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 1,063 records · Page 59Linked to original sources
PubMedDate not supplied

Visuomotor adaptation in normal aging.

Visuomotor adaptation to a gradual or sudden screen cursor rotation was investigated in healthy young and elderly subjects. Both age groups were equally divided into two subgroups; one subgroup was exposed to 11.25 degrees step increments of visual feedback rotation, every 45 trials (up to a total of 90 degrees), whereas a second subgroup was subjected to 90 degrees rotation from the onset of exposure. Participants performed discrete, horizontal hand movements to virtual targets in four randomized directions. Targets appeared on a computer screen in front of them, and a board prevented vision of the hand at all times. Differential effects of aging on visuomotor adaptation were found, depending on the time course of the visual distortion. In both age groups, early exposure to the sudden visual feedback distortion resulted in typical spiral-like trajectories, which became straighter by late exposure. However, the final adaptation level was reduced in the aged group, although the aftereffects were similar. When subjects were exposed to the gradual distortion, no statistically significant differences in measures of adaptation with advancing age were found. In this case, both age groups appeared to adapt equally. However, after removal of the distortion, elderly subjects showed reduced aftereffects as compared with the young group. These findings suggest differential effects of aging on adaptation to gradual versus sudden visual feedback distortions, and may help to explain the conflicting results obtained in previous visuomotor adaptation studies.

Adaptation, Physiological↗
PubMed1999

Screening blood spots for argininosuccinase deficiency by electrospray tandem mass spectrometry.

Argininosuccinase deficiency is relatively more common in Saudi Arabia than other urea cycle detects (UCD) and its presentation is usually acute and virtually identical to the clinical presentation of other UCD. We developed a rapid, sensitive, and specific screening method for the diagnosis of argininosuccinase deficiency from blood spots. using electrospray tandem mass spectrometry. A 96-well microplate batch process is used for extraction of argininosuccinic acid (ASA), other amino acids and acylcarnitines (Rashed et al. 1995). ASA and other metabolites are derivatized to the corresponding butyl derivatives. The tris-butyl ester of ASA (MH = 459.3) yields two major fragments at m/z 70 and m/z 144 under mild collision induced collision. montitored in the product ion spectrum using a narrow mass range (65-150 kDa). A processing algorithm "CAMPA" is used to automatically calculate the height ratios of selected masses and flags data files as "abnormal" when certain threshold is exceeded. The method is integrated with our existing 2-minute MS/MS method for profiling amino acids and acylcarnitines (Rashed et al. 1997). Using this approach for two years we diagnosed 16 ALD cases from 14 hyperammonemic infants, one high-risk newborn, and one from a regular newborn screening blood spot.

Amino Acid Metabolism, Inborn Errors↗
PubMed1999

Indirect electrochemical detection of type-B trichothecene mycotoxins.

Trichothecene mycotoxins in animal feed and human food can cause fatalities in livestock and disease in humans. In addition, these toxins are suspected chemical warfare agents. Therefore, development of a simple and sensitive method for the screening of trichothecenes is important to prevent economic loss and health hazards. A simple and inexpensive method for the detection of type-B trichothecene mycotoxins has been developed in our laboratory. By hydrolyzing the toxin under basic conditions at 80 degrees C for 1 h it is possible to detect the toxin with simple electrochemical techniques. Deoxynivalenol (DON), commonly known as vomitoxin, was used as a representative compound for type-B trichothecenes in this detection scheme. The detection limit for DON using our procedures was determined to be 9.1 microM in solution, corresponding to 0.24 ppm in a 25-g grain sample if the final extraction volume is 2.2 mL. The linear dynamic detection range was determined to be from 0.32 ppm to greater than 32 ppm. In addition to standard solutions, this method was used on rice samples spiked with DON. It was demonstrated that there is no electrochemical interference from rice extract and that 1 ppm of DON in rice samples can be quantified. This method may be ideal for toxin screening in animal feeds or in runoff from sites that produce the compounds as chemical warfare agents. Since the active moiety in DON is common to virtually all type-B trichothecenes, our approach may be ideal for type-specific screening.

Electrochemistry↗
PubMed2001

Determination of acid alpha-glucosidase activity in blood spots as a diagnostic test for Pompe disease.

