[Central diabetes insipidus caused by neurosarcoidosis].
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Biomedical subjects
Publications and source records attributed to Y Meguro.
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We examined the effect of age on working memory with a reading span task (RST) together with other verbal span tasks. Sixty-two participants were divided into three subgroups (young, middle-aged, and elderly). The RST performances were significantly different among all the subgroups. To elucidate which component of the working memory system is affected by age, we performed an analysis of covariance with the scores of simple and complex verbal span tasks as covariates. From the results, we conclude that the difference of the RST performance between the middle-aged and elderly groups reflects a decline in the capacity of the phonological loop, and the difference between the young and middle-aged groups reflects malfunctioning of the central executive system.
In an early-life, a memory disturbance affects the learning and school record directly. Furthermore, it may cause the problem of maltreatment or adaptation difficulty for school life. We report a child amnesia caused by a traumatic brain injury when she was 9 years old. We examined her episodic and semantic memory. We developed 3-steps tasks of recognition and recall for the post-accident episodic memory. First, the examiner presented the patient with four words orally including a label of her episode, and asked her to choose one that she felt familiar with (the recognition of the episodic label). Second, if the word she selected was correct, she was required to recall the episode related to the word (the recall of the episode). Third, if she could not recall the episode herself correctly, she was required to choose a correct sentence about the episode (the recognition of the episode). She could not recall episodes correctly, but produced confabulation instead. She showed, however, good recognition of each episode. Furthermore, we performed recognition tests of time, person, and place about the same post-accident episodes, which were poor especially for time. In semantic memory tasks, we examined about kanji characters (ideogram) learned from the first grade to the sixth grade and mathematical knowledge learned from the second grade to the sixth grade at elementary school ("What centimeters is equal to one meter?" or "Tell me the formula of the size of a circle." etc). We found that she showed a retrograde impairment for about one year. For both episodic and semantic memory, she showed an anterograde impairment. Because of the anterograde amnesia she could not acquire new facts, and also showed para-amnesia or confabulation. In a child with brain damage, neuropsychological assessment is important in predicting effect of rehabilitation and recovery of school performance.
Triethylenetetramine dihydrochloride (TETA) is a therapeutic drug for Wilson's disease. We developed a simple fluorometric method for detection of TETA in biological fluids by using high-performance liquid chromatography (HPLC), and examined TETA concentrations in the serum and urine of two healthy adults who were given TETA orally. No TETA peak was detected in the serum. The amount of TETA in the urine of the two adults was only 1.6 and 1.7% of the dose administered. However, a large unidentified peak appeared in the urine after oral administration. This peak was not observed in a mixture of TETA and control urine or in urine before TETA administration. When the urine after TETA administration was analyzed after hydrolysis with HCl, the unidentified peak disappeared, while the TETA peak increased. These findings indicate that the substance which yielded the unidentified peak is a metabolite of TETA, suggesting that most of the TETA administered is metabolized and then excreted in the urine.
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A 28-year old male was admitted to our hospital because of heart failure, chronic renal failure and nephrotic syndrome. Light microscopic findings of his kidney biopsy showed proliferation of mesangial cell and marked narrowing the lumina of small arteries and arterioles. The changes of these small vessels were not those of typical vasculitis, when we considered his age and his past history. The diagnosis of dilated cardiomyopathy was made by the findings in echocardiography and cardiac catheterization. Since the heart failure and renal disease seemed to be simultaneous initiated, it was supposed that the diseases in two organs were caused by a common pathogenesis related to that of vasculitis. When steroid pulse therapy was adopted, both of cardiac and renal function responded to this treatment (ejection fraction from 26% to 52%, creatinine clearance from 48 to 62 ml/min). Increase of CD56 positive cells (natural killer cells) in peripheral blood was ameliorated after the treatment. These findings suggest that cellular immunity may be concerned with the pathogenesis of the combination of dilated cardiomyopathy and renal disease in this case.
The copper concentration was investigated in the cultured astrocytes from macular mice, an animal model of Menkes disease. An excessive amount of copper was accumulated in the astrocytes as copper-metallothionein. These results show that the underlying genetic defect of the macular mouse is expressed in the astrocytes. A similar situation may exist in Menkes disease and cause a failure of copper transport to neurones.
