PubMed Health⌕ Search

Biomedical subjects

F Furukawa

Publications and source records attributed to F Furukawa.

At least 19 recordsLinked to original sources
PubMed1992

Molecular cloning and characterization of type VII collagen cDNA.

Type VII collagen, located in human epidermal basement membrane, is the primary pathogenic target molecule in epidermolysis bullosa acquisita and epidermolysis bullosa dystrophica. Using a monoclonal antibody against the non-collagenous domain of type VII collagen, approximately 1 Kb cDNA was isolated from human keratinocyte library. The deduced primary structure of this clone thus reflects the non-collagenous domain of type VII collagen that may be involved in cell attachment. This region shows a weak homology (approximately 23%) to the cell attachment domain of fibronectin. Northern blot revealed approximately 9.5 Kb single band.

Amino Acid Sequence↗
PubMed1992

Expression of cadherin cell adhesion molecules during human skin development: morphogenesis of epidermis, hair follicles and eccrine sweat ducts.

Expression of E (epithelia) and P (placental) cadherin cell adhesion molecules was examined immunohistochemically using human developing skin. In adult skin, E-cadherin was expressed on cell surfaces of whole epidermal layers including skin appendages, whereas P-cadherin was expressed only on those of basal layers and the outer layers of skin appendages, which was consistent with the compartment of proliferating cells. In fetal skin, while the patterns of E- and P-cadherin expression were generally similar to those in the adult, P-cadherin temporarily showed a unique spatiotemporal expression pattern in developing sweat ducts. During this stage, the expression of P-cadherin accumulated in the epidermal ridges and showed a discrepancy with the compartment of proliferating cells. These results suggest that the expression of P-cadherin is spatiotemporally controlled, and may be closely related to the segregation of basal layers as well as to the arrangement of epidermal cells into eccrine sweat ducts, but is not closely related to cell proliferation.

Adult↗
PubMed1992

Immunohistochemical localization of proliferating cell nuclear antigen/cyclin in human skin.

Expression of proliferating cell nuclear antigen/cyclin (PCNA/cyclin) in skin tissue specimens and cultured keratinocytes was studied using a monospecific antibody, obtained from a patient with systemic lupus erythematosus, and a monoclonal antibody. Indirect immunofluorescent staining revealed that cultured keratinocytes obtained from human foreskins expressed PCNA/cyclin as variable nuclear patterns in 15-30% of the cells. In normal human skin tissue specimens, PCNA/cyclin was demonstrated in only a few basal cells. Interestingly, PCNA/cyclin was expressed strongly in almost all the cells of the lowest layer of the epidermis adjacent to squamous cell carcinomas, whereas the tumor aggregates themselves had no positive staining. In contrast, no such characteristic staining was demonstrated in specimens of basal cell carcinoma. The staining pattern of PCNA/cyclin was different from that of Ki-67 in the skin tissue specimens. Our results suggest that PCNA/cyclin could be a useful marker of cell proliferation.

Antigens, Neoplasm↗
PubMed1992

Histological detection of c-myb and c-myc proto-oncogene expression in infiltrating cells in cutaneous lupus erythematosus-like lesions of MRL/l mice by in situ hybridization.

A relationship between lymphocytic activation and the overexpression of proto-oncogenes such as c-myb or c-myc has been demonstrated in human autoimmune disease. In autoimmune-prone MRL/l mice, which spontaneously develop lupus erythematosus (LE)-like lesions on the back, increased expression of myb RNA has been found in the lymphoid organs. We detected the overexpression of c-myb and c-myc proto-oncogenes in infiltrating cells in the cutaneous lesions of MRL/l mice by using in situ hybridization. No specific hybridization signals of either of the probes used were seen in the nonlesional skin of MRL/l mice or in the apparently normal skin of aged MRL/n and young MRL/l mice. These results suggest that the increased expression of myb and myc proto-oncogenes in the cutaneous LE-like lesions of MRL/l mice is related to a state of activation in the infiltrating cells and is involved in the development of these lesions.

Animals↗
PubMed1992

Lack of carcinogenicity of ferric chloride in F344 rats.

