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Y Ino

Publications and source records attributed to Y Ino.

At least 91 records · Page 5Linked to original sources

[Comparative studies of nafamostat mesilate and various serine protease inhibitors in vitro].

Inhibitory effects of nafamostat mesilate (nafamostat) on various enzymes were investigated, and they were compared with those of gabexate mesilate (gabexate), leupeptin, aprotinin and urinastatin in vitro. Nafamostat inhibited trypsin, plasmin, thrombin, pancreatic kallikrein, Clr and Cls more potently than gabexate and leupeptin. Gabexate and leupeptin did not inhibit pancreatic kallikrein and thrombin, respectively. Aprotinin inhibited trypsin, plasmin, pancreatic kallikrein and chymotrypsin. Urinastatin inhibited trypsin and chymotrypsin. Nafamostat inhibited the complement-mediated hemolysis in diluted serum more potently than gabexate and leupeptin, but aprotinin and urinastatin did not. Nafamostat, furthermore, inhibited the complement-mediated hemolysis in undiluted serum, but gabexate did not. Unlike aprotinin and urinastatin, nafamostat and gabexate inhibited alpha 2-macroglobulin bound trypsin as well as free trypsin to the same extent. The inhibitory effect of gabexate toward trypsin was reduced more markedly than that of nafamostat after incubation with plasma at 37 degrees C. These results show that nafamostat is more useful than other inhibitors such as gabexate, leupeptin, aprotinin and urinastatin.

Aprotinin↗

Pharmacological studies of FUT-175, nafamostat mesilate. V. Effects on the pancreatic enzymes and experimental acute pancreatitis in rats.

Effects of FUT-175 on the pancreatic enzymes in vitro and in vivo in the enterokinase-induced experimental acute pancreatitis were investigated, and they were compared with those of gabexate and aprotinin. In in vitro experiments, FUT-175 inhibited the pancreatic protease activities 10 to 100 times more potently than gabexate. Furthermore, FUT-175 inhibited the enterokinase activity. Unlike aprotinin, FUT-175 inhibited alpha 2-macroglobulin bound trypsin activity as well as free trypsin. In in vivo experiments, at doses of 0.5-50 micrograms/kg/min, FUT-175 suppressed the elevated protease activities in the experimental acute pancreatitis more potently than gabexate. Differently from the action of aprotinin, FUT-175 suppressed trypsin activities both in the pancreas and in the plasma to the same extent. Furthermore, FUT-175 reduced the mortality of rats in the experimental acute pancreatitis in a dose-dependent manner. These data strongly support that FUT-175 is clinically useful in the therapy of acute pancreatitis.

Acute Disease↗

Inhibitory effects of a novel synthetic protease inhibitor, FUT-175, on the paw edema in rats and zymosan-induced complement activation in vitro.

FUT-175 inhibited the zymosan-induced rat paw edema in a dose-dependent manner, while indomethacin exhibited no significant activities in this model. FUT-175 also inhibited the decrease in hemolytic complement (CH50) induced by zymosan in vitro, and indomethacin was inactive. These results suggest that FUT-175 has potent in vitro and in vivo inhibitory activity against the activation of the complement system induced by zymosan.

Animals↗

The principal pathway from the piriform cortex to the deep amygdaloid nuclei in the cat.

Pathways relaying olfactory information to the deep amygdaloid nuclei (AMYGd) were analyzed with electrophysiological techniques in anesthetized cats. Stimulation of the piriform cortex (PC) produced orthodromic spikes in some AMYGd neurons with a mean latency of 12.2 ms and antidromic responses in other neurons with a mean latency of 9.3 ms. Stimulation of the AMYGd produced antidromic spikes in some PC neurons with a mean latency of 11.5 ms. Some neurons in the entorhinal area (EA) were activated orthodromically from the PC with a mean latency of 22 ms, and a proportion of these cells was also activated antidromically from the AMYGd. Some neurons in the agranular insular cortex were activated orthodromically from the PC, but none of them responded antidromically to AMYGd stimulation. From these observations, it is suggested that olfactory information reaches the AMYGd directly from the PC or indirectly via the EA, and that the direct path conveys the major olfactory input from the PC to the AMYGd.

Amygdala↗

Carbohydrate antigen defined by a monoclonal antibody raised against a gastric cancer xenograft.

