Aspergillus section Flavi and aflatoxins in Algerian wheat and derived products

Wheat and its derivatives are a very important staple food for North African populations. The aim of this study was to analyze populations of Aspergillus section Flavi from local wheat based on aflatoxins (AFs), cyclopiazonic acid (CPA) and sclerotia production, and also to evaluate AFs-contaminated wheat collected from two different climatic regions in Algeria. A total of 108 samples of wheat were collected during the following phases: pre-harvest, storage in silos and after processing. The results revealed that among the Aspergillus species isolated, those belonging to section Flavi were predominant. Of the 150 strains of Aspergillus section Flavi isolated, 144 were identified as Aspergillus flavus and 6 as Aspergillus tamarii. We showed that 72% and 10% of the A. flavus strains produced AFs and CPA, respectively. Among the 150 strains tested, 60 produced amounts of AFB1 ranging from 12.1 to 234.6 μg/g of CYA medium. Also, we showed that most strains produced large sclerotia. AFB1was detected by HPLC in 56.6% of the wheat samples and derived products (flour, semolina and bran) with contamination levels ranging from 0.13 to 37.42 μg/kg.     

Genome-wide association study of the TP53 R249S mutation in hepatocellular carcinoma with aflatoxin B1 exposure and infection with hepatitis B virus

BackgroundExposure to dietary aflatoxin B1 (AFB1) induces DNA damage and mutation in the TP53 gene at codon 249, known as the TP53 R249S mutation, and is a major risk factor for hepatocellular carcinoma (HCC). AFB1 and the hepatitis B virus (HBV) together exert synergistic effects that promote carcinogenesis and TP53 R249S mutation in HCC.MethodsA genome-wide association study (GWAS) of whole genome exons was conducted using 485 HCC patients with chronic HBV infection. This was followed by an independent replication study conducted using 270 patients with chronic HBV infection. Immunohistochemistry was used to evaluate TP53 expression in all samples. This showed a correlation between codon 249 mutations and TP53 expression. Susceptibility variants for the TP53 R249S mutation in HCC were identified based on both the GWAS and replication study. The associations between identified variants and the expression levels of their located genes were analyzed in 20 paired independent samples.ResultsThe likelihood of positive TP53 expression was found to be higher in HCC patients with the R249S mutation both in the GWAS (P<0.001) and the replication study (P=0.006). The combined analyses showed that the TP53 R249S mutation was significantly associated with three single nucleotide polymorphisms (SNPs): ADAMTS18 rs9930984 (adjusted P=4.84×10⁻⁶), WDR49 rs75218075 (adjusted P=7.36×10⁻⁵), and SLC8A3 rs8022091 (adjusted P=0.042). The TP53 R249S mutation was found to be highly associated with the TT genotypes of rs9930984 (additive model, P=0.01; dominant model, P=6.43×10⁻⁵) and rs75218075 (additive model, P=0.002; dominant model, P=2.16×10⁻⁴). Additionally, ADAMTS18 mRNA expression was significantly higher in HCC tissue compared with its expression in paired non-tumor tissue (P=0.041), and patients carrying the TT genotype at rs9930984 showed lower ADAMTS18 expression in non-tumor tissue compared with patients carrying the GT genotype (P=0.0028). WDR49 expression was markedly lower in HCC tissue compared with paired non-tumor tissue (P=0.0011).ConclusionsTP53 expression is significantly associated with the R249S mutation in HCC. Our collective results suggest that rs9930984, rs75218075, and rs8022091 are associated with R249S mutation susceptibility in HCC patients exposed to AFB1 and HBV infection.     

Aflatoxin B1 DNA-Adducts in Hepatocellular Carcinoma from a Low Exposure Area

Aflatoxin B1 (AFB1) is a class 1 carcinogen with an ascertained role in the development of hepatocellular carcinoma (HCC) in high exposure areas. Instead, this study aimed to assay whether chronic/intermittent, low-dose AFB1 consumption might occur in low-exposure geographical areas, ultimately accumulating in the liver and possibly contributing to liver cancer. AFB1-DNA adducts were assayed by immunostaining in liver tissues from three Italian series of twenty cirrhosis without HCC, 131 HCC, and 45 cholangiocarcinoma, and in an AFB1-induced HCC rat model. CD68, TP53 immunostaining, and TP53 RFLP analysis of R249S transversion were used to characterize cell populations displaying AFB1-DNA adducts. Twenty-five HCCs displayed AFB1-adducts both in neoplastic hepatocytes and in cells infiltrating the tumor and non-tumor tissues. Nuclear immunostaining was observed in a few cases, while most cases showed cytoplasmic immunostaining, especially in CD68-positive tumor-infiltrating cells, suggestive for phagocytosis of dead hepatocytes. Similar patterns were observed in AFB1-induced rat HCC, though with higher intensity. Cholangiocarcinoma and cirrhosis without HCC did not displayAFB1-adducts, except for one case. Despite not providing a causal relationship with HCC, these findings still suggest paying attention to detection and control measures for aflatoxins to ensure food safety in low exposure areas.     

