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Biomedical subjects

K Miyai

Publications and source records attributed to K Miyai.

At least 109 records · Page 6Linked to original sources
PubMed1990

The distinct roles of alpha- and beta-subunits of human thyrotropin in the receptor-binding and postreceptor events.

The roles of alpha- and beta-subunits of human TSH (hTSH) were studied by investigating the inhibitory effects of monoclonal antibodies on the biological activity of hTSH. Four monoclonal antibodies directed toward different epitopes on the beta-subunit (hTSH beta) inhibited completely the receptor binding of hTSH to FRTL-5 rat thyroid cells. In contrast, five monoclonal antibodies directed toward different epitopes on the alpha-subunit had little or no effect on the receptor binding. Furthermore, four of five alpha-subunit-specific antibodies and three of four hTSH-specific antibodies inhibited both hTSH-induced cAMP accumulation and thymidine uptake in FRTL-5 cells, in a dose-response manner. One hTSH (alpha-beta heterodimer)-specific antibody which did not recognize the free subunits also had the inhibitory effect on both the receptor binding and hTSH-induced cAMP accumulation. These results strongly suggest that hTSH beta is indispensable for recognizing the receptors on FRTL-5 cells and that the alpha-subunit is required for signal transduction in postreceptor step(s). In addition, it is also suggested that the highly conformational structure of hTSH is absolutely essential for the biological activity.

Animals↗
PubMed1990

Deoxyribonucleic acid analyses of five families with familial inherited thyroid stimulating hormone deficiency.

Five families with familial inherited TSH deficiency, reported to date, were examined for the TSH beta gene at the nucleotide level. The first family carries a single base substitution in the 29th codon which lies in the so-called CAGYC region; GCA (glycine) is replaced by AGA (arginine). This substitution induces conformational changes of the beta-polypeptide which make it unable to associate with the alpha-subunit. This mutation generates a new cleavage site for a restriction endonuclease MaeI, a new marker that can be used for DNA diagnosis. The second and third families were found to carry the same nucleotide substitution. Also, all three families were associated with an additional single base substitution in intron 2 as a polymorphic change, suggesting that these three families may have originated from the same single founder from Shikoku Island in Japan. The nucleotide sequence from the fourth and fifth families showed no alterations in the TSH beta gene from the about -200 basepair up-stream region to the polyadenylation site.

Amino Acid Sequence↗
PubMed1990

Low prevalence of thyrotropin receptor antibody in primary hypothyroidism in Japan.

The prevalence of TSH receptor antibody (TRAb), measured by RRA assay (TSH-binding inhibitor immunoglobulin, TBII) and biological stimulation-blocking assay (thyroid-stimulation blocking antibody, TSBAb), was examined in 134 consecutive patients with primary hypothyroidism due to autoimmune thyroiditis [83 patients with goitrous Hashimoto's disease (group A) and 51 with primary atrophic hypothyroidism (group B)]. In group A, TBII was detected in 6 patients (7%), TSBAb in 7 (8%), and both in 4 (5%). Similarly, in group B, TBII was detected in 7 patients (14%), TSBAb in 7 (14%), and both in 5 (10%). TBII with TSBAb activity was low or moderate in group A, but strongly positive in group B. No relationship was apparent in either group between TBII or TSBAb activity and any clinical or laboratory parameter examined. Moreover, no clinical or laboratory findings distinguished patients with TRAb from those without. The low prevalence of TRAb in primary hypothyroidism suggests that intrathyroidal cell-mediated destructive mechanisms may be more important in the pathogenesis of hypothyroidism in autoimmune thyroiditis.

Adult↗
PubMed1990

Site-specific mutagenesis of human chorionic gonadotrophin (hCG)-beta subunit: influence of mutation on hCG production.

The heterodimeric glycoprotein hormones, human chorionic gonadotrophin (hCG), LH, TSH and FSH, consist of two non-covalently linked subunits, the alpha and beta subunits. The beta subunit is specific for each hormone and is responsible for the biological specificity, but the beta subunits of different hormones show some degree of structural homology. The CAGY (cysteine-alanine-glycine-tyrosine) region is one of the amino acid sequences that is homologous in different beta subunits and is highly conserved between species. In the present study, site-specific in-vitro mutagenesis was used to change three individual nucleotides in the centre of the CAGY region of the hCG-beta subunit, and the effects of these mutations on hCG production was determined by in-vitro transcription and then translation in Xenopus laevis oocytes. The results indicate that the CAGY region, particularly the glycine residue at position 36 in the beta subunit, is essential for the production of hCG. This finding is consistent with previous studies showing that this region is necessary for the biological activity of human TSH.

Amino Acid Sequence↗
PubMed1990

Massage therapy on neck: a contributing factor for destructive thyrotoxicosis?

