First international intercomparison of luminescence techniques using samples from the Techa River Valley.

Bricks collected from a contaminated village (Muslyumovo) of the lower Techa river valley, Southern Urals, Russia, were measured using thermoluminescence and optically stimulated luminescence by four European laboratories and a U.S. laboratory to establish and compare the applied dose reconstruction methodologies. The bricks, collected from 60-100-year-old buildings, had accumulated a relatively high dose due to natural sources of radiation in the brick and from the surrounding environment. This work represents the results of a first international intercomparison of luminescence measurements for bricks from the Southern Urals. The luminescence measurements of absorbed dose in bricks collected from the most shielded locations of the same buildings were used to determine the background dose due to natural sources of radiation and to validate the age of the bricks. The absorbed dose in different bricks measured by four laboratories using thermoluminescence and optically stimulated luminescence at a depth of 10 +/- 2.5 mm from the exposed brick surface agreed within +/-21%. After subtraction of the natural background dose, the absorbed dose in brick due to contaminated river sediments and banks was calculated and found to range between 150 and 200 mGy. The cumulative doses in brick due to man-made sources of radiation at 100 and 130 mm depths in the bricks were also measured and found to be consistent with depth dose profiles calculated by Monte Carlo simulations of photon transport for possible source distributions.     

Neutralization assay using a modified vaccinia virus Ankara vector expressing the green fluorescent protein is a high-throughput method to monitor the humoral immune response against vaccinia virus

Vaccination against smallpox is again considered in order to face a possible bioterrorist threat, but the nature and the level of the immune response needed to protect a person from smallpox after vaccination are not totally understood. Therefore, simple, rapid, and accurate assays to evaluate the immune response to vaccinia virus need to be developed. Neutralization assays are usually considered good predictors of vaccine efficacy and more informative with regard to protection than binding assays. Currently, the presence of neutralizing antibodies to vaccinia virus is measured using a plaque reduction neutralization test, but this method is time-consuming and labor-intensive and has a subjective readout. Here, we describe an innovative neutralization assay based on a modified vaccinia virus Ankara (MVA) vector expressing the green fluorescent protein (MVA-gfp). This MVA-gfp neutralization assay is rapid and sensitive and has a high-throughput potential. Thus, it is suitable to monitor the immune response and eventually the efficacy of a large campaign of vaccination against smallpox and to study the vector-specific immune response in clinical trials that use genetically engineered vaccinia viruses. Most importantly, application of the highly attenuated MVA eliminates the safety concern in using the replication-competent vaccinia virus in the standard clinical laboratory.     

Association of hormone replacement therapy with bronchial hyper-responsiveness

Postmenopausal hormone replacement therapy (HRT) has been linked to asthma in women, however, with inconsistent conclusions. This study examined the association of HRT with bronchial hyper-responsiveness (BHR). Eighty-five postmenopausal women completed a women-specific questionnaire and underwent methacholine challenge testing according to the protocol of the European community respiratory health survey. Associations of HRT use with BHR (based on a 20% fall in FEV1), mild BHR (10% fall in FEV1) or dichotomized dose-response slopes were analyzed by logistic regression, controlling for age, education, smoking and overweight. The 27 HRT users were less likely to show BHR compared to the 58 non-users (11% vs. 41%), multiply adjusted odds ratio (95% confidence interval) 0.12 (0.03, 0.55). Results for dose-response slopes were similar, while mild BHR showed no association with HRT use. These results point to a relaxing effect of estrogens on bronchial smooth muscle.     

Prevalence and determinants of hormone replacement therapy in German women 1984-1995

OBJECTIVES: To describe trends in prevalence and determinants of hormone replacement therapy (HRT) in German women. METHODS: Three representative samples of women in Augsburg, Germany were examined in the MONICA surveys in 1984/85 (45-64 years; N=1013), 1989/90 and 1994/95 (both 45-74 years; N=1496 and 1475) by interview and anthropometry, and all drugs taken during the previous week were documented. The prevalence of HRT use was calculated by survey, age group and HRT type, and various characteristics were evaluated as determinants for any systemic HRT use by logistic regression. RESULTS: The prevalence of HRT use in women aged 45-64 years in 1984/85, 1989/90 and 1994/95 was 3, 9% (age 45-74, 6%) and 23% (17%), respectively. In 1994/1995, positive determinants of HRT use were daily consumption of salad and vegetables, having quit smoking (vs. current smoking), regular exercise, ever having taken oral contraceptives, body mass index <25 kg/m(2) and age, and negative determinants were not drinking alcohol and education for <9 years (all P-value <0.10 in multivariate model). After multiple adjustment, HRT users were five times more likely to have participated in cancer screening and to have visited a gynaecologist >or=5 times during the previous year, and were less likely not to have seen a general practitioner or gynaecologist (all P-values <0.001). CONCLUSION: HRT use increased substantially in Germany between 1984 and 1995. Women with characteristics associated with lower morbidity and mortality were more likely to use HRT, which agrees with the healthy-user phenomenon described in other countries.     

No evidence of association of FLJ10986 and ITPR2 with ALS in a large German cohort

A recent genome-wide association study (GWAS) found significant association of six single nucleotide polymorphisms (SNPs) in the gene FLJ10986 with sporadic amyotrophic lateral sclerosis (SALS). Another independent GWAS reported significant association of one SNP in the gene inositol 1,4,5-triphosphate receptor 2 (ITPR2) with SALS. These studies provided conflicting results. We examined the six most significant SNPs in FLJ10986 and one SNP in ITPR2 in a large cohort consisting of 595 SALS cases and 681 controls ascertained from Germany. Our results did not provide evidence for the association of these SNPs with SALS, suggesting a possible population-specific effect for FLJ10986 and ITPR2 that do not modulate the risk for SALS in the German population.     

