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T Choi

Publications and source records attributed to T Choi.

At least 19 recordsLinked to original sources
PubMed2001

A novel class of highly potent, selective, and non-peptidic inhibitor of Ras farnesyltransferase (FTase).

Design, synthesis and structure-activity relationship of a class of aryl pyrroles as farnesyltransferase inhibitors are described. In vitro and in vivo evaluation of a panel of these inhibitors led to identification of 2 (LB42908) as a highly potent (IC(50)=0.9 nM against H-Ras and 2.4 nM against K-Ras) antitumor agent that is currently undergoing preclinical studies.

Alkyl and Aryl Transferases↗
PubMed2000

The DNA replication-related element (DRE)-DRE-binding factor (DREF) system may be involved in the expression of the Drosophila melanogaster TBP gene.

The TATA box binding protein (TBP) is a general transcription factor required for initiation by all three eukaryotic RNA polymerases. Previously, we found that the promoter region of the Drosophila melanogaster TBP gene contains three sequences similar to the DNA replication-related element (DRE) (5'-TATCGATA). In the present study, we found that the DRE-like sequences are also present in the promoter of the Drosophila virilis TBP gene, suggesting a role for these sequences in TBP expression. Band mobility shift assays revealed that oligonucleotides containing sequences similar to the DRE of D. melanogaster TBP gene promoter form specific complexes with a factor in a Kc cell nuclear extract and with recombinant DRE-binding factor (DREF). Furthermore, these complexes were either supershifted or diminished by monoclonal antibodies to DREF. Transient luciferase assays demonstrated that induction of mutations in two DRE-related sequences at positions -223 and -63 resulted in an extensive reduction of promoter activity. Thus, the DRE-DREF system appears to be involved in the expression of the D. melanogaster TBP gene.

Animals↗
PubMed2000

Total pelvic exenteration and reconstruction for locally invasive recurrent sarcoma of the perineum.

Extensive primary tumors and locally recurrent tumors of the pelvis or perineum are difficult to manage. We describe the techniques necessary to perform total pelvic exenteration with en bloc resection of the perineum and genitalia for treatment of recurrent sarcoma of the perineum. Wide excision of the sarcoma with negative margins can be achieved by resecting the inferior portion of the pubic symphysis. An absorbable mesh sling may be used to suspend the small bowel above the pelvis, facilitating postoperative radiation. A catheterizable continent urinary reservoir avoids the necessity of two stomas and improves quality of life. Adequate tissue coverage can be attained by myocutaneous gracilis flaps that promote wound healing.

Adult↗
PubMed1999

Urinary free beta hCG, beta core fragment and total oestriol as markers of Down syndrome in the second trimester of pregnancy.

In a study of 69 random urine samples from cases of Down syndrome and 405 samples from unaffected pregnancies, we have assessed the value of various candidate markers that have been proposed as tools for screening for Down syndrome. We found that the marker urine free beta hCG in Down syndrome had a median MoM of 3.53 (95 per cent confidence interval 2.48-4.68) and at a 5 per cent cut-off would have identified 49 per cent (34/69) of cases. Urine beta core had a median MoM of 4.95 (3.87-8.62) and at a 5 per cent cut-off would have identified 39 per cent (27/69) of cases. Total oestriol had a median MoM of 0.65 (0.55-0.80) and at a 5 per cent cut-off would have identified 35 per cent (24/69) of cases. In conjunction with maternal age, the modelled detection rate increased to 55.8 per cent for free beta hCG, 49.8 per cent for beta core and 48.8 per cent for total oestriol. In combination free beta hCG, total oestriol and maternal age would have detected 68 per cent of cases for a 5 per cent false-positive rate. Using analyte ratios to obviate the need to correct for urine dilution in our study (rather than correcting to a fixed creatinine concentration) was not shown to be as effective as correcting using urine creatinine. Urine markers on the whole are unlikely to be of practical screening value considering the 85 per cent to 90 per cent detection rates achievable in the first trimester using a combination of ultrasound and maternal serum biochemistry.

