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1.
J Intellect Disabil ; 25(1): 131-145, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31104540

RESUMEN

BACKGROUND: Women with an intellectual disability (ID) have a similar risk of developing breast cancer as women in the general population yet present with later stage breast cancers, which have poorer outcomes. AIM: To identify whether there is a need to develop a breast cancer awareness intervention for women with an ID. METHODS: Interventions aimed at increasing cancer awareness and breast cancer awareness for people with an ID were identified and critically appraised. RESULTS: Five interventions to increase cancer awareness or breast cancer awareness in people with an ID were identified. CONCLUSION: The review highlighted the paucity of theoretically underpinned breast cancer awareness interventions specifically aimed at women with an ID. Facilitating breast cancer awareness for women with an ID could potentially lead to earlier presentation of potential symptoms of breast cancer, earlier treatment, better prognosis and ultimately, improved survival. This article establishes that there is a need for an intervention underpinned by theory to increase breast cancer awareness in women with an ID.


Asunto(s)
Neoplasias de la Mama , Discapacidad Intelectual , Neoplasias de la Mama/terapia , Femenino , Humanos , Discapacidad Intelectual/epidemiología , Discapacidad Intelectual/terapia
2.
Brachytherapy ; 15(1): 1-11, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26561277

RESUMEN

PURPOSE: To update brachytherapy recommendations for pretreatment evaluation, treatment, and dosimetric issues for thoracic brachytherapy for lung cancer. METHODS AND MATERIALS: Members of the American Brachytherapy Society with expertise in thoracic brachytherapy updated recommendations for thoracic brachytherapy based on literature review and clinical experience. RESULTS: The American Brachytherapy Society consensus guidelines recommend the use of endobronchial brachytherapy for disease palliation in patients with central obstructing lesions, particularly in patients who have previously received external beam radiotherapy. The use of interstitial implants after incomplete resection may improve outcomes and provide enhanced palliation. Early reports support the use of CT-guided intratumoral volume implants within clinical studies. The use of brachytherapy routinely after sublobar resection is not generally recommended, unless within the confines of a clinical trial or a registry. CONCLUSIONS: American Brachytherapy Society recommendations for thoracic brachytherapy are provided. Practitioners are encouraged to follow these guidelines and to develop further clinical trials to examine this treatment modality to increase the evidence base for its use.


Asunto(s)
Braquiterapia , Consenso , Neoplasias Pulmonares/radioterapia , Cuidados Paliativos , Braquiterapia/métodos , Humanos , Selección de Paciente , Radioterapia Adyuvante , Estados Unidos
3.
Arch Orthop Trauma Surg ; 136(2): 149-56, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26646845

RESUMEN

OBJECTIVE: The aim of the current study was to determine whether plate augmentation was a successful treatment algorithm for selected femoral nonunions initially managed with intramedullary nailing. MATERIALS AND METHODS: A total of 30 femoral nonunion cases were managed using the plate augmentation strategy with 13 primary cases and 17 multi-operated femurs (avg 2.8 ineffective procedures). Adjunctive strategies included autologous bone grafting and/or BMP for atrophic/oligotrophic and bone defect cases. Deformity correction was performed when required. RESULTS: Osseous union occurred in 29 of 30 cases. One multi-operated case with bone defect and prior infection required repeat autologous grafting prior to union. CONCLUSION: Plate augmentation should be added to the armamentarium for management of selected femoral nonunion that have failed initial intramedullary nailing.


Asunto(s)
Placas Óseas , Fracturas del Fémur/cirugía , Fijación Intramedular de Fracturas , Fracturas no Consolidadas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Autoinjertos , Proteínas Morfogenéticas Óseas , Femenino , Fracturas del Fémur/diagnóstico por imagen , Curación de Fractura , Fracturas no Consolidadas/diagnóstico por imagen , Humanos , Ilion/trasplante , Masculino , Persona de Mediana Edad , Radiografía , Terapia Recuperativa
4.
Arch Orthop Trauma Surg ; 135(10): 1343-7, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26188523

