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Biomedical subjects

J Koyama

Publications and source records attributed to J Koyama.

At least 55 records · Page 3Linked to original sources
PubMed1999

Clinical characteristics of aged Becker muscular dystrophy patients with onset after 30 years.

To elucidate the clinical characteristics of aged patients with Becker muscular dystrophy (BMD), 4 patients with this disease who were over 50 years were examined. The ages at onset in all patients were later than 30 years. All were proven to have a deletion around exons 45-55 of the Duchenne muscular dystrophy (DMD) gene. Two patients became wheelchair bound in their 40s or beyond, while the other 2 (aged 73 and 69, respectively) were still able to walk at the time of examination. Three of 4 patients had no obvious hypertrophy in their calves, which is known to be one of the characteristic clinical features in the juvenile BMD patients. Serum creatine kinase levels were elevated in all patients, but not markedly (mean 444.8 +/- 230.3 U/l; normal value < 180 U/l). Dilated cardiomyopathy was clinically apparent in 2 patients. We emphasize that some BMD patients are free of muscular symptoms until their 50s and are still self-supporting in their 60s or 70s.

Age of Onset↗
PubMed1998

Loss of water from the stratum corneum induces epidermal DNA synthesis in hairless mice.

Many clinical studies have shown that low humidity has a deleterious effect on skin, but the mechanisms involved are poorly understood. To clarify the changes that occur in skin, we examined epidermal cell proliferation in mice kept in a dry (relative humidity < 10%) or a moist (relative humidity > 90%) environment. In animals exposed to low humidity, epidermal DNA synthesis started to increase within 12 h, reaching twice the original level, and the increased level was maintained for up to 5 days. The transepidermal water loss (TEWL) of mice kept for 12 h in the dry environment was the same as that of mice kept in the moist environment, but the skin conductance was lower. The increase in epidermal DNA synthesis following exposure to the dry environment was inhibited by topical application of petrolatum. It is concluded that loss of water from the stratum corneum induces epidermal cell proliferation within 12 h, and this change occurs in the absence of apparent cutaneous barrier dysfunction.

Animals↗
PubMed1998

Inhibitory effect of furanonaphthoquinone derivatives on the replication of Japanese encephalitis virus.

Japanese encephalitis still occurs in endemic and epidemic forms over a wide area of Asia. Although the vaccine against Japanese encephalitis virus (JEV) is widely used, no antiviral drug has been reported. We used several different kinds of furanonaphthoquinone derivatives and found antiviral activity against JEV. Especially, 2-methylnaphtho[2,3-b]furan-4,9-dione (FNQ3) indicated the highest antiviral activity, followed by 2-(1-hydroxyethyl)-, 5(or 8)-hydroxy-, and 2-methyl-5(or 8)-hydroxy-analogs of naphtho[2,3-b]furan-4,9-dione. In the presence of 3 microg/ml FNQ3, the virus yields in Vero cells were 2 x 10(5) PFU/ml at 24 h after infecting with the virus and 10% of the control level. Western blot analysis using anti-E rabbit sera or anti-NS3 showed that the expression of viral proteins was inhibited by treatment with FNQ3. In addition, Northern blot analysis indicated that the appearance of JEV-RNA was also inhibited by FNQ3. These results suggest that FNQ3 inhibits JEV replication through viral RNA and protein synthesis.

Animals↗
PubMed1998

Dry condition affects desquamation of stratum corneum in vivo.

We examined whether a dry condition actually induces scaly skin in vivo. Hairless mice were kept in a high humidity condition or a low humidity condition and skin changes were examined. Scales appeared on the backs of mice kept for 3 days under the dry condition. The weight of stratum corneum (SC) was increased at this point, and these alterations were not accompanied with hyperproliferation of the nucleated cell layer of the epidermis. A decrease of desmosomal degradation was observed, though, desquamation-related enzyme activity was not altered. The regulation mechanism of desquamation is not yet clear, however, in vitro experiments suggest that the water content in SC is an important factor. The water content of SC was decreased in the dry condition. These results indicate that a dry environment perturbs desmosome degradation in intact SC by decreasing the water content of SC, and the consequent impairment of desquamation in normal skin in vivo may lead to the induction of a scaly skin surface.

