Separable regulatory elements from pro-alpha 2 (XI) collagen gene drive distinct patterns of cartilage-specific expression in transgenic mice.
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Animals↗
Biomedical subjects
T Ochi
Publications and source records attributed to T Ochi.
Transient introduction of a foreign gene into healing rat patellar ligament.
We investigated the in vivo introduction of a reporter gene into healing rat patellar ligaments using the hemagglutinating virus of Japan (HVJ)-liposome-mediated gene transfer method. The mid-portion of the medial half of the patellar ligament was cut transversely with a scalpel in 14-wk-old male Wistar rats. A HVJ-liposome suspension containing beta-galactosidase (beta-gal) cDNA was injected directly into the injured site and pooled in the fascial pocket covering the injured site 3 d postoperatively. Thereafter, beta-gal-labeled cells were observed in the wound site accounting for 3% of the wound cells on the first day, 2% on the third, 7% on the seventh, 6% on the 14th, 2% on the 28th, and 0.2% on the 56th day after injection. The beta-gal-labeled cells were initially localized in and adjacent to the wound site, but they were observed spreading into the ligament substance away from the wound on the seventh day after injection. On day 28, beta-gal-labeled cells were observed throughout the length of the ligament substance. With double-labeling for marker antigens for monocyte/macrophage (ED-1) and for collagen I aminopropeptide (pN collagen I), it was revealed that fibroblastic (pN collagen I-positive) cells accounted for 63% and monocyte/macrophage lineage cells for 32% of the beta-gal-labeled cells in the day 7 wound. On day 28, they formed 58 and 35% of the beta-gal-labeled cells in the wound, respectively. Thus, we succeeded in introducing the beta-gal gene into healing rat patellar ligament. Moreover, labeling of the transfected cells made it possible to identify a biological event, namely that the cells in and around the wound site infiltrate into the uninjured ligament substance and come to populate the whole length of the ligament substance as repair progresses. These results suggest that ligament healing may involve not only the repair of the wound site itself but also extensive cellular infiltration of ligament substance adjacent to the wound.
Animals↗
Elevated levels of the soluble form of bone marrow stromal cell antigen 1 in the sera of patients with severe rheumatoid arthritis.
OBJECTIVE: Bone marrow stromal cell antigen 1 (BST-1) is a novel glycosyl phosphatidylinositol-anchored ectoenzyme, which is overexpressed on bone marrow stromal and synovial cell lines derived from patients with rheumatoid arthritis (RA). To investigate the pathophysiologic roles of BST-1 in RA, we established an enzyme-linked immunosorbent assay (ELISA) system to detect the soluble form of BST-1 (sBST-1) and examined levels of sBST-1 in the sera of RA patients. METHODS: Concentrations of sBST-1 in sera from healthy donors and from patients with RA, osteoarthritis, Sjögren's syndrome, and systemic lupus erythematosus were measured with the ELISA. RESULTS: In 7% of the RA patient samples (10 of 143), concentrations of serum sBST-1 were higher (approximately 30-50-fold) than in non-RA samples. Serum sBST-1 concentrations showed no correlation with age, C-reactive protein level, or rheumatoid factor level. All RA patients with high concentrations of serum sBST-1 had severe disease with involvement of several large joints. CONCLUSION: We believe the measurement of serum sBST-1 may have prognostic value, but further analysis is necessary to clarify the clinical significance of elevated sBST-1 in RA.
ADP-ribosyl Cyclase↗
Accelerated generation of CD14+ monocyte-lineage cells from the bone marrow of rheumatoid arthritis patients.
OBJECTIVE: To examine the capacity of bone marrow progenitor cells to generate CD14+ cells, in order to assess the role of bone marrow in the pathogenesis of rheumatoid arthritis (RA). METHODS: CD14- cells purified from bone marrow specimens of 11 patients with active RA and 8 control patients (osteoarthritis or trauma) were cultured in the presence or absence of granulocyte-macrophage colony-stimulating factor (GM-CSF; 100 pg/ml). After incubation for various lengths of time, the cells were analyzed by flow cytometry for expression of CD14 and HLA-DR. RESULTS: The spontaneous generation of CD14+ cells from bone marrow CD14- progenitor cells was accelerated in RA patients compared with control patients. Moreover, the expression of HLA-DR on the bone marrow-derived CD14+ cells was also accelerated in RA patients compared with controls. GM-CSF significantly enhanced the generation of CD14+ cells, as well as the expression of HLA-DR, on CD14+ cells of control patients, but not those of RA patients. GM-CSF levels in the culture supernatants of bone marrow CD14- cells were not significantly different between RA patients and control patients (undetectable in most cases). CONCLUSION: These observations strongly support the hypothesis that the accelerated generation of CD14+ cells from bone marrow progenitor cells and the accelerated maturation of such CD14+ cells into HLA-DR+ cells play an important role in the pathogenesis of RA. Moreover, the data suggest a functional alteration of RA bone marrow CD14- cells in their responsiveness to GM-CSF.
