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1.
J Gen Virol ; 97(1): 110-120, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26585962

RESUMO

A full-length genome sequence of 27,739  nt was determined for the only known European turkey coronavirus (TCoV) isolate. In general, the order, number and size of ORFs were consistent with other gammacoronaviruses. Three points of recombination were predicted, one towards the end of 1a, a second in 1b just upstream of S and a third in 3b. Phylogenetic analysis of the four regions defined by these three points supported the previous notion that European and American viruses do indeed have different evolutionary pathways. Very close relationships were revealed between the European TCoV and the European guinea fowl coronavirus in all regions except one, and both were shown to be closely related to the European infectious bronchitis virus (IBV) Italy 2005. None of these regions of sequence grouped European and American TCoVs. The region of sequence containing the S gene was unique in grouping all turkey and guinea fowl coronaviruses together, separating them from IBVs. Interestingly the French guinea fowl virus was more closely related to the North American viruses. These data demonstrate that European turkey and guinea fowl coronaviruses share a common genetic backbone (most likely an ancestor of IBV Italy 2005) and suggest that this recombined in two separate events with different, yet related, unknown avian coronaviruses, acquiring their S-3a genes. The data also showed that the North American viruses do not share a common backbone with European turkey and guinea fowl viruses; however, they do share similar S-3a genes with guinea fowl virus.


Assuntos
Coronavirus do Peru/classificação , Coronavirus do Peru/genética , Evolução Molecular , Genoma Viral , RNA Viral/genética , Recombinação Genética , Análise de Sequência de DNA , Animais , Análise por Conglomerados , Coronavirus do Peru/isolamento & purificação , Ordem dos Genes , Genótipo , Dados de Sequência Molecular , Filogenia , Homologia de Sequência , Sintenia , Perus
2.
Eur J Vasc Endovasc Surg ; 44(5): 491-7, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22975154

RESUMO

OBJECTIVE: To compare differences in macrophage heterogeneity and morphological composition between atherosclerotic plaques obtained from recently symptomatic patients with carotid artery disease and femoral plaques from patients with severe limb ischemia. DESIGN: Experimental study. METHODS: Plaques were obtained from 32 patients undergoing carotid endarterectomy and 25 patients undergoing common femoral endarterectomy or lower limb bypass. Macrophages and T cell numbers were detected in plaque sections by immunohistochemistry and anti CD68 and CD3 antibodies. Dual staining for CD68 and M1- and M2-macrophage markers and morphometric analysis of hematoxylin and eosin stained plaque sections was performed. RESULTS: Carotid plaques had significantly increased percentage areas of confluent lipid and leukocytic infiltrates. In contrast, areas of fibroconnective tissue were significantly greater in femoral plaques and percentage areas of confluent calcification and collagen were elevated. Carotid artery plaques had greater numbers per plaque area of macrophages and T cells consistent with a more inflammatory phenotype. Proportions displaying M1-activation markers were significantly increased in the carotid compared to femoral plaques whereas femoral plaques displayed a greater proportion of M2-macrophages. CONCLUSION: Plaques from patients with recently symptomatic carotid disease have a predominance of M1-macrophages and higher lipid content than femoral plaques, consistent with a more unstable plaque.


Assuntos
Aterosclerose/imunologia , Artérias Carótidas/imunologia , Doenças das Artérias Carótidas/imunologia , Artéria Femoral/imunologia , Macrófagos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Aterosclerose/patologia , Aterosclerose/cirurgia , Biomarcadores/análise , Complexo CD3/análise , Artérias Carótidas/patologia , Artérias Carótidas/cirurgia , Doenças das Artérias Carótidas/patologia , Doenças das Artérias Carótidas/cirurgia , Constrição Patológica , Feminino , Artéria Femoral/patologia , Artéria Femoral/cirurgia , Humanos , Imuno-Histoquímica , Macrófagos/classificação , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Placa Aterosclerótica , Escócia , Linfócitos T/imunologia
3.
J Cell Biol ; 101(4): 1492-500, 1985 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-2864347

