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Biomedical subjects

D M Musher

Publications and source records attributed to D M Musher.

At least 145 records · Page 8Linked to original sources
PubMed1985

Phagocytosis and killing of common bacterial pathogens of the lung by human alveolar macrophages.

To investigate factors that determine susceptibility of the lungs to infection with common respiratory pathogens, we studied phagocytosis and killing of nontypable Haemophilus influenzae, H. influenzae type b, Streptococcus pneumoniae types III, VI, and XIV, an unencapsulated variant of S. pneumoniae type III, and Staphylococcus aureus Cowan I, by using human alveolar macrophages obtained by bronchoalveolar lavage of healthy nonsmokers. After opsonization with 10% pooled human serum, mean uptake (+/- standard deviation) of nontypable H. influenzae (67.5% +/- 15.0%), unencapsulated S. pneumoniae type III (71.2% +/- 4.8%) and S. aureus (79.1% +/- 10.2%) was significantly greater (P less than .01) than that of H. influenzae type b (40.1% +/- 15.0%), and S. pneumoniae types III (4.4% +/- 3.1%), VI (11.8% +/- 9.6%), or XIV (8.7% +/- 7.0%). Nontypable H. influenzae was ingested after opsonization with much less pooled human serum than was H. influenzae type b, and uptake of encapsulated S. pneumoniae was not enhanced by as much as 80% pooled human serum. Intracellular killing of unencapsulated S. pneumoniae type III and nontypable H. influenzae was rapid and complete and corresponded to the degree of phagocytosis, but despite a high uptake, S. aureus were killed slowly and incompletely. The virulence of S. pneumoniae and H. influenzae as lung pathogens is thus determined jointly by encapsulation and the inadequate opsonizing effect of normal human serum, whereas that of S. aureus may be related to the organism's relative resistance to intracellular killing by alveolar macrophages.

Antibodies, Bacterial↗
PubMed1985

Outer membrane proteins of nontypable Haemophilus influenzae and reactivity of paired sera from infected patients with their homologous isolates.

Normal human serum and acute or convalescent serum from patients infected with nontypable Haemophilus influenzae were tested for reactivity with electroblotted outer membrane proteins obtained from the homologous nontypable H. influenzae isolates. Of 12 patients, 8 had immunoglobulin G antibodies to outer membrane proteins from their own infecting nontypable H. influenzae isolates that were not present in normal human serum. Three patients had immunoglobulin antibody in convalescent serum that had been absent in acute serum, but no consistent outer membrane protein was involved in the sets of patient sera with outer membrane proteins examined.

Antibodies, Bacterial↗
PubMed1985

Radioimmunoassays for the detection of antibodies to treponemal polypeptide antigens in serum.

Cross-reacting treponemal antigens are potentially important candidates for serodiagnostic assays in syphilitic infections. Based on the idea that the organelles for locomotion in virulent and avirulent treponemes might be composed of similar subunits, we attempted to purify the flagellar antigens of Treponema phagedenis biotype Reiter and Treponema refringens for use in radioimmunoassays. With a combination of physical and chemical methods, the major protein subunit of purified flagellar preparations exhibited a mass of approximately 37 kilodaltons (kd) on sodium dodecyl sulfate-polyacrylamide gels. These 37-kd materials, with weight estimates comparable to those of other flagellin molecules, were further purified by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroelution. Human and rabbit sera, alone or subjected to DEAE Affi-Gel blue chromatography, were subsequently tested in radioimmunoassays employing each of the purified preparations. Even though sera from patients with secondary syphilis and from experimentally infected animals at 3 to 4 weeks postinfection were reactive in radioimmunoassays employing the 37-kd flagellar antigens, the assays were relatively insensitive for detection of immunoglobulin G responses in the early stages of human infection. Detection of immunoglobulin G antibodies in sera obtained early in the course of natural or experimental infection was possible with electroeluted 33- to 64-kd materials from both avirulent and virulent treponemes.

Animals↗
PubMed1985

Amebiasis presenting as pleuropulmonary disease.

Seven patients with amebic liver abscess presenting as pleuropulmonary disease were admitted to hospital initially because of pulmonary symptoms and were found to have amebic liver disease. Three categories of pleuropulmonary involvement included reactive inflammation of the pleura or lung, rupture of a hepatic abscess into the pleural space and rupture of a hepatic abscess into the bronchial airways. The preferred medical treatment is with metronidazole, but rupture of hepatic amebic abscess into the pleural space requires drainage in addition to medical therapy. In contrast, rupture into the bronchus may provide spontaneous drainage so that only medical therapy is needed. Recovery from amebiasis in all three categories is generally complete. Morbidity and mortality increase with failure to correctly identify amebic infection of the liver as the underlying cause. Because, in new cases, no findings specifically suggest that pleuropulmonary disease is a complication of hepatic amebic abscess, this possibility needs to be considered, especially in persons who are at risk of having been infected with amebae.

Adult↗
PubMed1984

Resistance of Vibrio vulnificus to serum bactericidal and opsonizing factors: relation to virulence in suckling mice and humans.

