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M Ohara

Publications and source records attributed to M Ohara.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Current topics in the regulation of prostanoids--4. The feedback regulation by PPAR-gamma].

Recently, it has become known that lipophilic hormones such as steroids and thyroid hormones, or fat-soluble vitamins (vitamins A and D) pass through the cellular membrane and bind to the nuclear receptor superfamily to act as transcription factors. The metabolite of prostaglandin (PG) D2, 15-deoxy-D12,14PGJ2, has been identified as the ligand for peroxisome proliferator-activated receptor gamma (PPAR-gamma), a member of the nuclear receptor superfamily. It forms a transcription factor and is responsible not only for the differentiation of fibroblasts to adipocytes, but also for the regulation of activated macrophages. It is now known that thiazolidinediones and non-steroidal anti-inflammatory drugs classified as cyclooxygenase blockers such as indomethacine and ibuprofen also act as PPAR-gamma agonists and inhibit cytokine production from activated macrophages. PPAR-gamma has become recognized as a new therapeutic target for inflammation control.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

[Efficacy of intra-arterial chemotherapy on life prolongation in patients with hepatic metastasis from colorectal cancer].

The efficacy of intra-arterial chemotherapy for life prolongation was investigated in patients with hepatic metastasis from colorectal cancer who visited our hospital from Jan. 1989-Mar. 1999, but without any other remote metastasis when the presence of their hepatic metastasis was detected. The subjects were assigned to 4 groups; group A (n = 8) was only treated by hepatectomy, group B (n = 27) by intra-arterial chemotherapy combined with hepatectomy, group C (n = 42) with intra-arterial chemotherapy alone, and group D (n = 23) by systemic chemotherapy through intra-venous or oral administration. The survival rates of these groups were determined, and the recurrence risk after hepatectomy was compared between group A and B. Further, the survival rate of the patients treated by intra-arterial chemotherapy was compared between the cases of PD and not-PD (including CR, PR, and NC). The median survival in cases of H1 and H2 was 405 days for group A, 1,018 days for group B and 245 days for group C, showing that group B had a significantly more favorable prognosis than either group A or group C. There were also significant differences in the median survival of H3 cases between group C (422 days) and group D (113 days). One-year cumulative recurrence risks in the residual livers of group A and group B were 79% and 28%, respectively. Thus, significant differences in the recurrence risk were found in the two groups. Meanwhile, the median survival of PD and non-PD cases was 240 and 588 days, respectively. These results suggested that local control by intra-arterial chemotherapy is useful for life prolongation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Upregulation of aquaporin 2 water channel expression in pregnant rats.

Water retention is characteristic of pregnancy but the mechanism(s) of the altered water metabolism has yet to be elucidated. The collecting duct water channel, aquaporin 2 (AQP2), plays a pivotal role in the renal water regulation, and we hypothesized that AQP2 expression could be modified during pregnancy. Sprague-Dawley female rats were studied on days 7 (P7), 14 (P14), and 20 (P20) of pregnancy, and expression of AQP2 in papillae was examined. Nonpregnant (NP) littermates were used as controls. Plasma osmolalities were significantly lower in pregnant rats by day 7 of gestation (P7 283.8+/-1.82, P14 284.3+/-1.64, P < 0.001, P20 282. 4+/-1.32, P < 0.0001, vs. NP 291.8+/-1.06 mosmol/kgH2O). However, plasma vasopressin concentrations in pregnant rats were not significantly different than in nonpregnant rats (NP 1.03+/-0.14, P7 1.11+/-0.21, P14 1.15+/-0.21, P20 1.36+/-0.24 pg/ml, NS). The mRNA of AQP2 was increased early during pregnancy: AQP2/beta actin: P7 196+/-17.9, P14 200+/-6.8, and P20 208+/-15.5%, P < 0.005 vs. NP (100+/-11.1%). AQP2 protein was also increased during pregnancy: AQP2 protein: P7 269+/-10.0, P14 251+/-12.0, P < 0.0001, and P20 250+/-13.6%, P < 0.001 vs. NP (100+/-12.5%). The effect of V2 vasopressin receptor antagonist, OPC-31260, was then investigated. AQP2 mRNA was suppressed significantly by OPC-31260 administration to P14 rats (AQP2/beta actin: P14 with OPC-31260 39.6+/-1.7%, P < 0.001 vs. P14 with vehicle) and was decreased to the same level of expression as NP rats receiving OPC-31260. Similar findings were found with the analysis of AQP2 protein. The decreased plasma osmolality of P14 rats was not modified by OPC-31260. The results of the study indicate that upregulation of AQP2 contributes to the water retention in pregnancy through a V2 receptor-mediated effect. In addition to vasopressin, other factors may be involved in this upregulation.

