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Biomedical subjects

K Takeuchi

Publications and source records attributed to K Takeuchi.

At least 505 records · Page 28Linked to original sources
PubMed1997

Analysis of pathogenic elements involved in gastric lesions induced by non-steroidal anti-inflammatory drugs in rats.

Pathogenesis of gastric damage induced by non-steroidal anti-inflammatory drugs (NSAID) involves multiple elements, such as deficiency of prostaglandins (PG), gastric hypermotility, neutrophil activation and luminal acid. The present study was performed to examine the effects of these elements, either alone or in combination, on the rat gastric mucosa and investigate which element is most closely associated with the gastric ulcerogenic response to NSAID. The following treatments were used to express various pathogenic elements: (i) a low dose of indomethacin (IM) to cause PG deficiency; (ii) 2-deoxy-D-glucose (2DG) to induce gastric hypermotility and acid secretion; (iii) histamine to induce acid hypersecretion; and (iv) n-formyl-Met-Leu-Phe (fMLP) to elicit neutrophil activation. When rats fasted for 18 h were subjected to each treatment alone, only 2DG caused slight macroscopic damage in the gastric mucosa within 4 h. Indomethacin showed over 90% inhibition of mucosal PG generation and fMLP increased myeloperoxidase activity four-fold greater than normal values, yet either of these treatments alone did not cause any damage in the stomach. However, the combination of IM with 2DG or His provoked severe lesions in the stomach or the duodenum, respectively, while fMLP did not modify or potentiate the mucosal ulcerogenic response to other treatments. We conclude that among various pathogenic elements only gastric hypermotility is sufficient, by itself, to induce mild damage in the mucosa, that PG deficiency may be critical in the increase of mucosal susceptibility to injury and that neutrophil activation alone is not ulcerogenic in the gastric mucosa nor does it potentiate the ulcerogenic effect of other elements. Luminal acid may be a prerequisite for later extension of damage to severe lesions.

Animals↗
PubMed1997

Laterality of finger movements in preterm infants.

The laterality of head position, spontaneous finger movements, hand-face contact, and hand-mouth contact was studied in low-risk preterm infants of 31 to < 37 weeks postconceptional age (intrauterine + neonatal period at time of study). The head was predominantly turned towards the right side during the preterm period. Hand-mouth contact was more frequent on the right side and coincided well with the side to which the head was turned. Other hand movements, too, were more frequent on the right side than on the left, but these were also seen in the fingers contralateral to the direction in which the head was turned. These findings suggest that even before birth a spontaneous preference for head position is present and is already associated with asymmetry in coordinated finger movements.

Age Factors↗
PubMed1997

PACAPs stimulate duodenal bicarbonate secretion at PACAP receptors in the rat.

We investigated the effects of pituitary adenylate cyclase-activating polypeptides (PACAPs) on gastroduodenal HCO(3)- secretion in anesthetized rats and characterized their effects by comparison with the effects of vasoactive intestinal polypeptide (VIP). Under urethan anesthesia, a rat proximal duodenal loop or a rat stomach mounted in an ex vivo chamber (in the absence of acid secretion) was perfused with saline, and HCO(3)- secretion was measured at pH 7.0 using a pH-stat method and by addition of 10 mM HCl. Intravenous injection of PACAP-27 stimulated HCO(3)- secretion in a dose-dependent manner in the duodenum, but not in the stomach, although this peptide had no effect on duodenal HCO(3)- secretion after intracisternal administration. The duodenal HCO(3)- stimulatory action was similarly observed after intravenous administration of PACAP-38 and VIP, and the potency of action was in the following order: PACAP-27 > PACAP-38 = VIP. The duodenal HCO(3)- stimulatory action of PACAP-27 was potentiated by pretreatment with 3-isobutyl-1-methylxanthine, similar to that of prostaglandin E2, and was significantly attenuated by PACAP-(6--27) (PACAP antagonist) or Ac-Tyr1,D-Phe2-VIP (VIP antagonist) but was not affected by bilateral vagotomy or prior administration of atropine, verapamil, and indomethacin. Forskolin, the stimulator of adenylate cyclase, also increased HCO(3)- secretion in the duodenum, but not in the stomach. These results suggest that 1) PACAP is a potent stimulator of HCO(3)- secretion in the duodenum, but not in the stomach, and may be involved in the peripheral regulation of duodenal HCO(3)- secretion, 2) this action is mediated by adenosine 3',5'-cyclic monophosphate, probably through PACAP and VIP receptors, and 3) adenosine 3',5'-cyclic monophosphate is a mediator in duodenal, but not in gastric, HCO(3)- secretion.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Alteration in water channel AQP-2 by removal of AVP stimulation in collecting duct cells of dehydrated rats.