The trend of pulmonary tuberculosis in patients seen at DOTS clinics in the Federal Capital Territory, Abuja, Nigeria

We evaluated the pattern of sputum smear positivity and assessed the effects of directly observed treatment short course (DOTS) among tuberculosis (TB) patients at the DOTS clinics in the Federal Capital Territory (FCT), Abuja. In total, 1391 patients were seen at six microscopy and treatment centres across the FCT between January and December 2003. Their sputa were screened microscopically for the presence of acid-fast bacilli (AFB) using the Ziehl-Neelsen staining technique. In total, 296 (21.3%) patients were smear positive; 201 (67.9%) were new cases and 95 (32.1%) were follow-up cases. The highest incidence of sputum smear positivity (24.8%) was found in those aged 21-30 years and the lowest incidence (6%) was found in those aged 71 years and above. No incidence of smear positivity was recorded in children aged 0-10 years. In total, 160 of the men screened were AFB positive (75% new cases, 25% follow-up cases). In comparison, 136 women were AFB positive (59.6% new cases, 40.4% follow-up cases). During the 1-year study period, two deaths were recorded. Men pose a serious threat to public health as most of the follow-up cases result in the tubercle bacilli developing resistance to available anti-TB drugs. This study demonstrated a high prevalence of infectious TB in the population screened, and therefore underlines the need for capacity building through a multisectoral approach in the fight against the disease. Cohort analysis should be the cardinal management strategy in evaluating the effectiveness of TB control through systemic follow-up and reporting of certain indicators in treatment progress and success.     

Influence of Staging in Superior Sulcus (Pancoast) Tumors of the Lung

Fifty-three patients with superior sulcus (Pancoast) tumors of the lung followed for up to 12 years by the Armed Forces Central Medical Registry were divided into three groups. In Group 1, preoperative staging as determined by bone, brain, and liver scans or combinations thereof and the presence of local nodal extension as determined by mediastinoscopy or scalene fat pad biopsy were negative. These 16 patients received preoperative irradiation followed by en bloc resection of the lung and of the involved chest wall in most of them. Five-year survival as determined by the actuarial method was 49.7%. The 12 patients in Group 2 either had localized nodal involvement or were not diagnosed preoperatively. Survival in this group was 13.1%. Group 3 patients were considered inoperable and were given palliative irradiation. There were 25 patients in this group, and survival was 5.5% at 4 years. It would appear that preoperative irradiation and en bloc resection give improved survival in those patients judged free from metastatic disease preoperatively.     

Vibrio hand infections: a case report and review of the literature

A case of Vibrio vulnificus infection of the hand is presented. The role of Vibrio species as primary pathogens in infections associated with exposure to a marine environment is discussed.     

Effects of ultraviolet radiation on the pathogenesis of Mycobacterium lepraemurium infection in mice

The purpose of this study was to determine whether exposing mice to ultraviolet radiation (UVR) would alter the pathogenesis of infection with Mycobacterium lepraemurium (MLM), which causes a chronic, progressive, lethal disease in susceptible mouse strains. BALB/c mice were irradiated on dorsal skin with various doses of UVR from FS40 sunlamps 3 days before infection with MLM in the hind footpad. The course of disease was followed by assessing the number of acid-fast bacteria in the footpad, regional lymph node and spleen, and measuring the size of the lesion at the site of MLM infection at various times after infection. Mice were also tested periodically for a delayed-type hypersensitivity (DTH) response by injecting MLM antigen into the uninfected footpad and measuring footpad swelling 24 hours later. Mice treated with a single high dose of UVR (45 kJ/m2) had significantly more bacteria in the infected footpad, lymph node and spleen than unirradiated control animals. They also had larger lesions at the site of MLM infection and exhibited significant suppression of the DTH response at 3 and 6 months after infection. Injection of mice s.c. in the footpad with MLM 3d after 45 kJ/m2 UVR reduced the median survival time from 391 to 305 d and after i.v. infection from 171 to 139 d. Dose-response studies indicated that exposing mice to 2.3 kJ/m2 of UVR, which is approximately 1 minimal erythemal dose for this strain, suppressed the DTH response by 50% at 3 months after infection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Estrogen use — Risk of endometrial carcinoma

A retrospective analysis was carried out to determine the prior usage rate of exogenous estrogens in all patients treated for adenocarcinoma of the endometrium in our institution from 1960 to 1974, and in a series of matched controls. Hospital records were reviewed, and patients were matched with controls who had a different gynecologic malignancy. The crude usage rate for all patients with endometrial carcinoma was 18.4% compared with 9.2% of controls yielding a relative risk of 2.2. There was a statistically significant increase in estrogen exposure since 1970, but the risk did not change. Hypertension, diabetes mellitus, and obesity were significant risk factors by themselves, but estrogen exposure in these patients did not appear to put them at further increased risk. There was no significant difference between the exposed and nonexposed groups in respect to grade or stage. In spite of a low exposure rate in this area, the relative risk for estrogen exposure was significant, independent of other variables.