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T Kawamoto

Publications and source records attributed to T Kawamoto.

At least 73 records · Page 4Linked to original sources
PubMed2000

Synthesis and antitumor activities of novel 5-deazaflavin-sialic acid conjugate molecules.

6-Nitro-5-deazaflavin derivatives bearing O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha- and beta-D-galacto-non-2-ulopyranosylonate)alkyl group (sialosylalkyl group) at N(3) or N(10) and 8-amino-5-deazaflavin substituted with the sialosylalkyl group at the amino group were synthesized and their physicochemical properties as well as antitumor effects on KB and L1210 cells have been investigated. The configurations of the glycosides were determined by 1H NMR and rate of hydrolysis of the glycosidic bond. It has been found that these conjugate molecules show significant antitumor activities. Combination of an 8-amino-5-deazaflavin with the sialosylalkyl group have been found to give rise to significant increase in antitumor activities of the compound. Antitumor effects of 6-nitro-5-deazaflavin-sialic acid conjugate molecules were similar or rather weak in comparison with those of the 6-nitro-5-deazaflavin derivatives without sialosylalkyl group.

Animals↗
PubMed2000

Radical resection of hilar bile duct carcinoma and predictors of survival.

BACKGROUND: Patients with carcinoma of the main hepatic duct have a poor prognosis. This study attempted to identify clinicopathological predictors of survival after resection. METHODS: A retrospective review was performed of 114 patients who presented with hepatic ductal carcinoma between 1976 and 1998. Of the 114 patients, 98 had a radical resection, three underwent palliative resection and 13 were not treated surgically. Forty-six patients with stage IVA disease had microscopic tumour residue after resection. Of these, 28 patients were treated with radiotherapy and the remaining 18 had resection alone. RESULTS: The overall operative morbidity and mortality rates were 14 and 4 per cent respectively. The overall 5-year survival rate after resection was 28 per cent. Nineteen patients survived for more than 5 years, including ten with stage IVA disease. The main prognostic factors were performance status; jaundice; tumour location; gross appearance; histological grade; T, N and M categories in tumour node metastasis (TNM) classification; TNM stage; and residual tumour. Adjuvant radiotherapy, tumour extension into the hepatic ducts, histological grade, N and residual tumour were independent predictive factors by multivariate Cox analysis. CONCLUSION: This study suggests that radical resection provides the best survival rate for patients with hilar bile duct carcinoma. For patients with stage IVA disease, following complete gross resection radiotherapy improved treatment outcome.

Adult↗
PubMed2000

Asymptomatic schwannoma of the oculomotor nerve: case report.

Intracranial oculomotor schwannoma without neurofibromatosis is rare and is usually symptomatic. Only one case of asymptomatic oculomotor schwannoma has been previously reported. We present a case of intracranial oculomotor schwannoma which caused no signs or symptoms. Microsurgical resection of this tumour resulted in oculomotor palsy. We reviewed 7 reported cases and the findings indicated that radical removal of the tumour invariably caused or worsened the oculomotor palsy. The reason why the tumour caused no symptoms in this case was unclear. However, improvements in diagnostic methods such as magnetic resonance imaging (MRI) may increase the detection of such asymptomatic cases. Indications for surgical treatment should be established.

Aged↗
PubMed2000

Bilateral medial medullary infarction.

We present a case of bilateral medial medullary infarction demonstrated by magnetic resonance imaging (MRI) and review 12 previously reported cases. We classify these 13 cases (including the present case) into two groups according to the extent of the ischemic region: type 1, the ischemic lesion developed from the medullary pyramid to the medial longitudinal fasciculus; type 2, the lesion was confined to the medullary pyramid.A 71 year old man presented with slight disturbance of consciousness, dysarthria, disturbance of leftward gaze, no gag reflex and tetraparesis. He developed nearly complete horizontal ophthalmoplegia. MRI revealed upper medial medullary infarction bilaterally that extended to the pontomedullary junction. We propose that the prognosis of type 2 bilateral medial medullary infarction is better than that of type 1. Furthermore, the prognosis of bilateral medial medullary infarction itself may be better than previously indicated.

Aged↗
PubMed2000

Enteral vitamin B12 supplements reverse postgastrectomy B12 deficiency.

