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Biomedical subjects

M Alvarez-Mon

Publications and source records attributed to M Alvarez-Mon.

At least 55 records · Page 3Linked to original sources
PubMed1997

The immunosenescent phenotype in mice and humans can be defined by alterations in the natural immunity reversal by immunomodulation with oral AM3.

The reactivities of monocyte/macrophages and natural killer (NK) cells (natural immunity) were evaluated following the administration of the biological response modifier AM3. The lower number of macrophages and NK cells in middle-aged mice (MAM) compared to young adult mice (YAM) were significantly elevated following AM3 treatment to equal or greater than YAM values. Both macrophage and NK cell cytotoxicity peaked at two days following AM3 treatment and remained elevated over control values for up to 8 days following a four days treatment regimen by the oral route. Of particular interest was the clinical effect of AM3 treatment in chronic bronchitis (CB) patients and various aged volunteers. In middle-aged patients with chronic bronchitis (MACBpts) AM3 treatment resulted in significant increases in the number of monocytes as well as their phagocytic and chemotactic activity. Differential NK cell cytotoxicities were observed in MACBpts compared to middle-aged healthy adults (MAHA) and young healthy adults (YHA). Cytotoxicity in YHA was 2-fold higher than MAHA and 5-fold higher than MACBpts. The depressed number of NK cells in MACBpts was reversed following the AM3 treatment to near NK cell levels in YHA. These observations help to explain how AM3 aids in the restoration of natural cellular immunity and its possible application as an adjuvant to bacterial & viral vaccines as well as in the treatment CB.

Adjuvants, Immunologic↗
PubMed1997

Abnormalities of peripheral blood T lymphocytes and natural killer cells in alcoholic hepatitis persist after a 3-month withdrawal period.

Present information about the behavior of the different lymphoid subsets in alcoholic hepatitis (AH), including cells displaying cytotoxic activity, is scanty and contradictory. The aim of this study was to gain further insight into knowledge of the immunological abnormalities involved in AH and the possible role of ethanol (EtOH) consumption in these changes. We analyzed the distribution of a wide range of peripheral blood (PB) lymphoid subsets, both during active EtOH intake and after a 3-month withdrawal period, using multiple stainings with monoclonal antibodies and flow cytometry, as well as natural killer (NK) cytotoxic activity. AH patients entering the study were selected strictly; only those undergoing their first episode of AH with no other lesions at liver biopsy were enrolled. Regarding the alcohol intake period, the most striking finding was a significant increase of the absolute number of PB T cells affecting both CD4+ and CD8+ lymphocytes. These changes were associated with a higher expression of T-cell activation antigens, such as HLA DR and CD11c. Simultaneously, a significant increase in both NK cells (CD3-/CD56+) and the cytotoxic T cells coexpressing the CD3 and the CD56 molecules together with an increased NK cytotoxic activity were observed. By contrast, the CD19+/CD5+ B-cell subset was significantly decreased. No significant changes were observed with EtOH withdrawal except in CD5+ B lymphocytes, which returned to normal values. Our results show that, in AH patients, a significant expansion of both activated T cells and NK lymphocytes occurs in the PB, which is associated with an increased NK cytotoxic activity. Interestingly these abnormalities persist during the withdrawal period.

Adult↗
PubMed1997

Alterations in tumor necrosis factor-alpha, interferon-gamma, and interleukin-6 production by natural killer cell-enriched peripheral blood mononuclear cells in chronic alcoholism: relationship with liver disease and ethanol intake.

