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PubMed1993

Assembly of the U2 small nuclear ribonucleoprotein from Trypanosoma brucei. A mutational analysis.

trans-Splicing in trypanosomes requires the functions of U2 and U4/U6 small nuclear (sn) RNPs. We have analyzed protein binding and assembly of the Trypanosoma brucei U2 snRNP, using specific antibodies against U2 snRNP proteins and in vitro reconstitution assays of U2 deletion derivatives and human-trypanosome hybrid RNAs. Stable binding of both the U2-specific 40-kDa and the common proteins requires only the 3'-terminal domain (stem-loop IIb, single-stranded region, and stem-loop IV), with loop IV providing the critical sequence determinant; stem-loop IV suffices for binding of the 40 kDa-protein, but not of the common proteins; surprisingly, the sequence of the "Sm-analogous" single-stranded region between stem-loops IIb and IV is not essential for protein binding. Our mutational analysis further indicates that interactions between common and specific proteins play an important role in the assembly of a stable core complex. Finally, a partially assembled U2 RNP complex could be identified as a kinetic intermediate of U2 snRNP assembly. We propose a model of the domain structure and assembly of the trans-spliceosomal U2 snRNP, which deviates in several aspects from that of the cis-spliceosomal U2 snRNP; these differences may be related to the trans-splicing-specific functions of the trypanosomal U2 snRNP.

Animals↗

PubMed2005

Computed tomography and 18F-FDG positron emission tomography for therapy control of Hodgkin's and non-Hodgkin's lymphoma patients: when do we really need FDG-PET?

BACKGROUND: The aim of this study was to evaluate the accuracy of computed tomography (CT) and [(18)F]fluoro-deoxy-d-glucose positron emission tomography (FDG-PET) for prediction of progression-free survival of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) patients after completion of therapy. PATIENTS AND METHODS: CT and FDG-PET were performed in 40 HD, 17 indolent NHL and 44 aggressive NHL patients (29 women, 72 men; aged 41+/-14 years) in a median of 2 months after therapy. Progression-free survival was evaluated using the Kaplan-Meier method. Independent prognostic factors were identified by means of Cox proportional hazards model. RESULTS: CT imaging results were progressive disease (PD) in five, stable disease (SD) in 57, and partial response (PR) or complete remission (CR) in 39 patients. FDG-PET suggested residual lymphoma in 24 patients. Three-year progression-free survival rates after exclusion of five PD patients were: 100% (PET negative; CT: PR or CR), 81% (PET negative; CT: SD), 21% (PET positive; CT: SD) and 0% (PET positive; CT: PR). FDG-PET (P<0.0001) and bulky disease (P <0.05) were identified as independent prognostic variables. CONCLUSIONS: Among lymphoma patients with PR and SD on CT, FDG-PET discriminated those destined to progress into a low risk of < or =20% and a high risk for recurrence of > or =80%.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

A new approach to spatial covariance modeling of functional brain imaging data: ordinal trend analysis.

In neuroimaging studies of human cognitive abilities, brain activation patterns that include regions that are strongly interactive in response to experimental task demands are of particular interest. Among the existing network analyses, partial least squares (PLS; McIntosh, 1999; McIntosh, Bookstein, Haxby, & Grady, 1996) has been highly successful, particularly in identifying group differences in regional functional connectivity, including differences as diverse as those associated with states of awareness and normal aging. However, we address the need for a within-group model that identifies patterns of regional functional connectivity that exhibit sustained activity across graduated changes in task parameters. For example, predictions of sustained connectivity are commonplace in studies of cognition that involve a series of tasks over which task difficulty increases (Baddeley, 2003). We designed ordinal trend analysis (OrT) to identify activation patterns that increase monotonically in their expression as the experimental task parameter increases, while the correlative relationships between brain regions remain constant. Of specific interest are patterns that express positive ordinal trends on a subject-by-subject basis. A unique feature of OrT is that it recovers information about functional connectivity based solely on experimental design variables. In particular, there is no requirement by OrT to provide either a quantitative model of the uncertain relationship between functional brain circuitry and subject variables (e.g., task performance and IQ) or partial information about the regions that are functionally connected. In this letter, we provide a step-by-step recipe of the computations performed in the new OrT analysis, including a description of the inferential statistical methods applied. Second, we describe applications of OrT to an event-related fMRI study of verbal working memory and H(2)15O-PET study of visuo-motor learning. In sum, OrT has potential applications to not only studies of young adults and their cognitive abilities, but also studies of normal aging and neurological and psychiatric disease.

