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M Shimizu

Publications and source records attributed to M Shimizu.

At least 19 recordsLinked to original sources

Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning.

Remote ischemic preconditioning reduces myocardial infarction (MI) in animal models. We tested the hypothesis that the systemic protection thus induced is effective when ischemic preconditioning is administered during ischemia (PerC) and before reperfusion and examined the role of the K(+)-dependent ATP (K(ATP)) channel. Twenty 20-kg pigs were randomized (10 in each group) to 40 min of left anterior descending coronary artery occlusion with 120 min of reperfusion. PerC consisted of four 5-min cycles of lower limb ischemia by tourniquet during left anterior descending coronary artery occlusion. Left ventricular (LV) function was assessed by a conductance catheter and extent of infarction by tetrazolium staining. The extent of MI was significantly reduced by PerC (60.4 +/- 14.3 vs. 38.3 +/- 15.4%, P = 0.004) and associated with improved functional indexes. The increase in the time constant of diastolic relaxation was significantly attenuated by PerC compared with control in ischemia and reperfusion (P = 0.01 and 0.04, respectively). At 120 min of reperfusion, preload-recruitable stroke work declined 38 +/- 6% and 3 +/- 5% in control and PerC, respectively (P = 0.001). The force-frequency relation was significantly depressed at 120 min of reperfusion in both groups, but optimal heart rate was significantly lower in the control group (P = 0.04). There were fewer malignant arrhythmias with PerC during reperfusion (P = 0.02). These protective effects of PerC were abolished by glibenclamide. Intermittent limb ischemia during myocardial ischemia reduces MI, preserves global systolic and diastolic function, and protects against arrhythmia during the reperfusion phase through a K(ATP) channel-dependent mechanism. Understanding this process may have important therapeutic implications for a range of ischemia-reperfusion syndromes.

Adenosine Triphosphate↗

The role of muscle grafts in temporomandibular joint ankylosis: short-term experimental study in sheep.

The temporalis muscle flap can be used as an inter-positional graft placed into a gap arthroplasty site in temporomandibular joint (TMJ) ankylosis. The purpose of this study was to investigate the role of the muscle graft in sheep. Five pure-bred adult Merino sheep were used and ankylosis was induced in all right TMJs. At 3 months, the ankylosis was released by gap arthroplasty and reconstructed with a masseter muscle graft, because the temporalis muscle is short and poorly vasculized in sheep. The sheep were killed at 3 months after muscle grafting. The maximal mouth opening was recorded before and after operation and at death. The joints were examined radiologically and histologically. In 4 sheep mouth opening remained at the pre-operative level. A clear radiolucent space remained between the smooth temporal and ramus stumps. Histologically, the muscle graft remained vital but with some fibrous tissue formation between the bone ends. One sheep developed an infection at the operative site following the muscle graft; this partly resolved with antibiotics, but the TMJ developed a fibrous reankylosis that was demonstrated clinically, radiologically and histologically. These results indicate that an uncomplicated temporalis muscle graft reconstruction with gap arthroplasty is a successful and stable procedure in human TMJ ankylosis.

Animals↗

Evaluating stream water quality through land use analysis in two grassland catchments: impact of wetlands on stream nitrogen concentration.

We evaluated the impacts of natural wetlands and various land uses on stream nitrogen concentration in two grassland-dominated catchments in eastern Hokkaido, Japan. Analyzing land use types in drainage basins, measuring denitrification potential of its soil, and water sampling in all seasons of 2003 were performed. Results showed a highly significant positive correlation between the concentration of stream NO3-N and the proportion of upland area in drainage basins in both catchments. The regression slope, which we assumed to reflect the impact on water quality, was 24% lower for the Akkeshi catchment (0.012 +/- 0.001) than for the Shibetsu catchment (0.016 +/- 0.001). In the Akkeshi catchment, there was a significant negative correlation between the proportion of wetlands in the drainage basins and stream NO3-N concentration. Stream dissolved organic nitrogen (DON) and carbon (DOC) concentrations were significantly higher in the Akkeshi catchment. Upland and urban land uses were strongly linked to increases in in-stream N concentrations in both catchments, whereas wetlands and forests tended to mitigate water quality degradation. The denitrification potential of the soils was highest in wetlands, medium in riparian forests, and lowest in grasslands; and was significant in wetlands and riparian forests in the Akkeshi catchment. The solubility of soil organic carbon (SOC) and soil moisture tended to determine the denitrification potential. These results indicate that the water environment within the catchments, which influences denitrification potential and soil organic matter content, could have caused the difference in stream water quality between the two catchments.

