RESUMO
AIM: The aim of the study was to examine whether a combination of self-reported masticatory ability and regular dental care is linked to mortality and issuance of new long-term care insurance (LTCI) service certifications. METHODS: Older residents in institutions or in need of LTCI certification requirements were excluded, and self-administered questionnaires were sent to 5,400 older adults in 2013; these participants were followed for 5 years. The total response rate was 94.3%, and our final sample comprised 4,824 older adults (89.3%). We used 3 items to assess self-reported masticatory ability and regular dental care. These included (1) decline in chewing abilities of the posterior teeth on either side, (2) not brushing one's own teeth or dentures at least once a day, and (3) not visiting the dentist at least once a year. RESULTS: The mean age of the participants at baseline was 75.9 years, and 58.4% of them were women. Main outcomes included mortality (n = 562) or new LTCI certification requirements (n = 1187) during the 5-year period. Multivariate analyses revealed that a poor score on masticatory ability and on regular dental care produced significant adverse health outcomes leading to earlier negative outcomes. The score is considered poor as it increases relative to the 0-point reference. DISCUSSION: Regular dental care (both self-and professional care) and maintaining masticatory ability are both important. Hence, public activities focusing on preventive oral health from middle age onward is important.
Assuntos
Assistência Odontológica/métodos , Mastigação/fisiologia , Saúde Bucal/estatística & dados numéricos , Idoso , Feminino , Humanos , Masculino , Mortalidade , Autorrelato , Inquéritos e QuestionáriosRESUMO
Extranodal extension (ENE) of lymph node metastasis and the presence of a positive or close margin (PCM) are major risk factors for head and neck squamous cell carcinoma recurrence. This retrospective multicentre cohort study compared the prognostic impact of postoperative radiotherapy (RT) and concurrent chemoradiotherapy (CCRT) in oral squamous cell carcinoma (OSCC) patients at high risk of recurrence. One hundred and eighteen patients with PCM and/or ENE who underwent definitive surgery plus either adjuvant RT or CCRT using cisplatin for OSCC were investigated. The cohort-wide 5-year loco-regional control (LRC), disease-free survival (DFS), and overall survival (OS) rates (the main outcome measures) were 54.3%, 35.8%, and 43.2%, respectively. Multivariate analysis showed that age ≥64 years (hazard ratio (HR) 0.584), cT3-4 stage (HR 1.927), ≥4 metastatic lymph nodes (HR 1.912), and PCM (HR 2.014) were significant independent predictors of OS. Moreover, postoperative CCRT with cisplatin was associated with a significantly improved LRC rate, but not with improved DFS or OS rates, compared to postoperative RT (HR 0.360). Given that CCRT with cisplatin does not significantly improve survival, additional clinical trials will be required to validate new regimens that further improve the outcomes of patients with loco-regionally advanced OSCC going forward.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Quimiorradioterapia , Estudos de Coortes , Intervalo Livre de Doença , Humanos , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Radioterapia Adjuvante , Estudos RetrospectivosRESUMO
OBJECTIVES: The present study examined whether the combination of self-reported mobility decline (SR-MD) and cognitive decline (SR-CD) was associated with mortality and new long-term care insurance (LTCI) service certifications based on sex and age. DESIGN: A prospective cohort study. SETTING AND PARTICIPANTS: We analyzed cohort data from a sample of older adult residents in Kami Town, Japan. The response rate was 94.3%, and we followed 5,094 older adults for 3 years. Full analyses were conducted on 5,076 participants. MEASURES: A total of four groups were determined through self-reported responses on the Kihon Checklist for SR-MD (a score of 3 or more on 5 items) and SR-CD (a score of 1 or more on 3 items): non-SR-cognitive frailty, non-SR-MD and SR-CD, SR-MD and non-SR-CD, and SR-cognitive frailty. RESULTS: Main outcomes included mortality (n = 262) or new certifications for LTCI services (n = 708) during the 3-year period. Excluding overlapping, this included 845 older adults (16.6%). Among men, prevalence of non-SR-cognitive frailty, non-SR-MD and SR-CD, SR-MD and non-SR-CD, and SR-cognitive frailty (SR-MD and SR-CD) was 48.2%, 26.4%, 11.5%, and 13.8%, respectively. Respective rates for women were 45.7%, 15.5%, 23.1%, and 15.7%. Multivariate analyses revealed that for men, SR-MD and non-SR-CD significantly affected adverse health outcomes, leading to earlier negative outcomes relative to the non-SR-MD and SR-CD group. For women, non-SR-MD and SR-CD and SR-MD and non-SR-CD had similar slopes. CONCLUSIONS: The impact of SR-MD or SR-CD on adverse health outcomes differed as a function of age and sex. Thus, we need to consider preventive approaches according to these specific target group features.
