The leukemogenicity of Hoxa9 depends on alternative splicing.

Although the transforming potential of Hox genes is known for a long time, it is not precisely understood to which extent splicing is important for the leukemogenicity of this gene family. To test this for Hoxa9, we compared the leukemogenic potential of the wild-type Hoxa9, which undergoes natural splicing, with a full-length Hoxa9 construct, which was engineered to prevent natural splicing (Hoxa9FLim). Inability to undergo splicing significantly reduced in vivo leukemogenicity compared to Hoxa9-wild-typed. Importantly, Hoxa9FLim could compensate for the reduced oncogenicity by collaborating with the natural splice variant Hoxa9T, as co-expression of Hoxa9T and Hoxa9FLim induced acute myeloid leukemia (AML) after a comparable latency time as wild-type Hoxa9. Hoxa9T on its own induced AML after a similar latency as Hoxa9FLim, despite its inability to bind DNA. These data assign splicing a central task in Hox gene mediated leukemogenesis and suggest an important role of homeodomain-less splice variants in hematological neoplasms.

Extreme exercise enhances chromogranin A levels correlating with stress levels but not with cardiac burden.

OBJECTIVE: Stress and heart failure are associated with increased systemic levels of chromogranin A (CGA). Here we analyzed the effects of marathon running on systemic CGA levels and the association with cardiac burden and stress. METHODS: We recruited 47 lean and obese runners for a 10week training program aiming at running a marathon. Heart rates, individual fitness and marathon finishing times were monitored. CGA, proBNP and troponin T levels were analyzed by ELISA. RESULTS: We found a significant increase of CGA (+51%; p<0.01) in lean runners after marathon. The obese group showed the highest troponin T (0.22ng/ml; p<0.01) and proBNP (176.6ng/ml; p<0.01) levels. There were no correlations between proBNP, troponin T and CGA. An inverse correlation (r=-0.45; p<0.01) was found between CGA and finishing times. CONCLUSION: Marathon running is associated with increased CGA levels. However, this does not seem to reflect cardiac burden but rather marathon induced stress.

[Specialised palliative home care (SAPV) in an urban setting--a first year experience]. / Ein Jahr Spezialisierte Ambulante Palliativversorgung (SAPV) im städtischen Ballungsraum.

PROJECT DESCRIPTION: The Palliative Home Care Team of the InterdisciplinaryCenterfor Palliative Medicine at Munich University Hospital has been providing Specialized Home Palliative Care (German abbreviation: SAPV) according to the new German regulations since October 2009. RESULTS: Out of 267 requests, 178 patients were accepted for SAPV, 33 thereof at the level of care coordination and 140 as partial or total home palliative care including 24-h, 7/7 on-call duty. Of the latter group, 90 died at home, 19 in a palliative care unit or hospice and one on a hospital ward.The place of death corresponded to the patients' wishes in 98% of cases. Altogether, emergency medical services other than the SAPV team were called upon in 7 cases, and 12 patients were admitted to a general hospital ward. More than a quarter of our patients had non-oncological diagnoses.The proportion of work dealing with family members (21%) was higher than the patient-related one (19%). The highest percentage (37%) represented office work. CONCLUSIONS: The requirement for SAPV in the urban setting is high, in spite of the intensive primary care, with an increasing proportion of non-oncological patients. A key aspect concerns the work with family members. SAPV can minimize the number of hospital admissions and emergency calls. The patient's wishes concerning the place of death can be fulfilled. Feed-back from patients and family members indicates that SAPV makes an important contribution towards removing the taboo associated with death and dying.

[Modern leukemia diagnosis in adults]. / Moderne Leukämiediagnostik beim Erwachsenen.

Identification of numerous criteria important in the pathogenesis, biology, prognosis and treatment of the different types of leukemia necessitates a broad spectrum of diagnostic methods for the initial diagnosis and in the further course of the disease. In addition to cytomorphology with cytochemistry, which is been path-breaking for the application of further diagnostic methods, cytogenetics has become an obligatory diagnostic tool. Immunophenotyping and, even more relevant, molecular genetics plays an important role. Other diagnostic techniques are widely developed. The diagnostic procedures are described, with a focus on their mode of operation as well as their clinical significance. Because of their high clinical relevance and growing complexity, the diagnosis of leukemias should be performed in specialized laboratories.

The homeobox gene CDX2 is aberrantly expressed and associated with an inferior prognosis in patients with acute lymphoblastic leukemia.

Molecular characterization of acute lymphoblastic leukemia (ALL) has greatly improved the ability to categorize and prognostify patients with this disease. In this study, we show that the proto-oncogene CDX2 is aberrantly expressed in the majority of cases with B-lineage ALL and T-ALL. High expression of CDX2 correlated significantly with the ALL subtype pro-B ALL, cALL, Ph(+) ALL and early T-ALL. Furthermore, high expression of CDX2 was associated with inferior overall survival and showed up as a novel and strong risk factor for ALL in bivariate analysis. Functional analyses showed that overexpression of Cdx2 in murine bone marrow progenitors perturbed genes involved in lymphoid development and that depletion of CDX2 in the human ALL cell line Nalm6 inhibited colony formation. These data indicate that aberrant CDX2 expression occurs frequently and has prognostic impact in adult patients with ALL.

[Do elastic corpuscles appear prenatally? Histological studies of the skin of embryos and fetuses]. / Treten elastische Körperchen bereits pränatal auf? Histologische Untersuchungen an der Haut von Embryonen und Feten.

There have been descriptions of corpuscular structures in the human skin since the turn of the century. These bodies 3-20 micron in size are situated in the zone connecting the epidermis and corium. They can be readily visualized with resorcinol-fuchsin staining according to Weigert and are regarded as morphological variants of the elastic fiber system. According to the investigations we have carried out so far on the skin of babies, infants and adults, these elastic globes exhibit the following distribution pattern: abundant occurrence on the limbs, only scanty occurrence on the trunk and the hands. With increasing age, a numerical increase of elastic globes can be demonstrated in babies and in infants. In adults, there is an opposite tendency in the hands and feet. Here, the frequency of elastic globes decreases with increasing age. To clarify the question as to whether precursors of elastic globes are present, the skin of 35 embryos and fetuses was systematically examined for their occurrence and the results of the investigation are discussed.