Monocyte chemoattractant chemokines in cystic fibrosis

BackgroundNeutrophilic inflammation causes lung damage in cystic fibrosis (CF). Recent data from animal models suggest that the migration of blood monocytes into the airway supports neutrophil-mediated tissue injury. CF may therefore be associated with increased airway levels of chemoattractants for pro-inflammatory monocytes. In this study, we sought to assess the levels of monocyte chemoattractants CCL2 and CX3CL1 in the blood and airways of patients with CF, and expression of their respective receptors CCR2 and CX3CR1 on blood monocytes.MethodsBlood was obtained from 32 CF patients and 25 healthy controls. Induced sputum was obtained from a further 24 CF patients and 17 healthy controls. Expression of CCR2 and CX3CR1 on CD14++CD16− and CD14+CD16+ blood monocytes was determined by flow cytometry. CCL2 and CX3CL1 levels in blood and induced sputum were determined by ELISA.ResultsTotal blood monocyte concentration was not different between CF and controls. CCR2 was absent, and CX3CR1 higher on CD14+CD16+ monocytes from both CF and controls when compared with expression on CD14++CD16− cells. There was no difference in expression of chemokine receptors by either monocyte subpopulation between CF and controls. Blood CCL2, but not CX3CL1, was increased in CF patients (p = 0.006). Similarly, CF was associated with increased induced sputum CCL2, but not CX3CL1 (190.6 vs. 77.3pg/mL; p = 0.029).ConclusionCCL2, but not CX3CL1 is increased in the airway and blood of CF patients. Blood monocytes from CF patients are phenotypically competent to respond to CCL2, since they express normal levels of CCR2.     

Embryonic stem cells produce neurotrophins in response to cerebral tissue extract: Cell line-dependent differences

In the present study, we compare the capacity of two different embryonic stem (ES) cell lines to secrete neurotrophins in response to cerebral tissue extract derived from healthy or injured rat brains. The intrinsic capacity of the embryonic cell lines BAC7 (feeder cell-dependent cultivation) to release brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3) exceeded the release of these factors by CGR8 cells (feeder cell-free growth) by factors of 10 and 4, respectively. Nerve growth factor (NGF) was secreted only by BAC7 cells. Conditioning of cell lines with cerebral tissue extract derived from healthy or fluid percussion-injured rat brains resulted in a significant time-dependent increase in BDNF release in both cell lines. The increase in BDNF release by BAC7 cells was more pronounced when cells were incubated with brain extract derived from injured brain. However, differences in neurotrophin release associated with the origin of brain extract were at no time statistically significant. Neutrophin-3 and NGF release was inhibited when cell lines were exposed to cerebral tissue extract. The magnitude of the response to cerebral tissue extract was dependent on the intrinsic capacity of the cell lines to release neurotrophins. Our results clearly demonstrate significant variations in the intrinsic capability of different stem cell lines to produce neurotrophic factors. Furthermore, a significant modulation of neurotrophic factor release was observed following conditioning of cell lines with tissue extract derived from rat brains. A significant modulation of neurotrophin release dependent on the source of cerebral tissue extract used was not observed.     

Sense of coherence,health locus of control,and quality of life in obese adults: physical limitations and psychological normalcies

OBJECTIVES: To assess differences between overweight and normal-weight adults in sense of coherence (SOC), health locus of control (HLOC), and health-related quality of life (HQOL). METHODS: Cross-sectional population study (Augsburg, Germany). Random sample aged 25-74 (N=947). Body mass index (BMI) was categorized into four groups (normal-weight: 18.5-25; pre-obesity: 25-29.9; moderate obesity: 30-34.9; severe obesity: > or =35). The associations between obesity classification and SOC-13T, MHLOC-Scales, and SF-12 summary scores were estimated via analysis of covariance. RESULTS: Adjusted for age and socio-economic status, no differences across BMI-groups related to SOC, internal HLOC, external HLOC-'chance', and SF-12-'mental health'. HLOC-'doctors' was marginally elevated in obese women. Larger differences pertained to SF-12-'physical health' in that it was considerably reduced in obese women and severely obese men. CONCLUSIONS: In this adult population sample, obesity is not associated with SOC, HLOC, and HQOL in terms of mental health, but is associated with poorer physical health, which was reported by all groups of obese women, and by severely obese men. These results underline the need to treat and prevent obesity to restore and promote physical HQOL, and to distinguish moderate vs. severe obesity in obesity research.     

mNotch1 signaling reduces proliferation of myeloid progenitor cells by altering cell-cycle kinetics

Notch receptors are involved in the regulation of cell-fate decisions, differentiation, and proliferation in many tissues. The expression of Notch receptors on hemopoietic cells and of cognate ligands on bone marrow stromal cells suggests a possible role for Notch signaling in the regulation of hemopoiesis. We were interested to assess the involvement of Notch1 signaling on cell proliferation of myeloid progenitor cells. Proliferation, cell-cycle status, and apoptosis of myeloid progenitor 32D cell lines engineered to permit the conditional induction of the constitutively active intracellular domain of mNotch1 (mN1(IC)) by the 4-hydroxytamoxifen(OHT)-inducible system were analyzed in the presence or absence of OHT.The induction of mN1(IC) by OHT resulted in reduction of proliferation (p<0.01) and accumulation of cells in the G(1)/G(0) phase of the cell cycle (p<0.001) without substantially affecting apoptosis of 32D cells. These effects were observed under culture conditions that allow differentiation and, to a lesser degree, under conditions that normally promote self-renewal in the absence of differentiated cells. Our data suggest that mNotch1 signaling suppresses proliferation of myeloid progenitor cells by altering cell-cycle kinetics.