RESUMO
Central core disease (CCD) of muscle is an inherited myopathy which is closely associated with malignant hyperthermia (MH) in humans. CCD has recently been shown to be tightly linked to the ryanodine receptor gene (RYR1) and mutations in this gene are known to be present in MH. Mutation screening of RYR1 has led to the identification of two previously undescribed mutations in different CCD pedigrees. One of these mutations was also detected in an unrelated MH pedigree whose members are asymptomatic of CCD. The data suggest a model to explain how a single mutation may result in two apparently distinct clinical phenotypes.
Assuntos
Canais de Cálcio/genética , Genes , Hipertermia Maligna/genética , Proteínas Musculares/genética , Mutação , Miopatias da Nemalina/genética , Adolescente , Animais , Pré-Escolar , Ligação Genética , Humanos , Mitocôndrias/patologia , Dados de Sequência Molecular , Linhagem , Fenótipo , Reação em Cadeia da Polimerase , Coelhos , Canal de Liberação de Cálcio do Receptor de Rianodina , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Especificidade da Espécie , SuínosRESUMO
In most plants, sucrose is the major transported carbon source. Carbon source availability in the form of sucrose is likely to be a major determinant of cell division, and mechanisms must exist for sensing sugar levels and mediating appropriate control of the cell cycle. We show that sugar availability plays a major role during the G(1) phase by controlling the expression of CycD cyclins in Arabidopsis. CycD2 mRNA levels increase within 30 min of the addition of sucrose; CycD3 is induced after 4 h. This corresponds to induction of CycD2 expression early in G(1) and CycD3 expression in late G(1) near the S-phase boundary. CycD2 and CycD3 induction is independent both of progression to a specific point in the cell cycle and of protein synthesis. Protein kinase activity of CycD2- and CycD3-containing cyclin-dependent kinases is consistent with the observed regulation of their mRNA levels. CycD2 and CycD3 therefore act as direct mediators of the presence of sugar in cell cycle commitment. CycD3, but not CycD2, expression responds to hormones, for which we show that the presence of sugars is required. Finally, protein phosphatases are shown to be involved in regulating CycD2 and CycD3 induction. We propose that control of CycD2 and CycD3 by sucrose forms part of cell cycle control in response to cellular carbohydrate status.
Assuntos
Proteínas de Arabidopsis , Arabidopsis/citologia , Arabidopsis/genética , Metabolismo dos Carboidratos , Ciclo Celular/genética , Ciclinas/genética , Arabidopsis/metabolismo , Carbono/metabolismo , Divisão Celular/genética , Ciclina D3 , Ciclinas/metabolismo , Fase G1/genética , Regulação da Expressão Gênica de Plantas , Fosfoproteínas Fosfatases/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Sementes/metabolismo , Sacarose/metabolismoRESUMO
BACKGROUND: At Harvard Community Health Plan (HCHP), Brookline, Mass, a mixed-model health maintenance organization (HMO), coronary angiography is performed at numerous community and tertiary-level teaching hospitals. OBJECTIVE: To determine the appropriateness of coronary angiography within HCHP according to RAND (1992) criteria and to examine the relationship between the appropriateness rating and (1) the clinical indication for catheterization and (2) the extent of anatomic disease. METHOD: A retrospective, randomized hospital medical record review of 292 patients enrolled in HCHP who underwent coronary angiography in 1992, stratified by four distinct HCHP subgroups. RESULTS: Of the coronary angiographies reviewed, 78% were rated appropriate, 16% uncertain, and only 6% inappropriate across the entire sample. Ratings were comparable in all subdivisions of HCHP despite an incidence rate of catheterization in one of the three HMO divisions that was 60% and 40% higher than in the other two divisions. The lowest appropriateness ratings were for Asymptomatic patients (43%) and those with Chest Pain of Uncertain Origin (35%) (capital letters refer to the RAND clinical indication criteria mentioned above). A rating of necessity was not a better discriminator of anatomic disease than a rating of appropriateness alone: 82% and 84%, respectively, were found to have disease by angiography. CONCLUSION: The low HCHP rate of inappropriateness for coronary angiography is comparable with the RAND 1992 New York State data. This finding, coupled with marked differences in the incidence rate of this procedure among the HCHP divisions, is consistent with either major differences in the sickness of the HMO's sub-populations or, more likely, a lack of specificity of the RAND criteria for coronary angiography.
