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Biomedical subjects

K Nagano

Publications and source records attributed to K Nagano.

At least 163 records · Page 9Linked to original sources

Regulation of Na+,K(+)-ATPases. I. Cloning and analysis of the 5'-flanking region of the rat NKAA2 gene encoding the alpha 2 subunit.

The nucleotide (nt) sequence of the genomic clone, spanning at least the first two exons of the rat Na+,K(+)-ATPase alpha 2 subunit-encoding gene and 6.5 kb of the 5'-flanking region, has been determined. S1 nuclease mapping analysis of the 5' end of the Na+,K(+)-ATPase mRNA indicated that the transcription start point (tsp) is located 105 bp upstream from the start codon. The tsp was identical among three adult-rat tissues (brain, skeletal muscle and heart) which produce the alpha 2 isoform. A TATA-like sequence was found 33 bp upstream from the tsp. In addition, multiple consensus binding sites for a wide variety of regulatory proteins were present throughout the upstream and downstream tsp-flanking regions. A remarkable conservation in the nt sequence of the 5'-flanking region was confirmed between the rat and human genes.

Animals↗

Regulation of Na+,K(+)-ATPase. II. Cloning and analysis of the 5'-flanking region of the rat NKAB2 gene encoding the beta 2 subunit.

We cloned a 14.5-kb fragment of genomic DNA spanning at least the first two exons of the rat Na+,K(+)-ATPase (EC 3.6.1.3) beta 2 subunit-encoding gene and 5.5 kb of the 5'-flanking region. The transcription start point (tsp) is located 595 bp upstream from the start codon. The tsp was identical for adult rat brain and spleen, both of which produce the beta 2 isoform. The TATA sequence was found 29 bp upstream from the tsp and Sp1-binding sites at nucleotides (nt) -55 and -147. In addition, multiple consensus binding sites for a wide variety of regulatory proteins were present throughout the upstream and downstream tsp-flanking regions. Conserved sequence elements which may serve for coordinated expression of the alpha and beta subunits were found in the nt sequence of the 5'-flanking region.

Animals↗

Effect of tumour necrosis factor in the mouse-tail model of psoriasis.

The effects of local and systemic administration of tumour necrosis factor (TNF) on the mouse-tail model of psoriasis were examined histologically at 4 days after administration. Subcutaneous injection of TNF at 1 x 10(1) to 1 x 10(4) units/mouse resulted in dose-dependent formation of a granular layer in the tail scales, which was quantified as the percentage of tail scales having granular layer formations extending over half or more of their surface and was larger than that occurring in untreated mice and in mice receiving injections of vehicle solution alone. Daily intraperitoneal injection of TNF at 1 x 10(3) or 1 x 10(4) units/mouse for 28 days resulted in similar granular layer formation and in a significantly reduced mitotic index of the tail keratinocytes, indicating an antiproliferative effect of TNF. The lowered mitotic index and the induction of granular layers, apparently attributable to a modulation of keratinocyte proliferation and differentiation by TNF, suggest that TNF may be effective as a drug for treatment of psoriasis.

Animals↗

Hepatic oxygen supply-uptake relationship and metabolism during anesthesia in miniature pigs.

The study evaluated the effects of different anesthetics on the hepatic oxygen supply-demand relationship and hepatic lactate uptake (HLu). Miniature pigs (n = 33), weighing 20-31 kg, were divided into five groups and accordingly anesthetized with halothane, isoflurane, enflurane (0.9%, 1.5%, and 2.2% end-expired concentrations, respectively), fentanyl (100 micrograms/kg iv bolus followed by a continuous infusion of 50 micrograms.kg-1.h-1), or sodium pentobarbital (30 mg/kg iv bolus followed by a continuous infusion at a rate of 1-2 mg.kg-1.h-1). The surgical preparation allowed the authors to induce a stepwise decrease in hepatic blood supply without congestion in the preportal tissues. Prior to induced hepatic hypoperfusion, the values of hepatic oxygen delivery (HDO2) were the greatest in the isoflurane and fentanyl groups and the smallest in the halothane group, while the values of hepatic oxygen uptake (HVO2) were the smallest in the halothane group without differences among the other four groups. During stepwise decrease in hepatic blood and oxygen supply, HLu started to decrease at higher values of hepatic oxygen delivery in the fentanyl group (HDO2 = 10 mlO2.min-1.100 g-1) than in all others (HDO2 = 6-7 mlO2.min-1.100 g-1). At values of HDO2 equal to 2-3 mlO2.min-1.100 g-1, the values of HLu became negative, signifying that the liver began to release rather than to metabolize lactate. There was a linear relationship between the values of HDO2 and hepatic venous oxygen tension or saturation (r = 0.96; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗

Protective effect of PGD2 against ethanol-induced gastric mucosal injury in rats.

