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Biomedical subjects

S Seto

Publications and source records attributed to S Seto.

At least 37 records · Page 2Linked to original sources
PubMed1999

Chronic Chagas' heart disease in a Japanese-Brazilian traveler. A case report.

A 57-year-old Japanese-Brazilian man, visiting Japan for only 9 days, was admitted to our hospital due to syncope and frequent ventricular premature beats. He grew up in a rural area of Brazil and moved to Sao Paulo in 1959 when he was 20 years old. We suspected chronic Chagas' heart disease, i.e., dilated cardiomyopathy with apical ventricular aneurysm, right bundle branch block with left anterior fascicular block, and various arrhythmias including supraventricular premature beats, ventricular premature beats and non-sustained ventricular tachycardia because he showed typical echo- and electrocardiographic features of the disease. Coronary arteriograms were normal, and left ventriculogram confirmed the existence of apical ventricular aneurysm. A left ventricle biopsy specimen showed hypertrophic cardiac muscle with mild fibrosis. The diagnosis of chronic Chagas' disease was finally confirmed by the demonstration of Trypanosoma cruzi itself in the blood as well as Trypanosoma cruzi antibodies.

Animals↗
PubMed1999

Pretreatment with soluble thrombomodulin prevents intrasinusoidal coagulation and liver dysfunction following extensive hepatectomy in cirrhotic rats.

The major cause of posthepatectomy liver dysfunction is supposed to be microcirculatory disturbance caused by imbalance of intrasinusoidal coagulation equilibrium. Thrombomodulin (TM) is a potent anticoagulant expressed on the endothelial cell surface that regulates the coagulation system by binding thrombin and accelerating the thrombin-catalyzed activation of protein C. Therefore, we examined the effect of soluble TM purified from human urine (UTM) on intrasinusoidal coagulation in cirrhotic rats. Dimethylnitrosamine-induced cirrhotic rats underwent 70% hepatectomy and received endotoxin 48 h after. UTM or vehicle alone was intravenously administered to each rat 30 min before endotoxin injection. UTM treatment attenuated the increases in cytosolic enzymes and serum hyaluronic acid level. The UTM supply improved the survival rate of the rats at 12 h after endotoxin challenge. Histologically, intrasinusoidal fibrin depositions and massive hepatocellular necrosis observed in control rats were scarcely found in UTM-treated rats. Immunohistochemical examination revealed that marked TM stains in sinusoidal endothelial cells were well preserved in UTM-treated rats. In conclusion, UTM administration prevented intrasinusoidal fibrin depositions and attenuated posthepatectomy liver dysfunction in cirrhotic rats.

Animals↗
PubMed1998

The novel cyclopropapyrroloindole(CPI) bisalkylators bearing 3,3'-(1,4-phenylene)diacryloyl group as a linker.

The novel cyclopropapyrroloindole(CPI) bisalkylators were synthesized and their antitumor activity was evaluated. Among these derivatives, AT-760 (5a) in which the two 3-methoxycarbonyl-2-trifluoromethylCPI (MCTFCPI) moieties are connected with a 3,3'-(1,4-phenylene)diacryloyl group, was found to exhibit more prominent cytotoxicity and antitumor activity than U-77,779 (bizelesin) (1).

Adenocarcinoma↗
PubMed1998

Hepatocyte growth factor promotes liver regeneration with prompt improvement of hyperbilirubinemia in hepatectomized cholestatic rats.

