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Biomedical subjects

M Tominaga

Publications and source records attributed to M Tominaga.

At least 163 records · Page 9Linked to original sources
PubMed1997

[A case of primary mediastinal choriocarcinoma].

A 27-year-old man with primary mediastinal choriocarcinoma was reported. He was admitted with complaint of right chest pain and dyspnea. Chest X-ray film and computed tomography of the chest revealed a bulky mass at anterior mediastinum and right pleural effusion. Physical examination revealed bilateral gynecomastia, and the serum beta-HCG level was cap at 500 ng/ml. The specimens obtained by percutaneous needle biopsy of the mediastinal mass showed cytotrophoblasts and syncytiotrophoblasts. He received 4 cycles of anti-cancer chemotherapy, and underwent resection for a residual mass, in which viable cancer cells remained in histological examination. In spite of additional chemotherapy, multiple lung metastasis developed rapidly. High dose chemotherapy, with carboplatine (200 mg/m2 x 4 days), etoposide (250 mg/m2 x 4 days) and cyclophosphamide (50 mg/kg x 2 days) was performed in combination with peripheral blood stem cell autotransplantation. However, brain metastasis set in and he died of respiratory failure 9 months after the onset of symptoms.

Adult↗
PubMed1997

[The effects of surfactant-TA on bleomycin-induced lung injury and lung fibroblast proliferation].

We investigated whether artificial surfactant modified pulmonary fibrosis following the intratracheal administration of bleomycin (BLM 3.75 mg/kg) in rats. Twenty-four hours after the administration of bleomycin, the lungs were washed twice with surfactant-TA (S-TA, 1 mg/ml, 6 ml x 2 times), and replaced with 0.5 ml of 10 mg/ml S-TA. Fourteen days later the animals were sacrificed and the lungs were assayed for collagen content and pathologic changes. BLM-treated rats showed both increases in wet lung weights and lung collagen content, and a loss in body weights (due to lung injury and fibrosis), but these changes were significantly inhibited by the intratracheal administration of S-TA. In vitro studies demonstrated that S-TA inhibited lung fibroblast proliferation in a dose dependent manner (0.01-0.5 mg/ml). This inhibition was also seen in native rat lung surfactant and its protein and lipid components. However, S-TA, did not change the number of rat type II pneumocutes in culture, and likely protected type II cells from dedifferentiation. S-TA inhibited BLM-induced pulmonary fibrosis, probably by directly inhibiting lung fibroblast proliferation.

Animals↗
PubMed1996

OPC-18790, a novel positive inotropic agent, has both arterial and venous vascular dilating actions in the dog.

OPC-18790, (+/-)6-[3-(3,4-dimethoxybenzylamino)-2- hydroxypropoxy]-2(1H)-quinolinone, is a novel positive inotropic agent with a moderate vasodilating action. We examined the vasodilating action of OPC-18790 in detail in the pentobarbital-anesthetized dogs using a colored microsphere technique for resistance vessels and a mean circulatory filling pressure method for capacitance vessels. Intravenously (i.v.) infused OPC-18790 increased the first derivative of left ventricular pressure (LVdP/dt max), cardiac output, heart rate and decreased total peripheral resistance but did not affect mean blood pressure. OPC-18790 significantly increased arterial blood flow distribution to heart and decreased vascular resistance in heart. OPC-18790 at 300 micrograms/kg i.v. and nitroglycerin at 50 micrograms/kg i.v. did not affect mean circulatory filling pressure in intact anesthetized dogs, but both compounds decreased mean circulatory filling pressure in spinally anesthetized dogs. OPC-18790 also decreased resistance to venous return but nitroglycerin did not. These results suggest that OPC-18790 has both arterial and venous vasodilating actions in addition to its positive inotropic action. These actions may produce an improvement of cardiohemodynamics in heart failure.

Animals↗
PubMed1996

Orally active, nonpeptide vasopressin V2 receptor antagonists: a novel series of 1-[4-(benzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepines and related compounds.

This paper describes a novel series of nonpeptide vasopressin V2 receptor antagonists. It has been demonstrated that the 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-benzazepines and 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-1,5-benzodiazepines show a high affinity for V2 (and V1a) receptors. Among the 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-benzazepine series, compounds with an alkylamino group on the benzazepine ring have been shown to have oral activity. A lipophilic group at the ortho position on the terminal benzoyl ring is important for both high V2 receptor affinity and oral activity. On the basis of these favorable properties, clinical testing of 31b has begun for use as an oral and iv aquaretic agent.

Administration, Oral↗
PubMed1996

Intracerebroventricular injection of methylatropine suppresses insulin response to oral glucose load in rats.

