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Biomedical subjects

S Matsui

Publications and source records attributed to S Matsui.

At least 181 records · Page 10Linked to original sources

Immunohistochemical evaluation of alpha-catenin expression in human gastric cancer.

E-cadherin (E-cad) plays a major role in the maintenance of cell-cell adhesion in epithelial tissues, and impaired E-cad expression correlates with tumour invasion and metastasis. Alpha-catenin (alpha-cat), an undercoat protein of adherens junctions, binds to the cytoplasmic domain of E-cad and is essential for linking E-cad to actin-based cytoskeleton. We investigated E-cad and alpha-cat expression in 60 human gastric cancers immunohistochemically. The 60 gastric cancers were classified into 18 (30%) in which alpha-cat expression was preserved, and 42 (70%) reduced cases. The reduction of alpha-cat expression was significantly related to dedifferentiation, depth of invasion, infiltrative growth and lymph node metastasis. We also examined the co-expression of alpha-cat and E-cad. Seventeen (28%) tumours preserved both molecules [alpha-cat(+)/E-cad(+)] and 33 (55%) tumours reduced both [alpha-cat(-)/E-cad(-)], whereas 9 (15%) tumours exhibited alpha-cat(-)/E-cad(+). The frequency of lymph node metastasis in alpha-cat(-)/E-cad(+) tumour (67%) was significantly higher than that in alpha-cat(+)/E-cad(+) tumours (24%) and was close to that in alpha-cat(-)/E-cad(-) tumours (82%). The frequency of haematogenous liver metastasis in alpha-cat(-)/E-cad(+) tumours (44%) was significantly higher than that in alpha-cat(+)/E-cad(+) tumours (6%) or alpha-cat(-)/E-cad(-) tumours (9%). Thus, in all E-cad(+) tumours, the frequency of lymph node and liver metastasis was higher in alpha-cat(-) tumours than in alpha-cat(+) tumours. alpha-Cat expression is apparently better at predicting tumour invasion and metastasis than E-cad expression.

Adult↗

Vesnarinone prolongs survival and reduces lethality in a murine model of lethal endotoxemia.

Vesnarinone (3,4-Dihydro-6-[4(3,4-dimethoxybenzoyl)-1-piperanizyl]-2(1H)-quino linone), a recently synthesized quinolinone derivative with positive inotropic properties, has been reported the survival of patients with chronic congestive heart failure. However, the mechanisms that contribute to this improvement are not yet well understood. There is increasing evidence that vesnarinone has novel immunosuppressive properties related to its inhibition of cytokine production. Cytokines have been shown to play a pivotal role in the pathophysiologic consequences of fatal bacteremic shock. In this study, we investigated the effects of vesnarinone in a murine model of lethal endotoxemia induced by lipopolysaccharide (LPS). Eight-week-old female BALB/c mice were given 300 or 400 micrograms of LPS, and 50 or 100 mg/kg of vesnarinone was administered by oral gavage and/or 10 or 30 micrograms of vesnarinone was given intra peritoneally. Vesnarinone prolonged the median survival time and reduced lethality when given at the same time as the LPS injection. However, vesnarinone did not have a beneficial effect when administered 2 hours after LPS treatment. Plasma TNF-alpha reached a maximum level 1 hour after LPS challenge, and vesnarinone reduced the plasma level of TNF-alpha, when administered at the same time as LPS injection. Vesnarinone had protective effects against lethal endotoxemia; these effects were considered to be due to the suppression of TNF-alpha production. These findings suggest that vesnarinone may be a promising agent for the treatment of bacterial sepsis and shock.

Animals↗

Inhibition of cytokine production by a new inotropic agent, vesnarinone, in human lymphocytes, T cell line, and monocytic cell line.

Vesnarinone, a recently synthesized quinolinone derivative with positive inotropic properties, has been reported to improve survival of patients with congestive heart failure. However, the mechanisms that contribute to the increased survival are unknown. In this study, we showed vesnarinone had inhibitory effects on the production of tumor necrosis factor-alpha, interferon-gamma, interleukin-1 beta and interleukin-2 by stimulated human peripheral blood mononuclear cells, human Jurkat T cell line and THP-1 monocytic cell line. Vesnarinone may exert its beneficial effect on patients with congestive heart failure, in part, by its immunomodulating activity.

Adult↗

Immunolocalization of a fibronectin-binding proteoglycan (PG-P1) immunologically related to HSPG2/perlecan in normal and fibrotic human liver.

