Biomedical subjects

F Furukawa

Publications and source records attributed to F Furukawa.

At least 163 records · Page 9Linked to original sources

PubMed1994

Susceptibility to UVB light in cultured keratinocytes of cutaneous lupus erythematosus.

In this study, we investigated UVB-light-induced cytotoxicity and the binding of antibodies to extractable nuclear antigens on cultured keratinocytes from patients with cutaneous lupus erythematosus (LE). Keratinocytes from cutaneous LE patients showed a higher susceptibility to single-dose UVB light irradiation compared to keratinocytes from normal controls. The binding of antibodies to U1RNP and Ro/SS-A antigens on cultured keratinocytes was induced by UVB light and more up-regulated when cultured keratinocytes were reacted with autologous sera. Antibody-dependent cellular cytotoxicity (ADCC) was induced when cultured keratinocytes irradiated with UVB light were combined with autologous sera, using peripheral mononuclear cells of normal controls. Immunohistochemical studies of skin biopsy specimens from patients with systemic LE revealed an increased number of epidermal Langerhans cells at the peripheral sites of skin lesions and a relative dominance of infiltrative CD8-positive lymphocytes in the central area of skin lesions. Based on these findings we suggested that ADCC mechanisms were involved in the development of skin lesions, and the distribution of Langerhans cells and infiltrated CD8 cells were responsible for the expansion and persistence of lesions.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1994

Production of monoclonal antibodies against the N-terminal noncollagenous domain of type VII collagen encoded by epidermolysis bullosa acquisita antigen cDNA.

Eleven monoclonal antibodies were produced against the human N-terminal noncollagenous domain of type VII collagen. All antibodies were specifically bound to the epidermal basement membrane zone and did not cross-react with other dermal collagens. A binding of these antibodies was investigated with various species and revealed that the reactivities of each monoclonal antibody against rat, mouse, human and guinea pig skin differ from each other. These data may suggest that type VII collagen is antigenic to immunized small animals, i.e. the rat and mouse, and that there are multiple antigenic determinants on type VII collagen.

Animals↗

PubMed1994

A case of bullous systemic lupus erythematosus.

We report a case of bullous systemic lupus erythematosus (SLE). The patient suddenly presented with a widespread blistering eruption on the trunk and neck during the course of treatment of SLE. A skin biopsy specimen showed subepidermal blisters, and direct immunofluorescence (IF) revealed deposition of IgA, IgG and IgM at the dermoepidermal junction. Indirect IF showed linear IgG deposition along the base of 1 M NaCl-split skin. Rapid resolution of the blisters occurred following treatment with dapsone 50 mg daily.

Child↗

PubMed1994

Pemphigus associated with metastatic carcinoid.

Patients with pemphigus are occasionally associated with neoplasms. We report a case of pemphigus with carcinoid. To our knowledge, this is the first case of coexistence of pemphigus and carcinoid.

Adult↗

PubMed1994

Ultrastructural localization of E-cadherin cell adhesion molecule on the cytoplasmic membrane of keratinocytes in vivo and in vitro.

We examined the ultrastructural localization of E (epithelial)-cadherin cell adhesion molecules by immunoperoxidase electron microscopy on the epithelium of mouse intestine, epidermis of human skin, and cultured human keratinocytes. The in vivo studies demonstrated that E-cadherin was present at the intermediate junction but not at the desmosome of the mouse intestinal single epithelium, and was found on the cytoplasmic membranes of keratinocytes with condensation in the intercellular space of the desmosomes, except for the basal surface of the basal cells. In vitro studies demonstrated that keratinocytes cultured in medium containing a low Ca2+ concentration (0.1 mM) lacked the tight connection through desmosomes, and that E-cadherin showed diffuse distribution and dot-like accumulation around the free surface of the cytoplasmic membrane. In culture medium containing a high concentration of Ca2+ (0.6 mM), keratinocytes formed desmosomal adhesion structures in which E-cadherin was accumulated. The free surface of the keratinocytes in this medium showed weaker distribution and a lesser amount of dot-like accumulation of E-cadherin than that in a low Ca2+ condition. These findings suggest that the distribution pattern of the E-cadherin cell adhesion molecules on the keratinocytes is different from that on the single epithelium of the intestine, and that E-cadherin on the cytoplasmic membrane of the keratinocytes shifts to the desmosomes under physiological conditions, participating in adhesion in association with other desmosomal cadherins.

