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Biomedical subjects

A L Bisno

Publications and source records attributed to A L Bisno.

At least 19 recordsLinked to original sources

Human immune response to immunization with a structurally defined polypeptide fragment of streptococcal M protein.

We tested the ability of pepsin-extracted, highly purified M protein to induce type-specific immunity in experimental animals and humans. M protein was prepared from limited peptic digests of whole group A type 24 streptococci and was purified to chemical homogeneity as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, quantitative amino acid analysis, and Edman degradation. For vaccination, the lyophilized M24 protein preparation (pep M24) was precipitated in aluminum hydroxide. When injected into laboratory animals, alum-precipitated pep M24 produced type-specific protective antibodies and was free of non-type-specific immunoreactivity. In man, skin tests with 1-microgram doses of pep M24 were negative in all 37 adults tested. 12 adult human volunteers received two-four subcutaneous injections of 100-200 micrograms of alum-precipitated pep M24 at intervals of at least 2 wk. The immune response to pep M24 was measured by a variety of assays designed to detect (a) type-specific humoral antibodies (opsonophagocytic, long chain, and mouse protection tests); (b) total humoral antibodies (complement fixation and enzyme-linked immunosorbent assay); (c) cellular immunity (skin tests); and (d) heart cross-reactive antibodies (immunofluorescence). Type-specific opsonic antibodies developed in 10 of the 12 vaccinees, and positive delayed-type skin tests developed in 11. Immune sera from two of the vaccinees were effective in mouse-protection tests against challenge with M24 but not M6 streptococci. None of the volunteers developed heart-reactive antibodies or antibodies to non-type-specific M protein antigens. Alum-precipitated pep M24 was well-tolerated in man, and no serious local or systemic reactions were observed. Thus, pep M24 induces type-specific, protective antibodies in doses that are well-tolerated in man.

Adult

Alternate complement pathway activation by group A streptococci: role of M-protein.

Avirulent strains of group A streptococci readily activate the complement system in normal human serum via the alternate complement pathway (ACP). Virulent M-positive group A streptococci are much less potent as activators of the ACP. The ability of M-positive streptococci to activate the ACP is enhanced by trypsinization or mild peptic digestion. The latter treatment removes the serologically active and antiphagocytic type-specific moieties of M protein, but retains the surface fuzzy layer. The phagocytosis of avirulent streptococci is markedly enhanced by preopsonization in serum chelated with Mg-ethylene glycol tetraacetic acid (classic complement pathway blocked) but not in serum devoid of heat-labile factors. These studies suggest that the function of M protein as a virulence factor may be mediated, at least in part, by its ability to retard interaction of ACP components with structures present on the streptococcal cell surface.

Bacterial Proteins

Susceptibility of skin and throat strains of group A streptococci to rosamicin and erythromycin.

The minimal inhibitory concentrations of rosamicin and erythromycin were compared for 210 strains of group A streptococcus isolated from a diverse spectrum of streptococcal diseases. Of these strains, 97.6% were inhibited by 0.1 to 0.2 mug of rosamicin per ml, whereas 90.9% were inhibited by 0.025 to 0.05 mug of erythromycin per ml. The minimal inhibitory concentration of rosamicin for 154 strains exceeded that of erythromycin by at least fourfold. Five group A strains of streptococcus that were highly resistant to erythromycin were even more resistant to rosamicin.

Aminoglycosides

Antigens in urine of patients with glomerulonephritis and in normal human serum which cross-react with group A streptococci: identification and partial characterization.

Hyperimmune rabbit antisera antisera against group A streptococci precipitate protein antigens present in the urines of patients with poststreptococcal AGN and other glomerulopathies and also present in normal human serum. Over 90% of patients with AGN excrete detectable amounts of cross-reactive antigens in their urines, as do approximately 20% of patients with nonstreptococcal glomerulopathies. The streptococcal antigens are present in culture supernates, and immunodiffusion reactions in agar gel show identity or partial identity of serum, urine, and streptococcal antigens with antisera prepared against either urine proteins or against whole group A streptococci. Cross-reactive antibodies are removed from rabbit antisera by absorption with streptococcal culture supernates but not by absorption with a variety of streptococcal somatic constituents. The cross-reactive antigens have been isolated from streptococcal cultures grown in synthetic medium, thus eliminating the possibility of artefact due to tissue antigens present in Todd-Hewitt broth. The principal antigens have now been purified both from AGN urine and streptococcal supernates by molecular sieve and ion-exchange chromatography. They both have a molecular weight of approximately 360,000 daltons, as estimated on columns of agarose. The urine antigen has been applied to SDS-PAGE, and the migration of the major band was consistent with a molecular weight of 85,000 daltons. Rabbit antiserum to purified urine antigen precipitates both AGN urine and streptococcal supernates. These newly recognized human antigens, which cross-react with group A streptococcal antigens, are of particular interest because of their presence in readily available biologic fluids and their preferential excretion in almost all patients with poststreptococcal AGN.

Antigens, Bacterial

Streptococcal infections that fail to cause recurrences of rheumatic fever.

Prospective studies of recurrences of streptoccal infection and acute rheumatic fever were conducted among patients attending the acute rheumatic fever prophylaxis clinic (City of Memphis Hospitals, Memphis, Tennessee) between 1965 and 1972. The patient population consisted of 124 rheumatic children and adults, two-thirds of whom had evidence of rheumatic heart disease. A total of 104 immunologically documented streptococcal infections occurred during 235 patient-years of follow-up (44.3 infections per 100 patient-years) without a single recurrence of rheumatic fever. Immune responses tended to be modest, and 80% of the infections were subclinical. The majority of our group A streptococcal isolates were obtained from routine cultures of specimens from asymptomatic individuals. Many of these strains were "pyoderma" serotypes, whereas others exhibited a characteristic (production of opacity factor) recently reported to be associated with decreased immunogenicity. Several factors may have contributed to the low recurrence rate of acute rheumatic fever, including the age range of the population under study and immunologically significant infections with strains of Streptococcus that were not group A, but a major reason may be the possibility that the group A strains prevalent in this population have diminished rheumatogenic potential.

