[Studies on binding sites of epidermal growth factor in rat gastric mucosa].
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Biomedical subjects
Publications and source records attributed to K Kawamoto.
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Activities of cathepsin B, cathepsin L, and plasminogen activators (urinary type plasminogen activator and tissue type plasminogen activator) were assayed in homogenates of cancer tissue, normal tissue closely surrounding the cancer tissue, and normal tissue distant from the cancer tissue from 30 patients undergoing surgery for gastric cancers and 10 patients undergoing surgery for colon cancers. Activities of those proteases were also assayed in homogenates of adenoma tissue from 10 patients undergoing polypectomy for colon polyps. In the gastric cancer tissue homogenates, the activities of cathepsin B, cathepsin L and tissue type plasminogen activator were significantly higher than in normal tissues. By contrast, the activities of urinary type plasminogen activator of gastric cancer tissues were significantly lower than normal tissues. In the colon cancer tissue homogenates, the activities of cathepsin, B, cathepsin L, and urinary type plasminogen activator were significantly higher than in normal tissues. On the other hand, the activities of tissue type plasminogen activator of cancer tissues were significantly lower than normal tissues. But there were no significant differences in the activities of plasminogen activators between the cancer tissues and adenoma tissues. These results suggest that cathepsin B and cathepsin L play an important role in gastric and colon cancer proliferation and evolution, although the roles of plasminogen activators in gastric and colon cancer proliferation and evolution and in the colon adenoma-carcinoma sequence are still unknown.
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In making a decision for death, it is well said that brain stem electroencephalogram (EEG) could be an important index. We applied Ishida's nasopharyngeal lead to animals (canine), normal healthy men and patients with brain dysfunction. In normal healthy men, the nasopharyngeal lead revealed clear brain waves. Additionally, we tried a photic stimulation in all the models and a gradual removal of the cerebrum in canines to investigate whether interaction between Ishida's nasopharyngeal lead and the cortical electroencephalogram exists. Furthermore, whenever there was a chance, we examined instances with brain dysfunction by the method, and confirmed that brain waves obtained from Ishida's nasopharyngeal lead were derived from the skull base.
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With the aid of flow cytometry (FCM), distribution of DNA content in 40 cases of brain tumour, primary culture cell, and secondary culture cell can be determined and chronological change after subculture is studied from the analysis of their cell cycle. In most primary cultures, proliferating index (PI) is likely to decrease, which suggests that environmental change might affect the growth activity. In comparison with that of the original sample, DNA-histogram of the secondary culture can be divided into the following 3 types: the type recovering to the original pattern ("adapting type"), in which astrocytoma, ependymoma, glioblastoma and medulloblastoma are included, 2) the type increasing more at G2 + M phase than the original ("proliferating type"), in which meningioma and some of glioblastoma are included, and 3) the type decreasing so far as to induce degeneration or death ("degenerating type"), in which pituitary adenoma and neurinoma are included. FCM is of great usefulness for the study of cell kinetics of a tumour cell undergoing culture and the present method will be available for the respective study of biological characteristics of the cultured cell, established cell line or sensitivity test for antineoplastic agents.
The thickness of Brunner's glands was measured using an ocular micrometer in 297 cases of surgically resected peptic ulcer and in 120 autopsy cases (control group). The mean maximum thickness of Brunner's glands in the control group was 1.55 +/- 0.37mm (mean +/- SD) and no difference in thickness was noted for each decade of age. The mean maximum thickness of Brunner's glands in patients with gastric ulcer, duodenal ulcer and gastroduodenal ulcer was 2.34 +/- 1.06, 3.18 +/- 1.07 and 3.24 +/- 1.05mm, respectively. When an ulcer is within the duodenum, Brunner's glands near the ulcer were thicker than those contralateral to it. In patients with gastric ulcer, Brunner's glands were the thickest in the pyloric ulcer group and negative correlation was noted between the thickness of Brunner's glands and the distance to the ulcer from the pyloric ring. Since gastric acidity is supposed to be lower when an ulcer is located more proximally, these results suggest that Brunner's glands become hyperplastic not only with the presence of an ulcer in the duodenum but also by acid hypersecretion of the stomach.
Though we recently found some reports on sterile sorting of natural killer cells (NK cells) by flow cytometer (FCM), which manifested cytotoxicity, no reports have concerned antineoplasticity of sterile NK cells on glioma cell lines and cultured surgical materials of brain tumor so far as we know. Monocytes were sampled from the peripheral blood of healthy adults, stained with fluorescein isothiocyanate (FITC)-labeled antihuman monoclonal antibodies, and sorted by an FCM, which had been sterilized with 0.5% Hibitane alcohol solution. Over 95% of the cells obtained were NK cells, and their viability was disclosed to be 97% by the FDA staining. Using thus obtained NK cells, the antineoplastic effects were evaluated in 3 kinds of glioma cell lines and 5 surgical specimens by the microcytotoxicity test. The effects varied widely from 9 to 74% (E/T ratio 40) for glioma cell lines, and from 1 to 66% (E/T ratio 10-40) for surgical specimens. It is expected in the future to apply NK cells clinically using this sterile sorting technique.
