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Biomedical subjects

T Kawamoto

Publications and source records attributed to T Kawamoto.

At least 145 records · Page 8Linked to original sources
PubMed1997

Hepatocyte growth factor in bronchoalveolar lavage fluids and cells in patients with inflammatory chest diseases of the lower respiratory tract: detection by RIA and in situ hybridization.

Pulmonary fibrosis is a chronic inflammatory disorder characterized by diffuse fibrous remodeling of alveolar spaces. Although much interest is focused on mechanisms of the inflammatory process in pulmonary fibrosis, little is known about the repair and regenerative process. Hepatocyte growth factor (HGF), originally discovered as a mitogen for hepatocyte regeneration, is now recognized as a multifunctional mesenchymal factor for epithelial regeneration, including the regeneration of alveolar type II epithelial cells. Involvement of HGF and its receptor (c-met) is evident in animal models of acute lung injury produced by hydrochloride inhalation. We studied the role of HGF in patients with idiopathic pulmonary fibrosis (IPF) (25 cases), lung fibrosis associated with rheumatoid arthritis (22 cases), and sarcoidosis (39 cases). Immunohistochemical evaluation demonstrated that hyperplastic alveolar type II epithelial cells, as well as alveolar macrophages, were strongly stained with anti-HGF antibody in tissues of patients with IPF. The concentration of HGF in bronchoalveolar lavage fluid (BALF) was significantly higher than in normal controls (0.23 +/- 0.09 pg/microg) in patients with IPF (0.77 +/- 0.88 pg of HGF/microg of albumin, P < 0.001), lung fibrosis associated with rheumatoid arthritis (0.50 +/- 0.64 pg/microg, P < 0.01), and sarcoidosis (0.41 +/- 0.61 pg/microg, P < 0.05). In situ hybridization revealed mRNA for HGF in alveolar macrophages (especially small monocytelike macrophages). These results indicate that the increase in HGF concentration in patients' peripheral air spaces is due to augmented HGF production by alveolar epithelial cells and alveolar macrophages. HGF, through a paracrine mechanism, may play an important role in the repair and healing of the inflammatory lung damage in pulmonary fibrosis.

Adult↗
PubMed1997

Pathway and speed of calcium movement from blood to mineralizing enamel.

We studied by autoradiography the distribution of 45Ca in the enamel organ of frozen rats 4.3, 6.1, 7.8, 10.6 and 13.7 sec after an i.v. injection. The intercellular junctions of the proximal side of the smooth-ended ameloblast (SA) and the distal side of the ruffle-ended ameloblast (RA) were closed to calcium. The junctions of the distal side of SA, the proximal side of RA, and both sides of the secretory stage ameloblasts were not. The time required for calcium to pass through the ameloblast layer was less than 1.8 sec in the secretory stage and SA region. The time in the RA region was 3.5-6.3 sec. In the transitional region from RA to SA, a band of strong radioactivity appeared from the papillary layer of RA region towards the enamel of the SA region. The radioactivity in the secretory stage enamel increased almost linearly with time. The diffusion speed of calcium in the enamel was more than 50 microns for 1.8 sec in the maturation stage and less than 15 microns for 9.4 sec in the secretory stage. These results indicate that in the secretory and SA regions calcium moves to the enamel surface through the intercellular spaces of ameloblasts and in the RA region via RA cells.

Ameloblasts↗
PubMed1997

[Protective effect of L-histidine (singlet oxygen scavenger) on transient forebrain ischemia in the rat].

Histidine is an efficient scavenger of highly active singlet oxygen and somewhat weaker scavenger of hydroxyl radicals. And it has been shown to protect against reperfusion injury in the heart. The effects of L-histidine were examined in the forebrain ischemia reperfusion injury of the rat hippocampus (CA-1). Male Wistar rats were treated with the free radical scavenger L-histidine for 30 minutes before transient forebrain ischemia produced by 4-vessel occlusion. The extracellular concentrations of glutamate were measured by cerebral microdialysis. The intravenous (i.v.) administration of 50 mg/kg and 100 mg/kg L-histidine protected the elevation of extracellular glutamate concentrations after transient cerebral ischemia (p < 0.01). And the administration of L-histidine prevented ischemia-reperfusion induced delayed neuronal death in the rats. Morphological changes in the CA-1 sector of the hippocampus were evaluated 7 days after 10 minutes occlusion. The average neuronal density of treated groups showed a statistically significant (p < 0.01) persistence compared with that of control groups. These results indicate that L-histidine can reduce neuronal damage after reperfusion of cerebral ischemia and further suggest that excitatory amino acid and oxygen free radicals may damage the brain by a common pathway.

