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Biomedical subjects

M Kanno

Publications and source records attributed to M Kanno.

At least 145 records · Page 8Linked to original sources

Effects of dofetilide on membrane currents in sinoatrial node cells of rabbit.

The effects of dofetilide (UK 68798) on membrane currents were examined in isolated sinoatrial node cells of rabbits by using patch clamping. At a concentration of 1 microM, dofetilide decreased the delayed rectifier K+ current (IK) (50.2 +/- 10.2%, mean +/- S.E.). The Ca2+ current was slightly decreased during the application of dofetilide. However, the decrease in the current may be attributed to the "run down" phenomenon. The drug did not affect the hyperpolarization-activated inward current. Therefore, dofetilide exhibited class III antiarrhythmic activity in rabbit sinoatrial node cells. Similarly, E-4031 (1-[2- (6-methyl-2-pyridyl)ethyl]-4-(4-methylsulfonylaminobenzoyl)pire ridine) (1 microM), a standard class III agent, also showed specific inhibition of IK. Furthermore, dofetilide depolarized the maximum diastolic potentials, reduced the slope of the pacemaker potential and then abolished spontaneously firing action potentials in the nodal cells. The results demonstrate that dofetilide may produce negative chronotropic effects as a result of its class III activity.

Animals↗

Adult-onset Still's disease with submassive hepatic necrosis.

We present a 74-year old woman who was hospitalized because of typical spiking fever, evanescent rash, polyarthralgia, lymphadenopathy, and marked elevation of serum transaminases and lactate dehydrogenase (LDH) due to adult-onset Still's disease (AOSD) with submassive hepatic necrosis. All of the symptoms and abnormal laboratory findings were dramatically improved after treatment with prednisolone. The clinical course of this patient indicates that AOSD with severe hepatic necrosis can successfully be treated with early administration of corticosteroid, although it remains unknown whether the disease can remain in remission with no or minimal treatment.

Aged↗

[In vitro studies on the combined effects of arbekacin and fosfomycin on methicillin-resistant Staphylococcus aureus].

We investigated the bactericidal activity and post-antibiotic effect (PAE) of arbekacin (ABK) and fosfomycin (FOM) on clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) strain 1936, and the morphological changes of the bacterium. Both antibiotics were used in combination at concentrations lower than their respective MICs. The following results were obtained. 1. When the bacterium was simultaneously exposed to ABK and FOM, growth inhibition and a PAE longer than that effected by ABK alone were observed. 2. When exposed to ABK after treatment with and removal of FOM, bactericidal activity was stronger than that obtained when exposed to ABK alone. However, no increase in bactericidal activity was obtained when exposed to FOM after pretreatment with ABK. 3. Transmission electron microscopy revealed that, when the bacterium was exposed to ABK after treatment with and removal of FOM, large bacterial cells with cross walls at irregular sites and lysed cells showing destruction of the cell wall at the site of bacterial segmentation caused by ABK and FOM. These results demonstrated that ABK in combination with FOM shows stronger bactericidal activity against MRSA in vitro than ABK alone.

Aminoglycosides↗

[Effect of chemotherapy using irinotecan (CPT-11) against recurrent colorectal cancer].

Irinotecan (CPT-11) is a camptothecine derivative with antitumor activity and inhibitor of DNA topoisomerase I. CPT-11 showed a excellent and broad anticancer activity against several malignant tumors. In this study, as in the Japanese phase II study, CPT-11 was administered at 100 mg/m2 weekly by intravenous infusion against 10 patients with recurrent colorectal cancer. Median total dose was 513 mg. Partial responses were obtained in 4/10 patient (40%). Lung metastases showed a 33.3% response and lymphnode metastases showed a 60% response. However, liver metastases showed no response. The median duration to the onset of partial response was 20 days and the median overall response duration was 89 days. Adverse effects were leukopenia (40%), nausea, vomiting and diarrhea (80%), fever (20%), and general malaise (30%). These were generally well tolerated and reversible. From these results, CPT-11 seemed to become an effective drug for recurrent colorectal cancer. Further trials of combination chemotherapy utilizing CPT-11 seem to be warranted.

