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Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 307 records · Page 17Linked to original sources
PubMed1999

Kex2 family endoprotease furin is expressed specifically in pit-region parietal cells of the rat gastric mucosa.

The proprotein-processing endoprotease furin is localized in the gastric epithelial cells of the pit region in the rat gastric gland. The gastric pit is composed of several cell types, including gastric surface mucosal (GSM) cells and parietal cells. Furin converts many growth- or differentiation-related proproteins to their active forms. We examined identification of furin-positive cells by immunostaining of rat gastric mucosa and regulators of the furin expression by measuring the furin promoter activity by luciferase assay. Furin-positive cells were stained for H(+)-K(+)-ATPase, indicating that they are parietal cells. Furin-positive parietal cells were not stained for transforming growth factor-alpha (TGF-alpha) but were surrounded by TGF-alpha-positive GSM cells. In contrast, parietal cells below the proliferative zone were positive for TGF-alpha but not for furin. Furin-positive parietal cells expressed a high level of epidermal growth factor receptor (EGFR). TGF-alpha stimulated the furin promoter activity highly in a mouse GSM cell line GSM06. Thus we suggest that the parietal cells of the pit region have furin-mediated functions that can be stimulated by EGFR signaling.

Animals↗
PubMed1999

Gastrin stimulates the growth of gastric pit with less-differentiated features.

Gastrin stimulates the growth of gastric mucosa by increasing mostly its glandular region but is not known to induce the growth of a pit region where its major constituent cells, gastric surface mucous (GSM) cells, turn over rapidly. To investigate the effect of gastrin on GSM cells, we generated hypergastrinemic mice by expressing a human gastrin transgene. We obtained a hypergastrinemic mouse line whose average serum gastrin level is 671 +/- 252 pg/ml (normal level <150 pg/ml). Gastrin-positive cells were found in the fundic mucosa. The gastric mucosa exhibited hypertrophic growth, which was characterized by an elongated pit with an active proliferative zone, but the glandular region containing parietal cells was normal or reduced in size. The GSM cells contained fewer mucous granules than those of control littermates and lost reactivity to the GSM cell-specific cholera toxin beta-subunit lectin. GSM cells along the foveolar region and many mucous neck cells became Alcian blue positive, suggesting the appearance of sialomucin in these cells. We suggest that gastrin stimulates the growth of the proliferative zone of gastric glands, which results in the elongation of the pit region whose GSM cells exhibit less-differentiated features.

Animals↗
PubMed1999

Potentiation of carbachol-induced amylase release by propionate in guinea pig and vole pancreatic acini.

The action of propionate, one of the major end products of microbial fermentation in herbivores was investigated in isolated, perifused pancreatic acini of guinea pigs, voles, and mice. With the use of guinea pig acini, 100 microM propionate had no effect, whereas 300 and 600 microM increased amylase release by six- and ninefold, respectively. Simultaneous perifusion of carbachol (CCh) 10 microM plus propionate 100 microM in guinea pig acini produced a potentiated secretory response that was 130% higher than the summated value obtained with CCh and propionate alone. The potentiation by propionate (100 microM) of CCh (10 microM)-induced amylase release was also obtained in vole pancreatic acini, but the mouse pancreatic preparation did not exhibit a similar potentiation. In contrast to CCh, propionate (100-600 microM) alone had no significant effect on intracellular Ca2+ concentration ([Ca2+]i) and did not alter [Ca2+]i elicited by CCh. Ca ionophore A23187 (5 microM)-induced amylase release in guinea pig acini was enhanced twofold by the addition of propionate. Cellular cAMP content was increased slightly by propionate, but did not alter dose dependently. The cAMP level with combinations of CCh and propionate was almost same as that with CCh alone and propionate alone. Staurosporine did not modify amylase secretion induced by a combination of CCh and propionate. These results suggest that propionate, in addition to a direct action on amylase release, potentiates CCh-induced amylase release in guinea pig and vole acini via a secretory pathway not associated with an increase in [Ca2+]i and cellular cAMP.

Amylases↗
PubMed1999

Incorporation of dietary docosahexaenoic acid into the central nervous system of the yellowtail Seriola quinqueradiata.

