The denervated stomach as an esophageal substitute is a contractile organ.

Objective: To determine whether the denervated stomach as an esophageal substitute is an inert conduit or a contractile organ.

Summary Background Data: The motor response of gastric transplants to deglutition suggests that the stomach pulled up to the neck acts as an inert organ.

Methods: The gastric motility of 11 healthy volunteers and 33 patients having either a gastric tube (GT) (n = 10) or their whole stomach (WS) (n = 23) as esophageal replacement was studied with perfused catheters during the fasting state, after a meal, and after intravenous administration of erythromycin lactobionate.

Inhibition of invasion of epithelial cells by Tiam1-Rac signaling.

Tiam1 encodes an exchange factor for the Rho-like guanosine triphosphatase Rac. Both Tiam1 and activated RacV12 promote invasiveness of T lymphoma cells. In epithelial Madin-Darby canine kidney (MDCK) cells, Tiam1 localized to adherens junctions.

Targeting of Tiam1 to the plasma membrane requires the cooperative function of the N-terminal pleckstrin homology domain and an adjacent protein interaction domain.

The Rho-like GTPases Cdc42, Rac, and Rho play key roles in the regulation of the actin cytoskeleton and are implicated in transcriptional activation and cell transformation. We have previously identified the invasion-inducing Tiam1 gene, which encodes an activator of Rac. In fibroblasts, Tiam1 induces Rac-mediated membrane ruffling, which requires the N-terminal pleckstrin homology (PHn) domain.

The guanine nucleotide exchange factor Tiam1 affects neuronal morphology; opposing roles for the small GTPases Rac and Rho.

The invasion-inducing T-lymphoma invasion and metastasis 1 (Tiam1) protein functions as a guanine nucleotide exchange factor (GEF) for the small GTPase Rac1. Differentiation-dependent expression of Tiam1 in the developing brain suggests a role for this GEF and its effector Rac1 in the control of neuronal morphology. Here we show that overexpression of Tiam1 induces cell spreading and affects neurite outgrowth in N1E-115 neuroblastoma cells.

Radical esophageal resection for adenocarcinoma arising in Barrett's esophagus.

Background: Esophagectomy with extensive lymph node dissection is the best way to give Barrett's patients with locally advanced adenocarcinoma a good chance of cure.

Material And Methods: Fifty-five patients underwent subtotal (n = 47) or distal (n = 8) esophagectomy for Barrett's adenocarcinoma (n = 43) or high-grade dysplasia (HGD) (n = 12). Thirteen patients (23.

Safe biotechnology. 8. Transport of infectious and biological materials. Working Party "Safety in Biotechnology" of the European Federation of Biotechnology.

The transport of infectious and biological material is regulated by a number of international organizations. This mini-review has been compiled to increase awareness within the scientific community of problems caused by differences in terminology (such as infectious materials/substances, biological products, diagnostic specimens, genetically modified microorganisms) and certain technical aspects of the main international guidelines, and to assist policy makers in the creation of harmonized guidelines. A list of relevant Internet resources has been compiled.

Current status and trends in laparoscopic antireflux surgery: results of a consensus meeting. The European Study Group for Antireflux Surgery (ESGARS).

Laparoscopic surgery for gastroesophageal reflux disease has replaced the open approach in several institutions, and it is likely to become the "standard" for treatment in the near future. Members of five European surgical centers with extensive experience in pathophysiological research, diagnostic testing, and conventional surgery for esophageal disease met after five years of experience in using laparoscopic antireflux surgery, and established a plan to evaluate the potential for consensus among the centers involved in the surgical management of the disease. The consensus process started with a pathophysiological assessment of the reporting requirements for diagnostic workup.

Regulated membrane localization of Tiam1, mediated by the NH2-terminal pleckstrin homology domain, is required for Rac-dependent membrane ruffling and C-Jun NH2-terminal kinase activation.

Rho-like GTPases, including Cdc42, Rac, and Rho, regulate signaling pathways that control actin cytoskeletal structures and transcriptional activation. The Tiam1 gene encodes an activator of Rac1, and similarly to constitutively activated (V12)Rac1, overexpression of Tiam1 in fibroblasts induces the formation of membrane ruffles. Tiam1 contains a Dbl homology (DH) domain and adjacent pleckstrin homology (PH) domain, hallmarks for activators of Rho-like GTPases.

Expression of Tiam-1 in the developing brain suggests a role for the Tiam-1-Rac signaling pathway in cell migration and neurite outgrowth.

During development proper neuronal migration and neurite extension are essential for the formation of functional neuronal networks. These processes require the reorganization of the cytoskeleton by modifying the dynamics of actin filaments and microtubules. The Rho subfamily of GTPases regulates actin cytoskeletal changes during development.

Video-assisted thoracic surgery (VATS) for cancer. Risk of parietal seeding and of early local recurrence.

Both parietal seeding and early local recurrence have been anecdotally (24 cases) reported in the surgical literature after video-assisted thoracic surgery (VATS) for cancer. However, not all the cases reported were undoubtedly related to the thoracoscopic approach itself, several of those thoracoscopic procedures addressed locally advanced neoplastic processes, and protective measures against parietal contamination were not taken in one half of the patients. Strict adherence to the classic principles of carcinologic surgery should minimize the risk of both parietal and pleural grafting after VATS for cancer.

New insights into the assessment of gastro-oesophageal reflux disease.

Surgeons now have at their disposal various techniques to investigate both function and anatomy of the foregut in patients suspected to have gastro-oesophageal reflux disease (G.O.R.

Heller-Dor procedure for achalasia: from conventional to video-endoscopic surgery.

