RESUMEN
Heart failure (HF) is a multifactorial disorder in which clinical, environmental and genetic components take part. For this reason it is possible that common gene variants could affect development, progression and response to pharmacological therapy. In recent years the role of AGEs in the pathogenesis of cardiovascular diseases has become recognized but little is known about the role of the AGERAGE system in heart failure. The aim of the present study was to identify possible relationship between -374 T/A RAGE gene polymorphism with heart failure. The population in this study consists of 386 subjects with HF, selected according to the presence of depressed Left Ventricular Ejection Fraction (LVEF) less than45 percent, and 639 patients with CAD documented at coronary angiography. Within the population with HF there are 228 patients with disease secondary to not ischemic cause and 158 with post-ischemic condition. The sample of AA genotype was significantly lower in patients with post-ischemic HF in respect to HF secondary to non-ischemic causes (pless than0.001). A significant difference between the two groups was also observed regarding the allele frequency. In addition, differences in the allelic and the genotypic frequencies of homozygous genotypes were found between the HF patients free from evidence of coronary significant lesions and patients with at least one hemodynamically significant coronary lesion, both HF and CAD. In patients with at least one vessel compromised the presence of A allele and the homozygous AA genotype were significantly lower than in patients with lesion-free coronary. In conclusion, our research reveals that the -374 T/A polymorphism is related to the genesis of atherosclerotic coronary artery disease but not to its evolution. The protective role of AA genotype in respect to atheromatous disease is therefore confirmed also in the HF population with non-ischemic origin.
Asunto(s)
Enfermedad de la Arteria Coronaria/genética , Insuficiencia Cardíaca/genética , Receptores Inmunológicos/genética , Anciano , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Receptor para Productos Finales de Glicación AvanzadaRESUMEN
Alemtuzumab is a monoclonal antibody targeting CD52, used as induction therapy after lung transplantation (LTx). Its engagement produces a long-lasting immunodepletion; however, the mechanisms driving cell reconstitution are poorly defined. We hypothesized that miRNAs are involved in this process. The expression of a set of miRNAs, cytokines and co-signaling molecules was measured with RT-qPCR and flow cytometry in prospectively collected serum samples of LTx recipients, after alemtuzumab or no induction therapy. Twenty-six LTx recipients who received alemtuzumab and twenty-seven matched LTx recipients without induction therapy were included in the analysis. One year after transplantation four miRNAs were differentially regulated: miR-23b (p = 0.05) miR-146 (p = 0.04), miR-155 (p < 0.001) and miR-486 (p < 0.001). Expression of 3 miRNAs changed within the alemtuzumab group: miR-146 (p < 0.001), miR-155 (p < 0.001) and miR-31 (p < 0.001). Levels of IL-13, IL-4, IFN-γ, BAFF, IL-5, IL-9, IL-17F, IL-17A and IL-22 were different one year after transplantation compared to baseline. In no-induction group, concentration of sCD27, sB7.2 and sPD-L1 increased overtime. Expression of miR-23b, miR-146, miR-486, miR-155 and miR-31 was different in LTx recipients who received alemtuzumab compared to recipients without induction therapy. The observed cytokine pattern suggested proliferation of specific B cell subsets in alemtuzumab group and co-stimulation of T-cells in no-induction group.
Asunto(s)
MicroARN Circulante , Trasplante de Pulmón , MicroARNs , Alemtuzumab/uso terapéutico , Citocinas/metabolismo , Quimioterapia de Inducción , MicroARNs/genéticaRESUMEN
Inflammation plays a key role in atherosclerosis. Galectin-3 is a macrophage- and endothelium-derived mediator actively involved in the regulation of many aspects of inflammatory cell behaviour. The aim of this study is to quantify plasma Galectin-3 in patients with coronary artery disease (CAD) and different clinical manifestation at the moment of observation in order to verify whether Galectin-3 could be a useful biomarker of atherosclerotic state. We enrolled 125 patients affected by CAD, angiographically documented (70 stable, 55 unstable). They underwent accurate examinations and anamnestic data was collected. The most important traditional risk factors, such as age, hypertension, and body mass index, were reported. Plasma Galectin-3 was quantified using an ELISA kit. Unstable patients (n = 55) had a higher plasma Galectin-3 levels in respect to the stable subjects (27.75 ng/mL (19.27-39.09) vs 6.48 ng/ml (4.88-8.83), p<0.001. A trend in correlation between plasma Galectin-3 levels and number of vessels compromised seems to be present: CAD patients with three-vessel disease had higher levels of Galectin-3 than patients with one-or two-vessel disease (17.39 ng/ml (10.75-29.82) vs 9.18 ng/ml (5.56-23.22), p= 0.058. The significantly higher plasma Galectin-3 levels in patients with unstable angina in respect to the stable angina confirm the involvement of Galectin-3 in promoting macrophage activation and monocyte attraction. Despite the distribution of CAD in patients with acute and chronic coronary disease being similar, we may hypothesize that Galectin-3 could be a useful biomarker of atherosclerotic plaque and in particular of its destabilization.
