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1.
Sex Dev ; 6(5): 223-30, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22797524

RESUMEN

In an effort to identify novel candidate genes involved in testis determination, we previously used suppression subtraction hybridisation PCR on male and female whole embryonic (12.0-12.5 days post coitum) mouse gonads. One gene to emerge from our screen was Redd1. In the current study, we demonstrate by whole-mount in situ hybridisation that Redd1 is differentially expressed in the developing mouse gonad at the time of sex determination, with higher expression in testis than ovary. Furthermore, Redd1 expression was first detected as Sry expression peaks, immediately prior to morphological sex determination, suggesting a potential role for Redd1 during testis development. To determine the functional importance of this gene during testis development, we generated Redd1-deficient mice. Morphologically, Redd1-deficient mice were indistinguishable from control littermates and showed normal fertility. Our results show that Redd1 alone is not required for testis development or fertility in mice. The lack of a male reproductive phenotype in Redd1 mice may be due to functional compensation by the related gene Redd2.


Asunto(s)
Reproducción/fisiología , Testículo/embriología , Factores de Transcripción/metabolismo , Animales , Biomarcadores/metabolismo , Cruzamientos Genéticos , Embrión de Mamíferos/metabolismo , Desarrollo Embrionario/genética , Femenino , Fertilidad , Feto/embriología , Técnica del Anticuerpo Fluorescente , Regulación del Desarrollo de la Expresión Génica , Masculino , Ratones , Fenotipo , Reacción en Cadena de la Polimerasa , Reproducibilidad de los Resultados , Células de Sertoli/metabolismo , Testículo/citología , Testículo/crecimiento & desarrollo , Testículo/metabolismo , Factores de Transcripción/deficiencia , Factores de Transcripción/genética
2.
Histol Histopathol ; 27(4): 445-57, 2012 04.
Artículo en Inglés | MEDLINE | ID: mdl-22374722

RESUMEN

Germ cells are the only cells in the body capable of transferring an individual's genetic and epigenetic information to the next generation. However, the developmental processes that provide the foundation for male and female germ line development and later gamete production are complex and poorly understood. In mice the primordial germ cells enter the bipotential gonad at E10.5 and, in response to the testicular or ovarian micro-environment, commit to spermatogenesis or oogenesis. This paper reviews progress in understanding the molecular processes underlying the early stages of male and female germ line development.


Asunto(s)
Ciclo Celular/fisiología , Diferenciación Celular/fisiología , Células Germinativas/fisiología , Procesos de Determinación del Sexo/fisiología , Animales , Embrión de Mamíferos , Desarrollo Embrionario , Femenino , Regulación del Desarrollo de la Expresión Génica , Masculino , Meiosis/fisiología , Ratones , Oogénesis/fisiología , Espermatogénesis/fisiología
4.
BMC Dev Biol ; 3: 1, 2003 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-12659663

RESUMEN

BACKGROUND: Specification of primordial germ cells in mice depends on instructive signalling events, which act first to confer germ cell competence on epiblast cells, and second, to impose a germ cell fate upon competent precursors. fragilis, an interferon-inducible gene coding for a transmembrane protein, is the first gene to be implicated in the acquisition of germ cell competence. RESULTS: Here, we describe four additional fragilis-related genes, fragilis2-5, which are clustered within a 68 kb region in the vicinity of the fragilis locus on Chr 7. These genes exist in a number of mammalian species, which in the human are also clustered on the syntenic region on Chr 11. In the mouse, fragilis2 and fragilis3, which are proximate to fragilis, exhibit expression that overlaps with the latter in the region of specification of primordial germ cells. Using single cell analysis, we confirm that all these three fragilis-related genes are predominant in nascent primordial germ cells, as well as in gonadal germ cells. CONCLUSION: The Fragilis family of interferon-inducible genes is tightly associated with germ cell specification in mice. Furthermore, its evolutionary conservation suggests that it probably plays a critical role in all mammals. Detailed analysis of these genes may also elucidate the role of interferons as signalling molecules during development.


