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Biomedical subjects

S Matsui

Publications and source records attributed to S Matsui.

At least 145 records · Page 8Linked to original sources
PubMed1996

Airway epithelial cells produce stem cell factor.

Airway epithelial cells modulate the inflammatory response in asthmatic, allergic and fibrotic lung diseases through the secretion of cytokines that regulate the movement and activation of inflammatory cells. Mast cells play an important role in the pathogenesis of these lung diseases. In this study we report that normal airway epithelial cells express stem cell factor which is a critical mediator of mast cell growth and differentiation and that transforming growth factor-beta inhibits secretion of stem cell factor by airway epithelial cells.

Bronchi↗
PubMed1996

Decreased E-cadherin expression is associated with haematogenous recurrence and poor prognosis in patients with squamous cell carcinoma of the oesophagus.

Reduced expression of E-cadherin is associated with tumour invasiveness and metastasis. To elucidate whether E-cadherin expression correlates with clinical outcome in patients with oesophageal cancer, 62 patients were investigated immunohistochemically using an anti-E-cadherin monoclonal antibody (HECD-1). Eight patients had normal levels of expression in the tumour, 25 had tumours that expressed high levels (50 per cent or more tumour cells staining positive for E-cadherin) and 29 had tumours expressing low levels (less than 50 per cent of cells expressing E-cadherin). Patients with normally expressing tumours had a better prognosis at 3 years than those with low-expressing tumours (P < 0.05). Postoperative death was correlated significantly with lymphatic invasion, lymph node metastasis, E-cadherin expression and depth of invasion (P < 0.05). Furthermore, haematogenous recurrence was correlated with E-cadherin expression (rs = 0.38, P < 0.01) and blood vessel invasion (rs = 0.28, P < 0.05). These results suggest that evaluation of E-cadherin immunoreactivity may predict haematogenous recurrence and poor prognosis in patients with oesophageal cancer.

Adult↗
PubMed1996

Immunomodulation by an adenylate cyclase activator, NKH477, in vivo and vitro.

Cyclic adenosine monophosphate (cAMP) is an intracellular second messenger which modulates T cell function. NKH477 is a direct adenylate cyclase activator derived from forskolin and now under clinical investigation as a positive inotropic agent. While the immunosuppressive effects of forskolin on lymphocytes have been reported, little is known about its effects in vivo. In this study, we investigated whether NKH477 has immunosuppressive effects in mice, namely on cardiac allograft survival, and on the generation of cytotoxic T lymphocytes (CTL), T cell proliferation in mixed lymphocyte reaction (MLR), and production of interleukin-2 (IL-2) in MLR and in mitogen response. We assessed the effects of standard immunosuppressant cyclosporin A (CsA) on IL-2 production and on allograft survival to estimate the intensity of rejection in this acute rejection model. Saline-treated C57BL/6 (H-2b) mice rejected DBA/2 (H-2d) cardiac allografts with a median graft survival time of 10 days. In contrast, median graft survival was prolonged to 12 and 15 days in mice treated with NKH477 at 1 and 3 mg/kg/day, respectively (P < 0.01 vs control). The equivalent dose of CsA (40 mg/kg/day) to the maintenance dose after clinical cardiac transplantation prolonged median graft survival time to 15.5 days, indicating that high dose of NKH477 was as efficacious as lower dose of CsA. Addition of NKH477 to the culture medium suppressed the generation of CTL, T cell proliferation in MLR, and production of IL-2 in MLR and in mitogen response. These results suggest that NKH477 exerts a beneficial effect on murine cardiac allograft survival by modulating T cell function.

Acute Disease↗
PubMed1996

Preparation of an activity-inhibiting monoclonal antibody against human placental aromatase cytochrome P450.