Actins↗
PubMed1998

Nitric oxide synthase (NOS) inhibition for one week improves renal sodium and water excretion in cirrhotic rats with ascites.

Normalization of the increased vascular nitric oxide (NO) generation with low doses of NG-nitro-L-arginine methyl ester (L-NAME) corrects the hemodynamic abnormalities of cirrhotic rats with ascites. We have undertaken this study to investigate the effect of the normalization of vascular NO production, as estimated by aortic cyclic guanosine monophosphate (cGMP) concentration and endothelial nitric oxide synthase (eNOS) protein expression in the aorta and mesenteric artery, on sodium and water excretion. Rats with carbon tetrachloride-induced cirrhosis and ascites were investigated using balance studies. The cirrhotic rats were separated into two groups, one receiving 0.5 mg/kg per day of L-NAME (CIR-NAME) during 7 d, whereas the other group (CIR) was administrated the same volume of vehicle. Two other groups of rats were used as controls, one group treated with L-NAME and another group receiving the same volume of vehicle. Sodium and water excretion was measured on days 0 and 7. On day 8, blood samples were collected for electrolyte and hormone measurements, and aorta and mesenteric arteries were harvested for cGMP determination and nitric oxide synthase (NOS) immunoblotting. Aortic cGMP and eNOS protein expression in the aorta and mesenteric artery were increased in CIR as compared with CIR-NAME. Both cirrhotic groups had a similar decrease in sodium excretion on day 0 (0.7 versus 0.6 mmol per day, NS) and a positive sodium balance (+0.9 versus +1.2 mmol per day, NS). On day 7, CIR-NAME rats had an increase in sodium excretion as compared with the CIR rats (sodium excretion: 2.4 versus 0.7 mmol per day, P < 0.001) and a negative sodium balance (-0.5 versus +0.8 mmol per day, P < 0.001). The excretion of a water load was also increased after L-NAME administration (from 28+/-5% to 65+/-7, P < 0.05). Plasma renin activity, aldosterone and arginine vasopressin were also significantly decreased in the CIR-NAME, as compared with the CIR rats. The results thus indicate that normalization of aortic cGMP and eNOS protein expression in vascular tissue is associated with increased sodium and water excretion in cirrhotic rats with ascites.

Aldosterone↗
PubMed1998

[Clinical evaluation of Dumon stent for tracheobronchial stenosis due to advanced esophageal carcinoma].

We inserted Dumon stent to 13 patients with tracheobronchial stenosis due to advanced or recurrent esophageal carcinoma. Severe dyspnea was improved in 11 patients except for 2 patients with bilateral recurrent nerve palsy. 3 cases who had radiation therapy or chemotherapy lived over 150 days. We inserted esophageal stent in 4 cases. 2 patients died due to hemoptysis after 156 days and 35 days. We conclude that Dumon stent is one of the useful treatments in order to improve quality of life and prognosis of advanced or recurrent esophageal carcinoma.

Aged↗
PubMed1998

Suppression of carcass weight loss in cachexia in rats bearing Leydig cell tumor by the novel compound NO-1886, a lipoprotein lipase activator.

The Leydig cell tumor has been reported to produce tumor necrosis factor (TNF) and induce cachexia in rats. TNF is thought to reduce lipoprotein lipase (LPL) activity, decrease fat deposits, induce emaciation, and worsen cachexia. Therefore, we thought emaciation might be prevented and thus cachexia improved by increasing LPL activity. We administered NO-1886, a lipoprotein lipase activator, to rats bearing Leydig cell tumor and observed its effect on improving the cachexia induced by the tumor. In Leydig cell tumor-bearing rats, the emaciation progressed after tumor inoculation and the general condition worsened daily. Plasma levels of total protein, albumin, and glucose, which are biological parameters of malnutrition, were found to decrease soon after tumor inoculation in tumor-bearing rats. In contrast, rats given NO-1886 showed less malnutrition than tumor-bearing rats. LPL activity of rat adipose tissue was decreased, the weight of adipose tissue was decreased, carcass weight was reduced, and food consumption was decreased after Leydig cell tumor inoculation. NO-1886 increased adipose tissue LPL activity and suppressed the decrease in the weight of adipose tissue, carcass weight, and food consumption due to cachexia without influencing tumor growth. The present results suggest that the novel compound NO-1886 may suppress carcass weight loss in rats bearing Leydig cell tumor by suppressing the decrease in food consumption and LPL activity.

