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Biomedical subjects

A Amadori

Publications and source records attributed to A Amadori.

At least 19 recordsLinked to original sources
PubMed1995

A CD3+CD8+ T cell population lacking CD5 antigen expression is expanded in peripheral blood of human immunodeficiency virus-infected patients.

In this study we analyzed the behavior of a CD3+ T cell subpopulation lacking CD5 antigen expression in PBMC from HIV-1-infected patients. CD3+CD5- lymphocytes were greatly increased in peripheral blood of HIV-1+ patients, accounting for 20.6 +/- 9.9% of the total CD3+ cells, compared to seronegative individuals (5.5 +/- 3.2%). In both seropositive patients and controls, CD3+CD5- cells belonged to the CD8+ compartment; they were nonactivated, TCR alpha/beta+, naive lymphocytes, and in seronegative individuals preferentially expressed NK cell-associated markers, such as CD11b, CD16, CD56, and CD57. The phenotypic profile of this subset was slightly different in seropositive patients; while TCR expression and CD45RA/RO profile were comparable, CD11b and CD16 expression was lower compared to control figures, while CD56 expression was not changed, and CD57 expression was enhanced. Functional analysis of enriched CD3+CD8+CD5- cells showed an impaired ability to proliferate in response to mitogenic and antigenic stimuli; despite their NK-like phenotype, CD3+CD8+CD5- cells did not exert any NK cytotoxic activity, and only a lectin-dependent cytotoxic potential could be evidenced in this population. These results describe a novel alteration in the lymphocytes phenotypic profile during HIV-1 infection, involving a "transitional" population, which shares some properties of the T and of the NK cell lineage.

Biomarkers↗
PubMed1995

Dominance of a single Epstein-Barr virus strain in SCID-mouse tumors induced by injection of peripheral blood mononuclear cells from healthy human donors.

Severe Combined Immune Deficiency mouse tumors, induced by inoculating peripheral blood mononuclear cells from 11 healthy human donors (hu-PBMC-SCID tumors), were used to analyse Epstein-Barr virus (EBV) type and strain variations. PCR analysis of EBNA 2- and EBNA 3C-specific sequences showed that EBV type A was present in SCID-mouse tumors induced by PBMC from all donors but one, while, using amplimers for a highly polymorphic region within the latent membrane protein (LMP) coding sequence, 5 different strains could be detected among the samples examined. The same LMP fragment was present in different tumors arising in the same animal, as well as in different mice injected with PBMC from any donor. Compared to B95.8 and AG876 prototype viruses, sequence analysis of LMP variants disclosed a higher homology to the latter, with 33 bp additional repetitions and a few point mutations in specific sites. This study confirms and extends previous data on the presence of a single EBV type and strain in the peripheral blood of most normal healthy subjects using the SCID-mouse system.

Amino Acid Sequence↗
PubMed1995

Genetic control of the CD4/CD8 T-cell ratio in humans.

We studied the genetic pattern of inheritance of the ratio between circulating CD4+ and CD8+ T lymphocytes in a population of healthy donors. The distribution of the CD4/CD8 ratio in males and females was significantly different and was significantly affected by age. In 46 randomly selected families, the parental CD4/CD8 ratio significantly influenced the ratio in offspring. Complex segregation analysis of the data rejected the non-genetic hypothesis; among the genetic models tested, a major recessive gene with a polygenic component and random environmental effects was the most parsimonious model. These findings indicate that the ratio of CD4+ and CD8+ T cells is genetically controlled in humans.

Adult↗
PubMed1994

Lymphoproliferative disease in human peripheral-blood-mononuclear-cell- injected scid mice. II. Role of host and donor factors in tumor generation.

Intraperitoneal injection of lymphoid cells from EBV+ donors into SCID mice might provide a useful tool for studying the pathways of B-cell lymphomagenesis in man. Since previous studies showed that donor T cells greatly favor B-cell proliferation and tumor generation in this model, we addressed the host and donor factors involved in limiting or promoting lymphoma development. The number of EBV-infected B-cell precursors was crucial, since purified B lymphocytes, which alone were unable to generate tumors, underwent expansion and established tumor masses when the animals were inoculated with an EBV-containing supernatant. Host factors were critical in limiting tumor development; in vivo NK-cell removal allowed purified B cells to expand and proceed to tumors in the absence of T lymphocytes, whereas potentiation of mouse NK-cell activity prevented tumor generation in PBMC- and LCL-injected animals. The T-cell-derived factors that favor lymphomagenesis could not be identified; IL-2, IL-4, IL-6, and soluble CD23 were not able to promote B-cell expansion, and treatment of PBMC-injected mice with the relevant anti-cytokine anti-sera did not counteract lymphoma development. These experiments also showed that IL-6 plays a minor role, if any, in B-cell lymphoproliferation in this model. Our data indicate that reconstitution of SCID mice with PBMC from EBV+ donors may constitute a useful model for determining the events involved in lymphomagenesis in humans, provided that strict control of all the experimental variables is guaranteed.

