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Biomedical subjects

R M Rose

Publications and source records attributed to R M Rose.

At least 55 records · Page 3Linked to original sources
PubMed1991

The HIV core protein p24 inhibits interferon-gamma-induced increase of HLA-DR and cytochrome b heavy chain mRNA levels in the human monocyte-like cell line THP1.

Cells from the human monocytic cell-line THP1 were incubated prior to activation with IFN-gamma or LPS with varying amounts of p24, the main product of the HIV gag gene and the major component of the virus core. The IFN-gamma-dependent increase of mRNA for HLA-DR and for the heavy chain of cytochrome b was markedly decreased by p24 but not by gp120. This effect was abrogated by anti-p24 antibodies. On the other hand, preincubation of THP1 cells with p24 did not affect the accumulation of the LPS-dependent mRNA for TNF alpha and IL1-beta. These results indicate that p24 at concentrations similar to those found in the serum of HIV-infected individuals specifically affects IFN-gamma-induced activation markers.

Blotting, Northern↗
PubMed1991

Frequent identification of HIV-1 DNA in bronchoalveolar lavage cells obtained from individuals with the acquired immunodeficiency syndrome.

Tissue macrophages are recognized as a cellular target for infection with the human immunodeficiency virus type 1 (HIV-1). To characterize the nature of this cell-retrovirus interaction within the lower respiratory tract we analyzed fluid and cells obtained by bronchoalveolar lavage (BAL) of eight individuals with acquired immunodeficiency syndrome (AIDS) who were undergoing diagnostic fiberoptic bronchoscopy. Of these eight individuals, seven had active infection with Pneumocystis carinii; one had suspected cytomegalovirus pneumonitis. At the time of study two were receiving the antiretroviral drug zidovudine (azidothymidine [AZT]). HIV-1 could not be isolated from any of the eight samples of BAL fluid concentrated by ultracentrifugation through 20% sucrose. HIV-1 antigen (p24) was detected in one of eight samples of concentrated BAL fluid but could not be found in eight samples of media conditioned by overnight incubation with adherent BAL cells. Despite the infrequent detection of HIV-1 antigen it was possible to identify HIV-1 genomic sequences by the use of a DNA amplification technique, the polymerase chain reaction, in all eight BAL cell preparations. In BAL cells adherent for up to 5 days in culture this method detected retroviral DNA that hybridized to a complementary pair of primers located in the env and gag gene regions of HIV-1. These studies demonstrate the uniform presence of HIV-1 harboring cells within the airways of the lung in individuals with AIDS and active respiratory infection and may have implications for local organ defense.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1991

Increased recovery of surfactant protein A in AIDS-related pneumonia.

Respiratory infection with Pneumocystis carinii (PC) is the most frequent serious opportunistic infection in the clinical setting of acquired immunodeficiency syndrome (AIDS). The factors responsible for the predisposition of human immunodeficiency virus (HIV)-infected patients for PC infection are not fully understood. We postulated that changes in the alveolar lining material (ALM) could play a role in the pathogenesis of PC infection in AIDS. We have compared constituents of ALM in bronchoalveolar lavage fluid from normal, nonsmoking volunteers with that of HIV-infected patients with pneumonia. Using an ELISA, we found that surfactant protein A (SP-A) was markedly elevated in the pneumonia patients. Mean SP-A values for the normal nonsmoking individuals (n = 21) were 1.50 +/- 0.25 micrograms/ml (mean +/- SEM). SP-A levels in the HIV-infected patients (n = 22) were significantly elevated (p less than 0.01) with a mean of 5.23 +/- 0.54 micrograms/ml. This increase was greatest in the patients with more clinically severe pneumonia. The increase in SP-A did not appear to be pathogen-specific as it was also observed in cases of non-PC pneumonia. We also found that total protein levels were nearly five times higher in the HIV-infected pneumonia patients. These studies indicate that the protein component of the ALM is markedly different from normal in cases of HIV-associated PC and non-PC infection. Further investigation is needed to determine the mechanism of these alterations and their role, if any, in AIDS-related pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Growth inhibition of Mycobacterium avium complex in human alveolar macrophages by the combination of recombinant macrophage colony-stimulating factor and interferon-gamma.

