Search PubMed⌕ Search

Biomedical subjects

N Sakamoto

Publications and source records attributed to N Sakamoto.

538 records · Page 30Linked to original sources
PubMedDate not supplied

The specificity of human liver membrane lipoprotein: studies with monoclonal antibodies.

Hybrid cell lines which secreted antibodies to liver-specific membrane lipoprotein (LSP) were obtained by immunizing SMA and BALB/c mice with human LSP and fusing their splenocytes with the myeloma cell line P3-NSI/1-Ag4-1. The secretion of antibody to LSP (anti-LSP) was monitored by binding to a human hepatocellular carcinoma cell line, SK-Hep-1, which possesses surface membrane LSP, and to 125I-antimouse F(ab')2 antibody in radiobinding assay, and by reacting with 125I-LSP in double-antibody radioimmunoassay. From four separate cell fusions, seven secreting hybrids were cloned by dilutional techniques. Of these, four cell lines produced antibodies reacting with a wide variety of cells. The culture supernatants of the remaining three (6D6, 6G3 and 8F10) demonstrated the strongest binding activities against SK-Hep-1 among the various kinds of cell lines tested. However, binding with other cell lines, including renal cancer cells (SK-RC-6) and myeloid cell (HL-60) also occurred. Absorption test of ascitic fluids derived from 6D6 showed that ascitic fluids lost their capacity to bind to target SK-Hep-1 cells when absorbed with SK-Hep-1. Similarly absorption by SK-RC-6 and HL-60 removed almost all of the binding activity of ascitic fluids. Moreover, the binding activities of the ascitic fluids to SK-RC-6 and HL-60 were eliminated when absorbed with SK-RC-6, HL-60 and SK-Hep-1. The present study indicates that our LSP preparation contains nonspecific organ antigens, and although LSP exists on liver cell membrane, it is also found on the cell membrane of other organs albeit in less quantity.

Animals↗
PubMedDate not supplied

Relationship between regional myocardial blood flow and mitochondrial function.

The purpose of this study was to clarify the relationship between myocardial mitochondrial dysfunction and the degree plus duration of restricted coronary blood flow. 135 anesthetized and open-chest dogs were divided into 3 groups according to coronary occlusion time: 10, 20, and 60 min. Regional myocardial blood flow (MBF) was determined in both ischemic and nonischemic areas before and during coronary occlusion using the hydrogen gas clearance method. Myocardial mitochondria were prepared from each area in which MBF was determined after 10, 20, or 60 min of coronary ligation, and their respiratory control index (RCI), ADP/O, and rate of oxygen consumption in state III O2 (St. III O2) were measured. The MBF measured in 135 dogs before coronary ligation was 103 +/- 25 ml/min/100 g (mean +/- SD) for the area to be rendered ischemic and 101 +/- 24 ml/min/100 g for the control area. The MBF in the ischemic area did not cease completely following coronary ligation, and the distribution of MBF showed variations which seemed attributable to individual differences. In the 10-min group, no index of mitochondrial function of the ischemic area differed from that of the nonischemic area at any level of MBF. When MBF was less than 20 ml/min/100 g, RCI of mitochondria from the ischemic area was significantly lower than that from the nonischemic area, in the 20- and 60-min groups. When MBF was less than 20 ml/min/100 g, St. III O2 of mitochondria from the ischemic area significantly decreased compared with that from the nonischemic area, in the 20-min group. In the 60-min group, MBF less than 30 ml/min/100 g, St. III O2 of mitochondria from the ischemic area was likewise significantly decreased. Moreover, with MBF below 20 ml/min/100 g, both RCI and St. III O2 of mitochondria from the ischemic area were significantly lower in the 60-min group than in the 20-min group. These results indicate that ischemia-induced mitochondrial dysfunction depends on the degree of decrease in the blood flow of the area involved as well as on the duration of ischemia, and the blood flow that is critical for survival, based on mitochondrial function, is approximately 20 ml/min/100 g, i.e., a reduction to 20% of normal value.

Animals↗
PubMedDate not supplied

Primary Budd-Chiari syndrome due to complex venous anomalies.

A 35-year-old woman with clinical features of Budd-Chiari syndrome is presented. Abdominal ultrasonography, computed tomography, and venography disclosed that the venous congestion in this patient resulted from complex venous anomalies including azygos-hemiazygos continuation, absent superior hepatic veins, and retroaortic transposition of the left renal vein.

