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Methylation profiling of benign and malignant breast lesions and its application to cytopathology. 总被引:9,自引:0,他引:9
Robert T Pu Lauren E Laitala Patricia M Alli Mary Jo Fackler Saraswati Sukumar Douglas P Clark 《Modern pathology》2003,16(11):1095-1101
Methylation of tumor suppressor genes has been implicated in breast cancer development. However, methylation profiles of different breast lesions, subtypes of carcinoma in particular, have not been examined in detail. In this study, we use methylation-specific PCR (MSP) to generate gene methylation profiles of different breast lesions and to test the clinical utility of such profiles. We examined the methylation status of three genes, RARbeta2, RASSF1A, and cyclin D2, on 102 samples of breast tissue, from benign (n = 36), to in situ carcinoma (n = 21), to invasive carcinoma (n = 45). We found that almost all cases of invasive carcinoma (96%) contained at least one methylated gene from our panel, whereas gene methylation was less common among benign lesions (42%) and in situ carcinoma (76%). Of the three genes, cyclin D2 methylation was most specific for malignancy because only 1 of 35 benign cases was methylated at this gene (1 case was not informative). The major histologic subtypes of invasive carcinoma show similar methylation profiles in the genes examined. We next performed MSP analysis on archival breast fine-needle aspiration (FNA) biopsy samples and corresponding surgical biopsy specimens and found a high concordance between the two types of specimens. We then analyzed 17 breast FNA biopsy samples with an indeterminate diagnosis. In this setting, MSP had a high specificity (100%) and modest sensitivity (67%) for identifying malignancy. 相似文献
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As recently as 1980, gonorrhea ranked first among communicable diseases in the U.S.A. More alarming was the fact that 75 to 80 percent of infected females were reported to be asymptomatic. As more of these asymptomatic individuals were discovered, the tendency to do routine gonococcal screening in women increased. Of late, however, the trend to abstain from doing routine gonococcal screening has become more evident because of the low yield of positive cultures in the majority of the population screened. The St. Joseph's Medical Center is a single residency (Family Practice) teaching hospital serving the community of Yonkers, N.Y. The St. Joseph's Family Health Center serves as the model unit where our residents work and is also the main outpatient facility of the hospital. The objective of our study was to determine the incidence of asymptomatic gonorrhea prospectively and randomly, in our female patients, to form guidelines to separate high from low risk patients, and to discuss the question of whether gonococcal screening should be performed routinely in females. 相似文献
5.
S.A. Syam Kumar Prabakar Sukumar Padmanaban Sriram Dhanabalan Rajasekaran Srinu Aketi Nagarajan Vivekanandan 《Medical Dosimetry》2012,37(4):436-441
The recalculation of 1 fraction from a patient treatment plan on a phantom and subsequent measurements have become the norms for measurement-based verification, which combines the quality assurance recommendations that deal with the treatment planning system and the beam delivery system. This type of evaluation has prompted attention to measurement equipment and techniques. Ionization chambers are considered the gold standard because of their precision, availability, and relative ease of use. This study evaluates and compares 5 different ionization chambers: phantom combinations for verification in routine patient-specific quality assurance of RapidArc treatments. Fifteen different RapidArc plans conforming to the clinical standards were selected for the study. Verification plans were then created for each treatment plan with different chamber-phantom combinations scanned by computed tomography. This includes Medtec intensity modulated radiation therapy (IMRT) phantom with micro-ionization chamber (0.007 cm3) and pinpoint chamber (0.015 cm3), PTW-Octavius phantom with semiflex chamber (0.125 cm3) and 2D array (0.125 cm3), and indigenously made Circular wax phantom with 0.6 cm3 chamber. The measured isocenter absolute dose was compared with the treatment planning system (TPS) plan. The micro-ionization chamber shows more deviations when compared with semiflex and 0.6 cm3 with a maximum variation of ?4.76%, ?1.49%, and 2.23% for micro-ionization, semiflex, and farmer chambers, respectively. The positive variations indicate that the chamber with larger volume overestimates. Farmer chamber shows higher deviation when compared with 0.125 cm3. In general the deviation was found to be <1% with the semiflex and farmer chambers. A maximum variation of 2% was observed for the 0.007 cm3 ionization chamber, except in a few cases. Pinpoint chamber underestimates the calculated isocenter dose by a maximum of 4.8%. Absolute dose measurements using the semiflex ionization chamber with intermediate volume (0.125 cm3) shows good agreement with the TPS calculated among the detectors used in this study. Positioning is very important when using smaller volume chambers because they are more sensitive to geometrical errors within the treatment fields. It is also suggested to average the dose over the sensitive volume for larger-volume chambers. The ionization chamber-phantom combinations used in this study can be used interchangeably for routine RapidArc patient-specific quality assurance with a satisfactory accuracy for clinical practice. 相似文献
6.
