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Biomedical subjects

Y Ichikawa

Publications and source records attributed to Y Ichikawa.

971 records · Page 54Linked to original sources

Lupus cystitis and performation of the small bowel in a patient with systemic lupus erythematosus and overlapping syndrome.

We describe a patient with systemic lupus erythematosus (SLE) and overlapping syndrome who had repeated gastrointestinal (GI) symptoms such as nausea, vomiting and malabsorption. With a subacute process, she developed paralytic ileus and contracted bladder, and died of perforation of the ileum. When 13 reported cases with lupus cystitis were reviewed, an extremely strong correlation between GI and urinary tract symptoms was observed, indicating the presence of a unique subgroup of SLE.

Adult↗

Recurrent lupus pneumonitis with pulmonary hemorrhage in systemic lupus erythematosus associated with chronic thyroiditis and antithyroid hormone autoantibodies.

We describe a SLE patient with repeated lupus pneumonitis and pulmonary hemorrhage. The hemorrhagic episodes were considered to be related to thrombocytopenia and lupus pneumonitis, which have responded well to treatment with moderate doses of steroids and immunosuppressant. She was also found to be suffering from chronic thyroiditis (hypothyroidism) and was positive for anti-thyroid hormone antibodies, which have not been reported before in the SLE patients with thyroid diseases.

Adult↗

Lymphocyte subsets of the peripheral blood in Sjögren's syndrome and rheumatoid arthritis.

Lymphocyte subsets were determined in the peripheral blood from twenty-three patients with primary Sjögren's syndrome (SS) and sixteen patients with clinically active rheumatoid arthritis (RA) by two-color flowcytometry using various monoclonal antibodies. In both diseases, T-cells (CD3+), suppressor/cytotoxic cells (CD8+) and their cytotoxic subset (CD8+CD11-) were decreased, as compared with thirty-one healthy controls. B-cells (CD 21+ and CD 3-DR+) and activated T-cells (CD 3+DR+) were increased in SS patients. Helper T-cells (CD 4+Leu8-), suppressor-inducer T-cells (CD4+Leu8+), suppressor T-cells (CD8+Leu 15+) and three natural killer (NK) cell subsets determined by both CD16 and Leu7 antibodies did not differ between controls and SS or RA, although Leu7+NK cells were significantly increased in SS patients. In addition, we found that the treatment with low-dose prednisolone decreased B-cells and suppressor-inducer T cells, and increased suppressor T-cells, cytotoxic T-cells and Leu7+NK cells. The results indicate similar changes in the proportion of lymphocyte subsets and suggest immunologically activated and deficient conditions in both diseases. Immunomodulating effects of the treatment with low-dose prednisolone on some of the lymphocyte subsets in patients with these diseases were also supported by the study.

Adult↗

Familial Sjögren's syndrome in the Japanese: immunogenetic and serological studies.

Serological abnormalities and HLA haplotypes were studied in a Japanese family of two patients with Sjögren's syndrome (SS) associated with other autoimmune diseases. In contrast to the reports in the U.S.A. and Europe, we found a significant excess of HLA-DRw53 antigen in the family members. Two family members, mother and niece of the probands, had suffered from other connective tissue diseases. Although none of the siblings of probands had manifestations of connective tissue diseases, two siblings had several autoantibodies. No consistent segregation, however, was found between the HLA haplotypes and the serological abnormalities in the relatives. Therefore, HLA alone can not explain the familial clustering of autoimmune diseases including SS and of autoantibodies.

Adult↗

T lymphocyte subsets of the infiltrating cells in the salivary gland and kidney of a patient with Sjögren's syndrome associated with interstitial nephritis.

