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Biomedical subjects

J M Reuben

Publications and source records attributed to J M Reuben.

At least 55 records · Page 3Linked to original sources
PubMed1985

In vitro modulation of purine enzyme metabolism and lymphocyte surface marker expression by thymosin fraction 5 in homosexual males.

Thymosin fraction 5 (Thymosin) has numerous immunoregulatory activities including modulation of enzymes involved in lymphocyte maturation. The effect of Thymosin on the purine metabolic enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5' nucleotidase (5'NT) in null and T-enriched peripheral blood lymphocytes from sexually active asymptomatic homosexual males (AS), patients with the AIDS-related symptom complex (ARC), and those with acquired immune deficiency syndrome (AIDS) was examined and compared to its effect on lymphocytes from healthy heterosexual controls. Mean ADA activity was significantly higher in null cells from fourteen AIDS patients than in five asymptomatic homosexuals, ten ARC patients, or 27 controls. Mean PNP activity was significantly elevated in null-enriched lymphocytes from ten ARC and fourteen AIDS patients compared to controls. No differences in these enzymes were found in T-enriched cells from any group. 5'NT was markedly decreased in both null and T lymphocytes in all homosexual groups relative to controls. Homosexuals had significantly elevated percentages of OKT10 positive and Ia positive lymphocytes compared to controls. Thymosin at an optimal concentration of 150 micrograms/ml caused significant decreases in mean ADA and PNP activity in null lymphocytes from ARC + AIDS patients along with a significant decrease in the percentage of OKT10 positive lymphocytes. No phenotypic changes were seen in AS or control lymphocytes. The data suggest that Thymosin has a maturational effect in vitro on immature T cells from symptomatic homosexuals.

5'-Nucleotidase↗
PubMed1985

Immune recovery following allogeneic bone marrow transplantation.

A total of 144 evaluations of cell surface markers and cellular immune functions were carried out in 57 patients undergoing allogeneic bone marrow transplantation for acute leukemia in remission and relapse and for aplastic anemia. The periods tested were pretransplant, and 1-3, 4-6, 7-12 and more than 12 months posttransplant. The determination consisted of lymphocyte counts; lymphocyte surface marking using OKT3, OKT4, and OKT8 antibodies; and determination of adherent cells, lysozymes and antibody dependent cellular cytotoxicity (ADCC) against chicken red blood cells, human red blood cells, and CEM cells. Natural killer cells were determined against K562 target cells. Lymphoblastic responses were tested after stimulation with pokeweed mitogen (PWM), concanavalin-A (Con-A), and phytohemagglutinin (PHA). We found that the progression in the leukemic state (first remission, second remission, and relapse), prior to transplantation was paralleled by a decrease in T4 lymphocytes (976/microliter +/- 462; 411/microliter +/- 222; 372/microliter +/- 419; P = .04). There was a lack of helper cells and an inverted T4:T8 ratio beyond one year posttransplant independent of graft-versus-host disease status. Lymphocyte functions persisted to be depressed for more than one year. We found a direct correlation of T4 helper cells and an inverse correlation of T8 suppressor cells with lymphoblastic responses to mitogens. It is hoped that the longitudinal evaluations of immune functions after allogeneic bone marrow transplantation, and the characterization of the immune defects seen may lead to better immunorestorative treatments.

Adolescent↗
PubMed1985

Treatment of acquired immunodeficiency syndrome--related Kaposi's sarcoma with lymphoblastoid interferon.

