Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “virtual screening”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,207 records · Page 67Linked to original sources
PubMedDate not supplied

Ototoxicity: an argument for evaluation of the cochlea in safety testing in animals.

The cochlea is one of the more common targets for toxic effects, yet current toxicologic screening in animals does not routinely evaluate the cochlea as a potential target organ. Although histopathologic sections are routinely taken from the eye and the optic nerve and tract and most studies include at least 1 section through the nasal cavity and olfactory mucosa, the cochlea is not histopathologically examined in routine toxicity studies. Unfortunately, routine clinical examinations frequently miss ototoxicity because rodents and other species can lose most of their high-frequency hearing and still respond to most ambient noises. Ototoxicity as a deficiency in toxicologic screening can be remedied by using well-established histopathologic and behavioral methods or electrophysiologic methods, such as brain stem auditory evoked responses (BAERs). Once the equipment is in place, BAERs can be obtained quickly and easily for ototoxicity screening (approximately 15 minutes for paired testing of 2 rats and 30 minutes each for dogs). BAERs also can be used in virtually all mammalian species. Three or 4 probe frequencies (eg, 4, 8, 16, and 32 kHz), representing different areas of the cochlea, can be tested in a few minutes with subcutaneous electrodes under short-acting chemorestraint. Given the availability of several approaches to screening for ototoxicity and the importance of the auditory function in human health, safety tests of chemicals and drugs should include an effective screening test for ototoxicity.

Animals↗
PubMed1997

Patient-specific anatomic models from three dimensional medical image data for clinical applications in surgery and endoscopy.

Virtual surgery and endoscopy use computer-generated volume renderings and/or models created from 3D medical image scans (CT or MRI) of individual patients. The patient's anatomy, including organs and other internal structures of interest, are then traversed in a virtual "fly-through," giving nearly the same visual impression as if the corresponding real organ was being examined intraoperatively, or as if an actual video or fiberoptic endoscopic procedure was being performed. Such virtual examinations may provide capabilities and information not possible or available in physical examinations. The potential is to provide a noninvasive computer-aided treatment plan or diagnostic screening procedure to augment or replace conventional invasive procedures. With sophisticated image processing and computational analysis, it is possible to perform realistic and useful simulations of surgical and endoscopic procedures, including "virtual dissection and resection" and "virtual biopsy." Surgical margins can be accurately assessed and differential tissue diagnoses made based upon spectral or other information contained in the patient-specific images and models.

Algorithms↗
PubMed2000

Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia.

Abetalipoproteinemia (ABL) is an inherited disease characterized by the virtual absence of apolipoprotein B (apoB)-containing lipoproteins from plasma. Only limited numbers of families have been screened for mutations in the microsomal triglyceride transfer protein (MTP) gene. To clarify the genetic basis of clinical diversity of ABL, mutations of the MTP gene have been screened in 4 unrelated patients with ABL. Three novel mutations have been identified: a frameshift mutation caused by a single adenine deletion at position 1389 of the cDNA, and a missense mutation, Asn780Tyr, each in homozygous forms; and a splice site mutation, 2218-2A-->G, in a compound heterozygous form. The frameshift and splice site mutations are predicted to encode truncated forms of MTP. When transiently expressed in Cos-1 cells, the Asn780Tyr mutant MTP bound protein disulfide isomerase (PDI) but displayed negligible MTP activity. It is of interest that the patient having the Asn780Tyr mutation, a 27-year-old male, has none of the manifestations characteristic of classic ABL even though his plasma apoB and vitamin E were virtually undetectable. These results indicated that defects of the MTP gene are the proximal cause of ABL.

Abetalipoproteinemia↗
PubMed1989

A comparison of two different T-grain films in rare-earth screens with a standard film-screen combination for intravenous pyelography and bone examinations.

T-grain film is claimed to give significantly improved image quality, allowing the use of faster screens without loss of quality and thus reducing radiation dose. We tested this claim for two systems. In each case comparison was made with our usual screen-film combination, Agfa Curix RP1 film with Kodak Xomatic Regular screens (a nominally 200 speed system). The systems tested were Kodak TMatG in Kodak Lanex Medium screens (300 speed) and Agfa STG in Kodak Lanex Regular screens (400 speed). The Agfa STG-Lanex Regular system performed less well than the standard system for intravenous pyelograms (IVPs), bones and soft-tissue detail. Its speed advantage was not apparent below 70 kV. The Kodak TMatG-Lanex Medium system was better than the standard system for IVPs but not as good for bones. It gave virtually no speed advantage below 90 kV. Kodak T-grain film in a medium-speed, rare-earth screen was found to be better than the standard system for IVPs. Agfa T-grain film in a fast rare-earth screen was unsatisfactory for IVPs. Neither combination was as good as the standard system for bones.

