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Biomedical subjects

J Hasegawa

Publications and source records attributed to J Hasegawa.

At least 19 recordsLinked to original sources

Laparoscopically assisted total gastrectomy with jejunal pouch interposition.

BACKGROUND: Jejunal pouch interposition (JPI) is known as a useful gastric replacement procedure after total gastrectomy. The JPI procedure, however, has not been applicable to laparoscopically assisted total gastrectomy (LATG) because of its technical complexity and difficulty. This study aimed to describe our modified LATG/JPI technique, and to evaluate its feasibility, safety, and early postoperative functional outcome. METHODS: Between September 2002 and August 2003, LATG/JPI was attempted for five patients (3 men and 2 women) with early gastric cancers in the upper portion of the stomach. The mean age of the patients was 57 years, and their BMI was 21 kg/m2. Using a 5-port technique, the gastric arteries were laparoscopically clipped and divided with adequate lymphatic dissection. After completion of gastric resection, the anvil of a circular stapling device was placed in the esophageal stump. An 8-cm minilaparotomy then was performed, and the 12-cm pouch was created extracorporeally in the "reverse U" fashion. The stapled pouch-esophagostomy was performed under laparoscopic monitoring. The remainder of the procedure was accomplished under direct vision. RESULTS: All cases were managed laparoscopically without any complications. The mean operating time was 407 min, and the blood loss was 279 ml. All the patients showed rapid and uneventful recovery. Postoperative studies, including dual scintigraphy, showed that all jejunal pouches were satisfactorily functioning. CONCLUSIONS: This study showed LATG/JPI to be feasible and safe. With technical modifications, LATG/JPI can become a potentially effective option for improving patients' quality of life after total gastrectomy.

Feasibility Studies↗

Velamentous cord insertion into the lower third of the uterus is associated with intrapartum fetal heart rate abnormalities.

OBJECTIVES: To evaluate the accuracy of sonographic identification of the site of umbilical cord insertion (CI) at 18-20 weeks of gestation, to compare the sensitivities for detection of a velamentous cord insertion (VCI) secondary to a CI into the anterior, posterior or fundal wall, and to compare the intrapartum complications secondary to VCI into the upper, middle or lower third of the uterus. METHODS: As part of the routine ultrasound scan at 18-20 weeks' gestation we evaluated abnormal CI (VCI and marginal CI) and the location of the CI in the uterus in 3446 pregnancies. In cases of abnormal CI, the location of the CI was further classified as being in the upper, middle or lower third of the uterus. After delivery, the placenta and the umbilical cord were examined and intrapartum complications were compared with the location of the CI. RESULTS: The values for antenatal detection of VCI were: sensitivity, 25 of 40 (62.5%); positive predictive value, 25 of 25 (100%); and negative predictive value, 3406 of 3421 (99.6%). The sensitivity for cases in which the CI was located on the anterior wall was 12 of 13 (92.3%); when it was located on the posterior wall, the sensitivity was 11 of 22 (50.0%); and when it was fundal the sensitivity was 2 of 5 (40.0%). Variable decelerations were frequently observed with a VCI. In lower VCI cases, non-reassuring fetal heart rate patterns and emergency Cesarean sections occurred with a higher frequency than in cases with upper or middle VCI (P < 0.01). After delivery, the length of the aberrant vessels in cases of VCI by pathologic examination was 3.9 +/- 3.3 cm in the upper third, 4.7 +/- 4.6 cm in the middle third, and 10.6 +/- 6.8 cm in the lower third; thus, the aberrant vessel length was significantly greater when the CI was in the lower third of the uterus (P = 0.024). CONCLUSION: We have demonstrated that VCI with a lower CI site and with longer aberrant vessels is associated with various intrapartum complications. This finding has the potential for improving perinatal outcome.

Female↗

Cord insertion into the lower third of the uterus in the first trimester is associated with placental and umbilical cord abnormalities.

