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Biomedical subjects

R M Rose

Publications and source records attributed to R M Rose.

At least 37 records · Page 2Linked to original sources
PubMed1994

Human immunodeficiency virus type 1 infection of human macrophages modulates the cytokine response to Pneumocystis carinii.

The present studies examined production of the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 by human monocyte-derived macrophages exposed to Pneumocystis carinii in vitro and the impact of concurrent macrophage infection with human immunodeficiency virus type 1 (HIV-1) on these cytokine responses. Macrophages were infected with the HIV-1 BaL monocytotropic strain for 10 to 14 days and then exposed to P. carinii. At various times following P. carinii treatment, culture supernatants were harvested to assess the cytokine profile. Addition of P. carinii to HIV-uninfected macrophages resulted in augmented production of IL-6, TNF-alpha, and IL-1 beta protein. By contrast, in HIV-infected macrophages exposed to P. carinii, only the release of IL-6 was increased compared with that for HIV-uninfected macrophages, while the levels of TNF-alpha and IL-1 beta decreased. This altered response was confirmed at the molecular level for TNF-alpha mRNA. Preventing physical contact between P. carinii and macrophages by a membrane filter inhibited all cytokine release. Substituting P. carinii with a preparation of P. carinii 95- to 115-kDa major membrane glycoprotein A yielded a response similar to that obtained by addition of intact P. carinii. These results suggest that HIV-1 infection of human macrophages modulates cytokine responses to P. carinii.

AIDS-Related Opportunistic Infections↗
PubMed1994

Abnormal lipid composition of bronchoalveolar lavage fluid obtained from individuals with AIDS-related lung disease.

Surfactant lipids are not only important to the physiologic function of the lungs, but may also influence disease processes like Pneumocystis pneumonia, in which the interaction of host-defense cells with pathogen occurs within the confines of the surfactant-rich alveolar hypophase. In the present studies the lipid profile of bronchoalveolar lavage fluid (BALF) was characterized in subjects with AIDS-related lung diseases including Pneumocystis pneumonia. BALF lipid and total protein measurements were made in 43 subjects with acquired immune deficiency syndrome (AIDS)-related lung disease and compared with those made in 50 normal human immunodeficiency virus (HIV)-seronegative controls. The AIDS patient samples contained significantly greater amounts of total cholesterol, phosphatidylglycerol (PG), and protein than the control samples; in contrast to previous observations in rodent P. carinii infection, no differences were seen in total phospholipid (PL) or phosphatidylcholine (PC) in the two groups. The proportions of several of these lipids were deranged in BALF obtained from the patient group: PG/PL and PC/cholesterol differed significantly from normal samples. In the subset of patients with AIDS-related Pneumocystis pneumonia, no correlation was apparent between discrete BALF lipids and clinical indices reflective of disease severity. Using these measurements to approximate the lipid composition of the alveolar microenvironment in AIDS-related lung disease, we performed experiments in which normal human alveolar macrophages were exposed to exogenous liposomal lipids and then challenged with P. carinii. The ingestion but not binding of P. carinii by macrophages was diminished as a result of lipid exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1994

Long-term performance and wear of ultrahigh-molecular-weight polyethylene in total joint replacement prostheses: a brief overview and perspective.

Ultrahigh-molecular-weight polyethylene (UHMWPE) is used extensively in total joint replacements, particularly in hip and knee joints. At present, there is extensive concern with the long-term consequences of wear of this material, specifically osteolytic reactions to wear debris. The relationship of wear behavior to polymer morphology is almost completely unknown. Information on the effects of radiation sterilization on crystallinity is available, but gross conflicts exist. A central problem is the release, over long time periods, of huge numbers of submicron particles by wear. It has not been generally recognized that short-term, severe wear and long-term wear of UHMWPE in total joint replacements are very different in character and results. When the long-term wear regime is correctly defined, it is clear that knowledge of the influence of structure and properties on this specific phenomenon is almost completely absent.

Humans↗
PubMed1994

Predicting astronaut effectiveness: a multivariate approach.

