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Biomedical subjects

M Gotoh

Publications and source records attributed to M Gotoh.

At least 451 records · Page 25Linked to original sources

Contra-IL 2; a suppressor lymphokine that inhibits IL 2 activity.

Suppressive activity of culture supernatant of AS-9 (AS-9 CS), a T cell hybridoma line that was derived from fusion of BW5147 thymoma and splenic T cells of anti-lymphocyte serum-treated C3H mice, was analyzed. AS-9 CS inhibited allogeneic cytotoxic T lymphocyte (CTL) generation as well as T cell proliferation to alloantigens and mitogens, but failed to inhibit B cell response to lipopolysaccharide or growth of tumor and fibroblast cells. Although addition of AS-9 CS to the allogeneic sensitization culture as late as on day 2 of incubation resulted in maximal inhibiton of CTL generation, removal of AS-9 CS on day 3 of incubation abolished its inhibitory effect. Addition of purified IL 2 together with AS-9 CS to the allogeneic sensitization cultures only partially abrogated the suppression. Experiments with IL 2-dependent cytotoxic T cell line (CTLL) showed that AS-9 CS suppressed the IL 2-induced proliferation of CTLL. Preincubation of AS-9 CS with CTLL removed its inhibitory effect on CTL generation. These results indicate that AS-9 CS interferes with the mechanism of T cell activation by IL 2. On this basis, AS-9 CS was named contra-IL 2.

Animals↗

Relationship between chlordane and its metabolites in blood of pest control operators and spraying conditions.

Chlordane has been widely used to protect soil and house foundations against termite infestation. Pest control operators (PCOs) are occupationally exposed to chlordane. The relationship between chlordane and its metabolites in blood of PCOs and spraying conditions were investigated. Chlordane and its metabolites were detected in the blood of some chlordane-exposed PCOs, but not in that of the controls. Trans-nonachlor and the metabolites oxychlordane and heptachlor epoxide were detected in the blood of PCOs. Total concentration of chlordane and its metabolites in blood (trans-nonachlor + oxychlordane + heptachlor epoxide) was less than 5.6 ppb (mean: 0.89 ppb). The concentration of chlordane and its metabolites in blood of chlordane-exposed PCOs was significantly correlated with the number of spraying days and the amount of chlordane sprayed, particularly with a large correlation coefficient (r = 0.81, P less than 0.001) with the spraying days in the three months prior to the medical examination. The concentration of chlordane and its metabolites in blood is considered to be a useful indicator of biological monitoring for chlordane exposed workers (PCOs).

Adult↗

The mode of action of prostaglandin E2, F2 alpha and prostacyclin on vesicourethral smooth muscle.

Interactions of prostaglandin E2 (PGE2), F2 alpha (PGF2 alpha) and prostacyclin (PGI2) with Ca2+ on the isometric contraction of rabbit detrusor muscle strips were studied using two types of Ca2+ antagonists of different mechanisms of action: verapamil and sodium nitroprusside (NP). The effects of PGI2 on vesicourethral smooth muscle and their relationship with cholinergic, adrenergic receptors and nervous activity were also investigated. PGE2 and F2 alpha (3 X 10(-8) to 3 X 10(-5) M) caused dose-dependent contraction of the strips. Pretreatment of the strips with verapamil (10(-7) to 10(-5)M) significantly inhibited PGs-induced contraction in a dose-dependent manner, whereas NP(10(-7) to 10(-5)M) failed to suppress the contraction. Relaxation of the preparations once contracted by PGE2 and F2 alpha (3 X 10(-6)M) was induced completely by addition of verapamil (10(-5)M), and incompletely by NP(10(-5) to 10(-3)M). Washing of the strips with Ca2+-free solution containing 0.01 mM EGTA completely eliminated spontaneous activity and diminished basal tension, but replenishment of Ca2+ (0.5 to 10 mM) to the medium caused dose-related contraction and spontaneous activity of the strips. Addition of PGE2 and F2 alpha to the Ca2+-free medium enhanced Ca2+-induced contraction and spontaneous activity during Ca2+ replenishment, which were significantly inhibited by pretreatment with verapamil (10(-7) to 10(-5)M) in a dose-dependent manner, but not affected by NP (10(-7) to 10(-5)M). In Ca2+-free medium containing 0.1 mM EGTA, PGE2 and F2 alpha caused a slight degree of tension increase of the strips dose-dependently at the higher concentration exceeding 3 X 10(-6)M. PGI2 (10(-9) to 3 X 10(-4)M) caused dose-dependent contraction of the strips from the bladder body, base and the urethra. The contractile action of PGI2 was greatest on the bladder body, less on the base and minimal on the urethra. The effect of PGI2 was less potent than those of PGE2 and F2 alpha. The PGI2-induced contraction was slow in onset, short lasting, and not affected by pretreatment with phentolamine, propranolol, atropine, hexamethonium, hemicholinium-3 and tetrodotoxin. The interactions of PGI2 with Ca2+ were similar to those of PGE2 and F2 alpha.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Intravesical instillation of a calcium entry blocker and its effects on detrusor contractility: in vitro and vivo experiments.

