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Biomedical subjects

T Kawai

Publications and source records attributed to T Kawai.

At least 73 records · Page 4Linked to original sources

Ultrasound vasography evaluation of radial arterial grafts used for coronary arterial bypass surgery.

OBJECTIVES: For coronary bypass surgery, radial arteries are often used as bypass grafts. Some of these arteries however, have arteriosclerotic lesions. We attempted to evaluate the relationship between arteriosclerosis and vasodilation. METHODS: Prior to bypass surgery, 20 patients underwent ultrasound vasography to determine the condition of their radial and brachial arteries. Flow-mediated dilation, which is the same as endothelium-dependent vasodilation, was measured in the brachial artery of the nondominant arm by reactive hyperemia after 5-minute forearm ischemia. Vasodilation after application of a sublingual glyceryl trinitrate spray was also measured. RESULTS: During surgery, 4 of 20 radial arteries demonstrated calcification, and 3 of the 4 could be used by removing the calcified part. However, the other artery, which had extensive calcification that could not be detected by ultrasound vasography, was discarded. The amount of vasodilation seen after the administration of sublingual glyceryl trinitrate had no correlation with calcified grafts. Calcified radial arteries demonstrated significantly poor brachial artery vasodilation by an endothelial-dependent vasodilation test. CONCLUSIONS: Calcification in radial arteries can thus only be evaluated by flow-mediated dilation.

Aged↗

Pedunculated hemangioma in the right ventricle.

We report a rare case of right ventricular hemangioma. In an asymptomatic 56-year-old man, echocardiography as a part of medical checkup demonstrated a pedunculated tumor, 1.0 x 1.3 x 1.5 cm, arising from the free wall of the right ventricle. No findings were seen of a feeding artery to the tumor or vascular blush in preoperative coronary angiography. Successful resection was done through right atriotomy under total cardiopulmonary bypass. The histological examination revealed capillary hemangioma. The postoperative clinical course was uneventful, but requires careful follow-up for possible coronary cardiac fistula. This is the fifth case of right ventricular hemangioma, to our knowledge, ever reported in Japan.

Heart Neoplasms↗

Urinary bromide levels probably dependent to intake of foods such as sea algae.

The purpose of the present study is to examine if the bromide (Br) level in urine (Br-U) varies substantially among adult general populations of either sex or of different dietary habits. For this purpose, morning spot urine samples (about 50 per group) were collected from six groups of people, i.e., one group each of men and women in a city in Japan (thus two groups in Japan) and one group each of women in two urban and two rural areas in central and northeast China (four groups in China). The samples were analyzed for Br by ECD-gas chromatography after derivatization to methyl bromide. Br-U essentially followed a normal distribution. Whereas there was only a marginal difference in Br-U between men (7.7 +/- 2.5 mg/L as an arithmetic mean and arithmetic standard deviation) and women (8.1 +/- 2.9 mg/L) in Japan, and no difference between the urban (2.3 +/- 0.8 mg/L) and rural women (2.6 +/- 1.1 mg/L) in China, the difference between Japanese (8.1 +/- 2.9 mg/L) and Chinese women (2.3 +/- 0.8 mg/L for two cities and 2.6 +/- 1.1 mg/L for two villages) was substantial. A literature survey suggested variation in dietary habits, especially that in sea algae intake, is a possible factor affecting the observed difference in Br-U between the two ethnic groups. Contribution of Br in cereals after fumigation with, e.g., methyl bromide, was also thought to be possible. The implication of difference in background Br-U levels is discussed in relation to biological monitoring of exposure to Br-containing industrial chemicals, such as 1- and 2-bromopropane.

Adult↗

Changes in atrial natriuretic peptide and brain natriuretic peptide associated with hypobaric hypoxia-induced pulmonary hypertension in rats.

Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodeling of the heart and pulmonary arteries. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) both have diuretic, natriuretic, and hypotensive effects, and both are involved in cardiovascular homeostasis as cardiac hormones. To study the effects of HHE on the natriuretic peptide synthesis system, 170 male Wistar rats were housed in a chamber at the equivalent of the 5500-m altitude level for 1-12 weeks. After 1 week of HHE, pulmonary arterial pressure was significantly raised, and the ratio of left ventricle plus septum over right ventricle of the heart showed a significant decrease (compared with those of ground-level control rats). In both ventricular tissues, the expression of ANP messenger (m)RNA and BNP mRNA increased after exposure to HHE. The amounts of ANP and BNP had decreased significantly in right atrial tissue at 12 weeks of HHE (compared with those of the controls), whereas in ventricular tissues at the same time point, both levels had increased significantly. In in situ hybridization and immunohistochemical studies, the staining of the mRNAs for ANP and BNP and of ANP and BNP themselves was more intense in both ventricular tissues after exposure to HHE than before (i.e., in the controls). The results suggest that, in response to HHE, the changes in ventricular synthesis are similar for ANP and BNP. These changes may play a role in modulating pulmonary hypertension in HHE. However, under our conditions, pulmonary hypertension increased progressively throughout the HHE period.

