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Biomedical subjects

F Hirsch

Publications and source records attributed to F Hirsch.

At least 73 records · Page 4Linked to original sources
PubMed1986

Production and characterization of a monoclonal islet cell surface autoantibody from the BB rat.

Islet cell surface autoantibodies are present in the serum of the spontaneously diabetic BB rat. The availability in large quantities of such autoantibodies should help us understand their significance in vivo. Fusions between BB rat lymphocytes and rat myeloma cells were screened by cellular enzyme linked immunosorbent assay and indirect immunofluorescence on rat living cells. They resulted in a stable hybridoma, called IC2, secreting a monoclonal immunoglobulin M specific for the surface of rat islet cells. This monoclonal antibody was found to bind to the surface of 56% normal rat islet cells and 72% rat insulinoma cells. Protease treatment of rat islet cells resulted in a subsequent 72-100% binding inhibition of IC2 to the surface of these cells, suggesting that IC2 specific antigen is a protein.

Animals↗
PubMed1986

Comparison of characteristics of human small cell carcinoma of the lung in patients, in vitro and transplanted into nude mice.

Specimens from 24 patients with metastatic small cell carcinoma of the lung were explanted in vitro as well as transplanted directly into nude mice. A method to obtain fibroblast-free cultures is described. This method resulted in cell lines which could be grown for more than one year in 79% of the cases. Fifty-four % of the tumours could be established as serially transplantable tumours in nude mice. The tumours were characterized by histology, electron microscopy, DNA index, and cell cycle distribution. The in vitro cell lines were furthermore characterized by the plating efficiency and by doubling time. The macroscopic growth of the heterotransplanted tumours was ascribed to a transformed Gompertz function. The tumour cells preserved their light microscopic constitution of small cell carcinoma of the lung in the model systems. The heterogeneity of the original tumours was reflected in vitro and in nude mice and the model systems thus allows an expression of the inherent heterogeneity and instability. The panel of transplantable tumours and the in vitro cell lines offer the study of biology inclusive of tumour progression of SCCL.

Animals↗
PubMed1986

The acute-phase induction of alpha 2-macroglobulin in rat hepatocyte primary cultures: action of a hepatocyte-stimulating factor, triiodothyronine and dexamethasone.

During inflammation a number of liver-derived plasma proteins increases in concentration. In the rat these so-called acute-phase proteins are mainly proteinase inhibitors, such as alpha 1-proteinase inhibitor, alpha 1-acute-phase globulin and alpha 2-macroglobulin. At present, the mechanisms responsible for the enhanced synthesis of acute-phase proteins are poorly understood. Therefore, we have studied the induction of alpha 2-macroglobulin synthesis in rat hepatocyte primary cultures. Adrenaline, triiodothyronine, estradiol and progesterone were tested for their ability to stimulate alpha 2-macroglobulin synthesis. Only triiodothyronine induced alpha 2-macroglobulin synthesis markedly. However, the presence of dexamethasone was a prerequisite for alpha 2-macroglobulin induction indicating a permissive action of glucocorticoids. Besides glucocorticoids and triiodothyronine a non-dialyzable factor (HSF) derived from rat Kupffer cells or human peripheral blood monocytes was found to be able to stimulate alpha 2-macroglobulin synthesis in hepatocytes. Equal amounts of HSF activity were found in conditioned media from lipopolysaccharide-stimulated and unstimulated rat Kupffer cells as well as in human monocytes. Since the supernatants of unstimulated rat Kupffer cells or human monocytes did not exhibit interleukin 1 activity, HSF activity distinct from interleukin 1 must exist. No HSF activity was found in media conditioned by rat Kupffer cells which had been treated with dexamethasone. Hepatocyte primary cultures were incubated with [35S]methionine-labeled proteins secreted by rat Kupffer cells. A 30 kDa polypeptide was found to be bound to or internalized by rat hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Rat monoclonal antibodies. III. A simple method for facilitation of hybridoma cell growth in vivo.