Adult↗

PubMed2003

Intra- and postoperative predictors of stroke after coronary artery bypass grafting.

BACKGROUND: Stroke is a devastating complication of coronary artery bypass graft surgery. An individual's risk of stroke is based in part on preoperative characteristics but also on intra- and postoperative factors. We developed a risk prediction model for stroke based on factors in intra- and postoperative care, after adjusting for a patient's preoperative risk. METHODS: We conducted a regional prospective study of 11,825 consecutive patients undergoing coronary artery bypass graft surgery surgery from 1996 to 2001. Data were collected on patient and disease characteristics, intra- and postoperative care and course, and outcomes. Stroke was defined as "a new focal neurologic deficit which appears and is still at least partially evident more than 24 hours after its onset." Logistic regression identified significant predictors of stroke. RESULTS: The incidence of stroke was 1.5%. The regression model significantly predicted the occurrence of stroke. As compared with cardiopulmonary bypass for less than 90 minutes, cardiopulmonary bypass for 90 to 113 minutes, odds ratio = 1.59, p = 0.022), cardiopulmonary bypass for 114 minutes or more (odds ratio = 2.36, p < 0.001), atrial fibrillation (odds ratio = 1.82, p < 0.001), and prolonged inotrope use (odds ratio = 2.59, p = 0.001) significantly improved our ability to predict stroke. Nearly 75% of all strokes occurred among the 90% of patients at low or medium preoperative risk. CONCLUSIONS: The inclusion of factors associated with intra- and postoperative care and course significantly improved the prediction model. Most strokes occurred among patients at low or medium preoperative risk, suggesting that many of these strokes may be preventable. Reduction in stroke risk may require modifications in intra- and postoperative care and course.

Age Distribution↗

PubMed1999

Conserved features of Y RNAs revealed by automated phylogenetic secondary structure analysis.

Y RNAs are small 'cytoplasmic' RNAs which are components of the Ro ribonucleoprotein (RNP) complex. The core of this complex, which is found in the cell nuclei of higher eukaryotes as well as the cytoplasm, is composed of a complex between the 60 kDa Ro protein and Y RNAs. Human cells contain four distinct Y RNAs (Y1, Y3, Y4 and Y5), while other eukaryotes contain a variable number of Y RNA homologues. When detected in a particular species, the Ro RNP has been present in every cell type within that particular organism. This characteristic, along with its high conservation among vertebrates, suggests an important function for Ro RNP in cellular metabolism; however, this function has not yet been definitively elucidated. In order to identify conserved features of Y RNA sequences and structures which may be directly involved in Ro RNP function, a phylogenetic comparative analysis of Y RNAs has been performed. Sequences of Y RNA homologues from five vertebrate species have been obtained and, together with previously published Y RNA sequences, used to predict Y RNA secondary structures. A novel RNA secondary structure comparison algorithm, the suboptimal RNA analysis program, has been developed and used in conjunction with available algorithms to find phylogenetically conserved secondary structure models for YI, Y3 and Y4 RNAs. Short, conserved sequences within the Y RNAs have been identified and are invariant among vertebrates, consistent with a direct role for Y RNAs in Ro function. A subset of these are located wholly or partially in looped regions in the Y3 and Y4 RNA predicted model structures, in accord with the possibility that these Y RNAs base pair with other cellular nucleic acids or are sites of interaction between the Ro RNP and other macromolecules.

Animals↗

PubMed2005

The loop C region of the murine 5-HT3A receptor contributes to the differential actions of 5-hydroxytryptamine and m-chlorophenylbiguanide.

