Respiratory syncytial virus glycoproteins

The proteins of respiratory syncytial (RS) virus were analyzed by SDS-polyacrylamide gel electrophoresis. Eight virion structural proteins with molecular weights of 180,000, 89,000, 48,000, 42,000, 34,000, 28,000, 25,000, and 21,000 were identified. These proteins were given tentative designations of L (180,000), G (89,000), F1 (48,000), NP (42,000), P (34,000), M (28,000), Vp25 (25,000), and F2 (21,000). The 89,000-, 48,000-, and 21,000-dalton polypeptides were glycosylated and could be purified on lentil-lectin sepharose columns. All three glycoproteins could be immunoprecipitated from extracts of infected cells but not from uninfected cells, suggesting that they are viral specified. The host cell affected the apparent molecular weights of the largest and smallest glycosylated polypeptides possibly by differences in glycosylation. The 48,000- and 21,000-dalton glycopolypeptides were disulfide linked subunits of a 68,000-dalton glycoprotein that was seen on unreduced gels. The 68,000-dalton glycoprotein was thus similar to the fusion (F) protein of paramyxoviruses. Treatment of infected cultures with tunicamycin, a drug that blocks glycosylation, inhibited syncytial formation and resulted in over a 1000-fold reduction of extracellular infectious virus. Virions purified from tunicamycin-treated cells had reduced amounts of all three glycosylated proteins. No new forms of these proteins were conclusively identified, suggesting that unglycosylated forms of RS glycoproteins were not incorporated into virion membranes.     

TGF-β2 and PGE2 in Rabbit Blastocoelic Fluid Can Modulate GM-CSF Production by Human Lymphocytes

PROBLEM: During normal pregnancy, major changes occur in the production of Th2/Th1 cytokines at the feto-maternal interface. Th2 cytokines such as interleukin-4 (IL-4) or interleukin-10 (IL-10) are predominantly produced locally in the uterine and placental tissues, whereas the production of Th1 cytokines such as tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) are decreased. Because these modulations might be induced by the embryo, the current study was carried out to test the effect of rabbit blastocoelic fluid on the production of Th2/Th1 cytokines by lymphocytes, and to investiate the possible implication of transforming growth factor β₂ (TGF-β₂) prostaglandin E₂ (PGE₂) as modulators of the production of these cytokines. METHOD OF STUDY: Human peripheral blood lymphocytes (PBL) were cultured along with ConcanavalinA (Con A), and rabbit blastocoelic fluid was collected on day 12 of gestation (BF d-12). Concentrations of cytokines in culture media were determined by enzyme-linked immunoadsorbent assay (ELISA). RESULTS: Addition of BF d-12 in the culture medium induced a strong inhibition of IL-2, TNF-α, IL-10, and granulocyte-macrophage colony-stimulating factor (GM-CSF) production. However, an initial pretreatment of the lymphocytes with BF d-12, followed by a Con A stimulation, led to a marked increase in GM-CSF production, whereas IL-2, TNF-α, and IL-10 secretions were inhibited. It was also demonstrated, for the first time, that a pretreatment of the lymphocytes with TGF-β₂ and PGE₂ increased GM-CSF production to the same level reached after the addition of BF d-12. Furthermore, removal of TGF-β₂ and PGE₂ from BF d-12 by affinity chromatography reduced the effect of BF d-12 on GM-CSF production. CONCLUSIONS: Taken together, these findings suggest that the embryo, in modulating harmful and beneficial cytokine production locally, plays an active role in its protection against maternal immune cellular assault. These results also emphasize the importance of growth factors for successfully maintaining pregnancy.     

Urban adolescents' perceptions of their neighborhoods: An examination of spatial dependence

Spatial dependence exists when the variation between observations is dependent on spatial location. In the present study, geostatistical methods were used to examine spatial dependence in adolescents' perceptions of their neighborhoods: whether adolescents living in close proximity perceived their neighborhoods more similarly than adolescents living further apart. Participants included 343 adolescents (53% male; 91% African American) enrolled in sixth grade, residing in Baltimore City, with geocoded home addresses. These addresses were used in combination with a measure of perceived neighborhood disorder and disadvantage to compute variogram plots, a geostatistical technique used to evaluate spatial dependence. Results indicated that perceptions of youth residing in close geographic proximity were more similar than perceptions of youth residing further apart. Adjusting for census‐level characteristics, but not individual and family characteristics, resulted in decreased variation among participants but did not eliminate the spatial dependence. Findings highlight the utility of geostatistical methods for social science research. © 2004 Wiley Periodicals, Inc. J Comm Psychol 32: 277–293, 2004.     

