Biomedical subjects
Publications and source records attributed to H Shibata.
The structures of new antibacterial diterpenoids that had been isolated from Sarcodon scabrosus were established by chemical and spectral means to be sarcodonin L (2) and M (3), both having the cyathane skeleton. Other antibacterial compounds were identified to be allocyathin B2 (1), sarcodonin G (4) and sarcodonin A (5) by comparing their spectral data with those of authentic samples.
Two mutant forms, which had truncated N-terminals, of lipase activator protein (LipB) from Pseudomonas aeruginosa TE3285 were prepared, and their molecular properties and activity were compared with those of the full-length form. A truncated LipB lacking its hydrophobic N-terminal 21 residues was dispersed homogeneously in solution, and could reactivate the stoichiometric amount of denatured lipase. In contrast, full-length LipB formed soluble aggregates, and reactivated less than an equimolar amount of the lipase even under the most suitable conditions. These findings suggest that some or all of the N-terminal 21 residues caused aggregation of the protein molecules, and prevented LipB from fully stoichiometric reactivation. A truncated LipB lacking the N-terminal 61 residues also reactivated denatured lipase, suggesting that the N-terminal 61-residue region of LipB is not involved in reactivation.
Catalase catalyzed the peroxynitrite-mediated nitration of 4-hydroxyphenylacetic acid. The curve for the pH dependence of nitration was similar to that for the reaction between peroxynitrite and phenol. Cyanide, azide, and 3-amino-1,2,4-triazole inhibited the nitration in a dose-dependent way. When catalase was mixed with peroxynitrite, Compound I was detected as an intermediate. Because azide was an electron donor for the peroxidatic action of catalase, and because 3-amino-1,2,4-triazole inhibited catalase activity by binding with Compound I, peroxynitrite-mediated phenolic nitration was probably accompanied by Compound I formation. Both catalase and superoxide dismutase protected Escherichia coli from peroxynitrite toxicity.
Hypophosphatasia (HOPS) is an inherited disorder characterized by defects in skeletal mineralization due to the deficiency of tissue-nonspecific alkaline phosphatase (TNSALP). To date, various mutations in the TNSALP gene have been identified. Especially, a deletion of T at position 1735 (1735T-del) located in exon 12 has been detected in three genetically unrelated Japanese patients, which seems to be one of the hot spots among the causative mutations in Japanese HOPS patients. 1735T-del causes a frame shift downstream from codon 503 (Leu), and consequently the normal termination codon at 508 is eliminated. Since a new inframe termination codon appears at codon 588 in the mutant DNA, the resultant protein is expected to have 80 additional amino acids. Expression of the mutant TNSALP gene using COS-1 cells demonstrated that the protein translated from the mutant 1735T-del had undetectable ALP activity, and its molecule size was larger than normal, as expected. Interestingly, an immunoprecipitation study of patients' sera using antibody against TNSALP revealed an abnormal protein which corresponded in size to the mutated TNSALP expressed by COS-1 cells, suggesting that the abnormal TNSALP is made by HOPS patients. The detection of TNSALP in cells transfected with 1735T-del using an immunofluorescent method exhibited only a faint signal on the cell surface, but an intense intracellular fluorescence after permeabilization.