Immunolocalization of a fibronectin-binding proteoglycan (PG-P1) in relation to fibronectin, type IV collagen and laminin, in normal and fibrotic human liver was investigated by light and electron microscopy. HS-42, which is a monoclonal antibody to PG-P1 and is reported to recognize a heparan sulfate proteoglycan named HSPG2/perlecan, was used for this purpose. Light microscopy in the human liver with minimal changes revealed that PG-P1 was present along the hepatic sinusoids as well as fibronectin and type IV collagen, whereas laminin was only weakly detected. In portal areas, PG-P1 was only localized on basement membranes around bile duct systems and blood vessels, as well as laminin and type IV collagen, while fibronectin was scarcely detected in basement membranes. In the fibrotic liver, fibronectin was abundant in necrotic and/or newly fibrosing areas, while PG-P1 was absent in these regions. Using immunoelectron microscopy, PG-P1 was localized in the space of Disse in nearly normal livers and was only detected on basement membranes in portal tracts. In fibrotic livers, PG-P1 in the space of Disse occasionally showed a basement-membrane-like deposition in parallel with the increased light microscopical deposition of laminin in this area, suggesting the positive participation of PG-P1 in the sinusoidal capillarization. Most capillary and sinusoidal endothelial cells, and rarely bile epithelial cells revealed the reaction products of PG-P1 in their rough endoplasmic reticulum and small vesicles. Thus, it was suggested that these cell types are mainly, if not wholly, responsible for PG-P1 production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Immunosuppression by lymphokine-activated murine killer cell line with B-lymphoblast-lytic activity in vitro.

The in vitro immunosuppressive effect caused by a murine lymphokine-activated killer cell line with B-lymphoblast-lytic activity was studied. The cloned cells (named BC-1.10, phenotype Thy 1.2+, LFA-1+, TCR-alpha beta-, TCR-gamma delta-, Fc gamma RII-, CD2-, CD3 epsilon-, CD4-, CD8- and express mRNA of zeta chain) suppressed LPS-induced Ig synthesis by B lymphoblasts previously stimulated with LPS. Phase-contrast microscopy indicated disappearance of B lymphoblasts at 24 h after the addition of BC-1.10 cells. This suppressive effect was reduced when BC-1.10 cells were pretreated with anti-LFA-1 mAb, which inhibits cytotoxicity of this clone. These data suggest that the immunosuppressive effect of BC-1.10 is due to an elimination of B lymphoblasts, and that one of the physiological functions of lymphokine-activated killer (LAK) cells, which are induced as a consequence of immune reactions, might be immunosuppression.

Animals↗

Vesnarinone, a new inotropic agent, inhibits cytokine production by stimulated human blood from patients with heart failure.

BACKGROUND: Vesnarinone, a quinolinone derivative, is a recently synthesized positive inotropic agent that has been shown to dramatically improve the survival of patients with heart failure. However, the mechanism of action of vesnarinone remains unknown. Reversible neutropenia complicated with vesnarinone therapy suggests that vesnarinone may modulate the production of cytokines. Because tumor necrosis factor (TNF)-alpha and other cytokines have been shown to depress myocardial contractility, we investigated the effects of vesnarinone on the production of various cytokines. METHODS AND RESULTS: We studied the effects of vesnarinone on cytokine production by lipopolysaccharide (LPS)-stimulated whole blood from seven patients with heart failure and from five healthy volunteers. Heparinized blood was diluted in RPMI and stimulated with LPS. Vesnarinone was added in a range of 1 to 30 micrograms/mL, the blood was incubated for 24 hours, and interleukin (IL)-1 alpha, IL-1 beta, IL-6, TNF-alpha, interferon (IFN)-gamma, and granulocyte colony-stimulating factor (G-CSF) were measured by an enzyme-linked immunosorbent assay. LPS stimulation induced a more prominent increase in TNF-alpha in patients with heart failure than in healthy volunteers. Vesnarinone inhibited the production of TNF-alpha and IFN-gamma both in healthy volunteers and in patients with heart failure. IL-1 alpha and IL-1 beta were also suppressed in healthy volunteers, but this response was variable, and a significant reduction was not seen in patients with heart failure. Marked inhibition of G-CSF and other cytokines by vesnarinone was observed in one patient who had developed neutropenia as a result of vesnarinone therapy. CONCLUSIONS: Although the number of study patients was small and the results are preliminary, these findings provide evidence that vesnarinone plays an important role in the regulation of cytokines and suggest that the reduction of cytokine release may contribute to the beneficial effects of the drug in the treatment of heart failure. Furthermore, the measurement of cytokines may be useful in predicting the occurrence of neutropenia, which has been occasionally reported in patients treated with vesnarinone.

