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Biomedical subjects

P R McMaster

Publications and source records attributed to P R McMaster.

At least 19 recordsLinked to original sources
PubMed1987

Presence of retinal autoantigen in normal mice: absence in strains with retinal degeneration.

We examined the eyes of four strains of mice to determine if some or all contained an antigen which might cross-react with an antigen of guinea pig retina. To do this, we prepared guinea-pig antibody to guinea-pig retinal extract by immunizing Hartley guinea pigs with guinea-pig retinal extract in two different adjuvants. The retinal tissue of Balb/c and C57B1/6J mice stained well when we used the guinea-pig antibody to guinea-pig retinal extract. In contrast, the eyes of a subline, i.e., C57B1/6J-rd with retinal degeneration, did not stain. Likewise, the eyes of C3H/HeJ and SJL mice with abnormal retinas did not stain. The latter two strains are known to have retinal degeneration. The control studies were negative. This study shows that normal murine eyes have at least one antigen which cross-reacts with a guinea-pig retinal antigen. It also shows abnormal mouse retinas lack this antigen.

Animals↗
PubMed1986

Induction of autoimmune diseases with adjuvants: separation of delayed hypersensitivity and antibody formation from diseases in experimental thyroiditis and aspermatogenesis with Legionella adjuvant.

The induction of autoimmune diseases in animals was studied with Legionella and mycobacteria as adjuvants, emulsified in oil with antigen extracts of thyroid, testis, spinal cord, and peripheral nerve. Both adjuvants were equally effective in inducing delayed hypersensitivity and humoral antibody to the tissue antigens. The Legionella adjuvant, however, induced little or no thyroiditis and aspermatogenesis, whereas the mycobacterial adjuvant induced thyroiditis and aspermatogenesis. Both adjuvants caused allergic encephalomyelitis and peripheral neuritis. The results indicated that delayed hypersensitivity by itself may not be sufficient to cause thyroiditis and aspermatogenesis. Legionella adjuvant apparently lacked the ability to induce certain immune factor(s) which caused the disease in experimental thyroiditis and aspermatogenesis. The differential properties of Legionella adjuvant and mycobacterial adjuvant in inducing immunity to autoantigens could provide a useful means to study the pathogenic and immunoregulatory mechanisms of some experimental autoimmune diseases.

Adjuvants, Immunologic↗
PubMed1985

Prevention of autoimmune uveitis by competitive immunization with bovine gamma globulin.

The effect of antigenic competition on the development of autoallergic experimental uveitis and autoallergy to ocular antigens was studied. Strain 13 guinea pigs were immunized with adjuvants containing either National Institutes of Health strain retina-uvea extract or retina-uvea extract plus bovine gamma globulin (BGG). They were later reimmunized with ocular extract and BGG or ocular extract alone, in adjuvant. They were observed weekly by slit-lamp examination. At the end of the study, they were skin tested using strain 13 retina-uvea extract. The eyes of certain groups were examined histologically. Immunization and reimmunization with ocular extract produced uveitis. The addition of BGG to the initial immunization prevented the development of uveitis even after reimmunization with ocular extract alone. It did not, however, necessarily prevent the development of delayed type skin sensitivity to retina-uveal extract.

Animals↗
PubMed1984

Adverse reactions to protamine sulfate following cardiac surgery.

We report four patients who developed severe adverse reactions to protamine sulfate following cardiac surgery. Two types of reactions were seen. First, an immediate anaphylaxis which is a complement-dependent IgG antibody-mediated reaction. In the literature, 80% of patients who had similar reactions have had previous exposure to protamine. All patients adequately tested had positive skin tests and there is 6% mortality. The second reaction to protamine during cardiac surgery is characterized by delayed onset and profound vascular damage presenting as noncardiogenic pulmonary edema or total vascular collapse with prolonged hypotension and anasarca. These patients have negative skin tests and in our studies, no evidence of antibody mediated reaction, suggesting some other mechanisms may play a part. The mortality is high (30% of patients reported) and survivors have significant morbidity.

Aged↗
PubMed1984

Comparative adjuvant activities of Legionella pneumophila and Mycobacterium tuberculosis.

Adjuvant activity of heat-killed Legionella pneumophila was demonstrated and compared with that of inactivated Mycobacterium tuberculosis H37Rv. The two species of bacteria were suspended separately in oil and Arlacel A. Bovine serum albumin (BSA) in saline was then emulsified within the respective adjuvants and injected intradermally into guinea pigs. Antibodies to the BSA antigen in the sera of the animals were quantitated with the kinetic-dependent enzyme-linked immunosorbent assay (k-Elisa). Guinea pigs immunized with BSA in adjuvant with killed L. pneumophila produced high titers of anti-BSA antibody, which, on the average, were nearly as high as in those immunized with BSA in complete Freund's adjuvant with M. tuberculosis H37Rv, and which were much greater than in others immunized with incomplete adjuvant, lacking bacteria. Moreover, with a polypeptide hapten, the L. pneumophila evoked as much or more antibody in rabbits as the mycobacterium adjuvant. The effect of the legionella adjuvant upon the cellular immune response was examined using skin tests. For this purpose guinea pigs were immunized with picryl-guinea pig albumin in these adjuvants. 6 weeks later, they were skin-tested with that antigen. They showed reactions which appeared to have immediate as well as delayed components when examined grossly and histologically. Others, immunized with incomplete adjuvant, did not exhibit delayed reactions. Accordingly, heat-killed L. pneumophila acts as a potent adjuvant. Under the circumstances of these experiments, it was as effective as heat-killed M. tuberculosis.

