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Biomedical subjects

T Yoshimura

Publications and source records attributed to T Yoshimura.

At least 235 records · Page 13Linked to original sources
PubMed1998

Cystothiazoles A and B, new bithiazole-type antibiotics from the myxobacterium Cystobacter fuscus.

New bithiazole-type antibiotics, cystothiazoles A (C20H26N2O4S2) and B (C20H26N2O5S2), have been isolated from a culture broth of the myxobacterium, Cystobacter fuscus. The gross structures of these compounds were elucidated by spectroscopic analysis, and their absolute stereochemistry was determined by chemical degradation of cystothiazole A. Cystothiazole A inhibits fungi and human tumor cells, whereas it is inactive against bacteria. The antifungal activity appears to result from the inhibition of submitochondrial NADH oxidation. Although these compounds are structurally related to the known antibiotic myxothiazol, cystothiazole A was more active against fungi and less cytotoxic than myxothiazol.

Anti-Bacterial Agents↗
PubMed1998

[A case of multiple sclerosis associated with myelin associated glycoprotein neuropathy].

A 28-year-old woman had developed chronic, recurrent, visual disturbance (bilateral), and girdle sensation at Th 5-6. She was admitted to our hospital because of left visual disturbance, distal limb weakness on right side, and numbness of four extremities. The neurological examination revealed decreased visual acuity of the left eye with abnormality of the optic disk, moderate muscle weakness of the right upper and lower extremities, absent tendon reflexes and paresthesia on distal portions of the four limbs. Laboratory examinations disclosed the titration of anti-myelin associated glycoprotein (MAG) antibody (IgM) and CSF protein was elevated (104 mg/dl). Motor nerve conduction studies revealed conduction block in more than one nerve. The conduction velocities in the upper and lower extremities were all diminished. P100 latency was prolonged by flash visual evoked potential (VEP) studies. N13-N20 interpeak latency of somatosensory evoked potential (SEP) of median nerve was also prolonged. She was treated with steroid pulse therapy, followed by an oral dose of 30 mg/day of prednisolone. Her symptoms resolved completely three months later, and multifocal conduction block subsided on electrophysiological study. There are some cases of multiple sclerosis with multifocal conduction block, but such a case is very rare in Japan. We discussed the pathogenic mechanisms of these conditions, and we conclude that we must take notice of demyelinating neuropathy in multiple sclerosis and that nerve conduction studies are useful for detecting them.

Adult↗
PubMed1998

Effects of a nitric oxide synthase inhibitor on pressor response to angiotensin II in conscious rats.

OBJECTIVE: We sought to characterize the effects of NG-monomethyl-L-arginine (L-NMMA) and L-arginine (L-Arg) on the pressor response to the infusion of angiotensin II in rats. METHODS: L-NMMA and L-Arg were infused intraperitoneally into rats at a constant rate by means of an osmotic minipump. The L-NMMA group received an infusion of L-NMMA (3 mg/d) daily for 13 d, whereas the L-NMMA plus L-Arg group received L-NMMA (3 mg/d) daily for 4 d, followed by L-NMMA plus L-Arg (12 mg/d) daily for 9 d. Sham operated rats served as controls. The animals were anesthetized on day 13, and catheters were placed into the femoral artery and vein. After the animals had recovered from the anesthesia, the pressor response to intravenous bolus doses of angiotensin II (50, 100, 200, and 400 ng/kg) were determined after recovery from anesthesia. RESULTS: While the baseline mean arterial blood pressure was not affected by L-NMMA, with or without L-Arg, the pressor response to angiotensin II in the L-NMMA group was significantly increased as compared with that in the control group, at doses of 50, 100, and 200 ng/kg. The response of the L-NMMA plus L-Arg group did not differ significantly from that of the control group. CONCLUSION: Results indicate that the infusion of a nitric oxide synthase inhibitor, at a dose insufficient to produce hypertension, increases the pressor response to angiotensin II.

