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Biomedical subjects

J A Kazmierowski

Publications and source records attributed to J A Kazmierowski.

At least 19 recordsLinked to original sources
PubMed1984

Dermatitis herpetiformis: effects of sulfones and sulfonamides on neutrophil myeloperoxidase-mediated iodination and cytotoxicity.

The effects of sulfones and sulfonamides on neutrophil myeloperoxidase-mediated iodination and cytotoxicity were studied using in vitro assays to measure these parameters. Leukocyte iodination was documented using a quantitative assay to measure the iodination of protein by human neutrophils undergoing phagocytosis. Cytotoxicity for the tumor cell line LSTRA by human neutrophils activated by exposure to phorbol myristate acetate was measured by a 51Cr release assay. Dapsone, diasone, and sulfapyridine, at concentrations comparable to serum levels obtained by therapeutic doses of drug, effectively inhibited iodination and cytotoxicity mediated by human neutrophils. Other sulfonamides showed little inhibition of either iodination or cytotoxicity. The amount of inhibition was comparable to that seen with the inhibitors azide or cyanide and occurred in a dose dependent manner with all three drugs. A cell-free cytotoxic system using myeloperoxidase, iodide, a H2O2 generating system, and target cells also showed inhibition by dapsone, diasone and sulfapyridine in a similar fashion. The active drugs inhibited both the intra- and the extracellular myeloperoxidase-H2O2-halide cytotoxic systems. Serial iodination studies of four dermatitis herpetiformis patients, evaluated while taking dapsone or sulfapyridine, showed inhibition of iodination by either drug. Levels of IgA immune complexes, as measured by the Raji cell radioimmune assay adapted for IgA, did not change when medication was withheld. These studies demonstrate that dapsone, diasone, and sulfapyridine inhibit both neutrophil iodination and cytotoxicity for tumor cells, while other sulfonamides have no effect. This confirms previous studies showing inhibition by myeloperoxidase mediated iodination by dapsone. Furthermore, the effect on neutrophils is quickly reversible; in vivo administered drug has no effect on in vitro function. The active drugs inhibit both intra- and extracellular cytotoxic systems. This may represent an important mechanism by which these drugs produce their therapeutic effects when used to treat inflammatory skin diseases.

Antigen-Antibody Complex↗
PubMed1983

Immunoregulation in atopic dermatitis: functional analysis of T-B cell interactions and the enumeration of Fc receptor-bearing T cells.

Immune aberrations in atopic dermatitis (AD) are multiple and interrelated. We investigated immunoregulatory cell markers and functional interactions of purified T- and B-enriched cells in a pokeweed mitogen (PWM)-stimulated IgG production assay in patients with AD. Atopic mononuclear leukocytes and autologous recombinations of purified atopic T and B cells were hyporesponsive to PWM stimulation of IgG synthesis. When atopic B cells were cultured with normal T cells, they were still less responsive than normal B cells. Atopic T cells generated normal levels of suppression in three responder systems. Radioresistant T-cell help was also in the normal range whereas nonirradiated AD T cells produced slightly less help than normal T cells. We noted reduced levels of T lymphocytes with FcIgG receptors (T gamma) and found that T gamma reduction correlated inversely with log serum IgE. In the light of normal T suppression, we critically examined AD cell adherence and contamination at various steps in the T gamma assay to rule out technical causes of T gamma reduction in AD. Lowered T gamma cells in AD were not associated with circulating IgG immune complexes and subsequent blockade of the FcIgG receptors. Thus, we have identified defects in the numbers of an immunoregulatory T cell, and in the generation of PWM-responsive B cells. A model is proposed in which the alterations in atopic cyclic nucleotide metabolism of T-cell helpers could result in abnormalities of immunoregulatory T cells and PWM-recruitable B cells.

Adolescent↗
PubMed1982

Herpes simplex antigen in immune complexes of patients with erythema multiforme: presence following recurrent herpes simplex infection.

Serum samples from patients with erythema multiforme (EM) were examined for the presence of herpes simplex virus (HSV) antigen in immune complexes using the Raji cell radioimmunoassay. Raji-cell-bound immune complexes from eight of 12 patients with EM after HSV infection and four of four patients with EM of uncertain cause had increased anti-HSV binding, while patients with EM after drug exposure and patients with recurrent HSV infections without EM had binding in the same range as controls. Viral cultures for HSV of immune complexes eluted from Raji cells were negative. Sucrose density gradient ultracentrifugation studies of serum samples of patients with EM after HSV infection showed HSV antigen in large molecular weight fractions. The HLA typing of lymphocytes from 16 patients with EM after HSV infection was not different from that of controls. Immune complexes composed of antibody and HSV antigen are present in serum samples of patients with EM after HSV infection and some cases of EM of uncertain cause and may mediate the pathogenesis of these disorders.

Antigen-Antibody Complex↗
PubMed1980

Immune complexes in erythema multiforme and the Stevens-Johnson syndrome.