Vibrio vulnificus causes soft-tissue infections, gastrointestinal disease, and severe sepsis in humans. Bacterial and host factors in virulence have remained poorly defined. We found that blood culture isolates of V. vulnificus were completely resistant to the bactericidal effects of 10% normal human serum, in contrast to soft-tissue and environmental isolates that showed a mean 2.6 log10 decline during 120 min of incubation. Following opsonization by 10% normal human serum, mean uptake of blood isolates by normal human polymorphonuclear leukocytes during 20 min of incubation in vitro was 45.8% compared with 83.2% for isolates from other sites. Blood isolates were lethal for suckling mice (mean LD50, 1.3 X 10(6)) in contrast with isolates from other sites, which were less virulent (mean LD50, 1 X 10(9)); lethality correlated well with bacteremia at 6 hr. These studies show a close correlation between bacterial virulence for humans and suckling mice and suggest that resistance to the bactericidal and opsonizing effects of normal human serum may be important factors governing that virulence.

Adult↗
PubMed1984

Evaluation of Sch 29482 in experimental syphilis and comparison with penicillin G benzathine in disseminated disease and localized infection.

The present study was designed to assess the in vivo activity of Sch 29482, a new penem antibiotic, against disseminated and localized Treponema pallidum infections in rabbits. Animals were inoculated either intravenously or intradermally. Randomized groups then received 25 or 50 mg of Sch 29482 per kilogram of body weight twice a day for 7 days, two weekly injections of 200,000 U of penicillin G benzathine for comparative purposes, or no antibiotic therapy. In both infection models, striking differences were noted between the untreated control rabbits and rabbits receiving penicillin G benzathine or high-dose Sch 29482. Intravenously infected rabbits did not develop disseminated lesions or orchitis, and chancres produced by intradermal infection regressed and healed rapidly after both treatment regimens. Infectivity studies also suggested that high-dose Sch 29482 and penicillin G benzathine were effective since the testes and lymph nodes of treated animals were free of infectious organisms. Treatment of animals with the lower dose of Sch 29482 represented borderline or suboptimal therapy, with a failure rate of one in four for each infection model.

Animals↗
PubMed1984

Immunoglobulin A from bronchopulmonary secretions blocks bactericidal and opsonizing effects of antibody to nontypable Haemophilus influenzae.

Patients with chronic bronchitis are colonized by and may develop acute bronchopulmonary infection due to nontypable Haemophilus influenzae (NTHI) despite the presence of bactericidal and opsonizing antibody to the infecting organism. To test the hypothesis that secretory immunoglobulin A (IgA) interferes with host defense mechanisms, we extracted secretory IgA from bronchopulmonary secretions of five patients with NTHI pneumonia. NTHI was incubated with IgA before or during incubation with each patient's own serum or normal human serum. IgA from four of these individuals blocked the bactericidal and opsonizing effects of normal human serum and/or their own serum against their own and/or other NTHI. IgA from bronchopulmonary secretions of patients not infected with NTHI or from the serum of a patient with an IgA myeloma had no such effect. Blocking appeared to result from a direct interaction between IgA and the bacteria. The presumed mechanism is an interaction with bacterial surface antigens, although it is not known whether this occurs at antigenic sites responsible for bactericidal and opsonizing activity or whether interaction with adjacent antigenic sites and subsequent steric interference is responsible. This blocking effect of IgA may be one mechanism that allows for the development of NTHI colonization or pneumonia in an individual who already has seemingly adequate antibody against the infecting organism.

Antibodies, Bacterial↗
PubMed1983

Fees.

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Fees, Medical↗
PubMed1983

Haemophilus influenzae infections.

Of the six typeable strains of this organism, type b is the most virulent, accounting for 95% of serious infections in children. Unexpectedly, in adults, nearly two thirds of isolates from blood and CSF were found to be nontypeable. The spectrum of clinical disease associated with type b and nontypeable strains is discussed. Effective immunization of infants is now in the planning stages.

Adult↗
PubMed1983

The interaction between Treponema pallidum and human polymorphonuclear leukocytes.

The interaction between polymorphonuclear leukocytes (PMNLs) and Treponema pallidum was studied. Intradermal injection of greater than or equal to 10(6) T. pallidum into rabbits caused a rapid accumulation of PMNLs. Human serum released chemotaxigenic factor (C5a) during incubation in vitro with T. pallidum. Incubation of T. pallidum with human PMNLs in vitro (ratio, 100:1) stimulated chemiluminescence. These responses were dependent upon the presence of both antibody and complement and were greatest when serum from a patient with late secondary syphilis was used as a chemotaxigenic source or for opsonization. Electron microscopic studies documented the rapid uptake of T. pallidum into membrane-bound vacuoles in the human PMNLs in vitro after incubation for as little as 5 min, with leukocyte degranulation and loss of treponemal integrity observed after 4 hr. T. pallidum were found within PMNLs 3 hr after intradermal inoculation of rabbits. These data show that PMNLs are attracted to, and appear to ingest, T. pallidum, but they fail to explain why inoculation of these organisms is not followed by eradication.

