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 1,783 records · Page 99Linked to original sources
PubMed1993

[The genetics of factor XII deficiency].

There are two main forms of factor XII deficiency: patients with immunological cross-reacting material (CRM+) and patients without (CRM-). For 1 case of CRM+ an amino acid substitution (Cys571-->Ser) has been described. We are currently investigating two families of Hageman CRM- trait with the typical hemostaseological pattern: one member with virtually no factor XII activity and antigen, whose sisters and children have about 50% of activity and antigen. To elucidate the genetic defect, primers were synthesized for both exon-intron borders for each of the 14 exons. Polymerase chain reaction (PCR) was performed for each single exon and for any two exons in a row with the intron in between (double-exon screening). We were able to demonstrate that homozygous patients do not have major rearrangements, deletions or insertions of the factor XII gene. To localize the molecular defect, the complete gene was sequenced by cloning the PCR products into pBS. In 1 patient, a single base deletion in exon 12, leading to a nonsense protein, was detected. The propositus was shown to be heterozygous for this defect by a deletion-specific restriction fragment length polymorphism of the PCR product.

Base Sequence↗
PubMed1988

Screening of the Philadelphia variant of galactokinase in racially unmixed black Africans: first results.

In previous reports, it was emphasized that the gene GALKA of galactokinase was the predominant allele in white populations and that another allele, GALKP, which reduces red blood cell activity (RBC GALK), was common in black people. In a group of black Americans living in Philadelphia, the frequency of GALKA was found to be very close to values expected from independent estimation of white admixture. The authors have suggested that the ancestors of these blacks might have been virtually all GALKP homozygous. We have looked for carriers of GALKP genotypes among 73 black Africans; only 33 probands were shown to have a low RBC GALK. To detect white admixture, immunoglobulin allotypes Km and Gm were investigated in 50 individuals of the sample; 15 GALKP carriers with low RBC GALK and 30 of 35 individuals with normal RBC GALK shared Gm phenotypes exclusive to blacks. Our work demonstrates for the first time the polymorphism of GALK in black Africans in the absence of white admixture.

Africa↗
PubMed2002

The fundamental role of epigenetic events in cancer.

Patterns of DNA methylation and chromatin structure are profoundly altered in neoplasia and include genome-wide losses of, and regional gains in, DNA methylation. The recent explosion in our knowledge of how chromatin organization modulates gene transcription has further highlighted the importance of epigenetic mechanisms in the initiation and progression of human cancer. These epigenetic changes -- in particular, aberrant promoter hypermethylation that is associated with inappropriate gene silencing -- affect virtually every step in tumour progression. In this review, we discuss these epigenetic events and the molecular alterations that might cause them and/or underlie altered gene expression in cancer.

Chromosome Mapping↗
PubMed2004

Influence of specimen adequacy on the diagnosis of ASCUS.

The impact of specimen adequacy on the diagnosis of cervical cytology is not fully understood. Virtually, the greatest impact of smear quality limitation factors is on the diagnosis of atypical squamous cells of undetermined significance (ASCUS) because this category is more susceptible to interpretation mistake due to its criteria subjectivity. This study aims to evaluate the impact of smear quality impairing factors on the diagnosis of ASCUS. The 1,507 cases of ASCUS studied were obtained from the Cervical Cancer Screening Program of Paraná (CCSPP). The cases were reviewed by expert cytopathologists and the results were correlated to the specimen adequacy. The results showed that the presence of obscuring blood impairs the correct diagnosis and leads the pathologist to overdiagnose negative smears as ASCUS. The presence of adequate endocervical sampling contributes to a higher rate of correct ASCUS diagnoses but did not influence the pathologist to over- or underestimate the cytological findings.

Cytodiagnosis↗
PubMed2006

Does walking in a virtual environment induce unstable gait? An examination of vertical ground reaction forces.

Virtual reality (VR) can induce postural instability in standing and walking, as quantified with kinematic parameters. This study examines the effect of a VR environment on kinetic gait parameters. Ten healthy volunteers walked on an instrumented treadmill in a VR environment and a non-VR environment. In the VR environment, a corridor with colored vertical stripes comprising the walls was projected onto a concave screen placed in front of the treadmill. The speed of the moving image was perceptually equivalent to the speed of the treadmill, creating an illusion that subjects walked through the corridor. Vertical ground reaction forces were sampled. Kinetic parameters that reflect gait stability (weight acceptance peak force, weight acceptance rate, push-off peak force and push-off rate) were compared between the VR and non-VR environments. Subjects walked in the VR environment with increased magnitudes and rates of weight acceptance force and with increased rates of push-off force. Variability in weight acceptance rates and peak forces, and variability in push-off peak forces, were also increased in the VR environment. The gait deviations reflect a compensatory response to visual stimulation that occurs in the VR environment, suggesting that walking in a VR environment may induce gait instability in healthy subjects.

