RESUMO
OBJECTIVES: Dysphagia is common in older adults. However, there are no current estimates of dysphagia in community-dwelling older adults those receiving meal support. It is unknown whether dysphagia is associated with other measures of physical function (activities of daily living [ADL] ability or nutrition status). The study purposes were to determine the prevalence of self-reported dysphagia and to identify factors associated with self-reported dysphagia in community-dwelling older adults receiving meal support. DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: 476 community-dwelling older adults (78.5±0.51 years) across five Elder Nutrition Program meal services in Wisconsin participated in the study. MEASUREMENTS: Data were collected through administration of validated ADL and nutrition questionnaires (nutritional status, functional status with ADLs, chewing ability, dental conditions, and prior diagnoses of dysphagia, pneumonia, and dementia). For self-reported dysphagia, the validated 10-item eating assessment tool (EAT-10) was used. RESULTS: The prevalence of self-reported dysphagia (EAT-10 score of ≥ 3) was 20.4%. Multivariate logistic regression results indicated that poor nutritional status (OR=3.1, p=0.04), difficulty chewing (OR=2.2, p=0.03), prior dysphagia diagnosis (OR=34.8, p<0.001), prior pneumonia diagnosis (OR=2.1, p=0.04), and meal service site (OR=2.68, p=0.02) were associated with self-reported dysphagia. CONCLUSION: Approximately one in five community-dwelling older adults receiving meal support had self-reported dysphagia. Increased risk for poor nutrition, reduced chewing ability, prior dysphagia and pneumonia diagnosis, and meal service site were identified as factors associated with dysphagia on the EAT-10. Results highlight the need for further studies across more sites to identify dysphagia risk indicators in community-dwelling older adults receiving meal support state-wide.
Assuntos
Transtornos de Deglutição , Desnutrição , Atividades Cotidianas , Idoso , Estudos Transversais , Transtornos de Deglutição/complicações , Avaliação Geriátrica , Humanos , Vida Independente , Desnutrição/diagnóstico , Estado Nutricional , AutorrelatoRESUMO
We consider the problem of model-based clustering in the presence of many correlated, mixed continuous, and discrete variables, some of which may have missing values. Discrete variables are treated with a latent continuous variable approach, and the Dirichlet process is used to construct a mixture model with an unknown number of components. Variable selection is also performed to identify the variables that are most influential for determining cluster membership. The work is motivated by the need to cluster patients thought to potentially have autism spectrum disorder on the basis of many cognitive and/or behavioral test scores. There are a modest number of patients (486) in the data set along with many (55) test score variables (many of which are discrete valued and/or missing). The goal of the work is to (1) cluster these patients into similar groups to help identify those with similar clinical presentation and (2) identify a sparse subset of tests that inform the clusters in order to eliminate unnecessary testing. The proposed approach compares very favorably with other methods via simulation of problems of this type. The results of the autism spectrum disorder analysis suggested 3 clusters to be most likely, while only 4 test scores had high (>0.5) posterior probability of being informative. This will result in much more efficient and informative testing. The need to cluster observations on the basis of many correlated, continuous/discrete variables with missing values is a common problem in the health sciences as well as in many other disciplines.
RESUMO
In this study, antibodies toward the transcription factors Prox1, Lim1, Ap2alpha, Pax6, Isl1, Isl2, Lim3 and Chx10 were used to identify and distinguish between developing cell types in the pre-laminated chick retina. The spatio-temporal expression patterns were analysed from embryonic day 3 (E3) to E9, thus covering a time-span from the onset of retinal cell-fate determination to when retinal laminas can be distinguished. Most transcription factors were found at early stages of development, enabling us to trace various precursor cell populations throughout the lamination process. With time, each transcription factor expression became restricted to distinct laminas or sub-laminas of the maturing retina. These early emerging patterns were compared and found to be consistent with those of the hatched chick retina, where the outer nuclear layer label for Lim3, Isl1 and Isl2. In the inner nuclear layer, horizontal cells labeled for Prox1, Lim1, Isl1, Ap2alpha and Pax6, bipolar cell labeled for Lim3, Isl1 and Chx10 and amacrine cells labeled for Ap2alpha, Isl1 and Pax6. The ganglion cell layer labeled for Isl1, Pax6 and Isl2. The immunolabeling patterns of Lim3 and Isl2 have not previously been described in detail.
