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Biomedical subjects

P Musiani

Publications and source records attributed to P Musiani.

At least 127 records · Page 7Linked to original sources

Functional properties of human thymoma lymphocytes: role of subcellular factors in blastic activation.

The proliferative responses to phytohemagglutinin and the role of subcellular factors in the modulation of blastogenesis of thymoma lymphocytes from 5 thymoma patients were investigated. The addition of exogenous interleukin 1, a macrophage product, strongly augmented the blastic transformation of cultured thymocytes from both normal and neoplastic glands by influencing the production of interleukin 2 (IL-2) by a well-defined T-cell subset. The magnitudes of the blastic responses were ultimately modulated by the amount of IL-2 released in culture. The higher proliferative responses exhibited by thymocytes from thymoma were effectively sustained by a higher production of IL-2 in culture. In addition to having distinctive surface membrane receptors in common with normal thymocytes, thymoma lymphocytes were also under the influence of the same subcellular factors involved in T-cell blastic activation as thymocytes. These observations imply the presence of functionally distinct subpopulations in the thymoma lymphocyte component and add arguments in favor of their nonneoplastic nature.

Adult↗

Pseudolymphoma of the lung: lymphoid subsets in the lung mass and in peripheral blood.

Studies of the lymphocyte markers in a case of pseudolymphoma of the lung indicate a non-neoplastic nature of the lymphoid infiltrate. The relative proportions of T and B cells and of the markers for the various subsets of both populations reflect the morphologically mixed character of the cellular infiltrate of the lung mass. Moreover, an imbalance of T cell subsets was observed in the peripheral blood: the numbers of T cells with receptors for IgM (TM) were persistently decreased while an increase of the values of T lymphocytes with receptors for IgG (TG) was noted. In addition an altered immunologic status of the patient was indicated by the in vivo impairment of cellular immunity as demonstrated by the failure to respond to common antigens and to become sensitized to 1-chloro-2,4-dinitrobenzene (DNBC).

Adult↗

Human thymoma: immunologic characteristics of the lymphocytic component.

Several immunologic parameters were investigated in the lymphocytic component of ten thymomas, characterized by a variable degree of lymphocytic infiltration. The majority of thymoma lymphocytes are T-cell in nature, as are lymphocytes from the normal thymus. Lymphocytes from six thymomas with moderate or predominant lymphocytic infiltrates were capable of forming stable E-rosettes, (mean percentage +/- SD: 78.0 +/- 5.2); binding peanut agglutinin (67.3 +/- 8.6); and exhibiting receptors for the Fc-portion of IgM (21.8 +/- 6.0) at percentages that were close to those found in the normal thymus. On the other hand, lower numbers of stable E-rosetting cells (26.8 +/- 8.7), PNA-positive cells (27.5 +/- 12.4), and remarkably higher percentages of cells with receptors for IgM (54.0 +/- 4.2) were demonstrated by the lymphocytic population of four thymomas with scant lymphocyte components. In addition, lymphocytes from tumors with scant lymphocyte components show a higher proliferative response to phytomitogen (PHA), therefore exhibiting immunologic features comparable to those of the more mature pool of normal medullary thymocytes. The observed immunologic similarities between the populations of lymphocytes from thymomas and from the normal thymus gland suggest an exclusively epithelial origin of the thymoma.

Adult↗

Lymphocyte subsets in human thymus: expression of IgM-Fc receptor by peanut agglutinin positive and negative thymocytes.

The number of cells bearing receptors for the Fc portion of IgM (TM) and IgG (TG) has been evaluated in the human thymus. After overnight incubation the TM cells were 26.2 +/- 2.1% (mean +/- SE) in unfractionated thymus cell suspension, 23.4 +/- 3.8% in peanut agglutinin positive (PNA+) and 32.6 +/- 3.2% in PNA-negative (PNA-) fraction. PNA+ and PNA- fractions mainly consist of cortical and medullary thymocytes, respectively. The presence of TG was negligible. The fine structural features of TM cells from the thymus were very similar to those reported for TM lymphocytes from peripheral blood. In short-term culture a time-dependent increase of TM cells was observed. After 96 h of culture more than 60% of the thymocytes were shown to bear the Fc receptor of IgM. At the same time PNA+ and PNA- fractions expressed about 70% and 42% of TM cells respectively. The number of TG remained negligible. Our data indicate that in the human thymus there exists a distinct, quantitatively well-represented TM subset. Most probably, the peripheral TM cells derive from this subset which is present in both the cortex and the medulla of the thymus. Finally, the higher blastic responses to PHA exhibited by TM cells from PNA-subpopulation suggest that the most advanced intrathymic maturative step is attained by this distinct subset.

Agglutinins↗

Glucocorticoid receptors and in vitro corticosensitivity of peanut-positive and peanut-negative human thymocyte subpopulations.