Asunto(s)
Células Germinativas/fisiología , Proteínas de la Membrana/fisiología , Alineación de Secuencia , Secuencia de Aminoácidos , Animales , Blastómeros/química , Blastómeros/citología , Blastómeros/fisiología , Bovinos , Embrión de Mamíferos , Desarrollo Embrionario/fisiología , Femenino , Células Germinativas/química , Células Germinativas/crecimiento & desarrollo , Humanos , Proteínas de la Membrana/biosíntesis , Proteínas de la Membrana/genética , Ratones , Datos de Secuencia Molecular , Especificidad de Órganos/genética , Especificidad de Órganos/fisiología , Embarazo , Ratas
5.
J Exp Zool ; 290(6): 624-31, 2001 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-11748611

RESUMEN

In vertebrates, sex is determined by a surprising variety of mechanisms. In many reptiles, the primary testis or ovary-determining trigger is regulated by egg incubation temperature. This temperature dependent sex determining (TSD) mechanism occurs in all crocodilians and marine turtles examined to date and is common in terrestrial turtles and viviparous lizards (Ewert et al. 1994. J Exp Zool 270:3-15; Lang and Andrews. 1994. J Exp Biol 270:28-44; Mrosovsky. 1994. J Exp Zool 270:16-27; Pieau. 1996. Bioessays 18:19-26; Viets et al. 1994. J Exp Zool 270:45-56; Wibbels et al. 1998. J Exp Zool 281:409-416). In contrast, sex in mammals and birds is determined chromosomally (CSD). Despite these differences, morphological development of the gonads in all these vertebrate groups appears to have been conserved through evolution. Therefore, the genetic mechanisms triggering sex determination appear not to have been conserved through evolution, although the basic genetic pathway controlling the morphological differentiation of the gonads appears to have been conserved.


Asunto(s)
Aves/genética , Mamíferos/genética , Reptiles/genética , Cromosomas Sexuales , Procesos de Determinación del Sexo , Diferenciación Sexual/genética , Temperatura , Animales , Evolución Biológica , Aves/crecimiento & desarrollo , Huevos , Regulación del Desarrollo de la Expresión Génica , Gónadas/crecimiento & desarrollo , Mamíferos/crecimiento & desarrollo , Reptiles/crecimiento & desarrollo
6.
Mech Dev ; 94(1-2): 257-60, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10842083

RESUMEN

We have isolated the SOX8 gene from the chicken embryo. This gene shows a high degree of sequence homology to SOX9 and SOX10. Detailed analysis of SOX8 expression by whole-mount in situ shows a dynamic and restricted expression pattern during chick development. SOX8 is expressed in the somitic derivative, the dermomyotome, the developing heart, pancreas, enteric neurone system, limb and the neural tube. This is the first detailed expression analysis of SOX8 in any species


Asunto(s)
Proteínas de Unión al ADN/genética , Regulación del Desarrollo de la Expresión Génica , Factores de Transcripción/genética , Secuencia de Aminoácidos , Animales , Embrión de Pollo , Proteínas de Unión al ADN/metabolismo , Extremidades/embriología , Datos de Secuencia Molecular , Músculo Esquelético/embriología , Páncreas/embriología , Homología de Secuencia de Aminoácido , Factores de Transcripción/metabolismo
7.
Gene ; 241(2): 223-32, 2000 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-10675033

RESUMEN

Sex determination in mammals and birds is chromosomal, while in many reptiles sex determination is temperature dependent. Morphological development of the gonads in these systems is conserved, suggesting that many of the genes involved in gonad development are also conserved. The genes SF1, WT1 and DAX1 play various roles in the mammalian testis-determining pathway. SF1 and WT1 are thought to interact to cause male-specific gene expression during testis development, while DAX1 is believed to inhibit this male-specific gene expression. We have cloned SF1 and DAX1 from the American alligator, a species with temperature-dependent sex determination (TSD). SF1, DAX1 and WT1 are expressed in the urogenital system/gonad throughout the period of alligator gonadogenesis which is temperature sensitive. SF1 appears to be expressed at a higher level in females than in males. This SF1 expression pattern is concordant with the observed pattern during chicken gonadogenesis, but opposite to that observed during mouse gonadogenesis. Although the observed sexual dimorphism of gonadal SF1 expression in alligators and chickens is opposite that observed in the mouse, it is probable that SF1 is involved in control of gonadal steroidogenesis in all these vertebrates. DAX1 and WT1 are both expressed during stages 22-25 of both males and females. However, there appear to be no sex differences in the expression patterns of these genes. We conclude that DAX1, WT1 and SF1 may be involved in gonadal development of the alligator. These genes may form part of a gonadal-development pathway which has been conserved through vertebrate evolution.


