RESUMO
BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is associated with a high mortality rate due to the development of life-threatening, metastatic cutaneous squamous cell carcinoma (cSCC). Elevated transforming growth factor-beta (TGF-ß) signalling is implicated in cSCC development and progression in patients with RDEB. OBJECTIVES: To determine the effect of exogenous and endogenous TGF-ß signalling in RDEB cSCC with a view to assessing the potential of targeting TGF-ß signalling for RDEB cSCC therapy. METHODS: A panel of 11 patient-derived RDEB cSCC primary tumour keratinocyte cell lines (SCCRDEBs) were tested for their signalling and proliferation responses to exogenous TGF-ß. Their responses to TGF-ß receptor type-1 (TGFBR1) kinase inhibitors [SB-431542 and AZ12601011 (AZA01)] were tested using in vitro proliferation, clonogenicity, migration and three-dimensional invasion assays, and in vivo tumour xenograft assays. RESULTS: All SCCRDEBs responded to exogenous TGF-ß by activation of canonical SMAD signalling and proliferative arrest. Blocking endogenous signalling by treatment with SB-431542 and AZ12601011 significantly inhibited proliferation (seven of 11), clonogenicity (six of 11), migration (eight of 11) and invasion (six of 11) of SCCRDEBs. However, these TGFBR1 kinase inhibitors also promoted proliferation and clonogenicity in two of 11 SCCRDEB cell lines. Pretreatment of in vitro TGFBR1-addicted SCCRDEB70 cells with SB-431542 enhanced overall survival and reduced tumour volume in subcutaneous xenografts but had no effect on nonaddicted SCCRDEB2 cells in these assays. CONCLUSIONS: Targeting TGFBR1 kinase activity may have therapeutic benefit in the majority of RDEB cSCCs. However, the potential tumour suppressive role of TGF-ß signalling in a subset of RDEB cSCCs necessitates biomarker identification to enable patient stratification before clinical intervention.
Assuntos
Carcinoma de Células Escamosas , Epidermólise Bolhosa Distrófica , Neoplasias Cutâneas , Humanos , Fator de Crescimento Transformador beta , Fatores de Crescimento TransformadoresRESUMO
The Indo-Gangetic aquifer is one of the world's most important transboundary water resources, and the most heavily exploited aquifer in the world. To better understand the aquifer system, typologies have been characterized for the aquifer, which integrate existing datasets across the Indo-Gangetic catchment basin at a transboundary scale for the first time, and provide an alternative conceptualization of this aquifer system. Traditionally considered and mapped as a single homogenous aquifer of comparable aquifer properties and groundwater resource at a transboundary scale, the typologies illuminate significant spatial differences in recharge, permeability, storage, and groundwater chemistry across the aquifer system at this transboundary scale. These changes are shown to be systematic, concurrent with large-scale changes in sedimentology of the Pleistocene and Holocene alluvial aquifer, climate, and recent irrigation practices. Seven typologies of the aquifer are presented, each having a distinct set of challenges and opportunities for groundwater development and a different resilience to abstraction and climate change. The seven typologies are: (1) the piedmont margin, (2) the Upper Indus and Upper-Mid Ganges, (3) the Lower Ganges and Mid Brahmaputra, (4) the fluvially influenced deltaic area of the Bengal Basin, (5) the Middle Indus and Upper Ganges, (6) the Lower Indus, and (7) the marine-influenced deltaic areas.
