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Biomedical subjects

H Shigematsu

Publications and source records attributed to H Shigematsu.

At least 109 records · Page 6Linked to original sources
PubMed1998

Contribution of mast cells to the tubulointerstitial lesions in IgA nephritis.

BACKGROUND: Mast cells have never been extensively investigated in renal disease, particularly glomerulonephritis. Recent improvements in monoclonal antibody production to mast cell specific enzymes have made it possible to study mast cells in tissues more accurately and easily. Mast cells have been found to secrete basic fibroblast growth factor (bFGF) in human pulmonary fibrosis. METHODS: Mast cells in 67 cases of IgA nephritis were investigated. Toluidine blue (TB) stainings at pH 5.0 and pH 0.5 were employed histochemically, and anti-human mast cell tryptase and chymase monoclonal antibodies were used immunohistochemically. Anti-bFGF antibody was also used immunohistochemically. RESULTS: Mast cells were scattered in the interstitium including in fibrotic areas. TB pH 0.5-positive mast cells were more numerous than TB pH 5. 0-positive mast cells. Immunostaining with anti-tryptase monoclonal antibody detected more mast cells than the TB stainings. Mast cells in the interstitium of IgA nephritis had both tryptase and chymase. Immunoelectron microscopy showed that tryptase was exclusively localized in the specific granules of mast cells. The average number of tryptase positive mast cell in the interstitium of IgA nephritis was lower than that of T lymphocyte but more than that of macrophages. The average number of mast cells increased with the progression of interstitial fibrosis and had a significant correlation with 24-hour creatinine clearance. Using double labeled immunohistochemistry, some tryptase-positive mast cells had bFGF in their cytoplasm. Electron microscopy showed that mast cells were associated with fibroblasts and/or lymphocytes in the interstitium. CONCLUSION: Mast cells are one of the constitutive cells in the interstitium of IgA nephritis patients and affect renal function by contributing to the interstitial fibrosis.

Adolescent↗
PubMed1998

Effect of interleukin 1 beta-induced fever on hepatic drug metabolism in rat.

1. A fever-induced model in rat was created by repeated injection of interleukin 1 beta (IL-1 beta) in the cerebroventricle and the influence of fever on hepatic drug metabolism was investigated. Fever apparently decreased the content of cytochrome P450 (CYP) and the activities of NADPH-ferrihaemoprotein reductase (fp2), aminopyrine N-demethylase, aniline hydroxylase, FAD-monooxygenase, p-nitrophenol UDP-glucuronosyl-transferase and glutathione S-transferase. Immunoblot analysis of the CYP isozymes indicated that CYP2C11 and CYP3A were extensively decreased in the IL-1 beta-induced fevered rat. 2. Repeated administration (5 days) of mefenamic acid in the fevered rat could not restore the activities of fp2, aminopyrine N-demethylase and aniline hydroxylase to control levels, although their hyperthermic state had been improved. The CYP content in the mefenamic acid-treated fevered rat was also lower than that in the control. 3. These findings suggest that fever impairs the hepatic drug-metabolizing capacity (both oxidation and some conjugations) and that the fever-induced impairments are partially retained, even if the hyperthermia has been offset by the administration of antipyretics.

Aminopyrine N-Demethylase↗
PubMed1998

Unilateral arterial reconstruction for aortoiliac occlusive disease.

METHODS: The outcomes of 234 arterial bypasses for aortoiliac occlusive disease were retrospectively analyzed. Surgical procedures included 60 bilateral aorto-/iliofemoral bypasses, 140 unilateral aorto-/iliofemoral bypasses, and 34 femorofemoral cross-over bypasses. Nineteen patients (13.6%) showed deterioration of the contralateral iliac artery after the initial unilateral operation. Of these patients, 11 patients underwent further surgical treatments; including 5 unilateral aortofemoral operation bypasses, 2 iliac thromboendarterectomies, 2 iliac PTA's, 1 femorofemoral bypass, and 1 bilateral aortofemoral bypass. The remaining 8 patients received conservative treatment because of their risk factors. The patency rate of the unilateral reconstruction has improved during the last 12 years according to our historical analysis. RESULTS: Our results demonstrate that unilateral vascular reconstruction is a valuable alternative to conventional bilateral reconstruction in unilateral symptomatic aortoiliac occlusive disease. CONCLUSIONS: Accurate preoperative diagnosis and early detection of the progression of sclerotic lesions on the contralateral side are the keys to successful results.

