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Biomedical subjects

H Seo

Publications and source records attributed to H Seo.

At least 91 records · Page 5Linked to original sources
PubMed1998

Changes in urinary excretion of deoxypyridinoline in tail-suspended rats: effects of a bisphosphonate, YH529.

Urinary excretion of deoxypyridinoline (D-Pyr) has been shown to be a useful marker for bone resorption. In this study, we investigated whether D-Pyr could be used to monitor the changes in bone resorption of the hind limb induced by tail-suspension. Male Wistar rats 5-weeks old were tail-suspended in a metabolic cage to unload the hind limbs. The control rats were not suspended. YH529 (YH), an inhibitor of bone resorption, or a vehicle (phosphate buffered saline=PBS) was administered daily starting 3 days before the commencement of tail-suspension. In the non-suspended rats receiving PBS, urinary excretion of D-Pyr did not show any significant change during the one-week experimental period. In the non-suspended rats receiving YH, D-Pyr excretion significantly decreased on day 5 and 7 when compared with that observed on day 0, in accordance with the systemic inhibition of bone resorption by YH. In the tail-suspended rats receiving PBS, D-Pyr excretion showed a tendency to increase on day 1, which is in agreement with our previous report that tail-suspension causes an early (on day 1 of suspension) and transient increase in bone-resorption of the hind limbs. In the tail-suspended rats treated with YH, the increase in D-Pyr excretion on day 1 was not observed, and a significantly lower excretion was noted from day 3 to 7 during the tail-suspension. It was suggested that D-Pyr excretion might reflect the transient increase in hind limb bone resorption induced by tail-suspension. As observed in-YH treated rats, D-Pyr excretion could serve as a good marker for the inhibition of systemic bone resorption.

Amino Acids↗
PubMed1998

[Congenital aortic regurgitation complicated by infective endocarditis of tricuspid valve due to spontaneous closure of ventricular septal defect: a case report].

A 32-year-old woman presented with a rare case of tricuspid valve endocarditis causing inflammatory reopening of the spontaneously closed ventricular septal defect (VSD), associated with aortic valve malformation. She was admitted to our hospital because of fever lasting 4 weeks. Severe aortic regurgitation was revealed by color Doppler echocardiography. Blood culture identified Microccus faecalis. Antibiotics were administered over 3 weeks, but serial echocardiography showed a developing vegetation in the right ventricle and left-to-right shunt flow. The diagnosis was infective endocarditis complicated by aortic ring abscess and interventricular septal fistula. Surgery performed on the 22nd hospitalized day found a vegetation of the tricuspid valve, a membranous type of VSD, and aortic valve malformation. Aortic valve replacement, patch closure of VSD, and tricuspid valvuloplasty achieved a successful outcome.

Adult↗
PubMed1998

[Functional analysis of nuclear hormone receptors].

Nuclear hormone receptors are transcription factors which regulate gene transcription by lipophilic hormones. The functional domains such as transactivation, DNA binding, ligand binding and dimerization are mapped in the distinct region of the receptors. To analyze these functions, ligand binding assay, gel shift assay, transfection study, GST pull-down method, immunoprecipitation method, two hybrid system and yeast functional assay are employed. These assays have been shown to clarify the molecular basis of the disorders which are due to mutation in the receptors.

Alleles↗
PubMed1998

[Thyroid hormone receptors and the disorders].

Thyroid hormone is essential for normal development and several metabolic pathways. Its action is mediated through its nuclear receptors (thyroid hormone receptors: TRs), which regulate gene transcriptions in a ligand-dependent manner. The abnormality of TR functions is linked with several disorders including resistance to thyroid hormone (RTH), malignancy and euthyroid sick syndrome. For example, mutant TRs were identified to cause RTH and a certain malignancy. The functionally impaired TRs might be related with euthyroid sick syndrome. The analyses of these TRs will elucidate the molecular mechanism or basis for the disorders, and may provide a new insight to find the way of diagnosis and treatment.

Animals↗
PubMed1998

[Pathogenesis of disorder due to thyroid hormone receptor mutation].

