RESUMO
Interferon regulatory factor 5 (IRF5) is a master regulator of macrophage phenotype and a key transcription factor involved in expression of proinflammatory cytokine responses to microbial and viral infection. Here, we show that IRF5 controls cellular and metabolic responses. By integrating ChIP sequencing (ChIP-Seq) and assay for transposase-accessible chromatin using sequencing (ATAC)-seq data sets, we found that IRF5 directly regulates metabolic genes such as hexokinase-2 (Hk2). The interaction of IRF5 and metabolic genes had a functional consequence, as Irf5-/- airway macrophages but not bone marrow-derived macrophages (BMDMs) were characterized by a quiescent metabolic phenotype at baseline and had reduced ability to utilize oxidative phosphorylation after Toll-like receptor (TLR)-3 activation, in comparison to controls, ex vivo. In a murine model of influenza infection, IRF5 deficiency had no effect on viral load in comparison to wild-type controls but controlled metabolic responses to viral infection, as IRF5 deficiency led to reduced expression of Sirt6 and Hk2. Together, our data indicate that IRF5 is a key component of AM metabolic responses following influenza infection and TLR-3 activation.
Assuntos
Metabolismo Energético/imunologia , Regulação da Expressão Gênica/imunologia , Fatores Reguladores de Interferon/imunologia , Macrófagos/imunologia , Sistema Respiratório/citologia , Animais , Células Cultivadas , Sequenciamento de Cromatina por Imunoprecipitação/métodos , Metabolismo Energético/genética , Feminino , Hexoquinase/genética , Hexoquinase/imunologia , Hexoquinase/metabolismo , Humanos , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Sirtuínas/genética , Sirtuínas/imunologia , Sirtuínas/metabolismo , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/imunologia , Receptor 3 Toll-Like/metabolismoRESUMO
BACKGROUND: Rhinoviruses from the Enterovirus genus cause frequent infections and induce remarkably high titres of anticapsid antigen antibodies in asthmatics, while the prevalence of neutralising antibodies to the gut-trophic echoviruses from the same genus is diminished. OBJECTIVE: To assess the absolute and specific antibody titres to VP1 antigens of the gut-trophic enteroviruses, echovirus 30 and Sabin 1 poliovirus, in asthmatic and non-asthmatic children. METHODS: Recombinant polypeptides representing the VP1 capsid antigens of echovirus 30 and Sabin poliovirus 1 were produced. Their ability to bind IgG1 antibodies from the plasma of asthmatic (n = 45) and non-asthmatic (n = 29) children were quantitated by immunoassays that incorporated immunoabsorptions to remove cross-reactivity. RESULTS: The IgG1 antibody titres and prevalence of antibody binding to echovirus 30 were significantly lower for asthmatic children compared to controls (P < 0.05) and inversely correlated with total IgE levels for the whole study population (r = -0.262; P < 0.05). There was no difference in the prevalence and titre between groups to the VP1 antigen of Sabin poliovirus. Anti-tetanus toxoid titres measured for comparison did not correlate with anti-echovirus or poliovirus, but correlated with anti-rhinovirus titres in controls but not asthmatics, where the titres were higher for the asthmatic group. CONCLUSIONS AND CLINICAL RELEVANCE: The associations of lower antibody titres of asthmatic children to echovirus reported here and those of our previous findings of a heightened response to rhinovirus suggest a dichotomy where respiratory enterovirus infection/immunity increases the probability of developing asthma and enteric infections lower the risk. This provides further support for the concept of intestinal infection playing a key role in the development of allergic respiratory disease.
