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S Kojima

Publications and source records attributed to S Kojima.

At least 469 records · Page 26Linked to original sources
PubMed1995

Protective effect of N-benzyl-D-glucamine dithiocarbamate against renal toxicity in rats during repeated cis-diamminedichloroplatinum administrations.

The protective effects of N-benzyl-D-glucamine dithiocarbamate (BGD) against the renal toxicity caused by repeated injections of cis-diamminedichloroplatinum (DDP) were studied in rats. The rats were injected i.p. with BGD (2.0 mmol/kg) immediately after i.v. injection of DDP (20 mumol/kg), and after 10 and 20 days they received repeated treatments with the same doses of DDP and BGD. Treatment with BGD prevented nephrotoxicity after repeated DDP administrations. Repeated DDP injections increased lipid peroxidation in the kidney and decreased GSH concentration in the kidney at 5 days after the third injection of DDP. BGD treatment prevented the increase in lipid peroxidation and the decrease in the GSH concentration caused by repeated administration of DDP. The determination of activities of antioxidant enzymes in the kidney showed that catalase activity decreased after repeated DDP administrations and that superoxide dismutase activity tended to decrease. Changes in activities of these enzymes were prevented by BGD treatment. The platinum concentrations in kidney and liver were decreased by BGD treatment. These results indicate that BGD treatment prevents the accumulation of platinum in the kidney after repeated administrations of DDP, resulting in protection against the DDP-induced renal toxicity.

Animals↗
PubMed1995

Expression of MDR-1/P-glycoprotein in childhood acute megakaryoblastic leukemia cells.

Multidrug resistance is a major clinical problem in chemotherapy of malignant disease. Acute megakaryoblastic leukemia (AMKL) is a rare form of childhood leukemia, and is often more resistant to many anticancer chemotherapeutic drugs compared to other types of childhood leukemia. There have been reports of the increased expression in hematologic malignancy of multidrug resistant (mdr-1) gene, which encodes for a transmembrane glycoprotein P-glycoprotein that acts as an efflux pump for structurally unrelated chemotherapeutic drugs. We investigated the malignant cells of 15 newly diagnosed childhood AMKL patients by immunocytochemical analysis and found P-glycoprotein expression in all samples from these patients. RNA prepared from five patients at the time of presentation confirmed the expression of mdr-1 specific message in all cases by Northern blot analysis. These results imply that malignant cells from all childhood AMKL might express the mdr-1/P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Antioxidative activity of 5,6,7,8-tetrahydrobiopterin and its inhibitory effect on paraquat-induced cell toxicity in cultured rat hepatocytes.

The in vitro antioxidative activity of 5,6,7,8-tetrahydrobiopterin (BPH4) was measured and the ability of BPH4 to prevent paraquat-induced cell damage was examined in cultured hepatocytes. The scavenging activity of BPH4 against superoxide anion radicals was assayed in two systems, i.e., xanthine/xanthine oxidase (X/XOD) and rat macrophage/phorbol myristate acetate (M psi/PMA) radical-generating systems. BPH4 showed an extremely strong superoxide anion radical-scavenging activity in both assay systems. Biopterin (BP) itself did not show any activity in the X/XOD system, but was effective in the M psi/PMA system. The antioxidative activities of BPH4 against both superoxide anion and hydroxyl radicals were confirmed by spin trapping-ESR spectrometry. BPH4 also protected rat brain homogenate against auto-oxidation. We further examined the effect of BPH4 on paraquat-induced cell toxicity in cultured rat hepatocytes. The paraquat-induced elevation of the release of lactate dehydrogenase (LDH), a marker enzyme for cytotoxicity from cultured hepatocytes was suppressed by BPH4 in a dose-dependent manner. The elevation of lipid peroxides simultaneously induced by paraquat was also inhibited by BPH4 in the same manner. These results suggest that BPH4 might be useful in the treatment of various diseases whose pathogenesis is active oxygen-related.

Animals↗
PubMed1995

The effects of oligomers content and surface morphology on foreign-body tumorigenesis with polyetherurethanes: two years subcutaneous implantation study in rats.

