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Biomedical subjects

N Trainin

Publications and source records attributed to N Trainin.

At least 55 records · Page 3Linked to original sources
PubMed1986

Effect of oral colchicine on T cell subsets, monocytes and concanavalin A-induced suppressor cell function in asthmatic patients.

Asthmatic patients have a deficiency of concanavalin A-(Con A) induced suppressor cell function. We tested whether oral colchicine 0.5 mg twice daily for 7 days could correct this immunoregulatory abnormality. Peripheral blood mononuclear cells were incubated with Con A and then suppression of proliferation was measured by coculture of these cells with healthy volunteers' mononuclear cells and phytohaemagglutinin. Sixteen asthmatic patients had significantly (P less than 0.002) decreased Con A-induced suppressor cell function (17.0 +/- 17.2%, mean +/- s.d.) as compared to 13 healthy volunteers (37.9 +/- 14.9%). Oral colchicine significantly (P less than 0.05) increased, though only partially corrected, these 16 asthmatic patients' Con A-induced suppressor cell function (28.1 +/- 14.3%). Asthmatic patients had an increased number of monocytes (691 +/- 289 vs 388 +/- 271/mm3 for normals, P less than 0.01) and a normal number of lymphocytes, Leu 4+ total T cells, Leu 3+ helper/inducer T cells, and Leu 2+ suppressor/cytotoxic T cells as well as a normal Leu 3/Leu 2 ratio. Oral colchicine significantly (P less than 0.005) decreased the number of monocytes (451 +/- 255/mm3) without significantly affecting the number of lymphocytes, Leu 4+, Leu 3+, or Leu 2+ T cells, or the Leu 3/Leu 2 ratio. These results are consistent with the hypothesis that the deficiency of Con A-induced suppressor cell function in asthmatic patients may be due, in part, to an increased number and/or abnormal activity of monocytes. If so, then oral colchicine may have partially corrected the deficiency of Con A-induced suppressor cell function by decreasing the number and/or modulating the activity of monocytes.

Adult↗
PubMed1986

Cellular immune aspects of the human fetal-maternal relationship.

In the present study the number and the function of T lymphocytes obtained from peripheral blood of 35 mothers immediately after delivery and from the cord blood of the respective newborns were tested. Furthermore, the effect of the newborns' lymphocytes on the immunological competence of the mothers' lymphocytes was investigated by means of graft-versus-host-reaction xenograft test. The blood of 14 of the mothers and their newborns was also examined by monoclonal antibodies for determination of T helper and T suppressor lymphocytes. A marked reduction in the absolute number of T helper cells was found in the blood of mothers after delivery. In addition, mothers' lymphocytes manifested a high suppressor activity when added to normal human lymphocytes. It was also found that the cord blood contains lower number and percentage of T suppressor cells. Yet the T cells of the cord blood exert a high suppressor activity on the mother as well as on normal donor lymphocytes. The impaired function of cord blood lymphocytes could be impaired function of cord blood lymphocytes could be restored by in vitro addition of THF, a thymic hormone.

Female↗
PubMed1986

Cellular immunity in patients with acquired immunodeficiency syndrome (AIDS) in Israel: effects of THF, a thymic hormone in vitro.

Markers and functions of T cell subsets were studied in 3 Israeli males suffering from AIDS, two of whom were homosexuals and one heterosexual developing AIDS after a coronary bypass operation followed by multiple blood transfusions. Two healthy homosexual partners of one of the AIDS patients were also studied. Sera from these individuals were also tested for suppressive activity on control normal donor lymphocytes. Monitoring of T-cell subsets during a period of 3-12 months demonstrated a reversed T helper: T suppressor ratio in the 3 AIDS patients and in one of the healthy homosexuals. Addition of AIDS sera to normal T helper cells abolished the helper activity whereas its addition to normal isolated T suppressor cells enhanced the suppressor activity. Incubation of the patients lymphocytes with THF, a calf thymus hormone, restored the impaired helper cell activity. A suppressor factor unrelated to acid labile interferon was demonstrated in the sera of the AIDS patients but was not found in the sera of the healthy homosexuals. THF neutralized the suppressor effect of this serum factor when tested on normal lymphocytes.

Acquired Immunodeficiency Syndrome↗
PubMed1986

In vitro restoration by interleukin-2 (IL-2) of the impaired natural killer cell activities, IL-2 receptor expression, and T cell proliferation in hemophilia.

