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1.
Ann Oncol ; 22(9): 2086-2093, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21343383

RESUMEN

BACKGROUND: A pilot study (NCT00316563) to determine if delta-9-tetrahydrocannabinol (THC) can improve taste and smell (chemosensory) perception as well as appetite, caloric intake, and quality of life (QOL) for cancer patients with chemosensory alterations. PATIENTS AND METHODS: Adult advanced cancer patients, with poor appetite and chemosensory alterations, were recruited from two sites and randomized in a double-blinded manner to receive either THC (2.5 mg, Marinol(®); Solvay Pharma Inc., n = 24) or placebo oral capsules (n = 22) twice daily for 18 days. Twenty-one patients completed the trial. At baseline and posttreatment, patients completed a panel of patient-reported outcomes: Taste and Smell Survey, 3-day food record, appetite and macronutrient preference assessments, QOL questionnaire, and an interview. RESULTS: THC and placebo groups were comparable at baseline. Compared with placebo, THC-treated patients reported improved (P = 0.026) and enhanced (P < 0.001) chemosensory perception and food 'tasted better' (P = 0.04). Premeal appetite (P = 0.05) and proportion of calories consumed as protein increased compared with placebo (P = 0.008). THC-treated patients reported increased quality of sleep (P = 0.025) and relaxation (P = 0.045). QOL scores and total caloric intake were improved in both THC and placebo groups. CONCLUSIONS: THC may be useful in the palliation of chemosensory alterations and to improve food enjoyment for cancer patients.


Asunto(s)
Dronabinol/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/fisiopatología , Percepción Olfatoria/efectos de los fármacos , Cuidados Paliativos/métodos , Percepción del Gusto/efectos de los fármacos , Anciano , Método Doble Ciego , Dronabinol/efectos adversos , Femenino , Humanos , Masculino , Proyectos Piloto , Placebos , Calidad de Vida
2.
Curr Oncol ; 25(5): e480-e485, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30464700

RESUMEN

Palliative care (pc) is part of the recommended standard of care for patients with advanced cancer. Nevertheless, delivery of pc is inconsistent. Patients who could benefit from pc services are often referred late-or not at all. In planning for improvements to oncology pc practice in our health care system, we sought to identify barriers to the provision of earlier pc, as perceived by health care providers managing patients with metastatic colorectal cancer (mcrc). We used the Michie Theoretical Domains Framework (tdf) and Behaviour Change Wheel (bcw), together with knowledge of previously identified barriers, to develop a 31-question survey. The survey was distributed by e-mail to mcrc health care providers, including physicians, nurses, and allied staff. Responses were obtained from 57 providers (40% response rate). The most frequently cited barriers were opportunity-related-specifically, lack of time, of clinic space for consultations, and of access to specialist pc staff or services. Qualitative responses revealed that resource limitations varied by cancer centre location. In urban centres, time and space were key barriers. In rural areas, access to specialist pc was the main limiter. Self-perceived capability to manage pc needs was a barrier for 40% of physicians and 30% of nurses. Motivation was the greatest facilitator, with 89% of clinicians perceiving that patients benefit from pc. Based on the Michie tdf and bcw model, interventions that best address the identified barriers are enablement and environmental restructuring. Those findings are informing the development of an intervention plan to improve oncology pc practices in a publicly funded health care system.


Asunto(s)
Actitud del Personal de Salud , Neoplasias Colorrectales/terapia , Cuidados Paliativos , Médicos , Recursos en Salud , Humanos , Oncología Médica , Encuestas y Cuestionarios
3.
J Biomech ; 49(9): 1593-1600, 2016 06 14.
Artículo en Inglés | MEDLINE | ID: mdl-27062592