Lymphocyte subsets in the salivary gland and kidney were examined in a 38 years-old female patient with Sjögren's syndrome associated with interstitial nephritis by PAP immunoperoxidase method using monoclonal antibodies. Predominant cells of the infiltrating cells in both tissues were T lymphocytes and most of them were Ia+, OKT4+ cells (activated helper/inducer T lymphocytes). A small number of T lymphocytes were OKT8+ (suppressor/cytotoxic T lymphocytes). Moreover, we found the OKT8+ cells invading the salivary duct epithelial cells. There was no difference in the proportion of lymphocyte subsets of the infiltrating cells between the salivary gland and kidney. A similar pathologic mechanism of tissue damage, therefore, was suggested in both tissues.

Acidosis, Renal Tubular↗

Immunologic safety of ibuprofen in rheumatoid arthritis: preliminary evidence.

Some evidence indicates that ibuprofen and other prostaglandin synthetase inhibitors may have the potential for cellular immune enhancement in addition to their anti-inflammatory activity. If this is true, treatment of rheumatoid arthritis, a disorder of presumed autoimmune pathogenesis, would present a dilemma. These agents are widely used in rheumatoid arthritis for their anti-inflammatory effects. If they are found to enhance cellular immune function, however, the disease might be stimulated over the long term, rather than suppressed. Preliminary evidence from four patients with rheumatoid arthritis show that oral ibuprofen had no significant immunologic effect during sequential "on" and "off" cycles, as assessed by the following measures: delayed hypersensitivity skin testing; lymphocyte transformation to mitogen (phytohemagglutinin) or specific antigen (Candida albicans); T-cell subsets, as determined by monoclonal antibody techniques; or production of the lymphokine, human immune interferon, in response to phytohemagglutinin or to staphylococcal enterotoxin A. Early evidence, therefore, suggests that oral ibuprofen therapy may be 'immunologically safe' in patients with rheumatoid arthritis, but investigations of large series of patients also assessing local immune reaction in diseased joints may be necessary for confirmation.

Acetaminophen↗

Defective expression of OKT4 antigen on the cell surface of helper T lymphocytes in a patient with systemic lupus erythematosus.

OKT-monoclonal antibodies directed to total T-cells (OKT3), inducer/helper (OKT4) or suppressor/cytotoxic (OKT8) T-cells recognize developmental antigens on human T-cells. We report here an 18 year old male patient with systemic lupus erythematosus who had a prominent decrease in the proportion of OKT4-reactive T-cells in his peripheral blood, although the proportion of OKT3- and OKT8-reactive T-cells were essentially normal. His peripheral blood lymphocytes (PBL) responded well to stimulation by phytohemagglutinin-P (PHA) or concanavalin-A (Con A), which are stimulators for OKT4-reactive T-cells or for both subsets. Furthermore, helper T-cell function for B-cell proliferation was demonstrable in the patient's T-cells which lacked both OKT4 and OKT8 antigens. Trypsinization of PBL from healthy individuals abrogated detection of the OKT4 antigen, and a complete recovery of the antigen was observed after 6 days of culture of the treated PBL. The OKT4 antigen, however, could not be expressed on the patient's PBL after this treatment and incubation. In addition, the patient's serum could not block the recovery of OKT4 antigen on trypsinized T-cells from healthy individuals. The decrease in the percentage of OKT4-reactive T-cells was relatively stable in the patient, while his clinical disease activity and medications were variable. Taken together, these results suggest a defective expression of OKT4 antigen on the helper T-cell subset in this patient.

Adolescent↗

Sjögren's syndrome presenting with hypereosinophilia, lymphopenia and circulating immune complexes.