The aim of this study was to elucidate perimenopausal bone loss in relation to menstrual conditions and to investigate the long-term effect of menopause on bone loss in aged women. The rate of change in bone mineral density (BMD) was measured twice at an exact interval of 12 months by dual-energy X-ray absorptiometry (DXA) at the lumbar spine in 176 pre- and postmenopausal healthy women 41-65 years of age. Serum follicle-stimulating hormone, intact and N-fragment osteocalcin (OC), three types of vitamin D3, parathyroid hormone (PTH), and calcitonin were also determined. Women who exercised regularly or had anatomical changes at the lumbar spine were excluded from this study. The subjects were divided into eight groups based on their menstrual status and years since menopause. Annual bone loss at the lumbar spine of premenopausal women with regular menstruation was -0.2+/-1.9% (95% confidence interval, -0.9 approximately -0.4%) and was not statistically different from zero, while that of women with irregular menstruation or at menopausal transition was -2.1+/-3.4% (-3.4 approximately -0.8%), and -3.3+/-2.3% (-5.2 approximately -0.3%), respectively, and was significantly different from zero. Serum OC levels of women at menopausal transition were significantly higher than those of women with regular menstruation, suggesting that bone loss had commenced in these women. The rate of annual change in BMD of women who were menopausal for 1-3, 4-6, 10-12, and more than 13 years was -3.1+/-4.0% (-4.7 approximately -1.5%), -1.2+/-2.6% (-2.2 approximately -0.2%), -1.0+/-3.0% (-2.3 approximately -0.3%), and -2.3+/-2.1% (-3.7 approximately -1.0%), respectively, and was significantly less than zero. But the annual bone loss of women who were menopausal for 7-9 years was -1.5+/-2.6% (-3.0 approximately -0.1%) and was not statistically significant from zero. These results indicate that postmenopausal women lose BMD in two phases. The early bone loss is rapid and commences during irregular menstruation, then is attenuated within 6 years after the onset of menopause. The second bone loss commences after the attenuation of the first bone loss. Among bone metabolic hormones, intact PTH alone showed an age-related increase and was suggested as being a causal factor of bone loss in women who were menopausal for 13 years or more.
We evaluated the concentration of epidermal growth factor (EGF) in platelets, serum and plasma obtained from 47 patients with Graves' disease, 7 with hypothyroidism and 20 healthy subjects. The platelets of the subjects were collected from platelet rich plasma and lysed by freezing and thawing. Subsequently the platelet debris was treated with Triton X-100. The EGF concentration was determined by homologous radioimmunoassay. The concentration of EGF in the platelets in 14 patients with untreated Graves' disease was significantly higher than that in the healthy controls. After treating these 14 patients with antithyroid agents, the EGF concentration in the platelets decreased to the level of the healthy controls. The EGF concentration in the platelets in the 7 untreated hypothyroid patients decreased after replacement therapy with thyroxine. The mean volume of the platelets in the 14 patients with untreated Graves' disease was significantly larger than in the control and decreased after treatment with antithyroid agents. The serum and plasma levels of EGF in the 7 untreated hypothyroid increased after replacement therapy. In conclusion, thyroid function affected the concentration of EGF in the platelets of patients with thyroid disorders.
To estimate the risk of hepatitis C virus (HCV) infection among blood donors, we conducted a retrospective cohort study with 448,020 HCV-seronegative donors who donated blood more than once between February 1992 and July 1997 in Osaka (a total of 2,676,738 allogeneic blood donations). The donors were divided into four age groups according to the age at the initial donation: Group A (16-24 years), Group B (25-34 years), Group C (35-49 years) and Group D (50-64 years). Fifty-nine donors became infected with HCV among the 448,020 HCV-seronegative donors who donated blood more than once within a period of approximately five years. In a total of 1,095,668 person-years of observation (PYO), the incidence rate was 5.38 per 105 PYO, with the 95% confidence interval (95% C.I.) being 4.10 to 6.95. There was no significant difference in the incidence rate between males and females. Young donors between the ages of 16 and 24 (8.89; 95% C.I., 6.04 to 12.61) had a significantly higher incidence rate of HCV infection than donors between the ages of 35 and 49 (1.81; 0.67 to 3.95). The cumulative risk of HCV infection among donors between the ages of 16 and 64 was estimated to be 0.27% (95% C.I., 0.16 to 0.39) for males and 0.27% (95% C.I., 0.15 to 0.38) for females. Based on the recent age-specific incidence rate, the cumulative risk of HCV infection among blood donors was estimated to be about 0.3% in the Osaka district of Japan. The incidence rate differed among age groups, indicating that HCV infection is associated with age-related behaviors and the need for further epidemiological research towards the eradication of community-acquired HCV infection.
