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T Kuroda

Publications and source records attributed to T Kuroda.

At least 19 recordsLinked to original sources
PubMed1995

Correlation between lipoprotein(a) and aortic valve sclerosis assessed by echocardiography (the JMS Cardiac Echo and Cohort Study).

An elevated serum level of lipoprotein(a) (Lp[a]) may be an independent risk factor for atherosclerotic disease, but the relation of Lp(a) to aortic valve (AV) sclerosis has not been determined. We measured serum concentrations of Lp(a) and investigated their relation to the presence of echocardiographic AV sclerosis in residents of a rural village in Japan. We measured serum Lp(a) levels in 347 men and 437 women aged 35 to 90 years (mean +/- SD: 62 +/- 11 years) who participated in mass screening examinations in Wara village, Gifu, Japan. AV sclerosis was assessed by long- and short-axis 2-dimensional echocardiographic views and continuous-wave Doppler echocardiography. AV sclerosis was graded as follows: 0 = normal AV; 1 = increased echo density; 2 = thickening or calcific deposits > or = 3 mm; and 3 = same as 2 with mildly restricted motion (pressure gradient < 16 mm Hg). Lp(a) levels ranged from < 1 mg/dl to 153 mg/dl. The 25th, 50th, and 75th percentile values were 7, 16, and 28 mg/dl, respectively. Lp(a) levels were significantly higher in women than in men (p < 0.01), and did not increase significantly with age. The prevalence of AV sclerosis (grades 2 and 3) increased significantly with age (p < 0.001). AV sclerosis was present in 65 (36.1%) of 180 subjects with Lp(a) levels > or = 30 mg/dl and in 77 (12.7%) of 604 subjects with Lp(a) levels < 30 mg/dl (p < 0.001). There were no significant differences in the prevalence of AV sclerosis in terms of sex, blood pressure, or levels of total cholesterol, high-density lipoprotein cholesterol, triglycerides, or blood sugar. We conclude that increased serum levels of Lp(a), as well as aging, are closely related to AV sclerosis.

Adult↗
PubMed1995

Subcellular localization of the APC protein: immunoelectron microscopic study of the association of the APC protein with catenin.

Mutations in the APC gene are linked to the development of sporadic colorectal tumors as well as to familial adenomatous polyposis. Recently, the APC protein was reported to associated with catenins, proteins that bind to the cell adhesion molecule E-cadherin. In the present study, we examined the distribution and localization of the APC protein and alpha -catenin in the normal mouse intestine by light and immunoelectron microscopy using specific antibodies. The APC protein was found to be localized in microvilli and in the apical and lateral cytoplasm of the epithelial cells, whereas alpha-catenin was detected only in the lateral cytoplasm. Double-labeling immunoelectron microscopy showed colocalization of the APC protein with alpha-catenin in the lateral cytoplasm, especially along the lateral plasma membrane, although a certain portion of the APC protein in this region was distributed independently of alpha-catenin. These results suggest that a portion of the APC protein localized in the lateral cytoplasm of intestinal epithelial cells functions in cooperation with catenins, whereas the APC protein in microvilli and in the apical cytoplasm has other functions independent of catenins.

Adenomatous Polyposis Coli Protein↗
PubMed1995

Preoperative intraperitoneal chemotherapy for gastric cancer, with special reference to delayed peritoneal complications.

Preoperative intraperitoneal (IP) chemotherapy was performed in 23 patients with gastric malignancies to inhibit peritoneal recurrence. Cis-diamminedichloroplatinum (CDDP) and mitomycin C (MMC) were administered intraperitoneally 3 days prior to surgery, at which time a very viscid peritoneum and mucinous intraperitoneal fluid were found in 100% and 83% of the patients, respectively. Inflammatory changes were microscopically observed in the subserosal layer of the resected stomachs and in the intraperitoneal fluid, but degenerative changes characteristic of cancer cells could not be seen. The 3-year survival rate of the stage III patients was 55.6%, and peritoneal recurrence was found in three of six patients with recurrence. Extensive adhesions were found in eight patients (34.8%) as a delayed peritoneal complication, and chronic bowel obstruction resulting from the adhesion developed in five patients (21.7%). Thus, we conclude that the administration of this IP chemotherapy demonstrated no definite antitumor effects or survival benefits, but was frequently associated with delayed peritoneal complications.

Adult↗
PubMed1995

Pericardiac metastasis from advanced gastric cancer.

