Relationship between dynamic balance and self-reported handicap in patients who have unilateral peripheral vestibular loss.

OBJECTIVE: The purpose of this study was to investigate whether Dizziness Handicap Inventory (DHI) score is related to postural performance as assessed by dynamic posturography. STUDY DESIGN: Retrospective study. SETTING: Outpatient in a tertiary referral center. PATIENTS: Ninety-two complete unilateral vestibular loss patients, categorized into 3 groups according to the postlesion stage: 1 to 2 months (n = 32; age, 47.6 +/- 10.7 yr), 4 to 7 months (n= 23; 47.1 +/- 8.37 yr), and 1 year and older (n = 37; 49.2 +/- 9.5 yr). MAIN OUTCOME MEASURES: Dizziness Handicap Inventory and dynamic balance measured with a seesaw platform moving either in the anterior-posterior or in the mediolateral direction. RESULTS: The mean DHI score was 25.8 +/- 18.7 and the range was 0 to 68. Dizziness Handicap Inventory scores did not differ significantly between the different unilateral vestibular loss groups studied. No difference was detected between the groups for the 3 subscores (emotional, functional, and physical), except that the older-than-1-year group had a significantly higher physical score than the 2 others. No correlation was found between DHI scores and postural indicators for either direction of the platform. However, patients unable to maintain balance when the seesaw platform moved in the mediolateral direction had significantly higher DHI scores than those who did not fall. CONCLUSION: Even if they are not directly related, we suggest that DHI and dynamic posturography are complementary approaches for appreciating the vestibular compensation process and are thus useful for postoperative counseling for vestibular loss patients.     

Vasopressin receptors in the mouse (Mus musculus) brain: sex-related expression in the medial preoptic area and hypothalamus

We have investigated the distribution of vasopressin binding sites in the brain of male and female adult mice using a radio-iodinated ligand and film autoradiography. Vasopressin receptors were uncovered in various regions of the brain including the basal nucleus of Meynert, the substantia innominata, the hypothalamic paraventricular nucleus, the substantia nigra pars compacta and the hypoglossal nucleus. A sex-related difference in the expression of vasopressin receptors was seen in the medial preoptic area/anterior hypothalamus corresponding to the rat sexually dimorphic nucleus in the rat and in the hypothalamic mammillary nuclei. In both structures the autoradiographic labeling is more intense in females than in males. These observations confirm that vasopressin binding sites are present in the hypothalamic preoptic area of most species examined so far and that sex-related expression of neuropeptide receptors could trigger sex-related behavioral differences.     

Kinetic and biologic properties of recombinant ChIFN-gamma expressed via CELO-virus vector.

In this study, a replicative fowl adenovirus serotype 1 (CELO) recombinant expressing chicken interferon-gamma (ChIFN-gamma) was constructed. In the engineered recombinant, the ChIFN-gamma gene was placed under the control of cytomegalovirus (CMV) promoter. The ChIFN-gamma expression cassette was inserted in the right end of the CELO genome (D fragment), which was able to carry the largest insertion of foreign DNA without affecting the replication functions of the vector. The recombinant ChIFN-gamma (rChIFN-gamma) produced in the CELO-virus expression system was characterized by comparing its biologic activities with that of rChIFN-gamma produced via the baculovirus expression system (Bac-ChIFN-gamma). CELO-ChIFN-gamma inhibited the replication of cytolytic virus in chicken embryo fibroblasts (CEFs) and activated macrophages in a better manner than did Bac-ChIFN-gamma . Moreover, the in vitro and in vivo stability of the CELO-derived rChIFN-gamma was considerably higher than that of the Bac-ChIFN-gamma. The CELO-ChIFN-gamma recombinant vector was able to replicate in vitro in the loghorn male hepatoma (LMH) hepatocyte cell line and to produce detectable levels of recombinant cytokine in supernatant as early as 90 min post-infection. Therefore, the CELO-virus expression system is an appropriate system for high-level expression of biologically active and stable ChIFN-gamma.     

