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Biomedical subjects

R Kasukawa

Publications and source records attributed to R Kasukawa.

At least 145 records · Page 8Linked to original sources

Crossreactivity of anti-cardiolipin antibodies with glycolipids and endothelial cells.

To investigate the crossreactivity of anti-cardiolipin antibodies (aCL) with glycolipids and endothelial cells, we used (1) culture supernatants derived from Epstein-Barr virus (EBV)-transformed peripheral lymphocytes of patients with systemic lupus erythematosus (SLE) complicated by antiphospholipid syndrome, and also (2) sera from patients with SLE. The results obtained from culture supernatants demonstrated that aCL crossreacts with myelin-derived acidic glycolipid sulfatide, bacterial endotoxin glycolipid lipid A and human umbilical vein endothelial cells (HUVEC). The results obtained from sera showed a significant correlation between levels of aCL and anti-sulfatide antibody, and between levels of aCL and anti-HUVEC antibody. These findings indicate that aCL can bind to the myelin sheath and HUVEC, which may have implications for the pathogenic potential of aCL for nervous system involvement and thrombotic complications.

Antibodies, Anticardiolipin↗

Henoch-Schönlein purpura associated with pregnancy in a patient with chronic thyroiditis.

A case of Henoch-Schönlein purpura with chronic thyroiditis associated with pregnancy is reported. A 27-year-old woman had a struma since age 14. She felt easily fatigable along with enlargement of the struma after the delivery of her first child, and was diagnosed as having chronic thyroiditis. She developed hematuria between the first delivery and the second pregnancy. The hematuria continued during the second pregnancy and in the postpartum period. Immediately after the delivery of her second child, she developed purpura followed by arthralgia and melena. Renal biopsy revealed focal segmental and global type Henoch-Schönlein nephritis. We reviewed five cases of Henoch-Schönlein purpura associated with pregnancy and found that our case is the first in which purpura developed immediately after delivery. Our patient would have developed Henoch-Schönlein nephritis between the first delivery and the second pregnancy. She developed Henoch-Schönlein purpura possibly due to rebound activation of immune response in the postpartum period after the disappearance of dramatic suppression of both humoral and cell-mediated immunity in the pregnant period.

Adult↗

[A case of systemic lupus erythematosus in late component (C9) complement deficiency].

We report on a case of C9 deficiency followed by the onset of systemic lupus erythematosus (SLE). A 51-year-old female patient had suffered from repeated urinary tract infections since 1977. In 1980, at 41 years of age, she had proteinuria and facial erythema along with low level of CH50 less than 12.0 U/ml. She was diagnosed as C9 deficiency (C9D) because of C9 protein less than 0.5 mg/dl, C9 activity 0.03% and C8 activity 94% and also SLE was strongly suspicious. Subsequently, she suffered from repeated urinary tract infections. In 1990, she was diagnosed as SLE because of pleuritis, pericarditis and positive anti-nuclear (1:640) and positive anti-DNA antibody (28.0 U/ml) in addition to proteinuria and facial erythema. From the family study, her two sisters showed homozygous C9D (less than 0.5 mg/dl) with hypergammaglobulinemia (2290 and 2230 mg/dl, respectively) and positive anti-nuclear antibody (1:80) in both. Her father also showed heteropygous C9D (1.7 mg/dl) with anti-nuclear antibody (1:640). These results suggest that healthy carriers of C9D may have some abnormalities in humoral or cell-mediated immunity. The possibility was thought that other unrecognized disease associated loci exist in linkage with the C9 allele like that of C4D was speculated. And repeated infections due to C9D may possibly induce B cell activation followed by the occurrence of SLE or related disorders. This case seems to be very valuable with respect to the onset of SLE under a long-term observation of C9D.

Complement C9↗

[Association of autoimmune disease in primary biliary cirrhosis].

Association of autoimmune disease in patients with primary biliary cirrhosis (PBC) was described. Forty-one patients with asymptomatic PBC (a-PBC) and 13 patients with symptomatic PBC (s-PBC) were examined. The overall prevalence of autoimmune disease in association with PBC was 63%. There was no significant difference in the frequency of autoimmune disease association between a-PBC (63.4%) and s-PBC (61.5%). The most frequent complication was Sjögren's syndrome (31.7% in a-PBC and 38.5% in s-PBC). Raynaud's phenomenon was seen in 7 patients (12.2% in a-PBC and 15.4% in s-PBC). Five of these 7 patients showed the CREST syndrome having the anti-centromere antibody. Association of 3 polyarthritis, 2 autoimmune hepatitis, 2 Hashimoto's disease, 1 systemic lupus erythematosus, 1 polymyositis and 1 temporal arteritis was seen in a-PBC patients.

Adult↗

Detection and epitope analysis of autoantigen-reactive T cells to the U1-small nuclear ribonucleoprotein A protein in autoimmune disease patients.

