Search PubMed⌕ Search

Biomedical subjects

T K Kim

Publications and source records attributed to T K Kim.

At least 91 records · Page 5Linked to original sources

Critical role of the second stirrup region of the TATA-binding protein for transcriptional activation both in yeast and human.

We previously identified three TATA-binding protein (TBP) point mutations (L114K, L189K, and K211L) that have severe effects on transcriptional activation by acidic activators, but no effect on basal transcription, in a yeast-derived TBP-dependent in vitro transcription system (Kim, T. K., Hashimoto, S., Kelleher, R. J., III, Flanagan, P. M., Kornberg, R. D., Horikoshi, M., and Roeder, R. G. (1994) Nature 369, 252-255). These activation defects were also demonstrated in vivo in yeast cells (Lee, M., and Struhl, K. (1995) Mol. Cell. Biol. 15, 5461-5469). Here, the transcriptional activities of these and other TBP mutations were examined in human by both in vitro and in vivo assays. Mutations L189K and E188K, which lie in the second stirrup region of TBP, show defective activation by acidic activators both in yeast and human. Somewhat surprisingly, mutations L114K and K211L have almost no demonstrable effect on activation by acidic activators in human, in contrast to their severe effects on defective activator responses in yeast. The implications of these results for TBP structure and function are discussed.

DNA-Binding Proteins↗

Re-evaluation of optimal dose of contrast medium for vascular enhancement in CT of the head and neck.

Adequate contrast enhancement of major neck vessels is more important than that of a tumour itself in CT of most head and neck tumours because of differentiation from neck node metastases. Our purpose was to re-evaluate the dosage of contrast medium for adequate vascular enhancement in CT of the head and neck. In a blind prospective fashion, 60 patients with a variety of head and neck lesions were randomised into three equal groups receiving 0.75, 1.0, or 1.25 ml/kg of meglumine ioglycate, 300 mg/ml. Contrast medium was administered by injector at 2 ml/s. The scan time and interscan delay were each 1 s, and total scan time 50-180 s. The scan was started immediately after administration of two-thirds of the contrast medium. The degree of vascular enhancement was assessed visually and quantitatively. We visually scored the degree of vascular enhancement as excellent (4 points), good (3), fair (2) or poor (1). For quantitative study, after measuring the CT numbers of the common or internal carotid artery (CA), internal jugular vein (IJV) and adjacent muscle at three levels, were calculated mean vessel/muscle contrast ratios. The degree of enhancement of the CA and IJV tended to increase with dose of the contrast media, but no examination was rated as showing poor enhancement in any group. The mean visual assessment scores for 0.75, 1.0, and 1.25 ml/kg were 2.7, 2.9 and 3.1, respectively; the mean ICA/muscle contrast ratios were 1.58, 1.55 and 1.63, and those of IJV/ muscle 1.65, 1.59 and 1.59. There was no significant difference between visual and quantitative assessment in any group. The results suggest that 0.75 ml/kg of contrast medium appears sufficient for vascular opacification for head and neck lesions when the CT scan can be completed in about 120 s.

Adolescent↗

The mechanism of transcriptional synergy of an in vitro assembled interferon-beta enhanceosome.

A functional interferon-beta gene enhanceosome was assembled in vitro using the purified recombinant transcriptional activator proteins ATF2/c-JUN, IRF1, and p50/p65 of NF-kappa B. Maximal levels of transcriptional synergy between these activators required the specific interactions with the architectural protein HMG I(Y) and the correct helical phasing of the binding sites of these proteins on the DNA helix. Analyses of the in vitro assembled enhanceosome revealed that the transcriptional synergy is due, at least in part, to the cooperative assembly and stability of the complex. Reconstitution experiments showed that the formation of a stable enhanceosome-dependent preinitiation complex require cooperative interactions between the enhanceosome; the general transcription factors TFID, TFIIA, and TFIIB; and the cofactor USA. These studies provide a direct biochemical demonstration of the importance of the structure and function of natural multicomponent transcriptional enhancer complexes in gene regulation.

Activating Transcription Factor 2↗

Optimal MR protocol for hepatic hemangiomas. Comparison of conventional spin-echo sequences with T2-weighted turbo spin-echo and serial gradient-echo (FLASH) sequences with gadolinium enhancement.