Adult↗
PubMed1998

Extended outpatient rehabilitation: its influence on symptom frequency, fatigue, and functional status for persons with progressive multiple sclerosis.

OBJECTIVE: To determine the influence of an extended outpatient rehabilitation program on symptom frequency, fatigue, and functional status for persons with multiple sclerosis (MS). DESIGN: Nonequivalent pretest/posttest control-group design, with posttest 1 year after initial assessment. Multiple regression analysis and analysis of covariance were used to control for symptom severity at the initial assessment and comorbid factors including depression, cognitive function, and social interaction. Effect sizes (ES) provided a descriptive measure of the change in outcomes. SETTING: Outpatient multidisciplinary rehabilitation clinic. PATIENTS: Forty-six patients with definite chronic progressive MS; 20 received treatment and 26 were in a nontreatment comparison group ("waiting list"). INTERVENTION: Rehabilitation services for 5 hours, 1 day per week, over 1 year. MAIN OUTCOME MEASURES: The MS-Related Symptom Checklist composite score, fatigue frequency, and selected items from the Rehabilitation Institute of Chicago Functional Assessment Scale. RESULTS: Receiving treatment was a significant predictor of reduced symptom frequency (partial r2 = .26) at the 1-year follow-up. The ES adjusted for baseline values indicated substantial reductions in symptom frequency for the treatment group (EStreatment = .27 vs ESwaitlist = -.32). Fatigue was significantly reduced at the time of follow-up for the treatment group compared with the waiting list group (EStreatment = .46 vs ESwaitlist = -.20). There were no statistically significant differences among groups regarding functional status, but there appeared to be less loss of functional status in the treatment group compared with the waiting list group (EStreatment = -.07 vs ESwaitlist = -.70). CONCLUSIONS: An extended outpatient rehabilitation program for persons with definite progressive MS appears to effectively reduce fatigue and the severity of other symptoms associated with MS.

Adult↗
PubMed1997

CENP-E is an essential kinetochore motor in maturing oocytes and is masked during mos-dependent, cell cycle arrest at metaphase II.

CENP-E, a kinesin-like protein that is known to associate with kinetochores during all phases of mitotic chromosome movement, is shown here to be a component of meiotic kinetochores as well. CENP-E is detected at kinetochores during metaphase I in both mice and frogs, and, as in mitosis, is relocalized to the midbody during telophase. CENP-E function is essential for meiosis I because injection of an antibody to CENP-E into mouse oocytes in prophase completely prevented progression of those oocytes past metaphase I. Beyond this, CENP-E is modified or masked during the natural, Mos-dependent, cell cycle arrest that occurs at metaphase II, although it is readily detectable at the kinetochores in metaphase II oocytes derived from mos-deficient (MOS-/-) mice that fail to arrest at metaphase II. This must reflect a masking of some CENP-E epitopes, not the absence of CENP-E, in meiosis II because a different polyclonal antibody raised to the tail of CENP-E detects CENP-E at kinetochores of metaphase II-arrested eggs and because CENP-E reappears in telophase of mouse oocytes activated in the absence of protein synthesis.

Animals↗
PubMed1997

Health-related quality of life for patients with progressive multiple sclerosis: influence of rehabilitation.

BACKGROUND AND PURPOSE: The health-related quality of life of patients with multiple sclerosis (MS) is an important aspect of care outcome. The purpose of this study was to compare health-related quality of life between patients who received weekly comprehensive outpatient rehabilitation for 1 year and a group that did not receive rehabilitation. SUBJECTS: Twelve patients receiving outpatient care for chronic progressive MS (mean age = 44.5 years, SD = 11.6) were compared with 19 similar patients (mean age = 49.2 years, SD = 9.2) on a waiting list who were not receiving outpatient care. METHODS: A pretest-posttest longitudinal design was used to descriptively compare outcome measures. Multivariate regression analyses were used to determine which variables, controlled for baseline health status and other relevant patient characteristics, were related to the best outcomes at the time of the 1-year follow-up. RESULTS: The treatment group showed improvements in six health status measures on the Rand 36-Item Health Survey 1.0 (SF-36) that were not improved in the wait-listed group. Outpatient treatment was the sole predictor of positive outcome for energy/fatigue (partial R2 = .43) and change in general health (partial R2 = .19). In addition, the treatment group was associated with a positive outcome (together with other independent variables) in the domains of social function and social support. CONCLUSION AND DISCUSSION: Patients with chronic progressive forms of MS appear to derive benefits from an ongoing comprehensive outpatient rehabilitation program. [Di Fabio RP, Choi T, Soderberg J, Hansen CR. Health-related quality of life for patients with progressive multiple sclerosis: influence of rehabilitation.

