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Biomedical subjects

H Yamazaki

Publications and source records attributed to H Yamazaki.

At least 37 records · Page 2Linked to original sources
PubMed2003

Recognition of left ventricular hypertrophy in new recruits of professional sumo wrestling.

The efficacy of electrocardiography (ECG) in the diagnosis of left ventricular (LV) hypertrophy in 890 males, newly recruited to Japanese professional sumo wrestling (15.9 +/- 1.8 years of age, 177.8 +/- 4.7cm, 107.3 +/- 4.7kg), was tested by comparing simple, widely employed ECG criteria (Sokolow-Lyon chest and limb lead voltages and Cornell voltage with repolarisation criteria) with echocardiographic evaluations of LV mass indexed to body surface area. LV hypertrophy was defined as a LV mass index > 2 SD above the mean value obtained from 115 age-matched, normotensive, sedentary, male controls. The prevalence of LV hypertrophy as determined by echocardiography was 9.0% the entire group and was 8.3% among the 484 normotensives. The sensitivities of the three ECG criteria were < or = 36.0%, and their specificities were 70.0-99.0%. In contrast to the Sokolow-Lyon chest lead criteria, the diagnostic performance of the Cornell criteria was little affected by body mass index (BMI), and stepwise regression revealed that BMI did not significantly correlate with Cornell voltage. Still, the diagnostic efficacy of ECG was not sufficient to merit its use for primary recognition of LV hypertrophy among professional sumo wrestlers. Indeed, LV hypertrophy will likely go undetected by ECG in most overweight muscular athletes.

Adolescent↗
PubMed2003

Catalytic activities of cytochrome P450 enzymes and UDP-glucuronosyltransferases involved in drug metabolism in rat everted sacs and intestinal microsomes.

1. The use of everted sacs of the small intestine as an enzyme source for studying the metabolism of xenobiotics by cytochrome P450 (P450, CYP) enzymes and UDP-glucuronosyltransferases has been investigated. 2. Most of the drug oxidation activities for testosterone, bufuralol, ethoxyresorufin and 7-ethoxycoumarin resided in the upper part of the everted sacs and in intestinal microsomes. Testosterone 6 beta-hydroxylase activities in the everted sacs were about two times higher than those in the intestinal microsomes. By freezing and thawing treatment, the testosterone 6 beta- and 16 alpha-hydroxylase activities of the everted sacs were considerably decreased, and those of the intestinal microsomes were abolished. 3. Microsomal testosterone 6 beta-hydroxylation, bufuralol 1'-hydroxylation, and pentoxyresorufin and ethoxyresorufin O-dealkylation were inhibited by ketoconazole, quinine, metyrapone and alpha-naphthoflavone respectively. Immunoreactive proteins using anti-CYP2B1 and anti-CYP3A2 antibodies were detected in the upper and middle parts of the rat small intestine. 4. Except for morphine 3-glucuronidation, glucuronidation activities in intestinal microsomes or everted sacs were not dependent on the intestinal region. The lower part of the everted sacs exhibited about 10 times higher morphine-3-glucuronidation activities compared with those of the upper part. The glucuronidation activities of 4-nitrophenol in the everted sacs were 10 times higher than those in microsomes. 5. These results demonstrated that the upper part of rat small intestine serves as the major site for intestinal P450-mediated first-pass metabolism. CYP3A enzymes in rat intestinal microsomes may not be stable but probably play an important role in drug oxidations. The high activity of glucuronidation in the rat small intestine should also be considered in terms of drug metabolism.

Adrenergic beta-Antagonists↗
PubMed2002

A combination of heparin and an intermittent pneumatic compression device may be more effective to prevent deep-vein thrombosis in the lower extremities after laparoscopic cholecystectomy.

