Effects of benzamidine derivatives on Ha-ras-1 mRNA accumulation in a Chinese hamster cell line transformed with the activated human T24 Ha-ras-1 oncogene.

Tetra benzamidine derivatives were found to inhibit proteinase activity, cell proliferation and accumulation of the Ha-ras-1 mRNA in the FHO6T1-1 Chinese Hamster cell line, transformed with the activated human T24-Ha-ras-1 oncogene. Di- and Tri-benzamidine derivatives were also found to be potent inhibitors of proliferation of FHO6T1-1 cells. These latter compounds could be proposed as useful substrates in the synthesis of drug-conjugated monoclonal antibodies or growth factors.

A randomized, double-blind trial of a gonadotropin releasing-hormone agonist (leuprolide) with or without medroxyprogesterone acetate in the treatment of leiomyomata uteri.

A randomized, double-blind study was performed on 16 women to compare the efficacy of daily subcutaneous (SC) injections of leuprolide acetate (LA; TAP Pharmaceuticals, North Chicago, IL) plus oral placebo tablets (group A, n = 7) with SC LA plus oral medroxyprogesterone acetate (The Upjohn Company, Kalamazoo, MI; group B, n = 9) in the treatment of leiomyomata uteri. Patients in group A had a significant reduction in uterine size from a pretreatment volume of 601 +/- 62 cm3 (mean +/- standard error) to a mean uterine volume of 294 +/- 46 cm3 at 24 weeks of therapy (P less than 0.01).

CG Dinucleotides of class II MHC genes are mutation hot-spots.

DNA methylation of human class II genes of the Major Histocompatibility Complex (MHC) was correlated with gene expression and methyl-related CG → TG and CG → CA changes. It was found that cytosine methylation of the CG dinucleotides of MHC class II genes should be involved in generating a fraction of nucleotide polymorphism, rather than in controlling transcription.

A 119Sn Mössbauer spectroscopic study on the interaction of dimethyltin (IV) derivatives with rat hemoglobin, and of related model systems in aqueous solution.

In the context of a study of the molecular basis of the antileukemia (murine) activity of diorganotin (IV) compounds, the interaction with rat hemoglobin (selected as a model protein) of the representative terms dimethyltin dichloride, dimethyltin glycylglycinate (Me2SnGlyGly), and dimethyltin L-cysteinate (Me2Sn-Cys) has been investigated by 119Sn Mössbauer spectroscopy. In order to possibly determine the reaction pathway, aqueous model systems in Hepes buffer at pH 7.4 were also considered.

Differential effects of benzamidine derivatives on the expression of c-myc and HLA-DR alpha genes in a human B-lymphoid tumor cell line.

In this paper, we report the effects of aromatic tetra amidines (TAPP-H) on cell growth and gene expression of a B-lymphoid human tumor cell line, WI-L2. The results obtained give evidence (a) for inhibition of cell proliferation by TAPP-H; (b) for stronger antiproliferative activity of TAPP-halo derivatives; (c) for TAPP-mediated inhibition of accumulation of c-myc RNA sequences but not of HLA-DR alpha mRNA and DR antigens. These results suggest that this class of antiproliferative compounds exhibit differential effects on cell-cycle specific and differentiation specific genes.

Inhibition of hemoglobin accumulation by monoclonal antibodies to the human transferrin receptor is reversed by hemin.

We have studied the effects of hemin on the inhibition of K562 cell erythroid differentiation mediated by a monoclonal antibody to the human transferrin receptor. In the absence of hemin, the monoclonal antibody 42/6 suppresses the increase of hemoglobin accumulation induced by butyric acid or 5-azacytidine (5-azaCR). In contrast, in the presence of hemin, the hemin-resistant K562(h) cell line is induced to hemoglobin production by treatment with 5-azaCR even in the presence of the monoclonal antibody to human transferrin receptor.

Treatment of leiomyomata with intranasal or subcutaneous leuprolide, a gonadotropin-releasing hormone agonist.

Fourteen premenopausal women with uterine leiomyomata were randomized to receive a gonadotropin-releasing hormone agonist (GnRH-a), leuprolide, either by daily subcutaneous (SC) injection (500 micrograms/day) or by intranasal (IN) spray (1600 micrograms/day) for 24 weeks. In the SC group, a significant reduction in uterine volume occurred from a pretreatment volume of 368 +/- 60 (mean +/- standard error of the mean [SEM]) cm3 to 202 +/- 61 cm3 at 12 weeks of therapy (P less than 0.01) and to 172 +/- 49 cm3 at 24 weeks of therapy (P less than 0.

