Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 149
Filtrar
Mais filtros

Bases de dados
Tipo de documento
Intervalo de ano de publicação
1.
J Oral Pathol Med ; 44(10): 884-7, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25816896

RESUMO

BACKGROUND: Saliva contains a variety of substances and could be functionally equivalent to serum in reflecting the physiological state of the body, including metabolic variations. Salivary samples are non-invasive, safe, and easier to handle than serum. Oxidized LDL cholesterol (oxLDL) is an additional cardiovascular risk factor playing an important role in atheromatous plaque formation; overweight/obese subjects present an increase in oxLDL concentrations. The aims of the study were to assess oxLDL salivary levels, if detectable, and to verify their possible correlation with serum in overweight/obese subjects. METHODS: Thirty-five consecutive overweight/obese subjects and 10 normal weight controls were enrolled. Serum and salivary oxLDL levels were measured by a commercial enzyme-linked-immunosorbent assay (ELISA method). RESULTS: oxLDL levels were detectable in salivary samples and correlated (P = 0.001) with serum levels. Overweight/obese subjects showed serum and salivary oxLDL levels higher than controls (P = 0.000 and P = 0.022, respectively). CONCLUSIONS: Our study showed the presence of oxLDL in salivary samples and highlighted a correlation between salivary oxLDL levels and their counterpart in serum. Moreover, salivary oxLDL levels were higher in overweight/obese subjects than in controls. Therefore, a salivary sample could be functionally equivalent to serum in monitoring cardiovascular risk in overweight/obese subjects.


Assuntos
Lipoproteínas LDL/metabolismo , Obesidade/metabolismo , Sobrepeso/metabolismo , Proteínas e Peptídeos Salivares/metabolismo , Adolescente , Adulto , Idoso , Peso Corporal , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/metabolismo , Colesterol/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Lipídeos/sangue , Lipoproteínas LDL/biossíntese , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Sobrepeso/sangue , Sobrepeso/diagnóstico , Projetos Piloto , Fatores de Risco , Adulto Jovem
2.
Mar Pollut Bull ; 207: 116892, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39232412

RESUMO

The seismic water gun is widely used and plays an important role in seabed imaging acquisition; however, acoustic impacts on marine organisms are currently poorly understood. The aim of this study was to analyse the biochemical responses on the peristomial membrane (PM) of the sea urchin, Arbacia lixula, when exposed to water gun shots in open water. The PM (located around the mouth) is involved in vital functions, such as nutrition and protection. Individuals of sea urchins (n = 7 for each time slot) were sampled before, at the end, and at intervals of 3 h and 24 h after acoustic emission (duration of 20 min). Significant increases in superoxide dismutase, peroxidase, esterase and alkaline were observed immediately after water gun shots, highlighting an increase in the oxidative and inflammatory state of the tissue. Our results showed that acoustic impacts could interfere with PM vital functions, compromising the health, survival and ultimately the conservation of the species. Understanding these effects is crucial to predicting consequences on sea urchin populations and marine ecosystems.


Assuntos
Arbacia , Animais , Ouriços-do-Mar/fisiologia , Superóxido Dismutase/metabolismo
3.
Front Psychol ; 13: 817269, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36248569

RESUMO

This paper describes the Gender Equity Project (GEP) at Hunter College of the City University of New York (CUNY), funded by the U. S. NSF ADVANCE Institutional Transformation Award (ITA) program. ADVANCE supports system-level strategies to promote gender equity in the social and natural sciences, but has supported very few teaching-intensive institutions. Hunter College is a teaching-intensive institution in which research productivity among faculty is highly valued and counts toward tenure and promotion. We created the GEP to address the particular challenges that faculty, especially White women and faculty of color, face in maintaining research programs and advancing in their careers at teaching-intensive institutions. During the course of the ADVANCE award, its centerpiece was the Sponsorship Program, a multifaceted paid mentorship/sponsorship program that paired each participant with a successful scholar in her discipline. It offered extensive professional development opportunities, including interactive workshops and internal grants to support research. The GEP helped change key policies and practices by ensuring that all faculty were treated fairly in areas like provision of research start-up funds and access to guidance on how to prepare for tenure and promotion. Qualitative and quantitative evidence suggests that participation in the Sponsorship Program boosted research productivity and advanced the careers of many of the women who participated; the Program was highly rated by all participants. Some of the policy and practice changes that the GEP helped bring about were sustained at Hunter beyond the award period and some were adopted and disseminated by the central office of CUNY. However, we were not able to sustain the relatively expensive (but cost-effective) Sponsorship Program. We share the lessons we learned, including that creating a diverse, successful social and natural scientific workforce requires sustained support of female faculty employed at teaching-intensive colleges. We acknowledge the difficulties of sustaining gains, and offer ideas about how to make the case for gender equity when women seem to be doing "well enough." We underscore the imperative of building support for women's research in teaching-intensive institutions, where most women scientists are employed, and well over 90% of all college students-a disproportionate percentage of whom are female, minoritized, or both-are educated.

