PubMed Health⌕ Search

Biomedical subjects

R J Graff

Publications and source records attributed to R J Graff.

At least 19 recordsLinked to original sources
PubMed1994

Continued mapping of chromosome 2 genes.

This report describes our continued efforts to elucidate the genetic fine structure of the central portion of the mouse chromosome (Chr) 2. Mice from our panel of 28 Chr 2 congenic strains were tested: 1) for the presence of the antigens which stimulate Chr 2-reactive lymphocyte clones in mixed lymphocyte reaction (MLR); 2) for the antigens of histocompatibility (H) genes H-42a and H-45a as determined by allograft rejection; and 3) for their ability to respond to the H-Y antigen in a cell-mediated lysis assay. The results obtained in this study have allowed additional mapping of immunologically involved Chr 2 genes. The gene encoding the antigen which stimulates lymphocyte clone 1C11 can be considered wholly different from other Chr2 H genes on the basis of chromosomal recombination. We have assigned the symbol H-48 to this gene. The following gene order has been established: [H-3, B2m, pa], we, [H-42, H-48,] H-45, IR-H-Y, Hd-1, un, H-13, Aw. The order of the bracketed genes is not known. H-44 maps centromeric to IR-H-Y. The genes encoding the antigens that stimulate lymphocyte clones 2G7, 2C10, 1F6, 1B10, and 1H10 map centromeric to H-45.

Animals↗
PubMed1991

Additional mapping of mouse chromosome 2 genes.

The purpose of this work was to elucidate the genetic fine structure of the central portion of mouse chromosome (Chr) 2. Seven Chr 2 congenic mouse strains [B10.PA(L)-pa we un at, B10.PA(L)-pa Aw, B10.PA(L)-we un at, B10.PA(J)-pa a, B10.FS-we Aw, B10.C-we Aw, and B10.YBR-a] were produced. Breeding studies were carried out using strains B10.PA(L)-pa we un at and B10.LP-H-13b to accurately determine the recombination frequencies between marker genes pa and we (1.9% +/- 0.3), we and un (8.8% +/- 0.5), and un and at (4.5% +/- 0.4) of strain B10.PA(L)-pa we un at. These strains and other Chr 2 congenic strains were typed for immunologically defined loci using monoclonal antibody (mAb) C23 reactive with the gene product of B2mb T-lymphocyte clone C1 reactive with the gene product of H-3a and H-3c, and lymphocyte clone H1.8 reactive with the gene product of Hd-1a. B2m and H-3 typing located a recombinational event separating [pa B2m H-3] from we (the order of bracketed genes is not known). Hd-1 typing indicated that Hd-1 maps distal to [H-42, H-44] and proximal to un. The gene order [pa, B2m, H-3], we, [H-42, H-45], Hd-1, un, H-13, at, with H-44 mapping centromeric to Hd-1, is indicated by the data.

Animals↗
PubMed1988

Time-response studies of the cellular immune response to cell membrane antigens.

It was the objective of these experiments to study the time-related changes in the responsiveness of the cellular elements of the immune system following contact with single non-H-2 or multiple H-2 histocompatibility antigens. The reactivity of spleen cells from mice that received injections of spleen cells bearing H-1c, H-3c, H-13a, or H-2b cell membrane alloantigens was characterized at intervals following antigen contact. Spleen cells taken from mice not receiving injections showed no in vitro proliferative or cytolytic responsiveness to cells bearing individual non-H-2 antigens; after in vivo antigen contact with single non-H-2 antigens there was an interval of specific cellular unresponsiveness followed by alternating periods of responsiveness and unresponsiveness. The duration of the unresponsiveness immediately following injection correlated with the strength of the injected antigen--specifically, the stronger the antigen, the shorter the period of unresponsiveness. The data indicate fluctuation in the level of helper T lymphocyte activity, as well as cytotoxic T lymphocyte activity. In contrast, in vitro responsiveness elicited by H-2b antigens with and without prior in vivo antigen contact was of a similar magnitude, and both persisted at a relatively constant level. Suppressor mechanisms were not studied. Of particular interest was the observation that in vivo contact with non-H-2 antigens resulted in suppression of spleen cell production of IL-2 in response to lectin stimulation and fluctuation in the magnitude of the primary response of cytotoxic T lymphocytes to H-2 antigens.

Animals↗
PubMed1987

Recognition of the beta-2 microglobulin-B molecule by a CTL clone.