Asunto(s)
Síndrome Coronario Agudo/sangre , Angina Inestable/sangre , Galectina 3/sangre , Infarto del Miocardio/sangre , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/inmunología , Anciano , Angina Inestable/diagnóstico por imagen , Angina Inestable/inmunología , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Angiografía Coronaria , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/inmunología , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Regulación hacia ArribaRESUMEN
The receptor for advanced glycation end product (RAGE) is thought to play an important role in inflammation. Chronic fatigue syndrome (CFS) is a long-lasting fatigue that compromises at least 50% of a subject's daily activities without other known cause. Immune dysfunction has been implicated and an association with a peculiar genetic cytokine profile, predisposing to an immunomodulatory response of inflammatory nature, was found. The aim of this study is to analyse RAGE polymorphisms and HLA-DRB1 alleles in seventy-five Italian CFS patients and 141 controls matched for age, sex and ethnicity. These two groups underwent genomic study for RAGE 374T/A and 429C/T promoter polymorphisms; moreover, 46 patients and 186 controls were typed for HLA-DRB1 at low resolution molecular level. Of these, 31 patients and 99 controls also underwent high resolution analysis to define the HLA-DRB1*11 and DRB1*13 alleles. The haplotypes RAGE-374T, DRB1*04; RAGE-374T, DRB1*09; RAGE-374T, DRB1*11; RAGE-374A, DRB1*13; RAGE-429T, DRB1*04 and RAGE-429C, DRB1*11 were significantly more frequent in CFS patients, whereas RAGE-429C, DRB1*07 would seem protective. A significantly lower frequency of DRB1*1104 (5.4% vs 12.9% p=0.04, OR=0.39) and a significantly higher frequency of HLA-DRB1*1301 (13.0% vs 5.1% p=0.006, OR= 2.79) were found in CFS patients. A synergic effect was observed with RAGE polymorphism. The OR values strengthened in the following cis combinations: RAGE-374A, HLA-DRB1*1104 (OR=0.27) and RAGE-374A, HLADRB1*1301 (OR=6.23). HLA haplotypes rather than single alleles of RAGE or of DRB1 genes seem to be involved in CFS, probably including a subregion of major interest.
Asunto(s)
Síndrome de Fatiga Crónica/genética , Antígenos HLA-DR/genética , Polimorfismo Genético , Regiones Promotoras Genéticas , Receptores Inmunológicos/genética , Estudios de Casos y Controles , Síndrome de Fatiga Crónica/epidemiología , Síndrome de Fatiga Crónica/inmunología , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Cadenas HLA-DRB1 , Haplotipos , Humanos , Italia , Desequilibrio de Ligamiento , Oportunidad Relativa , Receptor para Productos Finales de Glicación Avanzada , Medición de Riesgo , Factores de RiesgoRESUMEN
Titanium-based implants are successfully used for various biomedical applications. However, in some cases, e.g. in dental implants, failures due to bacterial colonization are reported. Surface modification is a commonly proposed strategy to prevent infections. In this work, titanium oxide, naturally occurring on the surface of titanium, was modified by promoting the formation of a mixed titanium and zinc oxide, on the basis of the idea that zinc oxide on titanium surface may act as the zinc oxide used in pharmaceutical formulation for its lenitive and antibacterial effects. The present work shows that it is possible to form a mixed titanium and zinc oxide on titanium surfaces, as shown by Scanning Electron Microscopy and XPS analysis. To this end titanium was preactivated by UV on crystalline titanium oxide, both in the anatase form or in the co-presence of anatase and rutile. By performing antibacterial assays, we provide evidence of a significant reduction in the viability of five streptococcal oral strains on titanium oxide surfaces modified with zinc. In conclusion, this type of chemical modification of titanium oxide surfaces with zinc might be considered a new way to reduce the risk of bacterial colonization, increasing the lifetime of dental system applications.