Early cutaneous lesions of erythema multiforme or mucosal lesions of the Stevens-Johnson syndrome contain delicate granular deposits of immune reactants and/or complement components lodged in the walls of vessels of the papillary dermis. Such deposits are not present in normal, unaffected skin although they can be caused to occur there by injection of substances which increase vascular permeability. Factors which cause accumulation of mononuclear cells in the papillary dermis have not been elucidated but we suggest that receptors for the C3d fragment of the third component of complement could be responsible. Factors which cause intercellular edema in the epidermis, epidermal-dermal separation, or necrotic keratinocytes are unknown. We, and others, may now measured immune complexes in the serum of patients experiencing these reaction patterns by means of Raji cell radioimmunoassay, C1q precipitation, 125I-C1q binding, cryoprecipitation and with monoclonal rheumatoid factor. Cryoimmunoglobulins have also been described and antigens of Herpesvirus hominus have been measured in the cryoprecipitate of 2 patients who experienced erythema multiforme following recurrent herpesvirus infection. Erythema multiforme commonly accompanied serum sickness reactions which occurred following injection of immune horse serum in the 1980s (von Pirquet and Schick). Such reactions are now well established as due to circulating immune complexes in antigen excess.

Antigen-Antibody Complex↗
PubMed1978

Dermatologic manifestations of the hypereosinophilic syndrome.

We report the histopathologic and dermatologic manifestations of eight patients with hypereosinophilic syndrome (HES). Skin lesions occurred in eight patients (53%) in a group of 15 patients with HES, and were generally of two types: (1) erythematous pruritic papules and nodules, or (2) urticaria and angioedema. As HES was treated with appropriate therapy, the skin lesions improved. Skin eruption may be the only manifestation of disease in otherwise asymptomatic patients with HES.

Adult↗
PubMed1977

Experimental pneumonia due to Pseudomonas aeruginosa in leukopenic dogs: prolongation of survival by combined treatment with passive antibody to Pseudomonas and granulocyte transfusions.

Treatment with type-specific IgG antibody to Pseudomonas aeruginosa significantly increased rates of survival after experimental induction of pseudomonas pneumonia in leukopenic dogs. Longer survival times were correlated with higher titers of circulating antibody in serum; however, no animals treated with antibody alone were long-term survivors. Subsequent development of sepsis or the recovery of Pseudomonas from infected lung tissue was not altered by treatment with antibody. Therapy with granulocyte transfusions plus gentamicin was associated with a 27% rate of long-term survival. Passive immunization with IgG (reciprocal mean hemagglutination titer, 52) in addition to granulocyte transfusions and treatment with gentamicin resulted in a rate of long-term survival of 67% (P less than 0.05). Dogs that died while receiving this combination therapy still had a survival time significantly longer than those of controls or animals treated only with granulocytes and antibiotic.

Animals↗
PubMed1977

Analysis of cellular and protein content of broncho-alveolar lavage fluid from patients with idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis.

To evaluate cellular and protein components in the lower respiratory tract of patients with idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (CHP), limited broncho-alveolar lavage was done in 58 patients (19 IPF, 7 CHP, and 32 controls). Analysis of the cells and protein in the lavage fluids from patients with IPF revealed an inflammatory and eosinophilic response and a significant elevation of IgG in the lungs. With corticosteroid therapy, inflammation diminished but eosinophils remained. Lavage fluid from patients with CHP also had eosinophils and elevated levels of IgG. However, in contrast to IPF, lavage fluid from CHP patients contained IgM, fewer inflammatory cells, and a strikingly increased number (38-74%) of lymphocytes. Identification of lavage lymphocytes in CHP showed that T lymphocytes were significantly elevated and B lymphocytes were decreased compared to peripheral blood. These studies suggest nthat the lung in IPF and CHP may function as a relatively independent immune organ, and that analysis of cells and proteins in broncho-alveolar lavage fluid may be of diagnostic, therapeutic, and investigative value in evaluating patients with fibrotic lung disease.

Aged↗
PubMed1977

Mechanism for the inflammatory response in primate lungs. Demonstration and partial characterization of an alveolar macrophage-derived chemotactic factor with preferential activity for polymorphonuclear leukocytes.

Approximately 4 h after an initial bronchoalveolar lavage (BAL) of a primate's lung, an appreciable number of polymorphonuclear leukocytes (PMNs) were noted to accumulate in respiratory fluids when lavage was repeated. Whereas, alveolar macrophages (90%) and lymphocytes (7%) were the principal respiratory cells recovered initially from lavage fluid, later samples contained 45-90% PMNs To explain the observed ingress of PMNs into lung fluids, concentrated BAL fluid was tested for chemoattractant activity. Such fluid obtained 4 and 24 h after an initial lavage contained material that produced directed migration (chemotaxis) for PMNs and mononuclear cells isolated from peripheral blood of normal donors. Gel filtration chromatography of BAL disclosed two peaks of chemotactic activity in the effluent fractions. Material from the column with an estimated molecular weight of 15,000 daltons was chemotactic for both PMNs and mononuclear cells. Because it was susceptible to inactivation with antiserum against the fifth component of complement, resistant to heating, and unaffected by antiserum against C3, this factor was considered analogous to the cleavage product of the fifth component of complement. C5a. In addition chemotactic activity for PMNs only was contained in an effluent peak having a molecular weight of about 5,000 daltons. This material was heat labile but unaffected by antisera to complement components. To locate the possible source of these factors in respiratory fluid, in vitro cultures of alveolar macrophages were established. These cells, whether stimulated by phagocytosis of opsonized bacteria or merely by attachment to a glass surface, produced chemotactic material which had physical characteristics similar to the small molecular weight material in BAL. Moreover, it induced preferential chemotaxis for PMNs. Thus, in primate lungs, at least two chemotactic substances may generate an inflammatory response; one which is a fragment of the complement component C5 and another small molecular weight factor which is released from alveolar macrophages.