Assuntos
Cognição/fisiologia , Idoso Fragilizado/estatística & dados numéricos , Fragilidade/mortalidade , Limitação da Mobilidade , Autorrelato/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Lista de Checagem , Estudos de Coortes , Feminino , Fragilidade/diagnóstico , Humanos , Vida Independente , Seguro de Assistência de Longo Prazo , Japão/epidemiologia , Masculino , Prevalência , Estudos ProspectivosRESUMO
The aim of this phase II, multicentre, randomized controlled trial was to evaluate the effectiveness of a comprehensive oral management protocol for the prevention of severe oral mucositis in patients with oral cancer receiving radiotherapy alone or chemoradiotherapy. In total, 124 patients with oral cancer were enrolled from five institutions. Of these, 37 patients undergoing radiotherapy were randomly divided into an intervention group (n=18) and a control group (n=19). The remaining 87 patients, who were undergoing chemoradiotherapy, were also randomized into an intervention group (n=42) and a control group (n=45). During radiotherapy, patients in the control group received only oral care, while those in the intervention group additionally received spacers to cover the entire dentition, pilocarpine hydrochloride, and topical dexamethasone ointment for oral mucositis. The primary endpoint was the incidence of severe oral mucositis. The intervention was significantly associated with a decreased incidence of severe oral mucositis in patients receiving radiotherapy alone (P=0.046), but not in those receiving chemoradiotherapy (P=0.815). These findings suggest that an oral management protocol can prevent severe oral mucositis in patients with oral cancer undergoing radiotherapy without concurrent chemotherapy.
Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Estomatite , Administração Oral , Quimiorradioterapia , HumanosRESUMO
WHAT IS KNOWN AND OBJECTIVE: Patients' poor adherence to medications is reported to be related to the individual patients' beliefs and cognitions and their trust of the medical staff. However, the causes of the two forms of non-adherence, intentional and unintentional behaviours, have yet to be clarified. This study compared psychological latent factors associated with intentional and unintentional non-adherence to chronic medication regimens, focusing on the potential effects of (i) patients' dissatisfaction with treatment and their relationships with the medical staff and (ii) patients' subliminal rational thinking processes, which weighed the positive values such as their expectations of benefits from treatment against negative values such as their dissatisfaction. METHODS: Two cross-sectional surveys were undertaken of patients given medications for chronic diseases, using a questionnaire developed and validated in this study. One survey was undertaken in three hospitals and the other survey, online throughout Japan. We scored the individual latent factors using the questionnaire and calculated the differential score between two negatively correlated latent factors to quantify patients' subliminal rational thinking process. We compared the adjusted odds ratio (OR) of latent factors between intentional and unintentional non-adherence to medication in both surveys. RESULTS AND DISCUSSION: Of the eligible subjects, 149 hospitalized patients and 524 survey participants completed the questionnaire. Intentional non-adherence was associated with patient dissatisfaction with treatment including interpersonal relationships with medical staff in both hospitalized patients and online survey participants (95% confidence interval of adjusted OR for Dissatisfaction, 1·20-16·26 in the hospital-based survey and 1·33-3·45 in the online survey). In both surveys, intentional non-adherence was significantly associated with the differential score between two negatively correlated latent factors, Willingness and Dissatisfaction (P = 0·02 in the hospital-based survey and P < 0·001 in the online survey). However, these associations were not evident in unintentionally non-adherent patients. WHAT IS NEW AND CONCLUSIONS: Patients' dissatisfaction and their resulting rational judgments are unique, consistent determinants of intentional non-adherence to medications, but not of unintentional non-adherence.