Asunto(s)
Caimanes y Cocodrilos/genética , Ovario/embriología , Proteínas Represoras , Procesos de Determinación del Sexo , Testículo/embriología , Caimanes y Cocodrilos/fisiología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Receptor Nuclear Huérfano DAX-1 , ADN , Proteínas de Unión al ADN/genética , Femenino , Factores de Transcripción Fushi Tarazu , Proteínas de Homeodominio , Masculino , Datos de Secuencia Molecular , Receptores Citoplasmáticos y Nucleares , Receptores de Ácido Retinoico/genética , Homología de Secuencia de Aminoácido , Factor Esteroidogénico 1 , Temperatura , Factores de Transcripción/genética , Proteínas WT1
8.
J Mol Endocrinol ; 24(1): 23-32, 2000 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10656994

RESUMEN

DAX1 is an unusual member of the orphan nuclear receptor family of transcription factors. Mutations in human DAX1 cause X-linked adrenal hypoplasia congenita, while abnormal duplication of the gene is responsible for male-to-female dosage-sensitive sex reversal. Based on these and other observations, DAX1 is thought to play a role in adrenal and gonadal development in mammals. As DAX1 has not previously been described in any other vertebrate, a putative avian DAX1 clone was isolated from an embryonic chicken (Gallus domesticus) urogenital ridge cDNA library. The expression profile of this cDNA was then examined during gonadogenesis. The clone included the conserved 3' ligand-binding motif identified in humans and mice but the 5' region lacked the repeat motif thought to specify a DNA-binding domain in mammals. Southern blot analysis and fluorescence in situ hybridisation mapping showed that the gene is autosomal, located on chromosome 1q. Sequence comparisons showed that the putative chicken DAX1 protein has 63 and 60% identity with the human and mouse proteins respectively over the region of the conserved ligand-binding domain. However, stronger identity (74%) exists with a putative alligator DAX1 sequence over the same region. Northern blotting detected a single 1.4 kb transcript in late embryonic chicken gonads, while RNase protection assays revealed expression in the embryonic gonads of both sexes during the period of sexual differentiation. Expression increased in both sexes during gonadogenesis, but was higher in females than in males. This is the first description of a DAX1 homologue in a non-mammalian vertebrate.


Asunto(s)
Proteínas de Unión al ADN/genética , Receptores de Ácido Retinoico/genética , Proteínas Represoras , Factores de Transcripción/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Southern Blotting , Embrión de Pollo , Clonación Molecular , Receptor Nuclear Huérfano DAX-1 , ADN Complementario , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , Datos de Secuencia Molecular , Homología de Secuencia de Aminoácido , Procesos de Determinación del Sexo , Sistema Urogenital/metabolismo
10.
Dev Dyn ; 214(3): 171-7, 1999 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10090144

RESUMEN

In mammals, birds and reptiles the morphological development of the gonads appear to be conserved. This conservation is evident despite the different sex determining switches employed by these vertebrate groups. Mammals exhibit chromosomal sex determination (CSD) where the key sex determining switch is the Y-linked gene, SRY. Although SRY is the trigger for testis determination in mammals, it is not conserved in other vertebrate groups. However, a gene closely related to SRY, the highly conserved transcription factor, SOX9, plays an important role in the testis pathway of mammals and birds. In contrast to the CSD mechanism evident in mammals and birds, many reptiles exhibit temperature dependent sex determination (TSD) where the egg incubation temperature triggers sex determination. Here we examine the expression of SOX9 during gonadogenesis in the American alligator, (Alligator mississippiensis), a reptile that exhibits TSD. Alligator SOX9 is expressed in the embryonic testis but not in the ovary. However, the timing of SOX9 upregulation in the developing testis is not consistent with a role for this gene in the early stages of alligator sex determination. Since SOX9 upregulation in male embryos coincides with the structural organisation of the testis, SOX9 may operate farther downstream in the vertebrate sex differentiation pathway than previously postulated.


