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Biomedical subjects

M Alvarez-Mon

Publications and source records attributed to M Alvarez-Mon.

At least 91 records · Page 5Linked to original sources
PubMed1992

Increased spontaneous and lymphokine-conditioned IgA and IgG synthesis by B cells from alcoholic cirrhotic patients.

Immunoglobulin secretion by B lymphocytes is a complex process in which lymphokines secreted by T lymphocytes play an important regulatory role. Increased serum levels of IgA and IgG have been characteristically detected in patients with alcoholic cirrhosis. We have studied the functional alterations of T and B lymphocytes implicated in the physiopathology of this common immunoglobulin abnormality. After activation with phytohemagglutinin, purified T cells from alcoholic cirrhotic patients showed significantly enhanced secretion of B-cell differentiation factors for IgG and IgA with respect to those secreted by T cells from healthy controls (p less than 0.05). Simultaneously, normal secretion of B-cell differentiation factor for IgM was demonstrated in T lymphocytes from these patients. The pattern of secretion of the lymphokines involved in the regulation of the B-cell differentiation pathway found in alcoholic cirrhotic patients was different from that of the primary biliary cirrhotic patients studied. Purified B cells from patients with alcoholic cirrhosis secreted significantly higher amounts of IgA and IgG than did those found in healthy controls, both spontaneously (p less than 0.05) and after sequential activation with immunoglobulin ligands (Staphylococcus aureus Cowan I) and a standard B-cell differentiation factor preparation (p less than 0.05). By contrast, the IgM secretion and regulatory pathway were normal in alcoholic cirrhotic patients. These results support a physiopathological explanation for the characteristic hyperimmunoglobulinemia found in patients with alcoholic cirrhosis.

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PubMed1992

Deficient interleukin-2 responsiveness of T lymphocytes from patients with primary biliary cirrhosis.

There is increasing evidence that primary biliary cirrhosis is associated with an alteration of the immune system. Although the cause remains unknown, it has been suggested that the immune system of patients with primary biliary cirrhosis is involved in the pathogenesis of their disease. We have investigated the T-cell function in patients with primary biliary cirrhosis and have found defective phytohemagglutinin-induced T-cell mitogenesis. Likewise, their blastogenic response to CD3 monoclonal antibody was also depressed, although the DNA synthesis induced by stimulation with phorbol esters (12-O-tetradecanoil-phorbol-13-acetate) plus ionophore (ionomycin) was normal. These alterations could not be ascribed either to a decreased synthesis of interleukin-2 or to a defective expression of interleukin-2 receptor after cellular activation. Moreover, this defective proliferative response of T lymphocytes was observed even in the presence of saturating concentrations of exogenous interleukin-2. These results represent evidence of the deficiency in the interleukin-2-dependent pathway found in T lymphocytes from patients with primary biliary cirrhosis.

Cell Division↗
PubMed1992

Interleukin 2 and interferon alpha modulation of the lymphocyte non-major histocompatibility-restricted lytic activity in glioblastoma patients.

We studied the non-major histocompatibility-restricted cytotoxic activity induced by interleukin 2 (IL-2) and interferon alpha (IFN-alpha) in mononuclear cells of peripheral blood (PBMNC) from glioblastoma patients. We observed a depressed cytotoxic activity against natural killer (NK)-sensitive target cells in PBMNC from all the patients studied. Culture of these PBMNC with IFN-alpha for 5 days augmented the cytotoxic activity against NK-sensitive target cells in a small group of patients. Incubation with IL-2 for 5 days normalizes the decreased cytotoxic activity against NK-sensitive target cells of PBMNC from all the glioblastoma patients studied. When PBMNC from these patients were incubated with IL-2 for 5 days and IFN-alpha was added to the culture medium in the last 2 h of culture, an enhancement of non-major histocompatibility-restricted cytotoxic activity was observed compared with that obtained with either IL-2 or IFN-alpha alone. This improvement of the cytotoxic activity was more relevant when it was tested against NK-resistant target cells. The potential utility of the sequential use of the two cytokines in generating non-major histocompatibility cytotoxic activity in glioblastoma patients is discussed.

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PubMed1992

Impaired activity of natural killer cells in patients with acute brucellosis.

Researchers have claimed that natural killer (NK) cells are involved in the mechanisms of defense of the host against infections. We have investigated the activity of NK cells in peripheral blood mononuclear cells (PBMNC) from 12 patients for whom acute brucellar infection has been diagnosed and from 14 healthy controls. The sera of eight of the patients were also analyzed 3 months after initiation of a 45-day course of antibiotic treatment, at which time they had no evidence of relapse. PBMNC from patients with acute brucellar infection showed a significantly depressed NK cell activity (P < .01) when compared with those from healthy controls; this depressed activity was not related to a deficient number of NK cells since the numbers of CD56+ and CD16+ cells present in PBMNC were similar in patients and controls. Incubation of PBMNC from patients with acute brucellar infection with recombinant interleukin-2, but not with interferon-gamma, can correct this impaired cytotoxic activity. In treated patients, there was a significant enhancement (P < .05) and normalization of the previously defective NK cell activity. It is concluded that acute brucellar infection is associated with a deficient cytotoxic activity of NK cells that can be overcome by in vitro incubation with interleukin-2 and that reverts to normal after antibiotic treatment.