Assuntos
Proteínas do Olho/imunologia , Imuno-Histoquímica , Retina/citologia , Fatores de Transcrição/imunologia , Animais , Anticorpos/metabolismo , Proteínas Aviárias/imunologia , Embrião de Galinha , Proteínas de Drosophila/imunologia , Proteínas do Olho/análise , Proteínas do Olho/classificação , Proteínas de Homeodomínio/imunologia , Proteínas com Homeodomínio LIM , Proteínas do Tecido Nervoso/imunologia , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados/imunologia , Proteínas Repressoras/imunologia , Retina/embriologia , Retina/metabolismo , Fatores de Tempo , Fator de Transcrição AP-2/imunologia , Fatores de Transcrição/análise , Proteínas Supressoras de TumorRESUMO
Deletions of the proximal portion of the long arm of chromosome 6 are rare, and the patients reported in the literature have been described as having significant mental retardation, often in the severe to profound range. We report on a young girl with a proximal 6q interstitial deletion [46, XX, del (6) (q1 3q15)] who exhibits the typical morphological and neurological manifestations except that the degree of language and non-language cognitive delay is mild. Cognitive development has been assessed using the Capute Scales. Gross motor development has been assessed clinically using standard milestones. At 34 months of age, she was found to have severe gross motor delay, with mildly delayed non-language cognitive abilities and expressive language abilities. Her receptive language skills tested in the average range. In recent years. several forms of autosomal dominant drusen and macular degeneration have been mapped to 6q14, and substantial variability in clinical expression has been described. Serial ophthalmologic examinations have not detected any drusen or atrophic macular changes in our patient. To our knowledge, this is the first description of a child with proximal 6q interstitial deletion in the documented absence of severe cognitive deficiency. This information may be important to clinicians who counsel families of infants determined to have proximal 6q interstitial deletions. Because the deleted region contains the area to which autosomal dominant drusen and macular degeneration has been mapped, we believe that this child is at risk for visual loss, and she will continue to be monitored closely.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 6/genética , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Anormalidades Múltiplas , Pré-Escolar , Feminino , Humanos , Degeneração Macular/genética , Índice de Gravidade de DoençaRESUMO
The glial-cell-line-derived neurotrophic factor (GDNF) family receptors alpha (GFRalpha) are cell surface bound glycoproteins that mediate interactions of the GDNF ligand family with the RET receptor. These interactions are crucial to the development of the kidney and some peripheral nerve lineages. In humans, mutations of RET or RET ligands are associated with the congenital abnormality Hirschsprung disease (HSCR) in which nerves and ganglia of the hind gut are absent. As the GFRalpha family are required for normal activation of the RET receptor, they are also candidates for a role in HSCR. The GFRA2 gene, which is required for the development of the myenteric nerve plexus, is an excellent candidate gene for HSCR. In this study, we cloned the human GFRA2 locus, characterized the gene structure, and compared it with other GFRA family members. We further investigated the GFRA2 gene for mutations in a panel of HSCR patients. GFRA2 has nine coding exons that are similar in size and organization to those of other GFRA family genes. We identified six sequence variants of GFRA2, four of which did not affect the amino acid sequence of the GFRalpha-2 protein. Two further changes that resulted in amino acid substitutions were found in exon 9 and were predicted to lie in the amino acid sequence encoding the glycosylphosphatidylinositol-linkage signal of GFRalpha-2. There was no difference in frequency of any of the sequence variants between control and HSCR populations. Our data indicate that members of the GFRA gene family are closely related in intron/exon structure and in sequence. We have not detected any correlation between sequence variants of GFRA2 and the HSCR phenotype.
