Immune compromise in HIV-1/HTLV-1 coinfection with paradoxical resolution of CD4 lymphocytosis during antiretroviral therapy: a case report

Human immunodeficiency virus type-1 (HIV-1) and human T lymphotropic virus type-1 (HTLV-1) infections have complex effects on adaptive immunity, with specific tropism for, but contrasting effects on, CD4 T lymphocytes: depletion with HIV-1, proliferation with HTLV-1. Impaired T lymphocyte function occurs early in HIV-1 infection but opportunistic infections (OIs) rarely occur in the absence of CD4 lymphopenia. In the unusual case where a HIV-1 infected individual with a high CD4 count presents with recurrent OIs, a clinician is faced with the possibility of a second underlying comorbidity. We present a case of pseudo-adult T cell leukemia/lymphoma (ATLL) in HIV-1/HTLV-1 coinfection where the individual fulfilled Shimoyama criteria for chronic ATLL and had pulmonary Mycobacterium kansasii, despite a high CD4 lymphocyte count. However, there was no evidence of clonal T-cell proliferation by T-cell receptor gene rearrangement studies nor of monoclonal HTLV-1 integration by high-throughput sequencing. Mutually beneficial interplay between HIV-1 and HTLV-1, maintaining high level HIV-1 and HTLV-1 viremia and proliferation of poorly functional CD4 cells despite chronicity of infection is a postulated mechanism. Despite good microbiological response to antimycobacterial therapy, the patient remained systemically unwell with refractory anemia. Subsequent initiation of combined antiretroviral therapy led to paradoxical resolution of CD4 T lymphocytosis as well as HIV-1 viral suppression and decreased HTLV-1 proviral load. This is proposed to be the result of attenuation of immune activation post-HIV virological control. This case illustrates the importance of screening for HTLV-1 in HIV-1 patients with appropriate clinical presentation and epidemiological risk factors and explores mechanisms for the complex interactions on HIV-1/HTLV-1 adaptive immunity

Adult T-cell leukemia/lymphoma—pathobiology and implications for modern clinical management

Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive malignancy that arises in 2-5% of carriers of human T-cell lymphotropic virus type 1 (HTLV-1). The median overall survival of acute and lymphoma subtypes remains approximately 9–13 months and depressingly, with chemotherapy based approaches survival is largely unchanged in the ~40 years since it was first described. There is a clear and urgent need to conduct clinical trials of novel therapies in this disease. A high proviral load (PVL) (>4%, percentage of HTLV-1 infected mononuclear cells), male gender and smoking were previously the only major known risk factors for developing ATL, and so it has been difficult to advise patients about their individual risk of future ATL. Here, we describe the recent evidence that malignant disease does not occur randomly amongst all asymptomatic carriers but is more likely to arise in a subset of high PVL individuals with abnormally abundant clonal expansions of circulating HTLV-1 infected T-cells which typically express CD3dim+ CD4+ CD5-CD7- CD25+ CCR4+ with monoclonal TCRVβ. These clones also typically harbour known ATL driver mutations such as PLCG1, PRKCB, CARD11, STAT3, VAV1, NOTCH1, IRF4, CCR4, CCR7, TP53 and CDKN2, and may be detectable 10 years prior to disease presentation providing an opportunity to identify at risk individuals prior to clinical ATL. We describe the current classification and clinical features of ATL, and the exciting work of the last few years that underpins our new understanding of the genetic and epigenetic landscape with implications for future therapy. Whilst current therapy for aggressive ATL remain largely ineffective, recent advances may allow for early identification of at-risk individuals, and for pre-emptive therapies, and hope for a new era of effective targeted biological agents

The Formation and Properties of Thin Lipid Membranes from HK and LK Sheep Red Cell Lipids

Lipids were obtained from high potassium (HK) and low potassium (LK) sheep red cells by sequential extraction of the erythrocytes with isopropanol-chloroform, chloroform-methanol-0.1 M KCl, and chloroform. The extract contained cholesterol and phospholipid in a molar ratio of 0.8:1.0, and less than 1% protein contaminant. Stable thin lipid membranes separating two aqueous compartments were formed from an erythrocyte lipid-hydrocarbon solution, and had an electrical resistance of ∼108 ohm-cm2 and a capacitance of 0.38–0.4 µf/cm2. From the capacitance values, membrane thickness was estimated to be 46–132 A, depending on the assumed value for the dielectric constant (2.0–4.5). Membrane voltage was recorded in the presence of ionic (NaCl and/or KCl) concentration gradients in the solutions bathing the membrane. The permeability of the membrane to Na+, K+, and Cl- (expressed as the transference number, Tion) was computed from the steady-state membrane voltage and the activity ratio of the ions in the compartments bathing the membrane. TNa and TK were approximately equal (∼0.8) and considerably greater than TCl (∼0.2). The ionic transference numbers were independent of temperature, the hydrocarbon solvent, the osmolarity of the solutions bathing the membranes, and the cholesterol content of the membranes, over the range 21–38°C. The high degree of membrane cation selectivity was tentatively attributed to the negatively charged phospholipids (phosphatidylethanolamine and phosphatidylserine) present in the lipid extract

Influence of Elastic Strains on the Adsorption Process in Porous Materials. An Experimental Approach

The experimental results presented in this paper show the influence of the elastic deformation of porous solids on the adsorption process. With p+-type porous silicon formed on highly boron doped (100) Si single crystal, we can make identical porous layers, either supported by or detached from the substrate. The pores are perpendicular to the substrate. The adsorption isotherms corresponding to these two layers are distinct. In the region preceding capillary condensation, the adsorbed amount is lower for the membrane than for the supported layer and the hysteresis loop is observed at higher pressure. We attribute this phenomenon to different elastic strains undergone by the two layers during the adsorption process. For the supported layer, the planes perpendicular to the substrate are constrained to have the same interatomic spacing as that of the substrate so that the elastic deformation is unilateral, at an atomic scale, and along the pore axis. When the substrate is removed, tridimensional deformations occur and the porous system can find a new configuration for the solid atoms which decreases the free energy of the system adsorbate-solid. This results in a decrease of the adsorbed amount and in an increase of the condensation pressure. The isotherms for the supported porous layers shift toward that of the membrane when the layer thickness is increased from 30 to 100 microns. This is due to the relaxation of the stress exerted by the substrate as a result of the breaking of Si-Si bonds at the interface between the substrate and the porous layer. The membrane is the relaxed state of the supported layer.Comment: Accepted in Langmui

Drying Shrinkage Mechanisms in Portland Cement Paste

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65426/1/j.1151-2916.1987.tb05002.x.pd