Biomedical subjects

I Berczi

Publications and source records attributed to I Berczi.

At least 19 recordsLinked to original sources

PubMed1992

Neuro-hormonal host defence in endotoxin shock.

The sensitivity (LD100) of mice to lipopolysaccharide (LPS) endotoxin and to its toxic moiety, lipid A (LA), increased 500-fold after adrenalectomy (ADX). Inhibition of glucocorticoid synthesis in intact mice by metyrapone had a similar, though less dramatic, sensitizing effect to LPS. In ADX mice, the serum level of tumor necrosis factor-alpha (TNF) was 40-60 times higher than that in controls at 2 h after LPS/LA treatment. In intact mice the serum corticosterone level fell 1 h after lipid A injection to below detectable levels, which was followed by a brisk increase reaching the peak level of 48-50 micrograms/100 ml at 2 h. Both TNF production and the lethal effect of PLS/LA could be inhibited in ADX mice by glucocorticoid treatment. Plasma prolactin was increased significantly 1 h after endotoxin administration in both intact and ADX animals.

Adrenalectomy↗

PubMed1992

Endocrine control of the immunosuppressive activity of the submandibular gland.

Extracts of the submandibular gland (SMG) of rats contain fractions that stimulate the in vitro proliferation of Con A-treated lymphocytes. One of the stimulatory fractions was also shown to induce in vivo immunosuppression in rats and mice in several experimental models. Since many other biologically active factors of the SMG had been found to be hormone dependent, we investigated the effects on the immunosuppressive factor of hypophysectomy (Hx) and of hormonal reconstitution in male Fischer rats. Hx induced a marked atrophy of the SMG together with an almost complete disappearance of both the in vitro lymphocyte-stimulating activity and the in vivo immunosuppressive activity, the latter assayed with the contact sensitivity reaction in mice. The treatment of the Hx rats with pituitary hormones demonstrated that prolactin (PRL), thyroid stimulating hormone (TSH), and luteinizing hormone (LH) induced a significant reconstitution of these biological activities, growth hormone led to the recovery of the lymphocyte-stimulating activity but not of the immunosuppressive activity, while follicle-stimulating hormone, and adrenocorticotropic hormone did not induce any recovery of these biological activities. In view of the positive results obtained with TSH and LH further experiments were done to compare the effects of thyroid and sex hormones with those of PRL. The results demonstrated that testosterone and thyroid hormones induced significant recovery of the lymphocyte-stimulating and the immunosuppressive activity. The combination of these two hormones with PRL produced the most effective results. On the other hand, estrogens and progesterone had no significant effects. These results confirm the effectiveness of androgens and thyroid hormones in stimulating the production of biologically active factors by the SMG. Moreover, they demonstrate that PRL, a hormone not previously considered to increase the activity of the SMG, stimulates the production of immunoregulatory factors in Hx animals.

Adrenocorticotropic Hormone↗

PubMed1991

Development and characterization of ouabain-resistant human fusion partners.

The ouabain-resistant mutant cell lines, HOA-1 and HOA-20 were developed from WI-L2-729-HF2 by cloning with increasing concentration of ouabain. Both parent and mutant cell lines were resistant to base analogues, 6-thioguanine (6-TG) and 8-azaguanine (8-AG) to the level of 20 micrograms/ml in the culture medium. The parent cell line WI-L2-729-HF2 was highly sensitive to ouabain, whereas HOA-1 and HOA-20 were resistant to ouabain to the level of 1 microM and 20 microM, respectively. However, all the cell lines were sensitive to HAT-selective medium which is essential for hybrid selection after fusion. All three lymphoblastoid cell lines were positive for Epstein-Barr virus nuclear antigen (EBNA), secreted TNF-beta (lymphotoxin) without any external stimulation, secreted trace amounts of IgG(kappa), which was also present in their cytoplasm and had IgM(kappa) as surface bound immunoglobulin. They also expressed the CD20, CD71 (transferrin receptor) as surface antigens. In addition to these antigens, HOA-20 also expressed CD38 antigen. The karyotype analysis of these cell lines revealed modal chromosomal numbers ranging from 40 to 47. The HLA-A, -B and -C antigens expressed by WI-L2-729-HF2 and its mutants HOA-1 and HOA-20 were identical. Both the HOA-1 and HOA-20 mutants were found suitable for the generation of hybrids after fusion with EBV-transformed human B-lymphocytes.

