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Biomedical subjects

Y Takeuchi

Publications and source records attributed to Y Takeuchi.

At least 271 records · Page 15Linked to original sources
PubMed1999

The long-lasting effect of TU-199, a novel H+, K(+)-ATPase inhibitor, on gastric acid secretion in dogs.

We have used Heidenhain-pouch dogs to investigate the effects of (+/-)-5-methoxy-2-{[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulph inyl}-1H-imidazo[4,5-b]pyridine (TU-199), an imidazopyridine derivative, on gastric acid secretion stimulated by histamine, carbachol and tetragastrin. We have also investigated the duration of the antisecretory effect of TU-199 using a measurement of intragastric pH for 24 h in gastric fistula dogs whose gastric acid secretion was stimulated by histamine. Single oral administration of TU-199 (0.1, 0.2 and 0.4mgkg(-1)) dose-dependently suppressed gastric acid secretion stimulated by histamine infusion. Oral treatment with TU-199 (0.2, 0.4 and 0.8 mg kg(-1)) also dose-dependently inhibited acid secretion induced by carbachol and tetragastrin. The inhibitory effect of TU-199 on stimulated gastric acid secretion was more potent than that of omeprazole, a well-known H+,K(+)-ATPase inhibitor in dogs. Repeated oral treatment with TU-199 at a dose of 0.2 mg kg(-1) once a day for seven days markedly suppressed histamine-stimulated gastric acid secretion in dogs. This inhibitory effect of TU-199 reached a maximum level after three or four doses and was more pronounced than that of omeprazole or lansoprazole. In gastric fistula dogs, the duration of intragastric pH-elevation by administration of TU-199 (0.3 mg kg(-1)) was much longer than that of omeprazole (0.6mgkg(-1)) or lansoprazole (0.9mgkg(-1)). The IC50 values (doses resulting in 50% inhibition) of TU-199, omeprazole and lansoprazole with regard to H+,K(+)-ATPase activity in dog gastric mucosal microsomes were 8.6, 8.8 and 9.9 microM, respectively. These results indicate that TU-199 inhibits gastric acid secretion via suppression of a H+,K(+)-ATPase activity. Our findings also suggest that TU-199 might have potent and long-lasting effects on gastric acid secretion.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Enhancement of propylene glycol distribution in the skin by high purity cis-unsaturated fatty acids with different alkyl chain lengths having different double bond position.

Enhancement of skin distribution of propylene glycol (PG) in the skin by high purity cis-unsaturated fatty acids with different alkyl chain lengths was studied in the rat using Fourier transform/attenuated total reflection (FT-IR/ATR) analysis. Two fatty acids with the double bond at the delta9 position, palmitoleic acid (omega7, delta9) and oleic acid (omega9, delta9), enhanced PG flux into the dermis and increased the dermal steady state level of PG. In contrast, myristoleic acid (omega5, delta9) was extremely weak in its action. A positional effect of the omega chain was observed. The rate of skin structural alteration increased in proportion to omega chain length. The application of three fatty acids with the double bond at the omega9 position, oleic acid (omega9, delta9), gondoic acid (omega9, delta11), erucic acid (omega9, delta13) enhanced PG distribution in the skin. While, nervonic acid (omega9, delta15) did not increase PG distribution in the skin. The relationship of the delta/omega ratio to parameters characterizing the action of enhancers (PG(peak area max), T(max alteration), and the slope) suggest that skin distribution increases as the position of the double bond is shifted toward the hydrophilic end. It is therefore likely that the ratio of the delta/omega chain length of the cis-unsaturated fatty acid determines the efficacy of these compounds as skin penetration enhancers. An adequate molecular volume may be required for cis-unsaturated fatty acids to act as enhancers.

Animals↗
PubMed1999

Correlation of a defect of portal perfusion in the dorsal part of segment IV of the liver on CT arterial portography with inflow of the aberrant pancreaticoduodenal vein.

