Biomedical subjects
F Scalise
Publications and source records attributed to F Scalise.
Lymphocytes bearing the gamma delta T cell receptor in acute Brucella melitensis infection.
A phenotypical analysis carried out by indirect immunofluorescence and two-color cytofluorometry showed that the number of lymphocytes bearing the gamma delta T cell receptor (TcR) heterodimer was dramatically increased in the blood of six children with Brucella melitensis infection. Most in vivo expanded gamma delta T cells reacted with a monoclonal antibody which identifies V delta 2 gene products and a significant proportion expressed CD25 and HLA-DR activation antigens. In addition, whereas only a few gamma delta T lymphocytes were CD8+, nearly all were CD4-. Highly enriched populations of both alpha beta and gamma delta T cells were obtained by negative immunoselection from three subjects with brucellosis sampled during convalescence. Despite the different form of their TcR, the proliferation of these two major T cell subsets in response to a mitogenic anti-CD3 monoclonal reagent (OKT3) was optimal. In contrast, alpha beta, but not gamma delta, T lymphocytes proliferated vigorously in response to the antigenic stimulus elicited by heat-killed Brucella. Further studies are, therefore, needed to determine whether the selective expansion of the gamma delta T cell subpopulation observed during the clinical course of the infection is driven by antigenic determinant(s) borne by the pathogen in vivo or is due to host-derived stimuli, such as autologous heat-shock proteins expressed on the surface of the infected cells.
Mycobacteria-reactive gamma/delta T cells are present in human colostrum from tuberculin-positive, but not tuberculin-negative nursing mothers.
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Human milk T lymphocytes are mostly HML-1-positive cells.
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Lymphocytes bearing the gamma/delta T-cell receptors in Down's syndrome.
Subjects with Down's syndrome (DS), or trisomy 21, have an increased susceptibility to infections, malignant diseases and autoimmune phenomena. Various arms of the immune system are severely impaired in trisomic patients. We found that the proportion of blood lymphocytes bearing the gamma/delta T-cell receptor (TCR) was significantly higher in adults with trisomy 21 than in age- and sex-matched healthy controls. Interestingly, the increase was mainly due to an over-expansion of cells which bear non-covalently bound gamma/delta chains on their surface. This contrasts with the normal blood picture, where the great majority of gamma/delta T cells express the disulphide-linked form of the TCR. The fact that trisomic gamma/delta T cells are both numerically and phenotypically unbalanced provides further evidence that immunological abnormalities are integral features of DS.
Influence of age and sex on left ventricular anatomy and function in normals.
Using digitized M-mode echograms, we evaluated the influence of sex on age-related changes of left ventricular (LV) anatomy and function in a normal population (75 males and 75 females, subdivided in age groups for each decade from 20 to 70 years). Aging is accompanied with an increase in septal and wall thickness in both males and females and in LV diameter only in males, with a progressive increase of LV mass more pronounced in males than in females. As regards LV function we found a progressive slowing of relaxation in females and of both contraction and relaxation in males, not related to changes in LV mass.
Lymphocytes bearing the gamma delta T-cell receptor in acute toxoplasmosis.
Although the relative and absolute numbers of CD3+ cells (T lymphocytes) were similar in eight children with acquired Toxoplasma gondii infection and 10 uninfected age- and sex-matched healthy controls, the proportion of cells bearing the gamma delta T-cell receptor was significantly higher in the subjects with acute toxoplasmosis. The great majority of gamma delta T cells from the infected patients expressed covalently bound gamma delta chains on their surface, i.e. were BB3+ lymphocytes. Since the gamma delta T-cell subsets exert both restricted and unrestricted major histocompatibility complex cytotoxicity, further research is needed to elucidate the role of gamma delta T cells in the control of this coccidian protozoan infection.
Double-blind comparison of perindopril and captopril in hypertension. Effects on left ventricular morphology and function.
