The clinical, pathologic, and molecular features of pleomorphic lobular carcinoma in situ (PLCIS) and the relationship of PLCIS to classic LCIS (CLCIS) are poorly defined. In this study, we analyzed 31 cases of PLCIS (13 apocrine and 18 non-apocrine subtypes) and compared the clinical, pathologic, immunophenotypic and genetic characteristics of these cases with those of 24 cases of CLCIS. Biomarker expression was examined using immunostaining form E-cadherin, GCDFP-15, ER, PR, AR, HER2, CK5/6, and Ki67. Array-based comparative genomic hybridization (aCGH) to assess genomic alterations was performed usingm microdissected formalin-fixed paraffin-embedded samples. Patients with PLCIS presented with mammographic abnormalities. Histologically, the tumor cells were dyshesive and showed pleomorphic nuclei, and there was often associated necrosis and microcalcifications. All lesions were E-cadherin negative. Compared to CLCIS, PLCIS showed significantly higher Ki67 index, lower ER and PR expression, and higher incidence of HER2 gene amplification. The majority of PLCIS and CLCIS demonstrated loss of 16q and gain of 1q. Apocrine PLCIS had significantly more genomic alterations than CLCIS and non-apocrine PLCIS. Although lack of E-cadherin expression and the 16q loss and 1q gain-aCGH pattern support a relationship to CLCIS, PLCIS has clinical, mammographic, histologic, immunophenotypic and genetic features that distinguish it from CLCIS. The histologic features, biomarker profile, and genomic instability observed in PLCIS suggest a more aggressive phenotype than CLCIS. However, clinical follow-up studies will be required to define the natural history and most appropriate management of these lesions.
BackgroundMosquito biting frequency and how bites are distributed among different people can have significant epidemiologic effects. An improved understanding of mosquito vector-human interactions would refine knowledge of the entomological processes supporting pathogen transmission and could reveal targets for minimizing risk and breaking pathogen transmission cycles.Methodology and principal findingsWe used human DNA blood meal profiling of the dengue virus (DENV) vector, Aedes aegypti, to quantify its contact with human hosts and to infer epidemiologic implications of its blood feeding behavior. We determined the number of different people bitten, biting frequency by host age, size, mosquito age, and the number of times each person was bitten. Of 3,677 engorged mosquitoes collected and 1,186 complete DNA profiles, only 420 meals matched people from the study area, indicating that Ae. aegypti feed on people moving transiently through communities to conduct daily business. 10–13% of engorged mosquitoes fed on more than one person. No biting rate differences were detected between high- and low-dengue transmission seasons. We estimate that 43–46% of engorged mosquitoes bit more than one person within each gonotrophic cycle. Most multiple meals were from residents of the mosquito collection house or neighbors. People ≤25 years old were bitten less often than older people. Some hosts were fed on frequently, with three hosts bitten nine times. Interaction networks for mosquitoes and humans revealed biologically significant blood feeding hotspots, including community marketplaces.Conclusion and significanceHigh multiple-feeding rates and feeding on community visitors are likely important features in the efficient transmission and rapid spread of DENV. These results help explain why reducing vector populations alone is difficult for dengue prevention and support the argument for additional studies of mosquito feeding behavior, which when integrated with a greater understanding of human behavior will refine estimates of risk and strategies for dengue control.
Background: Facial skin exhibits unique biophysical properties that are distinct from skin belonging to other areas of the body. Small to large regional differences in biophysical properties between facial sites are observed. Technological advances in dermatological research allow a quantitative study of the biophysical qualities of the face and its relation to skin elsewhere. However, comprehensive studies examining inter-regional variations using each of the six standard biophysical parameters have been few. We summarize findings on the biophysical parameters used to explore the human face as well as regional differences in skin reactivity to chemical irritants. Methods: We performed a literature search using Pubmed, Embase, Science Citations Index, and the UCSF's dermatological library on biophysical parameters and skin physiology pertaining to the human face. Results: Distinct regional differences in transepidermal water loss (TEWL), capacitance, blood flow, sebum, pH, and temperature were demonstrated in facial skin. However, studies cannot be compared with each other because each uses different anatomical sites, skin conditions, and measurement techniques. Intraregional differences in TEWL, sebum, and temperatures were observed
Array-based comparative genomic hybridization (CGH) is a technique that allows genome wide screening of gains and losses in DNA copy number. In cases where multiple tumors are encountered, this genetic technique may prove useful in differentiating new primary tumors from recurrences. In this case report, we used arraybased CGH to examine the genomic relationships among two leiomyosarcomas and two breast cancers in the same patient, three of which were diagnosed synchronously. Array-based CGH was performed on the four tumor samples using random prime amplified microdissected DNA. Samples were hybridized onto bacterial artificial chromosome arrays composed of approximately 2400 clones. Patterns of alterations within the tumors were compared and genetic alterations among the leiomyosarcomas and breast lesions were found. Overall, three distinct genetic profiles were observed. While the two leiomyosarcomas shared a similar pattern of genetic alterations, the two invasive breast lesions did not. The nearly identical pattern of genetic alterations belonging to the two metachronous leiomyosarcomas confirmed metastatic recurrence while the two different genetic profiles of the invasive ductal carcinomas suggest that the two lesions represented two distinct foci of multifocal disease rather than clonal extension of the primary tumor. We conclude that genetic analysis by array-based CGH can clearly elucidate the relationships between multiple tumors and may potentially serve as an important clinical tool. Modern Pathology (2005) 18, 591-597, advance online publication, 14 January 2005; doi:10.1038/modpathol.3800332 Keywords: breast cancer; comparative genomic hybridization; leiomyosarcoma Comparative genomic hybridization (CGH) is a technique that has greatly facilitated detection of gains and losses in DNA copy number, and has been of particular utility in elucidating the pattern of genomic alterations in tumors. Although this technique remains primarily a research tool, it has potential clinical use in cases with complex presentation. Array CGH may be of clinical value in differentiating new primary tumors from recurrent lesions, particularly in patients with unusual recurrence patterns. Genomic analysis can also help elucidate the relationship between multiple tumor foci. These determinations may in some cases significantly alter the course of further treatment. Array CGH can thus serve as an important adjunct to immunohistochemistry and histopathology. In this study, we examined the genomic relationships between four separate cancers in the same patient, using array CGH. This case illustrates the potential clinical application of genomic technology in defining the relationship between multiple tumors. Case reportA 43-year old woman 5 years status post resection of a high-grade left retroperitoneal leiomyosarcoma presented with masses in the left breast and right thigh. Mammography showed a highly suspicious spiculated lesion in the lower inner left breast, corresponding to the palpable mass. Fineneedle aspiration of t...
The 3% antioxidant solution possesses a significant antioxidative capacity, which was 2.5 times greater than the known antioxidant idebenone in a 1% solution as shown by the quenching of superoxide anion radicals measured by photochemiluminescence. This method provides rapid, accurate, and sensitive measurement of the antioxidant properties of lipid-soluble compounds.
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