Altitude Sickness↗

Expression and distribution of beta amyloid precursor protein and beta amyloid peptide in reactive astrocytes after transient middle cerebral artery occlusion.

BACKGROUND: In the brains of Alzheimer's disease patients, beta amyloid protein is the major component of senile plaque. In ischemic stress, beta amyloid precursor protein (APP) and beta amyloid peptide are reported to be upregulated. METHOD: Using Male Wistar-ST rats, expression and distribution of APP and beta amyloid peptide were examined immunohistochemically after transient ischemia induced by a 2-h middle cerebral artery occlusion (MCAO). After reperfusion for 3, 7, 14, 30 and 60 days, brains were removed and immunostaining was performed. FINDINGS: The reactive astrocytes with APP were observed in the periphery of infarct from 3 days to 60 days post-occlusion. The immunoreactivity of beta amyloid peptide was also localized in the reactive astrocytes in the peripheral zone of infarct at 7, 14, and 30 days post-occlusion. However, beta amyloid expression was not identified at 3 days or 60 days post MCAO. Transient ischemia temporarily induced beta amyloid peptide expression in reactive astrocytes, but this expression peaked at 30 days and disappeared at 60 days. INTERPRETATION: These findings suggested that beta amyloid peptide was derived from the processing of APP produced in the same reactive astrocytes and the production of the peptide stopped within 60 days after the ischemic stress.

Alzheimer Disease↗

Expression of matrix metalloproteinases in invasive pulmonary adenocarcinoma with bronchioloalveolar component and atypical adenomatous hyperplasia.

To investigate the association between the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) and the clinicopathological features in lepidic and invasive components of adenocarcinoma of the lung, we performed immunostaining for type IV collagen, various MMPs, and TIMPs in 27 cases of invasive adenocarcinomas and 5 cases of atypical adenomatous hyperplasia of alveolar epithelial cells (AAH). Mean extent of lepidic growth was 61% and the survival was significantly better in cases with 50% or more lepidic component. The preservation of type IV collagen in lepidic areas correlated inversely with lymphatic or vascular invasion (P = 0.02 and 0.002, respectively). Five-year survival was reduced in cases showing destruction of type IV collagen (P = 0.004) or expression of MMP-2 (P = 0.008) in lepidic areas. MMP-2 co-localized with MT-1-MMP (its activating enzyme) and TIMP-2 in neoplastic cells. Reactivity for other MMPs and TIMPs did not correlate with destruction of type IV collagen or prognosis. Type IV collagen was preserved in all cases of AAH. MMP-2, but not MT-1-MMP, was expressed in two of the five cases of AAH. Immunostaining for type IV collagen MMP-2 is useful in evaluating the prognosis of the lung.

Adenocarcinoma, Bronchiolo-Alveolar↗

A field evaluation of in situ biodegradation of trichloroethylene through methane injection.

A field study of biodegradation of trichloroethylene (TCE) through methane injection was conducted at the yard of a home in Japan. Methane was selected as the safest substrate for injection into groundwater. Methane, oxygen, nitrate, and phosphate were introduced into groundwater contaminated with 220 microg/L of TCE. After a week of biostimulation, methane concentrations gradually decreased below the detection limit. Methane oxidizing bacterial numbers increased from 10 to 10(4) cells/mL with methane consumptions. During methane injection. 10-20% of TCE removal was observed. The biotransformation yield was 3-13 mgTCE/gCH4 in this field test. After methane injections were stopped, TCE removal was not observed. These results indicated that bioremediation using methane was useful as a safe technology for a TCE-contaminated area near homes.

Biodegradation, Environmental↗

Chronic effects of different fatty acids and leptin in INS-1 cells.