Assuntos
Proteínas de Drosophila , Doença de Hirschsprung/genética , Mutação/genética , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Sequência de Bases , Clonagem Molecular , Análise Mutacional de DNA , Éxons/genética , Frequência do Gene/genética , Variação Genética/genética , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial , Humanos , Íntrons/genética , Mutação de Sentido Incorreto/genética , Fenótipo , Proteínas Proto-Oncogênicas c-retRESUMO
OBJECTIVE: To test the hypothesis that amantadine hydrochloride is a safe and effective treatment for behavioral disturbances--for example, hyperactivity and irritability--in children with autism. METHOD: Thirty-nine subjects (intent to treat; 5-19 years old; IQ > 35) had autism diagnosed according to DSM-IV and ICD-10 criteria using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-Generic. The Aberrant Behavior Checklist-Community Version (ABC-CV) and Clinical Global Impressions (CGI) scale were used as outcome variables. After a 1-week, single-blind placebo run-in, patients received a single daily dose of amantadine (2.5 mg/kg per day) or placebo for the next week, and then bid dosing (5.0 mg/kg per day) for the subsequent 3 weeks. RESULTS: When assessed on the basis of parent-rated ABC-CV ratings of irritability and hyperactivity, the mean placebo response rate was 37% versus amantadine at 47% (not significant). However, in the amantadine-treated group there were statistically significant improvements in absolute changes in clinician-rated ABC-CVs for hyperactivity (amantadine -6.4 versus placebo -2.1; p = .046) and inappropriate speech (-1.9 versus 0.4; p = .008). CGI scale ratings were higher in the amantadine group: 53% improved versus 25% (p = .076). Amantadine was well tolerated. CONCLUSIONS: Parents did not report statistically significant behavioral change with amantadine. However, clinician-rated improvements in behavioral ratings following treatment with amantadine suggest that further studies with this or other drugs acting on the glutamatergic system are warranted. The design of these and similar drug trials in children with autistic disorder must take into account the possibility of a large placebo response.
Assuntos
Amantadina/uso terapêutico , Transtorno Autístico/psicologia , Dopaminérgicos/uso terapêutico , Humor Irritável , Agitação Psicomotora/tratamento farmacológico , Agitação Psicomotora/etiologia , Adolescente , Adulto , Amantadina/administração & dosagem , Transtorno Autístico/diagnóstico , Criança , Pré-Escolar , Dopaminérgicos/administração & dosagem , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Agitação Psicomotora/diagnóstico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: The GDNF family receptor alpha (GFRalpha) proteins are extracellular cell surface bound molecules that act as adapters in binding of the GDNF family of soluble neurotrophic factors to the RET receptor. These molecules are essential for development of many neural crest derived cell types and the kidney. Mutations in RET and in two members of the GDNF ligand family are associated with Hirschsprung disease (HSCR), a congenital absence of the enteric ganglia. Members of the GFRalpha family are also candidates for HSCR mutations. One such gene is GFRalpha-3, which is expressed in the peripheral nervous system and developing nerves. OBJECTIVE: We have characterised the structure of the human GFRalpha-3 locus and investigated the gene for sequence variants in a panel of HSCR patients. METHODS: Long range PCR or subcloning of PAC clones was used to investigate GFRalpha-3 intron-exon boundaries. A combination of single strand conformation polymorphism (SSCP) analysis and direct sequencing was used to investigate GFRalpha-3 sequence variants. RESULTS: GFRalpha-3 spans eight coding exons and has a gene structure and organisation similar to that of GFRalpha-1. We identified three polymorphic variants in GFRalpha-3 in a normal control population, a subset of which also occurred in HSCR patients. We did not detect any sequence variants within the coding sequence of GFRalpha-3. We found a base substitution in the 5' UTR of GFRalpha-3, 15 base pairs upstream of the translation start site. A second substitution was identified in intron 4 (IVS4-30G>A) between the splice branch site and the splice acceptor site. The final variant was a 2 base pair insertion within the splice donor consensus sequence of exon 7 (IVS7+4ins GG). CONCLUSIONS: We did not detect any correlation between variants of GFRalpha-3 and the HSCR phenotype. Our data suggest that mutations of this gene are not a cause of HSCR.
