Transcriptionally Active Defective HIV-1 Proviruses and Their Association With Immunological Nonresponse to Antiretroviral Therapy.

A subset of antiretroviral therapy-treated persons with human immunodeficiency virus (HIV), referred to as immunological nonresponders (INRs), fails to normalize CD4+ T-cell numbers. In a case-control study involving 26 INRs (CD4 < 250 cells/µL) and 25 immunological responders (IRs; CD4 ≥ 250 cells/µL), we evaluated the potential contribution of transcriptionally competent defective HIV-1 proviruses to poor CD4+ T-cell recovery. Compared to the responders, the INRs had higher levels of cell-associated HIV RNA (P = .

Long-term persistence of transcriptionally active 'defective' HIV-1 proviruses: implications for persistent immune activation during antiretroviral therapy.

Objectives: People with HIV-1 (PWH) on effective antiretroviral therapy (ART) continue to exhibit chronic systemic inflammation, immune activation, and persistent elevations in markers of HIV-1 infection [including HIV-DNA, cell-associated HIV-RNA (CA HIV-RNA), and antibodies to HIV-1 proteins] despite prolonged suppression of plasma HIV-RNA levels less than 50 copies/ml. Here, we investigated the hypothesis that nonreplicating but transcriptionally and translationally competent 'defective' HIV-1 proviruses may be one of drivers of these phenomena.

Design: A combined cohort of 23 viremic and virologically suppressed individuals on ART were studied.

Defective HIV-1 proviruses produce viral proteins.

HIV-1 proviruses persist in the CD4 T cells of HIV-infected individuals despite years of combination antiretroviral therapy (cART) with suppression of HIV-1 RNA levels <40 copies/mL. Greater than 95% of these proviruses detected in circulating peripheral blood mononuclear cells (PBMCs) are referred to as "defective" by virtue of having large internal deletions and lethal genetic mutations. As these defective proviruses are unable to encode intact and replication-competent viruses, they have long been thought of as biologically irrelevant "graveyard" of viruses with little significance to HIV-1 pathogenesis.

Trabeculectomy Versus Ex-Press Glaucoma Filtration Device in Silicomacrophagocytic Open Angle Glaucoma Secondary to Silicone Oil Emulsification.

Purpose: To compare the outcomes of Ex-PRESS device implantation versus trabeculectomy in patients with ocular hypertension after pars plana vitrectomy and silicone oil injection (SOI).

Materials And Methods: Twenty-six consecutive eyes with ocular hypertension after pars plana vitrectomy and SOI were included in this study and randomized to one of two groups: A group treated with Ex-PRESS (model P50) placed under a scleral flap (Ex-PRESS group), and a group treated with trabeculectomy (trabeculectomy group). Complete success (intraocular pressure [IOP] <21 mmHg without medication) and qualified success rates (IOP <21 mmHg with one or two glaucoma medications) at 2 years postoperatively were analyzed.

Can Variability of Pattern ERG Signal Help to Detect Retinal Ganglion Cells Dysfunction in Glaucomatous Eyes?

Objective: To evaluate variability of steady-state pattern electroretinogram (SS-PERG) signal in normal, suspected, and glaucomatous eyes.

Methods: Twenty-one subjects with suspected glaucoma due to disc abnormalities (GS), 37 patients with early glaucoma (EG), and 24 normal control (NC) were tested with spectral-domain optical coherence tomography (SD-OCT), standard automated perimetry (SAP), and SS-PERG. Mean deviation (MD), pattern standard deviation (PSD), retinal nerve fiber layer (RNFL), and ganglionar complex cells (GCC) were evaluated.

Murine leukemia virus envelope gp70 is a shared biomarker for the high-sensitivity quantification of murine tumor burden.

The preclinical development of anticancer drugs including immunotherapeutics and targeted agents relies on the ability to detect minimal residual tumor burden as a measure of therapeutic efficacy. Real-time quantitative (qPCR) represents an exquisitely sensitive method to perform such an assessment. However, qPCR-based applications are limited by the availability of a genetic defect associated with each tumor model under investigation.

FAM190A deficiency creates a cell division defect.

Like the p16, SMAD4, and RB1 genes, FAM190A (alias CCSER1) lies at a consensus site of homogeneous genomic deletions in human cancer. FAM190A transcripts in 40% of cancers also contain in-frame deletions of evolutionarily conserved exons. Its gene function was unknown.

Trabeculectomy with double low dose of mitomycin C - two years of follow-up.

Purpose: To evaluate the efficacy and the safety of a surgical technique in which classic trabeculectomy ab externo is performed with a double application of low-dose mitomycin C (MMC) in uncontrolled open-angle glaucoma (OAG) patients.

Method: A consecutive series of 43 white patients (43 eyes) with uncontrolled primary OAG underwent trabeculectomy surgery. A double application of MMC (0.

Loss of expression of the SWI/SNF chromatin remodeling subunit BRG1/SMARCA4 is frequently observed in intraductal papillary mucinous neoplasms of the pancreas.

A better molecular characterization of intraductal papillary mucinous neoplasm (IPMN), the most frequent cystic precursor lesion of pancreatic adenocarcinoma, may have a pivotal role in its early detection and in the development of effective therapeutic strategies. BRG1, a central component of the chromatin remodeling complex SWI/SNF regulating transcription, is inactive in several malignancies. In this study, we evaluate the Brg1 expression in intraductal papillary mucinous neoplasm to better understand its role in the pancreatic carcinogenesis.

Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis.

Reactive oxygen species (ROS) are mutagenic and may thereby promote cancer. Normally, ROS levels are tightly controlled by an inducible antioxidant program that responds to cellular stressors and is predominantly regulated by the transcription factor Nrf2 (also known as Nfe2l2) and its repressor protein Keap1 (refs 2-5). In contrast to the acute physiological regulation of Nrf2, in neoplasia there is evidence for increased basal activation of Nrf2.

FAM190A rearrangements provide a multitude of individualized tumor signatures and neo-antigens in cancer.

We found FAM190A transcripts to have internal rearrangements in 40% (19/48) of unselected human cancers. Most of these tumors (84%) had in-frame structures, 94% of which involved deletion of exon 9. The FAM190A gene is located at 4q22.

A new class of dual-targeted antivirals: monophosphorylated acyclovir prodrug derivatives suppress both human immunodeficiency virus type 1 and herpes simplex virus type 2.

Background: Human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 2 (HSV-2) are responsible for 2 intersecting epidemics in which the disease caused by 1 virus facilitates the transmission of and pathogenesis by the other. Therefore, suppression of one virus infection will affect the other. Acyclovir, a common antiherpetic drug, was shown to directly suppress both viruses in coinfected tissues.

Troglitazione affects survival of human osteosarcoma cells.

Activation of PPAR gamma, a transcription factor member of the family of peroxisome proliferator-activated receptors, induces apoptosis in several normal and tumor cell lines. In our study, we investigated whether treatment with troglitazone (TRO), a known PPAR gamma agonist, induced apoptosis in the human osteosarcoma (OS) cell lines G292, MG63, SAOS and U2OS that express PPAR gamma. In our experiments, TRO never induced apoptosis of OS cells; on the contrary, TRO increased cell number, based on MTT proliferation assay.