Search PubMed⌕ Search

Biomedical subjects

H Seo

Publications and source records attributed to H Seo.

At least 181 records · Page 10Linked to original sources

[Cloning of human thyroxine-binding globulin cDNA, isolation of the gene, and its transcriptional regulation].

Cloning of human thyroxine-binding globulin (TBG) cDNA and gene revealed that the primary structure of TBG and its gene organization are homologous to those of serine protease inhibitors (serpin). The transfection study of the TBG promoter linked to chloramphenicol acetyltransferase gene demonstrated that the putative hepatocyte nuclear factor-1 site (located at -77 approximately -65) is required for the transcription of the TBG gene. In addition, the sequence located at -218 approximately -102 is responsible for liver-specific expression of the gene. Estrogen, thyroid hormone and glucocorticoid had little effect on the promoter activity, suggesting that the alteration of serum TBG concentration by these hormones is due to their effect on posttranslational steps in TBG synthesis and secretion.

Animals↗

[Experimental studies on Nicaraven as radioprotector--free radical scavenging effect and the inhibition of the cellular injury].

In the present study, firstly the antioxidant effect of Nicaraven was observed by examining the direct free radical scavenging effect with ESR. Dose dependent effects were shown in scavenging both of superoxide and hydroxyl radicals. In the study to check whether Nicaraven inhibits hydroxyl radical formation or degrades the spin adduct of DMPO with hydroxyl radical, the effect of Nicaraven was suggested that it inhibited hydroxyl radical formation itself. Secondly, it was recognized fluorophotometrically that the inhibiting effect of the agent on the superoxide and hydroxyl radicals promoted damage to benzoate, deoxyribose and some amino acids. The inhibiting effect was nearly the same as that of mannitol. Furthermore, the inhibition of the cellular injury induced by ferrous sulphate was investigated in NIH3T3 cells. The addition of Nicaraven to the cells after 6 hours of reaction with FeSO4, the inhibition of the cellular injury was significant (p < or = 0.01). The effect of Nicaraven was recognized as a radioprotector in vitro. The agent suggested to be able to produce recovery from the damage induced by irradiation at the cellular level.

3T3 Cells↗

The POU-domain protein Oct-1 is widely expressed in adult rat organs.

The cDNA encoding a rat Oct-1 POU-domain was cloned by the reverse transcription-polymerase chain reaction method and subsequently Oct-1 mRNA expression was investigated. Our results show that the POU-domain of Oct-1 has been highly conserved during vertebrate evolution and that Oct-1 mRNA is widely expressed in various organs of adult rat.

Actins↗

Factors related to the recurrent hyperfunction of autografts after total parathyroidectomy in patients with severe secondary hyperparathyroidism.

Total parathyroidectomy with autotransplantation has been widely accepted as the appropriate treatment for patients with hyperparathyroidism due to chronic renal failure on long term hemodialysis. However, recurrence has been an enigma and therefore, the factors involved in the recurrence of hyperparathyroidism were studied in 128 patients followed for more than 2 years after surgical treatment. The preoperative serum parathyroid hormone (PTH) concentrations correlated with the total weights of the parathyroid glands. When the original autotransplanted glands were divided into two groups, being diffuse and nodular, the rate of recurrent hyperparathyroidism due to graft hyperfunction was significantly higher in the patients who received nodular glands (24%) than in those who received diffuse glands (8.4%) (P < 0.05). To investigate whether PTH synthetic activity is different in diffuse and nodular glands, the amount of PTH mRNA was studied by in situ hybridization. There was no significant difference in the amount of PTH mRNA in the cells from either diffuse or nodular glands. These data suggest that the recurrence of hyperparathyroidism is not due to enhanced PTH synthetic activity of autotransplant grafts but to the abnormal growth rate of the transplanted gland.

Adult↗

Effect of thyroid hormone on epidermal growth factor gene expression in mouse submandibular gland.

