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Biomedical subjects

F Mariani

Publications and source records attributed to F Mariani.

At least 37 records · Page 2Linked to original sources

Functional inactivation in the whole population of human V gamma 9/V delta 2 T lymphocytes induced by a nonpeptidic antagonist.

Nonpeptidic compounds stimulate human T cells bearing the TCR-gamma delta in the absence of major histocompatibility complex restriction. We report that one of these ligands, 2,3-diphosphoglyceric acid (DPG), which induces expansion of V gamma 9/V delta T cells ex vivo, antagonizes the same cell population after repetitive activation. Stimulation with DPG results in partial early protein tyrosine phosphorylation and a prolonged, but reversible, state of unresponsiveness to agonist ligands in V gamma 9/V delta 2, but not in other T cells. These findings show that TCR antagonism is a general phenomenon of T cells. However, in contrast to the clonal specificity of altered peptides antagonizing alpha beta T cells, all the tested V gamma 9/V delta 2 polyclonal cell lines and clones become unresponsive, a fact that may be relevant for the regulation of their response in vivo.

2,3-Diphosphoglycerate↗

Apoptosis of human monocytes/macrophages in Mycobacterium tuberculosis infection.

Tuberculosis (TB) is still a major health problem, both as a single disease entity and as a cofactor in AIDS. The interaction between macrophage and Mycobacterium tuberculosis (MTB) is a critical step in the establishment of an early chronic infection. This study analyses the capacity of MTB to induce apoptosis in cells obtained by broncho-alveolar lavage (BAL) from patients with reactive pulmonary tuberculosis and from AIDS patients with disseminated pulmonary tuberculosis. Apoptosis was increased three-fold in BAL cells obtained from patients with pulmonary tuberculosis and even more markedly in alveolar macrophages of MTB-infected AIDS patients, compared with controls. Apoptosis was analysed and characterized by propidium iodide (PI) incorporation, terminal deoxy transferase (TDT)-mediated dUTP-biotin nick end labelling (TUNEL), and tissue transglutaminase (tTG) expression. The MTB-macrophage interaction was also investigated in vitro by infecting monocyte-derived macrophages (MDM) with MTB (virulent strain H37Rv). The induction of apoptosis by MTB required viable bacteria, was dose-dependent, and was restricted to H37Rv. Infection with either Mycobacterium avium complex (MAC) or HIV-1 and treatment with heat-killed MTB failed to induce apoptosis.

AIDS-Related Opportunistic Infections↗

Infection of human monocytes with Mycobacterium tuberculosis enhances human immunodeficiency virus type 1 replication and transmission to T cells.

Mycobacterium tuberculosis and human immunodeficiency virus type 1 (HIV-1) are virulent intracellular pathogens that invade and multiply within macrophages. The effect of M. tuberculosis on HIV-1 infection and replication was analyzed in vitro using human monocyte-derived macrophages (MDM) isolated from peripheral blood mononuclear cells by countercurrent centrifugal elutriation. Preinfection of MDM with M. tuberculosis followed by HIV-1 infection resulted in an increase in p24 release, reverse transcriptase activity, and infective virus production. In contrast, no increase in HIV-1 production was observed when MDM were infected with Mycobacterium avium complex or heat-killed M. tuberculosis. Coinfected MDM were potent stimulators of T cell proliferation, while HIV-1-infected MDM failed to present exogenous tuberculin to T cells. Furthermore, coinfected MDM showed an increased capacity to transmit HIV-1 to activated T cells. These results suggest that M. tuberculosis infection can both up-regulate HIV-1 infection and replication within MDM and increase the efficiency of virus transmission from infected MDM to T cells.

Cells, Cultured↗

[Anti-c antibody neonatal hemolytic disease: a case report].

The authors present a case of neonatal hemolytic disease caused by incompatibility with the erythrocytic c antigen. The presence of this surface antigen may stimulate anti-c antibodies even in the presence of compatibility with factor D, the larger of the characters.

Antibodies↗

Analysis of the adoptive transfer of delayed hypersensitivity and T cell repertoire in severe combined immunodeficiency mice reconstituted with human lymphocytes.

