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M Hori

Publications and source records attributed to M Hori.

At least 181 records · Page 10Linked to original sources
PubMed2000

The involvement of cytokines in the second window of ischaemic preconditioning.

We utilized a rat model of myocardial infarction to investigate whether manganese superoxide dismutase (Mn-SOD), an intrinsic radical scavenger, and tumour necrosis factor- alpha (TNF-alpha) and/or interleukin-1beta (IL-1beta) are involved in the late phase of ischaemic preconditioning (IP). IP was induced in anaesthetized rats by four 3-min left coronary artery (LCA) occlusions, each separated by 10 min of reperfusion. Twenty-four hours after the repetitive brief ischaemia, the LCA was occluded for 20 min followed by reperfusion for 48 h. IP reduced the infarct size by approximately 46% as determined after 48 h of reperfusion. Antisense oligodeoxynucleotides to Mn-SOD inhibited the increases in Mn-SOD content and activity, and abolished the expected decrease in myocardial infarct size. Sense or scrambled oligodeoxynucleotides did not abolish either Mn-SOD induction or tolerance to ischaemia/reperfusion. The simultaneous administration of the antibodies to TNF-alpha (0.5 ml) and IL-1beta (0.5 mg) prior to IP abolished the cardioprotection and the increase in Mn-SOD activity induced by IP. We conclude that the induction and activation of Mn-SOD, mediated by TNF-alpha and IL-1beta after IP, plays an important role in the acquisition of late-phase cardioprotection against ischaemia/reperfusion injury in rats.

Analysis of Variance↗
PubMed2000

Platelet-derived growth factor causes endothelium-independent relaxation of rabbit mesenteric artery via the release of a prostanoid.

Recent evidence has indicated that the mitogen platelet-derived growth factor (PDGF) can act acutely to regulate arterial tone. In this study we demonstrate that the BB isoform of PDGF (PDGF-BB) can cause endothelium-independent relaxation of rabbit isolated mesenteric arteries. In endothelium-denuded arteries, PDGF-BB (40 pM - 8.0 nM) caused concentration-dependent relaxation of noradrenaline-induced tone. The relaxation to PDGF-BB was abolished by a cyclo-oxygenase inhibitor, indomethacin (10 microM) and by the PDGF receptor-associated tyrosine kinase inhibitor, tyrphostin AG1295 (50 microM), but not by N:(G)-monomethyl-L-arginine (L-NMMA, 200 microM), an inhibitor of nitric oxide (NO) synthase. PDGF-BB (4.0 nM) significantly increased the release of prostacyclin (PGI(2)) in endothelium-denuded arteries. Exogenously applied iloprost (1 microM), a stable analogue of PGI(2), relaxed the endothelium-denuded artery. PDGF-BB (4.0 nM) significantly increased the cyclic AMP content. In the absence of Ca(2+), PDGF-BB (4.0 nM) failed to relax the artery, and the release of PGI(2) was almost completely suppressed. In addition, the release of PGI(2) by PDGF-BB (4.0 nM) was significantly reduced in the presence of endothelium. The effect of endothelium was eliminated by L-NMMA (200 microM) and PGI(2) release increased. These data indicate that in rabbit mesenteric arteries, PDGF-BB can evoke endothelium-independent relaxation by stimulating the synthesis of PGI(2). The PDGF-BB-induced prostaglandin synthesis is dependent on both Ca(2+) and tyrosine phosphorylation of the PDGF receptor, and is attenuated by endothelium-derived NO.

Animals↗
PubMed2000

A novel strategy for cancer therapy by mutated mammalian degenerin gene transfer.

