[Statistics on prosthetic restorations VI].
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Biomedical subjects
Publications and source records attributed to S Noguchi.
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The effects of truncal vagotomy after administration of N-methyl-N'-nitro-N-nitrosoguanidine on the incidence and number of gastric carcinomas and gastric acid secretion, gastrin secretion, antral pH, and duodenal reflux were investigated in inbred Wistar rats. Rats were subjected to truncal vagotomy after N-methyl-N'-nitro-N-nitrosoguanidine treatment. Vagotomy significantly increased the incidence and number of adenocarcinomas of the glandular stomach. It also resulted in significantly more atypical glandular hyperplasias, which are precursors of gastric cancer. Furthermore, it caused a decrease in gastric secretion and an increase in mucosal pH in the antrum but did not increase duodenal reflux. These findings indicate that vagotomy has a promoting effect on the development of gastric cancers. The reduced gastric acid secretion, but not duodenal reflux, may be related to this increased incidence of gastric cancer.
Fifty-seven patients with low-grade and low-stage urinary bladder cancer were treated at our University Hospital between 1970 and 1980. The incidence of low grade and low stage cases was higher in the young group than in the older group, and in male than in female (p less than 0.05). Most of the patients were well-controlled by either TUR or other conservative therapies. The 5-year relative survival rate was 113%. The 5-year actual cumulative recurrence rate after TUR was 63%, whereas, the 5-year actual cumulative recurrence rate was only 35.4% in those who received intravesical instillation therapy and 25% in those who undergone RCH (Radio-Chemo-Hyperthermia) therapy. Five patients (9%) showed an increase of tumor grade from low to intermediate at the time of intravesical recurrence, but no patient showed a change from low to high grade.
The mechanism of estrogen enhancement in the growth of androgen-dependent Shionogi carcinoma 115 (SC115) maintained in castrated DS mice by low doses of androgen (10 micrograms of testosterone propionate or 4 micrograms of 5 alpha-dihydrotestosterone/mouse/day) is reported. Although the low androgen treatment slightly but significantly (P less than 0.05) stimulated tumor growth, concomitant estrogen (4 micrograms of 17 beta-estradiol/mouse/day) significantly (P less than 0.01) enhanced the tumor growth. The high growth rate, histological type (medullary carcinoma), androgen dependency, and high androgen receptor content of the tumor grown during estrogen plus low androgen treatment did not differ significantly from those of the original SC115 tumor grown in normal males or in castrated mice treated with high doses of androgen. On the other hand, the treatment with low doses of androgen alone induced the development of slowly growing spindle-shaped cells from the medullary SC115 cells. The spindle-shaped cells containing low levels of androgen receptor were shown to be androgen independent and were also induced from the SC115 cells in nontreated castrated mice. These findings demonstrated that low doses of androgen and estrogen synergize to maintain and increase the growth of SC115 cells, whereas low doses of androgen alone fail to maintain the SC115 cells.
It was generally accepted for 20 yr that the growth of Shionogi carcinoma 115 (SC115) is stimulated only by androgen. In the present study, the growth-stimulative effect of estrogen alone on SC115 tumors was examined in castrated mice. Daily injections of physiological doses of 17 beta-estradiol did not enhance the tumor growth. However, high doses of 17 beta-estradiol (10-100 micrograms/mouse/day) significantly stimulated the growth of tumors in a dose-dependent manner. Since high doses of diethylstilbestrol (10-50 micrograms/mouse/day), which does not bind to androgen receptor, could markedly stimulate the growth of tumors and since antiandrogen (cyproterone acetate) failed to inhibit the growth stimulation induced by high doses of 17 beta-estradiol, it is concluded that high doses of 17 beta-estradiol, which binds to androgen receptor with relatively low but significant affinity, enhance the tumor growth not via the androgen receptor system. The growth speed, histological type, content, and affinity of androgen, estrogen, and progesterone receptors and pattern of newly synthesized proteins labeled in vitro with [35S]methionine of tumors grown by high doses of estrogen were not significantly different from those of the original SC115 tumors grown in normal males. Furthermore, seed tumors from one to six generations grown by pharmacological doses of estrogen alone could rapidly grow only in normal males and not in castrated males. The present findings demonstrate that the growth of SC115 tumors in vivo is stimulated by physiological doses of androgen or pharmacological doses of estrogen.
