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Biomedical subjects

T Yoshimura

Publications and source records attributed to T Yoshimura.

At least 127 records · Page 7Linked to original sources
PubMed1999

Involvement of growth-related protein in lipopolysaccharide-induced rabbit arthritis: cooperation between growth-related protein and IL-8, and interrelated regulation among TNFalpha, IL-1, IL-1 receptor antagonist, IL-8, and growth-related protein.

We investigated the functional role of a CXC chemokine, growth-related protein (GRO), in the recruitment of neutrophils in lipopolysaccharide (LPS)-induced rabbit arthritis. The amounts of GRO in the synovial fluids (SF) reached the first peak (major) at 2 hours and the second peak (minor) at 9 hours after injection of LPS into the knee joints. Administration of anti-GRO mouse monoclonal antibody inhibited 54% of the peak leukocyte accumulation at 9 hours (neutrophils greater than 95%), which was similar to the inhibition by anti-IL-8 IgG (48%). Co-administration of these inhibitors increased the inhibition up to 70% at 9 hours and also inhibited 65% of the initial phase of leukocyte infiltration at 2 hours (neutrophils greater than 99%), which was not affected by a single administration of each inhibitor. The amounts of GRO in SF at 2 hours were not altered by either anti-TNFalpha mAb or anti-IL-8 IgG, but reduced by rabbit recombinant IL-1 receptor antagonist (rrlL-1Ra) by 39%. The inhibition by rrlL-1 Ra was augmented further to 59% with coadministered anti-TNFalpha mAb. In contrast, the amounts of GRO at 9 hours were reduced by rrlL-1Ra by 67%. There was no additional reduction in the amounts of GRO at 9 hours by either combination of rrlL-1Ra with anti-TNFalpha mAb or anti-IL-8 IgG. Administration of anti-GRO mAb did not alter TNFalpha or IL-8 contents in SF at their peak (2 hours), but reduced the amounts of IL-1beta at 6 hours and IL-1Ra at 9 hours by 42% and 49%, respectively. These results provide evidence for the following: (a) GRO as well as IL-8 are important mediators involved in the recruitment of neutrophils both in the early and the late phase of LPS-induced arthritis, (b) IL-1 produced in the early phase stimulates GRO production, (c) GRO plays a role in the later induction of IL-1beta and IL-1Ra, and (d) induction of GRO is not regulated by IL-8.

Animals↗
PubMed1999

[Influential factors in elevation of serum creatine phosphokinase for the patients with Kanemi Yusho].

We studied the etiology of the elevation of serum creatin phosphokinase (CK) using the data from routine medical checkup of Kanemi Yusho patients during 1995 and 1997. We also studied the serum CK and blood urea nitrogen (BUN) in rats given the polychlolinated biphenyls as well as controls, and conducted optical microscopic observation of muscle tissue in rats given the polychlolinated biphenyls and control. The patients with elevation of serum creatine phosphokinase also showed the elevation of BUN and polychlolinated biphenyls in their serum. These are thought to be triggers of the elevation of CK in the serum. However, animal experiments failed to yield the same results as human. The rats given polycholorinated biphenyls showed atrophy of muscle fibers. Accordingly, we were unable to clarify the etiology of CK elevation in humans and muscle atrophy in rats.

Animals↗
PubMed1999

[Myasthenia gravis with electrophysiological features of Lambert-Eaton myasthenic syndrome: usefulness of serum autoantibodies assay and neuromuscular junction biopsy].

