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P Choi

Publications and source records attributed to P Choi.

At least 19 recordsLinked to original sources
PubMed2005

Linkage analysis of the genetic determinants of T-cell IL-4 secretion, and identification of Flj20274 as a putative candidate gene.

The activation-induced differentiation of naive CD4+ T cells generates functionally divergent type 1 helper T cells (Th1) or type 2 helper T cells (Th2) effector cell populations, characterized by secretion of Interferon (IFN)-gamma or Interleukin (IL)-4, respectively. Inappropriate generation of Th subsets may contribute to immune dysfunction. The decision to generate Th1/Th2 lineages is critically regulated by cytokines, such that IL-12 induces Th1 differentiation, while IL-4 induces Th2 differentiation. Genetic factors influence the pathway of Th differentiation, as displayed by the preferential generation of divergent Th populations by different inbred strains of mice. We employ two complementary genetic techniques to identify genes that regulate the default IL-4 secretion profiles of T cells from BALB/c and B6 mice. We performed a genome-wide linkage analysis of the progeny of a backcross between BALB/c and B6 mice to identify three loci, T-cell secretion of interleukin-4 (Tsi)1-3, on chromosomes 7, 19 and 15, respectively, which regulate in vitro T-cell IL-4 production. We have also employed mRNA representational difference analysis to isolate a gene, Flj20274, which is differentially expressed in T cells that secrete high levels of IL-4. Significantly, Flj20274 was mapped to the point of peak linkage within Tsi1 and is a strong candidate for Tsi1.

Animals↗
PubMed2004

Cellular and molecular characterization of a murine non-union model.

PURPOSE: We have developed a method to study the molecular and cellular events underlying delayed skeletal repair in a model that utilizes distraction osteogenesis. METHODS: The clinical states of delayed union and non-union were reproduced in this murine model by altering distraction parameters such as the inclusion and exclusion of a latency phase and variations in the rate and rhythm of distraction. Radiographic, cellular, and molecular analyses were performed on the distraction tissues. RESULTS: Eliminating the latency period delayed bony union, but did not appreciably alter the extent of platelet endothelial cell adhesion marker (PECAM) immunostaining. Following elimination of a latency phase and a threefold increase in the rate of distraction, there was a further delay in bone regeneration and a higher rate of non-union (60%). Instead of bone, the distraction gap was comprised of adipose or fibrous tissue. Once again, despite the rigorous distraction protocol, we detected equivalent PECAM staining within the distraction gap. In a minority of cases, cartilage and osseous tissues occupied the distraction gap likely by a prolonged process of endochondral ossification. CONCLUSIONS: Here, we have altered the mechanical environment in such a way to reproducibly create delays in skeletal regeneration. These delays in skeletal tissue regeneration appear to develop even in the presence of endothelial cells, which suggests that mechanisms other than a disruption to the vascular network can account for some cases of non-union.

Animals↗
PubMed2003

SEPT5_v2 is a parkin-binding protein.

Mutations in parkin are associated with various inherited forms of Parkinson's disease (PD). Parkin is a ubiquitin ligase enzyme that catalyzes the covalent attachment of ubiquitin moieties onto substrate proteins destined for proteasomal degradation. The substrates of parkin-mediated ubiquitination have yet to be completely identified. Using a yeast two-hybrid screen, we isolated the septin, human SEPT5_v2 (also known as cell division control-related protein 2), as a putative parkin-binding protein. SEPT5_v2 is highly homologous to another septin, SEPT5, which was recently identified as a target for parkin-mediated ubiquitination. SEPT5_v2 binds to parkin at the amino terminus and in the ring finger domains. Several lines of evidence have validated the putative link between parkin and SEPT5_v2. Parkin co-precipitates with SEPT5_v2 from human substantia nigra lysates. Parkin ubiquitinates SEPT5_v2 in vitro, and both SEPT5_v1 and SEPT5_v2 accumulate in brains of patients with ARJP, suggesting that parkin is essential for the normal metabolism of these proteins. These findings suggest that an important relationship exists between parkin and septins.