Dehydration increased the expression of aquaporin of collecting duct (AQP-2) and translocated AQP-2 to the apical plasma membranes from cytoplasmic vesicles of collecting duct cells. We determined whether the abrupt decrease in circulating arginine vasopressin (AVP) by giving excess water affects the expression of AQP-2 mRNA and subcellular localization of AQP-2 in collecting duct cells of the dehydrated rats. The 72-h water deprivation increased plasma AVP levels to 3.1 pg/ml and the expression of AQP-2 mRNA by 336% in rats, which were concomitantly abolished by the 40 ml/kg oral water load. A 50% inhibition ofAQP-2 mRNA expression was obtained with 20 min after the forced water load. In immunohistochemistry and electron microscopy, the AQP-2 was manifestly present around the apical edge of collecting duct cells in the 72-h dehydrated rats. The AQP-2 was diffusely translocated into the cytoplasm 1 h after the forced water administration. These results indicate that AVP plays the on-off regulation of AQP-2 mRNA expression and that a majority of AQP-2 is regulated by the shuttle recycling in the collecting duct cells.

Animals↗
PubMed1997

Salt loading enhances rat renal TxA2/PGH2 receptor expression and TGF response to U-46,619.

The tubuloglomerular feedback (TGF) response is potentiated by thromboxane A2 (TxA2) and/or prostaglandin endoperoxide (PGH2) acting on specific receptors. Infusion of the TxA2/PGH2 mimetic, U-46,619, into conscious rats leads to hypertension that is potentiated by a high-salt intake. Therefore, we tested the hypothesis that a high-salt intake enhances the expression of transcripts for TxA2/PGH2 receptors in the kidney and glomeruli and enhances the response of TGF to TxA2/PGH2 receptor stimulation. Groups of rats were accommodated to a low-salt (LS), normal salt (NS), or high-salt (HS) diet for 8-10 days. TxA2/PGH2 receptor mRNA was detected by reverse transcription-polymerase chain reaction in kidney cortex, isolated glomeruli, and abdominal aorta. TxA2/PGH2 mRNA abundance was significantly (P < 0.001) increased during intake of high-salt compared with low-salt diets in the kidney cortex (1.34 +/- 0.10 vs. 0.84 +/- 0.04 arbitrary units) and isolated outer cortical glomeruli (0.68 +/- 0.04 vs. 0.32 +/- 0.03 arbitrary units), but there was no effect of salt on TxA2/PGH2 receptor mRNA expression in the aorta. Maximal TGF responses were assessed from the increase in proximal stop flow pressure (an index of glomerular capillary pressure) during increases in loop of Henle perfusion with artificial tubular fluid from 0 to 40 nl/min. Compared with vehicle, the enhancement of maximal TGF with U-46,619 (10(-6) M) added to the perfusate was greater in rats adapted to high-salt than normal salt (HS: +9.6 +/- 1.1 vs. NS: +5.1 +/- 0.4 mmHg; P < 0.001) or low-salt (LS: +3.8 +/- 1.3 mmHg; P < 0.001) intakes. Responses to U-46,619 at each level of salt intake were blocked by > 70% by the TxA2/PGH2 receptor antagonist ifetroban. In contrast, enhancement of TGF by peritubular capillary perfusion of arginine vasopressin (AVP; 10(-7) M) was similar in high-salt and low-salt rats (HS: +1.5 +/- 0.6 vs. LS: +1.6 +/- 0.5 mmHg; not significant). We conclude that salt loading increases selectively the abundance of TxA2/PGH2 receptor transcripts in the kidney cortex and glomerulus, relative to the aorta, and enhances selectively TGF responses to TxA2/PGH2 receptor activation but not to AVP.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Simultaneous lung and liver resection for primary pulmonary leiomyosarcoma.

