Linezolid-Resistant <Emphasis Type="Italic">Enterococcus faecium</Emphasis> and <Emphasis Type="Italic">Enterococcus faecalis</Emphasis> Isolated from a Septic Patient: Report of First Isolates in Germany

Abstract. Here we report the first German case of necrotizing pancreatitis, peritonitis, and septic shock caused by linezolid-resistant Enterococcus faecium and Enterococcus faecalis.     

Molecular epidemiology of <Emphasis Type="Italic">Enterococcus faecium</Emphasis> isolates from an Italian hospital

Background  

Outbreaks of vancomycin-resistant Enterococcus faecium (VRE) strains is an emerging problem worldwide. Even if still relatively uncommon in European hospitals, infections caused by VRE have also been increasing recently in this continent.     

<Emphasis Type="Italic">T-</Emphasis>Scores and <Emphasis Type="Italic">Z</Emphasis>-Scores

Bone mineral density (BMD) can be measured by a variety of techniques at several skeletal sites. Once measured, the manufacturers’ software uses the BMD to calculate a T-score and/or Z-score. Both T-scores and Z-scores are derived by comparison to a reference population on a standard deviation scale. The recommended reference group for the T-score is a young gender-matched population at peak bone mass, while the Z-score should be derived from an age-matched reference population. T-scores and Z-scores are widely quoted in scientific publications on osteoporosis and BMD studies, and are the values used for DXA diagnostic criteria and current clinical guidelines for the management of osteoporosis. Errors in BMD measurement, differences in reference populations, and variations in calculation methods used, can all affect the actual T-score and Z-score value. Attempts to standardize these values have made considerable progress, but inconsistencies remain within and across BMD technologies. This can be a source of confusion for clinicians interpreting BMD results. A clear understanding of T-scores and Z-scores is essential for correct interpretation of BMD studies in clinical practice.     

Association of <Emphasis Type="Italic">Lewis</Emphasis> and <Emphasis Type="Italic">Secretor</Emphasis> gene polymorphisms and <Emphasis Type="Italic">Helicobacter pylori</Emphasis> seropositivity among Japanese-Brazilians

Background Secretor (Se) and Lewis (Le) genes are involved in the synthesis of Lewis b (Le^b) and type I antigens throughout the body, especially in the epithelial cells of gastric mucosa. Helicobacter pylori can attach to the gastric epithelial cells with the blood group antigen-binding adhesin, which binds to Le^b or H type I carbohydrate structures. In a previous study, a marked association between H. pylori seropositivity and polymorphism of the Se and Le genes was observed among Japanese outpatients of a gastroenterology clinic. The present work aims to investigate the associations between Se and Le gene polymorphisms and H. pylori infection among Japanese-Brazilians.Methods The subjects consisted of 942 healthy volunteer Japanese-Brazilians, who were tested for the presence of anti-H. pylori IgG antibodies and genotyped for Se and Le polymorphisms.Results The sex-age-adjusted odds ratios (aORs) for H. pylori seropositivity were 0.99 for the Sese genotype relative to the SeSe genotype (95% confidence interval [CI], 0.73–1.33), and 1.03 for sese relative to SeSe (95% CI, 0.71–1.48). On the other hand, the aOR for the subjects with the le allele (Lele or lele) relative to the LeLe genotype was 1.48 (95% CI, 1.07–1.79). When the Se and Le genotypes were analyzed in combination according to risk group, no statistically significant association was observed.Conclusions These results are inconsistent with previous work and may have been modulated by an external factor or some other unidentified factor. Japanese-Brazilians are genotypically the same as Japanese, but their lifestyle is adapted to that of Brazil. Further investigations are necessary to clarify this influence on susceptibility to H. pylori infection.     

<Emphasis Type="Italic">Anisakis</Emphasis> spp. burden in <Emphasis Type="Italic">Trachurus trachurus</Emphasis>

Anisakis is a parasite of marine mammals that uses a great number of fish species as intermediate or paratenic hosts. It is common in commercially important marine fishes and its presence is of great concern for both human health and economic reasons. Horse mackerels (Trachurus trachurus) originated from the Northern Aegean Sea were examined for the presence of Anisakis spp. larvae. The prevalence of Anisakis spp. was found 98.8 %. The number of parasites was significantly related to the host’s length but was not related to the fish gender. The month of sampling affected the size of the fishes and consequently the number of parasites. The length of larvae was not related to the host’s length. The present study resulted in the design of a prediction model for the number of existing parasites in the fish by measuring only its Fixed Length.     

<Emphasis Type="Italic">Gcg</Emphasis><Superscript><Emphasis Type="Italic">CreERT2</Emphasis></Superscript> knockin mice as a tool for genetic manipulation in pancreatic alpha cells

Aims/hypothesis

The Cre/loxP system, which enables tissue-specific manipulation of genes, is widely used in mice for diabetes research. Our aim was to develop a new Cre-driver mouse line for the specific and efficient manipulation of genes in pancreatic alpha cells.

