Application of functional monomers for dental use (Part-9). Syntheses of succinoxy methacrylates and their adhesion to polished and etched tooth surfaces.
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Biomedical subjects
Publications and source records attributed to M Kawaguchi.
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Using B16 melanoma variant subline B16-B14b, which was selected in vivo for enhanced brain surface colonization abilities in C57BL/6 mice, we have examined ultrastructurally the cellular behavior of B16 melanoma cells during the process of cerebral invasion. Within 14 days after the injection of viable tumor cells (10(5) cells/0.2 ml) into the common carotid artery, gross nodular tumors were identifiable in the cerebral cortex. Tumor cells in the boundary area of the cerebral cortex and leptomeninges breached the limiting glial membrane with numerous small cytoplasmic protrusions and invaded into the brain parenchyma by direct extension or along blood vessels. Direct invasion into the brain parenchyma was characterized by two ultrastructural features of the tumor cells: the production of many elongated cytoplasmic protrusions at zones of invasion which separated, fragmented, and eventually engulfed nervous tissue; and the formation of tumor cell attachments to the dendrites of nerve cells via tight junction-like structures. Another mechanism of brain parenchyma infiltration by the melanoma cells was invasion and migration along blood vessel walls of the cerebral capillaries. In this case B16 melanoma cells were found attached directly to the basolateral side of the blood vessel basal lamina. The tumor cells appeared to achieve their basal lamina location by pushing aside the perivascular astrocytes.
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A chemoimmunotherapy program designed on the basis of experimental results was administered to 27 patients with stage III carcinoma of stomach following curative resection. The treatment regimen consisted of active immunotherapy with Vibrio cholerae neuraminidase (VCN)-treated autologous tumor cells admixed with bacillus Calmette-Guérin (BCG) and chemotherapy with drugs such as cyclophosphamide (CY), mitomycin C (MMC), and 5-fluorouracil (FU) which proved to enhance the immune response when administered at optimal dose and timing. Then, it was followed by long-term administration of tegafur (FT) and immunomodulators. This treatment significantly improved survival when compared to that of 41 historical control patients treated with surgery alone (P less than 0.001). As compared to 31 control patients concurrently treated with a bolus dose of MMC followed by long-term FT and immunomodulators, survival had a tendency, but not significantly, to be improved in patients treated with this therapy (P less than 0.1). However, the survival rate at 4.5 years was significantly higher than that of control patients (P less than 0.01). These results appeared to show that this type of adjuvant combination chemoimmunotherapy may be of benefit for this group of patients with gastric carcinoma.
Eighty-nine patients with advanced gastric carcinoma were treated with a combination chemo-immunotherapy regimen that consisted of active immunotherapy with Vibrio cholerae neuraminidase (VCN) treated autologous tumor cells admixed with BCG and drugs including cyclophosphamide, mitomycin C (MMC) and 5-fluorouracil, followed by long term tegafur (FT) and immunomodulators. This treatment significantly improved survival rate of patients in Stages III, IV and unresectable or recurrent carcinoma, compared to that of historical controls. As compared to controls treated with MMC followed by long term FT and immunomodulators concurrently, survival rate of those in Stage III tended to improve (P less than 0.1) and survival rate at 4.5 years in Stage III was significantly higher (p less than 0.01), although it was not improved in Stage IV. In patients with unresectable or recurrent tumor, survival time was not significantly lengthened with this therapy when compared with that in patients given BCG alone in the same treatment schedule (CCI-BCG group). However, none of 19 patients in CCI-BCG group survived more than 15 months, although 4 of 28 patients receiving this therapy survived. These results suggest that this combination chemo-immunotherapy is effective for a selected group of patients with advanced gastric carcinoma.
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The effect of cyclic GMP on the accumulation of p-aminohippurate (PAH) was investigated by using rat kidney cortical slices. When the slices were preincubated with cyclic GMP and thereafter incubated in the absence of the cyclic nucleotide for the assay of PAH transport, cyclic GMP inhibited PAH accumulation in the slices in a dose-dependent fashion. Pretreatment of the slices with dibutyryl cyclic GMP induced no inhibition of PAH uptake, but that with the combination of cyclic GMP and butyrate inhibited the accumulation to the same extent as did cyclic GMP. Guanosine and its monophosphate (GMP) had no effect on PAH accumulation in the slices. Inhibitory effect of cyclic GMP on PAH accumulation was not due to the changes of electrolyte content and water distribution in the slices. The slices pretreated with cyclic GMP at 0 degree C failed to decrease PAH accumulation. Cyclic GMP had no effect on organic cation (tetraethylammonium, TEA) transport in the slices. These evidence suggest that cyclic GMP may be able to modulate the rat renal transport system for PAH although this study does not explain the mechanism of inhibition of PAH transport by the cyclic nucleotide.
This report dealt with the effects of dimercaprol (BAL) and thiotic acid (TA), antidotes against arsenical, on the distribution and the excretion of 74As in several organs of the rat. Each organ was removed and served for quantitative analysis of 74As five days after subcutaneous injection of Na374AsO3 5 microCi/100 g. Administration of BAL or TA was performed intraperitoneally with a single administration or five consecutive administrations for five days before animals were sacrificed. 74As content in each organ of the rat decreased to a greater extent in the five consecutive administration group of BAL or TA than in the non-treated or single administration groups. Moreover, the excretion of 74As in a digestive tract increased more remarkably in the five consecutive administration group than in the non-treated or single administration groups. There were no differences in the excretion or the content of 74As in each organ between the single administration group and the non-treated group.
Antitussive effect, toxicity and other related pharmacological properties of dl-1,2,9,10-tetramethoxy-6a,alpha-aporphine phosphate (dl-glaucine phosphate, DL-832) were studied in comparison with those of codeine. Acute toxicity of DL-832 in mice was 2/5 to 7/10 of that of codeine for any routes of i.v., i.p., s.c. and p.o. The antitussive effect as tested by "coughing dog and cat" methods and Domenjoz's method in cats was 1/5 to 4/5 that of codeine, according to the routes administered. Safety margin in antitussive effect was similar to or less than that of codeine. Differing from codeine, levallorphan exerted no influence on the antitussive effect of DL-832. In vitro, DL-832 exerted moderate relaxant actions on normal tone and on contractions induced by histamine and acetylcholine of tracheal muscle. In vivo, it showed a moderate relaxant effect on histamine-induced bronchial constriction. The decrease in the volume of respiratory tract fluid caused by DL-832 was smaller than that by codeine. DL-832 slightly reduced the transportation rate of intratracheal foreign body, although to much lesser extent as compared to codeine. On respiration, blood pressure and heart rate, DL-832 showed depressant effects and moreover it caused changes in ECG. However, all of these effects were similar to and a little weaker than those observed with codeine. DL-832 prolonged hexobarbital sleeping time significantly. Neither analgesic nor anticonvulsant effect was observed. When given in larger doses, DL-832 inhibited intestinal transportation in vivo, although this effect was much weaker than that of codeine. DL-832 showed slight local anesthetic effect.