The protective effect of prostaglandin D2 (PGD2) in ethanol-, HCl-, or NaCl-induced gastric mucosal injury was investigated. To clarify the mechanism, the gastric mucosal hemodynamics were also investigated using reflectance spectrophotometry and laser Doppler flowmetry in anesthetized rats. PGD2 administered orally significantly reduced the ethanol-induced mucosal injury. Although it did not reach any significance, PGD2 also reduced 0.6 N HCl-induced mucosal damage, and slightly reduced 25% NaCl-induced mucosal damage. Topical application of PGD2 did not affect gastric mucosal hemodynamics at steady state before the administration of necrotizing agent. However, PGD2 significantly improved the gastric mucosal microcirculatory congestion caused by ethanol, and partly improved 0.6 N HCl-induced ischemia. However, it did not improve the 25% NaCl-induced mucosal congestion. The results indicated that PGD2 had a protective effect in the ethanol-induced gastric mucosal injury through the improvement of gastric mucosal microcirculation. However, further investigations are needed to clarify the precise effect of PGD2 in 0.6 N HCl- or 25% NaCl-induced mucosal damage.

Animals↗

Hypothermia, hepatic oxygen supply-demand, and ischemia-reperfusion injury in pigs.

We examined the effects of two degrees of hypothermia on hepatic oxygen delivery and uptake, hepatic lactate uptake as a marker of hepatic function, and the effect of hypothermia on ischemia-reperfusion injury in the liver in miniature pigs (n = 18, 21-30 kg body wt). Hepatic arterial and portal venous blood flows were measured while hepatic oxygen delivery was progressively decreased without venous congestion in the preportal area. With decreases in hepatic blood and oxygen supply, oxygen extraction gradually increased from 50 to 90% in the normothermic group and from 25 to 70 and 84% in the hypothermic (30. and 34 degrees C, respectively) groups. The values of critical hepatic oxygen delivery were between 7.3 and 11.9 ml O2.min-1.100 g-1 without significant differences among the groups. During reperfusion after ischemic insult, hepatic oxygen uptake returned to base-line values in both hypothermic groups but remained substantially below base-line values in normothermic groups of animals. Hepatic enzyme concentrations (lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, and alcohol dehydrogenase) were substantially increased (up to 30-fold) in normothermic animals, but the concentrations did not increase in either of the hypothermic groups. These results demonstrated that hypothermia per se does not affect hepatic oxygen delivery but decreases hepatic oxygen demand and uptake, provides an effective protection from hepatic oxygen deprivation, and lessens reperfusion injury.

Animals↗

Hepatic circulation and oxygen supply-uptake relationships after hepatic ischemic insult during anesthesia with volatile anesthetics and fentanyl in miniature pigs.

The objective of the present study was to quantitate the effects of several anesthetics on hepatic circulation, oxygenation, and function after hepatic ischemic insult and during reperfusion. We examined the effects of different anesthetics on hepatic circulation, oxygenation, and function after hepatic ischemic insult in 28 miniature pigs weighing 20-27 kg. The preparation allowed a stepwise decrease followed by a complete cessation for 1 h of hepatic blood and oxygen supply. Immediately after the unclamping of both vessels supplying the liver and restoration of the hepatic circulation, systemic mean arterial pressure decreased to approximately 75% of preischemic values in animals anesthetized with pentobarbital and fentanyl and to 60% of preischemic values in pigs anesthetized with halothane, enflurane, or isoflurane. Total hepatic blood flow immediately returned to preischemic values without significant difference between the groups. Subsequently, hepatic oxygen delivery returned to 75%-95% of preischemic values. Hepatic oxygen uptake returned to 50%-60% of preischemic values in animals anesthetized with pentobarbital and with volatile anesthetics and up to 80% and then later to baseline values with fentanyl anesthesia. Lactate uptake by the liver returned to preischemic values only in animals given fentanyl or isoflurane but remained at approximately 50% of preischemic values during enflurane and 20%-40% during halothane and pentobarbital anesthesia. Thus, the study indicates that both isoflurane and fentanyl anesthesia provide more protection from ischemic insult than do halothane, enflurane, or pentobarbital anesthesia.

