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Biomedical subjects

Y Takei

Publications and source records attributed to Y Takei.

At least 199 records · Page 11Linked to original sources
PubMed1995

Synapsin I deficiency results in the structural change in the presynaptic terminals in the murine nervous system.

Synapsin I is one of the major synaptic vesicle-associated proteins. Previous experiments implicated its crucial role in synaptogenesis and transmitter release. To better define the role of synapsin I in vivo, we used gene targeting to disrupt the murine synapsin I gene. Mutant mice lacking synapsin I appeared to develop normally and did not have gross anatomical abnormalities. However, when we examined the presynaptic structure of the hippocampal CA3 field in detail, we found that the sizes of mossy fiber giant terminals were significantly smaller, the number of synaptic vesicles became reduced, and the presynaptic structures altered, although the mossy fiber long-term potentiation remained intact. These results suggest significant contribution of synapsin I to the formation and maintenance of the presynaptic structure.

Animals↗
PubMed1995

Glycosylated human recombinant interleukin-1 alpha, neo interleukin-1 alpha, with D-mannose dimer exhibits selective activities in vivo.

To investigate the effect of carbohydrate-introduction on IL-1 activity, especially in vivo, and to develop IL-1 with less deleterious effects, recombinant human IL-1 alpha was coupled with mannose dimer, alpha-D-Man-1-6-D-Man [Man2 alpha(1-6)] by an acyl azide method. Previous studies demonstrated that the glycosylated IL-1 exhibited reduced activities compared with original IL-1 in all the experiments performed in vitro. In this study, we investigated the in vivo activities of Man2 alpha(1-6)-conjugated IL-1 alpha. The glycosylated IL-1 alpha exhibited very low pyrogenic activity and alpha 1-acid glycoprotein induction compared with untreated IL-1 alpha. Untreated IL-1 alpha increased the serum level of IL-6, but the glycosylated IL-1 alpha did not. However, the glycosylated IL-1 alpha possessed the same potency as untreated IL-1 alpha in reduction of serum levels of glucose and triglyceride and in recovery of peripheral white blood cells in 5-fluorouracil-treated mice. Therefore, glycosylation of IL-1 appeared to be useful for the development of neoIL-1 with selective activity in vivo.

Animals↗
PubMed1995

Mechanism for ammonia-induced promotion of gastric carcinogenesis in rats.

Although an association is suggested between gastric cancer and prior infection with Helicobacter pylori (HP), the role of HP in gastric carcinogenesis remains obscure. HP has potent urease activity and produces ammonia, a factor causing HP-related gastroduodenal mucosal lesions. In this study, rats were examined in an effort to determine effects of ammonia on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). After pretreatment with MNNG (83 mg/l) for 24 weeks, a solution of either 0.01% ammonia or plain tap water was administered to the animals as drinking water for an additional 24 weeks. The administration of the 0.01% ammonia solution significantly increased the incidence and number of cancers in the glandular stomach. The numbers of cases in which these cancers penetrated the muscle layer or deeper and of low-grade differentiated adenocarcinomas were significantly higher in rats receiving the ammonia solution. Continuing administration of ammonia accelerated cell proliferation in the gastric mucosa, but had no effect on the serum gastrin level. Therefore, gastric ammonia, which stimulates mucosal cell proliferation, appears to be an important promoter in carcinogenesis in rats and possibly in the HP-related gastric carcinogenesis in humans.

Ammonia↗
PubMed1995

Apoptosis: a new mechanism of endothelial and Kupffer cell killing.

Kupffer cells (KC) become activated in response to lipopolysaccharide (LPS) and produce a variety of mediators. Among them, TNF alpha is known to injure the liver. Here we report that TNF alpha mediates apoptosis in KC and sinusoidal endothelial cells. After stimulation for 24 h with LPS (0-10 micrograms/mL), apoptosis in KC detected by TUNEL TdT-mediated dUTP-biotin nick end labelling (TUNEL) increased in a concentration-dependent manner (0 micrograms/mL, 12 +/- 4%; 0.1 microgram/mL, 36 +/- 11%; 1.0 micrograms/mL, 65 +/- 9%; 10 micrograms/mL, 78 +/- 15%). In contrast, co-incubation of endothelial cells with LPS-stimulated KC resulted in a marked increase in TUNEL-positive endothelial cells. TNF alpha antibody blocked apoptosis in both KC and endothelial cells. Apoptosis was observed in cells adjacent to or in contact with KC. Reducing transmembrane TNF alpha expressed on KC also led to a decrease in endothelial cell apoptosis, suggesting that transmembrane TNF alpha is implicated in the cell-to-cell contact mechanism of induction of apoptosis. Thus, TNF alpha mediates apoptosis in KC and endothelial cells.

