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Biomedical subjects

T H Rossing

Publications and source records attributed to T H Rossing.

At least 37 records · Page 2Linked to original sources
PubMed1985

The cellular defect in alpha 1-proteinase inhibitor (alpha 1-PI) deficiency is expressed in human monocytes and in Xenopus oocytes injected with human liver mRNA.

To determine the basis for low serum concentrations of alpha 1-proteinase inhibitor (alpha 1PI) in individuals with homozygous alpha 1PI deficiency (hereafter referred to as PiZZ), biosynthesis and secretion of alpha 1PI were studied in Xenopus oocytes microinjected with hepatic mRNA and in blood monocytes (an extrahepatic site of alpha 1PI gene expression). Although both the usual alpha 1PI (hereafter referred to as PiMM) and PiZZ alpha 1PI were secreted in functionally active form, the rate of secretion of alpha 1PI was significantly and selectively decreased in Xenopus oocytes injected with PiZZ liver mRNA and in monocytes from PiZZ individuals. The apparent size of alpha 1PI in the intracellular compartment of Xenopus oocytes injected with PiZZ liver mRNA was different from the corresponding intracellular PiMM alpha 1PI in oocytes injected with PiMM liver mRNA. There were also differences in the relative ratio of native and complexed alpha 1PI secreted by monocytes from individuals with PiMM and PiZZ phenotypes.

Animals↗
PubMed1985

Expression of the alpha 1-proteinase inhibitor gene in human monocytes and macrophages.

Expression of the alpha 1-proteinase inhibitor (alpha 1PI) gene was studied in human mononuclear cells. Using RNA blot and dot hybridization, alpha 1PI mRNA was detected in human peripheral blood monocytes, bronchoalveolar and breast milk macrophages, but not in B or T lymphocytes. Using incorporation of a radiolabeled amino acid precursor, synthesis and secretion of alpha 1PI were demonstrated in human monocytes and macrophages, but not in lymphocytes. In addition, alpha 1PI was secreted in functionally active form as shown by complexing with serine proteases. Biosynthesis of alpha 1PI by mononuclear phagocytes was greatest during the first 24 hr in culture and progressively decreased over the next 10 days. The reduction in alpha 1PI biosynthesis in vitro involved a mechanism acting at the pretranslational level as alpha 1PI mRNA content also progressively declined over 10 days in culture. The ease of sampling human monocytes and macrophages now permits examination of the biochemical defect in homozygous PiZ and PiS alpha 1PI deficiencies and study of the functional significance of locally produced alpha 1PI in normal tissues and sites of injury or inflammation.

Blood Proteins↗
PubMed1985

Isolation and partial characterization of a human alveolar macrophage-derived neutrophil-activating factor.

Human alveolar macrophages (AM) were obtained from eight normal volunteers using fiberoptic bronchoscopic lavage to explore potential interrelationships among leukocytes in pulmonary defense against infection. AM placed in monolayer tissue cultures released material into culture supernatants with the capacity to enhance the bactericidal capacity of human neutrophils. Neutrophils preexposed to supernatants killed Pseudomonas aeruginosa from 70 to 90% more efficiently than control cells (P less than 0.02). AM culture supernatants contained this material by 4 h of incubation, and in vitro stimulation of AM cultures with heat-killed P. aeruginosa further increased its production. Gel filtration of AM culture supernatants with a G-50 Sephadex column allowed isolation of a 6,000-D neutrophil-activating factor (NAF) that was resistant to heat (56 degrees C, 30 min). The isoelectric point of NAF, as determined by chromatofocusing, was approximately 7.6. Enzyme digestion of NAF specimens, prepared sequentially by gel filtration and chromatofocusing, demonstrated 50-70% loss of activity after incubations with trypsin, chymotrypsin, and neuraminidase. NAF was only minimally chemotactic and eluted from Sephadex G-50 with particles of a different molecular size than those of AM-derived chemotactic factors (i.e., approximately 10,000 D and less than 500 D). Preincubation of neutrophils with NAF resulted in greater release of superoxide anion upon their subsequent stimulation by either bacterial phagocytosis or by phorbol myristate acetate, as compared with control neutrophils stimulated in a like manner. These studies indicate that human AM secrete a heat-stable, low molecular weight basic protein, with the capacity to enhance oxidative microbicidal activity of neutrophils.

