Search tips
Search criteria

Results 1-15 (15)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
Document Types
1.  FlyExpress: visual mining of spatiotemporal patterns for genes and publications in Drosophila embryogenesis 
Bioinformatics  2011;27(23):3319-3320.
Summary: Images containing spatial expression patterns illuminate the roles of different genes during embryogenesis. In order to generate initial clues to regulatory interactions, biologists frequently need to know the set of genes expressed at the same time at specific locations in a developing embryo, as well as related research publications. However, text-based mining of image annotations and research articles cannot produce all relevant results, because the primary data are images that exist as graphical objects. We have developed a unique knowledge base (FlyExpress) to facilitate visual mining of images from Drosophila melanogaster embryogenesis. By clicking on specific locations in pictures of fly embryos from different stages of development and different visual projections, users can produce a list of genes and publications instantly. In FlyExpress, each queryable embryo picture is a heat-map that captures the expression patterns of more than 4500 genes and more than 2600 published articles. In addition, one can view spatial patterns for particular genes over time as well as find other genes with similar expression patterns at a given developmental stage. Therefore, FlyExpress is a unique tool for mining spatiotemporal expression patterns in a format readily accessible to the scientific community.
PMCID: PMC3223365  PMID: 21994220
2.  The Protein Information and Property Explorer 2: Gaggle-like exploration of biological proteomic data within one webpage 
Proteomics  2010;11(1):154-158.
The Protein Information and Property Explorer 2 (PIPE2) is an enhanced software program and updated web application that aims at providing the proteomic researcher a simple, intuitive user interface through which to begin inquiry into the biological significance of a list of proteins typically produced by MS/MS proteomic processing software. PIPE2 includes an improved interface, new data visualization options, and new data analysis methods for combining disparate, but related, data sets. In particular, PIPE2 has been enhanced to handle multi-dimensional data like protein abundance, gene expression, and/or interaction data. The current architecture of PIPE2, modeled after that of the Gaggle (a programming infrastructure for interoperability between separately developed software tools), contains independent functional units that can be instantiated and pieced together at the user’s discretion to form a pipelined analysis workflow. Among these functional units is the Network Viewer component, which adds rich network analysis capabilities to the suite of existing proteomic web resources. Additionally, PIPE2 implements a framework within which new analysis procedures can be easily deployed and distributed over the World Wide Web. PIPE2 is available as a web service at
PMCID: PMC3072271  PMID: 21182202
Interaction networks; Biological inference; Gene ontology; Software analysis
3.  Systemic chimerism in human female recipients of male livers 
Lancet  1992;340(8824):876-877.
We have previously reported data from clinical and laboratory animal observations which suggest that organ tolerance after transplantation depends on a state of balanced lymphodendritic cell chimerism between the host and donor graft. We have sought further evidence to support this hypothesis by investigating HLA-mismatched liver allograft recipients.
9 of 9 female recipients of livers from male donors had chimerism in their allografts and extrahepatic tissues, according to in-situ hybridisation and molecular techniques 10 to 19 years post-transplantation. In 8 women with good graft function, evidence of the Y chromosome was found in the blood (6/8), skin (8/8), and lymph nodes (7/8). A ninth patient whose transplant failed after 12 years from recurrent chronic viral hepatitis had chimerism in her lymph nodes, skin, jejunum, and aorta at the time of retransplantation.
Although cell migration is thought to take place after all types of transplantation, the large population of migratory cells in, and the extent of their seeding from, hepatic grafts may explain the privileged tolerogenicity of the liver compared with other organs.
PMCID: PMC3184834  PMID: 1357298
4.  ATAQS: A computational software tool for high throughput transition optimization and validation for selected reaction monitoring mass spectrometry 
BMC Bioinformatics  2011;12:78.
Since its inception, proteomics has essentially operated in a discovery mode with the goal of identifying and quantifying the maximal number of proteins in a sample. Increasingly, proteomic measurements are also supporting hypothesis-driven studies, in which a predetermined set of proteins is consistently detected and quantified in multiple samples. Selected reaction monitoring (SRM) is a targeted mass spectrometric technique that supports the detection and quantification of specific proteins in complex samples at high sensitivity and reproducibility. Here, we describe ATAQS, an integrated software platform that supports all stages of targeted, SRM-based proteomics experiments including target selection, transition optimization and post acquisition data analysis. This software will significantly facilitate the use of targeted proteomic techniques and contribute to the generation of highly sensitive, reproducible and complete datasets that are particularly critical for the discovery and validation of targets in hypothesis-driven studies in systems biology.
