von Willebrand factor proteolytic processing and multimerization precede the formation of Weibel-Palade bodies

We investigated the intracellular site of pro-von Willebrand factor (pro-vWF) cleavage and multimerization, as well as the fate of the propolypeptide (von Willebrand antigen II) after cleavage. Analysis of subcellular fractions of endothelial cells metabolically labeled with sulfate showed that both cleavage and covalent multimerization occur after sulfation and precede the formation of Weibel-Palade bodies. Because sulfation is a processing step localized to the trans-Golgi network (TGN), our results indicate that multimerization and prosequence cleavage also occur in this organelle. After cleavage, the propolypeptide remains noncovalently associated with the mature vWF subunit. This association is promoted by a high calcium concentration and an acidic pH (conditions thought to prevail in the TGN) and explains the 1:1 stoichiometry of the propolypeptide and mature vWF found in Weibel-Palade bodies. The propolypeptide remains an integral part of the large multimeric vWF aggregates in the Weibel-Palade body until secretion. When secretion occurs under slightly acidic conditions, such as may be found in poorly perfused wounds, the propolypeptide remains associated with the endothelial surface-bound vWF, and may thus participate in the wound healing process.     

Effects of verapamil on in vitro intracellular accumulation and retention of daunorubicin in blast cells from patients with acute nonlymphocytic leukemia

The effects of verapamil on the intracellular pharmacokinetics of daunorubicin (DNR) in blast cells from the bone marrows of patients with acute nonlymphocytic leukemia (ANLL) were studied to determine whether verapamil was capable of enhancing intracellular accumulation and retention of DNR in ANLL, as has been observed in murine P388 cells resistant to DNR. Seventeen marrows from ANLL patients were studied, 13 of which were from patients who were considered to be clinically refractory to DNR. We took care to include such patients in this study since, in the P388 model, verapamil enhancement of DNR uptake is observed only in cells resistant to DNR. Intracellular accumulation of DNR was studied by exposing blast cells to DNR (1 microgram/mL) +/- verapamil (6.6 mumol/L) for up to 4 hours. Following a 2-hour exposure of cells to DNR +/- verapamil, intracellular retention of DNR was studied by incubating the cells in DNR-free medium for 3 hours. Intracellular DNR/10(6) cells was quantified by fluorometry. In 12 of 15 patient marrows, verapamil failed to enhance intracellular accumulation of DNR. Three patient marrows had a very small increment in DNR uptake in response to verapamil (approximately 14% greater than DNR alone) that was significant (P less than .05) by paired t test. Intracellular retention of DNR (t 1/2) and the area under the intracellular DNR v time curve (AUC) were studied in 17 patients marrow specimens. No significant alterations in these parameters were observed in response to verapamil. These data indicate either that verapamil did not substantially enhance DNR uptake or retention in blast cells obtained from ANLL patients who are clinically resistant to DNR, or that the frequency of DNR-resistant cells (ie, verapamil-responsive cells) among the blast cells obtained from these patients was too low to influence the population mean of intracellular DNR as measured in these studies.     

Colorectal carcinoma: a radiologic and clinical review

A profusion of imaging techniques is currently used for evaluating patients with suspected or known colorectal carcinoma. In most institutions, the combination of flexible sigmoidoscopy and a well-performed barium enema study should be retained as a more cost-effective, safe, and complete method of examination than colonoscopy. Endosonography appears to be promising for evaluating preoperatively the local extent of rectal carcinoma. CT is being challenged by MR imaging as the most sensitive modality for detecting liver metastases, but CT currently remains the technique of choice for evaluating recurrent disease and its extent. The diversity of available modalities will ensure that the radiologist remains at the forefront in the clinical investigation of colorectal carcinoma.     

Peripheral blood stem cell collection and use in Hodgkin''s disease. Comparison with marrow in autologous transplantation

Hematopoietic progenitor cells can be collected from blood by cytapheresis; the clinical use of these cells may offer such advantages over marrow as the avoidance of general anesthesia, collection on an outpatient basis, and use when marrow is involved with malignancy. Since Hodgkin's disease rarely spreads hematogenously, postchemotherapy marrow transplantation with autologous peripheral blood stem cells (PBSCs) was compared to that with marrow transplantation in patients with this disorder. Seven patients were treated with PBSCs and 19 with marrow. Five to nine collections of PBSC were performed per patient. There was a rebound increase in circulating committed progenitors when PBSC were collected during the marrow rebound after cyclic chemotherapy. After intensification and cellular rescue, quicker recovery of circulating white cells (p less than 0.05) and a shorter hospital stay (not significant) were seen in the PBSC patients than in those treated with autologous marrow. There was no difference in the duration of red cell or platelet transfusion required after transplant. Of six patients whose marrows were previously involved by Hodgkin's, recurrent or progressive disease has occurred in five. PBSC may be a viable alternative to marrow in selected patients.     

Jejunal fold separation in adult celiac disease: relevance of enteroclysis

The number of folds in the proximal jejunum was measured retrospectively in 25 studies of patients with adult celiac disease and 75 control subjects. The average number of folds per inch of proximal jejunum in the group with celiac disease was 2.88 (none to five), as against 4.88 (three to seven) in the controls. The difference was less pronounced in the distal ileum. A "mosaic pattern" was demonstrated in three patients. Positive radiologic evidence of celiac disease could be elicited in 76% of the patients' studies. Demonstration of five or more folds in the jejunum and/or three or fewer folds in the ileum would have been evidence against a diagnosis of celiac disease in 67 of the 75 controls. Indications for the use of radiography in celiac disease are reassessed.     

Intubation routes for enteroclysis

The transnasal and peroral intubation routes for enteroclysis examination are described. A survey of 22 patients who underwent enteroclysis by both approaches revealed an overwhelming preference for the transnasal route. Transnasal intubation for enteroclysis is rapidly performed with adequate catheter control and in most patients is associated with less discomfort compared with the peroral route.