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Biomedical subjects

A Nakai

Publications and source records attributed to A Nakai.

At least 163 records · Page 9Linked to original sources
PubMed1988

DNA polymerase beta in human thyroid of Graves' disease and thyroid tumors.

We have shown that the level of DNA polymerase beta of rat adrenal cortex is regulated by pituitary trophic hormones and may correlate with their endocrine function. Here we measured DNA polymerase beta activity in human thyroid tissues of various benign and malignant thyroid disorders in order to verify the correlation between DNA polymerase beta activity and endocrine function. In Graves' disease (hyperfunction), the level of DNA polymerase beta per cell was three times higher than in normal thyroid, while in undifferentiated thyroid carcinomas this enzyme level was lower than normal. Furthermore, DNA polymerase beta in the crude extracts of cancer cells showed larger molecular forms, ranging from five to 12S, upon sucrose gradient sedimentation. These observations further support the hypothesis that the activity of DNA polymerase beta correlates, in part, with the functional level of the endocrine organ and with cell differentiation.

Adenoma↗
PubMed1988

Characterization of a thyroid hormone receptor expressed in human kidney and other tissues.

A cDNA encoding a specific form of thyroid hormone receptor expressed in human liver, kidney, placenta, and brain was isolated from a human kidney library. Identical clones were found in human placenta and HepG2 cDNA libraries. The cDNA encodes a 490-amino acid protein (Mr, 54,824). When expressed and translated in vitro, the protein product binds triiodothyronine with Ka of 2.3 X 10(9) M-1. This protein, designated human thyroid hormone receptor type alpha 2 (hTR alpha 2), has the same domain structure as other members of the v-erbA-related superfamily of receptor genes. It is similar to thyroid hormone receptor type alpha described in chicken and rat and less similar to human thyroid hormone receptor type beta (formerly referred to as c-erbA beta) from placenta. However, it is distinguished from these receptors by an extension of the C-terminal hormone binding domain making it 80 amino acids longer than rat thyroid hormone receptor type alpha 1 [Thompson, C.C., Weinberger, C., Lebo, R. & Evans, R. M. (1987) Science 237, 1610-1614]. Different sizes of mRNA found in liver (2.5 kilobases) and kidney (2 kilobases) suggest there may be tissue-specific processing of the primary transcript of this gene. Identification of human thyroid hormone receptor type alpha 2 indicates that two or more forms of thyroid hormone receptor exist in human tissues and may explain the normal variation in thyroid hormone responsiveness of various organs and the selective tissue abnormalities found in the thyroid hormone resistance syndromes.

Amino Acid Sequence↗
PubMed1988

Characterization of a third human thyroid hormone receptor coexpressed with other thyroid hormone receptors in several tissues.

A cDNA that encodes a third type of human thyroid hormone receptor (hTR alpha 1) has been isolated from a skeletal muscle library. The cDNA encodes a 410 amino acid protein, Mr = 46,820. When expressed and translated in vitro, hTR alpha 1 binds T3 with an association constant (ka) of 1.8 x 10(9) M-1. Comparison of the DNA sequence of hTR alpha 1 and a previously identified alpha type thyroid hormone receptor (hTR alpha 2) suggests that they could be transcribed from the same gene, and that alternative RNA splicing results in the synthesis of either hTR alpha 1 or hTR alpha 2. Two mRNA (3.2 kilobases and 6 kilobases) of hTR alpha 1 have been detected in several tissues. At least three types of thyroid hormone receptors (hTR alpha 1, alpha 2, beta), which possess similar affinities for hormone ligands, can be expressed in the same tissue.

Amino Acid Sequence↗
PubMed1988

Hormonal regulation of DNA polymerase-beta activity in the rat thyroid gland.

