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Biomedical subjects

Y Higaki

Publications and source records attributed to Y Higaki.

At least 55 records · Page 3Linked to original sources
PubMed1996

Abnormal expression of sphingomyelin acylase in atopic dermatitis: an etiologic factor for ceramide deficiency?

Previously, we demonstrated that there is a marked reduction in the amount of ceramide in the stratum corneum of both lesional and nonlesional forearms in atopic dermatitis (AD), suggesting that an insufficiency of ceramides in the stratum corneum is an etiologic factor in atopic dry and barrier-disrupted skin. In this study, we investigated, as a possible mechanism involved in the ceramide deficiency, whether sphingomyelin (SM) metabolism is altered in AD as compared to normal controls. In stripped stratum corneum and biopsied whole epidermis of patients with AD, SM hydrolysis as measured at pH 4.7 using [choline-methyl-14C]sphingomyelin as a substrate were markedly increased by 27- and 7-fold, respectively. Radio-thin-layer chromatography of the reaction products revealed that, whereas the SM hydrolysis in age-matched normal controls were associated with sphingomyelinase (SMase) that degrades SM to yield ceramides and phosphorylcholine (PC), most of the SM hydrolysis detected in AD were attributable not to the SMase but to a hitherto undiscovered epidermal enzyme, SM acylase, which releases free fatty acid and sphingosyl-PC (Sph-PC) instead of ceramides. The potential of this acylase-like enzyme to generate Sph-PC through SM hydrolysis was corroborated by thin-layer chromatographic analysis of the reaction products obtained using porcine kidney acylase, followed by high-performance liquid chromatography-mass spectrometry. Furthermore, Sph-PC was also detected by high-performance liquid chromatography-mass spectrometry after incubation of SM with atopic stratum corneum samples. On the other hand, the stratum corneum of patients with contact dermatitis or chronic eczema exhibited neither increased SM hydrolysis nor the generation of Sph-PC upon radio-thin-layer chromatographic analysis. These findings suggest that SM metabolism is altered in AD, resulting in a decrease in levels of ceramides, which could be an etiologic factor in the continuous generation of atopic dry and barrier disrupted skin observed in AD.

Amidohydrolases↗
PubMed1996

Effects of a single bout of exercise on glucose effectiveness.

The effects of a single bout of exercise on glucose effectiveness (SG) and insulin sensitivity (SI) in 22 sedentary subjects were estimated with a minimal model approach. The intravenous glucose tolerance test (IVGTT) was performed 1) 11 h after an exercise bout on a cycle ergometer at the lactate threshold level (mild exercise) for 60 min, 2) 11 h after an exercise bout at the 4 mM lactate level (hard exercise) for 36 +/- 1 min, 3) 11 h after an exhaustive-exercise bout (exhaustive exercise) for 96 +/- 7 min, or 4) without any prior exercise (control). Only the exhaustive exercise increased the glucose disappearance constant (2.69 +/- 0.28 vs. 2.05 +/- 0.13%/min; P < 0.05) and SI (15.0 +/- 2.0 vs. 10.3 +/- 0.9 x 10(-5) min/pM: P < 0.05) in comparison with the control condition. The SG and SG at zero insulin (GEZI) were not affected by any exercise condition. However, a marked individual difference in GEZI emerged after the exhaustive exercise and could be divided into two subgroups: one decreased in GEZI (0.014 +/- 0.001 vs. 0.007 +/- 0.001 min-1) and the other increased in GEZI (0.014 +/- 0.001 vs. 0.021 +/- 0.003 min-1). The former subgroup was accompanied by elevated levels of plasma creatine kinase (100 +/- 16 vs. 598 +/- 315 IU/l; P < 0.05) and myoglobin (Mb; 46 +/- 4 vs. 126 +/- 47 ng/ml; P < 0.05), whereas the latter subgroup showed no significant change in creatinine kinase (99 +/- 10 vs. 128 +/- 9 IU/l; P > 0.05) and Mb (50 +/- 7 vs. 51 +/- 4 ng/ml; P > 0.05). In both subgroups, SI was similarly increased after the exhaustive exercise. These results thus suggest that a single bout of exercise that results in muscle damage or changes in muscle permeability, as reflected in the increased creatine kinase and Mb levels, decreases GEZI, whereas exhaustive exercise without such alterations increases GEZI.

Adult↗
PubMed1996

The relationships of testosterone, estradiol, dehydroepiandrosterone-sulfate and sex hormone-binding globulin to lipid and glucose metabolism in healthy men.

