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Biomedical subjects

T Yoshimura

Publications and source records attributed to T Yoshimura.

At least 361 records · Page 20Linked to original sources

Modulation of neutrophil influx in glomerulonephritis in the rat with anti-macrophage inflammatory protein-2 (MIP-2) antibody.

The role of the chemokine, macrophage inflammatory protein-2 (MIP-2), during anti-glomerular basement membrane (GBM) antibody (Ab) glomerulonephritis (GN) was studied. Rat MIP-2 cDNA had been cloned previously. Recombinant rat MIP-2 (rMIP-2) from Escherichia coli exhibited neutrophil chemotactic activity and produced neutrophil influx when injected into the rat bladder wall. By using a riboprobe derived from the cDNA and an anti-rMIP-2 polyclonal Ab, MIP-2 was found to be induced in glomeruli with anti-GBM Ab GN as mRNA by 30 min and protein by 4 h, with both disappearing by 24 h. The expression of MIP-2 correlated with glomerular neutrophil influx. A single dose of the anti-MIP-2 Ab 30 min before anti-GBM Ab was effective in reducing neutrophil influx (40% at 4 h, P < 0.01) and periodic acid-Schiff deposits containing fibrin (54% at 24 h, P < 0.01). The anti-rMIP-2 Ab had no effect on anti-GBM Ab binding (paired-label isotope study). Functional improvement in the glomerular damage was evidenced by a reduction of abnormal proteinuria (P < 0.05). These results suggest that MIP-2 is a major neutrophil chemoattractant contributing to influx of neutrophils in Ab-induced glomerular inflammation in the rat.

Amino Acid Sequence↗

Structure and function of beta 2-glycoprotein I: with special reference to the interaction with phospholipid.

beta 2-Glycoprotein I (beta 2-GPI) is a cofactor in the recognition of a phospholipid antigen, cardiolipin, by anticardiolipin antibodies in autoimmune diseases such as systemic lupus erythematosus. We examined the interaction of various forms of bovine beta 2-GPI, such as its intact form, desialylated form (Asialo beta 2-GPI), N-terminal domain (domain I) and the modified forms of beta 2-GPI and Asialo beta 2-GPI with nicks in their C-terminal domains (domain 5), with phospholipid liposomes under different conditions of pH and ionic strength. We found that at neutral pH and low ionic strength beta 2-GPI bound to liposome membranes containing cardiolipin with a dissociation constant (Kd) of 10(-8) M. Phosphatidylglycerol, phosphatidylserine, phosphatidic acid or phosphatidylinositol bound to beta 2-GPI, but phosphatidylcholine did not. We also found that domain I and Asialo beta 2-GPI bound to cardiolipin with Kd values of 10(-6) and 10(-8) M, respectively. At neutral pH and both low and high ionic strengths, the affinities of nicked forms of beta 2-GPI and Asialo beta 2-GPI for cardiolipin were lower than those of intact forms but similar to that of domain 1.

Amino Acids↗

Effect of theophylline on the production of interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-8 by human peripheral blood mononuclear cells.

Theophylline is a mild bronchodilator and has significant extrapulmonary effects, but it may also have some anti-inflammatory properties. We investigated the immunological effects of theophylline on peripheral blood mononuclear cells (PBMC), by examining the production of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin 8 (IL-8) when PBMC were stimulated with lipopolysaccharide (LPS) or recombinant human IL-1 beta (rhIL-1 beta). At concentrations > or = 50 micrograms/ml, theophylline suppressed the proliferative activity of PBMC stimulated with phytohemagglutinin (p < 0.05). IL-1 beta production showed 23% suppression by 10 micrograms/ml theophylline (p < 0.05), while the suppression was 26% at 25 micrograms/ml (p < 0.05), 30% at 50 micrograms/ml (p < 0.05), and 33% at 100 micrograms/ml (p < 0.05). TNF-alpha production was suppressed in a dose-dependent manner by theophylline, being decreased by 24% at 10 micrograms/ml (p < 0.05), by 29% at 25 micrograms/ml (p < 0.05), by 41% at 50 micrograms/ml (p < 0.01), and by 54% at 100 micrograms/ml (p < 0.01). IL-8 production, in contrast, was not affected by theophylline. rhIL-1 beta induced IL-8 production in a dose-dependent manner at concentrations of 1-100 units/ml, and theophylline (particularly at concentrations of 50 and 100 micrograms/ml), increased IL-8 production in the presence of rhIL-1 beta. Suppression of the production of IL-1 beta and TNF-alpha by therapeutic levels of theophylline suggested that this drug might have anti-inflammatory and immunosuppressive effects.

