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Biomedical subjects

T Kawamoto

Publications and source records attributed to T Kawamoto.

At least 91 records · Page 5Linked to original sources

Cutting edge: combined treatment of TNF-alpha and IFN-gamma causes redistribution of junctional adhesion molecule in human endothelial cells.

Proinflammatory cytokines such as TNF-alpha and IFN-gamma induce cell adhesion molecules in endothelial cells and promote transmigration of leukocytes across endothelial cells. However, when those two were administered together, leukocyte transmigration paradoxically decreased. We cloned a human and bovine homologue of the junctional adhesion molecule (JAM), a novel molecule at the tight junction, and examined the effects of proinflammatory cytokines on JAM in HUVECs. The combined treatment of TNF-alpha plus IFN-gamma caused a disappearance of JAM from intercellular junctions. However, flow cytometry, cell ELISA, and subcellular fractionation analysis demonstrated that the amount of JAM was not reduced. This suggested that JAM changed its distribution in response to proinflammatory cytokines. This redistribution of JAM might be involved in a decrease in transendothelial migration of leukocytes at inflammatory sites.

Amino Acid Sequence↗

Enhancement of cell adhesion and spreading by a cartilage-specific noncollagenous protein, cartilage matrix protein (CMP/Matrilin-1), via integrin alpha1beta1.

Cartilage matrix protein (CMP; also known as matrilin-1), one of the major noncollagenous proteins in most cartilages, binds to aggrecan and type II collagen. We examined the effect of CMP on the adhesion of chondrocytes and fibroblasts using CMP-coated dishes. The CMP coating at 10-20 micrograms/ml enhanced the adhesion and spreading of rabbit growth plate, resting and articular chondrocytes, and fibroblasts and human epiphyseal chondrocytes and MRC5 fibroblasts. The effect of CMP on the spreading of chondrocytes was synergistically increased by native, but not heated, type II collagen (gelatin). The monoclonal antibody to integrin alpha1 or beta1 abolished CMP-induced cell adhesion and spreading, whereas the antibody to integrin alpha2, alpha3, alpha5, beta2, alpha5beta1, or alphaVbeta5 had little effect on cell adhesion or spreading. The antibody to integrin alpha1, but not to other subunits, coprecipitated 125I-CMP that was added to MRC5 cell lysates, indicating the association of CMP with the integrin alpha1 subunit. Unlabeled CMP competed for the binding to integrin alpha1 with 125I-CMP. These findings suggest that CMP is a potent adhesion factor for chondrocytes, particularly in the presence of type II collagen, and that integrin alpha1beta1 is involved in CMP-mediated cell adhesion and spreading. Since CMP is expressed almost exclusively in cartilage, this adhesion factor, unlike fibronectin or laminin, may play a special role in the development and remodeling of cartilage.

Animals↗

Noninvasive assessment of hemodynamic subsets in patients with acute myocardial infarction using digital color Doppler velocity profile integration and pulmonary venous flow analysis.

Four major hemodynamic subsets from cardiac index (CI) and mean pulmonary artery (PA) wedge pressure with a PA catheter usually reflect clinical status and prognosis of patients with acute myocardial infarction (AMI). Recently, a new color Doppler technique has been developed for automated cardiac output measurements (ACOM). Color Doppler echocardiography also provides noninvasive estimation of PA wedge pressure from pulmonary venous (PV) flow analysis. This study evaluates the value of ACOM and PV flow analysis by color Doppler echocardiography for the assessment of hemodynamic subsets in patients with AMI. We performed ACOM and PV flow analysis by color Doppler echocardiography in 55 patients with AMI who underwent hemodynamic assessment with a PA catheter. From both noninvasive and invasive methods, we classified hemodynamic subsets as follows: subset I: normal hemodynamics (CI >2.2 L/min/m2, PA wedge pressure < or =18 mm Hg); subset II: pulmonary congestion (CI >2.2 L/min/m2, PA wedge pressure >18 mm Hg); subset III: peripheral hypoperfusion (CI < or =2.2 L/min/m2, PA wedge pressure < or =18 mm Hg); and subset IV: pulmonary congestion and peripheral hypoperfusion (CI < or =2.2 L/min/m2, PA wedge pressure >18 mm Hg). Doppler assessment of hemodynamic subsets was possible in 50 of 55 patients (91%). CI from ACOM correlated well with that from the thermodilution method (r = 0.94) with close agreement. There was a good correlation between the systolic fraction (systolic velocity-time integral expressed as a fraction of the sum of systolic and diastolic velocity-time integrals) of PV flow and PA wedge pressure measured from cardiac catheterization (r = -0.83). When we determined the value of 45% in the systolic fraction as the cut-off point in predicting >18 mm Hg in PA wedge pressure, there was 90% (45 of 50 patients) agreement between noninvasive and invasive hemodynamic subsets. Thus, ACOM and PV flow analysis by color Doppler echocardiography is useful in the noninvasive assessment of hemodynamic subsets in patients with AMI.

