RESUMO
Malperfusion syndrome is considered one of the most significant adverse events in aortic dissection disease and often requires invasive strategies to improve ischemia. We report the case of a patient who was presented with worsening claudication and leg rest pain due to malperfusion syndrome of type B aortic dissection. We successfully performed endovascular fenestration therapy to relieve the symptom by using a NRG radiofrequency transseptal needle (Baylis Medical, Montreal, Canada). We suggest that this novel method would be available for the patients with malperfusion syndrome of aortic dissection.
RESUMO
The accumulation of intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) is associated with arterial stiffness in middle-aged and older adults. Habitual aerobic exercise induces the improvement of arterial stiffness with reduction in fat accumulation. However, the relationship between aerobic exercise-induced changes in muscular lipids and arterial stiffness remains unclear. The purpose of this study was to investigate whether habitual aerobic exercise-induced changes in IMCL and EMCL content would lead to an improvement of arterial stiffness. First, in a cross-sectional study, we investigated whether cardiorespiratory fitness level affects the association between IMCL or EMCL content and arterial stiffness in 60 middle-aged and older subjects (61.0±1.3 years). Second, in an intervention study, we examined whether aerobic exercise training-induced changes in IMCL and EMCL content are associated with a reduction in arterial stiffness in 18 middle-aged and older subjects (67.0±1.7 years). In the cross-sectional study, IMCL content was negatively correlated with brachial-ankle pulse wave velocity (baPWV) (r=-0.47, P<0.05), whereas EMCL content was positively correlated with baPWV (r=0.48, P<0.05) in the low-fitness group, but was not correlated in the high-fitness group. Furthermore, 8-week aerobic exercise training in older adults increased IMCL content and reduced EMCL content. The training-induced change in baPWV was negatively correlated with training-induced changes in IMCL but was positively correlated with training-induced changes in EMCL. These findings suggest that aerobic exercise training-induced changes in IMCL and EMCL content may be related to a reduction in arterial stiffness in middle-aged and older adults.
Assuntos
Exercício Físico/fisiologia , Metabolismo dos Lipídeos , Células Musculares/metabolismo , Rigidez Vascular , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Ischemic preconditioning (IPC) enhances whole-body exercise endurance. However, it is poorly understood whether the beneficial effects originate from systemic (e. g., cardiovascular system) or peripheral (e. g., skeletal muscle) adaptations. The present study examined the effects of IPC on local muscle endurance during fatiguing isometric exercise. 12 male subjects performed sustained isometric unilateral knee-extension exercise at 20% of maximal voluntary contraction until failure. Prior to the exercise, subjects completed IPC or control (CON) treatments. During exercise trial, electromyography activity and near-infrared spectroscopy-derived deoxygenation in skeletal muscle were continuously recorded. Endurance time to task failure was significantly longer in IPC than in CON (mean±SE; 233±9 vs. 198±9 s, P<0.001). Quadriceps electromyography activity was not significantly different between IPC and CON. In contrast, deoxygenation dynamics in the quadriceps vastus lateralis muscle was significantly faster in IPC than in CON (27.1±3.4 vs. 35.0±3.6 s, P<0.01). The present study found that IPC can enhance muscular endurance during fatiguing isometric exercise. Moreover, IPC accelerated muscle deoxygenation dynamics during the exercise. Therefore, we suggest that the origin of beneficial effects of IPC on exercise performance may be the enhanced mitochondrial metabolism in skeletal muscle.