Adult↗
PubMedDate not supplied

Effects of glimepiride on in vivo insulin action in normal and diabetic rats.

To evaluate the effects of glimepiride on insulin action in peripheral tissues, we investigated insulin-induced glucose uptake in normal and diabetic rats using the euglycemic clamp procedure (insulin infusion rates: 6 and 30 mU/kg/min). Normal rats: After oral administration of glimepiride (0.1 mg/kg/day; NG) or saline (NC) for 2 weeks, euglycemic clamp procedures were performed. During submaximal hyperinsulinemia (620 +/- 35 pmol/l, mean +/- S.E.M.), metabolic clearance rates of glucose (MCR) in NG were significantly higher than in NC (25.1 +/- 2.1 vs. 18.3 +/- 1.2 ml/kg/min, P < 0.05). During maximal hyperinsulinemia (5235 +/- 270 pmol/l), MCRs in NG were higher than in NC, but there was no statistical significance (43.3 +/- 2.8 and 38.9 +/- 2.8). Diabetic rats: streptozotocin-induced diabetic rats were divided into four groups, GI (glimepiride treatment, 0.1 mg/kg/day p.o., with insulin, 5 U/day s.c.), SI (insulin alone), SG (glimepiride alone), and SC (saline). MCRs in the four groups were similar during 6 mU/kg/min clamps. During 30 mU/kg/min clamps, MCRs in GI were significantly higher than those in SC, SG or SI (23.4 +/- 2.8 vs. 12.2 +/- 1.9 and 8.9 +/- 0.8, P < 0.01, and vs. 17.4 +/- 1.5, P < 0.05). Although MCRs in SI tended to be higher than in SC, there was no significant statistical difference between these two groups. These results suggest that glimepiride enhances insulin action in peripheral tissues, and that glimepiride treatment with insulin improves the insulin resistance observed in streptozotocin-induced diabetic rats.

Administration, Oral↗
PubMedDate not supplied

Biguanides may produce hypoglycemic action in isolated rat hepatocytes through their effects on L-alanine transport.

We investigated the mechanisms of the effects of the biguanides metformin and buformin on hepatic gluconeogenesis in hepatocytes isolated from normal rats. Both 10 nM glucagon and 50 microM dibutyryl cAMP increased [3H]alanine uptake in isolated hepatocytes of normal rats by about 150% and 55%, respectively, compared with the effect of 5 mM alanine alone. Metformin (3 mM) reduced glucagon-stimulated [3H]alanine uptake to the level seen with alanine alone; buformin (3 mM) inhibited glucagon-stimulated [3H]alanine uptake by about 69%. The effects of biguanides on dibutyryl cAMP-stimulated [3H]alanine uptake were similar, but of smaller magnitude compared with those observed in the presence of glucagon. Ouabain (3 mM) had a stronger inhibitory effect on [3H]alanine uptake than the biguanides. However, 3 mM tolbutamide failed to suppress [3H]alanine uptake in the presence or absence of glucagon or dibutyryl cAMP. Our results suggest that the inhibition of alanine uptake, related to a reduction in the Na+/L-alanine transport system, is a possible mechanism of biguanide-related inhibition of hepatic gluconeogenesis.

Alanine↗
PubMedDate not supplied

Niceritrol prevents the decrease in red blood cell 2,3-diphosphoglycerate and neuropathy in streptozotocin-induced diabetic rats.

Nerve ischemia/hypoxia has been linked to the pathogenesis of diabetic complications. Red blood cell 2,3-diphosphoglycerate is an important regulator of peripheral tissue oxygenation; however, the relationship between 2,3-diphosphoglycerate concentration and diabetic complications has not been studied in detail. This investigation focused on the relationship between red blood cell 2,3-diphosphoglycerate and diabetic neuropathy, by measuring motor nerve conduction velocity and sciatic nerve blood flow in streptozotocin-induced diabetic rats. The effect of treatment with niceritrol, a nicotinic acid derivative that acts as a vasodilator and reduces serum lipid concentrations, on 2,3-diphosphoglycerate concentration and diabetic neuropathy was also examined. Untreated diabetic rats had significantly lower concentrations of red blood cell 2,3-diphosphoglycerate, higher concentrations of serum total cholesterol and triglyceride, as well as reduced motor nerve conduction velocity and sciatic nerve blood flow, compared to untreated normal rats. Niceritrol prevented these abnormalities without correcting hyperglycemia in diabetic rats, but had no effect on these parameters in normal rats. Red blood cell 2,3-diphosphoglycerate concentration and motor nerve conduction velocity showed a positive correlation with sciatic nerve blood flow and 2,3-diphosphoglycerate, respectively. These observations suggest that ischemia/hypoxia plays an important role in the development of diabetic neuropathy, and that niceritrol has a therapeutic effect on this condition by improving endoneurial ischemia/hypoxia.

