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M Graves

Publications and source records attributed to M Graves.

44 records · Page 3Linked to original sources
PubMed1975

Cell interactions between histoincompatible T and B lymphocytes. VII. Cooperative responses between lymphocytes are controlled by genes in the I region of the H-2 complex.

The results of this study provide compelling evidence for the existence of the gene or genes controlling optimal T-B-cell cooperative interactions in the designated I region of the H-2 gene complex. Previously, we have speculated that the relevant gene(s) involved may well be located in this region based on several observations from our earlier work in this area (3, 5, 6). Thus, in the preceding paper, we showed that T and B cells from B10.BR and A strain mice developed effective cooperative interactions in vitro to DNP-KLH in a system identical to the one reported herein. Since these mice differ for genes in the S and D regions of H-2 but are identical for K and I region genes, we were able to localize the critical genes to the K-end of H-2.

Animals↗
PubMed1975

Cell interactions between histoincompatible T and B lymphocytes. VIII. In vivo cooperative responses between lymphocytes are controlled by genes in the K-end of the H-2 complex.

The genetic restrictions for successful carrier-primed T cell and hapten-primed B cell cooperative interactions were established in a totally in vivo double adoptive transfer system. In complementation experiments, we have demonstrated that genes localized in the K-end of the H-2 complex control successful T-B cell cooperative interactions. Thus, DBA/2 KLH-primed T cells cooperated with (C3H times C3H.OH)F1 and (C3H times C3H.OL)F1 DNP-primed B cells to make a secondary response to DNP-KLH, but not with (C3H times C3H.A)F1 DNP-PRImed cells. The presence of foreign histocompatibility determinants on the F1 B cells did not prevent successful physiologic cell cooperation provided the T and B cells shared common cell interaction genes coded for in the K-end of the H-2 complex.

Aminocaproates↗
PubMed1973

Purification of Hodgkin's disease tumor-associated antigens.

Two antigens that exist in high frequency in tumor tissues of patients with Hodgkin's disease have been obtained in relatively concentrated form. Extracts of Hodgkin's spleen tumor tissue, when subjected to chromatography on Sephadex G-200, separate into three major protein peaks of which only the first (peak I) possesses the predominant antigenic activities associated with the disease. Antigenic analysis performed with hyperimmune rabbit antisera obtained after repeated immunizations with peak I proteins demonstrated that this fraction contained both F and S antigens associated with Hodgkin's disease and small contaminant amounts of an antigen associated with normal lymphocytes. The tissue distribution patterns of the Hodgkin's disease tumor-associated antigens suggest that they both originate in lymphoid tissues and that the F antigen may represent a product of reactive lymphocytes while the S antigen may be a dedifferentiation antigen expressed in very immature lymphocytes.

Animals↗
PubMedDate not supplied

Rational design of a potent, long-lasting form of interferon: a 40 kDa branched polyethylene glycol-conjugated interferon alpha-2a for the treatment of hepatitis C.

A potent, long-lasting form of interferon alpha-2a mono-pegylated with a 40 kilodalton branched poly(ethylene glycol) was designed, synthesized, and characterized. Mono-pegylated interferon alpha-2a was comprised of four major positional isomers involving Lys31, Lys121, Lys131, and Lys134 of interferon. The in vitro anti-viral activity of pegylated interferon alpha-2a was found to be only 7% of the original activity. In contrast, the in vivo antitumor activity was severalfold enhanced compared to interferon alpha-2a. Pegylated interferon alpha-2a showed no immunogenicity in mice. After subcutaneous injection of pegylated interferon alpha-2a, a 70-fold increase in serum half-life and a 50-fold increase in mean plasma residence time concomitant with sustained serum concentrations were observed relative to interferon alpha-2a. These preclinical results suggest a significantly enhanced human pharmacological profile for pegylated interferon alpha-2a. Results of Phase II/III hepatitis C clinical trials in humans confirmed the superior efficacy of pegylated interferon alpha-2a compared to unmodified interferon alpha-2a.

Animals↗
PubMedDate not supplied

S-adenosyl methionine: A connection between nutritional and genetic risk factors for neurodegeneration in Alzheimer's disease.

Clinical manifestation of Alzheimer's disease may depend upon interaction among its risk factors. Apolipoprotein E-deficient mice undergo oxidative damage and cognitive impairment when deprived of folate. We demonstrate herein that these mice were depleted in the methyl donor S-adenosyl methionine (SAM), which inhibited glutathione S-transferase, since this enzyme requires methylation of oxidative species prior to glutathione-dependent reduction. Dietary supplementation with SAM alleviated neuropathology. Since SAM deficiency promotes presenilin-1 overexpression, which increases gamma-secretase expression and Abeta generation, these findings directly link nutritional deficiency and genetic risk factors, and support supplementation with SAM for Alzheimer's therapy.

Adenosine↗