RESUMO
Nonviral gene therapy approaches use a plasmid vector to express the desired transgene. We have systematically examined several regulatory elements within plasmid vectors that govern gene expression, e.g., the promoter, enhancer, intron, and polyadenylation signal, by constructing a series of plasmids that differed only in the particular sequence element being evaluated. Of the several promoters and polyadenylation signal sequences that were tested, the human cytomegalovirus (CMV) immediate early gene promoter and the addition of polyadenylation signal sequences from the bovine growth hormone (BGH) gene or rabbit beta-globin gene produced the highest levels of expression in vitro. The inclusion of a hybrid intron 3 to the promoter further increased expression 1.6-fold. The addition of a region of the CMV enhancer 5' to several weak promoters increased expression 8- to 67-fold, and co-transfection with a second plasmid encoding a chimeric transcription factor also enhanced expression. On the basis of these results, the CMV promoter, the hybrid intron, and the BGH polyadenylation signal were selected for consistent high level expression in vitro and in the mouse lung. However, expression was transient, with greater than 60% loss of activity in the first 7 days. This transient expression was not specific to CMV promoter-containing plasmids, because plasmids containing other heterologous promoters showed a similar profile of transient expression in vivo. These comparative analyses begin to provide a basis for the development of optimized expression plasmids for gene therapy of lung diseases.
Assuntos
Citomegalovirus/genética , Elementos Facilitadores Genéticos/fisiologia , Regulação da Expressão Gênica , Técnicas de Transferência de Genes , Genes Precoces/genética , Vetores Genéticos/genética , Pulmão , Transgenes/genética , Animais , Bovinos , Células Cultivadas , Cloranfenicol O-Acetiltransferase/genética , Cloranfenicol O-Acetiltransferase/metabolismo , Elementos Facilitadores Genéticos/genética , Genes Reporter , Humanos , Íntrons , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Poli A/metabolismo , Regiões Promotoras Genéticas , CoelhosRESUMO
This article reviews the current classification of anxiety disorders and the frequency of these disorders in older adults. General treatment principles are discussed, and an overview of anxiolytic medications is presented. Use of these anxiolytic agents in specific disorders is then discussed, followed by a brief review of non-pharmacologic treatment approaches to anxiety disorders.
Assuntos
Ansiolíticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Fatores Etários , Idoso , HumanosAssuntos
Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/efeitos adversos , Indanos/efeitos adversos , Transtornos Mentais/induzido quimicamente , Piperidinas/efeitos adversos , Idoso , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/psicologia , Inibidores da Colinesterase/uso terapêutico , Donepezila , Humanos , Indanos/uso terapêutico , Transtornos Mentais/psicologia , Piperidinas/uso terapêuticoRESUMO
For a significant number of retired older adults (aged 65+), gambling has become a new form of recreation and entertainment. While prevalence studies have examined the incidence of problem gambling in other age groups, little research attention has been paid to the impact of gambling on older adults since the increase in availability and accessibility of legalized gambling within the last ten years. This study investigated the prevalence of problem gambling behaviors (SOGS-R), depression (GDS-15), levels of life satisfaction (SWLS), and motivations for gambling among older adults. A total of 315 older adults completed the study questionnaire and were grouped and analyzed according to those sampled from gambling venues and those from within the community. Results of the study found the most frequent accession and spending on several types of gambling occurred among older adults who were sampled at gambling venues. Older adults who were sampled at gambling venues were also found more likely to have higher levels of disordered gambling than older adults from the community, as measured by the SOGS-R. Relaxation, boredom, passing time, and getting away for the day were also the most likely reported motivations for the older adults who were gambling patrons. These findings provide an initial profile of older adults and their attitudes, motivations and gambling behaviors.
RESUMO
A significant number of senior citizens (aged 65+) spend their leisure time in gambling casinos in this country. For some older adults eager for a stimulating social outlet, casino gambling can become a virulent and destructive addiction. While prevalence studies have examined the incidence of problem gambling in other age groups, little attention has been paid to the impact of casino gambling on older adults. This study investigated the prevalence of casino gambling as a social activity for active senior citizens (aged 65+). Activity directors from residential and assisted-care facilities as well as from senior and retirement centers completed mailed surveys of eleven different types of social activities available to older adults. Results of the survey of activity directors found bingo the most highly frequented on-location-type social activity and casino gambling the most highly frequented day-trip-type social activity for 6,957 active senior citizens represented in the activity directors' survey. On average, 16 percent of the senior citizens were reported by the activity directors to have taken part in facility-sponsored trips to the casino on at least a once-a-month basis. In addition, the casinos themselves had offered additional gambling day-trips to 66 percent of the facilities, which were accepted in 58 percent of the cases. These findings suggest the need for greater awareness of the impact casino gambling may have on senior citizens in this country.
Assuntos
Idoso/estatística & dados numéricos , Jogo de Azar , Atividades de Lazer/classificação , Idoso de 80 Anos ou mais , Humanos , Nebraska , Prevalência , Inquéritos e QuestionáriosRESUMO
The case of a 77-year-old woman first diagnosed with kleptomania is presented to indicate a possible late-onset course of this disorder. Particularly striking about this patient's history of shoplifting behaviors was the absence of an onset prior to the age of 73. Her pattern of stealing did not begin at an early age, and was not sporadic or episodic over the course of several years. The treatment course and patient outcome are discussed in light of DSM-IV diagnostic criteria.
Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta/psicologia , Fatores Etários , Idoso , Transtornos Cognitivos/diagnóstico , Terapia Cognitivo-Comportamental , Transtornos Disruptivos, de Controle do Impulso e da Conduta/terapia , Feminino , Humanos , MMPI , Testes Neuropsicológicos , Transtornos da Personalidade/diagnósticoRESUMO
The peptide-N4-(N-acetyl-beta-D-glucosaminyl) asparagine amidase F (PNGase F) gene from Flavobacterium meningosepticum was cloned into a high copy number Escherichia coli plasmid. Levels of PNGase F activity produced in cultures of the recombinant strain were up to 100-fold higher than those obtained in cultures of F. meningosepticum. The complete PNGase F gene sequence was determined. Comparison of the predicted amino acid sequence of pre-PNGase F to the N-terminal sequence of the native mature enzyme indicates that the protein is synthesized with a 40-amino acid signal sequence that is removed during secretion in F. meningosepticum. The recombinant PNGase F produced in E. coli is a mixture of products comprised predominantly of two proteins with molecular masses of 36.3 and 36.6 kDa. These proteins have a higher apparent molecular mass than the 34.7-kDa native enzyme. N-terminal amino acid sequencing demonstrated that these higher molecular mass products result from cleavage of the pre-PNGase F in E. coli upstream of the native N terminus. The PNGase F gene was engineered to encode a preenzyme that was processed in E. coli to give an N terminus identical to that of the native enzyme. Purified preparations of this form of recombinant PNGase F were shown to be suitable for glycoprotein analyses since they possess no detectable endo-beta-N-acetylglucosaminidase F, exoglycosidase, or protease activity.