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1.
Glob Chang Biol ; 30(1): e16991, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37905464

RESUMO

Sea turtles are vulnerable to climate change since their reproductive output is influenced by incubating temperatures, with warmer temperatures causing lower hatching success and increased feminization of embryos. Their ability to cope with projected increases in ambient temperatures will depend on their capacity to adapt to shifts in climatic regimes. Here, we assessed the extent to which phenological shifts could mitigate impacts from increases in ambient temperatures (from 1.5 to 3°C in air temperatures and from 1.4 to 2.3°C in sea surface temperatures by 2100 at our sites) on four species of sea turtles, under a "middle of the road" scenario (SSP2-4.5). Sand temperatures at sea turtle nesting sites are projected to increase from 0.58 to 4.17°C by 2100 and expected shifts in nesting of 26-43 days earlier will not be sufficient to maintain current incubation temperatures at 7 (29%) of our sites, hatching success rates at 10 (42%) of our sites, with current trends in hatchling sex ratio being able to be maintained at half of the sites. We also calculated the phenological shifts that would be required (both backward for an earlier shift in nesting and forward for a later shift) to keep up with present-day incubation temperatures, hatching success rates, and sex ratios. The required shifts backward in nesting for incubation temperatures ranged from -20 to -191 days, whereas the required shifts forward ranged from +54 to +180 days. However, for half of the sites, no matter the shift the median incubation temperature will always be warmer than the 75th percentile of current ranges. Given that phenological shifts will not be able to ameliorate predicted changes in temperature, hatching success and sex ratio at most sites, turtles may need to use other adaptive responses and/or there is the need to enhance sea turtle resilience to climate warming.


Assuntos
Tartarugas , Animais , Tartarugas/fisiologia , Temperatura , Mudança Climática , Reprodução , Razão de Masculinidade
2.
Bull Environ Contam Toxicol ; 93(5): 536-41, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24957795

RESUMO

This study determined the concentrations of heavy metals in blood collected from Pacific Ridley sea turtles (Lepidochelys olivacea) inhabiting the coast of Guasave, Mexico, in the Gulf of California. The highest reported metal concentration in blood was Zn, followed by Se. Of nonessential toxic metals, As was reported in higher percentage compared to Cd. The concentrations of metals detected were present as follows: Zn > Se > Mn > As > Ni > Cd > Cu. Cd concentration in blood is higher in our population in comparison with other populations of L. olivacea, and even higher in other species of sea turtles. Our study reinforces the usefulness of blood for the monitoring of the levels of contaminating elements, and is easily accessible and nonlethal for sea turtles.


Assuntos
Monitoramento Ambiental , Oligoelementos/sangue , Tartarugas/sangue , Animais , Metais Pesados/sangue , México
3.
Bull Environ Contam Toxicol ; 91(6): 645-51, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24072261

RESUMO

The concentration of heavy metals (Zn, Cd, Ni, Cu, Mn) and selenium (Se) was analyzed in blood collected from 12 black turtles (Chelonia mydas agasiizzi) captured in Canal del Infiernillo, Punta Chueca, Mexico. The most abundant metals were Zn (63.58 µg g(-1)) and Se (7.66 µg g(-1)), and Cd was the lower (0.99 µg g(-1)). The sequential concentrations of trace metals were Zn > Se > Cu > Mn > Ni > Cd. In conclusion, this information is important as a baseline when using blood as tissue analysis of heavy metals; however, these levels could represent recent exposure in foraging grounds of black turtles in the Sea of Cortez.


Assuntos
Monitoramento Ambiental , Metais Pesados/sangue , Selênio/sangue , Tartarugas/sangue , Poluentes Químicos da Água/sangue , Animais , México , Distribuição Tecidual
4.
J Cell Biol ; 111(5 Pt 1): 2149-58, 1990 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-2172262

