Biomedical subjects
Publications and source records attributed to G Leone.
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The behaviour of the factor VIII/von Willebrand factor complex (VIII:C, VIIIR:Ag and VIIIR:RCof) was investigated in 23 patients with secretory myeloma, in 2 patients with non-secretory myeloma and in 5 patients with macroglobulinemia. In most patients (21 of 25 patients with plasma cell myeloma and 2 of 5 patients with macroglobulinemia) VIIIR:Ag was increased usually without corresponding increases in VIII:C and VIIIR:RCof. There was no correlation between the VIIIR:Ag levels and paraprotein Ig type or level nor with the presence or the absence of Bence Jones proteins in serum and urine. Furthermore, increased levels of VIIIR:Ag were found in patients with non-secretory myeloma. In general, VIIIR:Ag was higher in patients with extensive bone lesions and there was a significant correlation between cell mass and the VIIIR:Ag level. The crossed-immunoelectrophoresis of plasmas with discrepant VIIIR:Ag and VIIIR:RCof showed variation from the normal pattern.
Two cases of acute myeloid leukemia (AML) presenting with bulky adenopathy are reported. Both patients were febrile at admission and showed massive and diffuse lymph node involvement, hepatomegaly, and splenomegaly. Erythematopapular leukemic skin lesions were present in one case at the onset and developed in the other at the time of relapse. Anemia, thrombocytopenia, and moderate leukocytosis were present in both. The presence of immature cells in peripheral blood and bone marrow allowed a rapid diagnosis of AML, FAB M1, in one patient. In the other case, owing to the paucity of immature cells in peripheral blood and bone marrow, lymph node biopsy with histology, imprint cytology, and immunocytochemistry were essential for the diagnosis (AML, FAB M2, with trilineage dysplasia and basophilic involvement). Both patients achieved complete remission (CR), followed by an early relapse 3 months later. They underwent allogeneic bone marrow transplantation (BMT) from HLA identical siblings. One patient is actually alive and in CR at 6 months after BMT; the other patient showed a leukemic regrowth after transplantation and died 4 months later.
We evaluated the influence of prolonged weightlessness on the performance of visual tasks in the course of the Russian-French missions ANTARES, Post-ANTARES and ALTAIR aboard the MIR station. Eight cosmonauts were subjects in two experiments executed pre-flight, in-flight and post-flight sessions. In the first experiment, cosmonauts performed a task of symmetry detection in 2-D polygons. The results indicate that this detection is locked in a head retinal reference frame rather than in an environmentally defined one as meridional orientations of symmetry axis (vertical and horizontal) elicited faster response times than oblique ones. However, in weightlessness the saliency of a retinally vertical axis of symmetry is no longer significantly different from an horizontal axis. In the second experiment, cosmonauts performed a mental rotation task in which they judged whether two 3-D objects presented in different orientations were identical. Performance on this task is basically identical in weightlessness and normal gravity.
BACKGROUND AND AIMS: Because of their plasticity potential local and systemic application of cord blood stem cells may represent excellent candidates for cell-based therapeutic strategies in toxic liver injuries. It is already known that intraperitoneal administration of hematopoietic stem cells provides rapid liver homing in animal models of hepatic injury. We sought to assess the efficacy of a hematopoietic stem cell infusion to decrease the histologic damage and the mortality rate of animals previously damaged by allyl alcohol. MATERIAL AND METHODS: NOD/SCID mice were divided into two groups. (1) animals treated by intraperitoneal administration of allyl alcohol and (2) animals treated with allyl alcohol and 24 hours later with an intraperitoneal infusion of human cord blood cells. Flow cytometry, histology, immunohistochemistry, and RT-PCR were performed to monitor human cell engraftment by evidences of human hepatic markers. RESULTS: Human stem cells were able to transdifferentiate into hepatocytes, improve liver regeneration after damage, and reduce the mortality rate even when requiring qualitative and quantitative differences in the transdifferentiation processes. The mortality rate decreased from 70% to 20%, with a significant improvement in the histologic findings. CONCLUSION: We demonstrated that the infusion of hematopoietic stem cells into the liver in the early stage of damage might initiate endogenous hepatic tissue regeneration that oppose the injury inflicted by toxicants.
