Helicobacter pylori Infection and Gastric Autoimmune Diseases: Is There a Link?

Background. Helicobacter pylori is thought to be involved in atrophic body gastritis. We explored the prevalence of H. pylori infection in asymptomatic subjects with gastric parietal cell antibodies, as well as in patients with pernicious anemia, to evaluate a possible role of H. pylori gastric infection in gastric autoimmunity. Patients and Methods. We studied 79 consecutive asymptomatic subjects with parietal cell antibodies, 24 patients with pernicious anemia, and 66 parietal cell antibody‐negative controls. All patients underwent gastric biopsies for histology and detection of H. pylori. Red blood cell count and volume, serum levels of gastrin, pepsinogen I, iron, folic acid, vitamin B₁₂, and circulating antibodies to H. pylori and to intrinsic factor were also determined. Results. We found an atrophic body gastritis in 14 of the 79 asymptomatic subjects with parietal cell antibodies (18%) and in 2 of the 66 controls (3%) (p = .01). Mean levels of gastrin were increased (p < .0001), while those of pepsinogen were reduced (p < .001) compared with controls. H. pylori was identified at the gastric level and/or circulating anti‐H. pylori antibodies were detected in 46 parietal cell antibody‐positive subjects (58%) compared with 26 controls (39%) (p = .03). In patients with pernicious anemia we found an atrophic body gastritis in 18 of 24 cases (75%) (p < .001 vs. controls). Mean levels of gastrin were markedly increased (p < .0001) and those of pepsinogen I decreased (p < .0001) relative to controls. Only five of these patients (21%) had evidence of H. pylori infection compared with 46 of the parietal cell antibody‐positive subjects (58%) (p = .003) and 26 of the controls (39%). Considering all patients with gastric autoimmunity (i.e. with parietal cell antibodies and/or with pernicious anemia), H. pylori was found in 44 of 72 of those without atrophy (61%) but in 6 of 31 with gastric body atrophy (19%) (p < .001), indicating that H. pylori infection is greatly reduced when gastric acid secretion decreases. Conclusions. The frequent detection of H. pylori infection in subjects with early gastric autoimmunity, indicated by the presence of parietal cell antibodies, suggests that H. pylori could have a crucial role in the induction and/or the maintenance of autoimmunity at the gastric level.     

DCC: Is there a connection between tumorigenesis and cell guidance molecules?

Based on the findings reviewed above, DCC remains a strong candidate for the tumor suppressor gene in the 18q21 region that is presumed to be frequently inactivated in colorectal and a number of other cancer types. Although little is known of the specific mechanisms that account for the loss of its expression in most cancers, the recent studies demonstrating an association between loss of DCC expression in colorectal cancers and poor prognosis imply that DCC inactivation may have very significant effects on the cancer cell phenotype. DCC function in normal and cancer cells is still relatively poorly understood. However, recent studies have begun to provide some insights. Based on the results of a number of recent studies, DCC appears likely to have a role in significant role in differentiation, cell fate determination, and migration in the nervous system and perhaps other tissues as well. Though many additional studies are needed to characterize DCC function more definitively, it seems reasonable to predict that such studies are likely to provide new insights into growth control pathways in normal and cancer tissues.     

Obesity and the rate of time preference: is there a connection?

It is hypothesized that recent trends in US and worldwide obesity are, in part, related to an increase in the marginal rate of time preference, where time preference refers to the rate at which people are willing to trade current benefit for future benefit. The higher the rate of time preference, the larger is the factor by which individuals discount the future health risks associated with current consumption. Data from the United States, as well as international evidence, suggest that a relationship between these two variables is plausible. The authors encourage researchers to explore the possible link between obesity and time preference, as important insights are likely to result.     

Fungal virulence, vertebrate endothermy, and dinosaur extinction: is there a connection?