Mammalian degenerin (MDEG) is a member of the amiloride-sensitive sodium ion channel family, and its site-directed active mutant (MDEG-G430F) induces massive Na+ influx into cells, leading to cell ballooning and cell bursting. We attempted a novel therapeutic approach for gastric cancers by transferring MDEG-G430F into cancer cells using tumor-specific promoters. In carcinoembryonic antigen (CEA)-producing gastric cancer cells, the level of cell death observed when MDEG-G430F was used with a CEA promoter was similar to that observed when using a potent nonspecific promoter such as the cytomegalovirus promoter. In an in vivo study, fusogenic liposome complexes containing MDEG-G430F driven by the CEA promoter were injected intraperitoneally into CEA-producing gastric cancer cells in a mouse peritoneal dissemination model. Although all 15 of the control mice were dead by 50 days postinoculation, 13 of the 15 mice treated with MDEG-G430F survived. These results indicate that transferring MDEG-G430F into cancer tissues using tumor-specific promoters can achieve striking and selective cancer cell death irrespective of the transcriptional efficiency of the promoters used in vivo, and suggest that this approach is a promising new strategy for cancer gene therapy.

Acid Sensing Ion Channels↗
PubMed2000

Evaluation of gut motility in type II diabetes by the radiopaque marker method.

BACKGROUND: The clinical usefulness of the radiopaque marker method for detecting diabetic gastrointestinal motility disturbances, was evaluated by examining 21 type II diabetes subjects who did not have any neuropathic symptoms. METHODS: After administration of a Sitzmark capsule, markers were located using plain abdominal radiographs, and the transit time of the markers through seven areas of digestive tract was calculated by Arhan's methods. The plasma concentration of acetaminophen at 45 min after oral administration was measured to evaluate gastric emptying time. The coefficient of variation of R-R intervals on the electrocardiograms (CV(R-R)) was measured to evaluate parasympathetic autonomic function. RESULTS: In the diabetics, the average (+/- SD) transit time through upper digestive tracts was slightly but not significantly elongated compared with control subjects (14.4 +/- 8.3 vs 9.9 +/- 6.1 h). Significant elongation was observed in transit time through the lower digestive tracts or the whole gut (44.6 +/- 20.9 and 57.9 +/- 22.3 h, respectively) compared with control subjects (23.3 +/- 8.5 and 33.2 +/- 11.0 h). The transit time of the markers from stomach to small intestine was highly correlated (r = 0.693) with plasma concentration of acetaminophen. The transit time through either the whole colon (r = 0.564) or the whole gut (r = 0.630) was highly correlated with CV(R-R). CONCLUSIONS: These findings suggest that the radiopaque marker method is a useful tool for detecting the sections of the digestive tract responsible for gut motility disturbances. In type II diabetics with no neuropathic symptoms, the lower digestive tracts may deteriorate prior to the impairment of upper digestive tracts.

Acetaminophen↗
PubMed2000

Cyclo-oxygenase-2 inhibitors suppress epithelial cell kinetics and delay gastric wound healing in rats.

BACKGROUND AND AIMS: The present study examined the effects of NS-398, a specific cyclo-oxygenase-2 inhibitor, on gastric mucosal cell kinetics and gastric wound healing following acid-induced injury. METHODS: Male Sprague-Dawley rats were fasted for 24 h and then 0.6 mol/L hydrochloric acid (HCl; 1 mL) was administered into the stomach; NS-398 or indomethacin was administered to the animals 10 min after the acid. Levels of constitutive cyclo-oxygenase (COX-1) and mitogen-inducible cyclo-oxygenase (COX-2) in the gastric mucosa were analysed using western blotting and immunohistochemical staining. The grade of the lesion was assessed using planimetry and histological examination, including immunohistochemistry for proliferating cell nuclear antigen (PCNA). RESULTS: Although there was strong expression of COX-1, there was minimal expression of COX-2 in the gastric mucosa. Expression of COX-2 was enhanced mainly in surface epithelial cells and neck cells following HCl administration. Gastric mucosal ulcers and erosions healed within 48 h, during which time the proliferative zone expanded in the control animals. Indomethacin and NS-398 suppressed the expansion of the proliferative zone and delayed the healing of the gastric injury. CONCLUSION: The present study demonstrated that cyclo-oxygenase-2 inhibitors delay gastric wound healing by suppressing expansion of the mucosal proliferative zone. These results provide evidence that cyclo-oxygenase-2 has an important role in gastric mucosal regeneration.

Animals↗
PubMed2000

Tardive dystonia provoked by concomitantly administered risperidone.

