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Blazars are active galactic nuclei (AGN) with relativistic jets whose non-thermal radiation is extremely variable on various timescales1-3. This variability seems mostly random, although some quasi-periodic oscillations (QPOs), implying systematic processes, have been reported in blazars and other AGN. QPOs with timescales of days or hours are especially rare4 in AGN and their nature is highly debated, explained by emitting plasma moving helically inside the jet5, plasma instabilities6,7 or orbital motion in an accretion disc7,8. Here we report results of intense optical and γ-ray flux monitoring of BL Lacertae (BL Lac) during a dramatic outburst in 2020 (ref. 9). BL Lac, the prototype of a subclass of blazars10, is powered by a 1.7 × 108 MSun (ref. 11) black hole in an elliptical galaxy (distance = 313 megaparsecs (ref. 12)). Our observations show QPOs of optical flux and linear polarization, and γ-ray flux, with cycles as short as approximately 13 h during the highest state of the outburst. The QPO properties match the expectations of current-driven kink instabilities6 near a recollimation shock about 5 parsecs (pc) from the black hole in the wake of an apparent superluminal feature moving down the jet. Such a kink is apparent in a microwave Very Long Baseline Array (VLBA) image.
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Blazars are active galactic nuclei, which are powerful sources of radiation whose central engine is located in the core of the host galaxy. Blazar emission is dominated by non-thermal radiation from a jet that moves relativistically towards us, and therefore undergoes Doppler beaming. This beaming causes flux enhancement and contraction of the variability timescales, so that most blazars appear as luminous sources characterized by noticeable and fast changes in brightness at all frequencies. The mechanism that produces this unpredictable variability is under debate, but proposed mechanisms include injection, acceleration and cooling of particles, with possible intervention of shock waves or turbulence. Changes in the viewing angle of the observed emitting knots or jet regions have also been suggested as an explanation of flaring events and can also explain specific properties of blazar emission, such as intra-day variability, quasi-periodicity and the delay of radio flux variations relative to optical changes. Such a geometric interpretation, however, is not universally accepted because alternative explanations based on changes in physical conditions-such as the size and speed of the emitting zone, the magnetic field, the number of emitting particles and their energy distribution-can explain snapshots of the spectral behaviour of blazars in many cases. Here we report the results of optical-to-radio-wavelength monitoring of the blazar CTA 102 and show that the observed long-term trends of the flux and spectral variability are best explained by an inhomogeneous, curved jet that undergoes changes in orientation over time. We propose that magnetohydrodynamic instabilities or rotation of the twisted jet cause different jet regions to change their orientation and hence their relative Doppler factors. In particular, the extreme optical outburst of 2016-2017 (brightness increase of six magnitudes) occurred when the corresponding emitting region had a small viewing angle. The agreement between observations and theoretical predictions can be seen as further validation of the relativistic beaming theory.
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A new type of Mach-Zehnder interferometer device based on in-fiber optical waveguides, fabricated by direct femtosecond laser pulse inscription in a single-mode fiber has been demonstrated and successfully employed for temperature and strain measurement. The in-fiber waveguide can couple the light out from the fiber core and guide it along the cladding region before directing it back into the fiber core. Such an inner structured interferometer device is compact and robust, can be constructed in a flexible and precisely controlled manner, and hence is expected to have many potential applications.
