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Biomedical subjects

H Takase

Publications and source records attributed to H Takase.

At least 73 records · Page 4Linked to original sources

[Specificity of plasma peroxidized low density lipoprotein in lung cancer].

Plasma was sampled from patients with lung cancer (LC: n = 38), patients with atherosclerotic disease (AS: n = 20), and healthy persons (H: n = 32). Lipid peroxide and lipid constituents of low density lipoprotein (LDL) were measured after sequential ultracentrifugation. Lipid peroxide levels in LDL were in the following order: LC > AS > H. Cholesteryl ester, triglycerides, free fatty acid, free cholesterol, and phospholipids were stained on plates of thin-layer chromatography of LDLs in healthy persons. However, spot X1 between triglycerides and free fatty acid was clearly colored on those of patients with atherosclerotic disease, and clear spot X2 between free fatty acid and free cholesterol, and a little spot X1 was stained on those of patients with lung cancer except for the lipid constituents mentioned above. No significant differences in lipid constituents were found among the patients with different histological types of lung cancer. Although lipid peroxide concentrations were significantly higher in the patients with lung cancer and artherosclerotic disease than in healthy persons, there were marked differences between patients with lung cancer and patients with artherosclelotic disease in the constituents of LDL lipid peroxide.

Adult↗

[Effect of chronic inhibition of nitric oxide synthesis on vascular structure: remodeling or growth?].

Nitric oxide is an important regulator of vascular tone, as evidenced by the marked increase in blood pressure produced by the inhibition of its synthesis. Furthermore, nitric oxide may be implicated in the modulation of vascular growth, although in vitro and in vivo studies have provided conflicting results. The aim of this study is to determine the effects of chronic nitric oxide synthase inhibition, with or without antihypertensive treatment, on the structure of the basilar artery in the rat. Rats were treated for 6 weeks with N omega-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day) alone or in combination with verapamil (100 mg/kg/day) or with trandolapril (1 mg/kg/day). Untreated rats served as controls. The structure of perfused and pressurized basilar arteries were analyzed in vitro using a video dimension analyzer. Chronic L-NAME treatment increased systolic arterial pressure (229 +/- 5 vs 147 +/- 3 for controls; p < 0.05) and the media to lumen ratio of the basilar artery (0.22 +/- 0.02 vs 0.15 +/- 0.01 for controls; p < 0.05). This structural alteration was mainly due to remodeling (remodeling index: 76%), but not to growth (growth index: 8%, NS). The concomitant administration of verapamil and trandolapril prevented the increase in blood pressure (154 +/- 6 and 146 +/- 5 mmHg, respectively) and the structural changes produced by L-NAME (Media/lumen ratio: 0.15 +/- 0.01 and 0.14 +/- 0.01 mmHg, respectively). In fact, a positive correlation was observed between the media to lumen ratio and the systolic arterial pressure (r = 0.6; p < 0.001). The effect of the two antihypertensive treatments, as well as the correlation between the wall to lumen ratio and the arterial pressure, suggest that the remodeling of the basilar artery depends mainly on the elevation of arterial pressure with little contribution of the L-arginine pathway. Furthermore, the very small and non significant increase in the cross-sectional area of the basilar arteries from L-NAME-treated rats (growth index of 8%), suggest that nitric oxide does not play an important role in the modulation of normal cerebral vascular growth in vivo.

Angiotensin-Converting Enzyme Inhibitors↗

Gastrointestinal invasion by herpes simplex virus type 1 inoculated cutaneously into the immunosuppressed mice.

The pathogenesis of infection in mice with herpes simplex virus type 1 (HSV-1) strain 7401H was studied. Mice immunosuppressed by intraperitoneal injection of cyclophosphamide were inoculated cutaneously into the flank with the virus and developed severe zosteriform skin lesions. All of them died within 2 weeks after the infection, while most of the normal mice survived the viral infection with healing of the lesions. In the gastrointestinal tract of the immunosuppressed mice, macroscopic abnormalities were frequently observed, and infectious viruses were detected on days 7 to 9. The viruses were also detectable in the dorsal root ganglia and the spinal cord of thoracolumbar area on days 5 to 7, and in the celiac plexus on day 7. However, no viruses were detected in the blood. Immunohistological examination of the gastrointestinal tract revealed that the viral antigens were localized in Auerbach's myenteric plexus. These results suggest that HSV-1 inoculated into the flank skin invaded the gastrointestinal tract via the nervous system, which gastrointestinal involvement might possibly have caused the death of the mice.

