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Biomedical subjects

N Sakamoto

Publications and source records attributed to N Sakamoto.

At least 289 records · Page 16Linked to original sources

Alpha-fetoprotein (AFP)-producing gastric carcinoma. Is it hepatoid differentiation?

Biochemical and immunohistochemical analyses were done on five cases of gastric carcinoma with excessive production of alpha-fetoprotein (AFP). Histologic and ultrastructural examination of these cases showed conventional poorly differentiated adenocarcinoma of cuboidal or polygonal tumor cells in the medullary area with scattered AFP-positive cancer cells. Comparative studies on serum AFP between these cases and in hepatocellular carcinoma (HCC) or in testicular yolk sac tumor cases using concanavalin A (ConA)-affinity and lens culinalis agglutinin A (LCA)-affinity sepharose columns revealed that the AFP derived from four cases had a high ConA nonadsorping rate and high LCA-reactive fraction similar to that of yolk sac tumor. The AFP from one case had a small LCA-reactive fraction similar to that of HCC. Further immunohistochemical study using several markers for liver cells or germ cell tumor did not show additional evidence of these tumor cells to differentiate into liver cells or yolk sac tumor cells. Thus, this study indicates that AFP-producing gastric carcinomas are not always derived from hepatoid differentiation of the foregut. These gastric carcinomas might be categorized into medullary tumor with gastrointestinal tract-specific AFP.

Adenocarcinoma↗

Neither adrenergic nor cholinergic antagonists in the central nervous system affect 2-deoxy-D-glucose(2-DG)-induced hyperglycemia.

To investigate whether the brain adrenergic and cholinergic neurotransmitter systems are involved in the regulation of 2-deoxy-D-glucose (2-DG)-induced hyperglycemia, we studied the effects of adrenergic and cholinergic antagonists on 2-DG-induced secretion of epinephrine and glucagon, and hyperglycemia, in anesthetized fed rats. When 2-DG (10 mg/10 microliters) was injected into the third cerebral ventricle, hepatic venous plasma glucose, glucagon, and epinephrine concentrations were significantly increased. Co-administration of phentolamine, propranolol, atropine and hexamethonium (1 X 10(-7) mol) with 2-DG did not modify the hyperglycemia and hormonal responses normally observed after the administration of 2-DG alone. From this evidence we concluded that neither brain adrenoceptive nor cholinoceptive neurons are involved in the regulation of 2-DG-induced hyperglycemia.

Adrenergic Fibers↗

[In vivo insulin sensitivity in adrenodemedullated rats].

Insulin sensitivity and responsiveness were determined in adrenal demedullated rats (ADMX) with euglycemic insulin clamp technique. Adrenal medulla was extirpated bilaterally a week before the study. Catheters were placed at right atrium via right jugular vein for sampling blood and at inferior vena cava via femoral vein for the infusion of insulin and glucose solution. Insulin was infused at rates of 4.4, 8.8, 14.7, 29.3, 88.0, 293.0 mU/kg/min. Blood was collected every five min. during the clamp and glucose infusion rate was modulated to control the blood glucose concentrations at fasting levels. Glucose metabolism was calculated from the amount of glucose infused from 60th to 120th min. during the euglycemic clamp. The results obtained were as follows: 1. Glucose metabolisms of ADMX in each infusion rate of insulin, 4.4, 8.8, 14.7, 29.3, 88.0, 293.0 mU/kg/min were 5.2 +/- 0.5, 12.5 +/- 0.5, 17.6 +/- 1.2, 19.8 +/- 2.3, 29.0 +/- 1.5, and 25.2 +/- 1.9 mg/kg/min, respectively. 2. Glucose metabolisms of control group in each dose were 6.6 +/- 0.4, 9.0 +/- 0.9, 18.5 +/- 1.2, 23.4 +/- 2.4, 24.6 +/- 1.1, and 27.0 +/- 1.3 mg/kg/min, respectively. 3. Significant difference (p less than 0.01) in glucose metabolism between ADMX and control was observed at the insulin infusion rate of 8.8 mU/kg/min which might be equivalent to physiological hyperinsulinemia. 4. There were not any differences in insulin responsiveness between both groups. These results suggest that epinephrine regulates insulin sensitivity under physiological hyperinsulinemic condition via defects of insulin receptors.

