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Biomedical subjects

S Higa

Publications and source records attributed to S Higa.

At least 55 records · Page 3Linked to original sources

Alpha 2-adrenergic receptor in familial amyloidotic polyneuropathy.

alpha 2-Adrenergic receptor binding has been studied in platelet membranes from 16 patients with type 1 familial amyloidotic polyneuropathy (FAP) at various clinical stages and 15 normal subjects. Binding of the radioligand [3H]yohimbine to platelet membranes was used to examine alpha 2-adrenergic receptors. The number of alpha 2-adrenergic receptors were significantly lower in patients of the early stage than in normal subjects. Then, the numbers tended to be higher than those of normal subjects in the intermediate stage, and they were higher in the single advanced-stage patient studied. The reduction in alpha 2-adrenergic receptor numbers in platelet membranes from patients of the early stage might be explained by the down-regulation of the receptors in vascular smooth muscle, but it remains uncertain whether a high number of alpha 2-adrenergic receptors observed in the single advanced-stage patient might be explained by the up-regulation of the receptors.

Adult↗

A case of von Recklinghausen's disease associated with pheochromocytoma and papillary carcinoma of the thyroid gland.

A 58-year-old woman was admitted to our hospital complaining of headache, dizziness and intermittent elevation of blood pressure. Multiple café-au-lait spots and neurofibromas had appeared on the back and the limbs since the age of 30 years. At the age of 54 years she underwent total thyroidectomy because of papillary carcinoma of the thyroid gland. On admission, the levels of plasma norepinephrine and epinephrine, urinary norepinephrine and normetanephrine were all within the normal range. However, urinary excretion of metanephrine was markedly increased to 1.49 +/- 0.45 (Mean +/- SD) mg/day and that of epinephrine was also slightly increased. The computed tomographic scans of the abdomen and the scintigraphy with 131I-metaiodobenzylguanidine revealed a tumor mass in the region of the right adrenal gland. The tumor was histologically confirmed to be pheochromocytoma at the operation. In her family history, her mother and one of her two sisters had von Recklinghausen's disease and another sister suffered from follicular carcinoma of the thyroid gland. As far as we know, this paper is the first report of a patient with von Recklinghausen's disease associated with both pheochromocytoma and non-medullary carcinoma of the thyroid gland, and her family.

Carcinoma, Papillary↗

Isolation of 2-hydroxycarboxylic acids with a boronate affinity gel.

Boric acid has been known to make a complex with 2-hydroxycarboxylic acids. Based on this principle, we have developed a new method for isolation of vanillylmandelic acid, p-hydroxymandelic acid, vanillyllactic acid, and p-hydroxyphenyllactic acid in urine. The technique involves two steps: extraction of lipophilic compounds from urine with n-butanol and selective isolation of 2-hydroxy acids in the n-butanol phase on a phenylboronate gel column. 2-Hydroxy acids were eluted from the column with 1.5 ml of 2% acetyl chloride in methanol with the recoveries of ca. 70%. According to analysis of urinary extract by gas chromatography--mass spectrometry, the mean excretion rates of the above four compounds in 12 healthy subjects were 3.68, 1.93, 0.091, and 1.08 mg/day, respectively.

Boronic Acids↗

Identification and quantification of 5-methoxyindole-3-acetic acid in human urine.

A putative pineal metabolite, 5-methoxyindole-3-acetic acid, was quantified in human urine by a gas chromatographic-mass spectrometric method. Excretion of 4.77 +/- 2.25 microgram/day (mean +/- SD) was consistent from each of three normal subjects over 2-4 weeks. Excretion did not vary with regard to menstrual cycle. The daily pattern of excretion bore no relationship to that of 6-hydroxymelatonin, the major metabolite of melatonin, indicating that the major portion of urinary 5-methoxyindole-3-acetic acid does not derive from melatonin.

Adolescent↗

Treatment of orthostatic hypotension in Shy-Drager syndrome with DL-threo-3,4-dihydroxyphenylserine: a case report.

Orthostatic hypotension in a patient with Shy-Drager syndrome was treated for 6 months with oral DL-threo-3,4-dihydroxyphenylserine (DL-threo-DOPS). Adrenergic function was evaluated before and during treatment by measurements of changes in blood pressure and plasma norepinephrine on head-up tilting and by the response of blood pressure to the Valsalva maneuver and infused norepinephrine. After the patient received DL-threo-DOPS, the fall in his mean arterial blood pressure on head-up tilting was reduced and he had no syncope when standing. When peripheral decarboxylase inhibitor was combined with DL-threo-DOPS, the same beneficial effect on orthostatic hypotension was observed.

Autonomic Nervous System Diseases↗

Decreased 6-hydroxymelatonin excretion in Korsakoff's psychosis.

Mean (+/- SEM) urinary excretion rate of the major melatonin metabolite 6-hydroxymelatonin (micrograms/day) was lower in 7 (2.8 +/- 1.0) of 8 men with Korsakoff's psychosis (KP) than in 15 healthy men (11.4 +/- 1.4). Treatment with the alpha 2-noradrenergic agonist clonidine decreased daily 6-hydroxymelatonin excretion (p less than 0.02). Reduced daily excretion of 6-hydroxymelatonin in KP reflects decreased melatonin synthesis in the pineal gland, perhaps as a residual effect of lesions due to past thiamine deficiency (Wernicke's encephalopathy).

