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Biomedical subjects

S Goto

Publications and source records attributed to S Goto.

At least 667 records · Page 37Linked to original sources

[Serial changes in hemostatic molecular markers after urokinase therapy of acute myocardial infarction].

We have examined the changes in fibrinolysis after urokinase administration for 6 patients with acute myocardial infarction. Patients were treated with urokinase with doses between 960,000 and 1,440,000 units, and fibrinolytic activities were determined by using newly developed molecular markers: alpha 2-plasmin inhibitor (alpha 2-PI), plasminogen, alpha 2-PI plasmin complex (PIC) and FDP D dimer. We also used classical hemostatic tests such as prothrombin time (PT) and plasma fibrinogen level. These tests were measured with 1 to 2 hour intervals, during the first 6 hours of therapy, daily during the next 3 days, and subsequently on day 7 and 14. The initial intravenous administration of urokinase with a dose of 460,000 units produced a significant decrease in alpha 2-PI level, but induced only minimal changes in the level of fibrinogen, FDP-E, and FDP D-dimer, suggesting that enhancement of fibrinolytic activity was less pronounced under such therapy. This might be due to the ability of residual amounts of alpha 2-PI to sufficiently inhibit plasmin generation in the circulating blood. However, a subsequent injection of 960,000 units of urokinase into the coronary artery induced a profound reduction in the alpha 2-PI to an unmeasurable level, and resulted in a marked enhancement of fibrinolytic activity. The elevation of FDP-E and FDP D-dimer was accompanied with this decrease in alpha 2-PI and persisted for more than 6 hours after urokinase injection. Prolongation of PT due to decrease in fibrinogen level was also observed over 6 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Relationship between venous invasion and hematogenous metastasis in the colorectal cancer patients].

We investigated the correlation between venous invasion and hematogenous metastasis. In thirteen patients with colorectal carcinoma, depth of invasion (ss.s or a1.a2) was the same. Four cases had hepatic metastasis at operation (group A), 3 cases were identified with hematogenous recurrence after operation (group B), and 6 cases were disease free over 10 years after operation (group C). Specimens were all step-sectioned and serial sections were stained both with HE and EM. Results were as follows. 1. Venous invasion was found in all cases and average rates of venous invasion (ARVI) of groups A and B were higher than that of group C (A; 7.8%, B; 6.3%, C; 2.1%, p less than 0.05). 2. In ss.s layer, ARVI of group A and B were higher than that of group C (A; 6.1%, B; 6.2%, C; 1.5%, p less than 0.05). 3. Rates of venous invasion to larger veins (diameter greater than 200 microns) were higher in group A than in others (A; 53.5%, B; 25.6%, C; 7.9%, p less than 0.05), and those to the middle-sized veins (diameter; 50-200 microns) were higher in group B than in others. These facts suggest that cancer invasion to the veins located in ss.s (a1.a2) layer or ranged in diameter over 200 microns relates to hematogenous metastasis.

Colorectal Neoplasms↗

Automated homogeneous liposome immunoassay systems for anticonvulsant drugs.

We developed automated homogeneous immunoassays, based on immunolysis of liposomes, for measuring phenytoin, phenobarbital, and carbamazepine from serum. Liposome lysis was detected spectrophotometrically from entrapped glucose-6-phosphate dehydrogenase activity. The procedure was fully automated on a routine automated clinical analyzer. Within-run, between-run, dilution, and recovery tests showed good accuracies and reproducibilities. Bilirubin, hemoglobin, triglycerides, and Intrafat did not affect assay results. The results obtained by liposome immunoassays for phenytoin, phenobarbital, and carbamazepine correlated well with those obtained by enzyme-multiplied immunoassay (Syva EMIT) kits (r = 0.995, 0.986, and 0.988, respectively) and fluorescence polarization immunoassay (Abbott TDx) kits (r = 0.990, 0.991, and 0.975, respectively). The proposed method should be useful for monitoring anticonvulsant drug concentrations in blood.

Anticonvulsants↗

[The perineal implantation of a bladder tumor through urethro-vasal reflux].

