Biomedical subjects

Alan Herron

Publications and source records attributed to Alan Herron.

5 recordsLinked to original sources

PubMed2006

Activating Notch1 mutations are an early event in T-cell malignancy of Ikaros point mutant Plastic/+ mice.

Ikaros and Notch1 genes are critical to T-cell differentiation through transcriptional activation of target genes and interaction with chromatin remodeling complexes. An Ikaros (Plastic) point mutation inhibits activity of normal Ikaros and Ikaros family members, and leads to T-cell lymphoma in heterozygotes (Plstc/+). Analysis revealed Notch1 activating mutations in 12 of 17 Plstc/+ lymphomas (70%), analogous to those in human T-ALL. Mice acquired Notch1 mutations in lymph nodes as early as 7 weeks. Thus, combined Notch1 and Ikaros dysfunction can be a significant early event in T-cell proliferation and tumorigenesis.

Animals↗

PubMed2006

Transcriptional repressor Blimp-1 regulates T cell homeostasis and function.

The B lymphocyte-induced maturation protein 1 (Blimp-1) transcriptional repressor is required for terminal differentiation of B lymphocytes. Here we document a function for Blimp-1 in the T cell lineage. Blimp-1-deficient thymocytes showed decreased survival and Blimp-1-deficient mice had more peripheral effector T cells. Mice lacking Blimp-1 developed severe colitis as early as 6 weeks of age, and Blimp-1-deficient regulatory T cells were defective in blocking the development of colitis. Blimp-1 mRNA expression increased substantially in response to T cell receptor stimulation. Compared with wild-type CD4(+) T cells, Blimp-1-deficient CD4(+) T cells proliferated more and produced excess interleukin 2 and interferon-gamma but reduced interleukin 10 after T cell receptor stimulation. These results emphasize a crucial function for Blimp-1 in controlling T cell homeostasis and activation.

Animals↗

PubMed2006

Visualizing pancreatic beta-cell mass with [11C]DTBZ.

Beta-cell mass (BCM) influences the total amount of insulin secreted, varies by individual and by the degree of insulin resistance, and is affected by physiologic and pathologic conditions. The islets of Langerhans, however, appear to have a reserve capacity of insulin secretion and, overall, assessments of insulin and blood glucose levels remain poor measures of BCM, beta-cell function and progression of diabetes. Thus, novel noninvasive determinations of BCM are needed to provide a quantitative endpoint for novel therapies of diabetes, islet regeneration and transplantation. Built on previous gene expression studies, we tested the hypothesis that the targeting of vesicular monoamine transporter 2 (VMAT2), which is expressed by beta cells, with [11C]dihydrotetrabenazine ([11C]DTBZ), a radioligand specific for VMAT2, and the use of positron emission tomography (PET) can provide a measure of BCM. In this report, we demonstrate decreased radioligand uptake within the pancreas of Lewis rats with streptozotocin-induced diabetes relative to their euglycemic historical controls. These studies suggest that quantitation of VMAT2 expression in beta cells with the use of [11C]DTBZ and PET represents a method for noninvasive longitudinal estimates of changes in BCM that may be useful in the study and treatment of diabetes.

Animals↗

PubMed2006

Comparison of BioGlue reinforced and standard running sutured vesicourethral anastomoses.

OBJECTIVES: To compare a BioGlue-reinforced laparoscopically sutured vesicourethral anastomosis (VUA) with a standard laparoscopically sutured VUA in a porcine model. METHODS: Twelve pigs were divided into two groups. In group 1 (n = 6), a standard laparoscopically sutured VUA was performed. In group 2 (n = 6), a standard laparoscopic sutured VUA was performed, and the anastomosis was reinforced with BioGlue. Groups 1 and 2 were completed consecutively. The animals in both groups were killed at 1 week postoperatively. In all cases, cystography was performed immediately after completion of the anastomosis and at death. At necropsy, the gross findings of the VUA were documented, and each anastomosis was excised en bloc for an extensive histopathologic evaluation of the healing parameters, including inflammation and fibrosis at each tissue level, foreign body reactions, and necrosis. RESULTS: Of the 12 VUAs, 11 were successfully performed laparoscopically. The median operative time for groups 1 and 2 was 70 and 100 minutes, respectively (P = 0.03). The median anastomotic time for groups 1 and 2 was 30 and 50 minutes, respectively (P = 0.02). No difference was seen in urinary extravasation on the cystographic evaluation in the immediate postoperative or 1-week evaluations. At necropsy, a gross complete circumferential histologic tissue approximation was noted in 1 (20%) of 5 pigs in group 1 and 2 (33%) of 6 pigs in group 2 (P = 0.66). No urinomas were noted in either group. Histopathologic evaluation revealed no significant difference between groups 1 and 2 regarding inflammation, fibrosis, foreign body reactions, or necrosis. CONCLUSIONS: The application of BioGlue to the anastomotic line extended the procedure time and did not improve the quality of the VUA.

Anastomosis, Surgical↗

PubMed2006

Current progress in non-invasive imaging of beta cell mass of the endocrine pancreas.

The increasing incidence of diabetes requires a better understanding of the pathogenesis of the clinical disease. Studies in prevention and treatment have been hampered by the single end-point of diagnosis of diabetes and hyperglycemia. The common pathology in both type 1 and type 2 diabetes is insufficient beta-cell mass to meet the metabolic demand. Unfortunately, current diagnostic methods rely on metabolic responses that do not accurately reflect true beta-cell mass. Recent advances in beta-cell imaging have utilized multiple modalities in experimental and clinical settings. While no "gold-standard" exists to measure beta-cell mass, modalities such as single photon emission computed tomography, optical and fluorescent imaging, magnetic resonance imaging, and positron emission tomography have been used with mixed success. Many of the methods are limited by the inability to translate to the clinical setting, poor discrimination between the exocrine and endocrine pancreas, or a poor measurement of beta-cell mass. However, promising new "neurofunctional imaging" approaches have emerged as improved measures of beta-cell mass. We review the current understanding of the pathogenesis and evaluation of diabetes, as well as experimental approaches to assessing beta-cell mass.

Animals↗