RESUMO

Smooth muscle cells (SMC) in rat carotid artery leave the quiescent state and proliferate after balloon catheter injury, but the signals for mitogenesis are not known. In this study, the possibility that cells within damaged arteries produce a growth factor that could act locally to stimulate SMC replication and repair was examined. We found that the genes for PDGF-A and -B (ligand) and PDGF receptor (alpha and beta subunits) were expressed in normal and injured carotid arteries and were independently regulated during repair of carotid injury. Two phases of PDGF ligand and receptor gene expression were observed: (a) In the early stage, a large decrease in PDGF beta-receptor mRNA levels preceded 10- to 12-fold increases in PDGF-A transcript abundance in the first 6 h after wounding. No change in PDGF alpha-receptor or PDGF-B gene expression was found at these times. (b) In the chronic phase, 2 wk after injury, neointimal tissue had lower levels of PDGF alpha-receptor mRNA (threefold) and higher levels of PDGF beta-receptor mRNA (three- to fivefold) than did restored media. Moreover, in situ hybridization studies identified a subpopulation of neointimal SMC localized at or near the luminal surface with a different pattern of gene expression than the underlying carotid SMC. Luminal SMC were strongly positive for PDGF-A and PDGF beta-receptor transcripts, while showing little or no hybridization for PDGF-B or PDGF alpha-receptor. Immunohistochemical studies showed strongly positive staining for PDGF-A in SMC along the luminal surface. These data show that changes in PDGF ligand and receptor expression occur at specific times and locations in injured carotid artery and suggest that these changes may play a role in regulating arterial wound repair.


Assuntos
Artérias/lesões , Fator de Crescimento Derivado de Plaquetas/genética , Receptores de Superfície Celular/genética , Animais , Artérias/metabolismo , Lesões das Artérias Carótidas , Regulação da Expressão Gênica , Histonas/genética , Imuno-Histoquímica , Masculino , Hibridização de Ácido Nucleico , Ornitina Descarboxilase/genética , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos , Receptores do Fator de Crescimento Derivado de Plaquetas , Regeneração/genética , Fatores de Tempo , Cicatrização/genética
5.
Science ; 240(4858): 1529-31, 1988 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-2836952

RESUMO

Previous studies involving platelet-derived growth factor (PDGF) have been based on the premise that a single cell-surface receptor binds all three isoforms of PDGF (AA, BB, and AB). It is now shown that two populations of PDGF receptor exist and can be distinguished by their ligand binding specificity. The B receptor binds only the BB dimer, whereas the A/B receptor binds AA, BB, and AB dimers. Human dermal fibroblasts appear to express seven times as much B receptor as A/B receptor. The B receptor is responsible for most PDGF receptor phosphorylation.


Assuntos
Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptores de Superfície Celular/metabolismo , Pele/metabolismo , Ligação Competitiva , Membrana Celular/metabolismo , Células Cultivadas , Fibroblastos/metabolismo , Humanos , Cinética , Receptores do Fator de Crescimento Derivado de Plaquetas , Relação Estrutura-Atividade
6.
Science ; 246(4929): 488-91, 1989 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-2683071

RESUMO

Host cell factors act together with regulatory genes of the human immunodeficiency virus (HIV) to control virus production. Human-Chinese hamster ovary hybrid cell clones were used to probe for human chromosomes involved in regulating HIV gene expression. DNA transfection experiments showed that 4 of 18 clones had high levels of HIV gene expression measured by both extracellular virus production and transactivation of the HIV long terminal repeat in the presence of the trans-activator (tat) gene. Karyotype analyses revealed a 94% concordance (17/18) between human chromosome 12 and HIV gene expression. Other chromosomes had an 11 to 72% concordance with virus production.


Assuntos
Cromossomos Humanos Par 12 , Regulação Viral da Expressão Gênica/genética , HIV-1/genética , Animais , Cloranfenicol O-Acetiltransferase/genética , Cricetinae , Cricetulus , Genes tat , Humanos , Células Híbridas , Sequências Repetitivas de Ácido Nucleico , Ativação Transcricional
7.
PLoS One ; 13(7): e0199825, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30044783

RESUMO

Blood parameters provide an excellent tool to evaluate the health status of wildlife. However, there are few studies about health parameters of sea turtles in Mexico. For olive ridley turtles (Lepidochelys olivacea), no information was available to establish the health baseline for the species. The objective of this study was to establish reference blood biochemistry values for olive ridley turtles in the northern Sinaloa foraging area. Between 2013 and 2015, 82 olive ridley turtles were captured. Body condition index (BCI) presented a mean of 1.46 ± 0.14 (1.17-2.02) that categorized the population with excellent body condition; in addition, 99% of the turtles captured had a good physical appearance. Blood was collected for biochemistry analysis from 60 turtles. Significantly higher values of total protein, albumin, A/G ratio (albumin/globulin) and PCV (packed cell volume or hematocrit) were observed in adult when compared to subadult turtles. On the other hand, no significant differences were found when females and males were compared. Based on the BCI, physical assessment, and blood parameters, and compared to other sea turtle species, olive ridley turtles in northern Sinaloa were considered in excellent health. To the best of our knowledge, this is the first study to establish normal blood biochemistry values of foraging olive ridley turtles in northern Sinaloa.


