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Biomedical subjects

F C Grumet

Publications and source records attributed to F C Grumet.

At least 127 records · Page 7Linked to original sources

Histocompatibility (HL-A) antigens in psoriasis.

In 101 white psoriatic patients, two histocompatibility (HL-A) specificities were significantly altered from expected values. The levels of W16 and W17 were found to be substantially increased, suggesting that persons with these antigens are at increased risk of having psoriasis. Clinically distinct patient groups were also observed. Antigens W16 or W17 or both were more prevalent in psoriatic patients who had extensive disease involvement, and patients with W17 antigen had an earlier age of onset as compared to patients with W16 antigen. In one family in this study, a linkage between psoriasis and a specific HL-A haplotype was also observed, further supporting the concept that the HL-A system may serve as a marker for genes affecting specific disease susceptibility.

Adolescent↗

HL-A antigens in Japanese Patients with Graves' disease.

A group of Japanese were investigated for evidence of an association between Graves' disease and HL-A. Forty-four patients with the disease and 83 normal, unrelated random Japanese and Japanese-American controls were selected for study. The frequency of the W5 antigen among patients (57%) was significantly (P less than .0001) greater than among controls (20%). Of the 34 patients with abnormally elevated serum levels of anti-(thyroid) microsomal (anti-M) auto-antibodies, 56% had the W5 antigen. In contrast, of 48 control individuals tested for anti-M, only seven were seropositive and none (0%) of the seven had the W5 antigen. As expected the HL-A8 antigen was absent from this non-Caucasian population. These data demonstrate that the W5 antigen in Japanese, analogous to the HL-A8 antigen in Caucasians, is associated with Graves' disease but not with anti-M seropositivity in controls. The occurrence of different HL-A antigens in association with the same disease in different ethnic groups requires that the use of a major histocompatibility system antigen as a disease susceptibility marker must be confirmed for each ethnic group under study.

Antilymphocyte Serum↗

Characterization of erythrocyte membrane-associated enzymes (glyceraldehyde-3-phosphate dehydrogenase and phosphoglyceric kinase).

The purpose of our study was to determine why several of the glycolytic enzymes of the erythrocyte have the propensity for adhering to erythrocyte membranes while others do not. Two of these membrane-associated enzymes, glyceraldehyde phosphate dehydrogenase (GAPD) and phosphoglyceric kinase (PGK), have been shown to have controlling functions on intra-erythrocytic glycolysis and sodium-potassium transport. In order to test the hypothesis that the membrane-associated fraction of these enzymes consisted of isozymes with increased capacity to become membrane associated, the enzymes from cytosol or membrane sources were partially purified and characterized. Determination of molecular weight by gel filtration chromatography, measurement of certain kinetic parameters, and the curves relating to pH optimal activity indicated that there were no measurable differences between membrane and cytosol PGK and membrane and cytosol GAPD. It was possible to raise inhibitory antibodies to GAPD in certain species of mice, and these antibodies did not distinguish between GAPD isolated from either membrane or cytosol sources. GAPD was firmly bound to membranes and the membrane-associated fraction counted for approximately 60 per cent of total erythrocytic enzyme. Membrane-associated PGK was only loosely adherent, and accounted for only 1 per cent of the total erythrocytic enzyme. The reasons for membrane association have yet to be determined, but these inward facing membrane-associated enzymes appear to function by carrying the organization of the membrane into the cell interior.

Animals↗

Genetic control of the immune response. The effect of graft-versus-host reaction on the antibody response to poly-L(Tyr, Glu)-poly-D,L-Ala--poly-L-Lys in nonresponder mice.

The transfer of parental (H-2(k/k)) nonresponder lymphoid cells into heterozygous (H-2(k/q)) nonresponder recipients at the time of primary challenge with aqueous poly-L(Tyr,Glu)-poly-D,L-Ala-poly-L-Lys [(T,G)-A--L] elicited the production of both IgM and IgG anti-(T,G)-A--L antibody. Normally, the production of IgG anti-(T,G)-A--L antibody is restricted to strains possessing the responder Ir-1 allele. The timing and intensity of the graft-versus-host (GVH) reaction required for this effect were found to be critical. Injection of H-2(k/k) cells into H-2(k/q) recipients 1 wk before antigen challenge did not elicit IgG anti-(T,G)-A--L antibody production, and markedly suppressed IgM anti-(T,G)-A--L antibody production. The transfer of alloimmune (H-2(q)-primed) H-2(k/k) cells at the time of antigen challenge was also associated with no IgG and little IgM anti-(T,G)-A--L antibody production. These data are consistent with the model that nonresponder thymus-derived lymphocytes (T cells) activated in a GVH reaction can substitute for (T,G)-A--L-reactive T cells to induce a shift from IgM to IgG anti-(T,G)-A--L antibody production.

Amino Acid Sequence↗

Genetic control of the immune response. A selective defect in immunologic (IgG) memory in nonresponder mice.

The kinetics of antibody formation after immunization with the synthetic polypeptide poly-L(Tyr, Glu)-poly-D, L-Ala--poly-L-Lys [(T, G)-A--L] in aqueous solution were studied in genetically high (H-2(b)) and low (H-2(k)) responder strains of mice. During the 1st wk after immunization both strains developed brisk primary responses consisting of IgM antibody. With subsequent antigen challenge, only the high responder mice showed immunological memory, producing high titers of IgG antibody. In contrast, the low responder mice continued to make a persistent low level of IgM antibody and appeared unreactive to secondary or tertiary antigen challenge. These data are consistent with the hypothesis that the immune response-1 gene [controlling response to (T, G)-A--L] exerts its effect on the immune response at the time of switchover from IgM to IgG antibody production.

Amino Acid Sequence↗

Genetic control of the immune response. The effect of thymectomy on the primary and secondary antibody response of mice to poly-L(tyr, glu)-poly-D, L-ala--poly-L-lys.

The effect of thymectomy on the genetically controlled murine immune response-1 (Ir-1) to the synthetic polypeptide poly-L(Tyr, Glu)-poly-D, L-Ala--poly-L-Lys [(T, G)-A--L] was studied with both aqueous and adjuvant immunization regimens. Adult thymectomy (combined with irradiation and bone marrow transfusion) did not affect the aqueous antigen-induced (IgM) primary response of either high or low responder mice, but did ablate the (IgG) secondary or tertiary response, a response which is restricted to the high responder strains. Adult thymectomy also blocked the normal high response to (T,G)-A--L in Freund's adjuvant in high responder mice and the high response to methylated bovine serum albumin (MBSA)-(T,G)-A--L in low responder mice. Neonatal thymectomy was also effective in blocking the response to (T, G)-A--L in Freund's adjuvant in high responder mice. These data are consistent with the concept that the Ir-1 gene effect is mediated via thymus cell interaction with antigen and with "B"-cells during the time of induction of IgG antibody formation.

Adjuvants, Immunologic↗