We introduce a new open source software pipeline, ATAQS (Automated and Targeted Analysis with Quantitative SRM), which consists of a number of modules that collectively support the SRM assay development workflow for targeted proteomic experiments (project management and generation of protein, peptide and transitions and the validation of peptide detection by SRM). ATAQS provides a flexible pipeline for end-users by allowing the workflow to start or end at any point of the pipeline, and for computational biologists, by enabling the easy extension of java algorithm classes for their own algorithm plug-in or connection via an external web site.
This integrated system supports all steps in a SRM-based experiment and provides a user-friendly GUI that can be run by any operating system that allows the installation of the Mozilla Firefox web browser.
Targeted proteomics via SRM is a powerful new technique that enables the reproducible and accurate identification and quantification of sets of proteins of interest. ATAQS is the first open-source software that supports all steps of the targeted proteomics workflow. ATAQS also provides software API (Application Program Interface) documentation that enables the addition of new algorithms to each of the workflow steps. The software, installation guide and sample dataset can be found in
PMCID: PMC3213215  PMID: 21414234
6.  Liver Transplantation Without the Use of Blood Products 
To examine the techniques and the outcome of liver transplantation with maximal conservation of blood products and to analyze the potential benefits or drawbacks of blood conservation and salvage techniques.
Case series survey.
Tertiary care, major university teaching hospital.
Patients and Methods
Four patients with religious objections to blood transfusions who were selected on the basis of restrictive criteria that would lower their risk for fatal hemorrhage, including coagulopathy, a thrombosed splanchnic venous system requiring extensive reconstruction, active bleeding, and associated medical complications. All patients were pretreated with erythropoietin to increase production of red blood cells. All operations were performed at the same institution, with a 36-month follow-up.
Orthotopic liver transplantation that used blood salvage, plateletpheresis, and autotransfusion and the withholding of the use of human blood products with the exception of albumin.
Main Outcome Measures
Survival and postoperative complications, with the effectiveness of erythropoietin and plateletpheresis as secondary measures.
All patients are alive at 36 months after orthotopic liver transplantation. One patient, a minor (13 years of age), was transfused per a state court ruling. Erythropoietin increased the production of red blood cells as shown by a mean increase in hematocrit levels of 0.08. Plateletpheresis allowed autologous, platelet-rich plasma to be available for use after allograft reperfusion. Three major complications were resolved or corrected without sequelae. Only one patient developed postoperative hemorrhage, which was corrected surgically. The mean charge for bloodless surgery was $174 000 for the three patients with United Network for Organ Sharing (UNOS) status 3 priority for transplantation. This result was statistically significant when these patients were compared with all the patients with UNOS status 3 priority during the same period who met the same restrictive guidelines (P<.05). Only 19 of 1009 orthotopic liver transplantations performed at our institution were similiar according to the UNOS status and the fulfillment of the guidelines. The mean charge for these comparison patients was $327 000, 3.8% of which was related to transfusions.
Orthotopic liver transplantation without the use of blood products is possible. Blood conservation techniques do not increase morbidity or mortality and can result in fewer transfusion-related, in-hospital charges.
PMCID: PMC3022432  PMID: 8185476
Transplantation  1995;59(2):212-217.
Seventy-two long-surviving liver transplant recipients were evaluated prospectively, including a baseline allograft biopsy for weaning off of immunosuppression. Thirteen were removed from candidacy because of chronic rejection (n=4), hepatitis (n=2), patient anxiety (n=5), or lack of cooperation by the local physician (n=2). The other 59, aged 12–68 years, had stepwise drug weaning with weekly or biweekly monitoring of liver function tests. Their original diagnoses were PBC (n=9), HCC (n=1), Wilson’s disease (n=4), hepatitides (n=15), Laennec’s cirrhosis (n=1), biliary atresia (n=16), cystic fibrosis (n=1), hemochromatosis (n=1), hepatic trauma (n=1), alpha-1-antitrypsin deficiency (n=9), and secondary biliary cirrhosis (n=1). Most of the patients had complications of long-term immunosuppression, of which the most significant were renal dysfunction (n=8), squamous cell carcinoma (n=2) or verruca vulgaris of skin (n=9), osteoporosis and/or arthritis (n=12), obesity (n=3), hypertension (n=11), and opportunistic infections (n=2). When azathioprine was a third drug, it was stopped first. Otherwise, weaning began with prednisone, using the results of corticotropin stimulation testing as a guide. If adrenal insufficiency was diagnosed, patients reduced to <5 mg/day prednisone were considered off of steroids. The baseline agents (azathioprine, cyclosporine, or FK506) were then gradually reduced in monthly decrements. Complete weaning was accomplished in 16 patients (27.1%) with 3–19 months drug-free follow-up, is progressing in 28 (47.4%), and failed in 15 (25.4%) without graft losses or demonstrable loss of graft function from the rejections. This and our previous experience with self-weaned and other patients off of immunosuppression indicate that a significant percentage of appropriately selected long-surviving liver recipients can unknowingly achieve drug-free graft acceptance. Such attempts should not be contemplated until 5–10 years posttransplantation and then only with careful case selection, close monitoring, and prompt reinstitution of immunosuppression when necessary.
