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Biomedical subjects

S Yuki

Publications and source records attributed to S Yuki.

At least 19 recordsLinked to original sources
PubMed2005

Treatment of a Gilbert's syndrome patient with irinotecan, leucovorin and 5-fluorouracil.

The patient was an elderly male who had radical surgery for sigmoid cancer in 2001. Owing to metastasis of his cancer to the left supraclavicular lymph nodes in 2002, the patient was admitted to our hospital for systemic chemotherapy. We started treatment with irinotecan, leucovorin, 5-fluorouracil (IFL). After administering 100 mg/m2 of irinotecan, 250 mg/m2 leucovorin and 600 mg/m2 5-fluorouracil to the patient on day 1, grade 3 leukopenia developed rapidly and grade 4 thrombocytopenia was observed on day 5. We excluded irinotecan from the medication and continued the administration of 5-fluorouracil and leucovorin, but his tumors had not been reduced sufficiently. Based on some examination results, we assumed that the patient had Gilbert's syndrome and that the severe side effects that occurred were due to prolongation of SN38 metabolism. We again administered irinotecan but at reduced dose (25 mg/m2). Four courses of this modified IFL were administered safely and the response was favorable.

Aged↗
PubMed1997

Delayed neuronal death prevented by inhibition of increased hydroxyl radical formation in a transient cerebral ischemia.

The salicylate-trapping method was used to detect hydroxyl radicals by measurement of stable adduct dihydroxybenzoic acid (DHBA). Ten minutes of forebrain ischemia followed by reperfusion induced the increase in DHBA in rat hippocampal perfusates. Postischemic treatment with a free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), significantly reduced the increase in DHBA and suppressed delayed neuronal death in the hippocampal CA1 region.

Animals↗
PubMed1997

Effects of a novel free radical scavenger, MCl-186, on ischemic brain damage in the rat distal middle cerebral artery occlusion model.

We investigated the effects of a free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCl-186), on infarct areas, neurological deficits and regional cerebral blood flow (rCBF), with use of a rat thrombotic distal middle cerebral artery (dMCA) occlusion model to elucidate its possible therapeutic effects on focal cerebral ischemia. In addition, we have attempted to measure 2-oxo-3-(phenylhydrazono)-butanoic acid (OPB), which is the major oxidation product of MCl-186, in the penumbral cortex of a thrombotic dMCA occlusion model. Postischemic treatment with MCl-186 (3 mg/kg) significantly (P < .05) decreased the size of the cerebral infarcts 1 day after dMCA occlusion. MCl-186 (3 mg/kg) significantly (P < .05) improved the neurological deficits 1 day after dMCA occlusion. On the contrary, MCl-186 had no effect on rCBF 1 day after dMCA occlusion. MCl-186 mainly reacted into OPB by peroxidation in rat brain homogenates. Furthermore, the increase in OPB content in the ischemic penumbral cortex tissue was confirmed after 90 min of MCl-186 perfusion. These results suggest that MCI-186 has a protective effect on brain ischemia by reacting with oxygen radicals and that oxygen radicals are closely related to postischemic brain injury.

Animals↗
PubMed1996

Effects of a thrombin inhibitor, argatroban, on ischemic brain damage in the rat distal middle cerebral artery occlusion model.

To elucidate the role of thrombin in brain damage during focal cerebral ischemia, we investigated the effects of a selective thrombin inhibitor, argatroban, on microthrombi formation, regional cerebral blood flow (rCBF), infarct areas and neurological deficits using a rat thrombotic distal middle cerebral artery (dMCA) occlusion model. The rat dMCA was occluded by a platelet-rich thrombus formed after photochemical reaction between rose bengal and green light. One day after dMCA occlusion, the number of microthrombi were counted. In the separate animals, rCBF was measured by using the iodoantipyrine method 1 day after dMCA occlusion. Three days after dMCA occlusion, behavioral tests were performed and the size of the cerebral infarction was determined. In the present study, argatroban was administered i.p. by continuous infusion after dMCA occlusion. Argatroban (0.3 mg/h/rat) significantly (P < .05) decreased the number of microthrombi 1 day after dMCA occlusion. Argatroban (0.1 and 0.3 mg/h/rat) significantly (P < .01) reversed a decrease in rCBF 1 day after dMCA occlusion. Argatroban (0.3 mg/h/rat) also significantly (P < .01) reduced the size of the cerebral infarction. Administration of argatroban (0.1 and 0.3 mg/h/rat) resulted in a significant improvement in neurological deficits 3 days after dMCA occlusion (P < .01 and P < .05, respectively). Argatroban decreased the size of the cerebral infarction and improved neurological deficits in the rat thrombotic dMCA occlusion model. These effects were thought to be due to the improvement of rCBF and to the reduction in secondary thrombus formation after dMCA occlusion.

