RESUMO
Body-element content was measured for three life stages of wild Atlantic salmon Salmo salar from three distinct Newfoundland populations as individuals crossed between freshwater and marine ecosystems. Life stage explained most of the variation in observed body-element concentration whereas river of capture explained very little variation. Element composition of downstream migrating post-spawn adults (i.e. kelts) and juvenile smolts were similar and the composition of these two life stages strongly differed from adults migrating upstream to spawn. Low variation within life stages and across populations suggests that S. salar may exert rheostatic control of their body-element composition. Additionally, observed differences in trace element concentration between adults and other life stages were probably driven by the high carbon concentration in adults because abundant elements, such as carbon, can strongly influence the observed concentrations of less abundant elements. Thus, understanding variation among individuals in trace elements composition requires the measurement of more abundant elements. Changes in element concentration with ontogeny have important consequences the role of fishes in ecosystem nutrient cycling and should receive further attention.
Assuntos
Migração Animal , Ecossistema , Salmo salar/metabolismo , Animais , Tamanho Corporal , Terra Nova e Labrador , Rios , Salmo salar/crescimento & desenvolvimentoRESUMO
BACKGROUND: There are very sparse data on the outcomes of children receiving prolonged extracorporeal membrane oxygenation (ECMO) after cardiac surgery. This study was aimed to evaluate the association of ECMO duration with outcomes in children undergoing surgery for congenital heart disease using the Pediatric Health Information System (PHIS) database. METHODS: Patients aged ≤18 years receiving ECMO after pediatric cardiac surgery (with or without cardiopulmonary bypass) at a PHIS-participating hospital (2004-2013) were included. De-identified data obtained from retrospective, observational dataset included demographic information, baseline characteristics, pre-ECMO risk factors, operation details, patient diagnoses, and center data. Outcomes evaluated included in-hospital mortality, length of mechanical ventilation, length of ICU stay, length of hospital stay, and hospital charges. Cox proportional hazards models were fitted to study the probability of study outcomes as a function of ECMO duration. RESULTS: Nine hundred ninety-eight patients from 37 hospitals qualified for inclusion. The median duration of ECMO run was 4 days (IQR: 1.7). After adjusting for patient and center characteristics, there was 12% increase in the odds of mortality for every 24 hours increase in ECMO duration (OR: 1.12, 95% CI: 1.07-1.18, P<0.001). Patients receiving longer duration of ECMO were associated with longer length of mechanical ventilation, longer length of ICU stay, longer length of hospital stay, and higher hospital charges. CONCLUSION: Data from this large multicenter database suggest that longer duration of ECMO support after pediatric cardiac surgery is associated with worsening outcomes.
Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Adolescente , Procedimentos Cirúrgicos Cardíacos/mortalidade , Criança , Pré-Escolar , Oxigenação por Membrana Extracorpórea/métodos , Feminino , Mortalidade Hospitalar , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Masculino , Respiração Artificial , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Atlantic salmon Salmo salar smolts (n = 181) from two rivers were surgically implanted with acoustic transmitters and released to determine migration route, residency time and survival in a 50 km long estuarine fjord located on the south coast of Newfoundland, Canada. Data obtained from automated receivers placed throughout the Bay d'Espoir fjord indicated that migrating smolts used different routes to reach the outer areas of the fjord. The duration of time that smolts spent in the immediate estuary zone also differed between the two localities (7 and 17 days) although the total time smolts were resident in the fjord was similar and extensive (40 days). Many smolts were resident for periods of 4-8 weeks moving back and forth in the outer part of the fjord where maximum water depths range from 300 to 700 m. Survival in the estuary zone was greater for smolts with prolonged residency in estuarine habitat. Overall smolt survival to the fjord exit was moderately high (54-85%), indicating that the initial phase of migration did not coincide with a period of unusually high mortality.
