Biomedical subjects

T Mokuno

Publications and source records attributed to T Mokuno.

13 recordsLinked to original sources

PubMed1999

Glucose transporter 2 concentrations in hyper- and hypothyroid rat livers.

The deterioration of glucose metabolism frequently observed in hyperthyroidism may be due in part to increased gluconeogenesis in the liver and glucose efflux through hepatocyte plasma membranes. Glucose transporter 2 (GLUT 2), a facilitative glucose transporter localized to the liver and pancreas, may play a role in this distorted glucose metabolism. We examined changes in the levels of GLUT 2 in livers from rats with l-thyroxine-induced hyperthyroidism or methimazole-induced hypothyroidism by using Western blotting to detect GLUT 2. An oral glucose tolerance test revealed an oxyhyperglycemic curve (impaired glucose tolerance) in hyperthyroid rats (n=7) and a flattened curve in hypothyroid rats (n=7). GLUT 2 levels in hepatocyte plasma membranes were significantly increased in hyperthyroid rats and were not decreased in hypothyroid rats compared with euthyroid rats. The same results were obtained with a densitometric assay. These findings suggest that changes in the liver GLUT 2 concentration may contribute to abnormal glucose metabolism in thyroid disorders.

Animals↗

PubMed1997

Recombinant human TSH receptor expressed in E. coli.

We expressed the extracellular domain (20-408 aa, (T) of human TSH receptor (TSHR) in E. coli to detect TSHR autoantibodies (TRAb) and, moreover, we expressed the two portions (20-218 aa (5') and 217-408 aa (3')) of the extracellular domain thought to distinguish thyroid stimulating antibodies (TSAb) from blocking antibodies (TSBAb), using pGEX.3X as the expression vector. Using Western blotting analysis of the sera from patients with autoimmune thyroid disease, sera from Graves' patients and patients with idiopathic myxedema who had TSBAb reacted with the fusion protein (T), but none of the control sera reacted with it. We further evaluated whether or not the positive sear for T recognized fusion proteins (5') or (3'). The sera from Graves' patients reacted with both fusion proteins (5') and (3'). The sera from patients with idiopathic myxedema did not react with either of fusion proteins (5') or (3'). These findings suggest that these recombinant TSHR proteins could be used as antigens to detect TRAb, and differentiate TSABb from patients with idiopathic myxedema.

Antibodies, Blocking↗

PubMed1997

Alteration of platelet aggregation in patients with thyroid disorders.

To determine whether Graves' disease or primary hypothyroidism influence platelet function, we evaluated platelet aggregation in the platelet-rich plasma (PRP) from such patients. Platelet aggregation induced by adenosine diphosphate (ADP) in blood obtained from patients with untreated Graves' disease was significantly lower than normal, whereas that in patients with untreated primary hypothyroidism was relatively increased. The magnitude of platelet aggregation induced by collagen in both groups of patients resembled that induced by ADP. However, significant differences were evident between the two diseases (P < .05). In addition, we observed a significant inverse correlation between the extent of platelet aggregation and plasma levels of thyroid hormones (triiodothyronine [T3], thyroxine [T4], and free T3). Platelet aggregation returned to normal when the euthyroid condition was obtained in the patients following administration of antithyroid drugs or thyroid hormone. The findings are consistent with the possibility that thyroid hormones influence platelet aggregation partly via inhibition of myosin light-chain kinase (MLCK).

Adenosine Diphosphate↗

PubMed1996

Short stature due to growth hormone deficiency associated with Cushing's disease and ulcerative colitis.

We report a rare case of Cushing's disease associated with ulcerative colitis in a patient primarily treated with growth hormone due to short stature. At the age of fifteen years, the patient had a short stature due to GHD and was treated with the extracted GH for a short period. At the age of twenty-one years, his body weight gradually increased and, based on the results of several tests, he was diagnosed with Cushing's disease and GHD was observed in our patient. The excess secretion attenuation of pituitary hormones with reduced secretion periods as well as the relation between ulcerative colitis and elevated plasma cortisol concentrations is briefly discussed in this paper.

Adult↗

PubMed1996

A case of myocarditis associated with IDDM.

We report a case of diabetic ketoacidosis (DKA) complicated by acute myocarditis, which was confirmed by cardiac biopsy. A 26-year-old man was hospitalized with severe DKA. On admission, nonspecific ST-T change was noted on the electrocardiogram (ECG). The patient's levels of creatine phosphokinase (CPK) and glutamic oxaloacetic transaminase were slightly elevated, but he did not complain of chest discomfort or symptoms of heart disease. On the first day after admission, ST-T elevation was noted on ECG during treatment of DKA. By cardiac angiography and cardiac biopsy, coronary heart disease was ruled out and postmyocarditic change was histologically confirmed. An episode of upper respiratory viral infection before the onset of acute diabetes suggested that the patient suffered from viral-induced myocarditis and consequent development of IDDM. This possibility was confirmed by the clinical course of ECG change, with elevated CPK and lactate dehydrogenase and a slightly elevated antibody titer for echovirus.

