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Biomedical subjects

D M Strong

Publications and source records attributed to D M Strong.

At least 109 records · Page 6Linked to original sources

Extrinsic allergic alveolitis after Aspergillus fumigatus inhalation. Evidence of a type IV immunologic pathogenesis.

Three weeks after a massive inhalation of mold present on infected oats, a farmer's wife had extrinsic allergic alveolitis. Aspergillus fumigatus was cultured from the moldy oats and from deep bronchial washings obtained at fiberoptic bronchoscopy. Spores and hyphae characteristic of Aspergillus species were demonstrated within granulomas in the pulmonary tissue obtained by transbrochial biopsy. Serum precipitins, delayed (48 hour) cutaneous hypersensitivity and in vitro lymphocyte transformation to A. fumigatus were demonstrated. The findings in this case suggest that a type IV immunologic response and subsequent (lymphocyte-mediated) tissue inflammation may underlie the pathogenesis of this and other forms of hypersensitivity pneumonitis.

Adolescent↗

Selective immunoglobulin M (IgM) deficiency in two immunodeficient adults with recurrent staphylococcal pyoderma.

Two adult men with recurrent pyoderma due to Staphylococcus aureus and a selective deficiency of immunoglobulin M (IgM) antibody synthesis are described. An analysis of each patient's polymorphonuclear leukocyte chemotaxis, phagocytosis and killing of Staph. aureus, serum opsonizaiton of Staph. aureus, and serum and lymphocyte-mediated responses to antigenic stimulation was performed. Family studies revealed a possible autosomal dominant inheritance pattern with heterogenetic expression of various dysgammaglobulinemic states in each patient's first degree relatives. In vivo studies of delayed hypersensitivity and in vitro studies of polymorphonuclear leukocyte and lymphocyte function were normal. A defect in IgM, but not in IgG (immunoglobulin G), antibody synthesis to a number of antigens, and a mild decrease in serum opsonic activity to Staph. aureus correctable by heat inactivated normal human serum were found in each patient. In these patients, the recurrent staphulococcal pyoderma prompted an investigation of host defense mechanisms and revealed low to absent IgM levels and a defect in IgM antibody synthesis.

Adult↗

Competent cellular immunity in allergic rhinitis patients with elevated IgE.

Parameters of cell-mediated immunity (CMI) were studied in 17 allergic rhinitis patients selected for markedly elevated total serum IgE levels (greater than 300 IU/ml) and 14 normal controls. Mean serum IgE levels were 1,421 IU/ml and 101 IU/ml in the allergic and control groups, respectively (p less than 0.001). There were no significant differences between the allergic patients and the normal controls in delayed cutaneous hypersensitivity, in mitogen and antigen lymphocyte transformation in heterologous or autologous plasma, or in percentage of sheep erythrocyte rosettes. The allergic patient group had a significantly higher percentage of sheep erythrocyte-antibody-complement rosettes (p less than 0.05). Markedly elevated total serum IgE levels in allergic rhinitis patients were not associated with any detectable impairment of CMI.

Adult↗

Studies on the antigenicity of bone. I. Freeze-dried and deep-frozen bone allografts in rabbits.

The antigenicity of deep-frozen and freeze-dried cortical and corticocancellous bone allografts placed orthotopically in rabbits was studied using a sensitive microcytotoxicity assay. Target cells were phytohemagglutinin-P-stimulated, 51chromium-labeled peripheral blood lymphocytes from the bone donors (Dutch belted rabbits), and sera or peripheral blood lymphocytes from the graft recipients (New Zealand white rabbits) were used as effectors of cytotoxicity. Fresh allografts and deep-frozen corticocancellous bone evoked detectable humoral and cell-mediated immunity,, whereas freeze-dried cortical bone allografts failed to sensitize the recipients and were the least antigenic of the allografts examined.

Animals↗

Selective inhibition of lymphocyte responsiveness to phytohaemagglutinin in patients with Reiter's syndrome.