OBJECTIVE: To examine the development of chemical and clinical vitamin B12 deficiency after total gastrectomy, and to evaluate the efficacy of supplemental oral B12 administration. SUMMARY BACKGROUND DATA: Postgastrectomy anemia is due to deficiencies of iron and vitamin B12, and parenteral B12 administration is the only appropriate treatment. However, no guidelines exist for the prophylactic use of B12 in patients who undergo total gastrectomy, the clinical presentation of B12 deficiency in this context has not been defined, and the question of whether oral B12 administration can be used to prevent and treat B12 deficiency has not been examined. METHODS: Serum B12 concentrations were measured in 31 patients who had undergone total gastrectomy. Symptoms related to B12 deficiency were surveyed in detail. Serum B12 concentrations were measured every 6 months after total gastrectomy in 10 patients. Thirty one patients received supplemental B12: 18 patients orally and 13 by intramuscular injection. RESULTS: The B12 concentration dropped below the lower limit of normal (200 pg/mL) for the first time in two patients at 1 year, in four patients at 2 years, in three patients at 3 years, and in one patient at 4 years. Seventy-eight percent of patients reported some symptoms related to B12 deficiency. The serum B12 concentration in patients who received supplemental B12 orally increased rapidly and all symptoms resolved with oral therapy alone. CONCLUSIONS: B12 deficiency can develop as early as 1 year after total gastrectomy and causes symptoms. Because enteral B12 treatment increases the serum B12 concentration and leads to rapid resolution of symptoms, it should be prescribed routinely to patients undergoing total gastrectomy.

Administration, Oral↗
PubMed2000

Relationship between NAT1 genotype and phenotype in a Japanese population.

NAT1, which biotransforms many carcinogens, is genetically polymorphic. This polymorphism has been postulated as a mechanism for susceptibility differences in cancer, possibly due to NAT1 activity differences. However, the relationship between NAT1 genotype and phenotype is not clear. In our study of 110 Japanese, the frequency of the NAT1*10 allele (0.53, 95% confidence interval 0.46-0.59) was higher than others have observed in Caucasians (0.16). From genotype frequency studies, 26.4% of the subjects belonged to the NAT1*10/*10 genotype, 53.6% to the NAT1*4/*10 genotype and 20% to the NAT1*4/*4 genotype. Neither NAT1*3 nor NAT1*11 genotype was seen in these subjects. In female subjects, we found higher NAT1 activity in NAT1*4/*10 subjects than in NAT1*4/*4 subjects (n = 49; 2.63 versus 2.16 nmol/min/mg protein). NAT1 activity-difference between NAT1*4/*10 and NAT1*10/*10 was not statistically significant. Thus, not only the presence of NAT1*10 allele, but also other factors are suspected of increasing NAT1 activities. After full sequencing of 10 subjects, five individuals having the highest activities and five individuals having the lowest activities, we found NAT1*18A and NAT1*18B to be in the high activity group and the low activity group, respectively. The genotypes containing these variants were heterozygous, i.e. NAT1*4/*18A and NAT1*4/*18B. Due to rare frequencies of these variants, they cannot be considered as other effective, genetic factors on NAT1 activity. Age and tobacco smoking did not affect the relationship between NAT1 genotype and phenotype.

4-Aminobenzoic Acid↗
PubMed2000

Estrogen activation of the nuclear orphan receptor CAR (constitutive active receptor) in induction of the mouse Cyp2b10 gene.

The nuclear orphan receptor CAR (constitutively active receptor or constitutive androstane receptor) can be activated in response to xenochemical exposure, such as activation by phenobarbital of a response element called NR1 found in the CYP2B gene. Here various steroids were screened for potential endogenous chemicals that may activate CAR, using the NR1 enhancer and Cyp2b10 induction in transfected HepG2 cell and/or in mouse primary hepatocytes as the experimental criteria. 17beta-Estradiol and estrone activated NR1, whereas estriol, estetrol, estradiol sulfate, and the synthetic estrogen diethylstilbestrol did not. On the other hand, progesterone and androgens repressed NR1 activity in HepG2 cells, and the repressed NR1 activity was fully restored by estradiol. Moreover, estrogen treatment elicited nuclear accumulation of CAR in the mouse livers, as well as primary hepatocytes, and induced the endogenous Cyp2b10 gene. Ovariectomy did not affect either the basal or induced level of CAR in the nucleus of the female livers, while castration slightly increased the basal and greatly increased the induced levels in the liver nucleus of male mice. Thus, endogenous estrogen appears not to regulate CAR in female mice, whereas endogenous androgen may be the repressive factor in male mice. Estrogen at pharmacological levels is an effective activator of CAR in both female and male mice, suggesting a biological and/or toxicological role of this receptor in estrogen metabolism. In addition to mouse CAR, estrogens activated rat CAR, whereas human CAR did not respond well to the estrogens under the experimental conditions.

