Subinhibitory concentrations of antibiotics induce phenazine production in a marine Streptomyces sp

Subinhibitory concentrations of antibiotics were found to enhance and modulate the production of new phenazines, streptophenazines A-H, in a marine Streptomyces isolate. The streptophenazines differ in length and substitution of an alkyl chain. The pattern of metabolites formed depends on the antibiotic used. In the presence of tetracycline, streptophenazines F and G were induced and the production of streptophenazines A-D was increased. When using bacitracin, mainly streptophenazine H was produced. Streptophenazines C and H showed moderate activity against Bacillus subtilis, while streptophenazine C was also active against Staphylococcus lentus.     

The MPO Study: just a European HEMO Study or something very different?

Although results from observational and epidemiological studies suggested a survival benefit associated with high-flux hemodialysis, conclusive evidence from prospective randomized clinical trials has been lacking. Both the HEMO Study in the USA and the Membrane Permeability Outcome Study (MPO Study) in Europe are randomized studies investigating the effect of high- and low-flux hemodialysis on patient outcomes, even though there were some significant differences in the design of the two studies. An earlier randomized clinical trial could not show differences on patient survival between patient groups being treated with membranes of different material and permeability, but this trial was not designed specifically to examine this particular endpoint. Based on these previous experiences, the MPO Study addressed a hemodialysis patient population which was considered to be more susceptible to the intervention with high-flux dialysis. To identify these patients with an elevated risk, low serum albumin levels were chosen as an indicator; low serum albumin is associated with malnutrition, inflammation, atherosclerosis, and with increased risk of morbidity and mortality. Together with low serum albumin, patients had to be new to dialysis to be selected for the MPO Study. These particular considerations on patient selection, together with additional methodological refinements in the study design allow the conclusion that the MPO Study is valid on its own rather than being a European version of the HEMO Study.     

Both chromosome 13 abnormalities by metaphase cytogenetics and deletion of 13q by interphase FISH only are prognostically relevant in multiple myeloma

OBJECTIVES: Deletion of chromosome 13q [del(13q)] has emerged as a major adverse prognostic factor in multiple myeloma (MM). Del(13q) is detected two to three times more frequently by interphase fluorescence in situ hybridization (FISH) than by metaphase cytogenetics (CG). However, it has remained unclear whether or not del(13q) detected by FISH only provides the same prognostic information as its detection by CG. METHODS: We investigated the outcome of 118 consecutive patients with newly diagnosed MM who were studied by both CG and FISH (RB-1 and/or D13S319 probes). RESULTS: CG revealed informative MM karyotypes in 35 patients (29.7%), with monosomy 13/del(13q) in 16 of them. FISH was indicative for a del(13q) in 43 patients (36.4%). A del(13q) by FISH was present in all 16 patients with monosomy 13/del(13q) by CG and also in four of 19 patients with informative karyotypes and diploid chromosome 13. Furthermore, del(13q) was present by FISH in 23 of 84 patients with diploid/non-informative metaphases by CG. Overall survival of patients with monosomy 13/del(13q) by CG and of patients with del(13q) by FISH only was not significantly different (median, 35.2 months vs. 33.2 months, P = 0.58). In contrast, patients with diploid chromosome 13 by either technique experienced prolonged survival (median, 65.6 months). Presence of abnormal karyotypes was significantly associated with an increased Ki67 growth fraction. CONCLUSION: FISH of chromosome 13q adds prognostic information to that provided by CG. It is suggested to use FISH analysis in clinical trials if risk stratifications take into consideration the chromosome 13q status.     

Functional significance of prorenin internalization in the rat heart

Intracardiac renin is considered to be involved in the pathogenesis of cardiac hypertrophy, fibrosis, and myocardial infarction. Cardiac renin is predominantly derived from the circulation, because preprorenin is not expressed locally and uptake of renin has been demonstrated. One mechanism of internalization recently described involves the mannose-6-phosphate receptor and requires glycosylation of renin. Based on previous observations, we considered the existence of another pathway of uptake, not requiring glycosylation and predominantly involving prorenin. This hypothesis and its functional consequences were investigated in vitro and in vivo. We demonstrate that isolated adult cardiomyocytes internalize unglycosylated prorenin, which is followed by the generation of angiotensins. We further show that transgenic rats, expressing the ren-2(d) renin gene in an inducible manner, exhibit markedly enhanced levels of unglycosylated renin within intracellular compartments in the heart as a consequence of the induction of hepatic transgene expression and the rise of circulating unglycosylated prorenin levels. Because in this model severe cardiac damage occurs as a consequence of the rise of circulating prorenin levels, internalization of prorenin into cardiac cells is likely to play a key role in this process.     