Twelve homosexual patients with Kaposi's sarcoma associated with the acquired immune deficiency syndrome (AIDS) were treated with a preparation of purified human lymphoblastoid interferon (Wellferon [Burroughs Wellcome, Research Triangle Park, NC]). They were given a dose of 20 X 10(6) U/m2 intramuscularly daily for approximately two months. Responders continued their treatment on a maintenance schedule of 20 X 10(6) U/m2 three times a week. Four patients experienced complete remissions, and four experienced partial remissions that resulted in a total response rate of 67%. The median duration of treatment was 14 weeks (7 to 28+ weeks), and the median response duration was 28+ weeks (19 to 29+ weeks). Of the four patients in complete remission, one relapsed at 25 weeks and one at 26 weeks; the other two remained in complete remission at 28 and 29+ weeks. The clinical toxicity consisted of chills, fever, fatigue, and asthenia. Hematologic toxicity was similar to that previously described for other preparations of alpha-interferon and consisted of moderate leukopenia and thrombocytopenia. Asthenia, a condition present in all 12 patients, was severe in 50%. A minimal tumor burden, the absence of circulating interferon before treatment, and a performance status of greater than or equal to 90% on the Karnofsky scale were related to an improved response rate. Measurement of immunologic parameters showed significant declines in the already impaired T cell levels, lymphocyte blastogenic response to concanavalin A, monocyte-mediated antibody-dependent cellular cytotoxicity, and monocyte-adherence. Activation of natural killer cells was not noted, and no life-threatening infections occurred during treatment. These data suggest that human lymphoblastoid interferon is an active agent in the treatment of Kaposi's sarcoma, and its use warrants further study in a larger number of patients.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Impaired in vitro interferon, blastogenic, and natural killer cell responses to viral stimulation in acquired immune deficiency syndrome.

The in vitro immune response to herpes simplex virus (HSV), type 1, strain 539, HSV type 2, strain 316D, and cytomegalovirus was studied in 20 patients (14 with acquired immune deficiency syndrome, four with the acquired immune deficiency syndrome-related symptom complex, and two sexually active asymptomatic homosexuals) and 18 heterosexual healthy controls. Peripheral blood mononuclear cells were cultured with 2 X 10(5) plaque-forming units of heat-inactivated viruses, their lymphocyte blastogenic responses were measured after 5 days in culture by [3H]-thymidine incorporation, their interferon production was measured after 24 hr and 5 days, and natural killer (NK) cell activation was measured after 24 hr and 5 days of culture. Blastogenic responses to viruses were significantly low for only HSV, type 1:1.75 X 10(3) cpm in patients' cells compared to 6.36 for controls. Interferon responses to all three viruses were significantly low at both 24 hr and 5 days; e.g., HSV, type 1:139 IU/ml in patients' cells compared to 777 for controls at 24 hr. NK cell responses of patients were lower than those of controls when tested fresh and after 24 hr of incubation: 6.1 versus 11.7% and 9.2 versus 16.8% target cell lysis, respectively. Exposure to viruses boosted NK cell responses of both patients' and controls' cells, but boosting was generally greater among the normal rather than the patients' cells. The abnormalities of response were present in all three patient groups. Addition of interleukin-2 in vitro increased the patient and control blastogenic and NK responses but did not augment the interferon responses. The in vitro responses to both HSV, type 1, and HSV, type 2, correlated significantly with our conventional assays of the percentage and absolute level of T4+-helper lymphocytes in the blood and the blastogenic responses to mitogens, such as phytohemagglutinin, pokeweed mitogen, and concanavalin A. This system should be useful for the study of host defense in acquired immune deficiency syndrome patients and those in high-risk groups, and also for the in vitro evaluation of immunomodulators.

Acquired Immunodeficiency Syndrome↗
PubMed1985

IL-2 production and response in vitro by the leukocytes of patients with acquired immune deficiency syndrome.