4.
J Exp Med ; 188(5): 855-66, 1998 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-9730887

RESUMO

Human cytomegalovirus (HCMV), a betaherpesvirus, has developed several ways to evade the immune system, notably downregulation of cell surface expression of major histocompatibility complex class I heavy chains. Here we report that HCMV has devised another means to compromise immune surveillance mechanisms. Extracellular accumulation of both constitutively produced monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor-superinduced RANTES (regulated on activation, normal T cell expressed and secreted) was downregulated in HCMV-infected fibroblasts in the absence of transcriptional repression or the expression of polyadenylated RNA for the cellular chemokine receptors CCR-1, CCR-3, and CCR-5. Competitive binding experiments demonstrated that HCMV-infected cells bind RANTES, MCP-1, macrophage inflammatory protein (MIP)-1beta, and MCP-3, but not MCP-2, to the same receptor as does MIP-1alpha, which is not expressed in uninfected cells. HCMV encodes three proteins with homology to CC chemokine receptors: US27, US28, and UL33. Cells infected with HCMV mutants deleted of US28, or both US27 and US28 genes, failed to downregulate extracellular accumulation of either RANTES or MCP-1. In contrast, cells infected with a mutant deleted of US27 continues to bind and downregulate those chemokines. Depletion of chemokines from the culture medium was at least partially due to continuous internalization of extracellular chemokine, since exogenously added, biotinylated RANTES accumulated in HCMV-infected cells. Thus, HCMV can modify the chemokine environment of infected cells through intense sequestering of CC chemokines, mediated principally by expression of the US28-encoded chemokine receptor.


Assuntos
Quimiocinas CC/metabolismo , Citomegalovirus/fisiologia , Receptores de Quimiocinas/metabolismo , Receptores Virais/metabolismo , Replicação Viral/imunologia , Sítios de Ligação , Células Cultivadas , Quimiocina CCL2/biossíntese , Quimiocina CCL2/metabolismo , Quimiocina CCL5/biossíntese , Quimiocina CCL5/metabolismo , Quimiocinas CC/genética , Meios de Cultura/metabolismo , Citomegalovirus/genética , Fibroblastos/metabolismo , Fibroblastos/virologia , Deleção de Genes , Humanos , Líquido Intracelular/metabolismo , Receptores CCR2 , Receptores de Quimiocinas/genética , Fator de Necrose Tumoral alfa/farmacologia
5.
J Am Coll Cardiol ; 10(5 Suppl B): 33B-39B, 1987 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3312371

RESUMO

In the GISSI trial, 11,712 patients with acute myocardial infarction were randomized to receive either standard care or standard care with 1.5 million units streptokinase intravenously. A highly significant reduction in mortality during hospitalization in streptokinase-treated patients was observed. The mortality at 1 year was determined in 98.3% of the patients who had been originally randomized; the 1 year mortality of patients discharged alive was similar in those patients treated with streptokinase and those who were not; that is, the beneficial effects of streptokinase treatment on survival that were observed in the hospital phase of the study persisted unchanged and with comparable statistical significance for 1 year. However, a higher incidence of reinfarction occurred in the treated versus the control groups both during the hospital phase and at the 6 month follow-up. Streptokinase treatment had no detectable effect in patients with a history of previous infarction.


