[Clinical studies of 116 cases of brain metastases of lung cancer--relative roles of surgery and radiotherapy].
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Biomedical subjects
Publications and source records attributed to M Abe.
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Pig heart lactate dehydrogenase becomes more thermostable on increasing the degree of guanidination (conversion of lysine to homoarginine) (Minotani, N., Sekiguchi, T., Bautista, J.G. and Nosoh, Y. (1979) Biochim. Biophys. Acta 581, 334-341). The conformational change of the protein on guanidination was then examined by hydrogen-deuterium (H-2H) exchange reactions. It ws found that (i) the fluctuation degrees of peptides and tyrosine and tryptophan residues in the protein decrease in that order, (ii) two H-2H exchangeable tryptophan residues per subunit are freely accessible to solvent and the fluctuation degrees of the residues does not change on guanidination, (iii) the H-2H exchange detectable tyrosine residues are not freely accessible to solvent and become less fluctuating when 15 lysine residues per subunit are guanidinated, and (iv) the peptides become much less fluctuating on increasing the degree of guanidination. The specific activity of the enzyme decreased on guanidination. The increased thermostability of the protein on guanidination may be related to the decrease in flexibility of the molecular structure by sacrificing the enzyme activity.
Two types of effect of purines on the carbachol-induced contraction of the guinea-pig trachea in the presence or absence of glucose were evaluated using dipyridamole, and adenosine uptake inhibitor. ATP exerted a greater relaxant effect on the carbachol (10(-6) M)-induced contraction than did adenosine in concentrations ranging from 10(-4) to 10(-3) M. These effects of purines were enhanced by pretreatment with dipyridamole (10(-5) M) but were virtually unaffected by the purine receptor antagonists theophylline (10(-5) M) and quinidine (10(-5) M). The contraction evoked by carbachol was gradually reduced and was almost abolished 4-5 h after exposure to the glucose-free solution. This reduction was almost eliminated by readmitting glucose, and was restored to a certain degree by introducing ATP or adenosine. ATP was less effective than adenosine. This effect of purines but not that of glucose, was markedly diminished by pretreatment with dipyridamole (3 X 10(-6) M to 10(-5) M). The restoration of the carbachol-induced contraction following introduction of purines or glucose was completely antagonized by atropine (10(-6) M). These results suggest that the extracellular effects of adenosine and ATP on the carbachol-induced contraction in normal solution are potentiated by dipyridamole, whereas the possible intracellular effects of these purines in the glucose-free solution are inhibited by this adenosine uptake inhibitor.
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The ultrasonographic appearance of hepatic hemangiomas was studied in 19 patients (31 lesions). The detectability rate by real-time ultrasonography was 77%. A hyperechoic, sharply-marginated and internally homogeneous lesion is highly suggestive of hemangioma. If the hypoechoic lesion has homogeneous internal echoes and/or strong marginal echoes, it is also suggestive of hemangioma. It is difficult to detect small lesions in the lower lateral part of the right lobe and lesions in the right lobe immediately under the diaphragm. Computed tomography should be the next procedure of choice in the evaluation process. If the computed tomography is not characteristic, angiography should be done to confirm the diagnosis.
The fine structure, histometric characteristics, and permeability of microvessels were studied by electron microscopy in normal and in ethylnitrosourea (ENU)-induced glioma tissue from rats, using horseradish peroxidase (HRP) as a tracer. The tumor vessels were classified into (1) capillary buds (Type I); (2) round small to large capillaries (Type II); (3) sinusoidal or venule-like microvessels (Type III), and (4) abnormal arteriole-like microvessels (Type IV). All endothelial cells, basement membranes and periendothelial cells in the tumor tissue demonstrated changes in structure. The most striking alterations occurred in the endothelial cells; there were abnormal endothelial tight junctions, altered pinocytotic activity, and thickening. In the tracer study, the reaction product of HRP was present around some sinusoidal or venule-like microvessels (Type III) and extended to the widened extracellular spaces around the microvessels. The endothelial cells of Type III microvessels showed decreased nuclear and mitochondrial fractions, and increased euchromatin content and a rough endoplasmic reticulum fraction. The pinocytotic vesicles with the HRP reaction product in the endothelial cells were not increased in number. Fenestrations and gaps of the endothelial cells were observed. These alterations of the endothelial cells of sinusoidal or venule-like microvessels (Type III) are considered to be the main cause of breakdown of the blood-brain barrier in this tumor.
