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Biomedical subjects

R Kasukawa

Publications and source records attributed to R Kasukawa.

At least 73 records · Page 4Linked to original sources
PubMed1998

Endothelin-1 production by human synoviocytes.

Immunoreactive (ir)-endothelin (ET)-1 concentrations in serum samples and synovial fluids from patients with rheumatoid arthritis were higher than concentrations in sera obtained from healthy volunteers. No significant difference in ir-ET-1 concentrations in synovial fluid was observed between rheumatoid arthritis patients and osteoarthritis patients. Cultured fluids of synovial cells collected from synovial tissues and leucocytes from synovial fluids of rheumatoid arthritis patients were studied to determine the origin of ir-ET-1 in synovial fluids. Ir-ET-1 was detected in the cultured fluids of synovial macrophage-like type A cells, but not in those of fibroblast-like type B cells from the synovial tissues or leucocytes from the synovial fluids. Longitudinal studies showed that the ir-ET-1 concentration in the cultured fluid reached a peak around 24 h after starting the culture. ET-1 secreted from macrophage-like synoviocytes may be involved in the pathogenesis of inflammatory arthritis.

Arthritis, Rheumatoid↗
PubMed1998

Two patients with polymyositis or dermatomyositis complicated with massive pleural effusion.

Two patients with polymyositis (PM) or dermatomyositis (DM) complicated with massive pleural effusion are reported here. Both patients presented a high-grade fever, pleural effusion prominent on the right, and good response to steroid therapy. In a 50-year-old woman with PM, combined process of pleural inflammation, cardiomyopathy and coexisting hypothyroidism were considered to be responsible for the accumulation of the massive pleural effusion. However, in a 34-year-old man with DM, pleural inflammation associated with interstitial pneumonia or pleural microvasculopathy in DM was considered to be responsible for the accumulation of the massive pleural effusion.

Adult↗
PubMed1998

Primary Sjögren's syndrome complicated by sarcoidosis.

Sjögren's syndrome and sarcoidosis share several common features, such as keratoconjunctivitis sicca, swelling of parotid glands, lung involvement, cutaneous anergy, T cell-mediated immunodeficiency, an increased CD4+/CD8+ lymphocyte ratio, and association with the human leucocyte antigen (HLA)-B 8 and DR 3 haplotypes. However, only five patients with primary Sjögren's syndrome and sarcoidosis have been previously reported in the English language literature. The rare case of a 49-year-old Japanese woman with primary Sjögren's syndrome complicated by sarcoidosis is described. The serum angiotensin-converting enzyme level was increased, and histological examination of lung and skin biopsies revealed noncaseating granulomas, indicating that her primary Sjögren's syndrome was complicated by sarcoidosis.

Female↗
PubMed1998

Mixed connective tissue disease with severe pulmonary hypertension and extensive subcutaneous calcification.

The results of the autopsy of a 38-year-old female with mixed connective tissue disease who had suffered from painful subcutaneous calcification in her buttocks and extremities for 14 years and died from rapidly progressive pulmonary hypertension are reported. On autopsy, her heart and lungs revealed changes of severe pulmonary hypertension with intimal thickening and plexiform lesions in the small pulmonary arteries which had resulted in the collapse of both lungs and caused marked dilatation and hypertrophy of the right ventricle of the heart. Microscopic examinations of the subcutaneous calcified tissues indicated that the calcification may have been caused by repeated panniculitis.

Adult↗
PubMed1998

An autopsy case of Wegener's granulomatosis with pachymeningitis.

A 61-year-old woman presented with high fever, headache and left facial palsy with diplopia. Histopathological examination of the biopsied specimens taken from nasal mucosa and kidney revealed a granulomatous angiitis with giant cell infiltration. Ga-DTPA-enhanced magnetic resonance imaging (MRI) revealed a thickening of dura mater in the middle cranial fossa and tentorium cerebelli. The observed left facial and occulomotor palsy was considered to be caused by pachymeningitis associated with Wegener's granulomatosis (WG). Cyclophosphamide combined with prednisolone effectively improved the symptoms. However, the patient died of acute interstitial pneumonitis, presumably caused by cyclophosphamide. The pathohistology obtained in the autopsy revealed a fibrous thickening of the dura mater in the left meningen with a segmental scarring of the arteries and a necrotizing arteritis in the kidney.

