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Biomedical subjects

C Hamada

Publications and source records attributed to C Hamada.

At least 37 records · Page 2Linked to original sources

Methylenetetrahydrofolate reductase gene polymorphism and ischemic stroke in Japanese.

Hyperhomocyst(e)inemia has been identified as an independent risk factor for atherosclerotic and thromboembolic diseases such as coronary artery disease, cerebral artery disease, and venous thrombosis. Recently, the alanine/valine (A/V) gene polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR), one of the key enzymes that catalyzes the remethylation of homocysteine, was reported. The VV genotype is correlated with increased plasma homocyst(e)ine levels as a result of the reduced activity and increased thermolability of this enzyme. In this study, we examined the association between the V allele of the MTHFR gene and ischemic stroke in an elderly Japanese population. The diagnosis of cerebral infarction of all study patients was confirmed by CT of the brain. The MTHFR genotype was analyzed by polymerase chain reaction followed by HinfI digestion. In 256 stroke patients and 325 control subjects, the frequencies of the V allele were 0.45 and 0.32, respectively. The odds ratios and 95% confidence intervals adjusted for the other risk factors were, respectively, 1.51 (1.02 to 2.23) for the AV genotype and 3.35 (1.94 to 5.77) for the VV genotype compared with the AA genotype. Both of these effects were statistically significant (P=0.041 and P<0.001, respectively). In patients with multiple infarcts in particular, the allele frequency of the V mutation was 0.56, and the association between the V allele and stroke was highly significant. Plasma homocyst(e)ine levels were significantly higher in patients with the VV genotype than in patients with the AA or AV genotype, especially those with low plasma folate levels. The V allele of the MTHFR gene was significantly associated with cerebral infarction in an elderly Japanese population in a codominant manner. The VV genotype may contribute to risk for ischemic stroke through a predisposition to increased plasma homocyst(e)ine levels, and dietary folate supplementation may be of benefit, particularly to patients with this genotype.

Aged↗

Tree-type algorithm for statistical analysis in chronic toxicity studies.

An appropriate statistical methodology in toxicity studies has been discussed over the last two decades and many statistical methods have already been proposed. Many practical problems, however, still remain unresolved and most pharmaceutical industries have been using a tree-type algorithm routinely to analyze repeated-dose toxicity study data. In considering routine use of statistical analysis in toxicological studies, standardization of statistical methodology is necessary and the decision tree has an important role. In this article, the problems, relating to tree-type algorithms are summarized. Then we propose a new tree-type algorithm, which targets quantitative data in repeated-dose studies in rodents, usually sample size per group between 10 to 20, based on the following two important principles: "using a parametric method" and "suitable for intuition of toxicologists". An example of its application to actual toxicity study data is demonstrated. The performance of this new method is also evaluated using historical data. However, it should be noted that the intention of this paper is not to make a definite solution of the decision tree. Several other alternatives can be considered. Since there is no single theoretically correct solution of tree-type algorithms, too formal a use of the decision tree is not recommended. We must not forget the exploratory nature of evaluating repeated toxicity data.

Algorithms↗

Pharmacokinetics of cefdinir and its transfer to dialysate in patients with chronic renal failure undergoing continuous ambulatory peritoneal dialysis.

Cefdinir (CAS 91832-40-5) was administered orally as a 100-mg capsule (Cefzon) to a total of 12 patients with chronic renal failure undergoing continuous ambulatory peritoneal dialysis (CAPD) to investigate changes in the serum concentrations, excretion rate into the dialysate and serum-protein binding of cefdinir. Cmax values were 1.64-4.34 micrograms/ml, t1/2 values were 10.8-21.9 h., and AUC values were 31.1-73.1 micrograms.h/ml (0-30 h) in four patients given a single oral dose of 100 mg of cefdinir as a capsule. About 1 microgram/ml of cefdinir had still remained in the blood of all the patients 24 h after administration. The serum concentrations of cefdinir were dose-dependent in four patients of each group who were given an oral daily dose of 100 mg for 3 to 8 days and 200 mg (2 capsules) for 4 to 14 consecutive days. No marked change in laboratory test values or clinical symptoms before and after administration were observed in these dose regimes. Protein levels of 5.17-5.71 g/day were eliminated from the peritoneal dialysate and urine. Cefdinir inhibited 90 to 100% of the clinical isolates such as Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and other enteric bacteria causing catheter infection and peritonitis, and its antibacterial activity was stronger than that of amoxicillin (CAS 26787-78-0) or cefaclor (CAS 53944-73-3) against these clinical isolates.