Asunto(s)
Antibacterianos/farmacología , Biopelículas/crecimiento & desarrollo , Materiales Biocompatibles Revestidos/farmacología , Streptococcus/efectos de los fármacos , Titanio/química , Zinc/química , Materiales Biocompatibles Revestidos/química , Implantes Dentales/microbiología , Microanálisis por Sonda Electrónica , Pruebas de Sensibilidad Microbiana/clasificación , Microscopía Electrónica de Rastreo , Streptococcus/clasificación , Streptococcus/genética , Propiedades de Superficie/efectos de la radiación , Titanio/efectos de la radiación , Rayos Ultravioleta , Zinc/efectos de la radiación , Óxido de Zinc/químicaRESUMEN
The binding of fibronectin and fibronectin fragments to the enterotoxigenic strain E. coli B34289c was studied. E. coli cells bound to two distinct sites of fibronectin, one being the N-terminal domain, which also contains the binding sites for staphylococci and streptococci, and the other located within the central heparin binding region. In addition, the N-terminal and the heparin binding domain mediated the attachment of bacteria in a solid phase binding assay. E. coli cells expressed two classes of receptors, the first, a 17 kDa protein, recognized by the N-terminal fragment and the second, having a mol. mass of 55 kDa, which interacts with the internal heparin binding domain. Bacterial receptors, which bind the N-terminal end of fibronectin, may be structurally related.
Asunto(s)
Adhesión Bacteriana , Enterotoxinas/biosíntesis , Escherichia coli/metabolismo , Fibronectinas/metabolismo , Sitios de Unión , Escherichia coli/patogenicidad , Fibronectinas/química , Peso Molecular , Fragmentos de Péptidos/química , Fragmentos de Péptidos/metabolismo , Mapeo Peptídico , Unión Proteica , Staphylococcus/metabolismo , Streptococcus/metabolismoAsunto(s)
Glaucoma de Ángulo Abierto/complicaciones , Desprendimiento de Retina/complicaciones , Adolescente , Adulto , Anciano , Femenino , Glaucoma/diagnóstico , Humanos , Terapia por Láser , Masculino , Persona de Mediana Edad , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/cirugía , Curvatura de la EscleróticaRESUMEN
An enterotoxigenic strain of Escherichia coli, B34289c, has been shown to bind the N-terminal region of fibronectin with high affinity (G. Fröman, L. M. Switalski, A. Faris, T. Wadström, and M. Höök, J. Biol. Chem. 259:14899-14905, 1984). We now report that this strain also binds collagen. The binding of 125I-labeled type II collagen to bacteria was time dependent and reversible. Bacteria expressed a limited number of collagen receptors (2.2 x 10(4) per cell) and bound collagen with a Kd of 20 nM. All collagen types tested (I to V) as well as all tested cyanogen bromide-generated peptides [alpha 1(I)CB2, alpha 1(I)CB3, alpha 1(I)CB7, alpha 1(I)CB8, and alpha 2(I)CB4] were recognized by bacterial receptors, as demonstrated by the ability of these proteins to inhibit the binding of 125I-labeled collagen to bacteria. Of several unlabeled proteins tested in competition experiments, fibronectin and its N-terminal region strongly inhibited binding of the radiolabeled collagen to E. coli cells. Conversely, collagen competed with an 125I-labeled 28-kilodalton fibronectin fragment for bacterial binding. Collagen bound to bacteria could be displaced by excess amounts of either unlabeled fibronectin or its N-terminal fragment. Similarly, collagen could displace 125I-labeled N-terminal peptide of fibronectin bound to the bacterial cell surface. Bacteria grown at 41 degrees C or in the presence of glucose did not express collagen or fibronectin receptors. These results indicate the presence of specific binding sites for collagen on the surface of E. coli cells and furthermore that the collagen and fibronectin binding sites are located in close proximity, possibly on the same structure.