Aged↗
PubMed2002

Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial.

PURPOSE: Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC. PATIENTS AND METHODS: Patients with Ho's N2 or N3 stage or N1 stage with nodal size > or = 4 cm were randomized to receive cisplatin 40 mg/m(2) weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS). RESULTS: Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P =.10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho's stage T3 (P =.0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P =.016). CONCLUSION: Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages.

Adult↗
PubMed2001

Co-association of parkin and alpha-synuclein.

Parkin and alpha-synuclein are two proteins that are associated with the pathophysiology of Parkinson's disease (PD). Parkin is present in Lewy bodies and axonal spheroids in brains affected by PD, and mutations in parkin cause hereditary forms of Parkinsonism. Alpha-synuclein is a major component of Lewy bodies and is associated with rare cases of PD. We now show that parkin binds to alpha-synuclein, including conditions associated with alpha-synuclein aggregation. Parkin and alpha-synuclein complexes were observed in BE-M17 cells under basal conditions, in BE- M17 cells under oxidative conditions and in brains from control or PD donors. Double staining of PD brains shows parkin and alpha-synuclein co-localize to the same pathological structures (both Lewy bodies and axonal spheroids). These results suggest that parkin interacts with alpha-synuclein and could contribute to the pathophysiology of PD more generally than was previously considered.

Aged↗
PubMed2001

Epidural analgesia reduces postoperative myocardial infarction: a meta-analysis.

UNLABELLED: Postoperative cardiac morbidity and mortality continue to pose considerable risks to surgical patients. Postoperative epidural analgesia is considered to have beneficial effects on cardiac outcomes. The use in high-risk cardiac patients remains controversial. No study has shown that postoperative epidural analgesia decreases postoperative myocardial infarction (PMI) or death. All studies are underpowered to show such a result, and the cost of conducting a large trial is prohibitive. We performed a metaanalysis to determine whether postoperative epidural analgesia continued for more than 24 h after surgery reduces PMI or in-hospital death. The available databases were searched for randomized controlled trials of epidural analgesia that was extended at least 24 h into the postoperative period. The search yielded 17 studies, of which 11 were randomized controlled trials comprising 1173 patients. Metaanalysis was conducted by using the fixed-effects model, calculating both an odds ratio and a rate difference. Postoperative epidural analgesia resulted in better analgesia for the first 24 h after surgery. The rate of PMI was 6.3%, with lower rates in the Epidural group (rate difference, -3.8%; 95% confidence interval [CI] -7.4%, -0.2%; P = 0.049). The frequency of in-hospital death was 3.3%, with no significant difference between Epidural and Nonepidural groups (rate difference, -1.3%; 95% CI, -3.8%, 1.2%, P = 0.091). Subgroup analysis of postoperative thoracic epidural analgesia showed a significant reduction in PMI in the Epidural group (rate difference, -5.3%; 95% CI, -9.9%, -0.7%; P = 0.04). IMPLICATIONS: Postoperative epidural analgesia, especially thoracic epidural analgesia, continued for more than 24 h reduces postoperative myocardial infarctions.

Analgesia, Epidural↗
PubMed2000

Parkin is metabolized by the ubiquitin/proteosome system.

Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Immunostaining of substantia nigra sections from sporadic Parkinson's disease (PD) cases shows that Parkin accumulates in axonal spheroids and in some Lewy bodies. Because ubiquitin is a major component of Lewy bodies and axonal spheroids, we investigated whether Parkin is metabolized via the ubiquitin/proteosomal pathway. Treatment of BE-M17 neuroblastoma cells with the proteosomal inhibitor, MG132, produced a band corresponding to di-ubiquitinated Parkin that was apparent by immunoblot using two different anti-Parkin antibodies. This higher mol. wt band also co-immunoprecipitated with Parkin. These data suggest that Parkin plays a role in the pathophysiology of sporadic PD, and that Parkin is a substrate for ubiquitination that is degraded by the proteosomal complex.