Adult↗
PubMed1996

The Mos/mitogen-activated protein kinase (MAPK) pathway regulates the size and degradation of the first polar body in maturing mouse oocytes.

Mos is an upstream activator of mitogen-activated protein kinase (MAPK) and, in mouse oocytes, is responsible for metaphase II arrest. This activity has been likened to its function in Xenopus oocytes as a component of cytostatic factor. Thus, Mos-deficient female mice (MOS-/-) are less fertile and oocytes derived from these animals fail to arrest at metaphase II and undergo parthenogenetic activation [Colledge, W. H., Carlton, M. B. L., Udy, C. B. & Evans, M. J. (1994) Nature (London) 370, 65-68 and Hashimoto, N., Watanabe, N., Furuta. Y., Tamemoto, B., Sagata, N., Yokoyama, M., Okazaki, K., Nagayoshi, M., Takeda, N., Ikawa, Y. & Aizawa, S. (1994) Nature (London) 370, 68-71]. Here we show that maturing MOS-/- oocytes fail to activate MAPK throughout meiosis, while p34cdc2 kinase activity is normal until late in metaphase II when it decreases prematurely. Phenotypically, the first meiotic division of MOS-/- oocytes frequently resembles mitotic cleavage or produces an abnormally large polar body. In these oocytes, the spindle shape is altered and the spindle fails to translocate to the cortex, leading to the establishment of an altered cleavage plane. Moreover, the first polar body persists instead of degrading and sometimes undergoes an additional cleavage, thereby providing conditions for parthenogenesis. These studies identify meiotic spindle formation and programmed degradation of the first polar body as new and important roles for the Mos/MAPK pathway.

Animals↗
PubMed1996

Mos/mitogen-activated protein kinase can induce early meiotic phenotypes in the absence of maturation-promoting factor: a novel system for analyzing spindle formation during meiosis I.

Mitogen-activated protein kinase (MAPK) is selectively activated by injecting either mos or MAPK kinase (mek) RNA into immature mouse oocytes maintained in the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). IBMX arrests oocyte maturation, but Mos (or MEK) overexpression overrides this block. Under these conditions, meiosis I is significantly prolonged, and MAPK becomes fully activated in the absence of p34cdc2 kinase or maturation-promoting factor. In these oocytes, large openings form in the germinal vesicle adjacent to condensing chromatin, and microtubule arrays, which stain for both MAPK and centrosomal proteins, nucleate from these regions. Maturation-promoting factor activation occurs later, concomitant with germinal vesicle breakdown, the contraction of the microtubule arrays into a precursor of the spindle, and the redistribution of the centrosomal proteins into the newly forming spindle poles. These studies define important new functions for the Mos/MAPK cascade in mouse oocyte maturation and, under these conditions, reveal novel detail of the early stages of oocyte meiosis I.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Abnormal centrosome amplification in the absence of p53.

The centrosome plays a vital role in mitotic fidelity, ensuring establishment of bipolar spindles and balanced chromosome segregation. Centrosome duplication occurs only once during the cell cycle and is therefore highly regulated. Here, it is shown that in mouse embryonic fibroblasts (MEFs) lacking the p53 tumor suppressor protein, multiple copies of functionally competent centrosomes are generated during a single cell cycle. In contrast, MEFs prepared from normal mice or mice deficient in the retinoblastoma tumor suppressor gene product do not display these abnormalities. The abnormally amplified centrosomes profoundly affect mitotic fidelity, resulting in unequal segregation of chromosomes. These observations implicate p53 in the regulation of centrosome duplication and suggest one possible mechanism by which the loss of p53 may cause genetic instability.