Agriculture↗

L-3,4-dihydroxyphenylalanine-induced c-Fos expression in the CNS under inhibition of central aromatic L-amino acid decarboxylase.

L-3,4-dihydroxyphenylalanine (DOPA) is a neurotransmitter candidate. To map the DOPAergic system functionally, DOPA-induced c-Fos expression was detected under inhibition of central aromatic L-amino acid decarboxylase (AADC). In rats treated with a central AADC inhibitor, DOPA significantly increased the number of c-Fos-positive nuclei in the paraventricular nuclei (PVN) and the nucleus tractus solitarii (NTS), and showed a tendency to increase in the supraoptic nuclei (SON), but not in the striatum. On the other hand, DOPA with a peripheral AADC inhibitor elevated the level of c-Fos-positive nuclei in the four regions, suggesting that DOPA itself induces c-Fos expression in the SON, PVN and NTS. In rats treated with 6-hydroxydopamine (6-OHDA) to lesion the nigrostriatal dopamine (DA) pathway, DOPA significantly induced c-Fos expression in the four regions under the inhibition of peripheral AADC. However, under the inhibition of central AADC, DOPA did not significantly increase the number of c-Fos-positive nuclei in the four regions, suggesting that DOPA at least in part induces c-Fos expression through its conversion to DA. It was likely that the 6-OHDA lesion enhanced the response to DA, but attenuated that to DOPA itself. In conclusion, we proposed that the SON, PVN and NTS include target sites for DOPA itself.

Animals↗

Intercellular adhesion molecule-1 mediates the inhibitory effects of hyaluronan on interleukin-1beta-induced matrix metalloproteinase production in rheumatoid synovial fibroblasts via down-regulation of NF-kappaB and p38.

OBJECTIVE: In rheumatoid arthritis (RA), it is well known that rheumatoid synovial fibroblasts (RSF) produce matrix metalloproteinases (MMPs) when stimulated with proinflammatory cytokines such as interleukin-1beta (IL-1beta), which causes joint destruction. We have previously shown that hyaluronan (HA) inhibits IL-1beta actions in RSF via CD44, the principal HA receptor. However, CD44 mediates HA effects only partially, and intracellular events after the HA binding to its receptors remain unclear. We investigated the role of intercellular adhesion molecule-1 (ICAM-1), another cell surface receptor for HA, and the intracellular signalling pathways in the actions of HA. METHODS: RSF were isolated from rheumatoid synovial tissues by enzymatic digestion and cultured in monolayers. The confluent cells were incubated for 48 h with IL-1beta, IL-1beta in the presence of HA, or IL-1beta in the presence of HA with pretreatment with anti-ICAM-1 antibody. Secretion of MMP-1 and MMP-3 was analysed by immunoblotting and immunofluorescence cytochemistry. Immunofluorescence cytochemistry was also performed to evaluate binding of HA to ICAM-1. The phosphorylation of nuclear factor (NF)-kappaB and mitogen-activated protein kinases (MAPKs) was analysed by immunoblotting. RESULTS: Production of MMP-1 and MMP-3 by RSF was stimulated by IL-1beta. HA at > or =2 mg/ml significantly inhibited MMP production induced by IL-1beta in a dose-dependent manner. Moreover, pretreatment with anti-ICAM-1 antibody at 50 mug/ml significantly blocked the effects of HA on the actions of IL-1beta on RSF, as shown by immunoblotting and immunofluorescence cytochemistry. Another immunofluorescence cytochemistry study demonstrated that HA bound RSF via ICAM-1. Inhibition studies revealed the requirement of NF-kappaB, p38 and c-jun NH2-terminal kinase (JNK) for IL-1beta-induced MMP production. IL-1beta activated all three pathways, whereas HA down-regulated their phosphorylation. Pretreatment with anti-ICAM-1 antibody reversed the inhibitory effects of HA on the activation of NF-kappaB and p38 without affecting JNK. CONCLUSION: HA suppresses IL-1beta-enhanced MMP-1 and MMP-3 synthesis in RSF via ICAM-1 through down-regulation of NF-kappaB and p38. Intra-articular injection of HA of high molecular weight may work through such a mechanism in RA joints.

