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Full-Text Articles in Medicine and Health Sciences
Characterization Of A Far-Red Analog Of Ghrelin For Imaging Ghs-R In P19-Derived Cardiomyocytes., Gregory A F Douglas, Rebecca Mcgirr, Carlie L Charlton, Dov B Kagan, Lisa M Hoffman, Leonard G Luyt, Savita Dhanvantari
Characterization Of A Far-Red Analog Of Ghrelin For Imaging Ghs-R In P19-Derived Cardiomyocytes., Gregory A F Douglas, Rebecca Mcgirr, Carlie L Charlton, Dov B Kagan, Lisa M Hoffman, Leonard G Luyt, Savita Dhanvantari
Lisa Hoffman
Ghrelin and its receptor, the growth hormone secretagogue receptor (GHS-R), are expressed in the heart, and may function to promote cardiomyocyte survival, differentiation and contractility. Previously, we had generated a truncated analog of ghrelin conjugated to fluorescein isothiocyanate for the purposes of determining GHS-R expression in situ. We now report the generation and characterization of a far-red ghrelin analog, [Dpr(3)(octanoyl), Lys(19)(Cy5)]ghrelin (1-19), and show that it can be used to image changes in GHS-R in developing cardiomyocytes. We also generated the des-acyl analog, des-acyl [Lys(19)(Cy5)]ghrelin (1-19) and characterized its binding to mouse heart sections. Receptor binding affinity of Cy5-ghrelin as …
Bacterial Rna:Dna Hybrids Are Activators Of The Nlrp3 Inflammasome, Sivapriya Kailasan Vanaja, Vijay A. K. Rathinam, Maninjay K. Atianand, Parisa Kalantari, Brian M. Skehan, Katherine A. Fitzgerald, John M. Leong
Bacterial Rna:Dna Hybrids Are Activators Of The Nlrp3 Inflammasome, Sivapriya Kailasan Vanaja, Vijay A. K. Rathinam, Maninjay K. Atianand, Parisa Kalantari, Brian M. Skehan, Katherine A. Fitzgerald, John M. Leong
Katherine A. Fitzgerald
Enterohemorrhagic Escherichia coli (EHEC) is an extracellular pathogen that causes hemorrhagic colitis and hemolytic uremic syndrome. The proinflammatory cytokine, interleukin-1beta, has been linked to hemolytic uremic syndrome. Here we identify the nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome as an essential mediator of EHEC-induced IL-1beta. Whereas EHEC-specific virulence factors were dispensable for NLRP3 activation, bacterial nucleic acids such as RNA:DNA hybrids and RNA gained cytosolic access and mediated inflammasome-dependent responses. Consistent with a direct role for RNA:DNA hybrids in inflammasome activation, delivery of synthetic EHEC RNA:DNA hybrids into the cytosol triggered NLRP3-dependent responses, …
Analysis Of Murine Cd8(+) T-Cell Clones Specific For The Dengue Virus Ns3 Protein: Flavivirus Cross-Reactivity And Influence Of Infecting Serotype, Anne C. Spaulding, Ichiro Kurane, Francis A. Ennis, Alan L. Rothman
Analysis Of Murine Cd8(+) T-Cell Clones Specific For The Dengue Virus Ns3 Protein: Flavivirus Cross-Reactivity And Influence Of Infecting Serotype, Anne C. Spaulding, Ichiro Kurane, Francis A. Ennis, Alan L. Rothman
Alan Rothman
Serotype-cross-reactive dengue virus-specific cytotoxic T lymphocytes (CTL) induced during a primary dengue virus infection are thought to play a role in the immunopathogenesis of dengue hemorrhagic fever (DHF) during a secondary dengue virus infection. Although there is no animal model of DHF, we previously reported that murine dengue virus-specific CTL responses are qualitatively similar to human dengue virus-specific CTL responses. We used BALB/c mice to study the specificity of the CTL response to an immunodominant epitope on the dengue virus NS3 protein. We mapped the minimal H-2Kd-restricted CTL epitope to residues 298 to 306 of the dengue type 2 virus …
Definition Of An Hla-Dpw2-Restricted Epitope On Ns3, Recognized By A Dengue Virus Serotype-Cross-Reactive Human Cd4+ Cd8- Cytotoxic T-Cell Clone, Ichiro Kurane, Li Chen Dai, Peter G. Livingston, Elaine Reed, Francis A. Ennis
Definition Of An Hla-Dpw2-Restricted Epitope On Ns3, Recognized By A Dengue Virus Serotype-Cross-Reactive Human Cd4+ Cd8- Cytotoxic T-Cell Clone, Ichiro Kurane, Li Chen Dai, Peter G. Livingston, Elaine Reed, Francis A. Ennis
Li Dai
