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Biomedical subjects

S Moriwaki

Publications and source records attributed to S Moriwaki.

At least 19 recordsLinked to original sources

Convulsive episodes in patients with group A xeroderma pigmentosum.

OBJECTIVES: To clarify the incidence of convulsive episodes in patients with group A xeroderma pigmentosum (XPA). MATERIALS AND METHODS: By investigating the history of convulsive episodes of our 33 XPA patients through either their medical charts or direct interviews with their caretakers. RESULTS: Five patients had several episodes of afebrile convulsion at ages older than 12. With the exception of one patient who began to show convulsive episodes at 13, no other XPA patients exhibited febrile seizures. As far as our 33 XPA patients were concerned, 15% exhibited epilepsy, and 3% experienced febrile seizures. CONCLUSIONS: Japanese XPA patients showed a lower incidence of febrile seizures, while exhibiting a higher incidence of epilepsy. It is assumed that the brain of young patients with XPA is difficult to develop convulsions.

Adolescent↗

Ovariectomy is sufficient to accelerate spontaneous skin ageing and to stimulate ultraviolet irradiation-induced photoageing of murine skin.

BACKGROUND: Wrinkling and sagging of the skin during photoageing is physiologically associated with diminished elasticity, which can be attributed to increased fibroblast-derived elastase activity. This degrades the dermal elastic fibres needed to maintain the three-dimensional structure of the skin. We previously reported that ovariectomy accelerates ultraviolet (UV)B-induced wrinkle formation in rat hind limb skin by altering the three-dimensional structure of elastic fibres. OBJECTIVES: In this study, we used hairless mice to assess the effects of ovariectomy with or without chronic UVA or UVB radiation on sagging and wrinkling of skin, on the elasticity of skin, as well as on matrix metalloproteinase activities in the skin. METHODS: Ovariectomies or sham operations were performed on 6-week-old female ICR/HR hairless mice. RESULTS: Even in the ovariectomy group without UV irradiation, the skin elasticity was significantly decreased during the 3-13 weeks after ovariectomy, which was accompanied by a significant increase in elastase activity in the skin. After UVA or UVB irradiation, skin elasticity was significantly decreased to a greater extent in the ovariectomy group than in the sham operation group, and this was accompanied by a reciprocal increase in elastase activity but not in the activities of collagenases I or IV in the skin. Consistent with the decreased skin elasticity, UVA irradiation for 12 weeks elicited more marked sagging in the ovariectomy group than in the sham operation group. UVB irradiation for 12 weeks also induced more marked wrinkle formation in the ovariectomy group than in the sham operation group. CONCLUSIONS: These results suggest that ovariectomy alone is sufficient to accelerate skin ageing and to increase UV sensitivity, which results in the further deterioration of the skin and photoageing, and may account for the accelerated skin ageing seen in postmenopausal women.

Animals↗

Fractionation of normal and leukemic T-cells by lectin-affinity column chromatography.

A method for rapid fractionation of normal and leukemic T-cells (Jurkat, RPMI-8402, MOLT-4), using lectin-affinity column chromatography, is described. CNBr-activated Sepharose 6MB was used as a non-mobile phase. The gel was covalently conjugated with Dolichos biflorus agglutinin (DBA) over 24 h. The normal cells were eluted by phosphate buffered saline (Ca(2+) and Mg(2+) free), while the leukemic T-cells, interacting with DBA, were removed by N-acetyl-D-galactosamine or by low-concentrated acetic acid as a mobile phase. The cell fractions were detected spectrophotometrically at 600 nm. The rate of cell elution decreased in the order: normal>leukemic T-cells. The viability and the type of separated T-cell fractions were characterized by flow cytometry, using adequate fluorescent antibodies. The interactions between leukemic T-cells and DBA-saturated Sepharose beads were examined by fluorescent microscopy, using fluorescent isothiocyanate-DBA as a fluorescent marker.

Antigens, CD↗

Augmentation of monocyte interleukin-8 production by psoralen/UVA-treated CD4+ T cells.

