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1.
Int Urogynecol J ; 26(5): 707-13, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25429825

RESUMO

INTRODUCTION AND HYPOTHESIS: The objective of this study was to quantitatively assess the ability of new MRI-based measurements to differentiate low and high stages of pelvic organ prolapse. New measurements representing pelvic structural characteristics are proposed and analyzed using support vector machines (SVM). METHODS: This retrospective study used data from 207 women with different types and stages of prolapse. Their demographic information, clinical history, and dynamic MRI data were obtained from the database. New MRI measurements were extracted and analyzed based on these reference lines: pubococcygeal line (PCL), mid-pubic line (MPL), true conjugate line (TCL), obstetric conjugate line (OCL), and diagonal conjugate line (DCL). A classification model using SVM was designed to assess the impact of the features (variables) in classifying prolapse into low or high stage. RESULTS: The classification model using SVM can accurately identified anterior prolapse with very high accuracy (>0.90), and apical and posterior prolapse with good accuracy (0.80 - 0.90). Two newly proposed MRI-based features were found to be significant in the identification of anterior and posterior prolapse: the angle between TCL and MPL for anterior prolapse, and the angle between DCL and PCL for posterior prolapse. The overall accuracy of posterior prolapse identification increased from 47% to 80% when the newly proposed MRI-based features were taken into consideration. CONCLUSIONS: The proposed MRI-based measurements are effective in differentiating low and high stages of pelvic organ prolapse, particularly for posterior prolapse.


Assuntos
Imageamento por Ressonância Magnética , Prolapso de Órgão Pélvico/classificação , Prolapso de Órgão Pélvico/diagnóstico , Máquina de Vetores de Suporte , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Modelos Teóricos , Estudos Retrospectivos , Índice de Gravidade de Doença
2.
Nat Genet ; 14(1): 25-32, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8782816

RESUMO

Hereditary multiple exostoses (EXT) is an autosomal dominant condition characterized by short stature and the development of bony protuberances at the ends of all the long bones. Three genetic locl have been identified by genetic linkage analysis at chromosomes 8q24.1, 11p11-13 and 19p. The EXT1 gene on chromosome 8 was recently identified and characterized. Here, we report the isolation and characterization of the EXT2 gene. This gene shows striking sequence similarity to the EXT1 gene, and we have identified a four base deletion segregating with the phenotype. Both EXT1 and EXT2 show significant homology with one additional expressed sequence tag, defining a new multigene family of proteins with potential tumour suppressor activity.


Assuntos
Exostose Múltipla Hereditária/genética , Genes Supressores de Tumor , N-Acetilglucosaminiltransferases , Proteínas/genética , Sequência de Aminoácidos , Sequência de Bases , Mapeamento Cromossômico , Cromossomos Humanos Par 11 , Análise Mutacional de DNA , DNA Complementar , Éxons , Feminino , Humanos , Íntrons , Masculino , Dados de Sequência Molecular , Família Multigênica , Linhagem , Homologia de Sequência de Aminoácidos
3.
Cancer Res ; 59(19): 4890-7, 1999 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-10519401

RESUMO

Mouse transporter protein (MTP), a small, highly conserved mammalian intracellular membrane protein with four putative transmembrane domains, has been implicated in the transport of nucleosides and/or related molecules across intracellular membranes. The production of recombinant MTP in Saccharomyces cerevisiae alters sensitivity of yeast cells to a heterogeneous group of compounds (e.g., antimetabolites, antibiotics, anthracyclines, ionophores, and steroid hormones) by changing the subcellular compartmentalization of these drugs, suggesting that MTP functions similarly in higher organisms. The present study was undertaken to define the intracellular location of MTP in mammalian cells. Native MTP was not detected by indirect immunofluorescence in cell types that expressed MTP mRNA; therefore, a hemagglutinin (HA) epitope-tagged version of MTP was produced in cultured BHK21 cells by transient transfection, and its distribution within cells was determined by confocal microscopy using antibodies directed against the HA epitope and various organellar proteins. Antibodies directed against HA-MTP colocalized with antibodies against late endosomal and lysosomal proteins but not with antibodies against either Golgi or early endosomal proteins. Analysis of subcellular fractions from rat liver by immunoblotting with antibodies directed against MTP demonstrated the presence of a MTP-like protein in Golgi- and lysosome-enriched membranes but not in mitochondria. These results indicate that MTP resides in late endosomes and lysosomes, a finding that is consistent with the proposed role for MTP in the movement of a variety of small molecules across endosomal and lysosomal membranes. MTP shares a number of characteristics with other lysosome-associated proteins. We, therefore, propose that it be redesignated murine lysosome-associated protein transmembrane 4.