Assuntos
Exercício Físico/fisiologia , Precondicionamento Isquêmico , Resistência Física/fisiologia , Músculo Quadríceps/fisiologia , Eletromiografia , Humanos , Contração Isométrica , Joelho , Masculino , Fadiga Muscular/fisiologia , Oxigênio/fisiologia , Consumo de Oxigênio , Adulto JovemRESUMO
Regular exercise improves aging-induced deterioration of arterial stiffness, and is associated with elevated production of pentraxin 3 (PTX3) and anti-inflammatory as well as anti-atherosclerotic effects. However, the time-dependent effect of exercise training on arterial stiffness and PTX3 production remains unclear. The purpose of this study was to investigate the time course of the association between the effects of training on the circulating PTX3 level and arterial stiffness in middle-aged and older adults. Thirty-two healthy Japanese subjects (66.2±1.3 year) were randomly divided into two groups: training (exercise intervention) and sedentary controls. Subjects in the training group completed 8 weeks of aerobic exercise training (60-70% peak oxygen uptake (VO2peak) for 45 min, 3 days per week); during the training period, we evaluated plasma PTX3 concentration and carotid-femoral pulse wave velocity (cfPWV) every 2 wk. cfPWV gradually declined over the 8-week training period, and was significantly reduced after 6 and 8 week of exercise intervention (P<0.05). Plasma PTX3 level was significantly increased after 4 weeks of the intervention (P<0.05). In addition, the exercise training-induced reduction in cfPWV was negatively correlated with the percent change in plasma PTX3 level after 6 week (r=-0.54, P<0.05) and 8 weeks (r=-0.51, P<0.05) of the intervention, but not correlated at 4 weeks. Plasma PTX3 level was elevated at the early stage of the exercise training intervention, and was subsequently associated with training-induced alteration of arterial stiffness in middle-aged and older adults.
Assuntos
Envelhecimento/sangue , Proteína C-Reativa/metabolismo , Exercício Físico , Componente Amiloide P Sérico/metabolismo , Rigidez Vascular , Fatores Etários , Idoso , Biomarcadores/sangue , Feminino , Humanos , Japão , Masculino , Análise de Onda de Pulso , Comportamento Sedentário , Fatores de Tempo , Regulação para CimaRESUMO
We investigated the effect of a training program consisting of planned overreaching and subsequent short-term detraining on sprint performance. 24 physically active men participated in an 18-day sprint-training program. They were divided into 2 groups: the overreaching-detraining (OR-DT) and the control (CON) groups. Subjects in the OR-DT group performed 12 consecutive days of maximal cycle sprint training followed by 6 days of detraining, whereas a rest day was provided after every 2 successive training days for the CON group. Peak power output during maximal pedaling increased significantly after 6 days of detraining in the OR-DT group compared with the baseline (P<0.05), whereas no change was observed in CON group. Intramuscular phosphocreatine concentration increased significantly after 12 days of daily training in the OR-DT group (69.3±45.8% increase vs. baseline, P<0.05), and it was maintained after the detraining period (46.6±33.6% increase vs. baseline, P<0.05). However, no change was observed in CON group. No significant changes in blood variables were observed after the training period except significant reduction of serum cortisol in the CON group. Daily sprint training and subsequent short-term detraining enhanced peak power output after the detraining period.
Assuntos
Desempenho Atlético/fisiologia , Ciclismo/fisiologia , Adaptação Fisiológica/fisiologia , Adulto , Limiar Anaeróbio/fisiologia , Biomarcadores/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Consumo de Oxigênio/fisiologia , Fosfocreatina/metabolismo , Descanso/fisiologiaRESUMO
AIM: To examine the blood flow (BF) response in the lower abdomen (LAB) in recovery following upright cycling exercise at three levels of relative maximum pulmonary oxygen consumption (VO(2max)) and the relationship of BF(LAB) to heart rate (HR) and target intensity. METHODS: For 11 healthy subjects, BF (Doppler ultrasound) in the upper abdominal aorta (Ao) above the coeliac trunk and in the right femoral artery (RFA) was measured repeatedly for 720 s after the end of cycling exercises at target intensities of 30%, 50% and 85% VO(2max), respectively. Blood flow in the lower abdomen (BF(LAB)) can be measured by subtracting bilateral BF(FAs) (≈twofolds of BF(RFA)) from BF(Ao). Change in BF(LAB) (or BF(LAB) volume) at any point was evaluated by difference between change in BF(Ao) and in BF(FAs). Heart rate and blood pressure were also measured. RESULTS: At 85% VO(2max), significant reduction in BF(LAB) by approx. 89% was shown at 90 s and remained until 360 s. At 50% VO(2max), reduction in BF(LAB) by approx. 33% was found at 90 s although it returned to pre-exercise value at 120 s. On the contrary at 30% VO(2max), BF(LAB) showed a light increase (<20%) below 70 bpm of HR. There was a close negative relationship (P < 0.05) between change in BF(LAB) and recovery HR, as well as between change in BF(LAB) volume and both recovery HR and % VO(2max). CONCLUSION: This study suggests that the lower abdominal BF in recovery may be influenced by sympathetic-vagus control, and dynamics of BF(LAB) may be closely related to the level of relative exercise intensities.
