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Biomedical subjects

N Sakamoto

Publications and source records attributed to N Sakamoto.

At least 217 records · Page 12Linked to original sources
PubMed1993

Development of the Overlapping Oligonucleotide Database and its application to signal sequence search of the human genome.

We have developed ODS (Overlapping Oligonucleotide Database for Signal Sequence Search)--the first relational database that integrates information on biological features into the search for signal sequences. In existing biological sequence databases, even relational ones, retrieving nucleotide sequences based on their biological features involves much labour and time or even the development of a new program. GenBank sequence data, including FEATURES records, are organized into three relational tables in ODS. Nucleotide sequences are transformed into overlapping oligonucleotides in order to facilitate the signal sequence search rapidly without the need for specific alignment programs. This transformation leads to a one-to-one correspondence between the nucleotide sequence and its biological feature. The signal sequence search by ODS is done in SQL queries and ODS obviates the need for molecular biologists to write computer programs. The application of ODS to searches of promoter regions revealed putative cis-acting elements and basic statistical analyses of occurrences of oligonucleotides showed interesting findings concerning the 'cg' dinucleotide.

Computer Systems↗
PubMed1993

Circadian blood pressure variation in diabetic patients with autonomic neuropathy.

OBJECTIVE: To elucidate distinctive patterns of circadian variation of blood pressure in diabetic patients. DESIGN: Circadian variations and indices of blood pressure variability were examined by non-invasive ambulatory blood pressure monitoring. The indices were assessed for a correlation with various possible signs of autonomic neuropathy, including the coefficient of variation of the RR interval and orthostatic hypotension. METHODS: The study was conducted on 38 normotensive diabetics and 15 age- and sex-matched non-diabetic controls, all of whom were outpatients at the Third Department of Internal Medicine in Nagoya University Hospital. Ambulatory blood pressure measurements were taken in all subjects and the coefficients of variation in the RR interval and postural changes in blood pressure were determined. RESULTS: The diabetic patients demonstrated a different pattern of circadian variation in blood pressure from that of the non-diabetics. Diurnal-nocturnal differences were significantly smaller in diabetics than in non-diabetic controls. Statistically significant correlations were found between diurnal-nocturnal differences in blood pressure and the duration of diabetes, glycaemic control, the coefficient of variation in the RR interval and the change in blood pressure on standing. A subgroup of diabetic patients with severe autonomic neuropathy showed the lowest diurnal-nocturnal differences. CONCLUSIONS: In diabetic patients with autonomic neuropathy circadian variations in blood pressure are blunted. Ambulatory blood pressure monitoring can detect these abnormal variations and therefore may be useful in evaluating diabetic autonomic neuropathy.

Adult↗
PubMed1993

Long-term effect of acarbose on glycaemic control in non-insulin-dependent diabetes mellitus: a placebo-controlled double-blind study.

The efficacy and safety of acarbose therapy (100 mg tds for 24 weeks) was investigated in a placebo-controlled double-blind study in patients with non-insulin dependent diabetes mellitus who could not achieve satisfactory glycaemic control by diet alone. In the acarbose group, the 2 h postprandial blood glucose and haemoglobin A1 levels decreased significantly from 14.0 mmol l-1 to 11.3 mmol l-1 and from 11.1% to 9.7%, respectively. In the placebo group, the 2 h postprandial blood glucose (14.4 mmol l-1 to 14.2 mmol l-1) and the hemoglobin A1 level (10.3% to 9.9%) showed no significant changes. A 75 g oral glucose tolerance test was performed before and after the study, the difference not being significant in either the acarbose group or the placebo group. The incidence of side-effects (mainly gastrointestinal symptoms such as flatulence and abdominal distension) was high at 78.9% in the acarbose group and 61.1% in the placebo group. However, there was no significant difference between the groups, and side-effects in the acarbose group tapered during the trial, suggesting that some at least were not related to the drug. From these findings, it was concluded that acarbose is an effective new treatment for diet treated non-insulin-dependent diabetic patients.

Acarbose↗
PubMed1993

The effect of acarbose on blood glucose profiles of type 2 diabetic patients receiving insulin therapy.