Using digitized M-mode echocardiograms, we compared, in a double-blind study, the effects of 4 to 8 mg perindopril given once daily and 25 to 50 mg captopril given twice daily on the left ventricle (LV) in 20 hypertensive patients. Both treatments significantly (P less than .001) lowered blood pressure, reducing systemic vascular resistances. After 3 months both drugs induced a comparable percentage of reduction in LV mass, with an increase in the peak rate of LV relaxation and no changes in the peak rate of LV contraction. Our results demonstrate that perindopril once daily is an effective antihypertensive agent; it is also able, like captopril, to induce regression of LV hypertrophy, with improvement in diastolic performance and no deterioration in ventricular systolic function.
"Memory" T cells in human breast milk.
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Gamma-delta T cells in human breast milk.
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T-lymphocyte activation pathways in alcoholic liver disease.
Immune system derangement in cirrhotic patients with evidence of malnutrition is a well-recognized characteristic of chronic alcohol abuse. However, in vitro studies on cellular immune function performed with lectin mitogens have produced conflicting results. The recent development of more accurate immunological techniques for studying lymphocyte transformation, that use monoclonal antibodies directed against surface structures (CD3 and CD2) involved in antigen recognition, as well in adhesion functions, prompted us to study discrete in vitro T-cell hypo-responsiveness in a series of alcoholic liver disease (ALD) patients with no evidence of malnutrition or hepatic cirrhosis. The results indicated that the CD2 pathway is markedly defective in ALD T lymphocytes, accompanied by reduced interleukin-2 (IL-2) receptor expression upon in vitro activation. This defect cannot be reversed by the addition of recombinant IL-2 (rIL-2) or rIL-1. Faulty intracellular signal transduction by protein kinase C (PKC) and defective intracellular Ca2+ mobilization may be responsible for the CD2 pathway impairment. The addition of small amounts of phorbol 12-myristate, 13-acetate, but not Ca2+ ionophore A23187, is able to overcome the defect, thereby suggesting a direct PKC involvement. The hypothesis of a direct ethanol effect on transmembrane signal transduction systems is suggested by the demonstration of an expansion of circulating virgin (naive) T cells (CD3+/UCHL1-low) that binds tyrosine phosphatase (CD45RA antigen) on their surface.
Human milk lymphocytes bearing the gamma/delta T-cell receptor are mostly delta TCS1-positive cells.
Our laboratories previously reported that the proportion of lymphocytes bearing the gamma/delta T-cell receptor (TcR) is twofold greater in human milk lymphocyte suspensions than in autologous and heterologous blood samples. The present investigation shows that gamma/delta colostral T cells preferentially express non-covalently bound gamma/delta chains, whereas only a few display the disulphide-linked form of the TcR. This contrasts with the picture in the blood, where the distribution of these two nonoverlapping subpopulations is proportionally inverse. These findings are further evidence that the colonization of the mammary gland during lactation by immune system cells is the result of a selective homing process.
Human breast milk T lymphocytes display the phenotype and functional characteristics of memory T cells.
Naive (unsensitized) and memory (antigen-primed) T cells can be phenotypically distinguished on the basis of the high or low intensity with which they express a number of immunologically relevant lymphocyte membrane antigens, including CD45R, CDw29, UCHL1, LFA-1, LFA-3, CD2 and Pgp-1. Here we report that in contrast to the two major T cell subsets found in the blood, milk T lymphocytes are almost exclusively composed of the one which exhibits the CD45Rlow, CDw29, UCHL1, LFA-1high memory T cell phenotype. In addition, while milk and autologous blood cells expressed similar levels of CD3 surface antigens, CD2 and ICAM-1 expression was approximately twofold greater on the milk T lymphocytes. This agrees with the finding that whereas colostrum T cells respond poorly to PHA, they proliferate and produce interferon-gamma normally when stimulated with either the anti-CD3 or anti-CD2 monoclonal antibodies. The selective colonization of the mammary gland during lactation by a population of T lymphocytes which displays the phenotype and functional characteristics of memory T cells may be one of the mechanisms whereby the suckling infant benefits form its mother's immunological experience.
Lymphocytes bearing the T cell receptor gamma delta in human breast milk.
Lymphocytes bearing the T cell receptor gamma delta (TCR-gamma delta) were searched for in human early milk lymphocyte suspensions by two colour cytofluorimetric analysis. It was found that the proportion of TCR-gamma delta+ cells was twofold greater in colostrum than in either autologous or heterologous blood samples. Additional studies are needed to determine whether this particular subset of lymphocytes is involved in the lactation transmission of cellular immunity.