We previously reported that the clone JK34 was cross-reactive for dengue virus types 1, 2, 3, and 4 and recognized NS3 (I. Kurane, M. A. Brinton, A. L. Samson, and F. A. Ennis, J. Virol. 65:1823-1828, 1991). In the present experiments, we defined the epitope at the amino acid level, with 93 15-mer overlapping peptides which cover the entire NS3. A peptide 4 which contains amino acids 251 to 265 of NS3 sensitized the autologous B lymphoblastoid cell line (LCL) to the lysis by JK34. The smallest peptide recognized by JK34 was a 10-mer peptide which contains amino acids 255 …
Mutation Of Human Immunodeficiency Virus Type 1 At Amino Acid 585 On Gp41 Results In Loss Of Killing By Cd8+ A24-Restricted Cytotoxic T Lymphocytes, Li Chen Dai, Kim West, Rebecca A. Littaua, Kazuo Takahashi, Francis A. Ennis
Mutation Of Human Immunodeficiency Virus Type 1 At Amino Acid 585 On Gp41 Results In Loss Of Killing By Cd8+ A24-Restricted Cytotoxic T Lymphocytes, Li Chen Dai, Kim West, Rebecca A. Littaua, Kazuo Takahashi, Francis A. Ennis
Li Dai
A human leukocyte antigen A24-restricted CD8+ cytotoxic T-cell clone specific for gp41 of human immunodeficiency virus type 1 was isolated from an infected individual. The epitope was localized to amino acids 584 to 591 (YLKDQQLL, NL43 env sequence) of gp41 by using a panel of recombinant vaccinia viruses that contain truncated env genes and synthetic peptides. The clone killed autologous B-lymphoblastoid cell lines pulsed with a synthetic peptide reflecting the sequence of the IIIB and MN strains. This clone, however, failed to kill target cells pulsed with the peptides that have a mutation from Lys to Arg or Gln at …
A Novel Activating Mutation In Transmembrane Helix 6 Of The Thyrotropin Receptor As Cause Of Hereditary Nonautoimmune Hyperthyroidism, Benjamin U. Nwosu, Loukas Gourgiotis, Marvin C. Gershengorn, Susanne Neumann
A Novel Activating Mutation In Transmembrane Helix 6 Of The Thyrotropin Receptor As Cause Of Hereditary Nonautoimmune Hyperthyroidism, Benjamin U. Nwosu, Loukas Gourgiotis, Marvin C. Gershengorn, Susanne Neumann
Benjamin U. Nwosu
Constitutively-activating germline mutations of the thyrotropin receptor (TSHR) gene are very rare and are considered the cause of hereditary nonautoimmune hyperthyroidism. We describe four affected individuals from a Caucasian family: a mother and her three children, and an unaffected father. The mother and her first two children presented in a similar manner: lifelong histories of heat intolerance, hyperactivity, fast heart rate, reduced energy, increased appetite, and scrawny build. They all developed goiter in childhood and showed a suppressed TSH and elevated thyroxine (T(4)). The last child, a 12-year-old female, presented with no clinical symptoms or palpable neck mass, but with …
Complete Sequencing Shows A Role For Msx1 In Non-Syndromic Cleft Lip And Palate, P. A. Jezewski, A. R. Vieira, C. Nishimura, B. Ludwig, M. Johnson, S. E. O'Brien, Sandra Daack-Hirsch, R. E. Schultz, A. Weber, B. Nepomucena, P. A. Romitti, K. Christensen, I. M. Orioli, E. E. Castilla, J. Machida, N. Natsume, J. C. Murray
Complete Sequencing Shows A Role For Msx1 In Non-Syndromic Cleft Lip And Palate, P. A. Jezewski, A. R. Vieira, C. Nishimura, B. Ludwig, M. Johnson, S. E. O'Brien, Sandra Daack-Hirsch, R. E. Schultz, A. Weber, B. Nepomucena, P. A. Romitti, K. Christensen, I. M. Orioli, E. E. Castilla, J. Machida, N. Natsume, J. C. Murray
Sandra Daack-Hirsch
MSX1 has been proposed as a gene in which mutations may contribute to non-syndromic forms of cleft lip and/or cleft palate. Support for this comes from human linkage and linkage disequilibrium studies, chromosomal deletions resulting in haploinsufficiency, a large family with a stop codon mutation that includes clefting as a phenotype, and the Msx1 phenotype in a knockout mouse. This report describes a population based scan for mutations encompassing the sense and antisense transcribed sequence of MSX1 (two exons, one intron). We compare the completed genomic sequence of MSX1 to the mouse Msx1 sequence to identify non-coding homology regions, and …
Detection Of Naegleria Species In Environmental Samples From Peninsular Malaysia, Init Ithoi
Detection Of Naegleria Species In Environmental Samples From Peninsular Malaysia, Init Ithoi