Antibodies, Monoclonal↗

PubMed1991

Pituitary hormones regulate c-myc and DNA synthesis in lymphoid tissue.

Hypophysectomy of Fischer 344 rats of both sexes led to a rapid involution of the thymus and spleen which was associated with a profound decrease in spontaneous DNA synthesis in these organs. The proportion of B lymphocytes in the spleen, of T cells and their subsets (CD4+/CD8+) in spleen and thymus, and the histological structure of the involuted organs remained normal. Treatment of hypophysectomized animals with growth hormone (GH) or prolactin (PRL) stimulated the expression of the c-myc proto-oncogene and DNA synthesis and reversed the involution in these organs. Replacement doses of adrenocorticotrophic hormone, follicle-stimulating hormone, luteinizing hormone, or thyroid-stimulating hormone had no influence on thymus or spleen size and DNA synthesis. A rapid expression of c-myc was also observed in thymuses and spleens of intact rats after the injection of GH or PRL. In vitro physiological concentrations (2.5 ng/ml) of either ovine or rat PRL or GH stimulated the incorporation of [3H]thymidine by thymus and spleen cells. These results indicate that GH and PRL regulate lymphocyte growth. This regulatory role is likely to serve as the principal mechanism of immunoregulation by these hormones.

Animals↗

PubMed1991

Growth inhibition of murine mammary carcinoma by monoclonal IgE antibodies specific for the mammary tumor virus.

Two IgE-producing hybridomas were established from spleen cells of Balb/c mice, which had been immunized with mouse mammary tumor virus (MMTV). These IgE monoclonal antibodies (mAbs) reacted specifically with the major envelope glycoprotein (gp36) of MMTV, as established by the immunoblot assay and by passive cutaneous anaphylaxis. The effect of the IgE mAbs (produced by clone A8) on the growth of the MMTV-secreting mammary adenocarcinoma H2712 was investigated in syngeneic C3H/HeJ mice. The mice were inoculated s.c. with either 10(5) (approximately 100 x LD50) or 10(6) (approximately 1000 x LD50) tumor cells and received repeated i.p. injections of 25 micrograms anti-gp36 IgE mAbs at 4-day intervals for 8 weeks. This treatment prevented the development of subcutaneous tumors in 50% of the animals. Similar protection was observed when the tumor cells (10(5)/animal) were injected i.p. 4 days prior to the beginning of the i.p. treatment consisting of injections of 25 micrograms mAbs at 4-day intervals for 6 weeks. However, these mAbs did not protect C3H/HeJ mice against the MMTV-negative MA16/c carcinoma cells. Hence, these results support the view that IgE-mediated cytotoxic mechanisms may play an immunologically specific antitumor surveillance role and that laboratory-induced antitumor IgE mAbs have the potential of specific therapeutic agents for in vivo destruction of tumor cells.

Animals↗

PubMed1991

Establishment and characterization of hybrid rat mast cells.