Assuntos
Julgamento , Adesão à Medicação , Satisfação do Paciente , Adulto , Idoso , Doença Crônica/tratamento farmacológico , Estudos Transversais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Relações Profissional-Paciente , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Muscle volume in patients with muscle disease is an index of disease progression. The aim of this study was to demonstrate a new method of muscle volumetry using CT of thigh muscles. DESIGN: Observational study. PARTICIPANTS: (1) For muscle volumetry using CT and dual-energy X-ray absorptiometry (DXA), 13 patients with muscle disease participated. (2) For prospective CT volumetry, 12 patients participated over 4 years. PRIMARY AND SECONDARY OUTCOME MEASURES: To establish the new CT volumetry, the results of which were correlated with the muscle mass calculated from DXA (primary outcome). To show the decrease in muscle volume using our method over 4 years (secondary outcome) METHODS: (1) Helical CT imaging of the thigh was performed. CT images were analysed by applying estimated functions, and the accumulation of outcomes resulted in muscle volumes. We refer to this method as 'net muscle volumetry'. Simultaneously, DXA was performed in these patients, and the muscle mass of the thigh was calculated with vendor-provided software. (2) To evaluate longitudinal changes in muscle volume, net muscle volumetry at the 14 cm section of the middle part of the thigh was performed repeatedly over a 4-year period. RESULTS: (1) Volumes of the thigh muscle on one side were calculated to be 300-3400 cm(3) using CT. Muscle mass of the thigh was calculated from DXA to be 1100-5000 g. These results correspond closely, with a Pearson correlation coefficient of 0.993. (2) Thigh net muscle volumes of seven patients with gait disturbance decreased over the 4-year study period (p<0.01). CONCLUSIONS: A method of measuring net muscle volume using CT, which was validated by muscle mass calculated from DXA, was developed. Decrements in net muscle volume over 4 years support the reliability of this method. This less arbitrary method is suitable for assessment of muscle volume in patients with muscular dystrophy.
RESUMO
BACKGROUND AND PURPOSE: The presence of cervical lymph node metastases is an important prognostic factor for oral tongue cancer. The accurate preoperative assessment is essential for treatment. Several studies have suggested that histologic tumor thickness is related to the metastases. The aim of this study was to determine whether MR images of oral tongue tumor have the potential to predict cervical lymph node metastases. MATERIALS AND METHODS: A total of 43 patients with squamous cell carcinoma of the oral tongue were investigated. Tumor thickness, sublingual distance between tumor and sublingual space, and paralingual distance between tumor and paralingual space, as determined from coronal MR imaging, were preoperatively estimated. Logistic regression analysis was used to identify independent predictors of lymph node metastases. RESULTS: Univariate logistic regression analysis showed that T classification, N classification, and 3 measured MR imaging distances (millimeters) were significantly associated with lymph node metastases. Multivariate logistic regression analysis showed that tumor thickness (odds ratio, 1.34; 95% confidence interval [CI], 1.11-1.63; P < .005) and paralingual distance (odds ratio, 0.53; 95% CI, 0.35-0.82; P < .005) were significant predictors for lymph node metastases. The probability of metastases was estimated with these models. The preoperative decision (20% probability) as to whether to perform neck dissection could be based on tumor thickness of >9.7 mm and paralingual distance of <5.2 mm. CONCLUSION: MR images provide satisfactory accuracy for the preoperative estimation of the tumor thickness and the paralingual distance, which are valuable for predicting cervical lymph node metastases.
Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Linfonodos/patologia , Imageamento por Ressonância Magnética/métodos , Neoplasias da Língua/patologia , Língua/patologia , Idoso , Idoso de 80 Anos ou mais , Vértebras Cervicais , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias da Língua/secundárioRESUMO
A 56-year-old man had undergone ascending aorta and total arch replacement because of aortic dissection (Stanford type A) in 1997. He had onset of diplegia of the lower limb and vesicorectal disability. Computed tomography (CT) showed serpentine aneurysm in the descending aorta, it was seen between the left subclavian artery and diaphragm level. It was 80 mm of maximum diameter. Magnetic resonance imaging (MRI) was performed for identified Adamkiewicz artery, but we could not identify it. We performed a graft replacement. The 8th intercostal artery was reconstructed with a branch graft. The postoperative course was uneventful. We conclude that graft replacement for spinal ischemia can be effective.
