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Biomedical subjects

M Takasugi

Publications and source records attributed to M Takasugi.

At least 37 records · Page 2Linked to original sources
PubMed1996

Potentiation by ouabain of catecholamine secretion from bovine adrenal chromaffin cells in culture induced by pituitary adenylate cyclase-activating polypeptide: evidence for involvements of Na+ and Ca2+ movements.

The effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on catecholamine secretion with ouabain, an inhibitor of Na(+)-K+ ATPase, in cultured bovine adrenal chromaffin cells was examined, to determine whether movement of Na+, as well as Ca2+, is involved in the secretory process. PACAP (10(-10)-10(-6)M)-induced catecholamine secretion was markedly potentiated by addition of ouabain (10(-5)M). When cultured cells were preincubated with PACAP for 30 min in Ca(2+)-free medium in the presence of ouabain and then stimulated for 15 min with Ca(2+)-containing medium without PACAP or ouabain, their catecholamine secretion was dependent on the external Ca2+ concentration, and 45Ca2+ influx into the cells was increased. When the cells had been preincubated with PACAP and ouabain in Na(+)-free sucrose medium, their Ca(2+)-induced catecholamine secretion was greatly reduced. PACAP increased 22Na+ influx into cells treated with ouabain. These results suggest that stimulation by PACAP and inhibition of the Na(+)-pump both increase the intracellular Na+ level, resulting in increase in Ca2+ influx and catecholamine secretion.

Adenylyl Cyclases↗
PubMed1995

Triple-helix specific ligands stabilize H-DNA conformation.

Under superhelical stress, oligopurine-oligopyrimidine mirror-repeat sequences are able to adopt H-DNA conformations where a triple-helical and a single-stranded structure co-exist. We have previously shown that a benzo[e]pyridoindole derivative (BePI), an antitumor drug interacting more tightly with triplex than with duplex DNA, strongly stabilizes intermolecular triple helices formed upon binding of homopyrimidine oligonucleotides to the major groove of double-stranded DNA at oligopurine-oligopyrimidine sequences. Here we show that an intramolecular triple helix is also strongly stabilized by this ligand. In vitro elongation performed by different DNA polymerases (bacteriophage T7, Escherichia coli or Taq polymerase) could be irreversibly inhibited by the H-DNA structure in the presence of BePI. A mirror-repeat polypurine-polypyrimidine sequence inserted between the E. coli beta-lactamase gene (conferring ampicillin resistance) and its bla promoter strongly inhibited transcription of the beta-lactamase gene in vivo. In the absence of supercoiling, transition to the H-conformation did not occur, but BePI stabilized the H-DNA structure induced by supercoiling as shown by chemical probes (chloroacetaldehyde). The results presented here open a new field of investigation for antitumor agents targeted to a novel class of genetic structures able to regulate gene expression.

Base Sequence↗
PubMed1995

Adrenomedullin increases cyclic AMP more potently than CGRP and amylin in rat renal tubular basolateral membranes.

In rat renal tubular basolateral membranes, the potency to increase cAMP of adrenomedullin (AM), a novel vasorelaxant peptide originally isolated from human pheochromocytoma, was compared with those of calcitonin gene-related peptide (CGRP) and amylin. Although all three peptides raised cAMP in a time- and concentration-dependent manner with a 4-fold increase at 10(-6)-10(-5) M, the EC50 value (10(-9) M) of AM was 100-fold smaller than those of CGRP and amylin. CGRP[8-37], an antagonist for CGRP receptors, attenuated cAMP elevation induced by these peptides with the essentially similar concentration-inhibition curves. These results suggest that the receptors for AM, CGRP and amylin share a common structural homology, and that the receptors sensitive to AM are preferentially expressed in renal tubular basolateral membranes.

Adrenomedullin↗
PubMed1995

Optimal dialysis improves uremic pruritus.

