[Follow-up of serum HGH and PRL levels in pituitary adenomas].
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Biomedical subjects
Publications and source records attributed to F Sato.
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Experimental microvascular anastomosis using a glutide copolymer (lactide:glycolide, 80:20) as an external splint was undertaken in 33 rats between the carotid artery and the jugular vein. Both vessels were dissected free over a 1-cm length and cut at the cranial end of the dissected part. The carotid artery was then introduced into a glutide pipe-splint. The arterial wall was turned 180 degrees over the edge of the splint. This reflected artery wall and the glutide were covered by the freed-up jugular vein. One stitch was made around the vein, the artery, and the glutide in a manner similar to binding steel wire over a barrel. Thus, the "one-knot anastomosis" was completed. The patency rate at the anastomosed site was 100%, confirmed by angiography in 30 rats and by direct surgery in three. The time required to produce the anastomosis was between 5 and 7 minutes. Light microscopic observation showed that there was no obstruction by thrombus formation at 1 and 5 weeks after the anastomotic surgery. This technique may be clinically applicable for extracranial-intracranial bypass surgery, reconstruction of venous sinuses, and other vascular procedures.
Characterization of OH-induced free radicals using 3'-UMP and poly(U) was performed by a method combining spin-trapping and radical chromatography. A N2O-saturated aqueous solution containing 3'-UMP and 2-methyl-2-nitrosopropane as a spin-trap was X-irradiated. The spin adducts generated by the reactions of OH radicals with 3'-UMP were separated by paired-ion HPLC and the separated spin adducts were identified by ESR spectroscopy. In the case of poly(U), the spin adducts were digested to oligonucleotides with RNase A and then separated and identified in the same manner as 3'-UMP. The free radicals observed for poly(U) were identical to those for 3'-UMP. The 5-yl radical and the 6-yl radical were identified as precursors of various oxidized products of the base moiety, and the 4'-yl radical and 5'-yl radical, formed by H-abstraction at the C-4' and C-5' positions of the sugar moieties, respectively, were identified as precursors of strand breaks. The 1'-yl radical, produced by H-abstraction at the C-1' position of the sugar moiety, was also identified. From the similarity of the free radicals of 3'-UMP and poly(U), it is suggested that the reactivities of OH radicals with nucleotides are identical to those in polynucleotides.
The effects of environmental pH on the binding and cytotoxicity of the antitumor proteins neocarzinostatin (NCS) and SMANCS [copoly(styrene-maleic acid)-conjugated NCS] to cultured cells were studied by using their fluorescent-labeled derivatives (F-drugs). At 37 degrees C the binding of these drugs to HeLa cells was pH dependent: The amount of cell-bound drugs increased with an increase in the acidity of the medium. The pH-dependent change in the binding of the drugs was not as evident at 0 degree C. The cytotoxic action of these drugs was much more rapid at acidic pH compared with that at neutral or slightly alkaline pH. Furthermore, F-drugs could be utilized to probe the microenvironmental pH in Meth-A cells, in which the drug was located by the ratio of fluorescent intensities at 450 and 490 nm. The environment of the cell-bound F-drugs became acidic with incubation time at 37 degrees C but not at 0 degree C. Inasmuch as these drugs directly attack DNA, these results suggest that NCS and SMANCS are translocated across the membrane of acidic vesicles into the cytosol after endocytotic uptake. This hypothesis is also supported by the finding that NH4Cl and chloroquine protected HeLa cells against the cytotoxicity of the drugs. Data also showed that the hydrophobic polyanion conjugate SMANCS had a much greater cell binding (10 times) and more rapid internalization compared with NCS. Taken together, our results show that acidic pH of tumor tissue is preferable for effective binding and internalization into cytosol for NCS and SMANCS.
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A case is presented of a 64-year old woman with pulseless disease associated with multiple intracranial aneurysms which were located in the internal carotid circulation at the left internal carotid-ophthalmic artery and the left internal carotid-posterior communicating junction, and in the basilar-vertebral circulation, at the left basilo-anterior inferior cerebellar artery junction and at the top of the basilar artery. Autopsy verified that her death was due to rupture of the aneurysm at the top of the basilar artery. From the cerebral angiographic and autopsy findings, it can be presumed that overloaded intracranial hemodynamic forces played some role in the development of the aneurysms. The present case is discussed together with our three previously reported cases.
The effect of increasing doses of exogenous gonadotropin stimulation for ovarian hyperstimulation was studied utilizing mouse embryos fertilized in vivo or in vitro. Increased rates of embryo degeneration, fragmentation, and triploidy, increased sister-chomatid exchange, and decreased fertilization rates were observed in high-dose stimulation groups. It appears, therefore, that oocyte and/or embryo quality may be affected by increased amounts of exogenous gonadotropin stimulation.
