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Biomedical subjects

S Kojima

Publications and source records attributed to S Kojima.

At least 415 records · Page 23Linked to original sources

[Combined hormone-chemotherapy for stage D2 prostatic cancer: starting time of chemotherapy in relation to hormone therapy].

We retrospectively analyzed 29 patients with stage D2 prostatic cancer who had been treated with chemotherapy at the urological clinic of Tokyo Medical and Dental University Hospital between 1983 and 1992 to evaluate the efficacy of chemotherapy for advanced prostatic cancer. The patients were divided into three groups according to the starting time of chemotherapy in relation to hormone therapy; 9 patients who received chemotherapy more than four weeks after the initial hormone therapy (group H), 9 patients who received chemotherapy only or in combination with the hormone therapy more than four weeks previously (group C), and 11 patients in whom both therapies were started within four weeks (group HC). Follow-up period ranged from four to 108 months averaging 35. Combination chemotherapy including cisplatin was administered one to 17 times with the median of five. The five-year survival rates estimated by Kaplan-Meier method were 18% in group H, 28% in group C, and 78% in group HC, respectively (HC vs. C: p < 0.05, HC vs. H: p = 0.059). These findings indicate that a combination chemotherapy including cisplatin may improve the prognosis of patients with advanced prostatic cancer when it is started with the initial hormone therapy simultaneously.

Aged↗

Effect of nickel on enzymatic activities in the mouse pancreas.

The effect of nickel (Ni) on the enzymatic activities in the pancreas of mice was studied. Administration of Ni at the dose of 5 mg Ni/kg increased the trypsin activity and decreased carboxypeptidase A activity, but did not affect the activities of chymotrypsin, carboxypeptidase B, amylase, and lipase. Increases in Ca concentrations in the pancreas after Ni administration were observed. In the pancreatic slice experiments, Ni treatment showed a slight decrease in trypsin activity and remarkable decreases in chymotrypsin and carboxypeptidase A activities, and Ca treatment induced increases in the activities of trypsin and carboxypeptidase A. These results suggest that the increase in trypsin activity in the pancreas after Ni administration results from the activation of trypsinogen by the Ca ion and that the decrease in carboxypeptidase A activity is based on the inhibitory effect of Ni on carboxypeptidase A activity.

Animals↗

[The usefulness of percutaneous transhepatic cholecyst puncture (PTCCP) with ultrasoundimage control for acute cholecystitis].

Percutaneous transhepatic cholecyst puncture (PTCCP) is a unique treatment for acute cholecystitis by using of 21 gauge PTC needle with ultrasoundimage control. The procedure is as follows. A percutaneous transhepatic puncture of the gallbladder is made with ultrasonic guidance. After suction removal of the contents of the gallbladder, saline with antibiotics is injected. Finally PTC needle is removed after removal of the injected saline. We carried out PTCCP in 35 patients with acute cholecystitis, and compared its clinical effect with those of PTCCD (46 cases) or conservative treatment of antibiotics administration (38 cases). The treatment of PTCCP removed the clinical symptoms of acute cholecystitis rapidly compared with the conservative treatment and it made the hospitalization shorter compared with the treatment of PTCCD. PTCCP was also performed without any severe complications for patients with underlying diseases. The curative rate of PTCCP was the same as those of other former treatments. It was concluded that PTCCP is a safe, convenient, and useful treatment of acute cholecystitis.

Acute Disease↗

Allogeneic bone marrow and peripheral stem cell transplantation from a haplo-identical mother and CD34 positive selection for CML.

A 6-year-old boy with CML in blastic crisis was transplanted with BM and PBSC from his HLA-mismatched MLC-positive mother following CD34-positive selection. Preconditioning for transplant was with thiotepa, cyclophosphamide, rabbit anti-human thymocyte globulin, and TBI followed by infusion of 2.6 x 10(6)/kg of CD34-positive BM and PBSC. Engraftment was confirmed by FISH analysis, and GVHD was not observed. On day 50, he relapsed and died despite three transfusions of donor lymphocytes without GVHD prophylaxis. CD34-positive cell selection for HLA-mismatched transplantation may prevent severe acute GVHD.

Animals↗

Mechanism of mobilization of cadmium by dithiocarbamates in rat primary hepatocyte cultures.

The mechanism of mobilization of cadmium (Cd) by N-benzyl-D-glucamine dithiocarbamate (BGD) and N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) in rat primary hepatocyte cultures was studied. Probenecid pretreatment increased Cd efflux from the hepatocytes by BGD, but did not affect Cd efflux by HBGD. p-Aminohippurate treatment had no effect on Cd efflux by the chelating agents. These results suggest that an enhancing effect of probenecid on the BGD-induced Cd mobilization is due to its inhibitory effect on the glucuronidation of BGD and not its specific action on BGD transport. Verapamil and nicardipine had no effect on the chelating agent-induced Cd mobilization. Phlorizin did not affect Cd efflux by BGD or HBGD. Phloretin and cytochalasin B inhibited Cd efflux by the chelating agents. These results seem to be evidence that BGD and HBGD may be transported by a facilitated diffusion system in the hepatocytes.

