[Physiologic and pharmacologic effects of arachidonic metabolites on the menstrual cycle and perinatal physiology].
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Biomedical subjects
Publications and source records attributed to N Mitsuhashi.
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The record of 73 patients with 153 sites of bone metastases from a lung cancer treated by radiation have been reviewed to evaluate the effectiveness of pain relief. Radiation therapy for bone metastases was found to be very effective. Sufficient symptomatic improvement was achieved in 94% of all patients, while 63% obtained almost complete pain relief that was sustained until death. Onset of a symptomatic response to radiotherapy was within less than 20 Gy in total dose in more than 80% of all patients. There were no significant differences in the frequency of pain relief among the various histological types of primary lung tumors.
To determine if IMACIS-1 might have the capability of specifically pinpointing an adenocarcinoma in the human lung, xenografts of adenocarcinomatous nude mice that were injected with IMACIS-1 have been evaluated by scintigraphy, and the IMACIS-1 biodistribution in the tissue measured after sacrifice. Results have revealed that scintigraphic images obtained twenty-four hours after the IMACIS-1 injection showed some activity in the area of the tumor. At seventy-two hours after the IMACIS-1 injection, tumoral radioactivity was only seen in mice with a large tumor. At ninety-two hours after injection, the animals were sacrificed and a biodistribution study was performed. The IMACIS-1 uptake was expressed in counts per minute per gram of tissue. The tissue-to-blood uptake ratio in mice with a large tumor was 8.4 in the viable part of the tumor, 27.2 in the necrotic part of the tumor, 3.0 in the liver, and 1.5 in the spleen, respectively. In contrast, the ratio in mice with a small tumor was 3.4 in the viable part and 18.3 in the necrotic part. Immunoperoxidase staining with either the anti CEA or the anti CA 19-9 antibody was strongly visible in the necrotic part of the tumor.
Patients with multiple primary malignant tumors involving a primary lung cancer have been analyzed at our department in the Gunma University hospital. With reference to the lung cancer, three quarters of these patients were clinically in stages III or IV. The lung cancers were histologically classified into 26 epidermoid cancers, 14 adenocarcinomas, one large cell carcinoma, and one small cell carcinoma. Other primary cancers were 13 gastric cancers, 7 laryngeal cancers, 6 cervical cancers, 3 colon cancers, and other such cancers. Cases manifesting simultaneous cancers showing less than a one-year interval were 15 whereas 27 cases had double primary cancers with intervals of over one-year. Eleven patients had been given radiation therapy for their initial malignant tumor, but only two cases were considered to have incurred a radiation-induced lung cancer with a latent period of 5 and 12 years respectively.
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It was reported that unsaturated long chain fatty acids, such as arachidonic acid, oleic acid and docosahexaenoic acid inhibit the binding between progesterone and estrogen receptors and steroid hormones. Most of the long chain fatty acids are contained in phospholipids within the cells. The effect of phospholipids on the binding between R5020 and progesterone receptors was studied. Phosphatidyl ethanolamine and sphingomyelin had no effect on binding, but phosphatidyl inositol and phosphatidyl serine inhibited the binding 53% and 34% respectively. The effect of phosphatidyl inositol on the binding between R5020 and progesterone receptors was dose dependent. Scatchard analysis revealed that the addition of phospholipid markedly decreased the number of binding sites from 1398 fmol/mgp to 258 fmol/mgp, but the dissociation constant was little affected.
Phospholipids such as phosphatidyl inositol and phosphatidyl serine inhibit the binding of R5020 and progestin receptors. The effect of phospholipids on the binding of estrogen and estrogen receptors of rat uterine cytosol was studied. Phosphatidyl choline, sphingomyelin, phosphatidyl inositol, phosphatidyl ethanolamine, cardiolipin, and phosphatidic acid inhibited the binding of estradiol and estrogen receptors. This inhibitory effect of phosphatidyl inositol and cardiolipin was dose dependent.
Unsaturated long chain fatty acids are known to inhibit the binding between estrogen and estrogen receptor, or progesterone and progesterone receptor in rat uterus. The effects of long chain fatty acids on the binding between androgen receptor of castrated rat prostate and 3H-R1881 were studied. The binding was not affected by saturated fatty acids such as palmitic acid (16:0) or stearic acid (18:0). But unsaturated fatty acids such as oleic acid (18:1), arachidonic acid (20:4) and docosahexaenoic acid (22:6) inhibited the binding between androgen receptor and 3H-R1881. The inhibitory effect of arachidonic acid was dose dependent. Scatchard analysis showed that the addition of arachidonic acid markedly decrease the number of binding sites of androgen receptor. But the dissociation constant was not affected. The inhibitory effect of arachidonic was not a competitive one.
The present status of clinical application and future prospect of immunotherapy using BRMs, especially PS-K, for cancer patients treated by irradiation were described here. Prolonged survivals were revealed in the radiation therapy of patients with carcinoma of lung and uterine cervix concomitant use of PS-K. And the condition necessary for long-term survival with BRMs were thought to be that the tumor was almost disappeared by irradiation. But, there is not an evaluation criteria for BRMs without any direct effects on tumor. Then judgment of clinical usefulness of immunopotentiators are difficult and needs to make new evaluation criteria.
