Search PubMed⌕ Search

Biomedical subjects

L Marini

Publications and source records attributed to L Marini.

At least 37 records · Page 2Linked to original sources

Three cortical stages of colour processing in the human brain.

We used the technique of functional magnetic resonance imaging to chart the colour pathways in the human brain beyond V4. We asked subjects to view objects that were dressed in natural and unnatural colours as well as their achromatic counterparts and compared the activity produced in the brain by each condition. The results showed that both naturally and unnaturally coloured objects activate a pathway extending from V1 to V4, though not overlapping totally the activity produced by viewing abstract coloured Mondrian scenes. Normally coloured objects activated, in addition, more anterior parts of the fusiform gyrus, the hippocampus and the ventrolateral frontal cortex. Abnormally coloured objects, by contrast, activated the dorsolateral frontal cortex. A study of the cortical covariation produced by these activations revealed that activity in large parts of the occipital lobe covaried with each. These results, considered against the background of previous physiological and clinical studies, allow us to discern three broad cortical stages of colour processing in the human brain. The first is based on V1 and possibly V2 and is concerned mainly with registering the presence and intensity of different wavelengths, and with wavelength differencing. The second stage is based on V4 and is concerned with automatic colour constancy operations, without regard to memory, judgement and learning. The third stage, based on the inferior temporal and frontal cortex, is more concerned with object colours. The results we report, as well as the schema that we suggest, also allow us to reconcile the computational theory of Land, implemented without regard to cognitive factors such as memory and learning, and the cognitive systems of Helmholtz and Hering, which view such factors as critical in the determination of colours.

Adult↗

Changes in antigen expression on B lymphocytes during HIV infection.

Involvement of the B cell compartment during HIV infection plays an important role in the development of immune deficiency. The aim of this study was the identification of specific antigen expression changes on B lymphocytes in HIV infection as surrogate markers in this cell population of certain functional aspects that could be easily measured. We investigated the level of expression of a series of constitutive surface markers in B lymphocytes (HLA-DR, CD19, CD20, CD21, CD22) from 30 HIV-seropositive adult patients and 20 normal controls. By means of quantitative flow cytometry, we assessed the number of antigen molecules per cell using standard beads to convert fluorescence intensity into antibody-binding capacity (ABC). We correlated these results with disease stage and cellular markers of immune activation. The expression of CD20 was significantly increased when B cells from HIV-infected individuals were compared with those from uninfected subjects. No differences were found in the density expression of HLA-DR on activated CD3+ T cells between HIV+ and HIV- subjects. In contrast, B cells from HIV+ patients showed a significantly lower number of HLA-DR molecules per cell compared to normal controls. A significantly lower number of CD21 molecules per cell was also found on B lymphocytes from HIV+ patients compared to normal controls. No differences in CD19 and CD22 expression levels on B cells between HIV-infected patients and controls were detected. No differences between HIV disease stages were detected for CD19, HLA-DR, CD21 and CD22. In contrast, differences between stages were found for CD20 expression, which showed significant changes in individuals with less than 200 CD4 T cells/microl. The data presented here demonstrate that B lymphocytes of HIV-infected individuals exhibit specific changes in receptor density expression during HIV infection and that these changes are often correlated with progression of disease, as measured by CD4 counts. No correlations were found between the percentages of HLA-DR+ T cells and the ABC values of the B cell markers studied. These antigen expression modulations may contribute to the humoral abnormalities during HIV infection and to the development of severe, recurrent or multiple bacterial infections. Therefore, quantitative flow cytometry may be of value in HIV infection both for clinical and biological studies. The study of antigen density changes on B cells in HIV infection may allow a better understanding of the humoral immune defects observed in these patients and provide insights into the functional defects of B cell compartment in HIV-infected individuals.

Adult↗

Altered lymphocyte antigen expressions in HIV infection: a study by quantitative flow cytometry.