Cadherins↗

PubMed1994

[13-week subchronic toxicity study of L-histidine monohydrochloride in F344 rats].

A 13-week subchronic toxicity study of L-histidine monohydrochloride was performed in male and female F344 rats at dose levels of 0, 0.31, 0.62, 1.25, 2.5 and 5.0% in the diet, to determine the maximum tolerable dose (MTD) for subsequent investigation of carcinogenicity. Rats were randomly allocated to 6 groups, each consisting of 10 males and 10 females. No animals died during the administration period. Suppression of body weight gain and decrease in food consumption were observed in males of the 5.0% group along with hematological examination as revealed by increases in hemoglobin volume and hematocrit. Serum biochemical examination demonstrated increased levels of BUN and creatinine in females of the 5.0% group, and increased level of BUN in females of the 1.25% group. Histopathologically, sperm granulomas in the epididymis were found in half of the 5.0% group males. Based on the results of the present study, it was concluded that the MTD of L-histidine monohydrochloride is 2.5% in diet, because the dietary dose level of 5.0% proved to exert significant toxicity reflected in suppression of body weight gain and formation of sperm granulomas.

Animals↗

PubMed1994

[A 13-week subchronic toxicity study of bisphenol A in B6C3F1 mice].

A 13-week subchronic toxicity study of bisphenol A (BPA) was performed in male and female B6C3F1 mice at dose levels of 0, 0.2, 0.5, 1.0, 2.0 and 4.0% in the diet, to facilitate dose selection for a subsequent carcinogenicity study. Mice were randomly allocated to 6 groups, each consisting of 10 males and 10 females. Two 0.2% group males and two 4.0% group females died during the experimental period. Suppression of body weight gain and increase in food consumption were observed in males and females of the 4.0% groups. Hematological examination revealed decrease in number of erythrocytes, volume of hemoglobin and value of hematocrit in males and females of the groups receiving 1.0% or above, and an increase in number of platelets in males of 4.0% group. Decrease in number of erythrocytes and hematocrit value was also noticed in females of 0.5% group. Histopathologically, cystic dilatation, degeneration or regeneration of renal tublues were found in males and females of 1.0% or higher groups, multinucleated hepatocytes were increased in mice of both sexes treated with any dose of BPA, and fibrous osteodystrophy was observed in males and females of the 4.0% groups. Based on the results of the present study, it was concluded that the maximum tolerance dose (MTD) of BPA is 0.2% in diet, because the dose level of 0.5% proved to exert significant hematological toxicity.

Administration, Oral↗

PubMed1993

Pathogenesis of lupus dermatoses in autoimmune mice. XIX. Attempts to induce subepidermal immunoglobulin deposition in MRL/Mp- +/+ mice.

The deposition of immunoglobulin (Ig) at the dermo-epidermal junction (DEJ) of the skin, frequently observed in autoimmune mouse strains, is similar to that seen in patients with systemic lupus erythematosus (SLE). MRL/Mp-lpr/lpr (MRL/lpr) mice have an autosomal recessive mutant gene, lpr, which produces massive T-cell proliferation and accelerates the onset of autoimmune diseases. MRL/Mp- +/+ (MRL/n) mice lack the lpr gene, and do not develop autoimmune disease during the first year after birth under pathogen-free conditions. To verify the mechanisms of subepidermal Ig deposition in the skin of LE, we designed an experiment in which we could induce Ig deposition in the control MRL/n mice. Intraperitoneal injection of lymphoproliferative cells of aged MRL/lpr mice induced splenomegaly and splenic granulomatous angitis in the control MRL/n mice. Lipopolysaccharide (LPS), a polyclonal B-cell activator, induced slight splenomegaly and relatively high levels of serum Ig. Dermatopathological investigation revealed mild lymphocyte infiltration without positive Ig deposition at the DEJ of MRL/n mice treated with proliferative T cells. Injection of both proliferative T cells and LPS induced 50% positivity of subepidermal Ig deposition, and high levels of serum immunoglobulins and anti-double stranded DNA (anti-dsDNA) antibodies. These changes were not observed in MRL/n mice injected with thymocytes of newborn MRL/lpr mice. Skin lesions and lupus nephritis were not demonstrated in any of the mice tested. This study suggest that both the mild inflammatory reaction and the presence of anti-dsDNA antibodies are required for the induction Ig deposition at the DEJ in the skin of LE patients.