Adult↗
PubMed1993

Monoclonal antibodies that recognize antigens in human osteosarcoma cells and normal fetal osteoblasts.

Four monoclonal antibodies (HOB-1-4) that react against human osteosarcoma cells (Saos-2) and human fetal osteoblasts in situ were developed by immunizing mice with Saos-2 cells. HOB-1 (IgG1, k) and HOB-2 (IgM, k) stain cytoplasmic antigens in Saos-2 cells, human authentic osteoblasts and occasional cells in liver, spleen and, in the instance of HOB-1, kidney and adrenal gland. On Western blotting of Saos-2 cell lysates, HOB-1 recognizes a single protein species of M(r) 59,000, while HOB-2 reacts with a different species of M(r) 57,000. HOB-3 (IgG1, k) stains a cell membrane associated antigen in Saos-2 cells and osteoblasts in situ. The reaction pattern of this antibody is virtually identical to that seen in alkaline phosphatase (ALP)-positive cells in all organs examined immunohistochemically, except for intestinal epithelium. Both immunoblotting and immunoprecipitation analyses confirm that the antigen detected by HOB-3 is ALP. HOB-4 (IgG1, k) reacts weakly against Saos-2 cells cultured under standard conditions, but strongly following the exposure of the cells to the secretory inhibitor monensin. On frozen section screening, this antibody reacts preferentially with the collagenous extracellular matrix not only of the periosteum but of other tissues and organs as well. The precise identity of the HOB-4 antigen remains to be established. We suggest that these four monoclonal reagents will be useful adjuncts in characterizing the osteoblastic phenotype.

Alkaline Phosphatase↗
PubMed1992

Ambulatory monitoring of sleep-wakefulness patterns in healthy elderly males and females (greater than 88 years): the "Senieur" protocol.

OBJECTIVE: The study was designed to investigate sleep-wake patterns in healthy elderly men and women (greater than 88 years) using ambulatory recording techniques. DESIGN: Cross-sectional observations on 2 consecutive days. METHODS: Two consecutive 24-hour recordings were made. Each 30-second period of the recording was scored as characteristic of wakefulness, REM, and non-REM sleep (stages 1-4). SETTING: Interviews and recordings were done in the home of the elderly, not interfering with the habitual routine. PARTICIPANTS: Among eligible members of the "Senieur" protocol, screened for wellness, seven females (88-102 years) and seven males (88-98 years) volunteered to participate. MAIN OUTCOME MEASURES: Organization of sleep, sleep structure, and daytime mapping. RESULTS: There was no difference between the first and second night recording. Important gender differences were observed: males had significantly less total sleep, shorter REM latency, more transitions to wake from REM, less NREM 3 sleep, and virtually no NREM 4. Daytime napping, REM amount, and distribution did not show sex differences. Although the variability in the amount of napping was considerable, it occupied less than 10 percent of the total sleep time in both women and men. Daytime napping was unrelated to sleep characteristics. CONCLUSIONS: Ambulatory sleep-wake recordings allow an objective and critical evaluation of sleep function in normal aging. Interesting findings include a shift of REM sleep to the first part of the sleep period an increased cycle variability, and non-correlation of night-time sleep with daytime napping. In contrast to earlier findings in elderly persons, a polygraphic and subjective first-night effect was lacking.

Aged↗
PubMed2002

Influence of cues from the anterior medial eyes of virtual prey on Portia fimbriata, an araneophagic jumping spider.

Portia fimbriata from Queensland, Australia, is a jumping spider (Salticidae) that preys on other spiders, including other salticids. Cryptic stalking (palps retracted, walking very slowly and freezing when faced) is a prey-specific tactic deployed exclusively against salticid prey. Using vision alone, P. fimbriata discriminates salticid from non-salticid prey, with the prey salticid's large anterior median (AM) eyes providing critical cues. Here, using computer-rendered virtual three-dimensional lures, we clarify experimentally some of the specific optical cues from AM eyes that influence the behaviour of P. fimbriata. Control lures were based on Jacksonoides queenslandicus, the salticid upon which P. fimbriata most commonly preys in nature. Experimental lures were modified to isolate specific combinations of AM eye features. For presentation to P. fimbriata, lures were projected on a small screen positioned in front of a web-covered platform. Each individual P. fimbriata was tested once with a control lure and once with a lure on which some AM eye feature had been altered. P. fimbriata was affected by the presence-versus-absence of AM eyes, by the size and shape of these eyes and by AM eye position. Horizontal position on the face of a single AM eye had no discernible influence on whether P. fimbriata initiated cryptic stalking, but reduced how often P. fimbriata froze when faced by the prey. The implications of the findings are discussed in relation to perceptual processes underlying the predatory strategy of P. fimbriata.