Assuntos
Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Asma/imunologia , Infecções por Echovirus/imunologia , Enterovirus Humano B/imunologia , Imunoglobulina G/imunologia , Anticorpos Antivirais/sangue , Antígenos Virais/sangue , Asma/sangue , Asma/etiologia , Proteínas do Capsídeo/sangue , Proteínas do Capsídeo/imunologia , Criança , Pré-Escolar , Infecções por Echovirus/sangue , Infecções por Echovirus/complicações , Enterovirus Humano B/metabolismo , Feminino , Humanos , Imunoglobulina G/sangue , MasculinoRESUMO
Aerial predation is a highly complex, three-dimensional flight behavior that affects the individual fitness and population dynamics of both predator and prey. Most studies of predation adopt either an ecological approach in which capture or survival rates are quantified, or a biomechanical approach in which the physical interaction is studied in detail. In the present study, we show that combining these two approaches provides insight into the interaction between hunting dragonflies (Libellula cyanea) and their prey (Drosophila melanogaster) that neither type of study can provide on its own. We performed >2500 predation trials on nine dragonflies housed in an outdoor artificial habitat to identify sources of variability in capture success, and analyzed simultaneous predator-prey flight kinematics from 50 high-speed videos. The ecological approach revealed that capture success is affected by light intensity in some individuals but that prey density explains most of the variability in success rate. The biomechanical approach revealed that fruit flies rarely respond to approaching dragonflies with evasive maneuvers, and are rarely successful when they do. However, flies perform random turns during flight, whose characteristics differ between individuals, and these routine, erratic turns are responsible for more failed predation attempts than evasive maneuvers. By combining the two approaches, we were able to determine that the flies pursued by dragonflies when prey density is low fly more erratically, and that dragonflies are less successful at capturing them. This highlights the importance of considering the behavior of both participants, as well as their biomechanics and ecology, in developing a more integrative understanding of organismal interactions.
Assuntos
Fenômenos Ecológicos e Ambientais , Voo Animal/fisiologia , Insetos/fisiologia , Comportamento Predatório/fisiologia , Animais , Fenômenos Biomecânicos/fisiologia , Drosophila/fisiologia , Ecossistema , Movimento/fisiologiaRESUMO
Herpes simplex virus (HSV) hepatitis has a fatal impact on the outcome of organ transplanted recipients. Here, we present a thought-provoking case of HSV hepatitis in a high-risk recipient after living-related liver transplantation (LRLT). A 1-month-old female newborn infant was affected by HSV encephalitis. Fulminant hepatic failure (FHF) of unknown etiology occurred suddenly at 4.4 years of age. Viral infections were ruled out as the cause of FHF. Intensive care including plasma exchange (PE) was started, and the preoperative treatments for ABO incompatibility were performed. Thereafter, LRLT was performed emergently. Although strong immunosuppression for ABO incompatibility was continued after LRLT, antibody-mediated rejection (AMR) occurred on postoperative day (POD) 4. PE was repeated and improvements were obtained. However, liver dysfunction appeared on POD 8. Histopathological findings of liver needle biopsy clearly revealed HSV hepatitis, although the results of HSV DNA and antibody titer in blood sample did not clearly indicate HSV infection. On POD 21, thrombotic microangiopathy (TMA) occurred and the plasma and immunoglobulin were replenished. Our pediatric recipient recovered successfully from AMR, HSV hepatitis, TMA, and repeated sepsis. We conclude that well considered therapy based on the real-time detection of HSV hepatitis is indispensable for the further improvements of outcome in HSV hepatitis after LRLT.
Assuntos
Hepatite Viral Humana/virologia , Falência Hepática Aguda/etiologia , Transplante de Fígado/efeitos adversos , Simplexvirus , Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Pré-Escolar , Encefalite por Herpes Simples/complicações , Encefalite por Herpes Simples/virologia , Feminino , Hepatite Viral Humana/tratamento farmacológico , HumanosRESUMO
Topological defects are found ubiquitously in various kinds of matter, such as vortices in type-II superconductors, and magnetic skyrmions in chiral ferromagnets. While knowledge on the static behavior of magnetic skyrmions is accumulating steadily, their dynamics under forced flow is still a widely open issue. Here, we report the deformation of the moving magnetic skyrmion lattice in MnSi under electric current flow observed using small-angle neutron scattering. A spatially inhomogeneous rotation of the skyrmion lattice, with an inverse rotation sense for opposite sample edges, is observed for current densities greater than a threshold value j t ~ 1 MA m-2 (106 A m-2). Our result show that skyrmion lattices under current flow experience significant friction near the sample edges due to pinning, this being a critical effect that must be considered for anticipated skyrmion-based applications at the nanoscale.
