Human immunodeficiency virus infection and stroke in young patients

OBJECTIVE: To determine the association between human immunodeficiency virus (HIV) infection and stroke among young persons. DESIGN: Retrospective case-control study. SETTING: Large, inner-city public hospital. PARTICIPANTS: All patients aged 19 to 44 years with a diagnosis of stroke, whose HIV status was determined, admitted from January 1990 through June 1994. Controls matched for age and sex were selected from patients who were admitted during the same period for status asthmaticus whose HIV status was known. MAIN OUTCOME MEASURE: The associations of HIV infection with all strokes and with cerebral infarction, after adjustment for other cerebrovascular risk factors, were evaluated by Mantel-Haenszel stratified analyses. The subtypes and causes of stroke in HIV-infected patients were compared with HIV-seronegative patients. RESULTS: The HIV infection was associated with stroke (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.0-5.3) and cerebral infarction (OR, 3.4; 95% CI, 1.1-8.9), after adjustment for other cerebrovascular risk factors. Among patients with stroke, cerebral infarction was more frequent in HIV-infected patients than in HIV-seronegative patients (20 [80%] of 25 vs 48 [56%] of 88, P = .04). The frequency of cerebral infarctions associated with meningitis (P < .001) and protein S deficiency (P = .06) was higher in HIV-infected patients than in seronegative patients. CONCLUSIONS: Our study suggests that HIV infection is associated with an increased risk of stroke, particularly cerebral infarction in young patients. This risk is probably mediated by increased susceptibility of HIV-infected patients to meningitis and protein S deficiency.     

Epstein-Barr virus uses HLA class II as a cofactor for infection of B lymphocytes

Infection of B lymphocytes by Epstein-Barr virus (EBV) requires attachment of virus via binding of viral glycoprotein gp350 to CD21 on the cell surface. Penetration of the cell membrane additionally involves a complex of three glycoproteins, gH, gL, and gp42. Glycoprotein gp42 binds to HLA-DR. Interference with this interaction with a soluble form of gp42, with a monoclonal antibody (MAb) to gp42, or with a MAb to HLA-DR inhibited virus infection. It was not possible to superinfect cells that failed to express HLA-DR unless expression was restored by transfection or creation of hybrid cell lines with complementing deficiencies in expression of HLA class II. HLA class II molecules thus serve as cofactors for infection of human B cells.     

Relationship between lipoprotein lipase and high density lipoprotein cholesterol in mice: modulation by cholesteryl ester transfer protein and dietary status

Plasma lipoprotein lipase (LPL) activity correlates with high density lipoprotein (HDL) cholesterol levels in humans. However, in several mouse models created either through transgenesis or targeted inactivation of LPL, no significant changes in HDL cholesterol values have been evident. One possible explanation for this species difference could be the absence of plasma cholesteryl ester transfer protein (CETP) activity in mice. To explore this possibility and further investigate interactions between LPL and CETP modulating HDL cholesterol levels in vivo, we examined the relationship between LPL activity and HDL levels in mice expressing the simian CETP transgene, compared with littermates not carrying the CETP gene. On a chow diet, increasing LPL activity was associated with a trend towards increased HDL levels (51 +/- 29 vs. 31 +/- 4 mg/dL highest vs. lowest tertiles of LPL activity, P = 0.07) in mice expressing CETP, while no such effects were seen in the absence of CETP (65 +/- 12 vs. 61 +/- 15 mg/ dL). Furthermore, in the presence of CETP, a significant positive correlation between LPL activity and HDL cholesterol was evident (r = 0.15, P = 0.006), while in the absence of CETP no such correlation was detected (r = 0.15, P = 0.36), highlighting the interactions between LPL and CETP in vivo. When mice were challenged with a high fat, high carbohydrate diet, strong correlations between LPL activity and HDL cholesterol were seen in both the presence (r = 0.45, P = 0.03) and absence (r = 0.73, P < 0.001) of CETP. Therefore, under altered metabolic contexts, such as those induced by dietary challenge, the relation between LPL activity and HDL cholesterol may also become evident. Here we have shown that both genetic and environmental factors may modulate the association between LPL activity and HDL cholesterol, and provide explanations for the absence of any changes in HDL values in mice either transgenic or with targeted disruption of the LPL gene.     

