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Biomedical subjects

F Furukawa

Publications and source records attributed to F Furukawa.

At least 253 records · Page 14Linked to original sources
PubMed1988

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. In the back skin of MRL/l mice, an age-dependent decrease of HMT activity was observed along with a corresponding decrease in histamine concentration, whereas an age-dependent increase of both HMT activity and histamine concentration was demonstrated in BXSB mice and other control mouse strains. Autoimmune-prone male BXSB mice and non-autoimmune female BXSB mice at 5 mo of age showed similar HMT activity. Corticosteroid treatment restored HMT activity in the skin of MRL/l mice but not in MRL/n mice. In addition, the change in HMT activity in MRL/l mice treated with corticosteroid appeared earlier than changes in clinicopathological examinations including skin eruptions, dermatopathology and proteinuria. Diamine oxidase (DAO) activity, another major metabolizing enzyme, was not detected in the skin of any autoimmune or control mouse strains. These findings suggest that the low activity of HMT in the skin of MRL/l mice plays a significant pathological role in the development of spontaneous lupus-like eruption. In other mouse strains, it is assumed that HMT activity is regulated by genetic factors.

Abdomen↗
PubMed1988

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 0.25% RA significantly (P less than 0.05) increased the incidence of forestomach tumors (squamous cell papilloma and carcinoma) to 60% (9/15, 2 rats with carcinoma) from 15% (3/20, one rat with carcinoma) in the group given RA-free water. In rats given 1% BHA, RA co-administered at a dose of 0.05, 0.1, 0.2 or 0.25% showed a dose-dependent enhancing effect on the development of the BHA-induced epithelial hyperplasia. Tumors, all papillomas, were induced in 3 rats (17%) with 0.25% RA and in one rat (10%) with 0.05% RA co-administration. RA alone did not induce hyperplastic changes in the forestomach. These findings indicate that RA acted as a co-carcinogen in the BHA forestomach carcinogenesis of the rat.

Animals↗
PubMed1988

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). BABL/c nude mice engrafted with thymuses from newborn C57BL/6J mice accepted the skin from either thymus donor-type mice or from host-type mice. By contrast, such thymic chimeras rejected skin grafts from a third-party donor. CTLs from nude mice engrafted with C57BL/6J thymuses were cytotoxic to target cells of the third party but not to target cells of the host-type or of the thymus-type. In the MLR assay, spleen cells of nude mice engrafted with C57BL/6J thymuses responded vigorously to third party cells and only slightly to cells of the thymus-type. Low levels of serum IgG and high titers of IgM antibodies to nuclear antigens (but not dsDNA) or skin basal cells were also found in nude mice. Antibodies to both nuclear antigens and skin basal cells disappeared after transplantation of syngeneic thymuses, but not after transplantation of allogeneic thymuses. By contrast, serum IgG levels were restored to normal in nude mice engrafted with either syngeneic or allogeneic thymuses. These results suggest that either HLA-matched or HLA-mismatched thymus grafts may become a viable treatment for certain patients with T cell deficiencies associated with deficient development or maintenance of thymic structure and/or function.

Animals↗
PubMed1987

Effects of ultraviolet light irradiation on the skin of MRL/l mice.

MRL/Mp-lpr/lpr (MRL/l) and MRL/Mp-+/+ mice were irradiated with middle-wavelength ultraviolet light (UVB), and the development of skin lesions, skin lupus band test (LBT), anti-DNA antibodies in sera, and the extent of glomerulonephritis of the kidney were examined. Long-term exposure to low doses of UVB irradiation accelerated the development of skin lesions and enhanced the intensity of the positive skin lupus band in MRL/l mice. The contents of anti-DNA antibodies in sera, the incidence of positive findings in LBT, and the extent of glomerulonephritis were not influenced by the UVB irradiation. The promotion of the development of the skin lesions in MRL/l mice by the UVB exposure was not considered to be associated with acceleration of systemic autoimmune phenomena.

Animals↗
PubMed1987

Effects of colchicine and cytochalasin B on distribution of concanavalin A receptors in isolated and cultured guinea pig epidermal cells.

Regulation of the distribution of concanavalin A (Con A)/receptor complexes by the cytoskeletal contracture system was studied in guinea pig epidermal cells in suspension and culture using the fluorescence double staining method. After treatment with 100 micrograms/ml of Con A at 37 degrees C for 30 min lectin/receptor complexes were endocytosed by the less-differentiated cells in suspension and by the adherent cells in 1- and 3-day cultures that represent a growing cell fraction. The same treatment resulted in diffuse surface distribution of the complexes in the well-differentiated cells in suspension. Colchicine (10(-5) and 10(-6) M) inhibited internalization of the complexes with resultant diffuse distribution in 60% of the adherent cells in culture. Cytochalasin B (5 and 10 micrograms/ml) not only inhibited endocytosis but promoted formation of surface patchy clumps of the complexes in suspended, less-differentiated cells and cultured adherent cells. The distribution profile was not influenced by these drug treatments in the well-differentiated cells. SDS polyacrylamide gel electrophoresis and autoradiography of 125I-labelled epidermal membranes revealed several Con A-reactive polypeptides common to the cells at various differentiation steps. The progressive decrease in endocytosis and mobility of Con A/receptor complexes was suggested to occur with differentiation. In the germinative cells the distribution of lectin/receptor complexes seemed to be regulated by microfilaments and microtubules.

