Recent Publications by CFE Educators

The cooperative activity of protein tyrosine kinases and phosphatases plays a central role in regulation of T cell receptor (TCR) signal strength. Perturbing this balance, and thus the threshold for TCR signals, has profound impacts on T cell development and function. We previously generated mice containing a point mutation in the juxtamembrane wedge of the receptor-like protein tyrosine phosphatase CD45. Demonstrating the critical negative regulatory function of the wedge, the CD45 E613R (WEDGE) mutation led to a lymphoproliferative disorder (LPD) and a lupus-like autoimmune syndrome. Using genetic, cellular, and biochemical approaches, we now demonstrate that the CD45 wedge influences T cell development and function. Consistent with increased TCR signal strength, WEDGE mice have augmented positive selection and enhanced sensitivity to the CD4-mediated disease experimental autoimmune encephalitis (EAE). These correspond with hyperresponsive calcium and pERK responses to TCR stimulation in thymocytes, but surprisingly, not in peripheral T cells, where these responses are actually depressed. Together, the data support a role for the CD45 wedge in regulation of T cell responses in vivo and suggest that its effects depend on cellular context.

BACKGROUND AIMS

The thymidine analog bromodeoxyuridine (5-bromo-2-deoxyuridine; BrdU) has been used widely to label cells in culture and in tissue. The labeled cells can also be tracked when transplanted into a suitable host. In the present study we tested a new thymidine analog, 5-ethynyl-2-deoxyuridine (EdU), for labeling and tracking of mesenchymal stromal cells (MSC), specifically adipose tissue-derived stem cells (ADSC).

METHODS

Labeling of ADSC was examined for the dosage effect of EdU and stability of label by Alexa-594 staining followed by fluorescence microscopy. Labeling of various organs/tissues was done by intraperitoneal injection of EdU and examined by histology and fluorescence microscopy. Tracking of ADSC was done by intratissue or intravenous transplantation of EdU-labeled ADSC into various tissues and examined by histology and fluorescence microscopy.

RESULTS

EdU was incorporated specifically into the nucleus in approximately 50% of ADSC and the percentage of cells that remained fully labeled declined with time. Peritoneal injection of EdU resulted in the appearance of EdU-positive cells in most organs and tissues. In the intestine, EdU-positive cells were found in both the epithelium and connective tissues 7 h after injection. Long-term (2-6 week) follow-ups found EdU-positive cells only in the connective tissue. Tracking of ADSC was successful in tissues 10 weeks after intratissue or intravenous transplantation.

CONCLUSIONS

Cell labeling with EdU in culture or living animals can be performed easily. The detection of EdU label requires no harsh treatment or immunologic reaction, as detection of BrdU label does. EdU can be used for long-term tracking of ADSC.

PURPOSE OF REVIEW

Recent studies have demonstrated racial/ethnic and socioeconomic disparities in adults undergoing thyroidectomy and parathyroidectomy. To date, few studies have examined outcomes in children undergoing cervical endocrine surgery.

RECENT FINDINGS

Children undergoing thyroidectomy and parathyroidectomy have higher complication rates than adults undergoing similar procedures. Complication rates appear to be lower when procedures are performed by high-volume surgeons. Access to high-volume surgeons continues to be limited for children of racial/ethnic minorities and in families of a lower socioeconomic status.

SUMMARY

Complications following thyroidectomy and parathyroidectomy in children can have profound, life-long effects on development and quality of life. Outcomes are optimized when surgery is performed by high-volume surgeons. Obtaining access to high-volume surgeons requires a multidisciplinary approach by parents, pediatricians, pediatric endocrinologists, and third-party payers.

PURPOSE OF REVIEW

Medullary thyroid cancer (MTC) is derived from the parafollicular cells of the thyroid. Understanding the molecular biology behind specific mutations of the RET gene and their prognostic implications have led to the establishment of tailored treatment modalities for certain patients. We review the most recent studies on the molecular biology, calcitonin screening, diagnosis, imaging, and treatment of MTC.

RECENT FINDINGS

Newly identified rearranged during transfection point mutations have helped with MTC prognosis and have resulted in the establishment of new treatment guidelines. Screening for MTC in the United States with basal serum calcitonin for patients with thyroid nodules would cost $11,793 per life-year saved (LYS), compared with colonoscopy and mammography screening. For metastatic or recurrent disease, neck ultrasound, chest computed tomography scan, liver MRI, bone scintigraphy, and axial skeleton MRI have been proven superior to 18F-FDG PET/computed tomography. For patients with nonoperable metastatic disease, novel chemotherapeutic agents, such as vandetanib, targeting rearranged during transfection, vascular endothelial growth factor receptor and epidermal growth factor receptor, are showing promise. Such agents are currently in phase II trials.

SUMMARY

There have been several recent advances in the diagnosis, molecular biology, imaging, and treatment options of MTC. By potentially downstaging of disease, and treating metastatic disease more effectively, overall survival and outcomes of patients may improve.