TSH-treatment of thyroid slices increases the amount of DNA released from nuclei by mild DNase-I digestion.
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Biomedical subjects
Publications and source records attributed to Y Abe.
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A water-in-oil-water (W/O/W) multiple phase emulsion was prepared by a two-step emulsification procedure. The oil phase consisted of paraffin oil and sorbitan monooleate. The inner aqueous phase and the outer aqueous phase were 0.5% glucose solution and 3% polysorbate 80 solution, respectively. Viscosity measurements were carried out on the W/O/W emulsion after diluting it with a number of solutions. A given sequence for the solutes that would increase the emulsion viscosity after dilution was determined. This sequence was identical with that obtained with the solutes in an independent permeability experiment using a planar membrane composed of sorbitan monooleate alone. As a result, it was suggested that solutes as well as water can permeate the oil layer of vesicles of the emulsion to change the vesicle volume, thereby causing a change in the emulsion viscosity.
18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and 18F-2-fluoro-2-deoxy-D-mannose (18F-FDM) were tested as tumor diagnostic agents in a transplantable rat tumor and rabbit tumors. Tissue distribution studies in rats showed high tumor uptakes of both radiopharmaceuticals. The tumor uptake reached 2.65 +/- 0.61% dose 18 dose F-FDG/g and 2.65 +/- 0.81% dose 18F-FDM/g at 60 min and remained relatively constant until 120 min. Blood clearance both 18F-FDG and 18F-FDM was very rapid and tumor-to-blood ratios reached 22.1 and 29.4 at 60 min, respectively. Tumor-to-tissue ratios of both radiopharmaceuticals were very high in most organs, especially in the liver, kidney, and pancreas. Positron emission tomography (PET) of rabbit tumor with 18F-FDM clearly delineated the main tumor, central necrosis, and lymph node metastases. These data suggested that 18F-FDM, which is a by-product of 18F-FDG synthesis was also an excellent cancer diagnostic agent as well as 18F-FDG. This is not only a new feature of 18F-FDM, but also an economical improvement on cancer diagnosis by PET.
Pregnant mice were treated with cytosine arabinoside on days 13.5 and 14.5 of pregnancy. Brains of the offspring were studied histologically. The matrix layer of the embryonic brains was extensively destroyed 12 h after the injection of cytosine arabinoside, but regenerated partially on day 17 of gestation. In the cerebral cortex of 1-, 3-, and 5-day-old treated mice, abnormal clusters of young neurons were found on the surface of the developing cerebral cortex. Some clusters still had a supply of immature neurons from the remnants of the regenerated matrix layer. After 20 days, the clusters became gradually indistinct, although some vestigial groups of neurons were observed even after 120 days. In the hippocampus of young mice, the pyramidal cells decreased in number and were disarranged. Heterotopic pyramidal cell masses were found in the stratum radiatum and in the molecular layer of the dentate gyrus. Apical dendrites of pyramidal cells exhibited abnormal arborization. It was demonstrated by 3H-thymidine autoradiography that young neurons in the abnormal clusters in the cerebral cortex were those produced in the matrix layer regenerated after the destructive change by cytosine arabinoside.
Postoperative long-term cancer chemotherapy (PLCC) with a combination of Mitomycin-C, Tegafur and PSK (an immunostimulant) was applied to non-curatively resected cases with stage IV gastric cancer (invading the adjacent organs and/or with metastasis to the liver, peritoneum, and/or distant lymph nodes). This approach has a significant life-prolongation effect. The two-year survival rate was 16.8 per cent in the PLCC group, such being higher than 6.7 per cent and 1.7 per cent in MMC and no chemotherapy groups (p less than 0.05). 50 per cent survival periods in those with liver metastasis were 8.3 months in the PLCC group, such being longer than 5.2 and 2.8 months in MMC and no chemotherapy groups (p less than 0.002) respectively. Combination therapy of PLCC and intra-arterial infusion of 5-FU through the proper hepatic artery prescribed for 8 patients with liver metastasis resulted in a 3-month prolongation of 50 per cent survival periods, compared with PLCC alone (p less than 0.05). In those with peritoneal dissemination the rate was 10.5 months in the PLCC group, that is longer than 6.5 months in the MMC group (p less than 0.02). In cases of invasion to other organs plus distant lymph node metastasis, the time was 11.0 in PLCC and 7.0 months in MMC groups (p less than 0.05). Thus, PLCC is a palliative approach for non-curatively resected carcinoma of the stomach.
