RESUMO
AIM: The objective was to assess the effect of three different surgical treatments for T1 rectal tumours, radical resection (RR), open local excision (open LE) and laparoscopic local excision (laparoscopic LE), on overall survival (OS). METHODS: Adults from the National Cancer Database (2008-2016) with a diagnosis of T1 rectal cancer were stratified by treatment type (LE vs RR). We assumed that laparoscopic LE equates to transanal minimally invasive surgery (TAMIS) or transanal endoscopic microsurgery. The primary outcome was 5-year OS. Subgroup analyses of the LE group stratified by time period [2008-2010 (before TAMIS) vs 2011-2016 (after TAMIS)] and approach (laparoscopic vs open) were performed. RESULTS: Among 10 053 patients, 6623 (65.88%) underwent LE (74.33% laparoscopic LE vs 25.67% open LE) and 3430 (34.12%) RR. The use of LE increased from 52.69% in 2008 to 69.47% in 2016, whereas RR decreased (P < 0.001). In unadjusted analysis, there was no significant difference in 5-year OS between the LE and RR groups (P = 0.639) and between the two LE time periods (P = 0.509), which was consistent with the adjusted analysis (LE vs RR, hazard ratio 1.05, 95% CI 0.92-1.20, P = 0.468; 2008-2010 LE vs 2011-2016 LE, hazard ratio 1.09, 95% CI 0.92-1.29, P = 0.321). Laparoscopic LE was associated with improved OS in the unadjusted analysis only (P = 0.006), compared to the open LE group (hazard ratio 0.94, 95% CI 0.78-1.12, P = 0.495). CONCLUSIONS: This study supports the use of a LE approach for T1 rectal tumours as a strategy to reduce surgical morbidity without compromising survival.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Laparoscopia , Neoplasias Retais , Microcirurgia Endoscópica Transanal , Cirurgia Endoscópica Transanal , Adulto , Humanos , Neoplasias Retais/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: The quality of life (QoL) of informal caregivers of people with Parkinson's disease (PD) (PwP) can be affected by the caring role. Because of cognitive symptoms and diminished activities of daily living, in addition to the management of motor symptoms, carers of PwP and cognitive impairment may experience increased levels of burden and poorer QoL compared with carers of PwP without cognitive impairment. This study aimed to investigate the impact of cognitive impairment in PD upon QoL of carers. METHODS: Approximately 36 months after diagnosis, 66 dyadic couples of PwP and carers completed assessments. PwP completed a schedule of neuropsychological assessments and QoL measures; carers of PwP completed demographic questionnaires and assessments of QoL. Factor scores of attention, memory/executive function and global cognition, as derived by principal component analysis, were used to evaluate cognitive domains. RESULTS: Hierarchical regression analysis found lower Montreal Cognitive Assessment was a significant independent predictor of poorer carer QoL, in addition to number of hours spent caregiving, carer depression and PD motor severity. Attentional deficits accounted for the largest proportion of variance of carer QoL. Carers of PwP and dementia (n = 9) had significantly poorer QoL scores compared with PwP and mild cognitive impairment (n = 18) or normal cognition (n = 39) carers (p < 0.01). CONCLUSIONS: Attentional deficits were the strongest predictor of carer QoL compared with other cognitive predictors. Carers for those with PD dementia reported the poorest QoL. Interventions such as respite or cognitive behavioural therapy to improve mood and self-efficacy in carers may improve carer QoL. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd.