The carcinogenicity of ferric chloride, a compound that is used as a food additive, a haemostatic or treatment for hypochromic anaemia, was examined in F344 rats of both sexes. It was dissolved in distilled water at levels of 0, 0.25 or 0.5%, and groups of 50 male and 50 female rats were given one of these solutions ad lib. as their drinking water for up to 2 yr. The mean body weights of the treated rats were lower than control group values for both males and females. A variety of tumours developed in all groups, including the control group, but all these neoplasms were histologically similar to those known to occur spontaneously in this strain of rats, and no statistically significant increase in the incidence of any tumour was found in the treated groups of either sex. Thus it is concluded that under the conditions of this experiment, ferric chloride exerts no carcinogenic potential in F344 rats.

Animals↗
PubMed1992

Inhibitory effects of crude soybean trypsin inhibitor on pancreatic ductal carcinogenesis in hamsters after initiation with N-nitrosobis(2-oxopropyl)amine.

The effects of soybean trypsin inhibitor (SBTI) administration during the promotion phase of pancreatic carcinogenesis were investigated. Female Syrian golden hamsters were given three weekly s.c. injections of N-nitrosobis(2-oxopropyl)amine (BOP) each at a dose of 10 mg/kg and then administered 5% SBTI diet for the following 37 weeks. Additional groups of animals received the BOP injection alone or the 5% SBTI diet alone as controls. At week 40 of the experiment, all surviving animals were killed and development of pancreatic lesions was assessed histopathologically. The results showed that the incidence of dysplastic lesions in hamsters of the BOP/SBTI group was significantly decreased as compared to that of the BOP group (P < 0.01). A similar but not significant tendency was also found for pancreatic adenocarcinomas. In addition, the number of dysplastic lesions in the pancreas head portion in the BOP/SBTI group were significantly decreased as compared to the BOP group value (P < 0.05). Furthermore, atrophic changes of the pancreatic exocrine tissue were more severe in the BOP group than in the BOP/SBTI group (P < 0.01), indicating that SBTI treatment gave effective protection against the replacement process of acinar cell induced by BOP. Thus, the present experiment demonstrated that SBTI can inhibit hamster pancreatic ductal carcinogenesis when given in the promotion phase, in clear contrast to the enhancing effects reported for preneoplastic acinar lesion development in rats.

Animals↗
PubMed1992

Promoting effects of cigarette smoke on the respiratory tract carcinogenesis of Syrian golden hamsters treated with diethylnitrosamine.

The potential short-term promoting effects of cigarette smoke on the development of tumors in the respiratory system were investigated in male Syrian golden hamsters. Three groups (1, 2 and 3) of 30 animals each received a single s.c. injection of 100 mg/kg body wt of diethylnitrosamine (DEN) at the commencement of experiment 1. They were then exposed to non-filter cigarette (NC) smoke, filter-tip cigarette (FC) smoke and sham smoke respectively, in a Hamburg II type smoking machine from week 1 to week 12. In addition, groups 4, 5 and 6 (10 animals each) were exposed to the NC smoke, FC smoke or sham smoke respectively, for the same time period without prior DEN treatment. In the DEN-treated groups, epithelial hyperplasias and/or papillomas were induced, the incidences and numbers/animal of these lesions in groups 1 and 2 being significantly increased as compared to group 3 values. In experiment 2, two groups of 25 hamsters each were exposed to cigarette smoke or sham smoke for up to 12 weeks, five animals in each group being killed for immunohistochemical analysis using BrdU antibodies and measurement of lipid peroxides in the lung and serum at weeks 1, 2, 4, 8 and 12. Small aggregations of macrophages (smoke cells) in the lung alveoli was observed in the smoke-exposed group, but no significant increase in the numbers of BrdU positive cells in any compartment of the respiratory system was apparent. Animals of this group showed a tendency for increased lung malondialdehyde levels at weeks 2 and 12, but not weeks 4 and 8.

Animals↗
PubMed1992

Inhibitory effect of calcium chloride on gastric carcinogenesis in rats after treatment with N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride.