Sequence and predicted structural similarities between members of the Cys loop superfamily of ligand-gated ion channel receptors and the acetylcholine binding protein (AChBP) suggest that the ligand-binding site is formed by six loops that intersect at subunit interfaces. We employed site-directed mutagenesis to investigate the role of amino acids from the loop C region of the murine 5-HT(3AS)R in interacting with two structurally different agonists, serotonin (5-HT) and m-chlorophenylbiguanide (mCPBG). Mutant receptors were evaluated using radioligand binding, two-electrode voltage clamp, and immunofluorescence studies. Electrophysiological assays were employed to identify changes in response characteristics and relative efficacies of mCPBG and the partial agonist, 2-methyl 5-HT (2-Me5-HT). We have also constructed novel 5-HT and mCPBG docked models of the receptor binding site based on homology models of the AChBP. Both ligand-docked models correlate well with results from mutagenesis and electrophysiological assays. Four key amino acids were identified as being important to ligand binding and/or gating of the receptor. Among these, I228 and D229 are specific for effects mediated by 5-HT compared to mCPBG, indicating a differential interaction of these ligands with loop C. Residues F226 and Y234 are important for both 5-HT and mCPBG interactions. Mutations at F226, I228, and Y234 also altered the relative efficacies of agonists, suggesting a role in the gating mechanism.

Amino Acid Sequence↗

PubMed1987

Muscle models: what is gained and what is lost by varying model complexity.

Three structurally different types of models have evolved over the years to describe muscle-joint systems. The first, based on an input-output analysis of a given task, results in a simple second-order differential equation description that is adequate over a certain movement operating range. The second, based on the classic structural model of Hill (1938), results in a higher-order nonlinear model described by ordinary differential equations. The third, based on an analysis of the biophysical contractile mechanism, results in a complex partial differential equation description. The advantages and disadvantages of each type of model are considered, based on the criteria of identifying the simplest model that can adequately simulate any fundamental type of human movement without modifying model parameters for different tasks. It is shown that an eighth-order Hill-based antagonistic muscle-joint model is able to satisfy these criteria for a given joint if each of the four basic mechanically-significant non-linearities of the system are included in the model. This same model structure has been used successfully for eight different muscle-joint systems, ranging in size from knee flexion-extension to eye rotation--the only difference between the models is in the parameter values. Second-order models are shown to be task-specific special cases of the input-output behavior of the eighth-order model, while the more complex biophysical models are hypothesized to have insignificant advantages and many disadvantages over the Hill-based model during normal human movement.

Animals↗

PubMed1998

Mixed quantitative/qualitative modeling and simulation of the cardiovascular system.

The cardiovascular system is composed of the hemodynamical system and the central nervous system (CNS) control. Whereas the structure and functioning of the hemodynamical system are well known and a number of quantitative models have already been developed that capture the behavior of the hemodynamical system fairly accurately, the CNS control is, at present, still not completely understood and no good deductive models exist that are able to describe the CNS control from physical and physiological principles. The use of qualitative methodologies may offer an interesting alternative to quantitative modeling approaches for inductively capturing the behavior of the CNS control. In this paper, a qualitative model of the CNS control of the cardiovascular system is developed by means of the fuzzy inductive reasoning (FIR) methodology. FIR is a fairly new modeling technique that is based on the general system problem solving (GSPS) methodology developed by G.J. Klir (Architecture of Systems Problem Solving, Plenum Press, New York, 1985). Previous investigations have demonstrated the applicability of this approach to modeling and simulating systems, the structure of which is partially or totally unknown. In this paper, five separate controller models for different control actuations are described that have been identified independently using the FIR methodology. Then the loop between the hemodynamical system, modeled by means of differential equations, and the CNS control, modeled in terms of five FIR models, is closed, in order to study the behavior of the cardiovascular system as a whole. The model described in this paper has been validated for a single patient only.

Central Nervous System↗

PubMedDate not supplied

QSARs for 6-azasteroids as inhibitors of human type 1 5alpha-reductase: prediction of binding affinity and selectivity relative to 3-BHSD.

Quantitative structure-activity relationships (QSARs) are developed to describe the ability of 6-azasteroids to inhibit human type 1 5alpha-reductase. Models are generated using a set of 93 compounds with known binding affinities (K(i)) to 5alpha-reductase and 3beta-hydroxy-Delta(5)-steroid dehydrogenase/3-keto-Delta(5)-steroid isomerase (3-BHSD). QSARs are generated to predict K(i) values for inhibitors of 5alpha-reductase and to predict selectivity (S(i)) of compound binding to 3-BHSD relative to 5alpha-reductase. Log(K(i)) values range from -0.70 log units to 4.69 log units, and log(S(i)) values range from -3.00 log units to 3.84 log units. Topological, geometric, electronic, and polar surface descriptors are used to encode molecular structure. Information-rich subsets of descriptors are identified using evolutionary optimization procedures. Predictive models are generated using linear regression, computational neural networks (CNNs), principal components regression, and partial least squares. Compounds in an external prediction set are used for model validation. A 10-3-1 CNN is developed for prediction of binding affinity to 5alpha-reductase that produces root-mean-square error (RMSE) of 0.293 log units (R(2) = 0.97) for compounds in the external prediction set. Additionally, an 8-3-1 CNN is generated for prediction of inhibitor selectivity that produces RMSE = 0.513 log units (R(2) = 0.89) for the external prediction set. Models are further validated through Monte Carlo experiments in which models are generated after dependent variable values have been scrambled.

