PubMed Health⌕ Search

Biomedical subjects

T Mohanakumar

Publications and source records attributed to T Mohanakumar.

At least 217 records · Page 12Linked to original sources
PubMed1985

Childhood leukemia with simultaneously expressed myeloid and lymphoid markers suggesting stem cell origin.

A case study is presented of a leukemic patient whose cells express markers of both myeloid and lymphoid cells. Cells were identified from bone marrow which expressed either myeloid antigens, lymphoid antigens, or both myeloid and lymphoid antigens, indicating a possible common stem cell capable of differentiating along either a lymphoid or myeloid cell lineage. Using specific monoclonal antibodies, 40-70% of the cells were reactive with anti-T-cell antibodies, 50% of the cells were reactive with antibodies to the common ALL antigen (CALLA), and 80-90% of the cells were reactive with antibodies directed against myeloid antigens. Using double staining techniques, some cells were found to demonstrate only myeloid markers; others, only lymphoid markers; and others, both myeloid and lymphoid markers. These results suggest that a common stem cell is capable of differentiating along both lymphoid and myeloid lineages.

Antibodies, Monoclonal↗
PubMed1985

Mechanisms of CML hyporesponsiveness in long-term renal allograft recipients.

Long-term, HLA disparate, renal allograft recipients were assessed by a dose-dependent CML (cell-mediated lympholysis) assay for evidence of donor-specific CML hyporesponsiveness. The frequency of cytolytic T-cell (CTL) precursors capable of responding to donor alloantigen was also examined by a limiting-dilution assay and application of Poisson distribution statistics. Four recipients were found to have depressed CML responses against donor class I HLA antigens (mean 2-5% specific lysis), whereas significant responses against third party targets were noted (15-60% specific lysis). These data are consistent with an antigen-specific defect in the recipient CTL effector mechanism. To determine whether or not this may be due to a deletion of anti-donor alloreactive cells, a sensitive limiting-dilution assay was developed in conjunction with Poisson distribution statistics to obtain the frequency of both anti-donor and anti-third party CTLp present in recipient PBLs. A simultaneous reduction in the number of alloreactive clones and the presence of an active suppressor population were defined, suggesting that several mechanisms may operate concurrently in long-term renal allograft recipients with well-functioning grafts.

Cytotoxicity, Immunologic↗
PubMed1985

Localization of a normal prostatic secretory product using the monoclonal antibody KR-P8.

We previously reported that the monoclonal antibody KR-P8 detects a prostate organ-specific antigen that is distinct from other markers such as prostatic acid phosphatase and prostate specific antigen. In this report we demonstrate that the antigen recognized by KR-P8 is among the secretory products of both normal and malignant prostatic epithelium. Immunoperoxidase staining patterns showed that the antigen was concentrated on the luminal surfaces of the glandular epithelial cells of prostate, and also that the antigen was localized within secretory vacuoles of cells of the prostate tumor line PC3. In addition, using an immunoblotting assay the KR-P8 binding antigen was detected in the growth media of PC3 cells and also found to be present in human urine and seminal plasma. The data suggest that the antigen recognized by KR-P8 may be a useful marker for studying the secretory processes of the prostate gland.

Antibodies, Monoclonal↗
PubMed1985

Cyclosporine in cardiac transplantation.

Cyclosporine is a new immunosuppressive drug that acts early in the exposure of a host to allogeneic stimulation. It is a peptide of fungal origin. It has selective action on T cells, leaving the other cells of the immune system intact. It acts by preventing the function of the early activation signals of T cells, such as the acquisition of receptors for Il 2 and Il 1. It is lipophilic, moderately well absorbed by the gut, and metabolized by the liver. Factors affecting absorption or hepatic metabolism alter the amount of cyclosporine available in the circulation. Circulating levels can be measured by radioimmunoassay or HPLC. Doses should be tailored to trough levels taken approximately 12 hours after an oral or intravenous dose or to individual pharmacokinetic curves. The drug is nephrotoxic, hepatotoxic, and neurotoxic. In addition, cyclosporine has been associated with hypertension, hemolytic-uremic syndrome, increased incidence of intravascular thrombotic events, hypertrichosis, gum hyperplasia, pericardial effusion, and lymphoproliferative disorders. Despite these complications, cyclosporine usage seems to have improved short-term cardiac allograft survival and to have reduced the complications associated with side effects of steroids. As a result, cyclosporine has spawned a resurgence of interest in cardiac transplantation, which will be of great benefit in prolonging the lives of patients with end-stage cardiac disease.

