Biomedical subjects

H Minato

Publications and source records attributed to H Minato.

At least 55 records · Page 3Linked to original sources

PubMed1997

Post-treatment of transient focal cerebral ischemia in rats with the novel cerebrovascular-selective Ca2+ channel antagonist (+/-)-(E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]-oxepine-11-yl)-4-(3-pheny l-2-propenyl)-piperazine dimaleate.

The efficacy of post-ischemic treatment with AJ-3941 ((+/-)-(E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]-oxepine-11-yl )-4-(3-phenyl-2- propenyl)-piperazine dimaleate, CAS 143110-70-7), a cerebrovascular selective Ca2+ channel antagonist, on brain infarction induced by focal ischemia-reperfusion in rats was evaluated. Focal ischemia was induced by transient occlusion of middle cerebral artery (MCA) with a 3-0 nylon monofilament for 90 min. One day after MCA occlusion (MCAo), brain infarct size was determined by measuring 2,3,5-triphenyltetrazonium chloride-negative stained area of the serial brain sections. The development of cerebral infarction was observed in both regions of cortex and subcortex, such as striatum, caudatum, putamen, hippocampus and corpus callosum. Post-ischemic treatment with AJ-3941 (1 or 3 mg/kg p.o., 10 min and 3 h after the occlusion) significantly reduced the infarct size and volume in the ipsilateral hemisphere in a dose-dependent manner, compared to the solvent control. The reducing effect was observed mainly in the cortical region, and a significant reduction of the subcortical infarct volume was found at the higher dose (3 mg/kg). Post-ischemic treatment with the thromboxane A2 synthetase inhibitor, sodium ozagrel (150 micrograms/kg/min i.v. infusion, between 1 h and 24 h after the MCAo) did not reduce the infarct volume in the hemisphere after ischemia-reperfusion. AJ-3941 had only minimum effect on the elevation of body temperature during ischemia-reperfusion. These results indicate that post-ischemic treatment with AJ-3941 may ameliorate the brain injury after the transient focal cerebral ischemia, and they suggest that AJ-3941 has beneficial effects for treatment of ischemic cerebral damage, such as stroke.

Animals↗

PubMed1997

Alacepril, an angiotensin-converting enzyme inhibitor, prevents cerebral vasospasm in subarachnoid hemorrhage model in rats.

The effects of angiotensin-converting enzyme (ACE) inhibitors was investigated on the development of cerebral vasospasm and on the endothelium-dependent relaxation in the rat subarachnoid hemorrhage (SAH) model. Alacepril or enalapril was used as an ACE inhibitor with or without a thiol moiety in the structure. SAH rats or sham-operated rats were produced by the injection of homologous blood or artificial cerebrospinal fluid into the cisternal magna, respectively. In the SAH rat, cerebral vasospasm was observed at 24 h after blood injection. Acetylcholine (Ach)-induced relaxation in basilar arteries from SAH rats significantly decreased compared to that from sham-operated rats, although the relaxation induced by 3-morpholinosydnonimine, sodium nitroprusside or papaverine did not decrease. These results suggest that the endothelium cell function of basilar arteries in SAH rats is damaged. Alacepril prevented both the development of cerebral vasospasm and the suppression in the Ach-induced relaxation of basilar artery in SAH rats. However, enalapril did not prevent the suppression of Ach-induced relaxation in SAH rats, despite the tendency to prevent cerebral vasospasm. Therefore, it is suggested that the preventive effect of alacepril on cerebral vasospasm could be based on its protective effect on endothelium-dependent relaxation system.

Acetylcholine↗

PubMed1996

Prevention by the new Ca2+ channel antagonist, AJ-3941, of loss of endothelium-dependent relaxation after subarachnoid hemorrhage in rats.