Animals↗
PubMed1998

Gas in the temporomandibular joint: computed tomography findings. Report of 3 cases.

In each of 3 patients referred for computed tomographic examinations of the temporomandibular joint, a gas collection was observed in the inferior space of the joint. The gas was observed on the posterosuperior surface of the mandibular condyle in the open mouth position in each patient. Each of 2 patients had saucer-shaped bone resorption of the mandibular condyle adjacent to the gas; 1 patient had no remarkable bone abnormality. A history of temporomandibular joint puncture or facial trauma was denied by all 3 patients.

Adult↗
PubMed1998

Immobilization-induced and crowded environment-induced stress delay barrier recovery in murine skin.

To examine the effect of stress on skin homeostasis, cutaneous barrier recovery was measured in rate exposed to immobilization stress after tape stripping or sodium dodecyl sulphate treatment. The barrier function was evaluated by measuring transepidermal water loss. Barrier recovery was delayed in rats exposed to stress in comparison with untreated controls. This tendency was observed in both male and female animals. The delay in barrier recovery was blocked by application of the sedative drugs diazepam and chlorpromazine. The barrier recovery rate in mice which were kept at a high population density (10 animals per cage) for 2 weeks was slower than that in mice kept at lower population densities (five animals or one animal per cage). These animal models could be useful for objectively quantifying the influence of stress on the cutaneous function.

Animals↗
PubMed1998

Cholesterol sulfate inhibits proteases that are involved in desquamation of stratum corneum.

We previously reported that desmosomes play a key role in the adhesion of corneocytes, and their digestion by two types of serine proteases leads to desquamation. Patients with recessive X-linked ichthyosis show hyperkeratosis attributable to desmosomes, associated with an increased content of cholesterol sulfate (CS) and an increased thickness of stratum corneum. In this study, therefore, we examined the possibility that CS provokes the abnormal desquamation, acting as a protease inhibitor. Scaling was induced on mice after topical application of chymostatin and leupeptin. Visible scale was also observed on mice after topical application of CS. We found that the stratum corneum thickness of CS-treated mice was increased in comparison with that of vehicle-treated mice. The thickness of the epidermis and the labeling index with proliferating cell nuclear antigen from CS-treated mice was almost the same as that from vehicle-treated mice. Moreover, in the stratum corneum of CS-treated mice, the content of desmosomes was higher than that in vehicle-treated mice. CS also inhibited the protease-induced cell dissociation of human stratum corneum sheets. In vitro, CS competitively inhibited both types of serine protease: the Ki for trypsin was 5.5 x 10(-6) M and that for chymotrypsin was 2.1 x 10(-6) M. These results indicate that CS retards desquamation by acting as a protease inhibitor. Thus, accumulation of stratum corneum in recessive X-linked ichthyosis may be a result of the inhibition by excessive CS of proteases involved in the dissolution of desmosomes, required for desquamation of the stratum corneum.

Animals↗
PubMed1998

Exposure to a dry environment enhances epidermal permeability barrier function.

Previous studies have suggested that transepidermal water movement may play an important role in epidermal homeostasis and barrier repair. Here we analyzed cutaneous barrier function, epidermal morphology, and lipid content of the stratum corneum in hairless mice maintained in a high relative humidity (RH > 80%) versus low humidity (RH < 10%) environment for 2 wk. Basal transepidermal water loss was reduced by 31% in animals maintained in a dry versus humid environment. Moreover, the number of lamellar bodies in stratum granulosum cells, the extent of lamellar body exocytosis, and the number of layers of stratum corneum increased in animals kept in a dry environment. Furthermore, the dry weight of the stratum corneum and the thickness of the epidermis also increased in a dry environment. In addition, total stratum corneum lipids increased but lipid analysis revealed no significant differences in lipid distribution. Lastly, barrier recovery following either acetone treatment or tape stripping was accelerated after prolonged prior exposure to a dry environment, while conversely, it was delayed by prior exposure to a humid environment. These studies demonstrate that environmental conditions markedly influence epidermal structure and function, and suggest mechanisms by which the environment could induce or exacerbate various cutaneous disorders.

