The clinical significance of cysteine dioxygenase type 1 methylation in Barrett esophagus adenocarcinoma.

Methylation of cysteine dioxygenase type 1 (CDO1) gene, a tumor suppressor gene, has been studied in various cancers; however, there is no information regarding Barrett esophagus cancer. In this study, the clinical significance of CDO1 methylation in Barrett esophagus adenocarcinoma (BEA) was clarified. CDO1 gene promoter methylation was analyzed for DNA from the patient's specimens using quantitative methylation-specific polymerase chain reaction. Thirty-eight BEA patients who underwent resection were identified between 2000 and 2014. Hypermethylation of CDO1 gene was demonstrated to be frequently recognized even at early stage in BEA by quantitative methylation-specific polymerase chain reaction. In BEA, there is a robust prognostic difference between stage I and stage II/III/IV with regard to 5-year relapse-free survival (P = 0.0016) and 5-year overall survival (P = 0.0024), and the tumor size separated by 7 cm was also a prognostic factor. There was significant difference in CDO1 gene methylation according to the tumor size (P = 0.036). BEA patients with CDO1 gene methylation were shown marginally significantly poorer prognosis (P = 0.054) than otherwise patients. In conclusion, higher CDO1 gene methylation was seen in BEA at earlier stage than in squamous cell carcinoma, and it may account for aggressive phenotype of BEA.

TACR1 gene polymorphism and sex differences in postoperative nausea and vomiting.

We hypothesised that the genetic effect of single nucleotide polymorphisms in the TACR1 gene, which encodes NK1 receptors, could influence the sex difference in postoperative nausea and vomiting. Thirty-two selected single nucleotide polymorphisms were genotyped by the Sanger sequencing method in 200 patients who underwent lower abdominal surgery. The incidence and severity of postoperative nausea and vomiting were evaluated after surgery. The rs3755468-SNP showed significant association with the incidence and severity of postoperative nausea and vomiting (p = 0.016). The TT haplotype defined by two single nucleotide polymorphisms, including the rs3755468-SNP, was associated with reduced incidence and severity of postoperative nausea and vomiting in female patients (p = 0.03). The rs3755468-SNP is located within the predicted oestrogen response element and a DNase I hypersensitive site. The single nucleotide polymorphisms in the TACR1 gene are associated with sex differences in postoperative nausea and vomiting and may help to elucidate the mechanisms underlying these differences.

Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common form of human myelopathy caused by a compression of the spinal cord by ectopic ossification of spinal ligaments. To elucidate the genetic basis for OPLL, we have been studying the ttw (tiptoe walking; previously designated twy) mouse, a naturally occurring mutant which exhibits ossification of the spinal ligaments very similar to human OPLL (refs 3,4). Using a positional candidate-gene approach, we determined the ttw phenotype is caused by a nonsense mutation (glycine 568 to stop) in the Npps gene which encodes nucleotide pyrophosphatase. This enzyme regulates soft-tissue calcification and bone mineralization by producing inorganic pyrophosphate, a major inhibitor of calcification. The accelerated bone formation characteristic of ttw mice is likely to result from dysfunction of NPPS caused by predicted truncation of the gene product, resulting in the loss of more than one-third of the native protein. Our results may lead to novel insights into the mechanism of ectopic ossification and the aetiology of human OPLL.

Aerobic exercise attenuates pulmonary injury induced by exposure to cigarette smoke.

It has recently been suggested that regular exercise reduces lung function decline and risk of chronic obstructive pulmonary disease (COPD) among active smokers; however, the mechanisms involved in this effect remain poorly understood. The present study evaluated the effects of regular exercise training in an experimental mouse model of chronic cigarette smoke exposure. Male C57BL/6 mice were divided into four groups (control, exercise, smoke and smoke+exercise). For 24 weeks, we measured respiratory mechanics, mean linear intercept, inflammatory cells and reactive oxygen species (ROS) in bronchoalveolar lavage (BAL) fluid, collagen deposition in alveolar walls, and the expression of antioxidant enzymes, matrix metalloproteinase 9, tissue inhibitor of metalloproteinase (TIMP)1, interleukin (IL)-10 and 8-isoprostane in alveolar walls. Exercise attenuated the decrease in pulmonary elastance (p<0.01) and the increase in mean linear intercept (p=0.003) induced by cigarette smoke exposure. Exercise substantially inhibited the increase in ROS in BAL fluid and 8-isoprostane expression in lung tissue induced by cigarette smoke. In addition, exercise significantly inhibited the decreases in IL-10, TIMP1 and CuZn superoxide dismutase induced by exposure to cigarette smoke. Exercise also increased the number of cells expressing glutathione peroxidase. Our results suggest that regular aerobic physical training of moderate intensity attenuates the development of pulmonary disease induced by cigarette smoke exposure.

