PubMed Health⌕ Search

Biomedical subjects

M Alvarez-Mon

Publications and source records attributed to M Alvarez-Mon.

At least 73 records · Page 4Linked to original sources
PubMed1995

Urinary interleukin-1 alpha levels are increased by intravesical instillation with keyhole limpet hemocyanin in patients with superficial transitional cell carcinoma of the bladder.

Intravesical instillation of keyhole limpet hemocyanin (KLH) is a possible treatment for decreasing tumor recurrence after transurethral resection (TUR) in patients with superficial transitional cell carcinoma of the bladder (stages pTa-pT1, grades 1-3). Our study confirms the theory that instillation of KLH stimulates production of cytokines, resulting in their secretion in urine. Interleukin-1 (IL-1) stimulates the immune cascade through a domino effect and is produced mainly by activated macrophages. The instillation program was started 5-7 days after TUR of primary superficial cell carcinoma. 20 mg KLH in 20 ml of 0.9% NaCl was instilled into the bladder each week for 6 consecutive weeks and then monthly for 1 year. When KLH is instilled into the bladder, IL-1 alpha is secreted in the urine. A specific enzyme-linked immunosorbent assay (ELISA) was used for analysis. The ELISA for IL-1 alpha was established in our laboratory and showed a detection limit of 5 pg/ml. This IL-1 alpha ELISA deviation amounts to 3-7% within a series of measurements, and 5-15% from series to series. In the therapy group the IL-1 alpha secretion ranged from 0 to 30,905 pg/24 h and in the control group from 0 (collection period) to 2,472 pg/4 h. IL-1 alpha production increased significantly after KLH instillation in bladder cancer patients; however, the level varied considerably from patient to patient. Maximum production was achieved within a period of 4-8 h, decreasing within 24 h. There was a striking difference between the amount of IL-1 alpha produced over the 24-hour period in the control group and that of the KLH group. 8 of 14 patients (57%) who responded to KLH therapy had higher urine IL-1 alpha levels after 6 weeks of KLH treatment than those who failed to respond within 12 months, but the levels were not of statistical significance. The secretion of IL-1 alpha in urine is the biological response of the bladder to the antigen stimulus of KLH. No IL-2 was detected in the urine samples. It remains to be determined whether no IL-2 cytokine was present, or whether the amount was smaller than the minimal detection limit required for the ELISA.

Adjuvants, Immunologic↗
PubMed1995

Impaired natural killer cytotoxicity in peripheral blood mononuclear cells in Graves' disease.

We studied the natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) in patients with Graves' disease (GD). Peripheral blood mononuclear cells from 20 untreated hyperthyroid patients with GD showed a significantly reduced NK activity against 51 Cr-labeled K562 cells (33.9 +/- 15.9%), while in 32 euthyroid patients under antithyroid drug therapy. NK activity was similar to that of controls (46.9 +/- 17.3 and 49.9 +/- 20.2%, respectively). Furthermore, normalization of thyroid function with antithyroid drugs was associated with a significant increase and normalization of NK activity during the follow-up of nine GD patients (from 29.2 +/- 17.9 to 48.1 +/- 16.5%). This phenomenon could not be ascribed to a defective number of NK cells because the amounts of CD56+ and CD16+ cells in PBMC from both hyperthyroid and euthyroid GD patients were within normal ranges. Natural killer activity of PBMC from patients with toxic multinodular goiter was similar to that of normal controls (45 +/- 12.8 to 49.9 +/- 20%). No correlation was found between natural killer activity and serum levels of free thyroxine, TSH-inhibitory immunoglobulins, thyroidal antibodies to thryoglobulin and thyroidal microsomal antigen, dose or duration of antithyroid drug therapy. Natural killer activity from both controls and GD patients was enhanced in vitro by addition of recombinant interleukin 2 (IL-2), reaching control levels in hyperthyroid patients. These abnormalities were not associated with a defective IL-2 production by T cells, nor with a decreased IL-2R expression. We conclude that in untreated Graves' disease there is a decrease in NK cell activity in PBMC, probably dependent on the autoimmune process.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[Clinical experience with the treatment of metastatic renal cell carcinoma with subcutaneous interleukin-2r (IL-2r) and interferon Alpha-2b (IFN Alfa-2b)].