L'aquifère de l'Indus et du Gange est une des ressources en eau transfrontalière la plus importante au monde et un des aquifères le plus exploité au monde. Pour mieux comprendre le système aquifère, des typologies ont été caractérisées pour cet aquifère ; elles intègrent pour la première fois un jeu de données disponibles sur l'ensemble du bassin de l'Indus et du Gange à une échelle transfrontalière, et apportent une conceptualisation alternative de ce système aquifère. Traditionnellement considéré et cartographié comme un simple aquifère homogène aux propriétés aquifères similaires et comme une ressource d'eau souterraine à l'échelle transfrontalière, les typologies mettent en évidence des différences significatives spatiales de la recharge, de la perméabilité, de la capacité de stockage et de la chimie des eaux souterraines sur l'ensemble du système aquifère à une échelle transfrontalière. Ces changements sont systématiques coïncidant aux changements à large échelle de la sédimentologie de l'aquifère alluvial du Pléistocène et de l'Holocène, du climat et des pratiques récentes d'irrigation. Sept typologies de l'aquifère sont présentées, chacune ayant un ensemble distinct de défis et d'opportunités pour le développement des eaux souterraines et une résilience différente à l'exploitation et au changement climatique. Les sept typologies sont: (1) la marge de piedmont, (2) Le haut Indus et le Ganges moyen supérieur, (3) le Ganges inférieur et le Brahmapoutre moyen, (4) la zone deltaïque du bassin du Bengale sous influence fluviale, (5) l'Indus moyen et le Ganges supérieur, (6) l'Indus inférieur, et (7) la zone deltaïque sous influence marine.
El acuífero Indo-Gangético es uno de los recursos hídricos transfronterizos más importantes y el acuífero más explotado del mundo. Para comprender mejor el sistema acuífero, por primera vez se han caracterizado tipologías para el acuífero, integrando los conjuntos de datos existentes a través de la cuenca hidrográfica Indo-Ganges a una escala transfronteriza, y proporcionando una conceptualización alternativa de este sistema acuífero. Tradicionalmente consideradas y cartografiadas como un solo acuífero homogéneo de propiedades acuíferas y recursos de agua subterránea comparables a escala transfronteriza, las tipologías iluminan diferencias espaciales significativas en la recarga, permeabilidad, almacenamiento y química del agua subterránea a través del sistema acuífero a esta escala transfronteriza. Estos cambios son mostrados por ser sistemáticos, coincidentes con cambios en gran escala en la sedimentología del acuífero aluvial del Pleistoceno y del Holoceno, en el clima y en las prácticas recientes de riego. Se presentan siete tipologías del acuífero, cada una con un conjunto distinto de desafíos y oportunidades para el desarrollo del agua subterránea y una diferente resiliencia a la extracción y al cambio climático. Las siete tipologías son: (1) el margen del piedemonte, (2) el Indus superior y el Ganges superior-medio, (3) el Ganges inferior y el Brahmaputra medio, (4) el área deltaica fluvialmente influenciada de la cuenca de Bengala, (5) el Ganges superior, (6) el Indo Inferior, y (7) las áreas deltaicas con influencia marina.
O aquífero do Indo-Gangético é um dos recursos hídricos transfronteiriços mais importantes do mundo, e o mais explorado. Para melhor entender o sistema aquífero, tipologias foram caracterizadas para o aquífero, que integram pela primeira vez bancos de dados existentes sobre a bacia de abastecimento Indo-Gangética em uma escala transfornteiriça, e fornecem uma conceptualização alternativa desse sistema aquífero. Tradicionalmente considerado e mapeado como um aquífero homogêneo de propriedades aquíferas comparáveis e recursos subterrâneos em escala transfronteiriça, as tipologias elucidam diferenças espaciais significantes na recarga, permeabilidade, armazenamento, e química das águas subterrâneas pelo aquífero nessa escala transfronteiriça. Essas mudanças aparentam ser sistemáticas, concorrentes com mudanças em larga escala na sedimentologia do aquífero aluvial do Pleistoceno e Holoceno, clima e práticas recentes de irrigação. Sete tipologias do aquífero são apresentadas, cada uma tendo conjuntos de desafios e oportunidades distintos para o desenvolvimento das águas subterrâneas e uma resiliência diferente nas mudanças de extração e clima. As sete tipologias são: (1) a margem piemonte, (2) O Alto Indo e o Alto-médio Ganges, (3) O Baixo Ganges e o Médio Brahmaputra, (4) a área deltaica influenciada fluvialmente da Bacia de Bengala, (5) o Médio Indo e o Alto Ganges, (6) o Baixo Indo, e (7) as áreas deltaicas com influencia marinha.