A 57-year-old woman with Hashimoto's disease is described who developed transient destructive thyrotoxicosis subsequently after she underwent physical massage therapy over her shoulder to neck, together with the goiter, for muscle stiffness in that part. This case supports the concept that physical vigorous manipulation might be a contributing factor for thyrotoxicosis in cases predisposed with autoimmune thyroiditis.

Autoantibodies↗
PubMed1990

Physiologic thyroid activation in normal early pregnancy is induced by circulating hCG.

In normal early pregnancy, serum free thyroxine (T4) increases and serum TSH decreases, indicating that the thyroid gland is activated physiologically. To identify the factor responsible for this thyroid activation, we measured the serum thyroid-stimulating activity in comparison with the serum level of hCG in 39 normal women in early pregnancy. Serum thyroid-stimulating activity was measured by a sensitive cyclic adenosine 3',5'-monophosphate (cAMP) accumulation assay using a rat thyroid cell line (FRTL-5). Thyroid-stimulating activity was detected in 37 women (95%), and the activities of individuals correlated positively with their serum free T4 levels (r = 0.474; P less than .01) and negatively with their serum TSH levels (r = -0.376; P less than .02). Moreover, serum thyroid-stimulating activity correlated closely with the serum hCG level (r = 0.741; P less than .001), but was completely abolished by pre-treatment of the sera with hCG antibodies. These data indicate that in normal early pregnancy, the thyroid gland is physiologically activated by serum hCG, which has intrinsic thyroid-stimulating activity.

Animals↗
PubMed1990

[Development of ELISPOT assay for thyroid autoantibody-producing cells].

A new assay system for detection of thyroid-autoantibody-producing cells was developed. This assay is based on the ELISPOT method with antigen-coated nitrocellulose membranes in 96-well microfilter plates. This was more sensitive than conventional methods such as a radioimmunoassay and a passive agglutination method for detection of thyroid-autoantibody production. The coefficients of inter- and intra-assay variations for antibody-producing cells were less than 6.5%. Thus, this assay system can be used to analyse the thyroid-specific immunological abnormalities as a routine test.

Agglutination Tests↗
PubMed1990

Alkaline phosphatase activity in hepatic tissue and serum correlates with amount and type of bile acid load.

Bile acids stimulate synthesis of alkaline phosphatase (ALPase) in the liver. We studied how alterations in bile acid type and load affect ATPase activity in hepatic tissue and in the serum. We increased the load of natural bile acids in rats by bile duct obstruction (BDO) or by creating a shunt between the common bile duct and superior vena cava (choledocho-caval shunt or CCS). Concentration of bile acids and ALPase activity in hepatic tissue rose more rapidly in the BDO model than in CCS. ALPase activity on the hepatocellular surface, normally confined to the canaliculus, spread outward to involve basolateral membrane in livers with high total hepatic ALPase activity. When the bile acid pool was reduced by a 12-hour biliary drainage in the CCS model, surface distribution of ALPase reverted to a nearly normal pattern. We substituted the endogenous bile acid pool with an equimolar amount of the single bile acid, taurocholic (TCA), tauroursocholic, taurohyocholic, or tauroursodeoxycholic acid in the CCS. The first two bile acids have a 12 alpha-hydroxyl group, whereas the latter two do not. After 12 hours, hepatic ALPase activity was increased with TCA or tauroursocholic substitution, but not with taurohyocholic or tauroursodeoxycholic. Again, surface distribution of ALPase activity correlated with the tissue ALPase activity. However, the serum activity increased significantly only with TCA, the most detergent of the bile acids. In bile fistula rats only infusion of TCA accelerated biliary secretion of ALPase. The above results suggest that hepatic synthesis and serum activity of ALPase are influenced by two different features of bile acids: the former by structure (the 12 alpha-hydroxyl group) and the latter by a physical property (detergency).

Alkaline Phosphatase↗
PubMed1990

[Correlation between intracellular alkaline phosphatase activities and incidence of toxic granules in neutrophilia].

We examined the intracellular alkaline phosphatase (NIAP) activities in peripheral neutrophils in 15 healthy subjects and 15 patients with inflammatory diseases, and compared them with the percentages of neutrophils with cytoplasmic toxic granules (NTG), which is thought to be induced by infection. NIAP activities were markedly increased in patients and significantly correlated with the percentages of NTG. These data indicate that measurement of NIAP activity is useful for the diagnosis of infections and/or inflammatory diseases.

Alkaline Phosphatase↗
PubMed1990

[Intracellular alkaline phosphatase activities in myelodysplastic syndrome].

We examined the intracellular alkaline phosphatase (NIAP) activities in peripheral neutrophils in 15 normal controls, 4 patients with myelodysplastic syndrome, and 4 with chronic myeloid leukemia. NIAP activities were decreased in myelodysplastic syndrome in comparing to normal controls (p less than 0.01). These data suggest that measurement of NIAP activity is useful for supporting a diagnosis of myelodysplastic syndrome.

Alkaline Phosphatase↗
PubMed1990

Thyroxine requirement during pregnancy for replacement therapy of hypothyroidism.