Fungi are relatively rare causes of life-threatening systemic disease in immunologically intact mammals despite being frequent pathogens in insects, amphibians, and plants. Given that virulence is a complex trait, the capacity of certain soil fungi to infect, persist, and cause disease in animals despite no apparent requirement for animal hosts in replication or survival presents a paradox. In recent years studies with amoeba, slime molds, and worms have led to the proposal that interactions between fungi and other environmental microbes, including predators, select for characteristics that are also suitable for survival in animal hosts. Given that most fungal species grow best at ambient temperatures, the high body temperature of endothermic animals must provide a thermal barrier for protection against infection with a large number of fungi. Fungal disease is relatively common in birds but most are caused by only a few thermotolerant species. The relative resistance of endothermic vertebrates to fungal diseases is likely a result of higher body temperatures combined with immune defenses. Protection against fungal diseases could have been a powerful selective mechanism for endothermy in certain vertebrates. Deforestation and proliferation of fungal spores at cretaceous-tertiary boundary suggests that fungal diseases could have contributed to the demise of dinosaurs and the flourishing of mammalian species.     

DNA damage in telomeres and mitochondria during cellular senescence: is there a connection?

Cellular senescence is the ultimate and irreversible loss of replicative capacity occurring in primary somatic cell culture. It is triggered as a stereotypic response to unrepaired nuclear DNA damage or to uncapped telomeres. In addition to a direct role of nuclear DNA double-strand breaks as inducer of a DNA damage response, two more subtle types of DNA damage induced by physiological levels of reactive oxygen species (ROS) can have a significant impact on cellular senescence: Firstly, it has been established that telomere shortening, which is the major contributor to telomere uncapping, is stress dependent and largely caused by a telomere-specific DNA single-strand break repair inefficiency. Secondly, mitochondrial DNA (mtDNA) damage is closely interrelated with mitochondrial ROS production, and this might also play a causal role for cellular senescence. Improvement of mitochondrial function results in less telomeric damage and slower telomere shortening, while telomere-dependent growth arrest is associated with increased mitochondrial dysfunction. Moreover, telomerase, the enzyme complex that is known to re-elongate shortened telomeres, also appears to have functions independent of telomeres that protect against oxidative stress. Together, these data suggest a self-amplifying cycle between mitochondrial and telomeric DNA damage during cellular senescence.     

Alternative lengthening of telomeres (ALT) and chromatin: is there a connection?

The acquisition of cellular immortality is a critical step in the tumorigenic process that requires stabilization of the telomeres, nucleoprotein structures at the termini of chromosomes. While the majority of human tumors stabilize their telomeres through activation of telomerase (hTERT), a significant portion (10-15%) utilize a poorly understood alternative mechanism of telomere maintenance referred to as ALT (Alternative Lengthening of Telomeres). Strikingly, the ALT mechanism is more prevalent in tumors arising from tissues of mesenchymal origin than in those of epithelial origin. This observation suggests that cell type specific mechanisms favor the activation of the ALT mechanism versus telomerase in human tumorigenesis. In addition, the presence of an alternative mechanism of telomere maintenance raises the possibility that telomerase-positive tumors undergoing anti-telomerase therapies might escape by activating the ALT pathway. For these reasons, delineating the ALT mechanism is critical for our understanding of the tumorigenic process and the development of ALT-specific anti-neoplastic therapies. Recent studies have demonstrated that epigenetic modifications at telomeres have a profound effect on telomere length, and may also be linked to the ALT mechanism. In this review we focus on these recent advances and their implications in telomere maintenance.     

Chemotactic signaling,microglia, and Alzheimer's disease senile plaques: is there a connection?

Chemotactic cells known as microglia are involved in the inflammation associated with pathology in Alzheimer’s disease (AD). We investigate conditions that lead to aggregation of microglia and formation of local accumulations of chemicals observed in AD senile plaques. We develop a model for chemotaxis in response to a combination of chemoattractant and chemorepellent signaling chemicals. Linear stability analysis and numerical simulations of the model predict that periodic patterns in cell and chemical distributions can evolve under local attraction, long-ranged repulsion, and other constraints on concentrations and diffusion coefficients of the chemotactic signals. Using biological parameters from the literature, we compare and discuss the applicability of this model to actual processes in AD. Reprint address. Maternity leave.     

Chromatin: a connection between loops and barriers?

A genetic screen for proteins that can block the spread of silenced heterochromatin has identified components of the nuclear pores with potential barrier activity. These results suggest that formation of loops of chromatin anchored to the pore could be one mechanism of barrier function.     

Glycation,glycolysis, and neurodegenerative diseases: Is there any connection?

