[Fixation device for pneumoencephalography with lumbar puncture and its clinical application].
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Biomedical subjects
Publications and source records attributed to R Horie.
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1. L-Dopa induced a 56% increase in frontal cortical blood flow (fcCBF) one hour after intraperitoneal administration in stroke-prone spontaneously hypertensive rats. The treatment with carbidopa did not alter the magnitude of the response but shortened the response time to half an hour. In stroke-resistant rats and in Wistar Kyoto rats, L-dopa decreased fcCBF. This response was reversed to different degree by carbidopa pretreatment. 2. Serotonin decreased fcCBF in all groups. L-Dopa administered one hour after serotonin resulted in a recovery to the control level in SHR-SR, an increase in fcCBF in WK but the decreased flow in SHR-SP was maintained till the end of the observation time. 3. The data suggest that the stroke-prone rats have an unusual response to L-dopa and that L-dopa and this combination with a peripheral decarboxylase inhibitor may have a beneficial effect on the improvement of cerebral blood flow especially when the pre-existing level of cerebral blood flow is reduced in severe hypertension.
The feeding of a normal diet containing 13.5% urea (in place of protein in a high protein diet) attenuated the development of severe hypertension and decreased the incidence of stroke in spontaneously hypertensive rats (SHR), when 1% NaCl solution was given to them. The urea not only increased urine volume, but also increased urinary sodium excretion in SHR given 1% NaCl for drinking. Although there was no obvious difference in erythrocyte size between the urea and the control groups, there was a significant inverse correlation between plasma urea level and erythrocyte size. These results suggest that a high protein diet reduced blood pressure partly through the diuretic effect of urea, the common metabolite of various proteins.
Stroke-prone spontaneously hypertensive rats (SHRSP) and stroke-resistant SHR (SHRSR) exhibited an increased preference for a 2% NaCl solution, relative to water, in comparison with normotensive Wistar-Kyoto (WKY), but the preference was lost quickly in SHRSP with unbroken exposure. Neither a high protein diet (50% fish protein) nor a low protein diet (5% protein) changed the salt water preference in SHRSR and the former abolished the preference more quickly in SHRSP. The fish protein diet, however, increased the ratio of urinary sodium excretion to dietary sodium intake in the first three days of exposure to a high salt intake in all groups. Results from this experiment suggest that an increased dietary protein intake can facilitate sodium excretion and may possibly ameliorate the adverse effect of a high sodium diet.
In a previous study, we obtained a novel monoclonal antibody (F1 alpha-75) directed against a synthetic mucin antigen termed F1 alpha, and demonstrated that this antigen was expressed in a high percentage (80.2%; 89/111) of gastric carcinomas. In the present study, we compared the expression of F1 alpha with that of sialyl-Tn antigen, a mucin antigen similar to F1 alpha, in 54 human early gastric carcinomas, intestinal metaplasia and adenomatous polyps of the stomach to determine how differences in the expression of these antigens correlated with gastric carcinogenesis. The rate of expression of F1 alpha in early gastric carcinoma tissues, 81.5%, was higher than that of sialyl-Tn antigen, 57.4%. No correlation was found between the rate of expression and histological type, depth of cancerous invasion or lymph node metastasis. Sialyl-Tn antigen was extensively expressed in 77.5% of specimens of complete intestinal metaplasia and in 78.6% of those of incomplete intestinal metaplasia; however, the expression of F1 alpha in those specimens was rare and sporadic, with rates of only 25.0 and 27.7%, respectively. In adenomatous polyps, the rate of expression of F1 alpha is 6.25% and that of sialyl-Tn antigen is 43.8%. Our findings indicate that F1 alpha is a more specific antigen for gastric cancer than sialyl-Tn antigen, and that F1 alpha is an antigen associated with carcinogenesis of the stomach.
The incidence of cerebral lesions in stroke-prone spontaneously hypertensive rats appears to depend on the severity of the hypertension and nutritional factors. Comparison of American and Japanese commercial rat diets revealed a much higher incidence of stroke in rats receiving the Japanese diet (88% vs 30% by 9 months of age). Analyses of the diets indicate that perhaps the most important difference in the two diets is the protein content. Based on complete amino acid analyses of the protein in these diets, it appears that the American diet contains about 22% protein as compared to about 15% for the Japanese diet. Minor differences in vitamin and mineral contents are not remarkable. Comparison of the findings in this experimental rat model with epidemiologic studies suggest that nutritional factors may also play a role in the incidence of stroke in humans.
