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Biomedical subjects

M Kasai

Publications and source records attributed to M Kasai.

At least 343 records · Page 19Linked to original sources

[MR imaging of adenomyosis].

MR imaging characteristics of adenomyosis were studied in nine women (five diffuse type, four focal type) who underwent hysterectomy. In all cases, MR images were correlated with surgical/pathologic findings. On T2-weighted images, diffuse type appeared as a thickening of the junctional zone, because it was often isointense with this zone. Focal type appeared as a low signal intensity, round or oval shaped mass poorly marginated from the adjacent myometrium.

Adult↗

Surgical limitation for biliary atresia: indication for liver transplantation.

Of 245 patients undergoing corrective operations for biliary atresia, jaundice was cleared in 113. In January 1988, 84 of them were living and free of jaundice and the other 19 were alive with jaundice. A vast majority of long-term survivors showed normal growth and development, and were leading normal lives for their respective ages. Portal hypertension, a common late complication, improved spontaneously or after sclerotherapy in jaundice-free patients. Therefore, liver transplantation is not recommended for jaundice-free patients even with esophageal varices. Patients with persistent severe jaundice (serum bilirubin over 10 mg/dL) and those with moderate jaundice (serum bilirubin 5 to 10 mg/dL) and severe esophageal varices require liver transplantation. Patients with moderate jaundice having no or slight varices should be carefully followed. When varices become worse or serum bilirubin rises, liver transplantation is indicated. Patients with mild jaundice (serum bilirubin lower than 5 mg/dL) have a possibility of improvement in their condition before the age of 15 years, and are not recommended for liver transplantation. The high value of the lowest postoperative bilirubin level suggests the necessity of liver transplantation in early childhood. Liver transplantation as the primary treatment for biliary atresia may be indicated only for patients over 120 days of age with an enlarged and hard liver.

Adolescent↗

Disulfonic stilbene derivatives open the Ca2+ release channel of sarcoplasmic reticulum.

Ca2+ channels of isolated sarcoplasmic reticulum were incorporated into a planar lipid bilayer and their pharmacological properties were studied. The results show that the channel is a Ca2+-induced Ca2+ release channel like that observed in skinned muscle fibers and isolated vesicles. (i) The open channel probability was increased by the addition of micromolar amounts of Ca2+ to the cis (myoplasmic) side and further increased by millimolar ATP. (ii) The channel was closed by millimolar Mg2+ and micromolar ruthenium red. We found that two disulfonic stilbene derivatives, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 4-acetoamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), when added to the cis side open the channel and lock it irreversibly at open without changing the single channel conductance. Ca2+ efflux from SR vesicles was also enhanced by SITS and DIDS, as monitored by a tracer assay. Further, Ag+ activated the channel transiently. These results suggest that certain amino and SH residues play important roles in gating the Ca2+ channel.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

A report of a case with pure red cell aplasia induced by sodium valproate.

A 5-year-old girl developed pure red cell aplasia (PRCA) during sodium valproate (VPA) administration. Only four cases of VPA induced PRCA have been reported in the literature. Furthermore no precise report concerning the underlying mechanisms is available. Using a system for the clonal growth of autologous bone marrow committed erythroid stem cells (CFU-E, BFU-E) VPA itself was not inhibitory for colony formation at a physiological concentration. Patient's serum and peripheral mononuclear cells collected at admission showed no inhibitory effects on erythroid progenitor cell growth. Rapid recovery from PRCA was observed after discontinuation of VPA, without immunosuppressive therapy. Our observation suggests that VPA may induce PRCA through the inhibitory effect beyond the differentiation stage of BFU-E and CFU-E in some cases.

Child, Preschool↗

Further characterization of the cation channel of a yeast vacuolar membrane in a planar lipid bilayer.

A voltage-dependent and Ca2(+)-activated cation channel recently found in the vacuolar membrane of the yeast Saccharomyces cerevisiae was incorporated into planar lipid bilayers and further characterized in macroscopic and single channel levels. Single channel conductances for various cations were in the order: NH4+ greater than K+ greater than Rb+ greater than Cs+ greater than Na+ greater than Li+, and were nearly consistent with the order of permeability ratio estimated from reversal potentials determined by macroscopic measurement. Up to 6 mM of Ca2+ added to the cis (cytoplasmic) side opened the channel, but higher concentrations closed the channel without affecting the single channel conductance. Ba2+ closed the channel without affecting the single channel conductance. Ba2+ closed the channel from the cis side. In addition to the above channel, a small cation-selective channel of about 40 pS was found.