Animals↗

Regio- and stereoselective synthesis of carbocyclic 2',3'-dideoxy-3'-fluoro nucleosides as potential antiviral agents.

The synthesis and antiviral activity of racemic carbocyclic 2',3'-dideoxy-3'-fluoro nucleosides are reported. Carbocyclic 2',3'-dideoxy-3'-fluoro nucleosides were obtained from the 3-fluoro cyclopentane derivative 4, which was prepared by two methods. The SN2-displacement of the hydroxyl group of (+/-)-(1 beta, 2 alpha, 3 beta, 4 beta)-4-acetamido-2-fluoro-3-hydroxycyclopentylmethyl acetate (1) with Ph3P-I2 followed by tin hydride reduction afforded the 3-fluoroamino alcohol derivative 3. Alternatively, the protected fluoroamino alcohol 3 was prepared by regio- and stereoselective bromo-fluorination of cis-4 beta-acetamidocyclopent-2-enemethyl acetate (5) with hydrogen fluoride-pyridine/N-bromosuccinimide followed by tin hydride reduction to remove the bromine atom. Carbocyclic 2',3'-dideoxy-3'-fluoroguanosine (14) thus obtained was moderately active against herpes simplex virus in vitro.

Adenoviridae↗

Pharmacological profile of gastric mucosal protection by marmin and nobiletin from a traditional herbal medicine, Aurantii fructus immaturus.

We studied the effects of marmin and nobiletin on the experimental acute gastric lesions, gastric transmucosal potential difference (PD) and gastric motor activity in rats and the contractions of isolated guinea pig ileum. Oral administration of marmin and nobiletin inhibited both the appearance of ethanol-induced gastric hemorrhagic lesions dose-dependently in a dose range of 10-50 mg/kg, with ED50 values for marmin and nobiletin being 17.2 and 8.0 mg/kg, respectively. However, marmin and nobiletin had minimal effects on aspirin-induced gastric lesions at a dose of 50 mg/kg, respectively. Marmin and nobiletin had no significant influence on the basal PD. Intragastrical administration of marmin and nobiletin at a dose of 25 mg/kg significantly prevented the PD reduction induced by ethanol. Both marmin and nobiletin given intragastrically at 25 mg/kg significantly inhibited gastric motor activity measured as intraluminal pressure recordings. Marmin and nobiletin exhibited concentration-dependent relaxations of contractions induced by acetylcholine, transmural electrical stimulation and histamine in isolated guinea pig ileum, respectively. These findings suggest that the anti-ulcer effects of marmin and nobiletin are ascribed primarily to the maintenance of the mucosal barrier integrity and inhibition of gastric motor activity and secondarily due to the prevention of the effects of endogenous acetylcholine and histamine.

Acetylcholine↗

Development of atherosclerosis in alloxan diabetic rats.

Rats with alloxan-induced diabetes developed severe atherosclerotic lesions when they were maintained on a 0.25% cholesterol diet for one year. The atheromatous changes developed at the aortic arch, appeared as early as 3 months after the start of the experiment, and increased thereafter. The diabetic rats also developed atherosclerosis when they were fed standard rat chow, but the area of the atheromatous lesion was about one tenth of that in rats fed the high-cholesterol diet. Normal rats did not develop atherosclerosis even when fed the high-cholesterol diet for one year. The alloxan diabetic rats showed no increase in body weight, but developed serum glucose levels as high as 600-800 mg/dl as well as high serum cholesterol levels and lower serum HDL-cholesterol levels. The development of atherosclerosis in these rats was significantly related to an increase in the serum cholesterol/phospholipid ratio, the atherogenic index (TC-HDLC/HDLC), and the serum total cholesterol level, but was not related to the serum glucose, HDL-cholesterol, triglyceride, or lipid peroxide levels. These relationships were found as early as B-16 weeks after the start of the experiment. These data suggest that the serum cholesterol/phospholipid ratio, the atherogenic index, and the total cholesterol level are important risk factors for the development of atherosclerosis in rats with alloxan diabetes.

