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Biomedical subjects

R M Rose

Publications and source records attributed to R M Rose.

At least 73 records · Page 4Linked to original sources

The assembly of ionic currents in a thalamic neuron. II. The stability and state diagrams.

In the previous model of a thalamic neuron (R.M. Rose & J.L. Hindmarsh, Proc. R. Soc. Lond. B237, 267-288 (1989], which we referred to as the z-model, the burst response was terminated by the slow activation of a subthreshold outward current. In this paper we show that similar results can be obtained if the burst response is terminated by slow inactivation of the subthreshold inward current, Isa. We illustrate the use of this new model, which we refer to as the ha-model, by using it to explain the response of a thalamic neuron to a double ramp current. The main aim of the paper is to show how the stability and state diagrams introduced previously can be used to explain various types of firing pattern of thalamic and other neurons. We show that increasing the threshold for the fast action potentials leads to low threshold spikes of increased amplitude. Also, addition of a second subthreshold inward current adds a new stability region, which enables us to explain the origin of plateau potentials. In addition, various types of subthreshold oscillation are produced by relocating a previously stable equilibrium point in an unstable region. Finally, we predict a sequence of responses to current steps from different levels of background current that extends the burst, rest, tonic sequence of thalamic neurons. The stability and state diagrams therefore provide us with a useful way of explaining further properties of thalamic neurons and appear to have further applications to other mammalian neurons.

Action Potentials↗

The assembly of ionic currents in a thalamic neuron. III. The seven-dimensional model.

We replace our earlier three-dimensional ha-model of a thalamic neuron (Rose & Hindmarsh, Proc. R. Soc. Lond. B 237, 289-312 (1989b)) by a seven-dimensional ha-model. The stability and state diagrams for this seven-dimensional model are shown to be similar to those of the three-dimensional system with which it is compared. Two examples that illustrate how the seven-dimensional model can be related to experimental recordings are then discussed in detail. In each case we show the state and stability diagrams and the time courses of the different ionic currents during the burst response. We discuss how the various components of the state diagram could be determined experimentally. These experiments are illustrated by using our model to simulate the results of actual experiments. Finally the state and stability diagrams are transferred to a current-voltage diagram. This shows the advantage of the state diagram compared with the current-voltage diagram for representing the dynamics of the firing of a thalamic neuron.

Animals↗

Elastase inhibitor. Characterization of the human elastase inhibitor molecule associated with monocytes, macrophages, and neutrophils.

A fast-acting inhibitor of serine elastase has been detected at high levels in human neutrophils, fresh monocytes, matured monocytes, and macrophages. The elastase inhibitor was isolated from large scale cultures of the monocyte-like cell line U937 by DNase chromatography, disulfide exchange, Phenyl-Sepharose, Red A-agarose, and DEAE HPLC chromatography with an average yield of 480 micrograms from 1.8 x 10(10) cells. The isolated polypeptide was verified as elastase inhibitor by its ability to (a) form a covalent complex with elastase; and (b) inhibit the elastinolytic activity of elastase. The purified elastase inhibitor molecule is unique, i.e., physiochemical and/or functional properties distinguish it from all other serine proteinase inhibitors. Treatment with iodoacetamide abrogates the ability of the molecule to form a complex with elastase, thereby providing evidence for the presence of an essential cysteine residue. Based on functional criteria, this elastase inhibitor has been grouped with the proteinase inhibitors of the serpin superfamily. The purified elastase inhibitor is a single polypeptide of Mr approximately 42,000. The NH2 terminus appears to be blocked. Compositional analyses indicates five cysteine residues per molecule of approximately 360 amino acid residues. Negligible levels of carbohydrate were detected on gas-liquid chromatography. This finding and the insensitivity of the molecule to peptide N-glycosidase F treatment strongly indicate that the elastase inhibitor is a nonglycosylated protein.

Amidohydrolases↗

Type A, amicability and injury: a prospective study of air traffic controllers.

Recent research has suggested that only a subset of Type A's may be at higher risk for negative health outcomes. The present prospective study of 416 air traffic controllers attempted to determine if a sub-group of Type A's who were disliked by their co-workers had significantly higher risk of injury than liked A's and all Type B's over a 27-month period. Liked B's were not different in terms of injury incidence from their not liked B counterparts (mean annualised rates of injury = 1.9 and 2.1 respectively); not liked Type A's had the highest rates of injuries of any group (8.5) including liked Type A's (3.8). Some psychological instruments were useful in discriminating the Type A not liked group from their liked counterparts and from the Type B's. These discriminating variables were used as covariates to determine if the relationship between being classified a not liked Type A and elevated injury incidence remained. Multiple regression analysis showed that distress from life events and being a not liked Type A remained significantly correlated with later injury (standardised coefficients 0.16 and 0.25 respectively).