RESUMO
Three travel cost models are used to estimate non-fishing recreation demand at the Snake River reservoirs recreation area in eastern Washington. The opportunity cost of time is specified in the "traditional" and McConnell-Strand models as a fraction of the exogenous market wage rate and in the two-step decision model as a function of socioeconomic attributes of the recreationists. Benefits per person per trip were $90, $35, and $46 respectively, for the three models. Boaters visit the site more than three times as often as non-boaters resulting in higher annual benefits for boaters.
Assuntos
Conservação dos Recursos Naturais , Recreação , Modelos Teóricos , Rios , WashingtonRESUMO
Calpain (a Ca(2+)-dependent protease) is present in many cell types. Because it is present in the cytosol, the potential exists that it may regulate critical intracellular events by inducing crucial proteolytic cleavages. However, the concentrations of Ca2+ required to activate calpain are higher than those attained in the cytoplasm of most cells. Thus, the physiological importance of calpain and the mechanisms involved in its activation have remained elusive. In this study, we show that calpain rapidly moved to a peripheral location upon the addition of an agonist to suspensions of platelets, but it remained unactivated. We provide three lines of evidence that calpain was subsequently activated by a mechanism that required the binding of an adhesive ligand to the major platelet integrin, glycoprotein (GP) IIb-IIIa: calpain activation was prevented by RGDS, a tetrapeptide that inhibits the binding of adhesive ligand to GP IIb-IIIa; it was also prevented by monoclonal antibodies that inhibit adhesive ligand binding to GP IIb-IIIa; and its activation was markedly reduced in platelets from patients whose platelets have greatly reduced levels of functional GP IIb-IIIa. Thus, in platelets, binding of the extracellular domain of GP IIb-IIIa to its adhesive ligand can initiate a transmembrane signal that activates intracellular calpain. Because calpain is present in focal contacts of adherent cells, the interaction of integrins with adhesive ligands in the extracellular matrix may regulate activation of calpain in other cell types as well.
Assuntos
Plaquetas/metabolismo , Calpaína/sangue , Oligopeptídeos/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Glicoproteínas da Membrana de Plaquetas/metabolismo , Adulto , Plaquetas/enzimologia , Ativação Enzimática , Humanos , Técnicas In Vitro , Cinética , Ligantes , Oligopeptídeos/síntese química , Agregação Plaquetária/efeitos dos fármacos , Trombastenia/sangue , Trombastenia/enzimologiaRESUMO
We assessed the utility of online fluorescence spectroscopy for the real-time evaluation of the microbial quality of untreated drinking water. Online fluorimeters were installed on the raw water intake at four groundwater-derived UK public water supplies alongside existing turbidity sensors that are used to forewarn of the presence of microbial contamination in the water industry. The fluorimeters targeted fluorescent dissolved organic matter (DOM) peaks at excitation/emission wavelengths of 280/365â¯nm (tryptophan-like fluorescence, TLF) and 280/450â¯nm (humic-like fluorescence, HLF). Discrete samples were collected for Escherichia coli, total bacterial cell counts by flow cytometry, and laboratory-based fluorescence and absorbance. Both TLF and HLF were strongly correlated with E. coli (ρâ¯=â¯0.71-0.77) and total bacterial cell concentrations (ρâ¯=â¯0.73-0.76), whereas the correlations between turbidity and E. coli (ρâ¯=â¯0.48) and total bacterial cell counts (ρâ¯=â¯0.40) were much weaker. No clear TLF peak was observed at the sites and all apparent TLF was considered to be optical bleed-through from the neighbouring HLF peak. Therefore, a HLF fluorimeter alone would be sufficient to evaluate the microbial water quality at these sources. Fluorescent DOM was also influenced by site operations such as pump start-up and the precipitation of cations on the sensor windows. Online fluorescent DOM sensors are a better indicator of the microbial quality of untreated drinking water than turbidity and they have wide-ranging potential applications within the water industry.