We produced a murine monoclonal antibody (MAb) to human placental aromatase cytochrome P450. This MAb, designated MAb3-2C2, was selected on its ability to suppress aromatase activity. The specificity of this MAb was assessed by selective immunoprecipitation of 125I-labeled aromatase cytochrome P450 as well as by the identification of a 55-kDa protein, which was enriched and purified by immunoaffinity chromatography on a MAb-coupled Sepharose 4B column. The MAb was able to suppress both human placental and ovarian microsomal aromatase. Species differences of aromatase were recognized by MAb3-2C2 on the basis of differential immunosuppression of aromatase activity. The antibody had no effect on non-aromatase cytochrome P450s. MAb3-2C2 gave negative results with human placental aromatase P450 in the Western blot analysis. The data presented indicate that MAb3-2C2 is specific for aromatase cytochrome P450 and that its epitope is located in a fragile tertiary conformation of the enzyme, thus making it capable of sensitively affecting catalysis.

Animals↗
PubMed1996

Characteristic distribution of circulating autoantibodies against G-protein coupled cardiovascular receptors in patients with idiopathic dilated and hypertrophic cardiomyopathy.

Circulating autoantibodies against cardiovascular membrane receptors have been repeatedly demonstrated in a subgroup of sera of patients with idiopathic dilated cardiomyopathy. This short review summarizes the clinical findings on anti-receptor autoantibodies in patients with dilated cardiomyopathy.

Autoantibodies↗
PubMed1996

Immunomodulation: a new horizon for medical treatment of heart failure.

Recently, the intriguing possibility has been raised that heart failure may be mediated by the biological effects of cytokines. Indeed, we found elevation of plasma concentrations of various cytokines in patients with myocardial disease. We also detected positive tumor necrosis factor (TNF-alpha) immunoreactivity in right atrial tissues obtained during surgery from patients with severe heart failure. Therefore, we postulated that some aspects of heart failure may be related to non-lethal down-modulation of cardiac function by immune cells and their cytokines. Testing this hypothesis in an experimental model of murine myocarditis, we found that injection of recombinant human TNF-alpha increased mortality of the animals infected with myocarditis virus. The anti-TNF-alpha monoclonal antibody improved survival and attenuated the myocardial lesions. Whereas, administration of recombinant human IL-2 in the acute viremic stage increased survival rate, and resulted in less intense pathological changes in the myocardium while in the subacute aviremic stage, the same amount of IL-2 reduced survival rate and exacerbated severity of the disease. Therefore, cytokine release may initiate a beneficial inflammatory and immune response in the acute phase of the disease process, but the continued induction of cytokines and the enhanced natural killer (NK) cell activity in the later stage are no longer protective. Vesnarinone, a recently synthesized inotropic agent which has proved to benefit patients with congestive heart failure by improving prognosis, also increased the survival of individual subjects in the above-mentioned murine model of heart failure. Cytotoxicity of NK cells obtained from the virus infected animals was substantially reduced when treated with vesnarinone. Vesnarinone also inhibited production of TNF-alpha and other cytokines from stimulated human lymphocytes and cultured murine splenocytes. We conclude, therefore, that inhibition of NK cell activity and suppression of cytokine production appear to be important immunological defense mechanisms which could contribute to the observed salutary effects of vesnarinone in the treatment of chronic heart failure. More broadly, immunomodulation could pave the way for a new frontier in the management of heart failure.

Adjuvants, Immunologic↗
PubMed1996

Tetrahydrobiopterin biosynthesis enhanced by lipopolysaccharide stimulation in murine neuroblastoma cell line N1E-115.

We investigated for the first time the effect of lipopolysaccharide and the signal transduction pathway on the biosynthesis of tetrahydrobiopterin [(6R-L-erythro-1',2'-dihydroxypropyl) -2-amino-4-hydroxy-5,6,7,8-tetrahydropteridine], the cofactor for the enzymatic hydroxylation of the aromatic amino acids, in the murine neuroblastoma cell line N1E-115, which synthesizes tetrahydrobiopterin constitutively. Activation of N1E-115 cells with 1 microgram/ml lipopolysaccharide resulted in statistically significant increases in both intracellular tetrahydrobiopterin contents and the activity (Vmax) of GTP cyclohydrolase I, a rate-limiting enzyme in tetrahydrobiopterin de novo biosynthesis. Following simultaneous addition of the inhibitors of protein tyrosine kinases and GTP-binding proteins into serum-free culture media with lipopolysaccharide, we analyzed the transduction pathway of lipopolysaccharide signal toward the tetrahydrobiopterin biosynthetic system in N1E-115 cells. Our data indicate the following conclusions: (a) Protein tyrosine kinase systems are involved in mediating lipopoly-saccharide signal to tetrahydrobiopterin production, and (b) there may be a cross-talk between GTP-binding protein and the protein tyrosine kinase system in mediating lipopolysaccharide signal. These observations suggest that a neuronal cell such as N1E-115, which barely expresses CD14 on its cell surface, responds to lipopolysaccharide like macrophages and monocytes in the absence of soluble CD14.