Anions↗

Synthesis and antitumor activity of a novel water soluble mitomycin analog; 7-N-[2-[[2-(gamma-L-glutamylamino)ethyl]dithio]ethyl]mitomycin C.

Introducing the mercaptoethyl group at the 7-N position of mitomycin C 1 has led to the isolation of 7-N,7'-N'-dithiodiethylenedimitomycin C 2. The compound 2 showed excellent antitumor activity against sarcoma 180 (sc-ip) and leukemia P388 (ip-ip) in mice. As an extension of this study, we synthesized mitomycin dimers with symmetrical disulfide and mitomycin derivatives with unsymmetrical disulfide at the 7-N side chain. Among these compounds, the water soluble conjugate 3 with ethyl gamma-L-glutamyl-L-cysteinylglycinate was far more effective against sarcoma 180 and leukemia P388 than 1. During the subsequent stage of inquiry for the potent congeners of 3, the compound 4 (water solubility: greater than 500 mg/ml), designated as KW2149, with the gamma-L-glutamylcystamino group at the 7th position was finally selected for further evaluation.

Animals↗

[Clinical study of fluconazole on deep-seated fungal infections].

Fluconazole is a novel antifungal agent, available in oral and intravenous forms, which was developed by Pfizer Central Research. It is characterized by its long serum half-life (approximately 30 hours) to allow once-a-day dosing and favorable safety profile. Fluconazole was administered orally or intravenously to 166 patients with deep-seated mycosis and it was possible to evaluate clinical efficacies in 99 patients. Clinical cures were obtained in 41 (87.2%) out of 47 cases of candidiasis, in 10 (66.7%) out of 15 cases of cryptococcosis, in 17 (48.6%) out of 35 cases of aspergillosis and in 1 case each (100%) of mucormycosis and mycosis due to an unspecified yeast. Side effects were observed in 10 cases (rash 2, fever 2, abdominal discomfort 1, nausea 1, edema 1, edema/pleural effusion/oliguria 1, finger stiffness 1, hiccup 1) with incidence rate of 6.0%. Drug administrations were discontinued in 4 cases. In general, however, fluconazole was well tolerated. Abnormal changes in laboratory test values due to the drug were observed in 32 cases and incidence rate was 19.3%. These were, however, slight and temporary changes and most of them were in parameters of liver function. It is not clear if these changes were related to the fluconazole administration, because other drugs were concomitantly administered to these cases. These results indicate that fluconazole is an agent with very good potential for the treatment of the systemic deep-seated mycoses.

Adolescent↗

[Severe aplastic anemia successfully treated with cyclosporin A and prednisolone].

A 7-year-old boy was admitted to our department complaining pale face and subcutaneous bleeding in August, 1987. Peripheral blood analysis showed pancytopenia of WBC 2,600/microliter, RBC 148 x 10(4)/microliter and platelets 5,000/microliter. Bone marrow biopsy revealed hypocellularity. Granulocytes 104/microliter, reticulocytes 4,290/microliter and platelets 5,000/microliter were compatible with the diagnosis of severe aplastic anemia based on the criteria of the Ministry of Public Welfare in Japan. Prednisolone (PDN) was initially indicated and bolus methylprednisolone, metenolone and ALG therapy followed with no hematological improvement. Fifteen months after admission, in addition to 0.5-1 mg/kg/day of metenolone, Cyclosporin A (CyA) was started at a dose of 12 mg/kg/day for a week and 6 mg/kg/day thereafter. After a week from administration of CyA, 1 mg/kg/day of PDN was given because his bleeding tendency became worse. But this combination was complicated with liver damage and hyperglycemia to discontinue both drugs. These adverse effects were subsided within 7 days by cessation of the drugs. CyA was started again at a dose of 6 mg/kg/day without any response for 4 weeks. Then PDN was added together at a reduced dose of 0.5-1 mg/kg/day. Hematological response was obtained promptly. Granulocytes reached 1,500/microliter, hemoglobin 10.2 g/dl and platelets 26,000/microliter after 3 months of therapy. Afterward the patient became transfusion independent. The most effective method of CyA administration for aplastic anemia is still controversial. Alternative use of CyA, considering combination of steroids or anabolic steroids, in patients who failed to respond to conventional immunosuppressive treatments should be further investigated.

