Search PubMed⌕ Search

Biomedical subjects

R Kasukawa

Publications and source records attributed to R Kasukawa.

At least 55 records · Page 3Linked to original sources
PubMed1999

Suppressive effect of prostaglandin E1 on pulmonary hypertension induced by monocrotaline in rats.

The effect of administering prostaglandin E1 (PGE1) on the extent of monocrotaline (MCT)-induced pulmonary hypertension and cytokine production [interleukins (IL) 1 and 6 and tumor necrosis factor (TNF)] by macrophages during MCT induction of pulmonary hypertension was studied. Right ventricle/left ventricle plus septum weight ratios (RV/LV + S) were used as an index of the development of pulmonary hypertension. Administering PGE1 at a dose of 0.2 mg/kg/day for 4 weeks reduced significantly the RV/LV + S ratio from 0.428 +/- 0.070 to 0.243 +/- 0.059 (p < 0.01) and decreased the production of these cytokines: IL-1, from 4.675 +/- 3.558 to 1.800 +/- 0.722 units; IL-6, from 0.322 +/- 0.121 to 0.060 +/- 0.039 units; and TNF, from 0.578 +/- 0.369 to 0.004 +/- 0.004 units. In another series of experiments, a significant reduction of the RV/LV + S ratio was noted for only 1 week when we administered PGE1 immediately after the injection of MCT. We confirmed that histopathologic improvements of lungs were noted by administering 0. 2 mg/kg PGE1 for 4 weeks. In another experiment, PGE1 at a concentration of 2 microg/ml suppressed a rise in the cytosolic Ca2+ concentration of lipopolysaccharide-stimulated peritoneal macrophages of rats in vitro, suggesting that PGE1 suppressed cytokine production by macrophages through the suppression of the Ca2+ influx. These results suggest that administering PGE1 may be effective in the treatment of some forms of pulmonary hypertension in humans.

Alprostadil↗
PubMed1999

Immunohistological study endothelin-1 and endothelin-A and B receptors in two patients with scleroderma renal crisis.

Scleroderma renal crisis (SRC) developed in two patients with systemic sclerosis (SSc) and they died from respiratory failure. Findings on autopsy revealed congestion and oedema in both lungs and intimal thickening of the small renal arteries in both patients. Immunohistological investigations showed positive staining of anti-human endothelin (ET)-1 in the media of the small renal arteries and ET-B receptor in the medial smooth muscle of the small renal arteries. This observation suggests an important pathophysiological role of ET-1 in the development of SRC in some patients with SSc.

Acute Kidney Injury↗
PubMed1999

Clinico-laboratory characteristics of patients with dermatomyositis accompanied by rapidly progressive interstitial lung disease.

The clinico-laboratory features of 16 patients with dermatomyositis (DM) were compared between patients with accompanying rapidly progressive interstitial lung disease (RP-ILD, n = 7) and those with chronic interstitial lung disease (C-ILD, n = 9), and also between deceased (seven RP-ILD and three C-ILD) and living patients (six C-ILD). The extent of muscle weakness of the extremities and frequency of autoantibody positivity were significantly lower in DM patients with RP-ILD than in DM patients with C-ILD. Furthermore, significantly lower serum creatine kinase/lactate dehydrogenase levels (0.26+/-0.27) were found in the 10 patients who died than in the six living patients (1.21+/-1.09). A higher CD4+/CD8+ T-lymphocyte ratio in the peripheral blood (3.51+/-2.65) was detected in the four DM patients with RP-ILD who died than in the six living DM patients with C-ILD (1.22+/-0.49).

Adult↗
PubMed1999

EUS analysis of collateral veins inside and outside the esophageal wall in portal hypertension.

