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 1,513 records · Page 84Linked to original sources
PubMed2004

Systematic gene targeting on the X chromosome of Drosophila melanogaster.

The genome of the model organism Drosophila melanogaster has been sequenced and annotated. Based on this groundwork, we performed a systematic genetic screen of the D. melanogaster X chromosome, which carries about one sixth of the genes of the organism. We generated a collection of single P-element insertions to provide genetic and molecular access to virtually all X-chromosomal genes. The study complements earlier work designed to systematically identify vital genes on the X chromosome by targeting transcription units which are phenotypically silent. We describe single UAS sequence-bearing P-element insertions throughout the X chromosome, which allows one to express the tagged genes under control of tissue/organ-directed GAL4 activity. In addition, the present collection of single insertion lines provides a tool to generate chromosomal deletions which are on average less than 33 kb in size.

Animals↗
PubMed2001

Trends in CT colonography.

CT colonography (virtual colonoscopy) is a safe, noninvasive method of examining the large bowel. Since its first description in 1994, the technique has undergone rapid development, stimulating considerable interest in its potential as both a diagnostic and screening tool. Diagnostic performance statistics have been encouraging, with predictive values rivaling those of barium enema and approaching those of endoscopic colonoscopy. Improvements are underway in methods of bowel preparation, scanning procedure, and image display. Increasing experience with the technique is reflected in better understanding and characterization of both two-dimensional and three-dimensional findings, resulting in improved study performance and interpretation. This review attempts to chart the development of CT colonography, with an emphasis on published results and current research interests. We propose potential directions for future study and means toward effective implementation of CT colonography in clinical practice.

Colon↗
PubMed1998

Cloning of a cyclic GMP phosphodiesterase gamma subunit from the ground squirrel retina.

Recent evidence suggests that the two main classes of cones are not only equipped with different photopigments, but also exhibit differences in their downstream phototransduction cascade. An antibody against the gamma subunit of retinal cGMP phosphodiesterase (PDE) had previously been found to label all photoreceptors in the ground squirrel (Spermophilus tridecemlineatus). This property was utilized for the cloning of a cDNA fragment encoding the corresponding polypeptide. A lambda gt11 cDNA library was constructed and screened with the antibody. Positive clones were isolated, subcloned, and sequenced. Clones were used as probes in RNA blot hybridization, and the obtained sequence information was compared to other available gamma-PDE sequences. Four virtually identical cDNA clones were isolated. Both nucleic acid and amino acid sequence alignment placed this gene in the same group as bovine and human cone gamma-phosphodiesterase subunits. The predicted length of the translated protein was 84 amino acids, and its molecular weight 11 kD. The cDNA hybridized with an 0.6-kb transcript in retinal RNA from ground squirrel, Syrian golden hamster, and mouse, and also with a 1.4-kb transcript in the ground squirrel. We conclude that the isolated cDNA fragment encodes a gamma subunit of cone cGMP-PDE. This subunit is expressed in middle-wavelength sensitive cones (the predominant photoreceptor type in this species). It remains to be determined if this subunit is expressed in short-wavelength sensitive cones as well, or if these photoreceptors are equipped with another, unique gamma-PDE subunit.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2001

Barriers to help seeking for mental disorders in a rural impoverished population.

This study examined barriers to seeking mental health care reported by individuals in a rural impoverished population, by screening 646 randomly selected adults for depression, anxiety, and alcohol abuse. Respondents who screened positive were randomly assigned to one of three groups: (1) no intervention, (2) an educational intervention alone, or (3) the educational intervention in the presence of a significant other. Those who screened positive for disorders cited barriers to care at significantly higher rates than respondents who screened negative. Respondents who received the educational intervention endorsed several barriers at significantly lower rates in the follow-up telephone call (subsequent to the intervention) than in the original interview (prior to the intervention). Virtually all respondents in a subsample of 142 subjects (99.3%) said they would seek mental health care if they thought mental health services would help them.

Adult↗
PubMed2006

Retinopathy of prematurity in South Africans at a tertiary hospital: a prospective study.