A 60-year-old man with a 40-year history of seronegative ocular myasthenia gravis (MG) developed generalized weakness cumulating crisis over 2 years. On admission, ophthalmoplegia, severe ptosis and marked generalized weakness were observed without autonomic symptoms and signs. The deep tendon reflexes were decreased, but were normalized after repeated muscle contractions. EMG of the abductor digiti minimi muscle showed low amplitude in compound muscle action potentials (0.6 mV), waxing phenomenon (292%) with 20 Hz repetitive nerve stimulation (RNS), waning phenomenon (34%) in 3 Hz RNS, and posttetanic facilitation (393%). Stimulated single fiber EMG showed reduced jitter with higher stimulation rates. Serum anti-P/Q-type voltage-gated calcium channel antibodies were negative with no evidence of malignancy. Sensitive assay of acetylcholine receptor antibody in serum revealed a positive titer, while conventional assay was negative. A muscle biopsy was performed and immune complex deposition was demonstrated at the endplate. A nearly complete clinical remission and normalization of electrophysiological features followed immunoadsorption and prednisolone therapy. A sensitive immunoassay of acetylcholine receptor antibodies and immunolocalization of complement at the endplate are useful diagnostic tools in cases presenting with features of myasthenia gravis and Lambert-Eaton myasthenic syndrome.

Autoantibodies↗
PubMed1999

Clinical application of adoptive immunotherapy and IL-2 for the treatment of advanced digestive tract cancer.

BACKGROUND/AIMS: We investigated the clinical efficacy of systemic and locoregional adoptive immunotherapy (AIT) with or without interleukin-2 (IL-2) against solid metastatic lesions from digestive tract cancer, which are refractory to conventional chemotherapy or radiotherapy. METHODOLOGY: Seven of 18 patients received hepatic arterial infusion (HAI) of lymphokine-activated killer (LAK) cells with or without IL-2 against metastatic liver tumors (local therapy group). The remaining 11 patients received systemic transfer of LAK cells with IL-2 against metastatic lesions located in organs other than the liver (systemic therapy group). RESULTS: Three of the 7 local therapy group patients showed clinically significant tumor regressions and this was evaluated as being equivalent to partial response (PR) (response rate: 43%). Two of the 11 systemic therapy group patients showed tumor regression which was evaluated as being equivalent to either complete response (CR) or PR (response rate: 18%). These 2 effective cases in the systemic therapy group were esophageal cancer patients. CONCLUSIONS: Locoregional AIT with or without IL-2 against liver metastases of digestive tract cancer could be an effective therapeutic modality in some patients who are refractory to conventional therapies. However, clinical efficacy of systemic AIT with IL-2 against metastases of digestive tract cancer would not be an effective modality except for the metastases of esophageal cancer.

Adult↗
PubMed1999

[A case of spinal myoclonus associated with epidural block for lumbago].

We herein report a case of spinal myoclonus following the administration of epidural anesthesia. A 25-year-old woman underwent lumbar epidural anesthesia because of lumbago and cramps in her left lower limb. She immediately felt a lancinating pain in her left limb during anesthesia at the level of L 4/5 and soon developed myoclonus in her left thigh. The neurological examination revealed rhythmic myoclonus in the left quadriceps and adductor thigh muscles. The myoclonus disappeared after performing a blockade of the left L 4 spinal root by using 1.5 ml of 1% lidocaine. An injury to the left L 4 nerve root during the epidural anesthesia possibly caused an abnormal transmission of the impulses or ectopic hyperexcitability in the nerve root, which might lead to the disturbance of the spinal inhibitory interneurons and hyperexcitability of the anterior horn cells causing myoclonus. Since she did not demonstrate any muscular weakness, nor sensory loss during the lidocaine block, the 1% lidocaine appeared to block the sympathetic nerves or to suppress the ectopic hyperexcitability. The sympathetic nerves may be involved in the development of her spinal myoclonus.

Adult↗
PubMed1999

Absorption, distribution, metabolism, and excretion of donepezil (Aricept) after a single oral administration to Rat.