BACKGROUND: The purpose of this study was to clarify the effect of a combination of heparin and an intermittent pneumatic compression device on thrombogenesis and platelet activation in the upper and lower extremities after laparoscopy. METHODS: A blinded study was performed on 30 patients. Patients were randomly injected with either heparin or physiological saline solution (PSS) subcutaneously. The intermittent compression boot was used during surgery. Plasma D-dimer (D-D), a marker of thrombogenesis, and b-thromboglobulin (b-TG), a marker of platelet activation, were measured in the upper and lower extremities. RESULTS: In the heparin group, D-Ds in the upper and lower extremities increased significantly 24 h after surgery, but they were significantly lower than those of the PSS group. b-TG in the lower extremities of patients in the PSS group increased significantly 24 h after surgery. CONCLUSION: A combination of low-molecular-weight heparin and intermittent pneumatic compression may be more effective to prevent deep-vein thrombosis in the legs.

Adult↗
PubMed2002

Renal cortical retention of contrast medium on delayed CT and nephropathy following transcatheter arterial chemoembolisation in patients with high serum creatinine level.

The aim of this study was to investigate the prevalence of renal cortical retention (RCR) of contrast media seen on delayed CT, and nephropathy following transarterial chemoembolisation (TACE) in high-risk patients. The findings of 18 patients with abnormally high serum creatinine levels who underwent TACE were reviewed. Nephropathy was defined as an increase in serum creatinine level of more than 44 micromol l(-1), or more than 25%, on day 1, 3, 7 or 14. RCR was defined as mild (CT value >50) or severe (CT value >100). RCR was seen in 16 cases (89%) and in seven cases (39%) of post-TACE nephropathy. Patients without severe RCR did not develop nephropathy post-TACE, whereas 50% of those with such retention did (p=0.19). Delayed CT appears to have the potential as an early detector of nephropathy post-TACE in high-risk patients.

Adult↗
PubMed2001

Cytotoxicity and apoptosis produced by troglitazone in human hepatoma cells.

Troglitazone is an antidiabetic agent that increases the insulin sensitivity of target tissues in non-insulin-dependent diabetes mellitus. It has been reported that troglitazone causes severe hepatic injury in certain individuals. In the present study, the mechanism for the hepatic injury by troglitazone was investigated with human hepatoma cell lines. HepG2 cells were incubated with troglitazone, its metabolites M-1 (sulfate), M-2 (gulucronide), M-3 (quinone), and other thiazolidinediones (pioglitazone and rosiglitazone). Troglitazone exhibited time- and concentration-dependent cytotoxicity and M-3 also exhibited weak cytotoxicity. Troglitazone induced apoptotic cell death characterized by internucleosomal DNA fragmentation and nuclear condensation. As other thiazolidinediones, pioglitazone and rosiglitazone, did not induce cell death and apoptosis in the present study, the affinity to PPARgamma may not affect the induction of apoptosis by troglitazone. These results suggest that troglitazone induces apoptotic hepatocyte death which it may be one of the factors of liver injury in humans.

Apoptosis↗
PubMed2001

Metabolic activation of carcinogenic 1-nitropyrene by human cytochrome P450 1B1 in Salmonella typhimurium strain expressing an O-acetyltransferase in SOS/umu assay.

Metabolic activation of 1-nitropyrene (1-NP) by human cytochrome P450 (P450) family 1 enzymes co-expressed with NADPH-cytochrome P450 reductase (NPR) in Escherichia coli membranes was investigated. 1-NP induced umu gene expression in Salmonella typhimurium TA1535/pSK1002 in the absence of any P450 system, but the activities were influenced by the levels of bacterial O-acetyltransferase (OAT) and nitroreductase. Metabolic activation of 1-NP by human P450 1B1/NPR membranes was observed and was influenced by the levels of OAT levels in tester strains. Metabolic activation of 1-NP (0.3microM) by P450 1B1 was 750 umu units/min/nmol P450 1B1 in an OAT-overexpressing strain NM2009. The metabolic activation of 1-NP (3-30microM) was similar (approximately 300 umu units/min/nmol P450 1B1) using TA1535/pSK1002 or OAT-deficient strain NM2000. P450 1B1 had the highest catalytic activities among P450 family 1 enzymes for the activation of 1-aminopyrene (1-AP) in the OAT-overexpressing strain NM2009, suggesting nitrenium ion formation via N-hydroxylation/O-acetylation. High-performance liquid chromatography (HPLC) analyses revealed the formation of 1-nitropyrene-6-ol and also 1-nitropyrene-3-ol, 1-nitropyrene-8-ol, and trans-4,5-dihydroxy-4,5-diol-1-nitropyrene from 1-NP (10microM), catalyzed by P450 1B1. These results indicate that 1-NP can be activated by human P450 1B1 to a genotoxic agent by nitroreduction/O-acetylation at low substrate concentrations and probably by epoxidation (independent of OAT) at high concentrations.