Assuntos
Transtornos Cognitivos , Doença de Parkinson/psicologia , Qualidade de Vida , Atividades Cotidianas/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Qualidade de Vida/psicologia , Análise de Regressão , Inquéritos e QuestionáriosRESUMO
AIMS: The growing interest of governments and industry in developing healthy and natural alternative foods and beverages that will fulfil the consumer drive towards a healthy lifestyle and clean-label, natural diet has led to an increase in traditional lactic acid bacteria fermentation research. In particular, this research aims to address the organoleptic modulation of beverages using in situ-produced bacterial polysaccharides. METHODS AND RESULTS: Weissella cibaria MG1 is capable of producing exopolysaccharides (dextran) and oligosaccharides (glucooligosaccharides) during sucrose-supplemented barley-malt-derived wort fermentation. Up to 36·4 g l(-1) of dextran was produced in an optimized system, which improved the rheological profile of the resulting fermentate. Additionally, small amounts of organic acids were formed, and ethanol remained below 0·5% (v/v), the threshold volume for a potential health claim designation. CONCLUSIONS: The results suggest that the cereal fermentate produced by W. cibaria MG1 could be potentially used for the production of a range of novel, nutritious and functional beverages. SIGNIFICANCE AND IMPACT OF THE STUDY: Using conventional raw materials and traditional processes, novel LAB-fermented beverages can be produced representing an innovative mechanism towards fulfilling the aim to decrease government and personal costs as well as potentially ameliorating consumer lifestyle regarding dietary-related disease.
RESUMO
BACKGROUND AND AIMS: Ascertainment bias (AB) indicates a bias of an evaluation centre in estimating the prevalence/incidence of a disease due to the specific expertise of the centre. The aim of our study was to evaluate classification of different types of dementia in new cases appearing in secondary and tertiary centres, in order to evidence possible occurrence of AB in the various (secondary to tertiary) dementia centres. METHODS: To assess the mechanism of AB, the rates of new cases of the different forms of dementia reported by different centres were compared. The centres involved in the study were 11 hospital-based centres including a tertiary centre, located in the University Department of Clinical Neurology. The tertiary centre is endowed with state-of-the-art diagnostic facilities and its scientific production is prominently focused on dementia with Lewy bodies (DLB) thus suggesting the possible occurrence of a bias. Four main categories of dementia were identified: Alzheimer's disease (AD), DLB, fronto-temporal dementia (FTD), vascular dementia (VaD), with other forms in a category apart. The classification rate of new cases of dementia in the tertiary centre was compared with rates reported by secondary centres and rates of recoding were calculated during a follow-up of 2 years. RESULTS: The study classified 2,042 newly diagnosed cases of dementia in a population of 1,370,000 inhabitants of which 315,000 were older than 65. AD was categorized in 48-52 % of cases, DLB in 25-28 %, FTD in 2-4 % and VaD in 17-28 %. During the 2-year follow-up the diagnosis was re-classified in 40 patients (3 %). The rate of recoding was 5 % in the tertiary centre, 2-8 % in referrals from secondary to tertiary centre, 2-10 % in recodings performed in secondary centres and addressed to tertiary centre. Recoding or percentages of new cases of AD or DLB were not different in the comparison between secondary or between secondary and tertiary centres. FTD and VaD were instead significantly recoded. CONCLUSION: The results of the study suggest that in a homogeneous area, AB is not interfering with diagnosis of AD or DLB.
Assuntos
Viés , Competência Clínica , Demência/diagnóstico , Demência/epidemiologia , Hospitais/estatística & dados numéricos , Centros de Atenção Terciária/estatística & dados numéricos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Demência/classificação , Diagnóstico Diferencial , Demência Frontotemporal/diagnóstico , Demência Frontotemporal/epidemiologia , Humanos , Itália/epidemiologia , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/epidemiologia , Imageamento por Ressonância Magnética , Prevalência , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Dementia with Lewy bodies (DLB) and dementia in Parkinson's disease (PDD) are recognised to be under-recognised in clinical practice in the UK, with only one third to a half of expected cases diagnosed. We aimed to assess whether clinical diagnostic rates could be increased by the introduction of a structured assessment toolkit for clinicians. METHODS: We established baseline diagnostic rates for DLB and PDD in four memory clinics and three movement disorder/Parkinson's disease (PD) clinics in two separate geographical regions in the UK. An assessment toolkit specifically developed to assist with the recognition and diagnosis of DLB and PDD was then introduced to the same clinical teams and diagnostic rates for DLB and PDD were reassessed. For assessing DLB diagnosis, a total of 3820 case notes were reviewed before the introduction of the toolkit, and 2061 case notes