Adult↗

Attenuated contractile response of diabetic rat aorta to caffeine but not to noradrenaline in Ca(2+)-free medium.

The phasic contractions induced by noradrenaline and caffeine were compared in aortic rings from rats with 8-12 week streptozotocin-induced diabetes and age-matched control rats. In Ca(2+)-free medium, no difference was found in the magnitude of the contractile responses to 10 microM noradrenaline between control and diabetic aortas. The transient contraction induced by 20 mM caffeine was significantly diminished in diabetic aorta compared aorta. The results suggest that the ability of caffeine, but not of inositol 1,4,5-trisphosphate, to mobilize Ca2+ from intracellular stores is impaired in diabetic rat aorta.

Animals↗

Plasma and leukemic cell pharmacokinetics of high-dose N4-behenoyl-1-beta-D-arabinofuranosylcytosine in acute leukemia patients.

The pharmacokinetics of N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BHAC), a lipophilic antitumor analog of 1-beta-D-arabinofuranosylcytosine (ara-C), was investigated, by assay of plasma and leukemic cells of ten acute leukemic patients receiving 60-minute intravenous (IV) infusion of 700 mg/m2 BHAC, for BHAC and 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (ara-CTP) by high-performance liquid chromatography, ara-C by radioimmunoassay, and 1-beta-D-arabinofuranosyluracil (ara-U) by gas chromatography-mass fragmentography. The plasma concentration of BHAC reached a maximum (173.4 +/- 75.3 micrograms/mL) at the end of the infusion and then declined in a biphasic pattern with an initial-phase half-life (t1/2 alpha) of 1.00 +/- .36 hours and a second-phase half-life (t1/2 beta) of 4.28 +/- 2.35 hours. That of ara-C similarly reached a maximum (102.2 +/- 39.9 mg/mL) at the end of the infusion and then declined with t1/2 alpha of 1.37 +/- 1.11 hours and t1/2 beta of 11.2 +/- 4.31 hours. Intracellular ara-CTP concentration increased in a linear-accumulation manner for the first 4 hours after the infusion, reached a maximum of .081 +/- .112 micrograms/10(7) cells at approximately 7 hours, and then declined very slowly in accordance with a one-compartment model with t1/2 of 13.56 +/- 9.62 hours.

Antineoplastic Agents↗

Depressed responsiveness to angiotensin II in ventricular myocytes of hypertrophic cardiomyopathic Syrian hamster.

Electromechanical responsiveness to angiotensin II (Ang II) receptor stimulation in ventricular myocardium and myocytes of hypertrophic cardiomyopathic Syrian hamsters (BIO 14.6) was examined and compared with that in preparations of normal hamsters (F1B) using conventional microelectrode and patch clamp techniques. Action potential duration (APD) and developed tension (DT) corrected for the cross-sectional area of the papillary muscles of 14-20 week-old BIO 14.6 hamsters were significantly smaller than those in preparations of age-matched normal hamsters. An Ang II (1 microM)-induced increase in DT in BIO 14.6 papillary muscles (24.7 +/- 11.0%) was significantly smaller than that in F1B papillary muscles (53.8 +/- 8.5%), which was associated with a smaller increase in APD in BIO 14.6 papillary muscles. In ventricular myocytes of both BIO 14.6 and F1B hamsters. Ang II increased the calcium current (ICa) following a transient decrease in ICa. However, the magnitude of the Ang II-induced increase in ICa in BIO 14.6 myocytes (35.5 +/- 7.5%) was significantly smaller than that in F1B myocytes (86.0 +/- 19.7%), suggesting a causal relationship between ICa and mechanical response to Ang II in these hamsters. The depressed responsiveness to Ang II receptor stimulation in hypertrophic cardiomyopathic hamster is in a marked contrast with the enhanced responsiveness to alpha 1-adrenergic stimulation, which was demonstrated by previous studies, and may be one of adaptational changes to the activated renin-angiotensin system in the cardiomyopathy.

Action Potentials↗

Penetration injury of the pyramis caused by a kick from a racehorse.

