North American Journal of Medicine and Science
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Non-Invasive Prenatal Diagnosis: A Comparison of Cell Free Fetal DNA (cffDNA) Based Screening and Fetal Nucleated Red Blood Cell (fnRBC) Initiated Testing
Get PDFCurrent prenatal diagnosis uses non-invasive procedures of maternal serum screening and ultrasound exam to evaluate the risk of chromosomal abnormalities and invasive procedures of chorionic villus sampling and amniocentesis for the diagnosis of cytogenomic abnormalities and gene mutations. The discovery of cell free fetal DNA (cffDNA) in maternal blood prompted the application of massive parallel sequencing to screen fetal aneuploidies. The multi-center large-scale validation of cffDNA based prenatal screening has resulted in rapid integration of this close-to-diagnostic non-invasive procedure into clinical application. Further improvement of this approach could lead to the screening of pathogenic copy number variants and known disease-causing gene mutations. The success from cffDNA fuels efforts in isolating circulating fetal nucleated red blood cells (fnRBCs) for direct non-invasive prenatal testing of fetal genetic disorders. Various isolation and enrichment methods based on the physical and biologic features of the fnRBCs have been developed but the analytic and clinical validities have not yet been established. The cffDNA based prenatal screening has significantly reduced unnecessary invasive procedures. Future breakthrough on fnRBC initiated prenatal testing will further shift the paradigm toward non-invasive prenatal diagnosis. [N A J Med Sci. 2013;6(4):194-199. DOI: 10.7156/najms.2013.0604194
De-SUMOylation on ATF3 Enhances p53-ATF3 Binding and Trans-activation of p53 Responsive Promoter but not p53 Stability
No full textCyclic AMP-dependent transcription factor-3 (ATF3), a stress sensor and mediator, plays an essential role in cells to maintain homeostatsis and has diverse functions in cellular survival and death signal pathways. Previously, we demonstrated that ATF3 can be SUMOylfigated in vitro and in vivo and lysine 42 is the main SUMO site. Several reports have shown that ATF3 is a novel regulator of p53 protein stability and function; however, the role of ATF3 SUMOylation on ATF3-p53 interaction and p53 stability as well as p53-dependent transcriptional activity remains unknown. Here we report that de-SUMOylation of ATF3 enhanced ATF3-p53 physical interaction. While overexpression of ATF3 stabilizes p53, SUMOylation status of ATF3 does not alter ATF3-mediated p53 stability. Interestingly, de-SUMOylation of ATF3 augmented trans-activation of p53 responsive promoters, including natural p53-dependent promoters. Taken together, we provide the evidence that SUMOylation of ATF3 regulates ATF3-p53 interaction and transactivation of p53 responsive promoter
Establishing the First Diagnosis of Follicular Thyroid Carcinoma from the Femoral Metastatic Site in an 84-year-old Woman
Get PDFFollicular thyroid carcinoma (FTC) commonly presents as a solitary thyroid nodule, which is diagnosed by thorough examination of thyroidectomy/lobectomy specimen for capsular and vascular invasions. First diagnosis of FTC from femoral metastasis is very rare. Here, we report such a case in an 84-year-old woman who presented with increasing pain in her left thigh. A bone scan revealed multiple lesions in the bones including left femur. Four years ago, the patient suffered right humeral pathological fracture. The humeral lesion was positive for TTF-1 and was interpreted as “metastatic non-small cell carcinoma consistent with lung primary”. However, subsequent bronchial washing and lung biopsy were negative for malignancy. Biopsy of left femoral lesion showed solid nests of cells with round to oval nuclei and abundant eosionophilic/granular cytoplasm. The nuclei of tumor cells contain one or more nucleoli and granular/vesicular chromatin. No typical nuclear morphology of papillary thyroid carcinoma (PTC) was noted. The tumor cells are positive for thyroglobulin and TTF-1, consistent