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Some polymorphisms of the human CETP gene are causally and significantly associated with serum lipids levels; however, the information regarding this gene in pigs is sparse. To evaluate the effects of CETP on blood lipid traits and fat deposition in pig, porcine CETP tissue expression patterns were observed by quantitative real-time polymerase chain reaction (qPCR) first. High expression was detected in liver, spleen, gluteus medius (GM) muscle and backfat. A de novo polymorphism (AF333037:g.795C>T) in the intron 1 region of porcine CETP was identified. This polymorphism was further genotyped by direct sequencing of the PCR products of 390 Wannan Black pigs, a Chinese native breed population. Association analyses at 45 and 300 days of age revealed highly significant associations between CETP genotypes and serum lipid traits. Furthermore, this polymorphism was proved to be associated with differences in liver CETP mRNA levels: pigs at 300 days of age with the TT genotype had higher levels than did those with other genotypes (P = 0.021). Additionally, analysis at 300 days of age showed that GM CETP mRNA expression correlated positively with serum lipids levels as well as with carcass backfat thickness and intramuscular fat content in GM. These results indicate that CETP is involved in serum, adipose and muscle lipid metabolism in pigs. The mechanisms underlying such relationships and their functional implications are worthy of further research.
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Proteínas de Transferencia de Ésteres de Colesterol/genética , Metabolismo de los Lípidos/genética , Polimorfismo Genético , Sus scrofa/genética , Animales , Cruzamiento , Genotipo , Lípidos/sangre , Hígado/metabolismo , Masculino , Carne/análisis , Datos de Secuencia Molecular , Músculo Esquelético/metabolismo , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: We measured breast density (BD) on MRI and correlated with endogenous hormonal levels. PATIENTS AND METHODS: Twenty-four premenopausal women received four weekly breast MRI. A blood sample was collected on the same day of MRI. BD was measured using a computer-based algorithm. The generalized estimation equation method was applied to model mean fibroglandular tissue volume (FV) and mean percent density (PD) from predictor variables including estradiol, progesterone, and week during a cycle. RESULTS: In week 3, a borderline significant correlation between estradiol and PD (r = 0.43, P = 0.04), estradiol and FV (r = 0.40, P = 0.05) and between progesterone and FV (r = 0.42, P = 0.04) was noted. The FV and PD measured in weeks 4 and 1 were higher than in weeks 2 and 3, adjusted for variation in endogenous estradiol and progesterone, indicating that the hormone change could not account for the changes in density. No lag effect of endogenous hormone on the change of FV or PD was noted (all P-values > 0.05). CONCLUSIONS: Our results showed that BD is not strongly associated with the endogenous hormone. Their association with breast cancer risk was likely coming from different mechanisms, and they should be considered as independent risk factors.
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Neoplasias de la Mama/epidemiología , Mama/citología , Mama/fisiología , Estradiol/sangre , Ciclo Menstrual , Progesterona/sangre , Adulto , Femenino , Humanos , Imagenología Tridimensional , Imagen por Resonancia Magnética , Persona de Mediana Edad , Riesgo , Adulto JovenRESUMEN
OBJECTIVE: Reports of the efficacy of induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) on locoregionally advanced nasopharyngeal carcinoma (NPC) are scarce. This study aimed to compare the clinical outcomes of the GP (gemcitabine plus cisplatin) regimen and the TPF (taxane, cisplatin and 5-FU) regimen combined with CCRT in patients with NPC. PATIENTS AND METHODS: This study retrospectively analyzed 827 patients with advanced NPC who received IC combined with CCRT in People's Hospital of Rizhao, China from January 2006 to June 2012. The propensity score method was used to reduce the effects of the observed confounding between the GP and TPF groups. Study end points were disease-free survival (DFS) and overall survival (OS). In total, 694 patients received GP or TPF as the IC treatment program. Propensity score matching identified 166 patients in each cohort. RESULTS: The 5-year OS and DFS rates of the entire cohort were 83.5% and 80.9%, respectively. GP was associated with a significantly improved 5 year OS (87.4% vs. 79.2%, p< 0.001), and DFS (86.2% vs. 78.5%, p< 0.001) rates compared with the TPF group. In the PSM (propensity