We investigated the relationships of plasma sex hormones (free testosterone; free T, estradiol; E2 dehydroepiandrosterone-sulfate; DHEA-S) and sex hormone-binding globulin (SHBG) levels to lipid and glucose metabolism cross-sectionally in 212 apparently healthy men aged from 18 to 59 years. A multiple linear regression analysis for lipid and glucose parameters with age, body mass index (BMI), percent body fat (%fat), waist to hip ratio (WHR), estimated maximal oxygen uptake (VO2max), alcohol and cigarette consumption, sex hormones, and SHBG, respectively, as independent variables, was performed. DHEA-S was indicated as one of the independent predictors of both high density lipoprotein cholesterol (HDL-C), with a positive relation, and of triglyceride and total cholesterol/HDL-C ratio, with a negative relation, while SHBG was one of the predictors of both HDL-C, with a positive relation, and of fasting insulin, with a negative relation. The E2 level was found to be negatively related to both low density lipoprotein cholesterol and fasting blood glucose. These findings thus suggest that the higher levels of SHBG, DHEA-S and E2 within physiological ranges in healthy men may partially help to maintain a desirable profile of the plasma lipid and glucose metabolism.

Adolescent↗
PubMed1995

Milium-like syringoma in the perianal region.

We report a case of syringoma clinically presenting as milia in the perianal region. Milium-like syringoma is an unusual clinical variant of the tumor, and this is, to our knowledge, the first reported case occurring perianally.

Adult↗
PubMed1995

[Serum ECP level of infants of atopic dermatitis].

Forty-seven infants with atopic dermatitis (AD) were examined for ECP (eosinophil cationic protein) levels in sera at 3 to 4, 6 to 7, 12 and 18 months after birth. ECP levels in AD were significantly higher than those of control infants at every examination. The levels of ECP in AD were significantly correlated with the severity of dermatitis judged by a slightly modified version of the method of Businco et al. We concluded that ECP levels in sera are a useful marker for the severity of dermatitis in infants with AD.

Biomarkers↗
PubMed1995

[Effect of PCBs on insulin sensitivity in rats].

Insulin sensitivity was assessed by euglycemic insulin clamp method in the rats given Kanechlor (KC)-400 for 1 to 12 weeks. As a result, insulin sensitivity was depressed increasingly with period of administration of KC-400. Increases in total cholesterol, HDL-C, triglyceride, lipid peroxide and T3 in blood plasma were also observed in the experimental rats. Voluntary daily activity of rats given KC-400, especially in a later half of night-time, had been depressed since approximately 9 weeks after start of the experiment. It was concluded that depression of insulin sensitivity might be related to not only disturbance of glucose and lipid metabolism, but reduced daily activity in conjunction with disturbed thyroid function.

Animals↗
PubMed1994

Mechanisms involved in the inhibition of growth of a human B lymphoma cell line, B104, by anti-MHC class II antibodies.

The mechanisms involved in the inhibition of growth of a human B lymphoma cell line, B104, by anti-MHC class II antibodies (Ab) were compared with those in anti-IgM Ab-induced B104 growth inhibition. Two anti-MHC class II Ab, L227 and 2.06, inhibited the growth of B104 cells, although 2.06, but not L227, needed to be further cross-linked with a goat anti-mouse IgG Ab (GAM) to show the effect. L227 induced an increase in intracellular free Ca2+ concentration ([Ca2+]i) from the intracellular pool and little or no protein tyrosine phosphorylation, phosphatidyl inositol turnover, or expression of Egr-1 mRNA, whereas 2.06 plus GAM induced an increase in [Ca2+]i from both the intracellular and, in particular, the extracellular pools. The inhibition of B104 cell growth induced by anti-MHC class II Ab was Ca(2+)-independent and not inhibited by actinomycin D or cyclosporin A, and cell cycle arrest at the G2/M interphase was not observed. These features are very different from those observed in B104 cell death induced by anti-IgM Ab. Neither DNA fragmentation nor the morphology of apoptosis was observed. These findings demonstrate that cross-linking of MHC class II molecules transduced the negative signals through intracellular mechanisms different from those present in the cross-linking of surface IgM.

Antibodies, Monoclonal↗
PubMed1994

Regional analysis of ceramides within the stratum corneum in relation to seasonal changes.

We studied the regional variations and seasonal changes of ceramide quantities in the stratum corneum of human skin. In summer, the total lipid amounts extracted from the stripped stratum corneum were highest in the forehead, followed by the chest and upper back, with the lowest level in the sole of the foot. In winter, while the total lipid distribution followed the same trend as that in summer, the absolute amounts slightly decreased, especially in the forehead and chest, as compared with those found in summer. Ceramide analysis showed that while a higher level was seen in the cubital fossa in summer, the level was highest in the forehead during winter. A seasonal comparison of ceramide mass revealed a slightly increased level in winter compared with summer, at almost all sites tested, except in the cubital fossa and dorsum pedis, reflecting seemingly enhanced keratinization in winter. These findings indicate that in young adults, the mass of ceramide remains steady at similar levels at various skin sites, providing maintenance of a pertinent water reservoir and the barrier function of the stratum corneum, even under different seasonal conditions.

