Biomedical subjects

R M Rose

Publications and source records attributed to R M Rose.

At least 19 recordsLinked to original sources

PubMed2002

Food concentration affects the life history response of Ceriodaphnia cf. dubia to chemicals with different mechanisms of action.

The effect of three chemicals with different mechanisms of action (3,4-dichloroaniline, fenoxycarb, and chlorpyrifos) on the life history response of the cladoceran Ceriodaphnia cf. dubia was examined under both limited (3 x 10(4) cells/mL) and abundant (15 x 10(4) cells/mL) food conditions. Toxicity tests were conducted at both food concentrations simultaneously for each chemical, and cladocerans were examined daily from less than 24 h old until their death. A range of life history parameters were calculated, including mean brood sizes, survival, net reproductive rate, and population growth rate. The toxicity of 3,4-dichloroaniline was not significantly affected by food concentration. However, limited food significantly decreased the toxicity of fenoxycarb, and significantly increased the toxicity of chlorpyrifos. The effect of food concentration on toxicity appears to depend on the mechanism by which the chemical exerts its toxicity and on food--chemical interactions. Possible mechanisms for the different effects of food concentration on toxicity are discussed.

Aniline Compounds↗

PubMed2001

Depression and work productivity: the comparative costs of treatment versus nontreatment.

This article discusses the impact of depression on work productivity and the potential for improved work performance associated with effective treatment. We undertook a review of the literature by means of a computer search using the following key terms: cost of illness, work loss, sickness absence, productivity, performance, and disability. Published works were considered in four categories: (1) naturalistic cross-sectional studies that found greater self-reported work impairment among depressed workers; (2) naturalistic longitudinal studies that found a synchrony of change between depression and work impairment; (3) uncontrolled treatment studies that found reduced work impairment with successful treatment; and (4) controlled trials that usually, but not always, found greater reduction in work impairment among treated patients. Observational data suggest that productivity gains following effective depression treatment could far exceed direct treatment costs. Randomized effectiveness trials are needed before we can conclude definitively that depression treatment results in productivity improvements sufficient to offset direct treatment costs.

Absenteeism↗

PubMed2001

The presence of chemicals exuded by fish affects the life-history response of Ceriodaphnia cf. dubia to chemicals with different mechanisms of action.

The toxicity of chemicals with different mechanisms of action (3,4-dichloroaniline, fenoxycarb, and chlorpyrifos) to the cladoceran Ceriodaphnia cf. dubia was examined in the presence and absence of chemicals exuded by fish, termed fish kairomones. A range of life-history traits were examined, including mean brood sizes, survival, net reproductive rate (Ro) and population growth rate (r). Cladocerans exposed to 3,4-dichloroaniline showed similar sensitivities in the presence and absence of fish kairomones with respect to all of the life-history traits examined. The presence of fish kairomones reduced the sensitivity of cladocerans to fenoxycarb with respect to mean brood sizes and r but increased their sensitivity in terms of Ro. The presence of fish kairomones increased the sensitivity of cladocerans to chlorpyrifos with respect to survival, r, Ro, and mean brood sizes. The general trends observed were similar to those shown when C. cf. dubia was exposed to these chemicals under low food conditions, and it is suggested that the effects of fish kairomones on toxicity may be attributed to the reduction in feeding rates observed when C. cf. dubia is exposed to fish kairomones.

Aniline Compounds↗

PubMed2000

Randomized, placebo-controlled pilot study of divalproex sodium in the treatment of acute exacerbations of chronic schizophrenia.

