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Articles by J. A Lee
Total Records ( 4 ) for J. A Lee
  J. A Lee , Z. Z Tang and D. L. Black
 

Neuronal depolarization and CaM kinase IV signaling alter the splicing of multiple exons in transcripts for ion channels, neurotransmitter receptors, and other synaptic proteins. These splicing changes are mediated in part by special CaM kinase-responsive RNA elements, within or adjacent to exons that are repressed in the initial phase of chronic depolarization. The splicing of many neuronal transcripts is also regulated by members of the Fox (Feminizing gene on X) protein family, and these Fox targets are also often proteins affecting synaptic activity. We show that Fox-1/Ataxin 2-Binding Protein 1 (A2BP1), a protein implicated in a variety of neurological diseases, can counteract the effects of chronic depolarization on splicing. We find that exon 19 of Fox-1 is itself repressed by depolarization. Fox-1 transcripts missing exon 19 encode a nuclear isoform of Fox-1 that progressively replaces the cytoplasmic Fox-1 isoform as cells are maintained depolarizing media. The resulting increase in nuclear Fox-1 leads to the reactivation of many Fox-1 target exons, including exon 5 of the NMDA receptor 1, that were initially repressed by the high-KCl medium. These results reveal a novel mechanism for the slow modulation of splicing as cells adapt to chronic stimuli: The subcellular localization of a splicing regulator is controlled through its own alternative splicing.

  J. A Lee , M. S Kim , J. S Koh , D. H Kim , J. S Lim , C. B Kong , W. S Song , W. H Cho , S. Y Lee and D. G. Jeon
  Objective

We aimed to understand the biology of osteosarcoma of the flat bone, which is a rare tumor entity.

Methods

Cases with osteosarcoma of the flat bone were compared with those of the extremity in order to evaluate their clinicopathologic characteristics. And the influences of heterogeneous treatment modalities on outcome were analyzed.

Results

Tumors of the flat bone comprised 91 (11.3%) of 806 osteosarcoma cases. Eight cases were secondary osteosarcoma associated with previous radiotherapy. Patients with a flat bone tumor were significantly older and more likely to present with metastases at diagnosis than extremity tumor. The proportions of female sex and chondroblastic subtype were higher among flat bone tumors than among extremity tumors. The 5-year overall survival and event-free survival rates were 35.2 ± 5.4% and 24.7 ± 5.5%, respectively. Although age and histologic response to pre-operative chemotherapy were not related to outcome of flat bone tumors, treatment modality influenced the survival. Patients treated surgically had better outcomes than those treated by another means. Radiation therapy did not appear to be an effective local control measure as surgery.

Conclusions

Treatment outcome of the tumor of the flat bone was worse than extremity tumors. Further studies are needed to identify effective local control measures that can substitute for surgery and to determine the biologic characteristics of osteosarcoma of the flat bone.

  J. A Lee , D. H Kim , J. S Lim , J. S Koh , M. S Kim , C. B Kong , W. S Song , W. H Cho , S. Y Lee and D. G. Jeon
  Objective

Due to the low incidence, treatments for Korean soft tissue Ewing sarcoma patients have been heterogeneous, and reported data are limited. In this study, we retrospectively analyzed soft tissue Ewing cases treated at our institution.

Methods

We analyzed the clinicopathologic characteristics and treatment outcome of soft tissue Ewing sarcoma patients and compared with those of skeletal cases.

Results

Twenty-seven soft tissue Ewing sarcoma cases were evaluated. Patients with soft tissue Ewing sarcoma were older than patients with skeletal tumors (P = 0.03), and tended to have metastasis at diagnosis (P = 0.12). However, sex ratios, pathologies, tumor volumes, and histologic response to preoperative chemotherapy were not different in the two groups. The 5-year overall survival (49.0%) and event-free survival (45.6%) of soft tissue Ewing sarcoma patients were similar to those of skeletal tumor patients (51.8% and 46.0%, respectively). Presence of metastasis at diagnosis and poor histologic response to preoperative chemotherapy were associated with an adverse outcome for both groups. Similar to skeletal tumors, central tumor location, pathology and tumor volume tended to be related to the survival of soft tissue Ewing sarcoma. However, age and the use of a modality other than surgery to achieve local control did not influence the survival of soft tissue Ewing sarcoma patients.

Conclusions

Our data could provide a basis to design a collaborative or multinational study targeting Ewing sarcoma family tumors.

  S. L Edwards , J. A Lee , J. E Bell , J. D Packer , C. S Ahmad , W. N Levine , L. U Bigliani and T. A. Blaine
 

Background: Although there are multiple reports documenting successful outcomes with operative treatment of superior labrum anterior posterior (SLAP) tears, there are few reports on the results of nonoperative treatment.

Hypothesis: Nonoperative treatment of SLAP tears will result in improved outcomes over pretreatment values using validated, patient-derived outcome instruments.

Study Design: Case series; Level of evidence, 4.

Methods: A total of 371 patients with a diagnosis of labral tear at our institution were mailed a questionnaire that included the following validated, patient-derived outcome assessment instruments: Short Form 36 (SF-36), European Quality of Life measure (EuroQol), visual analog pain scale (VAS), American Shoulder and Elbow Surgeons (ASES) score, and simple shoulder test (SST). Sixty-six surveys did not reach the patients because of incorrect addresses, and 50 surveys were returned, for a 16.4% (50 of 305) response rate. Of the patients with a clinically documented SLAP lesion (positive O’Brien test, pain at the bicipital groove, and positive magnetic resonance imaging) and sufficient follow-up data (minimum 1 year), 39 patients who met the criteria returned the survey and 19 had nonoperative treatment. Twenty patients (51%) from the overall surveyed group were considered nonoperative treatment failures and had arthroscopic surgical reconstruction. Nonoperative treatment consisted of nonsteroidal anti-inflammatory drugs and a physical therapy protocol focused on scapular stabilization exercises and posterior capsular stretching. Statistical analysis was performed using the paired t test; values of P < .05 were considered significant.

Results: At an average follow-up of 3.1 years, function improved significantly (ASES function 30.8 to 45.0 [P < .001]; ASES total 58.5 to 84.7 [P = .001], SST 8.3 to 11.0 [P = .02]) in those patients with successful nonoperative treatment. Quality of life also improved after treatment (EuroQol 0.76 to 0.89, P = .009). Pain relief was significant, as VAS pain scores decreased from 4.5 to 2.1 (P = .043). All patients with successful nonoperative treatment returned to sports. Seventy-one percent of all athletes were able to return to preparticipation levels, but only 66% of overhead athletes returned to their sport at the same or higher level.

Conclusion: Using validated, patient-derived outcome instruments, the present study shows that successful nonoperative treatment of superior labral tears results in improved pain relief and functional outcomes compared with pretreatment assessments. Although 20 patients (51%) in this group elected surgery and may be considered nonoperative treatment failures, those patients with successful nonoperative treatment had significant improvements in pain, function, and quality of life. Return to sports was comparable with patients with successful surgical treatment, although return to overhead sports at the same level was difficult to achieve (66%). Based on these findings, a trial of nonoperative treatment may be considered in patients with the diagnosis of isolated superior labral tear. In overhead athletes and in those patients where pain relief and functional improvement is not achieved, surgical treatment should be considered.

 
 
 
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