Adult↗
PubMed1994

Analysis of beta-glucocerebrosidase and ceramidase activities in atopic and aged dry skin.

To elucidate the mechanisms that are involved in the decrease of ceramide levels in atopic dry skin and in aged skin, we examined both the activities of beta-glucocerebrosidase, which is a major enzyme in ceramide production, and of ceramidase, which is an essential enzyme in ceramide degradation, in the stratum corneum of atopic dry skin and aged skin. The specimens of the stratum corneum of forearm skin were obtained by tape-stripping from 61 healthy volunteers and 23 patients with atopic uninvolved skin. The beta-glucocerebrosidase activity in the stratum corneum extracts was estimated using fluorescent 4-methylumbelliferyl-beta-D-glucopyranoside as the substrate. Ceramidase activity was determined using 14C-palmitoylsphingosine as the substrate. Among the atopic skin samples, neither beta-glucocerebrosidase nor ceramidase activities were different from those of age-matched healthy controls. Nor was the beta-glucocerebrosidase activity deficient in the aged skin samples as compared to that seen in samples from the young, healthy group. In contrast, there was an age-related upregulation in ceramidase activity. The results indicate that the decrease of ceramides in atopic dry skin may not be accompanied by reduced synthesis or by enhanced degradation, each of which is primarily attributable to the above two enzymes, respectively. The pathogenesis of aged dry skin can be explained, at least partially, in terms of elevated ceramidase activity, which results in a disturbance of the lamellar structure of the stratum corneum lipids.

Adolescent↗
PubMed1993

Cyclosporin A and FK506 block the negative signaling mediated by surface IgM cross-linking in normal human mature B cells.

Cross-linking of surface IgM (sIgM) or sIgD by anti-IgM Ab or anti-IgD Ab, respectively, induced DNA synthesis in peripheral blood B cells (PBL-B). Cell division, determined by the increase in the number of M phase cells, was also induced when PBL-B were stimulated with anti-IgD Ab plus IL-4 or Staphylococcus aureus Cowan I (SAC), but far less by stimulation with anti-IgM Ab plus IL-4. Anti-IgM Ab did not suppress the DNA synthesis induced by SAC or anti-IgD Ab plus IL-4, but it did suppress the cell division induced by them. Thus, sIgM cross-linking generates both positive and negative signaling to B-cell proliferation. Cyclosporin A (CSA) and FK506 suppressed DNA synthesis and cell division at relatively high concentrations. On the other hand, CSA and FK506 at lower concentrations blocked the anti-IgM Ab-generated inhibition of cell division without affecting DNA synthesis. Low concentrations of CSA did not affect the cell division induced by anti-IgD Ab plus IL-4 but did increase the cell division induced by SAC or anti-IgM Ab plus IL-4, suggesting that stimulation with SAC, as well as with anti-IgM Ab plus IL-4, generates both positive and negative signals to cell division, whereas sIgD lacks the ability to transduce negative signaling.

Antibodies, Anti-Idiotypic↗
PubMed1993

Rheumatoid papules: a report on four patients with histopathologic analysis.

BACKGROUND: The rheumatoid papule is a recently described skin manifestation of rheumatoid arthritis. OBJECTIVE: Rheumatoid papules from four patients with classic rheumatoid arthritis were examined to determine the origin of this palisading granulomatous reaction. METHODS: Immunofluorescence and electron microscopic studies were performed on biopsy specimens of rheumatoid papules. RESULTS: Leukocytoclastic vasculitis with collagen alteration and lymphohistiocytic infiltration were observed. The immunofluorescence study revealed deposits of immunoglobulins and complement in the vessel walls and in the area of collagen alteration. Electron microscopy revealed epithelioid cell-like histiocytes among altered collagen fibers. These cells contained abundant lysosomes and were connected to neighboring cells by well-developed intricate processes. CONCLUSION: Vasculitis is important in the pathogenesis of rheumatoid papules. In patients with rheumatoid papules, systemic evaluation should be performed because these are a manifestation of rheumatoid vasculitis.

Adult↗
PubMed1993

Blister formation over a soft fibroma of the nipple.

We report a case of soft fibroma on the nipple which was accompanied by a blister. Histologically, a subepidermal blister overlying the tumor and the degeneration of the lower part of the epidermis were observed. The causes of blister formation are briefly discussed.