Animals↗
PubMed1995

Synthesis and antipancreatitis activities of novel N-(2-sulfonylamino-5-trifluoromethyl-3-pyridyl)carboxamide derivatives as phospholipase A2 inhibitors.

Novel N-(2-sulfonylamino-5-trifluoromethyl-3-pyridyl)carboxamide derivatives have been prepared and evaluated as phospholipase A2 (PLA2) inhibitors. Among these compounds, IS-741 (sodium salt of 1j), which showed the highest and the most stable therapeutic effect on acute hemorrhagic pancreatitis induced by the closed duodenal loop method in rats, was selected as a candidate for further development.

Acute Disease↗
PubMed1994

Protective effects of MCI-186 on cerebral ischemia: possible involvement of free radical scavenging and antioxidant actions.

The anti-ischemic effects and a possible mechanism of a new antistroke agent, 3-methyl-1-phenyl-pyrazolin-5-one (MCI-186), were studied. Preischemic treatment with MCI-186 (3 mg/kg i.v.) facilitated the recovery of electrocorticographic activity and prolonged survival time in global complete ischemia of rats; MCI-186 (1 and 3 mg/kg i.v.) also mitigated dysfunction of the blood-brain barrier and energy failure in hemispheric embolization of rats. Postischemic treatment with MCI-186 (3 mg/kg i.v.) decreased cortical infarction in focal embolization of rats. MCI-186 (0.6-2.4 mM) inhibited the OH.-induced hydroxylation of salicylate (maximal inhibition, 40.2%), but at 100 microM it did not influence O2- generation. MCI-186 inhibited the formation of linoleic acid-conjugated dienes caused by OH. (IC50 = 32.0 microM). Also, concurrent administration of MCI-186 (3-100 mg/kg i.v.) ameliorated hyperglycemia, hyperlipopeoxidemia and degranulation of beta-cells in alloxan (40 mg/kg i.v.)-treated rats. In addition, MCI-186 inhibited iron-dependent peroxidation in rat brain homogenates and mitochondrial homogenates (IC50 = 15.0 and 2.3 microM, respectively) and prevented iron-dependent peroxidative disintegration of mitochondrial membranes (IC50 = 39.0 microM). These findings suggest that MCI-186 has potent anti-ischemic actions and that its mechanism may be closely associated with beneficial antioxidant activities.

Alloxan↗
PubMed1990

Vinconate prevents ischemic neuronal damage in the rat hippocampus.

The neuroprotective effect of vinconate, a novel vinca alkaloid derivative, was examined in a rat model of forebrain ischemia induced by 4-vessel occlusion. Hippocampal cell loss was quantified histologically 3 days after 10 or 15 min of ischemia. Intraperitoneal application of vinconate (25 and 50 mg/kg) 10 min before and immediately after 10 min of ischemia significantly reduced the neuronal cell loss in the CA1 sector of the hippocampus. Protective effect of vinconate against 15 min of ischemia was reduced, but there was still significant protection at the higher dose. Autoradiography using 14C-vinconate showed that the drug easily penetrates the blood-brain barrier and distributes in the hippocampus. The result suggests that vinconate prevents ischemic neuronal damage by direct action on the hippocampal CA1 neurons.

Animals↗
PubMed1989

Effect of MCI-186 on brain edema in rats.

We induced brain edema in 72 rats by injecting 5 microliters of 3.0% wt:vol polyvinyl acetate into the left internal carotid artery, producing permanent embolization in the left cerebral hemisphere, which developed ipsilateral brain edema reproducibly. Edema was assessed 24 hours after embolization by determining the brain water content and the sodium and potassium concentrations. In this model, the free radical scavenger MCI-186 at 1.0 and 3.0 mg/kg i.v. prevented brain edema in a dose-dependent manner. At 3.0 mg/kg i.v., MCI-186 significantly reduced water content by 1.5% and improved the sodium-potassium balance to within the normal range in the embolized left hemisphere. Dexamethasone at 1.0 mg/kg i.v. did but at 3.0 mg/kg i.v. did not significantly inhibit the development of brain edema. Indomethacin at 4.0 mg/kg i.p. had no effect on brain edema. We suggest that the cyclooxygenase metabolites of arachidonic acid liberated from neuronal cell membrane phospholipids are not likely to be involved in the pathogenesis of permanent brain edema induced by polyvinyl acetate. Our results suggest that MCI-186 attenuates brain edema by suppressing the production of lipoxygenase metabolites, including free radicals or lipid peroxides, and that it may prove valuable for the treatment of brain edema associated with cerebral ischemia.

