Search PubMed⌕ Search

Biomedical subjects

N Sakamoto

Publications and source records attributed to N Sakamoto.

At least 307 records · Page 17Linked to original sources
PubMed1989

Antitumor effects of an antiangiogenic polysaccharide from an Arthrobacter species with or without a steroid.

A sulfated polysaccharide-peptidoglycan complex, DS-4152, isolated from the culture supernatant of an Arthrobacter species inhibited angiogenesis and tumor growth and enhanced the antiangiogenic activity of 11 steroid hormones by 2 to 100 times. In the presence of cortisone acetate or tetrahydro S, DS-4152 suppressed chick chorioallantoic membrane angiogenesis and murine tumor M5076 cell-induced s.c. angiogenesis. The antitumor effects of DS-4152 administered in combination with a steroid whose dose level did not affect tumor growth were examined. DS-4152 significantly inhibited the growth of s.c.-implanted B16 melanoma in combination with cortisone acetate. DS-4152 plus tetrahydro S inhibited the growth of s.c. solid tumors and prolonged the survival time of mice bearing highly metastasizing M5076. The body weight increase was not affected by any administration. On the other hand, the survival of mice with ascitic M5076 tumors was not affected by the combination of DS-4152 plus tetrahydro S. The antiangiogenic activity of DS-4152 was more potent than that of heparin. Furthermore, DS-4152 is an angiogenesis inhibitor by itself, without steroid hormones. Successive s.c. treatment with heparin caused hemorrhagic death, but with DS-4152, suppressed tumor growth without reducing body weight.

Animals↗
PubMed1989

Vagally mediated insulin secretion by stimulation of brain cholinergic neurons with neostigmine in bilateral adrenalectomized rats.

This study investigated the relationship between central cholinergic neurons and insulin secretion in bilateral adrenalectomized fed rats. Neostigmine (a cholinesterase inhibitor, 5 x 10(-8) mol) administered into the third cerebral ventricle produced significant increases in hepatic venous plasma insulin and glucose concentrations, whereas i.v. injection of the same dose of neostigmine did not. Prior acute subdiaphragmatic vagotomy or i.p. pre-injection with methylatropine (10(-8) mol) completely prevented the neostigmine-induced rise in plasma insulin concentration. Intraperitoneal pretreatment with hexamethonium (5 x 10(-8) mol) also significantly reduced the plasma insulin response. These peripheral pretreatments did not change the plasma glucose response to neostigmine. Intraventricular co-administration of 10(-9) mol methylatropine, a dose that was ineffective when pre-injected i.p., eliminated the plasma insulin and glucose responses to neostigmine, whereas hexamethonium (5 x 10(-8) mol) had no influence on either response to neostigmine. These observations suggest that stimulation of central cholinergic-muscarinic neurons with third cerebral ventricular injection of neostigmine results in vagally mediated insulin secretion in bilateral adrenalectomized fed rats.

Adrenalectomy↗
PubMed1989

A rare case of recurrent vasodepressive attacks of 2-hours duration: analysis of the mechanism by muscle sympathetic nerve activity recording.

Muscle sympathetic nerve activity was recorded in a 57-year-old male patient suffering from severe hypotensive attacks with bradycardia for 10 years. Continuous blood pressure recording demonstrated frequent drastic falls in pressure. Disappearance and reappearance of muscle sympathetic nerve activity coincided with the onset and termination of attacks. Awakening from sleep or emotional and/or cardiovascular stress seems to trigger hypotension. Cardiac pacemaker was not useful in limiting the attack, because right ventricular pacing caused abrupt falls in both blood pressure and heart rate.

Bradycardia↗
PubMed1989

Interferon alpha and gamma positive mononuclear cells and HLA antigen expression on hepatocyte membrane in the liver in chronic type B and non-A, non-B hepatitis.

