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M Matsukawa

Publications and source records attributed to M Matsukawa.

At least 73 records · Page 4Linked to original sources

Enzyme-linked immunosorbent assay for TA-2005-glucuronide in human plasma.

A sensitive enzyme-linked immunosorbent assay (ELISA) for TA-2005-glucuronide, a main metabolite of new adrenergic beta-receptor agonist TA-2005, has been investigated without prior deconjugation. Coupling of the hapten with bovine serum albumin (BSA) or beta-D-galactosidase was carried out by the N-hydroxysuccinimide ester method. An anti-TA-2005-glucuronide antiserum was obtained from guinea pig immunized with the hapten-BSA conjugate. The ELISA was based upon a competitive assay in which the separation of bound from free fraction was performed by the double antibody technique using rabbit anti guinea pig immunoglobulin antibody adsorbed to microtiter plates. A satisfactory standard curve for the ELISA of TA-2005-glucuronide was observed in the range of 30 pg-3 ng ml-1 using 25 microliters of human plasma. Inter-day and intra-assay variations were 7.0-17.5% and 1.0-11.7% respectively. The recoveries of TA-2005-glucuronide spiked to plasma samples were 95.5-120% (inter-assay) and 96.0-123.3% (intra-assay). The cross-reactivities of the prepared antiserum with the related compound of TA-2005-glucuronide were quite low though there was a considerable cross-reaction with TA-2005. However, TA-2005-glucuronide could be easily separated from TA-2005 by a simple pretreatment of the plasma sample with a C18 cartridge column. This method was applied to the determination of TA-2005-glucuronide in human plasma samples for the evaluation of the pharmacokinetics of TA-2005. From the results, it was demonstrated that the ELISA developed was useful for the determination of TA-2005-glucuronide in human plasma and that the method was applicable to pharmacokinetic studies in humans.

Administration, Oral↗

Isolation and characterization of novel endogenous digitalis-like factors in the ovary of the giant toad, Bufo marinus.

We have previously described the structures of four novel unconjugated bufadienolides in the ovary of the toad, Bufo marinus. In this study, we report the separation and characterization of three novel bufadienolide conjugates. These compounds were purified by HPLC, and their structures were determined to be 11alpha, 19-dihydroxytelocinobufagin-3-(12-hydroxydodecanoic acid) ester, 11alpha,19-dihydroxytelocinobufagin-3-(14-hydroxy-7-tetra decenoic acid) ester, and 11alpha, 19-dihydroxytelocinobufagin-3-(14-hydroxytetradecanoic acid) ester on the basis of NMR and MS data. Numerous dicarboxylic acid esters of bufadienolides have previously been described, but the three bufadienolide conjugates described in this report differ from previously described esters in that they contain hydroxylated monocarboxylic acids. The function of these three conjugates is not known but they are, like bufotoxins, potent inhibitors of Na+, K+-ATPase and may play a developmental role in the differentiation of toad oocytes.

Animals↗

Expression of intercellular adhesion molecule-1 in mice with Pseudomonas-induced pyelonephritis.

PURPOSE: To investigate the role of intercellular adhesion molecule-1 (ICAM-1) in the renal inflammatory process, we studied the time-course fluctuation of ICAM-1 expression on inflammatory lesions in mice with experimentally induced bacterial pyelonephritis and the effect of in vivo administration of an anti-ICAM-1 monoclonal antibody (mAb) on leukocytic migration. MATERIALS AND METHODS: Ascending pyelonephritis was induced by transurethral instillation of Pseudomonas aeruginosa, and the expression of ICAM-1 in the pyelonephritic lesions was studied by immunohistochemical methods. RESULTS: The expression of ICAM-1 on the pyelonephritic lesions closely paralleled the degree of infiltration of neutrophils and macrophages until 3 days after infection. At 7 days after infection, though the degree of infiltration of these cells was quite high, expression of ICAM-1 was reduced. Treatment with the anti-ICAM-1 mAb in mice with bacterial pyelonephritis resulted in suppression of influx of neutrophils and macrophages in the infected sites until 3 days after infection. However, at 7 days after infection inhibition of the influx of these cells was not seen. CONCLUSIONS: These results suggest that ICAM-1 expression is transient and plays a key role in the influx of neutrophils and macrophages associated with the early-phase response, and that in the late phase ICAM-1 independent adhesion molecules may be more predominant.

Animals↗

Experimental study on the scavenging effects of ginsenosides on oxygen free radicals using model of heterotopic heart transplantation in rats.

