RESUMO
BACKGROUND: Sacituzumab govitecan (SG), a trophoblast cell surface antigen-2 (Trop-2)-directed antibody-drug conjugate, has demonstrated antitumor efficacy and acceptable tolerability in a phase I/II multicenter trial (NCT01631552) in patients with advanced epithelial cancers. This report summarizes the safety data from the overall safety population (OSP) and efficacy data, including additional disease cohorts not published previously. PATIENTS AND METHODS: Patients with refractory metastatic epithelial cancers received intravenous SG (8, 10, 12, or 18 mg/kg) on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. Endpoints for the OSP included safety and pharmacokinetic parameters with investigator-evaluated objective response rate (ORR per RECIST 1.1), duration of response, clinical benefit rate, progression-free survival, and overall survival evaluated for cohorts (n > 10 patients) of small-cell lung, colorectal, esophageal, endometrial, pancreatic ductal adenocarcinoma, and castrate-resistant prostate cancer. RESULTS: In the OSP (n = 495, median age 61 years, 68% female; UGT1A1∗28 homozygous, n = 46; 9.3%), 41 (8.3%) permanently discontinued treatment due to adverse events (AEs). Most common treatment-related AEs were nausea (62.6%), diarrhea (56.2%), fatigue (48.3%), alopecia (40.4%), and neutropenia (57.8%). Most common treatment-related serious AEs (n = 75; 15.2%) were febrile neutropenia (4.0%) and diarrhea (2.8%). Grade ≥3 neutropenia and febrile neutropenia occurred in 42.4% and 5.3% of patients, respectively. Neutropenia (all grades) was numerically more frequent in UGT1A1∗28 homozygotes (28/46; 60.9%) than heterozygotes (69/180; 38.3%) or UGT1A1∗1 wild type (59/177; 33.3%). There was one treatment-related death due to an AE of aspiration pneumonia. Partial responses were seen in endometrial cancer (4/18, 22.2% ORR) and small-cell lung cancer (11/62, 17.7% ORR), and one castrate-resistant prostate cancer patient had a complete response (n = 1/11; 9.1% ORR). CONCLUSIONS: SG demonstrated a toxicity profile consistent with previous published reports. Efficacy was seen in several cancer cohorts, which validates Trop-2 as a broad target in solid tumors.
Assuntos
Imunoconjugados , Neoplasias Pulmonares , Anticorpos Monoclonais Humanizados , Camptotecina/análogos & derivados , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A human immunodeficiency virus-1 (HIV-1)-positive male undergoing antiretroviral therapy was diagnosed with an axillary lymph node abscess caused by Corynebacterium ulcerans, and an environmental survey revealed that the patient's cat as the source of infection.
Assuntos
Abscesso/microbiologia , Síndrome da Imunodeficiência Adquirida/microbiologia , Doenças do Gato/microbiologia , Infecções por Corynebacterium/microbiologia , HIV-1/isolamento & purificação , Zoonoses/microbiologia , Abscesso/tratamento farmacológico , Abscesso/epidemiologia , Abscesso/virologia , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/epidemiologia , Animais , Antibacterianos/uso terapêutico , Antirretrovirais/uso terapêutico , Axila/microbiologia , Doenças do Gato/epidemiologia , Gatos , Corynebacterium/genética , Corynebacterium/isolamento & purificação , Infecções por Corynebacterium/tratamento farmacológico , Infecções por Corynebacterium/epidemiologia , Infecções por Corynebacterium/virologia , Humanos , Linfonodos/microbiologia , Masculino , Animais de Estimação/microbiologia , Zoonoses/tratamento farmacológico , Zoonoses/epidemiologia , Zoonoses/virologiaRESUMO
ONO-4641 is a next-generation sphingosine 1-phosphate (S1P) receptor agonist selective for S1P receptors 1 and 5. The objective of the study was to characterize the immunomodulatory effects of ONO-4641 using preclinical data. ONO-4641 was tested in both in-vitro pharmacological studies as well as in-vivo models of transient or relapsing-remitting experimental autoimmune encephalomyelitis (EAE). In vitro, ONO-4641 showed highly potent agonistic activities versus S1P receptors 1 and 5 [half maximal effective concentration (EC(50) ) values of 0·0273 and 0·334 nM, respectively], and had profound S1P receptor 1 down-regulating effects on the cell membrane. ONO-4641 decreased peripheral blood lymphocyte counts in rats by inhibiting lymphocyte egress from secondary lymphoid tissues. In a rat experimental autoimmune encephalomyelitis (EAE) model, ONO-4641 suppressed the onset of disease and inhibited lymphocyte infiltration into the spinal cord in a dose-dependent manner at doses of 0·03 and 0·1 mg/kg. Furthermore, ONO-4641 prevented relapse of disease in a non-obese diabetic mouse model of relapsing-remitting EAE. These observations suggest that ONO-4641 may provide therapeutic benefits in the treatment of multiple sclerosis.