To identify surface antigen changes that may contribute to the immune deficiency in infection with the human immunodeficiency virus (HIV), we quantified, by double-staining flow cytometry, the number of antigens of the main peripheral blood lymphocyte subsets from 30 HIV-positive persons and compared them with those of 19 HIV-negative healthy donors. Standard microbeads with different capacities to bind mouse immunoglobulins were used to convert the mean fluorescence intensity values into numbers of antigen molecules per cell, measured as antibody binding capacity. The level of expression of different lymphocyte antigens in HIV-infected patients differs from that seen in normal blood lymphocytes. Some of these surface markers are decreased, whereas others are increased, and their expression is modulated depending on the specific cell subset considered. The expression of CD3, CD4, and CD8 on T lymphocytes is significantly decreased; moreover, CD3 is down-regulated on activated and nonactivated T lymphocytes and on CD4 and CD8 cells. In contrast, the expression of CD2 on T cells is significantly increased. Natural killer cells exhibit down-regulation of CD7, normal levels of CD8 and CD56, and overexpression of CD2. Our results also identified, for most of these antigens, quantitative differences in membrane expression according to different disease stages, as assessed by the CD4 T-cell count. Quantitative flow cytometry therefore may provide useful insights into the lymphocyte functional defects characterizing HIV infection.

Adult↗

Activated naive and memory CD4+ and CD8+ subsets in different stages of HIV infection.

The aim of this study was to evaluate the changes and the correlations between the main lymphoid phenotypes indicative of activation and/or functional states during the course of HIV infection. Immunophenotype studies by flow cytometry were performed on blood samples from 59 HIV-1-positive patients, divided into four stages, and 18 seronegative healthy controls, to determine the expression of HLA-DR, CD29 and CD45RA on CD4+ and CD8+ lymphocytes. HLA-DR expression was elevated on the total lymphocyte population and in both the main T subsets. Its presence on CD4+ lymphocytes probably has a different significance in the first phase of infection when it is indicative of reactive activation, in contrast to the more advanced stages of disease when it favors the spread of HIV infection among this cellular subset. The increasing state of immune activation is also confirmed by a proportional decrease in the expression of CD45RA, substantial stability of CD29 and an increase in double-negative CD4+ cells as the infection proceeds. Also CD8+HLA-DR+ lymphocytes increase during the course of disease. The parallel increase of the CD8+CD45RA+ subset in asymptomatic patients suggests the presence in this phase of infection of peripheral blood immature and activated CD8+ cells. Similarly to CD4+, the CD29 subset of CD8+ lymphocytes remains unchanged compared to controls during disease progression. In both CD4+ and CD8+ subsets we observed the increase of a double-negative sub-population of uncertain significance. HLA-DR, the memory marker CD29 and the naive marker CD45RA seem to be the more promising and helpful indicators for a better staging of disease and may provide information that accurately correlates with progression of infection. The peculiar trend of the described phenotypic alterations could represent changes in the immune response to HIV during disease progression and facilitate the definition of specific immune patterns in different stages of HIV infection.

Adult↗

[Clinical uses of flow cytometry in hematological oncology].

In the last decades, the classification of schemes of haematological malignancies have undergone considerable changes both in terms of modifications of previous concepts and of methodological approaches, in parallel with the acquisition of new information on the physiopathological and functional pattern of haemic cells and of their precursors both at the lymph node and bone marrow level. The cyto-morphological aspects of haemic were better defined and integrated by the application of cyto- and histochemical methods, which were subsequently supplemented by bioenzymatic and cytogenetic techniques, then by immunophenotypical studies and finally by biomolecular investigations. Through the use of monoclonal antibodies and the introduction both in research and routine diagnostic practice of multiparameter analysis techniques, it is now possible to correlate several cellular parameters, to identify clonality of malignant cells as well as their lineage assignment and maturation stage. Flow cytometry has become an important, rapid and objective method for the diagnosis of haematological neoplasias. In the present survey we have illustrated the different expression of surface, cytoplasmic and nuclear antigens in haematological malignancies, their correlation with the clinical course of the disease and their diagnostic and prognostic significance.

