a-chromatin-immunoprecipitation-assay-to-identify-novel-nfat2-target

A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is characterized by the expansion of malignant B cell clones and represents the most common leukemia in western ...

University of Tübingen

Multiple symmetric lipomatosis: a paradigm of metabolically innocent obesity?

To assess standardized whole body adipose tissue topography in a cohort of subjects at an increased risk for type 2 diabetes and to compare fat distribution in subgroups regarding anthropometric (age, body mass index [BMI]) and metabolic parameters (insulin sensitivity).

Standardized assessment of whole body adipose tissue topography by MRI.

Epitheloid hemangioendothelioma is a rare malignant tumor which can involve bones, liver, lungs, kidneys, deep soft tissue, muscles, dermis, and central nervous system. Multifocal disease occurs in 10% of the cases. The clinical presentation results from occlusion of small blood vessels due to the disease itself or as a paraneoplastic syndrome.

Disseminated epitheloid hemangioendothelioma mimicking symptoms of systemic vasculitis.

In humans, low plasma adiponectin concentrations precede a decrease in insulin sensitivity and predict type 2 diabetes independently of obesity. However, it is possible that the contribution of adiponectin to insulin sensitivity is not equally strong over the whole range of obesity.

The association between plasma adiponectin and insulin sensitivity in humans depends on obesity.

A hypercalcemic crisis is a life-threatening disease with multiorgan failure due                     to severe hypercalcemia. If left untreated, a hypercalcemic crisis is associated                     with a very high mortality and requires immediate diagnostic and therapeutic                     interventions. Especially a rapid rise to high calcium levels impairs the                     function of several organ systems and leads to central nervous, renal,                     cardiovascular and gastrointestinal symptoms. A hypercalcemic crisis is caused                     in more than 90 % by malignancy or primary hyperparathyreoidism and only in very                     rare cases by other diseases such as granulomatous diseases or other                     endocrinological diseases. Causal therapeutic options include an adequate                     treatment of malignancy and a surgical resection of the adenomatous tissue in                     primary hyperparathyreoidism. In addition, an adequate supportive therapy to                     lower calcium levels should be initiated as soon as possible. Rehydration with                     normal saline is the mainstay of therapy. Additional pharmacological therapies                     include biphosphonates, loop diuretics, calcitonin, steroids and calcimimetics.                     Besides classic hemodialysis continous renal replacement therapy with citrate                     anticoagulation is new therapeutical approach that can be used for the acute                     reduction of elevated serum calcium levels.

[Hypercalcemic crisis in intensive care].

Rhabdomyolysis is associated with the release of myoglobin into the circulation, promoting acute kidney injury (AKI). In severe rhabdomyolysis, dialysis-dependent AKI doubles mortality. Standard blood purification techniques have limited efficacy in removing myoglobin. We describe high cut-off (HCO) renal replacement therapy (RRT) as a novel approach for extracorporeal elimination of myoglobin in rhabdomyolysis-associated AKI.

High cut-off renal replacement therapy for removal of myoglobin in severe rhabdomyolysis and acute kidney injury: a case series.

Aim of the study was to compare the short-term effects of oxygen therapy via a high-flow nasal cannula (HFNC) on functional and subjective respiratory parameters in patients with acute hypoxic respiratory failure in comparison to non-invasive ventilation (NIV) and standard treatment via a Venturi mask.

Nasal high-flow oxygen therapy in patients with hypoxic respiratory failure: effect on functional and subjective respiratory parameters compared to conventional oxygen therapy and non-invasive ventilation (NIV).

Aim of this study was to reduce blood loss caused by diagnostic blood sampling and to minimize the development of anemia in a high-risk group of mechanically ventilated medical intensive care patients. We therefore implemented a "blood-saving bundle" (BSB) combining a closed-loop arterial blood sampling system, smaller sampling tubes, reduced frequency of blood drawings, and reduced sample numbers.

A Simple "Blood-Saving Bundle" Reduces Diagnostic Blood Loss and the Transfusion Rate in Mechanically Ventilated Patients.

Chronic lymphocytic leukaemia (CLL) is a clonal disorder of mature B cells. Most patients are characterised by an indolent disease course and an anergic phenotype of their leukaemia cells, which refers to a state of unresponsiveness to B cell receptor stimulation. Up to 10% of CLL patients transform from an indolent subtype to an aggressive form of B cell lymphoma over time (Richter´s syndrome) and show a significantly worse treatment outcome. Here we show that B cell-specific ablation of Nfat2 leads to the loss of the anergic phenotype culminating in a significantly compromised life expectancy and transformation to aggressive disease. We further define a gene expression signature of anergic CLL cells consisting of several NFAT2-dependent genes including Cbl-b, Grail, Egr2 and Lck. In summary, this study identifies NFAT2 as a crucial regulator of the anergic phenotype in CLL.NFAT2 is a transcription factor that has been linked with chronic lymphocytic leukaemia (CLL), but its functions in CLL manifestation are still unclear. Here the authors show, by analysing mouse CLL models and characterising biopsies from CLL patients, that NFAT2 is an important regulator for the anergic phenotype of CLL.