reviewed after its introduction. For PDD diagnosis, a total of 1797 case notes were reviewed before the introduction of the toolkit and 3405 case notes after it. Mean values and proportions were analysed using Student's t test for independent samples and χ2 test, respectively. RESULTS: DLB was diagnosed in 4.6% of dementia cases prior to the introduction of the toolkit, and 6.2% of dementia cases afterwards, an absolute rise of 1.6%, equal to a 35% increase in the number of DLB cases diagnosed when using the toolkit (χ2 = 4.2, P = 0.041). The number of PD patients diagnosed with PDD was not found overall to be significantly different when using the toolkit: 9.6% of PD cases before and 8.2% of cases after its introduction (χ2 = 1.8, P = 0.18), though the ages of PD patients assessed after the toolkit's introduction were lower (73.9 years vs 80.0 years, t = 19.2, p < 0.001). CONCLUSION: Introduction of the assessment toolkit was associated with a significant increase in the rate of DLB diagnosis, suggesting that a structured means of assessing symptoms and clinical features associated with DLB can assist clinicians in recognising cases. The assessment toolkit did not alter the overall rate of PDD diagnosis, suggesting that alternate means may be required to improve the rate of diagnosis of dementia in Parkinson's disease.
Assuntos
Doença por Corpos de Lewy , Doença de Parkinson , Idoso , Humanos , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/epidemiologia , Memória , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologiaRESUMO
Mutations in the Leucine Rich Repeat Kinase 2 (LRRK2) gene, first described in 2004 have now emerged as the most important genetic finding in both autosomal dominant and sporadic Parkinson's disease (PD). While a formidable research effort has ensued since the initial gene discovery, little is known of either the normal or the pathological role of LRRK2. We have created lines of mice that express human wild-type (hWT) or G2019S Lrrk2 via bacterial artificial chromosome (BAC) transgenesis. In vivo analysis of the dopaminergic system revealed abnormal dopamine neurotransmission in both hWT and G2019S transgenic mice evidenced by a decrease in extra-cellular dopamine levels, which was detected without pharmacological manipulation. Immunopathological analysis revealed changes in localization and increased phosphorylation of microtubule binding protein tau in G2019S mice. Quantitative biochemical analysis confirmed the presence of differential phospho-tau species in G2019S mice but surprisingly, upon dephosphorylation the tau isoform banding pattern in G2019S mice remained altered. This suggests that other post-translational modifications of tau occur in G2019S mice. We hypothesize that Lrrk2 may impact on tau processing which subsequently leads to increased phosphorylation. Our models will be useful for further understanding of the mechanistic actions of LRRK2 and future therapeutic screening.
Assuntos
Encéfalo/metabolismo , Proteínas Serina-Treonina Quinases/genética , Transmissão Sináptica/fisiologia , Proteínas tau/metabolismo , Animais , Autorradiografia , Cromatografia Líquida de Alta Pressão , Cromossomos Artificiais Bacterianos , Dopamina/metabolismo , Humanos , Immunoblotting , Hibridização In Situ , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Camundongos , Camundongos Transgênicos , Microdiálise , Fosforilação , Processamento de Proteína Pós-Traducional , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
AIMS: To assess the availability and types of psychological services for people with diabetes in the UK, compliance with national guidelines and skills of the diabetes team in, and attitudes towards, psychological aspects of diabetes management. METHODS: Postal questionnaires to team leads (doctor and nurse) of all UK diabetes centres (n = 464) followed by semi-structured telephone interviews of expert providers of psychological services identified by team leads. RESULTS: Two hundred and sixty-seven centres (58%) returned postal questionnaires; 66 (25%) identified a named expert provider of psychological services, of whom 53 (80%) were interviewed by telephone. Less than one-third (n = 84) of responding centres had access to specialist psychological services and availability varied across the four UK nations (P = 0.02). Over two-thirds (n = 182) of centres had not implemented the majority of national guidelines and only 2.6% met all guidelines. Psychological input into teams was associated with improved training in psychological issues for team members (P < 0.001), perception of better skills in managing more complex psychological issues (P < or = 0.01) and increased likelihood of having psychological care pathways (P < or = 0.05). Most (81%) expert providers interviewed by telephone were under-resourced to meet the psychological needs of their population. CONCLUSIONS: Expert psychological support is not available to the majority of diabetes centres and significant geographical variation indicates inequity of service provision. Only a minority of centres meet national guidelines. Skills and services within diabetes teams vary widely and are positively influenced by the presence of expert providers of psychological care. Lack of resources are a barrier to service provision.