Blood↗

Treatment of virus-induced myocardial injury with a novel immunomodulating agent, vesnarinone. Suppression of natural killer cell activity and tumor necrosis factor-alpha production.

Controversy still exists concerning the therapy for viral myocarditis which manifests a wide variety of clinical symptoms. Vesnarinone, a quinolinone derivative that was developed as a positive inotropic agent with complex actions, including phosphodiesterase inhibition and cation channel modification, has recently been confirmed to improve the prognosis of patients with chronic heart failure. However, the precise mechanism of this beneficial effect is not yet clearly understood. In this study, using a murine model of acute viral myocarditis resulting from encephalomyocarditis virus infection, survival and myocardial damage were markedly improved by treatment with vesnarinone. In contrast, survival was not improved by treatment with amrinone, a phosphodiesterase inhibitor. Although vesnarinone did not inhibit viral replication or protect myocytes from viral direct cell injury, it did inhibit the increase in natural killer cell activity after viral infection. On the other hand, amrinone failed to inhibit natural killer cell activity. Both vesnarinone and amrinone suppressed the production of tumor necrosis factor-alpha. Therefore, we postulate that vesnarinone exerted its beneficial effects through an inhibition of natural killer cell activity, and that it serves as an immunomodulator providing new therapeutic possibilities for the treatment of viral myocarditis and/or immunological disorders.

Amrinone↗

Periodic lateralized epileptiform discharges in EEG during recovery from hyponatremia: a case report.

PLEDs were observed in a case of undifferentiated schizophrenia, transiently during the course of recovery from hyponatremia, and diffuse EEG slowing remained even after the serum sodium had returned to normal range. It was considered that PLEDs had occurred transiently in relation to hemispheric ischemic disturbance induced by hyponatremia. The characteristics of PLEDs associated with hyponatremia will need to be studied further in more patients with hyponatremia.

Consciousness Disorders↗

Transient expression of [D-Ala2] deltorphin I-like immunoreactivity in prenatal rat small intestine.

We studied the distribution of immunoreactive elements for [D-Ala2] deltorphin I (DADTI), a delta-opioid receptor ligand, in fetal and postnatal rat small intestine. DADTI-like immunoreactive cells were detected transiently on embryonic Days 20 and 21. Electron microscopic examination revealed that positive staining occurred in mucous epithelial cells, either mature goblet cells or undifferentiated cells containing only a few mucous granules. Positive immunoreaction products in mature goblet cells were confined in their apical cytoplasm to the luminal parts of mucous granule aggregates. The result suggests that a DADTI-like molecule(s) is synthesized in rat intestinal goblet cells and is secreted in a diacrine fashion into the intestinal lumen at a late fetal period. The molecule(s) thus secreted may be important for the intestine of rats just before birth, because DADTI-like immunopositive goblet cells are no longer seen at any postnatal period.

Amino Acid Sequence↗

[Clinical bacteriology and empiric therapy for hospital-acquired pneumonia in the elderly at a national leprosarium].

Hospital-acquired pneumonia is one of the most important fatal respiratory diseases in the elderly. Prompt and precise empiric therapy is essential for recovery. Fourteen isolates from twelve elderly lepromatous leprosy patients (9 men, 3 women, mean age of 75.8 years) with hospital-acquired pneumonia were studied. Subsequently, empiric therapy with gentamicin and beta-lactams for nosocomial pneumonia in the elderly was examined. Fourteen types of bacteria isolated from expectorated sputum specimens consisted mainly of ten strains of gram-negative bacilli (71%) six of Klebsiella pneumoniae, one each of Citrobacter freundii, Enterobacter agglomerans, Serratia liquefaciens, and Aeromonas hydrophilia and four strains of gram-positive cocci (29%) two of Staphylococcus sp., one each of Streptococcus sp. and Streptococcus pneumoniae. Methicillin-resistant Staphylococcus aureus and Pseudomonas sp. were not detected. Resistance rates of the etiologic agents to the antibiotics showed that gentamicin was 7.7%, ceftazidime 0%, and cefmetazole 23.1%. Cephalosporins were superior to penicillins. As a result of empiric therapy, six elderly leprosy patients with nosocomial pneumonia were cured and one improved temporarily. This study shows the necessity of specific empiric therapy for hospital-acquired pneumonia in a hospital with many elderly patients. The combination of gentamicin and beta-lactams is of value as an initial antibiotic therapy for hospital-acquired pneumonia in the elderly.

Aged↗

[A case of severe pneumonia in an elderly man, caused by Citrobacter freundii suspected to have a low susceptibility to imipenem/cilastatin sodium].

