Increasing expression of hypoxia-inducible proteins in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence.

Hypoxia-associated markers are involved in the progression of several malignancies, but are relatively unstudied in Barrett's carcinogenesis. Our aim was to assess the immunohistochemical expression of hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, erythropoietin (Epo), Epo receptor (Epo-R), Glut-1 and vascular endothelial growth factor (VEGF) along with Ki67/MIB-1 in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. Endoscopic biopsies of normal squamous epithelium (NSE) (n=20), columnar-lined oesophagus (CLO) (n=15), CLO with intestinal metaplasia (n=20), dysplasia (n=17) and Barrett's type adenocarcinoma (n=20) were obtained.

Expression of a non-DNA-binding Ikaros isoform exclusively in B cells leads to autoimmunity but not leukemogenesis.

Ikaros is a transcriptional regulator whose function is essential for B cell development. It is expressed in the hematopoietic stem cell (HSC) through the mature B cell stage. Using genetically engineered mice in which the endogenous Ikaros gene is disrupted, it has been shown that a lack of Ikaros leads to a block in B cell development and that its severe diminution results in a hyperresponsive B cell compartment.

Hypoxia-inducible factor-1alpha expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas.

Hypoxia-inducible factor-1 (HIF-1)alpha expression was studied in the gastric carcinogenesis sequence and as a prognostic factor in surgically resected gastric and gastro-oesophageal junction tumours. Protein expression was examined using immunohistochemistry on formalin-fixed biopsies of normal mucosa (n=20), Helicobacter pylori associated gastritis (n=24), intestinal metaplasia (n=24), dysplasia (n=12) and intestinal (n=19) and diffuse (n=21) adenocarcinoma. The relationship between HIF-1alpha expression and prognosis was assessed in resection specimens from 177 patients with gastric and gastro-oesophageal junction adenocarcinoma.

Emerging aspects of oesophageal and gastro-oesophageal junction cancer histopathology - an update for the surgical oncologist.

Adenocarcinoma of the oesophagus and gastro-oesophageal junction are rapidly increasing in incidence and have a well described sequence of carcinogenesis: the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. During recent years there have been changes in the knowledge surrounding disease progression, cancer management and histopathology specimen reporting. Tumours around the gastro-oesophageal junction (GOJ) pose several specific challenges.

Dietetic guidelines on food and nutrition in the secondary prevention of cardiovascular disease - evidence from systematic reviews of randomized controlled trials (second update, January 2006).

Aim: To update dietetic guidelines based on systematic review evidence on dietary advice to prevent further events in people with existing cardiovascular disease (CVD) (secondary prevention).

Methods: The Cochrane Library, MEDLINE and EMBASE were comprehensively searched to January 2005 for systematic reviews on aspects of diet and heart health. Reviews were included if they searched systematically for randomized controlled trials relating to diet and secondary prevention of CVD.

Chlamydiae-specific proteins and indels: novel tools for studies.

Chlamydiae species are important human and animal pathogens. Their obligate intracellular mode of replication has precluded the use of genetic and molecular biological approaches for understanding their biology. Comparative genomics have identified many rare genetic changes consisting of whole proteins and conserved indels (i.

Assuring the quality, safety, and efficacy of DNA vaccines.

Scientists in academia whose research is aimed at the development of a novel vaccine or approach to vaccination may not always be fully aware of the regulatory process by which a candidate vaccine becomes a licensed product. It is useful for such scientists to be aware of these processes, as the development of a novel vaccine could be problematic as a result of the starting material often being developed in a research laboratory under ill-defined conditions. This chapter examines the regulatory process with respect to the development of a DNA vaccine.

ATP regulation in adult rat cardiomyocytes: time-resolved decoding of rapid mitochondrial calcium spiking imaged with targeted photoproteins.

The mechanisms that enable the heart to rapidly increase ATP supply in line with increased demand have not been fully elucidated. Here we used an adenoviral system to express the photoproteins luciferase and aequorin, targeted to the mitochondria or cytosol of adult cardiomyocytes, to investigate the interrelationship between ATP and Ca(2+) in these compartments. In neither compartment were changes in free [ATP] observed upon increased workload (addition of isoproterenol) in myocytes that were already beating.

Lateral transfers of serine hydroxymethyltransferase (glyA) and UDP-N-acetylglucosamine enolpyruvyl transferase (murA) genes from free-living Actinobacteria to the parasitic chlamydiae.

The chlamydiae are important human and animal pathogens which form a phylogentically distinct lineage within the Bacteria. There is evidence that some genes in these obligate intracellular parasites have undergone lateral exchange with other free-living organisms. In the present work, we describe two interesting cases of lateral gene transfer between chlamydiae and actinobacteria, which have been identified based on the shared presence of conserved inserts in two important proteins.

Bifid vermiform appendix: a case report.

Introduction: Appendiceal anomalies are extremely rare: they have a reported incidence of between 0.004% and 0.009% of appendectomy specimens.

Regulation and standardization of IPV and IPV combination vaccines.

