Interaction of prolactin, ANPergic, oxytocinergic and adrenal systems in response to extracellular volume expansion in rats

The present study evaluated the effect of acute extracellular volume expansion (EVE) induced by intravenous injection of isotonic (0.15 m NaCl) or hypertonic saline (0.3 m NaCl) on prolactin, corticosterone, vasopressin, oxytocin and atrial natriuretic peptide (ANP) secretion. Male Wistar rats were treated with bromocriptine, sulpiride or dexamethasone. After isotonic and hypertonic EVE, the control group showed a significant increase in the plasma concentrations of prolactin, corticosterone, ANP and oxytocin. The increase in ANP and oxytocin levels in response to hypertonic EVE was more pronounced than to isotonic EVE. Bromocriptine and sulpiride treatments did not modify corticosterone, ANP and oxytocin responses to either isotonic or hypertonic EVE. The increases in prolactin and oxytocin, but not ANP, were blocked in dexamethasone pretreated rats. In conclusion, isotonic or hypertonic EVE induced an increase in the plasma concentrations of prolactin, corticosterone, ANP and oxytocin. The increases in ANP and oxytocin were independent of plasma concentrations of prolactin. The increases in prolactin and oxytocin were blocked by the inhibition of the hypothalamo-pituitary-adrenal (HPA) axis by dexamethasone. However, dexamethasone did not alter the increase in ANP secretion induced by isotonic or hypertonic EVE. Therefore, prolactin might participate in regulation of the hydroelectrolytic balance in mammals; however, in the present study, there was no evidence for direct interaction with ANPergic and oxytocinergic systems. In addition, the responses of prolactin and oxytocin induced by isotonic or hypertonic EVE are modulated by the HPA axis.     

Diversity of genomic breakpoints in TFG-ALK translocations in anaplastic large cell lymphomas: identification of a new TFG-ALK(XL) chimeric gene with transforming activity

Anaplastic large cell lymphomas are associated with chromosomal aberrations involving the anaplastic lymphoma kinase (ALK) gene at 2p23 that result in the expression of novel chimeric ALK proteins with transforming properties. In most of these tumors, the t(2;5)(p23;q35) generates the NPM-ALK fusion gene. However, several studies have now demonstrated that genes other than NPM may be fused to the ALK gene. We have recently described two different ALK rearrangements involving the TRK-fused gene (TFG) in which the same portion of ALK was fused to different length fragments of the 5' TFG region. These two rearrangements encoded chimeric proteins of 85 kd (TFG-ALK(S)) and 97 kd (TFG-ALK(L)), respectively. In this study, we have identified a new ALK rearrangement in which the catalytic domain of ALK was fused to a larger fragment of the TFG gene (TFG-ALK(XL)), encoding for a fusion protein of 113 kd. Genomic analysis of these three TFG-ALK rearrangements revealed that the TFG breakpoints occur at introns 3, 4, and 5, respectively, whereas the ALK breakpoints always occur in the same intron. No homologous regions or known recombination sequences were found in these regions. Transfection experiments using NIH-3T3 fibroblasts showed a similar transforming efficiency of TFG-ALK variants compared with NPM-ALK. In addition, in common with NPM-ALK, the TFG-ALK proteins formed stable complexes with the signaling proteins Grb2, Shc, and PLC-gamma. In conclusion, these findings indicate that the TFG may use a variety of intronic breakpoints in ALK rearrangements generating fusion proteins of different molecular weights, but with similar transforming potential than NPM-ALK.     

Mantle Cell Lymphomas Lack Expression of p27kip1, a Cyclin-Dependent Kinase Inhibitor

p27^Kip1 is a cyclin-dependent kinase inhibitor that regulates the decision to enter S phase or withdraw from the cell cycle. In resting cells, the level of p27^Kip1 provides an inhibitory threshold above which G1 cyclin D/E/cyclin-dependent kinases accumulate before activation; however, in cycling cells, p27^Kip1 protein is sequestered by high levels of active cyclin D/cyclin-dependent kinase 4 complexes. As a group, the cyclin-dependent kinase inhibitors have been proposed to act as tumor suppressor genes, and several members have been implicated in the pathogenesis of a variety of human cancers. We examined p27^Kip1 expression in 116 non-Hodgkin’s lymphomas including 50 cases of MCL (40 typical and 10 blastic variants), 21 follicular lymphomas, 20 diffuse large B-cell lymphomas, 16 chronic lymphocytic leukemias, 8 marginal zone B-cell lymphomas, and 1 splenic marginal zone lymphoma, and correlated its expression with that of the proliferation marker Ki67 (MiB1) and with p53. p27^Kip1gene structure was analyzed by Southern blot in the group of MCLs. In all cases of non-Hodgkin’s lymphoma other than MCL, p27^Kip1 expression was inversely related to the proliferation index as measured by Ki67. In contrast, in typical MCL, p27^Kip1 expression was negative in 35 of 40 (88%) cases, irrespective of the proliferative rate (median 15%; range 2 to 90%). Paradoxically, in the blastic variant of MCL, 8 of 10 (80%) cases showed expression of p27^Kip1, despite a high proliferation rate (median 60%; range 32 to 100%). However, the staining in most of the cases was less intense than in the reactive T lymphocytes. Deletions of p27^Kip1gene were not found in any of the 25 cases examined. p53 expression was found in 15 of 50 cases of MCL: 7 of 10 (70%) in the blastic variant and 8 of 40 (20%) in the typical MCL (70% vs. 20%, P < 0.0045). These results demonstrate that MCLs, in contrast to other non-Hodgkin’s lymphomas and normal lymphoid tissue, fail to correlate p27^Kip1 expression with the proliferation rate. This peculiar uncoupling of p27^Kip1 protein expression from the proliferation rate may be related to the high levels of cyclin D1 expressed in MCL and is likely to have profound effects on cell cycle regulation and contribute to the pathogenesis of MCL.     

Large left atrial myxoma presented as fever of unknown origin: a challenging diagnosis and a review of the literature

Myxoma is the most common type of primary tumors of the heart in adults. The majority of patients with myxomas may experience symptoms due to central or peripheral embolism or intracardiac obstruction, while in some cases, they may be completely asymptomatic. Rarely, patients develop unusual symptoms that complicate the diagnostic evaluation. Herein, we describe the case of a 70-year-old patient with a long-lasting low-grade fever due to a large left atrial myxoma revealed during a transthoracic echocardiography.     

Schistosomiasis: an unusual cause of tubal infertility

A case report of a Nigerian woman having an unusual cause oftubal infertility is presented. On histological examinationof the Fallopian tube, ova of Schistosoma haematobium enclosingliving miracidia were found in the smooth muscle layer of theFallopian tube and its mesosalpinx. Mechanisms of tubal involvementare analysed. The case indicates the need to consider schisto-somiasisas a possible aetiological factor in patients with tubal infertilitycoming from areas where the disease is endemic.