score-matching) cohort, the GP group showed a significantly better OS (HR, 1.842, 95% CI:1.627-2.588; p= 0.011), and DFS (HR, 1.904, 95% CI: 1.742-2.737; p= 0.004) compared with the TPF group in multivariable analyses. The prevalence of acute adverse events of neutropenia and leukopenia were higher in severe (grade 3-4) adverse blood events in the TPF group (p<0.05). Thrombocytopenia had more adverse reactions in the GP group (p<0.05). The main non-hemotoxicities were nausea and vomiting, while the TPF group was slightly higher (p=0.031). CONCLUSIONS: The clinical efficacy of the GP regimen combined with CCRT for the treatment of locoregionally advanced NPC may be better than that of the TPF regimen.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/uso terapéutico , Desoxicitidina/análogos & derivados , Fluorouracilo/uso terapéutico , Carcinoma Nasofaríngeo/tratamiento farmacológico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Taxoides/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/efectos adversos , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Estudios Retrospectivos , Taxoides/efectos adversos , Factores de Tiempo , GemcitabinaRESUMEN
AIMS/HYPOTHESIS: Rosiglitazone, an insulin sensitiser, not only improves insulin sensitivity but also enhances insulin secretory capacity by ameliorating gluco- and lipotoxicity in beta cells. Rosiglitazone can stimulate insulin secretion at basal and high glucose levels via a phosphatidylinositol 3-kinase (PI3K)-dependent pathway. We hypothesised that regulation of phosphorylation of the ATP-sensitive potassium (K(ATP)) channel might serve as a key step in the regulation of insulin secretion. METHODS: Insulin secretory responses were studied in an isolated pancreas perfusion system, cultured rat islets and MIN6 and RINm5F beta cells. Signal transduction pathways downstream of PI3K were explored to link rosiglitazone to K(ATP) channel conductance with patch clamp techniques and insulin secretion measured by ELISA. RESULTS: Rosiglitazone stimulated AMP-activated protein kinase (AMPK) activity and induced inhibition of the K(ATP) channel conductance in islet beta cells; both effects were blocked by the PI3K inhibitor LY294002. Following stimulation of AMPK by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a pharmacological activator, both AICAR-stimulated insulin secretion and inhibition of K(ATP) channel conductance were unaffected by LY294002, indicating that AMPK activation occurs at a site downstream of PI3K activity. The serine residue at amino acid position 385 of Kir6.2 was found to be the substrate phosphorylation site of AMPK when activated by rosiglitazone or AICAR. CONCLUSIONS/INTERPRETATION: Our data indicate that PI3K-dependent activation of AMPK is required for rosiglitazone-stimulated insulin secretion in pancreatic beta cells. Phosphorylation of the Ser(385) residue of the Kir6.2 subunit of the K(ATP) channel by AMPK may play a role in insulin secretion.
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Proteínas Quinasas Activadas por AMP/metabolismo , Hipoglucemiantes/farmacología , Insulina/metabolismo , Canales KATP/efectos de los fármacos , Canales de Potasio de Rectificación Interna/metabolismo , Serina/metabolismo , Tiazolidinedionas/farmacología , Proteínas Quinasas Activadas por AMP/química , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacología , Animales , Western Blotting , Línea Celular , Cromonas/farmacología , Inhibidores Enzimáticos/farmacología , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Humanos , Inmunoprecipitación , Secreción de Insulina , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Masculino , Morfolinas/farmacología , Fosforilación/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Ribonucleótidos/farmacología , Rosiglitazona , Serina/químicaRESUMEN
We combine spatial variations of P- and S-wave speeds, 1000 fault plane solutions, and 6600 well-determined hypocenters to investigate the nature of subducted lithosphere and deep earthquakes beneath the Tonga back-arc. We show that perplexing patterns in seismicity and fault plane solutions can be accounted for by the juxtaposition of a steep-dipping Wadati-Benioff zone and a subhorizontal remnant of slab that is no longer attached to the actively subducting lithosphere. The detached slab may be from a previous episode of subduction along the fossil Vitiaz trench about 5 to 8 million years ago. The juxtaposition of slabs retains a large amount of subducted material in the transition zone of the mantle. Such a configuration, if common in the past, would allow the preservation of a primordial component in the lower mantle.