In order to investigate the nature of the T cell defect associated with the acquired immune deficiency syndrome (AIDS) we studied the ability of peripheral blood mononuclear cells from 8 patients with Kaposi's sarcoma (KS), 2 with opportunistic infection (OI), 23 with AIDS-related symptoms complex (ARC) without KS or OI (ARC), and 29 heterosexual controls to produce interleukin II (IL-2) on phytohemagglutinin (PHA) stimulation and to respond to exogenously supplied IL-2. Patients with AIDS as well as those with ARC produced adequate levels of IL-2 in response to lectin stimulation when compared to controls (AIDS, 3.07 +/- 1.98 units; ARC, 3.03 +/- 1.89 units; controls, 3.75 +/- 1.52 units). However, the ability of these patients' cells to respond in vitro to exogenously supplied IL-2 as measured on short-term PHA-stimulated T cell blasts, was found to be severely impaired in patients with AIDS and ARC (AIDS, 22.4 +/- 6.0 X 10(-3) cpm; ARC, 20.1 +/- 4.2 X 10(-3) cpm; control, 41.4 +/- 4.2 X 10(-3) cpm). This impairment was associated with diminished expression of the IL-2 receptor on 7-day-old lectin-stimulated T cells from both patient groups (AIDS, 17.7 +/- 5.7; ARC, 36.8 +/- 4.4; control 71.8 +/- 1.7). These results should be considered when IL-2 is proposed as potential therapy in the treatment of AIDS. They also suggest that the nature of the AIDS defect is related to impaired hormone receptor expression.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Elevated adenosine deaminase and purine nucleoside phosphorylase activity in peripheral blood null lymphocytes from patients with acquired immune deficiency syndrome.

The purine metabolic enzymes adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) are important in lymphocyte differentiation, and genetic deficiencies of either enzyme have been associated with hereditary immunodeficiency states. Both ADA and PNP activity were measured in null cell-enriched and T cell-enriched peripheral blood lymphocytes from 16 patients with the acquired immune deficiency syndrome (AIDS), seven patients with the AIDS-related symptom complex (ARC), and seven asymptomatic homosexuals. ADA activity in nmol/10(6) lymphocytes/h was significantly elevated in null lymphocytes from AIDS (161 +/- 12) as compared with 23 healthy heterosexual controls (127 +/- 8;P less than .025). PNP activity was also significantly increased in null lymphocytes from AIDS patients (96 +/- 10;P less than .005) as well as those from ARC patients (84 +/- 11:P less than .025) relative to controls (61 +/- 5). No significant differences in enzyme activity were noted in T cell-enriched cells in any group. Along with elevated enzyme activity, AIDS patients had small yet significant increases in the percentages of HLA-DR (P less than .025), terminal deoxynucleotidyl transferase (TdT) (P less than .0001), and peanut agglutinin receptor (P less than .0001) positive lymphocytes in the null fraction compared with controls. TdT-positive cells appeared morphologically as large lymphoblasts with irregular nuclei. The data imply that the cellular immune deficiency in AIDS is not a result of deficiencies in lymphocyte ADA or PNP activity, but is more likely associated with an increase in an immature and/or activated lymphocyte subset.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Abnormal lymphocyte response to exogenous interleukin-2 in homosexuals with acquired immune deficiency syndrome (AIDS) and AIDS related complex (ARC).

Interleukin-2 (IL-2) production as well as the response of lymphocytes to exogenous IL-2 was measured in asymptomatic homosexuals, patients with acquired immune deficiency syndrome (AIDS), and homosexuals with prodromal symptoms. IL-2 production following lectin stimulation was not significantly different in homosexuals compared to age matched heterosexual controls. In contrast, the response of lymphocytes to exogenous IL-2 was significantly decreased in AIDS and homosexuals with prodromal symptoms compared to asymptomatic homosexuals and heterosexual controls. These data, combined with the data of others, suggest that an underlying immune defect in AIDS is abnormal IL-2 receptor expression and resultant poor IL-2 response.

Acquired Immunodeficiency Syndrome↗
PubMed1984

T cell surface antigen expression on lymphocytes of patients with AIDS during in vitro mitogen stimulation.