Treatment of cells with psoralen and ultraviolet A light (UVA) modulates their cytokine production. As extracorporeal photochemotherapy has been reported to induce cytokine production by monocytes, we quantified interleukin-8 (IL-8), a representative chemokine produced by monocytes, in culture supernatants from human peripheral blood mononuclear cells (PBMC) treated with 8-methoxypsoralen (8-MOP) and UVA. Lipopolysaccharide stimulated IL-8 production in 8-MOP-phototreated PBMC more efficiently than those untreated or treated with 8-MOP or UVA. More interestingly, when cultured with T-cell-stimulating anti-CD3 and anti-CD28 antibodies, 8-MOP/UVA-treated PBMC produced enhanced amounts of IL-8 with an increased level of IL-8 mRNA expression. Depletion of CD4 but not CD8 T cells from PBMC abrogated this augmented IL-8 elaboration, and CD4 T cells per se secreted no substantial amount of IL-8 even upon CD3/CD28 stimulation. Thus, 8-MOP/UVA-treated CD4 T cells stimulated monocytes to secrete IL-8. The IL-8 overproduction was induced by direct contact of monocytes with 8-MOP/UVA-treated CD4 T cells but not by cytokines from the treated CD4 T cells. These findings imply that in extracorporeal photochemotherapy, monocytes effectively produce IL-8 by cell-to-cell contact with 8-MOP/UVA-treated malignant CD4 T cells. The augmentation of monocyte cytokine/chemokine production by 8-MOP/UVA may be one of the mechanisms underlying the therapeutic efficacy of extracorporeal photochemotherapy.

Adult↗

Woman with UV hypersensitivity and a de novo unbalanced chromosome translocation.

We report a Japanese woman with de novo 6p monosomy and 10q trisomy [46,XX,der(6)t(6;10)(p25.1;q25.2)] whose clinical manifestations resemble those of xeroderma pigmentosum (XP) and Cockayne syndrome (CS), known as premature aging syndromes. She had a history of easy sunburning and presented a number of freckles and hypopigmented spots on her face as those of XP. Magnetic resonance imaging and computed tomography scanning demonstrated intracranial abnormalities like those seen in CS. DNA repair studies using the patient's fibroblasts demonstrated hypersensitive responses to ultraviolet (UV). XP, CS, and UV-sensitive syndromes with photosensitivity disturbances have been known as DNA repair abnormalities. However, an association of 6p monosomy with these diseases has not been reported so far. Molecular analysis of the patient we described may contribute to the identification of novel DNA-repair-related gene(s) and/or to the senile mechanism.

Adult↗

Stable operation of a 300-m laser interferometer with sufficient sensitivity to detect gravitational-wave events within our galaxy.

TAMA300, an interferometric gravitational-wave detector with 300-m baseline length, has been developed and operated with sufficient sensitivity to detect gravitational-wave events within our galaxy and sufficient stability for observations; the interferometer was operated for over 10 hours stably and continuously. With a strain-equivalent noise level of h approximately 5x10(-21)/sqrt[Hz], a signal-to-noise ratio of 30 is expected for gravitational waves generated by a coalescence of 1.4M-1.4M binary neutron stars at 10 kpc distance. We evaluated the stability of the detector sensitivity with a 2-week data-taking run, collecting 160 hours of data to be analyzed in the search for gravitational waves.

Astronomy↗

Analytical method to examine the effects of carbon dioxide lasers on skin: a study using wrinkles induced in hairless mice.

BACKGROUND AND OBJECTIVE: Investigation of the wrinkle smoothing process elicited by CO(2) laser treatment is important for understanding the mechanism involved in their repair. STUDY DESIGN/MATERIALS AND METHODS: Hairless mice with wrinkles induced in their dorsal skin by long-term exposure to ultraviolet radiation in the wavelength range of 290-320 nm were treated with a CO(2) laser. By using this model, we investigated the external appearance, histologic changes, and the mechanical properties of the skin during the wrinkle repair. RESULTS: Laser treatment with an appropriate intensity caused wrinkles to smooth completely. In the healing process, reepithelialization and collagen tissue regeneration in the upper dermis was observed. However, marked changes in the skin were noted, such as increases in the collagen layer and in the skin thickness, and changes in the mechanical properties of the skin, despite the favorable external appearance. CONCLUSIONS: An abnormal state characterized by excessive collagen regeneration and other changes in the dermis occur concomitantly with wrinkle smoothing.

