Biomedical subjects

F Furukawa

Publications and source records attributed to F Furukawa.

At least 127 records · Page 7Linked to original sources

PubMed1996

Chemopreventive effects of 3-phenylpropyl isothiocyanate on hamster lung tumorigenesis initiated with N-nitrosobis(2-oxopropyl)amine.

The chemopreventive effects of 3-phenylpropyl isothiocyanate (PPITC) were investigated in N-nitrosobis(2-oxopropyl)amine (BOP)-initiated hamsters. A total of 120 female 5-week-old hamsters were divided into 6 groups. Animals in groups 1-3, each consisting of 30 hamsters, were twice sc injected 7 days apart as an initiation treatment. Hamsters in groups 1 and 2 were respectively given 100 microM and 10 microM of PPITC by gavage 2 h prior to each BOP treatment. Animals in group 3 were treated with BOP alone, serving as an initiation-positive control. Animals in groups 4-6, each consisting of 10 hamsters, were given 100 microM or 10microM of PPITC alone, or non-treated, thus being available as matched negative controls to groups 1-3. At termination (experimental week 51 after the first BOP injection), the incidences of lung adenomas and/or adenocarcinomas were significantly decreased in groups 1 and 2 as compared to the group 3 value (p<0.01). The combined lung tumor incidences were inhibited by 94% and 59% at 100 and 10 microM doses, respectively. The inhibitory effects of PPITC were thus dose-dependent. The data for multiplicity of lung tumors dramatically illustrated the inhibitory effects of PPITC, and there were also statistically significant differences in the chemopreventive effect between 100 microM and 10 microM PPITC treatments. On the other hand, the PPITC treatments did not significantly modulate the development of neoplastic lesions in the pancreas,liver and kidney, although the treatments did show inhibitory tendencies, except on the liver lesions. Under present experimental conditions, PPITC itself did not exhibit tumorigenicity or apparent toxicity. The results in the present study thus clearly indicate that PPITC has an effective chemopreventive action on BOP-induced lung tumorigenesis in hamsters.

Animals↗

PubMed1996

Photohaptenic properties of fluoroquinolones.

Although quinolone antibacterial agents have both phototoxicity and photoallergenicity, the latter's potency has been poorly investigated compared with the former's. Some of the photoallergic chemicals serve as photohaptens, which lead to T-cell-mediated immune reactions after photobinding to protein by UVA radiation. We examined the photohaptenic potential of fluoroquinolones, including lomefloxacin (LFLX), ciplofloxacin, norfloxacin, ofloxacin, levofloxacin, fleroxacin, enoxacin and sparfloxacin (SPFX). The absorption spectra of the quinolones were altered by UVA irradiation, with an exception of SPFX that seems to be photostable toward UVA. Bovine serum albumin and murine epidermal cells were coupled with these fluoroquinolones other than SPFX by exposure to UVA. Subcutaneous inoculation of fluoroquinolone-photomodified epidermal cells induced and elicited a delayed-type hypersensitivity reaction in mice. However, epidermal cells incubated with LFLX without UVA exposure also induced and elicited a significant hypersensitivity reaction to a lesser degree than LFLX-photomodified epidermal cells. Furthermore, there was cross-reactivity between LFLX-photomodified epidermal cells and simply LFLX-incubated cells. This suggests that cells can be weakly modified with LFLX even in the dark and that UVA irradiation promotes this modification. Our study demonstrated that fluoroquinolones have photohaptenic properties to which their photoallergenicity is probably ascribed.

Animals↗

PubMed1996

The macrolide antibiotic, roxithromycin suppresses IFN-gamma-mediated immunological functions of cultured normal human keratinocytes.