Animals↗
PubMed1995

[Primary lung cancer in young patients].

We studied the clinical characteristics and prognosis of patients, 40 years old or younger, in whom primary lung cancer was diagnosed and treated at National Nishigunma Hospital between 1982 and 1993, and compared them with those of 978 patients more than 40 years old. Younger patients numbered 30 (3.0%). Females accounted for 16 of the 30 cases (53.3%), a proportion higher than the female: male ratio for the older patients (27.8%). There were more smokers among the older patients (72.8%) than among the younger patients (53.3%) (p < 0.01). Adenocarcinoma was significantly more common (19/30, 63.3% vs 43.8%, p < 0.05) and squamous cell carcinoma was less common (3.30, 10.0% vs 34.3%, p < 0.05) in the younger patients than in the older patients. Median survival time in younger patients was 30.0 months, and in older patients it was 14.6 months, but we found no significant difference in survival between younger and older patients. In the younger group, all the cases of stage I or II disease were discovered during mass screening.

Adenocarcinoma↗
PubMed1995

Gastric mucosal cell proliferation and TGF alpha in the healing of peptic ulcers in human subjects.

We investigated the role of gastric mucosal proliferation and mucosal transforming growth factor-alpha (TGF alpha) in the healing of peptic ulcers in human subjects. During endoscopic observation, mucosal biopsy specimens were taken from the ulcer margin for flow cytometric analysis of the mucosal cell cycle and ELISA for mucosal TGF alpha content. Immunohistochemistry confirmed that biopsy specimens contained proliferating gastric epithelial cells, TGF alpha, and the TGF alpha receptor. When the stage of ulcer healing was categorized according to Sakita and Miwa, mucosal cell proliferation was less at active stages and gradually increased during the healing process. The mucosal TGF alpha level at the ulcer margin was not detectable at the A1 stage but increased to within the normal range during ulcer healing. After re-establishment of the epithelial layer at the site of the ulcer, cell proliferation returned to normal and TGF alpha remained within the normal range. Immunohistochemistry showed coexistence of TGF alpha and its receptor within PCNA-positive proliferating cells. These results suggest that TGF alpha and its receptor play an important role in gastric epithelial cell replication. The increase in TGF alpha at the ulcer margin might indicate a role in stimulation of gastric cell replication during ulcer healing.

Adult↗
PubMed1994

Cloning and expression of eel natriuretic-peptide receptor B and comparison with its mammalian counterparts.

A comparative study of the natriuretic-peptide receptor NPR-B was performed by cloning and expressing, in COS-1 cells, the NPR-B receptor subtype from the eel gill which exhibited a strong C-type-natriuretic-peptide (CNP)-induced guanylate cyclase activity. Like other mammalian NPR-B receptors, the eel NPR-B receptor consisted of a ligand-binding extracellular domain, a hydrophobic transmembrane domain, a kinase-like domain and a guanylate cyclase domain. Sequence comparison among the eel and mammalian receptors revealed a relatively low similarity (approximately 44%) in the extracellular domain compared to a very high similarity (approximately 84%) in the cytoplasmic regulatory and catalytic domains. This low similarity allowed identification of the amino acid residues or candidate regions important for the ligand-binding activity. RNase protection analysis of the eel NPR-B mRNA demonstrated that the message was predominantly expressed in the liver and atrium as well as in the gill with moderate-to-small amounts in the brain, ventricle, esophageal sphincter, stomach, posterior intestine and kidney. The high NPR-B mRNA levels in the liver, atrium and gill were found to decrease markedly when eels were transferred from fresh water to seawater and kept there for 2 weeks. Since similar changes are known to occur in the ligand CNP levels when eels are facing osmotic challenges, the CNP/NPR-B system appears to play an important role in their successful adaptation to salinity changes.