Acetylglucosaminidase↗
PubMed1998

Analysis of the cytokine network among tumor necrosis factor alpha, interleukin-1beta, interleukin-8, and interleukin-1 receptor antagonist in monosodium urate crystal-induced rabbit arthritis.

In the present study, we analyzed the cytokine network among TNFalpha, IL-1beta, IL-8, and IL-1 receptor antagonist (IL-1Ra) in a rabbit experimental model of acute gout. The production of TNFalpha in synovial fluids reached the peak at 2 hours after the intra-articular injection of monosodium urate (MSU) crystals. The production of IL-1beta and IL-8 reached the first peak at 2 hours and the second peak at 9 and 12 hours, respectively. The production of endogenous IL-1Ra reached the peak at 9 hours. The source of TNFalpha and the first phase of IL-8 was synovial cells, whereas infiltrating leukocytes were the source of the second phase of IL-8 and also of IL-1beta and IL-1Ra. The production of TNFalpha was not altered by either anti-lL-8 IgG or IL-1Ra. The first IL-1beta peak was reduced only with a combination of anti-TNFalpha mAb and anti-lL-8 IgG, whereas the second peak was significantly reduced by either inhibitor. The first IL-8 peak was not altered with anti-TNFalpha mAb or IL-1 Ra, whereas the second IL-8 peak was reduced with IL-1Ra. Anti-TNFalpha mAb or anti-lL-8 IgG significantly reduced the peak level of endogenous IL-1Ra. These cytokine inhibitors also attenuated the maximal leukocyte accumulation at 9 hours, but not the initial phase, which occurred within 2 hours. These results provide evidence that IL-8 and TNFalpha were responsible for the production of IL-1beta and IL-1Ra, and that IL-1beta was responsible for the second phase of IL-1beta and IL-8 production. Our data also suggest that the initial and the maximal phases of leukocyte influx are differently regulated. Finally, the intravenous injection of colchicine inhibited neutrophil infiltration without affecting the production of TNFalpha or the first peak of IL-8, suggesting that colchicine inhibits MSU crystal-induced arthritis by directly inhibiting the migration of neutrophils.

Animals↗
PubMed1998

[Quantitative analysis of telomerase activity in exfoliated urothelial cells for the diagnosis of bladder carcinoma].

Voided urine cytology is the most common non-invasive examination for the detection and monitoring of bladder cancer. However, the result is not satisfactory, especially for low grade tumors. Activity of telomerase can be detected in most tissues of bladder carcinoma using the telomeric repeat amplification protocol (TRAP) assay. We analyzed the quantitative telomerase activity in exfoliated urothelial cells, and evaluated the values for early diagnosis of bladder carcinoma. We performed a quantitative analysis using a hybridization protection assay (HPA) based on TRAP assay. Telomerase activity was significantly higher level in exfoliated urothelial cells from patients with bladder cancer than all of healthy cases and patients with benign disease (p < 0.0001). The cut off value was calculated as mean + 2SD of the telomerase activity level of the exfoliated urothelial cells from healthy cases. Using this cut off value, telomerase activity was positive in 26 of 41 in exfoliated urothelial cells from bladder cancer patients(63.4% sensitivity), and negative in 63 of 69 in exfoliated urothelial cells from healthy cases and patients with benign disease (91.3% specificity). The sensitivity of telomerase activity in exfoliated cells was higher than urinary cytology, especially in low grade tumors. Our results indicate that quantitative analysis of telomerase activity in exfoliated urothelial cells could become minimum invasive and useful method for detection of bladder carcinoma.

Humans↗
PubMed1998

Subacute multifocal painful neuropathy with spontaneous remission.

