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1.
J Occup Rehabil ; 33(1): 179-188, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-35927599

RESUMEN

PURPOSE: Early intervention vocational rehabilitation (EIVR) can improve return to work (RTW) outcomes for people with spinal cord injury (SCI). However, mechanisms explaining how and why EIVR works are not well understood. This study aims to develop a conceptual framework describing key mechanisms of EIVR intervention effect following SCI. METHODS: We synthesised data from a realist literature review with data from interviews of people with SCI (n = 30), a survey of people with SCI who had received EIVR (n = 37), a focus group of EIVR providers and a focus group of community vocational providers. We first synthesised the literature review and interviews to develop an initial programme theory describing the contexts in which mechanisms are activated to produce EIVR outcomes. Then we used data from the survey and focus groups to further refine the EIVR programme theory. Finally, a conceptual framework was developed to support knowledge dissemination. RESULTS: By ensuring consistent messaging across the multi-disciplinary team, EIVR programmes establish and maintain hope that work is possible following injury. Conversations about work allow individuals to determine the priority of work following injury. These conversations can also improve self-efficacy by providing individualized support to envisage pathways toward RTW goals and maintain worker identity. The synthesised study findings highlight the contexts and resources required to trigger activation of these mechanisms. CONCLUSIONS: EIVR key mechanisms of effect are not specific to SCI as a health condition, therefore enabling this framework to be applied to other populations who face similar impairments and return to work barriers.


Asunto(s)
Rehabilitación Vocacional , Traumatismos de la Médula Espinal , Humanos , Reinserción al Trabajo , Ocupaciones , Grupos Focales , Traumatismos de la Médula Espinal/rehabilitación
2.
Phys Occup Ther Pediatr ; 38(5): 510-526, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29236556

RESUMEN

AIM: To develop a model for understanding mechanisms of change in health outcomes for riders with disabilities participating in therapeutic horse riding (THR). METHODS: Using grounded theory methods we collected and analyzed data from interviews with 16 child riders and 18 caregivers, teachers and primary therapists, and from participant-observation during THR sessions. RESULTS: The central concept underpinning the model illustrating mechanisms of change was "gaining the tools to go on." Riders' experiences suggested the THR landscape (i.e., "where the tools are gathered") allowed for an expanded range of experiences in which riders could participate. Riders experienced an expansion of self-concept by learning to move, succeed, connect, and adapt (i.e., "the tools gathered") within the THR landscape. Riders then iteratively translated an expanded view of self into other environments, reflecting "how and where the tools are used." CONCLUSION: Findings suggest that positive changes in health arise from riders' experiences of learning and agency within the THR therapeutic landscape, and from the influence of these experiences on a child's developing self-concept. This article considers the wider impact of THR on children's health, beyond a focus on changes in physical outcomes.


Asunto(s)
Personas con Discapacidad/rehabilitación , Terapía Asistida por Caballos/métodos , Adolescente , Niño , Femenino , Teoría Fundamentada , Humanos , Masculino , Nueva Zelanda , Autoimagen
3.
J Evol Biol ; 29(11): 2256-2265, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27467980

RESUMEN

Sexual signalling is predicted to shape the evolution of sex-specific ornamentation, and establishing the costs and benefits of ornamentation and the information that ornamentation provides to receivers is necessary to evaluating this adaptive function. Here, we assessed the adaptive function of a common colour ornament in insects, melanin wing ornamentation, using the dragonfly Pachydiplax longipennis. We hypothesized that greater ornamentation would improve territory-holding success by decreasing aggression that males receive from territorial rivals, but that more ornamented males may have shorter lifespans. Using mark-recapture field observations, we found that more ornamented males had greater territory-holding success and that viability selection did not act on wing melanization. We then compared the aggression of territorial rivals to decoy males before and after experimentally augmenting wing melanization, finding that males significantly reduced aggression following the manipulation. We next hypothesized that wing melanization would signal fighting ability to territorial rivals by reflecting condition via investment in the costly melanin synthesis pathway. We observed a positive relationship between ornamentation and the likelihood of winning territorial disputes, suggesting that wing melanization provides information about fighting ability to rivals. We also found a positive relationship between melanin-based immune defence and ornamentation, supporting a link between the signal and condition. We conclude that wing melanization is a condition-related signal of fighting ability and suggest that this may be a common mechanism promoting the evolution of melanin ornamentation.