Assuntos
Tartarugas/sangue , Animais , Proteínas Sanguíneas/análise , Feminino , Hematócrito , Masculino , México
8.
J Clin Invest ; 84(3): 1036-40, 1989 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2760210

RESUMO

Fibroplasia and angiogenesis are essential components of tissue repair when substantial tissue has been lost at a site of injury. Platelets and monocyte/macrophages accumulate at these sites and release a variety of growth factors that are thought to initiate and sustain the repair. Often the involved tissue contracts, a process that can markedly reduce the amount of fibroplasia and angiogenesis necessary for the reestablishment of organ integrity. Such tissue contraction occurs over hours or days, a much slower time course than the rapid, reversible contraction of muscle tissue. Fibroblasts, which are rich in f-actin bundles, appear to be responsible for wound contraction. However, the signals that stimulate contraction are not known. Using cultured fibroblasts, which are also rich in f-actin bundles, we demonstrate the platelet and monocyte isoforms of platelet-derived growth factor (PDGF; AB and BB) but not PDGF-AA, can stimulate fibroblasts to contract collagen matrix in a time course similar to that of wound contraction. In addition, PDGF appears to be the predominant fibroblast/collagen gel contraction activity released from platelets. Vasoactive agonists known to stimulate smooth and striated muscle contraction do not stimulate fibroblast-driven collagen gel contraction.


Assuntos
Colágeno/fisiologia , Matriz Extracelular/imunologia , Fibroblastos/fisiologia , Fator de Crescimento Derivado de Plaquetas/fisiologia , Citoesqueleto de Actina/fisiologia , Células Cultivadas , Tecido Conjuntivo/fisiologia , Géis , Humanos , Fator de Crescimento Derivado de Plaquetas/análogos & derivados , Proteínas Recombinantes/farmacologia
9.
J Clin Invest ; 92(2): 671-8, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8349805

RESUMO

PDGF has been implicated as one of the principal mitogens involved in cutaneous wound healing. While it has been previously reported that both platelets and monocytes are a source of PDGF in human dermal wound repair, the production of PDGF by human keratinocytes has not yet been described. In this manuscript, we report the production of PDGF by cultured human keratinocytes. Both PDGF A and B chain mRNA can be detected in cultured cells. While only PDGF-AA polypeptide is found in significant levels in keratinocyte-conditioned culture media, all three PDGF isoforms (AA, AB, and BB) are present in detergent-solubilized cell extracts. No evidence of PDGF receptor expression was observed in cultured keratinocytes when analyzed for either mRNA levels or polypeptide expression, suggesting that PDGF does not play an autocrine role in keratinocyte growth. Analysis of cryosections of human cutaneous wounds by immunostaining for PDGF showed that both PDGF A and B chain is constitutively expressed in normal epidermis, as well as in newly reconstituted wound epidermis. No evidence for PDGF receptor polypeptide expression in the epidermis was detected by immunostaining of cryosections.


Assuntos
Queratinócitos/metabolismo , Fator de Crescimento Derivado de Plaquetas/biossíntese , Pele/metabolismo , Ferimentos e Lesões/fisiopatologia , Anticorpos Monoclonais , Biópsia , Células Cultivadas , Meios de Cultivo Condicionados , Ensaio de Imunoadsorção Enzimática , Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Imuno-Histoquímica , Recém-Nascido , Cinética , Substâncias Macromoleculares , Masculino , Fator de Crescimento Derivado de Plaquetas/análise , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Receptores do Fator de Crescimento Derivado de Plaquetas/análise , Receptores do Fator de Crescimento Derivado de Plaquetas/biossíntese , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo , Ferimentos e Lesões/patologia
10.
J Clin Invest ; 92(1): 338-48, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8326002