BACKGROUND: In hepatectomy for patients with liver cirrhosis or cholestasis, prolonged postoperative hyperbilirubinemia is a troublesome complication and, if uncontrolled, often leads to life-threatening hepatic failure. Hepatocyte growth factor (HGF), first identified as the most potent mitogen for primary hepatocytes, has been shown to have multiple biological properties on liver, including mitogenic, antifibrotic, and cytoprotective activities. This study investigated the beneficial effects of a perioperative HGF supply to jaundiced liver after hepatectomy in rats. MATERIALS AND METHODS: As a model of jaundiced liver, we used an alpha-naphtylisocyocyanate (ANIT)-induced intrahepatic cholestasis model. Forty-eight hours after intraperitoneal injection of ANIT (75 mg/kg), when the total serum bilirubin level was moderately increased, a 70 % hepatectomy was performed. Human recombinant HGF (250 microgram/kg) (n = 15) or vehicle alone (n = 15) was intermittently administered to the rats 12 h before surgery and every 12 h after that until sacrifice. RESULTS: Perioperative HGF treatment effectively accelerated hepatocellular DNA synthesis of cholestatic liver followed by increase in the regenerated liver weight. Moreover, HGF supply promptly improved hyperbilirubinemia within 24 h after surgery. Histological examination revealed that HGF administration attenuated periportal inflammation and formation of bile duct obstructions. Postoperative serum concentrations of tumor necrosis factor-alpha, a representative inflammatory cytokine, were not altered by HGF treatment. CONCLUSIONS: Perioperative HGF supply not only promotes liver regeneration but also ameliorates hyperbilirubinemia in hepatectomized cholestatic rats. This mode of HGF treatment may be clinically useful for hepatectomy in patients with cholestasis.

Animals↗
PubMed1998

Central pressor effect of parathyroid hormone-related protein in conscious rats.

Although the parathyroid hormone-related protein gene is widely expressed in the central nervous system, the role of this protein in blood pressure is unknown. This article examines whether parathyroid hormone-related protein is involved in the central regulation of blood pressure. An intraventricularly injected solution of parathyroid hormone-related protein elicited a dose-dependent increase of mean arterial pressure accompanied by a decrease of heart rate in conscious Sprague-Dawley rats. An anti-parathyroid hormone-related protein monoclonal antibody, given in an intraventricularly injected solution, blocked the pressor effect of parathyroid hormone-related protein. Furthermore, this pressor effect of parathyroid hormone-related protein was also abolished after pretreatment by intravenous administration of either hexamethonium bromide or doxazosin mesylate. These results suggest that central parathyroid hormone-related protein is implicated in the regulation of blood pressure, and that this effect may be mediated through sympathetic activation.

Analysis of Variance↗
PubMed1998

Perioperative continuous hepatocyte growth factor supply prevents postoperative liver failure in rats with liver cirrhosis.

Insufficient regeneration and dysfunction of cirrhotic liver following partial hepatectomy often make the resection extremely vulnerable to postoperative liver failure, which frequently leads to multiple organ failure. Hepatocyte growth factor (HGF), first identified as the most potent mitogen for primary hepatocytes, not only stimulates hepatic regeneration but also accelerates liver function, improves fibrosis, and protects liver cells against injury. Therefore, we investigated the ability of a continuous supply of HGF to cirrhotic livers to prevent postoperative liver failure in rats. After liver cirrhosis was induced in 40 rats by the intraperitoneal injection of dimethylnitrosamine (DMN) for 4 weeks, fibroblasts genetically modified to secret rat HGF or control fibroblasts were implanted in the spleens of 20 syngenic rats per group to supply HGF continuously and directly to the cirrhotic livers. Two weeks after the implantation, all rats underwent a 30% hepatectomy. The HGF administration significantly improved liver fibrosis at the time of operation, attenuated the postoperative hepatic damage on histological examination, markedly accelerated the liver regeneration at 24 h after the hepatectomy. The blood chemical analysis indicated that HGF significantly suppressed postoperative liver failure. Most importantly, the HGF treatment significantly improved the survival rate of the rats at 48 h after the hepatectomy. The perioperative continuous supply of HGF from the spleen effectively prevented liver failure following resection of cirrhotic livers in rats.

Animals↗
PubMed1998

Portal branch ligation with a continuous hepatocyte growth factor supply makes extensive hepatectomy possible in cirrhotic rats.