Assuntos
Infarto do Miocárdio/tratamento farmacológico , Estreptoquinase/uso terapêutico , Ensaios Clínicos como Assunto , Seguimentos , Humanos , Itália , Infarto do Miocárdio/mortalidade , Prognóstico , Distribuição Aleatória , Recidiva
6.
J Am Coll Cardiol ; 23(5): 1156-61, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8144783

RESUMO

OBJECTIVES: The purpose of this study was to assess the reliability of echocardiography in the noninvasive diagnosis of acute rejection in heart transplant recipients. BACKGROUND: Although echocardiographic results seem to correlate well with allograft rejection, published data are limited and contradictory. METHODS: In 130 transplant recipients, 1,400 serial echocardiograms were recorded within 24 h of endomyocardial biopsy. Increased wall thickness, myocardial echogenicity, pericardial effusion, shorter pressure half-time, isovolumetric relaxation time and a decrease in left ventricular ejection fraction were considered markers of rejection. RESULTS: The distribution of echocardiographic markers revealed highly significant differences between bioptically graded moderate, mild and no rejection and between untreated and treated rejection episodes (both chi-square test, p < 0.0001). Specificity was 98.6% for two markers, but sensitivity was good (80%) for only moderate rejection because of the large number of false negatives in untreated patients with mild rejection. In untreated patients, there was a highly significant difference in the number of echocardiographic criteria between a benign and nonbenign outcome (chi-square test, p < 0.0001). In treated patients, the significant difference in the variation in echocardiographic criteria between favorable and unfavorable responses after 1 week was more pronounced after 2 weeks (t test, p < 0.01 vs. < 0.001). Diastolic indexes and pericardial effusion at 2 weeks seemed to be predictive of therapeutic response. CONCLUSIONS: Poor sensitivity to mild rejection indicates that serial echocardiography cannot supplant endomyocardial biopsy in the early diagnosis of acute rejection, but it seems to be a reliable noninvasive means of identifying acute rejection requiring intensified immunosuppressive therapy and of evaluating outcome.


Assuntos
Ecocardiografia , Rejeição de Enxerto/diagnóstico por imagem , Transplante de Coração , Doença Aguda , Adulto , Endocárdio/patologia , Feminino , Transplante de Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Valor Preditivo dos Testes , Sensibilidade e Especificidade
7.
J Am Coll Cardiol ; 24(3): 600-7, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8077527

RESUMO

OBJECTIVES: This analysis aimed to evaluate in a large patient cohort the relation between ST segment alterations after fibrinolytic therapy for acute myocardial infarction and 1) the combined end point of in-hospital mortality plus clinical congestive heart failure or extensive left ventricular damage, and 2) mortality 30 and 180 days after randomization. BACKGROUND: Angina relief, enzyme release acceleration and ST segment normalization are related to coronary artery reperfusion and prognosis. Electrocardiographic (ECG) evaluation before and after fibrinolytic drug administration has been used to predict short- and long-term clinical outcome in acute myocardial infarction. METHODS: Patients enrolled in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) trial underwent a standard ECG on admission and after 4 h of alteplase or streptokinase therapy; 7,426 recordings were suitable for ST segment analysis. A decrease > or = 50% in the sum of ST segment elevation in all ECG leads was adopted as the cutoff for predicting coronary artery patency. Recanalization was deemed to have occurred in 4,951 patients (group A) versus 2,475 patients without reperfusion (group B). RESULTS: Group A patients experienced a lower incidence of the combined end point than did group B patients (16.2% vs. 22.9%, respectively), as well as of all its components (death, clinical heart failure, ejection fraction < 35%, injured myocardial segment > 45%, QRS score > 10). Thirty- and 180-day mortality rates were lower in group A than group B (3.5% and 5.7% vs. 7.4% and 9.9%, respectively); relative risk (Cox) was 0.46 (95% confidence interval [CI] 0.37 to 0.57) for 30-day and 0.58 (95% CI 0.48 to 0.70) for 180-day mortality. Patients in group A had significantly less ventricular fibrillation and sustained ventricular tachycardia but more ischemic episodes (early recurrent angina plus myocardial infarction recurrence). CONCLUSIONS: A simple, inexpensive instrumental evaluation, unaffected by different epidemiologic and clinical characteristics of the population analyzed, can allow early assessment of the effectiveness of fibrinolytic treatment with respect to the main clinical outcomes.