Enhanced clinical mastitis resistance in Holsteins with a FEZL p.Gly105(12_13) polymorphism.

Mastitis is a common infectious disease of the mammary gland and a major problem in the dairy industry. We previously reported that forebrain embryonic zinc finger-like (FEZL) encoding a stretch of 12 glycines (p.Gly105[12]) instead of 13 glycines (p.Gly105[13]) is associated with a lower somatic cell score (SCS) in a family derived from Walkway Chief Mark. Here we report that the p.Gly105[12] allele is associated with a significantly decreased incidence of clinical mastitis in a large Holstein population. We genotyped the FEZL polymorphism in 918 randomly collected Holstein sires, and investigated the effect of the polymorphism on the estimated breeding value (EBV) for SCS and milk, fat, solids-not-fat, and protein yield, and on the number of cattle with clinical mastitis among daughters derived from these sires. The average EBV for SCS among sires carrying the heterozygous p.Gly105[12] was significantly lower than that among sires carrying the homozygous p.Gly105[13], whereas we found no unfavorable effects of this polymorphism on EBV for milk, fat, solids-not-fat, and protein yield. The proportion of cows with clinical mastitis derived from sires carrying heterozygous p.Gly105[12] was significantly lower than that of daughters derived from sires carrying the homozygous p.Gly105[13]. Thus, selection of sires carrying p.Gly105[12] could be beneficial in the dairy industry by reducing the incidence of mastitis.

Degeneration of patellar cartilage in patients with recurrent patellar dislocation following conservative treatment: evaluation with delayed gadolinium-enhanced magnetic resonance imaging of cartilage.

OBJECTIVE: To examine the characteristics of cartilage degeneration in patients with recurrent patellar dislocation (RPD) following conservative treatment using delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC). DESIGN: This study evaluated three groups of knees: group I, 35 knees from both knees of patients with bilateral RPD and dislocated side knees of patients with unilateral RPD; group II, 15 non-dislocated side knees of patients with unilateral RPD; and group III, 20 knees from both knees of healthy volunteers. Differences in post-contrast T1 [T1(Gd)] of cartilage at both medial and lateral facets between groups I, II and III were analyzed. For group I, possible relationships were evaluated between T1(Gd) of cartilage and patient age, length of time between the initial dislocation and MRI and the total number of dislocations between the initial dislocation and MRI for both medial and lateral facets. RESULTS: The mean T1(Gd) of cartilage at medial facets for groups I, II and III were 411+/-46ms, 465+/-38ms and 490+/-29ms, respectively; there were significant differences between these means (P<0.05). The mean T1(Gd) of cartilage at lateral facets for groups I, II and III were 426+/-53ms, 466+/-45ms and 510+/-36ms, respectively; there were also significant differences between these means (P<0.05). Significant correlations were observed between T1(Gd) of cartilage for both medial and lateral facets and length of time between the initial dislocation and MRI (P<0.05). No other correlations were significant. CONCLUSION: dGEMRIC may be a useful method to monitor glycosaminoglycan concentration in patients with RPD following conservative treatment.

Diffuse type advanced gastric cancer showing dismal prognosis is characterized by deeper invasion and emerging peritoneal cancer cell: the latest comparative study to intestinal advanced gastric cancer.