A monoclonal antibody, ST-4-39, was obtained by using a human gastric cancer xenograft, St-4, as an immunogen. Immunization was achieved by transferring immunocompetent mouse spleen cells into a nude mouse bearing St-4. Hybridomas were produced with the spleen cells of the mouse after rejection of the tumor and screened for immunohistochemical reactivity with cancers and normal tissues on formalin-fixed paraffin sections. ST-4-39 immunohistochemically reacted with various cancers including gastric, colorectal and pancreatic cancers as well as some normal tissues. ST-4-39 and NS 19-9 differed in immunohistochemical reactivity, although they reacted with some cancers and a few normal tissues in common. PBS extracts of normal and cancer tissues were examined for antigen reactive with ST-4-39 by sandwich enzyme immunoassay. Extractable antigen was detected in adenocarcinomas of colon, stomach and lung, while it was detected only in salivary gland and trachea among normal tissues examined. Gel filtration analysis of the antigen indicated a molecular weight of greater than or equal to 1 X 10(6), and the antigenic determinant was suggested to be a carbohydrate chain with terminal sialic acid by studies using periodic acid, neuraminidase and pronase treatments. Furthermore, the ST-4-39 antigen affinity-purified from two gastric cancer strains was shown to contain multiple carbohydrate determinants including sialyl-Lewisa and sialyl-Lewisx, suggesting the antigen to be a mucin.

Animals↗

Expression of carbohydrate antigen 19-9 and stage-specific embryonic antigen 1 in nontumorous and tumorous epithelia of the human colon and rectum.

The expression of carbohydrate antigen 19-9 (CA 19-9) and stage-specific embryonic antigen 1 (SSEA-1) in various human colorectal epithelia was examined by an immunohistochemical method. In mucosa remote from the carcinoma, CA 19-9 was not expressed, whereas SSEA-1 was only faintly expressed in lower crypts in all cases. In mucosa adjacent to the carcinoma, CA 19-9 was weakly expressed in upper crypts in 20% of the cases, whereas SSEA-1 was expressed not only in lower crypts in all cases but also in upper crypts in 93.3% of the cases. In adenoma, CA 19-9 was expressed in 80.6% of the cases, and SSEA-1 was expressed in all cases. The expression of both antigens was to some extent related to the degree of cellular atypia. In focal carcinoma in adenoma, CA 19-9 was strongly and diffusely expressed in 50% of the cases, and SSEA-1 was strongly and diffusely expressed in all cases. In advanced carcinoma, CA 19-9 was homogeneously or heterogeneously expressed in 82.2% of the cases, and SSEA-1 was homogeneously or heterogeneously expressed in all cases, but lower intensity of SSEA-1 staining was associated with a decrease in the degree of carcinoma differentiation. These results show that the expression of both CA 19-9 and SSEA-1 changes along with neoplastic transformation and progression in the colon and rectum. Immunohistochemical studies of SSEA-1 in flat colorectal mucosa might be a useful approach for detecting foci with preneoplastic change in the general population, whereas those of SSEA-1 and CA 19-9 could be a useful method for detecting focal carcinoma in adenoma.

Adenoma↗

Pharmacological studies of FUT-175, nafamstat mesilate. I. Inhibition of protease activity in in vitro and in vivo experiments.

FUT-175, 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate (nafamstat mesilate), a novel synthetic protease-inhibiting agent, was studied to determine its in vitro effects against various proteases and other enzymes, as well as to determine its in vivo protease inhibitory effects. FUT-175 was found to inhibit, in an intense, specific and reversible way, the enzyme activities of trypsin, C1r, C1s, thrombin, kallikrein and plasmin with IC50 values of the order of 10(-6)-10(-8) M. FUT-175 also inhibited complement-mediated hemolysis, including both classical and alternative pathways, sites of inhibition being on C1r and C1s as evidenced by the intermediate-cell technique. In animal model reactions in which the complement system is known to be involved as pathogenetic factors, e.g., Forssman shock, Forssman cutaneous vasculitis, zymosan-induced paw edema, endotoxin shock and local Shwartzman reaction, FUT-175 was highly effective in that, for example, intravenous dosing at 3 mg/kg could completely protect guinea pigs from the lethal Forssman shock. FUT-175 was also found to be effective in trypsin-induced shock in mice, in lethality due to thrombin-thrombosis in mice and in kinin formation in the inflammatory process in rats.