Anti-Inflammatory Agents, Non-Steroidal↗

Effects of roxithromycin on proliferation of peripheral blood mononuclear cells and production of lipopolysaccharide-induced cytokines.

Roxithromycin (RXM), a new macrolide antibiotic, has a 14-member macrocycline ring structure which is similar to that of erythromycin. We investigated the effects of RXM on the proliferation of peripheral blood mononuclear cells (PBMCs) and the production of interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha) by PBMCs stimulated with lipopolysaccharide (LPS). At concentrations greater than 25.0 micrograms/ml, RXM suppressed the proliferation of PBMCs stimulated with phytohemagglutinin, probably due to cytotoxicity. When the PBMCs were incubated with RXM for 7 d, the number of adherent cells (monocyte/macrophages) increased. Incubation with RXM at a concentration of 25.0 micrograms/ml induced the greatest increase (p < 0.05). IL-1 beta and TNF-alpha were present 3 h after LPS-stimulation, and IL-1 beta production reached a peak at 12 h and TNF-alpha production at between 6 and 12 h, and then their production declined. RXM (25 micrograms/ml) suppressed the production of IL-1 beta and TNF-alpha slightly during the entire course of the incubation. This suppression was dose-dependent. Anti-human granulocyte-macrophage colony-stimulating factor and anti-human macrophage colony stimulating factor antibodies had no effect on the RXM-induced proliferation of adherent cells. Suppression of the production of IL-1 beta and TNF-alpha by RXM suggested that this drug might have anti-inflammatory and immunosuppressive effects.

Anti-Bacterial Agents↗

Synthesis of 19-hydroxylated bile acids and identification of 3 alpha,7 alpha,12 alpha,19-tetrahydroxy-5 beta-cholan-24-oic acid in human neonatal urine.

The synthesis of 19-hydroxylated bile acids (3 alpha,19-dihydroxy-, 3 alpha,7 alpha,19-trihydroxy-, 3 alpha,12 alpha,19-trihydroxy- and 3 alpha,7 alpha,12 alpha,19-tetrahydroxy-5 beta-cholan-24-oic acids) was described. These synthesized 19-hydroxylated bile acids were used as standard samples for the analysis of bile acids in human urine by gas chromatography-mass spectrometry. 3 alpha,7 alpha,12 alpha,19-Tetrahydroxy-5 beta-cholan-24-oic acid was identified in neonatal urines (0.1-1.5 micrograms/ml and 1.5-7% of total bile acids).

Bile Acids and Salts↗

Expression of monocyte chemoattractant protein-1 in meningioma.

Monocyte chemoattractant protein-1 (MCP-1), purified from glioma cell line (U-105MG) culture fluid, attracts monocytes but not neutrophils. Macrophage accumulation is one of the pathological features of meningioma. To investigate the mechanism of macrophage infiltration into meningioma, the expression and localization of MCP-1 in 16 cases of meningioma were studied using Northern blot analysis and immunohistochemistry. Seven of 16 meningiomas expressed MCP-1 messenger ribonucleic acid and protein, and some degree of macrophage infiltration was seen in all 16 meningiomas. There was a relationship between MCP-1 expression and the degree of macrophage infiltration; MCP-1 was strongly expressed in meningiomas with a high degree of macrophage infiltration. Sometimes the meningioma was accompanied by perifocal edema; a correlation between macrophage infiltration into brain tumors and perifocal edema has already been reported. It was found that the degree of MCP-1 expression is not correlated with the extent of perifocal edema. The authors' findings suggest that MCP-1 plays an important role in macrophage infiltration into meningioma.

Adult↗

[The long-term results of isolated aortic valve replacement with 19 mm prostheses].