Aorta↗
PubMed1998

Risk factors for restenosis after balloon angioplasty in focal iliac stenosis.

BACKGROUND: The risk factors for restenosis after angioplasty have not yet been established because of the inconsistencies among treated lesions, differences in the techniques used, and variable end points. We evaluated the predictive variables relating to postangioplasty restenosis. METHODS: One hundred sixty-one transluminal balloon angioplasties were studied in 138 consecutive patients with focal iliac arterial stenosis (< or = 4 cm) caused by arteriosclerosis between January 1981 and December 1995. Restenosis was diagnosed on the basis of recurrent symptoms associated with an apparent drop in the ankle-brachial pressure index and angiographic visualization of restenosis. RESULTS: Being younger than 60 years (risk ratio 2.585) and poor runoff (risk ratio 2.328) were found to be important variables predicting restenosis by the Cox regression model. The restenosis-free patency rates were significantly better in patients older than 60 years of age (p = 0.0242), with good distal runoff (p = 0.0487), and without diabetes (p = 0.0111). CONCLUSIONS: Being younger than 60 years of age and poor distal runoff are important predictors of restenosis after iliac balloon angioplasty.

Adult↗
PubMed1998

Aneurysm induced by periarterial application of elastase heals spontaneously.

BACKGROUND: The pathogenesis of aortic aneurysms remains largely unknown, despite aneurysmal rupture being an increasingly common catastrophe. METHODS: This study was designed to elucidate the mechanism of arterial dilatation histologically and electron microscopically, utilising a new animal model. Elastase, 3.0 mg/ml, was applied to the abdominal aortae of 18 New Zealand white rabbits from the adventitia side for 3 hours. The rabbits were sacrificed at 0, 3, 14, 28, 42 and 90 days after the procedure (n=4, 3, 2, 2, 2, 3). RESULTS: Two rabbits were found to have developed aortic rupture. On day 0, elastase application induced fusiform aneurysms up to 1.62+/-0.14 times the pre-elastase application aortic diameter. Dilated walls revealed medial elastolysis, degeneration of smooth muscle cells (SMCs) and damaged endothelial cells. By day 3, the smooth muscle cells had changed to the synthetic type. Aneurysms did not progress, and after 42 days, showed gradual shrinkage. By day 90, aortic diameters had nearly normalised. CONCLUSIONS: Aortic walls also returned to the pre-elastase application thickness and some mature medial elastic lamellae showed regeneration. Medial smooth muscle cells reverted to the contractile type. Aortic dilatation induced by peri-aortic application of elastase heals spontaneously, accompanied by regeneration of smooth muscle cells. Irreversible degeneration of medial smooth muscle cells appears to be more critical to aneurysm formation than degeneration of elastic lamellae.

Animals↗
PubMed1998

Advantages of straight graft for abdominal aortic aneurysm repair.

The advantages of aneurysm repair with straight tube graft were studied. Between January 1984 and March 1994, 277 patients with abdominal aortic aneurysm underwent operation using straight or bifurcated prosthetic grafts. Of those 277 patients, 37 patients (14%) received straight grafts and the remaining 240 patients received bifurcated ones. These two patient groups were compared in terms of influences of intraoperative aortic clamping, operative time, postoperative recovering condition, incidence of perioperative complications, and long-term results. Hemodynamic influences of aortic clamping were determined by the changes in systemic blood pressure. The duration of aortic clamping was significantly longer in the bifurcated graft group than in the straight graft group (p < 0.01). In addition, the elevation of blood pressure was significantly higher after aortic clamping in the bifurcated graft group than in the straight graft group (p < 0.05) although the blood pressure changes after release of the clamp did not differ significantly. The bifurcated grafts required significantly longer operating time than the straight grafts. There was a tendency for the patients of bifurcated grafts to suffer from complications associated with long duration of the laparotomy, such as pneumonia and bowel obstruction. During an average follow-up period of 5 years, only one patient had to undergo subsequent operation for an aneurysm of the remaining iliac artery. This patient had had a dilatation of the hypogastric artery 1.5 times as large as is normal in the first operation. The long-term results of the remaining 36 patients with straight graft was satisfactory and the remaining iliac arteries were found to be intact. It is concluded that the surgical repair with straight tube graft is a durable procedure for patients with abdominal aortic aneurysms as long as the dilatation of the iliac artery is limited to 1.5 times the normal dilatation.

