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Biomedical subjects

T Ochi

Publications and source records attributed to T Ochi.

At least 217 records · Page 12Linked to original sources

Natural course of cervical spine lesions in rheumatoid arthritis.

STUDY DESIGN: This study analyzed the natural course of cervical spine involvement in rheumatoid arthritis by serial radiographs. OBJECTIVES: The purpose was to determine the pattern of progression of cervical spine lesions in rheumatoid arthritis and predictors for the extent of progression. SUMMARY OF BACKGROUND DATA: Subluxation frequently occurs as a result of rheumatoid involvement of the cervical spine. It may be severe in patients with mutilans deformities in the hands and feet. The extent of progression in a given patient is still unpredictable. METHODS: Serial cervical radiographs in 49 patients with rheumatoid arthritis were analyzed. The extent of progression was evaluated by rheumatoid arthritis subset defined previously, which reflected the final extent of joint erosion in this systemic disease and could be roughly classified during early stages of the disease. RESULTS: In the upper cervical spine, reducible anterior atlantoaxial subluxation occurred first. Vertical subluxation of the axis appeared next. Irreducible change of preceding anterior atlantoaxial subluxation was a sign of the start of vertical subluxation. In subaxial lesion, subluxation occurred less frequently (22.4%) than upper cervical lesion (77.6%). The extent of progression was different with the rheumatoid arthritis subset. In the upper cervical spine, none of the subset with least erosive disease developed vertical subluxation, whereas 52% of the subset with more erosive disease and 88% of the subset with mutilating disease advanced to vertical subluxation. The extent of progression was well correlated with the number of joints with erosion. Subaxial subluxation was often seen and became irreducible in mutilating disease and more erosive disease, but not in least erosive disease. CONCLUSIONS: A progressive pattern of the upper cervical subluxations was clarified. That is, upper cervical lesions progressed from reducible anterior atlantoaxial subluxation to irreducible anterior atlantoaxial subluxation with vertical subluxation. This extent of progression was different with the rheumatoid arthritis subset, which was also related to the development of subaxial subluxation. The most aggressive arthritis classification, a subset with mutilating disease, had the more severe subluxation in both upper and subaxial cervical spine.

Adolescent↗

Molecular cloning and chromosomal mapping of a bone marrow stromal cell surface gene, BST2, that may be involved in pre-B-cell growth.

Bone marrow stromal cells regulate B-cell growth and development through their surface molecules and cytokines. In this study, we generated a mAb, RS38, that recognized a novel human membrane protein, BST-2, expressed on bone marrow stromal cell lines and synovial cell lines. We cloned a cDNA encoding BST-2 from a rheumatoid arthritis-derived synovial cell line. BST-2 is a 30- to 36-kDa type II transmembrane protein, consisting of 180 amino acids. The BST-2 gene (HGMW-approved symbol BST2) is located on chromosome 19p13.2. BST-2 is expressed not only on certain bone marrow stromal cell lines but also on various normal tissues, although its expression pattern is different from that of another bone marrow stromal cell surface molecule, BST-1. BST-2 surface expression on fibroblast cell lines facilitated the stromal cell-dependent growth of a murine bone marrow-derived pre-B-cell line, DW34. The results suggest that BST-2 may be involved in pre-B-cell growth.

Amino Acid Sequence↗

Selective induction of IgM rheumatoid factors by CD14+ monocyte-lineage cells generated from bone marrow of patients with rheumatoid arthritis.

