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Biomedical subjects

S R Rehm

Publications and source records attributed to S R Rehm.

32 records · Page 2Linked to original sources
PubMed1985

Serum antiproteases in smokers and nonsmokers. Relationships to smoking status and pulmonary function.

In this study of 50 relatively young male smokers and an equal number of age- and race-matched male nonsmokers, smokers had a 13.3% (p = 0.007) increase in mean serum alpha 1-proteinase inhibitor (alpha 1-Pl) concentration. This increase in serum alpha 1-Pl concentration was accompanied by increases in both the serum trypsin inhibitory capacity (TIC) (9.9%, p = 0.002) and the elastase inhibitory capacity (EIC) (12.4%, p = 0.001). That cigarette smoking increases serum alpha 1-Pl concentration and total protease inhibitory capacity was further supported by a significant association of alpha 1-PI, TIC, and EIC with increased pack-years smoking history, plasma nicotine, and plasma cotinine concentrations. Pulmonary function did not correlate with serum alpha 1-PI concentration. However, higher serum TIC and EIC did correlate with tests of small airways dysfunction. Highly significant correlations (r greater than or equal to 0.6, p = 0.001) were observed between TIC (or EIC) and alpha 1-PI concentrations. The linear relationships between TIC (or EIC) and serum alpha 1-PI concentration were not significantly different in smokers and nonsmokers. Further, no significant differential effect of smoking on either the TIC or EIC could be demonstrated. A decreased apparent functional activity of alpha 1-PI (i.e., nanomoles of protease inhibited per nanomole of alpha 1-PI) was associated with its higher serum concentration, a phenomenon observed in both smokers and nonsmokers. Thus, although cigarette smoking increases serum alpha 1-PI concentration and total protease inhibitory capacity, no evidence was obtained to suggest that the functional activity of serum alpha 1-PI (against either trypsin or elastase) was directly affected by smoking.

Adult↗
PubMed1985

Effect of smoking on peripheral blood leukocytes and serum antiproteases.

Cigarette smokers have an increased risk of chronic obstructive airways disease which has been attributed to a protease-antiprotease imbalance in the lung. The neutrophil is an important source of proteases as well as of myeloperoxidase, which oxidatively inactivates alpha-1-proteinase inhibitor (alpha-1-PI). The purpose of this study is to evaluate the protease-antiprotease imbalance hypothesis by measuring changes in peripheral blood components in a group of 110 young, male, asymptomatic smokers and an equal number of age-matched non-smokers. Significant (p = 0.001), but modest impairment of pulmonary function was observed in the smokers as measured by both forced expiratory spirometry and the single breath nitrogen test. A 35% increase (p = 0.0001) in peripheral blood leukocytes in smokers was attributable to increases in neutrophils (44%), lymphocytes (31%) and monocytes (23%). This increase in leukocyte count correlated significantly (p less than or equal to 0.01) with some of the more sensitive indicators of airway obstruction (FEV1/FVC, CV/VC, CC/TLC, and delta N2/L). Myeloperoxidase activity of neutrophils isolated from peripheral blood of smokers was 13% higher than in non-smokers, while elastase activity per neutrophil was apparently unaffected by smoking. In 50 subject pairs, elevations in serum alpha-1-PI concentrations in smokers (13.7%) were comparable to similar increases in trypsin (9.9%) and elastase (12.4%) inhibitory capacities. Expressed as nanomoles protease inhibited per nanomole of alpha-1-PI, the apparent functional activity of alpha-1-PI was unaltered by smoking. However, a lower, apparent functional activity of alpha-1-PI against trypsin and elastase was observed in both smokers and non-smokers with higher serum alpha-1-PI concentrations. Thus, in a population of young smokers, changes in leukocyte count, neutrophil lysosomal enzyme activities, and functional serum antiprotease activity appear to be consistent with the establishment of a protease-antiprotease imbalance. This imbalance may predispose these smokers to obstructive lung disease.

Adult↗
PubMed1985

Increased neutrophil myeloperoxidase activity associated with cigarette smoking.