Acetyltransferases↗
PubMed2001

Hybrid capture-II and LCR-E7 PCR assays for HPV typing in cervical cytologic samples.

As part of an ongoing cohort study in the Hokuriku region of Japan, cervical cell samples from histologically confirmed normal (n = 114) or abnormal (n = 286) women were examined for the presence of HPV DNA using a second-generation hybrid capture assay (HCA-II) and LCR-E7 PCR. HCA-II detected low-risk (HPV-6, -11, -42, 43 and -44) and high-risk (HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59 and -68) HPV types, while LCR-E7 PCR detected an additional 7 HPV types and some uncharacterized types. In screening of high-grade squamous intraepithelial lesions (HSILs) and invasive cervical cancer, the sensitivities of HCA-II and LCR-E7 PCR testing the high-risk HPV types were 83% and 81%, respectively, while the specificity of both assays was 93%. The sensitivity of LCR-E7 PCR increased to 87%, which was significantly higher than that in HCA-II, when testing both high-risk and other HPV types. Sixty-eight inconsistent results (17% of total tested) from HCA-II and LCR-E7 PCR were due to (i) low copy number of HPV genome (false-negative for HCA-II, 5.3% and for LCR-E7 PCR, 1.3%), (ii) infection with HPV types undetectable by HCA-II (4.8%), (iii) multiple HPV infections (5%) or (iv) unknown reasons (0.8%). LCR-E7 PCR revealed that infections with HPV-16, -18, -31, -33, -35, -51, -52, -56, -58 or -67 was a high risk for cancer since these types predominated in HSIL and invasive cervical cancer. Samples showing high relative light units (>20) with a high-risk probe in HCA-II also gave positive results in LCR-E7 PCR and were generally associated with abnormal cervical lesions. Thus, we propose that both HCA-II and LCR-E7 PCR are valuable screening tests for premalignant and malignant cervical lesions.

Case-Control Studies↗
PubMed2001

Type-specific regulation of adenylyl cyclase. Selective pharmacological stimulation and inhibition of adenylyl cyclase isoforms.

Crystallographic studies have elucidated the binding mechanism of forskolin and P-site inhibitors to adenylyl cyclase. Accordingly, computer-assisted drug design has enabled us to identify isoform-selective regulators of adenylyl cyclase. After examining more than 200 newly synthesized derivatives of forskolin, we found that the modification at the positions of C6 and C7, in general, enhances isoform selectivity. The 6-(3-dimethylaminopropionyl) modification led to an enhanced selectivity for type V, whereas 6-[N-(2-isothiocyanatoethyl) aminocarbonyl] and 6-(4-acrylbutyryl) modification led to an enhanced selectivity for type II. In contrast, 2'-deoxyadenosine 3'-monophosphate, a classical and 3'-phosphate-substituted P-site inhibitor, demonstrated a 27-fold selectivity for inhibiting type V relative to type II, whereas 9-(tetrahydro-2-furyl) adenine, a ribose-substituted P-site ligand, showed a markedly increased, 130-fold selectivity for inhibiting type V. Consequently, on the basis of the pharmacophore analysis of 9-(tetrahydro-2-furyl) adenine and adenylyl cyclase, a novel non-nucleoside inhibitor, 2-amino-7-(2-furanyl)-7,8-dihydro-5(6H)-quinazolinone (NKY80), was identified after virtual screening of more than 850,000 compounds. NKY80 demonstrated a 210-fold selectivity for inhibiting type V relative to type II. More importantly, the combination of a type III-selective forskolin derivative and 9-(tetrahydro-2-furyl) adenine or NKY80 demonstrated a further enhanced selectivity for type III stimulation over other isoforms. Our data suggest the feasibility of adenylyl cyclase isoform-targeted regulation of cyclic AMP signaling by pharmacological reagents, either alone or in combination.