Structural characterization of the maltose acceptor-products synthesized by Leuconostoc mesenteroides NRRL B-1299 dextransucrase

The glucooligosaccharides (GOS), produced by Leuconostoc mesenteroides NRRL B-1299 dextransucrase through an acceptor reaction with maltose and sucrose, were purified by reverse phase chromatography. Logarithmic plots of retention time vs. dp of the GOS gave three parallel lines suggesting the existence of at least three families of homologous molecules. The structure (13C and 1H NMR spectroscopy) and reactivity of the purified molecules of the three families were investigated. All the products bear a maltose residue at the reducing end. The GOS in the first family (named OD) contained additional glucosyl residues all alpha-(1-->6) linked. The smallest molecule in this first series was panose or alpha-D-glucopyranosyl-(1-->6)-D-maltose (dp 3). All the OD molecules were shown to be good acceptors for dextransucrase in the presence of sucrose. The second family, named R, was composed of linear GOS containing alpha-(1-->6)-linked glucosyl residues and a terminal alpha-(1-->2)-linked residue at the non-reducing end of the molecule; the smallest molecule in this family was alpha-D-glucopyranosyl-(1-->2)-D-panose (dp 4). The third family, R', was formed of GOS containing additional residues linked through alpha-(1-->6) linkages that constitute the linear chain, and an alpha-(1-->2)-branched residue located on the penultimate element of the chain, near the non-reducing end. The smallest molecule in this series is alpha-D-glucopyranosyl-(1-->6)-[alpha-D-glucopyranosyl-(1-->2)]-alpha-D- glucopyranosyl-(1-->6)-D-panose, dp 6. R and R' GOS are very poor acceptors for L. mesenteroides NRRL B-1299 dextransucrase. This study makes it possible to suggest a rather simple reaction scheme, where molecules Ri, R'i and ODi of the same dp all result from the glucosylation of the same GOS: ODi-l.     

Facially generated occlusal vertical dimension

Facial height has a profound effect on attractiveness. Occlusal vertical dimension (OVD) determines facial proportion at maximum intercuspation and influences facial dimension at rest. Deficient facial height visibly compromises optimal facial beauty. This article explores the dependent relationships between the OVD and facial esthetics, and discusses the role of facial analysis in determining an optimal OVD.     

Effects of TCDD on Ah receptor, ARNT, EGF, and TGF-alpha expression in embryonic mouse urinary tract

Lipoprotein(a) [Lp(a)] biogenesis was examined in primary cultures of hepatocytes isolated from mice transgenic for both human apolipoprotein(a) [apo(a)] and human apoB. Steady-state and pulse-chase labeling experiments demonstrated that newly synthesized human apo(a) had a prolonged residence time (approximately 60 min) in the endoplasmic reticulum (ER) before maturation and secretion. Apo(a) was inefficiently secreted by the hepatocytes and a large portion of the protein was retained and degraded intracellularly. Apo(a) exhibited a prolonged and complex folding pathway in the ER, which included incorporation of apo(a) into high molecular weight, disulfide-linked aggregates. These folding characteristics could account for long ER residence time and inefficient secretion of apo(a). Mature apo(a) bound via its kringle domains to the hepatocyte cell surface before appearing in the culture medium. Apo(a) could be released from the cell surface by apoB-containing lipoproteins. These studies are consistent with a model in which the efficiency of post-translational processing of apo(a) strongly influences human plasma Lp(a) levels, and suggest that cell surface assembly may be one pathway of human Lp(a) production in vivo. Transgenic mouse hepatocytes thus provide a valuable model system with which to study factors regulating human Lp(a) biogenesis.     