Assuntos
Proteínas de Transporte/metabolismo , Resistência a Múltiplos Medicamentos , Lisossomos/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras , Sequência de Aminoácidos , Animais , Proteínas de Transporte/química , Proteínas de Transporte/genética , Fracionamento Celular/métodos , Linhagem Celular , Cricetinae , Endossomos/metabolismo , Técnica Indireta de Fluorescência para Anticorpo , Complexo de Golgi/metabolismo , Humanos , Proteínas de Membrana/química , Proteínas de Membrana/genética , Camundongos , Dados de Sequência Molecular , Nucleosídeos/metabolismo , Ratos , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transfecção
4.
Oncogene ; 8(12): 3369-74, 1993 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8247539

RESUMO

We have used genetic complementation rescue to identify two lethal alleles of D-elg, an ets proto-oncogene related gene of Drosophila. Animals that are hemizygous or trans-heterozygous for the alleles die as pharate adults, demonstrating normal gene function is required to complete Drosophila development. Females trans-heterozygous for the 1(3)902 lethal allele and the previously characterized tne female sterile allele produce embryos with abdominal segmentation defects. This finding implicates a role for the D-elg gene in anterior-posterior patterning. The cloning and sequencing of the lethal alleles identified molecular mutations that may result in ELG protein truncation, altered ELG protein interactions, or defective D-elg mRNA splicing.


Assuntos
Alelos , Drosophila/embriologia , Drosophila/genética , Genes de Insetos/genética , Genes de Insetos/fisiologia , Genes Letais/genética , Genes Letais/fisiologia , Proteínas Proto-Oncogênicas/genética , Fatores de Transcrição , Animais , Desenvolvimento Embrionário e Fetal/fisiologia , Feminino , Heterozigoto , Mutação , Proteínas Proto-Oncogênicas c-ets , Splicing de RNA , RNA Mensageiro/genética
5.
J Mol Biol ; 285(1): 379-89, 1999 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-9878413

RESUMO

Membrane proteins of the ATP-binding cassette (ABC) superfamily are involved in the transport of diverse substrates across organellar and plasma membranes of the mammalian cell. Most human ABC proteins identified to date are associated with genetically linked diseases or clinically relevant phenotypes. We describe a new human half-molecule ABC protein, designated M-ABC1, that contains a predicted single membrane and ATP-binding cassette domain. M-ABC1 is localized to membranes of the mitochondria and its transcript is expressed in all tissues. The N-terminal region of the M-ABC1 protein was shown to function independently as a mitochondrial signal sequence by its ability to target the green fluorescent protein to the mitochondria. The monomeric 60 kDa M-ABC1 protein was chemically crosslinked in vivo into a major protein species of 120-130 kDa, thereby confirming that M-ABC1 exists within a higher ordered ABC protein complex. A dominant negative repression approach using M-ABC1 protein with site-directed mutations in its Walker A motif revealed that the mutant protein was rapidly degraded and indicated that the intact Walker A motif of M-ABC1 was required for its stability. The identification of M-ABC1 extends the known distribution of members of the ABC protein family into the mammalian mitochondrion.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Trifosfato de Adenosina/metabolismo , Cromossomos Humanos Par 7 , Mitocôndrias , Transportador 1 de Cassete de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/biossíntese , Sequência de Aminoácidos , Animais , Sequência de Bases , Células COS , Mapeamento Cromossômico , DNA Complementar , Expressão Gênica , Humanos , Membranas Intracelulares , Dados de Sequência Molecular , Fenótipo , RNA Mensageiro , Células Tumorais Cultivadas
6.
J Bone Miner Res ; 10(2): 325-34, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7754814

RESUMO

Matrix Gla protein (MGP) is, along with osteocalcin, a skeletal member of the family of extracellular mineral-binding Gla proteins. Although the precise function of these proteins remains obscure, circumstantial evidence suggests that they play a role in endochondral ossification. As a first step toward understanding MGP function we have performed a preliminary characterization of its promoter element and studied the developmental pattern of expression of this gene. DNA transfection experiments indicate that the mouse MGP promoter functions better in cells expressing the MGP gene than in cells that do not express the gene. During mouse development, MGP gene expression is detectable as early as day 10.5 of embryonic development (E10.5), before any skeletal structures are identifiable. In situ hybridization analysis shows that MGP mRNA is initially present at the mesenchymal epithelial interphase in lung and limb buds. As development proceeds, MGP gene is predominantly expressed in cells of the chondrocytic lineage in areas that will undergo endochondral ossification as well as in areas that will remain cartilaginous, such as the trachea and bronchi. In growth plate cartilage, MGP mRNA is present in resting, proliferative, and late hypertrophic chondrocytes. Surprisingly, MGP mRNA is absent from the early hypertrophic chondrocytes and from the osteoblasts. Finally, the MGP gene is expressed at a lower level in kidney medulla and uterus smooth muscle but not in brain, spleen, or heart during development. This study demonstrates that during development MGP gene expression occurs early and is predominant at the epithelial mesenchymal interfaces, principally of lung and limb buds, and in cells of the chondrocytic lineage. This finding raises the intriguing possibility that MGP may play distinct roles during embryogenesis and in the adult organism.