Impaired responses to toll-like receptor 4 and toll-like receptor 3 ligands in human cord blood

Toll-like receptor (TLR)-4 signaling pathway plays an essential role in host defense against gram-negative bacteria while TLR-3-mediated signaling is critically involved in anti-viral immunity. To gain insight into the defects responsible for impaired Th1 responses in human newborns, we investigated the responses of human cord blood cells to lipopolysaccharide, LPS, and to polyinosinic-polycytidylic acid, Poly (I:C), ligands of TLR-4 and TLR-3, respectively. Measurement of cytokine levels revealed a profound defect in IL-12 (p70) synthesis and an increased release of IL-10 in cord blood exposed to LPS or Poly (I:C), as compared to adult blood. Moreover, Poly (I:C)-induced IFN-alpha production was found to be significantly impaired in cord blood. Phenotypic maturation of myeloid DC in response to LPS or Poly (I:C) was next compared in cord and adult blood. We observed that neonatal myeloid DC displayed decreased upregulation of CD40, CD80 whereas CD86 and HLA-DR upregulation did not differ significantly between adults and neonates. Taken together, these findings might be relevant to the increased vulnerability of human newborns to intracellular pathogens and to their inability to develop efficient Th1-type responses.     

Pre-B-cell colony-enhancing factor,whose expression is up-regulated in activated lymphocytes,is a nicotinamide phosphoribosyltransferase,a cytosolic enzyme involved in NAD biosynthesis

The murine homologue of the previously identified human "pre-B-cell colony-enhancing factor" (PBEF) gene coding for a putative cytokine has been identified by screening a subtractive library enriched in genes expressed in activated T lymphocytes. Unlike most cytokine genes known to date, the PBEF gene is ubiquitously expressed in lymphoid and non-lymphoid tissues and displays significant homology with genes from primitive metazoans (marine sponges) and prokaryotic organisms. Recently, a bacterial protein encoded by nadV, a gene from the prokaryote Haemophilus ducreyi displaying significant homology with PBEF, has been identified as a nicotinamide phosphoribosyltranferase (NAmPRTase), an enzyme involved in nicotinamide adenine dinucleotide (NAD) biosynthesis. Using a panel of antibodies to murine PBEF, we demonstrate in this work that, similarly to its microbial counterpart, the murine protein is a NAmPRTase, catalyzing the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. The role of PBEF as a NAmPRTase was further confirmed by showing that the mouse gene was able to confer the ability to grow in the absence of NAD to a NAmPRTase-defective bacterial strain. The present findings are in keeping with the ubiquitous nature of this protein, and indicate that NAD biosynthesis may play an important role in lymphocyte activation.     

Lymphotoxin but not tumor necrosis factor functions to maintain splenic architecture and humoral responsiveness in adult mice

To compare the function of the tumor necrosis factor (TNF) and lymphotoxin (LT)α/β systems in the mature immune system, these two pathways were blocked with soluble receptor-immunoglobulin (R-Ig) fusion proteins in normal adult mice. Inhibition of LTα/β signaling using LTβR-Ig or a blocking monoclonal antibody against murine LTβ had profound effects. The spleen lacked discrete B cell follicles and the marginal zone was altered. Less marked changes were detected in lymph nodes. LTα/β inhibition also prevented germinal center formation in the spleen and impaired Ig production in response to sheep red blood cells (SRBC) immunization. These results show that the LTα/β system is required for the maintenance of splenic architecture and normal immune responses, and not simply for the development of peripheral immune organs during ontogeny. In contrast, inhibition of the TNF/LTα pathway with TNF-R55-Ig did not affect the splenic architecture or the anti-SRBC response. Splenic defects and impaired antibody responses are seen in TNF-deficient mice, suggesting that TNF is important during development. Therefore relative to TNF, the LT system has the dominant influence on splenic organization and anti-SRBC Ig formation in the adult mouse.     