BACKGROUND AND OBJECTIVES: World Health Organization's vision 20/20 programme has recognized retinopathy of prematurity (ROP) as an important cause of childhood blindness in industrialized and middle-income countries. While ROP is virtually nonexistent in many African countries, ROP is seen in urban areas where facilities for neonatal care exist. The aim of this study is to establish the frequency of ROP in a cohort of patients screened for ROP and to establish if current screening criteria apply to our patients. PATIENTS AND METHODS: Infants with birth weight (BW) of 1500 g or less and/or gestational age of 32 weeks or less were screened for ROP over a 2(1/2)-year period by a single examiner. RESULTS: ROP was observed in 84 of 514 (16.3%) of infants included for analysis. Threshold disease (tROP) was noted in 1.6% of the total cohort although 41/84 babies with ROP were lost prior to regression or progression to tROP. Of the 43/84 adequately followed up, eight (18.6%) developed tROP. An estimated frequency of tROP was more likely to be 2.9%. There was no tROP noted in babies of BW greater than 1250 g. Gestational age was an unreliable risk parameter in our population. CONCLUSION: The projected occurrence rate of tROP is similar to that found in black population in the Multicentre Cryotherapy for ROP Trial. Our data suggest that the screening criterion based on BW can safely be lowered to 1250 g in our population.

Birth Weight↗
PubMed2006

Short interfering RNA (siRNA): tool or therapeutic?

Gene silencing by siRNA (short interfering RNA) is a still developing field in biology and has evolved as a novel post-transcriptional gene silencing strategy with therapeutic potential. With siRNAs, virtually every gene in the human genome contributing to a disease becomes amenable to regulation, thus opening unprecedented opportunities for drug discovery. Besides the well-established role for siRNA as a tool for target screening and validation in vitro, recent progress of siRNA delivery in vivo raised expectations for siRNA drugs as the up-and-coming 'magic bullet'. Whether siRNA compounds will make it as novel chemical entities from 'bench to bedside' will probably depend largely on improving their pharmacokinetics in terms of plasma stability and cellular uptake. Whereas locally administered siRNAs have already entered the first clinical trials, strategies for successful systemic delivery of siRNA are still in a preclinical stage of development. Irrespective of its therapeutic potential, RNAi (RNA interference) has unambiguously become a valuable tool for basic research in biology and thereby it will continue to have a major impact on medical science. In this review, we will give a brief overview about the history and current understanding of RNAi and focus on potential applications, especially as a therapeutic option to treat human disease.

Animals↗
PubMed1998

Medical surveillance for hematological disorders among active and retired oil refinery workers.

Ten-year (1985-1995) results of an expanded medical surveillance program of 2475 active employees and retirees of an oil refinery and petrochemical complex in Illinois are presented. At the end of the program, 116 participants with persistent abnormalities of complete blood cell count had been referred for hematologic evaluation, and most were found to have benign conditions. Fifteen of the 116 were referred for bone marrow and cytogenetic studies. All of the referred active employees (seven) were found to have completely normal bone marrows with no evidence of any myelopathic process. Among the eight retirees, two had normal bone marrows, one was diagnosed with Philadelphia chromosome-positive chronic myelogenous leukemia, one declined to participate, and four were diagnosed to have myelodysplastic syndrome (MDS) of various subtypes. A total of eight cases of MDS were identified, including six cases among program participants and two cases among nonparticipants. The MDS standardized incidence ratio of 1.26 (95% confidence interval = 0.54-2.47) was not statistically significant, and there was virtually no increase of MDS in persons less than 80 years of age (4 observed and 3.8 expected). This MDS increase was entirely from program participants, probably because of intensive follow-up and diagnostic screening. Routine surveillance of complete blood cell count information did not identify any new cases of leukemia or MDS in active employees. These findings suggest that the utility of expanded medical surveillance program in this population is very limited.

Adult↗
PubMed2005

CT colonography: where have we been and where are we going?

Over the past decade, computed tomographic (CT) colonography (also known as virtual colonoscopy) has been used to investigate the colon for colorectal neoplasia. Numerous clinical and technical advances have allowed CT colonography to advance slowly from a research tool to a viable option for colorectal cancer screening. However, substantial controversy remains among radiologists, gastroenterologists, and other clinicians with regard to the current role of CT colonography in clinical practice. On the one hand, all agree there is much excitement about a noninvasive imaging examination that can reliably depict clinically important colorectal lesions. However, this is tempered by results from several recent studies that show the sensitivity of CT colonography may not be as great when performed and the images interpreted by radiologists without expertise and training. The potential to miss important lesions exists; moreover, if polyps cannot be differentiated from folds and residual fecal matter, unnecessary colonoscopy will be performed. In this review, current issues will be discussed regarding colon cancer and the established and reimbursed strategies to screen for it and the past, current, and potential future role of CT colonography.

Colonography, Computed Tomographic↗
PubMed2002

Rational design and development of RDP58.

