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Biomedical subjects

H S Choi

Publications and source records attributed to H S Choi.

At least 127 records · Page 7Linked to original sources
PubMed1996

An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors.

SHP is an orphan member of the nuclear hormone receptor superfamily that contains the dimerization and ligand-binding domain found in other family members but lacks the conserved DNA binding domain. In the yeast two-hybrid system, SHP interacted with several conventional and orphan members of the receptor superfamily, including retinoid receptors, the thyroid hormone receptor, and the orphan receptor MB67. SHP also interacted directly with these receptors in vitro. In mammalian cells, SHP specifically inhibited transactivation by the superfamily members with which it interacted. These results suggest that SHP functions as a negative regulator of receptor-dependent signaling pathways.

Amino Acid Sequence↗
PubMed1996

A component of the 26S proteasome binds on orphan member of the nuclear hormone receptor superfamily.

The 26S proteasome complex plays a general role in turnover of both short and long lived proteins by specifically degrading ubiquitinated proteins. Recent evidence suggests that this large protease has more specific functions in a number of important cellular processes, ranging from activation of the transcription factor NFkB and antigen processing to transit through mitosis. We have identified a component of the 26S proteasome that interacts specifically with MB67, an orphan member of the nuclear hormone receptor superfamily. MIP224 (MB67 interacting protein) was isolated using the yeast two hybrid system and is apparently identical to the human 26S proteasome component TBP7. MIP224/TBP7 is one of several proteasomal proteins that share a strongly conserved ATPase domain (CAD) which is also present in a rapidly expanding superfamily of proteins with diverse functions. In yeast, MIP224 interacts specifically with MB67 and another closely related orphan receptor, but does not interact with several other receptor superfamily members tested. In mammalian cells, coexpression of MIP224 inhibits transactivation by MB67. MIP224 also interacts in yeast with other CAD proteins, including MSS1, which is proteasomal, and TRIP1, which is associated with transcriptional activation. This interaction of a proteasomal protein with a transcriptional protein suggests a previously unexpected link between the processes of protein degradation and transcriptional regulation.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1995

Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors.

We have used a yeast genetic system to isolate cDNAs encoding proteins that specifically interact with the ligand-binding domain of human retinoid X receptor-alpha (RXR alpha). A number encoded portions of two known RXR heterodimer partners, the retinoic acid receptor (RAR) and the peroxisome proliferator activated receptor. Of four additional RXR-interacting proteins (RIPs) selected for further study two, RIP14 and RIP15, are previously unidentified orphan members of the nuclear receptor superfamily. Two others, RIP110 and RIP13, do not show significant similarities to previously reported proteins. RIP110 interacts with LexA-RXR only in yeast cells grown in the presence of the RXR ligand 9-cis-RA, while the interaction of the four receptor superfamily members and RIP13 is unaffected by the presence or absence of 9-cis-RA. RIP110 and RIP13 also interact in yeast with several other members of the receptor superfamily, but RIP14 and RIP15 interact only with RXR. Analysis of larger cDNA clones demonstrates that there are at least two isoforms of RIP14 that differ in the N-terminal (A and B) and hinge (D) domains. Northern blot analysis indicates that RIP14 is expressed specifically in liver and kidney, while RIP15 is expressed in every tissue tested. Both RIP14 and 15 bind as heterodimers with RXR to the RA response element (RARE) from the promoter of the RAR beta 2 isoform (the beta RARE), and RIP14 and RXR heterodimers also bind the ecdysone response element from the Drosophila heat shock protein 27 promoter. Both heterodimers also bind to several synthetic RAREs and other elements. In cotransfections, neither RIP14 nor RIP15 trans-activates a reporter containing multiple copies of the beta RARE under any of a variety of conditions, suggesting that their activities are dependent on the binding of as yet unidentified specific ligands or on activation by other processes.

Amino Acid Sequence↗
PubMed1995

Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor.

The thyroid hormone (T3) receptors (TRs) are hormone-dependent transcription factors that regulate expression of a variety of specific target genes. To help elucidate the mechanisms that underlie this transcriptional regulation and other potential TR activities, we used the yeast interaction trap to isolate clones encoding proteins that specifically interact with the ligand binding domain of the rat TR beta. Several such proteins, called Trips (TR-interacting proteins), were isolated from independent selections carried out either in the presence or absence of T3. Surprisingly, all of the Trips were dependent on hormone for interaction with the TR, with some interacting only when T3 is present and others only when it is absent. Nearly all of the Trips also show similar ligand-dependent interaction with the retinoid X receptor (RXR), but none interact with the glucocorticoid receptor under any conditions. The sequences of three of the Trips predict specific functional roles: one is an apparent human homolog of a yeast transcriptional coactivator, one is a new member of a class of nonhistone chromosomal proteins, and one contains a conserved domain associated with ubiquitination of specific target proteins. Consistent with the pleiotropic effects of TR and RXR, several other Trips show significant amino acid sequence similarity with proteins involved in various regulatory pathways. The inherent transcriptional activity of the Trips was tested in yeast, and a chimeric protein consisting of a fusion of Trip4 to the bacterial LexA repressor protein is a relatively strong transcriptional activator. Similar LexA fusions to Trip9 and Trip10 had no transcriptional activity on their own but, when coexpressed with both TR and RXR, conferred T3-dependent activation to a reporter gene controlled by LexA binding sites. We suggest that this indirect T3 response provides a novel mechanism for hormonal activation of gene expression, and that studies of the Trips will provide important insights into the specific mechanisms of action of TRs and other receptors.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1995