Epidermal growth factor (EGF) in mouse submandibular gland (SMG) is synthesized in the granular convoluted tubular (GCT) cells. The synthesis of EGF in SMG has been shown to be increased by thyroid hormone. This increase was attributed to the increase in EGF mRNA. Not known is how thyroid hormone increases the mRNA level. In the present study the effect of thyroid hormone administration on EGF gene expression in SMG was studied in hypothyroid mice. Hypothyroidism was induced by treating the mice with propylthiouracil. The amount of SMG EGF mRNA was markedly decreased in hypothyroid mice. Administration of T3 increased the mRNA in a dose-dependent manner. The increase in EGF mRNA by T3 was evident as early as 6 h after T3 administration. A nuclear run-off assay indicated that the induction of EGF gene expression by T3 is at a transcriptional level. Bromodeoxyuridine incorporation into GCT cells was not affected by T3 administration, suggesting that T3 does not cause the proliferation of these cells. In situ hybridization revealed that T3 increases EGF mRNA in GCT cells at a single cell level. These results suggest that thyroid hormone increases EGF gene transcription without affecting cellular proliferation.

Animals↗

Effects of thyroid and glucocorticoid hormones on the level of messenger ribonucleic acid for iodothyronine type I 5'-deiodinase in rat primary hepatocyte cultures grown as spheroids.

The activity of type I 5'-deiodinase (5'DI) is known to correlate with thyroid status; it is high in hyperthyroidism and low in hypothyroidism. Recently, it was shown that the increased activity of type I 5'DI in hyperthyroidism is associated with an increase in enzyme contents as well as its mRNA in liver. However, it remains unknown whether thyroid hormone directly regulates the expression of 5'DI mRNA in hepatocytes. In this study, the direct actions of thyroid hormone as well as rT3 and dexamethasone on type I 5'DI mRNA were investigated using primary cultures of rat hepatocytes. Hepatocytes were prepared from euthyroid rats by collagenase perfusion and plated either on collagen-coated dishes for conventional monolayer cultures or on positively charged dishes for spheroid cultures. After hormonal treatments, the levels of mRNAs for type I 5'DI and albumin were determined by Northern blotting. In spheroid cultures, T3 increased type I 5'DI mRNA in a dose- and time-dependent manner, whereas the albumin mRNA level was not altered. A lesser effect was observed in hepatocytes cultured as monolayers. The T3-induced increase in 5'DI mRNA was not inhibited by pretreatment with cycloheximide, indicating that the effect of thyroid hormone on 5'DI mRNA is direct, not requiring de novo protein synthesis. rT3 did not affect the levels in type I 5'DI mRNA increased by T3. On the other hand, dexamethasone alone increased 5'DI mRNA and, when added together with T3, had a synergistic effect. In contrast to T3, dexamethasone increased albumin mRNA. Dexamethasone-induced increases in mRNAs for 5'DI and albumin were inhibited by pretreatment of cycloheximide. The present study indicated that T3 increases 5'DI mRNA through a direct action on its gene, whereas the effect of dexamethasone requires de novo synthesis of a protein factor(s).

Animals↗

The relative expression of mutant and normal thyroid hormone receptor genes in patients with generalized resistance to thyroid hormone determined by estimation of their specific messenger ribonucleic acid products.

Generalized resistance to thyroid hormone (GRTH), is a syndrome of reduced tissue responsiveness to thyroid hormone. So far, mutations linked to GRTH have been only detected in the hormone-binding domain of the human thyroid hormone receptor (hTR)-beta gene. Although there is no doubt that these mutations result in abnormal hTRs, there is a conspicuous lack of correlation between the severity of clinical manifestations and the degree of functional impairment of the mutant hTRs. In this work we examined whether variable expression of mutant genes relative to the normal genes could explain the observed discrepancies. The relative amounts of mutant and normal hTR beta and normal hTR alpha messenger RNAs in fibroblasts from normal subjects and those from individuals with GRTH were estimated by coamplification of their complementary DNA products. Heterozygous subjects with GRTH from two families manifesting differences in the severity of clinical manifestations expressed equally both normal and mutant hTR beta alleles. Furthermore, there was no compensatory increase in the expression of the normal hTR alpha gene in these individuals nor in fibroblasts from members of a third family with homozygous deletion of the hTR beta gene. In vitro treatment with thyroid hormone did not affect the results. It is concluded that the apparent discrepancies between the functional impairment of the mutant hTRs and the clinical manifestations of GRTH are not due to quantitative differences in the expression of the normal or mutant hTR genes but more likely to variations in the interactions of the mutant hTRs with the normal hTR beta, hTR alpha and nuclear stabilization factors.