Neutrophils from 49 young male smokers contained significantly higher myeloperoxidase (MPO) activity than those from 49 age-matched, nonsmoking controls, while the elastase-like activity was not different in the two populations. MPO activity was increased in some smokers, but did not correlate significantly with the increased number of peripheral blood neutrophils, cigarette usage (present or cumulative), or the mild pulmonary dysfunction detected by forced expiratory spirometry and the single breath nitrogen test. This increased MPO activity in smokers' neutrophils may contribute to the greater risk of obstructive pulmonary disease in some smokers by an exacerbation of the protease-antiprotease imbalance in the lung. This hypothesis is supported by the prior observations that neutrophils are recruited in greater numbers into the lungs of smokers and that MPO (in the presence of H2O2 and chloride ion) oxidatively inactivates antiproteases of both the alveoli and the mucus-lined airways.

Adult↗
PubMed1984

Miliary pulmonary blastomycosis.

Five patients with proved blastomycosis had a diffuse miliary nodular pattern seen on chest radiographs. These cases are presented to emphasize that blastomycosis may be the cause of a miliary pattern in an endemic area. Documentation requires recovery of the organism from body fluids or tissue since skin and serologic testing are unreliable indicators of active disease. With prompt diagnosis and appropriate treatment, the patient may recover from this form of endogenous disseminated reinfection that otherwise may be fatal, particularly in the immunocompromised host.

Adult↗
PubMed1984

Retention of intact cells on bronchoscopy brushes after cleaning.

Reusable nylon bristle bronchoscopy brushes were evaluated to assess whether cytologically recognizable cells could be retained on the bristles after conventional cleaning techniques. Twenty brushes were used during bronchoscopy; 5 brushes were inserted directly into freshly resected neoplasms. The brushes were then scrubbed and rinsed in chlorhexidine gluconate, iodine, and alcohol, and air dried. Several days later fresh cytologic specimens were prepared from the apparently clean brushes. Eighty percent of the cytologic specimens exhibited strands of mucus, most containing well-preserved alveolar macrophages, polymorphonuclear leukocytes, and ciliated epithelial cells. Although no malignant cells were retained, it is clear that conventional cleaning techniques are inadequate for the removal of cells and acellular debris. Consideration should be given to immersing brushes in acetylcysteine or employing disposable brushes.

Bronchoscopy↗
PubMed1982

Early clearance of pneumococci from the lungs of decomplemented rats.

Pneumococcal types which exhibited varying degrees of interaction with the complement system in vitro wee aerosolized into normal and decomplemented rats, and the rate of killing of pneumococci was monitored by serial cultures of whole lung homogenates. The clearance of pneumococci from the alveoli did not correlate with the ability of the pneumococci to be opsonized by complement in vitro. Similarly, rats depleted of complement in the serum and the bronchoalveolar lavage fluid maintained their ability to rapidly inactivate aerosolized pneumococci. These results indicate that the early phase of pneumococcal killing in the alveoli does not require complement and suggest that in the nonimmune host, phagocytosis by alveolar macrophages can be achieved without complement-dependent opsonization or, alternatively, that extracellular factors rapidly inactivate inhaled pneumococci.

Animals↗
PubMed1982

Complement receptors of rat macrophages.

Some species, including rabbits, guinea pigs, and humans, have complement receptors on resident alveolar macrophages, whereas Swiss mice lack detectable receptors on these macrophages. Using complement-coated sheep erythrocytes or bacteria, we were unable to detect complement receptors (CR1, CR2, or CR3) on resident alveolar macrophages of male Sprague-Dawley rats. Nonelicited peritoneal macrophages from Sprague-Dawley rats had CR1 and CR3 receptors and were able to bind bacteria opsonized with complement. Resident alveolar macrophages of Long-Evans and Fisher rats lacked detectable complement receptors, but CR1 and CR3 receptors were detected on the alveolar macrophages of Lewis-Wistar rats. The reason for the lack of complement receptors on murine macrophages is not known, but studies of this phenomenon may prove useful in elucidating the role of macrophage complement receptors in the pulmonary inflammatory response.

Animals↗
PubMed1980

Early bacterial clearance from murine lungs. Species-dependent phagocyte response.