OBJECTIVE: To determine the capacity of CD14+ monocyte-lineage cells induced from bone marrow of rheumatoid arthritis (RA) patients to stimulate the production of IgM rheumatoid factor (IgM-RF), in order to explore the functional abnormalities of CD14+ cells and gain insight into the mechanism of selective synthesis of IgM-RF in RA. METHODS: CD14+ cells were induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation of CD14- cells purified from bone marrow cells obtained from 6 RA patients and 6 osteoarthritis (OA) patients. The production of IgM and IgM-RF was induced by stimulating B cells from normal healthy individuals with immobilized anti-CD3-activated autologous CD4+ T cells. The effects of CD14+ cells on the proportion of IgM-RF to total IgM produced by the normal B cells were assessed. RESULTS: CD14+ cells induced by GM-CSF stimulation of bone marrow CD14- cells from the 6 RA patients significantly enhanced the proportion of IgM-RF to total IgM produced by anti-CD3-activated CD4+ T cell-stimulated normal B cells (P < 0.05), whereas GM-CSF-induced CD14+ cells from the bone marrow of the 6 OA patients did not significantly affect IgM-RF production. CD14+ cells induced by GM-CSF obtained from different sites in the same RA patient on different occasions consistently enhanced the proportion of IgM-RF to IgM produced by B cells from different normal subjects. CONCLUSION: These results indicate that abnormal CD14+ monocytes stimulate RF-producing B cells to be ready to be activated by the signals delivered through noncognate T-B interactions with anti-CD3-activated T helper cells. Moreover, the data suggest that the accelerated generation of such functionally abnormal CD14+ cells from bone marrow precursors might play an important role in the pathogenesis of RA.

Aged↗

The immune reaction to heterologous serum causes osteonecrosis in rabbits.

Osteonecrosis (ON) was produced experimentally in rabbits by intravenous injection of horse serum. Eighty adult rabbits were used: 16 were injected twice with isotonic saline (Group A), 24 were injected once with saline and once with horse serum (Group B), and 40 were injected twice with horse serum (Group C). Both femurs of each rabbit were obtained from 2 h to 7 weeks after the final injection an were subjected to histological examination. No pathological changes were seen in Groups A and B. In Group C, 5 of 15 rabbits (33%) showed ON (necrosis of trabecula and bone marrow) in the femoral metaphysis. In Group C, the early major pathological findings in bone marrow are extravasation of erythrocytes in sinusoidal spaces and microthrombi in small arteries and arterioles near the lesion of extravasation. Immune complexes were demonstrated in the kidney within 24 h of the final injection of horse serum. The present study suggests that immunological reaction associated with serum sickness may play an important role in inducible ON and this model will contribute toward clarifying the pathogenesis of ON.

Animals↗

Hydrogen peroxide increases the activity of gamma-glutamylcysteine synthetase in cultured Chinese hamster V79 cells.

Hydrogen peroxide (H2O2) caused a rapid and a concentration-dependent increase in the activity of gamma-glutamylcysteine synthetase (gamma-GCS) in cultured Chinese hamster V79 cells. The increase in the activity was transient and declined rapidly during post-treatment incubation. Inhibition of protein synthesis by cycloheximide, chelation of divalent iron by o-phenanthroline, and scavenging of free radicals by butyl-4-hydroxyanisole failed to suppress the increase in activity of gamma-GCS caused by H2O2. However, catalase completely inhibited the increase in the activity of the enzyme. H2O2 did not change the level of total glutathione (GSH + GSSG) but it oxidized GSH. The increase in levels of GSSG caused by H2O2 was enhanced by o-phenanthroline. These results suggest that the increase in activity of gamma-GCS caused by H2O2 is not an inducible phenomenon, nor it is attributable to the action of free radicals generated by an iron-catalyzed Fenton reaction. Furthermore, the changes in levels of GSH and GSSG caused by H2O2 appear not to be responsible for the increase in activity of gamma-GCS caused by the hydroperoxide. However, chemical reduction of the enzyme, the activity of which had been increased by H2O2, resulted in a decrease in tha activity, suggesting the involvement of oxidation of the enzyme in the increased activity of gamma-GCS caused by H2O2. The results also suggest that the activity of gamma-GCS in cultured V79 cells can be regulated by the cellular oxidation-reduction state.

Animals↗

The biological activity of hydrogen peroxide. VI. Mechanism of the enhancing effects of L-histidine: the role of the formation of a histidine-peroxide adduct and membrane transport.