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Rheumatoid arthritis (RA) is usually a chronic, systemic inflammatory disorder primarily targeting the synovium and articular cartilage. It is incurable, costly and responds poorly to treatment. Methotrexate alone or in combination with conventional and/or biological disease-modifying antirheumatic drugs (DMARDs) is often used to induce remission of active disease. The effectiveness of treatment is, however, limited and most patients develop chronic disability and require total knee arthroplasty or total hip replacement. Emerging therapies targeting specific cytokines and growth factors in the RA inflammatory cascade offer potent new means of modifying disease activity. Recently, increased concentrations of adipokines, including visfatin, mainly produced by adipocytes in serum and joint synovial fluid, were found in RA patients. Visfatin has important pro-inflammatory and catabolic roles in RA pathogenesis and is now being studied as a potential therapeutic target for RA. Here we discuss the relationship between visfatin and RA and its potential as a therapeutic target for RA.
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Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/enzimología , Inhibidores Enzimáticos/uso terapéutico , Nicotinamida Fosforribosiltransferasa/antagonistas & inhibidores , Citocinas/metabolismo , Inhibidores Enzimáticos/farmacología , Humanos , Especificidad de Órganos/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate the influences of red mold rice (RMR) on obesity and related metabolic abnormalities. METHODS AND RESULTS: The 3T3-L1 cell line was used to examine the effects of RMR extracts on preadipocytes and on mature adipocytes. Both water and ethanol extracts of RMR had inhibitory effects on 3T3-L1 preadipocyte proliferation and differentiation. Water extracts of RMR enhanced the lipolysis activity in mature adipocytes, which negatively correlated with the triglyceride content within cells. RMR treatment did not affect heparin-releasable lipoprotein lipase activity in mature adipocytes. Furthermore, animal studies were carried out to explore the antiobesity effects of RMR. The control group of male Wistar rats were fed regular laboratory feed, whereas the other groups were fed the high-fat (HF) diet supplemented with lovastatin, rice or RMR (0.4 and 2%, w w(-1)). The relative caloric intakes of the control and HF groups were 3.34 and 4.85 kcal g(-1), respectively. After 6 weeks, rats treated with RMR at the 0.4 and 2% doses had lower weight gain and less fat pads mass accompanied with smaller fat cells than did the HF-diet rats. These effects probably resulted from an increase in the lipolysis activity of adipose tissue and a reduction in food/energy consumption. On the other hand, the RMR supplement significantly reduced serum total cholesterol, serum low-density lipoprotein (LDL) cholesterol, the ratio of LDL to high-density lipoprotein (HDL) cholesterol and serum insulin in the HF group. Moreover, the 2% RMR treatment significantly increased serum HDL cholesterol. CONCLUSION: This study reveals for the first time that RMR can prevent body fat accumulation and improve dyslipidemia. The antiobesity effects of RMR mainly derive from the lipolytic activity and mild antiappetite potency of RMR. In addition, extracts of RMR suppressed the proliferation and differentiation in 3T3-L1 preadipocytes, which might have contributed to the inhibition of new adipocyte formation or hyperplasia in adipose tissue.