A 64-year-old man complaining of anterior chest pain, weight loss, and neck tumors was found to have advanced gastric cancer with pleuritis carcinomatosa and multiple lymph node and bone metastases. The patient was treated with combination chemotherapy consisting of mitomycin C (MMC), tegafur (UFT), and lentinan, and then with MMC and 5-fluorouracil (5FU) instillation into the pleural spaces after pleural drainage. With these treatments, the primary tumors and cancerous ulcers of the stomach improved markedly, and the lymph node enlargement and pleural effusion disappeared completely. Afterwards pericardiac metastasis complicated by cardiac tamponade occurred, but repeated pericardiocentesis and administration of MMC into the pericardiac cavity effectively eliminated the effusion. These treatments appeared potentially useful for advanced gastric cancer with generalized metastases including pericardiac involvement. However, the patient died of cardiac tamponade with massive pericardiac bleeding, probably due to the repeated pericardiocentesis and/or the administration of anticancer drugs.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Significance of myeloperoxidase in rapidly progressive glomerulonephritis.

Antineutrophil cytoplasmic autoantibodies (ANCAs) are found in the sera of patients with systemic vasculitis and crescentic glomerulonephritis. We developed monoclonal antibodies against myeloperoxidase (MPO), which is a major perinuclear-ANCA antigen, and examined the presence of MPO in renal tissue from patients with rapidly progressive glomerulonephritis (RPGN) using these monoclonal antibodies. Myeloperoxidase was found in the glomeruli in four of five cases of perinuclear ANCA-positive RPGN, and the distribution pattern was different from that of immunoglobulin G. In perinuclear ANCA-negative crescentic glomerulonephritis, MPO also was detected in two of three cases. Myeloperoxidase was not detected in the capillary walls or mesangium in other nephropathies, such as minimal change disease, membranous nephropathy, and mesangial proliferative glomerulonephritis, or in normal controls. Myeloperoxidase activity was elevated and inversely correlated with the titer of MPO-ANCAs in the sera of perinuclear ANCA-associated RPGN. These data suggest that MPO plays an important role in the glomerular injury of RPGN.

Adult↗
PubMed1995

Transfer of copper and zinc from ionic and metallothionein-bound forms to Cu, Zn--superoxide dismutase.

Reactivity in transfer of copper (Cu) and zinc (Zn) to their binding sites of superoxide dismutase (SOD) was examined in vitro by the HPLC/atomic absorption spectrophotometry. Ionic Cu (cuprous and cupric ions) were incorporated more efficiently than the metal bound to metallothionein. Cu binds not only to the Cu-binding site but also to the Zn-binding site. Although Zn in the reaction medium and the metal bound to the Zn-binding site of SOD affected little the reactivity in binding of ionic Cu, they disturbed the reactivity of Cu bound to metallothionein to the Cu-binding site. Both ionic and metallothionein-bound Zn were transferred at a comparable efficiency to the Zn-binding site but not to the Cu-binding site. Co-existing ionic Cu but not metallothionein-bound Cu in the medium inhibited the binding of Zn to SOD. The results indicate that ionic Cu can be transferred to both Cu- and Zn-binding sites of SOD more efficiently than metallothionein-bound Cu, while both ionic and metallothionein-bound Zn are transferred only to Zn-binding site at a comparable efficiency.

Animals↗
PubMed1994

Effects of leukocyte and platelet depletion on ischemia--reperfusion injury to dog pancreas.

BACKGROUND/AIMS: Ischemia-reperfusion injury has been studied in various organs. Effects of leukocyte and platelet depletion on ischemia-reperfusion injury were evaluated using the isolated, perfused dog pancreas in vivo. METHODS: Pancreatic exocrine and endocrine functions were stimulated by an intra-arterial injection of cholecystokinin (10(-12) mol) and intravenous injection of glucose and arginine (1 g/kg body wt), respectively. The functions before and after 60 minutes of ischemia were evaluated in the no treatment and in the leukocyte and platelet depletion groups. RESULTS: Cholecystokinin increased prostaglandin I2 and thromboxane A2 production and stimulated exocrine pancreatic secretion. Glucose and arginine stimulated insulin and glucagon release from the pancreas. Sixty minutes of ischemia followed by 60 minutes of reperfusion damaged the pancreatic acinar and ductular cells. Ischemia of 60 minutes followed by 90 minutes of reperfusion damaged beta cells. Removal of leukocytes (97.6%) and platelets (99.4%) by using a filter throughout the experiment prevented the ischemia-reperfusion injury, reduced plasma lipid peroxide and thromboxane A2, and increased prostaglandin I2 levels. CONCLUSIONS: Leukocytes and platelets seem to damage the pancreas during ischemia-reperfusion by increasing the peroxidation of structurally important cell membrane lipids and reduced the thromboxane A2 prostaglandin I2 ratio, a predictor of cellular injury.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

The effect of a thromboxane A2 receptor antagonist (ONO 3708) on ischemia-reperfusion injury of the dog pancreas.