Donepezil hydrochloride (Aricept) is a drug for the treatment of Alzheimer's disease. The absorption, distribution, metabolism, and excretion of donepezil were investigated in male Sprague-Dawley rats after a single oral administration. Orally administered (14)C-labeled donepezil was absorbed rapidly. The plasma level of unchanged donepezil declined more rapidly than that of radioactivity, and the brain level of radioactivity declined almost in parallel with the plasma level of unchanged donepezil. The ratio of donepezil to total radioactivity in brain was 86.9 to 93.0%, indicating low permeability of the metabolites through the blood-brain barrier. No heterogeneous localization of radioactivity was recognized in the brain and the concentration in each part of the brain was 1.74 to 2.24 times the plasma concentration. Cumulative biliary, urinary, and fecal excretion of radioactivity in bile duct-cannulated rats was 72.9, 24.4, and 8.84%, respectively, of the administered radioactivity at 48 h after administration. These results indicate that the absorption of donepezil is almost complete, and that its metabolites are mainly excreted into feces through the bile and some of them are subject to enterohepatic circulation. The metabolism of donepezil was extensive in rats and involved O-demethylation, aromatic hydroxylation, N-dealkylation, N-oxidation, and glucuronide conjugation of O-demethylate. The structures of the metabolites were determined by mass spectrometry and (1)H-NMR analysis. In plasma, urine, and bile, O-glucuronides accounted for the majority of the radioactivity, and in brain, unchanged donepezil was mostly detected. No metabolites were found in brain. There was no notable accumulation of radioactivity in whole blood and tissues.

Administration, Oral↗
PubMed1999

[A case of Behçet's disease presenting cerebral infarction due to occlusions of the bilateral internal carotid arteries].

This is a case report of a 41-year-old man with Behçet's disease who suffered from cerebral infarction due to complete occlusions of the bilateral internal carotid arteries. His illness began at age 23 with blurred vision of the right eye. The last few years he complained of recurrent painful ulcers on the mucosa or skin of the mouth and the external genitalia. In August 1998, he was admitted to our hospital in an acute confusional state with right hemiplegia. Head CT scans and MRIs revealed acute and subacute ischemic lesions in the left frontal lobe and some other regions of the bilateral hemispheres. Carotid angiography showed complete occlusions of the bilateral internal carotid arteries just rostral to the bifurcations. He did not have any histories of hypertension nor other risks for cerebrovascular diseases. Although direct evidence for the cause of carotid occlusions was not obtained, we speculated that his cervical lesions came from the arterial changes attributable to vasculo-Behçet's disease. Vascular involvements are not infrequent in Behçet's disease, but we believe such occlusive lesions in the bilateral internal carotid arteries as seen in our case are extremely rare. As a construction worker he had undergone a lot of mechanical stress on his neck, which might be a trigger for the carotid lesions.

Adult↗
PubMed1999

[A case of Sweet's syndrome (acute febrile neutrophilic dermatosis) showing transient jargon aphasia].

A 54-year-old woman visited our emergency service complaining of a severe language disturbance. She was fluently speaking something but most of the words were merely meaningless syllables. This jargon state lasted only four hours, then her abnormal speech rapidly and completely recovered within 24 hours. She had also suffered from painful oral ulcers, fever and erythema-like eruptions on her face for about three weeks. Skin biopsy of a facial lesion revealed a dense infiltrate of neutrophils in the dermis and minimal features of vasculitis, which, with other typical clinical findings, led us to the diagnosis of Sweet's syndrome. Although head CT scans, MRIs, MRA or SPECT could not detect any brain lesions, a cerebrospinal fluid examination showed a mild pleocytosis of 38/mm3 with 47% polymorphonuclear cells. There have been a few case reports on Sweet's syndrome accompanying neurologic symptoms, most of which are mild meningitis. We speculate that the transient aphasia was due to a focal lesion in the central nervous system attributable to Sweet's syndrome. Sweet's syndrome might bring inflammatory or ischemic lesions to the cerebrum as Behçet's disease.

Acute Disease↗
PubMed1998

Transamination as a side-reaction catalyzed by alanine racemase of Bacillus stearothermophilus.

The pyridoxal form of alanine racemase of Bacillus stearothermophilus was converted to the pyridoxamine form by incubation with its natural substrate, D- or L-alanine, under acidic conditions: the enzyme loses its racemase activity concomitantly. The pyridoxamine form of the enzyme returned to the pyridoxal form by incubation with pyruvate at alkaline pH. Thus, alanine racemase catalyzes transamination as a side function. In fact, the apo-form of the enzyme abstracted tritium from [4'-3H]pyridoxamine in the presence of pyruvate. A mutant enzyme containing alanine substituted for Lys39, whose epsilon-amino group forms a Schiff base with the C4' aldehyde of pyridoxal 5'-phosphate in the wild-type enzyme, was inactive as a catalyst for racemization as well as transamination. However, when methylamine was added to the mutant enzyme, it became active in both reactions. These results suggest that the epsilon-amino group of Lys39 participates in both racemization and transamination when catalyzed by the wild-type enzyme.