Adipose Tissue↗
PubMed1998

Pathophysiology of renal fluid retention.

Central to a unifying hypothesis of body fluid regulation is maintenance of arterial circulatory integrity. This may be disturbed by arterial underfilling, either from reduction in cardiac output or by peripheral arterial vasodilation. In cardiac failure (CF), cardiac output falls and the nonosmotic release of arginine vasopressin (AVP) and expression of AVP mRNA in the hypothalamus are stimulated. V2 AVP receptor antagonists correct the impaired water excretion in rats with low-output CF, increase solute free water clearance, correct the hyponatremia in congestive CF patients, and normalize urinary concentrations of the aquaporin-2 (AQP-2) water channels. In conditions associated with peripheral vasodilation, such as cirrhosis, nonosmotic release of AVP also occurs, and AQP-2 gene expression in the rat kidney is up-regulated. In cirrhosis, nitric oxide-mediated vasodilation occurs early prior to water retention. V2 antagonists reverse the latter. In normal pregnancy, plasma AVP is relatively high for the degree of hypoosmolality. Pregnant rats up-regulate AQP-2 in the renal papilla, an effect reversed by V2 receptor antagonists. This supports the hypothesis that AVP is an important mediator of renal water retention in pregnancy. In summary, AVP-mediated water retention through collecting duct AQP-2 water channels is important in both low-output CF and high-output states such as cirrhosis and pregnancy. V2 receptor antagonists reverse the water retention and down-regulate AQP-2 water channels.

Animals↗
PubMed1998

Use of intraperitoneal vessels in reconstructive microsurgery: an account of 117 cases.

The purpose of this study was to evaluate our experience of microvascular anastomosis of intraperitoneal vessels. Between 1985 and 1994, 117 microsurgical reconstructions were done using intraperitoneal vessels. These included oesophageal reconstruction (n = 106), reconstruction of the hepatic arterial, superior mesenteric arterial, or portal venous system (n = 8), and reconstruction of the chest or abdominal wall (n = 3). We used 129 intraperitoneal arteries and 117 intraperitoneal veins. Of a total of 246 intraperitoneal vessels, five hepatic arteries, seven splenic, 14 gastroepiploic, six superior mesenteric, 178 jejunal, 30 ileocolic, four middle colic arteries or veins, and two portal veins were used for microvascular anastomosis. The overall successful rate for these reconstructive cases was 97% (114/117). Microsurgical use of intraperitoneal vessels is a safe and developing procedure in plastic and reconstructive surgery.

Adult↗
PubMed1998

Induction of cyclooxygenase-2 in alveolar macrophages after acid aspiration: selective cyclooxygenase-2 blockade reduces interleukin-6 production.

BACKGROUND: Gastric acid aspiration can result in acute lung injury. In this study, the authors determined whether alveolar macrophages express cyclooxygenase-2 as a source of inflammatory mediators after acid aspiration. METHODS: Seventy-five microliters of hydrochloric acid solution, pH 1.15, was instilled into one lung in mice. After exposure, alveolar macrophages were harvested, and competitive polymerase chain reaction and enzyme-linked immunosorbent assay were performed to measure expression of cyclooxygenase-1 and -2, interleukin-1beta and -6, tumor necrosis factor-alpha, and inducible nitric oxide synthase (iNOS). The authors used immunocytochemistry to demonstrate expression of cyclooxygenase-2 in alveolar macrophages. Selective cyclooxygenase-2 blockade using N-2(-cyclohexyloxy-4-nitrophenyl) methane-sulphonamide was done to characterize prostaglandin-cytokine interaction. RESULTS: Acid aspiration induced upregulation of cyclooxygenase-2 and interleukin-6. Tumor necrosis factor-alpha and iNOS were not upregulated. Interleukin-1beta was upregulated even with saline instillation but could not be detected in the supernatant of the cell culture. Alveolar macrophages harvested from mice instilled with acid showed a trend toward more production of prostaglandin E2 and produced higher concentrations of interleukin-6 compared with alveolar macrophages from mice instilled with saline. Selective cyclooxygenase-2 blockade significantly decreased release of interleukin-6 from alveolar macrophages harvested from mice instilled with acid. CONCLUSIONS: Acid aspiration induces strong expression of cyclooxygenase-2 and production of interleukin-6 in alveolar macrophages. Selective cyclooxygenase-2 blockade reduced production of interleukin-6 by acid-stimulated alveolar macrophages. These studies suggest that the induction of cyclooxygenase-2 plays an important role in the systemic inflammatory response induced by acid aspiration.