The prevalence rates of affective disorders among the elderly in a rural community according to the criteria of the third edition of Diagnostic and Statistical Manual of Mental Disorders were investigated. The survey used a two-phase method which combined a self-administered depression scale and diagnostic interviews by psychiatrists. The subjects were all 766 persons aged 65 years or older in a rural village in Japan. In the first phase, 698 persons completed a self-administered scale, the Center for Epidemiologic Studies Depression scale (CES-D). In the second phase, 83 persons scoring 12 points or more on the CES-D and an additional 8 persons who, for unknown reason, did not respond to the CES-D were assessed by psychiatrists using a modified version of the Diagnostic Interview Schedule. The subjects' physical health and life events, the presence of dementia, and other factors were taken into account when diagnoses were made. The point prevalence rates of depression without dementia as a comorbid condition by category were as follows: major depression, 0.5%; dysthymic disorder, 0.3%; and atypical depression, 0.4%. The point prevalence rates of depression with dementia as a comorbid condition were as follows: major depression, 0.7%; dysthymic disorder, 0.4%; and atypical depression, 0.4%. Major depression was more prevalent in women than in men and was more prevalent in persons aged 75 years of older than in younger subjects.
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Sera from randomly selected 345 pregnant Nepalese women aged 16-36 years and 13 women with bad obstetric history (BOH) were tested for the presence of Toxoplasma antibodies using microlatex agglutination (MLA) and ELISA methods. The overall prevalence was 55.4% (191/345). Prevalence was slightly higher (59.0%) in older age-group (27-36 years) compared with younger age-group (16-26 years) (52.2%). No significant difference in antibody prevalence in women belonging to two different ethnic-groups (Tibeto-Burmans 57.8%, Indo-Aryans 52.7%) was observed (p>0.05). MLA antibody titer ranged from 1:16 to 1:2,048. Over three-fourth of the women showed either high (1:510 or over) or low (1:16 or 1:32) antibody titer. Three percent (6/191) of MLA antibody positive subjects had Toxoplasma IgM antibodies by IgM-ELISA. All six IgM antibody positive pregnant women had MLA antibody titer of over 1:510. Of the total 13 women with BOH, 5 (38.5%) had Toxoplasma antibodies of which 2 (40.0%) were positive for Toxoplasma-IgM antibodies.
Recently, subsegmental transcatheter hepatic arterial embolization under balloon occlusion of the corresponding hepatic vein has been performed to treat hepatic infarction in subregion hepatocellular carcinoma (HCC). Here, we report subsegmental transcatheter hepatic arterial embolization under balloon occlusion of the corresponding hepatic vein with styrene maleic acid neocarzinostatin lipiodol (SMANCS) (SMANCS-TAE under balloon occlusion of the corresponding hepatic vein). This study included 9 patients with HCC who underwent SMANCS-TAE under balloon occlusion of the corresponding hepatic vein. In all patients, the therapeutic effects (TE) were evaluated according to the criteria of direct response to liver cancer treatment on abdominal computed tomography (CT) 3 weeks after surgery. In 7 patients who could be followed for more than one year, there was no postoperative relapse at the site of treatment. Furthermore, this procedure facilitated the detection of accumulation of SMANCS not only in the tumor but also in the subregion of the tumor in patients with HCC involving immature arterial tumor neoplastic vessels. In patients with large HCC complicated by severe heart failure showing a poor general condition, this procedure allowed treatment to be completed without complication. SMANCS-TAE under balloon occlusion of the corresponding hepatic vein, which can also embolize the portal vein by applying targeting chemotherapy with SMANCS, may cause necrosis not only in the tumor but also in noncancerous liver tissues. This procedure may be an indication for a larger number of cases than standard TAE, facilitating more complete local treatment.