Androgens↗
PubMed2000

Cyclooxygenase expression in the gallbladder.

The COX expressions were evaluated separately in the epithelium and in the stroma of gallbladder cancer, chronic cholecystitis, xanthogranulomatous cholecystitis (XGC) and the normal gallbladder. In normal gallbladder COX-2 expression rate was significantly higher in the epithelium than in the stroma. The COX-2 expression rate in the epithelium of non-cancerous adjacent epithelium to cancerous lesion was significantly lower than those not only of cancer, but also chronic cholecystitis, XGC and normal gallbladder. In stroma, the COX-2 expression rate in cancer, chronic cholecystitis and XGC were significantly higher than that of the normal gallbladder. The rate in non-cancerous adjacent stroma to cancer is significantly lower than that of cancer and XGC. However, the difference of rate between of normal and of chronic cholecystitis was not significant. The COX-2 expression rates were significantly higher in both the epithelium and the stroma in the well and moderately differentiated cancer group than in the poorly and undifferentiated cancer group. Our results suggest that COX-2 expression in the gallbladder may be regulated by various factors and not directly related to carcinogenesis. The significance of its repression in the non-cancerous adjacent tissue to cancer lesion should be re-evaluated.

Cholecystitis↗
PubMed2000

Low-molecular-weight heparin as a multipurpose anticoagulant for laboratory testing.

The availability of low-molecular-weight heparin (LMWH) for use as an anti-coagulant for laboratory testing was studied. Hematology and chemistry tests were performed with an automated hematology analyzer and an automated chemistry analyzer, respectively. The results of hematology tests of LMWH-treated blood were similar to those obtained for blood treated with ethylenediaminetetraacetic acid (EDTA)-2K, except for platelet count. The platelet count of LMWH-treated blood was lower than that of EDTA-treated blood, and the decrease in platelet count in the former was due to platelet aggregation. Prothrombin time tests could be performed with plasma prepared from LMWH-treated blood, although with such blood the prothrombin time was prolonged. Chemistry tests could be performed for all 18 parameters. These results suggest that LMWH is a candidate for use for hematology testing (with the exception of platelet count), coagulation testing, and chemistry tests.

Anticoagulants↗
PubMed1999

Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and oral cavity cancer.

Both genetic and environmental factors are involved in the development of cancer. Oral cavity cancer has been reported to be epidemiologically associated with tobacco and alcohol consumption. We examined genetic polymorphisms of the glutathione-S-transferase (GST) M1/T1, cytochrome P-450 (CYP) 1A1/2E1 and aldehyde dehydrogenase 2 (ALDH2) genes in 92 Japanese patients with oral cavity cancer and 147 unrelated non-cancer Japanese controls. There was a significant association between cigarette smoking and cancer risk but no significant association between alcohol consumption and cancer risk. The frequency of the GSTM1 null genotype was significantly higher in cancers (58.7%) compared with controls (46. 3%). However, there were no significant differences between controls and patients with oral cavity cancer in the polymorphisms of the GSTT1, CYP1A1, CYP2E1 and ALDH2 genes. From statistical evaluation on various combinations of genotypes, we did not observe any gene combinations associated with cancer risk. There were also no genetic polymorphisms associated with increased risk of oral cavity cancer among smokers and drinkers. These results imply that the GSTM1 null genotype has a weak correlation, but another 4 genetic polymorphisms are unlikely to be associated, with oral cavity cancer among Japanese.

Adult↗
PubMed1999

Assay of 2-naphthol in human urine by high-performance liquid chromatography.