The tumor cell kinetics before and after intra-arterial injection of cisplatin (CDDP) was examined in a patient with maxillary carcinoma using flow cytometry and propidium iodide and fluorescein isothiocyanate labeled bromodeoxyuridine double staining. In addition, the viability was determined with fluorescein diacetate and compared with the histological picture. The action mechanism which the authors obtained 24 hours after intra-arterial injection of CDDP to the clinical case was considered to be S phase block, especially early S phase block. Markedly decreased viability also makes us consider the cytocidal effect. These findings correlated with the data of the fundamental investigation reported previously. Histological examination after the intra-arterial injection of CDDP revealed remarkable necrosis in the tissue.
A new hydrolase for conjugated bile acids, tentatively named chenodeoxycholyltaurine hydrolase, was purified to homogeneity from Bacteroides vulgatus. This enzyme hydrolyzed taurine-conjugated bile acids but showed no activity toward glycine conjugates. Among the taurine conjugates, taurochenodeoxycholic acid was most effectively hydrolyzed, tauro-beta-muricholic and ursodeoxycholic acids were moderately well hydrolyzed, and cholic and 7 beta-cholic acids were hardly hydrolyzed, suggesting that this enzyme has a specificity for not only the amino acid moiety but also the steroidal moiety. The molecular weight of the enzyme was estimated to be approximately 140,000 by Sephacryl S-300 gel filtration and the subunit molecular weight of the enzyme was 36,000 by SDS-polyacrylamide gel electrophoresis. The optimum pH was in the range of 5.6 to 6.4. The NH2-terminal amino acid sequence of the enzyme was Met-Glu-Arg-Thr-Ile-Thr-Ile-Gln-Gln-Ile-Lys-Asp-Ala-Ala-Gln. The enzyme was activated by dithiothreitol, but inhibited by sulfhydryl inhibitors, p-hydroxymercuribenzoate, N-ethylmaleimide, and dithiodipyridine.
NADH-dependent vitamin K reductase activity in rat liver microsomes was measured by detecting the amount of the reduced form of vitamin K from the oxidized form of the vitamin. The enzyme activity was not detected when intact microsomes were employed as the enzyme source, but the solubilization of the microsomal enzyme with 1.5% Triton X-100 caused a development of the activity. Although the enzyme activity decreased gradually with time after the solubilization, the enzyme was stabilized by the addition of 20% glycerol and 2 mM vitamin C. Some optimal assay conditions for the vitamin K reductase were determined using the solubilized enzyme, and the standard assay method is described. Vitamin K reductase activity was not affected by warfarin and N-ethylmaleimide (NEM), but pyridoxal-5-phosphate (PAL-P) inhibited the activity, especially when microsomes were preincubated with PAL-P. The enzyme activity was not inhibited by N-methyltetrazolethiol (NMTT) and NMTT-containing antibiotics, suggesting that the hypoprothrombinemia caused by beta-lactam antibiotics was not due to the inhibition of NADH-dependent vitamin K reductase.
Pineal parenchymal tumors are so rare that their responses to radiation and/or chemotherapy are not well known. Two cases of pineocytoma, which responded well to radiation therapy and chemotherapy, are reported. A 45-year-old female received radiation therapy in a total dose of 5000 rads to the tumor. Three months after the completion of therapy, computed tomography (CT) showed complete disappearance of the tumor, and she remains well as of 1 year after treatment. The second patient, a 6-year-old girl, underwent four cycles of intravenous infusion of ACNU (25 mg) over 10 months. CT demonstrated complete disappearance of the tumor and, 18 months post-operatively, there was no evidence of tumor recurrence. The results in these two cases indicate that postoperative radiation therapy and/or chemotherapy should be strongly considered for patients with pineal parenchymal tumors.
We studied the healing of acetic acid-induced esophageal ulcers in rats with respect to the cellular kinetics. Esophageal ulcers were induced by topical application of acetic acid to the serosal surface. Well-demarcated circular or elliptical ulcers had developed by day 3 after the acid treatment. These ulcers began to decrease in size from day 7 and had healed by day 14. Histological and cellular kinetic findings, with bromodeoxyuridine (BrdU), were degeneration of the esophageal mucosa on day 1 and ulcer formation on day 3, with an increase in the number of BrdU-labeled cells in the esophageal mucosa around the ulcer. On day 7, regenerated epithelium was found to extend towards the ulcer base and the regenerated epithelium had become thicker, with papilla formation, by day 10. On day 14, the ulcer base was covered with thickened regenerated mucosa, with a decrease in the number of BrdU-labeled cells. Marked proliferative activity of the regenerated mucosa and thickening of the esophageal mucosa, with papilla formation, were observed during the healing process.
A single s.c. injection of diethyldithiocarbamate (DDC, 1 g/kg) induced not only gastric but also duodenal mucosal damage in rats. DDC induced marked decreases in gastric acid output, gastro-duodenal mucosal blood flow and transmucosal potential difference prior to the development of mucosal lesions. Superoxide dismutase activity in the gastro-duodenal mucosa was also inhibited, while catalase and glutathione peroxidase activities gradually increased after the administration of DDC. These results suggest that a decrease in mucosal defensive mechanisms plays an important role in the development of DDC-induced gastro-duodenal mucosal damage and that oxygen-derived free radicals may also participate in the development of this mucosal damage.