Qiang Zeng Yue-Harn Ng Tripti Singh Ke Jiang Khaleefathullah A. Sheriff Renee Ippolito Salwa Zahalka Qi Li Parmjeet Randhawa Rosemary A. Hoffman Balathiripurasundari Ramaswami Frances E. Lund Geetha Chalasani 《The Journal of clinical investigation》2014,124(3):1052-1056
Chronic rejection is the primary cause of long-term failure of transplanted organs and is often viewed as an antibody-dependent process. Chronic rejection, however, is also observed in mice and humans with no detectable circulating alloantibodies, suggesting that antibody-independent pathways may also contribute to pathogenesis of transplant rejection. Here, we have provided direct evidence that chronic rejection of vascularized heart allografts occurs in the complete absence of antibodies, but requires the presence of B cells. Mice that were deficient for antibodies but not B cells experienced the same chronic allograft vasculopathy (CAV), which is a pathognomonic feature of chronic rejection, as WT mice; however, mice that were deficient for both B cells and antibodies were protected from CAV. B cells contributed to CAV by supporting splenic lymphoid architecture, T cell cytokine production, and infiltration of T cells into graft vessels. In chimeric mice, in which B cells were present but could not present antigen, both T cell responses and CAV were markedly reduced. These findings establish that chronic rejection can occur in the complete absence of antibodies and that B cells contribute to this process by supporting T cell responses through antigen presentation and maintenance of lymphoid architecture. 相似文献
7.
Diagnostic utility of testosterone priming prior to dynamic tests to differentiate constitutional delay in puberty from isolated hypogonadotropic hypogonadism
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8.
Binod C. Raulo Chidananda Dash Shakti Rath Sukumar Chakrabarty Padmanav Rautray Jagannath Sahoo Rabindra N. Padhy 《急性病杂志》2012,1(2):156-158
This is an attempt of using in vitro cultured mesenchymal stem cells (MSCs) from bone marrow in joining of a fracture non-union. Bone marrow cells were obtained and differentially centrifuged for MSCs that were grown in vitro in mesenchymal stem cell basal medium aseptically, for 10 d. The cell mass was injected around the fracture non-union. Healthy conditions of development of tissue regeneration at the trauma site and due bone joining were recorded. It is concluded that in vitro cultured MSCs had a blithesome effect on the fracture non-union. 相似文献
9.
Joao B. Augusto Nicolas Johner Dipen Shah Sabrina Nordin Kristopher Knott Stefania Rosmini Clement Lau Mashael Alfarih Rebecca Hughes Andreas Seraphim Ravi Vijapurapu Anish Bhuva Linda Lin Natalia Ojrzyńska Tarekegn Geberhiwot Gabriella Captur Uma Ramaswami Richard P. Steeds Mehdi Namdar 《Molecular genetics and metabolism》2021,132(2):S17-S18
10.
Sukumar Kandasamy Kuldeep S Chattha Anastasia N Vlasova Gireesh Rajashekara Linda J Saif 《Gut microbes》2014,5(5):639-651
B cells play a key role in generation of protective immunity against rotavirus infection, a major cause of gastroenteritis in children. Current RV vaccines are less effective in developing countries compared to developed countries. Commensals/probiotics influence mucosal immunity, but the role of early gut colonizing bacteria in modulating intestinal B cell responses to RV vaccines is largely unknown. We co-colonized neonatal gnotobiotic pigs, the only animal model susceptible to HRV diarrhea, with 2 dominant bacterial species present in the gut of breastfed infants, Lactobacillus rhamnosus strain GG and Bifidobacterium animalis lactis Bb12 to evaluate their impact on B cell responses to an attenuated (Att) human rotavirus (HRV) Wa strain vaccine. Following HRV challenge, probiotic-colonized, AttHRV vaccinated piglets had significantly lower fecal scores and reduced HRV shedding titers compared to uncolonized, AttHRV vaccinated pigs. The reduction in HRV diarrhea was significantly correlated with higher intestinal IgA HRV antibody titers and intestinal HRV-specific IgA antibody secreting cell (ASC) numbers in probiotic-colonized, AttHRV vaccinated pigs compared to uncolonized, vaccinated pigs. The significantly higher small intestinal HRV IgA antibody responses coincided with higher IL-6, IL-10 and APRIL responses of ileal mononuclear cells (MNCs) and the immunomodulatory effects of probiotics genomic DNA on TGF-β and IL-10 responses. However, serum RV IgG antibody titers and total IgG titers were significantly lower in probiotic-colonized, AttHRV vaccinated pigs compared to uncolonized, vaccinated pigs, both pre- and post-challenge. In summary, LGG and Bb12 beneficially modulated intestinal B cell responses to HRV vaccine. 相似文献