Animals↗
PubMed1988

Strong attenuation of ischemic and postischemic brain edema in rats by a novel free radical scavenger.

Regional changes in the amount of free fatty acids, polyphosphoinositides, and water content in the cerebral cortex were examined using a middle cerebral artery occlusion model of rats. The amount of various free fatty acids increased as polyphosphoinositides decreased during 3 and 6 hours of ischemia in the occluded middle cerebral artery territory. After 3 hours of reperfusion following 3 hours of ischemia, free fatty acids partially recovered while polyphosphoinositides did not. Water content increased significantly after 3 and 6 hours of ischemia, and a further increase was found after 3 hours of reperfusion following 3 hours of ischemia. The change of polyenoic fatty acids in this occluded middle cerebral artery territory was much smaller than that in the case of decapitation ischemia, although the amounts of polyphosphoinositides and monoenoic and saturated fatty acids showed almost identical changes in both cases, probably because polyenoic fatty acids may be washed out and/or peroxidatively consumed in the middle cerebral artery occlusion model due to its residual blood flow. Changes in the area surrounding the occluded middle cerebral artery territory were similar to the above results, although less dramatic. However, there was no change in free fatty acids, polyphosphoinositides, and water content in the contralateral cortex. A novel free radical scavenger (MCI-186), which prevents both nonenzymatic peroxidation and lipoxygenase activity in vitro, markedly attenuated the ischemic and postischemic brain swelling. These results suggest that free radical mechanisms may be involved in ischemic and postischemic brain edema.

Animals↗
PubMed1987

[Effects of intravenous and intracerebroventricular terazosin, prazosin and clonidine on spontaneous sympathetic outflow in rats].

The hypotensive activity of terazosin has been attributed to inhibition of postsynaptic alpha-1 adrenoceptors. The present study examined the influence of terazosin on spontaneous sympathetic outflow in anesthetize and immobilized rats. The effects on blood pressure and heart rate were also evaluated. Intravenously (i.v.) injected terazosin 0.3 mg/kg and prazosin 0.1 mg/kg increased a sympathetic outflow by 15.4 and 21.6%, respectively. These drugs produced a significant and long-lasting fall in blood pressure with slight heart rate change. On the contrary, clonidine 0.1 mg/kg, i.v. significantly inhibited the sympathetic outflow by 69.2%. The intracerebroventricularly administered 10 micrograms/kg clonidine also showed the sympathoinhibitory effect. However 3 micrograms/kg, i.c.v. of terazosin and prazosin increased the sympathetic tone by 16 and 7.2%. During these periods, in both drugs slightly decreased the blood pressure. These changes in hemodynamic parameters and nerve activities were obtained at 2 approximately 3 min after the i.c.v. administration. The 10 micrograms/kg, i.c.v. of terazosin and prazosin significantly inhibited the pressor response by phenylephrine 1 micrograms/kg, i.v. These results indicate the peripheral effect of terazosin and prazosin through the penetration of the drugs from the brain. The results provide evidence that terazosin, like prazosin, dose not affect cardiovascular regulation by a central action.

Adrenergic alpha-Antagonists↗
PubMed1986

Nucleotide sequence characterization of a Drosophila retrotransposon, 412.

The nucleotide sequence of the internal region of a Drosophila retrotransposon. 412, was determined. The genome of 412 was found to consist of two long open-reading frames (ORFs 1 and 2), an unusually long putative leader region and long terminal repeats (LTRs). As with 17.6, 297 and gypsy, ORFs 1 and 2 slightly overlap each other and are out of phase by +2. ORF2 includes the nucleotide sequences coding for the putative protease, reverse transcriptase and integrase, and is similar in entire organization to the pol gene of Moloney murine leukaemia virus. In spite of the difference in insertion specificity, integrase, an enzyme presumably responsible for insertion, was found to be similar in amino acid sequence to the counterparts of 17.6, 297 and gypsy. There is no ORF in 412 which corresponds to retroviral env or ORF3s of 17.6 and 297. Analysis of 412 transcripts suggested that 412 LTR is composed of U3, R and U5. The gene for a potential primer tRNA for putative reverse transcription of 412 was also surveyed and the 3'-terminal 15 nucleotides of a putative arginine tRNA were found to be exactly complementary to the putative primer-binding site of 412.