Three polyurethane materials were prepared by removing and adding the leachable oligomers from and to the same polyetherurethane (PEU). The three PEU materials were dissolved in tetrahydrofuran (THF) and dimethyformamide (DMF) and the solutions were cast on a glass plate to make films of smooth and foamed surfaces, respectively. These six materials and polydimethylsioxane (silicone) were implanted into subcutaneous pocket of rats for 2 years to evaluate the long-term effects around the implant. Among the smooth surface implants, PEU materials induced a higher incidence of tissue responses, including tumor formation than silicone. However, no relationship between the oligomer content and the tissue responses was found. Changing surface morphology from a smooth to a foamed one prolonged the latent period of tumor development and decreased the total tumor incidence.

Analysis of Variance↗
PubMed1995

Acute amiodarone terminates ventricular fibrillation by modifying cellular Ca++ homeostasis in isolated perfused rat hearts.

Intravenous amiodarone has an acute antiarrhythmic action, which may be mediated by effects on intracellular calcium concentration [Ca++]i. We evaluated termination of pacing-induced ventricular fibrillation (VF) and associated changes in [Ca++]i by acute amiodarone in isolated perfused rat hearts loaded with the [Ca++]i indicator 1-(2-amino-5-(6-carboxy-2- indolyl)phenoxy)-2-(2-amino-5-methylphenoxy)ethane-N,N,N',N'-tetraacetic acid pentaacetoxymethyl ester. [Ca++]i was evaluated with surface fluorometry through fiberoptics placed on the interventricular septum. Two minutes after VF induction, hearts were perfused with amiodarone (n = 12, 10 micrograms/ml for 5 min followed by 1 micrograms/ml), low extracellular calcium concentration [Ca++]o (n = 12, 0.2 mM) or a control perfusate (n = 12, no treatment). VF termination during a 30-min observation period was significantly more frequent with amiodarone (92%) and with low [Ca++]o (75%) compared with no treatment (17%, P < .05). In nontreated hearts without recovery, [Ca++]i, expressed as a percentage of the base-line amplitude, increased continuously from 206% +/- 44% to 529% +/- 138% during 30-min VF (P < .05). In hearts that recovered with amiodarone and low [Ca++]o, [Ca++]i decreased significantly from 273% +/- 55% and 273% +/- 99% before treatment to 122% +/- 95% and 50% +/- 80% before defibrillation, respectively (P < .05). VF frequency was also significantly decreased with amiodarone. The nature of [Ca++]i transients in VF has not been fully known. Power spectrum analysis disclosed that [Ca++]i transients responded to every one or two electrocardiographic signals in VF with the highest frequency of 22 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗
PubMed1995

Intracellular calcium transients underlying interval-force relationship in whole rat hearts: effects of calcium antagonists.

OBJECTIVES: Much of the understanding about the cardiac interval-force relationship of the whole heart, including mechanical restitution and postextrasystolic potentiation (PESP), has been inferred from isolated muscle studies. We tested whether results from isolated muscles about intracellular Ca2+([Ca2+]i) transients underlying the interval-force relationship can be substantiated in whole hearts. Additionally, we investigated whether Ca2+ antagonists could alter [Ca2+]i transients underlying mechanical restitution and postextrasystolic potentiation. METHODS: [Ca2+]i transients were studied in isolated perfused rat hearts by surface fluorometry and Indo-1. Using computer-controlled pacing protocols, we performed restitution curves for left ventricular developed pressure and [Ca2+]i (developed pressure and [Ca2+]i plotted as a function of extrasystolic intervals). To quantify restitution curves, we fitted monoexponential functions to plots and analyzed their shift and slope. Then, we used Ca2+ antagonists, low extracellular Ca2+([Ca2+]o) and PESP to modify restitution curves. [Ca2+]i transients in isolated rat hearts were interpreted as Ca2+ released from the sarcoplasmic reticulum. RESULTS: Interval-dependent changes in developed pressure were strongly correlated to interval-dependent changes in the amplitude of [Ca2+]i transients in isolated whole rat hearts. Additionally, nifedipine and low [Ca2+]o led to similar downward shifts but not to a changed slope of restitution curves for [Ca2+]i. On the other hand, PESP increased the slope of restitution curves for [Ca2+]i. Furthermore, the effect of PESP on developed pressure was blunted by high concentrations of Ca2+ antagonists. CONCLUSIONS: The results from isolated muscles about [Ca2+]i transients underlying the interval-force relationship could be substantiated in whole hearts. Additionally, low [Ca2+]i (induced by nifedipine or low [Ca2+]o) decreased the maximal Ca2+ release of the sarcoplasmic reticulum but did not change the release kinetics. On the other hand, PESP presumably accelerated Ca2+ release kinetics of the sarcoplasmic reticulum.