The macular mouse is an animal model of Menkes disease. The neurological degeneration is caused by decreased cuproenzymes activity, such as cytochrome c oxidase (CCO), associated with copper deficiency in the brain. We investigated the age-related changes in copper concentration and CCO activity in the brain of macular mice which were given a single injection of cupric on postnatal day 7. The copper concentration in the brain of macular mice was always about 40% of that of the age-matched controls. However, the copper concentration of both macular and control mice increased with age gradually. The CCO activity in the brain of macular mice was significantly lower than that of controls at the age of 8 days. However the activity in macular mice increased with growth and reached a level equal to the controls at 180 days. These results suggest that the improvement of CCO activity in the brain of macular mice is due to the brain copper concentration which increased with age. Therefore, parenteral administration of copper is recommended especially during infancy in patients with Menkes disease.
Tritiated yohimbine binding was used to estimate platelet membrane alpha 2-adrenoceptor characteristics in normal subjects (n = 12) and patients with essential hypertension (n = 30), primary hyperaldosteronism (n = 10) and phaeochromocytoma (n = 10). There was a 20-fold increase in mean levels of resting norepinephrine and epinephrine in the phaeochromocytoma group. Total binding sites (Bmax) and dissociation constant (Kd) for 3H-yohimbine did not differ significantly among the four groups. Following curative surgery for phaeochromocytoma, plasma catecholamine levels were normalized but the Bmax remained unchanged. Following surgery for primary hyperaldosteronism, levels of plasma norepinephrine rose but Bmax was not changed. In all but the phaeochromocytoma patients, Bmax values correlated positively (r = 0.437, n = 48, P less than 0.01) with resting plasma norepinephrine. A significant negative correlation was observed between the change in plasma norepinephrine in response to postural change and resting Bmax. Treatment for 2-4 weeks with guanabenz or bethanidine induced a parallel fall in both Bmax and plasma norepinephrine. Treatment with reserpine was followed by a comparable fall in plasma norepinephrine, but Bmax values were unchanged. The findings support the view that platelet alpha 2-adrenoceptor density is functionally regulated in parallel with sympathetic nerve activity rather than circulating catecholamine levels, although it is not known which neuronal substance(s) may participate in this regulation.
1. The baroreflex-mediated changes in plasma norepinephrine (NE) and heart period (RR interval) to phenylephrine (PE)-evoked pressor and nitroprusside (NP)-evoked depressor stimulations were studied in 19 patients with chronic essential hypertension, 12 with borderline hypertension and in 11 age-matched normal controls. 2. Intravenous infusion of PE at a rate of 0.25-1.0 microgram/kg/min induced dose-related increases in mean arterial pressure (MAP) and in RR interval and a decrease in plasma NE. Similarly, NP infusion at a rate of 0.1-0.4 microgram/kg/min evoked the opposite changes in each variable. The reflex sensitivity was defined as the slope of linear regression between the changes in RR interval and MAP (RR/MAP) and between those in plasma NE (% of the baselines) and MAP (%NE/MAP). 3. Both RR/MAP and %NE/MAP for pressor and depressor stimulations were reduced below values found in normal subjects, in both chronic and borderline hypertensives. 4. The values of %NE/MAP was negatively related to the basal plasma NE during falls in blood pressure (r = -0.401, P less than 0.05). 5. The %NE/MAP may be a useful index of the sympathetic component of baroreflex sensitivity. A decrease in %NE/MAP in hypertensive and borderline hypertensive patients suggests a blunted sensitivity of the sympathetic constrictor reflexes.
The concentration of plasma free dopamine (PDA) is said to be much lower than that of other catecholamines and its physiological significance remains unclear. Our recent studies using a newly developed radioenzymatic method disclosed the fairly distinctive features of PDA in patients with various types of hypertension. PDA was also confirmed as a variable responsive to postural change, dietary sodium loading and dopamine receptor antagonist. The results suggest that PDA could be a sensitive marker to represent the peripheral dopaminergic function, which might play an inherent role as a physiological regulator responsible for the cardiovascular and endocrine system.
Functional relationships between platelet alpha 2-adrenoceptors and sympathetic nerve activity were studied in patients with essential hypertension (n = 23), primary aldosteronism (n = 10), and normal subjects (n = 12). The maximum number of binding sites (Bmax) and the dissociation constant (Kd) of 3H-yohimbine on platelet membranes and resting plasma norepinephrine (NE) were similar among these groups of subjects. In all subjects combined, Bmax values were correlated positively (r = 0.471, p less than 0.01) to resting plasma NE and negatively (r = -0.531, p less than 0.01) to the changes in plasma NE when subjects were moved from lying to standing. A 2-4 week treatment with guanabenz or bethanidine induced a parallel fall of both Bmax and plasma NE, whereas administration of reserpine caused a similar fall of plasma NE but Bmax remained unchanged. Kd values were not changed after any of these treatments. The results support the view that platelet alpha 2-adrenoceptor density is functionally regulated in parallel with sympathetic nerve activity rather than plasma NE per se. This hypothesis seems quite reasonable when it is extended to the presynaptic alpha 2-adrenoceptors; otherwise, the negative feedback function on NE release should be lessened and contradictory to its physiological role.