Anesthetics↗

Different effect of Helicobacter pylori on the human gastric antral and body mucosal intracellular mucin.

To elucidate the role of Helicobacter pylori infection in the pathogenesis of gastric ulcer, we investigated the intracellular mucin content by measuring the periodic acid-Schiff-Alcian blue (PAS-AB)-stained substances, by means of computer, in the biopsy sample of gastric mucosa from patients with and without H. pylori infection. In the antral mucosa the intracellular PAS-AB-stained mucin content was significantly smaller in patients with infection than in patients without infection, whereas in the oxyntic gland mucosa the intracellular mucin content showed no significant change between patients with and without infection. In an animal study we investigated the effect of ammonia, which might be produced by H. pylori in the presence of urea. The ammonia, administered orally, caused a greater decrease of intracellular PAS-AB-stained mucin content in the gastric antral mucosa than in the body mucosa, in a dose-dependent manner. The results suggested that H. pylori infection had a different effect on the gastric mucosal intracellular PAS-AB-stained mucin and lowered specifically the antral intracellular PAS-AB-stained mucin content, possibly due to generation of ammonia by H. pylori.

Alcian Blue↗

[Diffusion of ofloxacin (OFLX) into prostatic tissue in patients with benign prostatic hypertrophy].

Diffusion of ofloxacin (OFLX) into prostatic tissue was studied in 31 patients with benign prostatic hypertrophy. Concentrations of OFLX in the serum and prostatic tissue were measured at scheduled intervals after 200 mg OFLX oral administration. The mean OFLX level in prostatic tissue and tissue/serum ratio at 2 hours, 4 hours and 6 hours was 3.33 +/- 0.96 micrograms/g (1.25 +/- 0.28) in 10 patients, 2.21 +/- 0.55 micrograms/g (0.92 +/- 0.32) in 9 patients and 2.10 +/- 0.99 micrograms/g (1.01 +/- 0.23) in 12 patients, respectively. OFLX levels in prostatic tissue covered the minimum inhibitory concentration for several pathogenic bacteria detected from the infected prostatic fluid. Therefore, OFLX was thought to be a very useful drug for the treatment of bacterial prostatitis and postoperative infection of prostatic surgery.

Administration, Oral↗

[Clinical evaluation of ofloxacin in the treatment of chronic complicated urinary tract infection].

Ofloxacin was administered orally at a daily dosage of 300 mg and 600 mg in three divided doses for 14 days to 24 and 60 patients with chronic complicated urinary infections, respectively, in order to evaluate the therapeutic efficacy. The clinical efficacy was evaluated according to the criterion proposed by the UTI Committee in Japan and its efficacy was evaluated in 84 cases. In the group of 24 patients receiving a daily dosage of 300 mg, the clinical effectiveness after a 5-day treatment was excellent in 13 cases and moderate in 7 cases. The overall clinical efficacy was 83.8%. In the group of 60 patients receiving a daily dosage of 600 mg, the rate of overall clinical efficacy after a 5-day treatment was 83.3%, being excellent in 23 cases and moderate in 27 cases. The eradication rate was 85.3% and 92.5% by 300 mg and 600 mg dosages of ofloxacin, respectively. As adverse reactions, anorexia and nausea occurred in 2 cases. Laboratory anomalies consisted of 1 case of slight and transient elevation of transaminase, and 1 case of elevated serum creatinine.

Administration, Oral↗

Location of signal sequences for membrane insertion of the Na+,K+-ATPase alpha subunit.

To study the membrane insertion of the Na+,K+-ATPase (EC 3.6.1.37) alpha subunit with six to eight transmembrane segments, mRNAs encoding the entire alpha subunit and its four different domains were prepared and translated in rabbit reticulocyte lysate with rough microsomal membranes. On the basis of the resistance of the membrane-inserted products to alkali extraction and the failure to insert the translation products into N-ethylmaleimide-treated membranes, it is suggested that at least two signal sequences are contained within the four transmembrane segments from the amino terminus of the alpha subunit.