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Fármacos Antiobesidad/uso terapéutico , Obesidad/prevención & control , Oryza , Fitoterapia , Preparaciones de Plantas/uso terapéutico , Células 3T3-L1/metabolismo , Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Suplementos Dietéticos , Dislipidemias/metabolismo , Dislipidemias/prevención & control , Hiperinsulinismo/metabolismo , Hiperinsulinismo/prevención & control , Masculino , Ratones , Monascus/química , Obesidad/metabolismo , RatasRESUMEN
BACKGROUND AND PURPOSE: Cinnamophilin, a thromboxane A(2) receptor antagonist, has been identified as a prominent anti-arrhythmic agent in rat heart. This study aimed to determine its electromechanical and anti-arrhythmic effects in guinea-pig hearts. EXPERIMENTAL APPROACH: Microelectrodes were used to study action potentials in ventricular papillary muscles. Fluo-3 fluorimetric ratio and whole-cell voltage-clamp techniques were used to record calcium transients and membrane currents in single ventricular myocytes, respectively. Intracardiac electrocardiograms were obtained and the anti-arrhythmic efficacy was determined from isolated perfused hearts. KEY RESULTS: In papillary muscles, cinnamophilin decreased the maximal rate of upstroke (V(max)) and duration of action potential, and reduced the contractile force. In single ventricular myocytes, cinnamophilin reduced Ca(2+) transient amplitude. Cinnamophilin decreased the L-type Ca(2+) current (I(Ca,L))(IC(50)=7.5 microM) with use-dependency, induced a negative shift of the voltage-dependent inactivation and retarded recovery from inactivation. Cinnamophilin also decreased the Na(+) current (I(Na)) (IC(50)=2.7 microM) and to a lesser extent, the delayed outward (I(K)), inward rectifier (I(K1)), and ATP-sensitive (I(K,ATP)) K(+) currents. In isolated perfused hearts, cinnamophilin prolonged the AV nodal conduction interval and Wenckebach cycle length and the refractory periods of the AV node, His-Purkinje system and ventricle, while shortening the ventricular repolarization time. Additionally, cinnamophilin reduced the occurrence of reperfusion-induced ventricular fibrillation. CONCLUSIONS AND IMPLICATIONS: These results suggest that the promising anti-arrhythmic effect and the changes in the electromechanical function induced by cinnamophilin in guinea-pig heart can be chiefly accounted for by inhibition of I(Ca,L) and I(Na).
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Antiarrítmicos/farmacología , Guayacol/análogos & derivados , Corazón/efectos de los fármacos , Lignanos/farmacología , Receptores de Tromboxano A2 y Prostaglandina H2/antagonistas & inhibidores , Animales , Canales de Calcio Tipo L/efectos de los fármacos , Canales de Calcio Tipo L/fisiología , Guayacol/farmacología , Cobayas , Sistema de Conducción Cardíaco/efectos de los fármacos , Sistema de Conducción Cardíaco/fisiología , Técnicas In Vitro , Masculino , Músculos Papilares/efectos de los fármacos , Músculos Papilares/fisiología , Canales de Potasio/efectos de los fármacos , Canales de Potasio/fisiología , Canales de Sodio/efectos de los fármacos , Canales de Sodio/fisiologíaRESUMEN
We demonstrate an optical Fabry-Perot interferometer fiber tip sensor based on an etched end of multimode fiber filled with ultraviolet adhesive. The fiber device is miniature (with diameter of less than 60 µm), robust and low cost, in a convenient reflection mode of operation, and has a very high gas pressure sensitivity of -40.94 nm/MPa, a large temperature sensitivity of 213 pm/°C within the range from 55 to 85 °C, and a relatively low temperature cross-sensitivity of 5.2 kPa/°C. This device has a high potential in monitoring environment of high pressure.
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The studies of biological, disease, and pharmacological networks are facilitated by the systems-level investigations using computational tools. In particular, the network descriptors developed in other disciplines have found increasing applications in the study of the protein, gene regulatory, metabolic, disease, and drug-targeted networks. Facilities are provided by the public web servers for computing network descriptors, but many descriptors are not covered, including those used or useful for biological studies. We upgraded the PROFEAT web server http://bidd2.nus.edu.sg/cgi-bin/profeat2016/main.cgi for computing up to 329 network descriptors and protein-protein interaction descriptors. PROFEAT network descriptors comprehensively describe the topological and connectivity characteristics of unweighted (uniform binding constants and molecular levels), edge-weighted (varying binding constants), node-weighted (varying molecular levels), edge-node-weighted (varying binding constants and molecular levels), and directed (oriented processes) networks. The usefulness of the network descriptors is illustrated by the literature-reported studies of the biological networks derived from the genome, interactome, transcriptome, metabolome, and diseasome profiles.