Surface marker expression on peripheral blood mononuclear cells (PBMC) was evaluated daily in PHA- and PWM-stimulated cultures of eight AIDS patients and eight normals. Before culture, the patients' cells showed the characteristic decrease in OKT 4+ cells (normals 40.4%, patients 22.3%; P less than 0.001), increase in OKT 8+ cells (normals 27.6%, AIDS 38.4%; P = 0.002), increase in OKT 10+ cells (normals 15.5%, AIDS 42.8%; P = 0.002), and increase in HLA-DR+ cells (normals 11.4%, AIDS 28.7%; P = 0.01). The percentage of OKT 11+ cells remained unchanged, while the percentage of OKT 3+ cells dropped over the first 2 days in PHA but not in PWM cultures of both groups (PHA: normals 69.8% to 35.1%; P = 0.001, AIDS 56.5 to 38.5%; P = 0.001, PWM: normals 62.8%-65.9%, AIDS 66.8% to 63.9%), and recovered in both groups by day 5. In PWM cultures OKT 3+ cells increased significantly in normals but not in AIDS (normals 62.6%-77.7%; P = 0.04, AIDS 61.8 to 48.7%). OKT 4 expression decreased in normal PHA cultures after 1 day (38.9% to 29.6%; P = 0.05) and then recovered by day 5. Its expression increased in AIDS PHA cultures by day 5 (18.0%-41.1%; P less than 0.001). The final percentage of OKT 4+ cells in AIDS cultures was within the normal range (35.0%-49.0%). OKT 8 expression increased in both study groups after PHA stimulation (normals 29.5%-50.4%; P = 0.002, AIDS 37.4%-50.7%; P = 0.02) and in normals but not AIDS after PWM stimulation (normals 28.9%-35.5%; P = 0.004, AIDS 38.5%-35.6%). Because of the relative changes in expression of OKT 4 and OKT 8, the 4/8 ratio declined in the normal PHA cultures (1.89 to 1.03; P = 0.1) and increased in the AIDS cultures (0.68-1.18; P = 0.09). Also, the sum of OKT 4+ and OKT 8+ cells in PHA cultures increased from 68% to 94% whilst expression of OKT 11 remained unchanged, indicating co-expression of these antigens on individual cells. Both PHA-and PWM-stimulated normal cells showed an increase in OKT 10 (PHA 16.0%-53.4%; P = 0.01, PWM 16.1%-33.9%; P = 0.03) and HLA-DR (PHA 8.6%-27.3%; P = 0.03, PWM 12.5%-26.6%; P = 0.07). In AIDS PHA cultures this did not change, and in their PWM cultures OKT 10 expression declined (44.8 to 23.0%; P = 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1984

Immunologic studies of the acquired immune deficiency syndrome: relationship of immunodeficiency to extent of disease.

Immunologic and conventional laboratory studies were done in 135 previously untreated subjects including 28 (20.7%) symptom-free homosexuals and 74 (54.8%) with ARC and 33 (24.5%) with AIDS. More than half of all patients had abnormal percentages of lymphocytes, percentages of T3+ cells, percentage and absolute number of T4+ cells, percentage of T8+ cells, T4/T8 ratio, monocyte adherence, and serum thymosin alpha 1. Most immune variables worsened with progressive disease. Low lymphocyte 5'nucleotidase increased suppressor cell activity, and impaired IL-2 and alpha interferon production and response suggest diminished mature and increased immature peripheral blood and tissue T cells. These findings suggest approaches to staging, prognostication, and treatment for AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Decreased 5' nucleotidase activity in lymphocytes from asymptomatic sexually active homosexual men and patients with the acquired immune deficiency syndrome.