Assuntos
Migração Animal , Salmo salar/fisiologia , Animais , Ecossistema , Água Doce , Terra Nova e Labrador , Rios , Salmo salar/crescimento & desenvolvimento , Água do Mar , Fatores de TempoRESUMO
We conducted a phase I trial to determine the maximum tolerated dose (MTD) of clofarabine with high-dose busulfan followed by allogeneic stem cell transplantation (SCT) in patients with high-risk and refractory acute leukemia. Patients received intravenous busulfan 0.8 mg/kg every 6 h on days -6 to -3 and clofarabine 30-60 mg/m(2) per day on days -6 to -2. Graft-versus-host disease prophylaxis included sirolimus plus tacrolimus (days -2 to +180). A total of 15 patients, median age 48 (30-58) years, with acute leukemia that was relapsed and refractory (n=8), primary refractory (n=6), or in CR2 (n=1), were treated at four clofarabine dose levels: 30 (n=3), 40 (n=3), 50 (n=3) and 60 mg/m(2) per day (n=6) with busulfan. All engrafted, and the MTD was not reached. Grades 3-4 non-hematological toxicities included vomiting (n=3), mucositis (n=9), hand-foot syndrome (n=1), acute renal failure (n=1) and reversible elevation of aspartate aminotransferase/alanine aminotransferase (n=10). The 1-year event-free survival was 53% (95% confidence interval: 33-86%), and the 1-year overall survival was 60% (95% confidence interval: 40-91%). Given the good tolerability and promising results, we recommend clofarabine 60 mg/m(2) per day × 5 days as a phase II dose in combination with busulfan (12.8 mg per kg total dose) for further study as a myeloablative regimen for allogeneic SCT for high-risk acute leukemia.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Transplante de Células-Tronco , Nucleotídeos de Adenina/administração & dosagem , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Arabinonucleosídeos/administração & dosagem , Bussulfano/administração & dosagem , Clofarabina , Terapia Combinada , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Fatores de Risco , Taxa de Sobrevida , Distribuição Tecidual , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Interleukin-18 (IL-18) is an immunostimulatory cytokine belonging to the IL-1 family. IL-18 can regulate both innate and adaptive immune responses through its effects on natural killer (NK) cells, monocytes, dendritic cells, T cells, and B cells. IL-18 acts synergistically with other pro-inflammatory cytokines to promote interferon-γ (IFN-γ) production by NK cells, T cells, and possibly other cell types. Systemic administration of IL-18 has been shown to have significant antitumor activity in several preclinical animal models. Phase I clinical trials of recombinant human IL-18 have demonstrated that it can be safely administered to patients with advanced cancer. Biologic effects of IL-18 therapy include activation of monocytes, NK cells, and T cells and production of IFN-γ as well as other cytokines in vivo. A phase II study of IL-18 in patients with metastatic melanoma confirmed its safety but suggested limited efficacy of IL-18 monotherapy in this setting. IL-18 appears to act predominantly as a costimulatory cytokine and its optimal use for cancer immunotherapy may be in combination with other immunostimulatory cytokines, vaccines, or monoclonal antibodies.
Assuntos
Antineoplásicos/uso terapêutico , Interleucina-18/uso terapêutico , Neoplasias/tratamento farmacológico , Ensaios Clínicos como Assunto , Terapia Combinada , Transplante de Células-Tronco Hematopoéticas , Humanos , Interleucina-18/metabolismo , Interleucina-18/fisiologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Neoplasias/metabolismo , Neoplasias/terapia , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
A total of 50 consecutive patients (median age, 57.5 years) with AML (n=30) or myelodysplasia (MDS, n=20) underwent HLA matched related donor (MRD, n=27) or unrelated donor (MUD, n=23) peripheral blood hematopoietic cell transplantation after nonmyeloablative CY/fludarabine (Flu) conditioning. GVHD prophylaxis included CsA (n=19)+/-mycophenolate mofetil (n=31). At a median follow-up of 59 months, 21 patients (42%) were alive without evidence of disease. By Kaplan-Meier analysis, year 1-4 disease-free survival (DFS) and OS estimates were 0.50/0.58, 0.40/0.46, 0.37/0.43 and 0.37/0.41. MUD recipients were engrafted quickly (13.5 days) compared to MRD recipients (16 days) and relapsed/progressed less frequently (P=0.005). Overall grade 3/4 acute GVHD (aGVHD) occurred in 26% in the absence of antecedent mucositis and was associated with chronic GVHD (cGVHD) and poor OS. Extensive cGVHD developed in 51.2% of 100 day survivors. Rates of aGVHD, cGVHD and survival were similar between MRD and MUD recipients. Of 14 survivors with cGVHD, 5 (35.7%) experienced resolution off immunosuppression, suggesting that tolerance with HLA matched grafts is possible at an advanced age by this method. This study provides further evidence for prolonged DFS after CY/Flu MRD allotransplantation for AML/MDS, and extends the findings to older patients and those with unrelated donors.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Transplante Homólogo , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Adulto JovemRESUMO