BACKGROUND: The relation between esophageal varices and venous collaterals outside the esophageal wall in patients with portal hypertension remains unclear. We investigated this relationship with endoscopy and endoscopic ultrasound (US). METHODS: Twenty-two patients with untreated varices were examined. The collaterals were studied with a 20 MHz US catheter probe. Collaterals were divided into two groups: (1) periesophageal collateral veins adjacent to the muscularis externa of the esophagus and (2) paraesophageal collateral veins external to the esophageal wall but without contact with the muscularis externa. Periesophageal and paraesophageal collateral veins were scored as mild or severe according to stage of development. RESULTS: Varix form as defined endoscopically was significantly larger in the severe periesophageal collateral veins group than in the mild periesophageal collateral veins group (p < 0. 01). In contrast, varix form did not differ significantly between the mild and severe paraesophageal collateral veins groups. Perforating veins were detected in the distal esophagus in 18 of 22 patients (81.8%) by means of US. The prevalence of perforating veins increased in relation to varix form. Two types of perforating veins were found on the basis of connection with periesophageal and paraesophageal collateral veins. The frequency with which perforating veins were connected to periesophageal collateral veins was 81.8%; the frequency of connection to paraesophageal collateral veins was 27.3%. CONCLUSION: Periesophageal collateral veins play a more important role in the formation of esophageal varices than do paraesophageal collateral veins.

Adult↗
PubMed1999

Characterisation of T cell clonotypes that accumulated in multiple joints of patients with rheumatoid arthritis.

OBJECTIVE: To investigate whether identical T cell clonotypes accumulate in multiple rheumatoid joints, the clonality of T cells that had infiltrated into synovial tissue (ST) samples simultaneously obtained from multiple joints of patients with rheumatoid arthritis (RA) was analysed. METHODS: T cell receptor (TCR) beta gene transcripts, amplified by reverse transcription-polymerase chain reaction from ST and peripheral blood lymphocytes of five RA patients, were subjected to single strand conformation polymorphism analysis and DNA sequencing. RESULTS: Approximately 40% of accumulated T cell clonotypes found in one joint of a patient were found in multiple joints in the same patient. Furthermore, identical amino acid sequences were found in TCR beta junctional regions of these clonotypes from different patients with at least one HLA molecule match. CONCLUSIONS: The T cell clonotypes accumulating in multiple rheumatoid joints may be involved in the perpetuation of polyarthritis by reacting to antigens common to these multiple joints.

Amino Acid Sequence↗
PubMed1999

Primary biliary cirrhosis associated with painless thyroiditis.

A case of anti-mitochondrial antibody (AMA)-negative primary biliary cirrhosis (PBC) associated with painless thyroiditis is reported in a 47-year-old woman who diagnosed as PBC based on her elevated serum gamma-glutamyl transpeptidase and immunoglobulin M levels, as well as histological findings of destroyed bile ducts surrounded by mononuclear infiltrates in the biopsied liver. She was negative for AMA and had a depressed level of thyroid-stimulating hormone accompanied by increased free thyrosine, thyroxine and triiodothyronine levels and low titers of anti-microsomal and anti-thyroid peroxidase antibodies. Her thyroid disorder corresponded with painless thyroiditis. An association between PBC and hyperthyroidism is rare. Furthermore, an association between AMA-negative PBC and hyperthyroidism due to painless thyroiditis has not previously been reported.

Autoantibodies↗
PubMed1999

Cytophagic histiocytic panniculitis improved by combined CHOP and cyclosporin A treatment.

In a 31-year-old Japanese man with cytophagic histiocytic panniculitis (CHP) remission was achieved by a combination of combined chemotherapy CHOP and cyclosporin A treatment. He was admitted to our hospital in January 1994 with recurrent high fever of 40.2 degrees C and tender and violaceous subcutaneous nodules on his trunk, arms and legs. He developed pancytopenia, hemorrhagic diathesis, liver dysfunction. Histological examination of the biopsied subcutaneous nodule revealed a lobular panniculitis with fat necrosis and a massive infiltration of histiocytes phagocytosing nuclear debris. He was treated initially with 40 mg/day prednisolone. However, following a reduction in prednisolone dosage, his symptoms reappeared. CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) therapy was then initiated. Three courses of CHOP treatment alleviated his symptoms and cyclosporin A was used to maintain his condition for 15 months. His medication was then discontinued and he has been in complete remission for 10 months. Combined treatment of cyclosporin A and CHOP combined chemotherapy was shown to be effective for this patient with severe CHP.

Adult↗
PubMed1999

Mixed connective tissue disease.

