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Biomedical subjects

T Mohanakumar

Publications and source records attributed to T Mohanakumar.

At least 199 records · Page 11Linked to original sources
PubMed1988

Pertussis toxin inhibits human neutrophil responses mediated by the 42-kilodalton IgG Fc receptor.

The effects of pertussis toxin (PT) on human neutrophil responses mediated by the 42-kDa IgG Fc R (Fc gamma R42) were compared with its effects on responses mediated by the FMLP receptor. Pre-treatment of neutrophils with PT completely inhibited FMLP stimulation of superoxide production and blocked over 95% of FMLP-stimulated degranulation. PT inhibited superoxide production stimulated by Fc gamma R42 cross-linking by 92%. In contrast, degranulation stimulated by Fc gamma R42 was only partially inhibited, with beta-glucuronidase release inhibited by 54%, lysozyme by 33%, and lactoferrin by 78%. With either stimulus, PT inhibition was maximal in the range from 1.8 to 2 micrograms/ml. Responses to both stimuli declined in a parallel fashion with increasing time of exposure to PT with maximal inhibition occurring after 2 h of exposure. Inhibition of FMLP responses and Fc gamma R42-mediated superoxide production, but not degranulation, correlated with ADP-ribosylation of a 45-kDa membrane protein. Inhibition by PT of Fc gamma R42-mediated responses was not due to a change in receptor number. These data suggest that activation of polymorphonuclear neutrophils via Fc gamma R42 proceeds through two pathways, only one of which is regulated by a PT-sensitive G protein.

Adenosine Diphosphate Ribose↗
PubMed1988

Monoclonal antibody to human IgG Fc receptors. Cross-linking of receptors induces lysosomal enzyme release and superoxide generation by neutrophils.

The monoclonal antibody KuFc79 binds to a determinant on the Fc receptors (Fc gamma R) of human leukocytes. We examined the biologic effects of the interaction of this antibody with Fc gamma R on human neutrophils (PMNL). The univalent Fab fragment of KuFc79 inhibits the formation of rosettes with IgG-sensitized sheep erythrocytes by as much as 91.7%. In other experiments in which PMNL were washed after exposure to Fab of KuFc79, phagocytosis of IgG-sensitized sheep erythrocytes was inhibited by 36%. Fab fragments of other mouse IgG2b monoclonal proteins did not have these effects. When PMNL are exposed to coverslips coated with univalent Fab fragments of this antibody, the Fc gamma R are removed from the surface of the PMNL. Under these conditions, rosetting could be inhibited by 85.4%. We examined cross-linking of receptor bound monoclonal antibody or its Fab fragment by either Protein A or F(ab')2 of an anti-mouse Ig. As much as 31.7% of beta-glucuronidase, a marker for lysosomal enzymes, is specifically released by cross-linking the Fc gamma R on PMNL. The generation of O2- is also induced by specifically cross-linking Fc gamma R with Fab and anti-Fab. The data constitute the first formal demonstration that cross-linking of Fc gamma R on PMNL leads to enzyme release and superoxide generation.

Antibodies, Monoclonal↗
PubMed1988

Immunological subtypes of acute lymphoblastic leukemia in north India.

Pretreatment immunologic marker analysis in 152 adult and childhood patients of ALL and ALL/lymphoma employing multiple monoclonal antibodies and hetero-antisera revealed three major subgroups, i.e. T-ALL (37.7%), N-ALL (33.1%) and C-ALL (21.5%). The early age peak was absent, males predominated in all the subgroups and T-ALL had increased incidence of thymic mass. Leucocyte counts of 50,000 X 10(6)/l were equally frequent in the three groups. T-ALL showed marked heterogeneity by showing a variety of markers such as T-helper/inducer, T-suppressor/cytotoxic, p-24, Ia and CALLA. These results show a high prevalence of unfavourable prognostic factors in ALL in our geographic region which might be related to socioeconomic and/or environmental factors.

Adolescent↗
PubMed1988

Biochemical characterization of human vascular endothelial cell-monocyte antigens defined by monoclonal antibodies.