Using hypophysectomized rats, it has been shown that DNA polymerase-beta activity in the adrenal gland and testis is largely influenced by pituitary trophic hormones. Sucrose gradient centrifugation of thyroid extracts revealed three peaks of DNA polymerase-beta activity sedimenting at 3.3S, 7.3S and 12S. Of these, hypophysectomy induced a decrease in the 3.3S DNA polymerase-beta, whereas other molecular forms were affected only slightly. DNA polymerase-alpha and -gamma activities were unaffected by hypophysectomy. These changes in DNA polymerase-beta caused by hypophysectomy were reversed by daily i.p. injection of TSH. Furthermore, stimulation of the thyroid by excess TSH induced by the administration of 1-methyl-2-mercaptoimidazole resulted in an increase of all forms of thyroid DNA polymerase-beta. These results show that the level of DNA polymerase is relatively constant after hypophysectomy but that DNA polymerase-beta in the rat thyroid gland is also modulated by TSH mainly through the change of activity of the polymerase-beta which sediments at 3.3S.

Animals↗
PubMed1987

[Change in serum thyroid hormone levels in patients with acute myocardial infarction].

It has been reported that there is a decrease in the serum concentration of thyroid hormones in non-thyroidal illness. In the present study we made serial measurements of serum concentration of thyroid hormones [triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), reverse triiodothyronine (rT3)], thyroid stimulating hormone (TSH) and thyroxine binding globulin (TBG) in 10 patients with acute myocardial infarction (AMI, Grade I, according to the classification of Killip & Forrester) during 14 days after onset. In the early phase of AMI, serum T3, T4, FT3 and FT4 levels decreased while rT3 increased. TSH and TBG levels, however, were unchanged. In the patients with a high peak creatine phosphokinase activity (greater than or equal to 400 mU/ml), the decrease in thyroid hormone and increase in serum rT3 levels were greater than in patients with a low peak value (less than 400 mU/ml), suggesting a correlation between severity of AMI and changes in serum thyroid hormone levels. Especially, serum FT3 levels fell below the lower limit of controls within 14 days, with the lowest levels and the rT3 peak on the third day after onset. These data suggest that in AMI peripheral conversion of T4 favours rT3 production and that low levels of serum FT3 and T3 protect the infarcted heart muscle against thyroid hormone action.

Aged↗
PubMed1987

Increase in S-100b protein content in thyroid carcinoma.

S-100b protein was detectable in the soluble fraction of thyroid tissue. The concentration of S-100b protein in thyroid carcinoma tissue was three to five times higher than in normal thyroid tissue and thyroid adenoma. It is, however, not higher in the thyroid tissue of Graves' disease. The increase of S-100b protein concentration was not remarkable in carcinomatous tissue of the stomach and other digestive organs. The calmodulin content in the thyroid carcinoma tissue increased but the increment was low compared to that of S-100b protein. These data suggest that S-100b protein may play a significant role in cell maturation or differentiation.

Adenoma↗
PubMed1987

Synthesis and beta-lactamase inhibitory properties of 2 beta-[(1,2,3-triazol-1-yl)methyl]-2 alpha-methylpenam-3 alpha-carboxylic acid 1,1-dioxide and related triazolyl derivatives.

Benzhydryl 2 beta-[(1,2,3-triazol-1-yl)methyl]-2 alpha-methylpenam- 3 alpha-carboxylate 1,1-dioxide was prepared by heating benzhydryl 2 beta-(azidomethyl)-2 alpha-methylpenam-3 alpha-carboxylate 1,1-dioxide with (trimethylsilyl)acetylene. The ester group was removed by hydrogenolysis to give sodium 2 beta-[(1,2,3-triazol-1-yl)methyl]-2 alpha-methylpenam-3 alpha-carboxylate 1,1-dioxide (3i, YTR-830), which was found to be a potent inhibitor of various bacterial beta-lactamases. A series of related compounds was prepared in a similar way, and all of these compounds show excellent beta-lactamase inhibitory properties.

Ampicillin↗
PubMed1987

Serum beta-enolase in acute myocardial infarction.

The enzyme beta-enolase (alpha beta and beta beta forms) is present in skeletal and heart muscle and catalyses the glycolysis of 2-phosphoglycerate to phosphoenolpyruvate. The enzyme was measured in serum samples from patients with acute myocardial infarction, angina pectoris, congestive heart failure, and idiopathic cardiomyopathy. Serum concentrations of beta-enolase were significantly increased in acute myocardial infarction but not in the other cardiovascular diseases. Activity peaked approximately 12 to 14 hours after an acute attack of chest pain, and then gradually decreased as the patient recovered. The rise and fall in beta-enolase concentration were faster and steeper than those of creatine kinase activity, particularly in patients in whom activities of both these enzymes were less high. The assay of beta-enolase, which is highly specific and sensitive, has considerable advantages for the early diagnosis of myocardial infarction and the diagnosis of a second episode of myocardial infarction because beta-enolase concentration increases very early and rapidly and clears quickly. These data imply that serum beta-enolase may be a more effective marker for early myocardial infarction, particularly in milder cases, than measurement of creatine kinase activity.