The effects of calcium chloride on glandular stomach carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium chloride were investigated in male outbred Wistar rats. Animals were given MNNG solution (100 p.p.m.) as drinking water and simultaneously fed a diet supplemented with 5% sodium chloride for 8 weeks. Matched negative controls received neither MNNG nor sodium chloride. Rats were then fed basal diet and given calcium chloride solution (1 or 0.2%) or tap water for the following 52 weeks. The incidences and multiplicities of preneoplastic hyperplasias in the glandular stomachs of rats given MNNG/sodium chloride followed by 1 and 0.2% calcium chloride were significantly lower than those in rats given MNNG/sodium chloride alone. The inhibitory effects of calcium were exerted in a dose-dependent manner. Calcium treatment also showed a tendency to inhibit the development of gastric adenocarcinomas although this was not statistically significant. Rats without carcinogen treatment had neither carcinomas nor preneoplastic hyperplasias in the glandular stomach. Calcium intake also significantly reduced the levels of malondialdehyde, a measure of lipid peroxidation, in the gastric mucosa and urine, the former in a dose-dependent manner. Thus, calcium chloride exerted inhibitory effects when given during the post-initiation phase of two-stage glandular stomach carcinogenesis in rats.

Animals↗
PubMed1992

Effects of caffeine, nicotine, ethanol and sodium selenite on pancreatic carcinogenesis in hamsters after initiation with N-nitrosobis(2-oxopropyl)amine.

The modulating effects of caffeine, nicotine, ethanol and sodium selenite on development of N-nitrosobis(2-oxopropyl)-amine (BOP)-initiated pancreatic tumors were investigated. Female Syrian golden hamsters were given s.c. injections of BOP (10 mg/kg body weight) or saline alone once a week for 3 weeks and then administered 2000 p.p.m. caffeine, 25 p.p.m. nicotine, 20% ethanol or 4 p.p.m. sodium selenite in their drinking water for the next 37 weeks. Control animals were given tap water alone after BOP initiation. Only the BOP-treated groups developed pancreatic adenocarcinomas and dysplasias. The multiplicity of pancreatic carcinomas was significantly higher (P less than 0.05) in animals receiving caffeine than in the controls. In addition, caffeine treatment slightly increased the incidence of carcinomas. Nicotine and ethanol also showed tendencies to enhance pancreatic carcinogenesis, although there were statistically no significant differences regarding lesion development. In contrast, sodium selenite administration was associated with a tendency for a decrease in the number of carcinomas and dysplasias. Thus, among these chemicals of obvious significance to human life-style, caffeine enhanced the development of pancreatic tumors when administered during the post-initiation phase in this hamster model.

Animals↗
PubMed1992

Induction of pancreatic tumors in male Syrian golden hamsters by intraperitoneal N-methyl-N-nitrosourea injection.

The carcinogenic effects of N-methyl-N-nitrosourea (MNU) in male Syrian golden hamsters were investigated. After single i.p. administration of MNU at doses of 50 mg/kg or 10 mg/kg, or after five fractionated i.p. injections to make a total dose of 50 mg/kg body weight (10 mg x 5), histopathological examinations were performed at the end of 40th week of the experiment. Neoplastic changes were observed in various organs, and lesions in the pancreas, forestomach, and adrenal gland were predominant. In the pancreas, three tumor types were observed: ductal adenocarcinomas, acinar cell carcinomas, and islet cell carcinomas. The incidences of pancreatic ductal carcinomas were 56, 27, and 0% in the single 50-mg, fractionated 50-mg, and single 10-mg groups, respectively. Two islet carcinomas were observed in the single 50-mg group, and an islet carcinoma and an acinar cell carcinoma were also observed in the fractionated 50-mg group. Several miscellaneous neoplastic lesions, including squamous cell papillomas/carcinomas in the forestomach, cortical adenomas in the adrenal glands, and a seminoma in the testis were also observed. These results indicate MNU to be a multipotent carcinogen with the pancreas as a target organ in the Syrian golden hamster under this experimental condition. The observed high induction rate for pancreatic ductal carcinoma suggests that this MNU protocol is a useful candidate model for experimental pancreatic ductal carcinogenesis.

Animals↗
PubMed1992

Induction of 72-kD heat shock protein and cytoskeleton damage by cytotoxic prostaglandin delta 12-PGJ2 in transformed human epidermal cells in culture.