Experimental and clinical data suggest that GABA-ergic drugs such as valproate may have a potential role in the treatment of schizophrenia. The authors designed a 21-day prospective, double-blind, randomized, placebo-controlled pilot study of divalproex sodium as add-on treatment to haloperidol in 12 hospitalized patients with acute exacerbations of chronic schizophrenia. All patients received haloperidol 10 mg/day for 3 days and 15 mg/day for the remaining 18 days. In addition, five patients were randomly assigned to receive divalproex augmentation and seven to receive placebo. The divalproex dose was adjusted to a target serum concentration of 75 microg/mL for 2 weeks; placebo replaced divalproex during the third and last weeks to determine any carryover effect. Psychiatric rating scales were administered at baseline and on days 7, 14, and 21. Although the placebo group improved with haloperidol treatment, the divalproex group demonstrated greater improvement. On day 21, the divalproex group had greater improvement from baseline on the Clinical Global Impression Scale (p < or = 0.04), Brief Psychiatric Rating Scale (p < or = 0.13), and Schedule for Assessment of Negative Symptoms scores (p < or = 0.007). After divalproex withdrawal on day 15, a carryover effect was observed during week 3. The authors concluded that the addition of divalproex sodium to standard antipsychotic drugs may prove effective in relieving the symptoms of acute schizophrenia. Future studies may benefit from the design of this pilot study. However, it is premature to apply this augmentation strategy in the clinical setting just yet because of the small sample size and the likely heterogeneity of the disorder.

Acute Disease↗

PubMed2000

Alveolar macrophages from human immunodeficiency virus-infected persons demonstrate impaired oxidative burst response to Pneumocystis carinii in vitro.

The alveolar macrophage (AM) oxidative burst response is an important component of microbicidal effector cell function against a variety of potential pathogens in the lungs, although the role against Pneumocystis carinii has not been fully investigated. The goals of this study were to characterize the P. carinii-mediated oxidative burst of AMs from healthy individuals, and to examine the oxidative burst of AMs from human immunodeficiency virus (HIV)-infected persons. For healthy individuals, the AM oxidative burst (measured as hydrogen peroxide [H(2)O(2)] production) increased in a time- and concentration-dependent manner in response to P. carinii or to the major surface glycoprotein of P. carinii, gp-A (0.01 to 10 microg/ml), required physical contact of P. carinii with AMs, and was not dependent on organism viability. Enzymatic removal of the surface-associated molecules of P. carinii reduced the oxidative burst to 43% of control (P = 0.01). Blocking the AM mannose receptor reduced the P. carinii-mediated oxidative burst response to 37% of control (P = 0.01). Compared with AMs from healthy individuals, P. carinii-mediated H(2)O(2) production was significantly reduced in AMs from asymptomatic HIV-positive (HIV+) persons with CD4+ counts < 200 cells/mm(3) (249+/-43 relative fluorescence units [RFU] versus 130+/-44 RFU; mean +/- standard error of the mean, P = 0.038) and HIV+ persons with active P. carinii pneumonia (78+/-40 RFU; P = 0.014), but preserved for HIV+ persons with CD4+ counts > 200 cells/mm(3). Importantly, H2O2 production in response to phorbol myristate acetate or serum-opsonized zymosan particles was preserved in all groups studied. Thus, AM oxidative burst, mediated in part via P. carinii gp-A and AM mannose receptor may represent an important host response to P. carinii. A specific impairment of P. carinii-mediated AM oxidative burst in persons with advanced HIV infection may contribute to the pathogenesis of P. carinii pneumonia.

Animals↗

PubMed1999

Critical review of GABA-ergic drugs in the treatment of schizophrenia.

GABA-ergic medications may have a potential role in the treatment of schizophrenia. Laboratory evidence has generally supported the ability of gamma-aminobutyric acid (GABA) to reduce dopaminergic activity and has suggested that GABA may be effective in combating hypofrontality by acting on mesoprefrontocortical tracts in patients resistant to treatment with antipsychotic drugs. Although the results of clinical trials of several GABA-ergic compounds have been inconclusive because of methodologic limitations and drug toxicity, benzodiazepines and valproate seem to be associated with favorable treatment outcomes, especially when combined with typical antipsychotic agents. This study concludes that further investigation of the use of GABA in schizophrenia is likely to improve the understanding of the psychopathology of this illness and to expand our treatment alternatives. Also provided are suggestions to enhance the design of future studies, improve the potential for favorable treatment outcomes, and assist in predicting patients' responses to GABA-ergic medications.

Anti-Anxiety Agents↗

PubMed1998

Reduced binding and phagocytosis of Pneumocystis carinii by alveolar macrophages from persons infected with HIV-1 correlates with mannose receptor downregulation.