In a cirrhotic liver, the regenerative ability and specific functions are so impaired that excessive resection easily complicates postoperative liver dysfunction, which frequently leads to life-threatening multiple-organ failure. Hepatocyte growth factor (HGF), first identified as the most potent stimulator of DNA synthesis in primary hepatocytes, not only stimulates liver regeneration, but also accelerates hepatic function, improves fibrosis, and protects liver cells against injury. Therefore, we investigated the efficacy of preoperative portal branch ligation (PBL) (which can induce compensatory hypertrophy of the unaffected lobes) combined with a continuous HGF supply in the performance of extensive hepatectomy in cirrhotic rats. Cirrhosis was induced by intraperitoneal injections of dimethylnitrosamine (DMN) three times per week for 3 weeks. Five days after the last injection, when 70% hepatectomy is lethal, the rats underwent portal ligation of the left lateral and median branches (corresponding to approximately 70% of the total volume of the liver). Simultaneously, they were continuously treated with either recombinant human HGF (rhHGF) or vehicle from an intraperitoneally implanted osmotic pump. Four days after the portal ligation, the occluded lobes were resected. The HGF treatment rapidly increased both the wet weight of the unoccluded lobes and the hepatocellular DNA synthesis. The blood chemical analysis indicated that HGF significantly suppressed the posthepatectomy liver dysfunction. Most importantly, the HGF treatment markedly improved the survival rate of the rats at 48 hours after the major hepatectomy. In conclusion, PBL combined with a continuous HGF supply makes extensive hepatectomy possible in cirrhotic rats, mainly by promoting the hypertrophy of the unaffected lobes.

Animals↗
PubMed1998

Coronary risk factors in acute Kawasaki disease: correlation of serum immunoglobulin levels with coronary complications.

BACKGROUND: To determine the usefulness of the IgG z-score (age and sex-standardized serum IgG level) before intravenous gamma globulin therapy (IVGG) in predicting the occurrence or severity of coronary complications in Kawasaki disease (KD). METHODS: A case-control study of clinical and laboratory findings with 88 children in the early stage of acute KD who received IVGG (100 or 200 mg/kg for 2-5 days) therapy. Of these, 20 cases had persistent coronary arterial lesions (small aneurysm, moderate aneurysm or large aneurysm persisting more than 1 month). The controls comprised 68 children with no coronary aneurysms or transient small aneurysm only observed within 1 month after the onset of KD. The association between serum levels of immunoglobulin G (IgG). IgM, IgA as well as other coronary risk factors previously reported and the occurrence of the coronary arterial lesions was evaluated using logistic regression analysis. RESULTS: After adjustment for age, gender, total IVGG dose before the 9th illness day and other traditional coronary risk factors, the odds ratio for the persistent coronary aneurysm associated with lower serum IgG z-score (< -0.7485 vs > or = -0.7485), was 30.3 (95% confidence interval, 3.8-243.2). Furthermore, the serum IgG z-score was inversely correlated with the severity of the coronary arterial lesion. CONCLUSIONS: The IgG z-score before IVGG therapy in the early stage of KD provides useful information on the risk factors for persistent coronary aneurysm and is a novel, additional indicator for therapy to prevent the coronary complications in acute KD.

Case-Control Studies↗
PubMed1998

Cell reproduction and morphological changes in Mycoplasma capricolum.

The cell reproduction of Mycoplasma capricolum was studied. The velocity of DNA replication fork progression was about 6 kb/min, which is 10 times slower than that of Escherichia coli. The time required for one round of DNA replication accorded with the doubling time. The origin/terminus ratio was 2.0. M. capricolum cell morphology was classified into two types, rod and branched. In the ordinary-growth phase, the rod cells accounted for about 90% of the total population, with branched cells comprising the remaining 10%. The proportion of branched cells increased to 90% following inhibition of DNA replication by nucleoside starvation. An increase in the proportion of branched cells was induced by transfer of a temperature-sensitive mutant deficient in DNA replication to the restrictive temperature. The rod cells had a regular structure, a fixed cell length, and constrictions in the center. The DNA contents of individual rod cells were distributed with a standard deviation of 0.40 of average. The branched cells had irregular structures and a wide distribution of DNA contents. Counting of viable cells revealed that the cells ceased division upon cell type conversion; however, branched cells maintained a reproductive capacity. A model for the reproduction process is proposed.

