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Biomedical subjects

M Tsuboi

Publications and source records attributed to M Tsuboi.

At least 91 records · Page 5Linked to original sources
PubMed1996

Inhibitory effect of clarithromycin on costimulatory molecule expression and cytokine production by synovial fibroblast-like cells.

This study was undertaken to investigate the immunomodulatory effect of clarithromycin against synovial fibroblast-like cells (synoviocytes). Synovial tissue obtained from rheumatoid arthritis (RA) or osteoarthritis (OA) patients was enzymatically digested to separate synoviocytes. The synoviocytes were cultured with or without cytokines in the presence of various concentrations of clarithromycin. The expression of costimulatory molecules was examined on the surface of the synoviocytes, using specific MoAbs and flow cytometry. The production of cytokines by synoviocytes was also measured using an immunoenzymatic assay. Finally, autologous T cells were stimulated by interferon-gamma (IFN-gamma)-treated synoviocytes in response to purified protein derivative (PPD). In some experiments, MoAbs specific for costimulatory molecules or clarithromycin were added and 3H-thymidine incorporation was counted. Intercellular adhesion molecule-1 (ICAM-1), LFA-3 and vascular cell adhesion molecule-1 (VCAM-1) were detected on the surface of both RA and OA synoviocytes. However, ICAM-2, B7-1 and B7-2 were not detected, and cytokines failed to induce these molecules. Both spontaneous and up-regulated expression of ICAM-1, LFA-3 and VCAM-1 by IFN-gamma, IL-1beta or 12-o-tetradecanoyl phorbol 13-acetate (TPA) were markedly suppressed by clarithromycin in a dose-dependent manner at concentrations between 0.1 and 10 microg/ml. The production of IL-1beta, IL-6, IL-8, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) but not IL-1alpha and tumour necrosis factor-alpha (TNF-alpha) by synoviocytes was detected. Clarithromycin significantly suppressed the production of these cytokines, but did not enhance IL-10 production. Finally, autologous T cells were stimulated by IFN-gamma-treated synoviocytes in response to PPD. As clarithromycin suppressed HLA-DR and costimulatory molecule expression was enhanced by IFN-gamma, autologous T cell proliferation was markedly inhibited by clarithromycin. Clarithromycin has a considerable immunosuppressive effect on synoviocytes by inhibiting costimulatory molecule expression, cytokine production and antigen-specific T cell proliferation induced by synoviocytes.

Anti-Bacterial Agents↗
PubMed1996

The effects of the immunosuppressant rapamycin on the growth of rheumatoid arthritis (RA) synovial fibroblast.

RA is a chronic inflammatory disease characterized by mononuclear cell infiltration and the overgrowth of synovial fibroblast. This invasive growth of synovial tissues corresponds with the progressive destruction of articular cartilage and bone. Several immunosuppressive agents, such as cyclophosphamide, cyclosporin A and mizoribine, have been clinically used to control disease progression, though relatively little is known of their effects on rheumatoid synovium. Rapamycin exhibits a strong immunosuppressive activity by acting on T cell signalling pathways. In the present study we examined the effects of rapamycin on the growth of synovial fibroblast isolated from RA patients. Platelet-derived growth factor (PDGF) is a potent growth factor in synovial fibroblasts isolated from RA patients. PDGF and serum stimulation resulted in a rapid phosphorylation of tyrosine and activation of mitogen-activated protein kinase (MAP kinase), 70-kD-S6 kinase (P70S6k) and 90-kD-S6 kinase (P90rsk). Rapamycin, a macrolide immunosuppressant, inhibited completely growth factor-induced synovial fibroblast proliferation and P70S6k activation. In contrast, tyrosine phosphorylation and activation of MAP kinases and P90rsk were not influenced by rapamycin treatment. Our data demonstrate that growth factor-mediated P70S6k activation is closely related to the growth of synovial fibroblast, and suggest the efficacy of rapamycin for controlling synovial hyperplasia in RA.

Arthritis, Rheumatoid↗
PubMed1996

Thyroid-stimulating hormone inhibits Fas antigen-mediated apoptosis of human thyrocytes in vitro.