This paper describes a novel liquid chromatographic method for the quantitation of 2-naphthol in human urine. Urine samples were extracted after enzymatic hydrolysis of glucuronides and sulfates; 2-naphthol was then separated using reversed-phase high-performance liquid chromatography. The corresponding detection limits were 0.04 ng/ml for the standard sample in acetonitrile and 0.13 ng/ml for urine samples. The level of urinary 2-naphthol in 100 Korean shipyard workers was analyzed using this new method. The level ranged from 0.21 ng/ml (0.26 micromol/mol creatinine) to 34.19 ng/ml (59.11 micromol/mol creatinine), and the mean+/-standard deviation was 5.08 ng/ml (6.60 micromol/mol creatinine)+/-5.75 ng/ml (9.22 micromol/mol creatinine). The mean+/-standard deviation of urinary 2-naphthol level of smokers, 7.03 ng/ml (8.49 micromol/mol creatinine)+/-6.16 ng/ml (10.23 micromol/mol creatinine), was significantly higher than that of non-smokers, 2.49 ng/ml (4.10 micromol/mol creatinine)+/-3.92 ng/ml (7.03 micromol/mol creatinine).

Acetonitriles↗
PubMed1999

Prediction of progression or regression of type A aortic intramural hematoma by computed tomography.

BACKGROUND: It has been reported that early surgery should be required for patients with type A aortic intramural hematoma (IMH) because it tends to develop classic aortic dissection or rupture. However, the anatomic features of type A IMH that develops dissection or rupture are unknown. The purpose of this study was to investigate the predictors of progression or regression of type A IMH by computed tomography (CT). METHODS AND RESULTS: Twenty-two consecutive patients with type A IMH were studied by serial CT images. Aortic diameter and aortic wall thickness of the ascending aorta were estimated in CT images at 3 levels on admission and at follow-up (mean 37 days). We defined patients who showed increased maximum aortic wall thickness in the follow-up CT (n=9) or died of rupture (n=1) as the progression group (n=10). The other 12 patients, who all showed decreased maximum wall thickness, were categorized as the regression group. In the progression group, the maximum aortic diameter in the initial CT was significantly greater than that in the regression group (55+/-6 vs 47+/-3 mm, P=0.001). A Cox regression analysis revealed that the maximum aortic diameter was the strongest predictor for progression of type A IMH. We considered the optimal cutoff value to be 50 mm for the maximum aortic diameter to predict progression (positive predictive value 83%, negative predictive value 100%). CONCLUSIONS: Maximum aortic diameter estimated by the initial CT images is predictive for progression of type A IMH.

Aged↗
PubMed1999

Membrane-bound transferrin-like protein (MTf): structure, evolution and selective expression during chondrogenic differentiation of mouse embryonic cells.

Mouse membrane-bound transferrin-like protein (MTf) cDNA was cloned to examine its expression during chondrogenic differentiation in the mouse embryonic cell line ATDC5, and to analyze the phylogenetic relationships among the MTfs of four animal species and 23 other transferrin members. Phylogenetic analysis indicated that the MTf gene diverged from the common ancestor gene earlier than the genes of the other transferrins such as serum transferrin, lactoferrin and ovotransferrin, and that the divergence occurred after the divergence of vertebrates and invertebrates. MTf, as well as the other transferrins, consists of two repeated domains. The similarity between the N-terminal and the C-terminal domains of MTf is much higher than that of the other transferrins, although the five amino acid residues required for iron binding were not conserved in the C-terminal domain of MTf in contrast to the conservation of these residues in both domains of the other transferrins. Among various adult mouse tissues, MTf mRNA was expressed at the highest level in cartilage and at a moderate level in the testis. MTf mRNA was expressed only at very low levels in the brain, spleen, thymus, muscle, lung, skin and intestine, and hardly detected in the heart, kidney, stomach and liver. In cultures of the mouse ATDC5 cell line, MTf is developmentally expressed in parallel with the expression of type II collagen and aggrecan, in the pattern commensurate with the onset of chondrogenesis to form cartilage nodules. The structural characteristics and the expression pattern suggest that during development and in adult tissues, MTf has some functions that are different from those of other transferrins.

Amino Acid Sequence↗
PubMed1999

The significance of the homozygous CYP2A6 deletion on nicotine metabolism: a new genotyping method of CYP2A6 using a single PCR-RFLP.

A convenient and specific CYP2A6 genotyping method was developed in this study. This method consisting of a single PCR-RFLP is capable of resolving the genotype into either CYP2A6*1 (wild type), CYP2A6*2, or CYP2A6*3. Among 252 Japanese persons genotyped, 241 were genotyped as the wild type, 1 as an unknown variant, and none as either CYP2A6*2 or CYP2A6*3. A homozygous deletion was found in the 10 remaining subjects. To clarify the metabolic significance of this deletion in the whole human body, urinary cotinine, the principal metabolite of nicotine, was analyzed subsequent to smoking. Cumulated urinary cotinine excretion in the homozygously CYP2A6-deleted individuals was about one-seventh compared to the control group (wild type). This study provides a firm experimental basis for correlating genotypic characterization of CYP2A6 with phenotypic expression of nicotine metabolism.