Hybridoma cells that did not grow when injected subcutaneously or intraperitoneally in histocompatible or Rnu/Rnu rats were injected intravenously into histocompatible recipients. Eight of the 9 cell lines injected in this way grew in several organs of the recipient 3-7 weeks later. Hybridoma cells proliferated mainly in the liver. When the liver homogenate of these animals was injected intraperitoneally into histocompatible recipients, hybridoma cells grew readily giving rise to ascites containing the expected monoclonal antibody for 6 of the 9 cell lines.

Animals↗
PubMed1985

In vivo self-reactivity of mononuclear cells to T cells and macrophages exposed to HgCl2.

Mercuric chloride induces in Brown-Norway rats a polyclonal activation of B cells resulting in a lymphoproliferation and in the production of autoantibodies. Experiments were performed to test the role of cells modified by HgCl2 in the induction of B cell proliferation by using the popliteal lymph node assay. Spleen cells, T cells and peritoneal macrophages exposed in vivo or in vitro to HgCl2 induced a proliferation of T and B cells in the draining popliteal lymph node. Spleen cells from Lewis rats who received HgCl2 were ineffective. These data suggest that modified cells could trigger autologous lymphocyte subsets and be responsible for autoimmunity induced by HgCl2.

Animals↗
PubMed1984

Polyclonal IgE increase after HgCl2 injections in BN and LEW rats: a genetic analysis.

An autoimmune disease and a dramatic increase in total serum IgE concentration are observed in BN rats that are chronically injected with HgCl2. In contrast, LEW rats do not develop the characteristic glomerulonephritis and are very "low IgE responders". In this study, we examined the genetic control of total serum IgE increase after HgCl2 injection in F1 and F2 hybrids, in both backcrosses between LEW and BN rats, and in LEW.1N congenic rats. Genetic analysis was performed using peak IgE concentrations expressed as log microgram/ml. A high IgE phenotype was found to be dominant. Eighty-five percent of F2 variance was due to genetic factors (VG) while only 15% of this variance was caused by environmental factors (VE). From observations in F2 hybrids and backcrosses, estimations of additive variance (VA) and dominance variance (VD) were made following three different methods. Genetic control by about four loci is demonstrated. One of these genes is RT1-linked. This gene contributes to 25% of the phenotypic difference observed between BN and LEW rats. No correlation was found between the peak total IgE level and autoimmune disease based on IgG deposition in spleen and/or kidney.

Animals↗
PubMed1984

Production of monoclonal anti-glomerular basement membrane antibodies during autoimmune glomerulonephritis.

Monoclonal anti-glomerular basement membrane (GBM) antibodies were obtained by fusing spleen cells from Brown-Norway (BN) rats injected with mercuric chloride with IR 983 F, a nonsecreting rat myeloma cell line. These antibodies showed the same pattern of fixation on renal basement membranes by indirect immunofluorescence. One of them was developed. It reacted both in vivo and in vitro with GBM but failed to react with collagenase-digested GBM, laminin, and collagen IV. This monoclonal antibody which resembles the kidney acid eluate obtained from BN rats injected with mercuric chloride induced a weak and transient proteinuria when intravenously injected into normal BN rats.

Animals↗
PubMed1982

Polyclonal effect of HgCl2 in the rat, its possible role in an experimental autoimmune disease.

Mercuric chloride induces an autoimmune glomerulonephritis in Brown-Norway (BN) but not in Lewis (LEW) rats. Injection of HGCl2 into BN rats regularly produced a transient appearance of plaque-forming cells (PFC) of anti-2,4,6-trinitrophenyl and anti-sheep red blood cell specificity and circulating anti-single-stranded DNA antibodies. Addition of HgCl2 to spleen cell cultures from BN rats induced an increase in anti-trinitrophenyl PFC and reverse PFC. This effect was no longer observed when nylon wool column-depleted or anti-Thy-1 antiserum-treated spleen cells were cultured in the presence of HgCl1. These data suggest that HgCl2 acts as a polyclonal activator on spleen cells in BN rats, but not on isolated B lymphocytes. In contrast, no effect of HgCl2 on immunoglobulin production was observed in LEW rats. Since polyclonal activation and immune-type nephritis are both seen in BN but not in LEW rats, polyclonal activation may participate in the pathogenesis of the HgCl2-induced autoimmune disease of BN rats.