Animals↗
PubMed1998

Occult basal cell carcinoma arising in seborrheic keratosis.

The present study reports a case of an occult basal cell carcinoma that arose in seborrheic keratosis. The patient was a fifty-six-year-old male who presented with a dark brown plaque on his back. Clinically, the lesion demonstrated no nodules or ulcerations suggesting that it was malignant. However, histopathological analysis of the lesion revealed an atypical basaloid cell mass that appeared to be a solid basal cell carcinoma beneath and surrounded by a seborrheic keratosis lesion. Thus, the coexistence of basal cell carcinoma and seborrheic keratosis is possible and should be considered when a malignant change in seborrheic keratosis is apparent.

Basal Cell Carcinoma↗
PubMed1998

Gram-negative bacterial infections and cardiovascular parasitism in green sea turtles (Chelonia mydas).

OBJECTIVE: To investigate causes of ill health and mortality in juvenile wild green sea turtles (Chelonia mydas) found along the mid-north west coast of Western Australia between June and October of 1997. PROCEDURE: Department of Conservation and Land Management rangers submitted four dead or dying green sea turtles from separate incidents for veterinary examination, necropsy, and bacteriological, parasitological and histopathological examination. RESULTS: Numerous different species of trematodes belonging to the families Pronocephalidae, Microscaphidiidae and Paramphistomidae were detected in the intestines of two turtles examined, and in all turtles there was severe spirorchid fluke infection including Haemoxenicon sp, Amphiorchis sp and Hapalotrema sp. Histopathological examination demonstrated severe multifocal to diffuse granulomatous vasculitis, aggregations of spirorchid fluke eggs and microabscesses throughout various tissues including intestines, kidney, liver, lung and brain. Cultures and or histopathological examination demonstrated disseminated Gram-negative bacterial infections including salmonella, E coli, Citrobacter freundii and Moraxella sp. CONCLUSION: Infections caused by salmonellae, E coli and other Gram-negative bacteria should be considered as causes of systemic illness and death in wild green sea turtles infected with spirorchid cardiovascular flukes and other internal parasites.

Animals↗
PubMed1998

Evaluation of antimicrobial and lipopolysaccharide-neutralizing effects of a synthetic CAP18 fragment against Pseudomonas aeruginosa in a mouse model.

CAP18 (cationic antimicrobial protein; 18 kDa) is a neutrophil-derived protein that can bind to and inhibit various activities of lipopolysaccharide (LPS). The 37 C-terminal amino acids of CAP18 make up the LPS-binding domain. A truncated 32-amino-acid C-terminal fragment of CAP18 had potent activity against Pseudomonas aeruginosa in vitro. We studied the antimicrobial and LPS-neutralizing effects of this synthetic truncated CAP18 peptide (CAP18106-137) on lung injury in mice infected with cytotoxic P. aeruginosa. To determine its maximal effect, the CAP18106-137 peptide was mixed with bacteria just prior to tracheal instillation, and lung injury was evaluated by determining the amount of leakage of an alveolar protein tracer (125I-albumin) into the circulation and by the quantification of lung edema. The lung injury caused by the instillation of 5 x 10(5) CFU of P. aeruginosa was significantly reduced by the concomitant instillation of CAP18106-137. However, the administration of CAP18106-137 alone, without bacteria, induced lung edema, suggesting that it has some toxicity. Also, the peptide did not significantly reduce the number of bacteria that had been simultaneously instilled, nor did it significantly improve the survival of the infected mice. The addition of CAP18106-137 to aztreonam along with the bacteria did decrease the level of antibiotic-induced release of inflammatory mediators including tumor necrosis factor alpha, interleukin-6, and nitric oxide and also improved the survival of the mice. Therefore, more investigations are needed to confirm the toxicities and the therapeutic benefits of CAP18106-137 as an adjunctive therapy to antibiotics in the treatment of infections caused by gram-negative bacteria.

Animals↗
PubMed1998

In vitro cellular toxicity predicts Pseudomonas aeruginosa virulence in lung infections.

