[Developmental changes in tachykinin response of the isolated rat duodenum].
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Biomedical subjects
Publications and source records attributed to K Irie.
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Since June 1984, 23 cases of progressive or recurrent breast cancers were treated with combination chemotherapy of VAM-UFT consisting of vincristine, adriamycin, mitomycin C and UFT. Clinical effects of VAM-UFT therapy were 3 CR, 12 PR, and the response rate was 65.2%. Its effective interval was 3 months. But the patients treated with over 4 cycles of VAM-UFT therapy showed an 85% response rate, with a 5-month effective interval. In each patient's background, a shorter disease free interval tended to be more highly effective, but other factors were not significant. Scirrhous carcinoma of pathology evidenced slightly high response rate. Compared with the survival time of patients treated with under 3 cycles and over 4 cycles of this therapy, the latter was significantly longer. Toxicity involved leukocytopenia (74%), thrombocytopenia (22%), anemia (30%), alopecia (91%), nausea and vomiting (87%) and stomatitis (35%), but cases in which the treatment was stopped were not observed. Therefore VAM-UFT therapy had a highly therapeutic effect, reflected in an 85% response rate, for progressive or recurrent breast cancers.
The gene coding for the nonstructural glycoprotein of dengue-2 virus was cloned, sequenced, and expressed in Escherichia coli. There was about 70% conservation at the amino acid level with dengue serotypes 1 and 4 suggesting an important common function for this protein. Conserved hydrophobic domains were found both before the amino-terminus and at the carboxy-terminus, consistent with transmembrane roles. Evidence for at least partial translocation of NS-1 through the inner membrane of E. coli was found. Also conserved were two signals for N-linked glycosylation located near the middle of NS-1. Various regions of NS-1 were tested for antigenicity with mouse and rabbit polyclonal and mouse monoclonal antibodies. The mouse polyclonal antibodies, made against a crude dengue-infected mouse brain immunogen, reacted most strongly with N-terminal regions of NS-1, whereas, the rabbit antiserum, made against purified NS-1 protein, reacted strongest with C-terminal regions. These findings suggest that immunogen presentation or species differences could be important. Although most of the monoclonals appeared to be unreactive in Western blots with expressed NS-1 proteins, two appeared to react strongly; the region from amino acid (a.a.) 273 to a.a. 346 was required for antibody binding. This region, located adjacent to the two conserved C-terminal hydrophobic domains, is highly charged and contains 5 of the 10 conserved cysteine residues of NS-1.
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A case of vulva cancer responding to the recombinant human tumor necrosis factor (rHu-TNF: PT-050), which had been administered to double inguinal lymph nodes, is herein reported. A 60-year-old female underwent resection of a vulva cancer following a diagnosis of condyloma acuminatum. After surgery, however, exacerbation of a residual tumor, sited on the right of the vulva, and metastasis of the double inguinal lymph nodes were uncovered. For treatment, rHu-TNF was injected in the inguinal lymph nodes at a dose of 1 x 10(6)U per injection, 2 times a week. After 8 therapeutic sessions for 4 weeks, a marked response was observed not only in swelling of the lymph nodes, into which rHu-TNF had been injected, but also in the tumor of primary focus, which received no injections. On the 32 nd day after the final injection of rHu-TNF, the tumor of primary focus completely disappeared and the swelling of lymph nodes had diminished to 25% of the initial volume.
We studied the release of endogenous norepinephrine (NE) from rat hypothalamic slices. The slices were superfused with Krebs-bicarbonate buffer and field-stimulated with 960 or 1800 pulses applied 40 min apart. The spontaneous and stimulation-evoked overflow of NE into the medium were both enhanced by addition of a NE reuptake inhibitor, desipramine (10 microM). Repeated stimulations in the presence of desipramine decreased the evoked release of NE during the second and third stimulation periods (S2 and S3). The attenuation of NE release during S2 was not reversed by the addition of tyrosine (50 microM) to the medium.
Metabolic activation and/or deactivation of indole alkaloid tumor promoter, (-)-indolactam V (ILV), was examined using rat liver microsomes. Reaction of ILV with the microsomes supplemented with NADPH and MgCl2 gave three major metabolites, which were identified as (-)-N13-desmethylindolactam V and two diastereomers of (-)-2-oxyindolactam V at C-3. The tumor-promoting activities of these metabolites were evaluated by induction of Epstein-Barr virus early antigen and inhibition of specific binding of [3H]-12-O-tetradecanoylphorbol-13-acetate to a mouse epidermal particulate fraction, and proved to be conspicuously lower than that of ILV. These results demonstrate that the metabolism of ILV results in detoxification, and that it itself is the tumor-promoting entity. Studies on the enzymes concerned with this metabolism suggested the involvement of cytochrome P-450-containing mixed-function oxidases. Similar deactivation seems to be possible by skin, where the mixed-function oxidases are known to exist.