Methods

A Gcg ^CreERT2 knockin mouse, which expresses a tamoxifen-inducible form of Cre from the endogenous preproglucagon (Gcg) gene locus, was generated by homologous recombination. The new Gcg ^CreERT2 mouse line was crossed to the Rosa26 ^tdTomato (R26 ^tdTomato ) Cre reporter mouse line in order to evaluate the tissue specificity, efficiency and tamoxifen dependency of Gcg ^CreERT2 -mediated recombination. Cell types of pancreatic islets were identified using immunohistochemistry. Biochemical and physiological data, including blood glucose levels, plasma glucagon and glucagon-like peptide (GLP)-1 levels, and pancreatic glucagon content, were collected and used to assess the overall effect of Gcg gene targeting on Gcg ^CreERT2/w heterozygous mice.

Results

Tamoxifen-treated Gcg ^CreERT2/w ;R26 ^tdTomato/w mice displayed Cre reporter activity, i.e. expression of tdTomato red fluorescent protein (RFP) in all known cells that produce proglucagon-derived peptides. In the adult pancreas, RFP was detected in 94–97% of alpha cells, whereas it was detected in a negligible (~ 0.2%) proportion of beta cells. While more than 98% of cells labelled with tamoxifen-induced RFP were glucagon-positive cells, 14–25% of pancreatic polypeptide (PP)-positive cells were also positive for RFP, indicating the presence of glucagon/PP bihormonal cell population. Tamoxifen-independent expression of RFP occurred in approximately 6% of alpha cells. In contrast to alpha cells and GLP-1-producing neurons, in which RFP expression persisted for at least 5 months after tamoxifen administration (presumably due to rare neogenesis in these cell types in adulthood), nearly half of RFP-positive intestinal L cells were replaced with RFP-negative L cells over the first 2 weeks after tamoxifen administration. Heterozygous Gcg ^CreERT2/w mice showed reduced Gcg mRNA levels in islets, but maintained normal levels of pancreatic and plasma glucagon. The mice did not exhibit any detectable baseline physiological abnormalities, at least in young adulthood.

Conclusions/interpretation

The newly developed Gcg ^CreERT2 knockin mouse shows faithful expression of CreER^T2 in pancreatic alpha cells, intestinal L cells and GLP-1-producing neurons. This mouse line will be particularly useful for manipulating genes in alpha cells, due to highly specific and efficient CreER^T2-mediated recombination in this cell type in the pancreas.

     

<Emphasis Type="Italic">Aspergillus</Emphasis> and <Emphasis Type="Italic">Penicillium</Emphasis> allergens: Focus on proteases

Penicillium and Aspergillus species are prevalent airborne fungi. It is imperative to identify and characterize their major allergens. Alkaline and/or vacuolar serine proteases are major allergens of several prevalent Penicillium and Aspergillus species. They are also major immunoglobulin (Ig) E-reacting components of the most prevalent airborne yeast, Rhodotorula mucilaginosa, and the most prevalent Cladosporium species, C. cladosporioides. IgE cross-reactivity has been detected among these major pan-fungal serine protease allergens. In addition, the alkaline serine protease of P. chrysogenum (Pen ch 13) induces histamine release from basophils of asthmatic patients, degrades the tight junction protein occludin, and stimulates release of proinflammatory mediators from human bronchial epithelial cells. In addition to induction of IgE and inflammatory airway responses, the alkaline serine protease allergen of A. fumigatus (Asp f 13) has synergistic effects on Asp f 2-induced immune response in mice. Studies of these serine protease major allergens elucidate the diverse allergic disease mechanisms and facilitate the development of better therapeutic strategies.     

Increase of <Emphasis Type="Italic">Drosophila melanogaster</Emphasis> lifespan due to <Emphasis Type="Italic">D</Emphasis>-<Emphasis Type="Italic">GADD45</Emphasis> overexpression in the nervous system

The GADD45 protein family plays an important role in stress signaling and participates in the integration of cellular response to environmental and physiological factors. GADD45 proteins are involved in cell cycle control, DNA repair, apoptosis, cell survival and aging, and inflammatory response by complicated protein–protein interactions. In Drosophila melanogaster a single D-GADD45 ortholog (GG1086) has been described. Our data show that overexpression of the D-GADD45 gene in the nervous system leads to a significantly increase of Drosophila lifespan without a decrease in fecundity and locomotor activity. The lifespan extension effect is more pronounced in males than in females, which agrees with the sex-dependent expression of this gene. The longevity of D. melanogaster with D-GADD45 overexpression is apparently due to more efficient recognition and repair of DNA damage, as the DNA comet assay showed that the spontaneous DNA damage in the larva neuroblasts is reduced with statistical significance.     

<Emphasis Type="Italic">hSNF5</Emphasis><Emphasis Type="Italic">/INI1</Emphasis> mutation analysis in acute myeloid leukemia

Previous studies indicated that region 11.2 of the long arm of chromosome 22 (22q11.2) might be a locus encoding a tumor suppressor gene, since its deletion is a recurrent genetic characteristic of aggressive pediatric cancer. This region is found in the human immunodeficiency virus integrase interactor 1 (hSNF5/INI1) gene. To investigate whether the hSNF5/INI1 gene is involved in leukemogenesis, mutation analysis of the hSNF5/INI1 gene was performed in the present study using 5 hematopoietic cell lines, acute myeloid leukemia (AML) specimen and normal control. We found two single nucleotide polymorphisms at the hSNF5/INI1 gene in exon 4 and exon 9. The results of this study suggest that the hSNF5/INI1 gene does not play an important role in the leukemogenesis of AML.     