The effects of the macrolide antibiotic, roxithromycin (RXM) on immunological functions of cultured normal human keratinocytes (NHK) were studied. RXM neither modulated the expression of intercellular adhesion molecule-1 (ICAM-1) and human histocompatibility leukocyte antigen (HLA)-DR nor mobilized intracellular free calcium in NHK that were cultured in medium alone. However, the ICAM-1 and HLA-DR expression induced by cultivation with interferon-gamma (IFN-gamma) was upregulated and suppressed, respectively, by pretreatment of NHK with RXM. Whereas ICAM-1 upregulation was observed with RXM at a concentration as high as 0.1 mM, the inhibition of HLA-DR expression by RXM was virtually dose-dependent at doses ranging from 100 nM to 0.1 mM. Accessory cell function of major histocompatibility complex (MHC) class II-bearing NHK in terms of the T-cell response to staphylococcal enterotoxin B was suppressed by pretreatment of NHK with RXM, indicating the functional consequence of RXM-induced reduction of MHC class II molecules. Furthermore, RXM inhibited IFN-gamma-mediated upregulation of IL-1 alpha secretion by NHK. These results show that RXM suppresses immunological functions of keratinocytes triggered by IFN-gamma and suggest the therapeutic relevance of RXM to T cell-mediated inflammatory skin diseases and T cell malignancies such as atopic dermatitis, psoriasis and cutaneous T cell lymphoma, which can be exacerbated by keratinocytes immunologically modulated by exposure to IFN-gamma.

Animals↗

PubMed1996

Eosinophilic pustular folliculitis effectively treated with recombinant interferon-gamma: suppression of mRNA expression of interleukin 5 in peripheral blood mononuclear cells.

Eosinophilic pustular folliculitis (EPF) is characterized clinically by pruritic grouped follicular papules and pustules on the trunk, limbs, and face, and, histologically, by follicular infiltration with eosinophils. The blood eosinophil count is elevated in most patients. Oral minocycline, nonsteroidal anti-inflammatory drugs, diaminodiphenylsulphone, and corticosteroids may induce remission. We report two Japanese men with EPF who responded poorly to the usual therapy. Intravenous injections of recombinant interferon-gamma (rIFN-gamma), 5 x 10(5) to 2 x 10(6) Japan Reference Unit (JRU) (1 JRU roughly corresponds to 4 NIH units) daily for 7 days, cleared the skin lesions and returned the peripheral eosinophil counts to normal in both patients. However, the lesions recurred 2-3 days after rIFN-gamma was stopped. Both patients have received intravenous rIFN-gamma once or twice a week for nearly 1 year without systemic side-effects. Reverse transcriptase-polymerase chain reaction revealed a decreased expression of interleukin 5 (IL-5) mRNA in peripheral mononuclear cells after the rIFN-gamma therapy. rIFN-gamma may become the treatment of choice in recalcitrant EPF, although further studies are needed. It may work by interfering with the immunological function of type 2 T-helper cells, including IL-5 production responsible for the growth and differentiation of eosinophils.

Adult↗

PubMed1996

[A 13-week subchronic toxicity study of gardenia blue in F344 rats].

A 13-week oral toxicity study of gardenia blue was performed in male and female F344 rats at the dose levels of 5.0, 2.5, 1.25, 0.6 and 0% in the diet, to determine the maximum tolerable dose (MTD) for subsequent investigation of carcinogenicity. Rats were randomly allocated to 5 groups, each consisting of 10 males and 10 females. No groups showed decreases in body weight gain and food intake, and all animals survived until the end of the experiment. A dose-dependent decrease in number of platelets was observed in females treated with gardenia blue in hematological examination, but not in males. No histopathological change, relating to the treatment, in megakaryocyte which is the progenitor cell of platelets was observed in the treated-females. Serum biochemistry revealed increases in GOT and GPT in both sexes treated with the 5.0% and 2.5% gardenia blue, as compared to the control value. However, these were not considered to be specific changes because of lack of any clear dose response. In addition, no histopathological changes indicating obvious toxicity of gardenia blue were observed in the liver of both sexes treated with gardenia blue. Based on these data, the MTD of gardenia blue for both sexes in F344 rats was considered to be 5.0% or more in the diet.

Alanine Transaminase↗

PubMed1995

Enhancement of GST-P positive liver cell foci development by a medium-term carcinogenicity bioassay using repeated administration of D-galactosamine.