New teleocidin derivatives with various substituents at positions 2, 5 and 7 of the indole ring were prepared from (-)-indolactam V, which is the fundamental structure of teleocidins and has a tumor-promoting activity, to examine the contribution of the alkyl substituents of teleocidins to the activity. Their possible tumor-promoting activities in vivo were evaluated by Epstein-Barr virus early antigen-inducing activity and inhibition of specific binding of [3H]TPA to a mouse epidermal particulate fraction. These two biological activities correlated well for each derivative. Large substituents at positions 2 and 5 remarkably lowered the activities, indicating that the structural requirements for the activities of these domains are especially strict. To investigate in detail the contribution of position 2 of (-)-indolactam V to the activities, new microbial metabolites, (-)-2-oxy-indolactam V, and blastmycetin B and C, were also tested. These compounds proved to be inactive, suggesting that the double bond at position 2 plays an important role for the activities. Substituents at position 7 generally enhanced the activities and even blastmycetin A, which is a dimer of (-)-indolactam V, showed high activities. The effects of the substituents on binding ability to the 12-O-tetradecanoylphorbol-13-acetate receptor were analyzed quantitatively using physicochemical substituent parameters and regression analysis. The results exhibited the fact that hydrophobicity of the substituents plays a critical role for receptor binding, and supported the hypothesis that the monoterpenoid moiety of teleocidins is involved in the non-specific hydrophobic interaction with phospholipids in cell membrane.
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We examined the effect of phenylalanine (50-400 microM) on the electrically stimulated release of endogenous 3,4-dihydroxyphenylethylamine (dopamine or DA) from superfused rat striatal slices. In the absence of tyrosine, phenylalanine (25 microM) partially sustained DA release, but less well than an equimolar concentration of tyrosine. In the presence of tyrosine (50 microM), phenylalanine (in concentrations of greater than or equal to 200 microM) inhibited DA release into the superfusate. This inhibition was not associated with changes in tissue levels of tyrosine or DA, nor was it mimicked by addition of high concentrations of tyrosine or leucine to the medium. We conclude that phenylalanine is a less effective precursor of DA in rat striatum than tyrosine and that it can also act to inhibit DA synthesis, depending on its concentration.
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UNLABELLED: An SF-SP Tegafur spansule preparation was administered to 26 patients with advanced cancer (24 evaluable), and the clinical effectiveness and toxicity were studied. In most of cases, daily dosages of 800 mg were administered in two parts, in a few cases, daily dosages of 1,000 mg or 1,200 mg were given. Clinical effectiveness: The evaluation of effectiveness was based on the Koyama-Saito group criteria. Of the 24 evaluable cases, PR was observed in 3 cases of gastric cancer, one of colon cancer, and one of liver cancer, a total of 5 cases (20.8%). In these 5 cases the daily dosage was 800 mg, and the median duration of PR was 51 days. TOXICITY: TOXICITY was observed in 3 (11.5%) of the 26 cases.
We measured the CA-125 value in the peripheral blood and pleural effusion of 85 patients with various types of pleural effusion using an immunoradiometric assay with a monoclonal antibody (CA-125 radioimmunoassay kit). In pleuritis with primary lung cancer, the positive rate of the CA-125 value in the peripheral blood was 53.6%. The CA-125 value in tuberculous pleural effusion was significantly lower than that in carcinomatous pleural effusion (p less than 0.02). Accordingly, this assay of CA-125 in the pleural effusion is useful in the differential diagnosis of whether the pleural effusion is tuberculous or carcinomatous.
New derivatives of (-)-indolactam V (Fig. 1), which have the basic ring-structure of teleocidins without the monoterpenoid moiety, were prepared and their Epstein-Barr virus early antigen (EBV-EA)-inducing activity was tested. (-)-14-O-Alkyl indolactam Vs (2 and 3) showed little induction of EBV-EA, while (-)-14-dehydroxyindolactam V (4) and (-)-14-chloroindolactam V (5) proved to be potent EBV-EA inducers, though their activities (EC50) were about 10 times weaker than that of (-)-indolactam V (1). These results indicate that the hydroxyl group at C-14 is not indispensable for EBV-EA induction and can be replaced. The activities (EC50) of (-)-1-N-methyl, (-)-1-N-ethyl, and (-)-1-N-butyl indolactam V (10, 11, and 12) were about 5 times weaker than that of (-)-indolactam V (1), while (-)-1-N-hexyl and (-)-1-N-octyl indolactam V (13 and 14) were even less active, suggesting that the free imino group of the indole ring in (-)-indolactam V (1) plays an important role in the activity, and that the activity cannot be enhanced by alkylation at the N-1 position of (-)-indolactam V (1).
We described gross and microscopic characteristics of 11 autopsied cases of stomach cancer with microangiopathic hemolytic anemia and/or disseminated intravascular coagulopathy. They were divided into two groups grossly. One was superficial carcinoma and the other diffuse infiltrating and fungating carcinoma. Superficial carcinoma arose multicentrically and showed figures of signet ring cell carcinoma. This condition was accompanied by marked pulmonary tumor emboli and bone marrow dissemination in the initial stage of cancer evolution. Diffuse infiltrating and fungating carcinoma arose in the corpus and showed variable histological features. Dissemination of tumor cells to the bone marrow was seen in the terminal stage. Stomach cancer in this series consisted of two different groups on gross, microscopic and metastatic features. Signet ring cell of superficial carcinoma showed characteristic biological features with respect to local extension and metastasis.
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