Function of the interarytenoid(IA) muscle in phonation: in vivo laryngeal model.

Thyroarytenoid(TA), lateral cricoarytenoid(LCA), and IA muscles are referred to as the adductors of the vocal fold. The TA is known to shorten the vocal folds and to adduct the membranous vocal fold, and the LCA adducts the inter-vocal process region and IA adducts the posterior commissure. Even though IA has an important role for the positioning of the vocal folds during respiration and phonation together with the action of the posterior cricoarytenoid muscle, little is known about the effect of IA on voice parameters during phonation. An in vivo canine model was used in five mongrel dogs to examine the role of the IA muscle in controlling phonation. In two out of five dogs, sound could not be elicited without stimulating the IA branches of the recurrent laryngeal nerves. When the IA was dynamically and statistically stimulated, subglottic pressure, vocal intensity and fundamental frequency were increased. However, open quotient was not changed markedly. These results suggest that the IA affects the voice parameters mainly by controlling subglottic pressure during phonation.

Animals↗
PubMed1994

The disappearing kidney. A case of emphysematous pyelonephritis.

We describe a case of bilateral emphysematous pyelonephritis in which the left kidney could not be visualized sonographically because of multiple irregular air-fluid interfaces. This observation, which to our knowledge has been noted only once before in the literature, may be a diagnostic clue to this potentially fatal disease.

Acute Disease↗
PubMed1994

A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements.

We have identified and characterized a new orphan member of the nuclear hormone receptor superfamily, called MB67, which is predominantly expressed in liver. MB67 binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes, both of which consist of a direct repeat hexamers related to the consensus AGGTCA, separated by 5 bp. MB67 binds these elements as a heterodimer with the 9-cis-retinoic acid receptor, RXR. However, MB67 does not bind or activate other retinoic acid response elements with alternative hexamer arrangements or any of several other wild-type and synthetic hormone response elements examined. The transactivation of retinoic acid response elements by MB67 is weaker than that conferred by the retinoic acid receptors but does not require the presence of all-trans retinoic acid, 9-cis-retinoic acid, or any exogenously added ligand. We propose that MB67 plays an important role in the complex network of proteins that govern response to retinoic acid and its metabolites.

Amino Acid Sequence↗
PubMed1994

A new orphan member of the nuclear hormone receptor superfamily closely related to Rev-Erb.

We have isolated complementary DNA clones encoding a novel orphan member of the nuclear receptor superfamily, termed BD73. This protein shows strong amino acid sequence similarity to the previously described Rev-ErbA alpha. Unlike Rev-Erb, in which the opposite strand of the C-terminal coding region encodes the C-terminal portion of a variant thyroid hormone receptor isoform, the opposite strand of the C-terminal coding region of BD73 does not have any extensive open reading frames. BD73 messenger RNA is expressed in a wide variety of tissues and cell lines. In quiescent HepG2 cells, BD73 messenger RNA levels are strongly induced by planar aromatic antioxidants. Like Rev-Erb, BD73 binds as a monomer to a DNA sequence which consists of a specific A/T-rich sequence upstream of the consensus hexameric half-site specified by the P box of the DNA-binding domain. Amino acid sequence comparisons suggest that the A box sequence, which has been suggested to mediate monomer binding by other superfamily members, lies closer to the DNA-binding domain in BD73 and Rev-Erb than in other receptors. Under the conditions examined, neither BD73 nor Rev-Erb activated reporters containing multiple copies of their common binding site. Thus, these two orphans may require an as yet unidentified ligand or other signal for such activation. Together, BD73 and Rev-Erb define a subgroup of orphan receptors that bind as monomers to a half-site flanked by a specific and extended A/T-rich sequence.

Amino Acid Sequence↗
PubMed1993

Immunoelectron microscopy identification of early proliferating cells in rat liver tissue during hyperplasia induced by lead nitrate.

