[Clinical research in the "acute and chronic leukemias"competence network ].
Goal of the network is the construction of an exemplary cooperative leukemia network for the improvement of medical care and of health related research in acute and chronic leukemias. This is achieved by improved mechanisms of cooperation among all major groups in Germany that deal with the leukemias in research and in patient care. In practice, cooperation between clinical groups and scientists in research institutes is mediated by various instruments that improve communication, flow of information and interdisciplinary cooperation and also increase information transfer from top research institutions to clinical translation. The network comprises more than 1400 participants in about 400 university centers, large community hospitals and specialty practices with functional communication structures, interdisciplinary cooperation and nation-wide logistics. The improved cooperation and the accelerated information transfer from the bench to the "bedside" results in an added value that ultimately results in improved survival results of patients and in superior competitiveness of involved research workers and clinicians. Sustainability is addressed by establishing a leukemia foundation to support long term financial coverage of the network and by negotiating a proposal for a European Network of Excellence against leukemia within the Sixth Framework Programme of the European Union.


Smooth muscle cell of the canine prostate in spontaneous benign hyperplasia, steroid induced hyperplasia and estrogen or tamoxifen treated dogs.
Human benign prostatic hyperplasia is a predominantly stromal hyperplasia with accumulation of connective tissue. The main ultrastructural finding, which may be causal, is an activation of the smooth muscle cells, as seen by an increase of the volume density of the organelles within these cells. The dog is widely used as an animal model for human prostatic hyperplasia in spite of several differences. In this work the smooth muscle cells of the spontaneous and steroid-induced (by treating castrates with dihydrotestosterone and estradiol) prostatic hyperplasia of dogs were analysed by electron microscopical morphometry, and compared to estrogen or tamoxifen (antiestrogen) treated dogs as well as to untreated or castrated control dogs. The results clearly show that the prostatic smooth muscle cells of the dog can be activated by estrogen as well as tamoxifen, which proves the estrogenic side activity of the latter. In marked contrast to that, neither in the spontaneous nor in the steroid-induced prostatic hyperplasia could an activation of the smooth muscle cells be found. This is a most important difference from human benign prostatic hyperplasia, which limits the use of this animal model, and it might even be the explanation of the different reaction of human and canine prostatic hyperplasia to therapeutic hormonal manipulations.


Impact of maternal nutrition during early pregnancy and diet during lactation on lactoferrin in mature breast milk.
Lactoferrin supplementation is a promising strategy to prevent infections in neonates. Exploring whether maternal nutritional status in early pregnancy and maternal diet during lactation are associated with lactoferrin concentrations in mature human milk can provide early warning and allow timely adjustment. In this follow-up cohort study, 206 participants were recruited at Peking University People's Hospital from June 2018 to June 2019. The levels of albumin and thyroid-stimulating hormones (TSH) were determined as nutritional indicators during early pregnancy. Information on maternal diet during lactation was collected with a semiquantitative food frequency questionnaire, and the lactoferrin concentrations in breast milk were examined at around 42 d postpartum. The median level (interquartile range) of lactoferrin in breast milk was 2844.2 (2568.1, 3103.1) μg/mL. Overall, 5.5% of participants had lower albumin (<40 g/L), and 21.6% had elevated TSH (>2.5 mIU/L), respectively. The concentration of lactoferrin was higher (216.8 [13.4, 420.2] μg/mL) in women with lower albumin levels than in those with normal levels, and elevated TSH had no effect. A 1 g increase in egg intake led to a 0.3 (0.0, 0.6) μg/mL increase in lactoferrin concentration. Lactoferrin levels were also affected by intake of energy, protein, cholesterol, and vitamin A. Women with lower albumin levels in early pregnancy had higher levels of lactoferrin in mature breast milk. TSH was not related to lactoferrin levels. Intake of energy, protein, cholesterol, and vitamin A may have contributed to lactoferrin concentrations in milk, and egg intake was positively associated with lactoferrin.