RESUMO

Healing baboon polytetrafluoroethylene grafts express PDGF mRNA in the neointima. Perfusates of graft segments also contain PDGF-like mitogenic activity. To extend these findings, we studied the expression and regional distribution of the PDGF protein isoforms and their receptors in this prosthetic graft model. By immunohistochemistry, as well as ELISA and Western blot analysis of tissue extracts, both PDGF-A and PDGF-B were identified in macrophages within the interstices of the synthetic material. In contrast, the neointima contained predominantly PDGF-A localized to the endothelial surface and the immediate subjacent smooth muscle cell layers. Tissue extracts of neointima and graft material were mitogenic for baboon aortic smooth muscle cells in culture; nearly all of this proliferative activity was blocked by a neutralizing anti-PDGF antibody. PDGF receptor beta-subunit mRNA and protein were easily detectable in the neointima and graft material. PDGF receptor alpha-subunit mRNA was also observed in the graft matrix and at lower levels in the neointima. This pattern of ligand and receptor expression further implicates locally produced PDGF as a regulator of neointimal smooth muscle cell growth in this model. The coexpression of ligand and receptor in the macrophage-rich matrix also suggests that PDGF may participate in the foreign body response.


Assuntos
Prótese Vascular , Músculo Liso Vascular/citologia , Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo , Animais , Divisão Celular , Matriz Extracelular/metabolismo , Reação a Corpo Estranho , Expressão Gênica , Hibridização In Situ , Músculo Liso Vascular/metabolismo , Papio , Politetrafluoretileno , RNA Mensageiro/genética
11.
Circ Res ; 86(7): 779-86, 2000 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-10764412

RESUMO

The growth of neointima and neointimal smooth muscle cells in baboon polytetrafluoroethylene grafts is regulated by blood flow. Because neointimal smooth muscle cells express both platelet-derived growth factor receptor-alpha and -beta (PDGFR-alpha and -beta), we designed this study to test the hypothesis that inhibiting either PDGFR-alpha or PDGFR-beta with a specific mouse/human chimeric antibody will modulate flow-induced neointimal formation. Bilateral aortoiliac grafts and distal femoral arteriovenous fistulae were placed in 17 baboons. After 8 weeks, 1 arteriovenous fistulae was ligated, normalizing flow through the ipsilateral graft while maintaining high flow in the contralateral graft. The experimental groups received a blocking antibody to PDGFR-alpha (Ab-PDGFR-alpha; 10 mg/kg; n=5) or PDGFR-beta (Ab-PDGFR-beta; 10 mg/kg; n=6) by pulsed intravenous administration 30 minutes before ligation and at 4, 8, 15, and 22 days after ligation. Controls received carrier medium alone (n=8). Serum antibody concentrations were followed. Grafts were harvested after 28 days and analyzed by videomorphometry. Serum Ab-PDGFR-alpha concentrations fell rapidly after day 7 to 0, whereas serum Ab-PDGFR-beta concentrations were maintained at the target levels (>50 microg/mL). Compared with controls (3.7+/-0.3), the ratio of the intimal areas (normalized flow/high flow) was significantly reduced in Ab-PDGFR-beta (1.2+/-0.2, P<0.01) but not in Ab-PDGFR-alpha (2.2+/-0.4). Ab-PDGFR-alpha decreased significantly the overall smooth muscle cell nuclear density of the neointima (P<0.01) compared with either the control or Ab-PDGFR-beta treated groups. PDGFR-beta is necessary for flow-induced neointimal formation in prosthetic grafts. Targeting PDGFR-beta may be an effective pharmacological strategy for suppressing graft neointimal development.


Assuntos
Endotélio Vascular/fisiologia , Músculo Liso Vascular/fisiologia , Neovascularização Patológica , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/fisiologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/fisiologia , Túnica Íntima/fisiologia , Animais , Anticorpos/farmacologia , Aorta/cirurgia , Apoptose , Derivação Arteriovenosa Cirúrgica , Velocidade do Fluxo Sanguíneo , Divisão Celular , Células Cultivadas , Quimiotaxia/efeitos dos fármacos , Quimiotaxia/fisiologia , Endotélio Vascular/citologia , Endotélio Vascular/transplante , Artéria Femoral/cirurgia , Veia Femoral/cirurgia , Humanos , Hiperplasia , Artéria Ilíaca/cirurgia , Masculino , Camundongos , Músculo Liso Vascular/citologia , Músculo Liso Vascular/transplante , Papio , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Receptor beta de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Proteínas Recombinantes de Fusão/farmacologia , Estresse Mecânico , Túnica Íntima/citologia , Túnica Íntima/patologia
12.
Cancer Res ; 50(19): 6344-8, 1990 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-2169345