Assuntos
Genes/genética , Doença de Hirschsprung/genética , Glicoproteínas de Membrana , Receptores de Superfície Celular/genética , Receptores de Fator de Crescimento Neural , Linhagem Celular , DNA/química , DNA/genética , Análise Mutacional de DNA , Éxons , Variação Genética , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial , Doença de Hirschsprung/patologia , Humanos , Íntrons , Mutagênese Insercional , Mutação , Mutação Puntual , Polimorfismo Conformacional de Fita Simples , Análise de Sequência de DNARESUMO
Schimke immunoosseous dysplasia (SID) is a rare, pleiotropic disorder compromising spondyloepiphyseal dysplasia, nephrotic syndrome, defective T-cell-mediated immunity, and vascular changes which can lead to cerebral infarcts. The cause is unknown but an autosomal recessive inheritance pattern has been suggested. Understanding of the clinical phenotype is evolving; however, the neurologic spectrum is not well known. We report on a 17-year-old woman who presented with behavior changes, developmental regression, and partial complex seizures in early childhood. Computed tomographic scan of the brain was normal at that time. Short stature and cognitive deficits became evident several months later. At 4 1/2 years, she developed nephrotic syndrome and later malignant hypertension. Recent magnetic resonance imaging of the brain showed focal encephalomalacia in the parietal regions and a magnetic resonance angiography documented narrowing of the middle cerebral arteries. A skeletal survey showed evidence of spondyloepiphyseal dysplasia. We have not been able to identify an immune defect. To our knowledge this is the first reported patient with SID, profound mental retardation, and a seizure disorder. This case supports the theory that an intrinsic vascular defect may be more important in the pathogenesis of SID than a T-cell-mediated immune deficit.
Assuntos
Anormalidades Múltiplas/patologia , Epilepsia/patologia , Deficiência Intelectual/patologia , Adolescente , Encéfalo/anatomia & histologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Radiografia , Coluna Vertebral/diagnóstico por imagem , SíndromeRESUMO
Inactivating mutations of the RET proto-oncogene and of one of its soluble ligand molecules, glial cell line derived neurotrophic factor (GDNF), have been found in a subset of patients with Hirschsprung disease (HSCR). However, the majority of HSCR mutations remain unidentified. As normal RET function requires a multicomponent ligand complex for activation, other members of the RET ligand complex are primary candidates for these mutations. We investigated the presence of mutations in another member of the RET signalling complex, GDNF family receptor alpha-1 (GFR alpha-1), in a panel of 269 independent cases of HSCR. We identified 10 polymorphisms at the GFR alpha-1 locus. Surprisingly, however, we did not identify any sequence variants in our HSCR population that were not also present in a normal control population. Our data suggest that mutations of the GFR alpha-1 gene are not a common aetiological event in HSCR.
Assuntos
Proteínas de Drosophila , Mutação em Linhagem Germinativa , Doença de Hirschsprung/genética , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Processamento Alternativo , Éxons , Variação Genética , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial , Humanos , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-retRESUMO
Implementation of PFC is considered a "rational" strategic choice in that it is thought to decrease the cost of providing health care while increasing the quality of services. Published research and evaluation studies that describe PFC are analyzed and the information is synthesized in hopes of discovering and describing commonalties among definitions, goals, and principles underlying PFC. The commonly accepted description of PFC is a model which "seeks to integrate the organization's values and culture with the operational excellence vision and processes to transform the institution into a customer-focused organization." Staff satisfaction is addressed by encouraging staff to plan and execute their clinical work in ways that are most responsive to patient needs. Grouping similar patients, bringing services closer to these patients, and appropriate cross-training of multidisciplinary care providers to enhance continuity of care are seen as the four most common elements described in most of the literature.
