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Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 793 records · Page 44Linked to original sources
PubMed1994

A new CCK-A antagonist, KSG-504, administered intraduodenally, inhibits pancreatic secretion in rats.

We studied the effect in anesthetized rats of a new cholecystokinin (CCK) receptor antagonist developed in Japan, KSG-504, administered intraduodenally, on pancreatic exocrine secretion stimulated by exogenous CCK and intraduodenal casein. Intraduodenal administration of KSG-504 in graded doses of 2.5-50 mg/kg/h produced dose-dependent inhibition of pancreatic juice volume and amylase output stimulated by intravenous infusion of CCK-8 in a dose of 0.06 micrograms/kg/h. The ID50 (half-maximal inhibition dose) of KSG-504 for CCK-8-stimulated amylase secretion was 3.4 mg/kg/h. Moreover, intraduodenal KSG-504 (5 and 25 mg/kg/h) dose dependently suppressed pancreatic juice volume, and amylase output increased with intraduodenal infusion of casein (400 mg/h). It is concluded that KSG-504 administered intraduodenally has a significant, potent inhibitory action on the exocrine pancreas stimulated by exogenous CCK and intraduodenal casein.

Animals↗
PubMed1994

CA19-9 as a screening and diagnostic tool in symptomatic patients: the Japanese experience.

Although the prognosis for pancreatic cancer is generally poor, the Japanese Pancreatic Cancer Register reported in 1992 that the survival rate for resected pancreatic cancer was much higher than that for more conservative treatment. T1 and T2 pancreatic tumors are much more frequently resectable than are T3 and T4 tumors, and the 5-year survival rate for unresected T2, T3, and T4 cases is 0%. These findings emphasize the importance of early diagnosis of resectable pancreatic cancer. CA19-9 has shown satisfactory sensitivity in detecting advanced pancreatic cancer; we sought to determine the effectiveness of CA19-9 as part of a screening program for early cancer. Using elastase 1, CA19-9, and ultrasonography, we developed and tested a program of mass screening on persons presenting with and without abdominal complaints.

Adult↗
PubMed1994

Comparison of CA19-9 with other tumor markers in the diagnosis of cancer of the pancreas.

The carbohydrate antigen 19-9 (CA19-9) and radioimmunoassay have been shown to offer new hope for improving the diagnosis of pancreatic cancer, and various tumor markers (including SPan-1, DUPAN-2, and CA50) have been established. While clinical studies of these markers have found satisfactory sensitivities, only a few studies have compared these tumor markers on the same blood samples. We therefore evaluated the clinical efficacy of SPan-1, CA19-9, DUPAN-2, CA50, carcino-embryonic antigen, and Elastase 1 in detecting pancreatic cancer in identical blood samples.

Antigens, Neoplasm↗
PubMed1994

A novel mutation in the erythrocyte protein 4.2 gene of Japanese patients with hereditary spherocytosis (protein 4.2 Fukuoka).

Human erythrocyte protein 4.2 (band 4.2; pallidin) is a major membrane protein that comprises 5% of the total weight of the human erythrocyte membrane. Deficiencies of this protein have been observed in hereditary spherocytosis with anaemia, suggesting a role of protein 4.2 in erythrocyte stability and integrity. The molecular basis of this disorder remains unknown. As a first step in elucidating the pathogenesis of hereditary spherocytosis associated with protein 4.2 deficiency, we cloned and sequenced the erythrocyte protein 4.2 gene from a normal Japanese person. We prepared sets of oligonucleotide primers for polymerase chain reaction (PCR) and determined nucleotide sequences of exons and exon-intron boundaries of the protein 4.2 gene from three unrelated Japanese patients with hereditary spherocytosis due to a complete defect of protein 4.2, using PCR-related techniques. Two patients were homozygous for a missense mutation in codon 142 with the Ala (GCT)-->Thr (ACT) amino acid substitution that has been reported previously (protein 4.2NIPPON), whereas one patient was compound heterozygous for the same missense mutation in codon 142 and a guanine-adenine transition in codon 119 that changes the codon for Trp (TGG) to the termination codon (TGA) (protein 4.2Fukuoka). No additional mutation was identified in other exons of the protein 4.2 genes. Dot-blot hybridization with allele-specific oligonucleotide probes showed that homozygosity for the missense mutation in codon 142 and compound heterozygosity for the codon 142 and the codon 119 mutations were related to protein 4.2 deficiency in the families. Although two alleles of missense mutation of the codon 142 were also detected in 100 alleles of healthy Japanese, results obtained in this study indicate that the two mutations described above are closely related to the pathogenesis of hereditary spherocytosis due to protein 4.2 defect.