Assuntos
Cartilagem/embriologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Osteocalcina/genética , Animais , Sequência de Bases , Biomarcadores Tumorais , Desenvolvimento Ósseo/genética , Desenvolvimento Ósseo/fisiologia , Cartilagem/citologia , Cartilagem/metabolismo , Linhagem Celular , DNA/química , DNA/genética , DNA/metabolismo , Desenvolvimento Embrionário e Fetal/genética , Desenvolvimento Embrionário e Fetal/fisiologia , Lâmina de Crescimento/citologia , Lâmina de Crescimento/embriologia , Lâmina de Crescimento/metabolismo , Membro Posterior/embriologia , Membro Posterior/metabolismo , Hibridização In Situ , Pulmão/embriologia , Pulmão/metabolismo , Camundongos , Dados de Sequência Molecular , Osteoblastos/citologia , Osteoblastos/metabolismo , Regiões Promotoras Genéticas/genética , RNA Mensageiro/metabolismo , TATA Box/genética , Transfecção
7.
J Bone Miner Res ; 15(3): 442-50, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10750558

RESUMO

The EXT genes are a group of putative tumor suppressor genes that previously have been shown to participate in the development of hereditary multiple exostoses (HME), HME-associated and isolated chondrosarcomas. Two HME disease genes, EXT1 and EXT2, have been identified and are expressed ubiquitously. However, the only known effect of mutations in the EXT genes is on chondrocyte function as evidenced by aberrant proliferation of chondrocytes leading to formation of bony, cartilage-capped projections (exostoses). In this study, we have characterized exostosis chondrocytes from three patients with HME (one with EXT1 and two with EXT2 germline mutations) and from one individual with a non-HME, isolated exostosis. At the light microscopic level, exostosis chondrocytes have a stellate appearance with elongated inclusions in the cytoplasm. Confocal and immunofluorescence of in vitro and in vivo chondrocytes showed that these massive accumulations are composed of actin bundled by 1.5-microm repeat cross-bridges of alpha-actinin. Western blot analysis shows that exostosis chondrocytes from two out of three patients aberrantly produce high levels of muscle-specific alpha-actin, whereas beta-actin levels are similar to normal chondrocytes. These findings suggest that mutations in the EXT genes cause abnormal processing of cytoskeleton proteins in chondrocytes.


Assuntos
Actinas/metabolismo , Cartilagem/patologia , Citoesqueleto/patologia , Exostose Múltipla Hereditária/genética , N-Acetilglucosaminiltransferases , Isoformas de Proteínas/metabolismo , Proteínas/genética , Vimentina/metabolismo , Actinina/metabolismo , Western Blotting , Cartilagem/química , Criança , Análise Mutacional de DNA , Exostose/genética , Exostose/patologia , Exostose Múltipla Hereditária/patologia , Humanos , Substâncias Macromoleculares , Microscopia Confocal , Microscopia de Fluorescência , Proteínas/fisiologia
8.
Endocrinology ; 142(1): 165-73, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11145579

RESUMO

Insulin-like growth factor I (IGF-I) is a potent anabolic peptide that mediates most of its pleiotropic effects through association with the IGF type I receptor. Biological availability and plasma half-life of IGF-I are modulated by soluble binding proteins (IGFBPs), which sequester free IGF-I into high affinity complexes. Elevated levels of specific IGFBPs have been observed in several pathological conditions, resulting in inhibition of IGF-I activity. Administration of IGF-I variants that are unable to bind to the up-regulated IGFBP species could potentially counteract this effect. We engineered two IGFBP-selective variants that demonstrated 700- and 80,000-fold apparent reductions in affinity for IGFBP-1 while preserving low nanomolar affinity for IGFBP-3, the major carrier of IGF-I in plasma. Both variants displayed wild-type-like potency in cellular receptor kinase assays, stimulated human cartilage matrix synthesis, and retained their ability to associate with the acid-labile subunit in complex with IGFBP-3. Furthermore, pharmacokinetic parameters and tissue distribution of the IGF-I variants in rats differed from those of wild-type IGF-I as a function of their IGFBP affinities. These IGF-I variants may potentially be useful for treating disease conditions associated with up-regulated IGFBP-1 levels, such as chronic or acute renal and hepatic failure or uncontrolled diabetes. More generally, these results suggest that the complex biology of IGF-I may be clarified through in vivo studies of IGFBP-selective variants.