The influence of dissolved gases (O2, Ar, N2O, and CO2) on the chemical and biological effects of 1.2 MHz continuous wave ultrasound was investigated. Spin-trapping of OH and H radicals with 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) and observation of iodine liberation from a potassium iodide-starch solution were employed for monitoring the chemical effects, while lysing of mouse L5178Y cells was employed for monitoring the biological effects. The effectiveness of the dissolved gases in producing OH-DMPO adducts and H-DMPO adducts was O2 greater than Ar greater than N2O = CO2 approximately equal to O and Ar greater than O2 = N2O = CO2 approximately equal to O, respectively. A result similar to the yield of OH-DMPO was obtained from the liberation of iodine induced by ultrasound. In addition, the effectiveness of the dissolved gases in lysing mouse L5178Y cells by ultrasound was O2 = Ar greater than N2O = CO2 approximately equal to O. These results suggest that both dissolved N2O and CO2 gases in solution suppressed not only the chemical effect but also the biological effect.
The reactions of the hydrated electron with histone H1, protamine and related compounds (poly-L-lysine, poly-L-arginine and poly-D,L-alanine) were investigated by the spin-trapping technique. In order to identify the radical structure of the spin-adducts originating from macromolecules, the usual spin-trapping technique was developed as follows: N2-saturated aqueous solutions of proteins containing sodium formate were X-irradiated (4.5 kGy) in the presence of 2-methyl-2-nitrosopropane (MNP) as a spin-trap. The side-products due to the self trapping of MNP radicals were then removed from the spin-adducts of the proteins by a Sephadex G-25 column. Finally the spin-adducts were enzymatically digested to transform the broad e.s.r. signals due to slow tumbling of nitroxyl radicals to identifiable ones. The e.s.r. spectra obtained for all samples showed that the deaminated radical, R--CH--CO--NH--(R:amino acid side chain), was produced. Furthermore, polyacrylamide gel electrophoresis of the irradiated protamine and histone H1 indicated reduction of molecular size. These results confirm that hydrated electrons react with proteins and induce the deamination reaction which leads to main-chain scission.
Free radicals produced by X-irradiation of N2O-saturated aqueous solutions of purine nucleosides (2'-deoxyadenosine, adenosine, 2'-deoxyguanosine, 3'-deoxyadenosine, guanosine and inosine) and the corresponding homopolymers (poly A and poly I) have been investigated by the technique of spin-trapping and e.s.r. spectroscopy. 2-Methyl-2-nitrosopropane was used as a spin-trap. For 2'-deoxyadenosine and 2'-deoxyguanosine, the resulting spin-adducts were separated by Bio-Gel P-2 column chromatography and analysed by e.s.r. spectroscopy. For homopolymers, e.s.r. spectra were recorded at 50 degrees C after enzymatic digestion to obtain signals with narrower line width. The e.s.r. signal consisting of only a primary triplet without further splittings, which is consistent with assignment to the trapping of an H-abstraction radical at the C4' position of the sugar moiety, was observed in all cases. For 2'-deoxyguanosine an e.s.r. signal consisting of a secondary triplet was observed. Examinations using other spin-trapping reagents such as PBN, 4-PyOBN and DMPO provided no positive evidence supporting the proposal that this was due to an alpha-nitrogen. The e.s.r. signal consisting of a secondary doublet which further splits into a doublet was observed for 2'-deoxyadenosine, adenosine, 3'-deoxyguanosine, 2'-deoxyguanosine, and inosine, and tentatively associated with a radical centered in the sugar moiety.
Fourteen cases of inflammatory fibroid polyp of the stomach were studied in terms of immunohistochemistry and ultrastructure. They occurred as polypoid lesions in the antrum, except for two found in the body of the stomach. Out of the 14 cases, two were found to be multiple and the remainder solitary. In all but one lesion, the mucosal layer was involved and six lesions were entirely localized within the mucosal layer, suggesting that inflammatory fibroid polyps of the stomach originate in the mucosal layer. Neither S100 protein, factor VIII-related antigen, alpha 1-antitrypsin nor lysozymes were found in the cytoplasm of the proliferating cells. The ultrastructures of the proliferating cells were fibroblastic rather than neurogenic, angiogenic, or myofibroblastic. These findings suggest that the cells are fibroblasts, though the possibility that they are facultative fibroblasts remains. An interesting observation made with electron microscope was the infection of micro-organisms similar to mycoplasma. This seems to deserve further investigation as a possible etiologic factor of the disease.