The effects of long-term exposure of a pancreatic beta cell line, INS-1, to major free fatty acids (FFA; palmitic acid, oleic acid and linoleic acid) and leptin on insulin secretion and cell viability by C,N-diphenyl-N'-4,5 dimethylthiazol 2-yl tetrazolium bromide (MTT) assay were examined. The cells were incubated with 1 mmol/l of each FFA and 25 or 100 ng/ml leptin, alone or in combination, for 4, 24 or 48 h before the insulin secretion experiments. Palmitic acid (C 16:0) significantly suppressed cell viability, and suppressed insulin secretion at 24 h. Treatment with oleic acid (C 18:1) or linoleic acid (C 18:2) enhanced basal insulin secretion and diminished glucose-stimulated insulin secretion (GSIS) at 48 h. In these groups, there were no differences in cell viability as compared to cells treated without FFA. Leptin did not affect insulin secretion at 4, 24 and 48 h, and in the cells co-treated with FFA and leptin, leptin did not ameliorate lipotoxicity. These results suggest that, in INS-1 cells, different FFA have different patterns of lipotoxicity with chronic exposure, and leptin has little direct effect on insulin secretion.

Animals↗

Reduced neuropeptide Y mRNA levels in the frontal cortex of people with schizophrenia and bipolar disorder.

To study the change of gene expression in the brain tissues of schizophrenia, we used the gene expression monitoring technology and compared two sets of pools each containing four RNA samples of frontal cortex that were randomly selected from the control or schizophrenia group. We found that the expression of two genes were commonly altered in four pairwise comparisons; the expression of DEAD-box protein p72 (p72) gene was increased and neuropeptide Y (NPY) gene expression was decreased in the schizophrenia group compared with the control group. To substantiate these results, we estimated their mRNA levels by the real time TaqMan method in the 15 samples of each frontal or temporal cortex of four matched groups of schizophrenia, bipolar disorder, major depression and normal controls. A statistically significant decrease was observed for NPY in the frontal, but not in the temporal cortex, in the schizophrenia group (P=0.003). A decrease was also observed in the frontal cortex of the bipolar disorder group (P=0.031). In contrast, p72 gene expression showed no significant difference among the four groups. In conclusion, by novel technology of DNA array and TaqMan PCR analyses, we found that neuropeptide Y mRNA levels were significantly reduced in the frontal cortex in both schizophrenia and bipolar disorder.

Journal Article↗

Expression of p27(Kip1) protein in transitional cell carcinoma of the upper urinary tract.

The expression of p27(Kip1), a negative regulator of the cell cycle, has been reported to correlate with the biological behavior and prognosis of several tumors. However, its prognostic importance in transitional cell carcinoma of the upper urinary tract (TCC-UUT) has not previously been investigated. We investigated p27(Kip1) protein expression using immunohistochemistry in 132 cases of TCC-UUT and also its relation to proliferating cell nuclear antigen (PCNA) immunoreactivity, p53 oncoprotein immunoreactivity, clinicopathologic parameters, and clinical outcome. A positive expression of p27(Kip1) protein was recognized in 94.7% of the samples and was apparent within tumor nuclei. In the normal urothelium, its expression was identified in all cell layers. A positive expression of p53 oncoprotein was recognized in 27.2% of the patients. The PCNA index was 7.4 to 93.1% (mean, 66.4%). Examination of the relationships between the expression of p27(Kip1) protein and clinicopathologic findings, PCNA index, and the expression of p53 oncoprotein revealed that the expression of p27(Kip1) protein decreased significantly with stage and grade. In a univariate analysis of disease-free and overall survival rates, no correlation was found between the expression of p27(Kip1) protein and prognosis. The expression of p27(Kip1) protein appears to be of little or no value in informing the prognosis in TCC-UUT.

Adult↗

Expression of telomerase catalytic subunit (hTERT) mRNA does not predict survival in patients with transitional cell carcinoma of the upper urinary tract.

Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric repeats onto chromosomal ends using a segment of its RNA component as a template. Its activity has become an established indicator of the diagnosis, biological behavior, and prognosis of several tumors. However, few studies have investigated the diagnostic and prognostic importance of the expression of telomerase catalytic subunit (hTERT) mRNA in transitional cell carcinoma of the upper urinary tract (TCC-UUT). We investigated the expression of hTERT mRNA using in situ hybridization in 125 cases of TCC-UUT, and also its relation with the expression of telomerase RNA component (hTERC), proliferating cell nuclear antigen (PCNA) immunoreactivity, clinicopathologic parameters, and clinical outcome. A positive expression of hTERT mRNA was recognized in 93.6% of the samples and was apparent within the cytoplasm of tumor cells. In the normal urothelium examined in a few cases, its expression was barely detected. hTERT mRNA scores showed a significant association with hTERC score. However, no relationship was found between the expression of hTERT mRNA and clinicopathologic findings, PCNA index, or prognosis. These results suggest that the expression of hTERT mRNA does not predict prognosis in TCC-UUT.