Animals↗
PubMed1998

Antimicrobial activity of novel furanonaphthoquinone analogs.

Analogs of furanonaphthoquinone (FNQ) from Tecoma ipe Mart had MICs ranging from 1.56 to 25 microg/ml against gram-positive bacteria. FNQ showed significantly lower MICs against methicillin-resistant Staphylococcus aureus than against methicillin-sensitive S. aureus. FNQ inhibited Helicobacter pylori with an MIC of 0.1 microg/ml. Fungi, including pathogenic species, were sensitive to FNQ with MICs similar to those of amphotericin B.

Aspergillus↗
PubMed1998

Modification of LC phenotype and suppression of contact hypersensitivity response by stress.

BACKGROUND: Stress is thought to exacerbate a number of diseases, some of which are skin disorders. Epidermal Langerhans' cells play a major role in cutaneous immune reactions. OBJECTIVE: The effects of two types of stress on the cutaneous immune system were to be assessed in mice. METHODS: Mice received stress by immobilization or housing at various population densities. Epidermal sheets were stained for I-A molecules (a member of class II major histocompatibility complex) and analyzed with a confocal-laser- scanning microscope. Contact hypersensitivity reaction to 2,4,6-trinitrochlorobenzene was elicited in mouse ears. RESULTS: The cell density, intensity of I-A expression, and number of dendrites were decreased as the population density increased. Elicitation of contact hypersensitivity was suppressed in mice that received either population or immobilization stress. Increased I-A expression and number of dendrites were observed in adrenalectomized compared to sham-operated mice. The population-dependent suppression of contact hypersensitivity reaction was not observed in adrenalectomized mice. After incubation with serum from mice that received either immobilization stress or population stress, the expression of I-A molecules on a XS52 Langerhans' cell-like cell line was reduced. CONCLUSION: Stress affected the cutaneous immune system. There were indications that adrenergic hormones played a role in the regulation of the system.

Adrenalectomy↗
PubMed1998

Efficacy of a low-dose subcutaneous lisuride infusion in Parkinson's disease.

Five parkinsonian patients with motor fluctuations and dyskinesia after long-term treatment with levodopa were treated with subcutaneous lisuride infusion (0.24-0.42 mg/day) together with oral levodopa for a mean period of 27 (range 13-36) months. All 5 patients showed marked initial improvement in mobility. Mild psychiatric side effects were observed in three patients; however, these side effects disappeared with reduction in the dosage of lisuride to 0.06 mg per day without a significant increase in motor fluctuations. A low dose of subcutaneous lisuride infusion with oral levodopa is an effective treatment for fluctuations of motor performance in parkinsonian patients without adverse psychiatric effects.

Administration, Oral↗
PubMed1997

Modulatory effect of L-NAME, a specific nitric oxide synthase (NOS) inhibitor, on stress-induced changes in plasma adrenocorticotropic hormone (ACTH) and corticosterone levels in rats: physiological significance of stress-induced NOS activation in hypothalamic-pituitary-adrenal axis.

We investigated whether NG-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of nitric oxide synthase (NOS), can modify the stress-induced adrenocorticotropic hormone (ACTH) and corticosterone responses, because we found that immobilization-induced stress increases NOS mRNA and protein levels and enzyme activity in the adrenal cortex. The physiological significance of these phenomena, however, remains unknown. Plasma ACTH and corticosterone levels were determined by radioimmunoassay (RIA) of systemic blood samples and NOS enzyme activity was measured as the rate of [3H]arginine conversion to [3H]citrulline in the presence of tissue homogenate of adrenal cortex separated from the adrenal gland. The NOS enzyme activity in the adrenal cortex of rats pre-injected with saline at 2 h after the 2-h immobilization was significantly higher (P < 0.01) than that in the non-stressed controls. Pre-injection of L-NAME (100 mg/kg, s.c.) almost completely abolished the activity. This dose of L-NAME maintained a significantly elevated plasma corticosterone level (P < 0.05, compared with basal level) even 2 h after the 2-h stress, whereas the plasma corticosterone level in rats pre-injected with saline returned to the basal level at the same time point. Plasma ACTH level in L-NAME-pre-treated rats was higher than that in those pre-treated with saline 2 h after the stress, but the difference was not significant. This dose of L-NAME did not influence plasma ACTH or corticosterone levels under resting conditions without stress. These findings suggest that the stress-induced increase in NO synthesis in the adrenal cortex can modify the stress-induced corticosterone response to facilitate the recovery from the elevated corticosterone secretion by stress in the adrenal cortex to the resting basal level.

