesis and degradation pathways of glutamine, as well as its utilization by the immune system and in rapidly dividing cells. Also discussed are glutamine behaviour in catabolic states and the therapeutic implications of this amino acid in total parenteral nutrition, digestive diseases and cancer.

Animals↗
PubMed1993

Comparison of the Gompertz and Weibull functions as descriptors for human mortality distributions and their intersections.

The Gompertz and Weibull functions are compared with respect to goodness-of-fit to human mortality distributions; ability to describe mortality curve intersections; and, parameter interpretation. The Gompertz function is shown to be a better descriptor for 'all-causes' of deaths and combined disease categories while the Weibull function is shown to be a better descriptor of purer, single causes-of-death. A modified form of the Weibull function maps directly to the inherent degrees of freedom of human mortality distributions while the Gompertz function does not. Intersections in the old-age tails of mortality are explored in the context of both functions and, in particular, the relationship between distribution intersections, and the Gompertz ln[R0] versus alpha regression is examined. Evidence is also presented that mortality intersections are fundamental to the survivorship form and not the rate (hazard) form. Finally, comparisons are made to the parameter estimates in recent longitudinal Gompertzian analyses and the probable errors in those analyses are discussed.

Adolescent↗
PubMed1993

The immunochemistry of sandwich ELISAs--VI. Greater than 90% of monoclonal and 75% of polyclonal anti-fluorescyl capture antibodies (CAbs) are denatured by passive adsorption.

Quantitative data are presented showing that the method most commonly used to immobilize antibodies in microtiter immunoassays functionally inactivates most of the antibodies. These results were collected using five affinity purified polyclonal antibodies (pAbs) and six monoclonal antibodies (mAbs) specific for fluorescein (FLU) as capture antibodies (CAbs). These CAbs were tested for their ability to capture FLU4.2-BSA after immobilization by passive adsorption, the Protein-Avidin-Biotin-Capture (PABC) system or using previously adsorbed anti-globulins. Results indicate that under optimal conditions, < 10% of monoclonal capture antibody equivalents (CAbeqv) and congruent to 22% of polyclonal CAbeqv remain functional after passive adsorption. Immobilization via the PABC system improved the performance of mAbs by more than five-fold but had less than a two-fold effect on pAbs. Many CAbs immobilized using an anti-globulin retained full activity including the ability to bind two molecules of FLU4.2-BSA/molecule of CAb. The latter result is not necessarily a recommendation for the use of anti-globulin immobilization, since the number of functional CAbeqv per well is not significantly greater than that which can be achieved using passive adsorption.

Adsorption↗
PubMed1993

Scanning electron microscopy of the Rhodnius neglectus (Hemiptera) labial salivary glands after starvation.

Labial salivary glands are found in the majority of insects. They are relatively large, extend back into the thorax, and in Rhodnius, they are cherry red in color due to a pigment derived from traces of hemoglobin absorbed form the gut. In most insects they are acinous shaped, with long excretion channels that present differentiated regions which from salivary reservoirs. The glands may be relatively simple or complexly branched and convoluted. In Rhodnius they are described as being unilobed with no traces of division. The main duct leaves the gland at its anterior extremity. The acini have different kinds of cells but all of them are seen as sources of secretion. Our material has a different shape due to the fact that the animals spent 20 days under starvation conditions. New data are also obtained through treatment with collagenase and HCl. The importance of the study of these glands lies in the fact that it will further understanding of the transmission of Chagas' disease.

Animals↗
PubMed1993

Correlation of human longevity oscillations with sunspot cycles.