Adult↗

The repressed nuclear receptor CAR responds to phenobarbital in activating the human CYP2B6 gene.

The endogenous CYP2B6 gene becomes phenobarbital (PB) inducible in androstenol-treated HepG2 cells either transiently or stably transfected with a nuclear receptor CAR expression vector. The PB induction mediated by CAR is regulated by a conserved 51-base pair element called PB-responsive enhancer module (PBREM) that has now been located between -1733 and -1683 bp in the gene's 5'-flanking region. An in vitro translated CAR acting as a retinoid X receptor alpha heterodimer binds directly to the two nuclear receptor sites NR1 and NR2 within PBREM. In a stably transfected HepG2 cell line, both PBREM and NR1 are activated by PB and PB-type compounds such as chlorinated pesticides, polychlorinated biphenyls and chlorpromazine. In addition to PBREM, CAR also transactivates the steroid/rifampicin-response element of the human CYP3A4 gene in HepG2 cells. Thus, activation of the repressed nuclear receptor CAR appears to be a versatile mediator that regulates PB induction of the CYP2B and other genes.

Aryl Hydrocarbon Hydroxylases↗

A study for the proper application of urinary naphthols, new biomarkers for airborne polycyclic aromatic hydrocarbons.

Urinary naphthols, 1- and 2-naphthol, recently have been suggested as route-specific biomarkers for exposure to airborne polycyclic aromatic hydrocarbons. For the proper application of urinary naphthols as biomarkers, we studied effects of lifestyle on urinary naphthols levels in 119 Japanese male workers. After improving the detection limit of urinary naphthols up to 0.27 microg/L by high-resolution capillary gas chromatography/mass spectrometry/selected ion monitoring, urinary naphthols were detectable in approximately 90% of the subjects. Among detectable samples, the geometrical mean (GM) of urinary 1-naphthol concentration was 5.13 microg/L (geometrical standard deviation, GSD, 4.90), while the GM of urinary 2-naphthol concentration was 3.16 microg/L (GSD, 5.61). We observed that urinary 1- and 2-naphthol level were three- and sevenfold higher, respectively, among smokers than among nonsmokers (p < 0.01). The ratios of urinary 2-naphthol to 1-naphthol were significantly higher among smokers than nonsmokers (p < 0.05). The number of cigarettes smoked and urinary cotinine levels were also positively related to the concentration of urinary naphthols (p < 0.01), while other lifestyle factors, i.e., age and consumption of alcohol, greasy or salty food, sweets, fruits, vegetables, meat, or fish, were not. We also studied whether genetic polymorphisms of enzymes, which were involved in naphthalene metabolism, affected urinary naphthols levels. The cytochrome P450 (CYP) 1A1 exon 7 genetic polymorphism was not related to urinary naphthol levels. Among smokers, the subjects with c1/c2 or c2/c2 type of CYP2E1, which was determined by CYP2E1 RsaI polymorphism in 5'-flaking region, showed higher concentrations of urinary 2-naphthol than the subjects with c1/c1 type regardless of creatinine-correction (p < 0.05) and the subjects with glutathione S-transferase (GST) M1 deficient type showed higher concentrations of both urinary 1- and 2-naphthol than those with GSTM1 normal type but only without creatinine-correction (p < 0.05). Thus, when urinary naphthols are used as biomarkers, smoking and the genetic polymorphisms of CYP2E1 and GSTM1 should be considered.

Adult↗

Noninvasive evaluation of pulmonary capillary wedge pressure in patients with acute myocardial infarction by deceleration time of pulmonary venous flow velocity in diastole.