Animals↗

[Characteristic feature in transport of erythrocyte membrane].

This paper gives an overview of recent findings regarding erythrocyte transport. The main transport systems in erythrocyte are Na+, K(+)-ATPase, Ca(2+)-ATPase, anion transport by band 3 protein, water channel and glucose transporter. The kinetics of Na+, K(+)-ATPase had been investigated in detail in several studies and these findings were briefly summarized. The accumulated studies in Ca(2+)-ATPase suggest that the ATPase is also E1/E2 type enzyme. The band 3 protein is most densely distributed protein in the erythrocyte membrane. The anion exchange through band 3 protein is indispensable for CO2 transport from CO2 generating tissues to the lung. The development of molecular biology enabled to discover water channel. The existence of water channel explains the swift movement of water through erythrocyte membrane. The gene for water channel of erythrocyte is designated as AQP1 and is one of gene family, MIP, consisting of 20 genes. The glucose transporter was also identified in the erythrocyte membrane and was named as GLUT1. The transporters involved in Na+, K(+)-cotransport, Na(+)-Li+ countertransport, and Gardos effect remain to be identified.

Biological Transport↗

[Effect of a nitric oxide donor on intraocular pressure].

We examined the effect of nitric oxide (NO) on intraocular pressure (IOP) and aqueous humor dynamics by using a NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP) in rabbits. Intravitreal injection of 20 microliters of SNAP solution (10(-4) to 10(-2)M) reduced IOP from 60 to 120 min after injection. The magnitude of IOP reduction was dose-dependent within 10(-4) and 10(-3)M. The IOP reduction was inhibited by pretreatment with a NO trapping agent, carboxy-PTIO, indicating that IOP reduction was induced by NO released from SNAP. The aqueous flare as assessed with a laser cell flare meter was not accompanied with the IOP reduction indicating that no inflammatory response occurred. Neither tonographic outflow facility nor aqueous flow rate was affected by the treatment with SNAP. We conclude that NO reduces IOP through a mechanism which is not directly involved with the change of conventional outflow or aqueous formation in rabbits.

Animals↗

[Vesico-acetabular fistula occurring 10 years after total hip replacement].

An 85-year-old female, who had had a total hip replacement for osteoarthritis in 1985, presented with gross hematuria in June 1995. Cystoscopy revealed a non-papillary sessile tumor in the right side wall of the urinary bladder with a crateriform opening on the top. Computed tomographic (CT) scan and excretory urography demonstrated a fistulous communication between the bladder and the acetabular bed filled with cement. The biopsy of the mass lesion suggested inflammatory granuloma with powdered cement. Since the lesion was composed of internal fistula, and was not accompanied with infection, the patient was treated conservatively. No external fistula had formed during the 5 months of observation.

Acetabulum↗

Pressor and depressor hormones during alcohol-induced blood pressure reduction in hypertensive patients.

Alcohol acutely causes vasodilation and hypotension in Orientals. To study the mechanisms responsible for the alcohol-induced blood pressure (BP) reduction, we examined levels of various vasoactive hormones after a single intake of alcohol in twelve Japanese men with mild hypertension. On the alcohol intake day, they consumed 1 ml/kg of alcohol with an evening meal, while on the control day they took an isocaloric control drink. BP and vasoactive hormone levels were determined before and 2 h after intake of the alcohol or the control drink. BP after alcohol ingestion was significantly lower than that before drinking or on the control day. This alcohol-induced hypotension was associated with significant increases in heart rate, plasma catecholamines and plasma renin activity (PRA). The changes in heart rate and plasma noradrenaline were inversely related to the changes in BP. Plasma levels of vasopressin and insulin were lower in the alcohol period than in the control period, but these changes were not correlated with the changes in BP. Levels of aldosterone, cortisol, atrial natriuretic peptide, prostaglandin (PG) E2, 6-keto-PGF1 alpha, beta-endorphin, and cyclic GMP were not significantly different between the alcohol and the control periods. These results suggest that changes in pressor hormones may not contribute to the acute hypotensive effect of alcohol, and that the sympathetic nervous system is activated by the BP reduction. The levels of the depressor hormones measured also appear to play no role in alcohol-induced hypotension.

Adult↗

Use of hematopoietic growth factors for treatment of aplastic anemia.