PURPOSE: To compare conventional spin-echo (SE) sequences with T2-weighted turbo SE and serial gadolinium-enhanced T1-weighted FLASH sequences in the detection and characterization of hepatic hemangiomas, and to describe the enhancement characteristics of the lesions on dynamic MR imaging. MATERIAL AND METHODS: Forty-two patients with 66 hemangiomas were studied at 1.0 T or 1.5 T by using conventional SE sequences (T1-weighted, T2-weighted, and heavily T2-weighted), T2-weighted turbo SE sequences, and breath-hold T1-weighted FLASH sequences acquired before, immediately after, and 1, 2, 3, 5, and 10 min after injection of a bolus of gadopentetate dimeglumine. Images were quantitatively analyzed for lesion-to-liver contrast-to-noise (C/N) ratios, and qualitatively analyzed for lesion conspicuity. The enhancement pattern and the rapidity of enhancement were analyzed in small (<15 mm), medium (15-39 mm), and large (>39 mm) hemangiomas. RESULTS: In T2-weighted images, T2-weighted turbo SE and heavily T2-weighted SE images had higher C/N ratios than T2-weighted SE images (p=0.003). Lesion conspicuity was not significantly different in these 3 sequences (p=0.307). In T1-weighted images, T1-weighted FLASH images had higher C/N (p<0.001) and also better lesion conspicuity (p<0.001) than T1-weighted SE images. Immediate uniform enhancement was seen in 43% of small hemangiomas (9 of 21 lesions), and persistent central hypointensity was seen in 73% of large hemangiomas (11 of 15 lesions). Rapid enhancement was seen in 62% of small hemangiomas (13 of 21 lesions) and in 31% of medium or large hemangiomas (14 of 45 lesions). CONCLUSION: Further clinical study is needed for evaluating the differential diagnostic advantages of turbo SE T2-weighted imaging compared to the calculation of T2-values by means of a SE T2-weighted sequence. However, the results of the present study suggest that T2-weighted turbo SE imaging and precontrast and serial gadolinium-enhanced FLASH imaging have the potential to replace conventional SE imaging in the evaluation of hepatic hemangiomas.

Contrast Media↗

Peripheral cholangiocarcinoma of the liver: two-phase spiral CT findings.

PURPOSE: To determine characteristic features of peripheral cholangiocarcinoma on two-phase spiral computed tomographic (CT) scans. MATERIALS AND METHODS: Thirty-four patients with peripheral cholangiocarcinoma underwent two-phase spiral CT. Hepatic arterial phase and portal venous phase images were obtained 30 and 65 seconds, respectively, after the start of contrast material infusion. RESULTS: Thin, mild, incomplete rimlike contrast enhancement at the tumor periphery was seen on CT scans from both phases in 23 patients. Thick, continuous rimlike contrast enhancement and marked homogeneous contrast enhancement were present on scans in four patients and one patient, respectively. No definite contrast enhancement pattern was seen on scans in six patients. Other findings included increased lobar or segmental hepatic attenuation in adjacent normal liver during the arterial phase (n = 10), markedly low attenuation with amorphous areas of slightly high attenuation in the tumor during both phases (n = 33), internal septumlike linear structures (n = 8), narrowing or obstruction of the portal vein as it traversed the tumor (n = 16), and a patent hepatic vein (n = 4). CONCLUSION: Thin, mild, incomplete rimlike contrast enhancement at the tumor periphery and markedly low intratumoral attenuation with amorphous areas of slightly high attenuation during both scanning phases are typical findings of peripheral cholangiocarcinoma.

Bile Duct Neoplasms↗

High-resolution mapping of nucleoprotein complexes by site-specific protein-DNA photocrosslinking: organization of the human TBP-TFIIA-TFIIB-DNA quaternary complex.

We have used a novel site-specific protein-DNA photocrosslinking procedure to define the positions of polypeptide chains relative to promoter DNA in binary, ternary, and quaternary complexes containing human TATA-binding protein, human or yeast transcription factor IIA (TFIIA), human transcription factor IIB (TFIIB), and promoter DNA. The results indicate that TFIIA and TFIIB make more extensive interactions with promoter DNA than previously anticipated. TATA-binding protein, TFIIA, and TFIIB surround promoter DNA for two turns of DNA helix and thus may form a "cylindrical clamp" effectively topologically linked to promoter DNA. Our results have implications for the energetics, DNA-sequence-specificity, and pathway of assembly of eukaryotic transcription complexes.

Adenoviruses, Human↗

Regulation of interferon-gamma-activated STAT1 by the ubiquitin-proteasome pathway.

STAT proteins (signal transducers and activators of transcription) are latent cytoplasmic transcription factors that are phosphorylated by Janus kinases in response to cytokines. Phosphorylated STAT proteins translocate to the nucleus, where they transiently turn on specific sets of cytokine-inducible genes. The mechanism that controls the amounts of activated STAT proteins is not understood. STAT1 proteins activated by interferon-gamma treatment in HeLa cells were shown to be stabilized by a proteasome inhibitor and ubiquitinated in vivo. Thus, the amount of activated STAT1 may be negatively regulated by the ubiquitin-proteasome pathway.