Adult↗

PubMed1995

[A rare case of a diabetic patient with small cell lung cancer, initially diagnosed as pyogenic vertebral osteomyelitis].

A rare case of a patient with non-insulin-dependent diabetes mellitus (NIDDM) with small cell lung cancer, initially diagnosed as pyogenic vertebral osteomyelitis, was reported. A 40-year-old male patient was diagnosed with NIDDM about 3 years earlier, but he did not receive any treatment. Then, a two-month history of high fever, persistent cough and back pain developed. Chest X-ray film showed a lung infiltrate with a small cavity in the upper portion of the left lung. Computed tomography and magnetic resonance imaging of the chest revealed a tumor mass shadow with osteoclasia along the bodies of the 6th and 7th thoracic vertebral bone. Staphylococcus aureus infection was confirmed by arterial blood culture. Administration of antibiotics resulted in the disappearance of the left lung infiltrate and a slight reduction of the tumor mass in the thoracic vertebral bone, suggesting pyogenic vertebral osteomyelitis as an unusual complication of NIDDM. However, as the tumor mass still remained, needle biopsy for the mass lesion was performed, resulting in the diagnosis of metastasis of small cell carcinoma from the left lung. Gene aberration in this lung disease has been reported recently, and its correlation with NIDDM which may also be induced by genetic abnormality is an interesting question that remains to be resolved.

Adult↗

PubMed1995

Dexamethasone-induced changes in glucose transporter 4 in rat heart muscle, skeletal muscle and adipocytes.

To clarify the effect of glucocorticoid on glucose transporters (GLUT) in adipocytes and muscle, we examined the changes of GLUT4 in rat heart muscle, skeletal muscle and adipocytes during long-term administration of dexamethasone and the translocation of GLUT4. The levels of GLUT4 in the plasma membrane and the low-density microsome fraction were measured by Western blotting using anti-GLUT4 peptide antibody. The levels of GLUT4 in the heart and skeletal muscles of rat were unchanged by treatment of dexamethasone. In the adipocytes the level of GLUT4 in plasma membrane was changed, but it was decreased in the low-density microsome fraction. Although adipocytes are less involved in blood sugar regulation than skeletal muscle, this finding suggests that glucose metabolism in Cushing's syndrome is affected partly by a decrease of GLUT4 in the adipocytes.

5'-Nucleotidase↗

PubMed1995

Effects of thyroid hormone on coenzyme Q and other free radical scavengers in rat heart muscle.

Active oxygen species are reported to cause organ damage. This study was therefore designed to determine the behaviour of antioxidants and free radical scavengers so as to reveal changes in animals in the hyper- and hypothyroid state. Levels of antioxidant factors (i.e. coenzyme Q (CoQ)10, CoQ9 and vitamin E) and free radical scavengers (catalase, glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD)) were measured in the heart muscles of rats rendered hyper- or hypothyroid by 4 weeks of thyroxine (T4) or methimazol treatment. Serum levels of CoQ9 and total SOD were also measured. A significant reduction in CoQ9 levels was observed in the heart muscles of both hyper- and hypothyroid rats when compared with control hearts. There was no difference in serum CoQ9 levels in thyroid dysfunction when compared with control animals. Levels of vitamin E in the heart muscles of hyperthyroid rats were significantly increased, and there was no reduction in vitamin E levels in hypothyroid rats when compared with control hearts. GSH-PX levels in the heart muscle were reduced in hyperthyroid rats and increased in hypothyroid rats when compared with control hearts. However, there were no differences in catalase levels in heart muscle between hyper- and hypothyroid rats. The concentration of SOD in heart muscle was increased in hyperthyroid rats and was not decreased in hypothyroid rats compared with control rats, suggesting the induction of SOD by excessive production of O2-. These data suggest that the changes in these scavengers have some role in cardiac dysfunction in the hyper- and hypothyroid state in the rat.

Animals↗

PubMed1995

Changes in calmodulin concentration and cyclic 3',5'-nucleotide phosphodiesterase activity in skeletal muscle of hyper- and hypothyroid rats.

Hyper- and hypothyroid states occasionally induce skeletal muscle dysfunction i.e. periodic paralysis and thyroid myopathy. The etiology of these diseases remains unclear, but several findings suggest that the catecholamine-beta-receptor-cAMP system or other messenger systems are disturbed in these diseases. In this context, we evaluated changes in the cyclic 3',5'-nucleotide metabolic enzyme, cyclic 3',5'-nucleotide phosphodiesterase (PDE) and calmodulin concentrations in skeletal muscles of hyper- and hypothyroid rats. Activities of cyclic AMP-PDE were low in skeletal muscle both from hyper- and hypothyroid rats, and calmodulin concentration was high in hyperthyroid and low in hypothyroid rats, as compared with normal rats. DE-52 column chromatographic analysis showed that the cGMP hydrolytic activity in peak I and the cAMP hydrolytic activity in peak II were decreased in hypothyroid rats, whereas cAMP hydrolytic activity in peak III was unchanged. The cAMP hydrolytic activity in peak III was decreased in hyperthyroid rats, but the activities in peaks I and II were unchanged. These findings indicate that cAMP and calmodulin may have some role in skeletal muscle function in the hyperthyroid state, and that cAMP and calmodulin-dependent metabolism may be suppressed in the hypothyroid state.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1994

Immunoreactive creatine kinase-MB and creatine kinase isozyme concentrations during treatment of hypothyroid patients.