Asunto(s)
Caimanes y Cocodrilos/embriología , Proteínas del Grupo de Alta Movilidad/genética , Procesos de Determinación del Sexo , Factores de Transcripción/genética , Regulación hacia Arriba , Caimanes y Cocodrilos/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , ADN Complementario , Femenino , Humanos , Masculino , Datos de Secuencia Molecular , Factor de Transcripción SOX9 , Temperatura
11.
Dev Dyn ; 216(4-5): 411-9, 1999 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10633860

RESUMEN

Gonadal morphogenesis is very similar among mammals, birds, and reptiles. Despite this similarity, each group utilises quite different genetic triggers for sex determination. In mammals, testis development is initiated by action of the Y-chromosome gene SRY. Current evidence suggests that SRY may act together with a related gene, SOX9, to activate another gene(s) in the pathway of testicular differentiation. A downstream candidate for regulation by SRY and SOX9 is AMH. In mouse, Sox9 is expressed in the Sertoli cells of the embryonic testis and it precedes the onset of Amh expression. During mouse gonadogenesis, Amh is confined to the embryonic testis, although it later shows postnatal expression in the ovary. Reptiles such as the American alligator, which exhibit temperature-dependent sex determination (TSD) do not have dimorphic sex chromosomes and apparently no SRY orthologue. SOX9 is expressed during testis differentiation in the alligator; however, it appears to be expressed too late to cause testis determination. Here we describe the cloning and expression of the alligator AMH gene and show that AMH expression precedes SOX9 expression during testis differentiation. This is the opposite to that observed in the mouse where SOX9 precedes AMH expression. The data presented here, as well as findings from recent expression studies in the chick, suggest that AMH expression is not regulated by SOX9 in the non-mammalian vertebrates.


Asunto(s)
Caimanes y Cocodrilos/embriología , Caimanes y Cocodrilos/genética , Regulación del Desarrollo de la Expresión Génica , Glicoproteínas , Inhibidores de Crecimiento/genética , Proteínas del Grupo de Alta Movilidad/genética , Morfogénesis/fisiología , Procesos de Determinación del Sexo , Hormonas Testiculares/genética , Factores de Transcripción/genética , Secuencia de Aminoácidos , Animales , Hormona Antimülleriana , Secuencia de Bases , Pollos , Femenino , Inhibidores de Crecimiento/química , Humanos , Masculino , Ratones , Datos de Secuencia Molecular , Conductos Paramesonéfricos/embriología , Factor de Transcripción SOX9 , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Temperatura , Hormonas Testiculares/química , Testículo/embriología
12.
Mol Biol Evol ; 13(6): 798-808, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8754216

RESUMEN

The platypus mitochondrial control region has been cloned and sequenced. Comparative analysis of this sequence with the published control region sequences of several other mammalian species has identified regions of sequence consensus that are conserved throughout the Mammalia. Regions predicted to form thermodynamically stable secondary structures in the platypus are also homologous to such putative structures in other species. In addition to these conserved structures, the platypus mitochondrial control region also contains a number of unusual features, including two regions of repetitive sequence, one of which gives rise to pronounced length variation between animals. Possible functions for the conserved structures and a mechanism for the generation of the control region length variation are proposed with respect to our current understanding of mitochondrial replication and transcription.