In an attempt to clarify the mechanisms regulating the release of atrial natriuretic peptide (ANP) in man, ANP levels in pulmonary arterial plasma determined by RIA were correlated to hemodynamic variables in 17 patients with heart disease who underwent cardiac catheterization and angiocardiography. In addition, plasma ANP levels in various blood vessels were determined in 7 patients with heart disease and in 7 normal subjects to determine the source and the site of removal of circulating ANP. A significantly positive correlation was found between plasma ANP levels and mean pulmonary arterial wedge pressure, while the correlation between plasma ANP levels and mean right atrial pressure was not significant. After the injection of contrast medium, both mean right arterial pressure and plasma ANP levels increased, and a significant positive correlation was found between the two variables. When ANP levels in plasma collected from various blood vessels were compared, the highest levels were found in the coronary sinus. Plasma ANP levels in the renal vein were the lowest and were 50% of the levels in the aorta. Plasma ANP levels in the superior vena cava and internal jugular vein were higher than that in the antecubital vein. Analysis of immunoreactive ANP in pooled plasma by high performance liquid chromatography revealed that the retention time of the main ANP peak coincided with that of synthetic human alpha ANP. These results indicate that circulating ANP mainly originates from the heart, the kidney rapidly takes up a significant amount of ANP from the circulation, and an increase in both left and right atrial pressure triggers ANP release in man.
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SMANCS is a conjugate protein of copolymer of styrene-maleic acid [SMA] (molecular weight: 1,500) and an antitumor protein neocarzinostatin [NCS] (molecular weight: 11,700). It has an approximate molecular weight of 15,000. We report here stability of SMANCS in oil and in water, and NCS in water, under various physical conditions such as exposure to heat, UV, pH, and ultrasonic treatment. Then, we carried out an experiment of transfer of SMANCS in lipid contrast medium [lipiodol] (oil phase) to water phase (blood and physiological saline) in vitro. Results are summarized as follows: In aqueous condition, SMANCS is far more stable than NCS against the exposure to heat and UV, though it is inactivated by excessive exposures. SMANCS in an oily medium was found much more stable even at higher temperatures than in the aqueous phase. Both SMANCS and NCS are the most stable at pH 4.9-6.0. SMANCS dissolved in oil transferred to water phase slowly, having T1/10 of 24 hours (in case of lipiodol). This helps maintaining the anticancer effect of the drug in vivo for a long period of time. SMANCS in lipiodol was found to exert its action against cultured tumor cells as in an aqueous solution.
Free radicals produced by the reactions of OH radicals with uridine were investigated by a method combining ESR, spin-trapping, and liquid chromatography. A N2O-saturated aqueous solution of uridine, containing 2-methyl-2-nitrosopropane as a spin-trap, was X-irradiated and the resulting spin-adducts were separated by gel permeation chromatography and reverse-phase HPLC. ESR and uv-absorbance spectra obtained from the separated spin-adducts show that 5-yl and 6-yl radicals are produced by OH addition to the 5,6 double bond of the base moiety. It is also shown that radicals due to H abstraction from the sugar moiety at the C-4' and C-5' positions are produced.
The teratogenic effects of feeding pregnant mice with the levels of zinc that were severely deficient (0.5 ppm), marginally deficient (10 ppm), or zinc replete (50 ppm) were studied. All groups of animals were fed the experimental diet from 1-18 days of gestation (dg) except for one additional group which received 0.5 ppm Zn diet from 5-14 dg. The effects of a single dose of 2.0 mg/kg of cadmium chloride (CdCl2) injected on 8 dg in mice fed the marginally zinc-deficient or the zinc-replete diets were also investigated. We found that more than 95% of fetuses exhibited a variety of external and skeletal malformations in the severely zinc-deficient groups and that the frequency of malformed fetuses in the marginally zinc-deficient group was similar to that of the control animals. Injection of CdCl2 produced a significant increase in the incidence of malformations in the marginally zinc-deficient mice, but not in zinc-replete animals. These results demonstrate that severe zinc deficiency is teratogenic in mice and that a marginal zinc intake influences the teratogenic potential of cadmium.
Two cases, one of a chronic encapsulated intracerebral hematoma occurring in a 43-year-old man and the other of an intracerebellar hematoma in an 8-year-old boy, are reported. In both cases CT scans revealed an encapsulated lesion containing the hematoma, but angiographic pictures were poor except for revealing a space-occupying lesion and a small vascular lesion. Both hematomas were successfully removed. Each case was associated with a thick, fibrous capsule that was found histologically to arise from an occult angiomatous malformation. The encapsulated hematomas partially included old thromboses, and both old and recent areas of hemorrhage. The latter were considered to be due to the rupture of vessels developed near the inner surface of the thickest part of the fibrous capsule. Although the condition is uncommon, chronic hematoma must be considered when encapsulated mass lesion is present in the brain.