OBJECTIVES: To assess the feasibility of detecting the cord insertion site during the late first trimester, and to investigate the possible association between perinatal complications and a cord insertion in the lower third of the uterus in the first trimester. METHODS: This was a prospective cohort study in which the positional relationship between the uterus and the cord insertion site was examined using gray-scale transvaginal sonography at 9-11 weeks of gestation. The distance between the internal os and the fundus was divided equally into three parts. Cord insertions located in the upper or middle thirds were defined as normal (controls), and those located in the lower third were defined as cases, regardless of their relationship to the chorion villosum. Third-trimester sonography and pathological examination of the placenta and cord at delivery were performed to check for placental/cord abnormalities. The univariate association between the location of the cord insertion in the first trimester and placental and umbilical cord abnormalities and perinatal complications was assessed. RESULTS: The cord insertion site was identified in 318/340 (93.5%) cases at 9-11 weeks of gestation and it was in the lower third of the uterus in 35 (11.0%) cases. Of these 35, the cord insertion was found at delivery to be low in nine cases (26%) and the placenta was low-lying at delivery in eight (23%). None of the 283 cases with a normal cord insertion in the first trimester was found to have a low-lying placenta at delivery (P < 0.0001). Ten (29%) of the cases with a low cord insertion and four (1.4%) with a normal cord insertion in the first trimester had a velamentous or marginal cord insertion at delivery (P < 0.0001). At delivery, five (14%) of the low cord insertion cases and four (1.4%) of the normal cord insertion cases (P < 0.0001) had some form of placental malformation, including accessory placenta and infarction of the placenta. An emergency Cesarean section was performed in four (11%) and six (2.1%) of the low and normal cord insertion cases, respectively (P = 0.003). CONCLUSION: Developmental abnormalities of the placenta and umbilical cord occur frequently in cases in which the cord insertion is in the lower third of the uterus in the first trimester. We suggest that screening for the cord insertion site at 9-11 weeks of gestation may have clinical significance for predicting abnormalities of the cord and the placenta at delivery.

Adult↗

Mass balance study of [14C] rabeprazole following oral administration in healthy subjects.

The study was designed to determine the excretion balance of radiolabeled rabeprazole in urine and feces and to examine the metabolite profile in plasma, urine and feces after a single oral dose of [14C] rabeprazole, preceded by once daily dose of rabeprazole for 7 days. Six healthy subjects were enrolled in this study. The study was a single-center, open-label, multiple-dose, mass-balance study. Each subject received a single 20 mg dose of rabeprazole tablet for 7 days followed by the administration of 20 mg of [14C] rabeprazole as an oral solution after an overnight fast on Day 8. After oral dosing of [14C] rabeprazole, the mean Cmax of total radioactivity was 1,080 +/- 215 ng equivalent/ml with 0.33 +/- 0.13 hours of the mean tmax. The apparent elimination half-life of total [14C] radioactivity was 12.6 +/- 3.4 hours. The total [14C] recovery in urine and feces was 99.8 +/-0.7% by 168 hours after oral administration of [14C] rabeprazole, and mean cumulative [14C] radioactivity excreted in urine was 90.0 +/- 1.7% by 168 hours and 79.8 +/- 2.5% of the radioactivity was excreted in urine within 24 hours. Excretion via feces added to the total by 9.8%. The major radioactive component in the early plasma samples was rabeprazole, however the thioether and thioether carboxylic acid metabolites were the main radioactive components in the later plasma sample. These results support the previous finding that the substantial contribution of the non-enzymatic thioether pathway minimizes the effect of CYP2C19 polymorphism on the inter-individual variation ofplasma clearance of rabeprazole compared with other PPIs. Low levels of the sulfone metabolite were detected only in early plasma samples. No rabeprazole was detected in any urine and feces samples. The main radioactive components in urine were thioether carboxylic acid and mercapturic acid conjugate metabolites, and in the feces, the thioether carboxylic acid metabolite. The administration of [14C] rabeprazole was safe as evidenced by the lack of serious adverse events and the fact that all observed events were mild in intensity. [14C] rabeprazole was rapidly absorbed after oral administration and mostly excreted in urine.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Microbial synthesis of chiral amines by (R)-specific transamination with Arthrobacter sp. KNK168.