Asunto(s)
Color , Melaninas , Odonata , Territorialidad , Animales , Evolución Biológica , Femenino , Masculino , Alas de Animales
4.
J Evol Biol ; 29(10): 1977-1985, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27316646

RESUMEN

Offspring quantity and quality are components of parental fitness that cannot be maximized simultaneously. When the benefits of investing in offspring quality decline, parents are expected to shift investment towards offspring quantity (other reproductive opportunities). Even when mothers retain complete control of resource allocation, offspring control whether to allocate investment to growth or development towards independence, and this shared control may generate parent-offspring conflict over the duration of care. We examined these predictions by, in a captive colony, experimentally removing tadpoles of the strawberry poison frog (Oophaga pumilio) from the mothers that provision them with trophic eggs throughout development. Tadpoles removed from their mothers were no less likely to survive to nutritional independence (i.e. through metamorphosis) than were those that remained with their mothers, but these offspring were smaller at metamorphosis and were less likely to survive to reach adult size, even though they were fed ad libitum. Tadpoles that remained with their mothers developed more slowly than those not receiving care, a pattern that might suggest that offspring extracted more care than was in mothers' best interests. However, the fitness returns of providing care increased with offspring development, suggesting that mothers would be best off continuing care until tadpoles initiated metamorphosis. Although the benefits of parental investment in offspring quality are often thought to asymptote at high levels, driving parent-offspring conflict over weaning, this assumption may not hold over natural ranges of investment, with selection on both parents and offspring favouring extended durations of parental care.


Asunto(s)
Conducta Materna , Ranidae , Reproducción , Animales , Anuros , Huevos , Larva , Metamorfosis Biológica
6.
Nat Genet ; 11(4): 459-61, 1995 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-7493033

RESUMEN

Opitz syndrome (OS, McKusick 145410) is a well described genetic syndrome affecting multiple organ systems whose cardinal manifestations include widely spaced eyes and hypospadias (Fig. 1). It was first reported as two separate entities, BBB syndrome, and G syndrome. However, subsequent reports of families in which the BBB and G syndrome segregated within a single kindred suggested that they were a single clinical entity. Although the original pedigrees were consistent with X-linked and autosomal dominant inheritance, male-to-male transmission in subsequent reports suggested that OS was inherited as an autosomal dominant trait. Here we report that OS is a heterogeneous disorder, with an X-linked and an autosomal locus. Three families were linked to DXS987 in Xp22, with a lod score of 3.53 at zero recombination. Five families were linked to D22S345 from chromosome 22q11.2, with a lod score of 3.53 at zero recombination. This represents the first classic multiple congenital anomaly syndrome with an X-linked and an autosomal form.


Asunto(s)
Anomalías Múltiples/genética , Cromosomas Humanos Par 22 , Heterogeneidad Genética , Hipertelorismo/genética , Cromosoma X , Preescolar , Femenino , Ligamiento Genético , Humanos , Hipospadias/genética , Escala de Lod , Masculino , Linaje , Síndrome
7.
Science ; 167(3924): 1504-6, 1970 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-17750348

RESUMEN

Remains of Sigmodon minor and Sigmodon medius, extinct cotton rats comprising the medius species group, have been recovered from both Kansas and Arizona. Sigmodon minor evolved from Sigmodon medius, and the available evidence suggests that Kansas populations of Sigmodon minor were derived from Kansas populations of Sigmodon medius, while Arizona populations of Sigmodon minor were derived from Arizona populations of Sigmodon medius. This multiple origin of a single mammalian species is similar to the origin proposed by Carleton Coon for the races (subspecies) of Homo sapiens.

