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Biomedical subjects

S Inoue

Publications and source records attributed to S Inoue.

At least 37 records · Page 2Linked to original sources

Alpha 2-adrenergic modulation of pancreatic glucagon secretion in rats.

The present study was designed to clarify the mechanism of adrenergic modulation of pancreatic glucagon secretion in rats under physiological conditions by 1) epinephrine infusion alone or together with adrenergic blockers and 2) administration of adrenergic agonists. Intravenous infusion of epinephrine alone (1 microgram/kg/min, equal to 0.7 nmol/kg/min) caused a significant increase in glucagon secretion. Phentolamine (an alpha blocker) or yohimbine (an alpha 2 blocker) administration completely inhibited the increase of glucagon secretion caused by epinephrine infusion, but neither the administration of bunazosin (an alpha 1 blocker) nor beta blockers inhibited it. Infusion of clonidine (an alpha 2 agonist) caused significant increase of glucagon secretion even at a low dose of 0.5 nmol/kg/min, although infusion of neither an alpha 1 nor a beta 2 agonist caused it even at the high dose of 40.0 nmol/kg/min. It is concluded that the alpha 2 receptor mechanism plays the most important role in the adrenergic modulation of glucagon secretion in rats under physiological conditions.

Adrenergic alpha-Agonists

The incidence of Listeria species in retail foods in Japan.

Meat, fish and vegetable products obtained at retail shops in or around Tokyo were examined for Listeria contamination. Listeria spp. were isolated from 43 (56.6%) out of 76 samples of meat products. L. monocytogenes occurred in 26 (34%) of the samples, L. monocytogenes was isolated from 7 (6.1%) out of 114 samples of fish and fish products including 'ready-to-eat' foods. Listeria was not isolated from any of 21 samples of vegetable and vegetable product including 'ready-to-eat' foods investigated.

Fish Products

Hypersecretion of IAPP from the islets of VMH-lesioned rats and obese Zucker rats.

To investigate the possible role of islet amyloid polypeptide (IAPP) in the development of type 2 diabetes mellitus, we examined the IAPP content and secretion in pancreatic islets isolated from ventromedial hypothalamic (VMH)-lesioned rats and genetically obese Zucker rats, using a specific radioimmunoassay for IAPP. Obesity and hyperinsulinemia were observed in rats 21 days after VMH lesioning. IAPP content was increased in the islets of VMH-lesioned rats compared with findings in the sham-operated controls (100.9 +/- 6.6 vs 72.8 +/- 3.85 fmol/islet; P less than 0.01). Isolated islets of VMH-lesioned rats secreted larger amounts of IAPP in the presence of 2.8 and 16.7 mM glucose (2.99 +/- 0.98 and 11.2 +/- 0.29 fmol islet-1 3 h-1) than was noted in sham-operated rats (ND and 6.65 +/- 0.78 fmol islet-1 3 h-1). In the obese Zucker rats, aged 14 weeks, IAPP concentrations in the islets were elevated compared with lean rats (133.3 +/- 10.6 vs 84.4 +/- 8.5 fmol/islet; P less than 0.01). The isolated islets secreted larger amounts of IAPP in response to 2.8 and 16.7 mM glucose (2.83 +/- 0.88 and 15.81 +/- 1.35 fmol islet-1 3 h-1) than did those from lean control rats (0.36 +/- 0.19 and 12.49 +/- 1.20 fmol islet-1 3 h-1). These results strongly suggest that overproduction and hypersecretion of IAPP occur in animals with obesity and hyperinsulinemia.

Amyloid

Diagnostic significance of nuclear DNA content and nuclear area in oral hyperplasia, dysplasia, and carcinoma.