No previous studies have been reported on human alcoholism in which the pattern of cytokine secretion by natural killer (NK) cells is explored. The goal of the present study was to evaluate the role of NK cells in the production of cytokines in patients with chronic alcoholism, analyzing at the same time the possible relationship between cytokine production and both alcoholic liver disease and ethanol (EtOH) intake. A total of 30 chronic alcoholic patients-11 without liver disease [alcoholics without liver disease (AWLD) group] and 19 diagnosed of alcoholic liver cirrhosis-were included in this study. Twenty-five age- and sex-matched healthy volunteers were analyzed as controls. Production of interferon (IFN)-gamma, tumor necrosis factor-alpha (TNF-alpha), and interleukin (IL)-6 was performed on NK-enriched peripheral blood mononuclear cells (PBMC) after stimulation with IL-2 and IFN-alpha. In AWLD patients, the production of TNF-alpha was significantly reduced, compared with normal controls, under both IFN-alpha (p < 0.01) and IL-2 (p < 0.05) stimulation. In patients with cirrhosis, TNF-alpha production by PBMC enriched in NK cells varied depending on the EtOH intake status at the moment of evaluation. Accordingly, an increased concentration of this cytokine was detected in the supernatants of cirrhotic patients and active EtOH intake, particularly after IFN-alpha stimulation (p < 0.05); whereas, in patients with at least 1 year of alcohol withdrawal, TNF-alpha levels remained within normal range. The results on the production of IL-6 and IFN-gamma in AWLD and cirrhotic patients showed that only cirrhotic patients with a prolonged EtOH withdrawal period display abnormal production. Accordingly, in this group of patients, a significantly increased release of IL-6 was observed after both IFN-alpha and IL-2 stimulation (p < 0.01 and p < 0.05, respectively). By contrast, a lower IFN-gamma production (p < 0.005) was detected with respect to the control group. Our results point to the existence of an abnormal cytokine secretion by NK cells from chronic alcoholism patients, which depend on both the existence of liver disease and the status of EtOH intake.

Adult↗
PubMed1997

[Hepatitis B virus (HBV) and the inflammatory/immune response. I. The natural environment of the antigen presentation and immunologic chaos induced by the virus].

In this paper, the authors update on the immunopathology of hepatitis B virus (HBV) infection, with special reference to the roles of inflammatory and natural immune responses (macrophages and NK cells) in the viral clearance. The role of specific immune responses being related to the influence of the environment of the antigen presentation (macrophages, NK cells, and their related cytokines IL-12 and IFN-gamma) on Th cells within the liver. The viral scape leading to chronic hepatitis B is thought to be due (a) to the suppressive actions of the virus on NK cells and IFN-gamma production (b) to the downregulation of IL-12/IL-15 production provoked by the inflammatory response (factor C3 of the complement system) on IL-12-producing macrophages: immunologic chaos.

Adult↗
PubMed1996

Defective interferon-gamma production by T-lymphocytes from patients with acute brucellosis.

The authors investigated the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) by phytohaemagglutinin (PHA)-stimulated T-lymphocytes from 21 untreated patients with acute brucellosis. PHA-stimulated T-lymphocytes from acute brucellosis patients showed normal IL-2 production but defective IFN-gamma production (brucellosis patients 531 +/- 103 pg mL-1 vs. healthy controls 1024 +/- 212 pg mL-1) after 72 h of culture. This altered pattern of IL-2 and IFN-gamma production by T-lymphocytes was observed in seven brucellosis patients whose T-lymphocytes exhibited a normal proliferative response to PHA (61 612 +/- 18 422 cpm) as well as in the 14 patients with a defective T-lymphocyte proliferative response to the PHA after 5 days of culture (19 479 +/- 4409 cpm). After antibiotic therapy, production of the two lymphokines by the PHA-stimulated T-lymphocytes from acute brucellosis patients was similar to that of T-lymphocytes from healthy control subjects. The authors conclude that PHA-stimulated T-lymphocytes from untreated patients with acute brucellosis have defective INF-gamma production but normal IL-2 production.

Acute Disease↗
PubMed1996

Hemolytic anemia in chronic large granular lymphocytic leukemia of natural killer cells: cytotoxicity of natural killer cells against autologous red cells is associated with hemolysis.

BACKGROUND: It has ben suggested that natural killer cells are effectors in some hemolytic transfusion reactions, but a direct mechanism of the destruction of red cells has not been demonstrated. CASE REPORT: Lytic activity of natural killer cells against autologous red cells was found in a patient with large granular lymphocytic leukemia of natural killer cells and hemolytic anemia, with no evidence of immune antibody or complement-mediated hemolysis. Large granular lymphocytes in the blood showed a CD2+ CD3- CD16+ CD57+ phenotype, cytotoxic activity against natural killer cell-sensitive K562 target cells, and no lytic activity against natural killer cell-resistant JY target cells. Cytotoxicity directed against red cells was quantified by a 51Cr-specific release assay with autologous and ABO-identical red cells used as target cells and the patients purified natural killer cells used as effector cells in the presence and absence of autologous serum. The cytotoxic activity of natural killer cells was directed against autologous red cells but not against allogenic red cells, and it was not enhanced by the presence of autologous serum in the medium. Clinical remission was induced by the administration of cyclophosphamide, after which no evidence of cytotoxic activity against the red cells could be found. CONCLUSION: Hemolytic anemia in the presence of a negative direct antiglobulin test can be attributed to a direct cytotoxic mechanism mediated by natural killer cells.

