RESUMO
The aim of this study was to identify the causative factors of porcine ear necrosis syndrome (PENS) in 72 pigs, 5.5-10 weeks in age housed on nine farms. Biopsy samples of ear pinnae were collected from all piglets for bacteriology, histopathology and in situ hybridization for porcine circovirus type 2 (PCV2). At the same time, serum samples were taken for serological analysis and viral PCR, and feed was sampled for mycotoxin analysis. The initial lesion of PENS seemed to be a focal epidermal necrosis. Streptococci were isolated from 44 and staphylococci from 36 pinnae. PCV2 could not be detected by in situ hybridization or qPCR. Seven piglets were positive for porcine reproductive and respiratory syndrome virus, and one for Mycoplasma suis. One piglet had antibodies against Sarcoptes scabiei var. suis. No infectious agents were found in 15 samples. Positive virology and parasitology were often found alongside positive bacteriology. Deoxynivalenol, zearalenone and ergot alkaloids were detected in feed. The findings suggest that PENS is multifactorial in origin and that although infectious agents can be involved in the development of the syndrome they are not the exclusive triggering factor.
Assuntos
Otopatias/veterinária , Orelha/patologia , Necrose/veterinária , Doenças dos Suínos/etiologia , Doenças dos Suínos/patologia , Ração Animal/análise , Ração Animal/toxicidade , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Cromatografia Líquida de Alta Pressão/veterinária , Contagem de Colônia Microbiana/veterinária , Orelha/microbiologia , Orelha/parasitologia , Orelha/virologia , Otopatias/epidemiologia , Otopatias/etiologia , Otopatias/patologia , Micotoxinas/análise , Micotoxinas/toxicidade , Necrose/epidemiologia , Necrose/etiologia , Necrose/patologia , Suínos , Doenças dos Suínos/epidemiologiaRESUMO
The elimination of a hydrogen bond in imidazolium based ionic liquids which results in an increased melting point is investigated by means of static quantum chemical and molecular dynamics simulations.
Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Síndrome de Kallmann/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Translocação Genética , Adulto , Sequência de Bases , Mapeamento Cromossômico , Cromossomos Humanos Par 7 , Cromossomos Humanos Par 8 , Análise Mutacional de DNA , Humanos , Hibridização in Situ Fluorescente , Masculino , Proteínas dos Microfilamentos/genética , Dados de Sequência Molecular , Proteínas Mutantes Quiméricas/genética , TensinasRESUMO
PURPOSE: To assess the frequency of RPGR and RP2 mutations in a set of 85 patients with X-linked retinitis pigmentosa (XLRP) and to compare the visual function of patients with mutations in RPGR versus RP2. METHODS: Eighty-five unrelated patients with XLRP were ascertained, mainly from North America. The single-strand conformation polymorphism (SSCP) and a direct sequencing technique were used to screen their DNA for mutations in the coding region and splice sites of RPGR and RP2. The Snellen visual acuities, visual field areas, and 0.5-Hz and 30-Hz electroretinograms (ERGs) were measured in male patients. The visual function parameters were compared using multiple regression analysis. RESULTS: A wide spectrum of mutations was found in both genes, including missense, nonsense, splice-site, and frameshift mutations. Twenty putative pathogenic mutations in RPGR, 15 of which were novel, were found in 22 patients (26%), whereas 6 mutations in RP2, 4 of which were novel, were found in 6 patients (7%). A high fraction of the mutations in both genes affected amino acid residues within or adjacent to presumed functional domains. Comparison of visual function between comparably aged patients with mutations in RPGR versus RP2 showed that, on average, patients with RPGR mutations have lower ERG amplitudes and smaller visual field areas. CONCLUSIONS: Mutations in RPGR and RP2 genes together account for approximately 33% of cases of XLRP in North America. Patients with RPGR mutations have less overall retinal function on average than those with RP2 mutations, on the basis of measurements of visual field areas and full-field ERG amplitudes.
