Use of real-time, label-free analysis in revealing low-affinity binding to blood group antigens by Helicobacter pylori.

Infectious diseases are often initiated by microbial adherence that is mediated by the binding of attachment molecules, termed adhesins, to cell surface receptors on host cells. We present an experimental system, oblique-incidence reflectivity difference (OI-RD) microscopy, which allows the detection of novel, low-affinity microbial attachment mechanisms that may be essential for infectious processes. OI-RD microscopy was used to analyze direct binding of the oncopathogen, Helicobacter pylori ( H. pylori ) to immobilized glycoconjugates in real time with no need for labeling tags. The results suggest the presence of additional Lewis b blood group antigen (Le(b)) binding adhesins that have not been detected previously. OI-RD microscopy also confirmed the high-affinity binding of H. pylori outer-membrane protein BabA to Le(b). The OI-RD microscopy method is broadly applicable to real-time characterization of intact microbial binding to host receptors and offers new strategies to elucidate the molecular interactions of infectious agents with human host cells.

Uptake and bioaccumulation of PCDD/Fs in earthworms after in situ and in vitro exposure to soil from a contaminated sawmill site.

Uptake of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) was studied in earthworms collected from a sawmill site in Sweden with severe PCDD/Fs contamination (the hot spot concentration was 690,000ng TEQWHO2005/kg d.w.) in order to investigate the transfer of PCDD/Fs from the site to the biota. PCDD/Fs concentrations in the collected earthworms were compared to PCDD/Fs concentrations in laboratory exposed earthworms (Eisenia fetida), which were exposed to contaminated soils from the sawmill site for 34days. All analyses were performed by high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS). PCDD/Fs concentrations in the earthworms ranged from 290 to 520,000pg/g (f.w.). The main congeners found in both soils and earthworms were OCDF, 1234678-HpCDF, OCDD and 1234678-HpCDD. The study showed that the PCDD/Fs in the soil were biovailable to the earthworms and the PCDD/Fs concentrations in the soils correlated with the concentrations in the earthworms. Earthworm samples from soil with lower concentration had higher bioaccumulation factors than samples from soils with high concentration of contamination. Thus, a less contaminated soil could yield higher concentrations in earthworms compared to a higher contaminated soil. Assuming that when assessing risks with PCDD/F contaminated soil, a combination of chemical analysis of soil PCDD/Fs concentrations and bioavailability should be employed for a more comprehensive risk assessment.

Infrequent use of antidepressants in depressed individuals (an interview and prescription database study in a defined Swedish population 2001-2002).

PURPOSE: To investigate whether antidepressants are over-used, under-used, or misused, by determining to what extent the depressed individuals in a defined population are treated with antidepressant medication and, from the other end, to what extent prescribed antidepressants are aimed for the treatment of depression. SUBJECTS AND METHOD: From an individual based prescription database in the County of Jämtland, 2048 individuals representative for the general population were selected. The presence of current depression in these individuals was screened by a mailed self-screening questionnaire. Individuals with depression according to the questionnaire were interviewed by a psychiatrist using a structured interview (SCAN) to confirm the diagnosis. Their use of antidepressants was obtained from the prescription database. RESULTS: Sixty-two (4.5%) out of 1375 were diagnosed with depression and 17 (27%) of these were taking an antidepressant. In addition 44 individuals, currently not depressed, were taking antidepressants. Twenty-five of these were interviewed per telephone and it was found that the indications for 18 of them were continuation treatment of depression, and for seven of them pain, sleep disturbance or anxiety. CONCLUSION: Antidepressants appear to be under-used in the population. Only one in four of the depressed individuals was treated with antidepressant medication. Those who had antidepressant medication without being currently depressed had, with few exceptions, either continuation treatment for depression in remission or treatment on other approved indications.

Overexpression of the scaffold WD40 protein WRAP53ß enhances the repair of and cell survival from DNA double-strand breaks.

