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Biomedical subjects

R J Levine

Publications and source records attributed to R J Levine.

At least 19 recordsLinked to original sources

Air-conditioned environments do not prevent deterioration of human semen quality during the summer.

OBJECTIVE: To determine if air conditioning might mitigate summer reductions in semen quality. DESIGN: Prospective study of semen quality in summer and winter. SETTING: Normal human volunteers were studied in the setting of a fertility laboratory. PATIENTS, PARTICIPANTS: Two groups of volunteers were selected from the vicinity of New Orleans: 64 men who worked indoors during the summer in air-conditioned environments and 76 others who worked outdoors. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Parameters of manual semen analysis were examined for seasonal and group differences. RESULTS: Remarkably similar reductions in semen quality during summer as compared with winter were observed in both indoor and outdoor workers, respectively, with regard to the following parameters of semen quality: 19% and 19% in sperm concentration, 25% and 27% in total sperm per ejaculate, 17% and 20% in motile sperm concentration, 13% and 15% in percent sperm with normal morphology, and 23% and 23% in concentration of morphologically normal motile sperm. CONCLUSIONS: These findings do not support the hypothesis that the heat of the summer is detrimental to male reproductive capacity. The available evidence suggests instead a possible role of photoperiod in causing the seasonal changes in semen quality.

Adolescent

Situation ethics.

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Clinical Competence

Mortality of iron foundry workers. II. Analysis by work area.

Plantwide analyses of the mortality experience of 8147 foundrymen revealed excesses for several diseases including lung cancer. Using indirect measures of smoking, it appeared that most, if not all, of the excess of lung cancer deaths could be explained by smoking habits. To explore further the possible association between these mortality excesses and foundry exposures, jobs were grouped into six work areas on the basis of similarities in production processes. The findings of analyses by work areas support the inferences from plantwide observations. No evidence was found of a relationship between lung cancer and foundry exposures. The pattern of mortality from emphysema and cerebrovascular disease in the different work areas paralleled that of lung cancer, suggesting that mortality from these diseases may have been influenced by a common etiologic agent, probably tobacco smoke. The data also reveal possible associations between metal pattern-making and colon cancer, silica or metal dust and stomach cancer, and carbon monoxide and ischemic heart disease.

Adult

Deferred consent.

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Clinical Trials as Topic

Effects of phosphorylation by myosin light chain kinase on the structure of Limulus thick filaments.

The results discussed in the preceding paper (Levine, R. J. C., J. L. Woodhead, and H. A. King. 1991. J. Cell Biol. 113:563-572.) indicate that A-band shortening in Limulus muscle is a thick filament response to activation that occurs largely by fragmentation of filament ends. To assess the effect of biochemical changes directly associated with activation on the length and structure of thick filaments from Limulus telson muscle, a dually regulated tissue (Lehman, W., J. Kendrick-Jones, and A. G. Szent Gyorgyi. 1973. Cold Spring Harbor Symp. Quant. Biol. 37:319-330.) we have examined the thick filament response to phosphorylation of myosin regulatory light chains. In agreement with the previous work of J. Sellers (1981. J. Biol. Chem. 256:9274-9278), Limulus myosin, incubated with partially purified chicken gizzard myosin light chain kinase (MLCK) and [gamma 32P]-ATP, binds 2 mol phosphate/mole protein. On autoradiographs of SDS-PAGE, the label is restricted to the two regulatory light chains, LC1 and LC2. Incubation of long (greater than or equal to 4.0 microns) thick filaments, separated from Limulus telson muscle under relaxing conditions, with either intact MLCK in the presence of Ca2+ and calmodulin, or Ca2(+)-independent MLCK obtained by brief chymotryptic digestion (Walsh, M. P., R. Dabrowska, S. Hinkins, and D. J. Hartshorne. 1982. Biochemistry. 21:1919-1925), causes significant changes in their structure. These include: disordering of the helical surface arrangement of myosin heads as they move away from the filament backbone; the presence of distal bends and breaks, with loss of some surface myosin molecules, in each polar filament half; and the production of shorter filaments and end-fragments. The latter structures are similar to those produced by Ca2(+)-activation of skinned fibers (Levine, R. J. C., J. L. Woodhead, and H. A. King. J. Cell Biol. 113:563-572). Rinsing experimental filament preparations with relaxing solution before staining restores some degree of order of the helical surface array, but not filament length. We propose that outward movement of myosin heads and thick filament shortening in Limulus muscle are responses to activation that are dependent on phosphorylation of regulatory myosin light chains. Filament shortening may be due, in large part, to breakage at the filament ends.