To date, six hematopoietic growth factors, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), interleukin-1 (IL-1), interleukin-6 (IL-6) and erythropoietin (Epo), have been used in the treatment of patients with aplastic anemia (AA). Among them, G-CSF and GM-CSF are effective in correcting neutropenia in some patients with AA, but in general, patients with very severe hypoplasia do not respond to conventional doses of either agent. These factors have been used in the treatment of AA as follows: (1) as adjuvant therapy for severe infections; (2) as adjuvant therapy to immunosuppressive therapy (IS); and (3) as second-line therapy for patients refractory to IS. The results of clinical trials with antilymphocyte globulin, cyclosporine combined with G-CSF have been remarkable both in Europe and in Japan. Ongoing randomized studies with long-term follow-up will reveal the effects of hematopoietic growth factors on both hematopoiesis and the long-term course of the disease, including the later development of clonal disorders.

Adolescent↗

[Shelf-life estimation of pharmaceutical products by matrixing].

The shelf-life estimates of pharmaceutical products obtained by matrixing are compared with those obtained by ordinary analysis, using stability data generated by the Monte Carlo method. The effect of the variation in stability due to different packaging and formulations on the shelf-life estimates is described. Analysis of variance is proposed for the evaluation of shelf-life estimates obtained by matrixing. The relationship between the power of the test and the significance level is discussed as well as the effect of assay error on the power of test.

Analysis of Variance↗

Effects of lanthanide ions on the binding ability of annexin V to phospholipid vesicle.

The effects of lanthanide ions (Ln(3+)), La(3+), Ce(3+), Gd(3+), and Tb(3+), on the binding ability of annexin V to phospholipid vesicle were studied, and compared with that of Ca(2+). The energy transfer following excitation at 278 nm was accompanied by a small decrease (about 3%) in the fluorescence signal (310-315 nm) of the aromatic amino acid residues, followed by strong re-emission of annexin V-bound Tb(3+) at 547 nm. The results of the titration of Tb(3+)-protein interactions using the rate dialysis method suggest that there are two high affinity metal binding sites on annexin V, to which Tb(3+) binds with an average dissociation constant, Kd, of about 2.11 x 10(-7) M. The Ln(3+) seemed to assist the anticoagulant action of annexin V because it binds more strongly to phospholipid than Ca(2+) does. Annexin V had the same ability to bind phospholipids in 10 mu M Ln(3+) as it did in 1 InM Ca(2+), showing that it binds to anionic phospholipids with Ln(3+) more strongly than it does with Ca(2+).

Annexin A5↗

Lysosomal enzyme activities in cultured retinal pigment epithelial and glial cells of RCS rat.

PURPOSE: To compare the activities of acid phosphatase, N-acetyl-beta-glucosaminidase and alpha-mannosidase in cultured retinal pigment epithelium (RPE) and glial cells of Royal College of Surgeons (RCS) rat with those in Long Evans (LE). METHODS: The cultured RPE and glial cells of RCS and LE rat were plated into the same 96 well microtitre, and the biochemical method in microsystem were used for enzyme assays. RESULTS: The activities of acid phosphatase and N-acetyl-beta-glucosaminidase are higher by, respectively, 30% and 46% in cultured RPE of RCS rat than LE rat. The activity of alpha-mannosidase has no significant difference. The activities of 3 enzymes in the retinal glial cells derived from RCS rats are higher than LE rat by 13% to 77%. CONCLUSION: These results suggest that the high activities of lysosomal enzymes in RCS RPE and glial cells may play an important role in the pathogenesis of retinal dystrophy.

Acetylglucosaminidase↗

A case of moderate hypertriglyceridemia with apolipoprotein E phenotype E4/3.

Hyperlipoproteinemic subjects with apo(lipoprotein)E4 are usually hypercholesterolemic and those with apoE2 are hypertriglyceridemic. We report a case of moderate hypertriglyceridemia with apoE phenotype E4/3. Plasma levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL)-C, apoAI, apoB, apoCII, apoCIII, and apoE were 200mg/dL, 451 mg/dL, 31 mg/dL, 115 mg/dL, 99 mg/dL, 10.0 mg/dL, 22.2 mg/dL, and 12.0 mg/dL, respectively. Plasma levels of very low density lipoprotein (VLDL)-C and intermediate density lipoprotein (IDL)-C were high, and those of low density lipoprotein (LDL)-C and HDL2-C were low. All lipoprotein subfractions except VLDL were TG-rich. These findings are common in moderate hypertriglyceridemia. The plasma level of remnant-like particle (RLP, equivalent to chylomicron remnant)-C, was high. The lipoprotein lipase which removes TG from chylomicron and VLDL was normal. The activity of LDL receptor which removes remnants of chylomicron and VLDL as well as LDL was high. ApoE4 actively binds to receptors of remnant and LDL. Thus, the removal of TG-rich lipoproteins should not be impaired in this patient. Plasma levels of insulin during oral glucose tolerance test were high. Hyperinsulinism stimulates VLDL synthesis in the liver. Subjects with apoE4 show active synthesis of chyromicron. Thus, we concluded that the moderate hypertriglyceridemia in this E4/3 patient was due to the overproduction of chylomicron and VLDL.