Two cases of tardive dystonia are reported. The first case was an 18-year-old schizophrenic woman suffering from parkinsonism and hypotension induced by antipsychotic drugs. Risperidone (4 mg/day) was added to her drug regimen and after increasing the dosage to 6 mg/day, she began to exhibit retrocollis. The second case was a 61-year-old woman who had schizophrenia and tardive dyskinesia. After replacing chlorpromazine (75 mg/day) with risperidone (4 mg/day), she began to exhibit retrocollis. The retrocollis in both cases was considered to be tardive dystonia provoked by risperidone administered concomitantly with other antipsychotics. Risperidone is reported to produce few extrapyramidal symptoms, but these cases suggested that changing from other drugs to risperidone, or rapidly increasing risperidone dosage, may provoke tardive syndrome.

Adolescent↗
PubMed2000

Alternatively spliced MDM2 transcripts in human breast cancer in relation to tumor necrosis and lymph node involvement.

Several short forms of alternatively spliced Murine double minute 2 (MDM2) transcripts have recently been shown to correlate with high-grade malignancy in a number of human tumors. We examined the frequency of splice variants and their correlation with clinicopathological features in 60 cases of human breast cancer. Seven short forms coexpressed with wild-type mRNA were detected by nested RT-PCR. Sequencing of all the MDM2 variants demonstrated mRNA splicing which disrupted not only the conserved p53-binding domain but also, further towards the carboxy-terminus, the conserved nuclear localization sequence and/or the acidic and zinc finger domains. There was no significant correlation between the coexpression of splice variants and tumor size, histologic type or hormone (estrogen and progesterone) receptor status. However, cases with spliced MDM2 transcripts tended to be of a more aggressive type with axillary lymph node involvement and extensive necrosis in the tumors. Although the functional significance of MDM2 variants remains obscure, we anticipate that these variants will be confirmed as a novel prognostic marker in human breast cancer.

Adenocarcinoma↗
PubMed2000

Gene transfer targeting interstitial fibroblasts by the artificial viral envelope-type hemagglutinating virus of Japan liposome method.

BACKGROUND: Tubulointerstitial inflammation and fibrosis are commonly associated with most human glomerular diseases. The degree of tubulointerstitial damage, rather than the glomerular injury, could correlate with the degree of renal functional impairment and accurately predict long-term prognosis. In an effort to understand the pathogenesis of the progressive interstitial fibrosis, we developed a new strategy of gene transfer to the interstitial fibroblasts. METHODS: Either fluorescein isothiocyanate (FITC)-labeled oligodeoxynucleotides (ODNs) or pEBAct-NlacF expression vector was introduced into the kidney of normal rats retrogradely via ureter by using the artificial viral envelope (AVE)-type hemagglutinating virus of Japan (HVJ) liposome method. RESULTS: FITC-labeled ODNs were accumulated diffusely in the nuclei of the interstitial cells in the transfected kidney 10 minutes after transfection, and the interstitial cells were identified as interstitial fibroblasts by immunostaining with ER-TR7. To examine the gene expression in the interstitium, pEBAct-NlacF gene-conjugated HVJ liposome was injected retrogradely through the ureter, and in consequence, nuclear beta-galactosidase activity was continuously observed in interstitial cells at least two weeks after transfection. CONCLUSION: This new strategy of gene transfer to the interstitial fibroblasts is useful for the investigation of the pathophysiology of tubulointerstitial lesion, and furthermore, it may be a promising new therapeutic method for the progression of interstitial fibrosis.

Animals↗
PubMed2000

Gene expression profiles of the collecting duct in the mouse renal inner medulla.