A Heller-Dor procedure was performed by laparotomy (group A: n = 8) or by laparoscopy (group B: n = 12) after failure of one to 17 sessions of intraluminal dilatations (n = 13) or as a primary treatment of oesophageal achalasia (n = 7). The oesophagomyotomy was extended over the thoracic oesophagus by thoracoscopy in two patients having vigorous achalasia. Injury to the oesophageal mucosa occurred in two group A patients who had previously been dilated.

Signaling pathways regulated by Rho-like proteins.

Small GTP-binding proteins of the Rho-subfamily, including Cdc42, Rac1 and RhoA, are key control molecules in the reorganization of the actin cytoskeleton induced by growth factors. Recent studies indicate that signal transduction pathways regulated by Rho-like GTPases are interconnected with the Ras-Raf-MAPkinase pathway, and play a role in several kinase pathways that lead to transcriptional activation and oncogenic transformation. Moreover, pathways regulated by Rac are involved in the acquisition of invasive and metastatic capacity of tumor cells.

[Lymph node excision in cancer of the esophagus].

This paper analyses the surgical literature devoted to lymph node clearance for cancer of the esophagus. Involvement of a small number of lymph nodes by the neoplastic process does not preclude long-term survival and even cure. The superiority of the 3-field dissection over the 2-field dissection, although suggested in the available studies, should be confirmed by a prospective randomized study.

Oncogenic activity of Tiam1 and Rac1 in NIH3T3 cells.

We have recently identified the invasion-inducing Tiam1 gene by proviral insertional mutagenesis. The Tiam1 protein shares a Dbl homology (DH) domain with an increasing number of oncoproteins, some of which have been shown to function as GDP dissociation stimulators (GDS) for small GTPases of the Rho family. In vitro and in vivo analyses indicate that Tiam1 activates the Rho like GTPase Rac1.

Carcinoembryonic antigen measurements in the management of esophageal cancer: an indicator of subclinical recurrence.

Background: Detection of subclinical recurrence after surgical resection of esophageal cancer would allow earlier treatment of recurrent disease and potentially offer a better outcome for rescue therapy.

Methods: The utility of serum carcinoembryonic antigen (CEA) assay was evaluated in the management of patients with esophageal cancer.

Results: Serum carcinoembryonic antigen was measured preoperatively in 74 patients.

Extensive lymph node clearance for cancer of the esophagus or cardia: merits and limits in reference to 5-year absolute survival.

Background/aims: The present study evaluates both merits and limits of extensive lymph node clearance in the mediastinum and upper abdomen on patients operated on more than 5 years ago.

Materials And Methods: One hundred forty-four esophageal cancer patients underwent subtotal (n = 97) or distal (n = 47) esophageal resection more than 5 years ago. Twenty-six patients operated on in a curative attempt were given radiotherapy (n = 14) or radiochemotherapy (n = 12).

Esophageal replacement: gastric tube or whole stomach?

Background: The stomach can be used either in its entirely or as a greater curvature tube for esophageal replacement.

Methods: The study compares the gastric tube (group A; n = 112) to the whole stomach whose lesser curvature is denuded (group B; n = 100) in terms of technical complication and alimentary comfort. The clinical results are substantiated by assessment of the eating performance of patients and control subjects at a test meal, measurement of the gastric dimensions before and after both tailoring procedures, and intraarterial staining of the gastric wall.

EO9: relationship between DT-diaphorase levels and response in vitro and in vivo.

EO9 [3-hydroxy-5-aziridinyl-1-methyl-2(1H-indole-4,7-dione)-prop-beta-en- alpha-ol] was selected for clinical trial in Europe because of its preclinical profile but also because of its distinct mechanism of bioactivation. Several studies have shown that cells rich in DT-diaphorase may be particularly sensitive to EO9. The present study examined the relationship between DT-diaphorase activity and sensitivity to EO9 in a panel of cell lines largely derived from human and rodent leukaemias/lymphoma and solid tumours.

A role for Rac in Tiam1-induced membrane ruffling and invasion.

Rho-like GTPases have been implicated in the regulation of the actin cytoskeleton which controls the morphology, adhesion and motility of cells. Like Ras proteins, they become activated when bound GDP is exchanged for GTP, a process catalysed by GDP-dissociation stimulator (GDS) proteins. Several GDS proteins specific for Rho-like GTPases have been identified.

Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a degenerative disease of motor neurons, characterized by depositions of neurofilaments in the perikarya and proximal axons. The pathogenesis of ALS remains poorly understood, but two lines of evidence suggest that neurofilament accumulation may play a causal role. First, transgenic mice that overexpress neurofilament proteins show motor neuron degeneration and, second, variant alleles of the neurofilament heavy-subunit gene (NF-H) have been found in some human ALS patients.

Mice overexpressing the human neurofilament heavy gene as a model of ALS.

We discuss the evidence, based on the analysis of transgenic mice overexpressing the human neurofilament (NF) heavy gene, that abnormal NF accumulations can provoke neurodegeneration of motor neurons. Transgenic mice overexpressing by two-fold the normal levels of human NF-H proteins develop a progressive motor neuron disease with several pathologic features reminiscent of those found in amyotrophic lateral sclerosis (ALS). A plausible mechanism for the selective motor neuron degeneration is that exceeding levels of NF-H cross-linkages impede transport of newly synthesized NF structures.

Sequence of the human invasion-inducing TIAM1 gene, its conservation in evolution and its expression in tumor cell lines of different tissue origin.

By means of proviral tagging in combination with in vitro selection for invasive T-lymphoma variants, we have previously identified the murine invasion- and metastasis-inducing Tiam1 gene. Tiam1 encodes a novel protein which shares a Dbl-homology (DH) domain with GDP dissociation stimulator-(GDS) proteins that activate Rho-like GTPases. We have cloned the human TIAM1 coding sequence and studied its evolutionary conservation and expression pattern.