Assuntos
Água Potável/microbiologia , Espectrometria de Fluorescência/métodos , Qualidade da Água , Água Potável/química , Inglaterra , Escherichia coli , Citometria de Fluxo , Fluorescência , Água Subterrânea/microbiologia , Triptofano/química , Microbiologia da Água , Abastecimento de ÁguaRESUMO
Two daughters of a propositus with documented McArdle's disease were shown by enzyme assay, gel electrophoresis, and immunoblotting to be partially deficient in skeletal muscle phosphorylase and, presumably, heterozygous for the trait. Both exhibited only the adult form of the skeletal muscle isozyme. By 31P-nuclear magnetic resonance, both heterozygotes showed a greater production of acid during fully aerobic exercise than when blood flow was occluded in ischemic exercise. This pattern is in contrast to that of control subjects, where there is significantly greater acid production in ischemic versus aerobic exercise, and distinct from that of phosphorylase-negative patients in which no acid is produced in either circumstance. We suggest that these heterozygotes may have adapted to their diminished phosphorylase by enhancing utilization of plasma glucose. If so, this mechanism could account for the observation that most of the symptoms of McArdle's disease are often manifest only in adulthood. These studies also show that although there are very high concentrations of phosphorylase in skeletal muscle (approximately 2% of the soluble protein), such a high level is essential for normal muscle glycogenolysis.
Assuntos
Triagem de Portadores Genéticos , Doença de Depósito de Glicogênio Tipo V/genética , Doença de Depósito de Glicogênio/genética , Espectroscopia de Ressonância Magnética , Adulto , Biópsia , Creatina Quinase/análise , Eletromiografia , Eletroforese em Gel de Poliacrilamida , Feminino , Doença de Depósito de Glicogênio Tipo V/metabolismo , Humanos , Isoenzimas , Pessoa de Meia-Idade , Contração Muscular , Músculos/enzimologia , Esforço FísicoRESUMO
Groundwater-level fluctuations represent hydraulic responses to changes in groundwater storage due to aquifer recharge and drainage as well as to changes in stress that include water mass loading and unloading above the aquifer surface. The latter 'poroelastic' response of confined aquifers is a well-established phenomenon which has been demonstrated in diverse hydrogeological environments but is frequently ignored in assessments of groundwater resources. Here we present high-frequency groundwater measurements over a twelve-month period from the tropical, fluvio-deltaic Bengal Aquifer System (BAS), the largest aquifer in south Asia. The groundwater level fluctuations are dominated by the aquifer poroelastic response to changes in terrestrial water loading by processes acting over periods ranging from hours to months; the effects of groundwater flow are subordinate. Our measurements represent the first direct, quantitative identification of loading effects on groundwater levels in the BAS. Our analysis highlights the potential limitations of hydrogeological analyses which ignore loading effects in this environment. We also demonstrate the potential for employing poroelastic responses in the BAS and across other tropical fluvio-deltaic regions as a direct, in-situ measure of changes in terrestrial water storage to complement analyses from the Gravity and Climate Experiment (GRACE) mission but at much higher resolution.
RESUMO
An asymptomatic child with antenatally diagnosed globoid cell leukodystrophy was found to have electrodiagnostic evidence of peripheral neuropathy at 7 weeks of age. The earliest prior such evidence in the literature was in a 6-month-old-child. Thus, peripheral neuropathy can be both the initial manifestation and a very early finding in Krabbe's disease.
Assuntos
Leucodistrofia de Células Globoides/diagnóstico , Doenças do Sistema Nervoso Periférico/diagnóstico , Eletrodiagnóstico , Feminino , Humanos , Lactente , Gravidez , Diagnóstico Pré-NatalRESUMO
Oxygen derived free radicals are generated by osteoclasts. In a novel culture system, isolated rat osteoclasts were stained when nitroblue tetrazolium (NBT) was reduced by cellular oxidants to formazan, an insoluble precipitate. Superoxide dismutase (SOD) inhibited the accumulation of formazan by the isolated osteoclasts. Osteoclasts in mouse calvarial organ cultures also reduced NBT to formazan. The reaction products were localized to the area of the osteoclast-bone interface. At the light microscopic level, the formazan granules appeared to be concentrated within the cytoplasm. Formazan accumulation was significantly inhibited by calcitonin (hCT). The inhibition of NBT reduction by SOD indicates that the isolated osteoclasts were capable of producing superoxide. The localization of the formazan granules between the external osteoclastic membrane and the bone, and the inhibition of this reaction during hCT exposure suggests that oxygen derived free radicals may contribute to bone resorption.