Animals↗
PubMed2004

The management of fatigue in cancer patients.

Severe, debilitating fatigue is common in cancer patients. For many, it is the symptom that interferes most with normal routines. Virtually every modality used to treat cancer may cause fatigue, as can complications of the disease such as sleep disturbances, infections, malnutrition, hypothyroidism, and anemia. There is a significant overlap between depression and fatigue in many patients. Given the high prevalence of cancer-related fatigue, frequent assessment of patients is essential. The evaluation should include an attempt to identify reversible causes of fatigue, and screening for depression. However, many cancer patients suffer from fatigue even in the absence of any identifiable, reversible cause. For these patients, consideration can be given to suitable exercise programs, educational support and counseling, and energy conservation strategies. A trial of a stimulant medication is also reasonable. Given the heterogeneity of patients, individualized approaches are needed. For anemic patients undergoing chemotherapy, erythropoietic agents can increase hemoglobin levels. The impact of these drugs on fatigue and quality of life is uncertain. Recent reports of increased mortality and thrombotic events in cancer patients treated with epoetin require further investigation.

Antidepressive Agents↗
PubMed1990

Clinical and laboratory features of a severe form of von Willebrand disease in Shetland sheepdogs.

Ten clinically affected Shetland Sheepdogs were evaluated to define their severe bleeding diathesis and were determined to have von Willebrand factor antigen (vWF:Ag) values less than 0.1% by ELISA assay. The virtual absence of vWF protein by ELISA assay and on multimeric analysis was diagnostic of either homozygosity or probable double heterozygosity for the canine von Willebrand disease (vWD) gene. Clinically affected dogs have type-III vWD and are the offspring of 2 heterozygous parents carrying type-I vWD. Twenty-three percent (1,428 dogs) of the more than 6,000 Shetland Sheepdogs screened for vWD at our facility since 1982 tested within the heterozygous carrier range for the common type-I form of this inherited disorder. Veterinarians and breeders should be aware of the potential for bleeding associated with elective and medical procedures in Shetland Sheepdogs and should use caution when breeding carriers of vWD because of the risk of producing clinically affected offspring with severe type-III vWD.

Animals↗
PubMed2001

Phenotyping transgenic embryos: a rapid 3-D screening method based on episcopic fluorescence image capturing.

We describe a technique suitable for routine three-dimensional (3-D) analysis of mouse embryos that is based on episcopic fluorescence images captured during serial sectioning of wax-embedded specimens. We have used this procedure to describe the cardiac phenotype and associated blood vessels of trisomic 16 (Ts16) and Cited2-null mutant mice, as well as the expression pattern of an Myf5 enhancer/beta-galactosidase transgene. The consistency of the images and their precise alignment are ideally suited for 3-D analysis using video animations, virtual resectioning or commercial 3-D reconstruction software packages. Episcopic fluorescence image capturing (EFIC) provides a simple and powerful tool for analyzing embryo and organ morphology in normal and transgenic embryos.

Abnormalities, Multiple↗
PubMed1992

Comparison of the efficacy of digital subtraction and film-screen angiography of the lower limb: prospective study in 50 patients.

We prospectively compared current digital subtraction angiography (DSA) with conventional film-screen angiography (FSA) of the lower limb for evaluation of areas of arterial stenosis and degree of arterial visualization. Fifty patients had both DSA and FSA of a single lower limb. Specific anatomic sites (examiner-selected sites) throughout the lower limb were marked on each film by an experienced angiographer (examiner). These sites consisted of the common femoral, superficial femoral, popliteal, anterior tibial, posterior tibial, peroneal, and dorsalis pedis arteries and bypass grafts, when present. The films were then reviewed blindly by two different experienced angiographers (observers). All sites were graded for the degree of arterial narrowing based on a standard scale (grade 1 = normal, grade 5 = occluded) that also included grading for nonvisualization (grade 6). Each observer also selected the most stenotic site in each anatomic area (observer-selected sites). The data were analyzed for the entire lower limb and at specific anatomic sites. DSA sites were judged to be slightly more narrowed (p less than .05) in the superficial femoral artery by both observers and in the common femoral artery, bypass graft, and overall by a single observer. No other significant differences were found in grade of stenosis or vessel visualization for examiner-selected sites. For observer-selected sites, observers agreed on the location of the most stenotic site 76% of the time for FSA and 69% of the time for DSA. No significant difference was found in grade of stenosis or vessel visualization for either observer for the entire lower limb or at specific anatomic sites. These findings were present when all sites chosen were considered and when there was agreement between sites chosen on FSA and DSA for each observer. In conclusion, optimal-quality FSA and DSA produced virtually equivalent results for angiography of the lower limb for both grade of stenosis/occlusion and vessel visualization.

