Identification and characterization of variants in the 5' flanking region of bovine growth hormone gene

Sequence variations within the 5' flanking region of bovine growth hormone gene were identified from six bovine species raised in China. Cloned and sequenced amplified fragments revealed difference in length because of the insertion and deletion mutation. A total of thirty one variation sites were identified in this region within species and among species. Several new single nucleotide polymorphisms (SNPs) within bovine species were detected in the 5' flanking region with exception in swamp buffalo. Some important regulatory elements such as TATA box, CRE, NRE3, dPit1 and pPit1 were identified in the 5' flanking in six bovine species. The conservation of regulatory elements may be consistent with functional constraint during the course of evolution.Key words: Bovine species, growth hormone gene, variation, regulatory element

A Novel Definition of Equivalent Uniform Dose Based on Volume Dose Curve

© 2013 IEEE. With the improvement of mobile device performance, the requirement of equivalent dose description in intensity-modulated radiation therapy is increasing in mobile multimedia for healthcare. The emergence of mobile cloud computing will provide cloud servers and storage for intensity-modulated radiotherapy (IMRT) mobile applications, thus realizing visualized radiotherapy in a real sense. Equivalent uniform dose (EUD) is a biomedical indicator based on the dose measure. In this paper, the dose volume histogram is used to describe the dose distribution of different tissues in target and nontarget regions. The traditional definition of EUD, such as the exponential form and the linear form, has only a few parameters in the model for fast calculation. However, there is no close relationship between this traditional definition and the dose volume histogram. In order to establish the consistency between the EUD and the dose volume histogram, this paper proposes a novel definition of EUD based on the volume dose curve, called VD-EUD. By using a unique organic volume weight curve, it is easy to calculate VD-EUD for different dose distributions. In definition, different weight curves are used to represent the biological effects of different organs. For the target area, we should be more careful about those voxels with a low dose (cold point); thus, the weight curve is monotonically decreasing. While for the nontarget area, the curve is monotonically increasing. Furthermore, we present the curves for parallel, serial, and mixed organs of nontarget areas separately, and we define the weight curve form with only two parameters. Medical doctors can adjust the curve interactively according to different patients and organs. We also propose a fluence map optimization model with the VD-EUD constraint, which means that the proposed EUD constraint will lead to a large feasible solution space. We compare the generalized EUD (gEUD) and the proposed VD-EUD by experiments, which show that the VD-EUD has a closer relationship with the dose volume histogram. If the biological survival probability is equivalent to the VD-EUD, the feasible solution space would be large, and the target areas can be covered. By establishing a personalized organic weight curve, medical doctors can have a unique VD-EUD for each patient. By using the flexible and adjustable EUD definition, we can establish the VD-EUD-based fluence map optimization model, which will lead to a larger solution space than the traditional dose volume constraint-based model. The VD-EUD is a new definition; thus, we need more clinical testing and verification

Relationship between intact HIV-1 proviruses in circulating CD4+ T cells and rebound viruses emerging during treatment interruption.

Combination antiretroviral therapy controls but does not cure HIV-1 infection because a small fraction of cells harbor latent viruses that can produce rebound viremia when therapy is interrupted. The circulating latent virus reservoir has been documented by a variety of methods, most prominently by viral outgrowth assays (VOAs) in which CD4+ T cells are activated to produce virus in vitro, or more recently by amplifying proviral near full-length (NFL) sequences from DNA. Analysis of samples obtained in clinical studies in which individuals underwent analytical treatment interruption (ATI), showed little if any overlap between circulating latent viruses obtained from outgrowth cultures and rebound viruses from plasma. To determine whether intact proviruses amplified from DNA are more closely related to rebound viruses than those obtained from VOAs, we assayed 12 individuals who underwent ATI after infusion of a combination of two monoclonal anti-HIV-1 antibodies. A total of 435 intact proviruses obtained by NFL sequencing were compared with 650 latent viruses from VOAs and 246 plasma rebound viruses. Although, intact NFL and outgrowth culture sequences showed similar levels of stability and diversity with 39% overlap, the size of the reservoir estimated from NFL sequencing was larger than and did not correlate with VOAs. Finally, intact proviruses documented by NFL sequencing showed no sequence overlap with rebound viruses; however, they appear to contribute to recombinant viruses found in plasma during rebound

Characterization of Intact Proviruses in Blood and Lymph Node from HIV-Infected Individuals Undergoing Analytical Treatment Interruption.