We present the cases of two patients with subacute onset of multifocal painful neuropathy with spontaneous remission and no relapse. The distribution of pain in patient 1 was hands (median > ulnar nerve region) and feet (peroneal and terminal tibial nerve regions), and in patient 2, hands (ulnar nerve region) and feet, left worse than in right. Both patients experienced facial numbness. Deep tendon reflexes were intact except for absent ankle jerks in patient 2. Motor nerve conduction studies demonstrated a marked prolongation of the distal motor latencies with normal proximal segment conduction velocities, suggesting distal demyelination. Cerebrospinal fluid protein concentration was elevated in patient 2, but no definite abnormality was found on sural nerve biopsy. A demyelinating neuropathy with a monophasic self-limited course may be consistent with Guillain-Barre syndrome (GBS). However, the multifocal painful sensory symptoms with facial numbness and the marked distal nerve conduction slowing in our cases are not consistent with GBS.

Adult↗
PubMed1998

Production and regulation of monocyte chemoattractant protein-1 in lipopolysaccharide- or monosodium urate crystal-induced arthritis in rabbits: roles of tumor necrosis factor alpha, interleukin-1, and interleukin-8.

The production of monocyte chemoattractant protein-1 (MCP-1) and its regulation by TNFalpha, IL-1, and IL-8 were investigated in two rabbit models of arthritis induced by intra-articular injection of lipopolysaccharide (LPS) or monosodium urate (MSU) crystals. We first prepared recombinant rabbit MCP-1 and antibodies and then developed an immunoassay. The immunoassay detected 3 pg/ml rabbit MCP-1 and did not cross-react with other rabbit chemokines such as IL-8 or GRO. MCP-1 was first detected in synovial fluid (SF) at 1 hour, and peaked at 4 or 2 hours after the injection of LPS or MSU crystals, respectively. Immunohistochemically, MCP-1 was detected in synovial lining cells and infiltrating neutrophils. The amounts of MCP-1 detected in SF from neutrophil-depleted rabbits were similar to those in normal rabbits, suggesting that synovial lining cells were the main source of MCP-1 detected in SF. The peak level of MCP-1 in SF after LPS-injection was inhibited by 57% with anti-TNFalpha mAb and by 41% with IL-1 receptor antagonist (IL-1Ra). Coadministration of anti-TNFalpha mAb and IL-1Ra inhibited 90% of MCP-1 production. In contrast, the peak level of MCP-1 in SF after MSU crystal-injection was not affected by any cytokine inhibitor, but was reduced by 52% with coadministration of anti-TNFalpha mAb and IL-1Ra. Anti-IL-8 IgG had no effect on the production of MCP-1 in either model. Thus, the production of MCP-1 in LPS-induced arthritis was mostly regulated by TNFalpha and IL-1, whereas half the extent of MCP-1 production in MSU crystal-induced arthritis was independent of TNFalpha or IL-1. IL-8 does not seem to regulate the production of MCP-1 in SF either directly or indirectly. Finally, administration of neutralizing anti-MCP-1 antibody inhibited LPS- and MSU crystal-induced monocyte infiltration by 58.4% and 44.9%, respectively, suggesting that synovial production of MCP-1 plays an important role in the recruitment of monocytes in these arthritis models.

Animals↗
PubMed1998

[Persistent lateral gaze palsy and abducens nerve palsy due to pontine infarction].

A 76-year-old hypertensive man noticed sudden dizziness and diplopia. On examination, right-sided gaze deviation was present, but the remainder of the neurological examination was normal. Five days later, MRI revealed a small lesion in the left paramedian pontine tegmentum, which was consistent with pontine infarction. The conjugate deviation disappeared about two weeks after the onset, but a left lateral gaze and abducens nerve palsy have persisted at ten months after the infarct. MRI findings are unchanged. The site of infarction is presumed to be located in the caudal portion of paramedian reticular formation and the abducens nerve fascicle. Persistent lateral gaze palsy is rare in pontine infarction, and this case is important in illustrating the anatomical location of paramedian pontine reticular formation.

Abducens Nerve↗
PubMed1998

Respiratory Difficulty Necessitated Early Delivery in a Woman with Spondyloepiphyseal Dysplasia.