T cells that recognize autoantigens might play an important role in autoimmune diseases. To analyze "autoantigen-reactive T cell" in patients with an autoimmune disease, a human lymphocyte proliferation assay using soluble recombinant autoantigens has been conducted. PBMC from mixed connective tissue disease and SLE patients who possessed anti-U1-small nuclear ribonucleoprotein (snRNP) A autoantibodies responded to a recombinant U1-snRNP A protein. In contrast, PBMC from healthy subjects or autoimmune disease patients not possessing anti-U1-snRNP A autoantibodies did not show such responses. In addition, this proliferative response was inhibited by anti-CD4 mAb. Limiting dilution analyses revealed that the autoantigen-reactive T cells exist in relatively high frequency (1 of 4,065 to 1 of 23,256) in the mixed connective tissue disease patients. Moreover, by T cell epitope mapping, the T cell epitope area was found to be located in the C-terminus of the U1-snRNP A protein, overlapping the B cell epitope area that has been reported. These findings suggest the presence of autoantigen-reactive T cells in such patients, and when these T cells are activated, they may play a central role in the autoantibody generation.

Amino Acid Sequence↗

Detection of hepatitis C virus genome in human serum by multi-targeted polymerase chain reaction.

A multi-targeted "hemi-nested" PCR (M-PCR) assay in which the primer pairs derived from the 5' non-coding (5'NC) and the nonstructural protein 3 (NS3) regions of HCV genome were concurrently used for amplification in order to compare the sensitivity and specificity of polymerase chain reaction (PCR) with different primer pairs in detecting hepatitis C virus (HCV) genome. Sera from patients with virus-associated liver diseases were examined for the presence of HCV RNA by the M-PCR method following reverse transcription to cDNA. The amplified products derived from both the 5'NC and the NS3 regions were detected in 28 (70%) of the 40 HCV RNA-positive samples. However, 12 samples (30%) were devoid of the signal of NS3-derived product. Sensitivity tests using serial dilutions of HCV RNA revealed that the 5'NC-derived band was still detectable in the 10(5)-fold diluted sample by the M-PCR method, yet the NS3-derived band could hardly be detected in the 10(4)-fold diluted sample. Thus, as previously demonstrated by a single-targeted "nested" PCR assay, the present study using the M-PCR assay has clearly shown that the 5'NC-derived primers are more sensitive and specific than the NS3-derived primers in detecting HCV RNA.

BK Virus↗

An autopsy case of ulcerative colitis associated with Takayasu's disease with a review of 13 Japanese cases.

An autopsy was performed on a 42-year-old Japanese female who had been suffering from both ulcerative colitis (UC) and Takayasu's disease. Her UC started at age 27 with bloody stool, and Takayasu's disease was diagnosed at age 30 on the basis of absence of pulse in her left arm. After more than ten years she died of multiple cerebral infarction. An autopsy study revealed the scarring stage of UC in the entire colon and aortitis in the aortic arch and its major branches and pulmonary arteries. Her HLA type was positive for HLA-A2, 24, Bw52 and 61. Clinical features of a total of 13 Japanese cases that had both UC and Takayasu's disease have been reviewed in the Japanese and Western literature.

Adult↗

Complement activating properties of monoreactive and polyreactive IgM rheumatoid factors.

OBJECTIVES: To estimate the complement activating properties of monoclonal, monoreactive, and polyreactive IgM rheumatoid factors derived from Epstein-Barr virus transformed B cells isolated from peripheral blood and synovial tissue of patients with rheumatoid arthritis (RA). METHODS: An enzyme linked immunosorbent assay (ELISA) was used to measure the activation of the classical pathway of complement by monoclonal IgM rheumatoid factor. Monoclonal IgM rheumatoid factor was bound to IgG Fc adsorbed onto microtitre plates and then reacted with diluted normal human serum as a source of complement. The activation and binding of C4 were measured with F(ab')2 antibody to human C4. The complement activating property of IgM rheumatoid factor bound to IgG Fc was tentatively expressed as the ratio of the amount of bound C4 to the amount of bound IgM rheumatoid factor. RESULTS: The complement activating property of monoreactive IgM rheumatoid factor was shown to be about three times higher than that of polyreactive IgM rheumatoid factor. CONCLUSIONS: Monoreactive IgM rheumatoid factor with the higher complement activating property would result in a greater degree of complement dependent inflammation and might have a more important pathogenic role in RA than polyreactive IgM rheumatoid factor.

Adult↗

Anticardiolipin antibodies are associated with pulmonary hypertension in patients with mixed connective tissue disease or systemic lupus erythematosus.