Angiography↗
PubMed1998

Computerized prescribing: building the electronic infrastructure for better medication usage.

Computerized prescribing in the practice of medicine is a change that is overdue. Virtually all prescriptions in the United States are still handwritten. Instead, medications should be ordered on a computer interacting with 3 databases: patient drug history, scientific drug information and guideline reference, and patient-specific (weight, laboratory) data. Current problems with prescribing on which computerized prescribing could have a positive impact include (1) drug selection; (2) patient role in pharmacotherapy risk-benefit decision making; (3) screening for interactions (drug-drug, drug-laboratory, drug-disease); (4) linkages between laboratory and pharmacy; (5) dosing calculations and scheduling; (6) coordination between team members, particularly concerning patient education; (7) monitoring and documenting adverse effects; and (8) postmarketing surveillance of therapy outcomes. Computerized prescribing is an important component of clinician order entry. Development of this tool has been impeded by a number of conceptual, implementation, and policy barriers. Overcoming these constraints will require clinically and professionally guided vision and leadership.

Clinical Laboratory Information Systems↗
PubMed1999

Psychiatric disorders among survivors of the Oklahoma City bombing.

CONTEXT: Disasters expose unselected populations to traumatic events and can be used to study the mental health effects. The Oklahoma City, Okla, bombing is particularly significant for the study of mental health sequelae of trauma because its extreme magnitude and scope have been predicted to render profound psychiatric effects on survivors. OBJECTIVE: To measure the psychiatric impact of the bombing of the Alfred P. Murrah Federal Building in Oklahoma City on survivors of the direct blast, specifically examining rates of posttraumatic stress disorder (PTSD), diagnostic comorbidity, functional impairment, and predictors of postdisaster psychopathology. DESIGN, SETTING, AND PARTICIPANTS: Of 255 eligible adult survivors selected from a confidential registry, 182 (71%) were assessed systematically by interviews approximately 6 months after the disaster, between August and December 1995. MAIN OUTCOME MEASURES: Diagnosis of 8 psychiatric disorders, demographic data, level of functioning, treatment, exposure to the event, involvement of family and friends, and physical injuries, as ascertained by the Diagnostic Interview Schedule/Disaster Supplement. RESULTS: Forty-five percent of the subjects had a postdisaster psychiatric disorder and 34.3% had PTSD. Predictors included disaster exposure, female sex (for any postdisaster diagnosis, 55% vs 34% for men; chi2 = 8.27; P=.004), and predisaster psychiatric disorder (for PTSD, 45% vs 26% for those without predisaster disorder; chi2 = 6.86; P=.009). Onset of PTSD was swift, with 76% reporting same-day onset. The relatively uncommon avoidance and numbing symptoms virtually dictated the diagnosis of PTSD (94% meeting avoidance and numbing criteria had full PTSD diagnosis) and were further associated with psychiatric comorbidity, functional impairment, and treatment received. Intrusive reexperience and hyperarousal symptoms were nearly universal, but by themselves were generally unassociated with other psychopathology or impairment in functioning. CONCLUSIONS: Our data suggest that a focus on avoidance and numbing symptoms could have provided an effective screening procedure for PTSD and could have identified most psychiatric cases early in the acute postdisaster period. Psychiatric comorbidity further identified those with functional disability and treatment need. The nearly universal yet distressing intrusive reexperience and hyperarousal symptoms in the majority of nonpsychiatrically ill persons may be addressed by nonmedical interventions of reassurance and support.

Adaptation, Psychological↗
PubMed2005

Ecological risk assessment for aquatic species exposed to contaminants in Keelung River, Taiwan.