Hepatic glucoreceptor-vagal afferent inputs to the central nervous system and pancreatic vagal efferent stimuli are important for insulin secretion. In the present study, we examined the effect of intracerebroventricular (i.c.v.) injection of atropine methyl bromide (methylatropine) on the insulin response following glucose ingestion in rats. When rats were injected with methylatropine i.c.v., the plasma glucose concentration increased, the insulin response reduced, and glucagon-like peptide-1 (7-36) amide (tGLP-1) was unchanged following an oral glucose load, compared with the controls. The plasma insulin response following an intravenous glucose load was not affected by i.c.v. or intraperitoneal injection of methylatropine. A transient increase in plasma insulin after selective hepatic vagotomy was inhibited by i.c.v. injection of methylatropine. Arterial blood pressure or pulse rate was not changed by i.c.v. injection of methylatropine. These results show that the central nervous system plays an important role in the vagal control of the insulin response to glucose ingestion. In rats, for the insulin response soon after glucose ingestion (early phase insulin response), direct neural control (hepatic vagal afferent-central nervous system-pancreatic vagal efferent) of the islet B cells seems more important than the intestinal insulinotropic hormone, tGLP-1.

Administration, Oral↗
PubMed1996

Pharmacokinetics of intravenous adriamycin for anhepatic chemotherapy during liver transplantation.

Frequent recurrence of hepatocellular carcinoma after liver transplantation indicates the necessity to eliminate patients with advanced disease and combine transplantation with some form of perioperative adjuvant chemotherapy. This study was undertaken to elucidate adriamycin pharmacokinetics for anhepatic chemotherapy during liver transplantation. beagles of both sexes were allocated into two groups, controls (n = 4) and anhepatic animals with total hepatectomy under venovenous bypass (n = 5). In both groups, adriamycin was administered in 1 min at a dose of 1 mg/kg through the left antecubital vein and peripheral blood was obtained at intervals for up to 2 h to determine the plasma adriamycin levels. The animals were then sacrificed to determine tissue adriamycin levels in the liver, kidney, heart, lung, and skeletal muscle. Plasma adriamycin levels in anhepatic animals were significantly higher than those in controls at all measured time points after 10 min, resulting in a 50% reduction of the mean total body clearance of adriamycin compared with controls (P < 0.01). However, there was no statistically significant difference in adriamycin levels between the two groups for all measured tissues except for the liver. Despite the complete lack of hepatic function, anhepatic animals showed only a 50% reduction in total body clearance of adriamycin compared with normal controls, probably due to compensatory excretion from other organs such as the kidney. These results suggest that systemic chemotherapy with the standard dose of adriamycin may be tolerable during the anhepatic period of liver transplantation with enhanced tumoricidal effects on micrometastases.

Animals↗
PubMed1996

A novel paper cuff for vascular reconstruction in canine liver transplantation.

A new, simple method of producing optimal cuffs using thin paper and then setting it in resin for vascular reconstruction in canine liver transplantation is herein described. Thin Paper was cut into a paper tape strip. By fixing both ends of this paper tape, a cylinder paper core of any desired size could thus be obtained. The paper core was immersed into a two-liquid mixture-type resin, removed, and left to harden. The paper cuffs (0.2 mm or less in thickness) were then used for anastomoses of the portal vein and the infrahepatic inferior vena cava in a series of 10 consecutive canine liver transplantations. Out of 10 animals, 8 survived for more than 5 days. The vascular patency in these 8 animals at the cuff anastomotic sites was 100% at postmortem. We therefore conclude that this paper cuff appears to be useful for various types of experimental liver transplantations in large animals.

Anastomosis, Surgical↗
PubMed1996

Percutaneous hepatic venous isolation and extracorporeal charcoal hemoperfusion for high-dose intraarterial chemotherapy in patients with colorectal hepatic metastases.

The results of treating 12 consecutive patients with unresectable colorectal hepatic metastases with a hepatic arterial infusion of high-dose Adriamycin, 100-120 mg/m2, using hepatic venous isolation (HVI) and charcoal hemoperfusion (CHP) are reported herein. Adriamycin was administered over 5-15 min under extracorporeal drug elimination by HVI-CHP. HVI was percutaneously accomplished by either the double-balloon technique using a Fogarty occlusion catheter (8/22F) or a balloon-tipped catheter (16F). During the infusion, isolated hepatic venous blood was filtered by CHP and pumped into the left axillary vein. There were no lethal complications, and good hemodynamic tolerance to HVI-CHP was confirmed. Tumor liquefaction accompanied by a sharp decrease in serum carcinoembryonic antigen levels by more than 50% of pretreatment levels was observed in 6 of the 12 patients 1 month after treatment. Apart from chemical hepatitis, which developed in 11 (92%) of the patients, the Adriamycin toxicities were well controlled following the development of nausea and vomiting in 2 patients (17%), leukopenia < 2,000/mm3 in 3 (25%), and gastric ulcer in 1 (8%). These results indicate that this method is a safe and useful procedure for otherwise hazardous high-dose intra-arterial chemotherapy in patients with unresectable hepatic tumors.