Adult↗
PubMed1986

Congenital goiter sustaining normal level of serum triiodothyronine.

We attempted to elucidate the deficient site of thyroid hormone biosynthesis in the thyroid gland and the mechanism of sustaining normal T3 level in sera of a patient with congenital goiter. TY, a 8-yr-old boy, first noted the onset of a diffuse goiter at the age of 2. There was no clinical evidence of hypothyroidism except for the slight impairment of intellectual development and the awkward physical activity. BMR, T3-RSU and T4 showed low values (-13%, 20.8% and 2.2 micrograms/dl), but serum T3 was normal (180 ng/dl). Serum TSH was 18 microU/ml. The intrathyroidal T3 and T4 were slightly low. Thyroidal 131I uptake was high, but KSCN discharge test was negative. Percent distribution of 131I labelled amino acids in the pancreatin digested thyroid homogenate was 17.4% in MIT, 33.4% in DIT and 11.3% in T3 and T4. Thyroid iodide peroxidase activities in mitochondrial and microsomal fractions were slightly low (19.6 and 26.8 (normal: 32 +/- 3.0 and 37.4 +/- 9.5) mumoles/mg protein). The activity was not increased by the addition of hematin. Thyroglobulin was found to be normal. A biological half life of 131I labelled T4 was shorter (3.5 days) than that of the normal. Electron microscopic examination exhibited the increment and expansion of endoplasmic reticulum in the follicular cell. Low iodide peroxidase activity of this patient may correlate to low T3 and T4 level in the thyroid cell. Moreover, shortened biological half life of T4 implies that normal T3 level in serum is sustained by the accelerated conversion of T4 to T3 in peripheral tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1986

High activity of cyclic 3',5'-nucleotide phosphodiesterase in sera of patient with phaeochromocytoma.

Our previous observations that serum cyclic 3',5'-nucleotide phosphodiesterase activity varied in thyroid disorders and was positively correlated with thyroid function stimulated us to investigate the phosphodiesterase levels in sera of patients with pituitary and adrenal disorders, and the response to glucagon in normal subjects. Both serum cyclic AMP phosphodiesterase (cyclic AMP-PDE) and cyclic GMP phosphodiesterase (cyclic GMP-PDE) activities were measured at a low substrate concentration. Serum cyclic AMP-PDE activity was elevated in five patients with phaeochromocytoma and was not elevated in patients with Cushing's syndrome or acromegaly, compared to the level in normal subjects. Increased enzyme activities returned to normal after resection of the tumours. Intramuscular injection of glucagon to five healthy subjects elevated cyclic AMP levels and cyclic AMP-PDE activity in plasma. These results imply that the increased cyclic AMP level by the activation of cyclase may have induced cyclic AMP-PDE in the target organ and the soluble cyclic AMP-PDE may leak into blood vessels from target organs.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

Effect of somatostatin and dopaminergic agents on bovine pituitary phosphodiesterase activity.

The effects of somatostatin and dopaminergic agents on pituitary cyclic nucleotide phosphodiesterases that had been partially purified through DEAE cellulose column chromatography were studied. Somatostatin, L-dopa, dopamine and CB-154(2-bromo-alpha-ergocriptine) competitively inhibited the pituitary cyclic AMP phosphodiesterase activity, especially that of the low Km enzyme. This inhibition was most potent in the case of somatostatin and CB-154.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

Effect of calmodulin inhibitors on thyroid hormone secretion.