Twenty-five patients underwent isolated aortic valve replacement with 19 mm valves (8 cases with St. Jude Medical prostheses, 7 cases with Carpentier Edwards Pericardial prostheses and 10 cases with Björk-Shiley prostheses). Postoperative echocardiography revealed data as follows. Peak pressure gradients (mmHg) were 40.4 +/- 14.4 (mean +/- S.D.) in the SJM group, 23.4 +/- 9.8 in the CEP group and 50.5 +/- 16.7 in the BS group. End-diastolic left ventricular dimension in the BS group and interventricular septum thickness in the CEP group was reduced significantly. All but one case were in NYHA functional class I or II, and clinical improvement was almost satisfactory in all groups. However, in the BS group, 4 cases showed peak pressure gradients more than 50 mmHg. We conclude that 19 mm aortic prostheses in this study can provide satisfactory results. However, as for mechanical valve, it may be undesirable to choose BS prosthesis.

Adult↗

[A case of thromboexclusion for thoracic descending aortic pseudoaneurysm with Behçet's disease].

A 59-year-old woman with Behçet's disease was admitted because of hemoptysis. She had undergone resection and patch closure of a thoracic descending aortic aneurysm 6 years before this current admission. The aortography after the first operation had shown a pseudoaneurysm at the operative site. In the current operation, we performed thromboexclusion with a temporary occlusion balloon in the distal thoracic descending aorta above Adamkiewicz. The post operative course was uneventful. Postoperative angiography demonstrated exclusion of the pseudoaneurysm and the patient was discharged without recurrent hemoptysis.

Aneurysm, False↗

[Effects of polychlorinated biphenyls on regeneration of the peripheral nerve in rats].

The effects of polychlorinated biphenyls (PCB) on regeneration of the peripheral nerves were investigated in rats. The sciatic nerves were crushed at the mid-thigh level on the last day of 32 days of oral administration of PCB. The sciatic nerves were biopsied from the crushed regions at 1, 2, 4, 8 and 12 weeks after crushing. Myelin thickness on the axon diameter was smaller in the PCB administered group than in the control group. There was no difference between the experimental group and the control group in the density of regenerating fibers and distribution of fiber diameters in unmyelinated fibers. After 12 weeks the number of large diameter myelinated fiber densities was lower in the experimental group than in the control group. These results indicate that PCB may affect the remyelination of the regenerating nerve.

Animals↗

[Segmental muscular atrophy of unilateral upper limb associated with cervical disc herniation in a juvenile male].

A 25-year-old man first noticed atrophy of right upper arm at the age of 15. This symptom progressed for the following 3 years and then became stable. As he noted difficulty in elevating his right arm above the shoulder level, at the age of 25 he was admitted to our hospital. On neurological examination, he had right scapula alata, moderate atrophy and weakness of right triceps muscle. Right triceps reflex was absent. Other neurological examinations were normal. Needle electromyography revealed neurogenic patterns in the muscles of the C5-T1 segments. Cervical MRI and CT myelography revealed mild cervical disc protrusion toward the right side at the C5/6 level and atrophy of the middle and lower cervical cord on the right side, but nothing suggestive of the fexion myelopathy. The clinical manifestations of the patient resembled those of Hirayama disease, except for the distribution of the involved muscles. Since the most severely involved level of the cervical cord (C7 segment) corresponded to the level of the protruded cervical disc, it was suggested that the cervical disc herniation played an important role in the development of the myelopathy in this patient.

Adult↗

[Pseudoaneurysm of saphenous vein graft after CABG].

A 69-year-old man was admitted because of angina pectoris and thoracic descending aorta aneurysm. Staged operations were planned. First, he underwent CABG (coronary artery bypass grafting) with SVGs (saphenous vein grafts) to #4 PD, #7 and #12. Aprotinin was administrated to reduce blood loss. The routine postoperative graft angiography and enhanced CT showed a pseudoaneurysm in the SVG to #4 PD. We planned an elective operation of pseudoaneurysm repair and graft replacement of thoracic descending aorta. Also in this second operation, continuous infusion of aprotinin was started after the induction of anesthesia. About 30 minutes later, he suddenly fell in shock and cardiac arrest. Partial cardiopulmonary bypass was established and median sternotomy was performed. In the mediastinum, no bleeding was found. We found out a bleeding point of the SVG to #4 PD and a hemostatic clip on the right ventricule, and closed the bleeding point with suture. The cause of the pseudoaneurysm seemed to be defluxion of the hemostatic clip for a side brunch of the SVG. The cause of the preoperative shock may be an anaphylaxis to readministrated aprotinin.

