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Biomedical subjects

F Furukawa

Publications and source records attributed to F Furukawa.

At least 235 records · Page 13Linked to original sources
PubMed1989

In situ freezing of the rat urinary bladder: DNA adduct formation in the bladder epithelium demonstrated by 32P-postlabeling assay.

In situ freezing of the urinary bladder has been demonstrated to exert tumor-initiating potential in two-stage urinary bladder carcinogenesis in the rat. In the present experiment, DNA modification was examined after in situ freezing of the whole urinary bladder performed by pinching with frozen forceps at -15 degrees C or -30 degrees C for 2 s. The 32P-postlabeling analysis revealed at least 2 DNA adducts in the epithelial cells of the urinary bladder collected 3 days after freezing. Single-strand breaks of DNA were also found by means of the alkaline elution assay in the bladder epithelium collected 10 min after freezing. Thus, the previously demonstrated tumor-initiating activity of in situ freezing in urinary bladder carcinogenesis was revealed to be associated with substantial DNA damage and adduct formation.

Animals↗
PubMed1989

[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 0.024M EDTA-0.075M NaCl (pH 7.5). The mucosa of the forestomach was scraped off gently with the edge of a cover glass, and the stratified squamous epithelium was collected by scraping off firmly with the edge of a cover glass. Since the collected epithelium cells adhere to the pipettes, these cells were transferred onto a polycarbonate filter by using a micro spatula. The dose-dependent DNA damages (5 approximately 150 mg/kg) were observed after administration of 1-methyl-3-nitro-1-nitrosoguanidine (MNNG), a forestomach carcinogen.

Animals↗
PubMed1989

[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. Immunohistochemical analysis revealed no differences in the distribution of BrdU-positive cells between treated and control rats throughout the experiment. Thus it was concluded that 1,3-DNB exerted no effects on DNA synthesis in spermatogonia and preleptotene spermatocytes. Using the lanthanum-tracer method, it was shown that although lanthanum could penetrate the intercellular space from the basement membrane, the tight junction, consisting of fusions of contiguous Sertoli cell membranes, prevented further diffusion in both control rats and those killed at 8 hr after dosing. On the other hand, at 24 hr after dosing, lanthanum penetrated into the adluminal compartment beyond the tight junctions, thus demonstrating loss of integrity of the blood-testis barrier. The results suggested that the Sertoli cell is the primary target of 1,3-DNB testicular toxicity.

Administration, Oral↗
PubMed1989

[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. An additional group received the EQ treatment alone. Calcification and stones were observed from the renal papilla to the pelvis region in all EQ treated groups. The incidence and grade of the lesion in the combined treated groups were much more greater than in the group treated with exposed to EQ alone. Ultrastructurally, microvilli on the surface of the renal papilla cells appeared degenerated or disappeared completely in the treated groups. Chemical element analysis of the renal stones revealed P and Ca to be the primary constituents. They were therefore considered to be of hydroxyapatite type.

Animals↗
PubMed1989

[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. The experiment was terminated at 41 weeks after the beginning of PNUR administration, and development of tumors in the upper digestive tract was determined histopathologically. Squamous cell tumors were observed in the oral cavity, tongue and forestomach of all PNUR treated groups, while no tumors developed in the control group. Significantly higher incidences of forestomach papillomas were observed in the groups administered VA-deficient or VA-supplemented diets, as compared with that receiving standard diet (p less than 0.01, p less than 0.05, respectively). These results thus suggest that the higher incidences of forestomach tumors were probably due to general dietary differences (semipurified vs. standard diets) and not to the VA deficiency per se.

Animals↗
PubMed1988

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. Estradiol (10(-5) to 10(-7) M) augmented binding of antiserum probes on the surface of cultured keratinocytes, with 10(-7) M estradiol showing the highest induction of cell surface binding of antisera specific for SS-A/Ro plus SS-B/La Ag (24.5% of cells were positive). In contrast, dihydrotestosterone, testosterone, and progesterone showed no augmentation. The augmentation by estradiol was partially inhibited by the antiestrogen nafoxidine. Estradiol augmented the relative incidence and absolute number of small or cuboidal cells binding antibodies specific for SS-A/Ro and SS-B/La Ag, whereas the number and incidence of larger differentiated cells binding anti-SS-A/Ro and anti-SS-B/La decreased significantly in cell cultures stimulated with estradiol. Flow cytometric analysis utilizing monospecific anti-SS-A/Ro or anti-SS-B/La sera showed that estradiol induced binding of anti-SS-A/Ro in 13.1% of cultured keratinocytes, of anti-SS-A/La in 14.4%, and of sera specific for both Ag in 21.4%. This direct association between estradiol and the augmentation of binding to the cell surface of human keratinocytes of IgG from antisera specific for SS-A/Ro and SS-B/La Ag may be a trigger factor of immunologic damage in lupus and may be important in the different sex rates observed in skin manifestation of subacute cutaneous and neonatal lupus erythematosis.

