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Biomedical subjects

B F Mackler

Publications and source records attributed to B F Mackler.

At least 19 recordsLinked to original sources

A comparison of the reactivity of Eubacterium species with localized and serum immunoglobulins from rapidly progressive and adult periodontitis patients.

Immunoglobulins in sera and in supernatant fluids of explant cultures of diseased gingival tissues from 20 rapidly progressive and 20 adult periodontitis sites were tested by an ELISA assay for reactivity with typed strains of Eubacterium alactolyticum, E. brachy, E. limosum and E. nodatum. Immunoglobulins present in tissue culture fluids from both rapidly progressive and adult periodontitis samples reactive with E. brachy and E. nodatum were significantly greater (P less than 0.05) than those reactive with E. alactolyticum or E. limosum. The titers to E. brachy in tissue culture fluids from adult periodontitis were significantly greater (P less than 0.05) than those from rapidly progressive periodontitis; there was no difference in titers to the other three species. The only significant difference in serum titers was that sera from patients with rapidly progressive periodontitis had significantly greater reactivity to E. alactolyticum than did sera from adult periodontitis patients. These data indicate that immunoglobulins in the sera of rapidly progressive and adult periodontitis patients do not necessarily reflect the reactivity of localized immunoglobulins present in the diseased gingival tissue explant culture fluids from these patients.

Adolescent

Further studies on the structural requirements for polypeptide-mediated histamine release from rat mast cells.

Structure-activity studies have been performed on a series of naturally occurring and 'tailor-made' polypeptides, by measurement of ability to induce selective histamine release from normal rat peritoneal mast cells in vitro. Compounds investigated include corticotropin and melittin derivatives, mast-cell-degranulating peptide from bee venom, polymyxin B, bradykinin and various synthetic poly(amino acids) and short-chain peptides. It was confirmed that a cluster of four basic residues (lysine or arginine) was optimal for histamine release by corticotropin and melittin polypeptides, provided that the C-terminal carboxyl group was substituted (by, for instance, amidation). In contrast, the presence of a free C-terminal carboxyl group or nearby dicarboxylic acid residues led to a considerable diminution in histamine-releasing activity. Likewise, polypeptides comprised essentially of acidic amino acids were inactive. On the basis of these observations it has been possible to predict that synthetic peptides comprising a particular sequence within the Fc region of human immunoglobulin E, the immunoglobulin class particularly involved in mediation of allergic reactions of the immediate type, would possess potent histamine-releasing activity when similarly made to react with normal rat mast cells. The further study of such a structure should throw new light on the molecular basis of allergen-antibody triggering of mast cells.

Adrenocorticotropic Hormone

Comparison of the plaque microflora in immunodeficient and immunocompetent dental patients.

The nature and extent of the immune dysfunctions in 20 immunodeficient patients, as well as the immunocompetence of 22 control subjects, were verified by cell-mediated responsiveness and immunoglobulin quantitations. Comparisons of the microbial composition of supragingival plaque between the two populations showed that a greater number of immunodeficient than control subjects harbored Candida sp. and Staphylococcus sp. Conversely, a lower number of immunodeficient than control subjects harbored Streptococcus mutans. Also, patients with immune dysfunctions had a lower dental caries experience than their immunocompetent counterparts.

Antibody Formation

IgG subclasses in human periodontal disease. II. Cytophilic and membrane IgG subclass immunoglobulins.

