CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5.

For efficient entry into target cells, primary macrophage-tropic and laboratory-adapted human immunodeficiency viruses type 1 (HIV-1) require particular chemokine receptors, CCR-5 and CXCR-4, respectively, as well as the primary receptor CD4 (refs 1-6). Here we show that a complex of gp120, the exterior envelope glycoprotein, of macrophage-tropic primary HIV-1 and soluble CD4 interacts specifically with CCR-5 and inhibits the binding of the natural CCR-5 ligands, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta (refs 7, 8). The apparent affinity of the interaction between gp120 and CCR-5 was dramatically lower in the absence of soluble CD4.

Neurogenic amplification of immune complex inflammation.

The formation of intrapulmonary immune complexes in mice generates a vigorous inflammatory response characterized by microvascular permeability and polymorphonuclear neutrophil influx. Gene-targeted disruption of the substance P receptor (NK-1R) protected the lung from immune complex injury, as did disruption of the C5a anaphylatoxin receptor. Immunoreactive substance P was measurable in fluids lining the lung at time points before neutrophil influx and may thus be involved in an early step in the inflammatory response to immune complexes in the lung.

The C5a chemoattractant receptor mediates mucosal defence to infection.

A family of G-protein-coupled chemoattractant receptors is known to mediate the transport and activation of neutrophils and macrophages This family includes receptors for chemokines, such as interleukin-8, bacterial formylated peptides, platelet-activating factor, leukotriene B4, and the complement anaphylatoxins. The apparent redundancy of these receptors suggests that they have an important underlying role in host defence. To isolate the contribution of particular molecules, we disrupted a gene that encodes a single chemoattractant receptor.

Mutation frequencies of the cytochrome CYP2D6 gene in Parkinson disease patients and in families.

The frequencies of five mutations of the debrisoquine 4-hydroxylase (CYP2D6) gene (mutations D6-A, B, C, D, and T), corresponding to poor metabolizer (PM) phenotypes, were determined by restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR) in 47 patients with Parkinson disease, and compared with the findings in 47 healthy controls. These mutant alleles were about twice as frequent among patients as in controls, with an approximate relative risk ratio of 2.12 (95% confidence interval, 1.

The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates.

We examined the ability of chemokine receptors and related G protein-coupled receptors to facilitate infection by primary, clinical HIV-1 isolates. CCR5, when expressed along with CD4, the HIV-1 receptor, allowed cell lines resistant to most primary HIV-1 isolates to be infected. CCR3 facilitated infection by a more restricted subset of primary viruses, and binding of the CCR3 ligand, eotaxin, inhibited infection by these isolates.

Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils.

The chemokine eotaxin is unusual in that it appears to be a highly specific chemoattractant for eosinophils. Ligand-binding studies with radiolabeled eotaxin demonstrated a receptor on eosinophils distinct from the known chemokine receptors CKR-1 and -2. The distinct eotaxin binding site on human eosinophils also bound RANTES (regulated on activation T expressed and secreted) and monocyte chemotactic protein (MCP)3.

Neutral endopeptidase modulates septic shock.

Neutral endopeptidase (NEP; EC 3.4.24.

Receptor binding specificity and pulmonary gene expression of the neutrophil-activating peptide ENA-78.

Neutrophil-activating peptide ENA-78 is a novel chemotactic cytokine isolated from a human type II pulmonary epithelial cell line. It is a member of the chemokine family of proinflammatory polypeptides and exhibits structural homology to interleukin-8 (IL-8) and GROalpha. The immunohistochemical identification of ENA-78 in pulmonary alveolar leukocytes of bovine pneumonic lungs supports a role for ENA-78 in the pathogenesis of pulmonary inflammation.

Treatment of transverse maxillary deficiency with emphasis on surgically assisted-rapid maxillary expansion.

In this article we discussed the work-up necessary to evaluate a patient for maxillary transverse deficiency, and the three treatments for maxillary transverse deficiency-SDE, RME, and SA-AME. Slow dentoalveolar expansion is used mostly in the primary and early mixed dentition. Rapid maxillary expansion is indicated most often in the mixed dentition and can be attempted in the early adult dentition.

Signaling by hemolytically inactive C5b67, an agonist of polymorphonuclear leukocytes.

The hemolytically inactive complement component complex C5b67, designated iC5b67, can signal human polymorphonuclear leukocytes (PMN) both as a pertussis toxin-inhibitable agonist for chemotaxis and as an antagonist for C5a- and FMLP-stimulated chemotaxis and superoxide production. The signaling pathways utilized by iC5b67 have been further investigated. In contrast to mastoparan, iC5b67 failed to directly activate G proteins to stimulate inositol phosphate formation in COS cells that had been transfected with G alpha 16.

PAf receptor anchors Streptococcus pneumoniae to activated human endothelial cells.

Streptococcus pneumoniae can produce asymptomatic colonization or aggressive sepsis. We sought to differentiate the molecular mechanisms of these disparate courses. Cytokine or thrombin activation of human vascular endothelial cells and type II pneumocytes enhanced pneumococcal adherence relative to resting cells.