Community and catchment-based approaches to salinity management continue to attract interest in Australia. In one such approach, Catchment Demonstration Initiative (CDI) projects were established by the Western Australian (WA) Government in 2000 for targeted investment in large-scale catchment-based demonstrations of integrated salinity management practices. The aim was to promote a process for technically-informed salinity management by landholders. This paper offers an evaluation of the effectiveness of one CDI project in the central wheatbelt of WA, covering issues including: its role in fostering adoption of salinity management options, the role of research and the technical requirements for design and implementation of on-ground works, the role of monitoring and evaluation, the identification and measurement of public and private benefits, comparison and identification of the place and value of plant-based and engineering-based options, reliance on social processes and impacts of constraints on capacity, management of governance and administration requirements and an appreciation of the value of group-based approaches. A number of factors may reduce the effectiveness of CDI-type approaches in facilitating landholder action to address salinity, many of these are socially-based. Such approaches can create considerable demands on landholders, can be expensive (because of the planning and accountability required) on the basis of dollars per hectare impacted, and can be difficult to garner ownership from all involved. An additional problem could be that few community groups would have the capacity to run such programs and disseminate the new knowledge so that the CDI-type projects can impact outside the focus catchment. In common with many publicly-funded approaches to salinity, we found that direct benefits on public assets are smaller than planned and that results from science-based requirements of monitoring and evaluation have long lead times, causing farmers to either wait for the information or act sooner and take risks based on initial results. We also found that often it is a clear outline of the process that is of most importance in decision making as opposed to the actual results. We identified limitations in regulatory processes and the capacity for local government to engage in the CDI. The opportunities that CDI-type approaches provide centre around the value of its group-based approach. We conclude that they can overcome knowledge constraints in managing salinity by fostering group-based learning, offer a structured process of trialling options so that the costs and benefits can be clearly and transparently quantified, and avoid the costly mistakes and "learning failures" of the past.
Assuntos
Monitoramento Ambiental/métodos , Salinidade , Austrália , Monitoramento Ambiental/economia , Desenvolvimento de Programas/economia , Avaliação de Programas e Projetos de Saúde/economiaRESUMO
BACKGROUND: We previously reported results of the phase 2, multicenter PINNACLE study, which confirmed the substantial single-agent activity of bortezomib in patients with relapsed or refractory mantle cell lymphoma (MCL). MATERIALS AND METHODS: We report updated time-to-event data, in all patients and by response to treatment, after extended follow-up (median 26.4 months). RESULTS: Median time to progression (TTP) was 6.7 months. Median time to next therapy (TTNT) was 7.4 months. Median overall survival (OS) was 23.5 months. In responding patients, median TTP was 12.4 months, median duration of response (DOR) was 9.2 months, median TTNT was 14.3 months, and median OS was 35.4 months. Patients achieving complete response had heterogeneous disease characteristics; among these patients, median TTP and DOR were not reached, and median OS was 36.0 months. One-year survival rate was 69% overall and 91% in responding patients. Median OS from diagnosis was 61.1 months, after median follow-up of 63.7 months. Activity was seen in patients with refractory disease and patients relapsing following high-intensity treatment. Toxicity was generally manageable. CONCLUSIONS: Single-agent bortezomib is associated with lengthy responses and notable survival in patients with relapsed or refractory MCL, with considerable TTP and TTNT in responding patients, suggesting substantial clinical benefit.
Assuntos
Antineoplásicos/uso terapêutico , Ácidos Borônicos/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Pirazinas/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Ácidos Borônicos/efeitos adversos , Bortezomib , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pirazinas/efeitos adversos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Autologous hematopoietic cell transplantation (HCT) is being used to treat autoimmune diseases refractory to conventional therapy, including rheumatoid arthritis. Macrophage activation syndrome (MAS) is a descriptive term for a systemic inflammatory disorder that has been described in patients with juvenile rheumatoid arthritis (JRA). This case report describes a young adult with systemic JRA (sJRA) who developed MAS on day # 12 post-autologous transplantation. The patient developed high fever, laboratory evidence of disseminated intravascular coagulation (DIC), hepatocellular injury, pancytopenia and hyper-ferritinemia. All viral, bacterial and fungal studies were negative and the patient improved with high-dose glucocorticosteroid and cyclosporine therapy. Extreme elevation of serum ferritin was documented and helpful in monitoring response to therapy. A number of systemic inflammatory syndromes have been described in association with HCT. These include DIC, 'engraftment syndrome,' infection-associated hemophagocytic syndrome and familial hemophagocytic lymphohistiocytosis. Macrophage activation syndrome presents with features of DIC and is closely related or identical to infection-associated hemophagocytic syndrome. The diagnosis needs to be established in a timely fashion because early and appropriate treatment may improve outcome.