In this study, measures of astronaut effectiveness were administered to volunteers from the astronaut corps in order to validate psychological "select-in" criteria for long-duration space missions. Using a peer nomination format, astronauts rated their peers with whom they had either flown or trained. Factor analysis revealed two latent performance dimensions: job competence and group living. The job competence dimension measured the instrumental aspects relating to job knowledge and job performance. The group living dimension measured the interpersonal aspects relating to teamwork and desirability as a colleague on Space Station. Analyses revealed that the personality variables could explain a significant proportion of the variance in the group living performance dimension, but not the job competence performance dimension. The findings are not surprising since astronauts are highly screened on the basis of past attainment, but are not as highly screened on aspects relating to teamwork and interpersonal concerns.

Astronauts↗
PubMed1994

Psychological predictors of astronaut effectiveness.

Are the personality characteristics of astronauts related to their professional effectiveness? In order to answer this question, effectiveness and personality data were collected from 65 NASA astronauts. Several findings emerged from these data. Five personality subscales were related to effectiveness in one form or another. They were: high Negative Expressivity and Negative Communion (subordinate and gullible), low Impatience and Irritability, low Openness (to new ideas and experiences), low Negative Instrumentality (egoism) and high Agreeableness. Examining the graphs of these relationships indicated that they were not linear. This examination indicated that high levels on these undesirable personality characteristics (e.g., Impatience/Irritability) were distributed across all levels of effectiveness. Low levels of the undesirable personality characteristics were found only among the most effective astronauts. We concluded that these other-directed personality qualities will assume increasing importance in long-term spaceflight, and consequently, should be the focus of greater attention in future astronaut selection and training.

Adult↗
PubMed1993

Concurrent infection of human macrophages with HIV-1 and Mycobacterium avium results in decreased cell viability, increased M. avium multiplication and altered cytokine production.

The effects of a concurrent HIV-1 and Mycobacterium avium infection in vitro were assessed in human peripheral blood-derived macrophages (M phi). M phi were infected with HIV-1Ba-L strain for 14 days then infected with M. avium (HIV/M. avium) or treated with LPS (HIV/LPS). At various times after M. avium or LPS treatment, Mo phi cultures were harvested for quantitation of HIV and M. avium replication, as well as M phi cellular viability. In addition, mRNA and supernatants were collected for assessment of induction of the cytokines TNF-alpha, IL-1 beta and IL-6. M. avium multiplication was greater in HIV-infected M phi, whereas no difference in virus production, based on p24 and RT values, was observed between HIV-infected cells and HIV/M. avium or HIV/LPS M phi. M. avium infection of HIV-1-infected M phi also caused a decrease in viability of the M phi. HIV-1/M. avium-infected M phi had a 24 h delay in induction of TNF-alpha steady state mRNA when compared with HIV/LPS or M. avium only or LPS-only treated M phi. HIV infection also increased the amount and the length of induction of IL-1 beta and IL-6 steady state mRNA stimulated by either M. avium or LPS. In addition, prolonged and increased protein production of TNF-alpha, IL-6, and IL-1 beta was observed in HIV/M. avium-infected cells when compared with the other treatments. In direct contrast to M. avium infection, no significant differences in LPS-induced protein production of the three cytokines was observed between HIV-1-infected and -noninfected M phi. Treatment of HIV/M. avium-infected cells with human rGM-CSF did not increase either the time or quantity of induction of TNF-alpha mRNA or protein production in HIV/M. avium-infected M phi. The increase in M. avium numbers, dysregulation of cytokine production, and subsequent cell death seen in vitro in HIV/M. avium-infected human M phi may reflect part of the underlying cause of the highly disseminated M. avium disease pattern observed in AIDS patients.

Cell Survival↗
PubMed1993

Assessments of astronaut effectiveness.

This study examined the reliability and convergent validity of three methods of peer and supervisory ratings of the effectiveness of individual NASA astronauts and their relationships with flight assignments. These two techniques were found to be reliable and relatively convergent. Seniority and a peer-rated Performance and Competence factor proved to be most closely associated with flight assignments, while supervisor ratings and a peer-rated Group Living and Personality factor were found to be unrelated. Results have implications for the selection and training of astronauts.