Assuntos
Proteínas de Transporte/genética , Proteínas do Olho , Ligação Genética , Mutação , Proteínas/genética , Retinose Pigmentar/genética , Acuidade Visual/fisiologia , Cromossomo X , Adolescente , Adulto , Sequência de Aminoácidos , Criança , Análise Mutacional de DNA , Eletrorretinografia , Feminino , Proteínas de Ligação ao GTP , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , Polimorfismo Genético , Polimorfismo Conformacional de Fita Simples , Retina/fisiopatologia , Retinose Pigmentar/fisiopatologia , Campos VisuaisRESUMO
Genetic screening has opened up new paths for progress in preventive and curative medicine, and will probably progressively increase its positive contribution in the future. Rules and regulations have been established attempting to protect the donors' rights and to avoid damage to the donor and to others. Present day regulations seem unable to prevent the occurrence of serious problems and possible dangers. These are: 1. Ownership of genetic information and right to determine to whom it is divulged. 2. Direct emotional damage to individuals (mainly young persons expecting late-onset catastrophes) by having the information. 3. Damage caused by unsought for findings. 4. Restriction of transfer of information to the stated aim. 5. Right to release information important for public safety. The aim of this article is to propose that the donor's ownership of the information be abolished and that a board should decide to whom the genetic information should be given. An alternative solution is to leave the decisions regarding to whom genetic information should be divulged in the hands of the donor and his physician, controlled by an institutional review board.
Assuntos
Confidencialidade/legislação & jurisprudência , Testes Genéticos/legislação & jurisprudência , Princípios Morais , Segurança Computacional/legislação & jurisprudência , Bases de Dados Factuais/legislação & jurisprudência , Ética Médica , HumanosRESUMO
Genetic loci for X-linked retinitis pigmentosa (XLRP) have been mapped between Xp11.22 and Xp22.13 (RP2, RP3, RP6, and RP15). The RP3 gene, which is responsible for the predominant form of XLRP in most Caucasian populations, has been localized to Xp21.1 by linkage analysis and the map positions of chromosomal deletions associated with the disease. Previous linkage studies have suggested that RP3 is flanked by the markers DXS1110 (distal) and OTC (proximal). Patient BB was thought to have RP because of a lesion at the RP3 locus, in addition to chronic granulomatous disease, Duchenne muscular dystrophy (DMD), mild mental retardation, and the McLeod phenotype. This patient carried a deletion extending approximately 3 Mb from DMD in Xp21.3 to Xp21.1, with the proximal breakpoint located approximately 40 kb centromeric to DXS1110. The RP3 gene, therefore, is believed to reside between DXS1110 and the proximal breakpoint of the BB deletion. In order to refine the location of RP3 and to ascertain patients with RP3, we have been analyzing several XLRP families for linkage to Xp markers. Linkage analysis in an American family of 27 individuals demonstrates segregation of XLRP with markers in Xp21.1, consistent with the RP3 subtype. One affected mate shows a recombination event proximal to DXS1110. Additional markers within the DXS1110-OTC interval show that the crossover is between two novel polymorphic markers, DXS8349 and M6, both of which are present in BB DNA and lie centromeric to the proximal breakpoint. This recombination places the XLRP mutation in this family outside the BB deletion and redefines the location of RP3.
Assuntos
Ligação Genética , Recombinação Genética , Retinose Pigmentar/genética , Cromossomo X/genética , Adulto , Sequência de Bases , Mapeamento Cromossômico , Primers do DNA/genética , Eletrorretinografia , Feminino , Marcadores Genéticos , Humanos , Escore Lod , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , Retinose Pigmentar/fisiopatologia , Deleção de SequênciaRESUMO
We report the mapping of the human and mouse genes encoding SEK1 (SAPK/ERK kinase-1), a newly identified protein kinase that is a potent physiological activator of the stress-activated protein kinases. The human SERK1 gene was assigned to human chromosome 17 using genomic DNAs from human-rodent somatic cell hybrid lines. A specific human PCR product was observed solely in the somatic cell line containing human chromosome 17. The mouse Serk1 gene was mapped to chromosome 11, closely linked to D11Mit4, using genomic DNAs from a (C57BL/6J x Mus spretus)F1 x M. spretus backcross.
Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 17 , MAP Quinase Quinase 4 , Quinases de Proteína Quinase Ativadas por Mitógeno , Proteínas Quinases/genética , Alelos , Animais , Sequência de Bases , Sequência Conservada , Cricetinae , Cruzamentos Genéticos , Ligação Genética , Humanos , Células Híbridas , Hibridização in Situ Fluorescente , Camundongos , Camundongos Endogâmicos C57BL , Muridae , Reação em Cadeia da Polimerase , Proteínas Quinases/biossínteseRESUMO
The Ikaros gene is an essential regulator in the development and homeostasis of the mouse lymphopoietic system. To study the role of the Ikaros gene in the human lymphopoietic system, we cloned and characterized human Ikaros cDNAs. In the human, as in the mouse, differential splicing of Ikaros primary transcripts generates a family of lymphoid-restricted zinc finger DNA binding proteins, highly conserved in sequence composition and relative expression to the mouse homologues. Expression of Ikaros isoforms is highly restricted to the lymphopoietic system and is particularly enriched in maturing thymocytes. The Ikaros gene maps at a syntenic locus located on the short arm of human chromosome 7 and on mouse chromosome 11 next to the epidermal growth factor receptor (Egfr). The high degree of conservation of the Ikaros gene at the genetic and expression levels strongly suggests that it plays a fundamental role in the ontogeny of the lymphopoietic system across species.
Assuntos
Proteínas de Ligação a DNA , Hematopoese/genética , Camundongos/genética , Família Multigênica , Fatores de Transcrição/genética , Dedos de Zinco/genética , Células 3T3 , Sequência de Aminoácidos , Animais , Sequência de Bases , Mapeamento Cromossômico , Cromossomos Humanos Par 7 , DNA Complementar/genética , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Fator de Transcrição Ikaros , Leucemia-Linfoma de Células T do Adulto/patologia , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Splicing de RNA , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Células Tumorais CultivadasRESUMO
The WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) deletion region on chromosome 11p13 has been extensively characterized by deletion analysis and long-range restriction mapping. A dense probe set is available for this genomic region, which harbors a number of disease gene loci, some of which still are not cloned. The identification of candidates for these genes would be greatly facilitated by a complete gene map for this chromosomal segment. As an initial step toward this goal, we have isolated the entire region in 58 overlapping YAC clones. The contig spanning 8 Mb from RAG1 to KCNA4 has been assembled by STS and probe content mapping for 76 loci with an average spacing of about 100 kb. A subset of clones has been analyzed by PFG analysis to position these within the known physical map. Common microsatellite markers permit an alignment of the YAC contig with the genetic and radiation hybrid maps of chromosome 11. Ten known genes, some with much more refined map positions, are placed in the contig. The severalfold coverage of 11p13-p14.1 provides a reliable resource for the future development of a complete gene map of this region.
