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Biomedical subjects

H Uzawa

Publications and source records attributed to H Uzawa.

At least 37 records · Page 2Linked to original sources

A kindred of familial combined hyperlipidemia (FCHL) with proband showing type V hyperlipoproteinemia.

A case of familial hyperlipidemia incidentally found through a 16 year-old high school girl with type V hyperlipoproteinemia and abdominal bouts consistent with this type of hyperlipemia is reported for the first time in Japan. The laboratory findings of the plasma of her father revealed typical hyperlipoproteinemia of type IIa. Nineteen of her 26 kindred were investigated. Type V was seen only in the proband, type IIa in father, paternal grandmother, two paternal aunts, and two paternal cousins, type IV in three paternal cousins. The serum apolipoprotein (apo A-I, A-II, B, C-II, C-III, and E) concentrations were determined by the single radial immunodiffusion technique. The apolipoprotein concentrations were not different from those of normolipidemic control subjects except for apo B, which was higher in the hyperlipidemic members, and apo C-II, C-III, and E, which were higher in the proband.

Adolescent↗

Effect of simultaneous infusion of a somatostatin analogue, insulin and glucose on serum triglycerides and blood glucose levels in man.

Nine non-diabetic, non-obese, normocholesterolemic normal male subjects with varied triglycerides levels were subjected to a simultaneous infusion test with a synthetic somatostatin analogue [des(Ala1, Gly2)-D-Trp8, D-Asn3, 14-somatostatin], insulin and glucose under ambulatory conditions. The levels of C-peptide reactivity, immunoreactive glucagon and growth hormone were reduced, and the level of immunoreactive insulin remained constant during the infusion. The blood glucose reached a constant value at 110-120 minutes (steady state blood glucose, SSBG) after the commencement of the infusion. The total cholesterol (TC) levels decreased slightly in the 30 minutes after the experiments were begun, and the triglycerides (TG) levels decreased gradually throughout the infusion period, due mainly to the reduction of very low density lipoprotein (VLDL). The most striking finding was the highly significant positive correlation (p less than 0.005, r = 0.868) between SSBG and the serum TG level prior to the infusion. These results indicate an important relationship between insulin sensitivity and serum TG level. High TG level may be regarded as one of the indices of insulin resistance.

Adult↗

Relationship between platelet phospholipase activity and plasma in ischemic heart disease.

Platelet phospholipase plays an important role in the metabolic responses of platelets to exogenous stimuli. The platelet phospholipase activity (PLA) was therefore studied in 38 patients with ischemic heart disease (IHD) and in 26 age-matched normal subjects who served as controls. The mean platelet PLA in the IHD group was 12.72 +/- 1.03 nmol/mg protein/30 sec which was significantly (p less than 0.005) higher than that of the normal controls (8.72 +/- 0.76). When they were classified into acute stage, such as unstable angina or acute myocardial infarction (AMI), and chronic stage, such as stable angina or old myocardial infarction (OMI), there was no significant difference between them. On the other hand, about two-fold activation of platelet PLA was observed in acute stage IHD, and 20-30% inhibition of it was demonstrated in chronic stage IHD following the addition of autologous plasma to washed platelet suspensions, suggesting that certain plasma factor(s) are responsible for such phenomena. In an attempt to identify these plasma factor(s), various substances such as serum albumin, high density lipoprotein, prostaglandin E1 (PGE1) and E2 (PGE2), and platelet activating factor were assessed by in vitro experiments. Only PGE1 and PGE2 revealed a significant effect on the platelet PLA. The relationship between plasma and platelet activity in terms of platelet PLA deserves attention since it varies according to the type and stage of IHD.

Angina, Unstable↗

[A case of iodide myxedema observed for 3 years under a low iodide diet--especially on the restoration of the mechanism of escape from the Wolff-Chaikoff effect].