Animals↗
PubMed1985

In vitro evidence for defective afferent immune function in long-term renal allograft recipients.

Experiments were designed to evaluate afferent immune functions in 21 long-term (greater than or equal to 3 years) renal allograft recipients by using in vitro assays that included autologous and allogeneic mixed lymphocyte reactions (AMLR and allo-MLR), proliferative responses to a soluble antigen (tetanus toxoid), and the ability to generate cytotoxic T lymphocytes (CTL) following stimulation in an AMLR. The results showed that allograft recipients generated responses in the allo-MLR (means = 84,789 +/- 8242) that were comparable to those exhibited by normal controls (means = 86,082 +/- 7423). Likewise, mean responses in the AMLR were similar in recipients and controls (14,937 +/- 3243 versus 16,101 +/- 3005), although a greater percentage of recipients generated AMLRs below 5000 cpm than did normals (8/21 versus 4/20). However, 13 recipients analyzed for responsiveness to tetanus toxoid were shown to generate mean proliferative responses that were significantly depressed below normal (18,095 +/- 5545 versus 48,935 +/- 8813, P less than 0.001). Furthermore, despite significant proliferation in the AMLR means = 27,648 +/- 5168), 8 recipients generated significantly lower CTL activity in AMLR cultures than normal controls (mean percentage of cytotoxicity = 10.3 +/- 4.7 versus 24.9 +/- 4.7, P less than 0.05). These recipients generated normal CTL levels against allogeneic target cells following stimulation in an allo-MLR. Thus, these studies provide experimental support for the existence of altered T helper cell-mediated functions in long-term renal allograft recipients.

Humans↗
PubMed1985

Characterization of human IgG Fc receptors.

A murine monoclonal antibody, KuFc79, has been developed that reacts with human IgG Fc receptors on monocytes, B lymphocytes, and granulocytes. The specificity of KuFc79 for Fc receptors was demonstrated by the ability of Fab fragments to block Fc-mediated phagocytosis by monocytes. This finding was further substantiated by the decrease of KuFc79 binding to monocytes and granulocytes (58 and 70%, respectively) after modulation of surface IgG receptors with aggregated IgG. In addition, Fab KuFc79-conjugated Sepharose was used to isolate functional IgG Fc-binding molecules from soluble extracts of the human monocyte-like cell line U937. By immunoprecipitation, it was further shown that KuFc79 immunoprecipitated molecules of 42,000 and 70,000 daltons from U937 and a human lymphoblastoid cell line, SB. A lower m.w. species of approximately 33,000 was also precipitable from granulocytes. Extensive microheterogeneity of these molecules was noted by isoelectric focusing, which appears to be due to differential sialation.

Animals↗
PubMed1985

Ultrastructural analysis of acute lymphoblastic cells: peanut lectin binding correlates with degree of differentiation of the leukemic cells.

Peanut agglutinin (PNA) has been shown to bind selectively to immature cells. Bone marrow cells from some children having acute lymphocytic leukemia (ALL) bind PNA while cells from other ALL patients do not bind, the significance being that the patients whose cells bind PNA have a poorer prognosis than those not binding PNA. In the present study, PNA was conjugated to horseradish peroxidase and the two cell types were compared. Cells binding PNA are immature compared with the non-PNA-binding cells.

B-Lymphocytes↗
PubMed1985

A prospective randomized trial of pretransfusion/azathioprine/prednisone versus cyclosporine/prednisone immunosuppression in cardiac transplant recipients: preliminary results.