Animals↗
PubMed1997

[Transthoracic digital color Doppler assessment of the left anterior descending coronary artery and intramyocardial blood flow].

Noninvasive assessment of the distal left anterior descending coronary artery and intramyocardial blood flow were attempted in 50 consecutive patients (28 males and 22 females, mean age [+/-SD] 58 +/- 12 years) using a 7.5 MHz transducer (Doppler frequency: 5 MHz) and a SSA-380A ultrasound digital system with special optimal settings for the color Doppler examination. Modified apical acoustic windows were used to visualize the blood flow in the distal left anterior descending coronary artery and the intramyocardial artery. By selecting a sample volume (2 mm wide) on the color trace of these blood flows, Doppler spectral tracing of the distal left anterior descending coronary artery and intramyocardial blood flows could be recorded using pulsed-wave Doppler system. Blood flow in the distal left anterior descending coronary artery was detected in 43 (86%, Vmax = 22 +/- 8.7 cm/sec, Vmean = 16 +/- 5.1 cm/sec) of 50 patients, and intramyocardial blood flow in 40 (80%, Vmax = 26 +/- 11.0 cm/sec, Vmean = 19 +/- 8.5 cm/sec) of 50 patients. Distal left anterior descending coronary artery and the intramyocardial blood flows can be imaged by transthoracic digital color Doppler echocardiography in the clinical setting.

Coronary Circulation↗
PubMed1997

[Measurement of plaque volume using three-dimensional intravascular ultrasound: in vitro study].

The usefulness of three-dimensional echocardiography using intravascular ultrasound (3D-IVUS) for the measurement of plaque volume was evaluated by comparing plaque volume derived from 3D-IVUS with that directly measured in 10 autopsied iliac or femoral plaque models (5-15 mm long). Using IVUS (3.5 F, 30 MHz), sequential cross-sectional images for three-dimensional datasets were acquired with a motorized catheter pullback device connected to the three-dimensional reconstruction system. Three-dimensional reconstruction was performed from the sum of the two-dimensional cross-sectional views. Plaque volumes were calculated using a summation of disks algorithm based on the reconstructed multiple short-axis cross-sections from the three-dimensional data. Three-dimensional IVUS demonstrated a good correlation with direct measurement of plaque volume (y = 0.71x + 0.001, r = 0.80, SEE = 0.003 ml), so is useful for the measurement of plaque volumes in the experimental models.

Arteriosclerosis↗
PubMed1997

Comparison of acid anhydrides with carboxylic acids in enantioselective enzymatic esterification of racemic menthol.

Optical resolution of racemic menthol has been efficiently achieved by lipase-catalyzed enantioselective esterification in an organic solvent. The performance of the reaction using an acid anhydride as an acyl donor was compared with that using its corresponding free acid. The reactivities of acid anhydrides were found to be higher than their corresponding free acids, but acid anhydrides were also found to be easily hydrolyzed into free acids under the catalysis of the same enzyme. The existence of a too-high concentration of an acid anhydride in a micro-aqueous reaction system will cause dehydration and thus deactivation of the enzyme, and will enhance non-selective esterification of a chiral alcohol, which will reduce the optical purity of the product. All these drawbacks, however, could be effectively overcome in a semi-batch reaction system into which propionic anhydride was continuously fed. This system showed some advantages over a batch reaction system using free propionic acid: the reaction time of dl-menthol was shortened by half, the stability of the enzyme was much enhanced, and the optical purity of the product (l-menthyl ester) was kept at a similarly high level (> 98% ee).

Acids↗
PubMed1996

DNA binding of PhoB and its interaction with RNA polymerase.

