RESUMO
BACKGROUND: PLA2G6 is the causative gene for infantile neuroaxonal dystrophy, neurodegeneration associated with brain iron accumulation, and Karak syndrome. Based on previous reports, patients with PLA2G6 mutations could show axonal dystrophy, dystonia, dementia, and cerebellar signs. Recently, PLA2G6 was also reported as the causative gene for early-onset PARK14-linked dystonia-parkinsonism. METHODS: To clarify the role of PLA2G6 mutation in parkinsonism, we conducted mutation analysis in 29 selected patients with very early-onset (≤ 30, mean 21.2 ± 8.4 years, ± SD) parkinsonism. These patients had other clinical features (e.g., mental retardation/dementia [14/29], psychosis [15/29], dystonia [11/29], and hyperreflexia [11/29]). RESULTS: Two novel compound heterozygous PLA2G6 mutations were detected (patient A: p.F72L/p.R635Q; patients B1 and B2: p.Q452X/p.R635Q). All 3 patients had early-onset l-dopa-responsive parkinsonism with dementia and frontotemporal lobar atrophy. Disease progression was relatively rapid. SPECT in patient B1 showed frontotemporal lobar hypoperfusion. MRI in patient A showed iron accumulation in the substantia nigra and striatum. CONCLUSIONS: Although the clinical presentation of PLA2G6-associated neurodegeneration was reported to be homogeneous, our findings suggest patients with PLA2G6 mutation could show heterogeneous phenotype such as dystonia-parkinsonism, dementia, frontotemporal atrophy/hypoperfusion, with or without brain iron accumulation. Based on the clinical heterogeneity, the functional roles of PLA2G6 and the roles of PLA2G6 variants including single heterozygous mutations should be further elucidated in patients with atypical parkinsonism, dementia, or Parkinson disease. PLA2G6 mutations should be considered in patients with early-onset l-dopa-responsive parkinsonism and dementia with frontotemporal lobar atrophy.
Assuntos
Predisposição Genética para Doença , Fosfolipases A2 do Grupo VI/genética , Mutação/genética , Transtornos Parkinsonianos/genética , Fenótipo , Adolescente , Adulto , Idade de Início , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Análise Mutacional de DNA/métodos , Feminino , Demência Frontotemporal/genética , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Transtornos Parkinsonianos/diagnóstico por imagem , Transtornos Parkinsonianos/patologia , Transtornos Parkinsonianos/fisiopatologia , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto JovemRESUMO
BACKGROUND: With the International Classification of Functioning, Disability and Health (ICF), we can now rely on a globally agreed-upon framework and system for classifying the typical spectrum of problems in the functioning of persons given the environmental context in which they live. ICF Core Sets are subgroups of ICF items selected to capture those aspects of functioning that are most likely to be affected by sleep disorders. OBJECTIVE: The objective of this paper is to outline the developmental process for the ICF Core Sets for Sleep. METHODS: The ICF Core Sets for Sleep will be defined at an ICF Core Sets Consensus Conference, which will integrate evidence from preliminary studies, namely (a) a systematic literature review regarding the outcomes used in clinical trials and observational studies, (b) focus groups with people in different regions of the world who have sleep disorders, (c) an expert survey with the involvement of international clinical experts, and (d) a cross-sectional study of people with sleep disorders in different regions of the world. CONCLUSION: The ICF Core Sets for Sleep are being designed with the goal of providing useful standards for research, clinical practice and teaching. It is hypothesized that the ICF Core Sets for Sleep will stimulate research that leads to an improved understanding of functioning, disability, and health in sleep medicine. It is of further hope that such research will lead to interventions and accommodations that improve the restoration and maintenance of functioning and minimize disability among people with sleep disorders throughout the world.