[14C]Glutamic acid and [3H]GABA were injected into the lateral ventricle of mouse and then [14C]GABA and [3H]GABA in synaptosomes isolated from the animals were analysed. The [14C]GABA was interpreted to be newly synthesized GABA from [14C]glutamic acid while the [3H]GABA to be newly taken up GABA. We have obtained the following results: (1) when the animals were pretreated with aminooxyacetic acid and thus the GABA content in synaptosomes increased to about 2 times of the control level, only the [3H]GABA was enhanced to 3 times of the control level without any change of [14C]GABA, (2) the release of [14C]GABA from synaptosomes by high K+ depolarization was 1.5 times greater than that of [3H]GABA, (3) the releases of both [14C]GABA and [3H]GABA were increased in the presence of cold GABA, L-2,4-diaminobutyric acid or gamma-amino-beta-hydroxybutyric acid, but only slightly increased in the presence of beta-alanine. These results would suggest that newly synthesized GABA and newly taken up GABA localized individually in different pools, which might localize either in different nerve terminals or separately in the same nerve terminal.
The effect of single and different split radiation doses with varying rates and time intervals was investigated in an experimental system in vivo using second generation isotransplants of two mouse mammary carcinomas. The changes in the growth delay time (GDT) and tumor control rate (TCR) were analyzed, and explained by a dose dependence of the repair of sublethal radiation damage, reoxygenation and cellular repopulation in the tumors. A direct relationship was found between the size of the first of two dose fractions and the time interval between two exposures at which treatment with split doses is most effective in delaying or preventing tumor growth. Multiple exposures to unequal dose fractions are more effective than to equal fractions with the same total dose.
The effects of step-up (42 leads to 44 degrees C sequence) and step-down (44 leads to 42 degrees C sequence) heating were studied on the skin of C3H/He mouse feet. Skin damage in mouse feet exposed to 44 degrees C alone became proportionally more severe with increasing exposure time, while it was slight or not observed at 42 degrees C for up to 2 hr. Preheating to 42 degrees C for 60 or 120 min (step-up) had little effect on the damage from 30-60 min exposure at 44 degrees C, but increased the damage seen with 90 min at 44 degrees C. However, skin damage was markedly enhanced by exposure to step-down heating. On the other hand, thermal resistance was induced in the mouse skin by 44 degrees C fractionated treatments. The induced thermal resistance reached a maximum with a 1 day interval, and then disappeared after a 3 day interval. In another fractionation schedule of step-down heating, the enhanced skin damage which was observed when here was no interval, recovered rapidly and attained an additive response within a 1 day interval. No thermal resistance was observed.
Effects of carrageenan and gamma-irradiation on virus titre in the liver were observed after intravenous inoculation of 8 X 10(3) p.f.u. of ectromelia virus which was not lethal for untreated mice. Trapping of virus by the liver within 30 min and an initial transient reduction in titre by day 1 were not affected by gamma-irradiation but were inhibited by pretreatment with carrageenan. An increase from day 1 to day 3 was not affected by gamma-irradiation but was augmented by pretreatment with carrageenan. Therefore, protection within 3 days may depend principally upon carrageenan-sensitive and irradiation-resistant cells, namely, fixed macrophages. Elimination of virus from day 4 to day 7 depended upon cell-mediated immunity. When carrageenan was given 3 days after virus inoculation, the titre of virus increased progressively from day 4 ultimately to kill the hosts. The cytotoxic activity of spleen cells against infected target cells was raised in carrageenan-treated mice as well as in untreated mice. Immune elimination of virus may be mediated by a mechanism requiring the cooperation of sensitized T lymphocytes and blood monocytes.
