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Biomedical subjects

E Maggi

Publications and source records attributed to E Maggi.

At least 199 records · Page 11Linked to original sources

IgE synthesis in vitro induced by T cell factors from patients with elevated serum IgE levels.

The effect of unstimulated T cell culture supernatants (TCS) from patients with atopic dermatitis and high serum IgE levels on the IgE production in vitro by B cell rich suspensions from normal individuals or grass pollen sensitive patients with mild atopy was evaluated. TCS from patients with raised IgE enabled B cell suspensions from normal individuals to produce detectable amounts of IgE and potentiated the spontaneous IgE synthesis in vitro by B cell suspensions from grass sensitive patients. In contrast, the addition of TCS from normal subjects with low serum IgE levels did not increase or even reduced IgE synthesis by B cell cultures. When the same B cell cultures were analysed for their ability to produce IgG or IgM protein, no significant differences were observed. These findings indicate that T lymphocytes from patients with high serum IgE levels can release soluble factor(s) possessing isotype (IgE) specific potentiating activity.

B-Lymphocytes↗

Phenotypic and functional characterization of a Sézary cell.

We have studied the surface antigen pattern, enzymatic phenotype, and functional capacity of peripheral blood lymphocytes from a patient with Sézary syndrome (SS). The majority of these cells formed E rosettes but lacked the Fc(mu) receptor. The neoplastic cells were reactive with pan-T cell (OKT3)- and helper T cell (OKT4)-subset monoclonal antibodies; however, they lacked the 5/9 antigen, which identifies a more restricted subset of helper T cells. Most SS cells also reacted with PTF 29.12, a monoclonal antibody which recognizes DR determinants. Only 35% of the cells expressed single, focal accumulations of alpha-naphthyl-acid esterase activity, which is a characteristic of T.M cells, but 85% of them showed this focal staining pattern with acid phosphatase or beta-glucuronidase. Mononuclear cells from the SS patient showed poor or no proliferative response to phytohemagglutinin, pokeweed mitogen, concanavalin A, purified protein derivative, Candida, and allogeneic cells and lacked both helper and suppressor activity for pokeweed mitogen driven production of IgM and IgG immunoglobulins by normal B cells, but they were able to stimulate a marked proliferative response in mixed-lymphocyte culture. The defective expression of enzymatic and surface membrane characteristics, together with the lack of some T-cell functions, suggests that the patient cells may be immature T.M lymphocytes.

Aged↗

Effect of vitamin E deficiency on rabbit intramuscular collagen.

The effect of a vitamin E-deficient diet on muscular collagen was studied in young rabbits. Intramuscular collagen content was found to increase in vitamin E-deficient rabbits, both in absolute and relative values, while no changes in urinary hydroxyproline excretion were observed. The overall solubility of intramuscular collagen was higher and the collagen soluble in guanidine hydrochloride was richer in alpha-chains. Such findings would suggest that avitaminosis E induces the production of new intramuscular collagen.

Animals↗

Protein A reactivity of lymphocytes from some patients with chronic lymphocytic leukaemia mediated by an interaction with the F(ab')2 region of surface immunoglobulin.

Peripheral blood lymphocytes (PBL) from 15 of 38 patients with chronic lymphocytic leukaemia (CLL) were capable of forming rosettes with human erythrocytes coated with staphylococcal protein A (SpA-HRBC). PBL from seven patients also showed a marked proliferative response after stimulation with Staphylococcus aureus bacteria strain Cowan I (Cowan Staph). The SpA-rosetting of CLL cells was inhibited by incubation with F(ab')2 fragments of anti-immunoglobulin (Ig) antibodies. In addition, incubation with these fragments inhibited the proliferative response of leukaemic B cells to Cowan Staph. The Cowan-Staph induced proliferation of CLL cells was also impaired by the addition of normal human IgG and human IgG F(ab')2 fragments to the cultures, whereas non-immune rabbit IgG was not inhibitory. The inhibitory activity of human IgG F(ab')2 fragments was retained by a SpA-Sepharose column, and it was found in the material recovered from the same column by acid elution. These data indicate that an interaction between SpA and a structure located in the F(ab')2 region of surface Ig of different classes is responsible for either SpA-binding or the Cowan-Staph-induced proliferative response of PBL from some patients with CLL.

Animals↗

In vitro production of IgE by human peripheral blood mononuclear cells. III. Demonstration of a circulating IgE-bearing cell involved in the spontaneous IgE biosynthesis.