The inter-island variations and biological population affinity were examined for the Cook islanders in terms of non-parametric dental characters. The materials used in the present study consisted of plaster casts for 397 people, ages 4-20, collected on Rarotonga, Mangaia and Pukapuka in the Cook Islands. The dental characters observed were 15 traits on the teeth crown. The samples have been divided into five population series on the basis of their native islands: Pukapuka, N-S group (northern-southern island crossbreedings), Rarotonga, Mangaia, and S group (southern islands except Rarotonga and Mangaia). For comparison with other ethnic populations, the samples excluding the Pukapuka are combined into one group to represent full-blood southern-Cook Island Polynesians and named "Southern Cook" here. There were no significant sex differences in the incidences of dental traits in the data used in this study, so they were combined for the statistics. A cluster analysis was carried out to compare inter-population affinities on the basis of Smith's Mean Measure of Divergence (MMD) using the frequencies of shovelling, Carabelli's cusp, protostylid, cusp 6, cusp 7, and deflecting wrinkle. The results are briefly summarized as follows: 1. The differences between the Pukapukans and other four groups in the Cook Islands were observed in the case of 11 characters. Within the samples of the four island groups making up Southern Cook, there were no definitive population differences in dental morphology. The cluster analysis based on Smith's MMD values emerged as two main clusters in the Cook Islands: one cluster consisted only of the Pukapukans, and the other consisted of the rest. The latter was divided into two subclusters. 2. The frequencies of shovelling in the Southern Cook (23%) were quite similar at the medium level (S + S.S), to those in other Polynesian groups as well as in the Micronesian groups. The Pukapukans, however, gave a fairly low percentage (10%). 3. The two populations from the Southern Cook and Pukapuka were compared with other Oceanic populations. The incidences of double shovelling were similar to those of the Guamese, but lower than those of the Hawaiians. The Carabelli's cusp, protostylid and cusp 6 showed higher frequencies than those in the Hawaiians and Guamese. On the other hand, the interstitial tubercle showed a lower percentage than those in the Hawaiians and Guamese. As far as the incidence of the deflecting wrinkle are concerned, the Southern Cook, together with the Guamese, were intermediate between the Hawaiians and Pukapukans.(ABSTRACT TRUNCATED AT 400 WORDS)
Diethyldithiocarbamate (DDC), which markedly lowers activity of Cu, Zn-superoxide dismutase (SOD), induces not only gastric but also duodenal mucosal damage in rats. In this experiment, we studied on the mechanisms of DDC-induced duodenal mucosal damage with special reference to aggressive and defensive factors. Possible importance of oxygen-derived free radicals was also investigated. Male Wistar rats weighing about 200 g received a single subcutaneous injection of DDC at a dose of 1 g/kg. Mucosal lesions such as edema, shortness of villi and shallow erosion developed from 3 hours after DDC injection. The ulcer index reached at its maximum 12 hours later. Gastric acid output was markedly inhibited from 87.7 +/- 8.7 to 14.0 +/- 2.6 microEq/kg/h (m +/- SE) 30 minutes after the administration of DDC (p less than 0.01), which gradually recovered thereafter. Duodenal mucosal blood flow before DDC injection was 144.7 +/- 12.7 ml/min/100 g, which decreased to 83.3 +/- 5.1 (p less than 0.01) 1 hour later. Transmucosal potential difference of the duodenum before DDC injection was -9.5 +/- 1.0 mV, which decreased to -3.8 +/- 1.3 (p less than 0.05) 30 minutes later. Duodenal alkaline secretion before DDC injection was 15.6 +/- 0.8 microEq/kg/h, which decreased to 5.0 +/- 0.9 microEq/kg/h (p less than 0.01) 90 minutes later. PAS-stained mucus of Brunner's glands remained unchanged by the administration of DDC. SOD activity was markedly inhibited from 57.7 +/- 4.0 to 15.7 +/- 0.9 u/mg protein 3 hours after the administration of DDC (p less than 0.01), then recovered 24 hours later.(ABSTRACT TRUNCATED AT 250 WORDS)
We examined the antitumor effect of recombinant human lymphotoxin (rHuLT) on a xenotransplantable human malignant glioma line. Tumor-bearing nude mice were treated with rHuLT for three weeks following four schedules: intratumoral injection of rHuLT 20,000 units once a week, twice a week, intravenous injection once a week and twice a week. The inhibition rate of tumor growth was 98.8%, 99.1%, 92.1% and 98.8%, respectively. Histologically, necrotic lesions were observed in the tumors of all treated mice. Thrombo-obstructive changes of tumor vessels were also seen in the tumors of mice after intravenous injection of rHuLT. None of the mice died as a result of this treatment in spite of significant body weight loss. These results indicate that rHuLT has a strong antitumor effect on a xenotransplantable human malignant glioma line.
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