Assuntos
Doenças Autoimunes/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Adulto , Artrite Juvenil/diagnóstico , Artrite Juvenil/imunologia , Artrite Juvenil/terapia , Doenças Autoimunes/etiologia , Doenças Autoimunes/terapia , Humanos , Inflamação/imunologia , Masculino , Indução de Remissão , SíndromeRESUMO
Chronic fatigue syndrome (CFS) is a heterogeneous disorder of unknown aetiology characterized by debilitating fatigue, along with other symptoms, for at least 6 months. Many studies demonstrate probable involvement of the central and autonomic nervous system, as well as a state of generalized immune activation and selective immune dysfunction in patients with CFS. The aim of this study was to compare the lymphocyte subsets of patients with chronic fatigue syndrome to those of patients with major depression and multiple sclerosis as well as those of healthy control subjects. No differences were found in total numbers of T cells, B cells or natural killer (NK) cells. However, differences were found in T, B and NK cell subsets. Patients with major depression had significantly fewer resting T (CD3(+)/CD25(-)) cells than the other groups. Patients with major depression also had significantly more CD20(+)/CD5(+) B cells, a subset associated with the production of autoantibodies. Compared to patients with multiple sclerosis, patients with CFS had greater numbers of CD16(+)/CD3(-) NK cells. Further study will be required to determine whether these alterations in lymphocyte subsets are directly involved in the pathophysiology of these disorders, or are secondary effects of the causal agent(s).
Assuntos
Transtorno Depressivo Maior/imunologia , Síndrome de Fadiga Crônica/imunologia , Subpopulações de Linfócitos/imunologia , Esclerose Múltipla/imunologia , Adulto , Subpopulações de Linfócitos B/imunologia , Feminino , Humanos , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Masculino , Subpopulações de Linfócitos T/imunologiaRESUMO
SETTING: Community-based population of homeless adults living in San Francisco, California. OBJECTIVE: To compare the effect of cash and non-cash incentives on 1) adherence to treatment for latent tuberculosis infection, and 2) length of time needed to look for participants who missed their dose of medications. DESIGN: Prospective, randomized clinical trial comparing a 5 dollar cash or a 5 dollar non-cash incentive. All participants received directly observed preventive therapy and standardized follow-up per a predetermined protocol. Completion rates and amount of time needed to follow up participants was measured. RESULTS: Of the 119 participants, 102 (86%) completed therapy. There was no difference between the cash and non-cash arms. Completion was significantly higher among males (OR 5.65, 95%CI 1.36-23.40, P = 0.02) and persons in stable housing at study entry (OR 4.86, 95%CI 1.32-17.94, P = 0.02). No substance use or mental health measures were associated with completion. Participants in the cash arm needed significantly less follow-up to complete therapy compared to the non-cash arm (P = 0.03). In multivariate analysis, non-cash incentive, use of crack cocaine, and no prior preventive therapy were associated with more follow-up time. CONCLUSION: Simple, low cost incentives can be used to improve adherence to TB preventive therapy in indigent adults.
Assuntos
Antituberculosos/administração & dosagem , Pessoas Mal Alojadas/estatística & dados numéricos , Motivação , Cooperação do Paciente/estatística & dados numéricos , Tuberculose/tratamento farmacológico , Adulto , California , Intervalos de Confiança , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Seleção de Pacientes , Pobreza , Probabilidade , Estudos Prospectivos , Valores de Referência , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Tuberculose/diagnóstico , População UrbanaRESUMO
A novel secreted cytokine, termed IL-17F, was cloned using nested RACE PCR. This cytokine bears homology to IL-17. IL-17F was expressed only in activated CD4(+) T cells and activated monocytes. Recombinant human IL-17F did not stimulate the proliferation of hematopoietic progenitors or the migration of mature leukocytes. However, it markedly inhibited the angiogenesis of human endothelial cells and induced endothelial cells to produce IL-2, TGF-beta, and monocyte chemoattractant protein-1.