In 6 human thymus glands, the immature subset of thymocytes was separated from the more mature one, by differential peanut lectin agglutination. These 2 cell subpopulations were analyzed for glucocorticoid receptor content by using a whole cell assay, with (3H)-triamcinolone acetonide as tracer. The unagglutinated thymocytes (peanut negative) contained about 2 times more receptor sites per cell than agglutinated (peanut positive) ones (7650 +/- 1550 S.D. verus 3195 +/- 896 S.D.). The affinity for steroid was similar in both cell subsets, as was the stereospecificity for glucocorticoids, the time-course of steroid-receptor association, and cytoplasmic to nuclear translocation. Despite the greater number of glucocorticoid receptor sites, the peanut-negative thymocyte subpopulation did not differ from the peanut-positive one in its sensitivity to the inhibitory effects of triamcinolone acetonide, as determined by measurements of the incorporation of radiolabeled precursors of protein and DNA. Moreover, the peanut-negative subset appeared more resistant in vitro to the steroid-induced cell lysis as compared to the peanut-positive one. Thus, our data suggest that glucocorticoid receptor density and corticosensitivity are not directly correlated and that the number of glucocorticoid receptor sites may be dependent on the degree of immunologic maturation.

Binding Sites↗

Imbalances in peripheral blood T-cell subpopulations in renal transplant patients.

The distribution of T-lymphocyte subpopulations bearing receptors for the Fc portion of IgG (TG) or IgM (TM) was monitored in 22 renal allograft recipients treated with immunosuppressive therapy and in 10 uraemic patients on haemodialysis. No significant difference in the distribution of T cells and T-cell subsets was found between normal controls and haemodialysed patients. In transplanted patients, however, a significant reduction of the total T-cell percentage (P less than 0.005), of TM subset percentage (P less than 0.025) and absolute number (P less than 0.005) and of TG absolute number (P less than 0.05) was observed. Considering patients with allografts functioning for more than 1 year only, the reduction in TM cells in terms of percentage (P less than 0.0005) and absolute number (P less than 0.025) was significant, while TG subset levels did not change significantly. In patients transplanted less than 1 year previous to our study, total T cells and T-cell subsets were reduced significantly only as absolute numbers. During the 1st year we observed several increments of TM values towards normal levels, especially in the first 2 months after transplantation. During this period, TM subset levels sharply increased at acute rejection crisis and returned to previous values with rejection reversal. Our results suggest that the TM subset plays a prominent role in the mechanisms involved in the immunological response to allografts, and therefore repeated TM cell monitoring could be useful in the follow-up of renal transplant patients.

Graft Rejection↗

Lymphocyte subpopulations in non-neoplastic thymus from myasthenia gravis patients.

Lymphocyte populations in non-neoplastic thymuses from fifteen patients with myasthenia gravis (MG) were examined. As in normal subjects, the great majority of thymic lymphocytes of MG patients are T cells. When MG thymuses were compared to normal glands, lower percentages of lymphocytes able to form E rosettes resistant to incubation at 37 degrees C (stable E rosettes) were found in MG thymuses. A negligible B cell content was detected in eight normal and in eight MG thymuses with absent or rare lymph follicles; but there was a substantial B cell presence in the thymuses of seven MG cases with thymic hyperplasia containing many germinal centres. Normal and MG thymuses contain the same percentage of lymphocytes bearing receptors for the Fc portion of IgM (TM). Moreover, the IgM Fc receptor was found mostly on cells which did not form stable E rosettes and did not bear surface immunoglobulin. The possible significance of these findings is discussed.

Adolescent↗

FC receptor for IgM: factors influencing detection on human T lymphocytes.

This paper is concerned with technical standardization in detecting Fc-IgM receptors on human T lymphocytes. We have investigated a number of factors of critical importance in obtaining easily reproducible and reliable estimates of the numbers of TM cells among human peripheral T lymphocytes. A point of major importance is optimal coating of erythrocytes by IgM molecules. For this condition to be met, particular attention is required when erythrocytes from animals other than the one used for obtaining antiserum are used to prepare EA-IgM. Determination of the agglutinating titer of IgM preparation is useful in determing optimal sensitizing dilutions. Full expression of Fc receptors is favoured when human cord serum is added to the medium. The influence of incubation period of EA-lymphocytes mixtures on TM counts has also been investigated.

Animals↗

T-cell nature of leukaemic cells in a case of Sézary's syndrome with 'null-cell' features.

alpha-naphthyl acetate esterase (ANAE) activity has been investigated in leukaemic cells from peripheral blood in a typical small-cell Sézary syndrome (SS) case in which cerebriform mononuclear cells failed to form E rosettes. The 'dot-like' ANAE positivity found in the majority of these neoplastic cells strongly supports a T-cell origin. In addition, a non-monocytic, non-B-cell nature of Sézary cells is indicated by the lack of Ia-like antigens. Finally, there is evidence of a distinct portion of Sézary cells simultaneously expressing ANAE activity and Fc IgM receptors.

Esterases↗

Structural and functional characteristics of hairy cells.