This review considers the interrelation between different types of protein glycation, glycolysis, and the development of amyloid neurodegenerative diseases. The primary focus is on the role of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase in changing the concentration of carbonyl compounds – first and foremost, glyceraldehyde-3-phosphate and methylglyoxal. It has been suggested that various modifications of the enzyme – from the oxidation of the sulfhydryl groups of the active site to glycation with sugars – can lead to its inactivation, which causes a direct increase in glyceraldehyde-3-phosphate concentration and an indirect increase in the content of other aldehydes. This “primary inactivation” of glyceraldehyde-3-phosphate dehydrogenase promotes its glycation with aldehydes, including its own substrate, and a further irreversible decrease in its activity. Such a cycle can lead to numerous consequences – from the induction of apoptosis, which is activated by modified forms of the enzyme, to glycation of amyloidogenic proteins by glycolytic aldehydes. Of particular importance during the inhibition of glyceraldehyde-3-phosphate dehydrogenase is an increase in the content of the glycating compound methylglyoxal, which is much more active than reducing sugars (glucose, fructose, and others). In addition, methylglyoxal is formed by two pathways – in the cascade of reactions during glycation and from glycolytic aldehydes. The ability of methylglyoxal to glycate proteins makes it the main participant in this protein modification. We consider the effect of glycation on the pathological transformation of amyloidogenic proteins and peptides – β-amyloid peptide, α-synuclein, and prions. Our primary focus is on the glycation of monomeric forms of these proteins with methylglyoxal, although most works are dedicated to the analysis of the presence of “advanced glycation end products” in the already formed aggregates and fibrils of amyloid proteins. In our opinion, the modification of aggregates and fibrils is secondary in nature and does not play an important role in the development of neurodegenerative diseases. The glycation of amyloid proteins with carbonyl compounds can be one of the triggers of their transformation into toxic forms. The possible role of glycation of amyloidogenic proteins in the prevention of their modification by ubiquitin and the SUMO proteins due to a disruption of their degradation is separately considered.     

Vegetable microbiomes: is there a connection among opportunistic infections,human health and our ‘gut feeling'?

The highly diverse microbiomes of vegetables are reservoirs for opportunistic and emerging pathogens. In recent years, an increased consumption, larger scale production and more efficient distribution of vegetables together with an increased number of immunocompromised individuals resulted in an enhanced number of documented outbreaks of human infections associated with the consumption of vegetables. Here we discuss the occurrence of potential pathogens in vegetable microbiomes, the impact of farming and processing practices, and plant and human health issues. Based on these results, we discuss the question if vegetables can serve as a source of infection for immunocompromised individuals as well as possible solutions to avoid outbreaks. Moreover, the potentially positive aspects of the vegetables microbiome for the gut microbiota and human health are presented.     

Landlocked Arctic charr (Salvelinus alpinus) population structure and lake morphometry in Greenland – is there a connection?

Landlocked Arctic charr (Salvelinus alpinus) populations in sub-Arctic and Arctic Greenland lakes were sampled with multi-mesh-sized survey gillnets. The study covered a range of small shallow lakes (0.01 km², maximum depth <3.3 m) to large deep lakes (43 km², maximum depth >200 m). Arctic charr were found in one to three different forms in lakes with maximum depths >3 m. A dwarf form occurred in all lakes inhabited by Arctic charr and was the only form in lakes with maximum depths <8 m. In deeper lakes with maximum depths >20 m and a surface area <0.5 km², larger charr were found, although in low numbers, the length-frequency distribution being unimodal with a tail towards large sizes. In lakes with a maximum depth >20 m, large-sized charr were more abundant, and the length-frequency distribution of the population was bimodal, with a first mode around 10–12 cm and a second mode around 26–37 cm. In a single large and deep lake, a distinct medium-sized pelagic zooplankton-eating charr form occurred. Maximum size of individual charr was significantly positively correlated with lake maximum depth and volume, and the mean size of large-sized charr was significantly positively correlated with lake volume. Our study indicates that the charr population structure became more complex with increasing lake size. Moreover, the population structure seemed to be influenced by lake-water transparency and the presence or absence of three-spined stickleback (Gasterosteus aculeatus). Accepted: 31 January 2000     

Is Helicobacter pylori a True Microaerophile?

