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N Ohtani

Publications and source records attributed to N Ohtani.

69 records · Page 4Linked to original sources

[Phase II study with methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) in hematological malignancies].

Forty-two cases of hematological malignancy (18 cases of CML, three cases of polycythemia vera, 10 cases of malignant lymphoma and 11 cases of multiple myeloma) were treated with MCNU. The results obtained were as follows. MCNU was markedly effective on CML cases, being especially useful during the chronic phase, and a partial remission was observed in one of three patients with CML blastic crisis. A good response was observed in all cases with polycythemia vera. In some cases of malignant lymphoma, a fair response was observed. No response was observed in any of the cases of multiple myeloma. Myelosuppression was a major side effect of MCNU, but other side effects other than melena were not severe.

Adult↗

[Experimental and clinical studies on enzymes of mitochondria in various liver diseases; with special reference to alcoholic liver disease (author's transl)].

Mitochondrial enzymes in rat livers or intestines were investigated in experimental models with ethanol- or other hepatotoxic agent-induced liver injuries and extrahepatic cholestasis. In clinical experiment, activities of mitochondrial GOT (mGOT) and ornithine carbasmyl transferase (OCT) were examined in alcoholisms and patients with other various liver diseases. Results obtained are as follows; 1) The activities of OCT and mGOT were increased particularly at onset of acute hepatitis, in chronic active hepatitis and intrahepatic cholestasis, showing that mitochondria were injured strikingly in these diseases. The activities in alcoholics were not so great, however mGOT/total-GOT ratio was increased in level than in other diseases. 2) Changes in mitochondrial enzymes of rat liver treated with ethanol were too varied to catch the actual tendency in this pathologic state. 3) Administration of galactosamine, carbon tetrachloride, or alpha-naphthyl isothiocyanate (ANIT) caused a significant fall in activities of succinate cytochrome C reductase and OCT, along with increase in serum activity of OCT, indicating severe mitochondrial injury with these drugs. Extrahepatic cholestasis following bile duct ligation showed the same changes of mitochondrial enzymes in liver tissue and serum. 4) These data indicate that observation of activities of serum OCT, mGOT, along with mGOT/total-GOT ratio are useful for estimation of mitochondrial damage in extra- and intra-hepatic cholestasis, and acute or chronic active hepatitis. The changes in alcoholic fatty liver was not so subtle as compared with other liver diseases. 5) It is surmized that smooth endoplasmic reticulum was increased in content and pentose phosphate shunt was inhibited by chronic ethanol treatment, estimating from increased activities of NADH-ferricyanide reductase and gamma-glutamyl transpeptidase, and decreased activity of glucose-6-phosphate dehydrogenase. 6) The changes in hepatic enzymes with ethanol treatment were paralleled with those of intestinal ones, indicating that metabolic changes in intestine contribute someway in the formation of alcoholic fatty liver. 7) Chronic ethanol treatment induced lowered active transport in intestinal mucosa, which indicates inhibition in absorption of various nutrients by ethanol.

1-Naphthylisothiocyanate↗

Time-course of left atrial performance during coronary artery occlusion followed by reperfusion in anesthetized dogs by densitometric analysis of digital atrioventriculographic images.

The left atrial (LA) function during coronary artery occlusion followed by reperfusion using densitometric analysis of digital atrioventriculographic images was evaluated. Eight anesthetized dogs underwent atrioventriculography at baseline, 10 and 60 min after left circumflex coronary artery (LCX) occlusion and 5, 30, 60, and 120 min of reperfusion. Time-density curves were obtained for LA and left ventricle (LV). The ratios of passive atrial video-densitometric change (VC) to total VC (Passive Ratio), and active VC to total VC (Active Ratio) were calculated. Left ventricular ejection fraction (LVEF), peak ejection rate (PER), and peak filling rate (PFR) were derived. Active Ratio, an index of atrial contraction, increased to 144%, and Passive Ratio decreased to 75% of baseline at 60 min of LCX occlusion. Two hours after reperfusion, both Active and Passive Ratios returned to control level. While LVEF reduced to 70%, PER to 67%, LV peak positive dP/dt to 88% of baseline at 60 min after occlusion, and remained depressed at 2 h after reperfusion. However, PFR, LV peak negative dP/dt and LV isovolumic pressure decay rate showed recovery at 2 h after reperfusion. There were significant correlations between PFR and Passive Ratio (r = 0.41), and between Active and Passive Ratios (r = 0.55). Thus, time-course of recovery of LV post-ischemic systolic and diastolic function was different. Return of LA function to control level during 2 h after reperfusion may be depend on recovery of LV diastolic function.

Animals↗

Small bowel transplantation induces adrenergic hypersensitivity in ileal longitudinal smooth muscle in rats.