Anti-Inflammatory Agents↗
PubMed1998

Antineutrophil cytoplasmic antibody in patients with antinuclear antibody-positive chronic hepatitis C.

UNLABELLED: Hepatitis C viral (HCV) infection has been shown to lead to autoimmune phenomena. Antineutrophil cytoplasmic antibodies (ANCA) have been known to be present in several autoimmune liver diseases. This study aimed to evaluate the prevalence of ANCA in sera of patients with antinuclear antibody (ANA)-positive chronic hepatitis C (CH-C) and to characterize ANCA antigens by Western blot compared with HCV-negative autoimmune hepatitis (AIH). METHODS: Ninety sera obtained from 20 patients with ANA-positive CH-C, 20 patients with ANA-negative CH-C, 20 patients with AIH, 6 patients with primary screlosing cholangitis (PSC) and 24 healthy controls were tested using an indirect immunofluorescence assay, cell ELISA and Western blotting to detect ANCA. RESULTS: In the indirect immunofluorescence assay, ANCA was found in 60% (12/20) of patients with ANA-positive CH-C, 100% (20/20) of patients with AIH and 33.3% (2/6) of patients with PSC, but in none of patients with ANA-negative CH-C (n = 20) or healthy controls (n = 24). The staining pattern observed in sera of these patients was a peculiar mixture of both cytoplasmic and perinuclear patterns. The mean ANCA titer by cell ELISA was significantly (p < 0.01) higher in patients with AIH compared with ANA-positive or ANA-negative CH-C patients or healthy controls. However, no correlation was found between ANCA titers and ANA titers, serum alanine amino transferase (ALT) or IgG levels in either ANA-positive CH-C or AIH. Western blots of ANCA-positive sera from ANA-positive CH-C patients revealed two bands corresponding to molecular weights of 72 and 46 kDa and there was no differencies in ANCA antigens compared with that from AIH patients. CONCLUSIONS: We found an increased incidence of ANCA in ANA-positive CH-C patients. ANCA in ANA-positive CH-C patients is thought to be one of autoimmune phenomena lead by HCV infection because no difference was observed in the epitope of ANCA antigens between patients with CH-C and AIH.

Adult↗
PubMed1998

Immunohistochemical localization of endothelin-1/big endothelin-1 in normal liver, liver cirrhosis and hepatocellular carcinoma.

In order to clarify the characteristics of cellular localization of ET-1/big ET-1 in liver tissues, we carried out immunohistochemical study on 30 normal, 87 cirrhosis (LC) and 55 hepatocellular carcinoma (HCC) liver specimens using anti-ET-1 antibody and anti-big ET-1 antibody and further performed in situ hybridization on 5 LC liver specimens. Positive immunostaining of hepatocytes of normal and LC livers, and tumor cells of HCC was obtained. The frequency of positive cells for ET-1 and big ET-1 of normal liver was very low. In contrast, LC hepatocytes were stained much more frequently for both ET-1 and big ET-1 than those of normal liver (P < 0.01). In the HCC livers hepatoma cells showed intermediate frequency of positive cells between normal and LC livers. Big ET-1, not ET-1, expression in HCC was significantly high compared with that of normal liver (P < 0.01). Specific signals for ET-mRNA were not detected in hepatocytes of LCs by in situ hybridization. ETs detected in hepatocytes by immunohistochemistry, therefore, seem not to have been synthesized locally. The origin of ETs is not clear but they might have been taken up from the circulation through ET receptors on hepatocytes. Although the clearance mechanism of ETs by ET-converting enzyme or other peptidases in liver has not been elucidated, the mechanisms seem to be absent or impaired in LC and/or HCC liver since the frequency and intensity of ET-positivity in the diseased hepatocytes are significantly high than those of normal liver. In addition, a disturbance of ET excretion into the bile may be also responsible for the ET storage. Elevation of serum ET levels in LC may be caused by disturbance of ET degradation and/or leakage of bile into the blood, as the ET is excreted through the biliary system.

