[Clinical significance of the shape of isodose curves in intracavitary radiation therapy of carcinoma of the uterine cervix].
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Biomedical subjects
Publications and source records attributed to T Higuchi.
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Oxytocin neurons of the paraventricular nucleus were identified by their antidromic response to stimulation of the neurohypophysis and a short high-frequency burst of spikes displayed before reflex milk ejection in the urethane-anesthetized lactating rat. During suckling, the milk ejection-related bursts recurred at regular intervals. Stimulation of the neurohypophysis at 50-300 pulses/s for 0.5-6 s (current 1 mA) evoked additional burst(s) with the amplitude higher than those of spontaneously occurring ones. Stimulation with subthreshold current for antidromic response or constant-collision test could also facilitate the neurosecretory bursts. Possibly, oxytocin released within the magnocellular nuclei is responsible for these effects.
The promoting effect of N-acyl derivatives of a collagen peptide which was fractionated from the hydrolysates of collagen on the rectal absorption of sodium ampicillin was studied. An increase in the blood level of ampicillin was observed in rabbits and rats following the administration of a sodium ampicillin suppository containing N-octanoyl(C8-CP), decanoyl(C10-CP), dodecanoyl(C12-CP), and stearoyl(C18-CP) derivatives of collagen peptide. The most efficient action was observed in the suppository containing C18-CP. Some factors influencing the promoting effect of the adjuvants on the rectal absorption of sodium ampicillin from solution were also studied in rats using in situ perfusion method and loop method. The promoting effect of the adjuvants on the rectal absorption of sodium ampicillin was markedly increased in the hypertonic solution. The promoting effect was also suppressed by the addition of calcium chloride to the solution administered to the rectal loop or to the perfusate in the in situ perfusion method. These results suggest that the tight junction of the epithelia of the rectum will be markedly influenced by the presence of the adjuvants, especially in the hypertonic solution. The adjuvant interaction with the calcium ions located in the rectal membrane may be involved in the enhanced absorption of sodium ampicillin.
The energy metabolism of living tumors in rats and hamsters were investigated by obtaining in vivo 31P-NMR spectra, and the effects of chemotherapy on tumors were evaluated by observing the changes of these spectra. Tumor cells of rat glioma, human glioblastoma and human neuroblastoma were inoculated subcutaneously in the lumbar region of the animals. After the tumor grew to over 1.5 cm in diameter, in vivo 31P-NMR spectrum data was obtained selectively from the tumor with a TMR-32 spectrometer (Oxford Research Systems, U.K.). Several peaks (ATP, inorganic phosphate (Pi), phosphodiesters and phosphomonoesters (PME) were observed in the tumors. The heights of these peaks varied widely corresponding to the tumor growth. However, the spectrum pattern of each tumor in an active stage was found to be essentially the same regardless of histological type or tumor origin. The phosphocreatine (PCr) peak was small, ATP and PME peaks were large and tissue pH calculated from the chemical shift of Pi was low in each tumor group. After intravenous injection of a large dose of a chemotherapeutic agent, ATP peaks decreased and the Pi peak increased gradually, resulting in a dominant Pi peak pattern after several hours in all groups. With lower drug doses, spectrum changes were temporarily seen in the tumors. These findings indicated that drugs with a high dose have a selective and a direct action on the energy metabolism of tumor tissues. In vivo 31P-NMR spectra measurement is very valuable not only to investigate the energy metabolism in tumor tissue but also to evaluate the effects of chemotherapy on the tumor.
A case of ossified tumor in the anterior abdominal wall that proved to be a metastatic transitional cell carcinoma of the bladder is reported. Computerized tomography detected dense calcification within the tumor but it did not differentiate ossification from calcification. A soft x-ray roentgenogram of the resected tumor revealed a fine trabecular pattern of the ossified area.