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In an attempt to learn how nonsteroidal factors modulate brain progestin and glucocorticoid receptors, the effects of saturated and unsaturated fatty acids, and phosphatidylinositol on the binding of [3H]R5020 or [3H]dexamethasone, determined by sucrose density gradient and gel filtration on LH20, were examined in the cerebral cortical cytosol from 10-day-old female rats which contain a considerable amount of progestin and glucocorticoid receptors. Unsaturated fatty acids such as oleic (C18:1), arachidonic (C20:4) and docosahexaenoic acid (C22:4) depressed the [3H]R5020 or [3H]dexamethasone binding in increasing order, but saturated fatty acids had no effect. Arachidonic and docosahexaenoic acids, which were strong inhibitors, lowered the binding dose dependently. The fatty acid inhibition on brain progestin and glucocorticoid receptors was thus a function of acid dose and degree of acid unsaturation. Interestingly, prostaglandin D2 did not show any effect. Among phospholipids tested the inhibitory effect of phosphatidylinositol on the [3H]R5020 binding was evident, but no significant effect was found with phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine or sphingomyelin. The phosphatidylinositol inhibition was dose dependent. Analysis on kinetics and Scatchard plot have revealed the noncompetitive type of inhibition by arachidonic acid and phosphatidylinositol. From these results it is suggested that the unsaturated nonestrified fatty acid, arachidonic acid, and phosphoinositides modulate the brain progestin and, possibly, glucocorticoid receptors through their binding at sites different from steroid binding sites on the respective receptor molecules.
The specific binding of R5020 to the 7S cortical progestin receptors was markedly inhibited by unsaturated long chain fatty acids, such as oleic acid, arachidonic acid, and docosahexaenoic acid. The inhibitory effect of docosahexaenoic acid was dose-dependent in the range of 1.5 X 10(-6) M to 1.5 X 10(-4) M.
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Long chain fatty acids were known to interfere with the binding between rat uterine estrogen receptors and estradiol. The effect of long chain fatty acids on the binding between rat progesterone receptors and 3H-R5020 was studied. The binding was inhibited by palmitic acid, palmitooleic acid, arachidonic acid and docosahexaenoic acid. Docosahexaenoic acid was the strongest inhibitor and palmitic acid was the weakest inhibitor. The inhibitory effect of palmitic acid and arachidonic acid was dose dependent. In rat uterine cytosols, there existed an arachidonic acid binding factor which was distinct from progesterone receptor. The inhibitory mechanisms of long chain fatty acids was not clear, but the inhibitory effect was stronger if the number of carbon atoms increased with the number of double bonds.
In order to study prostanoid biosynthesis, pregnant myometrium was taken from eleven patients undergoing cesarean section. Homogenates of myometrium were incubated with 14C labelled arachidonic acid and biosynthetic products were studied using silicic acid column chromatography, thin layer chromatography and gas-liquid chromatography. There were two metabolites assumed to be 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) or hydroxy acid. Concerning the prostaglandins, pregnant myometrium produced 6-keto PGF1 alpha, PGF2 alpha and PGE2. But the conversion rates to each prostaglandin has no relation to the gestational week. Moreover, the conversion rate to each prostaglandin was not higher in the samples taken from the patients with pains than that from the patients with no pains. The total conversion rate to prostaglandins also has no relation to the gestational week or pains. However the PGE2/PGF2 alpha (p less than 0.001) and 6-keto PGF1 alpha/PGF2 alpha (p less than 0.05) ratios were significantly higher in the patients with pains.
The relation between the CT findings and the histopathology of metastatic liver tumors was investigated in nine autopsy cases of liver metastases. In hypervascular and necrotic tumors, large necrotic lesions demonstrated by CT were almost consistent with the pathological findings, but small metastatic nodules were better identified on plain CT than those on contrast-enhanced CT. Postmortem CT examination of the liver obscured metastatic nodules as compared with diagnostic CT. Diffuse liver involvement of lymphoma cannot be identified on CT examination. Plain CT is considered to be useful for screening liver metastases.
A growth factor which stimulates DNA synthesis in resting mouse Balb/c 3T3 cells (3T3 cells) has been extracted from human follicular ovaries and partially purified. The dialyzed cytosol stimulated 3H-DNA synthesis in 3T3 cells dose-relatedly. When the extract was subjected to salting-out procedures with ammonium sulfate, there was found a 60% saturation cut containing growth promoting activity. Ion exchange on a cation exchanger of the active 60% cut produced an active fraction in the 1M NaCl elute. Gel filtration of ovarian cytosol yielded an active fraction that eluted between chymotrypsin (25,000 MW) and cytochrome C (12,400 MW). The data presented here indicate the presence of an endogenous growth factor in human ovary. The factor appears to be a basic protein, heat-labile and soluble in 40% or less ammonium sulfate, with a molecular weight of between 12,400-25,000. With respect to the biochemical characteristics, this growth factor is quite similar to the porcine ovarian growth factor previously reported.