5' Nucleotidase (5'NT) is an ectoenzyme associated with the plasma membrane of most mammalian cells. Low 5'NT activity has been observed in peripheral blood lymphocytes from patients with immunodeficiency states. 5'NT activity was measured in null and T-enriched lymphocytes from asymptomatic homosexual men and from 20 men with various degrees of the acquired immune deficiency syndrome (AIDS). Asymptomatic homosexuals were self-referred because of their concern about AIDS and were not necessarily representative of homosexuals in the general population. Enzyme activity was significantly decreased in both null (7.0 +/- 2.4 nmol/10(6) cells/h) and T-enriched (12.0 +/- 6.0 nmol/10(6) cells/h) lymphocytes in homosexuals as compared to lymphocytes from aged-matched heterosexual male and female controls (null = 10.8 +/- 6.5 and T = 22.3 +/- 10.6, P less than .0001 and .008, respectively). Decreased activity was present regardless of whether the patients were asymptomatic, had prodromal symptoms such as fever, lymph node enlargement, weight loss and diarrhea, or had opportunistic infections or Kaposi's sarcoma. Homosexuals had a significantly higher fraction of lymphocytes expressing the activation antigens T10 (20% +/- 3.3%) and Ia (13% +/- 2.9%) than controls (11% +/- 1.8% and 5% +/- 0.8%, respectively, P less than .05). They also had a significantly lower fraction of OKT4-positive helper lymphocytes than controls (22% +/- 3.4% v 35% +/- 2.2%, P less than .05). 5'NT activity in lymphocytes enriched for null cells from homosexuals correlated inversely with the percentage of Ia-positive lymphocytes (r = -.655; P less than .02). There was no correlation between 5'NT activity and the percentage of T4- or T8-positive lymphocytes or the T4/T8 ratio. Moreover, 5'NT activity was significantly decreased in both OKT4 (P less than .025) and OKT8 (P less than .05) enriched lymphocytes in homosexuals compared to controls. The data suggest that decreases in 5'NT may be a generalized defect of the peripheral blood T lymphocytes from active homosexuals that is independent of increases or decreases in specific T subpopulations or clinical status. It may contribute to the pathogenesis of AIDS.

5'-Nucleotidase↗
PubMed1984

Immunological characterizations of patients with acquired immune deficiency syndrome, acquired immune deficiency syndrome-related symptom complex, and a related life-style.

Immunological, hematological, and biochemical studies were done at the time of referral in 135 homosexual subjects, 28 of whom were symptom free (SF), 74 of whom had the acquired immune deficiency syndrome (AIDS)-related symptom complex (ARC), and 33 of whom had AIDS with Kaposi's sarcoma, opportunistic infection, or both. Of 38 laboratory parameters, 11 were significantly different than controls in the SF patients, 19 in the ARC patients, and 20 in the AIDS patients. In SF patients, delayed hypersensitivity was significantly suppressed for 6 of 12 recall antigens. In addition, the percentage of circulating lymphocytes, the percentage of T3+ cells, the percentage and absolute number of T4+ cells, the T4/T8 ratio, the blastogenic responses to phytohemagglutinin, pokeweed mitogen, and concanavalin A were depressed significantly in this group. In contrast, the percentage and absolute granulocyte count, the serum lysozyme, and the serum thymosin alpha 1 were significantly elevated in these patients. In patients with more advanced disease (ARC and AIDS), immunological and hematological parameters tended to worsen. Thus, in the AIDS patients the white blood cell count, percentage, and absolute T11+ cells, absolute T3+ cells, percentage of T4+ cells and absolute level of B-cells, as well as the monocyte adherence and delayed hypersensitivity responses to 12 of 12 recall antigens were depressed. Serum levels of thymosin alpha 1 were equally elevated in all three groups. Serum interferon was found in 15 of 18 opportunistic infection patients with or without Kaposi's sarcoma, in 3 of 9 Kaposi's sarcoma patients without opportunistic infection, but in none of the ARC or SF patients. This study has demonstrated that SF sexually active homosexuals have a characteristic pattern of immune deficiency and that immunodeficiency worsens as one compares SF to ARC to AIDS patients. The study has provided a data base for the development of prognostic criteria and for characterization and evaluation of immunorestorative and immunomodulatory therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Delayed hypersensitivity responses of cancer patients to recall antigens using a new "Multitest" applicator.