Cyclosporine has gained acceptance as the immunosuppressive agent of choice in cardiac transplantation, but the validity of this assumption has yet to be established. Since January 1983, 25 patients have been randomly assigned to receive either conventional immunosuppression (azathioprine/antithymocyte globulin/prednisone) and pretransplant transfusion (PAAP, n = 11) or cyclosporine immunosuppression (cyclosporine and prednisone [CyA], n = 14). There was no difference in the age distribution (41 +/- 9 vs 38 +/- 11 years), indications for transplantation, preoperative serum creatinine level (1.2 +/- 0.2 vs 1.4 +/- 0.3 mg/dl), or postoperative follow-up time (13.5 +/- 5.4 vs 13.5 +/- 5.2 months). Mortality was not different (PAAP = 2, CyA = 3) and there was no difference in rejection episodes per patient (PAAP = 1.8, CyA = 1.9). Patients in the PAAP group had more serious infections (PAAP = 8, CyA = 3; P less than .02), but those in the CyA group developed a greater incidence of systemic hypertension (PAAP = 1, CyA = 10; p less than .02), pericardial effusion (PAAP = 0, CyA = 6; p = .05), and impaired renal function (creatinine 1.5 mg/dl, PAAP = 2, CyA = 11; p less than .02). Thus it appears that in this small series, cyclosporine is not associated with a significant increase in early survival. It does appear that patients on PAAP immunosuppression develop a greater number of serious infections, but the incidence of rejection episodes appears to be the same. Renal dysfunction and hypertension in patients receiving cyclosporine continue to be long-term concerns and may add to the morbidity and mortality of patients treated with this immunosuppressive regimen.

Adult↗
PubMed1984

Orthotopic cardiac transplantation in a Veterans Administration hospital.

Of 57 patients referred to the McGuire Veterans Administration Medical Center, Richmond, Va, for evaluation for cardiac transplantation, 18 received allografts. The overall graft survival rate was 67% from two to 24 months after transplantation. In 15 recipients receiving immunosuppression with rabbit anti-human thymocyte globulin, prednisone, and azathioprine, previous transfusion and HLA-DR matching resulted in improved graft survival. In three patients receiving cyclosporin and prednisone, hypertension, nephrotoxicity, and hepatotoxicity were seen. All surviving recipients were in functional New York Heart Association class 1 or 2. The cost to the Medical Center was $23,275 per transplant. The results achieved at the center suggested that a regionalized cardiac transplant program can be established within the VA health care system with acceptable clinical results and significant financial savings.

Adult↗
PubMed1984

Class I antibody induction by rat endothelium.

Supradiaphragmatic vein grafts were transplanted from ACI (RT1a) to Fisher (RT1(1)) rats to determine whether the endothelium and/or circulating passenger leukocytes were necessary for the induction of an antibody response. Vein grafts from immunosuppressed and irradiated donors induced lymphocytotoxic and hemagglutinating antibody in recipient rats. In addition, IgG antibody produced in Fisher recipients was found by indirect immunofluorescence to donor endothelium. When the endothelium was removed from donor veins either by collagenase or by scraping the intima, no antibody resulted after transplantation. The lymphocytotoxic and hemagglutinating antibodies and the antibodies identified by indirect immunofluorescence were removed by absorbing the Fisher serum in ACI red blood cells. The endothelium seems to be capable of inducing Class I antibodies when allogeneically transplanted as vein grafts.

Animals↗
PubMed1984

Clinical significance of in situ detection of T lymphocyte subsets and monocyte/macrophage lineages in heart allografts.