Alleles↗

Human thyroxine-binding globulin gene: complete sequence and transcriptional regulation.

T4-binding globulin (TBG) is a glycoprotein of hepatic origin which transports thyroid hormone in serum. To characterize the human TBG (hTBG) gene, we studied its genomic organization, promoter activity, and regulation. To this purpose, we isolated from liver a complete hTBG cDNA clone containing the 5'-untranslated region and localized the transcription start site (TSS). The analysis of genomic clones revealed that the hTBG gene consists of five exons and that its exon-intron organization is similar to that of other members of the serine protease inhibitor family. The first exon (exon 0) is a short noncoding sequence located 1.62 kilobase pairs (kbp) upstream from exon 1. Potential cis-acting transcriptional regulatory elements including a TATA box, a CAAT box, and a hepatocyte nuclear factor-1 binding motif were identified in the upstream region. A reporter gene in which 3.2 kbp of the 5'-flanking region, including exon 0, was inserted upstream of the bacterial chloramphenicol acetyltransferase gene showed significant activity when transfected into a hepatblastoma-derived (HepG2) cell line. The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, down-regulated the promoter activity by more than 80% and completely inhibited hTBG synthesis, whereas thyroid hormone, glucocorticoid, estrogen, and nicotinic acid had little, if any, effect. A series of 5'-deletions revealed that the fragment -218 to +4 from the TSS had the highest promoter activity, nearly 1000-fold greater than the promoterless chloramphenicol acetyltransferase construct. When nonhepatocyte-derived cell lines (CV-1 and CHO) were tested, promoter activity was reduced by a factor of 100, showing that the promoter works in liver-specific manner. The region -218 to -102 contains liver-specific enhancer elements, since deletion to nucleotide -101 resulted in a profound reduction of the promoter activity in HepG2 cells but not in CV-1 or CHO cells. On the other hand, mutational disruption of the putative hepatocyte nuclear factor-1 site (located 65 bp upstream of the TSS) completely abolished the promoter activity in all cell lines, indicating that this site is absolutely required for the transcription of the hTBG gene.

Amino Acid Sequence↗

Sequence of a variant thyroxine-binding globulin (TBG) in a family with partial TBG deficiency in Japanese (TBG-PDJ).

Thyroxine-binding globulin (TBG) is the major transport protein of thyroid hormones in human serum. In this communication, we present a sequence abnormality of the TBG-gene in a Japanese family manifesting partial TBG deficiency (TBG-PDJ). The propositus was a male with a reduced concentration of TBG (3.2 micrograms/ml). Thyroid function tests suggested that the inheritance of this TBG abnormality was X-linked. The TBG exhibited increased heat-lability compared with the common type TBG (TBG-C). The isoelectric focusing pattern of this TBG molecule was indistinguishable from TBG-C. Genomic DNAs from white blood cells of four members of a TBG-PDJ family were subjected to polymerase chain reaction (PCR), and the products were sequenced. The sequencing of the entire coding exons and exon/intron junctions of TBG allele of the propositus revealed a single nucleotide substitution: CCT (proline) to CTT (leucine) at amino acid 363 of the TBG-C. The heterozygosity as revealed by the direct sequencing of the PCR product correlated with the TBG concentration in serum. The proline to leucine substitution may cause a change in the TBG tertiary structure and result in decreased heat stability, resulting in decreased TBG levels in the affected subjects.

Base Sequence↗

Gene screening of 23 Japanese families with complete thyroxine-binding globulin deficiency: identification of a nucleotide deletion at codon 352 as a common cause.

Thyroxine-binding globulin (TBG) is a major thyroid hormone transport protein in human serum. Its complete deficiency (TBG-CD) is one of inherited TBG abnormalities that transmit on X-chromosome. We previously reported a nucleotide deletion at codon 352 of the TBG gene (TBG-CDJ) in Japanese families with TBG-CD. To determine the prevalence of this mutation in Japanese with TBG-CD, 23 affected subjects (19 males and 4 females) belonging to unrelated families living in 4 major islands of Japan were analyzed with regard to the mutation at codon 352. Their genomic DNAs were amplified by the polymerase chain reaction with allele specific primers. Nineteen male and four female subjects were shown to have the mutation as hemizygotes and heterozygotes, respectively. It is concluded that TBG-CDJ may be a common cause of TBG-CD in Japanese and might have appeared in the ancestors of the Japanese after the human race divergence.