RESUMO

The distribution of the beta-subunit of platelet-derived growth factor receptor (PDGFR-beta) was assessed by a sensitive immunoalkaline phosphatase technique using the monoclonal antibody PR7212. Frozen tissue sections of several nonneoplastic human tissues were stained along with 42 soft tissue sarcomas, 16 benign soft tissue proliferations, and 7 epithelial tumors. In all nonneoplastic tissue, there was intense labeling of cell processes of perivascular fibroblasts or pericytes in and about the walls of muscular blood vessels and of fibroblast cell processes around some glandular and ductal epithelia. No PDGFR-beta was found in the endothelial cells of muscular arteries and veins, but cells of uncertain identity within some capillaries were immunoreactive and the possibility that endothelial cells of some small capillaries express PDGFR-beta could not be excluded. In kidney there was strong labeling of glomerular mesangial cells and interstitial fibroblasts. Some histological types of soft tissue sarcomas were uniformly and strongly labeled with anti-PDGFR-beta, but other types were infrequently labeled or unreactive. The order of decreasing frequency and strength of labeling of the various types of benign and malignant soft tissue proliferations was as follows: benign fibromatosis and neurofibroma greater than malignant fibrous histiocytoma greater than liposarcoma greater than leiomyosarcoma greater than rhabdomyosarcoma. No tumor cell labeling was detected in epithelioid, synovial or clear cell sarcomas, leiomyomas, or carcinomas, but there was usually strong labeling of fibroblast and/or pericyte cell processes within tumor, especially around blood vessels. We conclude that PDGFR-beta is strongly expressed by vascular and stromal tissues of most tumors and normal organs and by tumor cells of several types of soft tissue tumors and proliferations, most notably those of fibroblastic origin.


Assuntos
Vasos Sanguíneos/análise , Receptores de Superfície Celular/análise , Neoplasias de Tecidos Moles/análise , Membrana Celular/análise , Feminino , Fibroblastos/análise , Humanos , Masculino , Músculo Liso Vascular/análise , Receptores do Fator de Crescimento Derivado de Plaquetas
13.
Circulation ; 101(22): 2651-7, 2000 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-10840019

RESUMO

BACKGROUND: Tissue factor located in the atherosclerotic plaque might cause the clinically significant thrombotic events associated with end-stage disease. It might also affect intimal area by increasing matrix accumulation and stimulating smooth muscle cell (SMC) migration and proliferation. To test this hypothesis, we overexpressed tissue factor in a rat model of the human fibrous plaque. METHODS AND RESULTS: A neointima was generated by seeding tissue factor-overexpressing rat SMCs onto the luminal surface of a balloon-injured syngeneic rat carotid artery. The cells attached and expressed tissue factor over the long term. Mural thrombus accumulation was present at 4 and 7 days and increased neointimal SMC numbers and area by 2-fold at 2 and 4 weeks. Tissue factor overexpression accelerated reendothelialization compared with controls at 2 weeks and 1 month. Tissue factor-overexpressing SMCs exhibited increased migration both in vitro and in vivo. The increased migration by tissue factor-overexpressing SMCs in vitro was not dependent on activation of the coagulation cascade and could be blocked by an inhibitor of tissue factor. CONCLUSIONS: These results suggest that tissue factor plays a direct role in neointimal development by coagulation-dependent and -independent pathways.


