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Biomedical subjects

R Volpé

Publications and source records attributed to R Volpé.

At least 91 records · Page 5Linked to original sources
PubMed1987

Diabetes insipidus associated with dysplastic pancytopenia.

This case report describes a 60-year-old man who presented with a three-year history of generalized malaise, decreased libido, polyuria, and polydipsia. He had been previously investigated for pancytopenia, and found to have a hypoplastic bone marrow. A diagnosis of central diabetes insipidus was established; the patient was also found to have a number of other defects in his hypothalamic-pituitary function. Hematologic studies again revealed peripheral pancytopenia associated with a hypoplastic megaloblastic bone marrow. Computed axial and nuclear magnetic resonance tomography failed to establish the nature of the morphologic lesion in the hypothalamus. A possible relationship between the hematologic and endocrine disturbance is discussed.

Bone Marrow↗
PubMed1987

Immunomodulatory effect of the treatment of Graves' disease on antigen-specific monocyte procoagulant activity production.

The monocyte procoagulant activity (PCA) production assay has been shown to be a good parameter of cell-mediated immunity. We have studied antigen-specific PCA production in peripheral blood mononuclear cells from patients with Graves' disease to determine the effect of the treatment on the cell-mediated immune response. Peripheral blood mononuclear cells from patients with untreated or relapsed Graves' disease produced significantly greater PCA with thyroid antigen stimulation than those from normal subjects. Patients both on antithyroid drugs in the hyperthyroid state and within 3 months post-131I therapy also produced significantly larger amount of PCA than normal subjects. However, there was no significant difference in PCA production with thyroid antigen stimulation between normal subjects and patients on anti-thyroid drugs in the euthyroid state, or patients over 3 months post-131I therapy. The ratio of positive to negative PCA production in patients on anti-thyroid drugs in the euthyroid state or over 3 months post-131I therapy was significantly lower than in untreated or relapsed Graves' disease patients. Mononuclear cells from patients on propylthiouracil responded to propylthiouracil in vitro by production of PCA. Cells from normal subjects, untreated Graves' disease patients, or patients with Hashimoto's thyroiditis did not produce PCA with propylthiouracil stimulation. Mononuclear cells from patients who were on propylthiouracil for more than 3 months produced greater PCA than those on the drug for less than 3 months, suggesting sensitization of lymphocytes to propylthiouracil during the course of treatment. However, after 131I therapy, they gradually became unresponsive to propylthiouracil. This study has shown that the activity of the antigen-specific response assessed by PCA production in mononuclear cells from Graves' disease patients declined after treatment, suggesting that the treatment exerted immunomodulatory effects.

Adolescent↗
PubMed1987

Separate induction of MHC and thyroid microsomal antigen (McAg) expression on thyroid cell monolayers: enhancement of lectin-induced McAg expression by interferon-gamma.

Interferon-gamma (IFN gamma) induced the expression of the MHC class II antigens HLA-DR and -DQ on 1- to 2-week-old thyrocytes from normal thyroid tissue and thyroid tissue from patients with autoimmune thyroid disease; it also enhanced the expression of B2-microglobulin, which is associated with MHC class I molecules. However, the expression of thyroglobulin and thyroid microsomal antigen (McAg) was not detected after IFN gamma stimulation. Autologous and allogeneic peripheral blood mononuclear cells had the same ability as IFN gamma to induce antigen expression when cocultured with thyrocytes. In contrast, leucoagglutinin (LAG) induced McAg as well as HLA-DR and B2-microglobulin expression on thyrocytes, but not thyroglobulin expression. Concanavalin A and pokeweed mitogen also induced McAg expression. The time course of LAG induction of McAg was not always correlated with that of HLA-DR. Anti-IFN gamma, antiinterleukin-2 receptor, and anti-HLA-DR monoclonal antibodies inhibited LAG or peripheral blood mononuclear cell induction of HLA-DR expression, but not LAG induction of McAg expression. Anti-HLA-DR reduced the IFN gamma induction of HLA-DR. INF gamma enhanced thyrocyte McAg expression induced by LAG, especially when thyrocytes were incubated with IFN gamma for 24 h before LAG stimulation. In contrast, in the absence of LAG stimulation, IFN gamma suppressed already present spontaneous McAg expression. TSH did not induce McAg and HLA-DR expression on DR-negative thyrocytes, but enhanced weak DR expression induced by other stimulants, e.g. IFN gamma or lectins. These data suggest that in vitro induction mechanisms of MHC class I and II antigens and McAg are different; MHC antigens are induced by IFN gamma, whereas McAg is induced by lectin, probably acting on thyrocytes directly; and IFN gamma has an enhancing effect on LAG-induced thyrocyte McAg expression.