Inactivated poliovirus vaccine (IPV) is not only increasingly used on a global basis but also is a component of many combination vaccines. Standardization and control of IPV continues to be a challenge for manufacturers and regulators. A rat immunogenicity assay is currently recommended by many authorities, including WHO, as the definitive in vivo potency.

Human cardiac myosin autoantibodies impair myocyte contractility: a cause-and-effect relationship.

The functional relevance of autoantibodies (Abs) against cardiac myosin (CM) in clinical idiopathic dilated cardiomyopathy (DCM) remains controversial. The study sought to determine effects of human Abs affinity-purified (AF) by immunoaffinity column chromotography on excitation-contraction coupling in isolated myocytes. Effects of CM-Abs from heart failure patients with DCM (n=19) and ischemic heart disease (IHD, n=19) on contractility, L-type Ca2+ current, and Ca2+ transients in continuously perfused rat ventricular myocytes were studied.

Combined endoscopic and laparoscopic approach for palliative resection of metastatic melanoma of the stomach.

Background: Metastatic tumours of the stomach present a clinical dilemma for the surgeon. Palliative surgical resection can alleviate symptoms and prolong survival in selected patients. However, previous studies have used open methods of surgical resection with potentially high morbidity and mortality.

The prognostic value of circumferential resection margin involvement in oesophageal malignancy.

Aim: Our aim was to assess the effect on survival of circumferential resection margin (CRM) involvement in patients with resected oesophageal malignancy.

Methods: Patients undergoing potentially curative oesophageal resection between January 1994 and December 2003 were retrospectively analysed. CRM status was defined as either clear or involved (microscopic tumour within 1 mm of the inked resection margin).

Tumor length as a prognostic factor in esophageal malignancy: univariate and multivariate survival analyses.

Background And Objectives: Gastrointestinal specialists generally feel that long esophageal tumors carry a worse prognosis and are likely to be more advanced than shorter lesions. Our aim was to investigate the relationship between histologically determined tumor length and aspects of tumor pathology and survival for patients with resected esophageal malignancy.

Methods: Three hundred and nine patients who underwent esophageal resection with curative intent in our unit between 1994 and 2003 were retrospectively analyzed.

BLAST screening of chlamydial genomes to identify signature proteins that are unique for the Chlamydiales, Chlamydiaceae, Chlamydophila and Chlamydia groups of species.

Background: Chlamydiae species are of much importance from a clinical viewpoint. Their diversity both in terms of their numbers as well as clinical involvement are presently believed to be significantly underestimated. The obligate intracellular nature of chlamydiae has also limited their genetic and biochemical studies.

In vitro and in vivo characterization of recombinant human butyrylcholinesterase (Protexia) as a potential nerve agent bioscavenger.

Previous studies in rodents and nonhuman primates have demonstrated that pretreatment with cholinesterases can provide significant protection against behavioral and lethal effects of nerve agent intoxication. Human butyrylcholinesterase (HuBuChE) purified from plasma has been shown to protect against up to 5 x LD50s of nerve agents in guinea pigs and non-human primates, and is currently being explored as a bioscavenger pretreatment for human use. A recombinant form of HuBuChE has been expressed in the milk of transgenic goats as a product called Protexia.

Molecular signatures in protein sequences that are characteristics of the phylum Aquificae.

Species of the phylum Aquificae are of great interest due to their strict extreme thermophilic growth characteristics. Presently, there is no known molecular characteristic which is unique to this group of bacteria. This work describes six conserved inserts and deletions (indels or signature sequences) in four widely distributed proteins that are distinctive features of species from the phylum Aquificae.

Is the hypoxia-inducible factor pathway important in gastric cancer?

Tumour hypoxia is well recognised in oncology to be a key factor resulting in treatment resistance and poor prognosis. Hypoxia leads to the expression of a number of gene products that are involved in tumour progression, invasion and metastasis formation. The most important of these proteins is thought to be hypoxia-inducible factor-1alpha (HIF-1alpha), which appears to be a master regulator of the cellular response to hypoxia.

Conserved indels in essential proteins that are distinctive characteristics of Chlamydiales and provide novel means for their identification.

All known chlamydiae are either proven human or animal pathogens or possess such potential. Due to increasing reports of chlamydiae diversity in the environment, it is important to develop reliable means for identifying and characterizing Chlamydiales species. The identification of environmental chlamydiae at present relies on their branching pattern in 16S rRNA trees, as well as 16S/23S consensus motifs which display variability.

Ikaros induces quiescence and T-cell differentiation in a leukemia cell line.

Ikaros is a hematopoietic cell-specific zinc finger DNA binding protein that plays an important role in lymphocyte development. Genetic disruption of Ikaros results in T-cell transformation. Ikaros null mice develop leukemia with 100% penetrance.

Evaluation of a pre-operative staging protocol in the management of colorectal carcinoma.

Objective: The optimum strategy for pre-operative staging of colorectal carcinoma (CRC) has yet to be defined. A protocol for staging CRC patients was set up in this hospital in 1998. The protocol included complete colonic visualization together with assessment of the liver and lung for potential metastatic disease.