Thyroid hormone action is mediated through its nuclear receptor (thyroid hormone receptor; TR). A mutation in the TR causes resistance to thyroid hormone (RTH) with autosomal dominant inheritance. Using T3 binding assay, gel shift assay and transfection study, the pathogenesis of this disorder was elucidated at a molecular level. Mutant TRs lose their T3 binding activity, and inhibit wild type TR action in a dominant negative manner. For this dominant negative inhibition, the preservation of DNA binding and dimerization activities are required. It is indicated that the mutant TR complex competes with wild type TR complex for the DNA binding site to exert dominant negative inhibition. Thus, the functional analyses of mutant TRs are useful to elucidate the molecular basis of this disorder.

Humans↗
PubMed1997

Clinical and electrocardiographic profiles producing exercise-induced U-wave inversion in patients with severe narrowing of the left anterior descending coronary artery.

To elucidate which clinical features produce U-wave inversion, 339 patients with severe narrowing of the left anterior descending artery were evaluated. In patients with anterior myocardial infarction, extensive coronary artery disease and protected left anterior descending arterial territory are essential in the development of U-wave inversion, whereas electrocardiographic changes at rest in addition to anterior lead ST depression, rather than coronary anatomy, are important in those without anterior myocardial infarction.

Adult↗
PubMed1997

Effects of thyroid and glucocorticoid hormones on Kv1.5 potassium channel gene expression in the rat left ventricle.

The effects of thyroid and glucocorticoid hormones on the expression of the Kv1.5 potassium channel gene were studied in the rat left ventricle. Rats were rendered hypothyroid by oral administration of methimazole (MMI). Hyperthyroidism was induced in the MMI-treated rats by administration of L-thyroxine (T4). Kv1.5 mRNA levels decreased markedly in the hypothyroid rats, whereas they increased in the hyperthyroid rats. Propranolol, a beta-adrenergic blocker, did not inhibit the T4-dependent increase in Kv1.5 mRNA, indicating that the increase is not due to the increased beta-adrenergic stimuli under hyperthyroidism. Accordingly, treatment of the MMI-treated hypothyroid rats with isoproterenol, a beta-adrenergic receptor agonist, did not increase the mRNA. The Kv1.5 mRNA levels positively correlated with the thyroid hormone levels in sera. When rats were adrenalectomized and rendered hypothyroid, Kv1.5 mRNA become undetectable. Administration of 3,3',5-triiodothyronine (T3) at a dose to induce hyperthyroidism did not restore the mRNA level. However, T3 significantly increased the mRNA level when dexamethasone was co-administered at a physiological dose. These results for the first time demonstrate that thyroid hormone up-regulates Kv1.5 mRNA levels in the rat left ventricle and they demonstrate that glucocorticoid is required for this induction.

Animals↗
PubMed1997

Structure/function relationship of the cAMP response element in tyrosine hydroxylase gene transcription.

Expression of tyrosine hydroxylase (TH) is limited to catecholamine-producing neurons and neuroendocrine cells in a cell type-specific manner and is inducible by the cAMP-regulated signaling pathway. Previous results indicated that the cAMP response element (CRE) residing at -45 to -38 base pairs upstream of the transcription initiation site is essential for both basal and cAMP-inducible promoter activity of the 2.4-kilobase or shorter upstream sequence of the TH gene (Kim, K. S., Lee, M. K., Carroll, J. , and Joh, T. H. (1993) J. Biol. Chem. 268, 15689-15695; Lazaroff, M. , Patankar, S., Yoon, S. O., and Chikaraishi, D. M. (1995) J. Biol. Chem. 270, 21579-21589). Here, we further report that the CRE is critical for the promoter activity of the 5.6- or 9.0-kilobase upstream sequences of the rat TH gene, which had been shown to direct the cell-specific TH expression in vivo. To define the structure/function relationship of the CRE in transcriptional activation of the TH gene, we performed saturated mutational analyses of 12 nucleotides encompassing the CRE. Mutation of any nucleotide within the octamer motif results in a significant decrease of both basal and cAMP-inducible transcriptional activity of the TH reporter gene construct. Among the four nucleotides adjacent to the CRE (two 5' and two 3'), only the G residue at the immediate 3' position is important for full transcriptional activity. DNase I footprint analysis indicates a positive correlation between in vivo promoter activity and in vitro interaction between the CRE motif and its cognate protein factor(s). Reconstruction experiments using a TH promoter in which the native CRE was rendered inactive show that the CRE can transactivate transcription in either orientation through a window of approximately 200 base pairs upstream of the transcription initiation site, suggesting that CRE supports transcriptional activation of the TH gene in a distance-dependent manner. Finally, when the distance between the CRE and TATA box was changed by inserting an additional 5 or 10 bases, it was observed that both insertional mutations increased activity by approximately 3-fold. The cAMP inducibility was as intact as the wild type construct. Together, these results are consistent with a model in which transcriptional activation of the TH gene by the CRE requires that it be located within a certain proximity of the CAP site but does not depend on a stringent stereospecific alignment in relationship to the TATA element.

