Preoperative radiation therapy for locally advanced rectal cancer: a comparison between two different time intervals to surgery.

Background: Although it is now considered a standard treatment to irradiate an advanced mid or low rectal tumor before surgical total mesorectal excision (TME), the optimal time interval between radiation therapy and surgery remains controversial.

Materials And Methods: Between 1995 and 2005, patients undergoing preoperative radiation therapy and TME for locally advanced mid and low rectal tumors treated in the VU Medical Center or the Zaans Medical Center were entered into this study. All patients received identical radiation treatment in the VU Medical Center and were subsequently operated on within 2 weeks in the Zaans Medical Center (SI group) and after 6-8 weeks in the VU Medical Center (LI group).

Minimally invasive oesophageal resection for distal oesophageal cancer: a review of the literature.

Oesophagus resection is adequate treatment for some benign oesophageal diseases, especially caustic and peptic stenosis and end-stage motility dysfunction. However, the most frequent indications for oesophageal resection are the high-grade dysplasia of Barrett oesophagus and non-metastasized oesophageal cancer. Different procedures have been developed for performing oesophageal resection given the 5-year survival rate of only 18% among patients operated on.

Self-expanding metal stents for the treatment of intrathoracic esophageal anastomotic leaks following esophagectomy.

Intrathoracic anastomotic leakage following resection for esophageal malignancy is associated with significant morbidity and mortality rates. Recently, therapy consisted mainly of surgical reexploration and conservative treatment using nasogastric and perianastomotic drainage. This case report shows the feasibility of using fully covered metal esophageal stents to close the anastomotic defect in three patients with esophagectomy for cancer.

Cell-specific regulation of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha stabilization and transactivation in a graded oxygen environment.

The hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha are closely related, key transcriptional regulators of the hypoxic response, countering a low oxygen situation with the up-regulation of target genes associated with numerous processes, including vascularization and glycolysis. This involves a dual mechanism of control through both stabilization and transactivation, regulated via prolyl and asparaginyl hydroxylation. Despite high similarity with respect to protein sequence and activation pathway, a growing number of physiological and mechanistic differences between HIF-1alpha and HIF-2alpha are being reported.

Regulation of HIF: asparaginyl hydroxylation.

The hypoxia inducible transcription factors (HIFs) are regulated at the level of protein stability and transcriptional activity in an oxygen-dependent manner by prolyl and asparaginyl hydroxylation, respectively. Factor inhibiting HIF (FIH-1) is the only known HIF asparaginyl hydroxylase, and targets a conserved asparaginyl residue within the C-terminal activation domain (CAD) of HIF-alpha. This represses HIF-mediated transcription by inhibiting the recruitment of p300/CBP coactivators.

Retrospective review of the epidemiology of epilepsy in special schools for children with cerebral palsy, learning difficulties, and language and communication difficulties.

Purpose Of The Study: To determine in children the proportion and characteristics of epilepsy associated with cerebral palsy, learning difficulties and language and communication difficulties in a specific population of two special schools.

Basic Procedures: Retrospective review of case notes for 142 children in two special schools (school A and school B) in Newcastle, UK MAIN FINDINGS: School A had more children with learning difficulties (X2=32.41, p<0.

Activity of hypoxia-inducible factor 2alpha is regulated by association with the NF-kappaB essential modulator.

The hypoxia-inducible factors 1alpha (HIF-1alpha) and 2alpha (HIF-2alpha) are key regulators of the transcriptional response to low oxygen and are closely related in domain architecture, DNA binding, and activation mechanisms. Despite these similarities, targeted disruption of the HIF-alpha genes in mice results in distinctly different phenotypes demonstrating nonredundancy of function, although the underlying mechanisms remain unclear. Here we report on the novel and specific interaction of HIF-2alpha, but not HIF-1alpha, with the NF-kappaB essential modulator (NEMO) using immunoprecipitation, mammalian two-hybrid, and in vitro protein interaction assays.

Minimally invasive esophageal resection.

Esophagus resection is the adequate treatment for some benign esophageal diseases, especially caustic and peptic stenosis and end-stage motility dysfunction. However, the most frequent indications for esophageal resection are the high-grade dysplasia of Barrett esophagus and nonmetastasized esophageal cancer. Different procedures have been developed to perform esophageal resection given the 5-year survival rate among operated patients of only 18%.

Regulation of gene expression by the hypoxia-inducible factors.

Many molecular and physiological responses to hypoxia in mammals are controlled by the transcription factors Hypoxia-Inducible Factor-1alpha (HIF-1alpha) and HIF-2alpha. Their ability to promote the transcription of hypoxia-inducible genes is mediated by protein stability and regulation of a C-terminal transactivation domain. Oxygen-dependent hydroxylation of conserved proline and asparagine residues in HIF-alpha are required for targeting HIF-alpha to proteasomes for destruction, and for inhibiting its capacity for CBP/p300-dependent transactivation, respectively.

Substrate requirements of the oxygen-sensing asparaginyl hydroxylase factor-inhibiting hypoxia-inducible factor.

The hypoxia-inducible factor alpha subunits 1 and 2 (HIF-1alpha and HIF-2alpha) are subjected to oxygen-dependent asparaginyl hydroxylation, a modification that represses the carboxyl-terminal transactivation domain (CAD) at normoxia by preventing recruitment of the p300/cAMP-response element-binding protein coactivators. This hydroxylation is performed by the novel asparaginyl hydroxylase, factor-inhibiting HIF-1' (FIH-1), of which HIF-1alpha and HIF-2alpha are the only reported substrates. Here we investigated the substrate requirements of FIH-1 by characterizing its subcellular localization and by examining amino acids within the HIF-1alpha substrate for their importance in recognition and catalysis by FIH-1.