Aged↗
PubMed1998

[A case of video-assisted thoracic surgery for congenital esophago-bronchial fistula].

A 42-year-old male was admitted to our hospital because barium esophagograpm showed an esophago-bronchial fistula with an esophageal deverticulum. He has had frequent episodes of cough at drinking water since childhood. A chest CT scan showed mild inflammatory change and bronchiectasis in the right S6. Division of the fistula by video-assisted thoracoscopic surgery (VATS) was performed. There was no evidence of inflammation and adherent lymph nodes around the fistula. This case was diagnosed as a congenital esophago-bronchial fistula by operative findings and clinical course. The fistula was dissected easily and divided by an auto-suturing instrument. The affected lung could be preserved. The patient was discharged on the 10th postoperative day. VATS is an effective treatment for the patients of congenital esophago-bronchial fistula (Braimbrige type I and II), if they are not accompanied with pulmonary abscess or pleural empyema.

Adult↗
PubMed1997

Role of the vav proto-oncogene product (Vav) in erythropoietin-mediated cell proliferation and phosphatidylinositol 3-kinase activity.

The vav proto-oncogene product (Vav), which is specifically expressed in hematopoietic cells, contains multiple structural motifs commonly used by intracellular signaling molecules. Although a variety of stimuli including erythropoietin (Epo) have been shown to tyrosine phosphorylate Vav, little is known about the Vav signal transduction pathway. Here, we have investigated the role of Vav in the Epo signaling pathway by characterizing its interaction with other proteins, using the human Epo-responsive cell line, F-36P. Immunoprecipitation and immunoblot analyses have demonstrated that Vav was associated with the Epo receptor (EpoR) in an Epo-independent manner and was tyrosine-phosphorylated after Epo stimulation. Furthermore, two phosphotyrosine proteins (pp70 and pp100) co-immunoprecipitated with the regulatory subunit of phosphatidylinositol 3-kinase (PI3-kinase) (p85) were identified as EpoR and Vav, respectively. The interaction between Vav and p85 was shown to be mediated through the SH2 domains of p85 by an in vitro binding assay and confirmed by the presence of in vitro PI3-kinase activity associated with Vav. Treatment of the cells with antisense-vav and -p85 abrogated Epo-induced cell proliferation and PI3-kinase activity. Finally, we found that JAK2 was associated with Vav in vivo and that Vav could be tyrosine-phosphorylated by activated JAK2 in vitro. These results suggest the possible role of JAK2 for tyrosine phosphorylation of Vav and involvement of Vav and PI3-kinase in Epo-induced proliferative signals.

Cell Cycle Proteins↗
PubMed1997

Platelet endothelial cell adhesion molecule-1 is a major SH-PTP2 binding protein in vascular endothelial cells.

Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is rapidly tyrosine phosphorylated in mechanically stimulated vascular endothelial cells (ECs). A 65-kDa protein from ECs specifically bound to the c-Src phosphorylated PECAM-1 cytoplasmic domain and was identified as a protein tyrosine phosphatase SH-PTP2 (SHP2, Syp). PECAM-1 was coimmunoprecipitated by anti-SH-PTP2 from EC extracts as a major binding protein, and the level of association increased when PECAM-1 was tyrosine phosphorylated. This association was mediated by SH2 domains of SH-PTP2. A rapid translocation of SH-PTP2 into cell-cell adhesion sites, where PECAM-1 was localized, occurred in mechanically stimulated cells. Our results suggest that PECAM-1 is a component of a mechanosensing machinery acting upstream of SH-PTP2.

Animals↗
PubMed1997

Sarcomatoid renal cell carcinoma with widespread metastases to liver and bones in a kidney transplant recipient.

A case of sarcomatoid renal cell carcinoma with widespread metastases to liver and bones in a cadaver renal transplant recipient is reported in this article. The patient underwent a kidney transplant at the age of 43 and was treated with various immunosuppressive agents after surgery. Twelve months after the transplantation, multiple tumors were found in the liver, and the patient died 8 months later. Pathological examination at autopsy revealed renal cell carcinoma with a sarcomatoid component in the right native kidney and metastases to liver and bones. It is unusual for renal cell carcinoma to undergo sarcomatous transformation and to metastasize to the liver before reaching other organs. We speculate that immunosuppressants may have altered malignant cell proliferation, invasion, and the form of metastasis in this case.