Adult↗

Relationships between baseline serum leptin levels and 2-year changes in body mass index, blood pressure and metabolic parameters in Japanese male adolescents and middle-aged men.

We and others have reported that serum leptin levels are positively correlated with body mass index (BMI), blood pressure and heart rate (HR) in cross-sectional clinical studies. However, only a few longitudinal studies have focused on the relationships between leptin, BMI and blood pressure. The present study was performed to elucidate the relationships between baseline serum leptin levels and 2-year changes in BMI, blood pressure, HR and metabolic parameters in 314 Japanese male adolescents aged 16-17 years and in 225 Japanese men aged 30-63 years. Height, weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), HR, fasting plasma glucose (FPG), serum lipids [total cholesterol (TC), triacylglycerols (TG), high-density-lipoprotein cholesterol (HDL-C) and low-density-lipoprotein cholesterol (LDL-C)], uric acid (UA), insulin and leptin levels were measured in the morning after an overnight fast. In the male adolescents, serum leptin levels in 1996 (log[leptin'96]) were significantly correlated with BMI, SBP, mean blood pressure and HR in 1998 (r=0.40, 0.13, 0.11 and 0.14, respectively). The percentage change in BMI per year (DeltaBMI) was negatively correlated with log[leptin'96], even after adjustment for baseline BMI (r=-0.12, P=0.030). In men aged 30-63 years, log[leptin'96] was also positively correlated with BMI'98, SBP'98, DBP'98, FPG'98, TC'98, log[TG'98], LDL-C'98 and UA'98 (all P<0.05), and negatively correlated with HDL-C'98, DeltaBMI, DeltaFPG, DeltaTC and DeltaLDL-C. The relationship between log[leptin'96] and DeltaTC was significant, even after adjustment for initial BMI (r=-0.15, P=0.023). These findings therefore suggest that serum leptin levels are correlated with subsequent decreases in BMI and TC in Japanese men.

Adolescent↗

Telomerase activity and expression of human telomerase RNA component and human telomerase reverse transcriptase in lung carcinomas.

The aim of this study was to evaluate the usefulness of determination of telomerase activity and expression of human telomerase RNA component (hTERC) and human telomerase reverse transcriptase (hTERT) for the diagnosis of lung carcinomas. The tissues studied consisted of 115 carcinomas and adjacent nonneoplastic lung, which were removed surgically without previous chemotherapy or radiotherapy. Telomerase activity was determined using a semiquantitative polymerase chain reaction-based telomeric repeat amplification protocol (TRAP) assay. The results obtained were classified into high and low telomerase groups. Localization of expression was examined by using in situ hybridization and immunohistochemistry. The correlation between telomerase activity in lung carcinoma and clinicopathologic features, including prognosis, was investigated. Telomerase activity in lung carcinomas was detected in 107 of 115 (93%) lung carcinomas, but not in any adjacent noncancerous tissues, and was significantly higher in small cell carcinoma than in any other histologic type. This activity also was significantly higher in poorly differentiated than in well-differentiated squamous cell carcinomas and adenocarcinomas. The overall survival rate (P =.020) was significantly lower in the high telomerase group. Messenger RNAs for hTERC and hTERT were mainly detected in the cytoplasm of cancer cells by in situ hybridization, and TERT protein was localized in the nuclei of these cells by immunohistochemical staining. Determinations of telomerase activity by in situ hybridization, immunohistochemistry, and TRAP assay are useful for evaluating the diagnosis and prognosis of lung carcinomas.

Adenocarcinoma↗

Effects of intestinal fatty acid-binding protein gene Ala54Thr polymorphism and beta3-adrenergic receptor gene Trp64Arg polymorphism on insulin resistance and fasting plasma glucose in young to older Japanese men.

