[Radiation therapy of brain tumors metastatic from bronchogenic carcinoma].
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Adenocarcinoma↗
Biomedical subjects
K Tsutsui
Publications and source records attributed to K Tsutsui.
The nuclear scaffold exhibits DNA-binding sites selective for supercoiled DNA.
Binding of exogenous DNA to the nuclear scaffold was investigated using a plasmid DNA (pBR322, EcoRI site deleted) of various topological forms and nuclear subfractions with different levels of nuclear DNA depletion. When supercoiled DNA was incubated with histone-depleted nuclei (nuclear halo), a dose-dependent binding of the DNA occurred, whereas no binding was observed with relaxed and linear forms of DNA. The bound DNA was released upon linearization with BamHI or digestion of the scaffolding structure with proteinase K. Extensive digestion of the halo with micrococcal nuclease generated additional sites which bind both relaxed and linear DNA. In the presence of a large excess of calf thymus DNA, these sites were effectively blocked and the specificity to supercoiled DNA was restored. The binding of all forms of DNA was abolished by heat-denatured DNA. There was no detectable change in linking number of the scaffold-associated supercoils. Competitive binding was observed between supercoiled DNAs with unrelated sequences, indicating that no specific nucleotide sequence is required for the binding. RNA was found to be a weak competitor. A DNA binding assay performed on electrophoretic blots of solubilized nuclear scaffold revealed a protein component with apparent molecular weight of 120,000 which retained selective binding to supercoils. These results suggest that the nuclear scaffold possesses DNA-binding sites for torsionally strained domains of chromatin and that an integral protein factor is involved in the binding. Implications of the findings are discussed in connection with proposed functions of the nuclear scaffold and topoisomerase II.
Animals↗
Treatment results of intracranial germinoma as a function of the irradiated volume.
Between 1962 and 1986, 70 patients were treated with radiation for confirmed or suspected intracranial germinoma at our hospital. The diagnosis was based on histology in 30 cases, cerebrospinal fluid (CSF) cytology in 12 cases, and on clinical and radiological findings in the remaining 28 cases. The target of radiation was the primary tumor site in 34 cases (Group A), the entire neuraxis in 22 cases (Group B), the whole brain in 4 cases (Group C), and the ventricle plus spine in 6 cases (Group D). Four patients were not included in the above groups for various reasons. The average radiation dose was 50-55 Gy to the tumor, 30 Gy to the whole brain, and 24 Gy to the spinal axis. The 5- and 10-year survival rates of the 68 primary cases in which radiotherapy was completed were 86% and 79%, respectively. The survival and relapse-free survival rates for the above 4 groups did not differ significantly, although slightly better results were seen in Groups B and C. Five cases in Groups A and D developed intracranial recurrence, 4 adjacent to the primary site but 1 distant from it, whereas no intracranial recurrence was found in the whole-brain-treated groups (B and C). One patient in Group B developed spinal metastasis, which was possibly due to inadequate radiation fields, and another in Group B developed abdominal metastasis via the shunt tube. Craniospinal irradiation should be administered to the patients with demonstrated meningeal seeding or with a positive CSF cytology. For cytology-negative cases with no evident metastasis, irradiation of the tumor plus a wide margin is usually sufficient, but craniospinal irradiation should be considered when the disease extends along the ventricular walls or is present in both pineal and suprasellar regions.
Adolescent↗
Effects of photoperiod and temperature on the binding of follicle-stimulating hormone (FSH) to testicular preparations and plasma FSH concentration in the Djungarian hamster, Phodopus sungorus.
The effects of artificial photoperiod and temperature on testicular FSH binding and plasma FSH levels were studied in adult male Djungarian hamsters. In Exp I, hamsters were transferred to long day (LD) photoperiods (16-h light, 8-h dark) after 8 weeks of adaptation in short day (SD) photoperiods (8-h light, 16-h dark), but the ambient temperature was maintained at 25 C throughout the experiments. A marked increase in the total FSH binding per two testes occurred between 10 and 47 days after transfer to LD, a change that was accompanied by testicular growth. Binding of FSH per testicular weight decreased during the same period. Scatchard plot analyses of the parameters indicated that LD decreased both the concentration of FSH binding sites and the equilibrium dissociation constant (Kd). Plasma FSH levels increased between 10 and 47 days after transfer to LD. In contrast, when hamsters reared under LD for 12 weeks were transferred to SD (Exp II), FSH binding per unit weight basis increased 19 weeks after transfer to SD, but the total binding per two testes decreased markedly. In Exp III, sexually mature male hamsters were subjected to different ambient temperature and photoperiods. There were no significant effects of different ambient temperatures on the testicular weight and testicular FSH binding in animals exposed for 8 weeks to either LD or SD. However, plasma FSH levels of hamsters maintained at 25 C under LD was significantly higher than FSH levels at 7 C under LD. A similar effect of temperature on plasma FSH levels was observed in hamsters under SD. The present study indicates that photoperiod is a more important environmental factor than temperature for the regulation of FSH receptor in the Djungarian hamster.