The mechanisms of TSH-induced growth stimulation of thyrocytes in vivo have yet to be elucidated. We examined the antiapoptotic effect of TSH toward Fas antigen-mediated apoptosis of thyrocytes. Fas antigen was expressed on approximately 40% of unstimulated thyrocytes, and the expression was significantly inhibited by the addition of TSH in a dose-dependent manner. Treatment of thyrocytes with 8-bromo-cAMP mimicked the effect of TSH, suggesting that the inhibitory effect of TSH on Fas antigen expression was mediated by activating protein kinase A. In contrast, treatment of thyrocytes with either interleukin-1 beta (IL-1 beta) or interferon- gamma (IFN gamma) markedly increased Fas antigen expression on thyrocytes, and these effects were inhibited in the presence of TSH. The expression of the protooncogene product Bcl-2 did not change after the addition of TSH, 8-bromo-cAMP, IL-1 beta, IFN gamma, or a combination of TSH and IL-1 beta or IFN gamma. When thyrocytes stimulated with either IL-1 beta or IFN gamma were treated with anti-Fas IgM mAb, the cells were committed to apoptosis, whereas this apoptotic process was significantly inhibited by the addition of TSH. These results indicate that the Fas antigen is functionally expressed on the surface of thyrocytes, and TSH inhibits Fas antigen-mediated apoptosis of thyrocytes through the inhibitory effect of Fas antigen expression, resulting in the promotion of growth of the thyroid gland.

Antibodies, Monoclonal↗
PubMed1996

Lack of B7-1/BB1 and B7-2/B70 expression on thyrocytes of patients with Graves' disease. Delivery of costimulatory signals from bystander professional antigen-presenting cells.

We have previously demonstrated that thyrocytes from patients with Graves' disease induce autologous peripheral blood T cell proliferation in response to soluble antigens, and a synergistic augmentation of T cell response by adding suboptimal numbers of monocytes. In the present study, we examined the role of costimulatory molecules, expressed on the surface of thyrocytes and intrathyroidal mononuclear cells, in antigen-specific T cell proliferation. Intercellular associated molecule (ICAM)-1 and lymphocyte function associated antigen-3 were constitutively expressed on the surface of both normal and Graves' thyrocytes. However, ICAM-2, vascular cell adhesion molecule-1, B7-1, and B7-2 were not detected and induced by cytokines. B7-1, was expressed on intrathyroidal monocytes only, while B7-2 was present on intrathyroidal lymphocytes, peripheral blood monocytes, and intrathyroidal monocytes. Furthermore, the density of B7-2 was higher on intrathyroidal monocytes than on peripheral blood monocytes. The intensity of CD28 expression on intrathyroidal CD8bright+ cells was less than that on peripheral blood CD8bright+ cells. The antigen-specific T cell response induced by thyrocytes was blocked completely by anti-human leukocyte antigen-DR monoclonal antibody (mAb) and partially by anti-ICAM-1 mAb and anti-lymphocyte function associated antigen-3 mAb. Furthermore, the synergistic augmentation of T cell response, induced by the addition of suboptimal number of monocytes, was suppressed completely by combining anti-B7-1 mAb and anti-B7-2 mAb, to a level equivalent to that observed when thyrocytes were used alone as antigen-presenting cells. Our results suggest that T cell proliferation was induced by cooperation of thyrocytes and infiltrating professional antigen-presenting cells.

Antigen Presentation↗
PubMed1996

A new type of familial central diabetes insipidus caused by a single base substitution in the neurophysin II coding region of the vasopressin gene.

We studied the genetic basis of familial neurohypophyseal diabetes insipidus in a Japanese family. The members had polyuria and a deficiency of plasma vasopressin (AVP). Polymerase chain reaction (PCR) amplified exons of the AVP-neurophysin-II gene were subcloned and sequenced. Exons 1 and 3 were normal, but nucleotide 1884 Guanine (G) in exon 2 was substituted with Thymine (T), which induced a substitution of glycine (Gly) for valine (Val). To examine the presence of this mutation in the affected subjects, we designed two mutated primers. One of them induced a new endonuclease restriction site in the PCR fragments from normal, and the other induced a new endonuclease restriction site from patients with the mutation. DNA fragments from two affected members of this family were amplified with this primer, and the PCR products were digested by endonuclease and resolved by electrophoresis. The results indicated that these subjects had both normal and mutant alleles, indicating that the mutation was heterozygous. We concluded that this mutation caused neurohypophyseal diabetes insipidus in this family.

Arginine Vasopressin↗
PubMed1996

Renal handling of urate in a patient with familial juvenile gouty nephropathy.