An ecological risk assessment was conducted for Keelung River in northern Taiwan. The objective of this study was to assess the risk to fish, aquatic insects, and benthic macroinvertebrates associated with chemical-of-potential-concern (COPC) in the river and to rank ecological risk for these chemicals. The protection of at least 95% of the species 90% of the time from acute and chronic COPC exposures was the defined assessment endpoint. Nine inorganic and organic contaminants were selected to evaluate the impact to aquatic community in the Keelung River. The quotient method served as screen level estimation of risk. The Aquatic Ecological Risk Assessment model was used to analyze exposure and ecological effects and to estimate community level risk. The logarithmic regression model between probability and lethal concentration was established. The combined risks of multiple chemicals were evaluated under assumption of additive risk. The results indicated that zinc and copper pose higher risk among metals. Ammonia, copper, and zinc posed virtually all of the risk, while organic COPCs posed a negligible risk. Potential ecological risk from ammonia exposure was greatest. The probability of more than 5% of the species being affected by acute or chronic toxicity of COPCs is about 100%. In average (50% of the time), 99% of the species would be affected by acute toxicity of COPCs, and about all the species would be affected by chronic toxicity of COPCs. Uncertainties in this assessment were associated with variability in ecosystem stressors, exposure data, ecological effect data, and risk characterization.

Ammonia↗
PubMed2006

9-Benzylidene-naphtho[2,3-b]thiophen-4-ones as novel antimicrotubule agents-synthesis, antiproliferative activity, and inhibition of tubulin polymerization.

A novel series of 9-benzylidene-naphtho[2,3-b]thiophen-4-ones and structurally related compounds were synthesized and evaluated for their ability to inhibit tubulin polymerization. The 4-hydroxy-3,5-dimethoxy-benzylidene analogue 15d was identified as a potent cytotoxic agent in an assay based on K562 leukemia cells. Antiproliferative activity of 15d and the 2,4-dimethoxy-3-hydroxy-benzylidene analogue 15e was additionally evaluated against a panel of 12 tumor cell lines, including multidrug resistant phenotypes. All resistant cell lines were sensitive to these compounds. Concentration-dependent flow cytometric studies showed that K562 cells as well as KB/HeLa cells treated by 15d were arrested in the G2/M phases of the cell cycle. Moreover, four compounds strongly inhibited tubulin polymerization with activities higher or comparable to those of the reference compounds. In competition experiments, the most active compounds strongly displaced radiolabeled colchicine from its binding site in the tubulin, showing IC50 values virtually 3- to 4-fold lower than that of colchicine.

Animals↗
PubMedDate not supplied

The recognition of diazinon, an organophosphorus pesticide, when found in samples in the form of decomposition products.

The contents of a bottle, from which a human being was reported to have drunk and which were believed responsible to an organophosphorus poisoning, were submitted for chemical analysis. Initial screening by gas chromatography with phosphorus, sulfur, and nitrogen specific detectors failed to identify any intact organophosphorus pesticide. Mass spectrometric techniques were applied to the identification. Field ionization, field desorption, chemical ionization, exact mass measurements at high resolution, and GC/low resolution mass spectrometry were used to help define the qualitative and partial quantitative nature of the sample components. Results of this study were consistent with the virtually complete conversion of the pesticide, diazinon [Chemical Abstracts reference number 333-41-5], into a mixture of at least twenty-six chemically distinct products or impurities. The most abundant chemical compounds found in the sample included: 2-isopropyl-4-methyl-6-hydroxypyrimidine [2814-20-2]; 2-isopropyl-4-methyl-6-mercaptopyrimidine; 6,6'-dithiobis-(2-isopropyl-4-methylpyrimidine); 6,6'-dithiobis-(2-isopropyl-4-methylpyrimidine); 4-ethoxy-2-isopropyl-6-methylpyrimidine [72799-31-6]; 4-thioethoxy-2-isopropyl-6-methylpyrimidine; triethylphosphorothiolate and triethylphosphorothiolate. Also found were several potent acetylcholinesterase inhibitors: monothionotetraethylpyrophosphate; dithionotetraethylpyrophosphate [3689-24-5]; tetraethylpyrophosphate. Model decomposition studies verified the formation of these compounds. These results were then used to identify compounds in two other samples.

Diazinon↗
PubMed1985

Digital chest radiography: performance evaluation of a prototype unit.

Measurements of the physical performance of a prototype digital chest unit (DCU) are presented. The parameters evaluated were entrance skin exposure, system exposure response and dynamic range, system modulation transfer function (MTF), image noise levels, detective quantum efficiency (DQE) of the detector, and scatter suppression efficiency. Compared with conventional chest imaging systems, the unit has markedly greater exposure latitude, limited spatial resolution, a lower detector DQE, and virtually scatter-free images. Routine clinical exposure levels are comparable with the 1982 national average.

Equipment Design↗