Cell Nucleus↗

Power versus conventional color Doppler sonography: comparison in the depiction of vasculature in liver tumors.

PURPOSE: To compare power and conventional color Doppler sonography in the depiction of the intratumoral vasculature of hemangiomas, hepatocellular carcinomas (HCCs), and metastases of the liver. MATERIALS AND METHODS: Thirty-two patients with liver tumors (12 hemangiomas, 11 HCCs, and nine metastases) were prospectively evaluated with power and conventional color Doppler sonography by using a 2-4-MHz convex probe with 2-MHz Doppler frequency. Power Doppler sonography was performed with a 75%-88% gain. Conventional color Doppler sonography was performed with a 55%-75% gain and a pulse repetition frequency of 700 Hz. Power Doppler signals and color Doppler signals interrogated in one plane were analyzed by two radiologists, who subjectively rated power Doppler sonography as superior, equal, or inferior to color Doppler sonography. RESULTS: Overall, power Doppler sonography was superior to color Doppler sonography in 18 patients and equal in 14 (P < .01). In hemangiomas, power Doppler sonography was superior to color Doppler sonography in 10 patients and equal in two (P < .01). In HCCs, power Doppler sonography was superior to color Doppler sonography in four patients and equal in seven (P > .05). In metastases, power Doppler sonography was superior to color Doppler sonography in four patients and equal in five (P < .05). CONCLUSION: Power Doppler sonography is more sensitive than color Doppler sonography in the depiction of the vasculature of liver tumors, particularly in hemangiomas.

Adult↗

TATA-binding protein residues implicated in a functional interplay between negative cofactor NC2 (Dr1) and general factors TFIIA and TFIIB.

The TATA-binding protein (TBP) plays a key role in transcription initiation. Several negative cofactors (NC1, NC2, and Dr1) are known to interact with TBP in a manner that prevents productive interactions of transcription factors TFIIA and TFIIB with promoter-bound TBP. To gain insights into the regulatory interplay on the surface of TBP, we have employed mutant forms of TBP to identify amino acid residues important for interactions with the negative regulatory cofactor NC2 and the general factor TFIIB. The results show the involvement of distinct domains of TBP in these interactions. Residues (Lys-133, Lys-145, and Lys-151) in the basic repeat region are important for interactions with NC2, as well as with TFIIA (Buratowski, S., and Zhou, H. (1992) Science 255, 1130-1132; Lee, D. K., DeJong, J., Hashimoto, S., Horikoshi, M., and Roeder, R. G. (1992) Mol. Cell. Biol. 12, 5189-5196), whereas a residue (Leu-189) in the second stirrup-like loop spanning S2' and S3' is required for interaction with TFIIB. In addition, we demonstrate that NC2 is identical to the previously cloned negative cofactor Dr1. The implications of these results for TBP structure and function are discussed.

Binding Sites↗

Intracranial tuberculoma: comparison of MR with pathologic findings.

PURPOSE: To compare the MR signal intensity patterns and enhancement pattern of intracranial tuberculomas with their histopathologic features. METHODS: MR images of six patients with surgically proved intracranial tuberculoma were reviewed retrospectively and were compared with histologic findings of the resected specimen. Detailed histologic examination was performed to look for the extent and characteristics of caseation necrosis, fibrosis, and inflammatory cellular infiltrates at each area of different signal intensities and at the enhancing areas on MR. Signal intensities for T1- and T2-weighted images were compared with normal gray matter. RESULTS: On T1-weighted images, the granulomas showed a slightly hyperintense rim surrounded by a complete or partial rim of slight hypointensity and central isointensity or mixed isointensity and hyperintensity in five patients and homogeneous isointensity in one patient. Histologically, the zone of central isointensity or mixed intensity corresponded to caseation necrosis plus adjacent cellular infiltrates. The hyperintense and hypointense rims corresponded to the layers of collagenous fiber and the layers of the inflammatory cellular infiltrates, respectively. On T2-weighted images, the entire portion of the granuloma showed slightly heterogeneous isointensity or hypointensity with small markedly hypointense foci in five patients, and a hyperintense center surrounded by a hypointense rim in one patient. Histologic layers were not discriminated on T2-weighted images. On postcontrast T1-weighted images, there were single or multiple conglomerate ring enhancements within a tuberculoma in all six patients, corresponding to the layers of both collagenous and inflammatory cells. CONCLUSION: Combination of the described signal intensity patterns and conglomerate ringlike enhancing appearance of the lesion is characteristic of tuberculoma, and may play an important role in differentiating intracranial tuberculomas from other ring-enhancing brain lesions.

Adult↗

Effects of activation-defective TBP mutations on transcription initiation in yeast.