Azasteroids↗

PubMed2004

Pursuit-evasion predator-prey waves in two spatial dimensions.

We consider a spatially distributed population dynamics model with excitable predator-prey kinetics, where species propagate in space due to their taxis with respect to each other's gradient in addition to, or instead of, their diffusive spread. Earlier, we have described new phenomena in this model in one spatial dimension, not found in analogous systems without taxis: reflecting and self-splitting waves. Here we identify new phenomena in two spatial dimensions: unusual patterns of meander of spirals, partial reflection of waves, swelling wave tips, attachment of free wave ends to wave backs, and as a result, a novel mechanism of self-supporting complicated spatiotemporal activity, unknown in reaction-diffusion population models.

Adaptation, Physiological↗

PubMed2005

Hierarchical multiscale mechanism development for methane partial oxidation and reforming and for thermal decomposition of oxygenates on Rh.

A thermodynamically consistent C1 microkinetic model is developed for methane partial oxidation and reforming and for oxygenate (methanol and formaldehyde) decomposition on Rh via a hierarchical multiscale methodology. Sensitivity analysis is employed to identify the important parameters of the semiempirical unity bond index quadratic exponential potential (UBI-QEP) method and these parameters are refined using quantum mechanical density functional theory. With adjustment of only two pre-exponentials in the CH4 oxidation subset, the C1 mechanism captures a multitude of catalytic partial oxidation (CPOX) and reforming experimental data as well as thermal decomposition of methanol and formaldehyde. We validate the microkinetic model against high-pressure, spatially resolved CPOX experimental data. Distinct oxidation and reforming zones are predicted to exist, in agreement with experiments, suggesting that hydrogen is produced from reforming of methane by H2O formed in the oxidation zone. CO is produced catalytically by partial oxidation up to moderately high pressures, with water-gas shift taking place in the gas-phase at sufficiently high pressures resulting in reduction of CO selectivity.

Journal Article↗

PubMedDate not supplied

Evaluation of amniotic membrane as adhesion prophylaxis in a novel surgical gastroschisis model.

Adhesions are a leading cause of bowel obstruction and infertility. The coverage of peritoneal defects, as in gastroschisis, is still a crucial problem. Despite biodegradable substitutes and synthetic implants such as PTFE membrane, a satisfactory replacement for gastroschisis has not been identified. The amniotic membrane, which is available at birth with a low antigenicity, was evaluated as a peritoneal substitute. Viable, partially viable, and inversed-used amniotic membranes were compared in a rat model. A full-thickness abdominal wall defect was made and the amniotic membrane sutured into this defect. The skin was closed over the amniotic membrane. Reoperation was performed 3 weeks after initial surgery, and the adhesion formation was measured by computerized area calculation. Viable amniotic membrane showed 0 to 3% area adhesion formation, while partially viable (50%) amniotic membrane demonstrated 33% area adhesion formation. Inversed-used amniotic membrane, with the stromal side directed toward the abdominal cavity, showed 70% of the amniotic membrane area to be covered with adhesions. The same amount was found in the control group, in which no substitute was sutured into the defect. This animal model is suitable for the straightforward evaluation of peritoneal substitutes with regard to adhesion formation. It is easy to perform and mimics surgical needs. Viable amniotic membrane proved to be an excellent antiadhesive tissue.

Abdominal Muscles↗

PubMedDate not supplied

A comparative QSAR study using CoMFA, HQSAR, and FRED/SKEYS paradigms for estrogen receptor binding affinities of structurally diverse compounds.