Platelet aggregation induced by 5 microM adenosine 5'-diphosphate (ADP) was significantly higher in men with a family history of essential hypertension than in men without such a history when they were fed a low fat-cholesterol diet with low salt. Platelet aggregation activity was remarkably increased in both groups when the diet was changed from low salt into high salt. Platelet aggregation activity was higher in the group with a positive family history of hypertension on the low fat-cholesterol plus high salt diet than in the group without a family history under the same conditions. The activity was slightly increased in both groups when fed a high fat-cholesterol diet with low salt. There was no significant difference in the platelet aggregation between the two groups. The activity was significantly increased in both groups on the high fat-cholesterol diet after the diet was changed from low salt to high salt. Under both the low and high fat-cholesterol diets, the mean blood pressure was significantly elevated in response to excessive salt intake in the group with a family history of essential hypertension, but it was not elevated in the group without such a family history.
Interrelationships among blood pressure (BP), sodium (Na), potassium (K), dietary protein, and serum cholesterol level (Chol) were examined in 62% (1120) of 1818 Japanese inhabitants of both sexes aged over 30 years who lived in a rural village in Japan. Fasting single-spot urine specimens were collected in the morning to measure Na, K, urea nitrogen (UN), inorganic sulfate (SO4), and creatinine (Cr). The Cr ratios of Na, K, UN, SO4, Na/K, and SO4/UN were analyzed by multiple regression analysis to determine independent associations with BP together with age, obesity index, hematocrit (Hct), Chol, triglyceride (TG), and fasting serum glucose level (Glu). Except for Na/Cr in men, Na/Cr and Na/K were found to be independently and positively related to BP, particularly to systolic BP (SBP). In contrast, K/Cr and SO4/UN (an index related to the dietary score of sulphur-containing amino acids derived mainly from animal protein) were both negatively associated with SBP, and UN/Cr (an index of total protein intake) was positively associated with SBP in men. Chol was linked to BP negatively in men but positively in women. Age, obesity index, TG, and Hct were generally positively and significantly related to BP in both sexes. The results confirmed on epidemiological grounds the positive link of Na and the negative link of K to BP within a single population in Japan. They further suggest, although only in men, that there is a negative relationship of Chol and dietary animal protein with BP.
Since the early development of structural cardiovascular change in spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) indicated the involvement of non-pressure-dependent factors in this process in hypertension, smooth muscle cells (SMC) from the aorta of SHR, SHRSP, and normotensive Wistar-Kyoto rats (WKY) were investigated under tissue culture conditions free from blood pressure and humoral factors in vivo. By the observation of such factors as growth rate and DNA or protein synthesis vascular SMC from these rats with genetic hypertension were proved to have intrinsically greater growth activity independently of blood pressure. Although serum from SHR and SHRSP had no specific stimulative effect on SMC growth, circulating epinephrine may accelerate cardiovascular structural changes because isoproterenol added to the culture media enhanced ornithine decarboxylase (ODC) activity. Moreover, SMC from SHR and SHRSP showed greater thymidine incorporation than those from WKY even in response to lower extracellular Na+ concentration. Local nutritional conditions of SMC, which were proved to have a great effect on the morphology and structure of cultured SMC, may be a basic determinant of the development of hypertension-induced structural vascular changes or lesions.
Dopamine and norepinephrine fluorescence in the nucleus caudatus and putamen and cerebral cortex was markedly depleted along with rCBF reduction in symptomatic stroke-prone spontaneously hypertensive rats (SHRSP) with bilateral carotid artery ligation under light pentobarbital anesthesia. An accumulation of fluorescence at the intima of blood vessels, especially in the nucleus caudatus and putamen, was noted in some SHRSP under the same experimental conditions. These changes were hardly seen in deeply anesthetized SHRSP, as well as in normotensive Wistar-Kyoto (WK) rats. It may be possible, therefore, that released cerebral amines in acute brain ischemia accelerate the vasoconstriction and permeability of cerebral arteries, which further decreases the blood supply to these areas. Also, a barbiturate protective effect against the release of central dopamine and norepinephrine during acute brain ischemia was noted in deeply anesthetized SHRSP.