Bacterial Proteins↗
PubMed1998

Influence of mild to moderate obesity on left ventricular stress filling pattern in hypertension.

In resting condition, obese subjects are described as having impaired diastolic filling. To examine the effect of mild to moderate obesity on left ventricular diastolic performance during stress in hypertension, we determined the filling responses to dynamic submaximal exercise in 19 obese hypertensive patients (body mass index, 26 to 30 kg/m2) with a normal left ventricular structure, 19 age- and sex-matched, non-obese hypertensive patients, and 19 age- and sex-matched, non-obese normotensive controls (mean age, 55+/-3 yr). Doppler echocardiographic studies were performed at baseline and 1 min after exercise on a supine ergometer bicycle. At rest, systolic function and filling indices, peak velocities of early (E) and late (A) filling, and their ratio (E/A), were similar in the two hypertensive groups, while normotensive controls had higher peak velocities of E and E/A. At a maximum workload of 75 W, blood pressure and heart rate increased similarly in the two hypertensive groups. Peak velocities of E and A increased significantly after exercise. The percentage change in the peak velocity of E was greater in obese hypertensive patients than in non-obese hypertensive patients and normotensive controls (23+/-4 vs. 12+/-3 and 14+/-3%, p < 0.05). Percentage changes in A and E/A were similar in the three groups. Our study suggests that mild to moderate obesity does not further worsen left ventricular diastolic filling at rest and mitigates diastolic filling abnormalities after exercise in hypertensive patients.

Blood Flow Velocity↗
PubMed1997

Continuous hepatocyte growth factor supply prevents lipopolysaccharide-induced liver injury in rats.

We present a rat model in which continuous supply of hepatocyte growth factor (HGF) prevents liver injury induced by carbon tetrachloride (CCl4) and E. coli 011:B4 lipopolysaccharide (LPS). Rat fibroblasts genetically modified to secrete rat HGF were implanted in syngenic rat spleen 7 days before administration of the hepatotoxins. Rats with HGF-secreting fibroblasts in the spleen showed a dramatic resistance to CCl4- and LPS-induced liver injury. In the LPS-induced liver injury model, blood chemical analysis revealed that the increase in serum glutamic oxalacetic transaminase level and the decrease in blood sugar level were remarkably suppressed in rats with HGF-secreting cells in the spleen. Most importantly, their survival rate was greatly improved compared to other control groups of rats. Thus our results indicate a new role of HGF in liver protection during endotoxemia and convey important clinical implications for developing new therapeutic modalities in the treatment of liver failure caused by endotoxemia.

Alanine Transaminase↗
PubMed1997

Characterization of dnaA gene expression in Mycoplasma capricolum.

Expression of the dnaA gene in Mycoplasma capricolum was studied. The transcriptional start site was located 10 bp upstream from the putative translational initiation codon. Immunoblotting analysis revealed that DnaA protein was expressed at the levels significantly larger than those in Escherichia coli, and was localized mainly in the membrane. The transcriptional level of dnaA gene was reduced by inhibition of DNA synthesis with methyl methanesulfonate or mitomycin C, while the level of DnaA protein did not change. Reduction of protein synthesis did not significantly affect the total amount of DnaA protein, suggesting that the rates of synthesis and degradation of the protein are slow. These observations showed that the expression pattern of dnaA gene in M. capricolum is different from those of walled bacteria in some aspects.

Amino Acid Sequence↗
PubMed1997

Evidence of three clinical subgroups in patients with dual atrioventricular nodal pathways.