The effect of calmodulin inhibitors, N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) and trifluoperazine, on TSH-induced thyroid hormone secretion from rat thyroid was examined in vivo and in vitro. The ip administration of 5 mg W-7 to the rat inhibited T4 and T3 secretion from rat thyroids at 2, 3, and 4 h after the ip injection of 2 IU TSH, and so did the ip injection of trifluoperazine at 3 and 4 h. However, the ip injection of N-(6-aminohexyl)-1-naphthalene sulfonamide as a control substance did not show any significant inhibition of T4 and T3 release. To identify the site of action of calmodulin, the effect of W-7 on (Bu)2cAMP-induced thyroid hormone secretion was tested in vitro. One hundred micromolar W-7 completely inhibited T4 release from the rat thyroid when it was enhanced by TSH or (Bu)2cAMP, suggesting that the inhibitory effect of W-7 is subsequent to cAMP formation. These results suggest that calmodulin may play a role in thyroid hormone secretion from the thyroid, acting beyond cAMP formation.

Animals↗
PubMed1986

Enolase subunits in patients with neuroendocrine tumors.

Concentrations of the alpha-, beta-, and gamma-subunits of enolase in surgically resected tumors and serum obtained from patients with various endocrine tumors were measured by a sensitive enzyme immunoassay system. Tissue concentrations of the gamma-subunit were significantly elevated in patients with neuroendocrine tumors concurrent with high concentrations of the gamma-subunit in their serum, which fell to normal in 90% of those who underwent tumor resection. Immunohistochemical analysis revealed that considerable amounts of the gamma-subunit were contained specifically in these tumors. These results indicate that the gamma-subunit of enolase is a useful marker for diagnosing and monitoring patients with neuroendocrine tumors.

Adult↗
PubMed1985

Gigantism associated with McCune-Albright's syndrome.

The case of a 16 year-old boy with McCune-Albright's syndrome which is rarely accompanied by gigantism was studied endocrinologically. The stimulation of growth hormone (GH) release by hypoglycemia, the decline of elevated GH by hyperglycemia and a little lower somatostatin like immunoreactivity (SLI) may support abnormalities of hypothalamic function, but the existence of pituitary microadenoma cannot be ruled out because of the paradoxical suppression of GH release by oral administration of bromocriptine (CB-154) and L-DOPA and the stimulation of GH release by intravenous administration of TRH.

Adolescent↗
PubMed1985

Effect of hypophysectomy on cyclic 3',5'-nucleotidemetabolizing enzymes in the rat thyroid gland.

Adenylate cyclase and cyclic AMP phosphodiesterase activities in the thyroid gland were significantly reduced after hypophysectomy, followed by a gradual restoration of the enzyme activities to the levels seen in sham-operated rats whereas a slight and persistent reduction was evident in guanylate cyclase and cyclic GMP phosphodiesterase activities in the same tissue. These changes in enzyme activities were restored by TSH administration but not by ACTH. The recovery of activity produced by TSH administration was inhibited by cycloheximide. Hypophysectomy, or TSH and cycloheximide administration, did not produce any significant changes in the concentrations of calmodulin, suggesting that the alteration of these enzyme activities is not induced by a decrease in the concentration of calmodulin. Since forskolin activation of adenylate cyclase did not restore the reduced activity in the hypophysectomized rat thyroid to the level found in the sham-operated control rat thyroid, we conclude that there is a reduction of the amount of enzyme after hypophysectomy rather than a change of the active site on adenylate cyclase. The spontaneous restoration of adenylate cyclase and cyclic AMP phosphodiesterase activities after hypophysectomy implies that cyclic AMP-metabolizing enzymes are responsive to an autoregulatory mechanism in thyroid follicular cells.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1985

Serum cyclic 3',5'-nucleotide phosphodiesterase activity in myocardial infarction.

The activities of cyclic 3',5'-nucleotide phosphodiesterases which hydrolyze cyclic 3',5'-nucleotides were measured in sera from patients with an acute myocardial infarction, angina pectoris and other heart diseases. Cyclic AMP and cyclic GMP phosphodiesterase activities were significantly elevated in acute myocardial infarction, but not in angina pectoris and other cardiovascular diseases. The peak activity appeared approximately within 24 hours following the acute attack of chest pain, and then gradually decreased as the patient recovered. The observed changes of cyclic 3',5'-nucleotide phosphodiesterase activity were similar to that of the other enzyme activities such as GOT, CPK and LDH in sera of acute myocardial infarction. These data reflect damage of myocardial cells during myocardial infarction.

3',5'-Cyclic-AMP Phosphodiesterases↗