The reservoir of Mycobacterium avium complex (MAC) during human infection is the mononuclear phagocyte. In these studies, the ability of certain macrophage-active cytokines to affect MAC growth in human alveolar macrophages was evaluated. Neither recombinant interferon-gamma (2 x 10(2) to 10(3) U/well of 5 x 10(5) cells) nor recombinant macrophage colony-stimulating factor (20 to 50 ng/well), when tested alone, exhibited a consistent ability to induce macrophage targets to inhibit the growth of a clinical strain of MAC serovar 4. However, the combination of these cytokines (1 to 50 ng macrophage colony-stimulating factor + 10(3) U interferon per well) was remarkably effective in diminishing replication of MAC in all experiments. These cytokines were also able to induce alveolar macrophages to restrict MAC growth even though cells were obtained from several individuals with acquired immunodeficiency syndrome (AIDS) or from normal donors and infected in vitro with the human immunodeficiency virus type 1. The effect of this cytokine combination was not abrogated by 10(4) neutralizing U/ml of anti-tumor necrosis factor-alpha antibody. Rather, the combination of interferon-gamma and macrophage colony-stimulating factor appeared to activate intrinsic macrophage mechanisms for restricting MAC growth and deserves further study to determine the potential value of this cytokine combination in the treatment of human infection.

Cells, Cultured↗
PubMed1991

Immunology of the lung in HIV infection: the pathophysiologic basis for the development of tuberculosis in the AIDS setting.

Active tuberculosis is now recognized as a frequent and serious complication of infection with the human immunodeficiency virus (HIV), the causative agent of AIDS. HIV mediated alteration in host defenses against mycobacteria contribute to the magnitude and severity of this problem. HIV can affect a variety of cellular mechanisms important in the restriction of mycobacterial growth. Qualitative and quantitative defects in T lymphocyte function result from direct HIV infection of cells expressing the CD4 epitope, and can severely limit the production of macrophage activating cytokines capable of inducing an anti-mycobacterial state in cells of monocyte lineage. In addition, macrophages themselves are susceptible to HIV infection, and have been shown to be defective with respect to a variety of host defense functions. Both T4 lymphopenia and HIV infected macrophages are present in the lower respiratory tract of HIV infected individuals, a circumstance which likely underlies the unique susceptibility of HIV infected to tuberculosis.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Effect of zidovudine and granulocyte-macrophage colony-stimulating factor on human immunodeficiency virus replication in alveolar macrophages.

The alveolar macrophage (AM), as a representative human tissue macrophage, was used in an in vitro system to examine the anti-human immunodeficiency virus type-1 (HIV-1) activity of zidovudine (AZT) and granulocyte-macrophage colony-stimulating factor (GM-CSF). AMs were infected with the IIIB strain of HIV-1 and exposed to AZT (1 mumol/L), GM-CSF (30 U/mL), a combination of AZT (1 mumol/L)/GM-CSF (30 U/mL), or medium control. At 10 or 20 days post-infection, phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear leukocytes (PBMLs) were added to the AM cultures as stimulated target cells. AZT effectively suppressed HIV replication and prevented transfer/amplification in target PBMLs as long as the drug was maintained in the medium. GM-CSF neither suppressed nor augmented HIV replication. The combination of AZT/GM-CSF was comparable with AZT alone in suppressing both the initial infection of AMs and the transfer to target PBMLs as long as the agents were maintained in the cultures. However, when the drugs were removed at the same time that PHA-stimulated PBMLs were added to the culture, the combination of AZT/GM-CSF was found to be more effective than AZT alone in preventing the transfer/amplification of HIV in the target lymphocytes. These results suggest that (1) AZT is effective in inhibiting HIV-1 infection in mononuclear phagocytes; (2) GM-CSF neither inhibits nor augments the replication of the IIIB strain of HIV in human AMs; and (3) the combination of AZT and GM-CSF may have an enhanced anti-HIV-1 activity compared with AZT alone. Clinical trials with the two agents in combination appear warranted.

Cells, Cultured↗
PubMed1990

A reduced-modulus acrylic bone cement: preliminary results.