Although mild peripheral eosinophilia is a common finding in Sjögren's syndrome (SS), severe eosinophilia with a clinical picture simulating hypereosinophilic syndrome is extremely rare. We report a 24 year old male with SS presenting with swelling of the parotid glands, redness and irritation of the eyes, polyarthralgias and polyarthritis, weight loss, exertional dyspnea, malaise, erythematous and urticarial skin lesions and enlarged lymph nodes. Laboratory tests showed hypereosinophilia (34%, total 3800/mm3), lymphopenia (2%, total 220/mm3), a positive RA factor (1:2560) and decreased C3 and C4. Biopsy of an enlarged submaxillary gland was consistent with SS. A Schirmer test showed decreased tear production. Salivary glands showed a marked decrease in uptake of radioactive (Tc99) dye. Circulating immune complexes (CIC) were markedly elevated by both C1q binding and Raji cell assays. T-cell subsets showed OKT3 = 63%, OKT4 = 32% and OKT8 = 16%. "Histamine trap" in vivo test for CIC revealed fluorescence in upper dermal blood vessels with IgM, C1q, C3 and fibrin. Biopsies of the liver, bone marrow and skin revealed eosinophilic infiltration. A notable response to therapy with high doses of corticosteroids was seen with recurrence of symptoms and laboratory abnormalities after the therapy was stopped. In conclusion, we present a case of SS which is remarkable for the age and sex of the patient, extreme hypereosinophilia, marked lymphopenia, and CIC.

Adult↗

Proportional and functional studies of the infiltrating lymphocytes in the parotid gland of Sjögren's syndrome associated with rheumatoid arthritis.

Lymphocyte subpopulations and functions were examined in the salivary (parotid) gland lymphocytes (SGL) obtained as a cell suspension from a patient with Sjögren's syndrome associated with rheumatoid arthritis, in comparison with peripheral blood lymphocytes (PBL). Serial studies on the lymphocyte subsets in PBL using monoclonal antibodies to helper or suppressor T cell subsets (OKT4 or OKT8) demonstrated a decreased proportion of the OKT8 subset (OKT4/OKT8 ratio: 7.1-34.0). Major infiltrating cells in the gland were surface immunoglobulin-bearing B cells, and 23-35% of the SGL were T cells by both the E-rosetting method and OKT3-monoclonal antibody reactivity. Moreover, OKT4/OKT8 ratios were definitely lower in the SGL (1.0 and 1.7) than those in the PBL of the patient. Mitogen-induced lymphocyte proliferative responses of the SGL were markedly diminished, although the possible participation of defective macrophages was considered. The autologous mixed lymphocyte reaction was low in both PBL and SGL. PBL of the patient showed normal proliferative responses to mitogens except for PWM stimulation. Suppressor effects of the SGL for the proliferative responses of autologous and allogeneic PBL were demonstrated. Con A-induced suppressor function was inducible in the SGL, whereas that function could not be demonstrated in the patient's PBL.

Adult↗

Abnormal expression of apoptosis-related antigens, Fas and bcl-2, on circulating T-lymphocyte subsets in primary Sjögren's syndrome.

OBJECTIVE: To clarify the pathological role of the apoptosis-related molecules expressed on peripheral blood (PB) lymphocyte subsets in primary Sjögren's syndrome (SS). METHODS: The levels of apoptosis-regulating proteins, Fas and bcl-2, were determined in the PB lymphocyte subsets from 21 patients with SS and 14 healthy controls by 2-color flow cytometry. RESULTS: In the PB from SS patients, lymphocytopenia, especially CD4+ cell-lymphocytopenia, was prominent. As observed in previous studies, the percentages of CD4+ CD45RA+ cells were lower in the SS patients than in the controls, while activated (DR+) cells were increased in CD4+ cells from the patients. Fas+ cells were also increased in the patients' CD4+ cells and CD8+ cells, but not in their B cells or natural killer cells. Furthermore, we observed several positive correlations among the percentages of activated cells (DR+ cells or CD45RA-cells) and Fas+ cells recognized in the CD4+ and/or CD8+ cells from the patients. On the other hand, intra-cellular bcl-2 proteins measured as mean fluorescence intensity were significantly diminished in the CD4+ cells, CD8+ cells, CD19+ cells, CD45RO+ cells and Fas+ cells from 14 SS patients compared with 12 healthy controls. In addition, the numbers and/or percentages of CD4+ cells and Fas+ cells positively correlated with their expression of bcl-2 in SS patients. CONCLUSION: The abnormal balance between Fas and bcl-2 expression detected in the PB lymphocyte subsets from SS patients relates, at least partially, to the lymphocytopenia observed in the patients.