In order to show the involvement of docosahexaenoic acid (DHA) in the development of the central nervous system (CNS) in carangid fish, we conducted tracer experiments by feeding radioactive DHA to larval yellowtail (Seriola quinqueradiata). Artemia nauplii were enriched with 14C-labeled DHA and fed to larval yellowtail for eight or ten days. Autoradiography of frozen sections, using both electric imaging plates and X-ray sensitive film, clearly showed that DHA was incorporated into and retained in the brain, spinal cord, and eyes. The brain, eyes, gill raker, liver, guts, and other muscle and bone structures were dissected, and radioactivity was measured in each organ by liquid scintillation counter. The results of this study suggest the incorporation of DHA into the brain. Considering our previous results indicating that DHA-free fish cannot form schools, we conclude that the incorporation of DHA into the brain might be a critical factor in the ontogeny of schooling behavior.

Animals↗
PubMed1999

Characteristic transfer of colostral components into cerebrospinal fluid via serum in neonatal pigs.

In order to evaluate the possibility of modification of brain function by colostral suckling, the characteristic transfer of colostral components into serum and cerebrospinal fluid (CSF) has been studied by SDS electrophoresis, immunoblot and ELISA methods in nonsuckling pigs. Total protein concentrations in the serum increased immediately after oral administration of bovine colostrum, reaching a peak value (7.0 +/- 0.7 g/dl) at 24 h after administration, corresponding to a 3-fold increase compared to preinfusion levels. IgG and other macromolecular components (MW 19, 000-58,000) were recognized in serum by electrophoretic and ELISA analysis. Total protein concentrations in the CSF collected from the cisterna magna also increased steeply after colostral administration, reaching a maximal value (54.1 +/- 5.0 mg/dl) at 4 h, corresponding to a 4-fold increase compared to preinfusion levels. Two colostral components (MW 19,000 and 31,000) in serum were confirmed to be present in the CSF by electrophoresis. The component of MW 19,000 was identified by immunoblot as beta-lactoglobulin. IgG in serum transferred from colostrum could not be detected in the CSF by ELISA. Lactoferrin administered into the intestine was also detected in the CSF via serum. These results indicate that some components of colostrum can be transported into the CSF via the serum, suggesting the possibility of modification of immature brain functions by colostral suckling in neonatal pigs.

Animals↗
PubMed1999

Conjunctival epithelium expression of HLA-DR in dry eye patients.

PURPOSE: To compare conjunctival epithelium expression of HLA-DR and ICAM-1 with tear dynamics and ocular surface parameters. METHODS: Brush cytology and flow cytometry were used to quantitatively analyze HLA-DR and ICAM-1 expression in 28 dry eye patients. RESULTS: HLA-DR was expressed in 66% of the conjunctival cells of dry eye patients. This expression correlates with that of ICAM-1, as well as with the Schirmer test results (p < 0.05). CONCLUSION: This study confirmed that dry eye consists not only of ocular surface desiccation, but also of upregulation of the HLA-DR and ICAM-1 molecule in the conjunctival epithelium, possibly resulting in increased inflammation.

Antibodies, Monoclonal↗
PubMed1999

Removal and inactivation of hepatitis B virus from contaminated pooled plasma in a large-scale manufacturing process for factor VIII and human serum albumin.

BACKGROUND AND OBJECTIVES: The Japanese Red Cross Society recalled one lot of monoclonal-antibody-purified factor VIII (F VIII) and two lots of human serum albumin (HSA) 5 months after preparation of the final products, because of a procedural error that led to contamination by a unit of plasma positive for hepatitis B surface antigen (HBsAg). We evaluated the effectiveness of virus inactivation/removal in a large-scale process for manufacturing F VIII and HSA. MATERIALS AND METHODS: HBV DNA in the retained samples in process was measured by the polymerase chain reaction (PCR). The kinetics of virus inactivation by solvent-detergent (S/D) treatment was examined using model viruses. We also did a look-back survey of the patients who received corresponding products. RESULTS: Contaminated hepatitis B virus (HBV) DNA became undetectable beyond fraction S IV-I in the albumin process and immunoaffinity chromatography in the F VIII process, respectively. The model viruses were inactivated within 5 s by S/D treatment. There is no evidence that patients were infected by HBV after transfusion of these products. CONCLUSION: We conclude that virus inactivation/removal was effectively achieved in a large-scale manufacturing process for F VIII and HSA.

Factor VIII↗
PubMed1999

A mutation in the insulin 2 gene induces diabetes with severe pancreatic beta-cell dysfunction in the Mody mouse.