Assuntos
Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular , Paralisia/etiologia , Isquemia do Cordão Espinal/etiologia , Aorta Torácica/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-OperatóriasRESUMO
We report 2 cases of nasolabial cyst and a case of schwannoma beneath the alar base that required a differential diagnosis because of clinical features and MR images that resembled the nasolabial cyst. The morphologic analysis on MR images revealed the characteristic appearance of the nasolabial cyst, and the sagittal MR image may be most helpful for diagnosing this rare disease.
Assuntos
Cistos/diagnóstico , Neoplasias Labiais/diagnóstico , Neurilemoma/diagnóstico , Neoplasias Nasais/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Adolescente , Tecido Conjuntivo/patologia , Cistos/patologia , Feminino , Humanos , Lábio/patologia , Neoplasias Labiais/patologia , Masculino , Pessoa de Meia-Idade , Neurilemoma/patologia , Nariz/patologia , Neoplasias Nasais/patologia , Neoplasias de Tecidos Moles/patologiaRESUMO
A 53-year-old man presented with cough, sputa and chest pain. The chest X-ray revealed a large mass shadow in the right lower lobe. Massive tumor extending into the left atrium was diagnosed by computed tomography (CT). The brushing cytology by broncoscopy was squamous cell carcinoma and its stage was IIIB. Chemothrapy using cisplatin, paclitaxel and gemcitabine hydrochloride was performed 8 courses during 6 months. The effect of the chemotherapy was complete response, enabling the surgical treatment. The right pneumonectomy with partial resection of the left atrium was performed by using vascular clamp. The defect of the left atrium could be sutured directly. Wide-spread necrotic change with very small amount of cancer cells in the atrial wall was confirmed by pathology. The patient has been well for 3 years and 6 months after surgery.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/patologia , Neoplasias Cardíacas/patologia , Neoplasias Pulmonares/patologia , Pneumonectomia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/cirurgia , Procedimentos Cirúrgicos Cardíacos , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Esquema de Medicação , Átrios do Coração , Neoplasias Cardíacas/cirurgia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Paclitaxel/administração & dosagem , GencitabinaRESUMO
Ameloblastoma is one of the well-known odontogenic tumours that can be associated with calcifying odontogenic cysts (COCs), but only a few reports include detailed clinical and radiographic features. In this paper we demonstrate a case of large ameloblastomatous COC in the mandible. The radiographic examination revealed the presence of a multilocular cystic lesion in the right posterior part of the mandible containing the impacted lower second molar with remarkable expansion toward both lingual and buccal side. This feature was different from the general findings of COC and rather resembled that of ameloblastomas.
Assuntos
Ameloblastoma/diagnóstico por imagem , Neoplasias Mandibulares/diagnóstico por imagem , Cisto Odontogênico Calcificante/diagnóstico por imagem , Adolescente , Ameloblastoma/complicações , Ameloblastoma/patologia , Humanos , Masculino , Neoplasias Mandibulares/complicações , Neoplasias Mandibulares/patologia , Cisto Odontogênico Calcificante/complicações , Cisto Odontogênico Calcificante/patologia , Radiografia , Dente Impactado/complicações , Dente Impactado/diagnóstico por imagemRESUMO
A case of advanced gingival cancer is described. The cancer invaded into the mandible and skin of the cheek and was associated with cervical lymph node metastases, mediastinal lymph node metastases, and bilateral multiple pulmonary metastases. The patient received neoadjuvant chemoradiotherapy and local immunotherapy, followed by curative surgery for the primary and neck lesions. Histopathological examination of the primary cancer and the upper and middle cervical nodes (n = 7) indicated a diagnosis of squamous cell carcinoma. Sections of the lower cervical nodes (n = 5) revealed well-differentiated thyroid carcinoma, suggesting that the mediastinal and pulmonary lesions were of thyroid origin. After total thyroidectomy and mediastinal dissection followed by treatment with radioiodine, the multiple pulmonary nodules disappeared. There has been no evidence of recurrent tumour for 5 years.