This study was performed for developing a new medium-term carcinogenicity bioassay treated with D-galactosamine (DGA) as a non-surgical method without partial hepatectomy (PH). In male F344 rats initiated with diethylnitrosamine (DEN, 200 mg/kg i.p.), enhancing effects of DGA (300 mg/kg i.p.) given twice 3 weeks apart during the promotion procedure with 2-acetylaminofluorene (2-AAF, 0.01% in diet) were compared along with those of PH by analyzing preneoplastic glutathione S-transferase placental form positive (GST-P+) hepatocyte foci as endpoint marker lesions. The DGA treatment did not affect the body weight gain whereas the PH treatment caused a transient body weight loss. Although both bioassay protocols were effective to detect the potential hepatocarcinogenicity of 2-AAF, the number and area of GST-P positive foci per cm2 were larger in the bioassay using DGA than in that using PH, the number being statistically significant (P < 0.05). Our results thus suggest that the present bioassay protocol with repeated administration of DGA instead of PH may offer a new and sensitive method to screen large numbers of environmental carcinogens.

2-Acetylaminofluorene↗

PubMed1995

Dose-dependent promotion effects of potassium chloride on glandular stomach carcinogenesis in rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine and the synergistic influence with sodium chloride.

The modifying effects of potassium chloride (KCl) ingestion on glandular stomach carcinogenesis were investigated in male Wistar rats induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and were compared with those of sodium chloride (NaCl). A total of 120 male 6-week-old Wistar rats were divided into six groups, each consisting of 20 animals. After initiation of treatment with a MNNG solution (100 parts/million) as their drinking water for 10 weeks, rats were fed a diet supplemented with 5% NaCl, 2.5% NaCl, 2.5% NaCl plus 2.5% KCl, 5% KCl, 2.5% KCl, or a basal diet alone for the following 62 weeks. Under this experimental condition, there were no statistical differences in the final body weights between groups. The incidences of adenocarcinomas in the glandular stomachs were significantly higher in the 5% NaCl and combined 2.5% NaCl-plus-2.5% KCl groups (P < 0.05 and 0.01) than in the MNNG alone (control) group. The incidences of atypical or precancerous hyperplasias in the glandular stomachs were increased significantly by the 5% NaCl, 2.5% NaCl-plus-2.5% KCl, and 5% KCl treatments (P < 0.05 or 0.01). The multiplicities of adenocarcinomas were significantly greater in the 5% NaCl, 2.5% NaCl, and combined NaCl-plus-KCl groups (P < 0.05 or 0.01) compared with the control value. The multiplicity data for atypical hyperplasias were most striking; namely, their multiplicities were increased significantly by the treatments of NaCl or KCl (P , 0.01) in a clear dose-dependent manner and enhanced synergistically by the combined treatment of NaCl and KCl. Because the concentrations of KCl used in this study were about 1.3 times lower than those of NaCl on a molar basis, although the doses of each chemical were exactly the same on a weight-percent basis, it is suggested that the enhancing effects of KCl might not be much different from those of NaCl. The results in the present study thus indicate that, similarly to NaCl, KCl ingestion exerts dose-dependent promoting effects and a synergistic influence with NaCl when given during the postinitiation phase of two-stage glandular stomach carcinogenesis in rats.

Animals↗

PubMed1995

Susceptible responsiveness to bacterial superantigens in peripheral blood mononuclear cells from patients with psoriasis.

We investigated the in vitro responses to bacterial superantigens of peripheral blood mononuclear cells taken from patients with psoriasis (one arthropathic, two guttate and four chronic plaque type). We also analysed the relationship between the magnitude of the responses of peripheral blood mononuclear cells to bacterial exotoxins and the number of circulating T cells bearing V beta 2 and V beta 3 regions. The proliferative response of peripheral blood mononuclear cells to Staphylococcal enterotoxin B and toxic shock syndrome toxin-1 was significantly higher in patients with active psoriasis than in normal subjects. An improvement in skin eruption was associated with a decrease in the lymphocyte response to one-half or one-third that of the active phase. There was no significant difference between patients with psoriasis and normal subjects in the percentage of V beta 2- and V beta 3-positive circulating T cells. The percentages of V beta 2-positive and V beta 3-positive cells were not correlated with the levels of responsiveness to toxic shock syndrome toxin-1 and to Staphylococcal enterotoxin B, respectively. These findings suggest that the magnitude of responses of peripheral blood mononuclear cells to bacterial toxins does not depend on the number of T cells reactive with the relevant superantigen, but depends on the extent of skin lesions in psoriasis.