Animals↗

Changes in the endothelial cyclooxygenase pathway in resistance arteries of spontaneously hypertensive rats.

Vasodilator responses to adenosine and acetylcholine (ACh) were studied in ring preparations of mesenteric resistance arteries of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Adenosine (10(-7)-3 x 10(-4) M) caused relaxations in rings with endothelium. The relaxation was more pronounced in WKY than in SHR. Removal of the endothelium in WKY, but not in SHR, reduced the relaxation. In rings without endothelium, the relaxation was identical in the two strains. In WKY, the cyclooxygenase inhibitor meclofenamic acid attenuated the relaxation to adenosine in rings with endothelium but not in rings without endothelium. With meclofenamic acid, the relaxation was identical in WKY arteries with and without endothelium. ACh (10(-9)-10(-4) M) evoked endothelium-dependent relaxations in WKY. In contrast, in SHR the muscarinic agonist evoked contractions at higher concentrations (10(-6)-10(-4) M), whereas lower concentrations of ACh caused relaxations similar to those observed in WKY. The contraction in SHR was completely inhibited by meclofenamic acid, and with meclofenamic acid the relaxation to ACh was identical in WKY and SHR. Thus, adenosine evokes endothelium-dependent (through release of cyclooxygenase product) and endothelium-independent relaxations and ACh evokes endothelium-dependent relaxations in rat mesenteric resistance arteries. In SHR, the endothelium-dependent responses to the agonists are altered owing to the changes in the endothelial cyclooxygenase pathway.

Acetylcholine↗

[Pharmacological studies on antidiarrheal effects of a preparation containing berberine and geranii herba].

We studied the effects of a preparation containing Berberine and Geranii Herba (BGH) on different diarrheal models of mice and the contractions of isolated guinea pig intestinal smooth muscle, comparing these effects with those of a preparation containing creosote (CSG) and loperamide (LP). BGH, as well as CSG and LP, significantly inhibited the diarrhea induced by castor oil or BaCl2, but not the diarrhea induced by pilocarpine or serotonin. BGH inhibited ACh-, Ba(2+)- or electrical stimulation (ES)-induced contraction of the ileum or colon at concentrations from 10(-6) to 10(-4) g/ml. On the other hand, the inhibitory effect of CSG on the ES-induced contraction was about one hundred times stronger than that on ACh- or Ba(2+)-induced contraction. The order of the inhibitory potency of LP on contractions of the ileum in this test was ES > Ba2+ > ACh, and LP showed stronger inhibition against the contraction of the ileum than that of the colon. These results suggest that BGH exerts its antidiarrheal action by inhibiting intestinal movement, and the mechanism of action of BGH may differ from those of CSG or LP.

Animals↗

[Pharmacological studies on antidiarrheal effects of berberine and geranii herba].

We studied the effects of berberine and Geranii Herba extract (GH) on different diarrheal models of mice, on the contractions of the isolated guinea pig intestinal smooth muscle and on the peristalsis in the rat intestine, comparing these effects with those of atropine (ATR) and papaverine (PAP). 1) Berberine significantly inhibited both the diarrhea induced by castor oil and that induced by BaCl2 at doses higher than 25 mg/kg, p.o., but did not inhibit diarrhea induced by pilocarpine or serotonin even at 250 mg/kg, p.o. GH exhibited a significant inhibition of BaCl2 induced diarrhea. ATR prevented pilocarpine-induced diarrhea most strongly in diarrheal models. PAP significantly inhibited castor oil-, BaCl2- and pilocarpine-induced diarrhea, but not the serotonin-induced one. 2) Berberine inhibited ACh- or Ba(2+)-induced contractions of the ileum and colon at a concentration of about 10(-5) g/ml, and PAP did so at about 10(-6) g/ml, but GH (10(-3) g/ml) failed to inhibit them. ATR prevented the ACh-induced contraction of the ileum and colon at concentrations 1/1000 of those needed to prevent the Ba(2+)-induced one. On the other hand, berberine as well as PAP exhibited a noncompetitive inhibition of the contractile response induced by ACh, whereas ATR showed a competitive inhibition. 3) Berberine, GH, ATR and PAP showed significantly inhibited the spontaneous peristalsis in the intestine. These results suggest that berberine and GH have antidiarrheal action and that the mechanism of action of berberine may be somewhat differ from that of GH.