Aerospace Medicine↗
PubMed1993

Results of a structured psychiatric interview to evaluate NASA astronaut candidates.

One hundred six astronaut applicants who had passed initial screening were evaluated for Axis I and Axis II DSM-III-R diagnoses using a structured psychiatric interview. Nine of 106 candidates (8.5%) met diagnostic criteria for six Axis I (including V-code), or Axis II disorders. The use of the NASA structured interview was effective in identifying past and present psychopathology in a group of highly motivated and healthy astronaut applicants. This was the first time that a structured interview had been used in such a setting for this purpose. The methodology described is applicable to any situation where the presence or history of psychopathology requires evaluation for job selection (e.g. pilot selection).

Aerospace Medicine↗
PubMed1992

Glucocorticoid receptor binding in three different cell types in major depressive disorder: lack of evidence of receptor binding defect.

1. In order to further understand the apparent glucocorticoid resistance in major depressive disorder, circadian variation in cortisol concentration, dexamethasone suppression and glucocorticoid receptor binding in mononuclear leukocytes, polymorphonuclear leukocytes and cultured skin fibroblasts were measured in rigidly defined major depressive disorder patients and non-depressed psychiatric controls. 2. Mononuclear leukocytes binding to glucocorticoid correlated significantly with polymorphonuclear leukocytes binding to glucocorticoid, but both determinations failed to differentiate major depressive disorder and control subjects. 3. Initial and post-dexamethasone in vitro fibroblast binding to glucocorticoid was not different between major depressive disorder and non-depressed control subjects. 4. The phenomenon of glucocorticoid resistance in major depressive disorder remains unexplained.

Adult↗
PubMed1992

Lipid content of alveolar lining material collected by bronchoalveolar lavage. Improved methods for measuring the major lipid classes.

Current methods for measuring lung lipids obtained by bronchoalveolar lavage are time consuming and require sample extraction with organic solvents. Here we utilized enzymatic methods for measuring the major phospholipid classes found in human bronchoalveolar lavage fluid (BALF), namely phosphatidylcholine and phosphatidylglycerol, as well as the neutral lipid cholesterol. These assays can be carried out on as little as 200 microliters lavage fluid in 96-well microtiter plates without the need for organic solvents. Results were verified by comparison with HPLC and chemical methods. The measured values by all three methods were in agreement with previous studies in which lipid analysis was performed by thin-layer chromatography. By contrast to thin-layer chromatography, however, the methods described here can be efficiently performed with small quantities of material without sacrificing accuracy. This methodology can facilitate the characterization of the major surfactant-associated lipids in BALF and foster improved understanding of the role of these lipids in human lung disease.

Bronchoalveolar Lavage Fluid↗
PubMed1992

Characterization of colony stimulating factor activity in the human respiratory tract. Comparison of healthy smokers and nonsmokers.

The number and function of pulmonary macrophages are critical to lung homeostasis. To characterize factors normally present in the human respiratory tract that can influence these parameters, bronchoalveolar lavage (BAL) fluid obtained from healthy smokers and nonsmokers was assayed for the presence of colony-stimulating factor (CSF) activity. Concentrated BAL fluid from both populations was capable of inducing incorporation of [3H]thymidine by murine macrophages. The mean increase (+/- SEM) in incorporation over control cultures not exposed to BAL fluid was 0.98 +/- 0.22 for nonsmokers and 2.25 +/- 1.19 for smokers (p less than 0.001). This CSF bioactivity was characterized as macrophage-CSF (M-CSF) by virtue of its action on murine macrophages, the detection of M-CSF protein by a specific ELISA assay, and the inability to detect other macrophage-active CSFs, granulocyte macrophage-CSF (GM-CSF) and interleukin-3 (IL-3), in a proliferation assay employing the MO7E cell line. There was a significant correlation between macrophage number in BAL samples and measureable bioactivity among both smokers and nonsmokers (r = 0.763; p less than 0.001). This suggested that macrophages themselves are a source of the M-CSF detected in BAL fluid. To examine this possibility, slot-blot analysis of macrophage RNA was performed. Constitutive expression of comparable amounts of M-CSF mRNA and protein was found in cells from both smokers and nonsmokers. However, macrophages obtained from a randomly selected subset of four smokers but none of five nonsmokers exhibited increased production of M-CSF in response to an inflammatory stimulus, lipopolysaccharide (LPS; 5 ng/ml). M-CSF added to macrophage cultures was degraded by nonsmokers' cells as expected over 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The effect of aerosolized recombinant human granulocyte macrophage colony-stimulating factor on lung leukocytes in nonhuman primates.