Assuntos
Abdome/irrigação sanguínea , Aorta Abdominal/fisiologia , Ciclismo , Exercício Físico , Artéria Femoral/fisiologia , Frequência Cardíaca , Circulação Esplâncnica , Adulto , Análise de Variância , Aorta Abdominal/diagnóstico por imagem , Pressão Sanguínea , Artéria Femoral/diagnóstico por imagem , Humanos , Modelos Lineares , Masculino , Contração Muscular , Consumo de Oxigênio , Ventilação Pulmonar , Recuperação de Função Fisiológica , Fluxo Sanguíneo Regional , Fatores de Tempo , Ultrassonografia Doppler , Adulto JovemRESUMO
BACKGROUND: We compared the utility of a new response classification (MDA; based on computed tomography (CT), magnetic resonance imaging (MRI), plain radiography (XR), and skeletal scintigraphy (SS)) and the World Health Organisation response classification (WHO; based on XR and SS) in stratifying breast cancer patients with bone-only metastases with respect to progression-free survival (PFS), overall survival (OS), and clinical response. METHODS: We retrospectively reviewed 41 patients with bone-only metastatic breast cancer and assigned responses according to the MDA and WHO criteria. We analysed whether the MDA or WHO response classifications correlated with PFS and OS. RESULTS: With the MDA criteria, there were significant differences in PFS between patients classified as responders and those classified as nonresponders (P=0.025), but with the WHO criteria, there were not. Neither criteria distinguished responders from nonresponders in terms of OS. MDA response criteria correlated better than WHO response criteria with clinical response assessment. CONCLUSIONS: The MDA classification is superior to the WHO classification in differentiating between responders and nonresponders among breast cancer patients with bone-only metastases. Application of the MDA classification may allow bone lesions to be considered measurable disease. Prospective study is needed to test the MDA classification among patients with bone metastasis.
Assuntos
Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Carcinoma/patologia , Estadiamento de Neoplasias/métodos , Organização Mundial da Saúde , Adulto , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Carcinoma/diagnóstico por imagem , Carcinoma/secundário , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
AIM: To examine the effects of low-volume muscle endurance training on muscle oxidative capacity, endurance and strength of the forearm muscle during 21-day forearm immobilization (IMM-21d). METHODS: The non-dominant arm (n = 15) was immobilized for 21 days with a cast and assigned to an immobilization-only group (Imm-group; n = 7) or an immobilization with training group (Imm+Tr-group; n = 8). Training comprised dynamic handgrip exercise at 30% of pre-intervention maximal voluntary contraction (MVC) at 1 Hz until exhaustion, twice a week during the immobilization period. The duration of each exercise session was 51.7 +/- 3.4 s (mean +/- SE). Muscle oxidative capacity was evaluated by the time constant for phosphocreatine recovery (tau(off)PCr) after a submaximal handgrip exercise using (31)phosphorus-magnetic resonance spectroscopy. An endurance test was performed at 30% of pre-intervention MVC, at 1 Hz, until exhaustion. RESULTS: tau(off)PCr was significantly prolonged in the Imm-group after 21 days (42.0 +/- 2.8 and 64.2 +/- 5.1 s, pre- and post-intervention respectively; P < 0.01) but did not change for the Imm+Tr-group (50.3 +/- 3.0 and 48.8 +/- 5.0 s, ns). Endurance decreased significantly for the Imm-group (55.1 +/- 5.1 and 44.7 +/- 4.6 s, P < 0.05) but did not change for the Imm+Tr-group (47.9 +/- 3.0 and 51.7 +/- 4.0 s, ns). MVC decreased similarly in both groups (P < 0.01). CONCLUSIONS: Twice-weekly muscle endurance training sessions, each lasting approx. 50 s, effectively prevented a decrease in muscle oxidative capacity and endurance; however, there was no effect on MVC decline with IMM-21d.