RESUMEN

The study of steal mechanisms caused by vessel obstructions is of the utmost importance to gain understanding about their pathophysiology, as well as to improve diagnosis and management procedures. The goal of this work is to perform a computational study to gain insight into the hemodynamic forces that drive blood flow steal mechanisms caused by subclavian artery stenosis. Such condition triggers a flow disorder known as subclavian steal. When this occurs in patients with internal thoracic artery anastomosed to the coronary vessels, the phenomenon includes a coronary-subclavian steal. True steal can exist in cases of increased arm blood flow, potentially resulting in neurological complications and, in the case of coronary-subclavian steal, graft function failure. In this context, the anatomically detailed arterial network (ADAN) model is employed to simulate subclavian steal and coronary-subclavian steal phenomena. Model results are verified by comparison with published data. It is concluded that this kind of model allows us to effectively address complex hemomdynamic phenomena occurring in clinical practice. More specifically, in the studied conditions it is observed that a regional brain steal occurs, primarily affecting the posterior circulation, not fully compensated by the anterior circulation. In the case of patients with coronary revascularization, it is concluded that there is a large variability in graft hemodynamic environments, which physically explain both the success of the procedure in cases of severe occlusive disease, and the reason for graft dysfunction in mildly stenosed left anterior descending coronary artery, due to alternating graft flow waveform signatures.


Asunto(s)
Hemodinámica , Modelos Biológicos , Síndrome del Robo de la Subclavia/fisiopatología , Encéfalo/irrigación sanguínea , Vasos Coronarios/fisiopatología , Arteria Subclavia/fisiopatología
4.
J Biomech ; 45(12): 2066-73, 2012 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-22771032

RESUMEN

The present work deals with the parameter identification problem in outflow models used in one-dimensional simulations of arterial blood flow. Specifically, the resistive elements that define the models used to account for the blood supply to the vascular territories in arterial networks are computed by solving a system of non-linear equations using a Broyden method. This strategy is employed to compute the terminal parameters in the vascular territories of an anatomically detailed model of the arm comprising 67 arterial segments and 16 vascular territories. A comparison with a simple analytical approach, in terms of vascular territory resistances, average blood flows and time-dependent hemodynamic quantities, is performed. Also, a sensitivity analysis is presented to assess the performance of this new approach in normal and abnormal cardiovascular scenarios. This identification procedure allows to correctly set up hemodynamics simulations in highly detailed arterial networks making possible to gain insight in the aspects related to the blood circulation in arterial vessels.


Asunto(s)
Arterias/fisiología , Modelos Cardiovasculares , Resistencia Vascular/fisiología , Velocidad del Flujo Sanguíneo/fisiología , Humanos
5.
Proc Natl Acad Sci U S A ; 78(5): 2864-8, 1981 May.
Artículo en Inglés | MEDLINE | ID: mdl-6942407

RESUMEN

We address the question of whether substituting 2-aminopurine (APur) in place of adenine (Ade) in DNA can increase the frequency of base mispairing with cytosine. Using DNA polymerase alpha to measure the rates of inserting deoxycytidine and thymidine nucleotides in direct competition with each other for APur or Ade sites on synthetic copolymer DNA templates, we observe that the ratio of dCMP to dTMP insertion is increased by a factor of at least 230 when APur replaces Ade on a poly(dA) template and by a factor of 35 when APur replaces Ade on a poly(dC,dA) template. These data support the idea that APur.C base mispairs are directly involved in APur induction of A.T leads to G.C transition mutations. The observed misinsertion frequency of cytosine substituting for thymine opposite template APur sites is about 5%. This value is in excellent agreement with earlier predictions and measurements for APur.C heteroduplex-heterozygote frequencies in T4 bacteriophage in vivo.


Asunto(s)
2-Aminopurina , Adenina , Citosina , ADN Nucleotidiltransferasas/metabolismo , ADN Polimerasa II/metabolismo , ADN Polimerasa Dirigida por ADN/metabolismo , ADN/genética , Mutación , Adenina/análogos & derivados , Animales , Composición de Base , Carcinoma , Bovinos , Línea Celular , Humanos , Cinética , Neoplasias de la Boca , Moldes Genéticos , Timo/enzimología
6.
J Virol ; 25(1): 73-7, 1978 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-621787

RESUMEN

Bacteriophage T4 genes 32, 41, 44, 45, 56, and 62 are essential to DNA replication. Amber mutants (suppressed by su+1, su+2, or su+3 bacteria) in these genes were examined for any mutator or antimutator effects on the reversion of a transition mutation. In every case except for mutations in gene 56, elevated or lowered error frequencies were observed. These results indicate the importance of all of the replicative proteins in the determination of error frequency.


