Thermoregulatory and cardiorespiratory responses to bicycling 55 km (mean speed 9.7 m X s-1) outdoors (15 degrees C DB) were compared to equivalent cycle ergometry (90 min at 65% VO2max) in the laboratory (20-23 degrees C DB, 50% RH) in 7 trained cyclists. Outdoor environmental conditions were simulated with fans and lamps, and were contrasted with standard no-wind, no-sun laboratory conditions. Sweating rate was similar during outdoor and laboratory simulated outdoor cycling (0.90 and 0.87 to 0.94 1 X h-1 respectively). During outdoor bicycling, mean heart rate (161 bt X min-1) was 7-13% higher (p less than .05) than under laboratory conditions, suggesting a greater strain for a similar external work rate. The increase in rectal temperature (0.8 degrees C) was 33-50% less (p less than 0.05) at the cooler outdoor ambient temperature than in the laboratory. Thermoregulatory stress was greater under the no-fan, no-lamp laboratory condition than during simulated outdoor conditions (36-38% greater (p less than 0.05) sweating rate, 15-18% greater (p less than 0.01) mean skin temperature, 6.4 to 7.8 fold greater (p less than 0.01) amount of clothing-retrained sweat). The cooling wind encountered in actual road bicycling apparently reduces thermoregulatory and circulatory demands compared with stationary cycle ergometry indoors. Failure to account for this enhanced cooling may result in overestimation of the physiological stress of actual road cycling.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

A new serum proteolytic enzyme in aneurysm pathogenesis.

Despite significant progress in elucidating the pathogenesis of aneurysmal disease, the precise etiology of arterial wall degradation remains unclear. Numerous etiologies have been implicated, including stress-strain factors, structural wall abnormalities, and enzyme imbalance. We have previously shown that collagenase and elastase are increased in aortic aneurysm tissue. Herein we report and characterize a newly described serum compound that is able to hydrolyze an artificial elastase substrate but is not elastase. This substance is elevated in patients with atherosclerotic disease and, following aneurysmectomy, its concentration increases by threefold. Examination of the substance reveals that it is bound to lipid and consists of four subunits of molecular weights: 310,000, 62,000, 40,000, and 10,000 daltons. It has characteristics of thiol, carboxyl, and metalloenzymes and is most active at a pH of 7.0 to 8.0. A relationship between this serum compound and aneurysm tissue enzymatic activity is noted. We postulate that this serum compound may be produced by mononuclear cells and released into the serum. Furthermore, monocytes may enter the arterial wall intima and release this substance, resulting in proteolytic arterial wall degradation and subsequent aneurysm formation.

Aortic Aneurysm↗

PubMed1985

Use of monoclonal antibodies in an epidemiological marker system: a retrospective study of lung specimens from the 1976 outbreak of Legionnaires disease in Philadelphia by indirect fluorescent-antibody and enzyme-linked immunosorbent assay methods.

Autopsy specimens of lung tissues from 15 patients that contracted legionellosis during the 1976 Philadelphia outbreak of Legionnaires disease were examined for the presence of Legionella organisms and soluble antigens by indirect fluorescent-antibody (IFA) testing and by an enzyme-linked immunosorbent assay (ELISA) with both polyclonal and monoclonal antibodies. In all 15 cases, at least one specimen was positive for Legionella pneumophila serogroup 1 (Lp-1) antigens by a polyclonal antibody ELISA system. Of the 15 cases tested for Lp-1, 9 were positive by a polyclonal antibody IFA test. Nine mouse monoclonal antibodies to Lp-1 gave essentially the same reactivity pattern with extracts from lung tissue homogenates as that obtained with a Philadelphia 1 culture extract by using a monoclonal antibody ELISA system. The same monoclonal antibody panel gave similar results when used in the IFA system with tissue homogenates. Monoclonal antibodies can be used as epidemiological marker systems with both IFA and ELISA testing. This study provides evidence that the 1976 common source outbreak in Philadelphia was probably caused by a single Lp-1 strain. ELISA testing of the soluble antigen of Lp-1 from lung tissue homogenate supernatants was more sensitive than IFA testing of the homogenates and should be extremely useful as either a primary test or as an adjunct to fluorescent antibody testing for legionellosis.

Antibodies, Bacterial↗

PubMed1985

Quantitative risk assessment of environmental hazards.