An examination of past human mortality trends revealed that the mean longevity of birth cohorts from 1740 to 1900 for United States of America (U.S.) Congressional Representatives exhibited oscillations that coincided with the 9- to 12-year sunspot cycle. Cohort mean longevities were 2-3 years greater during times of low sunspot activity than at peak activity. This phenomenon was confirmed in data from members of the House of Commons of the United Kingdom Parliament and from University of Cambridge alumni. An additional longevity oscillation with a longer period was visible in the data and may also be related to sunspot cycles. The amplitude and frequency modulations in the longevity and sunspot oscillations aligned when a 20-year phase shift was incorporated. This shift requires the existence of a lag between solar changes and the affected birth cohorts. Several possible causes of the effect are discussed, in particular: radiation on primordial germ cells in developing embryos; influenza epidemics and pandemics; and weather. The size of the longevity oscillation requires that the solar effect must be considered in studies that examine longevity trends and risk estimation.

History, 18th Century↗
PubMed1992

The physical and functional behavior of capture antibodies adsorbed on polystyrene.

Six monoclonal and two polyclonal antibodies to fluorescein (FLU) were affinity purified and immobilized on Immulon 2 polystyrene as capture antibodies (CAbs): (a) by passive adsorption at pH 9.6, (b) via a streptavidin bridge to a biotinylated carrier molecule, and (c) via an antiglobulin which had been previously adsorbed passively to the polystyrene. Data show that less than 3.0% of the binding sites of monoclonal CAbs and approximately 5-10% of those of polyclonal CAbs were capable of capturing antigen (FLU4.2-BSA) after passive adsorption. Immobilization of CAbs via an antiglobulin or a streptavidin bridge, resulted in the preservation of antibody binding sites to greater than 70% for some monoclonals although immobilization via the streptavidin bridge resulted in the highest number of functional sites/well. The data presented are consistent with studies on other adsorbed proteins which demonstrate that passive adsorption on polystyrene results in the loss of protein function. Furthermore, these data show that generally less than half of the binding sites of antibodies available in solution are available after solid-phase immobilization even when non-adsorptive methods are employed. Some polyclonal anti-FLU also have lower average avidity following passive adsorption compared with CAbs immobilization via a streptavidin bridge. Immunochemical studies revealed that adsorbed polyclonal-CAbs performed like monoclonals when tested with multivalent antigens (FLU10-IgA) but in an expected heterogeneous manner in Scatchard plots when tested using univalent FLU-insulin. This observation implied cross-linking of immobilized CAbs by the multivalent antigen. Because only 5-10% of adsorbed polyclonal CAbs are active, the survivors must be non-randomly distributed in clusters to explain the cross-linking. This was confirmed by scanning electron microscopy which gave rise to the hypothesis that antibodies which retain activity after adsorption, are those present in clusters, i.e., the functional adsorbed CAb is an antibody cluster. Data presented in this report on the behavior of adsorbed CAbs, and reviewed from the work of others for various adsorbed proteins, indicate that the method of passive adsorption at pH 9.6, which is widely used in popular microtiter ELISAs, and which has in many ways revolutionized immunoassay, is a method of protein denaturation. Assayists that utilize passive adsorption of proteins on hydrophobic supports as part of their research need to be cognizant of this phenomenon, while inventors of immunoassay should develop alternative methods of immobilization which do not destroy 90% of the functional activity of solid-phase reactant.

Adsorption↗
PubMed1992

Human disease mortality kinetics are explored through a chain model embodying principles of extreme value theory and competing risks.