RESUMEN

INTRODUCTION: The aim of the current study was to determine whether application of an intramedullary hip screw for definitive management of intertrochanteric fracture was associated with post-operative deformity. Specifically this study investigated whether nail insertion would cause a "wedge effect" of the intertrochanteric fracture manifesting as lateralization of the femoral shaft and varus malalignment. MATERIALS AND METHODS: The trauma database at the University of Pittsburgh Medical Center was investigated to identify all intertrochanteric fractures (AO/OTA 31A) over the past 3 years treated with an IMHS. Fractures eligible for inclusion were performed under the supervision of a fellowship trained orthopedic trauma surgeon. All fractures were reduced in optimal alignment using percutaneous or mini-open strategies during the reaming process and nail insertion. The entry portal was over-reamed by at least 1.5 mm. Cases selected for review of the "wedge effect" had optimal post-operative imaging allowing for assessment of discrepancy between the operative and normal hip. RESULTS: Forty six patients with an average age of 77 years were included for study. Fifty percent were classified as unstable patterns. Shaft lateralization following IMHS fixation of the fractured hip was found to be an average of 7 mm greater than the contralateral intact hip (p < 0.001) (range 0-30 mm). The neck-shaft angle of the operative hips was 129° as compared to 133° on the intact side (p = 0.009). The stability of the fracture pattern was not predictive for post-operative lateralization of the femoral shaft or varus angulation (p > 0.05) (Table 2). There was no difference in post-operative deformity among techniques used for maintenance of reduction during reaming and nail insertion (p > 0.05). Despite deformity, all cases demonstrated radiographic radiographic fracture union. CONCLUSION: Despite attention to detail, the application of an intramedullary hip screw for intertrochanteric fracture has the tendency to lateralize the shaft relative to the head/neck segment (The "wedge effect").


Asunto(s)
Tornillos Óseos , Fémur/cirugía , Fijación Intramedular de Fracturas/métodos , Fracturas de Cadera/cirugía , Anciano , Clavos Ortopédicos , Femenino , Humanos , Masculino , Resultado del Tratamiento
5.
Meat Sci ; 100: 97-109, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25460112

RESUMEN

In this study, important eating quality attributes that influence consumer liking for grilled lamb loin have been identified using preference mapping techniques. The eating quality attributes identified as driving the consumer liking of lamb loin steaks were "tenderness", "sweet flavour", "meaty aftertaste", "roast lamb flavour" and "roast lamb aftertaste". In contrast, the texture attribute "rubbery" and the flavour attributes "bitter flavour" and "bitter aftertaste" had a negative influence on consumer perceptions. Associations were observed between eating quality and a number of instrumental and chemical measurements. Warner Bratzler Shear Force showed an association with "rubbery" texture and a negative association with "tenderness" and consumer liking scores. The compounds, glucose, glucose-6-phosphate, inosine, inosine monophosphate and adenosine monophosphate were associated with the attributes, "sweet flavour","meaty aftertaste", "roast lamb flavour", "roast lamb aftertaste" and with consumer scores for liking of lamb which is probably caused by the role some of these compounds play as precursors of flavour and as taste compounds.


Asunto(s)
Comportamiento del Consumidor , Glucosa-6-Fosfato/análisis , Glucosa/análisis , Carne/análisis , Purinas/análisis , Estrés Mecánico , Gusto , Adenosina Monofosfato/análisis , Animales , Culinaria/métodos , Humanos , Inosina/análisis , Inosina Monofosfato/análisis , Músculo Esquelético , Percepción , Ovinos
6.
Biotechnol Adv ; 32(4): 666-78, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-23948249

RESUMEN

Although the incidence of cancer and cancer related deaths in the United States has decreased over the past two decades due to improvements in early detection and treatment, cancer still is responsible for a quarter of the deaths in this country. There is much room for improvement on the standard treatments currently available and the National Cancer Institute (NCI) has recognized the potential for nanotechnology and nanomaterials in this area. The NCI Alliance for Nanotechnology in Cancer was formed in 2004 to support multidisciplinary researchers in the application of nanotechnology to cancer diagnosis and treatment. The researchers in the Alliance have been productive in generating innovative solutions to some of the central issues of cancer treatment including how to detect tumors earlier, how to target cancer cells specifically, and how to improve the therapeutic index of existing chemotherapies and radiotherapy treatments. Highly creative ideas are being pursued where novelty in nanomaterial development enables new modalities of detection or therapy. This review highlights some of the innovative materials approaches being pursued by researchers funded by the NCI Alliance. Their discoveries to improve the functionality of nanoparticles for medical applications includes the generation of new platforms, improvements in the manufacturing of nanoparticles and determining the underlying reasons for the movement of nanoparticles in the blood.