Recent studies have suggested that hepatic stem cells may be involved in at least some forms of liver epithelial growth. To obtain further information on this controversial hypothesis, we treated rats with lead nitrate to induce liver growth and identified the cells undergoing early DNA synthesis by bromodeoxyuridine immunohistochemistry, using both light and electron microscopic detection methods. Eight hours after an intravenous injection of lead nitrate 100 mumol/kg, DNA synthesis was detected in a few scattered hepatocytes and in nonparenchymal cells in portal connective tissue. At the light microscopic level, identification of nonparenchymal cells was limited to bile duct epithelial cells. Other cell types were also labeled, but their identity could not be established. At the ultrastructural level, however, four types of nonparenchymal cells were identified as containing bromodeoxyuridine immunogold particles. These four types included bile duct epithelial cells, fibroblasts, macrophages and nondescript periductular cells. These periductular cells displayed certain ultrastructural features of bile duct cells but did not line a lumen or display microvilli on their apical membrane, nor did they reside within the bile duct basement membrane. Because proliferation of nonparenchymal cells in portal areas preceded that of hepatocytes, it is suggested that the former reaction reflects a direct mitogenic effect of lead nitrate and not an adaptive growth response secondary to parenchymal enlargement. However, whether DNA synthesis in periductular cells or bile duct cells reflects activation of hepatic stem cells cannot be established from the present morphological observations. If so, such a progenitor compartment must be dormant because it does not seem to play a functional role in this and other forms of adult liver epithelial growth.

Animals↗
PubMed1993

Progressive impairment of monocytic function in HIV-1-infected human macrophage hybridomas.

Using human macrophage hybridomas infected with HIV-1, we investigated monocyte function over a 5-week period after HIV-1 infection. Two clones, 63 and 30, were infected with HIV-1IIIB. Infection was documented by RT activity (15 x 10(6) cpm/ml), intracytoplasmic staining with an anti-p24 antibody, in situ hybridization with an HIV-1-specific riboprobe, and electron microscopy showing intracytoplasmic virus. Two weeks after infection, clones 63 and 30 lost expression of all class II antigens (DR, 81.7 vs. 0%; DQ, 15.6 vs. 0%; and DP, 76.9 vs. 0%) while retaining expression of class I (87.4 vs. 84.1%), LFA-1 (82.4 vs. 83.1%), and LFA-3 (79.1 vs. 74.7%) antigens when compared to uninfected cells. When tested for functional integrity, infected but not uninfected clone 63 cells failed to stimulate a tetanus-specific MHC-restricted T cell proliferative response 2 weeks after infection. Cytokine secretion and antigen processing were also perturbed as production of IL-1 was abolished 2 weeks after infection (although IL-6 secretion was augmented) and infected clone 63 cells failed to process exogenous antigen. Last, the viability of T cells cocultured with infected clone 63 was dramatically decreased 35 days after infection (85 vs. 15%). There was no evidence of transmission of HIV-1 to T cells, suggesting a toxic effect of infected clone 63. Taken together, these data suggest that altered macrophage function in our system occurs at multiple levels, which may account for the early immunological defects described in HIV-1 infection.

Antigen-Presenting Cells↗
PubMed1993

Metastatic meningioma. Hemangiopericytoma or angioblastic meningioma?

The question of whether meningeal hemangiopericytoma is a variant of meningioma ("angioblastic meningioma") or a nosologically distinct entity remains controversial. We present the case histories of an intracranial meningioma and of a meningeal hemangiopericytoma, both of which developed extracranial metastases. The metastatic lesions in both cases were studied by electron microscopy, which demonstrated pericytomatous differentiation in one instance and meningothelial differentiation in the other. This report supports the opinion that meningeal hemangiopericytomas and meningiomas of the CNS are distinct pathological entities.

Adult↗
PubMed1993

A new method for computed tomography image compression using adjacent slice data.

RATIONALE AND OBJECTIVES: The authors developed and subjectively evaluated an interslice compression algorithm that explores the redundancy among adjacent slices of an x-ray computed tomography (CT) scan. This algorithm has been compared to an intraslice compression algorithm based on the two-dimensional discrete cosine transform. METHODS: Nine x-ray CT head images from three patients were compressed with this interslice method at compression ratios of 5:1, 10:1, and 15:1. The same images were also compressed with the intraslice method at the same ratios. Six radiologists judged quality of randomly selected compressed and decompressed images compared to that of the originals. The evaluation data were analyzed statistically with the analysis of variance and Tukey's multiple comparison. Kappa-like statistics (Williams index and O'Connell and Dobson indexes) were also calculated to measure the agreement among readers beyond the amount expected by chance. RESULTS: The interslice coding algorithm showed significantly better quality than the intraslice method at significance level 0.05, even though there was no difference in the objective distortion measure (signal-to-noise ratio). Also, the quality of 10:1 compressed images with the interslice coding algorithm was not significantly different from that of the originals at level 0.05. While large variations in agreement occurred among readers, the overall agreement was statistically significant. CONCLUSIONS: By using adjacent slice information in compressing x-ray CT images, significantly better quality in compressed and decompressed images was achieved. While 10:1 compressed images with the interslice algorithm were not significantly different from the originals in quality at level 0.05, effect on diagnostic accuracy remains to be investigated.