Adult↗

PubMed1995

FK506: therapeutic effects on lupus dermatoses in autoimmune-prone MRL/Mp-lpr/lpr mice.

The effects of FK506, a new immunosuppressive agent, on the development of lupus dermatoses were investigated in the autoimmune-prone MRL/Mp-lpr/lpr (MRL/lpr) mouse, which is an animal model for the spontaneous development of skin lesions similar to those of human lupus erythematosus (LE). FK506 reduced the incidence of skin lesions, lupus nephritis, the titre of serum anti-double-stranded DNA antibodies and the massive T cell proliferation. The incidence and magnitude of IgG deposition at the dermoepidermal junction were not changed. These results suggest that FK506 is a promising immunosuppressive agent for the control of autoimmune skin diseases.

Animals↗

PubMed1995

Effect of cigarette smoke on the mutagenic activation of various carcinogens in hamster.

Male Syrian golden hamsters were exposed for 1 or 2 weeks to smoke produced by commercial non-filter cigarettes for 5 consecutive days in a Hamburg type II smoking machine. Postmitochondrial fractions (S9) prepared from the liver, lungs, and pancreas were used in the Ames liquid incubation assay, in order to assess the effect of cigarette smoke (CS) on the metabolic activation of four groups of procarcinogens. The mutagenic activities of five heterocyclic amines on strain TA98 in the presence of liver S9 mix were induced up to 3.7 times above controls including sham smoke control, while no significant alteration of mutagenicity was observed with 3'-hydroxymethyl-N,N-dimethyl-4-aminoazobenzene and benzo[a]pyrene on TA98 or with N-nirosobis(2-oxopropyl)amine (BOP) on TA100. A similar stimulation of metabolic activation was also observed for 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) with S9 from the lungs but not from the pancreas. The mutagenic potential of 11 carcinogens including aflatoxin B1 (AFB1) and two other heterocyclic amines was also examined using liver S9 from male hamsters pretreated with phenobarbital (PB) or 3-methylcholanthrene (MC). The numbers of revertant colonies were much higher (2-20-fold) in the presence of MC-treated liver S9 than in the presence of PB-treated liver S9, except in the case of AFB1 which showed a higher mutagenicity with PB-induced S9. 7,8-Benzoflavone considerably inhibited the activities of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and Trp-P-1 in the presence of either untreated, MC- or CS-treated liver S9, whereas metyrapone was totally lacking this effect, indicating that cytochrome P450(CYP)1A1/1A2 isoforms of hamster liver are predominantly involved in the metabolic activation of these carcinogens. CS exposure of hamsters might selectively induce hepatic CYP1A2 which cannot activate BOP. Consequently, the present findings could explain, in part, the anticarcinogenic effect of CS on BOP-induced pancreatic tumors in hamsters. The findings further support the idea that CS markedly stimulates the metabolic activation of food-derived carcinogens, which may contribute to the overall carcinogenic effects of cigarette smoking.

Animals↗

PubMed1995

Effects of caffeine on glandular stomach carcinogenesis induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride.

The modifying effects of caffeine ingestion on glandular stomach carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium chloride (NaCl) were investigated in male Wistar rats. Animals were given a MNNG solution (100 ppm) as their drinking water and simultaneously fed a diet supplemented with 5% NaCl for 8 wk. They then received 0.25% caffeine solution (groups 1 and 3) or tap water (groups 2 and 4) as the drinking water, and were fed the NaCl diet (groups 1 and 2) or basal diet (groups 3 and 4) for the following 32 wk. Both caffeine and NaCl treatments exerted growth retardation effects, the suppression being stronger with caffeine than NaCl, and animals in group 1 (NaCl plus caffeine) showing the lowest body weight. The incidence of adenocarcinomas in the pylorus was significantly decreased in group 1 compared with the group 2 (NaCl) value (P < 0.05). The incidence of atypical hyperplasias in the fundus was also lower in group 1 than in group 2, although in both cases significantly higher (P < 0.05 and P < 0.01) than in group 4 (no treatment). These results were in good agreement with short-term assay findings whereby lipid peroxidation in the glandular stomach mucosa induced by 4% NaCl ingestion was inhibited by caffeine treatment. In group 3 (caffeine), caffeine intake by itself did not modulate glandular stomach tumour development. The results thus suggest that caffeine inhibits the gastric tumour promotion activity of NaCl in rats.