To evaluate the role of local interferon on pathogenesis in chronic type B and non-A, non-B chronic hepatitis, we examined the cellular localization of interferon alpha and gamma, and the expression of HLA antigens in cryostat liver sections from 33 chronic carriers of HBs antigen and 10 patients with non-A, non-B chronic hepatitis, using an immunoperoxidase procedure with monoclonal antibodies. Infiltrating mononuclear cells were the main cell element staining positive for interferon alpha or gamma. Among type B chronic liver disease, the percentages of both interferon alpha- and gamma-positive mononuclear cells were highest in patients with chronic active hepatitis, and their levels were higher in patients who had serum HBe antigen, indicating that local expression of interferon closely correlates with activity of disease and virus replication. On the other hand, both the frequency of interferon alpha or gamma positive cells, and the intensity of HLA class I antigens on hepatocytes were much lower in patients with non-A, non-B, chronic active hepatitis in comparison with those with type B chronic active hepatitis. These findings suggested that locally produced interferons have role of varying degrees on the host defence mechanism in chronic hepatitis, reflecting disease activity and the etiology of the disease.

Adult↗
PubMed1989

Central nervous system control of glycogenolysis and gluconeogenesis in fed and fasted rat liver.

The influence of brain cholinergic activation on hepatic glycogenolysis and gluconeogenesis was studied in fed and 48-hour fasted rats. Neostigmine was injected into the third cerebral ventricle and hepatic venous plasma glucose, glucagon, insulin, and epinephrine were measured. The activity of hepatic phosphorylase-a and phosphoenolpyruvate-carboxykinase (PEP-CK) was also measured. Experimental groups: 1, intact rats; 2, rats infused with somatostatin through the femoral vein; 3, bilateral adrenodemedullated (ADMX) rats; 4, somatostatin infused ADMX rats; 5, 5-methoxyindole-2-carboxylic acid (MICA) was injected intraperitoneally 30 minutes before injection of neostigmine into the third cerebral ventricle of intact rats. MICA treatment completely suppressed the increase in hepatic glucose in fasted rats, but had no effect in fed rats. Phosphorylase-a activity was not changed in fasted rats, but increased in fed rats, intact rats, somatostatin-infused rats, somatostatin-infused ADMX rats, and ADMX rats in that order. PEP-CK was not changed in fed rats, but increased at 60 and 120 minutes after neostigmine injection into the third cerebral ventricle in fasted rats. We conclude that, in fed states, brain cholinergic activation causes glycogenolysis by epinephrine, glucagon, and direct neural innervation. In fasted states, on the other hand, gluconeogenesis is dependent on epinephrine alone to increase hepatic glucose output.

Adrenal Medulla↗
PubMed1989

Experimental glomerulonephritis induced in rats by a lectin and its antibodies.

The aim of the present study was to investigate the events following interaction of antibody with an antigen planted on the surface of glomerular endothelial cell (GEN). A lectin, Helix pomatia agglutinin (HPA), was planted at the surface of rat GEN by the perfusion of the isolated left kidney with neuraminidase (NRD) and HPA. A subsequent perfusion with IgG fraction, but not with Fab fragments, of rabbit anti-HPA serum induced formation of granular immune deposits (IDs) on the surface of GEN. When the left kidney was revascularized after initial formation of IDs, acute glomerulonephritis ensued. Fifteen minutes after revascularization, granular IDs were observed at the subendothelial space. Two days later, there was decrease of subendothelial IDs with concomitant appearance of subepithelial IDs. At the seventh day, IDs were mainly localized in the subepithelial space. The results suggest that this model of experimental glomerulonephritis is characterized by: (1) initial formation of HPA immune complexes (ICs) at the surface of GEN; and by (2) subsequent movement of ICs from luminal side to subepithelial area with local formation of IDs. The results are relevant to the understanding of the kinetics of ICs resulting from interaction of antibodies with exogenous antigens "planted" in the glomerular capillary walls, and of the local formation of IDs.

Animals↗
PubMed1989

A case of nephrotic syndrome with glomerular lipoprotein deposition with capillary ballooning and mesangiolysis.