Animals↗
PubMed1996

Notational analysis on game strategy used by the world's top male squash players in international competition.

The purpose of this study was to provide a profile of the competition strategy used by the world's top squash players at the international level and provide recommendations for other players to improve their playing strategy. A total of 10 matches including three in round one, the four quarter finals, the two semi-finals, and the final of the 1993 Hong Kong Squash Open were filmed using a 3-CDD video camera. The tournament was played under the North American scoring system. Notational analysis which is based on frame by frame video analysis was used to categorize a player's motion. The frequency of each stroke, and the success or failure rate of each stroke were recorded. Shots were classified as "effective", "ineffective", "winning" and "losing" shots and the analysis demonstrated that 70.28% were "effective", 19.86% were "ineffective", 5.37% were "winning" and 4.48% were "losing" shots. The mean number of shots per game was 252.09. The order of priority using different kinds of strokes in matches were as follows: drive (length) (60.79%), drop (17.91%), volley (11.79%), boast (4.80%), and lob (4.72%). The results of this study show that the "pressure and attack game" was the most important strategy for the world's top squash players in producing winning performances. Also identified are the strokes and the strategies which should be practiced to improve performance. This method of notational analysis can be utilized to evaluate the strengths and weaknesses of players at all levels of competition.

Competitive Behavior↗
PubMed1993

Identification of ras targets using a genetic approach.

The Sevenless receptor tyrosine kinase is required for the development of the R7 photoreceptor cell in the Drosophila eye. Several components of the Sevenless signal transduction pathway have been identified in genetic screens for enhancers/suppressors of the sevenless phenotype. These studies suggest that activation of Sevenless leads to stimulation of Ras1 activity, whereas Gap1 appears to act as a negative regulator of the pathway. Inactivation of the Gap1 locus causes transformation of non-neuronal cone cells into supernumerary R7 cells. This same mutant phenotype is observed when activated Ras1 is expressed under the control of the sevenless promoter. While studies in other organisms have demonstrated a role for ras gene products in signal transduction, the effectors of Ras activity have not yet been identified. We are carrying out genetic screens for enhancers and suppressors of the Gap1 and activated Ras1 phenotypes in the hope of identifying genes encoding some of these effectors. We are conducting chemical mutagenesis screens and have also screened existing collections of P element lines. A molecular characterization of the most promising mutations is in progress.

Animals↗
PubMed1993

Caregivers of frail elderly and medically fragile children: perceptions of ability to continue to provide home health care.

The purposes of this study were to compare the characteristics and support systems of caregivers of frail elderly and medically fragile children and to determine what factors discriminated between caregivers who could (and could not) continue to provide home health care. Caregivers of children were significantly more likely (chi 2 = 52.30)2), p = < .0000) to report that they were managing OK than caregivers of frail elderly. They also reported receiving more support and assistance from formal and informal sources, although in general, less than 30% of the caregivers received any help. Five variables (Mental impairment of the elder, poor physical and mental health of the caregiver, high monthly caregiving-related expenses, and use of paid in-home assistance) explained 35% of the variance between caregivers of frail elderly who were managing OK and those who were unable to continue to manage. Six variables (physical and mental impairment of the child, physical health of the caregiver, feeling like there were no alternative providers, time demand and lack of assistance from others) explained 26.57% of the variance between caregivers of children who were managing OK and those who were unable to continue to manage. The findings suggest that a strong objective stressor, combined with a lack of personal and social resources are associated with caregivers' perceptions that they cannot continue to manage home health care.

Adult↗
PubMed1992

A deficiency in the mechanism for p34cdc2 protein kinase activation in mouse embryos arrested at 2-cell stage.

