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Biomedical subjects

I Mineo

Publications and source records attributed to I Mineo.

At least 37 records · Page 2Linked to original sources
PubMed1990

Glucose infusion abolishes the excessive ATP degradation in working muscles of a patient with McArdle's disease.

A 23-year-old woman with McArdle's disease performed mild leg exercise on a bicycle ergometer. Saline or 10% glucose solution was infused throughout exercise. After exercise with saline infusion, her plasma concentrations of ammonia, hypoxanthine and creatine kinase increased greatly. Conversely, after exercise with glucose infusion, there were no appreciable changes in these plasma substances. In addition, she noticed that glucose infusion relieved her from muscle symptoms during exercise. These findings suggest that glucose infusion to patients with McArdle's disease ameliorates excessive ATP degradation in exercising muscles.

Adenosine Triphosphate↗
PubMed1990

A novel pathway for alternative splicing: identification of an RNA intermediate that generates an alternative 5' splice donor site not present in the primary transcript of AMPD1.

AMP deaminase (AMPD) is a central enzyme in eucaryotic energy metabolism, and tissue-specific as well as stage-specific isoforms are found in many vertebrates. This study demonstrates the AMPD1 gene product in rat is alternatively spliced. The second exon, a 12-base miniexon, was found to be excluded or included in a tissue-specific and stage-specific pattern. This example of cassette splicing utilizes a unique pathway through an RNA intermediate that generates an alternative 5' splice donor site at the point where exon 2 is ligated to exon 1. In the analogous intermediate of human AMPD1, the potential 5' splice donor site created at the boundary of exon 1 and exon 2 was a poor substrate for splicing because of differences in exon 2 sequences, and human AMPD1 was not alternatively spliced. These results demonstrate that in some cases alternative splicing may proceed through an RNA intermediate that generates an alternative splice donor site not present in the primary transcript. Discrimination between alternative 5' splice donor sites in the RNA intermediate of AMPD1 is apparently controlled by tissue-specific and stage-specific signals.

AMP Deaminase↗
PubMed1989

Autoantibodies to the insulin receptor impair clearance of plasma endogenous insulin.

Plasma insulin clearance was studied in a patient with autoantibodies to the insulin receptor, manifesting persistent hyperinsulinemia associated with alternating hyper- and hypoglycemia. In the postabsorptive period, the plasma glucose level gradually decreased. To prevent the development of hypoglycemia, glucose was infused and the glycemic level was clamped at 50 mg/dl without insulin infusion. The plasma C-peptide level was below the detectable range during the clamp, indicating no appreciable secretion of insulin. The plasma insulin level declined exponentially with a markedly prolonged disappearance rate (half-time: 3.0 h) during the study. These results indicate that hyperinsulinemia in the postabsorptive period in this patient is attributable to the impairment of plasma insulin clearance through receptor-mediated mechanisms, and also confirm that the receptor plays the principal role in plasma insulin removal.

Acanthosis Nigricans↗
PubMed1989

Hyperinsulinemia due to impaired insulin clearance associated with fasting hypoglycemia and postprandial hyperglycemia: an analysis of a patient with antiinsulin receptor antibodies.

Antiinsulin receptor antibodies were detected in the serum of a patient with insulin-resistant diabetes. Fasting hypoglycemia and postprandial hyperglycemia recurred every day. The plasma insulin level was 553 +/- 359 pmol/L [77 +/- 50 microU/mL (mean +/- SD)] in the fasting state and rose above 7500 pmol/L postprandially. The glycemic clamp at 2.8 mmol/L (50 mg/dL) without insulin infusion revealed that the half-life of plasma endogenous insulin was 173 min, indicating severely impaired plasma insulin clearance. During the clamp the glucose infusion rate was almost constant (0.9-1.2 mg/kg.min) despite an exponential decline in the plasma insulin level from 460 pmol/L (65 microU/mL) to 129 pmol/L (18 microU/mL). Intravenous insulin administration did not appreciably accelerate the basal constant decrease in the plasma glucose level during the postabsorptive period. These results indicate the coexistence of marked insulin resistance and constant ability to decrease plasma glucose level. In in vitro experiments, antireceptor immunoglobulin G from this patient increased the fructose 2,6-bisphosphate concentration in the presence of glucagon (less than 0.1 nmol/L) in primary cultured rat hepatocytes. The antireceptor immunoglobulin G stimulated autophosphorylation of rat liver insulin receptor. We conclude that antiinsulin receptor antibodies could impair plasma insulin clearance, resulting in persistent hyperinsulinemia, and that continuous receptor stimulation by the antibodies was responsible for the development of hypoglycemia.

