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Biomedical subjects

G Ferrari

Publications and source records attributed to G Ferrari.

At least 145 records · Page 8Linked to original sources

Surgical treatment and prognostic variables of hepatocellular carcinoma in 122 cirrhotics.

A 10-year experience in surgical treatment of HCC in 122 cirrhotic patients has been reviewed in order to evaluate: perioperative mortality and morbidity, survival rates and prognostic variables by multiple-logistic analysis. Mortality rate declined from 7% in period 1983-88 to 2% in period 1989-92. Operative complications also decreased from 46% to 30%. The 3-year and 5-year overall survival rates were 42.6% and 23.3%. The 3-year and 5-year survival of patients who died only for HCC was 51.1% and 34.2% and the disease-free survival 30.6% and 19.1%. The good results of overall survival were vanished by the high rate of recurrence (19.1%). Multiple logistic regression analysis for the probability of mortality was significant for satellite nodules (RR 2.437), microvascular infiltration (RR 2.432), tumor size (RR 1.147); the model for the probability of recurrence was significant for microvascular infiltration (RR 2.290), satellite nodules (RR 2.280), lesions number (RR 2.216) and tumor size (RR 1.247).

Carcinoma, Hepatocellular↗

N-acetylcysteine (D- and L-stereoisomers) prevents apoptotic death of neuronal cells.

In the present study we tested whether N-acetyl-L-cysteine (LNAC) affects apoptotic death of neuronal cells caused by trophic factor deprivation. LNAC, an antioxidant, elevates intracellular levels of glutathione. We used serum-deprived PC12 cells, neuronally differentiated PC12 cells deprived of serum and NGF, and NGF-deprived neonatal sympathetic neurons. In each case LNAC prevents apoptotic DNA fragmentation and maintains long-term survival in the absence of other trophic support. Unlike NGF, LNAC does not induce or maintain neurite outgrowth or somatic hypertrophy. To rule out actions of LNAC metabolic derivatives, we assessed N-acetyl-D-cysteine (DNAC). DNAC also prevents death of PC12 cells and sympathetic neurons. However, other antioxidants were ineffective in this regard. Since it has been hypothesized that trophic factors prevent neuronal death by either preventing or coordinating cell cycle progression, we tested whether LNAC or DNAC treatment can affect cell cycle. We found that both (but not other antioxidants) suppress proliferation and DNA synthesis by PC12 cells and do so at concentrations similar to those at which they prevent apoptotic death. Although the abilities of LNAC and DNAC to rescue cells from apoptosis triggered by trophic factor deprivation could derive from their direct influences on cellular responsiveness to oxidative stress, our observations raise the possibility of a mechanism involving cell cycle regulation.

Acetylcysteine↗

[Gynecomastia in chronic renal insufficiency. Presentation of a clinical case].

Gynecomastia may occur in men with chronic renal failure, developing in the course of complex endocrine abnormalities. It is often associated with aberration in the hypothalamo-pituitary-testicular axis even producing a severe hypogonadism. A case of monolateral gynecomastia in a hemodialyzed young man, without other clinical and endocrine signs, is described.

Adult↗

Blood cell redistribution in the lung after administration of recombinant human granulocyte-macrophage colony-stimulating factor.

Granulocyte-macrophage colony-stimulating factor (GM-CSF), in addition to being a haematopoietic growth factor, has been shown to stimulate in vitro the production of interleukins 1, 6 and 8 (IL-1, IL-6 and IL-8), tumour necrosis factor-alpha (TNF-alpha) and GM-CSF by polymorphonuclear cells (PMNs), alveolar macrophages (AMs), fibroblasts and endothelial cells of the lung, and the growth and differentiation of resident alveolar macrophages. The aim of this study was to establish whether recombinant GM-CSF (rhGM-CSF), administered subcutaneously at a dose of 5 micrograms.kg-1 for 3 days in five patients with unresectable non-small cell lung cancer before starting chemotherapy, induces an increase in the alveolar cell count, and whether these cellular lung variations may be related to increases in the above-mentioned cytokines. In the bronchoalveolar lavage fluid (BALF) total cell count, polymorphonuclear cells, neutrophils, and alveolar macrophages increased significantly in comparison with the baseline, and the extent of variation of the BAL cell count was considerably greater than that of the circulating leucocytes. The mean levels of all the cytokines increased, but a significant difference with respect to the basal condition was observed only for IL-6 and IL-8. After rhGM-CSF treatment, significant correlations were found between neutrophil counts and the levels of IL-6 and IL-8. In conclusion, rhGM-CSF administration induces a cellular expansion in the lung, and the neutrophil increase appears to be related to increased levels of IL-8.

Aged↗

[Isolated oculomotor palsy disclosing multiple myeloma].

Two cases of oculomotor nerves involvement as uncommon initial manifestation of a parasellar extramedullary plasmacytoma are reported. The first patient presented with an isolated left VI cranial nerve palsy; the second one had an incomplete left III cranial nerve palsy. In both cases clinical investigation and computed tomography revealed an intracranial plasmacytoma associated with multiple myeloma. It is important to underline the difference between an intracranial extramedullary plasmacytoma and a plasmacytoma associated with multiple myeloma. In fact the absence of a general associated illness should show a most favourable course.