We used a novel rational design approach in the development of novel immunomodulatory peptides, in particular RDP58, with at least two primary biological activities, inhibition of TNF production and upregulation of heme oxygenase-1 (HO-1) activity. The design strategy used a variety of topological and shape descriptors in combination with an analysis of molecular dynamics trajectories to identify potential drug candidates. The process was initiated using a panel of 19 lead molecules derived from a functionally-important region of HLA I, on the premise that the peptides might modulate immune responses by blocking HLA/T lymphocyte interactions. Each of these 19 peptides was tested in vivo for potential cardiac allograft protection in a mouse model. Outcome of graft survival was the primary data available to describe nine of the peptides as active and ten as inactive. A virtual combinatorial library of 279,936 peptides was then generated, based on physical properties associated with efficacy in the original learning set of 19 peptides--in particular, the distribution of lipophilic residues. The library was screened using descriptors that fell into 2 categories: static (physico-chemical) and dynamic (conformational). The screenings identified 5 peptides with theoretic potential efficacy. These were synthesized and tested for activity in vitro and in vivo. Besides prolonging graft survival in rodents, RDP58 was found to inhibit TNF and increase HO-1 activity; these biological activities were tested exhaustively in various in vivo disease models. RDP58 demonstrated convincing potential to alleviate disease symptoms in many of the experimental diseases.

Animals↗
PubMed1989

SV-40 large-T immortalization of embryonic bone cells: establishment of osteoblastic clonal cell lines.

Cells derived from embryonic rat calvariae were immortalized by retroviral delivery of cDNA for the SV-40 large T antigen and the bacterial neomycin resistance gene. After selection with G418, cells were cloned by limiting dilution and screened for expression of osteoblast characteristics. One clone (RCT-3), derived from cells collected during the third period of enzymatic digestion, showed high constitutive expression of alkaline phosphatase (ALP), synthesized type I collagen in the virtual absence of type III and exhibited a parathyroid hormone (PTH)-responsive adenylate cyclase (EC50, 10 nM). Messenger RNAs for osteonectin and osteopontin were present in RCT-3 cells and osteopontin mRNA was enhanced by 1,25 (OH)2 vitamin D3 treatment. The other cell line (RCT-1), derived from cells released during the first 10 min of digestion, expressed osteoblast features only after 3 d treatment with 1 microM retinoic acid (RA). ALP activity increased from 0.003 to 0.25 mumole/min/mg protein, there was a substantial increase in the steady-state level of type I collagen mRNA and a dose-dependent and saturable response to PTH was induced (EC50, 10 nM). Osteopontin mRNA was induced by 1,25 (OH)2D3. This study has provided two new cell lines which may be useful models for studies of differentiation-related gene expression in bone cells.

Animals↗
PubMed1992

[Prevention of hepatitis B infection in the neonatal care section of the Biella Hospital during a 5-year period from 1986 to 1991. Results and conclusions].

The paper reports the passive and/or active prophylaxis against hepatitis B virus infection carried out in the Neonatal Section of Biella Hospital during the 5-year period 1986-1991. All neonates and non-neonatal subjects at risk of vertical and/or horizontal contagion were vaccinated. The aim of this study was to compare the levels of compliance in relation to serum controls during pregnancy, acceptance of vaccination, percentages of seroconversion and collateral effects. In conclusion, the author underlines the good compliance both during screening in pregnancy and in accepting vaccination. The percentages of seroconversion were similar to those reported in the literature, as was the incidence of HBsAg-positive pregnant women in the local population. Complications were virtually nil both in relation to incidence and severity.

Female↗
PubMed1991

Genetic analysis of functional differences among distinct ferredoxins in Rhodobacter capsulatus.

Rhodobacter capsulatus has been known to possess two ferredoxins (I and II) with distinct physicochemical and structural properties: ferredoxin I is a 2[4Fe-4S] type and the other is a [3Fe-4S] [4Fe-4S] type. To analyze their possible functional differences, their genes (fdxN and fdxA) were cloned, sequenced, and subjected to interposon mutagenesis experiments. The former gene was adjacent to a gene encoding a chloroplast-type [2Fe-2S] ferredoxin (fdxC). Mutants with inactivated fdxN and/or fdxC were obtained, and they showed virtually no growth under nitrogen-fixing conditions. Complementation experiments confirmed that both fdxN and fdxC were required for nitrogen fixation. On the other hand, we have not been able to disrupt fdxA under the screening conditions surveyed, including conditions that do not require nitrogenase activity for growth, suggesting that ferredoxin II could have an unknown essential role(s). These indicate functional differences among multiple ferredoxins in one bacterium other than in cyanobacterial heterocysts and indispensability of certain ferredoxins in nitrogen fixation other than Rhizobium meliloti FdxN.

