Release of soluble transferrin receptor from the surface of human leukemic HL60 cells

Information regarding transferrin (Tf) receptor degradation is largely incomplete. HL60 cells were shown to release to their growth medium a Tf-binding protein which could be immunoprecipitated by anti-Tf receptor monoclonal antibodies (MoAbs) B3/25 and OKT9. Soluble Tf receptor was detected in the medium within one hour of replating of cells, and its release was inhibited at 4 degrees C. The affinity of Tf for the soluble receptor released by cells (kd = 2.3 x 10(-10) mol/L) was slightly lower than its affinity for the detergent-solubilized cellular receptor (kd = 1.2 x 10(-10) mol/L). 125I-Tf internalized and released by cells subsequently bound to Tf receptor released by the same cells, and soluble Tf receptor in the conditioned medium (CM) inhibited 125I-Tf binding to intact cells. The soluble Tf receptor isolated from the CM was smaller (78,000 daltons) than the cell surface receptor (94,000 daltons) when analyzed by gel electrophoresis under reducing conditions. Isolated cell membranes readily released soluble receptor; however, this release could be blocked by protease inhibitors. The soluble Tf receptor may represent the extracytoplasmic domain of the cellular Tf receptor released from the surface of HL60 cells through proteolytic cleavage by a membrane-based protease.     

Effects of haloperidol on motor and cognitive functioning in aged mice

The effects of haloperidol on motor and functioning and cognitive functioning were studied in young (3-5 months old) and aged (20-22 months old) male mice by examining haloperidol-induced catalepsy and haloperidol-induced decrements in performance on a radial arm maze. The aged mice were much more sensitive to these adverse effects of haloperidol than were the young mice. Studies of the distribution of radioactivity from [3H]haloperidol to the brain indicated that the differences in sensitivity to this drug were not due to pharmacokinetic differences. The results demonstrate that mice are suitable for studies of aging-induced changes in the behavioral effects of neuroleptic agents.     

Pneumothorax and other lung diseases: effect of altered resolution and edge enhancement on diagnosis with digitized radiographs

Prior studies have shown that pneumothorax is one of the more difficult entities to diagnose with digitized radiography. This study was designed to test whether increasing resolution from 1.25 to 2.5 line pairs per millimeter (lp/mm) and image processing (edge enhancement from unsharp masking) would increase accuracy and confidence in the diagnosis of pneumothorax, as well as normal cases and other forms of lung disease. Conventional radiographs were digitized with use of a laser reader and then reformatted as film hard copy. Eleven observers read 35 cases reformatted in three different ways (1.25 lp/mm, 2.5 lp/mm, 1.25 lp/mm unsharp mask). The images with finer resolution (2.5 lp/mm) and unsharp mask images were superior to those with coarser resolution (1.25 lp/mm) for the diagnosis of pneumothorax. There was no difference in diagnostic accuracy for normal patients. For abnormalities other than pneumothorax, the unsharp mask images were significantly worse. Confidence in the diagnosis of pneumothorax and other abnormalities was highest with the finest resolution (2.5 lp/mm).     

Characteristics of rejection of orthotopic corneal allografts in the rat

We have employed a rat model of orthotopic corneal transplantation to study the characteristics of rejection and development of systemic immunity in the host. Lewis (LEW) rats underwent a true penetrating keratoplasty using Wistar-Furth (WF) donor corneas. A rejection incidence of 55% with a mean survival time (MST) of 17.1 days was observed using these untreated allogeneic corneas. Animals undergoing rejection of these allografts developed cytotoxic T lymphocytes (CTL) capable of lysing WF lymphoblasts in a standard 51-chromium release assay. These same rats did not have delayed-type hypersensitivity (DTH) responses when compared to skin grafted controls. Rats with clear allografts had no demonstrable CTL or DTH activity. As expected, LEW rats that were preimmunized with WF skin grafts and subsequently received WF orthotopic corneal grafts rejected 100% of these corneas at an accelerated rate (MST = 9.7 days, P less than .02). We then employed a previously described technique of using latex beads to induce migration of Langerhans cells into the central cornea of the donor graft prior to transplantation. The presence of Langerhans cells in the donor cornea resulted in a higher incidence of rejection (96%) and an accelerated rate (MST = 11.8 days, P less than .02) when compared to untreated allografts. These rats also had a higher level of CTL activity and marked DTH responses. These data show that rejection of orthotopic allogeneic corneas is accompanied by the development of systemic alloimmunity as measured by CTL activity. However, these fully allogeneic corneas can be rejected in the absence of DTH responses. Langerhans cells have a dramatic effect on graft survival and are necessary for induction of DTH responsiveness in the host.