Assuntos
Diabetes Mellitus/psicologia , Aconselhamento/organização & administração , Estudos Transversais , Atenção à Saúde , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Masculino , Guias de Prática Clínica como Assunto , Inquéritos e QuestionáriosRESUMO
Research into hallucinations typically regards them as single sensory or unimodal experiences leading to a comparative neglect of co-occurring multi-sensory hallucinations (MSH). People with psychosis who have visual hallucinations (VH) report high rates of hallucinations in other senses (auditory, olfactory, tactile). However, it is not known if this is similar to other groups who report VH. Consequently, this study explored MSH in four different patient groups who all had current VH. Archival data from standardised assessments of visual hallucinations in people with psychosis (nâ¯=â¯22), eye disease (ED) (nâ¯=â¯82), Lewy body Dementia (LBD) (nâ¯=â¯41), and Parkinson's disease (PD) (nâ¯=â¯41) determined the presence of MSH. People with psychosis and visual hallucinations reported significantly higher rates of MSH (auditory, 73%; tactile, 82%; olfactory/gustatory hallucinations, 27%) than the LBD group (auditory, 21%; tactile, 28%; olfactory/gustatory, 6%), ED (auditory, 1%; tactile, 11%; olfactory/gustatory, 0%) and PD patients (auditory, 3%; tactile, 8%; olfactory/gustatory, 3%). Regardless of diagnostic grouping, participants with MSH reported greater conviction that the VH were real, and reported greater distress. People with psychosis with VH report high rates of MSH unlike groups of older adults with VH. These between group differences in MSH prevalence have implications for clinical practice and theory.
Assuntos
Oftalmopatias/fisiopatologia , Alucinações/fisiopatologia , Doença por Corpos de Lewy/fisiopatologia , Doença de Parkinson/fisiopatologia , Transtornos Psicóticos/fisiopatologia , Percepção Visual/fisiologia , Idoso , Oftalmopatias/complicações , Feminino , Alucinações/etiologia , Humanos , Doença por Corpos de Lewy/complicações , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Transtornos Psicóticos/complicaçõesRESUMO
BACKGROUND: Postural instability gait difficulty (PIGD) motor phenotype in Parkinson's disease (PD) is associated with a faster rate of cognitive decline than in tremor dominant cases and may be a risk factor for incident dementia. People with PD display attentional deficits; however, it is not clear whether attentional deficits in patients with non-demented PD are associated with (i) PIGD phenotype and/or (ii) subsequent cognitive decline. AIMS: (i) To examine rates of cognitive decline (Mini-Mental State Examination (MMSE) and Cambridge Cognitive Examination (CAMCOG)) over 3 years in subjects with non-demented PD aged over 65 years, (ii) using Cognitive Drug Research computerised assessment test battery, determine the rate of change in power of attention (PoA) scores over time (sum of mean choice reaction time, simple reaction time and digit vigilance reaction time scores), (iii) determine whether the PIGD phenotype is associated with changes in PoA and (iv) establish whether baseline PoA is associated with subsequent cognitive decline. RESULTS: 14 subjects (38%) were classified as PIGD motor phenotype at baseline. Cognitive decline was greater in PIGD compared with non-PIGD subjects (p < or = 0.02). PIGD phenotype was not associated with baseline PoA score although it was associated with subsequent worsening in PoA (mean PoA increase/year: non-PIGD subjects 11.4 ms; PIGD subjects 244.0 ms; p = 0.01). Higher baseline PoA scores were associated with greater cognitive decline (MMSE, p = 0.03; CAMCOG, p = 0.05) independent of PIGD status. CONCLUSION: PIGD phenotype and attention deficits are independently associated with a greater rate of cognitive decline in patients with non-demented PD. We propose that subtle attentional deficits in patients with non-demented PD predict subsequent cognitive impairment.