The three-dimensional quantitative structure-activity relationship (QSAR) technique of comparative molecular field analysis (CoMFA) has demonstrated the ability to provide accurate predictions for diverse chemical compounds when trained with molecules of diverse chemical type. Although predictive, the derivation and utilization of models of this type are quite computationally and person power intensive. It is this intensity that pragmatically limits the widespread implementation of these models as predictive tools. In this study, two newer QSAR techniques were evaluated as possible alternatives to CoMFA based QSAR models for the purpose of rapidly identifying estrogen receptor ligands from diverse collections of molecules. The first of these is Hologram QSAR, or HQSAR. HQSAR utilizes Tripos molecular fingerprints as descriptors in conjunction with partial least squares (PLS) regression and cross-validation routines. The HQSAR technique demonstrated the ability to rapidly develop QSAR models independent of the intense user input (i.e. geometry optimization, conformational analysis, and molecular superposition were not required). Second, a newly developed QSAR paradigm that utilizes Molecular Design Limited (MDL) substructure keys (SKEYS) as descriptors in combination with an evolutionary algorithm, Fast Random Elimination of Descriptors (FRED), was evaluated. By utilizing the FRED/SKEYS algorithm, a simple substructure-based QSAR model was derived that was comparable in statistical robustness and predictive ability to both CoMFA and HQSAR derived models. A comparison of the utility of these three approaches as computational tools for the rapid identification of estrogen receptor ligands as potential endocrine disruptors as assessed by model predictive ability will be described.

Algorithms↗

PubMed2004

Characterization of glucose transporter 8 (GLUT8) in the ovine placenta of normal and growth restricted fetuses.

Facilitated glucose transporters (GLUTs) in the chorionic epithelium are primary conduits for glucose delivery to placental and fetal tissues. The objective of this study was to characterize GLUT8 in the ovine placenta and determine if differences in mRNA and protein concentrations occur in an ovine model of intrauterine growth restriction (IUGR). A GLUT8 partial mRNA was generated, which shares 95 per cent identity with bovine GLUT8 nucleotide sequence. Northern hybridization identified a 2.1 kilobase transcript. GLUT8 mRNA concentrations normalized to beta-actin mRNA concentrations increased during late gestation. Western immunoblots with an affinity-purified anti-mouse GLUT8 antiserum detected GLUT8 in late gestation ovine placenta plasma membranes. GLUT8 was immunolocalized to the chorionic epithelial layer and uterine epithelial cells from mid to late gestation. GLUT8 mRNA and protein concentrations at 135 days gestational age were decreased by 34.8 per cent and 21.8 per cent, respectively (P<0.05), in an ovine placental insufficiency model of IUGR. Identification of GLUT8 in the ovine placenta indicates a potential role for GLUT8 in mediating glucose uptake within the placenta and transport to the fetus. Further studies are necessary to confirm this hypothesis and whether the observed decreases in GLUT8 in the PI-IUGR model might contribute, at least in part, to the placental glucose transport deficit that occurs in this model.

Actins↗

PubMed2003

Impact of multiple cation-pi interactions upon calix[4]arene substrate binding and specificity.

The cation-pi interaction influence on the conformation and binding of calix[4]arenes to alkali-metal cations has been studied using a dehydroxylated model. The model allows for the separation of cooperative cation-pi and electrostatic forces commonly found in the binding motifs found in calixarene complexes. Starting from the four well-known calix[4]arene conformations, six conformers for this dehydroxylated model (cone, partial cone, flattened cone, chair, 1,2-alternate, and 1,3-alternate) have been characterized by geometry optimization and frequency analysis using the Becke three-parameter exchange functional with the nonlocal correlation functional of Lee, Yang, and Parr and the 6-31G(d) basis set. Without the stabilization provided by the hydroxyl hydrogen bonds in calix[4]arene, neither the cone nor the 1,2-alternate conformation is computed to be a ground-state structure. The partial cone, flattened cone, chair, and 1,3-alternate conformers have been identified as ground-state structures in a vacuum, with the partial cone and the 1,3-alternate as the lowest energy minima in the aromatic model. The C(4)(v)() cone conformation is found to be a transition structure separating the flattened cone (C(2)(v)()) conformers. The energetic and structural preferences of the calix[4]arene model change dramatically when it is bound to Li(+), Na(+), and K(+). The number of pi-faces, the positioning of these pi-faces with respect to the cations, and the nature of the cation were studied as factors in the binding strength. A detailed study of the distances and angles between the aromatic ring centroids and the cations reveals the energetic advantages of multiple weak cation-pi interactions. The geometries are often far from the optimal cation-pi interaction in which the cation approaches in a perpendicular path the aromatic ring center, where the quadrupole moment is strongest. The results reveal that multiple weaker nonoptimal cation-pi interactions contribute significantly to the overall binding strength. This theoretical analysis underscores the importance of neighboring aromatic faces and provides new insight into the significance of cation-pi binding, not only for calix[4]arenes, but also for other supramolecular and biological systems.