Assuntos
Cartilagem Articular/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Idoso , Substituição de Aminoácidos , Animais , Neoplasias da Mama , Cartilagem Articular/efeitos dos fármacos , Feminino , Variação Genética , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Fator de Crescimento Insulin-Like I/farmacocinética , Cinética , Taxa de Depuração Metabólica , Mutagênese Sítio-Dirigida , Técnicas de Cultura de Órgãos , Ratos , Ratos Sprague-Dawley , Receptor IGF Tipo 1/metabolismo , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacocinética , Especificidade por Substrato , Sulfatos/metabolismo , Distribuição Tecidual , Células Tumorais Cultivadas
9.
FEBS Lett ; 478(1-2): 89-94, 2000 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-10922475

RESUMO

We have isolated a human cDNA encoding a novel ATP-binding cassette (ABC) protein whose gene was previously localized to chromosome 1q42 [Allikmets et al. (1995) Mamm. Genome 6, 111-117]. The gene transcript is expressed in all human tissues examined, with the highest levels in bone marrow. A non-expressed pseudogene also exists at chromosome 15q13-14. The new protein, which is most similar to the mitochondrial (M)-ABC1 protein, was also localized to mitochondria and therefore designated 'M-ABC2'. The N-terminus of M-ABC2 was shown to contain a mitochondrial-targeting signal sequence.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Mitocôndrias/química , Transportadores de Cassetes de Ligação de ATP/química , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Medula Óssea/metabolismo , Linhagem Celular , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 15/genética , Clonagem Molecular , Perfilação da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Membranas Intracelulares/química , Dados de Sequência Molecular , Filogenia , Mapeamento Físico do Cromossomo , Sinais Direcionadores de Proteínas/genética , Pseudogenes/genética , RNA Mensageiro/análise , RNA Mensageiro/genética , Alinhamento de Sequência , Transfecção
10.
Mol Biochem Parasitol ; 44(2): 195-206, 1991 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2052021

RESUMO

Normal human erythrocytes, preincubated with the oxidizing agent diamide, did not demonstrate any increased permeability, but showed a significant decrease in their ability to transport the nucleoside adenosine. Diamide appeared to have little effect on glucose permeation in uninfected and Plasmodium falciparum infected cells. The inhibition of adenosine transport in human erythrocytes by diamide pretreatment appeared to be unrelated to the inhibition by the established nucleoside transport inhibitor, nitrobenzylthioinosine (NBMPR). An ID50 for diamide of 0.3 mM was determined for 1 microM adenosine transport in human erythrocytes after preincubation for 45 min at 37 degrees C. However, preincubation of diamide (20 mM, 60 min at 37 degrees C) with Babesia bovis-infected bovine erythrocytes resulted in complete inhibition of the capacity of the parasitised cell to transport adenosine and partial inhibition of glucose permeation. By contrast, diamide was shown to have little or no effect on the new or induced nucleoside permeation site in P. falciparum (trophozoite) infected erythrocytes nor on the glucose transporter in these cells. The results further indicate the differences between the normal human erythrocyte nucleoside and glucose transporters and those new or altered transporters in the membrane of P. falciparum or B. bovis-infected red blood cells.


Assuntos
Babesia/metabolismo , Babesiose/metabolismo , Diamida/farmacologia , Eritrócitos/metabolismo , Glucose/metabolismo , Nucleosídeos/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Permeabilidade da Membrana Celular , Eritrócitos/parasitologia , Humanos , Cinética , Malária/metabolismo
11.
Am J Med Genet ; 62(2): 150-9, 1996 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-8882395

RESUMO

Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by the formation of cartilage capped prominences that develop from the epiphyses of the long bones. EXT is heterogeneous with three different locations currently identified on chromosomes 8, 11, and 19. Recently, we identified and studied 12 large multigenerational EXT families. Linkage analyses demonstrates that 6 of these families map to 8q24 and 6 to 11p. None of the families map to the chromosome 19 locus. The results suggest that there are two major loci, on chromosomes 8 and 11, involved in the cause of EXT. The locus on chromosome 19 remains to be confirmed.