Adult↗

A functional neointima with regularly arranged smooth muscle cells in a fabric vascular prosthesis transplanted with autologous venous tissue fragments.

Regular arrangement of smooth muscle cells underneath an endothelial cell layer was observed in the neointima of a fabric vascular prosthesis treated with new technology to accelerate endothelialization, i.e., transplantation of autologous venous tissue fragments in the graft wall. This finding indicated that the neointima has a vital function as the intima of the blood vessel. A canine left jugular vein was minced and stirred into 20 ml of saline containing 1,000 IU heparin. It was injected with pressure into a fabric prosthesis (4 mm inner diameter [ID], 3.5 cm in length, Water porosity: 4,000 ml) to create the tissue fragmented, heparinized graft. The graft was implanted into the same animal from which the jugular vein was taken. Forty tissue fragmented heparinized (TFH) grafts were implanted in both carotid arteries of 20 dogs and explanted from 1 hr to 400 days after implantation. In this study, the neointimae of the grafts implanted for more than 1 month are analyzed, with a focus on the arrangement of smooth muscle cells in the neointima. A circumferential arrangement of smooth muscle cells with a thin layer of longitudinally arranged cells underneath was seen in the neointimae, which resemble the arrangement of smooth muscle cells in the natural arterial wall. Some areas had a thin smooth muscle cell layer in the longitudinal direction just under the endothelial cell layer. At anastomotic sites, they ran in parallel rows in the longitudinal direction. The authors previously clarified that the smooth muscle cells arrange in parallel rows in the direction of strain caused by tensile stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Serum matrix metalloproteinase-3 and fibrin degradation product levels correlate with clinical disease activity in rheumatoid arthritis.

OBJECTIVE: Plasmin and matrix metalloproteinase-3 (MMP-3) have been linked to articular destruction in rheumatoid arthritis (RA). We compared circulating levels of plasmin-mediated fibrin degradation product (FDP D-dimer) and MMP-3 with traditional parameters of disease activity in RA to determine their clinical utility. MATERIALS AND METHODS: Serum levels of MMP-3 and D-dimer were determined by enzyme-linked immunoassays in 60 patients with RA. Twenty healthy females and 21 patients with systemic lupus erythematosus (SLE) served as controls. RESULTS: MMP-3 (436.8 +/- 474.2 ng/ml) and D-dimer levels (351.2 +/- 296.3 ng/ml) were markedly elevated in the sera from RA patients as compared with healthy controls (43.9 +/- 15.2 ng/ml and 63.0 +/- 64.1 ng/ml, p < 0.0001, respectively). Both levels strongly correlated with each other (r = 0.627, p < 0.0001) and were closely associated with various clinical parameters for the disease activity of RA, including the erythrocyte sedimentation rate (ESR) and the Lansbury's activity index (p < 0.0001). MMP-3 levels were more highly correlated with articular parameters such as the swollen and painful joint counts (r = 0.454, p = 0.0002), whereas D-dimer levels correlated well with C-reactive protein (CRP) levels (r = 0.581, p < 0.0001). In SLE patients, MMP-3 (239.1 +/- 199.6 ng/ml, p < 0.0001) and D-dimer levels (86.9 +/- 85.2 ng/ml, p = 0.0278) were also higher than in healthy controls. Both levels correlated with each other (r = 0.612, p = 0.0025), and were associated with ESR and CRP levels, as was observed in RA patients, but not with most of the other clinical indicators for SLE. CONCLUSIONS: Serum levels of MMP-3 and D-dimer are clinically useful indicators for disease activity in RA. Our results further support the hypothesis that MMP-3 and plasmin may interact in the inflammatory synovial tissues, and thus augment the articular destruction seen in RA. In SLE patients, however, MMP-3 producing cells could be different from in RA patients, and further studies will be required to clarify the pathogenetic mechanism underlying the raised serum levels of MMP-3 and/or D-dimer.

Adult↗

Anti-agalactosyl IgG antibodies and isotype profiles of rheumatoid factors in Sjögren's syndrome and rheumatoid arthritis.