Aged↗

Lesions of the paraventricular nucleus area of the hypothalamus disrupt the suprachiasmatic leads to spinal cord circuit in the melatonin rhythm generating system.

The circadian rhythm in melatonin production in mammals is regulated by a suprachiasmatic (SCN) leads to spinal cord leads to pineal circuit. In the present investigation the possible participation of the paraventricular nucleus of the hypothalamus (PVN) in the SCN leads to spinal cord segment of this circuit was investigated in the rat. Bilateral lesions of the PVN area were produced and one to two weeks later melatonin production was evaluated by measuring the activities of the two pineal enzymes required for the formation of melatonin from serotonin, indoleamine N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), and urinary 6-hydroxymelatonin, the major melatonin metabolite. In some cases pineal melatonin was also measured. Control animals received sham-PVN lesions. Histological examination of the lesions indicated that the PVN were bilaterally destroyed 100% in 12 animals. The nighttime pineal melatonin and urinary 6-hydroxymelatonin values in this group were reduced about 90%, nighttime pineal NAT activity was reduced about 98%, and HIOMT activity about 75%. The urinary 6-hydroxymelatonin values of PVN-lesioned animals and animals with denervated pineal glands were similar. In animals with hypothalamic lesions involving less than 30% of the PVN, nighttime values of NAT, HIOMT, and urinary 6-hydroxymelatonin were normal; in animals with 30 to 95% PVN damage these parameters were altered to a small degree. These studies, together with histochemical observations, indicate the SCN neurons responsible for pineal circadian rhythms project to the PVN area of the hypothalamus.

Acetylserotonin O-Methyltransferase↗

IgG heavy-chain (Gm) allotypes and HLA-antigens in insulin-dependent diabetes mellitus in Korea.

Eighty-eight patients with insulin-dependent diabetes mellitus (IDDM) and seventy-two unrelated normal controls in Korea were studied for Gm allotypes and HLA-antigens. Ten Gm phenotypes were found among the Korean population. The phenotype frequencies of Gm axg (1,2,21), Gm ag (1,21), Gm agb0b3b5st (1,21, 11,13,10,15,16) and Gm agfb0b1b3b4b5 (1,21,3,11,5,13,14,10) were higher than the other Gm allotypes, but there was no significant difference between patients and controls. HLA-BW54 was found in 15% of patients who had any of those Gm allotypes (Gm axg, Gm agb0b3b5st, Gm ab0b3b5st). However there was no significant difference in frequency as compared with controls.

Diabetes Mellitus, Type 1↗

Genetic studies of familial amyloid polyneuropathy in the Arao district of Japan: I. The genealogical survey.

A genealogical survey of familial amyloid polyneuropathy in the Arao district of Japan was undertaken, and the data were analysed statistically. The survey revealed 92 patients (46 males and 46 females) in 9 families. Thirty-one of the patients (16 males and 15 females) are alive. For 44 patients, the mean age of onset was 34.1 years (range 20-46 years). The penetrance corrected for late onset was 83.5% by Morton's method. The segregation ratio of 18 sibships in which one of the parents was affected was 36 +/- 6% for single ascertainment and 46 +/- 5% for complete ascertainment; the corresponding figures of 14 sibships in which neither parent was affected was 30 +/- 7% for single ascertainment and 40 +/- 6% for complete ascertainment. The results of the analysis were consistent with the assumption of an autosomal dominant mode of inheritance.

Adult↗

Pharmacokinetic studies of oral L-threo-3,4-dihydroxyphenylserine in normal subjects and patients with familial amyloid polyneuropathy.

The pharmacokinetics of oral L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) was studied in 7 normal subjects and 7 patients with familial amyloid polyneuropathy. Each person swallowed a single 300 mg dose in the fasting state, and L-threo-DOPS in plasma and urine was determined by high performance liquid chromatography with an electrochemical detector after separation on a boric acid gel column. L-threo-DOPS was slowly absorbed by normal subjects; the maximum plasma concentration occurred 3 h after administration and 20% of the oral dose was recovered unchanged in the urine within 12 h. It induced a substantial elevation of plasma norepinephrine levels, the peak being attained at 5 h, but without any change in blood pressure. In the patients, the absorption and metabolism of L-threo-DOPS were delayed, and a prolonged pressor response was observed, with a peak after 8 h. It was concluded that the effects on plasma norepinephrine and blood pressure of oral L-threo-DOPS were essentially equal to those of twice as large a dose of DL-threo-DOPS.

Adult↗

Orthostatic hypotension in familial amyloid polyneuropathy: treatment with DL-threo-3,4-dihydroxyphenylserine.

We measured plasma norepinephrine levels in patients with familial amyloid polyneuropathy. Patients with orthostatic hypotension had low basal plasma norepinephrine levels, which did not increase after postural change. On the basis of biochemical findings that suggest depletion of peripheral norepinephrine, DL-threo-3,4-dihydroxyphenylserine, an immediate precursor of norepinephrine, was given orally. Six hundred mg of this drug induced substantial and sustained elevation of blood pressure for several hours, and plasma norepinephrine content increased. Daily administration for 4 weeks improved postural dizziness and syncope, and daily activity increased.

Adult↗