D K Goroff

Harvard Medical School, Boston, Massachusetts, United States

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Publications (9)48.55 Total impact

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    ABSTRACT: Acute- and convalescent-phase sera from 34 children and 10 young adults were studied to determine if, at what age, and to which antigens of Neisseria meningitidis they respond during disseminated disease. Seven children older than two years of age who were infected with group C or Y strains developed significant increases in both binding and bactericidal antibody. Children infected with group B strains infrequently (eight [31%] of 26) had measurable increases in serum antibody to this capsular polysaccharide; response was meager when it did occur, was unrelated to age, and was considerably poorer than that of young adults, of whom 80% responded. Convalescent-phase sera from all children contained bactericidal antibody. Binding capacity for group B polysaccharide accounted for only 35% of the bactericidal activity in convalescent-phase sera of children infected with group B strains. Bactericidal antibody in the sera of children who did not respond to capsular polysaccharides was often to a lipooligosaccharide antigen.
    The Journal of Infectious Diseases 08/1984; 150(1):71-9. · 5.85 Impact Factor
  • J M Griffiss, D K Goroff
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    ABSTRACT: Circulating IgA which does not bind the first component of complement (C) and does not activate the classical C pathway, blocks the initiation of C-mediated immune effector mechanisms. In at least two clinical situations, epidemic meningococcal disease and severe hepatic dysfunction, IgA blockade of one such mechanism, immune lysis, results in susceptibility to hematogenous bacterial dissemination. The presence of strain-specific IgM, but not IgG, in the sera of susceptibles at the time of dissemination suggested that IgA blockade of IgM-initiated lysis involves a separate mechanism more sensitive to quantitative changes than that involved in IgA blockade of IgG-initiated lysis. We report here that whereas IgA blockade of IgG-initiated immune lysis is a competitive function of the ratio of IgA to IgG, the blocking of IgM-initiated lysis is a noncompetitive function of the ratio of IgA to target cells, independent of the concentration of IgM. In the presence of sufficient IgA to saturate binding sites, IgM is an impotent bystander unable to compete for sites or initiate lysis. Therefore, C-mediated effector mechanisms are more sensitive to quantitative changes in circulating IgA and target cells (binding sites) in the absence of IgG than in its presence. Neither mechanism appears related to binding kinetics.
    The Journal of Immunology 07/1983; 130(6):2882-5. · 5.52 Impact Factor
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    J M Griffiss, D K Goroff
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    ABSTRACT: An immunological cross-reaction between agarose, a naturally occurring galactan, and an antigenic determinant which is a locus for human bactericidal antibody within the LPS of group Y strains of N. meningitidis was investigated. Bactericidal antibody in the convalescent serum of a child from whom a group Y, type IX strain was isolated could be absorbed by highly purified agarose in bead form (Sepharose), but not by a dextran gel (Sephadex). It was inhibited by agarose as a linear polymer and by the strain's LPS, but not by a heterologous LPS from a group B, type II strain of N. meningitidis, nor by the homologous capsular polysaccharide. Both LPS contained galactose; neither was anti-complementary. Agarose antiserum, raised in a rabbit, was bactericidal for the group Y strain, but not for the group B strain. Bactericidal activity in the agarose antiserum could be inhibited by agarose. Immunization with agarose induced haemagglutinating antibody against the group Y strain's LPS which could be absorbed by the group Y, but not the group B strain, and could be reduced by absorption with Sepharose. Absorption with Sepharose also removed the lytic activity against group Y strains of serotypes II and IV from a normal human serum without group Y capsular polysaccharide antibody. We conclude that the cross-reaction resides in the fine structure of the galactose constituent of the group Y strains' LPS.
    Clinical & Experimental Immunology 02/1981; 43(1):20-7. · 3.41 Impact Factor
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    ABSTRACT: A single strain (8021) of Neisseria meningitidis, isolated from a child with disseminated meningococcal disease, was found to elaborate two serogroup-specific capsular polysaccharides-Y and W135. The original isolate as well as the progeny of ten single colony sub-isolates each agglutinated with both group Y and group W135 serogrouping antisera. The capsular polysccharide of strain 8021 contained the chemical constituents of both the W135 and Y capsular polysaccharides in a ratio of about 2.5:1. The patient responded immunologically to both capsular polysaccharides with haemagglutinating antibodies. Analysis by double diffusion in agar revealed that the capsular polysaccharide of strain 8021 contained individual molecules of group W135 and group Y capsular polysaccharides as well as a mosaic molecule containing both antigenic determinants.
    Journal of general microbiology 06/1980; 118(1):39-43.
  • D L Kasper, D K Goroff, C J Baker
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    ABSTRACT: Three polysaccharides were purified from a type III strain of Group B Streptococcus grown under conditions varying in exposure to acid by washing the cells with an EDTA buffer or extracting with cold 10% TCA. Extraction of cells grown in a medium buffered with a pH titrator resulted in a polysaccharide antigen of 1.2 × 106 daltons having only type III serologic specificity. The antigen extracted with EDTA from cells grown in a medium where acid accumulated had a molecular size of approximately 600,000, and demonstrated both type III and group B serologic activity. The antigen extracted with TCA had a molecular size of approximately 500,000 and also reacted with type III and group B sera. Chemical studies revealed that all three polysaccharides contained varying concentrations of galactose, glucose, glucosamine, and sialic acid. Only the TCA antigen contained rhamnose. Alcohol fractionation of the TCA antigen allowed separation of type III from group B serologic reactivity. However, this method failed to separate the two determinants of the EDTA-non-pH