The macrophage mannose receptor, a pattern recognition molecule and component of innate immunity, mediates binding and phagocytosis of Pneumocystis carinii and likely represents an important clearance mechanism in the lungs of immunocompetent hosts. The purpose of this study was to examine the ability of alveolar macrophages from HIV-infected individuals to bind and phagocytose P. carinii, and to investigate the role of the macrophage mannose receptor in mediating this interaction. Compared with healthy individuals, alveolar macrophage phagocytosis of P. carinii from HIV+ persons was reduced up to 74% (P = 0.02), primarily reflecting a reduction in the number of organisms associated with each macrophage (P = 0.019). Furthermore, macrophages from HIV+ individuals demonstrated up to an 80% (P < 0.05) reduction in mannose receptor surface expression and endocytosis. Mannose receptor affinity was unaltered, and mRNA levels were modestly reduced (P < 0.05). Cells from HIV+ individuals with CD4(+) counts < 200 cells/mm3 (representing individuals at high clinical risk for P. carinii pneumonia) demonstrated the lowest levels of P. carinii phagocytosis and mannose receptor endocytosis. In vitro HIV infection of alveolar macrophages from healthy individuals reduced mannose receptor endocytosis to 53.2% (P < 0.05) and P. carinii binding and phagocytosis to 67.4% (P < 0.05) of control. Our studies suggest that HIV infection may alter innate immunity in the lungs, and that impaired alveolar macrophage mannose receptor-mediated binding and phagocytosis of P. carinii may contribute to the susceptibility of HIV-infected individuals to this opportunistic pulmonary pathogen.

Bronchoalveolar Lavage Fluid↗

PubMed1998

Surfactant protein-A reduces binding and phagocytosis of pneumocystis carinii by human alveolar macrophages in vitro.

Surfactant protein-A (SP-A) levels are increased in Pneumocystis carinii pneumonia, but the role of SP-A in the pathogenesis of P. carinii pneumonia is not completely understood. This study investigated the effect of SP-A on the in vitro binding and phagocytosis of P. carinii by normal human alveolar macrophages (AM). Determination of binding and phagocytosis was done with a fluorescence-based assay, utilizing fluorescein isothiocyanate (FITC)-labeled P. carinii. Binding and phagocytosis of P. carinii to AM correlated inversely with the levels of SP-A present on the surface of the organisms (r = -0.6323, P = 0.0086; and r = -0.9827, P < 0.0001, respectively). The addition of exogenous SP-A to organisms with low surface-associated SP-A reduced P. carinii binding by 30% (P < 0.05) and reduced phagocytosis by 20% (P < 0.05), whereas this effect was reversed with ethylenediamine tetraacetic acid (EDTA) or anti-SP-A antibody. Furthermore, binding and phagocytosis were enhanced after enzymatic removal of P. carinii surface-associated SP-A, and this effect was reversed with the addition of exogenous SP-A. The observed inhibitory effect of SP-A on P. carinii binding and phagocytosis reflected binding of SP-A to the organisms rather than a direct effect of SP-A on the macrophages. These data suggest that increased levels of SP-A may contribute to the pathogenesis of P. carinii pneumonia through binding to the surface of the organism and interfering with AM recognition of this opportunistic pulmonary pathogen.

Candida albicans↗

PubMed1996

Administration of an antibody to E-selectin in patients with septic shock.

OBJECTIVES: To determine the safety and pharmacokinetics of a murine monoclonal antibody to E-selectin in patients with newly developed septic shock. DESIGN: Open-label, prospective, phase II pilot study with escalating doses of the antibody. SETTING: Intensive care unit of a 900-bed university hospital. PATIENTS: Nine patients who survived the first 24 hrs of septic shock. INTERVENTIONS: In addition to standard therapy, an intravenous bolus of a murine monoclonal antibody to E-selectin, CY1787, was given at doses of 0.1 mg/kg (n = 3), 0.33 mg/kg (n = 3), and 1.0 mg/kg (n = 3). MEASUREMENTS AND MAIN RESULTS: CY1787 was well tolerated in all patients. Signs of shock resolved in all patients, and organ failure entirely reversed in eight patients. All patients survived the 28-day follow-up. Administration of CY1787 was associated with an early and brisk increase in PaO2/FIO2 ratio (p < .001), from 146 +/- 38 mm Hg (19.5 +/- 5.1 kPa) to 205 +/- 45 mm Hg (27.3 +/- 6.0 kPa) after 2 hrs, and 250 +/- 58 mm Hg (33.3 +/- 7.7 kPa) after 12 hrs. A dose-related effect of CY1787 was suggested by an earlier weaning from catecholamine therapy and a faster resolution of organ failure in the high-dose group. Development of antimouse antibodies was documented in eight patients. CONCLUSIONS: This pilot study indicates that this antibody to E-selectin appears to be safe and may represent a promising form of therapy in septic shock.

