HLA polymorphisms are associated with Helicobacter pylori infected gastric cancer in a high risk population, China

Helicobacter pylori is one of the most common bacterial infections associated with an increased risk of gastric cancer, but its association with host factors, particularly polymorphisms of the immune response genes, such as human leukocyte antigen (HLA) genes, is still unclear. To investigate the role of HLA polymorphisms in the risk of gastric cancer among subjects with H. pylori infection, a case-control study involving 52 gastric cancer patients and 139 non-cancer controls was conducted in Linqu County, China, an area with a high incidence of gastric cancer. Polymorphisms of HLA class I and class II alleles were determined by PCR with sequence-specific primers (PCR-SSP). The information about H. pylori infection was obtained from previous records. Among 48 class I and 19 class II HLA alleles detected in this study, two alleles, CW*03 and DRB1*01, were found to be distributed significantly differently between patients and controls [odds ratio(OR)=1.95, 95% confidence interval (CI)=1.13–3.35, P=0.017 and OR=4.39, 95% CI=1.39–13.84, P=0.012, respectively). The OR of gastric cancer risk in individuals carrying CW*03/CW*03 or CW*03/CW*N was 2.06, 95% CI=1.05–4.02, P=0.035, while the OR was 3.49, 95% CI=1.0–12.4, P=0.04 for DRB1*01/DRB1*01 or DRB1*01/DRB1*N carriers. The analysis of the interaction between H. pylori infection and HLA risk genotypes of CW*03 or DRB1*01 revealed that the effect of CW*03 and DRB1*01 genotypes on gastric cancer risk was manifested stronger in H. pylori-positive individuals (OR=5.30, 95% CI=1.73–16.29, P=0.004 and OR=13.38, 95% CI=2.52–70.98, P=0.002, respectively) than in H. pylori-negative ones (OR=1.25, 95% CI=0.25–6.12, P=0.785 and OR=2.26, 95% CI=0.18–28.88, P=0.531, respectively). The combined effect of the two risk HLA genotypes on gastric cancer risk was also analysed. The result showed that the individuals carrying both the CW*03 and DRB1*01 alleles could only be found in cancer patients (5/52), and not in controls (0/139), further suggesting that CW*03 and DRB1*01 are risk alleles advancing the progression of tumorigenesis. These observations demonstrate that host HLA genotypes may play an important role in the risk of gastric cancer, especially among persons with H. pylori infection.     

Bacterial communities in predatory mites are associated with species and diet types

The symbiotic bacterial communities of phytophagous arthropods are affected by host species and feeding habits, but such effects have been poorly studied in natural enemies. Here, we investigated the entire bacterial microbiome of two species of predatory mites, Neoseiulus californicus and Neoseiulus barkeri, feeding on three types of diets (artificial diet, pollen and their natural prey, the spider mite Tetranychus urticae) by high-throughput sequencing of the 16S rRNA gene. We found that the bacterial diversity of predatory mites feeding on artificial diet was significantly different from pollen and spider mite feeding groups in both N. californicus and N. barkeri, while bacterial diversity also differed strikingly between the two species even when feeding on the same artificial diet. This finding suggests that the bacterial community of predatory mites is determined by both species and diet. Alphaproteobacteria and Gammaproteobacteria were the two dominant bacterial classes in both predatory mite species, except for N. californicus feeding on artificial diet. The bacterium Bosea sp. was detected in all samples as the core microbial species in predatory mites. Additionally, we discuss whether Bradyrhizobiaceae and Rhodobacteraceae bacteria could be used as probiotics in the artificial diet of N. californicus for better mass rearing.