Coexistent Rearrangements of c-<Emphasis Type="Italic">MYC</Emphasis>,<Emphasis Type="Italic">BCL2</Emphasis>, and<Emphasis Type="Italic">BCL6</Emphasis> Genes in a Diffuse Large B-Cell Lymphoma

We present a patient with stage III de novo diffuse large B-cell lymphoma. The lymphoma cells showed mature B-cell immunophenotype but lacked surface immunoglobulin (Ig) expression. Long-distance and long-distance inverse polymerase chain reaction assays to detect the oncogene/Ig gene rearrangement revealed that the cells carried 3 independent fusion genes, namely, c-MYC/Ig heavy chain gene (IgH), BCL2/IgH, and Ig lambda light chain gene/BCL6. Thus, the lymphoma cells concurrently carried t(8;14)(q24;q32), t(14;18)(q32;q21), and t(3;22)(q27;q11), which developed in association with class switching, V/D/J recombination, and somatic hypermutation, respectively. The lymphoma responded to chemoradiotherapy, and the patient has been well for 2 years, suggesting that multiple oncogene rearrangements may not necessarily be associated with poor clinical outcome.     

Epigenetic factors Polycomb (<Emphasis Type="Italic">Pc</Emphasis>) and Suppressor of zeste (<Emphasis Type="Italic">Su</Emphasis>(<Emphasis Type="Italic">z</Emphasis>)2) negatively regulate longevity in <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

The process of aging is a hallmark of the natural life span of all organisms and individuals within a population show variability in the measures of age related performance. Longevity and the rate of aging are influenced by several factors such as genetics, nutrition, stress, and environment. Many studies have focused on the genes that impact aging and there is increasing evidence that epigenetic factors regulate these genes to control life span. Polycomb (PcG) and trithorax (trxG) protein complexes maintain the expression profiles of developmentally important genes and regulate many cellular processes. Here, we report that mutations of PcG and trxG members affect the process of aging in Drosophila melanogaster, with perturbations mostly associated with retardation in aging. We find that mutations in polycomb repressive complex (PRC1) components Pc and Su(z)2 increase fly survival. Using an inducible UAS-GAL4 system, we show that this effect is tissue-specific; knockdown in fat body, but not in muscle or brain tissues, enhances life span. We hypothesize that these two proteins influence life span via pathways independent of their PRC1 functions, with distinct effects on response to oxidative stress. Our observations highlight the role of global epigenetic regulators in determining life span.     

<Emphasis Type="Italic">Mycoplasma genitalium</Emphasis>

Mycoplasma genitalium was initially isolated from men with nongonococcal urethritis in 1980. Subsequent studies to assess the association of M. genitalium with human disease were inhibited however because on repeated attempts the organism proved extremely difficult to culture. Fortunately, the development and use of specific polymerase chain reaction assays allowed progress in this arena and provided evidence of the association between M. genitalium and urethritis, cervicitis, and endometritis. A serologic association has also been noted between M. genitalium antibody and salpingitis and tubal factor infertility. In addition, sexual transmission of M. genitalium in heterosexual partners has also been demonstrated. Currently, studies are underway to further assess these associations and provide additional information about the significance of this organism with regards to sexual transmission, infertility in women, and its association with other genital tract disease processes. Recent studies have suggested that M. genitalium-associated infections are best treated with azithromycin.     

An update on the geohelminths: <Emphasis Type="Italic">Ascaris lumbricoides</Emphasis>, hookworms, <Emphasis Type="Italic">Trichuris trichiura</Emphasis>, and <Emphasis Type="Italic">Strongyloides stercoralis</Emphasis>

Geohelminths remain prevalent throughout the developing world where levels of sanitation, personal hygiene, and maternal education are low. The five species of nematodes responsible for the bulk of disease are Ascaris lumbricoides, the hookworms Ancylostoma duodenale and Necator americanus, Trichuris trichiura, and Strongyloides stercoralis. Geohelminths are acquired through ingestion of fecally contaminated food or water or through contact with infected soil. In developing countries, infection with more than one nematode species and high worm burdens are common. The morbidity is substantial, particularly among children, and deaths occur. Geohelminthic infections are encountered in industrialized countries among immigrants and long-term travelers who have lived in endemic regions where sanitation is poor, and occasionally following autochthonous transmission.     

Congenital Hyperinsulinism due to mutations in <Emphasis Type="Italic">HNF4A</Emphasis> and <Emphasis Type="Italic">HADH</Emphasis>

Mutations in the HADH and HNF4A genes are rare causes of diazoxide responsive congenital hyperinsulinism (CHI). This chapter details the phenotype known to be associated with mutations in these genes. Additionally, the authors give a brief overview of the role of these genes in glucose physiology and the possible mechanisms of CHI in patients with mutations in these genes.