Search PubMed⌕ Search

Biomedical subjects

N Sakamoto

Publications and source records attributed to N Sakamoto.

At least 253 records · Page 14Linked to original sources
PubMed1992

Correlation between the expression of P-glycoprotein and multidrug-resistant phenotype in transitional cell carcinoma of the urinary tract.

The expression of a multidrug-resistant (MDR) gene product, P-glycoprotein, was examined immunohistochemically in 41 transitional cell carcinomas (TCCs) of the urinary tract. In 23 of these, chemosensitivity to adriamycin (ADM) and vinblastine (VBL) was also assessed by a microtiter succinate dehydrogenase inhibition test and the correlation between the expression of P-glycoprotein and MDR phenotype was investigated. P-glycoprotein was detected in 13 (72.2%) of the 18 untreated TCCs of the upper urinary tract (UUT), 6 (31.6%) of the 19 untreated TCCs of the bladder, and all of the 4 TCCs treated with M-VAC chemotherapy, respectively. Fourteen (87.5%) of the 16 TCCs with a positive expression of P-glycoprotein were resistant to ADM and VBL, whereas all of the 4 TCCs sensitive to both drugs were negative in the expression of P-glycoprotein. The succinate dehydrogenase activity of TCCs with a positive expression of P-glycoprotein was significantly higher than that of TCCs with a negative expression of P-glycoprotein (P < 0.05). Thus, there was a good correlation between the expression of P-glycoprotein and MDR phenotype in the chemosensitivity test. These results suggest that intrinsic MDR exists in some TCCs of the urinary tract, particularly UUT, and that the immunohistochemical investigation of P-glycoprotein may be useful for predicting the MDR phenotype in TCCs of the urinary tract.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Bellini duct carcinoma of the kidney.

Human epithelial cells of the kidney present a wide spectrum of cytological and histological variation. The normal epithelium of the kidneys also includes a number of morphologically and functionally different cell types which are arranged along the nephrons and collecting ducts. Although renal carcinoma can involve any type of renal cell, the most common is renal cell carcinoma of the proximal tubuli. Here, we present the case of a 65-year-old Japanese patient with a renal cell carcinoma arising from Bellini duct epithelial cells. State-of-the-art techniques were used to establish the diagnosis and histogenesis of this renal cell carcinoma.

Aged↗
PubMed1992

Effects of the protein phosphatase inhibitors okadaic acid and calyculin A on insulin release from rat pancreatic islets.

The role of protein phosphatases in the regulation of insulin release from rat pancreatic islets was studied with protein phosphatase inhibitors, okadaic acid and calyculin A. Okadaic acid inhibited glucose- and glyceraldehyde-induced insulin release dose-dependently and also inhibited the potentiation of glucose-induced release either by adding forskolin, an activator of adenylate cyclase or by increasing K+ concentration to 25 mM. At a non-stimulatory concentration of 3 mM glucose, a high concentration (2 microM) of okadaic acid inhibited insulin release induced by high K+ or 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, but a low concentration (1 microM) of okadaic acid did not significantly inhibit TPA-induced insulin release. Calyculin A also inhibited glucose-induced insulin release, and the effect was greater than that of okadaic acid. The data suggest that protein phosphatases may play an important role in the regulation of insulin release.

Animals↗
PubMed1992

Effect of niceritrol on streptozocin-induced diabetic neuropathy in rats.

Niceritrol, a drug with peripheral tissue vasodilatory and serum lipid-lowering activity, was administered for 2 mo to rats with streptozocin-induced diabetes. Physiological and biochemical studies were subsequently conducted on rat nerve tissue. A markedly lower value of approximately 47% in sciatic nerve blood flow (SNBF) was detected in an untreated diabetic (DC) group than in a nondiabetic control group (CC). A significant delay in caudal motor nerve conduction velocity (MNCV) and significantly higher glucose, sorbitol, and fructose values were observed in the sciatic nerve and serum lipids. In contrast, a niceritrol-treated diabetic (DN) group had significantly higher SNBF, MNCV, and sciatic nerve myo-inositol values and lower serum triglyceride levels than group DC. No differences between these two groups were noted in glucose, sorbitol, and fructose levels in the sciatic nerve, or in cholesterol and glucose in serum. These findings suggest that niceritrol has a clear inhibitory effect on the development of delayed MNCV in the diabetic rat, which may be due to reduced nerve blood flow and/or decreased nerve myo-inositol levels.