Quantitative risk assessment may never become a rigorous scientific discipline because of the inherent difficulties in working with highly uncertain and often controversial data and methods, and because the predictions of risk assessment may not be subject to validation in their most important areas of application. However, the potential benefits of having quantitative estimates of risk may make quantitative risk assessment a valuable adjunct to traditional methods for making individual and social decisions about health hazards in the home, workplace, and general environment. Risk assessment, which is the process of estimating risks to populations exposed to hazardous agents or activities, must be distinguished from risk management, which is the process of forming and implementing a strategy for accepting or abating the risks. To the extent possible, these two processes should be kept separate. Quantitative risk assessment is in principle capable of estimating individual or lifetime excesses of specific health effects from exposures to a specified hazard. These excesses may be estimated on an absolute basis or expressed as a relative risk in comparison with the baseline risk that would exist without exposure. An individual risk is usually expressed in terms of the probability of developing the health effect in some time period following a specified exposure, whereas a population risk is the overall number of effects expected in a defined population with a defined distribution of exposure levels and patterns. The variation of risk with time after exposure may imply a constant absolute risk, a constant relative risk, or some other dependence on time, usually after a minimal latent period has elapsed. Risk estimates can rarely be made directly from observed human data, and models for extrapolating or projecting risk estimates from the conditions of observation to the actual conditions of exposure must be used. Dose-response relationships are used for extrapolating from high laboratory or occupational exposures to low exposures encountered more frequently in human populations. Thresholds of dose or nonlinear dose-response relationships may be related to nonlinear pharmacokinetics prior to the ultimate exposure of the critical organ to the proximate carcinogen or other hazardous agent. Time-response models estimate risks for periods after exposure longer than have been observed in epidemiologic studies. Extrapolations from experiments with laboratory animals to humans are made difficult because of great differences in size, lifespan, physiology, and metabolism between human and animal.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1985

Suppression of T lymphocyte chemotactic factor production by the opioid peptides beta-endorphin and met-enkephalin.

The opioid peptides beta-endorphin and met-enkephalin have been shown to modulate human lymphocyte proliferation, mononuclear cell locomotion, natural killer cell activity, and neutrophil locomotion. This study demonstrates that beta-endorphin and met-enkephalin inhibit the production of a T lymphocyte chemotactic factor (LCF) by concanavalin A (Con A)-stimulated peripheral blood mononuclear cells. Inhibition of LCF production was observed by using concentrations of 10(-11) to 10(-6) M beta-endorphin or met-enkephalin but not alpha-endorphin. A bimodal pattern of suppression of LCF production was observed with both met-enkephalin and beta-endorphin when titrated from 10(-12) to 10(-6) M concentrations, with the peaks of suppressive activity occurring at concentrations of 10(-11) M and 10(-6) M. Timed studies of the production of LCF over a 54-hr period showed that there was an appreciable lag in the onset of measurable LCF activity in mononuclear supernatants produced in the presence of beta-endorphin and met-enkephalin. The suppression of LCF production mediated by opioid peptides in mononuclear supernatants was abrogated by depletion of glass-adherent mononuclear cells before culturing with opioids and Con A. The inhibitory effect of opioid peptides on LCF production was prevented by the addition of indomethacin to cell cultures. Additional experiments showed that exogenous prostaglandin E2 (PGE2) suppressed Con A-stimulated LCF production when added at concentrations ranging from 10(-6) to 10(-8) M. Other studies suggested that the mechanism of opioid peptide-mediated suppression of LCF production was due to an enhanced sensitivity of mononuclear cells to the inhibitory action of PGE2. These data provide further evidence for modulation of the immune response in humans by the neuroendocrine hormones beta-endorphin and met-enkephalin and further suggest a link between this modulation and arachidonic acid metabolism.

Cell Separation↗

PubMed1985

Differential Ia antigen expression by autologous human erythroid and B lymphoblastoid cell lines.

Human erythroid precursors express Ia antigens that have serology, function, molecular nature, and genetic regulation that are largely unknown. To approach these issues, Ia+ and Ia- subclones of the HEL human erythroleukemia cell line (HEL-DR+ and HEL-DR-, respectively) and an autologous B lymphoblastoid line (B line) were isolated. These erythroid and lymphoid lines were compared with respect to their binding of monoclonal HLA-D subregion-specific antibodies, the ability to trigger in vitro alloproliferation, expression of class II molecules, and transcription of class II-related genes. Unlike the DP+/DQ+/DR+ B lines, HEL-DR+ differentially expressed DP and DR, but not DQ specificities. Also unlike the autologous B line, HEL-DR+ appeared to be unable to trigger primary or secondary allogeneic T cell proliferation, despite the presence of responder monocytes in these cultures and irrespective of lymphokine addition. HEL-DR+ expression of bona fide class II molecules similar to B line DR heterodimers was verified by two-dimensional gel electrophoresis of material immunoprecipitated from 125I-labeled cells. Northern blot analysis of cytoplasmic RNA from these lines indicated that differential class II gene transcription could readily explain the distinct, lineage-related Ia phenotypes of HEL-DR+ and B line. In addition, the lack of invariant chain and class II transcripts in HEL-DR- implied that expression of these unlinked genes in HEL cells is co-regulated.

Antigen-Antibody Reactions↗

PubMed1984

Bias against women persists in medicine.

Explore the source record for details and available documents.

Female↗

PubMed1984

Agonists differentiate muscarinic receptors that inhibit cyclic AMP formation from those that stimulate phosphoinositide metabolism.