Characterization of host CD4+ T lymphocytes in mice neonatally tolerized to alloantigens

BALB/c mice injected at birth with semi-allogeneic F1 spleen cells become tolerant to alloantigens as shown by their CTL unresponsiveness to the corresponding alloantigen and the persistence of donor F1 cells into the BALB/c host. Moreover, these mice develop a transient systemic lupus erythematosis-like autoimmune syndrome characterized by splenomegaly, glomerulonephritis, thrombocytopenia and abnormal serological findings, such as several autoantibodies and IgG1 hypergammaglobulinemia. Recent studies done in our laboratory have shown that donor F1 B cells persisting in the host are responsible for the production of autoantibodies and must be activated in vivo by the host CD4⁺ T lymphocytes in a MHC class II-restricted fashion. In the present work, we have focused our attention on the ability of splenic CD4⁺ T cells recovered at different periods from BALB/c mice injected at birth with (CBA/Ca × BALB. Igh^b) Fl spleen cells to interact with and activate F1 semi-allogeneic spleen cells in vitro. We show that (i) only CD4⁺ T cells from 2- and 3-week-old tolerant BALB/c mice preferentially produce IL-4 and IL-5 in response to a F1 semi-allogeneic in vitro stimulation, (ii) CD4⁺ T cells purified from 3-week-old tolerant BALB/c mice are able to induce in vitro IgG and IgM production by F1 B cells. Taken together, these results strongly suggest that host CD4+ T cells, belonging to the TH2 subset progressively lose their reactivity towards the F1 semi-allogeneic persistent B cells, reaching a state of unresponsiveness that correlates with the disappearance of serum autoantibodies and autoimmune pathology.     

A polymorphism in the angiotensin 1-converting enzyme gene is associated with damage to cerebral cortical white matter in Alzheimer's disease

The impact of the insertion (I)/deletion (D) (I/D) polymorphism in the angiotensin 1-converting enzyme (ACE) gene on the extent of white matter myelin loss (ML) was investigated in four regions of the cerebral cortex in an autopsy-confirmed series of 93 patients with Alzheimer's disease (AD). The possible influence of APO E epsilon4 allele acting in concert with ACE D allele was assessed. The extent of ML did not differ between D/D, I/D and I/I genotype groups when data from all four brain regions were combined. However, separate analysis showed that the frontal and temporal cortex tended to be affected more severely by ML in patients with D/D genotype compared to those with I/D and I/I genotypes. Stratification according to APO E epsilon4 allele revealed a greater overall ML in patients bearing at least one copy of ACE D allele and one APO E epsilon4 allele, especially in individuals homozygous for both. The APO E epsilon4 allele may therefore act synergistically in patients with AD (and other subjects) bearing ACE D/D genotype to increase the risk of ML, perhaps through transient ischaemic episodes consequent upon poor cardiac output associated with coronary atherosclerosis in patients with the APO E epsilon4 allele.     

No persistent effect of preweaning nutrition on postweaning food intake, feeding efficiency, or body energy stores in Long-Evans rats.

The purpose of this study was to determine the relative importance of pre- and postweaning nutrition on body mass, body fat, and feeding efficiency in Long-Evans rats up to a period of 18 weeks following weaning. Female rats were bred and pups were redistributed to form large (14-19 pups), normal (11-13 pups) and small (4 pups) litter groups. Weaned rats were housed as pairs (40 pairs) or singletons (n = 16) and fed either a mixed-fat diet (36.6% fat) or a standard chow diet (13.5% fat). Food intake, body mass, and feeding efficiency were measured at 4, 8, 12, and 18 weeks postweaning. Total body fat and depot fat pad mass were also measured at 18 weeks postweaning. At weaning, pups from small litters were fatter (p less than 0.001), and had a greater mass (p less than 0.03) than pups from large litters. There were no persistent effects of preweaning litter size after covarying for preweaning mass on body mass, and postweaning growth, food intake, feeding efficiency, or body fat accretion. Male rats ingesting the mixed-fat diet had a greater body mass (p less than 0.05), greater body fat accretion (p less than 0.008) and a higher feeding efficiency (p less than 0.001) than their chow-fed counterparts, despite an overall lower energy intake (p less than 0.05). Female rats ingesting the mixed-fat diet had a lower food energy intake (p less than 0.005) and a greater feeding efficiency (p less than 0.001) than chow-fed rats during the early postweaning period, only. Thus, postweaning nutrition may play a more important role in postweaning adult mass and depot fat in freely eating rats than early nutritional experiences.     