A 56-year-old man presented with an unusual cranial penetration injury due to a horse's hoof. The CT number of the hoof was 269, and thus clearly not that of a wooden fragment or bone. An emergency operation was performed to remove the foreign body. The operation went well, and no infection developed. Eight months later he could walk unaided and had only mild disorientation.

Animals↗

Spontaneously perforated pyometra presenting as diffuse peritonitis: report of a case.

We report herein a rare case of spontaneously perforated pyometra found in a 72-year-old woman who was admitted to our hospital with abdominal pain and vomiting. A distended abdomen with muscular rigidity, a positive Blumberg sign, and a WBC count of 11,900/mm3 indicated diffuse peritonitis, although a plain abdominal X-ray film revealed no free air in the peritoneal cavity. An emergency laparotomy was performed, which revealed a lot of pus, and perforation in the fundus of a distended uterus. The patient was therefore diagnosed as having suffered uterine perforation associating with a pyometra, and a total hysterectomy with bilateral salpingo-oophorectomy was carried out. Histological examination revealed a pyometra with inflammation and destruction of the endometrium and myometrium, and cervical occlusion with no evidence of malignancy. Postoperatively, the patient developed a subcutaneous abscess and pneumonia, but recovered and was discharged on the 74th day after her operation. Thus, although rare, spontaneously perforated pyometra should be considered when elderly women present with acute abdominal symptoms.

Aged↗

Enhancement of the positive inotropic effect mediated by alpha 1-adrenoceptors in pertussis toxin-treated rabbit papillary muscles.

1. In rabbit papillary muscles, pretreatment with pertussis toxin (PTX) significantly increased the positive inotropic response to isoprenaline and abolished the inhibitory action of carbachol on the isoprenaline response. 2. Phenylephrine in the presence of propranolol produced a positive inotropic effect and prolonged action potential duration through activation of alpha 1-adrenoceptors. Both of the effects of phenylephrine were significantly enhanced by PTX pretreatment. 3. Accumulation of [3H]inositol monophosphate (IP1) in papillary muscles prelabeled with myo-[3H]inositol was increased by phenylephrine in a concentration-dependent manner, which was antagonized by prazosin. Although PTX pretreatment significantly elevated the basal level of [3H]IP1 formation, the phenylephrine-induced increase in [3H]IP1 formation was unaffected. 4. It is concluded that the cardiac responses to alpha 1-adrenoceptor stimulation studied in these experiments are not transduced by a PTX sensitive G protein (Gi). However, the positive inotropic effect and prolongation of action potential duration mediated by alpha 1-adrenoceptor may be negatively regulated by Gi.

Action Potentials↗

Urine concentrating ability after prolonged sevoflurane anaesthesia.

Few studies have used the vasopressin test to evaluate urine concentrating ability after sevoflurane anaesthesia. We performed a vasopressin test on the first day after operation to compare the effect of prolonged sevoflurane anaesthesia for orthopaedic procedures (n = 11) with that of isoflurane (n = 10). Mean doses of sevoflurane and isoflurane were 10.6 (SE 0.9) and 8.5 (1.5) MAC-h, respectively. Mean peak serum fluoride concentration in patients anaesthetized with sevoflurane was 41.9 (2.5 mumol litre-1 and exceeded 20 mumol litre-1 for approximately 20 h. Each group showed similar responses to vasopressin. There was no evidence of subclinical nephrotoxicity in patients given prolonged sevoflurane anaesthesia.

Adult↗

Beta 1 adrenoceptor mediated decrease in pHi in quiescent ventricular myocardium.