Assuntos
Arteriosclerose/patologia , Lesões das Artérias Carótidas/patologia , Tromboplastina/genética , Trombose/patologia , Animais , Arteriosclerose/metabolismo , Coagulação Sanguínea , Plaquetas/citologia , Northern Blotting , Cateterismo/efeitos adversos , Movimento Celular/fisiologia , Células Cultivadas , Endotélio Vascular/patologia , Endotélio Vascular/ultraestrutura , Fator VIIa/metabolismo , Expressão Gênica/fisiologia , Masculino , Microscopia Eletrônica de Varredura , Músculo Liso Vascular/citologia , Músculo Liso Vascular/fisiologia , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos F344 , Tromboplastina/metabolismo , Trombose/metabolismo , Túnica Íntima/patologia , Túnica Íntima/ultraestrutura
14.
J Am Coll Cardiol ; 28(7): 1858-65, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8962577

RESUMO

OBJECTIVES: We determined the effect of adjunctive inhibition of the extrinsic coagulation pathway by factor VIIa-tissue factor complex inhibitors, DEGR VIIa and tissue factor pathway inhibitor (TFPI), and the selective factor Xa inhibitor, tick anticoagulant peptide (TAP), after thrombolytic therapy with tissue-type plasminogen activator (t-PA) in a canine model of electrically induced coronary thrombosis. BACKGROUND: Ongoing thrombin generation is considered an important component of the heightened thrombin activity associated with thrombolytic therapy and may be responsible for reperfusion failure and reocclusion. METHODS: Forty-two dogs with electrically induced coronary thrombus undergoing thrombolysis with t-PA (1 mg/kg over 20 min) were randomly assigned to one of the following adjunctive regimens: TAP (30 micrograms/kg body weight per min for 90 min, n = 10); TFPI (100 to 150 micrograms/kg per min for 90 min, n = 10); DEGR VIIa (1- to 2-mg/kg bolus, n = 10) and saline control (n = 12). The dogs were observed for 120 min after thrombolysis for reocclusion. RESULTS: All three active study agents accelerated the time to reperfusion by an average of 12 min (all p < 0.05). Duration of reflow was greatest with TAP (117 +/- 8 min, p < 0.05 compared with saline control), whereas DEGR VIIa and TFPI did not prolong the duration of reflow. Reocclusion rates were similar among control, DEGR VIIa and TFPI groups (70%, 78% and 67%, respectively). Tick anticoagulant peptide reduced the occurrence of reocclusion (0%, p < 0.05 compared with saline control). CONCLUSIONS: In this experimental model, during systematic blockade of various extrinsic coagulation pathway proteins, we demonstrated that whereas acceleration of thrombolysis occurs with factor VIIa-tissue factor complex inhibition, optimal enhancement of thrombolysis was achieved through specific factor Xa blockade.


Assuntos
Trombose Coronária/tratamento farmacológico , Inibidores do Fator Xa , Lipoproteínas/uso terapêutico , Peptídeos/uso terapêutico , Terapia Trombolítica , Animais , Proteínas de Artrópodes , Coagulação Sanguínea/efeitos dos fármacos , Trombose Coronária/sangue , Trombose Coronária/fisiopatologia , Cães , Fator VIIa/antagonistas & inibidores , Fator Xa/fisiologia , Hemostasia/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular , Lipoproteínas/sangue , Tromboplastina/antagonistas & inibidores , Ativador de Plasminogênio Tecidual/uso terapêutico
15.
Mol Genet Metab Rep ; 4: 49-52, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26937410

RESUMO

Maple syrup urine disease is caused by a deficiency in the branched chain ketoacid dehydrogenase (BCKAD) complex. This results in the accumulation of branched chain amino acids (BCAA) and branched chain ketoacids in the body. Even when aggressively treated with dietary restriction of BCAA, patients experience long term cognitive, neurological and psychosocial problems. Liver transplantation from deceased donors has been shown to be an effective modality in introducing adequate BCKAD activity, attaining a metabolic cure for patients. Here, we report the clinical course of the first known patient with classic MSUD who received two consecutive partial liver grafts from two different living non-carrier donors and his five year outcome posttransplant. We also show that despite the failure of the first liver graft, and initial acute cellular rejection of the second liver graft in our patient, his metabolic control remained good without metabolic decompensation.