Assuntos
Encefalomielite Autoimune Experimental/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Receptores de Lisoesfingolipídeo/agonistas , Animais , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Feminino , Contagem de Linfócitos , Linfócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos NOD , Ratos , Ratos Endogâmicos Lew , Medula Espinal/efeitos dos fármacosRESUMO
Digital nerve block is a common procedure with several techniques, including the traditional digital nerve block, transthecal digital nerve block, and single subcutaneous palmar digital nerve block. This review aimed to evaluate the efficacy of these three methods. A systematic search was performed in the PubMed, Scopus, and Cochrane Library databases. The risk of bias of the studies was assessed using the Cochrane Collaboration's tool for assessing the risk of bias and the Risk of Bias Assessment Tool for Non-Randomized Studies. Fourteen prospective randomized controlled studies and one prospective comparative study were included. The three methods of digital block showed similar onset times, durations, injection pain and incidence of incomplete anesthesia. This review confirmed that all three methods of digital block are equally effective. Considering that patients prefer a single injection and the potential risk of complications, the single subcutaneous digital block could be more widely used.
Assuntos
Anestésicos Locais , Bloqueio Nervoso , Humanos , Injeções Subcutâneas , Bloqueio Nervoso/métodos , Medição da Dor , Estudos ProspectivosRESUMO
Mucoepidermoid (MEC) salivary gland tumors arise from a t(11;19) rearrangement which generates a fusion oncogene, Mect1-Maml2, that functions to activate CREB-responsive target genes. To determine if sustained expression of Mect1-Maml2 is required for tumor cell growth, we first showed that ectopic expression of Mect1-Maml2 in rat epithelial RK3E cells is tumorigenic in vivo in nude mice and that excised xenografts continue to express the fusion oncogene. We then generated a hairpin RNAi vector that selectively suppressed the fusion peptide and showed that ectopic expression in either parotid or pulmonary MEC tumor cell lines containing the t(11;19) rearrangement resulted in at least 90% colony growth inhibition. In contrast, single nucleotide changes within this RNAi sequence abolished the ability to suppress Mect1-Maml2 protein and abolished all growth inhibition of these MEC tumor lines. In addition, the RNAi-specific vector had no effect on colony growth of non-MEC tumors including a lung tumor or two other salivary gland cell lines that do not express Mect1-Maml2. We also generated a mutant Mect1-Maml2 expression plasmid that carried silent nucleotide changes within the RNAi target sequence and observed that co-transfection of this mutant, but not wild-type Mect1-Maml2, could partially rescue RNAi growth inhibition in the MEC tumor line. The recent detection of acquired fusion oncogenes in epithelial solid tumors has suggested new possibilities for the diagnosis and therapy of these cancers. Our data show that the 'gain-of-function' activity from aberrant Mect1-Maml2 expression is a candidate therapeutic target for this group of malignant salivary gland tumors.