Adult↗
PubMed1994

Improvement of mitomycin C- and cyclophosphamide-induced thrombocytopenia and leucocytopenia by prior treatment with deoxyspergualin in dogs.

Deoxyspergualin (DGS) is a new immunosuppressant which has shown inhibitory haemopoietic activity. We investigated the myeloprotective effect of DSG against the haemopoietic injury of mitomycin C (MMC) or cyclophosphamide (CYC) by measuring peripheral blood cell numbers in dogs. DSG given at 5 mg/kg on days 3, 2 and 1 before, or at 10 mg/kg on either days 2 and 1 before or on day 1 before and the day of injection of MMC at 0.25 mg/kg ameliorated both the thrombocytopenia and leucopenia caused by MMC. This ameliorative effect was more evident on platelet counts than on white blood cell counts. In addition, the leucopenia and thrombocytopenia induced by a single injection of CYC at 10 mg/kg was also ameliorated by prior DSG administration. These findings suggest that DSG may be useful in protecting against the haemopoietic damage induced by chemotherapeutic agents in the treatment of cancer.

Animals↗
PubMed1994

Cellular composition of the pancreatic islets in Mongolian gerbils (Meriones unguiculatus).

In Mongolian gerbil, morphological changes with age in the content of endocrine cells in the pancreatic islets were analyzed and their relation evaluated by an oral glucose tolerance test. The glucose level 2 hours after glucose administration was 125 +/- 5 mg./d1 in the young group and 103 +/- 4 mg./d1 in the old group. In the dorsal portion, B cells were mainly observed in the central area of the islets, surrounded by circular layers of A cells in the peripheral area. Between the A cells and B cells, D cells were scattered or present in layers. A few PP cells were present in the peripheral area of the islets. In the ventral portion, only a few A cells were observed in the peripheral area of the islets, and B cells were surrounded by PP cells. Secretory granules of A cells generally had an electron-dense spherical core in the limiting membrane. The halo between the limiting membrane and core in A cells was narrower than that in B cells. Secretory granules of B cells were larger than those in A cells, and the core was less electron-dense, and the halo was wider. Secretory granules of D cells were similar in size to those of A cells; the core showed low electron density, and the halo was very narrow. Granules of PP cells resembled those of A cells, but the electron density of the core was slightly lower. The gerbils showed changes in glucose tolerance, the size of the pancreatic islets, the percentage of B cells, and of A cells in the dorsal portion with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

Efficacy of synchronized IMV on weaning neonates from the ventilator.

This study evaluated the efficacy of a new patient-triggered ventilator that triggered the patient's inspiratory effort by detecting the change in airflow by means of a 'hot wire' anemometer. This ventilator was used in both the conventional and the synchronized intermittent mandatory ventilation (SIMV) modes in seven neonates. Values for blood gas, spontaneous breathing rate, tidal volume of spontaneous breaths and minute volume were compared in all seven neonates. The resistive work of spontaneous breathing in five neonates, obtained with synchronized intermittent mandatory ventilation was compared with the values obtained using conventional mechanical ventilation on the previous day of weaning from the ventilator. At each the inflation time studied (0.4, 0.3, 0.24 s), all mechanical breath occurred synchronously with infants' inspiratory efforts. The median trigger delay was 80 ms. Oxygenation was improved on the new system compared with the conventional system. Tidal volume of spontaneous breathing and minute volume were increased with SIMV compared with conventional mechanical ventilation, although the resistive work of spontaneous breathing was decreased with SIMV. The tidal volume of spontaneous breaths was more constant with SIMV versus conventional mechanical ventilation. Thus, the airway flow-triggered SIMV may lessen inspiratory muscle fatigue during weaning process. We conclude that the SIMV is useful in weaning neonates from the ventilator.

Equipment Design↗
PubMed1994

Nitric oxide-mediated inhibitory response of rat proximal colon: independence from changes in membrane potential.

1. We studied the relation of nitric oxide-mediated relaxation of smooth muscle to changes in membrane potential of cells in the proximal colon of rats. 2. The resting membrane potential and electrical field stimulation (EFS)-induced junction potentials were recorded from the circular and longitudinal muscle cells. 3. Localized distension with a small balloon caused relaxation of the circular muscle on the anal side of the distended region (descending relaxation). Relaxation of the longitudinal muscle was also induced by EFS. 4. Inhibitory junction potentials (i.j.ps) were recorded from all circular muscle cells tested, but rarely from the longitudinal muscle cells. 5. The i.j.ps were recorded only in the presence of atropine but relaxations of both muscles were induced even in the absence of atropine. 6. Apamin (100 nM) completely abolished the i.j.ps recorded in both circular and longitudinal muscle cells, but had no significant effect on the relaxations of either. 7. In contrast to apamin, Ng nitro-L-arginine (10 microM) inhibited the relaxations of both muscles, but did not affect the i.j.ps. 8. Exogenously added nitric oxide (0.1-10 microM) induced relaxations of both muscles concentration-dependently, but did not affect the membrane potentials at these concentrations. 9. These data strongly suggest that nitric oxide-mediated relaxation of rat proximal colon is not associated with the i.j.ps of the cell membrane.