Assuntos
Cromossomos Humanos Par 11 , Cromossomos Humanos Par 8 , Exostose Múltipla Hereditária/genética , Exostose Múltipla Hereditária/patologia , Feminino , Ligação Genética , Deformidades Congênitas da Mão/patologia , Humanos , Masculino , Linhagem
12.
J Pharm Sci ; 81(4): 359-61, 1992 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1380076

RESUMO

A rapid and simple high-performance liquid chromatographic (HPLC) method for the analysis of docusate sodium in soft gelatin capsules was developed with progesterone as the internal standard. The method requires a reversed-phase column and a paired-ion technique to separate docusate sodium from other components. A C22 column was used with a mobile phase of acetonitrile:water (70:30) containing 0.005 M tetrabutylammonium phosphate. The flow rate was 1.8 mL/min, and the effluent was monitored at 214 nm. Docusate sodium and progesterone had retention times of 4.5 and 6.8 min, respectively. The proposed HPLC method is linear, accurate, and precise. A mean assay value of 99.6% was obtained by the proposed method when five samples, each containing a composite of 10 capsules, were analyzed. The results obtained by the proposed HPLC, tetra-n-butylammonium iodide titration, and USP XXII HPLC methods are compared.


Assuntos
Cápsulas/química , Química Farmacêutica/métodos , Ácido Dioctil Sulfossuccínico/análise , Gelatina/análise , Calibragem , Cromatografia Líquida de Alta Pressão , Compostos de Amônio Quaternário
13.
Domest Anim Endocrinol ; 8(4): 549-54, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1723938

RESUMO

The objectives of this study were to compare the efficacy of 3-week vs 6-week dietary administration of the beta-adrenergic agonist cimaterol on skeletal muscle growth, and to measure the changes in muscle nucleic acid and protein concentration and content to provide evidence regarding the mechanism(s) by which cimaterol stimulates muscle hypertrophy in growing ruminants. Two groups of 12 Dorset or Dorset-Finn cross ram lambs weighing 36 kg or 33 kg were assigned to treatment intervals of 3 or 6 weeks, respectively. Lambs within each weight group were randomly assigned to receive 0 or 10 ppm cimaterol in a complete mixed diet fed ad libitum. Initial live weights and treatment periods were chosen to achieve similar slaughter weights. Cimaterol increased the mass of three hind leg muscles 30% and 25% on average (both P less than .001) with 3- and 6-week administration, respectively, resulting in identical average muscle weights of treated lambs at both treatment intervals. The mean mass of these 3 muscles, expressed as a percentage of body weight, was increased 18.6% (P less than .001) at both treatment intervals. RNA concentration and content of the semitendinosus muscle were increased 24.8% (P less than .01) and 84.6% (P less than .001), respectively, after 3 weeks of treatment, but neither was significantly different from controls after 6 weeks. DNA concentration in the muscle was reduced 42% (P less than .05) with 3-week cimaterol administration, and was 25% less than controls (P greater than .05) in lambs fed cimaterol for 6 weeks. Total DNA content of the semitendinosus was unchanged at either treatment interval.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Agonistas Adrenérgicos beta/farmacologia , Etanolaminas/farmacologia , Músculos/efeitos dos fármacos , Ovinos/crescimento & desenvolvimento , Animais , DNA/análise , Masculino , Desenvolvimento Muscular , Músculos/química , RNA/análise , Distribuição Aleatória
14.
Domest Anim Endocrinol ; 8(4): 537-48, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1686222

RESUMO

The objective of this study was to determine if acute and chronic changes in circulating metabolic hormone and metabolite concentrations are associated with beta-agonist-induced nutrient repartitioning in young growing lambs. Two groups of 12 Dorset and Dorset-Finn cross ram lambs weighing 36 or 33 kg live weight were assigned to 3- or 6-week treatment intervals, respectively, to achieve similar slaughter weights. Six lambs within each treatment interval were fed ad libitum a complete mixed high-concentrate diet containing either 0 or 10 ppm cimaterol. During the first 12 hr of cimaterol administration plasma somatotropin (ST), thyroxine (T4), and triiodothyronine (T3) concentrations were not altered by treatment, but plasma insulin, glucose, non-esterified fatty acids (NEFA) and glycerol concentrations were elevated 2 hr after ingestion. These acute responses suggest direct stimulation of glycogenolysis and lipolysis by cimaterol, which is characteristic of beta-adrenergic alteration of carbohydrate and lipid metabolism. Chronic administration of cimaterol significantly decreased insulin concentrations by 36% and 52% at 3 and 6 weeks, respectively, while glucose concentrations remained unchanged. Serum IGF-I concentrations were not significantly altered by cimaterol. T4 levels were reduced 22.1% after 3 weeks of cimaterol treatment. Although plasma NEFA concentrations were chronically elevated 56% to 65% in lambs fed cimaterol, plasma glycerol concentrations remained at baseline levels. The relative changes in plasma NEFA and glycerol concentrations are consistent with a decreased rate of lipogenesis, rather than an increase in lipolysis.


