Catalase enzyme mutations and their association with diseases.

Enzyme catalase seems to be the main regulator of hydrogen peroxide metabolism. Hydrogen peroxide at high concentrations is a toxic agent, while at low concentrations it appears to modulate some physiological processes such as signaling in cell proliferation, apoptosis, carbohydrate metabolism, and platelet activation. Benign catalase gene mutations of 5' noncoding region (15) and intron 1 (4) have no effect on catalase activity and are not associated with disease.Catalase gene mutations have been detected in association with diabetes mellitus, hypertension, and vitiligo. Decreases in catalase activity in patients with tumors is more likely to be due to decreased enzyme synthesis rather than to catalase mutations.Acatalasemia, the inherited deficiency of catalase has been detected in 11 countries. Its clinical features might be oral gangrene, altered lipid, carbohydrate, homocysteine metabolism and the increased risk of diabetes mellitus. The Japanese, Swiss, and Hungarian types of acatalasemia display differences in biochemical and genetic aspects. However, there are only limited reports on the syndrome causing these mutations.These data show that acatalasemia may be a syndrome with clinical, biochemical, genetic characteristics rather than just a simple enzyme deficiency.     

Review of nocardial infections in France 1987 to 1990

On the basis of the numbers ofNocardia strains referred to the National Reference Center for Mycoses and Antifungal Agents (NRC), Institut Pasteur, Paris, in the period from 1987 to 1990, it was estimated that between 150 and 250 cases of nocardiosis are diagnosed in France each year. A total of 63 clinical isolates were referred to the NRC and identified asNocardia asteroides (66.7 %),Nocardia farcinica (23.8 %),Nocardia brasiliensis (3.2 %),Nocardia otitidiscaviarum (4.8 %) andNocardia carnea (1.5 %).Nocardia asteroides accounted for 71.4 % of pulmonary infections, 80.0 % of central nervous system infections and 80.0 % of systemic infections. Patients infected withNocardia farcinica died in 57.1 % of cases, compared with 17.6 % of patients infected withNocardia asteroides. Corticosteroid therapy represented a significant factor in mortality. Isolates ofNocardia asteroides revealed variable resistance, whereas isolates ofNocardia farcinica were resistant to most antimicrobial agents. Only amoxicillin/clavulanic acid, imipenem, cefoxitin, kanamycin, amikacin, minocycline and vancomycin showed activity against both species. Nocardiosis caused byNocardia farcinica may be a growing problem because of the relatively high incidence in AIDS patients and the resistance of this species to most antimicrobial agents.     

Splice variants of the relaxin and INSL3 receptors reveal unanticipated molecular complexity

LGR7 and LGR8 are G protein-coupled receptors that belong to the leucine-rich repeat-containing G-protein coupled receptor (LGR) family, including the thyroid-stimulating hormone (TSH), LH and FSH receptors. LGR7 and LGR8 stimulate cAMP production upon binding of the cognate ligands, relaxin and insulin-like peptide 3 (INSL3), respectively. We cloned several novel splice variants of both LGR7 and LGR8 and analysed the function of four variants. LGR7.1 is a truncated receptor, including only the N-terminal region of the receptor and two leucine rich repeats. In contrast, LGR7.2, LGR7.10 and LGR 8.1 all contain an intact seven transmembrane domain and most of the extracellular region, lacking only one or two exons in the ectodomain. Our analysis demonstrates that although LGR7.10 and LGR8.1 are expressed at the cell surface, LGR7.2 is predominantly retained within cells and LGR7.1 is partially secreted. mRNA expression analysis revealed that several variants are co-expressed in various tissues. None of these variants were able to stimulate cAMP production following relaxin or INSL3 treatment. Unexpectedly, we did not detect any direct specific relaxin or INSL3 binding on any of the splice variants. The large number of receptor splice variants identified suggests an unforeseen complexity in the physiology of this novel hormone-receptor system.     

Monoclonal anti-nucleoside antibodies. Characterization and application in an enzyme immunoassay of single-stranded DNA

Two mouse monoclonal antibodies were raised against adenosine and guanosine coupled to bovine serum albumin (BSA) by periodate oxidation. They were named A-16 and G-K21 respectively and selected for their ability to recognize single-stranded DNA. Their epitope specificities were assessed and their dissociation constants determined by an indirect ELISA method. The KD values for adenosine and guanosine coupled to BSA were 9.9 X 10(-7) M and 1.1 X 10(-10) M for G-K21 respectively, and 2.5 X 10(-8) M and 1.0 X 10(-6) M for A-16. These monoclonal anti-nucleoside antibodies were used to develop a sandwich enzyme immunoassay for single-stranded DNA. The purified IgG antibodies were coupled to beta-galactosidase and alkaline phosphatase by the one-step glutaraldehyde method and used in a test optimized for pH, saturating proteins, coating antibody, nature of the conjugate and protein concentrations. Less than 100 pg/well of single-stranded DNA could be detected, and the detection was linear over a DNA concentration ranging from 0.34 to 34 ng/ml. The assay could quantitate single-stranded DNAs of differing origin, but not RNAs. The test was compared to another titration method, and used to calibrate target DNA amounts in non-radioactive hybridization experiments.     