RESUMO

To determine the contribution of microtubules to a hypothetical intracellular matrix, we have analyzed the space occupied by microtubules in vitro. Taxol-stabilized microtubules assembled from purified (three-times-cycled) bovine brain microtubule protein were pelleted by centrifugation under standardized conditions. The specific volume of the pellet, defined as the microliter volume per milligram protein, was 22.4. As suggested by others, this volume was strongly dependent on microtubule-associated proteins (MAPs), as shown by quantitation of the effects of purified MAP supplementation on specific volume. The specific volumes of microtubule pellets stripped of MAPs by high salt or chymotryptic digestion approached the mathematically optimal (least occupied space) and increased 14-fold with the highest MAP concentrations employed. Packing was also dependent on pH. Specific volumes comparable to those of MAP-depleted microtubules were attainable at pH's from 5.5 to 6.0, and specific volumes more than doubled at pH 7.5. MAP content was unaffected by pH. We present a theoretical analysis that suggests that as microtubules are centrifuged the mixture behaves as a liquid crystal. With packing, the mixture undergoes an isotropic-nematic phase transition in which the microtubules become oriented principally as parallel rods, mimicking their orientation in vivo. From the known concentration of microtubules in vivo, it can be inferred from our measurements that in some cells a large fraction, perhaps 40-50% of the cytosolic volume, is occupied by microtubules that form a mechanically irreducible space. Further theoretical analysis employing Ogston's formulation of the penetrability of fibrous networks suggests that the space between microtubules (in contrast to the extracellular matrix) imposes little barrier to the diffusion of macromolecules. A microtubule array thus achieves mechanical stability without affecting transport by diffusion. The space can accommodate other fibrous networks that could then affect transport, and, as we show, the space itself may be regulated by MAP content and intracellular pH.


Assuntos
Citoesqueleto/ultraestrutura , Microtúbulos/ultraestrutura , Alcaloides , Animais , Química Encefálica , Bovinos , Centrifugação , Cristalização , Concentração de Íons de Hidrogênio , Matemática , Microscopia Eletrônica , Proteínas Associadas aos Microtúbulos/análise , Paclitaxel , Viscosidade
4.
J Cell Biol ; 101(3): 1086-93, 1985 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-4040916

RESUMO

[35S]Sulfate incorporation was measured in populations of Chinese hamster ovary cells enriched for mitotics, early G1 cells, and interphase monolayers or suspensions. Incorporation was determined by biochemical analysis of extracts and quantitative autoradiography of thick sections. 90% of [35S]sulfate was incorporated into glycosaminoglycan (GAG). Incorporation was depressed fourfold in mitotics and stimulated by from two- to three-fold in early G1 cells relative to mixed interphase cells. GAG synthesis was maintained into late G2. Thus, the rate of GAG biosynthesis was correlated temporally with the detachment and reattachment of cells to substrate. Inhibitors of protein synthesis brought about the rapid arrest of GAG biosynthesis. However, xylosides, which bypass the requirement for core protein, did not bring oligosaccharide sulfation in mitotics to interphase levels. These observations indicate an inhibition of Golgi processing and are consistent with a generalized defect of membrane vesicle-mediated transport during mitosis.


Assuntos
Glicosaminoglicanos/biossíntese , Interfase , Mitose , Animais , Adesão Celular , Linhagem Celular , Cricetinae , Cricetulus , Feminino , Glicosídeos/farmacologia , Cobaias , Ovário , Biossíntese de Proteínas , Sulfatos/metabolismo
5.
Virology ; 526: 138-145, 2019 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-30388629

RESUMO

Subgroup C Avian Metapneumoviruses (AMPV-C) has two lineages, one mostly in turkeys and one mostly in ducks. To investigate the molecular basis of AMPV-C host tropism, a reverse genetics system for a duck AMPV-C virus was developed. A recombinant copy and a recombinant virus in which the SH protein had been exchanged for that of a turkey AMPV-C were rescued. No change in cytopathogenic effect or replication profile in vitro were observed for either virus compared to the wild type. In SPF Muscovy ducks the wild type and its recombinant copy were equally pathogenic. Exchanging the SH in the recombinant copy produced the same results. In SPF turkeys, neither recombinant virus was pathogenic, although both showed a low level of replication. Thus, from the current model, it appears that AMPV-C SH proteins derived from the different species are compatible and that turkey SH does not affect duck AMPV-C pathogenicity.