Assuntos
Inibidores da Angiogênese/farmacologia , Endotélio Vascular/efeitos dos fármacos , Interleucina-17/farmacologia , Monócitos/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Linfócitos T/metabolismo , Sequência de Aminoácidos , Inibidores da Angiogênese/biossíntese , Inibidores da Angiogênese/genética , Sequência de Bases , Clonagem Molecular , Citocinas/biossíntese , Humanos , Interleucina-17/genética , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Proteínas Recombinantes/biossíntese , Homologia de Sequência de AminoácidosAssuntos
Infecções por Vírus Epstein-Barr/terapia , Células Matadoras Naturais/imunologia , Transtornos Linfoproliferativos/terapia , Animais , Modelos Animais de Doenças , Infecções por Vírus Epstein-Barr/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Imunoterapia , Interleucina-2/uso terapêutico , Transtornos Linfoproliferativos/imunologia , Camundongos , Camundongos SCIDRESUMO
Findings are presented for a cross-sectional study of serological markers of hepatitis B virus (HBV) infection in an underserved population-impoverished veterans of the US armed forces in a Veterans Administration (VA) residential program in the US. We examine the demographic, background, and risk factors associated with HBV infection in this high-risk population. This paper presents a secondary analysis of cross-sectional survey and clinical data for 370 male veterans who were residents of a domiciliary care program for homeless veterans in Los Angeles, using chi(2), Fisher's Exact, and logistic regression analysis. About one-third (30.8%) of the sample tested positive for current or past HBV infection (ie, seropositive for either the HBV core antibody or surface antigen). After multivariate analysis, rates of HBV were significantly higher among veterans who were older, non-white, or who had a history of regular heroin use (a proxy measure for injection drug use), drug overdose, or drug detoxification treatment. The rate of current or past HBV infection among veterans in this sample (30.8%) was high compared to an estimated 5% to 8% of the general US population. Also, 3% of the sample were currently infected with HBV. Strategies for intervention include broader screening, immunization, and treatment interventions with this high-risk group.
Assuntos
Hepatite B/epidemiologia , Pessoas Mal Alojadas/estatística & dados numéricos , Instituições Residenciais , Veteranos/estatística & dados numéricos , Adulto , Estudos Transversais , Humanos , Los Angeles/epidemiologia , Masculino , Pessoa de Meia-IdadeRESUMO
Pre-clinical studies indicate that efficient retrovirus-mediated gene transfer into hematopoietic stem cells and progenitor cells can be achieved by co-localizing retroviral particles and target cells on specific adhesion domains of fibronectin. In this pilot study, we used this technique to transfer the human multidrug resistance 1 gene into stem and progenitor cells of patients with germ cell tumors undergoing autologous transplantation. There was efficient gene transfer into stem and progenitor cells in the presence of recombinant fibronectin fragment CH-296. The infusion of these cells was associated with no harmful effects and led to prompt hematopoietic recovery. There was in vivo vector expression, but it may have been limited by the high rate of aberrant splicing of the multidrug resistance 1 gene in the vector. Gene marking has persisted more than a year at levels higher than previously reported in humans.
Assuntos
Fibronectinas/genética , Técnicas de Transferência de Genes , Genes MDR , Vetores Genéticos , Germinoma/terapia , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Retroviridae , Adolescente , Adulto , Antígenos CD34 , Seguimentos , Terapia Genética/métodos , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Tempo , Resultado do TratamentoRESUMO
Natural killer (NK) cells play an important role in innate and adaptive immune responses to obligate intracellular pathogens. Nevertheless, the regulation of NK cell trafficking and migration to inflammatory sites is poorly understood. Exodus-1/MIP-3alpha/LARC, Exodus-2/6Ckine/SLC, and Exodus-3/MIP-3beta/ELC/CKbeta-11 are CC chemokines that share a unique aspartate-cysteine-cysteine-leucine motif near their amino terminus and preferentially stimulate the migration of T lymphocytes. The effects of Exodus chemokines on human NK cells were examined. Exodus-1, -2, and -3 did not induce detectable chemotaxis of resting peripheral blood NK cells. In contrast, Exodus-2 and -3 stimulated migration of polyclonal activated peripheral blood NK cells in a dose-dependent fashion. Exodus-2 and -3 also induced dose-dependent chemotaxis of NKL, an IL-2-dependent human NK cell line. Results of modified checkerboard assays indicate that migration of NKL cells in response to Exodus-2 and -3 represents true chemotaxis and not simply chemokinesis. Exodus-1, -2, and -3 did not induce NK cell proliferation in the absence of other stimuli. Nevertheless, Exodus-2 and -3 significantly augmented IL-2-induced proliferation of normal human CD56(dim) NK cells. In contrast, Exodus-1, -2, and -3 did not affect the cytolytic activity of resting or activated peripheral blood NK cells. Expression of message for CCR7, a shared receptor for Exodus-2 and -3, was detected in activated polyclonal NK cells and NKL cells but not resting NK cells. Taken together, these results indicate that Exodus-2 and -3 can participate in the recruitment and proliferation of activated NK cells. Exodus-2 and -3 may regulate interactions between T cells and NK cells that are crucial for the generation of optimal immune responses.