Assuntos
Carcinoma Papilar/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Gengivais/patologia , Neoplasias Pulmonares/secundário , Neoplasias Primárias Múltiplas/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Carcinoma Papilar/secundário , Carcinoma de Células Escamosas/secundário , Feminino , Humanos , Metástase Linfática/patologia , Neoplasias Primárias Múltiplas/secundárioRESUMO
For 1 week, healthy human participants ( n=7) were devoid of normal vision by exposure to prism lenses that optically rotated their perceived world around the line of sight by 180 degrees. Adaptation to such prisms involved sustained and vigorous practice of the ability to redirect the unadapted efferent motor command; because prior to all visually guided movements, the to-be-executed efferent command was based on incorrect (prismatically reversed) spatial information. The time course of this sort of adaptation was systematically explored in Cooper-Shepard mental rotation (MR) tests and in naturalistic motor-tasks for the purpose of investigating whether mental rotations of the direction of the intended movement share common aspects with the process of MR. A control group ( n=7) intermittently exposed to the distorted spatial organization of the central visual field was studied in parallel. The main results were as follows: (a) the MR reaction times (RTs) day 1 with prisms appeared to be very similar to the normal RTs (day 1, no-prisms) with the one exception that subjects now responded within a prism (rotated) frame of spatial reference rather than within the environmentally upright. The visuomotor performance became grossly irregular and dysmetric. (b) The majority of the visuomotor adaptation functions began to level off on the 3rd day. (c) The increases in natural motor proficiency were accompanied by a systematic and noticeable decrease in magnitude of the MR Y-intercept obtained from the linear regression line calculated between each subject's RT and the various stimulus angles. MR slopes were stable through days 1-7 for both the experimental and control group. An increased correlation between rotational stimulus angle and RT suggested that the MR function also became progressively more tightly coupled to the stimulus angles. (d) Postadaptation measures of performance indicated the occurrence of selective and minimal adaptation in the natural motor tasks only. It is suggested that these results reflect an improved attentional (strategic) ability to replace incorrect (error producing) control signals with correct (error reducing) control signals. As a result, perceptual-motor start-up processes directly related to spatial coding and to the planning, initiation and correction of the intended direction of motor-or-mental movement improved while the subprocess ("stage") concerned with transformations of such movements remained unchanged. Visuomotor adaptation to inverting prisms engages, and thereby stimulates, a cortical system also invoked in the preparatory process of MR.
Assuntos
Adaptação Fisiológica/fisiologia , Ilusões/fisiologia , Lobo Parietal/fisiologia , Desempenho Psicomotor/fisiologia , Percepção Espacial/fisiologia , Córtex Visual/fisiologia , Campos Visuais/fisiologia , Vias Visuais/fisiologia , Adulto , Retroalimentação/fisiologia , Marcha/fisiologia , Humanos , Imaginação/fisiologia , Aprendizagem/fisiologia , Lentes/efeitos adversos , Masculino , Transtornos das Habilidades Motoras/etiologia , Transtornos das Habilidades Motoras/fisiopatologia , Movimento/fisiologia , Plasticidade Neuronal/fisiologia , Testes Neuropsicológicos , Orientação/fisiologia , Estimulação Luminosa , Recuperação de Função Fisiológica/fisiologia , Fatores de TempoRESUMO
Familial and sporadic forms of narcolepsy exist in both humans and canines. Mutations in the hypocretin receptor 2 gene (Hcrtr 2) cause canine familial narcolepsy. In humans, mutations in hypocretin-related genes are rare, but cerebrospinal fluid (CSF) hypocretin-1 is undetectable in most sporadic cases. Using the canine model, we investigated ( 1 ) whether hypocretin deficiency is involved in sporadic cases and ( 2 ) whether alterations in hypocretin neurons or ligand levels also contribute to the phenotype in Hcrtr 2 mutants. We found that hypocretins were undetectable in the brains of three of three and the CSF of two of two sporadic narcoleptic dogs tested. In contrast, hypocretin levels were not altered in brains and CSF of genetically narcoleptic Dobermans, and hypocretin-containing neurons were of normal appearance. Therefore, multiple hypocretin-related etiologies are likely to be involved in canine narcolepsy. The presence of hypocretin peptides in Hcrtr 2-mutated animals suggests that neurotransmission through Hcrtr 1 may be intact, arguing for a preferential importance of Hcrtr 2-mediated function in narcolepsy.