Assuntos
Agonistas Adrenérgicos beta/farmacologia , Etanolaminas/farmacologia , Hormônios/sangue , Ovinos/metabolismo , Ração Animal , Animais , Glicemia/análise , Metabolismo dos Carboidratos , Ácidos Graxos não Esterificados/sangue , Glicerol/sangue , Hormônio do Crescimento/sangue , Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Modelos Lineares , Metabolismo dos Lipídeos , Masculino , Hormônios Tireóideos/sangue
15.
Domest Anim Endocrinol ; 12(2): 143-56, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7600765

RESUMO

The purpose of this study was to determine the effects of exogenous recombinant bovine somatotropin (bST) treatment on whole-body glycemic responsiveness and sensitivity to exogenous insulin in preruminant and ruminant lambs. Twelve milk-fed (MF) and 12 ruminating (RUM) wether lambs weighing 20 +/- 0.6 kg were assigned to one of four treatment groups: MF control, MF plus bST, RUM control, and RUM plus bST. Lambs received a daily subcutaneous injection of 160 micrograms of sometribove (recombinant methionyl bST) bST/kg live weight or the equivalent volume of sterile water (control) for 10 d. The MF lambs had higher plasma insulin and nonessential fatty acids and lower acetate concentrations than RUM lambs (all P < 0.05). Plasma insulin-like growth factor concentrations were similar in both. The administration of bST raised plasma insulin-like growth factor-1 (P < 0.001) and insulin (P < 0.05) in MF and RUM lambs, but with greater effect in MF lambs (P < 0.01 and P < 0.1, respectively). Six successive dose-incremented insulin challenges (50, 100, 200, 300, 500, and 700 mU/kg body weight) were performed two per day on Days 8, 9, and 10 of treatment. Dose-response curves for absolute decline in glucose concentration from preinjection baseline to nadir were used to characterize whole-body responsiveness and sensitivity (ED50) to insulin. Somatotropin treatment increased insulin ED50 values 64 and 70% (P < 0.07) in RUM and MF lambs, respectively, suggesting that sensitivity to insulin was reduced. Insulin ED50 values were 40% higher in MF than in RUM lambs (P < 0.05). Insulin clearance rates increased with each dose increment to 300 mU/kg body weight (P = 0.001) and were 50% lower in bST-treated MF lambs than in all other treatment groups (P < 0.05). Results suggest that somatotropin modulates the insulin control of glucose homeostasis similarly in preruminant and ruminant lambs by decreasing sensitivity but not maximum responsiveness.


Assuntos
Glicemia/análise , Hormônio do Crescimento/farmacologia , Insulina/farmacologia , Rúmen/fisiologia , Ovinos/metabolismo , Envelhecimento/sangue , Envelhecimento/metabolismo , Animais , Nitrogênio da Ureia Sanguínea , Relação Dose-Resposta a Droga , Ácidos Graxos não Esterificados/sangue , Glucose/metabolismo , Homeostase/fisiologia , Insulina/sangue , Insulina/farmacocinética , Masculino , Rúmen/efeitos dos fármacos , Ovinos/crescimento & desenvolvimento
16.
J Anim Sci ; 53(6): 1473-81, 1981 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7341614

RESUMO

To test whether lipogenesis is limited by lack of glucose precursors, 45 lambs (30 kg) were randomly grouped by sex and initial weight and fed ad libitum in pens of three in a growth and slaughter experiment. The diets consisted of a basal mixed chopped hay (C), hay + 4% butylene glycol (BD) and hay + 4% propylene glycol (PG). On a dry matter basis, the crude protein content and in vitro true digestibility of the hay were 9.6 and 64%, respectively. Growth and feed intake were recorded. After 13 weeks, the lambs were killed. Blood glucose concentrations, feed intake and weight gains did not differ between diets, but intake and weight gains were minimal. BD increased (P greater than .01) blood ketones. Perirenal adipose tissue fatty acid synthetase (FAS) activity averaged 2.6, 2.4 and 1.2 nmole NADPH oxidized/mg cytosol protein/min for the BD, PG and C lambs, respectively. Values for both glycol-fed groups were higher (P greater than .01) than the control value. Carcass chemical composition followed a similar pattern, with BD, PG and C carcasses containing 38.1, 39.2 and 35.8% dry matter, respectively, and the dry matter containing 36.6, 39.4 and 30.0% fat, respectively. Carcasses of the BD and PG lambs did not differ significantly from each other, but both groups had more (P greater than .05) fat and less (P greater than .05) protein and ash than did the C carcasses, suggesting that the chemical composition of lamb carcasses may be nutritionally manipulated. The essentially equal response of adipose FAS activity and carcass fat in lambs fed PG and lambs fed BD indicates that the inclusion of glucogenic substances did not promote lipogenesis in these lambs fed at or slightly above maintenance.


