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Biomedical subjects

S Shimada

Publications and source records attributed to S Shimada.

At least 397 records · Page 22Linked to original sources

Antitumor activity of deoxyribonucleic acid fraction from Mycobacterium bovis BCG. I. Isolation, physicochemical characterization, and antitumor activity.

A fraction extracted from Mycobacterium bovis strain BCG, which was composed of 70.0% DNA, 28.0% RNA, 1.3% protein, 0.20% glucose, and 0.1% lipid and of no detectable amounts of cell wall components such as alpha, epsilon-diaminopimelic acid and hexosamine, was found to possess strong antitumor activity. Repeated intralesional injection of this fraction, designated MY-1, without attachment to oil or a single intralesional injection of MY-1 emulsified in mineral oil caused the IMC carcinoma of CDF1 mice and line 10 tumor of strain 2 guinea pigs to regress and/or prevented metastasis very effectively. MY-1 after digestion with RNase, which contained 97.0% single-stranded DNA with a guanine-cytosine content of 69.8%, was more effective than undigested MY-1 against IMC and line 10 tumor, while MY-1 digested with DNase, which contained 97.0% RNA, had reduced activity, suggesting that the DNA from BCG possessed strong antitumor activity under certain conditions. Details of the extraction procedures and physicochemical characterization of MY-1 were also described.

Animals↗

[Clinical trial on the effect of tegafur (SF-SP)].

SF-SP capsules containing sustained release granules of tegafur were orally administered 800 mg, b.i. d. for more than 4 weeks in 20 cases of advanced cancer, 11 of whom were evaluable (stomach 7, colon 1, liver 1, bile 1 and pancreas 1). The evaluation of antitumor effects was based on criteria of the Japan Society for Cancer Therapy, which are are almost the same as those of WHO. One partial remission out of 7 cases of stomach cancer was obtained, and its duration was 40 weeks. Toxicities were anorexia, nausea and vomiting, diarrhea and stomatitis, one case each of anorexia, and nausea and vomiting occurred within 10 days after SF-SP administration. No bone marrow depression, hepatic and renal disorders occurred after long-term SF-SP administration. SF-SP seems to be useful in the treatment of patients with gastric cancer.

Adenocarcinoma↗

[A double-blind comparison between cefaclor and cephalexin in the treatment of dental infections].

A comparative clinical study of cefaclor (CCL) with cephalexin (CEX) was carried out by randomized double-blind techniques in order to contemplate the clinical efficacy, side effects and usefulness in treatment of 243 patients with dental infections. In the CEX group, CEX was orally administered 4 times a day at a daily dosage of 1,000 mg for 3 to 5 days. In the CCL group, CCL was orally administered 3 times a day at a daily dosage of 750 mg for 3 to 5 days and 1 capsule of placebo was also given every evening in order to keep the blindness of the administration. Evaluable cases for efficacy of athe drugs were 213 consisting of 108 for CCL and 105 for CEX. There were no significant differences in background of the patients and severity of the disease between 2 treatment groups. Clinical effectiveness on the 3rd day was 89.7% in CCL group and 78.6% in CEX group, showing significant difference between 2 treatment groups. Clinical effectiveness on the final day of administration was 94.4% in CCL group and 92.4% in CEX group, showing no significant difference between 2 treatment groups. Side effects were found in 10.5% of 114 patients receiving CCL and in 4.5% of 112 patients with CEX, and there was no significant difference between 2 treatment groups. The side effects were mostly gastrointestinal origin. According to the judgement by physicians in charge, no significant difference was seen in clinical usefulness between the 2 drugs.

Adult↗

Histochemical study of phosphorylase in proliferating cells of intestinal metaplasia and carcinoma of the human stomach.

A morphologic histochemical study of phosphorylase was carried out to investigate the relationship between gastric carcinoma and intestinal metaplasia. Intense phosphorylase activity was observed in the carcinoma cells, especially in well-differentiated adenocarcinoma, and in the proliferating cells of some intestinal metaplasias. Metaplastic epithelium other than the proliferating cells occasionally showed a positive reaction. Phosphorylase was negative in normal gastric epithelium, even in its proliferating cells. There was an apparent coincidence between the location of well-differentiated adenocarcinoma and the distribution of intestinal metaplasia, with the proliferating cells showing positive reaction for phosphorylase. These data suggest that the relationship between the proliferating cells of intestinal metaplasia showing phosphorylase activity and well-differentiated adenocarcinoma is apparently closer than the much-debated relationship between the epithelium of intestinal metaplasia and gastric carcinoma.

Adenocarcinoma↗

Automated analysis of alditols by anion-exchange chromatography with photometric and fluorimetric postcolumn derivatization.

Eight alditols were separated in ca. 80 min as their borate complexes by stepwise elution with three borate buffers on a column packed with Hitachi 2633 resin. The alditols in the eluate were derivatized automatically to colored, fluorescent products by applying sequential reactions of periodate oxidation and Hantzsch condensation, and the products were detected either photometrically or fluorimetrically. This automated method allowed simultaneous determination of 20-500 and 20-200 nmol amounts of alditols by photometric and fluorimetric monitorings, respectively. The lower limits of detection were ca. 2 and 0.5 nmol, respectively. The interference by aldoses was slight. Aldoses may be also determined as alditols by direct injection of aqueous solutions to which excess amounts of sodium borohydride have been added. This method was applied with success to urinary alditol assay and to molecular weight determination by end group analysis.