Adult↗

PubMed1996

Elevated selectin levels after severe trauma: a marker for sepsis and organ failure and a potential target for immunomodulatory therapy.

UNLABELLED: Severe injury is frequently complicated by sepsis and organ failure. Activated neutrophils adherent to inflamed endothelia have been implicated in the pathogenesis of these complications. Identification of high-risk patients to target immunomodulatory therapy, however, remains an elusive goal. We postulated that (1) patients at risk for sepsis and organ failure could be identified by measuring shed selectin adhesions molecules as a marker of endothelial activation after injury and reperfusion, and (2) these elevated selectin levels would correlate with injury severity, shock, major complications, and mortality. METHODS: Blood samples were drawn from 50 patients with multiple trauma every 2 hours after admission for the first 24 hours, and every 6 hours for the subsequent 24 hours, and assayed for levels of shed E- and P-selectin. Patients were then stratified according to Injury Severity Score (ISS), presence or absence of shock, presence or absence of organ failure and/or infectious complications, and finally, death versus survival. RESULTS: Trauma patients who had ISS < 30, who did not develop shock, sepsis, or organ dysfunction, had minimal increase in circulating E- and P-selectin over admission levels. In patients who subsequently developed infectious complications, organ dysfunction, or both, or subsequently went on to die, elevated levels of E-selectin levels were evident by 36 hours, and in some cases, earlier. Differences between nonsurvivors and survivors was statistically significant. There was also a trend toward increased levels of P-selectin in the same group of patients, although these differences were not significant. There was no differentiation in either of the two selections when patients were stratified according to ISS or presence of shock. CONCLUSION: A subset of major trauma patients manifest increased levels of circulating E-selectin adhesion molecules after resuscitation. These patients seem to be at increased risk of death and possibly at risk for infections complications and organ failure. Selectin blockade is a potential new immunomodulatory strategy in this subgroup of patients.

Adjuvants, Immunologic↗

PubMed1996

Surfactant protein-A levels increase during Pneumocystis carinii pneumonia in the rat.

In bronchoalveolar lavage (BAL) of human immunodeficiency virus (HIV)-infected patients with Pneumocystis carinii pneumonia and in lungs of glucocorticoid-immunosuppressed rats infected with P. carinii, surfactant phospholipid levels are reduced. However, levels of the surfactant-associated protein-A (SP-A) in BAL are 4-5 times higher than normal in patients with P. carinii pneumonia. In this study, we examined the effects of glucocorticoid immunosuppression and P. carinii infection on SP-A messenger ribonucleic acid (mRNA) and protein levels in rat lungs. Rats were immunosuppressed by adding dexamethasone to their drinking water and were infected with P. carinii by intratracheal instillation of the organism. SP-A was measured by enzyme-linked immunosorbent assay (ELISA) and SP-A mRNA by hybridization of Northern blots with an SP-A complementary deoxyribonucleic acid (cDNA) probe. There was a severalfold increase in SP-A protein and mRNA levels in uninfected glucocorticoid-treated rats. However, contrary to what has been reported with the surfactant-associated lipids, SP-A mRNA and protein levels in P. carinii-infected animals were significantly higher than those found in the uninfected, immunosuppressed animals. Our results demonstrate that SP-A increases, probably as a result of elevated mRNA levels, in immunosuppressed rats with P. carinii infection and are consistent with our findings in HIV-positive patients with P. carinii pneumonia.

Animals↗

PubMed1996

Fatigue strength of polyethylene after sterilization by gamma irradiation or ethylene oxide.

