Stability of variables associated with the metabolic syndrome from adolescence to adulthood: the Aerobics Center Longitudinal Study.

The purpose of the study was to examine the stability of variables associated with the metabolic syndrome from adolescence to adulthood. The sample included 48 subjects from the Aerobics Center Longitudinal Study who had one clinical visit during adolescence (mean age = 15.8 years) and a follow-up visit during adulthood (mean age = 26.6 years). The following variables were considered: treadmill time to exhaustion (TM), body mass index (BMI), waist circumference (WC), percent body fat (%BF), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC:HDL-C, triglycerides (TG), glucose (GLU), and systolic (SBP), diastolic (DBP), and mean (MAP) blood pressure. A composite risk factor score using variables consistent with the WHO and ATP III definition of the metabolic syndrome (WC, HDL-C, TG, MAP, and GLU) was calculated. Tracking coefficients were computed as partial correlations, controlling for length of follow-up (mean = 11 years). Tracking coefficients (r values) were moderate for all variables (TM, 0.53; BMI, 0.64; WC; 0.79;%BF, 0.44; TC, 0.62; HDL-C, 0.60; TG, 0.54; TC:HDL-C, 0.78; SBP, 0.45; and MAP, 0.41), except GLU (0.26) and DBP (0.21). The composite risk factor score also tracked moderately well (0.56) from adolescence into adulthood. The results support previous findings that variables associated with the metabolic syndrome track moderately well from adolescence to adulthood. The findings support the prevention and treatment of obesity, atherosclerosis, type 2 diabetes, and the metabolic syndrome during childhood and adolescence.     

Melanosomes and MHC class II antigen-processing compartments

Melanosomes are specialized intracellular compartments within melanocytes and retinal pigment epithelial cells that function in the synthesis, storage, and secretion of melanins, which are the major pigments made by mammals. The mechanisms that regulate the formation of melanosomes, and the pathways by which constituent proteins are targeted to them, are related to those involved in the biogenesis of major histocompatibility complex (MHC) class II antigen-processing compartments. Consequently, diseases that affect pigmentation may also affect antigen presentation to T cells. Moreover, many of the tissue-specific proteins that localize to melanosomes and participate in melanin formation double as tumor-associated antigens that are targets for T cells in patients with melanoma. Our studies on melanosome biogenesis are providing new ways of thinking about antigen-processing compartments and the mechanisms regulating presentation of tumor-associated antigens.     

Data clustering and other archive retrieval strategies for teleradiology and picture archiving and communication systems

A key advantage in the conversion from film-based to digital radiology is the possibility of a long-term on line electronic archival of patient studies. The popular approach based on optical disk jukeboxes for the long-term archive and magnetic disk storage for data caching is not economically attractive because of the cost of both the jukebox and the medium. Strategies for extending the archival system design with a tape jukebox have been studied. The proposed strategy calls for the use of high-ratio lossy compression together with low-cost tape storage to make long-term on line archiving more affordable. An intelligent prefetching algorithm based on hospital information system and radiologic information system triggers, which in turn are augmented by manual case preparation, can effectively overcome the longer latency of ad hoc retrievals. This longer latency is caused by both system-level bottlenecks and the sequential access constraint of the tape drive. Strategies for image clustering and tape allocation by patient classification also enhance retrieval efficiency. This archival design using image compression, prefetching, and clustering could be implemented in many of the existing teleradiology and picture archiving and communication systems.     

Involvement of central amygdalar and bed nucleus of the stria terminalis corticotropin-releasing factor in behavioral responses to social defeat

The authors investigated whether corticotropin-releasing factor (CRF) within the central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST) is a critical component of the neural circuitry mediating conditioned defeat. In this model, hamsters that have experienced social defeat subsequently display only submissive-defensive agonistic behavior instead of territorial aggression. Conditioned defeat was significantly reduced following infusion of the CRF receptor antagonist D-Phe CRF((12-41)) into the BNST but not into the CeA. In another experiment, hamsters given unilateral lesions of the CeA and infusions of D-Phe CRF((12-41)) into the contralateral BNST displayed significantly less submissive behavior than did controls. These data suggest that CRF acts within a neural circuit that includes the amygdala and the BNST to modulate agonistic behavior following social defeat.     