Adult↗

Blood platelet uptake of serotonin in episodic aggression.

Blood platelet uptake of 3H-serotonin (5HT uptake), a potential marker of serotonergic function, was determined in male outpatients with episodic aggression (n = 15) and in age- and sex-matched nonaggressive controls (n = 15). Correlations with rating scales of "impulsivity" (Barratt Impulsivity Scale, 10th revision) and "anger" (Spielberger Anger Expression Scale) were performed. Mean 5HT uptake was 18% lower in patients with episodic aggression. A significant negative correlation between % difference in platelet 5HT uptake and impulsivity score was observed, but the correlation between 5HT uptake and anger was not significant. These results support the hypothesis of disturbed serotonergic function in aggression and suggest that the primary relationship is in the "control" of aggression. The blood platelet may be useful in identifying impulsive subtypes.

Adolescent↗

Altered susceptibility to viral respiratory infection during short-term exposure to nitrogen dioxide.

The studies reported here focus on the relation of nitrogen dioxide exposure to susceptibility to viral respiratory infection in a murine model of pneumonia, created by intratracheal inoculation of an endogenous murine pathogen, mouse cytomegalovirus. The purpose of this work is to clarify the potential role of nitrogen dioxide exposure in the pathogenesis of viral infection of the lower respiratory tract. Previous human epidemiologic studies have presented conflicting information about the relationship of nitrogen dioxide to acute, self-limited episodes of respiratory illness, which are characteristic of viral respiratory infection. Some studies have found an association between exposure to elevated ambient levels of nitrogen dioxide and increased occurrence of acute respiratory illness. In one study this association was found to be strongest in children in the first two years of life. However, other epidemiologic studies have failed to observe this relation. To determine if there is scientific evidence for the possible relation of nitrogen dioxide exposure to human respiratory infection, our studies were performed to assess the impact of nitrogen dioxide on respiratory tract susceptibility to initial, or primary, infection, as well as to recurrent infection, or reinfection, with the identical virus. The latter mechanism of viral respiratory infection is of particular interest, since reinfection is a common method for the development of infection of the lower respiratory tract during early childhood. Outbred CD-1 mice were exposed to either air or nitrogen dioxide for six hours a day on two consecutive days prior to inoculation with murine cytomegalovirus, and then were reexposed to the same level of nitrogen dioxide for six hours a day on four consecutive days, beginning the day after viral inoculation. Susceptibility to primary infection was determined by inoculating animals with an amount of virus (10(2) plaque-forming units) that is too small to produce viral infection in the lungs of normal animals. Mice exposed to 5 parts per million (ppm) nitrogen dioxide routinely developed viral replication in the lung and histologic evidence of pneumonitis after inoculation with this amount of virus, whereas air-exposed animals did not. Most importantly, animals exposed to 5 ppm nitrogen dioxide could be infected with a viral inoculum that was 100-fold smaller than that required to consistently produce viral infection in air-exposed mice. Enhanced susceptibility to infection was found after exposure to 5 ppm nitrogen dioxide, but was not observed with exposure to 2.5 or 1 ppm nitrogen dioxide.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Diminished perception of inspiratory-resistive loads in insulin-dependent diabetics.

Diabetes mellitus is known to be associated with impaired perception of sensory input from organs such as the heart. To determine whether diabetics have a diminished ability to perceive respiratory sensations, we compared the abilities of patients with insulin-dependent diabetes (n = 17) and nondiabetic controls (n = 13) to detect inspiratory-resistive loads. The subjects were evaluated as they breathed through a tube-manifold apparatus with resistance that was varied randomly. They indicated whenever they perceived increased resistance to inspiration. The threshold for detecting added inspiratory resistance was expressed as a fraction of the background resistance of the subject plus that of the apparatus. This fraction, known as the Weber fraction, was 0.53 +/- 0.19 (mean +/- SD) in diabetics with neuropathy, 0.38 +/- 0.24 in diabetics without neuropathy, and 0.29 +/- 0.15 in nondiabetic controls. The differences in the mean value of the Weber fraction among the three groups were significantly different from zero (F = 4.57, P less than 0.025). There was not a significant correlation between the Weber fraction and age, degree of autonomic dysfunction, pulmonary function, cigarette smoking, or degree of diabetic control. The Weber fraction correlated with the duration of diabetes (r = 0.57, P less than 0.02). We conclude that patients with insulin-dependent diabetes may have an impaired ability to perceive inspiratory-resistive loads. This increased threshold for the perception of respiratory sensations may lead to delayed recognition of pulmonary disease in diabetics.

