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Biomedical subjects

Satoshi Ito

Publications and source records attributed to Satoshi Ito.

At least 37 records · Page 2Linked to original sources
PubMed2005

Perfusion through the dorsalis pedis artery for acute limb ischemia secondary to an occlusive arterial cannula during percutaneous cardiopulmonary support.

Percutaneous cardiopulmonary support (PCPS) is a powerful resuscitation tool for patients in cardiogenic shock. The femoral artery is generally used for arterial access; however, vascular complications, particularly in atherosclerotic arteries, can occur. Although such complications occur infrequently, they can be fatal. We describe the case of a 75-year-old woman who required extended PCPS for cardiogenic shock secondary to coronary spasm after on-pump beating coronary artery bypass grafting. Limb ischemia occurred because of an occlusive cannula, and distal perfusion with a 20G elastic intravenous catheter inserted into the dorsalis pedis artery resolved the ischemia. The catheter was connected to the side port of an oxygenator and provided distal limb perfusion during PCPS. This technique appears to be useful in treating limb ischemia and may have application in patients with arterial occlusive disease who are dependent on mechanical support.

Acute Disease↗
PubMed2005

Clinical characteristics of anti-glucose-6-phosphate isomerase antibody-positive Japanese patients with rheumatoid arthritis.

Anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) are known to be arthritogenic in mice. These Abs are elevated in several forms of arthritic condition in humans, although their prevalence in rheumatoid arthritis (RA) patients is still in debate. Some RA patients have increased levels of anti-GPI Abs, but their clinical manifestation and relevance to other Abs are not clearly elucidated. The aims of this study were to explore the clinical and hematological characteristics of RA with anti-GPI Abs, and to compare their prevalence in RA patients, systemic lupus erythematosus (SLE) patients, and healthy subjects (HS) in a Japanese population. Anti-GPI Abs were positive in 16 patients with RA (12%, n = 137), in 10 patients with SLE (8%, n = 131), and in 6 HS (4%, n = 139). C-reactive protein (CRP), immunoglobulin G, and the antinuclear antibody titer were higher in anti-GPI-positive patients than in those who were negative (P = 0.049, P = 0.0003, and P = 0.002, respectively). Moreover, the positivity of anti-GPI Abs was correlated with CRP more than with rheumatoid factor in RA patients. It is unclear whether anti-GPI Abs can predict the progress of disease, but the prevalence of these Abs was higher in active RA patients with severe arthritis, suggesting that anti-GPI Abs may be related to the pathogenesis of severe forms of arthritis.

Journal Article↗
PubMed2005

Identification of three novel peptides that inhibit CD40-CD154 interaction.

The CD40-CD154 interaction is an attractive target for therapeutic intervention in various autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus (SLE), multiple sclerosis, and myasthenia gravis. In this study, to develop a new disruption strategy of the CD40-CD154 interaction, we screened for peptides with inhibitory effects on such ligation. 2 x 10(11) phage display libraries displaying liner peptides of 12-mer amino acids were screened by CD40-Ig binding assay and eight phages which expressed a different respective peptide (40BP-1 to -8) were able to specifically bind to CD40. Competitive inhibition analyses showed that 3 of the 8 peptides (40BP-N1-1 - APELPNMTPSWT; 40BP-N1-2 - APRPHTSYSPLP; and 40BP-N1-3 - GMTAPPPPRLTQ) blocked CD40-CD154 interaction when used at high concentrations. A consensus sequence (APxPPxxT) was conserved in these three peptides. These peptides may constitute a useful and novel strategy for the inhibition of the interaction between CD40 and CD154 molecules.

Journal Article↗
PubMed2005

Immunoglobulin G from anti-glucose-6-phosphate isomerase antibodies positive patient with rheumatoid arthritis induces synovitis in cynomolgus monkeys.

Anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) solely induce arthritis in mice. High titers of anti-GPI Abs are found in some patients with rheumatoid arthritis (RA), but their pathogenic role remains elusive. The aim of this study was to evaluate the pathogenic role of anti-GPI Abs in cynomolgus monkeys. IgG fractions were separated from sera of anti-GPI Abs-positive RA patients and healthy subjects and directly injected into the metacarpophalangeal joints of 4 cynomolgus monkeys. At day 16, the joints were harvested and examined histologically and immunohistochemically. The expression of C5a receptor (C5aR) molecule in the synovium was quantified by real-time PCR using cDNA from monkey joints. In monkey joints, IgG including anti-GPI Abs resulted in recruitment of granulocytes and mononuclear cells, strong deposition of human IgG on the articular surface, and overexpression of C5aR, but no joint swelling. No infiltrated cells or IgG deposition were observed in monkeys injected with IgGs from healthy subjects. Our results suggest that IgG fraction from RA patients including anti-GPI Abs may play a crucial role in the generation of synovitis in monkeys, although the pathogenesis of anti-GPI Abs in RA patients is still uncertain.

Animals↗
PubMed2005

Synthetic double-stranded RNA poly(I:C) combined with mucosal vaccine protects against influenza virus infection.

The mucosal adjuvant effect of synthetic double-stranded RNA polyriboinosinic polyribocytidylic acid [poly(I:C)] against influenza virus was examined under intranasal coadministration with inactivated hemagglutinin (HA) vaccine in BALB/c mice and was shown to have a protective effect against both nasal-restricted infection and lethal lung infection. Intranasal administration of vaccine from PR8 (H1N1) with poly(I:C) induced a high anti-HA immunoglobulin A (IgA) response in the nasal wash and IgG antibody response in the serum, while vaccination without poly(I:C) induced little response. Intracerebral injection confirmed the safety of poly(I:C). In addition, we demonstrated that administration of poly(I:C) with either A/Beijing (H1N1) or A/Yamagata (H1N1) vaccine conferred complete protection against PR8 challenge in this mouse nasal infection model, suggesting that poly(I:C) possessed cross-protection ability against variant viruses. To investigate the mechanism of the protective effect of poly(I:C), mRNA levels of Toll-like receptors and cytokines were examined in the nasal-associated lymphoid tissue after vaccination or virus challenge. Intranasal administration of HA vaccine with poly(I:C) up-regulated expression of Toll-like receptor 3 and alpha/beta interferons as well as Th1- and Th2-related cytokines. We propose that poly(I:C) is a new effective intranasal adjuvant for influenza virus vaccine.

Administration, Intranasal↗
PubMed2005

Two cases of systemic lupus erythematosus complicated with colonic ulcers.

We report two cases of systemic lupus erythematosus (SLE) complicated with colonic ulcerations. One patient was successfully cured by steroid therapy, while the other did not respond to steroid but oral mesalazine was effective. Systemic lupus erythematosus is frequently accompanied by gastrointestinal symptoms, but colonic lesions are quite rare, and the regular treatment is not fixed yet. The high-dose steroidal regimen may be effective for microvasculitis, although it may increase the risk of perforated ulcer of the intestinal tract, which is a life-threatening complication. Further analysis of its outcomes, and establishment of the regular guideline for its treatment are expected.

Adult↗
PubMed2005

Analysis of abnormally expressed genes in synovium from patients with rheumatoid arthritis using a column gel electrophoresis-coupled subtractive hybridization technique.

Rheumatoid arthritis (RA) is a chronic disease of unknown pathogenesis. To identify abnormally expressed genes in synovium from RA patients, we performed column gel electrophoresis-coupled subtractive hybridization (CGESH). CGESH is a newly developed subtractive hybridization technique to achieve sufficient enrichment of DNA sequences. CGESH was performed using restricted enzyme digested cDNA synthesized from mRNA of synovial tissues from one RA patient and one osteoarthritis (OA) patient. The obtained subtraction libraries (RA-OA) were screened by dot blot hybridization. The clones showing higher hybridization with the RA-OA probe were identified by sequence analysis and homology search. Their DNA sequencing revealed that the genes of HLA-DRB1, sequestosome 1, elongation factor 1alpha were included. Furthermore, a functionally unknown gene (FLJ00133) was also identified. It is reported that sequestosome 1 is a scaffold in the signal transduction of TNFalpha and interleukin 1, which are the important cytokines involved in the pathogenesis of RA. It is possible that other genes identified by the CGESH technique would be associated with the pathogenesis of RA, although there is no direct evidence yet. Our results imply that the CGESH technique is a useful tool to detect genes involved in the pathogenesis of RA. Further investigation of the functional roles of candidate genes should shed light on the pathogenesis of RA.

