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Biomedical subjects

P E Manconi

Publications and source records attributed to P E Manconi.

At least 19 recordsLinked to original sources

Properties of benzodiazepine binding sites in peripheral blood lymphocytes.

Benzodiazepine (BDZ) binding sites were studied by using 3H-diazepam and 3H-Ro 5-4864 in intact lymphocytes from peripheral blood (PBL), in comparison to kidney and cerebellum. Experiments with 3H-diazepam performed at equilibrium and measuring kinetics revealed that BDZ binding sites are indeed present in rat PBL. The binding is saturable (Bmax 557 fmoles/10(6) cells), with high affinity (KD = 9.3 nM) and reversible. Specific binding sites are also observed by saturation experiments with 3H-Ro 5-4864 (Bmax 175 fmoles/10(6) cells, KD 2.2 nM). In addition, analysis of saturation isotherms obtained with 3H-diazepam indicates that BDZ binding sites are also present in human PBL. Scatchard plot of binding isotherms revealed an apparent single population of sites in all cases. The pharmacological characterization of BDZ binding sites in PBL, as compared with those of kidney and cerebellum, showed that these sites belong to the so-called "peripheral type."

Animals

Human immunodeficiency virus infection in multi-transfused patients with thalassaemia major.

We investigated the incidence, clinical and immunological characteristics of human immuno-deficiency virus (HIV) infection in a group of multi-transfused patients with thalassaemia major who were exposed to transfusion-associated HIV infection. Seropositivity to HIV by Western blot and immunofluorescence analysis was detected in 26 out of 590 patients. At a follow up 21-40 months later, none of these seropositive patients had developed acquired immuno-deficiency syndrome (AIDS), and six manifested the AIDS related complex (ARC). ARC was unusually mild and consisted of moderate laterocervical and submandibular lymph node enlargement associated with hypergammaglobulinaemia and a reduced CD4/CD8 ratio resulting from the decreased number of CD4 lymphocytes. These findings suggest that multi-transfused patients with thalassaemia major are relatively resistant to the development of severe manifestations of HIV infection, presumably because their immune status is relatively better preserved than that of other infected populations. Longer follow up is, however, necessary to determine whether the incidence of AIDS will be lower in this population or whether overt AIDS merely takes longer to develop.

AIDS-Related Complex

Antigenic and cytochemical characterization of cells adhering to intrauterine contraceptive devices.

Eighteen copper intrauterine devices (IUDs), removed after 25 months of use, were examined to evaluate cells adhering to them (IAC). By means of monoclonal antibodies, the antigenic phenotype of IAC was studied, along with some IAC cytochemical properties. Sixty percent of IAC were identified as granulocytes based on morphological, cytochemical, and antigenic characteristics. A small proportion of IAC were shaped like large foreign-body macrophages, with multiple picnotic nuclei, and diffused alpha naphthyl acetate esterase (ANAE) activity. Some IAC identified as macrophages from a morphological view point also showed dipeptidyl-diaminopeptidase IV (DAPIV) reactivity, previously described only in T-helper lymphocytes. Most IAC identified as macrophages reacted with the monoclonal antibodies OKM1 and HLA-DR, and showed ANAE activity in the form of small multiple granules. The hypothesis that IUD-adhering macrophages with an ANAE+, DAPIV+, OKM1+, and HLA-DR+ phenotype could play a role in the inactivation of spermatozoa can be proposed.

Antibodies, Monoclonal

Influence of dehydroepiandrosterone on G-6-PD activity and 3H-thymidine uptake of human lymphocytes in vitro.

Dehydroepiandrosterone (DHEA) was found to inhibit experimental cancer development in mouse and rat lung, colon and mammary gland. Since DHEA is a potent inhibitor of mammalian G-6-PD, the hypothesis that the compound could inhibit cell proliferation through an inhibition of the pentose phosphate pathway has been formulated. We studied the effects of DHEA on the proliferation in vitro of human lymphocytes induced by several mitogens (PHA, ConA and PWM), measuring 3H-thymidine uptake. DHEA inhibited 3H-thymidine uptake of mitogen-stimulated cells from both G-6-PD+ and G-6-PD- (mediterranean type deficiency) individuals in a dose-dependent and reversible fashion. The inhibitory effect was found even if DHEA was added to cells in the last hours of culture, simultaneously with the addition of 3H-thymidine. These data suggest that the inhibition of thymidine uptake induced by DHEA on human lymphocytes probably does not depend on the inhibition of G-6-PD.

Cells, Cultured

Demonstration of antibodies to human T-lymphotropic retrovirus type III in lymphoadenopathy syndrome patients and in individuals at risk for acquired immune deficiency syndrome (AIDS) in Italy.

An epidemiologic survey of the distribution of lymphoadenopathy syndrome in six Italian cities and its correlation with human T-lymphotropic retrovirus III (HTLV-III) is reported. Serum samples of nine patients with acquired immune deficiency syndrome (AIDS) were tested, 180 from patients with lymphoadenopathy and 349 from individuals belonging to groups such as homosexuals, drug addicts, hemophiliacs, and polytransfused considered at increased risk for AIDS. Prevalence of HTLV-III antibodies was 78% in AIDS patients and 61% in 180 patients with lymphoadenopathy syndrome (variation among drug abusers by city from 51% in Cagliari to 87% in Rome). The percentage of positive sera in individuals at risk for AIDS or lymphoadenopathy ranged from 0% in polytransfused to 8.5% in homosexuals, 14% in drug addicts, and 19.5% in hemophiliacs. No positive sera were found among 660 healthy individuals including relatives of patients with AIDS or lymphoadenopathy or in 342 patients suffering from immunologic or infectious diseases. These results strongly suggest that HTLV-III is the causative agent of AIDS and lymphoadenopathy. Since none of the healthy subjects were positive while a substantial percentage of people at risk for AIDS showed antibodies to HTLV-III, it may be presumed that this infection is also prevalent in the Italian population group in which AIDS and lymphoadenopathy are most likely to develop.