Journal Article↗

PubMed2000

Molecular weight, structure, and shape of oat (1-->3),(1-->4)-beta-D-glucan fractions obtained by enzymatic degradation with lichenase.

Oat beta-glucan was partially degraded by lichenase for different periods of time. Weight-average molecular weights were obtained from SEC-RI-RALLS-Visc and ranged from 5300 to 257,200. Weight-average intrinsic viscosities ranged from 7 to 160 mL/g. The determined viscosity equation, [eta] = 5.47 x 10(-3) M 0.82, indicated an extended coil conformation. When the coil was modeled as a wormlike chain a persistent length of 2.30 nm was obtained. 1H and 13C NMR spectroscopy were used to identify the structural units in the partially degraded beta-glucan. The identification of the disaccharide laminaribiose in the hydrolysates may suggest the presence of a new structural feature in cereal beta-glucan.

Avena↗

PubMed1998

Genetic analysis of Xenopus transcription factor IIIA.

We describe a method for the genetic analysis of the DNA-binding properties of Xenopus transcription factor IIIA (TFIIIA). In this approach, a transcriptional activator with the DNA-binding specificity of Xenopus TFIIIA is expressed in yeast cells, where it specifically activates expression of a beta-galactosidase reporter gene containing one or more Xenopus 5 S rRNA genes that function as upstream activator sequences. This transcription-promoting activity was used as the basis for a genetic assay of Xenopus TFIIIA's DNA-binding function in yeast, an assay that we show can be calibrated quantitatively to allow the affinity of the Xenopus TFIIIA-5 S rRNA gene interaction to be deduced from measurements of beta-galactosidase activity. We have combined this genetic assay with a simple and efficient method of mutagenesis that makes use of error-prone PCR and homologous recombination to generate and screen large numbers of TFIIIA mutants for those with altered 5 S rRNA gene-binding affinity. Over 30 such mutants have been identified and partially characterized. The mutants we have obtained provide strong support for the application to intact TFIIIA of recent structural models of the N-terminal zinc fingers of the protein bound to fragments of the 5 S rRNA gene. Other mutants permit identification of important residues in more C-terminal zinc fingers of TFIIIA for which high-resolution structural information is not currently available. Finally, our results have interesting implications with respect to the mechanism of activation of transcription by RNA polymerase II in yeast.

Amino Acid Sequence↗

PubMed1986

Effects of tumor growth on host defenses.

Monocytes and macrophages play an important role in host defense against neoplasia. Studies from our and other laboratories have demonstrated that patients with a variety of cancers have a defect in monocyte chemotactic responses. Tumor-bearing mice are also inhibited in their ability to accumulate macrophages to inflammatory foci. We have shown that extracts prepared from murine tumors, as well as the plasma and urine of tumor-bearing mice, contain anti-inflammatory proteins which are antigenically and physicochemically related to the immunosuppressive retroviral envelope protein p15E. Similarly, proteins capable of inhibiting monocyte chemotactic responses are present in human cancerous effusions and can be specifically absorbed by monoclonal antibodies to p15E. Furthermore, we have demonstrated that human malignant and mitogen-transformed cells contain p15E-related antigens. These findings led us to propose a two stage model of tumorigenesis: the first stage involves neoplastic transformation of a cell while the second stage involves activation of a gene coding for a p15E-like protein which allows the transformed cell to escape immune surveillance and go on to become a tumor. Support for this model has come from recent studies which have identified within the human genome an endogenous retrovirus sequence whose envelope gene is partially homologous to a highly conserved region of p15E. Using a synthetic peptide, termed CKS-17, we have shown that this region may be responsible for many of the biological activities of p15E and is capable of suppressing lymphocyte and natural killer cell immune functions as well as those of monocytes and macrophages. Thus tumors may be capable of evading host defense mechanisms by activation of a normal gene related to the immunosuppressive retroviral protein p15E.

Animals↗