Using a highly sensitive enzyme immunoassay (EIA) system, we determined creatine kinase isozymes, namely creatine kinase-MB and creatine kinase-MM, in sera of patients suffering from primary hypothyroidism with concomitant signs of myocardial affections before and during treatment. After oral administration of L-thyroxine, the augmented mass concentrations of serum creatine kinase-MB and creatine kinase-MM, and the increased catalytic activity concentrations of serum total creatine kinase and creatine kinase-MB gradually decreased in inverse proportion to the increased concentrations of serum triiodothyronine (T3) and thyroxine (T4). By the 6th to 8th week after treatment, the elevated levels of serum total creatine kinase and creatine kinase-MB catalytic activity concentrations (assayed by a routine method) and serum creatine kinase-MM mass concentrations (assayed by EIA) declined to normal values, while serum T3, T4, and thyroid stimulating hormone attained normal values. Serum creatine kinase-MB mass concentrations (assayed by EIA), however, still remained at the higher level, without complete recovery from myocardial damage, as shown by electrocardiogram (ECG). These data indicate that metabolic distortion still exists in the myocardium, as revealed by the high creatine kinase-MB mass concentration, especially as assayed by EIA, even though the plasma levels of thyroid hormones had returned to normal.

Aged↗

PubMed1994

Changes of calmodulin concentration and cyclic 3',5'-nucleotide phosphodiesterase activities in cardiac muscle of hyper- and hypothyroid rats.

To investigate the effect of thyroid hormone on cardiac muscle dysfunction in hyper- and hypothyroid states, we evaluated cyclic 3',5'-nucleotide metabolism by measuring cyclic 3',5'-nucleotide phosphodiesterase activity and calmodulin concentrations in the cardiac muscles of hyper- and hypothyroid rats. Cyclic AMP (cAMP) concentration was significantly high in the cardiac muscle of hyperthyroid rats and low in that from hypothyroid rats compared with control rats. Cyclic AMP and cyclic GMP phosphodiesterase activities were significantly decreased in the soluble fraction of cardiac muscle from hyperthyroid rats and markedly increased in this fraction in hypothyroid rats compared with normal animals. Calmodulin concentration was high in hyperthyroid and low in hypothyroid rats. It was concluded from these findings that low cAMP-phosphodiesterase activity might, in part, bring about the high concentration of cAMP. Calmodulin was significantly high in the cardiac muscle of hyperthyroid rats and the reverse was the case in hypothyroid rats compared with normal rats. The implication is that, in hyper- and hypothyroid states, these changes may play an important role in cardiac function via their effect on cyclic nucleotide and Ca2+ metabolism.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1994

Bilateral ptosis with ophthalmoplegia in a 72-year-old woman with diabetes.

Ophthalmoplegia is common cranial neuropathy of Diabetes. In case of 3rd nerve involvement, usually unilateral extra ocular muscles are affected. However, ptosis is very rare in patients with diabetic neuropathy. In this report, we describe bilateral ptosis with ophthalmoplegia in diabetes. In ophthalmoplegia associated with diabetes, ischemic nerve infarction was reported. We treated this patient with Lipo prostaglandin (PG) E1. Since then, increased platelet aggregation activity was found in this patient. After two months, the symptoms of this patient were improved.

Aged↗

PubMed1993

Vertebral bone metastasis of small cell carcinoma of lung in a diabetic patient, initially diagnosed as pyogenic vertebral osteomyelitis.

A 40-year-old man with a 3-year history of uncontrolled NIDDM, 2-pack/month cigarette smoking habit and alcohol abuse, was admitted to our university hospital. He presented with severe back pain, persistent cough and fever. A left lung infiltrate was noted on chest X-ray film. Staphylococcus aureus was isolated from arterial blood. Thoracic bone destruction with pleural mass lesion confirmed by computed tomography (CT) and magnetic resonance image (MRI). These findings mislead our diagnosis to pyogenic osteomyelitis associated with NIDDM. An absence of marked clinical and roentgenological improvement after antibiotic therapy and strict glycemic control with insulin was noted. This suggested to us the need for needle biopsy of the osteolytic and mass lesions confirmed by imaging techniques. This resulted in making the diagnosis of metastasis of small cell carcinoma from the left lung. The correlation between NIDDM and pulmonary small cell carcinoma possibly induced by genetic abnormality remains to be resolved. By making the most of imaging techniques and needle biopsy, the possibility of pulmonary small cell carcinoma complicating NIDDM can be appropriately evaluated.

Adult↗