Assuntos
Divisão Celular/genética , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 19 , Proteínas de Fusão Oncogênica/fisiologia , Neoplasias das Glândulas Salivares/patologia , Translocação Genética , Sequência de Bases , DNA de Neoplasias , Humanos , Proteínas de Fusão Oncogênica/genética , Interferência de RNA , Neoplasias das Glândulas Salivares/genéticaRESUMO
Expression of MyoD, myogenin, MRF4, and Myf-5 converts nonmuscle cells to muscle cells. In an attempt to analyze the roles of these factors, we have investigated their effects on transcription driven by the promoter of the chicken myosin alkaline light-chain (MLC1) gene. The activation by CMD1 or c-myogenin (chicken MyoD or myogenin, respectively) was dependent on the existence of a muscle-specific regulatory region located from positions -2096 to -1743. Its distal half, containing a pair of E boxes (CANNTG), had been previously characterized as an enhancer responsive to CMD1 but not to c-myogenin. In this study, we report the identification of another enhancer in the muscle-specific regulatory region which is preferentially responsive to c-myogenin. Deletion and mutation analyses indicated that this enhancer requires a single E box and its flanking sequences. Furthermore, analysis of chimeric proteins of CMD1 and c-myogenin indicated that regions outside the basic helix-loop-helix domain of c-myogenin are involved in the specificity of the enhancer. These results show that CMD1 and c-myogenin act on the MLC1 gene by recognizing different upstream DNA sequences and that direct or indirect interactions between the regions outside the basic helix-loop-helix domain and flanking sequences of E boxes are involved in the target sequence specificity.
Assuntos
Galinhas/genética , Proteínas de Ligação a DNA , Elementos Facilitadores Genéticos , Proteína MyoD/metabolismo , Miogenina/metabolismo , Quinase de Cadeia Leve de Miosina/genética , Regiões Promotoras Genéticas , Transativadores , Fatores de Transcrição/metabolismo , Transcrição Gênica , Animais , Sequência de Bases , Células Cultivadas , Embrião de Galinha , Cloranfenicol O-Acetiltransferase/biossíntese , Cloranfenicol O-Acetiltransferase/metabolismo , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Dados de Sequência Molecular , Proteínas Musculares/metabolismo , Mutagênese Sítio-Dirigida , Proteína MyoD/biossíntese , Fator Regulador Miogênico 5 , Fatores de Regulação Miogênica/metabolismo , Miogenina/biossíntese , Oligodesoxirribonucleotídeos , Plasmídeos , Pele/metabolismo , Ativação Transcricional , TransfecçãoRESUMO
Case 1. Forty nine years woman was given a diagnosis of acute myocardial infarction. Coronary angiography and trans-esophageal echocardiography showed left main trunk dissection due to local aortic root dissection. We operated surgical repair at left main trunk by pericardium after percutaneous coronary intervention. Case 2. Forty nine years man was given a diagnosis of acute myocardial infarction caused by left main trunk dissection due to traumatic local aortic root dissection. We operated coronary artery bypass grafting after insertion of perfusion catheter to left main trunk for maintain coronary perfusion. Although local dissection of aortic aorta is relatively rare, it is potentially complicated with coronary malperfusion. We describe 2 success a cases of surgical treatment for local acute type A aortic dissection complicated with coronary malperfusion.
Assuntos
Angioplastia Coronária com Balão , Aneurisma Aórtico/cirurgia , Dissecção Aórtica/cirurgia , Doença das Coronárias/cirurgia , Infarto do Miocárdio/terapia , Dissecção Aórtica/complicações , Dissecção Aórtica/diagnóstico por imagem , Aorta/cirurgia , Aneurisma Aórtico/complicações , Aneurisma Aórtico/diagnóstico por imagem , Angiografia Coronária , Ponte de Artéria Coronária , Doença das Coronárias/etiologia , Ecocardiografia Transesofagiana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Procedimentos Cirúrgicos Vasculares/métodosRESUMO
Semen quality was determined in a sexually mature male Giant Panda, electroejaculated 13 times during a 5-year interval, before, during and after estrus of a female Giant Panda housed nearby. Testis volume and plasma testosterone concentrations were also measured. Mean testis volumes were 1223.0 +/- 64.7(S.E.M.)cm3 (before estrus), 1213.2 +/- 218.2 cm3 (during estrus), and 1360.2+/-160.4 cm3 (after estrus). Compared to before and during estrus in the female, testis volume decreased 70 days after estrus and there was no projectile ejaculation. The mean semen volume and sperm count were 2.2+/-0.7 mL and 8.3 +/- 3.1 x 10(8) before estrus, 2.4 +/- 0.9 mL and 5.7 +/- 0.9 x 10(8) during estrus, and 1.3 +/- 0.3 mL and 8.1 +/- 1.7 x 10(8) after estrus, respectively. The semen volume, sperm count, and testis volume markedly differed from 90 days before estrus until 66 days after estrus, whereas no marked differences in sperm motility, sperm viability, and proportion of morphologically abnormal spermatozoa were observed. Plasma testosterone concentrations were elevated both before and during estrus (0.62 +/- 0.23 ng/mL and 0.95 ng/mL), but decreased substantially after estrus (0.20 +/- 0.0 ng/mL). We inferred that spermatogenesis was active in this male panda from approximately 3 months before estrus to 2 months after estrus in the adjacent female.