Arthritis, Rheumatoid↗
PubMed2005

Relationship between hormonal receptors, HER-2, p53 protein, Bcl-2, and MIB-1 status and the antitumor effects of neoadjuvant anthracycline-based chemotherapy in invasive breast cancer patients.

PURPOSE: The purpose of this study was to evaluate the predictive value of six different biological factors for neoadjuvant chemotherapy (NAC) in breast conservation treatment (BCT) for invasive breast cancer. MATERIALS AND METHODS: Thirty invasive breast cancer patients (31 breasts) who received NAC as BCT and needle biopsy before chemotherapy were included in this study. Breast cancer tissue was obtained with an 18G core needle with ultrasound guidance. Patients received two to five courses of CAF (cyclophosphamide 600 mg/m(2), pirarubicin 20-40 mg, 5-fluorouracil 600 mg/m(2)). Tissue sections from formalin-fixed paraffin-embedded blocks were stained for the presence of estrogen receptor (ER), progesterone receptor (PgR), HER (human epidermal growth factor receptor)-2, p53 protein, Bcl-2, and MIB-1 (Ki-67). Tumor reduction rate was assessed by MRI before and after chemotherapy. RESULTS: The tumor reduction rate did not differ according to the number of courses of chemotherapy administered. In both the univariate and multivariate analyses, HER-2-negative status was the only significant predictive factor of response (P<0.05). There was no correlation between response and hormone receptors, MIB-1, p53 protein, or Bcl-2 expression. CONCLUSION: This study suggests that breast cancer cells that overexpress HER-2 may be resistant to low-doses of anthracycline-based chemotherapy.

Adult↗
PubMed2005

The exploration of joint-specific immunoreactions on immunoglobulins G of anti-glucose-6-phosphate isomerase antibody-positive patients with rheumatoid arthritis.

The pathogenic role of autoantibodies in rheumatoid arthritis (RA) remains elusive. Anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) are candidates for arthritogenic Abs because they directly induce arthritis in mice. High titers of anti-GPI Abs are found in some RA patients with severe forms. The aim of this study was to analyze the role of IgG, including anti-GPI Abs, in the joints of RA patients. Synovial tissue was obtained from 6 patients with RA (3 anti-GPI Abs- positive and 3 anti-GPI Abs- negative) and compared histologically and immunohistochemically for IgG and C3 deposition. IgG fractions were separated from the sera of anti-GPI Abs-positive RA patients and healthy subjects, and injected into the metacarpophalangeal joints of 4 cynomolgus monkeys. On day 16, the joints were harvested and examined histologically and immunohistochemically. The expression of the C5a receptor (C5aR) molecule in the synovium was quantified by real-time PCR using cDNA from the monkeys' joints. The synovia of anti-GPI Abs-positive RA patients showed diffuse infiltration of cells, including mast cells, and strong deposition of IgG and C3. In monkeys, IgG from RA patients, including anti-GPI Abs, resulted in recruitment of granulocytes and mononuclear cells, strong deposition of IgG on the articular surface, and overexpression of C5aR, but no joint swelling. No infiltrated cells or IgG deposition were observed in monkeys injected with IgGs from healthy subjects. Our results suggest that IgG fraction from RA patients, including that of anti-GPI Abs, may play a role in the synovitis of RA, although the pathogenesis of human anti-GPI Abs is still uncertain.

Animals↗
PubMed2004

Glucose-6-phosphate isomerase variants play a key role in the generation of anti-GPI antibodies: possible mechanism of autoantibody production.