Adult↗

The immunomodulatory action of inosiplex in relation to its effects in experimental viral infections.

The effect of inosiplex (Isoprinosine) on viral replication, experimental viral infections and host immune functions has been examined. Inosiplex was found to have a broad spectrum of antiviral activity, inhibiting the RNA viruses, influenza (INFV) and parainfluenza (PIV), as well as the DNA viruses, herpes simplex (HSV) and vaccinia (VACV). However, the antiviral effects were modest when compared to amantadine and adenine arabinoside (ARA-A). Inosiplex in vivo caused a statistically significant increase in survival of treated animals (hamster, mice) infected with RNA or DNA viruses. This effect of inosiplex was apparent in animals which were previously immunosuppressed. Inosiplex, at optimal dose, conferred total protection in treated mice against secondary influenza infection. Since this was accompanied by statistically significant increases in serum anti-hemagglutinin and anti-neuraminidase titers, an effect of inosiplex on host defenses against secondary viral infection was implicated. This effect was further demonstrated by passive transfer of protection by splenocytes from inosiplex-treated donors to untreated recipients. Inosiplex was found to enhance the mitogen- (PHA-, ConA and MLC-) induced blastogenesis of lymphocytes from untreated mice. The LPS response was not affected. Inosiplex added in vitro caused a dose-dependent increase in the primary immune anti-SRBC response in vitro, as determined by direct and indirect PFC; there was also a dose-dependent effect on the secondary in vitro direct and indirect PFC responses. Inosiplex in vivo enhanced the primary immune response to SRBC, as determined by direct PFC assay; this was also the case for immunosuppressed mice. The drug enhanced delayed type hypersensitivity to picryl chloride in the mouse. Macrophage function was also enhanced by inosiplex, as was apparent from phagocytosis of SRBC. Gamma interferon production from murine lymphocytes was augmented by inosiplex in vitro. Treatment with inosiplex had no effect on natural killer cells or on antibody dependent cellular cytotoxicity. Thus, the pronounced effect of inosiplex on secondary viral infections may result through two different mechanisms: a direct antiviral effect and an elevation of multiple parameters of host immunity, which are usually compromised during viral infection. The latter mechanism may be the more important.

Adjuvants, Immunologic↗

Elevated immunoglobulin M levels in low birth-weight neonates with chronic respiratory insufficiency.

Ten babies weighing less than 1500 g at birth subsequently developed chronic respiratory insufficiency and bubbly appearance on chest X-ray during their infancy. The clinical diagnoses were compatible with Wilson-Mikity syndrome. They were compared with very low birth-weight infants who did not show these signs and symptoms. On the first day (mean) of life significantly high serum immunoglobulin M levels were found in the study group. The possibility exists that the chronic respiratory insufficiency seen in these very low birth-weight infants may have been caused by intrauterine infection.

Female↗

Evidence for "response to injury" hypothesis.

Role of platelet-derived growth factor (PDGF) in myointimal thickening described in "response to injury" hypothesis was investigated with artery of rats in culture and with air-injured artery of rats. PDGF promoted cell growth in ring preparation of carotid artery in culture denuded with citrate. It did not promote any cell growth in preparations without denudation. Trapidil, a PDGF antagonist, inhibited the cell growth promoted by PDGF in the denuded arterial ring. Systemic injection of PDGF was performed for 8 days to rats with thrombocytopenia induced by injections of anti-platelet serum. This treatment caused myointimal thickening of carotid artery 10 days after denudation by means of air injury. Trapidil at oral intake levels of 1, 3 and 30 mg/kg/day inhibited this change observed in denuded site of artery. Trapidil at oral intake of 6 mg/kg/day also inhibited myointimal thickening observed 15 days after denudation of carotid artery by air injury in normotensive and spontaneous hypertensive rats both with normal platelet counts. These results evidenced the role of PDGF in myointimal thickening described in "response to injury" hypothesis and clinical use of trapidil may be a new approach to the treatment of atherosclerosis.

Animals↗

Antithrombotic activity and the mechanism of action of trapidil (Rocornal).

Antithrombotic activity and the mechanism of action of trapidil were investigated, as compared with those of aspirin and dipyridamole. Trapidil at oral doses of 30 and 100 mg/kg inhibited arterial thrombosis in rats, while aspirin and dipyridamole at doses up to 300 mg/kg showed only a mild activity. This action may be explained by the fact that trapidil at concentrations ranging from 139 microM to 251 microM exerted 50% inhibition of platelet aggregation induced by ADP, arachidonic acid, thrombin or thromboxane A2 mixture, inhibition of platelet release reaction induced by ADP, arachidonic acid or thrombin, disaggregatory effect on aggregated rabbit platelets by arachidonic acid and potentiating action on antiaggregatory action of prostacyclin in vitro. In vitro actions of trapidil were apparently different from those of aspirin and dipyridamole. Trapidil also showed inhibition of platelet phosphodiesterase activity and thromboxane synthetase activity. Trapidil was expected to be an effective antithrombotic agent. The antithrombotic action of trapidil may be mediated by the inhibition of platelet function which is characterized by the inhibition of both thromboxane synthetase and phosphodiesterase activities, and by the potentiation of the antiaggregatory action of prostacyclin.

Adenosine Triphosphate↗