Altered expression of the multifunctional protein WRAP53ß (WD40 encoding RNA Antisense to p53), which targets repair factors to DNA double-strand breaks and factors involved in telomere elongation to Cajal bodies, is linked to carcinogenesis. While loss of WRAP53ß function has been shown to disrupt processes regulated by this protein, the consequences of its overexpression remain unclear. Here we demonstrate that overexpression of WRAP53ß disrupts the formation of and impairs the localization of coilin to Cajal bodies. At the same time, the function of this protein in the repair of DNA double-strand breaks is enhanced. Following irradiation, cells overexpressing WRAP53ß exhibit more rapid clearance of phospho-histone H2AX (γH2AX), and more efficient homologous recombination and non-homologous end-joining, in association with fewer DNA breaks. Moreover, in these cells the ubiquitylation of damaged chromatin, which is known to facilitate the recruitment of repair factors and subsequent repair, is elevated. Knockdown of the ubiquitin ligase involved, ring-finger protein 8 (RNF8), which is recruited to DNA breaks by WRAP53ß, attenuated this effect, suggesting that overexpression of WRAP53ß leads to more rapid repair, as well as improved cell survival, by enhancing RNF8-mediated ubiquitylation at DNA breaks. Our present findings indicate that WRAP53ß and RNF8 are rate-limiting factors in the repair of DNA double-strand breaks and raise the possibility that upregulation of WRAP53ß may contribute to genomic stability in and survival of cancer cells.

Selective serotonin reuptake inhibitors have broadened the utilisation of antidepressant treatment in accordance with recommendations. Findings from a Swedish prescription database.

BACKGROUND: With the advent of the selective serotonin reuptake inhibitors (SSRIs), the use of antidepressants has increased drastically in Sweden. The use of tricyclic antidepressants (TCAs) has, however, decreased. METHODS: We surveyed a prescription database in the Swedish county of Jämtland and compared prescription patterns for patients prescribed SSRIs with those prescribed TCAs. RESULTS: The incidence of treatments of antidepressants increased from 0.76% to 1.33% during the period 1991-1996. There were no significant differences between SSRIs and TCAs with regard to patients having only one prescription dispensed within three months from the index prescription, or patients who switched class of antidepressant. Only a minority of the treatments were continued for at least six months, but significantly more SSRI than TCA treatments (42% and 27%). A second treatment period suggesting recurrence was three-times more common in the TCA group than in the SSRI group. CONCLUSION: Provided that the increased use of SSRIs is mainly for depression, these drugs appear, despite a lower efficacy in severe depression, to have enabled a broader utilisation of antidepressants with regard to incidence, dosage and duration, in accordance with recommendations. Further analyses of this phenomenon relative to diagnostic criteria and outcome measures are required.

Assessment of PCDD/Fs levels in soil at a contaminated sawmill site in Sweden--a GIS and PCA approach to interpret the contamination pattern and distribution.

Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) were analysed in soil from a Swedish sawmill site where chlorophenols (CPs) had been used more than 40 years ago. The most contaminated area at the site was the preservation subarea where the PCDD/F WHO2005-TEQ level was 3450 times higher than the current Swedish guideline value of 200 ng TEQ/kg soil for land for industrial use. It was also shown that a fire which destroyed the sawmill might have affected the congener distribution at the concerned areas. To get a broader picture of the contamination both GIS (spatial interpolation analysis) and multivariate data analysis (PCA) were applied to visualize and compare PCDD/F levels as well as congener distributions at different areas at the site. It is shown that GIS and PCA are powerful tools in decisions on future investigations, risk assessments and remediation of contaminated sites.

WRAP53 promotes cancer cell survival and is a potential target for cancer therapy.

We previously identified WRAP53 as an antisense transcript that regulates the p53 tumor suppressor. The WRAP53 gene also encodes a protein essential for Cajal body formation and involved in cellular trafficking of the survival of motor neuron complex, the telomerase enzyme and small Cajal body-specific RNAs to Cajal bodies. Here, we show that the WRAP53 protein is overexpressed in a variety of cancer cell lines of different origin and that WRAP53 overexpression promotes cellular transformation. Knockdown of the WRAP53 protein triggers massive apoptosis through the mitochondrial pathway, as demonstrated by Bax/Bak activation, loss of mitochondrial membrane potential and cytochrome c release. The apoptosis induced by WRAP53 knockdown could moreover be blocked by Bcl-2 overexpression. Interestingly, human tumor cells are more sensitive to WRAP53 depletion as compared with normal human cells indicating that cancer cells in particular depends on WRAP53 expression for their survival. In agreement with this, we found that high levels of WRAP53 correlate with poor prognosis of head and neck cancer. Together these observations propose a role of WRAP53 in carcinogenesis and identify WRAP53 as a novel molecular target for a large fraction of malignancies.

Increased antidepressant use and fewer suicides in Jämtland county, Sweden, after a primary care educational programme on the treatment of depression.

