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.     

Chronic pulmonary manifestations of varicella in adults. Apropos of 2 cases

The pulmonary manifestations of varicella are observed more frequently in adults than in children. They make present according to 3 modes: acute, subacute or chronic. The authors report 2 cases of chronic pulmonary manifestations in the form of diffuse, partially calcified micronodular lesions of both lung fields observed in the course of varicella in adults.     

Mechanism of strength increase for a hydrothermal porcelain.

OBJECTIVES: The objectives of this study were to verify the formation of a hydrolyzed surface layer on Duceram LFC, to determine the effects of such a layer on mechanical material properties, and to identify a specific mechanism responsible for any strength increase observed. METHODS: Specimens were fabricated from dentin porcelain by a vibration blotting technique and were prepared to have either blunt or sharp surface flaws. Half of the specimens underwent accelerated aging. Specimens were fractured in three-point flexure to measure their strength, and fractographic analysis was used to determine fracture toughness and residual surface stress. Surface hardness and elastic modulus were measured using a microindentation method. Porcelain surface topography was examined using atomic force microscopy, and Fourier transform infrared spectroscopy was used to determine the composition of the surface layer. RESULTS: The aging treatment modified the porcelain surface topography but did not create a layer with increased hydroxyl ion content. Porcelain strength increased upon aging, and the increase was proportional to initial flaw severity. The apparent fracture toughness of sharp flaw specimens increased to match that for specimens containing blunt flaws upon aging. Surface hardness and elastic modulus decreased upon aging. SIGNIFICANCE: Previous studies on the strength increase of hydrothermal porcelain were contradictory because a variety of specimen preparation procedures were used. This study resolves the apparent contradiction by determining the effect of specimen preparation on material strength.     

Pseudotumoral organization of a twisted epiploic fringe or 'hard-boiled egg' in the peritoneal cavity.

A freely moving pseudotumoral formation resembling a peeled "hard-boiled egg" was discovered in the abdominal cavity of an 82-year-old male patient during exploratory laparotomy for assessment of hepatocarcinoma in the left lobe of the liver. The formation involved a twisted epiploic fringe, which was necrotic, sclerotic, and calcified. The absence of any attachment and the avascular aspect of this pseudotumor suggest a possibly self-sustaining mechanism for the laminar sclerosis organized around the necrotic adipose tissue.     

Molecular epidemiology of hepatitis B virus infections in Denmark.

BACKGROUND: Denmark has a low incidence of acute hepatitis B (HBV) infections but the impact of an increasing number of immigrants with chronic HBV infection on HBV transmission is unknown. OBJECTIVES: To characterise individuals with chronic and acute HBV infection in a defined region and to examine the importance of different risk groups for the current HBV transmission. METHODS: During 2000-2001 all consecutive HBV infected individuals routinely diagnosed through the regional HBV serology laboratory in the County of Funen were classified according to ethnicity, presumed route of transmission and stage of infection based on clinical data mainly supplied by the requesting physician. HBV DNA was sequenced and subjected to phylogenetic analysis. RESULTS: Of 309 identified cases, 91 (29%) were classified as acute infection. HBV DNA sequencing was possible in 54 (59%) of these cases. Phylogenetic analysis showed that HBV isolated from injecting drug users (IDUs) was identical or closely related. Among acute cases acquired in Denmark 89% (74/83) were seen in IDUs (65) or in individuals presumably exposed to IDUs (nine) and phylogenetic analysis corroborated the assumption of IDU related transmission in every case with available sequence data. Among 83 ethnic Danes who acquired their HBV infection in Denmark, no new cases of transmission from immigrants were detected. CONCLUSION: Injecting drug use was the single most important factor for hepatitis B transmission in Denmark. The current Danish vaccination strategy is unable to protect IDUs from HBV infection and IDUs pose a greater risk of HBV transmission to the general population than immigrants.     

IL-5 is essential for vaccine-induced protection and for resolution of primary infection in murine filariasis

The pathways conferring immunity to human filariases are not well known, in part because human-pathogenic filariae do not complete a full life cycle in laboratory mice. We have used the only fully permissive infection of mice with filariae, i.e., infection of BALB/c mice with the rodent filarial nematode Litomosoides sigmodontis. Our previous results showed that worm development is inversely correlated with Th2 cytokine production and eosinophilia. The scope of the present study was to directly elucidate the role of interleukin-5 (IL-5) and eosinophils in controlling the development of L. sigmodontis after vaccination and in primary infection. BALB/c mice immunized with irradiated third-stage larvae (L3) were confirmed to have elevated IL-5 levels as well as high subcutaneous eosinophilia and to attack and reduce incoming larvae within the first 2 days, resulting in 70% reduction of worm load. Treatment of vaccinated mice with anti-IL-5 antibody (TRFK-5) suppressed both blood and tissue eosinophilia and completely abolished protection. This demonstrates, for the first time in a fully permissive filarial infection, that IL-5 is essential for protection induced by irradiated L3 larvae. In contrast, in primary-infected mice, anti-IL-5 treatment did not modify filarial infection within the 1st month, most likely because during primary infection IL-5-dependent mechanisms such as subcutaneous eosinophilia are induced too late to disturb worm establishment. However, there is a role for IL-5 late in primary infection where neutrophil-dependent worm encapsulation is also under the control of IL-5. Received: 30 March 2000     