titrated antigen. Other physical, chemical, and immunologic methods similarly failed to separate these two determinants. Mild hydrolysis of the EDTA-pH-titrated antigen exposed a determinant immunologically identical to the formamide-extracted group B antigen. These studies as well as electron microscopy and affinity chromatography demonstrated that two determinants exist on the native polysaccharide antigen of type III, Group B Streptococcus. One is the superficial capsular type specific determinant, which in the most native state masks the second determinant, a common group B determinant. Quantitative precipitation inhibition studies confirmed that l-rhamnose was the immunodominant sugar for the formamide-extracted B antigen. No monosaccharide inhibited the cross-reactive determinant on the EDTA-non pH titrated antigen. Despite this observation, both the formamide-extracted B antigen and the EDTA-non pH titrated antigen were demonstrated to be precipitating antibodies of identical specificity.
    The Journal of Immunology 10/1978; 121(3):1096-105. · 5.52 Impact Factor
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    ABSTRACT: The development of antibody in response to invasive infection with type III strains of group B Streptococcus was studied in sera from 31 infants and 4 adults by means of a quantitative radioactive antigen-binding assay. Low concentrations of antibody were consistently found in the acute sera of patients who developed clinical illness. Although adults with puerperal sepsis and infants with bone or joint infection uniformly demonstrated significant rises in serum antibody concentration after recovery, much lower levels of antibody were detected in convalescent sera from infants recovering from meningitis or sepsis. The median antibody concentration in sera from 43 parturients with type III strains of group B Streptococcus isolated from vaginal cultures whose neonates failed to develop symptomatic disease was significantly greater than that in sera from 29 mothers of infants with invasive, type III, group B streptococcal infection. Study of paired maternal and cord sera demonstrated a significant correlation between the antibody concentration in a mother's serum and that in her neonate.
    Journal of Clinical Investigation 06/1977; 59(5):810-8. · 12.81 Impact Factor
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    ABSTRACT: Vaginal specimens for culture of group B Streptococcus and anonymous questionnaires were obtained from 499 college women. Group B Streptococcus was isolated from 90 (18.0%) of the participants. A selective broth medium was more sensitive for detection of vaginal isolates (85 of 493; 17.2%) than was direct inoculation of blood agar plates (44 of 466; 9.4%). The most prevalent serotypes among the isolates were type III (37.9%) and type II (25.3%). Logit analysis identified four factors associated with a higher prevalence of vaginal colonization with group B Streptococcus. These organisms were isolated significantly more often from (1) women who had an intrauterine device (50% vs. 18.6%; P less than 0.001), (2) sexually experienced women (20% vs. 7.1%; P less than 0.02), (3) women studied during the first half of the menstrual cycle (26.5% vs. 14.5%; P less than 0.01), and (4) women 20 years of age or younger (21.4% vs. 14.8%; P less than 0.05). The prevalence of colonization with group B Streptococcus was not related to sexual practices, history of venereal disease, use of oral contraceptives, presence of gynecologic symptoms, use of antibiotics, race, educational level, marital status, or history of pregnancy.
    The Journal of Infectious Diseases 04/1977; 135(3):392-7. · 5.85 Impact Factor
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    ABSTRACT: An opsonophagocytic assay has been developed which requires human polymorphonuclear leukocytes, immune serum, and complement for optimal killing of Group B streptococci. Only with all three of these components was killing of greater than 1.0 log10 of the initial inoculum achieved, using rabbit antisera directed to homologous strains of each of the five known serotypes of Group B streptococci. Titers of specific antisera which opsonized the strains and resulted in greater than 1 log 10 reduction of colony-forming units, ranged from 1:100 (serotype Ib) to 1:3200 (serotype Ia). Cross-reactions between serotype-specific sera and heterologous strains were seen in certain instances. Type Ic strain and serotype Ic antiserum demonstrated cross-reactions with types Ia and Ib which were explainable by known shared antigens among these types. The only other cross-reaction which resulted in greater than 1 log 10 reduction in colony-forming units was when unabsorbed antiserum to strain Ia was used to opsonize a strain of serotype III. Opsonization of 10 serotype III strains was demonstrated with a single type III antiserum. Killing of nine of these strains required polymorphonuclear leukocytes, complement, and antiserum, but one strain, D136C, the reference strain, could be killed (greater than 1 log 10 reduction in colony-forming units) without either complement or specific antiserum. Inhibition studies were performed utilizing large m.w. polysaccharide antigens extracted from each serotype. These antigens inhibited opsonization of homologous strains by homologous antisera with 50% inhibition points ranging between 0.5 and 4 mug.
    The Journal of Immunology 03/1977; 118(2):673-8. · 5.52 Impact Factor
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    ABSTRACT: Three bacteriological techniques for the isolation of group B streptococci in vaginal cultures were compared. A selective broth medium (SBM) containing gentamicin and nalidixic acid was more sensitive for the detection of vaginal isolates (28/76, 36.8%) from 76 women enrolled in a venereal disease clinic than was an identical selective plate medium (SPM) (17/76, 25%). Similarly, SBM allowed identification of positive cultures from college women (82/459, 17.9%) significantly more often than direct inoculation of swabs onto nonselective blood agar medium (43/460, 9.4%; chi2 = 42.2, P = less than 0.001). Failure to isolate group B streptococci detected in SBM occurred in 32.1% cultures by SPM and 49.4% of cultures by nonselective agar medium. Multiple serotypes were detected in a single vaginal culture from approximately 5% of the patients studied. These data support the routine use of SBM for the most accurate identification of women vaginally colonized with group B Streptococcus.
    Journal of Clinical Microbiology 08/1976; 4(1):46-8. · 4.07 Impact Factor