The oxidation level of ultrahigh molecular weight polyethylene specimens sterilized by gamma irradiation in either air or Ar gas was compared with that of unsterilized and ethylene oxide sterilized ultrahigh molecular weight polyethylene. The fatigue strength of ultrahigh molecular weight polyethylene specimens sterilized by gamma irradiation in air was compared with that of unsterilized and ethylene oxide sterilized ultrahigh molecular weight polyethylene. At the specimen surface, oxidation was highest for ultrahigh molecular weight polyethylene gamma irradiated in air, lower for ultrahigh molecular weight polyethylene gamma irradiated in Ar gas, and absent in unsterilized and ethylene oxide sterilized ultrahigh molecular weight polyethylene. At a depth of 3.5 mm below the specimen surface, oxidation levels were equivalent for ultrahigh molecular weight polyethylene gamma irradiated in either air or Ar gas whereas unsterilized and ethylene oxide sterilized specimens were again unoxidized. Thus, even in an inert atmosphere, oxidative degradation of gamma irradiated ultrahigh molecular weight polyethylene occurs. The 10 million cycle fatigue strength was similar for unsterilized and ethylene oxide sterilized ultrahigh molecular weight polyethylene whereas the fatigue strength of gamma irradiated in air ultrahigh molecular weight polyethylene was lower. Results of this study show that ethylene oxide gas does not degrade ultrahigh molecular weight polyethylene whereas gamma radiation in air causes changes in the polymer that adversely affect its mechanical properties. Ethylene oxide gas is a viable alternative to gamma radiation in air that avoids oxidation and fatigue strength degradation known to accompany irradiation of ultrahigh molecular weight polyethylene polymer bearing surfaces in total joint implants.

Biophysical Phenomena↗

PubMed1995

Quantitative culture of HIV-1 from bronchoalveolar lavage cells.

Determination of the infectious virus burden at the organ level is critical for understanding the pathophysiology of human immunodeficiency virus type 1 (HIV-1) infection. To evaluate the burden of HIV-1 in the lung, quantitative cultures were performed on bronchoalveolar lavage (BAL) cells from 11 HIV-1 seropositive subjects without respiratory infections and compared with peripheral blood mononuclear cells (PBMC) obtained from the same subjects. Fifty percent (50%) of subjects had positive BAL cell cultures while 82% had positive PBMC cultures. There was much less virus cultured from BAL cells than from PBMCs, whether using phytohemagglutinin (PHA)-stimulated peripheral blood lymphocyte (PBL) targets (p < 0.05) or adherent monocyte targets (p < 0.02). There was no significant difference between the HIV-1 titers obtained for BAL cells whether using PHA-stimulated PBL or adherent monocyte targets (p = 0.13). These studies demonstrate that BAL cell cultures for HIV-1 in subjects without respiratory infections are less frequently positive than PBMC cultures, that less virus can be recovered from BAL cells than from PBMC, and that HIV-1 isolates from BAL cells replicate in both PHA-stimulated PBL targets and adherent monocyte targets. Quantitative assessment of virus burden in the lung is important for future studies of HIV-1 pathogenesis and for evaluating potential antiretroviral therapies aimed at altering the natural history of organ dysfunction associated with retroviral replication.

Adult↗

PubMed1995

Use of personal characteristics in the selection of astronauts.

Which personal characteristics are used in selecting astronauts? We decided to examine this question using National Aeronautics and Space Administration (NASA) archival data collected on 2288 applicants. Undergraduate grade point average, graduate grade point average, and several facets of aviation experience were the best predictors of who was interviewed and then selected to be an astronaut. Adjustments were made to insure that a sufficient number of women and minority group members were selected, while still maintaining high selection standards. The selection process seems well-designed, and follows explicit NASA guidelines. We suggest simplifying the selection process by using a single discriminant function as an interview and/or selection criterion.

Astronauts↗

PubMed1994

A model for rebound bursting in mammalian neurons.

In this paper we begin by simplifying our previous model of a thalamic neuron (Rose & Hindmarsh Proc. R. Soc. Lond. B 237, 289-312 (1989b)) by removal of the A current. A Ca(2+)-activated K+ current, with Ca2+ entering through T channels, is then added to give a model for a class of mammalian neurons in which the membrane potential oscillates in the subthreshold region following a hyperpolarizing current step. The properties of the model are represented using an experimentally observable bifurcation diagram. In the subthreshold region only three variables are required to explain the essential dynamic properties of the cell. In this three-dimensional space the solutions tend to lie on a surface which resembles a paraboloid. We use a simplified model of this model to explain both the dynamics of the solutions on this surface and the form of the bifurcation diagram.