Animals↗
PubMed1995

[An autopsy-verified case of Creutzfeldt-Jakob disease with codon 129 polymorphism and codon 180 point mutation].

An autopsied case of Creutzfeldt-Jakob disease is reported. A 79-year-old Japanese female showed extrapyramidal sign (resting tremor, and rigidity) and dementia. She developed myoclonus and became akinetic within one year from the onset, and then died of pneumonia at age of 81. None of the members of her family had neuromuscular disorders. CT and MRI studies revealed progressive brain atrophy. Consecutive study of EEG did not reveal periodic synchronous discharges (PSD). Codon 129 polymorphism (Met/Val) and codon 180 point mutation (Val/Ile) were detected. The autopsy revealed spongiform change of cerebral cortex and negative Kuru plaques, confirming the diagnosis of Creutzfeldt-Jakob disease. Immunohistochemical study revealed weak synaptic prion staining. Western blot analysis showed positive Proteinase K resistant prion protein. Gene analysis of autopsied brain showed the same prion DNA polymorphism and mutation. The combination of codon 129 polymorphism and 180 point mutation might associate with an atypical clinical form of CJD, which shows the extrapyramidal signs at the onset, and negative PSD in EEG.

Aged↗
PubMed1995

[MRI study of degenerative process in multiple system atrophy].

The characteristic morphological changes of the brainstem and cerebellar regions of multiple system atrophy (MSA) were studied by MRI in varying subtypes, that is olivoponto cerebellar atrophy (OPCA: 23 cases), striatonigral degeneration (SND: 7 cases) and Shy-Drager's syndrome (SDS: 9 cases). OPCA was characterized by atrophy of the entire regions of the brainstem and the cerebellum. SND and SDS tended to show atrophy similar in type but lessin extent to OPCA. The common lesions in MSA were atrophy of the pontine base and cerebellum, and dilation of the fourth ventricle. Atrophy of the pontine base was more dominant in the inferior part than in the superior part, and cerebellar atrophy was more dominant in the superior part than in the inferior part, indicating that degeneration of the pontocerebellar pathway proceeds principally along fibers connecting the inferior part of the pons and the superior part of the cerebellum. Dilation of the fourth ventricle indicated atrophy of the middle cerebellar peduncle. In almost all the cases of OPCA and about a half the cases of SND and SDS, the pontine base and the middle cerebellar peduncle appeared as high signal intensity on T2 weighted image and as low intensity on T1, suggesting degeneration and demylination. In a few cases of OPCA, the dorsolateral part of the putamen were demonstrated as low signal intensity on T2 weighted image.

Adult↗
PubMed1995

Detection of minimal residual disease in patients with childhood common acute lymphoblastic leukemia after autologous bone marrow transplantation with ex vivo purging and systemic IL-2 infusion: unsuccessful prediction of subsequent relapse.

We sequentially analyzed minimal residual disease (MRD) in 7 children with common acute lymphoblastic leukemia (cALL) after autologous bone marrow transplantation (ABMT) with ex vivo purging followed by systemic interleukin-2 infusion. After ABMT, 3 of the 7 patients remained in complete remission (CR) for more than 1 year, and 4 subsequently relapsed. MRD was estimated by polymerase chain reaction amplification to detect the leukemia clone-specific immunoglobulin heavy chain third complementarity determining region (IgH CDR-III). The IgH CDR-III sequences from the relapsed patients were identical with those determined at each respective initial diagnosis. In 2 patients, the levels of MRD were 10(-2) and 10(-5) in the harvested bone marrow (BM) cells, and even after purging the levels were 10(-4) and 10(-5) cells, respectively. One of the 2 patients relapsed 3 months after ABMT, while the other remained in CR for 33 months after ABMT. Among the 4 patients who subsequently relapsed after ABMT, MRD was not detected in the BM samples even 1 month before relapse. Our results suggest that PCR-negativity does not necessarily indicate a lower risk of subsequent relapse. Detection of MRD tends to favor the assessment of the therapeutic effects rather than prediction of relapse.