Adult↗
PubMed1985

Density gradient study of bronchial mucus aspirates from healthy volunteers (smokers and nonsmokers) and from patients with tracheostomy.

Because it is difficult to obtain, little is known of bronchial mucus from the normal human airway; it has been mainly studied as sputum expectorated in chronic bronchitis with particular attention to epithelial glycoprotein. We have now applied density gradient methods to study this and other macromolecules and lipids in normal airway mucus. After lavage at bronchoscopy, mucus was aspirated from six normal volunteers, that include one light and two heavy smokers. This normal mucus has been compared with that obtained from four patients with tracheostomy because of respiratory muscle paralysis due to neurological disease. The normal aspirates contained small threads of mucus, the tracheostomy aspirates viscous blobs of jelly, a difference in physical appearance reflected in macromolecular yields, 0.3-1 mg/ml and 6-24 mg/ml respectively. On analytical ultracentrifugation normal mucus showed no discernible material in the buoyant density region typical of epithelial glycoprotein (1.5 g/ml): Virtually all the material migrated to the miniscus and was predominantly lipids and proteins. A trace amount of material recovered from a higher density region (greater than or equal to 1.6 g/ml) was found to contain both glycoprotein and proteoglycan. Aspirates from the heavy smokers contained appreciable amounts of material with typical buoyant density (approximately 1.5 g/ml) but still with features of proteoglycan. In contrast in tracheostomy aspirates epithelial glycoprotein of typical buoyant density and chemical composition accounted for up to 25% of nondialyzable material. We conclude that under normal conditions typical epithelial glycoprotein is virtually absent from airway mucus and that the glycoconjugate present has features of glycoprotein and proteoglycan.

Adult↗
PubMed1984

Physiological bases for new approaches to mechanical ventilation.

High frequency ventilatory (HFV) techniques offer potential advantages over conventional forms of mechanical ventilation in patients with diverse forms of respiratory insufficiency. In some respects, HFV challenges conventional physiologic concepts regarding gas transport in the lung. We review hypotheses regarding the mechanism of gas transport and provide a brief perspective on current clinical applications of these techniques.

Humans↗
PubMed1984

Influence of the endotracheal tube on CO2 transport during high-frequency ventilation.

Low-volume, high-frequency ventilation (HFV) delivered via an endotracheal tube can maintain eucapnia in both humans and animals. Because recent animal studies have suggested that a substantial fraction of the resistance to gas transport during HFV can be attributed to the presence of the endotracheal tube, we evaluated the importance of the endotracheal tube on carbon dioxide elimination (VCO2) during HFV in humans. We compared the effectiveness of delivering the fresh gas bias flow at the proximal and the distal end of an endotracheal tube. For each bias flow position, we ventilated patients using tidal volumes of 60 ml or less and frequencies from 0.5 to 12 Hz. In each case, VCO2 was approximately 50% greater when the fresh gas was introduced at the carinal end of the endotracheal tube. Thus, the endotracheal tube contributed about one third of the resistance to HFV-induced CO2 transport in these patients. These results indicate that the position of the fresh gas source strongly influences the effectiveness of HFV.

Adult↗
PubMed1984

Surface membrane heterogeneity among human mononuclear phagocytes.