Two sets of phagocytic cells are available to defend the lung against inhaled bacteria. Both resident alveolar macrophages and granulocytes from the circulation have been observed in pulmonary air spaces after the deposition of bacteria; their functional roles, however, have been defined. We rendered mice selectively granulocytopenic with heterologous antiserum in order to ascertain the relative contributions of these two groups of cells in intrapulmonary bacterial killing. The clearance of Staphylococcus aureus was unimpaired in granulocytopenic animals, confirming the primary role of the alveolar macrophages in the killing of these organisms. In contrast, granulocytopenic animals cleared only 10.0+/-7.0% of an inoculum of Klebsiella pneumoniae compared with 33.0+/-4.0% clearance in normal animals (P < 0.02), and Pseudomonas aeruginosa proliferated to 513% of baseline levels in granulocytopenic animals, whereas normal mice cleared 26.8+/-10.6% of the inoculum. These findings indicate that circulating granulocytes play a major role in the clearance of the latter two organisms. This variation in cellular response to different bacterial species suggests that the defense of the lung against pathogenic bacteria is more complex than has been previously assumed.

Aerosols↗
PubMed1979

Animal model of neutropenia suitable for the study of dual-phagocyte systems.

When two sets of phagocytic cells participate simultaneously in the inflammatory process and bacterial killing, the relative contribution of each cell type is difficult to ascertain. The use of cell-specific antibody will permit selective depletion of one phagocyte population. We describe an experimental model of granulocytopenia which utilizes the immunoglobulin G fraction of an antigranulocyte serum. This material markedly depleted circulating polymorphonuclear leukocytes (PMN); within 2 h after injection of antigranulocyte globulin, PMN counts were at 19% of original levels and remained significantly depressed for 24 h. Granulocyte recruitment was also impaired, with only 5 x 10(3) PMN appearing in the lungs in response to an aerosol of Klebsiella, compared to 4.17 x 10(5) PMN in control animals (P less than 0.01). Most importantly, alveolar macrophages retained normal viability (97% versus 94% for control value, P not significant) normal phagocytic function, and normal bactericidal capacity. Antigranulocyte globulin is thus a valuable tool for the study of bacterial defense mechanisms.

Agranulocytosis↗
PubMed1978

Lung clearance of Staphylococcus aureus strains with differing protein A content: protein A effect on in vivo clearance.

We have studied the clearance from murine lungs of two strains of Staphylococcus aureus, one possessing high and the other possessing low levels of protein A.S. aureus FDA 209 and S. aureus Wood 46 were assayed for their ability to bind mouse immunoglobulin G, using an indirect radioimmunoassay. S. aureus FDA 209 binding of mouse immunoglobulin was significantly greater than that of S. aureus Wood 46 (118,909 versus 37,845 cpm). Clearance of these two strains from the lung after a 30-min aerosol inoculation period was not significantly different. The percentage of bacteria remaining in the lung was 49.2 and 55.0% at 2h, 31.8 and 33.2% at 3 h, and 25.4 and 17.2% at 4 h for protein A-rich and protein A-poor strains, respectively (P greater than 0.20 at each time). These data suggest that the previously demonstrated in vitro antiphagocytic effect of protein A may not be relevant to pulmonary clearance mechanisms.

Animals↗
PubMed1978

The effect of complement depletion on lung clearance of bacteria.

We have investigated the effect of hypocomplementemia on early pulmonary clearance of four species of bacteria. The experiments were performed in an inbred animal model to minimize immunologic variability. Complement was depleted by cobra venom factor, and activity in serum was monitored with a phagocytic assay. Bacterial specific antibodies were examined by an indirect radioimmunoassay, and animals with high levels of activity were excluded from anaysis. 4 h after aerosolization with Streptococcus pneumoniae, complement-depleted animals had cleared only 75% of the initial number of organisms, whereas saline-treated controls cleared 91% (P less than 0.01). Aerosolization with Pseudomonas aeruginosa was followed at 4 h by a twofold greater growth of organisms in the complement-depleted animals (446% of original deposition) as compared to the saline-treated controls (211% of original deposition) (P less than 0.02). Clearance of Klebsiella pneumoniae and Staphylococcus aureus were similar in complement-depleted animals and saline-treated controls. These experiments suggest that hypocomplementemia predisposes to bacterial pneumonia and may explain the high incidence of pulmonary infections in patients having impaired complement activity. Our results further indicate that varying defense mechanisms may be involved with clearing the lung of differing bacterial species.

Animals↗