Assuntos
Transtornos Cognitivos/diagnóstico , Demência/complicações , Doença de Parkinson/diagnóstico , Idoso , Atenção , Cognição , Transtornos Cognitivos/patologia , Demência/diagnóstico , Progressão da Doença , Feminino , Transtornos Neurológicos da Marcha/complicações , Transtornos Neurológicos da Marcha/diagnóstico , Humanos , Masculino , Testes Neuropsicológicos , Doença de Parkinson/patologia , Fenótipo , Análise de Regressão , Tremor/complicações , Tremor/diagnósticoRESUMO
Pathogenic substitutions in leucine-rich repeat kinase 2 (LRRK2, Lrrk2) have been genetically linked to familial, late-onset Parkinsonism. End-stage disease is predominantly associated with nigral neuronal loss and Lewy body pathology, but patients may have gliosis, tau or ubiquitin inclusions (pleomorphic pathology). The anatomical distribution of Lrrk2 protein may provide insight into its function in health and neurodegeneration, thus we performed a comparative study with 'in-house' and commercially available Lrrk2 antibodies using brain tissue from wild type and human Lrrk2 transgenic bacterial artificial chromosome (BAC) mice, and from diffuse Lewy body disease (DLBD) patients. Lrrk2 protein was ubiquitously expressed and relatively abundant in most brain regions, including the substantia nigra, thalamus and striatum. Lrrk2 was not a major component of Lewy body or neuritic pathology associated with Parkinson's disease. However, selective loss of dopaminergic neurons in Lrrk2-associated Parkinsonism argues the protein may have regional-specific interactions. Lrrk2 immunohistochemical staining was present in the subventricular zone, a region containing stem cells that give rise to both neurons and glia. A role for Lrrk2 in neurogenesis might provide further insight into the aberrant role of mutant protein in age-associated neurodegeneration with pleomorphic pathology.
Assuntos
Encéfalo/enzimologia , Expressão Gênica/fisiologia , Doença por Corpos de Lewy/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Autorradiografia , Encéfalo/patologia , Linhagem Celular Transformada , Cromossomos Artificiais Bacterianos/fisiologia , Expressão Gênica/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Doença por Corpos de Lewy/patologia , Camundongos , Camundongos Transgênicos , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Proteínas Serina-Treonina Quinases/genética , Ácidos Siálicos/metabolismo , Transfecção/métodos , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
We present a case of a chronic recurrent rectovaginal fistula that initially arose from complications of haemorrhoid surgery and had failed multiple prior surgical repairs. The fistula was successfully managed using viable cryopreserved placental tissue.
Assuntos
Placenta/transplante , Fístula Retovaginal , Doença Crônica , Criopreservação , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Fístula Retovaginal/patologia , Fístula Retovaginal/fisiopatologia , Fístula Retovaginal/cirurgia , CicatrizaçãoRESUMO
We present a rare case of an arterioportal fistula that formed between the superior mesenteric artery and portal vein 30 days following a pancreaticoduodenectomy, which was successfully managed with endovascular procedures.
