Inhibition of HIV-1 by modification of a host membrane protease

While it is clear that CD4 Is the receptor for the gp120 envelopeprotein of HIV-1, substantial evidence suggests that other hostcell proteins are required for successful membrane fusion. Studieswere initiated to examine the potential for a protein receptorwhich has an elastase-like character to participate in fusionof HIV-1 with permissive host cells. A synthetic elastase inhibitorwas shown to significantly reduce HIV-1 infectivity when presentduring, but not after, the initial contact between virus andcells. A human T cell elastase-like membrane component was purifiedand shown to be lipid-associated. By competitive Inhibition,the purified protein was shown to bind gp160 within the HIV-1fusion domain. The binding parameters of whole T cell membraneextract, with a hydrophobic pentapeptide representative of thefusion domain, suggested an elastase-like protein is the single,secondary T cell receptor for HIV-1 (K = 1x10³ M^–1). Thepentapeptide interacted with porcine and human (epithelial andpolymorphonuclear leukocyte), but not murine, elastase isoforms,suggesting its participation In the permissiveness of host cellsto infection.     

Cytogenetic and comparative genomic hybridization findings in four cases of breast cancer after neoadjuvant chemotherapy

To assess a potential common pattern of genetic alterations in chemotherapy-resistant tumors we analyzed four tumors from breast cancer patients (patients 1-4) after neoadjuvant chemotherapy, by comparative genome hybridization (CGH) and conventional chromosome banding analysis. All patients showed structural aberrations involving chromosomes 1, 5, 11, 16, and 17. In CGH analysis, the patients showed typical imbalances for ductal breast cancer: gains of 1q (3 patients), 5q (2 patients), 8q (3 patients), and X (4 patients) and losses of 1p33 approximately p36 (3 patients), 16q (3 patients), 17p (3 patients), 19 (4 patients), and 22q (4 patients). Other recurrent imbalances of atypical pattern for ductal breast cancer were gain of 4q21 approximately q32 (2 patients), 20q21 approximately q22 (2 patients), and 21 (2 patients) and loss of 20p (3 patients). Three patients showed involvement of several regions bearing genes of drug resistance (MDR1 [HUGO symbol: ABCB1], BCRP [HUGO symbol: ABCG2], MRP1 [HUGO symbol: ABCC1], RFC1); the fourth patient displayed an amplification in the region of MYC (alias c-myc), thus providing--at the level of the light microscope--an explanatory background for the ability of their tumors to survive anthracycline-, taxane- and cyclophosphamide-based chemotherapy. Conventional cytogenetic analysis and CGH displayed highly coincidental findings in the tumors of four patients after neoadjuvant chemotherapy for breast cancer.     

Mechanisms of respiration and phosphorylation in Ascaris muscle mitochondria

In Ascaris muscle mitochondria the major respiratory chain-linked phosphorylation activity is accomplished by a NADH-linked reduction of fumarate to succinate. Oxygen can also be employed as a terminal electron acceptor via a cyanide- and salicyl-hydroxamate-resistant terminal oxidase. As in fumarate-dependent electron transport this process appears to be coupled to energy conservation at phosphorylation site I. The branchpoint from which electrons are taken from the main respiratory chain to either the alternative oxidase or fumarate reductase is likely to be on the oxygen side of the NADH dehydrogenase segment.Malate and succinate are the only substrates which appreciably support respiration in the mitochondrion of the nematode. Regardless of the presence or absence of oxygen malate is utilized by an oxidation-reduction reaction resulting in the formation of pyruvate, acetate, succinate, propionate and CO₂. In addition, aerobically, hydrogen peroxide is formed as the product of oxygen reduction. Succinate accumulation was found to be significantly higher in the anaerobic as compared to the aerobic incubation mixtures. This effect was accompanied by an increase in anaerobic malate consumption. ATP generation and the formation of pyruvate, acetate and propionate were found to be similar in the presence and absence of oxygen.In malate-supported respiration of intact Ascaris mitochondria reducing equivalents (NADH) are produced exclusively through pyruvate and acetate formation. These enzymatic reactions are functionally coupled to the electron transport-linked reductions of fumarate to succinate and oxygen to hydrogen peroxide, respectively. In accordance with the position of the redox potentials of the fumarate/succinate and O₂/H₂O₂ couples, anaerobic and aerobic respiration was found to be associated with relatively low energy conservation efficiencies. Thus one molecule of ATP was conserved per 2e^? transferred to fumarate or oxygen, respectively. No evidence could be obtained for a significant activity of energy conservation sites II and III and electron transfer through the alternative oxidase pathway was shown not to be coupled to phosphorylation.     