Amino Acid Sequence↗
PubMed1994

Altered microtubule organization in small-calibre axons of mice lacking tau protein.

The tau gene encodes a protein (Tau) that is a major neuronal microtubule-associated protein localized mostly in axons. It has microtubule-binding and tubulin-polymerizing activity in vitro and is thought to make short crossbridges between axonal microtubules. Further, tau-transfected non-neuronal cells extend long axon-like processes in which microtubule bundles resembling those in axons are formed. In contrast, tau antisense oligonucleotides selectively suppress axonal elongation in cultured neurons. Thus tau is thought to be essential for neuronal cell morphogenesis, especially axonal elongation and maintenance. To test this hypothesis, we used gene targeting to produce mice lacking the tau gene. We show that the nervous system of tau-deficient mice appears to be normal immunohistologically. Furthermore, axonal elongation is not affected in cultured neurons. But in some small-calibre axons, microtubule stability is decreased and microtubule organization is significantly changed. We observed an increase in microtubule-associated protein 1A which may compensate for the functions of tau in large-calibre axons. Our results argue against the suggested role of tau in axonal elongation but confirm that it is crucial in the stabilization and organization of axonal microtubules in a certain type of axon.

Animals↗
PubMed1994

Pertussis toxin-catalyzed ADP-ribosylation of GTP-binding proteins with digoxigenin-conjugated NAD. Identification of the proteins in plasma membranes and nuclei.

ADP-ribose moiety containing digoxigenin was transferred by pertussis toxin (IAP) to the alpha subunit of Gi (Gi alpha) from digoxigenin-conjugated NAD (DIG-NAD) in a beta gamma subunit-dependent manner. ADP-ribosylation of Gi alpha with DIG-NAD plus IAP was inhibited by native NAD. These results indicate that non-radiolabeled DIG-NAD also serves as the substrate for IAP-catalyzed ADP-ribosylation of G proteins. Using DIG-NAD and fluorescein isothiocyanate-labeled anti-digoxigenin antibody, IAP-sensitive G protein(s) was found to be exist in nuclei as well as plasma membranes of rat liver and HeLa cells. Thus, DIG-NAD is useful to identify pertussis toxin-substrate G proteins.

Adenosine Diphosphate Ribose↗
PubMed1994

Endothelin-1 is involved in the pathogenesis of ischemia/reperfusion liver injury by hepatic microcirculatory disturbances.

Hepatic microcirculatory perturbation is observed after ischemia/reperfusion. Endothelin-1, a potent vasoconstrictive peptide, is known to modulate local circulation. This study was designed to examine whether endothelin-1 participates in the mechanism of microcirculatory disturbance and damage of the liver after ischemia/reperfusion. Ischemia in the median and left lateral lobes of the liver was induced for 60 min; it was followed by reperfusion for 24 hr. In some rats, endothelin-1 antiserum or control serum without endothelin-1-blocking activity was administered intravenously just before reperfusion. Rats were divided into three groups: an ischemia/reperfusion group that was injected with control serum, an endothelin-1 antiserum-treated group and a sham-operated group. Endothelin-1 concentrations in blood collected from the suprahepatic vena cava were measured before and after ischemia/reperfusion by use of a sandwich enzyme immunoassay. Index of blood volume in regional hepatic tissue and index of blood oxygenation in regional hepatic tissue were assessed with an organ reflectance spectrophotometry system before and at 5 min and 1, 2, and 24 hr after reperfusion. The endothelin-1 concentration in the ischemia/reperfusion group started to rise immediately at onset of reperfusion from basal values around 1 pg/ml and reached a value of 5 to 6 pg/ml 5 min after reperfusion; it was maintained at significantly high levels during the reperfusion period compared with the sham-operated group. Hepatic microcirculatory disturbance indicated by lowered index of blood volume in regional hepatic tissue and index of blood oxygenation in regional hepatic tissue levels was observed in the early phase of reperfusion in the ischemia/reperfusion group.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1994

Endogenous nitric oxide attenuates ethanol-induced perturbation of hepatic circulation in the isolated perfused rat liver.