Arthrobacter sp. KNK168 shows (R)-enantioselective transaminase [(R)-transaminase] activity, which converts prochiral ketones into the corresponding chiral (R)-amines in the presence of an amino donor. The cultural conditions and reaction conditions for asymmetric synthesis of chiral amines with this microorganism were examined. The transaminase was inducible, and its production was enhanced by the addition of sec-butylamine and 3-amino-2,2-dimethylbutane to the culture medium. (R)-1-Phenylethylamine was a good amino donor for amination of 3,4-dimethoxyphenylacetone with Arthrobacter sp. KNK168. Under the optimum conditions, 126 mM (R)-3,4-dimethoxyamphetamine (DMA) [>99% enantiomeric excess (ee)] was synthesized from 154 mM 3,4-dimethoxyphenylacetone and 154 mM (R)-1-phenylethylamine through the whole cell reaction with an 82% conversion yield. (R)-Enantiomers of other amines, such as (R)-4-methoxyamphetamine, (R)-1-(3-hydroxyphenyl)ethylamine and (R)-1-(3-hydroxyphenyl)ethylamine, were also synthesized from the corresponding carbonyl compounds through asymmetric amination with Arthrobacter sp. KNK168.

Acetone↗

Velamentous cord insertion and atypical variable decelerations with no accelerations.

OBJECTIVES: To examine intrapartum fetal heart rate (FHR) patterns in the presence of velamentous cord insertion (VCI). METHODS: The site of cord insertion was determined in 1460 women on antenatal ultrasonographic and postnatal examinations. Each of 24 women with pregnancies complicated with VCI was matched at the onset of labor with 10 women who had a normal pregnancy, and FHR patterns were analyzed for both cases and controls. RESULTS: Compared with controls, cases of variable decelerations with no accelerations (VDNA) during the first and second stages of labor were more frequent in women with VCI (first stage: 25% vs. 5.1%, second stage: 65.0% vs. 21.7%, P < 0.001). The adjusted odds ratio associated with VDNA occurrence in women with VCI was 3.83 (95% confidence interval [CI]: 1.51-9.72, P = 0.005). The mean odds ratio associated with length of aberrant vessels in women with VCI plus VDNA was 1.38 (95% CI: 1.04-1.83, P = 0.026). CONCLUSION: Pregnancies complicated with VCI are associated with a higher rate of VDNA.

Adult↗

Pharmacokinetics of rabeprazole following single intravenous and oral administration to healthy subjects.

The study was designed to determine the absolute bioavailability of 20 mg rabeprazole tablets in normal, healthy subjects in comparison with intravenous administration of 20 mg rabeprazole. Twenty-eight healthy subjects were enrolled in this study. The study was a randomized, balanced, open-label, 2-period crossover study. Each subject was randomized at the beginning of the study to receive either a single 20 mg dose of rabeprazole intravenously or orally during Period 1. Following a 7-day washout period, all subjects received the alternate formulation during Period 2. Intravenous dose was given in constant infusion over five minutes. The absolute bioavailability of rabeprazole was 51.8%. The elimination half-life of rabeprazole sodium (1.47 +/- 0.82 h) after oral administration was significantly longer than the elimination half-life after intravenous administration (1.02 +/- 0.63 h), probably due to slower rate of absorption than that of elimination. The mean total body clearance was 283 +/- 98 ml/minutes following a 20 mg intravenous dose. The administration of rabeprazole sodium was safe as evidenced by the lack of serious adverse events and the rapid resolution of the mostly mild adverse events that occurred during the study. Both treatments were well-tolerated throughout the study. Rabeprazole was well-absorbed after oral administration.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Novel bioreduction system for the production of chiral alcohols.