Effect of surface treatment on the shear bond strength of three resin cements to a machinable feldspatic ceramic

The aim of this study was to evaluate the shear bond strength of three resin cements to Vita Mark II ceramics under different pretreatments of the ceramic surface and to examine whether simplified pretreatment procedures would result in satisfying results compared to the state of the art. RelyX Unicem (RXU), Calibra (CAL), and Variolink II (VAR) were used as resin cements and bonded to machine milled feldspatic disks, pretreated in five different ways. (1) no pretreatment of the ceramic surface; (2) surface etched with hydrofluoric acid (HF); (3) ceramic surface silanized; (4) ceramic surface etched (HF) and silanized, (5) ceramic surface etched (HF), silanized, and covered with Heliobond. The shear bond strengths were measured initially, after 5000 and 10,000 thermocycles (TC). After 10,000 TC for CAL only procedure 5 resulted in a reliable adhesion median value of 10.7 MPa. VAR showed median values of 24.6, 17.2, and 18.1 MPa for pretreatments 5, 3, and 4, respectively. RXU performed 25.9, 22.0, and 11.0 MPa for procedures 5, 4, and 3, respectively. For procedure 2, RXU revealed the significantly highest value with 15.4 MPa (U-test, p = 0.05). Only RXU-luted specimens of procedure 1 survived the 10,000 thermocycles. The results revealed that a simplification of the ceramic pretreatment for VAR and RXU might be possible.     

Separate and variably shaped chromosome arm domains are disclosed by chromosome arm painting in human cell nuclei

Fluorescence in situ hybridization (FISH) with microdissection probes from human chromosomes 3 and 6 was applied to visualize arm and subregional band domains in human amniotic fluid cell nuclei. Confocal laser scanning microscopy and quantitative three-dimensional image analysis showed a pronounced variability of p- and q-arm domain arrangements and shapes. Apparent intermingling of neighbouring arm domains was limited to the domain surface. Three-dimensional distance measurements with pter and qter probes supported a high variability of chromosome territory folding.     

Pontine veins. MRI cross-sectional anatomy

Summary The pons is covered by a rich venous network offering numerous vascular landmarks in MRI and during surgery. We present an original study of the veins as they appear on MR multiplanar scans after gadolinium IV injection. This prospective study is based on 40 consecutive patients with normal posterior fossa structures. One of the major venous collectors follows the pons: the superior petrosal v. was identified on MRI in 95% of our cases. Its hooklike extremity drains into the superior petrosal sinus. The inferior petrosal v. was never identifiable. The superficial pontine venous network are identified in 72.5% of cases in the axial plane and were organised in longitudinal and transverse collectors, whose MR aspects are presented here.

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Les veines du pont. Anatomie sectionnelle en IRM

Résumé Le pont, enveloppé des citernes subarachnoïdiennes, est parcouru à sa surface par de nombreux vaisseaux qui constituent autant de points de repère topographiques en IRM que de rapports chirurgicaux. Nous présentons une étude de l'anatomie veineuse en coupe telle que l'IRM la révèle après injection de Gadolinium. Cette étude prospective comporte 40 patients indemmes de lésion de la fosse crânienne postérieure. Le pont est longé par un des collecteurs majeurs du tronc cérébral : la v. pétreuse supérieure, identifiée dans 95 % des cas. Elle se jette par un crochet caractéristique dans le sinus pétreux supérieur. La v. pétreuse inférieure n'a jamais été reconnue. Les vv. pontiques forment un réseau maillé visible dans 72,5 % des cas en coupes axiales et comportant des axes transversaux et longitudinaux dont les critères d'identification sont présentés selon le plan de coupe.

     

Evaluation of a computerized appointment system in general practice.

Computers have gained rapid acceptance in general practice. A recent development has been the use of computers to run practice appointment systems. This study demonstrates the benefits of installing a computerized appointment system, with improved service for patients, and more efficient use of time by both doctors and receptionists.     

Influences of Subject Self-Selection on the EEG Alpha-Hypnotizability Correlation

To determine the effect of subject self-selection on the alpha-hypnotizability correlation, the correlations between volunteer and invited subject groups were compared. For 8 volunteers the correlation between baseline eyes-closed occipital alpha and the Harvard Group Scale of Hypnotic Susceptibility score was r=.72; for 12 invited subjects, that correlation was r=-.02. The significant difference in these correlations gives support to a previously published paper which hypothesized, on the basis of a literature review, that sampling modifications generated by subject self-selection were responsible for the occurrence of significant alpha-hypnotizability correlations.