[Spectral investigations of structures of 1,3-diketoneisoniazid hydrazone derivatives].
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Biomedical subjects
Publications and source records attributed to T Sakaguchi.
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The intraocular pressure responses in living rabbit and enucleated human eyes during tonography, suction-cup and bulbar pressure tests were continuously recorded by closed electric manometry. The tonography tests in rabbits produced an initial rapid rise in pressure, followed by a slight decline during tonography and a sharp drop to a level lower than the initial pressure as soon as tonography was discontinued; recovery to the initial pressure level was gradual. Increasing the plunger weights made the responses more marked. Enucleated human eyes showed similar results except, of course, there was no recovery to the initial pressure level. Similar pressure responses were produced in the suction cup and bulbar pressure tests. Our data showed that the manometric curves in living rabbit and enucleated human eyes during compression are of the same type.
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Jc1:SD rats were given methylnitrosourea (MNU; 5 mg/kg, IP) on day 13 of gestation. Male offspring with MNU-induced microcephaly were examined on the Biel water maze and its mirror-image maze at 6 weeks of age and on a radial eight-arm maze at 14 weeks of age. The MNU rats showed postnatal depression in body weight. Their brain weight was about 60% of the control value, and they were thus microcephalic. The MNU animals made significantly more errors on the Biel maze and its mirror-image maze than the controls. In the radial arm maze test, they required more trials to acquire the learning criterion than the controls, and the animals with the acquired learning criterion were fewer. In the retest, however, no significant difference appeared in number of trials required for reacquisition of the criterion between the MNU and control animals. The autopsy of the MNU animals revealed the thinned cerebral cortex and hypoplastic hippocampus. The present results with the MNU rats confirmed the learning impairment and suggested no effect of microcephaly on retention of the acquired memory.
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Epidermal growth factor receptor (EGFR) protein overexpression is commonly found in human gastric cancer, and its gene amplification is known to correlate with poor prognosis in gastric cancer patients. With regard to therapy trials targeting EGFR, it has been reported that stable transfection of EGFR antisense or treatment with antibody against EGFR results in growth suppression of human cancer cells that express high levels of EGFR. We have designed an adenovirus-expressing antisense EGFR and have investigated its effect on the growth of gastric cancer in vitro and in vivo. Following infection with EGFR antisense RNA-expressing adenovirus (Ad-EAS), the cell surface EGFR protein levels of infected cancer cells were markedly reduced, and the in vitro growth of Ad-EAS-infected cells was significantly inhibited relative to control-infected cells in all three gastric cancer cell lines (AGS, KKLS, and MKN28) studied here (P < .0002). In a nude mouse subcutaneous tumor system, in vivo tumor growth of MKN28 was significantly inhibited after Ad-EAS treatment, and inhibition on day 48 was 93% by volume compared with that of untreated controls. These results suggest that an adenoviral vector system targeting the down-regulation of EGFR could be a good candidate for the therapy of gastric cancers that overexpress EGFR.
Toxicologic studies indicate that cefotaxime is well tolerated by animals. It is difficult to demonstrate acute toxicity. Subacute and chronic effects include local reactions at the site of injection, some hematologic changes with enlargement of the spleen, cecal enlargement in rats and mice, and slight changes in kidney tubules. Special studies indicate that the potential for nephrotoxicity in animals is minimal, and limited clinical reports show no nephrotoxicity in humans. In animals cefotaxime is well tolerated when combined with furosemide, gentamicin, lidocaine, or probenecid. Intrathecal or suboccipital injections of cefotaxime produce convulsions. At concentrations studied cefotaxime was not mutagenic, and no effects on fertility or teratology were observed in animals.