We have identified the DNA-binding domain (DBD) of an Escherichia coli activator protein PhoB as its C-terminal 91 residues. Four amino acid positions in the PhoB DBD are found important for interaction with the RNA polymerase holoenzyme that contains the sigma 70 subunit. Assuming that the PhoB DBD is structurally similar to the histone H5 DBD, the four positions are placed around the turn region that connects two putative helices, 2 and 3 (helix 3 is likely to be the recognition helix). The binding sites of PhoB, three with the sequence TGTCA and one of TTACA, are identified in the pstS promoter. The pstS promoter has intrinsic bending (or bendability), which is much enhanced upon binding PhoB. On the basis of the above, some aspects of the PhoB-DNA-RNA polymerase interaction are discussed.

Amino Acid Sequence↗
PubMed1996

Habitual and genetic factors that affect urinary background levels of biomarkers for organic solvent exposure.

Urinary hippuric acid, phenol, and o-cresol, which are biomarkers for toluene, benzene, and phenol exposures, are usually present in a significant amount in urine collected from subjects who have not been occupationally exposed to the organic solvents. With the improvement of working environments, the urinary concentrations of the biomarkers have become lower and closer to the levels of urine from unexposed subjects. It is very useful to clarify the background levels of these biomarkers and the factors which effect the background levels of the biomarkers in order to make effective use of biological monitoring under low level exposure. In the present study, the effects of life habits and the genetic polymorphisms of the metabolizing enzymes on the background levels of urinary hippuric acid, phenol and o- and p-cresol were clarified, using 351 males (means age: 38.6, range: 19-71) who were not occupationally exposed to hazardous chemical materials. Their life habits, smoking, alcohol consumption, and dietary habits were examined by means of a questionnaire. The genotypes of five metabolizing enzymes, that is, low Km aldehyde dehydrogenase (ALDH2), polymorphic N-acetyl transferase (NAT2), cytochrome P-4501A1 (CYP1A1), cytochrome P-4502E1 (CYP2E1), and glutathione-S-transferase mu (GSTM1) were determined form peripheral blood samples. The urinary hippuric acid and creatinine were analyzed by HPLC and urinary phenol, o-, p- and m-cresol were determined by GC/MS. Recoveries and the coefficients of variance of phenol, o-cresol, and p-cresol ranged from 92.7 to 107.8% and 1.3% to 6.7%, respectively. Linear relationships between the concentrations of phenol, o- and p-cresol, and their peak area ratios were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyltransferases↗
PubMed1996

Effects of cyclic adenosine 3',5'-monophosphate on chondrocyte terminal differentiation and cartilage-matrix calcification.

We examined the effects of cyclic AMP on terminal differentiation and calcification in rabbit growth plate chondrocyte cultures. Dibutyryl cAMP (dbcAMP), as well as 8-bromo-cAMP abolished the increases in chondrocyte size, alkaline phosphatase activity, type X collagen synthesis, 1 alpha, 25-dihydroxyvitamin D3 receptor synthesis, the incorporation of 45Ca into insoluble material, and the calcium content. All of these occurred in parallel untreated cultures during the hypertrophic (terminal) stage. The inhibition of alkaline phosphatase by dbcAMP was detectable after 24 h, and this effect was reversible. dbcAMP and 8-bromo-cyclic AMP inhibited alkaline phosphatase induction and calcification at low concentrations (3-5 microM), whereas 10-30-fold higher concentrations were required to stimulate proteoglycan synthesis. These findings suggest that cAMP plays a crucial role in suppressing terminal differentiation of chondrocyte and cartilage-matrix calcification.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Intra-abdominal fat, lipid metabolism and insulin resistance in coronary artery disease.