BACKGROUND/AIMS: Diffuse type advanced gastric cancer (D-AGC) is highly malignant disorder with dismal prognosis, however the causative attribution explaining such malignancy remains fully unexplained as compared to intestinal type AGC (I-AGC). METHODOLOGY: We examined the archive of 232 AGC with cytology test (CY) but no distant metastasis, who underwent gastrectomy in Kitasato University Hospital in order to reveal the prognostic significance of D-AGC in a multivariate approach. RESULTS: D-AGC occupied 68% (157/232) among AGC, and showed poorer prognosis than I-AGC (p = 0.024). Multivariate prognostic analysis revealed that independent prognostic factors for AGC are CY (p < 0.0001), pN (p = 0.0068), pT (p = 0.015), and age (p = 0.012), and that histology was eliminated, suggesting that histology itself does not represent high malignancy within the identical stage. D-AGC was significantly associated with younger age (p = 0.018), female preponderance (p = 0.006), advanced pT (p = 0.0002), advanced pN (p = 0.016), and positive CY factors (p = 0.032), among which negative prognostic factors were pT, pN, and CY factors. Multivariate logistic regression analysis elucidated that both pT (serosal exposure, p = 0.013) and CY (p = 0.034) factors were finally remnant independent predictors for D-AGC among the 3 univariate negative prognostic factors, but that pN was not. Intriguingly, age could be an independent prognostic factor only in D-AGC. CONCLUSION: Our research revealed for the first time that more dismal prognosis of D-AGC than I-AGC could be explained by propensity of deeper invasion and emerging peritoneal cancer cell, and histology itself did not have a prognostic value, hence indicating that present staging system works properly even in D-AGC as well as I-AGC. We must identify its molecular mechanism of both invasion and emerging peritoneal disease of D-AGC in order to improve the prognosis.

Remarkable Improvement of Cardiac Function After Pre-emptive Kidney Transplant in a Patient With Severe Mitral Regurgitation Accompanied by Low Cardiac Function: A Case Report.

Patients with end-stage renal disease are at a high risk for cardiovascular diseases. It is controversial whether end-stage renal disease patients with low cardiac function can safely accept kidney transplant. Here, we present a 42-year-old kidney transplant recipient with severe mitral regurgitation accompanied by low cardiac function. He wanted to undergo a pre-emptive kidney transplant from his uncle. We decided to perform living kidney transplant prior to cardiac surgery. Despite adequate ultrafiltration and hemodiafiltration before operation, the patient's ejection fraction still remained 35% 1 day before transplant. He showed complete recovery of cardiac function in only 2 days after pre-emptive kidney transplant, although his body weight did not change before and after the operation. Early removal of the uremic toxin or inflammatory cytokines may play a role in rapid improvement of the cardiac function. Increase of vasoactive substances by improvement of kidney function may lead to reduction of afterload and amelioration of cardiac microcirculation. This report also suggests that optimal timing for operation might be important.

Cardiopulmonary exercise testing data processing and storage tools

ABSTRACT Conducting a clinical study is a complex and challenging task, so using technology to facilitate the process is necessary for the medical and scientific community. Data digitization is needed to store and process it. Digitization speeds up data visualization techniques so scientists can analyze it most effectively depending on their goals. In this project, we developed two digital tools related to the cardiopulmonary exercise test (CPET) data, one for digitizing PDF reports and the other for generating databases. The latter was a web-based database visualization dashboard. Users can select parameters of interest and check for differences among subgroups. Basic statistical tests are performed for each variable under analysis, and its results are presented in numerical and graphical formats. The initial statistical tests and the derived recommendation will guide the research team in deeper statistical analysis and robust analysis supporting more decisive conclusions. We ended up with the first version for both tools and validated it using patients' CPET data from the Dante Pazzanese Institute of Cardiology. We conducted a pilot study to verify if the tools served their purpose and observed that both programs worked as planned. The tools can be further tailored to be clinically or research-oriented. On the analysis of CPET's results, the conclusions for our example study were in line with what is presented in the bibliography for cardiorespiratory physiology.

Avaliação de setup para teste de elevação de pós-carga em pacientes com insuficiência cardíaca com fração de ejeção preservada: um estudo experimental / Evaluation of afterload elevation test setup in heart failure patients with preserved ejection fraction: an experimental study