Assuntos
Exercício Físico/fisiologia , Antebraço , Imobilização/fisiologia , Contração Muscular/fisiologia , Músculo Esquelético/metabolismo , Consumo de Oxigênio/fisiologia , Resistência Física/fisiologia , Adulto , Teste de Esforço , Antebraço/anatomia & histologia , Antebraço/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Força Muscular/fisiologia , Fatores de Tempo , Adulto JovemRESUMO
The Wilms' tumor gene WT1 is highly expressed in leukemias and myelodysplastic syndrome (MDS), and WT1 expression levels increase along with the disease progression in chronic myeloid leukemia and MDS. We previously reported that IgM and IgG WT1 antibodies were detected with significantly higher detection rate and antibody titers in leukemias and MDS compared to those in healthy volunteers. In this study, whether IgG humoral immune responses against WT1 protein were Th1- or Th2-type were determined by measurement of four subclasses of IgG WT1 antibody, IgG1, IgG2, IgG3, and IgG4. In leukemias and MDS, Th1-type WT1 antibodies such as IgG1, IgG2, and IgG3 were significantly increased in both detection rate and antibody titers compared to those in healthy volunteers, whereas Th2-type WT1 antibody such as IgG4 did not increase. These results showed that Th1-biased humoral immune responses against WT1 protein were generated in leukemias and MDS. These results should allow us to consider that Th1-biased cellular immune responses against WT1 protein, which was essentially needed for cancer immunotherapy targeting WT1, should be elicited in patients with hematopoietic malignancies.
Assuntos
Formação de Anticorpos , Neoplasias Hematológicas/imunologia , Síndromes Mielodisplásicas/genética , Células Th1/imunologia , Proteínas WT1/genética , Proteínas WT1/imunologia , Neoplasias Hematológicas/genética , Humanos , Imunoglobulina G/sangue , Leucemia/genética , Leucemia/imunologia , Linfócitos/imunologia , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/imunologia , Valores de ReferênciaRESUMO
When foot-and-mouth-disease (FMD) was identified in Miyazaki prefecture in March 2000, Japan conducted an intensive serological and clinical survey in the areas surrounding the index herd. As a result of the survey during the 21 days of the movement-restriction period, two infected herds were detected and destroyed; there were no other cases in the months that followed. To evaluate the survey used for screening the disease-control area and surveillance area, we estimated the herd-level sensitivity of the survey (HSe) through a spreadsheet model using Monte-Carlo methods. The Reed-Frost model was incorporated to simulate the spread of FMD within an infected herd. In the simulations, 4, 8 and 12 effective-contact scenarios during the 5-day period were examined. The estimated HSes of serological tests (HSeE) were 71.0, 75.3 and 76.3% under the 4, 8 and 12 contact scenarios, respectively. The sensitivity analysis showed that increasing the number of contacts beyond 12 did not improve HSeE, but increasing the number of sampled animals and delaying the dates of sampling did raise HSeEs. Small herd size in the outbreak area (>80% of herds have <20 animals) seems to have helped in maintaining HSeE relatively high, although the serological inspection was carried out before sero-positive animals had a chance to increase in infected herds. The estimated herd-level specificity of serological tests (HSpE) was 98.6%. This HSpE predicted 224 false-positive herds (5th percentile estimate was 200 and 95th percentile was 249), which proved close to the 232 false-positive herds actually observed. The combined-test herd-level sensitivity (serological and clinical inspections combined; CTHSe), averaged 85.5, 87.6 and 88.1% for the 4, 8 and 12 contact scenarios, respectively. Using these CTHSes, the calculated probability that no infected herd was overlooked by the survey was > or =62.5% under the most-conservative, four-contact scenario. The probability that no more than one infected herd was overlooked was > or =89.7%.