Assuntos
Metapneumovirus/fisiologia , Infecções por Paramyxoviridae/veterinária , Doenças das Aves Domésticas/virologia , Vírus Reordenados/fisiologia , Proteínas Virais/metabolismo , Tropismo Viral/genética , Animais , Efeito Citopatogênico Viral , Patos , Metapneumovirus/genética , Metapneumovirus/patogenicidade , Infecções por Paramyxoviridae/virologia , Vírus Reordenados/genética , Vírus Reordenados/patogenicidade , Genética Reversa , Perus , Proteínas Virais/genética , Replicação Viral
6.
J Virol Methods ; 251: 61-68, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29030071

RESUMO

Current molecular methods for the detection of avian and human metapneumovirus (AMPV, HMPV) are specifically targeted towards each virus species or individual subgroups of these. Here a broad range SYBR Green I real time RT-PCR was developed which amplified a highly conserved fragment of sequence in the N open reading frame. This method was sufficiently efficient and specific in detecting all MPVs. Its validation according to the NF U47-600 norm for the four AMPV subgroups estimated low limits of detection between 1000 and 10copies/µL, similar with detection levels described previously for real time RT-PCRs targeting specific subgroups. RNA viruses present a challenge for the design of durable molecular diagnostic test due to the rate of change in their genome sequences which can vary substantially in different areas and over time. The fact that the regions of sequence for primer hybridization in the described method have remained sufficiently conserved since the AMPV and HMPV diverged, should give the best chance of continued detection of current subgroups and of potential unknown or future emerging MPV strains.


Assuntos
Metapneumovirus/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Animais , Benzotiazóis , Aves , Diaminas , Humanos , Compostos Orgânicos/metabolismo , Quinolinas , Sensibilidade e Especificidade , Coloração e Rotulagem/métodos , Fatores de Tempo
7.
Kidney Int Suppl ; (103): S38-43, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17080110

RESUMO

Since 2000, the Ottawa Hospital Home Dialysis Program has used a variation on the embedded peritoneal dialysis catheter technique described by Moncrief et al. In this paper, we describe our approach to placement of peritoneal access and report our experience with 304 embedded catheters placed between January 2000 and December 2003. We review the advantages and disadvantages of this technique and describe factors that have been important to the success of our program.


Assuntos
Cateterismo/métodos , Cateteres de Demora , Hemodiálise no Domicílio/instrumentação , Falência Renal Crônica/terapia , Diálise Peritoneal/instrumentação , Humanos , Ontário , Ambulatório Hospitalar/organização & administração , Avaliação de Programas e Projetos de Saúde
8.
Exp Hematol ; 17(9): 929-34, 1989 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-2776854

RESUMO

Tumor recurrence and regimen-related toxicity remain major obstacles in the successful use of marrow transplantation as therapy for hematologic malignancies. By attaching radionuclides to monoclonal antibodies (MoAbs) targeted at myeloid-associated antigenic determinants, a more effective and directed delivery of therapy may be possible without increasing toxicity. We investigated the biodistribution over time of an anti-myeloid antibody (DM-5) labeled with trace amounts of 131I in normal dogs. This study demonstrates the ability to target marrow with a high degree of selectivity, achieving marrow/blood ratios of 25-30:1 with the greatest concentration in any other organ being a tissue/blood ratio of 1.4:1 for stomach at 48 h. A pretreatment dose of unlabeled antibody effectively reduced early hepatic uptake by 80%, resulting in improved marrow localization with an estimated 58.6% of the injected dose localized in marrow within 2 h following infusion, compared to 32.8% without pretreatment. The marrow concentration clearance curve for the radioimmunoconjugate revealed an initial short half-life (4.75 h), suggesting rapid internalization, digestion, and release of free iodine (dehalogenation). This view was supported by a corresponding rise in trichloroacetic acid-non-precipitable activity during this period. Methods aimed at decreasing dehalogenation may result in longer residence time of the radionuclide within the marrow space, resulting in more effective tumor cell kill. This approach may provide a way to improve upon the current results obtained with marrow transplantation as treatment for patients with leukemia and other hematologic malignancies.