Animals↗

Xeroderma pigmentosum--bridging a gap between clinic and laboratory.

Xeroderma pigmentosum (XP) is an autosomal recessive photosensitive disorder with an extremely high incidence of UV-related skin cancers associated with impaired ability to repair UV-induced DNA damage. There are seven nucleotide excision repair (NER) complementation groups (A through G) and an NER proficient form (XP variant). XPA, B, D and G patients may also develop XP neurological disease. The laboratory diagnosis of XP can be performed by autoradiography. Recently, the isolation and characterization of the genes responsible for XP have made it possible to use molecular biological techniques to diagnose XP patients, for carrier detection and for prenatal diagnosis, especially in Japanese XPA patients. These techniques include polymerase chain reaction (PCR) and plasmid host cell reactivation assays with cloned XP genes. DNA damage is not repaired by the NER system equally throughout the genome. There are two DNA repair pathways: 1) transcription-coupled repair, and 2) global genome repair. Many factors involved in these pathways are related to the pathogenesis of XP and a related photosensitive disease, Cockayne syndrome. Clinical management consists of early diagnosis followed by a rigorous program of sun protection including avoidance of unnecessary UV exposure, wearing UV blocking clothing, and use of sunblocks on the skin. Although there is no cure for XP, the efficacy of oral retinoids for the prevention of new skin cancers, local injection of interferon, and the external use of a prokaryotic DNA repair enzyme have been reported.

Cockayne Syndrome↗

Selective inhibition of skin fibroblast elastase elicits a concentration-dependent prevention of ultraviolet B-induced wrinkle formation.

We previously reported that wrinkle formation in the skin following long-term ultraviolet B irradiation is accompanied by decreases in skin elasticity and the curling of elastic fibers in the dermis. We further showed that wrinkles could be repaired by treatment with retinoic acid and that this was concomitant with the recovery of skin elasticity ascribed to the repair of damaged elastic fibers. Those studies suggested that decreasing the tortuosity of dermal elastic fibers is an important factor involved in inhibiting or repairing wrinkle formation. Therefore, it is of particular interest to determine whether the inhibition of elastase activity in vivo would prevent the damage of dermal elastic fibers and might abolish wrinkle formation associated with the loss of skin elasticity. Because the major elastase in the skin under noninflammatory conditions is skin fibroblast elastase, we used a specific inhibitor of that enzyme to assess its biologic role in wrinkle formation. The hind limb skins of Sprague-Dawley rats were irradiated with ultraviolet B at a suberythemal dose three times a week for 6 wk. During that period, 0.1-10.0 mM N-phenetylphosphonyl-leucyl-tryptophane, an inhibitor of skin fibroblast elastase, was applied topically five times a week. N-phenetylphosphonyl-leucyl-tryptophane application at concentrations of 0.1-1.0 mM abolished wrinkle formation in a concentration-dependent manner, with a peak for inhibition at 1.0 mM. This inhibition was accompanied by a continued low tortuosity of dermal elastic fibers and a maintenance of skin elasticity. Measurement of elastase activity after 6 wk of ultraviolet B irradiation demonstrated that whereas phosphoramidon-sensitive elastase activity was significantly enhanced in the ultraviolet B-exposed skin, there was no significant increase in that activity in the ultraviolet B-exposed, N-phenetylphosphonyl-leucyl-tryptophane-treated skin. These findings suggest that skin fibroblast elastase plays an essential part in the degeneration and/or tortuosity of elastic fibers induced by cumulative ultraviolet B irradiation.

Animals↗

Carbon dioxide laser treatment promotes repair of the three-dimensional network of elastic fibres in rat skin.