INTRODUÇÃO: A Insuficiência Cardíaca com Fração de Ejeção Preservada (ICFEP) é uma doença de alta prevalência e de difícil diagnóstico devido ao fato que parte dos pacientes apresenta alterações apenas quando submetidos a determinadas condições de estresse hemodinâmico como elevação da pré-carga e da pós-carga do ventrículo esquerdo. OBJETIVOS: Avaliar a efetividade de um setup para elevação da pós-carga em pacientes com ICFEP. MÉTODOS: Realizou-se medida da pressão arterial sistólica (PAS), pressão arterial diastólica (PAD) e frequência cardíaca (FC) em repouso no membro superior direito com o paciente em decúbito supino seguindo as diretrizes da Sociedade Brasileira de Cardiologia. Em seguida, realizou-se um teste de elevação de pós-carga através da contração isométrica da mão esquerda com 60% da força máxima com um dinamômetro combinada com compressão pneumática de ambos os membros inferiores 20 mmHg acima da pressão sistólica utilizando dois esfigmomanômetros. Uma nova medida da pressão e frequência cardíaca foi realizada após 30s de início da manobra. Para comparação das métricas entre repouso e estresse, utilizou-se o teste-t pareado com intervalo de confiança de 95%. RESULTADOS: A população do estudo foi de 37 pacientes: 17 controles e 20 com ICFEP. A idade foi 58 ± 15 anos e 19 (51%) eram do sexo feminino. Houve diferença significativa para PAS: 128,2 ± 17,7 mmHg e 146,7 ± 19,9 mmHg (p<0,001) e FC 66 ± 11 bpm x 77 ± 14 bpm (p<0,001) repouso e estresse, respectivamente (Figura 1). CONCLUSÃO: O setup utilizado foi efetivo em elevar a pós-carga na população estudada. Os dados desta pesquisa têm grande potencial de aplicação para protocolos alternativos ao exercício padrão em cicloergômetro como teste provocativo para diagnóstico de ICFEP. Palavras-chaves: Insuficiência cardíaca com fração de ejeção preservada, Aumento de pós-carga, Teste de Estresse.

Teste de caminhada para caracterização de intolerância ao esforço de indivíduos com insuficiência cardíaca com fração de ejeção preservada: um estudo observacional / Walk test for characterization of exercise intolerance in individuals with heart failure with preserved ejection fraction: an observational study

INTRODUÇÃO: A Insuficiência Cardíaca com Fração de Ejeção Preservada (ICFEP) é uma condição clínica caracterizada por intolerância ao esforço e, nesse contexto, ferramentas que possam mensurar objetivamente este sintoma podem ser de grande valor na prática clínica. A abordagem diagnóstica atual da ICFEP requer aplicação de escores. O escore europeu HFA-PEFF, considera domínios morfológico, funcional e de peptídeos natriuréticos. Cada domínio tem um critério maior, que vale 2 pontos, e um critério menor, que vale 1 ponto. Se o total do escore for ≥ 5 pontos, o paciente tem diagnóstico de ICFEP. O teste de caminhada de seis minutos (TC6min) é uma ferramenta capaz de avaliar objetivamente a capacidade funcional traduzindo a habilidade dos pacientes em realizar tarefas cotidianas. OBJETIVOS: Avaliar a capacidade funcional de uma população de indivíduos em investigação para ICFEP. MÉTODOS: Trata-se de um estudo observacional transversal realizado em uma população de indivíduos com suspeita de ICFEP de um centro terciário de cardiologia. Foram incluídos sujeitos que realizaram o TC6min e categorizados de acordo com a probabilidade de ICFEP pelo escore HFA-PEFF. A normalidade dos dados foi avaliada pelo teste Shapiro-Wilk e a comparação entre os grupos foi realizada por meio do teste de Kruskal-Wallis. O nível de confiança adotado foi de 95%. Realizou-se ainda modelos de regressão linear univariado e multivariado. RESULTADOS: A amostra foi 105 indivíduos com idade de 59,5 ± 12,0 anos, 64% sexo feminino, IMC=31(5,8) Kg/m². A probabilidade de ICFEP foi baixa em 32 indivíduos, intermediária em 46; e alta em 27. A distância percorrida no TC6min foi de 416(±90) m. Para indivíduos com baixa probabilidade a distância percorrida foi de 472(±72) m, probabilidade intermediária de 406(±73) m e com alta probabilidade 356(±96) m. A diferença na distância percorrida entres os grupos com alta e baixa probabilidade de ICFEP foi estatisticamente significativa (P<0,05). Em um modelo de regressão multivariada, o efeito se manteve quando ajustado para idade, sexo e IMC. CONCLUSÃO: O presente estudo sugere que indivíduos com alta probabilidade de ICFEP classificados pelo escore HFA-PEF percorreram distâncias menores no TC6min quando comparados a indivíduos sem ICFEP (baixa probabilidade). Estes achados demonstram o valor clínico do TC6min na avaliação de indivíduos com suspeita de ICFEP. Palavras chaves: Insuficiência Cardíaca com Fração de Ejeção Preservada, Teste de Caminhada de Seis Minutos, Capacidade Funcional.

