Genetic and epigenetic alterations of the EGFR and mutually independent association with BRCA1, MGMT,and RASSF1A methylations in Vietnamese lung adenocarcinomas

Genetic and epigenetic alterations importantly contribute to the pathogenesis of lung cancer. In the study, we measured the frequency and distribution of molecular abnormalities of EGFR as well as the aberrant promoter methylations of BRCA1, MGMT, MLH1, and RASSF1A in Vietnamese lung adenocarcinomas. We investigated the association between genetic and epigenetic alteration, and between each abnormality with clinicopathologic parameters. Somatic EGFR mutation that was found in 49/139 (35.3%) lung adenocarcinomas showed a significant association with young age, female gender, and non-smokers. EGFR overexpression was identified in 82 tumors (59.0%) and statistical relationships with EGFR or BRCA1 methylation but not EGFR mutation. In addition, EGFR, BRCA1, MGMT, MLH1, and RASSF1A methylations were found in 33 (23.7%), 41 (29.5%), 46 (33.1%), 28 (20.1%), and 41 (29.5%) cases of a total of 139 lung adenocarcinomas, respectively. The RASSF1A methylation was found to be linked to the smoking habit. Methylations in MGMT and RASSF1A were also found to correlate with metastasis status. Furthermore, the distribution of EGFR mutation and that of BRCA1, MGMT or RASSF1A methylation were significantly exclusive in lung adenocarcinomas. The main finding of our study demonstrate that epigenetic abnormalities might play a critical role for the lung tumorigenesis in patients with smoking history and metastasis, and partly affect the predictive value of EGFR mutations through blocking expression due to promoter EGFR hypermethylation. Mutually exclusive distribution of genetic and epigenetic alterations reflects differently biological characteristics in the etiology of lung adenocarcinomas.     

Systolic cessation of the flow in the mid stent segment of the previously stented ostial vein graft with normal flow during diastole. A case report and brief review.

We present a case of intermittent cessation of blood flow through stent struts during systole, with normal flow during diastole in the previously stented ostial vein graft. After reviewing the initial procedure, we discovered that the operator had difficulty in positioning the stent. After stent deployment, the ostial stent was malpositioned and was protruding more than 50% into the aorta. During systole, the contrast in the stent struts, which are situated in the aorta, was being washed off by systolic blood flow, while in the diastole, the flow of contrast was normal. This is the first case report of this observation with a brief review.     

Induction of Protective Immunity in Rodents by Vaccination with a Prokaryotically Expressed Recombinant Fusion Protein Containing a Respiratory Syncytial Virus G Protein Fragment

A subunit approach to the development of a respiratory syncytial virus (RSV) vaccine was investigated. It involved the production, inEscherichia coli,of an RSV (Long) G protein fragment (G2Na) as a C-terminal fusion partner to an albumin binding region (BB) of streptococcal protein G. G2Na incorporated amino acid residues 130–230 and was specifically recognized by murine anti-RSV-A polyclonal serum. In mice, intraperitoneal immunization with BBG2Na induced high anti-RSV-A serum ELISA titers and low to moderate neutralization activity. The immune response induced by BBG2Na demonstrated a potent protective efficacy against upper and lower respiratory tract RSV-A infection. The immunogenicity and protective efficacy of BBG2Na was maintained for at least 47 and 48 weeks, respectively, and was as potent and durable as live RSV-A administered in a similar fashion. Intramuscular immunization of cotton rats with BBG2Na protected lungs from both homologous and heterologous virus challenge. In contrast to mice, however, cotton rat nasal tracts were not protected after BBG2Na immunization. Consistent with antibody-mediated protection, virus was cleared within 24 hr from the lungs of BBG2Na-immunized mice. The anti-RSV-A antibodies induced in mice were exclusively of the IgG1 isotype and were detected in the serum, lungs, and nasal tracts. Passive transfer of these antibodies prevented acute, and eliminated chronic, RSV-A lung infection in normal and immunodeficient mice, respectively, confirming that such antibodies are important and sufficient for BBG2Na-induced pulmonary protection. Our results clearly demonstrate that BBG2Na contains an important immunogenic domain of the RSV G protein. The prokaryotic origin of this protein indicates that glycosylation of the RSV G protein is not necessary for protective efficacy. Thus, BBG2Na has potential as an RSV subunit vaccine.     