Muscarinic receptor stimulation elicits two distinct biochemical responses in embryonic chick heart cells: inhibition of catecholamine-stimulated cyclic AMP formation and stimulation of phosphoinositide (PhI) hydrolysis. We observe two major differences in the effects of agonists on these responses. First, carbachol and oxotremorine both inhibit cyclic AMP formation, but only carbachol stimulates PhI hydrolysis. Second, the dose-response relationships for the cyclic AMP and PhI responses differ; the half-maximal concentrations of carbachol needed to inhibit cAMP accumulation and stimulate PhI hydrolysis are 2 X 10(-7) and 2 X 10(-5) M, respectively. We carried out radioligand binding studies on intact chick heart cells to determine whether these data could be explained in terms of different agonist binding states of the muscarinic receptor. In intact cells, carbachol competes for [3H]quinuclidinyl benzilate-binding sites with high and low affinity, while oxotremorine shows only high affinity binding. We suggest that the receptor state common to both agonists is the state associated with inhibition of adenylate cyclase, while the very low affinity binding site seen only with carbachol is associated with the PhI response. We also consider the possibility that both responses are caused by a single receptor state that is efficiently coupled to adenylate cyclase inhibition and inefficiently coupled to PhI hydrolysis. Whichever mechanism is correct, our findings demonstrate that muscarinic receptors coupled to adenylate cyclase and the PhI response can be differentiated by virtue of their sensitivity to agonist and the efficiency with which some agonists induce receptor change and elicit receptor-mediated biochemical responses.

Animals↗

PubMed1984

Survival of alcoholic v nonalcoholic patients after portasystemic shunts.

Controversy persists over the comparative survival of alcoholic v nonalcoholic cirrhotic patients who have had portasystemic shunts for therapeutic variceal decompression. We performed a matched retrospective study of 20 alcoholic cirrhotic patients and 20 nonalcoholic cirrhotic patients to determine any difference in survival between these groups and whether this correlated to the results of liver function tests. Patients were matched for age, urgency of operation, number of prior bleeding episodes, and Child's classification. Preoperative levels of albumin, bilirubin, alkaline phosphatase, and prothrombin time were similar in both groups. Operative mortality was 5% in the alcoholic cirrhotic group and 15% in the nonalcoholic group. Average long-term survival was 36 months in the alcoholic group and 43 months in the nonalcoholic group. Preoperative liver function parameters did not correlate with survival. Based on this data, we concluded that the results of preoperative liver tests did not correlate with survival in either group, long-term survival is similar in both groups after portasystemic shunts, and the difference in survival previously reported after a portasystemic shunt may pertain only to high-risk patients.

Adult↗

PubMed1984

Retrospective examination of lung tissue specimens for the presence of Legionella organisms: comparison of an indirect fluorescent-antibody system with direct fluorescent-antibody testing.

Although direct fluorescent-antibody (DFA) testing has been used successfully for a number of years to detect legionellae in clinical specimens, the number of known species and serogroups of Legionella has now increased to such an extent that the performance of DFA testing for all serological variants is impractical. Lung homogenates that were submitted to the Centers for Disease Control, Atlanta, Ga., from patients with suspected legionellosis, from November 1977 through May 1982, were originally screened by DFA testing. In our study 498 of these lung homogenates were screened by indirect fluorescent-antibody (IFA) testing, using a panvalent antiserum pool containing antibodies to 25 serological variants of Legionella spp. Fluorescein isothiocyanate-labeled goat anti-rabbit immunoglobulin was used as the second antibody of the sandwich system. For positive homogenates, i.e., those containing Legionella organisms, species and serogroup identification was made by IFA staining with polyvalent serum pools and then with monovalent antiserum. Of the 498 homogenates screened, 39 (7.8%) were positive by IFA testing. Four (0.8% of total; 10.3% of positive homogenates) of these had previously been negative by DFA testing, but subsequent testing showed that they contained Legionella organisms for which DFA reagents were not available at the initial screening. All specimens that were positive by DFA testing were also positive by IFA testing. IFA testing with polyvalent antisera is a simple, efficient method which is at least as sensitive as DFA testing and which can be used by clinical laboratories to cope with the increasing number of known serological variants of Legionella spp.

Antibodies, Bacterial↗

PubMed1984

Temperature-induced changes in neuromuscular function: central and peripheral mechanisms.

Three series of experimental tests were conducted on subjects under both elevated and depressed thermal conditions. Tripartite series consisted of whole-body immersion excepting the head, whole-body immersion excepting the head and response limb, and immersion of the discrete-response limb. Measures of physiological and behavioural responses were made at sequential .4 degrees C changes during whole-body immersions and approximately 5 degrees C changes of water temperature during the immersion of a limb only. Results suggested that velocity of nerve conduction decreased with thermal depression. Premotor, motor, simple, and choice reaction times varied differentially as a function of the hot and cold conditions. Implications of these differential effects on neuromuscular function are examined with respect to person-machine performance in artificially induced or naturally occurring extremes of ambient temperature.

Adult↗