Assuntos
Avaliação da Deficiência , Nível de Saúde , Cooperação Internacional , Transtornos do Sono-Vigília/classificação , Transtornos do Sono-Vigília/prevenção & controle , Humanos , Transtornos do Sono-Vigília/terapia , Organização Mundial da SaúdeAssuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Displasia Ectodérmica/terapia , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Quinase I-kappa B/genética , Síndromes de Imunodeficiência/terapia , Condicionamento Pré-Transplante/métodos , Pré-Escolar , Displasia Ectodérmica/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Síndromes de Imunodeficiência/genética , Masculino , MutaçãoRESUMO
AIMS: To compare clinical data, sleep quality and health-related quality of life (HRQOL) with and without RLS in HD patients. MATERIALS AND METHODS: The international RLS study group diagnosis questionnaire was completed by 228 HD patients. The Pittsburg Sleep Quality Index (PSQI) for the evaluation of sleep quality and the Kidney Disease Quality of Life (KDQOL-SF) for the analysis of HRQOL were also used. RESULTS: 53 (23%) patients were diagnosed as RLS. Age and age at the initiation of HD were significantly younger in the RLS group. Serum calcium concentration (Ca) was significantly higher in the RLS group. Sleep quality evaluated by PSQI was significantly lower in the RLS group. In SF-36 domains of KDQOL-SF, bodily pain, general health perceptions, vitality, role functioning emotional, mental health and mental component score were significantly lower in the RLS group. In kidney targeted scales of KDQOL-SF, symptoms/problems, burden of kidney disease, cognitive function, quality of social interaction, sleep and patient satisfaction were significantly lower in the RLS group. CONCLUSION: High Ca was possibly connected to the pathophysiology of RLS which impaired sleep quality as well as HRQOL including mental health and many kidney disease related scales.
Assuntos
Cálcio/sangue , Falência Renal Crônica/terapia , Hormônio Paratireóideo/sangue , Qualidade de Vida , Diálise Renal/efeitos adversos , Síndrome das Pernas Inquietas , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/psicologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Diálise Renal/psicologia , Síndrome das Pernas Inquietas/sangue , Síndrome das Pernas Inquietas/etiologia , Síndrome das Pernas Inquietas/psicologia , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
Hepatitis C virus (HCV) is an important cause of liver disease throughout the world. However, the natural history and pathogenesis of this infection is still not completely understood. The aim of this study was to characterize the evolution of incident, asymptomatic HCV infection in a community-based population in Japan. The Miyazaki Cohort Study is a prospective study of adult residents in two villages, one of which has a very high prevalence of HCV. Nine hundred and seventy-three people from this village were enrolled in the cohort between 1984 and 1995, with antibodies to HCV (anti-HCV) found in 23%. During subsequent visits to annual health screens, new HCV seroconverters were identified among susceptible individuals, and their sequential samples were tested for anti-HCV, HCV-RNA, and HCV core antigen. Fourteen participants (six males, eight females) acquired anti-HCV during the first 11 years of study follow-up, at an incidence rate of 362 per 100 000 person-years. Detectable HCV-RNA and high anti-HCV titres (> 1:2048) were observed for more than 5 years following seroconversion in 80% (8/10) of seroconverters with sufficient information, indicating the development of persistent infection in these subjects. Three (37.5%) of the eight sero converters with persistent infection had fairly consistent, albeit mild, alanine aminotransferase elevations (30-130 IU/L) during the study. Anti-HCV seroconversions occurred at a very high rate in this community-based population in Japan, in which this infection is endemic. Persistence also developed at a high frequency among the cases of newly acquired infection, although the associated liver enzyme abnormalities were mild.