The number and function of myeloid cells in the lungs are critical determinants of health and disease. To examine whether these cells can be modulated in vivo by a colony-stimulating factor (CSF), recombinant human granulocyte macrophage-CSF (GM-CSF) was given to cynomolgus monkeys by either continuous intravenous infusion (7,200 U/kg/day) for 2 wk or by aerosol exposure to 10(7) U on 1 or 2 consecutive days. At intervals after the initiation of GM-CSF administration, animals underwent bronchoalveolar lavage (BAL) and had peripheral blood sampled to characterize changes in lung and circulating phagocytic cells. Compared with animals exposed to bovine serum albumin, there was an increase in the total number of BAL cells retrieved. This increase was greatest in animals receiving aerosolized GM-CSF, and it was the result of more macrophages and neutrophils. Both lung macrophages and blood neutrophils from animals exposed to aerosolized GM-CSF exhibited an augmented respiratory burst in response to phorbol myristate acetate. Lung macrophages from GM-CSF-exposed animals exhibited increased capacity to bind and/or ingest opsonized and unopsonized Staphylococcus aureus. Despite functional activation of lung phagocytic cells, biochemical analyses of BAL fluid for markers of lung injury revealed an increase in only some parameters in the GM-CSF group. Intravenous administration of GM-CSF had the expected effect on augmenting the number of myeloid cells in the bloodstream. Aerosolized GM-CSF produced a transient effect on circulating myeloid cell number between 3 and 5 days after exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1991

Uptake of Pneumocystis carinii mediated by the macrophage mannose receptor.

Human exposure to Pneumocystis carinii is common but, in the absence of acquired or genetic dysfunction of either cellular or humoral immunity, exposure rarely leads to illness. Although alveolar macrophages can degrade P. carinii, macrophage receptors involved in P. carinii recognition have not been clearly defined. Characterization of a predominant surface glycoprotein of the high mannose type led us to investigate the role of the macrophage mannose receptor in this process. We report here that binding and uptake of cultured rat P. carinii by human and rat alveolar macrophages is reduced by 90% in the presence of competitive inhibitors of mannose receptor activity and by adherence of alveolar macrophages to mannan-coated surfaces. Further, only those COS cells transfected with the human macrophage mannose receptor complementary DNA that express surface mannose receptors bind and ingest P. carinii. These studies establish that the macrophage mannose receptor is sufficient for uptake of P. carinii and emphasize the role of the alveolar macrophage in first-line host defence against P. carinii.

Animals↗
PubMed1991

Infiltration of the lower respiratory tract by helper/inducer T lymphocytes in HTLV-1-associated adult T-cell leukemia/lymphoma.

The human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATLL), a disorder in which peripheral blood and multiple organs are infiltrated by malignantly transformed T lymphocytes. We investigated the nature of pulmonary disease in a patient with serologic evidence of HTLV-1 infection. In this case, endobronchial biopsy specimens showed infiltration of the bronchial mucosa by pleomorphic cells exhibiting a high degree of nuclear irregularity. These cells were morphologically identical in appearance to malignant cells found in peripheral blood and infiltrating the dermis, expressed the OKT4/Leu3 phenotype and the receptor for interleukin 2, and, by analogy to gene rearrangement studies on leukemic blood cells, were monoclonal in origin. However, in situ hybridization of endobronchial biopsy specimens with full-length HTLV-1 probes failed to detect retroviral RNA or proviral DNA. These studies indicate that T lymphocytic involvement of the lower respiratory tract in HTLV-1-associated ATLL is characterized by expression of a malignant phenotype despite the inability to document actual cellular infection with this retrovirus by a molecular hybridization technique.

Adult↗