Assuntos
Mapeamento Cromossômico , Cromossomos Artificiais de Levedura/química , Cromossomos Artificiais de Levedura/genética , Cromossomos Humanos Par 11 , Proteínas de Homeodomínio , Síndrome WAGR/genética , Sequência de Bases , Cloranfenicol O-Acetiltransferase/genética , Clonagem Molecular/métodos , Sondas de DNA , Bases de Dados Factuais , Biblioteca Gênica , Marcadores Genéticos , Humanos , Hibridização In Situ , Dados de Sequência Molecular , Proteínas/genéticaAssuntos
Evolução Biológica , Cromossomos Humanos Par 5 , Proteínas de Ligação a DNA/genética , Fatores de Regulação Miogênica , Fatores de Transcrição/genética , Animais , Sequência de Bases , Encéfalo/metabolismo , Mapeamento Cromossômico , Sequência Conservada , Primers do DNA , Biblioteca Gênica , Humanos , Células Híbridas , Cariotipagem , Proteínas de Domínio MADS , Fatores de Transcrição MEF2 , Mamíferos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Mapeamento por Restrição , RoedoresRESUMO
A new gene (239FB) with predominant and differential expression in fetal brain has recently been isolated from a chromosome 11p13-p14 boundary area near FSHB. The corresponding mRNA has an open reading frame of 294 amino acids, a 3' untranslated region of 1247 nucleotides, and a highly GC-rich 5' untranslated region. The coding and 3' UT sequence is specified by 6 exons within nearly 87 kb of isolated genomic locus. The 5' end region of the transcript maps adjacent to the only genomically defined CpG island in a chromosomal subregion that may be associated with part of the mental retardation of some WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome patients. In addition to nucleotide and amino acid similarity to an EST from a normalized infant brain cDNA library, the predicted protein has extensive similarity to two Caenorhabditis elegans polypeptides of, as yet, unknown function. The 239FB locus is, therefore, likely part of a family of genes with two members expressed in human brain. The extensive conservation of the predicted protein suggests a fundamental function of the gene product and will enable evaluation of the role of the 239FB gene in neurogenesis in model organisms.
Assuntos
Evolução Biológica , Encéfalo/metabolismo , Cromossomos Humanos Par 11 , Síndrome WAGR/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Encéfalo/embriologia , Caenorhabditis elegans/genética , Galinhas/genética , Mapeamento Cromossômico , Clonagem Molecular , Sequência Conservada , DNA Complementar , Éxons , Feto , Biblioteca Gênica , Humanos , Íntrons , Dados de Sequência Molecular , Fases de Leitura Aberta , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Mapeamento por Restrição , Homologia de Sequência de AminoácidosRESUMO
Developmental delay or mental retardation is a frequent component of multi-system anomaly syndromes associated with chromosomal deletions. Isolation of genes involved in the mental dysfunction in these disorders should define loci important in brain formation or function. We have identified a highly conserved locus in the distal part of 11p13 that is prominently expressed in fetal brain. Minimal expression is observed in a number of other fetal tissues. The gene maps distal to PAX-6 but proximal to the loci for brain-derived neurotrophic factor (BDNF) and the beta subunit of follicle stimulating hormone (FSHB), within a region previously implicated in the mental retardation component of some WAGR syndrome patients. Within fetal brain, the corresponding transcript is prominent in frontal, motor and primary visual cortex as well as in the caudate-putamen. The characteristics of this gene, including the striking evolutionary conservation at the locus, suggest that the encoded protein may function in brain development.
Assuntos
Encéfalo/embriologia , Deleção de Genes , Transcrição Gênica/genética , Síndrome WAGR/genética , Northern Blotting , Mapeamento Cromossômico , Expressão Gênica , Humanos , RNA/análiseRESUMO