Animals↗
Inhibitory effect of Sertoli cell-cultured media on LH binding to mouse Leydig cells in culture.
The aim of this study is to examine the influence of Sertoli cells on LH binding to Leydig cells in culture in immature mice. Leydig cells and Sertoli cells were obtained from the testes of immature C57BL/6Ncrj mice and were cultured in serum-free medium for 7 days. The LH binding to Leydig cells and the FSH binding to Sertoli cells were dependent on incubation time, the number of cells, and the amount of labelled hormone added. The dissociation constant for LH binding to Leydig cells was 7.3 x 10(-10) M. Co-culture of Leydig cells with Sertoli cells for 7 days decreased LH binding to Leydig cells. The binding was 34.9% of that to Leydig cells cultured alone. After cultivation of Leydig cells with spent Sertoli cell-cultured medium (SM) for the last 4 days of the 7-day culture period, LH binding to Leydig cells decreased to as low as 17.4% of that of the controls. For the controls, LH binding was measured in Leydig cells cultured in spent Leydig cell-cultured medium (LM). There was no difference between SM- and LM-cultures in the final survival rate or the percentage of cells showing histochemically demonstrated 3 beta-hydroxysteroid dehydrogenase activity. These data suggest that some factor or factors are secreted from the cultured Sertoli cells and inhibit the binding of LH to Leydig cells in culture.
Animals↗
[Usefulness of MR imaging and I-131 MIBG scintigraphy for the localization of extra-adrenal pheochromocytoma; a case report].
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3-Iodobenzylguanidine↗
[An autopsy case of acute pulmonary hemorrhage in systemic lupus erythematosis].
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Adult↗
Interaction of heme with a synthetic peptide mimicking the putative heme-binding site of histidine-rich glycoprotein.
We synthesized a hexapeptide, Gly-His-His-Pro-His-Gly, previously identified as a tandem motif in the histidine-rich glycoprotein (HRG) which has multiple heme-binding sites. Binding of heme to the peptide was demonstrated by the characteristic difference spectrum showing a close resemblance to that of HRG, implying that the peptide binds heme through biaxial coordination with histidine imidazoles. Furthermore, the EPR spectra of the heme-peptide and heme-HRG complexes were almost completely identical in pattern, showing signals characteristic of the low spin iron. The results suggest that the synthetic peptide simulates the heme-binding properties of HRG and that each tandem motif in HRG serves as a unitary binding site for heme.
Binding Sites↗
Hemin inhibits virion-associated reverse transcriptase of murine leukemia virus.
The virion-associated reverse transcriptase activity of Rauscher murine leukemia virus was inhibited by freshly prepared hemin at a concentration of 10(-4) M. When the hemin solution was aged at room temperature for 5 days, the concentration of 50% inhibition decreased to as low as 10(-7) M. Removal of O2 from the solution partially prevented the aging. The hemin inhibition was reversible and appears to be directed against the enzyme rather than the template. Hemin did not inhibit the activity of reverse transcriptase purified from avian myeloblastosis virus.
Heme↗
Autoradiographic study of binding and internalization of follicle-stimulating hormone in the mouse testis minces in vitro.
The internalization of FSH-receptor complexes was demonstrated in mouse testis by means of light and electron microscopic autoradiography. Chopped testicular pieces were incubated with radioiodinated FSH (131I-NIADDK-rat FSH-I-4) for 10, 20, 60 and 180 min. After incubation the pieces were fixed with glutaraldehyde containing tannic acid, and embedded in Spurr's resin. Semithin and ultrathin sections were cut for light and electron microscopic autoradiography, respectively. In light microscopic autoradiographs, silver grains were preferentially localized over Sertoli cells, regardless of incubation time. Sixty to 70% of the total number of grains were located over Sertoli cells which account for only about 4% of the total cell population of the seminiferous tubules. The majority of these grains correspond to the specific FSH binding sites, because few grains remained after incubation with an excess amount of unlabeled FSH. In electron microscopic autoradiographs, the half-distance (HD) value for the 131I-labeled line source was about 216 nm in the present study. After 10 min of incubation, 56.6% of the total number of silver grains were located over the plasma membrane of Sertoli cells. In testicular pieces incubated for longer periods (20, 60 and 180 min), both the percentage and relative concentration of grains increased in the Golgi apparatus and lysosomes and decreased in the plasma membrane. These results suggest that [131I]iodo-FSH first binds to FSH receptors on the plasma membrane of Sertoli cells, then FSH-receptor complexes are internalized. The increase in the number of grains over the lysosomes following longer incubation, indicates that internalized [131I]iodo-FSH or FSH-receptor complexes are subjected to degradation.