The authors analyzed data on 59 hemodialyzed patients who did not have significant disorders of calcium and phosphate metabolism and found that more than 60% suffered from disabling pruritus possibly related to chronic uremia. Both biochemical correlates of the prevalence of pruritus and dialysis efficacy calculated by urea kinetics were investigated. Significantly higher values of blood urea nitrogen and plasma beta 2-microglobulin just before the dialysis session were observed in pruritic patients with lower dialysis efficacy estimated by Kt/V urea and normalized protein catabolic rate (nPCR). After 3 months without changing the dialysis prescriptions, 16 patients with a mean Kt/V urea and a normalized protein catabolic rate (nPCR) of 1.28 and 1.22 g/kg/d, respectively, experienced significant reductions in the degree of pruritus estimated by the pruritic score, from 12.6 +/- 5.1 to 6.3 +/- 3.2. Twenty-two patients with a mean Kt/V urea and an nPCR of 1.09 and 1.01, respectively, continued to have severe pruritus (score: 12.3 +/- 4.7 to 12.7 +/- 6.4). In 9 of 22 patients with prolonged severe pruritus, dialysis efficacy was heightened with an increase in dialyzer membrane area of more than 0.3 m2. Seven of nine patients with increased dialysis prescriptions had significant reductions of the mean pruritic score, from 12.6 +/- 4.8 to 6.3 +/- 2.4, which inversely related to the significant increase of Kt/V urea from 1.05 +/- 0.25 to 1.24 +/- 0.33; among patients whose dialysis prescriptions were not changed, only one had a significant reduction in score. The authors concluded that higher dialysis efficacy with good nutritional state reduces the prevalence and degree of pruritus in hemodialyzed patients.

Blood Urea Nitrogen↗
PubMed1995

[Studies on attenuation of post-ischemic brain injury by kampo medicines-inhibitory effects of free radical production. II].

It is thought that highly reactive oxygen radicals generated at the ischemia-reperfusion in case of strokes play an important role in damaging the brain. It is well known that lipid peroxidation is propagated by active oxygen radicals, and the the brain is susceptible to the lipid peroxidation. In the previous study, we found that several Chinese herbal medicines and kampo components, which were used for the attenuation of the post-ischemic brain injury, showed a free-radical (OH., O2-. and DPPH) scavenging activity. However, it is not clear whether these Chinese herbal medicines can inhibit the lipid peroxidation reaction or not. In attempting to address this question, we have used three kinds of kampo formulations (Oren-gedoku-to (Huang-Lian-Jie-Du-Tang), Saiko-ka-ryukotsu-borei-to (Chai-Hu-Jia-Long-Gu-Mu-Li-Tang) and Keishi-bukuryo-gan (Gui-Zhi-Fu-Ling-Wan)) to measure the suppressive effect of the lipid peroxidation on the mouse cerebrum using the TBA technique in vitro and in vivo. In vitro experiments, all these Chinese herbal medicines decreased the levels of TBA-reactive substances concentration-dependently. In vivo studies, the levels of the TBA-reactive substance of the cerebrum homogenate of mice treated with these kampo formulations by p.o. for three weeks also decreased. From these results, we suggest that the pharmacological action of Chinese herbal medicines used for the attenuation of the post-ischemic brain damage not only have a free-radical scavenging activity, but also have a suppressive effect on the generation of the lipid peroxidation.

Animals↗
PubMed1995

Primary adrenal ganglioneuroblastoma in an adult.

We present here a case of adrenal incidentaloma in a 35-year-old male. Imaging technology including magnetic resonance imaging (MRI) clarified that the tumor was heterogeneous, and large in size (9x7 cm), and that it originated from the left adrenal gland. MRI scans on T1-weighted sequence showed the tumor with a low signal intensity followed by rapid contrast enhancement, whereas those on T2-weighted sequence showed markedly increased intensity. The tumor was surgically removed, and pathologic diagnosis was well-differentiated ganglioneuroblastoma. Ganglioneuroblastoma in adults is extremely rare, with only about 30 cases documented in people over the age of 20 years.

Adrenal Gland Neoplasms↗
PubMed1995

A dialysis patient with systemic calciphylaxis exhibiting rapidly progressive visceral ischemia and acral gangrene.