Nine patients with Type 2 diabetes receiving insulin therapy were treated with acarbose 100 mg thrice daily for 1 week to investigate the effect of acarbose on blood glucose control. Daily blood glucose profiles contained fewer excursions during acarbose administration and low levels were maintained. The M-value, an indicator of blood glucose fluctuation, decreased significantly from a run-in period value of 37.6 +/- 8.7 (SEM) to 16.7 +/- 4.0 during the acarbose period (p < 0.05) and rose again to 28.9 +/- 6.7 (p > or = 0.05) in the follow-up period. The 24-h urinary glucose excretion similarly decreased during acarbose administration. As expected, no decrease in HbA1C was observed due to the short treatment period. The 24-h urinary C-peptide excretions and serum lipids were not influenced by acarbose therapy. Frequent episodes of clinical hypoglycaemia were experienced while on acarbose therapy, indicating a decrease in insulin requirements. Adverse events such as flatulence and abdominal distention were observed in six out of nine cases. Symptoms were generally mild and well tolerated, only one patient dropped out because of diarrhoea and abdominal pain. We conclude that acarbose could usefully be administered to Type 2 diabetic patients treated with insulin to improve blood glucose control and reduce insulin requirement if the appropriate selection criteria were met.

Acarbose↗
PubMed1993

Effects of prolonged application of isoprenaline on intracellular free magnesium concentration in isolated heart of rat.

1. The effect of prolonged application of isoprenaline on intracellular free-Mg2+ concentration ([Mg2+]i) was examined by use of 31P-nuclear magnetic resonance (31P-n.m.r.) in rat isolated hearts. Left ventricular pressure (LVP) was simultaneously measured. 2. [Mg2+]i was estimated from the separation of the alpha- and beta-ATP peaks, using the dissociation constant of MgATP 38 microM (established previously). In normal (phosphate-free, Krebs-Henseleit) solution, [Mg2+]i was approximately 0.4 mM. 3. When isoprenaline was applied for 100 min, a transient increase in [Mg2+]i was observed during the initial 25 min, whilst concentrations of ATP ([ATP]) and phosphocreatine ([PCr]) decreased and [Pi] correspondingly increased. During the subsequent 75 min of isoprenaline application, [Mg2+]i decreased below its resting levels. Washout of isoprenaline restored [Mg2+]i and [PCr], but [ATP] remained low. These changes elicited by isoprenaline were not observed in the presence of propranolol, a typical alpha-adrenoceptor blocker. 4. Isoprenaline increased both LVP and heart rate. The increased LVP and heart rate slowly returned to lower values during prolonged application of isoprenaline, but remained higher than those before application. 5. The transient rise in [Mg2+]i elicited by isoprenaline could be attributed to the decrease in [ATP] resulting in a release of Mg2+. The subsequent decrease in [Mg2+]i during the prolonged applications suggests that beta-adrenoceptor stimulation itself facilitates Mg(2+)-extruding mechanism(s).

Adenosine Triphosphate↗
PubMed1993

Involvement of central cholinergic muscarinic receptors and histamine H1 receptors in hyperglycemia induced by prostaglandin F2 alpha in rats.

We studied the effects of the histamine H1 receptor antagonists diphenhydramine and pyrilamine, the H2 receptor antagonist ranitidine and the muscarinic receptor antagonist atropine injected into the third cerebral ventricle on prostaglandin F2 alpha (PGF2 alpha)-induced hyperglycemia in anesthetized fed rats. The concomitant injection of diphenhydramine (1 x 10(-8), 5 x 10(-8) mol) with 50 micrograms PGF2 alpha significantly suppressed the increase in hepatic plasma glucose concentrations induced by PGF2 alpha. The concomitant injection of 1 x 10(-8) mol pyrilamine with 50 micrograms PGF2 alpha did not suppress the above-mentioned parameter, while 5 x 10(-8) mol pyrilamine significantly suppressed it. Diphenhydramine suppressed the PGF2 alpha-induced hyperglycemia to a greater extent than did pyrilamine. In contrast, concomitant injection of the H2 receptor antagonist ranitidine (1 x 10(-8), 5 x 10(-8) mol) did not suppress the hyperglycemia induced by PGF2 alpha. The concomitant injection of 5 x 10(-8) mol diphenhydramine or pyrilamine with 50 micrograms PGF2 alpha significantly suppressed the increase in plasma epinephrine induced by PGF2 alpha, but the same dose of ranitidine had no effect. The concomitant injection of atropine (5 x 10(-8), 5 x 10(-7) mol) with 50 micrograms PGF2 alpha significantly suppressed the increase in hepatic plasma glucose and epinephrine induced by PGF2 alpha. These findings demonstrate that PGF2 alpha-induced hyperglycemia is mediated by the muscarinic receptors of cholinoceptive neurons and in part by H1 receptors in the central nervous system.