The correlation between an aberrant pancreaticoduodenal vein and a portal perfusion defect in the dorsal part of segment IV as demonstrated on CT arterial portography (CTAP) was investigated. 14 patients with non-tumorous defects of portal perfusion in the dorsal part of segment IV of the liver parenchyma, shown on CTAP underwent CT during pancreaticoduodenal arteriography. The defect on CTAP was shown as an enhanced area resulting from non-portal venous inflow in eight (57%) of 14 patients on CT during pancreaticoduodenal arteriography. In conclusion, the non-portal venous supply via an aberrant pancreaticoduodenal vein occasionally causes a defect of portal perfusion in the dorsal part of segment IV on CT arterial portography.

Aged↗
PubMed1999

Intrahepatic portosystemic venous shunt associated with a large abdominal tumour.

Intrahepatic portosystemic venous shunt (IPSVS) is relatively uncommon, and is usually associated with chronic hepatitis or cirrhosis. We present a case of IPSVS that was considered to be caused by increased blood flow from a large abdominal tumour. The characteristic intrahepatic haemodynamics were demonstrated by CT angiography.

Hepatic Veins↗
PubMed1999

Effects of TU-199, a novel H+, K(+)-ATPase inhibitor, on gastric acid secretion and gastroduodenal ulcers in rats.

We studied the effects of TU-199, a novel H+, K(+)-ATPase inhibitor, on gastric acid secretion and gastroduodenal lesions in rats in comparison with those of omeprazole. TU-199 inhibited hog gastric H+, K(+)-ATPase activity and its potency was almost equal to that of omeprazole (IC50 = 6.2 and 4.2 microM, respectively). In vivo, TU-199 inhibited basal gastric acid secretion in pylorus-ligated rats in a dose-dependent manner (ED50 = 4.2 mg/kg p.o.). In gastric fistula rats. TU-199 (2.5 and 5 mg/kg i.d.) also inhibited gastric acid secretion stimulated by histamine, carbachol or tetragastrin. Furthermore, TU-199 prevented the formation of water-immersion restraint stress-, pylorus ligation- and indomethacin-induced gastric lesions, and mepirizole-induced duodenal ulcer in rats. These antisecretory and antiulcer effects of TU-199 were 2-4 times more potent than those of omeprazole. The results demonstrate that TU-199 potently inhibits the acid secretion and formation of ulcers in various experimental rat models via an inhibition of H+, K(+)-ATPase. These findings suggest that TU-199 may have a beneficial effect against peptic ulcer disease in humans.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

The primary calcification in bones follows removal of decorin and fusion of collagen fibrils.

To elucidate the mechanisms of primary calcification in bone, ultrastructural changes in collagen fibrils, as well as cytochemical alteration of proteoglycan, especially decorin, were investigated morphologically in 19-day postcoitum embryonic rat calvariae. Below the osteoblast layer, calcification of the osteoid area increased in direct proportion to its distance from the osteoblasts. In the uncalcified osteoid area, collagen fibrils near matrix vesicles possessed sharp contours and were a uniform 50 nm in diameter. Immunoelectron microscopy revealed decorin to be abundantly localized in the vicinity of the collagen fibrils. In the osteoid area undergoing the process of calcification, collagen fibrils tended to fuse side by side. Where calcification was progressed, this fusion was even more so. Some very large fibrils exhibited complicated contours, 400 nm or more in diameter. Although the calcification at this stage affected areas both inside and outside of the collagen fibrils, the interior areas manifested a lower density of calcification. The immunolocalization of decorin was also much decreased around these fibrils. Thus, primary calcification in bone matrix follows the removal of decorin and fusion of collagen fibrils. This phenomenon may aid in the process of calcification and bone formation, because (1) inhibitors of calcification, such as decorin, are removed, (2) the fusion of collagen fibrils provides the room necessary for rapid growth of mineral crystals, and (3) the soft elastic bone matrix containing abundant fused collagen fibrils less subjective to calcification is safe for both maternal and embryonic bodies and is convenient for subsequent bone remodeling.

Animals↗
PubMed1999

Electrophysiological correlates of pulsatile and surge gonadotrophin secretion.