BACKGROUND: Pompe disease is an autosomal recessive disorder of glycogen metabolism that is characterized by a deficiency of the lysosomal acid alpha-glucosidase. Enzyme replacement therapy for the infantile and juvenile forms of Pompe disease currently is undergoing clinical trials. Early diagnosis before the onset of irreversible pathology is thought to be critical for maximum efficacy of current and proposed therapies. In the absence of a family history, the presymptomatic detection of these disorders ideally can be achieved through a newborn-screening program. Currently, the clinical diagnosis of Pompe disease is confirmed by the virtual absence, in infantile onset, or a marked reduction, in juvenile and adult onset, of acid alpha-glucosidase activity in muscle biopsies and cultured fibroblasts. These assays are invasive and not suited to large-scale screening. METHODS: A sensitive immune-capture enzyme activity assay for the measurement of acid alpha-glucosidase protein was developed and used to determine the activity of this enzyme in dried-blood spots from newborn and adult controls, Pompe-affected individuals, and obligate heterozygotes. RESULTS: Pompe-affected individuals showed an almost total absence of acid alpha-glucosidase activity in blood spots. The assay showed a sensitivity and specificity of 100% for the identification of Pompe-affected individuals. CONCLUSIONS: The determination of acid alpha-glucosidase activity in dried-blood spots is a useful, noninvasive diagnostic assay for the identification of Pompe disease. With further validation, this procedure could be adapted for use with blood spots collected in newborn-screening programs.

Adult↗
PubMed1993

Should physicians screen for depression in elderly medical inpatients?: Results of a decision analysis.

OBJECTIVE: We wish to determine whether or not elderly medical inpatients should be screened for depressive disorder using either 1) a self-rated depression scale (Geriatric Depression Scale), 2) "usual clinical assessment," or 3) neither, assuming that treatment with tricyclic antidepressants (TCAs) is the primary mode of intervention. METHOD: Based on recent data from epidemiological studies on the prevalence and course of depression, the test characteristics of available screening tests, and the efficacy and side-effects of traditional antidepressants, decision analysis is used to help decide whether or not clinicians should screen for depression in this setting. RESULTS: These calculations indicate that if screening is done solely to identify depressed patients for treatment with TCAs, then the highest utility lies in not screening; however, the difference in utilities between that decision and the decisions to either screen with GDS or screen by usual clinical assessment was only .04 units on a 0 to 100 scale, making the decision virtually a toss-up. Furthermore, even a small variation in one of several clinical factors or test characteristics could give screening a higher utility. In particular, if psychotherapy is considered as the primary intervention, then the utility of screening exceeds that of not screening. CONCLUSION: Characteristics of the screening test, clinical setting, types and safety of available treatments, each impact on the usefulness of screening and must be kept in mind when diagnosing and treating depressed medically ill elders hospitalized in acute care settings.

Aged↗
PubMedDate not supplied

A new strategy for improved secondary screening and lead optimization using high-resolution SPR characterization of compound-target interactions.

Biophysical label-free assays such as those based on SPR are essential tools in generating high-quality data on affinity, kinetic, mechanistic and thermodynamic aspects of interactions between target proteins and potential drug candidates. Here we show examples of the integration of SPR with bioinformatic approaches and mutation studies in the early drug discovery process. We call this combination 'structure-based biophysical analysis'. Binding sites are identified on target proteins using information that is either extracted from three-dimensional structural analysis (X-ray crystallography or NMR), or derived from a pharmacore model based on known binders. The binding site information is used for in silico screening of a large substance library (e.g. available chemical directory), providing virtual hits. The three-dimensional structure is also used for the design of mutants where the binding site has been impaired. The wild-type target and the impaired mutant are then immobilized on different spots of the sensor chip and the interactions of compounds with the wild-type and mutant are compared in order to identify selective binders for the binding site of the target protein. This method can be used as a cost-effective alternative to high-throughput screening methods in cases when detailed binding site information is available. Here, we present three examples of how this technique can be applied to provide invaluable data during different phases of the drug discovery process.

Adenosine Deaminase↗
PubMed1999

Identification of mutations in the repeated part of the autosomal dominant polycystic kidney disease type 1 gene, PKD1, by long-range PCR.

We have used long-range PCR to identify mutations in the duplicated part of the PKD1 gene. By means of a PKD1-specific primer in intron 1, an approximately 13.6-kb PCR product that includes exons 2-15 of the PKD1 gene has been used to search for mutations, by direct sequence analysis. This region contains the majority of the predicted extracellular domains of the PKD1-gene product, polycystin, including the 16 novel PKD domains that have similarity to immunoglobulin-like domains found in many cell-adhesion molecules and cell-surface receptors. Direct sequence analysis of exons encoding all the 16 PKD domains was performed on PCR products from a group of 24 unrelated patients with autosomal dominant polycystic kidney disease (ADPKD [MIM 173900]). Seven novel mutations were found in a screening of 42% of the PKD1-coding region in each patient, representing a 29% detection rate; these mutations included two deletions (one of 3 kb and the other of 28 bp), one single-base insertion, and four nucleotide substitutions (one splice site, one nonsense, and two missense). Five of these mutations would be predicted to cause a prematurely truncated protein. Two coding and 18 silent polymorphisms were also found. When, for the PKD1 gene, this method is coupled with existing mutation-detection methods, virtually the whole of this large, complex gene can now be screened for mutations.