Arthritis, Rheumatoid↗

Inter-individual variation of cytochrome P4502J2 expression and catalytic activities in liver microsomes from Japanese and Caucasian populations.

The aim of this study was to investigate the inter-individual variations in cytochrome P4502J2 (CYP2J2) and its typical drug oxidation activities in human liver microsomes in both Japanese and Caucasian populations. CYP2J2 contents were determined immunochemically in liver microsomes from 20 Japanese and 29 Caucasian samples using recombinant CYP2J2 commercially available as a standard. Ebastine hydroxylation and astemizole O-demethylation activities were compared. The CYP2J2 genotype was determined by direct sequencing of liver genomic DNA. The mean expression levels of CYP2J2 determined immunochemically in liver microsomes from Japanese and Caucasian samples were 2.0 +/- 1.5 and 1.2 +/- 2.1 pmol CYP2J2 mg-1 protein (mean +/- standard deviation), respectively, accounting for 1.8 +/- 1.1% and 0.52 +/- 0.65% of the total hepatic P450 content (0.15 +/- 0.19 and 0.27 +/- 0.14 nmol P450 mg-1 protein, respectively). The individual variation of the two marker drug oxidation activities could not be fully accounted for by the CYP2J2 contents or currently known CYP2J2 genotypes. The amounts of CYP2J2 in liver microsomes with the CYP2J2*7 allele (-76G>T) were decreased to 39% compared with those of liver microsomes from other individuals. The results indicate that CYP2J2 accounts for approximately 1-2% of total P450 in human liver microsomes. The information about large inter-individual variation of the CYP2J2 suggests that this enzyme plays a significant role in the metabolism of xenobiotics and may be useful in in-silico simulations of drug disposition.

Adolescent↗

Surgical management of a double-chambered right ventricle and chylothorax in a Labrador retriever.

A 22-month-old, male Labrador retriever was presented with anorexia, dyspnoea, and fainting. The dog was diagnosed with a double-chambered right ventricle and tricuspid valve dysplasia using echocardiography and cardiac catheterisation. A marked bilateral pleural effusion was also present and chemical analysis of the fluid confirmed the diagnosis of chylothorax. Using echocardiography, a pressure gradient of 87.1 mmHg was found between the proximal and distal chambers of the double-chambered right ventricle. Initiation of cardiopulmonary bypass allowed the anomalous muscle bundle that divided the right ventricle into two chambers to be resected via a right ventriculotomy. The fainting completely resolved postoperatively, and this treatment seemed quite effective in the reduction of pressure overload ascribable to ejection disturbance. Because the tricuspid dysplasia was not corrected in the first operation, the postoperative chyle effusion was reduced but did not cease. A combination of thoracic duct ligation and passive pleuroperitoneal shunting was effective in the resolution of the chyle effusion.

Animals↗

Surgical correction of ventricular septal defect with aortic regurgitation in a dog.

