RESUMO
The four main cell functions, proliferation, apoptosis, differentiation and migration, are tightly regulated by external signals that initiate intracellular signal transduction pathways and determine the cellular behaviour. The concentration and composition of such external signals are at least important for the decision of cells as to which function has to be executed. Interleukin-8 is a well known inducing signal for neutrophil granulocyte migration, while the epidermal growth factor is an inducing signal for breast carcinoma cell migration. Depending on the concentrations of interleukin-8, the neutrophil granulocytes are capable of migration. However, at high concentration of interleukin-8 the migratory activity of each single cell is reduced, indicating that high concentrations of the chemokine inhibit migration and promote the performance of other cell functions. Concerning breast carcinoma cells, the epidermal growth factor is not only an inducer of migration but also an inhibitor of proliferation. These two examples provide evidence for a dose dependent action of external signals for several cell functions in parallel. This versatility of the effects of one ligand might be based on several intracellular signal transduction pathways that are turned on. For the dose-dependent differences of the effect of interleukin-8 we propose a two wheel model of an inositolphosphate-mediated, ATP-independent release of calcium from intracellular stores and a cyclic AMP-mediated, ATP-dependent uptake of calcium into the endoplasmatic reticulum.
Assuntos
Fenômenos Fisiológicos Celulares/efeitos dos fármacos , Quimiotaxia de Leucócito/efeitos dos fármacos , Fator de Crescimento Epidérmico/farmacologia , Interleucina-8/farmacologia , Neutrófilos/efeitos dos fármacos , Adenocarcinoma/patologia , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Neoplasias da Mama/patologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Quimiotaxia de Leucócito/fisiologia , Citometria de Fluxo , Humanos , Microscopia de Vídeo , Neutrófilos/fisiologia , Células Tumorais CultivadasRESUMO
The four main cell functions, proliferation, apoptosis, differentiation and migration, are tightly regulated by external signals that initiate intracellular signal transduction pathways and determine the cellular behaviour. The concentration and composition of such external signals are at least important for the decision of cells as to which function has to be executed. Interleukin-8 is a well known inducing signal for neutrophil granulocyte migration, while the epidermal growth factor is an inducing signal for breast carcinoma cell migration. Depending on the concentrations of interleukin-8, the neutrophil granulocytes are capable of migration. However, at high concentration of interleukin-8 the migratory activity of each single cell is reduced, indicating that high concentrations of the chemokine inhibit migration and promote the performance of other cell functions. Concerning breast carcinoma cells, the epidermal growth factor is not only an inducer of migration but also an inhibitor of proliferation. These two examples provide evidence for a dose dependent action of external signals for several cell functions in parallel. This versatility of the effects of one ligand might be based on several intracellular signal transduction pathways that are turned on. For the dose-dependent differences of the effect of interleukin-8 we propose a two wheel model of an inositolphosphate-mediated, ATP-independent release of calcium from intracellular stores and a cyclic AMP-mediated, ATP-dependent uptake of calcium into the endoplasmatic reticulum.
RESUMO
The four main cell functions, proliferation, apoptosis, differentiation and migration, are tightly regulated by external signals that initiate intracellular signal transduction pathways and determine the cellular behaviour. The concentration and composition of such external signals are at least important for the decision of cells as to which function has to be executed. Interleukin-8 is a well known inducing signal for neutrophil granulocyte migration, while the epidermal growth factor is an inducing signal for breast carcinoma cell migration. Depending on the concentrations of interleukin-8, the neutrophil granulocytes are capable of migration. However, at high concentration of interleukin-8 the migratory activity of each single cell is reduced, indicating that high concentrations of the chemokine inhibit migration and promote the performance of other cell functions. Concerning breast carcinoma cells, the epidermal growth factor is not only an inducer of migration but also an inhibitor of proliferation. These two examples provide evidence for a dose dependent action of external signals for several cell functions in parallel. This versatility of the effects of one ligand might be based on several intracellular signal transduction pathways that are turned on. For the dose-dependent differences of the effect of interleukin-8 we propose a two wheel model of an inositolphosphate-mediated, ATP-independent release of calcium from intracellular stores and a cyclic AMP-mediated, ATP-dependent uptake of calcium into the endoplasmatic reticulum.
Assuntos
Humanos , Fenômenos Fisiológicos Celulares/efeitos dos fármacos , Quimiotaxia de Leucócito/efeitos dos fármacos , Interleucina-8/farmacologia , Fator de Crescimento Epidérmico/farmacologia , Neutrófilos/efeitos dos fármacos , Neoplasias da Mama/patologia , Células Tumorais Cultivadas , Adenocarcinoma/patologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Quimiotaxia de Leucócito/fisiologia , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Microscopia de Vídeo , Citometria de Fluxo , Neutrófilos/fisiologiaRESUMO
We describe a woman in whom inhibitors to factor VIII:C developed in her first pregnancy. The neonate had a factor VIII:C level of 1% and an inhibitor titer of 5.2 Bethesda units. After an uneventful vaginal delivery, the boy had an intracranial hemorrhage at 5 days of age. To our knowledge, this is the first report of a bleeding complication in a newborn infant with transplacental transfer of an acquired factor VIII:C inhibitor.