Systemic calciphylaxis is a rare, poorly understood syndrome of progressive peripheral ischemic necrosis and medial arterial calcification in patients with end-stage renal disease. We report a patient with this syndrome which developed following corticosteroid administration and who ultimately required amputation of the four extremities. Furthermore, cerebral, myocardial, splenic, and intestinal infarctions also developed in parallel with the increment of visceral arterial calcification. No evidence of noticeable hyperparathyroidism or elevation of serum calcium-phosphate product was observed. We speculated that, in addition to diabetes mellitus and chronic renal failure while undergoing dialysis therapy, the administration of corticosteroids might act synergistically to cause calciphylaxis.

Calciphylaxis↗
PubMed1995

Loop diuretics act directly on adenylate cyclase in rat renal tubular basolateral membranes.

We have reported previously that loop diuretics, especially azosemide and ethacrynic acid, may act not only on the AVP receptor site, but also on the post-AVP receptor site in rat renal tubular basolateral membranes. The purpose of this study was to examine whether loop diuretics (furosemide, azosemide, ethacrynic acid) affect the post-AVP receptor components, using GTP-gamma S, forskolin and cholera toxin as tools acting distal to the receptor. Adenylate cyclase activity stimulated by 10(-9)M AVP was inhibited more potently by azosemide and ethacrynic acid than by furosemide at the concentration of 10(-3) M. Azosemide and ethacrynic acid at concentrations above 10(-4) M also significantly decreased the enzyme activity that was stimulated by 10(-7) M GTP-gamma S and 10(-5)M forskolin, while significant inhibition by furosemide was observed only at 10(-3)M. In addition, the inhibitory effect of these loop diuretics on cholera toxin-stimulated enzyme activity was almost similar to the results observed in AVP-, GTP-gamma S- or forskolin-stimulated the enzyme activity. From these results, we conclude that loop diuretics, especially azosemide and ethacrynic acid, directly affect adenylate cyclase in part as well as the AVP receptor site.

Adenylyl Cyclases↗
PubMed1995

Monitoring changes in cyclosporine dosage by trough level testing.

The concept of a narrow therapeutic window has guided the management of transplant recipients on cyclosporine immunosuppression since its inception more than a decade ago. The need to maintain immunosuppression and avoid toxicity imposed the requirement of monitoring cyclosporine levels within a limited range. The use of circulating trough levels to aid in the adjustment of dosage, however, has also led to controversies. Trough levels did not immediately reflect the dose, and circulating drug levels varied even in the absence of dose changes, indicating the role of factors other than the dose. By introducing a time factor or delay between the dose and trough levels, the sequential delay analysis allows a clearer demonstration of the relationship between doses and trough levels. Using dose adjustments as markers, corresponding changes in the trough levels were observed for most markers after a short delay. The existence of a time factor imposes some restrictions on the scheduling of dose changes and trough level tests. Adjustments in dose need to be separated to avoid interference from each other and the frequency of testing after a change increased to assure its detection. Consideration of the delay should aid in the adjustment of doses and provide an initial step in the understanding of other factors in the relationship between the dose and circulating trough levels.

Chromatography, High Pressure Liquid↗
PubMed1994

Studies on the purine-pyrimidine metabolism (2)--Effects of sample preparation and diet on the concentrations of oxypurines in blood and urine.

The levels of pseudouridine (psi rd), uridine (Urd), hypoxanthine (Hyp), xanthine (Xan) and uric acid (UA) in both blood and urine samples were assayed by a reversed-phase high performance liquid chromatographic (HPLC) method. The evaluation of the sampling procedures showed that the levels of plasma oxypurines were overestimated by more than 15% for Hyp and 35% for Xan when heparinized plasma separation was delayed for 5 minutes after sampling. The fact that oxypurines levels of serum were significantly higher than those of plasma was also documented. Hence, for the accurate measurement of plasma oxypurines, plasma should be immediately separated from the blood with anticoagulants after it is collected. Physiological variation under a suitable sample preparation was also studied in 6 healthy male volunteers after their usual and a low purine diet for 4 days. The mean plasma levels for 6 male volunteers on a usual diet were 2.52 +/- 0.19 mumol/l for psi rd, 290.1 +/- 88.8 for UA, 49.4 +/- 1.24 for Urd, 0.82 +/- 0.30 for Hyp and 0.49 +/- 0.12 for Xan. On a low purine diet, the declines in the plasma oxypurine concentrations and the renal excretions of UA as well as oxypurine were demonstrated. When a dietary purine intake was restricted, the reference range of the Hyp level in plasma wa 0.48 +/- 0.26, and Xan was 0.36 +/- 0.17 mumol/l. Dietary influences on purine-pyrimidine metabolites should also be considered for the accurate measurement of their concentrations in blood and urine.