Actin Cytoskeleton

The effect of calcium activation of skinned fiber bundles on the structure of Limulus thick filaments.

Here we present evidence that strongly suggests that the well-documented phenomenon of A-band shortening in Limulus telson muscle is activation dependent and reflects fragmentation of thick filaments at their ends. Calcium activation of detergent-skinned fiber bundles of Limulus telson muscle results in large decreases in A-band (from 5.1 to 3.3 microns) and thick filament (from 4.1 to 3.3 microns) lengths and the release of filament end fragments. In activated fibers, maintained stretched beyond overlap of thick and thin filaments, these end fragments are translocated to varying depths within the I-bands. Here they are closely associated with fine filamentous structures that also span the gap between A- and I-bands and attach to the distal one-third of the thick filaments. End-fragments are rarely, if ever, present in similarly stretched and skinned, but unstimulated fibers, although fine "gap filaments" persist. Negatively stained thick filaments, separated from skinned, calcium-activated, fiber bundles, allowed to shorten freely, are significantly shorter than those obtained from unstimulated fibers, but are identical to the latter with respect to both the surface helical array of myosin heads and diameters. Many end-fragments are present on grids containing thick filaments from activated fibers; few, if any, on those from unstimulated fibers. SDS-PAGE shows no evidence of proteolysis due to activation and demonstrates the presence of polypeptides with very high molecular weights in the preparations. We suggest that thick filament shortening is a direct result of activation in Limulus telson muscle and that it occurs largely by breakage within a defined distal region of each polar half of the filament. It is possible that at least some of the fine "gap filaments" are composed of a titin-like protein. They may move the activation-produced, fragmented ends of thick filaments to which they attach, into the I-bands by elastic recoil, in highly stretched fibers.

Actin Cytoskeleton

Medicalization of psychoactive substance use and the doctor-patient relationship.

Any attempt at medicalization of cocaine, heroin, marijuana, and other psychoactive substances of abuse in the United States is likely to encounter strong opposition by many responsible physicians. Such opposition would be grounded in their perception that medicalization would be contrary to the purposes of medical practice. Most physicians would, however, be willing to consider prescribing such substances for pathological users if such prescribing took place within the context of a fully developed doctor-patient relationship in which the patient recognized the dependency as undesirable and wanted to cooperate with the physician in a mutual effort to end the dependency or, if this were not feasible, to mitigate its destructive effects.

Behavior Control

Differences in the quality of semen in outdoor workers during summer and winter.

BACKGROUND AND METHODS: In warm climates throughout the world, there is a deficit of births during the spring season. To determine whether this deficit might reflect a deleterious effect of heat on the male reproductive capacity during the previous summer, we obtained semen specimens in summer and winter from normal men who worked outdoors in the vicinity of San Antonio, Texas, and we performed automated semen analyses with an image-analysis system. RESULTS: Pairwise comparisons among 131 men without azoospermia who contributed specimens in both summer and winter revealed significant reductions during the summer in sperm concentration, total sperm count per ejaculate, and concentration of motile sperm. The mean decreases in these values after adjustment for potential confounding characteristics were 32 percent (95 percent confidence limits, 28 and 44 percent), 24 percent (95 percent confidence limits, 18 and 43 percent), and 28 percent (95 percent confidence limits, 24 and 44 percent), respectively (P less than 0.0001). The lower a subject's average sperm concentration and motile-sperm concentration, the greater the reduction. We found no correlation, however, between the number of hours per day spent working during summer in settings without air conditioning and either the summer sperm concentration or the difference in concentration between summer and winter. Among the children of the men in the study whose wives were living near San Antonio during the year before they gave birth, a disproportionately low number were born during the spring. CONCLUSIONS: Semen quality deteriorates during the summer. This phenomenon may account at least in part for the reduction in the birth rate during the spring in regions with warm climates.