> Spondyloepiphyseal dysplasia is a skeletal disorder in which the vertebrae are flattened, thus making the spine shorter and greatly deformed, with marked thoracic kyphoscoliosis, lumbar lordosis, and a shortened trunk. The pelvis is also severely deformed and contracted. The patient was a 40-year-old nulligravida. At the 33rd week of pregnancy, respiratory distress gradually worsened, and cesarean section under spinal anesthesia had to be done. In women with spondyloepiphyseal dysplasia, uterine expansion is limited. As respiratory difficulties increase, an early delivery may have to be done.

Journal Article↗
PubMed1998

[A case of Salmonella subdural empyema developed in chronic subdural hematoma].

A case of Salmonella subdural empyema developed in chronic subdural hematoma (Infected Subdural Hematoma; ISH) was reported. A 64-year-old man had been in a nearby hospital due to myelodysplastic syndrome with cerebral infarction for two months. His condition there had been almost uneventful. But spike fever occurred and the patient became drowsy two days before his transfer to our medical center. His consciousness level deteriorated progressively and CT scan showed a right chronic subdural hematoma. He had had no history of head trauma in the previous two months. On admission to our center, his consciousness level was semicoma with anisocoria. An emergency operation was performed via a single burr hole initially. From the burr hole, old bloody fluid accompanied by yellowish pus was obtained. Thus so-called ISH was diagnosed and the craniotomy was carried out. Gram stain of the specimen revealed gram negative rods. Although an epileptic state developed after the operation, it was controlled by barbiturate coma therapy for 3 days, followed by phenytoin administration. Fever subsided gradually with antibiotics sensitive to the bacteria and his anisocoria disappeared on the 4th postoperative day. In this case, Salmonella enteritidis was detected from bacterial culture both of the specimen and of the arterial blood. Salmonella enteritidis might have been implanted on the capsule of the chronic subdural hematoma by bacteremia derived from immunological dysfunction due to myelodysplastic syndrome. In conclusion, the possibility of ISH should be considered in chronic subdural hematoma patients with immunological dysfunction.

Chronic Disease↗
PubMed1998

[A case of cervical radiation radiculopathy resembling motor neuron disease].

A 67-year-old man developed slowly progressive muscular weakness in the bilateral upper extremities (C5- 7 regions) without signs of sensory deficit following the cervical radiation therapy (70.5Gy) for right laryngeal cancer 4 years before. These clinical signs resembled those of lower motor neuron disease. MRI with gadolinium-DTPA, however, showed enhancement in the bilateral C5 and C6 anterior roots, suggesting the cervical radiculopathy due to radiotherapy. It is known that radiation to the spinal cord can lead to "selective anterior horn cell injury". This is the first case report of the cervical radiation radiculopathy, which, if without MRI, might be classified into selective anterior horn cell injury. Suggestion is made for the hypothesis that the spinal motoneuron loss in radiation myelopathy would be caused by retrograde degeneration due to anterior root damages.

Aged↗
PubMed1998

New method to measure telomerase activity by transcription-mediated amplification and hybridization protection assay.

Telomerase is a ribonucleoprotein complex that uses RNA as a template for the addition of telomeric repeats. The development of the telomeric repeat amplification protocol (TRAP), a sensitive PCR-based assay, has facilitated the detection of telomerase activity in small tissue and tumor samples. Telomerase activity is expected to be a new diagnostic and prognostic marker of human cancer. In this study, we applied a non-PCR-based transcription-mediated amplification (TMA) and hybridization protection assay (HPA) to the measurement of telomerase activity by modification of both primers in TMA. We demonstrated that the modified TMA can detect and measure telomerase activity. TMA/HPA is as sensitive and reproducible as conventional TRAP, but is both faster and easier to perform. Furthermore, we found that TMA/HPA was influenced minimally by TRAP inhibitors that may come from clinical samples. TMA/HPA, which is easy, rapid, and applicable to a high-throughput format, should be clinically useful for the detection and monitoring of telomerase activity.