The hypoxia-inducible factors: key transcriptional regulators of hypoxic responses.

Oxygen depravation in mammals leads to the transcriptional induction of a host of target genes to metabolically adapt to this deficiency, including erythropoietin and vascular endothelial growth factor. This response is primarily mediated by the hypoxia-inducible factors (HIFs) which are members of the basic-helix-loop-helix/Per-ARNT-Sim (bHLH/PAS) transcription factor family. The HIFs are primarily regulated via a two-step mechanism of HIF post-translational modification, increasing both protein stability and transactivation capacity.

Defining the role for XAP2 in stabilization of the dioxin receptor.

The dioxin receptor (DR) is a ligand-activated transcription factor that is activated upon binding of dioxins or structurally related forms of xenobiotics. Upon binding ligand the DR translocates from the cytoplasm to the nucleus where it complexes with the partner protein Arnt to form a DNA binding heterodimer, which activates transcription of target genes involved in xenobiotic metabolism. Latency of the DR signaling pathway is maintained by association of the DR with a number of molecular chaperones including the 90-kDa heat shock protein (hsp90), the hepatitis B virus X-associated protein (XAP2), and the 23-kDa heat shock protein (p23).

Concentrations of carotenoids, retinol and alpha-tocopherol in plasma and follicular fluid of women undergoing IVF.

Background: Carotenoids are transferred into follicular fluid where they might serve as antioxidants and/or as precursors of retinoids which might modulate follicular or oocyte functions.

Methods And Results: In 77 women undergoing IVF differences between plasma and follicular fluid in the levels of carotenoids, retinol and alpha-tocopherol were evaluated especially with regard to fertilization success. Concentration of total carotenoids, retinol and alpha-tocopherol determined by HPLC in follicular fluid and plasma were 0.

Quantitative assessment of the radiation hazards and risks in sentinel node procedures.

Sentinel node localization using an injected radiopharmaceutical and a gamma probe is performed in many hospitals. Employers have a duty to give appropriate training to staff who may not have been previously formally trained to work with unsealed radioactive sources. A study was performed to assess hazards and risks at all stages of the localization procedure.

Oxygen-dependent regulation of hypoxia-inducible factors by prolyl and asparaginyl hydroxylation.

To sustain life mammals have an absolute and continual requirement for oxygen, which is necessary to produce energy for normal cell survival and growth. Hence, maintaining oxygen homeostasis is a critical requirement and mammals have evolved a wide range of cellular and physiological responses to adapt to changes in oxygen availability. In the past few years it has become evident that the transcriptional protein complex hypoxia-inducible factor (HIF) is a key regulator of these processes.

Endoscopic treatment of benign esophageal tumors: case report of three patients.

Benign esophageal tumors are rare. Enucleation of the tumor is considered when the patient reports problems. The traditional approach is to use thoracotomy or laparotomy if the tumor is located in the distal esophagus.

Albumin recovery with centrifugal adsorption technology (CAT).

Centrifugal adsorption technology (CAT) is a new compact, countercurrent technology for efficient adsorption from large liquid streams by using adsorbent particles in the micrometer range. CAT seems particularly suited for the recovery of macromolecules at low concentrations, because the small particle dimensions lead to fast mass transfer rates. In this work, the potential of CAT for protein recovery is studied by model and experiment.

Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch.

The hypoxia-inducible factors (HIFs) 1alpha and 2alpha are key mammalian transcription factors that exhibit dramatic increases in both protein stability and intrinsic transcriptional potency during low-oxygen stress. This increased stability is due to the absence of proline hydroxylation, which in normoxia promotes binding of HIF to the von Hippel-Lindau (VHL tumor suppressor) ubiquitin ligase. We now show that hypoxic induction of the COOH-terminal transactivation domain (CAD) of HIF occurs through abrogation of hydroxylation of a conserved asparagine in the CAD.

[Laparoscopic myotomy in 14 patients with achalasia after unsuccessful pneumatic dilatations: effective and safe].

Objective: Evaluation of laparoscopic myotomy with or without an anti-reflux (Dor) procedure in patients with achalasia.

Design: Retrospective.

Method: Data were collected from patients who underwent a laparoscopic myotomy for achalasia, following repeated pneumatic dilations.

Epiphrenic diverticula: minimal invasive approach and repair in five patients.

Epiphrenic esophageal diverticula are rare and often asymptomatic. If surgery is mandatory, a thoracotomy is used to resect the diverticulum. The results of a minimal invasive approach and repair in five patients are presented.

Laparoscopic treatment of large hiatal hernias.

Large hiatal or paraesophageal hernias constitute between 5% and 10% of all hiatal hernias. This hernia is a potential threatening complication, and a timely operative correction should be performed in all patients with an acceptable risk. Based on the lessons learned from conventional approach, laparoscopic treatment has confirmed the initial good results with all advantages of laparoscopic surgery.

Laparoscopic treatment of large paraesophageal hernias: both excision of the sac and gastropexy are imperative for adequate surgical treatment.

Background: We set out to evaluate the results of the laparoscopic treatment of large paraesophageal hernias in 22 patients.

Methods: Between 1993 and 1998, we operated on 22 consecutive patients. Preoperative assessment consisted of endoscopy, barium esophagogram, 24-h pH testing, manometry, and gastric emptying times.