PubMed Health⌕ Search

Biomedical subjects

N Odum

Publications and source records attributed to N Odum.

At least 109 records · Page 6Linked to original sources
PubMed1987

HLA-DP and bone marrow transplantation: DP-incompatibility and severe acute graft versus host disease.

Thirteen recipients of HLA-haploidentical, DR compatible bone marrow (BM) and the corresponding BM donors were HLA-DP typed using primed lymphocyte typing (PLT). Severe acute GVHD (greater than or equal to grade 2) developed within 3 months after BM-transplantation in all of eight recipients of DP incompatible BM, but in none of five recipients of DP-compatible BM. This difference was highly significant (p less than 0.001, Fisher's exact test). Moreover, severe acute GVHD was significantly increased in recipients of haploidentical, DR compatible, but DP incompatible BM as compared to severe acute GVHD in 88 recipients of HLA-identical BM (p less than 0.0001). In contrast, there was no difference in acute GVHD between recipients of haploidentical, DR and DP compatible BM and recipients of HLA-identical BM. The data presented here provide strong evidence for the first time that HLA-DP antigens play a role as transplantation antigens.

Bone Marrow Transplantation↗
PubMed1987

Increased prevalence of late stage T cell activation antigen (VLA-1) in active juvenile chronic arthritis.

The presence of activated T cells as judged from the reaction with monoclonal antibodies (MoAb) against (a) a late stage T cell activation antigen (VLA-1), (b) the interleukin 2 (IL2) receptor (CD25), and (c) four different HLA class II molecules (HLA-DR, DRw52, DQ, and DP) was studied in 15 patients with active juvenile chronic arthritis (JCA), 10 patients with JCA in remission, and 11 age matched, healthy controls. In addition, the distribution of T 'helper/inducer' (CD4+), T 'suppressor/inducer' (CD4+, Leu8+), T 'suppressor/cytotoxic' (CD8+), and 'natural killer' (NK) cells (CD16+) was studied. Twenty patients and six controls were investigated for the capability to stimulate alloreactivated primed lymphocytes. The prevalence of VLA-1 positive, large cells was significantly increased to 5% (median value) in active JCA as compared with JCA in remission (2%, p less than 0.05) and controls (1%, p less than 0.05), whereas no significant difference between JCA in remission and controls was observed. Except for two patients with active JCA, less than 1% IL2 receptor bearing cells were found in patients with JCA and controls. No significant difference in the prevalence and expression of the various HLA class II antigens was observed between the groups. Similarly, no significant differences in stimulatory capability in secondary mixed lymphocyte culture (MLC) were seen. The distribution of T helper/inducer (CD4+), T suppressor/cytotoxic (CD8+), and NK cells was similar in active JCA, JCA in remission, and controls. The prevalence of T suppressor/inducer (CD4+,Leu8+) cells was higher in remission JCA (17%) than in active JCA (11%) and controls (10%). This increase, however, did not reach statistical significance. In conclusion, late stage but not early stage T cell activation antigens were increased in patients with active JCA as compared with patients with JCA in remission and control, whereas some patients in remission had an increased prevalence of T suppressor/inducer cells.

Adolescent↗
PubMed1987

Immunological studies in acquired immunodeficiency syndrome: effect of TCGF and indomethacine on the in vitro lymphocyte response.

We studied the effects of exogenous T cell growth factor (TCGF) (= interleukin-2) and indomethacine on the lymphocyte transformation response in vitro to allogeneic cells, mitogens, and antigens in AIDS patients, those with AIDS-related complex (ARC), and in healthy controls. While low amounts of TCGF reduced the response of peripheral blood mononuclear cells (PBMC) to allogeneic cells in both healthy controls and AIDS patients, large amounts of TCGF augmented the response in both groups, although the response of the patients' cells were still subnormal. By depleting the PBMC for either CD4-positive or CD8-positive cells, the effect of TCGF on suboptimally mitogen-stimulated PBMC from controls was shown to be due to an increased response in both the CD4-positive and the CD8-positive cells. In contrast, with patient cells, TCGF only increased the response of the CD4-positive cells, while that of the CD8-positive cells was largely unchanged. Thus, the lack of normalization of the mitogen response of patient cells upon addition of TCGF may be largely due to unresponsiveness of CD8-positive cells to TCGF. This observation further supports the idea that CD8-positive cells are abnormal. To investigate the role of the inhibitor of TCGF production, PGE2, in AIDS, indomethacine was added to cultures of mitogen-stimulated PBMC from controls and patients. No differences were found between the three groups: the responses to PHA were slightly increased and those to Con A were unchanged.

