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Biomedical subjects

D M Musher

Publications and source records attributed to D M Musher.

At least 127 records · Page 7Linked to original sources
PubMed1987

Phagocytosis and killing of Haemophilus influenzae by alveolar macrophages: no difference between smokers and non-smokers.

The susceptibility of smokers to pneumonia caused by Haemophilus influenzae may result from impairment of phagocytic or bactericidal function of pulmonary alveolar macrophages (PAM). We compared ingestion and killing of non-typable H. influenzae and H. influenzae type B by alveolar macrophages from asymptomatic smokers and non-smokers. Three times as many cells were recovered from bronchoalveolar lavage of smokers. Non-typable H. influenzae (NTHI) were phagocytosed and killed readily by PAM from both groups of subjects, while H. influenzae type B were resistant to phagocytosis. No difference in uptake of bacteria was detected between PAM of smokers and non-smokers. PAM from smokers had a slightly greater bactericidal activity than PAM from non-smokers. These results suggest that other host factors, such as impaired tracheobronchial clearance or the presence of conditions that favor bacterial growth rather than damage to alveolar macrophages, are responsible for the susceptibility of smokers to Haemophilus infections.

Adult↗
PubMed1986

Characterization of the antigenic determinants and host components in immune complexes from patients with secondary syphilis.

Sera from patients with secondary syphilis were evaluated for abnormal levels of circulating immune complexes (IC), immunoglobulins (Ig), and complement components. Clq-solid-phase assays (Clq-SPA) that made use of monoclonal and polyclonal antibodies directed against IgG subclasses indicated that human IC were composed primarily of IgG3 and IgG1; these findings appeared consistent with subclass profile responses of electrophoretically transferred blots (Western blots) of Treponema pallidum reacted with syphilitic sera. Complexes were isolated from reactive sera by polyethylene glycol precipitation followed by either anti-Clq column chromatography or protein A-Sepharose chromatography. Although qualitative and quantitative differences were noted, all purified materials contained a treponemal polypeptide antigen with a m.w. of approximately 87,000. Subsequent analysis of this polypeptide, which was also present in purified IC from rabbits with experimental syphilis, suggests that it may represent the fibronectin receptor of the organism. The 76,000 and 66,000 materials, earlier identified in purified rabbit IC, appeared to represent C-terminal degradation products of fibronectin presumably of host origin, rather than treponemal antigens. Although fibronectin binds avidly to Clq and could represent a co-precipitable contaminant throughout the isolation procedure, anti-fibronectin antibodies in the sera of patients detectable by radioimmunoassay and the present of antibodies to 76,000 and 66,000 dalton fibronectin fragments in the globulin fractions of disassociated complexes argues against such a conclusion.

Adolescent↗
PubMed1986

Natural and vaccine-related immunity to Streptococcus pneumoniae.

To investigate the protective effects of pneumococcal vaccine, we assayed serum from healthy adults and from elderly bronchitics for antibody and opsonic activity against nine serotypes of S. pneumoniae. Before vaccination, there was no relation between opsonization and the level of antibody measured by RIA. Some serotypes were well opsonized in the absence of detectable antibody to capsular polysaccharide; others were not, despite modest levels of antibody. These in vitro studies did not support the concept that a certain level of antibody (e.g., greater than or equal to 250 ng of antibody nitrogen/ml) was specifically associated with the capacity to opsonize pneumococci. Nearly all postvaccination sera had increased antibody and opsonic activity against all serotypes, but the lack of correlation in any individual serum persisted. RIA showed that pre- and postvaccination levels of antibody in elderly adults with chronic lung disease were similar to those of younger adults. In elderly bronchitics, opsonizing activity for six of the nine serotypes was lower after vaccination, a result of suggesting a possible explanation for the failure of pneumococcal vaccine to be fully protective in these subjects. Elderly subjects had higher levels of antibody to phosphocholine, but when isolated, this antibody did not opsonize any of the vaccine strains of pneumococci. These results suggest that alternative strategies are needed to maximize the protective effect of pneumococcal vaccine in the population at greatest risk.

Adult↗
PubMed1986

Emergence of bactericidal and opsonizing antibody to Vibrio vulnificus following bacterial infection.

Virulent isolates of Vibrio vulnificus resist the bactericidal and opsonizing effects of normal human serum, in contrast to environmental isolates, which are highly serum susceptible. Immune responses to bacteremic V. vulnificus infections in human subjects have not been characterized. Serum from a patient who survived sepsis caused by V. vulnificus had substantial bactericidal and opsonizing immunoglobulin G (IgG) for his own bloodstream isolate. Killing was mediated by the classical complement pathway, whereas opsonization was effected by either the classical or the alternative pathway. IgG that reacted strongly with 55-, 58-, and 68-kilodalton outer membrane proteins was present in the patient's convalescent-phase serum but was absent from normal human serum. These findings suggest that humoral immunity to V. vulnificus, mediated by bactericidal and opsonizing antibody, emerges during infection and may be due, in part, to IgG directed against identifiable outer membrane proteins.

Antibodies, Bacterial↗
PubMed1986

Human alveolar lining material and antibacterial defenses.