The nuclear DNA content and the nuclear area in hyperplasia, dysplasia, and carcinoma of the oral cavity were quantitatively analyzed by microspectrophotometry. In carcinoma, marked variability of the nuclear DNA content and the nuclear area was found. The mean nuclear DNA content, the variance of the nuclear DNA content, the frequency of cells above tetraploid (4 C), the mean nuclear area, and the variance of nuclear area in hyperplasia and dysplasia were significantly different from these values with carcinoma. In some cases of leukoplakia and verrucous hyperplasia with subsequent malignant formation, the values were beyond the lower limit of carcinoma. The results suggest that the nuclear DNA and the nuclear area are important objective indices for predicting malignant potential of precancerous lesions.

Carcinoma, Squamous Cell

Effects of isopropanol on the development of inflammatory reactions in rats.

The effects of isopropanol on the development of inflammation were studied in rats. Isopropanol inhibited both the histamine-induced increase in cutaneous vascular permeability and the carrageenan-induced plasma exudation into the pleural cavity. The lipopolysaccharide-induced leucocyte emigration into the subcutaneous pouch was unaffected by isopropanol, but the leucocyte emigration of carrageenan-induced pleural inflammation was markedly inhibited by isopropanol. In contrast, when isopropanol was administered with an anti-inflammatory drug (indomethacin or dexamethasone), it enhanced the pleural inflammatory reaction. These results suggest that isopropanol may exert toxic effects through interference with the normal processes of inflammation and interaction with other agents that affect inflammatory reactions.

1-Propanol

Elevated content and secretion of gut GLI in VMH-lesioned rats.

Gut glucagon-like immunoreactivity (GLI), a supposed intestinal growth factor in the plasma and gastrointestinal tract, and weight of the gastrointestinal tract, an intestinal growth indicator, were examined in ventromedial hypothalamic (VMH)-lesioned rats 1 week after VMH lesions. Postprandial plasma gut GLI in VMH-lesioned rats was significantly higher than that in control rats. The content of gut GLI in all gastrointestinal sections except the duodenum in VMH-lesioned rats was significantly greater than that in control rats. Gel chromatography in the lower portion of the small intestine in which GLI content was the highest of all sections revealed the same pattern in both VMH-lesioned and control rats with two peaks of similar molecular size. Weight of all gastrointestinal sections except the cecum in VMH-lesioned rats significantly increased. These results demonstrated that both gut GLI secretion and production were enhanced in VMH-lesioned rats. The elevated gut GLI release may accelerate growth of the gastrointestinal tract in these animals.

Animals

QRS complex changes in the V5 ECG lead during cardiac surgery.

The QRS complex in lead V5 was studied during cardiac surgery. R wave amplitude decreased after induction of anesthesia to approximately 50% to 60% of the preanesthetic level before the institution of CPB (P < 0.001). An rS complex appeared immediately after cardioversion and changed in configuration to an Rs complex 15 to 30 minutes after aortic declamping. The R wave continued to recover toward the preanesthetic level at sternal closure. Patients with coronary artery disease had a poorer recovery of the R wave (P < 0.05) than patients with valvular heart disease; the former recovered to only 50% of the preanesthetic level at sternal closure. Nonsurvivors had much smaller R waves (26.1 +/- 20.5%) than survivors (P < 0.001). The R wave peaked 30 to 40 ms after initiation of the QRS complex, which indicates recovery of conductivity and the activation sequence of the left ventricular (LV) free wall, which is easily disturbed by hypothermia, cardioplegia, and ischemia during aortic cross-clamping. Monitoring QRS complex changes in lead V5 appears to be important on weaning from cardiopulmonary bypass to detect regional ischemia, and also to observe electrophysiologic recovery of the LV free wall.

Adult

Clinical and basic aspects of an anorexiant, mazindol, as an antiobesity agent in Japan.

The Japanese Mazindol study group investigated the action of an anorexiant, mazindol, and found that it reduced food intake by directly suppressing neurons in the lateral hypothalamus, inhibited gastric acid secretion, increased motor activity, decreased glucose absorption, and inhibited insulin secretion. It thus appears that the main effect of mazindol is to decrease food intake through suppressing feeding centers in the hypothalamus. A multicenter open study of mazindol in Japan revealed that loss of body weight and relative body weight in 14 wk were 4.6 kg and 9.2%, respectively, with suppression of appetite in the majority of obese patients. A multicenter double-blind study demonstrated that mazindol was superior to the placebo in the treatment of simple obesity. We also suggest that mazindol is effective in the maintenance of reduced body weight after obesity therapy and in the treatment of obesity-related diseases such as diabetes, hypertension, or hyperlipidemia.