Adrenal Medulla↗

Neostigmine-induced hyperglycemia is mediated by central muscarinic receptor in fed rats.

We previously reported that neostigmine injected into the third cerebral ventricle stimulated adrenal secretion of epinephrine, secretion of glucagon from the pancreas, and direct neural innervation of the liver, resulting in hepatic venous plasma hyperglycemia in anesthetized fed rats. However, receptor type of these 3 mechanisms is not known. Therefore, we examined the effects of intraventricularly injected cholinergic or adrenergic antagonists on neostigmine-induced catecholamines in intact rats, glucagon secretion which is mediated by direct neural innervation of pancreas in bilateral adrenalectomized (ADX) rats, and hepatic venous hyperglycemia which is mediated by direct neural innervation of liver in ADX rats receiving constant infusion of somatostatin from femoral vein. Atropine injected into the third cerebral ventricle suppressed epinephrine secretion and dose-dependently inhibited hepatic venous hyperglycemia induced by neostigmine in intact rats. The neostigmine-induced glucagon secretion which occurs in ADX rats was suppressed by atropine. Atropine also prevented the neostigmine-induced hyperglycemia in ADX rats receiving constant somatostatin infusion through femoral vein (ADX-Somato rats). On the other hand, phentolamine, propranolol and hexamethonium showed no significant inhibitory effect on neostigmine-induced hyperglycemia, epinephrine and glucagon secretion in intact rats, glucagon secretion in ADX rats, or hyperglycemia in ADX-Somato rats. These results suggest that neostigmine-induced epinephrine and glucagon secretion and increased hepatic glucose output stimulated by direct neural innervation to liver is mediated by central muscarinic receptor in fed rats.

Adrenergic Fibers↗

Increased renal scarring by bacteria with mannose-sensitive pili.

Renal scars are thought to be the end stage of chronic pyelonephritis and one of the most important causes of renal insufficiency and renal hypertension. The role of bacterial pili was examined in scar formation after an infection of newly constructed bacterial strains using the recombinant DNA technique, which possessed either mannose resistant (MR) or mannose sensitive (MS) pili of Serratia marcescens. Strains that differed in only a single virulence factor, namely, MR or MS pili, were used in a rat model of chronic pyelonephritis. In this model, MS-piliated bacteria stimulated renal scarring more severely than non-piliated or MR-piliated bacteria.

Animals↗

Current progress in clinical trials of aldose reductase inhibitors in Japan.

In addition to the results of our clinical trial of epalrestat in diabetic retinopathy (the open study), the current progress in the clinical trials of aldose reductase inhibitors for the 'triopathy' of complications (neuropathy, retinopathy and nephropathy) in Japan is reported. No data from the placebo-controlled double-blind studies in Japan are shown because a detailed analysis of the effects of epalrestat on diabetic neuropathy and retinopathy is now under way. However, it must be stressed that in the phase III placebo-controlled double-blind studies in neuropathy and retinopathy, epalrestat was effective.

Aldehyde Reductase↗

Asymptomatic primary sclerosing cholangitis treated with ursodeoxycholic acid.

Ursodeoxycholic acid treatment (600 mg/day) was evaluated in a patient with asymptomatic primary sclerosing cholangitis. Serum levels of biliary enzymes decreased to normal ranges within 1 month's treatment and remained normal for 26 months. Serum chenodeoxycholic acid had been replaced by ursodeoxycholic acid, and hepatic copper metabolism, assessed by x-ray probe analysis, improved during the treatment. However, neither biliary tract sclerosis nor portal tract pathology changed with the treatment. These observations suggest that ursodeoxycholic acid protects the liver in primary sclerosing cholangitis by improving the metabolism of bile acid and copper.

Adult↗

The effects of a new immunosuppressive agent, FK506, on the glomerular injury in rats with accelerated nephrotoxic serum glomerulonephritis.