Bone and Bones↗
PubMed1983

Fetal and neonatal hydronephrosis.

Maternal ultrasonography makes it possible to easily detect hydronephrosis in the fetus, and therefore fetal "screening" should be part of every obstetrical ultrasonogram. However, the mere presence of fetal hydronephrosis virtually never means that either fetal intervention or early delivery is warranted. The importance of fetal case-finding is that it enables us to promptly (and electively) evaluate and treat the asymptomatic neonate before infection or other complications occur.

Female↗
PubMed2001

Image display technology and image processing.

Significant developments in video imaging have taken place but further progress is needed to provide images with the right characteristics for optimal interpretation by the operator. The nature and location of the image display in relation to the surgeon and operating field are also important in facilitating image-guided surgery/interventions, and several new technologies are being explored. In the diagnostic field, virtual reality surface anatomical and internal luminal rendering has opened a new chapter in diagnosis, screening, and treatment planning, the potential of which is only just being realized.

Diagnostic Imaging↗
PubMed1991

Purification, quantification and mechanical hatching of eggs of the tapeworm, Hymenolepis diminuta.

Eggs of Hymenolepis diminuta were separated from host's feces using a combination of NaCl flotation, filtration through nylon monofilament screen cloths, and centrifugation. The resulting purified egg preparations (PEPs) were verified microscopically to be virtually free of contaminating debris. The relationship of absorbance (500 nm) of PEPs and 'number of eggs per unit volume' was linear, and such measurements provided a rapid, reproducible method for quantifying PEPs. The average wet and dry weights of individual eggs were 2.86 x 10(-7) and 0.458 x 10(-7) g, respectively. Eggs were mechanically hatched using a Dounce homogenizer with pestle 'A'. This technique caused no detectable damage to larvae and resulted in a high percentage of 'activated' (i.e. motile) larvae.

Animals↗
PubMed1995

Stimulation, data acquisition, spikes detection and time/rate analysis with a graphical programming system: an application to vision studies.

A Macintosh-based system performs stimulus control and data acquisition, and an off-line analysis, in experiments on visually driven neurons in frog. The stimulus is a target moved on a modified XY recorder. The computer is equipped with a multifunction input/output board to perform stimulus control and data acquisition. The graphical programming system LabVIEW 2 was used to develop the 'Vision 93' package made of 4 main 'virtual instruments' (VIs). By means of DOCS-Exp, the user controls the experiment via screen displays which look like front panels of electronic instruments. DOCS-Preproc performs a user-controlled spike detection and computes mean impulse rate values. DOCS-SAS displays the instantaneous frequency, mean impulse rate, spike counts or interspike time intervals as staircase histograms and/or spline smoothed curves. Finally, DOCS-x-Functions computes and graphs quantitative stimulus/response relationships in terms of velocity, diameter, orientation and configuration of the target. The functionalities of these main VIs are presented and original software components are detailed. System operation is illustrated by using the successive VIs to process a sample signal record.

Algorithms↗
PubMed2005

Successful in silico discovery of novel nonsteroidal ligands for human sex hormone binding globulin.

Using "in silico" drug design methodologies, we have discovered several nonsteroidal compounds of natural origin that bind to human sex hormone binding globulin (SHBG) with affinity constants of 0.1 x 10(6) to 1.2 x 10(6) M(-1). The computational solutions we developed involved pharmacophore-aided database search, virtual protein-ligand docking, and structure-activity modeling with "inductive" QSAR descriptors. By screening 23 836 natural substance structures, we identified 29 potential SHBG ligands, and eight of these bound the protein in vitro. These nonsteroidal ligands belong to four classes of molecular scaffolds with several available substitution positions that could allow chemical modification to enhance SHBG-binding activity. Interestingly, one of these compounds is structurally similar to a dicyclohexane derivative that binds to rat SHBG and causes azospermia when administered to male rats. Taken together, the in silico strategy we have developed will aid in the discovery of nonsteroidal ligands of SHBG with novel pharmacological properties.

