Biomedical subjects

T Sakata

Publications and source records attributed to T Sakata.

At least 127 records · Page 7Linked to original sources

PubMed1999

Analysis of 45 episodes of arterial occlusive disease in Japanese patients with congenital protein C deficiency.

Hereditary protein C deficiency is associated with a predisposition to venous thrombosis. It is not clear whether the deficiency is involved in arterial occlusion. In the present study, we screened for protein C amidolytic activity in patients admitted to the National Cardiovascular Center Hospital, and we identified among them 43 probands and 51 relatives with heterozygous protein C deficiency. Among them, 34 patients with heterozygous protein C deficiency had manifested 45 episodes of arterial occlusive disease. Venous thrombotic diseases were less common. In the examination of whether protein C deficiency hastens arterial occlusion, we found a significant difference (p =0.02) in the age at onset of acute myocardial infarction between the patients with protein C deficiency (n=10; 49.4+/-14.8 years) and a group of patients with normal protein C levels (n=42; 60.5+/-10.6 years). Acute myocardial infarction occurred before 40 years of age in a significantly greater proportion of the patients with protein C deficiency (3:10, 30%) as compared with the controls (2:42, 5%) (chi2=5.9, p=0.015). At the onset of atherothrombotic cerebral infarction the patients with protein C deficiency were significantly (p=0.022) younger (n= 11; 57.4+/-12.8 years) than those with normal protein C levels (n=48; 64.6+/-10.1 years). Venous thrombosis was the most frequent clinical manifestation (21 of 31 episodes) in the patients with antithrombin III deficiency (n=26; 68% of the total), who were admitted to our hospital. Thus, our study suggests that congenital protein C deficiency contributes to earlier onset of arterial occlusive diseases, especially acute myocardial infarction, in Japanese subjects.

Adult↗

PubMed1999

The RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells.

Adrenomedullin, a potently hypotensive peptide isolated from human pheochromocytoma, is known to elicit a rise in cAMP levels within mammalian endothelial and smooth muscle cells. Until now, however, little has been known about the adrenomedullin receptor. Recently, a group called receptor activity-modifying proteins that complex with the calcitonin receptor-like receptor, and thereby regulate its transport and ligand specificity, were identified. Here we show that mRNA for both the calcitonin receptor-like receptor and the receptor activity-modifying protein 2, but not the receptor activity-modifying protein 1 or receptor activity-modifying protein 3, are expressed in human endothelial and vascular smooth muscle cells. We also found that adrenomedullin increased cAMP levels in HeLa EBNA and 293 EBNA cells, expressing both the receptor activity-modifying protein 2 and calcitonin receptor-like receptor proteins. Thus, the receptor activity-modifying protein 2/calcitonin receptor-like receptor complex apparently serves as a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells.

Adrenomedullin↗

PubMed1999

Molecular cloning of rat GADD45gamma, gene induction and its role during neuronal cell death.

To study the molecular mechanism of neuronal cell death, we carried out the screening of genes which were induced during the neuronal cell death of neuronal PC12. We cloned the cDNA of rat GADD45gamma, the third member of the GADD45 family. Induction of GADD45gamma mRNA was observed in the neuronal cell death caused by depletion of neurotrophic factor and Ca2+ ionophore treatment. Overexpression of GADD45gamma in superior cervical ganglion neurons caused cell death. These results suggest that GADD45gamma plays an important role in neuronal cell death.

Amino Acid Sequence↗

PubMed1999

A'-form RNA double helix in the single crystal structure of r(UGAGCUUCGGCUC).

Here we demonstrate the presence of the A'-RNA conformation using the single crystal structure of a tridecamer: r(UGAGCUUCGGCUC). The average A'-RNA conformation deduced from X-ray fiber diffraction data had only been available previously, but now the presence of the A'-RNA conformation has been found in a single crystal structure for the first time. Statistical analysis showed that the A'-RNA conformation is distinguishable from the A-RNA conformation in a plot of the major groove width against the base pair inclination angle. The major groove of the A'-RNA conformation is wide enough to accommodate a protein or peptide while that of the A-RNA conformation is too narrow to do so. The presence of the A'-RNA conformation is significant for protein-RNA interaction.