Adult↗
PubMed1997

Results of arteriovenous fistula revision in the forearm.

PURPOSE: We assessed the usefulness of revision for hemodialysis arteriovenous fistulae. METHODS: From 1985 to 1994, 287 arteriovenous fistulae were created at our facility. "Primary" patency was defined as the duration of fistula patency without revision, and "secondary" patency was defined as the duration of fistula patency after successful revision in the forearm not requiring prosthesis. RESULTS: The secondary patency rate was significantly better than the primary patency rate (89% versus 41% at 5 years, P < 0.01). The secondary patency rate in diabetic patients did not differ from that in nondiabetics, although there was a significant difference in the primary patency rate between these two patient groups (diabetics 30% versus nondiabetics; 45% at 5 years, P < 0.01). CONCLUSIONS: Revision is a reliable procedure for salvaging a failed fistula, which yields an acceptable patency rate regardless of the patient's risk factors for arteriosclerosis.

Adult↗
PubMed1997

A new method for the assessment of venous insufficiency in primary varicose veins using near-infrared spectroscopy.

PURPOSE: Patients with chronic venous insufficiency (CVI) were evaluated from the aspect of ambulatory venous function using near-infrared spectroscopy (NIRS). METHODS: Seventy-two primary varicose veins of 59 patients (varicose group) and 20 normal limbs of 13 volunteers (normal group) were studied. The affected limbs of the patients were divided into three groups according to the classification advocated by an International Consensus Committee in 1995: mild CVI with class 2 or 3 (50 limbs); moderate CVI with class 4 (11 limbs); and severe CVI with class 5 or 6 (11 limbs). All of the patients underwent a treadmill walking test, during which NIRS was applied. Oxygenated hemoglobin (OxyHb) and deoxygenated hemoglobin (DeoHb) were continuously measured by NIRS during exercise. The ambulatory venous retention index (AVRI) obtained from serial changes in DeoHb was assessed comparatively in the four groups (normal and mild to severe CVI). In addition, 19 limbs in 13 patients were evaluated with air plethysmography for comparison with the data obtained by NIRS. RESULTS: Two distinct patterns of DeoHb change were observed. During exercise, the DeoHb level decreased in the normal group as a result of calf muscle contraction, whereas in the varicose group the DeoHb level rose because of an apparent venous reflux into the calf muscles. AVRI studies demonstrated a significant difference (p < 0.0001) among groups. Although there was no apparent relationship between AVRI and ejection fraction, AVRI showed a significant correlation with the venous filling index (r = 0.61) and a weak correlation with the residual volume fraction (r = 0.41). CONCLUSION: NIRS is useful for accurately assessing ambulatory venous dysfunction in patients with primary varicose veins.

Adult↗
PubMed1997

Anti-angiogenic drug AGM1470 suppresses smooth muscle cell migration induced by endothelial PDGF.

OBJECTIVES: To examine the effects of the anti-angiogenic drug AGM1470 on smooth muscle cell (SMC) migration activity stimulated by endothelial cell (EC)-derived mitogen. MATERIALS AND METHODS: Study 1; EC's were cultured under pulsatile flow using MCDB151 medium. From the supernatant of these EC dishes we devised two types of conditioned medium; anti-PDGF(+) containing 10 micrograms/ml anti-PDGF antibody, and anti-PDGF(-) containing no antibody. SMC's were cultured using both media. Study 2; EC's were cultured under the same conditions using both types of medium; MCDB151 medium containing 10 ng/ml AGM1470, and MCDB151 medium alone. After the AGM1470 concentration had been adjusted to 10 ng/ml, SMC's were cultured using each medium; AGM-exposed EC and AGM-non-exposed EC. SMC colony spreading distances were measured as an index of mitogenic activity for 4 days. RESULTS: Study 1; the anti-PDGF(-) group showed an apparently greater spreading distance than the anti-PDGF(+) group. Study 2; the AGM-non-exposed EC group showed a significantly greater spreading distance than the AGM-exposed EC group. However, MTT assay revealed no differences in proliferation between the two groups. CONCLUSION: AGM1470 suppresses the EC production of this PDGF-like mitogen as well as SMC migration activity.