Glucose metabolites in the rat brain were measured under various stages of ischemia. In acute ischemia induced by bilateral carotid artery ligation, phosphocreatine and ATP levels were significantly decreased and lactate levels were significantly increased in stroke-prone spontaneously hypertensive rats (SHRSP). These extreme changes were not observed in normotensive Wistar-Kyoto rats (WKY) and stroke-resistant spontaneously hypertensive rats (SHRSR), under the same conditions. In chronic ischemia induced by long-lasting regional cerebral blood flow reduction due to severe hypertension, similar changes were observed only in SHRSP at the advanced stage. The levels of glucose metabolites in the brain were confirmed to be well maintained within control ranges even though the cerebral tissues were subjected to the chronic ischemia related to severe hypertension.
The predilection sites of cerebrovascular lesions (cerebral hemorrhage and/or softening) were studied in 1,278 stroke-prone spontaneously hypertensive rats (SHRSP). The precise supply to the main cerebral arteries was determined by trypan blue injections and microangiography. The three major territories were the anteromedial cortex, the occipital cortex, and the basal ganglia. A common angioarchitectural characteristic of these three areas was the blood supply through "recurrent branching" from the main stream. In the basal ganglia, where there is a preponderance of lesions, the arteries responsible for these lesions belonged to the lateral group of lenticulostriate arteries. The primary pre-stroke arterial lesions were further studied microangiographically in SHRSP killed at the time the initial symptoms of stroke were detected. These points were located at the "boundary zone" of the main cerebral arteries. Our findings indicated the importance of these two angioarchitectural minor loci as the basis for functional or organic circulatory disturbances that may cause stroke. Since these local factors of stroke are common in the cortex and basal ganglia of rats and basal ganglia of humans, these SHRSP are regarded as good pathogenetic models for studies on stroke in humans.
A new model for studies on atherogenesis in the cerebrovascular system was obtained by using recently established stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP on a hypercholesterolemic diet (20% suet, 5% cholesterol, and 2% cholic acid) had ring-like fat deposits in the circle of Willis, which were detected within a few weeks by new techniques for the macroscopical demonstration of fat deposits "as a whole" and were proved to be good quantitative indices for the initiation of atherogenesis. Experimental studies using more than 200 rats including SHRSP, experimental hypertensive rats (renal infarction hypertension) and WK rats, fed a hypercholesterolemic diet with 1% salt in the drinking water for 1 week, 2 weeks, 10 weeks and more than 10 weeks, revealed that the arterial fat deposition in the brain was affected by BP, serum cholesterol level, strain difference and age. High BP was confirmed to be more important than the other factors by the quantitative analysis of sudanophilic rings in relation to BP.
Cerebrovascular ring-like fat deposition, which was noted only in hypertensive rats but never observed in normotensive rats even after they had been fed a high-fat cholesterol (HFC) diet for a long time, was successfully developed in the posterior communicating or other cerebrobasal arteries in normotensive rats fed an HFC diet for ten weeks after bilateral or unilateral carotid artery ligation or basilar artery ligation. These posterior communicating arteries with fat deposits were clearly dilated to a significant extent. These findings corroborated the fact that not only high blood pressure but also hemodynamic derangements induced by hypertension or other causes were important factors for the development of fat deposition in cerebral arteries.
Regional cerebral blood flow (rCBF) was repeatedly measured by the hydrogen clearance method in the frontal cortex of stroke-prone spontaneously hypertensive rats (SHRSP) at the age of 50 days and thereafter. When SHRSP rats developed severe hypertension (over 200 mg Hg at the age of 60 days) rCBF began to decrease abruptly in the frontal cortex--one of the three predilection sites of stroke in these rats. In contrast, such a reduction in rCBF was not noted in either stroke-resistant spontaneously hypertensive rats (SHRSR) which developed moderate hypertension (under 200 mg Hg), or in Wistar-Kyoto rats (WK) with normal blood pressure (under 15 mm Hg). A similar marked reduction of rCBF with severe hypertension (over 200 mm Hg) was also detected in apoplectic gene-free renal infarction hypertensive rats (RHR) experimentally produced from age-matched WK animals. Blood samples were obtained through an implanted femoral artery canula without disturbing the nonanesthetized SHRSP, SHRSR and WK rats. Arterial blood gas analysis (PaCO2, PaO2 and pH) showed no significant differences at the age of 5 months in any of these rats. Chemical cerbrovascular reactivity, that is, an increase in rCBF in response to CO2 inhalation, showed no significant difference among SHRSP rats from the age of 50 days to 5 months. However, it markedly decreased in SHRSP rats at the age of 9 months and thereafter (the average age of male SHRSP rats which develop stroke is 9 months). The present study showed stroke did not occur in antihypertensive agent-treated SHRSP rats. In these SHRSP rats rCBF did not decrease as long as blood pressure was well-controlled.