Adenylyl Cyclase Inhibitors↗
PubMed2001

Glutamic acid decarboxylase-immunoreactivity of bulbar respiratory neurons identified by intracellular recording and labeling in rats.

To distinguish the GABAergic neuron in the ventral respiratory group (VRG) of rats, immunohistochemical staining of glutamic acid decarboxylase (GAD) was performed in neurons that had been individually identified by in vivo intracellular recording and labeling with neurobiotin. A total of five types of respiratory neurons were identified and labeled; augmenting inspiratory (aug-I, n=12), decrementing or early inspiratory (early-I, n=3), inspiration-expiration phase spanning or late inspiratory (late-I, n=3), decrementing expiratory or postinspiratory (PI, n=8), and augmenting or stage 2 expiratory (E2, n=3). In addition, expiration-inspiration phase-spanning or pre-inspiratory neurons (pre-I, n=2) were recorded, but not labeled. The membrane potential trajectory of each neuron type resembled that previously described in cat, suggesting a comparable neuronal organization between the two species. According to the axonal arborization, those labeled neurons were further classified as propriobulbar (6 aug-I, all early-I, all late-I, and 3 PI), bulbospinal (2 aug-I and all E2) and cranial-motor neurons (4 aug-I and 5 PI). GAD-immunoreactivity was consistently detected in the propriobulbar neurons, while it was not seen in cranial-motor and bulbospinal neurons. In addition, GAD-immunoreactive varicosities were found surrounding the somatic and dendritic surface of all labeled neurons. The present results illustrate that the propriobulbar types of early-I, aug-I, late-I and PI neurons are GABAergic inhibitory neurons and virtually all types of respiratory neurons receive GABAergic inputs in the rat's VRG.

Action Potentials↗
PubMed2001

Phase III trial of high- vs. low-dose-rate interstitial radiotherapy for early mobile tongue cancer.

PURPOSE: Early mobile tongue cancer can be controlled with interstitial radiotherapy (ISRT). We carried out a Phase III trial to compare the treatment results of low-dose-rate (LDR) ISRT and high-dose-rate (HDR) ISRT for early mobile tongue cancer. METHODS AND MATERIALS: From April 1992 through October 1996, 59 patients with cancer of the early mobile tongue were registered in this Phase III study. Eight patients were excluded from the evaluation because of violations of the requirements for this study. Of 51 eligible patients, 26 patients were treated with LDR-ISRT (70 Gy/4-9 days) and 25 patients with HDR-ISRT (60 Gy/10 fractions/1 week). For the hyperfractionated HDR-ISRT, the time interval between 2 fractions was more than 6 h. RESULTS: Five-year local control rates of the LDR and HDR groups were 84% and 87% respectively. Nodal metastasis occurred in 6 patients in each group. Five-year nodal control rates of the LDR and HDR groups were 77% and 76%, respectively. CONCLUSION: Hyperfractionated HDR-ISRT for early mobile tongue cancer has the same local control compared with continuous LDR-ISRT. Hyperfractionated HDR-ISRT is an alternative treatment for continuous LDR-ISRT.