Adult

Ethics in cardiovascular medicine. Task Force IV: Scientific responsibility and integrity in medical research.

Ethical standards are a set of affirmative responsibilities to which the investigator must subscribe; behavior that is incompatible with these responsibilities should be presumed unethical, whether or not it is explicitly proscribed. This Task Force sought to present these standards as principles or guidelines. In undertaking research an investigator must accept that publicly funded or supported research is intended to yield public benefit; personal gain should be only incidental to and not at the expense of the public benefit. The responsibilities of the investigator are summarized as follows: Design of Research To develop a research design that effectively and efficiently addresses the scientific question while minimizing the likelihood of incorrect or misleading results. To protect the rights and welfare of human subjects, assure the humane use of laboratory animals and protect the safety of laboratory workers and the environment. Conduct of Research To ensure that accepted laboratory and research practices are followed and that all data are accurately collected and properly recorded; the investigator must participate in the review of original data. To carry out research in accordance with that approved by the institutional review board and ensure that fully informed consent is obtained, that the welfare of human subjects is protected and that animal welfare and laboratory safety procedures are carried out. To provide effective ongoing supervision of research trainees and technicians. In multidisciplinary collaborative research, to have at least an overview familiarity with the work outside his or her areas of expertise. In fixed protocol, multicenter collaborative research the investigator must be satisfied with the adequacy of the collaborative activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomedical Research

Assigning race to occupational cohorts using census block statistics.

Race is an important determinant of disease frequency, yet the race of subjects in retrospective epidemiologic studies is frequently unknown. If addresses are available, the race of study subjects may be estimated from the racial composition of the blocks on which they have resided. Such information can be obtained from census block statistics for Standard Metropolitan Statistical Areas and, with the 1990 Census, probably for the entire United States. The authors assigned black race to persons on blocks with greater than 60% black residents and white race to those residing on blocks containing less than 40% blacks. The validity of the procedure was tested on 341 decedents of known race who resided at the time of death within the Detroit, Michigan, Standard Metropolitan Statistical Area. Thirteen individuals who lived on blocks with 40-60% blacks were excluded from analysis, as well as 18 others for whom racial composition of blocks could not be ascertained. In 293 (94%) of the remaining 310 persons, race assigned on the basis of census information agreed with race obtained from death certificates. This method should prove useful for assigning race to study subjects lacking racial identification.

Black or African American

Mortality of iron foundry workers: I. Overall findings.

A retrospective cohort mortality study was conducted among 8147 men and 627 women employed in a gray iron foundry for at least 6 months between 1950 and 1979. More than 1700 deaths occurred during a 35-year period of observation. Standardized mortality ratios (SMRs) for all causes were close to expected values based on the US general population as the standard. The mortality of nonwhite men was significantly increased for lung cancer (SMR 132) and ischemic heart disease (SMR 126). Other moderate, but nonsignificant excesses were noted among nonwhite men for cancers of the stomach, pancreas, and prostate, for diabetes mellitus and pulmonary emphysema, and among white men for cancers of the lung and stomach, gastric and duodenal ulcers, pulmonary emphysema, and suicide. Small mortality increases were observed in both racial groups for cerebrovascular disease. The lack of a trend with time since hire and duration of foundry employment suggests that lung cancer mortality may not be associated with exposure to the foundry environment. Utilizing indirect measures of smoking, it appears that virtually all excess lung cancer deaths among whites and at least some of the excess among nonwhites could be explained by smoking habits. Similarly, smoking may have been responsible for the mortality excesses from emphysema, cerebrovascular diseases, and ischemic heart disease.

Adult

Fertility among Danish male welders.