Treatment for developmental dysplasia of the hip using the Pavlik harness: long-term results.

We reviewed the medical records of 115 patients with 130 hips with developmental dysplasia with complete dislocation in the absence of a neuromuscular disorder, spontaneous reduction with a Pavlik harness, and a minimum of 14 years' follow-up. The mean age at the time of harness application was 4.8 months (1 to 12) and the mean time spent in the harness was 6.1 months (3 to 12). A total of 108 hips (83.1%) were treated with the harness alone and supplementary surgery for residual acetabular dysplasia, as defined by an acetabular index > 30 degrees , was performed in 22 hips (16.9%). An overall satisfactory outcome (Severin grade I or II) was achieved in 119 hips (91.5%) at a mean follow-up of 16 years (14 to 32) with a follow-up rate of 75%. Avascular necrosis of the femoral head was noted in 16 hips (12.3%), seven of which (44%) underwent supplementary surgery and nine (56%) of which were classified as satisfactory. The acetabular index was the most reliable predictor of residual acetabular dysplasia.

Input respiratory impedance in mice: comparison between the flow-based and the wavetube method to perform the forced oscillation technique.

Objective and approach: In this study, we estimated the constant phase model (CPM) parameters from the respiratory impedance of male BALB/c mice by performing the forced oscillation technique (FOT) in a control group (n = 8) and in a murine model of asthma (OVA) (n = 10). Then, we compared the results obtained by two different methods, using a commercial equipment (flexiVent-flexiWare 7.X; SCIREQ, Montreal, Canada) (FXV) and a wavetube method equipment (Sly et al 2003 J. Appl. Physiol. 94 1460-6) (WVT). We believe that the results from different methods may not be comparable. First, we compared the results performing a two-way analysis of variance (ANOVA) for the resistance, elastance and tissue damping. MAIN RESULTS: We found statistically significant differences in all CPM parameters, except for resistance, when comparing Control and OVA groups. When comparing devices, we found statistically significant differences in resistance, while differences in elastance were not observed. For tissue damping, the results from WVT were observed to be higher than those from FXV. Finally, when comparing the relative variation between the CPM parameters of the Control and OVA groups in both devices, no significant differences were observed for all parameters. SIGNIFICANCE: We then conclude that this assessment can compensate the effect of using different cannulas. Furthermore, tissue damping differences between groups can be compensated, since bronchoconstrictors were not used. Therefore, we believe that relative variations in the results between groups can be a comparing parameter when using different equipment without bronchoconstrictor administration.

Ferramentas para otimização de digitalização, armazenamento e visualização de dados do teste cardiopulmonar de exercício / Tools for optimizing the digitization, storage and visualization of cardiopulmonary exercise test data