Adolescent

Fulminant pneumococcal infections in 'normal' asplenic hosts.

Five asplenic persons with no other detectable underlying disease had over-whelming pneumococcemia. Four of the patients had undergoing splenectomy for trauma, and the fifth had asplenia as an isolated congenital abnormality. Including the cases presented here, there are now at least 26 reported instances of fatal or life-threatening pneumococcal infections in otherwise-normal asplenic patients. Thus, splenectomy per se is associated with an increased risk of over-whelming pneumococcemia. Although the magnitude of the risk is low, mortality associated with these infections is high. Analysis of the clinical data strongly suggests that undiagnosed febrile episodes in asplenic persons should be treated promptly with antibiotics while awaiting culture results. This strategy should be adopted regardless of the age of the patient or his general state of health. The observation that a limited number of pneumococcal serotypes, particularly type XII, appear to predominate in these cases suggests that pneumococcal vaccine might be highly efficacious in preventing overwhelming post-splenectomy pneumococcal infections in otherwise-normal hosts.

Adolescent

Failure of vancomycin treatment in Staphylococcus aureus endocarditis. In vivo and in vitro observations.

In a case of staphylococcal endocarditis, we failed to eradicate Staphylococcus aureus from the blood stream with vancomycin hydrochloride therapy. The strain involved was sensitive to vancomycin by disk diffusion studies but showed a wide disparity between minimal inhibitory and minimal bactericidal concentrations. The lack of a bactericidal effect was probably responsible for the failure of treatment. A synergistic effect was demonstrated for the combination of gentamicin sulfate and methicillin sodium, and the patient was ultimately cured with this combination plus vancomycin. Bactericidal tests are important in choosing an antimicrobial agent for treatment of endocarditis.

Adult

The epidemiology and natural history of streptococcal pyoderma: an endemic disease of the rural southern United States.

In order to study the natural history of endemic pyoderma, the host and environmental risk factors to infection, the immunologic response and the risk of acute glomerulonephritis (AGN) a prospective study was done between June 29 and December 13, 1970 in 444 black children aged 2-6 years attending project Headstart centers in Holmes County, Mississippi. The weekly prevalence of pyoderma was about 40-50% during July and August but decreased to 4% during the last week of the study. "Pyoderma-type" serotypes of group A streptococci were isolated from about 70% of the skin lesions and similar serotypes were also commonly isolated from the pharynx. The seasonal prevalence and T and M typing pattern of most of the pharyngeal isolates mirrored the skin isolates. Many of the streptococci appear to belong to previously unrecognized M-types and one strain has been designated provisional M type 67 by the International Subcommittee on Pneumococci and Streptococci. Staphylococci were also isolated commonly from the skin lesions, especially late in their evolution. Despite an 80% incidence of streptococcal pyoderma during the summer months, only 3 children (0.67%) developed AGN; all of these children had clinically mild disease. The risk of a major outbreak of AGN in populations like these is substantial. Surveillance for clusters of AGN is indicated and widespread benzathine penicillin prophylaxis should be used in the event of an outbreak. Also, further research to determine the long term prognosis of clinically mild AGN and to detect useful laboratory markers of nephritogenicity are indicated.

Age Factors

Nosocomial infection with highly resistant, Proteus rettgeri. Report of an epidemic.

Over 22-1/2 months an epidemic of at least 127 cases of nosocomial infection developed from a strain of Proteus rettgeri resistant to all antibiotics commonly tested in hospital laboratories. Although there were at least four cases of septicemia and one related death, the majority of cases consisted of asymptomatic bacteriuria or clinically mild urinary tract infection. Indwelling urinary tract devices and antibiotic therapy were important predisposing factors. Data supported an association between increasing use of gentamicin and increasing rates of resistant infection. No common source was found, and contact spread appeared more likely. Control measures included efforts to reduce unnecessary exposure to the incriminated risk factors and to improve asepsis in the management of catheterized patients. An additional 36 cases and one related death were identified in the 7-1/2 months following the investigation and institution of control measures. Nosocomial infection with extremely resistant organisms may pose a serious hazard wherever indwelling urinary tract devices and antibiotics are used together intensively.

Bacteriuria

Antigens of group A streptococci involved in passive hemagglutination reactions.

Antibodies to streptococcal extracellular products were detected in rabbit sera by passive hemagglutination tests as early as 1 week after intravenous injection of live group A streptococci (strain C203S). Using these antibodies in immunoadsorbent columns, we prepared an antigenic fraction from crude concentrates of streptococcal extracellular products. The specific activity of this fraction in sensitizing glutaraldehyde-treated erythrocytes for passive hemagglutination tests and in absorbing passive hemagglutination antibodies from immune sera was increased by 80-fold and at least 24-fold, respectively, as compared with crude extracellular products. The fraction has been found to contain at least three serologically active antigens, which are of considerable interest because: (i) they gave rise to early and consistent immune responses both in humans and in experimental animals; (ii) they appear so far to be produced only by beta-hemolytic streptococci; and (iii) antibodies to these antigens are present in high titers in patients with acute rheumatic fever. Our data suggest that passive hemagglutination antigens may be distinct from those extracellular enzymes and hemolysins ordinarily employed in streptococcal serological studies.

Animals