Asunto(s)
Colifagos/genética , ADN Viral/genética , Genes Virales , Mutación , Supresión Genética , Replicación del ADN , Fenotipo
7.
Proc Natl Acad Sci U S A ; 79(21): 6429-33, 1982 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-6959128

RESUMEN

Enzyme kinetic measurements are presented showing that Km rather than maximum velocity (Vmax) discrimination governs the frequency of forming 2-aminopurine X cytosine base mispairs by DNA polymerase alpha. An in vitro system is used in which incorporation of dTMP or dCMP occurs opposite a template 2-aminopurine, and values for Km and Vmax are obtained. Results from a previous study in which dTTP and dCTP were competing simultaneously for insertion opposite 2-aminopurine indicated that dTMP is inserted 22 times more frequently than dCMP. We now report that the ratio of Km values KCm/KTm = 25 +/- 6, which agrees quantitatively with the dTMP/dCMP incorporation ratio obtained previously. We also report that VCmax is indistinguishable from VTmax. These Km and Vmax data are consistent with predictions from a model, the Km discrimination model, in which replication fidelity is determined by free energy differences between matched and mismatched base pairs. Central to this model is the prediction that the ratio of Km values for insertion of correct and incorrect nucleotides specifies the insertion fidelity, and the maximum velocities of insertion are the same for both nucleotides.


Asunto(s)
2-Aminopurina/metabolismo , Adenina/análogos & derivados , Replicación del ADN , ADN Polimerasa Dirigida por ADN/metabolismo , Animales , Bovinos , Humanos , Enlace de Hidrógeno , Cinética , Relación Estructura-Actividad , Especificidad por Sustrato , Termodinámica
8.
J Virol ; 45(3): 1028-36, 1983 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-6300444

RESUMEN

Abelson murine leukemia virus (A-MuLV) encodes a single protein with tyrosine kinase activity that can transform fibroblast cell lines in vitro and lymphoid target cells in vitro and in vivo. Expression of kinase-active A-MuLV protein can result in a deleterious effect on transformed fibroblast populations, leading to cell death or selection for nonlethal mutants of the virus. These mutants retain expression of the kinase activity but have lost large portions of the carboxy terminus of the Abelson protein. To more precisely map the sequences involved in this lethal effect, we have isolated a series of site-directed deletions from a DNA clone of the P160 wild-type strain of A-MuLV. In addition, a number of unexpected, spontaneous deletions occurring during transfection of NIH 3T3 cells were isolated. These deletions result in expression of carboxy-terminal truncated forms of the A-MuLV protein ranging from 130,000 to 84,000 in molecular weight. Analysis of the transforming and lethal activities of each mutant recovered in its RNA viral form shows that the transformation-essential and lethal-essential sequences do not overlap. These data and our previous work suggest that a function carried by the carboxy-terminal region of the A-MuLV protein acts in cis with the kinase-essential region to mediate the lethal effect.


Asunto(s)
Virus de la Leucemia Murina de Abelson/genética , Transformación Celular Viral , Genes Virales , Virus de la Leucemia Murina/genética , Proteínas Quinasas/genética , Animales , Secuencia de Bases , Supervivencia Celular , Ratones , Oncogenes , Proteínas Quinasas/fisiología , Proteínas Tirosina Quinasas
9.
Basic Life Sci ; 20: 213-29, 1982.
Artículo en Inglés | MEDLINE | ID: mdl-7115267

RESUMEN

We consider the role of unfavored tautomers in causing base-substitution transition mutations. Data obtained with the base analogue 2-aminopurine (AP) for the frequency of forming AP.T and AP.C base mispairs can be shown to be in probable conflict with tautomer model predictions. An alternative model, in which individual hydrogen bonds exhibit different bond strengths depending upon their ring position, is proposed to account for the frequencies of forming correct and incorrect base pairs. In this "differential H-bonding" model, disfavored tautomers of AP and those of common nucleotides play a generally insignificant role. A hydrogen-bonding free energy scale is derived in which free energy differences are obtained for all possible matched and mismatched base pairs. We also show that recent in vitro data for the formation of AP.C base pairs are consistent with a "passive polymerase" theoretical model in which base selection is governed not by the enzyme but by differences in base-pairing free energies.