Carcinoma, Hepatocellular↗
PubMed1997

Induction of the S100 chemotactic protein, CP-10, in murine microvascular endothelial cells by proinflammatory stimuli.

Microvascular endothelial cells (EC) have multiple functions in inflammatory responses, including the production of chemoattractants that enhance leukocyte transmigration into tissues. Chemotactic protein, 10 kD (CP-10), is an S100 protein with potent chemotactic activity for myeloid cells in vitro and in vivo and is expressed in neutrophils and lipopolysaccharide (LPS)-activated macrophages. We show here that CP-10 is induced in murine endothelioma cell lines (bEnd-3, sEnd-1, and tEnd-1) after activation with LPS and interleukin-1 (IL-1) but not tumor necrosis factor alpha (TNFalpha) or interferon gamma (IFNgamma). Induction was not mediated by endogenous release of IL-1 or TNFalpha and was not directly upregulated by phorbol myristate acetate, calcium ionophore, or vitamin D3. EC were exquisitely sensitive to IL-1 activation (3.4 U/mL) and CP-10 mRNA induction with IL-1 occurred earlier (8 hours) than with LPS (12 hours). Furthermore, some microvessels and capillaries in delayed-type hypersensitivity lesions expressed cytoplasmic CP-10. Responses to LPS and not IL-1 in vitro were regulated by the degree of cell confluence and by TNFalpha costimulation. The related MRP-14 mRNA had a different induction pattern. Monomeric and homodimeric CP-10 upregulated by activation was predominantly cell-associated. EC-derived CP-10 may contribute to amplification of inflammatory processes by enhancing leukocyte shape changes and transmigration in the microcirculation.

Animals↗
PubMed1997

Transcriptional regulation of the human monocyte chemoattractant protein-1 gene. Cooperation of two NF-kappaB sites and NF-kappaB/Rel subunit specificity.

Human monocyte chemoattractant protein-1 (human MCP-1) mRNA accumulated in THP-1 cells 2 h after lipopolysaccharide (LPS) stimulation. DNase I footprinting revealed that LPS stimulation induced protein binding to the two closely located NF-kappaB sites, A1 and A2. By electrophoretic gel mobility shift assay and supershift assay, the binding of (p65)2, c-Rel/p65, p50/p65, and p50/c-Rel to the A2 oligonucleotide probe was detected after LPS stimulation. In contrast, 12-o-tetradecanoylphorbol 13-acetate did not induce a significant amount of MCP-1 mRNA in THP-1 cells 2 h after stimulation, and only p50/p65 bound to the A2 probe. trans-Activity of each NF-kappaB/Rel dimer was investigated by transfecting P19 cells with p65, p50, and/or c-Rel expression vectors, and a luciferase construct containing the enhancer region of the human MCP-1 gene. Expression of recombinant p65 or p65 and c-Rel resulted in elevated luciferase activities, indicating that (p65)2 and c-Rel/p65 had trans-activity. The binding of (p65)2 and/or c-Rel/p65 to the A2 probe was also detected from 12-o-tetradecanoylphorbol 13-acetate-stimulated HeLa, HOS, and A172 cells in which expression of MCP-1 mRNA was elevated. Finally, the role of the A1 site was investigated. Both (p65)2 and c-Rel/p65 bound to the A1 probe by electrophoretic mobility shift assay and a mutation in the A1 or A2 site resulted in a loss of the enhancer activity. These results suggest that the binding of (p65)2 and c-Rel/p65 to the A1 and A2 sites of this gene is important for the tissue- and stimulus-specific transcription of the human MCP-1 gene.

Base Sequence↗
PubMed1997

Successful application of pentoxifylline in the treatment of HTLV-I associated myelopathy.