Antigens↗
PubMed1987

Induction of thyroid autoantibody production: synergistic effect of B cell mitogen combined with T cell mitogen.

In vitro production of thyroglobulin autoantibodies (TgAb) and thyroid microsomal autoantibodies (McAb) by peripheral blood mononuclear cells (PBMC) stimulated with the B cell mitogen Staphylococcus aureus Cowan I (SAC) and the T cell mitogen pokeweed mitogen (PWM) was examined in 35 normal subjects (NC) and 64 patients with autoimmune thyroid disease (AITD) using an enzyme-linked immunosorbent assay technique. Low concentrations of SAC plus PWM resulted in a synergistic effect on thyroid autoantibody production as well as nonspecific immunoglobulin G production. With such maximal stimulation, TgAb production was detected in all PBMC preparations from serum TgAb-positive patients with AITD; TgAb production was also detected in some NC (46%) and serum TgAb-negative patients with AITD (39%), but the levels of TgAb production were low. Similarly, McAb production was marked in PBMC preparations from serum TgAb-negative but McAb-positive patients. TgAb-secreting cells were also detected in NC by the plaque-forming cell (PFC) assay. The response patterns of PBMC to mitogen (Nil, PWM, and SAC plus PWM) in terms of TgAb production varied among serum TgAb-positive patients with AITD, but not among NC and serum TgAb-negative patients with AITD. Serum TgAb titers were significantly correlated with the in vitro production of TgAb by PBMC with no stimulation (r = 0.64; n = 99; P less than 0.001), with stimulation by PWM (r = 0.75), and with stimulation by SAC plus PWM (r = 0.87); the correlation coefficient increased with the efficiency of stimulation of B cell differentiation. Similar results were found for McAb production. These data suggest that 1) optimal in vitro thyroid autoantibody production occurs with B cell mitogen (SAC) acting synergistically with T cell mitogen (PWM); 2) sufficient numbers of resting B lymphocytes specific for Tg or microsomal antigens are present in some NC PBMC; 3) stages of thyroid-specific B cell differentiation in PBMC vary among serum thyroid autoantibody-positive patients with AITD; and 4) the potential of PBMC to produce thyroid autoantibodies may correlate with the capacity of thyroid-derived lymphocytes. Thus, the circulating lymphocytes may provide a useful vehicle by which sequential changes occurring at the tissue level may be examined.

Adolescent↗
PubMed1987

The decrease in non-specific suppressor T lymphocytes in female hyperthyroid Graves' disease is secondary to the hyperthyroidism.

There has recently been considerable interest generated in the significance of changes in the peripheral blood T lymphocyte subsets in patients with autoimmune thyroid disease. Previously, monoclonal antibodies that recognized T cells (Leu 1+ cells), T helper/inducer cells (Leu 3a+ cells), and T suppressor/cytotoxic cells (Leu 2a+ cells), have been used to enumerate these subsets. Using 2 new monoclonal antibodies (anti-Leu-8 and anti-Leu-15), in addition to the above 3 antibodies, and 2-colour flow cytometry, we have enumerated the total T, T helper/inducer, T suppressor/cytotoxic, T helper (Leu 3a+8-), T inducer (Leu 3a+8+), T suppressor (Leu 2a+15+), and T cytotoxic (Leu 2a+15-) cells in 22 patients with hyperthyroid Graves' disease, 38 patients with 131I-treated Graves' disease and 10 patients with Hashimoto's thyroiditis. All patients and controls were female. We found that hyperthyroid patients with Graves' disease had significantly lower T suppressor/cytotoxic cells (p less than 0.05) than did controls, and that this was mainly due to a decrease in T suppressor cells (p less than 0.01). Furthermore, patients with severe hyperthyroidism had a more significant decrease in T suppressor/cytotoxic (p less than 0.001) and T suppressor (p less than 0.001) cells, and an increase in the T helper/inducer:T suppressor/cytotoxic (p less than 0.01) and T helper:T suppressor (p less than 0.01) cell ratios. Patients who were euthyroid more than 1 year after 131I therapy for Graves' disease had normal T cell subsets and ratios, whether or not TSH receptor antibody or other thyroid auto-antibody titres were elevated. Ten females with Hashimoto's thyroiditis also had normal T cell subsets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Sensitization of T lymphocytes to thyroid antigen in autoimmune thyroid disease as demonstrated by the monocyte procoagulant activity test.