This work presents our recent clinic experience in the treatment of advanced RCC with IL-2 in association to alpha IFN given subcutaneously. Fifteen patient with histologically confirmed advanced RCC and measurable lesions were entered in the study. Patients were treated in cycles of 7 weeks at a IL-2 dose of 4.8 million IU/m2 (induction phase)-2.4 million IU/m2 (maintenance phase) every 12h five days a week and alpha IFN: 6 million IU/m2 every 24h three days a week, and were afterwards evaluated for response. Responders with localized residual bulk underwent rescue surgery. Seven patient has objective response (3 complete, 2 partial and 2 stable responses). The complete responses were stable and lasted 36 m, 14 m and 8 m, and global survival was of 14.6 m (3-36 m). All patients had toxicity at various degrees but WHO grade II was not exceeded at any time. The association of IL-2 and alpha IFN 2b given subcutaneously, appears to have antitumoral activity against advanced RCC with durable responses and in a proportion similar to other associations in intravenous administration, but with lower systemic toxicity. Surgical resection of residual bulk can be beneficial in selected patient with partial response.

Adult↗
PubMed1995

[The surgical opportunity in metastatic lesions of renal-cell carcinoma after a response to adjuvant immunotherapy].

Surgical resection of primary lesions and single metastasis can be curative, but surgery, used as the only therapeutic option, is not unanimously accepted in patients with multiple metastasis and, apart from other considerations, there are no established clinical criteria to allow us to predict which patients will benefit from a metastectomy. This study evaluates four patients with advanced RCC. Three had multiple pulmonary metastasis at the time of diagnosis and one presented retroperitoneal mass at 36 months of follow-up. All patients were nephrectomized and received adjuvant immunotherapy with an association of IL-2 and 2b alpha-IFN subcutaneously, obtaining partial response of the disease after two treatment courses. Later, the patients underwent debulking surgery. Two patients are still alive and have no evidence of disease progression at 28 months and 8 months of follow-up. This data and that contrasted with other authors, suggests that surgical management would be a reasonable option in patients who have partially responded to immunotherapy, even though the selection of both candidates and surgical strategy should be considered on an individual basis.

Aged↗
PubMed1994

Interferon beta enhances the natural killer activity of patients with bladder carcinoma.

We have investigated the effect of interferon beta (INF beta) on the natural killer (NK) cytotoxic activity of peripheral blood mononuclear cells (PBMC) from patients with superficial and infiltrative transitional-cell carcinoma of the bladder (TCC) against both NK-sensitive and NK-resistant target cells. The normal NK activity found in PBMC from these patients can be significantly enhanced by short-term incubation (18 h) with INF beta (P < 0.05). The depressed NK cytotoxic activity found in PBMC from patients with infiltrative TCC can also be significantly enhanced, but not normalized, by short-term incubation with INF beta (P < 0.05). In kinetic studies we found that the maximal levels of the INF beta-promoted cytotoxic activity against NK-sensitive and against NK-resistant target cells in PBMC from TCC patients were reached after 18 h of culture. Short-term-INF beta-incubated PBMC from patients with TCC of the bladder also showed marked cytotoxic activity against NK-resistant target cells. The effector cells of the INF beta-induced cytotoxic activity in PBMC from patients with TCC were CD16+ CD3- NK cells. This cytotoxic inducer effect of INF beta synergized with that of interleukin-2. In conclusion, INF beta can enhance the NK activity of PMBC from patients with TCC of the bladder.

Carcinoma, Transitional Cell↗
PubMed1994

Increased IgM B cell differentiation lymphokine production by T lymphocytes from patients with primary biliary cirrhosis.