Assuntos
Estro/fisiologia , Sêmen/fisiologia , Espermatozoides/fisiologia , Ursidae/fisiologia , Animais , Feminino , Masculino , Contagem de Espermatozoides/veterinária , Motilidade dos Espermatozoides/fisiologia , Espermatozoides/anormalidades , Testículo/anatomia & histologia , Testículo/fisiologia , Testosterona/sangueRESUMO
We isolated the novel cDNA gob-4, which was shown to be expressed in intestinal goblet cells. The deduced amino acid sequence is similar to the gene coding for the Xenopus laevis cement gland-specific XAG-2. These sequence and expression data suggest this gene may be involved in the secretory function.
Assuntos
Células Caliciformes/metabolismo , Intestino Delgado/metabolismo , Mucoproteínas/genética , Sequência de Aminoácidos , Animais , Camundongos , Dados de Sequência Molecular , Mucoproteínas/biossíntese , Proteínas OncogênicasRESUMO
Although p21 WAF1/Cip1 expression has been detected immunohistochemically in non-small cell lung cancer (NSCLC), the associations between p21 expression and clinical characteristics are unknown. To determine the association between p21 expression and clinical features, p21 expression was immunohistochemically analyzed in paraffin-embedded tumor samples from 137 patients with curatively resected NSCLC. p21 expression, indicating normal p21 function, was detected in 48 (35.0%) of the 137 patients with curatively resected NSCLC and was detected more frequently in patients with stage I or II disease (40.2%) than in those with stage IIIA disease (22.5%; P = 0.0483). There was no difference in the positive rate between squamous cell carcinoma [SCC; 15 of 48 (31.3%)] and adenocarcinoma [30 of 77 (39.0%)]. For SCC, patients with tumors expressing p21 survived longer than did those with tumors negative for p21 expression; however, the corresponding survival time was not significant for adenocarcinoma. On the other hand, p53 expression, detected in 58 (42.3%) of these patients, did not act as any predictor for prognosis in either SCC or adenocarcinoma. Our findings suggest that the presence of p21 expression is associated with favorable prognosis in SCC and may be useful in obtaining candidates for adjuvant therapies from among patients with SCC.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/mortalidade , Ciclinas/análise , Neoplasias Pulmonares/mortalidade , Proteínas de Neoplasias/análise , Adenocarcinoma/química , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Adulto , Idoso , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Carcinoma Adenoescamoso/química , Carcinoma Adenoescamoso/genética , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/terapia , Carcinoma de Células Grandes/química , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/mortalidade , Carcinoma de Células Grandes/terapia , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Ciclo Celular , Quimioterapia Adjuvante , Terapia Combinada , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/biossíntese , Ciclinas/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Tábuas de Vida , Neoplasias Pulmonares/química , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Pneumonectomia , Prognóstico , Análise de SobrevidaRESUMO
We cloned the full-length cDNA of max gene from the common carp (Cyprinus carpio). The cDNA clone of carp max consists of 1209 bp and contained an ATG-initiated ORF consisting of 156 aa. The carp MAX share 76.7-93.8% aa identity with those of human, mouse, rat, chicken, Xenopus and zebrafish, respectively. The 15 bp alternative splicing was observed in the loop region of helix-loop-helix and is not previously described in mammalian max sequences. Transcripts of max gene were observed in all of the tissues of carp investigated in this study. The highest expression was found in the ovary, and the transcripts in hepatopancreas and heart were low. Two carp c-myc genes (CAM1 and CAM2) showed differential expression pattern. The expression of max was concomitant with CAM2 expression, but not with CAM1. It has been reported that MYC/MAX heterodimer as a regulator of gene expression has been maintained throughout vertebrate evolution, and the expression of c-myc has been concomitant with max expression. In addition, according to phylogenetic analysis, CAM1 is evolving faster than CAM2 after gene duplication. Therefore, this result suggests that CAM1 may evolve to obtain a new function different from c-myc.