Aged↗

Immunophenotypic and immunoelectron microscopic characterization of major constituent cells in malignant fibrous histiocytoma using human cell lines and their transplanted tumors in immunodeficient mice.

BACKGROUND: Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma of adult life. Its histogenesis, however, is still a matter of debate because of its various cellular components. EXPERIMENTAL DESIGN: To elucidate the nature of tumor cells of MFH, six human MFH cell lines were compared immunohistochemically and immunoelectron microscopically with fibrosarcoma and fibroblast cell lines. In vitro differentiation of tumor cells was evaluated after the treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA), IL-3, macrophage CSF, and granulocyte-macrophage CSF. Heterotransplantation of MFH tumor cells into nude mice and severe combined immunodeficient mice was performed to examine whether the tumor cells differentiate toward histiocytes or not. Gene expression of monocyte chemoattractant protein-1 in cultured tumor cells and transplanted tumors was also evaluated. RESULTS: All MFH cell lines examined were positive for collagen type I and prolyl hydroxylase. They failed to react with most anti-myeloid mAb such as CD11c, CD14, CD15, CD33, CD35, CD45, anti-HLA-DR, and PM-2K. Several Ab, including CD13, CD32, CD68, CD71, and HAM56, were reactive with MFH cells. However, all of these Ab were also reactive with fibrosarcoma and/or fibroblastic cell lines. These data indicate that MFH cell lines possess immunophenotypic characteristics very similar to those of fibrosarcoma and fibroblastic cell lines. In vitro treatment of tumor cells with TPA, IL-3, macrophage CSF, granulocyte-macrophage CSF, or their combination did not change their immunophenotypic characteristics and did not induce differentiation toward histiocytes (macrophages). Transplantation of tumor cells into nude mice and severe combined immunodeficient mice produced tumors similar in histology to human MFH. Tumor cells in the transplanted tumors revealed the same immunophenotypic characterization that they did in vitro. No in vivo differentiation of tumor cells toward histiocytes was observed. Immunohistochemical staining with anti-mouse macrophage mAb revealed marked infiltration of macrophages of mouse origin. Quantitative immunoelectron microscopy disclosed that these cells coincided with histiocyte-like cells. Gene expression of monocyte chemoattractant protein-1 was detected in all MFH cell lines as well as in transplanted tumors. CONCLUSIONS: The histiocyte-like cells in malignant fibrous histiocytoma are not a neoplastic component but rather infiltrated macrophages attracted by tumor-derived monocyte chemoattractant(s), and the tumor cells belong to a fibroblastic lineage differentiated from mesenchymal cells.

Adult↗

[Small bowel metastasis from large cell carcinoma of the lung: report of a case].

The case of a 44-year-old man with metastatic tumor of the small intestine from large cell carcinoma of the lung was reported. The patient underwent exploratory thoracotomy because of tumor invasion into the left ventricle. He was discharged from our department after chemotherapy and irradiation. However, he was again admitted because of the development of anemia secondary to melena. An abdominal ultrasonography revealed ascites and tumor of the small intestine. Symptoms of ileus also developed. A laparotomy was performed. The metastatic tumors were found in the jejunum, and resection of jejunum was performed. The postoperative course of the patient was uneventful, and he survived one month after laparotomy. Small bowel metastasis of lung cancer, which is unusual pattern of metastasis, is also reviewed.

Adult↗

[A case of hereditary pressure-sensitive neuropathy, confirmed by a gene analysis].

A 21-year-old male patient with hereditary pressure-sensitive neuropathy (HPSN) is reported. He had been well and was working as a carpenter until February 6, 1993, when he developed difficulty in raising his left arm and numbness in the radial aspect of his left forearm in the morning. Left musculocutaneous nerve palsy, a left winged-scapula, absence of the left biceps and right Achilles reflexes, and distal dominant nerve conduction delay were positive findings. His father and younger brother showed similar conduction delays. Sural nerve biopsy revealed the presence of tomacula, segmental demyelination and thinly myelinated fibers. Gene analyses of the patient's cultured lymphoblastoid cells disclosed deletion of the marker 6G1 and peripheral myelin protein-22 (PMP-22) gene of a single allele of chromosome 17 in 90% of his intermitotic cells by in situ hybridization, and also a 57% gene dosage of PMP-22 of normal control using Southern blotting. These findings indicate the deletion in 17p11.2 of the genomic DNA of this patient, which is diagnostic for HPSN.