Animals↗

PubMed1994

Resonance in a model of a mammalian neuron.

In this paper we show that for a small range of voltages the model described in the previous paper (Hindmarsh & Rose Phil. Trans. R. Soc. Lond. B 346, 129-150 (1994a)) will generate damped oscillations in response to a negative current pulse. As a consequence the cell has the property that it can be driven into bursting by periodic sinusoidal inputs close to the resonant frequency. The main objective of this paper is to analyse this resonant behaviour using the model of the model introduced in the previous paper. We derive analytical expressions which closely approximate the nonlinear resonance observed in the physiological model driven by a periodic sinusoidal input. This leads to the conclusion that resonance could play a role in synaptic transmission at relay nuclei in the mammalian brain.

Animals↗

PubMed1994

A model of intrinsic and driven spindling in thalamocortical neurons.

We add a slow hyperpolarization-activated inward current IH = gHmH (v-vH) to our previous model of rebound bursting (Hindmarsh & Rose Phil. Trans. R. Soc. Lond. B 346, 129-150 (1994a)) to give a four-dimensional physiological model, and a corresponding four-dimensional model of the model. The physiological model generates periodic 'bursts of bursts' or 'spindles' resembling those recorded experimentally in thalamocortical (TC) neurons. The model of the model is simplified to a two-dimensional system having a limit cycle which corresponds to the slow spindle oscillation of the physiological model. Analysis of the stability of this two-dimensional model allows us to divide the parameter space of the slope (gamma mH) and shift (theta mH) parameters of mH infinity (v) into regions in which the model generates spindles or continuous bursting. This enables us to determine the parameter values required for spindling in the physiological model and to explain the experimentally observed effects of noradrenaline. Next we examine whether a cell at a stable equilibrium point can be driven into spindling by applying a sinusoidal input at the resonant frequency. This is done by averaging the equations for the driven model of the model. Analysis of the stability of these averaged equations shows how the regions of the (theta mH, gamma mH) parameter space change when the system is driven by a sinusoidal input. This enables us to choose parameter values for a physiological model of a driven spindle. We show that if the physiological model is modified to include a voltage-dependent time constant for mH, spindles, similar to those of TC cells, can be obtained with a small Ca(2+)-activated K+ current. Finally our knowledge of the form of the bifurcation diagram and the conditions for resonance leads to a new suggestion for the roles of GABAA and GABAB inhibitory postsynaptic potentials when TC cells are driven into spindling by neurons of the nucleus reticularis thalami.

Animals↗

PubMed1994

Phytosterols are present in Pneumocystis carinii.

Although originally classified as a protozoan, Pneumocystis carinii is now considered to have fungal characteristics. Drugs typically used for the treatment of fungal infections target ergosterol. Because P. carinii is an important pathogen in AIDS and other immunocompromised patients, knowledge of the sterol content of this organism may be useful as a basis for developing new treatment strategies or for improving diagnosis. P. carinii organisms were harvested from infected rat lungs and were purified by filtration. Control preparations from uninfected animals were identically prepared. Lipids were extracted from the organisms and control preparations and were separated into neutral lipid, glycolipid, and phospholipid fractions by silicic acid chromatography. The neutral lipid fraction was further treated by alkaline hydrolysis and was analyzed by reversed-phase high-pressure liquid chromatography (HPLC), gas chromatography (GC), and GC-mass spectrometry (GC-MS). As shown by HPLC, the neutral lipid fraction from infected rats contained a minimum of six peaks, while in control preparations a single peak with a retention time identical to that of cholesterol was observed. The predominant sterol in these preparations was positively identified by GC-MS as cholesterol and constituted 80 to 90% of the total. The remaining peaks had relative retention times similar to those of phytosterols by both HPLC and GC, and the similarity of these sterols to those derived from plants and fungi was confirmed by MS. Ergosterol, however, was not present. These results provide further evidence for a close phylogenetic relationship between P. carinii and fungi and suggest that these sterols could be used as targets for drug development and for improving diagnosis.

Animals↗