Assuntos
Composição Corporal/efeitos dos fármacos , Butileno Glicóis/farmacologia , Ácido Graxo Sintases/metabolismo , Lipídeos/biossíntese , Propilenoglicóis/farmacologia , Ovinos/metabolismo , Tecido Adiposo/metabolismo , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Dieta , Feminino , Cetonas/sangue , Masculino
17.
J Anim Sci ; 63(6): 2018-27, 1986 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-3818475

RESUMO

In two experiments, a total of 46 Finn Cross and Dorset lambs were artificially group-reared. Thirty eight were weaned abruptly at 14 d of age from a commercial milk replacer (MR) to a dry starter diet (SD). Lambs were self-fed cool (10 to 15 C) MR reconstituted to 25% dry matter (DM). The ground (2-mm screen) SD averaged 26.2% crude protein and 7.4% fat (DM basis). For both experiments, birth and weaning weights averaged 3.8 and 8.0 kg, respectively. Experiment 1 tested a strategy for encouraging postweaning DM intake. Fifteen lambs received MR reconstituted to 33% DM from d 11 to 14, and 15 lambs received standard 25% DM MR. Between d 14 and 15, intakes of DM, gross energy, crude protein and water dropped 86, 89, 85 and 64%, respectively. Lambs doubled their birth weights during the milk-feeding period and consumed 1.41 kg SD between d 14 and 25. The MR reconstitution rate did not affect weaning weight, postweaning SD or water intake, or growth check (GC, P greater than .10). Postweaning GC averaged 12.2 d and was not influenced (P greater than .10) by birth weight, sex or weaning weight. Mortality and disease rates under these conditions were negligible. Experiment 2 was designed to differentiate between the dual effects at weaning of altering the type of diet and of reducing the level of nutrient intake. Eight lambs were weaned to SD at 14 d, and eight lambs were bottle-fed isocaloric levels of MR from d 12 to 30. At weaning, plasma glucose concentration declined 1.4 mM from 6.7 mM due to fasting and an additional 1.0 mM due to the change of the type of diet (P less than .01). Plasma acetate and urea N concentrations rose steadily after d 16 in the SD-weaned lambs, but not in the MR-fed lambs (P less than .01), suggesting that the SD-weaned lambs absorbed ruminal fermentation products. These results indicate that artificially reared lambs may be routinely weaned to a dry diet at 14 d of age. The major alterations in plasma metabolites that occur within 6 to 8 d after abrupt weaning may define the period when these lambs become functional ruminants.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Peso Corporal , Ovinos/metabolismo , Desmame , Animais , Ovinos/crescimento & desenvolvimento
18.
J Anim Sci ; 73(8): 2493-502, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8567487

RESUMO

At present less than 30% of the market lambs slaughtered in the United States meet the requirements for leanness and muscling as specified in the "Certified Fresh American Lamb" program established in 1990 by the American Sheep Industry Association (ASI). Carcass composition of slaughter lambs is determined by stage of growth relative to mature size, genotype, sex, and matching dietary nutriment to nutrient requirements for lean tissue growth. On the average, current production strategies produce carcasses that contain excessive amounts of fat, impeding optimized efficiency at all levels of production. Use of large-mature-size terminal sires, feeding rumen-escape dietary protein, feeding intact males, and slaughtering at appropriate weights all improve composition of gain. Improvements of 10 to 20% in rates of gain and efficiency of nutrient use and similar reductions in feed cost can be achieved with each of these management strategies. Results from several experiments demonstrate that these effects are additive and provide a measure of the true genetic capacity for protein accretion rate in growing lambs. Adoption of these management strategies will allow lambs to be slaughtered at a younger age, which may improve meat quality and concurrently reduce the amount of nitrogen waste returned to the environment. Potential for further manipulation of composition exists through more accurately defining nutrient requirements of growing lambs and through use of metabolism modifiers. Maintaining a competitive, profitable, and sustainable sheep industry depends on continued improvement of production efficiency, preferably in systems with high reproductive rates.