Crystallization↗

PubMed1999

A Case of Esophageal Squamous Cell Carcinoma Metastatic to the Breast.

Metastasis to the breast from extramammary malignancies is rare. There are especially few reports of metastasis from esophageal cancer. We report the pathological and autopsy findings of a 44-year-old man with advanced esophageal cancer and a left breast tumor. Squamous cell carcinoma invading the mammary glands wasdemonstrated histologically. Immunostains for ER, PgR, and ErbB-2 were negative. At autopsy, metastatic lesions were found in lung, liver, diaphragm, peritoneum, spine, and mediastinal lymph nodes, with no evidence of metastasis to the skin. While metastatic breast tumors are rarely the initial sign of malignancy, it isimportant to distinguish a metastasis from primary breast cancer to avoid unnecessary conflicting treatments.

Journal Article↗

PubMed1999

Alteration of heart uncoupling protein-2 mRNA regulated by sympathetic nerve and triiodothyronine during postnatal period in rats.

To provide tissue-specific and developmental characteristics of gene expression of rat heart uncoupling protein-2 (UCP2), we investigated developmental alterations of UCPs mRNA expression in the heart and brown adipose tissue (BAT), and examined possible up-regulators of heart UCP2 expression using in vitro studies. Heart UCP2 mRNA expression was low during the early postnatal days followed by a rapid and significant increase in the 2nd postnatal week. Heart UCP3 mRNA remained undetectable until the 2nd postnatal week when the expression reached a small but significant peak. BAT UCP1 mRNA was abundantly expressed in the neonate, but the expression rapidly decreased to the adult level. The studies using cultured cardiomyocytes demonstrated that both 10(-8) M triiodothyronine and 10(-7) M isoproterenol, but not phenylephrine, increased UCP2 mRNA expression. These results indicate that the sympathetic nervous system and/or thyroid hormones may be involved in the up-regulation of heart UCP2 gene expression during postnatal development. The increase in postnatal heart UCP2 may provide a key link between the postnatal energy shift and adaptation of rat pups to their novel environment.

Adipose Tissue, Brown↗

PubMed1999

Tumor necrosis factor-alpha regulates in vivo expression of the rat UCP family differentially.

A family of uncoupling proteins (UCPs), free fatty acid anion transporters, plays a crucial role in energy homeostatic thermoregulation. Tumor necrosis factor-alpha (TNF-alpha), a member of the cytokine family, is well known as an endogenous pyrogen. To evaluate the interaction of TNF-alpha with UCPs in thermogenesis, effects of TNF-alpha on rat UCP gene expression were examined in intrascapular brown adipose tissue (BAT), epididymal white adipose tissue (WAT) and soleus muscle (Muscle). Administration of TNF-alpha elevated rectal temperature by 0.7 degree C as well as serum leptin which peaked at 6 h, compared with saline controls. BAT UCP1 mRNA expression was increased by 1.2-fold at 6 h after the TNF-alpha treatment and decreased by 0.8-fold at 16 h after the treatment. In contrast to UCP1 expression in BAT, UCP2 mRNA expressions in BAT, WAT, and Muscle was increased to reach maximum levels of 1.3-, 1.6- and 1.8-fold, respectively, at 16 h after the treatment. UCP3 mRNA in Muscle, but not in BAT or WAT, was exclusively up-regulated by 1.7-fold at 16 h after the treatment. These results indicate that TNF-alpha up-regulates UCP gene expression differentially and tissue dependently, and add novel insights into thermogenesis under conditions of malignancy and inflammation.

Adipose Tissue↗

PubMed1999

Inhibition of Na(+)-K+ pump alleviates the shortening of action potential duration caused by metabolic inhibition via blockade of KATP channels in coronary perfused ventricular muscles of guinea-pigs.