Assuntos
Eletrocardiografia , Infarto do Miocárdio/tratamento farmacológico , Terapia Trombolítica , Idoso , Estudos de Coortes , Quimioterapia Combinada , Feminino , Seguimentos , Heparina/uso terapêutico , Humanos , Itália , Masculino , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Valor Preditivo dos Testes , Prognóstico , Estreptoquinase/uso terapêutico , Taxa de Sobrevida , Ativador de Plasminogênio Tecidual/uso terapêutico
8.
J Am Coll Cardiol ; 24(3): 608-15, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8077528

RESUMO

OBJECTIVES: This study was designed to reassess the prediction of recurrent nonfatal myocardial infarction in patients recovering from acute myocardial infarction after thrombolysis. BACKGROUND: Recurrent nonfatal myocardial infarction is a strong and independent predictor of subsequent mortality. Current knowledge of risk factors for nonfatal reinfarction is still largely based on data gathered before the advent of thrombolysis. Thus, this prospective study was planned to identify harbinger of nonfatal reinfarction in the postinfarction patients of the multicenter Grouppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) trial. METHODS: Predictors of nonfatal reinfarction at 6 months were analyzed by multivariate technique (Cox model) in 8,907 GISSI-2 survivors of myocardial infarction with clinical follow-up, relying on a set of prespecified variables reflecting residual ischemia, left ventricular failure or dysfunction, complex ventricular arrhythmias, comorbidity as well as demographic and historical factors. RESULTS: The postdischarge to 6-month incidence rate of nonfatal reinfarction was 2.5%. Independent predictors of nonfatal reinfarction were cardiac ineligibility for exercise test (relative risk 2.97, 95% confidence interval [CI] 1.98 to 4.45), previous myocardial infarction (relative risk 1.70, 95% CI 1.22 to 2.36) and angina at follow-up (relative risk 1.50, 95% CI 1.10 to 2.04). On further multivariate analysis, performed in 6,580 patients with both echocardiographic and electrocardiographic monitoring data available, a history of angina emerged as an additional risk predictor (relative risk 1.58, 95% CI 1.10 to 2.25). CONCLUSIONS: The 6-month incidence of nonfatal reinfarction is rather low in survivors of myocardial infarction after thrombolysis. Cardiac ineligibility for exercise testing and a history of coronary artery disease are risk predictors. Recurrent nonfatal infarction is not predictable by qualitative variables reflecting residual ischemia, except by postdischarge angina. Prediction of nonfatal reinfarction appears less accurate than prediction of mortality, as almost 50% of reinfarctions occur in patients without any of the identified risk factors.


Assuntos
Infarto do Miocárdio/tratamento farmacológico , Terapia Trombolítica , Análise de Variância , Angina Pectoris/etiologia , Teste de Esforço , Feminino , Seguimentos , Humanos , Sistemas de Informação , Itália , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Recidiva , Fatores de Risco , Estreptoquinase/uso terapêutico , Ativador de Plasminogênio Tecidual/uso terapêutico
9.
J Mol Biol ; 182(2): 331-40, 1985 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-3923205

RESUMO

The COOH-terminal cyanogen bromide fragment 206-316 of thermolysin has been shown to possess protein domain characteristics that are able to refold into a stable native-like structure (Fontana et al., 1982). We now report the results of limited proteolysis of this fragment with the aim of identifying the minimum size of a COOH-terminal fragment of thermolysin that is able to fold by itself. Proteolysis with subtilisin, chymotrypsin, thermolysin and trypsin allowed us to isolate to homogeneity eight different subfragments, which can be grouped in two sets of peptides, i.e. (218-222)-316 and (252-255)-316. These subfragments are able to acquire a stable conformation of native-like characteristics, as judged by quantitative analysis of secondary structure from far-ultraviolet circular dichroism spectra and immunochemical properties using rabbit anti-thermolysin antibodies. In addition, even the smallest fragment isolated (sequence 255-316) shows co-operative and reversible unfolding transitions mediated by heat (tm 65 degrees C) and guanidine hydrochloride (midpoint transition at 2.5 M denaturant), as often observed with globular proteins. From the kinetics of the proteolytic digestion and analysis of the isolated subfragments, it is concluded that proteases lead to a stepwise degradation of fragment 206-316 from its NH2-terminal region, leading to the highly helical fragment (252-255)-316, quite resistant to further proteolytic digestion. The results of this study provide evidence that it is possible to isolate stable supersecondary structures of globular proteins and correlate well with predictions of subdomains of the COOH-terminal structural domain of thermolysin.