The presence of surface membrane IgE (SmIgE)-bearing cells in the peripheral blood (PB) of atopic patients was investigated by the use of isotype-specific rosettes of human red blood cells coupled to immunosorbent-purified rabbit or monoclonal mouse antibodies against human IgE (R or M anti-epsilon-HRBC). After dissociation of cell bound IgE by treatment with acid buffer, 2.1 +/- 0.3% and 1.2 +/- 0.3% circulating non-T, non-phagocytic, cells from atopic patients were still capable of forming rosettes with R or M anti-epsilon-HRBC, respectively. IgE molecules detectable on cells after dissociation of cytophilic IgE were quite resistant, like surface membrane IgM (SmIgM), to treatment with proteolytic enzymes, but they were removed under capping conditions by soluble anti-IgE antisera. All SmIgE-bearing (IgE+) cells also bore DR determinants, but many of them lacked SmIgM. Depletion of IgE+ cells strongly reduced the ability of PB lymphocyte suspensions from atopic patients to produce spontaneously IgE protein in vitro. Likewise, depletion of cells bearing DR determinants (DR+ cells) resulted in a marked decrease of the spontaneous IgE biosynthesis, whereas depletion of SmIgM-bearing (IgM+) cells had no effect. These data suggest that cells mainly implicated in the spontaneous IgE production in vitro seen in atopic patients are DR+ IgE+ IgM- circulating lymphocytes.

Antibodies, Monoclonal↗

In vitro production of IgE by human peripheral blood mononuclear cells. IV. Modulation by allergen of the spontaneous IgE antibody biosynthesis.

Peripheral blood lymphocytes (PBL) from a proportion of grass-sensitive patients, studied during or immediately after the grass pollination period, showed spontaneous production in vitro of grass-specific IgE antibody, whereas PBL from atopic patients sensitive to allergens other than grass pollens or non-atopic individuals did not. Pre-incubation of IgE antibody producing PBL from grass-sensitive patients with minute amounts of a mixed grass pollen (MGP) extract or Rye grass antigen Group I (Rye I) usually resulted in a reduction of the spontaneous production in vitro of IgE protein and in a marked inhibition of the spontaneous production in vitro of grass-specific IgE antibody. This antigen-specific inhibition was not mediated by T lymphocytes, but it was apparently due to a signal directly delivered by antigen to the spontaneously IgE antibody producing cells. The results support the concept that the activity of cells responsible for the persistent IgE antibody formation in vitro in atopic patients can be modulated by antigen.

Antibody Specificity↗

Radioimmunoassay of glipizide in human plasma.

A simple, sensitive radioimmunoassay has been developed for the direct determination of glipizide in human plasma. Antisera raised in rabbits immunized with a glipizide analogue conjugated to bovine serum albumin were highly specific, the two main metabolites, 3, cis-hydroxycyclohexyl derivative and 4,trans-hydroxycyclohexyl derivative, having cross reactivities of 0.73% and 1.66%, respectively. The method can measure amounts as small as 1 ng/ml. The intra- and inter-assay coefficients of variation lay between 2.98-5.79% and 2.35-8.66%, respectively. The mean recovery of glipizide added to plasma was 99-105% over the range 1-500 ng/ml. The method was employed to determine plasma levels in six subjects after administration of a 5 mg tablet of glipizide. The results were in accordance with those found after administration of the same dose of radiolabelled glipizide to two other subjects.

Administration, Oral↗

Bioavailability and pharmacokinetics in man of acipimox, a new antilipolytic and hypolipemic agent.

Two separate studies were performed: in the first study for healthy male volunteers received three single oral doses (150, 250 and 400 mg) of 5-methylpyrazine carboxylic acid 4-oxide (acipimox) according to a randomized sequence. Plasma levels of the drug were determined by RIA and urinary excretion by HPLC. In the second trial the effect of food on the drug bioavailability and pharmacokinetics during repeated administration was investigated in six volunteers. The RIA method was adopted to measure plasma and urine levels. Acipimox was rapidly and almost completely absorbed after the three single doses. About 90% of the administered dose was recovered as unchanges drug in urine collected up to 24 h. Peak plasma levels, area under plasma levels curves and urinary excretion were linearly related to the administered dose. The presence of food in the gastro-intestinal tract did not adversely affect the bioavailability of the drug. No significant changes were noted in the rate of elimination after 6 days of treatment with 250 mg t.i.d. Plasma levels determined after the 19th dose were in good agreement with those predicted on the assumption of linear pharmacokinetics and a one-compartment open model, with a half-life of about 2 h.

Administration, Oral↗

Surface immunoglobulins are involved in the interaction of protein A with human B cells and in the triggering of B cell proliferation induced by protein A-containing Staphylococcus aureus.