The Na(+)-K+ pump is a consumer of intracellular ATP. We therefore examined whether blockade of the Na(+)-K+ pump by cardiac glycosides could inhibit ATP-sensitive K+ (KATP) channels and prolong the action potential duration (APD) of the guinea-pig ventricular muscles perfused with Tyrode's solution via the coronary artery and stimulated at 3 Hz. The metabolic inhibition (MI) achieved by application of 0.1 microM carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (a mitochondrial uncoupler) shortened the APD in a time-dependent manner. When dihydroouabain (DHO, 5 microM) was introduced 5 min but not 10 min after introduction of MI, the APD shortening was significantly attenuated. Application of glibenclamide (1 microM), a blocker of KATP channels, introduced both 5 and 10 min after MI also alleviated the APD shortening: DHO did not alleviate the APD shortening effect produced by cromakalim (5 microM), a KATP-channel opener. In separate experiments using whole-cell patch-clamp techniques, we found that this concentration of DHO (5 microM) depressed the Na(+)-K+ pump current of the guinea-pig ventricular myocytes from 210 to 100 pA (at 0 mV) or by 49.5%. We conclude that, during early phase (approximately 5 min) of MI, the APD shortening mostly results from the activation of KATP channels, and that even a approximately 50% inhibition of the Na(+)-K+ pump by DHO leads to the blockade of KATP channels and eventual lengthening of the APD.

Action Potentials↗

PubMed1999

H2-blocker modulates heart rate variability.

The use of H2-blockers in the treatment of patients with peptic ulcer has become popular. However, this treatment has adverse cardiovascular effects. The aim of this study was to investigate proarrhythmic rhythm and autonomic nervous activity by analyzing heart rate variability in patients treated with omeprazole, ranitidine, and plaunotol. Nineteen patients (mean age 67.5 +/- 2.7 years) with active gastric ulcer were treated with omeprazole (20 mg/day) for 8 weeks, then ranitidine (300 mg/day) for the next 4 months, and finally plaunotol (240 mg/day). At each stage of the treatment, Holter electrocardiography was performed, and heart rate variability and arrhythmias analyzed. Heart rate variability yielded power in the low- (0.04-0.15 Hz) and high-frequency components (0.15-0.4 Hz). Although both ranitidine and omeprazole induced little change in cardiac rhythm, the high-frequency power was higher (10.3 +/- 0.8 vs 8.6 +/- 0.6 ms, P < 0.05) and the ratio of low-to-high frequency power was lower (1.41 +/-0.10 vs 1.59 +/- 0.09. P < 0.05) during ranitidine than during plaunotol treatment. Cosinor analysis of heart rate variability revealed a decreased amplitude of low-frequency power during omeprazole compared with during ranitidine and plaunotol treatment. Ranitidine modulated high-frequency power which may be related to the adverse cardiovascular effects of H2-blocker.

Aged↗

PubMed1999

Evaluation of endoscopic injection sclerotherapy with and without simultaneous ligation for the treatment of esophageal varices.

For more effective and simple endoscopic injection sclerotherapy (EIS) for esophageal varices, we developed an EIS procedure with ligation (EISL) that is non-invasive, in which EIS and endoscopic variceal ligation (EVL) are performed simultaneously. In this study, we compared EISL and EIS in a randomized sample of patients (n = 14 for each procedure). For EISL, EVL was performed, including the injection site, after the injection of 5% ethanolamine oleate with iopamidol (EOI) into a varix. The mean number of treatment sessions required for eradication of esophageal varices was 2.3+/-0.5 for EISL and 3.9+/-0.8 for EIS (P < 0.001); the mean number of treatment sites was 6.2+/-2.2 for EISL and 14.0+/-5.0 for EIS (P < 0.001); the mean total amount of EOI used was 13.8+/-5.2ml for EISL and 26.3+/-9.8ml for EIS (P < 0.001). There were no significant differences in rates of recurrence of varices or in bleeding between the two groups. For EISL, fewer treatment sessions and less sclerosant were sufficient, probably because the sclerosants were more effective due to the blockage of variceal blood flow by the ligation. This method should provide a novel modification of EIS.