A 47-year-old housewife was admitted to our hospital because of general fatigue and constipation suggesting hypothyroidism. For 3 years before admission, general fatigue, arrhythmia, dry skin, drowsiness, cold intolerance and hypermenorrhea occurred insidiously. She had habitually taken considerable amounts of seaweed every day, e.g. more than 50 g of " Kombu " for more than 5 years and at least 1 g of " Wakame " for 6 months. On admission, serum thyroxine (T4) was 1.3 micrograms/dl, serum triiodothyronine (T3) was 47 ng/dl, TSH was 132 microunits/ml, and 123I thyroidal uptake was 60% at 3 hr. and 75% at 24 hr. Anti-thyroglobulin hemagglutination antibodies and anti-thyroid microsomal hemagglutination antibodies were both negative. When seaweed was omitted from her diet, T4 rose to 6.3 micrograms/dl and T3 rose to 113 ng/dl, whereas TSH lowered to 11 microunits/ml in 2 weeks. The seaweed-free diet was continued and 4 months later, when she had become euthyroid, an open biopsy of the thyroid gland was carried out. Histological examination of the specimen revealed a marked colloid deposition without characteristic features of Hashimoto's disease. Five months after admission, with the daily administration of 100 mg potassium iodide (KI), the effects of inorganic iodide on thyroid function had begun to be seen. On the 16th day of the KI regimen, palpitation and tachycardia (pulse rate 160/min.) with multifocal ventricular premature beat appeared, and T4 on the 11th day was 5.9 micrograms/dl, which was clearly lower than the pretreatment level of 8.4 micrograms/dl. KI was discontinued on the 16th day, and one week after the withdrawal, T4, T3 and TSH all returned to the pretreatment level. For more than 3 years on a seaweed-free diet, she remained euthyroid without any thyroid regimen. To see the effects of inorganic iodide on thyroid function after this long period on a seaweed-free diet, KI was again administered. One hundred mg/day KI for 14 days followed by 200 mg/day for 21 days had virtually no effect on T4, T3 and free T4 and she remained well. None of the perchlorate discharge tests performed on 3 occasions during the 6 month period after the initiation of the seaweed-free diet showed a discharge.(ABSTRACT TRUNCATED AT 400 WORDS)

Female↗

Blocking 3-hydroxy-3-methylglutaryl coenzyme A reductase with ML-236B enhances the plasma cortisol response to adrenocorticotropin in patients with hypercholesterolemia.

The effect of ML-236B, a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on serum lipids and plasma cortisol responses to ACTH were studied in 11 hypercholesterolemic patients. Mean serum total cholesterol decreased significantly [279 +/- 57 (SD) mg/dl to 213 +/- 48 mg/dl], as did serum triglycerides (211 +/- 140 mg/dl to 166 +/- 125 mg/dl) and low density lipoprotein cholesterol (195 +/- 49 mg/dl to 139 +/- 47 mg/dl), after ML-236B treatment for 12 weeks in doses ranging from 15-60 mg/day. The mean basal plasma cortisol level was not changed after ML-236B treatment, but the mean absolute increment in plasma cortisol increased from 15.4 +/- 3.4 to 26.7 +/- 8.4 micrograms/dl (P less than 0.005) after treatment. These data demonstrate a new effect of a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase in human adrenal tissue.

Adrenocorticotropic Hormone↗

Hydrolysis of succinyl-trialanine p-nitroanilide by two enzymes associated with human high-density lipoproteins.