Assuntos
Angiografia Coronária/normas , Idoso , Feminino , Sistemas Pré-Pagos de Saúde , Humanos , Masculino , Massachusetts , Prontuários Médicos , Pessoa de Meia-Idade , Distribuição Aleatória , Estudos RetrospectivosRESUMO
Short cytoplasmic domains of integrin heterodimers are crucial for transduction of signals generated by adhesion of cells to the extracellular matrix. Here, we describe the use of peptides mimicking the intracellular tails of integrin alpha5beta1 to assay in vitro associations with cytoskeletal proteins. Our results suggest that the focal adhesion protein, paxillin, may interact directly with the intracellular region of the integrin beta1 subunit. Paxillin is known to form stable complexes with several signaling molecules, including focal adhesion kinase. Physical interaction between paxillin and the beta1 cytoplasmic domain suggests a model in which paxillin may function as a key intermediary in integrin-mediated signal transduction.
Assuntos
Citoplasma/metabolismo , Proteínas do Citoesqueleto/metabolismo , Integrinas/metabolismo , Peptídeos/metabolismo , Fosfoproteínas/metabolismo , Sequência de Aminoácidos , Adesão Celular , Moléculas de Adesão Celular/metabolismo , Linhagem Celular , Quinase 1 de Adesão Focal , Proteína-Tirosina Quinases de Adesão Focal , Humanos , Dados de Sequência Molecular , Paxilina , Fosforilação , Ligação Proteica , Proteínas Tirosina Quinases/metabolismo , Tirosina/metabolismoRESUMO
The condition of hyperlexia, often associated with autism, is a rare disorder in which children read words precociously but show little comprehension, markedly poor language, behavioral, and interpersonal skills. The relationship of hyperlexia and dyslexia has never been investigated, although suggestions have been made that the two conditions may be related. In light of current research on familial factors in autism, language disorder, dyslexia, and, recently, hyperlexia, this study investigated family histories of twelve hyperlexic children in regard to language, reading, writing, spelling, and other learning problems, handedness, and presence of allergies. Results suggest a distinct familial tendency to disorders of language, reading, writing, and spelling in male relatives, along with an unusually high instance of nonleft-handedness. Allergy information is inconclusive. Descriptive data are presented, and the relationship of symptomatology in hyperlexia and dyslexia is described and discussed. It is suggested that hyperlexia may represent a point of convergence of several genetically-linked developmental disorders.
RESUMO
To improve, managers need information on the process of care and patient satisfaction. The study described in this article validates a survey for assessing the process of care and satisfaction with ambulatory care visits and illustrates how this information can be used to estimate the impact of different visit processes on patient satisfaction.
Assuntos
Sistemas Pré-Pagos de Saúde/normas , Avaliação de Processos e Resultados em Cuidados de Saúde/organização & administração , Satisfação do Paciente/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Agendamento de Consultas , Coleta de Dados , Feminino , Sistemas Pré-Pagos de Saúde/organização & administração , Acessibilidade aos Serviços de Saúde , Pesquisa sobre Serviços de Saúde/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Organizacionais , New England , Relações Médico-Paciente , Inquéritos e QuestionáriosRESUMO
This two-year longitudinal study of 121 6-12-year-old children in the custody of their mothers following parental separation examined main and interacting effects of child's age and gender, frequency and regularity of visitation, father-child closeness, and parental legal conflict on children's self-esteem and behavioral adjustment at two time points. Predictors were found to have different implications for different groups of children and for children in different situations. Findings suggest the futility of seeking simple answers to whether ongoing contact with fathers following divorce is beneficial or detrimental for children.