Aged↗
PubMed1996

Expanded CD4+CD45RO+ phenotype and defective proliferative response in T lymphocytes from patients with Crohn's disease.

BACKGROUND & AIMS: An abnormal immune response may play a pathogenic role in Crohn's disease. The aim of this study was to determine the role of regulatory T cells in Crohn's disease. METHODS: T-cell phenotype and function were studied in blood lymphocytes from patients with Crohn's disease and a control group consisting of healthy donors and patients with ulcerative colitis. RESULTS: Flow cytometric studies showed a significant increase in the percentage of CD3+DR+ and CD4+CD45RO+ T cells in patients with Crohn's disease. T cells from patients with Crohn's disease and ulcerative colitis showed a defective proliferative response after stimulation with surface mitogenic ligands (phytohemagglutinin and anti-CD28 or anti-CD3 antibodies). Soluble interleukin-2 receptor alpha was augmented in the Crohn's disease and ulcerative colitis groups. In the Crohn's disease group, impairment of T-lymphocyte proliferation was normalized by exogenous interleukin 2, although endogenous interleukin-2 production and interleukin-2 receptor alpha expression were normal. CONCLUSIONS: An in vivo expansion of CD4+ T lymphocytes with memory phenotype and impaired T-cell proliferation that can be restored by pharmacological amounts of interleukin 2 was found in patients with Crohn's disease. There is a severe immunodisturbance in the T-cell compartment of patients with either clinically active or inactive Crohn's disease.

Adult↗
PubMed1996

Distribution of peripheral blood lymphoid subsets in alcoholic liver cirrhosis: influence of ethanol intake.

The aim of the present study was to investigate the effect of chronic ethanol (EtOH) consumption on the immune system in patients with alcoholic liver cirrhosis (ALC), as analyzed by the distribution of peripheral blood (PB-) T, B, and NK lymphoid subsets using multiple stainings with monoclonal antibodies and flow cytometry. For that purpose, we have analyzed a group of patients with ALC and active EtOH intake (ALCET group) which were re-evaluated 3 months after alcohol withdrawal. As controls, both ALC patients with at least 1 year of alcohol withdrawal (ALCAW group) and healthy subjects were used. Regarding the alcohol intake period, the most relevant findings were a significant activation of the PB T-cell compartment, and specifically of the TCR alpha beta + subset, as reflected by an increased expression of both the HLA DR and CD11c antigens as well as a significant increase of both the PB NK cells (CD3-/CD56+) and the cytotoxic T cells coexpressing the CD3 and CD56 molecules. In addition, a decrease of both the numbers of total B cells and their CD5+/CD19+ subset were observed. After a relatively short withdrawal period (3 months), the abnormalities of T, P, and NK cells disappeared. These findings suggest the existence of a close relationship between EtOH consumption and the abnormalities of the immune system observed during active alcoholism. Nevertheless, ALCAW individuals displayed marked alterations on the immunophenotypic profile, as reflected by a significantly decreased number of total T cells, due to reduced levels of the CD3+/TCR alpha beta+, CD4+, CD8+, and CD4+/CD45RA+ T-cell subsets. In addition, a significantly decreased number of total PB B cells was observed in this group of patients. Our results show that in patients suffering from ALC, the abnormalities of the immune system due to a direct effect of EtOH intake (or its metabolites) should be distinguished from the immunological alterations related to the liver disease itself.

Alcohol Drinking↗
PubMed1996

Increased production of interleukin-6 by T lymphocytes from patients with multiple myeloma.

