Pesticides and their oxidation products in water and fish from rivers flowing into Lake Biwa.
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Biomedical subjects
Publications and source records attributed to T Tsuda.
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Clathrin-coated vesicles are involved in three receptor-mediated intracellular transport pathways: export from the Golgi apparatus, transfer of lysosomal enzymes from the Golgi apparatus to lysosomes, and endocytosis at the plasma membrane. Seeking evidence of transport abnormalities in distal myopathy with rimmed vacuoles (DMRV), we performed immunohistochemistry for clathrin in muscle biopsy specimens from patients with this disorder or other neuromuscular disorders, and also in control muscle samples resected in orthopedic procedures. While most myofibers from control muscle did not stain for clathrin, some fibers revealed finely granular sarcoplasmic staining. In specimens from patients with Duchenne and Becker muscular dystrophy, amyotrophic lateral sclerosis, peripheral neuropathy, and DMRV, numerous clathrin-positive granules were often scattered through the sarcoplasm and seen to a lesser extent in subsarcolemmal regions. Quantitative immunohistochemical assessment showed more reactivity for clathrin in DMRV than in controls and other diseased muscles, particularly in atrophic fibers and type 2 fibers. Not all strongly clathrin-positive muscle fibers contained rimmed vacuoles, although most fibers with vacuoles were clathrin positive. The result suggests that the lysosome system is activated and receptor-mediated intracellular transport pathways function appropriately in the muscles of DMRV patients.
The effect of dietary cyanidin 3-O-beta-D-glucoside (C3G), a typical anthocyanin pigment, on the generation of thiobarbituric acid reactive substances (TBARS) during serum formation ex vivo and susceptibility of serum to further lipid peroxidation was studied in rats. Rats were fed a diet containing C3G (2 g/kg) for 14 d. Feeding C3G resulted in a significant decrease in generation of TBARS during serum formation. The serum from the C3G-fed group showed a significantly lower susceptibility to further lipid peroxidation provoked by 2,2'-azobis(2-amidinopropane)hydrochloride or Cu2+ than that of the control group. No significant differences were observed in serum phospholipid, triglyceride, esterified cholesterol, and free fatty acid concentrations between the control and the C3G-fed groups. Concentrations of endogenous antioxidants remaining in the serum after blood coagulation were not affected by the C3G feeding. These results demonstrate that feeding C3G increases the ex vivo oxidation resistance of the serum without affecting serum endogenous antioxidant levels, and reduces the TBARS generated during serum formation without changing the concentrations of serum lipids.
BACKGROUND: This study examined the effects of the depletion of leukocytes and platelets from circulated blood on cardiac function after cardiopulmonary bypass in 37 patients who underwent coronary artery bypass grafting or aortic valve replacement. METHODS: Leukocytes and platelets were removed continuously using a blood cell separator, beginning immediately after the start of the operation and ending 1 hour after the release of the aortic cross-clamp in 19 patients (LPD group), but not in the remaining 18 patients (control group). Blood cell counts and levels of thromboxane B2, 6-keto-prostaglandin F1alpha, leukocyte elastase, complements C3a and C4a, thrombin-antithrombin III complex, and D-dimer were determined periodically during and after the operation. The cardiac index, the difference between the central and peripheral core temperatures, and the doses of catecholamines and vasodilators required to support the circulation in the early postoperative period also were assessed. RESULTS: Leukocyte and platelet counts and levels of leukocyte elastase, thromboxane B2, thromboxane2/6-ketoprostaglandin F1alpha, thrombin-antithrombin III complex, and D-dimer were significantly lower in the LPD group than in the control group before and after the release of the aortic cross-clamp and during the perioperative period. There were no significant differences in the levels of 6-keto-prostaglandin F1alpha or complements C3a and C4a between the two groups. The catecholamine dose was significantly lower in the LPD group than in the control group (1.1 +/- 2.5 versus 5.0 +/- 5.2 mg/kg, respectively). Fewer patients required the use of nitroprusside as a vasodilator in the LPD group than in the control group (1/19 versus 12/18, respectively). CONCLUSIONS: The depletion of leukocytes and platelets using a blood cell separator prevents the deterioration of cardiac function after cardiac operations using cardiopulmonary bypass.
