Erratum to "Primary Desmoplastic Melanoma of the Penis".

[This corrects the article DOI: 10.1155/2015/706572.].

Primary Desmoplastic Melanoma of the Penis.

Desmoplastic melanomas are rare amelanotic melanomas that usually occur on skin with sun exposure. In this report, we present a 72-year-old man who presented with a desmoplastic melanoma of the penis. To our knowledge this represents the first reported case of primary desmoplastic melanoma of the penis. We discuss the pathologic differential and histologic evaluation.

Pediatric renal solitary fibrous tumor: report of a rare case and review of the literature.

Solitary fibrous tumors (SFTs) are unusual spindle cell neoplasms initially described in the pleura but have since been discovered in many extrapleural locations. SFT of the kidney is extremely rare, the majority occurring in middle-aged adults. To date, only two pediatric cases of renal SFT have been reported. We report a case of large SFT in the kidney of a 3-year-old boy that was clinically and radiologically thought to be a nephroblastoma. This case is the first pediatric renal SFT to be reported with detailed histopathologic and cytogenetic analyses. SFT should be included in the differential diagnosis of pediatric renal tumors.

Thyroid-like follicular carcinoma of the kidney in a young patient with history of pediatric acute lymphoblastic leukemia.

Thyroid-like follicular carcinoma of the kidney (TLFCK) is a rare histological variant of renal cell carcinoma not currently included in the World Health Organization classification of renal tumors. Only 24 previous cases of TLFCK have been reported to date. We report a case of TLFCK in a 19-year-old woman with history of pediatric acute lymphoblastic leukemia. This patient is the youngest with TLFCK to be reported to date and the first with history of lymphoblastic leukemia. The development of TLFCK in a young patient with history of lymphoblastic leukemia is interesting and suggests that genes involved in leukemogenesis may also be important for TLFCK pathogenesis. Recognition of TLFCK is important to distinguish it from other conditions that show thyroid-like features, as a misdiagnosis can result in adverse patient care.

Incidental pulmonary nodules detected on abdominal computed tomography.

OBJECTIVES: To review the characteristics and outcome of incidental pulmonary nodules reported on abdominal computed tomography (CT). METHODS: A database search of abdominal CTs from January 1, 2004, to December 31, 2006, revealed 413 patients with incidental pulmonary nodules and at least one follow-up chest CT. Demographic information, nodule characteristics, and eventual outcome of the nodules were analyzed. RESULTS: Of the 413 patients, 56% had benign nodules, 11% had malignant nodules, and the remaining 33% had insufficient follow-up. There was a statistically significant difference (P < 0.05) in the age of the patients, history of malignancy, and size of the incidental nodule between benign and malignant groups. No malignant nodules were found in patients younger than 59 years who did not have a known or suspected malignancy. CONCLUSION: Small pulmonary nodules (<8 mm) on abdominal CT in patients younger than 50 years with no history of malignancy are unlikely to be malignant.

Analysis of glycoprotein E-selectin ligands on human and mouse marrow cells enriched for hematopoietic stem/progenitor cells.

Although well recognized that expression of E-selectin on marrow microvessels mediates osteotropism of hematopoietic stem/progenitor cells (HSPCs), our knowledge regarding the cognate E-selectin ligand(s) on HSPCs is incomplete. Flow cytometry using E-selectin-Ig chimera (E-Ig) shows that human marrow cells enriched for HSPCs (CD34(+) cells) display greater E-selectin binding than those obtained from mouse (lin(-)/Sca-1(+)/c-kit(+) [LSK] cells). To define the relevant glycoprotein E-selectin ligands, lysates from human CD34(+) and KG1a cells and from mouse LSK cells were immunoprecipitated using E-Ig and resolved by Western blot using E-Ig. In both human and mouse cells, E-selectin ligand reactivity was observed at ~ 120- to 130-kDa region, which contained two E-selectin ligands, the P-selectin glycoprotein ligand-1 glycoform "CLA," and CD43. Human, but not mouse, cells displayed a prominent ~ 100-kDa band, exclusively comprising the CD44 glycoform "HCELL." E-Ig reactivity was most prominent on CLA in mouse cells and on HCELL in human cells. To further assess HCELL's contribution to E-selectin adherence, complementary studies were performed to silence (via CD44 siRNA) or enforce its expression (via exoglycosylation). Under physiologic shear conditions, CD44/HCELL-silenced human cells showed striking decreases (> 50%) in E-selectin binding. Conversely, enforced HCELL expression of LSK cells profoundly increased E-selectin adherence, yielding > 3-fold more marrow homing in vivo. These data define the key glycoprotein E-selectin ligands of human and mouse HSPCs, unveiling critical species-intrinsic differences in both the identity and activity of these structures.