Adult↗

Molecular cloning of the hepatitis A virus receptor from a simian cell line.

Using a eukaryotic expression system in combination with a monoclonal antibody (MAb) capable of blocking hepatitis A virus (HAV) adsorption, a cDNA clone was selected from a library of S.la/Ve-1 cells, a cell line that is highly susceptible to the virus. Sequence analysis of the cDNA revealed a single open reading frame that encoded a protein consisting of 460 amino acids. The deduced primary structure of the protein included a signal sequence, a transmembrane domain, four sites for N-linked glycosylation, cysteine residues attributable to an immunoglobulin domain and threonine clusters characteristic of mucin-like protein. By employing a vaccinia virus expression vector, the cDNA was expressed in HeLa cells where it induced marked HAV attachment which was specifically blocked by the MAb. The cDNA obtained was thus assumed to encode a functional receptor for HAV.

Amino Acid Sequence↗

Surgical resection for small hepatocellular carcinoma.

BACKGROUND: Surgical resection for hepatocellular carcinoma (HCC) can be curative in selected patients, particularly in those with a solitary small HCC (s-sHCC; 2 cm or less in diameter). However, even these patients often have a risk of tumor recurrence or death from underlying liver dysfunction. Therefore it is important to determine which clinicopathologic features are related to the long-term prognosis after resection of s-sHCC. METHODS: Fifty patients with s-sHCC underwent partial hepatectomy at our department between 1977 and 1992. Six (12%) died of liver failure in hospital after operation. Eight clinicopathologic features were examined in the remaining 44 patients with regard to their long-term prognosis by use of univariate and multivariate analyses. RESULTS: The 1-, 3-, and 5-year survival rates were 90%, 75%, and 53%, respectively. The corresponding disease-free survival rates were 80%, 53%, and 30%, respectively. None of the following parameters was significantly related to survival rate or disease-free survival rate: presence of vascular invasion or capsular formation, the distance of free surgical margin (1 cm or more or not), serum alpha-fetoprotein level, positive hepatitis B surface antigen, and preoperative transarterial embolization. Complicated liver function was the only significant factor related to survival rate and disease-free survival rate. CONCLUSIONS: A good hepatic reserve is an important factor in treating patients with s-sHCC by surgical resection, even for a long-term prognosis. Liver transplantation should be considered for patients with severe cirrhosis and s-sHCC, even though a curative resection might be possible.

Adult↗

[Standard range of peak expiratory flow in normal, healthy Japanese subjects].

The measurement and analysis of the standard range of peak expiratory flow (PEF) in normal, healthy Japanese is necessary at any cost to facilitate bringing the Japanese Guidelines for Bronchial Asthma smoothly into effect. In a study as part of The Bronchial Asthma Group of the Comprehensive Research Project (Terumasa Miyamoto, Chairman of the Planning and Evaluation Committee) under the auspices of the Ministry of Health and Welfare, we measured PEF in 2,785 healthy Japanese volunteers (1,407 males aged 15-84 years and 1,738 females aged 15-80 years) who had no history of smoking, respiratory and/or thoracic diseases, or wheezing with four different peak flow meters (e.g., mini-Wright, Assess, Personal Best and Vitalograph). As a result of comparing PEF measured by the four meters in the same subjects over a short interval of time, we noted significant differences on analysis of variance. Accordingly, the equation for prediction should account for variables in gender and the type of peak flow meter used. A comparison of cubic equations for prediction suggests that the PEF of both Japanese men and women is similar to that of the British but is different from that of the Chinese.