OBJECTIVE: The aims were to examine the effect of beta adrenergic stimulation on the intracellular pH (pHi) and to compare it with that of alpha adrenergic stimulation in ventricular myocardium. METHODS: Using conventional and ion selective electrodes membrane potential and pHi were measured simultaneously in quiescent papillary muscles of guinea pigs in HEPES or bicarbonate buffered solution. Isoprenaline and propranolol (1 microM) plus phenylephrine (30 microM) were used to stimulate beta and alpha adrenoceptors, respectively. In order to evaluate underlying mechanism(s) of beta adrenoceptor mediated pHi change, effects of Na(+)-H+ exchange, Cl(-)-HCO3- exchange, Na(+)-HCO3- symport, and glycolysis blockers on the pHi change were examined. RESULTS: Isoprenaline (1 microM) produced a decrease in pHi of 0.08(SEM 0.01) pH units and a transient depolarisation of the resting membrane. The isoprenaline induced intracellular acidosis was blocked by the beta 1 blocker atenolol (10 microM) but not by the beta 2 blocker ICI 118,551 (0.1 microM). Forskolin also produced a decrease in pHi of 0.06(0.03) pH units. In contrast, alpha adrenergic stimulation produced an increase in pHi, which was abolished by 1 mM amiloride, an Na(+)-H+ exchange blocker. In the presence of amiloride, the isoprenaline induced decrease in pHi was rather enhanced. 4,4'-Diisothiocyanostilbene-2,2'-disulphonic acid (DIDS, 1 mM), a blocker of Cl(-)-HCO3- exchange and the Na(+)-HCO3- symport system, failed to affect the isoprenaline induced pHi decrease in bicarbonate buffered solution. However, pretreatment with 2-deoxyglucose or iodoacetic acid abolished the isoprenaline induced pHi decrease. CONCLUSIONS: beta 1 Adrenoceptor stimulation causes intracellular acidosis via the enhanced glycolysis, and the Na(+)-H+ exchange system appears to play a compensatory role. The beta 1 adrenoceptor mediated intracellular acidosis may modulate inotropic response to adrenergic stimulation in ventricular myocardium.

Adrenergic beta-Antagonists↗

Primary T cell non-Hodgkin's lymphoma of the central nervous system. Case report and review of the literature.

A 42-year-old man developed primary non-Hodgkin's lymphoma of the central nervous system (CNS). Immunohistochemical examination suggested that tumor cells were derived from T cells. Primary T cell non-Hodgkin's lymphoma of the CNS is a rare tumor, with only 12 well-documented cases in the literature. The clinical features of these 12 cases were similar to those of other CNS lymphomas, and the effect of treatment and prognosis were usually worse than those of extranodal lymphoma. Our patient, who was treated with partial tumor resection and whole-brain irradiation with a boost to the primary site and 5 courses of CHOP therapy (cyclophosphamide, doxorubicin, vincristine, prednisolone), is still alive and in remission 38 months after diagnosis.

Adult↗

Histamine receptors mediating a positive inotropic effect in guinea pig and rabbit ventricular myocardium: distribution of the receptors and their possible intracellular coupling processes.

The difference in histamine receptor subtypes that are involved in the positive inotropic effect of histamine in guinea pig and rabbit ventricular myocardium was analytically characterized. In guinea pig papillary muscles, the positive inotropic effect of histamine was antagonized by cimetidine but not by mepyramine. The converse was true in rabbit papillary muscles. However, histamine evoked a positive inotropic effect through H1- and H2-receptors after blockade of H2- and H1-receptors in guinea pig and rabbit papillary muscles, respectively. Adenylate cyclase was significantly activated by histamine via H2-receptors in guinea pig but not in rabbit myocardial ventricular membranes. Accumulation of [3H]inositol monophosphate in ventricular strips prelabeled with myo-[3H]inositol was increased by histamine via H1-receptors to a similar extent in rabbits and guinea pigs. Radioligand binding experiments with [3H]mepyramine and [3H]tiotidine showed an increased number of H1-receptors and a decreased number of H2-receptors in guinea pig compared with rabbit ventricular myocardium. These results suggest that the positive inotropic effects of histamine are dominated by an H1-receptor-mediated effect in rabbits and by an H2-receptor-mediated one in guinea pig ventricular myocardium, and the positive inotropic effect manifested by one subtype apparently restricts the expression of the positive inotropic effect mediated by the other subtype. This species difference is not due to a difference in densities of the receptor subtypes, but may be partly related to a difference in the extents of coupling of H2-receptors to adenylate cyclase.