Perineal implantation of urinary bladder cancer in a 57-year-old male is reported. The patient had been suffering from incomplete paraplegia and neurogenic bladder for these 29 years because of accidental injury of lumbar spinal cord with episodes of bladder stones two times and right epididymitis three times, and presented urinary leakage from a perineal fistula. The fistula orifice was surrounded by a hard mass lesion. Bilateral swelling of inguinal lymph nodes was present. Fistulogram and voiding cysto-urethrography revealed reflux from posterior urethra to the fistula through right vas and epididymis. Histological diagnosis of resected perineal mass and biopsied left inguinal lymph node was transitional cell carcinoma with predominant metaplasia of squamous cell carcinoma. Tissues obtained by TUR-biopsy of a mass lesion at bladder wall was also histologically diagnosed transitional cell carcinoma with metaplasia of squamous cell carcinoma. The present case indicates implantation of a bladder tumor to perineum by urethero-vasal reflux and metastases to inguinal lymphnodes from the perineal lesion.

Carcinoma, Squamous Cell↗

[Shape change in human megakaryoblastic leukemia cells, MEG-01].

We investigated the intracellular processes of the shape change in the human megakaryoblastic leukemia cell, MEG-01, by platelet agonists. Thrombin induced the formation of many pseudopods. This shape change was also induced by TPA and A23187, but not by ADP, collagen, or epinephrine. Electron microscopy and FITC-labeled phalloidin staining revealed thick submembranous microfilament bundles in the pseudopods of the shape-changed cells induced by thrombin. Shape change was inhibited by cytochalasin B. Protein kinase C (RKC) inhibitor, H-7, markedly inhibited thrombin-induced shape change, while the myosin light chain kinase (MLCK) inhibitor, ML-9 did not. These results suggest that thrombin-induced reorganization of microfilaments and shape change of MEG-01 cells are mediated by PKC but not by MLCK.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Purification, characterization, and amino acid sequences of pepsinogens and pepsins from the esophageal mucosa of bullfrog (Rana catesbeiana)

Two pepsinogens (pepsinogens 1 and 2) were purified from the esophageal mucosa of the bullfrog (Rana catesbeiana), and their molecular weights were determined to be 40,100 and 39,200, respectively, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The NH2-terminal 70-residue sequences of both pepsinogens are the same, including the 36-residue activation segment. Furthermore, a cDNA clone encoding frog pepsinogen was obtained and sequenced, which permitted deduction of the complete amino acid sequence (368 residues) of one of the pepsinogen isozymogens. The calculated molecular weight of the protein (40,034) coincided well with the values obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results are incompatible with the previous report (Shugerman R. P., Hirschowitz, B. I., Bhown, A. S., Schrohenloher, R. E., and Spenney, J. G. (1982) J. Biol. Chem. 257, 795-798) that the major pepsinogen isolated from the bullfrog esophageal gland is a unique "mini" pepsinogen with a molecular weight of approximately 32,000-34,000. The two pepsinogens were immunologically indistinguishable from each other and related to human pepsinogen C. The deduced amino acid sequence was also more homologous with those of pepsinogens C than those of pepsinogens A and prochymosin. These results indicate that the frog pepsinogens belong to the pepsinogen C group. They were both glycoproteins, and therefore, this is the first finding of carbohydrate-containing pepsinogens C. Both pepsinogens were activated to pepsins in the same manner by an apparent one-step mechanism. The resulting pepsins were enzymatically indistinguishable from each other, and their properties resembled those of tuna pepsins.

Amino Acid Sequence↗

Immunoreactive alpha A crystallin in rat non-lenticular tissues detected with a sensitive immunoassay method.

For the quantitative analysis of the A subunit of alpha crystallin (alpha A) in the lens and for the survey of possible existence of alpha A in the non-lenticular tissues, we have established a highly sensitive and specific immunoassay method for alpha A. Antisera to alpha A were raised in rabbits with alpha A purified from bovine lens, or the C-terminal decapeptide (EEKPSSAPSS) of alpha A (alpha Apep). The antibodies to alpha A and alpha Apep were purified by the use of an alpha A-coupled Sepharose 4B column. The F(ab')2 fragments of purified anti-alpha A IgG were immobilized on polystyrene balls and the Fab' fragments of purified anti-alpha Apep IgG were labeled with beta-D-galactosidase from Escherichia coli. The minimum detection limit of the sandwich-type immunoassay using the two antibody preparations was less than 10 pg alpha A without any cross-reactivity with alpha B. By employing the present methods, it was found that a significant amount of immunoreactive alpha A was present in rat spleen and thymus. Very low levels of immunoreactive alpha A were detected in the rectum, caecum, liver, kidney, adrenal, cerebellum and brainstem. The immunoreactive alpha A in the spleen extract was purified partially (about 50% purity) by the use of anti-alpha Apep-coupled Sepharose. The concentration of alpha A in the spleen was less than 1 ng/mg protein before 3 weeks of age. After 5 weeks of age, however, it increased lineally reaching about 20 ng/mg protein by 18 weeks of age. Immunohistochemically, the alpha A was localized in the reticular cells in the spleen and thymus.