In attempts to predict the recurrence of gastric cancer, postoperative changes in serum carcinoembryonic antigen (CEA) levels are monitored in our clinic by radioimmunoassay (Dainabot, Japan). Recurrences are suspected when serum CEA levels are 4 ng/ml, in the postoperative period. Out of 34 patients in whom there were increases in serum CEA, 18 were confirmed to have a recurrence and 15 of these 18 patients were assessed accurately by serial postoperative levels of CEA, two patients died of a recurrence after elevation of serum CEA levels. Thus, recurrence was predicted in 17 out of 34 patients (50 per cent) and in 12 out of 17 patients there was a metastasis to the liver. In 14 out of 34 patients there are no signs of recurrence 9 to 25 months after serum CEA elevations.
Insulin-like action of monovalent monomeric concanavalin A (m-Con A) was examined in rat adipocytes in the presence of anti-m-Con A antiserum. The antisera from rabbits injected with m-Con A reacted with not only monovalent monomeric but also tetravalent tetrameric concanavalin A (alpha-Con A) in Ouchterlony double diffusion analysis. m-Con A alone did not show any appreciable effect on glucose oxidation of adipocytes while it slightly inhibited glycerol release stimulated by epinephrine. In contrast, exposure of adipocytes to m-Con A in the presence of antibodies to m-Con A resulted in stimulation of glucose oxidation and inhibition of epinephrine-stimulated lipolysis. The stimulation and the inhibition with m-Con A in the presence of the antibodies were of the same degree as those with alpha-Con A. Both alpha- and m-Con A were slightly active in inhibiting 125I-labeled insulin binding. These results demonstrate that the ability of anti-m-Con A antiserum to aggregate m-Con A bound to receptors on the isolated-adipocyte plasma membrane allowed m-Con A to mimic the biological activity of insulin and that the aggregation of receptors for ligands other than insulin can induce insulin-like action in rat fat cells.
The virulence of Escherichia coli strains in ascending urinary-tract infection was studied in mice drinking a 5% glucose solution; factors determining the virulence were examined. Of 33 strains, 8 (group I) infected the bladder and kidney, 10 (group II) infected only the bladder, while the remaining 15 strains (group III) did not cause infection. The adherence of group-I and group-II strains to bladder epithelial cells in vitro was inhibited by D-mannose. In group III, 13 strains barely adhered to the epithelial cells, while two strains showed an adherence unaffected by D-mannose. Most strains in groups I and II agglutinated erythrocytes of guinea-pig, chicken, and horse, and cells of Candida albicans in a mannose-sensitive manner. All strains in groups I and II had fimbriae. Virulence for the urinary tract was not directly related with O-serotype, intraperitoneal virulence, ability to grow in mouse urine, ability to ferment dulcitol, production of haemolysin, susceptibility to serum bactericidal activity, or susceptibility to antibiotics. These results suggest that the adherence of the E. coli to mouse-bladder epithelial cells in a mannose-sensitive manner plays an important role in the development of urinary-tract infection in mice and that the adherence is probably mediated by type-1 or closely related fimbriae.
Little is known about the mechanisms of action of polypeptide hormones on chromatin structure and nuclear function. We have employed micrococcal nuclease to examine the effect of TSH on the accessibility of DNA in thyroid nuclei. Brief digestion of nuclear suspensions with 0.05-0.2 U/ml micrococcal nuclease at 26-28 C decreased their opacity at 600 nm. The decrease in opacity was linear with increasing nuclear concentration up to 0.2 mg/ml DNA. This response to nuclease was enhanced in nuclear suspensions prepared from thyroid slices that had been incubated with TSH (50 mU/ml) for 5 h (P less than 0.001). To determine whether TSH also increased the digestion of DNA, we measured the amount of DNA released into 1200 X g supernatants by nuclease treatment of nuclei prepared from control and TSH-treated slices. When TSH-treated nuclei (110 micrograms/100 microliters) were digested with 0.2 U micrococcal nuclease/ml at 37 C for 30 sec, a mean of 12.6 micrograms +/- 3.6 (SD) DNA appeared in the supernatant, as compared to 8.4 micrograms +/- 1.98 DNA from control nuclei (P less than 0.05). This increase in the insensitivity of nuclear DNA to micrococcal nuclease may reflect some conformational change in chromatin in response to TSH. Since micrococcal nuclease sensitivity may reflect transcriptional competence of DNA, we speculate that polypeptide hormones may enhance the accessibility of DNA to RNA polymerase or to endogenous stimulators of transcription.