The effects of a thromboxane A2 receptor antagonist, ONO 3708, on ischemia-reperfusion injury of the pancreas were evaluated using an isolated in-vivo-perfused dog pancreas model. Pancreatic endocrine and exocrine function were stimulated with cholecystokinin octapeptide (10(-12) mol). This dose significantly increased endogenous prostaglandin I2 and thromboxane A2 production by the pancreas (both P < 0.001). A period of 60 min of ischemia and subsequent reperfusion induced an increase of pancreatic amylase release (P < 0.01) and a decrease of insulin release (P < 0.01). There was also a decrease of pancreatic juice and pancreatic bicarbonate and amylase output (au P < 0.01), suggesting damage to the acinar, ductular, and beta cells. Intravenous administration of ONO 3708 (200 micrograms/kg/min) throughout the experiment prevented these abnormalities of pancreatic secretion. It also reduced the plasma lipid peroxide level in the venous drainage (P < 0.01) and elevated the prostaglandin I2 level (P < 0.01) without changing thromboxane A2 levels. ONO 3708 thus appeared to protect the pancreas from ischemia-reperfusion injury by reducing the peroxidation of cell membrane lipids and by decreasing the thromboxane A2/prostaglandin I2 ratio, which is a predictor of cellular injury.

Amylases↗
PubMed1994

Delayed cerebral ischemia manifesting as peduncular hallucinosis after aneurysmal subarachnoid hemorrhage--three case reports.

Three cases of peduncular hallucinosis occurred in patients with aneurysmal subarachnoid hemorrhage. All patients underwent early clipping of the ruptured aneurysms of the anterior circulation. Several days after onset of subarachnoid hemorrhage, the patients complained of vivid visual hallucinations associated with abnormal sleep-waking rhythms, suggesting a diagnosis of peduncular hallucinosis. The hallucinations disappeared with administration of an increased dose of dobutamine. These findings indicated that peduncular hallucinosis might be a manifestation of delayed cerebral ischemia after subarachnoid hemorrhage. No other possible cause of neurological deficits such as hydrocephalus, cerebral infarcts, or metabolic encephalopathies was identified. Damage to the ascending reticular activating system has been implicated in the pathogenesis of peduncular hallucinosis. Cerebral vasospasm in the perforating arteries of the ascending reticular activating system was probably the cause of the hallucinosis in our patients.

Adult↗
PubMed1993

Effects of parathyroid hormone on pancreatic exocrine secretion.

The role of parathyroid hormone (PTH) and calcium on pancreatic exocrine secretion were observed using sham-operated and parathyroidectomized dogs. First, exocrine secretion of the pancreas stimulated with secretin and cholecystokinin octapeptide (CCK-8) was examined in vivo 3 weeks after parathyroidectomy. Secondly, perfusion experiments of isolated pancreas in the sham-operated and parathyroidectomized dogs were examined. In one experiment, volume of pancreatic juice and bicarbonate output, but not amylase output, was decreased in the parathyroidectomized dogs compared with those in the sham-operated dogs; no participation of calcium in exocrine secretion was revealed. In another experiment, high doses of PTH evoked increases of pancreatic juice and bicarbonate output without changing amylase output; as before, no participation of calcium in the exocrine secretion was observed. We conclude that (a) PTH increases volume of pancreatic juice and bicarbonate output, and (b) pancreatic exocrine secretion is modified by direct effect of PTH, and the pancreatic ductular cells, not the acinar cells, are the target for PTH.

Amylases↗
PubMed1992

New bronchodilators. 3. Imidazo[4,5-c][1,8]naphthyridin-4(5H)-ones.