Excessive local contact stress is implicated as an important factor in the initiation of the loosening process after total joint arthroplasties. A reduced-modulus acrylic bone cement, which decreases the bone-cement interface stresses, was developed to test this hypothesis. The formulation consists of butylmethacrylate beads, having a glass transition temperature of 27 degrees C, in a methylmethacrylate matrix. This cement, polybutylmethylmethacrylate (PBMMA), has an elastic modulus one-eighth that of standard PMMA bone cement, 0.27 vs. 2.1 GPa, at body temperature. In vivo use in a pilot study using the sheep total hip arthroplasty model shows a reduction in the rate of loosening of femoral components when compared both radiographically and mechanically with PMMA controls.

Acrylic Resins↗
PubMed1990

The effect of porous coating processing on the corrosion behavior of cast Co-Cr-Mo surgical implant alloys.

The manufacture of porous coated cobalt-based surgical implant alloys requires sintering--a high temperature process above the incipient melting temperature of this alloy system. The metallurgical changes produced by the high temperature sinter cycle consist of dissolution of interdendritic carbides, massive precipitation of lamellar carbide eutectic phases at grain boundaries, localized porosity from incipient melting that is not completely eliminated by subsequent hot isostatic pressing, and grain growth in fine-grained materials. These microstructural changes, which are known to affect the mechanical properties, do not affect the static in vitro localized and generalized corrosion behavior of the bulk material as determined by anodic polarization measurements in a buffered saline environment and direct examination by scanning electron and optical microscopy. Additionally, cast Co-Cr-Mo surgical implant alloys are found to be immune to crevice corrosion (in the absence of mechanical fretting) in the saline environment studied. The hysteretic component of the anodic polarization curve is not due to crevice corrosion; rather, as suggested by the electrochemical tests and Auger spectroscopy, the hysteresis is due to redox reactions in the chromium-rich surface layer.

Bone and Bones↗
PubMed1990

Mononuclear leukocyte glucocorticoid receptor binding characteristics and down-regulation in major depression.

Some patients with major depressive disorder (MDD) have elevated plasma cortisol concentrations and show failure to suppress cortisol secretion upon administration of dexamethasone (DEX), yet they do not have Cushingoid features. To study whether this represents glucocorticoid (GC) resistance, [3H]-DEX-binding assays were used to measure, in vitro, the GC receptor affinity (1/Kd) and number (Bmax) in mononuclear leukocytes of 11 MDD patients and 15 control subjects. No receptor abnormalities were detected in the MDD group; thus any cellular defect leading to a lack of responsiveness to GC in the MDD patients, if present, probably lies beyond the initial receptor binding. DEX (1.0 mg orally) was administered to study in vivo GC receptor down-regulation. Compared to the control group, fewer depressed subjects down-regulated Bmax after DEX. By paired t-test, Bmax decreased significantly in the control group but not in the depressed group. Receptor number on the control day did not correlate significantly with the degree of receptor down-regulation, severity of depression or cortisol concentrations across all the subjects. These results do not lend support to previous reports suggesting that GC resistance in MDD results from a GC receptor-binding abnormality, and they emphasize the importance of considering receptor studies in the context of GC-mediated cell processes in order to identify the exact cellular defect(s) leading to GC resistance.

Administration, Oral↗
PubMed1990

Effects of recombinant soluble CD4 (rCD4) on HIV-1 infection of monocyte/macrophages.

Recombinant soluble CD4 (rCD4) was tested for its ability to block acute human immunodeficiency virus (HIV) infection in the U937 monocytic cell line and in human pulmonary alveolar macrophages (PAM) and for its ability to prevent transfer of virus from chronically infected PAM to target peripheral blood mononuclear leukocytes (PMNL). With an initial virus inoculum of 10(3)-10(4) TCID50/ml, rCD4 completely prevented acute HIV infection of U937 cells at concentrations greater than or equal to 1 microgram/ml and provided substantial but incomplete protection at 0.1 microgram/ml. With an initial virus inoculum of 10(2) TCID50/ml, rCD4 completely prevented acute infection of PAM at concentrations greater than or equal to 0.1 microgram/ml. The transmission of HIV-1 infection to PMNL cocultured with chronically infected PAM was completely inhibited at concentrations greater than or equal to 1 microgram/ml if cell-to-cell contact was prevented. With direct PAM-PMNL contact, substantial inhibition was obtained at an rCD4 concentration of 10 micrograms/ml, and higher concentrations (200 micrograms/ml) could completely block transfer. These results demonstrated that rCD4 can be effective in preventing de novo infection of cells of the monocyte/macrophage lineage, but microenvironments where cell-to-cell contact predominates are likely to pose a formidable challenge to this therapeutic strategy.