RESUMO
We have examined mononuclear cell preparations from patients with chronic myeloid leukemia [CML] for binding of and response to 1,25-dihydroxycholecalciferol [1,25-(OH)2D3]. Whole cells specifically took up [3H]-1,25-(OH)2D3 with high affinity (Kd 3.6 X 10(-11) M) and low capacity. Subcellular fractionation of labeled cells showed that binding was restricted to cytosols and nuclei. Sucrose gradient centrifugation of cells preincubated with [3H]-1,25-(OH)2D3 revealed a single 3.6S peak which was totally displaced with 100-fold excess nonradioactive hormone. However, we were unable to demonstrate specific binding of 1,25-(OH)2D3 by postlabeling standard cytosol preparations. In addition, cytosols prepared from a mixture of CML cells and 1,25-(OH)2D3 receptor-positive T47D (human breast cancer) cells had less than 10% of the binding measured in T47D cytosol alone. However, the levels of binding in T47D cytosols were not reduced if the receptors were occupied with [3H]-1,25-(OH)2D3 prior to the addition of the CML cytosols. Thus, CML cells appear to contain both the receptor for 1,25-(OH)2D3 and an unknown substance which prevents its detection following the preparation of cytosol. Cells from patients with CML in the chronic phase specifically bound more 1,25-(OH)2D3 [18.0 +/- 3.2 (S.E.) fmol/10(7) cells] than did those in acute myeloid transformation [7.2 +/- 1.5] or than did cells from patients with acute myeloid leukemia [2.6 +/- 0.8]. Only cells from the first group of patients responded to the addition of 1,25-(OH)2D3 by differentiating along the monocyte-macrophage pathway. We conclude that the differentiation-induction effect of 1,25-(OH)2D3 is likely to depend on adequate levels of receptor and that intact cells rather than cytosol preparations should be studied before cells of a particular tissue are designated as receptor negative.
Assuntos
Calcitriol/metabolismo , Leucemia Mieloide/metabolismo , Receptores de Esteroides/metabolismo , Diferenciação Celular , Citosol/metabolismo , Humanos , Cinética , Monócitos/metabolismo , Receptores de Calcitriol , Receptores de Esteroides/isolamento & purificaçãoRESUMO
Both normal and malignant breast tissue contain the specific receptor for 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). A recent study has shown its presence in 80% of surgically removed breast tumors, although only at low levels. We have measured the 1,25-(OH)2D3 receptor in breast tumors from 68 patients and have found it at similar frequency (75%) but at much higher concentrations (range, less than 1 to 30 fmol/mg protein). This receptor has the same characteristics as that measured in classic 1,25-(OH)2D3 target tissues and was distinguished by sucrose gradient centrifugation from plasma contaminants. Complete case histories and follow-up were available on 56 of these patients, and 1,25-(OH)2D3 receptor status (less than 8 or greater than or equal to 8 fmol/mg protein) was not related to the level of estrogen receptors, menopausal status, T-stage or histology of tumors, or presence of 99mTc phosphate hot spots on bone scans. The lack of relationship between the level of 1,25-(OH)2D3 receptors and other prognostic indicators suggests its potential as a new independent variable for assessing breast cancer patients. However, at this stage, 1,25-(OH)2D3 receptor status did not result in any significant difference in probability of survival or metastasis-free survival. Assessment of the importance of this variable for treatment or outcome must await an increased number of patients and a longer time since surgery.