The nature of surface components responsible for the reactivity of a subset of human B cells with staphylococcal protein A (SpA) was studied. The ability of normal non-T cells or non-T cells from patients with chronic lymphocytic leukemia (CLL) to form rosettes with human red blood cells coated with SpA (SpA-HRBC) was strongly inhibited or abolished by incubation with F(ab')2 fragments of antibodies against human immunoglobulin (Ig), whereas the incubation with F(ab')2 fragments of antibodies against a non-Ig cell surface antigen, such as beta 2-microglobulin, had no effect on the SpA-rosetting of human lymphocytes. The role of the reaction between surface Ig (sIg) and SpA in the triggering of the proliferative response induced by Staphylococcus aureus bacteria strain Cowan I (Cowan Staph) on normal or leukemic non-T cells was also investigated. A parallelism was observed between the mitogenic activity on normal human non-T cells of Cowan Staph and F(ab')2 fragments of immunosorbent-purified rabbit antibodies to human mu-chain. On the other hand, monovalent Fab fragments of anti-F(ab')2 or anti-mu chain antibodies were unable to activate human non-T lymphocytes, but usually induced a partial inhibition of the Cowan Staph-induced cell proliferation. Non-T cells from 2 patients with CLL did not respond to either Fab or F(ab')2 fragments of anti-Ig antibodies, but were stimulated to proliferate by Cowan Staph. However, the proliferative response of non-T cells from these patients to Cowan Staph was markedly inhibited or abolished by the addition to the cultures of F(ab')2 fragments of anti-Ig antibodies. Antibody preparations to human F(ab')2 or gamma-chain inhibited the response of IgG-bearing leukemic cells, whereas the Cowan Staph-induced proliferation of IgM-bearing leukemic lymphocytes was inhibited by the addition to the cultures of either anti-F(ab')2 or anti-mu chain antibodies. The proliferative response to Cowan Staph or normal non-T cells was also inhibited by the addition to the cultures of human and guinea pig polyclonal IgG, whereas IgG from other species, such as goat, ox, horse, and rabbit, were poorly or not at all inhibitory. On a molar basis, the F(ab')2 preparation from human IgG was as potent an inhibitor as intact IgG molecules, whereas Fc gamma was much less effective in inhibiting the Cowan Staph-induced cell proliferation. A monoclonal IgM, isolated from the serum of a patient with CLL, whose lymphocytes were able to form rosettes with SpA-HRBC and to proliferate in vitro after stimulation with Cowan Staph, also showed a marked inhibitory activity on the Cowan Staph-induced proliferation or normal non-T cells. These data suggest that an interaction between SpA present on the bacterial cell wall and a structure located in the Fab region of sIg, which is shared by sIgM, sIgG, and perhaps also by sIg of other classes, plays an important role in the triggering of B cell proliferation induced by SpA-containing staphylococci.

Antibodies↗

Short- and long-term effects of radiation on T-cell subsets in peripheral blood of patients with Hodgkin's disease.

The present study was undertaken to determine the effect of radiotherapy on subpopulations of peripheral blood T cells from patients with Hodgkin's disease. T cell were purified from each specimen, and proportions and absolute numbers of T lymphocytes bearing receptors for the Fc portion of IgG (TG) and for Fc portion of IgM (TM) were enumerated by rosetting T cells with ox red blood cells (ORBC), which had been coated with anti-ORBC rabbit IgG or IgM, respectively. In untreated patients, the percentage of TG cells was significantly increased, and the percentage of TM cells was significantly decreased when compared with control values. In patients examined after radiotherapy, there was a severe depletion of total T lymphocytes. The percent and absolute values of TM cells were also markedly decreased in comparison with those found in either normal controls or untreated patients. In contrast, relative proportions of TG cells were significantly increased in the same treated patients, but the absolute numbers of these cells were essentially unchanged in comparison with those found before radiation therapy. There was a partial and progressive restoration of the number of TM lymphocytes some years after the treatment, but reduced percentages of TM lymphocytes and increased percentages of TG lymphocytes were still found in patients in continuous complete remission for at least five years or more. Similar alterations of the two T-cell subsets were also found in the peripheral blood of a small group of patients treated with radiation for testicular seminoma. These data clearly demonstrate that radiation therapy has a differential effect on identifiable and distinct subsets of cells in the human T-cell class.

Adult↗

Inhibition of lipolysis by nicotinic acid and by acipimox.