Assuntos
Hepatite C/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Estudos de Coortes , Serviços de Saúde Comunitária , Feminino , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C/imunologia , Hepatite C/transmissão , Hepatite C/virologia , Anticorpos Anti-Hepatite C/sangue , Antígenos da Hepatite C/sangue , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Vigilância da População , RNA Viral/sangue , Proteínas do Core Viral/sangueRESUMO
We have produced a novel monoclonal antibody (mAb) directed against Wiskott-Aldrich syndrome protein (WASP) by immunizing mice with the recombinant protein. The mAb designated 5A5 is highly specific to WASP and suitable for Western blot analysis and immunoprecipitation. A flow cytometric assay using the 5A5 mAb identifies expression of intracytoplasmic WASP in lymphocytes from normal individuals. Double staining analysis with cell surface CD3, CD19, and CD56, and intracytoplasmic molecules revealed WASP expression in each subpopulation. With regard to WASP expression in patients with Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT), peripheral blood mononuclear cells (PBMCs) from nine patients and Epstein-Barr virus-transformed B-lymphoblastoid cell lines from seven patients examined did not show WASP expression by flow cytometric analysis. These results were confirmed by Western blot analysis. We conclude that WASP expression in lymphocyte subpopulations from patients with WAS and XLT can be more precisely evaluated by flow cytometry as compared with Western blot analysis. This flow cytometry method is important as a supplement to Western blots, but even more important as an alternative and powerful assay that can contribute to research on WASP as well as diagnosis in a clinical setting.
Assuntos
Citometria de Fluxo/métodos , Linfócitos/metabolismo , Proteínas/análise , Trombocitopenia/sangue , Síndrome de Wiskott-Aldrich/sangue , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/isolamento & purificação , Linhagem Celular Transformada , Citoplasma/metabolismo , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Proteínas/imunologia , Proteína da Síndrome de Wiskott-AldrichRESUMO
BACKGROUND AND OBJECTIVE: It has been suggested that there is a major difference in the ratio of AD to vascular dementia (VaD) between Japan and Western countries. To determine the type-specific prevalence of dementia in community-dwelling elderly from the Japanese community of Nakayama, all patients with dementing illness underwent a CT scan. METHODS: A door-to-door three-phase population survey was carried out on all persons aged 65 years and older residing at home on the prevalence day (January 1, 1997). The ascertainment of cases was made between January 1997 and March 1998. The study included a psychiatric interview; physical, neurologic, and neuropsychologic examinations; comprehensive laboratory tests; and cranial CT. A public health nurse also interviewed a person close to each subject. Dementia was defined according to the Diagnostic and Statistical Manual of Mental Disorders, third edition-revised, criteria, AD according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association, and VaD according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition, combined with information from the patient's neurologic history and CT scanning. RESULTS: Of 1438 inhabitants, 1162 (81.0%) completed the protocol. The prevalence of dementia was 4.8%. Of the 60 subjects with dementia, 35% had AD, 47% had VaD, and 17% had dementia resulting from other causes. CONCLUSIONS: The prevalence of dementia was similar to previous reports, but, contrary to results of virtually all studies conducted in developed countries and those recently conducted in Japan, almost half of the cases in the present study appeared to have VaD with neuroradiologic confirmation.
Assuntos
Demência Vascular/epidemiologia , Inquéritos Epidemiológicos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Demência Vascular/diagnóstico , Feminino , Humanos , Japão/epidemiologia , Masculino , Testes Neuropsicológicos/estatística & dados numéricos , Prevalência , Características de Residência/estatística & dados numéricosRESUMO
Twenty-three human T lymphotropic virus type I (HTLV-I) seroconverters were identified among 1120 HTLV-I-seronegative adults followed up for 11 years in an area of Japan endemic for HTLV-I. The geometric mean titer of anti-HTLV-I was 1:453 in the first year after seroconversion; the titer of each subject did not change significantly during 2-10 years of follow-up. HTLV-I proviral DNA load was quantified in 15 seroconverters, and a broad range of levels was observed-from <10 to >1000 copies/10(5) peripheral blood mononuclear cells. However, there was no obvious change in HTLV-I proviral DNA load over several years within individual subjects. Therefore, both proviral DNA load and humoral response in adult HTLV-I seroconverters were shown to stabilize within a few years after initial infection. In addition, 1 subject tested positive for HTLV-I proviral DNA before antibody seroconversion, which suggests the existence of a window period in community-acquired infection.