Lymphocyte membrane-associated IgG subclass antibodies in human periodontal disease were studied to ascertain the relative presence of cytophilic IgG antibodies and the membrane Fc receptors which bind them. The experimental approach correlated the effect of incubating gingiva in tissue culture medium to remove cytophilic antibodies with the changes in the number of Fc receptors detectable after washing. The evidence indicated that the majority of lymphocytes in mild gingivitis lesions lacked cytophilic IgG antibodies as well as Fc recetors. In severe gingivitis, the number of IgG subclass bearing lymphocytes increased to about half of the total lymphoid population, while the percentage of Fc receptor bearing cells remained quite low (12.3 % +/- 3.2, S.E.). The majority of IgG subclass bearing lymphocytes had membrane IgG which serve as receptors for antigen; such cells are classically defined as bone marrow (B) derived lymphocytes and serve as the progenitor for plasma cells. Gingival specimens for patients with periodontitis were found to contain the highest percentage of Fc receptor bearing lymphocytes (38.3% +/- 12.6 S.E.) and cytophilic IgG antibodies. The findings indicate that the clinical stages of human periodontal disease are characterized by different populations of infiltrating lymphocytes.

Gingiva

A longitudinal study of T and B lymphocytes from a three-year-old patient with severe combined immunodeficiency (SCID) in 'gnotobiotic protection'.

Fluctuations in the percentages and absolute numbers of T and B lymphocytes were observed in the peripheral blood of a patient with severe combined immunodeficiency maintained in a gnotobiotic environment. Up to 24 months of age, 72-86% of the lymphocytes had surface membrane immunoglobulin (SMIg), 37-47% bore a receptor for C3(EAC-RFC), and 3-12.5% formed spontaneous rosettes with sheep erythrocytes (E-RFC). These values persisted until 30 months, after which shifts in the percentages and absolute numbers of T and B cells were observed. A significant decrease in the proportion of SMIg-bearing cells to 20-40% (169-405 mm3), and EAC-RFC to 10.5-39% (114-259 mm3), was accompanied by a general increase in the proportion of T cells to 19-60% (141-1026 mm3), representing a lymphoid subpopulation approach to normal levels.

B-Lymphocytes

T lymphocyte induction of non-T cell-mediated nonspecific cytotoxicity. I. Introduction mechanisms.

Mononuclear cells (MNC) from normal humans consistently failed to give nonspecific cytotoxic responses. However, after removal of T cells by sheep erythrocyte (E) rosetting, the remaining non-RFC (rosette-forming cells) now gave significant nonspecific cytotoxic responses against both autologous and allogeneic target cells. Reconstitution experiments with T cell subpopulations failed to suppress these nonspecific non-E-RFC-mediated cytotoxic responses. There was also no evidence to indicate the involvement of antibody in this nonspecific cytotoxicity. The cytotoxic cells were characterized as non-E-rosetting, non-phagocytic, and glass adherent lymphocytes; no evidence of monocyte-macrophage participation was found. The inductive trigger of non-E-RFC-mediated cytotoxicity was found to be soluble factors released by T cells during E-rosette formation at 4 degrees C. Incubation of MNC with horse, marmoset and human erythrocytes under identical conditions failed to trigger cytotoxicity. The incubation of quiescent MNC with E-rosetting supernatants (ERS) induced nonspecific cytotoxic responses equivalent to those mediated by separated non-E-RFC. ERS-activated MNC destroyed both autologous and allogeneic target cells. The ERS supernatants themselves were not cytolytic. These findings suggested that cell separation procedures, and possibly in vivo events, which activate T cells may also induce non-T cell-mediated nonspecific cytotoxicity.

Animals

Honey bee venom melittin: correlation of nonspecific inflammatory activities with amino acid sequences.

The nonspecific (nonallergic) inflammatory activity of melittin, a protein toxin from honeybees, was correlated with specific amino acid sequences. Two different amino acid sequences of melittin were found to contribute to nonspecific inflammatory activities in guinea pig skin. Carboxy terminal peptide sequences of 7--10 amino acids induced immediate inflammatory reactions that reached maximum intensities by 15--30 min, then rapidly dissipated. The amino (N) terminal hydrophobic sequence, although not directly inflammatory, intensified the immediate reaction, causing a severe lesion evident by 2 h and characterized by massive polymorphonuclear leukocyte infiltration. A conceptual model of bee venom-induced inflammation in nonallergic individuals is suggested.

Amino Acid Sequence