AJ-3941 ((+/-)-(E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]-oxepine-11-yl ) -4-(3-phenyl-2-propenyl)-piperazine dimaleate; CAS No. 143110-70-7), a cerebrovascular-selective Ca2+ channel antagonist having anti-lipid peroxidative action, was reported to prevent cerebral vasospasm following subarachnoid hemorrhage in rats. The present study was undertaken to determine whether AJ-3941 protects the impairment of cerebroarterial endothelium-dependent relaxation which is concomitantly induced with cerebral vasospasm. Subarachnoid hemorrhage biphasically suppressed the response to acetylcholine in rat basilar artery, at 0.5 h (n = 4; P < 0.06) and 1 day (n = 5; P < 0.05) after subarachnoid hemorrhage. The reduction of the responses was correlated significantly to the degree of vasospasm determined angiographically. This reduction was accompanied by a 49% increase of arterial lipid peroxide contents. Endothelium-independent relaxation in subarachnoid hemorrhage rats was preserved in response to 3-morpholinosydnonimine, sodium nitroprusside and papaverine. AJ-3941 prevented (n = 6-8, P < 0.05) the suppression of the acetylcholine-induced response and the increase in lipid peroxide content in subarachnoid hemorrhage rats. These results suggest that AJ-3941 could exert its vasospasmolytic effect by preserving endothelial function through its anti-lipid peroxidative action, in addition to its inhibition of vasospasmogen-induced vasoconstriction related to intracellular Ca2+ mobilization.

Acetylcholine↗

PubMed1996

Cloning, nucleotide sequence and expression of the gene encoding the cellulose-binding protein 1 (CBP1) of Fibrobacter succinogenes S85.

The nucleotide sequence of the gene encoding the Fibrobacter succinogenes S85 cellulose-binding protein 1 (CBP1) has been determined. The gene encodes a protein of 1054 amino acids with a molecular mass of 118614. The deduced amino acid sequence of CBP1 showed an extensive similarity to the cellulose-binding domain of an endoglucanase (EGCCD) from Clostridium cellulolyticum and contained the reiterated regions. The cloned gene was inserted into an expression vector, pRSETA, and was expressed in E. coli as a fused protein with the peptide consisting of six consecutive histidine residues. The fused protein was detected by immunoblotting using antiserum against CBP1, and exhibited the cellulose-binding activities.

Amino Acid Sequence↗

PubMed1996

Structural organization of pRAM4, a cryptic plasmid from Prevotella ruminicola.

A total of 530 strains of rumen bacteria were screened for the presence of plasmid DNA. The percentage of plasmid-bearing strains was found to be the highest among the Bacteroides/ Prevotella group (9.9%), while it was less than 1% in the Butyrivibrio (0.2%) and Clostridium (0.6%) genera. A small cryptic plasmid pRAM4 from Prevotella ruminicola T31 was subcloned in Escherichia coli and completely sequenced. Two open reading frames, encoding potential polypeptides of M(r) 32,322 (ORF1) and 32,122 (ORF2) with limited sequence similarity to replication initiation and mobilization proteins, respectively, could be identified within the sequence. The region upstream from ORF1 had an AT-rich (75%) region followed by four 22-bp direct repeats, a structure characteristic of replication origins. The plasmid hybridized at high stringency with plasmids from Bacteroides/Prevotella and Butyrivibrio, and with pBR322, suggesting that at least regions of the plasmid are widespread.

Amino Acid Sequence↗

PubMed1996

Expression of blood group-related antigens in cholangiocarcinoma in relation to non-neoplastic bile ducts.

The abnormal expression of blood group related antigens has been reported in many malignant tumours; however, such expression in cholangiocarcinoma has not been examined systematically. The expression of blood group-related antigens (A, B, H, Lewis(a), Lewis(b), Lewis(x), Lewis(y), carbohydrate antigen 19-9 and carcinoembryonic antigen) was investigated immunohistochemically in 75 cases of cholangiocarcinoma (31 peripheral type and 44 hilar type). In non-neoplastic bile ducts, A, B, and H antigens were expressed in large bile ducts, while Lewis(a,b,y) and carbohydrate antigen 19-9 were variably expressed in both large and small bile ducts. Lewis(x) and carcinoembryonic antigen was not found in non-neoplastic bile ducts. In cholangiocarcinomas, A, B, and H, antigens were more frequent in the hilar type than in the peripheral type, although the difference was not significant. The expression of the blood-group related antigens, particularly A, Lewis(a,b,y), carcinoembryonic antigen, and carbohydrate antigen 19-9, was frequent in the tumour cells in well differentiated adenocarcinomas, while their immunoreactivity was less frequent in poorly differentiated adenocarcinomas. The superanuclear and luminal expression of these antigens in carcinoma cells was frequent in well differentiated adenocarcinomas, and the diffuse, cell membranous and stromal expression of these antigens was relatively frequent in poorly differentiated adenocarcinomas and adenosquamous carcinoma. The A, B, and H immunoreactivity of both non-neoplastic bile ducts and cholangiocarcinomas was consistent with the host blood group type. These findings suggest that both the expression and intracellular distribution of blood group-related antigens in cholangiocarcinoma are related to the differentiation of cholangiocarcinoma and, possibly, to the parent structure.