with metastatic tumor from thyroid primary. Immunostains of HBME-1 and CK19 only mark scattered tumor cells, which do not support the differential diagnosis of metastatic PTC. CD56 and CK7 stains are both positive. Upon further communication, patient's remote history of “thyroid follicular adenoma”, status post right lobectomy was obtained. The femoral lesion was negative for BRAF mutation. In conclusion, based on the overall morphological and immunohistochemical features as well as patient’s history, the final diagnosis of metastatic FTC was made. We would like to raise the awareness that metastatic FTC should be included in the differential diagnoses for tumors metastasized to bone to avoid misdiagnosis
Roles of Peripheral Blood CD34+ Cell Count and Midpoint Collection CD34+ Cell Yield for Peripheral Blood Stem Cell Collections from Autologous Patients Mobilized by G-CSF and Plerixafor
Get PDFAutologous peripheral blood stem cell transplantation is used to treat multiple hematologic malignancies including multiple myeloma, lymphomas and amyloidosis. G-CSF plus plerixafor has increasingly become a viable first-line PBSC mobilization option in the autologous patients. The aim of our study was to determine whether peripheral blood CD34+ cell count (PB CD34) or midpoint collection CD34+ yield (MPY) is a better predictor of the final collection CD34+ yield (FY) to guide decision-making to ensure collection target achievement and, when possible, to reduce collection sessions for adult autologous PBSC patients mobilized with both G-CSF and plerixafor. Eighty-eight autologous patients who were mobilized by the 2-pronged regimen underwent 171 PBSC collection sessions in 2011. Retrospective data analysis for the PBSC collections showed: (1) Both PB CD34 and MPY correlate strongly with FY; (2) Reduction of apheresis sessions in 24 patients was achieved by decision-making based on FY estimation using PB CD 34 and/ or MPY. Reduction of apheresis sessions decreases the discomfort, inconvenience, cost, and time spent associated with the stem cell collection for the patients, and also decreases the cost and increases the efficiency of our apheresis operation. Based on the prediction value of either PB CD34 or MPY, a guideline is developed for our apheresis facility for autologous PBSC patients, and 1 increased TBV is preferred at most of the time.
History of the Association of Chinese Geneticists in America (ACGA)
Get PDFThe Association of Chinese Geneticists in America (ACGA) is a non-profit (501C) organization formed by a group of American geneticists of Chinese ethnicity but its membership is open to individuals of all races and ethnicity. Incorporated in the State of Georgia in 1987, ACGA is supported by membership fees and donations. The Association facilitates the interaction between the American genetics community and their colleagues in mainland China, Taiwan, Hong Kong and Singapore. [N A J Med Sci. 2013;6(4):171-172.
Opportunities and Challenges in Molecular Genetic Testing in China: The Experience of an Academic Center for Clinical Molecular Medicine
Get PDFMolecular genetic testing and molecular pathology are relatively new but rapidly growing fields in China. This article reports on the experience of providing molecular genetic testing at the Center for Clinical Molecular Medicine (CCMM) of Chongqing Medical University in China. This center is the first of such centers in the southwestern region of China and implements a spectrum of genetic tests on constitutional cytogenetics, oncology cytogenetics, molecular cytogenetics, molecular genetics, molecular oncology, metabolic genetics, and newborn screening. The annual test volume had a 78-fold increase in the past five years and reached approximately 380,000 tests in 2012. This tremendous growth reflects both great opportunities and challenges for China’s healthcare system. Some of the challenges such as the lack of a medical genetics professionals and qualified training programs for clinical geneticists, laboratory specialists and genetic counselors are discussed.