Assuntos
Anticorpos Monoclonais/farmacocinética , Medula Óssea/imunologia , Animais , Anticorpos Monoclonais/imunologia , Células da Medula Óssea , Cães , Granulócitos/imunologia , Fígado/metabolismo , Pulmão/metabolismo , Taxa de Depuração Metabólica , Distribuição Tecidual
9.
Transplantation ; 39(1): 9-12, 1985 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3871261

RESUMO

Female Lewis rats mated with DA male rats were given 25 or 10 mg/kg/day cyclosporine (CsA) from the time of mating to 20 days postcoitus when autopsies were performed. At the higher dose, characteristic drug-induced pathological changes in the mother were accompanied by a striking fetotoxic effect, resulting in a high incidence of fetal mortality or in runting. In addition, fetal kidneys that could be examined showed evidence of CsA-induced proximal tubular cell damage. These abnormalities were not found at the lower dosage of CsA. The fetotoxicity observed at 25 mg/kg did not appear to be dependent on major histocompatibility differences between parental strains, since it was also observed, at the same dosage, in syngeneically mated female Lewis rats.


Assuntos
Ciclosporinas/toxicidade , Feto/efeitos dos fármacos , Prenhez/efeitos dos fármacos , Animais , Bilirrubina/sangue , Relação Dose-Resposta a Droga , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Feminino , Túbulos Renais Proximais/patologia , Troca Materno-Fetal/efeitos dos fármacos , Necrose , Gravidez , Ratos , Ratos Endogâmicos Lew
10.
J Nucl Med ; 31(8): 1384-9, 1990 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2384808

RESUMO

Despite the use of near maximal doses of chemoradiotherapy, tumor recurrence remains the most frequent cause of treatment failure following marrow transplantation for leukemia. We have previously demonstrated that it is possible to selectively deliver radiation to the marrow space. In that study an initial short half-life of the radionuclide was observed. In this study we attempted to prolong the retention of the radioiodine in marrow through the use of propylthiouracil (PTU). When administered to normal dogs, PTU pretreatment resulted in improved marrow localization of 131I-labeled DM-5. There was no appreciable loss of activity from the marrow during the 2-4 hr postinjection time interval; a finding in contrast to the control animals where marrow activity declined a mean 45 +/- 0.5% over the same time period. Additionally, in contrast to controls, a rise in plasma trichloroacetic acid (TCA) nonprecipitable activity was not demonstrated in the PTU treated group during this 2-4 hr period. These results suggest that PTU's inhibition of deiodinases resulted in longer residence time of the radionuclide in its target tissue without adversely affecting distribution to non-target organs.


Assuntos
Anticorpos Monoclonais , Medula Óssea/diagnóstico por imagem , Radioisótopos do Iodo , Propiltiouracila/farmacologia , Animais , Anticorpos Monoclonais/farmacocinética , Medula Óssea/imunologia , Medula Óssea/metabolismo , Fenômenos Químicos , Química , Cães , Radioisótopos do Iodo/farmacocinética , Doses de Radiação , Cintilografia , Distribuição Tecidual
11.
Thromb Haemost ; 75(1): 127-33, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8713791