Animals↗
PubMed1994

Epidermal growth factor receptor expression and endometrial cancer histotypes.

Epidermal growth factor receptor (EGF-R) has been implicated in the growth of endometrial cancer. In the present study, immunostaining of EGF-R was investigated in different endometrial cancer histotypes. For this purpose 34 surgical samples of primary endometrial carcinoma were studied using monoclonal anti-EGF-R antibody. The endometrial carcinomas were classified according to the International Society of Gynaecological Pathology (I.S.G.P.). EGF-R expression was observed in: 1 of 5 classical endometrioid adenocarcinomas (AE), in 8 of 9 endometrial adenocarcinomas with benign squamous metaplasia (AA), and in 3 of 14 adenosquamous adenocarcinomas (AS). In mucinous (M) and serous papillary adenocarcinoma (SP) EGF-R immunostaining was not observed. The EGF-R positivity was observed in endometrial cancer with squamous (SQ) differentiation, especially in those with benign SQ metaplasia. These results suggest that EGF-R immunostaining is related to the endometrial cancer histotype regardless of the tumor grade or extent of miometrial invasion.

Adenocarcinoma↗
PubMed1994

Cytosolic free calcium concentration in the mitogenic stimulation of T lymphocytes by anti-CD3 monoclonal antibodies.

The effects of anti-CD3 monoclonal antibodies on cytosolic free Ca2+ concentration, [Ca2+]i, were investigated in freshly isolated lymphocytes, T cell lines, T clones and the leukemic T cell line Jurkat with three different methodologies, i.e. classical cuvette experiments, cytofluorimetry and videoimaging. With any technique, concentrations of anti-CD3 antibodies optimal for stimulation of DNA synthesis were completely ineffective at inducing early increases of [Ca2+]i in freshly isolated lymphocytes. At supraoptimal mitogenic concentrations: (i) anti-CD3 mAb induced negligible increases of [Ca2+]i when tested in suspensions of freshly isolated lymphocytes, but the response increased progressively during in vitro culturing with IL2; (ii) most, but not all, T clones, when tested in suspension, were responsive to these concentrations of anti-CD3 antibodies in terms of [Ca2+]i; (iii) using the videoimaging technique at the single cell level, it was demonstrated that the anti-CD3 antibodies induced large increases of [Ca2+]i in lymphocytes only under conditions which allowed adherence of the antibodies (and of the cells) to the glass surface. In all T cell types investigated, the [Ca2+]i increases were most often composed by multiple, asynchronous oscillations. The buffering of [Ca2+]i increases, obtained by loading the cells with membrane permeant esters of Quin-2 and Fura-2, inhibited anti-CD3 mAb induced DNA synthesis, but this appeared entirely attributable to a toxic side effect of the ester hydrolysis. The relevance of these data is discussed in terms of their methodological and functional implications for the understanding of the role of Ca2+ in mitogenic stimulation of T cells.

Aminoquinolines↗
PubMed1994

B and T cell function parameters during zidovudine treatment of human immunodeficiency virus-infected patients.

The aim of this study was to assess the effects of zidovudine on B cell dysregulation in human immunodeficiency virus (HIV)-infected patients and the phenomenon of gp 120/anti-gp 120 antibody complex adhesion to CD4+ cells. Compared with pretherapy figures, zidovudine treatment was not associated with a change in spontaneous in vitro synthesis of anti-HIV antibodies but was related to restoration of lymphocyte ability to produce Epstein-Barr virus-specific antibodies in 43% of previously unresponsive patients. After 30 days of therapy, the percentage of circulating CD4+/IgG+ lymphocytes decreased; the number of available CD4 receptors per cell increased, and antibodies to gp 120, evident in CD4+ cell eluates from most untreated patients, were no longer detectable. These results indicate that zidovudine partly restores in vitro humoral responsiveness but does not substantially influence the overall activation of the B cell compartment. The findings also suggest that zidovudine may down-regulate some immunopathologic phenomena that amplify direct viral damage.

Antigen-Antibody Complex↗
PubMed1993

B cell activation and human immunodeficiency virus infection. V. Phenotypic and functional alterations in CD5+ and CD5- B cell subsets.