Considerable information has been accumulated about the functional and metabolic differences that exist among human mononuclear phagocytes isolated from different anatomic sites. This heterogeneity may reflect the influence of environmental factors that stimulate circulating monocytes to differentiate in a distinctive manner, or may suggest the existence of predetermined subsets of macrophage precursors. The present study was designed to evaluate macrophage diversity at the membrane level by defining the expression of antigenic determinants on the surface of these cells. The expression of two new membrane differentiation antigens, BMM1 and PAM1, and of Mo1 and Mo2 were evaluated on blood monocytes, macrophages derived from cultured monocytes, breast milk macrophages (BMM), pulmonary alveolar macrophages (PAM), and peritoneal macrophages. Anti-BMM1 is a mouse IgG2a monoclonal antibody obtained by immunization with breast milk cells that recognizes an antigen expressed only on BMM but not on blood monocytes (or any other circulating cells), PAM, and peritoneal macrophages. BMM1 expression is also seen on HL60 promyelocytes induced toward macrophage differentiation by lymphokines but not by phorbol diester. Anti-PAM1, an IgG1 monoclonal antibody raised by immunization with PAM, reacts with an antigen found only on PAM. Blood monocytes, BMM, and peritoneal macrophages all share the previously described differentiation antigens, Mo1 and Mo2 (as well as Ia), whereas these markers are not found on PAM. BMM1 is associated with a two subunit surface protein of 46 and 40 Kd, and PAM1 resides on a 200 Kd polypeptide. The appearance of new antigens during differentiation (BMM1 on milk macrophages and PAM1 on PAM) and the disappearance of antigens more common to the macrophage lineage (absence of Mo1 and Mo2 on alveolar macrophages) indicate a significant heterogeneity at the membrane level among phagocytes obtained from different anatomic sites (but arising from a common myeloid precursor). The functional relevance of these structures selectively expressed by BMM and PAM is the object of further investigation.

Antibodies, Monoclonal↗
PubMed1984

Lung inflation during high-frequency ventilation.

We investigated the relationship between mean airway pressure and lung volume during low-tidal-volume, high-frequency ventilation (HFV). Eight patients requiring mechanical ventilatory support for treatment of respiratory insufficiency were studied by imposing rapid (60 to 600 breaths/min) oscillations with low tidal volumes (50 to 150 ml) at a constant mean airway pressure of 5 cm H2O. Despite this constant mean airway pressure, lung volume increased substantially during the oscillation period in 7 of 8 subjects, as indicated both by an increase in thoracoabdominal dimensions and by an increase in respiratory system relaxation pressures after the oscillations were stopped. For each patient in whom these changes occurred, the degree of lung inflation rose progressively with increases in either frequency or tidal volume. Given this dissociation between lung volume and mean airway pressure, some index of lung volume or alveolar pressure should be monitored to minimize the likelihood of adverse effects during HFV.

Adult↗
PubMed1983

Effect of outpatient treatment of asthma with beta agonists on the response to sympathomimetics in an emergency room.

It has been suggested that tolerance to the bronchodilating effects of sympathomimetics may develop in asthmatic patients after long-term use of these agents. In an emergency room setting, the effects of inhaled and injected sympathomimetic therapy in 58 patients who had pretreated themselves with beta agonists were compared with the results observed in 38 patients who had not used such drugs. The two groups had similar degrees of obstruction on presentation and were also well-matched with respect to the clinical features of their illness. Both populations showed equal responses to treatment; no significant differences were found in either the amount of bronchodilation or the incidence of adverse effects in those who had or had not taken sympathomimetics as outpatients. These findings indicate that drug resistance does not account for outpatient treatment failures with sympathomimetics and that beta agonists can be usefully employed in the treatment of acute asthma, irrespective of a patient's medication history.

Adolescent↗
PubMed1983

Glucocorticoids in acute asthma. A critical controlled trial.

In order to determine objectively the efficacy of corticosteroids in relieving severe acute episodes of asthma, we administered infusions of hydrocortisone or placebo in a random, double-blind manner to 20 asthmatic subjects after they had been documented to be refractory to eight hours of conventional therapy. Eleven subjects received hydrocortisone (2 mg/kg bolus, then 0.5 mg/kg per hour for 24 hours) and nine received saline. All were given identical bronchodilator treatment during the study period, and all had multiple aspects of lung function serially recorded along with plasma cortisol levels. Although subjects in both groups had severe obstruction of similar magnitude at the beginning of treatment (one-second forced expiratory volume [FEV1] in placebo-treated group = 32 +/- 3 [SEM] percent of predicted, and 25 +/- 3 percent of predicted in steroid-treated group, p = NS), at the end of 24 hours, the subjects given corticosteroids had significantly greater resolution of airway obstruction (FEV1 in steroid-treated group increased 118 +/- 25 percent from control value, versus 35 +/- 22 percent with placebo). In five of nine subjects treated with placebo, pulmonary mechanics either were unchanged or deteriorated during the period of observation. There was no effect of the glucocorticoids on arterial blood gases, and no significant correlation could be found between plasma cortisol levels and the improvement in pulmonary mechanics and clinical status. These results provide objective documentation of the time course over which administration of parenteral corticosteroids speeds the recovery of asthmatic patients who are unresponsive to standard therapy.

