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Biomedical subjects

N Trainin

Publications and source records attributed to N Trainin.

At least 19 recordsLinked to original sources
PubMed1992

T lymphocyte subsets and function in the peripheral blood of patients with urological cancer.

The phenotypic distribution and immune reactivity of T lymphocyte subpopulations from peripheral blood of 50 patients with urological cancer were determined. Included were 36 patients with bladder transitional cell carcinoma, 7 patients with renal cell carcinoma and 7 patients with prostatic carcinoma. Thirty-eight age-matched patients with benign urological disease served as controls. A depression in immune competence was found in the group of male patients with infiltrating bladder cancer. In more than 50% of the patients with infiltrating bladder carcinoma, the T helper (CD4) subset was reduced with a concomitant inversion in the CD4/CD8 ratio and impairment in the T cell function as determined by the ability to proliferate upon phytohemagglutinin and concanavalin stimulation. Patients with superficial bladder carcinoma, as well as those with renal cell carcinoma had an immune profile similar to that of the control group. The group of patients with prostatic carcinoma had higher mean CD4/CD8 ratios than the control group, resulting from decreased suppressor/cytotoxic cells. Our results have indicated that the characterization of T cell subset and lymphocyte activity correlated well with the histopathologic state of patients with bladder carcinoma. Thus, the determination of the CD4/CD8 ratio may prove a valuable method for monitoring patients with bladder carcinoma, in addition to serial urine cytology, random urothelial biopsies and flow cytometry.

Adenocarcinoma↗
PubMed1992

Thymic humoral factor-gamma 2, an immunoregulatory peptide, enhances human hematopoietic progenitor cell growth.

Thymus humoral factor-gamma 2 (THF gamma 2), an octapeptide important for T-lymphocyte regulation, was assessed for its effect on the in vitro growth of human hematopoietic progenitor cells. This was achieved using a recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF)-stimulated myeloid cell colony formation (granulocyte-macrophage colony-forming cells, GM-CFC) assay as well as a recombinant erythropoietin (rEpo)-stimulated erythroid burst formation (erythroid burst-forming units, BFU-E) assay. Cells were obtained from bone marrow (BM) and peripheral blood (PB) of normal healthy donors and from patients with suppressed bone marrows. The latter group included aplastic anemia, leukemia, and lymphoma patients and patients with solid tumors who responded to intensive chemotherapy with significant pancytopenia. THF gamma 2 significantly enhanced normal BM and PB GM-CFC and PB BFU-E by 2- to 2.5-fold. This effect was totally dependent on the presence of the respective growth factors, that is, rGM-CSF or rEpo, and was specifically reversed by an anti-THF gamma 2 antiserum. Furthermore, although THF gamma 2-induced enhancement of GM-CFC colony formation was not affected by lymphocyte or monocyte depletion, the augmenting effect of the peptide on BFU-E was completely abrogated in the absence of lymphocytes. THF gamma 2-induced augmented growth of progenitor cells derived from severely suppressed marrows was minimal. However, cells from moderately neutropenic patients with leukemia in remission or with lymphoma under chemotherapy responded to the peptide similarly to cells from normal donors. These results suggest a stimulatory role for THF gamma 2 on human myeloid and erythroid hematopoietic progenitor cells. They also suggest the lymphocyte dependence of BFU-E enhancement and lymphocyte independence of GM-CFC stimulation by THF gamma 2. In the former case the thymus-derived peptide may act through the induction of certain erythroid-enhancing lymphokines.

Adjuvants, Immunologic↗
PubMed1991

Thymic function.

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Hematopoiesis↗
PubMed1991

Hydrolysis of thymic humoral factor gamma 2 by neutral endopeptidase (EC 3.4.24.11).