Base Sequence↗
PubMed1995

[Creatine].

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Adolescent↗
PubMed1995

A new type of advanced third-stage larvae of the genus Gnathostoma in freshwater eels, Fluta alba, from Nakhon Nayok, central Thailand.

Five advanced third-stage larvae of a newly identified type of genus Gnathostoma were collected from freshwater eels, Fluta alba, which were purchased at a market in Nakhon Nayok, central Thailand. The most remarkable characteristic of the newly identified larvae was the larger body size compared with any other larva of Gnathostoma spp. They were also distinguishable from other species by the shape of their hooklets, which branched in a complex manner at the base: this had not been previously observed in any other larval Gnathostoma. The newly described larvae had an average number of 44.5, 45.0, 49.0 and 55.1 hooklets on the head-bulb from the first to the fourth rows, respectively, which were comparable to those of larval G. spinigerum. However, the average number of nuclei in each intestinal cell was 2.21 and fewer than those of the larvae of G. spinigerum. These results suggest that the new type of larvae belong to either G. vietnamicum, G. malaysiae, or constitute a new species of the genus Gnathostoma.

Animals↗
PubMed1994

Effect of an intersubunit disulfide bond on the stability of Streptomyces subtilisin inhibitor.

The effect of an engineered disulfide bond between two identical subunits of a dimeric protein, Streptomyces subtilisin inhibitor, on the stability of the protein was studied by differential scanning calorimetry. The introduction of the linkage caused a large stabilization without changing the cooperativity of unfolding, with the denaturation temperature of a 2 mg/mL solution being increased by 14.3 degrees C to 95.0 degrees C at pH 9.5 and by 16.4 degrees C to 63.0 degrees C at pH 3.0. The stabilization was caused by a loss of denaturational entropy, i.e., -40 and -98 cal K-1 mol-1 at pH 3.0 and 9.5, respectively, which more than compensated for the loss in the denaturational enthalpy.

Bacterial Proteins↗
PubMed1994

Primary structure and inhibitory properties of a subtilisin-chymotrypsin inhibitor from Streptomyces virginiae.

A novel serine protease inhibitor SIL8, which was isolated from the culture medium of Streptomyces virginiae and shown to be a member of the Streptomyces subtilisin-inhibitor-like (SIL) inhibitor family by sequence analysis of its amino-terminal region [Taguchi, S., Kikuchi, H., Kojima, S., Kumagai, I., Nakase, T., Miura, K. & Momose, H. (1993) Biosci. Biotech. Biochem. 57, 522-524], is the first SIL inhibitor demonstrated to show marked inhibitory activity toward alpha-chymotrypsin, in addition to strong inhibitory activity toward subtilisin BPN', a common property of inhibitors of the Streptomyces subtilisin inhibitor (SSI) family. In this study, the complete amino acid sequence of SIL8 was determined from the sequence analysis of peptides obtained by specific cleavage at the reactive site and by enzymic digestion. SIL8 was shown to exist as a dimer protein, each subunit of which was composed of 111 amino acids, and to have less than 50% similarity with other SSI-family inhibitors, indicating its most distant relationship to other members of this family. Insertion of two residues was observed in the flexible loop region of SIL8, and amino acid replacements were found not only on the molecular surface but also in the beta-sheet and hydrophobic core, suggesting that packing rearrangements of the side chains may occur in these regions to maintain the tertiary and quaternary structures. The inhibitor constants Ki obtained using synthetic substrates are 92 pM for subtilisin BPN' and 11 nM for alpha-chymotrypsin. The P1 site was was identified as methionine, which was in good agreement with the substrate specificity of alpha-chymotrypsin. SSI, which also possesses a methionine residue at the P1 site, inhibits alpha-chymotrypsin poorly (inhibitor constant, 4.0 microM). Such a difference in the inhibitory properties of SIL8 and SSI toward alpha-chymotrypsin is discussed on the basis of the structures of the inhibitors.