The role of quorum sensing by Pseudomonas aeruginosa in producing cytotoxicity has not been fully investigated. Strains of P. aeruginosa have been characterized as having an invasive or a cytotoxic phenotype (S. M. J. Fleiszig et al., Infect. Immun. 65:579-586, 1997). We noted that the application of a large inoculum of the invasive strain 6294 caused cytotoxicity of cultured epithelial cells. To investigate this dose-related cytotoxicity, we compared the behavior of 6294 to that of another invasive strain, PAO1, and determined whether the cytotoxicity could be related to quorum sensing. Both invasive strains, 6294 and PAO1, appear to have quorum-sensing systems that were operative when large doses of bacteria were applied to cultured lung epithelial cells or instilled into the lungs of animals. Nonetheless, only 6294 was cytotoxic. Cytotoxicity induced by 6294 correlated with increased elastase production. These experiments suggest that there are multiple mechanisms for the induction of cytotoxicity, pathology, and mortality in vivo. However, in vivo cytotoxicity and mortality, but not pathology, could be predicted by quantitative in vitro cellular damage experiments utilizing a range of bacteria-to-cell ratios. It appears that quorum sensing may inversely correlate with virulence in that strains that produced PAI [N-(3-oxododecanoyl) homoserine lactone] also appeared to attract more polymorphonuclear leukocytes in vivo and were possibly eliminated more quickly. In addition, exoproduct production in bacteriological medium in vitro may differ significantly from exoproduct expression from infections in vivo or during cocultivation of bacteria with tissue culture cells.

4-Butyrolactone↗
PubMed1998

[Current topics in the regulation of prostanoids-1. Inducible cyclooxygenase COX-2 and selective blockers].

Cyclooxygenases (COX) are prostaglandin synthases and are the main therapeutic targets for non-steroidal anti-inflammatory drugs. Recently it has been established that apart from the constitutive isoform, an inducible isoform of this enzyme is upregulated after injurious stimuli. The structures of the genes encoding these enzymes and protein structures have been determined, and with the utilization of knockout mice, the physiological properties of each isozyme are being revealed. COX-1 is responsible for the production of physiological levels of prostanoids, whereas COX-2 is upregulated during inflammatory states and produces prostanoids responsible for the generation of fever, pain or other inflammatory responses. Selective COX-2 blockers may be a safe and useful alternative in the treatment of inflammatory disorders, pain, and fever.

Animals↗
PubMed1998

[Current topics in the regulation of prostanoids--2. The interaction with cytokines and nitric oxide].

Cyclooxygenase (COX)-2 is induced by proinflammatory cytokines such as interleukin (IL)-1 beta, cytokines produced from helper T cell subpopulation Th 1, such as interferon-gamma and tumor necrosis factor-beta. Cytokines produced by the T cell such as IL-4, IL-10, and IL-13 down-regulate induction of COX-2. The novel MAP kinase pathway, JNK and/or p 38, are important intracellular signaling pathways for induction of COX-2. The increased production of prostaglandin E2 by upregulation of COX-2 increases IL-6 production. By utilizing a COX-2 blocker, it is possible to decrease IL-6 production via reduction of prostanoid production, thereby attenuating the systemic inflammatory response. Nitric oxide (NO) and prostanoids are also known to interact and regulate each other. It is important to note the interactions between prostanoids and cytokines or other inflammatory mediators such as NO in understanding the mechanism of the anti-inflammatory effects of prostanoid regulation.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1997

IL-10 improves lung injury and survival in Pseudomonas aeruginosa pneumonia.

Pseudomonas aeruginosa is the most frequent Gram-negative pathogen causing nosocomial pneumonia. Four different strains of P. aeruginosa (including three isogenic transposon mutants) were utilized in experiments in mice to characterize the specific patterns of cytokine generation in response to bacterial products and cytotoxicity. Intratracheal instillation of any of the strains led to the up-regulation of IL-1beta, IL-6, and TNF-alpha mRNA. Instillation of the cytotoxic strains (PA103, PA103tox::omega) led to IL-10 mRNA up-regulation in the lungs and increased concentrations of IL-10 in the blood. In contrast, the instillation of the noncytotoxic strains (PA01, PA103exsA::omega) did not lead to an increase in IL-10 mRNA in the lungs or to an increase of IL-10 concentration in blood. IL-10 production appears to be a response to either cellular injury or to specific cytotoxic exoproducts produced by the bacteria. The systemic administration of rIL-10 significantly decreased the lung injury and the mortality in mice who had received the cytotoxic strains. The improvement in survival induced by administration of rIL-10 required the concomitant presence of IFN-gamma, as blockade of IFN-gamma with a neutralizing Ab led to 100% mortality, despite the administration of rIL-10. These results suggest that IL-10 is produced in response to specific bacterial products and that there is a potential role for IL-10 in the treatment of cytotoxic P. aeruginosa pneumonia.

Animals↗