Animals↗
PubMed1997

Increase in Ref-1 mRNA and protein by thyrotropin in rat thyroid FRTL-5 cells.

Thyrotropin (TSH) induces the expression of fos and jun family genes in thyroid cells. The DNA-binding activity of these gene products (AP-1) has been shown to be enhanced by ubiquitous nuclear redox factor-1 (Ref-1). We thus examined whether TSH regulates Ref-1 gene expression in rat thyroid FRTL-5 cells. Northern blot analysis revealed that the abundance of Ref-1 mRNA significantly increased within 3 hours after TSH followed by a sustained increase until 12 hours. The increase was also induced by treatment with forskolin but not in the presence of cycloheximide, indicating that the TSH effect on Ref-1 mRNA is mediated by intracellular cAMP and requires de novo protein synthesis. Consistent with the elevation of the mRNA level, Western blot analysis showed an increase in Ref-1 protein 3 hours after TSH. The level continued to increase until 12 hours. These results suggested that increased Ref-1 by TSH might regulate the binding activity of AP-1 in thyroid cells. Considering that Ref-1 also has a DNA repair function, Ref-1 may play dual roles in gene regulation and DNA repair processes in thyroid cells.

Animals↗
PubMed1997

A splicing variant of Steroid Receptor Coactivator-1 (SRC-1E): the major isoform of SRC-1 to mediate thyroid hormone action.

Steroid Receptor Coactivator-1 (SRC-1) interacts with nuclear receptors only when they are bound to the ligands and enhance the transactivation. We identified splicing variants encoding three isoforms, SRC-1, SRC-1(-Q), and SRC-1E, generated by alternative usage of an exon(s) and splicing acceptor sites. RT-PCR analysis showed that SRC-1E was more abundantly expressed than SRC-1 or SRC-1(-Q) at the mRNA level in all the cell lines tested. SRC-1E lacks 56 amino acids of SRC-1 and has unique 14 amino acids at the carboxyl terminus, while SRC-1(-Q) differs from SRC-1 by deletion of only one glutamine residue. Since the C-terminal domain of SRC-1 has been shown to be involved in the interaction with nuclear receptors, the enhancement of transactivation by these three isoforms was tested. SRC-1E enhanced thyroid hormone dependent transactivation of reporter gene expression more profoundly than SRC-1 or SRC-1(-Q). Taken together, it was suggested that SRC-1E is the major isoform of SRC-1 to mediate thyroid hormone action.

Amino Acid Sequence↗
PubMed1997

Modification of thyroid hormone and 9-cis retinoic acid signaling by overexpression of their cognate receptors using adenoviral vector.

Tissue responsiveness to a hormone is dependent on the amounts of its receptor expressed under physiological conditions. In the present report, we compared the magnitude of ligand-dependent transactivation mediated by two nuclear hormone receptors, thyroid hormone receptor beta (TR) and retinoid X receptor alpha (RXR), when overexpressed in a variety of cell lines. TR, RXR and reporter (luciferase) genes under the control of artificial hormone response elements were introduced into the cells using recombinant adenovirus (Ad) vectors, to ensure highly efficient gene delivery. Although the amounts of TR expressed were similar in the cell lines infected with Ad-TR, T3 dependent induction of reporter gene expression was significantly greater in HepG2 than in Cos7, GH3, or JEG3 cells, indicating that factors other than TR are limiting the responsiveness to T3. The enhanced response to 9-cis retinoic acid in cells overexpressing RXR was much greater in JEG3 than in HepG2 which had the highest responsiveness to T3 under TR overexpression. These results indicate that the factors affecting T3 responsiveness are not identical to those affecting the 9-cis retinoic acid responsiveness. On the other hand, overexpression of RXR in addition to TR resulted in a decrease in T3-responsiveness in all the cell lines tested, suggesting that some cofactors are common to TR and RXR.