Amino Acid Sequence↗
PubMed1994

Renaturation of the mature subtilisin BPN' immobilized on agarose beads.

We report here another example of renaturation of subtilisin BPN'(Sbtl) by using an immobilized preparation instead of applying a digestible mutant of Streptomyces subtilisin inhibitor (SSI), a proteinaceous inhibitor of Sbtl [M. Matsubara et al. (1994) FEBS Letters 342, 193-196]. The mature Sbtl was immobilized on agarose beads employing the amino group of the protein. After thorough washing, the immobilized Sbtl was subjected to denaturation in 6 M guanidine hydrochloride (GdnHCl) at pH 2.4 for 4 h, followed by renaturation in 2 M potassium acetate at pH 6.5 for 24 h. This denaturation/renaturation cycle was repeated five times. The recovered activity of the renatured immobilized Sbtl settled at a constant level after the third denaturation/renaturation cycle, demonstrating that almost 100% renaturation was attained by use of the immobilized Sbtl. This immobilized Sbtl preparation could well be utilized for the mechanistic study of protein folding. We then found that 2 M potassium acetate was superior to 2 M potassium chloride as a refolding medium and that the ability of SSI to induce the correct shape of the mature Sbtl was lacking in several refolding media in both thermodynamic and kinetic criteria. Thus the main cause for the increase of refolding yield of Sbtl by coexistence of SSI was prevention of the autolysis of Sbtl.

Amino Acid Sequence↗
PubMed1994

Primary structure and inhibitory properties of a proteinase inhibitor produced by Streptomyces cacaoi.

Protein proteinase inhibitors showing sequence homology with Streptomyces subtilisin inhibitor (SSI) have been found to be distributed widely in Streptomyces species, and accordingly have been named SSI-like (SIL) proteins. SIL1 from S. cacaoi was the first of these proteins to be isolated and to be given a serial number. To study the structure-function relationship of SIL proteins, we determined the primary structure of SIL1 and measured its inhibitory activities. It was found to be composed of 110 amino acids and to exist in dimer form. The amino-acid sequence of SIL1 was unique among other characterized SIL proteins in having a one-residue deletion in two regions and a three-residue insertion in the flexible loop region. Sequence comparison indicated that SIL1 was distantly related to other members of the SSI family, and that amino-acid replacements had occurred not only on the surface of the SIL1 molecule but also in the beta-sheet region. The reactive site of SIL1 was considered to be Arg70-Glu71 from sequence alignment with other SSI-family inhibitors. SIL1 inhibited subtilisin BPN' strongly with an inhibitor constant (Ki) of 2.8 x 10(-11) M, like other members of the SSI family possessing an Arg residue at the P1 site. In contrast, SIL1 exhibited weak inhibition toward trypsin with a Ki value of 5.5 x 10(-8) M, possibly as a consequence of insertion of the three residues in the flexible loop region near the reactive site. This contrast seems to be due to the difference in the subsite structure of the two proteinases.

Amino Acid Sequence↗
PubMed1994

The absence of IgE antibody-mediated augmentation of immune responses in CD23-deficient mice.

The CD23 antigen, a low-affinity receptor for IgE (Fc epsilon RII), is a type II membrane-bound glycoprotein expressed on various cells, particularly mature B cells. A number of functions have been ascribed to CD23, including specific regulation of IgE production, IgE-mediated cytotoxicity and release of mediators, IgE-dependent antigen focusing, promotion of B-cell growth, prevention of germinal center B cells from apoptosis, proliferation of myeloid precursors, and maturation of early thymocytes. It is not clear whether these activities represent in vivo functions. To explore in vivo functions of CD23, we have produced CD23-deficient mice. These mice displayed normal lymphocyte differentiation and could mount normal antibody responses, including IgE responses upon immunization with T-dependent antigens and infection with Nippostrongyrus brasiliensis. Germinal center formation after immunization and in vitro proliferative response of B cells were not affected in mutant mice. However, antigen-specific IgE-mediated enhancement of antibody responses was severely impaired.

Animals↗