INTRODUÇÃO: O teste cardiopulmonar de exercício (TCPE) é o padrão ouro para função cardiorrespiratória de pacientes. Por conta disso, os dados obtidos por meio deste são extremamente relevantes em pesquisas clínicas. No entanto, há situações em que, por conta de limitações dos equipamentos, a obtenção e armazenamento dos resultados destes exames se torna um processo complicado e dispendioso. OBJETIVO: Desenvolver ferramentas capazes de: 1) Digitalizar os dados nos formatos disponibilizados pelos equipamentos e montar um banco de dados; 2) Permitam uma análise, visualização e comparação otimizadas desses dados. MÉTODOS: Inicialmente, os laudos obtidos diretamente do equipamento são lidos por um programa, os valores dos parâmetros são armazenados durante os tempos mais relevantes do teste (limiares aeróbico e anaeróbico, VO2 máximo etc.) em um arquivo que servirá como banco de dados relacional. Esta base de dados é então utilizada para montar um Dashboard onde se pode selecionar a variável e o intervalo de tempo que se deseja comparar entre os grupos. Nele são mostrados histogramas e gráficos violinos para se comparar visualmente os grupos (figuras 1 e 2) e estatísticas dos dados coletados junto a: 1) Resultado de um teste de normalidade para o parâmetro escolhido; 2) Resultado (p-valor) de um teste de hipótese (paramétrico caso a distribuição seja considerada normal, ou não paramétrico caso contrário); 3) Os tamanhos mínimos que as amostras devem possuir para que os resultados dos testes possam ser considerados estatisticamente significativos. Por fim, é possível analisar, em uma segunda página desta ferramenta os valores individuais de cada paciente, sendo possível filtrar e visualizar apenas os valores dentro de um intervalo desejado. (Figura 4) RESULTADOS: As ferramentas desenvolvidas foram utilizadas na base de dados dos pacientes do Ambulatório de Medicina Cardiovascular Personalizada com os resultados de 102 exames. O Dashboard foi utilizado para realizar um estudo comparativo entre os pacientes homens e mulheres do ambulatório com resultados coerentes com a literatura. CONCLUSÕES: Com estas ferramentas foi possível, rapidamente, digitalizar e armazenar os dados montando um arquivo com as informações de todos pacientes. Ademais, também permitiu realizar um estudo exemplo comparando todos pacientes gerando imagens que auxiliam a visualizar os resultados e os respectivos p-valores para cada comparação.

Evaluation of vectorcardiography parameters matrixed synthesized

The form of analysis of the cardiac signal most used today is the electrocardiogram (ECG). However, in addition to this form of data visualization, there is the vectorcardiogram (VCG), that allows a visualization of the signal in 3 dimensions. This study aims to compare the different ECG to VCG transformation matrices Kors and Inverse Dower (iDower), by analyzing some known parameters taken from VCG's mathematically synthesized from 12-lead ECG's of amyloidosis patients. The idea is also to compare that similarity for patients with different types of amyloidosis. The study was done through the analysis of electrocardiograms taken from a sample of 12 humans who have amyloidosis, either mutant or wild-type. The results indicated that there is not much similarity between the signals, although the similarity was higher for patients with mutant amyloidosis than for those with wild-type amyloidosis.

Induction of unscheduled DNA synthesis in rat stomach mucosa by glandular stomach carcinogens.

Induction of unscheduled DNA synthesis (UDS) (repair DNA synthesis) in stomach pyloric mucosa of the F344/- DuCrj rat was examined in in vitro organ cultures in the presence of tritiated thymidine ([3H]dThd) and hydroxyurea after administration of chemical carcinogens in vivo. The DNA fraction was extracted from the cultured tissue, and the incorporation of [3H]dThd into DNA was determined in a liquid scintillation counter. DNA concentration was determined spectrophotometrically with either diphenylamine or 3,5- diaminobenzoic acid. A good correlation between induction of UDS and site specificity of carcinogens was observed. The glandular stomach carcinogens N-methyl-N'-nitro-N-nitrosoguanidine (CAS: 70-25-7), N-ethyl-N'-nitro-N-nitrosoguanidine (CAS: 63885-23-4), N-propyl-N'-nitro-N-nitrosoguanidine, 4-nitroquinoline 1-oxide (CAS: 56-57-5), and N-nitroso-N-methylurethane (CAS: 615-53-2) induced UDS in the pyloric mucosa of the stomach. UDS could be detected 2-4 hours after administration of carcinogens in vivo by the present method. The forestomach carcinogens 1-methyl-1-nitrosourea (CAS: 684-93-5) and aristolochic acid (CAS: 1398-06-7) and the nongastric carcinogens 2-acetylaminofluorene (CAS: 53-96-3), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole, 3-amino-1-methyl-5H-pyrido[4,3-b]indole, and dimethylnitrosamine (CAS: 62-75-9) did not induce UDS in the pyloric mucosa.