Assuntos
Quimiocinas CC/farmacologia , Quimiotaxia de Leucócito/efeitos dos fármacos , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Proteínas Inflamatórias de Macrófagos , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Quimiocina CCL19 , Quimiocina CCL20 , Quimiocina CCL21 , Quimiotaxia de Leucócito/imunologia , Técnicas de Cocultura , Citotoxicidade Imunológica/efeitos dos fármacos , Citotoxicidade Imunológica/imunologia , Relação Dose-Resposta Imunológica , Expressão Gênica , Humanos , Interleucina-2/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Ativação Linfocitária , RNA Mensageiro/análise , RNA Mensageiro/genética , Receptores CCR6 , Receptores CCR7 , Receptores de Quimiocinas/genéticaRESUMO
1. In the present study we have investigated the roles of P2Y(1) and P(2T) receptor subtypes in adenosine 5'-diphosphate (ADP)-induced aggregation of human platelets in heparinized platelet rich plasma. 2. The response to ADP can be characterized as the initial rate or the maximum or final extent of aggregation. The response profile is determined by the concentration of ADP used, being transient at lower and sustained at higher concentrations. 3. The P2Y(1) receptor antagonist, adenosine-3'-phosphate-5'-phosphate (A3P5P) competitively antagonized the initial rate of aggregation (pK(B) 5. 47) and transformed the response profile to a slowly developing but sustained response. Both maximum and final extents were also inhibited by A3P5P although not in a competitive manner (Schild slope <1). 4. The P(2T) receptor antagonist, AR-C67085, competitively antagonized the final extent of aggregation (pK(B) 8.54), transforming the response profile to one of rapid, transient aggregation. Its effect on maximum extent (the most widely used index of aggregation) was complex, and further supported the involvement of both receptor subtypes in the aggregation response. 5. ADP-induced aggregation is a complex phenomenon, the nature of which is determined by the relative occupancy of the two receptor subtypes. While P2Y(1) receptor activation causes a rapid and transient aggregation, the extent of sustained aggregation is determined by the level of P(2T) receptor occupancy. Hence, detailed analysis of the aggregation response is essential to correctly define the purinergic pharmacology of the platelet and interpretation of results is critically dependent on the response index chosen.
Assuntos
Difosfato de Adenosina/farmacologia , Proteínas de Membrana , Agregação Plaquetária/efeitos dos fármacos , Receptores Purinérgicos P2/efeitos dos fármacos , Difosfato de Adenosina/análogos & derivados , Difosfato de Adenosina/antagonistas & inibidores , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Adulto , Algoritmos , Ligação Competitiva/efeitos dos fármacos , Feminino , Humanos , Técnicas In Vitro , Masculino , Inibidores da Agregação Plaquetária/farmacologia , Receptores Purinérgicos P2Y1 , Receptores Purinérgicos P2Y12 , Tromboxano A2/metabolismoRESUMO
The performance of selected, commercially available InGaAs/InP avalanche photodiodes operating in a photon-counting mode at an incident wavelength of 1.55 microm is described. A discussion on the optimum operating conditions and their relationship to the electric field distribution within the device is presented.
RESUMO
The concurrent validity of interview-based ratings of negative symptoms in 35 inpatients with chronic, treatment refractory schizophrenia was evaluated. Correlations were examined between interview-based ratings of negative symptoms, measured by the Brief Psychiatric Rating Scale and the Positive and Negative Syndrome Scale, and the naturalistic behavior of inpatients as assessed by the Time Sample Behavior Checklist. Higher levels of interview-based negative symptoms were related to reduced interpersonal activity on the inpatient ward, but not to entertainment, instrumental or self-maintenance activities. These findings offer partial support for the concurrent validity of office-based ratings of negative symptoms, and highlight the importance of longitudinal observations of patients for accurate identification of negative symptoms.