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Biomedical subjects

G F Stefanini

Publications and source records attributed to G F Stefanini.

At least 19 recordsLinked to original sources
PubMed1992

Serum markers of immune activation and liver allograft rejection.

We monitored the immune response after liver transplantation in 20 patients by measuring the serum levels of soluble interleukin-2 receptor (sIL-2R), soluble CD8 (sCD8), serum amyloid-A protein (SAA), and tumor necrosis factor-alpha (TNF-alpha). In six patients data were available to extend the follow-up period to one year. In all patients mean sIL-2R levels increased in the first month after liver transplantation, and subsequently decreased to values similar to pre-OLT ones, while SAA mean levels rose in the first week after OLT only in patients with rejection. sCD8 levels did not significantly rise after OLT, and TNF-alpha was undetectable in most cases. During episodes of rejection, rejector patients had significantly higher levels of sIL-2R, sCD8, and SAA than stable (without complications) patients. Conversely, no significant difference between rejectors and patients with other complications existed for any of the markers studied. These results diminish the importance of these serum markers of immune activation as laboratory tools in the differential diagnosis of acute rejection from other complications. However, sIL-2R, SAA, and sCD8 levels correlated with the histological grade of rejection and therefore can be utilized to monitor patients with an established diagnosis of acute rejection.

Biomarkers↗
PubMed1992

Phosphoinositide fatty acid composition of peripheral blood lymphocytes from aging humans.

The interaction of the T-cell receptor complex with the ligands is associated with early molecular events involved in the process of signal transduction implicating phosphoinositide breakdown. In elderly people, abnormalities in membrane signal transduction pathways are the basis of the immune deficiency associated with aging. Peripheral blood lymphocytes from aging humans and young subjects were stimulated with anti-CD3 monoclonal antibody and the phosphoinositide fractions were analyzed in order to determine the fatty acid composition in resting and stimulated conditions. In aging humans, in resting conditions, the all three phosphoinositide fractions appeared more saturated than the corresponding fractions in young subjects. Following anti-CD3 stimulation a decrease in arachidonic acid relative molar content was detected in both young and old subjects, but the arachidonic acid content in resting conditions greatly differed between the two groups, suggesting a different modulation of the microenvironment of the T-cell receptor complex in elderly people, so determining alterations in the early activation steps of lymphocytes.

Adult↗
PubMed1992

Oral disodium cromoglycate treatment on irritable bowel syndrome: an open study on 101 subjects with diarrheic type.

Several studies on the usefulness of oral disodium cromoglycate (DSCG) in the treatment of systemic adverse reaction to foods have been performed, with less attention to gastroenterological symptoms. In the present study, we selected 101 patients with diarrheic-type irritable bowel syndrome which improved after an elimination diet and worsened after a challenge with specific food(s). All patients were then tested for 48 commercial alimentary antigens by skin prick test (SPT) and underwent 8 wk of oral DSCG (500 mg three times a day), and the results were evaluated by means of a semiquantitative subjective and objective score. We observed an improvement of the symptoms in 67% of the 74 SPT-positive patients, whereas only 41% of the 27 SPT-negative patients showed a positive response to DSCG (p less than 0.05). These data confirm the protective role of DSCG in food-dependent diarrheic-type irritable bowel syndrome with food allergy features.

Administration, Oral↗
PubMed1991

[The usefulness of angiographic studies in the vascular complications of liver transplantation. The authors' own experience].

The authors report their experience with angiographic techniques in the diagnosis of vascular complications after liver transplantation. From 1986 to 1990, 78 patients were transplanted in our Hospital; of them, 8 underwent angiographic investigations for vascular complications. Angiography is very important when vascular complications are suspected, in the patients with a rise in cytolytic enzymes and in bilirubine levels, with hyperpyrexia, and with bioptic confirmation of no rejection. Duplex US is useful in the evaluation of portal canalization; if there are any doubts, angiography is performed also in the preoperative phase.

Adult↗
PubMed1991

Reversal of primary liver graft non-function using prostaglandins.

Primary graft non-function remains one of the most life-threatening problems after liver transplantation. Its etiology is still unclear. Liver retransplantation is the only therapeutic alternative to this problem. The PGE1 series of prostaglandins have recently been successfully used in the treatment of transplanted organ dysfunction. In this paper we describe a case of primary graft non-function successfully treated with continuous infusion of prostaglandin PGE1, and we briefly discuss the pathogenetic and therapeutic hypotheses.