Assuntos
Anticorpos Antivirais/sangue , Infecções por HTLV-I/imunologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Provírus/imunologia , Idoso , Estudos de Coortes , Serviços de Saúde Comunitária , DNA Viral/análise , Feminino , Infecções por HTLV-I/sangue , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Japão , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Provírus/genética , Provírus/isolamento & purificação , População Rural , Carga ViralRESUMO
BACKGROUND: Tonic inhibition index (TII) and phasic inhibition index (PII) were proposed as indices for evaluating the degree of two types of motor inhibition activity during rapid eye movement (REM) sleep. METHODS: In the present study, therefore, six healthy men underwent two consecutive all-night polysomnography, and reproducibility of TII and PII was evaluated. RESULTS: TII was 0.85+/-0.07 (mean+/-SD) on the first night and 0.88+/-0.08 on the second; and PII was 3.4+/-2.1 on the first night and 4.9+/-1.8 on the second. Neither TII nor PII was significantly different between the two nights. CONCLUSION: One night sleep study is considered sufficient for using TII and PII as a tool for evaluating motor inhibition activity during REM sleep in adults.
RESUMO
The characteristics and prevalence of hepatitis C virus (HCV)-associated glomerulopathy remain to be determined. To analyze the relationship between HCV infection and glomerulopathy, we enrolled three groups of individuals or patients. The first group consisted of 7776 individuals who were seen for routine checkups. The second group consisted of 86 patients with chronic hepatitis C, 40 patients with chronic hepatitis B, and 51 patients with non-viral liver diseases. The third group consisted of nine patients with HCV association glomerulopathy who underwent renal biopsy. Of the 7776 individuals undergoing medical checkups, 142 (1.8%) were positive for HCV antibody. The positive rate of proteinuria was significantly higher (P<0.030) in individuals with HCV antibody (2.1%) than in those without the antibody (0.6%). Abnormal levels of serum creatinine (5.8 vs. 0%, P=0.025) and complications of cryoglobulinemia (45 vs. 5%, P<0.001) were significantly more common in the 86 patients with chronic hepatitis C (5.8%) than in the 91 patients with other liver diseases. All patients with abnormal levels of serum creatinine had concomitant cryoglobulinemia. Of the nine patients with histologically proven HCV-associated glomerulopathy, four had cryoglobulinemia (all were type II). Elevations of serum creatinine level (4/4 vs. 0/5, P=0.048) and a glomerular legion of membranoproliferative glomerulonephritis (3/4 vs. 0/5, P=0.048), a severe type of glomerulonephritis, were more common in the four patients with cryoglobulinemia than in the remaining five patients. In conclusion, HCV infection was found to be significantly associated with glomerulopathy. In addition, the presence of cryoglobulinemia, which usually accompanies membranoproliferative glomerulonephritis, was found to be an indicator of renal insufficiency in patients with HCV-associated glomerulopathy.
Assuntos
Hepacivirus , Hepatite C/transmissão , Doenças Virais Sexualmente Transmissíveis/transmissão , Adulto , Idoso , Feminino , Hepacivirus/genética , Hepatite C/epidemiologia , Hepatite C/virologia , Humanos , Japão/epidemiologia , Masculino , Casamento , Pessoa de Meia-Idade , RNA Viral/genética , Parceiros Sexuais , Doenças Virais Sexualmente Transmissíveis/epidemiologiaRESUMO
K-ras mutations at codon 12 have been detected in almost all pancreatic adenocarcinomas by highly sensitive assays. We reassessed the K-ras mutation status by direct polymerase chain reaction (PCR) and sequencing from tissue microdissection without DNA extraction in 10 pancreatic adenocarcinomas, and also assessed the K-ras and DPC4 genes in nine pancreatic cancer cell lines. Eight pancreatic adenocarcinomas were found to harbor K-ras mutations at codon 12 of either GTT or GAT, five of which were inferred to harbor amplified mutant alleles. Mutations at the sites other than codon 12 were found in seven of 70 clones (seven of 9,380 bases) by the TA cloning analysis, suggesting that artifactual mutations at the first or second base of codon 12 before and during PCR could occur at a frequency of approximately 10(-3), enough for highly sensitive assays to detect. Two cell lines without K-ras mutations at codon 12 were found to have homozygous deletions at the DPC4 gene. Thus the K-ras mutation status was demonstrated to be correctly determined by just direct sequencing from tissue microdissection. All possible mutations or multiple mutations at K-ras codon 12 that have been reported in pancreatic adenocarcinomas might include artifacts or mutations without a selective advantage. In addition, we must be very cautious about contamination.