The present study indicates that in kindled rats there are no differences in the total number or affinity of the binding sites in the temporal cortex and a slight increase in the total number of binding sites in the cortex when compared with controls. These results, in view of our other observations, suggest that in the kindled rat brain there may be an increased release of SRIF but no down-regulation of SRIF receptors in the temporal cortex and cortex. There appears to be a significant decrease in the number of SRIF receptors in kindled hippocampus. The mechanism by which this occurs remains unclear.
Lymphatic uptake of sodium cefoxitin after injection into rectal connective tissue was greater than after injection into the femoral muscle of rats. Coadministration with sodium 5-methoxysalicylate enhanced lymphatic drug uptake at both sites. This enhancement may be an indirect result of 5-methoxysalicylate's suppression of vascular permeation of the cefoxitin. An adjuvant-induced increase in lymphatic fluid flow may also be partially involved in the enhancement of cefoxitin lymphatic transport.
Rectal absorption of insulin by depancreatized dogs was significantly enhanced by the coadministration of enamine as a suppository adjuvant and if this was followed by a further suppository containing enamine alone, the insulin absorption was even further enhanced. The additional enamine suppository resulted in high serum insulin concentrations for a longer time and effected a significant decrease in serum glucose concentrations. To decrease serum glucose concentrations effectively in depancreatized dogs, serum insulin levels had to remain high for a long period of time, rather than be transient.
Sodium salicylate, disodium ethylenediaminetetraacetic acid (EDTA) and polyoxyethylene-23-lauryl ether (POE) significantly enhanced the absorption of cefoxitin from the rectum but with the following differences. The effectiveness of salicylate or EDTA was enhanced by sodium chloride, whereas the activity of POE was not. Although the ratios of plasma cefoxitin peak values to cefoxitin dose were constant with POE or EDTA, the peak to dose ratios with salicylate decreased with increasing cefoxitin concentration. Phlorizin and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) inhibited the effectiveness of salicylate, but did not influence the adjuvant action of either POE or EDTA. Although treatment with salicylate resulted in slightly less protein release than treatment with NaCl, both POE and EDTA increased the release of protein from the rectal mucosa. It appears that the effects of salicylate occur at the protein fraction of the rectal mucosa through a saturable process whereas the adjuvant action of POE and EDTA appears to involve some irreversible disruption of the membrane.
4-Ethoxy-3-methoxyphenylglycerol-gamma-formyl ester (compound IV) was identified as a degradation product of both 4-ethoxy-3-methoxyphenylglycerol-beta-syringaldehyde ether (compound I) and 4-ethoxy-3-methoxyphenylglycerol-beta-2,6-dimethoxyphenyl ether (compound II) by a ligninolytic culture of Coriolus versicolor. An isotopic experiment with a C-labeled compound (compound II') indicated that the formyl group of compound IV was derived from the beta-phenoxyl group of beta-O-4 dimer as an aromatic ring cleavage fragment. However, compound IV was not formed from 4-ethoxy-3-methoxyphenylglycerol-beta-guaiacyl ether (compound III). gamma-Formyl arylglycerol (compound IV) could be a precursor of 4-ethoxy-3-methoxyphenylglycerol (compound VI), because 3-(4-ethoxy-3-methoxyphenyl)-1-formyloxy propane (compound VII) was cleaved to give 3-(4-ethoxy-3-methoxyphenyl)-1-propanol (compound VIII) by C. versicolor. 4-Ethoxy-3-methoxyphenylglycerol-beta,gamma-cyclic carbonate (compound V), previously found as a degradation product of compound III by Phanerochaete chrysosporium (T. Umezawa, and T. Higuchi, FEBS Lett., 25:123-126, 1985), was also identified from the cultures with compound I, II, and III and degraded to give the arylglycerol (compound VI). An isotopic experiment with C-labeled compounds II' and III' indicated that the carbonate carbon of compound V was derived from the beta-phenoxyl groups of beta-O-4 substructure.