To investigate the metabolic and atherogenic effect of intra-abdominal fat accumulation, we examined correlation between variables of lipid and glucose and the fat distribution of abdominen by using computed tomography. Subjects were 292 of male and 161 of female who underwent coronary angiography. Intra-abdominal fat area was correlated with insulin concentration at 120 min in oral glucose tolerance tests and triglyceride level in male, on the other hand, in female were HDL-cholesterol level, apolipoprotein B, glucose area under curve and insulin concentration at 60 and 120 min. In an aspect of atherogenic effect of intra-abdominal fat, it was not atherogenic in isolated state in male, but atherogenic in diabetic female. Intra-abdominal fat was accompanied with hypertension and mid-band, which appeared between alpha and beta band in polyacrylamide diskgel electrophoresis. Cluster of intra-abdominal fat accumulation, hypertension and mid-band was atherogenic in male, in which insulin resistance play an important role in the coronary artery disease. On the contrary, intra-abdominal fat accumulation accompanied with exacerbation of glucose tolerance, hypertensive and high level of apolipoprotein B in female. We concluded that visceral fat accumulation was a generator of metabolic syndrome X in male and was a progression factor for diabetes, hypertensive and high apolipoprotein B level in female.

Abdomen↗
PubMed1996

Phase II study of DTIC, ACNU, and vincristine combination chemotherapy for supratentorial malignant astrocytomas.

This phase II clinical study evaluated the use of 5-(3-3'-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) pretreatment to reduce cellular resistance and enhance the antitumor effects of chloroethyl nitrosoureas in 32 patients with supratentorial malignant gliomas, including 13 anaplastic astrocytoma and 19 glioblastoma multiforme. All patients received a total dose of 50-65 Gy radiation therapy after surgery. Chemotherapy consisted of DTIC (1 mg/kg) on days 1-5, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (2 mg/kg) on day 5, and vincristine (0.02 mg/kg) on days 1 and 15 every 5 weeks. One patient achieved complete response and 12 patients showed partial response. Median survival time was 18 months and median time-to-progression was 11 months. No significant toxicity was encountered. There was no significant benefit of this pretreatment to combination chemotherapy when compared with previous results. This study does not support a further role for DTIC as a depleter of O6-alkylguanine deoxyribonucleic acid alkyltransferase activity preceding chloroethyl nitrosourea-based chemotherapy.

Adolescent↗
PubMed1996

Indoor pollution from heating.

The concentrations of indoor pollutants generated from types of heaters were measured in a model room of 20m2 in area and 45m3 in capacity. We used six different heaters: three kerosene heaters of different types, town and propane gas heaters, and an electric heater. Three ventilation conditions were introduced into each experiment: non-ventilation, fan-on ventilation with closed door and fan-off ventilation with half-opened door. The results obtained by heating under non-ventilation condition were as follows: The concentrations of NO2 and CO2 were comparatively high and the values obtained from all the heaters except the electric heater exceeded the 1-hr Environmental Quality Standards, Japan (EQS NO2: 0.04-0.06 ppm) and the Building Sanitation Management Standards, Japan (BSMS CO2: 1,000 ppm), respectively. The CO concentration emitted from reflection kerosene and town gas heaters slightly exceeded the BSMS (10 ppm). The concentrations of suspended particulate matter and polynuclear aromatic hydrocarbons showed an increasing tendency during the use of kerosene-fueled heaters. Under two ventilating conditions, NOx concentration decreased to less than a third in comparison with non-ventilating condition.

Air Pollutants↗
PubMed1995

Effects of ALDH2, CYP1A1, and CYP2E1 genetic polymorphisms and smoking and drinking habits on toluene metabolism in humans.