Assuntos
Composição Corporal/fisiologia , Carne/normas , Ovinos/crescimento & desenvolvimento , Ração Animal/normas , Animais , Composição Corporal/efeitos dos fármacos , Feminino , Genótipo , Hormônio do Crescimento/farmacologia , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Masculino , Nitrogênio/metabolismo , Caracteres Sexuais , Ovinos/metabolismo , Ovinos/fisiologia , Estados Unidos , United States Department of Agriculture , Aumento de Peso/efeitos dos fármacos , Aumento de Peso/fisiologia
19.
J Anim Sci ; 75(9): 2328-34, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9303449

RESUMO

The objective of this experiment was to compare vaccination schedules for ewes and their lambs to raise antibody concentrations to epsilon-toxin of Clostridium perfringens, the causative agent of enterotoxemia. Half of 200 Finnsheep x Dorset ewes were vaccinated with C. perfringens type D toxoid vaccine 3 wk before lambing. Serum samples were obtained from 20 ewes that were to be vaccinated and 20 ewes that would remain unvaccinated before treatment and at wk 2, 1, and 0 before the start of lambing. Antibody concentrations in sera of unvaccinated ewes remained at 2 IU/mL, but they peaked in vaccinated ewes at 15 IU/mL by wk 1 before lambing. Lambs from each of the first 13 and the first 14 sets of triplets from vaccinated and unvaccinated ewes, respectively, received one of three vaccination treatments: no vaccine (control), vaccination on d 1 and 21 of age, or vaccination on d 21 and 42 of age. Antibody concentrations declined in sera of vaccinated ewes from 8.5 IU/mL immediately after lambing to 3 IU/mL 12 wk later. Vaccination of lambs did not increase sera antibody concentration. However, prepartum vaccination of ewes significantly increased lamb antibody concentrations (19 IU/mL) compared with lambs reared by unvaccinated ewes (2 IU/mL). Vaccination of ewes resulted in lambs with higher antibody concentrations until wk 10 postpartum. Concentrations declined to .6 IU/mL in all lambs at 12 wk. Because concentrations of .2 IU/mL may be protective, these results indicate that vaccination of ewes before lambing imparts passive protection in lambs to 12 wk of age, whereas vaccination of young lambs provides no added protection.


Assuntos
Anticorpos Antibacterianos/sangue , Toxinas Bacterianas/imunologia , Vacinas Bacterianas/administração & dosagem , Clostridium perfringens/imunologia , Enterotoxemia/prevenção & controle , Doenças dos Ovinos/prevenção & controle , Vacinação/veterinária , Animais , Animais Recém-Nascidos , Anticorpos Antibacterianos/imunologia , Toxinas Bacterianas/sangue , Vacinas Bacterianas/imunologia , Clostridium perfringens/metabolismo , Enterotoxemia/sangue , Enterotoxemia/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Esquemas de Imunização , Tamanho da Ninhada de Vivíparos , Gravidez , Ovinos , Doenças dos Ovinos/sangue , Doenças dos Ovinos/imunologia , Fatores de Tempo , Vacinação/métodos
20.
J Anim Sci ; 67(5): 1167-74, 1989 May.
Artigo em Inglês | MEDLINE | ID: mdl-2737977

RESUMO

The objective of this study was to compare rebreeding activities of spring- vs fall-lambing Polypay, Dorset, St. Croix and Targhee ewes that either suckled their lambs for 40 d or had lambs weaned at birth. Seasonal effects of male fertility were reduced by utilizing an excess number of fertile rams in the spring. Plasma concentrations of progesterone were monitored to assess days to the first normal ovulation, days to conception and estrous vs anestrous activity. Breed, season and lactation affected the rebreeding performance. Dorset ewes had similar conception rates between spring and fall but a shorter interval from lambing to first ovulation in the fall. Polypay and Targhee ewes were the opposite; they had higher conception rates in fall than in spring matings with no seasonal influence on postpartum interval. Postpartum ewes in the fall had higher conception rates, and fewer of these ewes became anestrous or had estrous cycles of abnormal duration than of those ewes lambing in the spring. Ewes that suckled for 40 d in the spring had delayed estrous activity, but when these ewes became estrual they had higher conception rates than ewes whose lambs were weaned at birth. Lactation had no inhibitory affect on the postpartum interval of fall lambing ewes. These data suggest that the response of different breeds to various components of postpartum fertility varies with season and management of the flock.


Assuntos
Fertilidade , Lactação/fisiologia , Período Pós-Parto/fisiologia , Ovinos/fisiologia , Animais , Cruzamento , Estro/fisiologia , Feminino , Masculino , Gravidez , Distribuição Aleatória , Estações do Ano , Ovinos/genética
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