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Biomedical subjects

N Trainin

Publications and source records attributed to N Trainin.

At least 73 records · Page 4Linked to original sources
PubMed1983

Cell mediated immunity and effects of "thymic humoral factor" in 15 patients with SSPE.

Cell mediated immunity (CMI) in 15 patients with subacute sclerosing panencephalitis (SSPE) was assessed by E-rosette formation, leucocyte migration inhibition factor (LIF) production, and proliferative responses to mitogens. In eleven patients, one or more of these parameters were impaired. These defects varied among the different patients and no consistent or uniform pattern of immune deficiency could be demonstrated. Although no single patient had a generalized reduction of all the T-cell functions, a diminished percentage of E-rosetting cells was the most frequent abnormal parameter (7 out of 15 patients). There was no correlation between the clinical state of the patients and the immune defects. Thymic humoral factor (THF), a thymic hormone, reconstituted at least one CMI impaired function especially the reduced levels of E-rosette forming cells in 7 out of 9 patients. It seems unlikely that a generalized cell-mediated defect is the underlying cause of this disease, but immunomodulatory therapy should be considered in some selected cases.

Child↗
PubMed1983

In vitro induction of T suppressor lymphocytes in recipients of renal allografts by THF, a thymic hormone.

Lymphocyte subpopulations were determined in 13 patients, recipients of kidney allografts, 7 of them during an acute rejection episode (ARE). Monitoring of the T lymphocyte suppressor or T helper cells was performed by aid of the theophylline sensitivity test and the local xenogeneic graft-versus-host reaction (GVHR). An absence or a striking decrease of theophylline-sensitive T suppressor cells was found in all patients during ARE. Incubation of the lymphocytes of these patients with a thymic hormone, THF, raised the number of TS lymphocytes from nil or from a very low level to normal or above. The therapeutic use of THF in selected renal allograft recipients is proposed.

Acute Disease↗
PubMed1983

Effect of colchicine on immunoregulatory abnormalities in familial Mediterranean fever.

The effect of colchicine on immunoregulatory T lymphocytes in children with familial Mediterranean fever (FMF) was studied. Concanavalin A (Con A)-induced suppressor cell function was significantly (P less than 0.0001) decreased in five untreated FMF patients (15 +/- 3%, mean +/- s.e.) as compared to six age matched paediatric controls (46 +/- 3%) and eight healthy adults (49 +/- 4%). When the five untreated FMF patients' mononuclear cells were pre-incubated in vitro with Con A plus 10(-5) M colchicine, their suppressor cell function was significantly increased (52 +/- 10%, P less than 0.01). Similarly, oral colchicine treatment (0.5 mg twice daily) significantly (P = 0.02) increased the five FMF patients' Con A-induced suppressor cell function to levels (34 +/- 6%) that were not significantly (P greater than 0.05) different than the paediatric controls or the healthy adults. The percentage of OKT8+ cells (but not OKT3+ or OKT4+ cells) was significantly (P less than 0.0001) decreased in 10 untreated FMF patients (16.0 +/- 0.9) as compared to 10 paediatric controls (27.6 +/- 2) or 10 healthy adults (25.7 +/- 0.6). The 10 untreated FMF patients had a significant (P less than 0.002) increase in the OKT4/OKT8 ratio (2.41 +/- 0.13) as compared to 10 FMF patients treated with 0.5 mg twice daily of colchicine (1.81 +/- 0.08), 10 pediatric controls (1.47 +/- 0.2), or 10 healthy adults (1.78 +/- 0.11). Colchicine appears to have corrected the FMF patients' elevated OKT4/OKT8 ratio by both decreasing the percentage of OKT4+ cells and increasing (but only partially correcting) the percentage of OKT8+ cells. Thus FMF patients have a suppressor cell deficiency in which colchicine treatment corrects their deficiency of Con A-induced suppressor cell function and their elevated OKT4/OKT8 ratio. This raises the possibility that colchicine might be potentially useful as an immunomodulating drug in treating patients with autoimmune or allergic diseases associated with a suppressor cell deficiency.

Adolescent↗
PubMed1983

Characterization of thymocyte subpopulations by enzymatic markers.