Adenoviridae↗
PubMed1997

Protooncogene expression in osteogenesis induced by bone morphogenetic protein.

In this study, changes in the expression of protooncogenes c-fos and c-myc messenger ribonucleic acid were investigated in mice after implantation of bone morphogenetic protein. The expression of c-fos showed a biphasic pattern. The first increase was observed on Day 1 with the aggregation of round cells. The second increase was observed on Day 7 with the appearance of chondroblasts. The amount of c-myc messenger ribonucleic acid showed the sustained high levels from Days 2 to 7. During this period, the proliferation of mesenchymal cells was histologically evident. After Day 11, the expression of c-fos and c-myc decreased and remained at low levels despite the progress in chondroosteogenesis. The protooncogenes c-fos and c-myc appear to increase before calcification in the process of bone morphogenetic protein induced bone and cartilage development.

Animals↗
PubMed1997

NGFI-B, c-fos, and c-jun mRNA expression in mouse brain after acute carbon monoxide intoxication.

The expression of immediate early genes (IEG) has been documented in the brain after various kinds of insults such as ischemia and hypoxia. To determine whether acute carbon monoxide intoxication (ACOI) might trigger IEG expression, adult ddY mice were subjected to carbon monoxide exposure at a rate of 30 mL/min for 35 seconds. The levels of NGFI-B, c-fos, and c-jun mRNA were determined by Northern blot analysis. A time-course study in the cerebral cortex indicated that the induction of NGFI-B, c-fos, and c-jun mRNA started as early as 15 minutes, reached a peak at 30 minutes, and returned to the basal level at 1 hour after the ACOI. In addition, the temporal feature of the induction of these IEG mRNA in the hippocampus was very similar to that in the cerebral cortex. Examination of brain regions at 30 minutes after the ACOI revealed a significant induction of NGFI-B mRNA in the cerebellum, thalamus-hypothalamus, brainstem. as well as in the cortex and hippocampus, but not in the striatum or olfactory bulb. Furthermore, the neuroanatomical distribution of c-fos mRNA at 30 minutes after the ACOI was very similar to that of the NGFI-B mRNA. The widespread distribution of these IEG in the brain, especially in the cerebellum and brainstem, indicates that the major cause for the triggering of IEG expression in the brain by the ACOI might be a diffuse hypoxia. These findings show for the first time the temporal and spatial expression of IEG in the brain after ACOI.

Acute Disease↗
PubMed1997

Levels of hepatocyte growth factor and its messenger ribonucleic acid in uncomplicated pregnancies and those complicated by preeclampsia.

The purpose of this study was to elucidate the possible relationship between hepatocyte growth factor (HGF) expression and the pathogenesis of preeclampsia. The concentration of immunoreactive HGF was measured and the expression of HGF messenger ribonucleic acid (mRNA) assessed in human placentas obtained from two groups: uncomplicated and preeclamptic pregnancies at various gestational weeks. In addition, the localization of HGF mRNA and c-met protein was analyzed using in situ hybridization and immunohistochemical staining, respectively. The expression of HGF mRNA and the concentration of immunoreactive HGF were highest in second trimester and were significantly decreased in preeclamptic placentas compared with the uncomplicated cases in third trimester. HGF mRNA was localized to placental mesenchymal cells, whereas c-met protein was demonstrated on cytotrophoblast. These results provide evidence of an abnormality of HGF expression in the preeclamptic placentas. Such placentas exhibit the abnormally shallow trophoblast invasion of the uterus, and reduced expression of HGF could well account for this morphometric change.

Blotting, Northern↗
PubMed1997

An enhanced method for measuring cardiac output using Doppler color flow echocardiography.