The functional capacity of human T cells to passively transfer delayed hypersensitivity (DH) was analysed in severe combined immunodeficiency (SCID) mice. The tissue distribution of human peripheral blood lymphocytes (PBL) was analysed by 51chromium labelling 1 and 24 h after intravenous cell injection. Labelled PBL from purified protein derivative (PPD)-positive healthy individuals mainly localize in the spleen, liver and lungs, with no arrival in the peripheral lymphoid organs and at the site of antigen challenge (footpad). According to such defective distribution, human PPD-immune cells failed to passively transfer PPD-specific DH to SCID recipients when cells were injected either intravenously or intraperitoneally (systemic transfer). On the contrary, PPD-immune cells were able to transfer DH to PPD when injected directly into the footpad (local transfer). Both memory (CD45RA-) and naive (CD45RA+) enriched subsets were equally able to transfer local DH. The long-term reconstitution of the human immune system in SCID mice was analysed after intraperitoneal PBL transfer (hu-PBL-Scid) by phenotypic analysis, immunoglobulin level, and human DNA detection. Moreover, the reconstitution of the V beta T cell receptor (TCR) repertoire in SCID mice was analysed by anchored polymerase chain reaction (PCR) showing that all the 22 V beta families were expressed in the spleen of hu-PBL-SCID mice. Moreover, scanner analysis of Southern blotting revealed the selective expansion of distinct V beta families (V beta 3, V beta 6, V beta 8, V beta 13.1, V beta 14, V beta 17), suggesting that human lymphocytes could recognize specific antigens or superantigens in the SCID environment.

Animals↗

Epitope specificity, antibody-dependent cellular cytotoxicity, and neutralizing activity of antibodies to human immunodeficiency virus type 1 in autoimmune MRL/lpr mice.

The specificity and functional activity of antibodies to human immunodeficiency virus (HIV) in the sera of MRL/lpr mice were analyzed by peptide-ELISA, antibody-dependent cellular cytotoxicity, and virus neutralization. The specificity of the antibodies in the sera of autoimmune MRL/lpr mice was similar to that of HIV-infected persons; the mouse sera specifically recognized the V3 loop of gp120 and immunodominant regions of gp41 and p24. Moreover, such binding was inhibited both by human HIV-positive sera and by soluble peptides in competition experiments. MRL/lpr sera displayed anti-HIV antibody-dependent cellular cytotoxicity using human peripheral blood lymphocytes as effector cells and HIV-infected H9 cells. Furthermore, the fact that MRL/lpr sera neutralized in vitro infectious HIV (both strains IIIB and MN) suggests these antibodies recognize viral epitopes on the membrane of infected T cells.

Amino Acid Sequence↗

Characterization of an IS-like element from Mycobacterium tuberculosis.

A DNA sequence, present in members of the Mycobacterium tuberculosis complex, has been identified and characterized. The distribution of this DNA sequence among mycobacterial species was analysed by DNA hybridization and PCR experiments. As the sequence was detected only in bacteria belonging to the M. tuberculosis complex, it may be useful for the rapid discrimination of mycobacteria. Interestingly, the sequence has some characteristics of an insertion element (IS) and codes for a hypothetical protein with significant homologies to proteins encoded by several IS elements of other organisms, namely IS427 and IS869 from Agrobacterium tumefaciens, IS402 from Pseudomonas cepacia, Tn4811 from Streptomyces lividans and ISRm4 from Rhizobium meliloti. Together, these elements form a previously unrecognized family of transposable elements. This finding suggests the possibility of horizontal gene transfer between pathogenic mycobacteria and other organisms including Gram-negative plant-pathogenic bacteria.

Amino Acid Sequence↗

Clinical outcome and emotional-behavioural status after isolated coronary surgery.

In order to evaluate clinical and psychosocial results of isolated coronary artery by-pass graft (CABG) we studied 626 consecutive patients, mean age 61 +/- 8 years (86% men), in a follow-up (median: 58 months) with a complete questionnaire about cardiosurgical problems (post-operative vital status, angina relapse, infarction, heart failure, PTCA, redo, PM) and psychosocial variables (mood, irritableness, job satisfaction, hobby satisfaction, family relations, sexual activity, general well-being and work status). Global evaluation improvement of psychosocial variables was found in 71% of patients without cardiac events (group A) and 11% of patients with cardiac events (group B); worsening was found in 2% of group A and 1% of group B; no referred variations in 13% and 2% respectively (p < or = 0.05. Interests (in work, hobbies and sexual activities) demonstrate an improvement in 20% (group A) and 2% (group B); worsening in 12% (group A) and 4% (group B); no variations in 51% (group A) and 11% (group B) (p < or = 0.005). Patients reported a well-being evaluation improvement about 66% in the group returning to work without restriction, 13% in those with limitation, 6% no further working; worse or unchanged well-being evaluation was found in 9% of patients returning to work without restriction, 3% with limitation, 3% no further working (p < or = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The IgG subclass antibody response to an inhalant antigen (Dermatophagoides pteronyssinus) during the first year of life: evidence for early stimulation of the immune system following natural exposure.