We examined the dose requirements of thyroxine (T4) and desiccated thyroid during eight pregnancies of six women who had undergone total thyroidectomy for thyroid carcinoma. In five pregnancies from four patients treated with T4, serum free T4, which was measured by a newly developed radioimmunoassay, decreased during pregnancy but increased above the normal range after delivery. Consistent with these changes in free T4, serum TSH (measured by a highly sensitive immunoradiometric assay) increased during pregnancy but returned to an undetectable level after delivery, with one exception. The serum triiodothyronine (T3)-to-T4 ratio, which is related to peripheral conversion of T4 to T3, was lower in patients treated with T4 than in normal controls, regardless of pregnancy. The ratio decreased further during pregnancy, and so relative deficiency of T3 during pregnancy was suspected, especially in T4-treated patients. On the other hand, in two pregnancies from two other patients treated with desiccated thyroid at a dose most equivalent to that of T4, serum free T4 decreased to a low-normal value during gestation but returned to the normal range after delivery, whereas serum TSH scarcely changed during pregnancy. These findings indicate that replacement therapy for pregnant patients with hypothyroidism after total thyroidectomy should include an increased dose of T4; in contrast, the dose of desiccated thyroid need not be changed.

Female↗
PubMed1990

[Detection of asymptomatic prolactinoma by a mass screening program].

Mass screening for prolactinoma was performed among the general population of 10,550 normal adults (8,450 men and 2,100 women) using a paired assay method for serum PRL. Forty subjects with hyperprolactinemia were studied. There were five patients with pituitary prolactinoma, and 10 with 'big' prolactinemia. The patients with prolactinoma had few if any complaints. The occurrence of asymptomatic big prolactinemia showed marked female predominance. The implication of such a screening program for laboratory medicine in future is two-fold: 1) prospect of laboratory 'physician' taking active role in the promotion of mass screening program to cover wide range of disorders affecting adult population and 2) feasibility of analyzing or discovering subclinical disorders of academic interest, being allowed to explore every single individual in the population.

Adult↗
PubMed1989

[Eel calcitonin treatment on patients with urogenital carcinoma for relief of pain from metastatic bone lesions].

Forty-seven patients of advanced urogenital carcinoma with bone metastasis were treated with eel calcitonin (CT) to relieve severe pain from metastatic bone lesions. Patients were 45 males and 2 females with a mean age of 72.9. CT was administered intravenously at a daily dose of 160 units for 10 days. The efficacy of CT on relief of pain was estimated using a mark sheets filled by each patient and his or her doctor. And also the amount of analgesics given to patients before and after the administration of CT were checked. CT was effective on 77% of patients to reduce severe bone pain, especially on osteoblastic lesions metastasized from prostatic carcinoma. CT administration decreased the amount of analgesics in 37% of the cases. As toxicity, nausea and vomiting which stopped the CT administration were observed in only one From these results, we conclude that CT is quite useful drug for relief of severe bone pain from metastatic lesions in patients with urogenital carcinoma.

Aged↗
PubMed1989

[Enzyme immunoassay of 17-hydroxyprogesterone in dried blood spot on filter paper using specific antibody for 17-hydroxyprogesterone].

Specific antiserum for 17-hydroxyprogesterone (17-OH-P) was prepared by immunizing 7 alpha-(2-carboxyethylthio)-17-OH-P conjugated bovine serum albumin (BSA) in rabbits. Using this antiserum, 17-OH-P enzyme immunoassay for dried blood spots on filter paper was established. As a label, alkaline phosphatase was coupled covalently with 7 alpha-carboxy-methylthio-17-OH-P by carbodiimide method. B/F separation was carried out by the addition of anti-rabbit IgG goat antiserum. All specimens used were punched out with a paper puncher of 3mm diameter. The assay sensitivity was 2pg/tube, which was estimated by two standard deviation at zero concentrations of the calibration curve. Cross reactivities of this antibody were as follows: 11-deoxycortisol (8.21%), 17-OH-pregnenolone (3.33%), progesterone (1.67%), 11-deoxycorticosterone (0.31%), cortisol (0.16%), pregnenolone-3-sulfate Na salt (0.03%), dehydroepiandrosterone (DHEA) (less than 0.03%), 16 alpha-OH-DHEA (less than 0.03%), DHEA-3-glucuronide (less than 0.03%), DHEA-3-sulfate Na salt (less than 0.03%), pregnenolone (less than 0.02%). Intra- and inter-assay coefficient of variations were 4-14% and 9-18%, respectively. In normal babies, 17-OH-P concentrations measured directly (without sample extraction) were below 23pg/disk (n=204). The histogram of 17-OH-P level in normal babies obtained by the direct method was distributed lower than that obtained by the enzyme immunoassay system (range: 4-79pg/disk, n=268) which used antibody raised against 17-OH-P-3-O-carboxymethyloxime conjugated BSA (Enzaplate, Sapporo Diagnostic Laboratory).(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