Init Ithoi
Background: In Malaysia, researchers and medical practitioners are unfamiliar with Naegleria infections. Thus little is known about the existence of pathogenic Naegleria fowleri, and the resultant primary amoebic meningoencephalitis (PAM) is seldom included in the differential diagnosis of central nervous system infections. This study was conducted to detect the presence of Naegleria species in various environmental samples. Methods/Findings: A total of 41 Naegleria-like isolates were isolated from water and dust samples. All these isolates were subjected to PCR using two primer sets designed from the ITS1-ITS2 regions. The N. fowleri species-specific primer set failed to produce the expected amplicon. The …
Lps-Tlr4 Signaling To Irf-3/7 And Nf-Kappab Involves The Toll Adapters Tram And Trif, Katherine A. Fitzgerald, Daniel C. Rowe, Betsy J. Barnes, Daniel R. Caffrey, Alberto Visintin, Eicke Latz, Brian G. Monks, Paula M. Pitha, Douglas T. Golenbock
Lps-Tlr4 Signaling To Irf-3/7 And Nf-Kappab Involves The Toll Adapters Tram And Trif, Katherine A. Fitzgerald, Daniel C. Rowe, Betsy J. Barnes, Daniel R. Caffrey, Alberto Visintin, Eicke Latz, Brian G. Monks, Paula M. Pitha, Douglas T. Golenbock
Katherine A. Fitzgerald
Toll-IL-1-resistance (TIR) domain-containing adaptor-inducing IFN-beta (TRIF)-related adaptor molecule (TRAM) is the fourth TIR domain-containing adaptor protein to be described that participates in Toll receptor signaling. Like TRIF, TRAM activates interferon regulatory factor (IRF)-3, IRF-7, and NF-kappaB-dependent signaling pathways. Toll-like receptor (TLR)3 and 4 activate these pathways to induce IFN-alpha/beta, regulated on activation, normal T cell expressed and secreted (RANTES), and gamma interferon-inducible protein 10 (IP-10) expression independently of the adaptor protein myeloid differentiation factor 88 (MyD88). Dominant negative and siRNA studies performed here demonstrate that TRIF functions downstream of both the TLR3 (dsRNA) and TLR4 (LPS) signaling pathways, whereas the …
Isolation And Characterization Of Acanthamoeba Spp. From Air-Conditioners In Kuala Lumpur, Malaysia, Init Ithoi
Isolation And Characterization Of Acanthamoeba Spp. From Air-Conditioners In Kuala Lumpur, Malaysia, Init Ithoi
Init Ithoi
During a study on the quality of the indoor environment, Acanthamoeba spp. were detected in 20 out of 87 dust samples collected from air-conditioners installed in a four-story campus building located in Kuala Lumpur, Malaysia. Twenty-one cloned Acanthamoeba isolates designated as IMU1 to IMU21 were established from the positive primary cultures. Five species were identified from the 16 isolates according to the morphological criteria of Pussard and Pons; i.e. A. castellanii, A. culbertsoni, A. griffini, A. hatchetti and A. polyphaga. Species identities for the remaining five isolates (IMU4, IMU5, IMU15, IMU20 and IMU21), however, could not be determined morphologically. At …
Regulation Of Alpha 6 Beta 1 Integrin Laminin Receptor Function By The Cytoplasmic Domain Of The Alpha 6 Subunit, Leslie M. Shaw, Arthur M. Mercurio
Regulation Of Alpha 6 Beta 1 Integrin Laminin Receptor Function By The Cytoplasmic Domain Of The Alpha 6 Subunit, Leslie M. Shaw, Arthur M. Mercurio
Arthur M. Mercurio
The alpha 6 beta 1 integrin is expressed on the macrophage surface in an inactive state and requires cellular activation with PMA or cytokines to function as a laminin receptor (Shaw, L. M., J. M. Messier, and A. M. Mercurio. 1990. J. Cell Biol. 110:2167-2174). In the present study, the role of the alpha 6 subunit cytoplasmic domain in alpha 6 beta 1 integrin activation was examined. The use of P388D1 cells, an alpha 6-integrin deficient macrophage cell line, facilitated this analysis because expression of either the alpha 6A or alpha 6B subunit cDNAs restores their activation responsive laminin adhesion …
Dirofilaria Causing Eye Infection In A Patient From Malaysia, Init Ithoi
Dirofilaria Causing Eye Infection In A Patient From Malaysia, Init Ithoi
Init Ithoi
