Diminished met signaling in podocytes contributes to the development of podocytopenia in transplant glomerulopathy.

Transplant glomerulopathy (TxG) can show secondary focal and segmental glomerulosclerosis (FSGS). FSGS in native kidneys is caused by podocytopenia. This study examines podocytopenia and the role of decreased paracrine Met activation on podocytes by decreased glomerular hepatocyte growth factor (HGF) levels in the development of podocytopenia in TxG.

Obliterative airway remodeling: molecular evidence for shared pathways in transplanted and native lungs.

Obliteration of the small airways is a largely unresolved challenge in pulmonary medicine. It represents either the irreversible cause of functional impairment or a morphologic disorder of limited importance in a multitude of diseases. Bronchiolitis obliterans is a key complication of lung transplantation.

ADAMTS13--marker of contractile phenotype of arterial smooth muscle cells lost in benign nephrosclerosis.

Background: Hypertensive nephrosclerosis alone and in combination with other renal diseases is a leading cause of terminal renal insufficiency. Histologic lesions manifest as benign nephrosclerosis (bN) with arteriolar hyalinosis and later fibrosis. Procoagulant micromilieus have been implicated in fibrosis.

Obliterative airway remodelling in transplanted and non-transplanted lungs.

Obliterative airway remodelling is a morphological sequence in a variety of pulmonary diseases. Notably, bronchiolitis obliterans represents one of the key complications of lung transplantation, induced by (immigrating) myofibroblasts. A comparative expression analysis of obliterative airway remodelling in transplanted and non-transplanted patients has not been reported so far.

Aberrant microRNA expression pattern in myelodysplastic bone marrow cells.

The microRNA/miR system might contribute to deregulation of cell homeostasis/disease phenotype. This is the first approach to generate an expression profile of 365 microRNAs in myelodysplastic syndromes (MDS) with normal karyotype (n=12) and distinct cytogenetic aberrations (n=12). In MDS-del(5q), a series of microRNAs not in the 5q-region was increased.

"Hypoxia-induced down-regulation of microRNA-449a/b impairs control over targeted SERPINE1 (PAI-1) mRNA - a mechanism involved in SERPINE1 (PAI-1) overexpression".

Background: In damaged organs tissue repair and replacement of cells by connective tissue provokes a response of fibroblasts to cellular stress factors such as hypoxia.MicroRNAs (miRNA) are small non-coding RNA molecules which bind to their mRNA targets which eventually lead to repression of translation. Whether the response of fibroblasts to stress factors also involves the miRNA system is largely unknown.

MicroRNA expression profiling of megakaryocytes in primary myelofibrosis and essential thrombocythemia.

In primary myelofibrosis (PMF) and essential thrombocythemia (ET) the megakaryocytic lineage characteristically shows aberrant proliferation and maturation in which the regulatory microRNA (miR) system might be involved. Laser-microdissected PMF and ET megakaryocytes were analysed with real-time polymerase chain reaction (PCR) low density arrays comprising 365 microRNAs. The highest megakaryocytic expression levels were observed for miR-223, which is known to be expressed also in granulopoiesis.

JAK2(V617F) allele burden discriminates essential thrombocythemia from a subset of prefibrotic-stage primary myelofibrosis.

Objective: Among Philadelphia chromosome-negative myeloproliferative neoplasms (Ph(-) MPN), essential thrombocythemia (ET) and the prefibrotic phase of primary myelofibrosis (PMF) represent two subtypes with considerable overlap.

Materials And Methods: In this study, histopathological classification of 490 MPN cases was correlated with the allelic burden of JAK2(V617F) and MPL(W515L).

Results: Ph(-) MPN entities largely overlap with regard to JAK2(V617F) and MPL(W515L) allele burden, but ET displayed mutant allele burden <50%.

Significant inverse correlation of microRNA-150/MYB and microRNA-222/p27 in myelodysplastic syndrome.

We investigated whether, in myelodysplastic syndromes (MDS), aberrant expression of miR-150/miR-221/miR-222 and their designated target mRNA molecules MYB, p27 and c-KIT may be involved in insufficient haematopoiesis. In a series of MDS (n=52), an aberrant increase of miR-150 was found only in MDS with associated del(5q) (n=9; p<0.01).

Identification of new target molecules PTK2, TGFBR2 and CD9 overexpressed during advanced bone marrow remodelling in primary myelofibrosis.