Assuntos
Custódia da Criança , Divórcio/psicologia , Relações Pai-Filho , Desenvolvimento da Personalidade , Adaptação Psicológica , Criança , Feminino , Identidade de Gênero , Humanos , Masculino , Meio SocialRESUMO
Molecular genetic linkage studies on the inherited human disorder malignant hyperthermia have resulted in the mapping of the locus for malignant hyperthermia susceptibility (MHS) to the twenty centimorgan genetic interval in the q12-13.2 region of chromosome 19 defined by the anonymous polymorphic DNA markers D19S9 and BCL3. The mapping of the MHS locus to this interval now allows diagnosis of MHS in selected families with an accuracy of 97.5% using closely linked polymorphic DNA markers.
Assuntos
Cromossomos Humanos Par 19/análise , Hipertermia Maligna/genética , Marcadores Genéticos/análise , Genótipo , Humanos , Polimorfismo de Fragmento de RestriçãoAssuntos
Transtornos Cognitivos/diagnóstico , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Transtornos da Linguagem/diagnóstico , Leitura , Percepção Auditiva , Transtorno Autístico/psicologia , Criança , Pré-Escolar , Transtornos Cognitivos/psicologia , Dislexia/genética , Feminino , Humanos , Transtornos do Desenvolvimento da Linguagem/psicologia , Masculino , Rememoração Mental , Destreza Motora , Testes Psicológicos , Comportamento Estereotipado , Aprendizagem Verbal , Percepção VisualAssuntos
Aborto Legal , Aborto Legal/economia , Connecticut , Feminino , Financiamento Governamental , Humanos , Legislação como Assunto , Gravidez , Estados UnidosRESUMO
Natriuretic peptides are linked to osmoregulation, cardiovascular and volume regulation in fishes. The peptides bind to two guanylyl-cyclase-linked receptors, natriuretic peptide receptor-A (NPR-A) and NPR-B, to elicit their effects. Atrial natriuretic peptide (ANP) binds principally to NPR-A, whereas C-type natriuretic peptide (CNP) binds to NPR-B. The teleost kidney has an important role in the maintenance of fluid and electrolyte balance; therefore, the location of NPR-A and NPR-B in the kidney could provide insights into the functions of natriuretic peptides. This study used homologous, affinity purified, polyclonal antibodies to NPR-A and NPR-B to determine their location in the kidney of the Japanese eel, Anguilla japonica. Kidneys from freshwater and seawater acclimated animals were fixed overnight in 4% paraformaldehyde before being paraffin-embedded and immunostained. NPR-A immunoreactivity was found on the apical membrane of proximal tubule 1 and the vascular endothelium including the glomerular capillaries. In contrast, NPR-B immunoreactivity was located on the smooth muscle of blood vessels including the glomerular afferent and efferent arterioles, and on smooth muscle tissue surrounding the collecting ducts. No difference in the distribution of NPR-A and NPR-B was observed between freshwater and seawater kidneys. Immunoreactivity was not observed in any tissue in which the antibodies had been preabsorbed. In addition, there was no difference in NPR-A and NPR-B mRNA expression between freshwater-acclimated and seawater-acclimated eels. These results suggest that, although utilizing the same second messenger system, ANP and CNP act on different targets within the kidney and presumably elicit different effects.