Asunto(s)
Nanotecnología/métodos , Neoplasias/terapia , Animales , Biomarcadores , Quimioterapia/métodos , Oro/química , Humanos , Liposomas/química , Nanopartículas del Metal/química , Nanopartículas/química , National Cancer Institute (U.S.) , Conformación de Ácido Nucleico , ARN/química , Radioterapia/métodos , Estados Unidos
7.
Eur J Cancer Care (Engl) ; 21(4): 493-504, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22329827

RESUMEN

Head and neck cancer patients are at high risk of malnutrition and its complications and therefore often undergo non-oral nasogastric or percutaneous endoscopic gastrostomy (PEG) nutrition support. However, there is little evidence that either approach is effective in this group. While one possible explanation for these findings relates to the relationship between artificial tube feeding and poor quality of life, there is little research that examines the patient's subjective experience of nutrition support. This study investigated the experiences of PEG tube feeding in head and neck cancer patients undergoing radical treatment. Conventional Q-methodology was used with 15 head and neck cancer patients, who rank-ordered 36 statements according to the extent to which these reflected their experiences of PEG tube feeding. The sorted statements were factor-analysed case-wise to provide clusters of similar experiences. Three perspectives emerged. Factor 1, labelled 'Constructive cognitive appraisal', focused around positive adaptation to, and acceptance of, PEG feeding. Factor 2, labelled 'Cognitive-affective dissonance', reflected ambivalence between cognitive acceptance and affective rejection of the PEG tube. Factor 3, labelled 'Emotion-focused appraisal', was characterised by tube-focused anxiety and fear. The findings broadly confirm Levanthal et al.'s Self-Regulatory Model of coping and support the need for genuine and individualised patient-centred nutritional care.


Asunto(s)
Nutrición Enteral/métodos , Gastrostomía , Neoplasias de Cabeza y Cuello/terapia , Satisfacción del Paciente , Adulto , Anciano , Análisis Factorial , Femenino , Neoplasias de Cabeza y Cuello/psicología , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida
8.
J Vet Pharmacol Ther ; 33(1): 1-8, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20444018

RESUMEN

The impact of nonsteroidal anti-inflammatory drugs (NSAID) on prostaglandin E(2) (PGE(2)) production and cyclooxygenase 2 (COX-2) mRNA expression in bovine whole blood (WB) cultures stimulated by lipopolysaccharide (LPS) was determined, using the blood from six Holstein dairy cattle in various stages of lactation. Peak production of PGE(2) occurred 24 h after LPS stimulation but did not result in detectable concentrations of thromboxane B(2) (TXB(2)). The NSAID indomethacin, aspirin, flunixin meglumine, and 4-[5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzene sulfonamide (PTPBS; celecoxib analogue), along with dexamethasone, were all equally effective in reducing the concentration of PGE(2) in the bovine WB culture supernatants. Bradykinin exhibited peak supernatant concentrations 1 h after LPS stimulation. Dexamethasone and the NSAID used in this study were equally effective at inhibiting bradykinin production. Peak induction of COX-2 mRNA occurred 3 h post-LPS stimulation. However, neither dexamethasone nor any of the NSAID used in this study altered COX-2 mRNA concentrations. In contrast, aspirin, flunixin meglumine, and PTPBS reduced tumor necrosis factor-alpha (TNFalpha) mRNA concentration. These results demonstrate that bovine blood cells respond to NSAID therapy like other mammalian cells with respect to inhibition of PGE(2) production and suppression of TNF mRNA induction, but do not inhibit induction of COX-2 mRNA.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Bovinos/sangre , Dinoprostona/sangre , Dinoprostona/metabolismo , Inflamación/sangre , Animales , Biomarcadores , Ciclooxigenasa 2/metabolismo , Femenino , Regulación Enzimológica de la Expresión Génica , ARN Mensajero/genética , ARN Mensajero/metabolismo
13.
Respir Med ; 96(4): 259-61, 2002 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12000005