Chiral alcohols are useful intermediates for many pharmaceuticals and chemicals. Enzymatic asymmetric reduction of prochiral carbonyl compounds is a promising method for producing chiral alcohols. There have been many attempts to construct bioreduction systems for the industrial production of chiral alcohols. This review focuses on the establishment of a novel bioreduction system using an Escherichia coli transformant co-expressing genes for carbonyl reductase and cofactor-regeneration enzyme. This bioreduction system could be useful as an all-purpose catalyst for asymmetric reduction reactions.

Alcohol Oxidoreductases↗

Sensitive detection of human telomerase reverse transcriptase mRNA in the serum of patients with hepatocellular carcinoma.

BACKGROUND/AIM: Telomerase reverse transcriptase protein (hTERT) mRNA has been reported to be detectable by reverse transcription polymerase chain reaction (RT-PCR) in the serum of patients with breast cancer. We measured serum hTERT mRNA in patients with hepatocellular carcinoma (HCC), and examined its clinical usefulness. METHODS: We performed RT-PCR to detect the expression of hTERT mRNA in 78 patients with HCC, 10 with liver cirrhosis (LC), 12 with chronic hepatitis (CH), and 34 healthy individuals without any liver diseases and cancers, and statistically analyzed the association with clinical parameters which include age, sex, etiology, Child classification, underlying liver disease, biochemical data, alpha-fetoprotein (alpha-AFP) number and size of tumor, and histological differentiation of HCC regarding HCC patients. RESULTS: 70 of 78 (89.7%) patients with HCC, 7 of 10 (70.0%) with LC, and 5 of 12 (41.7%) with CH were positive for hTERT expression, whereas all healthy individuals were negative for it. A multivariate analysis showed that positivity of hTERT mRNA was independently associated with AFP, tumor size, and differentiation degree. CONCLUSIONS: These results suggest that this assay is sensitive enough to detect hTERT mRNA in serum, and that it would be applicable for early detection and diagnosis of HCC or other cancers by a quantitative method.

Aged↗

Effects of long-term administration of sulindac on APC mRNA and apoptosis in colons of rats treated with azoxymethane.

PURPOSE: Non-steroidal anti-inflammatory drugs, including sulindac, have been shown to exhibit anti-colon cancer activity; however, the detailed mechanisms concerning continuous long-term administration are still unclear. Therefore, we examined the anti-colon carcinogenesis effects of sulindac after prolonged administration. METHODS: Administration of AOM, a colon-specific carcinogen, induced colonic preneoplastic lesions, which can progress to carcinomas about 40-50 weeks after AOM administration. We studied the effects of sulindac on the incidence of preneoplastic lesions, proliferative activity of colonic cells (AgNORs), tumor suppressor adenomatous polyposis coli (APC) gene expression, and apoptosis using AOM-treated rat colon mucosa at 4 weeks and 40 weeks (early and late stage of colon carcinogenesis, respectively). RESULTS: Sulindac suppressed the development of preneoplastic lesions induced by AOM at 4 weeks and 40 weeks by about 50% ( P<0.01); the proliferative activity of colonic cells increased by AOM was suppressed almost completely. Furthermore, APC expression was significantly increased by sulindac at both the early and late stages ( P<0.01). However, apoptosis was clearly increased at the early stage ( P<0.01), but not at the late stage. CONCLUSIONS: APC overexpression induced by sulindac can suppress colon carcinogenesis at both the early and late stages, but apoptosis might work as one of anti-cancer mechanisms at the early stage of colon carcinogenesis.

Adenomatous Polyposis Coli Protein↗

Molecular changes in the early stage of colon carcinogenesis in rats treated with azoxymethane.