Alterations in T lymphocyte functions may affect other cellular components of the immune system. Several lymphokines produced by T cells are involved in the proliferation and differentiation of human B lymphocytes. Alterations in the secretion of these molecules may be implicated in the development of B cell lymphoproliferative diseases. We have investigated the production of interleukin-2 (IL-2) and interleukin-6 (IL-6) by T lymphocytes from 14 patients with multiple myeloma (MM) and 16 healthy controls. The phenotypical and functional characteristics of these T lymphocytes were also studied. The proliferative response to vegetal lectin phytohemagglutinin (PHA) stimulation was decreased in T lymphocytes from MM patients (p < 0.01). This defective proliferative response cannot be ascribed to either defective IL-2 production or diminished receptor expression, since neither of these parameters showed a significant difference between MM patients and healthy controls (p < 0.05). However, the defective proliferative response of T lymphocytes from MM patients was reverted by the addition of saturating amounts of exogenous IL-2 (p > 0.05) but not by exogenous IL-6 (p < 0.05). The IL-6 production by PHA-stimulated T lymphocytes from the MM patients was significantly higher than in healthy controls (p < 0.01). We conclude that T lymphocytes from MM patients show a functional alteration with a defective proliferative response to PHA that is reverted by exogenous addition of IL-2. After lectin stimulation, the production of IL-2 by T lymphocytes from those patients was normal, while IL-6 secretion was increased.

Aged↗
PubMed1995

Use of intracavitary interferon-alpha-2b in the prophylactic treatment of patients with superficial bladder cancer.

BACKGROUND: The evolution of superficial transitional cell carcinoma (TCC) of the bladder poses a clinical management problem due to its tendency to recur after initial transurethral resection (TUR). Natural Killer (NK) cells are a distinct subset of lymphocytes that possess the ability to lyse tumor cells without prior sensitization in a nonmajor histocompatibility-restricted fashion. These cytotoxic cells constitute a relevant barrier against the local growth and systemic dissemination of neoplastic diseases. METHODS: The immunomodulatory effect, after TUR of the tumor, of the prophylactic treatment with intravesical instillations of interferon-alpha-2b (IFN-alpha-2b) upon the NK activity of peripheral blood mononuclear cells (PBMNC) in 17 patients with superficial TCC of the bladder was analyzed using a 4-hour 51sodium chromate (51Cr)-release cytotoxicity assay against both NK-sensitive, or K562, and NK-resistant, or JY, tumor target cells. RESULTS: There were no significant modifications of the NK activity of PBMNC during the 3 months of IFN-alpha-2b intracavitary treatment (P > 0.05). However, with respect to their levels before treatment, NK activity in PBMNC at 3 months posttreatment was enhanced significantly in the 14 patients who showed no sign of tumor recurrence in the 12 months of follow-up (P < 0.01). Six months after finishing the intracavitary IFN-alpha-2b instillations, the PBMNC NK activity in these patients had returned to the levels found before initiating the therapy (P > 0.05). This temporary enhancement of the PBMNC NK activity was not found in three patients with evidence of tumor recurrence at some time during the 12 months after treatment. In similar experimental conditions, significant enhancement of the NK activity in PBMNC was not observed in nine patients with superficial bladder TCC who were treated with intracavitary instillations of mitomycin C (MMC) after the TUR of the tumor and who were free of recurrence of the disease at 1 year of follow up. CONCLUSION: The prophylactic intracavitary treatment of superficial bladder TCC with IFN-alpha-2b may induce an immunomodulatory effect in the NK activity of PBMNC that appears to be associated with the clinical evolution of the disease.

Administration, Intravesical↗
PubMed1995

Abnormal gamma IFN and alpha TNF secretion in purified CD2+ cells from autoimmune thrombocytopenic purpura (ATP) patients: their implication in the clinical course of the disease.

Gamma inferferon (gamma IFN), alpha tumor necrosis factor (alpha TNF), and interleukin 6 (IL-60) are cytokines produced by a wide variety of cells, including T lymphocytes and NK cells. These cytokines affect B-cell proliferation and differentiation into immunoglobulin secreting cells. In addition, gamma IFN and alpha TNF also enhance the function of macrophages, upregulating the expression of their IgG receptors. Abnormalities in the production of these cytokines may be involved in the clinical course of autoimmune thrombocytopenic purpura (ATP). This paper describes the production of these cytokines in PHA-stimulated peripheral blood CD2+ cells from ATP patients. Both gamma IFN and alpha TNF were significantly increased in PHA-stimulated CD2+ cells from therapy-dependent ATP patients (platelet counts < 50,000/microliter), as compared to ATP patients with stable disease (sustained platelet counts < 50,000/microliter without need treatment) (P < 0.05). No significant differences were found in gamma IFN production by PHA-stimulated CD2+ cells between therapy-dependent ATP patients and healthy controls (P < 0.05). However, the production of alpha TNF by PHA-stimulated CD2+ cells from therapy-dependent ATP patients was significantly higher compared to that found in healthy controls (P < 0.05). There were no significant differences in IL-6 production by PHA-stimulated CD2+ cells from ATP patients and healthy controls (P < 0.05). These findings demonstrate abnormal gamma IFN and alpha TNF secretion in purified CD2 cells from ATP patients. The clinical severity of the disease is associated with the altered secretion of these lymphokines by CD2 cells.