16.
AIDS ; 15(7): 837-45, 2001 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-11399956

RESUMO

OBJECTIVE: To describe initial viral dissemination to peripheral tissues and infectious body fluids during human primary HIV infection. DESIGN: Observational cohort study. METHODS: Blood plasma, cerebrospinal fluid (CSF), seminal plasma, cervicovaginal lavage fluid and/or saliva were sampled from 17 individuals with primary HIV infection (range of time from symptoms onset to sampling, 8--70 days) and one individual with early infection (168 days). Subjects' HIV-1 RNA levels in each fluid were compared with levels from antiretroviral-naive controls with established HIV infection. For study subjects, correlations were assessed between HIV-1 RNA levels and time from symptoms onset. Responses to antiretroviral therapy with didanosine + stavudine + nevirapine +/- hydroxyurea were assessed in each compartment. RESULTS: HIV-1 RNA levels were highest closest to symptoms onset in blood plasma (18 patients) and saliva (11 patients). CSF HIV-1 RNA levels (five patients) appeared lower closer to symptoms onset, although they were higher overall in primary versus established infection. Shedding into seminal plasma (eight patients) and cervicovaginal fluid (two patients) was established at levels observed in chronic infection within 3--5 weeks of symptoms onset. High-level seminal plasma shedding was associated with coinfection with other sexually transmitted pathogens. Virus replication was suppressed in all compartments by antiretroviral therapy. CONCLUSIONS: Peak level HIV replication is established in blood, oropharyngeal tissues and genital tract, but potentially not in CSF, by the time patients are commonly diagnosed with primary HIV infection. Antiretroviral therapy is unlikely to limit initial virus spread to most tissue compartments, but may control genital tract shedding and central nervous system expansion in primary infection.


Assuntos
Líquidos Corporais/virologia , Infecções por HIV/virologia , HIV-1/fisiologia , Fármacos Anti-HIV/uso terapêutico , Estudos de Coortes , Infecções por HIV/tratamento farmacológico , Infecções por HIV/fisiopatologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Saúde Pública , RNA Viral/análise , RNA Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
17.
J Invest Dermatol ; 94(6 Suppl): 53S-57S, 1990 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2161888

RESUMO

Platelet-derived growth factor (PDGF) has been identified as a major mitogen in serum for cultured cells of mesenchymal origin. PDGF was first identified in and purified from human platelet sources. PDGF from platelets is composed of two chains, A-chains and B-chains, which share 60% sequence identity and which can dimerize to form the three combinations PDGF-AA, PDGF-BB, and PDGF-AB. All three dimer forms of PDGF have been isolated from natural sources. Initial studies involving PDGF were based upon the existence of a single cell-surface receptor for PDGF. It has recently been demonstrated that there are two PDGF-receptor subunits, termed alpha and beta, which can associate as three dimer forms (alpha/alpha, alpha/beta, beta/beta) with variable binding specificity for the PDGF ligand dimers. cDNA clones have been obtained for both of the receptor subunits and were shown to code for similar proteins belonging to the split tyrosine kinase family of receptors. The current model of the PDGF receptor subunits proposes that high-affinity binding sites require dimerization of the subunits and that dimerization is associated with activation of the tyrosine kinase of the receptors. The total number of the two receptor subunits and ratio expressed varies between cell types and appears to account for the variable responsiveness of different cell types to the three dimer forms of PDGF.


Assuntos
Receptores de Superfície Celular/metabolismo , Sequência de Aminoácidos , Animais , Fenômenos Químicos , Química , DNA/genética , Humanos , Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptores de Superfície Celular/genética , Receptores do Fator de Crescimento Derivado de Plaquetas , Distribuição Tecidual
18.
J Invest Dermatol ; 96(6): 983-6, 1991 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-1646268

RESUMO

Platelet-derived growth factor (PDGF) is a potent mitogenic and chemotactic factor for fibroblasts and other cell types. PDGF effects are mediated by binding of PDGF to dimeric PDGF receptors possessing intrinsic tyrosine kinase activity. We examined the expression pattern of PDGF receptors in cryostat sections of normal and growth-activated human skin using a monoclonal antibody, PR7212, specific for the beta subunit of the PDGF receptor. PDGF receptors were expressed at low levels in normal skin, with only occasional staining of dermal connective tissue cells. In contrast, PDGF receptor expression was greatly elevated in the dermis of growth-activated skin from 15 chronic wounds and 10 psoriatic lesions. PDGF receptors were increased in dermal fibroblasts and in dermal blood vessels in both conditions. Immunoblot analysis confirmed the increased expression of beta-subtype PDGF receptors in psoriatic lesional tissue. PDGF receptors were not detected in normal or growth-activated epidermis. Differential expression of PDGF receptors could regulate increased proliferation of vascular and connective tissue cells observed in psoriasis and chronic wounds.


