Phenotypic and genotypic characterization of prolyliminopeptidase-negative Neisseria gonorrhoeae isolates in Denmark

In the study presented here 26 recent Danish clinical isolates of prolyliminopeptidase (PIP)-negative Neisseria gonorrhoeae were phenotypically and genotypically characterized to investigate whether one or more PIP-negative strains are circulating in the Danish community. The profiles of these isolates were compared with those of three isolates from a recent outbreak of PIP-negative N. gonorrhoeae infection in the UK. Twenty-five of the Danish isolates and all three UK isolates had similar antibiograms and were designated serovar IB-4. Genotypic characterization by pulsed-field gel electrophoresis, porB1b gene sequencing, and opa-typing revealed that these isolates were indistinguishable or closely related. The results indicate that at least one PIP-negative N. gonorrhoeae strain is currently circulating in the Danish community, and this strain is indistinguishable from the one that caused an outbreak in the UK.An erratum to this article can be found at     

A prospective study of fatal occupational accidents -- relationship to sleeping difficulties and occupational factors

Very little is known about the association between sleep and (fatal) occupational accidents. This study investigated this relationship using register data of self-rated sleep difficulties, together with occupational and demographic characteristics. The variables were related to subsequent occupational fatal accidents. A national sample of 47,860 individuals was selected at regular intervals over a period of 20 years, and interviewed over the phone on issues related to work and health. The responses were linked to the cause of death register (suicides excluded) and the data set was subjected to a (multivariate) Cox regression survival analysis. One hundred and sixty six fatal occupational accidents occurred, and the significant predictors were: male vs. female: relative risk (RR)=2.30 with a 95% confidence interval (CI) of 1.56-3.38; difficulties in sleeping (past 2 weeks): RR=1.89 with CI=1.22-2.94; and non-day work: RR=1.63 with CI=1.09-2.45. No significant effect was seen for age, socio-economic group, hectic work, overtime (>50 h per week), or physically strenuous work. It was concluded that self-reported disturbed sleep is a predictor of accidental death at work, in addition to non-day work and male gender.     

Peroxiredoxins in breast carcinoma.

PURPOSE: Peroxiredoxins (Prxs) are a novel group of peroxidases containing high antioxidant efficiency and some of them having also effects on cell differentiation and apoptosis. The mammalian Prx family has six distinct members located in various subcellular locations, including peroxisomes and mitochondria, places where oxidative stress is most evident. EXPERIMENTAL DESIGN: We examined immunohistochemically a large set of samples from patients with breast carcinoma and investigated associations with parameters such as tumor-node-metastasis classification, hormone receptor status, and patient survival. Three biopsies of healthy breast tissue were used as controls. RESULTS: Expression of peroxiredoxins I, III, IV, and V was found in >or=80% of cases, whereas the expression of Prx II and VI was less frequent. Increased expression of Prx III was found to associate with the presence of progesterone (P = 0.02) and estrogen (P = 0.03) receptors, and Prxs IV (P = 0.009) and VI (P = 0.04) were overexpressed in progesterone receptor positive cases. Prx V was the only isoform that associated with items of tumor-node-metastasis classification, it was connected to a larger tumor size (P = 0.05) and positive lymph node status (P = 0.04). Prx V positivity was also connected with shorter survival (P = 0.04), whereas Prxs III (P = 0.002) and IV (P = 0.02) were related to better prognosis, probably resulting from their connection with a positive hormone receptor status. CONCLUSIONS: In conclusion, we found that expression of peroxiredoxins, especially III, IV and V, is increased in breast malignancy, suggesting the induction of Prxs as response to increased production of reactive oxygen species in carcinomatous tissue.     

Incidence of Helicobacter pylori strains activating neutrophils in patients with peptic ulcer disease.

A total of 61 human gastric isolates of Helicobacter pylori were studied for their ability to induce an oxidative burst in human neutrophils measured by luminol enhanced chemiluminescence. About one third of the strains induced strong and rapid chemiluminescence in neutrophils even without serum opsonins and agglutinated these cells on glass slides within two minutes. For other strains complement was required, although even then the reactions remained at a lower level. The activating and agglutinating property was bound to the cells, heat labile, and sensitive to several enzymes but resistant to acid. Strains possessing such activity were more common in patients with peptic ulcer disease than in patients with active chronic gastritis only (p = 0.0261, Fisher's exact test, two tailed). The activity shown might be a new indicator for ulcerogenic strains and could also partly explain the accumulation of neutrophils in the gastric mucosa during H pylori infection.     

Macro-optical trapping for sample confinement in light sheet microscopy

Light sheet microscopy is a powerful approach to construct three-dimensional images of large specimens with minimal photo-damage and photo-bleaching. To date, the specimens are usually mounted in agents such as agarose, potentially restricting the development of live samples, and also highly mobile specimens need to be anaesthetized before imaging. To overcome these problems, here we demonstrate an integrated light sheet microscope which solely uses optical forces to trap and hold the sample using a counter-propagating laser beam geometry. Specifically, tobacco plant cells and living Spirobranchus lamarcki larvae were successfully trapped and sectional images acquired. This novel approach has the potential to significantly expand the range of applications for light sheet imaging.OCIS codes: (110.0180) Microscopy, (110.0110) Imaging systems, (180.6900) Three-dimensional microscopy, (350.4855) Optical tweezers or optical manipulation     

Associations between polymorphisms of LSAMP gene and schizophrenia

The purpose of this study was to explore relationships between single-nucleotide polymorphisms (SNPs) in the limbic system-associated membrane protein (LSAMP) gene and schizophrenia. Twenty-two SNPs were analysed in 127 unrelated schizophrenic patients and in 171 healthy controls. The results showed significant allelic and haplotypic associations between LSAMP gene and schizophrenia.     

GLI1-induced mammary gland tumours are transplantable and maintain major molecular features

Increased expression of GLI1, the main Hedgehog signalling pathway effector, is related to unfavourable prognosis and progressive disease of certain breast cancer subtypes. We used conditional transgenic mice induced to overexpress GLI1 in the mammary epithelium either alone or in combination with deletion of one Trp53 allele to address the role of elevated GLI1 expression in breast tumour initiation and progression. Induced GLI1 expression facilitates mammary gland tumour formation and this was further increased upon heterozygous deletion of Trp53. The GLI1-induced primary tumours were of different murine molecular subtypes, including Normal-like^Ex, Class8^Ex, Claudin-Low^Ex and Erbb2-like^Ex. The gene expression profiles of some of the tumours correlated well with the PAM50 subtypes for human breast cancer. Whole-exome sequencing revealed somatic mutation profiles with only little overlap between the primary tumours. Orthotopically serially transplanted GLI1-induced tumours maintained the main morphological characteristics of the primary tumours for ≥10 generations. Independent of Trp53 status and molecular subtype, the serially transplanted GLI1-induced tumours were able to grow both in the absence of transgenic GLI1 expression and in the presence of the GLI1 inhibitor GANT61. These data suggest that elevated GLI1 expression has a determinant role in tumour initiation; however, additional genetic events are required for tumour progression.