Succinyl-trialanine p-nitroanilide (Suc-Ala3-pNA), a synthetic substrate for the determination of elastase activity, was hydrolyzed in sequence by two enzymes that were found to be associated with human high-density lipoproteins. The enzymes involved in the sequence of reaction were separated by ion-exchange chromatography from apo-lipoprotein A-I and A-II, major apoproteins of high-density lipoproteins. One, designated as fraction MK, cleaves Suc-Ala3-pNA to succinyl-dialanine and alanine p-nitroanilide (Ala-pNA), and the other, designated as fraction U, cleaves Ala-pNA to alanine and p-nitroaniline. Fraction MK was inhibited by dithiothreitol, EDTA, and 1,10-phenanthroline, whereas fraction U was inhibited by 1,10-phenanthroline and bestatin. In addition to these findings, fraction MK also hydrolyzed 2,4-dinitrophenyl-prolyl-glutaminyl-glycyl-isoleucyl-alanyl-glycyl-glutaminyl- arginine (DNP-octapeptide), a specific substrate for the determination of vertebrate collagenase. Neither native elastin nor native collagen was hydrolyzed by a mixture of the two enzymes. Fraction U was very similar to aminopeptidase M with respect to its enzyme characteristics studied.

Humans↗

Physical fitness. Its contribution to serum high density lipoprotein.

The effects of exercise conditioning on serum high density lipoprotein cholesterol (HDL-C) were studied using 20 members of a regular joggers club and other healthy non-member subjects of varying degrees of habitual physical activity (253 males and 391 females). Both the HDL-C and HDL-C/serum total cholesterol (TC) levels were significantly higher with the 20 regular joggers than with the sedentary controls matched for age, TC, serum triglycerides (TG) and weight index (WI). A significant correlation was found between HDL-C/TC and the exercise conditioning value obtained by using the results of the 12-min performance test as an index among the non-member subjects. In order to ascertain the relative significance of exercise conditioning in influencing HDL-C/TC, a multiple regression analysis was conducted using HDL-C/TC as the variable criterion. The results showed that TG affected HDL-C/TC the most among both males and females, while exercise conditioning affected it second among males and fourth among females.

Adult↗

Studies on 75 g oral glucose tolerance in the inhabitants of Kumamoto Prefecture, Japan.

The authors assessed the prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) according to the 1980 National Diabetes Data Group (1980 NDDG) classification and diagnosis. Two hundred and sixty inhabitants [aged 50.9 +/- 9.6 years, male: female (M:F) = 90: 170] of five small rural towns in Kumamoto Prefecture (population 1.8 million) and 279 male members of western divisions of the Japanese Ground Self Defence Forces (SDF employees) living in Kumamoto, who had retired at the age 50 years were subjected to the 75 g oral glucose tolerance test (75 g OGTT) in association with routine clinical and laboratory examinations. In addition, the results of 50 g OGTT obtained in 1243 SDF members (aged 50 years, male) from 1977 to 1980 were included in this study, after their blood glucose concentrations were converted to those of 75 g OGTT according to the 1982 recommendations of the Japan Diabetic Society. The overall prevalence of DM was 2.7%, IGT 17%. Out of the 10 subjects found to have DM in the inhabitants of the 5 rural towns, 6 (M:F = 3:3) were 60 years of age or over and half of them were aware of their diabetes mellitus. None of the 8 cases of DM discovered among the SDF employees examined in 1981-1982 had any signs or symptoms of DM, whereas 3 were hypertensive, 2 were markedly obese and 4 were hypertriglyceridemic.

Adult↗

Tolbutamide effect on cultured human endothelial cells with special reference to platelet aggregation.

Since the UGDP report, there have been many discussions on tolbutamide in relation to arterial metabolism. In view of this, we investigated the effect of tolbutamide on endothelial cells using ADP-induced platelet aggregation. We followed Gimbrone's method of cell culture and after the addition of tolbutamide, a platelet aggregation test was performed. 100 microM tolbutamide showed no inhibitory effect on platelet aggregation, but 1 mM tolbutamide effected a 25% decrease in aggregation. These results suggest that tolbutamide does not inhibit prostacyclin synthesis of endothelial cells at conventional dosages.

Adenosine Diphosphate↗

Proteolytic digestion of human serum apolipoproteins by porcine pancreatic elastase.