     

Problems associated with identification of Legionella species from the environment and isolation of six possible new species

Following investigation of an outbreak of legionellosis in South Australia, numerous Legionella-like organisms were isolated from water samples. Because of the limited number of commercially available direct fluorescent-antibody reagents and the cross-reactions found with some reagents, non-pneumophila legionellae proved to be difficult to identify and these isolates were stored at -70 degrees C for later study. Latex agglutination reagents for Legionella pneumophila and Legionella anisa developed by the Institute of Medical and Veterinary Science, Adelaide, Australia, were found to be useful as rapid screening aids. Autofluorescence was useful for placing isolates into broad groups. Cellular fatty acid analysis, ubiquinone analysis, and DNA hybridization techniques were necessary to provide definitive identification. The species which were isolated most frequently were L. pneumophila, followed by L. anisa, Legionella jamestowniensis, Legionella quinlivanii, Legionella rubrilucens, Legionella spiritensis, and a single isolate each of Legionella erythra, Legionella jordanis, Legionella birminghamensis, and Legionella cincinnatiensis. In addition, 10 isolates were found by DNA hybridization studies to be unrelated to any of the 26 currently known species, representing what we believe to be 6 possible new species.     

Eicosanoid synthesis and Helicobacter pylori associated gastritis: increase in leukotriene C4 generation associated with H. pylori colonization.

The importance of pro-inflammatory leukotriene C4 in Helicobacter pylori (H. pylori) associated gastritis in man is unknown. Fresh gastric biopsy specimens from 28 dyspeptic patients were obtained: 10 showed normal antral histology with no evidence of H. pylori, the remaining 18 patients exhibited histological gastritis and were H. pylori positive as assessed by histology, culture and urease test. Twelve of these 18 patients received 240 mg twice daily colloidal bismuth subcitrate for four weeks before re-endoscopy. Gastric biopsies from H. pylori positive patients were incubated under basal and Ca(2+)-ionophore mediated conditions: Radioimmunoassay analysis of the supernatant showed basal release of prostaglandin E2 and leukotriene C4 was slightly but not significantly elevated in H. pylori positive mucosa. However in H. pylori positive mucosa there was an 85% increase in leukotriene C4 synthesis when biopsies were incubated with ionophore, compared to only 13% increase in H. pylori negative mucosa (p less than 0.02). After eradication of H. pylori by colloidal bismuth subcitrate, there was a clearance of inflammatory cell infiltrate as assessed by histology and a significant reduction in ionophore-mediated leukotriene C4 formation compared with before treatment (p less than 0.02). These results suggest that H. pylori gastritis is associated with increased capacity to generate leukotriene C4, which may amplify the damaging effects of the bacteria on gastric mucosa.     

1H NMR metabolic profiling of human serum associated with benign and malignant gallstone diseases

Proton NMR based metabolic profile of serum associated with different gallbladder pathologies is presented. Quantitative and qualitative variations in the metabolic profile of serum in control samples and three different pathologies of gallbladder, chronic cholecystitis, xanthogranulomatous cholecystitis and carcinoma of gallbladder has been evaluated by use of ¹H NMR based metabonomics and multivariate chemometric methods. Multivariate partial least square discriminant analysis of ¹H NMR spectra showed a clear discrimination between control and diseased groups on the basis of quantitative and qualitative metabolic variations. Increased levels of lactate and pyruvate whereas decreased levels of glucose, some amino acids and low density lipoprotein/very low density lipoprotein (LDL/VLDL) were observed. These metabolites, responsible for class discrimination, from different metabolic pathways could be considered as the signatures of the carcinoma of gallbladder.     

Problems associated with identification of Legionella species from the environment and isolation of six possible new species.