In this report we offer evidence that the beta-2 microglobulin-B (beta 2M-B) molecule is recognized by a cytotoxic T lymphocyte (CTL). Production of GA5, a CTL clone reactive against a membrane antigen with the same strain distribution pattern as beta 2M-B, is described. This clone lysed syngeneic target cells in which native beta 2M-A molecules had been exchanged with beta 2M-B molecules by incubating the cells in serum from beta 2M-B-positive mouse strains. Conversely, the CTL clone GA5 failed to lyse its specific target when beta 2M-B molecules had been exchanged with beta 2M-A molecules by incubating the cells in serum from beta 2M-A-positive, beta 2M-B-negative mouse strains. Strain combinations were chosen so as to limit reactivity to beta 2M and to preclude reactivity to H-3 antigens, thus indicating CTL clone GA5 to be reacting specifically with beta 2M-B.

Animals↗
PubMed1985

CTL and serologically defined antigens of B2m,H-3 region.

The antigens of the B2m,H-3 region of 13 chromosome 2 congenic strains and seven inbred strains have been studied by using CML and serologic techniques. Nine patterns of cross-reactivity have been defined by CML assays. These results are in agreement with an extend previously described cross-reactivity studies. The reactivities of three monoclonal antibodies previously thought to be reacting with B2M-B are shown to differ: Ly-m11 and J-5 react with cells of strain B10-pa,at and clone 23 does not. Two H-3 region loci are hypothesized on the basis of CML and serologic activity: B2m and H-3. The CTL responses to the B2M antigens are H-2K restricted; the CTL responses to H-3 antigens are H-2D restricted. The restriction of the response to the H-3 antigen requires effector-target identity of the H-2D molecule but not the B2M molecule of the class I antigen. These loci have been separated by recombination from H-42 in the production of the congenic strain B10.FS-a. A gene order of B2m, H-3, H-42 is suggested.

Animals↗
PubMed1985

Allograft rejection-defined antigens of the B2m,H-3 region.

In this report we delineate the production and histocompatibility characteristics of two new B2m, H-3 region congenic strains, B10.SM-a and B10.FS-a, and further characterize previously described strains. Strains C57BL/10 and B10-we are shown to be histocompatible by the exchange of skin grafts, as are strains B10.UW-we,un at, B10.UW we un a, B10.UW-we + a, B10.UW-+ + a and B10.LP-a. (The latter group will be called B10-H-3b when referred to collectively). C57BL/10, B10-H-3b, B10.C-a, B10.KR-a, B10-pa at, B10.SM-a, and B10.FS-a are shown to be histoincompatible by the rejection of exchanged skin grafts, and histoincompatibility between these strains has been localized to the B2m, H-3 region. The histoincompatibility between C57BL/10 and B10.FS-a is of particular significance because of the identity of these strains at the B2m, H-3 region loci B2m and H-3. Thus the B2m, H-3 region histoincompatibility herein described defines a new locus, which we have called H-42, the a allele being assigned to C57BL/10 and the b allele to B10.FS-a. By using cross-immunization techniques, four allograft rejection-defined reactivity patterns (ADR) have been defined that show concordant strain distribution patterns with the CTL-defined reactivity patterns described elsewhere. On the basis of data presented in this report indicating C57BL/10 and B10.FS-a to differ by a histocompatibility gene in the B2m, H-3 region, and data presented by Kurtz et al. elsewhere indicating C57BL/10 and B10.FS-a to possess the same alleles at the B2m and H-3 loci, the presence of at least three B2m, H-3 region loci-defining cell membrane antigens is established.

Animals↗
PubMed1981

Genetic control of cross-reactive cytotoxic T-lymphocyte responses to a BALB/c tumor.

Using a segregation analysis we have determined that the cross-reactive response to the DBA/2 tumor P815 by CTL from BALB/c mice immunized with a BALB/c plasmacytoma (MOPC-167) is controlled by a single gene. The gene responsible is closely linked to the dilute coat color locus on chromosome 9. In contrast, the cross-reactive response to the DBA/2 tumor L5178Y by DBA/2 anti-MOPC-167 CTL appears to be controlled by two or more genes.

Animals↗
PubMed1979

Time-dose-response studies on cellular immunity.

The time-dose responses to several murine histocompatibility antigens were studied using lymphocytes as an antigen source for immunization and the speed of rejection of skin grafts as an assay of the level of immune responsiveness. It was observed that the weaker the first set response to an antigen the higher the minimal immunizing dose and the lower the tolerizing dose; thus, there was a small "immunizing window." The speed of onset of immune responsiveness and the magnitude of change in it following first antigen contact depended on the "strength" of the antigen. When the antigen was "strong" the level of response increased rapidly following first antigen contact. When the antigen was "weak" a period of tolerance appeared following first antigen contact, which then gave way to a state of immunity; the "weaker" the antigen the longer the interval and the greater the magnitude of tolerance. Increasing the antigen dose tended to magnify and prolong the tolerance. The "weaker" the antigen the longer the interval between first antigen contact and the appearance of immunity. Once established, the level of immunity was not constant. Undulations in the levels of all responses were noted; the "weaker" the antigen the larger the undulations. Possible explanations for the undulations and implications of the time-dose-response curves in immunotherapy are discussed.