Abducens Nerve↗

Proliferative inhibition by dominant-negative Ras rescues naive and neuronally differentiated PC12 cells from apoptotic death.

We have used the nerve growth factor (NGF)-responsive PC12 cell line as a model to examine the role of cell cycle progression in apoptotic neuronal cell death triggered by withdrawal of trophic support. Because p21 Ras plays a key role in mitogenic signaling, we tested whether interference with the activity of this protein would affect cell cycle progression and thereby apoptotic death after trophic factor deprivation. For this purpose, we exploited PC12 cells transfected with an inducible form of dominant-inhibitory Ras. In contrast to non-transfected and uninduced cells, which continue to synthesize DNA when deprived of trophic support, PC12 cells induced to express dominant-inhibitory Ras showed little thymidine incorporation. When non-transfected and uninduced cells were deprived of trophic support, these underwent rapid apoptotic death that could be prevented by NGF. However, cells in which dominant-inhibitory Ras was induced and which were consequently quiescent did not die upon withdrawal of trophic support and showed long-term survival in the absence of NGF or other trophic factors. Moreover, induction of dominant-inhibitory Ras also rescued non-dividing, neuronally differentiated PC12 cells from death caused by NGF withdrawal. These findings suggest a relationship between proliferative capacity and neuronal apoptosis and raise the hypothesis that following withdrawal of trophic support, neurons undergo an unsuccessful and fatal attempt to re-enter the cell cycle.

Animals↗

An efficient Th2-type memory follows CD8+ lymphocyte-driven and eosinophil-mediated rejection of a spontaneous mouse mammary adenocarcinoma engineered to release IL-4.

A retroviral infection was used to introduce the cDNA coding for mouse IL-4 into the parental cells of a spontaneous adenocarcinoma of BALB/c mice (TS/A-pc). Four clones releasing between 5 to 40 U of IL-4 (10(5) cells) in 48 h culture were selected. The secretion of IL-4 does not affect their in vitro growth, whereas their ability to form tumor in vivo inversely correlates with the amount of IL-4 secreted. Although morphologic observation suggested that the rejection of clone D5.40 cells (releasing 40 U of IL-4) depends on eosinophil cytolysis, lymphocyte depletion experiments showed that this required CD8+ lymphocyte guidance. Mice that had rejected D5.40 cells were immune to a subsequent challenge with TS/A-pc. This memory rests on the interaction between noncytotoxic lymphocytes, eosinophils, and IgG1 and IgE anti-TS/A Abs. Comparison of these memory mechanisms with those elicited by IL-2 gene-transduced TS/A cells shows that the kind of cytokine released by the tumor cells determines the type of response. This Th2 memory seems to be more efficient in protecting against a subsequent challenge of TS/A-pc than the Th1-type memory elicited by IL-2 gene-transduced TS/A cells.

Adenocarcinoma↗

Peripheral blood lymphocytes as target cells of retroviral vector-mediated gene transfer.

Peripheral blood lymphocytes (PBLs) are key target cells for gene therapy of a number of inherited and acquired blood disorders. We have systematically compared four retroviral vectors, designed according to different strategies, for their efficiency in transfer and expression in human PBLs of the same reporter gene. The receptor gene used in the study codes for the human low-affinity nerve growth factor receptor (LNGFR), and is not expressed on the majority of human hematopoietic cells, thus allowing quantitative analysis of the transduced gene expression by immunofluorescence, with single cell resolution. Peripheral blood mononuclear cells (PBMCs), as well as human hematopoietic cell lines of myeloid and lymphoid origin, were transduced with the four vectors and analyzed for efficiency of gene transfer, integration and stability of vector proviruses, and LNGFR expression at both RNA and protein level. Fluorescence-activated cell sorter analysis of coexpression of LNGFR and lineage-specific cell surface markers was performed in transduced cell lines, PBLs, and T-cell clones to study gene expression on specific cell subpopulations. Although crucial differences were observed among different constructs, all retroviral vectors could transduce, under appropriate infection conditions, T-cell populations representative of the normal immune repertoire. Gene transfer and expression could be demonstrated also in circulating progenitors of mature T cells. Expression of the transduced gene was heterogeneous among cell populations infected with the different vectors, with optimal results obtained by two of the four constructs. Finally, we have devised a simple protocol based on vector-mediated gene transfer and positive immunoselection of the transduced cells that produces virtually 100% gene-modified cells. This may represent a crucial improvement in the way of designing efficacious protocols involving the use of gene-modified T lymphocytes in clinical studies.

Cell Line↗

Schwann cells transplanted in the lateral ventricles prevent the functional and anatomical effects of monocular deprivation in the rat.