The aim of the present work was to study the effects of a new immunosuppressive drug, FK506, in accelerated nephrotoxic serum glomerulonephritis. Glomerulonephritis was induced in female Wistar rats by the preimmunization with normal rabbit IgG (Day-4) and the subsequent intravenous injection of rabbit anti-GBM serum (Day 0). Without treatment with FK506, rats developed proteinuria at Day 6 and onward. Rat anti-rabbit IgG was strongly detected at Day 6 and the titer was maintained through Day 20. Moderate hypercellularity and focal crescent formation were observed at Day 20. Rats injected intramuscularly with 0.3 or 1 mg/kg of FK506 did not develop proteinuria and the anti-rabbit IgG titer was much less or was undetectable throughout the experiments. These data suggest that FK506 is effective in the present model of glomerulonephritis.

Animals↗

Linear feedback control of acetylcholine level in the presynaptic terminal.

A dynamic analysis of acetylcholine (ACh) level during nervous signal transmission was performed by means of computer simulation. The rate equation expressed in a system of non-linear ordinary differential equations represents the dynamic aspects of the fundamental metabolic processes in the chemical transmission at the synapse in terms of the relevant metabolite fluxes and the reactions of choline acetyltransferase, ACh receptor and acetylcholinesterase functioning in two putative homogeneous and open compartments. After a transmitter release, the ACh level in the presynaptic terminal cannot be restored by supplying the substrates of acetyl-CoA (AcCoA) and choline (Ch) at constant influx rates for ACh synthesis. A simple regulatory mechanism of linear feedback of the ACh level for variation of the substrate influx rates can accomplish the desired replenishment of ACh, in which the influx rate of AcCoA characterizes the response speed and its ratio to that of Ch governs the maintenance of the ACh level. The CoA level is ineffective for this regulatory mechanism.

Acetylcholine↗

Suitability of colchicine and superoxide dismutase for the suppression of renal scarring following an infection with bacteria showing mannose-sensitive pili.

Two new strains of Serratia marcescens were constructed by the gene manipulation method from the clinical isolate US 46, which has two kinds of pili--mannose-sensitive (MS) and mannose-resistant (MR) ones--on the cell surface. After cloning the genes of the MS and MR pili, either the MS or the MR gene was transferred to the nonpiliated Escherichia coli, and MS- or MR-piliated strains were obtained. In the experimental pyelonephritis model of rats, MS- or MR-piliated bacteria were inoculated directly to the renal parenchyma, and the following results were obtained. MS-piliated rather than MR-piliated strains stimulated severe scarring of the kidney, and this scarring was suppressed by treatment with colchicine or superoxide dismutase (SOD) during an early stage of the infection. These findings suggest that MS-piliated bacteria stimulated polymorphonuclear leukocytes, which released large amounts of superoxide resulting in renal scarring. SOD was hoped to be a drug capable of preventing renal scarring, and such a result was successfully obtained.

Animals↗

Evaluation of flow electromyography in patients with benign prostatic hyperplasia.

Combined uroflowmetry and external sphincter electromyography studies were done both preoperatively and postoperatively in patients with benign prostatic hyperplasia. In 56 patients preoperative electromyography during voiding showed silent or markedly suppressed activity in 41 patients (73.2%), while the remaining 15 patients (27.8%) revealed active electromyography. In the postoperative studies, 12 patients revealed active electromyography even after the release of obstruction. The urine flow rate following operation was not drastically improved in the active electromyography group compared to the silent electromyography group. We suppose that long-term urethral obstruction with prostatic adenoma could influence the function of relaxation of the external sphincter muscle in some patients with benign prostatic hyperplasia.

Aged↗

A plasma membrane antigen of rat glomerular epithelial cells. Antigenic determinants involving N-linked sugar residues in a 140-kilodalton sialoglycoprotein of the podocytes.