The effects of intravesical instillation of a Ca2+ entry blocker (verapamil) on the contractility of the bladder detrusor muscle of the rabbit were investigated in vitro and in vivo. In in vitro experiments, using whole bladder preparations, spontaneous contractile activity and contraction induced by direct electric stimulation or acetylcholine were monitored. Both activities were inhibited in a time-dependent manner after the intravesical instillation of 7.5 mg. verapamil. The amplitude of spontaneous contraction 90 minutes after the instillation, was reduced to 10 per cent of control (before the instillation), and the response to electric stimulation and acetylcholine were inhibited to 16 per cent and 38 per cent of controls respectively. The detrusor contractility was still inhibited two hours after the removal of verapamil from the bladder. This inhibition of the detrusor contractility after removal of verapamil was completely reversed by adding four mM Ca2+ intravesically. During in vivo experiments, the changes of intravesical pressure elicited by pelvic nerve stimulation and the systemic arterial pressure were monitored. Sixty minutes after the intravesical instillation of 10 mg. verapamil, the rise of the intravesical pressure following the pelvic nerve stimulation was inhibited to 18 per cent of control, while the systemic arterial pressure was not affected. It is suggested that the intravesical instillation of verapamil can inhibit detrusor contractility without affecting cardiovascular status.

Acetylcholine↗

Role of calcium ion antagonists of the bladder detrusor muscle: in vitro and in vivo study.

Calcium (Ca2+) ions play an important role in the contractility of the detrusor. Most of the neurotransmitters and modulators act on the detrusor through altering the final intracellular concentration of Ca2+. We studied three commonly used Ca2+ antagonists on their effect of detrusor contractility in vitro: verapamil, nifedipine and segontin. All three inhibited the detrusor-induced contraction in a dose-dependent fashion. Verapamil showed noncompetitive inhibition. Segontin showed a competitive inhibition on both phasic and tonic contractions of the detrusor strips. Nifedipine selectively inhibited the phasic contraction noncompetitively but competitively suppressed the tonic contraction. The in vivo application of verapamil on the bladder of rabbits with multiple-sclerosis-like disease showed a significant increase in bladder capacity. The study shows the possibility of the potential use of Ca2+-antagonist to suppress the problem of bladder instability.

Animals↗

Effects of liver-tumor promoters on phalloidin sensitivity of rat hepatocytes.

Hepatocytes were isolated by a collagenase perfusion method from male F-344 rats fed a diet containing 0.05% phenobarbital (PB), 0.05% dichlorophenyltrichloroethane (DDT), 0.25% ethyl-alpha-p-chlorophenoxyisobutyrate (CPIB), 0.02% methapyrilene hydrochloride (MP), 0.05% amobarbital (AB) or 0.05% diphenylhydantoin (DPH) for 8 weeks. An increase in the incidence of gamma-glutamyltransferase (GGT)-positive hepatocytes was found in rats fed PB or DDT, while CPIB strikingly decreased the incidence. There was no change in the incidence in rats fed MP, AB or DPH. Sensitivity to phalloidin, in terms of formation of multiple cytoplasmic blebs, of the 1-h cultured hepatocytes of rats fed PB, DDT or MP was decreased in both GGT-negative and GGT-positive hepatocytes. The sensitivity of GGT-negative hepatocytes of rats fed CPIB was also decreased. Experiments on phalloidin consumption showed decreases in the hepatocyte toxin uptake of rats fed PB, DDT, CPIB or MP. AB and DPH had no effects on the sensitivity of both GGT-negative and GGT-positive hepatocytes.

Animals↗

Immunological characteristics of purified pancreatic islet grafts.