Animals

Very-low-calorie-diet therapy in severe obesity.

This study investigated the effects of very-low-calorie-diet (VLCD) therapy on body weight, plasma glucose, and lipid metabolism in severely obese patients. Ninety-one patients were subjected to VLCD therapy for 4-24 wk. Reduction of body weight was remarkable during the first 4 wk, then leveled off despite continuous treatment. Fasting plasma glucose, triglyceride, and 75-g oral glucose-tolerance test showed a significant improvement. Total cholesterol fell in the early stages but then increased more than the pretreatment level during VLCD. VLCD therapy is useful for the treatment of severe obesity.

Adult

Caffeic acid causes metal-dependent damage to cellular and isolated DNA through H2O2 formation.

Pulsed field gel electrophoresis showed that caffeic acid induced DNA strand breaks in cultured human cells in the presence of Mn(II). With alkali treatment, DNA single-strand breaks were observed. The strand breakage was increased by the treatment of buthionine sulphoximine (a GSH synthesis inhibitor) and 3-aminotriazol (a catalase inhibitor) and decreased by catalase, indicating the involvement of H2O2. The DNA damage was decreased by o-phenanthroline, indicating the involvement of transition metal ion. Damage to isolated DNA from c-Ha-ras-1 protooncogene was investigated by a DNA sequencing technique. Caffeic acid caused DNA damage in the presence of Cu(II) but not in the presence of either Mn(II) or Fe(III). Caffeic acid plus Cu(II) induced piperidine-labile sites frequently at thymine residues, especially of the 5'-GTC-3' and 5'-CTG-3' sequences. Typical OH scavengers showed no inhibitory effects. The inhibitory effects of bathocuproine and catalase on Cu(II)-mediated DNA damage suggest that Cu(I) and H2O2 have important roles in the production of active species causing DNA damage. The Cu(II)-mediated DNA damage was enhanced by pre-incubation of caffeic acid with Mn(II). Mn(II)- or Cu(II)-catalyzed autoxidation of caffeic acid produced H2O2 with efficiency of Mn(II) greater than Cu(II). These results suggest that in the presence of Mn(II) or Cu(II), caffeic acid produces H2O2, which is activated by transition metals to cause damage to DNA in vitro and probably in cultured cells.

Amitrole

Kinetics of the hydrolysis of micellar substrates catalyzed by snake venom phospholipases A2.

Effects of Ca2+ on the kinetic parameters for the hydrolysis of mixed micelles of 1,2-dipalmitoyl-sn-glycero-3-phosphorylcholine (diC16PC) with Triton X-100, catalyzed by a cobra (Naja naja atra) (Group I) and a Habu (Trimeresurus flavoviridis) (Group II) PLA2s, were studied and compared with the results reported for other Group I and II enzymes. The substrate bindings to Group I enzymes were independent of the Ca2+ binding, whereas the substrate bindings to Group II enzymes were facilitated more than 10 times by the Ca2+ binding to the enzymes. The result for Group II enzymes, but not Group I enzymes, seemed compatible with the hypothesis for interpreting the catalytic mechanism that an intermediate complex should be stabilized by the coordination of the bound Ca2+ with the phosphoryl group and the carbonyl oxygen atom of the ester bond at the sn-2 position of the bound substrate molecule [Verheij et al. (1980) Biochemistry 19, 743-750 and (1981) Rev. Physiol. Biochem. Pharmacol. 91, 91-203]. The pH dependence of the kinetic parameters for the hydrolysis of the mixed micellar diC16PC, catalyzed by the cobra (N. naja atra) (Group I) and Habu (T. flavoviridis) (Group II) PLA2s, was also studied. The pK values of the catalytic group, His 48, and Tyr 52 for N. naja atra PLA2, shifted from 7.25 to 7.70 and from 10.30 to 10.85, respectively, and the corresponding values for T. flavoviridis PLA2 shifted from 5.80 to 6.95 and from 10.10 to 10.76, respectively, on binding of the micellar substrates to the enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Flow cytometric analyses of the characteristics of tumor cells treated with two platinum compounds: 1,1-cyclobutanedicarboxylato(2-aminomethylpyrrolidine)- platinum(II) and cisplatin.