Animals↗
PubMed1992

[Recurrence following surgery for primary renal pelvic and ureter cancer--clinicopathologic analysis of distant metastasis].

A retrospective analysis of 59 patients with renal pelvic and ureter cancer (56 transitional cell carcinomas, 2 squamous cell carcinomas, and 1 adenocarcinoma), which were treated surgically, was performed in relation to postoperative recurrence, particularly distant metastasis. Of the 59 cases, postoperative recurrences developed as distant metastasis in 9 cases (15.3%), as bladder cancer in 19 cases (32.2%) and as contralateral renal pelvic and ureter cancer (bilateral metachronous cancer) in 3 cases (5.1%). Three of the 9 cases with the development of distant metastasis were squamous cell carcinoma or adenocarcinoma, and the others transitional cell carcinoma. All the metastases occurred within 2 years. In cases with transitional cell carcinoma, nonpapillary tumor, grade 3, high stage (pT3 and pT4), positive vascular invasion and IFN beta or gamma had a significant influence on the rate of distant metastasis. On the other hand, location, diversity and previous or coexistent bladder cancer did not seem to be related to the frequency of the development of distant metastasis. Thus, tumor aggressiveness was the only predictive valuable of the development of distant metastasis after surgery for renal pelvic and ureter cancer.

Adenocarcinoma↗
PubMed1992

Effects of a new immunosuppressive agent, FK506, in rats with active Heymann nephritis.

FK506 is a recently-developed immunosuppressive drug. The aim of the present work was to investigate the effects of FK506 in experimental autoimmune glomerulonephritis (active Heymann nephritis) in rats. Active Heymann nephritis was induced in female Lewis rats by two immunizations with the homologous brush border vesicles (BBVs) at day 0 and day 28 (groups I, II, V, and VI). Rats of groups III and IV received the third immunization at day 56. In rats of groups I and III, FK506 was injected (1 mg/kg/day IM) from day 0 for 14 days. In rats of groups II and IV, significant proteinuria was observed (group II, 112.8 mg/16 hours; group IV, 55.4 mg/16 hours) at the time the rats were killed (day 84). Coarse subepithelial immune deposits (IDs) were found in these rats. In contrast, urinary protein excretion remained within normal range (less than 3.0 mg/16 hours) in groups I and III rats, and tiny subepithelial IDs were only occasionally seen. Circulating anti-BBV antibody levels were markedly lower in group I and III rats than in those of groups II and IV during the period between day 14 and day 56. To investigate the effects of FK506 on the proteinuric rats, FK506 (1 mg/kg/day, IM) was administered every day for 2 weeks beginning on day 56 (group V).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Pharmacokinetics and clinical effect of recombinant human erythropoietin on the anemia of predialysis patients].

The marvelous effect of recombinant human erythropoietin (EPOCH) on the anemia of the patients suffering from chronic renal failure had been already reported even in the predialysis patients. However, the influence on residual renal function as well as pharmacokinetics of EPOCH in predialysis patients was not clarified yet. Therefore, we made a clinical study of EPOCH in 10 predialysis patients to investigate the clinical effect as well as pharmacokinetics. EPOCH was administered intravenously once a week with the dosage of 3,000-9,000 IU for 8 weeks. All patients showed prominent improvement of anemia. Though no patient show serious adverse effect, two patients showed controllable hypertension accompanying with the increase of hematocrit. Meanwhile, the speed of the deterioration of residual renal function obtained from the regression line by reciprocal of the serum creatinine was not aggravated by the correction of anemia. Pharmacokinetic study revealed that the halflife of EPOCH was extended compared to normal but the degree of extension was same as that of in dialyzed patients. The plasma concentration-time curves showed the pattern of monoexponential disappearance and the area under the curve (AUC 0 to 48 hr.) showed dose-response increase. However, both parameters mentioned above as well as systemic clearance rate did not show any change between those of on day 0 and on day 56. These results no long-term accumulation of EPOCH, though the level of intrinsic erythropoietin was decreased after EPOCH treatment. Thus, the beneficial effect of EPOCH on the correction of anemia was revealed even in the predialysis patients without affecting on residual renal function.