Acute Disease↗
PubMed1992

Immunomodulatory effect of interferon-alpha 2b on natural killer cells and T lymphocytes from patients with transitional cell carcinoma of the bladder.

Incubation of peripheral blood mononuclear cells (PBMNC) from patients with transitional cell carcinoma of the bladder, with interferon (IFN-alpha 2b) causes dose-dependent enhancement of natural killer (NK) and cytotoxic activity. Increased lytic activity was also observed against both NK-sensitive and NK-resistant target cells and T lymphocytes from such patients showed altered activity upon incubation with IFN-alpha 2b. Furthermore, intracavitary instillation of IFN-alpha 2b is associated with infiltration of the bladder wall by NK cells and T lymphocytes. Future work will be aimed at investigating the possible prognostic value of these results as related to the therapeutic effect of intracavitary instillation of IFN-alpha 2b.

Carcinoma, Transitional Cell↗
PubMed1992

Analysis of the effect of intravesical treatment with interferon-alpha 2b on the clinical evolution and on the in vivo function of T lymphocytes and natural killer cells in patients with superficial bladder tumors.

Following complete transurethral resection, patients with superficial transitional cell carcinoma (TCC) were treated with intravesical interferon-alpha 2b. Ex vivo analysis of peripheral blood mononuclear cells (PBMNC) both during and after the treatment period showed an enhancement of natural killer (NK) activity which fell to basal levels upon cessation of therapy. Simultaneous analysis of T-cell activity revealed a similar pattern of variation in the response to the polyclonal mitogen phytohemagglutinin. Both findings point to an alteration in systemic immunoreactivity as a result of intravesical treatment. Further work will be aimed at determining whether this is relevant to the therapeutic value of such treatment and whether prolonged treatment will maintain these effects.

Administration, Intravesical↗
PubMed1992

Functional impairment of natural killer cells in active ulcerative colitis: reversion of the defective natural killer activity by interleukin 2.

We have studied the functional characteristics and clinical importance of the natural killer (NK) cytotoxicity of peripheral blood mononuclear cells (PBMNC) from patients with ulcerative colitis. Normal NK activity was observed in PBMNC from patients with inactive disease, but a pronounced decrease was found in those with active disease. Clinical change from active to inactive disease was associated with enhancement of the depressed NK activity. The impairment of NK cytotoxicity found in patients with active disese could not be ascribed to a deficient number of NK cells as the amounts of HNK-1+, CD16+ (Leu 11), and CD11b (OKM1) cells in PBMNC were within normal ranges. This defective cytotoxic PBMNC activity was normalised by short term (18 hour) incubation with recombinant interleukin 2 (rIL-2). Moreover, long term (5 day) incubation of these effector cells with rIL-2 induced strong cytotoxic activity against NK resistant and NK sensitive target cells in patients with active and inactive disease. We also found that both precursors and effectors of cytotoxic activity promoted by short term and long term incubation with rIL-2 of PBMNC from the patients showed the phenotype of NK cells (CD16+, CD3-). Taken together, these results show that active ulcerative colitis is associated with a defective function of NK cells that is found to be normal in the inactive stage of the disease. The possible pathogenic and therapeutic implications of these findings are discussed.

Acute Disease↗
PubMed1991

Modulation by interferon alpha of the decreased natural killer activity in patients with glioblastoma.

It is known that natural killer (NK) cells are involved in immunosurveillance against tumours. This study examines the NK activity of mononuclear cells (MNC) from the peripheral blood of patients with glioblastoma. The cytotoxic inducer effect of interferon-alpha (IFN-alpha) upon these MNC has also been studied. A marked decrease in NK activity mediated by MNC from these patients was found. This functional defected in MNC is not due to a decrease in phenotypically defined NK cells. After long-term (5-day) incubation with IFN-alpha, MNC from 5 out of 14 patients showed strong lytic activity against NK-sensitive target cells. In this system, IFN-alpha failed to induce cytotoxic activity against NK-resistant target cells in MNC from all the patients studied. This in vitro induction of cytotoxic activity in MNC from some patients with glioblastoma by IFN-alpha suggests a potential immunotherapeutic use of the lymphokine in these subjects.

Brain Neoplasms↗
PubMed1991

Two different maturational stages of natural killer lymphocytes in human newborn infants.