Animals↗
PubMed1976

Changes in the composition of canine respiratory cells obtained by bronchial lavage following irradiation or drug immunosuppression.

Canine respiratory cells, obtained by bronchial lavage, and blood leukocytes were monitored to observe cellular changes following acute and chronic immunosuppression. Irradiation (350 R) produced bone marrow suppression and prompt peripheral blood leukopenia, but did not affect recovery of pulmonary alveolar macrophages or lymphocytes for 12 days after. Treatment for 6 weeks with daily methylprednisolone (1 mg/kg) caused a progressive decrease in the number of recoverable respiratory lymphocytes, whereas alternate day methylprednisolone (2 mg/kg) had less effect. Cyclophosphamide in combination with steroids generally augmented the progressive loss of blood and respiratiory lymphocytes. Recovery of alveolar macrophages was not changed appreciably. Thus, the population of lung macrophages, sampled by pulmonary lavage, withstood acute and chronic forms of immunosuppression very well. In contrast, canine lymphocytes seem more susceptible to injury, especially to drug regimens containing steroids.

Animals↗
PubMed1976

Kinetics of immunoglobulin transport into canine bronchial secretions.

Radiolabeled 125I Preparations of canine IgG, IgM, and F(ab')2 fragments of IgG were injected intramuscularly into normal dogs to quantitate the transfer of immunoglobulins from the intravascular space into the lower respiratory tract and to observe the clearance of these proteins from lung secretions. Respiratory fluids were sampled by serial broncho-alveolar lavages during a 3-4 week interval. Only a small portion (0.15%) of the passively administered IgG was recovered in respiratory specimens indicating that minimal transfer of humoral IgG occurs under normal conditions. Alteration of the IgG molecule by removal of the Fc portion almost eliminates its penetration into lung secretions. Furthermore, IgM, which is not a prominent component of normal lung secretions, is not detected in these secretions following passive intramuscular injection.

Animals↗
PubMed1976

Chediak-Higashi syndrome: reversal of increased susceptibility to infection by bone marrow transplantation.

Transplantation of normal bone marrow to mice with the Chediak-Higashi syndrome (CHS) resulted in normal granulopoiesis and a reversal of their increased susceptibility to challenge with intravenous Candida albicans. These findings suggest that (1) the leukocyte defect in CHS can be reversed by marrow transplantation and (2) the mechanism for increased susceptibility to infection in these animals is due to a bone-marrow-derived cellular defect. Because of similarities between murine and human CHS, bone marrow transplantation might be considered as a mode of therapy in selected cases of the human disease.

Animals↗
PubMed1976

Characterization of lymphocytes in bronchial lavage fluid from monkeys.

At least two populations of lymphocytes can be identified in primate lung washings, one forming rosettes with SRBC and another forming rosettes with erythrocyte-antibody-complement complexes. The response to mitogens by cells from lavage fluid is similar to spleen and blood lymphocytes. The distribution of lymphocytes in pulmonary lavage fluid is similar to that found in the peripheral blood. The identity of lymphocyte populations in respiratory fluids has relevance in understanding the immunologic capabilities of the primate respiratory tract.

Animals↗
PubMed1975

Specificity of opsonic antibodies to enhance phagocytosis of Pseudomonas aeruginosa by human alveolar macrophages.

These studies compared the ability of specific secretory IgA (sIgA) and IgG antibodies to promote phagocytosis of viable pseudomonas aeruginosa by human alveolar macrophages. Macrophages were obtained by lung lavage of normal adult smoker and nonsmoker volunteers and were maintained as in vitro cell monolayers. Both immune sIgA and IgG agglutinating antibodies were demonstrated to coat and opsonize viable bacteria, whereas similar nonimmune immunoglobulin preparations did not. When alveolar macrophages were challenged with viable opsonized 14C-labeled Pseudomonas IgG-reacted bacteria were ingested better and killed more readily than sIgA-opsonized organisms. Phagocytic responses were not significantly different between macrophages obtained from smokers and nonsmokers. Although sIgA and IgG antibodies can be found in respiratory secretions and both are undoubtedly important in pulmonary host defense, IgG opsonic antibody was superior in enhancing the uptake of Pseudomonas by in vitro-cultured alveolar macrophages. It may be the more important respiratory antibody for certain bacterial infections.

Adult↗