In order to develop new oral bronchodilators, a series of novel imidazol[4,5-c][1,8]naphthyridin-4(5H)-ones 5 were designed and synthesized. Some of these new heterocycles exhibited more potent bronchodilator activity in vitro and in vivo than theophylline. With respect to modification at the 5-position, both phenyl and n-butyl substitution produced potent activity. Though bulk tolerance at N-3 is observed with short and small lipophilic groups, any substitution at the other positions and transformations of the parent skeleton eliminated activity. Thus 5-phenyl-1H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-one (23) (KF17625), which satisfied these conditions, was selected for further studies (antigen inhalation-induced bronchospasm model; minimum effective dose (MED) = 1 mg/kg, po; antigen-induced contraction of trachea (the Schultz-Dale reaction), IC50 = 2.2 microM). Compound 23 inhibited carbachol-, histamine-, or leukotriene D4-induced contraction and relaxed spontaneous tone in guinea pig isolated tracheal preparations with, 4- to 16-fold greater potency than aminophylline. Thus it appeared to relax directly the airway smooth muscle. 23 did not have any influence on adenosine binding at 10 microM, but inhibited canine tracheal phosphodiesterase (PDE) IV (IC50 = 12 microM) and concanavalin-A-induced histamine release from rat mast cells (44% inhibition at 10 microM). Although the detailed mechanisms of these compounds remain to be elucidated, this series of novel tricyclic heterocycles represents a new class of bronchodilator.

Animals↗
PubMed1992

New bronchodilators. 1. 1,5-Substituted 1H-imidazo[4,5-c]quinolin-4(5H)-ones.

A series of novel xanthine-based tricyclic heterocycles in 1H-imidazo[4,5-c]quinolin-4(5H)-ones was designed, synthesized, and tested as potential active bronchodilators. Inhibition of the Schulz-Dale (SD) reaction-induced contraction in trachea and inhibition of antigen inhalation-induced bronchospasm in passively sensitized guinea pigs served as primary in vitro and in vivo assays, respectively. Simultaneous measurement of acute lethal toxicity (minimum lethal dose; MLD, po) in mice allowed determination of a safety margin. The bronchodilatory activity of these heterocycles was considerably varied with the nature of substituents at the 5-position. The most active substituents at the 2- and 5-positions and on the aromatic ring were found to be hydrogen, n-butyl, and hydrogen, respectively. There was a bulk tolerance for lipophilic substituents at the 1-position. 5-Butyl-substituted compounds appeared to be less toxic than theophylline on the basis of MLD data. Thus 5-butyl-1-methyl-1H-imidazo[4,5-c]quinolin-4(5H)-one (10) (IC50 value of the SD assay = 0.25 microM, MLD > 300 mg/kg) was selected for further studies. Compound 10 (KF15570) reduced bronchoconstriction produced by antigen (Konzett-Rössler preparation in anesthetized guinea pigs, ED50 = 0.42 mg/kg, iv) more effectively than aminophylline (ethylenediamine salt of theophylline, ED50 = 7.8 mg/kg, iv) but had fewer side effects on the heart and CNS than theophylline. Compound 10 and its derivatives showed weak adenosine antagonism and phosphodiesterase (PDE) inhibition which could not account for their potent bronchodilation. Although their precise mechanism of action remains unclear, this series of novel tricyclic heterocycles represents a new class of bronchodilator.

Airway Resistance↗
PubMed1992

New antiinflammatory agents. 2. 5-Phenyl-3H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-ones: a new class of nonsteroidal antiinflammatory agents with potent activity like glucocorticoids.

We previously described new antiinflammatory agents, 4-hydroxy-2-oxo-1-phenyl-1H-1,8-naphthyridine-3-carboxamides 1. Further modification of the compounds bearing 1-phenyl-1,8-naphthyridin-2-one as a mother skeleton led to 5-phenylimidazo[4,5-c][1,8]naphthyridin-4(5H)-one derivatives 2 and 3. Regioselective synthesis of these compounds bearing a substituent at the 1- or 3-position was conducted according to the method shown in Schemes I and II. In this series of compounds, antiinflammatory activities were greatly influenced by the position and nature of substituents on imidazole. 3-Alkyl or 3-benzyl substitution result in the potent activity, but 1-substitution did not. Minor modification of the benzyl group reduced or eliminated the activity. Detailed examination of structure-activity relationships led to 3-benzyl-5-phenyl-3H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-one (22), which exhibited potent oral antiinflammatory activities in carrageenan-, zymosan-, and reversed passive Arthus reaction-induced rat paw edemas (ED40 = 5.3, 0.37 mg/kg, ED50 = 0.47 mg/kg, respectively). This broad activity of 22 was like that of glucocorticoids. Compound 22 did not affect activities of CO and 5-LO enzymes and receptor binding of various ligands. As one of the mechanisms of action, induction of release of glucocorticoids was postulated. These results suggest that 22 represents a novel class of antiinflammatory agents.