OBJECTIVE: Rheumatoid factors (RFs) in sera from rheumatoid arthritis (RA) patients bind better to agalactosyl IgG [gal(-) IgG] than to native IgG. Recently, a novel lectin-enzyme immunoassay (LEIA) which can detect all isotypes of the immunoglobulins was developed in Japan. Since RFs are also detectable in Sjögren's syndrome (SS), we determined anti-gal(-) IgG antibodies and RF isotypes in sera from primary or secondary SS and RA patients to elucidate the clinical significance of these antibody profiles. METHODS: A series of 128 patients with primary SS (35 pts.), RA (57 pts.), or secondary SS [n = 36 pts., the SS being associated with RA (RA-SS) in 12 pts., systemic lupus erythematosus (SLE-SS) in 17 pts., and mixed connective tissue disease (MCTD-SS) in 7 pts.] and 38 healthy females were examined. Anti-gal(-) IgG antibodies were measured with a LEIA kit (ED055) using human gal(-) IgG as antigen. IgG-, IgA- and IgM-RF were determined with an enzyme-linked immunosorbent assay kit using human IgG-Fc as antigen. RFs were also examined by a conventional assay (laser nephelometry; LN-RF). RESULTS: Serum anti-gal(-) IgG antibody titers were higher in RA than in primary SS, SLE-SS or MCTD-SS, but the incidence of the antibodies did not differ between RA and primary SS. In both RA and primary SS, the antibodies were positive in half of the LN-RF-negative patients, and were also detected in almost all of those patients who had at least one of the RF isotypes. LN-RF, IgG-RF, IgA-RF and IgM-RF were present more frequently and their titers were higher in RA than in primary SS, but IgA-RF levels were similar in both groups. In RA-SS, all of the antibody titers were notably higher than in RA or primary SS. In RA and primary SS, IgA-RF and IgM-RF were common RF isotypes, and anti-gal(-) IgG antibody levels correlated well with LN-RF, IgA-RF and IgM-RF levels. These antibody profiles did not relate to any of the clinical parameters in RA, but all the antibody titers correlated with anti-SS-A/Ro antibody levels in primary SS. CONCLUSIONS: The anti-gal(-) IgG antibodies are not specific for RA; they are also frequent in SS. Our LEIA for antibodies is a very sensitive method to detect all RF isotypes in both RA and SS. Most of the antibody profiles are common to both diseases, although antibody titers are higher in RA, especially in RA-SS.

Adult↗

Continuous hyperthermic peritoneal perfusion for peritoneal dissemination of gastric cancer.

BACKGROUND/AIMS: We investigated the histological and clinical effectiveness of continuous hyperthermic peritoneal perfusion (CHPP) for treating peritoneal dissemination (therapeutic CHPP) and for the prevention of peritoneal recurrence (prophylactic CHPP). METHODOLOGY: In 5 patients with gastric cancer and peritoneal dissemination, the apoptosis index of the cancer cells on in situ end-labeling for detection of apoptotic cells was 3.0+/-1.2% before CHPP, and had increased to 52.9+/-8.3% after CHPP. The survival curve of the therapeutic CHPP group was significantly better than that of the control group. The therapeutic CHPP group was classified as miliary type or nodular type. The survival curve in the miliary type was significantly better than that in the nodular type. RESULTS: In prophylactic CHPP, there was no improvement in prognosis, but a prophylactic effect against peritoneal recurrence was demonstrated in the patients who were n4 negative when the mean intraperitoneal temperature during CHPP (MIT) was maintained above 42 degrees C. CONCLUSIONS: These results indicated that an improved prognosis can be expected after therapeutic CHPP in patients with peritoneal spread. The beneficial effects are especially marked in patients with the miliary type. Moreover, prophylactic CHPP exerts a prophylactic effect against peritoneal recurrence in patients with n4 negative, providing that the MIT can be maintained above 42 degrees C.

Apoptosis↗