Animals↗
PubMed1996

Primary human fibroblasts induce diverse tumor invasiveness: involvement of HGF as an important paracrine factor.

Fibroblasts have been considered to play an important role in tumor progression. In order to evaluate the contribution of fibroblasts to tumor invasion, TE2-NS, an esophageal cancer cell line, was cultured on collagen gel containing primary fibroblasts derived from normal esophageal submucosa or cancerous tissues of seven esophageal cancer patients. TE2-NS showed diverse invasiveness into the underlying gel containing fibroblasts, but did not invade the gel not containing fibroblasts. The invasiveness of TE2-NS, which expressed hepatocyte growth factor (HGF) receptor, was well-correlated with the concentration of HGF in conditioned medium. Administration of neutralizing antibody against HGF effectively suppressed the invasion, but application of recombinant HGF without fibroblasts induced little invasion into the gel. Fibroblasts from non-cancerous tissue generally secreted a larger amount of HGF and induced tumor invasion to a greater extent than those from cancer tissue, with large diversity. Interestingly, HGF secretion of fibroblasts from non-cancerous tissue was stimulated by co-culture with TE2-NS in two lines, but not in the other four. These results indicate that HGF is an important paracrine factor which induces tumor cell invasion, and the diversity of HGF production by fibroblasts might suggest different potentiality to induce tumor invasion among patients.

Cadherins↗
PubMed1996

Characteristic immunological tolerance in intrahepatic lymphocytes induced by bacterial superantigen SEB.

We have reported that the liver is closely associated with the hematolymphoid system and that the liver, as a lymphoid organ, may play an important role in the differentiation of lymphocytes and oral tolerance. To investigate the relevance of the liver to immunological tolerance, we compared the response pattern to Staphylococcus enterotoxin B (SEB) in intrahepatic lymphocytes (IHL) with those of spleen cells (SPC) and mesenteric lymph node cells (mLNC) during tolerance induction. Tolerance was induced by i.v. injections of SEB in all three organs. IHL had a distinct pattern from the other cells in the induction of unresponsiveness to SEB. While SPC and mLNC have a proliferation phase before the reduction of DNA synthesis, IHL become tolerant immediately without this phase. When IHL became tolerant in the early period after SEB injection, their nylon-wool column non-adherent (NW-NA) IHL were not recovered from unresponsiveness in vitro in spite of the addition of irradiated normal SPC as accessory cells. NW-NA IHL did not secrete IL-2 during this process, indicating that NW-NA IHL were in a state of functional anergy soon after the i.v. administration of SEB. Phenotypic analysis revealed that the characteristic changes of IHL during the induction of unresponsiveness might be associated with the kinetic modulation of CD4+ V beta 8+ T cells. These results suggest that the liver may hold a different mechanism for the induction of tolerance to SEB from that of SPC and mLNC.

Animals↗
PubMed1996

[Stage IIIa endometrial carcinoma: MR findings].

[PURPOSE]: An attempt was made to evaluate the ability of magnetic resonance (MR) imaging to diagnose stage IIIa endometrial carcinoma. [MATERIALS AND METHODS]: Thirty-three patients with endometrial carcinoma underwent MR imaging and surgery. Surgical staging was classified as I in 21 patients, II in 3 patients and III in 9 patients. The MR images of each patient were retrospectively reviewed by three radiologists. Only the clinical diagnosis of endometrial carcinoma was previously notified. Segmental disruption of the full thickness of the myometrium was considered serosal invasion. Intraperitoneal metastasis was diagnosed according to three criteria (intraperitoneal solid mass of isointensity compared with endometrial lesion, cystic mass excluding benign ovarian cysts, ascites). These evaluations were compared with the surgical findings and analyzed by the kappa statistic. [RESULTS]: The rates of sensitivity and positive predictive value (PPV) for serosal invasion were 33% and 6%, respectively. False positive evaluation frequently occurred when thickness of the intact myometrium was less than 5mm. The rates of sensitivity and PPV for intraperitoneal metastasis were 86% and 72%, respectively. The reason for false negative evaluation was small foci of intraperitoneal metastasis. Overall, sensitivity and PPV for stage IIIa were 86% and 69%, respectively. [CONCLUSION]: MRI was useful in detecting intraperitoneal metastasis of endometrial carcinoma with the exception of diagnosing serosal invasion. It is difficult to detect small foci of peritoneal metastasis. It is necessary to differentiate adnexal metastasis from benign adnexal masses.