A 33-year-old man with nephrotic syndrome and rapid deterioration of renal function showed curious glomerular morphological abnormalities. Ballooning of the glomerular capillaries due to a substance accumulated in the capillary lumina and mesangiolysis were prominent histological features. The deposits in the capillary lumen were positive for Sudan III staining, and also for beta-lipoprotein, apoprotein B and apoprotein E by immunofluorescent technique. The staining of beta-lipoprotein in a flower leaf pattern was a striking characteristic, while such staining was negative when studied in 20 patients with nephrotic syndrome who were used as controls. Based on these findings, the morphological abnormalities in this case were considered to be related to lipoprotein deposition in the glomeruli. This case is thought to be the first reported in a complete form in the literature which could be classified as a new kind of disease related to lipoprotein metabolism abnormalities.

Adult↗
PubMed1989

The relative importance of nervous system and hormones to the 2-deoxy-D-glucose-induced hyperglycemia in fed rats.

We examined the relative contributions of hormones and nervous system to the total 2-deoxy-D-glucose (2-DG)-induced central nervous system-mediated hyperglycemia. 2-DG was injected into the third cerebral ventricle in the following four groups of rats, and hepatic venous plasma glucose, immunoreactive glucagon, immunoreactive insulin, epinephrine, and norepinephrine were measured: 1) intact rats; 2) intact rats receiving somatostatin with insulin infusion through the femoral vein to inhibit glucagon secretion and maintain the basal insulin level; 3) bilateral adrenalectomized (ADX) rats to prevent epinephrine secretion; and 4) ADX rats receiving somatostatin with insulin infusion. Comparing areas under glucose curves among the intact rats, those receiving somatostatin with insulin infusion, ADX rats, and ADX rats receiving somatostatin with insulin infusion, the area under the glucose curve was intact rats greater than intact rats receiving somatostatin with insulin infusion greater than ADX rats receiving somatostatin with insulin infusion greater than ADX rats. These results suggest that there are three distinct sympathetic nervous system responses to 2-DG-induced central nervous system-mediated hyperglycemia. 2-DG-induced hyperglycemia is not dependent on only one of those three systems, it is dependent on all of them. The relative potency of the factors to 2-DG-induced hyperglycemia increases in the following order: direct neural innervation of liver (including suppressive epinephrine action on insulin secretion), glucagon, and direct epinephrine action on liver.

Adrenalectomy↗
PubMed1989

Involvement of the hippocampus in central nervous system-mediated glucoregulation in rats.

To find out whether the hippocampus is involved in central nervous system-mediated glucoregulation, we injected saline, neostigmine, dopamine, norepinephrine, bombesin, beta-endorphin, somatostatin, and prostaglandin F2 alpha into the dorsal hippocampus in anesthetized fed rats. After injection of dopamine, norepinephrine, bombesin, beta-endorphin, somatostatin, or prostaglandin F2 alpha, the level of hepatic venous plasma glucose did not differ from that in saline-treated control rats. However, neostigmine, an inhibitor of acetylcholine esterase, caused a dose-dependent increase in the hepatic venous plasma glucose concentration. This neostigmine-induced hyperglycemia was dose-dependently suppressed by coadministration of atropine, but not by hexamethonium. Injection of neostigmine (5 X 10(-8) mol) resulted in an increase not only in glucose but also in glucagon, epinephrine, and norepinephrine in hepatic venous plasma. In bilateral adrenalectomized rats, neostigmine-induced hyperglycemia was suppressed, but the hepatic venous plasma glucose concentration still increased significantly. These results indicate that the hippocampus is involved in central nervous system-mediated glucoregulation through cholinergic muscarinic activation, partly via epinephrine secretion.

Adrenalectomy↗
PubMed1989

Central nervous system-mediated glucagon secretion is enhanced by alpha 2-adrenoreceptor activation.