Assuntos
Termolisina , Sequência de Aminoácidos , Aminoácidos/análise , Cromatografia em Gel , Quimotripsina , Dicroísmo Circular , Eletroforese em Gel de Poliacrilamida , Imunodifusão , Conformação Proteica , Subtilisinas , Temperatura , Termolisina/imunologia , Tripsina
10.
Curr Opin Biotechnol ; 8(4): 429-34, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9265721

RESUMO

Novel functional proteins have been generated by the transfer of active sites to structurally homologous proteins and to new structural contexts. The most successful examples of these approaches succeeded in providing effective new tools in biochemistry and protein chemistry and in suggesting new models in drug design.


Assuntos
Conformação Proteica , Engenharia de Proteínas , Proteínas Recombinantes/química , Animais , Sítios de Ligação , Desenho de Fármacos , Humanos , Modelos Estruturais , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/metabolismo , Especificidade por Substrato
11.
Mol Immunol ; 27(3): 291-5, 1990 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1692966

RESUMO

Horse and tuna cytochrome c synthetic peptides 39-53 can equally well stimulate a cytochrome c specific T cell hybridoma. The amino acid sequence of the two peptides differs mainly for the presence of a helix-breaking proline and a helix-forming glutamic acid in position 44. Circular dichroism studies of these two peptides revealed that their conformation could be drastically depending on the solvent used. These data place some limits on the correlation between structural data and biological activity.


Assuntos
Grupo dos Citocromos c/imunologia , Epitopos/imunologia , Linfócitos T/imunologia , Animais , Dicroísmo Circular , Reações Cruzadas/imunologia , Cavalos , Relação Estrutura-Atividade , Atum
12.
Mol Immunol ; 20(7): 763-8, 1983 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-6310373

RESUMO

A BALB/c cloned T cell line directed against beef apo cytochrome c was shown to exhibit the Lyt-1+2- cell surface phenotype. The fine specificity of antigen recognition exhibited by the T cell clone was assessed by using a variety of peptide preparations obtained from cytochrome c of different sources. The peptide segment recognized by this T cell clone, in conjunction with I-A region gene products, appeared similar to that bound by a monoclonal antibody specific for beef apo cytochrome c derived from the same strain of mice.


Assuntos
Especificidade de Anticorpos , Grupo dos Citocromos c/imunologia , Linfócitos T/imunologia , Sequência de Aminoácidos , Animais , Células Clonais/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C
13.
AIDS ; 12(9): 977-84, 1998 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-9662193

RESUMO

OBJECTIVE: To determine the effect of beta-chemokines on HIV-1 infection of primary macrophages, and to search for chemokine derivatives devoid of biological effects but efficient at protecting CD4+ T lymphocytes and macrophages against HIV-1. DESIGN: Use of chemically synthesized molecules devoid of biological contaminants and monocyte-derived macrophages from healthy donors. METHODS: Full-length RANTES was chemically synthesized together with three derivatives, truncated of seven, eight and nine amino acids at the amino-terminus ([8-68]RANTES, [9-68]RANTES and [10-68]RANTES), which were tested for their biological activity and antiviral effects. RESULTS: Whereas full-length and truncated RANTES derivatives bound to beta-chemokine receptor CCR-5 with the same affinity as recombinant RANTES, the truncated forms were not chemotactic and acted as CCR-5 antagonists in this respect, although a partial agonist effect was noted on cell metabolism. Full-length RANTES and [8-68]RANTES protected T lymphocytes and macrophages from infection by HIV-1, although 10-fold higher concentrations of the truncated analogues were necessary to achieve the same effect as full-length RANTES. With regard to the effect of RANTES on HIV-1 infection of primary macrophages, our results contrast with most previously reported data. CONCLUSION: These data indicate that through binding to CCR-5, truncated RANTES derivatives that are devoid of detectable biological effects may represent candidates as drugs to protect both lymphocytes and macrophages from HIV- 1.


