[An experimental study for the improvement on the method of administration of Dotite Calcein for labeling to the hard tissues (author's transl)].
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Biomedical subjects
Publications and source records attributed to H Fukazawa.
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1) Production of tetanus antitoxin in rabbits and monkeys was followed by passive hemagglutination (HA) and toxin-neutralization (TN) tests. The HA activity was observed in both IgM and IgG in both animal species. 2) In rabbits, IgM antitoxin was detected as early as in 7 days, reached the maximum titer in 10--14 days, and disappeared in 3 weeks after the primary immunization. Antitoxin of IgG class was detected in 10 days, and increased gradually. The ratio of HA/TN titers ("serum ratio") was high at an early stage of primary immunization and approached the unity in 3--4 weeks. Unlike the case of guinea pigs, IgM was found to contribute greatly to this high level of ratio. Besides, most rabbits produced IgG antitoxin of high ratios at early stages of immunization. 3) The immune response of monkeys showed a pattern very similar to that of rabbits except a few days' delay in the time course of antitoxin titers. No IgG antitoxin with a high serum ratio was demonstrated. Therefore, the high serum ratio of early sera could be accounted for mainly by IgM. 4) In response to the secondary immunization, no IgM antitoxin was detected in either animal species. 5) No definite correlation between serum ratio and avidity in terms of "dilution ratio" was demonstrated. However, both the dilution ratio and serum ratio were high at an early stage of immunization and gradually decreased, though the magnitudes of the ratios were variable depending on individual animals.
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Two cases of nevoid basal cell carcinoma syndrome were reported with a review of pertinent literature. The first case was a 59-year-old man, whose autopsy was warranted. Signs and symptoms manifested in this case were basal cell carcinoma, generalized multiple nevi, multiple cysts in the jaws and long bones, pits in the palm and sole, frontal and occipital bossing, ossification of the falx cerebri, a bifid rib, renal fibroma and a patent foramen ovale. The family history revealed a hereditary predisposition as to the syndrome. The patient in the second case included basal cell carcinoma, multiple nevi, multiple jaw cysts, pits in the palm and sole, frontal bossing, calcification of the falx cerebri, cervical vertebral fusion and high-arched palate.
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Since 1979, we have performed multidisciplinary treatment using intensive immunotherapy with biologic response modifiers (BRM) in combination with surgical treatment of oral cancer. Chemotherapy and radiotherapy were also included as part of the therapy. A historic control study was performed. Adjuvant therapy was administered by standardized methods, and the distribution of patients at various stages was similar between groups. The immunotherapy group showed a shorter treatment period, lower rates of recurrence, metastases, and side effects, greater histologic effects at the end of the first treatment, and a higher survival rate than the nonimmunotherapy group. Immunologically, immunotherapy tended to promote positive immune reactions and inhibit negative immune reactions.
A relatively simple and sensitive high-performance liquid chromatographic (HPLC) method is described for measuring galocitabine (Ro 09-1390) and its meatbolites, i.e. 5'-deoxy-fluorocytidine (5'-DFCR), 5'-deoxy-fluorouridine (5'-DFUR) and 5-fluorouracil (5-FU), in blood for the purpose of studying pharmacokinetics and toxicokinetics in small animals. The procedure for blood includes deproteinization with acetonitrile. Blood components were separated on a reversed-phase C18 column with a linear gradient of acetonitrile and water and detected at a wavelength of 270 nm. The between-day relative standard deviation (RSD) was less than 10% for all compounds at concentrations of 10-100 micrograms ml-1. The calibration curves obtained from the analysis of blood samples were linear and the correlation coefficients ranged from 0.997 to 0.999. The calculated determination limits were 6.9 micrograms ml-1 for galocitabine, 3.0 micrograms ml-1 for 5'-DFCR, 4.0 micrograms ml-1 for 5'-DFUR and 3.7 micrograms ml-1 for 5-FU.
Two brothers with congenital myotonic dystrophy also had cystinuria with large renal stones. This report is the first to document the concurrence of cystinuria and congenital myotonic dystrophy. It is uncertain whether these two conditions are coincidental or share a common pathogenesis.