Aged↗
PubMed2000

Ionization waves in electron-beam-assisted, shielded capillary discharge

A theory of propagation of cathode-directed ionization waves during the early stages of an electrical breakdown in a shielded, low-pressure capillary is developed. The discharge process occurs due to the ionization of the low-density gas in the capillary by an electron beam that is emanating from a hollow cathode. Due to the strong electric field in the capillary the electrons are in the fast acceleration regime. Consequently, the full momentum equation for the electrons is employed, rather than the electron drift velocity approach. The smallness of the ratio of the capillary radius to the characteristic length of the electric potential variation in the axial direction allows the construction of a quasi-one-dimensional model. The latter retains the important two-dimensional nature of the electron flow as well as the electrodynamic boundary conditions at the capillary wall and the conducting shield and results in a set of one-dimensional, time-dependent partial differential equations for the on-axis distributions of the physical quantities. It is shown that those equations admit self-similar solutions that represent ionization waves propagating with constant velocities. The resulting set of ordinary differential equations is solved numerically for various initial conditions representing a nonperturbed steady state ahead of the ionization front and the resulting features of the ionization waves are investigated and discussed. The obtained solutions describe both ionization growth and virtual anode propagation and represent fast ionization waves in plasma waveguides, for which the maximum value of the mean electron velocity is much higher than the wave velocity. The space-charge distribution associated with the ionization waves is found in the form of plasma oscillations with a continuously increasing frequency and a solitary envelope. The calculated wave velocity increases with the gas pressure and this tendency is in agreement with corresponding experimental observations.

Journal Article↗
PubMed1999

alpha-Synuclein shares physical and functional homology with 14-3-3 proteins.

alpha-Synuclein has been implicated in the pathophysiology of many neurodegenerative diseases, including Parkinson's disease (PD) and Alzheimer's disease. Mutations in alpha-synuclein cause some cases of familial PD (Polymeropoulos et al., 1997; Kruger et al., 1998). In addition, many neurodegenerative diseases show accumulation of alpha-synuclein in dystrophic neurites and in Lewy bodies (Spillantini et al., 1998). Here, we show that alpha-synuclein shares physical and functional homology with 14-3-3 proteins, which are a family of ubiquitous cytoplasmic chaperones. Regions of alpha-synuclein and 14-3-3 proteins share over 40% homology. In addition, alpha-synuclein binds to 14-3-3 proteins, as well as some proteins known to associate with 14-3-3, including protein kinase C, BAD, and extracellular regulated kinase, but not Raf-1. We also show that overexpression of alpha-synuclein inhibits protein kinase C activity. The association of alpha-synuclein with BAD and inhibition of protein kinase C suggests that increased expression of alpha-synuclein could be harmful. Consistent with this hypothesis, we observed that overexpression of wild-type alpha-synuclein is toxic, and overexpression of alpha-synuclein containing the A53T or A30P mutations exhibits even greater toxicity. The activity and binding profile of alpha-synuclein suggests that it might act as a protein chaperone and that accumulation of alpha-synuclein could contribute to cell death in neurodegenerative diseases.

14-3-3 Proteins↗
PubMed1999

Experience with breast biopsies using the Advanced Breast Biopsy Instrumentation system.