Adenocarcinoma↗

PubMed1995

Staphylococcal enterotoxin B upregulates expression of ICAM-1 molecules on IFN-gamma-treated keratinocytes and keratinocyte cell lines.

The effects of staphylococcal enterotoxin B (SEB), a Staphylococcus aureus-derived bacterial superantigen, on expression of intercellular adhesion molecule-1 (ICAM-1) were examined in cultured normal and transformed (DJM-1 cells) human keratinocytes by flow cytometry, confocal microscopy, digital image processing, and reverse transcriptase-polymerase chain reaction. SEB significantly upregulated ICAM-1 expression in the interferon-gamma (IFN-gamma)-pretreated, HLA-DR-positive normal keratinocytes and DJM-1 cells in a dose-dependent manner, but not in the untreated, HLA-DR-negative cells. Other toxins such as diphtheria and pertussis toxins did not have the effect. The distribution of SEB and HLA-DR molecules was identical on the IFN-gamma-treated, HLA-DR-positive DJM-1 cells by confocal microscopy. Digital image processing analysis demonstrated that SEB induced a transient increase of intracellular calcium concentration only in the IFN-gamma-treated DJM-1 cells. Pretreatment of the IFN-gamma-treated DJM-1 cells with anti-major histocompatibility complex class II monoclonal antibody completely blocked the effect of SEB. Furthermore, ICAM-1 mRNA was detected in the IFN-gamma-pretreated, SEB-exposed normal keratinocytes by reverse transcriptase-polymerase chain reaction. Our results demonstrate that SEB binds to keratinocytes, presumably via major histocompatibility complex class II molecules such as HLA-DR, triggers calcium mobilization, and induces the synthesis of ICAM-1 molecules. We speculate that, in various cutaneous disorders, SEB penetrates the epidermis and interacts with HLA-DR-positive keratinocytes to upregulate ICAM-1 expression, thus modulating the course of the inflammatory process.

Antigen-Presenting Cells↗

PubMed1995

The effects of non-interval PUVA therapy on the plaque stage of mycosis fungoides.

The effectiveness of non-interval topical PUVA treatment was studied in four patients with mycosis fungoides at the plaque stage. Five regions of each patient were exposed to UVA immediately, 30 minutes, 60 minutes, 90 minutes, and 120 minutes, after topical application of 8-methoxypsoralen, respectively. The effects of these treatments were evaluated by clinical appearance and histological findings after the 20th treatment. All five regions were more improved clinically and histologically than the control region, which was not given PUVA therapy. There were no clear differences clinically among these five regions. Biopsy specimens from each region revealed the disappearance of epidermotropism and a marked decrease in atypical mononuclear cell infiltrations in the dermis. From these data, we concluded that there were no clear differences between these five treatments clinically or histologically and that non-interval PUVA therapy is useful for the early stages of mycosis fungoides. To our knowledge, this is the first report of non-interval PUVA therapy for mycosis fungoides.

Adult↗

PubMed1995

Soluble E-cadherin: a novel cutaneous disease marker.

E-cadherin is a major homophilic cell-cell adhesion molecule of the skin. There are two forms of E-cadherin--membrane and soluble types. Although various abnormalities of the former type have been identified in some cutaneous diseases, information relating to the latter is sparse. We measured the concentrations of soluble E-cadherin in several cutaneous diseases, and found higher levels in sera from patients with bullous pemphigoid, pemphigus vulgaris, psoriasis vulgaris and inflammatory skin diseases, compared with controls. In psoriasis vulgaris the levels of soluble E-cadherin in sera correlated with the PASI score. In normal individuals, levels in suction blister fluid were double those in sera. These findings suggest that changes occur in circulating levels of soluble E-cadherin in skin disease, possibly reflecting increased turnover and/or proteolysis of cell-surface molecules in the epidermis.

Biomarkers↗

PubMed1995

Cutaneous colonization with staphylococci influences the disease activity of Sézary syndrome: a potential role for bacterial superantigens.