Beer was subjected to five successive chromatographic procedures to isolate the gastrin release-inducing activity, guided by bioassay of the fractions in anaesthetized Donryu rats. The procedures were: (1) hydrophobic interaction chromatography (aqueous effluent with an HP20 column); (2) weak cation-exchange chromatography (1 M acetic acid eluate with a CM Sephadex C-25 column); (3) gel filtration (methanol eluate with a Sephadex LH-20 column); (4) same as (2); (5) high-performance liquid chromatography (YMC-Pack ODS-AM with 7% acetonitrile-0.01 M HCl). The active component finally isolated had a specific activity approximately 10000 times higher than that of beer. It was identified by means of mass, 1H- and 13C-nuclear magnetic resonance spectral analyses as N-methyltyramine (NMT). The dose of NMT giving maximal gastrin-releasing activity was 25 microg/kg, and the 50% effective dose was approximately 10 microg/kg on oral administration to rats. NMT was isolated and identified as a gastrin release inducer in beer. Its concentration in beer is sufficient to account for most of the activity of beer.
A heparin coated cardiopulmonary bypass system was evaluated for canine veno-venous extracorporeal membrane oxygenation (ECMO). The ECMO system consisted of a hollow fiber membrane oxygenator and pediatric centrifugal pump but no reservoir. In Group 1 (N = 6), the ECMO system was coated with a covalent, heparin-binding method, except for the centrifugal pump, and animals underwent ECMO without systemic heparinization. In Group 2 (N = 4), the same system without the heparin coating was used under full heparinization. During 12 hours of ECMO with a bypass flow of 500 ml/min, there were no significant differences in gas exchange or blood trauma between the two groups. There was no apparent macroscopic thrombus formation in either group. In addition, it was suggested that Group 1 had less activation of platelets on the blood-contacting surfaces compared with Group 2. This ECMO system, with simplified circuits using a centrifugal pump, showed efficient gas exchange and antithrombogenicity when coated with heparin using a covalent binding method comparable to the non heparin coated system requiring systemic heparinization.
After oral administration of bromazepam, 50 mg/kg/day for 14-28 days to rats, the rate of elimination of the unchanged drug from the blood increased by 20-40%, as determined from the half-lives of the blood decay curves during the first 4 hr after administration of an oral or intravenous test dose of bromazepam. During the chronic administration, the liver weight increased 30-40%, with concomitant enlargement of the liver. The hepatomegaly was associated with elevation of microsomal drug-metabolizing enzyme activities, including that responsible for the oxidation of bromazepam itself. Spectral characteristics of the isolated microsomes indicated that the manner by which bromazepam caused the elevation (induction) of the enzyme activities was of the "phenobarbital type" rather than the "methylcholanthrene type." Since certain steps of bromazepam metabolism take place in the liver, it appears reasonable to assume that the increase in the elimination rate found after chronic administration may depend upon the enhanced drug-metabolizing activities in the liver. The hepatomegaly and the associated elevation of enzyme activities returned to the normal states within 7 days after withdrawal of the drug. Neither the increase in the elimination rate nor the enzyme induction was observed with doses lower than 5 mg/kg.
A leukocyte extract, which had a high peroxidase activity (mostly myeloperoxidase), converted tenoxicam [4-hydroxy-N-(2'-pyridyl)-2-methyl-2H-thieno-(2,3e)-1,2-thiazine-3 - carboxamide-1,1-dioxide] a potent antiinflammatory drug, into four novel metabolites in the presence of H2O2: 4,5-dihydro-4-oxo-5-methyliminopyrido (1,2a) imidazole (metabolite I), 2-carboxyl-3-thiofenesulfinic acid (metabolite II), 2-carboxyl-3-thiofenesulfonic acid (metabolite III), and N-methyl-N'-(2-pyridyl)oxamide (metabolite IV). These metabolites were probably formed by a one-electron oxidation reaction at the center carbon atom of the beta-diketone moiety of tenoxicam. Tenoxicam is a cofactor for the reduction of peroxidases and this capability may explain at least a part of the antiinflammatory effect of tenoxicam.
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Specificities of several known protein kinase inhibitors were evaluated using an assay system in which activities of protein kinase A, protein kinase C, protein tyrosine kinase and calmodulin-dependent protein kinase III were simultaneously detected. Inhibitory spectra of H-89, K252a, H-7, staurosporine, tyrphostin and herbimycin A observed in the assay system were similar to those reported in the purified protein kinase assay systems. It was also found that KN-62 selectively inhibited calmodulin-dependent protein kinase III activity. These data suggest that the assay system may be effective and practicable in evaluating specificities and screening of new protein kinase inhibitors.