We studied the proteolytic action in vitro of free and alpha 2-macroglobulin-bound porcine pancreatic elastase [EC 3.4.21.11] on the apolipoproteins of plasma: very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL). Polyacrylamide gel electrophoresis, isoelectric focusing and immunodiffusion tests of elastase-treated plasma lipoproteins revealed that apolipoprotein C-II and C-III polypeptides were more susceptible to elastase in free form than plasma apolipoproteins (A-I, A-II, B, and E). Elastase bound to alpha 2-macroglobulin did not show any such activities.

Animals↗

Unusual familial lipoprotein C-III associated with apolipoprotein C-III-O preponderance.

Among 256 consecutive subjects so far studied in our laboratory, we found one subject (a 63-year-old female) whose very low density lipoprotein (VLDL) and high density lipoprotein (HDL) contained unusually high amounts of apolipoprotein C-III-O among apolipoprotein C-III polymorphic forms. Identification of apolipoprotein C-III-O was achieved by a combination of basic polyacrylamide gel electrophoresis, isoelectric focusing and sialidase treatment of plasma apolipoproteins. This unusual lipoprotein was inherited by two of her four children without the manifestation of clinical symptoms. Triacylglycerols and cholesterol concentrations of VLDL, low density lipoprotein (LDL) and HDL fractions, and serum apolipoprotein C-III levels of the three subjects with apolipoprotein C-III-O were within the normal range, as estimated by rocket immunoelectrophoresis. Our results clearly demonstrated that the unusual lipoproteins with the preponderance of apolipoprotein C-III-O among apolipoprotein C-III polymorphic forms were genetically determined. These cases may be a new type of genetic lipoprotein disorder.

Adult↗

A case with glucagonoma syndrome--endocrine and metabolic studies.

The results of clinical endocrine and metabolic studies on a 57-year-old female with surgically and autopsy verified glucagonoma syndrome were presented. All of the clinical manifestations of glucagonoma syndrome so far reported in the literature were noted but there was no evidence indicating the presence of multiple endocrine adenomatosis. The plasma IRG level was always more than 20 times above the normal, and the IRG response to insulin and tolbutamide injection was abnormal and the results of the other endocrinological studies revealed less remarkable features, if any. The surgically removed metastatic tumor of the liver contained an enormous amount of IRG and an appreciable amount of IRI, indicating that the elevated plasma IRG was mainly of tumor origin. These results clearly indicate that in glucagonoma there is some abnormality in glucagon release from the tumor. In addition to these findings, hypocalcemia, cardiac left ventricular hypertrophy and gastrointestinal dysfunction reportedly due to hyperglucagonemia were also seen in this patient.

Adenoma, Islet Cell↗

A case with glucagonoma syndrome--heterogeneity of glucagon and insulin.

The heterogeneity of glucagon and insulin in plasma and tissue extracts from a 57-year-old female with glucagonoma syndrome with surgically and autopsy verified islet-cell tumors was studied by Bio-Gel P-10 filtration. The preoperative plasma immunoreactive glucagon (IRG) level was 20.2 ng/ml, and plasma glucagon-like immunoreactivity(GLI) 25.8 ng/ml. The column chromatography of the preoperative plasma revealed three or four IRG components and four GLI components. Among these, peak II, the large glucagon immunoreactivity (LGI) peak, considered a candidate for proglucagon, was prominent, along with peak III. The resected metastatic liver tumor contained an enormous amount of IRG and an appreciable amount of immunoreactive insulin (IRI), indicating that the elevated plasma IRG was mainly of tumor origin. The IRG pattern of the tumor tissue extract revealed a small quantity of IRG in peaks I and II, and a large amount in peak III; control pancreatic tissue extract manifested a similar elution pattern. The IRI elution pattern of the tumor tissue extract revealed two major IRI peaks which migrated close to the elution volume of cytochrome C and insulin, respectively. This is a quite different pattern from the control pancreatic tissue extract in which the RI peak was localized in the elution volume of the insulin. We conclude that the present metastatic liver tumor produced not only enormous amounts of glucagon but heterogeneous peptides which contained immunological insulin determinants within their.

Adenoma, Islet Cell↗