Adult↗
PubMed1992

Three stages of copper accumulation in hepatocellular lysosomes: X-ray microanalysis of copper-loaded golden hamsters.

Male golden hamsters were loaded with copper by supplying them for up to 12 weeks with drinking water containing 0.5% cupric acetate. The copper feeding increased hepatic copper to widely varying levels. Energy dispersive X-ray microanalysis could always identify a copper-sulphur complex in the hepatocyte lysosomes of copper-loaded hamsters and the X-ray intensity of copper was found to be a reliable parameter to measure in-situ copper accumulation. Combining this parameter with the copper binding ratio expressed by delta Cu/delta S enabled us to discern two stages of sub-histochemical copper accumulation. The first stage was marked by low levels of both lysosomal copper and binding ratio, which suggested that this initial copper transfer was mediated by unsaturated cuproproteins. The second stage was characterized by median amounts of lysosomal copper and a binding ratio of more than 0.50. At the third stage, histochemically detectable copper appeared in animals whose lysosomal copper was extraordinarily high in later experimental periods. With the copper binding ratio being in the same range of 0.50-0.83, it seemed that saturated cuproproteins were the main mediator of copper transport in the later two stages.

Animals↗
PubMed1991

Inhibition of angiogenesis and tumor growth by a synthetic laminin peptide, CDPGYIGSR-NH2.

A laminin-derived synthetic peptide, Cys-Asp-Pro-Gly-Tyr-Ile-Gly-Ser-Arg-NH2 (CDPGYIGSR-H2), containing an active site for cell binding inhibited both angiogenesis and solid tumor growth. It potently suppressed both embryonic angiogenesis of the chick chorioallantoic membrane and migration of vascular endothelial cells induced by a tumor-conditioned medium but neither the in vitro proliferation of endothelial cells nor that of tumor cells. Additionally, in in vivo tests, CDPGYIGSR-NH2 markedly inhibited both the growth of s.c. solid tumor of Sarcoma 180 and that of Lewis lung carcinoma (3LL) in the lungs. On the contrary, ascitic tumor growth of Sarcoma 180 was not affected by this peptide, even though the same cell source was used. It was concluded that solid tumor growth inhibition by CDPGYIGSR-NH2 was due not a direct effect on cell growth but to antiangiogenic effect mediated by the inhibition of endothelial cell migration.

Animals↗
PubMed1991

Genomic organization of the alpha chain of the human C4b-binding protein gene.

C4b-binding protein (C4bp) is a serum glycoprotein that is one of the regulators of the complement activation (RCA) family. This protein is composed of structurally related 70-kDa (alpha chain) and 45-kDa (beta chain) polypeptides. The alpha chain of C4bp (C4bp alpha) consists of eight short consensus repeats (SCR), which constitute the amino-terminal 491 residues. Human C4bp is also one of the acute-phase reactants. In order to clarify the genetic basis of the SCR and to understand the regulatory mechanisms of C4bp synthesis, we isolated 6 genomic DNA clones covering all of the human C4bp alpha gene. This gene consists of 12 exons and spans about 40 kb. Each of the SCRs is encoded by a single exon, except for the second SCR (SCR II), which is encoded by two separate exons, demonstrating that human C4bp alpha has a split SCR at the genomic level. The 5' flanking region was sequenced up to 380 bases upstream from the putative transcription initiation site. Several possible binding sites for transcription factors were identified.

Base Sequence↗
PubMed1991

Evaluation of the densitometric method of ejection fraction by direct digital subtraction left ventriculography.

The aim of the present study was to test the hypothesis that the densitometric ejection fraction (EF) could be calculated by direct contrast digital subtraction left ventriculography in a single heartbeat. Thirty patients underwent direct contrast digital subtraction left ventriculography and biplane conventional left ventriculography. The values of EF were obtained from digital subtraction ventriculograms of the first cardiac cycle after completion of the injection of the contrast medium by the videodensitometric technique and were compared with those obtained from conventional ventriculograms by the area-length method in the same patients. There was a close correlation between the densitometric EF from digital subtraction ventriculograms and the volumetric EF from conventional ventriculograms (r = 0.78). Densitometric EF measured in the 30 degree right anterior oblique projection highly correlated with densitometric EF measured in the 60 degree left anterior projection (r = 0.98). These data suggest that this densitometric technique is available in any projection and is a simple procedure for the accurate measurement of left ventricular EF.