It has previously been shown that circulating Sézary cells respond in vitro to superantigenic staphylococcal exotoxins in a manner that is restricted by their V beta usage. This study was conducted to examine whether cutaneous colonization with Staphylococcus aureus influences the activity of the skin lesions of Sézary syndrome, and whether S. aureus isolated from patients with Sézary syndrome stimulates circulating Sézary cells in vitro. Two patients with Sézary syndrome, whose skin was colonized with S. aureus, were treated with antibacterial agents, and the relation between the severity of the skin disease and the degree of S. aureus colonization was assessed. In addition, the patients' peripheral blood mononuclear cells were cultured in the presence of mitomycin C-treated S. aureus or superantigenic staphylococcal toxins. The antibacterial treatment improved the skin disease, and eliminated S. aureus in both patients. In one patient, 98% of the peripheral blood mononuclear cells bore V alpha 2V beta 17 of the T-cell receptor, indicative of the presence of an extremely high percentage of circulating Sézary cells. The peripheral blood lymphocytes from this patient responded well in vitro to superantigenic staphylococcal enterotoxin (SE), but not to SEA or toxic shock syndrome toxin-1, or to mitomycin-treated S. aureus isolated from the same patient. Cutaneous colonization by S. aureus influences the disease activity of CTCL, possibly by activation of Sézary cells by bacterial superantigenic exoproteins.

Aged↗

PubMed1995

Focal dermal hypoplasia (Goltz syndrome) associated with multiple giant papillomas.

We report a case of focal dermal hypoplasia (FDH) with multiple giant papillomas on nonperimucosal areas. The patient had had cribriform hyperpigmented and depigmented plaques on the trunk and extremities since birth. There were also hypoplastic skin lesions on the right arm, left elbow and right thigh. The multiple giant papillomas began to appear, when she was 22 years old, on the trunk and extremities. Cryotherapy was effective in controlling them.

Adult↗

PubMed1995

Cell proliferation in lung fibrosis-associated hyperplastic lesions.

1. Cell proliferative activity of atypical bronchioalveolar epithelia in lung fibrosis cases treated with bleomycin (BLM) or radiation was investigated by studying the histochemistry of the argyrophil nucleolar organiser regions (AgNORs) and proliferating cell nuclear antigen (PCNA). 2. Five and 14 autopsy cases of individuals who died of pulmonary fibrosis, caused by BLM treatment and irradiation respectively, were compared with (i) six control subjects who proved to have no apparent fibrosis of the lung at autopsy and (ii) four lung squamous cell carcinoma cases. 3. Histopathologically, both the BLM-treated and irradiated cases showed extensive collapse of the lung caused by severe fibrosis, although proliferative epithelial lesions such as atypical bronchioloalveolar hyperplasia and squamous metaplasia were more prominent in the former. 4. The mean AgNOR numbers in both atypical hyperplasias and metaplasias, of either BLM or irradiation cases, were significantly higher than in control bronchioalveolar epithelial areas, whereas they were lower than in the lung cancers. Data for PCNA-labelling indices were in time with those for AgNORs. 5. The results indicate that atypical hyperplastic lesions in the bronchioloalveoli arising during the fibrosing process as induced by BLM, and by irradiation, are highly proliferative.

Adult↗

PubMed1995

[A 13-week subchronic toxicity study of josamycin in F344 rats].

A 13-week subchronic toxicity study of josamycin was performed in male and female F344 rats to determine the maximum tolerable dose (MTD) for subsequent investigation of the carcinogenicity. As animals refused to take diet containing 5.0% josamycin in our preliminary study, dose levels in the present study were determined as 0, 0.16, 0.32, 0.63, 125 and 2.5% in diet. Rats were randomly allocated to 6 groups, each consisting of 10 males and 10 females. No animal died during the administration period and no group showed significant changes in body weight gain. Definite toxicity of josamycin was not noted in hematological and serum biochemical examinations. Histopathological examinations revealed no particular findings related to josamycin administration except cecal enlargement in the 1.25 and 2.5% groups. based on the results of the present study, it was concluded that the MTD of josamycin in 2.5% in diet, because the dietary dose level of 2.5% proved to exert no significant toxicological signs.

Administration, Oral↗