Toxicity of tire particle leachates on early life stages of keystone sea urchin species.
Particles from tires are a major fraction of microplastic pollution. They contain a wide range of chemical additives that can leach into the water and be harmful to aquatic organisms. In this study, we investigated the acute toxicity of tire particle leachates in early life stages of three keystone echinoderm species (Paracentrotus lividus, Arbacia lixula, Diadema africanum). Embryos were exposed for 72 h to a range of leachate dilutions, prepared using a concentration of 1 g L-1. Larval growth, abnormal development, and mortality were the measured endpoints. Furthermore, we estimated the activity of glutathione S transferase (GST) and the electron transport system (ETS) in P. lividus. Strong concentration-dependent responses were observed in all species, though with differing sensitivity. The median effect concentrations for abnormal development in P. lividus and A. lixula were 0.16 and 0.35 g L-1, respectively. In D. africanum, mortality overshadowed abnormal development and the median lethal concentration was 0.46 g L-1. Larvae of P. lividus were significantly smaller than the control from 0.125 g L-1, while the other two species were affected from 0.5 g L-1. ETS activity did not change but there was a non-significant trend of increasing GST activity with leachate concentration in P. lividus. Seven organic chemicals and eight metals were detected at elevated concentrations in the leachates. While we regard zinc as a strong candidate to explain some of the observed toxicity, it can be expected that tire particle leachates exhibit a cocktail effect and other leached additives may also contribute to their toxicity. Our results emphasize the importance of multi-species studies as they differ in their susceptibility to tire particle pollution. We found negative effects at concentrations close to projections in the environment, which calls for more research and mitigation actions on these pollutants.


Species identification of epidermal cells in the human skin/nude mouse model with lectins.
A series of lectins were examined in order to find suitable epidermal species markers for the human skin/nude mouse model. In histological sections of formalin-fixed and paraffin-embedded material it was found that the lectins GSA I and PNA could serve as suitable markers for murine and human epidermis, respectively.


Folate metabolic pathway single nucleotide polymorphisms: a predictive pharmacogenetic marker of methotrexate response in Indian (Asian) patients with rheumatoid arthritis.
We evaluated the pharmacogenetic influence of genetic polymorphisms in folate pathway genes in Indian rheumatoid arthritis patients receiving methotrexate (MTX). Twelve polymorphisms within nine folate pathway genes were analyzed for association with MTX response in 322 Indian rheumatoid arthritis (RA) patients and MTX pharmacokinetics in 94 RA patients. Polymorphisms in GGH, SHMT1 and TS were associated with MTX-related adverse events while SNPs in MTHFR and RFC1/SLC19A1 were associated with MTX efficacy. TS5'UTR and SHMT1 polymorphisms were associated with higher plasma levels of MTX. Polymorphisms in folate-MTX pathway genes contribute to MTX response and affect MTX concentrations in Indian RA patients. A toxicogenetic index could identify patients who develop adverse events to MTX.


Suppurative gastritis in BALB/c mice infected with Listeria monocytogenes via the intragastric route.
Suppurative gastritis was demonstrated in BALB/c mice 3 days after intragastric inoculation with 10(9) organisms of Listeria monocytogenes strain ATCC19113 (serotype 3). Also tested were four other strains of mice (C3H, C57BL/6, FVB and ICR) and three other strains of L. monocytogenes (HPB 3 [serotype 4b], HPB 410 [serotype 1/2a] and HPB 503 [serotype 1/2b]). After inoculation with ATCC19113 the numbers of bacteria found in the stomach wall were greater in C57BL/6 and ICR mice than in C3H and FVB mice; moreover, the gastritis produced in BALB/c and C57BL/6 mice was more severe than that produced in the other mouse strains. The gastritis produced in BALB/c mice with L. monocytogenes HPB 3, HPB 410 and HPB 503 was much more severe than that produced by ATCC19113. The inflammatory response occurred in the lamina muscularis and mucosa of the fundus. Massive necrosis of the gastric epithelium was observed, and there was oedema in a large part of the mucosal layer of the fundus. In addition, the submucosal layer was apparently expanded due to oedema, and in the cardia, the mucosal layer had become thin and flattened. Immunohistochemically, a polyclonal antibody against Listeria spp. produced labelling in areas of the gastric mucosa in which there was an inflammatory response and gastric epithelial necrosis.