BACKGROUND: There is no general consensus about the specific oxygen and carbon dioxide requirements of the human pathogen Helicobacter pylori. This bacterium is considered a microaerophile and consequently, it is grown under atmospheres at oxygen tensions 5-19% and carbon dioxide tensions 5-10%, both for clinical and basic and applied research purposes. The current study compared the growth of H. pylori in vitro, under various gas atmospheres, and determined some specific changes in the physiology of bacteria grown under different oxygen partial pressures. METHODS: Measurements of bacterial growth under various conditions were carried out employing classical solid and liquid culture techniques. Enzymatic activities were measured using spectrophotometric assays. RESULTS: H. pylori and all the other Helicobacter spp. tested had an absolute requirement for elevated carbon dioxide concentrations in the growth atmosphere. In contrast with other Helicobacter spp., H. pylori can tolerate elevated oxygen tensions when grown at high bacterial concentrations. Under 5% CO(2), the bacterium showed similar growth in liquid cultures under oxygen tensions from microaerobic (< 5%) to fully aerobic (21%) at cell densities higher than 5 x 10(5) cfu/ml for media supplemented with horse serum and 5 x 10(7) cfu/ml for media supplemented with beta-cyclodextrin. Evidence that changes occurred in the physiology of H. pylori was obtained by comparing the activities of ferredoxin:NADH (nicotinamide adenine dinucleotide) oxidoreductases of bacteria grown under microaerobic and aerobic atmospheres. CONCLUSIONS: H. pylori is a capnophile able to grow equally well in vitro under microaerobic or aerobic conditions at high bacterial concentrations, and behaved like oxygen-sensitive microaerophiles at low cell densities. Some characteristics of H. pylori cells grown in vitro under microaerobic conditions appeared to mimic better the physiology of organisms grown in their natural niche in the human stomach.     

Hormonal therapies and meningioma: Is there a link?

Background: The aetiology of meningiomas is largely unknown although hormones have been suggested to play a role. Methods: A cohort study was performed to evaluate hormone-related factors associated with meningioma. Patients (12–89 years) with a first diagnosis of meningioma (January 1996–June 2008) were identified from The Health Improvement Network UK primary care database and age- and sex-matched to controls (n = 10 000) from the same cohort. Odds ratios (ORs) were calculated following a nested case control analysis using unconditional logistic regression. Results: In total, 745 patients with meningioma were identified from a study population of 2 171 287. No significantly increased risk of meningioma was found among female users of oral contraceptives (OR: 1.15; CI: 0.67–1.98), hormone replacement therapy (OR: 0.99; CI: 0.73–1.35) or low-dose cyproterone acetate (CPA; OR: 1.51; CI: 0.33–6.86) compared with non-users. There was a significantly increased risk of meningioma among male users of androgen analogues (OR: 19.09; CI: 2.81–129.74) and among users of high-dose CPA (OR: 6.30; CI: 1.37–28.94) compared with non-users, however there were only three cases currently using these drugs. No significant association was found between meningioma and prostate, breast, or genital cancers. Conclusions: Our results do not support a role for exogenous hormone use by females in meningioma development. The risk in males was only observed with high-dose, short-term (<1 year) therapy. Impact: While hormonal cancers and therapies are not associated with meningioma in females, the risk in males requires further investigation.     

Is there a link between telomere maintenance and radiosensitivity?

Several recent studies point to the possibility that telomere maintenance may constitute a potential genetic marker of radiosensitivity. For example, the human diseases ataxia telangiectasia and Nijmegen breakage syndrome, which are characterized by clinical radiosensitivity, show alterations in telomere maintenance. In addition, Fanconi's anemia patients, who are characterized by mild cellular radiosensitivity and in some cases marked clinical radiosensitivity, have altered telomere maintenance. Similarly, a correlation between telomere maintenance and cellular radiosensitivity was reported in a group of breast cancer patients. Another study demonstrated that radiosensitivity may be more pronounced in human fibroblasts with short telomeres than in their counterparts with long telomeres. Several mouse models including mice deficient in Ku, DNA-PKcs (Prkdc), Parp and Atm, all of which are radiosensitive in vivo, show clear telomere alterations. The link between telomere maintenance and radiosensitivity is also apparent in mice genetically engineered to have dysfunctional telomeres. Finally, studies using non-mammalian model systems such as C. elegans and yeast point to the link between radiosensitivity and telomere maintenance. These results warrant further investigation to identify the extent to which these two phenotypes, namely radiosensitivity and telomere maintenance, are linked.