In a DBA/2 (H-2d) pancreatic islet-to-B6AF1 (H-2b/k.d) recipient combination, the graft survival of hand-picked islets was compared with that of "crude digested" islets that were prepared simply by collagenase digestion and Ficoll gradient separation and were contaminated with lymph nodes and vascular and ductal tissue. Islet allografts were transplanted into the renal subcapsular space of streptozotocin-induced diabetic recipients. No immunosuppression was used. All the crude digested islet allografts were acutely rejected between days 7 and 18 with a median survival time (MST) of 10.2 +/- 2.5 days. In contrast, 33% (3/9) of the purified islet allografts survived more than 100 days. Simultaneous transplantation of purified islets and contaminating tissue resulted in a shorter graft survival (MST of 15.6 +/- 3.7 days). When 5 X 10(7) donor strain spleen cells were injected i.v. at the time of transplantation, all purified islet grafts were acutely rejected within 9 days. In addition, the rejection time of the purified islet allografts was inversely correlated with the number of donor spleen cells injected. These results indicate that contaminating tissues such as lymph nodes, vascular tissue, and ductal fragments present in the crude digested islet allografts are a major stimulus for induction of an immune response resulting in acute rejection of islet allografts.

Animals↗

Clear cell chondrosarcoma. A report of two cases and review of literature.

Two cases of clear cell chondrosarcoma located in the distal femur and proximal humerus are reported. Both patients were men aged 35 and 51 years. Their initial symptom was a pathologic fracture. Roentgenographically, one patient showed a purely lytic lesion and another lytic with centrally radiodensity. Microscopic examination revealed that the tumor cells have a centrally placed vesicular nucleus surrounded by a clear cytoplasm, with distinct boundaries. Their cytoplasm stained with S-100 protein by the peroxidase-antiperoxidase method. We found 36 reported cases (including the two reported here), and delineated the clinico-pathologic characteristics of the disease.

Adult↗

Mechanism of central hyperglycemic effect of cholinergic agonists in fasted rats.

The influence of cholinergic agonists on central nervous system (CNS) regulation of blood sugar homeostasis was studied in fasted rats. When carbachol, muscarine, bethanechol, methacholine, or neostigmine was injected into the third cerebral ventricle, it caused a dose-dependent increase in the hepatic venous plasma glucose concentration. However, in the case of 1,1-dimethylphenyl-4-piperazinium iodide (DMPP) or nicotine, the level of hepatic venous glucose did not differ from that of the saline-treated control rats. The increase in glucose level caused by neostigmine was dose-dependently suppressed by coadministration of atropine. These facts suggest that cholinergic activation of muscarinic receptors in the CNS plays a role in increasing hepatic glucose output. Injection of neostigmine (5 X 10(-8) mol), an inhibitor of cholinesterase, into the ventricle resulted in the increase of not only glucose, but also glucagon, epinephrine, and norepinephrine in the hepatic venous plasma. However, constant infusion of somatostatin through a femoral vein completely prevented the increase of glucagon after administration of neostigmine, although the increase of hepatic venous glucose and epinephrine levels were still observed. Neostigmine-induced increments in glucose did not occur in adrenalectomized rats. This suggests that the secreted epinephrine acts directly on the liver to increase hepatic glucose output.

Adrenalectomy↗

Increase in plasma glucose concentration after intracerebroventricular injection of N,O'-dibutyryl cyclic adenosine 3',5'-monophosphate.

The effect of chemical stimulation of the central nervous system was studied in anesthetized rats. (Bu)2 cAMP, cAMP, 5'-adenosine monophosphate (AMP), ATP, and (Bu)2 N6,O2-dibutyryl guanosine-3'5'-cyclic monophosphate sodium salt were injected directly into the third cerebral ventricle, and changes in hepatic venous plasma glucose, immunoreactive glucagon, and insulin concentrations were studied. The injection of (Bu)2cAMP (1 X 10(-8) to 5 X 10(-7) mol/microliter saline) into the third cerebral ventricle caused a dose-dependent hyperglycemia associated with increased immunoreactive glucagon. (Bu)2cAMP-induced hyperglycemia and hyperglucagonemia were inhibited by prior bilateral adrenalectomy. The injection of somatostatin (1 X 10(-9) mol) with (Bu)2cAMP (5 X 10(-7) mol) into the third cerebral ventricle abolished both (Bu)2cAMP-induced hyperglycemia and an increase of glucagon secretion. These results suggest that cAMP may act intracellularly within the central nervous system to increase hepatic glucose output, and this appears to depend on the adrenal gland. Epinephrine secreted from the adrenal gland may directly act on the liver or enhance glucagon secretion, which in turn increases hepatic glucose output.

Adenosine Triphosphate↗

Compliance of human pulmonary "venous" system estimated from pulmonary artery wedge pressure tracings--comparison with pulmonary arterial compliance.