We investigated whether the transplant of Schwann cells prevents the physiological and morphological effects of monocular deprivation in the rat. On the day of eye opening in rats (postnatal day 14), we transplanted Schwann cells in the lateral ventricles and sutured the eyelids of one eye. After 20-30 days, at the end of the critical period for the visual system development, we analyzed the functional properties of visual cortical neurons. Spontaneous discharge, orientation selectivity, and receptive field size of visual cortical neurons in transplanted animals were in the normal range. Transplantation of Schwann cells prevented the detrimental effects of monocular deprivation on ocular dominance and binocularity of cortical neurons. Visual acuity of the deprived eye estimated by visually evoked potentials was also normal. Schwann cells derived from adult animals were as effective as those derived from neonates. The effects of Schwann cells on monocular deprivation were dependent upon the number of cells present in the transplant so that 10(6) Schwann cells were sufficient to prevent the effect of monocular deprivation, whereas 10(5) and 3.3 x 10(5) Schwann cells were ineffective, and 6.3 x 10(5) cells gave variable results. Shrinkage of the deprived lateral geniculate neurons was prevented by a transplant of 10(6) cells. In rats transplanted with hybridoma cells producing an antibody that functionally blocks nerve growth factor (NGF), we found that the effect of cotransplanted Schwann cells on monocular deprivation was partly counteracted. We conclude that transplantation of Schwann cells prevents both functional and anatomical effects of monocular deprivation, presumably acting through the production of NGF. We propose that transplants of Schwann cells could be a promising technique for clinical applications.

Animals↗

Evidence for a stromal cell-dependent, self-renewing B cell population in lymphoid follicles of the ileal Peyer's patch of sheep.

Lymphoid follicles of the ileal Peyer's patch (PP) of young sheep function as the major source of B cells and a site of immunoglobulin (Ig) receptor diversification. However, extensive cell death in culture has restricted investigations of ileal PP follicular (iPf)B cell biology. We investigated the possibility that sustained iPfB cell proliferation may require an interaction with mesenchymal stromal cells (SC). Four SC lines, cloned from lymphoid follicles of the ileal PP, and various sheep and xenogeneic mesenchymal cells were used to characterize the nature of iPfB cell-SC interactions. A sustained proliferative response was unique to iPfB cells, required iPfB cell-SC contact, and SC membranes functioned as intact SC to either enhance or inhibit iPfB cell proliferative responses. The iPfB cell proliferation in SC co-cultures was accompanied by extensive cell death and a slow decline in viable cell number. Flow cytometric analysis confirmed that viable lymphocytes, present in SC co-cultures, were immature B cells that expressed surface IgM, with either lambda or kappa. Ig light chain, and that SC co-culture inhibited iPfB cell differentiation. Finally, addition of soluble anti-sheep Ig to iPfB cell-SC co-cultures did not inhibit SC-dependent iPfB cell proliferation or iPfB cell binding to SC. These data indicate that an interaction between specific SC membrane molecules and non-Ig molecules of iPfB cells either supported or inhibited a self-renewing proliferative response by immature (sIgMLo, BAQ44A-) iPfB cells. Finally, SC-dependent iPfB cell proliferation was independent of T cells and extrinsic antigen which further suggests that a functionally distinct B cell population resides in lymphoid follicles of the ileal PP.

Animals↗

Deep cerebral venous thrombosis and hereditary tissue plasminogen activator (t-PA) deficiency.

We describe a patient with defective tissue plasminogen activator (t-PA) release who developed internal cerebral vein thrombosis. She recovered completely and, as shown by MRI, favourable outcome was probably related to vascular recanalisation. Other members of the pedigree had a similar fibrinolytic deficiency without clinical manifestations. The use of oral contraceptives may have contributed to the patient's hypercoagulable state.

Adult↗

Acute radiculomyelitis after antitetanus vaccination.

Active or passive immunisation with vaccines or sera can cause lesions of immunomediated pathogenesis involving both the central (CNS) and the peripheral nervous system (PNS). Although very rare, the neurological complications described during antitetanus vaccinations almost exclusively affect the PNS, those affecting the CNS being even more rare. The authors report a case of transverse myelitis with a radicular component, which arose acutely following the administration of tetanus toxoid and had a partially favourable course.

Acute Disease↗

A desk-top computer model of the circulatory system for heart assistance simulation: effect of an LVAD on energetic relationships inside the left ventricle.

The study of the interaction between a pneumatic left ventricle assist device (LVAD), driven with different control strategies, and the cardiovascular system is the subject of this paper. It is performed by a modular numerical model of the cardiovascular system connected to a numerical model of the LVAD. The circulatory system is simulated by a lumped parameter numerical model. The ventricle is represented by a time-varying elastance model to reproduce the Starling law of the heart. The effect of the LVAD on the cardiovascular system is evaluated, on the left ventricle alone, by an open-loop circuit consisting of the models of the ventricle, the LVAD and the arterial tree. The analysis is performed in terms of energy variables (such as external work and oxygen consumption and cardiac mechanical efficiency versus control strategy. The LVAD is driven by different control strategies: a fixed heart rate (with different delays from the onset of the natural ventricle contraction) and a variable heart rate.

Cardiovascular Physiological Phenomena↗