Absorptiometry, Photon↗
PubMed1991

Experimental bacterial prostatitis in rats.

Experimental acute bacterial prostatitis in rats was induced by four different routes of bacterial inoculation. The most simple and reproducible method of producing bacterial prostatitis was to instil the bacterial suspension into the prostatic urethra after the administration of an appropriate antibiotic to prevent associated pyelonephritis.

Amikacin↗
PubMed1991

Reciprocal changes of plasma glucose and ketone bodies in fasted and acutely diabetic rats after CNS stimulation.

To assess the effect of chemical stimulation of the central nervous system (CNS) on ketogenesis, we injected neostigmine (5 x 10(-8)mol) into the third cerebral ventricle in normal rats fasted for 48 h and fed rats with diabetes induced by streptozotocin (STZ, 80 mg/kg). The hepatic venous plasma levels of ketone bodies (3-hydroxybutyrate and acetoacetate), free fatty acids (FFA), and glucose were measured for 120 min after the injection of neostigmine under pentobarbital anesthesia. In the normal rats, plasma glucose levels were significantly increased but neither ketone bodies nor FFA were affected by CNS stimulation with neostigmine. In contrast the plasma levels of ketone bodies and FFA were significantly increased in STZ-diabetic rats, while glucose levels remained unchanged. The intravenous infusion of somatostatin (1.0 microgram/kg/min) suppressed the increase in plasma ketone bodies following CNS stimulation in STZ-diabetic rats. These findings suggest that CNS stimulation with neostigmine may accelerate ketogenesis by promoting the lipolysis, which may be induced by glucagon, in fed diabetic rats but not in normal fasted rats.

Animals↗
PubMed1991

Hyperglycemia induced by hippocampal administration of neostigmine is suppressed by intrahypothalamic atropine.

We investigated the relationship between the hyperglycemia induced by the administration of neostigmine into the hippocampus and the hypothalamus. Prior to the injection of neostigmine (5 x 10(-8) mol) into the hippocampus, 1 microliter each of atropine or hexamethonium (5 x 10(-11)-5 x 10(-8) mol) was injected into the bilateral ventromedial hypothalamus (VMH). Atropine suppressed in a dose-dependent manner the hyperglycemia induced by hippocampal administration of neostigmine, whereas hexamethonium had no significant effect. These observations suggest that the pathway for this experimental hyperglycemia involves, at least in part, the muscarinic cholinergic neurons in the VMH.

Animals↗
PubMed1991

Relative contribution of nervous system and hormones to CNS-mediated hyperglycemia is determined by the neurochemical specificity in the brain.

To determine whether CNS regulatory pathways are organized so that differential sympathetic outflow patterns occur in response to stress, we injected various doses of neostigmine or bombesin into the third cerebral ventricle of fed rats, and then measured the hepatic venous plasma concentrations of glucose, glucagon, insulin, and epinephrine. The following four groups of rats were studied. Group 1 was intact rats. Group 2 comprised intact rats receiving the constant infusion of a) somatostatin to inhibit the endogenous secretion of insulin and glucagon, and b) insulin to maintain the plasma insulin concentration at basal levels. The infusion was started from -30 minutes and given via a catheter in the femoral vein. Group 3 consisted of rats that underwent bilateral adrenal medullectomy (ADMX) one week before the experiment. Group 4 was ADMX rats administered a constant infusion of somatostain with insulin through a femoral vein, as above. The administration of 1 x 10(-9) mol neostigmine caused hepatic venous hyperglycemia mediated by three distinct pathways: 1) direct innervation of the liver, 2) a direct action of epinephrine on the liver, and 3) the action of glucagon on the liver. We estimated the relative contribution of these three factors to be about 47, 32, and 21%, respectively. Relative contributions of three factors of the doses of 5 x 10(-9) and 5 x 10(-8) mol neostigmine demonstrated an effect similar to that of 1 x 10(-9) mol neostigmine. Epinephrine was shown to be the only agent involved in the hyperglycemic response to intraventricular bombesin at doses of 1 x 10(-10), 1 x 10(-9), and 1 x 10(-8) mol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