8.
Orthod Craniofac Res ; 12(4): 271-81, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19840279

RESUMEN

OBJECTIVE: Various lines of evidence suggest that face shape may be a predisposing factor for non-syndromic cleft lip with or without cleft palate (CL/P). In the present study, 3D surface imaging and statistical shape analysis were used to evaluate face shape differences between the unaffected (non-cleft) parents of individuals with CL / P and unrelated controls. METHODS: Sixteen facial landmarks were collected from 3D captures of 80 unaffected parents and 80 matched controls. Prior to analysis, each unaffected parent was assigned to a subgroup on the basis of prior family history (positive or negative). A geometric morphometric approach was utilized to scale and superimpose the landmark coordinate data (Procrustes analysis), test for omnibus group differences in face shape, and uncover specific modes of shape variation capable of discriminating unaffected parents from controls. RESULTS: Significant disparity in face shape was observed between unaffected parents and controls (p < 0.01). Notably, these changes were specific to parents with a positive family history of CL/P. Shape changes associated with CL/P predisposition included marked flattening of the facial profile (midface retrusion), reduced upper facial height, increased lower facial height, and excess interorbital width. Additionally, a sex-specific pattern of parent-control difference was evident in the transverse dimensions of the nasolabial complex. CONCLUSIONS: The faces of unaffected parents from multiplex cleft families displayed meaningful shape differences compared with the general population. Quantitative assessment of the facial phenotype in cleft families may enhance efforts to discover the root causes of CL/P.


Asunto(s)
Labio Leporino/genética , Fisura del Paladar/genética , Cara/anatomía & histología , Predisposición Genética a la Enfermedad , Padres , Estudios de Casos y Controles , Cefalometría , Salud de la Familia , Femenino , Humanos , Imagenología Tridimensional , Labio/anatomía & histología , Masculino , Desarrollo Maxilofacial/genética , Nariz/anatomía & histología , Órbita/anatomía & histología , Fotogrametría , Análisis de Componente Principal , Factores Sexuales , Dimensión Vertical , Cigoma/anatomía & histología
9.
J Mater Sci Mater Med ; 20(4): 883-8, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19083082

RESUMEN

Melt quenched silicate glasses containing calcium, phosphorous and alkali metals have the ability to promote bone regeneration and to fuse to living bone. These glasses, including 45S5 Bioglass((R)) [(CaO)(26.9)(Na(2)O)(24.4)(SiO(2))(46.1)(P(2)O(5))(2.6)], are routinely used as clinical implants. Consequently there have been numerous studies on the structure of these glasses using conventional diffraction techniques. These studies have provided important information on the atomic structure of Bioglass((R)) but are of course intrinsically limited in the sense that they probe the bulk material and cannot be as sensitive to thin layers of near-surface dissolution/growth. The present study therefore uses surface sensitive shallow angle X-ray diffraction to study the formation of amorphous calcium phosphate and hydroxyapatite on Bioglass((R)) samples, pre-reacted in simulated body fluid (SBF). Unreacted Bioglass((R)) is dominated by a broad amorphous feature around 2.2 A(-1) which is characteristic of sodium calcium silicate glass. After reacting Bioglass((R)) in SBF a second broad amorphous feature evolves ~1.6 A(-1) which is attributed to amorphous calcium phosphate. This feature is evident for samples after only 4 h reacting in SBF and by 8 h the amorphous feature becomes comparable in magnitude to the background signal of the bulk Bioglass((R)). Bragg peaks characteristic of hydroxyapatite form after 1-3 days of reacting in SBF.