Adult↗
PubMed2001

Reversal of cisplatin and multidrug resistance by ribozyme-mediated glutathione suppression.

gamma-Glutamylcysteine synthetase (gamma-GCS) is a key enzyme in glutathione (GSH) synthesis, and is thought to play a significant role in intracellular detoxification, especially of anticancer drugs. Increased levels of GSH are commonly found in the drug-resistant human cancer cells. We designed a hammerhead ribozyme against gamma-GCS mRNA (anti-gamma-GCS Rz), which specifically down-regulated gamma-GCS gene expression in the HCT-8 human colon cancer cell line. The aim of this study was to reverse the cisplatin and multidrug resistance for anticancer drugs. The cisplatin-resistant HCT-8 cells (HCT-8DDP cells) overexpressed MRP and MDR1 genes, and showed resistance to not only cisplatin (CDDP), but also doxorubicin (DOX) and etoposide (VP-16). We transfected a vector expressing anti-gamma-GCS Rz into the HCT-8DDP cells (HCT-8DDP/Rz). The anti-gamma-GCS Rz significantly suppressed MRP and MDR, and altered anticancer drug resistance. The HCT-8DDP/Rz cells were more sensitive to CDDP, DOX and VP-16 by 1.8-, 4.9-, and 1.5-fold, respectively, compared to HCT-8DDP cells. The anti-gamma-GCS Rz significantly down-regulated gamma-GCS gene expression as well as MRP/MDR1 expression, and reversed resistance to CDDP, DOX and VP-16. These results suggested that gamma-GCS plays an important role in both cisplatin and multidrug resistance in human cancer cells.

Antineoplastic Agents↗
PubMed2001

Wnt signaling regulates hemopoiesis through stromal cells.

Hemopoietic cells develop in a complex milieu that is made up of diverse components, including stromal cells. Wnt genes, which are known to regulate the fate of the cells in a variety of tissues, are expressed in hemopoietic organs. However, their roles in hemopoiesis are not well characterized. In this study, we examined the roles of Wnt proteins in hemopoiesis using conditioned medium containing Wnt-3a. This conditioned medium dramatically reduced the production of B lineage cells and myeloid lineage cells, except for macrophages in the long-term bone marrow cultures grown on stromal cells, although the sensitivity to the conditioned medium differed, depending on the hemopoietic lineage. In contrast, the same conditioned medium did not affect the generation of B lineage or myeloid lineage cells in stromal cell-free conditions. These results suggested that Wnt proteins exert their effects through stromal cells. Indeed, these effects were mimicked by the expression of a stabilized form of beta-catenin in stromal cells. In this study, we demonstrated that Wnt signaling regulates hemopoiesis through stromal cells with selectivity and different degrees of the effect, depending on the hemopoietic lineage in the hemopoietic microenvironment.

Animals↗
PubMed2001

Stimulation of cytochrome P450 reactions by apo-cytochrome b5: evidence against transfer of heme from cytochrome P450 3A4 to apo-cytochrome b5 or heme oxygenase.

Many cytochrome P450 (P450)-dependent reactions have been shown to be stimulated by another microsomal protein, cytochrome b(5) (b(5)). Two major explanations are (i) direct electron transfer from b(5) and (ii) a conformational effect in the absence of electron transfer. Some P450s (e.g. 3A4, 2C9, 17A, and 4A7) are stimulated by either b(5) or b(5) devoid of heme (apo-b(5)), indicating a lack of electron transfer, whereas other P450s (e.g. 2E1) are stimulated by b(5) but not by apo-b(5). Recently, a proposal has been made by Guryev et al. (Biochemistry 40, 5018-5031, 2001) that the stimulation by apo-b(5) can be explained only by transfer of heme from P450 preparations to apo-b(5), enabling electron transfer. We have repeated earlier findings of stimulation of catalytic activity of testosterone 6beta-hydroxylation activities with four P450 preparations, in which nearly all of the heme was accounted for as P450. Spectral analysis of mixtures indicated that only approximately 5% of the heme can be transferred to apo-b(5), which cannot account for the observed stimulation. The presence of the heme scavenger apomyoglobin did not inhibit the stimulation of P450 3A4-dependent testosterone or nifedipine oxidation activity. Further evidence against the presence of loosely bound P450 3A4 heme was provided in experiments with apo-heme oxygenase, in which only 3% of the P450 heme was converted to biliverdin. Finally, b(5) supported NADH-b(5) reductase/P450 3A4-dependent testosterone 6beta-hydroxylation, but apo-b(5) did not. Thus, apo-b(5) can stimulate P450 3A4 reactions as well as b(5) in the absence of electron transfer, and heme transfer from P450 3A4 to apo-b(5) cannot be used to explain the catalytic stimulation.

