Evaluation of digital dermoscopy in a pigmented lesion clinic: Clinician versus computer assessment of malignancy risk
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
2007; 56 (3): 417-421
Correlation between gene expression and morphological alterations in baboon carotid after balloon dilatation injury
2004; 18 (13): 130-?
Digital dermoscopy systems employ computer-based algorithms to quantitate features of pigmented skin lesions (PSLs) and provide an assessment of malignancy risk. We evaluated interobserver concordance of PSL malignancy risk between a pigmented lesion specialist and an artificial neural network (ANN)-based automated digital dermoscopy system. While digital dermoscopy provides a reliable means of image capture, storage, and comparison of PSLs over time, the ANN algorithm requires further training and validation before the malignancy risk assessment feature can be widely used in clinical practice.
View details for DOI 10.1016/j.jaad.2006.08.033
View details for PubMedID 17109995
Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock
2004; 363 (9404): 203-209
Treatment for fibroproliferative restenosis after angioplasty and endovascular surgery is an unmet medical need. Rational therapy and drug design still lack the very basic knowledge about the underlying biological processes leading to pathological changes in the vessel wall. We have developed a primate model for vascular response to denudation-overstretch injury of baboon carotid artery. With this model, we have investigated the time course of vascular expression of 41,000 human cDNA clones and correlated these changes with carotid histology and function. Analysis revealed 20,788 differentially regulated cDNA clones. After high stringency data selection, the most prominently regulated 1629 cDNA clones representing 1510 genes of known function were clustered. Genes corresponding to functional and anatomical alterations in the injured carotid wall were further aligned into functional groups according to Gene Ontology classification. The observed expression patterns faithfully reflected the functional and anatomical alterations observed in the vascular wall in response to injury. The analysis presents a tentative model for genomic response to balloon catheter injury and a road map to identify time-related genomic alterations in human vascular specimens.
View details for DOI 10.1096/fj.04-2225fje
View details for Web of Science ID 000224849900013
Individuality and variation in gene expression patterns in human blood
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2003; 100 (4): 1896-1901
Myocardial failure has a central role in the complex pathophysiology of septic shock and contributes to organ failure and death. During the sepsis-induced inflammatory process, specific factors are released that depress myocardial contractile function. We aimed to identify these mediators of myocardial depression in meningococcal septic shock.We combined gene-expression profiling with protein and cellular methods to identify a serum factor causing cardiac dysfunction in meningococcal septic shock. We identified genes that were significantly upregulated in blood after exposure to meningococci. We then selected for further analysis those genes whose protein products had properties of a myocardial depressant factor--specifically a 12-25 kDa heat-stable protein that is released into serum shortly after onset of meningococcal infection.We identified 174 significantly upregulated genes in meningococcus-infected blood: six encoded proteins that were of the predicted size and had characteristics of a myocardial depressant factor. Of these, interleukin 6 caused significant myocardial depression in vitro. Removal of interleukin 6 from serum samples of patients with meningococcaemia and from supernatants of inflammatory cells stimulated by meningococci in vitro abolished the negative inotropic activity. Furthermore, concentrations in serum of interleukin 6 strongly predicted degree of myocardial dysfunction and severity of disease in children with meningococcal septic shock.Interleukin 6 is a mediator of myocardial depression in meningococcal disease. This cytokine and its downstream mediators could be a target for future treatment strategies.
View details for Web of Science ID 000188243900010
View details for PubMedID 14738793
Effects of biopsy-induced wound healing on residual basal cell and squamous cell carcinomas: rate of tumor regression in excisional specimens
JOURNAL OF CUTANEOUS PATHOLOGY
2003; 30 (2): 139-146
The nature and extent of interindividual and temporal variation in gene expression patterns in specific cells and tissues is an important and relatively unexplored issue in human biology. We surveyed variation in gene expression patterns in peripheral blood from 75 healthy volunteers by using cDNA microarrays. Characterization of the variation in gene expression in healthy tissue is an essential foundation for the recognition and interpretation of the changes in these patterns associated with infections and other diseases, and peripheral blood was selected because it is a uniquely accessible tissue in which to examine this variation in patients or healthy volunteers in a clinical setting. Specific features of interindividual variation in gene expression patterns in peripheral blood could be traced to variation in the relative proportions of specific blood cell subsets; other features were correlated with gender, age, and the time of day at which the sample was taken. An analysis of multiple sequential samples from the same individuals allowed us to discern donor-specific patterns of gene expression. These data help to define human individuality and provide a database with which disease-associated gene expression patterns can be compared.
View details for DOI 10.1073/pnas.252784499
View details for Web of Science ID 000181073000082
View details for PubMedID 12578971
View details for PubMedCentralID PMC149930
Multiple hypothesis testing in microarray experiments
2003; 18 (1): 71-103
Stereotyped and specific gene expression programs in human innate immune responses to bacteria
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2002; 99 (2): 972-977
Wound healing following a partial biopsy of basal cell (BCC) and squamous cell carcinomas (SCC) may induce tumor regression.Nonmelanoma skin cancer (NMSC) biopsy and re-excision specimens from 1994 to 2001 were reviewed for histologic evidence of scar vs. presence of residual tumor in excision specimens. Regressed and non-regressed tumors were analyzed to assess the influence of anatomic location, biopsy technique (punch vs. shave), histologic subtype of BCC or SCC, time interval between biopsy and excision, and patient age.Nine hundred and ten excisions were performed for transected BCC or SCC, 217 (24%) of which showed scar with no residual tumor. Logistic regression analysis revealed significant differences in the regressed vs. non-regressed subsets. SCCs were more likely to regress than BCCs (40% vs. 20%, respectively, p < 0.00001). Independent of the NMSC type, tumors regressed more often following shave rather than punch biopsy (34% vs. 15%, respectively, p < 0.00001), as did tumors on the trunk and extremities compared with head and neck cases (31% vs. 21%, respectively, p < 0.01).In our series, 24% of NMSCs transected on the initial biopsy showed no residual tumor in the excision specimens, implying that some event in the interval between biopsy and excision may lead to the eradication of residual tumor. The exact mechanism is unclear, but wound healing likely plays an important role.
View details for Web of Science ID 000181633300008
View details for PubMedID 12641794
Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling
2000; 403 (6769): 503-511
The innate immune response is crucial for defense against microbial pathogens. To investigate the molecular choreography of this response, we carried out a systematic examination of the gene expression program in human peripheral blood mononuclear cells responding to bacteria and bacterial products. We found a remarkably stereotyped program of gene expression induced by bacterial lipopolysaccharide and diverse killed bacteria. An intricately choreographed expression program devoted to communication between cells was a prominent feature of the response. Other features suggested a molecular program for commitment of antigen-presenting cells to antigens captured in the context of bacterial infection. Despite the striking similarities, there were qualitative and quantitative differences in the responses to different bacteria. Modulation of this host-response program by bacterial virulence mechanisms was an important source of variation in the response to different bacteria.
View details for PubMedID 11805339
Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumours. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of the tumour. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal centre B cells ('germinal centre B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal centre B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumours on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer.
View details for Web of Science ID 000085227300039
View details for PubMedID 10676951