To investigate the possible antibacterial properties of human alveolar lining material (ALM), we obtained ALM and pulmonary alveolar macrophages (PAM) by bronchoalveolar lavage of healthy nonsmokers. Alveolar lining material was isolated by centrifugation or micropore filtration; electron microscopy revealed lamellar bodies, and lipid analysis showed that 98% of the lipid fraction was phospholipid. No free fatty acids were detected. Streptococcus pneumoniae and non-typable Haemophilus influenzae (NTHI) died spontaneously in PBS at a mean rate of log10 0.75 and 0.95 in 90 min, respectively; the addition of ALM appeared to exert a slight protective effect, and at higher concentrations supported replication of NTHI. There was no difference in the uptake of the bacteria by PAM when ALM was present. Phagocytosed NTHI were killed rapidly and completely within 60 min by PAM with or without ALM. A greater proportion of S. aureus were killed by PAM alone than in the presence of ALM. Alveolar lining material from healthy humans thus appears to have no demonstrable effect on host defense against these bacteria. The differences between our results and those of earlier studies using ALM from rats may relate to interspecies differences in the composition of ALM.

Cholesterol↗
PubMed1986

Isolated C-2 osteomyelitis of hematogenous origin: case report and literature review.

A case of hematogenous Staphylococcus aureus osteomyelitis isolated to the 2nd cervical vertebra is presented. To our knowledge, this is the second case to be reported of hematogenous infection involving only the body and odontoid process of the axis. The first report was published prior to the advent of computed tomography, bone scans, and halo orthosis. The pathophysiology of blood-borne atlantoaxial infection is described, as well as methods of diagnostic evaluation and therapeutic recommendations. The use of computed tomography to define the extent of the lesion is illustrated.

Adult↗
PubMed1986

Recurrent Nocardia pneumonia in an adult with chronic granulomatous disease.

The diagnosis of chronic granulomatous disease was made for the first time in a young adult when he presented with Nocardia asteroides pneumonia. Treatment with trimethoprim/sulfamethoxazole for 10 wk brought about an apparent cure of the infection. Two and one half years later N. asteroides pneumonia recurred and resulted in death from respiratory failure. Antibiotic susceptibility studies suggested that both episodes were caused by the same organism. This suggestion was supported by endonuclease restriction analysis, which showed that the plasmids from both Nocardia isolates were identical. Late recurrence of pneumonia caused by N. asteroides occurs only rarely. In this patient, recurrent infection appeared to be related to persistence of colonizing organisms in the host.

Adult↗
PubMed1985

Spinal epidural abscess.

Spinal epidural abscess is an uncommon and serious infection resulting from direct extension of a local process or hematogenous spread from an antecedent or ongoing distant focus of infection. The findings of spinal ache, tenderness, and fever should suggest the diagnosis, and the appearance of weakness and loss of sensation below the area of pain should be considered as the strongest possible clinical confirmation. In cases in which this constellation of findings occurs, rapid evaluation and immediate surgical decompression and drainage offer the patient a possible successful functional recovery. Even in recent series, permanent paralysis and death occur with unfortunate frequency, and these have usually been related to delay in diagnosis and definitive surgical therapy.

Abscess↗
PubMed1985

Phagocytosis and killing of Brucella by human polymorphonuclear leukocytes.

Although cellular immunity involving activated macrophages is important in resistance to Brucella, serum factors and polymorphonuclear leukocytes (PMNLs) play some role in the initial response to infection. The interaction between human PMNLs and virulent and attenuated strains of Brucella abortus and Brucella melitensis was studied by in vitro techniques. Virulent and attenuated strains of both species were rapidly phagocytosed after opsonization with normal human serum (NHS); nonopsonized bacteria were not phagocytosed. In contrast, NHS devoid of detectable antibodies was bactericidal for strains of B. abortus but not of B. melitensis. In addition, intracellular killing of ingested bacteria was shown for virulent B. abortus but not for B. melitensis. Ultrastructural studies revealed morphological alterations in about one-half of phagocytosed B. abortus and B. melitensis after incubation for 10 min; thereafter, nearly 100% of B. abortus showed some degree of degeneration, whereas B. melitensis remained intact during 120 min of observation.

Adult↗
PubMed1985

Development of bactericidal antibody during Branhamella catarrhalis infection.

The recent observation that Branhamella catarrhalis may cause a variety of infections in humans has stimulated interest in human host defenses against this organism. We encountered 21 patients with B. catarrhalis infection: seven with pneumonia, 13 with a purulent exacerbation of chronic bronchitis, and one with purulent sinusitis. Normal human serum (NHS) demonstrated no bactericidal activity against 20 of the 21 isolates. In contrast, 7 of 19 acute and 18 of 20 convalescent sera demonstrated significant bactericidal effects against the corresponding B. catarrhalis isolate. Heating convalescent sera to 56 C for 30 min abolished bactericidal activity. This activity was restored by NHS but not by complement-rich guinea pig serum. Selective blockage of the classic complement pathway eliminated bactericidal activity, whereas selective blockage of the alternative pathway did not. IgG isolated from convalescent serum plus NHS was bactericidal for the corresponding B. catarrhalis isolate. These results suggest that most patients with pulmonary infections due to B. catarrhalis develop a convalescent IgG antibody response that mediates serum bactericidal activity by the classic complement pathway.

Acute Disease↗