Adjuvants, Immunologic↗
PubMed1979

Studies on the pathogenesis of experimental autoimmune renal tubulointerstitial disease in guinea pigs. VI. Induction of renal lesions by active or passive immunization of strain 2 guinea pigs.

It has been reported that strain 2 guinea pigs do not develop experimental autoimmune renal tubulointerstitial disease (RTD) by active or passive immunization. Under our experimental conditions strain 2 guinea pigs are susceptible to the induction of RTD. Typical moderate to severe renal lesions were seen 22 days after immunization with rabbit tubular basement membrane in complete Freund's adjuvant. Most Albany strain guinea pigs had severe RTD. Susceptibility to induction of RTD by passive transfer of antitubular basement membrane autoantibodies was studied in Albany (A) and strain 2 (2) guinea pigs, as well as in A leads to A, A leads to 2, and 2 leads to A radiation chimeras. Only some strain 2 guinea pigs had mild to severe renal lesions by day 9, but by day 19 all had typical histologic renal abnormalities. Albany guinea pigs already had moderate to severe RTD by days 9-10. Strain 2 differed from Albany recipients by a noticeable delay in the onset of lesions. Bone marrow transplants between Albany and strain 2 did not affect these susceptibility differences. A leads to 2 recipients responded like strain 2, and 2 leads to A like Albany. This indicates that the delay of onset of RTD in strain 2 is not a defect in the bone marrow-derived inflammatory cells.

Animals↗
PubMed1978

Evaluation of a dispensing instrument (Dynatech MIC-2000) for preparing microtiter antibiotic plates and testing their potency during storage.

The MIC-2000 96-channel dispenser was evaluated for accuracy and repeatability of dispensing 50-mul volumes of water. It was found to perform within the manufacturer's specifications for accuracy of +/-5%, but not within the limits for repeatability of +/-1%. Overall, instrument performance was found to be satisfactory for the antimicrobial susceptibility testing technique which has been implemented in this laboratory. A method is suggested for simple evaluation of the volumes dispensed. A variety of antibiotics may be stored in Trypticase soy broth in Microtiter plates without loss of potency for periods of at least 2 weeks at -20 degrees C and 4 months at -70 degrees C.

Anti-Bacterial Agents↗
PubMed1977

Hapten-specific delayed hypersensitivity to epsilon-2,4-dinitrophenyl-L-lysine-Ficoll in guinea pigs immunized with 2,4-dinitrophenyl-keyhole limpet hemocyanin.

After active immunization with 2,4-dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH), 2,4-dinitropheynl-L-lysine (DNPL)-Ficoll may elicit indurated, erythematous skin reactions lasting 24-72 h. Histological sections of these reactions, examined by microscope techniques, showed they contained polymorphonuclear leukocytes and perivascularly situated lymphocytes and macrophages, but had very few basophils. Consequently, the reaction was interpreted as having an immediate component and a component typical of delayed hypersensitivity; this indicated that the delayed reaction could be specific for the DNP hapten. Although this delayed type of skin reaction was not transferred to recipients with anti-DNP-KLH serum, one pool of that serum did sensitize guinea pigs so that they could respond with a different skin reaction after challenge with DNPL-Ficoll. This reaction was soft, pale pink, and lasted for 24 h. Histologically, it contained only a few polymorphonuclear leukocytes. It differed from the delayed reaction in actively immunized animals in that it lacked induration, and was devoid of lymphocytes and macrophages.

Animals↗
PubMed1977

Hapten-specific leukocyte migration inhibition. I. Inhibition of cells from animals immunized with DNP-KLH by epsilon-DNP-L-lysine Ficoll.

Guiena pigs were immunized with dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH) or with hemocyanin in complete Freud's adjevant. The migration of oil-induced peritoneal exudate cells was measured in the presence and absence of epsilon-dinitrophenyl-lysine-tyrosinyl Ficoll (DNPL-F). When the cells came from animals immunized with DNP-KLH their migration was inhibited by DNPL-F. Control cells from animals immunized with KLH or not immunized migrated normally in the presence of DNPL-F.

Animals↗
PubMed1977

Rhodopsin and blindness.