To evaluate the reservoir function of the pulmonary vascular bed for the left ventricle, the compliance of the pulmonary "venous" system (Cp'v') (consisting of the pulmonary veins and the left atrium) and that of the pulmonary arterial system (Cpa) were sequentially estimated in each of 31 subjects by using Hirakawa's and Engelberg's methods, respectively. In control cases (n = 6), Cpa was 6.68 +/- 3.52 (mean +/- SD) ml/mmHg and Cp'v' was 15.81 +/- 6.85 ml/mmHg. In patients with mitral stenosis (MS) of Class I (previous classification of NYHA) (n = 7), Cpa was 4.05 +/- 2.71 ml/mmHg and Cp'v' was 13.15 +/- 4.51 ml/mmHg. In patients with MS of Class II (n = 13), Cpa was 2.81 +/- 1.05 ml/mmHg and Cp'v' was 8.40 +/- 2.95 ml/mmHg. In MS of Class III (n = 5), Cpa was 1.54 +/- 0.80 ml/mmHg and Cp'v' was 7.10 +/- 1.91 ml/mmHg. These results indicate that both systems become less compliant as the cardiac functional capacity deteriorates. The ratio of Cp'v' to Cpa (Cp'v'/Cpa) was 2.7 +/- 1.1 in control cases, 3.9 +/- 1.4 in MS of Class I, 3.4 +/- 1.6 in MS of Class II and 5.3 +/- 2.1 in MS of Class III. When one compares these results with the compliance in the systemic circulation, i.e., 118 ml/mmHg in the veins and 2.5 ml/mmHg in the arteries, giving the ratio of 118/2.5 not equal to 50, it is obvious that the compliance of the pulmonary arterial system shares a sizable portion of the total compliance in the pulmonary vascular bed. The relationship between Cp'v' and the internal pressure, namely the mean pulmonary artery wedge (PAW) pressure, was expressed with a regression equation of, Cp'v' = 1/(0.003 PAW + 0.080), indicating that Cp'v' is inversely related to the internal pressure. In 12 of patients with MS, sublingual nitroglycerin shifted the Cp'v'-PAW pressure plots upwards and to the left, roughly along the Cp'v'-PAW regression curve for the entire groups of MS.

Adolescent↗

[Effect of propranolol on intractable ascites following liver resection].

Hepatic and respiratory failure, common complications following liver resection for hepatocellular carcinoma (HCC), especially when it is combined with liver cirrhosis, can be overcome by careful management of the circulatory and respiratory systems. Another common complication is intractable ascites which resists conventional therapy, such as, diuretics and protein replacement. Here we report a case in which intractable ascites was successfully treated with propranolol. The patient, a 48-year-old man who underwent liver resection for HCC combined with cirrhosis, started to suffer from ascites about 1 week after surgery. Upon administration of propranolol (1 mg/kg/day) with furosemide, his body weight decreased 500 g/day, returning to the preoperative value in 2 weeks in parallel with the normalization of the PRA. No side effects were observed during the medication period. Propranolol, a beta-adrenergic antagonist, is thought to suppress renin secretion from the juxtaglomerular apparatus in the kidney by blocking its beta-adrenergic receptor, thus suppressing the entire renin-angiotensin-aldosterone system. We concluded that propranolol is a promising drug for intractable ascites encountered with liver cirrhosis.

Adrenergic beta-Antagonists↗

[Massive osteoplastic bone metastasis of hepatocellular carcinoma--a case report].

Massive osteoplastic bone tumor in hepatocellular carcinoma is very rare. A 48-year-old man was misdiagnosed as osteosarcoma of the right proximal tibia with dense sclerosis and marked periosteal spiculation. Histologically, there were many osteoids and immature trabeculi. Tumor cells with spindle nuclei were not atypical and had few mitoses. Three years later, he suddenly died of rupture of cerebral aneurysm. Autopsy revealed small hepatocellular carcinoma with distant metastases of the tibia, lumbar spine and lung. In this case, it was extremely difficult to decide whether or not we were dealing with primary malignant tumor.

Bone Neoplasms↗

Hypoglycemic activity of MTP-1403 (2-amino-7,8-dihydro-4-piperazinyl-6H-thiopyrano 3,2-d pyrimidine), a new hypoglycemic agent.

2-Amino-7,8-dihydro-4-piperazinyl-6H-thiopyrano 3,2-d pyrimidine (MTP-1403) is a new oral hypoglycemic agent structurally different from any existing hypoglycemic drugs. MTP-1403 lowered fasting plasma level and dose-dependently improved glucose tolerance test without increasing insulin secretory response to glucose. MTP-1403 caused a decrease in fasting plasma glucose level in mild alloxan-induced diabetic rats but not in the rats suffering from ketosis. MTP-1403 markedly improved the oral glucose tolerance test in the genetically diabetic KK mice. These results suggest that hypoglycemic activity of MTP-1403 may be mechanically different from sulfonylureas and biguanides and beneficial to type II diabetics with hyperinsulinemia and insulin resistance.

Animals↗