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Tsai C.-L.,Chang Gung University | Chuang P.-C.,Chang Gung University | Chuang P.-C.,Center for Translational Research in Biomedical science | Kuo H.-K.,Chang Gung University | And 4 more authors.
Cornea | Year: 2015

Purpose: The aim of this study was to characterize stem cells from human exfoliated deciduous teeth (SHED) and to investigate the potential of SHED to differentiate toward corneal epithelium-like cells in vitro. Methods: Mesenchymal and embryonic stem cell markers were analyzed by flow cytometry. The SHED was cocultured in either a transwell noncontact system or in a mixed culture system with immortalized human corneal epithelial (HCE-T) cells to induce the epithelial transdifferentiation. Expression of the mature corneal epithelium-specific marker cytokeratin 3 (CK3) and corneal epithelial progenitor marker cytokeratin 19 (CK19) were detected by immunofluorescence and the reverse transcription-polymerase chain reaction, respectively. Results: SHED strongly expressed a set of mesenchymal stromal cell markers and pluripotency markers including NANOG and OCT-4. Seven days after the transwells were cocultured with HCE-T cells, SHED successfully upregulated epithelial lineage markers CK3 (16.6 ± 7.9%) and CK19 (10.0 ± 4.3%) demonstrating the potential for epithelial transdifferentiation, whereas CK3 and CK19 were barely expressed in SHED when cultured alone. Expression of transcript levels of CK3 and CK19 were significantly upregulated when SHED were transwell cocultured or mixed cultured with HCE-T cells by 7, 14, and 21 days. Conclusions: We have demonstrated that SHED retain the potential for transdifferentiation to corneal epithelium-like cells by in vitro coculture with immortal corneal epithelium cells. Thus, exfoliated teeth may be an alternative tissue resource for providing stem cells for potential clinical applications in ocular surface regeneration. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Lin P.,Texas | Chen W.,University of Texas Southwestern Medical Center | Yuan C.,NCI Inc | Monreal M.,Interpflow CorporationMiami | And 4 more authors.
Cytometry Part B - Clinical Cytometry | Year: 2015

Background: Major heterogeneity between laboratories in flow cytometry (FC) minimal residual disease (MRD) testing in plasma cell (PC) myeloma (PCM) is an unfortunate reality. Cytometry societies such as the International Clinical Cytometry Society and the European Society for Clinical Cell Analysis recognize a strong need to establish minimally acceptable requirements and recommendations to perform such complex testing. Methods: A group of 11 flow cytometrists currently performing FC testing in PCM despite different instrumentation, myeloma using MRD panel designs (≥ 6-color) and analysis software compared the procedures in their laboratories and reviewed the available literature to propose a consensus guideline on PCM MRD analysis and reporting. Results/Conclusion: Consensus guidelines are to employ a minimum of four initial gating parameters (CD38, CD138, CD45, and light scatters) within the same tube for the identification of the total PC compartment; to subsequently analyze potentially aberrant surface markers (that are virtually always more informative than cytoplasmic light chain analysis); to report the antigen expression pattern on neoplastic PCs as being reduced, normal or increased, when compared to a normal reference PC immunophenotype (obtained using the same instrument and parameters), and the percentage of neoplastic PCs over total plasma Consensus guidelines on minimal current and future MRD analyses should target a lower limit of detection of 0.001%, and ideally a limit of quantification of 0.001%, which requires at least 3 × 106 and 0.5 × 106 bone marrow cells to be acquired, respectively. © 2015 International Clinical Cytometry Society.

Pradhan D.,University of Pittsburgh | Pattnaik N.,Kalinga Hospital | Silowash R.,University of Pittsburgh | Mohanty S.K.,Core Diagnostics
Pathology Research and Practice | Year: 2015

IgG4-related disease (IgG4-RD) is a recently recognized systemic autoimmune disorder characterized by high levels of serum IgG4 and dense infiltration of IgG4-positive plasma cells in multiple organs. The condition was first described as a disease of the pancreas, and has since been recognized in various organ systems including the kidneys. IgG4 related kidney disease (IgG4-RKD) signifies any form of renal involvement by IgG4-RD. The most common renal involvement by IgG4-RD is tubulointerstitial nephritis. Glomerular disease, in particular membranous glomerulonephritis, may also be seen. Other co-existent glomerular diseases such as IgA nephropathy, membranoproliferative glomerulonephritis, and mesangioproliferative immune complex glomerulonephritis may be identified. IgG4-related plasma cell arteritis has also been noted in the kidney. As with IgG4-RD in general, IgG4 related kidney disease (IgG4-RKD) usually occurs in middle-aged to elderly men. Common findings in IgG4-RKD are plasma cell-rich interstitial inflammatory infiltrate either in a focal or diffuse pattern with increased IgG4+ plasma cells, expansile swirling interstitial fibrosis, high levels of serum IgG and IgG4, hypocomplementemia, high serum IgE levels and/or peripheral blood eosinophilia. By immunofluorescence, most of the cases show IgG4 dominant tubular basement membrane immune complex deposits. Similar to IgG4-RD, IgG4-RKD often shows a rapid response to steroid therapy. In this review, we discuss the current knowledge on IgG4-RKD and its clinical relevance. © 2015 Elsevier GmbH.