A search for the natural substrates for neutral endopeptidase (NEP; EC 3.4.24.11) in the immune system led to investigation of the enzyme's action on thymic humoral factor gamma 2 (THF). The ectoenzyme rapidly and efficiently hydrolyses the Lys6-Phe7 bond of the octapeptide. The site of cleavage was confirmed by h.p.l.c. analysis, amino acid analysis and sequence determination of the products. Phosphoramidon (3.6 microM), a potent inhibitor of the enzyme, prevents this cleavage even during prolonged incubation. The high efficiency of hydrolysis of THF by NEP is similar to that reported for [Leu5]enkephalin, and the dipeptide Phe-Leu is the C-terminal product in the hydrolysis of both peptides. The presence of NEP, reportedly identified as the common acute lymphoblastic leukaemia antigen (CALLA), in bone-marrow cells and other cells of the immune system raises the possibility that it may play a role in modulating the activity of peptides such as THF.

Amino Acid Sequence↗
PubMed1991

Therapeutic effectiveness against MOPC-315 plasmacytoma of low or high doses of the synthetic thymic hormone THF-gamma 2 in combination with an "immunomodulating" or a "non-immunomodulating" drug.

We reported previously that treatment of mice bearing MOPC-315 plasmacytoma with the drugs L-PAM (phenylalanine mustard) or 5-FU (5-fluorouracil), in combination with low doses of THF-gamma 2, was more effective in increasing their survival time than treatment with the drug alone. We show here that in the combined treatment using a single injection of 5-FU followed by multiple (8-15) injections of THF-gamma 2, the megadoses were more effective than the low doses in increasing the survival time of MOPC-315 tumor-bearing mice. On the other hand, in combination with L-PAM, both low and high doses of THF-gamma 2 were equally effective. The need for high doses of THF-gamma 2, when used in combination with 5-FU, could be due to the fact that 5-FU acts as a "non-immunomodulating" drug and has to be used at a high, immunosuppressive dose.

Animals↗
PubMed1991

Characterization of peripheral blood T-cell subpopulation of bladder cancer patients.

The levels of immune reactivity of peripheral and blood T-lymphocytes were evaluated in 37 bladder cancer patients and 31 age-matched controls. T-lymphocyte subsets were quantified by monoclonal antibodies, and the immune reactivity was measured using stimulation with phytohemagglutinin (PHA), concanavalin A (ConA), and pokeweed mitogen (PWM). Comparing the patients before and after treatment revealed significant changes in the stimulation index of proliferative response to PHA, PWM, in the PWM% (the patient response compared to the control), and in the percent of T8 cells from the total count of blood lymphocytes. Further significant differences were found among the disease stages in the numbers of T3, T4 lymphocytes subpopulations and the total lymphocyte count. A significant interaction was found between the treatment and patient's sex regarding the T4:T8 ratio. Also, a higher prevalence of T4:T8 less than 1 was found among the patients compared to the controls before and after treatment regardless of the disease stage. This T4:T8 less than 1 ratio can serve as an indicator of immune competence in bladder transitional cell carcinoma patients.

Aged↗
PubMed1990

A synthetic thymic hormone, THF-gamma 2, repairs immunodeficiency of mice cured of plasmacytoma by melphalan.

BALB/c mice cured of large MOPC-315 plasmacytomas by melphalan remain deficient in their spleen T-cell functions. This was manifested by impairment of the allogeneic and the antibody responses in vitro to SRBC and in decreased numbers of T-cells including their subsets CD4 and CD8. IL-2 production and specific cytotoxicity against MOPC-315 tumor cells were, on the other hand, maintained. Treatment of these cured mice by in-vivo administration of THF-gamma 2, an octapeptide from calf thymus, repaired these deficits. This was evidenced by in vitro tests with spleen cells which manifested an increased allogeneic response and elevated generation of primary antibody response, restoration of T-cell subpopulations to normal and an enhanced IL-2 production above normal levels. The potential use of THF-gamma 2 as supportive therapy in cancer treatment is suggested.

Animals↗
PubMed1990

Adjuvant systemic therapy.

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Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

[Primary and secondary prevention of cancer in Israel].

Prevention and early detection of cancer are basic for decreasing cancer morbidity and improving survival rates. The Israel Cancer Association is active in the field of primary and secondary prevention of cancer and promotes a variety of projects in these fields.

Humans↗
PubMed1990

THF-gamma 2, a synthetic thymic hormone, increases effectiveness of combined chemotherapy and immunotherapy against RPC-5 murine plasmacytoma.