RESUMEN

The combination of cytological and histological techniques has significantly increased the accuracy of fibreoptic bronchoscopy (FOB) in the diagnosis of lung cancer. We tested the hypothesis that cytological examination of material obtained from the whole endobronchial brush might increase the diagnostic yield in patients where conventional brush specimens were negative. Fifty patients who had undergone FOB for suspected lung cancer were studied prospectively. Bronchial lavage, bronchial biopsy and conventional brushing were performed. The whole endobronchial brush was then cut off the end of its wire and transported in a universal pot containing Shandon cytospin collection fluid. The material was dislodged from the whole brush using a vortex and the remaining fluid was centrifuged at 2,000 r.p.m. The fluid concentrate was used to maketwo cytopsin preparations. Papanicolaou stain was used. Fifty patients were studied, of which thirty-nine (78%) had endoscopicaly visible tumour. Of those, bronchial biopsy conventional brushing lavage and whole brush were positive for malignant cells in 31 (79.4%), 29 (74.3%), 21 (53.8%), and 16 (41%) of cases, respectively. A diagnosis of lung cancer was confirmed in 35 (89.7%) cases of endoscopicaly visible tumour. Conventional brushing was positive in two out of 11 (18.2%) cases with no visible tumour. Whole brush analysis was not positive in any of the cases with negative conventional brushings and was the least sensitive test in detecting malignancy Whole endobronchial brush analysis has no advantage in bronchoscopic diagnosis of patients with suspected lung cancer.


Asunto(s)
Neoplasias Pulmonares/patología , Pulmón/patología , Biopsia , Líquido del Lavado Bronquioalveolar/citología , Broncoscopía , Tecnología de Fibra Óptica , Humanos , Valor Predictivo de las Pruebas , Estudios Prospectivos
14.
Int J Radiat Oncol Biol Phys ; 51(5): 1431-6, 2001 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-11728704

RESUMEN

PURPOSE: A practical method to achieve prostate immobilization and daily target localization for external beam radiation treatment is described. METHODS AND MATERIALS: Ten patients who underwent prostate brachytherapy using permanent radioactive source placement were selected for study. To quantify prostate motion both with and without the presence of a specially designed inflatable intrarectal balloon, the computerized tomography-based coordinates of all intraprostatic radioactive sources were compared over 3 consecutive measurements at 1-min intervals. RESULTS: The placement and inflation of the intrarectal balloon were well tolerated by all patients. The mean (range) displacement of the prostate gland when the intrarectal balloon was present vs. absent was 1.3 (0-2.2) mm vs. 1.8 (0-9.1) mm (p = 0.03) at 2 min respectively. The maximum displacement in any direction (anterior-posterior, superior-inferior, or right-left) when the intrarectal balloon was inflated vs. absent was reduced to < or =1 mm from 4 mm. CONCLUSIONS: Both prostate gland immobilization and target verification are possible using a specially designed inflatable intrarectal balloon. Using this device, the posterior margin necessary on the lateral fields to ensure dosimetric coverage of the entire prostate gland could be safely reduced to 5 mm and treatment could be set up and verified using a lateral portal image.


Asunto(s)
Braquiterapia , Neoplasias de la Próstata/radioterapia , Humanos , Inmovilización , Masculino , Dosificación Radioterapéutica
15.
Health Educ Res ; 16(5): 555-66, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11675803

RESUMEN

Health messages can be generic, targeted to population subsets or tailored for individual recipients. There has been little examination of which populations need tailored interventions or whether tailored and targeted interventions differ in important ways. We used data from a mammography intervention study in two distinct populations to simulate a comparison of individually tailored versus targeted interventions. Tailored intervention content was based on individual recipients' interview responses. Targeted intervention content was based on composite group responses. For more than 60% in each population group, about two-thirds of tailored message content was a good match with content of the targeted intervention generated by composite group responses; roughly one-third of the content was 'not a good' fit for their intervention needs. Tailored interventions for more than 80% of subjects in each population differed in at least some way from those generated for all other population group members. This simulation is a first step in quantifying the contribution of individual tailoring over group targeting. Future research should examine whether a targeted intervention that is mostly a 'good' match results in behavioral outcomes similar to those of individually tailored interventions and whether particular differences in tailored versus targeted interventions yield significantly more favorable intervention outcomes.