Further details of the mechanism of the enhancing effects of L-histidine (L-His) on the clastogenic activities of hydrogen peroxide (H2O2) were investigated. The L-His-H2O2 adduct was prepared and its physicochemical properties and biological activities were compared with those of a mixture of L-His plus H2O2 and of H2O2 alone. When the stabilities of the three test samples against glucose were determined in terms of residual H2O2 content in solutions of various pH values over the course of 11 days, the adduct was found to be more stable than H2O2 alone and very similar in terms of stability to the mixture. The almost equivalent stability of the adduct and the mixture suggested formation of the adduct in the mixture even though the interaction between L-His and H2O2 in solution seems, from 13C-NMR analysis, to be rather weak. In cell-free DNA after lysis of cell membranes, the induction of single-strand breaks (SSB) by the adduct and by the mixture was less effective than by H2O2 alone. These results contrast with previous results obtained in intact cells (Oya et al., 1992) and demonstrate the indispensability of the cell membrane for the enhancing effects of L-His. In the presence of inhibitors of the active transport of L-His, namely, 10 different neutral amino acids, effective suppression of the clastogenic activity of the adduct and of the mixture was observed, whereas four acidic and basic amino acids had no effect. Thus, the participation of active transport in the enhancing effects of L-His was apparent. The formation of the adduct of L-His with H2O2 brings about the stabilization or reduces the reactivity of H2O2 and, as a result, the induction of SSB is prevented to some extent in cell-free DNA systems. By contrast, in a cellular system, the accumulation of the adduct in cells by active transport is potentiated by the enhancing effect of L-His, although the mediation of some factors that can generate hydroxyl radicals (*OH) from the adduct in cells must be postulated.

Biological Transport↗

Hemangioma of the esophagus: endosonographic imaging and endoscopic resection.

A 49-year-old Japanese man was seen to have an esophageal tumor on a routine barium swallow examination. Endoscopy revealed a sessile polyp covered by an almost normal esophageal mucosa, and the bioptic histology was non-diagnostic. Endoscopic ultrasonography showed a hypoechoic tumor with a diameter of 12 mm, confined to the submucosal layer, with the underlying muscularis propria layer being intact. On the basis of this finding, endoscopic resection was chosen and the tumor was resected using a two-channel endoscope, with prior hypertonic saline and epinephrine injection. The pathologic diagnosis was a cavernous hemangioma of the esophagus.

Esophageal Neoplasms↗

A human monoclonal antibody to a human self-antigen, CD2 derived from human peripheral blood lymphocytes engrafted in SCID mice.

To establish human hybridoma lines, production of human immunoglobulin (Ig) and behavior of the implanted human peripheral blood lymphocytes (PBL) were characterized in severe combined immunodeficiency (SCID) mice. Human PBL from healthy donors were injected into the peritoneal cavity of SCID mice, and they were immunized with self-antigen, CD2. CD45+ cells (human PBL) migrated to lymphoid tissues in the mice as early as 4 days, accounting for more than half the lymph node cells and thymocytes. The number of cells releasing human IgG specific to the antigen increased 3.5 weeks after immunization without the usual constraint that production of the IgG, an autoantibody, is prohibited by immunological tolerance in humans. Therefore, we established several human hybridomas secreting human IgG to CD2, since splenocytes and lymph node cells from the implanted SCID mice at 3.5 weeks were fused with a human B lymphoblastoid cell line. A human anti-CD2 monoclonal antibody (MAb) was confirmed to bind to natural CD2 on human T cells by flow cytometric analysis. The epitope for the MAb was identical with a portion that the ligand LFA-3 binded, so that the MAb might reduce the inflammatory reaction caused by preventing activation of human T cells. Here, we report that the human immune system could be reconstituted in SCID mice to develop human hybridomas producing human MAb to a human self-antigen.

Animals↗

[Stereoselective synthesis and pharmacological properties of metabolites of new antiinflammatory agent. 4'-Acetyl-2'-(2,4-difluorophenoxy)methanesulfonanilide (FK3311)].

Asymmetric reduction of acetophenone (FK3311: 1) and ethyl phenylglyoxylate (7) with various chiral reducing agents was investigated in an attempt to synthesize both optical isomers of the two metabolites (2 and 5) of 1. The treatment of 1 with 3,3-diphenyl-1-methyltetrahydro-1H,3H-pyrrolo[1,2-c]-[1,3,2]- oxazaborolidine-borane complex (reductants B, C) gave chiral alcohol 2 in a high optical purity. On the other hand, reduction of 7 by B-chlorodiisopinocamphenylborane (reductants E, F) gave the best result among the tested reagents. Each isomer of 2 and 5 was examined for in vitro activity to inhibit zymosan-induced prostaglandine E2 production, adjuvant-induced arthritis for antiinflammatory activity, and acetic acid-induced writhing for analgesic activity in comparison with the racemic mixture.