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Redes Reguladoras de Genes , Internet , Proteínas/química , Programas Informáticos , Biología Computacional , Genoma Humano , Humanos , Metaboloma , Modelos Teóricos , Análisis de Secuencia de Proteína , TranscriptomaRESUMEN
Optical Fabry-Perot interferometer sensors based on inner air-cavity is featured with compact size, good robustness and high strain sensitivity, especially when an ultra-thin air-cavity is adopted. The typical shape of Fabry-Perot inner air-cavity with reflection mode of operation is elliptic, with minor axis along with and major axis perpendicular to the fiber length. The first reflection surface is diverging whereas the second one is converging. To increase the visibility of the output interference pattern, the length of major axis should be large for a given cavity length. However, the largest value of the major axis is limited by the optical fiber diameter. If the major axis length reaches the fiber diameter, the robustness of the Fabry-Perot cavity device would be decreased. Here we demonstrate an ultra-thin crescent shaped Fabry-Perot cavity for strain sensing with ultra-high sensitivity and low temperature cross-sensitivity. The crescent-shape cavity consists of two converging reflection surfaces, which provide the advantages of enhanced strain sensitivity when compared with elliptic or D-shaped FP cavity. The device is fabricated by fusion splicing an etched multimode fiber with a single mode fiber, and hence is simple in structure and economic in cost.
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It is well known that semi-solid forming could only obtain coarse-grained microstructure in a few alloy systems with a low melting point, such as aluminum and magnesium alloys. This work presents that semi-solid forming could also produce novel bimodal microstructure composed of nanostructured matrix and micro-sized (CoFe)Ti2 twins in a titanium alloy, Ti62Nb12.2Fe13.6Co6.4Al5.8. The semi-solid sintering induced by eutectic transformation to form a bimodal microstructure in Ti62Nb12.2Fe13.6Co6.4Al5.8 alloy is a fundamentally different approach from other known methods. The fabricated alloy exhibits high yield strength of 1790 MPa and plastic strain of 15.5%. The novel idea provides a new insight into obtaining nano-grain or bimodal microstructure in alloy systems with high melting point by semi-solid forming and into fabricating high-performance metallic alloys in structural applications.
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The single-stranded DNA binding protein from the filamentous bacteriophage cf has been purified and characterized. The first 12 amino acids, resulting from the N-terminal amino acid sequencing analysis of the protein, agree with an open reading frame (ORF) on the cf genome. The ORF contains 294 bp and codes for a 98 a.a. protein of molecular weight 10.8 kDa, consistent with the result from the denaturing protein gel analysis. The protein appears to be a homodimer as evident from the apparent molecular weight of about 22 kDa obtained from native protein gel analysis. The gene location of the protein has been identified as gene V of the cf single stranded genome, same as that from the M13 phage. The GVP of cf shows a strong sequence homology to the ssDNA binding proteins of Ff, IKe and Pf3 filamentous phages. The DNA binding wing of GVP, conserved among the filamentous phages, has been predicted for cf. To further characterize the protein, the GVP-ssDNA complex of cf has been purified from the infected host (Xanthomonas campestris pv. citri) by density gradient centrifugation. Transmission electron microscopy (TEM) images of the complex showed that it is about 1200 nm in length and 9 nm in diameter and it has a highly regular morphology with a central groove shadow running along the entire structure, but without any apparent helical pattern seen in the M13 complex. The GVP-ssDNA complex of cf seems more rigid than that of M13. Our computer modeling study suggested that this difference between the two complexes may be due to the additional 11 or 12 amino acids at the C-terminal end of the cf-GVP.