Adenylyl Cyclases↗

The importance of prevention of sinusoidal endothelial cell injury during cold preservation of liver graft.

We investigated adenosine triphosphate (ATP) synthesis, lipid peroxidation, and activities of radical scavenging enzymes in mitochondria, as well as the ultrastructural morphological changes during cold preservation of swine liver grafts (n = 6) with either Euro Collins (EC) or University of Wisconsin (UW) solutions. The liver, harvested by a standard procedure, was preserved in one of the solutions at 4 degrees C. The values of the total adenine nucleotide and mitochondrial respiratory control ratio (RCR), an index of ATP synthesis, decreased gradually for up to 24 hr during preservation with either of the two solutions and there was no statistical difference between them. Chemiluminescence of mitochondria, an index of lipid peroxidation, in the graft preserved with EC solution or UW solution decreased, and after 24 hr there was no significant difference between the two solutions. Activities of radical scavenging enzymes were well maintained in any of the two solutions. Transmission electron microscopy (TEM) findings showed that the sinusoidal endothelial cells were preserved much better with UW solution than with EC solution even after 12 hr preservation. We concluded that UW solution, more effective for the protection against injuries of the sinusoidal endothelial cells during cold preservation, leads to better results in clinical transplantation, but this solution has no protective effects on energy production, nor radical scavenging enzyme activities of mitochondria. In the maintenance of liver graft viability, protection of the sinusoidal microcirculatory disturbance is more important than that of the mitochondrial function.

Adenosine↗

Six cases of heterochronous gastrointestinal cancer preceded by breast cancer.

Among 432 women with primary breast cancer, six (1.4%) were diagnosed as having gastrointestinal cancer more than six months after operation for the breast cancer. This paper presents these six cases. The patients ranged from 56 to 78 years of age at the time of breast cancer surgery, and the interval after surgery until diagnosis of the second cancer ranged from 7 months to 5 years 1 month. The second cancer was gastric cancer in 3, esophageal cancer in 2, and hepatic cancer in 1. All of the 6 patients had received postoperative adjuvant chemotherapy for breast cancer. The most frequent histological type of breast cancer was solid-tubular carcinoma (3 patients). Three patients died, due to the second cancer, 4 days, 2 months, and 6 months, respectively, after diagnosis of the second cancer, and the other patients are alive 2, 3, and 4 years after diagnosis. The Japanese literature regarding multiple cancer among breast cancer patients is reviewed. It is concluded that care should be taken to examine breast cancer patients with gastrointestinal symptoms, which are likely to be dismissed as a side effect of postoperative chemotherapy.

Aged↗

[Home chemotherapy for peritoneal carcinomatosis].

Nineteen patients diagnosed with peritoneal carcinomatosis were treated by in-home chemotherapy over a period of four years from August, 1990 to July, 1994. Primary diagnoses of the four male and 15 female patients included 12 cases gastric cancer (four males, eight females), five cases of ovarian cancer, one case (female) of appendicular cancer, and one case (female) of breast cancer. In addition to oral administration of UFT-E and 5'-DFUR, chemotherapy included weekly intravenous injection of a massive dose of 5-FU (1,000 mg/m2), subselective intraaortic infusion and intraperitoneal infusion using a reservoir. These methods were used individually and in combination. The drugs used included 5-FU, CBDCA, CPA, THP, and EPIR. Subselective intraaortic infusion was performed by low dose continuous infusion using the Baxter infusor multiday type. Six gastric cancer patients lived normally for over one year, while four died in less than a year. All ovarian and appendicular cancer patients were CR, the breast cancer patient was PR. Ten patients continued working at their jobs while receiving at home chemotherapy treatments. Diuretics were used to alleviats ascites. Although there were no side effects on digestive organs, 5-FU and CBDCA were mixed with 100 mg hydrocortisone in the infusor to improve cachexia, and promote appetite and activity. Bone marrow suppression was very slight at these dosages, and weekly checkups were adequate. The at-home rate (number of days at home/entire period since onset) of all patients was 78%.

Adult↗