Assuntos
Nitroazul de Tetrazólio , Osteoclastos/metabolismo , Superóxidos/metabolismo , Sais de Tetrazólio , Animais , Reabsorção Óssea , Células Cultivadas , Radicais Livres , Osteoblastos/metabolismo , Ratos , Sensibilidade e EspecificidadeRESUMO
Muscle protein degradation has an important role in rate of muscle growth. It has been difficult to develop procedures for measuring rate of muscle protein degradation in living animals, and most studies have used in vitro systems and muscle strips to determine rate of protein degradation. The relationship between results obtained by using muscle strips and rate of muscle protein turnover in living animals is unclear because these strips are in negative nitrogen balance and often develop hypoxic cores. Also, rate of protein degradation is usually estimated by release of labeled amino acids, which reflects an average rate of degradation of all cellular proteins and does not distinguish between rates of degradation of different groups of proteins such as the sarcoplasmic and the myofibrillar proteins in muscle. A number of studies have suggested that the calpain system initiates turnover of myofibrillar proteins, which are the major group of proteins in striated muscle, by making specific cleavages that release thick and thin filaments from the surface of the myofibril and large polypeptide fragments from some of the other myofibrillar proteins. The calpains do not degrade myofibrillar proteins to small peptides or to amino acids, and they cause no bulk degradation of sarcoplasmic proteins. Hence, the calpains are not directly responsible for release of amino acids during muscle protein turnover. Activity of the calpains in living cells is regulated by calpastatin and Ca2+, but the nature of this regulation is still unclear.
Assuntos
Calpaína/fisiologia , Desenvolvimento Muscular , Animais , Microscopia Eletrônica , Proteínas Musculares/metabolismo , Músculos/metabolismo , Músculos/ultraestrutura , Miofibrilas/metabolismoRESUMO
The influence of varying dietary fatty acid ratios on plasma lipids, platelet function and the potential for thrombosis was evaluated in the African green monkey (Cercopithecus aethiops), an animal model widely used in cardiovascular research. Ten adult animals, 5 males and 5 females, at intervals of 2 months, were fed a series of 7 diets with fatty acid ratios (P:S) ranging from 3:1 to 1:4. Platelet aggregation in vitro, plasma levels of beta-thromboglobulin and platelet factor 4, platelet membrane fatty acid composition and plasma lipids including total cholesterol, HDL and LDL were monitored at the end of each dietary period. Platelet hypersensitivity to ADP aggregation (3 and 10 microM) and plasma beta-thromboglobulin were elevated in both males and females when dietary P:S exceeded 1.5:1 (beta-TG = 45 ng/ml) as compared to control diets either reflecting current North American or that recommended as a desirable dietary goal (P:S = 1:1, beta-TG = 10 ng/ml). Diets enriched in saturated fatty acids (P:S = 1:2) also altered platelet function, but the effects were most consistently observed in female animals (beta-TG = 32 ng/ml). Platelet hypersensitivity was lost and beta-TG levels were at baseline when the animals were returned to the control diets. Platelet sensitivity did not correlate with membrane composition which generally reflected dietary composition. Both the saturated and the polyunsaturated fatty acid enriched diets lowered plasma HDL levels, and the saturated fatty acid diets elevated plasma LDL.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Plaquetas/fisiologia , Gorduras na Dieta/farmacologia , Lipídeos/sangue , Animais , Chlorocebus aethiops , Ácidos Graxos/metabolismo , TromboseRESUMO