Rat peritoneal mast cells (RPMC) and rat basophilic leukemia (RBL) cells are representative of connective tissue-type (CTMC) and mucosal-type (MMC) mast cells, respectively. Using polyethylene glycol, we have fused RPMC with 6-thioguanine resistant, HAT (hypoxanthine, aminopterin, thymidine) sensitive RBL-CA10.7 or RBL-CK2 cells, yielding several hybrid rat mast cell lines (HRMC). The hybridomas exhibited different size and cytoplasmic granularity when compared with parental cell lines. Analysis of both high (Fc epsilon RI) and low affinity (Fc epsilon RL) receptors for IgE revealed that the hybrid lines had more variable receptor patterns than the parent lines. Three hybridoma lines were chosen for further study. Differential histochemical staining with alcian blue and safranin O dyes indicated the hybrids to be predominantly of the MMC type: however, a few cells of one of these uncloned hybridomas were found to be of the CTMC type. Attempts to isolate the CTMC hybridomas yielded one culture which was predominantly of the CTMC phenotype and in a number of other cultures, cells were found expressing simultaneously both the CTMC and the MMC phenotype. After 3 weeks in culture, however, all hybridomas, including those which were cloned further, expressed only the MMC histochemical phenotype. This was found to correlate with the presence of rat mast cell protease II (RMCPII) and the absence of RMCPI in all hybridomas, as detected by Western blot analysis. In addition, the histamine content of all cells was significantly lower than that of the parent RPMC. Most hybrid mast cells expressed both Fc epsilon RI and Fc epsilon RL which in some cases exhibited significant variations in the Mr. These results indicate that somatic cell hybrids expressing the MMC and CTMC phenotype can be produced by the fusion of RBL and RPMC. The CTMC phenotype, however, is unstable, and possible reasons for this are discussed.

Animals↗

PubMed1991

Placental lactogen is a haemopoietic hormone.

The anaemia and thrombocytopenia of hypophysectomized (Hypox) rats could be corrected readily by daily treatment with human placental lactogen. Spontaneous DNA synthesis in the bone marrow of Hypox rats was grossly impaired, which was also normalized by placental lactogen. Human placental lactogen exerted a direct mitogenic effect on rat bone marrow cells in vitro. These results indicate that placental lactogen is a potent haemopoietic hormone.

Anemia↗

PubMed1991

Hypophysectomized rats depend on residual prolactin for survival.

Hypophysectomized (Hypox) female Fischer 344 rats had 10-20% lactogenic activity in their serum when compared to controls by the Nb2 lymphoma proliferation assay. If such animals were treated daily with a rabbit antirat PRL serum, their serum lactogenic activity diminished further; severe anemia and immunological anergy developed; and death occurred within 8 weeks. In contrast, untreated Hypox animals increased gradually their serum lactogenic activity, starting on the 7th week after pituitary removal, which rose up to 50% of control levels by week 9. Hypox animals showed normochromic normocytic anemia, a grossly reduced immunocompetence, decreased body, thymus, spleen, adrenal, and ovary weights, and decreased DNA and RNA synthesis in the thymus, spleen, and bone marrow. However, the condition of Hypox animals did not deteriorate further over the 9-week experimental period. All the hematological deficiencies and decrease in organ weights observed in Hypox rats were normalized after grafting with syngeneic pituitaries (SPG). These effects of SPG could be inhibited by additional treatment with antirat PRL serum. Treatment of Hypox animals with ovine PRL had a restoring effect similar to SPG, which was not inhibited by additional antirat PRL serum treatment. Rat and ovine PRL and GH and human placental lactogen all stimulated the incorporation of 3H-thymidine by rat bone marrow cells in vitro. These results indicate that PRL has a multiple trophic effect and is capable of maintaining vital bodily functions for long periods of time.

Anemia↗

PubMed1991

Prolactin deficiency in rheumatoid arthritis.

Prolactin and growth hormone were determined from the sera of 48 patients with rheumatoid arthritis (RA) and 23 controls by radioimmunoassay and by the Nb2 lymphoma proliferation bioassay. A highly significant deficiency was found in the bioactivity of circulating prolactin (PRL) in patients with RA, whereas immunoactive PRL was near normal. Only age matched male patients showed significantly lower serum PRL levels by radioimmunoassay. Patients with RA with anemia and high reticulocyte counts had bioactivity of PRL elevated and those with anemia and low reticulocyte counts had a decreased bioactivity of PRL when compared to patients without anemia. Prolactin isolated from the sera of 5 patients with RA showed decreased bioactivity in comparison with PRL separated from 5 sex matched controls. Serum factors capable of enhancing or inhibiting the response of Nb2 cells to ovine PRL were also discovered. Our results indicate that RA is associated with PRL deficiency.