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Bacteriófagos/metabolismo , ADN Viral/metabolismo , Proteínas de Unión al ADN/metabolismo , Secuencia de Aminoácidos , Bacteriófagos/genética , Secuencia de Bases , ADN de Cadena Simple/metabolismo , ADN de Cadena Simple/ultraestructura , ADN Viral/ultraestructura , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/aislamiento & purificación , Proteínas de Unión al ADN/ultraestructura , Genes Virales/genética , Datos de Secuencia Molecular , Peso Molecular , Sistemas de Lectura Abierta/genética , Mapeo Restrictivo , Análisis de Secuencia , Homología de Secuencia de AminoácidoRESUMEN
GnRH neurons form the final common pathway regulating the secretion of gonadotropins from the anterior pituitary. Since the patterns of gonadotropin release display profound sexual dimorphism among mammals including the rodent, we undertook an ultrastructural analysis to determine whether these neurosecretory cells were differentially innervated between the sexes. As a further exploration of the organization of the neurocircuitry integrating GnRH neurons with the central nervous system, we also determined the degree to which GnRH cells and their processes were innervated by terminals containing either the endogenous opiate, beta-endorphin (BE) or GnRH itself. Sections from the diagonal band of Broca and the preoptic area of adult male and diestrus II female rats were immunocytochemically processed for dual localization of GnRH and BE. GnRH neurons cut through the plane of the nucleus were identified in 1 micron sections. Serial ultrathin sections were made and analyzed for 1) total synaptic input to both cell bodies and dendrites; 2) BE input; and 3) input arising from GnRH itself. We report that GnRH neuronal cell bodies in females received approximately twice the number of synapses as did those of males. The input to the GnRH dendrites, when measured as percent of plasma membrane in synaptic contact, also showed a profound sexual dimorphism with the female having a larger proportion of the dendrite in synaptic apposition. BE innervation contributed to this dimorphism at the level of both the cell body and dendrite. In contrast, the distribution and number of GnRH terminals did not differ between the sexes. In both they were confined to the dendritic arbor. We hypothesize that the capacity of the female rodent GnRH system to show neurogenic derived alterations in GnRH output not seen in the male may be due in part to these anatomical differences.
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Hormona Liberadora de Gonadotropina/metabolismo , Neuronas/ultraestructura , Caracteres Sexuales , Sinapsis/ultraestructura , Animales , Encéfalo/ultraestructura , Membrana Celular/ultraestructura , Dendritas/ultraestructura , Femenino , Inmunohistoquímica , Masculino , Microscopía Electrónica , Ratas , Ratas Endogámicas F344 , betaendorfina/metabolismoRESUMEN
Physiological and pharmacological evidence has suggested that both endogenous opiates and gonadotropin-releasing hormone (GnRH) itself can act centrally to exert a tonic inhibition on gonadotropin secretion via an inhibition of the neurosecretion of GnRH. To determine if the effects of these two peptides might be mediated via a direct synaptic input to the GnRH neuron, we undertook a double label ultrastructural study. We were able to localize in the same tissue section beta-endorphin and GnRH. Analysis of serial sections through GnRH perikarya and dendrites in the male rat diagonal band/preoptic area revealed that almost 10% of the synapses impinging on the GnRH neuron contained beta-endorphin; an additional 10% of the terminals contained GnRH. These data provide anatomical evidence in support of both a direct modulation of GnRH release by opiates and of the presence of an ultrashort feedback loop.