The present study was performed to investigate the effects of the intestinal fatty acid-binding protein (FABP2) gene Ala54Thr polymorphism and the beta(3)-adrenergic receptor (beta3AR) gene Trp64Arg polymorphism on body mass index (BMI), blood pressure, heart rate, glucose and lipid profiles, and serum leptin level in 196 young men aged 21 to 39 years, 186 older normoglycemic men (fasting plasma glucose [FPG] < 110 mg/dL) aged 40 to 65 years, and 122 older hyperglycemic men, including 77 type 2 diabetic patients. Genomic DNA was extracted from the peripheral blood, and these polymorphisms were assessed by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. In the older groups, the beta3AR Arg64-allele frequency tended to be lower and the FABP2 Thr/Thr54 genotype frequency tended to be higher in hyperglycemic patients, although these differences did not reach statistical significance. Also, there were no significant differences in the genotype or allele frequency of either variant between the 27 hyperlipidemic and 204 normolipidemic subjects. In the younger group, there were no significant differences in any of the parameters measured between the genotypes of beta3AR or FABP2. In the older normoglycemic subjects, heart rate was significantly lower (P =.037) in beta3AR Arg64-positive subjects, and FPG was significantly higher in subjects with the FABP2 Thr/Thr genotype than the other genotypes (99.8 +/- 5.6 v 96.5 +/- 5.6 mg/dL, P =.010). In the older hyperglycemic group, the beta3AR Arg64-positive group had significantly lower high-density lipoprotein (HDL) cholesterol and free fatty acid (FFA) levels (P =.024 and P =.043, respectively). There were no synergistic effects of these 2 variants on any measured parameter, but only the FABP2 Thr/Thr genotype was related to a higher FPG in the older normoglycemic men. In conclusion, no major difference was associated with the beta3AR Trp64Arg or FABP2 Ala54Thr polymorphism in terms of type 2 diabetes or hyperlipidemia in young to older Japanese men. However, a slight but significant increase in FPG was observed in older Japanese men with the FABP2 Thr/Thr genotype.

Adult↗

Survey of congenital anomalies associated with cleft lip and/or palate in 701,181 Japanese people.

There have been many reports on congenital anomalies associated with cleft lip and/or palate (CL/CLP) in Japan. However, these reports included data only on patients who came to hospitals; thus the real situation regarding these anomalies remains unclear. Therefore, we surveyed newborns at all delivery facilities in the central area of Japan for the presence of these anomalies, following their progress for 12 consecutive years; at the end of that time, questionnaires were collected and analyzed. In this article, we describe our results.

Birth Weight↗

Discrimination of bacterial lipoproteins by Toll-like receptor 6.

Bacterial lipoproteins (BLP) trigger immune responses via Toll-like receptor 2 (TLR2) and their immunostimulatory properties are attributed to the presence of a lipoylated N-terminus. Most BLP are triacylated at the N-terminus cysteine residue, but mycoplasmal macrophage-activating lipopeptide-2 kD (MALP-2) is only diacylated. Here we show that TLR6-deficient (TLR6(-/-)) cells are unresponsive to MALP-2 but retain their normal responses to lipopeptides of other bacterial origins. Reconstitution experiments in TLR2(-/-) TLR6(-/-) embryonic fibroblasts reveal that co-expression of TLR2 and TLR6 is absolutely required for MALP-2 responsiveness. Taken together, these results show that TLR6 recognizes MALP-2 cooperatively with TLR2, and appears to discriminate between the N-terminal lipoylated structures of MALP-2 and lipopeptides derived from other bacteria.

Animals↗

The effect of heat-treated human bone morphogenetic protein on clinical implantation.

For the clinical usage of human-derived bones, it is necessary to treat bones to reduce the risk of contamination by microorganisms. Bone morphogenetic protein is vulnerable to chemicals, but shows resistance to thermal heat to 70 degrees C in a short time. In this experiment, crude human bone morphogenetic protein was extracted from heat-treated bones at 60 degrees C for 10 hours and from nonheated bones. Sodium dodecyl sulfate polyacrylamide gel electrophoresis for these specimens was done. Gelatin capsules containing 5 mg of crude human bone morphogenetic protein extracted from heated and nonheated bones were implanted into thigh muscle pouches of five mice. At 20 days after implantation, the heterotopic bone formation was compared by evaluating the radiographic and histologic analyses. The sodium dodecyl sulfate polyacrylamide gel electrophoresis pattern of the human bone morphogenetic proteins showed five main bands (16, 22, 28, 35, and 67 kDa) that were almost identical. Heterotopic bone formation observed on the radiograph was induced by crude human bone morphogenetic protein from heated bones in a manner similar to that used for nonheated bones. The results from this study show that heat-treated bone preserves osteoinduction.

Animals↗