Squamous cell carcinoma of the ocular conjunctiva is a relatively rare malignancy which is attended by a high rate of local recurrence following simple surgical excision. To date, the management of conjunctival squamous cell cancer has been controversial. From 1950 to 1985, 146 consecutive patients with superficial conjunctival squamous cell cancer were treated at the Queensland Radium Institute. All patients were treated by simple surgical excision of the visible conjunctival lesion followed by adjunctive radiotherapy. Of 140 patients with histologically confirmed squamous cell cancer, 123 were treated with a strontium-90 source, 10 with a radon "ring," and 7 with superficial X ray therapy. Standard policy since 1960 has been to deliver an incident dose of 30 Gy in a single fraction within the first 48 post-operative hours to the surgical bed using a strontium-90 source on a stand-off eye applicator. This report will largely focus on the 123 patients who were treated with a strontium-90 source, of whom 107 received 30 Gy, 14 received 40 Gy (pre 1960) and one patient each received 20 and 25 Gy incident dose. Of 131 evaluable patients, there were only 3 who developed local recurrence. All 3 local recurrences developed in elderly men who had presented with extensive superficial primary tumors. Two of the three recurrences occurred in the two patients who were treated with doses less than 30 Gy. Both early and late radiation-induced complications following ablative surgery and treatment with strontium-90 were very uncommon. Three patients developed unsightly conjunctival telangiectasia, 2 patients developed a persistent scleral ulcer and 2 patients developed clinically significant cataracts. This negligible degree of treatment-related side effects contrasts with the experience of 10 patients who had previously been treated with a radon ring, 8 of whom developed serious complications, although none developed local recurrence. On the basis of our excellent local control rates with minimal morbidity we would continue to advocate the use of simple surgical excision followed by 30 Gy beta radiation from a strontium-90 source as the definitive treatment for superficial conjunctival squamous cell cancer.
Assuntos
Braquiterapia , Carcinoma de Células Escamosas/radioterapia , Neoplasias da Túnica Conjuntiva/radioterapia , Radioisótopos de Estrôncio/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/instrumentação , Braquiterapia/métodos , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada , Neoplasias da Túnica Conjuntiva/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The regulation of glucose metabolism by glucagon and GLP-1 is well established, but novel functions for these and other proglucagon-derived peptides are less well defined. This paper highlights the diversity of both GLP-1 and glucagon activity by studying the tissue distribution of glucagon and GLP-1 receptor gene expression by both Southern blot analysis of RT-PCR products and nuclease protection assays. By Southern blot analysis of RT-PCR products, GLP-1 receptor mRNA was detected in lung, hypothalamus, hippocampus, cerebral cortex, kidney, pancreas, and throughout the gastrointestinal tract. Glucagon receptor expression was detected in liver, kidney, spleen, thymus, adrenal glands, pancreas, cerebral cortex, lung, and throughout the gastrointestinal tract. Nuclease protection assay revealed glucagon receptor expression to be highest in liver and kidney, whereas GLP-1 receptor expression was only detected by protection assay in lung, stomach, and large bowel. Despite previous evidence that other receptors for proglucagon-derived peptides may exist, no evidence of novel receptors or multiple isoforms of the glucagon and GLP-1 receptors was found, indicating that the two cloned receptors may mediate all the effects of proglucagon-derived peptides, or that novel receptors may share less homology with the glucagon and GLP-1 receptors than previously anticipated.
Assuntos
Receptores de Glucagon/genética , Animais , Sequência de Bases , Southern Blotting , Primers do DNA , Sondas de DNA , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hibridização de Ácido Nucleico , Especificidade de Órgãos , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência do Ácido Nucleico , Endonucleases Específicas para DNA e RNA de Cadeia SimplesRESUMO
Changes in the levels of ileal insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) mRNA in the rat following massive small bowel resection (MSBR) have been investigated with a sensitive S1 nuclease assay. IGF-I mRNA levels vary little over 7 days; in contrast IGFBP-3 mRNA levels decreased to one-third 7 h post-MSBR, and remained suppressed for the length of this study. We postulate that decreased ileal synthesis of IGFBP-3 enhances the ability of IGF-I to stimulate the adaptive response.