Asunto(s)
Promoción de la Salud/métodos , Mamografía/psicología , Comunicación Persuasiva , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Investigación sobre Servicios de Salud , Humanos , Indiana , Mamografía/estadística & datos numéricos , Tamizaje Masivo , Persona de Mediana Edad , Missouri , Evaluación de Resultado en la Atención de Salud
16.
Pathology ; 33(2): 204-5, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-11358054

RESUMEN

A comparison between three nucleic acid amplification methods (COBAS AMPLICOR NG, Abbott LCx NG and in-house cppB gene PCR) for the detection of Neisseria gonorrhoeae was undertaken using non-consecutive urine specimens collected from a high prevalence asymptomatic population (260 patients) from multiple sites in Queensland, Australia. Sensitivity, specificity, positive predictive value and negative predictive value were as follows: COBAS 97.9, 93.9, 78.0, 99.5%; LCx 95.7, 100, 100, 99.1%; cppB 97.9, 100, 100, 99.5%. The results provide further evidence that false-positive COBAS AMPLICOR NG PCR results are a significant problem in our population, and that the Abbott NG LCx is a suitable alternative for screening asymptomatic populations with a high prevalence of N. gonorrhoeae carriage.


Asunto(s)
Gonorrea/orina , Neisseria gonorrhoeae/aislamiento & purificación , ADN Bacteriano/análisis , Reacciones Falso Positivas , Gonorrea/epidemiología , Humanos , Tamizaje Masivo , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Queensland/epidemiología , Sensibilidad y Especificidad
17.
Arch Pathol Lab Med ; 125(6): 799-802, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11371235

RESUMEN

Atypical fibroxanthoma can mimic other tumors, particularly spindle cell squamous cell carcinoma and spindle cell or desmoplastic melanoma. We describe a patient with chronic lymphocytic leukemia who developed acantholytic squamous cell carcinoma on the face, which recurred and metastasized to a cervical lymph node. This tumor was at first diagnosed as atypical fibroxanthoma because of its histologic and immunostaining similarity. It showed weak or negative keratin cocktail staining and strong vimentin staining. However, a recurrent tumor was immunostained for high-molecular-weight keratin and showed strong positivity. Aggressive behavior of this squamous cell carcinoma may be due to altered immune response secondary to chronic lymphocytic leukemia.


Asunto(s)
Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Histiocitoma Fibroso Benigno/diagnóstico , Histiocitoma Fibroso Benigno/metabolismo , Queratinas/metabolismo , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/metabolismo , Anciano , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/secundario , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Leucemia Linfocítica Crónica de Células B , Metástasis Linfática , Masculino , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Primarias Múltiples/metabolismo , Neoplasias Primarias Múltiples/patología , Neoplasias Cutáneas/patología , Vimentina/metabolismo
18.
Vet Immunol Immunopathol ; 79(1-2): 41-52, 2001 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-11356249

RESUMEN

The kinetics of interleukin-2 (IL-2), IL-6, IL-8 and IL-10 gene expression in concanavalin A (Con A)-activated whole blood (WB) and peripheral blood mononuclear cell (PBMC) cultures were examined using reverse transcriptase-polymerase chain reaction (RT-PCR). Unstimulated PBMC or WB cultures failed to show increases in basal cytokine PCR amplicon levels for any cytokine examined. PBMC cultures demonstrated peak expression of IL-2, IL-6, IL-8 and IL-10 mRNA levels at 12, 24, 24 and 6h, respectively. WB cultures exhibited peak IL-2, IL-6, IL-8 and IL-10 mRNA levels at 24, 12, 6 and 24h, respectively. PBMC cultures consistently exhibited higher levels of IL-2 mRNA at all times examined than did WB cultures. WB cultures consistently had higher levels of IL-6 mRNA than PBMC cultures. IL-8 and IL-10 protein levels in PBMC cultures were first detected 12h after stimulation and continued to increase in concentration through 48h. In WB cultures, IL-8 and IL-10 protein levels were first noted at 12 and 6h, respectively. WB culture IL-8 and IL-10 levels quickly reached equilibrium after being detected and remained at levels lower than those noted in PBMC cultures. These results show WB cultures represent an approach with reduced cost and time when compared to traditional cell culture and isolation methods. It may also produce an in vitro test system that more closely resembles in vivo conditions.