Animals↗
PubMed1994

Identification of nuclear factors that bind to the mouse tyrosinase gene regulatory region.

Several nuclear factors that interact with sequences in the 5' flanking region of the mouse tyrosinase gene were identified using band shift and methylation interference assays. One of these factors bind to an AT-rich sequence, TATCAATTAG, located at -183 base pairs upstream of the transcription start site. To isolate cDNA clone encoding this DNA binding protein, we have screened a lambda gt11 cDNA expression library prepared from mouse melanocyte cell line with a labeled oligonucleotide probe containing its binding site. Complementary DNA clones encoding mouse high mobility group protein HMG-I and its isoform HMG-Y were obtained. HMG-I(Y) is a low molecular size, basic nuclear protein that binds specifically to AT-rich region of double-stranded DNA in vitro. In Northern blot analysis the level of HMG-I(Y) mRNA expression did not correlate with that of tyrosinase or TRP-1. Although the amount of HMG-I(Y) transcripts has no apparent influence on the mouse tyrosinase gene expression, it is possible that HMG-I(Y) binds to the 5' flanking sequence of the tyrosinase gene as an auxiliary factor, and facilitates the binding and activity of other transcription factors.

Animals↗
PubMed1994

Endothelin-1 stimulates bile acid secretion and vesicular transport in the isolated perfused rat liver.

The effects of endothelin (ET) on portal pressure and bile secretion were examined using isolated perfused rat liver and rat hepatocyte preparations. ET-1 raised portal pressure dose dependently; administration at a high dose (10(-9) mol) induced a > 200% increase along with reduced bile flow and decreased secretion of bile acid and phospholipids. However, a low dose (10(-10) mol) of ET-1 brought about a < 100% portal pressure rise, enhanced both bile flow and excretion of bile acid and phospholipids, and significantly increased transfer of preadministered horseradish peroxidase (HRP) into bile. In addition, values for Ca2+ concentrations, examined by indo 1 fluorescence, were elevated in isolated hepatocytes after administration of ET-1. Papaverine suppressed the low-dose ET-1 stimulation effects on both portal pressure and bile secretion. Moreover, it also reduced the HRP excretion and suppressed intracellular Ca2+ release. This study demonstrated that ET-1 stimulates vesicular transport, probably via promotion of intracellular Ca2+ release, and, as a result, increases bile acid-dependent bile flow.

Animals↗
PubMed1994

Effect of protein derivatives on pancreatic secretion and release of secretin and CCK in rats.

We investigated the effect of intraduodenal administration of oligopeptide and a mixed amino acid solution, which contains the same amino acid composition as oligopeptide, on pancreatic exocrine secretion and the release of secretin and cholecystokinin (CCK). Anesthetized rats were prepared with pyloric ligation and cannulation of pancreatic duct and bile duct. Protein derivatives in three different doses (oligopeptide: 25, 100, and 400 mg/h; and mixed amino acid solution: 70, 140, and 280 mg/h, pH 7.0) were infused into the duodenum for 1 h. Pancreatic juice was collected, and plasma concentrations of secretin and CCK were measured by radioimmunoassay. In addition, the effect of intravenous injection of an antisecretin serum or a CCK antagonist, loxiglumide, on pancreatic secretion stimulated by oligopeptide or mixed amino acid solution was also studied. Oligopeptide produced a significant dose-related increase in pancreatic secretion including volume, HCO3-, amylase, and trypsin output, plasma secretin (r = 0.792, P < 0.001), and plasma CCK (r = 0.421, P < 0.01). Similarly, mixed amino acid solution produced a dose-related increase in pancreatic juice volume, HCO3-, amylase, and trypsin output. Compared with CCK, the percentage increase in plasma secretin was 7.3x and 2.8x higher in response to oligopeptide (400 mg/h) and mixed amino acid solution (280 mg/h), respectively. An antisecretin serum almost completely inhibited volume flow and HCO3- output stimulated by oligopeptide as well as mixed amino acid solution, but not amylase and trypsin output. In contrast, loxiglumide significantly suppressed amylase and trypsin output stimulated by protein derivatives, but did not affect volume flow or HCO3- output.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1994

Descending pathways of powerful pressor response elicited by suprapontine cerebral ischemia in rabbits.