Transcription initiation by RNA polymerase II is effected by an ordered series of general factor interactions with core promoter elements (leading to basal activity) and further regulated by gene-specific factors acting from distal elements. Both the general factor TFIID (refs 2,3), including the constituent TBP (TATA-binding polypeptide) and associated factors, and the interacting factor TFIIB (refs 9-11) have been implicated as targets for various activators. Towards an understanding of the basis for activator function, including the multiplicity of TBP interactions, we have now identified mutations in yeast TBP that selectively block activator (GAL4-VP16)-dependent but not basal transcription. We further show an effect of GAL4-VP16 on TFIIB recruitment to early preinitiation complexes, and that recruitment is disrupted by TBP mutations that impair its interactions with VP16 (L114K), TFIIB (L189K) or an unidentified component (K211L). Thus, GAL4-VP16 function seems to involve both direct interactions with TBP and a corresponding induction (or stabilization) of an activation-specific TBP-TFIIB-promoter complex.

Arabidopsis↗

Proline-rich activator CTF1 targets the TFIIB assembly step during transcriptional activation.

Activators can stimulate transcription through direct or indirect interactions with general initiation factors. We show here that the proline-rich activation domain of CTF1 (CCAAT-box-binding transcription factor 1) selectively interacts with TFIIB but not with the TATA-binding protein (TBP), whereas previous studies have shown that the acidic activation domain of viral VP16 interacts directly with both TBP and TFIIB. In addition, consistent with studies of acidic activation domains, we demonstrate that the activation domain of CTF1 facilitates the recruitment (or stabilization) of TFIIB within TBP-DNA complexes during preinitiation complex assembly. CTF1-enhanced TFIIB recruitment was observed in both human and yeast systems. The results indicate that the proline-rich activation domain enhances transcription, at least in part, through direct interactions with TFIIB and, with previous observations, suggest models involving either quantitative or qualitative changes in TFIIB-TFIID-promoter interactions that lead to increased utilization of downstream initiation factors.

Binding Sites↗

Involvement of the basic repeat domain of TATA-binding protein (TBP) in transcription by RNA polymerases I, II, and III.

The TATA-binding protein (TBP) plays a central role in transcription initiation by nuclear RNA polymerases I, II, and III. With knowledge of the three-dimensional structure of TBP, mutational analyses were focused on the highly exposed basic repeat domain in yeast TBP in order to identify amino acid residues which could discriminate transcription functions of different RNA polymerases. One mutation (K156L) was found to specifically abolish transcription by RNA polymerase I and another mutation (K138L) specifically abolished transcription by RNA polymerase III, while each maintained the ability to support in vitro transcription by the other two RNA polymerases. Along with previous studies, these results indicate that the basic repeat domain of TBP is important not only for transcription by RNA polymerase II but also for transcription by RNA polymerases I and III and, further, that the region has distinct sites for interactions which are specific for RNA polymerases I and III.

Amino Acid Sequence↗

Transcriptional activation in yeast by the proline-rich activation domain of human CTF1.

Among eukaryotic transcriptional activators, those with acidic activation domains have been shown to stimulate transcription in organisms ranging from yeast to human. In vivo and in vitro assays have been employed to demonstrate transcriptional enhancement in yeast by the proline-rich activation domain of human CTF1. This result suggests that proline-rich activation domains may, like typical acidic activation domains, functional universally.

CCAAT-Enhancer-Binding Proteins↗

[Differences in the characteristics of hospital stress between medical and surgical patients].

This study explored differences in how medical and surgical patients compare on the degree of hospital stress and their subjective physical status. Subjects were 343 medical and surgical patients in five university hospitals in Seoul and Taegu. They responded to the Hospital Stress Rating Scale and a self-report on physical status. The controlled variables were age, education, number of previous hospitalizations and seriousness of the illness. Medical and surgical patient differences on nine factors of the hospital stress scale and nine areas of physical conditions were reported as follows explored: 1. 1) There was not a statistically significant difference at the .05 level in the total mean score for hospital stress between medical patients and surgical patients. 2) The mean score of the factor lack of information (M=2.308) for medical patients was higher than the mean score (M=2.064) of the surgical patients. 3) The mean scores of the factor of discomfort (M=2.130), loss of independence (M=1.889) for surgical patients were higher than for medical patients. 2. 1) There was a statistically significant difference at the .05 level in the total mean score for physical status between medical patients and surgical patients. 2) The mean scores were lower in subjective physical status for surgical patients (S) than for medical patients (M); stomach condition (S:M=2.8433, M:M=3.0000), self-assistance (S:M=3.0373, M:M=3.4498), movement (S:M=2.6716, M:M=3.2392), interest in your surroundings (S:M=3.0522, M:M=3.2632).(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