Animals↗
PubMed1993

Correlation between ultrasonic appearance and histology of periprostatic tissue.

We compared preoperative echograms and postoperative histological specimens from 16 patients who had undergone radical prostatectomy or radical cystourethrectomy to evaluate the correlation between the so-called capsular echogram obtained on transrectal ultrasonography and histology of the prostatic capsule. The capsular echogram corresponded to the periprostatic fatty tissue in all cases. In 10 of the 16 cases lateral ruptures of the capsular echogram were observed. Histologically, these ruptures corresponded to fibrous bundles in 6 of the 10 cases and to neurovascular bundles located close to the prostatic tissue in the other 4 cases. Because the prostatic glands, prostatic capsule, blood vessels and nerve fibers complicated the structure on the lateral sides near the apex, the borders of the prostatic gland were indistinct on the echograms.

Aged↗
PubMed1993

Expression of P-glycoprotein and multidrug resistance in renal cell carcinoma.

The expression of the multidrug-resistance gene product, P-glycoprotein was examined immunohistochemically in 31 untreated human renal cell carcinomas. In 17 of these, chemosensitivity to Adriamycin and vinblastine was also assessed by a microtiter succinate dehydrogenase inhibition test and the correlation between the expression of P-glycoprotein and intrinsic multidrug resistance was investigated. P-glycoprotein was detected in 16 (51.6%) of the 31 carcinomas. In the chemosensitivity test, 14 (82.4%) of the 17 carcinomas were estimated to be resistant to both drugs (multidrug resistant; MDR). Eight (72.7%) of the 11 carcinomas with a positive expression of P-glycoprotein were MDR, and none of them were sensitive of both drugs. On the other hand, MDR carcinomas were not necessarily associated with the expression of P-glycoprotein. Eight (61.5%) of the 13 MDR carcinomas showed a positive expression of P-glycoprotein while the remaining 5 (38.5%) were negative. These results suggest that the expression of P-glycoprotein is an important factor responsible for the intrinsic MDR phenotype of renal cell carcinoma, however, there are probably other factors involved as well which have yet to be fully elucidated.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Point mutation in a family with hyperproinsulinemia detected by single stranded conformational polymorphism.

We previously described a case of familial hyperproinsulinemia, the fifth to be reported. In the present study we characterized the genetic defect carried by this family and demonstrated that it could be detected by polymerase chain reaction-single stranded conformational polymorphism. Since the serum proinsulin molecule from the propositus, a 63-yr-old Japanese man, was eluted on the same fraction of human proinsulin intermediate cleaved only at the B-C junction, we sequenced exon 3 of his insulin gene, including the C-A junction. A point mutation was discovered that changed codon 65 from arginine (CGT) to histidine (CAT) in one allele. This was the same point mutation as that described previously in three unrelated kindreds representing two races, consistent with the hypothesis that the dinucleotide sequence CpG may be a "hot spot" for mutations. Recently, developed polymerase chain reaction-single stranded conformational polymorphism proved useful in detecting this mutation in the family members. The daughter of the propositus and one of his two grandsons were also demonstrated to be heterozygous for this point mutation by this method.

Base Sequence↗
PubMed1993

Are diabetic hearts more resistant to ischemia/reperfusion injury?