Assuntos
Anguilla/fisiologia , Guanilato Ciclase/metabolismo , Rim/fisiologia , Receptores do Fator Natriurético Atrial/metabolismo , Aclimatação , Animais , Western Blotting , Água Doce , Imuno-Histoquímica , Rim/anatomia & histologia , Modelos Biológicos , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Água do Mar , Equilíbrio HidroeletrolíticoRESUMO
Testicular spermatozoa and sperm development in the archaeogastropod Calliotropis glyptus Watson (Trochoidea: Trochidae) are examined using transmission electron microscopy and formalin-fixed tissues. During spermiogenesis, the acrosome, formed evidently through fusion of Golgi-derived proacrosomal vesicles, becomes deeply embedded in the condensing spermatid nucleus. Two centrioles (proximal and distal), both showing triplet microtubular substructure, are present in spermatids--the distal centriole giving rise to the sperm tail and its associated rootlet. During formation of the basal invagination in the spermatid nucleus, centrioles, and rootlet move towards the nucleus and come to lie totally within the basal invagination. Mitochondria are initially positioned near the base of the nucleus but subsequently become laterally displaced. Morphology of the mature spermatozoon is modified from that of the classic primitive or ect-aquasperm type by having 1) the acrosome embedded in the nucleus (the only known example within the Mollusca), 2) a deep basal invagination in the nucleus containing proximal and distal centrioles and an enveloping matrix (derived from the rootlet), 3) laterally displaced periaxonemal mitochondria, and 4) a tail extending from the basal invagination of the nucleus. Implantation of the acrosomal complex and centrioles within invaginations of the nucleus and lateral displacement of mitochondria effectively minimize the length of the sperm head and midpiece. Such modifications may be associated with motility demands, but this remains to be established. The unusual features of C. glyptus spermatozoa, though easily derivable from "typical" trochoid sperm architecture, may prove useful in delineating the genus Calliotropis or tracing its relationship to other genera within the trochid subfamily Margaritinae.
Assuntos
Acrossomo/ultraestrutura , Moluscos/anatomia & histologia , Espermatogênese , Espermatozoides/ultraestrutura , Animais , Masculino , Microscopia Eletrônica , Cauda do Espermatozoide/ultraestrutura , Espermátides/ultraestruturaRESUMO
Sperm ultrastructure in the rare deep-sea cephalopod Vampyroteuthis infernalis is described, based on formalin-fixed material held in the Australian Museum (Sydney). The species is the sole member of the coleoidean order Vampyromorpha, which represents a level of organization intermediate between that of the Sepioidea-Teuthoidea and the Octopoda. Spermatozoa of Vampyroteuthis, the simplest observed in any cephalopod, exhibit the following features: (1) a spheroidal acrosome lacking any complex substructure; (2) a short (8.5 microns) fusiform nucleus with a deep (2.2-2.5 microns) basal invagination (containing an extensive plug of dense material); (3) two triplet centrioles arranged parallel to the sperm longitudinal axis; (4) a short (1 micron) midpiece composed of a triangular cluster of mitochondria surrounding the centrioles; and (5) a tail (length 130-135 microns) that is continuous with one of the centrioles (here considered as a 'distal' centriole). An annulus and membranous skirt are absent, though the coarse fibres do fuse into a ring at the tail-midpiece junction). These cells show some resemblance to sperm or spermatids of sepioids and teuthoids (spheroidal acrosome, short nucleus) but are also remarkably similar to mid-spermatids of Octopus (with the exception of the uncondensed nucleus in Octopus spermatids). Sperm morphology supports the current assignment of Vampyroteuthis to a separate coleoidean order--Vampyromorpha--and also suggests that a close link exists between the Vampyromorpha and Octopoda.
Assuntos
Moluscos/fisiologia , Filogenia , Espermatozoides/ultraestrutura , Animais , Masculino , Microscopia Eletrônica , Octopodiformes/fisiologia , Especificidade da Espécie , EspermatogêneseRESUMO
Transcription of the sporulation gene spoVG of Bacillus subtilis is induced at the onset of spore formation and depends on the products of the regulatory genes spoOA, spoOB, and spoOH. We describe two effects of propagating the promoter region of spoVG on a multicopy plasmid replicon in B. subtilis cells. One effect is that transcription from the plasmid-borne spoVG promoter is altered with respect to the time of its induction and the dependence on spoO gene products. An example of this effect is that plasmid propagation was observed to relieve substantially the inhibitory effect of a mutation in spoOH, the spoO gene upon which spoVG promoter activity is most strongly dependent. We present results which suggest that propagation on a plasmid replicon causes an alteration in the conformation of spoVG promoter DNA which somehow compensates for the defective spoOH gene product. Plasmid propagation did not, however, entirely eliminate the requirement for the spoOH gene product; little or no spoVG-directed RNA synthesis was observed in cells bearing a putative spoOH deletion mutation, a finding which indicates that SpoOH protein plays an indispensable role in spoVG promoter utilization. Another effect of propagating the promoter region of spoVG on a multicopy plasmid is to inhibit sporulation. S1 nuclease mapping experiments suggest that amplification of spoVG on a multicopy plasmid causes the titration of a transcription factor or minor form of RNA polymerase holoenzyme required for utilization of one of the two overlapping promoters which comprise the spoVG transcription initiation region.