Morphological, cytochemical, immunological and ultrastructural studies were performed on peripheral blood mononuclear cells from a patient with hairy-cell leukemia. Immunofluorescence studies showed a very strong intensity of fluorescence and indicated that hairy cells had monoclonal surface-membrane immunoglobulins (SmIg) actively produced by the cells. An unusual spontaneous SmIg redistribution induced by antibodies was also noted. Immunoultrastructural studies demonstrated that antibody-induced redistribution of SmIg on hairy cells is in form of a singular polar cap and that the cell membrane is rapidly cleaned of the complexes by endocytosis. The behavior of hairy cells regarding several membrane markers, mitogen stimulation and antibody-induced cytotoxicity suggests that hairy projections could represent the expression of a functional stage common to different lymphocyte subpopulations, or alternatively, a marker of a peculiar subset of B lymphocytes.

Antibodies, Neoplasm↗

Subpopulations of T lymphocytes in myasthenia gravis patients.

Subpopulations of human peripheral blood T lymphocytes were examined in twenty-three myasthenic patients. T lymphocytes bearing receptors for the Fc portion of IgG (T gamma) were significantly increased in a third of the patients examined. T lymphocytes bearing receptors for the Fc portion of IgM (Tmu) were within normal values in all but two patients. Possible implications of these cells in the pathogenesis of myasthenia gravis are discussed.

Adolescent↗

Subpopulations of lymphocytes in human thymomas.

Lymphocyte populations in six normal thymuses and ten thymomas were examined. The majority of lymphocytes from both thymus and thymoma differ from peripheral T lymphocytes in their capacity to form E-rosettes resistant to incubation at 37 degrees C. Low percentages of T lymphocytes bearing receptors for the Fc portion of IgG (TG) and IgM (TM) were found in normal thymus. In contrast, lymphocytes from five out of nine thymomas showed remarkable percentages of TM cells. Compared with normal thymocytes, lymphocytes from seven out of ten thymomas responded vigorously to mitogens. The possible origin and nature of thymoma lymphocytes are discussed.

Adult↗

Specificities of rabbit anti-human insulin receptor antibodies.

Human insulin receptors obtained from normal human placentae were highly purified by affinity chromatography and used to immunize rabbits. The immunological response was evaluated in order to reveal the presence of antibodies blocking the binding of insulin to monocytes of normal subjects. Since no blocking activity was found IgG from rabbits were coupled to agarose in order to evaluate the presence of antibodies directed to determinant(s) other than the insulin binding site. One rabbit was found to produce antibodies binding the insulin receptor on a site different from the insulin binding site.

Animals↗

Inhibitory activity of alpha-1-antitrypsin bound to human IgA.

Complexes between alpha-1-antitrypsin (alpha 1AT) and monoclonal IgA are regularly demonstrable in the plasma of myeloma patients. These alpha 1AT-IgA complexes, free of contamination by unbound alpha 1AT, are purified from 5 myeloma patients sera using salt-mediated hydrophobic chromatography. The complexes have a molecular weight greater than or equal to 400 000: this suggests that alpha 1AT is bound to di- or polymeric IgA. The alpha 1AT bound to IgA constitutes the 3.2, 3.5, 7.2, 8.5, and 24.6 per cent of the total alpha 1AT present in the 5 myeloma serum samples. There is a linear correlation between bound alpha 1AT concentration and IgA level in the range of the IgA concentrations considered (r = 0.988; p less than 0.05). Similar values are obtained quantitating bound alpha 1AT by radioimmunodiffusion technique or by determination of the trypsin-inhibiting capacity; this demonstrates that the bound alpha 1AT fully retains its inhibitory capacity. The biological significant of this binding phenomenon is discussed.

Chromatography, Gel↗

Alpha-1-antitrypsin in umbilical cord serum: pi phenotypes and relationships with idiopathic respiratory distress syndrome.

The concentrations and phenotypes of serum alpha-1-antitrypsin (alpha1AT) were determined in 650 newborn infants. The distribution of these 650 subjects among the various Pi phenotypes confirms the higher frequency reported for the PiS allele in Latin populations. Serum alpha1AT levels vary between one phenotype and the other. Besides, at birth, infants weighing more than 2,500 g have alpha1AT levels significantly higher (P less than 0.001) than infants weighing less than 2,500 g; this difference in serum alpha1AT concentrations is due to the low alpha1AT levels found in preterm infants. The significantly lower alpha1AT concentrations found in preterms is associated with a higher risk of developing IRDS and with a mean birth weight under 2,000 g. Infants who develop IRDS frequently have lower alpha1AT levels than those who do not develop the syndrome, independently from body weight. On the basis of serum alpha1AT quantitation, newborn infants may be separated into two groups, characterized respectively by concentrations above or below 150 mg%. From our data, it appears that if the group with an alpha1AT concentration lower than 150 mg% is phenotyped, it is possible to differentiate infants with a high risk of fatal IRDS from individuals with a "pathological" phenotype.

Birth Weight↗