Mixed connective tissue disease deserves to be a distinct disease entity due to the persistent citation of this disease in the literature since the original description by Sharp in 1972, in spite of the presence of several criticisms against the independency of this disease. The characteristic features of mixed connective tissue disease are: 1) the presence of anti-U1snRNP antibody with high titers in sera, 2) an increased frequency of HLA-DR4 in the leukocytes, and 3) death due to pulmonary hypertension.

Autoantibodies↗
PubMed1999

IgG 1 subclass specificity for IgG rheumatoid factors in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the significance of IgG rheumatoid factors (IgG RF) in the pathogenesis of rheumatoid arthritis (RA), and to determine the specificity of IgG subclasses binding with IgG RF in RA (RA IgG RF) compared to IgG RF in normal subjects (NS IgG RF). METHODS: The reactivities of RA IgG RF and NS IgG RF for various IgG subclasses were studied by ELISA and inhibition assay, using purified IgG heavy chains of different IgG subclasses. RESULTS: In ELISA, the optical density (OD) value of the reaction of RA IgG RF with IgG 1 was significantly higher than with IgG 2, 3, or 4 (p < 0.01). Similarly, the OD value of the reaction of NS IgG RF with IgG 1 was significantly higher than with IgG 2 or 4 (p < 0.05). In the inhibition assay, the OD value of the reaction of RA IgG RF was decreased by IgG 1, 2, and 3 (p < 0.01), but not by IgG 4. The extent of inhibition by IgG 1 was significantly greater than that by IgG 2, 3, or 4 (p < 0.05). In contrast, the OD value of the reaction of NS IgG RF was not significantly inhibited by any of the IgG subclasses. CONCLUSION: RA IgG RF and NS IgG RF reacted most strongly with IgG 1. From the differences in reactivities between RA IgG RF and NS IgG RF in the inhibition assay, it can be inferred that RA IgG RF exhibits higher affinity for IgG than NS IgG RF.

Antibody Specificity↗
PubMed1999

Significance of endogenous heat shock protein in adjuvant arthritis.

OBJECTIVE: To investigate the role of endogenous heat shock protein (HSP) (rat 60 kDa HSP, rHSP 60) in adjuvant arthritis (AA), the expression of rHSP 60 in AA-susceptible Lewis rats and AA-resistant Fisher rats was studied. METHODS: The extent of arthritis was assessed by measuring footpad thickness. The proliferative response of mononuclear cells (MNC) to mycobacterial 65 kDa HSP (mHSP 65) was measured by [3H] thymidine incorporation. The messenger RNA for rHSP 60 was quantified by dot blot hybridization in peripheral blood mononuclear cells (PBMNC), splenic MNC (SMNC), and ankle joint synovial membrane (SM). RESULTS: In Lewis rats: AA developed on Day 14 after immunization with Freund's complete adjuvant. Proliferative responses of PBMNC and SMNC to mHSP 65 were observed on Day 14 and thereafter according to the development of AA. Messenger RNA levels of rHSP 60 in PBMNC, SMNC, and SM did not increase until Day 21. In Fisher rats: AA and proliferative response of MNC to mHSP 65 were not observed throughout the observation period. Messenger RNA levels of rHSP 60 were significantly higher in preimmune Fisher rats than those in preimmune Lewis rats. Messenger RNA levels of rHSP 60 in PBMNC and SMNC increased significantly on Day 7 and decreased to preimmune levels until Day 21. CONCLUSION: We propose that elevated levels and rapid elevation of endogenous HSP 60 levels relate to resistance to AA in Fisher rats; however, lower levels and delayed increase of endogenous HSP 60 levels relate to susceptibility to AA in Lewis rats.

Animals↗
PubMed1999

Rhabdomyolysis and aggravation of arthritis in a rheumatoid arthritis patient as a result of sepsis due to Staphylococcus aureus infection of a rheumatoid nodule; a catastrophic outcome.

A 63-year-old man with rheumatoid arthritis presented with rhabdomyolysis and intractable arthritis of acute onset. He was diagnosed to have sepsis due to Staphylococcus aureus infection through of an ulcerated rheumatoid nodule. Staphylococcus aureus isolated from pus in the ulcerated rheumatoid nodule and a blood sample obtained from the heart post-mortem produced the toxic shock syndrome toxin-1 (TSST-1). The TSST-1 and/or unmethylated CpG motifs in the oligonucleotides present in a bacterium, Staphylococcus aureus in this case, might be implicated in the induction of rhabdomyolysis and intractable arthritis.