CD4 Antigens↗
PubMed1990

Two-, three-, and four-interval forced-choice staircase procedures: estimator bias and efficiency.

Threshold estimates for multiple-interval forced-choice staircase procedures were studied using computer simulations. A sigmoidal psychometric function shape governed the hypothetical subject's responses in the simulations. Parameters varied included the number of trials, the step size for stimulus level change, and decision rules that targeted 70.7% and 79.4% correct performance. Each threshold estimate was calculated by averaging the stimulus levels at which a reversal a stimulus level direction occurred. The results of the simulations suggest that, as the number of alternatives is increased from 2 to 4, the variability of repeated threshold estimates decreases or remains constant, and the accuracy of the estimator, in most cases, improves. A subset of the simulations was compared with data obtained in a detection-in-noise task. The behavioral data were consistent with the simulation results. Two major conclusions were reached. First, 3- and 4-interval forced-choice (IFC) procedures are more efficient than a 2IFC procedure with a decision rule that targets 70.7% correct performance even when the additional time required to complete 3- and 4IFC trials is considered. Second, the accuracy of 2IFC procedures can be improved by fitting the trial history of a staircase run using probit analysis.

Attention↗
PubMed1990

Cell organelle motions in bronchoalveolar lavage macrophages from smokers and nonsmokers.

The migratory and phagocytic capabilities of pulmonary macrophages are important elements in lung defense against particles and pathogens deposited on alveolar surfaces. Both functions rely on macrophage cytoplasmic movements. We examined how a common respiratory exposure, cigarette smoking, affects intracellular motions in human pulmonary macrophages (HPM phi). We observed that HPM phi isolated by bronchoalveolar lavage from human volunteers and cultured in vitro were capable of ingesting unopsonized magnetic iron oxide particles localized within phagosomes and phagolysosomes. Upon magnetization, the particles collectively produced a remanent magnetic field (RMF). Motions of particle-containing organelles caused a decay of the RMF, or "relaxation." We applied this technique, which is an alternative to optical microscopy, for evaluating both movement and viscosity of macrophage cytoplasm. In our in vitro studies, we found that HPM phi isolated from smokers exhibited more rapid RMF decay than did HPM phi isolated from nonsmokers. Rotating the intracellular magnetic particles with external fields showed that the HPM phi cytosol was highly viscous in both smoker and nonsmoker cells. In both cell groups, resistance to particle rotation was increased by 2.6 ng/ml phorbol myristate acetate. Our in vitro magnetometric quantification of intracellular particle movement in isolated HPM phi suggests that lung macrophage cell organelle motions are increased in smokers; this may be the mechanism for the enhanced in vivo magnetic-particle motion reported previously in magnetometric studies of human subjects who are smokers.

Bronchoalveolar Lavage Fluid↗
PubMed1990

In vitro dissolution of uniform cobalt oxide particles by human and canine alveolar macrophages.

Intracellular dissolution of inhaled particles is an important pathway of clearance of potentially toxic materials. To study this process, monolayers of human and canine alveolar macrophages (AM) were maintained alive and functional in vitro for more than 2 wk. Complete phagocytosis of moderately soluble, monodisperse 57Co3O4 test particles of four different sizes was obtained by optimizing the cell density of the monolayer and the particle-to-cell ratio. The fraction of the initial particle mass that was soluble increased over time when the particles were ingested by AM but remained constant when in culture medium alone. Smaller particle sizes had a faster characteristic intracellular dissolution rate constant than did larger particles. The dissolution rates differed between AM obtained from two human volunteers as compared to those obtained from six mongrel dogs. These in vitro dissolution rates were very similar to in vivo translocation rates previously obtained from human and canine lung clearance studies after inhalation of the same or similar monodisperse, homogeneous 57Co3O4 test particles. We believe an important clearance mechanism for inhaled aerosol particles deposited in the lungs can be simulated in vitro in a cell culture system.