Alleles↗
PubMed1999

RGD-CAP ((beta)ig-h3) enhances the spreading of chondrocytes and fibroblasts via integrin alpha(1)beta(1).

In previous studies, RGD-CAP (collagen-associated protein containing the RGD sequence) isolated from a collagen fiber-rich fraction of pig cartilage was found to be orthologous to human (beta)ig-h3, which is synthesized by lung adenocarcinoma cells in response to transforming growth factor-beta. In the present study, we examined the effect of recombinant chick RGD-CAP on the spreading of chondrocytes and fibroblasts using RGD-CAP-coated dishes. When rabbit articular chondrocytes, chick embryonic sternal chondrocytes, rabbit peritoneal fibroblasts or human MRC5 fibroblasts were seeded on plastic dishes coated with RGD-CAP, cell spreading was enhanced compared with that on control dishes (bovine serum albumin- or beta-galactosidase-coated dishes). The effect of RGD-CAP on the cell spreading required divalent cations (Mg(2+) or Mn(2+)), and was reduced by EDTA. Monoclonal antibodies (mAbs) to the human integrin alpha(1) or beta(1) subunit, but not to the alpha(2), alpha(3), alpha(5) or beta(2) subunits, suppressed the RGD-CAP-induced spreading of human MRC5 fibroblasts. In a parallel experiment, the mAb to the alpha(5) subunit, but not the mAb to the alpha(1) subunit, suppressed fibronectin-induced spreading of these cells. These findings suggest that RGD-CAP is a novel ligand for integrin alpha(1)beta(1) that dose not bind to the RGD motif. Accordingly, an RGD-CAP fragment, which carries a deletion in the C-terminal region containing the RGD motif, was still capable of stimulating cell spreading.

Animals↗
PubMed1999

Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine under anaerobic conditions by reductively activated nitro 5-deazaflavin derivatives.

Electrolytically reduced 6- and 8-nitro-5-deazaflavin derivatives have been found to interact to react specifically with guanine base by means of cyclic voltammetry. Electrolytic reductions of 6- and 8-nitro-5-deazaflavin derivatives in the presence of the 2'-deoxyguanosine under anaerobic conditions resulted in prominent formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Can coronary blood flow velocity pattern after primary percutaneous transluminal coronary angioplasty [correction of angiography] predict recovery of regional left ventricular function in patients with acute myocardial infarction?

BACKGROUND: In the era of primary percutaneous transluminal coronary angioplasty (PTCA), it is important to judge whether myocardium within acute ischemic injury is viable. This study sought to investigate parameters derived from the coronary blood flow velocity spectrum immediately after primary PTCA in patients with acute myocardial infarction and to elucidate the clinical value of coronary blood flow measurement in predicting myocardial viability. METHODS AND RESULTS: Using a Doppler guidewire, we measured coronary blood flow velocity after successful completion of primary PTCA in 23 consecutive patients with acute anterior myocardial infarction. Regional wall motion was analyzed to estimate anterior wall motion score index (A-WMSI) by echocardiography before PTCA and 1 month after the onset of symptoms. Average systolic peak velocity (ASV) and deceleration time of diastolic flow velocity (DDT) significantly correlated to 1-month A-WMSI (r=-0.54, P=0.007 and r=-0.62, P=0.002, respectively), and optimal cutoff values to predict viable myocardium (defined as 1-month A-WMSI </=2.0) were 6.5 cm/s for ASV and 600 ms for DDT (sensitivity=0.79, specificity=0.89 and sensitivity=0.86, specificity=0.89, respectively). ASV and DDT also correlated weakly to the change in A-WMSI (r=0.46, P=0.03 and r=0.49, P=0.02, respectively). CONCLUSIONS: Low ASV and rapid DDT of coronary blood flow spectrum immediately after primary PTCA reflects a greater degree of microvascular damage in the risk area. Analysis of coronary blood flow spectrum immediately after primary PTCA by use of a Doppler guidewire is useful in predicting recovery of regional left ventricular function.

Aged↗