ABO Blood-Group System↗

PubMed1996

Protective effect of the novel cerebrovascular-selective calcium antagonist (+/-)-(E)-1-(3-fluoro-6, 11-dihydrodibenz[b,e]-oxepine-11-yl)-4-(3-phenyl-2-propenyl)-piperazine dimaleate on ischemic brain damage after permanent middle cerebral artery occlusion in rats.

In this study the effect of post-ischemic treatment of AJ-3941 ((+/-)-(E)-1-(3-fluoro-6,11-dihydrodibenz [b,e]-oxepine-11-yl)-4-(3-phenyl-2-propenyl)-piperazine dimaleate, CAS 143110-70-7) a cerebrovascular-selective calcium antagonist, on brain infarction and edema in a rat model of focal cerebral ischemia with permanent middle cerebral artery occlusion (MCAo) was evaluated. Brain infarct size was determined at 24 h after MCAo by measuring 2,3,5-triphenyltetrazolium chloride-negative stained area of the serial brain sections. Post-ischemic treatment of AJ-3941 (3 mg/kg p.o.), 10 min and 3 h after the insult, significantly reduced brain infarct size by 44-80%, compared to vehicle control. The reducing effect was observed both in the cortical and subcortical regions. Three days after MCAo, contents of water and Na+ in the ipsilateral hemisphere significantly increased comparing with those in control rats. Post-ischemic treatment with AJ-3941 (3 and 10 mg/kg twice daily p.o. for 2 days) markedly inhibited the increase in water content and suppressed the increase in Na+ content. In the contralateral hemisphere, these contents showed no significant differences between vehicle-treated group and either control (non-operated) or AJ-3941-treated group. AJ-3941 had only minimum effect on body temperature and physiological parameters, such as blood pressure, blood gases and glucose, even when the maximum dose used (10 mg/kg) was repeatedly administered. These results indicate that post-ischemic treatment with AJ-3941 may ameliorate the brain infarction and edema after permanent focal cerebral ischemia, and they also suggest that AJ-3941 has a beneficial effect in the treatment of ischemic cerebral damage.

Animals↗

PubMed1996

Effect of (+/-)-(E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]-oxepine-11 -yl)-4-(3-phenyl-2-propenyl)-piperazine dimaleate on cerebral vasospasm and impairment of cerebral circulation in subarachnoid hemorrhage model in rats.

A subarachnoid hemorrhage (SAH) model in rats was produced by the injection of homologous blood into the cisterna magna. Effects of AJ-3941 ((+/-)-(E)-1-(3-fluoro-6,11 -dihydrodibenz[b,e]-oxepine-11-yl)-4-(3-phenyl-2-propenyl)-p iperazine dimaleate, CAS 143110-70-7) on the development of cerebral vasospasm and the change of regional cerebral blood flow (rCBF) following SAH was investigated in this model. Cerebral vasospasm following SAH showed a biphasic pattern with an early phrase at 10 min and a late phrase on 1 day after blood injection. The physiological parameters (blood pressure, heart rate and blood gas contents) remained stable within the physiological range throughout the course of the experiment. AJ-3941 (0.01 mg/kg i.v. or 0.3 mg/kg p.o.) significantly prevented the development of late phase cerebral vasospasm. Cisternal injection of homologous blood significantly reduced rCBF immediately after the injection and the reduction lasted during the observation period (30 min). Reduction in rCBF after the injection of homologous blood was prevented by AJ-3941 (0.01 mg/kg i.v.). rCBF in AJ-3941-treated rats completely returned to the basal values after 30 min. The present suggest that AJ-3941 may be useful in the prevention of late spasm and in the improvement of cerebral circulation impaired with SAH.