Analysis of Variance↗
PubMed1997

Analysis of T-cell receptor beta of the T-cell clones reactive to the human PDC-E2 163-176 peptide in the context of HLA-DR53 in patients with primary biliary cirrhosis.

T-cell-mediated autoimmune mechanisms are considered to be involved in the pathogenesis of primary biliary cirrhosis (PBC). In the previous study, we identified the immunodominant T-cell epitope on the E2 component of pyruvate dehydrogenase complex (PDC-E2) in patients with PBC who have HLA-DRB4*0101. In this report, we revealed that the frequency of the T cells reactive to the human PDC-E2 163-176 peptide is significantly increased in the peripheral blood of patients with PBC as compared with healthy subjects. We also confirmed that these T cells were all restricted with HLA-DRB4*01 (DR53) by using HLA-DR-transfected L cells. These results together with the evidence that the immunodominant B-cell epitope overlaps with the human T-cell epitope of the PDC-E2 antigen indicate that the T cells reactive to this epitope are closely associated with the pathogenesis of PBC at least in patients who have HLA-DR53. Therefore, we analyzed the T-cell receptor (TCR) Vbeta sequence of the five different T-cell clones and the three T-cell clones derived from three patients with PBC and healthy subjects, respectively, which are reactive to the human PDC-E2 163-176 peptide in the context of HLA-DR53. The Vbeta- and the Jbeta-gene usages were diverse among the T-cell clones (Vbeta11-Jbeta1.4, Vbeta8-Jbeta1.2, Vbeta12-Jbeta2.1, Vbeta10-Jbeta1.5, and Vbeta20-Jbeta2.1) in patients with PBC. By contrast, in the third complementarity determining region (CDR3), G was frequently found and GXG or GXS motif was identified in all T-cell clones. Moreover, RGXG motif was found in three clones generated from two patients. In healthy subjects, the Vbeta- and the Jbeta-gene usages were also diverse, and GXG and RGXG motif were found. These results indicate that the T cells may recognize the ligand (the human PDC-E2 163-176 peptide/HLA-DR53 complex) using the limited motif in the CDR3 region and that the design of CDR3-specific immunotherapy would be possible using these motifs.

Amino Acid Sequence↗
PubMed1997

Production of a T-cell clone which reacts with membrane proteins of Acholeplasma laidlawii.

The role of cellular immunity in mycoplasma infection is not completely understood. In this study, we established mycoplasma-specific T-cell clones to evaluate cellular immunity in mycoplasma infection. We developed a T-cell clone (G-10) which was stimulated with Acholeplasma laidlawii. The T-cell clone G-10, CD4+ and T-cell receptor (TCR) alpha beta- recognized the 42- and 65-kilodalton (kDa) membrane proteins of A. laidlawii and responded to A. hippikon. Hence, the application of mycoplasma-specific T cells such as G-10 in animal models may allow the assessment of cellular immune response to mycoplasma infection.

Acholeplasma laidlawii↗
PubMed1997

Histological grading and staging of IgA nephropathy.

More than 25 years have passed since immunoglobulin A (IgA) nephropathy was introduced as a disease entity independent of glomerulonephritis. It has been known that more than 30% of cases have gone into end-stage renal failure within 20 years, indicating the presence of a chronic active group in this disease. Histologically this disesase is composed of at least three types of tissue damage: (i) minimal inflammation including deposition of IgA-containing substances with minor matricial increase; (ii) acute lesions characterized by matricial damage of glomerular basement membrane (membranolysis) and/or mesangial matrix (mesangiolysis) with inflammatory cell accumulation and/or intrinsic cell proliferation; and (iii) chronic lesions mainly composed of postinflammatory sclerosis. The progression is actually accelerated by the frequency of acute lesions, resulting in increased glomerular sclerosis foci. In such a situation, the histologic grading and staging (G-S) system is proposed, with the aim of having a more precise understanding of the disease process. The histological grade (G) is estimated by the extent of acute glomerular and tubulointerstitial lesions, and the stage (S) is evaluated by the increase of extracellular matrices of the glomeruli and interstitial fibrosis. The evaluation of G and S is expressed semiquantitatively for more helpful clinical use.

Acute Disease↗