Algorithms↗
PubMed1993

Treatment failure in malignant gestational trophoblastic disease.

One hundred and thirty-three patients with malignant gestational trophoblastic disease (GTD) were admitted. All patients (86/86) of the nonmetastatic and metastatic low-risk groups and 89.4% (42/47) of the metastatic high-risk group showed remission. The overall remission rate was 96.2%. Among 5 patients with brain metastases, however, only one (20%) survived. We arrived at two main conclusions. First, brain metastatic lesions did not successfully respond to therapy utilizing conventional chemotherapeutic regimens. Second, the key factors for successful outcome in brain metastases were early diagnosis and aggressive initial therapy. Therefore, early detection of brain metastases should be made with: (1) fine computerized tomography (CT) or magnetic resonance imaging (MRI), (2) measurement of the ratio of serum to cerebrospinal fluid hCG concentration, and (3) early recognition of their clinical features.

Adult↗
PubMed1993

Function of the thyroarytenoid muscle in a canine laryngeal model.

Fundamental frequency is controlled by contraction of the thyroarytenoid (TA) and cricothyroid (CT) muscles. While activity of the CT muscle is known to tense and thin the vocal folds, little is known about the effect of the TA muscle on vocal fold vibration. An in vivo canine laryngeal model was used to examine the role of the TA muscle in controlling phonation. Isolated TA muscle activation was obtained by stimulating sectioned terminal TA branches through small thyroid cartilage windows. Subglottic pressure measures, electroglottographic and photoglottographic signals, and acoustic signals were obtained in 5 mongrel dogs during dynamic and static variations in TA muscle activity. Results indicated that TA muscle activation is a major determinant in sudden shifts from high-frequency to modal phonation. Subglottic pressure increased and open quotient decreased gradually with increasing TA activation.

Animals↗
PubMed1993

Function of the posterior cricoarytenoid muscle in phonation: in vivo laryngeal model.

The function of the posterior cricoarytenoid (PCA) muscle in phonation has not been well documented. To date, several electromyographic studies have suggested that the PCA muscle is not simply an abductor of the vocal folds, but also functions in phonation. This study used an in vivo canine laryngeal model to study the function of the PCA muscle. Subglottic pressure and electroglottographic, photoglottographic, and acoustic waveforms were gathered from five adult mongrel dogs under varying conditions of nerve stimulation. Subglottic pressure, fundamental frequency, sound intensity, and vocal efficiency decreased with increasing stimulation of the posterior branch of the recurrent laryngeal nerve. These results suggest that the PCA muscle not only acts to brace the larynx against the anterior pull of the adductor and cricothyroid muscles, but also functions inhibitorily in phonation by controlling the phonatory glottal width.

Animals↗
PubMed1993

Induction of c-fos and c-jun gene expression by phenolic antioxidants.

We have found that phenolic antioxidants specifically induce expression of the c-fos and c-jun protooncogenes. After treatment of quiescent human hepatoma HepG2 cells with butylated hydroxytoluene, butylated hydroxyanisole, or other phenolic antoxidants, the levels of c-fos and c-jun mRNAs are substantially increased. This response is antioxidant specific, dose dependent, and transient, with maximal levels at 3-6 h. The antioxidant-specific induction of c-fos/CAT promoter constructs in transient transfections indicates that at least a portion of this response is transcriptional. Deletions and point mutations map sequences required for the antioxidant response of the c-fos promoter to the serum response element. The antioxidant-specific induction of expression directed by a reporter plasmid containing four AP-1 sites and the induction of AP-1 DNA-binding activity confirm previous results indicating that antioxidant treatment increases AP-1 activity.

Antioxidants↗
PubMed1993

Polypoid adenosquamous carcinoma of the esophagus with prominent spindle cells. Report of a case with immunohistochemical and ultrastructural studies.

We report a case of spindle-cell adenosquamous carcinoma of the esophagus. This represents the third case in the worldwide literature in which an esophageal polypoid tumor contains adenosquamous carcinoma rather than the usual squamous cell carcinoma in addition to a prominent spindle-cell element. The spindle-cell component displayed positive immunoreaction for both keratin and vimentin, as expression of bidirectional differentiation within a single neoplasm.

Adenocarcinoma↗