Seventy fresh frozen biopsies of 22 human heart allografts were stained with mouse antihuman monoclonal antibodies (OKT-4, OKT-8, and OKM-1) using the immunoperoxidase method. The numbers of infiltrating cell phenotypes were correlated with patients' clinical status and histopathological diagnoses of the biopsies. At the clinically stable stage the number of OKT-4-positive cells (T-4 cells, helper/inducer), OKT-8-positive cells (T-8 cells, suppressor/cytotoxic), OKM-1-positive cells (M-1 cells, monocyte/macrophage) and T4/T8 ratio were lowest. During the early stage of rejection T-4 cells increased to the highest values. T-8 cells also increased significantly and T4/T8 ratio increased to the peak level as well. During the later stage of rejection, T-8 and M-1 cells increased to the highest values and T-4 cells and T4/T8 ratio decreased. After the treatment of rejection T-4 cells continued to decrease and T-8 cells and M-1 cells decreased to intermediate levels, but T4/T8 ratio still remained level. The numbers of T-4 cells, T-8, cells and M-1 cells were closely associated with the histopathologic severity of rejection. These results were also correlated with the allografts' prognoses. Interestingly, high T4/8 ratios with high number of T-4 cells in biopsies during the quiescent period were often followed by rejection episodes within 7 days, even though the pathological diagnoses were mild rejection. Another important finding was that after the treatment of rejection, persistent M-1 cells and low T4/T8 ratios in situ were frequently accompanied by recurrent rejections. Thus, monitoring of infiltrating cell phenotypes may be beneficial in the management of clinical cardiac transplantations.

Antibodies, Monoclonal↗
PubMed1984

Pretransplant warm B cell antibodies in recipients of primary and retransplanted cadaver renal allografts.

Eighty-four recipients of cadaveric renal allografts were retrospectively crossmatched for donor-specific pretransplant B cell antibody. Of these, 28 were found to be positive for the antibody and 56 were negative. Actuarial survival analysis over six years revealed a slightly better graft survival overall in the B-cell-negative group as compared with the B-cell-positive group (P less than 0.07). These patients were further subgrouped into those who received primary transplants and those who were retransplanted. Fifty-four percent of the B-cell-positive group (15/28) consisted of retransplants, and only 13% (7/56) of the B-cell-negative group were retransplants. When considering primary transplants only, B-cell-negative and B-cell-positive groups had similar graft survival rates (P less than 0.25). When retransplants only were considered, the graft survivals of the B-cell-positive and B-cell-negative groups were comparable (P less than 0.32). The most significant differences were observed when comparing the B-cell-positive primary transplant group with the B-cell-positive retransplanted group. The primary transplants fared consistently better at all time intervals (P less than .007). Conversely, when primary and retransplants in the B-cell-negative group were compared, no differences were noted (P less than 0.29). Our results suggest that the identification of pretransplant B-cell antibodies may be indicative of a poorer allograft survival prognosis in patients who have been previously transplanted.

Autoantibodies↗
PubMed1984

Characterization of a monoclonal antibody, KR-P8, that detects a new prostate-specific marker.

This report characterizes a prostate-specific monoclonal antibody, KP-P8, which was prepared against the human prostate cell line PC3. The antigen detected by KR-P8 was identified on the surfaces of 90% of cells of the PC3 line, as well as on 67% of cells of the Du-145 prostate line, but it was absent from the surfaces of normal peripheral blood leukocytes and cells of a number of lymphoblastoid lines. As judged by immunoperoxidase staining techniques, KR-P8 reacted with the glandular epithelium of all specimens of normal, benign hypertrophic, and malignant prostate glands tested. However, no reactivity was noted with numerous other human tissues including normal bladder, lung, liver, kidney, testis, colon, parotid gland, thyroid gland, and spleen. These results indicate that the antigen detected by KR-P8 is prostate organ-specific. Competitive blocking studies showed that the antibody did not recognize the previously described prostate-specific antigen or the alpha-Pro-3 antigen described by other investigators. The KR-P8 antibody also did not bind to purified prostatic acid phosphatase. The presence of the KR-P8 antigen was demonstrated in cell-free preparations of dilute seminal plasma by radioimmunoassay, indicating that this antigen is secreted by the glandular cells of the prostate gland. The clinical significance of this marker was demonstrated by its ability to identify prostate metastases of the lymph node.

Animals↗