Larson B.K.,Cedars Sinai Medical Center | Mohanty S.K.,Cedars Sinai Medical Center | Mohanty S.K.,Core Diagnostics | Wu J.M.,Cedars Sinai Medical Center | And 3 more authors.
APMIS | Year: 2016

Anal intraepithelial neoplasia (AIN) is a precursor to invasive anal squamous cell carcinoma. Histologic evaluation is hampered by intra- and interobserver variability. Various biomarkers have been investigated to improve the accuracy and reproducibility of diagnosis and grading, but interpretation can be challenging. ProEx™ C is an antibody cocktail for proteins upregulated in cervical intraepithelial neoplasia. This study investigated ProEx™ C's role alone and with p16 and Ki-67 in the diagnosis and grading of AIN. Sixty-seven anal tissue samples (22 AIN I, 25 AIN II/III, and 20 non-dysplastic) were stained for ProEx™ C, Ki-67, and p16. Staining patterns were recorded and correlated with morphologic diagnoses. Considering AIN II/III vs I, full-thickness ProEx™ C staining was more frequent in AIN II/III (p = 0.0373), and showed the highest sensitivity of the biomarkers. In combination with Ki-67, sensitivity was lower, but specificity for AIN II/III rose to 83%. For differentiating non-dysplasia from AIN I, negative ProEx™ C staining correlated with non-dysplasia (p < 0.0001) and had the highest sensitivity (90%). In combination with Ki-67, sensitivity dropped to 80%, but specificity was high (96%). ProEx™ C is useful for diagnosing and grading AIN, performing as well or better than other markers at identifying AIN II/III and non-dysplastic epithelium. © 2016 APMIS Published by John Wiley & Sons Ltd.

News Article | February 20, 2014
Site: yourstory.com

When we say India is a land of opportunity, there are a few sectors where this opportunity is more visible than others. Healthcare is a sector that holds promise. While healthcare is a broad area of opportunity, different verticals within the space have more potential. KPMG has pegged the healthcare diagnostics market to be worth $2.5 billion in 2012 and to grow in the region of 18-20% in the coming few years. And while there are well-known names in the usual diagnostics space, esoteric or specialised diagnostics is still an open field. It is in this green field that young Zoya Brar has set out to seek her fortune. The 24-year-old Zoya got hired by Google fresh out of college. She, however, quit in two years in March 2013 to found Core Diagnostics  – a clinical laboratory focused on next generation diagnostics for disease stratification and therapy selection. If you thought starting up in clinical diagnostics was a tough task, try telling this young girl that. Zoya, who is the youngest member in the team, says the way Core Diagnostics is different from the other diagnostic chains is because of its emphasis on being innovative. So within a few months of launching, the first thing Core Diagnostics has done is merge with Palo Alto, US-based diagnostics chain OncoMDx. This move was important to get access to the expertise of histo pathologists and super specialists who work in the US, says Zoya. “We could have always sent the patient report to the US for testing but that would have resulted in high costs for the customer. Instead, through this merger they now have access to experts sitting in the US, who can offer their services to Indian patients are a little incremental cost,[V1] ” she says. Core Diagnostics will leverage its partnership with OncoMDx to help patients who use Core Diagnostics services in India. Zoya says their focus is esoteric diagnostic because there exists a big gap in supply and demand in that space. She narrates an example of a woman who had a benign tumour in her breast, but was treated for breast cancer and also had to undergo mastectomy due to wrong diagnosis.  “That lady didn’t even need any treatment, but had to undergo so much mental and physical trauma because of wrong diagnosis,” explains Zoya. Another reference she cites is the emergence of branded hospital chains in India over the last few years. “If you go back 10 years and see how healthcare delivery has evolved in India all the hospitals that are well-known today, didn’t exist back then. We were living with what was available. Then hospitals like Fortis came to India resulting in a change in customer demand. If you had asked people 15 years ago whether this will work, they would have said it is too high end and we don’t need it. But today the scenario has changed.  This is how esoteric diagnostics will also evolve,” she reasons. India will be the main market for Core Diagnostics, but going forward they will offer services in the US as well. Besides their panel of specialists in the US, Core Diagnostic has a team of 30 in India who handle affairs of the startup here. The team is a mix of people from various backgrounds, including pharma, medical devices, IT and healthcare delivery among others. “If you go to other pathologies, there is a certain way they hire. But clearly those labs are not doing all the things right. So we wanted a team from different backgrounds so as to allow lot of innovation to happen on a daily basis,” reasons Zoya. The startup has taken the below-the-line approach to publicise itself and Zoya says they will continue with this strategy for some time. One-to-one meetings with doctors to inform them about Core Diagnostic are also being adopted. Zoya says expanding to all major metros within India is on the cards in the near future. However, as they grow their expansion strategy will be three-pronged – on geography, technology and clinical options. Geographic expansion will mostly be through company-owned outlets so that the quality of service delivery can be well-managed. Core Diagnostics received a funding of $5 million from Artiman Ventures in the beginning and is on the lookout for fresh funding. While the journey has had its share of challenges, Zoya admits that hiring was the biggest of them all. It did not help that people in the diagnostics industry are mostly senior professionals and a 20-year-old taking their job interview was not something they had expected. Zoya found a way to work around this problem by getting her VCs and advisory board members to conduct the interviews. “Talking to VCs is the easy part because they like to invest in people, not the idea or the company. But yes, hiring team members was a challenge. We used some tricks in the book, but managed to do a good job,” she says.

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