In order to reduce the toxicities of cisplatin (DDP) and/or to improve antitumor efficacy, a large number of new platinum analogues have been synthesized. 1,1-Cyclobutanedicarboxylato(2-aminomethylpyrrolidine)platin um(II) (DWA2114R) is one of them. In this study, we characterized the action mechanism of DWA2114R flow-cytometrically in 3 human lung cancer cell lines by using bromodeoxyuridine (BrdUrd), rhodamine 123 (Rho) and Ki-67 antibody (Ab), and compared the results with those for DDP. We found that the actions of these 2 platinum analogues were characteristically different at the subcellular level. Our observations may be summarized as follows. a) Simultaneous exposure of cells to DDP and BrdUrd resulted in decreases in fluorescence intensity, i.e. in the amount of BrdUrd incorporated into single-stranded DNA. b) DDP appears to be approximately 20-fold more active than DWA2114R in producing cell cycle perturbation. c) In PC-6 small cell carcinoma cells, DDP induced decreases in S phase cells and accumulation of cells in the G2M phase, whereas in PC-10 squamous carcinoma and PC-3 adenocarcinoma cells DDP produced S phase cell accumulation. Weak but similar changes occurred with DWA2114R. d) The high Ki-67 antigen cell population was decreased by treatment with either DDP or DWA2114R, but DDP reduced the low Ki-67 antigen population more than DWA2114R. e) In PC-10 and PC-6 cells, DDP suppressed Rho incorporation into live mitochondria, whereas DWA2114R produced no change in Rho incorporation. PC-3 cells were not affected by either DDP or DWA2114R. It is likely that these differences reflect the biological activities of DDP and DWA2114R.

Antineoplastic Agents

Jejunal perforation associated with cytomegalovirus infection in a patient with adult T-cell leukemia-lymphoma.

A patient with adult T-cell leukemia-lymphoma suffered a jejunal perforation, which we believe was directly attributable to cytomegalovirus (CMV) infection. In the areas of ulceration and perforation in the small bowel, blood vessels penetrating the muscularis propria showed extensive lining of cytomegalic endothelial cells with CMV inclusions, accompanied by occasional disruption of the walls, partial occlusion of the lumina, fibrin thrombi, and hemorrhage. The CMV-induced vascular damage seemed to be closely related to the occurrence of ulcers and perforation. The recognition of CMV as a cause of lethal gastrointestinal lesions in immunocompromised hosts has become more important with the advent of anti-CMV therapy.

Adult

An autopsy case of Kawasaki disease with reference to occurrence of acute coronary thrombosis in the convalescent stage.

A one-year, four month-old boy who had suffered from Kawasaki disease died suddenly during convalescence despite intensive gamma-globulin treatment. Autopsy revealed a) sausage-like aneurysms of the left and right coronary arteries and fresh thrombosis in the right coronary aneurysm, b) fresh transmural myocardial necrosis in the whole wall of the left ventricle and the anterior part of the wall of the right ventricle, and c) swelling of the cervical lymph nodes and thymus (60 g). Histologically, fibrocellular thickening of the intima and destruction of the media and internal elastic lamina were conspicuous in the area of the aneurysm, but those of the intima and media in the areas adjacent to the aneurysm were mild. Abrupt narrowing of the lumen at the border between the aneurysm and periphery of the right coronary artery was detected, and this may have been responsible for formation of the thrombus in the right coronary aneurysm. In the systemic arteries, perivascular fibrosis was very noticeable despite less severe injury to the intima and media. These findings suggest that severe inflammation of the periarterial regions was present in the acute phase. The lymph system still showed inflammation, supporting the infectious or toxic nature of Kawasaki disease.