We report on a patient with primary pulmonary leiomyosarcoma and hepatic metastasis who was treated successfully with a single-stage surgical operation. As a cure for primary pulmonary leiomyosarcoma has only been achieved by surgical resection, primary radical treatment should be considered, even in advanced cases having distant metastases which are expected to be resectable.

Humans↗
PubMed1997

Role of nitric oxide in mucosal blood flow response and the healing of HCl-induced lesions in the rat stomach.

The role of nitric oxide (NO) in the gastric mucosal blood flow response and the healing of HCl-induced gastric lesions was investigated in rats. After 18 h fasting rats were given 0.6 N HCl p.o. for the induction of gastric lesions, and 1 h later they were fed normally. After induction of gastric lesions, they were repeatedly administered the NO synthase inhibitors NG-nitro-L-arginine methyl ester (L-NAME 5-20 mg/kg p.o. twice daily) or aminoguanidine (20 mg/kg s.c. once daily) for 7 days. Gastric lesions caused by HCl healed almost completely within 5 days with granulation and to an extent with re-epithelialization. Repeated administration of L-NAME but not aminoguanidine significantly delayed the healing of gastric lesions in a dose-dependent manner. The damaged mucosa secreted less acid, but showed a marked rise in H+ permeability, resulting in luminal acid loss accompanied by an increase of mucosal blood flow. Aminoguanidine did not significantly affect any of these functional changes observed in the stomach after damage by HCl, whereas L-NAME treatment slightly reversed the decreased acid response, increased the luminal H+ loss, and totally inhibited the mucosal hyperemic response associated with luminal acid loss in the damaged mucosa. In addition, the deleterious influences of L-NAME on the mucosal blood flow response and the healing of gastric lesions were significantly antagonized by co-administration of L-arginine but not of D-arginine (500 mg/kg x 2, i.p.). Luminal output of NO2-/NO3- was significantly increased in pylorus-ligated stomachs in control rats on days 3 and 5 after damage, and such increases in gastric NO output were completely attenuated by L-NAME treatment. These results suggest that endogenous NO may contribute to the healing of acute gastric injury by mediating the mucosal hyperemic responses associated with acid back-diffusion and by facilitating acid disposal in the damaged mucosa. NO mediating such responses and participating in the healing aspect of gastric lesions may be produced by the constitutive type of NO synthase.

Animals↗
PubMed1997

The Watanabe heritable hyperlipidemic rabbit is a suitable experimental model to study differences in tissue response between intimal and medical injury after balloon angioplasty.

The study evaluates whether the Watanabe heritable hyperlipidemic (WHHL) rabbit is an adequate model to study mechanisms that underlie differences in tissue response after postangioplasty injury. Postangioplasty studies of human coronary arteries have revealed that healing and restenotic processes differ depending on whether the laceration is limited to the atherosclerotic plaque or whether injury extends into the media. Forty-five homozygous WHHL rabbits underwent percutaneous transluminal angioplasty of the left subclavian artery. The inflated arterial segment was studied histologically at 3, 7, 14, 28, and 56 days, using conventional and immunohistochemical techniques to identify macrophages, smooth muscle cell (SMC) phenotypes, and cell proliferation. Electron microscopy was done to study reendothelialization. There were marked differences in response between those segments with medial injury and those with injury limited to the atherosclerotic plaque tissues. The latter category shows a distinct retardation in redifferentiation of SMCs, confirming previous observations in human coronary arteries. In these segments, moreover, cell proliferation occurred mainly in macrophages and spindle cells. Medial injury showed a more florid fibrocellular response, as in human coronary arteries, with cell proliferation initially confined to areas with dedifferentiated SMCs in the preexistent media and, once neointimal tissue was formed, among spindle cells also. The similarities with the repair processes encountered in postangioplasty human coronary arteries suggest that the WHHL rabbit is an adequate model to study differences in the response related to different types of angioplasty injury.

Angioplasty, Balloon↗
PubMed1997

Efficient expression of mono- and diacylglycerol lipase gene from Penicillium camembertii U-150 in Aspergillus oryzae under the control of its own promoter.