Although the clinical relevance of endothelial cell-monocyte (E-M) antigens has been demonstrated in organ graft transplantation, very limited data exist describing the nature of these antigens. The current study presents biochemical characterization of three different surface antigens of endothelial cells and monocytes that are defined by murine monoclonals produced against gamma-interferon-induced human umbilical vein endothelial cells. The antigens gp150, gp48, and gp24 have molecular weights of 150,000, 48,000, and 24,000, respectively, under reducing conditions. The antibody binding sites of gp150 and gp48 are destroyed by pronase and chymotrypsin, indicating that the molecules are at least partly protein in nature. The inability to label the gp48 molecule with 125I using lactoperoxidase suggests that there is little protein structure exposed to the cell surface or that the molecule lacks sufficient cell surface tyrosine residues to enable detection. Immunoprecipitation of the gp24 molecule under nonreducing conditions shows that a molecule with a higher molecular weight ranging from 40,000-70,000 is detected. Although it is possible that this higher-molecular-weight species is a multimer of the 24,000 Mr species, it is also possible that there is another molecule(s) bound to the 24,000 Mr molecule. All three E-M antigens have some carbohydrate nature as evidenced by lectin-binding studies. The possible relevance of these antigens in the rejection of transplanted organ grafts is discussed.

Antibodies, Monoclonal↗
PubMed1988

Characterization of kidney cell-specific, non-major histocompatibility complex alloantigen using antibodies eluted from rejected human renal allografts.

Previous studies from our laboratories (1) have indicated that eluates prepared from rejected kidneys have antibodies not only reactive to MHC class I and class II antigens but also to antigens unique for monocytes, endothelial cells, and kidney cells. To further define the serological and biochemical nature of antigens detected by the antibodies eluted from rejected kidneys, 13 eluates prepared from rejected renal allografts and two eluates from normal kidneys were absorbed with pooled platelets, normal splenic leukocytes and/or B cells from chronic lymphocytic leukemia patients. All of the eluates failed to react with normal T and B lymphocytes by microcytotoxicity and immunofluorescence assays. However, the eluates from rejected kidneys, but not normal kidneys, reacted with peripheral blood monocytes, endothelial cells cultured from umbilical cord as well as primary kidney cells. Detailed immunohistochemical analysis of frozen kidney sections showed that the eluates from rejected kidneys reacted with structures of the cortex while sparing the structures in the medullary region. All eluates bound to the glomerulus with intense fluorescence, but not to the mesangium and Bowman's capsule, while binding to interstitial capillaries, venous endothelium, and tubular epithelium varied. More significantly, none of the eluates reacted with frozen sections of the liver, spleen, or lymph node including the endothelial lining of blood vessels in these organs. Thus, the data indicate that the eluates prepared from rejected kidneys are recognizing organ-specific antigens expressed on the kidney cells. To identify the alloantigen(s) recognized by the eluted antibodies, an immunoblot analysis was performed against phase separated membrane proteins isolated from cortical kidney cells solubilized in 2X precondensed Triton X-114. A protein of Mr. 90,000-100,000 was identified as the target non-MHC antigen to which the eluates prepared from rejected allografts were reactive. Furthermore, our results suggest a possible polymorphism among these antigens.

Endothelium, Vascular↗
PubMed1987

Pretransplant transfusions in cardiac allograft recipients.

The role of pretransplant transfusion in cardiac allograft recipients was determined retrospectively in 68 patients. Three groups were studied: group 1 (n = 29) received no pretransplant transfusion, group 2 (n = 15) received transfusion over one year prior to transplantation, and Group 3 (n = 24) received 5 or 10 50-100 ml units of random donor red blood cells or buffy coat 2-4 weeks prior to transplantation. Data were analyzed for survival, number of rejection episodes, and number of infections. Immunosuppression included azathioprine, prednisone, and antithymocyte globulin. Survival in transfused patients (groups 2 and 3) was 68% and 51% at 1 and 5 years, respectively, while in the nontransfused population (group 1) it was 35% and 16%. The incidence of rejection episodes per year of survival was similar in the three groups (group 1: 1.3, group 2: 1.1, group 3: 1.3; P greater than 0.05). The number of infections per year of survival were greater in the transfused patients but this did not achieve statistical significance (group 1: 1.0, group 2: 1.2, group 3: 1.7; P greater than 0.05). Thus, we conclude that cardiac transplant recipients who have received blood transfusions prior to transplantation may have enhanced survival over patients who have not received preoperative transfusions.

