The multiple drug resistance gene,MDR1: Expression at the protein and RNA levels

A comparison of three different approaches to detect MDR₁ expression in myeloid leukemia cells was undertaken. With respect to the 4 different antibodies studied, a high proportion of false positive reactions were detected. Substantial discordance between MDR₁ expression as indicated by Northern blot analysis, PCR, and immunohistochemistry was found. These findings complicate the clinical interpretation of data derived from these methods.     

No evidence for humoral autoimmunity against cardiomyocytes,adrenergic or muscarinic receptors in patients with Tako-Tsubo cardiomyopathy

Background

An association between Tako-Tsubo cardiomyopathy (TTC) and underlying malignancies has been observed, suggesting that TTC might be the consequence of paraneoplastic phenomena. This study investigates the presence of autoantibodies against cardiomyocytes as well as adrenergic (β₁, β₂) and muscarinic (M2) receptors in patients with TTC.

Human interleukin 7 is a B cell growth factor for activated B cells

We investigated the capacity of human interleukin (IL) 7 to induce proliferation of B cells. Purified tonsillar B cells were cultured in the presence of IL7 with Staphylococcus aureus Cowan I (SAC) or anti-μ beads as co-mitogens. IL 7 supported a dose-dependent proliferation of anti-μ-activated B cells but did not significantly support proliferation of SAC-activated B cells. When B cells were separated on Percoll gradient into small (60%-80%) and large (50%–60%) B cells and then cultured with anti-μ beads, IL7 acted on both cell populations equally well. IL7 and BCGF (low molecular weight) were synergistic in their proliferative action on anti-μ-activated B cells in a 5-day culture. On the other hand, synergistic effect of IL 7 on activated B cells was not evident in the presence of any other factor recombinant [(r)IL 1β, rIL2, rIL3, rIL4, rIL5, rIL6, recombinant tumor necrosis factor-α, recombinant lymphotoxin, recombinant granulocyte-monocyte colony-stimulating factor and recombinant interferon-γ] we tested. IL7 did not induce IgG secretion by activated B cells.     

Safety,tolerability, and effectiveness of oral zonisamide therapy in comparison with intramuscular adrenocorticotropic hormone therapy in infants with West syndrome

West syndrome is a distinct, infantile onset, epileptic encephalopathy, associated with poor neurodevelopmental outcome. The present study was designed as a randomized, open-label, pilot study to evaluate the safety, feasibility, and effectiveness of oral zonisamide therapy in comparison with adrenocorticotropic hormone therapy in infants with West syndrome. Thirty infants with West syndrome were randomized to receive treatment with either synthetic, intramuscular adrenocorticotropic hormone (30–60 IU) or oral zonisamide (4–25 mg/kg/day). The study participants had a long treatment lag and preponderance of male sex (90%). The primary effectiveness outcome measure was the cessation of epileptic spasms at 2 weeks of initiation of therapy and persistent till 6 weeks as per West Delphi consensus statement recommendations. Comparison of efficacies of zonisamide versus adrenocorticotropic hormone was as following: the cessation of epileptic spasms (27% vs. 40%, p = 0.70), resolution of hypsarrhythmia at 14 days (20% vs. 33%, p = 0.68) and resolution of hypsarrhythmia at 6 weeks (36% vs. 71%, p = 0.14). Overall, the study observed a poor efficacy of both adrenocorticotropic hormone and zonisamide therapy, which is probably due to long treatment lag and a high proportion of structural aetiology. However, oral zonisamide appeared to be safe and tolerable in the study.     

Role of IL-10 -819(T/C) Promoter Polymorphism in Preeclampsia

—Preeclampsia is a severe complication of pregnancy characterized by an excessive maternal systemic inflammatory response with activation of both the innate and adaptive immune system. Interleukin-10 affects maternal intravascular inflammation, as well as endothelial dysfunction. The aim of the study was to investigate the association between IL-10 T-819 C polymorphism and preeclampsia. A total of 120 pregnant women with preeclampsia and 120 women with normal pregnancy attending the Gynecological Unit of Government Maternity Hospital, Petlaburz, Hyderabad, India, were considered for the present study. A standard amplification refractory mutation system (ARMS) PCR was carried out for genotyping of IL-10 T-819 C promoter polymorphism in all the participants. Genotypic distribution of the control and patient groups was compared with values predicted by the Hardy-Weinberg equilibrium using χ2 test. Odds ratios (OR) and their respective 95 % confidence intervals were used to measure the strength of association between IL-10 gene polymorphism and preeclampsia. The frequencies of IL-10 T-819 C genotypes, CC, CT, and TT, were 47.5, 28.3, and 24.2 % in women with preeclampsia and 20.8, 48.3, and 30.8 % in the controls, respectively. There is a significant difference in the distribution of genotypes and alleles of IL-10 T-819 C between the two groups (test power?=?0.66). The present study suggests that the IL-10 T-819 C gene promoter polymorphism can be a major genetic regulator in the etiology of preeclampsia     

Haplotype analysis of IL-10 gene polymorphism in couples with spontaneous abortions and aborted fetuses

Spontaneous abortion is the loss of pregnancy during an early gestational period. Interleukin-10 is an anti-inflammatory cytokine which plays an important role in successful pregnancy outcome. The aim of the study is to elucidate an association of IL-10 gene promoter polymorphisms (-1082G/A, -819 C/T, -592C/A) in spontaneous abortions from Telangana state of South India. The present population-based retrospective case-control triad study includes a total of 80 case families with spontaneous abortions and 100 control families with medically terminated pregnancies. Peripheral blood from all the couples and fetal tissues of <20 weeks of gestation were collected. Genotype analysis was carried out by a standard amplification refractory mutation system–polymerase chain reaction followed by agarose gel electrophoresis. The strength of the association between IL-10 gene promoter polymorphisms and spontaneous abortions were measured by odd ratios and their respective 95% confidence intervals. Haplotype analysis was carried out for the three polymorphisms to establish an association of specific haplotypes with spontaneous abortions. The increased frequency of AA genotype and A allele of -1082G/A, TT genotype and T allele of -819C/T, and AA genotype and A allele of -592C/A was observed in case fetuses and case mothers compared to their respective controls. Haplotype analysis revealed that A-C-A, G-C-A haplotypes in fetuses and haplotypes A-C-C, G-T-C, A-T-A, and G-C-A in mothers were associated with increased risk of spontaneous abortions. IL-10 gene promoter polymorphisms may act as a major genetic regulator in the etiology of spontaneous abortions with maternal genome imprinting effects.     

Minocycline attenuates HIV‐1 infection and suppresses chronic immune activation in humanized NOD/LtsZ‐scidIL‐2Rγnull mice

More than a quarter of a century of research has established chronic immune activation and dysfunctional T cells as central features of chronic HIV infection and subsequent immunodeficiency. Consequently, the search for a new immunomodulatory therapy that could reduce immune activation and improve T‐cell function has been increased. However, the lack of small animal models for in vivo HIV study has hampered progress. In the current study, we have investigated a model of cord blood haematopoietic progenitor cells (CB‐HPCs) ‐transplanted humanized NOD/LtsZ‐scidIL‐2Rγ^null mice in which progression of HIV infection is associated with widespread chronic immune activation and inflammation. Indeed, HIV infection in humanized NSG mice caused up‐regulation of several T‐cell immune activation markers such as CD38, HLA‐DR, CD69 and co‐receptor CCR5. T‐cell exhaustion markers PD‐1 and CTLA‐4 were found to be significantly up‐regulated on T cells. Moreover, increased plasmatic levels of lipopolysaccharide, sCD14 and interleukin‐10 were also observed in infected mice. Treatment with minocycline resulted in a significant decrease of expression of cellular and plasma immune activation markers, inhibition of HIV replication and improved T‐cell counts in HIV‐infected humanized NSG mice. The study demonstrates that minocycline could be an effective, low‐cost adjunctive treatment to regulate chronic immune activation and replication of HIV.