[Investigation of endogenous prostaglandins in DMH induced colonic cancer in rats].
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Biomedical subjects
Publications and source records attributed to M Koike.
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Awake, unanesthetized, and paralyzed sheep made hypoxic and acidotic were given equivalent low and high intravenous doses of lidocaine and bupivacaine over 10 sec. Within 30 sec of injections, all animals had electroencephalographic evidence of convulsions. After administration of low-dose lidocaine, arrhythmias associated with significant hemodynamic changes did not occur; after administration of high-dose lidocaine, half of the animals became hypotensive but had no arrhythmias other than sinus tachycardia. However, after administration of low-dose bupivacaine, all sheep had evidence of serious electrocardiographic changes or arrhythmias, and one animal died. After administration of high-dose bupivacaine, serious electrocardiographic changes occurred in all animals, and despite resuscitative efforts, all died. The most common abnormality after bupivacaine administration was a wide-QRS-complex bradycardia, occurring in most animals regardless of dose. Two-thirds of the animals given high-dose bupivacaine had electromechanical dissociation and subsequent refractory asystole. Although the mechanism of action is not known, bupivacaine appears to be more cardiotoxic than lidocaine. This toxicity is enhanced in animals by the presence of hypercarbia, acidosis, and hypoxia.
The effect of the variation of urinary pH on the pharmacokinetics of the acidic antibacterial agent, cinoxacin (pKa 4.60), was examined. Urinary pH of 24-h fasted rats remained at about pH 6 during the daytime, while that of nonfasted rats was high (about pH 7.5) in the morning and gradually decreased to a pH similar to that of the fasted rat in the afternoon. The free fraction of cinoxacin in fasted rat sera in the morning was similar to that in nonfasted rats despite the longer half-life of cinoxacin in fasted rats. In the afternoon the free fraction was slightly different despite similar cinoxacin elimination in fasted and nonfasted rats. These findings seemed to exclude the contribution of protein binding from the causes of increased cinoxacin elimination in nonfasted rats in the morning. Elimination rate constants of cinoxacin obtained with a one-compartment open model correlated well with urinary pH 30 min after injection, suggesting that the urinary pH plays a more important role in cinoxacin elimination. When cinoxacin was orally administered to fasted rats at 11:00, the area under the plasma concentration-time curve was threefold larger than in nonfasted rats. As found with the intravenous administration, this difference may be explained by the prolonged half-life caused by decreased urinary pH after fasting. This study revealed the time-dependent elimination of cinoxacin in nonfasted rats, which is related to physiological change of urinary pH caused by food intake.
A case of malignant epithelioid hemangioendothelioma of the liver mimicking veno-occlusive disease is reported. The histological, ultrastructural, and immunohistochemical features of the present case indicate striking similarities to epithelioid hemangioendothelioma (EHE) of the soft parts described by Weiss and Enzinger. Tumour metastasis to the lung gave a picture closely resembling intravascular bronchiolo-alveolar tumour (IVBAT) of the lung. EHE of the liver is considered to be a unique type of hepatic endothelial neoplasm behaving as a low grade malignant tumour with a veno-occlusive process which has rarely been described, and had previously been classified as other diseases or neoplasms.
Light and electron microscopic findings in papillary endothelial hyperplasia of the mandible in a 49-year-old female are reported. The endothelial cell-lined papillary projection into a cystic lumen was examined by light microscopy and characteristic features of the endothelial cells were found by electron microscopy. Factor VIII-related antigen was demonstrated in the endothelial cells by the immunoperoxidase technique.
A procedure for rapid separation and microquantitative determination of various alpha-keto acids in serum and urine was developed. The procedure used reverse-phase high-performance liquid chromatography of the alpha-keto acids after derivatization into fluorescent quinoxalines by reaction with o-phenylenediamine. Deproteinization of serum with tungstic acid or methanol facilitated a constant recovery of alpha-keto acids. The useful range of analysis of seven alpha-keto acids by isocratic chromatography was from 10 to 250 pmol. The fluorescence emission was measured at 410 nm with excitation at 350 nm. The data obtained from samples of patients with chronic pyruvic acidemia and maple syrup urine disease, confirmed the usefulness of the method in clinical applications. A slightly modified procedure was needed for the analysis of oxaloacetic acid and phenylpyruvic acid.