Assuntos
Neoplasias da Mama/metabolismo , Calcitriol/metabolismo , Receptores de Esteroides/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Citosol/metabolismo , Feminino , Humanos , Menopausa , Receptores de Calcitriol , Receptores de Estrogênio/metabolismoRESUMO
Mechanical control of magnetism is an important and promising approach in spintronics. To date, strain control has mostly been demonstrated in ferromagnetic structures by exploiting a change in magnetocrystalline anisotropy. It would be desirable to achieve large strain effects on magnetic nanostructures. Here, using in situ Lorentz transmission electron microscopy, we demonstrate that anisotropic strain as small as 0.3% in a chiral magnet of FeGe induces very large deformations in magnetic skyrmions, as well as distortions of the skyrmion crystal lattice on the order of 20%. Skyrmions are stabilized by the Dzyaloshinskii-Moriya interaction, originating from a chiral crystal structure. Our results show that the change in the modulation of the strength of this interaction is amplified by two orders of magnitude with respect to changes in the crystal lattice due to an applied strain. Our findings may provide a mechanism to achieve strain control of topological magnetic structures based on the Dzyaloshinskii-Moriya interaction.
RESUMO
Bombesin was injected into the cerebral ventricle of male rats anesthetized with urethane to study its effect on plasma levels of immunoreactive somatostatin (IRS) in hypophysial portal and jugular blood. An intraventricular injection of bombesin (0.2 and 2 micrograms/rat) caused a significant and dose-related increase in plasma IRS in hypophysial portal blood but not in jugular blood. Although bombesin placed into the cerebral ventricle is known to stimulate glucagon and epinephrine release, an iv injection of glucagon (100 micrograms/100 g BW) or epinephrine (2.5 micrograms/100 g BW) did not cause any significant changes in plasma IRS levels in hypophysial portal and jugular blood, suggesting that these substances do not mediate bombesin stimulation of portal IRS release. Pretreatment with naloxone (75 micrograms/100 g BW, iv) failed to affect the portal IRS release induced by bombesin (2 micrograms/rat), indicating that the opiate receptor is not likely to be involved in this reaction. To ascertain whether IRS released by bombesin into hypophysial portal blood is biologically active, the effect of bombesin on the plasma GH level was then examined. Bombesin (2 micrograms/rat) injected intraventricularly completely suppressed the rise of plasma GH after the intraventricular injection of beta-endorphin (1 microgram/rat) or the iv injection of prostaglandin E1 (5 micrograms/100 g BW). Bombesin thus appears to stimulate the secretion of IRS, and probably biologically active somatostatin as well, from the hypothalamus into hypophysial portal blood, thereby inhibiting GH release from the anterior pituitary.
Assuntos
Bombesina/farmacologia , Peptídeos/farmacologia , Hipófise/metabolismo , Somatostatina/metabolismo , Animais , Epinefrina/farmacologia , Glucagon/farmacologia , Masculino , Naloxona/farmacologia , Hipófise/irrigação sanguínea , Hipófise/efeitos dos fármacos , Prostaglandinas E/farmacologia , Radioimunoensaio , Ratos , Somatostatina/análogos & derivadosRESUMO
Synthetic vasoactive intestinal polypeptide (VIP) administered either intraventricularly or iv caused a significant and dose-related increase in plasma PRL levels in urethane-anesthetized rats. The administration of naloxone, an opiate receptor antagonist, significantly blunted the plasma PRL response to VIP. Increases in plasma PRL induced by VIP were also significantly suppressed by L-dopa, a precursor of dopamine, whereas pilocarpine, a cholinergic agonist, diphenhydramine, a histamine antagonist, and cyproheptadine, an antiserotoninergic agent, did not affect the plasma PRL response to VIP. In in vitro experiments, VIP alone did not stimulate PRL release from cultured pituitary cells, but it significantly attenuated the inhibitory action of dopamine, which was not blocked by naloxone. These results suggest that VIP stimulates rat PRL secretion, at least in part, through activation of an opiate receptor in the central nervous system and by blocking the inhibitory action of a dopaminergic mechanism at the pituitary level.