We determined the magnitude of the pressor and sympathoexcitatory responses elicited by suprapontine cerebral ischemia (SCI) and the descending pathways in the rostral medulla mediating them. The suprapontine structures of anesthetized and artificially ventilated rabbits were selectively exposed to cerebral ischemia, by combined occlusions of basilar and common carotid artery. SCI produced a pressor response of 78 +/- 9 (SE) mmHg and an increase in renal sympathetic nerve activity of 289 +/- 21% compared with preischemic levels. The magnitude of the pressor and sympathoexcitatory response to SCI was comparable to those in response to global cerebral ischemia. Microinjection of the neurotoxin kainic acid into the pressor sites of the rostral ventrolateral medulla significantly (P < 0.05) reduced the SCI pressor response to 34 +/- 11% of the prelesion control response. Chemical lesions of the pressor sites in the rostral medial and ventromedial medulla resulted in a significant decrease in the pressor response to SCI to 78 +/- 12% of the control response. These results indicate that the suprapontine structures play an important role in the generation of the powerful pressor response elicited by cerebral ischemia and that the pressor response to SCI is mediated by pressor neurons in the rostral medulla.

Animals↗
PubMed1994

Cognitive functions in subjects with incidental cerebral hyperintensities.

We investigated the association between incidental cerebral hyperintensities (CH) found by magnetic resonance imaging (MRI) and cognitive functions in neurologically normal, nondemented subjects. Semiquantitative scores for MRI lesions and those for brain atrophy were compared with the results of extensive cognitive examinations using multivariate analysis. There was no correlation between CH and cognition, except that periventricular hyperintensities, especially those in posterior locations, were associated with reduced performance in the Stroop test. Overall cognitive functions were associated with age, and age was a predominant factor in the prefrontal functions. Brain atrophy was associated more with decline of the posterior and dorsolateral frontal brain functions. We suggest that disturbances in attention and speed may initially result from incidental CH, while other cognitive functions remain unaffected.

Adult↗
PubMed1994

Laboratory-documented hallucination during sleep-onset REM period in a normal subject.

During an experiment on nocturnal sleep interruption, we observed a unique case of hallucination without sleep paralysis during the sleep-onset REM period in a normal individual. We documented the polysomnogram recorded during this hallucination. The polysomnogram showed a mixed pattern of Stages REM and W, with muscle-tone inhibition, rapid eye movements (REMs), slow eye movements (SEMs), and abundant alpha EEG trains. The blocking of alpha EEG trains by REMs appeared to reflect visual processing similar to that which occurs during waking. This hallucination was distinct from ordinary sleep-onset mentation in that it included strong emotional components and in that the subject simultaneously experienced both hallucinatory mentation and reality contact. This hallucination may resemble sleep paralysis with regard to its physiological and psychological background, and the discrimination of these two phenomena may depend on the subject's own awareness of muscle-tone inhibition.

Adult↗
PubMed1994

Age-dependent decreases in fibrinolytic enzyme activities in serum of healthy subjects.

We investigated the age-dependency of serum levels of 9 kinds of proteases. The results showed that the enzymatic activities corresponding to urokinase, plasmin, and thrombin, all involved in blood clotting and fibrinolysis, were inversely correlated with age. This suggests that there is some similarity between the normal process of aging and the pathologic process of Alzheimer's disease. Compared with our previous data on Alzheimer patients, the present results indicate that some derangement in the aging process is involved in the pathogenetic mechanisms of Alzheimer's disease.

Aging↗
PubMed1994

Phenotypic reversion induced by anthracyclines in ras oncogene-expressed cells; structure-activity relationships.

Several antitumor anthracyclines, including those in preclinical stages, were examined for their action in reversing tumorous phenotypes of H- or K-ras 3T3 cells (NIH3T3 cells transformed by human H- or K-ras oncogene) into normal phenotypes, such as flattened cell morphology, anchorage dependent cell growth, etc. (referred to as anti-ras activity). The study elucidated relationships between the chemical structure of anthracyclines and the anti-ras activity. The human tumor cell line T24, which has a mutated H-ras gene, responded to the anthracyclines, as did K- or H-ras 3T3 cells, in respect to the phenotypic alterations. Pirarubicin was more than 4 times as active as aclarubicin in inhibiting the growth of solid tumors of K-ras 3T3 cells in nude mice, possibly reflecting a difference in anti-ras activity between the two antibiotics.

3T3 Cells↗