Our aim was to determine the effects of small bowel transplantation on contractility of longitudinal muscle in the rat ileum. Full-thickness longitudinal muscle strips from four groups of rats (naive controls, sham-operated controls, and 1 week and 8 weeks after syngeneic orthotopic small bowel transplantation) were studied in vitro. Neither baseline contractility nor response to neural blockade (tetrodotoxin) or adrenergic/cholinergic blockade differed among the groups. Although the dose response to the cholinergic agonist bethanechol and to nitric oxide did not differ among groups, the ED50 (negative log of concentration giving half-maximal effect) for the adrenergic agonist norepinephrine was increased l week and 8 weeks after transplantation, indicating a hypersensitivity response not blocked by tetrodotoxin. Nonadrenergic, noncholinergic inhibitory responses to electrical field stimulation were of greater amplitude and occurred at lesser frequencies (>/=5 Hz) 1 week after small bowel transplantation, but returned to control values 8 weeks postoperatively. These inhibitory responses were blocked by the nitric oxide synthase inhibitor L-NMMA but not by methylene blue, a nonspecific inhibitor of guanylate cyclase. Small bowel transplantation induces a persistent adrenergic denervation hypersensitivity at the muscle and appears to upregulate, at least transiently, other inhibitory mechanisms mediated by neural release of nitric oxide. Small bowel transplantation does not alter muscle response to cholinergic pathways. These alterations in smooth muscle contractility may affect gut function early after clinical small bowel transplantation.

Animals↗

Nitric oxide pathways in circular muscle of the rat jejunum before and after small bowel transplantation.

Previous studies suggest that nitric oxide synthase is upregulated after small bowel transplantation which may have implications in enteric dysfunction after small bowel transplantation. The aim of this study was to determine the role of nitric oxide in nonadrenergic, noncholinergic inhibitory function after small bowel transplantation in rat jejunal circular muscle. The following four groups of rats (n = >/=8 rats per group) were studied: Neurally intact control animals; 1 week after anesthesia and sham celiotomy, and either 1 week or 8 weeks after isogeneic, orthotopic small bowel transplantation. Full-thickness jejunal circular muscle strips were evaluated under isometric conditions for spontaneous contractile activity, response to electrical field stimulation, and effects of exogenous nitric oxide and nitric oxide antagonists. Spontaneous activity did not differ among groups. Electrical field stimulation inhibited activity similarly in all groups. Exogenous nitric oxide, NG-monomethyl L-arginine monoacetate salt (a nitric oxide synthase inhibitor), and methylene blue (cGMP antagonist) had no effect on spontaneous activity. Neither nitric oxide antagonist altered the inhibitory response to neural excitation by electrical field stimulation in any group. Nitric oxide, a known inhibitory neurotransmitter in other gut smooth muscle, has no apparent role in rat jejunal circular muscle before or after small bowel transplantation.

Animals↗

Chronic diversion of bile to the urinary bladder induces pancreatic growth in dogs.

The aim of this study was to elucidate the mechanism of chronic biliary diversion and its effect on pancreatic growth. In the first part of the study, nine mongrel dogs underwent diversion of bile from the gastrointestinal tract by ligating the common bile duct and interposing a segment of jejunum between the gallbladder and the urinary bladder (cholecystojejunocystostomy [CJC]). Despite the loss of 7% of their body weight at 12 weeks after bilioenteric diversion, CJC dogs had significantly greater pancreatic wet weight than control dogs (51.2 +/- 2.2 g vs. 37.1 +/- 2.2 g). In the second part of the study, six other dogs underwent CJC. Twelve weeks later, bilioenteric continuity was restored by creating a cholecystojejunoduodenostomy (CJD). The dogs were given butter (3 g/kg) by mouth (prior to surgery, 12 weeks after CJC, and 4 weeks after CJD). Pancreatic excisional biopsy specimens were obtained at each operation and at autopsy. CJC induced more pancreatic RNA per milligram of weight (743 +/- 52, CJC; 579 +/- 44, prior to surgery, P <0.05 vs. CJC; 520 +/- 26 microg/100 mg tissue, CJD, P <0.01 vs. CJC), but not more DNA, and significantly higher basal plasma cholecystokinin levels and butter-stimulated cholecystokinin responses when compared with values prior to surgery or following CJD. We conclude that chronic biliary diversion induces pancreatic growth associated with hypersecretion of cholecystokinin in dogs.

Animals↗

Mediators for fat-induced ileal brake are different between stomach and proximal small intestine in conscious dogs.

Our aim was to determine the mechanisms by which intraileal fat alters proximal gastrointestinal motility--the ileal brake. Five mongrel dogs with ileal Thiry-Vella fistulas were equipped with strain gauge force transducers on the upper gut to measure contractile activity. Ileal infusions of 115 mmol/L oleic acid and triglyceride were studied in dogs with extrinsically innervated and extrinsically denervated Thiry-Vella loops. Plasma concentrations of peptide YY and total glucagon-like immunoactivity were measured. Oleic acid but not triglyceride inhibited postprandial contractions in the gastric antrum in dogs with innervated and denervated Thiry-Vella loops. Postprandial duodenal and jejunal motility was inhibited by oleic acid regardless of extrinsic denervation to the loops (P <0.05), but triglyceride inhibited small intestinal motility only in dogs with innervated Thiry-Vella loops. Intraileal oleic acid but not triglyceride increased plasma concentrations of peptide YY and total glucagon-like immunoactivity in dogs with innervated and denervated Thiry-Vella loops. Intraileal oleic acid inhibits gastric and small intestinal motility possibly via increased plasma concentrations of peptide YY and enteroglucagon. Intact extrinsic innervation is necessary for intraileal triglyceride to inhibit small intestinal motility.

