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Biomedical subjects

M Mazzetti

Publications and source records attributed to M Mazzetti.

At least 37 records · Page 2Linked to original sources

[Effects of polyunsaturated phosphatidylcholine in alcoholic liver diseases].

The aim of this study is to assess "in vitro" the influence of polyunsaturated phosphatidylcholine on the erythrocyte membrane fluidity in alcoholics (greater than 180 g/die) and control subjects (less than 50 g/die), investigated by the evaluation of fluorescent polarization of DPH. In both groups a significant increase of membrane microviscosity was observed after incubation with 0.04 microM and 0.08 microM of PC compared to baseline values.

Adult↗

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↗

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↗

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↗

Post-injective quadriceps contracture.

After reviewing the literature, the authors report 19 patients affected with post-injective contracture of the quadriceps muscle observed by them between 1971 and 1983. Clinical evaluation, indications for surgery and the results of surgery are discussed.

Child↗

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↗

Reduced production of interleukin 2 and interferon-gamma and enhanced helper activity for IgG synthesis by cloned CD4+ T cells from patients with AIDS.

Purified T lymphocytes (E rosetting cells) isolated from peripheral blood (PB) of four patients with acquired immune deficiency syndrome (AIDS) were cloned under culture conditions (phytohemagglutinin plus interleukin 2) which allow clonal expansion of most T lymphocytes. A total number of 101 T cell clones (37 CD4+ and 64 CD8+) from PB of AIDS patients and of 188 T cell clones (115 CD4+ and 73 CD8+) from PB of four normal controls were obtained and tested for their helper function as well as for their capacity to release lymphokines. Unstimulated CD4+ TCC from patients with AIDS showed enhanced helper function for IgG synthesis in vitro in both autologous and normal allogeneic B cells in comparison to clonable CD4+ T cells of normal donors. Such activity was further potentiated by addition to the cell cultures of anti-CD3 monoclonal antibody. The majority of CD4+ T cell clones from AIDS patients showed a reduced ability to produce interleukin 2 and interferon-gamma in response to activation with phytohemagglutinin. However, most of them released greater amounts of soluble factor(s) able to promote B cell proliferation of anti-IgM-activated normal B cells and to induce the differentiation of normal B lymphocytes into IgG-secreting cells. These data demonstrate that most surviving CD4+ T cells in PB of patients with AIDS belong to a T cell subset producing B cell growth and differentiation factors, which may contribute to the B cell hyperactivation seen in AIDS patients.

Acquired Immunodeficiency Syndrome↗

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↗

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↗

Kallikrein and kininase activities excretion in newborns affected by jaundice.

In a homogeneous group of 30 newborns, aging between 10 hours--10 days, and affected by jaundice, urinary kallikrein and kininase activities were determined. The variable considered were: sex, time of life, weight and gestational age. Urinary samples were taken at the beginning and at the end of phototherapy.

Birth Weight↗

T lymphocyte subsets implicated in cytotoxicity in autologous hepatocytes in chronic active hepatitis patients with active viral replication.

We investigated inhibitory effect of various monoclonal antibodies on T-cell-mediated cytotoxicity against autologous hepatocytes in 24 patients with hepatitis B surface antigen/hepatitis B e antigen (HBsAg/HBeAg)-positive chronic active hepatitis. A significant reduction of cytotoxicity index occurred after preincubation of T lymphocytes with anti-Leu 7 (killer-natural killer cells), D1/12 (Ia-positive cells), 5/9 (restricted helper/inducer cells), and MLR4 ("activated" and radiosensitive helper cells) monoclonal antibodies (MAb). Anti-Leu 2a (cytotoxic/suppressor cells) and anti-Leu 3a (helper/inducer cells) MAb did not affect cytotoxic activity. This finding supports the hypothesis that the T cytotoxic reaction in this in vitro system is probably due to two mechanisms: first, spontaneous cell membrane cytotoxicity sustained by anti-Leu-7-positive lymphocytes; and second, specific cytotoxicity mediated by activated Ia-positive cells. We also found that the presence of helper/inducer cells (5/9 positive) appears to be a prerequisite for the cytotoxic reaction.