We encountered a case of familial juvenile gouty nephropathy (FJGN) with an autosomal dominant transmission pattern. Hyperuricemia in the propositus was caused by renal underexcretion of urate although his erythrocyte purine enzyme was normal. A renal biopsy specimen from the propositus showed interstitial fibrosis with tubular atrophy. On pyrazinamide and probenecid tests, the tubular secretion of urate selectively decreased without changes in either presecretory or postsecretory reabsorption of urate when his renal function was normal. Probenecid increased the urinary urate excretion and Cur/Ccr. The serum urate concentration was poorly controlled by allopurinol. When his renal function deteriorated, the uricosuric effects of both probenecid and benzbromarone were attenuated. However, the combined administration of probenecid with allopurinol decreased the serum urate concentration. These data suggest that the tubular secretion of urate is selectively impaired in FJGN and at the stage of renal failure, the combination of an uricosuric agent with allopurinol might be effective in treating hyperuricemia in FJGN.

Adolescent↗
PubMed1996

[Untoward effects of low dose methotrexate therapy in rheumatoid arthritis].

Sixty patients with rheumatoid arthritis who were administered weekly low dose methotrexate (MTX) were retrospectively analyzed for their untoward effects of MTX by interviewing to the patients and by the medical records. Cough and sputa were the most frequent symptoms (23.3%) and gastrointestinal symptoms were the next (20%). Five of 60 patients (8.2%) showed liver function test abnormalities, and four (6.7%) exhibited transient exacerbation of arthralgia for several hours to a few days after MTX administration. Three patients (5%) suffered from interstitial pneumonitis. Hair loss was seen in 3 patients (5%), and headache, leucocytepenia, fever, skin eruption, abnormal taste, hemorrhagic cystitis, and flashing were experienced in a patient, respectively. Three (5%) suffered from fungal infection, and herpes zoster, sepsis, and osteomyelitis were experienced in each one patient, respectively. MTX was withdrawn in three patients (5%) because of cough and sputa the drug was withdrawn in other three patients because of the interstitial pneumonia, and was drawn in another three patients because of transient exacerbation of arthralgia. The drug was withdrawn in each one patient, because of nausea and vomiting, skin eruption, osteomyelitis, and sepsis, respectively. Overall, MTX were withdrawn in 21 patients (35%), and, of those, 13 patients (21.7%) because of untoward effects and 8 patients (13.3%) because of the lack of efficacy.

Adult↗
PubMed1996

[Early lung cancer].

The number of patients with early lung cancer, which is detected by screening high risk group for lung cancer using sputum cytology, or by screening using CT is increasing. Recent studies have shown that some histologic types of early peripheral adenocarcinoma have no lymph node involvement. In addition, the incidence of multicentricity of peripheral type of early adenocarcinoma, detected by meticulous evaluation of CT images, is not so low. Video-assisted limited resection may be feasible in such cases. In spite of the excellent results of surgical resection for the hilar type of early lung cancer, surgery is at risk in some patients because of underlying pulmonary dysfunction and of a high incidence of second primary lung cancers. Endoscopic photodynamic therapy or brachytherapy may be an alternative to surgery as standard treatment in selected cases.

Cytodiagnosis↗
PubMed1996

[Renal hypouricemia].

Renal hypouricemia (serum urate < 2.0 mg/dl) is the inborn disorder due to the impaired tubular urate transport resulted in an increased urate excretion. The inheritance shows an autosomal recessive trait. The prevalence of renal hypouricemia is 0.15% in the outpatients. Based on the 4-component model, by using the pharmacological inhibitor, renal hypouricemia is classified into the 4 types as follows, 1) defective presecretory reabsorption, 2) defective postsecretory reabsorption, 3) enhanced urate secretion, and 4) both defective presecretory and postsecretory reabsorption including the three subtypes. Although renal hypouricemia has asymptomatic as usual, acute renal failure and urolithiasis (hematuria) have been reported as the complication. We further introduced the novel pathophysiology of the renal hypouricemia such as the aciduria correlating to the accelerated urate excretion and the hyperoxipurinemia in this review.

Acute Kidney Injury↗
PubMed1995

Expression of a cell adhesion molecule, neuropilin, in the developing chick nervous system.

