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Biomedical subjects

T Katoh

Publications and source records attributed to T Katoh.

At least 37 records · Page 2Linked to original sources

Significance of vitamin D receptor gene polymorphism for risk and disease severity of prostate cancer and benign prostatic hyperplasia in Japanese.

OBJECTIVE: Recent studies have demonstrated an association between vitamin D receptor (VDR) genotype and prostate cancer. Currently, there is a scarcity of data regarding the association of VDR genotype with benign prostatic hyperplasia (BPH). The purpose of this study was to investigate the TaqI VDR polymorphism in Japanese prostate cancer patients, Japanese BPH patients and Japanese controls in order to determine if an association exists between VDR genotype and the risk of developing prostate cancer and BPH as well as disease severity. METHODS: 110 prostate cancer patients, 83 BPH patients and 90 male age-matched controls were genotyped for a previously described TaqI restriction fragment length polymorphism at codon 352 in exon 9 of the VDR gene. Products were digested into T allele or t allele according to the absence or presence of a TaqI restriction site with individuals being classified as TT, Tt or tt. RESULTS: The frequency of the genotype tt was higher in the control group (6.7%) compared to patients with prostate cancer (1.8%) and BPH (3.6%) but this was not statistically significant. However, the frequency of the genotype TT was significantly higher among prostate cancer patients with locally advanced or metastatic disease (T3/ T4/N1/M1) compared to controls (p = 0.001). In addition, the genotype TT was significantly higher among prostate cancer patients with a high Gleason grade of tumor (grade 5) compared to controls (p = 0.0001). In addition, the genotype TT was statistically higher in BPH patients with high prostate volume (volume >50 cm(3)) compared to controls (p = 0.001). CONCLUSION: These data demonstrate that VDR genotype plays an important role in determining the risk of more advanced and aggressive prostate cancer as well as prostatic enlargement in Japanese men.

Aged↗

[Concomitant lobectomy for lung cancer under intraaortic balloon pumping and coronary bypass grafting].

A 71-year-old man was admitted because of an abnormal shadow on the chest X-ray film. Chest computed tomography (CT) revealed a tumor in the right upper lobe. The diagnosis of lung cancer was made by transbronchial lung biopsy. He had suffered an infarction of the inferior myocardial wall at the age of 55 years. Preoperative coronary angiography revealed total occlusion of segment 1, 75% stenosis of segments 5 and 6, and 90% stenosis of segment 13. Since these coronary lesions could cause perioperative and postoperative myocardial infarction, the patient was scheduled to undergo surgery of both the heart and lung in a one-stage operation. Under intraaortic balloon pumping (IABP), we performed a right upper lobectomy of the lung, and coronary artery bypass grafting with cardiopulmonary bypass through median sternotomy. During the lobectomy and first postoperative day, a stable circulation was achieved with IABP. The postoperative course was uneventful. At present, that is 33 months after the operation, the patient presents no sighs of recurrence of lung cancer and has not suffered any anginal attack during follow-up. Lung cancer and coronary artery disease can be treated simultaneously by this procedure.

Aged↗

[Contralateral pneumothorax after pneumonectomy for bronchogenic carcinoma; report of a case].

A case of contralateral pneumothorax after pneumonectomy was reported. Intrathoracic drainage was performed and pneumothorax was healed. Recurrent pneumothorax was occurred in this patient and intrathoracic drainage was performed again and pneumothorax was healed. We suspected that bulla was the cause of pneumothorax and thought that contralateral pneumothorax after pneumonectomy must be carefully follow-up.

Aged↗

Endomorphin-1 improves scopolamine-induced impairment of short-term memory via mu1-opioid receptor in mice.

The effects of intracerebroventricular injection of endomorphin-1 and 2, endogenous mu-opioid receptor agonists, on the scopolamine-induced impairment of spontaneous alternation performance associated with short-term memory were investigated in mice. Endomorphin-1 (0.03 microg) inhibited scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance without affecting total arm entries, while endomorphin-2 (0.01-10 microg) failed to significantly influence the scopolamine (1 mg/kg)-induced impairment. Endomorphin-1 (0.03 microg) itself had no marked effects on spontaneous alternation performance in intact mice. Although beta-funaltrexamine (5 microg), a mu-opioid receptor antagonist, did not significantly affect the inhibitory effects of endomorphin-1 (0.03 microg) on the scopolamine (1 mg/kg)-induced impairment, naloxonazine (35 mg/kg), a mu1-opioid receptor antagonist, significantly reversed the inhibitory effects of endomorphin-1 (0.03 microg) on the impairment. Naloxonazine (35 mg/kg) unlike beta-funaltrexamine (5 microg) did not significantly influence the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance. These results suggest that endomorphin-1 improves the disturbance of short-term memory resulting from cholinergic dysfunction through the mediation of mu1-opioid receptors.