OBJECTIVE: A retrospective review of our experience with advanced breast biopsy instrumentation (ABBI) was undertaken to evaluate its efficacy for excisional breast biopsy of lesions detected on mammography. To our knowledge, experience with ABBI has not been previously reported in the radiology literature. MATERIALS AND METHODS: Biopsies using the ABBI system and an adapted dedicated table were performed in 53 patients who had 54 mammographically evident lesions. Samples were obtained with cannulas ranging in size between 5 and 20 mm. Indications for biopsy were calcifications (n = 22) and masses (n = 31). RESULTS: Forty-five specimens (44 patients) had benign results at pathology: 15 specimens were diagnosed as fibroadenoma, 15 as cystic breast disease, and four as reactive lymph nodes; the remaining 11 specimens had benign diagnoses of adenosis, fibrosis, and hyperplasia. The average specimen size was 4.8 cm in greatest longitudinal dimension. One patient had a nondiagnostic biopsy for calcifications later found to be dermal. Seven patients were diagnosed as having breast cancer; in six of these, the tumor involved the margins of the specimen. One patient had marked atypia that required reexcision for the diagnosis of intraductal carcinoma to be made. CONCLUSION: The ABBI procedure is a more invasive and less readily available procedure than core needle biopsy for sampling of benign breast lesions. In seven cases of malignancy diagnosed at breast biopsy, the ABBI technique completely excised only a single lesion. In our experience, the ABBI procedure offered no advantages over core needle biopsy for either benign or malignant lesions.

Biopsy, Needle↗
PubMed1998

Staging and IgA VCA titre in patients with nasopharyngeal carcinoma: changes over a 12-year period.

The distributions of 2093 patients with nasopharyngeal carcinoma (NPC), by stage, over a 12-year-period did not show any evidence of a shift towards early stages despite growing awareness of this prevalent malignancy. The IgA VCA titre was determined for 1880 of these patients. The median titre increased from 40 in stage I to 80 in stages II, III, and IV, before rising to 160 in stage V. The percentage of patients with a titre > or = 320 increased steadily with advancing stages. Within the same disease stage, the percentage of patients having a particular titre value and the median titre varied considerably from year to year. Better education of the general population and a better serological marker for screening are needed for the early detection of NPC.

Antibodies, Neoplasm↗
PubMed1998

Characterization of glucose-specific catabolite repression-resistant mutants of Bacillus subtilis: identification of a novel hexose:H+ symporter.

Insertional mutagenesis was conducted on Bacillus subtilis cells to screen for mutants resistant to catabolite repression. Three classes of mutants that were resistant to glucose-promoted but not mannitol-promoted catabolite repression were identified. Cloning and sequencing of the mutated genes revealed that the mutations occurred in the structural genes for (i) enzyme II of the phosphoenolpyruvate-glucose phosphotransferase (PtsG), (ii) antiterminator GlcT, which controls PtsG synthesis, and (iii) a previously uncharacterized carrier of the major facilitator superfamily, which we have designated GlcP. The last protein exhibits greatest sequence similarity to the fucose:H+ symporter of Escherichia coli and the glucose/galactose:H+ symporter of Brucella abortus. In a wild-type B. subtilis genetic background, the glcP::Tn10 mutation (i) partially but specifically relieved glucose- and sucrose-promoted catabolite repression, (ii) reduced the growth rate in minimal glucose medium, and (iii) reduced rates of [14C]glucose and [14C]methyl alpha-glucoside uptake. In a delta pts genetic background no phenotype was observed, suggesting that expression of the glcP gene required a functional phosphotransferase system. When overproduced in a delta pts mutant of E. coli, GlcP could be shown to specifically transport glucose, mannose, 2-deoxyglucose and methyl alpha-glucoside with low micromolar affinities. Accumulation of the nonmetabolizable glucose analogs was demonstrated, and inhibitor studies suggested a dependency on the proton motive force. We conclude that B. subtilis possesses at least two distinct routes of glucose entry, both of which contribute to the phenomenon of catabolite repression.

Amino Acid Sequence↗
PubMed1998

Nasopharyngeal carcinoma---time lapse before diagnosis and treatment.

