[Effect of vitamin A deficiency on PNUR-induced carcinogenesis in the rat upper digestive tract].

The effects of vitamin A (VA) deficiency on 1-propyl-1-nitrosourethan (PNUR)-induced tumorigenesis in the upper digestive tract were investigated in male F344 rats. Starting at 6 weeks old, animals were given PNUR in the drinking water (200 ppm) for one week, and starting 2 weeks later, were divided into 3 groups (30 rats/group) and maintained on VA-deficient diet, VA-supplemented diet (semipurified diet) or standard diet (CRF-1), respectively. An additional control group (10 rats) was fed VA-deficient diet without PNUR treatment.

[Analysis of renal calcification and stone formation in rats treated with ethoxyquin using X-ray analytical scanning electron microscopy: ultrastructural observations and element analysis].

Rat renal calcification and stone formation were investigated using a JEOL-JSM840A scanning electron microscope (SEM) equipped with a LINK-QX200J energy dispersed X-ray detector (EDX). Male Wistar rats were treated with 100 ppm N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking water or 10% NaCl in the diet for 8 weeks, and subsequently administered a dietary supplement of 0.1% ethoxyquin (EQ) for 32 weeks.

[Application of BrdU-immunohistochemistry and lanthanum-tracer methods to the pathological evaluation of 1,3-dinitrobenzene testicular toxicity].

The pathogenesis of 1,3-dinitrobenzene (1,3-DNB)-associated testicular toxicity was investigated in Sprague-Dawley rats with 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and lanthanum-tracer methods as well as routine histopathological examination. Animals were killed at 8, 12, 24, 48 and 96 hr after a single oral administration of 1,3-DNB at a dose of 25 mg/kg. Histopathologically, severe alterations in the testes such as degenerating pachytene spermatocytes and giant cell formation were observed by 24 hr.

[Measurement of DNA damage in forestomach squamous epithelium by alkaline elution assay].

The alkaline elution assay were applied for assessing DNA damage of forestomach squamous epithelium in the male F344 rat. The animals were starved for 18 hr and then given a single oral dose of the sample in saline or corn oil. After 3 hr the stomach was removed, opened along the greater curvature and washed with cold 0.

Evaluation of ATPase-positive Langerhans' cells in skin lesions of lupus erythematosus and experimentally induced inflammations.

We examined the time-dependent dynamics of epidermal Langerhans' cells (LC) in human systemic lupus erythematosus (SLE), in MRL/Mp-lpr/lpr(MRL/lpr) mice, and in various experimental cutaneous inflammations, such as the Arthus reaction, dinitrochlorobenzene allergic dermatitis, and croton oil primary irritant dermatitis, in order to clarify the pathomechanisms of lupus skin lesions. The numbers of LC in untreated SLE patients with newly developed skin lesions decreased in the central lesional sites and increased significantly in the peripheral lesional sites. In MRL/lpr mice, the number of LC increased significantly in the central lesional sites during the initial stage and increased in the peripheral lesional sites and decreased in the central lesional sites 2-4 weeks after the onset of skin lesions.

Carcinogenicity study of tetramethylthiuram disulfide (thiram) in F344 rats.

The carcinogenic potential of tetramethylthiuram disulfide (thiram) was examined in F344 rats. Groups of 50 male and 50 female rats were given thiram in their diet at concentrations of 0.1% and 0.

Estradiol enhances binding to cultured human keratinocytes of antibodies specific for SS-A/Ro and SS-B/La. Another possible mechanism for estradiol influence of lupus erythematosus.

A strong association between anti-SS-A/Ro and anti-SS-B/La antibodies and skin lesions has been well documented in subacute cutaneous lupus erythematosus and neonatal lupus erythematosis in which 70 to 80% of patients are female. In order to better understand the mechanisms of the influence of sex hormones on cutaneous lupus, we designed immunopathological in vitro experiments to evaluate the effects of estradiol and other sex steroids on the binding of SS-A/Ro- and SS-B/La-specific antibodies to cultured human keratinocytes from neonates. Cultured human keratinocytes incubated with antisera specific for SS-A/Ro or SS-B/La Ag were fixed with either acetone or paraformaldehyde and then analyzed in indirect immunofluorescent assays or by FACS analysis to detect cell surface IgG binding as an indirect measure of SS-A/Ro and SS-B/La Ag expression on the cell surface of keratinocytes.

Study for tumor-initiating effect of acetaminophen in two-stage liver carcinogenesis of male F344 rats.

The potential liver-tumor-initiating activity of acetaminophen (paracetamol, APAP) was investigated in male F344 rats. APAP was administered by intragastric intubation either as 10 doses of 1 g/kg body weight over 5 weeks or as a single dose of 0.5 g/kg body weight 24 h after two-thirds partial hepatectomy.

Comparative studies on immunoglobulins, complement component (C3), albumin, and immunoglobulin A-containing circulating immune complexes in serum and bile of patients with biliary obstruction.

We measured the concentrations of IgA, IgG, IgM, secretory IgA, albumin, complement component (C3), and IgA-containing circulating immune complex (IgA-CIC) in the serum and bile of patients with biliary obstruction. The bile-to-serum (BS) ratio of the concentrations of albumin and IgG increased with the increase in total serum bilirubin. This indicates that the permeability from blood to bile increases with the degree of biliary obstruction, and the blood-bile barrier function breaks down.

Characterization and practical benefits of keratinocytes cultured in strontium-containing serum-free medium.