Tuberous breast syndrome. Report on a series of 22 operated patients

The tuberous breast syndrome is a rare unilateral or bilateral breast malformation presenting at the age of mammary development. It requires surgical correction, depending on the severity of the clinical expression, because of its inaesthetic appearance. We report a series of 22 patients (35 breasts) treated and followed up in the plastic and reconstructive surgery department of Rennes over a period of nearly ten years. The average age was 18 +/- 3.2 years (range: 15-26 years old). Long-term results were assessed by the surgical team and the patients on the basis of objective and subjective criteria with an average follow-up of 36 months (12 to 116 months). In our opinion, surgical correction should be proposed after puberty with, whenever possible, section of the basal fibrous ring and glandular plasty via a periareolar incision. The use of mammary implant alone or in combination with breast tissue remodelling must be reserved for hypoplastic cases only.     

In Utero and Childhood Polybrominated Diphenyl Ether Exposures and Body Mass at Age 7 Years: The CHAMACOS Study

Background

Polybrominated diphenyl ethers (PBDEs) are lipophilic flame retardants that bioaccumulate in humans. Child serum PBDE concentrations in California are among the highest worldwide. PBDEs may be associated with obesity by disrupting endocrine systems.

Objective

In this study, we examined whether pre- and postnatal exposure to the components of pentaBDE mixture was associated with childhood obesity in a population of Latino children participating in a longitudinal birth cohort study in the Salinas Valley, California.

Methods

We measured PBDEs in serum collected from 224 mothers during pregnancy and their children at 7 years of age, and examined associations with body mass index (BMI) at age 7 years.

Results

Maternal PBDE serum levels during pregnancy were associated with higher BMI z-scores in boys (BMI z-score β_adjusted = 0.26; 95% CI: –0.19, 0.72) but lower scores in girls (BMI z-score β_adjusted = –0.41; 95% CI: –0.87, –0.05) at 7 years of age (p_interaction = 0.04). In addition, child’s serum BDE-153 concentration (log₁₀), but not other pentaBDE congeners, demonstrated inverse associations with BMI at age 7 years (BMI z-score β_adjusted = –1.15; 95% CI: –1.53, –0.77), but there was no interaction by sex.

Conclusions

We estimated sex-specific associations with maternal PBDE levels during pregnancy and BMI at 7 years of age, finding positive associations in boys and negative associations in girls. Children’s serum BDE-153 concentrations were inversely associated with BMI at 7 years with no difference by sex. Future studies should examine the longitudinal trends in obesity with PBDE exposure and changes in hormonal environment as children transition through puberty, as well as evaluate the potential for reverse causality.

Citation

Erkin-Cakmak A, Harley KG, Chevrier J, Bradman A, Kogut K, Huen K, Eskenazi B. 2015. In utero and childhood polybrominated diphenyl ether exposures and body mass at age 7 years: the CHAMACOS Study. Environ Health Perspect 123:636–642; http://dx.doi.org/10.1289/ehp.1408417     

Interspecies comparison of subchondral bone properties important for cartilage repair

Microfracture repair tissue in young adult humans and in rabbit trochlea is frequently of higher quality than in corresponding ovine or horse models or in the rabbit medial femoral condyle (MFC). This may be related to differences in subchondral properties since repair is initiated from the bone. We tested the hypothesis that subchondral bone from rabbit trochlea and the human MFC are structurally similar. Trochlea and MFC samples from rabbit, sheep, and horse were micro‐CT scanned and histoprocessed. Samples were also collected from normal and lesional areas of human MFC. The subchondral bone of the rabbit trochlea was the most similar to human MFC, where both had a relatively thin bone plate and a more porous and less dense character of subchondral bone. MFC from animals all displayed thicker bone plates, denser and less porous bone and thicker trabeculae, which may be more representative of older or osteoarthritic patients, while both sheep trochlear ridges and the horse lateral trochlea shared some structural features with human MFC. Since several cartilage repair procedures rely on subchondral bone for repair, subchondral properties should be accounted for when choosing animal models to study and test procedures that are intended for human cartilage repair. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:63–70, 2015.

     

Role for Streptococcal Collagen-Like Protein 1 in M1T1 Group A Streptococcus Resistance to Neutrophil Extracellular Traps

Streptococcal collagen-like protein 1 (Scl-1) is one of the most highly expressed proteins in the invasive M1T1 serotype group A Streptococcus (GAS), a globally disseminated clone associated with higher risk of severe invasive infections. Previous studies using recombinant Scl-1 protein suggested a role in cell attachment and binding and inhibition of serum proteins. Here, we studied the contribution of Scl-1 to the virulence of the M1T1 clone in the physiological context of the live bacterium by generating an isogenic strain lacking the scl-1 gene. Upon subcutaneous infection in mice, wild-type bacteria induced larger lesions than the Δscl mutant. However, loss of Scl-1 did not alter bacterial adherence to or invasion of skin keratinocytes. We found instead that Scl-1 plays a critical role in GAS resistance to human and murine phagocytic cells, allowing the bacteria to persist at the site of infection. Phenotypic analyses demonstrated that Scl-1 mediates bacterial survival in neutrophil extracellular traps (NETs) and protects GAS from antimicrobial peptides found within the NETs. Additionally, Scl-1 interferes with myeloperoxidase (MPO) release, a prerequisite for NET production, thereby suppressing NET formation. We conclude that Scl-1 is a virulence determinant in the M1T1 GAS clone, allowing GAS to subvert innate immune functions that are critical in clearing bacterial infections.