Carcinoma, Hepatocellular↗
PubMed1998

Two sister cases of autoimmune hepatitis.

Two sister cases of autoimmune hepatitis are described. Case 1 involved a 49-year-old woman who suffered from bleeding gums and general fatigue. Her laboratory data showed a marked increase in transaminase levels, an elevated IgG level with titers 1:80 or more of both antinuclear and smooth muscle antibodies and thrombocytopenia. Histology of the biopsied liver revealed chronic active hepatitis with a moderate infiltration of mononuclear cells. A complication of idiopathic thrombocytopenic purpura was determined based on higher titers of PA-IgG and a normal bone marrow findings. Case 2 involved a 54-year-old woman, an elder sister of case 1, who suffered from general fatigue with jaundice. Her laboratory data showed a severe damage of liver function and an elevated IgG level with positive antibodies to nuclear and smooth muscle antigen. Histology of the biopsied liver revealed chronic active hepatitis. Both patients were negative to markers of hepatotrophic agents. Under diagnosis of autoimmune hepatitis, they have been treated with prednisone followed by a significant clinical improvement. HLA types of two patients were Bw54-DR4 and DR4. Among 4 other siblings, the eldest sister suffered from rheumatoid arthritis. The occurrence of two sister cases of type-1 autoimmune hepatitis has rarely reported and the fact would support a role of enviromental factors besides genetic factors for the onset of this disease.

Female↗
PubMed1998

[Two cases of severe adult varicella pneumonia].

Varicella pneumonia is the most common complication of adult varicella. Symptoms may be severe and the mortality rate high in patients who are immunodeficient or pregnant. Symptoms may be mild and progression more favorable in adults previously in good health. We report two cases of varicella infection complicated by severe pulmonary involvement in adult patients who were previously healthy. Case 1 was a 36-year-old male who 6 days after developing varicella was clinically observed to have dyspnea and hemopytsis. He died of acute respiratory failure on the following day. Case 2 was a 28-year-old male whose respiratory symptoms started the third day after developing varicella. These symptoms were relieved by treatment with acyclovir and gammaglobulin. Careful observation is and an early treatment of varicella should be undertaken not only for patients with suppressed cellular immunity, but also for healthy adults, to prevent severe complications.

Acute Disease↗
PubMed1998

[Two cases of adult Still's disease with atypical rash].

Adult Still's disease is a febrile disorder of unknown etiology, characterized by spiking fever, arthralgia, leukocytosis and a typical rash. However, most of these clinical findings, except for the typical rash, are not specific to this disease: therefore, the typical rash is the most important clinical finding for diagnosing this disease and physicians often have difficulty in making a definite diagnosis without the typical rash. In our department and related institutions, we have encountered 10 patients with Adult Still's disease who fulfilled the preliminary criteria for classification as Adult Still's disease, proposed by the Adult Still's Research Committee in Japan. The three major criteria are fever, arthralgia and typical rash, and 8 of 10 patients had an atypical rash; one satisfied two major criteria, and had an atypical rash and the other satisfied three major criteria and had an atypical rash on her eyelids. Here, we present the two cases of Adult Still's disease with atypical rash. The first patient was a 36-year-old male with an itchy annular erythema chronicum migrans, frequently seen inpatients with Lyme's disease, on his back. His clinical symptoms improved and the erythema disappeared after treatment with corticosteroids. The second patient, a 17-year-old female, had three major findings. In addition to the typical rash on her face, she had a heliotrope rash, usually seen in patients with dermatomyositis, on her eyelids. The typical rash on her face was related to her other clinical manifestations, and improved after treatment with corticosteroids. However, the rash on her eyelids showed no improvement after steroid therapy, suggesting that the erythema was probably not related to Adult Still's disease. Typical rash in Adult Still's disease, defined as a macular or maculopapular nonpruritic salmon pink eruption, was demonstrated to have the highest relative value associated with relatively high sensitivity and specificity for the diagnosis of Adult Still's disease. However, we have to be aware that some patients with Adult Still's disease could also have an atypical rash.