The gene, mdlA, coding for mono- and diacylglycerol lipase from Penicillium camembertii U-150 was expressed efficiently in Aspergillus oryzae under the control of its own promoter. The gene product was secreted into the culture medium with a highest productivity of 1 g/liter and correctly processed at both N- and C-termini. KEX2-like processing was suggested to occur at the C-terminus in both A. oryzae and P. camembertii. Specific activity and substrate specificity of the purified recombinant protein were also almost the same to that of native protein but the extent of N-glycosylation in the recombinant protein was about half of that of the native protein. The presence of introns did not seem to affect the gene expression. The mdlA expression was induced by lipids and regulated transcriptionally in A. oryzae as well as P. camembertii. Promoter deletion analysis showed that the region between the positions at -382 and -554 bp from the translation initiation point was important to the higher expression of mdlA. The promoter sequence of mdlA was compared to that of the Geotrichum candidum lipase gene, which is also reported to be inducible by lipids, with three commonly observed oligonucleotide sequences.

Aspergillus oryzae↗
PubMed1997

Three cases of Gitelman's syndrome possibly caused by different mutations in the thiazide-sensitive Na-Cl cotransporter.

Three adult Japanese cases of Gitelman's syndrome were characterized by secondary aldosteronism, hypokalemic alkalosis, hypomagnesemia, and hypocalciuria. Two were revealed to be familial cases. A mutation in the thiazide-sensitive Na-Cl cotransporter gene, which had already been confirmed in one family (Takeuchi et al. J Clin Endocrinol Metab 81: 4496,1996), was not detected in the other two cases. These observations may possibly support the previous report (Simon et al. Nature Genet 12: 24, 1996) that Gitelman's syndrome is caused by a variety of mutations in the thiazide-sensitive Na-Cl cotransporter.

Aged↗
PubMed1997

Detection of proliferating cell nuclear antigen (PCNA) in peripheral blood mononuclear cells and sera of patients with malignant lymphoma.

Proliferating cell nuclear antigen (PCNA) was detected in the peripheral blood mononuclear cells (PBMC) of patients with malignant lymphoma (ML). Twenty-one of 27 patients with ML had PCNA expressing PBMC (5.25+/-4.75% cells), which tended to increase in the advanced clinical stage of ML. PCNA in PBMC extracts was detected in 11 of 16 patients (54.5+/-41.9 ng/ml). The percentage of PCNA-positive cells correlated significantly with the concentration of PCNA in PBMC extracts (P < 0.005). Serum PCNA was detected in 6 of 16 patients (160.1+/-141.1 ng/ml), but did not correlate with the number of PCNA-positive cells. In some cases, the concentration of serum PCNA increased after chemotherapy while the percent PCNA-positive cells decreased. Our finding indicate that detection of PCNA in PBMC appears to help monitoring the extent of disease in ML and the serum PCNA level may be used in therapeutic studies of lymphoma patients.

Biomarkers, Tumor↗
PubMed1997

Impaired healing of gastric lesions in streptozotocin-induced diabetic rats: effect of basic fibroblast growth factor.

We examined the influence of diabetes on the healing of HCI-induced gastric lesions and the healing promoting effect of basic fibroblast growth factor (bFGF) on these lesions under diabetic conditions induced in rats by streptozotocin (70 mg/kg, i.p.). The experiments were performed using 2-wk streptozocin-diabetic rats with blood glucose levels of >300 mg/dl. After 18 hr fasting, these animals were given 1 ml of 0.6 N HCl by gavage, and 1 hr later they were fed normally before being killed on various days after HCI treatment. Recombinant human basic fibroblast growth factor (acid resistant recombinant human basic fibroblast growth factor mutein CS-23: 10 to 1000 ng/kg x 2, p.o.) or insulin (4 U/rat x 1, s.c.) was given 5 days after HCl treatment. Gastric lesions induced by HCI healed to quiescent state within 5 days both macro- and microscopically. Diabetic conditions did not affect the development of HCI-induced gastric lesions but significantly delayed the healing of these lesions. Daily administration of insulin returned high blood glucose levels to within normal ranges (120-140 mg/dl) and significantly antagonized the delayed healing of these lesions. The delayed healing in diabetic rats was also significantly promoted by recombinant human basic fibroblast growth factor (>300 ng/kg x 2) without any effect on blood glucose level. In normal rats, the mucosal levels of bFGF increased significantly in response to gastric injury at 3 days after HCI treatment. The mucosal bFGF levels in streptozotocin-diabetic rats were significantly lower under basal conditions before HCI treatment and did not increase after injury, yet such dysregulation of bFGF production was partially restored by insulin treatment. rhbFGF even at 1000 ng/kg had no effect on gastric acid secretion in either normal or streptozotocin-diabetic rats. These results suggest that diabetic conditions have deleterious influences on the healing of acute gastric lesions in both an insulin- and bFGF-sensitive manner, and that the administration of exogenous bFGF antagonizes the delayed healing of gastric lesions observed in diabetic animals.