Testing of delayed-type hypersensitivity to recall antigens is acknowledged to be a useful assessment of cell-mediated immunity in cancer patients. The conventional method, however, has suffered from a lack of standardized antigens and variability owing to the method of application of the recall antigens. The Multitest-CMI system by the Merieux Institute offers an alterative. It employs standardized antigens and a single-stroke applicator, which is simpler to use and presumably subject to less variation. The present study compares the conventional and Multitest batteries done over an 8-month period in 403 cancer patients. The results suggest that the Multitest is easier to administer and is tolerated better by patients than the conventional method. Furthermore, the Multitest can detect recall antigen anergy or reactivity and correlates well in degrees of reactivity to the individual test battery. Consequently, Multitest-CMI can be substituted for the conventional battery in skin testing for immunocompetence in cancer patients.

Histocompatibility Antigens Class II↗
PubMed1983

Immunological studies of male homosexuals with the prodrome of the acquired immunodeficiency syndrome (AIDS).

Homosexual patients who mainly had the prodrome of the syndrome of opportunistic infection and Kaposi's sarcoma were studied immunologically. Patients showed diminished delayed hypersensitivity to recall antigens, diminished lymphocyte blastogenic responses, a suppressor cell for lymphocyte proliferative responses, low helper cells and an inverted helper:suppressor ratio. The patients had low levels of adherent monocytes. NK cell activity and antibody dependent cellular cytotoxicity were normal. Virtually all patients showed elevated serum thymosin alpha 1 levels and elevated serum lysozyme levels. The most consistent findings were the low helper cells, inverted helper:suppressor ratio and elevated serum thymosin alpha 1 and lysozyme. The patients with the prodrome should be subjected to therapeutic research with immunorestorative drugs.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Protection against experimental echinococcosis by non-specifically stimulated peritoneal cells.

Infection of cotton rats with Echinococcus multilocularis or vaccination with BCG, or its cell walls, activates peritoneal cells to kill the protoscolices of the parasite in vitro and protects laboratory animals against the cestode. To determine whether other 'non-specific' stimuli would also protect against the parasite, cotton rat peritoneal cells were activated in vivo with PHA and transferred to recipients 3 days later. The recipients, controls and PHA-treated animals were then inoculated with the parasite; 3 days after inoculation other untreated infected animals received cells activated in vivo with PHA. PHA-activated cells, the PHA treatment itself and immunization with a homogenate of the parasite stimulated a leucocytosis and protected against infection by E. multilocularis; carrageenan abrogated protection in PHA-treated animals. The results of this study confirm that protection against echinococcosis can be induced non-specifically; these results suggest that immunity in hydatid disease may have an important component in the inflammatory reaction.

Animals↗
PubMed1983

Leukocyte subset analysis and related immunological findings in acquired immunodeficiency disease syndrome (AIDS) and malignancies.

Cell surface marker analyses conducted on human peripheral blood lymphoid cells have proven extremely useful in the diagnosis of immunodeficiency and the diagnosis and staging of malignancies. In this paper we have focused on the ratio of helper to suppressor cells in patients with the acquired immune deficiency syndrome and in patients with malignancy. In thirty-three patients with the acquired immune deficiency syndrome, the majority showed an inverted helper:suppressor ratio, elevated serum thymosin alpha 1, and elevated serum lysozyme levels. The inverted ratio was due to a deficiency in T-helper cells. The inverted helper:suppressor ratio was associated with functional suppressor cell activity that was seen in 12 out of 21 patients examined. Patients' lymphocytes were found to suppress the PHA, pokeweed mitogen, and concanavalin-A responses of normal subjects' lymphocytes. The suppression also correlated with impaired lymphocyte proliferative responses among the patients' cells themselves. Because of these findings, the helper:suppressor ratio was studied in patients with solid tumors, lymphoma, acute leukemia, chronic lymphocytic leukemia, and hairy cell leukemia. Approximately 30% of these patients have an inverted helper:suppressor ratio. However, in ten out of 30 patients with chronic lymphocytic leukemia and in three out of 45 patients with lymphoma, the helper:suppressor ratio was elevated, being greater than 3.0. The significance of these findings is as yet to be explored, but it is suggested that an inverted helper:suppressor ratio in patients with malignancy may relate to an advanced stage of disease or a poor prognosis. Documentation of this point will require further study.

Acquired Immunodeficiency Syndrome↗