Anemia↗

PubMed1989

Immunoregulation by neuroendocrine factors.

The influence of the pituitary gland and of steroid hormones on the lymphoid system was demonstrated experimentally over half a century ago. Observations indicating the possibility of behavioural modification of immunity were also made at about the same time. Although these initial observations were followed by numerous investigations, the lack of sufficient basic knowledge of the endocrine and immune systems and serious methodological difficulties led to contradictions from which no definite conclusions could be drawn. Thus, the idea of neurohormonal-immune interaction fell gradually into disrepute. The remarkable effect of corticosteroids and their analogues on the immune system was regarded as a pharmacological phenomenon, rather than a physiological mechanism. During the past decade, this area gradually again became one of the forefronts of biomedical investigation and recently a number of volumes have been published on the subject of neurohormonal-immune interactions. Because of space limitations, only a brief overview of the subject can be given below and the reader is referred to the cited literature for detailed information.

Animals↗

PubMed1989

Pituitary dependence of bone marrow function.

The anaemia, leucopenia, thrombocytopenia and impaired DNA and RNA synthesis in the bone marrow of hypophysectomized rats could be restored by syngeneic pituitary grafts placed under the kidney capsule, or by treatments with ovine or bovine prolactin or growth hormone. Treatment with ACTH, FSH, LH and TSH had no effect in this respect. These results indicate that bone marrow function is regulated by the pituitary gland.

Anemia↗

PubMed1988

Human--human hybridomas secreting lipid A reactive monoclonal antibodies.

Five human-human hybridoma cell lines secreting monoclonal antibodies (mAbs) against lipid A (LA) were produced by cell fusion of Epstein-Barr virus (EBV) transformed human peripheral blood lymphocytes and a human lymphoblastoid cell line KR-4. All these mAbs were isotyped as IgM(kappa) and reacted with lipopolysaccharides (LPS) and LA of various gram-negative bacteria. Whereas the binding of only four of the five mAbs to solid-phase LA was blocked by polymyxin-B sulphate, the mitogenic effect of LPS and LA on murine B lymphocytes was inhibited by all five mAbs. These results demonstrate that the human immune system recognizes at least two common epitopes in lipid A of various gram-negative bacteria.

Antibodies, Monoclonal↗

PubMed1987

Decreased bioactivity of circulating prolactin in patients with rheumatoid arthritis.

Growth hormone and prolactin (PRL) were measured by radio-immunoassay in sera of 36 patients with rheumatoid arthritis (24 females and 12 males) and of 50 normal blood donors (25 males and 25 females). The bioactivity of PRL was also determined for both groups, using the Nb2 rat lymphoma proliferation assay. Although no significant difference was found between serum PRL values of patients and controls when determined by radio-immunoassay, the bioactivity of PRL was significantly decreased in patients' sera, when compared to values obtained in age and sex-matched controls. This decreased PRL bioactivity could not be attributed to drug treatments administered to the patients examined.

Arthritis, Rheumatoid↗

PubMed1987

Production and characterization of human-human and human-mouse hybridomas secreting Rh(D)-specific monoclonal antibodies.

Human monoclonal antibodies specific for the Rh(D) antigen were produced by cell lines generated by the fusion of pooled Epstein-Barr virus (EBV)-transformed B-cell lines secreting Rh(D) antibodies with the murine myeloma cell line NS.1 or with the human lymphoblastoid cell line HOA.1. The selection of hybrids was achieved in RPMI 1640 medium containing HAT and ouabain. Higher fusion efficiency was obtained with the NS.1 cell line; however, the hybrids with HOA.1 exhibited a greater clonal stability. The products of four clones (three human-human and one human-mouse) that consistently secreted antibodies for over 11 months were tested for specificity with a panel of red cells of various Rh phenotypes. The supernatants of all four clones showed anti-Rh(D) specificity but failed to react with the red cell Du phenotypes categorized as DV(Dw+) and DVI. Two of the three human-human clones secreted IgM(lambda) and the third IgG(kappa). The human-mouse clone produced IgG(kappa) antibody.

