RESUMO
OBJECTIVES: We studied the clinical and genetic features of hypertrophic cardiomyopathy (HCM) caused by mutations in the myosin-binding protein C gene (MYBPC3) in 110 consecutive, unrelated patients and family members of European descent. BACKGROUND: Mutations in the MYBPC3 gene represent the cause of HCM in approximately 15% of familial cases. MYBPC3 mutations were reported to include mainly nonsense versus missense mutations and to be characterized by a delayed onset and benign clinical course of the disease in Japanese and French families. We investigated the features that characterize MYBPC3 variants in a large, unrelated cohort of consecutive patients. METHODS: The MYBPC3 gene was screened by single-strand conformational polymorphism analysis and sequencing. The clinical phenotypes were analyzed using rest and 24-h electrocardiography, electrophysiology, two-dimensional and Doppler echocardiography and angiography. RESULTS: We identified 13 mutations in the MYBPC3 gene: one nonsense, four missense and three splicing mutations and five small deletions and insertions. Of these, 11 were novel, and two were probably founder mutations. Patients with MYBPC3 mutations presented a broad range of phenotypes. In general, the 16 carriers of protein truncations had a tendency toward earlier disease manifestations (33 +/- 13 vs. 48 +/- 9 years; p = 0.06) and more frequently needed invasive procedures (septal ablation or cardioverter-defibrillator implantation) compared with the 9 carriers of missense mutations or in-frame deletions (12/16 vs. 1/9 patients; p < 0.01). CONCLUSIONS: Multiple mutations, which include missense, nonsense and splicing mutations, as well as small deletions and insertions, occur in the MYBPC3 gene. Protein truncation mutations seem to cause a more severe disease phenotype than missense mutations or in-frame deletions.
Assuntos
Cardiomiopatia Hipertrófica/genética , Proteínas de Transporte/genética , Mutação , Adolescente , Adulto , Idoso , Cardiomiopatia Hipertrófica/diagnóstico , Estudos de Coortes , Saúde da Família , Feminino , Efeito Fundador , Variação Genética , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , FenótipoRESUMO
Magnetic analyses of hippocampal material from deceased normal and epileptic subjects, and from the surgically removed epileptogenic zone of a living patient have been carried out. All had magnetic characteristics similar to those reported for other parts of the brain [6]. These characteristics along with low temperature analysis indicate that the magnetic material is present in a wide range of grain sizes. The low temperature analysis also revealed the presence of magnetite through manifestation of its low temperature transition. The wide range of grain sizes is similar to magnetite produced extracellularly by the GS-15 strain of bacteria and unlike that found in magnetotactic bacteria MV-1, which has a restricted grain size range. Optical microscopy of slices revealed rare 5-10 micron clusters of finer opaque particles, which were demonstrated with Magnetic Force Microscopy to be magnetic. One of these was shown with EDAX to contain AI, Ca, Fe, and K, with approximate weight percentages of 55, 19, 19, and 5, respectively.
Assuntos
Epilepsia/metabolismo , Hipocampo/química , Epilepsia/fisiopatologia , Óxido Ferroso-Férrico , Hipocampo/fisiologia , Hipocampo/fisiopatologia , Humanos , Ferro , Magnetismo , Óxidos , Valores de Referência , TemperaturaAssuntos
Traumatismos Abdominais/complicações , Peritonite/etiologia , Adolescente , Adulto , Diagnóstico Diferencial , Feminino , Fraturas Ósseas/complicações , Hemorragia/diagnóstico , Humanos , Rim/lesões , Laparotomia , Masculino , Métodos , Pessoa de Meia-Idade , Pelve/lesões , Peritonite/diagnóstico , Peritonite/terapia , Ruptura/diagnóstico , Baço/lesões , Esplenectomia , Ruptura Esplênica/diagnóstico , Uretra/lesões , Bexiga Urinária/lesõesRESUMO
Two cases of a psudoatresia of the gallbladder are referated. Only by intraoperative cholangiography the real situation could be shown. Without any exception this radiological method should be used in all operations of the biliary system.
Assuntos
Colangiografia , Vesícula Biliar/anormalidades , Adolescente , Idoso , Colecistectomia , Colelitíase/diagnóstico por imagem , Colelitíase/cirurgia , Feminino , Humanos , MasculinoRESUMO
A review of 603 cases of carcinoma of the bronchi is given. Symptoms, diagnosis and therapy are discussed. The five year survival-rate is 22%. The problem of early diagnosis is pointed out.
