Quantitative in vivo islet potency assay in normoglycemic nude mice correlates with primary graft function after clinical transplantation

Reliable assays are critically needed to monitor graft potency in islet transplantation (IT). We tested a quantitative in vivo islet potency assay (QIVIPA) based on human C-peptide (hCP) measurements in normoglycemic nude mice after IT under the kidney capsule. QIVIPA was initially tested by transplanting incremental doses of human islets. hCP levels in mice were correlated with the number of transplanted islet equivalents (r(2) = 0.6, P<0.01). We subsequently evaluated QIVIPA in eight islet preparations transplanted in type 1 diabetic patients. Conversely to standard criteria including islet mass, viability, purity, adenosine triphosphate content, or glucose stimulated insulin secretion, hCP in mice receiving 1% of the final islet product was correlated to primary graft function (hCP increase) after IT (r(2)=0.85, P<0.01). QIVIPA appears as a reliable test to monitor islet graft potency, applicable to validate new methods to produce primary islets or other human insulin secreting cells.     

Liver Recurrence of a Subcutaneous Temporal Hemangiopericytoma: The Index Case

Introduction  Hemangiopericytoma is an uncommon soft tissue vascular neoplasm. Intraperitoneal hemangiopericytomas such as primary or secondary liver location have been exceptionally described. Its natural history is mostly benign, but recurrences may occur and determining if these late-discovered tumors are distant metastases or synchronous slow and silent-growing locations is sometimes challenging. The histopathological diagnosis and definition of hemangiopericytoma is based on its distinction with solitary fibrous tumors. Liver resection to treat liver hemangiopericytoma seems to be supported by various published experiences. Case presentation  We herein report the first case of liver metastases from a subcutaneous temporal hemangiopericytoma. The patient was treated by a liver resection. CD34 Immunostaining was negative, but strong expression of Bcl2 and CD99 was found in the neoplastic cells. After 1 year of follow-up, the patient is alive without recurrence. Conclusion  To date, published data, including the case herein reported, support the need for a prolonged follow-up and the role of liver resection to treat liver metastases of hemangiopericytomas. Complete resection of all gross disease appears to be the most significant prognostic factor.     

Overexpression of FKBP51 in idiopathic myelofibrosis regulates the growth factor independence of megakaryocyte progenitors

Idiopathic myelofibrosis (IMF) is a chronic myeloproliferative disorder characterized by megakaryocyte hyperplasia and bone marrow fibrosis. Biologically, an autonomous megakaryocyte growth and differentiation is noticed, which contributes to the megakaryocyte accumulation. To better understand the molecular mechanisms involved in this spontaneous growth, we searched for genes differentially expressed between normal megakaryocytes requiring cytokines to grow and IMF spontaneously proliferating megakaryocytes. Using a differential display technique, we found that the immunophilin FKBP51 was 2 to 8 times overexpressed in megakaryocytes derived from patients' CD34(+) cells in comparison to normal megakaryocytes. Overexpression was moderate and confirmed in 8 of 10 patients, both at the mRNA and protein levels. Overexpression of FKBP51 in a UT-7/Mpl cell line and in normal CD34(+) cells induced a resistance to apoptosis mediated by cytokine deprivation with no effect on proliferation. FKBP51 interacts with both calcineurin and heat shock protein (HSP)70/HSP90. However, a mutant FKBP51 deleted in the HSP70/HSP90 binding site kept the antiapoptotic effect, suggesting that the calcineurin pathway was responsible for the FKBP51 effect. Overexpression of FKBP51 in UT-7/Mpl cells induced a marked inhibition of calcineurin activity. Pharmacologic inhibition of calcineurin by cyclosporin A mimicked the effect of FKBP51. The data support the conclusion that FKBP51 inhibits apoptosis through a calcineurin-dependent pathway. In conclusion, FKBP51 is overexpressed in IMF megakaryocytes and this overexpression could be, in part, responsible for the megakaryocytic accumulation observed in this disorder by regulating their apoptotic program.     

Anatomical study of the infra-montanal urethra in man

Five samples infra-montanal prostatic urethra fixed in formalin and stored in liquid nitrogen at -30C were examined histologically. The results of this study demonstrated that muscle fibres of the striated sphincter extend as far as the level of the verumontanum. The proportion of rapid and slow striated fibres was identical. These striated fibres were mixed with smooth muscle fibres of the urethra. The density of innervation of this muscular tunic was found to increase closer to the striated sphincter; it is composed of equal numbers of adrenergic and cholinergic fibres.     

Fluid resuscitation in pre-hospital management of septic shock

Background

Septic shock is associated with hypovolemia resulting in organs failure and poor prognosis. The first step in hemodynamic resuscitation relies on early fluid expansion. In this study, we describe qualitative and quantitative fluid resuscitation of septic shock initially managed in a pre-hospital setting by a mobile intensive care unit.

Endothelial hyperplasia and endothelial galectin-3 expression are prognostic factors in primary central nervous system lymphomas

Recently, considerable attention has been focused on the identification of clinically relevant prognostic markers for primary central nervous system lymphomas (PCNSL). The present study investigated whether three morphological features, i.e. necrosis, reactive perivascular T-cell infiltrate and endothelial hyperplasia, and galectin-1 and galectin-3 immunohistochemical expression have prognostic roles in a series of 58 PCNSL samples from 44 immunocompetent and 14 immunocompromised patients. The presence of endothelial hyperplasia (identified in 21% of the assessable cases) was identified as a bad prognostic factor for immunocompetent PCNSL patients, whereas the other morphological features were not associated with any prognostic value. Lymphomatous cells of eight PCNSL cases expressed galectin-3 without any prognostic value, and lymphomatous cells did not express galectin-1. In contrast, endothelial expression of galectin-3 was identified (by means of uni- and multi-variate analyses) as a bad prognostic factor for immunocompetent PCNSL patients. In addition, a combination of endothelial hyperplasia and/or endothelial galectin-3 expression was shown to be an independent prognostic factor for immunocompetent PCNSL patients treated with methotrexate-based chemotherapy. In summary, this study suggests that endothelial-related markers can identify risk groups of PCNSL patients and indicates that galectin-3 could be involved in PCNSL angiogenesis.