Previous study has shown that prebeta1-HDL levels increase in hypercholesterolemia, or high cholesteryl ester transfer protein (CETP) activity. To determine how prebeta1-HDL levels change after treatment with probucol or by following a low-cholesterol diet, we randomly assigned 24 hypercholesterolemic patients to either the probucol (P), or low-cholesterol diet group (D), and measured prebeta1-HDL levels before and after treatments using native two-dimensional gel electrophoresis. We also examined 12 subjects with normolipidemia (N). At baseline, prebeta1-HDL levels were higher in P (P < 0.05) and D (P < 0.05) than in N (9.2 +/- 4.3, 10.4 +/- 5.5, and 5.9 +/- 2.3 mg/dl apo A-I). After a 4-week treatment, prebeta1-HDL levels were still high in P (10.5 +/- 4.2 mg/dl apo A-I, N.S.), but reduced in D (7.7 +/- 3.0 mg/dl apo A-I, P < 0.001). Delta prebeta1-HDL (Y) was positively correlated with deltaCETP mass (X) in P (y = 7.83x - 1.93; r = 0.584, P < 0.05). In summary, high prebeta1-HDL levels in hypercholesterolemia are maintained by probucol but reduced by a low-cholesterol diet. These findings suggest that prebeta1-HDL levels may be regulated by cholesterol and CETP levels.
OBJECTIVE: We determined whether the duration of permissible circulatory arrest could be prolonged by deep hypothermic intermittent circulatory arrest. METHODS: Twenty-five beagles were cooled on bypass to 18 degrees C to initiate deep hypothermia that was maintained for 3 hours. Five protocols were then studied: group 1, uninterrupted bypass during hypothermia; group 2, arrest for 40 minutes during hypothermia; group 3, arrest for 60 minutes during hypothermia; group 4, arrest for 80 minutes during hypothermia; and group 5, intermittent circulatory arrest, consisting of six cycles of 20 minutes of arrest followed by 10 minutes of systemic recirculation during hypothermia (total, 120 minutes of arrest). The oxyhemoglobin concentration in the brain was measured with near infrared spectrophotometry. RESULTS: In groups 2, 3, and 4, the oxyhemoglobin concentration in the brain decreased continuously after arrest, finally reaching a plateau after 24.9 +/- 1.2 minutes. This finding suggested that the available cerebral oxyhemoglobin was depleted. In contrast, the available cerebral oxyhemoglobin was not depleted during hypothermic intermittent arrest in group 5. The mitochondrial respiratory control index was significantly lower in group 4 than in the other groups (p < 0.05). However, there were no significant differences in the respiratory control index for groups 1, 2, 3, and 5. Moreover, the formation of brain edema was significantly lower in group 5 than in the other groups (p < 0.05). CONCLUSIONS: These results indicate that deep hypothermic intermittent arrest can increase the duration of total permissible circulatory arrest and will be a useful modality when prolonged arrest is anticipated.
Although Japanese physicians historically have not disclosed cancer diagnoses to patients, pressures upon physicians to disclose have increased in recent years. We questioned physicians practicing at a private medical hospital in rural Japan about their current approach to cancer disclosure. We compared their responses with responses of physicians in a 1991 study conducted in Japan, and two studies conducted in the United States, in 1961 and in 1977. Seventy-seven clinically active physicians with experience treating cancer patients responded (73% response rate). Forty percent of respondents reported usually telling patients of a cancer diagnosis, over three times more than the 13% who reported such a policy in Japan in 1991. Physicians were significantly more likely (P < 0.001) to make exceptions than physicians in the previous Japanese study, and physicians in the previous U.S. studies. Respondents reported considering more factors in deciding whether to tell than participants in the 1977 U.S. study. Factors predicting an increased probability of disclosure included age (in a hyperbolic relationship), improved prognosis, breast or cervical cancer, and social status and religion (by a minority of respondents). Increase in a substitute decision maker's age was predictive for physicians not to involve the person in decision-making. Most respondents reported their disclosure policy is based on clinical experience. More respondents indicated a likelihood of changing in the future than respondents in the previous U.S. studies. These data suggest Japanese physicians are moving away from a rigid policy of nondisclosure to a policy of selective disclosure, but they have not adopted universal cancer disclosure as practiced in many Western countries. Since young age and advanced age predicted self-reports of not disclosing cancer diagnoses, these data raise the question of whether nondisclosure by age groups represents age discrimination or compassionate medical care tailored to individual patient needs.