Assuntos
Hormônios Gastrointestinais/farmacologia , Adeno-Hipófise/metabolismo , Prolactina/metabolismo , Peptídeo Intestinal Vasoativo/farmacologia , Animais , Ciproeptadina/farmacologia , Difenidramina/farmacologia , Dopamina/farmacologia , Cinética , Masculino , Naloxona/farmacologia , Pilocarpina/farmacologia , Adeno-Hipófise/efeitos dos fármacos , Prolactina/sangue , RatosRESUMO
The effects of vasoactive intestinal polypeptide (VIP), dopamine, and somatostatin (SRIF) on GH secretion were examined in vitro in perifused pituitary adenoma tissues obtained at surgery from seven patients with acromegaly. The perifusion of VIP at 5 x 10(-8) M resulted in a significant increase in effluent GH levels in five of the seven adenomas. A dose-related GH response was observed from 5 x 10(-9) to 5 x 10(-7) M VIP in two adenomas examined. SRIF at 5 x 10(-8) to 10(-7) M suppressed not only baseline secretion of GH but also inhibited GH rises elicited by VIP in six of the seven adenomas. Dopamine at 5 x 10(-7) to 5 x 10(-6) M decreased the baseline secretion of GH in six of the seven adenomas. In four of the six adenomas responsive to dopamine, dopamine suppressed VIP-induced GH release when perifused simultaneously. In the remaining two dopamine-sensitive adenomas in which VIP alone failed to affect GH release, the inhibition by dopamine of GH release was blocked by VIP perifused concomitantly with dopamine. Synthetic TRH or theophylline perifused at the end of the experiment stimulated GH release in all of the adenomas, indicating the viability of tumor cells throughout the study. These results suggest that VIP stimulates GH release by its direct action on pituitary adenoma cells of acromegalic patients and that VIP, SRIF, and dopamine interact at the pituitary level in modulating GH secretion from these adenomas.
Assuntos
Acromegalia/metabolismo , Adenoma/metabolismo , Hormônios Gastrointestinais/farmacologia , Hormônio do Crescimento/metabolismo , Neoplasias Hipofisárias/metabolismo , Peptídeo Intestinal Vasoativo/farmacologia , Adulto , Dopamina/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Somatostatina/farmacologia , Teofilina/farmacologia , Hormônio Liberador de Tireotropina/farmacologiaRESUMO
Immunoreactive human growth hormone-releasing factor (I-hGRF) in human cerebrospinal fluid (CSF) was measured by radioimmunoassay using antiserum specific to the C-terminal portion of hGRF(1-44)NH2. Dilution curves of I-hGRF in the CSF were completely parallel to that of synthetic hGRF(1-44)NH2 standard. On Sephadex G-50 column chromatography a single peak of I-hGRF in the CSF was eluted at the position of synthetic hGRF(1-44)NH2. I-hGRF was present in the CSF of all control patients without any endocrine disease (mean +/- SE, 29.3 +/- 2.0 pg/ml) whereas I-hGRF in the CSF was not detectable (less than 5.8 pg/ml) in any of the patients with hypothalamic germinoma. In all patients with idiopathic GH deficiency, I-hGRF in the CSF was measurable but its concentration (15.1 +/- 1.0 pg/ml) was significantly (p less than 0.05) lower than that in the control subjects. No difference in I-hGRF levels of the CSF was observed between patients with acromegaly and control subjects. These findings demonstrate for the first time that I-hGRF is present in human CSF. Measurement of I-hGRF in the CSF may be useful for understanding the pathophysiology of hypothalamo-pituitary diseases.