RESUMO

The proteins of fibrinolysis have been quantified in human thrombi, to assess the balance between plasminogen activators and their major inhibitor PAI-1. The relative roles of PAI-1 and alpha 2-AP were also examined since we have previously shown that both platelet PAI-1 and plasma alpha 2-AP are important determinants of clot lysis in vitro. Extracts and sections were prepared from human thrombi for quantitative immunoassay and immunohistochemical staining respectively. PAI-1 and alpha 2-AP were present at high concentrations. Levels of t-PA and t-PA-PAI-1 complex were relatively low. Staining confirmed the presence of abundant PAI-1, associated primarily with platelet material within the thrombus and also with fibrin. Staining for alpha 2-AP was also intense and demonstrated strong association with fibrin. The alpha 2-AP concentration was similar to its high plasma concentration, whereas PAI-1 levels were up to 30 times greater than that in circulating blood, suggesting that active recruitment of platelets contributes to the high PAI-1 concentration in thrombi.


Assuntos
Proteínas Sanguíneas/metabolismo , Fibrinólise/fisiologia , Inibidor 1 de Ativador de Plasminogênio/sangue , Ativadores de Plasminogênio/sangue , Trombose/sangue , Humanos , Imuno-Histoquímica , Técnicas In Vitro
12.
Immunol Lett ; 9(2-3): 93-7, 1985.
Artigo em Inglês | MEDLINE | ID: mdl-3872840

RESUMO

Administration of cyclosporin A (CS-A; 25 mg/kg daily) to rats from the time of immunization with ovalbumin (OVA) in complete Freund's adjuvant abolished the production of anti-OVA antibodies, including IgE. Cyclophosphamide (Cy; 150 mg/kg) given 2 days before immunization also inhibited specific antibody production but at the same time induced a striking eosinophilia. Combined administration of both drugs resulted in the inhibition by CS-A of the Cy-induced eosinophilia. The results suggest that IgE synthesis and eosinophil proliferation may be under the control of separate T cell subsets. This rat model may prove useful in studies on the regulation of eosinophil production and the role of these cells in disease processes.


Assuntos
Antígenos/imunologia , Ciclofosfamida/farmacologia , Ciclosporinas/farmacologia , Eosinofilia/etiologia , Imunoglobulina E/biossíntese , Animais , Feminino , Imunidade Celular/efeitos dos fármacos , Imunização , Ovalbumina/imunologia , Ratos , Ratos Endogâmicos , Linfócitos T/imunologia
13.
Br J Pharmacol ; 121(3): 540-6, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9179398

RESUMO

1. Ro 32-3555 (3(R)-(cyclopentylmethyl)-2(R)-[(3,4,4-trimethyl-2,5-dioxo-1- imidazolidinyl)methyl]-4-oxo-4-piperidinobutyrohydroxamic acid) is a potent, competitive inhibitor of human collagenases 1, 2 and 3 (Ki values of 3.0, 4.4 and 3.4 nM, respectively). The compound is a selective inhibitor of collagenases over the related human matrix metalloproteinases stromelysin 1, and gelatinases A and B (Ki values of 527, 154 and 59 nM, respectively). 2. Ro 32-3555 inhibited interleukin-1 alpha (IL-1 alpha)-induced cartilage collagen degradation in vitro in bovine nasal cartilage explants (IC50 = 60 nM). 3. Ro 32-3555 was well absorbed in rats when administered orally. Systemic exposure was dose related, with an oral bioavailability of 26% at a dose of 25 mg kg-1. 4. Ro 32-3555 prevented granuloma-induced degradation of bovine nasal cartilage cylinders implanted subcutaneously into rats (ED50 = 10 mg kg-1, twice daily, p.o.). 5. Ro 32-3555 dosed once daily for 14 days at 50 mg kg-1, p.o., inhibited degradation of articular cartilage in a rat monoarthritis model induced by an intra-articular injection of Propionibacterium acnes. 6. Ro 32-3555 is a potential therapy for the treatment of the chronic destruction of articulating cartilage in both rheumatoid and osteoarthritis.


