Differentiation of circulating endothelial progenitor cells to a cardiomyogenic phenotype depends on E-cadherin

Progenitor cells may contribute to cardiac regeneration. Here, we investigated the role of cadherins and integrins for differentiation of human adult circulating endothelial progenitor cells (EPCs) into cardiomyocytes (CM) in a co-culture system. N- and E-cadherin were expressed in EPCs and were localized at the interface between EPCs and CM. Incubation of a blocking antibody against E-cadherin reduced the expression of CM marker protein in EPCs. Blocking antibodies against N- or P-cadherin or the beta1- and beta2-integrins were not effective. These data suggested that cell-to-cell communication mediated by E-cadherin contributes to the acquirement of a cardiomyogenic phenotype of human endothelial progenitor cells.     

Human Crossveinless-2 is a novel inhibitor of bone morphogenetic proteins

Drosophila Crossveinless-2 (dCV-2) is required for local activation of Mad phosphorylation in the fruit fly wing and has been postulated to be a positive regulator of BMP-mediated signaling. In contrast, the presence of 5 Chordin-like cysteine-rich domains in the CV-2 protein suggests that CV-2 belongs to a family of well-established inhibitors of BMP function that includes Chordin and Sog [Development 127 (2000) 3947]. We have identified a human homolog of Drosophila CV-2 (hCV-2). Here we show that purified recombinant hCV-2 protein inhibits BMP-2 and BMP-4 dependent osteogenic differentiation of W-20-17 cells, as well as BMP dependent chondrogenic differentiation of ATDC5 cells. Interestingly, hCV-2 messenger RNA is expressed at high levels in human primary chondrocytes, whereas expression in primary human osteoblasts is low. These results suggest that hCV-2 may regulate BMP responsiveness of osteoblasts and chondrocytes in vivo. Taken together we have shown that contrary to the function predicted from the fruit fly, Crossveinless-2 is a novel inhibitor of BMP function.     

Neuroprosthetics of the upper extremity--clinical application in spinal cord injury and future perspectives.

Within the last couple of years, partial restoration of lost motor functions in a larger number of spinal cord injured patients has become possible by the introduction of neuroprostheses into the clinical environment. The Freehand system in particular is the first implantable neuroprosthesis from which a certain group of tetraplegic patients with stable shoulder function, but missing or weak grasp and hold function of the hand do benefit. The system is based on the combination of electrical stimulation and operative tendon transfers and thus represents a multicomponent concept for long-term restoration of the grasp function. The crucial prerequisites for successful use of an implantable neuroprosthesis are the right indication, careful preoperative muscle stimulation, differentiated planning of the surgery and functional training adopted to the individual residual functions. After successful completion of an extensive rehabilitation program, patients are able to use the system for activities of daily living without the need for special additional aids, which enhances their quality of life and independency. In order to extend the group of potential users of neuroprostheses in the future, new technological developments will have to take into account that nowadays the majority of spinal cord injured patients suffer from an incomplete lesion of the spinal cord. For these particular patients who still possess residual functions, modular, "naturally" controllable systems for supporting these functions are needed rather than complex systems to substitute them.     

Is a dietary n-3 fatty acid supplement able to influence the cardiac effect of the psychological stress?

Epidemiological studies suggest that n-3 polyunsaturated fatty acids (PUFA) are involved in the prevention of cardiovascular disease. Stress is known to increase the incidence of CVD and the present study was realised to evaluate some physiological and biochemical effects of dietary docosahexaenoic acid (DHA) in male Wistar rats subjected to a psycho social stress. Rats were fed for 8 weeks a semi-purified diet containing 10% of either sunflower seed oil or the same oil supplemented with DHA. This food supply represented 50% of their daily requirement. The remaining 50% were supplied as 45 mg food pellets designed to induce stress in rats by an intermittent-feeding schedule process. The control group (n = 12) was fed the equivalent food ration as a single daily feeding. The physiological cardiovascular parameters were recorded by telemetry through a transmitter introduced in the abdomen. At the end of the experimentation, the heart and adrenals were withdrawn and the fatty acid composition and the catecholamine store were determined. Dietary DHA induced a pronounced alteration of the fatty acid profile of cardiac phospholipids (PL). The level of all the n-6 PUFAs was reduced while 22:6 n-3 was increased. The stress induced a significant increase in heart rate which was not observed in DHA-fed group. The time evolution of the systolic blood pressure was not affected by the stress and was roughly similar in the stressed rats of either dietary group. Conversely, the systolic blood pressure decreased in the unstressed rats fed DHA. Similar data were obtained for the diastolic blood pressure. The beneficial effect of DHA was also observed on cardiac contractility, since the dP/dt_max increase was prevented in the DHA-fed rats. The stress-induced modifications were associated with an increase in cardiac noradrenaline level which was not observed in DHA-fed rats. The fatty acid composition of adrenals was significantly related to the fatty acid intake particularly the neutral lipid fraction (NL) which incorporated a large amount of DHA. Conversely, n-3 PUFAs were poorly incorporated in adrenal phospholipids. Moreover the NL/PL ratio was significantly increased in the DHA fed rats. The amount of adrenal catecholamines did not differ significantly between the groups. These results show that a supplementation of the diet with DHA induced cardiovascular alterations which could be detected in conscious animals within a few weeks. These alterations were elicited by a reduced heart rate and systolic and diastolic blood pressure.     

Modification of subcellular organelles in pressure-overloaded heart by etomoxir, a carnitine palmitoyltransferase I inhibitor.

To examine the signals regulating cardiac growth and molecular structure of subcellular organelles, cardiac hypertrophy was induced in rats by constriction of the abdominal aorta for 12-13 wk or by treatment with a carnitine palmitoyltransferase I inhibitor, etomoxir (12-15 mg/kg body wt) for 12-13 wk. In contrast to pressure overload, etomoxir redistributed the myosin isozyme population from V3 to V1 and increased the sarcoplasmic reticulum (SR) Ca(2+)-stimulated ATPase activity. When rats with pressure-overloaded hearts were treated with etomoxir, the cardiac hypertrophy was increased whereas the shift in myosin isozymes from V1 to V3 was prevented and the depression in SR Ca(2+)-stimulated ATPase activity was reversed. Plasma thyroid hormone and insulin concentrations were not altered but triglyceride concentrations were reduced in etomoxir-treated rats with pressure overload. The data demonstrate a dissociation between cardiac muscle growth and changes in subcellular organelles and indicate that a shift in myocardial substrate utilization may represent an important signal for molecular remodeling of the heart.     

Fine needle aspiration biopsy in the evaluation of lymphoma presenting as an ovarian and uterine mass

Fine needle aspiration (FNA) was performed in conjunction with frozen section on a patient with primary uterine and ovarian lymphoma. While the frozen section showed evidence of tumor, a diagnosis of lymphoma was not possible on the frozen section alone. The fine needle aspirate showed the tumor to be a lymphoma. In cases of suspected lymphoma, FNA in conjunction with frozen section may be helpful for making the definitive diagnosis.     

Preface

Molecular and Cellular Biochemistry -