Adult↗

HTLV-III seropositivity in symptom-free Italian haemophiliacs. Correlation with consumption of commercial concentrate and abnormalities of T and B lymphocytes.

Various immunological parameters exploring both T- and B-cell functions were determined in a group of 74 symptom-free Italian haemophiliacs treated with commercial concentrate imported from the USA and were correlated with the presence in their serum of antibody to HTLV-III. There was a strong correlation between HTLV-III seropositivity and the amount of concentrate consumed. A significant correlation between HTLV-III seropositivity and T-cell alterations, such as T4/T8 ratio less than 1 and reduction in the absolute number of T4+ lymphocytes, or B-cell alterations such as hypergammaglobulinaemia and enhanced spontaneous IgG synthesis in vitro, was also observed.

Antibodies, Viral↗

Abnormalities of in vitro immunoglobulin production in apparently healthy haemophiliacs: relationship with alterations of T cell subsets and with HTLV-III seropositivity.

The pokeweed mitogen (PWM)-induced immunoglobulin (Ig) production by cultures of peripheral blood mononuclear cells (PBMC) was reduced in healthy haemophiliacs treated with commercial factor VIII (or IX) concentrate, whereas the spontaneous IgG synthesis in vitro was enhanced. PWM-induced Ig production was lower in those who had received greater amounts of concentrate, in those with inverted T4/T8 lymphocyte ratios and in those with antibody to HTLV-III. The spontaneous IgG production in vitro was higher in haemophiliacs who had received larger amounts of concentrate, in those with inverted T4/T8 ratio and in those with antibody anti-HTLV-III. However, some patients with normal T4/T8 ratio and some with HTLV-III antibody also had raised spontaneous IgG production.

Antibodies, Viral↗

Direct induction of human B-cell differentiation by recombinant interleukin-2.

Recombinant interleukin-2 (rIL-2) induced highly purified human tonsillar B cells to differentiate into immunoglobulin (Ig)-producing cells in vitro. The B-cell response was not due to rIL-2-contaminating substances, but reflected the activity of IL-2 itself, since it was inhibited by addition to the cultures of anti-TAC monoclonal antibody. The rIL-2-induced B-cell response was apparently not mediated by factors released by residual T cells present in B-cell suspensions at undetectable levels, since supernatants (SN) from unstimulated autologous T cells cultured at concentrations even much higher than those possibly contaminating B-cell suspensions did not induce any detectable Ig production. In addition, the Ig production by B cells cultured with SN prepared from high numbers of autologous T cells stimulated with rIL-2, as well as from allo-activated or mitogen-stimulated T cells, was of the same magnitude as the Ig production resulting from direct addition of rIL-2 concentrations comparable with those present in the supernatants. After centrifugation on Percoll density gradients, most of the tonsillar B cells responsive to rIL-2 were recovered in the lower density cell fraction containing a number of larger activated B cells. Moreover, B-cell enriched suspensions from peripheral blood (PB) (which usually contains a lower number of in vivo activated B cells than tonsil) showed poor or no response to rIL-2 alone, but displayed significant Ig production when rIL-2 was added to the cultures in the presence of Staphylococcus aureus Cowan I (SAC) bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗

Different reactivity of activated human B cells to B-cell growth factor and interleukin 2 in the costimulation assay with anti-IgM antibody and in the preactivation assay with Staphylococcus bacteria.