Analgesics↗

[Pulmonary complications in patients with rheumatoid arthritis].

Pulmonary manifestations of rheumatoid arthritis were studied in 26 patients. Pulmonary complications could be divided into four subgroups: Interstitial pneumonia/Pulmonary fibrosis (n = 18), Bronchiolitis Obliterans Organizing Pneumonia (n = 4), Bronchiolitis Obliterans (n = 2), and Pleuritis/Pericarditis (n = 1). Analysis of cells in broncho-alveolar lavage fluid (BALF) revealed abnormally high percentages of lymphocytes in one-half of the patients and abnormally high percentages of neutrophils in one-third of the patients. The percent of BALF cells that were neutrophils was higher with higher chest radiograph grades. Analysis of soluble constituents of BALF indicated local production of IgG in two cases, but IgM-rheumatic factor was not detected. In 18 of 26 patients corticosteroid or immunosuppressive drugs were needed, and most of the patients responded to the therapy and had good outcomes. The conditions of 6 patients with interstitial pneumonia/pulmonary fibrosis deteriorated and 4 patients died of progressive respiratory failure. The subclassification of rheumatoid lung was useful for predicting its outcome.

Aged↗

BST-1, a surface molecule of bone marrow stromal cell lines that facilitates pre-B-cell growth.

Bone marrow stromal cells are essential for B-lymphocyte development. However, how stromal cells regulate B lymphopoiesis is not clear. In this paper, we report the molecular cloning of a stromal cell line-derived glycosyl-phosphatidylinositol-anchored molecule, BST-1, that facilitates pre-B-cell growth. The deduced amino acid sequence of BST-1 exhibited 33% identity with CD38. BST-1 was expressed in a wide range of tissues and in umbilical vein endothelial cells, whereas it was scarcely expressed in a variety of hematopoietic cell lines. The gene for BST-1 was assigned to chromosome 14q32.3, where immunoglobulin heavy-chain genes are clustered. BST-1 expression was enhanced in rheumatoid arthritis patient-derived bone marrow stromal cell lines that were previously shown to have an enhanced ability to support the growth of a pre-B-cell line as compared with stromal cell lines derived from healthy donors.

ADP-ribosyl Cyclase↗

Glutathione plays different roles in the induction of the cytotoxic effects of inorganic and organic arsenic compounds in cultured BALB/c 3T3 cells.

The cytotoxicity of arsenic compounds towards BALB/c 3T3 cells in culture was investigated, together with the role of glutathione (GSH) in the induction of the cytotoxic effects. The rank order of cytotoxicity was as follows: arsenite (As3+) > arsenate (As5+) > dimethylarsinic acid (DMAA) > methylarsonic acid (MAA) > trimethylarsine oxide (TMAO). Arsenobetaine, arsenocholine and the tetramethylarsonium ion were less toxic. Depletion of GSH enhanced the cytotoxic effects of As3+, As5+, MAA and TMAO, while the cytotoxicity of DMAA was markedly reduced by depletion of GSH. These results suggest that GSH plays a role in protecting the cells against the toxic effects of As3+, As5+, MAA and TMAO while it is involved in the induction of the cytotoxic effects of DMAA.

3T3 Cells↗

Effects of long-term treatment with sustained-release nicardipine on left ventricular hypertrophy and function in patients with essential hypertension.