2,3-Diphosphoglycerate↗
PubMedDate not supplied

Clinical investigation of epalrestat, an aldose reductase inhibitor, on diabetic neuropathy in Japan: multicenter study. Diabetic Neuropathy Study Group in Japan.

A number of diabetic patients with diabetic neuropathy were treated with epalrestat, an aldose reductase inhibitor, since this drug was launched into the market in Japan. More than 5000 patients with diabetic neuropathy who were treated with epalrestat for 3-12 months were treated to analyze the efficacy and the adverse reactions of the drug in this study. The improvement rates of subjective symptoms (i.e., spontaneous pain, numbness, coldness, and hypoesthesia) was 75% (slightly improved or better) and those of nerve function tests (i.e., motor nerve conduction velocity, sensory nerve-conduction velocity, and vibration threshold) 36%. Adverse drug reactions were encountered in 129 cases (2.5%) out of 5249 patients, none of which were severe ones. Although data are limited, they strongly suggest that epalrestat is a highly effective and safe agent for the treatment of diabetic neuropathy.

Adult↗
PubMedDate not supplied

Intra-articular osteochondroma of the ankle joint.

Intra-articular osteochondroma is a rare entity that appears as a single giant osteocartilaginous loose body in a joint cavity. The few reported cases of intra-articular osteochondroma have occurred in the knee joint. We report the case of a large osteochondral loose body in the ankle joint of a 10-year old girl and discuss the origin of the osteochondral tumor.

Ankle Joint↗
PubMedDate not supplied

Synthesis and anticoagulant activity of sulfated glucoside-bearing polymer.

Poly(glucosyloxyethyl methacrylate) sulfate [poly(GEMA) sulfate], which contains sulfated glucoside residues, was prepared by the reaction with N,N-dimethylformamide (DMF)/sulfur trioxide (SO3) complex. The degree of sulfation was easily controlled by changing the amount of DMF/SO3 complex added and reaction time. The total human blood clotting time in the presence of poly(GEMA) sulfate was prolonged by increasing the dose or the degree of sulfation of the polymer. The anticoagulant activity of poly(GEMA) sulfate was also compared with that of dextran sulfate, poly(styrenesulfonic acid), poly(vinylsulfuric acid), and heparin. The result suggests that sulfated saccharide residues are essential for endowing anticoagulant activity to synthetic polymer.

Anticoagulants↗
PubMedDate not supplied

Direct observation of fibrinogen-heparinoid complexes formation using surface plasmon resonance.

We analyzed the binding of heparinoid or heparin with fibrinogen by real-time measurement using surface plasmon resonance technology. Poly(glucosyloxyethyl methacrylate) sulfate [poly(GEMA) sulfate] and dextran sulfate were used as heparinoids. The binding ability of each sulfated polymer was estimated by having each polymer-containing buffer interact with the sensor chip surfaces that had immobilized fibrinogen. Dextran sulfate and poly(GEMA) sulfate showed high affinity to the fibrinogen in this experiment, while the heparin did not. All of the dextran sulfates were desorbed from its surface, while about 30% of the poly(GEMA) sulfate remained on the immobilized fibrinogen upon the addition of NaCl to the buffer which was done in order to analyze the desorption of poly(GEMA) sulfate or dextran sulfate from the surface of the fibrinogen. These data show that the type of binding between fibrinogen-poly(GEMA) sulfate was different from that of dextran sulfate, indicating that the interaction between fibrinogen and poly(GEMA) sulfate was caused not only by an electrostatic but also by a hydrophobic force. These results suggest that the interaction mechanism of heparinoids with fibrinogen was different from that of heparin.

Biopolymers↗
PubMedDate not supplied

Fibromuscular dysplasia complicated by primary thrombocythemia presenting recurrent ischemic cerebrovascular accidents: a case report.

A patient with fibromuscular dysplasia associated with primary thrombocythemia is reported. The patient, a 46-year-old female, had recurrent episodes of ischemic cerebrovascular accidents. Cranial CT scans revealed multiple low density areas in the right frontal and parietal lobes, and cerebral angiograms showed evidence of multiple embolisms. In addition, occlusion of the right internal carotid artery developed. To our knowledge, this is the first report on fibromuscular dysplasia complicated by essential thrombocythemia. The pathogenesis of the severe thrombotic tendency is discussed.