Analgesics, Opioid↗

[Effects of smoking on pulmonary function: a cross-sectional and longitudinal study].

Cross-sectional and longitudinal studies were done to investigate the influence that a change in smoking habit can have on the pulmonary function. Seventeen hundred and thirty nine people (698 men, 1,041 women), 39 years of age or older, from the population of a farming village located in the central part of Miyazaki Prefecture were examined. A population-based cohort study with a 4-time observation was done over an interval of 12 years. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1.0) were used as the index of respiratory function, and adjusted annual change of FVC and adjusted annual change of FEV1.0 were used as a pulmonary function inspection index. There was a statistical significance in both %FVC and %FEV1.0 to the predicted values between smokers and non-smokers at the beginning of observation. The adjusted annual change of FVC both of male- and female-smokers and the adjusted annual change of FEV1.0 of male-smokers was higher than those of non-smokers in the longitudinal study. Percent FVC, %FEV1.0 and the adjusted FEV1.0 change of former male-smokers were lower than those of continuing smokers. In addition to %FVC and %FEV1.0, annual change of FVC and annual change of FEV1.0 were important predictors of pulmonary function related to cigarette smoking.

Adult↗

Ligand-induced changes in the Streptomyces lividans TipAL protein imply an alternative mechanism of transcriptional activation for MerR-like proteins.

TipAL is a Streptomyces transcriptional activator assigned to the MerR/SoxR family based both on homology within its putative DNA recognition domain and the fact that its operator binding sites lie within a region of its promoter normally occupied by RNA polymerase. The tipA gene is also independently translated as the C-terminal ligand-binding domain of TipAL (TipAS; residues 111-254). Both TipAS and TipAL share broad recognition specificity for cyclic thiopeptide antibiotics. The molecular mechanism by which TipAL catalyzes prokaryotic transcriptional activation at the tipA promoter (ptipA) in response to thiostrepton was studied using a combination of analytical ultracentrifugation (AU), circular dichroism (CD), optical waveguide lightmode spectroscopy (OWLS; a sensitive in situ binding assay), and mutational analyses. AU showed that TipAL, but not TipAS, was a dimer in solution in the presence or absence of thiostrepton. This indicated that activation of TipAL by thiostrepton was not mediated by changes in multimerization and mapped the dimerization domain to its N-terminal 110 amino acids, presumably within amino acids predicted to form a coil-coil domain (residues 77-109). CD spectra showed that TipAL had more alpha-helical content than TipAS, probably because of the presence of the additional N-terminal region. The helicity of TipAL and TipAS both increased slightly after binding thiostrepton demonstrating conformation changes upon thiostrepton binding. OWLS experiments determined the overall binding constants via measurements of association and dissociation rates for both TipA proteins and RNA polymerase with ptipA. Thiostrepton slightly enhanced the rate of specific association of TipAL with ptipA, but drastically lowered the rate of dissociation from the binding site. TipAL-thiostrepton increased the affinity of RNA polymerase for ptipA more than 10-fold. In conjunction with genetic experiments, we propose that, while there are some similarities, the mechanism by which TipAL activates transcription is distinctly different from the established MerR/SoxR paradigm.

Bacterial Proteins↗

Studies toward the total synthesis of popolohuanone E: enantioselective synthesis of 8-O-methylpopolohuanone E.

[structure: see text]. 8-O-methylpopolohuanone E (2) was synthesized in a highly convergent manner starting from the cis-fused decalin derivative accessible from the (-)-Wieland-Miescher ketone analogue. The synthetic method features a biogenetic-type annulation of the phenolic and quinone segments to regioselectively construct the central tricyclic ring system as the key step.

Enzyme Inhibitors↗

Impact of genetic polymorphisms of 17-hydroxylase cytochrome P-450 (CYP17) and steroid 5alpha-reductase type II (SRD5A2) genes on prostate-cancer risk among the Japanese population.