Animals↗

Distribution of blood group antigens A, B, H, and I(Ma) in mucus-producing adenocarcinoma of human lung.

The distribution of blood group antigens A, B, and H and their precursor antigen I(Ma) in the mucus of lung cancer patients was studied histochemically. Antigens A, B, and H compatible with the ABO status of the patients were expressed in the mucus of bronchial gland mucous cells and bronchial goblet cells except in a few patients presumed to be nonsecretors , while antigen I(Ma) was not expressed at all in these cells. In contrast, compatible antigens A, B, and H were decreased or not present in cancer cells but antigen I(Ma) accumulated. Accumulation of antigen I(Ma), which resulted from incomplete synthesis of antigens A, B, and H, was a tumor-associated phenomenon in the mucus of the lung and was found in all patients examined. However, the degree of this accumulation varied from patient to patient, and tumor cells showed marked heterogeneity even in an individual case. In addition, accumulation of antigen associated with loss of antigens A and B was demonstrated in cancer cell mucus of patients with a blood group status other than O. Expression of incompatible blood group antigen reactive with anti-A serum (A-like antigen) also was detected in cancer cell mucus of blood group B patients.

ABO Blood-Group System↗

[Pharmacological studies of FUT-175, nafamstat mesilate. III. Anti-inflammatory activities of FUT-175].

Anti-inflammatory effects of FUT-175 (nafamstat mesilate), a new synthetic serine protease inhibitor, on various types of experimental inflammation were investigated in vivo and in vitro, in comparison with non-steroidal anti-inflammatory drugs (NSAID). The in vivo studies showed that FUT-175 has the abilities to inhibit almost all types of inflammatory reactions employed in the present study. In particular, being evaluated on the basis of the effect of indomethacin, FUT-175 exhibited relatively higher potencies against some reactions such as zymosan-induced increase of vascular permeability, scald paw edema, zymosan-induced granuloma-pouch, the Arthus reaction and acetic acid-induced writhing in which the complement system or the kallikrein-kinin system are considered to play an important role. The in vitro studies showed that FUT-175 is quite different from NSAID, that is, FUT-175 had no effects on heat-induced erythrocyte-lysis and heat-induced denaturation of bovine serum albumin. FUT-175 also had no effect on chemotaxis of polymorphonuclear leucocytes, but inhibited the production of chemotactic factor by antigen-antibody reaction. These above results suggested that FUT-175 has a different mode of action from NSAID and that serine protease inhibiting activities of this compound might play an important role in its anti-inflammatory effect.

Animals↗

Histochemically demonstrable changes in cell surface carbohydrates of human germ cell tumors.

Cell surface carbohydrate chains of human germ cell tumors were investigated histochemically using peanut agglutinin (PNA), Dolichos biflorus agglutinin (DBA), Ulex europaeus agglutinin I (UEA-1), and anti-I-(Ma) antibody. Of 16 cases of embryonal carcinoma in adult testis, peanut agglutinin, a lectin specific for terminal beta-galactosyl residues, bound to the surface of tumor cells in 11 cases, D. biflorus agglutinin, a lectin specific for terminal alpha-N-acetyl galactosamine residues, in 10, and U. europaeus agglutinin, a lectin specific for terminal alpha-L-fucosyl residues in 7. I-(Ma) antigen, a branched carbohydrate chain composed of three N-acetyl lactosamine units, was found in 12 cases as well. The cell surface of tubular or organoid architecture tended to be positive for some of these four reagents, whereas that of a papillary pattern tended to be negative. All yolk sac tumors (three in adult testis, 10 in infantile testis, and four in ovary) were positive for peanut and U. europaeus agglutinins and anti-I-(Ma) antibody but were negative for D. biflorus agglutinin. Seventeen of 18 seminomas (in adult testis) and one dysgerminoma (in ovary) did not react with these four reagents. Four choriocarcinomas (three in testis and one in ovary) were not positive for any of them either. In 10 cases of immature teratoma, the appearance of the binding sites to these lectins and antibody depended on the direction of differentiation and the degree of maturity. These findings suggest that carbohydrate chains of human germ cell tumors change greatly in the process of differentiation from embryonal carcinoma cells to somatic cell (teratoid) component or yolk sac carcinoma component, and that histochemical detection of the binding sites described may assist in the classification of germ cell tumors, in spite of the lack of precise knowledge about the biologic role of cell surface carbohydrates.