Adolescent↗
PubMed1997

Synovial mononuclear cells consist with T cells which produce high levels of tumor necrosis factor alpha.

To determine whether synovial mononuclear cells include a population of tumor necrosis factor alpha-producing T cells, we measured tumor necrosis alpha levels in culture supernatants of synovial mononuclear cells by ELISA and analyzed tumor necrosis alpha mRNA-positive cell frequencies. There were no significant differences in the spontaneous levels of TNF alpha between synovial mononuclear cells and peripheral mononuclear cells. The frequency of tumor necrosis factor alpha mRNA-positive cells in synovial mononuclear cells was higher than that of peripheral mononuclear cells. When stimulated with a superantigen, mononuclear cells from the synovial fluid of rheumatoid arthritis patients showed higher levels of tumor necrosis factor alpha production (1,035 +/- 817 pg/ml) than did mononuclear cells from their peripheral blood (236 +/- 180 pg/ml). In addition, we observed that a few T cell clones were resistant to superantigenic restimulation in vitro. We conclude that when these types of T cells persist in the synovium, they play a role in the development of rheumatoid arthritis via a mechanism involving tumor necrosis factor alpha production.

Animals↗
PubMed1997

Granulocytapheresis in the treatment of patients with rheumatoid arthritis.

The G-1 column is an extracorporeal type granulocytapheresis device packed with 220 g cellulose acetate beads to which granulocytes and monocytes specifically adhere. A total of 59 rheumatoid arthritis patients with elevated granulocyte counts from 4 hospitals in Japan received 2 apheresis sessions of 1 h duration/week for a total of 8 times over a period of 4 weeks. About 55% of the leukocytes which entered the G-1 column were adsorbed onto the beads: 95% were granulocytes, 3.5% monocytes, and 0.4% lymphocytes. Clinical and efficacy assessments showed improvements in swollen joints (p < 0.01), tender joints (p < 0.001), the active joint score (p < 0.001), duration of morning stiffness (p < 0.01), and grip strength (p < 0.001). In good responders, the improvements were observed for up to 12 weeks following the last apheresis. Exacerbation was noted in 2 patients. It is suggested that the efficacy of the G-1 column is attributable to the removal or suppression of hyperactive leukocytes and inflammatory cytokines, inducing a kind of immunomodulation.

Adsorption↗
PubMed1997

Enhanced interleukin-8 production by cultured Chang liver cells subjected to ethanol exposure and subsequent stimulation with tumor necrosis factor-alpha.

We investigated the production of interleukin-8 (IL-8) and chemotactic activity released from Chang liver cells subjected to long-term treatment with ethanol (Et) and subsequent stimulation with tumor necrosis factor-alpha (TNF-alpha). Chang liver cells were cultured in the presence of 5, 50 or 100 mmol/l Et for 4 weeks and then treated with recombinant TNF-alpha (1, 10, 100 U/ml). The culture supernatants were assayed for IL-8 using a sandwich ELISA and chemotactic activity was measured using a chemotactic chamber. Total RNA was also extracted from these cells and IL-8 mRNA was assayed by RT-PCR. In addition, TNF-receptor expression on the Et-treated cells was analyzed by flow cytometry. IL-8 levels in supernatants of cells stimulated with 100 U/ml of TNF-alpha for 48 h rose significantly with increasing concentrations of Et and values obtained were as follows: 4,918 +/- 244.4 pg/ml at 0 mmol/l Et, 5,335 +/- 266.2 pg/ml at 5 mmol/l Et, 8,726 +/- 873.4 pg/ml at 50 mmol/l Et and 9,134 +/- 866.0 pg/ml at 100 mmol/l Et. The chemotactic activity also increased with increasing concentrations of Et and was almost completely suppressed by anti-IL-8 antibody. Using semiquantitative analysis of radioactivity of IL-8 mRNA using a 32P gamma ATP-labeled primer for IL-8 mRNA, Et-treated cells were shown to have markedly higher levels of radioactivity than untreated cells. In addition, TNF-receptor expression was significantly higher in cells treated with 100 mmol/l Et. These data suggest that long-term Et treatment of Chang liver cells stimulated with TNF-alpha may enhance transcription of the IL-8 gene with up-regulation of the TNF receptor.