Acquired Immunodeficiency Syndrome

The banding pattern produced by restriction endonucleases in mouse chromosomes.

The metaphase chromosomes of mouse have been treated with the restriction endonucleases Alu I, Mbo I, Hae III and Eco RII and subsequently stained with the DNA-specific dye Ethidium bromide. A striking correspondence between previous biochemical findings and our cytological results has been noticed with Alu I, Mbo I and Hae III, which were capable of digesting all but the DNA localized at the centric constitutive heterochromatic areas. Digestion with Eco RII, on the contrary, resulted in cytological data which apparently did not fit in with the biochemical results previously obtained by digesting the DNA of this species with the same enzyme. It is postulated that factors such as chromatin organization, in addition to DNA base sequence, can determine the results we report.

Animals

Lymph node immunohistology in intravenous drug abusers with persistent generalized lymphadenopathy.

Lymph node biopsy specimens from 16 intravenous drug abusers with persistent generalized lymphadenopathy were evaluated by immunohistochemical methods using a panel of antisera to detect different cell populations. The 11 cases that we tested on cryostat sections showed an increased number of Leu-2a-positive cells (cytotoxic-suppressor phenotype) in the follicular centers and a significantly reduced helper-to-suppressor T-cell mean ratio when compared with control tissues. In these 11 patients the peripheral helper-suppressor ratio was at the lower normal limit or inverted. Ten cases tested for anti-human T-cell lymphotropic virus type III antibodies were positive. In all 16 cases, immunohistology of paraffin-embedded sections demonstrated a polyclonal B population; 12 of 15 patients tested had polyclonal hypergammaglobulinemia, mostly IgG. The mixed-cell population of the lymph node sinuses was composed mostly of Leu-M1-positive and lysozyme-positive cells and, to a lesser extent, by alpha 1-antichymotrypsin-positive and S100 protein-positive cells. It seems that many of the immunologic dysfunctions found in these patients appear to be reflected in a fairly repetitive immunohistologic pattern.

Acquired Immunodeficiency Syndrome

Alpha-naphthyl acetate esterase activity in human lymphocytes: distribution in lymphocyte subpopulations and in mitogen-activated cells.

The cytochemical demonstration of nonspecific alpha-naphthyl acetate esterase (ANAE) activity in human peripheral blood mononuclear cells was studied. Different staining patterns were found, allowing differentiation of mononuclear cells into macrophages (strong granular cytoplasmic activity), B lymphocytes (negative reaction), Tgamma lymphocytes, i.e. bearing IgG Fc receptors (granular scattered reaction), and T non-gamma lymphocytes, i.e. devoid of IgG Fc receptors (single cytoplasmic ANAE spot). During the early phases of phytohaemagglutinin (PHA)- and concanavalin A (Con A)-induced activation, the reactivity of most lymphocytes became granular and scattered, similar to that found in Tgamma cells. Blast cells generating in successive phases appeared devoid of detectable enzymatic activity. The hypothesis is put forth that T cells showing granular, scattered reactivity represent a population of activated cells and that the redistribution of enzymatic activity could represent a preliminary step leading to secretion (lymphokine-like?) of enzyme from cytoplasm in the course of cell activation.

B-Lymphocytes

Surface markers on lymphocytes from human cerebrospinal fluid. Predominance of T lymphocytes bearing receptors for the Fc segment of IgG.

Surface markers of cerebrospinal fluid (CSF) cells have been studied in comparison with those of peripheral blood lymphocytes. The great majority (about 95%) of CSF cells bear surface markers of thymus-dependent lymphocytes (E rosettes with uncoated sheep red blood cells), while being devoid of bone-marrow derived cell markers (EAC rosettes with complement-coated red blood cells). In contrast with lymphocytes from peripheral blood, CSF cells form predominantly 'early' and 'sphere'-shaped E rosettes, and bear receptors for the complement-fixing segment of immunoglobulins G. Treatment with concentrated CSF does not affect rosette forming ability of peripheral blood lymphocytes.

Cerebrospinal Fluid

Subpopulations of T lymphocytes in human extravascular fluids.

Surface markers of lymphocytes from various human extravascular fluids (cerebrospinal fluid, aqueous humour, colostrum, breast and ovary cyst fluids, peritoneal and pleural transudates) are compared with those of lymphocytes from peripheral blood. Significantly higher percentages of T cells are found in all extravascular fluids: the great majority of extravascular T lymphocytes show high E rosette-forming ability and bear IgG Fc receptors (T Fc+ cells). Functional implications of the shown high predominance of T Fc+ cells in extravascular fluids are discussed on the basis of presently available information on the immunological role of such cells (cytotoxic? suppressor? amplifier?).

Antigens

T lymphocytes bearing receptors for Fc of IgG in guinea pig peritoneal fluid. A model for human extrahaematic fluids.

Surface markers of lymphocytes from peritoneal fluid of the guinea pig are studied and compared with those of lymphocytes from thymus, peripheral blood and spleen. The great majority of peritoneal lymphocytes form rosettes with rabbit red cells and bear receptors for Fc of IgG (T Fc+ cells). Lymphocytes with these characteristics are poorly represented in blood, thymus and spleen. Guinea pig peritoneal lymphocytes can be compared, as far as surface markers are concerned, with lymphocytes from human cerebrospinal fluid and transudates.

Animals