Adult↗

[A family of X-linked motor and sensory neuropathy with a new type of connexin32 mutation].

A 28-year-old man had complaints of muscle weakness in both his legs and fingers. Moderate degrees of symmetrical atrophy adn weakness of the bilateral lower limbs, moderate degree of muscle atrophy was also noticed distal to the lower one third of the upper thigh. A moderate degree of weakness of the anterior tibial, extensor digitorum and peroneus muscles was also noted. Pes cavus deformity was evident bilaterally. Knee jerk was normal, and Achilles tendon reflex was absent without pathologic reflexes. He could not walk on his heels. Vibratory sensation was severely decreased in the toes, and both touch and pain sensations were slightly decreased on the dorsum of the feet. The median motor nerve conduction velocity was 28.9 m/sec with a prolonged distal latency. An amplitude of M-wave evoked by electrical stimulation of the median nerve 1 mV. No M-wave was obtained from stimulation of the tibial nerve, and no sensory nerve action potentials were elicited from electrical stimulation of the median and sural nerves. Histologic studies of the biopsied sural nerve revealed the occasional presence of internodes with a thin myelin sheath and a decrease in the density of large myelinated fibers. Small and atypical onion-bulbs were occasionally observed by electron microscopy. Based on the neurological examination and nerve conduction study of the family members, a sister, mother and grandmother of the proband were found to be mildly affected without any disability in their daily activities. However, the father and an uncle on the mother's side of the proband were normal. Therefore, we concluded clinically that this family had HMSN type I with autosomal dominant inheritance or X-linked HMSN. In the studies of fluorescence in situ hybridization and restriction fragment length polymorphism of the genomic DNA of the proband, a DNA duplication in chromosome 17p11.2-12 was not observed. A single-strand conformational polymorphism analysis of the genomic DNA encoding connexin32 (Cx32) revealed the abnormal band different from that of the control. A sequence analysis of the genomic DNA obtained by use of the polymerase chain reaction was also performed. It revealed that there was a mutant allele, a cytosine to thymine substitution of the nucleotide position 140, which caused a substitution of leucine for serine at amino acid position 26. The proband's mother was heterozygous for the mutant allele and the normal allele. This type of Cx32 mutation was different from any type of Cx32 mutation reported in the literature. The mutation in this family is located in the first transmembrane portion of Cx32, and may alter the function of Cx32 protein, as well as lead to the functional and structural abnormalities of the myelin sheath at the nodes of Ranvier and Schmidt-Lanterman's incisures, where Cx32 is present. This is the first Japanese X-linked HMSN family showing a new type of mutation of Cx32 gene with clinical findings and a histologic evaluation of the sural nerve.

Adult↗

[A Japanese family with paramyotonia congenita which has a mutation in the muscle sodium channel gene].

We report here a Japanese family with paramyotonia congenita. The proband was a 42-year-old woman (case 1), who noticed muscle stiffness and weakness in the cold since the age of 7 years. These symptoms were alleviated by warming. Her eldest son (case 2) also experienced similar symptoms, while her younger son and daughter were healthy. Neurological examination in case 1 revealed mild weakness in facial and neck muscles. Cold-induced muscle stiffness and weakness were present. Electromyography showed myotonic discharges, intensified by cooling or repetitive exercise. The amplitude of the compound muscle action potentials was also reduced by the repetitive exercise and cooling. Serum chemistry including potassium and CK was normal. Molecular analysis of SCN4A (exon22-24) by SSCP and nucleotide sequencing revealed a C-to-T transition at nucleotide 3,938, causing a substitution of 1313methionine of threonine in case 1. This mutation was confirmed by PCR-RFLP with a mismatched primer; the proband (case 1) and her eldest son (case 2) had a heterozygous mutation, while the other family members did not. This is the first report that a mutation in SCN4A was identified in a Japanese family with paramyotonia congenita.

Adult↗