Animals↗
PubMed1987

An immunohistochemical study of intracranial germ cell tumours.

Histologically verified intracranial tumours, mainly germ cell tumours of the pineal and suprasellar regions, were studied immunohistochemically using anti-serum of alpha fetoprotein (AFP), human chorionic gonadotropin (HCG), carcinoembryonic antigen (CEA), human placental lactogen (HPL), pregnancy specific beta-1 glycoprotein (SP-1), glial fibrillary acidic protein (GFAP), S-100 and neuron specific enolase (NSE). In germinomas, HCG positive cells were occasionally demonstrated in cells presenting as syncytiotrophoblastic giant cells (STGC), and GFAP and S-100 positive cells were found in the surrounding gliotic lesions. Teratomas were positive for CEA in their epithelial components. Endodermal sinus tumours were positive for AFP, choriocarcinomas for HCG and SP-1, and embryonal carcinomas for AFP, HCG and SP-1. HCG and SP-1 positive cells were demonstrated in STGC. As for the relationship between serum AFP level and tissue localization, many cases presenting a serum AFP level exceeding 220 ng/ml were positive for AFP in tumour tissue.

Adolescent↗
PubMed1987

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 0.05% and groups of 50 male and 50 female rats were administered these doses ad lib. for 2 yr. Survival of the treated male and female rats was similar to that of the corresponding controls. There was a dose-related decrease in mean body weight of treated female rats, but body weights of treated male rats were similar to those of controls. A variety of tumours developed in all groups including the control group, but all of the neoplasms that were observed were histologically similar to known spontaneous tumours in this strain of rats and no statistically significant increase in the incidence of any particular tumour type was evident in the treated groups of either sex. Nor was there any evidence of accelerated tumour induction in any phenytoin-treated group. Thus, it is concluded that under the conditions used in this experiment phenytoin had no carcinogenic potential in F344 rats.

Animals↗
PubMed1987

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. 7,12-Dimethylbenz(a)anthracene (DMBA) at a total dose of 100 micrograms was used as a positive control compound. AF-2 induced skin tumors in 35% of the mice (average of 0.4 tumors/mouse), HBA in 15% in (0.2/mouse), BHT in 13% (0.13/mouse) and quercetin in 5% (0.1/mouse). No tumors appeared in the groups treated with either test chemicals alone or TPA alone. Statistical analysis according to either Fisher's exact test or Peto's trend test revealed significant differences for tumor appearance in the AF-2/TPA and BHA/TPA followed by TPA groups as compared to in the DMSO/TPA group. The results indicate that AF-2 and BHA have weak tumor initiating activity on mouse skin, but such effects are not apparent for BHT or quercetin.

Animals↗
PubMed1987

Mammary and renal tumor induction by low doses of adriamycin in Sprague-Dawley rats.

The oncogenic potential of adriamycin was studied in both sexes of Sprague-Dawley rats. Single i.v. injection of 10 or 2 mg and repeated injections of 2 mg of adriamycin/kg body wt within 2 weeks were performed on rats, 50 days old at the commencement. All surviving animals were killed at 52 weeks of the experiment. Multiple mammary tumors, mostly fibroadenomas, were observed in 30 and 41% of the females given single low (2 mg/kg) or repeated doses (5 X 2 mg/kg) respectively. These incidences were significantly higher than those for the corresponding control group (8%). Two male rats in the low dose group also developed mammary tumors. Both sexes receiving the single high dose (10 mg/kg) injection demonstrated early mortality due to marked toxicity. The mortality of five repeated-treatment group was lower than a single high-dose group. Renal cell tumors were evident in five rats of the single, low dose groups and dysplastic foci of renal tubular epithelium occurred in the groups given a single low or repeated doses of adriamycin. Thus the present experiment provides preliminary indication of carcinogenic potential of this chemotherapeutic agent for both kidney and mammary gland of Sprague-Dawley rats and further investigations are necessary to evaluate the carcinogenic risk of adriamycin treatment.