Monocyte procoagulant activity (PCA) production has been reported to have a close relation to cell-mediated immunity (CMI), and the collaboration of T lymphocytes is necessary to induce PCA. Antigen-specific sensitization of lymphocytes in patients with Graves' disease (GD) and Hashimoto's thyroiditis (HT) has been demonstrated by means of the production of cell-bound PCA by monocytes following antigen stimulation of whole peripheral blood mononuclear cells (PBM). These cells, obtained from both normal subjects and patients with autoimmune thyroid diseases, produced significant amounts of PCA with non-specific lectin, concanavalin A (Con A) stimulation; however, there was no significant difference between the two groups, suggesting that Con A stimulated T cells induced monocyte PCA nonspecifically. Peripheral mononuclear cells from patients with autoimmune thyroid diseases produced significantly greater amounts of PCA than PBM from normal subjects when stimulated with solubilized and IgG-free thyroid antigen. On the other hand, liver antigen did not induce significant amounts of PCA production in PBM from either normal subjects or patients. Significantly larger amounts of PCA were produced by PBM from patients following thyroid antigen stimulation than with liver antigen stimulation. Although monocytes were the major source of PCA, T cells were necessary to induce PCA in monocytes with thyroid antigen and Con A stimulation. Elimination of lymphocyte subsets in PBM from patients by negative selection (using monoclonal antibodies and complement) suggested that the collaboration of T lymphocytes, especially helper/inducer (T4+) T cells, was necessary to produce PCA with thyroid antigen stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Thyrocyte HLA-DR expression and interferon-gamma production in autoimmune thyroid disease.

We examined the expression of HLA-DR antigen induced by mitogen, mitogen-free supernatants from mitogen-stimulated peripheral blood mononuclear cells (PBMC), or autologous and allogeneic PBMC on thyrocytes cultured for 1-2 weeks (precultured) before the addition of the stimulant. Leucoagglutinin (LAG) and concanavalin A, but not lipopolysaccharide induced HLA-DR expression on thyrocytes from normal subjects (NC) and patients with Graves' disease (GD) and Hashimoto's thyroiditis (HT). The degree of DR expression induced by LAG was significantly less in GD than in NC thyrocytes. This response was dependent on contaminating T cells, especially suppressor-cytotoxic T (Ts/c) cells, NK cells, and HLA-DR+ cells, but not helper-inducer T (Th/i) cells or B cells, in the thyrocyte cultures. OKT3 monoclonal antibody, which activates T cells specifically in the presence of monocytes, also induced thyrocyte HLA-DR expression. Furthermore, interferon-gamma (IFN-gamma) was detected in culture supernatants from LAG-stimulated thyrocytes. Anti-IFN-gamma monoclonal antibody eliminated the ability of LAG to induce HLA-DR. Mitogen-free supernatants from mitogen-stimulated PBMC also induced thyrocyte HLA-DR expression, which was inhibited by anti-IFN-gamma. The supernatants of concanavalin A- or LAG-stimulated PBMC from either untreated or recently treated patients with GD or hypothyroid HT induced less thyrocyte DR expression than NC PBMC. Indeed, the levels of IFN-gamma in supernatants from such patients were lower than those in NC, and the correlation between DR expression and IFN-gamma levels was significant. This IFN-gamma production by PBMC required Th/i cells, NK cells, and HLA-DR+ cells. Before the addition of autologous or allogeneic PBMC, only precultured HT thyrocytes expressed HLA-DR, whereas GD and NC thyrocytes did not. The induction or enhancement of DR expression on autologous thyrocytes by direct coculture with PBMC occurred within 8 days in GD and HT, but not in NC. There was a significant correlation between the serum titer of antithyroid microsomal antibodies and the degree of DR expression. Allogeneic normal PBMC also induced DR expression on NC and GD thyrocytes within 8 days, the effect on the latter being more pronounced than with autologous GD PBMC. Thyrocyte HLA-DR expression induced by autologous GD PBMC and allogeneic normal PBMC required monocytes. Th/i, and NK cells and was blocked by anti-IFN-gamma. However, the enhancement of thyrocyte DR expression by autologous HT PBMC did not require monocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1986

Autoimmune thyroid disease--a perspective.