The present study was designed to investigate the cardiac impairment during ischemia/reperfusion injury in rats with streptozotocin-induced diabetes vs controls. Male rats were divided into three groups: controls, one-week diabetic rats (1wDM) and four-week diabetic rats (4wDM). In the isolated working heart, left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and maximum positive and negative dP/dt were measured before ischemia and after 20 min of global ischemia followed by 30 min reperfusion. In the pre-ischemic state, hearts of 4wDM showed a significant (p < 0.05) depression of the maximum positive and negative dP/dt compared with those of controls and 1wDM. There were no significant differences in LVDP and LVEDP among the three groups. The incidence of reperfusion-induced ventricular fibrillation (VF) was 75% for controls, 15% for 1wDM rats, and 27% for 4wDM rats. In hearts without reperfusion-induced VF, there were no differences in the three groups, between the pre- and post-ischemic values in LVDP, LVEDP, and maximum positive and negative dP/dt. These findings suggest that diabetic hearts exhibit no susceptibility to ischemia/reperfusion injury.

Animals↗
PubMed1993

Cypridina luciferin analog reduces the incidence of ischemia/reperfusion-induced ventricular fibrillation.

A Cypridina luciferin analog (CLA), considered to be a sensitive and specific agent for the assay of superoxide, was assessed in isolated hearts for its effects on ischemia/reperfusion injury. Hearts of anesthetized male Wistar rats were isolated and perfused with a modified Krebs-Henseleit bicarbonate buffer to serve as non-recirculating working heart preparations. After 15 min of perfusion to achieve stability, they underwent 20 min of global ischemia and were then reperfused for 30 min with or without 250 microM of CLA, dissolved in the perfusate. The incidence of ventricular fibrillation was only 13% in the CLA group, whereas it was 88% in the controls. The CLA treatment was further associated with significantly increased left ventricular developed pressure and cardiac output; and in contrast, the left ventricular end-diastolic pressure was significantly reduced, as compared with the control group. Thiobarbiturate reacting substance content in the hearts of the CLA group was significantly decreased (27.5 +/- 2.4 versus 36.9 +/- 9.7 mumol/g dry weight). This study thus indicates that CLA may be useful for alleviating ischemia/reperfusion injury (reperfusion-induced arrhythmia and damage to heart function) involving free radicals.

Adenosine Triphosphate↗
PubMed1993

Effects of diabetes on lipid peroxidation and scavenger activity in ischemia/reperfusion injury.

This study examined the effects of ischemia/reperfusion on cardiac function and diabetes-associated lipid peroxidation and scavenger induction in isolated working hearts. Cardiac function in diabetic rats was depressed in proportion to the duration of diabetes. Plasma levels of malondialdehyde (MDA) were increased significantly after diabetes of 1-week duration (1wD). MDA levels in the myocardium were increased significantly after 4-weeks (4wD) and tissue superoxide dismutase (SOD) activity was also elevated significantly in 8-week diabetic rats (8wD) as compared to control values. In both controls and diabetics, tissue MDA concentrations increased significantly during the first 3 min of reperfusion following 20 min of ischemia, compared with preischemia levels. At the end of reperfusion, tissue MDA levels decreased in controls and 1wD hearts, but remained elevated in the 4wD and 8wD cases. The SOD activity in 8wD hearts decreased significantly after 20 min of global ischemia followed by 30 min reperfusion, compared with preischemia levels. By contrast, there were no significant differences between preischemic and after-reperfusion data for parameters of cardiac function in 8wD rats. Thus, lipid peroxidation appears to have little influence on cardiac function during ischemia/reperfusion in rats with chronic diabetes.

Animals↗
PubMed1993

Effects of high glucose concentrations and epalrestat on sorbitol and myo-inositol metabolism in cultured rabbit aortic smooth muscle cells.

To clarify the relationship between abnormality of sorbitol and/or myo-inositol metabolism caused by hyperglycemia and diabetic macroangiopathy, we investigated the effects of high glucose concentrations and epalrestat, an aldose reductase inhibitor, on the metabolism of sorbitol and myo-inositol in cultured rabbit aortic smooth muscle cells. In cells incubated in the presence of 30 mM glucose for 72 h, the sorbitol content increased approximately 4.5-fold, and the myo-inositol level decreased by 55% compared with control values. Kinetic analysis of high-affinity myo-inositol uptake suggested that smooth muscle cells exposed to high glucose concentrations exhibited a noncompetitive type of inhibition characterized by ouabain-sensitive, energy-dependent active transport. Epalrestat blocked glucose-induced changes in sorbitol and myo-inositol metabolism, suggesting that these changes were caused by the accumulation of sorbitol in the cells. These metabolic changes may impair function of smooth muscle cells, contributing to the pathology of diabetic atherosclerosis, especially Mönckeberg's calcific medial sclerosis. The use of an aldose reductase inhibitor may prevent these glucose-induced changes.