Alleles↗

Creatine kinase-MB protein mass is a better indicator for the assessment of acute myocardial infarction in the lower range of creatine kinase level.

The theoretical and clinical validity of immunochemiluminometric assay of creatine kinase (CK)-MB protein mass was assessed in patients with acute myocardial infarction and the results were compared with those of immunoinhibition assay of CK activity. Serial changes of both CK-MB protein mass and CK-MB activity were analyzed in 20 consecutive patients. In all 312 samples from 20 patients, protein mass and activity of CK-MB showed good correlation. The exponential fitting of the time-value curve of CK-MB protein mass showed a better correlation coefficient than that of CK-MB activity (0.97 +/- 0.02 vs 0.93 +/- 0.07, p < 0.05), indicating that the CK-MB level measured by the immunochemiluminometric assay was less scattered than that measured by the immunoinhibition method. This finding was most evident at lower CK-MB values (< 500 IU/l). The rate of disappearance from serum of CK-MB protein mass was faster than that of CK-MB activity (0.54 +/- 0.23 hr-1 vs 0.28 +/- 0.13 hr-1, p < 0.001). This may indicate that some amount of the CK-MB activity may be inactivated in the early phase of the release into the serum from the necrotic myocardium. Thus, the immunochemiluminometric assay of CK-MB protein mass has superiority in the diagnosis of acute myocardial infarction compared with the immunoinhibition method, especially when the measured CK-MB level is low. This feature may be useful to distinguish a small myocardial infarction from severe ischemia without myocardial necrosis.

Aged↗

Hormonal responses to head-out water immersion diminish after exposure to head-down tilt.

It has been postulated that gravitational change from 1 g to microgravity may cause cephalad fluid shift, resulting in suppression of antidiuretic hormone (ADH) secretion and diuresis (Gauer-Henry's reflex). However, results obtained in space flights did not confirm this. Since astronauts are confined at supine position for hours before launch, this posture may abolish the reflex in space flight. To investigate this possibility, effects of head-out water immersion (WI) after 2-hour head-down tilt (HDT) on hormonal and metabolic responses were examined and compared with those after 1-hour upright posture (UP). Hematocrit decreased by WI after UP, indicating hemodilution, but it did not change by WI after HDT. Plasma ADH, renin activity and aldosterone fell and atrial natriuretic peptide (ANP) rose by WI after UP, resulting in increased urine flow. On the other hand, appreciable hormonal changes were not elicited by WI after HDT, and urine flow stayed unchanged. These results indicate that fluid shift and hormonal and metabolic responses to WI are strongly attenuated by the prior exposure to HDT. Pre-launch posture of astronauts may at least partly explain why either suppression of ADH or diuresis was not observed on arrival at space.

Adult↗

De-acclimatization process of rats acclimatized to high altitude hypoxia.

The de-acclimatization process in rats acclimatized to high altitude hypoxia was analyzed according to the changes in the activities of hepatic enzymes. The activities of tryptophan 2,3-dioxygenase and tyrosine aminotransferase in the liver of non-acclimatized rats were increased, whereas those of acclimatized rats were decreased after exposure to a simulated altitude of 8,000 m. When the acclimatized rats were kept under normoxic conditions for 8 days and over, the suppression of enzyme induction was nullified, and both enzymes were induced by exposure to the simulated 8,000 m altitude. De-acclimatization of rats acclimatized to hypoxia can be completed in 8-11 days.

Acclimatization↗

Urinary excretion of stress hormones of rats in tail-suspension.