Amino Acid Sequence↗
PubMed1986

Structural variations in the Drosophila retrotransposon, 17.6.

More than 21 members of 17.6, a Drosophila retrotransposon, were isolated and their possible structural changes were examined by restriction mapping, blot hybridization, heteroduplex analysis and nucleotide sequence determination of long terminal repeats (LTRs). At least 7 members were found to suffer with terminal or internal long deletions. No pair of LTRs having an identical nucleotide sequence was found either within an element or between elements. Although an initiation site for the presumable genome-sized transcript of 17.6, a potential substrate for reverse transcription on translocation, was identified within the left-hand LTR, our results as a whole support the notion that the majority of 17.6s have continued to reside for a long period of time at their present chromosomal loci and hence the rate of translocation of 17.6 is very low.

Animals↗
PubMed1986

Identification of genes for reverse transcriptase-like enzymes in two Drosophila retrotransposons, 412 and gypsy; a rapid detection method of reverse transcriptase genes using YXDD box probes.

Using synthetic oligonucleotides corresponding to the amino acid sequences best conserved among retroviral reverse transcriptases, we developed a rapid method to detect cloned DNA fragments with the genes for reverse transcriptases. By this technique followed by nucleotide sequence determination, nucleotide sequences coding for reverse transcriptase-like enzymes were identified in two Drosophila retrotransposons, gypsy and 412. Our sequence analysis suggested that there are at least two major groups of retrotransposons in Drosophila with respect to putative reverse transcriptases and both gypsy and 412 belong to a category of retrotransposons which have putative reverse transcriptases very similar in amino acid sequence to the counterpart of Moloney murine leukaemia virus, a typical mammalian retrovirus.

Amino Acid Sequence↗
PubMed1986

Complete nucleotide sequence and genome organization of a Drosophila transposable genetic element, 297.

The complete nucleotide sequence of 297, a Drosophila copia-like transposable element, was determined and compared with those of other similar Drosophila elements and mammalian retrovirus proviruses. It was found that 297 contains three long open reading frames, comparable in sizes and locations with gag, pol, and env genes in the proviruses of replication-competent retroviruses in vertebrates. The first and second open reading frames of 297 exhibit sequence homologies to gag and pol, respectively, of Moloney murine leukaemia virus. In particular, as with 17.6, another Drosophila copia-like element, the second open reading frame of 297 was shown to be very similar in its entire organization to the retroviral pol gene and to consist of three enzymatic domains. By contrast, no appreciable homology was found between the third open reading frame of 297 and the retroviral env gene. It is also suggested that 297 and 17.6 are a peculiar pair of copia-like elements recently diverged from a common progenitor.

Amino Acid Sequence↗
PubMed1985

Close structural resemblance between putative polymerase of a Drosophila transposable genetic element 17.6 and pol gene product of Moloney murine leukaemia virus.

We have made a computer-assisted search for homology among polymerases or putative polymerases of various viruses and a transposable element, the Drosophila copia-like element 17.6. The search revealed that the putative polymerase (second open reading frame) of the copia-like element 17.6 bears close resemblance in overall structural organization to the pol gene product of Moloney murine leukaemia virus (M-MuLV): they show significant homology to each other at both the N- and C-terminal portions, suggesting that the 17.6 putative polymerase carries two enzymatic activities, related to reverse transcriptase and DNA endonuclease. The putative polymerase of cauliflower mosaic virus (CaMV) shows striking homology with the putative polymerase of 17.6 over almost its entire length, but it lacks the DNA endonuclease-related sequence. Furthermore, it was shown that the N-terminal ends of the M-MuLV pol product and the CaMV and 17.6 putative polymerases exhibit strong sequence homology with the gag-specific protease (p15) of Rous sarcoma virus (RSV) as well as the amino acid sequence predicted from the gag/pol spacer sequence of human adult T-cell leukaemia virus (HTLV). These p15-related sequences contain a highly conserved stretch of amino acids which show a close similarity with sequences around the active site amino acids Asp-Thr-Gly of the acid protease family, suggesting that they have an activity similar to acid protease. On the basis of the alignment of reverse transcriptase-related sequences, a dendrogram representing phylogenetic relationships among all the viruses compared together with 17.6 was constructed and its evolutionary implication is discussed.

Amino Acid Sequence↗
PubMed1972

[Amylase].

Explore the source record for details and available documents.

Amylases↗