Comparison of local risk factors for children's atopic symptoms in Hanoi, Vietnam

BACKGROUND: A 1999 study in Hanoi, Vietnam using the International Study on Asthma and Allergies in Childhood (ISAAC) questionnaire showed a high prevalence of atopic symptoms. Identifying risk factors for symptoms in these children may help in understanding the causes for these high estimates. METHODS: An ISAAC questionnaire with supplemental questions on environmental variables was distributed to 5495 school children in Hanoi and a suburban district, Dong Anh. The response rate was 65.7%. RESULTS: In Dong Anh, the following were among the significant age and gender adjusted associations: pig ownership [odds ratio (OR) (95% confidence interval), OR = 1.79 (1.18-2.70) for doctor-diagnosed asthma (DDA), OR = 1.72 (1.08-2.78) for doctor diagnosed hay fever (DDHF)] and farming [OR = 1.67 (1.27-2.19) for ever asthma, OR = 1.51 (1.09-2.09) for DDHF]. In multivariate models, tuberculosis (TB) was a significant predictor of atopic symptoms [Hanoi: OR = 3.09 (1.10-8.70) for DDA, Dong Anh: OR = 3.71 (1.40-9.84) for DDA, OR = 4.66 (1.88-11.57) for DDHF]. CONCLUSIONS: These findings are contrary to the "hygiene hypothesis". Recent immunologic and epidemiologic studies refute the inverse association between allergy and TB and may be one explanation for the positive association in this study. The positive association with pig ownership and farming may be because of exposures on farms in a developing country that may be different from exposures in farms of developed countries.     

Severe Acute Respiratory Syndrome Coronavirus 2 Seropositivity among Healthcare Personnel in Hospitals and Nursing Homes,Rhode Island,USA, July–August 2020

Healthcare personnel are recognized to be at higher risk for infection with severe acute respiratory syndrome coronavirus 2. We conducted a serologic survey in 15 hospitals and 56 nursing homes across Rhode Island, USA, during July 17–August 28, 2020. Overall seropositivity among 9,863 healthcare personnel was 4.6% (95% CI 4.2%–5.0%) but varied 4-fold between hospital personnel (3.1%, 95% CI 2.7%–3.5%) and nursing home personnel (13.1%, 95% CI 11.5%–14.9%). Within nursing homes, prevalence was highest among personnel working in coronavirus disease units (24.1%; 95% CI 20.6%–27.8%). Adjusted analysis showed that in hospitals, nurses and receptionists/medical assistants had a higher likelihood of seropositivity than physicians. In nursing homes, nursing assistants and social workers/case managers had higher likelihoods of seropositivity than occupational/physical/speech therapists. Nursing home personnel in all occupations had elevated seropositivity compared with hospital counterparts. Additional mitigation strategies are needed to protect nursing home personnel from infection, regardless of occupation.     

Elevated serum cytokines in patients with malignancy and weight-loss

Tumour necrosis factor (TNF) has been implicated in the pathogenesis of cachexia in neoplastic and infectious diseases. In our study, the relationship between TNF and other cytokines in patients with malignancy was studied by measuring the serum levels of TNF, Interleukin-I (IL-1), Interleukin-2 (IL-2), and Interleukin-6 (IL-6). Eight patients with cancer had weight loss >10% of their body weight prior to starting anticancer therapy, and their weight loss was not attributable to gastrointestinal disorder, or other medical conditions. Seven patients with malignancy and no weight loss, as well as three normal donors without malignancy were also tested as controls. TNF, IL-1, IL-2 and IL-6 serum levels were determined using a quantitative ELISA test. Elevated levels of TNF, IL-1, IL-2 and IL-6 were detected in 25%, 12.5%, 12.5% and 50% of patients, respectively. In contrast, TNF levels were elevated in 28.5% of seven patients with cancer and no weight loss. In these patients, IL-1, IL-2 and IL-6 levels were undetectable. No TNF, IL-1, IL-2 or IL-6 could be detected in the sera of normal controls. Elevated cytokines serum levels, and especially IL-6, are detected in patients with cancer-cachexia. The determination of such cytokines may have a prognostic value.     

Conversion factor for comparison of data from Humphrey and Medmont automated perimeters

Background : Clinical experience has shown that the sensitivity indices reported by the Humphrey Field Analyser (HFA) are generally higher than those given by the Medmont Automated Perimeter (M600). It is the purpose of this paper to determine a conversion factor for the two perimeters and to confirm this prediction using clinical data. Theory predicted that HFA_sensitivity ? 5 dB = M600_sensitivity. Methods : Sensitivity versus eccentricity profiles were measured over the central visual field on 10 young subjects using both perimeters. Results : Both the HFA and the M600 operate within the realms of the Weber law and measure similar Weber fractions. The sensitivity profiles had similar slopes (about ?0.2 dB/degree) and were separated by about six decibels with the HFA reporting higher sensitivity values. This result confirmed the theoretical prediction. Conclusion : The difference in threshold sensitivities between the two perimeters is a result of differences in scaling factors and instrument luminances. A suggested clinical conversion factor is to subtract 5 dB from the HFA data to approximate those of the M600.