In this study, we evaluated the effects of ALDH2, CYP1A1, and CYP2E1 genetic polymorphisms and smoking and drinking habits on the toluene metabolism. The study subjects were 92 male workers who handle toluene in a printing factory, an electrical parts factory, and a painting workplace in Japan. Their exposure levels to toluene were monitored using the diffusion-type sampler. Benzyl alcohol concentrations in their blood and hippuric acid (HA) and creatinine concentrations in their urine at the end of a workshift were determined. The genotype of ALDH2 was classified into the homozygous genotype of a normal ALDH2 gene (NN), the homozygous genotype of an inactive ALDH2 gene (DD), and the heterozygous genotype of normal and inactive ALDH2 genes (ND). The genetic polymorphism of CYP1A1 and CYP2E1 were also determined by restriction fragment length polymorphism (RFLP). A strong correlation between the personal exposure level and the urinary HA concentration was observed. Regression lines were calculated after being divided by the five factors, i.e., ALDH2, CYP1A1, CYP2E1, smoking, and drinking. The HA formation from toluene was significantly (p < 0.001) different among the genotypes of ALDH2. The slopes of the regression lines decreased from NN to ND to DD in this order. The benzyl alcohol concentration in the blood of the DD group was significantly higher than that found in the NN and ND groups. This result demonstrates that ALDH2 polymorphism affects the oxidation of benzyl alcohol to benzoic acid. The toluene metabolism was also affected by CYP1A1 polymorphism. The slope for the Ile/Ile (the predominant homozygous allele) group was significantly lower than that for the Ile/Val (the heterozygous allele) and Val/Val (the rare homozygous allele) group after correction for creatinine. A drinking habit significantly (p < 0.05) reduced urinary HA concentration in the NN group. A smoking habit also significantly (p < 0.05) reduced urinary uncorrected HA concentration in both the NN and ND groups. In a multiple regression analysis, ALDH2 and the drinking habit were significantly (p < 0.01) associated with HA excretion after toluene exposure with and without correction for creatinine, and the corrected HA concentration was also significantly (p < 0.01) increased in the Ile/Val and Val/Val group of CYP1A1. The smoking habit reduced the corrected HA concentration (p < 0.05); however, the polymorphism in the 5'-flanking region of CYP2E1 did not affect HA appearance in urine.

Adult↗
PubMed1995

Interlaboratory quality control and status of n-hexane biological monitoring in Japan.

This paper reports the problem of interlaboratory quality control and the actual condition of biological monitoring of n-hexane among the seven major laboratories specializing in clinical chemistry tests, where more than 80% of the total urine specimens in Japan have been analyzed after the beginning of biological monitoring of n-hexane in 1989. First, transportation conditions of urine specimens and transportation effects on measurement results were studied. The seven major laboratories carried urine specimens at distances of more than 450 km from the University of Occupational and Environmental Health (UOEH) to the respective laboratories and had at least one transit terminal where specimens from various areas were collected and transferred to the analytical laboratories. All laboratories used cooler boxes with dry ice or ice bars and stored the specimens in freezers or refrigerators. Specimens arrived at the final destinations within 24 hours. The transportation from institutes for health examination to the laboratories did not affect the measurement results of 2,5-hexanedione (HD), a determinant of n-hexane biological monitoring. Interlaboratory cross-checks were performed among the seven major laboratories and four institutes for occupational health examination that have their own analytical laboratories. All of the laboratories analyzed HD by acid hydrolysis (pH < 1.0); interlaboratory differences were recognized at the first cross-check. After some laboratories intensified gas chromatography (GC) maintenance and changed to a new column, the interlaboratory variation lessened.(ABSTRACT TRUNCATED AT 250 WORDS)

Environmental Monitoring↗
PubMed1995

Biological monitoring of occupational exposure to methyl ethyl ketone in Japanese workers.

The relationship between occupational exposure to methyl ethyl ketone (MEK) and its concentration in urine and blood was studied in a group of 72 workers in a printing factory. Personal exposure monitoring was carried out with passive samplers during the workshifts. The time weighted average (TWA) concentration of MEK ranged from 1.3 to 223.7 ppm, with a mean concentration of 47.6 ppm. In addition to MEK, toluene, xylene, isopropyl alcohol, and ethyl acetate were detected as the main contaminants in all samples. At the end of the workshift, urine samples were collected to determine the urinary MEK, hippuric acid (HA), and creatinine, and blood samples were also collected at the same time for determination of MEK. The concentrations of urinary MEK ranged from 0.20 to 8.08 mg/L with a mean of 1.19 mg/L and significantly correlated with TWA concentrations of MEK in the air with a correlation coefficient of 0.889 for uncorrected urine samples. The concentration of MEK in the blood was also significantly correlated with the TWA concentration of MEK with a correlation coefficient of 0.820. From these relationships, MEK concentrations in urine and blood corresponding to the threshold limit value-TWA (200 ppm; ACGIH 1992) were calculated to be 5.1 mg/L and 3.8 mg/L as a biological exposure index (BEI), respectively. Although the BEI for urinary MEK obtained from the present study was higher than that of previous reports and ACGIH's recommendation (2.0 mg/L), the BEI agreed well with a previous study in Japan.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