An 8-month-old entire Miniature Dachshund, weighing 4.2 kg, was presented for examination following delvelopment of a cough. Ventricular septal defect had been diagnosed tentatively in its infancy on the basis of a cardiac murmur detected by auscultation and echocardiography. Echocardiography using a B mode right parasternal long-axis view showed a defect at the atrioventricular junction and a thickened cusp of the aortic valve prolapsing into the defect. Colour-flow Doppler showed shunt blood flow across the defect at the level of the atrioventricular junction, from left to right. The sinus of Valsalva was dilated, with turbulent blood flow. Aortic regurgitation was also observed. Cardiac catheterisation studies confirmed the diagnosis of a supracristal ventricular septal defect with aortic regurgitation. Despite medication with digoxin, enalapril and aminophylin, started from the first admission, left ventricular internal dimensions gradually increased, and fractional shortening of the left ventricle gradually decreased. Surgery, with the aid of extracorporeal circulation, to close the ventricular septal defect, was performed 1 year after the initial examination. The aortic valve was left untreated. Postoperatively, the systolic murmur disappeared. Shunt flow from the left to the right ventricle was no longer observed on echocardiography, however there was still a small amount of aortic regurgitation during diastole visualised with colour-flow Doppler echocardiography. The prolapse of the cusp of the aortic valve on B-mode echocardiography was no longer observed and thickening of the cusp had not progressed. Left ventricular function measurement using M mode echocardiography showed a reduced left ventricular volume overload with reduced left ventricular internal dimensions and increased fractional shortening. The cough was relieved and no follow-up medication was scheduled. Early surgical closure of the ventricular septal defect improved the patient's condition and controlled prolapse and thickening of the aortic valve.

Animals↗

CT analysis of the Stafne's bone defects of the mandible.

OBJECTIVE: To investigate the aetiology of Stafne's bone defects by analysing the CT findings of two types of defects, which appeared differently on panoramic radiographs. METHODS: 32 lesions with suspicion of the Stafne's bone defect on a panoramic radiograph were categorised into two groups: typical "Stafne type", which showed the connection to the base of the mandible, and non-typical "Cyst type", which showed no connection. Age, sex, the existence of hypertension and the following CT findings: location, size and inner content of the defect, existence of expansion of the buccal cortical bone, and location of submandibular glands, were analysed. RESULTS: There were 14 "Stafne type" and 17 "Cyst type" on the panoramic radiographs. One lesion in the "Cyst type" was a true cystic lesion and was excluded from further review. The "Stafne type" was seen primarily in the posterior and inferior locations, while the "Cyst type" was seen in the anterior and superior locations on the CT. The size of the defect was significantly larger in the "Stafne type". Buccal cortical expansion was observed only in three lesions in the "Stafne type". While the "Cyst type" contained mainly fatty tissue, the "Stafne type" contained other soft tissues. Though the submandibular glands on the defect side were located anteriorly in both types compared with those on the contralateral side and on the control patients, they spread mainly outwards in the "Stafne type". CONCLUSION: The Stafne's bone defects are thought to be caused by the dislocated submandibular gland. The differences between the two types might occur as a result of a different location of the submandibular gland.

Adipose Tissue↗

Metabolic hormones regulate insulin-like growth factor binding protein-1 mRNA levels in primary cultured salmon hepatocytes; lack of inhibition by insulin.

IGF-binding proteins (IGFBPs) modulate the effects of the IGFs, major stimulators of vertebrate growth and development. In mammals, IGFBP-1 inhibits the actions of IGF-I. Rapid increases in circulating IGFBP-1 occur during catabolic states. Insulin and glucocorticoids are the primary regulators of circulating IGFBP-1 in mammals. Insulin inhibits and glucocorticoids stimulate hepatocyte IGFBP-1 gene expression and production. A 22 kDa IGFBP in salmon blood also increases during catabolic states and has recently been identified as an IGFBP-1 homolog. We examined the hormonal regulation of salmon IGFBP-1 mRNA levels and protein secretion in primary cultured salmon hepatocytes. The glucocorticoid agonist dexamethasone progressively increased hepatocyte IGFBP-1 mRNA levels (eightfold) and medium IGFBP-1 immunoreactivity over concentrations comparable with stressed circulating cortisol levels (10(-9) -10(-6) M). GH progressively reduced IGFBP-1 mRNA levels (0.3-fold) and medium IGFBP-1 immunoreactivity over physiological concentrations (5 x 10(-11)-5 x 10(-9) M). Unexpectedly, insulin slightly increased hepatocyte IGFBP-1 mRNA (1.4-fold) and did not change medium IGFBP-1 immunoreactivity over physiological concentrations and above (10(-9) -10(-6) M). Triiodothyronine had no effect on hepatocyte IGFBP-1 mRNA, whereas glucagon increased IGFBP-1 mRNA (2.2-fold) at supraphysiological concentrations (10(-6) M). This study suggests that the major inhibitory role of insulin in the regulation of liver IGFBP-1 production in mammals is not found in salmon. However, regulation of salmon liver IGFBP-1 production by other metabolic hormones is similar to what is found in mammals.