OBJECTIVES: This study investigates the correlation between deceleration time of diastolic pulmonary venous flow (PV-DT) and of early filling mitral flow (LV-DT), and pulmonary capillary wedge pressure (PCWP) in patients with acute myocardial infarction (AMI). BACKGROUND: An earlier study suggests that Doppler-derived LV-DT provides an accurate means of estimating PCWP in postinfarction patients with left ventricular systolic dysfunction. Furthermore, recent studies have suggested that PCWP correlates better with PV-DT than with LV-DT. However, the value of PV-DT and LV-DT for assessment of PCWP in patients with AMI has not been evaluated. METHODS: In 141 consecutive patients with AMI, we measured PV-DT and LV-DT by Doppler echocardiography, and compared these variables with PCWP measured using a Swan-Ganz catheter. RESULTS: There was a weak negative correlation between the LV-DT and PCWP (r = -0.54). Although the sensitivity of < or =130 ms in LV-DT in predicting > or =18 mm Hg in PCWP was high (86%), its specificity was low (59%). On the other hand, a very close negative correlation was found between PV-DT and PCWP (r = -0.89). The sensitivity and specificity of < or =160 ms in PV-DT in predicting > or =18 mm Hg in PCWP were 97% and 96%, respectively. CONCLUSIONS: In patients with AMI, Doppler-derived PV-DT showed a stronger correlation with PCWP than LV-DT.

Adult↗

Efficient enzymatic synthesis of amide with (aminomethyl)trimethylsilane.

Hydrolase-catalyzed amide synthesis using a silicon-containing amine, (aminomethyl)trimethylsilane, as the substrate was studied. Six hydrolases (lipase OF 360, lipase Novo, lipase KLIP-001, lipoprotein lipase Type A, cholesterol esterase Type A, and cholesterol esterase III) were capable of forming the amide of (aminomethyl)trimethylsilane with octanoic acid in 2,2,4-trimethylpentane. Lipoprotein lipase Type A and cholesterol esterase Type A showed particularly the high levels of activity. From a comparative study of (aminomethyl)trimethylsilane and its carbon analog, 2,2-dimethylpropylamine, the former was found to be a better substrate for the hydrolases than the carbon analog. This difference is considered to arise from the specific properties of the silicon atom. (Aminomethyl)trimethylsilane exhibited a homotropic effect at concentration under 100 mM in amide synthesis by lipoprotein lipase Type A, while the carbon analog showed no such effect.

Journal Article↗

Treatment of gallbladder cancer by radical resection.

BACKGROUND: The use of radical resection for gallbladder cancer is controversial. This study evaluated results of resection for gallbladder cancer and analysed prognostic factors. METHODS: A retrospective review of 135 patients who underwent surgical resection for gallbladder cancer between 1976 and 1998 was performed. Of these, 123 patients underwent radical resection and the remaining 12 had palliative resection. The resections included 32 hepatopancreatoduodenectomies and 57 with adjuvant radiotherapy. Twelve prognostic factors were analysed. A subset of 96 patients with stage IV disease was analysed separately with respect to residual tumour level and adjuvant radiotherapy. RESULTS: Surgical resection was associated with a 5-year survival rate of 36 per cent, with a mean follow-up time of 870 days. Twenty-two patients have survived more than 5 years including three with stage IV disease. Overall operative morbidity and mortality rates were 13 and 4 per cent respectively. The 5-year survival rate decreased with disease stage: 100, 78, 69 and 11 per cent for stages I (n = 13), II (n = 19), III (n = 7) and IV (n = 96) respectively. Performance status, jaundice, histopathological type and grade, primary tumour, lymph node, distant metastasis, stage grouping, residual tumour level and adjuvant radiotherapy were significant prognostic factors. CONCLUSION: With careful patient selection, radical resection for gallbladder cancer improves the prognosis with acceptable operative mortality and morbidity rates, even for stage IV disease, provided that complete gross tumour resection is combined with radiotherapy.

Adult↗

NAT2 gene polymorphism as a possible marker for susceptibility to bladder cancer in Japanese.