Health care for the elderly in Japan is financed through a pool to which all insurers contribute. We analyzed insurers' financial data to evaluate this redistribution system. Cost sharing affected financial performance substantially. The current formula for cost-sharing redistributes elderly health care costs unequally and should be changed.
We review various methods developed for human perspiration measurement and their physiological applications, with special reference to the performance and application of a new home-made ratemeter and instrumentation with a microscope. Many kinds of humidity sensor based on humidity-sensitive electrical properties have been investigated and placed on the market. Recently a capacitive thin-film humidity sensor was constructed and confirmed to be one of the best humidity sensors for accurately and quickly detecting changes in the relative humidity of gas-flow perfused through a ventilated chamber for human perspiration measurement. In this paper we also introduce a new home-made ratemeter with a capacitive humidity sensor, the electrical output of which is not disturbed by changes in ambient temperature, and new instrumentation for directly observing drops of sweat secreted from eccrine glands in human skin and simultaneously measuring the change in amount of perspiration at the same area of skin. Finally, we review physiological applications of the methods for measuring human palmar perspiration including emotional sweating.
The modification of Na+,K+-ATPase with increasing pyridoxal 5'-diphospho-5'-adenosine (AP2PL) concentrations resulted in saturation of the approximately 0.5 mol AP2PL probe incorporation into the Lys-480/mol catalytic alpha-chain and reduced the Na+,K+-ATPase activity to around half without affecting the phosphorylation by acetyl phosphate (AcP), and led to increases in the AP2PL fluorescence caused by ATP and AcP. Further modification with fluorescein 5'-isothiocyanate (FITC) resulted in approximately 0.9 mol FITC probe incorporation into the Lys-501/mol alpha-chain and reduced the activity to below 5% without affecting the phosphorylation by AcP and these fluorescence increases. The ATP binding capacity of the AP2PL-FITC enzyme was shown to be at least 50% of that of the control enzyme (approximately 0.8 mol/mol alpha-chain). This is the first direct demonstration that Na+-bound FITC-modified enzymes accept ATP with an affinity for ATP (K(1/2) > 150 microM) reduced by two orders of magnitude. The data also suggest half site reactivity of Lys-480 as to AP2PL and all site reactivity of Lys-501 as to FITC in the catalytic subunits.
The aim of this study was to develop a simplified method for quantitative analysis of liver scintigraphy with 99Tc(m)-diethylenetriamine pentaacetic acid-galactosyl-human serum albumin (GSA) using spectral analysis. Dynamic liver scintigraphy using GSA was performed in three normal volunteers and 19 patients with chronic liver disease. Dynamic data were obtained with a gamma camera for 30 min after the injection of approximately 185 MBq GSA. The rate constant for the liver uptake of GSA from the blood (Ku, min(-1)), total excretion rate (Ke, min(-1)) and non-specific volume of distribution (Vh) were obtained by spectral analysis. Vh was defined as the volume in the liver region of interest (ROI) occupied by GSA which was in equilibrium with that in the blood. It should be noted that Vh had no units, since the counts in both the liver and heart ROIs were normalized by scan length to obtain counts pixel(-1) min(-). For comparison, compartmental analysis was also performed. A receptor index (LHL15) was calculated by dividing the radioactivity of the liver ROI by that of the liver plus heart ROIs 15 min post-injection. The Ku values obtained by spectral analysis (y) agreed well with those obtained by compartmental analysis (x) (y = 0.953x - 0.013, r = 0.992, S.E.E. = 0.016 min(-1)). The Ke and Vh values obtained by spectral analysis (y) correlated significantly with those obtained by compartmental analysis (x) (y = 1.149x - 0.016, r = 0.826, S.E.E. = 0.017 min(-1) for Ke; y = 1.191x + 0.044, r = 0.975, S.E.E. = 0.021 for Vh). The Ku values obtained by spectral analysis decreased as the severity of liver disease progressed, and were non-linearly related to the LHL15 values, suggesting that Ku is more sensitive to liver damage than LHL15, especially in the early stages of liver damage. These results suggest that spectral analysis applied to dynamic liver scintigraphy with GSA provides a simple, non-invasive and useful tool for the quantitative evaluation of liver function.