Algorithms↗
PubMed2002

Directed evolution of novel polymerase activities: mutation of a DNA polymerase into an efficient RNA polymerase.

The creation of novel enzymatic function is of great interest, but remains a challenge because of the large sequence space of proteins. We have developed an activity-based selection method to evolve DNA polymerases with RNA polymerase activity. The Stoffel fragment (SF) of Thermus aquaticus DNA polymerase I is displayed on a filamentous phage by fusing it to a pIII coat protein, and the substrate DNA template/primer duplexes are attached to other adjacent pIII coat proteins. Phage particles displaying SF polymerases, which are able to extend the attached oligonucleotide primer by incorporating ribonucleoside triphosphates and biotinylated UTP, are immobilized to streptavidin-coated magnetic beads and subsequently recovered. After four rounds of screening an SF library, three SF mutants were isolated and shown to incorporate ribonucleoside triphosphates virtually as efficiently as the wild-type enzyme incorporates dNTP substrates.

Amino Acid Sequence↗
PubMed2005

Calculation of proton-deuteron breakup reactions including the Coulomb interaction between the two protons.

The Coulomb interaction between the two protons is fully included in the calculation of proton-deuteron breakup with realistic interactions for the first time. The hadron dynamics is based on the purely nucleonic charge-dependent (CD) Bonn potential and its realistic extension CD Bonn +Delta to a coupled-channel two-baryon potential, allowing for single virtual Delta-isobar excitation. Calculations are done using integral equations in momentum space. The screening and renormalization approach is employed for including the Coulomb interaction. The Coulomb effect on breakup observables is seen at all energies in particular kinematic regimes.

Journal Article↗
PubMed2003

Time dependent ethnic convergence in colorectal cancer survival in Hawaii.

BACKGROUND: Although colorectal cancer death rates have been declining, this trend is not consistent across all ethnic groups. Biological, environmental, behavioral and socioeconomic explanations exist, but the reason for this discrepancy remains inconclusive. We examined the hypothesis that improved cancer screening across all ethnic groups will reduce ethnic differences in colorectal cancer survival. METHODS: Through the Hawaii Tumor Registry 16,424 patients diagnosed with colorectal cancer were identified during the years 1960-2000. Cox regression analyses were performed for each of three cohorts stratified by ethnicity (Caucasian, Japanese, Hawaiian, Filipino, and Chinese). The models included stage of diagnosis, year of diagnosis, age, and sex as predictors of survival. RESULTS: Mortality rates improved significantly for all ethnic groups. Moreover, with the exception of Hawaiians, rates for all ethnic groups converged over time. Persistently lower survival for Hawaiians appeared linked with more cancer treatment. CONCLUSION: Ethnic disparities in colorectal cancer mortality rates appear primarily the result of differential utilization of health care. If modern screening procedures can be provided equally to all ethnic groups, ethnic outcome differences can be virtually eliminated.

Adult↗
PubMed2002

Direct selection of cDNAs from filamentous phage surface display libraries: potential and limitations.

Over the past decade, powerful technologies devoted to survey large molecular libraries for the presence of specific clones using the discriminative power of affinity selection have been developed. Phage surface display technology is the most established of these methods and has revolutionised our ability to select agonistic and antagonistic peptides, antibodies with desired specificity and other drug targets. Thereby ligands are expressed as fusions to phage coat proteins and their respective genes are packaged within the phage. The basic concept of linking the phenotype, expressed as gene product displayed on the phage coat, to its genetic information integrated into the phage genome, creates fusion proteins covalently associated with the infectious particle itself. Binding of the phage to the target molecule offers a selective system by which rare phage carrying the desired gene product can be selected from large phage populations carrying inappropriate sequences. Phage selected in this fashion can be used for subsequent rounds of selection because they are able to self-replicate in suitable host cells, yielding target-specific phage populations after several consecutive rounds of affinity selection. Over 1500 publications describe the use of phage display technology highlighting its performance. Phage display possesses certain limitations, including its use for selection of genes from cDNA libraries that has lagged behind, despite the many accomplishments of this technology. Here we discuss recent progress in construction and screening of cDNA libraries displayed on phage surface and emerging concepts allowing fast identification of virtually all different clones present in enriched libraries.