Assuntos
Neoplasias Brônquicas , Adulto , Fatores Etários , Idoso , Neoplasias Brônquicas/diagnóstico , Neoplasias Brônquicas/patologia , Neoplasias Brônquicas/cirurgia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Osteoartropatia Hipertrófica Secundária/complicações , Fatores de TempoRESUMO
1752 cases of colon carcinoma are reviewed. History and characteristics of these tumors are described and the results of operative therapy are shown. 50% of the curatively operated patients were still alive after five years, and it seems especially important to think of the possibility of such a carcinoma. Most of our cases have shown early symptoms. It is necessary to interrogate every patient in this respect.
Assuntos
Neoplasias do Colo/terapia , Adulto , Idoso , Anemia/etiologia , Doenças Cardiovasculares/etiologia , Neoplasias do Colo/mortalidade , Neoplasias do Colo/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peritonite/etiologia , Pneumonia/etiologia , Complicações Pós-Operatórias , Embolia Pulmonar/etiologia , CicatrizaçãoRESUMO
We report on an extensive study of the influence of spin anisotropy on spin glass aging dynamics. New temperature cycle experiments allow us to compare quantitatively the memory effect in four Heisenberg spin glasses with various degrees of random anisotropy and one Ising spin glass. The sharpness of the memory effect appears to decrease continuously with the spin anisotropy. Besides, the spin glass coherence length is determined by magnetic field change experiments for the first time in the Ising sample. For three representative samples, from Heisenberg to Ising spin glasses, we can consistently account for both sets of experiments (temperature cycle and magnetic field change) using a single expression for the growth of the coherence length with time.
RESUMO
BACKGROUND: The existence of a constitutively expressed machinery for death in individual cells has led to the notion that survival factors repress this machinery and, if such factors are unavailable, cells die by default. In many cells, however, mRNA and protein synthesis inhibitors induce apoptosis, suggesting that in some cases transcriptional activity might actually impede cell death. To identify transcriptional mechanisms that interfere with cell death and survival, we combined gene trap mutagenesis with site-specific recombination (Cre/loxP system) to isolate genes from cells undergoing apoptosis by growth factor deprivation. RESULTS: From an integration library consisting of approximately 2 x 106 unique proviral integrations obtained by infecting the interleukin-3 (IL-3)-dependent hematopoietic cell line - FLOXIL3 - with U3Cre gene trap virus, we have isolated 125 individual clones that converted to factor independence upon IL-3 withdrawal. Of 102 cellular sequences adjacent to U3Cre integration sites, 17% belonged to known genes, 11% matched single expressed sequence tags (ESTs) or full cDNAs with unknown function and 72% had no match within the public databases. Most of the known genes recovered in this analysis encoded proteins with survival functions. CONCLUSIONS: We have shown that hematopoietic cells undergoing apoptosis after withdrawal of IL-3 activate survival genes that impede cell death. This results in reduced apoptosis and improved survival of cells treated with a transient apoptotic stimulus. Thus, apoptosis in hematopoietic cells is the end result of a conflict between death and survival signals, rather than a simple death by default.
Assuntos
Apoptose/genética , Sobrevivência Celular/genética , Regulação da Expressão Gênica , Células 3T3 , Animais , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Vetores Genéticos/genética , Interleucina-3/farmacologia , Camundongos , Análise de Sequência com Séries de OligonucleotídeosRESUMO
A new in situ microscope (ISM) was developed and tested to perform in-line monitoring of average cell volume and cell concentration in agitated cultures subjected to osmotic stress. The ISM is directly immersed into the agitated broth in a bioreactor and generates still images of cells by using pulsed luminescent diode illumination and a virtual probe volume defined by depth of focus. This technique allows the acquisition of microscopic still images without mechanical sampling techniques. The front end of the sensor fits into a standard 25-mm port and it can be steam sterilized together with the bioreactor. The automatic image evaluation generates signals of the cell concentration and the average cell volume with a time resolution of a few minutes per data point (if a 200 MHz PC is used). Without the need for evaluation, the images can be acquired and stored at a rate of one image per 0.6 s. Hansenula anomala was cultivated as batch fermentation and monitored inline with the ISM. The ISM signal of the cell concentration agreed well with referential growth curves that were obtained from counting with a hemocytometer. The ISM signal of the average cell volume shows a gradual volume reduction as a result of the aging of the culture, and it monitors an abrupt and strong cell contraction if osmotic shocks are generated in the bioreactor. Systematic in vitro studies of osmotic shocks were performed by applying the ISM to agitated culture samples of H. anomala. The volume signal of H. anomala during osmotic shocks showed a very fast cell contraction within less than a second. Within half an hour after the shocks, no signal drifts were observed, which would indicate volume restoration. These findings suggest that the ISM volume signal can be used as an inline indicator of osmotic stress in cell cultures.