A procedure was developed for obtaining both cytologic and histologic specimens from patients suspected of having hepatic malignancy at the time of ultrasonically guided liver aspiration biopsy using a 22-gauge needle of 0.4 mm inner diameter. The fine needle and the syringe used were heparinized before use to avoid blood coagulation in the materials obtained. With heparinized needle and syringe it was possible to centrifuge the materials obtained and make good smears containing abundant tumor cells, and to obtain small tissue specimens. Histologic specimens obtained with the heparinized needle were fixed in 2.5% glutaraldehyde, postfixed in 1.0% osmium tetroxide, and embedded in epoxy Epon resin. Ultrathin sections were made and usually stained with Azan-Mallory stain. In 41 patients suspected of having hepatic malignancy, a correct diagnosis was made by a combination of these examinations. The sensitivity of this procedure for hepatic malignancy was 100%, and the specificity was 95.7%. Therefore, this procedure is a very reliable method for diagnosis of hepatic malignancy.
Recently, many studies have drawn attention to the possibility of imaging estrogen-receptor-positive breast cancer with a high-affinity ligand such as 17 beta-(16 alpha-[125I]iodo)-estradiol (I-E2). We tried to determine the most suitable time and dose for imaging with this compound, using uteri of mature Sprague-Dawley rats. Although the uptake of I-E2 in the target organ (uterus) reached its peak 1 h after subcutaneous injection, the ratio of uptake in the target organ to that in nontarget organs (lung and muscle) peaked at 4 h. We also found that this ratio decreased as the dose increased. The clearest image was available 4 h after the dose meeting the minimum requirement for imaging was administered. An imaging trial of dimethylbenzanthracene (DMBA)-induced mammary carcinoma is also demonstrated.
The phototoxicity of acridine orange and argon laser irradiation on Walker carcinosarcoma 256 stomach tumors was studied. Wistar strain rats bearing stomach tumors 4-6 mm in diameter 5-10 days after their implantation were injected intraperitoneally with 40 mg/kg of acridine orange 2 hr before irradiation. Then the forestomach was opened and the tumors were exposed to the argon laser at 488 nm at an intensity of 15 mW/cm2 for 20 min. Tumors in rats treated with acridine orange were brightly fluorescent during irradiation. No marked temperature rise was detected during irradiation. Argon irradiation significantly prolonged the survival of rats treated with acridine orange. Histologically, complete or partial tumor necrosis was observed, with sparing of surrounding mucosa, in rats treated by the combination therapy. Phase-contrast and electron microscopy showed that cytotoxicity was mediated by changes in the cell, nuclear and lysosomal membranes. Neither the dye nor laser alone had any effect.
Protein alterations during the development of the mouse brain were studied by two-dimensional gel electrophoresis. A protein spot with a molecular weight (MW) of 68,000 and pI value of 5.6 was found in the brain of the 11th day of gestation. Between the 12th and the 14th day of gestation, spots with the same MW and lower pI values appeared progressively. Neuraminidase digestion converted the pI of these acidic spots to 5.6. Thus, increased sialylation appeared to occur during this period. This class of molecules became hardly detectable on the 15th day, and disappeared completely after the 16th day. Analogous spots were present in the heart, liver, and stomach of the embryos, although the increased sialylation was not observed in the liver. No adult organs so far examined showed these spots. On the other hand, two polypeptides (MW 55,000, pI 4.7, and 53,000, pI 4.6) appeared in the brain on the 13th day of gestation and persisted throughout the fetal period. After birth, they became hardly detectable. Furthermore, a spot (MW 48,000, pI 4.8) became newly detectable in the brain 4-5 weeks after the birth.
Five cases of adenomatous goiter have been studied by an electron microscope using an immuno-reaction for thyroglobulin (TG) and focusing on the mechanism of endocytosis. Positive stain for TG was demonstrated in follicular lumina, large reabsorbed colloid droplets and small subapical vesicles. Endocytotic vesicles ranging from 320 nm to 1600 nm in diameter were observed in the cytoplasm as pits in the apical plasma membrane. Some of them showed direct connection with the positive stain for TG in the follicular lumen and the others were completely ingested in the cytoplasm. With statistic analysis, a majority of the vesicles showing the positive stain for TG in the cytoplasm distributed in the range of 200 nm to 1200 nm in diameter with the peak in 300 nm to 399 nm and was situated within an extent of the diameter measured from the endocytotic vesicles. Engulfment of colloid by pseudopods and fusion of the reabsorbed colloid droplets were encountered as extremely rare findings and appeared to play no major role for formation of large colloid droplets in adenomatous goiter.