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Effects of L-carnitine on ventricular arrhythmias and myocardial metabolism in a reperfused ischemic myocardium were studied in 35 anesthetized mongrel dogs. The left anterior descending coronary artery was ligated for 40 min and then reperfused for 15 min. L-carnitine (100 mg/kg) was administered intravenously 5 min before the coronary ligation and infused continuously at a rate of 20 mg/kg/min from 5 min before the reperfusion to the end of the experiment. Electrocardiograms were recorded continuously throughout the experiment. Transmural myocardial samples were obtained from both the ischemic and the nonischemic areas after 15 min of reperfusion and used for the determination of ATP, free carnitine, long chain acyl carnitine and long chain acyl CoA. L-carnitine significantly reduced the incidence rate of ventricular fibrillation after reperfusion (from 29% in the controls to 5%, p less than 0.05). ATP in the ischemic myocardium in the L-carnitine group was significantly higher than that in the control group (p less than 0.05). Free carnitine in the control group significantly decreased in the ischemic area as compared with the nonischemic area (p less than 0.01). In L-carnitine group, on the other hand, no difference was observed between them. Long chain acyl CoA in the control group significantly increased in the ischemic area as compared with the non-ischemic area (p less than 0.01). In L-carnitine group, on the other hand, no difference was observed between them. Thus, the accumulation of long chain acyl CoA in the ischemic myocardium was reduced by the L-carnitine treatment. These data suggest that L-carnitine has protective effects on ventricular arrhythmias and on metabolic changes after coronary artery reperfusion following coronary artery occlusion.
Diabetic autonomic neuropathy was expressed quantitatively using the coefficient of variation of R-R intervals (CVR-R) in ECG and its critical level where diabetics were plagued with various symptoms was investigated. The subjects were 58 diabetics under the age of 40 years. ECGs were recorded in the resting supine position and the degree of autonomic neuropathy was expressed as CVR-R by processing 100 consecutive R-R intervals. Symptoms caused by diabetic autonomic neuropathy were determined using a questionnaire. CVR-R were 1.10 +/- 0.34% (mean +/- SD) and 4.31 +/- 2.01% in patients with and without orthostatic hypotension respectively, the former being significantly lower. CVR-R were 1.30 +/- 0.88% and 3.81 +/- 1.31% in those with and without impotence respectively, the former being significantly lower. CVR-R were 0.80 +/- 0.14% and 3.85 +/- 2.17% in those with and without diabetic diarrhea respectively, the former being significantly lower. Concerning sweating abnormality CVR-R were significantly reduced in subjects exhibiting gustatory sweating (1.52 +/- 0.74%) and hypohidrosis (2.26 +/- 1.44%) when compared to those without these symptoms. From the results obtained, a CVR-R of 2% can be considered as the critical level which determines whether symptoms due to diabetic autonomic neuropathy will appear or not.
The effects of long-term treatment with gliclazide on diabetic retinopathy and platelet adhesion were investigated. The subjects comprised 25 patients with NIDDM, of which 12 cases and 13 cases were treated with gliclazide and glibenclamide respectively. An improvement in retinopathy was observed in 7 out of 12 cases in the gliclazide-treated group. Of the remaining 5 cases, four cases remained unchanged and one deteriorated. Of the 13 cases treated with glibenclamide, on the other hand, only two cases showed an improvement in retinopathy after treatment, 7 cases remained unchanged and 4 cases deteriorated. The values for the platelet adhesion test following 3 years treatment were 52 +/- 14% and 42 +/- 17% in the gliclazide and the glibenclamide-treated groups respectively. These results were not statistically significant. These data indicate that gliclazide might be more effective than glibenclamide with respect to either improving diabetic retinopathy or preventing its progression.
The diurnal blood glucose profiles of 15 unstable diabetics were continuously monitored by the artificial endocrine pancreas (AEP, Biostator). Then, feedback control (FC) with the AEP was performed on each subject for 24-32 hr. Based on the data obtained from FC, the patients received an intensified conventional insulin therapy (ICIT) consisting of two daily mixed injections, 45-60 min prior to meals. There was a negative correlation between the MAGE and the sum of serum CPR in a 50 g OGTT, before FC. The M-value, MBG and MAGE decreased significantly during FC and remained lower one month later, compared with those values obtained before FC. The ICIT caused a noticeable decrease in HbA1 levels one to four months after FC. The ICIT was characterized by an increase in the proportion of short-acting insulin in the daily insulin dosage to 40. 3 +/- 11.5%. The proportion of daily insulin dosage to body weight also increased to 0.73 +/- 0.17 U/kg. These results suggest that the AEP, Biostator, could be useful in the clinical management of unstable diabetics by providing a more precise estimate of patients insulin requirements, especially those of short-acting insulin, leading to a better long-term control of blood glucose.
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