Energy dispersive X-ray analysis was performed on the renal tubular cells of two patients with inorganic mercury intoxication. Some lysosomes of these cells consisted of unusual matrices of aggregated electron-dense grains which were positive for mercury, selenium and sulphur. Though maps of the specific X-rays of both mercury and selenium coincided exactly with these lysosomes, the molecular ratio of selenium to mercury ranged between zero and 2.9. It is unlikely that the trace element of selenium and exogenous inorganic mercury are deposited in the lysosomes independent of each other, but rather their coexistence in the characteristic lysosomes strongly suggests a compound formed by binding mercury to the SeH residues of selenoprotein.
The identity of a sulfate ester in rat milk has been determined to be N-acetylneuramin lactose sulfate. This sulfate ester is present in rat mammary tissue and in human milk. The presence of this compound offers an explanation for the simultaneous delivery of sulfate and calcium via the milk, two essential nutrients in early life, without precipitation of calcium sulfate in the milk. N-acetylneuramin lactose sulfate is hydrolyzed in the gut of the neonate and absorbed as inorganic sulfate. This is the first report suggesting that this ester may be of nutritional importance.
The effects of microelectrophoretic applications of neurotransmitter substances and their antagonists on the activity of paraventricular oxytocinergic neurones were studied in urethane anesthetized lactating rats. Oxytocinergic neurones were identified by their antidromic response to the stimulation of the neurohypophysis and by their characteristic high frequency discharge of action potentials approximately 15-20s before reflex milk ejection. Acetylcholine (ACh) excited the majority (75%) of paraventricular oxytocinergic neurones, and none of the cells was inhibited in its activity by ACh. In about half of the oxytocinergic cells, atropine and hexamethonium reduced the number of action potentials during the burst discharge preceding reflex milk ejection. Noradrenaline (NE), dopamine (DA) and serotonin (5-HT) reduced the activity of most (75-100%) of oxytocinergic neurones, and none of the cells was excited by these catecholamines. These results suggest that paraventricular oxytocinergic neurones receive excitatory cholinergic inputs and inhibitory noradrenergic, dopaminergic and serotonergic inputs.
A technique for indirect measurement of blood pressure by a combination of commercially available apparatuses was devised. There were good correlations in both of systolic and diastolic blood pressures measured by the indirect and direct methods.
A highly sensitive and specific radioimmunoassay (RIA) for oxytocin was developed and used to measure oxytocin concentrations during both suckling and parturition in individual rats. In urethane-anaesthetized rats, the suckling stimuli, provided by ten pups, induced intermittent increases in intramammary pressure of about 10 mmHg. This was associated with a significant (P less than 0.01) increase in serum oxytocin levels from 19.5 +/- 4.5 (S.E.M., n = 9) to 49.1 +/- 7.4 pmol/l (n = 9) in the samples taken within 30 s from the time of the peak in the pressure. These rises in serum oxytocin returned rapidly to the basal levels as expected from the short half-life (1.46 min) of oxytocin in general circulation. On day 22 or 23 of gestation, serum oxytocin levels remained stable until 0-0.5 h before the first fetus was expelled. They then increased significantly (P less than 0.01) from 27.6 +/- 4.6 pmol/l (n = 19) in samples taken 0-0.5 h before to 45.1 +/- 5.6 pmol/l in samples taken after the expulsion of the first fetus and gradually increased until the last fetus was expelled. Serum oxytocin concentrations then declined but remained higher than those observed before the first fetus had been born until at least 1-1.5 h after the expulsion of the last fetus. Thus, this oxytocin RIA revealed increased concentrations of the hormone in blood during both suckling and parturition in the rat.