BACKGROUND: Liver regeneration is a heterogeneous phenomenon involving the proliferation of different cell lineages in response to injury. Under a strong positive selection pressure bone marrow derived stem cells may be involved in this process, by making a contribution to both parenchymal restoration and endothelial cell replacement. We investigate bone marrow stem cell migration to the liver in patients undergoing hepatectomy or with acute on chronic liver failure. METHODS: We enrolled 6 patients submitted to hepatectomy, 6 patients to cholecystectomy and 8 patients with acute decompensation of liver cirrhosis. Mobilization of CD34+ cells was evaluated by cytofluorimetry on peripheral blood samples at different time points; baseline, 1, 3, 7, 15 and 30 days after surgery and at admission, 1, 7 and discharge among patients with acute on chronic liver failure. 10 healthy subjects undergoing blood donation were also enrolled to evaluated the basal value of CD34+ cells. RESULTS: White blood cell counts remained in the normal range (4.1-9.8 x 10(9)/L) in all groups throughout the follow-up. In all patients of Groups 1, 2 and 3, circulating CD34+ failed to show statistically significant differences both as the absolute number and as the percentage at any time point compared to healthy controls. CONCLUSIONS: Bone marrow derived cell mobilization can not be detected after hepatectomy or during an acute decompensation on a cirrhotic liver. Under these circumstances liver regeneration can probably call upon mature hepatocytes and endogenous progenitor cells. The involvement of extrahepatic progenitors if any, is a rare and limited phenomenon.
BACKGROUND AND AIM: Tissue homeostasis and turnover require reserve stem proliferating cells. Several studies performed on immunodeficient animals have suggested a degree of plasticity by the hematopoietic stem cell compartment that may represent source for liver regeneration. We sought to explore the hepatic differentiation potential of hematopoietic stem cells from human cord blood, after toxic liver damage induced by allyl-alcohol in immunocompetent rats. MATERIALS AND METHODS: Wistar rats were divided into groups (A) allyl-alcohol intraperitoneal injection with hematopoietic stem cell intraperitoneal infusion at 1 day and sacrifice 3 days later; (B) stem cell injection and sacrifice 3 days later; (C) allyl-alcohol infusion and sacrifice 4 days later; and (D) sacrifice without any treatment. Livers, spleens, and bone marrows were analysed for human stem cells using flow-cytometry; livers were also tested by histology and immunohistochemistry to study the pattern of hepatic regeneration after damage and human stem cell conversion into hepatocyte-like cells, respectively. RESULTS: Flow-cytometry revealed selective recruitment of human hematopoietic stem cells by damaged livers (group A) compared with control group B. In addition, liver damage was reduced in animals treated with stem cells. Immunohistochemistry demonstrated that human stem cells could convert hepatic cells. CONCLUSIONS: Our study demonstrated that hematopoietic stem cells selectively recruited by injured livers can contribute to hepatic regeneration after acute toxic damage in immunocompetent recipients.
We evaluated the influence of prolonged weightlessness on the performance of three cosmonauts to bilateral symmetry detection in the course of a 15-day-long Russian-French mission CASSIOPEE 96 aboard the MIR station. We tested the influence of weightlessness on subjects' performance as a function of the retinal orientation of axis of symmetry. as a function of type of stimuli (closed versus multi-elements shapes) and as a function of visual field presentation (at fixation, left visual field. right visual field). The results indicate firstly a difference between presentation at fixation versus away of fixation. Away of fixation, no effect of microgravity on performance was shown. A hypothesis of hemispheric specialization for symmetry detection was not supported as well. At fixation, an effect of micro-gravity was shown and more interestingly, the effect was quite different as a function of type of shapes used. suggesting that symmetry detection is a multiple-stage process.
Complex objects are better recognized under a specific orientation. When presented upside down, a face, even very familiar, is recognized with greater difficulty than when presented upright ("Inversion effect"). Up to now it was not possible to decide whether the direction provided by gravity or the one provided by the retina and the body constitutes the spatial reference involved in this "Inversion effect". Three cosmonautes learned photographed faces on the ground and had to recognize them both on ground and on flight. Other photographed faces were learned in flight and where presented for recognition on flight. Results show that the Inversion effect is still present on flight for faces that have been learned on ground as well as for those learned on flight. Persistence of the inversion effect in 0-G shows that gravity is not involved as a spatial reference in recognition of faces. Learning and recognition performances of faces learned in flight were significantly lower than performances for faces learned on ground. A possible role of gravity in configural processing, but not in the Inversion effect, is suggested.
Five participants were tested on their ability to produce accurate and regular inter-response intervals in the 350 to 530 ms time range. Three of them were members of the French-Russian CASSIOPEE 96 spaceflight mission, and the other two were control subjects tested on the ground. During spaceflight, the target inter-response intervals were increasingly undershot and the timing became more variable (less regular). The increase in the timing variability was mostly attributable to the internal timekeeping processes rather than those involved in motor execution. The results are discussed with reference to the physiological mechanisms possibly underlying the timing of fast serial movements.