AIDS-Related Complex↗
PubMed1986

Effect of pyrimethamine and sulphadoxine on human lymphocyte proliferation.

The in vitro effect of pyrimethamine (PYR) on human blood mononuclear cells stimulated with phytohaemagglutinin (PHA), pokeweed mitogen (PWM) and purified protein derivative of tuberculin (PPD) was studied by 14C-thymidine incorporation, by cell counting and by total DNA estimation. PYR in concentrations 10 times higher than serum values obtained in clinical practice inhibited lymphocyte proliferation irreversibly. PYR in concentrations corresponding to clinical practice quickly and irreversibly suppressed the proliferation of PWM-stimulated cells, and more slowly the proliferation of PPD-stimulated cells. The suppression of PHA-stimulated cells was reversed after one week. The increased 14C-thymidine incorporation observed in stimulated cells exposed to PYR in vitro in the early phase of proliferation did not reflect immunopotentiation but rather blocked endogenous thymidine synthesis. Sulphadoxine (SDX), added in vitro, had no effect on the lymphocytes, while SDX plus PYR had the same effect as PYR alone. Oral intake of SDX plus PYR (Fansidar) also blocked the thymidine synthesis of mitogen-stimulated lymphocytes. The possible consequences of the findings for the use of PYR in malaria prophylaxis and therapy are discussed.

Cell Survival↗
PubMed1986

Immunological studies in the acquired immunodeficiency syndrome. II. Active suppression or intrinsic defect--investigated by mixing AIDS cells with HLA-DR identical normal cells.

The lymphocyte transformation responses to mitogens (phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM)), allogeneic cells, and the antigen-purified protein derivative (PPD) were studied in six acquired immunodeficiency syndrome (AIDS) patients and in six healthy controls, each of whom was HLA-DR- and mixed lymphocyte culture (MLC)-identical with one of the AIDS patients. No evidence of suppression was observed when irradiated or non-irradiated AIDS peripheral blood mononuclear cells (PBMC) were added to cultures of HLA-DR-identical PMBC from healthy controls stimulated with the strong mitogens PHA and Con A or with allogeneic cells, but suppression may be involved in the decreased responses in cultures stimulated with PWM or PPD. Addition of supernatants from macrocultures of AIDS cells did not suppress responses of control PBMC. Thus, suppression by any lymphocyte subset or soluble factor alone cannot explain the generally severely depressed transformation responses in AIDS. Addition of heavily irradiated HLA-DR-identical PBMC from healthy controls or supernatants from these cultures led to increased responses in cultures of mitogen-stimulated AIDS PBMC and in some cultures of antigen or allogeneic cell-stimulated AIDS PBMC, which were of the same magnitude as seen after the addition of commercially obtained T-cell growth factor (TCGF). This indicates that AIDS cells are deficient in producing TCGF. Heavily irradiated AIDS PBMC were capable of restoring the transformation responses to mitogens and antigens of purified HLA-DR-identical normal T cells, indicating that AIDS cells have a normal antigen-presenting capacity and interleukin (IL-1) production. However, AIDS PBMC had a very poor capacity to stimulate normal PBMC in MLC. Together, our experiments suggest that the immune deficiency in AIDS cells may be partially due to a decreased capability of T lymphocytes to produce TCGF and that a decreased number and/or function of dendritic cells may also be involved.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Suppression of parasite-specific response in Plasmodium falciparum malaria. A longitudinal study of blood mononuclear cell proliferation and subset composition.