Tail-suspension of rats has been employed for the study of disuse atrophy of hindlimb muscles and bones. From our study, it is suggested that stress exacerbates muscle and bone atrophy; however, the determination of stress hormones has been inappropriately performed. For assessing the effect of tail suspension on stress hormone secretion, suspension was performed for 7 days in a metabolic cage. Urinary excretions of corticosterone, catecholamines and antidiuretic hormone were determined during the 7-day suspension. Urine volume was unchanged during the suspension period, whereas water consumption was decreased during suspension. Urinary excretion of corticosterone and catecholamines increased significantly during the initial 3 days of suspension. The excretion of antidiuretic hormone increased throughout the suspension period. Our results demonstrated that the determination of urinary excretion of these hormones is useful for evaluating the stress reaction.

Adrenal Glands↗

[Noninvasive identification of left main and triple vessel coronary artery disease using dipyridamole thallium scintigraphy].

The diagnostic value of dipyridamole thallium scintigraphy for the noninvasive identification of left main (LM) and triple vessel (TV) coronary artery disease (CAD) was evaluated in 615 consecutive patients with known or suspected CAD. One hundred thirty-nine patients had LM or TVCAD; the remaining 476 patients had limited CAD (double vessel CAD in 112, single vessel CAD in 235, insignificant lesions in 129). Patients with LM or TVCAD, compared to those with limited CAD, had a higher incidence of diffuse slow washout (58 vs 20%, p < 0.0001), extensive fixed defects (21 vs 6%, p < 0.0001) and extensive reversible defects (32 vs 8%, p < 0.0001). During dipyridamole loading, the incidence of chest pain was higher (65 vs 41%, p < 0.0001), and the magnitude of ST depression was greater (0.16 +/- 0.14 vs 0.04 +/- 0.07 mV, p < 0.001) in patients with LM or TVCAD than in those with limited CAD. Stepwise discriminant analysis using scintigraphic imaging achieved a sensitivity of 69%, a specificity of 79%, and an accuracy of 77% for diagnosing patients with LM or TVCAD. After including clinical markers of ischemia during dipyridamole loading, multivariate analysis revealed an improved diagnosis with a sensitivity of 71%, a specificity of 85%, and an accuracy of 82%. These results clearly show the usefulness of scintigraphic imaging as well as the significance of careful assessment of clinical markers of ischemia during dipyridamole loading for the noninvasive identification of LM and TVCAD.

Adult↗

[Sequential changes in SPECT using 201T1 chloride during the treatment of intracranial gliomas].

The authors followed up the change in SPECT using 201Tl chloride (Tl-SPECT) according to the course of treatment of intracranial gliomas and analyzed the difference in Tl-SPECT between the stable and progressive groups. The subjects were 26 series of supratentorial gliomas subjected to Tl-SPECT before and after the treatment (radio-therapy and chemotherapy). They were put on Tl-SPECT after 10 minutes (early image) and 4 hours (delayed) following 74 MBq of 201Tl chloride intravenous injection. Besides, RI count ratio (L/N) in the tumor lesion (L) and contralateral parenchyma (N) was measured. The patients were divided into stable and progressive groups judging from the therapeutic effects, the change in L/N ratio between before and after the treatment was analyzed. The stable group showed a significant post-treatment decrease in L/N ratio compared with a significant post-treatment increase therein for the progressive group. This result suggested Tl-SPECT to change according to the course of treatment and to be applicable to the judgement of the therapeutic effect on gliomas.

Adolescent↗

Collagen and alkaline phosphatase gene expression during bone morphogenetic protein (BMP)-induced cartilage and bone differentiation.

Endochondral bone formation induced by bone morphogenetic protein (BMP) involves expression of collagen Types I and II and alkaline phosphatase (ALP) genes. Expression of these genes was studied in mice after implantation of BMP. The amount of Type I collagen mRNA increased from Day 3 to Day 7, when mesenchymal cell aggregation was observed. On Day 17, Type I collagen mRNA expression was correlated with an increased number of osteoblasts. Type II collagen mRNA increased from Day 7 and coincided with chondroblast appearance. This increase was suppressed by Day 17, although hypertrophic and degenerative chondrocytes were present. Alkaline phosphatase mRNA increased markedly from Day 7 with the appearance of chondroblasts. The high level of ALP mRNA continued until Day 11, during chondrogenesis. Mineral deposition was first observed roentgenographically on Day 11. Thus, BMP-induced bone formation occurs with the expression of collagen Types I and II and ALP genes.

Alkaline Phosphatase↗