We describe a patient with acute lymphoblastic leukaemia who developed rhinocerebral zygomycosis during the aplastic phase induced by antineoplastic chemotherapy. The patient was treated with fluconazole intravenously (400 mg daily) for 30 days and underwent surgical debridement. As a result of this treatment a complete remission of the zygomycosis-associated symptoms was observed. The possibility of treating zygomycosis with fluconazole is discussed.
In 22 untreated patients with uncomplicated essential hypertension and in 10 normotensive subjects the plasma levels of thrombomodulin (TM), beta-thromboglobulin (beta-TG), D-dimer (DD), tissue-type plasminogen activator (t-PA) and plasminogen activator-inhibitor (PAI-1) were evaluated. The observed values show no significant difference in plasma TM, plasma and urine beta-TG concentration and plasma DD among hypertensive patients and controls. On the other hand, the levels of t-PA and PAI-1 in hypertensive patients were significantly higher than the values detected in normotensive control subjects. These data seem to indicate that, at initial stages of essential hypertension, the t-PA and PAI-1 levels increase.
Blood pressure (BP) is recursively variable during the day-night cycle because of a physiological circadian rhythm. The aim of this study is, therefore, to show how to construct the population reference limits (desms) for BP in its time varying 24-h pattern, starting from a small sample, in order to facilitate their use in a local context. The sample for standardization comprised 427 clinically healthy subjects (211 males and 216 females), ranging in age from 16 to 100 years, attending their routine activities. The procedure begins with the statistical biometry related to the sample, and proceeds with the computation of the BP desms related to (1) the time-qualified discrete values; (2) the parameters of circadian rhythm; (3) the daily pressure load. The pertaining rules are explained step by stop, allowing each one to prepare the proper local desms for BP 24-h pattern. These standards may be useful for validating the individual BP monitoring according to the upper limits of the circadian physiological variability in the diagnostic procedure for identifying hypertensive subjects.
Endoglin (CD105) is a component of the transforming growth factor-beta (TGF-beta) receptor (TGF-betaR) complex. Together with betaglycan, CD105 is considered as a TGF-betaR accessory molecule (also called TGF-betaRIII), but its functions in the receptor-ligand interactions are still poorly understood. A small subset of human CD34+ hematopoietic stem/progenitor cells that has phenotypic and functional features suggestive of very primitive hematopoietic cells expresses the CD105 antigen. CD34+/CD105+ cells recirculate in the peripheral blood of mobilized subjects and can be purified by immunomagnetic isolation strategies. The hematopoietic potential of these CD34+/CD105+ cells appears to be sustained by a combination of hematopoietic and non-hematopoietic cytokines, which comprises Flt3 ligand, erythropoietin, interleukin-15 and vascular endothelial growth factor. Endogenous TGF-beta1 is a crucial factor for the maintenance of CD34+/CD105+ immaturity acting through positive modulation of both CD105 and CD34 molecules in the absence of relevant effects on the cell cycle profile. CD105 is absent on very primitive CD34-/lineage-/CD45+ (CD34-Lin-) human hematopoietic cells isolated from cord blood. However, in vitro exposure of CD34-Lin- cells to exogenous TGF-beta1 causes the appearance of a discrete population of CD34+/CD105+ cells. Collectively, available data on CD105 expression and function in primitive hematopoiesis indicate that this molecule could cooperate with the dissociation of TGF-beta1 cell cycle effects from its other effects on cell survival and differentiation.
Peripheral blood progenitor cells (PBPC) represent an ideal source of stem cells for autologous transplantation because of technical advantages and more favourable engraftment kinetics. The reconstituion of a functional immune system occurs earlier in patients transplanted with cytokine-mobilized autologous PBPC compared with bone marrow; because of the greater T-cell content in PBPC products, donor-derived antigen-specific T-cells transferred with the graft might contribute to short-term immunity in transplant recipients. Despite a prompt reconstitution of B- and T-cell numbers, both B- and T-cell function are profoundly impaired for a prolonged period of time after PBPC infusion. The positive selection of CD34+ cells might provide effective tumor cell purging without compromising hematopoietic recovery in patients with acute leukemia, multiple myeloma, breast cancer and non-Hodgkin's lymphoma, whose autografts have been reported to contain malignant cells which might promote disease relapse. However, the incidence of viral infections in the early posttransplant period might be increased after CD34-selected compared with unmanipulated PBPC transplants, as a result of the lack of accessory and immune cells in the graft. The purpose of this review is to provide an update on immunological reconstitution after transplantation of autologous PBPC; in particular, emphasis will be placed on the mechanisms of immune dysfunction after the infusion of unmanipulated and CD34-selected autografts.