Adenocarcinoma↗
PubMed1987

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. 7,12-Dimethylbenz[a]anthracene was used as a positive control compound at a total dose of 100 micrograms. All compounds were topically applied twice weekly for 5 weeks on the dorsal skin, and then followed by similar TPA administration for 47 weeks. Trp-P-2 induced skin tumours in 30% of the mice (0.35 tumours/mouse), and Trp-P-1, MeA alpha C and Phe-P-1 in 10-20% (0.20-0.25 tumours/mouse). The smaller amounts of Lys-P-1 and IQ applied induced tumours at an incidence of 10 and 5% respectively. No tumours appeared in the groups treated with test chemicals alone or TPA alone. Statistical analysis according to either the Fisher exact test or Peto trend test revealed significant differences for tumour appearance in the Trp-P-1, Trp-P-2, MeA alpha C and Phe-P-1 followed by TPA groups as compared with that given TPA alone. The data were used to generate ID50 (50% initiating dose) values for each of the compounds.

Animals↗
PubMed1987

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. Cultured keratinocytes in this serum-free environment formed colonies of small cuboidal, healthy cells with little keratinization or stratification and demonstrated antigenic characteristics of human basal cells.

Adolescent↗
PubMed1987

High levels of anti-mitochondrial antibodies in MRL mice. Influence of anti-DNA antibodies on anti-mitochondrial antibodies measured by an enzyme-linked immunosorbent assay.

We developed an easy enzyme-linked immunosorbent assay (ELISA) for anti-mitochondrial antibodies, and detected high levels of anti-mitochondrial antibodies in MRL/Mp-lpr/lpr (MRL1/l) mice. The influence of the presence of anti-DNA antibodies in the tested sera on this assay was also evaluated. The monoclonal anti-DNA antibodies, which were made from non-immunized MRL1/l mice, did not react with the mitochondrial antigens adhering to polystyrene plates. Absorption with DNA had little effect on the levels of mitochondrial antibodies in MRL1/l sera. Our assay for mitochondria-binding antibody was very easy and sensitive, although it could not differentiate among heterogeneous anti-mitochondrial antibodies.

Animals↗
PubMed1987

High levels of IgA-containing circulating immune complex and secretory IgA in Kawasaki disease.

Sera of patients with Kawasaki disease were studied for the levels of IgA-containing (C3-fixing) circulating immune complexes (IgA-CIC), IgG-containing (IgG-)CIC, total IgA, secretory IgA, and complement component (C3) by means of enzyme-linked immunosorbent assays or single radial immunodiffusion methods. There was significantly high level of IgA-CIC, but not IgG-CIC. The levels of total IgA, secretory IgA, and C3 were significantly elevated. Significantly high levels of secretory IgA were found in 22 (51%) of 43 patients. The proportion of secretory IgA to total IgA also increased. These abnormalities in the IgA system may play a role in Kawasaki disease.

Antigen-Antibody Complex↗
PubMed1987

Histochemical demonstration of colonic type mucin in glandular metaplasia and adenocarcinoma of the human urinary bladder.

Mucin in normal, metaplastic and neoplastic tissue specimens of the human urinary bladder was examined histochemically by the periodic acid-borohydride/potassium hydroxide/periodic acid-Schiff (PB/KOH/PAS) reaction and paradoxical concanavalin A (Con A) staining, both of which have been reported to detect mucins that are specific for the lower gastrointestinal tract. Normal mucosa, Brunn's nest, squamous metaplasia, transitional cell carcinoma, and squamous cell carcinoma produced only small amount of mucin and were negative for both PB/KOH/PAS and labile class III by Con A staining. However, several sections of mucin-producing metaplastic bladder lesions and many samples of adenocarcinoma arising from vesical mucosa and urachus contained PB/KOH/PAS-positive and/or labile class III mucin. Thus the colonic type mucin appeared in some materials of both benign and malignant mucin-producing lesions of the urinary bladder. The findings would be related to the embryogenesis of this organ.

Adenocarcinoma↗
PubMed1987

Enhancing effect of cysteamine hydrochloride on the development of gastroduodenal tumors induced by N-methyl-N'-nitro-N-nitrosoguanidine in F344 rats.

The effect of the duodenal ulceration induced by cysteamine hydrochloride on the development of gastroduodenal tumors initiated by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was studied in F344 rats of both sexes. Cysteamine (200 mg/kg body wt.) was administered by gastric intubation at various times, before, during or after a 16 week period of MNNG (100 mg/liter in drinking water) treatment. In the preliminary experiment, while the ulcers induced were confined to the proximal duodenum, the pyloric region of the stomach also showed slight erosion. Five of 25 male rats given cysteamine 2 weeks before the start of MNNG treatment developed adenocarcinoma in the duodenum as compared to 1 case in the MNNG alone group. In addition, animals of both sexes which received cysteamine during MNNG treatment yielded significantly increased incidences of adenocarcinoma in the pyloric area of the stomach. In line with earlier reports, the present findings suggest that mucosal damage and subsequent regeneration or proliferation of mucosa are important co-factors for MNNG-induced gastroduodenal carcinogenesis in rats.

Adenocarcinoma↗