Asunto(s)
Fosfatos de Calcio/química , Cerámica , Durapatita/química , Difracción de Rayos X/métodos , Propiedades de Superficie
10.
J Econ Entomol ; 100(2): 283-90, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17461048

RESUMEN

Green lacewings are widely used biological control agents for various insect pests. To meet the needs of growers, green lacewings are being mass-reared commercially around the world. A common salt shaker has been used regularly to distribute eggs into Verticel lacewing larval rearing units. This technique is time consuming and inefficient because the number of eggs distributed in each cell is inconsistent. The multiple orifice distribution (MOD) system described here greatly improved egg distribution efficiency by increasing the percentage of Verticel cells containing the desired one to four eggs per cell (i.e., 40.8 and 52.1% by using salt shaker method versus 61.9% by using the MOD system). This mechanical system significantly reduced the labor and time involved in the process and would cost under $3500. In addition, this new system could be modified for distribution of other insect eggs.


Asunto(s)
Entomología/métodos , Insectos/crecimiento & desarrollo , Animales , Entomología/economía , Entomología/instrumentación , Insectos/fisiología , Larva/crecimiento & desarrollo , Larva/fisiología , Control Biológico de Vectores/economía
11.
Vet Comp Orthop Traumatol ; 19(4): 219-27, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17143394

RESUMEN

The tibial tuberosity advancement (TTA) procedure was developed to treat dogs with cranial cruciate ligament deficient stifles. A retrospective, descriptive study was performed on 57 dogs that underwent unilateral or bilateral TTA. Medical records were reviewed and pre-, postoperative and follow-up radiographs were evaluated for patellar ligament-tibial plateau angle (alpha), distance of the tibial tuberosity advancement and progression of degenerative joint disease. A questionnaire was sent to all owners to obtain their assessment of the procedural outcome. Sixty-five stifles in 57 dogs received a TTA. Mean age was 5.2 +/- 2.5 years while mean weight was 39.7 +/- 11.9 kg. Eighteen breeds were represented with Labrador retrievers and mixed breeds predominating. The mean duration of lameness prior to surgery was 6.2 +/- 6.7 months, with a median lameness score of 3/4. Fifty-nine percent of cases encountered complications, the majority of which were minor. Major post-operative complications were uncommon but consisted of implant failure, tibial crest displacement and medial meniscal tears. The mean radiographic preoperative angle alpha was 100 degrees, while the postoperative was 95.5 degrees. Mean osteoarthrosis scores were significantly different between preoperative and follow-up radiographs with 67% of cases showing radiographic progression. Seventy percent of owners responded to the survey with overall outcome considered good to excellent in 90%. Activity level was improved in 90% of responses. TTA subjectively appears to be a useful alternative in the management of cranial cruciate ligament disease. Few severe complications were encountered. Good clinical outcome and owner satisfaction was reported with the procedure in this set of cases.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Ligamento Cruzado Anterior/cirugía , Perros/lesiones , Inestabilidad de la Articulación/veterinaria , Meniscos Tibiales/cirugía , Rodilla de Cuadrúpedos/lesiones , Rodilla de Cuadrúpedos/cirugía , Animales , Ligamento Cruzado Anterior/diagnóstico por imagen , Perros/cirugía , Femenino , Puntaje de Gravedad del Traumatismo , Inestabilidad de la Articulación/diagnóstico por imagen , Inestabilidad de la Articulación/epidemiología , Inestabilidad de la Articulación/cirugía , Cojera Animal , Masculino , Maryland/epidemiología , Linaje , Complicaciones Posoperatorias/veterinaria , Radiografía , Rango del Movimiento Articular , Estudios Retrospectivos , Rodilla de Cuadrúpedos/diagnóstico por imagen , Encuestas y Cuestionarios , Virginia/epidemiología
12.
Biochim Biophys Acta ; 1164(3): 252-60, 1993 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-8102071