An enhanced method for determining cardiac output using Doppler color flow imaging techniques to measure mitral orifice diameter was developed and validated in an experimental model and in clinical patients. In an in vitro circuit model, color jet width correlated well with actual orifice dimension from 12 to 24 mm (r = 0.99). In the clinical application, mitral valve area was calculated as a X b X pi/4 where a and b represent the width of the color flow stream in the mitral orifice just distal to the annulus in apical long-axis (short-diameter) and 4-chamber (90 degrees rotated, long-diameter) views, respectively. Cardiac output was then computed as the product of mitral valve area and time-velocity integral of transmitral flow from the same site. Cardiac output was also measured by thermodilution and conventional echocardiographic methods using diameters and time-velocity integrals from the left ventricular outflow tract. In 30 patients with nonvalvular heart disease, cardiac output measured by thermodilution ranged from 3.40 to 8.40 L/min. Cardiac output was determined in 28 of 30 patients (93%) by the Doppler color flow imaging technique; it ranged from 3.00 to 8.36 L/min and correlated well with thermodilution: y = 0.90x + 0.63, r = 0.91. Cardiac output was determined in 24 of 30 patients by the conventional left ventricular outflow method (80%). The cardiac output measured by the conventional method correlated less closely with thermodilution (r = 0.84), although there was no statistical difference in correlation coefficiencies between the 2 methods. These results indicate that the Doppler color flow imaging technique can be used to enhance the determination of cardiac output by echocardiography, particularly when the conventional method has resulted in technically inadequate recordings.

Adult↗
PubMed1997

Changes in urinary excretion of pyridinium cross-links during Spacelab-J.

In SLJ-1 we proposed to study three major objectives. They were; 1. hormonal changes associated with fluid and electrolyte metabolism, 2. the effect of space flight on the circadian rhythms of endocrine and metabolic systems, 3. the changes in the indices of the bone and muscle metabolism during space flight. In this report, the changes in the bone metabolism during Spacelab-J will be presented with a special emphasis on urinary excretion of pyridinium cross-links. Timed urine samples from three Japanese payload specialists were obtained for 3 days from May 19 to 21, 1991 (one year before the launch = L-1 year). Immediately before the launch (L-3 to L-0), urine samples were obtained from a payload specialist who was on board the Space Shuttle Endeavor (PS). During the inflight period (flight from September 3 to 10 in 1992), urine samples from the PS were collected by using Urine Monitoring System (UMS). After the landing, they were obtained from the PS for three days (R+0-R+2). Various parameters related to bone metabolism such as hydroxyproline, pyridinium cross-links and calcium were determined. It was noted that excretion of hydroxyproline decreased during the preflight periods when compared with that in the control L-1 year period. The average excretory rate during control period was 846.2 +/- 198.7 milligrams/hour (mean +/- SD), while those in the preflight 474.6 +/- 171.1 milligrams/hour, suggesting the diminished collagen intake during the preflight period. Average excretion rate of pyridinium cross-links during the first 4 mission days (MD0-MD3) was similar to that of preflight and control L-1 year period. However, it was significantly increased during the last 4 mission days (MD4-MD7). It returned to the preflight level during postflight days (R+0-R+2). Increased urinary excretion of calcium during the last 4 mission days were also observed. These results suggest that increase in bone resorption could occur during relatively short stay in microgravity.

Aerospace Medicine↗
PubMed1997

[Usefulness of dipyridamole thallium scintigraphy in the diagnosis of coronary artery disease in elderly patients].

Patients suspected of having coronary artery disease (CAD) underwent dipyridamole thallium scintigraphy, exercise electrocardiography, and coronary angiography. Of the 500 patients studied, 163 were at least 65 years old, and 337 were less than 65 years old. Both CAD and multivessel CAD were more common in elderly than in younger patients (81% vs 69%, p < 0.01 for CAD; and 43% vs 26% p < 0.01 for multivessel CAD). In patients without myocardial infarction, the specificity of exercise electrocardiography was lower among elderly patients than among younger patients (52% vs 61%), but the sensitivity was higher (87% vs 75%). In contrast, both the sensitivity and the specificity of dipyridamole thallium scintigraphy were similar in the two age groups (86% vs 87% and 79% vs 74%). Among patients with myocardial infarction and a positive exercise test, reversible defects were equally common in the two age groups (60% vs 58%). The reversible defects were in areas remote from the area of infarction in half of the patients in both groups. Among patients with negative exercise-test results, reversible defects were more common in elderly patients than in younger patients (57% vs 38%). The reversible defects were in the infarcted area in 71% and 79% of these patients, respectively. These results indicate that dipyridamole thallium scintigraphy is a sensitive and specific method for detecting CAD, independent of age. It is particularly useful in identifying myocardial viability in the infarcted area.

Adult↗