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Biomedical subjects

N Trainin

Publications and source records attributed to N Trainin.

At least 19 recordsLinked to original sources

Enhancement of tumor growth by peritoneal macrophages of normal and tumor-bearing mice.

The effect of peritoneal macrophages on tumor growth was investigated in an in vivo transfer assay (Winn test). A significant acceleration of tumor appearance was observed in animals injected with tumor cells together with peritoneal exudate cells (PEC) from normal mice, as compared to animals injected with tumor cells alone. Macrophages were shown to be the cells responsible for tumor enhancement. PEC from tumor-bearing mice also caused a strong tumor-enhancing effect in the Winn test. These results indicate that non-activated macrophages can enhance tumor growth in in vivo transfers and raise the question of whether a similar effect takes place in the primary host of a tumor.

Animals

Effect of thymic humoral factor on cellular immune factors of normal children and of pediatric patients with ataxia telangiectasia and Down's syndrome.

Cellular immune functions of nine Down's syndrome patients and of nine was Ataxia telangiectasia vs. nine normal children and nine cord bloods, were evaluated using in vitro assays of peripheral blood lymphocytes. The in vitro assays included E rosette formation, antilymphocytic cytotoxicity by an antithymic antiserum and leukocyte migration inhibition factor (LIF) production. The mitogens and antigens used were phytohemagglutinin, purified protein derivative, and monilia antigen. The effect of a thymic hormone (THF) on these parameters was evaluated and it was administered therapeutically to three Down's syndrome patients and to two patients with Ataxia telangiectasia. Most deficient T-cell functions were reversed to normal after incubation of the lymphocytes with THF, or after THF therapeutic administration. In two Down's syndrome cases, the clinical course was not altered by THF administration, while one seemed to benefit from it markedly. One of the Atactic patients recovered from a severe viral infection, while the other died from intractable bronchopneumonia.

Ataxia Telangiectasia

Role of thymic hormone (THF) and of a thymic plasma recirculating factor (TPRF) in the modulation of human lymphocyte response to PHA and Con A.

The results presented here point to the possibility that calf thymus extracts contain, in addition to the thymic hormone (THF), a second component: thymic plasma recirculating factor (TPRF). THF, which is involved in the process of T cell maturation and has been characterized as a protein of m.w. 3000 eluted in the void volume of a G-10 Sephadex column (G-10-I), caused an increased level of intracellular cAMP in umbilical cord blood lymphocytes (UCBL). This is in agreement with our previous observation that THF plays a major role in the differentiation of T cells. The second active material, TPRF, also isolated from thymic extract, is of a molecular size below 500 and was eluted in a G-10 Sephadex column at the fourth protein peak; it seems to circulate in the blood. Previously, we had observed in impaired response of UCBL to PHA and Con A stimulation in the presence of dialyzed human plasma (DHP). Our present results indicate that this impaired response is restored exclusively by TPRF. A factor with TPRF-like activity was also isolated from the plasma of normal donors; yet it was not detected in the plasma of thymectomized patients suffering from myasthenia gravis (MG). This suggests that TPRF from plasma is thymus dependent. TPRF does not affect the level of intracellular cAMP in UCBL.

Concanavalin A

Role of L-alanine in the response of human lymphocytes to PHA and Con A.

The response of umbilical cord blood lymphocytes (UCBL) to PHA and Con A is strongly dependent upon the presence of dialyzable plasma components. The impaired response of human cells in the presence of dialyzed human plasma was restored by calf thymus extract. In the present experiments we have further purified calf thymus extract by means of paper electrophoresis and chromatography on thin-layer cellulose plates. We reached the conclusion that the active material in this model is a single amino acid, alanine. When the different isomeric forms of alanine were tested, we found that L-alanine is the only biologically active material. In addition, we have observed here that the allogeneic response of UCBL is also dependent upon the presence of dialyzable plasma components. This impaired allogeneic response of UCBL in the presence of DHP was restored by addition of L-alanine. The present findings suggest that, under in vitro conditions, for human cells to respond to mitogenic or allogeneic stimulation L-alanine is essential.

Alanine

Enrichment of in vitro and in vivo immunologic activity of purified fractions of calf thymic hormone.