Previous studies on young and middle-aged adults have demonstrated a correlation between certain personal health practices and reduced mortality. However, we have little knowledge to what extent the findings can be generalized to older adults. Our purpose was to investigate the impact of health practices on subsequent changes in the physical and mental well-being of the elderly. We used longitudinal data of a national representative sample of 2,200 older adults aged 60 and over at baseline. This six-year prospective study examined the associations of six items related to personal health habits--cigarette smoking, alcohol consumption, physical exercise, eating breakfast, hours of sleep, and relative weight--with subsequent health status change. Not smoking was the only health practice that achieved a statistically significant relationship with the reduction of future mortality risk. Obesity (20% or more overweight) was a risk factor for the subsequent impairment in activities of daily living. Those who reported a high frequency of exercise and sleeping 7 or 8 hours per night at baseline were less likely to show decreases in their levels of mental well-being. These results suggest that not smoking, weight control, physical exercise, and sleep patterns may have an important role in maintaining physical and mental well-being in older adults.
This study examined (1) the direct effect of the duration of caregiving on caregiver psychological distress, and (2) two- or three-way interactions between duration, stressors (elderly's physical and cognitive impairments), and personal (caregiver's economic or work status) or social (informal or formal supports) resources. We interviewed 833 primary family caregivers of non-institutionalized frail elderly who had been selected through a screening process of all residents aged 65 and over (21,567 persons) in a suburban area of Tokyo. Caregiver psychological distress was evaluated by "Caregiving Burden Scale" as a caregiving-specific psychological measurement, and "Center for Epidemiologic Studies Depression Scale (CES-D)" as a general psychological measurement. The results were as follows. 1. For Caregiving Burden, duration showed a direct effect, as those who had been providing care for a longer duration of time reported higher burden. We found no interactions between duration, stressors, and resources on caregiving burden. 2. For CES-D, duration had interactions, but no direct effect. (1) Two-way interactions were observed between duration and caregiver's economic or work status, as caregivers with a low economic status or who were unemployed showed a stronger negative impact from duration of caregiving. (2) Three-way interactions were observed between duration, the elderly's ADL impairment, and informal support. Informal support, such as a secondary caregiver, buffered the negative impact of the elderly's ADL impairment in cases with a shorter duration of caregiving, but not for those with longer duration. (3) Three-way interactions were observed between duration, the elderly's cognitive impairment, and formal emotional support. Formal emotional support buffered the negative impact of the elderly's cognitive impairment for those with a longer duration of caregiving, but not for those with a shorter duration. These findings suggest that stress-buffering resources differ according to duration of caregiving.
The contrast medium-removing effect of hemofiltration (HF) and hemodiafiltration (HDF) was experimentally investigated using a bovine blood tank model. HF and HDF were performed at a blood flow rate of 100 ml/min with a polysulfone hemofilter (PS filter-CF; membrane area: 0.7 m2). Two hundred milliliters of iomeprol (300 mgI/ml) was administered by a single injection into 4 liters of bovine blood. The blood half-lives of iomeprol were 1.0 hr for the high flow rate HDF group [replacement fluid flow rate (QF): 10 ml/min and dialysate flow rate (QD): 40 ml/min], 1.8 hr for the HDF group (QF: 10 ml/min and QD: 10 ml/min), and 3.8 hr for the HF group (QF: 10 ml/min). The mean clearance rates were 39.7 ml/min for the high flow rate HDF group, 21.4 ml/min for the HDF group, and 12.0 ml/min for the HF group. Iomeprol was mostly excreted in the waste fluid. It is concluded that HDF can remove contrast media more effectively than HF.