Following investigation of an outbreak of legionellosis in South Australia, numerous Legionella-like organisms were isolated from water samples. Because of the limited number of commercially available direct fluorescent-antibody reagents and the cross-reactions found with some reagents, non-pneumophila legionellae proved to be difficult to identify and these isolates were stored at -70 degrees C for later study. Latex agglutination reagents for Legionella pneumophila and Legionella anisa developed by the Institute of Medical and Veterinary Science, Adelaide, Australia, were found to be useful as rapid screening aids. Autofluorescence was useful for placing isolates into broad groups. Cellular fatty acid analysis, ubiquinone analysis, and DNA hybridization techniques were necessary to provide definitive identification. The species which were isolated most frequently were L. pneumophila, followed by L. anisa, Legionella jamestowniensis, Legionella quinlivanii, Legionella rubrilucens, Legionella spiritensis, and a single isolate each of Legionella erythra, Legionella jordanis, Legionella birminghamensis, and Legionella cincinnatiensis. In addition, 10 isolates were found by DNA hybridization studies to be unrelated to any of the 26 currently known species, representing what we believe to be 6 possible new species.     

Assessing population increase as a possible outcome to management of invasive species

Some efforts to reduce invasive populations have paradoxically led to population increases. This phenomenon, referred to as overcompensation, occurs when reduced intraspecific pressures increase juvenile survival or maturation rates, leading to increased population size. Overcompensation in response to eradication efforts could derail management efforts, so it would be beneficial to evaluate the likelihood of overcompensation prior to removal. We conducted a series of experiments to examine the potential for overcompensation of a non-native population of the European green crab, Carcinus maenas, which was being removed in Bodega Harbor, California. First, we examined the impact of adults on juvenile survival by measuring adult cannibalism on juveniles in the presence and absence of alternative prey, and the survival of tethered juveniles at varying adult densities. Second, we examined how adult presence affected juvenile short-term foraging and growth rates. Although adult presence reduced juvenile short-term foraging, we detected only minimal cannibalism and found no evidence that adults greatly reduce juvenile growth or survivorship. These results suggest that overcompensation is not likely to occur in this population in response to removal. We assessed this prediction using pre- and post-removal surveys of juvenile recruitment in Bodega Harbor compared to nearby populations, testing for evidence of overcompensation. Relative juvenile abundance did not statistically increase in removal compared to reference populations, consistent with our conclusion from the experiments. This experimental approach which focuses on an organism’s population biology provides a tool to assess capacity for assessing the capacity for overcompensation in management strategies for invasive species.     

AKT1 polymorphisms are associated with risk for metabolic syndrome

Converging lines of evidence suggest that AKT1 is a major mediator of the responses to insulin,insulin-like growth factor 1 (IGF1), and glucose. AKT1 also plays a key role in the regulation of both muscle cell hypertrophy and atrophy. We hypothesized that AKT1 variants may play a role in the endophenotypes that makeup metabolic syndrome. We studied a 12-kb region including the ?rst exon of the AKT1 gene for association with metabolic syndrome-related phenotypes in four study populations [FAMUSS cohort (n = 574; age 23.7 ± 5.7 years), Strong Heart Study (SHS) (n = 2,134; age 55.5 ± 7.9 years), Dynamics of Health, Aging and Body Composition (Health ABC) (n = 3,075; age 73.6 ± 2.9 years), and Studies of a Targeted Risk Reduction Intervention through De?ned Exercise (STRRIDE)(n = 175; age 40–65 years)]. We identi?ed a three SNP haplotype that we call H1, which represents the ancestral alleles eles at the three loci and H2, which represents the derived alleles at the three loci. In young adult European Americans (FAMUSS), H1 was associated with higher fasting glucose levels in females. In middle age Native Americans (SHS), H1 carriers showed higher fasting insulin and HOMA in males, and higher BMI in females. Inolder African-American and European American subjects(Health ABC) H1 carriers showed a higher incidence of metabolic syndrome. Homozygotes for the H1 haplotype showed about twice the risk of metabolic syndrome in both males and females (p\0.001). In middle-aged European Americans with insulin resistance (STRRIDE) studied by intravenous glucose tolerance test (IVGTT), H1 carriers showed increased insulin resistance due to the Sg component (p = 0.021). The 12-kb haplotype is a risk factor for metabolic syndrome and insulin resistance that needs to be explored in further populations.     

