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Biomedical subjects

J Lewis

Publications and source records attributed to J Lewis.

At least 73 records · Page 4Linked to original sources

Antigenic variation within the CD4 binding site of human immunodeficiency virus type 1 gp120: effects on chemokine receptor utilization.

To assess the antigenicity of envelope glycoproteins derived from primary human immunodeficiency virus type 1 populations, their interactions with the receptor CD4, and their coreceptor usage, we have cloned and expressed multiple gp120 proteins from a number of primary virus isolates. Characterization of these proteins showed a high degree of antigenic polymorphism both within the CD4 binding site and in defined neutralization epitopes, which may partially account for the general resistance of primary isolates to neutralizing agents. Furthermore, chimeric viruses expressing gp120 proteins with reduced CD4 binding abilities are viable, suggesting that primary viruses may require a less avid interaction with the receptor CD4 to initiate infection than do their laboratory-adapted counterparts. The coreceptor usage of chimeric viruses was related to the ability of the virus to bind CD4, with reduced CD4 binding correlating with preferential usage of CXCR4. Changes in coreceptor usage mapped to sequence changes in the C2 and V4 regions, with no changes seen in the V3 region.

Amino Acid Sequence↗

Molecular cloning of ILP-2, a novel member of the inhibitor of apoptosis protein family.

Inhibitor of apoptosis protein (IAP)-like protein-1 (ILP-1) (also known as X-linked IAP [XIAP] and mammalian IAP homolog A [MIHA]) is a potent inhibitor of apoptosis and exerts its effects, at least in part, by the direct association with and inhibition of specific caspases. Here, we describe the molecular cloning and characterization of a human gene related to ILP-1, termed ILP-2. Despite high homology to ILP-1, ILP-2 is encoded by a distinct gene, which in normal tissues is expressed solely in testis. In contrast to ILP-1, overexpression of ILP-2 had no protective effect on apoptosis mediated by Fas (also known as CD95) or tumor necrosis factor. However, ILP-2 potently inhibited apoptosis induced by overexpression of Bax or by coexpression of caspase 9 with Apaf-1, and preincubation of cytosolic extracts with ILP-2 abrogated caspase activation in vitro. A processed form of caspase 9 could be coprecipitated with ILP-2 from cells, suggesting a physical interaction between ILP-2 and caspase 9. Thus, ILP-2 is a novel IAP family member with restricted specificity for caspase 9.

Amino Acid Sequence↗

Mechanical ventilation of isolated septic rat lungs: effects on surfactant and inflammatory cytokines.

The effects of mechanical ventilation (MV) on the surfactant system and cytokine secretion were studied in isolated septic rat lungs. At 23 h after sham surgery or induction of sepsis by cecal ligation and perforation (CLP), lungs were excised and randomized to one of three groups: 1) a nonventilated group, 2) a group subjected to 1 h of noninjurious MV (tidal volume = 10 ml/kg, positive end-expiratory pressure = 3 cmH(2)O), or 3) a group subjected to 1 h of injurious MV (tidal volume = 20 ml/kg, positive end-expiratory pressure = 0 cmH(2)O). Nonventilated sham and CLP lungs had similar compliance, normal lung morphology, surfactant, and cytokine concentrations. Injurious ventilation decreased compliance, altered surfactant, increased cytokines, and induced morphological changes compared with nonventilation in sham and CLP lungs. In these lungs, the surfactant system was similar in sham and CLP lungs; however, tumor necrosis factor-alpha and interleukin-6 levels were significantly higher in CLP lungs. We conclude that injurious ventilation altered surfactant independent of sepsis and that the CLP lungs were predisposed to the secretion of larger amounts of cytokines because of ventilation.

Animals↗

Start right-eat right award scheme: implementing food and nutrition policy in child care centers.