This study investigates the early humoral immune response following natural exposure to an inhalant antigen (Dermatophagoides pteronyssinus) in 36 babies, from birth until 1 year of age. The total IgG and subclass 1 and 4 D. pteronyssinus-specific antibody levels were assayed in sera collected at 7 days, 3 and 12 months by ELISA. After an initial fall, due to the progressive loss of maternal antibodies, an IgG specific response to D. pteronyssinus was seen between 3 and 12 months. This was restricted to the IgG1 subclass when the values at 12 months were significantly higher than those detected at the third month (P less than 0.001, paired t test). No D. pteronyssinus-specific IgG4 antibody was detected in any subject at any of the time points tested. The present study demonstrates that inhalant as well as food antigens are able to stimulate the immune system during the first year of life and that the antibodies produced are of the IgG1 subclass.

Administration, Inhalation↗

Early immune responses to Dermatophagoides pteronyssinus and atopic predisposition.

Responses to the house dust mite during infancy may be important determinants of asthma in susceptible individuals. This study assessed early IgG subclass antibody responses to Dermatophagoides pteronyssinus in children of atopic parents. Sixteen atopic and 15 non-atopic children were selected from a birth cohort, and atopic status was established according to follow up over the first two years. IgG1 and IgG4 antibodies to D pteronyssinus were measured by enzyme linked immunosorbent assay at 7 days and 3, 6, 12, and 24 months. In all children D pteronyssinus IgG1 fell at 3 months (indicating maternal antibody loss), rose progressively to 12 months, and waned at 24 months. D pteronyssinus IgG4 was only detectable at 7 days. Children who were atopic by 2 years and therefore at greater risk of asthma, tended to have higher D pteronyssinus IgG1 at 6 and 12 months. These data suggest greater exposure or responsiveness to dust mite during infancy than in the second year.

Aging↗

Treatment of bowel injuries in war surgery.

Provided that the surgeon is familiar with small and large bowel surgery, primary resection and anastomosis of the bowel, as well as primary suture of the perforations, are safe and advantageous procedures in treating war related intestinal perforations, whereas the use of colostomosis should be restricted to selected cases.

Adolescent↗

Identification of a specific Mycobacterium tuberculosis protein able to activate T lymphocytes.

The recent advances in the field of immunology and molecular biology allow to consider not distant the identification of protective antigens to be used in new prophilactic and diagnostic tools. In our laboratory we have analysed a M. tuberculosis expression library by murine monoclonal antibodies, human sera and human T lymphocytes. We have identified a 35 Kd protein present only on the M. tuberculosis complex (M. tuberculosis, M. bovis, M. africanum). This 35 Kd protein is also detected, by immunohistological analysis, inside the alveolar macrophage of pulmonary tuberculosis patients. Both recombinant beta-galactosidase and MS2 polymerase-fused proteins have been produced and used to perform western blotting and T cell proliferation assay. As the cloned fragment contains an internal EcoRI restriction site, it was possible to identify two fragments of 1.7 and 2.2 kb respectively. Southern blot analysis showed that both the fragments hibridized with the genomic DNA from M. tuberculosis complex but not with the DNA from other mycobacterial isolates from 12 pulmonary tuberculous patients hibridized with the 1.7 kb fragment. The possible use of this insert for the molecular diagnosis of tuberculosis is under investigation.

Animals↗

[Inhibition by ketotifen of specific skin wheal reaction in atopic subjects].

In order to reconsider the ability of ketotifen (K) to inhibit the specific (allergen-induced) skin wheal reaction (SWR) and the correlated problems, 32 patients, all suffering from seasonal allergic rhinitis due to grass pollens, have been studied. K has been compared with sodium cromoglycate (SCG), which is not metabolized in man. SPT with grass pollen extracts before and after treatment have been performed in all patients, divided into two numerically equal groups treated with either drug at usual dosages for eight weeks. The specific SWR has been significantly inhibited by K, but not by SCG. The theoretical and practical meaning of this finding is discussed.