An 80-year-old blind man with lepromatous leprosy suffered from right femoral neck and humeral neck fractures on July 9, 1993. Because of fever (38.6 degrees C), difficult expectoration and diffuse bilateral perihilar infiltrates with consolidation in the left lower lung field on his chest radiograph, severe pneumonia was diagnosed. With intravenous hyperalimentation, imipenem/cilastatin (IPM/CS), ceftazidime, minocycline, gentamicin (GM), and human immunoglobulin were administrated. On July 29, hip screw-plate fixation was done. Citrobacter freundii was isolated from the sputum and its susceptibility was IPM/CS+, GM3+. Multi-drug therapy with GM and other antibiotics improved the patients' condition, but Citrobacter freundii were still detected and 43 days of medication were needed. According to a report by the Ministry of Health and Welfare in 1992, the resistance rate of IPM/CS against Citrobacter freundii is only 0.7%, and IPM/CS is more effective than beta-Lactams. This is a very rare case of severe pneumonia in an elderly patient caused by Citrobacter freundii that was suspected to have low susceptibility to IPM/CS.

Aged↗

[A case of drug induced pneumonitis caused by saiboku-To].

We report a case of drug induced pneumonitis caused by Saiboku-To. A 60-year-old woman was admitted to our hospital because of dry cough, fever and severe dyspnea after taking Saiboku-To. Blood gas analysis showed marked hypoxemia. Chest X-ray obtained on admission showed diffuse ground glass shadows in bilateral lung fields, and computed tomography showed diffuse interstitial shadows. Following steroid pulse therapy, clinical symptoms, hypoxemia and chest X-ray findings were ameliorated. Against medical advice, she took another Chinese medicine with ingredients similar to those of Saiboku-To. She complained of dry cough, fever and dyspnea and the chest X-ray again revealed diffuse ground glass shadows in both lung fields. Lymphocyte stimulation test against Saiboku-To and the patch test for Saiboku-To were positive. Therefore, we diagnosed this case as having pneumonitis due to Saiboku-To. This is first report of interstitial pneumonitis due to Saiboku-To.

Alveolitis, Extrinsic Allergic↗

Immunohistochemical detection of alpha-catenin expression in human cancers.

The function of E-cadherin is thought to be regulated by its associated cytoplasmic proteins including alpha-catenin. To determine whether possible downregulation of alpha-catenin expression may play a role in tumor invasion and metastasis through the dysfunction of E-cadherin, we investigated the expression of alpha-catenin in human carcinoma samples (esophagus, stomach, and colon) by immunohistochemistry using our monoclonal antibody against alpha-catenin (alpha-18). Normal epithelium expressed alpha-catenin strongly without exception. However, alpha-catenin expression was frequently reduced in primary tumors of esophagus (12 of 15:80%), stomach (14 of 20: 70%), and colon (8 of 10: 80%). Of the tumors with reduced alpha-catenin expression, alpha-catenin expression was completely negative in 70.6% of them (9 of 12 in esophagus, 9 of 14 in stomach, and 6 of 8 in colon). These results also suggested that some human cancer cells may have impaired E-cadherin-mediated cell adhesiveness through the downregulation of alpha-catenin expression.

Adenocarcinoma↗

Kinetic analysis of mutual metabolic inhibition of lidocaine and propranolol in rat liver microsomes.

The metabolic interaction between lidocaine (LD) and propranolol (PL) was analysed kinetically in rat liver microsomes. Employing a very short incubation time of 30 sec, we demonstrated that PL competitively inhibited liver microsomal 3-hydroxylation of LD, but did not affect either the formation of monoethylglycinexylidide or methylhydroxylidocaine from LD in PL concentrations up to 1 microM. On the other hand, LD competitively inhibited PL 4-, 5- and 7-hydroxylations, but the inhibition type of LD for PL N-desisopropylation could not be clarified. Comparison of the kinetic data for liver microsomes from Wistar and Dark Agouti rats indicated that among the primary metabolic pathways of LD, the Vmax value for 3-hydroxylation was markedly less in female Dark Agouti rats. The results suggest that LD 3-hydroxylation and PL ring hydroxylations are mediated by the same isozyme(s) belonging to the CYP2D subfamily.

Animals↗

Successful total removal of intramedullary hemangioblastoma from the medulla oblongata.

The case of a large solid hemangioblastoma embedded wholly in the medulla oblongata is reported. Preoperative magnetic resonance imaging provided precise indications of the anatomical location and radiologic features of the tumor, which facilitated its total removal by microsurgery. Short-latency somatosensory evoked potentials were monitored throughout the operation.

Adult↗