Assuntos
Fístula Arteriovenosa , Procedimentos Endovasculares/métodos , Artéria Mesentérica Superior , Pancreaticoduodenectomia/efeitos adversos , Veia Porta , Humanos , Artéria Mesentérica Superior/diagnóstico por imagem , Artéria Mesentérica Superior/cirurgia , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Complicações Pós-OperatóriasRESUMO
Infection by human immunodeficiency virus type 1 (HIV-1), the etiologic agent of the acquired immunodeficiency syndrome (AIDS), is often complicated with a high incidence of neurologic disorders. It is believed that HIV-1, in addition to infecting both macroglial and microglial cells, may influence the expression of several strategic genes of uninfected neighboring or latently infected brain cells. It is suspected that the viral-encoded transregulatory protein, Tat, facilitates cross-communications between these cells. In support of this concept, earlier studies demonstrated that Tat is released from the infected cells, and has the capacity to be taken up by the uninfected cells and exert its biological activity on the responsive gene. Recent studies in several laboratories suggest the involvement of Tat in altering the expression of a limited number of cellular regulatory factors which, in turn, may mediate the altered physiology of the cells. In this communication, we demonstrate the ability of the HIV-1 Tat protein to increase expression of transforming growth factor beta 1 (TGF-beta 1), a cytokine with potent immunosuppressive activity, in human astrocytic glial cells. Implications of the Tat-mediated induction of TGF-beta 1 expression and cytokine involvement in the regulation of immune response and central nervous system (CNS) pathology are discussed.
Assuntos
Astrócitos/efeitos dos fármacos , Produtos do Gene tat/farmacologia , HIV-1 , Regiões Promotoras Genéticas , Fator de Crescimento Transformador beta/genética , Astrócitos/metabolismo , Mapeamento Cromossômico , Expressão Gênica/efeitos dos fármacos , Células HeLa , Humanos , RNA Mensageiro/análise , Ativação Transcricional , Células Tumorais Cultivadas , Produtos do Gene tat do Vírus da Imunodeficiência HumanaRESUMO
The Human Immunodeficiency Virus type 1 (HIV-1) Tat protein is a potent activator of transcription directed by the long terminal repeat (LTR), an essential step in the life-cycle of HIV-1. While interaction of Tat with an RNA element encoded by downstream LTR sequences (termed TAR) is commonly considered essential to activation, numerous recent reports have implicated upstream transcription elements within the LTR as participants in mediating this activation. We have recently demonstrated that Tat activation occurs independent of the TAR element in certain cells derived from the central nervous system (CNS), and that this activation is mediated by the kappa B domain of the LTR. Further, CNS-derived cells were found to contain kappa B-binding activity capable of both interacting with Tat and activating LTR transcription in vitro. The present study demonstrates that the kappa B-binding transcription factor derived from CNS cells consists of a component indistinguishable from prototypical Nuclear Factor-kappa B (NF-kappa B) (in size, mobility on native gel, kinetics of activation and cognate binding sequence) as well as a supershifting component that is dissociable under certain conditions. The supershifting activity is found to stabilize binding of the presumed NF-kappa B to DNA. Further, only the form of NF-kappa B which is associated with this supershifting activity is capable of binding Tat. We hypothesize a model in which Tat utilizes this interaction to activate HIV-1 through the NF-kappa B domain of the LTR in circumstances where TAR is absent. This model has implications with respect to the ability of Tat to alter cellular gene expression and perhaps contribute to the array of problems seen in HIV-1 infection such as altered immune status, CNS toxicity, and the formation of tumors.
Assuntos
Astrócitos/metabolismo , Produtos do Gene tat/fisiologia , HIV-1/fisiologia , NF-kappa B/metabolismo , Sequência de Bases , Eletroforese em Gel Bidimensional , Modelos Genéticos , Dados de Sequência Molecular , Sequências Repetitivas de Ácido Nucleico , Ativação Transcricional , Produtos do Gene tat do Vírus da Imunodeficiência HumanaRESUMO
We compared the ability of HIV-1 tat protein and JCV T-antigen in inducing transcription from the JCV late promoter, JCVL. A JCVL promoter-chloramphenicol acetyltransferase plasmid (pJCL-CAT) was transfected into human glial cells alone or together with plasmids producing T-antigen and tat protein. CAT enzyme activity obtained from the transfected cells indicated that both JCV T-antigen and HIV-1 tat proteins stimulated JCV late gene expression. However, the level of induction mediated by tat protein was significantly higher than that obtained with T-antigen. Moreover, in contrast to JCV T-antigen, tat stimulated JCVL-promoter activity over a narrow range of ptat expressor plasmid concentration. Co-transfection of both T-antigen and tat plasmids at optimal concentrations resulted in greater than additive CAT activity from the JCVL promoter. This synergism suggests that the two activator proteins utilize alternative mechanisms to exert their effects. Using deletion mutations from the 5' end of the JCVL promoter, we demonstrated that different regions within the JCV enhancer/promoter are important for T-antigen and tat induction, implying that these activators function through distinct targets to increase JCVL promoter activity.