Base Sequence↗
PubMed2005

Construction of a hepatic stellate cells subtracted cDNA library of differentially expressed genes in normal mice and mice with Schistosomiasis japonica.

To construct a hepatic stellate cells (HSCs) subtracted cDNA library to find differentially expressed genes in normal mice and mice infected with Schistosoma japonicum (S. japonicum). Suppression subtractive hybridization (SSH) was used. The cDNA fragments of normal mouse were compared to those of schistosoma-infected mice to find differentially expressed genes. Then differentially expressed cDNA fragments were directly inserted into T/A cloning vector to set up the subtractive library. Amplification of the library was carried out with transformation of DH5alpha. The amplified library contained more than 400 positive bacterial clone, which were then hybridized with forward and backward subtracted probes for differential screening. One hundred positive bacterial clones were randomly selected for sequencing and BLAST analysis. Finally, virtual Northern Blot confirmed such differential expression. The subtracted cDNA library of differentially expressed genes of HSCs was constructed successfully, the library is efficient and lays foundation for screening and cloning new and specific genes of schistosomiasis.

Animals↗
PubMed1999

Computer aids to mental health care.

Computer systems are being used increasingly to aid the assessment and self-treatment of mental health problems in adults. Systems vary hugely in the extent to which they meet all patients' assessment and therapy needs and save clinicians' time. Hardly any single system 1) performs every task required from initial screening to the end of follow-up, 2) works 100% independently of contact with a clinician or technician, and 3) is widely available and supported. Most systems use desk- or laptop computers. Some now use palmtop (hand-held) computers. A few employ computerized phone interviews (interactive voice response), usually from home. Virtual reality as a tool is embryonic. Computer aids save time in screening and outcome-tracking in a wide variety of problems. Computer aids to treatment have had promising outcomes in phobic, anxiety, panic, and obsessive-compulsive disorders, nonsuicidal depression, obesity, and smoking cessation. Some systems are installed in a few places as part of everyday clinical care. A growing number should soon be robust enough to ease the lives of many patients, practitioners, and researchers if use of the systems is carefully integrated into normal clinical practice.

Adult↗
PubMed1986

An automated direct-injection HPLC-method for the electrochemical/fluorimetric quantitation of monoamines and related compounds optimized for the screening of large numbers of animals.

An automated, highly stable HPLC system is described allowing the quantitation of monoamines and related compounds with virtually online data processing and statistical evaluation of the mean values of various differently treated groups of animals. The system is highly suited to the screening of drugs involving large numbers of samples. To ensure long-term, uninterrupted performance, two robust chromatographic systems were developed optimized to separate neighboring peaks as widely as possible. This was achieved by using mobile phases of relatively low pH to retard acidic compounds, and optimal concentrations of the ion-pairing reagent to manipulate the retention times of amines on the RP-18 column, resulting also in clearcut separations from the solvent/tissue peak. Direct injection of deproteinized tissue samples, requiring no clean up procedures is used. One faster system allows measurement of the main biogenic amines, metabolites and TRP, whereas another system allows the simultaneous quantitation of DOPA, 5HTP, NA, MOPEG, NMN, A, MN, VMA, DA, 3MT, DOPAC, HVA, 5HT, 5HIAA and TYR. By pretreatment of animals with a decarboxylase inhibitor the latter system offers the possibility of detecting drug effects in the same animal on either dopamine and serotonin turnover or noradrenaline and serotonin turnover, depending on the brain area chosen. The system described has been running for over a year without major disturbance and with minimal technician attendance.

Animals↗
PubMed2004

Screening for gastric cancer: does it make sense?

Gastric cancer remains the second most frequent and lethal malignancy worldwide, with a wide range of incidence rates in different populations. Reducing its incidence is a priority in many high-risk countries, and screening programmes are often advocated as an option. An effective screening programme should have the following characteristics: (i) the disease should be common in the population, otherwise the individual benefit will not offset the risk, cost and inconvenience of screening of the rest of the population; (ii) the diagnostic test(s) used should be safe, simple, inexpensive and reliable; and (iii) effective treatment should be available. With respect to gastric cancer, these conditions are not fulfilled completely in any population and therefore population-based screening does not appear to be a viable approach to the prevention of this neoplasia. In contrast, gastroscopic screening in selected high-risk subjects would seem appropriate. A more effective strategy, particularly in high-incidence populations, could be the widespread screening and treatment for Helicobacter pylori infection. This could result in the virtually complete elimination of chronic gastritis and its associated conditions, including most peptic ulcers, primary gastric B-cell lymphomas and a major portion of gastric epithelial tumours.