The purpose of this study was to clarify the role of endogenous nitric oxide in ethanol-induced perturbation of microcirculation and hepatic injury in perfused rat liver. Infusion of ethanol into the portal vein at 25 and 100 mmol/L increased portal pressure, which is an indicator of hepatic vasoconstriction, in a concentration-dependent fashion. Portal pressure started to rise immediately after ethanol load, then decreased gradually and remained at higher than basal levels throughout the period of ethanol infusion. Release of lactate dehydrogenase into the effluent perfusate began to increase after 30 min of ethanol infusion and continued to increase during the 60-min period of ethanol infusion. The lactate dehydrogenase level in the effluent perfusate at 60 min was dependent on the ethanol concentration (0 mmol/L, 8 +/- 3 IU/L; 25 mmol/L, 16 +/- 2 IU/L; 100 mmol/L, 52 +/- 6 IU/L). Simultaneous infusion of NG-monomethyl-L-arginine, a nitric oxide synthesis inhibitor, enhanced significantly the ethanol-induced increase in portal pressure by 100% to 400% and increased lactate dehydrogenase release by 40% to 80%. The effect of NG-monomethyl-L-arginine on the ethanol-induced increase in portal pressure was completely reversed by the co-infusion of an excess dose of L-arginine. Change in portal pressure averaged over 60 min of ethanol infusion correlated with levels of lactate dehydrogenase release 60 min after the initiation of ethanol infusion (r = 0.77, p < 0.01). In conclusion, inhibition of the action of endogenous nitric oxide was associated with an increase in hepatic vasoconstriction and hepatocellular damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Distribution and molecular forms of C-type natriuretic peptide in plasma and tissue of a dogfish, Triakis scyllia.

A radioimmunoassay (RIA) to measure C-type natriuretic peptide (CNP) of a dogfish, Triakis scyllia, was established, and plasma and tissue levels of CNP were measured. Molecular forms of CNP in plasma and tissues were also examined using a combination of the RIA and cation-exchange high-performance liquid chromatography (HPLC). The antibody used in the assay cross-reacted with all forms of Triakis CNP, as well as eel CNP, against which the antibody was raised. The antibody exhibited no cross-reaction with any atrial, brain (B-type), and ventricular natriuretic peptides examined and showed a weak cross-reaction with porcine CNP. The detection limit of this assay was 0.8 fmol/tube of Triakis CNP-22 which was used as standard. The CNP level in the Triakis plasma was 1.97 +/- 0.38 pmol/ml (n = 5) which far exceeded the physiological levels of any natriuretic peptides in other species. Among various tissues examined, the highest concentration of CNP was measured in the atrium, followed by the ventricle, brain, and pituitary. Low levels were detected in the kidney, liver, and digestive tracts. HPLC analyses revealed that the major form of CNP in the brain was CNP-22, while it was proCNP (CNP-115) in the heart. In contrast to other species from teleosts to mammals thus far examined, the majority of CNP in dogfish plasma was prohormone instead of processed, mature forms.

Animals↗
PubMed1994

Rainbow trout ventricular natriuretic peptide: isolation, sequencing, and determination of biological activity.

Ventricular natriuretic peptide (VNP) is a new type of cardiac natriuretic peptide initially isolated from the eel ventricle. VNP has been isolated from cardiac ventricles of the rainbow trout, Oncorhynchus mykiss, and found to consist of 35 amino acid residues carrying a C-terminal tail sequence with 14 amino acid residues. Thus, the long C-terminal sequence characteristic of VNP was also conserved in the trout VNP. A VNP with 4 amino acid residues truncated from the C-terminus was also isolated from trout ventricles and sequenced. Sequence identity of trout VNP to eel VNP was 77%; while it was 56% to eel A-type natriuretic peptide (ANP). Trout VNP caused characteristic biphasic vasopressor/depressor effects in the trout similar to those produced by rat and eel ANP. Trout VNP and human ANP were almost equipotent in their vasopressor and depressor activity in trout. Unlike eel VNP, therefore, homologous VNP did not exhibit greater activity in the trout. In the rat, however, trout VNP was more potent than eel peptide and was almost equipotent to human ANP for both vasodepressor and natriuretic effects. The high potency of trout VNP appears to be due in part to its longer-lasting effect compared to human ANP.