Five of 22 hemophiliacs who were seropositive for human T cell leukemia virus III (HTLV III) and manifested severe impairment of immune parameters (both in vivo and in vitro) similar to those observed in patients with clinical symptoms of acquired immune deficiency syndrome (AIDS) were chosen for this study. Profound lymphopenia was observed in four of five patients with decreased and qualitatively impaired helper/inducer (T4) cells and increased T suppressor/cytotoxic (T8) cells. Observed in all patients was impaired endogenous production of interleukin-2 (IL-2), expression of the IL-2 receptor combined with diminished responses to mitogens, mixed leukocytes reaction (MLR), and natural killer (NK) reactivity. In vitro supplement of exogenous IL-2 markedly augmented T and NK cell functions, as well as the expression of activation antigens on both T4 and T8 cell in four of five patients. Our findings suggest that a substantial proportion of this cell-mediated immunologic defect in hemophiliacs stems from their inability to produce adequate amounts of IL-2. Interleukin-2 may therefore have the potential for therapy as an immune response modifier in patients with hemophilia by providing beneficial preventive therapy for patients at risk.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Treatment of congenital immune deficiencies with a thymic hormone--thymic humoral factor.

Five infants with congenital immune defects are presented. Three had various combined immune deficiencies (CID) and two had thymic deficiencies only. As bone marrow or thymus transplantations were not feasible in these patients, we attempted treatment with thymic humoral factor (THF), a thymic hormone, by daily i.m. injections during biweekly courses. In one CID patient, a partial improvement in immune indices and temporary clinical improvement were achieved. In the other two, THF did not arrest the patients' demise. The two patients with thymic dysplasia benefitted repeatedly from THF treatment, as exemplified by the disappearance of wasting, diarrhea and infections and by reconstitution of T cell parameters. Nevertheless, the patients relapsed after prolonged periods without THF administration. We therefore propose the administration of long-term, continuous or intermittent thymic hormone replacement therapy in infants with congenital thymic defects. Early diagnosis and immediate institution of treatment will probably improve prognosis.

Female↗
PubMed1985

Thymus hormones do not induce proliferative ability or cytolytic function in PNA+ cortical thymocytes.

A variety of thymus hormone preparations, as well as drugs known to perturb cell differentiation, were tested for their ability to induce nonfunctional cortical thymocytes to become functional precursor cells. Murine cortical thymocytes, defined as the high peanut agglutinin (PNA) binding or as the low H-2K, major [86%] thymocyte subpopulation, were isolated by fluorescence-activated cell sorting. Their function was assessed in a high cloning efficiency, growth factor saturated, concanavalin A-stimulated limit-dilution culture system, determining the number of precursors of extended clones (PTL-p), or determining with a lectin-mediated tumor-lysis readout the number of precursors of cytolytic clones (CTL-p). The hormone preparations tested were crude or partially purified culture supernatants from thymus "epithelial" monolayers (TES), soluble extracts of thymic nonlymphoid tissue (STF), semipure thymus humoral factor (THF), and the pure peptides thymopoietin 32-36 (TP5) and "facteur thymique sérique" (FTS). These preparations were either added directly to the limit dilution cultures, or were first preincubated with the cells, which were then subjected to limit-dilution culture. In no case did the hormone preparations cause any increase in the level of PTL-p or CTL-p in the PNA+ or low H-2K thymocyte population, even though a conversion of only a few percent to functional cells could have been detected. Two possible explanations are considered. One is that the main function of these materials is to control post-thymic peripheral T cells, rather than to induce intrathymic differentiation. Another is that the typical cortical thymocyte is beyond the stage at which thymocytes can be induced by hormones, a view that is strengthened by the failure of either 5-azacytidine or the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate to activate these cells. In this latter explanation the true intrathymic target of hormone action may be an earlier, and very minor, thymus subpopulation.

Animals↗
PubMed1985

The influence of thymic humoral factor on systemic lupus erythematosus lymphocyte function.

The influence of thymic humoral factor, THF, on systemic lupus erythematosus, SLE, lymphocyte function was investigated. Increasing numbers of SLE T-cells, rosetted at 4 degrees C or 37 degrees C, were cultured with allogeneic normal B-cells and the change in IgM synthesis was assessed. Lymphocytes of some SLE patients showed improved suppression with THF when rosetted at 37 degrees C. Normal control lymphocytes did not show a net change in suppression with THF. The subgroup of SLE patients that showed improved suppression with THF in vitro might be a more appropriate group for in vivo therapeutic trials with thymic hormone, TH, than SLE patients in general.

B-Lymphocytes↗
PubMed1985

A mouse ear reaction for assessment of human lymphocyte immunocompetence.