Antibodies↗
PubMed1997

Synoviocyte proliferation in joints of SCID mice induced by toxic shock syndrome toxin-1 stimulated T cells from patient with rheumatoid arthritis.

OBJECTIVE: To investigate the histopathological arthropathy in severe combined immunodeficient (SCID) mice given intraarticular injection of toxic shock syndrome toxin-1 (TSST-1) stimulated T cells from patients with rheumatoid arthritis (RA). METHODS: Unstimulated or TSST-1 stimulated T cell blasts (TB-TSST) of synovial fluid mononuclear cells from patients with RA (RASFMC) were intraarticularly injected into the knee joint of SCID mice. Four weeks later, the knee joints were histopathologically examined and the numbers of fibroblasts in the synovial tissues were compared with those of controls. Total RNA of the SCID mouse knee joints was isolated and Southern analysis for human T cell receptor (TCR) V beta 2 and human tumor necrosis factor-alpha (TNF-alpha) was carried out. RESULTS: Hyperplasia and increased numbers of the fibroblasts as well as neovascularization of the synovial tissues were observed in the SCID mouse knee joint tissues injected with TB-TSST of RASFMC compared with those injected with unstimulated T cells from RASFMC or with TB-TSST from peripheral blood of healthy controls. Messenger RNA for human TCR V beta 2 and TNF-alpha were detected in the SCID mouse knee joint tissues injected with TB-TSST from RASFMC. CONCLUSION: Superantigen TSST-1 stimulated T cells from RASFMC have the ability to induce chronic arthropathy with fibroblast proliferation and neovascularization in the SCID mouse.

Animals↗
PubMed1997

Anti-endothelial cell antibodies in the sera of patients with mixed connective tissue disease--the clinical significance.

To determine the clinical significance of anti-endothelial cell antibodies in mixed connective tissue disease (MCTD), we measured the titers of antibodies to both untreated and cytokine-treated endothelial cells (EC) in the sera of the MCTD patients by means of an enzyme linked immunosorbent assay. The mean titer of antibodies to untreated EC (aEC) in the sera of the MCTD patients was significantly higher than that for the healthy subjects. The mean titer of antibody to EC treated with IFN gamma, IL1 (aIL1-EC) or TNF alpha (aTNF-EC) was significantly higher than that of aEC in the sera of the MCTD patients with proteinuria, and the mean titer of aTNF-EC was significantly higher than that of aEC in the sea of the MCTD patients with pulmonary fibrosis. Furthermore, the mean titers of aIL1-EC and aTNF-EC in the sera of the MCTD patients with pulmonary fibrosis were significantly higher than those of aIL1-EC and aTNF-EC in the sera of the MCTD patients without pulmonary fibrosis. These results suggest that antibodies to cytokine-treated EC may play a more important role in the manifestation of renal or pulmonary lesions in MCTD patients than aEC.

Antibodies↗
PubMed1997

Expression of Fas antigen on hepatocytes in viral hepatitis patients.

To evaluate the relationship between viral hepatitis and apoptosis, expression of Fas antigen in liver tissue sections of patients with viral hepatitis was investigated by immunohistochemical study using antibody to Fas antigen. A total of 46 liver tissues were obtained from 12 patients with acute viral hepatitis (AH) and 34 patients with chronic hepatitis (CH). Fas antigen was more markedly expressed in hepatocytes of AH patients than of CH patients. The Fas-positive hepatocytes of AH patients was localized rather diffusely in the inter lobular area and they were associated with closely to the area of the inflammatory cell infiltration. In CH patients, Fas antigen was weakly expressed in hepatocytes and was more intense in chronic active hepatitis than in persistent hepatitis patients. These results indicate that apoptosis may occur more frequently in AH than CH and might contributed to death of hepatocytes mainly in viral AH and partly in viral CH.

Adult↗