We wished to characterize MDL 28,133A (1-(4-fluorophenyl)-2-[4-[(4-methanesulfonamidophenyl)carbonyl]-1- piperidinyl-ethanone HCl), a potent 5-HT2 receptor antagonist, on platelet aggregation and platelet thrombosis and determined its effect on thrombolysis with streptokinase (SK) in dogs with coronary thrombosis. MDL 28,133A and ritanserin, 0.3-1 microM, competitively inhibited 5-HT-induced platelet aggregation in dog platelet-rich plasma (PRP) in vitro. The pA2 values and slopes were 6.29 +/- 0.09, -0.96 +/- 0.14, and 6.58 +/- 0.09, =1.64 +/- 0.34 for MDL 28,133A and ritanserin, respectively, suggesting that both agents are similar in potency to 5-HT2 receptor antagonists. MDL 28,133A (0.01 mg/kg, p.o.) produced inhibition of arachidonic acid-induced platelet aggregation in whole blood from conscious dogs ex vivo for > or = 2 h, indicating oral bioavailability. The magnitude and duration of the effect of MDL 28,133A on platelet aggregation in whole blood was similar to that of ketanserin (2.5 mg/kg, p.o.). MDL 28,133A (0.001-0.03 mg/kg, i.v.) completely abolished cyclic flow reductions (CFRs) in stenosed and partially deendothelialized left anterior descending coronary arteries of anesthetized dogs for at least 120 min without affecting systemic blood pressure (BP) and heart rate, thus indicating that MDL 28,133A is a potent antithrombotic agent. Ketanserin (0.5 mg/kg, i.v.) also abolished CFRs, but produced a significant decrease in systemic BP as well. MDL 28,133A (0.001 mg/kg, i.v.) shortened time to reperfusion (15 +/- 1 vs. 36 +/- 8 min), prolonged time to reocclusion (112 +/- 6 vs. 85 +/- 6 min), and increased total volume reflow (20 +/- 2 vs. 10 +/- 2%) in dogs with coronary artery thrombosis undergoing thrombolysis with SK (1,000 U/min, i.a.). Reocclusion rate was not affected by MDL 28,133A (4 of 5 vs. 4 of 6). Treatment with heparin (150 U/kg, i.v. every hour for 2 h) alone or in combination with MDL 28,133A did not improve time to reperfusion but enhanced total volume reflow and prevented reocclusion. MDL 28,133A is a potent 5-HT2 receptor antagonist that inhibits platelet thrombosis and facilitates thrombolysis in vivo. The impeding effect of MDL 28,133A in coronary thrombosis and the lack of hemodynamic effects suggests that MDL 28,133A may be of benefit in treatment of hyperthrombotic conditions without having hemodynamic side effects.
Assuntos
Trombose Coronária/tratamento farmacológico , Piperidinas/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Antagonistas da Serotonina/farmacologia , Administração Oral , Animais , Disponibilidade Biológica , Plaquetas/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Cães , Quimioterapia Combinada , Estimulação Elétrica , Feminino , Frequência Cardíaca/efeitos dos fármacos , Heparina/administração & dosagem , Heparina/farmacologia , Heparina/uso terapêutico , Técnicas In Vitro , Masculino , Piperidinas/administração & dosagem , Piperidinas/uso terapêutico , Ritanserina/administração & dosagem , Ritanserina/farmacologia , Ritanserina/uso terapêutico , Serotonina/metabolismo , Serotonina/toxicidade , Antagonistas da Serotonina/administração & dosagem , Antagonistas da Serotonina/uso terapêutico , Estreptoquinase/administração & dosagem , Estreptoquinase/farmacologia , Estreptoquinase/uso terapêuticoAssuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 10 , Lectinas Tipo C , Lectinas de Ligação a Manose , Receptores de Superfície Celular/genética , Animais , Sequência de Bases , Cromossomos Humanos Par 10/ultraestrutura , Primers do DNA/genética , Humanos , Células Híbridas , Hibridização in Situ Fluorescente , Macrófagos/metabolismo , Receptor de Manose , Camundongos , Dados de Sequência Molecular , Reação em Cadeia da PolimeraseAssuntos
Camundongos Endogâmicos/genética , Polimorfismo Genético , Animais , Sequência de Bases , Southern Blotting , DNA/análise , Primers do DNA , Marcadores Genéticos , Camundongos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Mapeamento por Restrição , Especificidade da EspécieRESUMO
Actin-binding protein-280 (ABP-280) is a dimeric actin filament crosslinking protein that promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. We have mapped the ABP-280 filamin gene (FLN) to Xq28 by Southern blot analysis of somatic cell hybrid lines, by fluorescence in situ hybridization, and through identification of portions of the FLN gene within cosmids and YACs mapped to Xq28. The FLN gene is found within a 200-kb region centromeric to the G6PD locus and telomeric to DSX52 and the color vision locus.