A mouse ear reaction for testing cell mediated immunity of human lymphocytes using the local graft-versus-host reaction assay is described. Five million human mononuclears were locally injected into the ears of immune suppressed NZW mice. The reaction mounted was quantitated by determining the 125I-Iodo-Deoxyuridine (125I-UdR) incorporation in both ears. The ratio of 125I-UdR incorporation, of the injected to that of the non-injected ear (GVHR index), 7 days after lymphocyte injection, served as an accurate measure for the extent of the reaction. Only normal human mononuclears and purified, separated normal human T lymphocytes mounted a local graft-versus-host reaction. Whereas normal human B lymphocytes, chronic lymphatic leukemia B lymphocytes, mononuclears from patients with transitional cell carcinoma of the bladder, irradiated normal human mononuclears, mouse syngeneic mononuclears, or human erythrocytes gave no positive reaction. These experiments demonstrate that this assay can be used to quantitate an in-vivo specific graft-versus-host reaction.

Animals↗
PubMed1985

In vitro induction of T-suppressor lymphocytes by THF, a thymic hormone, in psoriatic children.

T-lymphocyte number and function as well as the effect of a thymic hormone on the T-suppressor cell subset were studied in 22 children suffering from psoriasis vulgaris, subdivided into two groups, those with less than 20% of total skin area involved and those with more than 20% of involvement. The T-cell number was lower in the latter group than it was in the first group or in normal controls. There was no significant difference in the functional activity of T cells in the two groups of patients. The number of T-suppressor cells was significantly lower in the psoriatic children than in normal controls, being lowest in the children showing greater skin involvement. THF, a thymic hormone isolated from calves, was found in vitro to induce T-suppressor cells in the peripheral blood of the psoriatic children, suggesting that this hormone may be able to play a role in the treatment of this disease.

Adolescent↗
PubMed1985

Modulation of T-cell subsets in asthmatic children by THF, a thymic hormone.

Induction of theophylline-sensitive T-suppressor cells with THF, a thymic hormone, resulted in elevation of the low levels of these lymphocytes in non-treated asthmatic children. Evaluation, however, by monoclonal OKT8 antibodies did not show changes in the levels of the OKT8+ cells after THF incubation. In the treated asthmatic children, normal levels of theophylline-sensitive T-suppressor cells as well as OKT8+ cells were found. These normal levels were not changed with THF after in vitro incubation.

Adolescent↗
PubMed1984

Immune modulation of a T-suppressor cell lymphoma by thymic humoral factor, a thymic hormone.

Lymphoid cells obtained from a mediastinal mass and bone marrow as well as peripheral blood of a patient with poorly differentiated diffuse malignant lymphoma were found to have both E and complement receptors. Addition of the bone marrow lymphoblasts to normal human T-lymphocytes induced a suppression of normal T functional activity as measured by a local xenogeneic graft versus host reaction. Incubation of the same cells with thymic humoral factor (THF), a thymic hormone, reversed their functional activity from suppression to help. Control studies with normal T-suppressor lymphocytes also showed a reversal of function to helper activity upon incubation with THF. In studies of normal T-lymphocytes with monoclonal antibodies, incubation with THF induced no change in phenotype in either theophylline-sensitive (suppressor) cells or theophylline-resistant (helper) cells. The ability of THF to modulate helper and suppressor activities suggests that this or similar agents may provide a useful means of therapy for disorders of immunoregulation.

Adult↗
PubMed1984

Impaired immune regulation in children and adolescents with hemophilia and thalassemia in Israel.

The immune function was assessed in 22 children, adolescents and young adults with asymptomatic hemophilia, and 15 with thalassemia, in Israel. Five patients with hemophilia and two with thalassemia were found to be severely abnormal, having cutaneous anergy, very low T-helper cells, elevated T-suppressor cells, inverted T-helper/suppressor ratio, reduced response to mitogens and antigens, and nonfunctional NK cells. Four of the five hemophilia patients exhibited profound lymphopenia also. Decreased T-helper and mildly elevated T-suppressor cells with inverted T4/T8 ratio were observed in the hemophiliacs as a group. In the severe group, the reduction in T-helpers and T4/T8 ratio was more pronounced. The thalassemics as a group were found to have increased numbers of T-suppressor cells with decreased T-helper cells in those with intact spleen only. Both groups studied were found to have elevated IgG levels and low natural killer (NK) activity and normal response to mitogens. Cutaneous anergy was found to be a reliable indication for severe T-cell dysfunction and may serve as an early indication of impending AIDS. These results indicate that patients with hemophilia and with heavily hypertransfused thalassemia may be at increased risk of AIDS as they approach adolescence.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Immune derangements in asymptomatic male homosexuals in Israel: a pre-AIDS condition?