Acute Disease

Inhibitory effects of polyethers on human immunodeficiency virus replication.

We examined the inhibitory activities of 10 polyether antibiotics on human immunodeficiency virus (HIV) type 1. These compounds caused concentration-dependent inhibition of HIV replication in primary infected cultures of human T-lymphoblastoid H9 cells. The ratio of 50% effective concentrations for cellular cytotoxicity (MTT assay) to antiviral activity (reverse transcriptase assay) was over 5. Anti-HIV activity was also observed in cultures of monocytic lineage U937 cells chronically infected with HIV.

Anti-Bacterial Agents

Hepatocellular carcinoma: treatment with percutaneous ethanol injection and transcatheter arterial embolization.

The therapeutic effectiveness of a new combination therapy--pretreatment with transcatheter arterial embolization (TAE) and subsequent percutaneous ethanol injection (PEI)--for solitary large (> 3.0 cm in diameter) primary hepatocellular carcinoma lesions was compared with that of TAE alone. With TAE alone, a partial response of the tumor was seen in only 10% of the patients, and the 1-, 2-, and 3-year survival rates were calculated to be 68%, 37%, and 0%, respectively. Histologic examination of specimens obtained at hepatectomy showed that TAE alone caused complete necrosis in only 20% of the tumors. In contrast, PEI combined with TAE significantly (P < .05) increased the partial response rate (45%) and significantly (P < .01) prolonged the 1-, 2-, and 3-year survival rates (100%, 85%, and 85%, respectively). Combination therapy caused complete histologic necrosis in 83% of the tumors. It also was significantly (P < .05) better than TAE alone in terms of rate of primary tumor recurrence during follow-up.

Aged

Role of vagus nerve in increased DNA synthesis after hypothalamic ventromedial lesions in rat liver.

We recently reported that ventromedial hypothalamic (VMH) lesions produced an increase in DNA content in rat liver. In the present study, we examined the mechanism of increased hepatic DNA content produced by VMH lesions. Hepatic DNA content began to increase 3 days after VMH lesioning and continued to increase until 7 days after the lesioning. Hepatic DNA synthesis increased and reached maximum 3 days after the lesioning and then decreased to the initial level 7 days after lesioning. The increased DNA content and synthesis after VMH lesioning were completely inhibited by vagotomy (hepatic vagotomy or bilateral subdiaphragmatic vagotomy) and largely inhibited by the administration of atropine but not by administration of anti-insulin antibody. These results suggest that vagus firing produced by VMH lesions stimulates DNA synthesis in rat liver mainly through cholinergic receptor mechanisms.

Animals

Superoxide production by liver macrophages in a septic rat model--relation to arterial ketone body ratio.

The relationship between superoxide production by liver macrophages and arterial ketone body ratio (AKBR), which reflects the oxidation-reduction state in the mitochondrial compartment of hepatocytes, was studied in rats with lethal and sublethal septicemia induced by intravenous injection of live Escherichia coli 014. In the sublethal model, AKBR decreased transiently (p < 0.01) and superoxide production by isolated liver macrophages increased significantly after opsonized zymosan (OZ) stimulation (p < 0.05). On the other hand, in the lethal model, AKBR decreased markedly (p < 0.01) to below 0.4 without recovery, and superoxide production was not activated by OZ stimulation. Thus, when AKBR decreases to an irreversible level, below about 0.4, superoxide production by liver macrophages is impaired, while as long as AKBR remains reversible, more than about 0.4, it is enhanced. It is suggested that superoxide production by the Kupffer cells is related to the intrahepatic oxidation-reduction state in the septic model.

Alanine Transaminase