Hypergammaglobulinemia, mainly due to increased serum immunoglobulin M concentrations, is a common and distinctive feature of primary biliary cirrhosis. T-B cell cooperation plays a pivotal role in the regulation of immunoglobulin secretion. In this paper, the production of regulatory B lymphokines by T cells, as well as the functional response of B lymphocytes to these molecules, was investigated in patients with primary biliary cirrhosis. T cells from patients with primary biliary cirrhosis have an enhanced ability to produce lymphokines that regulate the proliferation of B cells and their differentiation to immunoglobulins G- and M-secreting cells. In contrast, the cellular production of lymphokines involved in the induction of immunoglobulin A-secreting cells was normal. Simultaneously, the proliferation and differentiation of purified B cells in response to stimulation with surface immunoglobulin ligands and lymphokines were normal. These results suggest that the elevated serum levels of immunoglobulins M and G found in patients with primary biliary cirrhosis could be ascribed to an enhanced lymphokine-mediated T-B cooperation.

Adult↗
PubMed1994

Intracavitary prophylactic treatment with interferon alpha 2b of patients with superficial bladder cancer is associated with a systemic T-cell activation.

The activation and proliferation of peripheral blood mononuclear cells (PBMNCs) are complex processes involving several surface molecules, cell secretion and response to cytokines. This paper investigates the immunomodulatory effect of prophylactic treatment with interferon alpha 2b (IFN-alpha 2b) upon the blastogenic response of PBMNCs from patients with superficial transitional cell carcinoma (STCC) of the bladder to mitogenic signals that interact with surface molecules [phytohaemagglutinin, PHA and anti-CD3 monoclonal antibodies, (MAbs)]. PBMNCs from the patients were studied prior to the transurethral resection (TUR) of the tumour, during the second month of prophylactic intravesical instillation of IFN-alpha 2b and 3 and 6 months after finishing the instillation treatment. The [3H]thymidine uptake of PBMNCs from 17 patients with STCC of the bladder after 5 days of PHA and anti-CD3 MAb stimulus was found to be significantly lower than that of healthy controls (P < 0.05). The addition of interleukin 2 (IL-2) to the culture medium did not correct this defective proliferative response to PHA and the anti-CD3 MAb. There were no significant differences between IL-2 production in PBMNCs from STCC patients after stimulation with PHA and in PBMNCs from healthy controls (P > 0.05). Patients without evidence of recurrence showed a significantly enhanced proliferative response in PBMNC to PHA and anti-CD3 MAb after intravesical prophylactic treatment with interferon-alpha 2b in the follow-up examinations 3 and 6 months after treatment (P < 0.01). However, three patients had evidence of tumour recurrence, and they showed no enhancement of the PBMNC proliferative response to these mitogens in the same examinations. In conclusion, the prophylactic intracavitary treatment of STCC with IFN-alpha 2b may induce a systemic immunomodulatory effect which is associated to the clinical evolution of the disease.

Aged↗
PubMed1994

T lymphocyte activation in Graves' disease.

We examined the proliferative response of T lymphocytes from thirty-eight patients with Graves' disease (17 untreated thyrotoxic and 30 euthyroid on antithyroid medication) to phytohemagglutinin, anti-CD3 MoAb and phorbol esters, as well as the capacities of these lymphocytes to produce interleukin 2 and the density of interleukin 2 receptors and major histocompatibility class II antigens. We found that the response of T lymphocytes to phytohemagglutinin, anti-CD3 monoclonal antibody and phorbol esters from untreated thyrotoxic Graves' disease was significantly enhanced as compared to treated patients and normal controls. Interleukin 2 production by mitogen-triggered T lymphocytes in both treated and untreated patients with Graves' disease was comparable to that of the control population. Interleukin 2 receptor density was found to be normal, whereas that of human leukocyte antigen-DR was increased in both untreated and treated patients. Following lymphocyte stimulation, there was an increase in human leukocyte antigen-DR and interleukin 2 receptor expression in patients with untreated Graves' disease. Significant correlations were found between thyroid hormone concentration and the proliferative responses to the polyclonal mitogen phytohemagglutinin, anti-CD3 monoclonal antibody and phorbol esters in untreated Graves' patients. Furthermore, during the follow-up of 9 patients, attainment of normal thyroid function after antithyroid treatment was associated with a decrease in and normalization of T-proliferative responses. Our data reveal that active Graves' disease is associated with T cell activation and this is probably related to immunological dysregulation as well as to hyperthyroxinemia.