Adolescent↗
PubMed1983

Complement biosynthesis by human bronchoalveolar macrophages.

Complement production by bronchoalveolar macrophages recovered from 8 normal volunteers and 15 patients with a variety of lung diseases was measured functionally and immunochemically. While macrophages from all eight normals demonstrated the capacity to secrete hemolytically active C2 and factor B within 48 hr of culture at consistent rates, bronchoalveolar macrophages from patients secreted C2 and factor B in widely differing amounts, and in some cases, not at all. No functional, secreted C3 was detected from normal macrophage monolayers, although apparently native C3 protein was synthesized and secreted. In contrast, functional C3 was produced by macrophage monolayers from 3 of 15 patients. These findings suggest that complement production by the normal human bronchoalveolar macrophage differs from its progenitor cell, the blood monocyte, and that complement production by bronchoalveolar macrophages may be altered in different pulmonary diseases.

Adult↗
PubMed1983

Relationship between bronchial responsiveness to hyperventilation with cold and methacholine in asthma.

Twenty-seven subjects with asthma and normal baseline lung function were challenged with aerosols of methacholine (M) and by isocapnic hyperventilation with cold air (HV). Stimulus-effect relationships were determined for each provocational technique on separate days and were expressed as the dose required to produce a 20% fall in forced expired volume in 1 sec (FEV1) obtained by linear interpolation from log stimulus vs. response curves (PD20). Each stimulus was applied with a sufficient intensity to produce a 20% or greater fall in FEV1 in each subject. The PD20 for M correlated significantly with the PD20 for HV (p less than 0.001) when the latter was expressed in liters per minute. The correlation between cumulative M PD20 and HV PD20 expressed as a percent of maximal voluntary ventilation was significant but less strong. We conclude that the airway response to HV reflects nonspecific bronchial hyperresponsiveness and that the dose of HV is best determined as the absolute level of ventilation.

Adolescent↗
PubMed1983

The effect of human alveolar macrophages on the bactericidal capacity of neutrophils.

Human alveolar macrophages (AMs) were obtained by bronchoscopy from 11 healthy adult subjects and placed into tissue culture for 24 hr. Brief preexposure (15 min) of human neutrophils to AM culture supernatants led to a greater than twofold increase in neutrophil killing of a serum-resistant strain of Pseudomonas aeruginosa (P less than 0.02). No increase in phagocytosis of 35S-labeled Pseudomonas could be detected for neutrophils preexposed to AM supernatants. However, upon exposure to bacteria, neutrophils preincubated with AM supernatants generated significantly more (P less than 0.05) superoxide anion than controls. This suggested that AM supernatants enhanced neutrophil oxidative bactericidal capacity. The material in AM supernatants which enhanced neutrophilic killing of Pseudomonas was less than 10,000 daltons in mass and heat-stable (56 C for 30 min). Release of this material was partially inhibitable by exposure of AMs to cycloheximide in tissue cultures. These data suggest that an AM-mediated amplification of neutrophil bactericidal capacity might be important in the defense of the human lung.

Adult↗
PubMed1983

Effect of intermittent mandatory ventilation on respiratory drive and timing.