Cyclopentenone prostaglandins (PG) such as delta 12-PGJ2 and PGA are potent inhibitors of growth in a variety of cultured cells, including human epidermal cells. To clarify the mechanism of PG cytotoxicity in human epidermal cells, we examined the effects of delta 12-PGJ2 on the induction of a heat shock protein (HSP), and on the organization of cytoskeletons in the HSC-I-transformed human epidermal cell line. Immunoblot analysis using a monoclonal antibody specific for the 72-kD heat shock protein (HSP72) revealed that a 12-h incubation with 5 micrograms/ml of delta 12-PGJ2 induced HSP72 formation in HSC-I cells. HSP72 was also induced by heat shock treatment at 43 degrees C for 90 min. The quantity of HSP72 produced was markedly decreased by co-treatment with 1 microgram/ml of cycloheximide in delta 12-PGJ2-treated cells, and similarly reduced in HSC-I cells following heat treatment. Immunofluorescence using a monoclonal antibody to HSP72 demonstrated that HSP72 was localized mainly in the cytoplasm of HSC-I cells. Following treatment with 5 micrograms/ml of delta 12-PGJ2, however, HSP72 was found in the nucleolus as well as in the cytoplasm. The accumulation of HSP in the nucleolus was similarly prominent in HSC-I cells after treatment at 43 degrees C for 90 min. Addition of delta 12-PGJ2 to confluent HSC-1 cells resulted in the disappearance of actin filaments and the disarrangement of keratin filaments, as visualized with fluorescent-labeled phallacidine or immunofluorescence. These results suggest that the cytotoxicity of cyclopentenone PG is related to the induction of HSP72, and to cytoskeleton damage in transformed human epidermal cells in culture.

Actins↗
PubMed1992

Restriction of cicatricial pemphigoid antigens to the lamina densa: confirmation by indirect immunoelectron microscopy.

Circulating anti-basement membrane zone (BMZ) antibodies in a patient with cicatricial pemphigoid (CP) were examined using an indirect immunofluorescence test, indirect immunoperoxidase electron microscopy, and Western blot analysis. An indirect immunofluorescence test on salt-split skin revealed that the anti-BMZ antibodies reacted solely to the dermal side at the separating epidermal-dermal interface, and indirect immunoelectron microscopy on intact skin indicated localization of the corresponding antigens (CP antigens) over the lamina densa and within the lower half of the lamina lucida; there were no CP antigens beneath a melanocyte. Indirect immunoelectron microscopy on salt-split skin demonstrated that the CP antigens were partly dissociated from, but restricted to, the lamina densa. Western blot analysis showed no differences in molecular weight between the CP antigens and bullous pemphigoid (BP) antigens. CP antigens, as detected by this patient's serum, appear to be constituted of molecules quite similar to BP antigens, but with different epitopes. CP antigens may be shed from basal cells and locate in the area of anchoring filaments, where they play a role in connecting basal cells to the underlying lamina densa.

Autoantibodies↗
PubMed1992

Modifying effects of soybean trypsin inhibitor on development of eosinophilic nodules and basophilic foci in the exocrine pancreas of male Sprague-Dawley rats treated with 4-hydroxyaminoquinoline 1-oxide.

Administration of 4-hydroxyaminoquinoline 1-oxide (HAQO) to rats results in development of 2 types of pancreatic acinar lesions, namely eosinophilic nodules and basophilic foci. To cast light on the biological character of these lesions, 5-week-old male Sprague-Dawley rats were given a single intravenous injection of HAQO at a dose of 7 mg/kg and, thereafter, fed soybean trypsin inhibitor (SBTI) at dose levels of 10% and 5%. At week 57, all rats were killed for pathological examination of pancreatic tissue. The incidence of eosinophilic nodules was significantly higher in the HAQO/SBTI group than in the HAQO-alone group, whereas the basophilic acinar foci were observed to occur less frequently and to be smaller in the HAQO/SBTI-treated animals. Administration of SBTI is known to increase the blood level of cholecystokinin, a trophic factor for pancreatic acinar cells. Thus, the present findings suggest that long-term elevation of this endocrine factor can affect the two types of pancreatic acinar lesions in essentially different ways, namely enhancing development of eosinophilic nodules, while suppressing the occurrence of basophilic foci.