We assessed the response of the adrenergic receptor in pancreatic glucagon secretion to central nervous system stimulation. Injection of neostigmine (5 x 10(-8) mol) into the third cerebral ventricle in intact rats resulted in increased epinephrine and norepinephrine secretion associated with glucagon secretion. This glucagon secretion was still observed in bilateral adrenalectomized (ADX) rats, although its concentration was significantly lower than that in the intact rats. This glucagon rise was significantly inhibited by ip treatment of ganglionic blocker with hexamethonium. Intraperitoneal injection of alpha-adrenergic receptor antagonist phentolamine (5 x 10(-7) mol), but not of beta-adrenergic receptor antagonist propranolol (1 x 10(-6) mol), reduced the hyperglucagonemic effect of a subsequent neostigmine injection in intact and ADX rats, although these antagonists did not influence epinephrine or norepinephrine secretion in intact rats. In addition, ip injection of the selective alpha 2-receptor antagonist yohimbine (5 x 10(-7) mol), but not of the selective alpha 1-receptor antagonist prazosin (1 x 10(-6) mol), inhibited the neostigmine-induced glucagon secretion in intact and ADX rats. From this evidence it is suggested that central nervous system-mediated glucagon release is enhanced by alpha 2-adrenoreceptor stimulation by either catecholamines or the autonomic nervous system.

Adrenalectomy↗
PubMed1989

Experimental atherosclerosis-like lesions induced by hyperinsulinism in Wistar rats.

To elucidate the possible role of hyperinsulinism in the etiology of diabetic macroangiopathy, we studied the long-term effects of insulin injection on the arterial wall of the rat both biochemically and histologically. Fifty male Wistar rats were divided into two groups. One group was subjected to daily injection of insulin-zinc suspension (20 U/kg), and the other group was treated with saline. After 1 yr, all the animals were killed, and the lipid contents in the intimal media of their aortas were determined. Parts of the ascending aortic tissues were further examined by use of either light or electron microscopy. The triglyceride content of the insulin-treated rat aortas was significantly (P less than .05) increased compared with that of the saline-treated rat aortas. As determined by light microscopy, the intimas of the aortas from the insulin-treated rats were significantly (P less than .001) thickened, and the subendothelial tissues consisted of eosinophilic fiber bundles, amorphous ground substances, and irregularly arranged cells. These cells were identified by electron microscopy as having smooth muscle cell origin. All these findings suggest that atherosclerosis-like lesions could be induced by long-term insulin injection in the aortas of the rat and that hyperinsulinism plays a certain role in the development of diabetic macroangiopathy.

Animals↗
PubMed1989

Heparan sulfate proteoglycan of murine glomerular basement membrane: relationship between localization of the core protein and localization of fixed negative charges.

Antibodies to a 250,000 molecular weight heparan sulfate proteoglycan (HSPG) core protein purified from PYS-2 cells were prepared in the rabbit. After absorption with laminin, the anti-HSPG serum (AHSPGS) was specific for HSPG by enzyme-linked immunoabsorbent assay (ELISA). Immunoelectron microscopy showed that AHSPGS reacted with the mouse glomerular basement membrane (GBM) or, more precisely, with three HSPG rich layers, i.e., (i) the lamina rara interna in a discrete or interrupted-linear pattern, (ii) the interface between the GBM and the soles of the foot processes, and (iii) the lamina rara externa in a finely discrete pattern. The localization of HSPG in the GBM was very similar to that of the fixed negative charges detected with polyethyleneimine (PEI). When mice were treated with heparitinase, binding of PEI was seen only on the cell surface including the foot process soles (ii) but not in the GBM (i and iii), while the localization of HSPG core protein was unaltered. These results suggest that the localization of the HSPG core protein was correlated with that of the fixed negative charges in the GBM (i and iii). The foot process base (ii) seems to be a complicated zone since the PEI binding in this area was less affected by heparitinase treatment, while this area has been reported to have a lower sialic acid content than the foot process surface facing the urinary space.

Animals↗
PubMed1989

Glomerular injury induced by antibodies against heparan sulfate proteoglycan (HSPG) derived from PYS 2 cells.