Acetylcholine↗

Epidural anaesthesia for insertion of a femoral neck prosthesis in a patient with phaeochromocytoma.

A hemiarthroplasty for femoral neck fracture was successfully performed under combined epidural anaesthesia and light general anaesthesia before phaeochromocytoma removal. Pre-operative therapy was managed with doxazosin, enalapril and diltiazem. Peri-operative management facilitated maintenance of stable haemodynamic conditions. Post-operative pain management was provided with continuous 1% lignocaine infusion via an epidural catheter. The phaeochromocytoma was finally removed uneventfully 7 weeks after hemiarthroplasty.

Adrenal Gland Neoplasms↗

Sequence-specific single-strand DNA-binding proteins that interact with the regulatory regions of wheat histone H3 and H4 genes.

We identified two novel DNA-binding proteins, ssDBP-1 and ssDBP-2, in wheat germ nuclear extract that interact with the proximal sequences of the promoter regions of the wheat histone H3 and H4 genes. Mobility shift and methylation interference assays have demonstrated that these factors specifically bind to the single-strand DNA which partially overlaps the hexamer and octamer cis-elements of the H3 promoter. Both proteins are distinguishable from HBP-1a and HBP-1b which specifically bind to the H3 hexamer sequence. These ssDNA-binding proteins are supposed to regulate the transcription of the wheat histone genes.

Base Sequence↗

Differential effects of ursodeoxycholic acid and ursocholic acid on the formation of biliary cholesterol crystals in mice.

The preventive effect of 3 alpha, 7 beta, 12 alpha-trihydroxy-5 beta-cholanoic acid (ursocholic acid) and ursodeoxycholic acid on the formation of biliary cholesterol crystals was studied in mice. Cholesterol crystals developed with 80% incidence after feeding for five weeks a lithogenic diet containing 0.5% cholesterol and 0.25% sodium cholate. When 0.25% ursocholic acid or ursodeoxycholic acid was added to the lithogenic diet, the incidence as well as the grade (severity) of the gallstones were reduced. Plasma and liver cholesterol levels were decreased by ursodeoxycholic acid but not by ursocholic acid. Gallbladder cholesterol and phospholipid levels were decreased by both bile acids. The biliary bile acid level was decreased by ursocholic acid but not by ursodeoxycholic acid. After feeding ursocholic acid, its level in the bile was about 25% and the levels of cholic acid and beta-muricholic acid decreased. Fecal sterol excretion was not changed by ursocholic acid, but was increased by ursodeoxycholic acid. After feeding ursocholic acid, fecal excretion of deoxycholic acid, cholic acid, and ursocholic acid increased. No differences were found between mice, with or without gallstones, in plasma and liver cholesterol levels, biliary phospholipid and bile acid levels, fecal sterol and bile acid levels, and biliary and fecal bile acid composition. The results suggest that the lower incidence of crystal formation after treatment with ursocholic acid is probably by a different mechanism than with ursodeoxycholic acid. In the mouse model, ursodeoxycholic acid exerts its effect at least partially, by decreasing cholesterol absorption. Ursocholic acid is well absorbed and excreted into bile and transformed into deoxycholic acid by the intestinal microflora in mice.

Animals↗

[The mechanism of the inhibitory effects of oren-gedoku-to (OGT) on gastric acid secretion in rats].

The effect of oren-gedoku-to (OGT) on gastric acid secretion was examined in the perfused stomach of anesthetized rats. OGT (10-100 mg/kg) given intraperitoneally dose-dependently inhibited the gastric acid secretion stimulated by intracerebroventricular DN-1417, an analogue of TRH, but failed to inhibit the acid secretion stimulated by intracerebroventricular baclofen, an analogue of GABA. The inhibitory effect of OGT on DN-1417-induced acid secretion was antagonized by haloperidol (0.3 and 1.0 mg/kg, i.p.), a dopamine-1/2 antagonist or sulpiride (100 mg/kg, i.p.), a dopamine-2 antagonist; and it was also reversed by yohimbine (0.3 mg/kg, i.p.), an alpha-2 adrenergic antagonist, and prazosin, an alpha-1 antagonist. These results suggest that the ability of OGT to reduce acid secretion is mediated via not only dopamine receptors but also alpha-2 adrenoceptors.