Amino Acid Sequence↗
PubMed1994

Impaired gastric mucosal energy metabolism in congestive gastropathy in cirrhotic patients.

To clarify the characteristics of congestive gastropathy, we investigated gastric mucosal hemodynamics and energy metabolism in cirrhotic patients, using a reflectance spectrophotometry system and high performance liquid chromatography. The index of the gastric mucosal blood volume of cirrhotic patients with esophageal varices was significantly higher, and the index of gastric mucosal blood oxygenation significantly lower, than those in controls, thus indicating congestion and hypoxia in the gastric mucosa. Energy charge levels in the gastric mucosa of cirrhotic patients with esophageal varices were also significantly decreased. The energy charge level showed a strong linear correlation with the index of mucosal blood oxygenation in the antral (r = 0.996, P < 0.01) and body (r = 0.994, P < 0.01) mucosa of the stomach. These findings suggest that congestive gastropathy in a portal hypertensive state causes hypoxia in the gastric mucosa, leading to a mucosal energy deficit that may increase mucosal susceptibility to aggressive factors.

Chromatography, High Pressure Liquid↗
PubMed1994

Role of endothelin 1 in hemorrhagic shock-induced gastric mucosal injury in rats.

BACKGROUND/AIMS: Gastric microcirculatory disturbances are involved in the pathogenesis of stress ulcers; however, vasomodulators regulating this process are not fully understood. This study was conducted to investigate the role of endothelin 1 (ET-1) in hemorrhagic shock-induced gastric mucosal damage in rats. METHODS: ET-1 contents in plasma and gastric mucosa were measured and gastric mucosal damage was evaluated during a control period, 60 minutes of ischemia, 15 minutes of reperfusion, and 30 minutes of postreperfusion. Next, effects of BQ-123, an endothelinA receptor antagonist, on the gastric mucosal damage and hemodynamics were studied. RESULTS: Both plasma and mucosal ET-1 significantly increased after ischemia and reperfusion compared with the control values, but only mucosal ET-1 continued to increase after reperfusion, leading to the development of gastric mucosal damage. BQ-123, administered just before reperfusion, reduced mucosal damage in the postreperfusion period dose-dependently and improved mean gastric mucosal blood flow and mucosal hemoglobin oxygen saturation during the 30-minute postreperfusion period. CONCLUSIONS: These results suggest that endogenous ET-1 plays an important role in the pathogenesis of hemorrhage shock-induced gastric mucosal damage through impairment of mucosal microcirculation. Further, endothelinA antagonists may have therapeutic benefits for shock-induced gastric mucosal damage.

Animals↗
PubMed1994

Vasoactive effect of endothelin-1 on rat liver in vivo.

The purpose of this study was to evaluate the role of endothelin-1 in modulating hepatic microcirculation and liver damage. Rats were infused with endothelin-1 at doses ranging from 30 to 1,000 pmol/kg over 1 min through an indwelling cannula placed in the portal vein. In control rats, saline solution was infused at the same rate. Alterations in hepatic microcirculation were measured with an in vivo microscopy system. Serum lactate dehydrogenase activity, an indicator of hepatic damage, was measured 1 hr after endothelin-1 infusion. Immediately after infusion of endothelin-1, we noted a rapid increase in portal pressure, which remained increased for up to 30 min after endothelin-1 infusion. In contrast, systemic blood pressure remained unchanged, even at 1,000 pmol/kg of endothelin-1. Sinusoidal width was reduced and sinusoidal erythrocyte velocity was diminished in a dose-dependent manner. Oxygen saturation of blood in sinusoids was decreased in a dose-dependent manner, reaching values around 40% of control with 1,000 pmol/kg endothelin-1. The degree of decrease in oxygen saturation of blood in sinusoids had an excellent correlation with the calculated blood flow in the liver tissue. Serum lactate dehydrogenase levels were three to four times control values when endothelin-1 was administered at 1,000 pmol/kg. Thus endothelin-1 decreased hepatic tissue oxygenation associated with sinusoidal vasoconstriction. At high concentrations of endothelin-1, this decrease results in hepatocellular damage.

Animals↗