Assuntos
Quimiocina CCL5/metabolismo , Quimiocina CCL5/farmacologia , HIV-1/fisiologia , Macrófagos/virologia , Animais , Fármacos Anti-HIV/metabolismo , Fármacos Anti-HIV/farmacologia , Células CHO , Células Cultivadas , Quimiocina CCL5/síntese química , Quimiotaxia , Cricetinae , Humanos , Leucócitos Mononucleares/fisiologia , Leucócitos Mononucleares/virologia , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Receptores CCR5/genética , Receptores CCR5/metabolismo
14.
Protein Sci ; 9(5): 942-55, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10850804

RESUMO

Helical coiled-coils and bundles are some of the most common structural motifs found in proteins. Design and synthesis of alpha-helical motifs may provide interesting scaffolds that can be useful as host structures to display functional sites, thus allowing the engineering of novel functional miniproteins. We have synthesized a 38-amino acid peptide, alpha2p8, encompassing the alpha-helical hairpin present in the structure of p8MTCP1, as an alpha-helical scaffold particularly promising for its stability and permissiveness of sequence mutations. The three-dimensional structure of this peptide has been solved using homonuclear two-dimensional NMR techniques at 600 MHz. After sequence specific assignment, a total of 285 distance and 29 dihedral restraints were collected. The solution structure of alpha2p8 is presented as a set of 30 DIANA structures, further refined by restrained molecular dynamics, using simulated annealing protocol with the AMBER force field. The RMSD values for the backbone and all heavy atoms are 0.65+/-0.25 and 1.51+/-0.21 A, respectively. Excised from its protein context, the alpha-hairpin keeps its native structure: an alpha-helical coiled-coil, similar to that found in superhelical structures, with two helices spanning residues 4-16 and 25-36, and linked by a short loop. This motif is stabilized by two interhelical disulfide bridges and several hydrophobic interactions at the helix interface, leaving most of its solvent-exposed surface available for mutation. This alpha-helical hairpin, easily amenable to synthetic chemistry and biological expression system, may represent a stable and versatile scaffold to display new functional sites and peptide libraries.


Assuntos
Dissulfetos , Biossíntese Peptídica , Peptídeos/química , Sequência de Aminoácidos , Cromatografia Líquida de Alta Pressão , Dicroísmo Circular , Simulação por Computador , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese , Biblioteca de Peptídeos , Peptídeos/síntese química , Conformação Proteica , Estrutura Secundária de Proteína , Fatores de Tempo
15.
Hypertension ; 21(4): 461-9, 1993 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8458647

RESUMO

Animal studies have shown that vasopressin secretion is modulated by arterial baroreceptors and cardiopulmonary volume receptors. Whether this is the case also in humans is controversial, however. To determine whether vasopressin is reflexly modulated by cardiac volume receptors, we studied the effect on plasma vasopressin (venous blood, radioimmunoassay) of reducing venous return and left ventricular end-diastolic diameter (echocardiography) by producing a 20-minute lower body negative pressure in 14 healthy subjects (aged 49.3 +/- 3.8 years, mean +/- SEM). The data were compared with those of 14 age-matched heart-transplant recipients, i.e., subjects with cardiac denervation. In healthy subjects, lower body negative pressure at -15 mm Hg caused a modest reduction in left ventricular end-diastolic diameter (-5 +/- 3.4%) and no change in vasopressin, whereas lower body negative pressure at -37.5 mm Hg caused a more marked reduction in left ventricular end-diastolic diameter (-12 +/- 2.5%) and a small, variable, but overall statistically significant (p < 0.05) increase in vasopressin (+145 +/- 46%, p < 0.01). The left ventricular end-diastolic diameter changes induced by the two lower body negative pressure stimuli were similar in heart-transplant recipients, but the vasopressin increase seen with the lower body negative pressure at -37.5 mm Hg was abolished. The marked increase in plasma renin activity and forearm vascular resistance induced by lower body negative pressure in healthy subjects was also abolished or drastically attenuated in heart-transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Transplante de Coração/fisiologia , Hemodinâmica , Pressorreceptores/fisiologia , Renina/sangue , Vasopressinas/sangue , Adulto , Pressão Sanguínea , Cardiomiopatias/cirurgia , Feminino , Antebraço/irrigação sanguínea , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Músculos/irrigação sanguínea , Norepinefrina/sangue , Valores de Referência , Fluxo Sanguíneo Regional , Resistência Vascular
16.
Curr Protein Pept Sci ; 1(4): 403-30, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12369907