We attempted to test the hypothesis that dual atrioventricular (A-V) nodal pathways with second-degree atrioventricular block (2nd A-V block) present as a different clinical entity from those with A-V nodal reentranttachycardia (AVNRT). By evaluation with Holter monitoring (2.9 +/- 2.5 recordings/patient) and 12-lead electrocardiogram (11.9 +/- 11.6), 177 patients with dual A-V nodal pathways could be divided into three subgroups. Thirty-two patients had 2nd A-V block only (2nd A-V block group), 57 had AVNRT only (AVNRT group), 88 had neither 2nd A-V block nor AVNRT (silent group), and none had 2nd A-V block and AVNRT both. Electrophysiologic studies showed that the atrio-His interval was significantly greater (P < 0.0001) and the maximal 1:1 atrioventricular conduction rate was lower (P < 0.0001) in the 2nd A-V block group than in the other two groups. These differences were nullified after the administration of atropine. These results suggest that patients with dual A-V nodal pathways can be classified into three clinical subgroups based on the presence of either 2nd A-V block or AVNRT. We suggest also that patients of the 2nd A-V block group may have a more augmented vagal tone on the A-V node than the other two groups.

Adolescent↗
PubMed1997

Centrally administered calcium increases the maximum vagal activation of baroreceptor reflex control of heart rate in spontaneously hypertensive rats.

Baroreceptor reflex control of heart rate (HR) was examined before and 15 min after intracerebroventricular infusion (i.c.v.) of 10 microliters of high-Ca2+ solution (Ca2+, 16.3 mM) in conscious spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY). The slope of the individual regression line of the relation between reflex HR changes (delta HR) and changes in mean arterial pressure (delta MAP) produced by bolus injections of phenylephrine or sodium nitroprusside (delta HR/delta MAP; beats/min/ mm Hg) for bradycardia was significantly less in SHR (-0.60 +/- 0.30; n = 10) than in WKY (-1.78 +/- 0.27; n = 10; p < 0.01) at baseline. The slope increased in SHR during administration of high Ca2+ to -1.39 +/- 0.17 (p < 0.01) but not in WKY: In contrast, no significant changes were observed for the reflex tachycardia both in SHR (n = 7) and WKY (n = 10). Further, we analyzed sigmoidal MAP-HR reflex curves in SHR with i.c.v. of either high Ca2+ (n = 6) or artificial cerebrospinal fluid (aCSF; n = 5). Administration of high Ca2+ reduced the bradycardic plateau and increased HR range without changes in average gain. Our results suggest a modulatory role for central Ca2+ in the baroreceptor reflex control of HR in SHR.

Animals↗
PubMed1997

Enhanced depressor effect of centrally administered high-calcium solution in salt-loaded experimental hypertension.

The depressor effect by oral calcium supplementation is known to be more pronounced in salt-dependent than in renin-dependent hypertension. This study was conducted to investigate the role of central calcium on two different pathophysiologic subtypes of experimental hypertension; (a) salt-dependent, deoxycorticosterone acetate-salt hypertensive rats (DOCA), and (b) renin-dependent, 2-kidney, 1 clip (2-K, 1C) hypertensive rats. In DOCA (n = 10), high-calcium solution (Ca+2, 65.2 mM, 10 microl) given centrally (i.c.v.) elicited a marked decrease in mean blood pressure (MBP; 170 +/- 4 to 138 +/- 5 mm Hg, p < 0.01) with a decrease in heart rate (HR; 390 +/- 18 to 344 +/- 17 beats/min, p < 0.05) lasting for 40 min. In 2-K, 1C (n = 10), high-Ca2+ i.c.v. showed a lesser decrease in MBP (178 +/- 4 to 171 +/- 5 mm Hg) and HR (419 +/- 10 to 395 +/- 12 beats/min) with shorter duration (for 20 min) than in DOCA. This significant depressor and bradycardic response to Ca2+ i.c.v. observed in DOCA was dose dependent at Ca2+ concentrations between 65.2 and 130.4 mM. In DOCA, high Ca2+ i.c.v. reduced the plasma noradrenaline (Nad) concentration significantly (479 +/- 81 to 319 +/- 62 pg/ml, p < 0.05). These results suggest that central Ca2+ plays a more important role in regulating sympathetic nerve activity and BP in salt-dependent than in renin-dependent experimental hypertension.