Adolescent↗

Circadian changes in urine volume and frequency in elderly men.

PURPOSE: Circadian changes in urinary frequency, diuresis and bladder capacity were evaluated in middle-aged and elderly patients. MATERIALS AND METHODS: A total of 2,703 urinations from 50 men (median age 66 years) was recorded with a 24-hour uroflowmetry system. RESULTS: During a 24-hour period the elderly group showed increased frequency and decreased bladder capacity. No difference was observed in diuresis between the 2 age groups. From midnight to 6 a.m. frequency in the elderly group was significantly greater (p < 0.01) than that in the middle-aged group. CONCLUSIONS: Increased frequency in the elderly group during these hours was primarily due to an increase in diuresis.

Age Factors↗

[Serum levels of remnant-like particles-cholesterol (RLP-C) in patients on hemodialysis].

Serum remnant-like particles-cholesterol (RLP-C), an atherosclerosis risk factor that strongly reflects disorders of chyromicron and VLDL metabolism and contains high levels of TG, was measured in patients on hemodialysis and CAPD. The purpose of this study was to determine the serum levels of RLP-C in 30 outpatients on hemodialysis (18 males, 12 females) and 84 patients on CAPD (53 males, 31 females). The serum RLP-C level was 8.1 +/- 13 mg/dl in CAPD patients and 2.7 +/- 0.2 mg/dl in hemodialysis patients (p < 0.001). Patients who used dialysate containing over 150 g of glucose per day, showed higher levels of serum RLP-C than CAPD patients whose glucose consumption was under 150 g (10.4 +/- 2.4 mg/dl vs. 5.5 +/- 0.6 mg/dl, p < 0.01). There was no statistical relationship between age, sex, dialysis duration and serum RLP-C in CAPD and hemodialysis patients. Serum level of RLP-C was positively correlated with serum triglyceride, total cholesterol, apolipoprotein B and VLDL, and was negatively correlated with apoA-I/apoB in the dialysis patients. It appears that RLP-C, which is one of the risk factors of atherosclerosis, might reflect a disorder of triglyceride metabolism in patients on dialysis, especially on CAPD.

Adult↗

Growth of hepatitis A virus in murine cells.

In order to investigate the growth of hepatitis A virus (HAV) in murine cells, L929 cells of the established mouse cell line were transfected with the virion RNA or infected with the virions and examined for the formation of negative-strand RNA and the rise of the viral infectivity titer. In both the transfected and infected cells, the formation of negative-strand HAV RNA was assayed by the reverse transcription-polymerase chain reaction (RT-PCR). In the transfected cells, infectious HAV of an average titer of 10(1.8) TCID50/dish was obtained. The experiment with the virion infection was further extended by using other mouse cell lines, namely Balb/3T3 clone A31, NIH/3T3, and Swiss/3T3. Here, only NIH/3T3 cells were found capable to support the formation of negative-strand HAV RNA. Thus some murine cell lines are considered to have a complete cellular machinery for supporting the growth of HAV, though the efficiency of virus growth therein was considerably lower as compared to that in the susceptible primate cells.

3T3 Cells↗

[Evaluation of reliability of IPSS by 24-hour uroflowmetry].