Developmental changes in levels of oxytocin in the blood and the pituitary gland and in oxytocin responses to oxytocin-releasing stimuli were investigated in the rat from the fetus close to term to the 40-day-old young adult. The oxytocin content of the pituitary gland rose gradually from fetuses of 21 days of gestation to 40-day-old rats. Pituitary oxytocin levels expressed in terms of body weight also increased up to day 25 after birth and declined slightly thereafter. In contrast, serum concentrations of oxytocin increased from day 21 of pregnancy up to day 5 after birth but were stable thereafter. Oxytocin levels in both blood and the pituitary gland were equal in 23-day-old fetuses and 1-day-old infants born on day 22 of pregnancy. There was no difference in serum and pituitary oxytocin levels in newborn pups and unborn littermates of day 22 or 23 of gestation. The i.p. injection of hypertonic saline induced a significant increase in serum oxytocin levels on day 5 and later, but no effect in the fetus on day 22 of gestation and in the 1-day-old infant. The responsiveness to the osmotic stimuli increased after 5 days of age. The i.p. injection of diethyldithiocarbamate, a noradrenaline synthesis inhibitor, or phenobarbitone was effective in raising blood oxytocin levels only in rats older than 10 and 20 days of age respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
The chronic toxicity of a new topical glucocorticoid, difluprednate (DFBA) was studied in Beagle dogs. DFBA ointment (0.05%) was percutaneously treated to the back of dogs at daily doses of 125, 12.5 and 1.25 micrograms/kg for 6 months. The local effects of DFBA In the treated area, thinning of the skin and inhibition of the fur-growth were observed with scale and erythema. The skin showed histological atrophy of the epidermis, a decrease of the adipose tissue and atrophy of the adnexa. These changes returned to normal after the 2-month withdrawal period. The systemic effects of DFBA In the 125 micrograms/kg group, the following changes were observed, although neither death nor severe symptoms occurred: General observations were seen an increase of water intake and urinary volume. A decrease of lymphocytes and eosinophils, and an increase of neutrophils were observed in the hematological examination. There were high sodium and low potassium levels, and an increase of alkaline phosphatase and gamma-glutamyltranspeptidase activities in the biochemical examination. The organ weights showed a decrease of the thymus, adrenals, prostate and ovaries, and an increase of the liver and kidney. An atrophy of the lymphatic tissues and adrenal cortex, retardation of the sexual maturation, glycogen deposit in the hepatic cells, slight degeneration of the renal tubuli, and slight thinning of the sternum and non-treated skin were noted in the pathological examination. These changes returned to normal after the 2-month withdrawal period. In the 12.5 micrograms/kg group, the atrophic changes in the thymus, adrenal and non-treated skin appeared slight. In the 1.25 micrograms/kg group, no changes were found. Conclusively, all the local and systemic changes observed by DFBA in this study were due to the already known pharmacological effects of glucocorticoids. It is considered that a 12.5 micrograms/kg dosage is similar to a non-effect dose.
Dynamic computerized tomography (CT) was performed on 42 patients with acute head injury to evaluate the hemodynamics and to elucidate the nature of fatal diffuse brain bulk enlargement. Patients were divided into two groups according to the outcome: Group A included 17 nonfatally injured patients, eight with acute epidural hematomas and nine with acute subdural hematomas; Group B included 25 fatally injured patients, 16 with acute subdural hematomas and nine with bilateral brain bulk enlargement. Remarkable brain bulk enlargement could be seen in all fatally injured patients with acute subdural hematoma. In 29 (69%) of 42 patients, dynamic CT was performed within 2 hours after the impact. In the nonfatally injured patients with brain bulk enlargement, dynamic CT scans suggested a hyperemic state. On the other hand, in 17 (68%) of the 25 fatally injured patients, dynamic CT scans revealed a severely ischemic state. In the fatally injured patients with acute subdural hematoma, CT Hounsfield numbers in the enlarged hemisphere (hematoma side) were significantly lower than those of the opposite side (p less than 0.001). Severe diffuse brain damage confirmed by follow-up CT scans and uncontrollable high intracranial pressure were noted in the fatally injured patients. Brain bulk enlargement following head injury originates from acute brain edema and an increase of cerebral blood volume. In cases of fatal head injury, acute brain edema is the more common cause of brain bulk enlargement and occurs more rapidly than is usually thought.