Asunto(s)
Replicación del ADN , ADN Polimerasa Dirigida por ADN/metabolismo , Mutación , 2-Aminopurina/farmacología , Enlace de Hidrógeno , Modelos Biológicos , Mutación/efectos de los fármacos , Relación Estructura-Actividad , Moldes Genéticos , Termodinámica
10.
Cell ; 37(3): 1035-42, 1984 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-6204766

RESUMEN

The v-abl protein is known to be a tyrosine-specific protein kinase. However, its normal cellular homolog, c-abl P150, is not detectably phosphorylated on tyrosine in vivo or in vitro. The lack of associated tyrosine kinase activity for the c-abl protein seems paradoxical since it is the c-abl-derived sequences of the v-abl protein that encode the kinase activity. We have detected an altered human c-abl protein (P210) with associated tyrosine kinase activity in the K562 leukemia cell line. K562 cells are known to have a 9:22 chromosomal translocation involving the c-abl locus and have amplified the c-able gene 4 to 8 fold. The altered P210 human c-abl is serologically and structurally related to the normal c-abl protein. A structural alteration of the human c-abl protein. K562 cells may have unmasked its associated tyrosine kinase activity. This altered c-abl protein may have important implications for a mechanism of activation of this oncogene.


Asunto(s)
Transformación Celular Viral , Leucemia Experimental/genética , Oncogenes , Proteínas Quinasas/genética , Animales , ADN de Neoplasias/genética , Regulación de la Expresión Génica , Humanos , Leucemia Experimental/enzimología , Proteínas de Neoplasias/genética , Fragmentos de Péptidos/análisis , Fosfoproteínas/fisiología , Fosfotirosina , Proteínas Tirosina Quinasas , Tirosina/análogos & derivados , Tirosina/metabolismo
11.
J Virol ; 51(3): 620-7, 1984 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-6088787

RESUMEN

Abelson murine leukemia virus encodes a transforming protein which contains tyrosine kinase activity and is phosphorylated in vivo and in vitro. We found that P160 and P160-derived virus strains expressed an additional, altered v-abl protein which could not be phosphorylated. The altered v-abl protein (L-v-abl) differed from the phosphorylated form (K-v-abl) in that it was glycosylated and localized exclusively to the membrane fraction. Tunicamycin inhibition of N-linked carbohydrate addition did not restore phosphorylation. It did, however, reveal that L-v-abl had additional sequences relative to K-v-abl. The coding sequences required for this region and for the expression of L-v-abl were identified by replacing sequences in the P120 virus genome, which did not express L-v-abl, with sequences from the P160 virus genome. The necessary sequences were localized to the Moloney murine leukemia virus-derived gag gene. Comparison between the in vitro altered P120 and wild-type P120 virus strains indicated that expression of L-v-abl did not increase the efficiency of lymphoid transformation. Although the biological role of L-v-abl is not clear, our analyses have revealed that a specific amino terminal gag sequence can prevent v-abl from acting as a kinase substrate and can alter the cellular localization and modification of v-abl. These properties distinguish L-v-abl from previously reported v-abl proteins.


Asunto(s)
Virus de la Leucemia Murina de Abelson/genética , Antígenos Virales/genética , Transformación Celular Viral , Glicoproteínas/genética , Virus de la Leucemia Murina/genética , Proteínas Virales/genética , Animales , Secuencia de Bases , Células Cultivadas , Productos del Gen gag , Genes , Genes Virales , Ratones , Ratones Endogámicos , Plásmidos , Proteínas Quinasas/genética , Procesamiento Proteico-Postraduccional , Proteínas Tirosina Quinasas , Tunicamicina/farmacología
12.
J Periodontal Res ; 26(5): 440-51, 1991 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-1832457