Antibodies, Monoclonal↗
PubMed1994

Deficient interleukin 2 dependent proliferation pathway in T lymphocytes from active and inactive ulcerative colitis patients.

There is increasing evidence that ulcerative colitis is associated with an abnormality of the immune system. Although the aetiology remains unknown, it has been suggested that the immune system of these patients is implicated in the pathogenesis of their disease. T cell function was investigated in ulcerative colitis patients and defective phytohaemagglutinin induced T cell mitogenesis was found. The DNA synthesis induced by stimulation with phorbol esters plus ionophore (ionomycin), however, was normal. These changes cannot be ascribed to either decreased interleukin 2 synthesis or to a defective interleukin 2 receptor expression after cellular activation. Moreover, this defective proliferative response of the T lymphocytes was observed even in the presence of saturated concentrations of exogenous interleukin 2. These results emphasise that the interleukin 2 dependent proliferation pathway is deficient in T lymphocytes from ulcerative colitis patients.

Adolescent↗
PubMed1994

T lymphocytes from alcoholic cirrhotic patients show normal interleukin-2 production but a defective proliferative response to polyclonal mitogens.

T lymphocyte proliferation is a complex process involving intra- and extracellular molecules. T cell activation was studied in T lymphocytes from patients with alcoholic cirrhosis. A defective phytohemagglutinin (PHA)-induced T cell mitogenesis was observed in 60% of these patients. Likewise, their blastogenic response to anti-CD3 was also depressed (p < 0.05). However, the DNA synthesis induced by stimulation with phorbol esters (12-O-tetradecanoil-phorbol-13-acetate) + ionomycin was normal (p > 0.05). These alterations cannot be ascribed either to decreased interleukin-2 synthesis or to a defective interleukin-2 receptor expression after cellular activation. Moreover, supplementation of the PHA-stimulated T cell cultures with saturant concentrations of recombinant interleukin-2 did not normalize the hypoproliferative response of T cells from alcoholic++ cirrhotic patients. These results provide evidence that a generalized alteration in the interactions between either mitogens or interleukin-2 and their receptors can explain the T lymphocyte-defective blastogenesis found in patients with alcoholic cirrhosis.

Antibodies↗
PubMed1993

Severe chronic autoimmune thrombocytopenic purpura is associated with an expansion of CD56+ CD3- natural killer cells subset.

Recent studies have indicated that autoimmune thrombocytopenic purpura (ATP) patients show immune system alterations that are not restricted to the B-cell compartment, but that also affect T lymphocytes. This report studies the phenotypic characteristics of natural killer (NK) cells in the peripheral blood of ATP patients, as well as their clinical significance in 33 ATP patients with active disease. Ten patients had stable disease (sustained platelet counts > 50,000/microL without the need for treatment), whereas 23 patients had therapy-dependent disease (platelet counts < 50,000/microL). A significant increase in both CD56+ CD3- NK cells and CD56+ CD3+ cytotoxic T lymphocytes was observed in peripheral blood mononuclear cells and in purified CD2+ cells from therapy-dependent ATP patients as compared with ATP patients with stable disease and healthy controls. Moreover, there were more major histocompatibility complex (MHC) class II molecules in the CD56+ CD3- cells from the therapy-dependent patients' peripheral blood preparations than there were in the stable ATP patients' and healthy controls' peripheral blood preparations. This growth in the number of CD56+ CD3- NK cells was statistically higher in patients whose disease was refractory to conventional therapy (corticosteroids and splenectomy). In addition to the CD56+ CD3- NK cells, the percentage of CD3+ T lymphocytes and their proliferative response to phytohemagglutinin (PHA) stimulation were studied in fresh CD2+ preparations from nine patients with stable disease, 22 patients with therapy-dependent disease, and 26 healthy controls. The proliferative response of CD2+ lymphocytes from both groups was similar and significantly defective with respect to that found in healthy controls. In conclusion, clinically severe ATP (therapy-dependent disease) is associated with a significant increase of CD56+ CD3- NK cells, which is particularly marked in patients whose disease is refractory to therapy.