Animals↗
PubMed1988

Transcatheter arterial chemo-embolization for humoral hypercalcemia of hepatocellular carcinoma.

A 50-year-old male with unresectable hepatocellular carcinoma (HCC) had a hypercalcemic crisis with a serum calcium concentration of 7.8 mEq/zeta, without any evidence for bone metastases or parathyroid lesions. The hypercalcemia was thought to be due to increased renal reabsorption of calcium and increased bone resorption, which was probably caused by humoral factors derived from the HCC, some being parathyroid hormone-like factors. Since conservative therapy for hypercalcemia was not sufficiently effective and was accompanied by progressive exacerbation of ascites and leg edema, transcatheter arterial chemo-embolization (TACE) was performed. On the following day, serum calcium concentration decreased from 6.3 mEq/zeta to the normal range, although serum alpha-fetoprotein levels decreased only slightly. Thereafter hypercalcemia did not develop for about 4 weeks. The results demonstrated that TACE can be effective for humoral hypercalcemia of HCC.

Carcinoma, Hepatocellular↗
PubMed1988

Increases in hepatic fructose-2,6-bisphosphate level and fructose-6-phosphate,2-kinase activity in rats with ventromedial lesions of the hypothalamus.

To investigate altered fructose-2,6-bisphosphate (fructose-2,6-P2) metabolism, we measured fructose-2,6-P2 levels and fructose-6-phosphate,2-kinase (fructose-6-P,2-kinase) activities in various tissues, including liver, kidney, heart, and skeletal muscle, of ventromedial hypothalamus (VMH)-lesioned rats during feeding and starvation. The plasma insulin level was 6 times or more higher in these rats than in the controls. The fructose-2,6-P2 level in liver was much greater in VMH-lesioned rats than in the controls: 15.1 +/- 2.2 nmol/g tissue versus 7.7 +/- 0.7 in the fed state, 5.3 +/- 1.1 versus 1.6 +/- 0.4 in the starved state. In kidney, heart, and skeletal muscle, fructose-2,6-P2 levels were not different between the two animal groups. The activity of hepatic fructose-6-P,2-kinase remained high after 20 h of starvation in VMH-lesioned rats, whereas it was decreased markedly in the controls. The hepatic concentration of fructose-6-phosphate was also high in VMH-lesioned rats. Both fructose-6-P,2-kinase activity and fructose-6-phosphate concentration in the liver of starved VMH-lesioned rats were comparable to those of control rats in fed conditions. These results indicate that the alteration of fructose-2,6-P2 metabolism is characteristic of liver in VMH-lesioned rats, and that the increase in hepatic fructose-2,6-P2 may activate hepatic glycolysis not only during feeding but also during starvation, leading to the enhanced lipogenesis in these obese rats.

Animals↗
PubMed1988

Exaggerated insulin secretory response in patients with insulinomas to midaglizole, a drug with alpha 2-adrenergic blocking activity.

Midaglizole is a new alpha 2-adrenergic blocking agent which increases insulin release from normal pancreatic islets. We studied its effect in four patients with insulinomas. In three patients oral administration of 150 mg of midaglizole caused a large increase in serum insulin and a corresponding decrease in plasma glucose. The magnitude of the response cannot exclude the possibility that midaglizole has direct beta cell stimulatory activity. Two of the three patients had operations, and their insulin responses to midaglizole became normal after removing the tumours. In contrast, midaglizole did not stimulate insulin secretion in the fourth patient. A midaglizole stimulation test might be useful in screening patients with insulinomas.

Adenoma, Islet Cell↗
PubMed1988

Erythrocyte glycolysis and its marked alterations by muscular exercise in type VII glycogenosis.