UNLABELLED: Gene expression profiles of the collecting duct in the mouse renal inner medulla. BACKGROUND: Gene expression profiles, constructed from 1000 to 2000 cloned cDNA sequences, depict their relative abundance of expression in a tissue. Establishing such a profile for mouse inner renal medullary collecting ducts (IMCDs), we compared expression patterns with those in other tissues including proximal tubule. METHODS: A nonbiased 3'-end cDNA library was prepared from microdissected mouse IMCDs. Single-pass sequencing of 2000 randomly selected cDNA clones collected short sequences (approximate length, 250 bp) following poly (A), called gene signatures (GS). Identical sequences were considered a single GS. GS occurrence was quantitated to yield a list of expressed genes indicating their abundance. RESULTS: Among 2000 clones, 1613 types of transcripts were found in IMCDs; 155 were identical or homologous to reported genes. The gene most expressed in IMCDs was alphaB-crystallin, a small stress (heat-shock) protein that is also a major structural protein in the ocular lens. According to Northern analysis, renal expression of this mRNA was induced by dehydration, presumably via tissue hypertonicity. However, expression did not change with acute NaCl loading. Also, a new member of the glutathione-S-transferase family was identified by comparing the IMCD expression profile with those of other tissues. CONCLUSION: With our database of genes expressed in mouse IMCDs, we are devising an IMCD-specific microarray to study gene-expression responses to various physiologic alterations.

Amino Acid Sequence↗
PubMed2000

Quantitation of mRNA expression in glomeruli using laser-manipulated microdissection and laser pressure catapulting.

BACKGROUND: Laser-manipulated microdissection (LMM) is a method to cut out a single cell or limited tiny region from a specimen under microscopic observation by a laser beam. Laser pressure catapulting (LPC) is a method to push up and collect samples that were microdissected using a strong laser. METHODS: To induce experimental glomerulonephritis, anti-Thy1.1 monoclonal antibody (OX-7) was injected intravenously into rats. Control and disease model kidneys were obtained. Six-micrometer thick cryostat sections were mounted onto a 1.35 microm thin polyethylene membrane. Ten glomeruli were collected from 6 microm frozen sections of rat kidney by LMM and LPC. Isolated glomeruli were used to quantitate the expression of mRNA by real-time polymerase chain reaction (PCR). RESULTS: Transforming growth factor-beta1 (TGF-beta1) mRNA was not detected in glomeruli isolated by the LMM and the LPC methods on day 0, although G3PDH mRNA was measurable in the same samples. On day 7 after the treatment with OX-7, the ratio of TGF-beta1/G3PDH mRNA was 1.89 +/- 0.96 (N = 6). CONCLUSIONS: We established methods to isolate glomeruli from standard histochemical specimens by LMM and LPC, and to quantify mRNA expression in the targeted glomeruli using real-time PCR. We confirmed the up-regulation of TGF-beta1 mRNA expression in isolated glomeruli from frozen sections of the anti-Thy1.1 glomerulonephritis model.

Animals↗
PubMed2000

Probability of hepatocellular carcinoma of small hepatocellular nodules undetectable by computed tomography during arterial portography.

Recent advances in imaging modalities enable the identification of small hepatocellular nodules. Among the imaging techniques currently used for detecting hepatocellular carcinomas (HCC), computed tomography (CT) during arterial portography (CTAP) is one of the most sensitive techniques available for detecting hemodynamic change. Even so, well-differentiated HCCs that display only limited hemodynamic change, a feature shared with nonmalignant hepatocellular nodules, are not always detectable by CTAP. To improve our ability to distinguish well-differentiated HCCs from nonmalignant hepatocellular nodules, we have attempted to clarify how the characteristics of the nodules are shown by each imaging technique. We studied the imaging and pathological characteristics of 31 nodules (in 22 patients) detected by ultrasonography (US), but not by CTAP. Histological diagnoses were as follows: HCC, 17 of 31 nodules (55%); high-grade dysplastic nodules, 1 of 31 (3%); and nonmalignant nodules, 13 of 31 (42%). Neither digital substraction angiography (DSA) nor CT arteriography (CTA) were able to detect any of the nodules. Detection rates for plain CT were: 5 of 17 (29%) HCC, 1 of 1 (100%) high-grade dysplastic nodules, and 1 of 13 (8%) nonmalignant nodules. Detection rates for T1/T2-weighted magnetic resonance imaging (MRI) were: 4 of 17 (24%) HCC, 1 of 1 (100%) high-grade dysplastic nodules, and 3 of 13 (23%) nonmalignant nodules. Dynamic CT and dynamic MRI provided no additional information. In conclusion, there is some probability that hepatocellular nodules detected by US, but not by CTAP, are HCC. Presently, it is difficult to distinguish between benign nodules and malignant ones with these imaging techniques, and our findings indicate that biopsy may be advisable for nodules detected under these conditions.