The effect of a synthetic thymic hormone, THF-gamma 2, on the anti-tumor activity of spleen cells was studied in mice immunized against the RPC-5 tumor. Following two courses of the THF-gamma 2 treatment, the mean RPC-5 specific cytotoxic response of immune spleen cells was significantly increased when compared to normal cells (P less than 0.001) and to untreated immune spleen cells (P less than 0.04). In addition, THF-gamma 2 treatment improved the competence of immune spleen cells in adoptive immunotherapy (AIT) when performed in combination with chemotherapy by melphalan. Recipients of spleen cells from THF-gamma 2 treated mice showed a 35% increase in survival when compared to AIT with immune cells alone. The results suggest that THF-gamma 2 treatment of donors for AIT might be applicable to cancer therapy in humans.

Animals↗
PubMed1990

Therapy of a fatal murine cytomegalovirus infection with thymic humoral factor (THF-gamma 2) treated immune spleen cells.

Infection of mice with murine cytomegalovirus (CMV) presents a model for the study of the role of the immune system in the pathogenesis of human CMV. We performed adoptive transfer experiments to evaluate the prospects for enhancing the anti-viral potential of murine CMV immune spleen cells by THF-gamma 2. Adult BALB/c mice resistant to murine CMV become highly susceptible following immunosuppression by cyclophosphamide. Recipient mice were injected with murine CMV and cyclophosphamide concomitantly, and 24 h later adoptive transfers of syngeneic immune spleen cells were performed. We showed that passive transfers of murine CMV immune spleen cells prevented the development of a fatal disease in 38% of the recipient mice. Daily injections of murine CMV immune donor mice with THF-gamma 2 enhanced considerably (93%) the therapeutic potential of virus-specific immune cells. These experiments provide direct evidence for the antiviral capacity of THF-gamma 2 through its immunomodulatory effect on immune T cells.

Animals↗
PubMed1990

Nonspecific immunopotentiators and pregnancy loss: complete Freund adjuvant reverses high fetal resorption rate in CBA x DBA/2 mouse combination.

CBA/J female mice mated with DBA/2J males show a high incidence of fetal resorptions. This paper presents data demonstrating that nonspecific immunopotentiation by complete Freund adjuvant (CFA) reversed pregnancy loss in CBA/J mothers. Immunization of more than 70 CBA/J females mated with DBA/2J males with CFA reduced the incidence of fetal resorption from 27.3 +/- 1.9 to 7.9 +/- 1.5%. The injection of Thymus Humoral Factor known to be a potent T cell stimulator did not reduce the number of fetal resorptions. The route of CFA distribution was found to be important--only foot pad injections were effective in fetal protection, whereas i.p. treatment did not reduce fetal resorptions. Fetal protection could be transferred by splenocytes of CFA-injected CBA/J mothers (9.6 +/- 5.0% fetal resorptions). Sera from treated CBA/J mice could not cause such an effect (17.6 +/- 4.6 vs. 21.3 +/- 6.1 in control animals). Thus, stimulation of the maternal immune system by nonspecific immunopotentiators can improve reproductive performance of this mouse combination which has an increased rate of pregnancy loss. Possible mechanisms of this fetal protection are discussed.

Animals↗
PubMed1990

Immune modulation exerted by thymic humoral factor (THF-gamma 2), on T-cell subsets and IL-2 production of umbilical cord blood lymphocytes.

The effect of a synthetic thymic humoral factor, THF-gamma 2, on the immune competence of T-cells was investigated in vitro on lymphocytes from human cord blood (UCBL). It was found that preincubation of UCBL with THF-gamma 2 caused an increase in the percentage of cells expressing the CD4 or the CD8 differentiation antigens, but did not affect the percentage of CD3 cells. The effect of THF-gamma 2 on PHA-induced IL-2 secretion was also studied and found that a 3hr preincubation with THF-gamma 2, prior to suboptimal PHA stimulation caused an increase in the IL-2 activity of the treated UCBL cultures. This effect was THF-gamma 2 dose dependent with an optimum in the range of 300-600 ng/ml and was not influenced by irradiation of the UCBL. These results indicate that THF-gamma 2, a synthetic octapeptide, modulates the immune state and response of human umbilical cord blood lymphocytes.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1990

Absence of T cell impairments in a unique group of anal-receptive transvestite and male prostitutes in Israel.

High rates of immunologic abnormalities in asymptomatic, clinically healthy urban homosexual men have been associated with promiscuous, unprotected receptive rectal intercourse, and related to infection by the human immunodeficiency virus (HIV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In cohort studies in Israel, which is still a low risk country for HIV infection and AIDS, about 40% of asymptomatic, clinically healthy male homosexuals consistently showed T cell defects that were not correlated with anal-receptive sexual behavior and were independent of HIV antibody status. Since pre-existing immune impairments in HIV-seronegative individuals have been implicated as a risk factor for seroconversion, we have attempted to investigate more precisely the role of anal-receptive homosexual activity as a risk factor for the acquisition of immune defects. We compared T lymphocyte profiles and mean geometric titers of EBV and CMV in a homogeneous group of 14 transvestite and male anal-receptive homosexual prostitutes with those of 77 HIV-seronegative male homosexuals who were not exclusively anally passive with multiple sex partners. While 44% of the control group showed a decrease of total T cells or their subpopulations as compared with normal heterosexual men (P less than 0.001), T lymphocyte values of the anal-receptive prostitutes were within the normal range. In the prostitutes, serum antibodies to HIV were detected in only 1 individual, to CMV in 12 of 13, and to EBV in all. Despite high mean geometric titers of antibodies to CMV (86.6) and EBV (25.8), frequent anal-receptive intercourse was not sufficient, in itself, to cause immune impairment in this unique group. The results suggest that the problem of cofactors contributing to immune deficiency in male homosexuals should be reexamined in countries with a low incidence for HIV seropositivity and AIDS.

Adolescent↗
PubMed1990

Selective accumulation of lymphocyte precursor cells mediated by stromal cells of hemopoietic origin.

Thymocytes were propagated in long-term cultures supported by stromal cells of both bone marrow and thymus origin. Interleukin 2 (IL-2) supplementation augmented the cell yield and allowed detailed phenotype analysis. Within 2-3 months of culture a cell population was selected in which the expression of Thy-1 antigen persisted, CD4 and CD8 antigens gradually declined, and Pgp-1 antigen, found on less than 5% of fresh thymocytes, was strongly increased. This cultured cell population (Thy-1.2 origin) contained no detectable spleen colony-forming units (CFU-S) but efficiently repopulated the thymus of Thy-1.1-irradiated congenic mice, indicating the precursor T-cell nature of the population. Upon removal from the stroma, the T cells exhibited poor cytotoxicity towards syngeneic tumor cells. Further propagation with IL-2 in the absence of stroma resulted in the acquisition of cytotoxic ability. Replacement of the horse serum used in the above experiments with fetal calf serum resulted in accumulation of cells expressing B220 antigen. This experimental model provides the means to maintain lymphocyte precursor cells in long-term culture and to further study their differentiation in the absence of stroma, both in vitro and in vivo.

Animals↗
PubMed1990

Prospects of AIDS therapy by thymic humoral factor, a thymic hormone.

Research performed in our laboratory has established that thymic humoral factor (THF), a peptide hormone isolated from calf thymus, leads to clonal expansion, differentiation and maturation of T-cell lymphocytes. THF augments the response to T-cell lectins, mixed lymphocyte reactions, graft-versus-host reactivity, antibody response to SRBC, cytotoxic responses and production of interleukin-2. Clinical data based on the use of THF of natural sources in about 200 patients indicate that it regulates differentiation of T-cell precursors, leading to normalization of the ratio between helper and suppressor/cytotoxic subsets. THF reconstitutes the defective cell-mediated immunity in patients affected by various types of neoplasms and suffering from secondary immune deficiencies, as a result of chemo and/or radiotherapy. THF-gamma 2 was purified and synthesized and found to be an octapeptide which retains all the biological activity of the thymus extracts. It is presently available for extensive clinical use.

Acquired Immunodeficiency Syndrome↗