Asunto(s)
Citocinas/sangre , Monocitos/metabolismo , ARN Mensajero/biosíntesis , Porcinos/sangre , Animales , Citocinas/genética , Ensayo de Inmunoadsorción Enzimática/veterinaria , Interleucina-10/sangre , Interleucina-10/genética , Interleucina-2/sangre , Interleucina-2/genética , Interleucina-6/sangre , Interleucina-6/genética , Interleucina-8/sangre , Interleucina-8/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria
19.
Semin Hematol ; 38(1 Suppl 1): 37-56, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11206960

RESUMEN

Because optimal management of iron chelation therapy in patients with sickle cell disease and transfusional iron overload requires accurate determination of the magnitude of iron excess, a variety of techniques for evaluating iron overload are under development, including measurement of serum ferritin iron levels, x-ray fluorescence of iron, magnetic resonance imaging, computed tomography, and measurement of magnetic susceptibility. The most promising methods for noninvasive assessment of body iron stores in patients with sickle cell anemia and transfusional iron overload are based on measurement of hepatic magnetic susceptibility, either using superconducting quantum interference device (SQUID) susceptometry or, potentially, magnetic resonance susceptometry.


Asunto(s)
Anemia de Células Falciformes/sangre , Sobrecarga de Hierro/diagnóstico , Reacción a la Transfusión , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/terapia , Pruebas de Química Clínica , Diagnóstico por Imagen , Humanos , Sobrecarga de Hierro/etiología , Imagen por Resonancia Magnética , Magnetismo , Modelos Biológicos
20.
J Biochem ; 128(4): 705-10, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11011154

RESUMEN

Fibrinogen interactions with vascular endothelial cells are implicated in various physiological and pathophysiological events, including angiogenesis and wound healing. We have shown previously that integrin alpha(5)beta(1) is a fibrinogen receptor on endothelial cells [Suehiro, K., Gailit, J., and Plow, E.F. (1997) J. Biol. Chem. 272, 5360-5366]. In the present study, we have characterized fibrinogen interactions with purified alpha(5)beta(1) and have identified the recognition sequence in fibrinogen for alpha(5)beta(1). The binding of fibrinogen to immobilized alpha(5)beta(1) was selectively supported by Mn(2+). Fibrinogen bound to purified alpha(5)beta(1) in a time-dependent, specific, and saturable manner in the presence of Mn(2+), and the binding was blocked completely by Arg-Gly-Asp (RGD)-containing peptides and by anti-alpha(5) and anti-alpha(5)beta(1) monoclonal antibodies. A monoclonal antibody directed to the C-terminal RGD sequence at Aalpha572-574 significantly inhibited the binding of fibrinogen to alpha(5)beta(1), whereas monoclonal antibodies directed to either the N-terminal RGD sequence at Aalpha95-97 or the C-terminus of the gamma-chain did not. Furthermore, substituting RGE for RGD at position Aalpha95-97 in recombinant fibrinogen had a minimal effect on binding, whereas substituting RGE for RGD at position Aalpha572-574 decreased binding by 90%. These results demonstrate that the C-terminal RGD sequence at Aalpha572-574 is required for the interaction of fibrinogen with alpha(5)beta(1).


Asunto(s)
Fibrinógeno/química , Fibrinógeno/metabolismo , Oligopéptidos/metabolismo , Receptores de Fibronectina/metabolismo , Secuencia de Aminoácidos , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Unión Competitiva , Cationes Bivalentes/metabolismo , Cationes Bivalentes/farmacología , Fibrinógeno/genética , Fibrinógeno/inmunología , Humanos , Manganeso/metabolismo , Manganeso/farmacología , Datos de Secuencia Molecular , Mutación , Oligopéptidos/genética , Oligopéptidos/inmunología , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/inmunología , Fragmentos de Péptidos/metabolismo , Unión Proteica/efectos de los fármacos , Proteínas Recombinantes/metabolismo , Especificidad por Sustrato , Temperatura
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