BACKGROUND: N-acetyltransferase (NAT) is known to metabolize the carcinogen arylamine. The polymorphism of the NAT2 gene is an important determinant of individual susceptibility to bladder cancer. There are significant interethnic differences in NAT2 allele frequencies. The relationship between NAT2 genotypes and bladder cancer in a Japanese population was investigated. METHODS: A case control study on 85 bladder cancer patients and 146 control subjects was conducted. NAT2 alleles were differentiated by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methods using originally created PCR primers and genomic DNA extracted from peripheral white blood cells. The NAT2 genotypes were determined by the combination of three known NAT2 mutant type alleles (M1, M2, M3) and the wild type allele. RESULTS: NAT2 slow genotypes were associated with bladder cancer risk (odds ratio adjusted for age and gender, 4.23; 95% confidence interval [CI], 1.76-10.81). Among those with NAT2 slow genotypes/smoker, there was a significantly increased risk of 7.80 (95% CI, 1.66-57.87) when the NAT2 rapid genotypes/non-smoker were considered the reference group. This suggested a possible interaction between NAT2 slow genotypes/smoking status and bladder cancer risk. It was also shown that bladder cancer patients with NAT2 slow genotypes were more likely to have a high grade tumor (G3) or an advanced stage tumor (pT2-pT4) [corrected]. However, no association between NAT2 genotypes and the survival rate of invasive bladder cancer patients was recognized. CONCLUSION: It was demonstrated that the NAT2 slow acetylation genotype is an important genetic determinant for bladder cancer in a Japanese population.

Acetylation↗

Phenobarbital-responsive nuclear translocation of the receptor CAR in induction of the CYP2B gene.

The constitutively active receptor (CAR) transactivates a distal enhancer called the phenobarbital (PB)-responsive enhancer module (PBREM) found in PB-inducible CYP2B genes. CAR dramatically increases its binding to PBREM in livers of PB-treated mice. We have investigated the cellular mechanism of PB-induced increase of CAR binding. Western blot analyses of mouse livers revealed an extensive nuclear accumulation of CAR following PB treatment. Nuclear contents of CAR perfectly correlate with an increase of CAR binding to PBREM. PB-elicited nuclear accumulation of CAR appears to be a general step regulating the induction of CYP2B genes, since treatments with other PB-type inducers result in the same nuclear accumulation of CAR. Both immunoprecipitation and immunohistochemistry studies show cytoplasmic localization of CAR in the livers of nontreated mice, indicating that CAR translocates into nuclei following PB treatment. Nuclear translocation of CAR also occurs in mouse primary hepatocytes but not in hepatocytes treated with the protein phosphatase inhibitor okadaic acid. Thus, the CAR-mediated transactivation of PBREM in vivo becomes PB responsive through an okadaic acid-sensitive nuclear translocation process.

Animals↗

Retinol-binding protein is produced by rabbit chondrocytes and responds to parathyroid hormone (PTH)/PTH-related peptide-cyclic adenosine monophosphate pathway.

PTH and dibutyryl cAMP [(Bu)2cAMP] induced the expression of a 19-kDa protein in the conditioned media of rabbit growth plate chondrocyte cultures. The 19-kDa protein was identified as plasma retinol-binding protein (RBP) by aminoterminal sequence analysis and immunoblot analysis with an anti-RBP monoclonal antibody. Northern blot analysis showed that PTH, PTH-related peptide (PTHrP), and (Bu)2cAMP increased the RBP messenger RNA (mRNA) level in chondrocyte cultures. Further, both PTH and (Bu)2cAMP markedly induced the expression of RBP mRNA by about 10-fold at 3 h and by about 40-fold at 24 h, indicating a pretranslational regulation. The level of the mRNA expression induced by PTH, PTHrP, and (Bu)2cAMP was as high as that by retinoic acid (RA), known as a potent inducer of RBP in hepatoma cells. RBP mRNA was also detected in cartilage tissues at higher levels than in the other tissues examined except liver. Both RBP and PTH/PTHrP inhibited the dedifferentiative activity of RA on growth plate chondrocytes when added to the culture medium. These results demonstrate that chondrocytes synthesize and secrete RBP in vivo and in vitro and suggest that PTH/PTHrP modulates the effect of RA by means of RBP production in chondrocytes.

Amino Acid Sequence↗

[A study of air pollution in the smoking hall].

We investigated the air pollution in the student smoking hall from February 1st in the winter season, and during 8 days in the middle of April in the spring season. The student smoking hall was in an open, draught location. Moreover, the concentration of pollutants were measured in three time periods: break, lecture and lunch times. The pollutants measured were nitrogen monoxide (NO), nitrogen dioxide (NO2), carbon monoxide (CO), carbon dioxide (CO2), suspended particulate matter (SPM) and polynuclear aromatic hydrocarbon (PAH). The concentrations of pollutants measured during the break times were of a relatively higher level than those during the lecture and lunch times. However, the concentration of pollutants were not influenced by ventilation operation in the smoking hall, which is not a closed place. SPM and CO2 concentrations during the break time were instantaneously investigated above Building Sanitation Standards Management, Japan (SPM: 0.15 mg/m3, CO2: 1,000 ppm). Especially, the SPM concentration was recognized to be strongly influenced by tobacco smoke.