Adult↗

Cytokine activation of antibacterial activity in human pulmonary macrophages: comparison of recombinant interferon-gamma and granulocyte-macrophage colony-stimulating factor.

We examined the ability of two recombinant human cytokines, granulocyte-macrophage colony-stimulating factor (rHu-GM-CSF) and interferon-gamma (rHu-IFN-gamma) to activate antibacterial mechanisms in human pulmonary macrophages (PM) and peripheral blood monocytes (PBM). Growth of Legionella pneumophila (LP) was assessed in PM or PBM which had been exposed to either rHu-IFN-gamma (500-1000 u/ml) or rHu-GM-CSF (1 to 10,000 u/ml). In both PM and PBM exposed to 500 u/ml rHu-IFN-gamma, growth of LP was reduced compared to cells exposed to media alone. By comparison, exposure of these cell types to rHu-GM-CSF had no detectable effect on bacterial replication. In order to investigate potential mechanisms accounting for this observation, the effect of these cytokines on the hydrogen peroxide (H2O2)-releasing capacity of cells was studied. Exposure of PM and PBM to rHu-IFN-gamma (500 to 1000 u/ml) resulted in increased production of H2O2 triggered by phorbol myristate acetate; when subjected to the same experimental conditions, rHu-GM-CSF-exposed cells exhibited no increase in H2O2 production. To further clarify the role of rHu-IFN-gamma-induced augmentation of oxidative metabolism on cellular inhibition of bacterial growth, an amount of catalase capable of completely neutralizing extracellular H2O2 was added to cells before and during infection. This did not abrogate the antibacterial activity of rHu-IFN-gamma. These studies demonstrate that rHu-IFN-gamma but not rHu-GM-CSF is capable of augmenting the capacity of PM and PBM to restrict LP growth. These data suggest that the antibacterial activity of rHu-IFN-gamma in this system may involve oxidative as well as nonoxidative mechanisms.

Bacteria↗

Global mechanical consequences of reduced cement/bone coupling rigidity in proximal femoral arthroplasty: a three-dimensional finite element analysis.

Component loosening in total hip arthroplasty is often accompanied by substantial bony remodelling, associated initially with reduced stiffness of the cancellous bone bordering the cement, and eventually with the formation and proliferation of a compliant fibrous membrane at the bone/cement interface. An anatomically based three-dimensional finite element model has been developed to explore the salient stress changes occurring with progressive degradation of the stiffness of the cancellous bone in a thin zone bordering the cement. This border zone, modelled as a distinct linearly elastic and isotropic material layer, assumed a geometry and a range of mechanical properties inferred from eventual membrane thickness apparent in recent animal studies of component loosening. The major variables considered were: stiffness (elastic modulus) and compressibility (Poisson ratio) of the border zone, stiffness changes in the outlying cancellous bone, resultant hip contact force, and trochanteric muscle loadings. The results for the limiting case of a non-degraded border zone compared reasonably with previous studies of femoral reconstructions having rigid bone-to-cement attachment. Progressive decay of border zone stiffness produced complex changes in load transmission. Foremost among these were a generalized increase in stress levels (especially of transverse-plane tension) in the proximo-lateral cancellous bone, and a corresponding generalized decrease in stress levels in the proximo-medial cancellous bone. There were also large bending moment increases in the prosthesis and its cement mantle, especially at mid-stem. At almost all sites, the critical stress levels were those developed for peak stance-phase loading, rather than for the lower loads (and different resultant contact force directions) occurring elsewhere in the gait cycle. The elevated proximo-lateral cancellous bone stresses occurring with eventual membrane development, consistent with localized bony hypertrophy seen in recent animal studies, may be a response to hoop stresses occurring during pistoning of the tapered cement mantle.

Bone Cements↗

Localization of distinct monoamine oxidase A and monoamine oxidase B cell populations in human brainstem.

Monoclonal antibodies, specific for either monoamine oxidases A or B, were used to determine the localization of monoamine oxidase in the human brain. Two distinct populations of neurons were detected by immunocytochemical staining. Neurons in regions rich in catecholamines were positive for monoamine oxidase A, including the nucleus locus coeruleus, the nucleus subcoeruleus and the medullary reticular formation. In these regions, monoamine oxidase A could be co-localized with the synthetic enzyme, dopamine-beta-hydroxylase. Neurons in the substantia nigra and the periventricular region of the hypothalamus, areas rich in dopamine neurons, stained for monoamine oxidase A but with much less frequency and intensity. The major accumulation of monoamine oxidase B-positive neurons was observed in the same regions in which monoamine oxidase B is found to co-localize with serotonin in monkey tissues, including the nucleus raphe dorsalis and the nucleus centralis superior. In addition, both monoamine oxidase A and B were localized in distinct populations of neurons in the lateral and tuberal regions of the hypothalamus, a region shown recently to contain histamine neurons in rats. Some glial cells were stained throughout the brain for monoamine oxidase A or B suggesting that glia are capable of either expression or uptake of these proteins.