The activities of ecto-5'-nucleotidase (E5N), deoxyadenosine kinase (dAK) and deoxyguanosine kinase (dGK), were determined in thymocyte subpopulations, separated by peanut agglutinin (PNA). The activity of dAK in the PNA+ (agglutinated by PNA) thymocyte subpopulation was 2.5-fold that in the PNA- subpopulation. The activities of E5N and of dKG were found to be higher in the PNA- than in the PNA+ subpopulation by 15- and 4-fold, respectively. The activity of these enzymes can therefore be utilized to characterize the thymocyte subpopulation. In addition, since PNA+ cells are considered to be young immature precursors of the PNA- thymocytes, the activity of these enzymes may serve also as markers for the degree of maturation of the T cells.

5'-Nucleotidase↗
PubMed1983

The effect of thymic humoral factor on intracellular lymphocyte cyclic AMP in alcoholic liver disease.

Intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) in resting peripheral blood mononuclear cells (PBM) were determined in patients with alcoholic hepatitis (AH), with compensated alcoholic cirrhosis, in alcoholic subjects without liver disease and in healthy controls. The effect of thymic humoral factor (THF), a polypeptide extract of the thymus, on T lymphocyte cAMP levels was also evaluated. Only PBM from patients with AH had significantly lower resting levels of cAMP when compared to the controls. The net increase in cAMP levels induced with THF were comparable for all patient and control groups. These findings indicate the presence of an immune dysfunction in patients with AH.

Cyclic AMP↗
PubMed1982

Selective decline in differentiating capacity of immunohemopoietic stem cells with aging.

Bone marrow (BM) from young (3 months) and old (24 months) C57BL/6J mice were tested for the total number of colony forming units, which remain unchanged with age. The BM from both groups was used to reconstitute syngeneic, lethally irradiated mice that were 3 months' old. The reconstituted mice were followed for a period of 12 months for their ability to generate cell-mediated responses in mixed lymphocytic cultures and cultures containing the T mitogens--concanavalin A and phytohemagglutinin. For the first 8 months, mice given BM from young or old mice responded to a similar degree. Later, cellular immune responses of the mice reconstituted with BM from old mice declined markedly compared to those reconstituted with BM from young mice, although there was no detectable difference between the two groups in the hematopoietic compartment.

Aging↗
PubMed1982

Differences in the activity of adenosine deaminase and of purine nucleoside phosphorylase and in the sensitivity to deoxypurine nucleosides between subpopulations of mouse thymocytes.

The activities of adenosine deaminase (ADA) and of purine nucleoside phosphorylase (PNP) were measured in thymocyte subpopulations separated by peanut agglutinin (PNA), in unseparated thymocytes, in lymph node and in spleen cells. The PNA+ thymocyte subpopulation exhibited the highest ADA activity of all cells studied. The lowest PNP activity was found in the PNA- subpopulation of thymocytes. PNA+ cells, moreover, exhibited a more intensive DNA synthesis than the PNA- cells, and a greater sensitivity to deoxyadenosine toxicity in the presence of erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA). The two thymocyte subpopulations exhibited a similar sensitivity to deoxyguanosine (dG) toxicity.

Adenine↗
PubMed1980

Cell-mediated immunity in patients with mycosis fungoides in clinical remission: effect of thymic humoral factor on the immunocompetence of the lymphocytes.

In 10 patients with mycosis fungoides (MF) who were in clinical remission following local treatment with nitrogen mustard, cell-mediated immunity was investigated by means of tests for lymphocytes, forming rosettes in the peripheral blood, and the graft-vs-host reaction as well as intradermal skin tests. The effect of thymic humoral factor (THF) on T lymphocytes with impaired immunecompetence was also investigated. The results provided evidence of various kinds of damage to the immunologic system in most of the patients. Of the 10 patients, 4 had low percentages of T cells. Eight of the 10 had a graft-vs.-host reaction which was weak or negative, and in 4 of these, the administration of THF to the lymphocytes induced an improvement in immunoreactivity. These results together with other recently reported data indicate that the determination of cell-mediated immunity in patients with MF may be of prognostic importance. Those patients whose T lymphocytes respond to treatment with THF are probably the best candidates for immunotherapy.

Adult↗
PubMed1980

Enhancement of growth of a radiation-induced lymphoma by T cells from normal mice.

