Association of Helicobacter pylori and gastric autoimmunity: A population-based study

Abstract Based on clinical studies, a negative association between Helicobacter pylori and autoimmune corpus gastritis is described. In the present investigation of an unselected population of 1461 adults we can state, however, that there exists a relationship between H. pylori infection and the development of gastric corpus autoimmunity. As confirmation for the gastric autoantibody development through molecular mimicry, a high homology (72% in 25 amino acid overlap) between the beta subunit of H. pylori urease and that of H + K + ATPase, the gastric parietal cell autoantigen, was revealed.     

Effect of tree species identity and related habitat parameters on understorey bryophytes – interrelationships between bryophyte,soil and tree factors in a 50-year-old experimental forest

Plant and Soil - Overstorey tree species influence both soil properties and microclimate conditions in the forest floor, which in turn can induce changes in ground bryophyte communities. The aim of...     

Conditional inactivation of the Cacna1a gene in transgenic mice

Ca(v)2.1 (P/Q-type) voltage-gated calcium channels play an important role in neurotransmitter release at many brain synapses and at the neuromuscular junction. Mutations in the CACNA1A gene, encoding the pore forming alpha(1) subunit of Ca(v)2.1 channels, are associated with a wide spectrum of neurological disorders. Here we generated mice with a conditional, floxed, Cacna1a allele without any overt phenotype. Deletion of the floxed Cacna1a allele resulted in ataxia, dystonia, and lethality during the fourth week, a severe phenotype similar to conventional Ca(v)2.1 knockout mice. Although neurotransmitter release at the neuromuscular junction was not affected in the conditional mice, homozygous deletion of the floxed allele caused an ablation of Ca(v)2.1 channel-mediated neurotransmission that was accompanied by a compensatory upregulation of Ca(v)2.3 (R-type) channels at this synapse. Pharmacological inhibition of Ca(v)2.1 channels is possible, but the contributing cell-types and time windows relevant to the different Ca(v)2.1-related neurological disorders can only be reliably determined using Cacna1a conditional mice.     

Radiation response of neural precursor cells: linking cellular sensitivity to cell cycle checkpoints, apoptosis and oxidative stress

Therapeutic irradiation of the brain can cause a progressive cognitive dysfunction that may involve defects in neurogenesis. In an effort to understand the mechanisms underlying radiation-induced stem cell dysfunction, neural precursor cells isolated from the adult rat hippocampus were analyzed for acute (0-24 h) and chronic (3-33 days) changes in apoptosis and reactive oxygen species (ROS) after exposure to X rays. Irradiated neural precursor cells exhibited an acute dose-dependent apoptosis accompanied by an increase in ROS that persisted over a 3-4-week period. The radiation effects included the activation of cell cycle checkpoints that were associated with increased Trp53 phosphorylation and Trp53 and p21 (Cdkn1a) protein levels. In vivo, neural precursor cells within the hippocampal dentate subgranular zone exhibited significant sensitivity to radiation. Proliferating precursor cells and their progeny (i.e. immature neurons) exhibited dose-dependent reductions in cell number. These reductions were less severe in Trp53-null mice, possibly due to the disruption of apoptosis. These data suggest that the apoptotic and ROS responses may be tied to Trp53-dependent regulation of cell cycle control and stress-activated pathways. The temporal coincidence between in vitro and in vivo measurements of apoptosis suggests that oxidative stress may provide a mechanistic explanation for radiation-induced inhibition of neurogenesis in the development of cognitive impairment.     

IgG from patients with liver diseases inhibit mitochondrial respiration in permeabilized oxidative muscle cells: Impaired function of intracellular energetic units?

The effect of IgG purified from the sera of healthy persons and patients with primary biliary cirrhosis (PBC) and chronic hepatitis (CH) on ADP dependent respiration (oxidative phosphorylation) in skinned muscle fibers from rat oxidative muscles (heart and M. soleus) and glycolytic skeletal muscle (M. gastrocnemius) was studied. The results show that IgG from three different sources inhibited the rate of respiration by 13, 44 and 42%, respectively, these effects being equally expressed in both types of oxidative muscles, whereas no inhibition was observed in glycolytic muscle. The following washout of unbound IgG did not abolish the inhibition of respiration suggesting that the specific interaction of IgG with antigens had taken place. Laser confocal analysis revealed binding of IgG predominantly to the sarcomeric structures such as Z-disk and M-lines in the cardiomyocytes. The staining of IgG within Z-disks and intermitochondrial space coincided throughout the muscle cells so that transversally serial spaces, each containing mitochondria and adjacent sarcomere, became clearly visible. When the IgG from a CH patient was incubated with the skinned myocardial fibers of the desmin knockout mice, its binding to Z-disks and the sarcomeric area was found to be similar to that in normal cardiac muscle. However, the transversal staining pattern was disintegrated, because of the slippage of the myofibrils in relation to each other and accumulation of mitochondria between them. These observations support the recent hypothesis that in oxidative muscles the mitochondria and adjacent sarcomeres form complexes, termed as the intracellular energetic units, ICEUs. Moreover, they indicate that human autoantibodies can be useful tools for localizing the proteins responsible for formation of ICEUs and modulation of their function. Thus, it appears that the proteins associated with the Z-disks and M-lines may participate in formation of ICEUs and that binding of IgG to these proteins decreases the access of exogenous adenine nucleotides to mitochondria, which manifests as decreased rate of ADP-dependent respiration.     

Non-medical treatments and their outcomes

This article focuses on outcomes of Spiritualist treatments based upon a series of follow-up studies of patients who came to a Spiritualist temple situated in a rural region of Mexico. Categories of temple patients and conditions under which they resort to alternate therapeutic regimes are also examined. Follow-ups reveal that Spiritualist healers fail more than they succeed in treating their patients. The data suggest that therapeutic benefits from Spiritualist healing tend to occur in four types of disorders — simple diarrheas, simple gynecological disorders, somatized syndromes and minor psychiatric disorders. The findings suggest that successful treatment outcomes are effected not only by concrete manipulation of physiological symptoms but by symbolic manipulation as well. That is, for a therapeutic regime to do its job it must confront cultural imperatives and employ cultural symbols relevant to the removal of the sick role. An unexpected finding of the study reveals that, in the Mexican case, the cultural imperatives relate to cleaning and purification, mediated by tactile communication, which serve symbolically to terminate the sick role.Eastern Michigan UniversityI very gratefully acknowledge the support from the National Science Foundation (Grant # BNS 77 13980) for this research and I am particularly thankful to Vivian Garrison and Arthur Kleinman for their very valuable comments.