The distributions for human disease-specific mortality exhibit two striking characteristics: survivorship curves that intersect near the longevity limit; and, the clustering of best-fitting Weibull shape parameter values into groups centered on integers. Correspondingly, we have hypothesized that the distribution intersections result from either competitive processes or population partitioning and the integral clustering in the shape parameter results from the occurrence of a small number of rare, rate-limiting events in disease progression. In this report we initiate a theoretical examination of these questions by exploring serial chain model dynamics and parameteric competing risks theory. The links in our chain models are composed of more than one bond, where the number of bonds in a link are denoted the link size and are the number of events necessary to break the link and, hence, the chain. We explored chains with all links of the same size or with segments of the chain composed of different size links (competition). Simulations showed that chain breakage dynamics depended on the weakest-link principle and followed kinetics of extreme-values which were very similar to human mortality kinetics. In particular, failure distributions for simple chains were Weibull-type extreme-value distributions with shape parameter values that were identifiable with the integral link size in the limit of infinite chain length. Furthermore, for chains composed of several segments of differing link size, the survival distributions for the various segments converged at a point in the S(t) tails indistinguishable from human data. This was also predicted by parameteric competing risks theory using Weibull underlying distributions. In both the competitive chain simulations and the parametric competing risks theory, however, the shape values for the intersecting distributions deviated from the integer values typical of human data. We conclude that rare events can be the source of integral shapes in human mortality, that convergence is a salient feature of multiple endpoints, but that pure competition may not be the best explanation for the exact type of convergence observable in human mortality. Finally, while the chain models were not motivated by any specific biological structures, interesting biological correlates to them may be useful in gerontological research.

Computer Simulation↗
PubMed1992

Quantitative evidence that the genetic basis of human mortality operates at the translation level: a preliminary assessment.

The dying off of human population cohorts due to different age related diseases rigorously follows stochastically derived rules. The existence of such rules suggests a common, fundamental mechanism for human mortality. We show here, by a simple quantitative analysis, that the progressive loss with age of genetic triplet code information (anticodons) in body cells, as described by the statistics of extremes in order theory, serves as such a mechanism.

Adult↗
PubMed1992

Low to moderate intensity endurance training in healthy older adults: physiological responses after four months.

OBJECTIVE: To determine the physiological adaptations in previously sedentary healthy older men and women (mean age = 68) to a 16-week low-to-moderate-intensity exercise program. DESIGN: Randomized, controlled trial. SETTING: An exercise facility and testing laboratory in a gerontological research institute. PARTICIPANTS: Two-hundred forty-seven community-dwelling older persons free of significant cardiovascular, pulmonary, or uncontrolled metabolic disease, anemia, electrolyte abnormality, resting BP of 165/90 or greater, or chronic disease affecting the ability to exercise on a bicycle. INTERVENTION: Subjects were randomly assigned to either an exercise (n = 166) or attention control group (n = 81). Exercisers trained thrice weekly for 40 minutes on a cycle ergometer (5-minute warm up, 30 minutes at training heart rate (THR), 5-minute cool down). THR was set at 70% of peak heart rate attained on a maximal exercise test (mean = 115 +/- 15). Control subjects attended weekly group talks. Testing took place before and after the program. RESULTS: Peak attained oxygen uptake (VO2max) increased 8.5% in exercisers and decreased slightly in controls (p less than .001) and oxygen uptake at ventilatory threshold (VeT VO2) increased by 3.5% in exercisers and decreased by 3% in controls (p less than .001). This pattern of a greater increase in VO2max than VeT VO2 is different from that seen in young and middle-aged subjects. CONCLUSION: This study demonstrated that a large scale training program is feasible for healthy older people, that physiologic improvements can be measured after 16 weeks of low-to-moderate-intensity training, and that mechanisms of adaptation to exercise may be different in elderly subjects from those in younger ones.

Adaptation, Physiological↗
PubMed1991

An unexpected periodicity among the prevalences of human age-related, mortal diseases.

A periodic pattern was discovered among the relative number of deaths per year for the major age-related diseases in humans. This pattern was observed among 178 causes-of-death composed of male and female. White (U.S.A.), Black (U.S.A.) and Japanese (Japan) populations. Both descriptive (Fourier transform) and statistical analysis procedures revealed evidence that the pattern resulted from the presence of an underlying power progression between disease prevalences, with a factor of approximately 2.0 between sizes. This periodicity was highly unlikely to have occurred by chance (P much less than 0.01). The presence of such a power progression suggests that the sizes of the various fractions of the total population, that are afflicted with these mortal diseases, are determined by forces intrinsic to the population and probably result from a common mechanism.

Age Factors↗