B cell dysregulation is a hallmark of human immunodeficiency virus infection. Since B lymphocytes comprise two distinct subpopulations, CD5+ and CD5- cells, we addressed their individual phenotypic and functional behavior. Seropositive patients with both limited and advanced disease progression had an increased percentage of peripheral blood CD5+ B cells, compared to seronegative controls (20.1 +/- 2.1 and 22.7 +/- 5.7, respectively, vs 17.0 +/- 3.4 in controls); however, due to the lymphopenia and reduced number of circulating B cells in infected individuals, the absolute number of CD19+CD5+ lymphocytes was actually reduced. Although HIV-specific antibodies were synthesized spontaneously in vitro only by CD5- B cells, a 10-fold lower degree of spontaneous, non-HIV-specific activation was also displayed by unstimulated CD5+ B cells. These findings indicate that B cell dysregulation during HIV infection involves both the CD5- and the CD5+ B cell compartments; moreover, in view of the putative role of CD5+ B cells in autoimmune phenomena and IL-10 production, these data reinforce the possibility that B cell dysfunction might be causally involved in AIDS pathogenesis.

Acquired Immunodeficiency Syndrome↗
PubMed1992

CD4 epitope masking by gp120/anti-gp120 antibody complexes. A potential mechanism for CD4+ cell function down-regulation in AIDS patients.

The in vitro suppressive effect of gp120 and gp120/anti-gp120 antibody is well known but not yet proven to operate in vivo. We report findings consistent with the presence of gp120/anti-gp120 antibody complexes on CD4+ lymphocytes from HIV-infected patients with advanced disease. PBMC from most AIDS patients showed selective masking of the CD4 epitope associated with the gp120 binding site; immunoprecipitation of PBMC with anti-CD4 mAb disclosed high amounts of IgG bound to CD4 receptors. Antibodies against HIV env proteins, but not other HIV products or CD4 Ag, were detected in purified CD4+ cell culture supernatants; in vitro culture was associated with normalization of both CD4 expression in PBMC and the lymphocyte proliferative response to anti-CD3. gp120 presence could not be directly demonstrated, but findings strongly suggested that CD4+ lymphocytes from most HIV-infected patients with advanced disease were covered with gp120/anti-gp120 antibody complexes, which are responsible for down-regulation of surface CD4 expression as well as functional lymphocyte impairment; this event may represent an important mechanism in the pathogenesis of HIV-associated immunodeficiency.

Acquired Immunodeficiency Syndrome↗
PubMed1992

In vitro potentiation by lonidamine of the cytotoxic effect of adriamycin on primary and established breast cancer cell lines.

Lonidamine is a new potential chemotherapeutic agent, relatively non-toxic, that can positively modulate the efficacy of several antineoplastic drugs. We evaluated the response of two established human breast cancer cell lines (MCF-7 and BRC-230) and of 20 primary breast cancer cell lines to lonidamine, either alone or in combination with adriamycin, the drug most widely used in the management of breast cancer. Different schedules were tested by varying either concentration of the drugs (LND: 10-150 micrograms/ml; ADM: 0.10-0.15 micrograms/ml), or time of exposure (1-96 hours), or sequence of administration (ADM-->LND; LND-->ADM; ADM+LND). Our results indicate slight sensitivity of the cell lines to lonidamine when used alone, whereas an increase of efficacy was noted when lonidamine was added for at least 24 hours after a 4 hour exposure to adriamycin. Such efficacy was significantly greater than that expected from an additive effect between the two drugs. We conclude that lonidamine, when given according to an appropriate schedule, enhances, in vitro, the efficacy of adriamycin. A correct employment of lonidamine in the management of breast cancer might therefore potentiate the therapeutic effect of adriamycin.

Antineoplastic Agents↗
PubMed1992

Lymphoma induction by human B cells in scid mice.

Lymphoma development was studied in scid mice injected i.p. with PBMC from EBV-positive donors. Most injected mice developed oligo/monoclonal B-cell tumors within 4 months after the inoculation; EBV genome was found in tumor cells. Removal of T lymphocytes from the injected cell populations prevented lymphoma development in all mice, suggesting that T-cell-derived factors are involved in the expansion of the latently EBV-infected B-cell population within the immunodeficient host.

Animals↗
PubMed1991

An efficient method for culturing human breast epithelium: analysis of results.

We have examined the possibility of obtaining primary cultures from breast tissue utilizing a method especially developed for breast epithelium. The number of specimens able to grow in culture was very high: 82.8%, 64.3%, 75.0% and 77.8%, respectively, for primary breast cancer, skin recurrences, inflammatory breast cancer and normal breast tissue. In our experience, growth was not related to menopausal status or histopathologic type, whereas for skin recurrences, a prior pharmacologic treatment (chemotherapy) of the patient enhanced the growth capacity of the tissue. This culture method could help to study the basic biology of breast epithelia and to improve the chemotherapy approach of breast cancer patients.