Adolescent↗
PubMed1993

Heterogeneous proliferative effect of tumor necrosis factor-alpha and lymphotoxin on mitogen-activated B cells from B-chronic lymphocytic leukemia.

The proliferative effect of tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin on B cells from patients with B-chronic lymphocytic leukemia (B-CLL) was studied. Fresh purified B-CLL lymphocytes showed no proliferative response to either recombinant (r) TNF-alpha or r-lymphotoxin. However, after "in vitro" activation of B-CLL lymphocytes for 2 days with Staphylococcus aureus Cowan 1 (SAC), four of seven patients showed enhanced blastogenic response in the presence of either rTNF-alpha or r-lymphotoxin. We also found that the proliferative response of SAC-activated B-CLL lymphocytes to the two cytokines was independent of that found in the presence of interleukin-2. These results demonstrate that TNF-alpha and lymphotoxin can heterogeneously support the proliferation of in vitro activated B cells from B-CLL patients and may reflect the biological heterogeneity of B-CLL disease.

B-Lymphocytes↗
PubMed1993

T lymphocytes from autoimmune thrombocytopenic purpura show a defective activation and proliferation after cytoplasmic membrane and intracytoplasmic mitogenic signals.

T lymphocyte activation and proliferation are complex cellular processes involving membrane and cytoplasmatic molecules as well as the secretion and response to cytokines, mainly interleukin 2. There is increasing evidence that autoimmune thrombocytopenic purpura (ATP) is associated with an alteration of the regulation of the immune system. The blastogenic response of purified T lymphocytes to mitogens that interact with membrane molecules (phytohemaglutinin, anti-CD3 monoclonal antibody) and with intracytoplasmic protein kinase C (phorbol myristate acetate) has been investigated in 22 ATP patients and 18 healthy controls. After the signal given by the three different mitogens [3H]-thymidine uptake in T lymphocytes from ATP patients was found to be significantly decreased with respect to that found in healthy controls under similar experimental conditions (P < 0.05). Analysis of the cell cycle progression in these T lymphocytes from ATP patients, showed a significantly diminished percentage of cells in S-phase after PHA stimulation (P < 0.05). The percentage of CD3+ cells in the CD2+ lymphocyte preparations was significantly decreased in ATP patients relative to healthy controls (P < 0.05). But there was no significant correlation between this percentage and the blastogenic response to PHA in the CD2+ cellular preparations from both groups of subjects. No significant differences were found in the percentages of CD4+ and CD8+ cells. These data indicate that the impaired blastogenic response of T lymphocytes from ATP patients may be ascribed to an intrinsic defect in these T cells. This defective proliferative response of T lymphocytes from ATP patients cannot be ascribed to either defective interleukin 2 production or receptor expression which were both similar to those of healthy controls (P > 0.05). And, the presence of saturating amounts of exogenous interleukin 2 did not normalize the defective proliferative response the mitogenic signals on the part of T lymphocytes from ATP patients. We conclude that T lymphocytes from ATP patients have a defective proliferative response to membrane and intracytoplasmatic mitogenic signals.

Adolescent↗
PubMed1993

Thymostimulin enhances the natural cytotoxic activity of patients with transitional cell carcinoma of the bladder.