Assuntos
Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/prevenção & controle , Surtos de Doenças/veterinária , Febre Aftosa/epidemiologia , Febre Aftosa/prevenção & controle , Programas de Rastreamento/veterinária , Animais , Bovinos , Doenças dos Bovinos/sangue , Doenças dos Bovinos/etiologia , Surtos de Doenças/prevenção & controle , Febre Aftosa/sangue , Febre Aftosa/etiologia , Vírus da Febre Aftosa/isolamento & purificação , Japão/epidemiologia , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Método de Monte Carlo , Sensibilidade e EspecificidadeRESUMO
Respiration and the muscle pump play major roles in increasing venous return. However, the relative contribution of each of these factors remains unclear. The present study investigates the quantitative effects of interaction between respiration and the muscle pump on femoral venous blood flow (FVBF) during a single voluntary knee extension-flexion (KEF) using duplex-Doppler ultrasound. During various respiration modes, which consisted of arrested respiration, normal respiration and deep respiration (inspiration or expiration), eight subjects performed a supine one-legged voluntary KEF. FVBF was measured during respiration only (Protocol A) and during KEF synchronized with respiration (Protocol B). The difference between FVBF values obtained in Protocol B and Protocol A was defined as DeltaFVBF. When KEF was synchronized with normal or deep respiration, FVBF with inspiration was significantly lower than that with expiration. However, DeltaFVBF was significantly higher with inspiration than with expiration during deep respiration but was not significant during normal respiration. Furthermore, DeltaFVBF was significantly higher at both normal and deep respiration than at arrested respiration. The effects upon the venous return during KEF differed between inspiration and expiration. The present findings indicate that during a single supine KEF, respiration might promote venous return to a range of 1.5- to 2.3-fold DeltaFVBF during arrested respiration.
Assuntos
Veia Femoral/fisiologia , Articulação do Joelho/fisiologia , Perna (Membro)/irrigação sanguínea , Contração Muscular/fisiologia , Respiração , Adulto , Humanos , Articulação do Joelho/irrigação sanguínea , Perna (Membro)/diagnóstico por imagem , Masculino , Músculos/fisiologia , Ultrassom , UltrassonografiaRESUMO
IL-12 was recently shown to induce CCR5 on TCR-triggered mouse T cells. Considering that STAT4 is the most critical of IL-12 signaling molecules, this study investigated the role for STAT4 in the induction of CCR5 expression. IL-12R was induced by stimulation with anti-CD3 plus anti-CD28 mAb similarly on T cells from wild-type (WT) and STAT4-deficient (STAT4(-/-)) mice, but the levels of IL-12R induced on IFN-gamma-deficient (IFN-gamma(-/-)) T cells were lower compared with WT T cells. Exposure of TCR-triggered WT T cells to IL-12 induced CCR5 expression. In contrast, TCR-triggered STAT4(-/-) T cells failed to express CCR5 in response to IL-12. IL-12 stimulation induced detectable albeit reduced levels of CCR5 expression on IFN-gamma(-/-) T cells. Addition of rIFN-gamma to cultures of IFN-gamma(-/-) T cells, particularly to cultures during TCR triggering resulted in restoration of CCR5 expression. However, CCR5 expression was not induced in STAT4(-/-) T cells by supplementation of rIFN-gamma. These results indicate that for the induction of CCR5 on T cells, 1) STAT4 plays an indispensable role; 2) such a role is not substituted by simply supplementing rIFN-gamma; and 3) IFN-gamma amplifies CCR5 induction depending on the presence of STAT4.