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by remodelling of the bone marrow, including progressive myelofibrosis and exaggerated angiogenesis. Advanced PMF frequently shows a full-blown fibre meshwork, which avoids aspiration of cells, and the expression profile of genes related to stroma pathology at this stage remains largely undetermined. We investigated bone marrow core biopsies in PMF showing various degrees of myelofibrosis by custom-made low density arrays (LDA) representing target genes with designated roles in synthesis of extracellular matrix, matrix remodelling, cellular adhesion and motility.

Expression of adhesion factor CD239 in bone marrow cells in chronic myeloproliferative diseases.

Patients suffering from Philadelphia chromosome-negative chronic myeloproliferative disease (Ph(-) CMPD), such as polycythaemia vera (PV), are frequently JAK2(V617F)-mutated and have an elevated risk for thromboembolic complications. Recent data indicated that the molecular basis of JAK2(V617F) and thrombosis might be related to increased expression of CD239, the Lutheran blood group/basal cell adhesion molecule, in PV-derived red blood cells. The aim of this study was to clarify whether JAK2(V617F) PV with thromboembolism is characterised by CD239 overexpression.

Expression profiling of apoptosis-related genes in megakaryocytes: BNIP3 is downregulated in primary myelofibrosis.

Objective: In order to identify factors involved in the aberrantly regulated apoptosis of megakaryocytes in primary myelofibrosis (PMF), the mRNA expression of human megakaryocytes in situ was quantified by real-time polymerase chain reaction low-density arrays.

Materials And Methods: The mRNA from 200 to 300 laser-microdissected megakaryocytes per case from PMF (n=22) and control (n=10) bone marrow was reverse-transcribed into cDNA by random priming and subsequently amplified by primer-specific cDNA amplification. The mRNA of corresponding total bone marrow cells was reverse-transcribed into cDNA without the following amplification.

Megakaryocytic expression of miRNA 10a, 17-5p, 20a and 126 in Philadelphia chromosome-negative myeloproliferative neoplasm.

Micro RNA (miRNA) are small non-coding RNA molecules which have a post-transcriptional inhibitory regulation function, e.g. in megakaryopoiesis.

Amplification of mRNA from laser-microdissected single or clustered cells in formalin-fixed and paraffin-embedded tissues for application in quantitative real-time PCR.

The determination of marker genes and gene clusters involved in disease pathogenesis is increasingly contingent on high-throughput methods of gene expression profiling. However, the concurrently increasing application of mRNA from formalin-fixed and paraffin-embedded (FFPE) tissue archives, as well as cell-type-specific approaches by laser-assisted microdissection, frequently results in very small and degraded quantities of RNA. Therefore, a successful amplification of cell-type-specific mRNA targets from FFPE tissues becomes more and more essential.

Bone morphogenetic proteins are overexpressed in the bone marrow of primary myelofibrosis and are apparently induced by fibrogenic cytokines.

Primary myelofibrosis (PMF) is a myeloproliferative neoplasia characterized by progressive deposition of extracellular matrix components in the bone marrow. The involvement of members of the bone morphogenetic protein (BMP) family in aberrant bone marrow matrix homeostasis in PMF has not yet been investigated. Therefore, we analyzed expression of BMP1, an activator of latent transforming growth factor beta-1 (TGFbeta-1) and processor of collagen precursors, and other BMPs in bone marrow from PMF patients and controls (n = 95).

In situ mapping of nitrifiers and anammox bacteria in microbial aggregates by means of confocal resonance Raman microscopy.

In the present work the exploration of microbial communities by confocal resonance Raman microscopy (CRRM) is reported. Using the resonance Raman effect of cytochrome c (Cyt c) we were able to record the microbial distribution of nitrifiers and anammox bacteria directly in their natural environment without the need of sample preparation. For this new non-invasive investigation a reference database of bacteria assumed to be found in microbial aggregates obtained from biological wastewater treatment was created.

The expression levels of telomerase catalytic subunit hTERT and oncogenic MYC in essential thrombocythemia are affected by the molecular subtype.

The role of telomerase catalytic subunit hTERT in clonal malignancies including human leukemia is fundamental in overcoming cell senescence and enabling prolonged proliferation. One direct transcriptional activator of hTERT is the oncogene MYC which is known to be, in turn, activated by JAK2. To explore the relationship of telomerase, MYC and JAK2 in chronic myeloproliferative diseases, we investigated hTERT and MYC expression in bone marrow cells of essential thrombocythemia (ET) and polycythemia vera (PV).