Adenocarcinoma↗
PubMed1996

[Brain CT and MRI findings in fat embolism syndrome].

To elucidate brain CT and MRI findings in fat embolism syndrome (FES), we retrospectively analyzed images from 5 patients with FES during the acute and subacute stages. Brain CT examinations demonstrated brain edema in 2 patients and transient spotty low density lesions in 2 patients. Three patients showed no abnormalities. Brain MRI, however, showed brain abnormalities in all patients during the acute stages. These were revealed as spotty high signal intensity lesions on T2WI, and some showed low intensity on T1WI. These spotty lesions were considered to reflect edematous fluid occurring as a result of the unique pathophysiological condition of FES. While the spotty high signal intensity lesions on T2WI were distributed in the cerebrum, cerebellum, brain stem, thalamus, basal ganglia, internal capsule and corpus callosum, cerebral and cerebellar spotty lesions were characteristically located along the boundary zones of the major vascular territories. This characteristic location might be induced by a hypoxic brain condition in FES because the numerous fat globules present in this condition can block entire brain capillaries. This characteristic signal location on T2WI is a useful indicator for differentiating FES from the primary intra-axial brain injury in patients with multifocal trauma.

Adolescent↗
PubMed1996

Use of chloride blockers: a novel approach for cardioprotection against ischemia-reperfusion damage.

We examined whether the chloride channel blockers anthracene-9-carboxylic acid (9-AC) and 4-acetamide-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) exert protective effects against myocardial ischemia-reperfusion damage. In isolated guinea pig ventricular cells, 9-AC (200 microM), but not SITS (100 microM), inhibited the chloride current induced by isoproterenol. Electrical and mechanical activities and intracellular pH of arterially perfused guinea pig right ventricular preparations were recorded with an intracellular microelectrode, a force transducer and a pH-sensitive fluorescent probe, respectively. The preparations were subjected to 30 min of no-flow ischemia, with or without 9-AC (100 microM) or SITS (10 microM), followed by reperfusion. No-flow ischemia produced decreases in action potential amplitude and duration, and the contractile force was completely abolished. Although the changes in electrical parameters were reversed upon reperfusion, the contractile force recovered only to about 50% of preischemic values. 9-AC and SITS had no inhibitory effect on contractile force under normal conditions and during ischemia but significantly improved the recovery of contractile force upon reperfusion to about 80% of preischemic values. Both 9-AC and SITS showed significant inhibition of the ischemia-induced abbreviation of action potential duration. Other parameters were not affected by 9-AC or SITS. During ischemia, intracellular pH showed a transient small increase followed by a sustained decrease, which was completely recovered upon reperfusion. The decrease in pH during ischemia was attenuated by 80% in SITS- but not 9-AC-treated preparations. Thus, we demonstrated that the chloride channel blockers 9-AC and SITS, which have no cardiosuppressive effects, exert protective effects against myocardial ischemia-reperfusion damage.

Action Potentials↗
PubMed1996

[Intra-arterial infusion chemotherapy for liver metastases from breast cancer].

Twelve patients with liver metastases of breast cancer were treated with hepatic arterial infusion chemotherapy using 20-30 mg/body of epi-adriamycin (epi-ADM) every 2 weeks and continuous infusion of 250 mg/body/day of 5-fluorouracil (5-FU). All patients were followed by systemic chemo-endocrine therapy with oral administration of 600-1,200 mg/day of me droxyprogesterone acetate (MPA) alone or with 600-800 mg/day of 5'-deoxy-5-flurouridine (5'-DFUR). The response rate was 41.7% (5/12 cases). Duration of response was 2-28 months (mean 10 months). At one year, the survival rate was 46.8% (Kaplan-Meier method). As for side effects, gastrointestinal disturbance, bone marrow depression and alopecia were mild. These results suggest that hepatic arterial infusion therapy in combination with MPA is safe and effective for controlling liver metastases of breast cancer.