Angiography, Digital Subtraction↗
PubMedDate not supplied

Pharmacological action of YM737, a new glutathione analogue, in rats with experimental hematoma.

The effects of YM737, a glutathione analogue, and glutathione on neurological deficits and cerebral malondialdehyde concentrations were investigated in rats with experimental hematoma. A unilateral cerebral hematoma was provoked by injecting 0.25 ml of autologous blood around the capsula interna, putamen and caudate nucleus of the left cerebral hemisphere of the rat. Drugs were administered daily for four days beginning immediately after the operation. Neurological deficits and cerebral malondialdehyde concentrations were measured daily for 4 days. In the vehicle-treated group, deficits reached a maximum on the second day after the operation and then gradually recovered. YM737 (300 mg/kg, i.p.) accelerated recovery from neurological deficits, while glutathione had no effect. YM737 (300 mg/kg, i.p., on the fourth day after the operation) reduced the increase in malondialdehyde concentrations. Our results suggest that YM737 improves neurological deficits in this cerebral hematoma model, presumably partly due to inhibition of the lipid peroxidase response.

Animals↗
PubMedDate not supplied

Pharmacological studies on the hypoglycemic effect of 7,8-dihydro-2-(4-methylpiperazinyl)-4-(1-pyrrolidinyl)-6H-thi opyrano [3,2-d] pyrimidine dimaleate (MTP-1307), a novel hypoglycemic agent.

MTP-1307, 7,8-dihydro-2-(4-methylpiperazinyl)-4-(1-pyrrolidinyl)-6H- thiopyrano[3,2-d]pyrimidine dimaleate, is a novel oral hypoglycemic agent, structurally different from any existing hypoglycemic drugs. In fasted rats, the hypoglycemic effect of MTP-1307 was accompanied by elevation of the plasma insulin. In glucose tolerance tests, MTP-1307 suppressed the hyperglycemia after glucose loading and significantly enhanced the glucose-induced insulin secretion. In isolated hepatocytes from fasted rats, MTP-1307 inhibited gluconeogenesis from lactate and alanine. Furthermore, MTP-1307 increased the lactate/pyruvate ratio but did not increase the lactate level. MTP-1307 did not influence glycogenolysis in isolated hepatocytes from fed rats. In genetically diabetic ob/ob mice, MTP-1307 decreased the blood glucose level and improved glucose tolerance, but did not affect the level of plasma insulin. MTP-1307 increased 14CO2 production from glucose in isolated epididymal fat pads of ob/ob mice. Thus, these findings suggest that MTP-1307 produces hypoglycemic activities not only in normal animals but also in genetically diabetic animals, and that the hypoglycemic mechanism of MTP-1307 involves the promotion of glucose utilization in adipose tissue and, partially, the inhibition of gluconeogenesis in the liver and the stimulation of insulin release from the pancreas.

Adipose Tissue↗
PubMedDate not supplied

Use of the C64 quantitative tuning fork and the effect of niceritrol in diabetic neuropathy.

We investigated the usefulness of the C64 quantitative tuning fork in assessing vibratory sensation in patients with diabetic neuropathy. The vibratory sensation scores determined by using the C64 quantitative tuning fork were significantly correlated with severity of subjective symptoms of numbness, cold, desensitization, spontaneous pain in the upper and lower extremities, and vertigo, as well as measurements of neurologic function (threshold of vibratory sensation, the coefficients of variation of the R-R intervals of the electrocardiogram at rest, and the motor nerve conduction velocity [MNCV] of the lower extremities; P < 0.05 to 0.01). Subsequently, we evaluated the effects of niceritrol on neurologic function in the same patients by using the C64 quantitative tuning fork, other neurologic function tests, and the change in severity of subjective symptoms before and after therapy. Niceritrol significantly improved measures of neurologic function (vibratory sensation scores, MNCV of the upper extremities, and sensory nerve conduction velocity of the lower extremities; P < 0.05 to 0.001), and subjective symptoms (numbness, cold, desensitization, and spontaneous pain in the lower extremities; P < 0.01 to 0.001). Our results suggest that the C64 quantitative tuning fork is a convenient and objective tool for assessing the severity of diabetic neuropathy and that niceritrol is useful for the treatment of this disease.

Blood Glucose↗