Prevalence and Significance of Abnormal Tactile Responses in Young Children with Autism
Get PDFWith the inclusion of sensory abnormalities in the DSM-V criteria for autism, the multifocal touch/pain abnormalities reported in young children with autism are no longer comorbid symptoms, and it has become an urgent priority to identify their nature and significance. A recent study differentiated children with autism from typical and otherwise developmentally delayed groups on the two-fold basis of mixed allodynia and hypoesthesia, and severe global self-regulatory delay. In this study, we retrospectively analyzed case records for 266 pre-school children with autism and typical development to verify recent findings, assess the prevalence and location of tactile abnormalities in the autism group, and explore the relationship between tactile abnormalities and self-regulatory delay. Results differentiated the autism group by severity of tactile abnormality [F(1,262) = 172.8, p < .001] and self-regulatory delay [F(1,262) = 232.8, p < .001]. Allodynia was reported in 100% of the autism group by parent report and 98% by therapist report; hypoesthesia was present in 65% by parent report. Tactile abnormalities were directly, linearly related to self-regulatory delay (r = .727, p < .001) in both groups. The sense of touch has not been fully evaluated in autism, and there is insufficient quantitative evidence to conclude that it is intact. Mixed allodynia and hypoesthesia are typical signs of sensory neuropathy. Evidence of their near universal presence in young children with autism, and direct relationship to self-regulatory delay underscores the urgent need to fully evaluate the sense of touch in autism and rule out sensory neuropathy. [N A J Med Sci. 2013;6(3):121-127. DOI: 10.7156/najms.2013.0603121
Stress and Mental Flexibility in Autism Spectrum Disorders
Get PDFCognitive deficits are well-established core features in autism spectrum disorders (ASD). In this paper, we review representative studies on cognitive flexibility, which is one type of neuropsychological weakness that is often related to repetitive and restricted clinical symptoms in ASD. We also review effects of stress in both typically developing individuals and in individuals with ASD, to show the importance of this factor in modulating relationships between cognitive inflexibility and clinical symptoms related reflecting inflexibility, such as repetitive and restricted behaviors. Finally, we present three case vignettes involving higher functioning individuals to illustrate some of these relationships in individuals, and to suggest the utility of clinical interventions. [N A J Med Sci. 2013;6(3):145-153. DOI: 10.7156/najms.2013.0603145
Stability and Reproducibility of the Measurement of Plasma Nitrate in Large Epidemiologic Studies
Get PDFInorganic nitrate has emerged as a therapeutic agent for cardiovascular disease; however, nitrate can also metabolize to carcinogenic nitrosamines under pathologic conditions. Few large epidemiologic studies have examined circulating levels of nitrate in relation to cardiovascular disease and cancer. Data on the validity of nitrate measurement in blood samples collected in typical epidemiologic settings are needed before nitrate can be evaluated as an exposure in large epidemiologic studies.We measured plasma levels of nitrate in three pilot studies to evaluate its laboratory variability, stability with delayed processing, and reproducibility over time among women from the Nurses’ Health Study and healthy female volunteers.Laboratory variability of nitrate levels was fairly low, with a coefficient variation (CV) of 7%. Plasma nitrate levels in samples stored as whole blood on ice for up to 48 hrs before processing were very stable; the overall intra-class correlation (ICC) from 0 to 48 hours was 0.89 (95%CI, 0.70-0.97). The within-person reproducibility over a one-year period was modest, with an ICC of 0.49 (95% CI, 0.33- 0.94). Our results indicate that measurement of nitrate in plasma is reliable and stable in blood samples with delayed processing up to 48 hours. Within-person reproducibility was modest but data from this study can be used for measurement error correction in subsequent analyses. The measurement of nitrate cannot be widely used in epidemiologic research without the documentation of its stability and reproducibility. [N A J Med Sci. 2013;6(2):82-86. DOI: 10.7156/najms.2013.0602082
Neuroepithelial Structures Similar to Juxtaoral Organ of Chievitz Present in the Mandibular Torus of a 41-year-old Man
Get PDFThe Juxtaoral organ of Chievitz (JOOC) is a normal neuroepithelial structure that is located in the pterygomandibular space. Neuroepithelial structures resembling those seen in the Juxtaoral organ of Chievitz in other locations are diagnostically challenging and can be potentially misdiagnosed as squamous cell carcinoma. Here, we report the first case of such structures presenting on the right lingual surface of the mandible of a 41-year-old man with torus mandibularis. Awareness of the possibility that neuroepithelial structures similar to the JOOC may be found in mandibular tori will prevent unwarranted costly diagnostic procedures and unnecessary surgical interventions. [N A J Med Sci. 2013;6(2):100-102. DOI: 10.7156/najms.2013.0602100