Assuntos
Carpas/genética , Proteínas de Ligação a DNA/genética , Genes myc , Sequências Hélice-Alça-Hélice , Zíper de Leucina , Fatores de Transcrição/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Fatores de Transcrição de Zíper de Leucina Básica , DNA Complementar , Perfilação da Expressão Gênica , Humanos , Dados de Sequência Molecular , Homologia de Sequência de AminoácidosRESUMO
We determined the heterogeneous transcription start points (tsp) of two c-myc genes from the common carp (Cyprinus carpio), tetraploid teleost, by the oligo-capping method and showed the existence of the first exon. This is the first report on the existence of the first exons of the fish c-myc gene. Transcription of the two carp c-myc genes started from at least four sites in CAM1, locating from -752 to -381bp upstream of the translation start site, and from 12 sites in CAM2, locating from -586 to -413bp upstream respectively. The first introns of CAM1 and CAM2 were deduced to be 335 and 356bp, respectively. They shared 86.9% nt identity, lower than those of the second exons (94.1%), and third exons (92.3%), which suggest that the first exons evolved faster. No nt identities were found between the c-myc first exons of carp and other vertebrates. The putative promoter regions in CAM1 and CAM2 contained no obvious TATA or CCAAT boxes in the expected positions.
Assuntos
Carpas/genética , Genes myc/genética , Animais , Sequência de Bases , Éxons , Íntrons , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Isoformas de Proteínas/genética , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência do Ácido Nucleico , Transcrição GênicaRESUMO
The cDNA sequence coding for the coat protein of cucumber mosaic virus (Japanese Y strain) was cloned, and its nucleotide sequence was determined. The sequence contains an open reading frame that encodes the coat protein composed of 218 amino acids. The nucleotide and deduced amino acid sequences of the coat protein of this strain were compared with those of the Q strain; the homologies of the sequences were 78% and 81%, respectively. Further study of the sequences gave an insight into the genome organization and the molecular features of the coat protein. The coding region can be divided into three characteristic regions. The N-terminal region has conserved features in the positively charged structure, the hydropathy pattern and the predicted secondary structure, although the amino acid sequence is varied mainly due to frameshift mutations. It is noteworthy that the positions of arginine residues in this region are highly conserved. Both the nucleotide and amino acid sequences of the central region are well conserved. The amino acid sequence of the C-terminal region is not conserved, because of frameshift mutations, however, the total number of amino acids is conserved. The nucleotide sequence of the 3'-noncoding region is divergent, but it could form a tRNA-like structure similar to those reported for other viruses. Detailed investigation suggests that the Y and Q strains are evolutionarily distant.
Assuntos
Capsídeo/genética , DNA Viral/genética , Genes Virais , Vírus do Mosaico/genética , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , DNA/genética , Dados de Sequência Molecular , Conformação de Ácido Nucleico , RNA de Transferência/genética , RNA Viral/genéticaRESUMO
A new series of sulfonic acids were synthesized and tested for their enkephalinase inhibitory activity. Among them, the most potent was N-(2-benzyl-3-mercaptopropionyl)metanilic acid 10i with an IC50 value of 0.27 nM. Several other analogues (10a,b,j,n,o,gg,hh) showed the inhibitory activity comparable to or greater than thiorphan (IC50 = 2.6 nM), a C-terminal carboxyl-containing inhibitor of enkephalinase. Thus compounds containing a C-terminal sulfo group, instead of the C-terminal carboxyl group, were found to show a remarkably high level of inhibition of enkephalinase. The analgesic activity of 10b, (S)-10b, and (R)-10b was also evaluated by the phenylbenzoquinone writhing test.