Seven patients receiving chronic ventilatory support were studied to better define the effects of intermittent mandatory ventilation (IMV) on the control and timing of spontaneous breathing between mandatory breaths. Each of these patients could sustain adequate spontaneous ventilation, as reflected by stable end-tidal carbon dioxide concentration (FETCO2), and arterial oxygen saturation (SO2) during periods of unassisted ventilation of sufficient duration to allow study. Inspiratory time (TI), respiratory cycle duration (Ttot), tidal volume (VT), and tracheal occlusion pressure (P0.1) were measured as IMV rate was progressively reduced. Respiratory timing was unaltered by decreasing IMV frequency; however, VT increased progressively. The P0.1 and mean inspiratory flow rate (VT/TI) also increased with each decrease in IMV rate, whereas FETCO2 and arterial SO2 remained constant. Thus, in these stable but ventilator-dependent patients, IMV did not alter respiratory timing or chemical stimuli, but it did alter respiratory drive as measured by VT/TI and P0.1.

Adult↗
PubMed1982

Emergency room of treatment of asthma. Relationships among therapeutic combinations, severity of obstruction and time course of response.

In an effort to determine the optimal emergency therapy for acute episodes of asthma, we randomly, assigned 102 acute ill patients to 60 minutes of treatment with inhaled isoproterenol alone, isoproterenol plus intravenous aminophylline or isoproterenol plus a single oral dose of an elixir of theophylline. Patients requiring treatment beyond this time were given an injectable sympathomimetic agent in addition. The combination of isoproterenol and a methylxanthine was not found to be better than isoproterenol alone, and the route of administration of methylxanthine was not an important determinant of either the serum theophylline level or the therapeutic response. A major variable that influenced the duration of therapy needed to produce a remission was the severity of the obstruction at presentation. Persons whose initial 1-second forced expiratory volumes were less than 30 percent of predicted and who did not improve 35 percent or more to at least 40 percent of predicted at the end of 60 minutes of intense treatment were those who ultimately required prolonged emergency room therapy and/or hospital admission for control of their symptoms. Thus, simple objective assessment of the degree of impairment at presentation coupled with the response to initial treatment will serve to identify early a high-risk group of asthmatic patients in whom the usual emergency room therapeutic modalities will often prove ineffective.

Adolescent↗
PubMed1982

Prevalence of abnormal thyroid function test results in patients with acute medical illnesses.

We measured serum total and free thyroxine (T4) and triiodothyronine (T3) concentrations, free T4 and T3 indexes, thyroid-stimulating hormone (TSH), thyroxine-binding globulin (TBG) and thyroxine-binding prealbumin (TBPA) concentrations in 98 patients hospitalized for acute medical illnesses. The free thyroxine index (FT4I) or TSH level was abnormal in 16 percent, but only 3 percent had thyroid disease. Serum fre T4 measurements by equilibrium dialysis were abnormal in 25 percent, but no additional patients who initially had abnormal concentrations of serum free T4 were subsequently proved to have thyroid disease. Patients with supranormal serum free T4 concentrations (21 percent) ahd higher serum T4, lower serum T3, and higher serum reverse T3 (rT3) concentrations than other patients, but the measured changes in serum T4, TBG and TBPA levels could only partly account for the magnitude of the free T4 elevation. In these acutely ill patients, an accurate diagnosis of thyroid disease could be achieved by determination of FT4I and TSH level and a history of medication usage. We conclude that other tests are rarely necessary for this purpose in a patient population such as this.

Acute Disease↗
PubMed1982

Effects of inhaled sympathomimetics on obstructive response to respiratory heat loss.

To investigate the influence of inhaled sympathomimetics on the obstructive response to airway cooling, we had six asymptomatic atopic asthmatics perform eucapnic hyperventilation with frigid air at various levels of ventilation after pretreatment with aerosols of metaproterenol or placebo in a random blind fashion. In control experiments, eucapnic hyperventilation produced a progressive decrease in 1-s forced expiratory volume in a stimulus-response fashion as the level of ventilation rose in successive challenges. Metaproterenol did not produce an all-or-none blockade, but rather a parallel shift in the stimulus-response curve so that its protective effects could be overcome by increasing the stimulus. There was no effect on respiratory heat loss. These results explain, in a quantitative fashion, why a treatment schedule that permits a person with asthma to perform a given exercise task without difficulty becomes ineffective as the thermal burden or severity of the task increases.

Adult↗