Antibodies, Monoclonal↗

A scale for the estimation of sleep problems in clinical research.

Problems in sleeping are widely prevalent in modern society and are often one of the presenting complaints of patients consulting physicians. In addition, there is scattered epidemiologic evidence and considerable clinical support that disturbed or inadequate sleep may be a risk factor for clinical emergence of cardiovascular disease and for total mortality. The role of sleep problems both as a precursor and as a sequela of disease states could be better delineated in large groups by the availability of a brief, reliable and standardized scale for sleep disturbance. Such a scale could also be used to evaluate the impact of different therapies upon sleep problems. This paper presents data from two study populations responding to three and four item self-report scales. From 9 to 12% of air traffic controllers reported various sleep problems to have occurred on half or more of the days during the prior month, whereas 12-22% of patients 6 months after cardiac surgery reported such frequent sleep problems. Utilizing data from the 6 and 12 month follow-ups, test-retest reliability of the three-item scale in cardiac surgery patients was found to be 0.59. Internal consistency coefficients for the three and four-item scales were 0.63 and 0.79 respectively.

Adult↗

The pathophysiology of enhanced susceptibility to murine cytomegalovirus respiratory infection during short-term exposure to 5 ppm nitrogen dioxide.

To determine whether exposure to nitrogen dioxide (NO2) affects respiratory tract susceptibility to viral infection, CD-1 mice were inoculated intratracheally with murine cytomegalovirus (MCMV) during exposure to varying concentrations of NO2. Exposure lasted for 6 h per day; it began 2 consecutive days prior to instillation of MCMV and continued for 4 days after virus inoculation. Exposure to 5 ppm NO2 resulted in MCMV proliferation and a mild bronchopneumonia in some animals inoculated with 10(2) plaque-forming units of virus. Importantly, this inoculum was too low to produce either viral replication or histologic abnormalities in the lungs of air-exposed animals. We also found that the amount of virus required to infect animals exposed to 5 ppm of NO2 was 100-fold lower than that needed to consistently produce infection in air-exposed animals. Animals exposed to 5 ppm NO2 also exhibited depressed phagocytosis of colloidal Au198 in vivo as well as diminished macrophage destruction of instilled MCMV compared to air-exposed animals. These results demonstrate that exposure to 5 ppm NO2, although not associated with evidence of overt lung injury per se, is nevertheless capable of predisposing the lower respiratory tract to viral infection.

Animals↗

Abnormal airway function in individuals with the acquired immunodeficiency syndrome.

Pulmonary function test results of individuals with the acquired immunodeficiency syndrome (AIDS) were analyzed to determine the prevalence of abnormally low forced expiratory flow rates and bronchial hyperreactivity. Of 99 individuals with AIDS, a total of 44 (44 percent) had either low forced expiratory flow rates or a significant response to inhaled bronchodilator. Thirty-one (31 percent) individuals exhibited significant improvement in airflow rates after bronchodilator inhalation, while 33 (33 percent) had low flow rates. Twenty (20 percent) individuals had both low flow rates and a significant response to bronchodilator. In 83 percent of symptomatic individuals treated with bronchodilators there was clinical improvement. Thus, we conclude that abnormally low forced expiratory flow rate with or without bronchial hyperreactivity is a common and treatable complication of AIDS.

Acquired Immunodeficiency Syndrome↗

Pulmonary infiltrates and hypoxemia in patients with the acquired immunodeficiency syndrome re-exposed to trimethoprim-sulfamethoxazole.

Fever, hypotension, pulmonary infiltrates, and hypoxemia developed upon re-exposure to trimethoprim-sulfamethoxazole in 2 patients with the Acquired Immunodeficiency Syndrome. This reaction can mimic sepsis or the clinical worsening of underlying pulmonary opportunistic infection. The literature concerning adverse pulmonary effects of trimethoprim-sulfamethoxazole is reviewed.

Acquired Immunodeficiency Syndrome↗

The incidence and implications of chest radiographic abnormalities following orthotopic liver transplantation.

A study of 23 patients undergoing orthotopic liver transplantation revealed that 80% of patients developed a clinically significant chest radiographic abnormality. Localized chest radiographic abnormalities generally occurred within the initial postoperative weeks and appeared to be related to the surgical procedure. Diffusely abnormal chest radiographs were most often associated with an infectious pneumonitis and rarely occurred prior to the third postoperative week. Two patients developed unusual pulmonary calcifications demonstrable by computed tomography and radionuclide bone scan.

Calcinosis↗