The objective of this study was to assess the basis for the diminished natural killer (NK) lymphocyte activity of neonates. We found either severely reduced (63% of 68 neonates) or normal (similar to healthy adult) levels of NK activity. The percentages of cord blood mononuclear cells from the two groups of infants that expressed CD16, a differentiation antigen found in NK cells, were similar and within the range found in peripheral blood mononuclear cells of adults. However, infants with low NK activity had reduced numbers of cells in the CD16+56+ subpopulation, whereas the number of these effector cells present in cord blood mononuclear cells from infants with normal NK activity was within the range found in adults. Recombinant interleukin-2, but not recombinant interferon-gamma, normalized the low NK activity of infants in a dose- and time-dependent manner. Analysis of the pattern of target cell susceptibility to lysis, together with the CD16+CD3- phenotype of the precursor and effector lymphocytes, demonstrated that the induced cytotoxicity was mediated by NK cells. In contrast, NK cells from infants with normal cytotoxic levels exhibited a functional response to interleukin-2 and interferon-gamma similar to that of adults. Our results indicate that NK cells in human neonates go through two different maturational stages.

Adult↗
PubMed1991

Pregnancy is associated with a reduction in the pattern of the cytotoxic activity displayed by lymphokine-activated killer cells.

Several modifications in the homeostasis of the maternal immune system have been implicated in the survival of the fetoplacental graft. We have investigated the adaptive response of the cytotoxic nonmajor histocompatibility complex (MHC)-restricted effector lymphocytes in pregnancy, and have found that the spontaneous lytic activity against both natural killer (NK)-sensitive and NK-resistant target cells is either decreased or lacking in peripheral blood mononuclear cells (PBMNC) from pregnant women. Recombinant interleukin-2 (rIL-2) normalizes the cytotoxic activity of PBMNC from pregnant women against NK-sensitive target cells in a dose- and time-dependent manner, without modification in the normal amounts of HNK-1+, CD16+ (Leu 11, or CD11b+ (OKM-1) present in these effector populations. However, the pattern of lytic activity against NK-resistant target cells found in PBMNC from pregnant women after short- and long-term incubation with rIL-2 was reduced in comparison with that observed in PBMNC from nongravid women in similar conditions. Moreover, rIL-2 incubation of PBMNC from pregnant subjects was not associated with an enhancement of the lytic binding against NK-resistant target cells. These findings demonstrate that pregnancy is not only associated with a reduction in the NK lytic activity of PBMNC, but also with a reduction in the generation of lymphokine-activated killer activity, in terms of the pattern of lytic activity developed.

Cells, Cultured↗
PubMed1991

Keyhole limpet hemocyanine can enhance the natural killer activity of patients with transitional cell carcinoma of the bladder.

It has been shown that natural killer (NK) cells are involved in the immunosurveillance of tumors. In patients with transitional cell carcinoma (TCC) of the bladder, there is a negative correlation between the levels of NK activity in peripheral blood mononuclear cells (PBMNCs) and both the clinical evolution and the pathological stages of the disease. We have investigated the immunoregulatory effect of keyhole limpet hemocyanin (KLH) on the NK activity of patients with TCC of the bladder. We found that KLH enhances the cytotoxic activity of PBMNC from patients with superficial TCC against NK-sensitive target cells in a time-dependent manner. This KLH-enhanced cytotoxicity is not directed against NK-resistant target cells. However, KLH fails to normalize the depressed NK activity of PBMNCs from patients with infiltrative TCC. The present in vitro studies suggest that this immunoregulatory effect of KLH on NK cytotoxicity may be implicated in its therapeutic effect on superficial TCC of the bladder.

Adjuvants, Immunologic↗
PubMed1990

Clinical significance of natural killer activity in patients with transitional cell carcinoma of the bladder.

We studied the relationship of natural killer activity from peripheral blood mononuclear cells with clinical stage of disease and the different modalities of treatment in 67 untreated patients with transitional cell carcinoma of the bladder and 29 normal controls. Peripheral blood mononuclear cells from 39 patients with superficial bladder tumor (stages Ta and T1) showed a natural killer cell activity similar to that of controls (p greater than 0.05), while in 28 patients with infiltrating tumors (stages T2, T3 and T4) this activity was significantly depressed (p less than 0.01). This functional phenomenon cannot be ascribed to a deficient number of natural killer cells in patients with infiltrating tumors, since the amounts of HNK-1+ (Leu 7), CD16+ (Leu 11) and CD11b+ (OKM1) cells in peripheral blood mononuclear cells were similar in the 3 groups of subjects (p greater than 0.05). Furthermore, the natural killer activity of peripheral blood mononuclear cells was normal (p greater than 0.05) in patients who underwent transurethral resection of the tumors and intracavitary cytostatic therapy with doxorubicin who remained free of disease at least 6 months after treatment. However, in patients with superficial recurrent tumor a significant decrease in the natural killer activity of peripheral blood mononuclear cells was observed (p less than 0.05), which was more pronounced in those with infiltrating recurrence. Also, in the latter patients total cystoprostatectomy was associated with a relevant increase in the spontaneous level of peripheral blood mononuclear cells. We conclude that in patients with transitional cell carcinoma of the bladder there is a correlation of the levels of natural killer activity in peripheral blood mononuclear cells with clinical evolution and pathological stage of disease. The determination of this activity is useful to monitor patients with transitional cell carcinoma of the bladder.

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