Neuropilin (previously known as the A5 protein) is a membrane protein identified in Xenopus and is presumed to be involved in the target recognition of the optic nerve fibers. We have isolated cDNAs encoding the chick homologue of neuropilin, using the Xenopus neuropilin cDNA as a hybridization probe. The predicted amino acid sequence of chick neuropilin is 75% identical to that of the Xenopus homologue. A cell aggregation assay showed that fibroblasts transfected with the chick neuropilin cDNA acquired cell adhesiveness. This adhesion is mediated by a heterophilic interaction between neuropilin and protease-sensitive molecules on fibroblasts. The expression of chick neuropilin is restricted to certain neuronal circuits and is dynamically regulated during development, as is the Xenopus homologue. However, their expression patterns differed significantly in the visual systems between the two species: In the chick optic tectum, the localization of neuropilin is confined to layers d and e of SGFS, two of the six layers receiving the retinal input; the chick optic nerve fibers do not express neuropilin; in the chick retina, amacrine cells transiently express neuropilin. Cultured neurons of the dorsal root ganglia express chick neuropilin on their neurites including growth cones. These results suggests that neuropilin functions as a cell adhesion molecule during the formation of certain neuronal circuits in vivo.

3T3 Cells↗
PubMed1995

Quinidine enhances intracellular Ca2+ accumulation during rapid stimulation.

1. The quinidine-induced modification of intracellular Ca2+ concentration ([Ca2+]i) was studied in guinea-pig myocardium using fura-2. Quinidine reduced the systolic fluorescence signal level for [Ca2+]i and enhanced the end-diastolic signal level during a stimulation train. 2. The diastolic decay of [Ca2+]i fitted 2 exponential curves. Quinidine distorted the stimulation frequency-dependent acceleration of rapid [Ca2+]i decay, and prolonged the mean time constant of rapid decay after 2 Hz stimulation, from 154.4 to 205.3 msec (20 microM), and to 259.7 msec (60 microM quinidine). The time constant of slow recovery from [Ca2+]i accumulation after the stimulation train was not affected by stimulation frequency, or by quinidine, or caffeine. 3. These results suggest that quinidine modulates [Ca2+]i via a balance between the slowing of rapid [Ca2+]i decay and the reduction of the systolic [Ca2+]i. This effect may contribute to the anti-arrhythmic and pro-arrhythmic effects exerted by quinidine in some conditions.

Animals↗
PubMed1995

Polarized Raman spectra of oriented fibers of A DNA and B DNA: anisotropic and isotropic local Raman tensors of base and backbone vibrations.

Polarized Raman spectra of oriented fibers of calf thymus DNA in the A and B conformations have been obtained by use of a Raman microscope operating in the 180 degrees back-scattering geometry. The following polarized Raman intensities in the spectral interval 200-1800 cm-1 were measured with both 514.5 and 488.0 nm laser excitations: (1) Icc, in which the incident and scattered light are polarized parallel to the DNA helical axis (c axis); (2) Ibb, in which the incident and scattered light are polarized perpendicular to c; and (3) Ibc and Icb, in which the incident and scattered light are polarized in mutually perpendicular directions. High degrees of structural homogeneity and unidirectional orientation were confirmed for both the A and B form fibers, as judged by comparison of the observed Raman markers and intensity anisotropies with measurements reported previously for oligonucleotide single crystals of known three-dimensional structures. The fiber Raman anisotropies have been combined with solution Raman depolarization ratios to evaluate the local tensors corresponding to key conformation-sensitive Raman bands of the DNA bases and sugar-phosphate backbone. The present study yields novel vibrational assignments for both A DNA and BDNA conformers and also confirms many previously proposed Raman vibrational assignments. Among the significant new findings are the demonstration of complex patterns of A form and B form indicator bands in the spectral intervals 750-900 and 1050-1100 cm-1, the identification of highly anisotropic tensors corresponding to vibrations of base, deoxyribose, and phosphate moieties, and the determination of relatively isotropic Raman tensors for the symmetrical stretching mode of phosphodioxy groups in A and B DNA. The present fiber results provide a basis for exploitation of polarized Raman spectroscopy to determine DNA helix orientation as well as to probe specific nucleotide residue orientations in nucleoproteins, viruses, and other complex biological assemblies.

Animals↗
PubMed1995

A patient with an autonomously functioning thyroid nodule with papillary adenocarcinoma associated with Graves' hyperthyroidism.

A 69-year-old man had concomitant findings of an autonomously functioning thyroid papillary adenocarcinoma and Graves' hyperthyroidism. The patient presented with hyperthyroidism and a right lobe thyroid nodule that was shown to be hyperfunctional on I-123 imaging. The TI-201 imaging showed uptake confined almost entirely to the right lobe nodule. Papillary adenocarcinoma in the nodule and diffuse hyperplasia surrounding the nodule along with a slightly enlarged left lobe were found at surgery.