Kidneys of Balb/c mice intravenously injected with rabbit antibodies to heparan sulfate proteoglycan (HSPG) derived from PYS-2 cells were studied for 14 weeks. Antibodies were found to bind to the glomerular basement membrane (GBM) as early as 15 min after the injection. Binding of antibodies was observed over the whole thickness of the GBM. The lamina rara interna and foot process base appeared to be more intensely stained. This pattern did not change throughout the experiments. Mild inflammatory changes (infiltration of polymorphonuclear cells and swelling of the glomerular endothelium) were seen at the initial stage (approximately 1 day), and mesangial expansion followed (1-4 weeks). In mice pre- and booster-immunized with normal rabbit IgG, a moderate autologous response was observed by immunofluorescence microscopy, but no significant inflammatory changes were noted. At the late stage (6 weeks approximately), irregular GBM thickening was observed. The thickening was due mainly to expansion of the lamina rara externa. These findings suggest that the anti-HSPG antibodies caused mild glomerulonephritis at the initial stage, and later caused thickening of the GBM possibly by disturbing the assembly, production and degradation of GBM components.

Animals↗
PubMed1989

Effects of lipolytic and antilipolytic agents on glycerol and free fatty acid release from isolated adipocytes of normal and diabetic rats.

Isolated adipocytes from severely diabetic rats exhibited hypersensitivity to epinephrine at low concentrations (0.05-0.1 microM) on lipolysis, compared with isolated adipocytes from normal and mildly diabetic rats. Hypersensitivity to dibutyryl cyclic AMP and theophylline at concentrations from 0.05 to 0.50 mM was not observed in adipocytes of severely diabetic rats. Insulin could not exert an inhibitory effect on epinephrine-induced lipolysis in adipocytes of severely diabetic rats. In isolated adipocytes from normal rats, hyperosmolarity due to the combination of 50 mM glucose and 100 mM sodium chloride only had an inhibitory effect on 0.25 microM epinephrine-induced lipolysis. Ten mM beta-hydroxybutyrate did not inhibit lipolysis caused by epinephrine although any lipolysis stimulated by epinephrine, dibutyryl cyclic AMP and theophylline was inhibited by insulin. Our present findings may partly explain insulin resistance in the severely diabetic state and the pathogenesis of the absence of ketosis in hyperglycemic hyperosmolar conditions.

3-Hydroxybutyric Acid↗
PubMed1989

[Morphological study of innervation of orbicularis oculi in the cat with respect to motoneurons, nerve fibers and muscle fibers].

It has been suggested that the orbicularis oculi muscle functions in different modes of action in the orbital portion and in the palpebral portion. To study the anatomical correlation between the localization of muscular division and the size of motoneurons in facial nucleus, the retrograde tracing method was used. A histochemical study on the type of muscle fibers was also performed. The relationship between the motoneurons, nerve fiber and muscle fiber was discussed in terms of the functional organization of the palpebral or orbital orbicularis oculi. We injected a tracer of 50% horseradish peroxidase (HRP) into the orbital and/or palpebral portion of the orbicularis oculi muscle and HRP-labelled motoneurons at the brainstem were studied. In the facial nucleus, four subnuclei have been described: the ventrolateral, ventromedial, dorsolateral and dorsomedial. HRP-labelled motoneurons which innervated both the orbital and palpebral portions were spindle shaped and were found ipsilaterally in the dorsolateral subnucleus, and were distributed rostrocaudally. The histogram of the average soma diameter traced by the injection in the orbital portion presented two peaks at 30 microns and 40 microns in contrast to one peak of palpebral portion. Secondly, a histochemical study using alkali (pH 10.4) preincubated ATPase and acid (pH4.3) preincubated ATPase and NADH stain was performed. It was found that the muscle fibers of the orbital part were composed predominantly of large and middle diameter group II B, while the palpebral part consisted mainly of small diameter group II A. By diameter analyses of the facial nerve fibers, it was found that the myelinated nerve fibers consisted of 3 peaks in terms of the magnitude of histogram.

Animals↗