Remoteness and Valence of Autobiographical Memory in Depression

We examined whether major depressive disorder (MDD) is associated with a tendency to recall more remote, specific autobiographical memories, particularly in the context of positive memories. To this end, individuals with MDD (n?=?26) and healthy controls (n?=?54) completed the Autobiographical Memory Test. Consistent with the hypothesis, remoteness of specific memories in the MDD group, but not the control group, depended on valence. Compared to the control group, the MDD group recalled more remote positive events. Additionally, the MDD group’s positive specific memories were significantly more remote than their negative specific memories. Retrieving remote positive memories might impair mood regulation and maintain an individual’s negative mood and perpetuate depression.     

Tracking the Phylogeny of Seagrasses: Inferred from 18S rRNA Gene and Ancestral State Reconstruction of Morphological Data

Taxonomic challenges of seagrasses were met by using 18S ribosomal subunit of ribosomal deoxyribonucleic acid (18S rDNA) sequence data of 14 seagrass species from India and two temperate species from Germany. The phylogenetic trees presented are based on the 18S rDNA sequence analysis of 41 nucleotide sequences including sequences obtained in the present study as well as previously published sequences of freshwater and saltmarsh plants, and seagrasses for identifying the evolutionary lineage. The 18S rDNA data indicates independent origin of temperate and tropical seagrasses with the genus Halophila as the intermediate group for both the regions. Based on the complex morphological structures the Halophila group represents the basal form among seagrasses whereas Enhalus is considered to be the most recently originated seagrass species. In that context, the marine Hydrocharitaceae group of Enhalus, Thalassia and Halophila has been proposed to be separated into two groups such as Enhalus/Thalassia and Halophila subfamilies. Hence, the present systematic studies warrant a revised taxonomy for seagrasses, which better reflects the phylogenetic results obtained from molecular and conventional data.     

The pathology of ductal-type pancreatic carcinomas and pancreatic intraepithelial neoplasia: Insights for clinicians

The phenotypic classification of pancreatic neoplasms is based on their cellular lineage. Thus, tumors with a ductal, acinar, and endocrine phenotype can be distinguished. Most pancreatic neoplasms show a ductal phenotype and can be classified as ductal adenocarcinomas. Less common tumors with a ductal phenotype are the variants of ductal adenocarcinoma, intraductal papillary mucinous neoplasm (including colloid carcinoma), mucinous cystic neoplasm, medullary carcinoma, and other rare tumors. Ductal adenocarcinomas most likely develop from ductal proliferative lesions arising in the pancreatic duct system. A recently adopted classification system for these lesions distinguishes between three grades of pancreatic intraepithelial neoplasia (PanIN). Molecular studies have revealed that PanIN-2 and PanIN-3 lesions represent a distinct step toward invasive carcinoma.     

Local injection of stem cell factor (SCF) improves myocardial homing of systemically delivered c-kit + bone marrow-derived stem cells

AIMS: Recent studies have shown that stem cell therapy may alleviate the detrimental effects of myocardial infarction. Yet, most of these reports observed only modest effects on cardiac function, suggesting that there still is need for improvement before widespread clinical use. One potential approach would be to increase migration of stem cells to the heart. We therefore tested whether local administration of stem cell factor (SCF) improves myocardial homing of intravenously infused lin-/c-kit+ stem cells after myocardial infarction. METHODS AND RESULTS: Myocardial infarction was induced in mice via ligation of the left anterior descending artery and 2.5 microg of SCF were injected into the peri-infarct zone. Sham-operated mice and animals with intramyocardial injection of phosphate-buffered saline (PBS) served as controls. Twenty-four hours after myocardial infarction, lin-/c-kit+ stem cells were separated from murine bone marrow by magnetic cell sorting, labelled with the green fluorescent cell tracker CFDA or 111 Indium, and subsequently 750 000 labelled cells were systemically infused via the tail vein. Another 24 or 72 h later, respectively (i.e. 48 and 96 h after myocardial infarction), hearts were removed and analysed for myocardial homing of stem cells. Green fluorescent stem cells were exclusively detected in the peri-infarct zone of animals having prior SCF treatment. Radioactive measurements revealed that an intramyocardial SCF injection significantly amplified myocardial homing of lin-/c-kit+ stem cells compared to animals with PBS injections (3.58 +/- 0.53 vs. 2.28 +/- 0.23 cpm/mg/10(6)cpm, +60%, P < 0.05) and sham-operated mice without myocardial infarction (3.58 +/- 0.53 vs. 1.95 +/- 0.22 cpm/mg/10(6)cpm, +85%, P < 0.01). Similar results were obtained 72 h after stem cell injection. CONCLUSION: We demonstrate that intramyocardial administration of SCF sustainably directs more lin-/c-kit+ stem cells to the heart. Future studies will have to show whether higher levels of myocardial SCF (i.e. by virus-mediated gene transfer) can further improve homing of systemically delivered c-kit+ stem cells and thus favourably influence cardiac remodelling following myocardial infarction.