Glucose-6-phosphate isomerase (GPI), recognized as an autoantigen in the K/BxN arthritis model, is a ubiquitous cytoplasmic enzyme. Anti-GPI antibodies (Abs) are also detected in the serum of patients with arthritic diseases including rheumatoid arthritis (RA). So far, 24 GPI variants have been reported and most of these variants relate to non-spherocytic hemolytic disease. To understand the mechanisms of anti-GPI Ab production, cDNAs from peripheral blood mononuclear cells of subjects with or without anti-GPI Abs were cloned and sequenced. We identified 39 new GPI variants (57-1596 bp). The frequency of GPI variants in healthy control subjects (HS) with anti-GPI Abs (27/73, 31.5%) was significantly higher than that in anti-GPI Ab-negative HS (5/78, 6.4%, p < 0.001). The frequency of GPI variants in anti-GPI Ab-positive RA patients (22/77, 28.6%) was more significantly higher than in anti-GPI Ab-negative patients (1/63, 1.6%, p < 0.0001). Our results suggest that GPI variants may play a crucial role in the production of autoantibodies against ubiquitous GPI autoantigens.

Arthritis, Rheumatoid↗
PubMed2004

Dehydroepiandrosterone decreases elevated hepatic glucose production in C57BL/KsJ-db/db mice.

Dehydroepiandrosterone (DHEA) is known to improve hyperglycemia in diabetic db/db mice that are obese and insulin resistant. In a previous study, we reported that DHEA suppresses the elevated hepatic gluconeogenic glucose-6-phosphatase (G6Pase) activity and gene expression in C57BL/KsJ-db/db mice. In the present study, we evaluated the total amount of gluconeogenesis using NaH[(14)C]CO(3) and hepatic glucose production using fructose as a substrate in primary cultured hepatocytes. Despite hyperinsulinemia, the glucose production of db/db mice in the total body and hepatocytes was elevated as compared to their heterozygote littermate C57BL/KsJ-db/+m mice. Administration of DHEA significantly decreased the blood glucose level and increased the plasma insulin level in db/db mice. Administration of DHEA decreased the elevated total body and hepatic glucose production in db/db mice. In addition, the glucose production in the primary cultured hepatocytes of db/db mice was decreased significantly by the direct addition of DHEA or DHEA-S to the medium. These results suggest that administration of DHEA suppresses the elevated total body and hepatic glucose production in db/db mice, and this effect on the liver is considered to result from increased plasma insulin and DHEA or DHEA-S itself.

Adjuvants, Immunologic↗
PubMed2004

Mixed connective tissue disease associated with antineutrophil cytoplasmic antibodies against proteinase-3 and systemic atherosclerosis: a case report.

A 47-year-old woman presented with facial spasm, swollen fingers and Raynaud's phenomenon due to cerebrovascular disorder and mixed connective tissue disease (MCTD). Although she was positive for both antineutrophil cytoplasmic antibodies against proteinase-3 (PR3-ANCA) and anti-U1 RNP antibodies, she did not meet the American College of Rheumatology classification criteria for Wegener's granulomatosis (WG). Physical and histopathological examinations revealed severe systemic atherosclerosis without any of the traditional risk factors. Elevated levels of malondialdehyde-modified LDL and antioxidized LDL autoantibodies, which are considered to be key factors in the pathogenesis of atherosclerosis, were also detected in the serum of this patient. In this case, systemic atherosclerosis might have been linked to these autoimmune reactions.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2004

A case of Takayasu arteritis complicated with glomerulonephropathy mimicking membranoproliferative glomerulonephritis.

We report on a 65-year-old Japanese woman with Takayasu arteritis who developed severe proteinuria, hypertension, and renal dysfunction. Renal angiography demonstrated moderate irregular narrowing of both renal arteries. Renal biopsy showed glomerulonephropathy mimicking membranoproliferative glomerulonephritis (MPGN) with glomerular capillary wall thickening ("double contour") accompanied by mesangial cell proliferation and moderate increase of mesangial matrix without deposits of C3. Electron microscopy showed no subendothelial deposit and no circumferential mesangial interposition (CMI), and these findings are different from MPGN. In this report we present a case of Takayasu arteritis associated with glomerulonephropathy mimicking MPGN.

Aged↗
PubMed2004

A case of pneumatosis cystoides intestinalis in a patient with polymyositis and interstitial pneumonia.