Levels of erythrocyte glycolytic intermediates after the phosphofructokinase (PFK) step, including 2,3-bisphosphoglycerate (2,3-DPG), were decreased at rest in patients from separate families with type VII glycogenosis. The concentration of 2,3-DPG was about half of the normal control value during a period of unrestricted daily activity but was further decreased to one third of normal after a one-day bed rest. Mild ergometric exercise rapidly increased the levels of fructose-1,6-bisphosphate, dihydroxyacetone phosphate plus glyceraldehyde-3-phosphate, and 2,3-DPG in patients' circulating erythrocytes but did not in those of normal subjects. This indicated that a crossover point at the PFK step in glycolysis disappeared after physical exercise and, consequently, the 2,3-DPG concentration, which had decreased because of blockage of the PFK step, was restored considerably. This apparently exercise-related alteration in intermediary metabolism at the beginning of glycolysis was reproduced in vitro by incubating normal erythrocytes in the presence of inosine or ammonia, both of which have increased levels in circulating blood during and after exercise in this disorder. We conclude that physical activity in addition to a genetic deficiency in erythrocyte PFK affects glycolysis in erythrocytes in type VII glycogenosis and that myogenic factors released from exercising muscles may be responsible for this change.

2,3-Diphosphoglycerate↗
PubMed1988

Inosine and adenosine formation in ischemic and non-ischemic contracting muscles of rats: difference between fast and slow muscles.

Inosine and adenosine formation was evaluated in different types of rat skeletal muscle during ischemic and non-ischemic contraction. Extensor digitorum longus (EDL, fast) and soleus (slow) muscles were stimulated electrically via the sciatic nerve (5 Hz, 10 min). Under non-ischemic condition, the concentrations of IMP, inosine, adenosine, and hypoxanthine increased in EDL muscles but not in soleus muscles during stimulation. Under ischemic condition, these metabolites increased in both EDL and soleus muscles, although the increases in IMP and inosine were greater in EDL muscles. The increase in inosine had a strong positive correlation with that in IMP in ischemic EDL and soleus muscles, but the ratio, delta inosine/delta IMP was smaller in EDL muscles. The increase in adenosine under ischemic condition was not significantly different between the two muscles. These findings suggest that ischemia enhances degradation of purine nucleotides in contracting fast and slow muscles, and that although the degradation of purine nucleotides to IMP is greater in fast muscles than in slow muscles, the relative degradation rate of IMP to inosine is rather smaller in fast muscles.

Adenosine↗
PubMed1987

Myogenic hyperuricemia. A common pathophysiologic feature of glycogenosis types III, V, and VII.

To identify the mechanism of hyperuricemia in glycogen storage diseases (glycogenoses) that affect muscle, we studied the effects of exercise and prolonged rest on purine metabolism in two patients with glycogenosis type III (debrancher deficiency), one patient with type V (muscle phosphorylase deficiency), and one patient with type VII (muscle phosphofructokinase deficiency). All had hyperuricemia except for one patient with glycogenosis type III. Plasma concentrations of ammonia, inosine, and hypoxanthine increased markedly in all the patients after mild leg exercise on a bicycle ergometer. The plasma urate concentrations also increased, but with a delayed response. Urinary excretion of inosine, hypoxanthine, and urate increased greatly after exercise, consistently with the increases in plasma levels. Hypoxanthine and urate concentrations were extremely high in the plasma and urine of the patient with glycogenosis type VII. With bed rest, the plasma hypoxanthine level returned to normal within a few hours, and the plasma urate concentration decreased from 18.6 to 10.6 mg per deciliter (1106 to 630 mumol per liter) within 48 hours. Similarly, the urinary excretion of these purine metabolites was reduced by bed rest. These findings indicate that muscular exertion in patients with glycogenosis types III, V, and VII causes excessive increases in blood ammonia, inosine, and hypoxanthine due to accelerated degradation of muscle purine nucleotides. These purine metabolites subsequently serve as substrates for the synthesis of uric acid, leading to hyperuricemia.

Adult↗
PubMed1987

Enhanced release of ammonia and hypoxanthine from exercising muscles in patients with idiopathic hypoparathyroidism.

Semiischemic forearm exercise tests were carried out in two patients with idiopathic hypoparathyroidism who had muscle cramps and high serum levels of creatine kinase. Although cubital venous lactate levels increased normally after forearm exercise, venous ammonia and hypoxanthine were greatly increased. The abnormal responses of ammonia and hypoxanthine were normalized 3 months after treatment with 1 alpha-hydroxyvitamin D3. These findings suggest that excess purine degradation occurred in exercising muscles of patients with idiopathic hypoparathyroidism.

Adult↗