The biologically active constituents of Ganoderma lucidum (Fr.) Karst. Histamine release-inhibitory triterpenes.
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Biomedical subjects
Publications and source records attributed to M Uchida.
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An original electric drill nephroscope was developed for percutaneous nephroureterolithotomy (PNL). In 8 cases large pelvic calculi over 1 cm in diameter were successfully disintegrated and removed.
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The metabolism of 6-mercaptopurine (6-MP) in L-1210 mouse leukemia cells and human chronic myelocytic leukemia cells (CML cells) was examined. The acid-soluble fractions obtained from cells incubated with [8-14C]6-MP were chromatographed on a Dowex-1 formate resin column using a formic acid linear gradient elution system. Chromatography of the extract of L-1210 cells revealed four principal radioactive peaks. The fraction containing the third peak was hydrolyzed by snake venom 5'-nucleotidase (Crotalus adamanteus). Cellulose thin layer chromatography revealed that the radioactive peak of the hydrolysate corresponded to 6-thioguanosine. The results showed that 6-MP was converted to 6-thioinosinic acid (6-TIMP) and 6-thioguanylic acid (6-TGMP) in L-1210 cells. In order to elucidate the pathway of 6-MP conversion to 6-TGMP, we examined the interaction of [8-14C]6-TIMP and purified IMP dehydrogenase. It was found by DEAE-cellulose thin layer chromatography that the IMP dehydrogenase converted 6-TIMP to 6-thioxanthylic acid (6-TXMP). Dowex-1 chromatography of the acid-soluble extract of human CML cells incubated with [8-14C]-6-MP also revealed a radioactive peak corresponding to 6-TGMP. These results suggest that 6-MP is metabolized to 6-TGMP by serial conversion to 6-TIMP and 6-TXMP through the de novo GMP synthetic pathway in L-1210 cells and human CML cells.
An open study was carried out in 12 male, healthy volunteers to investigate the renal tolerance of ofloxacin, a new, broad-spectrum oral antibacterial agent. Subjects received single doses of 300 mg and then repeated doses of 300 mg ofloxacin twice daily for 7 days. Urine was collected in several fractions during the study and the excretion of creatinine, alanine-aminopeptidase (AAP), gamma-glutamyl transferase (GGT) and n-acetyl-beta-glucose aminidase (NAG) was calculated in 12-hour fractions. Serum creatinine, beta 2-microglobulin concentrations and creatinine clearance were also determined. Based on the findings for the kidney enzymes AAP, GGT and NAG, renal tolerance was good. This was confirmed by creatinine clearance and serum beta 2-microglobulin values. Ofloxacin showed no nephrotoxic potential in this study.
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A Phase II study of UFT for head and neck cancer was conducted in 10 institutions. UFT is a mixture of Futraful and uracil. Eighty-four patients entered this trial, of which 60 were evaluable. UFT was administered orally at a daily dose of 600 mg/day. Eight patients achieved complete response and 10 achieved partial response with an over-all response rate of 30.0 %. Evaluating response according to by histology, the response rate was 30.9% for cases of squamous cell carcinoma. Complete response was observed in one case of undifferentiated carcinoma. Response rate according to primary site was 33 to 40% for the nose & paranasal sinuses, mesopharynx, hypopharynx and larynx. The response rate was 28.9% for the group of patients treated previously, and 33.3% for the group previously untreated. The mean time for 50% or more regression of the tumor was 4.3 weeks. Toxic effects appeared in 40.3% of 67 evaluable cases as anorexia, nausea, vomiting, stomatitis, diarrhea etc. In one case of maxillary carcinoma, severe bone marrow suppression was observed. We concluded that UFT therapy was markedly effective for head and neck cancer.
A 65-year-old woman with early invasive squamous cell carcinoma of the tongue is reported. Atypical but not definitely malignant epithelium was detected by cytology, although the gross appearance of the glossal lesion looked like early invasive squamous cell carcinoma. On the surgical material, the basal and para-basal cell layers were occupied by cancer, but the upper portion of the epidermis from the prickle cell layer through the surface of the mucosa was histologically benign. In such cases, to obtain the correct diagnosis on cytology, repeated examinations as well as using a sharp instrument like a curatte are necessary.
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Twenty-four patients with various solid tumors including metastatic liver cancer and cancer of the lung, gallbladder, and pancreas were treated with a lipophilic macromolecular drug, copoly(styrene-maleic acid) conjugated neocarzinostatin (SMANCS). The drug was dissolved in a lipid contrast medium Lipiodol and administered by catheterizing the respective feeding arteries under x-ray monitoring. The advantages of this therapy include: (1) selective deposition of Lipiodol with the anti-cancer drug in the target tumor, (2) a pronounced and long-lasting anti-cancer effect, (3) enhanced visualization of the tumor on x-ray examinations for a prolonged period which also facilitated the long-term follow-up, (4) semiquantitative evaluation of the dosage regimen by x-ray examination before further administration, (5) general applicability due to procedural simplicity, and (6) little side effect. Since the amount of Lipiodol and SMANCS used per administration for a patient (1.0-5.0 ml; 1.0-5.0 mg) was far less than the anticipated toxicity (LD50 of Lipiodol = 95 ml/60 kg, dog, intravenously; and that of SMANCS = 3.4 mg/kg, mouse, IV), no deleterious effects to such critical organs as the brain, heart, lung, liver, or kidneys were observed upon radiologic and general clinical examination.
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The study concerned the effects of lidocaine and mepivacaine on rat mast cell histamine release. At low concentrations these drugs inhibited the histamine release induced by concanavalin A and compound 48/80 although, at high concentrations, they caused cell lysis. The mechanism of their inhibition of histamine release was studied by examining the pH dependence of the inhibitory action. In the absence of drugs, the release of histamine was not affected by the pH of the medium, but the inhibitory effects of the drugs increased with increase in pH. The percent inhibition of histamine release by these drugs at each pH was plotted against the calculated concentration of the nonionized form of the drug, according to the Henderson-Hasselbalch equation. The inhibitory action was correlated with the concentration of nonionized molecules, which readily penetrate the cell membrane. From the interaction of lidocaine with the phospholipid bilayer, it was concluded that this drug penetrates the lipid bilayer and that this effect increases with increasing pH of the medium. Thus, it seems that it is the nonionized form of local anesthetics that inhibits histamine release and that it is nonionized molecules that penetrate the mast cell membrane.
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