Blood Transfusion↗
PubMed1987

Antiidiotypic antibodies to human major histocompatibility complex class I and II antibodies in hepatic transplantation and their role in allograft survival.

In order to evaluate the role of antiidiotypic antibodies to anti-MHC in human liver transplant recipients, serial serum samples obtained from 10 liver recipients both pre- and posttransplantation were analyzed for the development of HLA alloantisera inhibitory activity by a microcytotoxicity inhibition assay. Seven of the 10 recipients developed strong anti-anti-HLA activity during the immediate posttransplant period, which was able to block killing of a specific alloantiserum to class I MHC antigens (44-100%). Recipients' sera were also able to block class II alloantisera (HLA-DR8) cytotoxicity of B-lymphocytes. The inhibitory activity developed 10-15 days posttransplantation, was cyclical, and was present in the immunoglobulin fraction of the serum. One patient developed specific antibodies to anti-HLA-B7 and had no inhibition for alloantisera to HLA-B8,B17,B49 and B13. Another developed antibodies capable of blocking anti-HLA B44 (mismatched donor antigen) and also cytotoxicity of HLA-B17,B49 (crossreactive group), but showed no significant inhibition of HLA-B13,B8 and B7. One recipient, transplanted across strong (1:500 titer) antilymphocyte crossmatch, rejected the graft within 1 month and failed to develop any inhibitory antibodies to anti-HLA. Two other patients who lost their grafts within 2 months posttransplantation developed only minimal (11% and 16%) and transient inhibition. Immunoprecipitation of surface-labeled, mixed lymphocyte culture stimulated lymphocytes, with sera containing inhibitory antibodies, identified membrane components of approximate molecular weights of 54,43 and 17,000, suggesting T cell clonotypic structures. Thus, these studies provide support for the development of antiidiotypic antibodies to anti-MHC in human liver transplant recipients, which may play a regulatory role in the tolerance of allograft.

Antibodies, Anti-Idiotypic↗
PubMed1987

Identification of human vascular endothelial cell/monocyte antigenic system using monoclonal antibodies.

Recent studies have suggested that non-major-histocompatibility-encoded antigens expressed preferentially on vascular endothelial cells and/or monocytes may act as immunogens leading to allograft rejection. In order to further characterize the antigens and to investigate the roles of interleukins in the induction of such antigens, three murine monoclonal antibodies (SK2H10, SK3A1, SK2F11) were produced against interferon-gamma-induced human umbilical vein endothelial cells. All three monoclonal antibodies reacted specifically with human endothelial cells cultured from umbilical veins as well as blood monocytes. Several human established cell lines with B, T, and erythroid/myeloid cell properties, as well as cell lines expressing HLA-class I and II antigens (SB, REH, HSB, K562 and HL-60) failed to react with these reagents, indicating that the binding structures on the endothelial/monocyte cell surface are distinct from HLA class I and II antigens. Furthermore, the binding characteristics of the three antibodies to endothelial cells, monocytes, and human monocytic cell line, U937, suggest that they recognize different determinants on the cell surface. Analysis of Ia-positive and Ia-negative clones of U937 demonstrated that the antibodies reacted strongly with the Ia-positive cells lines. The monoclonal SK2H10 reacted preferentially with phorbol esters-induced HL-60 and K562 cell lines; thus indicating that the antigens detected on the monocytes are associated with differentiation. These results indicate that these monoclonal antibodies to endothelial cells have specificities similar to those described for alloantisera defining the vascular endothelial cell/monocyte antigenic system and should facilitate definition of the biochemical and molecular nature of such antigens.

Antibodies, Monoclonal↗
PubMed1986

Biochemical nature of the prostate-associated antigen identified by the monoclonal antibody, KR-P8.