Air Pollution, Indoor↗

[Remaining solvents in dry cleaned over clothes].

We examined remaining solvents in dry cleaned trousers to estimate the magnitude of environmental pollution. A cleaning solvent of petroleum hydrocarbon was analyzed by means of capillary column mass spectrum gas chromatography. Principal ingredients were identified to be nonane, decane and undecane. The same main components were detected in dry cleaned trousers. Total amounts of evaporated vapor from a pair of trousers (480 g) in 5 days after dry cleaning were nonane (0.73 mg), decane (1.53 mg) and undecane (1.09 mg). The levels on the fifth day were 5%(nonane), 18%(decane) and 32%(undecane) of the first day's concentration, respectively. The half times of the remaining solvents were 1.0 day (nonane), 1.7 days (decane) and 2.7 days (undecane), respectively.

Clothing↗

Primary central nervous system T-cell lymphoma. Case report.

A 46-year-old male presented with a rare primary non-Hodgkin's lymphoma of the central nervous system of T-cell lineage, localized primarily in the right parietal region. There was no evidence of acquired immunodeficiency syndrome. Biopsy of the tumor allowed immunohistochemical confirmation of the diagnosis. Irradiation and chemotherapy were given, and the patient has remained well for 24 months. The clinical manifestations, management, and outcome of T-cell lymphoma are very similar to those of B-cell lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗

[Evaluation of mitral valve lesions in patients with infective endocarditis by three-dimensional echocardiography].

Recognition of the involved lesions is extremely important in mitral valve repair for infective endocarditis. Transesophageal echocardiography (TEE) is more sensitive for the detection of lesions than transthoracic echocardiography, but localization of the lesions is sometimes difficult by TEE. Three-dimensional (3D) TEE provides images of the mitral valve similar to the view from the left atrium. This study evaluated the value of 3D echocardiography for the diagnosis of involved lesions in 12 patients who underwent surgery for mitral regurgitation due to infective endocarditis. The location of the lesion in the mitral valve was classified as the medial, central and lateral portions of the anterior leaflet, and the medial, middle and lateral scallops of the posterior leaflet, respectively. In all patients, the involved sites were confirmed at operation. The sensitivities of 3D TEE for detecting the lesions at the medial, central and lateral portions of the anterior leaflet, and the medial, middle and lateral scallops of the posterior leaflet were 100%, 78% and 67%, and 100%, 100% and 100%, respectively. The specificities were 90%, 100% and 78%, and 100%, 100% and 100%, respectively. The lesions diagnosed by 3D TEE coincided with lesions confirmed at operation in 23 (92%) of 25 lesions. 3D TEE is useful for the assessment of the involved lesion of the mitral valve in patients with infective endocarditis.

Echocardiography, Three-Dimensional↗

[Effects of imaging parameters on automated cardiac flow measurement using color Doppler echocardiography].

The color Doppler echocardiographic technique has been developed for automated cardiac flow measurement (ACM). This study evaluated the effect of imaging parameters on stroke volume measurement. Cardiac output derived from the ACM method was compared with that obtained from pulsed wave Doppler in 36 patients (26 men and 10 women, mean age 54 +/- 8 years) in whom clear two-dimensional and color Doppler images of the left ventricular outflow tract were obtained. The effects of frame rate, color gain and moving target indicator (MTI) filter on cardiac output were evaluated in 13 patients (8 men and 5 women, mean age 49 +/- 6 years). Using ACM at a frame rate of 30 Hz, optimal color gain setting and high-frequency MTI filter (cutoff frequency: 915 Hz), there was an excellent correlation in cardiac output between the ACM and pulsed wave Doppler methods (stroke volume: r = 0.91, SEE = 0.32 l/min). Using ACM at a frame rate of 30, 22 and 15 Hz, the differences in stroke volume were 4.4%, 5.2% and 8.6%, respectively. When color gain was reduced, left ventricular stroke volume reduction was 12.1% (-2 dB), 18.9% (-4 dB). In contrast, there was no significant change in stroke volume measurement when color gain was increased. There was a significant decrease in stroke volume using the low-frequency MTI filter [cutoff frequency: 467 Hz (-35.6%)] and medium-frequency MTI filter [cutoff frequency: 703 Hz (-13.4%)]. Color Doppler imaging parameters are extremely important for automated assessment of cardiac output.

Automation↗