Asunto(s)
ADN Mitocondrial/genética , Evolución Molecular , Mamíferos/genética , Secuencias Reguladoras de Ácidos Nucleicos , Animales , Secuencia de Bases , Bovinos , ADN Mitocondrial/química , Delfines/genética , Mamíferos/clasificación , Ratones , Datos de Secuencia Molecular , Conformación de Ácido Nucleico , Zarigüeyas/genética , Ornitorrinco/genética , Primates/genética , Conejos , Ratas , Phocidae/genética , Alineación de Secuencia , Homología de Secuencia de Ácido Nucleico , Especificidad de la Especie
13.
Ugeskr Laeger ; 157(3): 291-4, 1995 Jan 16.
Artículo en Danés | MEDLINE | ID: mdl-7846777

RESUMEN

A diet rich in fat may be an important precipitating factor of obesity, but studies on this relation have been hampered by the lack of an objective method to assess habitual dietary fat content. We measured 24-h fat oxidation in a respiration chamber in 38 overwight or obese and 35 nonobese women, and used it as an estimate of habitual dietary fat energy (%). After adjustment for confounders, obese women had higher oxidative fat energy than nonobese women [40.2% (37.8-42.6) vs. 36.0% (33.6-38.5), p < 0.02]. Adjusted oxidative fat energy (%) increased with increasing size of fat mass, and this relation suggest that a 10-kg change in fat mass may be caused by a change in dietary fat energy of > or = 1.6%. This objective assessment supports the contention that obese subjects consume a diet with a higher fat content than nonobese individuals, and the high-fat diet may have causal importance for the development and maintenance of obesity.


Asunto(s)
Grasas de la Dieta/administración & dosificación , Conducta Alimentaria , Metabolismo de los Lípidos , Obesidad/metabolismo , Adulto , Calorimetría Indirecta , Ritmo Circadiano , Metabolismo Energético , Femenino , Humanos , Obesidad/etiología , Oxidación-Reducción
14.
Clin Sci (Lond) ; 87(4): 407-13, 1994 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-7834992

RESUMEN

1. Both increased and decreased sensitivity to insulin has been proposed to precede the development of obesity. Therefore, insulin sensitivity was measured during a 2 h hyperinsulinaemia (100 m-units min-1 m-2) euglycaemic (4.5 mmol/l) glucose clamp combined with indirect calorimetry in nine weight-stable post-obese women and in nine matched control women preceded by 12 h fasting after 48 h on a standardized diet. 2. Both glucose disposal rate (post-obese women, 9.5 +/- 2.2 mg min-1 kg-1, control women, 11.2 +/- 1.4 mg min-1 kg-1, not significant) and glucose oxidation (3.6 +/- 0.5 mg min-1 kg-1 versus 4.0 +/- 0.7 mg min-1 kg-1, not significant) were similar in the two groups during the last 30 min of the clamp. Lipid oxidation also decreased similarly during the clamp in the post-obese women (from 30.4 +/- 12 to 2.0 +/- 7 J min-1 kg-1) and in the control women (from 33.6 +/- 11 to 5.4 +/- 8 J min-1 kg-1, not significant). Basal plasma concentrations of free fatty acids were similar, but at the end of the clamp free fatty acids were lower in the post-obese women than in the control women (139 +/- 19 and 276 +/- 48 mumol/l, P = 0.02). 3. We conclude that the insulin sensitivity of glucose metabolism is unaltered in the post-obese state. The study, however, points to an increased antilipolytic insulin action in post-obese subjects, which may favour fat storage and lower lipid oxidation rate postprandially.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Glucosa/metabolismo , Insulina/fisiología , Obesidad/metabolismo , Adulto , Glucemia/metabolismo , Peso Corporal , Péptido C/sangre , Metabolismo Energético/fisiología , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Insulina/sangre , Obesidad/dietoterapia , Obesidad/genética , Oxidación-Reducción
15.
J Mol Evol ; 39(2): 200-5, 1994 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7932783

RESUMEN

The vertebrate mitochondrial genome is highly conserved in size and gene content. Among the chordates there appears to be one basic gene arrangement, but rearrangements in the mitochondrial gene order of the avian lineages have indicated that the mitochondrial genome may be more variable than once thought. Different gene orders in marsupials and eutherian mammals leave the ancestral mammalian order in some doubt. We have investigated the mitochondrial gene order in the platypus (Ornithorhynchus anatinus), a representative of the third major group of mammals, to determine which mitochondrial gene arrangement is ancestral in mammals. We have found that the platypus mtDNA conforms to the basic chordate gene arrangement, common to fish, amphibians, and eutherian mammals, indicating that this arrangement was the original mammalian arrangement, and that the unusual rearrangements observed in the avians and marsupials are probably lineage-specific.