Steroid hormones, especially testosterone, play important roles in the carcinogenesis of prostate cancer, and several studies have reported changes in risk with polymorphisms of genes involved in steroid metabolism. One example is the CYP17 gene, which has a polymorphic T-to-C substitution in the 5'-untranslated region giving rise to A1 (T) and A2 (C) alleles. Steroid 5alpha-reductase type II (SRD5A2), which converts testosterone to the metabolically more active dihydrotestosterone, exhibits 2 polymorphisms: V89L, which substitutes leucine for valine at codon 89, and A49T, which substitutes threonine for alanine at codon 49. We therefore designed a case-control study of 105 prostate-cancer patients and 210 controls with benign prostatic hyperplasia for the purpose of investigating the association between prostate-cancer risk and polymorphisms in the SRD5A2 and CYP17 genes among the Japanese. The frequency of the CYP17 A2/A2 genotype in cases (18.8%) was higher than in controls (14.5%). Compared with the A1/A1 genotype, the odds ratio for the A2/A2 genotype was 2.39 (95% confidence interval 1.04-5.46, p = 0.04). The frequency of the SRD5A2 LL genotype in cases (29.3%) was also slightly higher than in controls (24.6%), but this was not significant. Regarding the A49T polymorphism of SRD5A2, we could not detect the T allele in any of the examined samples. These data suggest a significant association between the CYP17 polymorphism and prostate-cancer risk among the Japanese.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Studies toward the total synthesis of scyphostatin: first entry to the highly functionalized cyclohexenone segment.

The cyclohexenone segment 2 of scyphostatin (1), a potent inhibitor of neutral sphingomyelinase, was synthesized in an enantioselective manner starting from the bromo ether 5 and D-serinal derivative 3. The synthetic method features a coupling reaction of 5 with 3 to construct the asymmetric quaternary carbon center and a stereospecific epoxide ring formation as the key steps.

Amides↗

Genetic polymorphisms in cytochrome P450 (CYP) 1A1, CYP1A2, CYP2E1, glutathione S-transferase (GST) M1 and GSTT1 and susceptibility to prostate cancer in the Japanese population.

Associations between genetic polymorphisms of CYP1A1, CYP1A2, CYP2E1, GSTM1 and GSTT1 and prostate cancer (PCa) were analyzed in a case-control study of 315 individuals. The frequency of valine (Val)/valine (Val) genotypes for CYP1A1 was 11.3% in cases compared with 5.5% in controls, this polymorphism thus being associated with a significantly increased risk of PCa (odds ratio=2.4, 95% confidence interval (CI)=1.01-5.57). No links were detected between PCa and polymorphisms in other enzymes. However, the combination of CYP1A1 (Ile/Val and/or Val/Val) polymorphisms with the GSTM1 null type resulted in an OR of 2.2 (CI=1.10-4.57, 1.12-4.20, respectively). This study suggests that the CYP1A1 polymorphism and its combination with GSTM1 may be associated with PCa susceptibility in the Japanese population.

Case-Control Studies↗

Radiotherapy after hyperbaric oxygenation improves radioresponse in experimental tumor models.

We examined the effect of radiotherapy after hyperbaric oxygen (HBO) breathing in experimental tumors using a tumor growth delay assay. Tumor models used were SCCVII (radiobiological hypoxic fraction: approximately 10%) and 9L tumors (containing less hypoxic cells) subcutaneously transplanted into C3H/He mice and Fisher 344 rats, respectively. Irradiation using X-rays was locally administered to the tumors immediately after decompression. HBO breathing enhanced the radiation response in SCCVII tumors but not in 9L ones. In the next experiment using SCCVII tumors, irradiation was administered 5, 15, 30, and 90 min after decompression. A significant growth delay was seen in the treated animals within 30 min after HBO breathing, and the tumor growth delay time was prolonged 1.61 times as long as that in radiotherapy alone. We concluded that: (1) radiotherapy after HBO breathing is effective for tumors with hypoxic cells; and (2) the time lapse from decompression to irradiation is an important factor in improving radiosensitivity. Radiotherapy after HBO breathing can be used to enhance the efficacy of clinical treatments.

Animals↗

Stress caused by minimally invasive cardiac surgery versus conventional cardiac surgery: incidence of systemic inflammatory response syndrome.