The administration of a single, daily 600 mg dose of ursodeoxycholic acid (UDCA) at bedtime and 3-200 mg doses per day at mealtime was conducted for 6 patients with gallstone and choledocholithiasis who were undergoing biliary drainage for the purpose of improving jaundice. Hepatic bile was collected from a drainage tube after a lapse of time in order to compare the bile acid compositions and cholesterol saturation index (SI) in bile for the 2 protocols. A significant increase in UDCA levels in hepatic bile was observed after both UDCA administration at bedtime and mealtime, but the effect of bedtime administration was significantly greater than that of mealtime administration. Whereas levels of cholic acid and chenodeoxycholic acid (CDCA) decreased for the case of bedtime administration, this was not detected for mealtime administration, although no significant differences among the mean interval values were observed. A significant in difference decreased SI was observed during UDCA bedtime administration, but not during mealtime administration, compared to the SI before administration. This suggests a decreased cholesterol excretion into the bile. Based on these findings and from the point of view of compliance, bedtime administration of UDCA appears to be an effective method.
The relationship between nutrient intake and bone mineral density (BMD) in a community of healthy elderly women was investigated. A three-day nutritional survey was carried out. Subjects were divided into two groups using criteria set by the Recommended Dietary Allowances for the Japanese Fifth Revision (1994). Relationship between nutritional intake and BMD was explored. Intake of energy, protein, fats, and vitamins B1 and B2 correlated positively with BMD, as did the intake of eggs, meat, legume and soya products, other vegetables and potatoes, as well as fat and oil. Those with larger average number of food ingested per day had higher average of BMD. In conclusion, the hypothesis: adequate dietary intake protects against BMD loss, agreed with the results. Sufficient nutrient and food intake is associated with BMD increase, and possibly reduced risk of osteoporosis.
We have investigated the subcellular distribution of GLUT4 by immunofluorescence microscopy after transfection with wild-type or mutant dynamin cDNA into Chinese hamster ovary cells expressing insulin receptor and GLUT4. In the basal state, GLUT4 was distributed exclusively within the cells in the cells overexpressing wild-type dynamin (CHOIR-GLUT4-WT) but was located at the cell surface in the cells overexpressing mutant dynamin (CHOIR-GLUT4-K44E). Insulin induced subcellular shift of GLUT4 to the cell surface in CHOIR-GLUT4-WT cells but had little effect in CHOIR-GLUT4-K44E cells. When insulin-stimulated cells were treated with wortmannin, GLUT4 was redistributed within the cells in CHOIR-GLUT4-WT cell, whereas it remained at the cell surface in CHOIR-GLUT4-K44E cell. These results suggest that dynamin is a regulatory GTPase in endocytosis of GLUT4.
To elucidate the regulation of follistatin production in the liver, we studied changes in steady-state follistatin mRNA levels in cultured rat hepatocytes. Activin A stimulated follistatin mRNA levels in a time- and concentration-dependent manner. The stimulatory effect of activin A on follistatin mRNA was significant at 2 h, maximal at 6 h and declined thereafter. Incubating the cells with EGF increased follistatin mRNA levels at 48 h and later. The EGF-induced increase in follistatin mRNA was markedly inhibited by exogenous follistatin in the culture medium, which blocks the action of activin A synthesized in hepatocytes, suggesting that endogenous activin A at least partly mediated the effect of EGF. We also examined the effects of transforming growth factor-beta (TGF-beta), glucagon and alpha-adrenergic agonist, phenylephrine, on follistatin mRNA levels. TGF-beta increased the follistatin mRNA to levels similar to those caused by activin A. Phenylephrine and glucagon also increased follistatin mRNA levels but the effects were transient and weaker than those caused by activin A. Finally, follistatin mRNA levels were markedly increased in remnant liver 3 h after 70% hepatectomy. The mRNA remained elevated for up to 72 h. These results indicate that the expression of mRNA for follistatin is positively controlled by activin A, TGF-beta and other hormones or neurotransmitters. The stimulatory effect of EGF on follistatin mRNA is mediated by activin A released from hepatocytes.