A case of nonfunctioning parathyroid carcinoma in a 69-year-old female has been studied by light and electron microscopy. The tumor, located on the left side of the anterior neck, was well encapsulated by connective tissue but showed invasion to the capsule and to the thyroid. The tumor cells exhibited a trabecular arrangement surrounded by capillary networks but focally showed several ductal structures. They were polygonal in shape, had a large nucleus showing frequent mitosis and poor cytoplasm containing glycogen. Some tumor cells had clear and abundant cytoplasm, and resembled water-clear cells of the parathyroid. Immunohistochemically, no thyroglobulin was demonstrated in the tumor tissue. Electronmicroscopically, the tumor cells with high N/C ratio contained poorly developed cell organelles and abundant glycogen particles. They were poor in secretory granules and had no conglomeration of lipid. Desmosomes and tonofibrils were observed. The ratio of the reported number of nonfunctioning parathyroid carcinoma to that of functioning one in Japan was compared with that in western countries. No difference of the ratio was found between these two, when identical criteria were employed.
Ultrastructural localization of human thyroid peroxidase in normal and hyperfunctioning states has been studied. Peroxidase activity was visualized ultrastructurally with a cytochemical reaction using 0.05% diaminobenzidine-tetrahydrochloride, and hydrogen peroxide with a final concentration of 0.0025%, 0.005%, or 0.01%, respectively, and 2% osmium tetroxide. Reaction product demonstrating the enzyme was clearly observed in cell organelles with a final concentration of hydrogen peroxide at 0.0025% or 0.005%. In the normal portion of thyroid, follicular cells demonstrated the reaction product, located mainly in rough-surfaced endoplasmic reticulum and perinuclear cisternae and in addition a small amount of the product was found in Golgi cisternae and small vesicles dispersed throughout the subapical cytoplasm. The reaction product significantly increased in amount in the cell organelles described above and in addition, a characteristic heavy deposition of the product was observed at the external surface of the microvilli in the follicular cells of thyroid obtained from the patients with treated Basedow's disease.
Carcinoembryonic antigen (CEA) and elastase 1 in the serum were determined by enzyme immunoassay and radioimmunoassay, respectively, in 224 healthy subjects, 49 patients with pancreatitis, 53 patients with pancreatic carcinoma and 129 patients with cancer in other organs. The CEA concentrations in the serum were significantly higher in patients with pancreatic carcinoma than in those with pancreatitis, but this concentration was not a satisfactory indicator of pancreatic carcinoma localised to allow irradication by resection as it was raised in only 47% of the patients. High CEA concentrations were also slightly, but not significantly, more frequent in patients with cancer of the pancreatic body or tail, and unresectable cancer or cancer of more than 6.0 cm in longest diameter than in those with cancer of the pancreatic head, resectable cancer or cancer of less than 6.0 cm diameter. Serum elastase 1 was raised in only 42% of the patients with pancreatic carcinoma and could not be used to distinguish patients with pancreatic carcinoma from those with pancreatitis. In contrast with CEA, however, its concentration was abnormally high significantly more frequently in patients with cancer of less than 6.0 cm in longest diameter than in those with larger tumours. It was also raised slightly, but not significantly, more frequently in those with cancer of the pancreatic head and in patients with resectable cancer than in those with unresectable cancer. A combination of these two tests raised the diagnostic rate of pancreatic carcinoma to 77% without a remarkable decrease in the specificity for pancreatic carcinoma. In particular, it raised the diagnostic rates of cases of cancer of the pancreatic head, resectable cancer and cancers of less than 3.0 cm and 3.0-6.0 cm in longest diameter. Therefore, a combination of measurements of CEA and elastase 1 in the serum is very useful for early detection of pancreatic carcinoma.
The diagnostic accuracy of measurement of carcinoembryonic antigen (CEA) and of analysis of the cytological characteristics of pericardial fluid was assessed in 10 patients with benign pericarditis and 7 patients with malignant pericarditis. The mean CEA levels of pericardial fluid specimens from patients with malignant pericarditis were significantly higher than those from patients with benign pericarditis. However, a high CEA level was not seen in a specimen of pericardial fluid which contained nonepithelial tumor cells. Positive cytological findings were obtained in specimens of pericardial fluid from 85.7% of the patients with malignant pericarditis. Correct diagnosis of malignancy was made by CEA assay alone or by cytological examination alone in 85.7% of the patients examined, while a combination of these methods raised the diagnostic rate to 100%.
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