Asunto(s)
Colágeno/metabolismo , Escherichia coli/metabolismo , Sitios de Unión , Fibronectinas/metabolismo , Radioisótopos de Yodo , Laminina/metabolismo , Receptores de Superficie Celular/análisis , Receptores de ColágenoRESUMEN
Firstly, the more distinctive features of the morphology and semeiology of the normal optic disk and peripapillary region are discussed. The authors then outline the principal morphological and functional characteristics of glaucomatous optic neuropathies. An appropriate description of the optic disorders which may resemble glaucoma follows. This section reviews separately the vascular disorders considered the most significant from the point of view of frequency and clinical scope, and non-vascular disorders of a heterogeneous nature (toxic, inflammatory, degenerative, malformative and compressive). Finally, the dangers of diagnostic confusion in such cases are mentioned and the most pertinent clinical characteristics for the differentiation between glaucomatous and glaucomatous-like forms are discussed.
Asunto(s)
Glaucoma , Enfermedades del Nervio Óptico , Glaucoma/patología , Glaucoma/fisiopatología , Humanos , Disco Óptico/patología , Disco Óptico/fisiopatología , Enfermedades del Nervio Óptico/patología , Enfermedades del Nervio Óptico/fisiopatologíaRESUMEN
The binding of fibronectin to Staphylococci exhibits the properties of a ligand-receptor interaction and has been proposed to mediate bacterial adherence to host tissues. To localize staphylococcal-binding sites in fibronectin, the protein was subjected to limited proteolysis and, of the generated fragments, Staphylococci appeared to preferentially bind to the N-terminal fragment. Different fibronectin fragments were isolated and tested for their ability to inhibit 125I-fibronectin binding to Staphylococci. The results indicate that only the N-terminal region effectively competed for fibronectin binding. However, when isolated fragments were adsorbed to microtiter wells, we found that two distinct domains, corresponding to the N-terminal fragment and to the heparin-binding peptide mapping close to the C-terminal end of fibronectin, promoted the attachment of both Staphylococcus aureus Newman and coagulase-negative strain of Staphylococcus capitis 651. These same domains were recognized by purified 125I-labeled staphylococcal receptor, either when immobilized on microtiter wells or probed after adsorption onto nitrocellulose membrane. The heparin-binding domain is comprised of type-III-homology repeats 14, 15 and 16. To determine which repeats participate in this interaction, we isolated and tested repeats type III14 and type III16. We found that the major staphylococcal binding site is located in repeat type III14. The staphylococcal receptor bound the N-terminal domain of fibronectin with a KD of 1.8 nM, whereas the dissociation constant of the receptor molecule for the internal heparin-binding domain was 10 nM. Since the fusion protein ZZ-FR, which contains the active sequences of fibronectin receptor (D1-D3) bound only to the N-terminus, it is reasonable to assume that the bacterial receptor may have additional binding sites outside the D domains, capable of interacting with the internal heparin-binding domain of fibronectin.
Asunto(s)
Fibronectinas/metabolismo , Receptores Inmunológicos/metabolismo , Staphylococcus aureus/metabolismo , Sitios de Unión , Unión Competitiva , Western Blotting , Fibronectinas/aislamiento & purificación , Heparina/metabolismo , Cinética , Fragmentos de Péptidos/aislamiento & purificación , Fragmentos de Péptidos/metabolismo , Receptores de Fibronectina , Receptores Inmunológicos/aislamiento & purificación , Proteínas Recombinantes de Fusión/aislamiento & purificación , Proteínas Recombinantes de Fusión/metabolismoRESUMEN
In this report we have analyzed the binding of collagen to Streptococcus pyogenes strain 6414. This binding was rapid, specific, and involved a limited number of receptor molecules (11,600 copies per cell). When the proteins in a streptococcal lysate were blotted onto a nitrocellulose filter and probed with 125I-labeled collagen, a prominent collagen-binding protein of 57 kDa was identified as well as minor 130-150-kDa components. The major 57-kDa protein was isolated by affinity chromatography on collagen-Sepharose followed by gel filtration chromatography. The 57-kDa protein purified from S. pyogenes was used to raise a monospecific antibody which also reacted with a collagen-binding protein of similar molecular size isolated from Streptococcus zooepidemicus. The two collagen-binding proteins from streptococci have a similar amino acid composition and isoelectric points. Isolated collagen-binding protein was specifically recognized by 125I-collagen in a solid-phase binding assay and displayed an affinity for the ligand quite similar to that exhibited by intact bacteria (Kd = 3.1 versus 3.5 x 10(-9) M, respectively). Surface-labeled bacteria attached to microtiter wells coated with different collagen types and the 57-kDa protein blocked the adhesion to collagen substrate. We propose that the 57-kDa protein is an adhesin involved in the attachment of streptococci to host tissues.