The effects of long-term treatment with sustained-release nicardipine (nicardipine SR) on left ventricular hypertrophy and function were studied. Ten uncomplicated essential hypertensive patients with left ventricular hypertrophy, aged 61 +/- 7.6 years old, were treated with nicardipine SR alone for an average of 20 months (range: 12-26 months). All patients underwent echocardiography for assessment of left ventricular diameters and function before and after the treatment. At the end of the treatment, systolic and diastolic blood pressures significantly decreased from 176.0 +/- 13.9 to 140.0 +/- 14.3 mm Hg and from 97.0 +/- 5.3 to 77.4 +/- 7.2 mm Hg, respectively (each P < 0.01), while heart rate did not change (73.8 +/- 14.6 vs. 69.9 +/- 13.5 beats/min). The left ventricular mass index significantly decreased from 132.1 +/- 14.4 to 114.4 +/- 15.7 g/m2 (P < 0.01) due to significant reductions in both interventricular septal thickness (P < 0.01) and left ventricular posterior wall thickness (P < 0.05). The ejection fraction (EF), fractional shortening (FS), peak shortening rate (PSR), and peak lengthening rate (PLR) were also improved significantly by the treatment (EF and FS, P < 0.05; PSR and PLR, P < 0.01). Significant inverse relationships existed between end-systolic wall stress and peak shortening or lengthening rate before the treatment (r = 0.80, P < 0.05; r = 0.86, P < 0.05, respectively). These relationships were unchanged after the treatment. Nicardipine SR reduced left ventricular hypertrophy and improved both left ventricular systolic and diastolic functions without causing any consistent augmentation of intrinsic left ventricular function in essential hypertensive patients with left ventricular hypertrophy.

Aged↗

Mechanism for the decrease in the accumulation of cadmium (Cd) in Cd-resistant Chinese hamster V79 cells.

The mechanism for the decrease in the accumulation of cadmium (Cd) in Cd-resistant Chinese hamster V79 (Cdr) cells in culture was investigated in a comparison with Cd-sensitive (Cds) cells. Both Cdr and Cds cells took up Cd in a time-dependent manner but the rate of uptake of Cd by Cdr cells was about 15% of that by Cds cells. Kinetic studies of the uptake of Cd showed that the Vmax values for Cdr and Cds cells were 0.31 and 0.46 pmol Cd/h per mg protein, respectively. The Km values were 31.95 microM for Cdr cells and 3.15 microM for Cds cells. Mersalyl acid, a sulfhydryl (SH) blocker to which cells are impermeable, inhibited the uptake of Cd by Cds cells at subtoxic concentrations while Cdr cells were insensitive to inhibition by mersalyl acid, suggesting that SH groups in the plasma membrane play a role in the uptake of Cd. Uptake of Cd by Cds cells was dependent on the pH of the incubation medium and the rate of uptake was very high at pH 7.4 and pH 8.0 relative to the rates at pH 6.0 and pH 6.8. By contrast, the uptake of Cd by Cdr cells was lower at all pH values than that by Cds cells. The decrease in the rate of uptake of Cd by Cdr cells could not be ascribed to an increase in the efflux of Cd. A Cd-blotting technique was used to detect plasma membrane proteins with high affinity for Cd. Two major differences in terms of Cd-binding proteins (Cd-BPs) were observed between Cdr and Cds cells. A 110-kDa Cd-BP, detected in Cds cells, was found at a reduced level in Cdr cells, while an 82-kDa Cd-BP, which was not observed in Cds cells, was detected in Cdr cells.

Animals↗

Remarkable elevation of interleukin 6 and interleukin 8 levels in the bone marrow serum of patients with rheumatoid arthritis.

OBJECTIVE: Characteristic cellular changes have previously been reported in the bone marrow of patients with rheumatoid arthritis (RA). We investigated the levels of various cytokines in RA bone marrow. METHODS: We studied 25 patients with RA (22 women and 3 men) and 10 trauma patients (7 women and 3 men) as non-RA controls. Twelve kinds of cytokines [interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-6, IL-7, IL-8, granulocyte colony stimulating factor, granulocyte/macrophage colony stimulating factor, tumor necrosis factor (TNF)-alpha, and TNF-beta] were assayed by ELISA in iliac bone marrow serum (BMS), tibial BMS, and peripheral blood serum. RESULTS: Markedly elevated levels of IL-6 and IL-8 were detected in iliac BMS, and much lower levels were found in tibial bone marrow and peripheral blood serum. The levels of IL-6 and IL-8 in iliac BMS showed a close relationship to the extent of synovial proliferation. CONCLUSION: Iliac bone marrow may be an important site for the production or accumulation of IL-6 and IL-8 in RA, and these cytokines may influence synovial proliferation in patients with polyarthritis.

Adult↗