Assuntos
Adenocarcinoma/genética , Genes ras/genética , Mutação , Neoplasias Pancreáticas/genética , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Códon , Proteínas de Ligação a DNA/genética , Humanos , Proteína Smad4 , Transativadores/genéticaAssuntos
Sistema ABO de Grupos Sanguíneos , Antifúngicos/uso terapêutico , Incompatibilidade de Grupos Sanguíneos , Imunossupressores/uso terapêutico , Itraconazol/uso terapêutico , Transplante de Rim , Doadores Vivos , Tacrolimo/uso terapêutico , Adulto , Interações Medicamentosas , Humanos , MasculinoRESUMO
Daytime sleepiness is such a familiar thing for most Japanese, dozing off in a commuting train is regarded as completely normal. Sleepiness, however, can yield a lot of problems. Not only deteriorating efficiency of the work, it sometimes leads to traffic accidents, and also serves as a cause for disastrous accidents. Although excessive daytime sleepiness has been gradually known to Japanese health workers as one of the symptoms of sleep apnea syndrome, some patients cannot recognize sleepiness, and even neglect it, feeling others are sleepy as well. In this respect multiple sleep latency test is a valuable tool as an objective measures of daytime sleepiness, and commonly used procedures of this testing was described in details.
Assuntos
Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Polissonografia/métodos , Ritmo Circadiano/fisiologia , Humanos , Narcolepsia/diagnóstico , Tempo de Reação/fisiologia , Síndromes da Apneia do Sono/diagnósticoRESUMO
The main medical treatment of moderate to severe obstructive sleep apnea/hypopnea syndrome is nasal continuous positive airway pressure(nCPAP). When compliance of the patient is low due to nasal or oral dryness, heated humidifier is added to nCPAP. In Japan frequent complaints such as nasal cold and dryness were observed in winter because of infrequent air conditioning in the sleeping room. In the case of dyspnea using nCPAP, bilevel PAP or auto CPAP is recommended. We treated 384 patients with nCPAP and 24% of the patients were added heated humidifier. Auto CPAP and bilevel PAP was administered in 10% and 6% of the patients indicated for PAP treatment, respectively.
Assuntos
Respiração com Pressão Positiva/métodos , Síndromes da Apneia do Sono/terapia , Humanos , Umidade , Cooperação do Paciente , Respiração com Pressão Positiva/instrumentaçãoRESUMO
Computed tomography (CT) scans of lower leg muscles reveal a selective pattern of fat infiltration in the posterior compartment with spared gracilis, semitendinosus, and the lateral head of the gastrocnemius in both McLeod syndrome and chorea-acanthocytosis, which are disorders characterized by the presence of circulating acanthocytes. The selectivity of affected muscles indicates that late onset and slowly progressive muscular atrophy in both diseases could be a consequence of primary myopathy. Asymmetrical muscle involvement may be seen during the process of degeneration only in McLeod syndrome, however, and may be helpful in distinguishing this disease from chorea-acanthocytosis.