Animals↗

PubMed1993

Immunohistochemical localization of lipocortins in normal and psoriatic human skin.

The distribution of lipocortin I, a steroid-induced inhibitory protein of phospholipase A2, was examined in normal and psoriatic human skin. Using immunoblotting analysis with specific antibody against human lipocortin I purified from human placenta, lipocortin I was detected as a 37 kDa protein in cultured epidermal cells, whole skin and epidermis. In the dermis and stratum corneum, lipocortin I was only weakly detectable by Western blotting. In contrast to normal skin, much less lipocortin I was detected by Western blotting analysis in psoriatic skin. Using immunoperoxidase immunohistochemical analysis, lipocortin I was demonstrated in the cytoplasm of keratinocytes in the upper and middle layers of the epidermis and in some infiltrating cells in the dermis in normal skin. In involved psoriatic skin, by contrast, lipocortin I was almost undetectable in the epidermis, although it was demonstrated in some infiltrating cells in the dermis. No immunostaining of lipocortin I was observed in the stratum corneum of normal or psoriatic skin. These results, together with the finding that phospholipase A2 activity is higher in psoriatic epidermis than in normal epidermis, suggest that lipocortin I plays an important role in the regulation of differentiation and proliferation of epidermal keratinocytes.

Annexin A1↗

PubMed1993

Development of descending fibers to the rat embryonic spinal cord.

Onset and development of descending pathways to the rat embryonic spinal cord was examined by the use of retrograde transport of horseradish peroxidase (HRP). HRP was injected in the lower thoracic segments of the spinal cord of embryos ranging in age from embryonic day (E)14.5 to E20.5. A small number of labelled cells were found in the brain stem nuclei on E14.5: they were located in medullary as well as pontine reticular formation, lateral vestibular nucleus and interstitial nucleus of the medial longitudinal fasciculus. By E15.5 labelled cells were observed in the reticular formation of the caudal part of the medulla oblongata, medullary raphe nuclei, locus coeruleus, subcoeruleus nucleus, Barrington's nucleus and central gray of the midbrain. Cells in the red nucleus and in the nucleus of the solitary tract were labelled by E 16.5 and E17.5, respectively. Thereafter, labelled cells were first found in a few other nuclei: the gracile nucleus on E19.5 and the paraventricular nucleus on E20.5. The present study demonstrated that all the major supraspinal inputs except corticospinal fibers project to the lower thoracic spinal cord by E20.5.

Animals↗

PubMed1993

A case of cutaneous T-cell lymphoma expressing gamma delta T-cell receptors.

Cutaneous T-cell lymphoma expressing gamma delta T-cell receptors (TCRs) is rare; only a few cases have been reported. We report another case of the disease that had a fatal outcome and differs from two previously reported cases in its clinical, histologic, and immunohistochemical aspects. The patient had multiple skin tumors with central crusts; she showed no response to chemotherapy and died within 1 year. Histologic findings included perivascular infiltrates in the dermis and subcutaneous tissue with no epidermotropism; the large lymphoid cells had a phenotype of CD1-, CD3+, CD4-, CD8-, CD25-/+, CD30-, CD38-/+, HLA-DR+, and gamma delta TCR (beta F1-, TCR delta 1+, delta TCS1-, Ti gamma A+, BB3-). The differences in the phenotype of gamma delta T-cell malignancies may reflect the uniqueness of its clinical and histologic features. A study of gamma delta T-cell malignancies may disclose important biologic features of gamma delta TCR+ cells.

Antigens, CD↗

PubMed1993

Carcinogenicity study of 1,1-bis(tert-butylperoxy)-3,3,5-trimethylcyclohexane in B6C3F1 mice.

1,1-Bis(tert-butylperoxy)-3.3.5-trimethylcyclohexane (BBTC) is widely used in the manufacture of rubber. The present carcinogenicity study in B6C3F1 mice was carried out in order to assess its potential to induce tumours. BBTC was administered at dietary levels of 0 (control), 0.25 and 0.5% for 78 wk; these dose levels were selected on the basis of a subchronic toxicity study, in which body weights were depressed to less than 90% of the control group values and swelling of hepatocytes was histologically evident in animals fed 1% BBTC or more in the diet. Neoplasms were found in all groups, including the control group, but there were no significant differences between groups of either sex in mortality, tumour incidences or tumour distribution. All tumours were considered to be spontaneous because of the similarity to background data for B6C3F1 mice. This study thus provides no evidence of carcinogenicity of BBTC in B6C3F1 mice.