RESUMEN

In a multicenter study of the effects of tetracycline (TC) fiber therapy, subgingival plaque samples were tested for 6 probable periodontal pathogens by DNA probe analysis. Levels of Actinobacillus actinomycetemcomitans, Eikenella corrodens, Fusobacterium nucleatum, Porphyromonas (Bacteroides) gingivalis, Prevotella intermedia (Bacteroides intermedius), and Wolinella recta were quantitatively determined in samples taken at baseline, and immediately after TC fiber removal, control fiber removal, and scaling and root planing. At untreated sites, samples were taken at baseline and 10 d later. Specificity of the DNA probe method was evaluated by testing the hybridization to 83 reference cultures. Interaction of the F. nucleatum probe with Fusobacterium periodonticum, and of the W. recta probe with Wolinella curva were the only cross-hybridizations noted. Species were detected at an average sensitivity of 2.9 x 10(4) organisms per sample. Approximately 70% of sites were initially infected with P. gingivalis and F. nucleatum; 50% with P. intermedia and E. corrodens; infections with W. recta and A. actinomycetemcomitans were less common (36% and 11% respectively). The average numbers of organisms found in the plaque samples were highest for F. nucleatum, P. gingivalis, and P. intermedia (ca. 10(6)). E. corrodens, W. recta, and A. actinomycetemcomitans occurred at 10-fold lower levels. Bacterial numbers and proportions of species in subgingival sites from the five centers did not differ appreciably. Both TC fiber therapy and scaling decreased the number of sites infected with all the monitored species. The bacterial composition at untreated sites and at sites where control fibers were placed was not significantly altered. The percentage reduction of the number of sites with detectable infection varied with each species: from 86% with W. recta to approximately 40% with P. gingivalis. Significant reduction of pocket depth and bleeding occurred at TC fiber-treated sites infected with each of the species. Significant attachment level gain occurred only at sites initially infected with P. gingivalis and treated with TC fibers.


Asunto(s)
Bacterias Anaerobias/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Enfermedades Periodontales/tratamiento farmacológico , Tetraciclina/farmacología , Actinobacillus/efectos de los fármacos , Bacteroides/efectos de los fármacos , Sondas de ADN , ADN Bacteriano/análisis , Eikenella corrodens/efectos de los fármacos , Fusobacterium/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Enfermedades Periodontales/microbiología , Polivinilos , Tetraciclina/administración & dosificación
13.
J Clin Microbiol ; 25(5): 845-8, 1987 May.
Artículo en Inglés | MEDLINE | ID: mdl-2438302

RESUMEN

Six mouse hybridomas secreting monoclonal antibodies specific for the glycoproteins of human immunodeficiency virus were developed. All six antibodies reacted by radioimmunoprecipitation with the glycoprotein precursor of 150,000 daltons as well as one of the proteolytic processing products of 110,000 daltons (gp110) or 41,000 daltons (gp41). Recombinant polypeptides spanning the env coding region were used to locate epitopes on the glycoprotein molecule. The panel of antibodies detected two distinct epitopes of gp41 and one epitope of gp110. We used the antibodies in indirect immunofluorescence assays to evaluate 13 clinical isolates of human immunodeficiency virus from diverse geographic regions, and we found that the gp110 epitope was recognized on all tested isolates, whereas the two gp41 epitopes were detected on 10 of 13 and 4 of 13 isolates.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Antígenos Virales/inmunología , VIH/inmunología , Proteínas del Envoltorio Viral/inmunología , Línea Celular , Electroforesis en Gel de Poliacrilamida , Epítopos/inmunología , Técnica del Anticuerpo Fluorescente , Glicoproteínas/inmunología , Anticuerpos Anti-VIH , Antígenos VIH , Humanos , Hibridomas , Inmunodifusión , Técnicas para Inmunoenzimas , Técnicas Inmunológicas
14.
J Clin Microbiol ; 28(2): 319-23, 1990 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-2312676

RESUMEN

Oligodeoxynucleotide probes were developed for identification of the periodontal bacteria Actinobacillus actinomycetemcomitans, Bacteroides gingivalis, B. intermedius types I and II, B. forsythus, Eikenella corrodens, Fusobacterium nucleatum, Haemophilus aphrophilus, Streptococcus intermedius, and Wolinella recta. Probes were designed by sequencing the 16S rRNA for each bacterium, identifying hypervariable regions, and chemically synthesizing species-specific probes. These probes were specific when tested against a panel of nucleic acids from closely related bacteria.


Asunto(s)
Bacterias/aislamiento & purificación , Sondas de ADN , Enfermedades Periodontales/microbiología , Bacterias/genética , Secuencia de Bases , Placa Dental/microbiología , Humanos , Datos de Secuencia Molecular , Boca/microbiología , ARN Ribosómico 16S/genética , Especificidad de la Especie
15.
Proc Natl Acad Sci U S A ; 82(6): 1810-4, 1985 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-3856862