Assuntos
Bacillus subtilis/genética , Genes Bacterianos , Genes Reguladores , Plasmídeos , Regiões Promotoras Genéticas , Bacillus subtilis/fisiologia , Enzimas de Restrição do DNA , Genótipo , Esporos Bacterianos/fisiologiaRESUMO
This strategic plan translates the HCHP vision statement into a working plan for one major clinical condition--asthma in children. It is a working plan for clinicians and managers across specialties and levels. The results of the projects will improve in a measurable way significant clinical practice and outcomes, in keeping with the FY 1993 strategic goals.
Assuntos
Asma/terapia , Serviços de Saúde da Criança/normas , Sistemas Pré-Pagos de Saúde/normas , Gestão da Qualidade Total/organização & administração , Criança , Serviços de Saúde da Criança/organização & administração , Coleta de Dados , Conhecimentos, Atitudes e Prática em Saúde , Sistemas Pré-Pagos de Saúde/organização & administração , Hospitalização , Humanos , Massachusetts , Educação de Pacientes como Assunto/normas , Educação de Pacientes como Assunto/estatística & dados numéricos , Técnicas de PlanejamentoRESUMO
D-type cyclins (CycD) play key roles in linking the Arabidopsis cell cycle to extracellular and developmental signals, but little is known of their regulation at the post-transcriptional level or of their cyclin-dependent kinase (CDK) partners. Using new antisera to CycD2 and CycD3, we demonstrate that the CDK partner of these Arabidopsis cyclins is the PSTAIRE-containing CDK Cdc2a. Previous analysis has shown that transcript levels of CycD2 and CycD3 are regulated in response to sucrose levels and that both their mRNA levels and kinase activity are induced with different kinetics during the G(1) phase of cells reentering the division cycle from quiescence. Here we analyze the protein levels and kinase activity of CycD2 and CycD3. We show that CycD3 protein and kinase activity parallel the abundance of its mRNA and that CycD3 protein is rapidly lost from cells in stationary phase or following sucrose removal. In contrast to both CycD3 and the regulation of its own mRNA levels, CycD2 protein is present at constant levels. CycD2 kinase activity is regulated by sequestration of CycD2 protein in a form inaccessible to immunoprecipitation and probably not complexed to Cdc2a.
Assuntos
Proteínas de Arabidopsis , Arabidopsis/química , Proteína Quinase CDC2/química , Quinases Ciclina-Dependentes/metabolismo , Ciclinas/metabolismo , Fragmentos de Peptídeos/química , Western Blotting , Ciclina D3 , Cinética , Modelos Biológicos , Testes de Precipitina , Ligação Proteica , Biossíntese de Proteínas , RNA Mensageiro/metabolismo , Sacarose/farmacologia , Fatores de TempoRESUMO
The mechanisms by which plants modulate their growth rate in response to environmental and developmental conditions are unknown, but are presumed to involve specialized regions called meristems where cell division is concentrated. The possible role of cell division in influencing meristem activity and overall plant growth rate is controversial, with a prevailing view that cell division is secondary to higher order meristem controls. Here we show that a reduction in the length of the cell-cycle G1 phase and faster cell cycling occur when the rate of cell division in transgenic tobacco plants is increased by the plant D-type cyclin CycD2 (ref. 8). The plants have normal cell and meristem sizes, but elevated overall growth rates, an increased rate of leaf initiation and accelerated development in all stages from seedling to maturity. We conclude that cell division is a principal determinant of meristem activity and overall growth rate, and propose that modulation of plant growth rate is achieved through regulation of G1.