RESUMEN

The literature reported DPP-IV substrate specificity includes oligopeptides with a penultimate Pro, Hyp or Ala residue. Bovine GRF is a substrate for DPP-IV and is rapidly degraded by the enzyme via removal of its N-terminal Tyr-Ala. Incubation of selected GRF analogs from the [X2,Ala15,Leu27]bGRF(1-29)NH2 series with a porcine-kidney-derived DPP-IV in PBS (pH 7.4) resulted in cleavage at the X2-Asp3 bond. The extent of enzymatic hydrolysis varied with X2 as reflected in the following relative cleavage rates: Ala2 (100%), Ser2 (4%), Thr2 (2.5%), Val2 (0.53%), Ile2 (0%). These cleavages were sequestered when similar experiments were performed in the presence of the DPP-IV-specific inhibitor N-epsilon-(p-NO2-benzyloxycarbonyl)-Lys-Pro-OH. A side reaction, buffer-induced deamidation of Asn8, contributed less than 5% of the total substrate degradation. Although our finding qualitatively extends the DPP-IV substrate specificity to also include N-terminal X-Ser, X-Thr and X-Val sequences, quantitatively, relatively fast cleavages of the GRFs with Ala2 make the latter preferred substrates for DPP-IV. The data presented here indicates that the observed GRF(3-29) fragment formation upon incubation of Ser2- and Thr2-substituted bGRF analogs in bovine plasma could have been DPP-IV-related.


Asunto(s)
Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/metabolismo , Hormona Liberadora de Hormona del Crecimiento/metabolismo , Riñón/enzimología , Serina , Treonina , Valina , Animales , Tampones (Química) , Bovinos , Dipeptidil Peptidasa 4 , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/antagonistas & inhibidores , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/química , Hormona Liberadora de Hormona del Crecimiento/análogos & derivados , Semivida , Especificidad por Sustrato , Porcinos
13.
J Nematol ; 37(4): 473-6, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19262893

RESUMEN

Grain yields of spring wheat (Triticum aestivum L. cvs. AC Barrie, AC Walton, AC Wilmot, Belvedere, Glenlea) in field plots over a 3-year period were increased (P < 0.001) by an average of 0.56 (25.1%) and 1.17 (52.5%) tonnes/ha in comparison to untreated check plots when aldicarb at 2.24 kg or fosthiazate at 13.5 a.i./ha, respectively, were broadcast and incorporated into the soil to suppress nematodes. The planned F test using orthogonal coefficients indicated that the mean response of grain yields to nematicide treatments of AC Barrie and Glenlea, which are grown primarily in the prairie provinces of Canada, was greater (48.5%) than the mean response of Belvedere, AC Walton, and AC Wilmot (33.7%), which are more common in the Maritime region of Canada (P < 0.001). Root lesion nematodes (primarily Pratylenchus penetrans) in wheat roots and in root zone soil at harvest were reduced by the nematicide applications (P < 0.001). Bacterial-feeding nematodes (primarily Diplogaster lheritieri (Maupas)) in root zone soil were also suppressed by fosthiazate (P < 0.01) but not by aldicarb. These data indicate that root lesion nematodes cause substantial yield losses in spring wheat in the Maritime region of Canada.

14.
Am J Psychiatry ; 155(2): 220-5, 1998 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9464201

RESUMEN

OBJECTIVE: The authors investigated the theoretical and clinical role of depression among cocaine abusers in treatment. METHOD: Eighty-nine cocaine-abusing patients underwent 2 weeks of substance abuse treatment. Posttreatment major depressive disorder, depressive symptoms before and after substance abuse treatment, and alcohol diagnoses were assessed and their relation to pretreatment substance use, cravings in high-risk situations, and 3-month follow-up status was examined. RESULTS: High rates of major depressive disorder were found but were unrelated to pretreatment substance use. The decrease in depressive symptoms during treatment was independent of major depressive disorder or alcohol diagnoses and predicted treatment attrition. Higher levels of depressive symptoms during treatment were associated with greater urge to use cocaine, alcohol, and other drugs in high-risk situations. Concurrent major depressive disorder and depressive symptoms did not predict cocaine use at follow-up. However, patients who had an alcohol relapse episode experienced more depressive symptoms during treatment than did those who abstained. CONCLUSIONS: The results highlight the relationship of depression to alcohol use among cocaine abusers and suggest a need for further studies of the association between depression and substance use disorders.