BACKGROUND: We have previously reported that ultraviolet (UV) B irradiation induces a loss of linearity in the three-dimensional structure of dermal elastic fibres, which results in the reduction of elastic properties of the skin and leads to wrinkle formation. We further reported that repair of wrinkles by all-trans retinoic acid is accompanied by recovery of the linearity of elastic fibres. Carbon dioxide (CO2) lasers are widely used for treating wrinkles in cosmetic surgery. OBJECTIVES: To perform CO2 laser treatment of wrinkles induced in rat skin by UVB irradiation and to evaluate changes in the three-dimensional structure of dermal elastic fibres during wrinkle repair. METHODS: Wrinkles were induced in the hind limb skin of Sprague-Dawley rats by UVB irradiation (130 mJ cm-2 three times weekly for 6 weeks), followed by CO2 laser treatment (11.3 J cm-2). The surface appearance of the skin was evaluated by replica observation 6 and 10 weeks after CO2 laser treatment followed by measurement of mechanical properties using a Cutometer. Subsequently, perfusion fixation and digestion with formic acid were performed and elastic fibres were observed by scanning electron microscopy (SEM). Image analysis of SEM micrographs was carried out to evaluate the linearity in the three-dimensional structure of elastic fibres. RESULTS: Six weeks after CO2 laser treatment, all parameters of skin mechanical properties in the UVB-irradiated group recovered to levels of the control non-irradiated group, accompanied by repair of wrinkles and a significant increase in linearity of the three-dimensional structure of elastic fibres. CONCLUSIONS: These findings indicate that CO2 laser treatment has a therapeutic potential to repair wrinkles to non-irradiated levels through recovery of the three-dimensional structure of elastic fibres.

Animals↗

Dermal fluid translocation is an important determinant of the diurnal variation in human skin thickness.

BACKGROUND: Ultrasonography has been used as a non-invasive approach to measure skin thickness. To date there have been no studies on diurnal variations in skin thickness. OBJECTIVES: To evaluate diurnal variations in skin thickness and to compare these with corresponding echogenicity and skin elasticity. METHODS: Measurements by ultrasonography B-mode and by Cutometer SEM 575 were carried out in the morning and in the afternoon on 20 men and 20 women (mean age 30 years) on three areas of the face (forehead, corner of the eye and cheek), the forearm and the upper arm, and the flank, thigh and calf. RESULTS: From the morning to the afternoon, the skin thickness in both sexes significantly decreased on three areas of the face, the forearm and the upper arm, but significantly increased on the thigh and calf. In parallel, the echogenicity significantly increased from the morning to the afternoon on the three areas of the face, the forearm and the upper arm, but decreased significantly on the thigh and calf. Measurements of mechanical properties at four sites demonstrated that from the morning to the afternoon, the major parameters of skin elasticity Ue* and Uf* increased significantly in both sexes on two areas of the face and slightly on the forearm, but decreased significantly on the calf. CONCLUSIONS: The diurnal profiles of skin thickness and skin elasticity in the upper half of the body are the reverse of those in the lower half of the body. These findings suggest that shifts of dermal fluid from the face to the leg by gravity during the day cause the diurnal variation in skin thickness.

Adult↗

Inhibitory effect of an extract of Sanguisorba officinalis L. on ultraviolet-B-induced photodamage of rat skin.

We previously reported that chronic Ultraviolet-B (UVB) irradiation causes wrinkle formation, decreases skin elasticity, and damages/curls dermal elastic fibers. Those UVB-induced wrinkles can be improved by treatment with retinoic acid or with a CO2 laser which results in a recovery of skin elasticity and a repair of elastic fiber linearity. We showed further that topical application of N-phenetyl-leucyl-tryptophane, an agent that specifically inhibits fibroblast-derived elastase, immediately after UVB irradiation inhibited UVB-induced wrinkle formation, maintained skin elasticity, and inhibited changes in the three-dimensional structure of dermal elastic fibers in a dose-dependent manner. In this study, the effects of an extract of Sanguisorba officinalis L., which also inhibits fibroblast-derived elastase, was evaluated for possible inhibition of UVB induced wrinkle formation, maintenance of skin elasticity, and prevention of damage to the 3-dimensional structure of dermal elastic fibers. Hind limb skins of 3-week-old Sprague-Dawley rats were irradiated with UVB at a suberythemal dose 3 times a week for 6 weeks. Simultaneously, an extract of Sanguisorba officinalis L. (at 0.2% (v/v) or 1% (v/v)) was topically applied 5 times per week immediately following each UVB irradiation and 1 d later. The extract of Sanguisorba officinalis L. inhibited wrinkle formation, maintained skin elasticity, and inhibited the decrease of dermal elastic fiber linearity in the rat hind limb skin in a dose-dependent manner. We have confirmed that the inhibition of elastase activity in fibroblasts immediately after UVB irradiation using an extract of Sanguisorba officinalis L. prevents chronic photodamage following UVB irradiation.