Assuntos
Neprilisina/antagonistas & inibidores , Analgésicos/farmacologia , Animais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Feminino , Camundongos , Conformação Molecular , Coelhos , Relação Estrutura-Atividade , Ácidos Sulfônicos/síntese química , Ácidos Sulfônicos/farmacologiaRESUMO
To investigate the prognostic role of hTERT expression in non-small cell lung cancer (NSCLC), we examined the expression of hTERT mRNA in tumor specimens from 68 patients with NSCLC using RT-PCR. The expression of hTERT was detected in 34 (50%) of 68 cancer tissues. There were no correlations between hTERT status and any common clinical features except age. Patients with hTERT expression had shorter survival than those without hTERT expression. Multivariate analysis showed that hTERT expression was an independent negative prognostic factor. These results suggest that expression of hTERT may be an independent prognostic factor for NSCLC patients.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , RNA , Telomerase/metabolismo , Idoso , Análise de Variância , Proteínas de Ligação a DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Absence of consensus persists regarding the optimal procedure and timing for the surgical treatment of young infants with symptomatic tetralogy of Fallot. From 1987 through 1992, 56 patients with tetralogy of Fallot were operated on at less than 6 months of age. Forty-one patients (median age 2.9 months) underwent primary repair and 15 (median age 2.4 months) underwent initial palliation. Mean follow-up was 24.2 +/- 16.4 months. No strict protocol was used but patients who received initial palliation were younger, had a smaller pulmonary arterial tree, or had anomalous coronary artery. Two patients died (overall mortality 3.6%; 95% confidence limits 0% to 11%), one after initial palliation (6.7%), and one after primary repair (2.4%) (P = 0.47). Eight of the 15 patients who received initial palliation underwent repair and had an increase in pulmonary anulus size at the time of definitive repair (mean difference Z-value = 2.2 +/- 1.6 standard deviation; p = 0.006). Transannular patch was required in 50% of patients who underwent repair (56% among patients having primary repair versus 13% for patients having initial palliation; P = 0.03). Five patients underwent reoperation. Early primary repair of symptomatic tetralogy of Fallot was achieved with a low mortality rate and is the preferred protocol. Initial palliation remains indicated in case of associated cardiac anomaly, very low weight, or severely hypoplastic pulmonary artery tree.
Assuntos
Cuidados Paliativos , Tetralogia de Fallot/cirurgia , Fatores Etários , Prótese Vascular , Seguimentos , Humanos , Lactente , Modelos Logísticos , Politetrafluoretileno , Próteses e Implantes , Reoperação , Taxa de Sobrevida , Tetralogia de Fallot/mortalidade , Fatores de TempoRESUMO
Fifty-six consecutive patients underwent total correction of truncus arteriosus. Median age at repair was 41 days, with a range of 2 days to 8 months. In 71% the operation was done in the first 2 months of life. Nine patients had complex forms of truncus and 11 patients had aortic insufficiency. The truncal aortic root was transected, which provides a clear exposure of the coronary ostia. The aorta was reconstructed by direct end-to-end anastomosis, and the truncal valve was preserved in every case. Several different techniques were used for pulmonary reconstruction, including three types of anatomic reconstruction of the pulmonary valve with a trisigmoid leaflet system and two types of nonanatomic reconstruction. The anatomic techniques included use of 33 Dacron valved conduits, eight homograft valved conduits, and one porcine aortic root bioprosthesis. The nonanatomic reconstructions included direct anastomosis to the right ventricle in nine patients and insertion of autologous pericardial valved conduits in five. The hospital mortality was 16% (9/56; 95% confidence limits, 2% to 30%). Multivariate analysis outlines two independent incremental risk factors for hospital death: nonanatomic pulmonary valve reconstruction techniques and age younger than 1 month. The hospital mortality was 7.1% in the group with anatomic pulmonary valve reconstruction versus 43% in the group with nonanatomic pulmonary valve reconstruction (p = 0.015). The hospital mortality was 5.7% in those older than 1 month versus 33% in those younger than 1 month of age (p = 0.04). There were two late deaths. The actuarial freedom from reoperation and angioplasty at 7 years was 100% for patients receiving pericardial conduits, 80% for those undergoing direct anastomosis, 77% for those receiving Dacron conduits, and only 43% for those receiving homografts (p = 0.02). In conclusion, anatomic reconstruction of the pulmonary valve seems important at the time of the operation, age younger than 1 month remains an incremental risk factor, and the truncal valve can be preserved.