Systemic immunization with purified homologous rhodopsin from retinal outer segments induced blindness in primates (Macaca mulatta). Inflammation and characteristic retinal changes were the earliest clinical signs of the disease. Perivasculitis, subretinal exudations and bullous detachments of the retina were progressive and unrelenting pathological processes leading to rapid and irreversible visual deterioration. Electroretinographic responses (ERG) at this stage of the disorder became abolished. Antibodies and delayed hypersensitivity to rhodopsin were demonstrated only in the experimental diseased animals. Homologous visual purple appears to be organ and immunopathologically specific. Histological confirmation of these findings showed a pathological spectrum of destructive alterations confirmed specifically to the outer segments of the entire retina. The pathologic reaction was supported by a distinct and pronounced granulomatous inflammatory response.

Animals↗
PubMed1976

The propensity of different strains of guinea pigs to develop experimental autoimmune uveitis.

We compared the propensity of several strains of guinea pigs to develop autoimmune experimental uveitis and autoimmunity following immunization with retinal-uveal antigens in complete Freund's adjuvant. The Hartley and NIH strains developed the disease more frequently and more severely than the strain 13 animals. The strain 2 guinea pigs did not develop the disease at all. In addition, the strain 2 did not make as much delayed hypersensitivity or as much antibody as the Hartley and NIH strain animals. NIH guinea pigs lacking the fourth component of complement made as much disease as those with that enzyme.

Animals↗
PubMed1976

Experimental autoimmune thyroiditis in the guinea pig: characterization of infiltrating lymphocyte populations.

Experimental autoimmune thyroiditis was induced in out-bred guinea pigs by isoimmunization with thyroid extract in complete Freund's adjuvant. A digestion procedure using collagenase and deoxyribonuclease was used to make viable single-cell suspensions of pooled thyroid glands from groups of animals with advanced degrees of thyroiditis. Thymus-derived or T lymphocytes, identified by their capacity to form E rosettes with rabbit erythrocytes, were found to be the predominant (75%) infiltrating lymphocyte; bone marrow-derived or B cells consitituted most of the remainder. The infiltrates of inbred animals with thyroiditis were demonstrated to contain cells capable of mediating antibody-dependent lymphoid cell-mediated cytotoxicity.

Animals↗
PubMed1975

Homologous retinal outer segment immunization in primates. A clinical and histopathological study.

Immune intraocular inflammation was induced in primates with homologous retinal outer segments. Perivascular retinitis, uveitis, and edema of the optic nerve head were the prominent acute clinical features. Acute and chronic inflammation was seen in the central and peripheral retinal vessels and granulomatous infiltration was present in the choroid of the uvea. Selective degeneration of the outer segments of the photoreceptor cells of the retina with sparing of the inner segments and of the adjacent pigment epithelium was confirmed by light and electron microscopy. This study strongly suggests that photoreceptor outer segments are highly and specifically immunogenic. The inciting antigen has yet to be identified. Implication of rhodopsin will have to await further studies since it exists as the essential protein in the outer segment.

Animals↗
PubMed1975

Prevention of experimental allergic uveitis. Treatment and methotrexate.

These experiments were undertaken to determine if methotrexate therapy, initiated after immunization, could prevent the development of experimental allergic uveitis. Strain 13 guinea pigs were immunized with Strain 13 guinea pig retina-uvea extract that had been emulsified in Freund complete adjuvant. Some were treated with methotrexate twice a week until the 21st day. Each week, all of their eyes were examined with a slit-lamp. At the end of the study, some were skin tested, and the sera of selected animals were tested by immunodiffusion for antibody. The eyes of certain groups were examined histologically. Results show methotrexate prevented the development of this type of uveitis, even when therapy was initiated seven days after immunization. The disease did not appear after therapy was stopped. Methotrexate also inhibited the development of skin sensitivity and antibody to retina-uvea antigen.

Animals↗
PubMed1975

DNP-Lys-ficoll: a T-independent antigen which elicits both IgM and IgG anti-DNP antibody-secreting cells.

The 2,4-dinitrophenyl-lysyl derivative of Ficoll (DNP-Lys-Ficoll) was prepared and examined for immunogenicity. This antigen elicited large numbers of DNP-specific plaque-forming cells (PFC) of the IgM and IgG2 class in the spleens of C57BL/6 mice. Similar responses were observed in congenitally athymic (nu/nu) mice and in their littermates indicating that DNP-Lys-Ficoll is a T-independent antigen. The responses of nu/nu mice included a large number of IgG2 DNP-specific PFC, indicating that IgG responses can be initiated in the absence of mature thymus-dependent (T) lymphocytes. Cell transfer studies confirmed the T independence of the response and indicated that priming with DNP-Lys-Ficoll induces only a very meager degree of memory. Because they can be obtained in large quantities and in relatively pure form, DNP-Lys-Ficoll and other hapten conjugates of Ficoll should prove most valuable in the delineation of the mode of activation of precursors of antibody-secreting cells by T-independent antigens.

Animals↗