BACKGROUND: Although the international prostate symptom score (IPSS) is now often used to assess the symptoms of BPH, whether or not patients answer the questions correctly has not been validated objectively. METHODS: Reliability of IPSS was evaluated by 24-hour uroflowmetry in 20 hospitalized male patients. Six of them had prostatic hypertrophy or cancer, and the evaluation was performed before and after TURP or hormonal therapy in these six patients. The objective scores for frequency and nocturia were obtained from the time recorded on IC card. The objective score for intermittency was calculated from the uroflow curves. RESULTS: The answer about frequency was not correct compared with the objective scores for frequency. The answers about nocturia and intermittency were almost the same as the corresponding objective scores. The answer for weak stream correlated with the average of peak flow rate. However, the threshold of peak flow rate for "weak stream" fluctuated markedly before and after the treatment in the same individuals. The answer for hesitancy had no correlation with the hesitation time. Patients seemed to understand the question translated in Japanese as "have you need force to urinate?" CONCLUSION: Before wider use of IPSS in Japan, the correct translation of the questions and verification of the usefulness of the questions in large number of Japanese patients seem necessary.

Humans↗

Lymph node involvement correlation with survival in advanced gastric carcinoma: univariate and multivariate analyses.

The aim of this study was to elucidate what factors affect the survival of patients with advanced gastric carcinoma. The relationship between the survival of 282 patients over a period of 15 years and 12 prognostic factors was investigated. In univariate analysis, lymph node involvement, depth of invasion, gross form, type of operation, maximum tumor diameter, and lymphatic invasion were found to correlate significantly with survival. Lymph node involvement, gross form, type of operation, and depth of invasion were selected by the Cox proportional hazard model with variable selection methods and found significant. Lymph node involvement was shown to correlate most significantly with survival by both univariate and multivariate analyses. Kaplan-Meier survival curves could indicate that the survival rates of the selected factors were worsening in proportion to the relative risk ratios. These results suggest that further contrivance of therapies should be considered for patients in high risk categories.

Adult↗

Statistical characterization of negative control data in the Ames Salmonella/microsome test.

A statistical characterization of negative control data in the Ames Salmonella/microsome reverse mutation test was performed using data obtained at Takeda Analytical Research Laboratories during January 1989 to April 1990. The lot-to-lot variability of bacterial stock cultures and day-to-day variability of experiments were small for Salmonella typhimurium strains TA1535 and TA1537 and Escherichia coli WP2uvrA, but they were larger for S. typhimurium TA100. The number of revertant colonies for all test strains studied here followed Poisson distributions within the same day. The two-fold rule that is an empirical method to evaluate the Ames Salmonella/microsome test results has been widely used in Japan. This two-fold rule was evaluated statistically. The comparison-wise type I error rate was less than 0.05 for TA98, TA100, TA1535, TA1537, and WP2uvrA. Moreover, this rule is particularly conservative for TA100, for which the type I error rate was nearly 0.

Analysis of Variance↗

Statistical analysis of data in mutagenicity assays: rodent micronucleus assay.

To evaluate chemical safety, many kinds of short-term mutagenicity assays are performed together with long-term assays in animals. Rationales and methodology for these assays have been well discussed and documented. No statistical method, however, has been singled out as the method of choice for the evaluation of mutagenicity assay data, although a number of reports on statistical methods to evaluate such data have been published. Among the mutagenicity assays, the micronucleus assay using mouse bone marrow erythropoietic cells have been widely used to assess cytogenetic activities of test chemicals. A statistical evaluation procedure for this assay is proposed herein, combining the use of historical control data and dose-response relationships. The probability of type I errors and the power of this method are compared with those of some other conventional methods by Monte Carlo simulation.

Animals↗

Purification of blood-group substances in human hepatic bile (HHB) and immunological characterization of anti-HHB serum.

Blood-group substances (BGS) in human hepatic bile (HHB) of blood type A were purified 3657-7314-fold by ethanol sedimentation and column chromatography with DEAE Sephadex A-50 and Concanavalin A Sepharose 4B. An anti-HHB serum was raised by immunizing rabbits with the purified BGS in the HHB. Cross-reactions of the native anti-HHB serum with such human materials as type A blood cell, plasma, seminal fluid and saliva were eliminated by stepwise sequential absorptions with type A red blood cells, type O seminal fluid and type AB plasma. Precipitin titers of the native anti-HHB serum were x 320 and x 80 and those of the absorbed anti-HHB serum x 80 and x 20 against the immunogen and HHB, respectively. Organ and species specificity of the absorbed anti-HHB serum was checked by counter immunoelectrophoresis. It reacted specifically only with the immunogen and HHBs of various ABO blood types. No reactions with animal gallbladder biles were observed. In practical examinations, the specific anti-HHB serum identified 15 out of 20 (75%) HHB samples and 41 out of 46 (89%) human faeces samples. No reactions with animal gallbladder biles and animal faeces were observed.