Alanine Racemase↗
PubMed1998

Hsc62, a new DnaK homologue of Escherichia coli.

We have cloned and expressed the ORF o170#1 of Escherichia coli, which encodes a 62-kDa protein sharing 33% homology in primary structure with DnaK and Hsc66, Hsp70 homologues of E. coli. The purified gene product, which we named Hsc62, clearly showed ATPase activity and was bound to a gelatin-agarose gel, from which it was specifically eluted with ATP magnesium salt. Thus, Hsc62 is similar to DnaK in this respect and probably functions as a molecular chaperon in E. coli. However, Hsc62 differs markedly from DnaK and also from Hsc66 in response to temperature: the optimum temperature for ATPase activity was increased stepwise in the order of Hsc62, Hsc66, and DnaK. Hsc66 is activated by DnaJ of E. coli in the same manner as DnaK, the natural partner protein of DnaJ. However, Hsc62 is distinct from the others: the ATPase activity of Hsc62 was not elevated by DnaJ.

Adenosine Triphosphatases↗
PubMed1998

Diastereoselective two-directional synthesis and cation transport ability of the central tristetrahydrofuranyl unit of meso polyether glabrescol as naturally occurring podand.

The diastereoselective synthesis of the central 2,5-linked tristetrahydrofuran (trisTHF) 6 of naturally occurring meso polyether, glabrescol (5), has been achieved in a two-directional manner by the vanadium(V)-catalyzed anti oxidative cyclizations of diol 14. The trisTHF podand 6 and its stereoisomeric analogs 7 and 8 exhibited outstanding cation transport abilities for physiologically important Na+ and K+.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Positive regulation of the human macrophage stimulating protein gene transcription. Identification of a new hepatocyte nuclear factor-4 (HNF-4) binding element and evidence that indicates direct association between NF-Y and HNF-4.

We previously reported that the transcription of the human macrophage stimulating protein (MSP) gene was positively regulated by the binding of NF-Y to the CAATT sequence in the promoter region of this gene. Here we confirmed our previous results and further characterized the MSP promoter. Luciferase assay with deletion constructs showed the importance of the region, +32 to +39, for the promoter activity in Hep3B cells. Two nuclear protein-DNA probe (+15 to +40) complexes, C1 and C2, were detected by electrophoretic mobility shift assay. C2 was specific to hepatoma cells and contained hepatocyte nuclear factor-4 (HNF-4). DNase I footprinting with recombinant HNF-4 located another HNF-4-binding site in the distal region, -89 to -54. Mutations in the CAATT or the proximal HNF-4-binding site significantly reduced the promoter activity in Hep3B cells and HNF-4-transfected HeLa cells, whereas mutations in the distal HNF-4-binding site had no effect. The close proximity between the CAATT and the proximal HNF-4-binding site suggested that a direct contact between NF-Y and HNF-4 might be important. Protein-protein interaction between the A-subunit of NF-Y and HNF-4 was detected by a yeast two-hybrid system. The binding of in vitro translated HNF-4 to immobilized NF-YA and in vitro translated NF-YA to immobilized HNF-4 was also detected. These results suggest the binding of HNF-4 to the proximal HNF-4-binding site directs the basal transcription of the MSP gene, and the maximal promoter activity may depend on the direct association between HNF-4 and NF-Y.

Base Sequence↗
PubMed1998

Nucleotide sequence of Bombyx mori cytoplasmic polyhedrosis virus segment 8.