The role of lymphoid tissue as a potential source of HIV-1 rebound following interruption of antiretroviral therapy (ART) is uncertain. To address this issue, we compared the latent viruses obtained from CD4+ T cells in peripheral blood and lymph nodes to viruses emerging during treatment interruption. Latent viruses were characterized by sequencing near-full-length (NFL) proviral DNA and env from viral outgrowth assays (VOAs). Five HIV-1-infected individuals on ART were studied, four of whom participated in a clinical trial of a TLR9 agonist that included an analytical treatment interruption. We found that 98% of intact or replication-competent clonal sequences overlapped between blood and lymph node. In contrast, there was no overlap between 205 latent reservoir and 125 rebound sequences in the four individuals who underwent treatment interruption. However, rebound viruses could be accounted for by recombination. The data suggest that CD4+ T cells carrying latent viruses circulate between blood and lymphoid tissues in individuals on ART and support the idea that recombination may play a role in the emergence of rebound viremia.IMPORTANCE HIV-1 persists as a latent infection in CD4+ T cells that can be found in lymphoid tissues in infected individuals during ART. However, the importance of this tissue reservoir and its contribution to viral rebound upon ART interruption are not clear. In this study, we sought to compare latent HIV-1 from blood and lymph node CD4+ T cells from five HIV-1-infected individuals. Further, we analyzed the contribution of lymph node viruses to viral rebound. We observed that the frequencies of intact proviruses were the same in blood and lymph node. Moreover, expanded clones of T cells bearing identical proviruses were found in blood and lymph node. These latent reservoir sequences did not appear to be the direct origin of rebound virus. Instead, latent proviruses were found to contribute to the rebound compartment by recombination

Eccrine porocarcinoma of the head: An important differential diagnosis in the elderly patient

Background: Eccrine porocarcinoma is a rare malignant tumor of the sweat gland, characterized by a broad spectrum of clinicopathologic presentations. Surprisingly, unlike its benign counterpart eccrine poroma, eccrine porocarcinoma is seldom found in areas with a high density of eccrine sweat glands, like the palms or soles. Instead, eccrine porocarcinoma frequently occurs on the lower extremities, trunk and abdomen, but also on the head, resembling various other skin tumors, as illustrated in the patients described herein. Observations: We report 5 cases of eccrine porocarcinoma of the head. All patients were initially diagnosed as having epidermal or melanocytic skin tumors. Only after histopathologic examination were they classified as eccrine porocarcinoma, showing features of epithelial tumors with abortive ductal differentiation. Characteristic clinical, histopathologic and immunohistochemical findings of eccrine porocarcinomas are illustrated. Conclusion: Eccrine porocarcinomas are potentially fatal adnexal malignancies, in which extensive metastatic dissemination may occur. Porocarcinomas are commonly overlooked, or misinterpreted as squamous or basal cell carcinomas as well as other common malignant and even benign skin tumors. Knowledge of the clinical pattern and histologic findings, therefore, is crucial for an early therapeutic intervention, which can reduce the risk of tumor recurrence and serious complications. Copyright (c) 2008 S. Karger AG, Basel

Relationship between latent and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117.

A clinical trial was performed to evaluate 3BNC117, a potent anti-HIV-1 antibody, in infected individuals during suppressive antiretroviral therapy and subsequent analytical treatment interruption (ATI). The circulating reservoir was evaluated by quantitative and qualitative viral outgrowth assay (Q2VOA) at entry and after 6 mo. There were no significant quantitative changes in the size of the reservoir before ATI, and the composition of circulating reservoir clones varied in a manner that did not correlate with 3BNC117 sensitivity. 3BNC117 binding site amino acid variants found in rebound viruses preexisted in the latent reservoir. However, only 3 of 217 rebound viruses were identical to 868 latent viruses isolated by Q2VOA and near full-length sequencing. Instead, 63% of the rebound viruses appeared to be recombinants, even in individuals with 3BNC117-resistant reservoir viruses. In conclusion, viruses emerging during ATI in individuals treated with 3BNC117 are not the dominant species found in the circulating latent reservoir, but frequently appear to represent recombinants of latent viruses