Asunto(s)
ADN Mitocondrial/genética , Ornitorrinco/genética , Animales , Secuencia de Bases , Evolución Biológica , Southern Blotting , ADN Complementario , Mitocondrias Cardíacas/genética , Mitocondrias Hepáticas/genética , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Alineación de Secuencia
16.
Nurs Manage ; 25(3): 44-6, 1994 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8134040

RESUMEN

A Quality Assessment/Improvement/Competency Model, developed at Norwalk Hospital, provides objective data which fulfills Joint Commission QA/QI requirements. Simultaneously, this monitoring system provides for evaluation of clinical competence.


Asunto(s)
Competencia Clínica , Modelos de Enfermería , Personal de Enfermería en Hospital/normas , Garantía de la Calidad de Atención de Salud , Evaluación del Rendimiento de Empleados , Humanos , Joint Commission on Accreditation of Healthcare Organizations
17.
Am J Clin Nutr ; 59(2): 350-5, 1994 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-7993398

RESUMEN

Expansion of the fat stores has been proposed as a prerequisite for increasing fat oxidation in response to a high-fat diet in individuals with a predisposition to obesity. In a cross-sectional design we measured 24-h substrate oxidations on a standardized diet in 38 overweight or obese and 35 nonobese women. Fat oxidation (g/d) was mainly a function of total energy requirements (r = 0.71, P < 0.0001). To account for this we used for further analysis oxidative fat energy (%), a counterpart to dietary fat energy (%). After differences in fat energy of consumed food (%), age, and 24-h energy balance were adjusted for, obese women had higher oxidative fat energy than did nonobese women [40.2% (37.8-42.6) vs 36.0% (33.6-38.5), P < 0.02]. Adjusted oxidative fat energy (%) increased with increasing size of fat mass (r = 0.31, P < 0.01). This relation suggests that a 10-kg change in fat mass may be caused by a change in dietary fat energy of > or = 1.6% (0.4-2.7%). The study supports the concept that in susceptible individuals the expansion of fat stores is a prerequisite to increase the oxidative fat energy to an amount commensurate with a high percentage of dietary fat energy.


Asunto(s)
Grasas de la Dieta/metabolismo , Obesidad/metabolismo , Tejido Adiposo , Adulto , Análisis de Varianza , Composición Corporal , Estudios Transversales , Carbohidratos de la Dieta/metabolismo , Grasas de la Dieta/administración & dosificación , Ingestión de Energía , Metabolismo Energético , Femenino , Humanos , Oxidación-Reducción , Premenopausia , Análisis de Regresión
18.
Clin Sci (Lond) ; 85(5): 563-8, 1993 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8287644

RESUMEN

1. We investigated the relationship between circulating tumour necrosis factor-alpha concentrations, resting energy expenditure, cachexia and altered intermediary metabolism in patients with cystic fibrosis and chronic pulmonary infection. 2. Twenty adult patients with cystic fibrosis and chronic bronchial sepsis covering a spectrum of severity of lung disease (forced expiratory volume in 1 s 30-100% of predicted) were compared with 10 age matched, healthy, non-cystic fibrosis subjects. 3. Circulating tumour necrosis factor-alpha, C-reactive protein and neutrophil elastase-alpha 1-antiproteinase complex concentrations were determined simultaneously with glycerol, non-esterified fatty acids, catecholamines, anthropometric indices and resting energy expenditure (ventilated hood method). 4. Weight, body mass index and arm muscle mass were reduced in patients with cystic fibrosis compared with healthy control subjects (P < 0.01), whereas mean resting energy expenditure was increased [121 versus 101% predicted, mean difference 19.2% (95% confidence interval 11.0-27.4%), P < 0.001]. Circulating concentrations of glycerol (P < 0.01), non-esterified fatty acids (P < 0.01), adrenaline (P < 0.05), tumour necrosis factor-alpha, C-reactive protein and neutrophil elastase-alpha 1-antiproteinase complex (P < 0.01) were increased in patients compared with control subjects [tumour necrosis factor-alpha 96.9 versus 24.7 pg/ml, mean difference 72.2 pg/ml [95% confidence interval 27.7-116.7 pg/ml), P < 0.001]. Resting energy expenditure was significantly related to tumour necrosis factor-alpha levels and forced expiratory volume in 1 s. 5. In patients with cystic fibrosis and chronic pulmonary sepsis changes in resting energy expenditure, body composition and intermediary metabolism are consistent with the systemic effects of the host inflammatory response, which may be responsible for cachexia in adult patients. In particular these changes are consistent with the action of tumour necrosis factor-alpha, which was detected in the circulation during a period of apparent clinical stability.