The Start Right-Eat Right award scheme implemented in Western Australia has been used to provide the incentive to bring about improvement in food service in line with government policy and regulations in the child care industry. Theories of organizational change were used to identify processes and strategies to support the industry in translating policy into practice. A baseline survey of food service management practices, as well as process evaluation, informed action and identified barriers. Impact evaluation demonstrated that the award scheme could bring about improvements in the quality of food service; 80% of centers made changes to their menus as a result of participating. Two years postlaunch, 40% of centers have registered in the scheme. The diffusion of innovation theory is used to explain uptake and discuss results. The success of the scheme was based on four factors: an understanding of the industry, collaboration between the child care industry and government, supporting resources, and incentives.

Certification↗

Sertralilne, paroxetine and venlafaxine in refugee post traumatic stress disorder with depression symptoms.

The authors describe the use of three new antidepressants: Sertralilne, Paroxetine and Venlafaxine in treating Posttraumatic Stress Disorder and symptoms of Depression in adult Bosnian refugees victims of ethnic cleansing. 32 Bosnian refugees with PTSD and symptoms of Depression presenting for treatment of the mental health consequences of surviving ethnic cleansing, participated in a case series study. All subjects completed open trials of Sertraline (15), Paroxetine (12) or Venlafaxine (5), with standard clinical doses. Overall, Sertraline and Paroxetine yielded statistically significant improvement at 6 weeks in the total PTSD symptom severity, in each symptom cluster, in Beck Depression Inventory and in Global Assessment of Functioning. Venlafaxine produced statistically significant improvement at 6 weeks in the total PTSD symptom severity, in each symptom cluster and in Global Assessment of Functioning but did not yield significant improvement in symptoms of depression and had a high rate of side effects.

Adult↗

Molecular characterization and phylogenetic analyses of a new simian T cell lymphotropic virus type 1 in a wild-caught african baboon (Papio anubis) with an indeterminate STLV type 2-like serology.

STLV-1 viruses are closely related to HTLV-1 and infect many African monkey species. Seroreactivities of monkeys infected by STLV-1 are nearly identical to those of HTLV-1-infected individuals. In some cases, STLV-1 are, sequence-wise, indistinguishable from HTLV-1, and cannot be separated from them on the basis of phylogenetic analyses. HTLV-2-related simian viruses have been rarely reported. Such STLV-2 viruses, present in African bonobo (Pan paniscus), possess a genomic organization related to but different from all known HTLV-2 subtypes. We report here the molecular characterization and the subtyping of a new STLV-1 in a wild-caught baboon (Papio anubis) whose serum exhibited an indeterminate STLV-2-like serology (p24, GD21, MTA-1 with no p19). In the env and LTR regions, this virus is phylogenetically related to the large African STLV-1 group, but does not cluster with any STLV-1 baboon sequence. The complete p19 sequence reveals amino acid changes at critical positions. This is the first report of an African STLV-1 virus leading to an STLV-2-like serological profile in its host.

Amino Acid Sequence↗

Notch signalling and the synchronization of the somite segmentation clock.

In vertebrates with mutations in the Notch cell-cell communication pathway, segmentation fails: the boundaries demarcating somites, the segments of the embryonic body axis, are absent or irregular. This phenotype has prompted many investigations, but the role of Notch signalling in somitogenesis remains mysterious. Somite patterning is thought to be governed by a "clock-and-wavefront" mechanism: a biochemical oscillator (the segmentation clock) operates in the cells of the presomitic mesoderm, the immature tissue from which the somites are sequentially produced, and a wavefront of maturation sweeps back through this tissue, arresting oscillation and initiating somite differentiation. Cells arrested in different phases of their cycle express different genes, defining the spatially periodic pattern of somites and controlling the physical process of segmentation. Notch signalling, one might think, must be necessary for oscillation, or to organize subsequent events that create the somite boundaries. Here we analyse a set of zebrafish mutants and arrive at a different interpretation: the essential function of Notch signalling in somite segmentation is to keep the oscillations of neighbouring presomitic mesoderm cells synchronized.

Animals↗

A transcription map of the minimally deleted region from 13q14 in B-cell chronic lymphocytic leukemia as defined by large scale sequencing of the 650 kb critical region.