Anemia↗

PubMed1993

Effects of hickory smoke condensate on gastric carcinogenesis in Wistar rats after treatment with N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride.

Short-term assays in vivo have suggested that hickory smoke condensate (HSC), a food flavouring, might have tumour-initiating and/or promoting activities in the glandular stomach of the rat. In the present study, the modifying effects of HSC on glandular stomach carcinogenesis after initiation with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium chloride (MNNG salt) were investigated in male Wistar rats. Animals were given MNNG solution (100 ppm) as drinking water and simultaneously fed the diet supplemented with 5% sodium chloride for 8 wk. Matched negative controls received neither MNNG nor sodium chloride. Rats were then fed a basal diet and given HSC solution (1 or 3%) or tap water for the following 32 wk. During the experimental period, treatment with MNNG salt and administration of HSC both brought about growth retardation although the final body weight of rats was comparable between groups. Only two rats treated with MNNG salt followed by 1% HSC developed adenocarcinoma of the stomach. HSC treatment appeared to increase the number of rats with preneoplastic hyperplasias and/or adenocarcinomas in both the fundic and pyloric mucosa, although not to a statistically significant extent. HSC administration significantly increased malondialdehyde levels in the urine and gastric mucosa, the former in a dose-dependent manner. The results suggest that HSC has little, if any, promoting effect on two-stage glandular stomach carcinogenesis in rats when given during the post-initiation phase. However, the tumour co-initiating effects of HSC require further clarification.

Adenocarcinoma↗

PubMed1993

Enhancing effect of ethanol on esophageal tumor development in rats by initiation of diethylnitrosamine.

The effects of ethanol on initiation of esophageal tumorigenesis by diethylnitrosamine (DEN) were investigated in male F344 rats. Animals were administered 50 p.p.m. DEN plus 10% ethanol (Group 1), 33 p.p.m. DEN (Group 2), 50 p.p.m. DEN (Group 3) or 10% ethanol (Group 4) in the drinking water for the first 8 weeks, and were then maintained on basal diet and tap water for up to 104 weeks. The concentration of 33 p.p.m. DEN in Group 2 was an adjustment to the anticipated intake in Group 1. Consequent total intakes of DEN in Groups 2 and 3 were respectively 80% and 134% of that in Group 1. Histopathological examination of esophagus tissue after final sacrifice revealed incidences of papillomas and/or carcinomas in Groups 1, 2 and 3 to be 57.7, 3.8 and 10.7% respectively. No esophageal tumors occurred in Group 4. The incidence of hyperplasia was 100% in Group 1 in contrast to 46.2% in Group 2, 57.1% in Group 3 and 3.6% in Group 4. Thus, the incidences of esophageal proliferative lesions were significantly higher in Group 1 than in Groups 2 or 3. Our results clearly indicate that ethanol has an enhancing effect on the development of esophageal tumors induced by DEN in rats, when administered during the initiation phase.

Animals↗

PubMed1993

Temporal dissociation between cell proliferation and eosinophilic foci development in the exocrine pancreas of rats initiated with 4-hydroxyaminoquinoline 1-oxide and administered soybean trypsin inhibitor.

Male Sprague-Dawley rats received a single i.v. injection of 4-hydroxyaminoquinoline 1-oxide (HAQO) 7 mg/kg body weight or vehicle alone, and starting 7 days thereafter, were then fed basal diet with or without a 5% soybean trypsin inhibitor (SBTI) supplement. Subgroups were sequentially killed after 2, 4, 7, 14, 30, 60 and 100 days on this regimen, in each case 1 h after injection of bromodeoxyuridine (BrdU). In the HAQO/SBTI and SBTI alone groups, 2 days after the SBTI treatment the labeling indices of acinar cells were increased approximately 12- and 11-fold respectively, dropping rapidly thereafter and returning to the control value by day 30. The earliest eosinophilic foci were noted in the HAQO/SBTI group 60 days after HAQO initiation, with the component cells demonstrating markedly increased labeling indices in contrast to the completely normalized levels observed in the surrounding exocrine tissue. On the other hand, eosinophilic foci were scarcely induced in the HAQO or SBTI alone group throughout the experiment. These results thus indicate a clear temporal dissociation between initial proliferation in parenchymal pancreatic tissue caused by SBTI and subsequent development of eosinophilic foci in rats initiated with HAQO.