Increasing evidence is accruing in favour of the view that autoimmune thyroid disease is due to an organ-specific defect in suppressor T lymphocytes that is genetically induced. While the initial evidence supporting this hypothesis was based on results with the migration inhibition factor test, subsequent investigations from our own and other laboratories have confirmed the presence of such an organ-specific suppressor T lymphocyte defect in autoimmune thyroid disease. Moreover, there is now good evidence that hyperthyroidism per se has an effect on suppressor T lymphocyte function and numbers, and this is superimposed on and is additive to the organ-specific defect while patients are hyperthyroid; this may well act as a self-perpetuating factor in continuing the disease. It has been proposed elsewhere that the expression of HLA-DR antigen on the cell membrane of the thyrocytes (possibly induced by viral infection) represents the initial inductive step in precipitating autoimmune thyroid disease in persons predisposed by virtue of having an immunoregulatory defect in the first place. However, there is now evidence that: (1) normal thyrocytes respond equally well to various stimuli in terms of DR expression when compared to Graves' or Hashimoto's thyrocytes; (2) supernatants from normal T lymphocytes will stimulate DR expression on thyrocytes at least as well as supernatants from Graves' T lymphocytes when stimulated by non-specific lectins; (3) conversely, Graves' T lymphocytes will stimulate thyroid DR expression more markedly than normal T lymphocytes when the lymphocyte-thyrocyte interaction is direct; (4) monocytes and helper T lymphocytes are essential for thyrocyte DR expression; (5) DR expression on thyrocytes does not lead to a self-perpetuating immune response. From all of these observations, it seems evident that DR expression is secondary to the primary immune assault in autoimmune thyroid disease, and is neither an initiating event, nor unique to autoimmune thyroid disease, nor a self-perpetuating phenomenon.

Autoantibodies↗
PubMed1986

In vitro regulation of antithyroglobulin synthesis by lymphocytes of patients with Hashimoto's disease by an antigen-specific "suppressor factor" derived from cultured normal human T-lymphocytes.

Suppressor factors (SF) elaborated by peripheral blood T-lymphocytes in culture from normal subjects activated by thyroglobulin as well as those from patients with Hashimoto's thyroiditis (HT), were tested for their ability to modulate antithyroglobulin synthesis by cultured HT-lymphocytes. A micro ELISA system and a micro reverse haemolytic plaque assay system were employed to detect antithyroglobulin and antithyroglobulin secreting B-lymphocytes respectively. In the latter system, the SF from normal T-lymphocytes caused suppression of thyroglobulin-specific plaque formation by HT lymphocytes while the "SF" from HT T-lymphocytes did not cause any suppression in most of the cases studied. A "SF" obtained by using liver antigen as a non-specific antigen, did not cause suppression of plaques. These results were highly significant (p less than 0.001). Although differences were seen with and without SF in the ELISA system, they were not statistically significant, likely due to a lack of sensitivity of the ELISA system as compared with the plaque assay. These observations imply that the HT-lymphocytes were deficient in thyroid antigen specific T-suppressor cell function and/or numbers to begin with and that the added normal SF afforded the signal necessary to the helper T-cells to suppress antibody synthesis by the B-lymphocytes. It is thus inferred that there is a defect in antigen-specific suppressor T-lymphocyte function in Hashimoto's thyroiditis.

Adolescent↗
PubMed1985

Studies on the immunoregulation of thyroid autoantibody production in vitro.