Asunto(s)
Proteínas Portadoras/aislamiento & purificación , Integrinas/aislamiento & purificación , Streptococcus pyogenes/metabolismo , Secuencia de Aminoácidos , Animales , Proteínas Portadoras/metabolismo , Bovinos , Cromatografía de Afinidad , Cromatografía en Gel , Electroforesis en Gel de Poliacrilamida , Integrinas/metabolismo , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Unión Proteica , Receptores de Colágeno , Streptococcus equi/metabolismoRESUMEN
In vitro experiments indicate that components of the host present in body fluids may prevent the attachment of human immunodeficiency virus type 1 (HIV-1) to target cells. Fibronectin (Fn), a dimeric 440-kDa extracellular matrix adhesion protein, is secreted by mesenchymal cells and assembled into insoluble matrices. Fn exerts important effects on cell growth and differentiation through a number of discrete functional domains. Several microorganisms are known to bind Fn. We show that, under physiological conditions, HIV-1 gp120 and gp160 are capable of binding plasma and cellular Fn as well as laminin and vitronectin. Experiments were set up to analyze in detail the binding of HIV gp120 and gp160 to Fn. The gp120 and gp160 specifically recognize the C-terminal heparin-binding domain of Fn (Fn-CTHBD) with a calculated KD of 2.8 x 10(-7) M for gp160. Binding of gp160 to Fn-CTHBD is a saturable and specific process that is blocked by antibodies to Fn-CTHBD and by heparin and is inhibited to a minor extent by heparan sulfate and dextran sulfate. These observations suggest that gp120/160 specifically recognize the III15 repeat within Fn-CTHBD. Intact Fn and Fn-CTHBD strongly inhibit the interaction of gp120/160 with soluble CD4 and, under low serum conditions, are capable of neutralizing the infectivity of HIV-1 for CD4-positive T cells. Thus, Fn that is present in plasma and mucinous secretions may well affect HIV infectivity and virus distribution in vivo.
Asunto(s)
Fibronectinas/metabolismo , Proteína gp120 de Envoltorio del VIH/metabolismo , Proteínas gp160 de Envoltorio del VIH/metabolismo , VIH-1/metabolismo , Anticuerpos/farmacología , Western Blotting , Antígenos CD4/metabolismo , Células Cultivadas , Relación Dosis-Respuesta a Droga , Fibrinógeno/metabolismo , Fibronectinas/química , Fibronectinas/inmunología , Fibronectinas/farmacología , VIH-1/efectos de los fármacos , VIH-1/patogenicidad , Heparina/farmacología , Humanos , Cinética , Laminina/metabolismo , Orosomucoide/metabolismo , Especificidad por Sustrato , Linfocitos T/virología , Vitronectina/metabolismo , alfa-Fetoproteínas/metabolismoRESUMEN
A monoclonal antibody 3A10, generated from a mouse immunized with the Streptococcus dysgalactiae fibronectin (Fn) binding protein FnbA, was isolated, and its effect on ligand binding by the antigen was examined. The epitope for 3A10 was localized to a previously unidentified Fn binding motif (designated An) just N-terminal of the repeat domain which represents the primary ligand binding site on FnbA. Fn binding to Au was enhanced by 3A10 rather than inhibited. This effect was demonstrated in two different assays. First, in the presence of 3A10 the Au-containing proteins and synthetic peptide more effectively competed with bacterial cells for binding to Fn. Second, 3A10 dramatically increased the binding of biotin-labeled forms of the Au-containing proteins to Fn immobilized on a blotting membrane. Pure 3A10 IgG did not recognize the antigen by itself, and Fn was required for the immunological interaction between the antibody and the epitope. This induction effect of Fn was shown in both Western blot and enzyme-linked immunosorbent assay in which immobilized Au-containing molecules were probed with 3A10 in the presence of varying concentrations of Fn. Specificity analyses of 3A10 revealed that the monoclonal also recognized a ligand binding motif in a Streptococcus pyogenes Fn binding MSCRAMM but not the corresponding motifs in two related adhesins from Staphylococcus aureus and S. dysgalactiae. Furthermore, 3A10 stimulated Fn binding by S. pyogenes cells. These results together with subsequent biophysical studies presented in the accompanying paper (House-Pomepeo, K., Xu, Y., Joh, D., Speziale, P., and Höök, M. (1996) J. Biol. Chem. 271, 1379-1384) indicate that the ligand binding sites of Fn binding MSCRAMMs have little or no secondary structure. However, on binding to Fn, they appear to undergo a structural rearrangement resulting in a defined structure rich in beta sheet and expressing a ligand-induced binding site for antibodies such as 3A10.