Endoscopy, Digestive System↗

PubMed1999

Novel germline mutations of the MEN1 gene in Japanese patients with multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors of the parathyroid glands, the pancreatic islet cells, and the anterior pituitary. Germline mutations of the MEN1 gene in three independent Japanese cases with MEN1 were analyzed. Case 1 has revealed a 2-bp (TA) insertion at nucleotide position 341 (341insTA) in exon 2, which shifts the reading frame such that the mutant protein has a completely different amino acid sequence from codon 78 to the premature stop codon at 119. In case 2, a nucleotide substitution, i.e., TAG in place of TGG, which encodes tryptophan at codon 198 was identified (nonsense mutation). These mutations were heterozygously present and have not been reported previously. Case 3 showed no mutations in the protein-coding exons and exon-intron junctions of the MEN1 gene by single-strand conformation polymorphism or direct sequencing of the polymerase chain reaction (PCR) fragments. We confirmed the finding that patients with MEN1 carry heterozygous germline mutations in the MEN1 gene, which is compatible with the idea that the MEN1 gene is a tumor suppressor gene. The reason why mutations in the coding region of the MEN1 gene could not be detected by PCR-based analysis in some of the MEN1 patients, e.g. case 3, needs to be clarified further.

Adult↗

PubMed1999

Noninvasive assessment of the cardiac baroreflex: response to downward tilting and comparison with the phenylephrine method.

OBJECTIVES: We studied the relation between changes in systolic blood pressure and RR interval during downward tilting in comparison with assessment of baroreflex sensitivity (BRS) measured by the phenylephrine method (Phe-BRS) and with measures of heart rate variability (HRV). BACKGROUND: The method most extensively used for assessing BRS involves bolus injections of phenylephrine. Several noninvasive methods proposed to assess BRS have not been widely applied in the clinical setting. METHODS: Sixteen healthy male volunteers were studied (mean age +/- SD 27.5+/-4.6 years). Arterial blood pressure using tonometry and electrocardiogram was simultaneously recorded. After 20 min of 70 degrees upright tilting, the table was returned to supine position at a speed of 3.2 degrees/s. Subsequently, BRS was assessed using an intravenous bolus injection of phenylephrine (2 to 3 microg/kg). Heart rate variability under resting conditions also was analyzed. RESULTS: In all subjects, a beat to beat systolic blood pressure increase associated with corresponding RR interval lengthening was observed during downward tilting as well as during phenylephrine administration. During both testing procedures, these two variables showed linear correlation, and the slope of regression line during downward tilting (DT-BRS) correlated significantly with Phe-BRS (r = 0.79, p = 0.0003). The DT- and Phe-BRS also correlated significantly with the high frequency component of resting HRV (r = 0.70, p = 0.0023 for DT-BRS; r = 0.58, p = 0.0185 for Phe-BRS). CONCLUSIONS: We conclude that in a small homogeneous group DT-BRS provided an assessment of reflex cardiac vagal function comparable to that obtained by the phenylephrine method.

Adult↗

PubMed1999

Beneficial effects of long-term treatment with enalapril on cardiac function and heart rate variability in patients with old myocardial infarction.