PMCID: PMC3005337  PMID: 7839442
8.  Cell Migration and Chimerism After Whole-organ Transplantation: The Basis of Graft Acceptance 
Hepatology (Baltimore, Md.)  1993;17(6):1127-1152.
Improvements in the prevention or control of rejection of the kidney and liver have been largely interchangeable (1, 2) and then applicable, with very little modification, to thoracic and other organs. However, the mechanism by which anti rejection treatment permits any of these grafts to be “accepted” has been an immunological enigma (3, 4). We have proposed recently that the exchange of migratory leukocytes between the transplant and the recipient with consequent long-term cellular chimerism in both is the basis for acceptance of all whole-organ allografts and xenografts (5). Although such chimerism was demonstrated only a few months ago, the observations have increased our insight into transplantation immunology and have encouraged the development of alternative therapeutic strategies (6).
PMCID: PMC2964270  PMID: 8514264
9.  Early Tolerance in Pediatric Liver Allograft Recipients 
Journal of pediatric surgery  1994;29(6):754-756.
The authors report on six pediatric liver transplant recipients for whom allograft tolerance occurred shortly after transplantation (ie, less than 1.5 years). All the patients had associated life-threatening viral complications. They are currently immunocompetent. The tolerant state may be related to the development of a TH2 cytokine pattern.
PMCID: PMC2963428  PMID: 8078013
Liver transplantation; allograft
10.  Combined liver–kidney transplantation and the effect of preformed lymphocytotoxic antibodies 
Transplant immunology  1994;2(1):61-67.
Thirty-eight sequentially placed liver and kidney allografts were evaluated with respect to patient and graft survival, and the influence of preformed lymphocytotoxic antibodies was analysed. The results suggest that the survival rate of combined liver and kidney transplantation is similar to the survival rate of liver transplantation alone. Sequentially placed kidney allografts may be protected from hyperacute rejection in the presence of donor specific lymphocytotoxic antibodies, but not in all instances. Both patient and kidney allograft survival was lower in positive crossmatch patients (33% and 17% respectively) than in negative crossmatch patients (78% and 75%). High levels of panel reactive antibodies (>10%) also appeared to have a deleterious effect on survival, although the majority of the patients who failed also had a positive crossmatch. Although preformed lymphocytotoxic antibodies are not an absolute contraindication to combined liver–kidney transplantation, they do appear to have a deleterious effect on long-term graft survival. However, more correlation with clinical parameters is needed.
PMCID: PMC2956073  PMID: 8081794
Transplantation  1993;55(6):1272-1277.
Chimerism was demonstrated with immunocytochemical and/or polymerase chain reaction techniques in kidney allografts and in the native skin, lymph nodes, or blood of 5 of 5 patients who received continuously functioning renal transplants from 1 or 2 haplotype HLA mismatched consanguineous donors (4 parents, 1 aunt) 27–29 years ago. In the 4 cases where the kidney donor still was alive to provide stimulator lymphocytes for testing, these provoked no (n=2) or modest (n=2) MLR in contrast to vigorous MLR to third party lymphocytes. In all 4 cases, the donor cells failed to generate in vitro cytotoxic effector cells (cell-mediated lymphocytotoxicity). These findings are in accord with the hypothesis that cell migration, repopulation, and chimerism are seminal events that define graft acceptance and ultimately can lead to acquired donor-specific nonresponsiveness (tolerance).