Early Diagnosis↗
PubMedDate not supplied

Developing a mobile pharmacist-conducted wellness clinic for rural Montana communities.

OBJECTIVE: To describe pharmacist-conducted disease screening services in remote communities. SETTING: Frontier, rural, and nonrural counties throughout western Montana. PRACTICE DESCRIPTION: Using federal telehealth funds, a motor home was converted into a mobile office and equipped with a satellite transmitting/receiving dish to provide wireless Internet access. The pharmacist uses an ultrasound unit to test heel bone density, a spirometer to test lung function, and appropriate analyzers to measure A1C and serum lipid levels. Screening clinics are held in conjunction with county health departments, tribal health authorities, community pharmacies, county agricultural extension agents, and Federally Qualified Health Centers. Employee wellness clinics are also conducted. Student pharmacists assist with screenings. PRACTICE INNOVATION: Mobile pharmacist-conducted disease screening clinics in remote communities. MAIN OUTCOME MEASURES: Number of communities served, number of patients screened, percentage of test results out-of-range/patients referred to their primary health care providers for follow-up, number of student pharmacists participating, and total revenues generated. RESULTS: During the first 2 years of the project, IPHARM pharmacists traveled approximately 14,000 miles, conducted 72 clinics in 17 counties and performed 5,100 screening tests for more than 3,100 people. Approximately 36% of all screening test results were outside of expected range. More than 80 student pharmacists, most of whom were on clinical rotations, participated in the clinics and 11 community pharmacists have been trained to conduct screenings. In excess of dollar 70,000 was generated by the project in operating revenue and donations. At the conclusion of IPHARM's first year of operations, the motor home was taken out of service because of the cost of gasoline, difficulties of winter travel with such a large vehicle, and the realization that virtually all host organizations were able to provide space in which the screening clinics could be conducted. CONCLUSION: Pharmacists and student pharmacists are capable of providing disease screening services in remote frontier and rural communities. Obtaining sufficient payment for these services in rural communities to cover costs remains a challenge.

Adult↗
PubMed2005

[Study of the usefulness of large intestine screening inspections using multi-slice CT (MSCT)].

CT-colonography (CT-C), a new diagnostic imaging technique for cancer of the large intestine--which is increasing rapidly owing to westernized eating habits--has advanced from the developmental stage to the stage of practical application, thanks to progress in MSCT and workstation development. Therefore, based on the results of CT-C application using 16 lines of MSCT to a screening test, we reviewed the usefulness of CT-C in our clinic. We supplemented defective depiction, and found that change of position was effective for virtual image exclusion. We consider that CT-C can support diagnosis if the target of screening tests is a polypoid lesion of more than 6 mm. In addition, it is expected that the number of examinations performed during office visits will increase because of the decreased invasiveness of the procedure, its lack of pain, and its ability to provide early lesion detection.

Adolescent↗
PubMed2001

Adaptation of signature-tagged mutagenesis for Toxoplasma gondii: a negative screening strategy to isolate genes that are essential in restrictive growth conditions.

The obligate intracellular parasite Toxoplasma gondii can infect virtually any nucleated cell in any warm-blooded host. Through the effort of many researchers, we are beginning to learn what makes T. gondii such a successful protozoan parasite. A high throughput genetic screen that allows simultaneous examination of a large panel of mutants would greatly facilitate a global investigation of this parasite. Signature-tagged mutagenesis uses a unique DNA sequence to tag an individual mutant so that it can later be identified within a pool. This system allows the efficient identification of parasites carrying mutations in genes that are essential for growth in restrictive but not permissive conditions. We have generated a bank of approximately 4900 signature-tagged T. gondii tachyzoites represented in 89 pools, each of which contains 60 uniquely tagged mutant parasites. We have demonstrated the usefulness of this negative screening strategy with a tissue culture model for pyrimidine salvage using resistance to the pro-drug FUDR. Mutants that are defective for growth in any defined growth condition versus standard tissue culture conditions can now be identified (eg, sensitive to a specific drug, growth in a specialized cell line, or growth within animals).

Animals↗
PubMed1999

Virtual colonography.