Strontium (Sr2+) can substitute for Ca2+ and stimulate a variety of functions of numerous types of cells. The purpose of this study was to investigate the details of the biologic effects of Sr2+ on human keratinocyte growth, cell cycle, viability, and differentiation and to compare these effects with Sr2+ effects on cultured skin melanocytes. Cultured keratinocytes stimulated with 1.

Development of an in vitro keratinocyte model for use in the study of HSV specific cytotoxicity.

Herpes simplex virus (HSV) specific immune mediated cytotoxicity may be involved in control of HSV infections and in the tissue damage induced by HSV infection or HSV related skin disease such as herpes associated erythema multiforme. Developing an in vitro model to study this process has proved difficult due to the lack of an appropriate target cell that will express HSV antigens but is not simultaneously subject to viral induced cell death. The purpose of this study was to develop a model in which keratinocytes express cell surface HSV specific antigens but at the same time are protected from death due to viral infection.

Co-carcinogenic effect of retinyl acetate on forestomach carcinogenesis of male F344 rats induced with butylated hydroxyanisole.

The potential modifying effect of retinyl acetate (RA) on butylated hydroxyanisole (BHA)-induced rat forestomach tumorigenesis was examined. Male F344 rats, 5 weeks of age, were maintained on diet containing 1% or 2% BHA by weight and simultaneously on drinking water supplemented with RA at various concentrations (w/v) for 52 weeks. In groups given 2% BHA, although marked hyperplastic changes of the forestomach epithelium were observed in all animals, co-administration of 0.

Pathogenesis of lupus dermatoses in autoimmune mice. X. Evaluation of histamine-N-methyltransferase activity in the skin of autoimmune.

We measured histamine concentration and its metabolizing enzymes in the skin of MRL/Mp-lpr/lpr (MRL/l) and BXSB mice to clarify the contribution of histamine metabolism to the mechanisms of the development of lupus dermatoses. The concentration of histamine seemed to differ with the mouse strain. The activity of histamine-N-methyltransferase (HMT), one of two major metabolizing enzymes, was significantly lower in the tail and back skin of MRL/l mice at the age of 5 months than in the control MRL/Mp-+/+(MRL/n) mice, although there were no characteristic differences among several mouse strains of 1 mo of age.

Immunohistochemical examination of Peyer's patches in autoimmune mice.

The distribution of T-cells and B-cells in Peyer's patches was examined in three autoimmune model mice, MRL/Mp-lpr/lpr, BXSB, NZBWF1/J mice and normal BALB/c mice, between one and ten months old. A multiple layering technique was used for immunohistochemical detection of lymphocyte surface antigens of T-cells (Thy1.2, Lyt1, Lyt2) and B-cells (surface IgM) and peanut agglutinin receptor for germinal center cells.

Immunological status of nude mice engrafted with allogeneic or syngeneic thymuses.

Restoration of T-cell functions and changes in autoantibody production were studied in BALB/c nu/nu (nude) mice engrafted with syngeneic (BALB/c) or allogeneic (C57BL/6J) thymuses across major histocompatability barriers. T-cell functions, including mitogen responses and antibody production to sheep red blood cells (SRBC), were restored in nude mice engrafted with either allogeneic or syngeneic thymuses. Alloreactivity was evaluated by analysis of the pattern of skin allograft rejection, generation of alloreactive cytotoxic T-lymphocytes (CTLs), or quantitation of mixed-lymphocyte reaction (MLR).

Initiating potential of 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and 3,3',4',5,7-pentahydroxyflavone (quercetin) in two-stage mouse skin carcinogenesis.

Tumor initiating activity of 3,3',4',5,7-pentahydroxyflavone (quercetin), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and 2-(2-furyl)-3-(5-nitro-2-furyl) (AF-2) acrylamide) were tested in a two-stage mouse skin carcinogenesis model using 12-O-tetradecanoyl phorbol-13-acetate (TPA) as a promoter. These compounds dissolved in dimethyl sulfoxide were topically applied twice weekly for 5 weeks on the dorsal skin, and then followed by TPA for 47 weeks. The total initiating dose was 100 mg for each compound.

Serum-free serial culture of adult human keratinocytes from suction-blister roof epidermis.

Coating cell culture flasks with natural extracellular matrix (ECM) enhanced the culture of adult human keratinocytes from suction-blister roof epidermis in an environment without fetal calf serum (FCS), bovine pituitary extracts or cellular feeder layers. A higher incidence of cell attachment on natural ECM was observed than on collagen and human fibronectins (HFN)-coated plastic dishes, and natural ECM was necessary for growth and proliferation of attached cells under the culture conditions used. Cells in primary culture grew to confluency on natural ECM-coated surfaces within about 14 days, and subsequent serial passage could be made up to fourth passage in collagen- and HFN-coated plastic flasks.

Long-term in vivo carcinogenicity study of phenytoin (5,5-diphenylhydantoin) in F344 rats.

The carcinogenicity of phenytoin was studied in F344/DuCrj rats. Phenytoin was mixed with powdered basal diet at levels of 0 (control), 0.025 or 0.

Initiating activity in a two-stage mouse skin model of nine mutagenic pyrolysates of amino acids, soybean globulin and proteinaceous food.

Trp-P-1, Trp-P-2, MeA alpha C, A alpha C, Glu-P-1, Glu-P-2, Lys-P-1, IQ and Phe-P-1 were tested for tumour initiating activity in a two-stage skin carcinogenesis model using 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter. The total initiating doses were 20 mg for Trp-P-1, Trp-P-2, Glu-P-1 and Glu-P-2, 40 mg for MeA alpha C and A alpha C, 5 mg for Lys-P-1, 7.5 mg for IQ and 100 mg for Phe-P-1.