Bacteriophages↗
PubMedDate not supplied

Circulating biomarkers for lung cancer.

Ideal characteristics of tumor markers and their role in clinical practice are discussed. Measuring markers in screening programs resulted inefficient, while the pathological elevation of one or more markers may be virtually diagnostic of lung cancer in appropriate clinical setting. The elevation of CEA, NSE, TPA and other presented, appears particularly useful in the evaluation of the extent of disease, and may correlate with prognosis, as well as in postsurgical follow-up and monitoring therapy.

Biomarkers, Tumor↗
PubMed1986

Economics of notification and medical screening for high-risk workers.

Measuring the economic impact of notification and intervention programs for workers at high risk of disease from workplace exposure has been virtually nonexistent for several reasons, which will be discussed, and should include a comprehensive view of costs and benefits. A framework for analysis is proposed defining four major clients: the business community, workers and their families, the local and regional public sector, and the federal government. For each client, the positive and negative, quantitative and nonquantitative, direct and indirect, short-run and long-run effects are probed and a summary analysis is made. To illustrate the process, the notification and screening program conducted by the National Institute for Occupational Safety and Health and the Workers' Institute for Safety and Health, Augusta, Georgia, for workers exposed to beta-naphthylamine is described.

Cost-Benefit Analysis↗
PubMed1999

Virtual reality-based training for the diagnosis of prostate cancer.

Prostate malignancies are the second leading cause of cancer deaths among men. The most common method of detecting this disease is digital rectal examination (DRE). Current DRE training is inadequate, since the number of patients that students can practice on is limited. Furthermore, allied care personnel do not train in screening for prostate cancer. Finally, there is no objective way to follow the improvement in DRE skills for medical personnel. This paper presents a virtual reality-based simulator that addresses the above problems. The prototype consists of a PHANToM haptic interface which provides feedback to the trainee's index finger, a motion restricting board, and an SGI workstation, which renders the patient's anatomy. Four types of prostates were modeled--normal, enlarged with no tumor, incipient malignancy (single tumor), and advanced malignancy (tumor cluster). Human factors studies were conducted on both nonmedical students and urology residents in order to quantify the system usefulness. After only five minutes of training, nonmedical students had a 67% correct diagnosis rate of malignant versus nonmalignant cases. This compared with 56% for urology residents in the same trials. Subjective evaluation by the residents pointed out the need to improve the virtual prostate model realism. A control group formed of urology residents performed the same trials on a modified Merck Procar simulator. The control group scored significantly better (96% correct diagnosis of malignancies). We conclude that the virtual prostate palpation simulator, while promising, needs significant improvement in both model realism and haptic interface hardware.

Computer Simulation↗
PubMed2000

Colon polyps and cancer.

Several important studies on screening for colorectal neoplasia were published in 1998-99, including average-risk as well as high-risk groups, and different strategies such as endoscopy, fecal occult blood tests, and other more specific markers of neoplasia. Some of these studies included the use of interventions other than initial screening and polypectomy; a few dealt with diagnostic methods in symptomatic patients, and the new diagnostic tool of virtual colonoscopy was highlighted by several authors. Endoscopic treatment for large adenomas and early colorectal cancer has become more widespread, but clearly it has limitations. Current discussion of the topic of colorectal polyps and cancer is largely based on the concept of the adenoma-carcinoma sequence, which is thought to be the most probable pathogenesis for colorectal cancer.

Adenomatous Polyps↗
PubMed1986

[Results of a pilot study of neonatal screening for congenital biotinidase deficiency].

Biotinidase activity was determined in a pilot study of 78,000 dried blood samples on filter paper. In the assay the liberation of p-aminobenzoic-acid from biotinyl-p-aminobenzoic-acid by biotinidase is tested. One boy was identified to be with biotinidase deficiency. Transient reduction of biotinidase activity to virtually negative test results was observed in 8 preterm babies (recall: 0,01%). Specificity and sensitivity of the test were nearly 100%. We suggest that screening for biotinidase deficiency should be incorporated into existing neonatal screening programs for inborn errors of metabolism. This suggestion is based on the ease of testing, the necessity for presymptomatic laboratory diagnosis, and on the effectiveness of early treatment of the multiple carboxylase deficiency caused by defective biotinidase.

Amidohydrolases↗