Animals↗

PubMed1995

Expression of pancreatic trypsinogen/trypsin and cathepsin B in human cholangiocarcinomas and hepatocellular carcinomas.

We evaluated in situ expression of pancreatic trypsinogen (PT) and cathepsin B (CB) in 10 normal livers, 37 cholangiocarcinomas (CCs), and 36 hepatocellular carcinomas (HCCs). In normal livers, PT was expressed in intrahepatic large bile ducts, septal bile ducts, and peribiliary glands, and CB was present in hepatocytes and all epithelial cells of the intrahepatic biliary system. In CCs, PT was present in 26 (70%), of which 24 expressed PT both in CC cells and the CC stroma, and the remaining two showed PT only in CC cells. The ratio of PT-positive cases was high in well-differentiated CCs, moderate in moderately differentiated CCs, and low in poorly differentiated CCs. PT in the CC stroma was present in continuity with PT-positive CC cells, suggesting that PT was secreted from CC cells. The CC stroma positive for PT frequently showed destructive features. CB was present in 32 CCs (86%) and located in both CC cells and the CC stroma. All PT-positive CCs simultaneously expressed CB, suggesting a close association of PT and CB. In HCCs, in contrast, PT was not present in any cases. CB was present in 33 HCCs (92%) and located in both HCC cells and the HCC stroma. In positive specimens, PT immunoreactivity was finely granular in the cytoplasm, whereas CB immunoreactivity was diffuse in the entire cytoplasm. These data suggest that after malignant transformation CCs and HCCs continue to express PT and CB, and CB, respectively. It seems possible that PT secreted from CC cells is converted into trypsin by CB, and that trypsin and CB play a role in CC invasion by degrading extracellular matrix proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

Thymic carcinoma involving the thyroid gland: report of two cases.

Two new cases of thymic carcinoma involving the thyroid gland and manifesting as thyroid tumors are presented. One tumor occurred within the thyroid gland and the other totally involved the thyroid gland. Microscopically they showed lobular architecture separated by fibrous bands and consisted of solid islands of squamoid to spindled epithelial cells with whorl formation resembling Hassall's corpuscle and variable amounts of lymphocytes. The squamoid to spindled epithelial cells were positive for cytokeratin but negative for thyroglobulin and calcitonin and the majority of lymphocytes showed a T-cell phenotype. One of the two cases had been diagnosed initially as squamous cell carcinoma of the thyroid. This type of thyroid carcinoma is relatively rare, but it should be differentiated from other types of thyroid carcinomas, especially squamous cell carcinoma, medullary carcinoma, or anaplastic carcinoma of the thyroid.

Aged↗

PubMed1995

Pylorus-preserving gastrectomy with radical lymph node dissection based on anatomical variations of the infrapyloric artery.

We devised a method for performing pylorus-preserving gastrectomy (PPG) with radical lymph node dissection without compromising pyloric blood flow, based on vascular anatomical evaluation of 210 celiac angiograms. The origin of the infrapyloric artery was variable, but consistently supplied blood flow to the pylorus and the posterior wall of the antrum. When the infrapyloric artery originated from the gastroduodenal artery or from one of its pancreatic branches (type A, 88%), the right gastroepiploic artery was divided at its origin, allowing the excision of all adjacent lymph nodes. When the infrapyloric artery originated from the right gastroepiploic artery (type B, 12%), the right gastroepiploic artery was divided distal to the infrapyloric artery origin and the short right gastroepiploic artery remnant was skeletonized of lymph nodes. We have used this technique to perform PPG on 25 patients with early gastric cancer in the middle third of the stomach with minimal morbidity and no mortality.

Adult↗

PubMed1995

Modulation of extraluminally induced vasoconstrictions by endothelium-derived nitric oxide in the canine basilar artery.