Origin and primary dispersal of the Mycobacterium tuberculosis Beijing genotype: clues from human phylogeography

We suggest that the evolution of the population structure of microbial pathogens is influenced by that of modern humans. Consequently, the timing of hallmark changes in bacterial genomes within the last 100,000 yr may be attempted by comparison with relevant human migrations. Here, we used a lineage within Mycobacterium tuberculosis, a Beijing genotype, as a model and compared its phylogeography with human demography and Y chromosome-based phylogeography. We hypothesize that two key events shaped the early history of the Beijing genotype: (1) its Upper Palaeolithic origin in the Homo sapiens sapiens K-M9 cluster in Central Asia, and (2) primary Neolithic dispersal of the secondary Beijing NTF::IS6110 lineage by Proto-Sino-Tibetan farmers within east Asia (human O-M214/M122 haplogroup). The independent introductions of the Beijing strains from east Asia to northern Eurasia and South Africa were likely historically recent, whereas their differential dissemination within these areas has been influenced by demographic and climatic factors.     

Cytokines, allergy, and asthma

PURPOSE OF REVIEW: This review examines recent articles on the relationship of cytokines to allergy and asthma with particular emphasis on immune mechanisms involved in disease development in early life. RECENT FINDINGS: It was previously proposed that reduced microbial exposure in early life is responsible for a shift of the Th1/Th2 balance in the immune system towards the proallergenic Th2 response. This Th1/Th2 imbalance results in the clinical expression of allergy and/or asthma. In recent years, accumulating data from mice and humans have identified Th2 cytokines [interleukin (IL)-4, IL-13, and IL-5] as major contributors to allergy and asthma. Interestingly, the Th1 cytokine interferon-gamma has recently been shown to act concurrently with Th2 cytokines in maintaining the chronic inflammatory response in allergic diseases, particularly in asthmatic airways. Most recently, evidence suggests that suppression of T-regulatory cells may contribute to the underlying immune mechanisms involved in allergy and asthma. SUMMARY: An enhanced Th2 immune response and the elaboration of cytokines such as IL-4, IL-13, and IL-5 contribute to the induction of allergy and asthma. Interferon-gamma, a Th1 cytokine, acts in conjunction with Th2 (IL-4, IL-13, and IL-5) in maintaining chronic allergic inflammation. The mechanisms leading to an enhanced Th2 response are still controversial. Th2-dominated immune responses may result from immune suppression of T-regulatory cells as well as Th1 cells. Understanding early-life immune mechanisms responsible for atopic diseases, specifically how cytokines of T-regulatory cells act to balance the Th1 and Th2 immune response, continues to be a fruitful area of research.     

Key Informants’ Perspectives on Childhood Obesity in Vietnam: A Qualitative Study

Maternal and Child Health Journal - Vietnam’s post-war globalization, economic development, and urbanization have contributed to a nutrition transition from traditional diets to...     

Long-pulsed 1064-nm and 755-nm lasers for C1 leg veins on skin type IV patients: a side-by-side comparison

Lasers in Medical Science - Long-pulsed 1064-nm (LP1064) and 755-nm (LP755) lasers have been demonstrated as effective treatments for leg veins. However, few studies of these treatments on Asian...     

Urgent desensitization in patients bridged to heart transplantation under extracorporeal membrane oxygenation support: A preliminary experience

Antihuman leukocyte antigen (HLA) antibodies restrict the access to cardiac allografts. Desensitization therapy is a major challenge in patients with cardiogenic shock waiting for urgent heart transplantation (HT). We retrospectively reviewed six patients (mean age of 37.5 years [16–70]) who underwent plasmapheresis (PP) under extracorporeal membrane oxygenation (ECMO) before transplant between January 2017 and September 2018. The average duration of follow‐up was 25 months [20–32]. Mean fluorescence intensity (MFI) of HLA‐specific antibodies was reported as follows: score 4 for MFI < 1000, score 6 for 1000 < MFI < 3000 and score 8 for MFI > 3000. The mean duration of ECMO support was 29 days [1–74] and 6.8 [1–29] PP sessions were performed per patient before transplant. The mean number of HLA‐specific antibodies before HT was 9.6 for score 6 [4–13] and 5.8 for score 8 [1–12]. Four patients had major complications after transplantation (2 hemorrhagic shocks, 5 infectious events). Mean MFI reduction rate was 94% [79–100] for Class I and 44.2% for Class II [0–83]. Hospital survival was 100%, and early antibody‐mediated rejection was diagnosed in one patient at 7 days after HT. Plasmapheresis under ECMO support was associated with favorable early outcomes in highly sensitized candidates for urgent heart transplantation.