The influence of synovial fluid from four patients with Reiter's syndrome on lymphocyte responsiveness was studied. On synovial fluid was found which specifically depressed the responsiveness of lymphocytes from patients with Reiter's syndrome to the non-specific mitogen phytohaemagglutinin (PHA). The ratio of the responsiveness of lymphocytes cultured in the presence of foetal calf serum (FCS), compared to those incubated in the Reiter's synovial fluid, was used as a measure of the depression induced by the Reiter's synovial fluid. The mean ratio for eight normals stimulated with PHA was 0-70 (range 0-35-0-96), while for eight patients with Reiter's syndrome, it was 0-13 (range 0-07-0-19). Similar studies done with concanavalin A (con A) showed no difference between lymphocytes from normals (0-73) or patients with Reiter's syndrome (0-67). Chromatography of the Reiter's synovial fluid on a Sepharose 4-B column resulted in the separation of three major fractions, one of which exhibited the inhibitory activity. When this active fraction was absorbed with Reiter's lymphocytes, a loss of the inhibitory activity of the fraction was seen. A similar absorption with normal lymphocytes had no effect. These studies demonstrate that a factor present in the synovial fluid of a patient with Reiter's syndrome reacted specifically with lymphocytes from patients with Reiter's disease and not with lymphocytes from normals. The interaction of this factor with lymphocytes from patients with Reiter's syndrome inhibited the responsiveness of these lymphocytes to PHA but not to con A.

Adult↗

X-linked B-lymphocyte immune defect in CBA/HN mice. I. Studies of the function and composition of spleen cells.

A study of the composition and functional properties of spleen cells from the immune deficient CBA/HN mice and their F1 progeny is reported. While abnormalities were seen in both the numbers and function of thymus-independent (B) lymphocytes, all studies involving thymus-dependent (T) lymphocytes were normal. The X-linked nature of the immune defect in these mice was therefore attributed to abnormal or absent B lymphocytes. The possible nature of this defect and the similarity of the immune defect in these mice to certain human X-linked immunodeficiency diseases are discussed.

Animals↗

Specificity and immunosuppressive potency of a rabbit antimouse T cell-specific antiserum.

An attempt was made to prepare a specific heterologous rabbit antimouse T cell antiserum (anti-MTLA) by absorbing rabbit antimouse thymocyte globulin (ATG) with spleen cells from BALB/c TXBM mice. Cytotoxicity data showed that whereas ATG was cytotoxic to both T and B cells, anti-MTLA was highly cytotoxic to only T cells. Whereas spleen cells treated with ATG and complement (C) failed to respond in all assays studied, spleen cells treated with anti-MTLA and C: (1) responded to the B cell mitogens but failed to respond to the T cell mitogens; (2) were able to stimulate allogeneic spleen cells but failed to respond to mixed lymphocyte culture (3) failed to act as T killer cells in the CML reaction but retained their ability to kill antibody-coated target cells; and (4) did not cause a graft-versus-host reaction when injected in allogeneic mice and increased their survival significantly. Furthermore, anti-MTLA was just as immunosuppressive in vivo as ATG in its ability to suppress the immune response to sheep red blood cells and prolong skin allograft survival. Anti-MTLA was found to be different in specificities from anti-theta serum by several points: (1) it was cytotoxic for T cells from both theta-C3H and theta-AKR mice; (2) it was highly immunosuppressive in vivo when compared to anti-theta serum; (3) absorption of anti-MTLA with mouse brain did not decrease the immunosuppressive activity; and (4) rabbit antimouse brain antiserum failed to show any immunosuppressive activity. These data indicate that anti-MTLA is a specific antiserum against a unique marker on T cells distinct from the theta marker.

Animals↗

Human T-cell heterogeneity as delineated with a specific human thymus lymphocyte antiserum. In vitro effects on mitogen response mixed leukocyte culture, cell-mediated lymphocytotoxicity, and lymphokine production.

Human peripheral blood lymphocytes (PBL) were evaluated by their responses to phytohemmagglutinin (PHA-P), concanavallin A (con-A), and pokeweed mitogen (PWM), both before and after treatment with an antiserum against human thymic lymphocyte antigens (HTLA) that had been made T-cell-specific by multiple absorptions with immunoglobulin EAC-positive lymphoblast cell lines (B cells). Cells treated with HTLA were examined for their ability to react in a mixed lymphocyte culture (MLC) and to form killer cells in a cell-mediated lymphocytotoxicity (CML) system. Sensitized cells were also examined for their ability to respond to purified protein derivative (PPD) by blastogenesis, migration inhibitory factor release (MIP), and lymphotoxin (LT) production, both before and after treatment with HTLA and complement. The HTLA was in itself highly stimulatory to PBL. However, with the addition of complement and subsequent cell destruction, a marked decrease in its stimulatory response was noted. PBL treated with HTLA and complement exhibited marked inhibition of responsiveness to con-A with little decrease in PHA-P -OR PWM stimulation except at very high concentration of HTLA. MLC reaction was inhibited only when responder cells were treated with HTLA + C'. Treatment of stimulator cells with HTLA + C' did not significantly alter the MLC response. The HTLA + C'-treated cells failed to form killer cells in the CML reaction and inhibited PPD-induced blasto-genesis from PPD-sensitized individuals; however, treatment of sensitized cells with HTLA + C' had little effects on the release of MIF and LT. It is suggested that subpopulations of T-cells carry surface antigens that bind with this specific antisera, and that the con-A-responsive cells, the responder cells in the MLC, and killer T-cells comprise a separate subset from cells responding to PHA-P or PWM, OR THE MIF-and LT-producing cells.