Animals↗
Properties of the binding of follicle-stimulating hormone to the fetal rat testis.
Basic properties of the binding of [131I]-labeled rat FSH ([131I]rFSH) to the testicular homogenates of fetal rats were analyzed by micro-radioreceptor assay. Specific binding of FSH was detectable in the testicular preparations from 15.5-day fetuses, but it was very low. After 17.5 days of gestation, specific FSH binding was apparent in the testis and was effectively displaced by rat FSH but not by rat LH. The Scatchard plot analyses of the binding of FSH to the testicular preparations of fetuses showed straight lines similar to those of postnatal rats, suggesting the presence of a single class of binding sites. The mean dissociation constant (Kd) for FSH receptors in 17.5-day fetuses was 0.413 +/- 0.043 nM, which was significantly greater than that in postnatal rats at 50 days of age. However, the Kd in 19.5-day fetuses was not significantly different from those in 17.5-day fetuses and postnatal rats due to its considerable variance. The capacity of FSH binding sites was 0.51 +/- 0.01 fmol/testis in 17.5-day fetuses, which was significantly less than those of 19.5-day fetuses and postnatal rats.
Animals↗
[Fundamental studies on thyroid stimulating hormone immunoradiometric assay kit (TSH RIABEAD II)].
We have reported fundamental studies on the TSH immunoradiometric assay, using TSH RIABEAD II kit (Dainabot). The sensitivity of the assay was 0.03 mu IU/ml and its C.V. was 27.2%. Intra- and inter-assay C.V. were less than 5%. Dilution test and recovery test were good. Serum TSH level was 0.3-4.0 mu IU/ml in normal subjects, less than 0.03 mu IU/ml in untreated Graves' disease and subacute thyroiditis. Therefore, it was found that the clear difference exist in serum TSH levels between normal subjects and patients with untreated Graves' disease. There was a well correlation on the serum TSH levels between this method and TSH radioimmunoassay kit (Amerlex TSH, r = 0.983). Especially, the measurement of serum TSH levels, using immunoradiometric assay kit, was useful for the diagnosis of patients with Graves' disease.
Evaluation Studies as Topic↗
Expression of simian virus 40 small t antigen in Escherichia coli and purification of the antigen.
A simian virus 40 (SV 40) DNA fragment encoding small t antigen was cloned in expression vector pUC8 for the purification of the antigen. The SV40 Hind III B fragment was inserted into the Hind III site of pUC8. A plasmid having the lacZ' and small t antigen genes in the same orientation was designated as pSVt. pSVt encodes the entire small t antigen and an extra 18 amino acids at the amino terminus of the antigen. E. coli transformed with pSVt produced hybrid small t antigen (22 kDa) which comprised about 6% of the total protein. The hybrid small t antigen reacted in immunoblot analysis with SV40-induced tumor-bearing hamster serum. Hybrid small t antigen was extracted from E. coli, and purified by preparative SDS-PAGE. The antigen was extracted from the gel using formic acid solution with high-yield. The gel-purified antigen showed the same antigenic reactivity as crude antigen.
Amino Acid Sequence↗
[Present status of hypoxic cell sensitizers and PLDR inhibitors].
Clinical and basic studies in hypoxic cell radiosensitizers and potentially lethal damage (PLD) repair inhibitors were reviewed. Most clinical trails on misonidazole (MISO) show that the toxicity of MISO is a major reason for failure in the trials and an adequate selection of tumors is needed for the success. Phase III studies on SR-2508 and RO 03-8799, less toxic and more effective sensitizers, are in progress. AK-2123 and RK-28 developed in Japan are drugs with similar clinical applicability of MISO. Thiol depletion of tumors is one of the way to increase the radiosensitization. The measurement of intercapillary distance on histopathological microslide is a valuable method to select the tumors containing much hypoxic cell fractions. Stable and effective chemicals as MISO in hypoxic cell sensitization must be developed to investigate the clinical applicability of PLD repair inhibitors.