Assuntos
Enfermeiros Administradores/organização & administração , Supervisão de Enfermagem/organização & administração , Equipe de Assistência ao Paciente/organização & administração , Assistência Centrada no Paciente/organização & administração , Humanos , Modelos de Enfermagem , Enfermeiros Administradores/educação , Pesquisa em Administração de Enfermagem , Recursos Humanos de Enfermagem Hospitalar/organização & administração , Recursos Humanos de Enfermagem Hospitalar/psicologia , Desenvolvimento de ProgramasRESUMO
The mature mammalian kidney arises through a series of reciprocal inductive interactions between two different cell groups, the ureteric bud epithelium and the metanephric mesenchyme. The RET receptor tyrosine kinase is required for induction and development of the metanephric kidney. Differential splicing at the 3' end of RET results in transcripts encoding three isoforms that differ with respect to their C-terminal 9 (RET9), 51 (RET51) or 43 (RET43) amino acids. In vitro assays have identified differences in the abilities of the RET9 and RET51 isoforms to induce differentiation suggesting functional differences between these proteins. We examined the relative expression levels of the three RET 3' splicing variants in developing human kidney using semi-quantitative RT-PCR. We observed consistent expression of the RET9 and RET43 variants in kidney samples spanning 7.5 through 24 weeks gestation. At early gestational ages (7.5-8.5 weeks), RET51 expression was very low (+/-5%) compared to RET9; however, a rapid seven fold increase in expression was detected by 9 weeks. Our data suggest that RET51 may contribute to differentiation-related events occurring after 8.5 weeks gestation rather than to induction of the human kidney.
Assuntos
Processamento Alternativo , Proteínas de Drosophila , Rim/embriologia , Rim/metabolismo , Proteínas Proto-Oncogênicas/biossíntese , Receptores Proteína Tirosina Quinases/biossíntese , Humanos , Isomerismo , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-ret , RNA/metabolismo , RNA Mensageiro/metabolismo , Receptores Proteína Tirosina Quinases/genética , Transcrição GênicaRESUMO
GDNFR-alpha is a glycosyl-phosphotidylinositol-linked receptor for glial cell line-derived neurotrophic factor (GDNF). GDNF binds to GDNFR-alpha and this complex, in turn, is believed to interact with the RET receptor tyrosine kinase to effect downstream signalling. GDNFR-alpha belongs to a novel gene family without strong homology to known genes. Thus, little information has been available to help predict genomic structure or location of this gene. In this study, the genomic organization of human GDNFR-alpha was delineated through a combination of PAC clone characterization, long distance PCR and sequence analyses. Exon-intron boundaries were defined by comparing the size and sequence of the genomic PCR products to those predicted by the cDNA sequence. The human GDNFR-alpha gene comprises 9 exons. GDNFR-alpha PAC clones were used for FISH analysis to map this gene to 10q26.
Assuntos
Cromossomos Humanos Par 10 , Proteínas de Drosophila , Genoma Humano , Fatores de Crescimento Neural , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Sequência de Bases , Carcinoma Medular/genética , Mapeamento Cromossômico , Éxons , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial , Humanos , Hibridização in Situ Fluorescente , Íntrons , Proteínas do Tecido Nervoso/metabolismo , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-ret , Receptores Proteína Tirosina Quinases/metabolismo , Neoplasias da Glândula Tireoide/genética , Células Tumorais CultivadasRESUMO
Hirschsprung disease (HSCR) is a common congenital abnormality characterized by absence of the enteric ganglia in the hind gut. In 10-40% of HSCR cases, mutations of the RET receptor tyrosine kinase have been found. The recent identification of a multimeric RET ligand/receptor complex suggested that mutations of genes encoding other components of this complex might also occur in HSCR. To investigate this role, we examined the gene for glial cell line-derived neurotrophic factor (GDNF), the circulating ligand of the RET receptor complex, for mutations in a panel of sporadic and familial HSCR. We identified GDNF sequence variants in 2/36 HSCR patients. The first of these was a conservative change which did not affect the GDNF protein sequence. The second variant was a de novo missense mutation in a family with no history of HSCR and without mutation of the RET gene. Thus, our data are consistent with a causative role for GDNF mutations in some HSCR cases.