Asunto(s)
Alcoholismo/epidemiología , Trastornos Relacionados con Cocaína/terapia , Trastorno Depresivo/epidemiología , Adolescente , Adulto , Alcoholismo/diagnóstico , Análisis de Varianza , Trastornos Relacionados con Cocaína/epidemiología , Depresión/diagnóstico , Depresión/epidemiología , Trastorno Depresivo/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Recurrencia , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Centros de Tratamiento de Abuso de Sustancias , Resultado del Tratamiento
15.
Neurology ; 41(10): 1675-6, 1991 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-1922817

RESUMEN

A young man with headache was unable to sneeze despite a strong sensory urge to do so. Magnetic resonance imaging revealed a cystic neoplasm in the medulla oblongata that presumably interrupted the efferent arc of the sneezing reflex.


Asunto(s)
Astrocitoma/fisiopatología , Neoplasias Encefálicas/fisiopatología , Bulbo Raquídeo/fisiopatología , Estornudo , Adulto , Astrocitoma/complicaciones , Neoplasias Encefálicas/complicaciones , Humanos , Masculino
16.
Neurology ; 29(5): 662-9, 1979 May.
Artículo en Inglés | MEDLINE | ID: mdl-571564

RESUMEN

Two patients had bilateral facial myokymia in association with polyradiculoneuropathy. Characteristic electromyographic findings allow polyradiculoneuropathy to be differentiated from other causes of facial movements, and support the possibility that extraaxial facial nerve involvement is another cause of facial myokymia.


Asunto(s)
Músculos Faciales/fisiopatología , Parálisis Facial/fisiopatología , Polirradiculoneuropatía/fisiopatología , Adulto , Nervio Facial/fisiopatología , Femenino , Humanos , Persona de Mediana Edad , Conducción Nerviosa , Parestesia/fisiopatología , Nervio Peroneo/fisiopatología , Nervio Tibial/fisiopatología , Nervio Cubital/fisiopatología
17.
Psychol Bull ; 127(4): 504-19, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11439709

RESUMEN

All published research examining effects of humor and laughter on physical health is reviewed. Potential causal mechanisms and methodological issues are discussed. Laboratory experiments have shown some effects of exposure to comedy on several components of immunity, although the findings are inconsistent and most of the studies have methodological problems. There is also some evidence of analgesic effects of exposure to comedy, although similar findings are obtained with negative emotions. Few significant correlations have been found between trait measures of humor and immunity, pain tolerance, or self-reported illness symptoms. There is also little evidence of stress-moderating effects of humor on physical health variables and no evidence of increased longevity with greater humor. More rigorous and theoretically informed research is needed before firm conclusions can be drawn about possible health benefits of humor and laughter.


Asunto(s)
Estado de Salud , Inmunidad , Risa/fisiología , Dolor , Ingenio y Humor como Asunto/psicología , Humanos , Risa/psicología , Proyectos de Investigación
18.
J Mol Diagn ; 2(3): 128-31, 2000 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11229516

RESUMEN

The fragile X syndrome is the most commonly inherited cause of mental retardation. Genetic diagnosis of this disease relies on the detection of triplet repeat expansion in the FMR1 gene on the X chromosome. Although the majority of disease in fragile X patients is due to mutations involving triplet repeat expansion, deletion of various portions of FMR1 has also been described in association with the fragile X syndrome. Here we describe a rare polymorphism in the noncoding region of FMR1 that mimics detection of a deletion in a commonly used assay for fragile X syndrome, which can result in misdiagnosis of the disease.