The mouse autosomal dominant mutation Mody develops hyperglycemia with notable pancreatic beta-cell dysfunction. This study demonstrates that one of the alleles of the gene for insulin 2 in Mody mice encodes a protein product that substitutes tyrosine for cysteine at the seventh amino acid of the A chain in its mature form. This mutation disrupts a disulfide bond between the A and B chains and can induce a drastic conformational change of this molecule. Although there was no gross defect in the transcription from the wild-type insulin 2 allele or two alleles of insulin 1, levels of proinsulin and insulin were profoundly diminished in the beta cells of Mody mice, suggesting that the number of wild-type (pro)insulin molecules was also decreased. Electron microscopy revealed a dramatic reduction of secretory granules and a remarkably enlarged lumen of the endoplasmic reticulum. Little proinsulin was processed to insulin, but high molecular weight forms of proinsulin existed with concomitant overexpression of BiP, a molecular chaperone in the endoplasmic reticulum. Furthermore, mutant proinsulin expressed in Chinese hamster ovary cells was inefficiently secreted, and its intracellular fraction formed complexes with BiP and was eventually degraded. These findings indicate that mutant proinsulin was trapped and accumulated in the endoplasmic reticulum, which could induce beta-cell dysfunction and account for the dominant phenotype of this mutation.

Alleles↗
PubMed1999

Stimulation of cellular XTT reduction by cytochrome oxidase inhibitors.

XTT reducing activity by CHO and L1210 cells was found to be stimulated by the presence of cytochrome oxidase inhibitors such as NaN3 or KCN. Among the other respiratory chain inhibitors, antimycin A (a complex III inhibitor) and chlorpromazine inhibited cellular XTT reduction, and rotenone and malonate showed slight inhibition and no effect, respectively. It is suggested that XTT reduction is coupled with the respiratory chain via cytochrome c, which is located between complexes III and IV (cytochrome oxidase).

Animals↗
PubMed1999

Futalosine and its derivatives, new nucleoside analogs.

Futalosine, a new nucleoside analog, was isolated from a fermentation broth of Streptomyces sp. MK359-NF1. Some chemical derivatives of futalosine were prepared. 6-O-Methylfutalosine methylester inhibited growth of HeLa-S3 cells in vitro (IC50 = 19.5 micrograms/ml) in contrast to the weak activity of futalosine. 6-O-Methylfutalosine methylester at concentrations higher than 10 micrograms/ml inhibited incorporation of 3H-TdR and 3H-UR but not 3H-Leu in the acid-soluble fractions of HeLa-S3 cells.

Antibiotics, Antineoplastic↗
PubMed1999

Sequential changes of hepatocyte growth factor in the serum and enhanced c-Met expression in the myocardium in acute myocardial infarction.

A 68-year-old male with acute myocardial infarction (AMI) was admitted to the hospital with chest pain that had started 1 day earlier. The serum levels (ng/ml) of hepatocyte growth factor (HGF) were 1.06, 1.22, 1.05, 0.72 and 0.64 on days 2, 3, 4, 5 and 6 postinfarction, respectively. He died suddenly due to cardiopulmonary arrest on day 6. At autopsy, approximately 400 ml of bloody pericardial fluid, caused by rupture of the left ventricle, was detected and the c-Met expression in the myocardium was immunohistochemically found to be most intense in the border zone of the infarcted and non-infarcted region. Although there was no c-Met expression in the infarcted myocardium, it was increased in the myocardial cells surrounding the blood vessels. This is the first report to show sequential changes of HGF in the serum, as well as c-Met expression in the myocardium, in a patient with AMI.

Aged↗
PubMed1999

Early occurrence of respiratory muscle deoxygenation assessed by near-infrared spectroscopy during leg exercise in patients with chronic heart failure.

The mechanisms of respiratory muscle deoxygenation during incremental leg exercise with expired gas analysis were investigated in 29 patients with chronic heart failure and 21 normal subjects. The deoxygenation and blood volume of the respiratory muscle and exercising leg muscle were assessed by near-infrared spectroscopy (NIRS). To evaluate the influence of the leg exercise on the blood volume of the respiratory muscle, 10 normal subjects also underwent a hyperventilation test with NIRS. The respiratory muscle deoxygenation point (RDP), at which oxygenated hemoglobin starts to decrease, was observed in both groups during exercise. The oxygen consumption (VO2) and the minute ventilation at the RDP in the patients was lower (p<0.01). At the same VO2, the respiratory rate was higher in patients (p<0.01). During exercise, the blood volume of the leg muscle increased, while that of the respiratory muscle decreased. During a hyperventilation test, the minute ventilation was higher than that of the RDP during exercise, the blood volume of the respiratory muscle did not decrease, and the RDP was not detectable. In conclusion, a limited ability to increase perfusion of respiratory muscles during exercise combined with the greater work of breathing results in early respiratory muscle deoxygenation in patients with chronic heart failure.

Blood Volume↗
PubMed1999

Apoptosis of villous epithelial cells and follicle-associated epithelial cells in chicken cecum.