Assuntos
Proteínas de Transporte/genética , Expressão Gênica , Íleo/metabolismo , Fator de Crescimento Insulin-Like I/genética , Intestino Delgado/cirurgia , RNA Mensageiro/genética , Animais , Proteínas de Transporte/biossíntese , Feminino , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Fator de Crescimento Insulin-Like I/biossíntese , RNA Mensageiro/análise , Ratos , Ratos EndogâmicosRESUMO
The molecular forms of gonadotropin-releasing hormone (GnRH) in brain-pituitary extracts were determined for snook Centropomus undecimalis and black sea bass Centropristis striata. The extracts were analyzed in both isocratic and gradient high performance liquid chromatography (HPLC) programs. Eluted fractions were tested in radioimmunoassays with 4 different antisera made against 3 distinct GnRH peptides. Results show that snook contain 3 forms of GnRH, all of which are present in males and females irrespective of the stage of the reproductive cycle. Larger quantities of these GnRH peptides are present in snook in the nonreproductive phase than in snook in the reproductive phase. One form of snook GnRH is immunologically and chromatographically similar to salmon GnRH, and a second form is similar to chicken GnRH-II. However, the third snook GnRH appears to be distinct from the 7 known forms of the vertebrate hormone. In contrast, sea bass contain only the salmon GnRH-like and chicken GnRH-II-like forms of GnRH and, hence, appear to match the more usual pattern of GnRH peptides in teleosts. We speculate that one of the GnRH genes was duplicated and then altered in a fish ancestral to snook but not sea bass, even though both species of fish are in the recently evolved Perciformes order.
Assuntos
Bass/metabolismo , Química Encefálica , Peixes/metabolismo , Hormônio Liberador de Gonadotropina/química , Hipófise/química , Animais , Cromatografia Líquida de Alta Pressão , Feminino , Hormônio Liberador de Gonadotropina/análise , Masculino , Radioimunoensaio , Especificidade da EspécieRESUMO
RNA, DNA, and NCP content were measured in fast- and slow-twitch skeletal muscle of normal and dystrophic mice (HDM) and their littermates at ages 4 through 29 weeks. In normal and litter mate mice RNA and DNA content were far greater in the soleus than in the gastrocnemius while the RNA/DNA ratio and NCP content were greater in the gastrocnemius. In dystrophic mice, however, the differences between nuleic acid content of the 2 muscles were far less, apparently due to a proportionately higher content in the dystrophic gastrocnemius. Due to a proportionately lower ratio in the gastrocnemius, dystrophic RNA/DNA ratios for the 2 muscles were essentially the same. Age had a marked effect on the nucleic acid content of both muscles in all 3 mice types but to varying degrees. In the soleus, RNA and DNA content rapidly decreased until 9 to 10 weeks of age followed by a gradual decline. Soleus RNA/DNA ratios showed little change with age except in the HDM mice in which there was a significant overall decline. In the gastrocnemius, RNA content followed the same pattern but with a smaller decline in the younger ages. Age had no affect on DNA content in the normal gastrocnemius, but there was significant decline in the HDM gastrocnemius. RNA/DNA gastrocnemius ratios showed marked fluctuations in both normal and dystrophic mice but did not appear to be affected by age.