Animals↗

Polymyxin B reactions, IgE antibody, and T-cell deficiency. Immunochemical studies in a patient after bone marrow transplantation.

A patient with aplastic anemia was immunosuppressed with cyclophosphamide and transplanted with allogenic bone marrow. While lacking demonstrable T-cell activity posttransplantation, he developed a generalized macular erythematous eruption and fever, clinically attributed to intranasal polymyxin B. A specific IgE antibody, demonstrated by direct skin testing, Prausnitz-Kustner passive transfer, and indirect passive hemagglutination was temporally related to the reaction. Discontinuation of the drug led to prompt defervescence and resolution of the drug eruption.

Adolescent↗

Immunological responsiveness of frozen-thawed human lymphocytes.

Mononuclear cells (10--20 X 10(6)) obtained from human peripheral blood by a standard Ficoll-Hypaque technique were suspended in RPMI 1640 media at 4 degrees C containing 10% foetal calf serum and 7-5% dimethyl sulphoxide (DMSO). Two-millilitre aliquots were cooled at -1 degree C/min in a Cryoson BV-4 programmed freezing system to -30 degrees C, then -5 degrees C/min to -80 degrees C and stored in liquid nitrogen vapor. On the day of testing, cell suspensions were thawed rapidly in a 37 degree C water bath. DMSO was diluted slowly out of the sample and cells resuspended in fresh RPMI 1640. It was found that frozen stored human lymphocytes (FSHL) demonstrated all the characteristics of fresh unfrozen cells. These included their ability to form spontaneous rosettes with sheep erythrocytes ('E' rosettes) and sheep erythrocyte--antibody--complement rosettes ('EAC' rosettes). The presence of surface immunoglobulins and Fc receptors were shown by membrane immunofluorescence to be comparable. In addition, the results show that FSHL respond to mitogens, specific antigens; act as both stimulators and responders in the mixed lymphocyte culture reaction; and exhibit cell-mediated lymphocytotoxicity following in vitro sensitization, or against antibody-coated target cells.

Adult↗

The immune response to a synthetic amino acid terpolymer in man: relationship to HL-A type.

The immune response to the synthetic amino acid terpolymer (L-glutamic acid-55 L-lysine-33 L-tyrosine15)n (GLT) was studied in normal human volunteers. Delayed skin test reactivity to this antigen was seen in 34 of 61 subjects immunized with 150 mug of GLT. No antibody to GLT was detected in these responding individuals. There was a close correlation between the in vivo skin reactivity of volunteers to GLT and the ability of their lymphocytes to produce migration inhibitory factor (MIF) in response to GLT in vitro. However, a similar correlation was not seen when the in vitro proliferative response of lymphocytes to GLT, as measured by [methyl-3H] thymidine ([3H] T dR) incorporation, was assayed. HL-A typing of volunteers was studied to determine if responsiveness to GLT was correlated to HL-A type. No statistical association was seen after correction was made for the number of individual HL-A antigens.

Adolescent↗

Demonstration of a blocking factor in the plasma and spinal fluid of patients with subacute sclerosing panencephalitis. I. Partial characterization.

Conflicting reports on the immune responsiveness of patients with subacute sclerosing panencephalitis (SSPE) have been reported. This report shows that the leucocytes from four SSPE patients exhibited strong sensitivity to both measles and SSPE virus preparations as measured by the macrophage migration inhibition test, mixed lymphocyte virus infected cell culture test, and the lymphotoxin assay. Earlier suggestions that a factor may be operating to suppress cellular reactivity are confirmed by the demonstration that the response of lymphocytes from SSPE patients could be blocked by the addition of SSPE spinal fluid or plasma. It was determined that the blocking factor was stable at -20 degrees C, heat labile at 56 degrees C for 30 minutes, trypsin and neuraminadase sensitive, and had a mol wt greater than 150,000 as determined by Sephadex G-200 gel chromatography. The blocking factor appeared to be specific for SSPE virus and did not block the response of lymphocytes to nonspecific mitogenic agents and other viral and bacterial agents.

Antibodies↗