Adrenergic alpha-Antagonists↗

Roles of sulfhydryl compounds in the gastric mucosal protection of the herb drugs composing oren-gedoku-to (a traditional herbal medicine).

We investigated the involvement of sulfhydryl compounds in the cytoprotective effect of each component herb drug composing Oren-gedoku-to (OGT) against ethanol-induced gastric lesions and potential difference (PD) reduction in comparison with that of OGT in rats. Pretreatment with N-ethylmaleimide (NEM) significantly blocked the cytoprotective effects of OGT, Coptidis rhizoma and Phellodendri cortex, but did not block the cytoprotective effects of Gardeniae fructus and Scutellariae radix. The inhibitory effects of OGT, Coptidis rhizoma and Phellodendri cortex against the PD reduction disappeared in the presence of NEM or diethyldithiocarbamate (DDC), whereas NEM or DDC had little or no effect with Gardeniae fructus and Scutellariae radix. These results suggest that the gastric mucosal protection of Coptidis rhizoma and Phellodendri cortex may be ascribed to the reinforcement of mucosal barrier resistance through endogenous sulfhydryl compounds and DDC-sensitive compounds, but those of Gardeniae fructus and Scutellariae radix may be independent of NEM- or DDC-sensitive compounds.

Animals↗

Effect of vitamin C depletion on serum cholesterol and lipoprotein levels in ODS (od/od) rats unable to synthesize ascorbic acid.

The effect of ascorbic acid deficiency on serum and liver cholesterol, phospholipid and triglyceride levels, serum lipoprotein levels and serum lipoprotein cholesterol levels were examined in male rats with a hereditary defect in ascorbic acid synthesis (ODS rats). Male homozygotes (od/od) and male rats of their parent strain (+/+) were each divided into four treatment groups and were fed vitamin C-deficient or vitamin C-replete diets containing either 0 or 0.5% cholesterol. During the 3-wk feeding-period the ODS (od/od) rats fed the vitamin C-deficient diet gradually decreased food intake, resulting in a lower body weight than that of od/od rats given ascorbic acid. The serum cholesterol level was significantly higher in the vitamin C-deficient od/od rats fed the cholesterol diet, and it tended to be higher in those fed the control (0% cholesterol) diet, whereas the liver lipid levels remained unchanged relative to those in od/od rats fed the vitamin C-replete diet. The serum very low density lipoprotein and high density lipoprotein (HDL) cholesterol levels were lower in od/od rats fed the vitamin C-deficient diet without cholesterol, but intermediate density lipoprotein and low density lipoprotein cholesterol levels were markedly higher in the vitamin C-deficient od/od rats than in od/od rats given ascorbic acid, regardless of dietary cholesterol level. The ratio of HDL2 cholesterol to HDL3 cholesterol was also higher in the vitamin C-deficient od/od rats. The parent strain of the od/od rats (+/+) showed no change due to vitamin C deficiency. These results suggest that vitamin C deficiency delays low density lipoprotein metabolism and produces hypercholesterolemia in male od/od rats.

Animals↗

Dual effects of capsaicin on responses of the rabbit ear artery to field stimulation.