Cross-sectional imaging techniques are increasingly being considered as alternative imaging modalities for colorectal screening. While CT-colonography uses air to insufflate the colon, an enema containing small amounts of paramagnetic contrast represents the basis for MR-colonography. Both techniques provide large three-dimensional data sets of the abdomen, containing the entire colon. Using sophisticated post-processing, the colon can be assessed in any desirable plane from various viewpoints. Thus even virtual endoscopic views can be rendered to assess the inside of the colon. This chapter briefly describes the technical aspects underlying both CT- and MR-colonography. Advantages and disadvantages of the two techniques are critically discussed, comparing them with one another as well as with conventional colonoscopy and barium enema.

Colonoscopy↗
PubMed1991

Prenatal screening for chromosome abnormalities using maternal serum chorionic gonadotrophin, alpha-fetoprotein, and age.

Human chorionic gonadotrophin (hCG) levels were assayed retrospectively in stored maternal serum samples from 78 chromosomally abnormal pregnancies and 410 controls matched for gestation and maternal age. The median serum hCG concentration in 49 pregnancies with Down's syndrome was significantly elevated, at 2.18 multiples of the normal median. Significantly reduced hCG concentrations were found in a group of four trisomy 18 pregnancies (all less than 0.4 multiples of the median). Eight cases of unbalanced chromosome rearrangements appeared to show some lowering of hCG levels, while there was no significant difference in the levels in the cases of trisomy 13, balanced translocations, and sex chromosome abnormalities. Maternal serum hCG alone is a better indicator of Down's syndrome pregnancies than maternal age or maternal serum alpha-fetoprotein (AFP), either individually or in combination, and provides a further virtually independent measure of risk. On the basis of our findings, screening for Down's syndrome using hCG and AFP results combined with maternal age risks is predicted to result in a higher detection rate (57 per cent) for a lower false-positive rate (5.0 per cent) than would be attainable by combined AFP and age screening (37 per cent detection at a 6.6 per cent false-positive rate).

Chorionic Gonadotropin↗
PubMed2005

Computer-based training in two-dimensional echocardiography using an echocardiography simulator.

Two-dimensional (2D) echocardiography is a user-dependent technique that poses some inherent problems to the beginner. The first problem for beginners is spatial orientation, especially the orientation of the scan plane in reference to the 3-dimensional (3D) geometry of the heart. The second problem for beginners is steering of the ultrasound probe. We have designed a simulator to teach these skills. On a computer screen a side-by-side presentation of a 3D virtual reality scene on the right side and a 2D echocardiographic view on the left side is given. The virtual scene consists of a 3D heart and an ultrasound probe with scan plane. The 2D echocardiographic image is calculated from 3D echocardiographic data sets that are registered with the heart model to achieve spatial and temporal congruency. The displayed 2D echocardiographic image is defined and controlled by the orientation of the virtual scan plane. To teach hand-eye coordination we equipped a dummy transducer with a 3D tracking system and placed it on a dummy torso. We have evaluated the usability of the simulator in an introductory course for final-year medical students. The simulator was graded realistic and easy to use. According to a subjective self-assessment by a standardized questionnaire the aforementioned skills were imparted effectively.

Adult↗
PubMed1983

Enzyme immunoassay in which a myeloma protein is used for detection of salmonellae.

An enzyme immunoassay (EIA) in which an immunoglobulin A monoclonal antibody from a myeloma (MOPC 467) is used was developed to detect the presence of Salmonella organisms. This myeloma protein binds to a flagellar determinant of the organisms but is not directed toward the H antigens. Of 100 strains tested, 94% were detectable with this antibody. The EIA, used with MOPC 467, is quick, sensitive, and specific, showing virtually no cross-reactivity to other enteric organisms. Initial screening of antibody reactivity was performed by Ouchterlony gel diffusion with the supernatants of heat-treated Salmonella cultures. After this, an EIA was performed on the heat extracts with the myeloma protein, which had been directly coupled to alkaline phosphatase. A positive reaction was indicated by the production of a yellow color after the addition of a substrate (p-nitrophenylphosphate), and this was quantitated by determining the absorbance at 405 nm. The EIA proved to be slightly more sensitive than the Ouchterlony analysis. The sensitivity of the EIA is such that as few as 10(6) Salmonella organisms per ml were detected. This concentration was easily obtained after a 24-h preenrichment incubation of the sample. Mixtures of Salmonella strains with a 10 x concentration of Escherichia coli did not prevent detection of the Salmonella strains. This EIA can be successfully used to detect contamination of foods, as it was used to detect the intentional contamination of infant formula in these studies. Indications are that the EIA is sensitive enough to detect Salmonella strains in M broth subcultures taken directly from a preenrichment culture. Testing of samples could thus be completed 36 h after culture initiation, rather than after 96 h, the time currently needed.

Antibodies, Monoclonal↗