Assuntos
Cartilagem/efeitos dos fármacos , Imidazóis/farmacologia , Inibidores de Metaloproteinases de Matriz , Inibidores de Proteases/farmacologia , Administração Oral , Animais , Artrite Experimental/tratamento farmacológico , Cartilagem/metabolismo , Bovinos , Humanos , Imidazóis/farmacocinética , Masculino , Inibidores de Proteases/farmacocinética , Ratos , Ratos Sprague-Dawley
14.
Biochem Pharmacol ; 46(11): 2104-8, 1993 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-8267661

RESUMO

Groups of male Sprague-Dawley rats received either cyclosporin A (CsA; 25 mg/kg by gavage), low dose aspirin (ASP; 20 mg/kg by gavage), a combination of both, or the appropriate drug vehicles daily for 14 days. Renal structure and function were assessed on day 0 (pretreatment) and on days 7 and 14. Compared to pretreatment results, CsA nephrotoxicity was characterized by increased plasma urea and creatinine concentrations and by moderate to severe microcalcification (MC) at the corticomedullary junction by day 14. The development of nephrotoxicity was also associated with a 5-fold increase in urine thromboxane B2 (TxB2) excretion by day 10, while that of 6-ketoprostaglandin F1 alpha remained relatively constant. Although both ASP and saline (ASP vehicle) -cotreated animals demonstrated significantly lower plasma urea and creatinine concentrations compared to treatment with CsA alone, the severity of MC observed on day 14, was reduced only in the ASP cotreatment group. Though whole blood CsA concentrations were similar at around 2400 ng/mL in all experimental groups. In addition, although a 2-fold increase in urine TxB2 excretion was observed on days 7 and 10 following treatment with CsA/ASP, levels were significantly reduced compared to treatment with either CsA alone or CsA/saline (both P < 0.05).


Assuntos
Aspirina/farmacologia , Ciclosporina/toxicidade , Nefropatias/prevenção & controle , 6-Cetoprostaglandina F1 alfa/urina , Animais , Aspirina/administração & dosagem , Creatinina/sangue , Nefropatias/induzido quimicamente , Nefropatias/urina , Masculino , Ratos , Ratos Sprague-Dawley , Tromboxano A2/urina , Ureia/sangue
15.
Autoimmunity ; 10(2): 153-63, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1723632

RESUMO

Retinal S-antigen induced experimental autoimmune uveitis (EAU) is a severe, predominantly T-cell mediated inflammatory disease of the uveal tract and retina of the eye. Pretreatment of LEW rats with the monoclonal antibody, MAbS2.4.C5, which defines an epitope in S-antigen, has been shown to effectively inhibit the subsequent induction of EAU with S-antigen. Using synthetic peptides and cyanogen bromide fragments of S-antigen we found the binding site of MAbS2.4.C5 to be located at the carboxy terminus of the molecule corresponding to amino acid positions 375 to 380. Limited Staphylococcus aureus V8 protease digestion yielded several polypeptide fragments including one large 43 kD fragment which retained antibody binding to a variety of both polyclonal and monoclonal antibodies which identify epitopes that span the length of the S-antigen. This treatment, however, completely destroys the MAbS2.4.C5 binding site and dramatically reduces uveitopathogenicity. Limited trypsin and papain digestion, on the other hand, had little effect on pathogenicity or on MAbS2.4.C5 binding to S-antigen or its peptide fragments. These results indicate that the carboxy-terminus of S-antigen plays a predominant role in the pathogenesis of EAU.


Assuntos
Anticorpos Monoclonais/imunologia , Antígenos/imunologia , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Proteínas do Olho/imunologia , Uveíte/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/uso terapêutico , Antígenos/química , Antígenos/efeitos dos fármacos , Arrestina , Autoantígenos/química , Doenças Autoimunes/prevenção & controle , Sítios de Ligação de Anticorpos , Endopeptidases/farmacologia , Epitopos/imunologia , Proteínas do Olho/química , Proteínas do Olho/efeitos dos fármacos , Feminino , Dados de Sequência Molecular , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/imunologia , Ratos , Ratos Endogâmicos Lew/imunologia , Relação Estrutura-Atividade , Uveíte/prevenção & controle
16.
J Heart Lung Transplant ; 14(4): 666-70, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7578173