Adjuvants, Immunologic↗
PubMed1988

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. The T-cell population of female MRL/Mp-lpr/lpr mice increased markedly with age, and the B-cell population of the male BXSB mouse tended to increase. However, little change was observed with age in the NZBWF1/J mice. The immunohistochemical properties of the Peyer's patches in the three autoimmune model mice were different.

Animals↗
PubMed1988

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. The BS ratios of IgA and IgM, which are selectively secreted into bile, did not show a significant correlation with total serum bilirubin. The index of the BS ratio to the BS ratio of albumin (BS/BS-Alb index) of IgA and IgM was significantly larger than that of IgG. This indicates that the selective transport of IgA and IgM into bile is present even in patients with obstructive jaundice. Since the BS/BS-Alb index of C3 is larger than that of IgG, and the SGOT correlated directly with the BS ratio of C3, some of the C3 in bile may come from damaged hepatocytes.

Albumins↗
PubMed1988

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 0.05% for 104 weeks. Similar numbers of male and female rats received the basal diet throughout the experiment. All surviving rats were sacrificed at week 112. The rats given the chemical at 0.1% showed reduced body weight gain, especially in females, and liver dysfunction in biochemical examination of blood in males. Histopathologically, however, no significant lesions or tumor induction attributable to the treatment were observed in any tissue except for dose-dependent reduction of spontaneous leukemia in both sexes and slightly reduced incidences of pituitary and thyroid adenomas in females. Under the present experimental conditions, thiram was not carcinogenic in F344 rats.

Animals↗
PubMed1988

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. These initiating treatments were followed by administration of 0.1% phenobarbital in the drinking water for 12 weeks as the promoting regimen. Quantitative examination of placental glutathione S-transferase-positive foci revealed no enhancing effect of APAP on the induction of the foci consisting of more than two positive cells with either initiating treatment. If solitary positive hepatocytes were included in the effective number of foci, 10 repeated doses of 1 g/kg APAP increased the number of foci while the validity of the single positive cells is uncertain. This dose of APAP caused centrilobular necrosis. By 32P-postlabeling, although the active metabolite of APAP formed DNA adducts when incubated with isolated DNA, no DNA adduct formation was detected in the liver of rats either fed 0.1-1.5% APAP for 1 week or given 1 g/kg by gastric intubation. These results indicate that APAP possesses no tumor-initiating activity in the rat liver.

Acetaminophen↗
PubMed1988

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. We found that keratinocytes infected with HSV in the presence of acyclovir (ACV) expressed such antigens yet remained viable for a period of time after the onset of antigen expression such that cytotoxicity studies could be successfully performed. Rabbit skin cells, a transformed keratinocyte line, or second passage human neonatal foreskin keratinocytes were grown in culture medium with or without 200 microM ACV and were infected with HSV. Examination by direct immunofluorescence with anti-HSV antibody revealed uniform HSV antigen expression by cells both with and without ACV by 8 h after infection. Cells infected without ACV exhibited marked structural abnormalities including formation of multinucleated giant cells, while cells with ACV showed fewer such changes throughout a 24-h period. An Ethidium Bromide-Acridine Orange cytotoxicity assay demonstrated significant increases in the cytotoxicity of infected cells not protected by ACV compared to that of cells with ACV (p less than .001). This in vitro model should prove useful in the investigation of HSV specific immune mediated cytotoxicity.

Acridine Orange↗
PubMed1988

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 1.0-3.0 mM Sr2+ showed higher viability and almost a twofold increase in cell number compared with those grown in a standard calcium concentration. Time course studies revealed that 2.0 mM Sr2+ had no effects on growth of cultured melanocytes or fibroblasts. Sr2+ increased the percentage of cultured keratinocytes in G2/M phase, with a decrease in cells in G0/G1 phase. This effect of Sr2+ on the cell cycle was not seen in cultured melanocytes or fibroblasts. A 2 mM concentration of Sr2+ produced an increase in low-density keratinocytes separated by a Percoll gradient. In addition, increased expression of human fibronectin was observed in the cytoplasm and on cell membranes of keratinocytes cultured in Sr2+. Sr2+ can be of practical benefit in the culture of human keratinocytes in serum-free medium, increasing the viability and proliferative rate and producing a more uniform population of basaloid cells with increased expression of cell surface fibronectin.

Cell Count↗