This is a descriptive study of 168 patients with nasopharyngeal carcinoma who were referred to public oncology departments for primary treatment between July and September 1996. The mean duration from the onset of the symptoms to histological diagnosis was 5.0 months; the duration ranged from 6.1 months (for patients presenting with nasal symptoms) to 1.8 months (for those with cranial nerve dysfunction). The mean period between the onset of symptoms and the seeking of medical advice was 2.9months. For 54% of the patients, there was a further delay of up to 2.4 months between the initial medical consultation and referral to the appropriate specialist. The majority (84%) of patients attended public institutions for histological confirmation. The mean total time taken from the onset of symptoms to the commencement of radiotherapy was 6.5 months (range, 1.3-74.0 months)---45% of the delay was attributed to the patient, 20% to initial consultations, 14% to diagnostic arrangement, and 21% to preparation for radiotherapy. Concerted efforts are needed to minimise further the time between the onset of symptoms and treatment. A substantial reduction in this delay can be achieved if both public and primary care doctors were made more aware of the significance of relevant symptoms.

Journal Article↗
PubMed1997

Concurrent subarachnoid haemorrhage and myocardial injury.

PURPOSE: Subarachnoid haemorrhage is frequently associated with myocardial injury and dysfunction. This report describes such a case, reviews the understanding of this phenomenon, and discusses the implications for timing of surgical clipping of intracranial aneurysm in patients with concurrent myocardial damage. CLINICAL FEATURES: A 64-yr-old women presented with syncope and congestive heart failure. A diagnosis of subarachnoid haemorrhage was made three days following the initial diagnosis of myocardial infarction. The patient presented for clipping of an intracranial aneurysm on day 36, after her cardiac status had stabilized. No new myocardial ischaemic events occurred, either intra-operatively or post-operatively. Ultimate neurological recovery was poor. CONCLUSIONS: This case report demonstrates four important aspects of the clinical course of patients with concurrent subarachnoid haemorrhage and myocardial damage: 1) On presentation, cardiac features may predominate, and delay diagnosis and treatment of the underlying subarachnoid haemorrhage. 2) Left ventricular dysfunction, although dramatic, is usually transient. 3) There is confusion regarding the appropriate cardiac risk assessment and management in such patients when presenting for surgery. 4) Long-term morbidity is most often related to neurological, not medical, complications.

Electrocardiography↗
PubMed1996

Significant prognosticators after primary radiotherapy in 903 nondisseminated nasopharyngeal carcinoma evaluated by computer tomography.

PURPOSE: To evaluate the significant prognosticators in nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: From 1984 to 1989, 903 treatment-naive nondisseminated (MO) NPC were given primary radical radiotherapy to 60-62.5 Gy in 6 weeks. All patients had computed tomographic (CT) and endoscopic evaluation of the primary tumor. Potentially significant parameters (the patient's age and sex, the anatomical structures infiltrated by the primary lesion, the cervical nodal characteristics, the tumor histological subtypes, and various treatment variables were analyzed by both monovariate and multivariate methods for each of the five clinical endpoints: actuarial survival, disease-free survival, free from distant metastasis, free from local failure, and free from regional failure. RESULTS: The significant prognosticators predicting for an increased risk of distant metastases and poorer survival included male sex, skull base and cranial nerve(s) involvement, advanced Ho's N level, and presence of fixed or partially fixed nodes or nodes contralateral to the side of the bulk of the nasopharyngeal primary. Advanced patient age led to significantly worse survival and poorer local tumor control. Local and regional failures were both increased by tumor infiltrating the skull base and/or the cranial nerves. In addition, regional failure was increased significantly by advancing Ho's N level. Parapharyngeal tumor involvement was the strongest independent prognosticator that determined distant metastasis and survival rates in the absence of the overriding prognosticators of skull base infiltration, cranial nerve(s) palsy, and cervical nodal metastasis. CONCLUSIONS: The significant prognosticators are delineated after the advent of CT and these should form the foundation of the modern stage classification for NPC.

Adult↗