Adult↗
PubMed1996

Centrifugal pump-assisted venous bypass between the superior mesenteric vein and the umbilical vein during portal vein resection.

We describe herein our method of performing centrifugal pump-assisted venous bypass between the superior mesenteric vein and the umbilical vein, developed with the aim of preventing congestion of the small intestine and promoting strong and constant hepatic blood flow during portal vein resection. By using this bypass method, portal vein resection and reconstruction was able to be carried out with ease and safety in six patients undergoing surgery for a pancreatic mass or cancer. No coagulation abnormalities, thrombocytopenia, leukocytopenia, severe liver dysfunction, or portal vein thrombosis developed in any of the patients postoperatively. Thus, we highly recommend this simple and reliable method of bypass when portal vein resection is being performed.

Carcinoma, Acinar Cell↗
PubMed1996

Effect of halothane and isoflurane on in situ diameter responses of small mesenteric veins to acute graded hypercapnia.

The purpose of the present study was to quantify the inhibitory effect of inhaled halothane and isoflurane on acute hypercapnia-induced responses of capacitance-regulating veins and related cardiovascular variables in response to sequential 40-s periods of 5%, 10%, 15%, and 20% inspired CO2 (FICO2). Measurements were made in normoxic alpha-chloralose-anesthetized rabbits before, during, and after either 0.75 minimum alveolar anesthetic concentration inhaled halothane or isoflurane. The graded hypercapnia caused graded venoconstriction and bradycardia but minimal pressor responses. Hypercapnia-induced venoconstriction was blocked by prior local superfusion of the exposed veins with 3 x 10(-6) M tetrodotoxin. Both the hypercapnia-induced venoconstriction and bradycardia responses were significantly attenuated by halothane or isoflurane and did not fully recover after removal of the anesthetics from the circulation. Both anesthetics produced a significant baseline (i.e., prehypercapnia) hypotension and a tendency toward a resultant tachycardia. The baseline hypotension did not recover completely after elimination of the anesthetic. Neither anesthetic altered baseline vein diameter. These results agree with previous studies demonstrating that hypercapnic acidosis produces mesenteric venoconstriction by elevating excitatory sympathetic efferent neural input via activation of peripheral and central chemoreceptors and that bradycardia results from activation of compensatory baroreflexes. The neural components of these reflexes are possible primary sites for attenuation of these cardiovascular responses by halothane and isoflurane.

Acute Disease↗
PubMed1996

Hereditary caeruloplasmin deficiency: clinicopathological study of a patient.

A 58 year old patient with dementia, oral dyskinesia, and diabetes mellitus is described. He had an undetectable concentration of serum caeruloplasmin, as an autosomal recessive trait. Brain MRI disclosed a pronounced hypointensity in the bilateral putamina, caudate, and dentate nuclei on both T1 and T2 weighted images. Pathological findings were mainly in those regions of the brain and consisted of neuronal cell loss with gliosis, heavy iron deposition, and spheroids. Visceral organs also had iron deposition, especially severe in the liver and pancreas. The present patient and other recorded cases constitute a clinicopathological entity of hereditary caeruloplasmin deficiency, different from Wilson's disease.

Brain↗
PubMed1996

Distribution of cAMP-activated chloride current and CFTR mRNA in the guinea pig heart.

Guinea pig ventricular myocytes exhibit a Cl(-)-selective current regulated by the cAMP-dependent pathway. We have investigated the distribution of cAMP-activated Cl- channel current density and cystic fibrosis transmembrane-conductance regulator (CFTR) mRNA in three regions of the guinea pig heart: the atrium, and the epicardium and endocardium of the free wall of the left ventricle. The regional differences in the Cl- current density were investigated in enzymatically isolated myocytes using the whole-cell patch-clamp technique. Forskolin (1 mumol/L) activated Cl(-)-selective currents in all ventricular myocytes and 21% of atrial myocytes examined. The conductance density, estimated as the outward chord conductance normalized to cell capacitance, was greatest in epicardial myocytes (79.8 +/- 8.4 pS/pF, n = 21) and significantly lower in endocardial (59.8 +/- 9.5 pS/pF, n = 22) and atrial (10.9 +/- 5.0 pS/pF, n = 38) myocytes. The regional differences in CFTR mRNA expression levels were investigated by competitive reverse-transcribed polymerase chain reaction. The regional distribution of the mRNA levels was similar to that of the Cl- conductance density, ie, highest in the epicardium (23230 +/- 1840 molecules/microgram total RNA, n = 3), significantly lower in endocardium (10610 +/- 780 molecules/microgram total RNA, n = 3), and lowest in atrium (1450 +/- 290 molecules/microgram total RNA, n = 3). The data indicate that regional differences in CFTR mRNA expression in the guinea pig heart are responsible, at least in part, for the regional differences in cAMP-activated Cl- current density.