The KR-P8 monoclonal antibody identifies an organ-specific antigen that is associated with normal as well as malignant specimens of human prostate tissue. The antigen is secreted by cells of the prostate and is present in samples of seminal plasma. Data presented here describe the biochemical nature of the antigen that is recognized by KR-P8 as it occurs in seminal plasma and in extracts prepared from cells of the prostate tumor line, PC3. Antigen contained in seminal plasma migrated as a broad band on SDS-polyacrylamide gels in the molecular weight range of 48,000-75,000 d. A similar pattern was observed for antigen prepared from detergent extracts of PC3 cells. The antigen was found to be sensitive to treatment with trypsin and chymotrypsin and the contribution of carbohydrate residues to the structure of the molecule was shown by studies that demonstrated binding of the antigen to Concanavalin A and Soybean Agglutinin lectins. Loss of antigenicity subsequent to periodate oxidation suggested that carbohydrate units are involved in the recognition site for KR-P8 on the antigen.

Antibodies, Monoclonal↗
PubMed1986

T-lymphocyte analysis in cardiac allograft recipients treated with cyclosporine.

To assess the usefulness of circulating T-lymphocyte analysis in cardiac transplantation, T helper (Th) and T suppressor-cytotoxic (Ts-c) subsets were serially monitored in 33 cardiac allograft recipients treated with cyclosporine. The short-term prognosis of their 47 treated rejection episodes were retrospectively correlated with the changes in T-cell subpopulations. The data indicate three main findings. Reversed Th to Ts-c ratio (less than 1) was associated with a reduced incidence of rejection onset and a benign clinical course after treatment for rejection. Reversed Th:Ts-c ratio caused by antirejection therapy was associated with less chance of recurrence during the rest of hospitalization, regardless of the mode of therapy and irrespective of whether the rejection was primary or recurrent. These changes were mainly mediated by a reduction in T helper cells rather than changes in the T suppressor-cytotoxic subset or total T cells. Titration of antirejection therapy based on these T-cell dynamics may reduce either overtreatment or undertreatment. A prospective randomized study seems warranted to evaluate this approach as an alternative to a predetermined antirejection protocol.

Cyclosporins↗
PubMed1986

The importance of the Lewis system in cadaver renal transplantation.

Previous reports have suggested that Lewis (Le) antigens may exert a significant effect on cadaver renal allograft (CRA) survival, especially in black recipients in whom there is a higher frequency of Le-negative phenotypes. We review our experience with this problem in 70 donor-recipient pairs of CRA who underwent prospective Le typing and received conventional immunosuppression between 1980 and 1983. Recipient typing alone yielded the following graft survival (GS) and patient survival (PS) at 2 years by life table analysis: (a+,b;-) (n = 12) 51% GS, 93% PS; (a-, b+) (n = 44) 57% GS, 88% PS; and (a-,b-) (n = 14) 51% GS, 93% PS(P-ns for GS, PS). Recipient racial characteristics did not effect ultimate graft survival, as whites and blacks had similar two-year GS in all phenotypic groups. When Le matching was considered, no significant differences in one-year graft survivals could be ascertained between Le-matched and Le-mismatched donor-recipient pairs, and this effect persisted despite stratification for race and HLA-A,B and DR histoincompatibilities. In light of these results, we do not recommend using Lewis compatibility as a criterion for donor selection in cadaver renal allografting, as this substantially increases the difficulty in finding suitable matches, especially in the (a-,b-) recipient group.

Black People↗
PubMed1986

Detection and localization of an extra HLA locus in a karyotypically normal male by chromosomal in situ hybridization.

The codominant expression of three HLA haplotypes was found in a healthy 21-year-old Black male, whose prometaphase karyotype was normal by light microscopy. He was the sibling of an antenatally diagnosed female fetus with a partial duplication of 6p. The duplication arose from a complex presumably balanced maternal chromosome rearrangement: 46,XX,dir ins(14;6)(14pter----14p11::6p22----6p21.1::14 p11----14qter; 6pter----6p22::6p21.1----6qter). Chromosomal in situ hybridization using a tritium-labeled genomic clone corresponding to a class I HLA gene revealed two sites of hybridization: at 6p21.3, the band to which this probe has been assigned in normal individuals (Morton et al. 1984a) and a second site at 6p11. We postulate that a recombinational event during meiotic pairing in the mother led to the reintroduction into the normal chromosome 6 homolog of a small segment of the original insertion in chromosome 14 which contained the HLA-A and -B determinants.

Chromosome Banding↗