Acipimox (5-methylpyrazinecarboxylic acid 4-oxide) is a new lipolysis inhibitor that has a distant chemical relationship with nicotinic acid (NA). The tritiated compound (100 mg) is rapidly absorbed, peak plasma radioactivity being reached after 2 hr, with an almost total elimination unchanged in urine. A comparison of th antilipolytic activity of three doses of acipimox and three doses of NA showed acipimox to be 20 times as potent as NA. There was a correlation between intensity and duration of effect for acipimox, but not for NA. Plasma acipimox levels correlated with inhibition of lipolysis. In consideration of the very good subjective tolerability of acipimox at all doses tested, this drug may be suitable for control of lipolysis in hyperlipidemias.

Adult↗

Hyperproduction of IgE and T-cell dysfunction in Hodgkin's disease.

Serum IgE levels were evaluated in 119 untreated and 112 treated patients with Hodgkin's disease (HD). 38 of the nonatopic untreated patients showed significantly increased (> 300 IU/ml) IgE concentrations. No relationship could be found between increased IgE levels and depressed lymphocyte response to phytohemagglutinin (PHA) or the imbalance of TM and TG lymphocyte subsets. On the other hand, the mean level of suppressor activity elicitable from cells of untreated HD patients by concanavalin A preincubation did not differ significantly from that of healthy control subjects. In contrast, in treated patients, where there was a significant reduction in the number of circulating T lymphocytes, a further depression of the lymphocyte response to PHA, a more marked disproportion of TM and TG cell subsets and a noticeable fall in IgE concentration was found. These data suggest that increased IgE concentrations seen in untreated patients with HD are unrelated to the T-cell defects. They also suggest that hyperproduction of IgE is probably not invariably a consequence of a suppressor cell deficiency.

Cell Division↗

T-cell independence of immunoglobulin synthesis by human peripheral blood lymphocytes stimulated with SpA-containing staphylococci.

Unfractionated and T-cell depleted human peripheral blood lymphocytes (PBL) were cultured in vitro in the presence of pokeweed mitogen (PWM) and Staphylococcus aureus strain Cowan I (StaCw). After 7 days of culture, the cells were assayed for cytoplasmic immunoglobulins (Cyto-Ig) by direct staining using fluorescein-labelled F(ab')2 fragments prepared from specific antisera against human IgG F(ab')2. The amount of immunoglobulin of the IgM and IgG class released into the cell-free supernatants was also measured by radioimmunoassay. In unfractionated PBL StaCw, like PWM, was able to induce a significant increase of either the number of Cyto-Ig containing cells for the amount of IgM and IgG secreted into the supernatant. In contrast, the amount of IgM and IgG immunoglobulin released into the supernatant of T-cell depleted suspensions stimulated with PWM was significantly reduced in comparison with that of unfractionated populations, whereas it was unchanged in T-cell depleted vs unfractionated suspensions stimulated with StaCw. The addition of a few T lymphocytes restored the ability of T-cell depleted suspensions to produce Ig in the presence of PWM, whereas despite addition of high numbers of T cells no further augmentation of the Ig production induced by StaCw on T-cell depleted suspensions was observed. Cultures of umbilical cord blood lymphocytes (UCBL) stimulated with PWM did not generate Ig-producing cells, whereas UCBL stimulated with StaCw showed significant production of Ig of both IgM and IgG classes. The results indicate that T lymphocytes are probably not involved either with stimulation or with the suppression of Ig production induced by StaCw.

Adult↗

Study of some properties of the receptor for IgM on human lymphocytes.

Some properties of the receptor for IgM on human lymphocytes have been investigated. It was shown that the interaction of native IgM with the receptor present on T and B lymphocytes is not critical for its detection in the EAM-rosette assay. In fact, high values of EAM-RFC could be found on cell suspensions cultured overnight in either IgM-free or IgM-containing media. In addition, the inhibition of EAM-rosettes by human monoclonal IgM at 37 degrees C was not as effective as at 4 degrees C. Rabbit IgM showed a significantly greater ability to inhibit the binding of antigen-IgM antibody complexes than human IgM. The receptor for IgM was easily removed by handling procedures, the incubation of lymphocytes at 4 degrees C and treatment of the cells with low concentrations of trypsin or pronase. After the enzymatic treatment, a rapid resynthesis occurred, which restored the number of EAM-rosettes formed by T cells and significantly increased the number formed by B cells. The interaction between the receptor and antigen-IgM antibody complexes stopped the spontaneous shedding of the receptor at 4 degrees C. When the incubation of the cells with immune complexes was performed at 37 degrees C, a significantly different behaviour between T cells equipped with receptor for IgM and those possessing receptor for IgG was found. After the binding of EAG to the receptor for IgG, a process of rapid dissociation of rosettes occurred, whereas the incubation with EAM did not induce an irreversible loss of the receptor for IgM.

Antigen-Antibody Complex↗