Branchial dysplasia, mental deficiency, club feet, and inguinal herniae: a report of two further cases associated with paucity of interlobular bile ducts.

The observation of two new cases in a previously reported family has brought about a change in the delineation of the syndrome initially defined. To the abnormalities already described (branchial dysplasia, mental deficiency, club feet, inguinal herniae) must be added a paucity of interlobular bile duts; the relationship between this new syndrome and the Alagille syndrome requires reconsideration.     

Three-dimensional modeling of the anatomy of the heart and great vessels

Summary The anatomic constraints imposed on a total artificial heart (TAH) require specific anatomic studies. A thoracic anatomic study was performed with a scanning device equipped with three-dimensional (3-D) reconstruction software on 15 male patients, between the ages of 41 to 63 years (52 ± 6 years). All were candidates for heart transplantation. The 3-D reconstructions of the cardiovascular structures obtained from surgical anatomy data specific to TAH implantation allowed a volumetric measurement of these structures. A modeling diagram of these structures permitted reproducible quantitative measurements of the 35 geometrical parameters which characterized shape, orientation, and position of these structures within the thorax. Most of the measured parameters were characterized by low variability (coefficient of variation from 10 to 25%).

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Modélisation tridimensionnelle de l'anatomie du cur et des gros vaisseaux

Résumé Les contraintes anatomiques imposées au cur artificiel total (CAT) nécessitent des études anatomiques spécifiques. Une étude anatomique thoracique a été réalisée avec un scanner doté d'un logiciel de reconstruction tridimensionnelle (3-D) chez 15 patients, tous de sexe masculin, agés de 41 à 63 ans (52 ± 6 ans), et candidats à une transplantation cardiaque. Les reconstructions 3-D des structures cardio-vasculaires réalisées selon les données de l'anatomie chirurgicale propre à l'implantation du CAT ont permis la mesure volumétrique de ces structures. Un schéma de modélisation de ces structures a permis des mesures quantitatives reproductibles de 35 paramètres géométriques caractéristiques de la forme, de l'orientation, de la position de ces structures dans le thorax. Les résultats de ces mesures ont pu être exprimés en termes statistiques. La plupart des paramètres mesurés étaient caractérisés par une faible variabilité (coefficients de variations de 10 à 25%).

     

Persistent Cytomegalovirus infection—The etiology of Sjogren's Syndrome

The persistence of Cytomegalovirus (CMV) with alteration of cell surface expression in certain tissues may initiate the tissue destruction that leads to the clinical manifestations of Sjogren's Syndrome. Salivary gland and lacrimal gland ductal cells are immunologically attacked due to CMV antigenic expression. The destruction of these ducts leads to xerostomia and keratonconjunctivitis sicca, the hallmarks of Sjogren's Syndrome.     

T cell receptor gene in synovial tissues of rheumatoid arthritis

Rheumatoid arthritis is a chronic and destructive autoimmune joint disease characterized by inflammation of synovial tissue of unknown aetiology. Studies on TCR genes expressed by infiltrating T cells in synovial tissues have attempted to identify mechanism and specificity of the recruitment. T cell infiltrate in rheumatoid arthritis appears to be an association of a polyclonal non specific infiltrate with dominant clones or clonotypes. T cell repertoire in synovial tissue is biased compared to peripheral blood but no TCR V gene can be identified as commonly over-used. Comparison of motifs found in the CDR3 region of dominant clones from different studies has currently failed to identified a commonly motif. The fact that a number of dominant clones or clonotypes is present in different joints and at different times of the disease suggests a selective expansion of T lymphocytes in rheumatoid arthritis synovial membrane. Further investigations are needed to characterize the specificity of these dominant clonotypes.