RESUMO

BACKGROUND: Noninvasive studies to detect or predict acute allograft rejection after heart transplantation have failed to be sufficiently reliable to substitute for endomyocardial biopsy. Isoforms of creatine kinase MB isoenzyme (MB2 and MB1) are extremely sensitive markers of ischemic myocardial damage and, in theory, may be elevated in cardiac allograft rejection when myocardial necrosis is visible on microscopy (International Society for Heart and Lung Transplantation grade 2 or greater). METHODS: We examined, prospectively, the endomyocardial biopsy specimens (n = 256) of 50 consecutive patients undergoing orthotopic heart transplantation. Blood samples for creatine kinase MB isoforms (n = 527) were taken immediately before endomyocardial biopsy and at intervals between biopsies. RESULTS: The median ratio of MB2/MB1 in plasma samples taken at the time of biopsy for grades 2 and 3 was not significantly different from the ratio from biopsy specimens graded 0 and 1 (1.65 versus 1.33; p = Not significant). The sensitivity for diagnosing a moderately severe rejection was 47% with a specificity of 58%. However, in patients with significant acute rejection (grades 2 and 3) in whom consecutive samples were collected, the MB2/MB1 ratio was significantly increased before histologic changes seen on biopsy in 13 of 16 rejection episodes by a mean of 14 days. The sensitivity for predicting rejection (grade 2 or 3) before endomyocardial biopsy was 60% with a specificity of 71% (positive predictive value 43%, negative predictive value 86%). CONCLUSIONS: Creatine kinase MB isoforms may predict the occurrence of acute rejection before histologic evidence seen on endomyocardial biopsy.


Assuntos
Creatina Quinase/sangue , Rejeição de Enxerto/diagnóstico , Transplante de Coração/imunologia , Adolescente , Adulto , Biópsia , Cardiomiopatias/diagnóstico , Cardiomiopatias/enzimologia , Cardiomiopatias/patologia , Endocárdio/patologia , Feminino , Seguimentos , Rejeição de Enxerto/enzimologia , Rejeição de Enxerto/patologia , Transplante de Coração/patologia , Humanos , Imunossupressores/uso terapêutico , Isoenzimas , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/enzimologia , Isquemia Miocárdica/patologia , Miocárdio/patologia , Valor Preditivo dos Testes , Estudos Prospectivos
17.
Eur J Pharmacol ; 65(1): 89-92, 1980 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-7398780

RESUMO

The nature and specificity of the effect of histamine H1- and H2-receptor antagonists on the uptake of serotonin (5HT), norepinephrine (NE) and dopamine (DA) were studied in rat forebrain synaptosomes. Low concentrations (0.05-0.50 microM) of the H1-antagonist, pyrilamine, competitively inhibited 5HT uptake (Ki = 0.09 microM), had little effect on NE uptake and no effect on DA uptake. At the same concentrations, two other H1 antihistamines, promethazine and diphenhydramine, and two H2-antihistamines, metiamide and cimetidine, had no effect on 5HT or DA uptake. Diphenhydramine had a small inhibitory effect on NE uptake. It is concluded that at low concentrations, pyrilamine is a relatively selective and potent competitive inhibitor of 5HT uptake, an action which is uncharacteristic of several other antihistamines.


Assuntos
Dopamina/metabolismo , Antagonistas dos Receptores Histamínicos/farmacologia , Norepinefrina/metabolismo , Serotonina/metabolismo , Sinaptossomos/metabolismo , Animais , Cimetidina/farmacologia , Difenidramina/farmacologia , Feminino , Técnicas In Vitro , Cinética , Prometazina/farmacologia , Pirilamina/farmacologia , Ratos
18.
Eur J Pharmacol ; 51(3): 275-83, 1978 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-710503