Animals↗

Effect of ileojejunal transposition on gastrointestinal motility, gastric emptying, and small intestinal transit in dogs.

There is speculation that enteroglucagon and peptide YY are responsible for mediating the < > known as a suppressive reaction of upper gastrointestinal motility and transit that is induced by the infusion of nutrients into the ileum. We studied changes in motility and transit in dogs with ileojejunal transposition in which the distal ileum is exposed to undigested nutrients. Nine adult mongrel dogs were equipped with strain gauge force transducers placed on the gastric body, antrum, duodenum, and proximal jejunum. Measurements of gastrointestinal motility, gastric emptying, and plasma levels of total glucagon-like immunoreactivity, immunoreactive glucagon, and peptide YY were obtained both before and after either ileojejunal transposition (5 dogs) or sham operation (4 dogs). Postprandial contractions in the gastric antrum and gastric emptying were significantly inhibited after ileojejunal transposition. The inhibitory effect of ileojejunal transposition on antral motor activity was found to correlate with the rise in plasma total glucagon-like immunoreactivity and peptide YY concentrations. However, plasma glucagon levels were unaffected by ileojejunal transposition. These results suggest that hypersecretion of enteroglucagon and peptide YY induced by ileojejunal transposition inhibits postprandial gastric motor function.

Animals↗

Progression of prostate cancer: diagnostic and prognostic utility of prostate-specific antigen, alpha2-macroglobulin, and their complexes.

We previously reported cases of advanced prostate cancer (PCa) in which serum alpha2-macroglobulin (alpha2M) levels were markedly decreased to less than approximately 50 mg/dl whereas serum prostate-specific antigen (PSA) levels were remarkably increased. These cases were not complicated with disseminated intravascular coagulation (DIC). In this study, we measured serum PSA and alpha2M in 108 patients with either benign prostatic hyperplasia (BPH) or PCa to elucidate the relationship between PSA, i.e. the serum protease derived from the prostatic tissue, and alpha2M, i.e. the protease inhibitor that was the most abundantly contained in serum. alpha2M was determined by ELISA, total PSA and PSA-alpha1-antichymotrypsin (PSA-ACT) by EIA, and free-PSA by RIA in 44 patients with untreated BPH and 64 patients with untreated PCa. The ready association of alpha2M and PSA was assessed using Western blotting to identify complexes of the two. Levels of total serum PSA correlated positively with those of PSA-ACT in PCa (r = 0.99, p < 0.001), and both levels increased with advancing stage of disease. In contrast, the serum-free PSA/total PSA ratio (free/total PSA) and alpha2M levels decreased as the disease progressed. However, only the free/total PSA ratio attained significant difference for localized cancer in stage T1,2 versus BPH (p < 0.05). In stage M1b PCa, in which serum PSA levels were very high, there was a negative correlation between the total PSA and alpha2M values (r = -0.57, p < 0.05). In addition, serum alpha2M levels tended to decrease with progression of PCa. Serum total PSA levels correlated tightly with serum PSA-ACT levels. It is suggested that PSA is usually complexed with ACT in the serum. Free/total PSA was useful for differential diagnosis between early cancer and BPH. Levels of serum alpha2M of less than 50 mg/dl in PCa patients may indicate a possibility of bone metastases.

Aged↗

Levels of alpha 2 macroglobulin can predict bone metastases in prostate cancer.

BACKGROUND: In prostate cancer, we previously reported that a marked decrease of serum alpha 2 macroglobulin (alpha 2M) to less than approximately 50 mg/dl was associated with the presence of bone metastases. In order to investigate the relationship between bone metastases and alpha 2M, we assessed these two parameters in 128 patients with prostatic diseases. MATERIALS AND METHODS: 66 patients with untreated benign prostatic hypertrophy and 62 with untreated prostate cancer were included in the study. Measurement of alpha 2M concentration was performed by Laser-Nephelometry, prostate-specific antigen (PSA) by EIA. RESULTS: The serum alpha 2M levels in prostate cancer with bone metastases showed a significantly lower level compared with the group without bone metastases (p < 0.01). Cases with serum alpha 2M levels of less than 50 mg/dl all had bone metastases. Serum alpha 2M levels were inversely related to PSA levels in stage M1b disease. CONCLUSIONS: Measurement of serum alpha 2M levels may be useful for the diagnosis and follow up of bone metastases in prostate cancer.

Adenocarcinoma↗