Asunto(s)
Errores Diagnósticos , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/genética , Proteínas del Tejido Nervioso/genética , Polimorfismo Genético , Proteínas de Unión al ARN , Eliminación de Secuencia/genética , Artefactos , Secuencia de Bases , Southern Blotting , Desoxirribonucleasa EcoRI/metabolismo , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Frecuencia de los Genes , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Análisis de Secuencia de ADN
19.
J Med Chem ; 36(7): 888-97, 1993 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-8464043

RESUMEN

In order to prepare GRF analogs with high activity in vivo, a strategy was undertaken to stabilize the peptide to dipeptidylpeptidase IV (DPP-IV), a protease found in plasma which inactivates native human and bovine GRF by cleavage of the Ala2-Asp3 bond. Replacement of the Ala2 residue with Ser, Thr, or Gly in [Leu27]bGRF(1-29)NH2 resulted in peptides greatly stabilized against proteolysis in plasma, but having low inherent GH-releasing activity when tested in bovine pituitary cell cultures. Replacement of Gly15 with Ala15 was marginally effective in improving the in vitro bioactivity of this group of peptides. When tested for GH-hormone release in steers, however, the Thr2,Ala15 analog was four times more potent than bGRF(1-44)NH2. Eleven additional analogs from the [X2,Ala15,Leu27]bGRF(1-29)NH2 series were synthesized and evaluated for metabolic stability in bovine plasma and for GH releasing activity in steers in vivo and in rat pituitary cells in vitro. Two compounds, [Val2,Ala15,Leu27]dGRF(1-29)NH2 and [Ile2,Ala15,Leu27]-bGRF(1-29)NH2, had increased GH-releasing activity in steers over that of [Thr2,Ala15,Leu27]-bGRF(1-29)NH2 and over a previously reported super-potent analog, [desNH2Tyr1,D-Ala2,Ala15]-hGRF(1-29)NH2.


Asunto(s)
Alanina , Hormona Liberadora de Hormona del Crecimiento/análogos & derivados , Animales , Bovinos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Hormona del Crecimiento/sangre , Hormona del Crecimiento/metabolismo , Hormona Liberadora de Hormona del Crecimiento/sangre , Hormona Liberadora de Hormona del Crecimiento/metabolismo , Inyecciones Intravenosas , Masculino , Ratas , Relación Estructura-Actividad
20.
Virus Res ; 45(2): 135-45, 1996 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8896248

RESUMEN

The envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) plays a major role in the down-regulation of its receptor, CD4. This down-regulation, at least in part, is caused by the formation of gp160-CD4 intracellular complexes which fail to transport out of the endoplasmic reticulum (ER). In this report, we have evaluated the ability of envelope glycoproteins from various isolates to block CD4 transport within the endoplasmic reticulum. Using a recombinant vaccinia virus expression system in HeLa cells, we expressed different HIV-1 and HIV-2 envelope glycoproteins with CD4. Pulse-chase labeling followed by immunoprecipitation demonstrated that envelope glycoproteins from primary and lab-adapted isolates were capable of forming intracellular complexes with CD4, resulting in the partial inhibition of CD4 transport to the Golgi. Although the efficiency of CD4 modulation was variable, these differences did not correlate with the type of isolate from which the HIV-1 glycoprotein was derived. However, we did find that the HIV-2 ST envelope glycoprotein (gp150) was not as efficient at blocking CD4 as the glycoprotein (gp140) derived from HIV-2 ROD. The decreased ability of ST gp150 to block CD4 within the ER was associated with an increased efficiency of ST gp150 transport and cleavage. Thus, differences in the ability of HIV envelope glycoproteins to block CD4 transport do exist, and these differences may be determined by envelope glycoprotein transport kinetics.


Asunto(s)
Antígenos CD4/metabolismo , Proteínas gp160 de Envoltorio del VIH/metabolismo , VIH-1/metabolismo , VIH-2/metabolismo , Receptores Virales/metabolismo , Transporte Biológico , Retículo Endoplásmico/metabolismo , Aparato de Golgi/metabolismo , Proteínas gp160 de Envoltorio del VIH/genética , VIH-1/aislamiento & purificación , VIH-2/aislamiento & purificación , Células HeLa , Humanos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo
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