OBJECTIVES: We report the results of clinical and genetic studies from 2 related Japanese kindreds with spinocerebellar ataxia type 2 (SCA2). MATERIAL AND METHODS: Family A showed 19 patients through 4 generations, while family B showed 6 patients, including dizygotic twin brothers, through 3 generations. We performed clinical, radiological, neurophysiological, and genetic analyses in the family members. RESULTS: Neurologic analysis of 13 affected patients revealed a mean age at onset of 43.5 years. The most common neurologic finding was cerebellar ataxia with deep sensory disturbance. Slow saccades was found only in the younger patients below age 35 years. Nerve conduction studies revealed subclinical sensory neuropathy. Brain MRI showed the presence of pontocerebellar atrophy. Genetic study using PCR revealed that all affected patients had an expanded CAG allele in the ataxin-2 gene, which led to a final diagnosis of SCA2. CONCLUSION: SCA2 may be more clinically heterogeneous than previously thought. PCR is useful in differentiating SCA2 from other types of inherited ataxia.
Akabane (AKA) virus is an arthropod-borne virus belonging to the Simbu group of the genus Bunyavirus. Neutralizing monoclonal antibodies (MAbs) against AKA virus were prepared, and the neutralizing epitopes of the virus were defined by competitive binding assay. Five distinct antigenic domains were identified and were designated A, B, C, D, and E. Domains A and C consisted of two epitopes each. It was demonstrated that seven neutralizing epitopes exist on the G1 glycoprotein of AKA virus. Dot immunobinding assays (DIAs) were performed with MAbs which recognize these seven neutralizing epitopes. The results were similar to those obtained by enzyme-linked immunosorbent assay. DIAs were performed using two Australian strains, one isolate from Taiwan, and isolates from Japan collected between the years 1959 and 1994, for a total of 63 isolates. The MAb response patterns were divided into five groups: the OBE-1 strain, the JaGAr39 strain, the Iriki strain, a group which consisted of features between those of the JaGAr39 strain and Iriki strain groups, and a group which did not belong to any of these patterns. The isolates which showed patterns similar to that of the JaGAr39 strain were found mostly among the isolates collected in 1974 and 1990, and isolates with patterns of MAb responses similar to the pattern of the Iriki strain were found mostly in the 1985 isolates. Those showing patterns in between were found mostly around 1977, 1987, and 1994. The results show that DIA can be used to effectively compare the antigenicities of AKA virus isolates within a few hours, even with lesser amounts of virus culture than is required for other assays.
OBJECTIVES: In Japan, hospitals have replaced homes as the predominant site of death, especially for the elderly. Site of death is a reliable indicator of where older people receive care before they die. We conducted a population-based study to identify the factors that determine site of death in a typical rural area in Japan. METHODS: Study subjects were residents of Kawakami town, aged 70 years or older, who died during 1981 and 1990. Death certificates provided information on age, gender, cause of death, duration of illness before death, family members, family occupation, and site of death. RESULTS: Among 455 subjects, 52.7% died at home, while 47.3% died in hospital. Multiple logistic regression analyses indicated that subjects with cancer were 6.1 times more likely to die in hospitals than those with other diseases. Subjects who died in their seventies were 2.3 times more likely to die in hospital than older subjects. Members of non-farming families were 1.7 times more likely to die in hospital than members of farming families. Gender, duration of illness, and the presence of spouse or children in the household were not significantly related to site of death according to multivariate analyses, although trends did exist. CONCLUSION: This case study illustrates the importance of developing geriatric care systems in Japan, utilizing alternatives to hospitals, such as nursing homes and formal home care. This is particularly true for patients with cancer. As the older population rapidly increases in Japan, the need for alternatives in geriatric care grows more critical.