Assuntos
Proteínas de Drosophila , Doença de Hirschsprung/genética , Fatores de Crescimento Neural , Proteínas do Tecido Nervoso/genética , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial , Doença de Hirschsprung/metabolismo , Humanos , Ligantes , Mutação , Proteínas do Tecido Nervoso/metabolismo , Proteínas Proto-Oncogênicas c-retRESUMO
The cytoplasmic region of the common neurotrophin receptor (p75(NGFR)) (rat, human, chick) contains a putative membrane-associating domain implicated in intracellular signalling. A peptide (R3) identical to this domain (p75(NGFR) 367-379) and various analogues of this peptide displayed circular dichroism spectra in aqueous and non-polar environments identical to the amphiphilic tetradecapeptide mastoparan (MP) and were internalized by PC12 rat pheochromocytoma cells. The R3 peptide enhanced neurite growth in PC12 cells, embryo chick primary sensory neurons and fetal rat primary sensory neurons in vitro in the presence of sub-saturating concentrations of NGF. Peptide analogues of R3 not faithful to the distance and angular relationships of ionic groups and the putative amphiphilic structure of p75(NGFR)367-379 displayed reduced potency to enhance p75(NGFR) (PC12(nnr5)), had no influence on neurite growth. The R3 peptide had no effects on cell survival, cell binding or uptake of [125]NGF, affinity cross-linking of [125]NGF to p75(NGFR) or trkA monomers and homodimers, of NGF-mediated trkA monomer tyrosine phosphorylation. The studies implicate a role for a highly conserved motif of p75(NGFR) in the downstream modulation of NGF-mediated neurite growth.
Assuntos
Fatores de Crescimento Neural/fisiologia , Neuritos/fisiologia , Neurônios/ultraestrutura , Estrutura Terciária de Proteína , Receptores de Fator de Crescimento Neural/química , Sequência de Aminoácidos , Análise de Variância , Animais , Linhagem da Célula , Sobrevivência Celular/efeitos dos fármacos , Embrião de Galinha , Humanos , Magnésio/farmacologia , Dados de Sequência Molecular , Peso Molecular , Neuropeptídeos/farmacologia , Células PC12 , Ratos , Receptor de Fator de Crescimento Neural , Receptor trkA/biossíntese , Relação Estrutura-Atividade , Fatores de Virulência de Bordetella/farmacologiaRESUMO
The RET proto-oncogene, which encodes a receptor tyrosine kinase, displays multiple alternative splicing variants. Splicing of sequences 3' of exon 19 to generate several coding and untranslated region (UTR) sequences has been previously reported. We have sequenced the full length RET coding region and characterized the transcripts and 3' UTRs generated by alternative splicing of the RET 3' terminus. These analyses were performed using both RET cDNA cloned from a pheochromocytoma library and reverse transcriptase PCR products generated using RNA from a neuroblastoma cell line (LA-N-2). Three different carboxyl termini were identified. In addition to the nine and 51 terminal amino acid forms already known, we identified a third with 43 terminal amino acids predicted to encode a novel RET protein isoform. A total of 3621 base pairs of DNA 3' of exon 19, which spans the alternatively spliced exons and RET UTRs, was sequenced. Four polyadenylation sites were identified. The observed combinations of polyadenylation sites and 3' coding sequence suggest that RET transcripts with up to 10 different 3' sequences and up to 40 different full length RET transcripts may exist.