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Endorfinas/metabolismo , Lóbulo Frontal/metabolismo , Sistemas Neurosecretores/metabolismo , Hormonas Liberadoras de Hormona Hipofisaria/metabolismo , Área Preóptica/metabolismo , Animales , Lóbulo Frontal/citología , Inmunohistoquímica , Masculino , Microscopía Electrónica , Sistemas Neurosecretores/anatomía & histología , Área Preóptica/citología , Ratas , Ratas Endogámicas F344RESUMEN
BACKGROUND: Relatively few studies have been made of children with lupus nephritis. The prognosis of children with lupus nephritis is ominous for those with diffuse proliferative glomerulonephritis and active interstitial inflammation. Up to now few studies have been made on this subject. OBJECTIVES: To evaluate the clinical course, histopathology, and prognosis of lupus nephritis in children, to identify the risk factors for renal failure and mortality, and to share our experience in treating lupus nephritis in children. METHODS: Retrospectively, 167 children under 18 years of age with lupus nephritis at Veterans General Hospital-Taipei, Taiwan from 1979 to 1991 were studied. All patients received renal biopsy and follow-up biopsies were performed in 36 children. The clinical and serologic parameters at the time of renal biopsy were recorded. RESULTS: There were 55 (33%) patients with class II, 30 (18%) with class III, 69 (41.3%) with class IV, and 13 (7.8%) with class V nephritis based on initial biopsy. The mean follow-up time was 59 months. Follow-up biopsies were histologically stationary in 29 patients, progressive in five, and regressive in two. The results revealed that those with persistent hypertension, anemia, increased serum creatinine concentration, and decreased creatinine clearance rate at initial biopsy were more prone to develop renal failure. Low titer of CH50 hemolytic assay appeared to be a poor prognostic indicator. The overall renal and patient 5-year survival rates were 93.1% (135/145) and 91.08% (143/157), respectively. They were 87.7% (50/57) and 82% (55/67), respectively, of patients with class IV proliferative glomerulonephritis. CONCLUSIONS: The prognosis of children with class IV nephritis in this study was better than that reported previously. All children surviving without renal failure were maintaining their normal lives with little organ dysfunction. The improved results may be due to earlier renal biopsy for precise histopathologic definition, better supportive care, and selective use of aggressive therapy, including methylprednisolone pulse therapy, intravenous cyclophosphamide, intravenous prostaglandin E1 therapy, high-dose intravenous gammaglobulin therapy, and cyclosporin A for those with high risk factors.
Asunto(s)
Nefritis Lúpica/epidemiología , Adolescente , Biopsia , Niño , Femenino , Estudios de Seguimiento , Humanos , Riñón/patología , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/terapia , Masculino , Pronóstico , Insuficiencia Renal/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Taiwán/epidemiología , Factores de TiempoRESUMEN
UNLABELLED: This study compares the sensitivity of 99mTc-dimercaptosuccinic acid (DMSA) renal SPECT with planar scintigraphy, concluding the importance of 99mTc-DMSA renal SPECT for the early diagnosis of acute pyelonephritis (APN) in patients under 3 yr of age. METHODS: Twenty-seven children under 3 yr of age, with clinical and/or laboratory suspicion of APN, were investigated. All 99mTc-DMSA renal SPECT and planar images and voiding cystoureterogram (VCUG) were obtained within 3 days of hospitalization. RESULTS: In the first examination, renal cortical defects were detected in 23 patients (42 kidneys) with SPECT and in 9 patients (11 kidneys) with planar scintigraphy. One year after treatment, constant renal cortical lesions were observed in 11 patients (14 kidneys) with SPECT and 4 patients (4 kidneys) with planar scintigraphy. The high grades of vesicoureteral reflux (VUR) (grade >or= 3) correlate better with APN diagnosed by SPECT (34 kidneys) than by planar scintigraphy (8 kidneys). Multiple renal cortical defects (number of lesions >or= 4) were only seen in patients under 1.5 yr old and none of those with a negative 99mTc-DMSA renal SPECT had a positive 99mTc-DMSA renal planar scintigraphy at any time. There is a significant difference (p < 0.05) between the diagnostic ability of these two methods of examination. CONCLUSION: Our results suggest that 99mTc-DMSA renal SPECT should be used, where possible, instead of planar DMSA in routine examination of children with clinical suspicion of APN, especially for those under 3 yr of age.