Adult↗
PubMed1996

Distribution of serum autoantibodies against G-protein-coupled cardiovascular receptors in Japanese patients with cardiomyopathy.

The prevalence of anti-receptor autoantibodies in the sera of patients with dilated cardiomyopathy has been previously demonstrated. This article will briefly review the distribution of autoantibodies against a series of G-protein-coupled cardiovascular receptors such as human beta 1 and beta 2 adrenoceptors, alpha 1 adrenoceptors, M2 muscarinic acetylcholine receptors and angiotensin II-I (AT1) receptors in a well-defined population of patients with dilated cardiomyopathy from Japan.

Autoantibodies↗
PubMed1996

[In situ detection of Epstein-Barr virus in the non-neoplastic gastric glands and infiltrated lymphocytes].

Recently, clonal EBV-DNA and/or EBV-encoded small RNA(EBER1) have been detected in some gastric carcinomas. We reported the first observation of EBV infection in gastric glands with intestinal metaplasia, and characterized the EBV-infected lymphocytes which infiltrated in gastric mucosa. To determine the cellular location of EBV, EBER1 in situ hybridization(ISH) with an EBER1 oligonucleotide probe was applied to paraffin sections of the non-neoplastic gastric mucosa in 80 cases of gastric carcinoma and 49 cases of gastric ulcer. Not only was EBER1 expression detected in the nucleus of gastric cancer cells(5 cases) but also in non-neoplastic gastric epithelial cells(3 cases) and in infiltrated lymphocytes(40 cases). A single or a few shedding non-neoplastic epithelial cells in 2 cases of EBV-associated gastric cancer showed EBER1 expression. In one case, EBER1 was observed in all of the epithelial cells of a few gastric glands with intestinal metaplasia, suggesting that the stem cells of the metaplastic gastric glands were infected with EBV. EBV DNA was also detected in the EBER1-positive metaplastic glands scratched from the paraffin section by a single cell PCR method with a BamHI W primer pair. However, immunohistochemical examination showed that these metaplastic glands lacked expression of EBNA2 and LMP-1. The observation of these rare EBV-infected metaplastic glands reinforces the pre-transformation EBV infection hypothesis for EBV-associated gastric carcinoma. The double staining using ISH and immunohistochemistry revealed that EBER1 positive lymphocytes showed a B cell marker of L26(< 50%) but not T cell markers of UCHL1 and OPD4.

B-Lymphocytes↗
PubMed1995

Quantitation of IL-1 beta mRNA by a combined method of RT-PCR and an ELISA based on ion-sensitive field effect transistor.

A method for quantitative RT-PCR using ELISA detection was developed and applied to the quantitation of IL-1 beta mRNA in clinical samples. To compensate for the 'tube effect' of RT-PCR, a synthetic RNA, pRSET RNA, was added to sample solutions as an internal standard and co-amplified with IL-1 beta mRNA. Sense primers for IL-1 beta and pRSET were labeled with digoxigenin and FITC, respectively, while anti-sense primers for both were labeled with biotin. Double-stranded PCR products were captured by two solid-phase pipettetips. One was coated with an anti-digoxigenin antibody and another with an anti-FITC antibody, and sandwiched by avidin-urease, and their activities were measured by coupling them with a pH-FET in a pH-measuring cell containing urea solution. The ratio of the signal intensity for IL-1 beta to that for pRSET was used to quantify the concentration of IL-1 beta mRNA. A calibration curve was obtained by using a known amount of AW 109 RNA as an external standard of IL-1 beta RNA. It was found that 10(2)-10(6) copies of IL-1 beta mRNA were measurable by the present method. Expression levels of IL-1 beta mRNA in clinical samples, such as monocytes of peripheral blood or synovial cells from patients with RA or OA, were determined.

Base Sequence↗