Chromatography, High Pressure Liquid↗
PubMed1994

[Clinical study on acute bronchitis using inflammatory cytology of sputum].

During fifteen months between January 1989 and March 1990, 137 episodes (136 cases) of acute bronchitis were clinically examined in Iki Public Hospital. From the results of quantitative sputum culture in 99 episodes, 58 episodes (56.8%) had obviously bacterial infections. The three major causative bacteria were H. influenzae (45.7%), S. pneumoniae (27.1%) and B. catarrhalis (17.2%). Inflammatory cytology of the sputum revealed that in the patients with acute bronchitis macrophage, vivid neutrophils and bronchial epithelial cells were clearly observed, while in the patients of chronic respiratory infections those cells were fewer in number. Before and after therapy, respiratory functions and blood gas were evaluated in 45 cases. Significant improvements were observed in PaO2, FEV1.0, etc. During eight years from 1982 to 1989, B. catarrhalis has been gradually increasing, as one of major causative organisms. Each year, the rate of bacterial infection was approximately fifty percent in acute bronchitis.

Acute Disease↗
PubMed1994

Pathogenetic mechanisms involved in mesangial interposition in IgA nephropathy.

To investigate the pathogenetic mechanisms of mesangial interposition (MI) in IgA nephropathy, we examined renal biopsy samples from 20 patients with IgA nephropathy. Electron microscopic morphometric analysis showed that cytoplasmic protrusion of mesangial cells (MCs) into endothelial cells (ECs) or capillary lumina, and widening of the lamina rara interna (LRI) were significantly more prominent in glomeruli with MI than in those without. Immunoelectron microscopy revealed that the ratio of positive endothelial staining with a polyclonal antibody against human platelet-derived growth factor (PDGF) BB was significantly higher in capillary loops with MI than in those without. Enhanced capillary staining of fibronectin related to MI was not recognized. These results suggest that MI in IgA nephropathy is caused by factors such as enhancement of cytoplasmic extensibility of the MCs, widening of the LRI and chemotactic influence of PDGF-BB located in the glomerular ECs.

Adult↗
PubMed1994

[Studies on attenuation of post-ischemic brain injury by kampo medicines-inhibitory effects of free radical production. I].

In view of the recent investigation, highly reactive oxygen-derived free radicals may play a role in cerebral ischemia and brain damage, free radical scavenging activity of kampo formulations (Oren-gedoku-to, Keishi-bukuryogan, Saiko-ka-ryukostu-borei-to and Daio-botampi-to) and Kampo components (Ityou, Shini, Menamomi, Arinosudama and Denshiti), used for the attenuation of brain damage, was investigated in vitro. The used experimental system was a radical scavenging action against 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide anion radical (O2-.) and hydroxyl radical (OH.) by the electron spin resonance technique at room temperature. All kampo formulations and kampo components showed radical scavenging activity in a concentration-dependent manner. This result indicates that kampo formulations, treated for brain damage, were good radical scavenger that could possibly prevent ischemic complications such as formation of brain damage. The intensity of scavening activity of kampo formulations for three types of radicals were as follows; 1. DPPH: Daio-botampi-to > Saiko-ka-ryukotsu-borei-to = Keishi-bukuryo-gan > Oren-gedokuto, 2. O2-.: Daio-botampi-to = Keishi-bukuryo-gan > Saiko-ka-ryukotsu-borei-to > Oren-gedoku-to, 3. OH.: Daio-botampi-to = Saiko-ka-ryukotsu-borei-to > Keishi-bukuryo-gan = Oren-gedoku-to. Daio-botampi-to indicated the strongest scavenging activity against three types of radicals. Ischemic brain damage is thought to be an "oketsu" syndrome, which is correlated with abnormalities of the microcirculation. Therefore, Daio-botampi-to, which has been used for "oketsu" syndrome, showed superior free-radical scavenging activity.