Adenocarcinoma, Papillary↗
PubMed1995

Two cases of duodenal gangliocytic paraganglioma: immunocytochemical characteristics.

Two cases of duodenal gangliocytic paraganglioma were studied by means of immunocytochemical methods using 41 kinds of antibodies. The tumors consisted of three histological types; carcinoid, ganglioneuroma and paraganglioma. Tumors of both cases exhibited immunoreactivity to at least one or as many as three of the following: calcitonin, calcitonin-gene related peptide, endocrine granule constituent, Leu7, neuropeptide Y and basic fibroblast growth factor. In addition, these tumors were also immunopositive for neuron specific enolase, S-100 protein, neurofilament protein, pancreatic polypeptide, chromogranin A, somatostatin, leuenkephalin, substance P and vasoactive intestinal peptide, as has been described in previous reports. In one case, tumor cells were immunopositive for adrenocorticotropin, bombesin, gastrin releasing peptide, myelin basic protein, neuroendocrine marker and tyrosine hydroxylase. Moreover, paraganglioma cells of tumors showed both argyrophilia and argentaffinity. These results suggest that duodenal gangliocytic paraganglioma may originate from embryonic neuroinsular complex.

Duodenal Neoplasms↗
PubMed1994

Increase in cytosolic free Ca2+ in corticotropin-stimulated white adipocytes.

The mechanism of the adrenal corticotropin hormone (ACTH)-stimulated increase in cytosolic free Ca2+ concentration ([Ca2+]i) was investigated in rat white adipocytes. ACTH at concentrations > 10 mU/ml caused a rapid and transient increase in [Ca2+]i followed by a small but sustained elevation of [Ca2+]i. A similar phenomenon was also induced by alpha-adrenergic or synthetic ACTH stimulation. The effect of norepinephrine (NE) plus ACTH on [Ca2+]i was nearly additive. Pertussis toxin completely blocked the ability of ACTH or NE to increase [Ca2+]i. NE but not ACTH caused a significant increase in inositol 1,4,5-trisphosphate levels. ACTH caused a rapid and transient accumulation of [3H]arachidonic acid (AA) and a marked loss of [3H]AA from phosphatidylinositol (PI) and phosphatidylcholine (PC) 10 s after stimulation. Neither a lipoxygenase inhibitor nor a dual inhibitor of cyclooxygenase and lipoxygenase blocked the increases in [Ca2+]i and the accumulation of [3H]AA in response to ACTH. On the other hand, either pertussis toxin or phospholipase A2 inhibitor drastically blocked both parameters in response to ACTH. These results indicate that ACTH stimulates AA release from PC and PI via the activation of phospholipase A2 coupled with pertussis toxin-sensitive GTP-binding protein(s), which leads to an increase in [Ca2+]i in rat white adipocytes.

Acetophenones↗
PubMed1994

Changes in mouse hippocampal EEG characteristics after oral administration of Ro 41-3696, nitrazepam, or zopiclone alone and in combination with ethanol.

Ro 41-3696, a benzoquinolizinone derivative, is a partial agonist to the benzodiazepine (BDZ) receptor and is expected to be a nonsedative hypnotic. The present comparative study was performed to examine the effects of the oral administration of Ro 41-3696, nitrazepam or zopiclone alone and in combination with a 'social' dose of ethanol on mouse hippocampal EEG. Ro 41-3696 (1-10 mg/kg), nitrazepam (0.1 and 1 mg/kg), and zopiclone (1 and 10 mg/kg) each alone caused an increase in the drowsy EEG pattern associated with a decrease in the duration of hippocampal rhythmic slow-wave activity (RSA). On the other hand, nitrazepam markedly lowered, while Ro 41-3696 and zopiclone slightly lowered the RSA frequency during waking mobility. In combination with a noneffective oral dose (1 g/kg) of ethanol, the reductions in both total duration and peak frequency of RSA caused by nitrazepam, unlike those by Ro 41-3696 and zopiclone, were significantly potentiated. In addition, only nitrazepam produced motor impairment. These results suggest that Ro 41-3696 acts more selectively than nitrazepam to promote the drowsy EEG pattern, and the partial agonistic properties may minimize the residual effects during waking mobility similar to the short-acting agent zopiclone.

Animals↗