Assuntos
Músculos/análise , Distrofia Muscular Animal/metabolismo , Ácidos Nucleicos/análise , Fatores Etários , Animais , DNA/análise , Camundongos , Contração Muscular , Proteínas Musculares/análise , RNA/análiseRESUMO
Fifty-nine biopsies of human muscle, 53 of them abnormal, 6 normal, were studied for the histochemical localization of acetylcholinesterase (AChE) using frozen sections and light microscopy. In addition to AChE which was found at the myoneural and myotendon junction, specific staining was found around the periphery of many fibers from normal and abnormal muscles. Moreover, AChE activity was found to be high in the sarcoplasm of more than 10% of the fibers from 28 biopsies of abnormal muscle including cases of hemiplegia, spinal cord injury, denervation and neuropathy, infantile spinal muscle atrophy, Duchenne, limb-girdle and facioscapulohumeral dystrophies, Schwartz-Jampel syndrome and a myasthenic syndrome. Of the muscles from experimental animals examined, only the Rhesus monkey exhibited AChE around the periphery of the fibers, and only the dystrophic chicken and not the dystrophic mouse or hamster, showed extensive sarcoplasmic AChE. Histograms of muscle fiber diameters indicated that AChE in the sarcoplasm was associated with fibers of all sizes, depending on the nature of the disorder examined. Fibers containing AChE were smaller than unstained fibers in dystrophic chicken muscle. The results suggest that in the human, sarcoplasmic AChE is reversibly repressed during muscle maturation and that its mode of regulation by motor neurons is similar to that found in the chicken.
Assuntos
Acetilcolinesterase/metabolismo , Músculos/enzimologia , Doenças Musculares/enzimologia , Doenças do Sistema Nervoso/enzimologia , Adolescente , Adulto , Idoso , Animais , Butirilcolinesterase/metabolismo , Gatos , Galinhas , Cricetinae , Citoplasma/enzimologia , Denervação , Feminino , Feto/enzimologia , Haplorrinos , Humanos , Lactente , Macaca mulatta , Masculino , Camundongos , Pessoa de Meia-Idade , Placa Motora/enzimologia , Distrofias Musculares/enzimologia , SíndromeRESUMO
This study was conducted to determine whether the application of high hydrostatic pressure could modify the enzymatic activity and membrane integrity of lysosomes in muscle. Several combinations of pressure (0-600 MPa) and time (0-300 s) were applied to two types of samples: purified enzymes (cathepsin D and acid phosphatase) in buffer solution and intact muscle (biceps femoris). The enzymes studied showed varying degrees of susceptibility depending on the level of pressure, holding time, and environment. Acid phosphatase activity was minimally affected by pressure in buffer solution, whereas cathepsin D was modulated significantly by the pressure and time applied. The activities of the enzymes extracted from meat increased with pressure. The cytochemical observations showed the presence of primary and secondary lysosomes in muscles. After pressurization, the membrane integrity of the lysosomes was modified. A correlation could be established between lysosomal enzymatic activities and the lysosome membrane breakdown.
Assuntos
Fosfatase Ácida/metabolismo , Catepsina D/metabolismo , Lisossomos/ultraestrutura , Carne , Músculo Esquelético/ultraestrutura , Animais , Bovinos , Feminino , Manipulação de Alimentos , Pressão Hidrostática , Lisossomos/enzimologia , Músculo Esquelético/enzimologiaRESUMO
Exercise-induced weakness (fatiguing) is described in three patients with cervical compressive radiculopathy. In all three cases, the patients had symptoms only while at work, and in two cases, symptoms occurred in life-threatening situations. All patients had seen several physicians with a functional diagnosis being considered in all cases because of symptoms only at work and the absence of objective findings during examination. Precise history and examination techniques led to the correct diagnosis and treatment after appropriate investigation. The fatiguing weakness in our cases is thought to be a manifestation of early or mild neurologic involvement unmasked by exercise, rather than a manifestation of compression or ischemia.
Assuntos
Fadiga/diagnóstico por imagem , Síndromes de Compressão Nervosa/diagnóstico por imagem , Raízes Nervosas Espinhais/diagnóstico por imagem , Adulto , Fadiga/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Esforço Físico , RadiografiaRESUMO
A retrospective study of 42 children with hypertension secondary to renal disease is presented. Thirty-three had scarred kidneys, 5 had renovascular disease, 2 had renal venous thrombosis, 1 had an angiomatous malformation of the upper pole of the kidney, and 1 had glomerulonephritis. Twenty-six children were managed surgically. The etiology, presentation, and management are presented. Follow-up varied from 2 to 14 years and the outcome is discussed.