To investigate the effects of dietary sodium on the peripheral dopaminergic mechanism, changes of unconjugated plasma dopamine(DA) and its related humoral factors were studied in 8 patients with essential hypertension(EH) and 8 age-matched normal controls(N) while they were receiving ordinary meals (Na, 130-180 mEq daily) followed by higher sodium (250-300 mEq daily) diets for a week. Plasma and urinary DA, norepinephrine(NE) and epinephrine(E) were measured by the highly sensitive COMT-mediated radioenzymatic procedure, which permits an accurate estimation of plasma DA as low as 5-6 pg/ml. Under high sodium diets, blood pressure and heart rate were not changed significantly in N and EH subjects. Urinary NE and E tended to decrease, while urinary DA increased significantly in both groups of subjects (p less than 0.05). There was a significant correlation between urinary sodium and DA (r = 0.590, p less than 0.001), but plasma DA failed to correlate significantly to urinary sodium or DA in all subjects. Plasma NE and E tended to decrease in both N and EH subjects, while plasma DA increased significantly (p less than 0.05) in EH from 7.2 +/- 0.8 pg/ml [mean +/- SEM] to 9.3 +/- 1.0 and slightly in N from 9.1 +/- 1.8 to 11.2 +/- 1.3. Plasma renin activity(PRA) and plasma aldosterone(PAC) were invariably decreased in all subjects, while plasma prolactin(PRL) remained unchanged. A significant correlation was observed between plasma DA and NE under ordinary meals (r = 0.733, p less than 0.01), but this correlation disappeared under high sodium diets. Plasma DA showed an inverse correlation to PAC (r = 0.351, p less than 0.05) under both dietary conditions. Upright posture induced a significant rise (p less than 0.05) in NE, E, DA, PRA and PAC with ordinary meals, but the responses of NE and PAC were apparently attenuated with high sodium diets. An intravenous injection of metoclopramide (MCP, 10 mg), a DA receptor antagonist, provoked a slight rise in plasma NE and DA with ordinary meals, of which responses were further enhanced with high sodium diets. MCP induced a definite rise in PAC and PRL in all subjects under both dietary conditions (p less than 0.01), while plasma E and PRA remained unchanged after MCP challenge. The results lend support to the view that unconjugated plasma DA could be a useful marker of peripheral dopaminergic activity, which might be a physiological regulator responsible for the suppression of aldosterone secretion and sympathetic nerve activity observed during high sodium intake.
The purpose of this study is to evaluate the plasma Na, K-ATPase inhibitor (NKI) in patients with essential hypertension and to compare the mode of its biochemical actions on the Na, K-ATPase with that of ouabain. Plasma NKI was extracted through a reversed-phase cartridge column and its inhibitory action on hog brain Na, K-ATPase was measured in vitro. Plasma NKI activity was significantly greater in patients with essential hypertension (44 +/- 2.8% (S.E.), n = 28, p less than 0.01) than in normotensive controls (25 +/- 2.4%, n = 21). No significant correlation was demonstrated between the values of plasma NKI and mean arterial pressure in either group. Both plasma NKI and ouabain showed a dose-dependent inhibition on the Na, K-ATPase reaction. An action of ouabain was competitively antagonized by increased concentration of potassium in the reaction mixture, while plasma NKI showed a constant inhibition on the Na, K-ATPase independently of potassium concentrations. The action of plasma NKI was of rapid onset and linear with time, while ouabain showed a delayed onset of the reaction over 30 sec, followed by a progressively increasing inhibition on the enzyme reaction. Finally, the inhibitory action of plasma NKI on Na, K-ATPase was completely abolished in the presence of bovine serum albumin even at the concentration of 500 micrograms/ml in the reaction mixture, which did not have any influence on the actions of ouabain. To sum up, the results showed a markedly different nature of plasma NKI from ouabain in the mode of biochemical actions on the Na, K-ATPase in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Bacteria isolated from the skin of the pufferfish Fugu poecilonotus were screened for tetrodotoxin production. Tetrodotoxin and its derivatives were detected by HPLC analyses in broth cultures of a Pseudomonas sp. Upon alkali treatment the compounds yielded, as do tetrodotoxin and its derivatives, 2-amino-6-hydroxymethyl-8-hydroxyquinazoline, the identity of which was confirmed, after methylation or trimethylsilylation, by HPLC, mass spectrometry and gas chromatography - mass spectrometry.
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