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1.
J Occup Rehabil ; 33(1): 179-188, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35927599

RESUMO

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.


Assuntos
Reabilitação Vocacional , Traumatismos da Medula Espinal , Humanos , Retorno ao Trabalho , Ocupações , Grupos Focais , Traumatismos da Medula Espinal/reabilitação
2.
Phys Occup Ther Pediatr ; 38(5): 510-526, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29236556

RESUMO

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.


Assuntos
Pessoas com Deficiência/reabilitação , Terapia Assistida por Cavalos/métodos , Adolescente , Criança , Feminino , Teoria Fundamentada , Humanos , Masculino , Nova Zelândia , Autoimagem
3.
J Evol Biol ; 29(11): 2256-2265, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27467980

RESUMO

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.


Assuntos
Cor , Melaninas , Odonatos , Territorialidade , Animais , Evolução Biológica , Feminino , Masculino , Asas de Animais
4.
J Evol Biol ; 29(10): 1977-1985, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27316646

RESUMO

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.


Assuntos
Comportamento Materno , Ranidae , Reprodução , Animais , Anuros , Ovos , Larva , Metamorfose Biológica
6.
Nat Genet ; 11(4): 459-61, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7493033

RESUMO

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.


Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 22 , Heterogeneidade Genética , Hipertelorismo/genética , Cromossomo X , Pré-Escolar , Feminino , Ligação Genética , Humanos , Hipospadia/genética , Escore Lod , Masculino , Linhagem , Síndrome
7.
Science ; 167(3924): 1504-6, 1970 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-17750348

RESUMO

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.
Artigo em Inglês | MEDLINE | ID: mdl-19840279

RESUMO

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.


Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Face/anatomia & histologia , Predisposição Genética para Doença , Pais , Estudos de Casos e Controles , Cefalometria , Saúde da Família , Feminino , Humanos , Imageamento Tridimensional , Lábio/anatomia & histologia , Masculino , Desenvolvimento Maxilofacial/genética , Nariz/anatomia & histologia , Órbita/anatomia & histologia , Fotogrametria , Análise de Componente Principal , Fatores Sexuais , Dimensão Vertical , Zigoma/anatomia & histologia
9.
J Mater Sci Mater Med ; 20(4): 883-8, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19083082

RESUMO

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.


Assuntos
Fosfatos de Cálcio/química , Cerâmica , Durapatita/química , Difração de Raios X/métodos , Propriedades de Superfície
10.
J Econ Entomol ; 100(2): 283-90, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17461048

RESUMO

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.


Assuntos
Entomologia/métodos , Insetos/crescimento & desenvolvimento , Animais , Entomologia/economia , Entomologia/instrumentação , Insetos/fisiologia , Larva/crescimento & desenvolvimento , Larva/fisiologia , Controle Biológico de Vetores/economia
11.
Vet Comp Orthop Traumatol ; 19(4): 219-27, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17143394

RESUMO

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.


Assuntos
Lesões do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior/cirurgia , Cães/lesões , Instabilidade Articular/veterinária , Meniscos Tibiais/cirurgia , Joelho de Quadrúpedes/lesões , Joelho de Quadrúpedes/cirurgia , Animais , Ligamento Cruzado Anterior/diagnóstico por imagem , Cães/cirurgia , Feminino , Escala de Gravidade do Ferimento , Instabilidade Articular/diagnóstico por imagem , Instabilidade Articular/epidemiologia , Instabilidade Articular/cirurgia , Coxeadura Animal , Masculino , Maryland/epidemiologia , Linhagem , Complicações Pós-Operatórias/veterinária , Radiografia , Amplitude de Movimento Articular , Estudos Retrospectivos , Joelho de Quadrúpedes/diagnóstico por imagem , Inquéritos e Questionários , Virginia/epidemiologia
12.
Biochim Biophys Acta ; 1164(3): 252-60, 1993 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-8102071

RESUMO

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.


