<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.     

Eradication of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> Infection

Helicobacter pylori infects about 50 % of the world’s population, causing at a minimum chronic gastritis. A subset of infected patients will ultimately develop gastric or duodenal ulcer disease, gastric adenocarcinoma, or MALT (mucosa-associated lymphoid tissue) lymphoma. Eradication of H. pylori requires complex regimens that include acid suppression and multiple antibiotics. The efficacy of treatment using what were once considered standard regimens have declined in recent years, mainly due to widespread development of antibiotic resistance. Addition of bismuth to standard triple therapy regimens, use of alternate antibiotics, or development of alternative regimens using known therapies in novel combinations have improved treatment efficacy in specific populations, but overall success of eradication remains less than ideal. Novel regimens under investigation either in vivo or in vitro, involving increased acid suppression ideally with fewer antibiotics or development of non-antibiotic treatment targets, show promise for future therapy.     

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.     

Gastric Infection by <Emphasis Type="Italic">Helicobacter pylori</Emphasis>

Helicobacter pylori infects half of the world’s population and plays a causal role in ulcer disease and gastric cancer. This pathogenic neutralophile uniquely colonizes the acidic gastric milieu through the process of acid acclimation. Acid acclimation is the ability of the organism to maintain periplasmic pH near neutrality in an acidic environment to prevent a fall in cytoplasmic pH in order to maintain viability and growth in acid. Recently, due to an increase in antibiotic resistance, the rate of H. pylori eradication has fallen below 80% generating renewed interest in novel eradication regimens and targets. In this article, we review the gastric biology of H. pylori and acid acclimation, various detection procedures, antibiotic resistance and the role that gastric acidity plays in the susceptibility of the organism to antibiotics currently in use and propose several novel drug targets that would promote eradication in the absence of antibiotics.     

<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">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.     

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.     

<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.     

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.     

Coughing Precipitated by <Emphasis Type="Italic">Bordetella pertussis</Emphasis> Infection

Infections with the gram-negative bacteria Bordetella pertussis (B. pertussis) have long been recognized as a significant threat to children and are increasingly recognized as a cause of cough in adolescents and adults. Antibiotic therapy, when administered during the virulent stages of the disease, can reduce the duration and severity of symptoms. Unfortunately, there are no effective treatments for the persistent coughing that accompanies and follows the infection. The pathogenesis of B. pertussis infection is briefly reviewed. Also discussed is the evidence supporting the hypothesis that the inflammatory peptide bradykinin may be responsible for the persistent, paroxysmal coughing associated with B. pertussis-initiated illness.     

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.     

Cardiovascular Concerns in <Emphasis Type="Italic">BRCA1</Emphasis> and <Emphasis Type="Italic">BRCA2</Emphasis> Mutation Carriers

Purpose of review

BRCA1 and BRCA2 mutation carriers can be at increased cardiovascular risk. The goal of this review is to provide information about factors associated with increased cardiovascular risk, methods to prevent cardiovascular toxicities, and recommended screening guidelines.

Recent findings

BRCA1/2 mutation carriers who are diagnosed with cancer are often exposed to chemotherapy, chest radiotherapy, and/or HER2 directed therapies, all of which can be cardiotoxic. In addition, BRCA1/2 carriers often undergo prophylactic salpingoopherectomies, which may also increase cardiovascular risks.

Summary

Understanding the potential for increased cardiovascular risk in individuals with a BRCA1 or BRCA2 mutation, as well as gold standard practices for prevention, detection, and treatment of cardiac concerns in this population, is important.

     

Joint effects of HLA, <Emphasis Type="Italic">INS</Emphasis>, <Emphasis Type="Italic">PTPN22</Emphasis> and <Emphasis Type="Italic">CTLA4</Emphasis> genes on the risk of type 1 diabetes

Background/hypothesis HLA, INS, PTPN22 and CTLA4 are considered to be confirmed type 1 diabetes susceptibility genes. HLA, PTPN22 and CTLA4 are known to be involved in immune regulation. Few studies have systematically investigated the joint effect of multiple genetic variants. We evaluated joint effects of the four established genes on the risk of childhood-onset type 1 diabetes. Methods We genotyped 421 nuclear families, 1,331 patients and 1,625 controls for polymorphisms of HLA-DRB1, −DQA1 and −DQB1, the insulin gene (INS, −23 HphI), CTLA4 (JO27_1) and PTPN22 (Arg620Trp). Results The joint effect of HLA and PTPN22 on type 1 diabetes risk was significantly less than multiplicative in the case-control data, but a multiplicative model could not be rejected in the trio data. All other two-way gene–gene interactions fitted multiplicative models. The high-risk HLA genotype conferred a very high risk of type 1 diabetes (OR 20.6, using the neutral-risk HLA genotype as reference). When including also intermediate-risk HLA genotypes together with risk genotypes at the three non-HLA loci, the joint odds ratio was 61 (using non-risk genotypes at all loci as reference). Conclusion Most established susceptibility genes seem to act approximately multiplicatively with other loci on the risk of disease except for the joint effect of HLA and PTPN22. The joint effect of multiple susceptibility loci conferred a very high risk of type 1 diabetes, but applies to a very small proportion of the general population. Using multiple susceptibility genotypes compared with HLA genotype alone seemed to influence the prediction of disease only marginally. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.