Assuntos
Proteínas de Transporte/líquido cefalorraquidiano , Peptídeos e Proteínas de Sinalização Intracelular , Narcolepsia/líquido cefalorraquidiano , Neuropeptídeos/líquido cefalorraquidiano , Fatores Etários , Animais , Química Encefálica , Proteínas de Transporte/análise , Proteínas de Transporte/sangue , Cães , Imuno-Histoquímica , Mutação , Narcolepsia/sangue , Narcolepsia/genética , Neurônios/química , Neuropeptídeos/análise , Neuropeptídeos/sangue , Orexinas , RadioimunoensaioRESUMO
Periodic leg movements during sleep (PLMS) is a high prevalent sleep disorder of unknown etiology. The disease is pharmacologically treated with dopaminergic agonists (i.e. D2/D3 agonists) and opiates. Periodic leg movements during sleep often occur in narcoleptic patients. We observed that narcoleptic canines, like narcoleptic humans, also exhibit jerky, unilateral or bilateral slow leg movements during sleep. The movements in dogs are characterized by repetitive dorsiflexions of the ankle, lasting 0.5-1.5 s, and occur at regular intervals of 3-20 s, thus showing similarities to PLMS in humans. The observation that D2/D3 agonists aggravate cataplexy in narcoleptic dogs suggests that altered dopaminergic regulation in canine narcolepsy may play a critical role in both cataplexy and PLMS. Our canines may therefore be an invaluable resource in PLMS research.
Assuntos
Narcolepsia/complicações , Síndrome da Mioclonia Noturna/complicações , Animais , Cães , Agonistas de Dopamina/efeitos adversos , Eletrodos Implantados , Eletroencefalografia , Eletromiografia , Eletroculografia , Masculino , Narcolepsia/induzido quimicamente , Narcolepsia/genética , Síndrome da Mioclonia Noturna/tratamento farmacológico , Receptores de Orexina , Mutação Puntual/genética , Polissonografia , Receptores Acoplados a Proteínas G , Receptores de Neuropeptídeos/genética , Sono REM/efeitos dos fármacosRESUMO
Intracellular Ca(2+) in Trypanosoma cruzi is mainly located in an acidic compartment named the acidocalcisome, which among other pumps and exchangers possesses a plasma membrane-type Ca(2+)-ATPase. Evidence for an endoplasmic reticulum-located Ca(2+) uptake has been more elusive and based on indirect results. Here we report the cloning and sequencing of a gene encoding a sarcoplasmic-endoplasmic reticulum-type Ca(2+)-ATPase from T. cruzi. The protein (TcSCA) predicted from the nucleotide sequence of the gene has 1006 amino acids and a molecular mass of 109.7 kDa. Several sequence motifs found in sarcoplasmic-endoplasmic reticulum-type Ca(2+)-ATPases were present in TcSCA. Expression of TcSCA in yeast mutants deficient in the Golgi and vacuolar Ca(2+) pumps (pmr1 pmc1 cnb 1) restored growth on EGTA. Membranes were isolated from the pmr1 pmc1 cnb1 mutant transformed with TcSCA, and it was found that the TcSCA polypeptide formed a Ca(2+)-dependent and hydroxylamine-sensitive (32)P-labeled phosphoprotein of 110 kDa in the presence of [gamma-(32)P]ATP. Cyclopiazonic acid, but not thapsigargin, blocked this phosphoprotein formation. Transgenic parasites expressing constructs of TcSCA with green fluorescent protein exhibited co-localization of TcSCA with the endoplasmic reticulum proteins BiP and calreticulin. An endoplasmic reticulum location was also found in amastigotes and trypomastigotes using a polyclonal antibody against a COOH-terminal region of the protein. The ability of TcSCA to restore growth of mutant pmr1 pmc1 cnb 1 on medium containing Mn(2+) suggests that TcSCA may also regulate Mn(2+) homeostasis by pumping Mn(2+) into the endoplasmic reticulum of T. cruzi.
