Sequences present in the cytoplasmic domain of CD4 are necessary and sufficient to confer sensitivity to the human immunodeficiency virus type 1 Vpu protein

CD4 is an integral membrane glycoprotein which functions as the human immunodeficiency virus receptor for infection of human host cells. We have recently demonstrated that Vpu, a human immunodeficiency virus type 1-encoded integral membrane phosphoprotein, induces rapid degradation of CD4 in the endoplasmic reticulum. Using an in vitro model system, we demonstrated that Vpu targets specific sequences in the cytoplasmic domain of CD4 to promote its degradation. In this report, we have further delineated regions within CD4 which are required for susceptibility to Vpu. Transfer of the CD4 cytoplasmic region into a heterologous protein, CD8, rendered the chimeric protein sensitive to Vpu-dependent degradation. In contrast, substitution of the CD8 transmembrane domain with the analogous region from CD4 did not confer sensitivity to Vpu. Finally, mutant forms of the CD4 protein containing the extracellular region alone or the extracellular and transmembrane regions linked to a heterologous cytoplasmic domain were not targeted by Vpu. Thus, sequences present in the cytoplasmic domain of CD4 are necessary and sufficient to confer sensitivity to Vpu.     

Comparison of magnetic resonance volume flow rates, angiography, and carotid Dopplers. Preliminary results

BACKGROUND AND PURPOSE: We compared the results of conventional angiography, carotid Doppler, and magnetic resonance angiography volume flow rates to determine the clinical utility of volume flow rate assessment of blood flow to the anterior circulation in patients with carotid occlusive disease. METHODS: From 11 symptomatic patients, a total of 22 extracranial carotid arteries were studied with all three techniques. The studies were independently read, and regression analysis was used to compare the measurements. RESULTS: Carotid Doppler measurements of the distal extracranial carotid arteries were proportional to the inverse of the extracranial carotid volume flow rate (r = .53, R2 = 29%, P < .01), volume flow rates were proportional to the inverse of measured percent stenosis on angiography (r = .84, R2 = 71%, P < .01), and Dopplers were proportional to angiography (r = .94, R2 = 90%, P < .01). Symptomatic Doppler systolic velocity was significantly higher (P < .002), symptomatic measured stenosis was significantly higher (P < .002), and symptomatic volume flow rate was significantly lower (P < .01) than their respective asymptomatic-side values. These preliminary observations, however, may well change once a large data set, especially one in which more patients with high-grade carotid stenosis are included, is studied. CONCLUSIONS: Assessment of carotid volume flow rates by magnetic resonance angiography quantifies flow reduction secondary to atherosclerotic occlusive disease. The easily obtained flow data add both documentation of arterial flow characteristics related to internal carotid stenosis and information regarding the adequacy of collateral pathways.     

Nonsulfhydryl-reactive phenoxyacetic acids increase aqueous humor outflow facility

PURPOSE: The phenoxyacetic acid, ethacrynic acid (ECA), has potential use in glaucoma therapy because it acts to increase aqueous outflow in vivo and in vitro. In human trabecular meshwork (HTM) cell culture, ECA acts to change cell shape and attachment, effects that have been correlated with microtubule (MT) alterations and chemical sulfhydryl (SH) reactivity. To further explore these actions, we evaluated two non-SH reactive phenoxyacetic acids, inadcrinone and ticrynafen, and the MT-disrupting drug vinblastine. METHODS: Excised bovine and porcine eyes were perfused and outflow facility measured. Calf pulmonary artery endothelial and HTM cells were grown in culture and cytoskeletal effects evaluated after drug treatment. RESULTS: Indacrinone, ticrynafen, and vinblastine all caused an increase in outflow facility. In contrast with ECA, the outflow effects of indacrinone and ticrynafen were not blocked by excess cysteine. Although indacrinone and ticrynafen produced changes in cell shape in vitro, the beta-tubulin staining pattern of treated cells was not altered. Vinblastine caused cell shape change and the expected MT disruption. CONCLUSIONS: Phenoxyacetic acids can increase aqueous outflow facility and alter HTM cell shape and attachment in vitro by a non-SH, non-MT mechanism (which is probably shared also by ECA). These findings suggest the possibility of a broader class of glaucoma drugs that may be directed at the HTM. An understanding of the cellular target for these drugs has implications both for potential glaucoma therapy and for the cytoskeletal mechanisms involved in normal outflow function.     

Application profile for ISDN

The authors examine some key data processing applications to be used in conjunction with the voice and facsimile services as a platform for deploying ISDN (integrated services digital network) in North America. Special emphasis is placed on the emerging standards of both Accredited Standards Committees (ACS) T1 and X3 in an attempt to harmonize the computer and telecommunication industries towards providing the user with an integrated platform that is vendor-transparent and ubiquitous. This generic platform, which spans a large spectrum of businesses, is presented as a base context for defining user-specific needs and incubating the applications that directly relate to businesses. Distributed transaction processing, electronic data interchange, information retrieval, electronic mail, and file transfer together with seven supplementary services for voice and G4 facsimile are proposed for ISDN deployment in the marketplace. The authors describe how the relevant standards may be exercised through the various ISDN channels and emphasize the value of the North American ISDN User's Forum for commercializing this platform     

Deuterated liquid scintillator (NE230) as a fast neutron detectorfor cold-fusion and other research

Deuterated scintillators (NE230) can provide, without time-of-flight, usable neutron energy spectra for neutrons E _n⩾1 MeV. The authors have assembled and calibrated several of these detectors and used them in experiments searching for d+d fusion-neutron emission (E_n, 2.5 MeV) in Pd+D ₂O electrolysis and Ti+D₂ adsorption at LN temperatures. The detectors yielded direct fusion-neutron spectra and set limits in the Pd+D and Ti+D experiments of <7×10^-24 fusion n/s/dd pair and <3×10^-24 fusion n/s/dd pair respectively. In addition, these detectors have been used for in-beam accelerator experiments requiring coincidence between fast neutrons and scattered ions     

Pressurized fluidized-bed hydro retort ing of raw and beneficiated Eastern oil shales

Bench-scale tests were conducted with raw and beneficiated shales in an advanced multi-purpose research reactor. Raw Alabama shale and raw and beneficiated Indiana shales were retorted at 515 °C using hydrogen pressures of 4 and 7 MPa. Shale feed rates were 15 to 34 kg h⁻¹. High oil yields and carbon conversions were achieved in all tests. Oil yield from Alabama shale hydroretorted at 7 MPa was 200% of Fischer assay. Raw and beneficiated Indiana shales hydroretorted at 7 MPa produced oil yields of 170 and 195% of Fischer assay respectively. Total carbon conversions were >70% for all tests conducted at 7 MPa.