Alprostadil↗
PubMed1990

Delta-6-desaturase activity of human liver microsomes from patients with different types of liver injury.

The delta-6-desaturase (D6D) activity was evaluated in microsomes from liver fragments of cholecystectomized subjects without any liver pathology and from explanted liver of patients affected by cirrhosis of different etiologies. We observed a significant decrease in D6D activity, evaluated by a radiochemical technique using 1-[14C]-linoleic acid as substrate, in cirrhotic patients with no correlation with the etiology of the cirrhosis. The D6D activity within the pathological group was quite similar. No alteration in the 20:4/18:2 ratio obtained by gas chromatographic analysis of fatty acid methyl esters of microsomal membranes was found. Liver disease seems to be the main cause of the decreased enzyme activity independent of its etiology.

Adult↗
PubMed1989

Class I and class II HLA antigen expression by transitional cell carcinoma of the bladder: correlation with T-cell infiltration and BCG treatment.

HLA class I and II glycoproteins from transitional cell carcinoma (TCC) and from perineoplastic and healthy vesical mucosa were characterized together with infiltrating cells by means of immunochemistry using specific monoclonal antibodies on frozen sections obtained during resection or radical cystectomy. Specimens were taken from 11 patients with TCC and five with healthy bladder mucosa. Four patients with TCC and four with healthy mucosa had been previously treated with a course of intravesical bacillus Calmette-Guerin (BCG). Ten out of 11 TCC samples expressed class I glycoproteins with a membrane pattern (diffuse in seven, focal in three) as normal epithelial cells from either controls or perineoplastic bladder. Interestingly, eight out of 11 TCC samples expressed class II antigens on their membrane that were also present in six cases in the perineoplastic tissue while the epithelial cells from four out of five normal bladders were completely negative. The epithelial display of class II antigens in the non-neoplastic areas and in the normal bladder correlates (p less than 0.001) with the degree of cellular infiltrate while such a relationship was not found between the HLA II expression of neoplastic cells and the infiltrate. BCG treatment was associated with a higher amount of inflammatory cells, prevalently T "activated" cells (CD5+,DR+), with a CD4/CD8 ratio always greater than 1. In the light of the role played by HLA glycoproteins in immune mechanisms, these results could help explain the positive action of BCG and the relative immunosensitivity of TCC.

Aged↗
PubMed1989

In vivo effect of chronic ethanol abuse on membrane alpha 1-glycoprotein of lymphocytes and immune response to various stimulating agents.

Data on the immune status of chronic alcoholic patients are rather conflicting probably due to the interference of liver disease and/or malnutrition on immune function. In order to avoid this kind of interference, peripheral lymphocytes from 12 chronic alcoholic patients in good nutritional status and without heavy liver damage and 15 healthy controls were examined in this study. Lymphocyte functional activity was evaluated by means of response to phytohemagglutinin, calcium ionophore A 23187, and autologous non-T-cells [autologous mixed lymphocyte reaction (AMLR)]. Phenotypical analysis was carried out by the indirect immunofluorescence technique using monoclonal antibodies specific to CD5 (mature T-lymphocytes), CD4 (helper/inducer T-lymphocytes), CD8 (suppressor/cytotoxic T-lymphocytes), glycoproteins, and an immunoglobulin fraction from rabbit directed to membrane alpha 1 acid glycoprotein (AGP) that is involved in T-cell activation process. Our results show significant impairment in AMLR while response to phytohemagglutinin, heterologous non-T-cells and carcinoma ionophore did not differ from controls. No differences were present in circulating T-lymphocytes expressing CD5, CD4, and CD8 on their membrane, whereas AGP-bearing lymphocytes were significantly lower in chronic alcoholics (14.4 +/- 8.6) than in controls (31.9 +/- 8.1; p less than 0.001). These results support the hypothesis of a direct action of alcohol on one of the pathways of lymphocyte activation and the role of the lymphocyte membrane AGP on the AMLR.

Adult↗
PubMed1989

Circulating LAK-1 cells and autologous mixed lymphocyte reaction in patients with hepatocellular carcinoma.