Assuntos
Proteínas de Ligação a DNA/fisiologia , Interleucina-12/farmacologia , Receptores CCR5/biossíntese , Linfócitos T/imunologia , Transativadores/fisiologia , Animais , Células Cultivadas , Proteínas de Ligação a DNA/genética , Citometria de Fluxo , Humanos , Interferon gama/genética , Interferon gama/farmacologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , RNA Mensageiro/biossíntese , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores CCR5/genética , Receptores de Interleucina/biossíntese , Receptores de Interleucina/genética , Receptores de Interleucina-12 , Fator de Transcrição STAT4 , Transdução de Sinais , Linfócitos T/efeitos dos fármacos , Transativadores/genéticaRESUMO
Pulmonary capillary haemangiomatosis is a rare disorder characterised by multiple angiomatous lesions composed of proliferating capillary vessels in the lung parenchyma that usually progress rapidly to establish fatal pulmonary hypertension. The 29 year old man presented here, however, has been stable for 3.5 years since the diagnosis without symptoms of pulmonary hypertension. High resolution computed tomographic findings of the pulmonary lesions seemed specific to the disease.
Assuntos
Hemangioma Capilar/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Adulto , Progressão da Doença , Hemangioma Capilar/complicações , Hemangioma Capilar/fisiopatologia , Humanos , Hipertensão Pulmonar/etiologia , Pulmão/fisiopatologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/fisiopatologia , Masculino , Intensificação de Imagem Radiográfica , Fatores de Tempo , Tomografia Computadorizada por Raios X , Fator de TransferênciaRESUMO
The chemokine receptor CCR5 has been implicated in the recruitment of T cells to inflammatory sites. However, the regulation of CCR5 induction on T cells and its contribution to T cell adhesiveness are poorly understood. Using a Th1 clone, 2D6, that can be maintained with interleukin (IL)-12 or IL-2 alone (designated 2D6(IL-12) or 2D6(IL-2), respectively), we investigated how CCR5 is induced on T cells and whether CCR5 is responsible for up-regulating the function of adhesion molecules. 2D6(IL-12) grew, forming cell aggregates, in culture containing IL-12. This was due to lymphocyte function-associated antigen (LFA)-1-intercellular adhesion molecule (ICAM)-1 interaction, because 2D6(IL-12) expressed both LFA-1 and ICAM-1 and cell aggregation was inhibited by anti-ICAM-1 monoclonal antibody. Despite comparable levels of LFA-1 and ICAM-1 expression, 2D6(IL-2) cells did not aggregate in culture with IL-2. It is important that there was a critical difference in CCR5 expression between 2D6(IL-12) and 2D6(IL-2); the former expressed high levels of CCR5, and the latter expressed only marginal levels. Both types of cells expressed detectable albeit low levels of RANTES (regulated on activation, normal T expressed and secreted) mRNA. Unlike IL-12 or IL-2, IL-18 induced high levels of RANTES mRNA expression without modulating CCR5 expression. Therefore, combined stimulation with IL-12 and IL-18 strikingly up-regulated 2D6 cell aggregation. Notably, LFA-1-mediated aggregation of 2D6(IL-12) cells was suppressed by anti-CCR5 antibody. These results indicate that IL-12 plays a critical role in CCR5 expression on Th1 cells and consequently contributes to CCR5-mediated activation of LFA-1 molecules.