Adult↗

Distribution of blood group antigens and CA 19-9 in gastric cancers and non-neoplastic gastric mucosa.

The distribution of blood group ABH antigens, their precursor I(Ma) antigen, Lewis a antigen and monoclonal antibody-defined tumor-associated antigen CA 19-9 in gastric cancers and their surrounding non-neoplastic mucosa was studied by using immunohistochemical methods. ABH antigens were localized in the foveolar epithelium except for a few cases presumed to be non-secretors, but ABH antigens were lost focally from metaplastic mucosa. In contrast, Lewis a and I(Ma) antigens were present in the foveolar epithelium of non-secretors and metaplastic mucosa where ABH antigens were not detected. Gastric cancers also showed focal loss of ABH antigens and gain of Lewis a and I(Ma) antigens, and the cancer cells showed marked heterogeneity in antigen expression compared with non-neoplastic mucosa. Expression of incompatible blood group antigen (A-like antigen) reactive with monoclonal anti-A antibody was also detected in cancer cells of blood group O and B cases. CA 19-9 (sialylated-Lewis a) was detected in 62% of gastric cancers and in the restricted areas of gastric mucosa where Lewis a was positive.

ABO Blood-Group System↗

A non-thalamic olfactory pathway to the orbital gyrus in the cat.

Extracellular unit responses were recorded from the cortical layer of the orbital gyrus following stimulation of the piriform cortex fronting on that gyrus. The responses were obtained only from the dorsal bank of the rhinal sulcus. The responses were presynaptic axon and postsynaptic soma spikes with latencies of about 4 and 4.8 msec, respectively. When the dorsal bank of the rhinal sulcus was stimulated, antidromic responses with a latency of about 4.4 msec were recorded from the superficial and deep soma layers of the piriform cortex. Following injections of horseradish peroxidase into the dorsal bank of the rhinal sulcus, labeled cells were found in the piriform cortex, the lateral, basolateral and central amygdaloid nuclei, and the prelimbic area. These results indicate that the piriform cortex projects directly to part of the orbital gyrus by way of association fiber pathways.

Animals↗

High risk ratio on mortality and characteristics of malignancies in dialysis patients.

A questionnaire study was done in order to clarify the risk ratios on the mortality of malignancy and the characteristics of malignancies in dialysis patients. The risk ratios were 4.2 times in males and 7.5 times in females greater than those among the age adjusted general population respectively. The average interval from the first dialysis to the clinical onset of malignant disease was 12 months. About a half of the patients died within 3 months. Frequencies of death in colon cancer, especially rectum, uterus and liver were higher in dialysis patients. Dialysis patients died of malignancies belonged to the older group of the dialysis patient population, however they were younger comparing with those died of malignancies in the general population.

Adolescent↗

Distribution of alpha-fetoprotein and immunoreactive carcinoembryonic antigen in human hepatocellular carcinoma and hepatoblastoma.

The distribution of alpha-fetoprotein (AFP) and immunoreactive carcinoembryonic antigen (CEA) in 62 hepatocellular carcinomas (HCC) and five hepatoblastomas (HBL) all surgically removed was studied by an immunohistochemical method, and the results were compared with the levels of the antigens in the patients' serum. AFP was present as coarse granules in the cytoplasm of immature tumor cells. AFP-positive tumor cells were detected in 34/43 cases (79.1%) with serum AFP levels higher than 400 ng/ml and in 1/24 (4.2%) of the remaining cases. They were present in 8/32 (25%) cases of relatively well-differentiated HCC (Edmondson's grade I or II), 22/32 (68.8%) of relatively poorly differentiated HCC (Edmondson's grade III or IV), and 5/5 of HBL. An antigen immunoreactive with a conventional rabbit anti-CEA immunoglobulin (DAKO) but not with a murine monoclonal anti-CEA antibody (Hybritech) was present on the surface of bile canaliculi of both non-neoplastic and neoplastic hepatocytes. This CEA cross-reactive differentiation antigen was more often found in relatively well-differentiated tumors, and the presence of this antigen in tumors did not correlate with patients' serum CEA levels. In conclusion, CEA of an oncofetal nature was not produced by either HCC or HBL.

Carcinoembryonic Antigen↗