Fifteen patients with human T-cell lymphotropic virus type-I (HTLV-I)-associated myelopathy (HAM) were treated in an uncontrolled preliminary trial by oral administration of pentoxifylline (PTX). Motor function, neurological evaluation, immunological markers and parameters were evaluated after four weeks. In 13 of the 15 patients, motor disability, especially spasticity, improved substantially. PTX suppressed spontaneous proliferation of peripheral blood mononuclear cells in 14 of the 15 patients at four weeks. No adverse effect was observed. We concluded that PTX may be a safe and beneficial agent for the treatment of HAM.

Adult↗
PubMed1997

Cysteine sulfinate desulfinase, a NIFS-like protein of Escherichia coli with selenocysteine lyase and cysteine desulfurase activities. Gene cloning, purification, and characterization of a novel pyridoxal enzyme.

Selenocysteine lyase (EC 4.4.1.16) exclusively decomposes selenocysteine to alanine and elemental selenium, whereas cysteine desulfurase (NIFS protein) of Azotobacter vinelandii acts indiscriminately on both cysteine and selenocysteine to produce elemental sulfur and selenium respectively, and alanine. These proteins exhibit some sequence homology. The Escherichia coli genome contains three genes with sequence homology to nifS. We have cloned the gene mapped at 63.4 min in the chromosome and have expressed, purified to homogeneity, and characterized the gene product. The enzyme comprises two identical subunits with 401 amino acid residues (Mr 43,238) and contains pyridoxal 5'-phosphate as a coenzyme. The enzyme catalyzes the removal of elemental sulfur and selenium atoms from L-cysteine, L-cystine, L-selenocysteine, and L-selenocystine to produce L-alanine. Because L-cysteine sulfinic acid was desulfinated to form L-alanine as the preferred substrate, we have named this new enzyme cysteine sulfinate desulfinase. Mutant enzymes having alanine substituted for each of the four cysteinyl residues (Cys-100, Cys-176, Cys-323, and Cys-358) were all active. Cys-358 corresponds to Cys-325 of A. vinelandii NIFS, which is conserved among all NIFS-like proteins and catalytically essential (Zheng, L., White, R. H., Cash, V. L., and Dean, D. R. (1994) Biochemistry 33, 4714-4720), is not required for cysteine sulfinate desulfinase. Thus, the enzyme is distinct from A. vinelandii NIFS in this respect.

Amino Acid Sequence↗
PubMed1997

Recombinant guinea pig and human RANTES activate macrophages but not eosinophils in the guinea pig.

To characterize the biologic activities of potential mediators of allergic inflammation, we have cloned, expressed, and purified guinea pig RANTES (gpRANTES). cDNA for gpRANTES was cloned from Con A-stimulated guinea pig spleen cells. A high level of gpRANTES expression in Escherichia coli was achieved by mutation of a human RANTES (hRANTES) expression construct to obtain a 68-amino acid protein identical with the predicted guinea pig amino acid sequence, assuming an equivalent amino terminus as the human protein. Purified gpRANTES was an effective stimulus of human eosinophils as assessed by increases in intracellular free calcium in fura-2-loaded cells and chemotactic responses in vitro. gpRANTES exhibits similar potency and efficacy to hRANTES. In marked contrast, neither gpRANTES nor hRANTES was able to activate guinea pig peritoneal eosinophils in these assays, even in the presence of IL-5. However, gpRANTES was found to be a potent stimulator of guinea pig peritoneal macrophages. Following tracheal instillation of gpRANTES, a dose-dependent increase in macrophages, but not eosinophils, was observed in gpBAL. Macrophage accumulation was detectable by 6 h and sustained for at least 48 h. These results indicate that RANTES in the guinea pig may have a different cellular selectivity than that described in the human, which may be important in the use of animal models in the analysis of allergic disorders. These selectivities do not appear to be accounted for by differences in guinea pig and human RANTES sequences.

Amino Acid Sequence↗