Adrenocorticotropic Hormone↗
PubMed1997

Inhibitory effects on Epstein-Barr virus activation of anthraquinones: correlation with redox potentials.

The redox potentials have been determined for nine anthraquinones in phosphate buffer at pH 7.2 by means of cyclic voltammetry. A definite correlation has been found between the redox potentials and the inhibitory effects of the anthraquinones on the EBV-EA activation. It has further been shown that the correlation can be made better by introducing an electronic property, i.e. the atomic charge at O12 as an additional parameter.

Anthraquinones↗
PubMed1997

Anti-tumor promoting effects of naphthoquinone derivatives on short term Epstein-Barr early antigen activation assay and in mouse skin carcinogenesis.

In continuation of our studies of natural and synthetic products as cancer chemopreventive agents, we have examined a number of naphthoquinone derivatives including monomeric, dimeric and tetrameric naphthaquinones occurring in the Diospyros and other selected plant genera. Several synthetic naphthoquinones were also evaluated. Initially these compounds were tested for in vitro anti-tumor promoting effect on Epstein-Barr virus early antigen activation produced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and thereafter in in vivo on two-stage mouse skin carcinogenesis. Our studies show some of these compounds have potent anti-tumor promoting activity.

Animals↗
PubMed1997

Antitumor agents--CLXVII. Synthesis and structure-activity correlations of the cytotoxic anthraquinone 1,4-bis-(2,3-epoxypropylamino)-9,10-anthracenedione, and of related compounds.

1,4-Bis-(2,3-epoxypropylamino)-9,10-anthracenedione (3) was synthesized in this laboratory and was found to be a potent antitumor agent. Derivatives of this compound containing anthraquinone, naphthoquinone, and quinone skeletons were also prepared and evaluated for in vitro cytotoxic activity in several cell lines. These molecules were designed as bifunctional antitumor agents with the potential to act as (1) intercalating agents due to their planar backbones, and (2) alkylating agents due to the presence of alkylating moieties in their side chains. Compounds with an anthraquinone skeleton and propylamino side chains containing epoxides or halohydrins as the alkylating species showed greater activity than similar compounds with naphthoquinone or quinone skeletons. Compounds without these alkylating functionalities (e.g., with alkene or amino groups) were generally inactive. Hydroxy substitution on the planar skeleton in conjunction with alkylating side chains gave compounds with the most potent cytotoxic activity. The position of the hydroxy groups and side chains could be varied without substantially affecting activity. Activity was retained when an epoxypropyloxy side chain was substituted for the epoxypropylamino side chain in the parent compound.

Animals↗
PubMed1997

Mitochondrial damage by a new antitumour agent furanonaphthoquinone derivative in human cervical cancer HeLa cells.

The intracellular ultrastructural changes induced by the new antitumour agent 2-methylnaphtho[2,3-b]furan-4,9-dione (FNQ3) were investigated in human cervical cancer HeLa cells in comparison with normal cervix cells. The normal cells were isolated from cervixes surgically resected from myoma patients and were keratin positive. FNQ3 at 3-5 micrograms ml-1 selectively damaged the HeLa cell mitochondria followed by rough-surfaced endoplasmic reticulum resulting in cell death. In contrast, normal cells remained unaffected at that concentration but were damaged by 20 micrograms ml-1 FNQ3. The FNQ3-induced tumour cell toxicity was inhibited 52% and 36% by trolox and a water-soluble fraction of the antioxidative substance AOB, respectively. The results indicated that FNQ3 is selectively toxic to HeLa cells at approximately eight times that of normal cells in terms of mitochondrial alteration and free radical formation.

Antineoplastic Agents, Phytogenic↗