Assuntos
Adesão Celular , Interleucina-12/fisiologia , Antígeno-1 Associado à Função Linfocitária/fisiologia , Receptores CCR5/biossíntese , Linfócitos T/imunologia , Animais , Anticorpos/farmacologia , Agregação Celular , Quimiocina CCL4 , Quimiocina CCL5/biossíntese , Quimiocina CCL5/genética , Células Clonais , Regulação para Baixo , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-12/imunologia , Interleucina-12/farmacologia , Interleucina-18/imunologia , Interleucina-18/farmacologia , Interleucina-2/farmacologia , Proteínas Inflamatórias de Macrófagos/biossíntese , Proteínas Inflamatórias de Macrófagos/genética , RNA Mensageiro/biossíntese , Receptores CCR5/genética , Receptores CCR5/fisiologia , Linfócitos T/citologia , Regulação para CimaRESUMO
Despite increasing evidence for the role of the chemokine system in leukocyte trafficking, the mechanism underlying the induction of chemokine receptors is poorly understood. Here, we investigated how CCR5, a chemokine receptor implicated in T cell migration to inflammatory sites, is induced in the T cell. CCR5 mRNA was hardly detected in resting T cells and marginally induced following T cell receptor (TCR) stimulation. However, TCR-triggered T cells expressed IL-12 receptor, and stimulation with recombinant IL-12 resulted in high levels of CCR5 expression on both CD4(+) and CD8(+) T cells. In contrast, IL-2 failed to up-regulate CCR5 expression. The effect of IL-12 was selective to CCR5 because IL-12 did not up-regulate CXCR3 expression. Surface expression of CCR5 was shown by staining with anti-CCR5 monoclonal antibody. Stimulation of these CCR5-positive T cells with the relevant chemokine MIP-1 alpha elicited Ca(2+) influx, showing that IL-12-induced CCR5 is functional. These results indicate a critical role for IL-12 in the induction of CCR5 on TCR-triggered T cells.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Interleucina-12/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores CCR5/metabolismo , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Células Cultivadas , Quimiocina CCL4 , Imunofluorescência , Interferon gama/imunologia , Proteínas Inflamatórias de Macrófagos/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores CCR5/genética , Regulação para CimaRESUMO
A survey of Theileria sergenti infections, daily weight gain and conception proportion was conducted in 85 herds of grazing heifers in Japan. Basic information and epidemiological data from participating herds were obtained by mailed questionnaires, which were completed by field veterinarians. The average cumulative incidence and proportion of treated animals in the participating herds were 25.7 and 21.1%, respectively. The average daily weight gain and conception proportion were 0.51 kg per day and 56.9%, respectively. The basic information and epidemiological data had a large range and standard deviation, which reflect the wide diversity of the grazing herds in Japan. Herds with heavy tick infestation had significantly higher cumulative incidence and proportion of treated animals, therefore, this factor can be a good estimator to predict the occurrence and loss by theileriosis of the herds. The present questionnaire survey was useful for obtaining information about herds in different regions, and this survey method can be applied to the research of other animal diseases in Japan.
Assuntos
Theileriose/epidemiologia , Infestações por Carrapato/veterinária , Animais , Bovinos , Feminino , Fertilização , Japão/epidemiologia , Fatores de Risco , Estações do Ano , Inquéritos e Questionários , Theileria , Theileriose/fisiopatologia , Infestações por Carrapato/epidemiologia , Fatores de Tempo , Aumento de PesoRESUMO
IL-12 and IL-18 are both proinflammatory cytokines that contribute to promoting Th1 development and IFN-gamma expression. However, neither IL-12R nor IL-18R is expressed as a functional complex on most resting T cells. This study investigated the molecular mechanisms underlying the induction of an IL-18R complex in T cells. Resting T cells expressed IL-18Ralpha chains but did not exhibit IL-18 binding sites as detected by incubation with rIL-18 followed by anti-IL-18 Ab, suggesting a lack of IL-18Rbeta expression in resting T cells. Although they also failed to express IL-12R, stimulation with anti-CD3 plus anti-CD28 generated IL-12R. Exposure of these cells to IL-12 led not only to up-regulation of IL-18Ralpha expression but also to induction of IL-18R binding sites on both CD4(+) and CD8(+) T cells concomitant with IL-18Rbeta mRNA expression. The IL-18 binding site represented a functional IL-18R complex capable of exhibiting IL-18 responsiveness. IL-12 induction of an IL-18R complex and IL-18Rbeta mRNA expression was not observed in STAT4-deficient (STAT4(-/-)) T cells and was substantially decreased in IFN-gamma(-/-) T cells. However, the failure of STAT4(-/-) T cells to induce an IL-18R complex was not corrected by IFN-gamma. These results indicate that STAT4 and IFN-gamma play an indispensable role and a role as an amplifying factor, respectively, in IL-12 induction of the functional IL-18R complex.