ABO Blood-Group System↗

Studies of felonious crimes by the University Department of Forensic Medicine in Kumamoto Prefecture, Japan.

This paper gives an understanding of Japan in the respect of forensic medicine. The fight against felonious crimes in Kumamoto is introduced by reference to the police system, crime statistics, an association of police surgeons and medico-legal autopsy in Kumamoto Prefecture. The police have 23 local police stations with 2,670 police officers and the unique Hashutsu-sho and Chyuzai-sho systems. The crime rate is not very high, but crimes committed by Yakuza groups and traffic accidents are major problems in Kumamoto. Medico-legal autopsy is performed in the university department on only criminal and suspected cases after examination of the body externally by a police surgeon. Two illustrative cases are also introduced in this report, which shows good cooperation among the police force, the university department of forensic medicine, and police surgeons in Kumamoto, Japan.

Adult↗

Production of a low molecular weight growth inhibitory factor by adenovirus 12-transformed cells.

Malignant rodent cells transformed by human adenovirus 12 produce a potent cell growth inhibitory factor. The cell growth inhibitory factor inhibits the growth of and DNA synthesis in normal fibroblasts in vitro. Extent of the production of the cell growth inhibitory factor appears to be proportional to that of the malignancy of the transformed cells. C57AT1-AB cells, an adenovirus 12-transformant of C57BL/6 mouse origin, are highly tumorigenic in the syngeneic and allogeneic mice. The cell growth inhibitory factor produced by these cells was characterized for the physicochemical properties; the cell growth-inhibitory activity was quantitatively recovered in the filtrates of YM-2 membrane (M(r) less than 1,000), resistant to the heat treatments at 56 degrees C for 30 min and 100 degrees C for 5 min, and extractable by ethyl acetate under acid-condition. These results suggest that the cell growth inhibitory factor may be lipid or oligopeptides.

Adenoviruses, Human↗

Effects of heparin on osteoclast activity.

The effect of heparin on osteoclastic bone resorption was studied in vitro using the disaggregated osteoclast resorption assay. Bone resorption was assessed by counting the resorption lacunae on bone slices by light microscopy. Low concentrations of heparin (5 micrograms/ml) increased bone resorption by isolated chick and rat osteoclasts. Among other glycosaminoglycans tested at 5 micrograms/ml, only dextran sulfate showed a small but significant stimulation of resorption. Chondroitin sulfates A, B, and C were without effect at 25 and 100 micrograms/ml, whereas resorption was increased by 100 micrograms/ml of heparan sulfate. With chick osteoclasts, which could be maintained in serum-free conditions, a stimulatory effect of heparin was found both in the presence of 5% fetal calf serum and in serum-free media containing insulin, transferrin, and selenium. The magnitude of the heparin-induced increase in resorption was similar in the presence or absence of serum. The stimulation of resorption was associated with an increase in the number of osteoclasts on bone slices. Pretreatment of the bone slices with heparin also enhanced resorption. In time course experiments, 5 micrograms/ml of heparin caused a doubling of chick osteoclast activity index (number of resorption pits per number of osteoclasts) at 12 and 24 h. In 24 h cultures, treatment with 10 micrograms/ml of the arginine-rich basic protein, protamine, 1 microgram/ml of the immunosuppressant, cyclosporine A, or 5 micrograms/ml of the cysteine-proteinase inhibitor, leupeptin, negated the heparin effect on bone resorption. Leupeptin also inhibited basal resorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