The present study was undertaken to investigate the role of endothelium in extraluminally induced vasospasm of the cerebral artery using isolated perfused canine basilar arteries. The extraluminal applications of high K+ and prostaglandin F2 alpha (PGF2 alpha) induced concentration-dependent vasoconstriction. Both constrictive responses were significantly enhanced by denuding endothelium. Additionally, the responses in the endothelium-intact arteries were markedly augmented by intraluminal perfusion with NG-monomethyl-L-arginine (L-NMMA). These results suggest that the inhibition of nitric oxide (NO) synthase in endothelium enhances increase in transmembrane Ca(2+)-influx which is a common constrictive mechanism to the vasoconstrictors. The augmentative action induced by L-NMMA was inhibited by intraluminal perfusion of L-arginine, but not by D-arginine. Furthermore, the augmentation was not observed in the arteries without endothelium. These results suggest that the endothelium may have a great significance on responsiveness to extraluminal vasoactive substances and that endothelium-derived NO may modulate the extraluminally induced vasoconstriction which is responsible for cerebral vasospasm after subarachnoid hemorrhage.

Amino Acid Oxidoreductases↗

PubMed1995

Papillary carcinoma of the thyroid gland with fibromatosis-like stroma: a case report and review of the literature.

A new case of a rare variant of papillary carcinoma of the thyroid gland with fibromatosis-like stroma is reported. The patient was a 43-yr-old woman who had a well demarcated tumor that showed an expansive growth from the left thyroid lobe into perithyroidal soft tissues. Histologically, the tumor was composed predominantly of a fibromatosis-like stroma in which were diffusely dispersed small follicles of papillary carcinoma. At the advancing front of extrathyroidal extension of the tumor, fibromyxomatous changes of soft tissues were preceded by infiltration of the papillary carcinoma component. Immunohistochemistry and electron microscopy showed that the stromal cells had a myofibroblastic nature. One metastatically involved lymph node did not show fibromatosis-like stroma. The patient has remained well with no evidence of recurrence for 1 yr.

Adult↗

PubMed1995

[The effect of the external biliary diversion on cobalamin functions].

We studied the effect of the external biliary diversion on cobalamin functions clinically and experimentally. Serum cobalamin was rising to 10 ng/ml or more in each patient with obstructive jaundice and the diverted bile contained high concentrations of cobalamin (10-80 ng/ml). A total volume of diverted cobalamin reached to 2-12 micrograms/day after the relief of obstruction and was maintained 2-8 micrograms/day even after 30 days. In experimental dogs, serum cobalamin decreased to 360 +/- 40pg/ml (about 31% decreases) subsequent eight weeks after the relief. The cobalamin concentration of liver decreased to 184 +/- 123ng/g (19% decreases) after four weeks and to 164 +/- 108ng/g (30% decreases) after eight weeks. The concentration of the different cobalamins in the liver showed that the proportion of dimethyl benzimidazolyl cobamide coenzyme (DBCC) decreased and the proportion of methylcobalamin increased. It is concluded that cobalamin (10 micrograms/day at least) should be administered when the diversion continues for a long term.

Aged↗

PubMed1994

[Survival of patients with gastric cancer treated with intra-lymph nodal injection of activated carbon particles absorbed mitomycin C].

We studied the efficacy of the intra-lymph nodal injection of the activated carbon particle absorbed mitomycin C (MMC-CH40) for gastric cancer. Ninety-five patients with gastric cancer underwent gastrectomy with D1 or D2 lymph node dissection. Of these, 38 patients were treated with intra-lymph nodal injection of MMC-CH 40 (MMC-CH 40 group). The other 57 patients were classified into the control group. The survival of MMC-CH group was significantly higher than that of the control group using generalized Wilcoxon method. However, since the percentage of stage IV was higher in the control group than in MMC-CH 40 group, the survivals of subgroups of stage I-III were compared. Although the percentage of the early gastric cancer was higher in the control group of stage I-III (n = 35) than in the MMC-CH group of stage I-III (n = 38), the survival curves of MMC-CH group were higher than in the control group. The difference in survival between the two groups was significant at 8 months after surgery. These results indicate that this new therapy improves survival in patients with stage I-III gastric cancer.

Absorption↗

PubMed1993

Inhibitory effect of the new calcium antagonist AJ-2615 on progression of atherosclerosis in cholesterol-fed rabbits.