Assuntos
Adjuvantes Imunológicos/fisiologia , Proteínas de Ligação a DNA/fisiologia , Interferon gama/fisiologia , Interleucina-12/fisiologia , Receptores de Interleucina/biossíntese , Transdução de Sinais/imunologia , Transativadores/fisiologia , Adjuvantes Imunológicos/biossíntese , Adjuvantes Imunológicos/deficiência , Adjuvantes Imunológicos/genética , Animais , Sítios de Ligação/genética , Sítios de Ligação/imunologia , Células Cultivadas , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Interferon gama/biossíntese , Interferon gama/deficiência , Interferon gama/genética , Interleucina-12/metabolismo , Subunidade alfa de Receptor de Interleucina-18 , Interfase/genética , Interfase/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , NF-kappa B/metabolismo , RNA Mensageiro/biossíntese , Receptores de Antígenos de Linfócitos T/fisiologia , Receptores de Interleucina/metabolismo , Receptores de Interleucina-18 , Fator de Transcrição STAT4 , Linfócitos T/imunologia , Linfócitos T/metabolismo , Transativadores/deficiência , Transativadores/genética , Regulação para Cima/imunologiaRESUMO
The activation of resting T cells for the acquisition of various functions depends on whether CD28 costimulatory signals are provided upon T cell receptor stimulation. Here, we investigated how CD28 costimulation functions to allow TCR-triggered resting T cells to acquire IL-12 responsiveness. When T cells are stimulated with low doses of anti-CD3 mAb, CD28 costimulation was required for the optimal levels of IL-12 receptor (IL-12R) expression. However, stimulation of T cells with high doses of anti-CD3 alone induced comparable levels of IL-12R expression to those induced upon CD28 costimulation. Nevertheless, there was a substantial difference in IL-12 responsiveness between these two groups of T cells: compared to anti-CD28-costimulated T cells, T cells that were not costimulated with anti-CD28 exhibited decreased levels of Janus kinases (JAK) JAK2/TYK2 and STAT4 phosphorylation and IFN-y production following IL-12 stimulation. Importantly, STAT6 phosphorylation following IL-4 stimulation was not decreased in anti-CD28-uncostimulated T cells. These resutls indicate that CD28 costimulation not only contributes to up-regulating IL-12R expression but is also required to render JAKs/STAT4 responsive to IL-12 stimulation.
Assuntos
Antígenos CD28/metabolismo , Proteínas de Ligação a DNA/metabolismo , Interleucina-12/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Interleucina/metabolismo , Linfócitos T/efeitos dos fármacos , Transativadores/metabolismo , Animais , Western Blotting , Células Cultivadas , Ativação Enzimática/efeitos dos fármacos , Citometria de Fluxo , Interferon gama/metabolismo , Interleucina-4/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Interleucina-12 , Fator de Transcrição STAT4 , Fator de Transcrição STAT6 , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/citologia , Linfócitos T/enzimologia , Linfócitos T/metabolismoRESUMO
To elucidate the process of TCR-mediated signaling pathways in lipid rafts, we constructed a chimeric molecule that localizes activated SHP-1 to rafts. Raft targeting of activated SHP-1 in Jurkat-derived transfectants completely inhibited the expression of CD69 and transcriptional factors after TCR cross-linking. Whereas the inducible tyrosine phosphorylation of TCR zeta and ZAP-70 and the kinase activity of Lck were intact, phosphorylated LAT was rapidly dephosphorylated by raft targeting of activated SHP-1, leading to defects in LAT activation and subsequent downstream signaling events. Intriguingly, recruitment of endogenous SHP-1 to rafts and its association with LAT were dramatically increased after TCR engagement, suggesting that SHP-1 is involved in raft-mediated T cell activation.