The present longitudinal study was designed to characterize immunosuppression during acute Plasmodium falciparum infection, during the treatment and up to 1 month after the acute stage. The proliferative responses of blood mononuclear cells (BMNC) isolated from non-immune and semi-immune malaria patients and controls to mitogens and two Plasmodium-derived stimulators (merozoites, Meroz, and soluble purified antigen, SPag) and non-related antigens were measured by [3H]thymidine incorporation. BMNC isolated before treatment (day 0) from the non-immune patients did not respond to Meroz, whereas those from controls showed a significantly higher response. The SPag responses were also low in BMNC isolated on day 0 and increased in both the non-immune and the semi-immune patients during the observation period. These findings indicate that during malaria there is a depression of the parasite-specific proliferative response. The subset composition of BMNC isolated from non-immune patients was studied in a FACS analyser. The mean cell volumes of both Leu 2+ and Leu 3+ cells were increased during the acute phase of the infection, indicating that malaria infection results in activation of both T-helper and T-suppressor cells. There was no overall reduction of the response to mitogens on day 0. However, 3 days after initiation of the treatment the mitogen response was decreased. This finding indicates that it is important to distinguish between the effects of malaria infection and of drug treatment.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

The HLA-DP polymorphism in Denmark investigated by local and international PLT reagents. Definition of two "new" DP antigens.

Lymphocytes from highly selected donors were primed for 10 days and subsequently bulk-expanded in IL 2 (TCGF) containing cultures. Two well-discriminatory PLT (CDP = Copenhagen DP) reagents against each of the DPw1-w6 specificities and one against each of the two "new" specificities, CDP4s and CDPHEI, were selected for further studies. Three combinations made in two recombinant families and four of ten HLA-A, B, and DR compatible combinations discriminated well in contrast to seven of 46 DR compatible, but HLA-A or B incompatible combinations. All reagents gave highly reproducible results, and high correlations (r-values between 0.73-1.00) for DP assignments were obtained with CDP and GNN reagents. No triplets were found for the DPw1-w6 and CDP HEI specificities. The "new" specificity CDP HEI defined in an HLA-DR/GLO recombinant family gave a coefficient of correlation with GNN 8 of 0.91. Another "new" specificity, CDP4s constitutes a subgroup ("split") of DPw4. The gene frequencies of DPw1-w6 estimated in 102 unrelated randomly selected Danes agreed with those reported for other Caucasoid populations. The gene frequencies CDP HEI and CDP4s were 0.03 and 0.08, respectively. The associations between DR3-DPw1, DR2-DPw4, and DRw6-DPw2 were confirmed. It is concluded that DP-typing with bulk-expanded reagents is a reliable and so far the only technique which can reveal the polymorphism of the DP gene products.

Cells, Cultured↗
PubMed1986

Increased frequency of HLA-DPw2 in pauciarticular onset juvenile chronic arthritis.

Thirty-six unrelated Danish patients with pauciarticular Juvenile Chronic Arthritis (PJCA) and 120 controls were typed for HLA-DPw1-w6 and the local specificity CDPHEI with bulk-expanded Primed Lymphocyte Typing (PLT) cells. The frequency of HLA-DPw2 was 52.8% in PJCA patients and 16.7% in controls (relative risk, RR = 4.5; P less than 0.001). The antigens HLA-Dw5 and/or Dw8 were present in 50% of the patients and in 21.3% of the controls (RR = 4.2; p less than 10(-3)). DPw2 was not associated (in linkage disequilibrium) with Dw5/w8 in patients or in controls, and the DP and D associations with PJCA were independent of each other. However, the combined presence of DPw2 and Dw5 and/or Dw8 gave a significantly higher risk of PJCA than each antigen alone indicating interaction of DP and DR gene products. PJCA is the first disease definitely found to be associated with a DP antigen.

Arthritis, Juvenile↗
PubMed1986

HLA-DP related suppression of mixed lymphocyte reaction with alloactivated lymphocytes.

We studied the influence of HLA class I and class II antigens on the suppression of the MLR induced by primed lymphocytes (PLs) alloactivated in vitro. The suppression of 14 different PLs of 83 MLRs was analyzed. The PLs were primed against (i) HLA-DP (SB) (ii) HLA-DR/DQ or (iii) both HLA-DP and DR/DQ. The suppression was analyzed with special reference to the sharing of HLA-antigens between (i) the stimulator in the MLR and (ii) the stimulator generating the PL. HLA-DP and HLA-DR/DQ antigens were equally capable of generating suppressor cells. When these cells were added to MLRs, the specific stimulators induced the strongest suppression (74%), while allogeic cells sharing class II antigens induced a slightly weaker suppression (66%). The suppression related to HLA-DP (60%) was almost identical to that related to HLA-DR/DQ (59%). The HLA-A, B, C related suppression was of the same magnitude (58%). The unspecific suppression (40%), i.e. no relation to known HLA-antigens, was significantly lower than the class II related suppression, but not significantly lower than the class I related suppression. The suppression of the MLR did not seem to be caused by cytotoxic cells, consumption of lymphokines, nor changes in the kinetics of the MLR. Thus, HLA-DP antigens can-like DR/DQ antigens - induce PLs with the ability to suppress the MLR in an HLA-class II (DP or DR/DQ) related, and possibly a class I related, as well as an unspecific fashion.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1986

An HLA-DR/DP recombinant family involving DPw6. Evidence for cross-reactivity between DPw6 and GNN2B.