Anemia, Aplastic↗

[A case of essential mesocaval shunt].

Essential mesocaval shunt is very rare entity. A case of chronic cholecystitis with mesocaval shunt from the branch of superior mesenteric vein was reported. This rare hepatofugal pathway was clearly demonstrated by percutaneous transhepatic portography. Selective middle colic venography showed that the branch of this vein was directly connected to the inferior vena cava. After ligation and resection of the shunt, the level of patient's blood ammonia was decreased and the pressure of portal vein was increased. This rare case indicate that the possibility of early diagnosis and interventional radiology for +hepatic encephalopathy.

Aged↗

Separation of peptides by multimode chromatography on a column packed with vinyl alcohol copolymer gel.

Several mechanisms of peptide separation in high-performance liquid chromatography were observed to occur on the Asahipak GS-320 packed with vinyl alcohol copolymer. Neutral rather than acidic mobile phases were employed as they were found to result in higher retention of many peptides on the GS-320. For neutral peptides, the retention volume corresponded to the Rekker's hydrophobic fragmental constant, with a correlation coefficient of 0.71. Peptides with acidic residues eluted early, as an effect of ionic exclusion; those with basic residues were retained longer, owing to an ion-exchange effect. The ionic interactions were shown to involve the carboxylic group present on the gel polymer. The net result was found to be excellent separation of hydrophilic as well as hydrophobic peptides, related to differences in their isoelectric points. The combination of these complex mechanisms, together with the size-exclusion effect of the GS-320 gel for separation of proteins and other large molecules and for analysis with a mobile phase high in acetonitrile content, makes possible high-resolution isocratic analysis of peptides, which cannot be achieved on octadecylsilica or ion-exchange columns.

Amino Acid Sequence↗

The H+/OH- flux localizes around the channel mouth in buffered solution.

The effects of buffering agents present in the solution on the fluxes of H+/OH- through a single channel were theoretically examined under physiological biochemical conditions, i.e. where the concentration of the buffer is in the millimolar range and the pH is around neutral. The solution of the diffusion equation for particles of finite lifetime showed that the convergence permeability can be defined as well as in the case of infinite lifetime, i.e. under non-buffered conditions. The presence of buffers resulted in localization of the H+/OH- fluxes around the channel mouth and enhanced leveling of the ionic concentrations. These results present the basis for arguments on vesicle kinetics and on local chemiosmotic models.

Animals↗

Inhibition by cortisol of neurons in the paraventricular nucleus of the hypothalamus in adrenalectomized rats; an in vitro study.

The effects of cortisol on neurons in the parvocellular division of the paraventricular nucleus (PVN) were investigated in hypothalamic slices prepared from adrenalectomized (ADX) and intact rats. In ADX rats, cortisol inhibited 14 (21%) out of 68 PVN neurons tested at a concentration of 10(-5) M and 11 (16%) of 69 PVN neurons tested at a concentration of 10(-4) M. In intact rats, cortisol at concentrations of 10(-5) M and 10(-4) M did not change the activity of most PVN neurons tested. We conclude that cortisol has an inhibitory effect on neurons in the parvocellular division of the PVN in ADX rats.

Action Potentials↗

Cortisol suppresses noradrenaline-induced excitatory responses of neurons in the paraventricular nucleus; an in vitro study.

The effects of cortisol on noradrenaline (NA)-induced responses of neurons in the parvocellular division of the paraventricular nucleus (PVN) were investigated in hypothalamic slices of rats. Cortisol (10(-5) M)-induced excitation in 7 out of 11 PVN neurons tested and inhibited 3 out of 8 PVN neurons which were not affected by NA. Cortisol alone did not affect the basal firing rate of the PVN neurons. We conclude that cortisol may have an inhibitory effect on neurons in the parvocellular division of the PVN through depression of the noradrenergic system.

Action Potentials↗