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1.
Indian J Orthop ; 50(6): 616-621, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27904216

RESUMEN

BACKGROUND: Multiple reconstruction techniques have been described in the management of chronic scapholunate (SL) instability, either based on the capsulodesis or tenodesis principle. It is uncertain which surgical method produces the best patient outcomes. We describe results of a technique using palmaris longus (PL) tendon for surgical reconstruction of the SL ligament and provide functional outcomes scores. MATERIALS AND METHODS: We surgically reconstructed the SL ligament using a PL tendon graft secured with Mitek® bone anchors. Surgical technique with photographs is provided in the main text. Functional outcomes were measured using the disabilities of the arm, shoulder, and hand and Mayo wrist scores. Patient satisfaction was assessed using a simple measure. RESULTS: Eleven patients attended mid-term followup (mean 45.8 months post-surgery) and had functional outcomes and satisfaction of this procedure that compared favorably to case series that used tenodesis for chronic SL ligament injuries. Almost all patients (n = 10) were able to return to regular employment. The majority of patients (n = 10) were satisfied with their primary reconstruction procedure. CONCLUSION: This technique avoids the use of drill holes to weave tendon through bone, uses an easy to access graft, and exploits the superior pullout strength of anchors while offering satisfactory functional outcomes that are comparable to alternative tenodesis techniques.

2.
PLoS One ; 10(8): e0134645, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26262842

RESUMEN

General activation of hypoxia-inducible factor (HIF) pathways is classically associated with adverse prognosis in cancer and has been proposed to contribute to oncogenic drive. In clear cell renal carcinoma (CCRC) HIF pathways are upregulated by inactivation of the von-Hippel-Lindau tumor suppressor. However HIF-1α and HIF-2α have contrasting effects on experimental tumor progression. To better understand this paradox we examined pan-genomic patterns of HIF DNA binding and associated gene expression in response to manipulation of HIF-1α and HIF-2α and related the findings to CCRC prognosis. Our findings reveal distinct pan-genomic organization of canonical and non-canonical HIF isoform-specific DNA binding at thousands of sites. Overall associations were observed between HIF-1α-specific binding, and genes associated with favorable prognosis and between HIF-2α-specific binding and adverse prognosis. However within each isoform-specific set, individual gene associations were heterogeneous in sign and magnitude, suggesting that activation of each HIF-α isoform contributes a highly complex mix of pro- and anti-tumorigenic effects.


Asunto(s)
Hipoxia/metabolismo , Neoplasias Renales/metabolismo , Transducción de Señal , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Sitios de Unión , Línea Celular Tumoral , Expresión Génica , Humanos , Factor 1 Inducible por Hipoxia/genética , Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Renales/genética , Neoplasias Renales/mortalidad , Pronóstico , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Activación Transcripcional
3.
Biol Chem ; 394(4): 507-17, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23324384

RESUMEN

Hypoxia-inducible transcription factors (HIFs) mediate the cellular response to hypoxia. HIF-DNA binding triggers a transcriptional program that acts to both restore oxygen homeostasis and adapt cells to low oxygen availability. In this context, HIF is centrally involved in many physiologic and pathophysiological processes such as development, high altitude adaptation, ischemic disease, inflammation, and cancer. The recent development of chromatin immunoprecipitation coupled to genome-wide DNA sequence analysis allows the position and extent of HIF binding to DNA to be characterized across the entire genome and correlated with genetic, epigenetic, and transcriptional analyses. This review summarizes recent pan-genomic analyses of HIF binding and HIF-dependent transcriptional regulation.


Asunto(s)
Hipoxia/metabolismo , Animales , Inmunoprecipitación de Cromatina , Humanos , Factor 1 Inducible por Hipoxia/metabolismo , Modelos Biológicos , Transcripción Genética/genética
4.
Semin Cancer Biol ; 13(1): 83-9, 2003 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-12507560

RESUMEN

Recently, work on the mechanism of action of the von Hippel-Lindau tumour suppressor protein (pVHL) and studies on hypoxic gene regulation have converged, providing insights into both cellular oxygen sensing and cancer pathogenesis. pVHL is the recognition component of the E3-ubiquitin ligase complex involved in the degradation of hypoxia-inducible factor-1 (HIF) alpha-subunits, a process regulated by oxygen availability and blocked by disease causing pVHL mutations. In normoxic cells, pVHL targeting of HIF-alpha subunits follows hydroxylation of critical HIF prolyl residues by a group of oxygen, 2-oxoglutarate- and iron-dependent enzymes. In this review, we outline current understanding of HIF/pVHL/prolyl hydroxylase pathway and consider the implications for VHL-associated cancer.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Ligasas/metabolismo , Neoplasias/fisiopatología , Proteínas Nucleares/metabolismo , Factores de Transcripción , Proteínas Supresoras de Tumor , Ubiquitina-Proteína Ligasas , Regulación de la Expresión Génica/fisiología , Genes Supresores de Tumor/fisiología , Humanos , Hipoxia/genética , Hipoxia/metabolismo , Factor 1 Inducible por Hipoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau , Enfermedad de von Hippel-Lindau/genética , Enfermedad de von Hippel-Lindau/fisiopatología
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