IgM immunoblotting and polymerase chain reaction (PCR) were evaluated for use in diagnosing congenital syphilis, and the prevalence of central nervous system (CNS) invasion by Treponema pallidum during congenital infection was examined. The results of rabbit infectivity testing (RIT) on serum and cerebrospinal fluid (CSF) of 19 infants born to mothers with untreated early syphilis were compared with results of PCR and IgM immunoblotting. Seven infants had clinical evidence of congenital syphilis supported by positive serum IgM immunoblot (7/7), PCR (6/7), and RIT (3/3). Six symptomatic infants (86%) had T. pallidum isolated from CSF by RIT; 5 of 6 RIT-positive CSF samples were positive by PCR, and 2 also were reactive by IgM immunoblot. In 12 asymptomatic infants, 5 (42%) had a reactive serum IgM immunoblot and in 4 of these IgM reactivity was the only evidence of congenital infection. CNS invasion by T. pallidum was uncommon among asymptomatic infants; only 1 (8%) was positive by CSF RIT. The excellent agreement between RIT and PCR further substantiates the use of PCR as a surrogate for RIT. Our data indicate that the diagnosis of asymptomatically infected neonates will require a comprehensive approach using assays for both specific neonatal IgM and T. pallidum DNA in serum and CSF.
Bone morphogenetic proteins (BMPs) are well known for their osteoinductive activity, yet harnessing this capacity remains a high-priority research focus. We present a novel technology that delivers high BMP-2 levels at targeted locations for rapid endochondral bone formation, enhancing our preexisting cell-based gene therapy system by microencapsulating adenovirus-transduced cells in nondegradable poly(ethylene glycol) diacrylate (PEGDA) hydrogels before intramuscular delivery. This study evaluates the in vitro and in vivo viability, gene expression, and bone formation from transgenic fibroblasts encapsulated in PEGDA microspheres. Fluorescent viability and cytotoxicity assays demonstrated >95% viability in microencapsulated cells. ELISA and alkaline phosphatase assays established that BMP-2 secretion and specific activity from microencapsulated AdBMP2-transduced fibroblasts were not statistically different from monolayer. Longitudinal transgene expression studies of AdDsRed-transduced fibroblasts, followed through live animal optical fluorescent imaging, showed that microencapsulated cells expressed longer than unencapsulated cells. When comparable numbers of microencapsulated AdBMP2-transduced cells were intramuscularly injected into mice, microcomputed tomography evaluation demonstrated that the resultant heterotopic bone formation was approximately twice the volume of unencapsulated cells. The data suggest that microencapsulation protects cells and prolongs and spatially distributes transgene expression. Thus, incorporation of PEGDA hydrogels significantly advances current gene therapy bone repair approaches.
Aim: To clinically validate the 40-gene expression profile (40-GEP) test for cutaneous squamous cell carcinoma patients and evaluate coupling the test with individual clinicopathologic risk factor-based assessment methods. Patients & methods: In a 33-site study, primary tumors with known patient outcomes were assessed under clinical testing conditions (n = 420). The 40-GEP results were integrated with clinicopathologic risk factors. Kaplan–Meier and Cox regression analyses were performed for metastasis. Results: The 40-GEP test demonstrated significant prognostic value. Risk classification was improved via integration of 40-GEP results with clinicopathologic risk factor-based assessment, with metastasis rates near the general cutaneous squamous cell carcinoma population for Class 1 and ≥50% for Class 2B. Conclusion: Combining molecular profiling with clinicopathologic risk factor assessment enhances stratification of cutaneous squamous cell carcinoma patients and may inform decision-making for risk-appropriate management strategies.
((64)Cu-DOTA)(n)-trastuzumab-(IRDye800)(m) may be an effective diagnostic imaging agent for staging HER-2-positive breast cancer patients and intraoperative resection.
This study demonstrates that a multimodality contrast agent is useful for early detection of metastatic disease, and has applications for intraoperative PCa treatment. Further agent optimization is necessary to enhance specificity, and provide validation for prostate and other LN metastasizing epithelial cancers.
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