We have described several immune derangements found in a clinically asymptomatic group of 117 male homosexuals (MHS) in Israel. These consisted of a marked decrease in TH and TS cells, decreased NK and allogeneic response, and increased levels of acid labile alpha-interferon and circulating immune complexes (CIC). Most of these alterations were found in approximately 40% of the subjects, with no simple correlation between them. Since Israel is a low incidence area for AIDS and related syndromes, it is suggested that this situation reflects a common situation among asymptomatic MHS in general, although the reasons for these impairments are not clear. This situation may therefore explain susceptibility of the male homosexual for developing AIDS, given the appropriate circumstances, environment, and genetic background.

Acquired Immunodeficiency Syndrome↗
PubMed1984

The activities of enzymes of purine metabolism in murine thymus dependent lymphocytes.

Measurement of the activities of purine metabolizing enzymes in murine T cell subpopulations showed that these activities differed markedly among T cells of different levels of functional maturity. The activities of adenosine deaminase and deoxyadenosine phosphorylation were highest in immature, PNA + thymocytes, while the activities of purine nucleoside phosphorylase, ecto-5'-nucleotidase and deoxyguanosine phosphorylation were highest in mature, splenic T cells. These enzymes' activities can be used as biochemical markers for T cell of different degree of maturation.

5'-Nucleotidase↗
PubMed1984

Effect of colchicine on T cell subsets of healthy volunteers.

We examined the effect of oral colchicine (1-2 mg/day) on four healthy volunteers' T cell subsets. Colchicine significantly (P less than 0.01) decreased the mean (+/- SD) percent of OKT3+ total T cells (from 70 +/- 16 to 47 +/- 13), OKT4+ helper/inducer T cells (from 44 +/- 9 to 24 +/- 6), and OKT8+ suppressor/cytotoxic T cells (from 27 +/- 7 to 17 +/- 7), but did not significantly affect the OKT4:OKT8 ratio (from 1.64 +/- 0.21 to 1.48 +/- 0.45) or concanavalin A-induced suppressor cell function (from 44 +/- 9% to 47 +/- 13%). Thus, colchicine non-selectively decreased the circulating helper/inducer and suppressor/cytotoxic T cells.

Adult↗
PubMed1984

THF, a thymic hormone, promotes interleukin-2 production in intact and thymus-deprived mice.

T cells stimulated by mitogen or antigen produce a T cell mediator, interleukin-2 (IL-2), which induces clonal expansion of activated target cells. The activity of IL-2 obtained from cell-free supernatants of spleen cells after 24-h incubation with concanavalin A was tested in an IL-2-dependent blast cell proliferation assay. IL-2 production was found to be diminished in neonatally thymectomized (NTx) mice. Treatment of NTx mice with a series of 14 daily injections of thymic hormone, THF (5-10 ng), resulted in reconstitution of IL-2 activity to the level found in intact, untreated mice. The rise in IL-2 activity was observed to be part of a general reconstitution of the immune capacity in the THF-treated NTx mice, manifested by elevated responses to mitogenic stimulation by T lectins and elevated mixed lymphocyte reactivity and cell-mediated cytotoxicity. Elevation of IL-2 activity could also be detected in vitro when spleen cells from intact mice were preincubated with THF for 24 h. THF did not enhance the production of interleukin-1 (IL-1) by bone marrow-derived macrophages, and in experiments in which T cells and macrophages were separately exposed to THF, augmentation of IL-2 activity was found only when the T cell-enriched spleen fraction was pretreated with THF. This was taken as proof that THF acted exclusively on T cells capable of producing IL-2, and that neither macrophages nor IL-1 were involved in the T helper activity induced by THF. Although THF could induce and/or augment IL-2 production by helper T cells, THF lacked IL-1 and IL-2 characteristics, since it could not maintain IL-2-dependent clonal expansion of target blasts nor induce IL-2 production by activated T cells.

Animals↗
PubMed1984

A controlled trial of treatment of acquired immunodeficiency in severe measles with thymic humoral factor.

A randomized controlled trial of treatment with thymic humoral factor (THF) in 20 children with severe complicated acute measles infection, resulted in objective benefit as evidenced by improvement in the ESR and a fall in C-reactive protein, fewer complications and a reduced incidence of secondary herpes infection. An increased ratio of helper to suppressor T cells (OKT4/OKT8 ratio) and a greater lymphocyte transformation response to phytohaemagglutin was seen in those children receiving THF. We conclude that THF treatment helps to prevent the development of complications particularly secondary viral infections possibly by enhancing cell-mediated immune responses.

Child, Preschool↗