OBJECTIVE: To consider and evaluate a continuing medical education programme for general practitioners (GPs) on depression in Jämtland county, Sweden, inspired by the Gotland study. METHOD: Interactive seminars were conducted between 1995 and 2002 in Jämtland county. For evaluation, suicide rates and annual sales statistics of antidepressants were compared with national averages. Questionnaires were used for information about attitudes and prescribing habits. RESULTS: The suicide rate in Jämtland decreased to the same level as the national average. The use of antidepressants increased from 25% below the Swedish average to the same level. The selective serotonin re-uptake inhibitors (SSRIs) were preferred because of their tolerability. Suicide issues were considered to be most important in the management of depressed patients. CONCLUSION: A trend towards a greater prescription of antidepressants and fewer suicides after an educational programme on depression for GPs replicated the findings from the Gotland study. The educational programme will be conducted annually and could be a model for other regions.

[Dynamic short-term psychotherapy--current aspects]. / Dynamisk korttidspsykoterapi--aktuella aspekter.

Short-term dynamic psychotherapy is a brief form of conflict-oriented psychotherapy based upon psychoanalytical theory. Apart from the time aspect and the therapist's active approach, the therapeutic framework is similar to that of long-term insight-oriented psychotherapy. The emphasis is placed upon patient-therapist interaction in the therapeutic process.

Suicides are seldom prescribed antidepressants: findings from a prospective prescription database in Jämtland county, Sweden, 1985-95.

OBJECTIVE: This study presents data relating to prospectively monitored treatment and post-mortem toxicology of individuals who committed suicide. METHOD: A case-control study of prospectively monitored pharmacological treatment in suicides and controls. Psychiatric records and post-mortem toxicology were also studied. RESULTS: Fifty-nine subjects who committed suicide purchased twice the number of prescriptions as the 118 controls. Sixteen cases received psychiatric in-patient care compared to four of the controls. In the last 3 months prior to suicide, 38 cases (64%) were dispensed drugs: anxiolytics-hypnotics in 17 cases (29%), antipsychotics in six cases (10%) and antidepressants in seven cases (12%). More psychiatrists than GPs prescribed antidepressants. About one-third of psychotropic drugs were retrieved in post-mortem toxicology. CONCLUSION: There is a frequent use of psychotropics and psychiatric care among suicides; however, few used antidepressants and complied. Many suicides are still misdiagnosed and are not adequately treated.

Indications for and outcome of antidepressant medication in a general population: a prescription database and medical record study, in Jämtland county, Sweden, 1995.

OBJECTIVE: To examine the indications for prescribing antidepressants and the clinical outcome when they are prescribed for the treatment of depression, and compare tricyclic antidepressants (TCAs) and selective serotonin re-uptake inhibitors (SSRIs) in these respects. METHOD: A naturalistic study of a prospective prescription monitoring database and medical records. RESULTS: Depression was the indication for 23% of the tricyclic treatments and for 82% of the SSRI treatments. A successful treatment of the depression was found in 20% of the TCA cases and 41% of the SSRI cases (NS). CONCLUSION: This study provides evidence that the main use of SSRIs in 1995 is the treatment of depression. The study implies that SSRIs have a more favourable outcome in "real life" than TCAs.

Nocturia and depression.

OBJECTIVE: To assess the possible relationship between major depression (MD) and nocturia. SUBJECTS AND METHODS: An unselected group of adult men and women, living in the city of Ostersund, Sweden, were sent a postal questionnaire containing questions on somatic and mental health, sleep, sleepiness and nocturia. For depression diagnostics the Major Depression Inventory (MDI) was used. RESULTS: The mean (sd) ages of the men and women were 48.0 (18.2) and 50.1 (19.1) years, respectively. Two or more nocturnal micturition episodes occurred in 15.6% of the men and 16.5% of the women. In a multiple logistic regression analysis independent correlates (with 95% confidence intervals) for >/= 2 nocturnal voids in men were: MD 6.5 (2.6-15.6); health, fair vs good, 1.8 (1.0-3.9); health, poor vs good, 2.7 (1.1-4.8); age, 60-74 vs 18-29, 3.6 (1.5-8.4) and age >/= 75 vs 18-29 6.7 (2.6-17.4); and in women: MD 2.8 (1.3-6.3); health, fair vs good, 1.9 (1.1-3.2); health, poor vs good, 4.3 (2.6-8.2); age, 60-74 vs 18-29, 3.8 (1.8-7.8), and age >/= 75 vs 18-29, 8.6 (4.0-18.6). Age < 60 years was deleted by the logistic model in both sexes. CONCLUSION: MD is associated with a six-fold increase in nocturia in men and a three-fold increase in women, after accounting for age and health. Possible pathogenetic mechanisms of this relationship may involve both increased nocturnal diuresis via a disturbed 24-h rhythm of antidiuretic hormone secretion, and a decrease in nocturnal bladder capacity through a central and/or peripheral serotonergic effect.