RESUMO

Mini-proteins, polypeptides containing less than 100 amino acids, such as (animal toxins, protease inhibitors, knottins, zinc fingers, etc.) represent successful structural solutions to the need to express a specific binding activity in different biological contexts. Artificial mini-proteins have also been designed de novo, representing simplified versions of natural folds and containing natural or artificial connectivities. Both systems have been used as structural scaffolds in the engineering of novel binding activities, according to three main approaches: i) incorporation of functional protein epitopes into structurally compatible regions of mini-protein scaffolds; ii) random mutagenesis and functional selection of particular structural regions of mini-protein scaffolds; iii) minimization of protein domains by the use of sequence randomization and functional selection, combined with structural information, in an iterative process. These newly engineered mini-proteins, with specific and high binding affinities within a small size and well-defined three-dimensional structure, represent novel tools in biology, biotechnology and medical sciences. In addition, some of them can also be directly used in therapy or present high potential to serve as drugs. In all cases, they represent precious structural intermediates useful to identify frameworks for peptidomimetic design or directly lead to new small organic structures, representing novel drug candidates. The engineering of novel functional mini-proteins has the potential to become a fundamental step towards the conversion of a protein functional epitope or a flexible peptide lead into a classical pharmaceutical.


Assuntos
Peptídeos/síntese química , Engenharia de Proteínas , Estrutura Terciária de Proteína , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Sítios de Ligação , Inibidores Enzimáticos/química , Fator de Crescimento Epidérmico/química , Humanos , Imunoglobulinas/química , Dados de Sequência Molecular , Peptídeos/química , Peptídeos/metabolismo , Estrutura Secundária de Proteína
17.
FEBS Lett ; 371(2): 171-5, 1995 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-7672121

RESUMO

The single Asp53-Pro54 bond of the MTX2 toxin from the mamba snake Dendroaspis angusticeps is rapidly and efficiently cleaved in acidic solution (pH 1.5-2.5) at 45 degrees C. Unfolding of the toxin slows down the cleavage reaction by several times. Modelling studies indicate that the native toxin conformation can catalyse the Asp53-Pro54 bond cleavage. The implications of this study are: (i) cleavage of Asp-Pro bond for sequence determination may occur better in absence than in presence of denaturant, (ii) mild acid conditions, commonly used in NMR structure determinations, may irreversibly affect the structural integrity of Asp-Pro containing peptides and proteins.


Assuntos
Ácido Aspártico/metabolismo , Venenos Elapídicos/química , Venenos Elapídicos/metabolismo , Neurotoxinas/química , Neurotoxinas/metabolismo , Prolina/química , Conformação Proteica , Sequência de Aminoácidos , Cromatografia Líquida de Alta Pressão , Dicroísmo Circular , Eletroforese , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Molecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Proteínas de Répteis , Relação Estrutura-Atividade
18.
Am J Cardiol ; 72(7): 580-5, 1993 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-8362774

RESUMO

Clinical and laboratory findings were compared in 65 women and 238 men with invasively documented idiopathic dilated cardiomyopathy. Women had more severe symptoms (New York Heart Association class > or = III in 48 vs 39%; p < 0.05), presented more frequently with heart failure signs (63 vs 41%; p < 0.01), and had a higher cardiothoracic ratio (0.56 +/- 0.06 vs 0.53 +/- 0.06; p < 0.05) and higher frequency of left bundle branch block (41 vs 29%; p < 0.05). Echocardiographic measurements in women showed significantly greater left ventricular (LV) end-diastolic (42 +/- 7 vs 39 +/- 6 mm/m2; p < 0.0001) and end-systolic (36 +/- 7 vs 33 +/- 6 mm/m2; p < 0.001) diameters, and mean myocardial thickness (11 +/- 2 vs 10 +/- 2 mm; p < 0.05). Exercise duration was shorter in women than in men (7 +/- 3 vs 10 +/- 4 minutes; p < 0.001). After 18 +/- 16 months, 9 women and 27 men died, and 7 and 17, respectively, received transplants. Transplant-free survival was not significantly different according to gender. By Cox multivariate analysis, LV ejection fraction was a significant independent predictor of cardiac death or heart transplantation in both sexes (p < 0.05 in men, and p < 0.005 in women), together with left atrial diameter index (p < 0.01) in women, and mean pulmonary artery pressure (p < 0.001) in men. In conclusion, women with idiopathic dilated cardiomyopathy present a more advanced phase of the disease with greater LV dilation, but do not have a different prognosis.