Welding may be detrimental to the male reproductive system. Fertility was examined in a Danish cohort of 3702 male metalworkers over a follow-up of 47 674 person-years. Occupational histories were gathered by postal questionnaires. Information on births was obtained by record linkage to the Danish Central Population Register. Among persons who had ever worked as welders, the probability of having a child was slightly reduced the year after a year of welding exposure, even after control for differences in age, birth cohort, paternal parity, birth of a child in the preceding five years, smoking, and consumption of alcoholic beverages (odds ratio 0.89, 95% confidence interval 0.83-0.97). The reduction in fertility was associated with the welding of mild steel, but not with the welding of stainless steel. These findings are consistent with results of previous studies of time to conception and semen quality in welders.

Adult

Fibre types in Limulus telson muscles: morphology and histochemistry.

Using a variety of techniques, we have demonstrated the presence of at least two fibre types in Limulus median telson levator muscle. By light and electron microscopy, large (2,156 microns 2 mean cross-sectional area) fibres have A-bands of 4.1 microns, one-half I bands of 2.15 microns and Z lines less than or equal to 0.5 microns in width. Few mitochondria are found in these fibres, which comprise 54% of those present in a given microscope field and which occupy 82% of the total cross-sectional area. Small fibres (484 microns 2 mean cross-sectional area) have A bands of 6.3 microns, one-half I bands of 3.1 microns and Z lines between 0.5 and 1.0 microns in width and are rich in mitochondria. Although small fibres comprise nearly one-half (46%) of the fibres in a field, they occupy only 18% of the total cross-sectional area. Histochemical staining for alkaline-stable myofibrillar ATPase activity and mitochondrial reduced beta-nicotinamide adenine nucleotide (beta-NADH) tetrazolium reductase activity confirms the presence of two fibre types. The large fibres react positively for the myofibrillar ATPase activity and negatively for the mitochondrial enzyme activity. The reverse is seen with the small fibres. Some fibres of intermediate size, having intermediate staining characteristics, were also observed. Native gel electrophoresis of both myofibrillar and purified myosin preparations supports the observed differences in myofibrillar ATPase activity in that two myosin isozymes are resolved on pyrophosphate gels. Although the thick filaments isolated from unstimulated small fibres are longer (greater than 6.0 microns) than those isolated from unstimulated large fibres (4.26 microns), all have a similar appearance with respect to the arrangement of myosin heads on their surfaces, and similar diameters. The implications of the observed heterogeneity of fibre types is discussed with reference to previously reported phenomena in Limulus telson muscle, including changes in length of thick filaments on fibre stimulation and the shape of the length-tension curve obtained from fibre bundles.

Animals

Computer-assisted semen analysis: results vary across technicians who prepare videotapes.

Automated semen analyses revealed differences of 21% to 30% in concentration-related parameters and 5% to 11% in motion-related parameters between means of groups of replicate specimens. Disparities among videotapes produced by two laboratory technicians accounted for the divergence in concentration-related parameters. This resulted partially from differences between the two technicians in propensity to dilute concentrated specimens. The causes of the greater portion of disparities between videotaping technicians, however, have not been identified. Differences in motion-related parameters could not be ascribed to technicians, but the basis for these differences is also unknown. The results suggest that values obtained from the CellSoft image analysis system may not be comparable between technicians or laboratories, despite use of identical computer parameter settings. Until effective quality control measures have been implemented, such comparisons must be made with caution.

Diagnosis, Computer-Assisted

Urinary creatinine excretion is not stable: a new method for assessing urinary toxic substance concentrations.

Urinary concentrations of toxic substances require correction to adjust for the misleading effects of varying states of hydration. The most common method in current use involves calculation of substance-to-creatinine concentration ratios. For accuracy, this method assumes creatinine excretion rates to be stable despite varying rates of urinary flow. However, this underlying assumption has been challenged in recent studies. Our evaluation of separate data regarding individual voids confirmed that creatinine excretion rate depends significantly (p less than .0001) on urinary flow. We calculated a logarithmic regression model identical to one reported previously. The partial correlation coefficient for log flow was .21 after adjusting for inter-individual differences in creatinine excretion rates. We propose a simple method to correct creatinine concentrations in "spot" urine samples for the effects of varying hydration. The new method retains many benefits of the classical correction by substance-creatinine ratios.

Creatinine