NFAT2 is a critical regulator of the anergic phenotype in chronic lymphocytic leukaemia.

Castleman's disease (CD) is a rare lymphoproliferative disorder with its distinct unicentric (uCD) and multicentric (mCD) entities. The present work aimed at characterizing CD in more detail. From the 775 articles found by a PubMed search, 1133 cases were extracted. Two own cases were included. UCD was identified in 719 (42% males) and mCD in 416 (63% males) cases. Age in uCD was 34±17 and in mCD 48±18years. The hyaline-vascular type predominated in uCD and the plasma cell type in mCD. Clinical symptoms were more common in mCD. The head and neck region was most frequently affected in uCD and the axillary region in mCD. Prevalence of human immunodeficiency virus (HIV) and human herpesvirus-8 (HHV-8) positivity was higher in mCD. In CT scans, high contrast enhancement and calcifications were more frequent in uCD (all p<0.0001). The two forms of CD not only differ markedly in their clinical, laboratory and imaging findings, but also in treatment response and prognosis.

Clinical, laboratory and imaging findings in Castleman's disease - The subtype decides.

Nonadherence to standard operating procedures (SOPs) during handling and processing of whole blood is one of the most frequent causes affecting the quality of serum and plasma. Yet, the quality of blood samples is of the utmost importance for reliable, conclusive research findings, valid diagnostics, and appropriate therapeutic decisions.

Quality Control of Serum and Plasma by Quantification of (4E,14Z)-Sphingadienine-C18-1-Phosphate Uncovers Common Preanalytical Errors During Handling of Whole Blood.

Long-term remission of refractory Rosai-Dorfman disease after salvage therapy with clofarabine in an adult patient.

Adequate nutrition therapy in critically ill patients poses a challenge because of the variable energy and substrate needs. The objective was to investigate whether nutrition therapy involving indirect calorimetry (IC), instead of equations for assessment of energy needs, could improve the nutrition status of critically ill patients.

Optimization of Nutrition Therapy with the Use of Calorimetry to Determine and Control Energy Needs in Mechanically Ventilated Critically Ill Patients: The ONCA Study, a Randomized, Prospective Pilot Study.

Article	Year
Multiple symmetric lipomatosis: a paradigm of metabolically innocent obesity? Diabetes care\| PubMed ID: 14988304	2004
Standardized assessment of whole body adipose tissue topography by MRI. Journal of magnetic resonance imaging : JMRI\| PubMed ID: 15778954	2005
Disseminated epitheloid hemangioendothelioma mimicking symptoms of systemic vasculitis. Onkologie\| PubMed ID: 16160406	2005
The association between plasma adiponectin and insulin sensitivity in humans depends on obesity. Obesity research\| PubMed ID: 16286515	2005
[Hypercalcemic crisis in intensive care]. Deutsche medizinische Wochenschrift (1946)\| PubMed ID: 22588655	2012
High cut-off renal replacement therapy for removal of myoglobin in severe rhabdomyolysis and acute kidney injury: a case series. Nephron. Clinical practice\| PubMed ID: 23327834	2012
Nasal high-flow oxygen therapy in patients with hypoxic respiratory failure: effect on functional and subjective respiratory parameters compared to conventional oxygen therapy and non-invasi... BMC anesthesiology\| PubMed ID: 25110463	2014
A Simple "Blood-Saving Bundle" Reduces Diagnostic Blood Loss and the Transfusion Rate in Mechanically Ventilated Patients. PloS one\| PubMed ID: 26421920	2015
NFAT2 is a critical regulator of the anergic phenotype in chronic lymphocytic leukaemia. Nature communications\| PubMed ID: 28970470	2017
Clinical, laboratory and imaging findings in Castleman's disease - The subtype decides. Blood reviews\| PubMed ID: 29223447	2018
Quality Control of Serum and Plasma by Quantification of (4E,14Z)-Sphingadienine-C18-1-Phosphate Uncovers Common Preanalytical Errors During Handling of Whole Blood. Clinical chemistry\| PubMed ID: 29567661	2018
Long-term remission of refractory Rosai-Dorfman disease after salvage therapy with clofarabine in an adult patient. Annals of hematology\| PubMed ID: 29980874	2018
Optimization of Nutrition Therapy with the Use of Calorimetry to Determine and Control Energy Needs in Mechanically Ventilated Critically Ill Patients: The ONCA Study, a Randomized, Prospect... JPEN. Journal of parenteral and enteral nutrition\| PubMed ID: 30251255	2018

Michael Haap

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