Amino Acid Sequence↗
PubMed1995

Diagnosis and therapy of hereditary polyposis syndromes.

The hereditary polyposis syndromes include the adenomatous polyposis syndromes (familial adenomatous polyposis and Gardner syndrome, and Turcot syndrome) and the hamartomatous polyposis syndromes (Peutz-Jeghers syndrome, juvenile polyposis, and Cowden's disease). The adenomatous polyposis syndromes are characterized by numerous adenomatous polyps throughout the entire colon and a spectrum of extracolonic manifestations; they invariably progress to colorectal cancer without appropriate intervention. The hamartomatous polyposis syndromes are characterized by diffuse intestinal or colonic hamartomatous polyps, such as juvenile polyps. Although hamartomatous polyps have virtually no malignant potential, the hamartomatous polyposis syndromes are associated with increased risk of cancer, both within and outside the small intestine and the colon. Diagnosis of symptomatic polyposis is by colonoscopy, but in presymptomatic screening of familial adenomatous polyposis, genetic testing can be effective, and it is becoming increasingly available though research laboratories. Management involves treatment of affected individuals, counseling of patients and their families, screening of at-risk individuals, and surveillance of affected patients for extracolonic cancers. Treatment of adenomatous polyposis is primarily colectomy during the second or third decade. For the hamartomatous polyposis syndromes, surveillance for early cancers and their excision remain the only practical, although not totally satisfactory, approaches.

Adenomatous Polyposis Coli↗
PubMed1995

Strategies for viral inactivation.

The risk of transmission of viruses and other pathogenic organisms by blood can be reduced but not eliminated through donor selection and screening methodologies. The safety of blood derivatives prepared from plasma pools from thousands of donors requires virus inactivation, without which transmission rates approach certainty and with which safety can exceed that of single-donor products. Current inactivation methods have reduced and possibly eliminated the transmission of enveloped viruses, eg, hepatitis B and C viruses and HIV; newer methods, when coupled with existing methods, have the likelihood of providing products whose safety matches that of any pharmaceutical product. Success with the virus inactivation of pooled blood products has fostered research into inactivation methods that are compatible with erythrocyte concentrates and platelet concentrates. The most advanced of these employ light-activatable compounds. If successful, virtually all blood products can be free from transmitting viruses and other pathogenic organisms.

Antiviral Agents↗
PubMed2006

[High throughput screening and analysis of prostate cancer-related genes through mining databases].

BACKGROUND & OBJECTIVE: Investigation of differentially expressed genes in prostate cancer tissues may help to understand the molecular mechanism of prostate cancer and provide diagnostic markers or new targets for therapy. The Cancer Genome Anatomy Project (CGAP) public database provides an unprecedented opportunity for cancer researchers to mine genes differentially expressed in cancer tissues by bioinformatic methods. This study was to explore the feasibility of incorporating the Internet-available Serial Analysis of Gene Expression (SAGE) and cDNA databases to find human prostate cancer-related genes. METHODS: SAGE digital gene expression displayer (DGED) and cDNA DGED were used to analyze differentially expressed (>5 folds) genes in malignant prostate tissues compared with normal prostate tissues. The SAGE tags were filtered by their confidence and our 3 criteria. To test the confidence of tags of virtual digital analysis for gene identification, the modified GLGI (generation of longer cDNA fragments from SAGE tags for gene identification) was used to get the cDNA 3' end downstream of 20 tags. Main functions of all candidate genes and their relations to prostate cancer were annotated. RESULTS: Fifty-three differentially expressed genes were screened out by SAGE DGED, 26 of them were up-regulated and 27 were down-regulated in prostate cancer; 28 differentially expressed genes were got by cDNA DGED, 15 of them were up-regulated and 13 were down-regulated in prostate cancer. CONCLUSION: Reasonable use of public databases by the Internet-available tools is a simple, effective approach to get cancer-related genes, and might provide useful clues for further investigation although the results require experimental validation.

DNA, Complementary↗
PubMed2003

Inclusion of HPV testing in routine cervical cancer screening for women above 29 years in Germany: results for 8466 patients.