Assuntos
Hormônio Liberador de Hormônio do Crescimento/líquido cefalorraquidiano , Acromegalia/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Criança , Disgerminoma/líquido cefalorraquidiano , Feminino , Hormônio do Crescimento/deficiência , Humanos , Neoplasias Hipotalâmicas/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/análise , RadioimunoensaioRESUMO
We examined ten cellular or tissue sources of lymphocytes for specific binding of 1,25(OH)2D3, the hormonally active form of vitamin D3. A specific-binding protein was found in three of these sources. Scatchard analysis of cytosol from a follicular lymphoma cell line revealed binding sites with a Kd of 7.0 X 10(-11) and a receptor concentration of 6.6 fmol/mg protein. Sucrose density centrifugation of 3H-1,25(OH)2D3 labeled cytosol showed a 3.75 peak which was absent in cytosols incubated with excess nonradioactive 1,25(OH)2D3. The relative amounts of vitamin D3 metabolites required to displace 50% of the specifically bound 3H-1,25(OH)2D3 were 1,25(OH)2D3: 1,24,25(OH)3D3: 25(OH)D3: 24,25(OH)2D3 = 1: 180: 1000: 2700. Excess vitamin D3, cortisol, and estradiol failed to displace 3H-1,25(OH)2D3. Scatchard analysis of spleen cytosol from a patient with prolymphocytic transformation of chronic lymphocytic leukemia demonstrated a binding protein with a Kd of 1.2 X 10(-10) and a receptor concentration of 0.2 fmol/mg protein. DNA cellulose binding confirmed the presence of the specific-binding protein in this cytosol. Specific binding of 3H-1,25(OH)2D3 was also quantitated in a cell line from a patient with Burkitt's lymphoma with a Kd of 0.3 X 10(-10) and a receptor concentration of 29.6 fmol/mg protein. No specific binding of 3H-1,25(OH)2D3 was observed in lymphocytes from seven other malignant and nonmalignant sources. These results are the first to demonstrate a specific-binding protein for 1,25(OH)2D3 in lymphocytes from tissue and from these specific cell lines. The presence of this protein in some lymphocytes but not others may reflect the state of activation of the lymphocytes.
Assuntos
Linfócitos/metabolismo , Receptores de Esteroides/metabolismo , Ligação Competitiva , Linhagem Celular , Humanos , Técnicas In Vitro , Leucemia Linfoide/metabolismo , Linfoma/metabolismo , Receptores de CalcitriolRESUMO
Effect of [Asu 1,7]eel calcitonin (CT) on prolactin (PRL) release was examined in male rats under urethane anesthesia. Intravenous injection of 4-20 micrograms [Asu1,7]eel CT did not modify plasma PRL levels. Injections of 0.5-2.5 micrograms [Asu1,7]eel CT into the lateral ventricle produce a significant and dose-related increase of plasma PRL within 10 min of injection. When intraventricularly injected in an equimolar dose (0.74 nmol/10 microliters), eel CT11-32, eel CT15-32, [Asu1,7]eel CT1-16 and [Asu1,7]eel CT1-9 showed 44.8, 25.7, 19.9 and 10.1% the potencies of [Asu1,7]eel CT, respectively, in stimulating activity of PRL release. The rise of plasma PRL after [Asu1,7]eel CT injection were significantly less or abolished not only in hypothalamic-lesioned rats but also in rats with complete deafferentation. Pretreatment with alpha-methyl-p-tyrosine (250 mg/kg, 12 h before) but not with p-chlorophenylalanine (300 mg/kg, 72 and 24 h before) resulted in a suppression of [Asu1,7]eel CT-induced PRL release. These results suggest the following: first, PRL release is stimulated by centrally injected [Asu1,7]eel CT, the action site of which may exist in the extrahypothalamic area; second, brain catecholamines may be involved in the mechanism of [Asu1,7]eel CT-evoked PRL release; third, the C-terminal portion of the peptide may play an important role in stimulating PRL release.
Assuntos
Calcitonina/farmacologia , Hipotálamo/metabolismo , Prolactina/metabolismo , Animais , Fenclonina/farmacologia , Injeções Intravenosas , Injeções Intraventriculares , Masculino , Metiltirosinas/farmacologia , Fragmentos de Peptídeos/farmacologia , Ratos , Ratos Endogâmicos , Relação Estrutura-Atividade , alfa-MetiltirosinaRESUMO
The color Doppler flow imaging (CDFI) technique was used to study the dynamics of cerebrospinal fluid (CSF) flow in 13 infants with intracranial hemorrhage. CDFI was performed 46 times in 6 intraventricular hemorrhage (IVH) patients and 7 subarachnoid hemorrhage (SAH) patients with or without subdural hemorrhage during different stages. CSF flow was observed in 8 infants with IVH (5) or SAH (3) on CDFI. CSF flow in the aqueduct, third ventricle and foramen of Monro was visualized in both the upward and downward directions, primarily reflecting respiration and/or cardiac pulsation in the acute stage. It is suggested that CDFI may allow evaluation of the CSF flow dynamics and an early diagnosis of intracranial hemorrhage in infants.