Assuntos
Dipeptidil Peptidases e Tripeptidil Peptidases/metabolismo , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Rim/enzimologia , Serina , Treonina , Valina , Animais , Soluções Tampão , Bovinos , Dipeptidil Peptidase 4 , Dipeptidil Peptidases e Tripeptidil Peptidases/antagonistas & inibidores , Dipeptidil Peptidases e Tripeptidil Peptidases/química , Hormônio Liberador de Hormônio do Crescimento/análogos & derivados , Meia-Vida , Especificidade por Substrato , Suínos
13.
J Nematol ; 37(4): 473-6, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19262893

RESUMO

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.
Artigo em Inglês | MEDLINE | ID: mdl-9464201

RESUMO

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.


Assuntos
Alcoolismo/epidemiologia , Transtornos Relacionados ao Uso de Cocaína/terapia , Transtorno Depressivo/epidemiologia , Adolescente , Adulto , Alcoolismo/diagnóstico , Análise de Variância , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Depressão/diagnóstico , Depressão/epidemiologia , Transtorno Depressivo/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Recidiva , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Centros de Tratamento de Abuso de Substâncias , Resultado do Tratamento
15.
Neurology ; 29(5): 662-9, 1979 May.
Artigo em Inglês | MEDLINE | ID: mdl-571564

RESUMO

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.


Assuntos
Músculos Faciais/fisiopatologia , Paralisia Facial/fisiopatologia , Polirradiculoneuropatia/fisiopatologia , Adulto , Nervo Facial/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Condução Nervosa , Parestesia/fisiopatologia , Nervo Fibular/fisiopatologia , Nervo Tibial/fisiopatologia , Nervo Ulnar/fisiopatologia
16.
Neurology ; 41(10): 1675-6, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1922817

RESUMO

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.


Assuntos
Astrocitoma/fisiopatologia , Neoplasias Encefálicas/fisiopatologia , Bulbo/fisiopatologia , Espirro , Adulto , Astrocitoma/complicações , Neoplasias Encefálicas/complicações , Humanos , Masculino
17.
Psychol Bull ; 127(4): 504-19, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11439709

RESUMO

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.


Assuntos
Nível de Saúde , Imunidade , Riso/fisiologia , Dor , Senso de Humor e Humor como Assunto/psicologia , Humanos , Riso/psicologia , Projetos de Pesquisa
18.
J Mol Diagn ; 2(3): 128-31, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11229516

RESUMO

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.


Assuntos
Erros de Diagnóstico , Síndrome do Cromossomo X Frágil/diagnóstico , Síndrome do Cromossomo X Frágil/genética , Proteínas do Tecido Nervoso/genética , Polimorfismo Genético , Proteínas de Ligação a RNA , Deleção de Sequência/genética , Artefatos , Sequência de Bases , Southern Blotting , Desoxirribonuclease EcoRI/metabolismo , Proteína do X Frágil da Deficiência Intelectual , Frequência do Gene , Humanos , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNA
19.
J Med Chem ; 36(7): 888-97, 1993 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-8464043

RESUMO

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.


Assuntos
Alanina , Hormônio Liberador de Hormônio do Crescimento/análogos & derivados , Animais , Bovinos , Células Cultivadas , Relação Dose-Resposta a Droga , Hormônio do Crescimento/sangue , Hormônio do Crescimento/metabolismo , Hormônio Liberador de Hormônio do Crescimento/sangue , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Injeções Intravenosas , Masculino , Ratos , Relação Estrutura-Atividade
20.
Virus Res ; 45(2): 135-45, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8896248

RESUMO

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.


Assuntos
Antígenos CD4/metabolismo , Proteína gp160 do Envelope de HIV/metabolismo , HIV-1/metabolismo , HIV-2/metabolismo , Receptores Virais/metabolismo , Transporte Biológico , Retículo Endoplasmático/metabolismo , Complexo de Golgi/metabolismo , Proteína gp160 do Envelope de HIV/genética , HIV-1/isolamento & purificação , HIV-2/isolamento & purificação , Células HeLa , Humanos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo
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