BACKGROUND: The beneficial effects of the early use of angiotensin-converting enzyme inhibitors (ACEis) in patients with acute myocardial infarction (MI) are well documented. However, the effects of ACEis in patients with an old MI and preserved cardiac function have not yet been studied. We examined the effects of 12 months of enalapril treatment in patients with previous MI. METHODS AND RESULTS: Thirteen patients with an old MI and no overt congestive heart failure (CHF), aged 70 +/- 2 years, were treated with enalapril for 12 months. We also included 13 age- and sex-matched control patients who had a similar clinical background but were not treated with enalapril. Holter electrocardiography and echocardiography were performed at entry and after 12 months of treatment. Heart rate variability, low- and high-frequency powers (LF and HF), and the ratio between LF and HF (LF/HF) were analyzed. Changes from baseline to 12 months in HF, LF/HF, left ventricular end-diastolic dimension (LVEDD), and end-systolic dimension (LVESD) were significantly different in the enalapril group (HF, 8.1 +/- 0.9 to 9.3 +/- 0.9 milliseconds: LF/HF, 1.65 +/- 0.11 to 1.53 +/- 0.16; LVEDD, 57.2 +/- 1.6 to 54.7 +/- 1.6 mm; LVESD, 40.0 +/- 2.4 to 36.3 +/- 1.9 mm) compared with the control group (HF, 8.9 +/- 0.9 to 8.5 +/- 0.7 milliseconds; LF/HF, 1.78 +/- 0.18 to 1.88 +/- 0.15; LVEDD, 52.3 +/- 2.5 to 55.9 +/- 2.2 mm; LVESD, 32.5 +/- 2.6 to 36.1 +/- 2.6 mm; P < .05). The delta change (delta) in LVESD between the end and the start of study correlated inversely with deltaHF (r = -0.56; P < .05) and positively with deltaLF/HF (r = 0.65; P < .01). CONCLUSION: Our results suggest possible ongoing structural changes in patients with old MI even in the absence of overt CHF. Enalapril seemed to prevent such changes and to restore cardiac autonomic tone toward normal. Further prospective studies using a larger sample size are warranted to confirm potential beneficial effects of ACEis in patients with previous MI and preserved left ventricular function.

Aged↗

PubMed1999

Probiotic preparations dose-dependently increase net production rates of organic acids and decrease that of ammonia by pig cecal bacteria in batch culture.

We tested probiotic preparations containing Bifidobacterium, Enterococcus, or Lactobacillus to see if they affect production of organic acids and ammonia by mixed cecal bacteria. Four preparations (Bibalance, Neorakuton, Yakult Seichoyaku, or Yakult Seichoyaku BL) were digested with HC and pancreatin before adding to batch cultures of 50% pig cecal contents. Concentrations of organic acids and ammonia in the culture were quantified. Two preparations stimulated the net production of short-chain fatty acids (SCFA) during the first 8 hr of incubation. From 8 to 24 hr of incubation, all preparations accelerated the net production of SCFA, succinic and lactic acids, and three preparations slowed the net production of isovaleric acid and ammonia, all dose-dependently. The above results indicate that the preparations tested accelerated the breakdown of hard-to-degrade carbohydrate(s) and, possibly thereby, decreased the breakdown of proteinous materials or increased bacterial cell body synthesis in a mixed culture of cecal bacteria.

Acetic Acid↗

PubMed1999

Probiotic bacteria stimulate gut epithelial cell proliferation in rat.

Probiotics are used for various intestinal diseases. However, their effects on gut epithelial cell proliferation have not been investigated. We administered 10(7) colony-forming units of Lactobacillus casei or Clostridium butyricum, or no probiotics (control) by gastric intubation once a day for seven days to rats fed an elemental diet. We estimated the crypt cell production rate of the jejunum, ileum, cecum, and distal colon. We also quantified cecal bacteria. Both probiotics increased the crypt cell production rate of the jejunum and ileum by 25-40%, of the cecum by 70%, and of the distal colon by more than 200% compared with control. Only minor variance in the cecal bacterial composition existed among the three groups. Probiotics enhanced gut epithelial cell proliferation in rats fed an elemental diet.

Animals↗

PubMed1999

Induction of rat uncoupling protein-2 gene treated with tumour necrosis factor alpha in vivo.