Animals↗

Brain-specific small RNA transcript of the identifier sequences is present as a 10 S ribonucleoprotein particle.

BC-1 RNA is a small RNA transcript of the identifier repetitive sequences present in rodent genomes. The RNA has been reported to be specific to the brain and confined to the cytoplasm. The RNA level increases during the 1st month after birth. To understand its cytoplasmic function, it seems important to examine whether BC-1 RNA is present as an RNP. It is believed that the protein component may govern the functions of BC-1 RNA in the brain cells. In the present report, we have demonstrated that BC-1 RNA is not free but complexed with proteins to form a 10 S RNP in the cytoplasm. We have also shown that the 10 S RNP is not associated with cytoplasmic structures such as polysomes/ribosomes or microsomes. The buoyant density of the RNP was 1.26 g/cm3 in metrizamide. Furthermore, some of the protein components were shown to be in direct contact with RNA, since photo-cross-linking adducts of protein to BC-1 RNA were identified upon UV irradiation of the 10 S BC-1 RNP.

Animals↗

Role of type III homology repeats in cell adhesive function within the cell-binding domain of fibronectin.

Recombinant fibronectin (FN) fragments and their mutant proteins were produced to elucidate the role of type III homology repeats in cell adhesive activity within the cell-binding domain of FN. Cell adhesive activity of the 11.5-kDa fragment, the cell attachment site of the cell-binding domain, was less than 0.1% that of native FN despite the presence of the Arg-Gly-Asp-Ser sequence. The activity increased as type III homology repeats were added to the N terminus of the 11.5-kDa fragment, and a 52-kDa fragment with four additional type III repeats had almost the same activity of native FN. Deletion of Arg-Gly-Asp from the fully active fragments completely abolished the cell adhesive activity. Deletion of one or two repeats from the 52-kDa fragment affected the extent of the cell adhesive activity, the degree of the effect being inversely correlated with the distance of the deletion from the type III repeat containing Arg-Gly-Asp-Ser. Rearrangement of type III repeats caused much loss of activity. These results suggest that the number and kinds of type III repeats and their correct alignment rather than the putative synergistic site decide the extent of the specific cell adhesive activity.

Amino Acid Sequence↗

Catecholaminergic neurons in the parabrachial nucleus of normal individuals and patients with idiopathic Parkinson's disease.

The parabrachial nucleus is believed to play a role in autonomic regulation. We have used the Fontana-Masson ammoniacal silver nitrate method and a tyrosine hydroxylase-immunostaining technique to demonstrate the presence of neuromelanin-containing catecholaminergic neurons in the parabrachial nucleus of normal individuals. In addition, we also show that there is a significant reduction of these catecholaminergic neurons and presence of Lewy bodies in the parabrachial nucleus of patients with idiopathic Parkinson's disease. These findings may be related to the several autonomic disturbances that may occur in idiopathic Parkinson's disease.

Catecholamines↗

Preparation and evaluation of Eudragit gels. I: Eudragit organogels containing drugs as rectal sustained-release preparations.

New organogels containing salicylic acid, sodium salicylate, procaine, and ketoprofen were prepared by using Eudragit L and S, and propylene glycol. The physical properties (e.g., penetration and extensibility) of the organogels were affected considerably by the incorporation of a basic drug, such as procaine, rather than an acidic drug, such as salicylic acid. In in vivo evaluation using rabbits, it was found that 30% Eudragit L organogels containing 1.25% (w/w) salicylic acid or 2.5% (w/w) ketoprofen showed sustained plasma salicylic acid or ketoprofen levels and almost the same AUC as compared with Witepsol H-15 suppositories containing these drugs. Furthermore, the relative bioavailability for salicylic acid and ketoprofen released from 30% Eudragit L organogels, with 10% (w/w) linolic acid or oleic acid as absorption enhancer, increased to 1.55-1.75- and 1.46-1.85-fold, respectively, compared with 30% Eudragit L organogels without these unsaturated fatty acids.