Thirty-three cases, comprizing 5 of mitral regurgitation (MR), 11 of mitral stenosis (MS), 11 of aortic regurgitation (AR) and 6 of AR and mitral steno-regurgitation (MSR), underwent both preoperative and postoperative heart catheterization in association with a muscle exercise test. Comparisons were made between preoperative and postoperative clinical symptoms, hemodynamics and cardiac functions. The following results were obtained: 1) Improvements in clinical symptoms and hemodynamics at rest were observed in all but two patients. 2) Abnormalities in hemodynamics were obtained after the muscle exercise test, even in cases exhibiting normal hemodynamics at rest. 3) An increase in pulmonary artery mean pressure was noted in MR and MS groups after the muscle exercise test. 4) The cardiac function index values in both the MR and MS groups showed lower levels than those in both the AR and AR + MSR groups. 5) The presence of atrial fibrillation and extent of myocardial fibrosis were related to improvements in postoperative cardiac functions.
In anesthetized sheep, ventilated by positive pressure, pulmonary arterial and left atrial pressures, cardiac output, and lung lymph flow (Qlym) were measured and lymph-to-plasma protein concentration ratio (L/P) was determined. For sheep were irradiated with 60Co on the bilateral lower lobes, avoiding irradiation on the heart and the caudal mediastinal lymph node. Qlym increased during and after irradiation, and reached a new steady state (160% increase), while pulmonary arterial or left atrial pressure did not change. In 4 control experiments, pulmonary hemodynamics, Qlym or L/P did not change. Therefore the increased fluid or protein flux after irradiation cannot be ascribed only to abnormal pulmonary hemodynamics. Endothelial damages seem to play a role in the increase of fluid filtration and protein permeability.
The present experiment was designed to clarify the contribution of the renin-angiotensin system to the acute depressor action of angiotensin I converting enzyme inhibitor and also to assess the role of the kidney under such conditions. In anesthetized dogs, intrarenal and i.v. infusion of SQ 14,225 at a rate of 0.5 mg/min resulted in a significant and similar fall in systemic blood pressure. This effect was not altered even when the receptors were occupied by exogenous angiotensin II (100 ng/min i.v.) This would suggest that the renin-angiotensin system plays a relatively minor role in the blood pressure reduction in normotensive anesthetized dogs. Six hours after nephrectomy when the plasma renin activity had become negligible, SQ 14, 225 produced a significant fall in systemic blood pressure. The magnitude was not statistically different from that noted during i.v. infusion of SQ 14,225 in the dog with both kidneys intact. The effect was abolished after inhibition of kallikrein, as induced by aprotinin (10,000 kallikrein inhibitory unit/kg i.v., 10,000 kallikrein inhibitory unit/kg.hr i.v.). In light of these findings, the possibility that the extrarenal kallikreinkinin system contributes to the acute hypotensive action of SQ 14,225 rather than to the inhibition of the metabolism of angiotensin has to be given attention.
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Thirty-five children with previously untreated ALL or AUL who received CNS prophylactic therapy with 8 treatment regiments were analyzed. After eutering complete remission, patients received CNS-prophylaxis with one of the following regimens: Group A- cyclic high dose multichemotherapy plus intermittent intrathecal methotrexate (MTX); Group B-craniospinal irradiation plus intermittent intrathecal MTX; Group C-intermittent high dose intravenous MTX. Incidence of CNS-leukemia and bone marrow relapse was less frequent in Group B. EEG abnormalities were seen in 38.5% of Group A, 40% of Group B, and 28.6% of Group C respectively, but the abnormalities were transient. IQs of three groups were above 100, but IQs of CNS-leukemia patients, especially VIQs had a tendency to be low.