BACKGROUND: The cytokine tumour necrosis factor (TNF) alpha has been reported to induce metabolic abnormalities such as anorexia and thermogenesis. To investigate functional modulators of uncoupling protein-2 (UCP2) gene expression, we examined the effects of TNF-alpha on UCP2 mRNA expression in rats. METHODS: Mature male Wistar King A (WKA) rats at 10-11 weeks of age were treated with recombinant human TNF-alpha at a dose of 0.6 nmol 100 g-1 body weight by intraperitoneal administration. RESULTS: TNF-alpha treatment induced an increase in UCP2 mRNA expression in broadly distributed tissues including brown adipose tissue (BAT), white adipose tissue (WAT) and skeletal muscle, and an elevation of ob gene mRNA expression in WAT. After the TNF-alpha treatment, an increase in plasma leptin concentration occurred in an ob gene-dependent manner, accompanied by an anorectic effect. CONCLUSION: The present results provide evidence for a new regulatory loop involving TNF-alpha and UCP2, and add novel insights into the regulatory mechanisms of energy homeostasis.

Adipose Tissue↗

PubMed1999

Prostaglandin E2 mediates activation of hypothalamic histamine by interleukin-1beta in rats.

The present study was designed to investigate the effects of peripheral interleukin-1beta (IL-1beta) on hypothalamic histamine (HA) systems. Intraperitoneal injection of IL-1beta increased the turnover rate of hypothalamic HA, which was assessed by accumulation of tele-methylhistamine after pargyline treatment. IL-1beta increased the activities of both histidine decarboxylase (HDC), an HA synthesizing enzyme, and HA-N-methyltransferase (HMT), an HA catabolizing enzyme. Pretreatment with indomethacin completely blocked the effects induced by IL-1beta on hypothalamic HA. Infusion of prostaglandin E2 (PGE2) into the third cerebroventricle increased the hypothalamic HA turnover rate, and simultaneously activated both HDC and HMT dose-dependently, but intravenous infusion of PGE2 had no effect on the dynamics of hypothalamic HA turnover. These results indicate that hypothalamic PGE2 activated by peripheral administration of IL-1beta, but not by peripheral PGE2, may enhance synthesis and release of hypothalamic HA by activation of HDC, and may facilitate degradation of extracellular histamine by activation of HMT.

Animals↗

PubMed1999

QT interval and QT dispersion before and after diet therapy in patients with simple obesity.

To evaluate whether a disordered QT interval and its dispersion in obese patients, if any, may be improved by therapeutic weight reduction, 36 obese patients admitted to our university hospital were examined over a 5-year period from April 1, 1992 to March 31, 1997. Participants included 18 males and 18 females whose mean age +/- SD was 28 +/- 9 and 33 +/- 14 years, respectively, and whose mean body mass index +/- SD was 35 +/- 5 and 38 +/- 6 kg/m2, respectively. Thirty-six control patients were matched in age and gender with the obese patients. All the obese patients were treated with behavioral therapy together with very-low-calorie conventional Japanese diet (VLCD: 370 kcal/day). A standard 12-lead electrocardiogram (ECG) revealed longer maximum (445 +/- 32 msec, mean +/- SD) and minimum (388 +/- 29 msec) heart rate corrected QT intervals (QTc intervals) in the obese group than in the control group (P < 0.0001 for each). QTc dispersion, defined as the difference between maximum and minimum QTc intervals derived from 12-lead ECG, was greater in the obese group (57 +/- 19 msec) than in the control group (32 +/- 13 msec) (P < 0.0001). Both the maximum and minimum QTc intervals in the obese patients were shortened, respectively, to 434 +/- 28 msec and 377 +/- 29 msec (P < 0.05 for each) with no significant change in either QTc dispersion, QRS voltage, or QRS duration following weight reduction. The coefficient value from the linear regression line between QT interval and RR interval in the obese group was less than in the control group. Together, the results show that obesity per se causes both a prolongation of QTc interval and an increase in QTc dispersion, and that weight reduction improves the prolonged QTc interval observed in obese patients.

Adult↗