The process of the disappearance of epithelial cells was examined in chicken cecal villi and follicle-associated epithelium (FAE). The apoptotic epithelial cells with intense DNA-fragmentation and their exfoliation were found in the villous tips. The epithelial cells with weak DNA-fragmentation were seen in the upper portion of the villi and their sparse exfoliations were also found there. Numerous epithelial cells in the intestinal lumen expressed the apoptotic features. A row of apoptotic epithelial cells with DNA-fragmentation was also found in the apical FAE, whereas no M cells exhibited any apoptotic signs. In all cecal regions, CD3+, CD8+, and TCR2+ lymphocytes were predominant in the epithelium at the upper portion of the villi and the FAE. CD4+ lymphocytes were mainly seen in the lamina propria. TCR1+ lymphocytes were not abundant in comparison with TCR2+ lymphocytes in the epithelium. TCR3+ T lymphocytes were rarely detected. These results suggest that the chicken cecal epithelial cells exfoliated into the lumen after the induction of the apoptosis, and that the induction may be involved with CD3+, CD8+, and TCR2+ lymphocytes. No death in M cells suggests that M cells may transform into microvillous epithelial cells.

Animals↗
PubMed1999

Mediators of nonadrenergic, noncholinergic relaxation in longitudinal muscle of the intestine of ICR mice.

Mediators of nonadrenergic, noncholinergic (NANC) relaxation in longitudinal muscle of several regions of ICR mouse intestine were studied. An inhibitor of synthesis of nitric oxide, N(G)-nitro-L-arginine (L-NOARG) at 10 microM significantly inhibited NANC relaxations induced by electrical field stimulation (EFS) in the jejunum, ileum, and the proximal and distal colon. Especially in the ileum extent of the inhibition was more than 80%. An antagonist of vasoactive intestinal peptide (VIP) receptors, VIP(10-28) at 3 microM partially inhibited the EFS induced relaxations in the jejunum and proximal colon, but very slightly in the distal colon and had no effect in the ileum. An antagonist of pituitary adenylate cyclase activating peptide (PACAP) receptor, PACAP(6-38) at 3 microM partially inhibited the EFS-induced relaxations in the proximal and distal colon, but not in the jejunum and ileum. Totals of the percentages of relaxant components mediated by nitric oxide, VIP and PACAP in every region are roughly equal to a hundred percent. In another series of experiments, EFS-induced relaxations were almost completely inhibited by the treatment of the segments with L-NOARG and VIP(10-28) in the jejunum, with L-NOARG, VIP(10-28) and PACAP(6-38) in the proximal colon, and with L NOARG and PACAP(6-38) in the distal colon. The present results suggest that nitric oxide solely mediates the relaxation of longitudinal muscle of the ileum of ICR mice, whereas nitric oxide and VIP co-mediate it in the jejunum, nitric oxide, VIP and PACAP in the proximal colon, and nitric oxide and PACAP in the distal colon.

Animals↗
PubMed1999

Application of an in situ PCR hybridization method to detection of human T-lymphotropic virus type I-infected cells in the lung.

We applied an in situ polymerase chain reaction (PCR) hybridization method in order to detect human T-lymphotropic virus type I-infected cells in routinely-processed paraffin sections of the lung from 13 autopsied patients with adult T-cell leukemia (ATL). Previously reported protocol resulted in somewhat non-specific staining in our sections. Therefore, we used a hot start PCR method using specialized commercially-available polymerase in order to increase the specificity. Of 6 patients with ATL cell invasion into the lungs, 4 exhibited strong positive staining of almost all invading ATL cells. In contrast, 7 patients without ATL cell invasion into the lungs did not demonstrate any significant reactivity. Since the method described here is a relatively simple hot start method and does not yield false-positives, it may allow us to determine whether human T-lymphotropic virus type I (HTLV-I) associated disorders are related to lymphocytes integrating the HTLV-I genome.

Adult↗
PubMed1999

Development of resistance to chloroform toxicity in male BDF1 mice exposed to a stepwise increase in chloroform concentration.

To investigate the development of resistance to chloroform toxicity, a 4-week inhalation study was conducted in which BDF1 male mice were exposed to a low level of chloroform for an initial two-week period, and thereafter the exposure concentration was increased for a second two-week period. The animals were exposed to inhalation of chloroform vapor 6 hr per day, 5 days per week, with clinical observation and measurement of body weight conducted. These results demonstrate that pre-exposure to chloroform at a low dose level induced resistance to a higher dose of chloroform in male mice. This resistance was dependent on the pre-exposure concentration.

Animals↗