Análise de parâmetros do VCG obtidos a partir de matrizes de transformação do ECG em pacientes com hipertrofia cardíaca / Analysis of VCG parameters obtained from ECG transformation matrices in patients with cardiac hypertrophy

INTRODUÇÃO: O eletrocardiograma (ECG) é uma ferramenta diagnóstica primordial em cardiologia. Através de técnicas de pós-processamento do ECG digital é possível extrair dados do clássico vetorcardiograma (VCG) e ampliar as possibilidades do método. OBJETIVO: Comparar os dados matriciais do ECG entre os pacientes portadores de hipertrofia ventricular patológica (Cardiomiopatia Hipertrófica e Amiloidose Cardíaca) e o grupo controle utilizando duas matrizes diferentes de transformação de ECG para VCG: a matriz inversa de Dower (iDower) e a matriz de Kors. MÉTODOS: Foram analisados VCGs sintetizados a partir das duas matrizes, iDower e Kors, e tais exames foram obtidos para o grupo hipertrófico, composto por 11 pacientes, e para o grupo controle, com cinco pacientes. O tempo de coleta do ECG foi de 10 minutos e, para cada paciente, foram analisados 10 VCGs, referentes a cada minuto da coleta. Foram analisados a amplitude cúbica (mV), por meio da análise da variação dos valores, e o ângulo do complexo QRS e da onda T, por meio da análise de dados circulares. RESULTADOS: Em relação aos ângulos, as médias dos ângulos de cada grupo tiveram maior proximidade no grupo controle e menor no grupo hipertrófico. A variação destes ângulos foi maior utilizando a matriz de Kors para o grupo controle (Figura.1); no entanto, no grupo hipertrófico a maior variação no observada na matriz iDower (Figura 2). Em relação à amplitude cúbica das ondas, a variação foi pequena para ambos os grupos, porém com proximidade maior na onda T, e não houve diferença notável em relação às matrizes. CONCLUSÃO: Analisando as variáveis angulares e de amplitude cúbica nas ondas QRS e T para o grupo controle e hipertrófico, não foi observada diferença significativa entre os grupos. Tal proximidade entre as variáveis também foi observada considerando as matrizes de transformação.

Purification and characterization of recombinant hamster tissue complement C1s.

Hamster complement C1s cDNA was inserted into expression plasmid BCMGSNeo, and transfected to SEA7 cells, A31 mouse fibroblasts transformed by polyoma virus. The transfectant secreted a large amount of recombinant C1s that was activated in the serum free culture medium and hydrolyzed acetyl-Gly-L-Lys-naphthyl ester (AGLNE). C1s was purified to a homogeneity from the culture medium of the transfectant by DEAE-Sephadex, Dymatrex orange A and size-exclusion HPLC. Purified hamster C1s consumed human complement in hemolytic assay and hydrolyzed gelatin in enzymography. To investigate the enzymic action of C1s at molecular levels, several antibodies were prepared against hamster C1s. One peptide (amino-acid residues 379-391) and two peptides (amino-acid residues 478-496 and 560-583) corresponding to the heavy and the light chain, respectively, were synthesized. The amino-acid sequences of these regions is not conserved between hamster and human C1s. Antibodies against these peptides were raised in rabbits. The anti-peptide antibodies bound specifically to hamster serum and recombinant C1s but not to human C1s. They inhibited the esterase activity of recombinant C1s to varying degrees depending on each antibody's binding site.

Immune complex independent activation of complement, C1s secreted from hamster embryo malignant fibroblasts, Nil2C2 in serum free culture medium.

Antibody independent activation of complement C1s was examined by immunoblot analysis using an antibody against a synthetic peptide of hamster C1s L chain. Approx. 50% of C1s secreted from hamster embryo malignant fibroblasts Nil2C2 was functionally active in its two-chain form in the serum free culture medium. In contrast, no active C1s was found in a culture medium of hamster embryo fibroblasts (HEF). Active C1s was detectable, however, in the culture medium after HEF became a cell line. The immune complex independent activation of C1s was also observed in rat cell lines but not in secondary rat embryo fibroblasts. C1s in a membrane fraction of Nil2C2 was a proenzyme form and was not activated by incubation of the membrane itself suggesting that C1s was activated after secretion. The activation of C1s was not inhibited by human C1 inhibitor (C1-INH), benzamidine or soy bean trypsin inhibitor (SBTI) but was inhibited by leupeptin, nitrophenyl guanidinobenzoate and DFP. Our results suggest that C1s is activated either by a serine proteinase(s) other than those reported to cleave C1s or by an activator which directly stimulates autoactivation of C1s.