The spontaneous production (without mitogen or antigen) of antithyroglobulin and antimicrosomal antibodies by peripheral (PBL) and thyroid-derived lymphocytes from patients with Hashimoto's thyroiditis (HT) has been studied with particular emphasis on the regulation of this phenomenon. Based on studies of DNA and protein synthesis, kinetic studies and B/T reconstitution experiments, in most HT patients, spontaneous production by PBL is accounted for by secretion of preformed antithyroglobulin (termed Type 1 patients), whereas active production is observed in a small minority (termed Type 2). In none of 24 HT patients could active antimicrosomal antibody production by PBL be detected. Conversely, thyroid-derived lymphocytes produced both autoantibodies by an active process. Pokeweed mitogen (PWM) stimulation enhanced antibody production by PBL in the Type 1 group but not in Type 2 or thyroid-derived lymphocytes. T lymphocytes were required for antibody synthesis in both thyroid antigen-driven and peripheral PWM-driven cultures. By separating T lymphocytes into T4+ (helper) and T8+ (suppressor) subsets with monoclonal antibodies, T-cell modulation of autoantibody production in both systems was studied. In a PWM-induced system, both thyroid and peripheral T-cell subsets were capable of modulating peripheral antibody production. In the thyroid lymphocyte antigen-specific system, further addition of thyroid derived T8+ cells alone caused partial suppression of antibody production but not with peripheral T8+ cells. Of interest was the partial decrease of antibody production by the thyroid lymphocytes by added peripheral T4+ cells. The fact that the production of thyroid autoantibodies by thyroid-derived mononuclear cells (which included T suppressor, T helper and B lymphocytes) could be reduced by the addition of more suppressor T lymphocytes suggests that an antigen-specific defect in the T4+/T8+ thyroid cell balance may account for the in vivo production of these antibodies in patients with Hashimoto's thyroiditis.

Adult↗
PubMed1985

Relapse of Graves' disease 23 years after treatment with radioactive iodine (131I).

The use of radioactive iodine (131I) in the treatment of Graves' disease results frequently in hypothyroidism requiring thyroid hormone supplementation. Relapse of Graves' disease months after inadequate treatment with 131I is well-recognized. However, late relapse of Graves' disease in a patient rendered hypothyroid by 131I years after therapy has not been reported. The authors discuss a patient who had a relapse of his Graves' disease 23 yr after treatment with 131I. Over the interval the patient had been on 1-thyroxine replacement for hypothyroidism and had persistently high levels of long acting thyroid stimulator or thyroid stimulating antibody. The authors speculate that the immune nature of Graves' disease may play a role in the observed clinical response to 131I.

Adult↗
PubMed1984

Biological activity of lymphocytotoxic antibodies in Graves' disease and Hashimoto's thyroiditis.

Sera of 48 patients with Graves' disease (GD) and 23 with Hashimoto's thyroiditis (HT) were tested for lymphocytotoxic (LCT), granulocytotoxic (GCT) and monocytotoxic (MCT) activity. In GD, 12 patients (25%) had cold-reacting LCT and 13 patients (27%) had warm-reacting LCT. LCT were cytotoxic to both B and T cells but the majority of sera with cold-reacting LCT and eluates from lymphocytes were more cytotoxic to B lymphocytes. Warm-reacting LCT were directed exclusively against B cells. LCT did not correlate with peripheral lymphocyte counts, antithyroglobulin or antimicrosomal antibodies, sex, age, pregnancies, thyroid status or medication. However the mean duration of the disease was 15 months in LCT positive group and 55 months in LCT negative group (p less than 0.01). Weak GCT were found in 8 of 35 sera (23%). Six of 33 sera (18%) contained cold-reacting MCT and 9 (27%) had warm-reacting MCT. Some cytotoxins were directed against several types of cells as evidenced by cytotoxicity of eluates from lymphocytes against PMN and/or monocytes. Of 23 patients with HT, 11 (48%) had cold-reacting LCT. None had warm-reacting LCT. Sera and eluates from lymphocytes showed predominant cytotoxicity toward B cells. No correlation to the presence of antibodies, sex, age, pregnancies, thyroid status or medication was detected. Four of 23 sera had weak cold-reacting GCT, 5 had cold-reacting MCT which killed on average 31% of monocytes and 4 had weak warm-reacting MCT. Twelve of 22 sera from GD and HT had cytotoxic activity against thyroid cells (TCT). TCT correlated with LCT at p less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Report of a case of pheochromocytoma producing immunoreactive ACTH and beta-endorphin.

A 47-year old woman is presented who had a left adrenal pheochromocytoma with manifestations also indicative of ectopic ACTH syndrome. The excised adrenal gland showed both an adrenal medullary tumor and adrenal cortical hyperplasia. Immunostaining also showed the presence in the tumor of ACTH and beta endorphins. The immediate post-adrenalectomy decline of catecholamines, ACTH, cortisol and beta endorphins indicate that the adrenal itself was the source of these hormones. This patient, the thirteenth now reported in the literature, represents one form of ectopic ACTH syndrome in which the lesion is benign, and in which a successful outcome can be anticipated.

Adrenal Cortex↗