Relationships of the 2642 deletion polymorphism (delta 2642) in the huntingtin gene with the CAG repeat expansion length and age at onset of the disease.

The deletion of 3bp at codon positions 2642-2645 (delta 2642) of the gene mutated in Huntington's disease (HD) was analysed on the normal (N) and HD chromosomes of 79 French families affected with HD, and previously typed for the (CAG)n repeats. delta 2642 Polymorphism has been found over-represented on HD chromosomes, the relative risk of HD with the deletion being at a value of 8.26.

Allele doses of apolipoprotein E type epsilon 4 in sporadic late-onset Alzheimer's disease.

Apoliprotein E, type epsilon 4 allele (ApoE-epsilon 4) is associated with late-onset sporadic Alzheimer's disease (AD). We have found that the cumulative probability of remaining unaffected over time decreases for each dose of ApoE-epsilon 4 in sporadic, late-onset French AD. The effect of genotypes on age at onset of AD was analyzed using the product limit method, to compare unaffected groups during aging.

Molecular characterization of two murine eosinophil beta chemokine receptors.

beta or C-C chemokines including RANTES, MCP-3, MIP-1 alpha, and eotaxin have been implicated in the pathogenesis of eosinophilic inflammation. Two human beta chemokine receptors have been cloned and characterized: the MIP-1 alpha/RANTES receptor or C-C chemokine receptor 1 (CCR-1) and the MCP-1 receptor or C-C chemokine receptor 2 (CCR-2). However, no murine beta chemokine receptors have thus far been reported.

Comparison of the structure and expression of the human and rat neprilysin (endopeptidase 24.11)-encoding genes.

The existence of a third non-coding exon in the human neprilysin-encoding gene (h-NEP), positionally located as exon 3, has been demonstrated by reverse transcription of RNA from human kidney and lung, coupled with the polymerase chain reaction. Comparison of nucleotide sequences between h-NEP and the rat NEP (r-NEP) genes shows a high degree of sequence conservation within noncoding exons 1 and 2. In contrast, the region of the gene containing exon 3 is highly divergent.

The role of N-glycosylation for functional expression of the human platelet-activating factor receptor. Glycosylation is required for efficient membrane trafficking.

Streptococcus pneumoniae has been shown to utilize the platelet activating factor receptor for binding and invasion of host cells (Cundell, D. R., Gerard, N.

Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor.

The Gram-positive bacterium Streptococcus pneumoniae is a major cause of pneumonia, sepsis and meningitis. Although the invasive disease is severe, some 40% of individuals harbour the pneumococcus in the nasopharynx asymptomatically. Here we investigate the molecular elements of the encounter between host and pathogen that distinguish these different outcomes.

An unequal cross-over event within the CYP2D gene cluster generates a chimeric CYP2D7/CYP2D6 gene which is associated with the poor metabolizer phenotype.

1. The study of the CYP2D genotype and phenotype of a Caucasian family revealed that a XbaI-9 kb allele was associated with the poor metabolizer phenotype. 2.

Probing the "message:address" sites for chemoattractant binding to the C5a receptor. Mutagenesis of hydrophilic and proline residues within the transmembrane segments.

The C5a anaphylatoxin ligand-receptor interaction on polymorphonuclear granulocytes stimulates chemotaxis, degranulation, and the oxidative burst. The receptor is a member of the large G-protein-coupled family. The ligand is a cationic peptide of 72 amino acids derived from the C5 component of complement and has been shown to have a number of structural requirements for interaction with the receptor.

Residual bodies activate Sertoli cell interleukin-1 alpha (IL-1 alpha) release, which triggers IL-6 production by an autocrine mechanism, through the lipoxygenase pathway.

Interleukin-1 (IL-1) and IL-6 are produced by Sertoli cells. As IL-1 stimulates IL-6 production in some tissues, the cascade of events that results in IL-6 secretion by Sertoli cells was studied. The addition of IL-1 alpha to Sertoli cells resulted in a time-dependent increase in IL-6 secretion.

Neutral endopeptidase modulation of septic shock.

Neutral endopeptidase (NEP; EC. 3.4.

Expression and biologic characterization of the murine chemokine KC.

KC, the product of an immediate early gene induced in mouse fibroblasts by platelet-derived growth factor, was expressed in Escherichia coli by using a maltose binding protein vector and biochemically characterized as a ligand for both murine and human polymorphonuclear neutrophils (PMN). On murine PMN, KC is both a potent chemoattractant and up-regulator of Mac-1 cell surface expression. On human PMN, in contrast, KC exhibits dissociation of its chemoattractant and Mac-1 up-regulatory activities.

Laser arthroscopy of the temporomandibular joint.

Laser surgery is very different than traditional surgery. The clinician must be familiar with the physical properties of the laser to use this instrument safely and properly. Various lasers are available for use in oral and maxillofacial surgery and dentistry, namely the carbon dioxide laser, the neodymium:yttrium-aluminum-garnet laser, and the holmium: yttrium-aluminum-garnet laser (Ho:YAG).