Assuntos
Cardiomiopatia Dilatada/diagnóstico , Caracteres Sexuais , Adulto , Fatores Etários , Cardiomiopatia Dilatada/mortalidade , Distribuição de Qui-Quadrado , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Fatores Sexuais , Análise de Sobrevida
19.
Am J Cardiol ; 70(1): 31-3, 1992 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-1615866

RESUMO

Although thrombolytic therapy reduces mortality in patients with acute myocardial infarction (AMI), it is associated with a greater incidence of successive coronary events, and there is still no ideal diagnostic and therapeutic strategy for such patients. The present study verifies the value of negative predischarge exercise testing in identifying low-risk patients treated with thrombolysis after AMI. One hundred fifty-seven consecutive patients with an uncomplicated clinical course underwent maximal or symptom-limited exercise testing (Bruce treadmill protocol) within 15 days of AMI in the absence of therapy. The location of the AMI was anterior in 51 patients, inferior in 85 and non-Q-wave in 21. All of the patients were followed for 6 months. Death and nonfatal reinfarction were considered as major coronary events, and the recurrence of angina as a minor event. Exercise test results were negative in 105 patients (group 1) and positive for angina or ST depression greater than or equal to 0.1 mV in 52 (group 2). No deaths occurred during follow-up; there were 3 reinfarctions (3%) and 7 cases (7%) of postinfarction angina in group 1, and 2 reinfarctions (4%) and 21 cases (40%) of postinfarction angina in group 2. By the end of follow-up, 90% of the patients with negative exercise test results were event-free (97% in the case of major events). These results show that thrombolytic therapy does not affect the value of negative postinfarction exercise testing in identifying low-risk patients.


Assuntos
Teste de Esforço , Infarto do Miocárdio/tratamento farmacológico , Terapia Trombolítica , Adulto , Idoso , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Valor Preditivo dos Testes , Recidiva , Fatores de Risco
20.
Am J Cardiol ; 67(16): 1335-8, 1991 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-2042564

RESUMO

The present study compares the relative usefulness of the maximal treadmill exercise electrocardiography test with the high-dose dipyridamole echocardiography test (echocardiographic monitoring during dipyridamole infusion up to 0.84 mg/kg in 10 minutes) in detecting severe restenosis or coronary artery disease progression (greater than 70% stenosis) in asymptomatic patients 12 months after a primary successful coronary angioplasty. Criteria of positivity were: for the exercise electrocardiography test, an ST-segment shift greater than or equal to 0.1 mV from baseline, 0.08 second from the J point; for the dipyridamole echocardiography test, a transient dyssynergy of contraction, absent or of a lesser degree than that in the baseline examination. The exercise electrocardiography and dipyridamole echocardiography tests revealed a similar feasibility (91 vs 87%, difference not significant). Both tests could be performed in 75 patients. For detection of restenosis or disease progression, or both, the exercise electrocardiography test revealed a sensitivity similar to the dipyridamole echocardiography test (71 vs 71%, difference not significant), but a lower specificity (61 vs 90%). It is concluded that the high-dose dipyridamole echocardiography test is equally feasible but more accurate than the exercise electrocardiography test for noninvasive detection of severe asymptomatic restenosis or disease progression at 1 year after successful coronary angioplasty.


Assuntos
Angioplastia Coronária com Balão , Doença das Coronárias/diagnóstico , Dipiridamol , Ecocardiografia , Teste de Esforço , Angiografia Coronária , Doença das Coronárias/terapia , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Sensibilidade e Especificidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA