Human papillomavirus was not detected by PCR using multiple consensus primer sets in esophageal adenocarcinomas in Chinese patients

The role of human papillomavirus (HPV) infection in the development of esophageal squamous cell carcinoma is well established; however, there are few reports on the role of HPV in esophageal adenocarcinoma. To evaluate the putative role of HPV infection in esophageal adenocarcinoma, 57 formalin‐fixed, paraffin‐embedded esophageal adenocarcinoma specimens were collected from four hospitals in Shanghai and Anyang, China, between 1999 and 2008. HPV DNA was analyzed using PCR with multiple sets of consensus primers for HPV, GP5+/6+, CPI/CPIIG, SPF₁₀, pU‐1M/pU2R, and pU31B/pU2R. Glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), the internal control, was amplified successfully in all 57 specimens. However, HPV amplification was not detected in any specimens with any of the consensus primer sets used. The present study indicates that HPV infection is not likely to be a major factor in the etiology of esophageal adenocarcinoma in the Chinese population. J. Med. Virol. 85: 1053–1057, 2013. © 2013 Wiley Periodicals, Inc.     

Activation of Toll-like receptor 2 increases macrophage resistance to HIV-1 infection

Patients infected with HIV-1, the etiological agent of AIDS, have increased intestinal permeability, which allows for the passage of microbial products, including Toll-like receptor (TLR) ligands, into circulation. The exposure of HIV-1-infected cells to certain TLR agonists affects viral replication, but studies associating viral production with the activation of TLR2 in HIV-1-infected cells are rare and controversial. Here, we report that the TLR2 ligands Zymosan and Pam3CSK4 potently inhibit HIV-1 replication in acutely infected monocyte-derived macrophages and the exposure to TLR2 ligands prior to infection renders macrophages refractory to HIV-1 production. Macrophage treatment with Pam3CSK4 did not change the cellular expression of the HIV-1 entry receptors CD4 and CCR5. Both TLR2 ligands increased the macrophage production of β-chemokines and IL-10, and the blockage of these soluble factors prevented the inhibitory effect of TLR2 activation on HIV-1 replication. Our findings show that the direct engagement of TLR2 in HIV-1-infected macrophages increase cellular resistance to HIV-1 infection, and that controlling HIV-1 replication with agonists for TLR2 might have implications for the development of antiretroviral therapies.     

Effects of Pulsed Electromagnetic Fields on Human Articular Chondrocyte Proliferation

Low-energy, low-frequency pulsed electromagnetic fields (PEMFs) can induce cell proliferation in several cell culture models. In this work we analysed the proliferative response of human articular chondrocytes, cultured in medium containing 10% FBS, following prolonged exposure to PEMFs (75 Hz, 2.3 mT), currently used in the treatment of some orthopaedic pathologies. In particular, we investigated the dependence of the proliferative effects on the cell density, the availability of growth factors and the exposure lengths. We observed that PEMFs can induce cell proliferation of low density chondrocyte cultures for a long time (6 days), when fresh serum is added again in the culture medium. In the same conditions, in high density cultures, the PEMF-induced increase in cell proliferation was observed only in the first three days of exposure. The data presented in this study show that the availability of growth factors and the environmental constrictions strongly condition the cellular proliferative response to PEMFs.     

Tissue transglutaminase autoantibodies in children with newly diagnosed type 1 diabetes are related to human leukocyte antigen but not to islet autoantibodies: A Swedish nationwide prospective population-based cohort study

Abstract

Objectives: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D).

Patients and methods: Dried blood spots and serum samples were taken at diagnosis from children <18?years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA).

Results: Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p?=?.00001) and those with DQX/X (p?≤?.00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p?=?.018).

Conclusion: tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD.     

Understanding HIV-Related Pill Aversion as a Distinct Barrier to Medication Adherence

Abstract

Pill aversion, defined as difficulty swallowing pills without identifiable medical cause, is a poorly characterized barrier to sustained viral suppression for many HIV-infected persons. We aimed to quantify the frequency of self-reported pill aversion, characterize its symptoms, and measure the association between self-reported pill aversion and missing antiretroviral doses. This is a prospective, observational, exploratory survey study of English-speaking persons living with HIV (PLHIV) at a single urban tertiary outpatient clinic. Participants completed anonymous questionnaires about their experiences of swallowing antiretroviral pills. The primary outcome was skipping pills due to pill aversion symptoms. Of 384 participants, a quarter (25.5%) skipped pills due to pill aversion symptoms. Younger age, being Non-Hispanic Black or Hispanic, not being married or partnered, having public insurance, not being employed, having less than a college education, and having a mental health diagnosis were associated with skipping pills due to pill aversion. On multivariable regression analyses, PLHIV who skipped pills were more likely to report symptoms of gagging, nausea at the time of swallowing, and heavy feeling in the stomach, as well as being bothered by the taste, smell, and size of the pills. PLHIV who skipped pills were also more likely to report negative and fear-based emotions about pill-taking than PLHIV who did not skip pills due to pill aversion. HIV-related pill aversion may represent a significant and frequent barrier to adherence in an adult HIV population.     

Potential involvement of BMP receptor type IB activation in a synergistic effect of chondrogenic promotion between rhTGFβ3 and rhGDF5 or rhBMP7 in human mesenchymal stem cells

Chondrogenic promotion by rhGDF5 with or without rhTGFβ3 was studied in pellet culture of human mesenchymal stem cells (HMSCs). A synergy between rhGDF5 and rhTGFβ3 was observed in promoting chondrogenesis. rhBMP2, rhBMP6, rhBMP7 and rhTGFβ1 were further tested and showed the same effect. To explore the mechanism, the expression of TGFβtype I and II receptors, ALK5, ALK2, ALK3, ALK6, TGFβRII, BMPRII, ActRII was studied. ALK6 showed increase by the rhTGFβ1 or rhTGFβ3 treatment. ALK6 protein expression also showed increase by rhTGFβ3. rhTGFβ1/rhTGFβ3 induced ALK6 up-regulation was inhibited by SD-208, a TGFβ type I receptor inhibitor. Chondrogenesis by rhTGFβ1/rhTGFβ3 or the combination between rhTGFβ1/rhTGFβ3 and rhGDF5 also was diminished by SD-208. SMAD1/5/8 phosphorylation in nascent human mesenchymal stem cells (HMSCs) was stimulated weakly by rhGDF5 but strongly by rhBMP7. The rhGDF5 stimulated SMAD1/5/8 phosphorylation was enhanced by rhTGFβ1/rhTGFβ3 but inhibited by SD-208. The rhBMP7 stimulated SMAD1/5/8 phosphorylation did not show influence by rhTGFβ3 and SD-208. Our results indicated the potential involvement of ALK6 activation by rhTGFβs in the synergy between rhTGFβs and rhBMPs.     

Effects of environmental parameters and composition of poly(2-hydroxyethyl methacrylate)-graft-polyamine copolymers on the retention of rat lymphocyte subpopulations (B- and T-cells)

Retention behavior of rat lymphocyte subpopulations (B- and T-cells) was investigated on poly(2-hydroxyethyl methacrylate)-graft-polyamine (HA) copolymers with various copolymer compositions. Separation mechanism of B- and T-cells was then evaluated by focusing on several parameters, such as pH, temperature, and ionic strength. The interaction of lymphocytes with HA surfaces was mainly through the electrostatic force from their retention profile at varying ionic strengths of the medium. Temperature also has a crucial effect on the response of lymphocytes toward pH-induced phase transition of polyamine grafts at the polymer interface with aqueous milieu. At 4°C, both B- and T-cells showed minimal retention on HA surfaces at pH 8. At this pH, polyamine grafts existed in a compact conformation with a low degree of protonation. However, at pHs below 8, at which polyamine grafts existed in extended conformation, the resolution of B- and T-cells was achieved. In contrast, at 23°C, the phase transition of polyamine grafts significantly influenced T-cell retention, resulting in a decrease in the retention of T-cells on HA with polyamine in a compact conformation. Consequently, preferential retention of B-cells was achieved under this condition. The polyamine content was found to be another important factor affecting the retention behavior of lymphocyte subpopulations. On HA copolymers with low polyamine content (HA7, HA10), conformational transition of polyamine grafts showed a significant influence for B-cell retention, although the influence decreased with increasing polyamine content. From the study estimating the effect of neuraminidase treatment of lymphocytes on their retention to HA surfaces, sialic acid residues on the plasma membrane surface of lymphocytes are suggested as feasible anionic sites showing electrostatic interaction with polyamine grafts.     

Patients treated with high‐dose intravenous immunoglobulin show selective activation of regulatory T cells

Intravenous immunoglobulin (IVIg) is used to treat autoimmune and systemic inflammatory diseases caused by derailment of humoral and cellular immunity. In this study we investigated whether IVIg treatment can modulate regulatory T cells (T_regs) in humans in vivo. Blood was collected from IVIg-treated patients with immunodeficiency or autoimmune disease who were treated with low-dose (n = 12) or high-dose (n = 15) IVIg before, immediately after and at 7 days after treatment. Percentages and activation status of circulating CD4⁺CD25⁺forkhead box protein 3 (FoxP3⁺) T_regs and of conventional CD4⁺FoxP3⁻ T-helper cells (T_conv) were measured. The suppressive capacity of T_regs purified from blood collected at the time-points indicated was determined in an ex-vivo assay. High-dose, but not low-dose, IVIg treatment enhanced the activation status of circulating T_regs, as shown by increased FoxP3 and human leucocyte antigen D-related (HLA-DR) expression, while numbers of circulating T_regs remained unchanged. The enhanced activation was sustained for at least 7 days after infusion, and the suppressive capacity of purified T_regs was increased from 41 to 70% at day 7 after IVIg treatment. The activation status of T_conv was not affected by IVIg. We conclude that high-dose IVIg treatment activates T_regs selectively and enhances their suppressive function in humans in vivo. This effect may be one of the mechanisms by which IVIg restores imbalanced immune homeostasis in patients with autoimmune and systemic inflammatory disorders.