Acrylic Resins↗

Preparation and evaluation of Eudragit gels. II: In vitro release of salicylic acid, sodium salicylate, and ketoprofen from Eudragit L and S organogels.

The in vitro dissolution characteristic of salicylic acid, sodium salicylate, and ketoprofen from Eudragit L and S organogels was investigated by the rotation disk method. The dissolution pattern of salicylic acid and erosion of Eudragit L polymer from the organogels followed apparent zero-order kinetics, providing strong evidence for a surface erosion mechanism and negligible diffusional release of salicylic acid. On the other hand, the dissolution of salicylic acid from Eudragit S organogels was a linear function of the square root of time. The apparent dissolution rate of salicylic acid from Eudragit S organogels increased with increasing temperature from 32 to 42 degrees C and agitation rate from 50 to 200 rpm. A linear relationship was obtained between the logarithm of apparent dissolution rate constants and the reciprocal of absolute temperatures. The activation energy for release of salicylic acid from Eudragit S organogels was in the range of 2.99 to 5.57 kcal/mol. From various experimental results, it was concluded that the release process of salicylic acid from Eudragit S organogels was diffusion controlled through the organogels matrix.

Acrylic Resins↗

Participation of collagenase and elastase in LPS-induced airway hyperresponsiveness in guinea pigs.

Bacterial lipopolysaccharide (LPS) cause airway hyperreactivity in guinea pigs pretreated with metopirone. LPS inhalation resulted in an increase in airway muscarinic reactivity measured by intravenous acetylcholine injection 1-4 h after the inhalation of LPS. The increase of pulmonary capillary permeability was observed 1-24 h after the inhalation of LPS, whereas the increase of leukocytes in bronchoalveolar lavage fluid (BALF) was observed 2 and 24 h after the inhalation of LPS. Increased cells are mainly neutrophil, eosinophil, and macrophage. From the histopathological study, acute mucosal injury and loss of epithelial cilia were observed 1-24 h after the inhalation of LPS. In order to investigate the phlogistic substance in LPS-induced hyperreactivity, the roles of collagenase and elastase were investigated. The activities of both enzymes were elevated 2 h after the inhalation of LPS. The inhalation of collagenase and elastase caused bronchial hyperreactivity and increased pulmonary permeability. The combined administration of prednisolone (10 mg/kg/day) and cyclophosphamide (10 mg/kg/day) for five days decreased LPS-induced hyperreactivity, pulmonary capillary increase, collagenase and elastase activities, and the number of nucleated cells in BALF 2 h after the inhalation of LPS. These results indicate the participation of collagenase and elastase in the onset of LPS-induced airway hyperreactivity in guinea pigs.

Acetylcholine↗

Growth inhibitory effect of bestatin on choriocarcinoma cell lines in vitro.

Bestatin, one of the biological response modifiers (BRMs), is an inhibitor of aminopeptidase B (AP-B), leucine aminopeptidase (LAP) and aminopeptidase M (AP-M). In this report, we investigated the direct effect of bestatin on the growth of cancer cells in vitro using established four choriocarcinoma cell lines. In vitro chemosensitivity was evaluated by the succinate dehydrogenase inhibition (SDI) test. Bestatin showed the growth-inhibitory effect on all the choriocarcinoma cell lines dose-dependently, especially on NaUCC-4 cells. Both an isomer of bestatin with no inhibitory activity against aminopeptidases, (2R, 3S)-AHPA-(R)-Leu, and another isomer with stronger inhibitory activity against AP-B than bestatin, (2S, 3S)-AHPA-(R)-Leu, did not show growth inhibition on NaUCC-4 cells. So it is suggested that one of the possible mechanisms responsible for the direct action of bestatin on the choriocarcinoma cells may be related to the inhibition of activity of LAP or AP-M rather than that of AP-B. Furthermore, cytotoxicity of actinomycin D on the choriocarcinoma cells was significantly enhanced by combination with bestatin. These results suggest that bestatin has not only an indirect host-mediated anti-tumor activity, but also a direct growth-inhibitory effect on some kinds of cancer cell lines.

Aminopeptidases↗