In a prospective cohort study 8466 women attending routine cervical cancer screening were recruited. Colposcopy was performed on women with any degree of atypia on cytology and/or a positive high-risk human papillomavirus (HPV)-DNA test (HC2; Hybrid Capture 2((c))), and for a randomly selected sample of 3.4% women with negative findings on both. Quality control included reviews of cytology, histology, colposcopy images and retesting of samples with polymerase chain reaction. Test diagnostic performances were based on 7908 women who had complete baseline and follow-up results. Routine histology identified 86 women with high-grade cervical intraepithelial neoplasia (CIN2+), which was confirmed by review histology in only 46 cases. Sensitivity of routine cytology for the detection of CIN2+ was 43.5%, with a specificity, positive predictive value (PPV), negative predictive value (NPV) of 98.0, 11.4 and 99.7%, respectively. Sensitivity of the HC2 test for the detection of CIN2+ was 97.8%, with a specificity, PPV and NPV, of 95.3, 10.9 and 100%, respectively. No high-grade neoplasia was detected in the randomly selected control group. A negative HPV-test result, even in combination with a positive Papanicolaou (Pap) result, virtually excluded any risk of underlying high-grade disease, but this was not the case for a negative Pap result. These data show that HPV testing is of value for the detection or exclusion of prevalent CIN in a routine cervical cancer-screening setting and could be used for further risk classification of women for follow-up management.

Adult↗
PubMed2004

Prevalence and risk factors of hepatitis C infection after cardiac surgery in childhood before and after blood donor screening.

BACKGROUND: Since 1974, the risk of acquiring non-A non-B hepatitis by blood transfusion is well known. In 1999, children having had polytransfusions (group 1) after cardiac surgery prior to the establishment of routine blood donor screening could be identified as a risk group for hepatitis C (HCV) infection. PATIENTS AND METHODS: In 1991, Germany began screening blood donors for hepatitis C. To describe the risk after the implementation of blood donor screening, we studied 211 children (group 2) having had open heart surgery after 1991 and compared prevalence for anti-HCV antibodies and known risk factors to group 1. RESULTS: None of the 211 patients with cardiac surgery after 1991 had detectable anti-HCV antibodies, compared to 67 of the 458 patients (14.6%) of group 1 (p < 0.001). The mean number of operations in both groups was virtually the same (mean 1.7 +/- 0.9 in group 1, mean 1.6 +/- 0.9 in group 2, p = 0.075), whereas the total number of blood products per patient differed significantly (group 1 mean 8 +/- 17.6, group 2 mean 3.5 +/- 2.8; p < 0.001). Multivariate analysis of risk factors demonstrates affiliation to group 1, transfusion of fresh blood, warm whole blood, heparinized blood (p < 0.001) and plasma (p = 0.004) as significant. CONCLUSION: After the implementation of blood donor screening, the risk for HCV infection after cardiac surgery in childhood dropped significantly from 14.6% to < 0.5%. These data show the necessity of HCV screening for patients at risk (operations before 1991) and do not favor a general screening for all patients.

Adolescent↗
PubMed1994

Cystic fibrosis carrier screening in a high-risk population. Participation based on a traditional recruitment process.

OBJECTIVE: Recent advances in molecular genetic (DNA) technology have permitted identification of previously undetectable cystic fibrosis (CF) carriers. Although research has been initiated in the general population, to our knowledge no published studies have looked at the utilization of DNA-based carrier screening in the high-risk CF population (family history of CF). DESIGN: Cross-sectional, diagnostic open trial. SETTING: Carrier testing was offered to a high-risk CF population via adult patients with CF or parents of pediatric patients with CF attending two regional CF clinics over a 3-year period. PARTICIPANTS: Consecutive sample of virtually all patients with CF (n = 118) from a population of 1 million. MAIN RESULTS: Despite free services, written follow-up, and counseling for 99% of patients attending the CF clinic, there was less than 10% participation from high-risk family members (168 blood relatives and 26 spouses of identified carriers or patients with CF; 38 and 156 persons from the adult and pediatric clinic families, respectively). Nevertheless, we identified 91 CF carriers among the 168 high-risk relatives. This is comparable to the number of carriers detected in general population carrier screening that has tested substantially more individuals (> 3000 per study). CONCLUSIONS: Our results suggest that research concerning CF carrier screening not only focus on data about fundamental program resources and numbers of carriers detected but also investigate how information about the availability of carrier screening is disseminated, the motivation behind testing, and the perceived relevance of test results by those tested in the high-risk population. These issues are increasingly relevant as screening becomes feasible using DNA testing for far more prevalent disorders (such as breast cancer and diabetes).

Adolescent↗