Skin diseases associated with Malassezia species in humans. Clinical features and diagnostic criteria

Malassezia yeasts not only cause the well known pityriasis versicolor and folliculitis, but also play an important role in other skin diseases, including seborrheic dermatitis and atopic dermatitis. The presence of Malassezia yeasts may be confirmed by direct microscopic examination and cultures of skin scrapings. In pityriasis versicolor the direct microscopic examination is the rapidest and surest test for confirming the clinical diagnosis. The preparation will show a cluster of globose budding spores with thick or double wall and short hyphae. For detecting Malassezia in the other diseases the cultures is preferable. Culture is useful both for confirming the clinical diagnosis and for epidemiological investigations. The identification of the Malassezia species is not easy. The microscopic observation of the colony direct towards the identification of Malassezia species, but it is not enough to identify the colonies definitely. Several biochemical tests are necessary for a precise identification, such as catalase reaction, growth on media without lipid sources, ability to utilize hydrophilic emulsifiers as sole lipid source, esculin test, tryptophan test.     

CTLA4 polymorphisms are associated with vitiligo, in patients with concomitant autoimmune diseases

The cytotoxic T lymphocyte antigen4 (CTLA4) gene plays a critical role in the control of T cell activation. The gene encodes a surface molecule with inhibitory effects on activated T cells. Several studies have disclosed an association between the previously known variants of the CTLA4 gene and autoimmune disorders, but no study has as yet found any definite association between vitiligo and the CTLA4 polymorphisms. A recent study identified new candidate susceptibility polymorphisms in this region, associated with differential gene splicing and thereby the relative abundance of soluble CTLA4. To assess these new polymorphisms in patients with vitiligo, we genotyped 100 vitiligo patients and 140 healthy controls from the UK, for these novel polymorphisms. No association was found in patients with isolated vitiligo, but a significant association was seen in patients with vitiligo and other autoimmune diseases. The results indicate that the polymorphisms in the CTLA4 gene region confer susceptibility to vitiligo when occurring together with other autoimmune diseases, but not in patients with isolated vitiligo. This raises the possibility that there are two distinct forms of vitiligo where only a subgroup of patients may have a disease caused by the autoimmune destruction of melanocytes.     

The possible role of contact current in cancer risk associated with residential magnetic fields

Residential electrical wiring safety practices in the US result in the possibility of a small voltage (up to a few tenths of a volt) on appliance surfaces with respect to water pipes or other grounded surfaces. This "open circuit voltage" (V(OC)) will cause "contact current" to flow in a person who touches the appliance and completes an electrical circuit to ground. This paper presents data suggesting that contact current due to V(OC) is an exposure that may explain the reported associations of residential magnetic fields with childhood leukemia. Our analysis is based on a computer model of a 40 house (single-unit, detached dwelling) neighborhood with electrical service that is representative of US grounding practices. The analysis was motivated by recent research suggesting that the physical location of power lines in the backyard, in contrast to the street, may be relevant to a relationship of power lines with childhood leukemia. In the model, the highest magnetic field levels and V(OC)s were both associated with backyard lines, and the highest V(OC)s were also associated with long ground paths in the residence. Across the entire neighborhood, magnetic field exposure was highly correlated with V(OC) (r = 0.93). Dosimetric modeling indicates that, compared to a very high residential level of a uniform horizontal magnetic field (10 mu T) or a vertical electric field (100 V/m), a modest level of contact current (approximately 18 mu A) leads to considerably greater induced electric fields (> 1 mV/m) averaged across tissue, such as bone marrow and heart. The correlation of V(OC) with magnetic fields in the model, combined with the dose estimates, lead us to conclude that V(OC) is a potentially important exposure with respect to childhood leukemia risks associated with residential magnetic fields. These findings, nonetheless, may not apply to residential service used in several European countries or to the Scandinavian studies concerned with populations exposed to magnetic fields from overhead transmission lines.