We report the case of a 49-year-old man who presented with pneumatosis cystoides intestinalis associated with polymyositis and interstitial pneumonia. Three months after the administration of prednisolone and cyclosporine, he noticed mild abdominal distension, and a radiographic examination showed intraperitoneal free gas and intramural gas, suggestive of pneumatosis cystoides intestinalis (PCI). Additional treatment with a combination of doxycycline and high-dose oxygen therapy was effective in relieving the clinical symptoms and reducing the intramural gas.

Journal Article↗
PubMed2004

Tritium in [18O]water containing [18F]fluoride for [18F]FDG synthesis.

The presence of tritium in enriched [18O]water irradiated with 9.6 MeV protons used to produce [18F]fluoride by the 18O(p, n)18F reaction was inferred from the cross sections and threshold energies of the 18O(p, t)16O reaction, and the existence of tritium was confirmed experimentally. Tritium was also detected in both [18O]water recovered for recycling and waste acetonitrile solutions. The purified [18F]FDG was not contaminated with 3H. The amount of 3H discharged into the air was far less than the International Basic Safety Standard Level.

Drug Contamination↗
PubMed2004

Increase in the ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 in saliva from patients with primary Sjögren's syndrome.

BACKGROUND: To investigate the ratio of matrix metalloproteinase (MMP) to tissue inhibitor of metalloproteinase (TIMP) in primary Sjögren's syndrome (PSS), patients and healthy subjects MMP-2, 9 and TIMP-1, 2 levels were measured in saliva. METHODS: Stimulated whole-mixed saliva was collected from 32 patients and 26 healthy subjects. MMP-2, 9 and TIMP-1, 2 levels were measured using enzyme-linked immunosorbent assay (ELISA) and the sandwich enzyme immunoassay (sandwich EIA). Zymography and reverse zymography were used to identify MMPs and TIMPs. RESULTS: MMP-9 (gelatinase-B) level in saliva was significantly increased in the patients. MMP-9 (ng/ml): patients 231.02 +/- 151.77 (mean +/- S.D.), healthy subjects 145.87 +/- 111.65 (p < 0.05). MMP-2 levels were not detected with this system kit in either healthy subjects or patients. The differences in TIMPs were only trends and not statistically significant (p > 0.05). Accordingly, MMP-9/TIMP-1 was greatly increased in the patients (2.60 +/- 1.18) than in the healthy subjects (1.28 +/- 1.11) (p < 0.01). CONCLUSION: This study found that MMP-9/TIMP-1 and MMP-9 levels in the saliva were significantly higher in pSS patients than those in healthy subjects. Our results indicate that the increase in MMP-9/TIMP-1, rather than the increase in MMP-9, in pSS patients' saliva is strongly involved in destruction of glandular and salivary duct tissues.

Enzyme-Linked Immunosorbent Assay↗
PubMed2004

Renal outcome and predictors of clinical renal involvement in patients with silent lupus nephritis.

OBJECTIVES: We investigated the development of clinically overt nephritis in patients with silent lupus nephritis in an effort to determine predictors of onset. METHODS: We selected 31 patients with systemic lupus erythematosus (SLE) who were diagnosed as having silent lupus nephritis between 1985 and 1995. Urinalysis, blood cell count, serum creatinine, complement levels, and anti-double-stranded DNA antibody (anti-dsDNA antibody) levels were followed retrospectively for at least 60 months in each patient. RESULTS: During the follow-up period, 8 patients developed clinical renal disease and 23 had no renal impairment. The mean time of overt nephritis onset was 58 months and renal function deteriorated mildly in 3 patients. Although clinical and laboratory findings were not significantly different at SLE onset, patients with overt nephritis showed both persistent elevation of anti-dsDNA antibodies and persistently low levels of serum C3 and CH50 for at least 24 months before the onset of overt nephritis. CONCLUSIONS: Although the renal prognosis was relatively favorable, 25.8% of patients developed overt nephritis during the follow-up period. Elevation of anti-dsDNA antibodies with hypocomplementemia was persisted in these patients, suggesting the utility of these factors as predictors of clinical renal involvement in silent lupus nephritis.

Adolescent↗