Immunosuppressive effects of danazol in vitro.

The effects of danazol on leukocyte activation in vitro were compared with those of other known immunosuppressive steroids. Danazol at a concentration of 10(-6) M, the systemic level in women taking 600 mg/day, significantly inhibited lymphocyte proliferation in cultures activated by T-cell mitogens (Concanavalin A and phytohemagglutinin) and allogeneic mixed lymphocyte culture (MLC). Comparable immunosuppressive effects were achieved in these assay systems with dexamethasone at a concentration of 10(-8) M, and with cortisol and progesterone at a concentration of 10(-6) M.

The effects of nicotine, cotinine and anabasine on rat adrenal 11 beta-hydroxylase and 21-hydroxylase.

The effects of nicotine, cotinine and anabasine on rat adrenal steroidogenesis were examined by spectral and enzymatic techniques. The addition of nicotine, cotinine or anabasine to preparations of rat adrenal mitochondria produced type II cytochrome P-450 difference spectra. The addition of nicotine or anabasine, but not cotinine, to rat adrenal microsomes yielded type II cytochrome P-450 difference spectra.

Androgen and insulin response to an oral glucose challenge in hyperandrogenic women.

To further investigate the relationship between insulin and androgen secretion in hyperandrogenic women, the authors measured the response of serum insulin and androgen concentrations to an 8 A.M. oral glucose tolerance test (OGTT) in ten hyperandrogenic (HA) women and seven midfollicular phase control subjects.

Clustering of undermethylated CCGG and GCGC sequences in the 5' region of the Ha-ras-1 oncogene of human leukemic K562 cells.

The methylation state of the CCGG and GCGC sites of the Ha-ras-1 oncogene was analysed in the human leukemic K562 cell line, which was found to actively transcribe this gene. The results obtained demonstrate that the Ha-ras-1 oncogene is extensively methylated in both exonic, intronic, VTR and 3' untranslated portions, while undermethylations are present in a CG-rich island localized upstream of exon 1, near putative transcription initiation signals. Treatment of K562 cells with 5-azacytidine induces undermethylation of the Ha-ras-1 oncogene without major differences in the accumulation of Ha-ras-1 mRNA transcripts.

Serum steroid hormone profiles in postmenopausal smokers and nonsmokers.

Morning serum steroid levels were determined in postmenopausal chronic smokers and nonsmokers. Postmenopausal smokers (n = 9) had significantly elevated levels of cortisol, progesterone (P), 17-hydroxyprogesterone (17-OHP), androstenedione, and testosterone compared with nonsmokers (n = 16). The increases were most significant for cortisol (P less than 0.

Detection of T8 (suppressor/cytotoxic) lymphocytes in human ovarian follicular fluid.

Clear ovarian follicular fluid and the follicular flush (bloody) of aspirated follicles from 18 women undergoing oocyte retrieval for in vitro fertilization were tested for the presence of T-lymphocyte subpopulations with the use of a panel of monoclonal antibodies in indirect immunofluorescence assay. A sample of peripheral venous blood from each patient was run as a control. There was no difference in the percentage of cells positive for the various markers between bloody follicular fluid (i.

Regulation of the expression of class II genes of the human major histocompatibility complex in tumor cells.

The control of expression of human class II MHC genes has been studied in lymphoid and melanoma cells. Specific unmethylation of all restriction sites nearby the promoter regions has been detected in all cell lines and tissues studied, irrespective of their ability to express class II MHC products. The main functional role of DNA methylation appears, on the contrary, to be the regulation of a fraction of the nucleotide polymorphism of class II MHC genes.

Localization of beta-hydroxysteroid dehydrogenase in Anguilla anguilla testis.

The histochemical reaction for 3 beta-hydroxysteroid dehydrogenase was applied to glutaraldehyde fixed eel testis and successively processed for transmission electron microscopy. The reaction product was found only on the smooth endoplasmic reticulum and in the intermembrane space of mitochondria of the Leydig cells of hCG treated silver eels. The positive cytochemical reaction appears to be coupled with an enlargement of the Leydig cells and an increase of their smooth endoplasmic reticulum.