Antibodies, Monoclonal↗

Oncogene expression is modulated by recombinant human interferon-beta in human breast-cancer cells.

The effect of recombinant human interferon-beta on growth and oncoprotein expression was investigated in several human breast-cancer cell lines with different characteristics. All cell lines tested were sensitive to the antiproliferative action of the drug, regardless of their estrogen sensitivity. The maximal inhibition of cell proliferation was seen after 6 days of treatment. In estrogen-sensitive CG-5 and ZR-75-1 cells, but not in MDA-MB-453 estrogen-insensitive cells, a reduction in c-myc and c-erbB2 oncoproteins occurred after 48-72 hr and became more pronounced after 120-168 hr of treatment, suggesting that this down-regulation is not direct but is mediated by undefined molecular mechanisms. The time-course of the IFN-mediated decrease in oncoproteins seems to indicate that this event is not strictly related to the IFN-regulation of cell proliferation. The expression of c-erbB2 and c-myc was also analyzed, after recombinant human interferon-beta treatment, at the mRNA level in CG-5 cells. Surprisingly, no statistically significant variation of c-erbB2 or of c-myc mRNA was found either before or after 120-168 hr. Thus, we surmise that the observed reduction of oncoproteins may be due to post-transcriptional mechanisms.

Antineoplastic Agents↗

Combined effects of estradiol, leuprorelin, tamoxifen and medroxyprogesterone acetate on cell growth and steroid hormone receptors in breast cancer cells.

Both tamoxifen and medroxyprogesterone acetate have a direct antitumor effect and are widely used in breast cancer therapy. Luteinizing-hormone-releasing hormone analogs inhibit the growth of breast cancer cells and could represent an alternative treatment for patients affected by breast cancer. Our study was carried out to investigate the effect of leuprorelin (TAP-144) alone or combined with tamoxifen or medroxyprogesterone acetate in human breast cancer cells. Ineffective when used in the absence of estrogens, TAP-144 inhibited the estrogen-stimulated growth of MCF-7, CG-5 and ZR-75-1 cells cultured in medium supplemented with charcoal-treated serum. The growth of estrogen-unresponsive MDA-MB-231 cells was not affected by TAP-144. The combination of TAP-144 with tamoxifen in CG-5 cells did not determine any enhancement of inhibition of cell growth, whereas in both CG-5 and MCF-7 cells, when 1 microM TAP-144 was associated with 0.1 microM medroxyprogesterone acetate, cell growth inhibition was increased, resulting in a subadditive effect. Progesterone receptor levels of CG-5 cells were significantly increased by TAP-144 in the presence of 17 beta-estradiol with respect to those present in control and 17 beta-estradiol-treated cells.

Breast Neoplasms↗

[Relapsing polychondritis. Review].

Using a clinical case which was brought to their attention as a starting point, the authors reexamine the problems relating to the nosographic, etiological, pathogenetic, pathoanatomical and clinical aspects of relapsing polychondritis, as well as those concerning its differential diagnosis and therapy. In particular, they review the various theories of immunological pathogenesis related to the alterations in collagen observed in relapsing polychondritis and in other correlated diseases.

Collagen↗

Neoplastic phlebothrombosis from renal vein to right atrium: a case report.

The authors present an atypical case of neoplastic thrombosis of the great abdominal veins, evaluated with echo-Doppler duplex scanner and computed tomographic scan with contrast enhancement. In this report the authors stress again the diagnostic accuracy of echo-Doppler methods in the study of such a phlebopathy. They describe its sonographic differential diagnosis from acute or chronic idiopathic phlebothrombosis.

Aged↗

[Idiopathic hypereosinophilia syndrome: description of a clinical case and review of the literature].