Oxygen-derived free radicals play an important role in myocardial injury associated ischemia and reperfusion. To investigate whether ginsenosides, as an additive agent of cardioplegic solution, can decrease toxicity of oxygen free radicals in myocardial injury, a heterotopic heart transplantation model in Wistar rats was employed. St. Thomas II cold cardioplegia containing ginsenosides 80 mg/l was used in the experimental group. St. Thomas II cold cardioplegia alone was used in the control group. After global ischemia for 60 minutes and reperfusion for 30 minutes of a transplanted heart, SOD activity in the myocardium treated with ginsenosides was significantly higher than that in the control group (N=10, p< 0.01), whereas the MDA in the myocardium treated with ginsenosides were markedly lower than that of the control group (p< 0.01). The amounts of oxygen free radicals in the myocardium treated with ginsenosides were significantly lower than that of the control group (p <0.001). This study demonstrates that ginsenosides, as a proper additive agent of cardioplegic solution, can decrease toxicity of oxygen free radicals, suggesting one of the mechanisms for its protective effects against myocardial ischemia and reperfusion injury.

Animals↗

[Long-term results of patients undergone surgical repair for acute type A dissection].

We evaluated the long-term results of 28 operative survivors who underwent surgical repair for acute type A dissection. Residual dissection of the thoracic aorta was found in 21 patients (75.0%) postoperatively, and 6 of them underwent reoperation with no operative death. There were 2 late death; one died in the third operation for thoracoabdominal aorta and the other died of cancer. Two of 4 patients with Marfan's syndrome required total aortic replacement ultimately. Since the elective reoperation can be performed safely, careful follow-up and management is essential for the improved survival of the patients with residual aortic dissection.

Acute Disease↗

[A case of infective thoracic aortic aneurysm ruptured to the lung].

We report a successful surgical treatment of an infective thoracic aortic aneurysm ruptured to the left lung. A 63-year-old man who had been suffering from fever and cough showed twice of hemoptysis. Chest CT revealed a descending thoracic aortic aneurysm ruptured to the left lung. A semiemergent operation was performed. At operation, aneurysm of descending thoracic aorta was found adherent to the left lung. Aneurysmectomy with left pneumonectomy was carried out. The postoperative course of the patient was uneventful. Conceivably, in order to avoid massive intraoperative bleeding during division of dense adhesion and postoperative graft infection, concomitant lung resection is necessary.

Aneurysm, Ruptured↗

Serotonin and acetylcholine are crucial to maintain hippocampal synapses and memory acquisition in rats.

Treatment with serotonin and acetylcholine depletors reduced the number of synapses in the rat hippocampus. Animals that received the drug treatment lost a substantial number of synapses and showed an apparent impairment in memory acquisition. Although the animals were behaviorally impaired following the treatment, spatial memory was nonetheless eventually attained despite the disappearance of long-term potentiation. These data suggest that synapses in the hippocampus that are normally maintained by serotonin and acetylcholine are crucial for normal acquisition of spatial memory. The number of synapses maintained by biogenic amines may be a basic mechanism for neurobehavioral plasticity.

Acetylcholine↗

A new ventriculoperitoneal shunt with a telemetric intracranial pressure sensor: clinical experience in 94 patients with hydrocephalus.

OBJECTIVE: We have developed a telemetric intracranial pressure sensor (OSAKA telesensor; Nagano Keiki Seisakusyo Co. Ltd., Tokyo, Japan) and investigated the clinical usefulness of new ventriculoperitoneal shunting with an OSAKA telesensor, an on-off valve, and a programmable valve. METHODS: The OSAKA telesensor was applied in 94 patients at Osaka Medical College between March 1986 and December 1995. Postoperative management, postoperative course, postural change of intracranial pressure (ICP), and zero drift of the OSAKA telesensor were investigated. RESULTS: ICP was measured easily in all patients with no inconvenience. The setting of the programmable valve was adjusted postoperatively 38 times in 25 patients. Postoperative ICP in the upright position was -14.9 +/- 4.5 mm Hg, and the difference in ICP between the supine and the upright position was about 20 mm Hg. The slope of the decrease in ICP with continuous postural changes from the supine to the upright position was steep until about 30 to 45 degrees but became incrementally less or even rose slightly about this angle. The initial slope was steeper when the shunt was open than when the shunt was closed; it was also steeper postoperatively than preoperatively. This initial slope, therefore, may indicate the intracranial compliance. Seven cases of shunt malfunction were diagnosed correctly by ICP measurements. Zero drift of the OSAKA telesensor was easily corrected by comparing the ICP reading from the telesensor with the puncture pressure in the on-off valve. CONCLUSION: The OSAKA telesensor is very useful in the postoperative care and pathophysiological evaluation of patients with hydrocephalus.

Equipment Design↗

A novel bufadienolide, marinosin, in the skin of the giant toad, Bufo marinus.