Assuntos
Hemorragia Cerebral/fisiopatologia , Fator VIII , Hemofilia A/complicações , Recém-Nascido , Troca Materno-Fetal , Lobo Occipital/fisiopatologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico , Feminino , Hemofilia A/diagnóstico , Hemofilia A/tratamento farmacológico , Humanos , Masculino , Gravidez , Tomografia Computadorizada por Raios XRESUMO
A meningococcal group B (15:P1.3) outer membrane protein vaccine was tested for efficacy in a randomized, double-blind controlled study in Iquique, Chile. A total of 40 811 volunteers, ages 1-21 years, enrolled in the study. Volunteers received two doses of vaccine six weeks apart by jet injector. Both the experimental vaccine and the control vaccine (Menomune, A, C, Y and W135 meningococcal polysaccharide vaccine) were well tolerated with minor side-effects. Active surveillance for suspected cases of meningococcal disease was conducted for 20 months in Iquique. Eighteen cases of group B meningococcal disease were confirmed during the 20 months. Efficacy was estimated to be 51% (p = 0.11) for all ages combined. In children aged 1-4 no protection was evident, but in volunteers aged 5-21 vaccine efficacy was 70% (p = 0.045). The IgG antibody response by ELISA was characterized by a large booster effect after the second dose, followed by a substantial drop in antibody levels by 6 months. The youngest children had the highest responses. The bactericidal antibody response, on the other hand, was characterized by the lack of a significant booster response, higher responses in the older children, and an increase in the geometric mean titer in the later months of the study in the older children.
Assuntos
Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/imunologia , Meningite/imunologia , Neisseria meningitidis/imunologia , Porinas , Adolescente , Adulto , Anticorpos Antibacterianos/biossíntese , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/efeitos adversos , Western Blotting , Criança , Pré-Escolar , Chile , Proteínas do Sistema Complemento/metabolismo , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Masculino , Meningite/metabolismo , Meningite/prevenção & controle , Faringe/microbiologia , Estudos ProspectivosRESUMO
Hereditary predisposition to retinoblastoma is caused by germline mutations in the RB1 gene. Most of these mutations occur de novo and differ from one patient to another. DNA samples from 10 families with a child presenting sporadic bilateral retinoblastoma have been analysed for the causative mutation. Using intragenic DNA polymorphisms we detected large deletions in two patients. Heteroduplex and DNA sequence analysis of PCR products from each exon and the promoter region showed small mutations in four patients: a C to T transition in exon 18; 1 bp and 2 bp deletion in exons 20 and 19 respectively; and a 4 bp insertion in exon 7. All these mutations are likely to result in premature termination of transcription. In one of these families, an unaffected carrier was detected. This emphasises the importance of detection of the causative mutation for predictive diagnosis in families with sporadic bilateral retinoblastoma.
Assuntos
Genes do Retinoblastoma , Mutação em Linhagem Germinativa/genética , Retinoblastoma/genética , Argentina , Sequência de Bases , Southern Blotting , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Ácidos Nucleicos Heteroduplexes/química , Linhagem , Mutação Puntual/genética , Análise de Sequência de DNA , Deleção de SequênciaAssuntos
Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/uso terapêutico , Polissacarídeos Bacterianos/imunologia , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Formação de Anticorpos , Cápsulas Bacterianas , Vacinas Bacterianas/efeitos adversos , Vacinas Bacterianas/imunologia , Criança , Pré-Escolar , Chile , Seguimentos , Humanos , Lactente , Vacinas MeningocócicasRESUMO
The increasing use of brachytherapy in patients with cancer mandates that the informational needs of these patients are met. A nonrandomized sample of 22 patients undergoing brachytherapy participated in a study to determine (1) informational needs, (2) the degree to which patients prefer to be informed about and to participate in their medical care, and (3) the relationship between informational needs and selected variables. Most patients (86.4%) desired maximum information about their illness. The informational needs most frequently identified preimplant were how to manage side effects (54.5%), activity restrictions during implant (54.5%), pain management and comfort measures (54.5%), cause of current symptoms (54.5%), and how the implant could affect symptoms (54.5%). Postimplant needs included when to call the doctor (68%), possible side effects of treatment (64%), and how to manage side effects (63.6%). A significantly lower level of anxiety was found after the implant, compared to before the implant (p less than 0.005). A significant relationship was found between the number of informational needs and the stage of disease. Patients with advanced late disease (stages III and IV) had fewer informational needs than those with early disease (stages I and II), both before and after the implant (p less than 0.05). The results indicate that patients receiving brachytherapy have a variety of informational needs and generally prefer to be fully informed about their condition. The findings indicate possible content areas for educational programs and for counseling of patients undergoing brachytherapy.