Administration, Topical↗

Ovariectomy accelerates photoaging of rat skin.

We have previously reported the formation of wrinkles, a decrease in skin elasticity and a loss in the linearity of dermal elastic fibers in rat hind limb skin irradiated with ultraviolet radiation in wavelength ranging 290-320 nm (UVB) at a suberythemal dose for 6 weeks. Estrogens are considered effective in preventing photoaging in postmenopausal females, but the role of estrogen in the skin remains unclear. In this study we have evaluated the influence of short-term chronic UVB irradiation at a suberythemal dose on the skin of ovariectomized rats. An ovariectomy or a sham operation was performed on each 3 week-old female Sprague-Dawley rat. Starting 1 week after the operation the hind limb skin of each rat was irradiated with UVB at a suberythemal dose (130 mJ/cm2) three times a week for 3 or 6 weeks. Decreases in elasticity and wrinkle formation in the skins of ovariectomized animals were induced more quickly than in the skins of sham-operated animals following UVB irradiation. The linearity of elastic fibers in the ovariectomy group decreased significantly compared with the sham-operation group, but erythema in the ovariectomy group was induced more readily than in the sham-operation group following UVB irradiation. These findings suggest that decreases in the estrogen levels after ovariectomy accelerate photoaging in terms of the morphology and physical properties of the skin surface and the three-dimensional structure of elastic fibers.

Animals↗

The role of elastases secreted by fibroblasts in wrinkle formation: implication through selective inhibition of elastase activity.

We have previously demonstrated that decreases in skin elasticity, accompanied by increases in the tortuosity of elastic fibers, are important early events in wrinkle formation. In order to study the role of elastases in the degeneration of elastic fibers during wrinkle formation we examined the effects of an inhibitor of skin fibroblast elastase, N-phenethylphosphonyl-L-leucyl-L-tryptophane (NPLT), on wrinkle formation in hairless mice skin following UV irradiation. Dorsal skins of hairless mice were exposed daily to UV light for 18 weeks at doses of 65-95 mJ/cm2 and treated topically with 100 microL of 1 mM NPLT immediately after each UV irradiation. Wrinkles on dorsal skins were evaluated from week 6 through week 18. The daily exposure of mouse skin to UV light with less than 1 minimal erythemal dose significantly enhanced the activity of elastase in the exposed skin by week 4, and the elevated levels of elastase activity were significantly reduced by the in vitro incubation with NPLT in a dose-dependent manner to a level similar to that in unexposed mice skin, indicating that NPLT can efficiently inhibit the UV-inducible elastase activity. Topical application of NPLT significantly suppressed wrinkle formation when compared with vehicle controls by week 15 of treatment (P < 0.05). Histochemistry of elastic fibers with Orcein staining demonstrated that there were no obvious decreases of the fine elastic fibers in UV-exposed NPLT-treated skin in contrast to their marked decreases in the UV-exposed vehicle-treated skin. These findings suggest that skin fibroblast elastase plays a decisive role in wrinkle formation through the degeneration of elastic fiber.

Animals↗

Epidermal change can alter mechanical properties of hairless mouse skin topically treated with 1alpha, 25-dihydroxyvitamin D(3).

Wrinkle formation caused by photoaging clearly involves changes of extracellular matrix components and mechanical properties of the skin. Recently, it was reported that the topical application of 1alpha, 25-dihydroxyvitamin D(3) to hairless mouse skin induced wrinkling. Here we have evaluated the effect of topical application of 1alpha, 25-dihydroxyvitamin D(3), which causes skin wrinkling, on the mechanical properties of the hairless mouse (HR/ICR) skin, using a commercially available non-invasive in vivo instrument. The elasticity element of the skin was unchanged, but the viscosity element significantly increased. Histologically, the epidermis became remarkably thick, but no conspicuous changes were observed in the dermis. Changes in the mechanical properties of the skin after 1alpha, 25-dihydroxyvitamin D(3) treatment take place through epidermal physical variation, especially changes of viscosity elements. It is suggested that the visco-elastic properties of the epidermis are also attributable to the morphology as well as the mechanical properties of the skin.