1. The effects of capsaicin (Cap) on contractions of ring segments of rabbit ear artery induced by field stimulation were studied. 2. At low concentrations (0.3-3 microM) Cap caused transient enhancement and at higher concentrations (above 3 microM) inhibition of stimulation-induced contractions, without affecting noradrenaline (NA)-induced contractions. 3. In the continuous presence of high concentrations of Cap, rebound facilitation was observed after inhibition, and at this stage, Cap elicited less inhibition of the response. 4. Repeated application of Cap at 60 min intervals irreversibly desensitized the artery to the inhibitory effect of Cap. 5. Functional removal of the endothelium enhanced the facilitatory effect of low concentrations of Cap and attenuated its inhibitory effect. 6. Pretreatment with indomethacin abolished the facilitatory effect of Cap and enhanced its inhibitory effect, indicating that prostaglandins are involved in the action of Cap. The effect of indomethacin was more marked in preparations from which the endothelium had been removed. 7. Desensitization to substance P (SP) or substance K (SK), did not affect either the inhibitory or the facilitatory effect of Cap. 8. These results suggest that the dual effects of Cap on stimulation-induced contractions of rabbit ear artery may arise from the release of multiple mediators that act prejunctionally to modulate NA release. The stimulant effect seems to be mediated by prostanoids, while the inhibitory effect seems to be caused by a substance(s) that is not SP or SK. The possibility that the mediator is calcitonin gene-related peptide requires further study.

Animals↗

Evidence for the involvement of cyclic GMP in adenosine-induced, age-dependent vasodilatation.

1. Adenosine-induced dilatation of rat aorta was present in aorta taken from 4 week-old rats, attenuated with increase in age of rats to 8 weeks, and was virtually absent in the aorta from 12 week-old rats. 2. Removal of the endothelium by mechanical rubbing attenuated adenosine-induced dilatation. 3. Haemoglobin and methylene blue partly reversed the adenosine-induced endothelium-dependent dilatation. 4. The order of potency of adenosine derivatives was 5'-(N-ethylcarboxamido)adenosine (NECA) greater than 2-phenylaminoadenosine (CV-1808) greater than 2-chloroadenosine greater than N6-([R]-[-]-phenylisopropyl)adenosine (R-PIA) greater than adenosine greater than N6-cyclohexyladenosine (CHA) greater than N6-([S]-[+]-phenylisopropyl)adenosine (S-PIA), indicating that adenosine receptors mediating the dilatation are of the A2 subtype. 5. [3H]-NECA bound to preparations of membranes from rats of 4 weeks old; it was displaced more effectively by NECA and the A2 ligand CV-1808 than by the A1 ligands CHA and S-PIA. ligands CHA and S-PIA. 6. The number but not affinity of specific binding sites for NECA decreased considerably with increase in age of rats to 8 weeks, and binding sites for [3H]-NECA were hardly detected in membrane preparations from rats of 20 weeks old. 7. Adenosine caused a marked increase in cyclic GMP production, but did not induce an increase in the cyclic AMP level. 8. This increase in cyclic GMP production induced by adenosine was abolished by methylene blue or 8-phenyltheophylline, or by removal of the endothelium. 9. The age-associated decrease in adenosine-induced dilatation was found to be associated with a reduction in the formation of cyclic GMP, but not of cyclic AMP. 10. These results suggest that adenosine causes dilatation via A2 receptors by inducing production of an endothelium-derived relaxing factor (EDRF), which in turn stimulates soluble guanylate cyclase, and so increases production of cyclic GMP. It is also suggested that the main reason for the age-associated decrease in adenosine-induced dilatation is a decrease in the number of A2-receptors or the ability of the endothelium to produce EDRF, leading to decreased production of cyclic GMP.

Adenosine↗

[Two cases of pulmonary alveolar proteinosis with increased CEA].

Two cases of pulmonary alveolar proteinosis (PAP) with increased CEA were reported. Case 1 was a 62-year-old male with suspected pulmonary fibrosis, who was transferred to our hospital. Laboratory findings on admission revealed 31.3 ng/ml of CEA. Because he had severe dyspnea, lung biopsy was not carried out. His condition gradually deteriorated and he died of respiratory failure. Autopsy revealed he had PAP and no malignancy. Case 2 was a 48 year-old male referred to our hospital because of dyspnea. Serum CEA was 52.8 ng/ml. Microscopic examination of a transbronchial lung biopsy showed PAP. The level of CEA in bronchoalveolar lavage fluid was 151 ng/ml. Unilateral whole lung lavage was performed twice. With the improvement of chest X-ray findings, serum levels of CEA fell to normal level. The molecular weight of CEA in bronchoalveolar lavage fluid was 180,000. Immunochemical staining of CEA in lung revealed nonspecific findings.

Carcinoembryonic Antigen↗