Asunto(s)
Caquexia/metabolismo , Fibrosis Quística/metabolismo , Metabolismo Energético , Elastasa de Leucocito , Factor de Necrosis Tumoral alfa/metabolismo , Adulto , Proteína C-Reactiva/metabolismo , Catecolaminas/metabolismo , Femenino , Humanos , Masculino , Elastasa Pancreática/metabolismo , Infecciones del Sistema Respiratorio/metabolismo , alfa 1-Antitripsina/metabolismo
19.
J Cardiovasc Pharmacol ; 13 Suppl 6: S43-6, 1989.
Artículo en Inglés | MEDLINE | ID: mdl-2473348

RESUMEN

The natriuretic, diuretic, and hypotensive responses to infused atrial natriuretic peptide (ANP) were measured in rats 4 weeks after myocardial infarction induced by coronary artery ligation. Rat [1-28]-ANP was infused intravenously in doses of 0.1, 0.3, and 1.0 microgram/kg/min for 30 min each under pentobarbital anesthesia. There was a marked natriuresis, diuresis, and fall in blood pressure in rats with infarction but each response was significantly attenuated when compared with sham-operated controls (ANOVA: p less than 0.01, p less than 0.05, and p less than 0.01, respectively). Urinary cyclic guanosine monophosphate (cGMP) excretion in rats with infarction was higher than that of controls but rose to the same absolute level in both groups in response to ANP infusion (0.3 microgram/kg/min). Reduced ANP responsiveness may result from impaired postreceptor mechanisms or from physiological antagonism by angiotensin II. Reduced ANP responsiveness may partly explain impaired salt handling in heart failure.


Asunto(s)
Factor Natriurético Atrial/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Animales , Factor Natriurético Atrial/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Enfermedad Crónica , Vasos Coronarios/fisiología , GMP Cíclico/orina , Femenino , Insuficiencia Cardíaca/fisiopatología , Infarto del Miocardio/fisiopatología , Ratas , Ratas Endogámicas , Sodio/orina , Urodinámica/efectos de los fármacos
20.
Respir Physiol ; 72(1): 123-30, 1988 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-3363231

RESUMEN

In an attempt to identify a cause for the alteration in breathing pattern seen when conventional respiratory apparatus is applied to the face, we have studied the effects of causing the subject to focus attention on breathing by counting breaths in threes for 5 min. We used the respiratory inductance plethysmograph in 18 naive subjects who were unaware that their breathing was being measured. In the control periods, distraction was provided by a recorded story played through head-phones. The experiment was repeated with the rim of a facemask applied to the face. Focusing attention on breathing caused a prolongation of inspiration at a constant mean inspiratory flow, and lengthening of expiration. Tidal volume but not ventilation was increased. The facemask rim caused no significant change. It is concluded that conscious awareness of breathing could account for a major part of the effect of conventional respiratory apparatus.


Asunto(s)
Máscaras , Respiración , Pruebas de Función Respiratoria/instrumentación , Adolescente , Adulto , Resistencia de las Vías Respiratorias , Atención , Cara , Humanos , Masculino , Persona de Mediana Edad , Volumen de Ventilación Pulmonar , Factores de Tiempo
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