We have identified a novel cardiac steroid, 11,19-epoxy-19-methoxytelocinobufagin, named marinosin (1), in the skin of the toad, Bufo marinus (L.) Schneider. The treatment of compound 1 with 50% CH3CN containing 0.1% trifluoroacetic acid yielded a 11 alpha-hydroxyhellebrigenin (2), which has not previously been isolated from animals or plants. The structures of both compounds were established from spectral data obtained by NMR and MS, which were compared with those of a reference bufadienolide, 11 alpha-hydroxytelocinobufagin. Compounds 1 and 2 have A/B cis and C/D cis configuration, which is characteristic of bufadienolides such as bufalin and marinobufagin. However, the stereo-structure of compound 1 was characterized by a boat form of the B ring, which is different from the chair form in typical bufadienolides such as compound 2. Compounds 1 and 2 both exhibited activity, as demonstrated by inhibition of Na+, K(+)-ATPase enzymatic activity and by inhibition of the binding of [3H]ouabain to Na+, K(+)-ATPase; however, marinosin (1) was as less effective inhibitor than 2, 11 alpha-hydroxyhellebrigenin. We have identified compound 2 in toad venom, but not in the skin.

Animals↗

[Permanent pacemaker implantation in patients aged 80 years or older].

Forty-five patients aged 80 years or older at the time of initial permanent pacemaker implantation were followed for 3 to 132 months (mean 40.8). There were 27 males and 18 females. The mean age was 84 years. Acute voltage threshold, lead impedance, R wave amplitude of these patients showed no difference from those of younger patients (< 80 years). Complications occurred in 5 patients as follows: cerebral infarction, 3: perforation, 1; lead displacement, 1. Ten patients died, and main causes of death were decrepitude and cancer. The five-year cumulative survival rate (75.9%) was superior to the expected survival rate (65.8%) by life-table analysis. In conclusion, pacemaker therapy for elderly patients is safe, and seemed to improve their long-term prognosis.

Aged↗

[Quality of life and chemotherapy in terminal stage of gastrointestinal cancers].

A patient in the terminal stage of gastrointestinal cancer is continuously worried by physical and psychological suffering, and asks for treatment to alleviate pain. We have conducted an assessment of the quality of life (QOL) in the terminal stage of cancer, and found a deterioration in active factor and total score of QOL 3 months before death. We have provided active chemotherapy in the terminal stage with the informed consent of the patient. The therapy has aimed at relieving suffering, prolonging survival and maintaining QOL.

Aged↗

Heterogeneity and lability of endogenous digitalis-like substances in the plasma of the toad, Bufo marinus.

Three major groups of endogenous digitalis-like substances (EDLS) have been identified in the plasma of the toad, Bufo marinus. One group of compounds, present in fresh plasma, is composed of chromatographically homogeneous polar conjugates, principally bufadienolide 3-sulfates, which exhibit relatively weak Na(+)-K(+)-adenosinetriphosphatase (ATPase) inhibitory activity. A second and larger group of compounds, also found in fresh plasma, includes chromatographically heterogeneous conjugates, which are effective inhibitors of Na(+)-K(+)-ATPase; these compounds possess properties similar to those of bufotoxins. The third group of EDLS consists of free unconjugated bufadienolides, which are also effective Na(+)-K(+)-ATPase inhibitors. These unconjugated bufadienolides are present in relatively low concentrations in fresh toad plasma, but appreciable quantities are enzymatically generated from conjugates (believed to consist principally of bufotoxins) during the in vitro incubation of plasma. We suggest that the extent to which circulating polar EDLS are enzymatically deconjugated in vivo may be important in the regulation of the digitalis-sensitive Na(+)-K(+)-ATPase of toad brain, the only known digitalis-sensitive Na(+)-K(+)-ATPase in the toad.

Animals↗

Marinoic acid, a novel bufadienolide-related substance in the skin of the giant toad, Bufo marinus.

We found a novel substance, 3 beta-hydroxy-11,12-seco-5 beta, 14 beta-bufa-20,22-dienolide-11,14-olide-12-oic acid (1), which we called marinoic acid, in the skin of the toad, Bufo marinus. The structure was established from NMR and MS data. Like bufadienolides, marinoic acid contained an A/B ring structure in the cis configuration and a D/alpha-pyrone ring structure, but the structure of the C ring differed considerably from that of bufadienolides. Marinoic acid exhibited biological activity, as demonstrated by inhibition of Na+, K(+)-ATPase enzymatic activity, and by inhibition of [3H]ouabain binding to the digitalis receptor site on Na+, K(+)-ATPase, although marinoic acid was a less effective inhibitor than typical bufadienolides. Although marinoic acid cannot be classified as a bufadienolide, its chemical structure and its Na+, K(+)-ATPase inhibitory activity suggest that it is bufadienolide-related.

Animals↗

[Hemobilia].

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Embolization, Therapeutic↗