HLA typing of an HLA-B/GLO recombinant family using bulk-expanded DP(SB) alloreactive T-cells (GNN1 to 6) as well as conventional HLA-ABC, D, DR, and DQ typing showed that a paternal recombination had taken place between HLA-DR and DQ on the one hand and HLA-DP(SB) on the other. The recombinant child was DPw4,6-heterozygous and differed in terms of class II determinants only for DPw6 from two otherwise HLA identical siblings, who were probably DPw4/4-homozygous. These siblings did not stimulate the recombinant in MLC whereas they responded to his cells indicating that DPw6 can stimulate in primary MLC. Moreover, it was possible to generate and bulk-expand DPw6-reactive lymphocytes (PLs) between MT and MA as responders and BN as stimulator. The correlation coefficient (r) between the reaction of these PLs and the GNN6 (anti-DPw6) reagents was 1.0 when tested against a panel of 71 individuals. This is the first report demonstrating that the DPw6 gene, like the DPw1-w5 genes, is located between DR/DQ and GLO. The frequency of the DPw6 antigen in 41 unrelated, randomly selected Danes was 7%. HLA-DP typing of the BN family revealed that the DPw6 positive but not DPw6 negative family members gave intermediate responses with one (GNN2B) but not with another (GNN2A) anti-DPw2-reagent. Studies of 63 healthy individuals (unrelated to the BN family) revealed seven similar discrepancies between GNN2A and GNN2B. Strikingly, all four DPw6 positive stimulators gave rise to such discrepancies indicating that the GNN2B reagent is cross-reactive and recognize a common part of the DPw2 and DPw6 molecules. No cases of GNN2A+/GNN2B- stimulators were found.

Alleles↗
PubMed1986

Effect of interleukin-2 and methylprednisolone on in vitro transformation of uremic lymphocytes.

The functional relationship in vitro between mitogen-induced lymphocyte transformation, lymphocyte response to interleukin-2 (IL-2) and steroid, and production of IL-2 was examined in patients with chronic renal failure on hemodialysis (HD) or on continuous ambulatory peritoneal dialysis (CAPD). The lymphocyte responses to optimal stimulation with phytohemagglutinin, concanavalin A, and pokeweed mitogen were depressed in lymphocyte cultures from HD patients, while CAPD lymphocyte cultures responded normally. However, at suboptimal phytohemagglutinin stimulation both CAPD lymphocyte and HD lymphocyte responses were subnormal. Uremic lymphocyte cultures were more sensitive to the immunosuppressive effect of methylprednisolone. Addition of IL-2 normalized the phytohemagglutinin responses of suboptimally stimulated CAPD lymphocyte cultures and clearly improved the mitogen responses of the HD lymphocyte cultures. Furthermore, the increased uremic lymphocyte sensitivity to methylprednisolone was normalized by addition of IL-2 to the cultures. The measured IL-2 production had clearly decreased in the HD cultures after 48 h as compared to that of the control cultures. A similar but not significant trend was also seen in the CAPD cultures. Thus, it is suggested that a deficient production of IL-2 may partly explain the reduced lymphocyte response of uremic lymphocytes in vitro.

Adult↗
PubMed1985

Immunological studies in acquired immunodeficiency syndrome. Functional studies of lymphocyte subpopulations.