Animals↗
PubMed1982

Acute haemodynamic and hormonal effects of captopril are diminished by indomethacin.

1. The acute haemodynamic and hormonal effects of 100 mg of captopril (SQ 14.225) orally were tested in twelve healthy men in the sodium replete state before and after indomethacin pretreatment. 2. Without indomethacin, mean arterial blood pressure was reduced at 30 and 60 min after captopril (P less than 0.02). Heart rate did not change during the whole experiment. Although plasma renin activity (PRA) increased (P less than 0.002), plasma and urinary aldosterone and plasma 18-hydroxycorticosterone (18-OH-B) decreased after captopril (P less than 0.02). Prostaglandin (PG) E2, sodium and potassium excretion rates remained constant after captopril. 3. Under indomethacin pretreatment, the fall in mean arterial blood pressure was less than without indomethacin at 30 and 60 min after captopril (P less than 0.05). Heart rate was constantly lower than without indomethacin during the whole experiment (P less than 0.05). Indomethacin pretreatment decreased basal PGE2 excretion (P less than 0.02) and baseline PRA as well as the increase in PRA after captopril (P less than 0.05). Control mineralocorticoid levels were significantly lower than without indomethacin. In indomethacin-pretreated subjects, aldosterone did not further decrease after captopril, and 18-OH-B fell only slightly. 4. Without indomethacin pretreatment a significant, positive correlation was found between PRA values before captopril and the maximum decrease of mean arterial blood pressure after captopril. Under indomethacin pretreatment this correlation was no longer demonstrable. The results suggest that prostaglandins may contribute to the haemodynamic and hormonal actions of captopril.

18-Hydroxycorticosterone↗
PubMed1978

Peritoneoscopy in the staging of 190 patients with small-cell anaplastic carcinoma of the lung with special reference to subtyping.

Peritoneoscopy with liver biopsy was routinely done as a pretreatment staging procedure in 190 patients with small-cell anaplastic carcinoma of the lung. Subtyping of the patients according to the WHO classification included 28.3% with fusiform cell type (WHO II,1), 28.9% with polygonal cell type (WHO II,2), 41.5% with lymphocytelike cell type (WHO II,3) and 1.3% with mixed types (WHO II, 4). Liver metastases were found in 21% of the patients with adequate liver biopsy. In addition macroscopic signs of liver metastases were observed in 9%. No significant differences were observed among the histological subtypes. Liver function tests, such as alkaline phosphatase, LDH and GOT, were of little value in excluding liver metastases. On the other hand, 2 of 3 abnormal liver function tests were highly indicative of liver metastases. In patients with positive liver biopsy, 41% had liver metastases alone and 76% had no other evidence of distant metastatic disease if bone-marrow involvement identified with bone marrow examination is excluded as a staging procedure.

Adult↗
PubMed1978

Chemotherapy of advanced small-cell anaplastic carcinoma. Superiority of a four-drug combination to a three-drug combination.

A controlled clinical trial compared three-drug and four-drug combination chemotherapy in 109 patients with advanced small-cell anaplastic carcinoma of the lung. The combination of vincristine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), cyclophosphamide, and methotrexate was significantly superior to the combination of the last three drugs alone with regard to median survival (230 versus 176 days) (P less than 0.01) and to duration of response (186 versus 112 days) (P less than 0.01). Objective response occurred in 78% and 75%, respectively. No significant difference in these values was observed in the comparison of the three subtypes of small-cell anaplastic carcinoma using the World Health Organization classification.

Aged↗