Aldehyde Reductase↗
PubMed1993

Pharmacokinetic study of recombinant human erythropoietin treatment in pre-dialysis end stage renal disease patients.

We treated pre-dialysis ESRD patients with recombinant human erythropoietin (rHuEPO) by either the subcutaneous (s.c.) or intravenous (i.v.) route, and investigated the pharmacokinetics of rHuEPO. Twenty patients were divided equally into two groups by the difference in route, and rHuEPO was administered once per week for 8 weeks. The dose was 3,000 and 6,000 IU in the s.c. group and 3,000, 6,000 and 9,000 IU in the i.v. group. Although anemia was corrected significantly in both groups, residual renal function was not affected significantly. Pharmacokinetic study revealed that none of the parameters changed between the initial and final treatments in any of the groups. Area under the curve (AUC) and maximum concentration (Cmax) was consistently smaller in the s.c. --than in the i.v.--treated group. Mean residence time (MRT) was 3 times longer in the s.c. group than in the i.v. group. Bioavailability of rHuEPO in the s.c. group was around 35%, and mean absorption time (MAT) was around 25 hours. Though the s.c. route has been reported to be more effective for correcting anemia with rHuEPO than the i.v. route when rHuEPO was administered either twice or three times per week, our study demonstrated that the effect of rHuEPO was almost equal between the s.c.-treated and i.v.-treated groups when rHuEPO was administered once per week. We assume that this equivalent degree of efficacy in the s.c. group in spite of low values of AUC and Cmax might be derived by the longer MRT. Thus, we consider that MRT is an important factor and the efficacy of rHuEPO should be investigated with evaluation of MRT when the administration route is different.

Adult↗
PubMed1993

Protective actions of YM737, a new glutathione analog, against cerebral ischemia in rats.

Effects of YM737[N-(N-r-L-glutamyl-L-cysteinyl)glycine 1-isopropyl ester sulfate monohydrate], a new glutathione (GSH) analog more readily transported into cells than GSH, on cerebral ischemia were compared with those of GSH and some other drugs in rats subjected to occlusion of the bilateral carotid arteries. YM737 significantly reduced lethality, increased brain-water levels as measured by both dry-wet and NMR methods, and increased malondialdehyde (MDA) levels in the cerebral ischemic rats. On the other hand, pharmacological actions of GSH itself was less than those of YM737. In the ischemic rats used in the present study, there was no significant difference in 31P-NMR signals between the normal and the cerebral ischemic rats. These results suggest that YM737 showed anti-cerebral ischemic effects presumably due, in part, to inhibition of lipid peroxidative responses.

Animals↗
PubMed1993

Hepatic copper accumulation in patients with primary biliary cirrhosis.

Liver biopsy specimens from 18 patients with primary biliary cirrhosis were examined histochemically and by energy-dispersive x-ray microanalysis. Using two indices, we classified hepatic copper accumulation into three stages based on the Cu x-ray intensity of cuproproteins that had accumulated in hepatocyte lysosomes and on the binding ratio of postulated copper transfer proteins between the cytosol and lysosomes. Eight patients were in stage 1 with an initial accumulation of lysosomal cuproproteins, mediated by transfer proteins not saturated with copper. Two patients were in stage 2, in which transfer proteins were saturated with copper. The first two stages gave negative results for histochemical copper. The remaining eight patients were in stage 3, in which copper accumulation detected by histochemical included transfer proteins saturated with copper and large amounts of lysosomal cuproproteins. Five patients (one each in stages 1 and 2, and three in stage 3) underwent a second liver biopsy after treatment with 600 mg of ursodeoxycholic acid daily for 14 to 39 months. Results of blood chemistry tests improved, but liver histologic findings and copper accumulation were unchanged in all five patients. It seems likely that ursodeoxycholic acid does not affect the copper accumulation in hepatocyte lysosomes that reflects the state of cholestasis in patients with primary biliary cirrhosis.

Adult↗