Cell Membrane↗

[An experimental study on retentive force of a cone type denture retainer].

This study was made to clarify the retentive force of a denture retainer, i.e., a cone-type stud and sleeve attachment. In order to measure the wearing effect, an engaging and disengaging cycle test of 1,000 times was performed. The effects of taper angle (cone angle), sleeve height and thrusting force at engaging stud and sleeve on retentive force were also analyzed. 1. The cycle test had little effect on the retentive force (P not equal to 0.41). 2. The retentive force became greater with decrease of taper angle (P less than 0.0001). 3. The effect of the sleeve height on retentive force differed with taper angle (P less than 0.0001). 4. The retentive force became greater with increase of thrusting force (P = 0.0009), and this effect was greater as the taper angle decreased (P less than 0.0001). 5. The contributions of the factors were approximately 38% in taper angle, 30% in thrusting force and 2% in sleeve height. 6. It could be interpreted that we had better use the retainer with taper angle of 6 to 8 degrees, although the retainer with taper angle of 5 degrees could be applicable to the tooth on which the less occlusal force transmitted.

Denture Retention↗

[Clinical evaluation for voiding dysfunction in patients with cerebral-palsy].

Urological assessments were done on 132 patients with cerebral palsy, ranging from 5 to 59 years in age (mean 23.2). Concerning urological symptoms, urinary incontinence, decreased urinary stream and urinary tract infection were at 31.8, 14.4 and 16.7%, respectively. Patients with functionally impaired ambulation had a high incidence of urinary incontinence and decreased urinary stream. Decreased urinary stream was more prominent in an elderly patient group, and urinary incontinence was observed almost at the same rate in all age-classified groups. Urodynamic studies were performed in 30 patients with cerebral palsy who were referred to with urological symptoms. The patients were classified into two groups according to the presence or absence of spinal cord lesions. In a group of 15 patients with spinal cord lesions, electromyography of the external sphincter demonstrated detrusor-sphincter dyssynergia (DSD) in 9, of whom 6 complained of decreased urinary stream; while in the group without spinal cord lesions there was no DSD. These findings suggest that the cause of decreased urinary stream in cerebral palsied patients could be explained by DSD secondary to spinal cord lesions.

Adolescent↗

[A case of lupus cystitis].

A case of lupus cystitis in a 23-year-old male is reported. The patient began to complain of diarrhea and vomiting in October, 1985. When the diagnosis of systemic lupus erythematosus (SLE) was established at the Department of Internal Medicine in our hospital, he was referred to our clinic for examination of pollakisuria on November 22. DIP revealed a loss of bladder distensibility, and bilateral hydronephrosis and hydroureter. Transurethral cold cup biopsies revealed subcutaneous edema. A diagnosis of lupus cystitis was made and he was treated with steroids, which resulted in symptomatic and radiographic improvement.

Adult↗

[Acute and chronic effects of a new oral inotropic agent, ibopamine hydrochloride, on hemodynamic and metabolic responses to ergometer exercise in patients with severe congestive heart failure].

The hemodynamic and metabolic effects of ibopamine, an orally active 3,4-diisobutylic ester of N-methyl-dopamine, at rest and during exercise, were evaluated in 8 patients with severe congestive heart failure, initially at 2 hrs after oral 100 mg and after 4 weeks of maintenance therapy (100 mg, 3 times a day). At rest, a single dose of ibopamine increased CI, SVI and SWI, and reduced PCWP, PAm, RA and PVR. These beneficial hemodynamic effects were maintained during supine bicycle exercise: CI and SVI increased markedly (p less than 0.05) and PCWP, PAm, RA and SVR increased at a lower extent (p less than 0.05) after ibopamine than on control conditions. After chronic therapy with the drug, LVDd and CTR decreased (p less than 0.05) and exercise tolerance time increased (p less than 0.01). HR, BPm, double product, norepinephrine, epinephrine, renin activity, aldosterone and lactate/pyruvate did not change significantly after administration of ibopamine. Clinical responses after 4 weeks of maintenance therapy were good in 4 cases and fair in 1 case. No adverse effects were observed. Therefore, ibopamine seems to have not only a positive inotropic action, but also a potent vasodilating action, leading to both afterload and preload reduction and so to be useful for the treatment of severe congestive heart failure at rest and during exercise after acute and chronic therapy with the drug.

Administration, Oral↗