The effect of lymphocytes from normal mice on the growth of a syngeneic, radiation-induced, T-cell-derived lymphoma was investigated. Thymus and spleen cells enhanced the growth of admixed lymphoma cells in a reproducible manner. Growth enhancement was manifested by the earlier appearance and higher final incidence of tumours. Lymphocytes also enhanced the growth of radiation-damaged lymphoma cells. The enhancing activity of spleen cells was predominantly a property of T cells, since it was abolished by treatment with anti-theta serum plus complement and significantly less in spleen cells of nude mice. Tumour-enhancing thymocytes seem to belong to the immature thymic subpopulation, as indicated by their binding to peanut agglutinin.

Animals↗
PubMed1980

B and T lymphocytes in lymphoproliferative diseases of the skin. Effect of a thymic hormone on the immunocompetence of T lymphocytes.

Cell-mediated immunity using the E-rosette technique, the graft-versus-host reaction and intradermal skin tests were investigated in two groups of patients, twenty-two with benign lymphoproliferative diseases of the skin (lymphocytic infiltration of the skin and lymphadenosis benigna cutis) and nine with malignant lymphoproliferative diseases (mycosis fungoides and lymphoma cutis). The effect of thymic hormone upon T lymphocytes which proved to have impaired functional capacity was investigated. Seventeen of the twenty-two patients with benign lymphoproliferative diseases were found to have intact cellular immunity whereas seven of the nine patients with malignant disease proved to be immunodeficient. The determination of immune competence may be of help in establishing the correct diagnosis in doubtful cases and might also be useful in the follow-up of these patients. The improvement in functional capacity of T lymphocytes resulting from their interaction with a thymic hormone indicates that it holds therapeutic promise.

Adult↗
PubMed1980

Regulatory action of THF on T-cell reactivity to mitogens.

The effect of in vivo treatment with THF (thymus humoral factor) on the response of mouse lymphocytes to mitogens was investigated. Different preparations of THF were tested by daily i.m. injections into normal mice. Spleen, peripheral lymph node and thymus cells were tested for reactivity to several mitogens at various intervals after initiation of treatment. Our results indicate that the administration of THF to normal mice causes an inhibitory trend in the response of spleen cells to T-cell mitogens. It was found that the response of spleen cells to phytohemagglutinin (PHA) and concanavalin A (Con A) was strongly depressed after 7 days of treatment with 50 micrograms of THF. This was followed by a recovery of the response to normal levels after 14 days of treatment. The response of spleen cells to lipopolysaccharide (LPS) a B-cell mitogen, did not change throughout 14 days of treatmnent with THF. Lymph node cells of THF-treated mice behaved qualitatively in a similar manner to spleen cells, while thymus cells from THF-treated mice showed a significantly increased response to Con A. In contrast to normal mice, the injection of THF into mice with an impaired reactivity to PHA, such as thymectomized mice and tumor-bearing mice, caused an augmentation of the mitogenic response of spleen cells. These results suggest that in vivo administration of THF causes regulatory changes in the lymphocyte reactivity to T-cell mitogens.

Animals↗
PubMed1980

The local xenogeneic graft-versus-host reaction as a clinical test for immunocompetence of human T lymphocytes.

Studies carried out in our laboratory during the years indicated that the local xenogeneic graft-versus-host reaction (GVHR) might serve as a useful clinical assay of the immunocompetence of human T lymphocytes. Additional studies were therefore carried out using purified populations of B, T and null cells as well as normal mononuclear cell populations, so as to determine the nature of the cells responsible for induction of the reaction and further delineate the factors capable of modifying this pattern of reactivity. Populations of T cells alone gave the largest reaction whereas both B cells from patients with chronic lymphatic leukemia and null cells from patients with acute lymphatic leukemia failed completely to induce a GVHR. The addition of anti-T-lymphocytic serum abolished the reaction, providing further proof of the role played by T lymphocytes. Thymic hormone (THF) was found to enhance the reaction when applied both in vivo and in vitro. The immunostimulatory agents transfer factor and levamisole also enhanced the GVHR obtained with normal mononuclear cells. Cytoxan was found to have an enhancing effect at low doses and an inhibiting effect at high doses. Trypsin also acted to abolish the GVHR. The combination of two populations of normal mononuclears always gave a larger GVHR, indicating allogeneic antigen stimulation. Depletion of the monocytes from the population of normal mononuclears resulted in a smaller reaction, providing further evidence that monocytes are required for T-lymphocyte antigen-induced reactivity. On the basis of these findings it is proposed that the local xenogeneic GVHR is a useful clinical test for the measurement of immunocompetence of T lymphocytes, for the differential diagnosis of leukemias and for the determination of the effectiveness of THF.

Animals↗