Asunto(s)
Adhesinas Bacterianas/inmunología , Anticuerpos Monoclonales/farmacología , Proteínas Bacterianas/inmunología , Fibronectinas/inmunología , Streptococcus/inmunología , Secuencia de Aminoácidos , Animales , Especificidad de Anticuerpos , Proteínas Bacterianas/aislamiento & purificación , Secuencia de Bases , Cartilla de ADN , Ensayo de Inmunoadsorción Enzimática , Epítopos/análisis , Fibronectinas/aislamiento & purificación , Cinética , Ratones/inmunología , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/aislamiento & purificación , Homología de Secuencia de Aminoácido , Staphylococcus aureus/inmunología , Streptococcus pyogenes/inmunologíaRESUMEN
Binding of bacteria to fibronectin has been implicated as a mechanism of bacterial adhesion to the host tissue. In this report we have analyzed the binding of a strain of Streptococcus dysgalactiae to fibronectin. The cells bind to a site in the NH2-terminal domain of the protein via trypsin-sensitive cell surface components. Furthermore, a lysate prepared by sonication of streptococcal cells contained fibronectin-binding proteins that inhibit the binding of the ligand to intact bacteria. When the proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, blotted to an Immobilon-P filter, and probed with 125I-labeled fibronectin, a 140-kDa fibronectin-binding protein was identified along with a number of smaller binding proteins. A genomic DNA library was constructed and screened for the expression of fibronectin-binding proteins. Two clones were isolated and shown to contain unrelated inserts by restriction mapping and cross-hybridization experiments. The two encoded proteins were also immunologically distinct although both bound to the same region of the fibronectin molecule, and both effectively inhibited the binding of 125I-fibronectin to bacterial cells. Immunological analyses showed that only one of the two proteins tentatively identified as fibronectin receptors was expressed in detectable quantities in the Streptococcus dysgalactiae strain under the culture conditions employed.
Asunto(s)
Receptores Inmunológicos/genética , Streptococcus/genética , Adhesión Bacteriana , Unión Competitiva , Cromatografía de Afinidad , Cromatografía por Intercambio Iónico , Cromatografía Liquida , Clonación Molecular , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , Electroforesis en Gel de Poliacrilamida , Escherichia coli/genética , Fibronectinas/metabolismo , Biblioteca Genómica , Cinética , Plásmidos , Receptores de Fibronectina , Receptores Inmunológicos/aislamiento & purificación , Receptores Inmunológicos/metabolismo , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Mapeo Restrictivo , Streptococcus/inmunologíaRESUMEN
One hundred and eight non insulin-dependent diabetics were tested for alcohol flushing after chlorpropamide administration (CPAF test). The overall prevalence of patients who flushed at the first challenge was 32%. However, nearly half of them still flushed after alcohol administration, when placebo was given instead of chlorpropamide, so that the prevalence of 'true' flushers was only 17%. Even though the distribution of retinal lesions was similar in 'true' flushers and in non flushers, severe loss of visual acuity was confined to the non flushers and aspecific flushers. The frequency of pathological ECG findings and of peripheral pulse reduction or abolition was significantly higher in the non flushers and aspecific flushers. Blood pressure, serum lipids and hemostatic parameters were similar in the two groups, and therefore do not explain the differences in prevalence of lesions. This study confirms the previous findings of a lower prevalence of large vessel lesions in flushers; however, the prevalence of 'true' CPAF phenomenon in our out-patient population appears to be much lower than previously reported.