Animals↗

PubMed1987

Oestrogen dependent suppression of mitogen response in rat lymphocytes.

Female Fischer rats have a significantly (P less than 0.01) lower response to mitogens (phytohaemagglutinin and pokeweed mitogen) in whole blood cultures, than do male. In vitro cultures were carried out in 96-well micro-test plates with 5% blood over a period of 64 h, with a pulse of [3H]thymidine at 48 h. Ovariectomy resulted in a significant (P less than 0.01) increase in mitogen response, raising it to the level of normal males. Orchidectomy caused a small, but consistent rise in response. Injection of oestradiol valerate (at 0.5 mg/week, to yield physiological levels) suppressed the response of gonadectomized animals of both sexes to the level of normal female rats. Testosterone oenanthate had little effect unless administered in conjunction with oestradiol valerate, when a much greater depression of response was noted. Suppressor cells, or suppressive serum factors, could not be detected in the blood of normal females or oestrogen-treated animals during in vitro mixing experiments. Although it required 3 weeks for the ovariectomized animals' response to rise to the level of normal males, only 3 days of oestradiol valerate treatment was necessary to suppress the response again. Whereas it seems clear that oestradiol is responsible for the suppressed response of female Fischer rats, its mechanism of action has not been revealed by our experiments.

Animals↗

PubMed1986

Effects of mycoplasma infection on Fc receptors for IgE of rat basophilic leukemia cells.

Earlier studies from this laboratory had shown that rat basophilic leukemia cells carry two major receptors for IgE, named R and H, and a third minor receptor, designated 71K. It is now apparent that 71K is induced by the action of Mycoplasma hyorhinis, a common contaminant of tissue cultures. This induction is reversible. Decontamination either in in vitro or in vivo leads to a disappearance of 71K and re-infection causes its reappearance. The 71K receptor appears to be induced by the action of the mycoplasma on a surface molecule, most likely R, present on the cells at the time of infection. When receptors are occupied by IgE, 71K induction is inhibited. Other effects of mycoplasma infection include the significant reduction in the expression of transferrin receptors and increased histamine content of infected cells.

Animals↗

PubMed1986

Immunomodulation by tamoxifen and pergolide.

Treatment of rats with tamoxifen citrate or pergolide mesylate was as effective in inhibiting antibody formation and contact sensitivity skin reactions as was hypophysectomy. The immunocompetence of tamoxifen citrate- and pergolide mesylate-suppressed animals could be fully restored by additional treatment with prolactin or growth hormone.

Animals↗

PubMed1985

Immunomodulation in rats by transplantable anterior pituitary tumors.

The effect on the immune response of the MtT/W5 (W5), MtT/W10 (W10) tumors of Wistar-Furth rats and of MtT/F4 (F4) tumor transplantable in Fischer 344 rats was examined. Antibody response to sheep red blood cells and contact sensitivity reactions to dinitrochlorobenzene (DNCB) were used as immune parameters. In intact rats the W5 tumor suppressed the antibody response as much as did hypophysectomy (Hypox). The antibody response of Hypox rats was marginally improved by this tumor. Contact sensitivity was not suppressed in intact animals and the poor reactivity of Hypox rats was reconstituted to normal levels by W5. Treatment with bromocriptine (BRC) had no influence on tumor growth or on the immune reactivity of tumor-bearing hosts. The W10 tumor suppressed antibody formation, but not contact sensitivity in intact animals; the antibody and the DNCB response of Hypox animals was reconstituted partially, by this tumor. BRC treatment of tumor-bearing animals mimicked the effect of Hypox in this system. The F4 tumor suppressed antibody formation in intact rats and did not reconstitute the reactivity of Hypox rats. The DNCB response was not influenced by this tumor in intact animals and it was partially reconstituted in Hypox rats. Again, the reactivity of BRC-treated animals was similar to that of Hypox tumor-bearing animals. These results indicate that pituitary tumors may alter the immune reactivity of their hosts significantly.

Adenoma↗