To elucidate early molecular events related to colon carcinogenesis, we examined alterations in the expression of colon cancer-related genes such as cyclooxygenase (COX)-2, APC and c-Myc, cell proliferation and apoptosis in the background colon mucosa, and K-ras mutation at aberrant crypt foci (ACF) in the colons of azoxymethane (AOM)-treated rats 4 weeks after the first exposure to AOM. About 40 ACF/colon were induced in the colons of rats treated with AOM (Group 1); however, rats not treated with AOM (Group 2) showed no ACF formation in the colon. The level of AgNORs in the colonic mucosa was significantly higher in Group 1 than in Group 2 (P<0.01). The colonic mucosa in Group 1 looked macroscopically and histologically normal, but the proliferative activity of the mucosa of rats treated with AOM was clearly elevated. COX-2 mRNA expression was not detected in normal colonic mucosa in Group 2, but 3 out of 10 rats in Group 1 showed COX-2 mRNA expression in their colons by reverse transcription (RT)-polymerase chain reaction (PCR). There was a tendency toward an increased expression level of COX-2 in the AOM-treated group. The level of APC mRNA expression in Group 1 was significantly lower than that in Group 2 (P<0.01). Moreover, the level of c-Myc mRNA expression in Group 1 was significantly higher than that in Group 2 (P<0.01). An average of 0.034+/-0.006% apoptosis in colonic mucosa was detected in Group 1; the incidence of apoptosis in Group 2 was 0.021+/-0.005%. The difference between Groups 1 and 2 was significant (P<0.01). These results indicate that apoptosis was possibly induced to eliminate cells damaged by AOM administration. Six out of 22 (27%) ACF with 4 or more crypts showed K-ras mutations at codon 12; all mutations were G to A transitions (GGT to GAT). ACF with 1-3 crypts showed no mutations in the K-ras gene. In conclusion, AOM caused an increase in COX-2 and c-Myc mRNA expression, a decrease in APC mRNA expression, induction of apoptosis in normal-appearing colonic mucosa, and a K-ras mutation in ACF with 4 or more crypts. These findings may help to identify key targets in the early steps of colon carcinogenesis, against which drugs that would be broadly effective for chemoprevention of colon cancer could be developed.

Adenomatous Polyposis Coli Protein↗

hTR repressor-related gene on human chromosome 10p15.1.

Somatic cells express genes that suppress telomerase activity and these genes may be inactivated in tumour cells. We postulated that cancer cells acquire immortality by activation of telomerase by the loss of such a gene. We have reported recently that a telomerase repressor gene may be located on 10p15.1 by deletion mapping using microcell-mediated chromosome transfer (MMCT), radiated microcell fusion (RMF), fluorescent in situ hybridization (FISH) and STS analysis. To independently confirm this result, we correlated expression of RNA component of telomerase (hTR) as a marker of telomerase expression by in situ hybridization with allelic loss in pulmonary carcinoid tumours. Unlike most malignant tumours, pulmonary carcinoids (which are low-grade malignant tumours) are heterogeneous for telomerase expression. Loss of 5 closely spaced polymorphic markers on 10p15.1, especially D10S1728, were highly correlated with hTR expression. In an additional experiment, 10p15.1 showed higher and more significant correlation than any region of 3p where it has been predicted as another chromosomal location of telomerase repressor with allelic loss of the region. Our findings strongly suggest that 10p15.1 harbours a gene involved in repression of telomerase RNA component in human somatic cells and each putative repressor (on 3p and 10p) may act independently.

Carcinoid Tumor↗

Release of mercury from dental amalgam fillings in pregnant rats and distribution of mercury in maternal and fetal tissues.

Mercury vapor released from a single amalgam restoration in pregnant rats and mercury concentrations in maternal and fetal rat tissues were studied. Dental treatment was given on day 2 of pregnancy. Mercury concentration in air sample drawn from the metabolism chamber with the rat was measured serially for 24 h on days 2, 8 and 15 of pregnancy. An average mercury concentration in the air samples from the rats given amalgam restorations was 678.6+/-167.5 ng/day on day 2. The average mercury concentration in the air samples tended to decline as time elapsed but a marked amount (423.2+/-121.5 ng/day) was observed even on day 15. The amount of mercury in the air samples increased 7--20-fold after chewing. The placement of the single amalgam restoration (3.8--5.5 mg in weight) increased the levels of mercury approximately three to 6 times in the maternal brain, liver, lung, placenta and 20 times in the kidneys. The highest mercury concentration among fetal organs was found in the liver, followed by the kidneys and brain. Mercury concentrations in maternal organs and fetal liver were significantly higher than those of the controls, and concentrations in maternal whole blood, erythrocytes and plasma, and in fetal whole blood were also significantly higher. Mercury concentrations in the fetal brain, liver, kidneys and whole blood were lower than those of the maternal tissues.