The present study was conducted to evaluate the degree of stress in patients induced by minimally invasive cardiac surgery (MICS) in comparison with that caused by conventional cardiac surgery. We did this by assessing the incidence of systemic inflammatory response syndrome (SIRS). A total of 48 adult patients who underwent surgery for single valve disease were included in this study, 27 of whom underwent conventional surgery and 21 MICS. We evaluated the stress inflicted on the patients in these two groups by analyzing the duration and degree of SIRS and the level of C-reactive protein (CRP). SIRS was assessed by measuring body temperature, heart rate, respiratory rate, and white blood cell counts. There were no significant differences in the operating times, perfusion times, or aorta clamp times between the two groups; and the mean volume of blood transfusion did not differ significantly either. There was no significant difference in the incidence of SIRS or the mean duration of SIRS between the two groups. The CRP levels did not differ significantly between the two groups. Thus although MICS is superior to conventional cardiac surgery in that only a small skin incision is required, the stress experienced by the patient may be the same as that experienced by the patient undergoing conventional cardiac surgery.

Aged↗

Development of the fluorometric ELISA method for determination of alpha1-microglobulinuria in a cadmium-polluted area in Japan.

OBJECTIVES: To evaluate the usefulness of a newly developed fluorometric enzyme-linked immunosorbent assay (fluorometric ELISA) method for quantification of alpha1 -microglobulin (alpha1-m, protein HC) in an epidemiological study. METHODS: Urinary alpha1-m in 37 female inhabitants in a cadmium-polluted area, including seven cases with Itai-itai disease, and ten inhabitants in a non-polluted area in Japan were examined. The alpha1-m was measured by both the fluorometric ELISA and a commercially available enzyme immunoassay (EIA) method to evaluate correlation of the two measurements. Concentration of beta2-microglobulin (beta2-m) was also determined in the same samples. RESULTS: The detection limit of this method was 3 ng/ml or less of alpha1-m. A significant, high positive correlation was obtained between the alpha1-m concentrations measured with the fluorometric ELISA and that of EIA (r = 0.95, P < 0.0001). A significant association was also shown between the alpha1-m and beta2-m concentrations in the urine samples. The concentrations of urinary alphal-m of the inhabitants in the cadmium-polluted area (mean: 6.21 mg/l, 95% confidence interval (95% CI): 4.06-9.50 mg/l) were significantly higher than those of the reference area (mean: 2.19 mg/l, 95% CI: 1.90-2.67 mg/l). The urinary alpha1-m level of the Itai-itai patients was shown to be highest at 39.63 mg/l (95% CI: 28.27 55.55 mg/l). When the cut-off value of 10 mg/l was employed, alpha1-m had a sensitivity of 100% and specificity of 100% for Itai-itai disease. CONCLUSION: These results suggest that this fluorometric ELISA is a useful tool to determine urinary alpha1-m in the epidemiological survey of renal tubular dysfunction, especially in the cadmium-polluted area of Japan.

Aged↗

Apparent bradycardia-dependent right bundle branch block associated with atrial fibrillation: concealed electrotonic conduction as a possible mechanism.

A 79-year-old woman with atrial fibrillation was reported in whom apparent bradycardia-dependent right bundle branch block was suggested. When a conducted supraventricular impulse occurred within a critical period after the preceding conducted impulse, the impulse was blocked in the right bundle branch except when it fell in the supernormal period of the right bundle branch. When the conducted impulse occurred between the critical period and another longer period, it was conducted without bundle branch block. When the impulse occurred beyond that longer period, it was usually blocked in the bundle branch again. However, when the impulse occurred beyond a still longer period, it was conducted without bundle branch block again. These findings suggest that when impulses fell in the right bundle branch shortly after the preceding conducted impulses, they were blocked in both bundle branches; however, it seemed that concealed electrotonic conduction of the blocked impulses affected conduction of the subsequent impulses.

Aged↗

Repetitive supernormal conduction in the right bundle branch in high degree bilateral bundle branch block.

Electrocardiograms were taken from a 67-year-old woman with high-degree atrioventricular block in which ventricular escape beats of right bundle branch block pattern occurred, accompanying occasional ventricular capture beats. Only when a sinus P wave occurred 0.60 s after the preceding escape beat, it was followed by a capture beat of left bundle branch block pattern with the RP interval of 0.60 s and the PR interval of 0.19 s. Similar left bundle branch block with left axis deviation pattern had been shown in the electrocardiogram taken 2 years before. Such RP and PR intervals in capture beats were invariable. These suggest that capture beats occurred as a result of supernormal conduction in the right bundle branch, which denies the possibility of ventricular extrasystoles. Such capture beats with the above RP and PR intervals were observed repeatedly.