Identification of documented medication non-adherence in physician notes.

Medication non-adherence is common and the physicians awareness of it may be an important factor in clinical decision making. Few sources of data on physician awareness of medication non-adherence are available. We have designed an algorithm to identify documentation of medication non-adherence in the text of physician notes. The algorithm recognizes eight semantic classes of documentation of medication non-adherence. We evaluated the algorithm against manual ratings of 200 randomly selected notes of hypertensive patients. The algorithm detected 89% of the notes with documented medication non-adherence with specificity of 84.7% and positive predictive value of 80.2%. In a larger dataset of 1,000 documents, notes that documented medication non-adherence were more likely to report significantly elevated systolic (15.3% vs. 9.0%; p = 0.002) and diastolic (4.1% vs. 1.9%; p = 0.03) blood pressure. This novel clinically validated tool expands the range of information on medication non-adherence available to researchers.

Identification of inactive medications in narrative medical text.

Discontinued medications are frequently not removed from EMR medication lists - a patient safety risk. We developed an algorithm to identify inactive medications using in the text of narrative notes in the EMR. The algorithm was evaluated against manual review of 297 randomly selected notes. One in five notes documented inactive medications. Sensitivity and precision of 87.7% and 80.7%, respectively, on per-note basis and 66.3% and 80.0%, respectively, on per-medication basis. When medication names missing from the dictionary were excluded, the algorithm achieved sensitivity of 91.4%. Using real clinical data, the algorithm identified inactive medications documented in the note but still listed as active on the patients medication list in more than one in ten notes. Documentation of inactive medications is common in narrative provider notes and can be computationally extracted. This technology could be employed in real-time patient care as well as for research and quality of care monitoring.

Identification of misspelled words without a comprehensive dictionary using prevalence analysis.

Misspellings are common in medical documents and can be an obstacle to information retrieval. We evaluated an algorithm to identify misspelled words through analysis of their prevalence in a representative body of text. We evaluated the algorithm's accuracy of identifying misspellings of 200 anti-hypertensive medication names on 2,000 potentially misspelled words randomly selected from narrative medical documents. Prevalence ratios (the frequency of the potentially misspelled word divided by the frequency of the non-misspelled word) in physician notes were computed by the software for each of the words. The software results were compared to the manual assessment by an independent reviewer. Area under the ROC curve for identification of misspelled words was 0.96. Sensitivity, specificity, and positive predictive value were 99.25%, 89.72% and 82.9% for the prevalence ratio threshold (0.32768) with the highest F-measure (0.903). Prevalence analysis can be used to identify and correct misspellings with high accuracy.

Identification of inactive medications in narrative physician notes.

Information about inactive medications is important for patient safety but is frequently missing from the electronic medical record. We investigated the feasibility of extracting this information from narrative physician notes. Our analysis of 298 physician notes showed that 1 in 3 notes contains documentation of medication discontinuation. This documentation can be described by one of six semantic fields. Documentation of inactive medications is common in narrative documents and could potentially be extracted using semantic analysis.

HCELL is the major E- and L-selectin ligand expressed on LS174T colon carcinoma cells.

Engagement of vascular E-selectin and leukocyte L-selectin with relevant counter-receptors expressed on tumor cells contributes to the hematogenous spread of colon carcinoma. We recently demonstrated that the LS174T colon carcinoma cell line expresses the CD44 glycoform known as hematopoietic cell E-/L-selectin ligand (HCELL), which functions as a high affinity E- and L-selectin ligand on these cells. To define the contribution of HCELL to selectin-mediated adhesion on intact tumor cells, we measured the binding of LS174T cells transduced with CD44 short interfering RNA (siRNA) or with vector alone to 6-h interleukin-1beta-stimulated human umbilical vein endothelial cells (HUVEC) and to human peripheral blood mononuclear cells (PBMC) under physiological flow conditions. LS174T cell attachment to HUVEC was entirely E-selectin-dependent, and PBMC tethering to tumor cell monolayers was completely L-selectin-dependent. At physiological shear stress, CD44 siRNA transduction led to an approximately 50% decrease in the number of LS174T cells binding to stimulated HUVEC relative to vector alone-transduced cells. CD44 siRNA-transduced cells also rolled significantly faster than vector-transduced cells on HUVEC, indicating prominent HCELL participation in stabilizing tumor cell-endothelial adhesive interactions against fluid shear. Furthermore, HCELL was identified as the principal L-selectin ligand on LS174T cells, as PBMC binding to CD44 siRNA-transduced tumor cells was reduced approximately 80% relative to vector-transduced cells. These data indicate that expression of HCELL confers robust and predominant tumor cell binding to E- and L-selectin, highlighting a central role for HCELL in promoting shear-resistant adhesive interactions essential for hematogenous cancer dissemination.