During a study on the quality of the indoor environment, Acanthamoeba spp. were detected in 20 out of 87 dust samples collected from air-conditioners installed in a four-story campus building located in Kuala Lumpur, Malaysia. Twenty-one cloned Acanthamoeba isolates designated as IMU1 to IMU21 were established from the positive primary cultures. Five species were identified from the 16 isolates according to the morphological criteria of Pussard and Pons; i.e. A. castellanii, A. culbertsoni, A. griffini, A. hatchetti and A. polyphaga. Species identities for the remaining five isolates (IMU4, IMU5, IMU15, IMU20 and IMU21), however, could not be determined morphologically. At …
Supervillin (P205): A Novel Membrane-Associated, F-Actin-Binding Protein In The Villin/Gelsolin Superfamily, Kersi N. Pestonjamasp, Robert K. Pope, J. D. Wulfkuhle, Elizabeth J. Luna
Supervillin (P205): A Novel Membrane-Associated, F-Actin-Binding Protein In The Villin/Gelsolin Superfamily, Kersi N. Pestonjamasp, Robert K. Pope, J. D. Wulfkuhle, Elizabeth J. Luna
Elizabeth J. Luna
Actin-binding membrane proteins are involved in both adhesive interactions and motile processes. We report here the purification and initial characterization of p205, a 205-kD protein from bovine neutrophil plasma membranes that binds to the sides of actin filaments in blot overlays. p205 is a tightly bound peripheral membrane protein that cosediments with endogenous actin in sucrose gradients and immunoprecipitates. Amino acid sequences were obtained from SDS-PAGE-purified p205 and used to generate antipeptide antibodies, immunolocalization data, and cDNA sequence information. The intracellular localization of p205 in MDBK cells is a function of cell density and adherence state. In subconfluent cells, p205 …
Smooth Muscle Archvillin: A Novel Regulator Of Signaling And Contractility In Vascular Smooth Muscle, Samudra S. Gangopadhyay, Norio Takizawa, Cynthia Gallant, Amy L. Barber, Hyun-Dong Je, Tara C. Smith, Elizabeth J. Luna, Kathleen G. Morgan
Smooth Muscle Archvillin: A Novel Regulator Of Signaling And Contractility In Vascular Smooth Muscle, Samudra S. Gangopadhyay, Norio Takizawa, Cynthia Gallant, Amy L. Barber, Hyun-Dong Je, Tara C. Smith, Elizabeth J. Luna, Kathleen G. Morgan
Elizabeth J. Luna
The mechanisms by which protein kinase C (PKC) and extracellular-signal-regulated kinases (ERK1/2) govern smooth-muscle contractility remain unclear. Calponin (CaP), an actin-binding protein and PKC substrate, mediates signaling through ERK1/2. We report here that CaP sequences containing the CaP homology (CH) domain bind to the C-terminal 251 amino acids of smooth-muscle archvillin (SmAV), a new splice variant of supervillin, which is a known actin- and myosin-II-binding protein. The CaP-SmAV interaction is demonstrated by reciprocal yeast two-hybrid and blot-overlay assays and by colocalization in COS-7 cells. In differentiated smooth muscle, endogenous SmAV and CaP co-fractionate and co-translocate to the cell cortex after …
Archvillin, A Muscle-Specific Isoform Of Supervillin, Is An Early Expressed Component Of The Costameric Membrane Skeleton, Sang W. Oh, Robert K. Pope, Kelly P. Smith, Jessica Lynn Crowley, Thomas Nebl, Jeanne B. Lawrence, Elizabeth J. Luna
Archvillin, A Muscle-Specific Isoform Of Supervillin, Is An Early Expressed Component Of The Costameric Membrane Skeleton, Sang W. Oh, Robert K. Pope, Kelly P. Smith, Jessica Lynn Crowley, Thomas Nebl, Jeanne B. Lawrence, Elizabeth J. Luna
Elizabeth J. Luna
The membrane skeleton protein supervillin binds tightly to both F-actin and membranes and can potentiate androgen receptor activity in non-muscle cells. We report that muscle, which constitutes the principal tissue source for supervillin sequences, contains a approximately 250 kDa isoform of supervillin that localizes within nuclei and with dystrophin at costameres, regions of F-actin membrane attachment in skeletal muscle. The gene encoding this protein, 'archvillin' (Latin, archi; Greek, archos; 'principal' or 'chief'), contains an evolutionarily conserved, muscle-specific 5' leader sequence. Archvillin cDNAs also contain four exons that encode approximately 47 kDa of additional muscle-specific protein sequence in the form of …