We have investigated the effect of thymostimulin on the major histocompatibility (MHC) unrestricted cytotoxic activity of peripheral blood mononuclear cells (PBMNC) from patients with superficial transitional cell carcinoma (TCC) of the bladder. PBMNC from patients and healthy controls were incubated in the presence of thymostimulin for varying periods of time (2 or 18 h or 5 days), and were used as effectors against 51Cr-radiolabeled natural killer (NK)-sensitive (K-562) and NK-resistant (JY) target cells in cytotoxic assays. In 6 out of 14 patients analyzed, thymostimulin enhanced the cytotoxic activity of PBMNC against NK-sensitive target cells in a dose-dependent manner. This cytotoxic inducer effect of thymostimulin was maximal after 18 h of culture. Thymostimulin failed to induce lytic activity in PBMNC from TCC patients against NK-resistant target cells. We also found that thymostimulin could synergize with interleukin-2 in inducing non-MHC restricted cytotoxic activity in PBMNC from TCC patients. In conclusion, we have demonstrated that thymostimulin can enhance the natural killer cytotoxic activity of PBMNC from patients with TCC of the bladder.

Adjuvants, Immunologic↗
PubMed1993

The clinical outcome of autoimmune thrombocytopenic purpura patients is related to their T cell immunodeficiency.

In this work we have furthered the understanding of the alterations of T lymphocytes from 29 patients with active autoimmune thrombocytopenic purpura (ATP) and the clinical significance of their lymphocytes. An increased percentage of in vivo activated (CD25+ and DR+) T lymphocytes was found in ATP patients with respect to that found in 22 healthy controls. The function of these T cells measured as the proliferative response to polyclonal mitogenic signals is heterogeneously impaired in ATP patients. T lymphocytes from 65.5% (19/29) of the ATP patients showed a decreased proliferative response to these mitogenic signals. This functional alteration is associated with a redistribution of the T cell compartment in these patients' peripheral blood since a significant decrease of CD4+ T lymphocytes was found. We have also found that the impairment of the T cell function is different in the diverse clinical situations of the disease. Those with stable, untreated disease showed a marked decrease in the T cell proliferative response to mitogens. Furthermore, those patients who did not respond either to steroids or to splenectomy showed significantly reduced T lymphocyte blastogenesis after phytohaemagglutinin (PHA) stimulation in comparison to that found in responding patients.

Adolescent↗
PubMed1993

Diminished DNA synthesis in T cells from B chronic lymphocytic leukemia after phytohemagglutinin, anti-CD3, and phorbol myristate acetate mitogenic signals.

T lymphocytes from patients with B cell chronic lymphocytic leukemia (B-CLL) exhibit defective proliferative response to plant lectins. The blastogenic response of purified T lymphocytes to signals that interact with membrane molecules (phytohemagglutinin [PHA], anti-CD3 monoclonal antibody [MAB]) and with the intracytoplasmic protein kinase C (PKC) was investigated in 22 B-CLL patients and 18 healthy controls. 3H-thymidine uptake in T lymphocytes from 14 of 22 B-CLL patients after PHA, anti-CD3, and phorbol myristate acetate (PMA) was found to be lower than in the healthy controls. This defective proliferative response was not corrected by the exogenous addition of interleukin-2 (IL-2) to the culture medium. In analyzing the cell cycle progression of these T lymphocytes from B-CLL patients, we found that the percentage of cells in S phase at 2 days of PHA stimulation was significantly decreased and that it was normalized after 5 days of culture. Defective response of T lymphocytes from B-CLL patients to polyclonal mitogens was observed in those patients with advanced disease (stages A, B, and C). However, this T cell proliferative response was normal in patients with "smoldering B-CLL." We conclude that the defective proliferative response to membrane and intracytoplasmatic mitogenic signals on T lymphocytes from a part of B-CLL patients can be ascribed to delayed activation and cell-cycle progression, and an association between the alterations in the T cell compartment of B-CLL patients and the progression of the disease may be suggested.

Aged↗