Controversy persists about the cardiac toxicity of bupivacaine if accidentally administered intravenously during regional anesthesia. Using awake, unanesthetized sheep, we evaluated the cardiac effects of low and high equivalent doses of lidocaine and bupivacaine given intravenously over 10 s. All animals convulsed within 30 s of injections. Although both drugs significantly increased heart rate and systemic and pulmonary arterial blood pressure for up to 10 min, cardiac output was affected variably. The magnitude of hemodynamic changes that each drug produced did not differ significantly from each other at either dose level. However, of the sheep receiving intravenous lidocaine, none developed arrhythmias other than mild sinus tachycardia and minimal ST-T wave changes (which occurred in 25% of the animals). After intravenous bupivacaine injection, all sheep had transient changes on the EKG and/or arrhythmias (e.g., supraventricular tachycardia; atrioventricular condition blocks; ventricular tachycardia; multiform premature ventricular contractions; wide QRS complexes; ST-T wave changes; and in one animal, fatal ventricular fibrillation). Normal sinus rhythm usually returned within 8-10 min. Arterial blood gas and acid-base values stayed within the normal range during the studies, and serum potassium did not change significantly from control. In conclusion, in conscious adult sheep, equivalent doses of lidocaine or bupivacaine produced similar central nervous system (CNS) toxicity when rapidly injected intravenously. In the absence of marked hypoxia, respiratory or metabolic acidosis, hyperkalemia, or hypotension, serious cardiac arrhythmias occurred after bupivacaine but not lidocaine.
For prevention of nosocomial infection, 25 infants including high risk patients received an emergency injection of live varicella vaccine. Three patients developed a rash within 5 days after vaccination, but their symptoms were mild. The other 22 showed no clinical symptoms and gave an immune response. Twenty-two patients receiving immunosuppressive therapy were vaccinated and 20 of them showed a positive response in the varicella skin test. Of 14 vaccinated patients with malignancies, 2 giving a positive skin test, later showed clinical varicella, but their symptoms were not severe. One case with ALL was immunized safely under very poor conditions during the first induction therapy. No complications were observed in any patients.
A human cancer cell line (ZK-1) has been established from a well-differentiated squamous cell carcinoma of the tongue. The cytokeratin polypeptides pattern of ZK-1 cells consists of four major polypeptides with molecular weights between 46 and 58 kilodaltons (kd). Antibodies raised against the purified 58 kd cytokeratin filament from cultured ZK-1 cells were shown to be specific by one- and two-dimensional polyacrylamide gel electrophoresis, immunofluorescence, and immunoelectron microscopy. Immunoprecipitation studies showed that the antibody reacted mainly with the 58 kd cytokeratin. The distribution of the 58 kd cytokeratin in both sparse and confluent cultures was analyzed by the indirect immunofluorescence technique. In both cases, it appeared that fibrillar arrays extended throughout the cytoplasm running over the nucleus and toward cell-to-cell boundaries. Thick bundles of filaments were seen in confluent cultures, especially in large and flattened keratinized cells. Characteristically, reactions were also seen in the intercellular boundaries, appearing as "dots." Electron microscopy using immunoperoxidase techniques indicated that the 58 kd cytokeratin was localized in tonofilaments, tonofilaments attached to desmosomes, desmosomal plaques and membrane-coating granules.
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We observed a 3-month-old Japanese female infant with severe psychomotor retardation, coarse facial appearance, hepatosplenomegaly, and dysostosis multiplex. Only beta-galactosidase was found to be deficient when the routine lysosomal hydrolase assay was performed on the patient's lymphocytes at 6 months of age. At first GM1-gangliosidosis type 1 seemed the most likely diagnosis. Later, however, additional studies (hydrolase assay in cultured skin fibroblasts, urinary oligosaccharide analysis, genetic complementation study, etc.) revealed that biochemical data of this case were in agreement with those of severe infantile sialidosis. The only important exception was that alpha-neuraminidase in the patient's lymphocytes showed normal activity but abnormal pH dependence toward 4-methylumbellyferyl substrate. In addition, a severely damaged kidney suggested that his case may be classified as a unique type of severe infantile sialidosis (possible nephrosialidosis). These observations stress the importance of careful biochemical diagnosis of a case with GM1-gangliosidosis type 1 phenotype.
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A case of odontogenic myxofibroma involving the angle of the mandible is reported. This case arose in the area closely associated with the pericoronal portion of the embedded third molar. When the mandible resected was histopathologically examined, the tumor mass containing various shapes of epithelial cell nests and amorphous calcified bodies in the myxomatous fibrous tissue was found to be formed in the localized area well-demarcated by the enamel of the embedded tooth. These findings strongly suggest that this lesion is of odontogenic origin.