Assuntos
Hemorragia Cerebral/líquido cefalorraquidiano , Hemorragia Cerebral/diagnóstico por imagem , Ventrículos Cerebrais/diagnóstico por imagem , Eletrocardiografia , Feminino , Hematoma Subdural/líquido cefalorraquidiano , Hematoma Subdural/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Masculino , Hemorragia Subaracnóidea/líquido cefalorraquidiano , Hemorragia Subaracnóidea/diagnóstico por imagem , Ultrassonografia Doppler TranscranianaRESUMO
Traditional methods of monitoring sedated pediatric dental patients have major shortcomings. This study evaluated the use of capnography in conjunction with pulse oximetry for monitoring children during conscious sedation for dental treatment. The specific purposes of the study were to determine if capnography would: (1) detect ventilatory changes that subsequently cause an oxyhemoglobin desaturation as detected by pulse oximetry; and (2) detect an airway obstruction. Ten pediatric dental patients (mean age 2 years, 10 months) were sedated with 75 mg/kg of chloral hydrate in strict accordance with the Guidelines for the Elective Use of Conscious Sedation, Deep Sedation, and General Anesthesia in Pediatric Patients of the American Academy of Pediatric Dentistry and the American Academy of Pediatrics (1985). All patients were monitored continuously using both capnography and pulse oximetry. Analysis of data obtained using these monitors revealed that specific end-tidal CO2 values were not predictive for subsequent oxyhemoglobin desaturations and that capnography was very accurate in detecting complete obstruction of the airway. Pulse oximetry revealed that all patients had mild oxyhemoglobin desaturations and that 50% had moderate desaturations.
Assuntos
Anestesia Dentária , Dióxido de Carbono/análise , Oximetria , Medicação Pré-Anestésica , Pré-Escolar , Estudos de Avaliação como Assunto , Feminino , Humanos , MasculinoRESUMO
We recently reported that microRNA (miR)-145 is downregulated and induces apoptosis in human bladder cancer cells. Also, it is suggested that the ectopic expression of miR-145 induces apoptosis with the induction of TRAIL expression in several cancer cells. Here, we demonstrated a novel mechanism of apoptosis induction by miR-145 in bladder cancer cells. Exogenous miR-145 in T24 and NKB1 cells markedly increased the expression levels of interferon (IFN)-ß, 2'-5'-oligoadenylate synthetase 1, which lies upstream of 2'-5' oligoadenylates/RNase L system, and TRAIL, and induced apparent caspase-dependent apoptosis that was suppressed by cotreatment with a pan-caspase inhibitor; moreover, these expression levels were reduced by cotreatment with an miR-145 inhibitor. The apoptosis did not depend on Toll-like receptor 3 (TLR3) expression, because TLR3-silencing failed to inhibit IFN-ß induction by miR-145. Then, we focused on the suppressor of cytokine signaling 7 (socs7), whose expression level was upregulated in bladder cancer cells compared with its level in normal human urothelial cells, as a putative target gene involved in IFN-ß induction by miR-145. Expectedly, exogenous miR-145 decreased the expression level of SOCS7, and socs7-silencing enhanced IFN-ß induction by transfection with a TLR3 ligand, polyinosinic acid-polycytidylic acid (PIC). The results of a luciferase reporter assay revealed that miR-145 targeted socs7. In addition, socs7-silencing significantly decreased the level of p-Akt and suppressed the growth of T24 cells. Furthermore, exogenous miR-145 or socs7-silencing promoted nuclear translocation of STAT3. In conclusion, the machinery of IFN-ß induction through the regulation of SOCS7 by miR-145 was closely associated with the induction of apoptosis. Moreover, exogenous miR-145 promoted IFN-ß induction by targeting socs7, which resulted in the nuclear translocation of STAT3. Additionally, our data indicate that SOCS7 functioned as an oncogene, the finding that revealed a novel mechanism of carcinogenesis in bladder cancer cells.