Adult↗

Effects of chelating agents on testicular toxicity in mice caused by acute exposure to nickel.

N-Benzyl-D-glucaminedithiocarbamate (BGD), diethyldithiocarbamate (DDTC), dihydroxyethyldithiocarbamate (DHED), trans-1,2-cyclohexanediamine N,N,N',N'-tetraacetic acid (CDTA), and meso-2,3-dimercaptosuccinic acid (DMSA) were studied for their protective effects against the testicular toxicity in mice induced by acute exposure to nickel (Ni). Mice were injected intraperitoneally with NiCl2 (5 mgNi/kg) and 30 min or 24 h later, they were injected intraperitoneally with chelating agents (400 mumol/kg). Ni injection increased lipid peroxidation and concentrations of Ca and Fe in the testes, liver, and kidney, and decreased the testicular weight and the fertility rate. At 30 min after Ni treatment, the chelating agents other than CDTA effectively depressed Ni concentration in the testes. At 24 h after Ni treatment, DMSA, BGD, and DDTC were effective in mobilizing Ni from the testes. DMSA, BGD, and CDTA significantly prevented the increase in the lipid peroxidation, the increase in the concentrations of Ca and Fe in the testes, liver, and kidney, and the decrease in the fertility rate caused by Ni injection. Treatment with DMSA or BGD was more effective than that with the others in decreasing the testicular Ni concentration, resulting in effective protection against Ni-induced testicular damage.

Animals↗

Midkine is a heat and acid stable polypeptide capable of enhancing plasminogen activator activity and neurite outgrowth extension.

We studied about the physicochemical stability of a novel heparin-binding growth/differentiation factor, midkine (MK). It was found that synthetic human MK was heat and acid stable. Neither incubation at 80 degrees C for 90 sec nor treatment at low pH affected the elution profile of MK molecule on the high performance liquid chromatography. This physicochemical stability was maintained in the biological activities of MK to enhance plasminogen activator (PA) activity in bovine endothelial cells as well as to promote neurite outgrowth of rat brain cells. A similar stability was observed both with recombinant murine MK and with its homologous protein, recombinant human pleiotrophin. Comparison of physicochemical stability with other several growth factors suggested that MK/pleiotrophin was a unique family of heat and acid stable polypeptides capable of enhancing PA activity and neurite outgrowth.

Animals↗

The amino acid sequence and interaction with the nucleosome core DNA of transition protein 4 from boar late spermatid nuclei.

The primary structure of transition protein 4 (TP4) from boar late spermatid nuclei was determined by automated Edman degradation of S-pyridylethylated protein and of peptides generated by cleavage with Staphylococcus aureus V8 protease, lysyl endopeptidase and CNBr. Boar TP4 is a basic protein consisting of a highly basic amino-terminal half (residues 1-73) and a less basic carboxy-terminal half (residues 74-138). The latter half includes a highly hydrophobic segment, a four-times tandemly repeated sequence, N(G)QNKR(K)X, and a carboxy-terminal segment containing Trp126. Ultraviolet absorption and CD spectra of TP4-rat-liver-nucleosome-core-DNA (double-stranded DNA) complexes suggest a TP4-induced local melting of DNA. Although at 1 mM NaCl TP4 brought about a slight stabilization of the DNA against thermal melting, a destabilization of the DNA was observed at 50 mM NaCl. From the results of quenching of tryptophan (Trp126) fluorescence of TP4 upon its binding to double-stranded and single-stranded boar liver nucleosome-core DNA at 50 mM NaCl, the apparent association constants for the binding of TP4 to double-stranded and single-stranded DNA were calculated to be 7.3 x 10(3) M-1 and 4.1 x 10(3) M-1, respectively. These results suggest that TP4, having different domain structures from TP1-3 and a higher affinity for double-stranded DNA, induces a local destabilization of DNA probably through the stacking of Trp126 with nucleic acid bases.

Amino Acid Sequence↗

Changes in the ratio of branched-chain to aromatic amino acids affect the secretion of albumin in cultured rat hepatocytes.

The effect of branched-chain amino acids (BCAAs) on the synthesis and secretion of albumin was studied in the primary cultures of rat hepatocytes. The changes in the normal BCAAs/aromatic amino acids (AAAs) ratio reduced the secretion of albumin without altering its mRNA levels. Protein-labeling and pulse-chase experiments showed that a low BCAAs/AAAs ratio reduced the biosynthesis, whereas a high ratio accelerated intracellular decay of albumin. These results suggest that normalization of the BCAAs/AAAs ratio improves albumin synthesis while the excess ratio may induce the degradation of albumin in the cells.

Amino Acids, Branched-Chain↗