Animals↗
PubMed1997

Emergence of radial nerve dominance in median nerve cortex after median nerve transection in an adult squirrel monkey.

Throughout the glabrous representation in Area 3b, electrical stimulation of the dominant (median or ulnar) input produces robust, short-latency excitation, evident as a net extracellular "sink" in the Lamina 4 current source density (CSD) accompanied by action potentials. Stimulation of the collocated nondominant (radial nerve) input produces a subtle short-latency response in the Lamina 4 CSD unaccompanied by action potentials and followed by a clear excitatory response 12-15 ms later. Laminar response profiles for both inputs have a "feedforward" pattern, with initial activation in Lamina 4, followed by extragranular laminae. Such corepresentation of nondominant radial nerve inputs with the dominant (median or ulnar nerve) inputs in the glabrous hand surface representation provides a likely mechanism for reorganization after median nerve section in adult primates. To investigate this, we conducted repeated recordings using an implanted linear multi-electrode array straddling the cortical laminae at a site in "median nerve cortex" (i.e., at a site with a cutaneous receptive field on the volar surface of D2 and thus with its dominant afferent input conveyed by the median nerve) in an adult squirrel monkey. We characterized the baseline responses to median, radial, and ulnar nerve stimulation. We then cut the median nerve and semichronically monitored radial nerve, ulnar nerve and median nerve (proximal stump) evoked responses. The radial nerve response in median nerve cortex changed progressively during the weeks after median nerve transection, ultimately assuming the characteristics of the dominant nerve profile. During this time, median, and ulnar nerve profiles displayed little or no change.

Action Potentials↗
PubMed1996

Correlation between systolic blood pressure and physical development in adolescence.

Although the close relation between blood pressure and physical development in adolescence has been established in cross-sectional and comparative cross-sectional studies, the entire trend of systolic blood pressure (SBP) during adolescence has not been elucidated in conjunction with physical development in a longitudinal study. Blood pressure (mmHg), body weight (kg), and body height (m) were measured annually for 418 subjects in Hiroshima and Nagasaki, Japan, from age 10 (1955 or 1956) through 18 years (1963 or 1964). The Gompertz growth model was used to determine the velocity of weight increase (VEL) during that age period. The relations between SBP from age 10 to 18 and VEL, weight, height, body mass index (BMI; weight/height2, kg/m2), and the age at which the measurements were made were investigated individually using random-coefficient growth-curve analysis. The SBP trend for the 10- to 18-year age period could be shown by the following prediction equations: for the 163 Hiroshima males, SBP = 82.38 + 0.89 VEL at age 1.15 years prior to the current examination (VEL (age - 1.15)) + 1.40 BMI; for the 57 Nagasaki males, SBP = 92.70 + 1.07 VEL (age - 1.15) + 0.79 BMI; for the 148 Hiroshima females, SBP = 104.88 + 1.63 VEL (age - 1.15) + 0.05 BMI; for the 50 Nagasaki females, SBP = 113.62 + 1.67 VEL (age - 1.15) - 0.59 BMI. VEL 1.15 years prior to the current examination was significantly and positively related to SBP in each city by sex group (p < 0.01), and current BMI was significantly related to SBP for males in Hiroshima (p < 0.01) and nearly so in Nagasaki (p = 0.06), but not for females in either city (p = 0.84 and 0.13, respectively). Because the plot of VEL was a convex curve, SBP peaked approximately 1-2 years after the peak in VEL and then decreased in both sexes. The entire SBP trend during adolescence can be expressed as an equation of VEL and BMI in males and of VEL in females. SBP does not increase linearly with age.

Adolescent↗