The hypothalamic gonadotrophin-releasing hormone (GnRH) pulse generator governs intermittent discharges of GnRH into the pituitary portal circulation and, consequently, modulates the pulsatile pattern of gonadotrophin secretion. Electrophysiological correlates of pulsatile gonadotrophin secretion have been demonstrated in the mediobasal hypothalamus of monkeys, rats and goats by recording multiple unit activity. A temporal coincidence between characteristic increases in multiple unit activity and gonadotrophin pulses in the circulation is seen under a variety of physiological and experimental conditions in all three species examined, providing evidence that hypothalamic multiple unit activity originates in the GnRH pulse generator. During a preovulatory gonadotrophin surge induced by oestrogen in ovariectomized animals or occurring spontaneously in intact animals, GnRH pulse generator activity is decelerated, suggesting that it is not involved in generating the gonadotrophin surge. The gonadotrophin surge may be generated by an oestrogen-responsive neuronal complex intrinsically different from the GnRH pulse generator, the electrical operation of which remains unknown.

Animals↗
PubMed1999

Klinefelter's syndrome accompanied by mixed connective tissue disease and diabetes mellitus.

We report a rare case of Klinefelter's syndrome (KS) with mixed connective tissue disease (MCTD), diabetes mellitus (DM) and several endocrine disorders. A 57-year-old man presented with polyarthritis and tapering fingers with Raynaud's phenomenon on admission. In addition to a karyotype of 47, XXY, a marked restrictive change in respiratory functional test, a myogenic pattern in electromyogram, the positive tests for anti-RNP antibody indicated that this was a case of KS complicated with MCTD. The patients also presented DM with insulin resistance, hyperprolactinemia, slight primary hypothyroidism and hypoadrenocorticism. The mechanism for these coincidences remains to be elucidated.

Arthritis↗
PubMed1999

The cause of nontumorous defects of portal perfusion in the hepatic hilum revealed by CT during arterial portography.

OBJECTIVE: We investigated the cause of nontumorous defects of portal perfusion in the hepatic hilum revealed by CT during arterial portography (CTAP). MATERIALS AND METHODS: One hundred sixty patients who simultaneously underwent CTAP and CT during hepatic arteriography of the common hepatic artery formed the basis of our study. The frequency, site, and shape of nontumorous defects of portal perfusion in the hepatic hilum on CTAP and the findings on CT during hepatic arteriography were determined. In 13 patients in whom nontumorous portal perfusion defects were observed on CTAP, CT was performed during selective angiography via the gastric artery, pancreaticoduodenal artery, or both. RESULTS: Nontumorous defects of portal perfusion were detected in 49 regions in 33 of the 160 patients (dorsum of segment IV, n = 30; dorsum of the lateral segment, n = 11; segment I, n = 8). Of the 33 patients, 16 had two defects each. Of the 49 nontumorous defects of portal perfusion, 38 showed enhancement on CT during hepatic arteriography. In the 13 patients who underwent CT during selective arteriography, enhancement due to nonportal venous inflow was seen in 16 of the 19 areas of decreased nontumorous portal perfusion (dorsum of segment IV, nine of 11; dorsum of the lateral segment, four of five; segment I, three of three). CONCLUSION: The main cause of nontumorous defects of portal perfusion in the hepatic hilum revealed by CTAP is decreased portal inflow due to nonportal supply via the parabiliary venous system. Thus, such lesions were also enhanced at a high frequency on CT during hepatic arteriography.

Aged↗
PubMed1999

Simple synthesis of alpha-cyano-alpha-fluoro-p-tolylacetic acid (CFTA), a new efficient chiral derivatizing agent.

The new chiral derivatizing agent, alpha-cyano-alpha-fluoro-p-tolylacetic acid (CFTA) (2) was prepared in optically pure form by Candida rugosa lipase (CRL)-mediated kinetic resolution of racemic CFTA ethyl ester (CFTA Et ester) (1). The ester was obtained by fluorination of ethyl alpha-cyano-p-tolylacetate with FClO3. The CFTA method has proven to be significantly superior for enantiomeric excess (e.e.) determinations when compared to the MTPA method, particularly in those compounds that have a remotely disposed chiral center.

Acetates↗
PubMed1999

[Optimum anticoagulation control after bileaflet mechanical valve replacement: a prospective multi-institutional study].