Brain Ischemia↗
PubMed1994

Pharmacologic evaluation of the renal handling of uric acid and oxypurines.

The effect of drugs that alter the renal tubular transport of urate in the renal excretion of the oxypurines, hypoxanthine (Hx) and xanthine (X), was used to analyze the tubular mechanisms involved in oxypurine excretion in normal subjects and in patients with idiopathic renal hypouricemia. In healthy subjects, administration of the drugs, benzbromarone (Bb) and probenecid (Pb), brought a marked uricosuric effect, but did not alter oxypurine excretion. One of 2 hypouricemic patients exhibited no uricosuric effects with Bb and the other showed a slight uricosuric effect with the drug. Bb administration, however, produced no increase in oxypurine excretion in either patient. In healthy subjects, administration of pyrazinamide (PZA) suppressed the excretion of urate and oxypurines to varying degrees: relative to the baseline values, the fraction excretion of urate was reduced by 95% or more, that of Hx by about 24%, and that of X by about 64%. In patients with hypouricemia, the effects of PZA on urate and oxypurine excretion were impaired. According to these findings, we can speculate that the oxypurines have the same renal secretory mechanism as uric acid. However, the reabsorptive mechanisms of oxypurines at the postsecretory site are likely to differ from that of uric acid.

Adult↗
PubMed1993

[A case of Kartagener's syndrome with S. pneumoniae lung abscess].

A 38-year-old male with Kartagener's syndrome (KS) was admitted to our department for evaluation of recurrent pneumonia. Before admission the patient was diagnosed as having pneumonia in another hospital and received ofloxacin (300 mg/day). Fever and production of purulent sputum decreased initially but again increased in the middle of April. On admission the films of both X-ray and CT scan of the chest revealed several air-fluid levels and infiltrative shadows on the left lower lung field. The patient was diagnosed as lung abscess using bronchofiberscopy. Gram staining of the intrabronchial specimens revealed many Gram-positive cocci and neutrophils including phagocytosed bacteria. A new carbapenem (L-627, 600 mg/day), was started intravenously. After the therapy Streptococcus pneumoniae were eradicated soon from the sputum. At the same time the above symptoms including dyspnea on exertion subsided, and the findings of the chest X-ray and CT scan were also improved. Regarding KS the electron micrograph of the cilia showed the absence of the outer-dynein arms. While by both the saccharin test and the sputum cytology impaired mucociliary clearance was found. Lung abscess infrequently accompany KS. There are reports of respiratory infections in KS, but to our knowledge no report of lung abscess was found in KS. We present this case report describing lung abscess in KS.

Adult↗
PubMed1993

[A study on uric acid excretion in patients with hypouricemia].

We studied four patients with hypouricemia and almost normal renal function. Two patients are idiopathic renal and familial. The other two cases are secondary to diabetes mellitus. The study of the uricosuric mechanism with pyrazinamide (PZA) and benzbromarone (Bb) test shows that two patients have a defect of pre-secretory reabsorption of urate, the other one a incomplete combined defect of pre-and post-secretory reabsorption, and the other one a enhanced secretion of urate. The fact that two patients have the history of acute renal failure (ARF) suggested that strenuous exercise or dehydration would be responsible for ARF in patients with renal hypouricemia.

Acute Kidney Injury↗
PubMed1992

Reduction and inactivation of the sarcoplasmic Ca(2+)-ATPase by 2-mercaptoethanol--contrast to the (Na+,K+) ATPase.

The sarcoplasmic Ca(2+)-ATPase was reduced with 300 mM 2-mercaptoethanol at elevated temperatures (40-45 degrees C) with a concomitant loss of ATPase activity. The reduction and inactivation of the Ca(2+)-ATPase proceeded rapidly in the absence of Ca2+. The Ca(2+)-ATPase was also inactivated with 2-mercaptoethanol in the presence of diluted SDS (0.4 mg/ml) even at 20 degrees C. In contrast to the (Na+, K+) ATPase, the inactivated Ca(2+)-ATPase in the presence of diluted SDS was sedimented by the centrifugation at 100,000 x g for 30 min.

Animals↗