Extensive analysis of tumors has demonstrated homozygous and heterozygous deletions in chromosome region 13q14.3 in B-cell chronic lymphocytic leukemia (B-CLL), suggesting the site of a tumor suppressor gene. Since previous searches for this gene have not yielded any viable candidates, we now present the sequence of the BACs which span the minimally deleted approximately 650 kb region between markers D13S319 and D13S25. This sequence has allowed us to create the definitive transcription map for the region which reveals 93 ESTs and 12 Unigene clusters in this region. Using gene prediction programs, a further 19 potential genes are also identified. The genes show an asymmetrical distribution throughout the region with most of them clustering at the extreme ends. This sequencing effort provides for the definitive structure of the B-CLL deletion region and the identification of the vast majority of the potential candidate genes. Of all the genes identified, only three have homologies to known genes: two L1 repeat genes and rabbit epididymal protein 52. This 13q14.3 sequence provides the final substrate from which to characterize the B-CLL tumor suppressor gene.

Chromosomes, Artificial, Bacterial↗

Notch signaling in the development of the inner ear: lessons from Drosophila.

The sensory patches in the ear of a vertebrate can be compared with the mechanosensory bristles of a fly. This comparison has led to the discovery that lateral inhibition mediated by the Notch cell-cell signaling pathway, first characterized in Drosophila and crucial for bristle development, also has a key role in controlling the pattern of sensory hair cells and supporting cells in the ear. We review the arguments for considering the sensory patches of the vertebrate ear and bristles of the insect to be homologous structures, evolved from a common ancestral mechanosensory organ, and we examine more closely the role of Notch signaling in each system. Using viral vectors to misexpress components of the Notch pathway in the chick ear, we show that a simple lateral-inhibition model based on feedback regulation of the Notch ligand Delta is inadequate for the ear just as it is for the fly bristle. The Notch ligand Serrate1, expressed in supporting cells in the ear, is regulated by lateral induction, not lateral inhibition; commitment to become a hair cell is not simply controlled by levels of expression of the Notch ligands Delta1, Serrate1, and Serrate2 in the neighbors of the nascent hair cell; and at least one factor, Numb, capable of blocking reception of lateral inhibition is concentrated in hair cells. These findings reinforce the parallels between the vertebrate ear and the fly bristle and show how study of the insect system can help us understand the vertebrate.

Animals↗

Fear of falling.

Explore the source record for details and available documents.

Adolescent↗

Sensory organ generation in the chicken inner ear: contributions of bone morphogenetic protein 4, serrate1, and lunatic fringe.

The chicken inner ear is a remarkably complex structure consisting of eight morphologically distinct sensory organs. Unraveling how these sensory organs are specified during development is key to understanding how such a complex structure is generated. Previously, we have shown that each sensory organ in the chicken inner ear arises independently in the rudimentary otocyst based on Bone morphogenetic protein 4 (Bmp4) expression. Here, we compare the expression of Bmp4 with two other putative sensory organ markers, Lunatic Fringe (L-fng) and chicken Serrate1 (Ser1), both of which are components of the Notch signaling pathway. L-fng and Ser1 expression domains were asymmetrically distributed in the otic cup. At this early stage, expression of L-fng is similar to Delta1 (Dl1), in an anteroventral domain apparently corresponding to the neurogenic region, while Ser1 is expressed at both the anterior and posterior poles. By the otocyst stage, the expression of both L-fng and Ser1 largely coincided in the medial region. All presumptive sensory organs, as identified by Bmp4 expression, arose within the broad L-fng- and Ser1-positive domain, indicating the existence of a sensory-competent region in the rudimentary otocyst. In addition, there is a qualitative difference in the levels of expression between L-fng and Ser1 such that L-fng expression was stronger in the ventral anterior, whereas Ser1 was stronger in the dorsal posterior region of this broad domain. This early difference in expression may presage the differences among sensory organs as they arise from this sensory competent zone.

Age Factors↗