Assuntos
Fator de Crescimento Derivado de Plaquetas , Psoríase/metabolismo , Receptores de Superfície Celular/metabolismo , Pele/metabolismo , Ferimentos e Lesões/metabolismo , Anticorpos Monoclonais , Western Blotting , Humanos , Imuno-Histoquímica , Receptores do Fator de Crescimento Derivado de Plaquetas , Pele/lesões
19.
J Comp Neurol ; 239(2): 155-62, 1985 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-2413090

RESUMO

The cytochemical properties of intracellular membrane systems which are likely to be subcellular sites of glycoprotein oligosaccharide synthesis and trafficking have been compared in cultured neuroblastoma cells (as a potential model system) and in Purkinje neurons of rat cerebellum. In aldehyde-fixed N18 cells, permeabilized with Triton X-100, concanavalin A (Con A) binding sites were found in the somata, neurites, and growth cones. Con A binding sites in growth cones appeared as a fine, membranous network. Wheat germ agglutinin (WGA) binding sites were restricted to the perinuclear region of the soma and to the distal tips of growing neurites. As shown previously, Purkinje cell somata and presynaptic terminals also contain Con A binding sites. In this study, WGA and succinylated WGA binding sites were observed in the presynaptic terminals of Purkinje cells. Neuraminidase enzyme digestion prior to lectin labeling removed or greatly reduced WGA binding in the neuropil of the deep nucleus but not in presynaptic terminals of Purkinje cells. Succinylated WGA binding sites were not affected by neuraminidase digestion. Neuraminidase digestion also exposed Ricinis communis agglutinin I binding sites in the neuropil and in synaptic terminals of Purkinje cells. These results in combination with previous studies of intracellular lectin cytochemistry of neurons in the central nervous system demonstrate the similarity of these cells to neuroblastoma cells in their intracellular lectin binding characteristics. Results of the lectin cytochemical studies after neuraminidase digestion of presynaptic terminals support the possibility that neurons may use a post- or extra-Golgi system for the addition of peripheral sugars to the oligosaccharides of certain glycoproteins destined for the cell surface.


Assuntos
Lectinas/metabolismo , Neurônios/metabolismo , Oligossacarídeos/biossíntese , Animais , Transporte Axonal , Sítios de Ligação , Cerebelo/metabolismo , Glicoproteínas/metabolismo , Histocitoquímica , Masculino , Camundongos , Ratos , Ratos Endogâmicos
20.
Biotechniques ; 24(5): 810-6, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9591131

RESUMO

We have developed a quantitative competitive PCR (QC-PCR) assay in a microplate format for quantifying human immunodeficiency virus Type 1 (HIV-1) DNA or RNA in a broad range of source materials. Our QC-PCR assay is a modification of technique originally described by Piatak et al. (1993), which is based on the presence of a competitive internal standard containing an internal 80-bp deletion of HIV-1 gag target sequence. For improved detection and quantification of the wild-type and internal-standard PCR products in a microplate format, we introduced a non-HIV, 31-bp insert into the internal standard as a probe hybridization site that does not cross-hybridize with wild-type HIV-1 products. By using a primer pair in which one primer is biotinylated, QC-PCRs can be bound to a streptavidin-coated microplate, denatured and probed with a digoxigenin (Dig)-labeled, wild-type or internal-standard probe. The hybridized Dig-labeled probes are detected with an anti-Dig antibody conjugated to detector molecules for luminometry (aequorin) or optical densitometry (peroxidase), yielding results that are quantifiable over the range of 100-10,000 copies of HIV gag. Tested source materials for HIV-1 DNA or RNA quantification include plasma, vaginal lavage and cultured cells. The application of the QC-PCR assay using the microplate format affords a convenient and cost-effective method for quantifying HIV-1 proviral and viral loads from a variety of body fluids, cells and tissues.


Assuntos
HIV-1/genética , HIV-1/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Equorina , DNA Viral/análise , DNA Viral/sangue , Digoxigenina , Feminino , Infecções por HIV/sangue , Infecções por HIV/virologia , HIV-1/química , Humanos , Sondas de Oligonucleotídeos , Peroxidase , Reação em Cadeia da Polimerase/instrumentação , Reação em Cadeia da Polimerase/normas , RNA Viral/análise , RNA Viral/sangue , Irrigação Terapêutica , Vagina/química
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