Assuntos
Próteses e Implantes , Persistência do Tronco Arterial/cirurgia , Fatores Etários , Insuficiência da Valva Aórtica/cirurgia , Bioprótese , Procedimentos Cirúrgicos Cardíacos/métodos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Mortalidade Hospitalar , Humanos , Lactente , Recém-Nascido , Valva Pulmonar/cirurgia , Reoperação , Estudos Retrospectivos , Fatores de Risco , Persistência do Tronco Arterial/mortalidade , Função Ventricular Direita , Obstrução do Fluxo Ventricular Externo/cirurgiaRESUMO
A 7-year-old boy with acute encephalitis was proved to have Coxiella burnetii infection. Cerebrospinal fluid but not serum had elevated values of interleukins 1-beta and 6, but not of tumor necrosis factor.
Assuntos
Coxiella burnetii/isolamento & purificação , Citocinas/líquido cefalorraquidiano , Encefalite/diagnóstico , Febre Q/diagnóstico , Anticorpos Antibacterianos/sangue , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/microbiologia , Cerebelo/patologia , Líquido Cefalorraquidiano/citologia , Líquido Cefalorraquidiano/imunologia , Líquido Cefalorraquidiano/microbiologia , Criança , Coxiella burnetii/genética , Coxiella burnetii/imunologia , Citocinas/sangue , Encefalite/imunologia , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Imageamento por Ressonância Magnética , Masculino , Reação em Cadeia da Polimerase , Febre Q/imunologia , Telencéfalo/patologiaRESUMO
Troponin T (TNT) expressed in the developing chicken cardiac muscle was examined by immunoblotting combined with two-dimensional electrophoresis (2-D PAGE) and peptide mapping. When the whole lysate of the neonatal heart was examined by 2-D PAGE, two TNT variants were detected on the gel by monoclonal antibody to TNT. Expression of the two variants was developmentally regulated: one isoform (type I) was expressed from embryonic through neonatal stages, and the other (type II) from the late embryonic stage through adulthood during cardiac muscle development. The type-I isoform, but not type-II isoform, was also expressed transiently in chicken skeletal muscle at embryonic stages. As judged from the peptide maps, the two isoforms differed in the N-terminal region but not in the C-terminal region.
Assuntos
Variação Genética , Coração/crescimento & desenvolvimento , Troponina/genética , Envelhecimento , Animais , Anticorpos Monoclonais , Embrião de Galinha , Eletroforese em Gel de Poliacrilamida , Coração/embriologia , Mapeamento de Peptídeos , Troponina/análise , Troponina TRESUMO
Mitochondria have two independent protein-import machineries, one in the outer membrane (the Tom system) and the other in the inner membrane (the Tim system). Here, we have characterized the initial steps of precursor import into rat liver mitoplasts. The import reaction was separated into two stages, consisting of precursor binding to the mitoplasts at 0-10 degreesC, and a subsequent chase reaction at 30 degreesC. This assay revealed four distinct precursor-import steps: DeltaPsi-dependent initial binding of the precursor, precursor transfer to the Tim23-Tim17 stage, DeltaPsi-dependent translocation of the presequence across the inner membrane, and the complete translocation of the mature portion of the precursor. Antibodies against the intermembrane space domain of Tim23 inhibited neither the precursor binding nor the subsequent translocation of the presequence across the inner membrane. In contrast, the antibodies inhibited the complete translocation of the mature domain of the precursor across the inner membrane. Immunoprecipitation with anti-Tim23 IgGs revealed that the precursor-Tim23 complex increased with time and temperature after the initial targeting of the precursor to the mitoplasts. These results suggest that the precursor is first targeted to the inner membrane component DeltaPsi-dependently, then transferred to the Tim system consisting of Tim23-Tim17, and finally imported into the matrix.