Adult↗
PubMed1993

Quantitative analysis of stratum corneum lipids in xerosis and asteatotic eczema.

Sphingolipids, a major constituent of intercellular lipids, are an important determinant for both water-holding and permeability barrier function in the stratum corneum. To assess the pathogenic role of sphingolipids in the stratum corneum of dry skin disorders such as xerosis and asteatotic eczema in leg skin, ceramides were quantified by thin layer chromatography after n-hexane/ethanol extraction of resin-stripped stratum corneum and evaluated as micrograms/mg stratum corneum. In healthy leg skin (n = 49), there was age-related decline in the total ceramide, whereas xerosis (n = 25) and asteatotic eczema (n = 16) suffering significantly reduced water-holding properties, exhibited no definite decrease, rather slight increase in ceramide quantity with the same composition of each individual ceramide as compared to healthy age-matched controls. These data indicate that the seemingly elevated level of ceramide is an artificial effect due to inflammatory processes which result from susceptibility to dryness. Analysis of sebum-derived lipids present in the stratum corneum revealed that there was a significant decline in free fatty acids in xerosis and asteatotic eczema as compared to age-matched healthy controls, and a similar decline in triglycerides in the above three groups when compared to younger controls. Although the observed decrease in the stratum corneum lipids may well explain the high incidence of winter dry skin in older people, the progression toward asteatotic eczema can not be accompanied solely by a decrease in ceramide quantity, suggesting that the evolution of xerotic skin is associated with other moisturizing factors and/or environmental stimuli.

Adult↗
PubMed1993

Intravenous glucose tolerance test-derived glucose effectiveness in physically trained humans.

Glucose effectiveness (SG) and insulin sensitivity of sedentary and physically trained males were estimated by the minimal model approach. Trained subjects, who ran 86 +/- 10 km/wk and had 37% higher maximal oxygen consumption than that of sedentary subjects (56.2 +/- 1.2 vs. 40.9 +/- 1.4 ml.kg-1 x min-1, P < 0.01), were studied 16 h and 1 wk after their last training session. After overnight fasting, glucose was administered intravenously (300 mg/kg body wt) within 2 min, and insulin was infused (approximately 13-20 mU/kg given over 5 min) from 20 to 25 min after administration of glucose. Glucose disappearance constant values as an estimate of glucose tolerance were significantly higher in trained subjects after 16 h and 1 wk of their training session (3.29 +/- 0.48 and 3.60 +/- 0.64%/min) than in sedentary subjects (1.92 +/- 0.30%/min, P < 0.05). Insulin sensitivity in trained subjects measured after 16 h and 1 wk of their last training session (26.2 +/- 4.4 and 24.3 +/- 6.0 x 10(-5) min-1 x pM-1) was also higher than that of sedentary subjects (10.3 +/- 1.2 x 10(-5) min-1 x pM-1, P < 0.05). SG, the ability of glucose itself to increase peripheral glucose uptake and suppress hepatic glucose output, was significantly higher in trained subjects after 16 h and 1 wk of their last training session (0.028 +/- 0.003 and 0.030 +/- 0.004/min) than in sedentary subjects (0.017 +/- 0.002/min, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Anti-IgM antibody-induced cell death in a human B lymphoma cell line, B104, represents a novel programmed cell death.

We investigated the mechanisms of anti-IgM antibody-induced cell death in a recently established human surface IgM+ IgD+ B lymphoma cell line, B104, the growth of which is irreversibly inhibited by anti-IgM antibody but not by anti-IgD antibody, and compared it with the cell death of T cells via TCR/CD3 complex and with the cell death of a murine anti-IgM antibody-sensitive B lymphoma cell line, WEHI-231. The rapid time course of B104 cell death and its requirements for de novo macromolecular synthesis and Ca2+ influx suggest that anti-IgM antibody-induced B104 cell death is an active Ca(2+)-dependent programmed cell death. Moreover, cyclosporin A rescued B104 cells from this lethal signal, via surface IgM, suggesting that the intracellular mechanisms involved are quite similar to those of T cell death. DNA fragmentation, which has been reported in TCR/CD3 complex-mediated T cell death, apoptosis, was not involved in the B104 cell death process, but the possible involvement of DNA single-strand breaks was suggested. Observations under light microscopy and transmission electron microscopy indicated that the morphologic features of dying B104 cells resembled necrosis rather than apoptosis. B104 cell death was shown to be quite distinct from that of WEHI-231 in cell death kinetics, the mode of cell death, and the response to cyclosporin A. These data collectively indicate that the death of B104 cells resulting from surface IgM cross-linking represents a hitherto undefined mode of programmed cell death.

Antibodies, Anti-Idiotypic↗