Autologous mixed lymphocyte reaction (AMLR) and phenotypical composition of circulating lymphocytes obtained from nine subjects with untreated hepatocellular carcinoma (HCC); three HCC patients locally treated by means of intraarterial chemoembolization; six subjects with gut-derived carcinoma (GDC); nine chronic active liver disease patients (CALD), and 14 normal controls have been evaluated, using monoclonal antibodies (MAB) against CD5, CD8, CD4 glycoproteins and anti-LAK-1 molecule, a novel 120-KD surface antigen that is present on the membrane of large granular lymphocytes, by means of classical indirect immunofluorescence technique. Autologous mixed lymphocyte reaction was significantly reduced in all patients, along with CD4-positive cells that are the responder cells in this reaction. A relative increase in the percentage of LAK cells was also observed in neoplastic patients with a normalization after local treatment of the HCC. In the light of promising results obtained by Rosenberg et al. by adoptive transfer of LAK cells activated with Interleukin-2 (IL2) in various cancers, our results support a similar therapeutic trial in HCC patients.

Adult↗
PubMed1989

Lymphocyte membrane alpha-1-acid glycoprotein: a cellular synthesis during lymphocyte activation.

Soluble alpha 1 acid-glycoprotein is considered an "acute phase protein" with an inhibitory effect on lymphocyte activity; it has recently been shown that a lymphocyte modulatory variant of alpha 1 acid-glycoprotein has a positive role on T cell activation. It is not clear whether the presence of this glycoprotein on lymphocyte membranes is due to an endogenous production or to a passive uptake of soluble alpha 1 acid-glycoprotein by its carbohydrate moiety. Our data show an increase of membrane alpha 1 acid-glycoprotein both in peripheral blood lymphocyte and T-enriched lymphocytes after phytohemagglutinin stimulation. Peripheral blood lymphocyte enzymatic treatment by neuraminidase does not affect alpha 1 acid-glycoprotein expression while pronase digestion induces a strong decrease of alpha 1 acid-glycoprotein positive lymphocytes and a resynthesis after phytohemagglutinin stimulation. Furthermore, the presence of alpha 1 acid-glycoprotein was prevalently, found on helper/inducer lymphocytes. These data support the hypothesis of a synthesis of alpha 1 acid-glycoprotein by T lymphocytes during their activation process.

Cell Membrane↗
PubMed1987

Reaction of T lymphocytes with anti-T3 induces translocation of C-kinase activity to the membrane and specific substrate phosphorylation.

Reaction of the T cell membrane with monoclonal antibodies to T3 can initiate cellular activation, and this is associated with increased intracellular Ca2+ and inositol-trisphosphate (IP3) release. We therefore studied the possible involvement of Ca2+/phospholipid-dependent kinase (C-kinase) in these phenomena. Quantitative assays of exogenous substrate phosphorylation in unstimulated cells showed Ca2+/phospholipid-dependent kinase activity in the cytosol, but no comparable activity in the particulate fractions corresponding to membrane and cytoskeleton material. At concentrations of soluble anti-T3 that partially activate T cells in the absence of macrophages, there was a 50 to 60% decrease in C-kinase activity in the cytosol, with a comparable increase in activity in the membrane fraction. A similar transfer of activity was also induced with the known C-kinase activator, 12-O-tetradecanoyl-phorbol-13-acetate, although redistribution was more rapid in onset, more complete, and more sustained. Redistribution of enzyme activity was additionally confirmed by qualitative assays of endogenous substrate phosphorylation. Labeling of intact cells followed by immunoprecipitation analysis with anti-T3 indicated signal-dependent phosphorylation of two components of the T3 complex and an unidentified 94,000 substrate that was resistant to reduction and alkylation. These findings are consistent with an important role for C-kinase in transduction of membrane events by the T3-Ti complex.

Antibodies↗
PubMed1987

A possible cytotoxicity inducer role of 5/9 positive lymphocytes infiltrating the liver in CAH patients.

The presence, in chronic active hepatitis (CAH) patients, of an inflammatory infiltrate basically composed of T lymphocytes suggested the hypothesis that these lymphocytes could play a role in the pathogenesis of the disease. The aim of this study has been to characterize, in a group of carefully selected CAH patients, the liver-infiltrating T lymphocyte, utilizing commercial monoclonal antibody (anti-Leu 1, anti-Leu 2a, anti-Leu 3a) and 5/9 monoclonal antibody that recognizes a further lymphocyte subset within T4 cells. Our data show that both T4 positive subpopulation and T8 positive subpopulation are represented in the infiltrate in the same ratio; furthermore the distribution of 5/9 positive lymphocytes is prevalent where the infiltrate is mainly composed of T8 positive lymphocytes. Moreover, there is a positive correlation between 5/9 positive cells in the liver and GPT and the patients with high percentages of infiltrating 5/9 positive lymphocytes show a low T4/T8 ratio with respect to patients with low percentages of 5/9 positive cells. These data support the hypothesis that 5/9 positive lymphocytes may present an inducer role on cytotoxic cells.