RESUMO

Gastric ulceration produced by aspirin and indomethacin was compared in acutely stressed and non-stressed rats. We found a synergism between these anti-inflammatory agents and acute stress in the production of gastric ulcers. Even at relatively high doses, neither agent caused appreciable gastric damage in non-stressed rats, whereas moderate doses of both agents produced massive ulceration in stressed rats. The synergism appears unrelated to the effect of these agents on the pituitary-adrenal response. The size and regional distribution of ulcers produced by aspirin and indomethacin in stressed rats were comparable. However, the dose--response curves of the two drugs were markedly dissimilar. Furthermore, the ulceration produced by indomethacin was attenuated by both H1 and H2 histamine receptor antagonists, whereas ulceration produced by aspirin was attenuated only by an H2 antagonist. The results suggest that the ulcerogenic mechanism of indomethacin may differ from that of aspirin and add to the growing evidence on the importance of endogenous histamine in various forms of gastric ulceration.


Assuntos
Aspirina/farmacologia , Antagonistas dos Receptores Histamínicos/farmacologia , Indometacina/farmacologia , Úlcera Gástrica/induzido quimicamente , Animais , Aspirina/antagonistas & inibidores , Temperatura Baixa , Corticosterona/sangue , Antagonistas dos Receptores Histamínicos/uso terapêutico , Indometacina/antagonistas & inibidores , Masculino , Ratos , Restrição Física , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Estresse Fisiológico/fisiopatologia , Fatores de Tempo
19.
Brain Res Bull ; 5(3): 267-75, 1980.
Artigo em Inglês | MEDLINE | ID: mdl-7397571

RESUMO

Olivocerebellar projections were investigated in the rat using retrograde axonal transport of horseradish peroxidase. Discrete cell groups of the inferior olive were labelled, subsequent to injections in the paravermal region, the vermis, or the caudolateral hemisphere. Injections in the mid-rostrocaudal third of the paravermal area resulted in labelling of cells in the medial accessory olive (MAO), in cell group "b" at caudal levels, and in its lateral portion at mid-rostrocaudal levels. The rostral pole of the principal olive (PO), the dorsal accessory olive (DAO), and the dorsomedial cell column, were heavily labelled. By comparison, caudal paravermal injections resulted in labelling in the medial part of the mid-rostrocaudal levels of the MAO, but not in its caudal portion. The PO lamellae were labelled in their lateral half, excluding the lateral bend connecting them. Injections slightly lateral within this paravermal area gave no caudal MAO labelling, but did label cells in segments of both PO lamellae, medial to those in the previous case. From vermal injections, cell groups "b" and "c" of the caudal MAO were labelled, but no labelled cells were present in the PO. Subsequent to injections in the paramedian lobule, cells in the dorsal lamella of the PO were labelled. No cells of the MAO were labelled. These results are discussed in terms of specific labelling patterns and the general concepts of organization presently held for the olivocerebellar system.


Assuntos
Axônios/ultraestrutura , Cerebelo/anatomia & histologia , Núcleo Olivar/anatomia & histologia , Animais , Mapeamento Encefálico , Córtex Cerebelar/anatomia & histologia , Dominância Cerebral/fisiologia , Peroxidase do Rábano Silvestre , Masculino , Vias Neurais/anatomia & histologia , Neurônios/ultraestrutura , Ratos
20.
J Pers Soc Psychol ; 79(6): 1088-101, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11138756

RESUMO

The effects of community characteristics on well-being were examined among 709 African American women. Direct and moderating effects of neighborhood characteristics on distress were tested. Aggregate-level ratings of neighborhood cohesion and disorder were significantly related to distress, although the relation between cohesion and distress became nonsignificant when individual risk factors were statistically controlled. Aggregate-level neighborhood variables interacted significantly with individual risk and resource variables in the prediction of distress, consistent with trait-situation interaction theories (D. Magnusson & N. S. Endler, 1977). Community cohesion intensified the benefits of a positive life outlook. Community disorder intensified both the benefits of personal resources and the detrimental effects of personal risk factors. Results showed evidence of resilience among African American women.


Assuntos
Adaptação Psicológica , Negro ou Afro-Americano/psicologia , Identidade de Gênero , Meio Social , Identificação Social , Adulto , Criança , Feminino , Humanos , Mães/psicologia , Características de Residência , Apoio Social
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