This study was undertaken to assess optimum anticoagulation control after bileaflet mechanical valve replacement by using the international normalized ratio of prothrombin time (PT-INR). From January to December 1995, 261 patients (pts) underwent mechanical valve replacement in the aortic (n = 95), mitral (n = 126), aortomitral (n = 39) or isolated tricuspid (n = 1) valve position in 8 medical centers in Tokyo, Japan. The St. Jude Medical valves were implanted in 184 pts and the Carbomedics valves in 77. There were 17 valve-related events as follows: 11 thromboembolic events (3.62%/pt-yr) including 10 transient ischemic attacks. 5 non-fatal bleeding events (1.65%/pt-yr), 2 reoperations (0.66%/pt-yr). At 18 postoperative months, free rates from all deaths (actuarial survival) thromboembolism, reoperation and all valve-related events were 95.3%, 95.7%, 98.7% and 88.9%, respectively. Under anticoagulant therapy, thrombin-antithrombin III complex and D-dimmer remained in high levels at 1 month after operation, and both values decreased to the control level at 6 months. In patients with thromboembolic events, PT-INR tended to be less than 2.0. The patients with bleeding events showed some increase of PT-INP or received anti-platelet agents. The 5 to 95 percentile of PT-INR at 6 months was 1.2 to 3.0 in the patients without valve-related events. These results suggested that optimum range of PT-INR might be between 1.2 and 3.0 after bileaflet mechanical valve replacement in patients without high risk of thromboembolism and between 2.0 and 3.0 in patients with the high risk.

Adolescent↗
PubMed1999

Cardiac afferents to the nucleus of the tractus solitarius: A WGA-HRP study in the rat.

Central distribution of the sensory fibers of the heart was investigated in the rat by the use of transganglionic transport of horseradish peroxidase (HRP). After the left intercostal thoracotomy was done under deep anesthesia and artificial respiration, wheat germ agglutinin-conjugated HRP (WGA-HRP) was injected into the left and right ventricular walls and the apex of the heart. HRP-labeled fibers were observed to be distributed to the dorsomedial portion of the medulla oblongata through the vagal nerve. The labeled fibers were present in various subnuclei of the nucleus of the tractus solitarius (NTS) bilaterally at the level of +0.36 to -1.74 mm to the obex. However, the most conspicuous feature in the present study was that the labeled fibers were exclusively confined to the medial, ventrolateral and commissural NTS with some distribution to the dorsolateral NTS. Although the labeling in the medial and ventrolateral NTS was observed to extend rostrocaudally, it was of interest that the labeling in the medial NTS was divided into the ventral and dorsal parts at the level around the obex. Accumulation of the labeled fibers in the commissural NTS was found at the level caudal to the obex and these fibers were traced to the caudal portion of its subnucleus with a gradual decrease in number. This pattern of distribution of cardiac afferents in the NTS was considered to be peculiar to the rat, because it was quite different from that reported previously in the cat.

Afferent Pathways↗
PubMed1999

A newly designed underwater antenna and its application to underwater radio-telemetry for measuring electroencephalographic activity from the rainbow trout freely swimming in natural environments.

A novel underwater antenna (which we named an 'aquaerial') for telemetering the biological signals from freely swimming fish in freshwater natural environments is presented. It is designed for receiving a 90-100 MHz carrier wave and consists of plural unit receiving antennas (UAs). The plural UAs are placed underwater to cover the area where the target fish carrying the transmitter is swimming. The UAs are equally spaced and have a directional coupling amplifier to supply the signals received to the coaxial cable. The optimal length of the UA was found to be 16.5 cm (a half wavelength in water) and optimal spacing was 2 m (one wavelength along coaxial cable) when 95 MHz was used as the carrier frequency. Using this 'aquaerial', long-term monitoring of EEG signals from the olfactory bulb of the rainbow trout (Oncorhynchus mykiss) swimming freely in natural environments was achieved.

Animals↗
PubMed1998

Endogenous retroviruses: a potential problem for xenotransplantation?