Administration, Topical↗

Biological activities of the lectin, abrin-a, against human lymphocytes and cultured leukemic cell lines.

The cytoagglutination by abrin-a against human cultured cell lines derived from acute lymphoblastic leukemia (ALL) and human peripheral blood lymphocytes obtained from normal adults and from patients with adult T cell leukemia (ATL) was investigated. Among acute T lymphoblastic leukemia (T-ALL) cell lines, abrin-a showed strong cytoagglutination against relatively differentiated cell lines, such as Jurkat and CCRF-HSB-2. Among acute B lymphoblastic leukemia (B-ALL) cell lines, abrin-a strongly agglutinated an immature cell line, NALM6. In comparison with ALL cell lines, cytoagglutination by abrin-a against normal lymphocytes was weak. Abrin-a showed higher cytoagglutination against lymphocytes derived from ATL than lymphocytes derived from normal adults. In connection with the cytoagglutination, abrin-a-induced cytotoxicity against human cultured leukemic cell lines was evaluated. In proportion to the extent of cytoagglutination, abrin-a induced cytotoxicity in Jurkat, CCRF-HSB-2, MOLT-4, RPMI8402, and BALL-1 as well. Although CCRF-CEM and BALM-1 were both weakly agglutinated by abrin-a, these cell lines were very sensitive to the abrin-a-induced cytotoxicity. NALM6 was strongly agglutinated by abrin-a, but abrin-a exhibited less strong cytotoxicity against this cell line. These results suggest the feasible application of abrin-a as a tool to distinguish the human leukemic cells and its potential for clinical application.

Abrin↗

Interaction of the hemolytic lectin, CEL-III, with cultured human leukemic cell lines.

We studied interaction of CEL-III with cultured human leukemic cell lines and lymphocytes from normal adults by evaluating the extent of cytotoxicity and cytoagglutination. Among acute T lymphoblastic leukemia (T-ALL) cell lines, CEL-III displayed increased toxicity against different acute lymphoblastic leukemia (ALL) cell lines as a function of increasing differentiation stage. In the case of acute B lymphoblastic leukemia (B-ALL) cell lines, CEL-III showed strong cytotoxicity against relatively immature cell lines. We found that CEL-III was more toxic for ALL cell lines than leukocytes obtained from peripheral blood of healthy adults. Strong influence of the additional amount of calcium ion on the extent of cytotoxicity was observed. In addition, we describe a new way to evaluate the extent of cytoagglutination in "% of agglutinated cells". These findings make CEL-III a promising candidate in research for lectins which bind to and destroy only the targeted leukemic cells.

Adult↗

Age-related alterations of echogenicity in Japanese skin.

BACKGROUND: Ultrasonic methods are commonly used for the noninvasive measurement of skin thickness. The effects of ageing on the skin have been reported to differ between Asians and Caucasians. Therefore, it is possible that the echogenicity of the skin on ultrasonographic images reflects differences in the skin architecture and properties that may vary among races and environments. OBJECTIVE AND METHODS: Since there have been a few reports on ageing-related changes in ultrasonic echogenicity in Caucasian skin, but not in Asian skin, we evaluated age-related changes in the echogenicity of ultrasonographic images by the ultrasonic B mode at 3 sites on the face (forehead, eye corners, cheeks) considered as sun-exposed areas and on the ventral forearms considered as weakly sun-exposed areas in 130 Japanese females aged from 18 to 83 years. The dermis was divided into 3 layers (upper, middle, lower), and echogenicity was evaluated in each area. RESULTS: No age-related change in echogenicity was observed in the entire dermis. When the dermis was divided into 3 layers (upper, middle and lower dermis), the echogenicity was decreased in the upper layer and increased in the lower layer with age in all skin areas tested. In contrast, there were no age-related changes of echogenicity in the middle dermis. CONCLUSION: These findings suggest that, as for Caucasians, echogenicity in the upper and lower dermis is a useful tool for evaluating skin ageing in the Japanese.

Adolescent↗