Blood pressure changes following chronic administration to rats of 3beta,16beta-dihydroxy-5-androsten-17-one, 3beta,17beta-dihydroxy-5-androsten-16-one and 21-hydroxy-4-pregnene-3,20-dione-21-acetate.

The urinary excretion of 3beta,16beta-dihydroxy-5-androsten-17-one (16beta-OH-DHEA) is increased in patients with low renin essential hypertension. This steroid and its isomer 3beta,17beta-dihydroxy-5-androsten-16-one (16-oxo-A) have also been reported to have mineralocorticoid activity in adrenalectomized rats. These findings have led to the postulate that excessive secretion of 16beta-OH-DHEA may be responsible for the production of low renin essential hypertension. In this study unilaterally nephrectomized salt loaded rats injected once a week with 30 mg of 11-desoxycorticosterone acetate per/kg of body weight for 2 month periods developed hypertension. Rats given similar amounts of 16beta-OH-DHEA or 16-oxo-A and rats given no steroids did not develop hypertension. We conclude that it is unlikely that 16beta-OH-DHEA and 16-oxo-A are direct causative factors in the production of low renin essential hypertension.     

Untersuchungen über die Verteilung der ABO-Blutgruppen bei verschiedenen Erkrankungen im Säuglingsalter

Summary In the last ten years the ABO blood groups of our infants have been constantly ascertained and their distribution among some of the more prevalent diseases have been investigated. Other infants and healthy new-borns were used for comparison. The following results have been found:The blood group O is slightly more frequent in sick babies than in healthy new-borns. Among patients, who were under the age of 2 months at the time of admission, there were more with blood group O than among the older children. The blood group A tends to increase among the infants with anemia and with acute respiratory diseases, the blood group O tends to increase among those with staphylococcal infections and rachitis. With the latter the blood group B seems also to be found a little more frequently.Statistics show the increase of the blood group A in anemia in the 3. and 4. months of life and in acute respiratory diseases between the 3. and 12. month of life. The increase of the blood group O in staphylococcal infections is sure only among the youngest patients during their 1. month of life, it is obvious among the older patients, and there mainly among those of masculine sex. The increase of the blood groups O and B among infants with rachitis at the age of 3 to 12 months is almost certain. Premature babies show a sure decrease of the blood group O among both sexes, an increase of the blood group A among feminine, and of the blood group B among masculine patients.     

Computed tomography of the thorax in rabbits: a prospective study in ten clinically healthy New Zealand White rabbits

Background

Literature investigating the normal cross-sectional anatomy of rabbits with computed tomography (CT) is sparse and incomplete. The purpose of the present study was to investigate the normal thoracic structures, in particular the cranial thorax, with CT angiography in 10 clinically healthy New Zealand White (NZW) rabbits.

Results

Absolute and relative measurements of the trachea, heart, thoracic caudal vena cava and aorta, right and left principal bronchi, right and left caudal lobar bronchi and the accompanying branches of the right and left pulmonary artery and vein, right and left lung volume and lung density were taken. The three lobes of the thymus (right ventral, right dorsal and left thoracic lobes) were identified in all rabbits. Both the right dorsal and left thoracic lobes of the thymus extended between the heart and thoracic wall in all individuals with the left lobe reaching more caudally in seven animals. Consequently, the craniocaudal extension of the left lung was smaller than the right lung in these rabbits. Volume of the left lung was significantly smaller than the right (P = 0.005). The cranial mediastinal, right and left tracheobronchial and the aortic thoracic lymph nodes were very small and identified in four, four, seven and ten rabbits, respectively. The heart took up a median of 4.0 intercostal spaces, and in seven rabbits, it was located in the 2nd–5th intercostal space. Median relative cardiac height and width measured 74 and 88%, respectively. The median angle of the trachea to the spine was 5°. Median density between the right and left lung did not significantly differ (? 549 and ? 583 Hounsfield units, respectively). In all but one rabbit, atelectasis was present and classified as mild, moderate or severe in six, two and one individuals, respectively. Mild subclinical bronchopneumonia was diagnosed in seven rabbits.

Conclusions

The present study provides species-specific anatomical CT information and reference values for structures in the thorax of the NZW rabbit. Subclinical bronchopneumonia appears to be a common CT finding.

     

Nuclear localization of the Arabidopsis blue light receptor cryptochrome 2

The cryptochrome blue light photoreceptor family of Arabidopsis thaliana consists of two members, CRY1 and CRY2 (PHH1). CRY2 contains a putative nuclear localization signal (NLS) within its C-terminal region. We examined whether CRY2 is localized in the nucleus and whether the C-terminal region of CRY2 is involved in nuclear targeting. Total cellular and nuclear protein extracts from Arabidopsis were subjected to immunoblot analysis with CRY2-specific antibodies. Strong CRY2 signals were obtained in the nuclear fraction. Fusion proteins consisting of the green fluorescent protein (GFP) and different fragments of CRY2 were expressed in parsley protoplasts and the localization of the fusion proteins was determined by fluorescence and confocal laser scanning microscopy. GFP-fusions containing the entire CRY2 protein or its C-terminal region were found exclusively in the nucleus. We conclude from these results that CRY2 is localized in the nucleus and that nuclear localization is mediated by the C-terminal region of CRY2.     