Anticardiolipin antibodies (aCL) were studied in relation to pulmonary hypertension (PH) in 22 patients with mixed connective tissue disease (MCTD) or systemic lupus erythematosus (SLE). The mean pulmonary arterial pressure (mPAP) values were similar in the 12 MCTD and 10 SLE patients: 26 +/- 11 and 25 +/- 11 mm Hg, respectively. However, the frequency of PH was higher in SLE (60%) than in MCTD patients (33%). The titers of aCL were significantly higher in SLE (38 +/- 27 IU/ml) than in MCTD (17 +/- 7 IU/ml; p < 0.02). Two SLE patients with high titers of aCL had multiple cerebral infarction and transverse myelitis, and deep vein thrombosis, respectively. A significant correlation between the titers of aCL and mPAP was observed in patients with MCTD (p < 0.05), but not in patients with SLE.

Adult↗

Rheumatoid factor: a review of the mode of formation and role in transplantation.

The mode of formation and role of rheumatoid factors (RF) in transplantation were reviewed. RF might be produced through stimulation with altered transplantation antibody, which undergoes conformational changes resulting from the reaction with a graft. Some recipients might have such sources of infection as cytomegalovirus or human herpes virus 6 (HHV-6), because almost all patients were treated with immunosuppressive agents. Many bacteria and viruses have IgG Fc receptors on their surface. Herpes virus infection, such as herpes simplex virus, has been demonstrated to be capable of expressing Fc receptor on the infected cells. These Fc receptors could produce RF through the response of antibody production to anti-idiotype of Fc receptors. Also, IgG, which binds to Fc receptors, changes conformationally to produce RF. RF can also be produced as a result of graft versus host reaction. Although IgG RF reacting with homologous IgG is believed to have the most important role in pathogenic conditions, they have not been studied because of difficulties in their measurements. We developed an enzyme immunoassay for detection of IgG RF combining with homologous IgG. The wells of an assay plate were coated with Fc fragment of human IgG, and after incubation with tested serum, binding of IgG RF to the Fc was detected by means of goat anti-human IgG F (ab')2 antibodies followed by alkaline phosphatase conjugated rabbit anti-goat IgG and substrate. IgG RF were increased significantly more in transplantation sera of patients who rejected grafts than in those of patients who had satisfactory graft function. Some evidence for the role IgG RF in rejection, even if only circumstantial, has been provided.

Animals↗

[A case of Sjögren's syndrome accompanied by lymphadenopathy and IgG4 hypergammaglobulinemia].

A 78-year-old male patient suffered from slight dryness of his mouth and eyes, which was followed by swelling of the parotid and submandibular glands on both sides. Subsequently, he developed generalized lymphadenopathy accompanied by hypergammaglobulinemia IgG 7740 mg/dl, main subclass: IgG4, 5800 mg/dl. Histopathological examination of lymph nodes from his left neck showed follicular proliferation of plasma cells containing cytoplasmic kappa and lambda chains of IgG4, without destruction of the lymph node structure. His serum showed very low levels of complement: 0 U/ml of CH 50, 14 mg/ml of C3 and less than 11 mg/ml of C4. During treatment with prednisolone at 30 mg/day, the swelling of the salivary glands and lymph nodes reduced the IgG and IgG4 decreased and the complement increased. Finally, all lymph nodes, IgG and complement abnormalities were normalized. Anticomplementariness of IgG4 was demonstrated in this patient.

Aged↗

Pulmonary hypertension in MCTD: report of two cases with anticardiolipin antibody.

We report on 2 patients with well-documented mixed connective tissue disease (MCTD) accompanied by severe pulmonary hypertension (PH) due to thrombosis or thromboembolism. In a previous report we indicated (1) that patients with MCTD complicated by PH have a significantly worse prognosis than patients with other connective tissue disease (CTD) complicated by PH. Both our patients had anticardiolipin antibody (a-CL) in the initial stages of the disease. We also studied the relationship of a-CL to PH in patients with other CTD. Patients of either MCTD or SLE with high levels of a-CL had significantly higher values of mean pulmonary arterial pressure than patients without a-CL. Several factors were suggested for the pathogenesis of PH such as vasospasm, arteritis, platelet dysfunction, and thrombosis or thromboembolism. The presence of a-CL may be one of important factors in development of PH among patients with MCTD with recurrent pulmonary thrombosis or thromboembolism.

Adult↗

Risk factors in the pregnancy of patients with systemic lupus erythematosus: association of hypocomplementaemia with poor prognosis.

Fetal wastage is still high in the pregnancies of patients with systemic lupus erythematosus (SLE). We examined retrospectively the cases of 38 patients with inactive SLE in whom pregnancy was either desired or had already been obtained. The prevalence of antiphospholipid antibodies in the group with fetal loss was high. The antibodies were, however, also detected in five of 14 patients who had had a live birth. It was noted that low levels of serum complement activity (CH50 less than 25 U/ml) occurred in five of six patients with fetal loss, but in only two of 22 with a live birth. Serial studies also confirmed a close association between decreased serum complement activity and poor fetal prognosis in lupus pregnancy. Treatment with increased doses of prednisolone may help to achieve successful live births. Thus hypocomplementaemia may be associated with a worse prognosis for the fetus in the pregnancies of some patients with SLE in remission.

Adult↗