Bacterial lipopolysaccharide can enter monocytes via two CD14-dependent pathways

Host recognition and disposal of LPS, an important Gram-negative bacterial signal molecule, may involve intracellular processes. We have therefore analyzed the initial pathways by which LPS, a natural ligand of glycosylphosphatidylinositol (GPI)-anchored CD14 (CD14-GPI), enters CD14-expressing THP-1 cells and normal human monocytes. Exposure of the cells to hypertonic medium obliterated coated pits and blocked 125I-labeled transferrin internalization, but failed to inhibit CD14-mediated internalization of [3H]LPS monomers or aggregates. Immunogold electron microscope analysis found that CD14-bound LPS moved principally into noncoated structures (mostly tubular invaginations, intracellular tubules, and vacuoles), whereas relatively little moved into coated pits and vesicles. When studied using two-color laser confocal microscopy, internalized Texas Red-LPS and BODIPY-transferrin were found in different locations and failed to overlap completely even after extended incubation. In contrast, in THP-1 cells that expressed CD14 fused to the transmembrane and cytosolic domains of the low-density lipoprotein receptor, a much larger fraction of the cell-associated LPS moved into coated pits and colocalized with intracellular transferrin. These results suggest that CD14 (GPI)-dependent internalization of LPS occurs predominantly via noncoated plasma membrane invaginations that direct LPS into vesicles that are distinct from transferrin-containing early endosomes. A smaller fraction of the LPS enters via coated pits. Aggregation, which greatly increases LPS internalization, accelerates its entry into the nonclathrin-mediated pathway.     

Framestore system for map displays

The map displays project was undertaken to investigate techniques for the storage and display of geographical maps and related information and to develop the hardware and software required for a complete working system. Initially most of the project was concerned with the design of graphics hardware to be interfaced to a DEC LSI-11/03 micro-computer which was the main supply of computing power for the project. The development of one of the pieces of specialized hardware, the framestore display, is described.     

Hospital-associated bacterial meningitis

Eighteen of 349 cases (5.2 per cent) of bacterial meningitis seen between 1949 and 1973 were hospital-associated (developed after admission to the hospital). The patients were adults, usually males, and developed symptoms and signs of meningitis from 2 to 23 days (mean, 10.1 days) after hospital admission. The diagnosis of bacterial meningitis was made from less than 1 day to 15 days (mean, 4.8 days) after the onset of symptoms. Fourteen of the 18 patients had received antibiotics during the week prior to developing meningitis. Nine (50 per cent) had a chronic, noninfection, underlying illness. Diagnostic or surgical procedures involving the neuraxis or adjacent structures preceded the development of meningitis in 10 of the 18 patients (56 per cent). Only 6 of the 18 patients survived their infection. Prompt recognition, diagnosis, and therapy of hospital-associated meningitis in high-risk patients may reduce the significant mortality.     

A diagnostic formula for alcoholism

Clinical pathologies with unusually high morbidities in alcoholic populations were analyzed to determine their capacity to diagnose alcoholism. On the basis of five systemic variables it was possible to diagnose correctly nearly 75% of alcoholic and matched control subjects.