The lymphocyte transformation response in vitro to mitogens (phytohaemagglutinin, concanavalin A, and pokeweed mitogen) and antigens (purified protein derivative and tetanus) was studied in three patients with acquired immunodeficiency syndrome (AIDS), three patients with pre-AIDS, and six healthy controls before and after depletion of T4- or T8-positive cells. In controls, T8-depleted lymphocytes responded as well as peripheral blood mononuclear cells (PBMC) when monocytes were added, whereas T4-depleted cells gave about 50% of this response to mitogens and no response at all to antigens. No evidence of suppression was seen when various mixtures of T4- and T8-depleted cells were made. In particular, there was a virtually linear relationship between the percentage of T8-depleted cells and the response to antigens. The PBMC of all AIDS and pre-AIDS patients had very low or absent responses to mitogens and antigens, and except in one case, this response did not increase after depletion of T8-positive cells (and addition of monocytes), indicating that these patient cells also lack suppressor activity in this assay. However, a significantly increased response to mitogens was seen when the T8-depleted suspensions were adjusted to contain 20,000 T4-positive cells per well, but the response was still significantly lower than that of similar suspensions from controls. Thus, not only are the poor responses of PBMC from AIDS and pre-AIDS patients due to a low concentration of T4-positive cells, but the responsiveness of these cells also seems deficient. Furthermore, T8-positive patient cells also have an impaired responsiveness. Our experiments do not exclude the possibility that the low response is due to a T8-negative suppressor cell, but it seems more likely that both the T4- and the T8-positive cells are deficient and/or that there is a deficiency in accessory cells. These possibilities are currently under study.

Acquired Immunodeficiency Syndrome↗
PubMed1985

The immunodeficiency of bone marrow-transplanted patients. The effect of patient lymphocytes on the response of donor lymphocytes to mitogens and allogeneic cells.

Lymphocytes from patients after bone marrow transplantation (BMT) are in most cases predominantly of the Leu-2+ (cytotoxic/suppressor) phenotypes and are almost unresponsive to mitogens. In contrast, normal Leu-3+-depleted, Leu-2+-enriched lymphocyte suspensions retain approximately 50% of the mitogenic response compared with that of unseparated cells. To investigate whether this discrepancy was due to active suppression, we selected nine BMT patients from whom sufficient numbers of cells were available and whose lymphocyte phenotypes were predominantly Leu-2+ after BMT. These post-BMT lymphocytes were tested for functional suppressor activities against donor and recipient pre-BMT lymphocytes in the lymphocyte transformation test. None of these post-BMT cells suppressed the response of donor or pre-BMT cells to phytohaemagglutinin A or concanavalin A. In contrast, the response of donor cells in mixed lymphocyte cultures to HLA-DR-different third-party cells was suppressed by highly X-irradiated post-BMT cells by approximately 40%. Addition of T-cell growth factor (= interleukin 2 (IL-2)) or X-irradiated donor cells to post-BMT lymphocytes partially restored the mitogenic response. These findings indicate that the early post-BMT cells lack production of IL-2 but are capable of responding to IL-2 and that the almost extinct mitogen response of these cells is due to immaturity rather than active suppression. The suppression of the allogeneic but not the mitogenic response might be explained by differences in the modes of activation; for example, the allogeneic response must involve the T-cell receptor, while the mitogenic response may not.

Bone Marrow Transplantation↗
PubMed1985

Specific proliferative response of human lymphocytes to purified soluble antigens from Plasmodium falciparum in vitro cultures and to antigens from malaria patients' sera.

Antigens of Plasmodium falciparum, in supernatants of in vitro cultures of the parasite were affinity purified on columns prepared with the IgG fraction of the serum of an immune individual. The purified antigens induced proliferation of lymphocytes from persons who had recently had malaria. The responses were strongest with lymphocytes from individuals infected with falciparum and ovale malaria; vivax malaria infections induced a lower level of response and lymphocytes of unsensitized individuals were little affected. Lymphocytes from unsensitized individuals did not respond to the affinity purified antigen preparations from malaria patients' sera indicating that significant amounts of non-specific mitogens were not present.

Adult↗
PubMed1984

Effect of praziquantel on human lymphocyte proliferation in vitro.

The antischistosomal drugs tartar emetic and niridazole exert immunosuppression both in vitro and in vivo. In the present study the influence of praziquantel (Biltricide), a potent schistosomicidal drug, on human lymphocyte proliferation in vitro was investigated. Praziquantel 80 micrograms/ml significantly reduced thymidine incorporation by human blood mononuclear cells stimulated with mitogens and antigens, whereas no effect could be detected in concentrations below 40 micrograms/ml. Thus, praziquantel, in concentrations as high as 30 times the peak serum concentration during therapy, has no suppressive effect on human lymphocyte proliferation in vitro.

Adult↗