Removal of deaminated cytosines and detection of in vivo methylation in ancient DNA

DNA sequences determined from ancient organisms have high error rates, primarily due to uracil bases created by cytosine deamination. We use synthetic oligonucleotides, as well as DNA extracted from mammoth and Neandertal remains, to show that treatment with uracil–DNA–glycosylase and endonuclease VIII removes uracil residues from ancient DNA and repairs most of the resulting abasic sites, leaving undamaged parts of the DNA fragments intact. Neandertal DNA sequences determined with this protocol have greatly increased accuracy. In addition, our results demonstrate that Neandertal DNA retains in vivo patterns of CpG methylation, potentially allowing future studies of gene inactivation and imprinting in ancient organisms.     

Cognitive behavioural therapy versus supportive therapy for persistent positive symptoms in psychotic disorders: The POSITIVE Study, a multicenter, prospective, single-blind, randomised controlled clinical trial

Background

It has been demonstrated that cognitive behavioural therapy (CBT) has a moderate effect on symptom reduction and on general well being of patients suffering from psychosis. However, questions regarding the specific efficacy of CBT, the treatment safety, the cost-effectiveness, and the moderators and mediators of treatment effects are still a major issue. The major objective of this trial is to investigate whether CBT is specifically efficacious in reducing positive symptoms when compared with non-specific supportive therapy (ST) which does not implement CBT-techniques but provides comparable therapeutic attention.

Methods/Design

The POSITIVE study is a multicenter, prospective, single-blind, parallel group, randomised clinical trial, comparing CBT and ST with respect to the efficacy in reducing positive symptoms in psychotic disorders. CBT as well as ST consist of 20 sessions altogether, 165 participants receiving CBT and 165 participants receiving ST. Major methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, analysis by intention to treat, data management using remote data entry, measures of quality assurance (e.g. on-site monitoring with source data verification, regular query process), advanced statistical analysis, manualized treatment, checks of adherence and competence of therapists. Research relating the psychotherapy process with outcome, neurobiological research addressing basic questions of delusion formation using fMRI and neuropsychological assessment and treatment research investigating adaptations of CBT for adolescents is combined in this network. Problems of transfer into routine clinical care will be identified and addressed by a project focusing on cost efficiency.

Discussion

This clinical trial is part of efforts to intensify psychotherapy research in the field of psychosis in Germany, to contribute to the international discussion on psychotherapy in psychotic disorders, and to help implement psychotherapy in routine care. Furthermore, the study will allow drawing conclusions about the mediators of treatment effects of CBT of psychotic disorders.

Trial Registration

Current Controlled Trials ISRCTN29242879     

Murine B16 melanomas expressing high levels of the chemokine stromal-derived factor-1/CXCL12 induce tumor-specific T cell chemorepulsion and escape from immune control

The chemokine, stromal-derived factor-1/CXCL12, is expressed by normal and neoplastic tissues and is involved in tumor growth, metastasis, and modulation of tumor immunity. T cell-mediated tumor immunity depends on the migration and colocalization of CTL with tumor cells, a process regulated by chemokines and adhesion molecules. It has been demonstrated that T cells are repelled by high concentrations of the chemokine CXCL12 via a concentration-dependent and CXCR4 receptor-mediated mechanism, termed chemorepulsion or fugetaxis. We proposed that repulsion of tumor Ag-specific T cells from a tumor expressing high levels of CXCL12 allows the tumor to evade immune control. Murine B16/OVA melanoma cells (H2b) were engineered to constitutively express CXCL12. Immunization of C57BL/6 mice with B16/OVA cells lead to destruction of B16/OVA tumors expressing no or low levels of CXCL12 but not tumors expressing high levels of the chemokine. Early recruitment of adoptively transferred OVA-specific CTL into B16/OVA tumors expressing high levels of CXCL12 was significantly reduced in comparison to B16/OVA tumors, and this reduction was reversed when tumor-specific CTLs were pretreated with the specific CXCR4 antagonist, AMD3100. Memory OVA-specific CD8+ T cells demonstrated antitumor activity against B16/OVA tumors but not B16/OVA.CXCL12-high tumors. Expression of high levels of CXCL12 by B16/OVA cells significantly reduced CTL colocalization with and killing of target cells in vitro in a CXCR4-dependent manner. The repulsion of tumor Ag-specific T cells away from melanomas expressing CXCL12 confirms the chemorepellent activity of high concentrations of CXCL12 and may represent a novel mechanism by which certain tumors evade the immune system.     

Synergistic and additive antiproliferative effects on human leukemia cell lines induced by combining acetylenehexacarbonyldicobalt complexes with the tyrosine kinase inhibitor imatinib

The tyrosine kinase inhibitor imatinib is successfully used in the treatment of chronic myeloid leukemia, but the occurrence of resistance phenomena can significantly limit therapeutic impact. Imatinib shows synergistic effects with cisplatin, suggesting that the coadministration of different cytostatics might reestablish the efficacy of treatment. We recently demonstrated that cobalt alkyne (or acetylenehexacarbonyldicobalt) complexes induce antiproliferative activity in human leukemia and lymphoma cells. The present study evaluates the effects of cobalt alkyne compounds containing propargylic acid esters on human acute (HL-60) and chronic myeloid (LAMA-84 and CML-T1) leukemia cell lines. The cell growth inhibitory activities (IC(50) values of 9.5 microM and higher) and induction of apoptosis (maximum 5.5-fold increase of single-stranded DNA at a drug concentration of 50 microM) achieved with the single agents were moderate. Interestingly, suboptimal concentrations of the cobalt complexes (10 microM) together with imatinib (0.1 microM), when coadministered, showed an additive or synergistic effect on cellular proliferation inhibition. The most promising results were obtained with complexes containing ligands derived from the nonsteroidal antiinflammatory drugs acetylsalicylic acid and naproxene.