Animals↗
PubMed1996

Synthesis and biological activities of optically active 6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-quinolinone (OPC-18790).

The enantiomers of 6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-quinolinon e (OPC-18790), a novel cardiotonic agent, were synthesized and evaluated for positive inotropic activity. The key intermediates, 2,3-epoxypropoxy derivatives, were obtained by the alkylation of 6-hydroxy-2(1H)-quinolinone with optically active epichlorohydrin and subsequent ring closure. In an in vitro study, the (R)-(+)-isomer was about 10-fold more potent than the (S)-(-)-isomer.

Animals↗
PubMed1996

Structure-activity relationships of non-peptide vasopressin V1a antagonists: 1-(1-multi-substituted benzoyl 4-piperidyl)-3,4-dihydro-2(1H)-quinolinones.

During our systematic studies on the arginine vasopressin receptor V1a-antagonistic activity of 1-(1-benzoyl substituted 4-piperidyl)-3,4-dihydro-2(1H)-quinolinones, we found a general substituent effect on the benzene ring. Hydrogen-bonding ability at the ortho position was especially important for enhancement of the affinity of multi-substituted analogs. Details of the syntheses and structure-activity relationships for this series are presented.

Animals↗
PubMed1996

Hyper-adrenocorticotropinemia in a patient with Addison's disease after treatment with corticosteroids.

A 40-year-old man with Addison's disease due to adrenal tuberculosis retained high levels of adrenocorticotropic hormone (ACTH) after conventional hydrocortisone replacement. Plasma ACTH levels were completely suppressed by usual replacement with hydrocortisone (20 mg at 8:00 and 10 mg at 21:00) but rebounded to abnormally high levels the following morning. Administration of 2 mg or 8 mg of dexamethasone suppressed ACTH and cortisol. Magnetic resonance imaging of the brain showed a low-intensity lesion of the pituitary gland. Pituitary hyperplasia or microadenoma with preserved regulation of ACTH was considered to be the cause of the high plasma ACTH levels. The combination of hydrocortisone and dexamethasone reduced plasma ACTH levels.

Addison Disease↗
PubMed1996

Positive inotropic and chronotropic effects of toborinone and its electrophysiological properties in the isolated hearts of rabbits and guinea-pigs.

The inotropic and chronotropic actions of toborinone ((+/-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxy-propoxy]-2(1H)-qu inolinone CAS 128667-95-8, OPC-18790) in the isolated right atrial and papillary muscles of rabbit and guinea-pig were examined and compared with those of milrinone (CAS 78415-72-2), a pure cyclic GMP-inhibited phosphodiesterase inhibitor. OPC-18790 (10(-7)-10(-4) mol/l) and milrinone (10(-3)-10(-4) mol/l) exerted concentration-dependent increases of contraction in both atrial and papillary muscles isolated from rabbits and guinea-pigs. In the isolated right atrium of rabbits and guinea-pigs, OPC-18790 showed limited increase in heart rate, while milrinone increased heart rate concentration-dependently. OPC-18790 (10(-6) and 10(-5) mol/l in guinea-pigs and 10(-7)-10(-4) mol/l in rabbits) prolonged the action potential duration in the isolated papillary muscles, while milrinone exerted no such change. In whole-cell voltage clamp experiments using isolated cardiac myocytes of guinea-pigs, OPC-18790(10(-5) mol/l) increased the L-type calcium current and inhibited outward potassium currents such as inward rectifying currents and delayed rectifier currents. OPC-18790 and milrinone (10(-6), 3 x 10(-5) mol/l) increased intracellular cyclic AMP levels with an increase in developed tension in isolated right ventricular muscles of guinea-pigs. From the above results, OPC-18790 was shown to be a positive inotropic agent with limited chronotropic effect and electrophysiologically properties different from those of milrinone. It was suggested that the prolongation of action potential duration, which is due to the inhibition of potassium currents, may be involved in OPC-18790's mechanism of positive inotropic action with limited chronotropic effect in addition to the inhibition of cyclic GMP-inhibited phosphodiesterase.

Action Potentials↗