Assuntos
Apoptose/efeitos dos fármacos , Interferon beta/metabolismo , MicroRNAs/farmacologia , Proteínas Nucleares/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , 2',5'-Oligoadenilato Sintetase/metabolismo , Caspases/metabolismo , Linhagem Celular , Núcleo Celular/metabolismo , Humanos , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Poli I-C/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteínas Supressoras da Sinalização de Citocina/antagonistas & inibidores , Proteínas Supressoras da Sinalização de Citocina/genética , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Receptor 3 Toll-Like/antagonistas & inibidores , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/metabolismo , Regulação para Cima/efeitos dos fármacos , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologiaRESUMO
The dynamics of predator-prey interactions vary enormously, due both to the heterogeneity of natural environments and to wide variability in the sensorimotor systems of predator and prey. In addition, most predators pursue a range of different types of prey, and most organisms are preyed upon by a variety of predators. We do not yet know whether predators employ a general kinematic and behavioral strategy, or whether they tailor their pursuits to each type of prey; nor do we know how widely prey differ in their survival strategies and sensorimotor capabilities. To gain insight into these questions, we compared aerial predation in 4 species of libelluid dragonflies pursuing 4 types of dipteran prey, spanning a range of sizes. We quantified the proportion of predation attempts that were successful (capture success), as well as the total time spent and the distance flown in pursuit of prey (capture efficiency). Our results show that dragonfly prey-capture success and efficiency both decrease with increasing size of prey, and that average prey velocity generally increases with size. However, it is not clear that the greater distances and times required for capturing larger prey are due solely to the flight performance (e.g., speed or evasiveness) of the prey, as predicted. Dragonflies initiated pursuits of large prey when they were located farther away, on average, as compared to small prey, and the total distance flown in pursuit was correlated with initial distance to the prey. The greater initial distances observed during pursuits of larger prey may arise from constraints on dragonflies' visual perception; dragonflies typically pursued prey subtending a visual angle of 1°, and rarely pursued prey at visual angles greater than 3°. Thus, dragonflies may be unable to perceive large prey flying very close to their perch (subtending a visual angle greater than 3-4°) as a distinct target. In comparing the performance of different dragonfly species that co-occur in the same habitat, we found significant differences that are not explained by body size, suggesting that some dragonflies may be specialized for pursuing particular types of prey. Our results underscore the importance of performing comparative studies of predator-prey interactions with freely behaving subjects in natural settings, to provide insight into how the behavior of both participants influences the dynamics of the interaction. In addition, it is clear that gaining a full understanding of predator-prey interactions requires detailed knowledge not only of locomotory mechanics and behavior, but also of the sensory capabilities and constraints of both predator and prey.
Assuntos
Voo Animal/fisiologia , Odonatos/fisiologia , Comportamento Predatório/fisiologia , Percepção Visual/fisiologia , Análise de Variância , Animais , Tamanho Corporal , Dípteros , Feminino , Masculino , Especificidade da Espécie , Fatores de Tempo , Gravação em VídeoRESUMO
Feasibility of a novel exposure system to print serial numbers and two-dimensional code marks was demonstrated. The new system used light-emitting diodes (LEDs) combined with an optical fiber matrix array as a light source. At first, as preparatory experiments, code mark patterns were printed using a prototype exposure system without using the optical fiber array but using the combination of arrayed LEDs with a central wavelength of 428 nm, spherical lenses, and rod lenses. Although the code mark patterns were successfully printed, it took too much exposure time. For this reason, bullet-type LEDs with a high power and a shorter wavelength of 405 nm were used and the optical fiber matrix array was adopted. Because the emitted light rays were efficiently taken into the fiber, and the resist sensitivity was improved, practically available short exposure time of less than 2 s was obtained.