Identification of cis sequences required for lytic DNA replication and packaging of murine gammaherpesvirus 68.

Human gammaherpesviruses are associated with lymphomas and other malignancies. Murine gammaherpesvirus 68 (MHV-68) infection of mice has emerged as a model for understanding gammaherpesvirus pathogenesis in vivo. In contrast to human gammaherpesviruses, MHV-68 replicates in permissive cell lines in a robust manner, presenting an efficient model to study the basic mechanisms for DNA replication and recombination processes. In addition, MHV-68 also infects a broad range of cells of different tissue types and from different host species, and the viral genome persists as an episome in infected cells. These features make MHV-68 an attractive system on which to build gene delivery vectors. We have therefore undertaken a study to identify the cis elements required for MHV-68 genome replication and packaging. Here we report that an 8.4-kb MHV-68 genomic fragment between ORF66 and ORF73 conferred on the plasmid the ability to replicate; replication required the presence of either de novo viral infection or viral reactivation from latency. We further mapped the origin of lytic replication (oriLyt) to a 1.25-kb region. Moreover, we demonstrated that the terminal repeat of the viral genome is sufficient for packaging of the replicated oriLyt plasmid into mature viral particles. Functional identification of the MHV-68 oriLyt and packaging signal has laid a foundation for investigating the mechanisms controlling gammaherpesvirus DNA replication during the viral lytic phase and will also serve as a base on which to design gene delivery vectors.

Rta of the human herpesvirus 8/Kaposi sarcoma-associated herpesvirus up-regulates human interleukin-6 gene expression.

Human herpesvirus 8 (HHV-8)/Kaposi sarcoma-associated herpesvirus (KSHV) is linked to a number of malignancies thought to be driven by cytokines, including interleukin-6 (IL-6). Rta, a transcriptional activator encoded by HHV-8/KSHV, activates the viral lytic cycle leading to the expression of several viral genes implicated in viral pathogenesis. However, the effect of HHV-8/KSHV Rta on cellular genes has not been reported. We present evidence that the human IL-6 (hIL-6) gene is up-regulated by Rta. Rta potently activated (up to 164-fold) the hIL-6 promoter in a dose-dependent manner in a transient transfection reporter system. Rta also induced expression of the endogenous hIL-6 gene, as shown by enzyme-linked immunosorbent assays. Activation of the hIL-6 gene by HHV-8/KSHV supports the role of hIL-6 in the development of these malignancies.

Transcriptional regulation of the interleukin-6 gene of human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus).

Human herpesvirus 8 (HHV-8; Kaposi's sarcoma-associated herpesvirus is linked to Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD), all of which are viewed as cytokine-driven malignancies. In particular, interleukin-6 (IL-6) has been found to promote the growth and proliferation of cells from KS and PEL. HHV-8 encodes a homologue of IL-6 (viral IL-6 [vIL-6]), which functions similarly to the cellular IL-6. Therefore, vIL-6 has been proposed to play an important role in tumor progression. Several groups have reported that vIL-6 is expressed from the HHV-8 genome at higher levels in PEL and MCD lesions than in KS lesions. However, it is not clear how vIL-6 expression is regulated. We characterized the transcription at the vIL-6 gene locus by Northern blot analysis and, in contrast to previous reports, we observed two distinct transcripts from induced PEL cell lines. This observation was confirmed by primer extension, as well as 5' and 3' rapid amplification of cDNA ends. Two transcription initiation sites and putative TATA boxes were mapped. A luciferase reporter system was used to show that each of the two putative TATA boxes contributed to vIL-6 promoter activity. Since virally encoded transcriptional activator Rta potently activates the viral lytic gene expression cascade, we examined the role of Rta in controlling vIL-6 gene expression and found that Rta activated the vIL-6 promoter. The Rta-responsive element was further mapped through a series of deletion constructs. Electrophoretic mobility shift assays demonstrated that Rta binds directly to the vIL-6 Rta-responsive element, and the core Rta-responsive element was mapped to a 26-bp region spanning from nucleotide 18315 to 18290 on the viral genome. We propose that the existence of two vIL-6 promoters offers opportunities for differential regulation of vIL-6 gene expression in different tissue types and may account for the variable vIL-6 levels observed in KS, PEL, and MCD.