Adult↗
Shoulder destruction in rheumatoid arthritis. Classification and prognostic signs in 83 patients followed 5-23 years.
We studied the natural course and the possibility of making prognoses about shoulder joint destructions in 83 patients with rheumatoid arthritis (RA) (166 shoulder joints). For this purpose, we used radiographic patterns and 2 indices (upward migration and medial displacement). The patterns of joint destruction were classified into 5 groups: 1) non-progressive type (n 74) with normal radiographs, only osteopenia or small erosions even after 15-20 years of RA; 2) erosive type (n 22) showing marginal erosions but no collapse; 3) collapse type (n 34) showing subchondral cysts, followed by collapse; 4) arthrosis-like type (n 12) showing arthrotic features; 5) mutilating type (n 14) showing mutilating bone destructions. From the radiographic findings and the 2 indices determined at 5-10 years, we could predict the prognosis of shoulder joint destruction after 15-20 years of RA. Our findings may be of value for selecting treatment, including surgery, for the rheumatoid shoulder.
Adult↗
MRI of early osteonecrosis of the femoral head after transcervical fracture.
We have carried out a prospective study of 17 patients (14 women, 3 men) of mean age 48 years (21 to 76) with transcervical fractures of the femur using MRI to detect early evidence of avascular necrosis of the head. Two fractures were Garden stage I, 12 stage II, and three stage III. We performed internal fixation under radiological control at a mean of five days (2 to 15) after injury using a titanium cannulated cancellous screw or a titanium compression hip screw. MRI was performed at one, six and 12 months and then yearly after operation. T1- and T2-weighted images were obtained by a spin-echo technique. The duration of follow-up of patients who did not subsequently require replacement of the head of the femur was from 2 to 5 years (mean 3.2). One month after operation eight of the 17 hips showed a band of low signal intensity on T1-weighted images and high signal intensity on T2-weighted images indicating lesions in the femoral head away from the fracture line. These were of three types: type I was a small infarct at the superolateral region of the femoral head and was seen in three hips; type II was a shallow lesion from the superolateral region to the fovea of the femoral head (three hips); and type III was a large lesion occupying most of the femoral head (two hips). No further changes were seen in the MRI after six months from operation. Collapse of the femoral head did not occur in the three hips with type-I lesions, but two of the three type-II hips and both type-III hips subsequently collapsed. At the final follow-up the three hips with a type-I lesion and one with a type-II were still asymptomatic but radiography showed sclerosis in the femoral head corresponding to the MRI lesions. The nine hips which showed no changes on MRI at one month had no abnormal findings on physical examination, radiography or MRI at final follow-up.
Adult↗
Moloney murine leukemia virus infection accelerates lymphomagenesis in E mu-bcl-2 transgenic mice.
E mu-bcl-2 transgenic mice bearing the bcl-2 proto-oncogene linked to the immunoglobulin enhancer (E mu) sporadically develop B or T cell lymphomas after a long latent period. To identify genes that play important roles in development of lymphoid malignancies, proviral insertional mutagenesis with Moloney murine leukemia virus (MMuLV) was carried out in two lines of transgenic mice expressing the bcl-2 gene primarily in B or T cells. MMuLV infection of non-transgenic mice induced primarily mature T cell lymphomas. By contrast, infection of newborn E mu-blc-2 mice with the virus accelerated lymphomagenesis, and nearly all of the mice eventually succumbed to clonal pre-B, B, or mainly immature T cell lymphoma, indicating the active contribution of the bcl-2 gene in lymphomagenesis. Southern blot analysis of tumor DNA from MMuLV-infected transgenic mice revealed a proviral insertion at the c-myc gene in 26% (9/35) of tumors, at the pim-1 gene in 6% (2/35) and at the pim-2 (recently renamed tic-1) gene in 23% (8/35). Some tumors carried two activated oncogenes. No insertion was detected at the bmi-1 gene. These data suggest the usefulness of this transgenic system for analysis of lymphomagenesis involving the activated bcl-2 gene.
Aging↗
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↗
Serum phospholipase A2 activity and immunoreactive group II phospholipase A2 in rheumatoid arthritis.
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Adult↗
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↗
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↗
[A case of primary rhabdomyosarcoma of liver at autopsy--literature review of 7 cases reported in Japan].
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Aged↗
[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↗