Adult↗
PubMed1987

Alpha 1-acid glycoprotein (alpha 1-AGP) on the membrane of human lymphocytes: possible involvement in cellular activation.

A glycoprotein termed alpha 1-acid glycoprotein (alpha 1-AGP) is a component of normal human serum; its concentration is often increased in several pathological disorders, including acute inflammation and cancer. Inhibitory effects of alpha 1-AGP on some in vitro T and B cell function assays have been reported but our recent data indicated that alpha 1-AGP is indeed a T cell mitogen at physiological concentrations. The present study was designed to investigate: (a) the relationship between this glycoprotein and two other glycoproteins of the T and B cell membrane, i.e. the T3 and Ia antigens; (b) the ability of lymphocytes to take up exogenous alpha 1-AGP; (c) the different expression of alpha 1-AGP on the T cell membrane upon different activation pathways, i.e., autologous non-T-cells (B cells and monocytes) phytohemagglutinin and anti-T3 monoclonal antibody (MAb) stimulations. The data reported herein show no competition at the membrane level between anti-alpha 1-AGP and anti-T3 or anti-Ia MAbs. In addition, (1) the lymphocytes were able to absorb alpha 1-AGP from the culture medium and (2) the expression of this glycoprotein was enhanced upon T cell stimulation (all three stimulants employed induced an increase of alpha 1-AGP positive T cells), thus suggesting a possible role of this glycoprotein in in vitro T cell activation.

Adult↗
PubMed1987

Expression of major histocompatibility complex class II antigens on bile duct epithelium in patients with hepatic graft-versus-host disease after bone marrow transplantation.

We studied the expression of major histocompatibility complex (MHC) class II antigens in liver biopsies taken from ten patients with clinical and biochemical evidence of liver damage after bone marrow transplantation. In all six patients who had histologically confirmed graft-versus-host disease, MHC class II antigens were detected on intrahepatic bile ducts. In four patients with no histological features of graft-versus-host disease, MHC class II antigens were not detected. In controls, a positive reaction for bile duct MHC class II antigens was only detected in the patients with primary biliary cirrhosis. Characterisation of the lymphocytes surrounding the bile ducts showed a prevalence of Leu 3+ cells in graft-versus-host disease and primary biliary cirrhosis. We propose that the aberrant expression of class II antigens on bile duct epithelium cells may play a role in the pathogenesis of graft-versus-host disease. A similar pattern in primary biliary cirrhosis may suggest a common pathogenetic mechanism.

Adult↗
PubMed1987

Alterations in helper-specific circulating T lymphocytes and in the autologous mixed lymphocyte reaction in chronic hepatitis B.

Defects in T lymphocyte subpopulations and in the functional characteristics of such cells have been thought to play a role in the evolution of chronic hepatitis B, but the precise nature of the alterations and their significance remains unresolved. We studied lymphocyte subsets in 27 patients with chronic hepatitis B utilizing standard monoclonal antibodies including Leu 1,2a,3a,7 and D1/12 (against the common determinant of the Dr molecule), as well as a newly described monoclonal antibody, "5/9," which is thought to characterize a unique subpopulation of T4 cells with specific helper/inducer function. These results were compared with those obtained using the autologous mixed lymphocyte reaction assay for the same patients in order to further delineate the lymphocyte alterations in chronic hepatitis B. A significant reduction in the mean number of Leu 3a (T4) positive cells was observed as well as a reduction in the number of 5/9 positive cells. These changes were most evident in those positive for HBeAg in serum. Reduction in Leu 3a cells was associated with a reduced autologous mixed lymphocyte reaction assay response, and was most marked in the HBeAg-positive individuals. These findings suggest that HBeAg-positive patients in whom active viral replication is occurring have a defect in T lymphocyte number and function, which may be due in part to reduced 5/9 positive cells. These alterations may be related to the persistence of virus in chronic active hepatitis B patients.

Antibodies, Monoclonal↗