Arthritis, Rheumatoid↗
PubMed1999

CpG motif-containing DNA fragments from sera of patients with systemic lupus erythematosus proliferate mononuclear cells in vitro.

OBJECTIVE: To characterize DNA in sera of patients with systemic lupus erythematosus (SLE) in terms of size, guanine plus cytosine (G+C) content (by percentage), CpG dinucleotide (CpG) (percentage), and effects on mononuclear cells (MNC). METHODS: Nine DNA clones were sequenced. Oligodeoxynucleotides with the characteristic CpG motif (TTCGAA or PuPuCGPyPy) were examined for their proliferative effect on MNC by [3H]thymidine incorporation, expression of HLA-DR and intercellular adhesion molecule (ICAM)-1 on monocytes by flow cytometry, and mRNA levels encoding interleukin 12 (IL-12) and interferon-gamma (IFN-gamma) by semiquantitative reverse transcription polymerase chain reaction. RESULTS: The size of DNA clones ranged from 87 to 318 bp (mean +/- SD, 177+/-68) and enrichment in G+C and CpG ranged from 34.7 to 69.7% (48.1+/-10.7) and 0.63 to 12.8% (4.0+/-4.1), respectively. Three of 9 clones contained the characteristic CpG motif. Oligonucleotides proliferated MNC, and augmented HLA-DR and ICAM-1 expression in company with an increase of mRNA encoding IL-12 and IFN-gamma. CONCLUSION: Circulating CpG motif-containing DNA fragments in SLE increased mRNA encoding IL-12 and IFN-gamma, which in turn increased HLA-DR and ICAM-1 on monocytes, resulting in MNC proliferation. This mechanism could contribute to the pathogenesis of SLE.

Base Sequence↗
PubMed1998

Clinical and basic studies on the G-1 column, a new extracorporeal therapeutic device effective in controlling rheumatoid arthritis.

The G-1 column, which is filled with cellulose acetate spherical beads of 2 mm diameter, is a new type of extracorporeal perfusion device originally designed to remove granulocytes from the venous circulation of patients with rheumatoid arthritis. A dramatic improvement in clinical symptoms was seen after treatment with the G-1 column in two successive clinical trials. Early effects include pain relief, reduction in the swollen joints, and a continued decrease in inflammation as a late effect. The results were further confirmed in the adjuvant arthritic rat model. G-1 beads adsorb some amounts of platelets at the beginning and then about a quarter of circulating neutrophils, monocytes, natural killer cells, and B cells, but not T cells. Various factors released from blood cells during transit through the column must have influenced the cells including lymphocytes which passed through the column. G-column actually eliminates some parts of aggressive leukocytes, but a more interesting story is the modification of blood components, which occurred in the G-1 column, and when returned to the patients, may have ameliorated the unbalanced homeostatic network and induced acceleration of healing.

Animals↗
PubMed1998

Analysis of peripheral blood mononuclear cell stimulated with pyruvate dehydrogenase complex, T-cell receptors from patients with primary biliary cirrhosis.

Progressive destruction of the intrahepatic bile ducts in patients with primary biliary cirrhosis (PBC) is thought to be mediated by cytotoxic T cells which recognize certain epitopes, such as the pyruvate dehydrogenase complex (PDC). To clarify the T-cell repertoire in PBC, we analyzed T-cell receptor (TCR) Vbeta-chain messages expressed in peripheral blood mononuclear cells (PBMCs) stimulated with PDC and in liver biopsy specimens. PBMCs from 12 PBC patients and 6 healthy controls were examined. The TCR Vbeta repertoires of unstimulated PBMCs and PBMCs stimulated with PDC purified from bovine heart were analyzed, using the reverse transcriptase-polymerase chain reaction (RT-PCR) and single-strand conformation polymorphism (SSCP). Liver biopsy specimens from 5 PBC patients were also analyzed. In the PBC patients, several different T-cell clones, some of which showed the same mobility, were evident in both the PDC-stimulated and unstimulated PBMCs, as demonstrated by SSCP analysis. In addition, TCR clonality of infiltrating lymphocytes in the liver was also observed in PBC patients, showing common clonal T-cell accumulation with that seen in PBMCs stimulated with PDC. These data indicate that common clonal T-cell accumulation specific for PDC may be present in both peripheral PBMCs and the liver of patients with PBC.