[Factors influencing left ventricular function in arterial hypertension].
Using digitized M-mode echograms we evaluated the role of preload, afterload, inotropic state and left ventricular (LV) mass on LV systolic and diastolic function in 2 groups of hypertensive patients: Group 1: 25 subjects (18 men, mean age 48 +/- 6 years) with normal LV mass (less than 230 g); Group 2: 25 subjects (20 men, mean age 50 +/- 8 years) with LV hypertrophy (wall hypertrophy with normal LV diameter). As control group, we evaluated 50 normal subjects, matched for age, sex and body surface area with hypertensives. LV mass was significantly (p less than 0.001) higher as respect to normals also in hypertensives with normal LV mass; indexes of LV systolic and diastolic function were similar in normals and in hypertensives with normal LV mass and significantly lower in subjects with LV hypertrophy. The end-systolic wall stress was not significantly different in the 2 groups of hypertensives. We evaluated the relative role of preload (end-diastolic LV diameter), afterload (end-systolic wall stress) inotropic state (systolic arterial pressure/end-systolic LV diameter) and LV mass on LV systolic and diastolic function using multiple regression analysis. As regards LV systolic function, the major determinant was the systolic pressure/end-systolic diameter ratio in normals, the end-systolic stress in hypertensives. As regards LV diastolic function, the major determinant was end-systolic stress in normals and hypertensives with normal LV mass, LV mass in hypertensives with myocardial hypertrophy. Preload seems not to influence LV function in normals and in hypertensives with normal LV diastolic diameter. The major determinant of LV systolic function is the inotropic state in normals and the afterload in hypertensives.(ABSTRACT TRUNCATED AT 250 WORDS)
T-cell response to phorbol ester PMA and calcium ionophore A23187 in Down's syndrome.
The proliferative response of purified T cells to anti-CD2 monoclonal antibodies (T112 plus T113) was found to be markedly reduced in 12 subjects with Down's syndrome (DS). The addition of phorbol ester PMA, which activates Ca2+/phospholipid-dependent enzyme protein kinase C, or calcium ionophore A23187, which increases intracytosolic free Ca2+ concentration, enhanced, but did not normalize, the defective anti-CD2-mediated T-cell mitogenesis. In contrast, the proliferation of resting lymphocytes from trisomic patients was comparable to that of the control cells when PMA and A23187 were used as co-blastogenic reagents. Because PMA and A23187 together bypass the early activation pathways and promote T-cell growth through the direct induction of membrane interleukin 2 (IL-2) receptor expression and IL-2 synthesis and secretion, it could reasonably be hypothesized that the faulty DS T-cell activation induced by antigen or mitogen is due to a deranged transmembrane signal transduction, rather than a defect in the later intracellular events.
[Recent findings on the phenotype and function of T-lymphocytes in the human colostrum].
Recent studies in our laboratory have demonstrated that the great majority of human colostral T cells display the phenotypic and functional characteristics of memory T lymphocytes, e.g. were able to proliferate in response to anti-CD3 and anti-CD2 monoclonal antibodies, and to a lesser extent, to the lectin mitogen phytohaemagglutinin. In addition, their production of interferon-gamma after anti-CD3 and anti-CD2 stimuli was similar to that calculated in autologous blood lymphocyte cultures. More interestingly, the proportion of T lymphocytes bearing the gamma/delta T-cell receptor was found to be significantly higher in the mammary secretion than in autologous and heterologous blood samples. Furthermore, these cells were mostly delta-TCS-1+, thereby suggesting that they are actively motile cells capable of migrating from lymphoid to extra-lymphoid body tissues. The fact that the phenotypic pattern of colostral gamma/delta T cells is similar, if not identical, to that of the intestinal intraepithelial counterpart suggests that these cells might originate in the gut-associated lymphoid system and home selectively to the mammary gland late in pregnancy and throughout lactation. However, additional studies are needed to confirm whether milk T lymphocytes are actively involved in the adoptive lactation transmission of cellular immunity to the suckling infant.