Animals↗
PubMed1997

[Difference of blood cell counts with reference blood cell counters in different makers: Part II].

This is the second report of evaluation on the difference of blood cell counting among different automated blood cell counters in Japan. We tested reference blood cell counters of 6 different companies: Coulter, Sysmex, Bayer-Sankyo, Nihon Kohden, Horiba and Dainabot. Forty ml of whole blood were taken from 3 healthy persons and EDTA-2K anticoagulated blood samples (Sample 1, 2 and 3) were sent to each company to determine blood cell counts with a reference automated counter. As a result, the following items showed more than 10% difference among makers: RBC between Dainabot and Horiba in Sample 3, hematocrit values between Coulter and Dainabot in Sample 2, WBC between Nihon Kohden and each of three makers (Sysmex, Horiba and Dainabot) in all 3 samples and that between Bayer-Sankyo and each of two makers (Sysmex and Horiba) in Sample 3 and platelet count between Dainabot and each of 3 makers (Bayer-Sankyo, Nihon Kohden and Horiba) in all 3 samples. The following items showed difference between 5 and 10%: MCV between Coulter and each of two makers (Bayer-Sankyo and Horiba), WBC between each of two makers (Coulter and Nihon Kohden) and each of other 4 makers, and platelet count between each of two makers (Nihon Kohden and Horiba) and each of 3 makers (Coulter, Sysmex and Bayer-Sankyo). Recently Japanese Committee for Clinical Laboratory Standards proposed minimum clinical allowance of blood cell count as follows: hemoglobin 3%, RBC 4%, MCV 4%, WBC 7% and platelet count 10%. It is suggested that all of the items showing the difference more than above allowance among makers should be improved for clinical use to have good external quality control in blood cell counting by automated instruments.

Blood Cell Count↗
PubMed1997

Human endogenous retroviruses: expression in various organs in vivo and its regulation in vitro.

To evaluate the role of human endogenous retroviruses in vivo, we examined their expressions in various organs from autopsy cases by Northern blot and RT-PCR. ERV3 (HERV-R) mRNA was expressed in many organs, and the level of expression in individuals and organs considerably differed. However, expression in the adrenal gland showed consistently high levels in every individual. lambda 4-1 (HERV-E) mRNA was expressed less compared with that of ERV3, and could not be detected in the adrenal gland by Northern blot, although the expression of lambda 4-1 generally correlated with that of ERV-3 in placentas. We also examined the effect of cytokines on the transcriptional regulation of ERV3 in vitro. Although the level of ERV3 expression in cultured synovial cells did not change after IL-1 beta treatment, the level in cultured proximal tubular epithelial cells was upregulated. The evidence suggests that distinct regulatory pathways may exist for the expression of human endogenous retroviruses in different cell types.

Adrenal Glands↗
PubMed1997

[A case of transient cortical blindness due to reversible ischemic neurological deficit (RIND) after caesarean section under lumbar anesthesia].

We report a case of 31-year-old woman with pregnant toxicosis, who developed transient blindness after caesarean section under lumbar anesthesia. The patient was hypoxic due to atelectasis when she developed blindness, but she had no ophthalmologic abnormalities. MRI depicted abnormal high intensity areas (HIA) with T 2-weighted images (T 2 WI) in the occipital lobes and the basal ganglia. CT could not detect any of these MRI findings. The patient regained her vision four days after the onset. The HIA disappeared in a follow up MRI (T 2 WI) two weeks after the onset. The patient was diagnosed as cortical blindness due to RIND. Although most of the transient cortical blindness are accompanied with pregnant toxicosis with hypertension, there are some cases without pregnant toxicosis. We stress the importance of maintaining the blood pressure within the normal range in patients with hypertension who undergo surgery under spinal anesthesia.

Adult↗