Case-Control Studies↗
PubMed1998

Detection of TNF alpha and Fas ligand mRNA within synovial mononuclear cells by fluorescence in-cell labeling PCR (FICL-PCR).

T cells that infiltrate the synovial lesions of rheumatoid arthritis may play a key role in its pathogenesis. To learn more about their functional nature, we determined the frequency of synovial T cells that harbored the TNF alpha and Fas ligand transcript by a technique, called Fluorescence In-Cell Labeling Polymerase Chain Reaction (FICL-PCR). The mRNA of interest was detected in fixed cells by the incorporation during PCR of a fluorescein-12-dUTP label following an initial reverse transcription PCR step. Using this technique the CD3 transcript was detected in the T leukemic cell line, MOLT-4, with calculated sensitivity and specificity values of 91% and 100%, respectively. The percentage mean (+/-S.D.) of TNF alpha mRNA positive cells and Fas ligand mRNA positive cells in peripheral blood mononuclear cells from 12 rheumatoid arthritis patients were 5.1+/-2.3% and 4.8+/-3.1%, respectively. The percentage mean (+/-S.D.) of TNF alpha mRNA positive cells and Fas ligand mRNA positive cells among synovial mononuclear cells from six rheumatoid arthritis patients was 16.8+/-8.3% and 10.8+/-1.8%, respectively. This result indicates that the cytotoxic T cells expressing TNF alpha accumulate in rheumatoid arthritic lesions where they may play a pathogenic role.

Arthritis, Rheumatoid↗
PubMed1998

Apoptosis-mediated regulation of recombinant human granulocyte colony-stimulating factor production by genetically engineered fibroblasts.

We investigated the feasibility of an inducible apoptosis system to regulate cells genetically engineered for ectopic cytokine production. In a previous study, cDNA encoding the ligand-binding domain of the rat estrogen receptor was fused to the sequence for murine Fas transmembrane and cytoplasmic regions, and expression of the fusion protein (MfasER) in L929 fibroblasts resulted in estrogen-dependent apoptosis. We applied this MfasER/estrogen strategy to apoptosis-mediated regulation of cytokine production, using the human granulocyte colony-stimulating factor (G-CSF) as a model. Upon estrogen treatment, the G-CSF producers expressing MfasER showed an apoptotic phenotype and died in several hours, with termination of G-CSF production. This estrogen-induced apoptosis was not influenced by whether the target cells were proliferating or resting, unlike a conventional suicide system involving the herpes simplex virus 1 thymidine kinase (HSVtk). That is, estrogen induced prompt and extensive apoptosis in the resting cells which expressed MfasER, while ganciclovir treatment induced only partial reduction of the resting cells which expressed HSVtk. These results imply the feasibility of apoptosis-mediated regulation of cytokine production by genetically modified cells for supplement gene therapy.

Animals↗
PubMed1998

A role for granulocyte and monocyte apheresis in the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory condition, the etiology of which is not well understood. Recent reports indicate a major role of granulocytes in the pathogenesis of RA; arthritic joints are infiltrated with phagocytic leukocytes, granulocytes, and monocytes/macrophages, and it is believed that these cells, by releasing degradative proteinases, cytokines, and reactive oxygen species, contribute to joint destruction. Hence, the apheresis of granulocytes and monocytes may benefit patients with RA. Granulocyte and monocyte apheresis was carried out in 143 patients with RA using an apheresis column (G-1) packed with 220 g cellulose acetate beads, which selectively adsorb granulocytes and monocytes. Patients received 1 or 2 apheresis sessions, each of 1 h duration per week over a 4 week period at a flow rate of 30 ml/min. Apheresis significantly reduced swollen and tender joint counts and the duration of morning stiffness, and it increased grip strength, together with suppression of tumor necrosis factor-alpha and interleukin-1beta production by peripheral blood monocytes. It is concluded that this alternative treatment induces a kind of immunomodulation.

Adult↗