Assuntos
Antígenos Transformantes de Poliomavirus/fisiologia , Regulação Viral da Expressão Gênica/fisiologia , Produtos do Gene tat/fisiologia , HIV-1/genética , Vírus JC/imunologia , Regiões Promotoras Genéticas/genética , Sequência de Bases , Cloranfenicol O-Acetiltransferase/genética , Cloranfenicol O-Acetiltransferase/metabolismo , Deleção Cromossômica , Produtos do Gene tat/genética , Humanos , Dados de Sequência Molecular , Mutação/genética , Neuroglia/enzimologia , Neuroglia/fisiologia , Plasmídeos , Regiões Promotoras Genéticas/efeitos dos fármacos , Regiões Promotoras Genéticas/fisiologia , Transcrição Gênica/efeitos dos fármacos , Transcrição Gênica/fisiologia , Transfecção , Produtos do Gene tat do Vírus da Imunodeficiência HumanaRESUMO
Localised alterations in cytoplasmic Ca(2+) levels are an integral part of the response of eukaryotic cells to a plethora of external stimuli. Due to the large size of nuclear pores, it has generally been assumed that intranuclear Ca(2+) levels reflect the prevailing cytoplasmic Ca(2+) levels. Using nuclei prepared from carrot (Daucus carota L.) cells, we now show that Ca(2+) can be transported across nuclear membranes in an ATP-dependent manner and that over 95% of Ca(2+) is accumulated into a pool releasable by the Ca(2+) ionophore A.23187. ATP-dependent nuclear Ca(2+) uptake did not occur in the presence of ADP or ADPgammaS and was abolished by orthovanadate. Confocal microscopy of nuclei loaded with dextran-linked Indo-1 showed that the initial ATP-induced rise in [Ca(2+)] occurs in the nuclear periphery. The occurrence of ATP-dependent Ca(2+) uptake in plant nuclei suggests that alterations of intranuclear Ca(2+) levels may occur independently of cytoplasmic [Ca(2+)] changes.
Assuntos
Trifosfato de Adenosina/metabolismo , Cálcio/metabolismo , Núcleo Celular/metabolismo , Plantas/metabolismo , Transporte Biológico Ativo , Citoplasma/metabolismo , Daucus carota/metabolismo , Cinética , Microscopia Confocal , Membrana Nuclear/metabolismoRESUMO
OBJECTIVE: To characterize the development of ipsilateral corticospinal projections from birth and compare to 1) development of contralateral projections in the same subjects and 2) ipsilateral corticospinal projections in subjects with unilateral lesions of the corticospinal system acquired perinatally or in adulthood. METHOD: Transcranial magnetic stimulation excited the motor cortex, and responses were recorded bilaterally in pectoralis major, biceps brachii, and the first dorsal interosseus muscles. Subjects studied included 9 neonates recruited at birth, studied longitudinally for 2 years; 85 healthy subjects aged from birth to adulthood; 10 subjects with hemiplegic cerebral palsy; and 8 with hemiplegia after stroke. RESULTS: In neonates, ipsilateral responses had significantly shorter onsets than contralateral responses but similar thresholds and amplitudes. Thresholds within both pathways increased in the first 3 months. Differential development was present from 3 months so that by 18 months ipsilateral responses were significantly smaller and had significantly higher thresholds and longer onset latencies than contralateral responses. A similar pattern of smaller and later ipsilateral responses was observed after transcranial magnetic stimulation of the intact cortex in subjects with stroke. In contrast, subjects with hemiplegic cerebral palsy had ipsilateral responses with onsets, thresholds and amplitudes similar to those of contralateral responses. Significant branching of contralateral corticospinal axons from the intact motor cortex was excluded by cross-correlation analysis. CONCLUSIONS: These data, together with previously published anatomic and radiologic studies, are consistent with activity-dependent corticospinal axonal withdrawal during development and maintenance of increased corticomotoneuronal projections from the intact hemisphere after unilateral perinatal lesions.