Aneurysms involving the aortic arch were repaired in 12 patients using a technique known as deep hypothermic intermittent circulatory arrest (DHICA). This technique consists of repeated cycles of 20 min of circulatory arrest and 10 min of cerebral and systemic reperfusion. Aneurysms were of the following types: 2 true atherosclerotic aneurysm, 8 aortic dissections, and 2 traumatic aneurysm. There were 2 operative deaths caused by coagulopathy as a result of hepatic failure and difficulty with left ventricular venting. The frequency of circulatory arrest ranged from 2 to 5 cycles, and total circulatory arrest ranged from 20 to 71 min (mean 43.6 min). The lowest tympanic temperature ranged from 17.7 to 19.2 degrees C. No permanent cerebral complications occurred in 10 patients. We believe that this adjunct technique offers excellent results in the surgical treatment of aneurysms involving the aortic arch.
In a previous report we suggested that muscle fibers in distal myopathy with rimmed vacuoles (DMRV) were degraded by both lysosomal proteolysis (cathepsins) and Ca2+-dependent, nonlysosomal proteolysis (calpain). Given recent evidence of abnormal ubiquitin accumulation in rimmed vacuoles, we examined the role of the ATP-ubiquitin-dependent proteolytic pathway (proteasomes) in myofiber degradation in this myopathy. Immunohistochemically, proteasomes (26S) were located in the cytoplasm in normal human muscle, but the staining intensity was weak. Quantitative analysis showed more reactivity for proteasomes in DMRV muscles and, to a lesser extent, in muscles from muscular dystrophy, polymyositis, and amyotrophic lateral sclerosis patients. In DMRV, proteasomes often were located within or on the rim of rimmed vacuoles, and in the cytoplasm of atrophic fibers. Ubiquitin accumulation was marked within rimmed vacuoles and was seen less extensively in the cytoplasm of atrophic fibers. The latter proteins colocalized well. In other diseased muscles, proteasomes and ubiquitin showed a positive reaction in the atrophic or necrotic fibers. The results indicate increased proteasome and ubiquitin in these muscle fibers as well as in other diseased muscle fibers. We suggest that the ATP-ubiquitin-proteasome proteolytic pathway as well as the nonlysosomal calpain and the lysosomal proteolytic pathway may participate in the muscle fiber degradation in DMRV.
A standard reference 10 sample-set of fibrous minerals were prepared by the Japan Fibrous Material Research Association (JFMRA) under the name of JMF standard reference samples. In this paper, the fiber number per unit weight of JFM standard reference samples was determined with a scanning electron microscope. Fiber numbers per unit weight (f/microgram) and standard deviations observed in this experiment were as follows: glass wool (GW1) 7.0 +/- 0.1 x 10(2), rock wool (RW1) 1.7 +/- 0.2 x 10(3), micro glass fiber (MG1) 6.5 +/- 0.4 x 10(4), refractory ceramic fibers; (RF1) 8.8 +/- 0.7 x 10(3), (RF2) 8.7 +/- 0.8 x 10(3), mullite fibers (RF3) 3.5 +/- 0.7 x 10(3), potassium titanate whisker (PT1) 5.9 +/- 0.3 x 10(5), silicon carbide whisker (SC1) 4.1 +/- 0.4 x 10(5), titanium oxide whisker (rutile) (TO1) 6.4 +/- 0.6 x 10(5), and wollastonite (WO1) 2.4 +/- 0.1 x 10(4). Fiber numbers per unit weight would change in proportion to the cube or cube root of the fiber size if the fibers have the same density and the same aspect ratio. JFM standard reference samples should be used taking into consideration the difference in fiber number per unit weight when users conduct in vitro and/or in vivo (injection) biological experiments using these samples.
Lung autopsy specimens were evaluated histologically in the six patients with human T cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM). The results revealed two histologic changes. First, lymphoid infiltrates were distributed widely in peribronchiolar and perivascular regions, subpleural regions, and the alveolus. Lymphoid infiltrates were also observed in bronchial mucosal glands in relatively large bronchi, in which the acinar epithelium was sometimes degenerated. Second, chronic inflammatory changes, such as smooth muscle hypertrophy, fibrosis, or squamous cell metaplasia, were increased significantly in the membranous bronchioles of HAM patients compared with specimens from lung cancer control patients. Such histologic changes were subclinical in most cases, but one case had an abnormal chest shadow, and two cases had recurrent pneumonia. In HAM patients, high levels of HTLV-1-specific cytotoxic T lymphocytes are believed to attack the HTLV-1-bearing cells in the lung, resulting in inflammatory reactions.