PMCID: PMC2953386  PMID: 8516813
12.  Allografts Surviving for 26 to 29 Years Following Living-Related Kidney Transplantation: Analysis by Light Microscopy, In Situ Hybridization for the Y Chromosome, and Anti-HLA Antibodies 
We studied seven patients aged 14 to 40 years who received living-related kidney transplants and had allograft survivals of 26 to 29 years. The blood urea and creatinine were either within normal limits or marginally elevated. Histopathologic examination showed only mild mesangial expansion, interstitial fibrosis, and arteriosclerosis. Immunoperoxidase staining with anti-HLA antibodies or in situ hybridization with a Y chromosome probe showed persistence of donor tubular epithelium and vascular endothelium within the graft. Recipient-derived glomerular cells were seen in one case, and interstitial lymphocytic infiltrates were seen in all cases. A review of the clinicopathologic data available for these cases indicated that both central and peripheral immunologic mechanisms contributed to the maintenance of prolonged graft survival. This extended survival was independent of six antigen matching, down-regulation of donor HLA antigen expression, and ingrowth of host epithelium/endothelium into the allograft.
PMCID: PMC2950638  PMID: 8023827
Kidney; transplantation; donor; recipient; Y chromosome
13.  Effectiveness of rotavirus vaccination against childhood diarrhoea in El Salvador: case-control study 
Objective To evaluate the effectiveness of a monovalent rotavirus vaccine against severe rotavirus disease and to assess its impact on diarrhoea in children aged less than 2 years after national introduction in El Salvador, a low-middle income country in Central America.
Design Matched case-control study.
Setting Seven hospitals in cities across El Salvador, January 2007 to June 2009.
Participants 323 children aged less than 2 years admitted with laboratory confirmed rotavirus diarrhoea and 969 healthy controls matched for age and neighbourhood.
Main outcome measure Effectiveness of rotavirus vaccination ((1–adjusted odds ratio of vaccination)×100) against rotavirus diarrhoea requiring hospital admission.
Results Cases and controls were similar for breast feeding, premature birth, maternal education, and socioeconomic variables. G1P[8] strains were identified in 92% of rotavirus cases. Effectiveness of two doses of vaccination against diarrhoea requiring hospital admission was 76% (95% confidence interval 64% to 84%). Protection was significantly lower (P=0.046) among children aged 12 months or more (59%, 27% to 77%) compared with children aged 6-11 months (83%, 68% to 91%). One dose of vaccine was 51% (26% to 67%) effective. At the sentinel hospitals, all admissions for diarrhoea among children under 5 declined by 40% in 2008 and by 51% in 2009 from the prevaccine year 2006.
Conclusions A monovalent rotavirus vaccine was highly effective against admissions for rotavirus diarrhoea in children aged less than 2 years in El Salvador and substantially reduced the number of such admissions in this low-middle income setting. The impact on disease epidemiology after vaccination, particularly among older children, warrants future attention.
PMCID: PMC2886195  PMID: 20551120
14.  The Complete Genome Sequence of Roseobacter denitrificans Reveals a Mixotrophic Rather than Photosynthetic Metabolism▿ †  
Journal of Bacteriology  2006;189(3):683-690.
Purple aerobic anoxygenic phototrophs (AAPs) are the only organisms known to capture light energy to enhance growth only in the presence of oxygen but do not produce oxygen. The highly adaptive AAPs compose more than 10% of the microbial community in some euphotic upper ocean waters and are potentially major contributors to the fixation of the greenhouse gas CO2. We present the complete genomic sequence and feature analysis of the AAP Roseobacter denitrificans, which reveal clues to its physiology. The genome lacks genes that code for known photosynthetic carbon fixation pathways, and most notably missing are genes for the Calvin cycle enzymes ribulose bisphosphate carboxylase (RuBisCO) and phosphoribulokinase. Phylogenetic evidence implies that this absence could be due to a gene loss from a RuBisCO-containing α-proteobacterial ancestor. We describe the potential importance of mixotrophic rather than autotrophic CO2 fixation pathways in these organisms and suggest that these pathways function to fix CO2 for the formation of cellular components but do not permit autotrophic growth. While some genes that code for the redox-dependent regulation of photosynthetic machinery are present, many light sensors and transcriptional regulatory motifs found in purple photosynthetic bacteria are absent.
PMCID: PMC1797316  PMID: 17098896
15.  Pink urine and a petechial rash 
Western Journal of Medicine  2002;176(3):155-156.
PMCID: PMC1071702  PMID: 12038467

Results 1-15 (15)