Animals↗
PubMed1983

Opsonizing and bactericidal effects of normal human serum on nontypable Haemophilus influenzae.

The observation that nontypable (NT) Haemophilus influenzae causes serious infection in adults has stimulated interest in mechanisms that may protect the human host against NT H. influenzae infection. Incubating NT H. influenzae with normal human serum (NHS) caused dose- and time-dependent killing that varied with the individual NHS and NT H. influenzae. Adsorption of NHS with NT H. influenzae removed bactericidal activity against the adsorbing isolate but not necessarily that against others, suggesting antigenic diversity and supporting recent studies that show different outer membrane protein profiles among NT H. influenzae. Heating NHS to 56 degrees C for 30 min abolished bactericidal activity; this activity was not restored by complement-rich guinea pig serum or NT H. influenzae-adsorbed NHS. This is analogous to the "third factor" needed for intraleukocytic killing of pneumococci. Optimal opsonization of NT H. influenzae for phagocytosis by human polymorphonuclear leukocytes required antibody and complement, but other serum factors also played a role. Bactericidal activity generally, but not uniformly, correlated with opsonizing activity of individual NHS. Humoral factors may be important in host defenses against NT H. influenzae infection; their emergence during convalescence warrants further study.

Blood Bactericidal Activity↗
PubMed1983

Isolation and preliminary characterization of circulating immune complexes from rabbits with experimental syphilis.

Immune complexes isolated from sera of rabbits with experimental, disseminated syphilis were found to have sedimentation coefficients greater than 19s. By radioimmunoblot assays, materials precipitated with 2.5% polyethylene glycol or chromatographed on DEAE-Affi-Gel Blue were found to contain albumin, C3, immunoglobulin M (IgM), IgG, and treponemal antigen(s), whereas control materials contained only albumin and IgG. When polyethylene glycol precipitation of immune complexes from syphilitic rabbits was followed by immobilization on protein A and acid elution, radioimmunoblots detected only IgG and treponemal antigen(s).

Animals↗
PubMed1983

Circulating immune complexes in experimental syphilis: identification of treponemal antigens and specific antibodies to treponemal antigens in isolated complexes.

As a prelude to characterization of the host and treponemal antigens present in purified immune complexes from the sera of rabbits with disseminated syphilis, autoradiographic and immunoenzymatic analyses of solubilized extracts of Treponema pallidum, Treponema phagedenis biotype Reiter, and Treponema refringens were performed on electroblots of polypeptides first separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Electroblots of purified immune complexes were developed with the same panel of antisera so that protein profiles could be compared. Eight treponemal antigens were consistently present in isolated complexes; four of these cross-reacted with antisera prepared against avirulent treponemes. The average molecular weights of these antigens were 87,000, 76,000, 66,000, and 45,000. Antibodies dissociated from isolated immune complexes, when used for the development of T. pallidum electroblots, reacted with four antigens of comparable molecular weight. Antibodies to those polypeptides were also present in the sera of animals immunized with immune complexes. The demonstration of treponemal antigens in purified immune complexes convincingly argues that their occurrence in experimental syphilis is not merely due to tissue destruction and responses to endogenous host antigens.

Animals↗
PubMed1983

Pneumonia and acute febrile tracheobronchitis due to haemophilus influenzae.

Of 30 patients with pneumonia due to Haemophilus influenzae, 26 had infection due to nontypable and 4 due to typable organisms. Biotype I isolates were implicated with surprising frequency. Blood cultures were positive in six patients. An additional 14 patients, all with nontypable H. influenzae infection, had febrile purulent tracheobronchitis that was clinically indistinguishable from pneumonia except for the absence of a radiographic infiltrate; none were bacteremic. Penicillin susceptibility was shown for 95% of isolates, and response to ampicillin was prompt. Patients had high serum levels of bactericidal antibody on admission but had lower levels of serum opsonizing activity against their own organism than did uninfected carriers with chronic bronchitis; 2 to 3 weeks later, levels of opsonizing antibody had risen to equal those of carriers. Deficient opsonizing activity may have contributed to susceptibility to infection. These findings identify both host and bacterial factors that may cause susceptibility to pulmonary infection from H. influenzae.

Antibodies, Bacterial↗
PubMed1983

Osteomyelitis beneath pressure sores.

Twenty-eight pressure sores were evaluated prospectively. Osteomyelitis was reported histologically in nine of 28 bones and pressure-related changes were reported in 14 bones. Roentgenograms suggested the presence of osteomyelitis in four instances of histologically proved osteomyelitis. Technetium Tc 99m medronate bone scans were highly sensitive, showing increased uptake in all cases of osteomyelitis; however, increased uptake also occurred commonly in uninfected bones due to pressure-related changes or other noninfectious causes. Cultures of bone biopsy samples usually disclosed anaerobic bacteria, gram-negative bacilli, or both. The diagnosis of osteomyelitis must be considered if a pressure sore does not respond to local therapy. If the technetium Tc 99m medronate uptake is increased in the involved area, or roentgenographic findings are abnormal, the diagnosis can only be made with certainty by histologic examination of bone. Antibacterial treatment should be selected based on the results of bone culture.

Adult↗