Idiopathic hypereosinophilia is a disease with an unknown etiology and pathogenesis and uncertain nosographic classification, although there is now tendency to group a number of syndromes under this name which were previously classified separately, although having similar hematological symptoms and clinical manifestations. The paper examines these aspects and reports the case of a patient with idiopathic hypereosinophilia to steroid treatment.

Diagnosis, Differential↗

Antiproliferative effect of leuprorelin acetate, alone or combined with tamoxifen or medroxyprogesterone acetate, on human breast cancer cell lines.

We have investigated the antiproliferative action of leuprorelin acetate (TAP-144) on human breast cancer cells, cultured in medium supplemented with charcoal-treated fetal calf serum. The analogue had no effect on cell growth of oestrogen receptor-negative MDA-MB-231 cells. Although ineffective when used alone, TAP-144 inhibited in a dose-dependent fashion the oestradiol-induced cell growth in oestrogen receptor-positive and oestrogen-sensitive MCF-7, ZR-75-1 and CG-5 cells. TAP-144 did not modify the growth inhibitory activity of tamoxifen on CG-5 cells. A high concentration of TAP-144 (10(-6) M) seemed to increase the antioestrogenic effect of medroxyprogesterone acetate (MPA) (10(-7) M) in the same model. The data reported indicate that, in our culture conditions, TAP-144 has a direct antitumour effect on breast tumour cells. Our findings concerning the promotion of the antiproliferative effect of MPA merit further investigation.

Antineoplastic Agents↗

Structural or functional heterogeneity of normal human serum albumin, allo albumin, bisalbumin.

The present paper reports a comparative isoelectric focusing study of electrophoretically normal and abnormal albumins. All the albumins were purified by two different techniques (cellulose acetate electrophoresis and preparative slab isoelectric focusing), and submitted to analytical isoelectric focusing before and after incubation with either metabolites or drugs. Isoelectric focusing patterns show general heterogeneity, both in normal and in any of the observed alloalbumins. The heterogeneity is increased in bisalbumins (drug or metabolite induced), showing the same electrophoretic pattern as alloalbumins. The differences are related to the amount of the ligands. The results agree with the hypothesis that the heterogeneity depends on the structure and the carrier function of albumin.

Albumins↗

A novel protocol that allows short-term stem cell expansion of both committed and pluripotent hematopoietic progenitor cells suitable for clinical use.

To obtain long-term engraftment and hematopoiesis in myeloablated patients, the cell population used for hematopoietic reconstitution should include a sufficient number of early pluripotent hematopoietic stem cells (HSCs), along with committed cells from the various lineages. For this purpose, the small subset of CD34+ cells purified from different sources must be expanded ex vivo. Since cytokines may induce both proliferation and differentiation, expansion would provide a cell population comprising committed as well as uncommitted cells. Optimization of HSC expansion methods could be obtained by a combination of cytokines able to sustain renewal of pluripotent cells yet endowed with poor differentiation potential. We used variations of the combinations of cytokines described by Brugger et al. [W. Brugger, S. Heimfels, R. J. Berenson, R. Mertelsmann, and L. Kanz (1995) N. Engl. J. Med. 333, 283-287] and Piacibello et al. [W. Piacibello, F. Sanavio, L. Garetto, A. Severino, D. Bergandi, J. Ferrario, F. Fagioli, M. Berger, and M. Aglietta (1997) Blood 89, 2644-2653] to expand UCB CD34+ cells and monitored proliferation rate and phenotype after 14 days of culture. Several hematopoietic lineage-associated surface antigens were evaluated. Our data show that flt3L and thrombopoietin in combination with IL-3, while sustaining a high CD34+ proliferation rate, provide a relatively low enrichment in very early uncommitted CD34+/CD38- cells. Conversely, in the absence of IL-3, they are less effective in inducing proliferation yet significantly increase the number of CD34+/CD38- cells. A combination of the above protocols, applied simultaneously to aliquots of the same sample, would allow expansion of both committed and pluripotent HSC. This strategy may represent a significant improvement for clinical applications.

ADP-ribosyl Cyclase↗