The aim of the present study was to investigate the antigenic make up of the plasma membrane of rat glomerular visceral epithelial cells (GEP). A crude plasma membrane fraction (PM) was extracted by 1% sodium dioxycholate from isolated rat glomeruli. PM was digested with neuraminidase (NRD) and purified by the Helix pomatia agglutinin (HPA)-affinity column. When studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the HPA-affinity purified plasma membrane fraction (HPA-PM) formed two bands, a main band of 160 kilodaltons (kd) and a smaller band of 40 kd. By Western blot analysis, the antibodies raised in a rabbit against HPA-PM (RbAHPA-PM) reacted only with the 160-kd protein of HPA-PM, or with the relevant 140-kd protein of PM when PM was digested by NRD. The 140-kd protein of PM was reactive with wheat germ agglutinin and, when treated with NRD, was reactive with HPA and peanut lectin. The 160-kd protein of HPA-PM was degraded by endoglycosidase-F and lost its reactivity with RbAHPA-PM. These results suggest that RbAHPA-PM react with antigenic sites involving N-linked sugar residues of a 140-kd sialoglycoprotein, presumably podocalyxin. Immunohistochemical studies using normal rat kidney tissues treated with NRD as substratum showed that RbAHPA-PM bound to the free surface of GEP but not with soles of the foot processes or with other structures of the kidney. In rats intravenously injected with NRD and subsequently with RbAHPA-PM, antibodies were rapidly fixed (within 1 hour) to the free surface of GEP. Immunofluorescence study showed that RbAHPA-PM also reacted with human glomeruli after treatment with NRD. These results suggest that GEP express surface sugar residues that are potential targets for direct immunologic attack.

Animals↗

[CT findings of watershed infarction; comparison of 123I-IMP SPECT and IV-DSA].

A watershed infarction is a specific type of a cerebral infarction. This occurs at the border zone between major cerebral arteries. Its CT findings are characteristic as a wedge shaped low density appearing either in the superior frontal region (watershed between anterior and middle and posterior cerebral artery), and always involving the deep white matter onto the ventricle wall. Even though the CT feature is small, a patient, without exception, suffers from neurologic deficit. We studied four cases of a watershed infarction on X-ray CT and compared with 123I-IMP SPECT. DSA was also made to demonstrate an obstruction of an artery which was usually found at the more proximal segment then what we expected from the CT feature. The findings on the 123I-IMP SPECT were better predictable of neurologic symptoms and they were larger in extent than the CT findings.

Aged↗

[Hodgkin's disease associated with Tolosa-Hunt syndrome].

A thirty-eight-year-old man developed gradually progressing right retro-orbital pain, diplopia on the left lateral gaze, and left ptosis. On examination paresthesia was present on the first division of right trigeminal nerve. Orbital venography revealed obstruction of right superior orbital vein on the entering portion to the cavernous sinus. A daily administration of 30 mg of prednisolone resulted in a rapid improvement of the symptoms. Diagnosis of Tolosa-Hunt syndrome was made on the basis of neurological symptoms, roentgenographic findings and responsiveness to prednisolone. One year later, weakness of right leg accompanied with left cervical and axillary lymphadenopathy was developed. A biopsy specimen of cervical lymph node was identical with the Hodgkin's disease, lymphocyte predominance type. He was treated with COPP regimen; lymphadenopathy decreased in size. We reported a rare case of Hodgkin's disease preceded by Tolosa-hunt syndrome which might be caused by the extranodal lesions.

Adult↗

Invasive character of malignant endothelial cells in vinyl-chloride-induced liver angiosarcoma.

Two cases of vinyl-chloride-induced angiosarcoma of the liver were investigated with special reference to the invasive character of malignant endothelial cells. Histological findings of the liver were similar in both cases. The liver angiosarcoma was multicentric and consisted of three portions: a peripheral parenchymal area, an intermediate mottled area, and a central cavernous area. Microscopically the intermediate area showed a mixture of fibrosis and cell infiltration of various patterns. At the periphery, yellowish brown parenchymal tissues remained and were always associated with sinusoidal changes, from non-cellular dilatation to trabecular growth of the small round cells. Under electron microscope, the small round cells showed direct contact with red blood cells and hepatocytes. Thus, the sinusoidal small cell infiltration is thought to be an initial lesion of angiosarcomatous transformation. Because none of the liver is free from these sinusoidal changes, partial hepatectomy would not be indicated even in a patient with few cavernous lesions.

Endothelium↗