Animals↗

[Mediastinal lymph node metastasis of thyroid cancer occurring 15 years after the initial operation; report of a case].

A 71-year-old woman was found to have an abnormal shadow on a chest X-ray. Fifteen years earlier she had undergone a subtotal thyroidectomy for thyroid cancer without any lymph node metastasis. Chest computed tomography (CT) revealed a mediastinal tumor with full of blood stream. Since the positron emission tomography (PET) disclosed an increased uptake of fluoro-2-deoxy-D-glucose (FDG) in the tumor, a malignant lymphatic tumor was therefore suspected. An immunohistological examination of biopsy specimens taken by thoracoscopic procedure demonstrated tumor to be lymph node metastasis of the previous thyroid cancer. After a tumor resection by means of a thoracotomy and total thyroidectomy, the patient was scheduled to receive radioiodine therapy. The previously reported cases are also herein reviewed.

Aged↗

The effect of hydroxyethylstarch infusion on bupivacaine pharmacokinetics in rats.

BACKGROUND: Bupivacaine is the agent most often used for labor analgesia. However, the risk of accidental intravascular injection of this drug and consequent acute systemic toxicity is ever-present. Although hydroxyethylstarch (HES) is preferred over crystalloid for prevention of hypotension during regional anesthesia, the pharmacokinetics of bupivacaine during fluid preloading has not been studied. METHODS: Twenty-four awake Sprague-Dawley rats were randomly allocated to receive the continuous intravenous infusion of HES 70K, 200K or 400K, or normal saline (NS). After 1 hour of prehydration all animals received bupivacaine, 1mg kg(-1), bolus, followed by a continuous infusion, 0.4mg kg(-1) min(-1) for 15 minutes. After the completion of bupivacaine infusion serial arterial blood samples to determine the plasma bupivacaine concentration were obtained. The plasma concentration-time profile of bupivacaine was fitted to a two-compartment open model, and the estimated intercepts and slopes were used for calculation of standard pharmacokinetic parameters. RESULTS: The mean peak bupivacaine concentration during HES 400K infusion was significantly lower than during NS infusion (1488 +/- 302 ng ml(-1) vs 2388 +/- 582 ng ml(-1)). Mean volume of distribution in each of the three HES groups was greater than in NS group. Mean area under curves (AUC) during HES 200K and HES 400K infusions were significantly lower than during NS infusion (32534 +/- 4180 and 29619 +/- 4431 min ng ml(-1), respectively, vs 39802 +/- 6268 min ng ml(-1)). Mean total clearance of bupivacaine during HES 200K and HES 400K infusions was significantly higher than during NS infusion (115 +/- 14 and 132 +/- 15 ml min(-1) kg(-1), respectively, vs 92 +/- 14 ml min(-1) kg(-1)). CONCLUSION: Our results suggest that the increased volume of distribution during HES infusion could be counterbalanced by the increased total clearance, resulting in unchanged half-life or elimination rate constant of bupivacaine.

Anesthetics, Local↗

Immunohistochemical characteristics of developing mandibular angle in fetal mice.

Mouse mandibular angle development started as a coagulation of mesemchymal cells on the 15(th) fetal day. On the 16(th )fetal day, cells of the central portion of the cell coagulation showed metachromasia to toluidine blue, and type 2 collagen positive chondrocytes were immunohistochemically detected. After the 17(th) fetal day, cartilaginous osteogenesis occurred with invasion of capillaries. At the same stage, membranous (perichondral) ossification occurred in the periphery of the chondrocyte mass. These proliferating chondrocytes showed positive reactions to type 2 collagen, type 1 collagen and osteopontin. These results suggest that the characteristics of mandibular angular cartilage are slightly different from those of normal physiological articular cartilage.

Animals↗

PRKAR1A gene mutation in patients with cardiac myxoma.