Adult↗
PubMed2000

Expression of cyclooxygenase-2 and nitrotyrosine in human gastric mucosa before and after Helicobacter pylori eradication.

To determine whether cure of Helicobacter pylori infection influences the expression of COX-2 and nitrotyrosine in the distal stomach of humans, biopsy specimens were examined immunohistochemically. H. pylori infection was determined using a rapid urease test, culture and histology. Positive staining of COX-2/nitrotyrosine in the epithelium was expressed as the percentage of stained cells to the total epithelial cells. There was a significant increase in COX-2/nitrotyrosine staining in H. pylori -positive subjects compared with H. pylori -negative subjects. Cure of the infection resulted in a significant decrease in both COX-2/nitrotyrosine staining in all patients (52.1+/-12.1% vs 15. 4+/-7.2%, P<0.001; and 57.3+/-13.6% vs 36.1+/-18.0%, P<0.01, respectively). However, immunoreactivity of COX-2/nitrotyrosine was observed in all cases with intestinal metaplasia even after the cure of H. pylori infection.Thus, cure of H. pylori infection may decrease the risk of gastric carcinogenesis due to COX-2 and NO-related compounds in gastric mucosa but not in those patients with intestinal metaplasia.

Adult↗
PubMed2000

High-frame-rate tissue harmonic imaging enhances anatomic M-mode sections of the left ventricle in short-axis view.

BACKGROUND: High-frame-rate echocardiography (HFRE) and tissue harmonic imaging (THI) may improve image quality, thereby enabling anatomic M-mode sections of left ventricular (LV) wall segments to be visualized in various planes in the short-axis view. OBJECTIVES: The goals of this study were to compare image quality between HFRE and conventional-frame-rate echocardiography (CFRE) and between fundamental imaging (FI) and THI, and to obtain anatomic M-mode values of basal short-axis LV segments from healthy subjects for use in the evaluation of abnormal segments in patients with myocardial infarction (MI). METHODS AND RESULTS: The study included 28 healthy subjects and 15 patients with MI who underwent 2-dimensional echocardiography with an ultrasonographic system equipped with THI and anatomic M-mode. Left ventricular image cineloops at the basal short-axis view that were obtained with 3 combinations of imaging techniques (FI + CFRE, FI + HFRE, and THI + HFRE) were digitized and displayed side-by-side in random order for comparison by blinded readers. M-mode sections were done in 3 planes: anteroseptal-posterior, inferoseptal-lateral, and anterior-inferior basal segments. The THI + HFRE combination showed the best image quality with significant reduction in noise artifacts, resulting in a good signal-to-noise ratio and good tractability of all LV segments by anatomic M-mode. In healthy subjects, significant intersegmental differences existed in the diastolic and systolic thicknesses and in the percent systolic thickening of LV segments. In patients with MI, LV systolic thickening was significantly decreased in abnormal segments. No significant differences were noted in ejection fraction and fractional shortening among the 3 anatomic M-mode planes. CONCLUSION: High-frame-rate tissue harmonic imaging improved image quality, thereby allowing reproducible anatomic M-mode measurements in various planes in the short-axis view and providing a convenient objective evaluation of global and regional LV function.

Adult↗
PubMed2000

Myocardial longitudinal motion by tissue velocity imaging in the evaluation of patients with myocardial infarction.