Animals↗
Levels of topoisomerase II and DNA polymerase alpha are regulated independently in developing neuronal nuclei.
A possible correlation between activity levels of topoisomerase II and DNA polymerase alpha was studied in neuronal nuclei from developing rat brain. A high level of canonical topoisomerase II activity was detected in neuronal nuclei throughout the development even at a late stage (28 days after birth) when the activity of DNA polymerase alpha decreased to less than 2% of the fetal level. Thus, in contrast to other systems, topoisomerase II does not change in parallel with DNA polymerase alpha during neuronal development. Our results suggest that topoisomerase II is required to maintain some fundamental processes in differentiated cells, including transcription.
Age Factors↗
Radiation therapy for nasopharyngeal carcinoma. Retrospective review of 105 patients based on a survey of Kansai Cancer Therapist Group.
One hundred five patients with nasopharyngeal carcinoma were treated with radiation therapy combined with or without chemotherapy at 16 of the participating institutes in Kansai Cancer Therapist Group, Japan, from January 1978 to December 1980. The study comprised 77 males and 28 females; their ages ranged from 15 to 80 years (mean, 53 years). Five-year survival rates according to stage were as follows: Stage I, 100%; Stage II, 67%; Stage III, 44%; and Stage IV, 34%. As far as Stage IV disease was concerned, the radiation therapy only group showed significantly poorer prognosis than the combined radiation and chemotherapy group (P less than 0.05). Concerning the N stage and treatment method, the radiation therapy only group showed a higher metastatic rate than the chemotherapy combined group (35% versus 14%, P less than 0.05).
Adolescent↗
Tripolyphosphate is an alternative phosphodonor of the selective protein phosphorylation of liver microsomal membrane.
Two proteins (Mr = 145,000 and Mr = 130,000) of rat liver microsomal membrane are selectively phosphorylated in a characteristic biphasic time course by incubating the membrane with [gamma-32P]ATP in the absence of exogenously added Mg2+ (Lam, K. S., and Kasper, C. B. (1980) J. Biol. Chem. 255, 259-266). This endogenous phosphorylation system was solubilized with Triton X-100 and fractionated by chromatography with DEAE-cellulose and Sepharose 4B. The resulting preparation lacked both ATPase and inorganic pyrophosphatase activity, but retained its original character: the first phase occurred in the presence of ATP but the second phase was initiated after its depletion, implying the presence of a phosphodonor other than ATP. The putative phosphoryl donors were demonstrated to be ATP in the first phase and in the second phase tripolyphosphate, which is present in [gamma-32P]ATP preparations as a radioactive impurity. The latter conclusion was corroborated by results showing that tripolyphosphate purified from a commercial [gamma-32P]ATP and chemically synthesized [32P] tripolyphosphate were both capable of phosphorylating the two proteins and that the unlabeled tripolyphosphate competed effectively against the phosphodonor. A rapid dephosphorylation was observed in both phases upon removal of substrates during the reaction, indicating that there is a continuous turnover of the phosphoryl groups being transferred to the proteins. The second phase of phosphorylation maintained by the tripolyphosphate was shown to be reversibly inhibited by micromolar levels of ATP, ADP, and nonhydrolyzable analogues of these compounds. The implications of this unique phosphorylation system are discussed.
Adenosine Diphosphate↗
Chemosensitization by buthionine sulfoximine in vivo.
The in vivo effects of buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) biosynthesis, on the cytotoxicity of cyclophosphamide (CYM), cisplatin (CDDP) and bleomycin (BLM), were examined by monitoring the changes of non-protein thiols (NPSH) in normal tissues and in the NFSa fibrosarcoma. We used the lung colony assay as a measure of tumor response and the spleen colony assay as a measure of normal tissue response to CYM. In this study, 5 mmol/kg of BSO was subcutaneously injected four times every 12 hr before administration of the above anti-neoplastic drugs. GSH levels in subcutaneous NFSa tumors decreased to 2% of the control 12 hr after the last administration of BSO, but in the bone marrow, had recovered to 41%. In the colony assays, BSO increased the anti-cancer effects of the three chemotherapeutic agents, but did not modify the bone marrow suppression by CYM. This finding was a result of the differential response of GSH depletion in the tumor and in the bone marrow. Our study demonstrates that BSO is an effective chemosensitizer of these drugs and may be of therapeutic value when used at an optimal interval.
Animals↗