Thymus humoral factor (THF), a thymus hormone which participates in the processes leading to acquisition of immunocompetence of lymphoid cells has been isolated in our laboratory by a stepwise gel filtration through various Sephadex columns. THF so isolated appears to be a polypeptide of 3,000 mol wt which contains approximately 30 amino acid residues. Here we have tested the biological activity of THF fractions of successive degrees of purity upon lymphoid cells from both intact and neonatally thymectomized mice. The lymphoid cell populations were treated with the various THF fractions by in vitro incubation for a short time and by repeated injection in vivo. The treated cells evidenced increased ability to react in the graft-versus-host assay in vivo and in mixed lymphocyte cultures in vitro concomitantly with the rise of intracellular cAMP. On the other hand no activity whatsoever was shown by any of the control materials tested. These bioassays permitted isolation of fractions progressively more active than the original crude dialyzate of thymus extract tested. Thus the active peptide component of THF eluted from DEAE Sephadex A-25 column was estimated to be 2 X 10(4)-fold more active than the crude dialyzate of thymus extract which served as a starting material.

Amino Acid Sequence

Immunological profile in sarcoidosis patients. The in vitro and in vivo effect of thymic humoral factor.

A study was made of the lymphocytes obtained from 25 patients suffering from sarcoidosis as proved by the Kveim-Siltzbach test and/or organ biopsy. The number of T lymphocytes was determined by the E rosette technique and functional activity by a local xenogeneic graft-versus-host reaction (GVHR) as well as skin tests with PPD, SK-SD, Candida and Trichophyton. In most cases the absolute number of T cells was low and there was an evident impairment of their functional activity. There was also a clear correlation between the severity of impairment of cell-mediated immunity and the clinical stage and activity of the disease. In vitro incubation of the lymphocytes with thymic humoral factor resulted in recovery of the functional activity of the T lymphocytes of 4 of the 7 patients tested, with the previously negative GVHR becoming positive. One of these patients was treated with thymic humoral factor with a resulting restoration of the cell-mediated immune response although there was no evident clinical improvement.

Graft vs Host Reaction

Thymic humoral factor in the assessment of T lymphocytics in a patient with T cell chronic lymphocyte leukemia.

Peripheral blood lymphocytes from a patient with T cell chronic lymphocytic leukemia were examined by a combination of cell markers (E and M rosettes, and surface Ig), the graft-vs.-host reaction, thymic humoral factor (THF) and scanning electron microscopy. It was not possible, at first, to determine by conventional methods whether the leukemic cells were of the B or T type, but the THF and graft-vs.-host reaction showed that T cell precursors were present. These cells were incompetent immature T cells that underwent maturation following treatment with THF. Three months later, the T cell nature of the disease was clearly demonstrated by the E rosette technique, although at this time the cells were no longer influenced by THF.

Female

Syngeneic GvH induced in popliteal lymph nodes by spleen cells of old C57BL/6 mice.

The frequency of autoimmune processes seems to increase with age. We have studied here whether lymphoid cells of aged mice have the potential to express autoreactivity by the use of the in vivo graft-vs-host (GvH) assay. It was found that spleen cells from old (104 weeks) C57BL mice caused significant enlargement of the popliteal lymph node upon injection into the footpads of syngeneic young or old recipients. Histologically this enlargement presented characteristics of a GvH reaction. This effect, which was not abolished by irradiation of the hosts, was totally cancelled by in vitro irradiation or by anti-theta treatment of the donor cells. These results indicate that T cells from aged mice have the potential to manifest autoimmune reactivity.

Aging

The in vitro effect of thymic humoral factor and levamisole on peripheral blood lymphocytes in systemic lupus erythematosus patients.

The in vitro effect of thymic humoral factor (THF) and levamisole on E rosette-forming cells in the peripheral blood of seventeen patients with systemic lupus erythematosus (SLE) was studied. Patients with active disease showed a low number of E rosette-forming cells. A significant rise in the number of E rosettes was obtained after incubation with both THF and levamisole. No such effect was observed on lymphocytes from patients with inactive disease and normal controls. In seven patients, three with active disease and four with well-controlled disease, short-term cultures were performed. The effect of THF on E rosettes was found to be the same before and after the short-term cultures. Possible mechanisms, by which THF (on the one hand) and levamisole (on the other) may increase the number of E rosettes in vitro, are discussed.

Adult