The segments 8 (S8) of the 10 double-stranded RNA genomes from Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) strains I and H were converted into cDNAs, amplified by PCR, and cloned. The nucleotide sequence analysis of the two full-length S8 cDNAs showed that the segments consist of 1328 nucleotides encoding putative proteins (p44) of 390 amino acids with molecular masses of about 44 kDa, which have glutamic acid-rich and proline-rich domains in their central regions. They had quite high identity with each other: about 98% in nucleotide and amino acid sequences. The recombinant p44 expressed in BmN4 cells using the baculovirus vector was detected by immunoblot analysis. p44 was also confirmed with the same antiserum to be present in BmCPV-infected midgut cells, but not in polyhedra, virus virions and uninfected midgut cells, indicating that p44 is expressed as a nonstructural protein of BmCPV.

Amino Acid Sequence↗
PubMed1998

Plasmin can reduce the function of human beta2 glycoprotein I by cleaving domain V into a nicked form.

beta2-Glycoprotein I (beta2GPI) is a highly glycosylated plasma protein with the ability to bind negatively charged substances such as DNA, heparin, dextran sulfate, and negatively charged phospholipids. The most relevant physiological role of beta2GPI is supposed to be the regulation of the function of anionic phospholipids like cardiolipin (CL). beta2GPI consists of a single polypeptide chain (326 amino acid residues) with a molecular mass of about 50 kD and with five tandem repeated domains (I, II, III, IV, and V). In the previous study, we found that factor Xa can produce the nicked form by cleaving Lys 317-Thr 318, using recombinant human domain V (r-Domain V). However, the reaction was extremely slow. In the present paper, we found that plasmin can produce the nicked form of domain V, using recombinant domain V (r-Domain V) and beta2GPI from human plasma. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, r-Domain V was rapidly cleaved into a nicked form by plasmin, very slowly by factor Xa, but not by thrombin, tissue-type plasminogen activator, urokinase, and tissue factor/factor VIIa. The cleavage site of r-Domain V and beta2GPI by plasmin was proved to be Lys 317-Thr 318 by amino acid sequence analysis of the digest and of the C-terminal peptide isolated by high-performance liquid chromatography. The cleavage was completely inhibited by plasmin inhibitor (alpha2PI). The nicked form was demonstrated to show reduced affinity for CL with a dissociation constant of one order of magnitude larger than that of the intact beta2GPI. To determine whether the specific cleavage of beta2GPI by plasmin can occur also in plasma, human plasma was first acid-treated to inactivate alpha2PI and then incubated with urokinase. About 12% of beta2GPI in plasma was nicked when alpha2PI activity decreased to 80%. The nicked form was not generated in plasminogen-depleted plasma. These results suggest that plasmin can produce the nicked form of beta2GPI with the reduced ability to bind phospholipids in vivo.

Amino Acid Sequence↗
PubMed1998

Occurrence of pyridoxal 5'-phosphate-dependent serine racemase in silkworm, Bombyx mori.

D-Serine is known to occur in the silkworm Bombyx mori as well as in the mammalian central nervous systems. We found that serine racemase occurs in the insect, catalyzing the conversion of L-serine to its antipode. The enzyme was partially purified from pupae of the insect, and was inactivated by treatment with hydroxylamine and reactivated with pyridoxal 5'-phosphate (PLP). L-Alanine was racemized slowly by the enzyme at a rate of only about 6% of that of L-serine, and L-arginine and L-glutamine were inert as substrates. Therefore, the enzyme is a member of PLP-dependent amino acid racemases, and is distinct from alanine racemase (EC 5.1.1.1) and amino acid racemase with low substrate specificity (EC 5.1.1.10). This is the first report of the occurrence of serine racemase in eukaryotes producing D-serine.

Animals↗
PubMed1998

Peptidyl human heart chymase inhibitors. 2. Discovery of highly selective difluoromethylene ketone derivatives with Glu at P3 site.

Appropriate structural modification of the difluoromethylene ketone derivatives at both P3 and P' positions led us to the discovery of peptidyl human heart chymase inhibitor 12h which shows potent activity with Ki = 6 nM and high selectivity against closely related serine protease bovine alpha-chymotrypsin (chymotrypsin Ki = > 100 microM). Using the compound 12b, a docking study with human heart chymase was carried out to presume probable interactions.

Animals↗