Adult↗
PubMed1990

The flow-ratio index. An approach for measuring the influence of age and cigarette smoking on maximum expiratory flow-volume curve configuration.

A forced expiratory flow ratio, derived from the average slope of the maximum expiratory flow-volume (MEFV) curve over a specified volume interval, was examined in healthy asymptomatic cigarette smokers and nonsmokers. This index was developed to have the properties that it would be (1) simple to calculate, (2) less effort dependent than indices that incorporate peak flow, and (3) free of influence from the configurational detail and noise frequently occurring at higher lung volumes on MEFV curves. Forced expired vital capacity maneuvers were performed by participants in a worksite health promotion program. Data from asymptomatic individuals with normal pulmonary function were analyzed for 49 cigarette smokers and 52 nonsmokers; 25 individuals had MEFV curves collected twice over a one-year interval. The ratio of flow derived from an average MEFV slope to instantaneous flow was calculated over the lower half of the vital capacity. Flow ratios were expressed as a percentage of the instantaneous flow at 75 percent of the expired vital capacity (FR75). This ratio was reproducible from year 1 to year 2 (r = 0.86, p less than 0.0001). Furthermore, the FR75 was well correlated with age among cigarette smokers and nonsmokers (r = 0.68 and 0.63 respectively). The slope of the least squares regression equation relating FR75 to age was significantly greater among smokers than nonsmokers (2.90 percent per year vs. 1.73 percent per year, p less than 0.025). While there was a significant interactive influence of age and total pack-years on the FR75 (F = 2.91, p = 0.02), this index did not differ systematically by gender. We conclude that the FR25 is a more sensitive index of altered lung function in cigarette smokers than are results of conventional pulmonary function.

Adult↗
PubMed1990

Anomie, alcohol abuse and alcohol consumption: a prospective-analysis.

Cross-sectional and 36-month prospective analyses of the relationships among anomie and both alcohol abuse and alcohol consumption patterns provided little support that anomie was directly associated with ethanol ingestion patterns in a sample of 302 male air traffic controllers. This lack of association was observed for self-reported alcohol consumption, interview-established alcohol abuse and biochemical markers of alcohol intake. In addition, anomie was not predictive of change in alcohol use/abuse over 36 months, controlling for baseline levels of alcohol use and abuse and for relevant demographic factors. Measurement of anomie and alcohol use/abuse, the relative importance of anomie in various socioeconomic groups and issues related to prospective research on this topic are discussed.

Adult↗
PubMed1990

A prognosis for ultra high molecular weight polyethylene.

Ultra high molecular weight polyethylene (UHMPWE) is now the material of choice for total joint replacement prostheses, in combination with a metal surface against which the polymer articulates. As this material has now been in use in this application for approximately three decades and other limiting factors (e.g. loosening of the prosthesis) have been improved upon, it is appropriate to attempt a long-term prognosis.

Joint Prosthesis↗
PubMed1989

The assembly of ionic currents in a thalamic neuron. I. The three-dimensional model.

We have previously discussed qualitative models for bursting and thalamic neurons that were obtained by modifying a simple two-dimensional model for repetitive firing. In this paper we report the results of making a similar sequence of modifications to a more elaborate six-dimensional model of repetitive firing which is based on the Hodgkin-Huxley equations. To do this we first reduce the six-dimensional model to a two-dimensional model that resembles our original two-dimensional qualitative model. This is achieved by defining a new variable, which we call q. We then add a subthreshold inward current and a subthreshold outward current having a variable, z, that changes slowly. This gives a three-dimensional (v,q,z) model of the Hodgkin-Huxley type, which we refer to as the z-model. Depending on the choice of parameter values this model resembles our previous models of bursting and thalamic neurons. At each stage in the development of these models we return to the corresponding seven-dimensional model to confirm that we can obtain similar solutions by using the complete system of equations. The analysis of the three-dimensional model involves a state diagram and a stability diagram. The state diagram shows the projection of the phase path from v,q,z space into the v,z plane, together with the projections of the curves z = 0 and v = q = 0. The stability of the points on the curve v = q = 0, which we call the v, q nullcurve, is determined by the stability diagram. Taken together the state and stability diagrams show how to assemble the ionic currents to produce a given firing pattern.

Animals↗