BACKGROUND: PRKAR1A gene encodes the type 1A regulatory subunit of protein kinase A. The mutation of this gene causes Carney complex which is an autosomal dominant multiple neoplasia syndrome characterized by spotty pigmentations, endocrine overactivity and cardiac myxoma. We hypothesized that cardiac myxoma may be associated with PRKAR1A gene mutation and determined whether mutation in the PRKAR1A gene is the cause of familial and sporadic cardiac myxoma. METHODS: We studied seven patients (three males and four females) with cardiac myxoma. Two of them had familial cardiac myxoma complicated with Carney complex. The other five patients were characterized as sporadic cardiac myxomas. We analyzed the PRKAR1A gene of all patients by the polymerase chain reaction (PCR)-single-strand conformation method, followed with direct sequence analysis. RESULTS: We identified a novel mutation (494delTG) in exon 4A of the PRKAR1A gene in the patients with Carney complex. A 16-year-old proband had a left atrial myxoma, pituitary adenoma and skin pigmentation. His father also had left atrial myxoma and skin pigmentation. In contrast, no mutations in the PRKAR1A gene were identified in the other five patients with sporadic cardiac myxomas. CONCLUSIONS: These results suggest that mutation of the PRKAR1A gene may be associated with familial cardiac myxoma in Carney complex but may not be associated with sporadic cardiac myxoma.

Adolescent↗

Genetic variation and geographic distribution of porcine reproductive and respiratory syndrome virus in Japan.

Porcine reproductive and respiratory syndrome virus (PRRSV) has two genotypes, the North American-type (NA-type) and the European-type (EU-type), and each genotype is also genetically diverged. We sequenced the ORF5 gene of 30 PRRSVs isolated from 23 prefectures of Japan during 1992 and 1993 and during 2000 and 2001. All of the isolates were of the NA-type. Phylogenetic analysis of the overall NA-type viruses isolated from around the world identified five major genetic clusters. The 1992-1993 Japanese samples belonged to only two genetic clusters, while the 2000-2001 samples included more diverged ORF5 genomes. One genetic cluster, which included 63% (20/32) of Japanese isolates, one Taiwanese isolate and one Chinese isolate, was mainly found in the eastern part of Japan. Another genetic cluster, which was found in various areas around the world, was distributed in the western part of Japan.

Animals↗

Influence of sodium benzoate on the metabolism of o-xylene in the rat.

The main metabolites of o-xylene in urine are o-methylhippuric acid, o-toluic acid, o-toluic acid glucuronide, 3,4-dimethylphenol, 3,4-dimethylphenol conjugates and o-xylylmercapturic acid. The urinary excretion of o-toluic acid, o-toluic acid conjugates and o-xylene were increased by the prior administration of sodium benzoate. Conversely, the amounts of o-methylhippuric acid, 3,4-dimethylphenol conjugates and o-xylylmercapturic acid decreased by sodium benzoate pretreatment. In addition, the urinary excretion of o-methylhippuric acid was delayed by the pretreatment. The percentages of urinary excretion of the o-xylene metabolites were substantially changed by the pretreatment with sodium benzoate. These results therefore highlight a potential interaction of an air pollutant with a food additive, an interaction that remains to be established in man.

Animals↗

Pathology of experimental disuse muscular atrophy in rats.

The relationship between structural changes and hyaluronic acid (HA) content in muscular atrophy is unknown. The objective of our study was to conduct multifaceted evaluations of the change in muscle extensibility in muscular atrophy, in terms of morphological aspects as well as from a biochemical viewpoint, including changes in intercellular substances. Using a muscular atrophy model of the soleus muscle in the cast-fixed limbs of Wistar rats, we examined changes in HA accompanying muscular atrophy. Compared with controls, the cast-fixed limbs showed histological evidence of muscular atrophy and electron microscopy indicated destruction of the fasciae. Measurement of the HA level in muscle tissue from cast-fixed rats indicated a reduction in concentration per unit of weight. In contrast, serum HA concentrations increased in the cast-fixed group compared with the control group, suggesting that HA present in the fasciae was released into the blood stream during muscular atrophy.

Animals↗