Breast Neoplasms↗
PubMed1991

B cell activation during HIV-1 infection. II. Cell-to-cell interactions and cytokine requirement.

This study examined the mechanisms underlying the intense activation of HIV-1-specific B cells observed in peripheral blood of HIV-1-infected subjects. Spontaneous in vitro synthesis of anti-HIV-1 antibodies, as well as total Ig production, were dramatically reduced by accessory cell, but not T cell removal. This fall was counteracted by addition of rIL-6, but not other cytokines, to monocyte-depleted cultures; moreover, antisera against IL-6 suppressed spontaneous anti-HIV-1 antibody synthesis in a dose-dependent manner. Although IL-6 apparently sustained HIV-1-specific B cell activation, no increase in serum IL-6 levels was observed; PBMC from seropositive subjects did not produce increased amounts of IL-6 in vitro, compared to seronegative controls, both spontaneously and in the presence of LPS stimulation; finally, no constitutive expression of IL-6 gene could be documented in freshly isolated PBMC. These findings indicate that IL-6 may play a central role in HIV-1-specific B cell activation in seropositive patients, and further stress the importance of this cytokine during HIV-1 infection.

B-Lymphocytes↗
PubMed1991

Antigen detection, virus culture, polymerase chain reaction, and in vitro antibody production in the diagnosis of vertically transmitted HIV-1 infection.

Polymerase chain reaction (PCR), virus culture (V), antigen detection (Ag), and in vitro antibody production (IVAP) assays may be useful for the early detection of vertically transmitted HIV-1 infection in infants under 18 months of age, when a diagnosis cannot be based on seropositivity because of maternal antibody persistence. To assess the reliability of these procedures and to correlate diagnostic results with infection status, 101 children born to HIV-1-seropositive mothers were evaluated by all these techniques within the first 6 months of life. The children were then followed up to the age of at least 18 months, when diagnosis was made on the basis of AIDS or AIDS-related complex (ARC) onset or persistence of HIV-1 seropositivity. Out of 27 children classified as infected according to the above criteria, 25 (92.5%) were repeatedly positive in IVAP test, 22 (81.5%) in the first PCR analysis, and only 19 (70.3%) in the initial V assay. On further testing, a total of 24 children (88.9%) were found positive in PCR assay, and 23 (85.2%) in V test. All these assays were found to be more sensitive than antigen detection for HIV-1 infection diagnosis, but the antigenaemia was shown to be a useful prognostic marker of disease onset. We also found that both Ag and IVAP assays could give false-positive results in the first 2 months of life, which severely limits their diagnostic value during this period of time. False-positive results in PCR assay could occur at any time of the tested period and were unrelated to the child's age.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗
PubMed1991

B-cell activation during HIV-1 infection. III. Down-regulating effect of mitogens.

Spontaneous in vitro production of HIV-1-specific antibodies, a hallmark of infected subjects, is often down-regulated by the addition of pokeweed mitogen. We observed that a decrease in such ongoing anti-HIV-1 antibody synthesis could also be induced in cultures from most patients by addition of phytohemagglutinin and Concanavalin A, but not by Epstein-Barr virus, a selective B-cell mitogen. In most cases, this down-regulatory effect of mitogens was evident within the first 24 h of culture. The observed mitogen-associated decrease in spontaneous antibody synthesis was prevented by treating peripheral blood mononuclear cells with agents inhibiting non-major histocompatibility complex-restricted cytotoxic activity or by adding third-party cells to the cultures. In most cases, the mitogen-induced effect was also counteracted by removal of T lymphocytes or CD8+ T-cell sub-population. These findings recall a similar phenomenon observed in normal subjects following intentional immunization, and indicate that mitogen-induced down-regulation of spontaneous in vitro anti-HIV-1-antibody production most probably occurs through a lectin-dependent cytotoxic effect on activated B cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1990

Immune dysfunction in the elderly: effect of thymic hormone administration on several in vivo and in vitro immune function parameters.

The effects of short-term thymic hormone administration on age-associated immune function were evaluated. Two groups of individuals greater than 65 years of age were treated for 30 days with thymic extracts (TP1) or placebo; before and after this treatment a panel of in vitro and in vivo parameters was determined according to a very rigorous experimental protocol. In most individuals, TP1 treatment was associated with an improvement in cutaneous delayed-type response to PPD. Moreover, an increase in a circulating T cell subpopulation bearing the CD45R surface antigen ("virgin" T cells), and in NK cell cytotoxic activity was also observed in some subjects. Finally, lymphocyte responsiveness to PHA tended to increase, while no effect on lymphocyte ability to produce IL-2 following mitogen stimulation was observed. These findings suggest that TP1 treatment may influence age-related alterations in immune function parameters in some subjects.

Aged↗