The cytoplasmic membrane is a primary target for the staphylocidal action of thrombin-induced platelet microbicidal protein

Thrombin-induced platelet microbicidal protein (tPMP-1) is a small, cationic peptide released from rabbit platelets exposed to thrombin in vitro. tPMP-1 is microbicidal against a broad spectrum of bloodstream pathogens, including Staphylococcus aureus. Preliminary evidence suggests that tPMP-1 targets and disrupts the staphylococcal cytoplasmic membrane. However, it is not clear if the cytoplasmic membrane is a direct or indirect target of tPMP-1. Therefore, we assessed the in vitro activity of tPMP-1 versus protoplasts prepared from logarithmic-phase (LOG) or stationary-phase (STAT) cells of the genetically related S. aureus strains 19S and 19R (tPMP-1 susceptible and resistant, respectively). Protoplasts exposed to tPMP-1 (2 microg/ml) for 2 h at 37 degrees C were monitored for lysis (decrease in optical density at 420 nm) and ultrastructural alterations (by transmission electron microscopy [TEM]). Exposure to tPMP-1 resulted in substantial lysis of LOG but not STAT protoplasts of 19S, coinciding with protoplast membrane disruption observed by TEM. Thus, it appears that tPMP-1-induced membrane damage is influenced by the bacterial growth phase but is independent of the staphylococcal cell wall. In contrast to 19S, neither LOG nor STAT protoplasts of 19R were lysed by tPMP-1. tPMP-1-induced membrane damage was further characterized with anionic planar lipid bilayers subjected to various trans-negative voltages. tPMP-1 increased conductance across bilayers at -90 mV but not at -30 mV. Once initiated, a reduction in voltage from -90 to -30 mV diminished conductance magnitude but did not eliminate tPMP-1-mediated membrane permeabilization. Therefore, tPMP-1 appears to directly target the staphylococcal cytoplasmic membrane as a primary event in its mechanism of action. Specifically, tPMP-1 likely leads to staphylococcal death, at least in part by permeabilizing the bacterial membrane in a voltage-dependent manner.     

Spontaneous rise of fetal platelet counts despite increasing anti-HPA-5b antibodies

A 47-year-old woman with seronegative polyarthritis, diarrhea, and photosensitivity dermatitis was found to have Crohn's disease and pellagra. The presence of high values of 5-hydroxyindolacetic acid in the urine began the exhaustive investigations and finally enterotomy. No mass lesion was found. Argyrophilic cells were not increased in areas of inflamed intestinal mucosa or the normal mucosa. The disagreement between biochemical and histologic findings was attributed to sampling error. Antiinflammatory treatment for Crohn's disease was given and the gastrointestinal and articular symptoms improved, excretion of 5-hydroxyindolacetic acid returned to normal and there was no relapse of pellagra. Pellagra as a complication of Crohn's disease has been described in 4 cases; malnutrition and intestinal malabsorption were the proposed mechanisms for the niacin deficiency and pellagra of those patients. In the current case, the pathogenesis of pellagra may be accounted to wastage of tryptophan by an increased pool of intestinal argyrophilic cells, suggested by increased urinary excretion of 5-hydroxyindolacetic acid.     

HIV-1 Tat inhibits human natural killer cell function by blocking L-type calcium channels

Herein we show that functional phenylalkylamine-sensitive L-type calcium channels are expressed by human NK cells and are involved in the killing of tumor targets. Blocking of these channels by phenylalkylamine drugs does not affect effector/target cell binding but inhibits the release of serine esterases responsible for cytotoxicity. Interestingly, treatment of NK cells with HIV-1 Tat, which is known to affect several calcium-mediated events in immune cells, impairs their cytotoxic activity. In addition, Tat inhibits the rise in intracellular free calcium concentration upon cross-linking of the adhesion molecule CD11a, engaged during effector/target cell interaction, and the activation molecule CD16. Exogenous Tat does not influence NK-target cell binding but prevents NK cell degranulation. We propose that the molecular structure(s) on NK cells mediating the inhibitory effects HIV-1 Tat belong to L-type calcium channels, based on three lines of evidence: 1) binding of phenylalkylamine derivatives to these channels is cross-inhibited by Tat; 2) L-type calcium channels from NK cell lysates bind to Tat linked to Sepharose columns; 3) the inhibitory effect of HIV-1 Tat on NK cell function is prevented by the agonist of L-type calcium channels, Bay K 8644. Altogether, these results suggest that exogenous Tat is deeply involved in the impairment of NK cell function during HIV-1 infection.