Assuntos
Tratos Piramidais/crescimento & desenvolvimento , Tratos Piramidais/fisiologia , Adolescente , Adulto , Axônios/fisiologia , Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/fisiologia , Paralisia Cerebral/fisiopatologia , Criança , Pré-Escolar , Estudos Transversais , Estimulação Elétrica , Eletromiografia , Feminino , Lateralidade Funcional/fisiologia , Hemiplegia/fisiopatologia , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Magnetismo , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/inervação , Músculo Esquelético/fisiologia , Reflexo/fisiologia , Acidente Vascular Cerebral/fisiopatologiaRESUMO
An 81-year-old woman had chills, fever, nausea, vomiting, and epigastric pain. On day 3 she had hematuria and was treated with trimethoprim-sulfamethoxazole. On day 5 she had a cough, hypotension, anemia, azotemia, and elevated hepatic enzyme levels. Her condition deteriorated with thrombocytopenia, anuria requiring dialysis, edema, and hypoalbuminemia. Treatment with chloramphenicol and doxycycline was started on day 10. By day 11, she was in hypotensive shock; on day 12 she had seizures and died. Murine typhus was diagnosed by demonstration of antibodies to Rickettsia typhi by indirect immunofluorescence. Necropsy revealed interstitial pneumonia, pulmonary edema, hyaline membranes, alveolar hemorrhages, petechiae and vasculitis in the central nervous system, interstitial myocarditis, multifocal interstitial nephritis and hemorrhages, splenomegaly, portal triaditis, and mucosal hemorrhages in urinary tract. Immunofluorescent R. typhi were demonstrated in the lungs, brain, kidneys, liver, and heart. This unusual death occurred in an elderly patient without rash who was treated too late with antirickettsial drugs.
Assuntos
Rickettsia typhi/isolamento & purificação , Tifo Endêmico Transmitido por Pulgas/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/análise , Feminino , Imunofluorescência , Humanos , Nefrite/diagnóstico , Nefrite/patologia , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/patologia , Tifo Endêmico Transmitido por Pulgas/patologia , Infecções Urinárias/diagnóstico , Infecções Urinárias/patologia , Vasculite/diagnóstico , Vasculite/patologiaRESUMO
OBJECTIVE: To document the clinical, laboratory, and epidemiologic characteristics of pediatric patients with murine typhus. DESIGN: Pediatric patients were diagnosed using serologic testing, and clinical, laboratory, and epidemiologic data were retrospectively reviewed. SETTING: Of 97 patients, 77 (79%) were identified and treated as inpatients and 20 (21%) were treated as outpatients; most resided in south Texas. PATIENTS: Between 1979 and 1996, medical records and patient-physician interviews were available for 97 patients aged 16 years and younger with murine typhus. MAIN OUTCOME MEASURES: The frequency of clinical symptoms and signs, abnormal laboratory findings, epidemiologic findings, and measures of disease severity were determined. RESULTS: The clinical triad of fever, headache, and rash occurred in only 43 (49%) of 87 pediatric patients throughout the illness. Musculoskeletal symptoms were experienced by 43% of patients, whereas gastrointestinal tract symptoms (nausea, vomiting, anorexia, and diarrhea) occurred in 77%. Systemic involvement was evident by the frequent occurrence of abnormal laboratory findings referable to multiple organ systems, including the liver, kidney, blood, and central nervous system. CONCLUSIONS: Pediatric infection by Rickettsia typhi usually causes mild to moderate systemic illness. In children, the median duration of illness was 12 days (range, 5-29 days), but severe complications were rare. Length of illness was significantly related to the initial diagnosis, whereas the interval to defervescence was related to therapy with a tetracycline or chloramphenicol. Early recognition and treatment is important to prevent prolonged morbidity.