Assuntos
Ciclinas/fisiologia , Fase G1/fisiologia , Nicotiana/crescimento & desenvolvimento , Plantas Tóxicas , Proteínas Proto-Oncogênicas , Arabidopsis/genética , Divisão Celular/genética , Divisão Celular/fisiologia , Ciclina D , Quinase 4 Dependente de Ciclina , Quinases Ciclina-Dependentes/metabolismo , Ciclinas/genética , Fase G1/genética , Genes de Plantas , Meristema/fisiologia , Folhas de Planta/crescimento & desenvolvimento , Plantas Geneticamente Modificadas , Fatores de Tempo , Nicotiana/citologia , Nicotiana/enzimologia , Nicotiana/genética , Nicotiana/ultraestruturaRESUMO
The integrin alpha v beta 3 binds promiscuously to cell-adhesive proteins: vitronectin, fibronectin, and several others containing the RGD motif. We have explored molecular recognition by alpha v beta 3 through selection of ligands from large random libraries of peptides displayed on phage. Ligands bound by alpha beta 3 consisted primarily of RGD peptides; however, these peptides showed considerable heterogeneity with respect to the identities of amino acids flanking RGD. The tolerance of alpha v beta 3 for RGD peptides of diverse composition is consistent with its role in vivo as a versatile receptor for RGD-containing extracellular matrix proteins. Peptide ligands for alpha v beta 3 also included a novel binding sequence, identical to a tetrapeptide found in vitronectin, which is a candidate for a synergistic site in this adhesive protein that may act in concert with RGD to promote molecular recognition.
Assuntos
Proteínas da Matriz Extracelular/metabolismo , Integrinas/metabolismo , Oligopeptídeos/metabolismo , Receptores de Citoadesina/metabolismo , Sequência de Aminoácidos , Bacteriófagos , Sequência de Bases , Primers do DNA , Feminino , Humanos , Integrinas/isolamento & purificação , Dados de Sequência Molecular , Placenta/metabolismo , Gravidez , Ligação Proteica , Distribuição Aleatória , Receptores de Citoadesina/isolamento & purificação , Receptores de Vitronectina , Relação Estrutura-Atividade , Moldes GenéticosRESUMO
OBJECTIVE: To determine the perceived needs of perimenopausal women regarding the management of menopause and the resource needs of the clinicians who treat them. SETTING: A large staff and group network model health maintenance organization (HMO) in New England. PARTICIPANTS: A random sample of 790 perimenopausal women aged 45-60 years who were members of the HMO in 1991, and a random sample of 180 clinicians in internal medicine, family practice, and obstetrics/gynecology practicing in the HMO during 1991. METHOD: Mailed surveys of women and clinicians were designed to assess possible needs and attitudes that could lead to the improvement of care for menopausal women. The chi-square test was used to determine differences in perceived needs and satisfaction levels among women with differences in self-reported menopausal status. The Kruskal-Wallis one-way analysis of variance and the Mann-Whitney U test were used in the clinician survey to test for differences among specialties and between genders. RESULTS: The key findings include that: 1) most (81%) of the women wanted to see a woman clinician, 2) many (50%) were interested in a menopause support group, 3) 30% reported that their care for menopause had been fair to poor, 4) only 55% of the primary care specialists (including internal medicine and family practice) reported high confidence in their abilities to treat menopause, compared with 68% of the obstetric/gynecology clinicians, and 5) 56% of the clinicians surveyed said that support from the HMO to their practices for the treatment of menopause was fair to poor. CONCLUSIONS: There is an opportunity for better care for perimenopausal women as reported by two sources, HMO clinicians and members. To provide this care, clinicians may need explicit guidelines as well as administrative supports such as educational materials and specialty access. Since the capability for menopausal care from clinicians in obstetrics/gynecology is perceived to be higher than that from primary care clinicians, an opportunity for cross-specialty collaboration and training may exist.