Adult↗

Diagnostic accuracy of sialic acid in the diagnosis of malignant ascites.

The authors evaluated the diagnostic accuracy of sialic acid and its lipid-bound fraction in ascites and compared these tests with others (fibronectin, cholesterol) recently claimed as valuable in the differential diagnosis of ascites. Fibronectin yielded the best diagnostic accuracy (85%) with no false-positive and 37% of false-negative (10/27). The authors also found higher concentration of sialic acid in malignant ascites than in nonmalignant ascites (P less than 0.001) and, taking 300 mg/l as the cutoff value, the false-positive rate was 10% (four of 40), the false-negative rate 30% (eight of 27), and the overall diagnostic accuracy 82%, comparable to that of the fibronectin. The authors conclude that both fibronectin and sialic acid determinations in ascites may be regarded as accurate markers of neoplastic involvement of the peritoneum, although no test is useful in the ascites with hepatocellular carcinoma and cirrhosis of the liver.

Ascites↗

Correlation of morphological variables in the coronary atherosclerotic plaque with clinical patterns of ischemic heart disease.

The frequency and severity of "morphological" variables (fibrosis, proteoglycan accumulation, atheroma, intimal vascularization, calcification, acute intimal hemorrhage, and both adventitial and intimal lymphoplasmacellular infiltrates) in atherosclerotic plaques were related to plaque type, percentage of lumen reduction, plaque length, and intimal and medial thickness in 3,640 coronary artery sections sampled at the site of maximal lumen reduction in 8 selected segments from 100 cases of acute myocardial infarct, 50 of chronic angina, 208 of unexpected sudden coronary death with or without prodromata, and from 97 normal subjects dying accidentally. Morphological variables were occasionally observed in 1,519 sections with no lumen reduction. They were found only in sections from ischemic patients. With increasing luminal stenosis and intimal thickness, progression of the coronary plaque seemed to start as a fibrous change followed by proteoglycan accumulation in the deeper portion of the fibrous intima. Proteoglycan deposits appeared as a recurrent phenomenon. In them, atheroma or calcification develop. Intimal hemorrhage was a less frequent variable. It was found mainly in a vessel supplying an infarcted area. Lymphoplasmacellular inflammation correlated mainly with proteoglycan accumulation and atheroma, both showing a parallel increase with increasing intimal thickness and lumen reduction. No correlation was found between plaque variables and sex, age, heart weight, and infarct size. Significant variations in the distribution of plaque variables were observed among hearts of patients in the ischemic groups and between them and controls. In particular, inflammatory reaction was significantly more frequent and severe in ischemic groups than in controls, independent of the degree of coronary stenosis. Coagulative myocytolysis (contraction band necrosis), found in the majority of ischemic patients, correlated with the inflammatory reaction in supplying vessels. A peculiar tropism of mononuclear cell infiltrates for adventitial nerve structures was found. As a result, we question whether this inflammation may trigger coronary spasm and/or coagulative myocytolysis ("active" plaque vs "inactive" plaque).

Arteries↗

Diagnostic accuracy of fibronectin in the differential diagnosis of ascites.

To evaluate the diagnostic accuracy of fibronectin levels in ascites to differentiate malignant from non-malignant ascites, the authors studied 30 patients with sterile uncomplicated ascites in chronic liver disease, 18 patients with malignant ascites and four patients with spontaneous bacterial peritonitis. Fibronectin concentration was significantly higher in malignant ascites than in sterile ascites (P less than 0.001). High values (greater than 85 mg/l) were found in four of six cases of hepatocellular carcinoma in liver cirrhosis with negative cytologic examination, and in six of seven peritoneal carcinomatoses. Low values (less than 85 mg/l) were found in four patients with liver metastases and in one patient with intrahepatic biliary duct carcinoma in cirrhosis. In four patients with infected ascites, the fibronectin level was low. Among all other parameters (total protein concentration, lactate dehydrogenase, gamma-glutamyl-transpeptidase, pH, amylase, triglycerides, leukocyte count, and cytologic examination), fibronectin yielded the best degree of discrimination (diagnostic accuracy, 79%).

Adult↗