To overcome the shortage of suitable human donors for transplantation attention has recently turned to the possibility of using genetically modified pigs as a source of cells and organs. It has been suggested that such procedures might facilitate the introduction of novel retroviruses, normally resident in the pig germ line, into the human population (Stoye and Coffin, Nature Medicine 1: 1100, 1995). The consequences of such a transfer remain unclear; however, the demonstration that certain porcine cell lines express infectious retroviruses which can infect human cells (Patience et al., Nature Medicine 3: 282-286, 1997) emphasizes that there are grounds for practical concern. We have now cloned the envelope genes of the expressed viruses and are using these clones in studies of the interaction of the porcine viruses with their cellular receptors. We have also initiated studies of the inheritance and expression of human-tropic endogenous proviruses present in different pig populations. These studies reveal that at least two classes of human-tropic endogenous porcine retrovirus are widely distributed in pigs (Le Tissier et al., Nature 389: 681-681, 1997). The implications of our results for assessing the potential risk of retroviral transfer during xenotransplantation are discussed.

Animals↗
PubMed1998

The choleretic effects of N-acetylglucosaminides, major urinary metabolites of ursodeoxycholic acid, in bile fistula rats.

We investigated the effects of three bile acids conjugated with N-acetylglucosamine, ursodeoxycholate N-acetylglucosaminide, tauroursodeoxycholate N-acetylglucosaminide and glycoursodeoxycholate N-acetylglucosaminide, on bile flow and biliary excretion of various markers in comparison with ursodeoxycholic acid, tauroursodeoxycholic acid and glycoursodeoxycholic acid in bile fistula rats. These bile acids were infused intravenously at a constant rate of 0.3 or 0.6 micromol/min/100 g b.w. for 2 h. All bile acids examined increased bile flow in a dose-dependent manner. In particular, ursodeoxycholate N-acetylglucosaminide has a longer-lasting effect after its infusion on bile flow than the other bile acids. Furthermore, these bile acids markedly increased biliary total bile acid excretion. At a higher dose level, the coefficient of determination (r2) between the biliary total bile acid excretion and bile flow for ursodeoxycholate N-acetylglucosaminide (r2 = 0.39) was lower than that for the other bile acids (r2 = 0.75-0.92). The ursodeoxycholate N-acetylglucosaminide, as well as tauroursodeoxycholic acid, glycoursodeoxycholic acid, tauroursodeoxycholate N-acetylglucosaminide and glycoursodeoxycholate N-acetylglucosaminide, was mostly excreted in an unchanged form in bile, whereas ursodeoxycholic acid was excreted as a conjugate with taurine. The three N-acetylglucosaminides as well as ursodeoxycholic acid, tauroursodeoxycholic acid and glycoursodeoxycholic acid significantly increased the biliary excretion of cholesterol, phospholipid, bilirubin and total Ca2+. In contrast, the N-acetylglucosaminides significantly decreased in biliary bicarbonate concentration, whereas ursodeoxycholic acid significantly increased biliary bicarbonate concentration. However, tauroursodeoxycholic acid and glycoursodeoxycholic acid did not significantly change the biliary bicarbonate concentration. The results indicate that N-acetylglucosaminides have a choleretic effect in bile fistula rats. Our present study also demonstrates that N-acetylglucosaminides, but not ursodeoxycholic acid, tauroursodeoxycholic acid or glycoursodeoxycholic acid, can significantly reduce the biliary bicarbonate concentration. Furthermore, our findings suggest that ursodeoxycholate N-acetylglucosaminide may partly exert a choleretic effect via mechanisms different from those of the other bile acids.

Animals↗
PubMed1998

Evaluation of pulmonary afferent fibers in the nucleus tractus solitarius: a horseradish peroxidase and c-fos like immunohistochemical study in the rat.

Wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was injected into the rat lung parenchyma, just beneath the lateral surface of the left upper lobe, in order to demonstrate the pulmonary afferents. This injection resulted in heavy accumulation of labeled fibers in the medial nucleus tractus solitarius (NTS). The labeling in the medial NTS was divided into the ventral and dorsal parts at the level around the obex. Some labeling was found in the commissural and ventrolateral NTS. Further confirmation of the central distribution of these pulmonary afferent fibers was made by the expression of fos-like immunoreactivity (FOS-LI) induced by injection of formalin into the lung. It is concluded that afferents of lung parenchyma terminating predominantly in the medial NTS might come from alveoli and terminal bronchioles, because WGA-HRP and formalin injected into the lung are considered to be confined to the terminal areas of the respiratory tract.

Animals↗