Mouse embryos of the ddY strain fertilized in vitro undergo the first cleavage to the 2-cell stage but not the second cleavage even 45 hr after insemination (2-cell block). We examined the phosphorylation state of p34cdc2 and histone H1 kinase activity in mouse 2-cell embryos to investigate the relationship of p34cdc2 with 2-cell block. In the first mitotic cell cycle, the amount of phosphorylated forms of p34cdc2, which were detected as the bands of retarded mobility on SDS-PAGE followed by immunoblotting with anti-p34cdc2 antibody, increased during interphase and abruptly decreased at M phase. Concomitant with this dephosphorylation, histone H1 kinase activity was increased. After the embryos cleaved to the 2-cell stage, the amounts of phosphorylated forms of p34cdc2 increased up to 33 hr after insemination. However, the activation of histone H1 kinase did not occur and the states of phosphorylation of p34cdc2 did not show any significant changes until 45 hr. In contrast, 2-cell embryos of B6C3F1 mice, which do not show a 2-cell block and develop normally to blastocysts in vitro, exhibit the dephosphorylation of p34cdc2 and an increase in histone H1 kinase activity between 31 and 45 hr after insemination. When the ddY mouse embryos arrested at the 2-cell stage were treated with okadaic acid, an inhibitor of protein phosphatases 1 and 2A, the dephosphorylation of p34cdc2 occurred and histone H1 kinase activity increased. The chromosomes of these embryos stained with 4',6'-diamidino-2-phenylindole revealed the initiation of condensation. These results suggest that 2-cell-blocked embryos contain enough p34cdc2 to induce mitotic events but the protein remains in a latent form.

Animals↗
PubMed1991

A generic intron increases gene expression in transgenic mice.

To investigate the role of splicing in the regulation of gene expression, we have generated transgenic mice carrying the human histone H4 promoter linked to the bacterial gene for chloramphenicol acetyltransferase (CAT), with or without a heterologous intron in the transcription unit. We found that CAT activity is 5- to 300-fold higher when the transgene incorporates a hybrid intron than with an analogous transgene precisely deleted for the intervening sequences. This hybrid intron, consisting of an adenovirus splice donor and an immunoglobulin G splice acceptor, stimulated expression in a broad range of tissues in the animal. Although the presence of the hybrid intron increased the frequency of transgenics with significant CAT activity, it did not affect the integration site-dependent variation commonly seen in transgene expression. To determine whether the enhancement is a general outcome of splicing or is dependent on the particular intron, we also produced equivalent transgenics carrying the widely used simian virus 40 small-t intron. We found that the hybrid intron is significantly more effective in elevating transgene expression. Our results suggest that inclusion of the generic intron in cDNA constructs may be valuable in achieving high levels of expression in transgenic mice.

Animals↗
PubMed1991

Activation of p34cdc2 protein kinase activity in meiotic and mitotic cell cycles in mouse oocytes and embryos.

p34cdc2 protein kinase is a universal regulator of M-phase in eukaryotic cell cycle. To investigate the regulation of meiotic and mitotic cell cycle in mammals, we examined the changes in phosphorylation states of p34cdc2 and its histone H1 kinase activity in mouse oocytes and embryos. We showed that p34cdc2 has three different migrating bands (referred to as upper, middle and lower bands) on SDS-PAGE followed by immunoblotting with anti-PSTAIR antibody, and that the upper and middle bands are phosphorylated forms since these two bands shifted to the lower one by alkaline phosphatase treatment. In meiotic cell cycle, only germinal vesicle (GV) stage oocytes had the three forms. The phosphorylated forms decreased gradually in oocytes up to 2 h after isolation from follicles, and thereafter the phosphorylation states did not change significantly until metaphase II. However, the histone H1 kinase activity oscillated, being activated at the first and second metaphase in meiosis and inactivated at the time of the first polar body extrusion. These results suggest that changes in phosphorylation states of p34cdc2 triggered its activation at the first metaphase, but not inactivation and reactivation at the first and second metaphase, respectively. In mitotic cell cycle, phosphorylated forms appeared at 4 h after insemination, increased greatly just before metaphase, and were dephosphorylated in metaphase. Histone H1 kinase activity was high only at metaphase. This kinase activation is probably triggered by dephosphorylation of p34cdc2.

Animals↗