Apoproteins↗
PubMed2001

Influence of age on the results of brachytherapy for early tongue cancer.

PURPOSE: To determine the influence of elder age on the results of brachytherapy for early (T1-2 N0 M0) oral tongue cancer and examine the compatibility of low-dose rate (LDR) with high-dose rate (HDR) brachytherapy. METHODS AND MATERIALS: We analyzed 591 patients treated at Osaka University Hospital between 1967 and 1999. We compared the results of radiotherapy for 156 elderly patients (137 LDR and 19 HDR) 65 years of age or older and 435 patients (383 LDR and 52 HDR) less than 65 years of age. RESULTS: HDR brachytherapy showed the same local control rate as LDR brachytherapy (81% at 3 years). Elderly patients showed a poorer local control rate (75% at 3 years) than the younger group (83% at 3 years)(p = 0.002). Multivariate analysis identified age as the only prognostic factor for local control (p = 0.002). CONCLUSIONS: HDR brachytherapy achieved the same result as LDR brachytherapy. However, the elderly patient showed a higher rate of local recurrence after brachytherapy.

Adult↗
PubMed2001

Mn K-edge XMCD in Mn3MC (M=Zn and Ga) perovskite.

Mn3MC (M=Zn and Ga) perovskite has attracted interest because of a variety of magnetic phase transitions. In this work, we measure temperature and magnetic field dependence of X-ray magnetic circular dichroism (XMCD) at Mn K-edge and discuss effect of second constituent metal on the magnetic states of Mn atoms. The spectrum in Mn3ZnC is characterized by a dispersion-type profile. In Mn3GaC, intensity of the positive peak at the edge is drastically reduced. The difference originates in charge transfer from Zn or Ga to Mn atoms. Temperature and magnetic field variations of the Mn K-edge XMCD spectrum suggest that orbital magnetic moments are closely related to the magnetic phase transition.

Journal Article↗
PubMed2001

Electronic states in Cu2MnX (X=Al, In, and Sn) Heusler alloy studied by XMCD and multiple scattering calculations.

X-ray magnetic circular dichroism (XMCD) has been measured at Mn and Cu K-edge in Cu2MnX (X=Al, In, and Sn) Heusler alloy. The Mn K-edge spectrum shows a dispersion-type profile and the Cu K-edge resembles the Mn spectrum, which suggests that polarization of the p unoccupied bands originates commonly in Mn 3d states. To reproduce the observed spectrum by full multiple scattering calculations. Madelung potential has been taken into account. Charge redistribution is an important factor for the electronic structure in Cu2MnX Heusler alloy.

Journal Article↗
PubMed2001

Temporal and spatial localization of osteoclasts in colonies from embryonic stem cells.

Osteoclasts are hematopoietic cells essential for bone resorption. To understand the process of osteoclastogenesis, we have developed a culture system that employs a stromal cell line, in which differentiation of osteoclasts from single embryonic stem (ES) cells occurs. This culture, which did not require any cell passaging or other manipulations, enabled us to investigate the temporal and spatial localization of the osteoclast lineage in the colonies formed from ES cells. Cells expressing tartrate-resistant acid phosphatase, a specific marker of the osteoclast lineage, were first detected on day 8, and subsequently became localized at the periphery of colonies and matured into multinucleated cells to resorb bone. Addition of macrophage colony-stimulating factor and osteoprotegerin-ligand, which are produced by stromal cells, promoted osteoclastogenesis in whole colonies, indicating that the location and maintenance of mature osteoclasts as well as the growth and differentiation of osteoclast precursors are regulated by these two factors.

Animals↗