The effects of a new calcium antagonist, AJ-2615, on progression of atherosclerosis were investigated in rabbits fed a diet high in cholesterol and compared with those of prazosin, diltiazem, and their combination. In the AJ-2615 (30 mg/kg p.o. once daily) group, high cholesterol diet-induced increases in plasma concentrations of total cholesterol, free cholesterol, and phospholipid were significantly decreased. In addition, increases in aortic lipids and calcium content, as well as those in the atherosclerotic lesion area were clearly reduced by AJ-2615. On the other hand, prazosin (3 mg/kg p.o. twice daily) and diltiazem (50 mg/kg p.o. twice daily) groups displayed no such inhibitory effects. However, the group receiving the combination of prazosin and diltiazem at their respective dose levels exhibited a significant reduction in the increase in calcium content of the aorta and a slight decrease in the atherosclerotic lesion area, although there was no decrease in plasma or aortic lipid content. These results suggest that in addition to its calcium antagonistic and alpha 1-adrenoceptor blocking actions, some other yet-unidentified properties of AJ-2615 might contribute to the antiatherosclerotic effect of this agent.

Animals↗

PubMed1993

Antihypertensive effects of AJ-2615, a new calcium antagonist with alpha 1-adrenergic blocking activity in experimental hypertensive animals.

The antihypertensive effect of AJ-2615 [(+/-)-N-(6,11-dihydrodibenzo[b,e]thiepin-11-yl)-4-(4-fluoro phenyl)-1- piperazinebutanamide maleate], a novel calcium (Ca) antagonist having alpha 1-adrenergic blocking activity as well, was compared with that of the existing Ca antagonists (diltiazem, nifedipine, and nicardipine) in various hypertensive models of dogs and rats. When given orally to renal hypertensive dogs (RHDs) and spontaneously hypertensive rats (SHRs), AJ-2615 (RHDs, ED25 mm Hg = 6.0 mg/kg; SHRs, ED25 mm Hg = 24.9 mg/kg) was approximately as effective as diltiazem (RHDs, ED25 mm Hg = 6.3 mg/kg; SHRs, ED25 mm Hg = 54.7 mg/kg) in lowering the blood pressure. This antihypertensive effect was slower in onset and longer in duration (RHDs, > or = 9 h; SHRs, > or = 20 h) compared with any of the other reference drugs. AJ-2615 (10 mg/kg p.o.) given to RHDs once daily for 29 days significantly reduced the blood pressure measured 24 h after each dose and caused a stable antihypertensive effect without major diurnal variations. When given in single oral doses to RHDs and SHRs, AJ-2615 had no large effect on the heart rate while the reference drugs induced a large increase or decrease in heart rate in response to a blood pressure fall. These results suggested that AJ-2615 has potential as a long-acting (once daily dosage regimen) antihypertensive drug without causing a steep blood pressure fall and tachycardia.

Adrenergic alpha-Antagonists↗

PubMed1993

Cell kinetic and morphological studies of human cholangiocellular carcinoma.

We investigated the cell kinetics and morphologies of cholangiocellular carcinoma (CCC) using 48 autopsied or surgically resected cases (47 were adenocarcinoma and the remaining adenosquamous cell carcinoma), all of which were formalin-fixed and paraffin-embedded. Cell kinetics were analyzed by counting the number of argyrophilic nucleolar organizer regions (AgNOR) using immunostaining of proliferating cell nuclear antigens (PCNA) and flow cytometric DNA analysis. Dedifferentiation of CCC was positively correlated with AgNOR number (2.22 +/- 0.21 in well differentiated, 3.66 +/- 0.85 in moderately differentiated and 4.17 +/- 0.49 in poorly differentiated adenocarcinomas, respectively). In 22 cases, the labeling index (LI) of PCNA was higher in moderately and poorly differentiated adenocarcinomas (24.0 +/- 2.35 and 26.0 +/- 4.89, respectively) than in well differentiated ones (10.8 +/- 2.14). A majority of well differentiated ones were diploid, while aneuploidy prevailed in moderately to poorly differentiated ones. These data suggest that cell proliferative indices and nuclear DNA analysis of CCC accurately reflect their histological grading. The anatomical location of CCC along the biliary tree had no relation to either of the cell kinetic data. In autopsy cases, the patients with organ and lymph node metastases tended to show a higher DNA index and aneuploidy. This study implies that a combination of several cell kinetic data is valuable for the evaluation of the biological behaviors of CCC, and also supports further studies of cell kinetics of CCC using small-sized biopsy specimens, as a prognostic indicator.

Adenoma, Bile Duct↗