Aged↗

Ventricular parasystolic couplets originating in the pathway between the ventricle and the parasystolic pacemaker: mechanism of "irregular" parasystole.

This article explains the mechanism of "irregular" parasystole. Two theories have been suggested: "electrotonic modulation" and "type I second degree entrance block." This study attempts to clarify the mechanism of irregular parasystole in cases of true ventricular parasystole associated with ventricular parasystolic couplets. Cases associated with ventricular parasystolic couplets were selected from 37 clinical cases of true ventricular parasystole in which one or more pure parasystolic cycles with no intervening nonectopic QRS complexes were found. Of the 37 cases of true ventricular parasystole, ventricular parasystolic couplets were found in 4 cases. In none of the other 33 cases, ventricular parasystolic couplets were found. In all the cases coexisting with ventricular parasystolic couplets, the latter ectopic QRS complex of the couplet failed to reset the parasystolic rhythm. The above findings suggest that the latter ectopic QRS complex of the parasystolic couplet originated not in the parasystolic pacemaker but in the pathway between the ventricle and the parasystolic pacemaker. It seems that when a sinus impulse fell late in the parasystolic cycle, it passed through the site of second degree entrance block and that the parasystolic couplets originated from the reentrant pathway between the ventricle and the pacemaker. This strengthens our previous suggestion that the mechanism of irregular parasystole is governed by "type I second degree entrance block" and not by "electrotonic modulation."

Aged↗

Two new modes of smooth muscle myosin regulation by the interaction between the two regulatory light chains, and by the S2 domain.

Previous studies indicated that single-headed smooth muscle myosin and S1 (a single head fragment) are not regulated through phosphorylation of the regulatory light chain (RLC). To investigate the importance of the double-headedness of myosin and of the S2 region for the phosphorylation-dependent regulation, we made three types of recombinant mutant smooth muscle HMMs with one intact head and an N-terminally truncated head. The truncated head of Delta MD lacked the motor domain, that of Delta(MD+ELC) lacked the motor and essential light chain binding domains, and single-headed HMM had one intact head alone. The basal ATPase activities of the three mutants decreased as the KCl concentration became less than 0.1 M. Such a decrease was not observed for S1, which had no S2 region, suggesting that S2 is necessary for this myosin behavior. This activity decrease also disappeared when RLCs of Delta MD and Delta(MD+ELC), but that of single-headed HMM, were phosphorylated. When their RLCs were unphosphorylated, the three mutants exhibited similar actin-activated ATPase levels. However, when they were phosphorylated, the actin-activated ATPase activities of Delta MD and Delta(MD+ELC) increased to the S1 level, while that of single-headed HMM remained unchanged. Even in the phosphorylated state, the actin-activated ATPase activities of the three mutants and S1 were much lower than that of wild-type HMM. We propose that S2 has an inhibitory function that is canceled by an interaction between two phosphorylated RLCs. We also propose that a cooperative interaction between two motor domains is required for a higher level of actin activation.

Actins↗

Functional role of the C-terminal domain of smooth muscle myosin light chain kinase on the phosphorylation of smooth muscle myosin.

Smooth muscle myosin light chain kinase (MLCK) is known to bind to thin filaments and myosin filaments. Telokin, an independently expressed protein with an identical amino acid sequence to that of the C-terminal domain of MLCK, has been shown to bind to unphosphorylated smooth muscle myosin. Thus, the functional significance of the C-terminal domain and the molecular morphology of MLCK were examined in detail. The C-terminal domain was removed from MLCK by alpha-chymotryptic digestion, and the activity of the digested MLCK was measured using myosin or the isolated 20-kDa light chain (LC20) as a substrate. The results showed that the digestion increased K(m) for myosin 3-fold whereas it did not change the value for LC20. In addition, telokin inhibited the phosphorylation of myosin by MLCK by increasing K(m) but only slightly increased K(m) for LC20. Electron microscopy indicated that MLCK was an elongated molecule but was flexible so as to form folded conformations. MLCK was crosslinked to unphosphorylated heavy meromyosin with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide in the absence of Ca(2+)/calmodulin (CaM), and electron microscopic observation of the products revealed that the MLCK molecule bound to the head-tail junction of heavy meromyosin. These results suggest that MLCK binds to the head-tail junction of unphosphorylated myosin through its C-terminal domain, where LC20 can be promptly phosphorylated through its catalytic domain following the Ca(2+)/CaM-dependent activation.

Animals↗