Air↗

Loss of heterozygosity of the mannose 6-phosphate/insulin-like growth factor II receptor and p53 genes in human hepatocellular carcinoma.

Information about M6P/IGF2R and p53 genes in hepatocarcinogenesis is limited and controversial. We tested the loss of heterozygosity (LOH) of M6P/IGF2R and p53 genes in cirrhotic and neoplastic foci in surgically resected livers of 30 patients with hepatocellular carcinoma (HCC). The DNAs extracted from microdissected specimens were used for polymerase-chain-reaction (PCR)-based assay. LOH of the M6P/IGF2R gene in the primary HCCs was detected in 10 of 22 informative cases (45%). In five of these 10 cases (50%), LOH was detected in cirrhotic lesions adjacent to the HCCs. The allelic loss patterns of M6P/IGF2R in liver cirrhosis (LC) were identical to those in the corresponding HCC, suggesting that HCC could develop from one of the cells in which M6P/IGF2R had been lost. Furthermore, LOH of the p53 gene in HCC was detected in 10 (43%) of 23 informative cases, and p53 loss in cirrhotic foci adjacent to HCC was shown in one of the 10 cases (10%). The pattern of allelic loss of the p53 gene in the cirrhotic foci was identical with that in the corresponding tumor. The LOH of the M6P/IGF2R and p53 genes occurred independently in HCCs. LOH of the M6P/IGF2R locus was a relatively frequent and possibly early event in hepatocarcinogenesis, and LOH of the M6P/IGF2R gene and LOH of the p53 gene occurred independently.

Journal Article↗

Hyperpolarizing shift by quinine in the steady-state inactivation curve of delayed rectifier-type potassium current in bullfrog sympathetic neurons.

Whole-cell recordings were made from dissociated bullfrog sympathetic neurons to examine the actions of quinine (1-100 microM) on the steady-state activation and inactivation curves of a delayed rectifier-type potassium current (I(K)). Quinine (EC50 approximately 8 microM) caused a hyperpolarizing shift (approximately 31 mV with 30 microM) in the inactivation curve of I(K) without significantly affecting its activation curve. Quinine (20 microM) was without effects on the voltage-dependence of a rapidly-inactivating A-type potassium current (I(A)). It is concluded that quinine can selectively modulate the voltage-dependence of I(K) in amphibian autonomic neurons.

Animals↗

Chronic inborn erythrocytosis leads to cardiac dysfunction and premature death in mice overexpressing erythropoietin.

The most common cause of an increase of the hematocrit is secondary to elevated erythropoietin levels. Erythrocytosis is assumed to cause higher blood viscosity that could put the cardiovascular system at hemodynamic and rheological risks. Secondary erythrocytosis results from tissue hypoxia, and one can hardly define what cardiovascular consequences are caused by chronic erythrocytosis or hypoxia. Herein, a novel transgenic (tg) mouse line is characterized that is erythrocytotic because of chronic overexpression of the human erythropoietin gene. These mice grow up well, reaching a hematocrit of about 0.80 in adulthood. Blood volume of adult tg mice was markedly increased by 75%. Unexpectedly, blood pressure was not elevated and cardiac output was not decreased. Still, the adult tg mice showed features of cardiac dysfunction with increased heart weight. In vivo, high-frequency echocardiography revealed marked ventricular dilatation that was confirmed by histologic examination. Furthermore, by transmission electron microscopy, a prominent intracellular edema of the cardiomyocytes was seen. Exercise performance of the tg mice was dramatically reduced, unmasking the severity of their compromised cardiovascular function. In addition, life expectancy of the tg mice was significantly reduced to 7.4 months. Our findings suggest that severe erythrocytosis per se results in cardiac dysfunction and markedly reduced life span.

Age Factors↗