4-Hydroxyaminoquinoline-1-oxide↗

PubMed1993

K-ras mutations are frequent in pulmonary squamous cell carcinomas but not in adenocarcinomas of WBN/Kob rats induced by N-nitrosobis(2-oxopropyl)amine.

Pulmonary carcinomas induced by N-nitrosobis(2-oxopropyl) amine (BOP) in WBN/Kob rats were screened for point mutations in the K-ras protooncogene. Exons 1 and 2 were polymerase chain reaction amplified from paraffin-embedded sections, followed by direct DNA sequencing. G --> A transition mutations in the second base of codon 12 of the K-ras gene were found in 6/24 (25%) rat lung tumors induced by BOP. The incidence of point mutations was significantly higher (P < 0.005) in squamous cell carcinomas (5/7; 71%) than in adenocarcinomas (1/17; 6%), suggesting that the mutational activation of K-ras is associated with a differential growth advantage in these two histologically distinct types of lung tumors in rats. No mutations were found in codons 13, 61 or adjacent regions of these codons.

Adenocarcinoma↗

PubMed1993

Relationship between heat shock protein induction and the binding of antibodies to the extractable nuclear antigens on cultured human keratinocytes.

The importance of environmental factors such as ultraviolet light and temperature in the pathogenesis of cutaneous lupus erythematosus is well recognized. Recent evidence suggests the presence of autoantibodies to heat shock proteins (HSP) in the sera and enhanced expression of the HSP70 gene in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. We designed experiments to determine how HSP or stress protein inducers affect the cell surface binding of IgG antibodies from sera containing anti-SS-A/Ro and anti-ribonuclear protein (RNP) antibodies to keratinocytes because these antibodies are considered to be one of the immunologic triggers of cutaneous lupus erythematosus. Immunofluorescence and immunoblot analysis using a monoclonal antibody to the 72 kDa of HSP revealed that an 18-h incubation with 10 micrograms/ml of delta 12-PGJ2, one of cytotoxic prostaglandins, induced HSP72 formation in cultured human keratinocytes. delta 12-PGJ2 augmented the binding of IgG antibodies from sera containing anti-U1RNP and anti-SS-A/Ro antibodies to cultured keratinocytes, but produced no enhancement of the binding of IgG antibodies from sera containing anti-Sm or anti-DNA antibodies. Similar results were also obtained by using flow cytometry analysis. HSP was also induced by ultraviolet B irradiation. These results suggest that exposure of keratinocytes to stressors such as delta 12-PGJ2 and ultraviolet light increases the binding sites for U1RNP,SS-A/Ro, and SS-B/La antibodies. The association between HSP induction and the appearance of extractable nuclear antigens may provide a better understanding of why environmental stimuli can promote the development of erythematous lesions in the skin.

Antigens, Nuclear↗

PubMed1993

[Effects of cyclophosphamide on spontaneous testicular and pancreatic lesions in WBN/Kob rats].

This study was undertaken to investigate the effects of cyclophosphamide (CP) on spontaneous pancreatitis and testicular atrophy of WBN/Kob rats. CP was given daily in drinking water to groups of 20 male 6-week-old WBN/Kob rats at doses of 0 (control), 1.25 or 2.5 mg/kg for 20 weeks. The final body weight in the 2.5 mg/kg CP group was significantly lower than that in the control group. There were no significant differences in blood glucose levels and weights of the pancreas and testis between groups. On histopathological examinations, pancreatitis and testicular atrophy were noted in each group. However, the incidence of pancreatitis characterized by inflammatory cell infiltration and fibrosis in the 2.5 mg/kg CP group was significantly decreased as compared to the control group. In contrast, testicular atrophy was more severe in the 2.5 mg/kg CP group than in the control group. Thus the results demonstrated that CP has inhibitory effects on the development of pancreatitis and enhancing effects on the development of testicular atrophy in WBN/Kob rats.

Administration, Oral↗