Assuntos
ATPases Transportadoras de Cálcio/genética , ATPases Transportadoras de Cálcio/metabolismo , Retículo Endoplasmático/enzimologia , Transcrição Gênica , Trypanosoma cruzi/enzimologia , Trypanosoma cruzi/genética , Sequência de Aminoácidos , Animais , Cálcio/metabolismo , ATPases Transportadoras de Cálcio/química , Clonagem Molecular , Teste de Complementação Genética , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático , Alinhamento de Sequência , Homologia de Sequência de AminoácidosRESUMO
Cataplexy, an abnormal manifestation of REM sleep atonia, is currently treated with antidepressants. These medications also reduce physiological REM sleep and induce nocturnal sleep disturbances. Because a recent work on canine narcolepsy suggests that the mechanisms for triggering cataplexy are different from those for REM sleep, we hypothesized that compounds which act specifically on cataplexy, but not on REM sleep, could be developed. Canine studies also suggest that the dopamine D2/D3 receptor mechanism is specifically involved in the regulation of cataplexy, but little evidence suggests that this mechanism is important for REM sleep regulation. We therefore assessed the effects of sulpiride, a commonly used D2/D3 antagonist, on cataplexy and sleep in narcoleptic canines to explore the possible clinical application of D2/D3 antagonists for the treatment of human narcolepsy. Both acute and chronic oral administration of sulpiride (300 mg/dog, 600 mg/dog) significantly reduced cataplexy without noticeable side effects. Interestingly, the anticataplectic dose of sulpiride did not significantly reduce the amount of REM sleep. Sulpiride (and other D2/D3 antagonists) may therefore be an attractive new therapeutic indication in human narcolepsy.
Assuntos
Cataplexia/tratamento farmacológico , Cataplexia/psicologia , Antagonistas de Dopamina/uso terapêutico , Antagonistas dos Receptores de Dopamina D2 , Narcolepsia/tratamento farmacológico , Narcolepsia/psicologia , Sono REM/efeitos dos fármacos , Sulpirida/uso terapêutico , Animais , Nível de Alerta/efeitos dos fármacos , Cães , Eletroencefalografia , Feminino , Masculino , Narcolepsia/genética , Receptores de Dopamina D3RESUMO
OBJECTIVE: To determine the mode of inheritance of von Willebrand's disease (vWD) and perform linkage analysis between vWD and coat color or narcolepsy in a colony of Doberman Pinschers. ANIMALS: 159 Doberman Pinschers. PROCEDURE: von Willebrand factor antigen (vWF:Ag) concentration was measured by use of ELISA, and results were used to classify dogs as having low (< 20%), intermediate (20 to 65%), or high (> 65%) vWF:Ag concentration, compared with results of analysis of standard pooled plasma. Buccal bleeding time was measured, and mode of inheritance of vWD was assessed by pedigree analysis. RESULTS: von Willebrand's disease was transmitted as a single autosomal gene defect. Results suggested that 27.04% of dogs were homozygous for vWD, 62.26% were heterozygous, and 10.69% did not have the defect. Most homozygous and some heterozygous dogs had prolonged bleeding times. Dogs with diluted coat colors (blue and fawn) were significantly overrepresented in the homozygous group, compared with black and red dogs, but a significant link between vWD and coat color was not detected. CONCLUSIONS AND CLINICAL RELEVANCE: von Willebrand's disease is transmitted as an autosomal dominant trait with variable penetrance; most dogs in this colony (89.3%) were carriers of vWD. Homozygosity for vWD is not likely to be lethal. Some heterozygous dogs have prolonged bleeding times. An association between diluted coat colors and vWD may exist.