Analysis of Connective Tissue Progenitor Cell Behavior on Polydimethylsiloxane Smooth and Channel Micro-Textures

Growth of human connective tissue progenitor cells (CTPs) was characterized on smooth and microtextured polydimethylsiloxane (PDMS) surfaces. Human bone marrow derived cells were cultured for nine days under conditions promoting osteoblastic differentiation on Smooth PDMS and PDMS Channel microtextures (11 m high, 45 m wide channels, and separated by 5 m wide ridges). Glass tissue culture dish surfaces were used as controls. Cell numbers per colony, cell density within colonies, alignment of cells, area of colonies, and colony shapes were determined as a function of substrate surface topography. An alkaline phosphatase stain was used as a marker for osteoblastic phenotype. CTPs attached, proliferated, and differentiated on all surfaces with cell process lengths of up to 80 m. Cells on the Smooth PDMS and control surfaces spread and proliferated as colonies in proximity to other cells and migrated in random directions creating colonies that covered significantly larger areas (0.96 and 1.05 mm², respectively) than colonies formed on PDMS Channel textures (0.64 mm²). In contrast, cells on PDMS Channel textures spread, proliferated, aligned along the channel axis, and created colonies that were more dense, and with lengths of longest colony axes that were significantly longer (3252 m) than those on the Smooth PDMS (1265 m) and control surfaces (1319 m). Cells on PDMS Channel textures were aligned at an angle of 14.44° relative to the channel axis, and the resulting colonies exhibited a significantly higher aspect ratio (13.72) compared to Smooth PDMS (1.57) and control surfaces (1.51).     

Use and abuse of frozen section in the diagnosis of follicular thyroid lesions

The role of intraoperative frozen section in certain organ systems such as the thyroid continues to be problematic. In many cases, diagnoses are deferred or nonhelpful—“follicular lesion.” In the modern era, the widespread use of preoperative aspiration biopsy has allowed for more careful selection of patients who undergo thyroid surgery. In many cases, the fine-needle-aspiration (FNA) biopsy diagnosis can be definitive or can guide the specific surgical procedure. The literature supports our approach, which is summarized as follows: Intraoperative consultation is not needed on the intrathyroidal nodule if a preoperative FNA was definitive for papillary carcinoma. Frozen section is of no value in the intraoperative diagnosis of lesions diagnosed on FNA as “follicular neoplasm” or “Hürthle cell neoplasm” because the characterization of these lesions requires detailed analysis of the tumor capsule for the demonstration of capsular and/or vascular invasion—an analysis that is not practical in the intraoperative setting. Finally, intraoperative consultation including frozen section and intraoperative cytologic examination is most useful in those cases that are diagnosed as suspicious for papillary carcinoma by FNA, because the assessment of nuclear features needed for the definitive diagnosis is possible with intraoperative techniques in a significant number of cases.     

TCRγδ cells: Mysterious cells of the immune system

γδ cells participate in pathogenic infections and autoimmune conditions, yet, almost a decade after their discovery, little is known regarding their TCR repertoire or effector functions. Unlike MHC-restricted antigen recognition employed by TCRαβ cells, TCRγδ cells can recognize whole unprocessed antigens in an MHC-independent manner. The nature of positive and negative selection used to shape the repertoire of TCRγδ cells is unclear, especially in the nonlymphoid tissues where these cells predominate. While TCRγδ cells express an activated phenotype and are present in pathological conditions, their roles in immunological protection is unknown. This review will focus on our efforts to study these issues of TCRγδ biology.     

Ex vivo expansion and prophylactic infusion of CMV-pp65 peptide-specific cytotoxic T-lymphocytes following allogeneic hematopoietic stem cell transplantation.

Cytomegalovirus reactivation and infection post-allogeneic hematopoietic stem cell transplant continue to cause morbidity and mortality. Current pharmacologic therapies are limited by side effects. Adoptive transfer of ex vivo generated cytomegalovirus-specific T cells has the potential to restore immunity, prevent cytomegalovirus, and circumvent the need for pharmacologic therapies. We have generated donor-derived cytomegalovirus-specific cytotoxic T cells using dendritic cells pulsed with the HLA-A2 restricted nonapeptide NLVPMVATV (NLV) derived from the cytomegalovirus-pp65 protein. These cytotoxic T cells have been given prophylactically to 9 recipients aged 4 to 65 years on or after day 28 post-allogeneic hematopoietic stem cell transplant. Only 2 of 9 recipients received T cell depletion in vivo or in vitro. There were no immediate adverse reactions to the infusions. During 97-798 days of follow-up, 2 recipients developed cytomegalovirus reactivation; neither developed cytomegalovirus disease or required pharmacotherapy. Three recipients developed acute graft versus host disease after infusion. Two recipients died, 1 from thrombotic thrombocytopenia purpura secondary to cyclosporine, 1 from complications of graft versus host disease. A transient increase in numbers of cytomegalovirus-specific T cells demonstrated by NLV-tetramer binding was seen in 6 recipients. Prophylactic adoptive transfer of NLV-specific T cells is safe and may be effective in preventing cytomegalovirus reactivation.