Left ventricular (LV) longitudinal shortening plays an important role in cardiac contraction and is invariably affected by the presence of coronary artery disease. Third-generation tissue velocity imaging (TVI) color-maps cardiac movement by obtaining mean velocities of LV segments from the same set of beats. The goals of this study were to characterize patterns of longitudinal myocardial motion velocity in healthy subjects and to use these patterns to evaluate abnormal segments of patients with myocardial infarction (MI). Included were 20 healthy subjects and 16 patients with MI who underwent a 2-dimensional Doppler echocardiography study. Myocardial velocity profiles were taken at the anulus, basal, mid, and apical segments of the septal and lateral walls in the apical view. Segmental velocity patterns from healthy subjects were compared with abnormal segments in patients with MI. Both lateral and septal walls of healthy subjects showed significant basal-apical myocardial velocity reductions in systolic shortening (Sm) and early and late diastolic lengthening (Em and Am) and a basal-apical increase in the Em/Am ratio. The lateral wall had greater Sm and Em velocities than the septal wall. The Sm and Em velocities and the Em/Am ratio were significantly reduced in the abnormal segments in patients with MI. Latent lateral wall ischemia may have been detected in 5 of 9 patients with septal infarction, showing reduced Sm velocity in apparently normal lateral walls. In conclusion, TVI objectively quantifies directional and incremental changes in myocardial movement that are useful in evaluating global and regional myocardial function, and it may play a role in the detection of early myocardial ischemia.

Adult↗
PubMed2000

FR167653, a cytokine-suppressive agent, reduces myocardial ischemia-reperfusion injury in rats.

FR167653 inhibits the production of inflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) in human monocytes in a dose-dependent manner. We examined the effects of FR167653 on the propagation of myocardial infarction resulting from coronary occlusion-reperfusion and the time course of expression of these cytokines in myocardial tissue in rats. Myocardial infarction was induced by coronary ligation for 20 minutes followed by 2 hours of reperfusion. Although hemodynamic parameters did not differ significantly during coronary occlusion-reperfusion, the size of the infarct was significantly reduced by intravenous administration of FR167653 before occlusion (p < 0.01). mRNA levels of IL-1beta and TNF-alpha assessed by the reverse-transcriptase polymerase chain reaction method were significantly increased during coronary occlusion-reperfusion in the ischemic myocardium. Treatment with FR167653, however, significantly reduced the increased expression of these cytokines. These results indicate that the expression of inflammatory cytokines increases in the ischemic-reperfused myocardium and that the inhibition of the increased expression of cytokines by FR167653 effectively reduces myocardial ischemia-reperfusion injury.

Animals↗
PubMed2000

A clinicopathological study of IgA nephropathy in renal transplant recipients: beneficial effect of angiotensin-converting enzyme inhibitor.

BACKGROUND: Prolonging the survival of transplant kidneys is a major task of modern nephrology. It has recently been shown that deteriorating renal function and substantial graft loss were observed in 55% of renal allograft recipients with recurrent IgA nephropathy (IgAN) at long-term follow-up. To gain a useful insight into the therapeutic approach towards protecting allograft kidneys from deteriorating graft function, we compared the histological characteristics of post-transplant IgAN to primary IgAN and investigated the effects of an ACE inhibitor. METHODS: Twenty-one patients with post-transplant IgAN and 63 patients with primary IgAN were included in the histopathological study. The effectiveness of angiotensin-converting enzyme (ACE) inhibitor treatment in post-transplant IgAN was also studied in 10 patients. RESULTS: The prevalence of glomeruli with adhesions and/or cellular crescents in primary IgAN was significantly greater than in post-transplant IgAN (P<0.05), but the proportion of glomeruli with segmental sclerosis was similar in both groups. The rate of global obsolescence, and the degree of interstitial fibrosis in post-transplant IgAN were significantly greater than in primary IgAN (P<0.05). The degree of glomerular obsolescence and the severity of interstitial fibrosis correlated with the severity of glomerular lesion in primary IgAN, but not in post-transplant IgAN. In primary IgAN, glomerular diameter significantly correlated with the proportions of glomerular obsolescence, but not in post-transplant IgAN, suggesting that allograft kidneys may be in a hyperfiltration state. Both the blood pressure and the urinary protein excretion significantly improved after ACE-inhibitor treatment (P<0.001). CONCLUSION: In post-transplant IgAN, histopathological lesions indicative of acute inflammatory insults were suppressed, and glomerular hypertrophy, which may relate to haemodynamic burden such as hyperfiltration, was prominent. Preliminary study of ACE-inhibitor treatment in 10 patients showed favourable effects. A future long-term follow-up study is required to establish the effectiveness of ACE inhibitors in treatment of post-transplant IgAN.

Adult↗