RESUMEN

The Philadelphia chromosome (Ph1), observed in greater than 90% of chronic myelogenous leukemia (CML) patients, results from a specific chromosomal translocation involving the c-abl gene. The translocation breakpoint occurs near c-abl and correlates with the production of an altered c-abl mRNA. In the CML-derived cell line K562, Ph1 is accompanied by a structurally altered c-abl protein (P210c-abl) with in vitro tyrosine kinase activity not detected with the normal c-abl protein (P145c-abl). We have examined c-abl proteins in other Ph1-positive CML cell lines and found that they all express P210c-abl. P210c-abl was also detected in bone marrow cells from CML patients with Ph1 in the accelerated and blast crisis phases of the disease. Comparison of the [35S]methionine-labeled tryptic peptides generated from the normal P145c-abl and P210c-abl showed that they have closely related structures, but additional polypeptide sequences are present in P210c-abl. Based on these results we propose that translocation of c-abl in Ph1-positive CML results in the creation of a chimeric gene leading to the production of a structurally altered c-abl protein with activated tyrosine kinase activity. The altered P210 c-abl protein is strongly implicated in the pathogenesis of CML.


Asunto(s)
Leucemia Mieloide/genética , Proteínas de Neoplasias/genética , Línea Celular , Quimera , Cromosomas Humanos 21-22 e Y , Humanos , Leucemia Mieloide/metabolismo , Oncogenes , Proteínas Quinasas/genética , Proteínas Tirosina Quinasas , Translocación Genética
16.
Bioconjug Chem ; 2(6): 441-6, 1991.
Artículo en Inglés | MEDLINE | ID: mdl-1666839

RESUMEN

A novel dATP analogue, 3-[5-[(N-biotinyl-6- amiocaproyl)amino]pentyl]-1-(2-deoxy-beta-D-erythro-pentofuranosyl )-1H-pyrazolo[3,4-d]pyrimidin-4-amine 5'-triphosphate (9, bio-13-dAPPTP), which is modified at the 3-position with a flexible linker arm bearing a terminal biotin moiety, has been synthesized. This nucleotide is readily incorporated into DNA probes by nick translation. These probes hybridize to complementary targets as well as probes labeled with bio-dUTP, as judged by slot blot. When incorporated into oligonucleotides, they do not cause the loss of hybridization efficiency that an N-6-substituted adenine nucleotide does when incorporated into the same sites in the oligonucleotide.


Asunto(s)
Adenosina Trifosfato/análogos & derivados , Biotina , Biotina/análogos & derivados , Sondas de ADN , Pirazoles/síntesis química , Pirimidinas/síntesis química , Adenosina Trifosfato/síntesis química , Adenosina Trifosfato/metabolismo , Secuencia de Bases , Biotina/síntesis química , Biotina/metabolismo , ADN Polimerasa I/metabolismo , Sondas de ADN/química , Sondas de ADN/metabolismo , ADN Viral , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , Nucleótidos/metabolismo , Papillomaviridae/genética , Pirazoles/metabolismo , Pirimidinas/metabolismo , Temperatura
17.
J Virol ; 51(1): 223-32, 1984 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-6610061

RESUMEN

Antisera specific for six regions of the v- abl protein were used to serologically characterize the Abelson murine leukemia virus tyrosine kinase. Chemically synthesized peptides corresponding to the predicted v- abl protein sequence and larger regions of the v- abl protein expressed as fusion proteins in bacteria were used as immunogens. The specificity of each antiserum was confirmed by immunoprecipitation analysis with defined deletion mutants of Abelson murine leukemia virus. Several of these v- abl -specific antisera display much higher titers and avidities than serum harvested from mice bearing Abelson murine leukemia virus-induced tumors, previously the only source of anti- abl -specific serum. Two antisera were found to block the in vitro autophosphorylation of the v- abl protein as well as its ability to phosphorylate a peptide substrate. Examination of the sites against which the kinase-blocking antisera were prepared revealed that both are in close proximity to the in vivo sites of tyrosine phosphorylation, which fall within the region of high homology with v-src and other tyrosine kinases. Antisera directed against other regions of v- abl did not inhibit kinase activity.


Asunto(s)
Sueros Inmunes , Inhibidores de Proteínas Quinasas , Proteínas Virales/inmunología , Virus de la Leucemia Murina de Abelson/genética , Animales , ADN Viral/análisis , Ratones , Fosforilación , Plásmidos , Proteínas Tirosina Quinasas , Proteínas del Envoltorio Viral/inmunología , Proteínas Virales de Fusión
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