Evaluation of Hemagglutinin Protein-Specific Immunoglobulin M for Diagnosis of Measles by an Enzyme-Linked Immunosorbent Assay Based on Recombinant Protein Produced in a High-Efficiency Mammalian Expression System

Recombinant hemagglutinin (H) of the measles virus (MV) expressed in a mammalian high-expression system based on the Semliki Forest virus replicon was used in an enzyme-linked immunosorbent assay (ELISA) for the detection of specific immunoglobulin M (IgM) and IgG in patients with acute-phase measles. One hundred twelve serum specimens from 70 patients with measles were analyzed. Case definition was based on a commercial IgM ELISA that utilizes MV-infected cells (MV-ELISA) (Enzygnost; Behring Diagnostics); the clinical criteria of the Centers for Disease Control and Prevention (Atlanta, Ga.); and/or the increase in hemagglutinin test titers, neutralization test titers, and levels of MV-specific IgG whenever paired sera were available. The initial time courses of the IgM signal after the onset of rash are similar in the H- and MV-ELISAs. On days 0 to 19, both ELISAs detected IgM in 67 of 68 (98.5%) sera. Average maximal levels of IgM seem to persist, however, about 10 days longer in the MV-ELISA (up to day 25) than in the H-ELISA (day 15). From days 20 to 29 and 30 to 59, the H-ELISA detected only 64.3 (9 of 14) and 19.2% (5 of 26), respectively, of sera that were IgM positive by MV-ELISA. At least up to day 30, the performance of the H-ELISA seemed to be similar to that reported for commercial ELISAs based on whole MV. Our results demonstrate that MV H-specific IgM can be used to diagnose most measles cases from a single serum specimen collected within 19 days after the onset of rash and that the recombinant protein used in this study is suitable for this purpose.     

Human immunodeficiency virus 1 favors the persistence of infection by activating macrophages through TNF

Macrophages play a major role in HIV-1 persistence. In the present paper, we demonstrate that the absence of apoptosis in HIV-1-infected primary human monocyte-differentiated macrophages (MDM) correlates with an increase in anti-apoptotic (Bcl-2 and Bcl-x(L)) and a decrease in pro-apoptotic (Bax and Bad) proteins. This is associated with macrophage activation as shown by tumor necrosis factor (TNF) production and NF-kappaB activation upon infection. TNF production was shown to be involved in the upregulation of Bcl-2 and Bcl-x(L) because this increase was abolished by an anti-TNF anti-serum or an inhibitor of TNF synthesis. In parallel, inhibition of TNF production induced an increase in the number of apoptotic cells. Furthermore, using an inhibitor of NF-kappaB activation, we demonstrated that TNF-induced upregulation of Bcl-x(L) and Bcl-2 occurs, respectively, through a NF-kappaB-dependent and an NF-kappaB-independent pathway.     

IgE-mediated anaphylaxis caused by bites of the pigeon tick Argas reflexus: cloning and expression of the major allergen Arg r 1

BACKGROUND: Anaphylactic reactions caused by bites of the European pigeon tick Argas reflexus are repeatedly reported. This soft-backed tick is a parasite of wild pigeons colonizing urban buildings and houses. Occasionally the ticks can bite human beings, inducing anaphylactic reactions in sensitized patients. OBJECTIVE: Our aim was to characterize the major allergen implicated in a series of anaphylactic reactions caused by Argas bites and to produce the allergen as recombinant protein for diagnostic purposes. METHODS: Protein extracts were prepared from whole A reflexus bodies, and IgE immunoblots were performed with sera from 13 patients who had an anaphylactic reaction with pigeon tick bites. A cDNA expression library was constructed from whole ticks and screened with a polyclonal rabbit antiserum raised against the major allergen. RESULTS: The cDNA coding for the dominant allergen Arg r 1 could be isolated. It encodes a protein belonging to the lipocalin family. Allergenicity of the recombinant Arg r 1 was confirmed by immunoblot, ELISA, and intradermal skin tests. CONCLUSION: The dominant allergen of A reflexus has been isolated and the corresponding cDNA cloned. The recombinant protein, a lipocalin, was expressed in Escherichia coli and was shown to be immunoreactive in vitro and in vivo. Recombinant Arg r 1 was used as a diagnostic tool in a series of anaphylactic reactions caused by pigeon tick bites.