The two main assay systems which have been developed for the study of lymphokine-mediated human B-cell proliferation, i.e., the costimulation assay with anti-mu antibody and the preactivation assay with Staphylococcus aureus Cowan I (SAC) bacteria, were compared. Purified interleukin 2 (IL-2), obtained by the recombinant DNA technology (r-IL-2), enhanced the proliferative response of anti-mu-stimulated human B cells in the costimulation assay with anti-mu antibody and maintained the B-cell proliferation induced by preactivation with SAC bacteria. Although the majority of T-cell clones, established from normal peripheral blood T lymphocytes, showed production of both IL-2 and B-cell growth factor (BCGF) following phytohemagglutinin (PHA)-stimulation, some T-cell clones were found whose supernatants (PHA-SN), apparently free of IL-2, manifested strong BCGF activity in the costimulation assay with anti-mu antibody. However, the same clonal, IL-2-free, T-cell SN displayed no BCGF activity in the preactivation assay with SAC bacteria. When B cells were activated for 3 days with anti-mu antibody, followed by the addition of r-IL-2 or clonal T-cell SN containing BCGF for an additional 3 days, r-IL-2 showed the ability to maintain B-cell proliferation, whereas clonal SN containing BCGF had virtually no effect. These data indicate that the costimulation assay with anti-mu antibody explores the reactivity of normal human B cells to both BCGF and IL-2, whereas the preactivation assay with SAC bacteria, due to a shorter reactivity to BCGF of activated human B cells, essentially represents a probe for the study of IL-2-promoted B-cell proliferation.

Antibodies, Anti-Idiotypic↗

Synergy of B cell growth factor and interleukin 2 in the proliferation of activated human B cells.

The activity of purified interleukin 2 (IL2), obtained by the recombinant DNA technology, on the proliferative response of human B cells stimulated with low concentrations of anti-mu antibody was investigated. Recombinant IL2 was capable of augmenting the proliferative response of anti-mu-activated B cells and the T cell activation (Tac) antigen was expressed on a substantial proportion of normal B cells stimulated with anti-mu antibody. However, crude supernatants from protein A-stimulated peripheral blood mononuclear cells, which were found to possess both IL2 and B cell growth factor (BCGF) activities, maintained the ability to promote proliferation of anti-mu-activated B cells after depletion of IL2. In addition, supernatants from some T cell clones, apparently free of IL2 activity, displayed strong BCGF activity in the co-stimulation assay with anti-mu antibody. This BCGF activity was found in 25 kDa fractions by gel filtration and it was unaffected by addition to the cultures of anti-Tac antibody, which consistently inhibited the B cell proliferative response promoted by recombinant IL2. The proliferative response of anti-mu-activated B cells to clonal, IL2-free supernatants containing BCGF and recombinant IL2 present together from the beginning of culture was close to the sum of responses to the two stimulants, separately. In addition, the presence of clonal supernatant containing BCGF from the beginning of culture had a synergistic effect in the response of activated B cells to the subsequent addition of IL2, whereas the initial presence of IL2 had no such an effect on the reactivity of anti-mu-stimulated B cells to the late addition of clonal supernatant containing BCGF. The synergistic effect of BCGF in the IL2-promoted B cell proliferation was probably the result of the recruitment of a greater number of IL2-reactive B cells. In fact, the number of Tac-positive cells was significantly higher in 36-h cultures established in the presence of anti-mu antibody plus clonal supernatant containing BCGF than in cultures stimulated with anti-mu antibody alone. Taken together, these data indicate that anti-mu antibody promotes the expression by normal human B cells of distinct receptors for IL2 and a BCGF distinct from IL2. They also suggest that BCGF can exert a synergistic effect in the IL2-promoted proliferation of activated B cells.

Antibodies, Anti-Idiotypic↗

Long term results in Osgood-Schlatters disease.

The authors were able to establish a relationship between high patella (alta) and Osgood-Schlatter's disease. In a long-term study this was found in 38% of cases. There was also evidence of abnormalities of femoro-patellar relationship in 57% of cases, although only 14% of these had symptoms at the time of follow-up. Two alternative hypotheses on the pathogenesis of the disease are put forward, depending on whether the radiographic changes observed at follow-up were of a pre-existing constitutional type, or the direct result of the disease. This question can be resolved if in future cases a precise radiographic examination is carried out on both knees at the onset of the disease, using the exact technique described so that the relevant parameters can be determined.

Adult↗