Animals↗
PubMed1978

Colorectal complications of renal allograft transplantation.

The occurrence of perforated sigmoid diverticulitis in a renal transplant recipient stimulated a review of colorectal complications in renal allograft recipients. One hundred twenty-five renal transplantations were performed in 113 patients between January 1968 and December 1975. Six patients (5%) were identified as having colorectal complications and five of these patients died as a direct result. Chart analysis of these 113 transplant recipients identified 55 patients as having undergone colonic evaluation (contrast enema, postmortem examination), with seven of these 55 (13%) found to have diverticulosis and major colonic complications eventually developing in four of these seven. Since the mortality from the complications of colorectal diseases in immunosuppressed patients is so prohibitive, in patients with diverticulosis and a previous history suggestive of diverticulitis, consideration should be given to exclusion from transplantation or elective segmental colectomy prior to transplantation.

Adolescent↗
PubMed1977

Prolongation of murine skin allografts by prostaglandin E1.

The effects of 16,16-dimethyl prostaglandin E2 methyl ester (di-M-PGE2) and indomethacin (an inhibitor of endogenous prostaglandin biosynthesis) on mouse skin allograft survival were studies in B10.D2 female mice receiving skin allografts from (B10.BR X B10.D2)F1 mice. Control animals with and without i.p. diluent injections had a mean allograft survival of 13.8+/-0.6 and 13.5+/-0.5 days, respectively. Daily administration of di-M-PGE2 (200 microng/kg) prolonged mean allograft survival, both when administered alone, 16.7+/-0.6 days (P less than 0.001), or with indomethacin, 4 mg/kg thrice weekly, 16.0+/0.6 days (P less than 0.005). Increasing concentrations of indomethacin (4, 6, and 8 mg/kg thrice weekly) were inversely corrleated with allograft survival ((12.7+/-0.2, 11.8+/-0.2, and 10.9+/-0.4 days, respectively), coefficient of correlation=-0.6986; P less than 0.001. Mean plasma PGE levels at the time of total allograft rejection were 879+/-80 pg/ml in control, 717+/-59 pg/ml in 100 micron g of indomethacin-treated mice, and 654+/-59 pg/ml in 200 microng of indomethacin-treated mice (P less than 0.05). Exogenous di-M-PGE2 prolonged skin allograft survival in mice. Inhibition of endogenous prostaglandin biosynthesis by indomethacin chortened allograft survival, but this effect was completely abrogated by concurrent injection of di-M-PGE2.

Animals↗
PubMed1977

Local blood flow characteristics of arteriovenous fistulas in the forearm for dialysis.

Local flow characteristics were studied in 21 patients with end-to-side cephalic vein to radial artery fistulas, constructed in the wrist for chronic hemodialysis. Intraoperative electromagnetic flow studies indicated a mean fistula flow of 242+/-72 milliliters per minute. Approximately two-thirds of the total fistula flow was derived from antegrade flow in the proximal part of the radial artery and one-third from retrograde flow in the distal part of the radial artery. Temporary occlusion of the distal part of the radial artery caused a 36% decrease in total fistula flow. Ten patients had an initial spasm of the radial artery which abated after 20 minutes. Calculations of a cross sectional area indicate that the size of the radial artery is more important than the size of the cephalic vein or the anastomosis in limiting total fistula flow. End of vein to side of artery anastomoses are preferred to end-to-end anastomoses because immediate retrograde flow in the distal part of the radial artery contributes significantly to total fistula flow.

Arm↗
PubMed1977

Blood flow measurements in arteriovenous dialysis fistulas.

Blood flows were measured in 75 arteriovenous dialysis fistulas (AVF) at the time of fistula construction. End cephalic vein to side of radial artery AVF had a mean flow of 242 +/- 89 ml. per minute which was similar to bovine heterograft AVF that also originated from the radial artery (291 +/- 67 ml. per minute). AVF originating from the brachial artery had flow rates twice those originating from the radial artery (599 +/- 163 vs. 251 +/- 89 ml. per minute), respectively). Flow rates were similar for straight arm (641 +/- 111 ml. per minute), curved forearm (561 +/- 187 ml. per minute), and curved thigh (592 +/- 134 ml. per minute) bovine AVF. Initial blood flow through arteriovenous dialysis fistulas is too low to cause heart failure, except in patients with previously compromised cardiac function. In such patients AVF from the radial artery theoretically would be preferred over brachial or femoral artery AVF.

Adolescent↗