Assuntos
Processamento Alternativo , Proteínas de Drosophila , Poli A/genética , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/genética , Receptores Proteína Tirosina Quinases/genética , Neoplasias das Glândulas Suprarrenais/genética , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação , Clonagem Molecular , DNA Complementar/genética , Éxons , Humanos , Dados de Sequência Molecular , Neuroblastoma/genética , Feocromocitoma/genética , Reação em Cadeia da Polimerase , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-ret , Células Tumorais CultivadasRESUMO
"Based on 1979-1981 and 1989-1991 [U.S.] vital registration and 1980 and 1990 census data, we construct increment-decrement life tables for rural and urban males and females. The analysis is centered on 1980 and 1990 and describes urban-rural differences in patterns of mortality and nuptiality by age and sex. Our research updates an earlier study that described urban-rural mortality and marital transition patterns for Tennessee, 1970. The 1980 and 1990 findings parallel the 1970 results. Rural women and men have shorter life expectancies; higher infant mortality rates; younger median ages of entry into first marriage, divorce, and widowhood; a greater proportion of their cohorts ever marrying; lower probabilities of divorce; and higher probabilities of widowhood than urban women and men. However, there was a decline in urban-rural differences from 1970-1990. These changes suggest that urbanization, technological advances in communication and transportation, and the diffusion of urban lifestyles and values may have blurred the urban-rural distinction."
Assuntos
Fatores Etários , Economia , Geografia , Tábuas de Vida , Casamento , Mortalidade , População Rural , Fatores Sexuais , Tecnologia , População Urbana , Urbanização , América , Demografia , Países Desenvolvidos , América do Norte , População , Características da População , Dinâmica Populacional , Pesquisa , Estados UnidosRESUMO
Potential alpha-helical regions in cytoplasmic domains of the NGF/TNF receptor superfamily were searched to identify amphiphilic sequences favouring association with membrane surfaces, analogous to the predicted secondary structure of mastoparan (MP). Similar to MP, NGFR (rat, chick, human), human TNFR-1, and human 4-1BB have domains with putative surface membrane associating sequences. The circular dichroism spectra of mastoparan and a peptide homologous to the putative amphiphilic domain of NGFR were identical in an aqueous milieu, and both adopted an alpha-helical conformation in trifluoroethanol.
Assuntos
Citoplasma/química , Receptores de Fator de Crescimento Neural/química , Receptores do Fator de Necrose Tumoral/química , Sequência de Aminoácidos , Membrana Celular/química , Dicroísmo Circular , Peptídeos e Proteínas de Sinalização Intercelular , Dados de Sequência Molecular , Peptídeos/síntese química , Conformação Proteica , Estrutura Secundária de Proteína , Venenos de Vespas/químicaAssuntos
Frequência Cardíaca , Imageamento por Ressonância Magnética , Monitorização Fisiológica , Oximetria/instrumentação , Oxigênio/sangue , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Tecnologia de Fibra Óptica , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/instrumentação , Fibras ÓpticasRESUMO
The effects of the antihypertensive drug CI-926 on rat brain norepinephrine (NE), dopamine (DA), and serotonin (5-HT) turnover and its in vitro affinity for several receptors were investigated. CI-926 (3-30 mg/kg intraperitoneally, i.p.) caused a dose-dependent increase in the rate of brain stem NE synthesis and increased the decline in NE after inhibition of its synthesis by alpha-methyl-p-tyrosine. These findings indicated that CI-926 increased brain NE turnover, probably as a compensatory response to central adrenoceptor blockade based on its nanomolar affinity for alpha 1-adrenoceptors and micromolar affinity for alpha 2-adrenoceptors. CI-926 also increased the rate of DA synthesis and DA metabolite levels; this indicates an increase in DA turnover. The latter effect of CI-926 is attributed to a compensatory response to DA-2 receptor blockade because no affinity for DA-1 relative to DA-2 receptors was found and the effect was antagonized by the DA agonist pergolide. CI-926 decreased brain 5-HT turnover, as indicated by reduced concentrations of the 5-HT metabolite 5-hydroxyindoleacetic acid and a reduced rate of 5-HT synthesis, effects characteristic of centrally acting 5-HT agonists. Based on its affinity for 5-HT-1A receptors versus 5-HT-1B and 5-HT-2, the decrease in 5-HT synthesis and release is interpreted as evidence of 5-HT-1A receptor activation. These findings indicate that besides peripheral alpha 1-adrenergic blockade, an interference of CI-926 with central adrenergic and serotoninergic neurotransmission may contribute in part to an explanation of its antihypertensive properties.