Biomedical subjects

H A Chansky

Publications and source records attributed to H A Chansky.

7 recordsLinked to original sources

PubMed2001

Oncogenic TLS/ERG and EWS/Fli-1 fusion proteins inhibit RNA splicing mediated by YB-1 protein.

The translocation liposarcoma protein TLS has recently been shown to function as an adapter molecule coupling gene transcription to RNA splicing. Here we demonstrate that YB-1, a protein known to play important roles in transcription and translation, interacts with the COOH-terminal domains of TLS and the structurally related Ewing's sarcoma protein EWS. Through this interaction, YB-1 is recruited to RNA polymerase II and promotes splicing of E1A pre-mRNA to the 13S isoform. This splicing function of YB-1 is inhibited by exogenous TLS/ERG or EWS/Fli-1 fusion proteins, which bind to RNA polymerase II but fail to recruit the YB-1 protein. In Ewing's sarcoma cells that express endogenous EWS/Fli-1, this linkage between YB-1 and RNA Pol II via EWS (or TLS) was found to be defective. Together, these results suggest that TLS and EWS fusion proteins may contribute to malignant transformation through disruption of RNA splicing mediated by TLS- and EWS-binding proteins such as YB-1.

3T3 Cells↗

PubMed2000

EWS.Fli-1 fusion protein interacts with hyperphosphorylated RNA polymerase II and interferes with serine-arginine protein-mediated RNA splicing.

Ewing's sarcoma displays a characteristic chromosomal translocation that results in fusion of the N-terminal domain of the Ewing's sarcoma protein (EWS) to the C-terminal DNA-binding domain of the ETS family transcription factor Fli-1 (Friend leukemia integration-1). EWS possesses structural motifs suggesting a role in transactivation as well as RNA binding. We demonstrate that wild-type EWS protein functions as an adapter molecule coupling transcription to RNA splicing by binding to hyperphosphorylated RNA polymerase II through the N-terminal domain of EWS and recruiting serine-arginine (SR) splicing factors through the C-terminal domain of EWS. The oncogenic EWS.Fli-1 fusion protein retains the ability to bind to hyperphosphorylated RNA polymerase II but lacks the ability to recruit SR proteins because of replacement of the C-terminal domain of EWS by Fli-1. In an in vivo splicing assay, the EWS.Fli-1 fusion protein inhibits SR protein-mediated E1A pre-mRNA splicing in a dominant-negative manner. These results indicate that EWS.Fli-1 interferes with the normal function of EWS and implicate uncoupling of gene transcription from RNA splicing in the pathogenesis of Ewing's sarcoma.

Animals↗

PubMed2000

Irreducible posterolateral dislocation of the knee.

Traumatic knee dislocations are relatively rare, often associated with neurovascular injury, and almost always amenable to closed reduction. However, over the years, several authors have recognized that the rare knee dislocation not reducible by closed manipulation usually involves posterolateral dislocation of the tibia and button-holing of the medial femoral condyle through the medial retinaculum. These cases present with a dimple sign, a characteristic invagination of tissues at the medial joint line. Open reduction entails extraction of the soft-tissue collar that becomes incarcerated in the trochlea and intercondylar notch. We present an interesting case of irreducible posterolateral knee dislocation and review many of the salient points associated with this entity. Additionally, we include intraoperative video footage available on the Journal Web site to promote a better appreciation of the dramatic visual presentation and physical examination of this unusual injury.

Follow-Up Studies↗

PubMed1999

Evidence for a polyclonal etiology of palmar fibromatosis.

X chromosome inactivation patterns at the androgen receptor locus were evaluated to determine clonality in microdissected lesional tissue and in leukocytes from 2 women with Dupuytren's disease. The tissue from both patients generated a polyclonal pattern of X chromosome inactivation of the human androgen receptor gene. This finding supports a polyclonal reactive process as the underlying etiology for palmar fibromatosis.

Dosage Compensation, Genetic↗

PubMed1996

Pediatric soft-tissue sarcomas.

Pediatric soft-tissue sarcomas represent a relatively common problem in pediatric oncology. The evaluation of these lesions has contributed significantly to the understanding of the molecular basis of sarcomas, and the adjuvant treatment of these tumors has resulted in improved local control and significant improvements in long-term survival. The essence of successful treatment involves preoperative imaging, followed by needle biopsy, preoperative neoadjuvant chemotherapy, and well-documented surgical resection. Indications for radiation therapy and the adequacy of surgical margins remain areas of further investigation. The identification and treatment of well-defined histologic and molecular subtypes will allow further improvements in treatment decisions and clinical results.

Child↗

PubMed1994

Effect of sterilization and storage treatments on screw pullout strength in human allograft bone.

Many conflicting studies have been performed evaluating the effects of sterilization and storage treatments on the mechanical properties of allograft bone. In the current study, four right and left matched, sterile, deep-frozen, tibial pairs from human donors with an average age of 32 years were tested. One tibia from each pair served as a matched control for the opposite side. Each tibia was cut into four equal segments. One segment of each tibia underwent no treatment; the other three underwent one of the following treatments: irradiation, freeze drying, or ethylene oxide (ETO). Screw pullout tests were performed using four 3.5-mm cortical screws per segment. Sixteen screw pullout tests were performed for each allograft treatment. The freeze-dried specimens required significantly less force for screw pullout. The screw pullout force for the irradiated specimens and the ETO specimens did not significantly differ from their controls. These results indicate that freeze drying affected screw pullout strength. This method of processing should be questioned for structural allografts in which screw fixation is mandatory. The use of irradiation or ETO for sterilization may not have an adverse effect on screw pullout strength.

Biomechanical Phenomena↗

PubMed1991

The vascularity of the rotator cuff.

The major arterial supply to the rotator cuff is derived from the ascending branch of the anterior humeral circumflex artery, the acromial branch of the thoracoacromial artery, as well as the suprascapular and posterior humeral circumflex arteries. The pathogenesis of rotator cuff tears has been considered to be influenced by the microvascular supply of the rotator cuff tendons. Most cadaver studies have demonstrated a hypovascular area within the critical zone of the supraspinatus tendon. It has been suggested that this area of hypovascularity has a significant role in the attritional degeneration of the aging tendon. More recent studies of the microvascular supply to the supraspinatus tendon in symptomatic patients with impingement syndrome suggest that in the area of greatest impingement, i.e., the critical zone, there is actually hypervascularity. In contrast to the cadaver investigations, these studies seem to imply that hypervascularity or neovascularization is associated with symptomatic rotator cuff disease secondary to mechanical impingement.

Humans↗