beta1-integrin mediates myelin-associated glycoprotein signaling in neuronal growth cones

Several myelin-associated factors that inhibit axon growth of mature neurons, including Nogo66, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp), can associate with a common GPI-linked protein Nogo-66 receptor (NgR). Accumulating evidence suggests that myelin inhibitors also signal through unknown NgR-independent mechanisms. Here we show that MAG, a RGD tri-peptide containing protein, forms a complex with β1-integrin to mediate axonal growth cone turning responses of several neuronal types. Mutations that alter the RGD motif in MAG or inhibition of β1-integrin function, but not removal of NgRs, abolish these MAG-dependent events. In contrast, OMgp-induced repulsion is not affected by inhibition of b1-integrin function. We further show that MAG stimulates tyrosine phosphorylation of focal adhesion kinase (FAK), which in turn is required for MAG-induced growth cone turning. These studies identify β1-integrin as a specific mediator for MAG in growth cone turning responses, acting through FAK activation.     

Enhancement of swine progenitor chimerism in mixed swine/human bone marrow cultures with swine cytokines.

OBJECTIVE: The induction of transplantation tolerance across xenogeneic barriers by bone marrow transplantation holds great promise, but engraftment of xenogeneic stem cells has been difficult to achieve. Part of this difficulty is due to species-specific differences in regulatory cytokines and elements of the stromal microenvironment, which we studied here. MATERIALS AND METHODS: We developed a system where fresh bone marrow cells from swine and human are cultured on human bone marrow stroma in order to study these limiting factors in a clinically relevant species combination. RESULTS: We report here the ability of recombinant swine interleukin (IL)-3 and c-kit ligand (KL) to specifically enhance swine hematopoietic chimerism in this system. In the absence of exogenous swine cytokines, there were about half as many swine progenitors as human progenitors at 1, 2, and 4 weeks of culture. When used alone, swine IL-3 led to a notable but transient increase in the relative ratio of swine progenitors, while addition of swine KL increased the ratio of swine progenitors only modestly and only at later time points. In contrast, when swine IL-3 and KL were added together, there was a two- to fourfold increase in the ratio of swine to human progenitors at all times tested. CONCLUSION: These data demonstrate that both swine IL-3 and KL are needed for prolonged enhancement of swine progenitor chimerism under these conditions, and suggest that the species specificity of either one or both of these cytokines may represent an important barrier to prolonged engraftment of swine bone marrow in humans.     

Peptic ulcer and gastric carcinoma: diagnosis with biphasic radiography compared with fiberoptic endoscopy

The diagnostic value of biphasic radiographic examination of the stomach and duodenum was compared with that of fiberoptic endoscopy in a prospective, blinded study of 385 patients with dyspepsia. This investigation was directed at gastric malignancies and peptic ulcers. Methodologically there is no absolute standard for a study of this kind because histologic examination is useful for detection of cancer but inadequate for ulcers. As an alternative, kappa indexes and the sensitivity and specificity, as derived by Hui and Walter, were calculated and compared. For the detection of gastric carcinoma, radiographic and endoscopic findings had almost perfect agreement beyond chance. For gastric ulcers, radiography and endoscopy had substantial agreement, which became perfect if small ulcers (less than 5 mm) were excluded. For duodenal ulcers, radiography had a lower sensitivity than endoscopy; this disagreement disappeared if small ulcers were excluded. Both methods have equal merit; choice of the initial diagnostic procedure will therefore depend on cost, discomfort to the patient, and risk of complications.     

Failure to awaken after general anaesthesia secondary to paradoxical venous embolus

A patient is presented who failed to regain consciousness after an apparently uneventful nine-hour revision of a total hip replacement. There were no clinically important haemodynamic changes during the operation, and oxygen saturation, capnography and acid base balance were normal throughout. Postop CT of the head showed a large left MCA infarct with midline shift. At autopsy, the patient was found to have a previously unsuspected patent foramen ovale, and a venous embolus in the left internal carotid artery, which probably had originated from the periprostatic venous plexus with a large infarct in the distribution of the left anterior and middle cerebral arteries. The authors conclude that massive paradoxical venous emboli can occur during surgery with minimal haemodynamic changes.     

Review of iliopsoas anatomy and pathology

The iliopsoas compartment acts as a conduit for the spread of disease within the body. Knowledge of its anatomy facilitates the early diagnosis of some potentially fatal lesions.     

Causes of jaundice during hepatic artery infusion chemotherapy

Jaundice develops in many patients with liver metastases from colorectal adenocarcinoma during hepatic arterial infusion chemotherapy (HAIC). The usual cause is thought to be hepatotoxicity from the chemotherapeutic agent or biliary obstruction from progressive neoplastic disease. The authors evaluated the abdominal computed tomography and ultrasound examinations performed on 49 patients who were jaundiced during long-term HAIC. In only one patient was diffuse intrahepatic biliary dilatation caused by an obstructing mass in the porta. Two patients had metastatic hepatic lesions causing focal biliary obstruction. Intrahepatic dilatation without an obstructing mass occurred in 20 patients. Percutaneous or endoscopic cholangiograms were commonly interpreted prospectively as showing extrinsic compression by metastases, but no mass was confirmed on imaging studies. Seven patients had focal intrahepatic ductal dilatation from stricture without an associated mass. The remaining 19 patients had normal-caliber ducts; their jaundice was caused by chemical hepatitis. This series suggests that the most common causes of jaundice in these patients are chemical hepatitis and common bile duct stricture, complications of intraarterial chemotherapy, rather than neoplastic obstruction. Stricture formation may be confused with extrinsic compression on direct cholangiograms.