4-Hydroxyaminoquinoline-1-oxide↗
PubMed1992

[Studies on cell proliferation activities in acute toxic lesions in the liver and pancreas of hamsters treated with N-nitrosobis(2-oxopropyl)amine].

Histopathology and cell proliferation activities in acute toxic lesions in the liver and pancreas of female Syrian hamsters given a S.C. injection of N-nitrosobis(2-oxopropyl)amine (BOP) at a dose of 100 mg/kg, were investigated. Histologically, at one day after administration, hypertrophy and focal necrosis of the hepatocytes were observed, whereas no remarkable changes were seen in the pancreas. At 7 days after administration, when diffuse hypertrophy, vacuolation and necrosis of the hepatocytes, and atypical hyperplasia of the bile duct were seen in the liver, hyperplasia of the pancreatic duct and focal necrosis and vacuolation of the acinar cells were noticed in the pancreas. Immunohistochemistry for both 5-bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) revealed remarkable increases of cell proliferation activities in the target cells for BOP toxicity, especially at 7 days after BOP treatment. Meanwhile, the number per nucleus of silver-stained proteins related to nucleolar organizer regions (AgNOR) was significantly increased in the target cells at both 1 and 7 days after BOP treatment. Thus, in the present study, it was suggested that acute toxic changes in the liver of hamsters treated with BOP precedes those in the pancreas. The speculation that AgNOR may be an indicator recognizing earlier alterations on acute BOP toxicity remains to be examined.

Animals↗
PubMed1992

[13-week subchronic toxicity study of 1,1-bis(t-butylperoxy) 3,3,5-trimethyl cyclohexane in mice].

A 13-week subchronic toxicity study of 1,1-bis(t-butylperoxy)3,3,5-trimethyl cyclohexane (TMCH) was performed in male and female B6C3F1 mice by feeding a CRF-1 powder diet containing 0, 0.5, 1.0, 2.0 and 4.0% TMCH, to determine the maximum tolerable dose (MTD) for subsequent carcinogenicity study. Mice were randomly divided into 5 groups, each consisting of 10 males and 10 females. Eight animals of both sexes in the 4.0% TMCH group died during the early administration period. Suppression of body weight gains was marked in both sexes of the 4.0% and 2.0% TMCH groups as compared with the control group. The mean food consumption in all groups treated with TMCH was lower than that in the control group in a dose-related manner. Hematological examination revealed decreases in the number of erythrocytes, volume of hemoglobin, and values for hematocrit and mean corpuscular volume (MCV) in both sexes of the 4.0% and 2.0% TMCH groups. The relative liver weights of all groups treated with TMCH increased in a dose-related manner, whereas both absolute and relative spleen weights decreased in a dose-dependent manner. Histopathologically, swelling of the hepatocytes was found centrilobularly or diffusely in both sexes of the 1.0, 2.0 and 4.0% TMCH groups, and decrease of the hematopoietic cells in the bone marrow was observed in both sexes of the 2.0 and 4.0% TMCH groups. In addition, atrophy of red pulp and white pulp of the spleen was found in both sexes of the 2% and 4% TMCH groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Stimulation of anti-RNP antibody binding to cultured keratinocytes by estradiol.

Antibodies to extractable nuclear antigens (ENA) are frequently demonstrated in the serum of patients with cutaneous lupus erythematosus. To gain a better understanding of the influence of sex hormones on cutaneous lupus, we investigated the in vitro binding of anti-ENA antibodies to cultured human keratinocytes. Estradiol-beta augmented the binding of anti-RNP, anti-SS-A/Ro, and anti-SS-B/La antibodies to cultured cells, but produced no enhancement of the binding of anti-Sm antibodies. In addition, we examined the effects of 16-alpha-hydroxyestrone, a highly estrogenic metabolite, on the binding of anti-ENA antibodies to cultured cells. This agent did not produce any augmentation of binding. Based on these experiments, we discuss the influence of estradiol on cutaneous lupus.

Antibodies, Antinuclear↗