Assuntos
Coreia/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Adulto , Coreia/sangue , Coreia/genética , Creatina Quinase/sangue , Éxons/genética , Humanos , Sistema do Grupo Sanguíneo de Kell , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/enzimologia , Tomografia Computadorizada por Raios XRESUMO
A matrix-assisted laser desorption ionization/time-of-flight (MALDI/TOF) mass spectrometry (MS) system was used to detect variant transthyretin (TTR) in immunoprecipitated serum TTR molecules obtained from 6 patients with familial amyloid polyneuropathy (FAP) who were already proven not to have ATTR Val30Met. This simple and quick method showed six different patterns of mass spectra of TTR-related immunoprecipitates from these patients, and in each patient the clearly identified characteristic doublet-shaped ion peaks consisted of normal and variant TTR apart from each other peak with a mass difference between them. DNA sequencing confirmed that the patterns of variant TTR corresponded respectively to ATTR Val30Leu, ATTR Phe33Val, ATTR Asp38Ala, ATTR Ser50Arg, ATTR Ala97Gly and ATTR Ala97Ser. ATTR Asp38Ala and ATTR Ala97Ser are previously unknown variants of TTR leading to the development of FAP. ATTR Phe33Val was found in a Chinese FAP patient and ATTR Ala97Ser in a Taiwanese. Serum analysis using immunoprecipitation and MALDI/TOF MS system can provide useful information when investigating FAP patients with diverse types of variant TTR.
Assuntos
Neuropatias Amiloides/diagnóstico , Pré-Albumina/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Adulto , Idoso , Neuropatias Amiloides/sangue , Neuropatias Amiloides/genética , DNA/química , DNA/isolamento & purificação , Feminino , Humanos , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase , Pré-Albumina/química , Testes de Precipitina , Análise de SequênciaRESUMO
A 67-year-old female patient with biopsy proven AL systemic amyloidosis developed rapidly progressive dyspnea. Chest roentgenogram and CT scan revealed a large right pleural effusion in addition to nodular lesions with bilateral hilar lymphadenopathy. The patient's serum showed IgG lambda type monoclonal gammopathy and she also had Bence Jones proteinuria. The pleural effusion was an exudate that contained many mononuclear cells and a high concentration of protein. Cardiac function was not seriously disturbed. Except for amyloidosis, no other causes for the severe pleural effusion were found. This patient was treated with chemical pleurodesis using Picibanil and a low dose of prednisolone. Eighteen months after this treatment, her right pleural effusion did not recur. Bronchopulmonary tissues are known to be frequently involved by AL systemic amyloidosis, but a nodular pattern of pulmonary amyloid deposition and a unilateral large pleural effusion are rare clinical manifestations in this disease.
Assuntos
Amiloidose/complicações , Pneumopatias/etiologia , Derrame Pleural/etiologia , Idoso , Amiloide/análise , Amiloidose/diagnóstico por imagem , Feminino , Histocitoquímica , Humanos , Pneumopatias/diagnóstico por imagem , Pneumopatias/patologia , Picibanil/uso terapêutico , Derrame Pleural/tratamento farmacológico , Derrame Pleural/patologia , Prednisolona/uso terapêutico , RadiografiaRESUMO
OBJECTIVES: To study the functional development of neuronal systems that suppress muscle activity, we quantified the chronological change of atonia in rapid-eye-movement sleep (REMS). METHODS: REMS atonia was quantified by the tonic and phasic inhibition indices (TII and PII). TII indicates the shortness of chin muscle activity, whereas PII standardizes the simultaneous occurrence of chin muscle activity and bursts of rapid eye movements. TII and PII were calculated in REMS of 135 polysomnographical recordings obtained in healthy humans from premature babies to a 77-year-old man. RESULTS: TII increased significantly with age, while PII decreased significantly. TII reached an adult level at preadolescence, while PII at early infancy. CONCLUSION: Human nervous systems involved in both tonic and phasic inhibition in REMS raise their activities with age. Since TII and PII reach adult levels at different ages, suppression of muscle activity is hypothesized to be mediated through at least 2 independent systems in humans.