Animals↗
PubMed1992

A novel synthesis and potent antiinflammatory activity of 4-hydroxy-2(1H)-oxo-1-phenyl-1,8-naphthyridine-3-carboxamides.

New antiinflammatory agents 4-hydroxy-2(1H)-oxo-1-phenyl-1,8-naphthyridine-3- carboxamides 7 were designed and synthesized via a valuable intermediate, 1-phenyl-2H-pyrido[2,3-d][1,3]oxazine-2,4(1H)-dione (9). The nature of substituents on the amide nitrogen had a pronounced effect on antiinflamatory activity. Studies of structure-activity relationships led to compounds 33 and 34 bearing a pyridine ring on the amide nitrogen. Compounds 33 and 34 were active against carrageenin-, zymosan-, and arachidonic acid-induced rat paw edemas and also potently inhibited the reversed passive Arthus reaction in rats. Thus, they possess a broader spectrum of antiinflammatory activity than the classical nonsteroidal antiinflammatory drugs (NSAIDs) such as indomethacin and piroxicam.

Animals↗
PubMed1992

MRI demonstration of Kernohan's notch: case report.

We report a left acute subdural haematoma caused by rupture of a left anterior cerebral artery aneurysm, which progressed to left hemiparesis. Coronal MRI was superior to CT for visualizing Kernohan's notch.

Acute Disease↗
PubMed1992

Priming effects of leukotriene B4 on endothelial cell injury induced by TPA-activated leukocytes.

Among arachidonic acid metabolites, leukotriene B4 (LTB4) plays an important role in inflammation, such as in the activation, adhesion, chemotaxis, and invasion of leukocytes. In this paper, we examined the effect of LTB4 on endothelial cell injury induced by polymorphonuclear leukocytes (PMNLs). 51Cr release, a marker of cellular injury, was elicited from prelabeled endothelial cells when the cells were cocultured with PMNLs activated by phorbol ester (TPA, 12-O-tetradecanoyl-phorbol-13-acetate). Under this condition, pretreatment of PMNLs with LTB4 enhanced their injury in a dose-dependent manner (0.2-2 microM). However, LTB4 alone at any dose could not induce any cellular injury. We also determined the amount of active oxygen species produced by PMNLs in response to TPA. The intensity of luminol-dependent chemiluminescence, a marker of active oxygen production, in PMNLs was also increased by pretreatment with 1 microM LTB4. These data suggest that LTB4 enhances endothelial cell injury by the priming effect on active oxygen production in activated PMNLs.

Cell Adhesion↗
PubMed1992

In vivo and in vitro antitumor activity of mitomycin C conjugates at 7-N position through a linker containing thiocarbamate bond with CD10 monoclonal antibody.

Through a linker containing thiocarbomate bound to the 7-N position of mitomycin C (MMC), conjugates with a monoclonal antibody to CD10 (NL-1) were prepared, and their antitumor activities were examined. All five conjugates, except one, showed in vitro cytotoxicity to two CD10+ lymphoid cell lines superior to MMC. The conjugate displaying the highest cytotoxicity was selected and further tested against three CD10+ and two CD10- lymphoid cell lines in vitro. The conjugate with NL-1 antibody demonstrated higher cytotoxic activity against CD10+ tumor cells than the control conjugate with normal immunoglobulin, while there was no significant difference, when tested against CD10- tumors. The cytotoxic activity of the NL-1 conjugate to CD10+ tumors was significantly blocked by NL-1 antibody. In vivo antitumor activity of the NL-1 conjugate was then tested against a CD10+ tumor transplanted to nude mice, and side effects were recorded. The NL-1 conjugate (4 mg/kg) showed an in vivo antitumor effect similar to MMC (2 mg/kg), which is at nearly maximal tolerable dose; the latter induced decreases in numbers of leukocytes and platelets, while the former did not, suggesting less side effect by the NL-1 conjugate. Since MMC demonstrates a broad spectrum of antitumor activity, the conjugate, as such, may be applicable for the treatment of cancer patients.

Animals↗