Adolescent↗
PubMed1995

Natural killer cell activity in patients with pernicious anemia.

Patients with pernicious anemia have an estimated risk of gastric adenocarcinoma that ranges from three- to fivefold greater than that of the general population. It has been reported that NK cells may be involved in immunosurveillance against tumor spread. The natural killer cell activity of peripheral blood mononuclear cells was analyzed in 22 patients with pernicious anemia and in 19 healthy controls. Levels of natural killer cell activity against K-562 target cells were similar in control subjects and patients, regardless of gastrin levels and time elapsed since diagnosis. According to quantitative flow cytometry analysis, similar percentages of phenotypically defined NK cells (CD16+) were found in peripheral blood mononuclear cells from patients and healthy controls. Our results show that in pernicious anemia patients, the percentage of NK cells present in peripheral blood mononuclear cells and their lytic activity are normal.

Aged↗
PubMed1995

Behaviour of zinc in physical exercise: a special reference to immunity and fatigue.

The variations in plasma zinc levels is dependent which follows intensivity of exercise. It is clear that there are short-term effects of exercise on zinc metabolism. It has also been shown that a high level of constant exercise can have long-term effects on zinc metabolism. It has been reported that runners have lower plasma zinc levels than controls. Long term endurance training has been shown to significantly decrease resting serum zinc levels in both male and female athletes compared to sedentary controls. Severe zinc deficiency can affect muscle function. One consequence of low serum zinc levels could be a reduction in muscle zinc concentrations. Since zinc is required for the activity of several enzymes in energy metabolism it could be predicted that low muscle zinc levels would result in a reduction in endurance capacity. Zinc may also be acting directly at membrane level; changes in extracellular zinc levels have been reported to influence twitch-tension relationship in muscle. Some investigators have associated acute and exhaustive exercise with decreased immune function. The mechanisms by which physical stress modulates immune competence are complex, involving both immune and neuroendocrine messengers. Muscular fatigue is of critical importance and as such it has been the subject matter of numerous investigators. Although many factors have been identified, a clear cause remains elusive. Factors discussed include: energy supply, the accumulation of metabolites, eccentric work, immune dysfunctions, etc. Recently we have demonstrated that daily high and maintained physical training over a prolonged period of time (7 mo) provokes marked modifications in the immune system of elite sportsmen accompanied by a psychological and biochemical stress level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Persistent lymphocytosis of natural killer cells in autoimmune thrombocytopenic purpura (ATP) patients after splenectomy.

We report three patients with primary autoimmune thrombocytopenic purpura (ATP) who developed an absolute lymphocytosis (lymphocyte count > 5 x 10(9)/l) after splenectomy and with a lymphocyte count between 5.4 and 8.9 x 10(9)/l. An immunophenotype study showed that the peripheral blood lymphocytosis was a persistent NK cell expansion (CD2+, CD56+, CD3-), and was characterized by a typical large granular lymphocytes (LGL) morphology. Two of these three ATP patients were refractory to splenectomy.

Aged↗
PubMed1995

Defective functional response to membrane stimuli in lymphocytes from patients with benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a local disturbance in the prostate that may involve an inflammatory infiltrate predominantly composed of activated lymphocytes and macrophages. The activation and proliferative response of T lymphocytes to different mitogenic signals has been analysed in peripheral blood mononuclear cells (PBMC) from 45 patients with BPH and 55 healthy controls. The PBMC obtained from the patients showed a significant specific impairment in proliferation, CD25 expression and IL-2 production in response to stimulation with lectins (phytohaemagglutinin (PHA), concanavalin A (Con A)), that was not corrected by the addition of IL-2 or of phorbol esters (phorbol myristate acetate (PMA)). Also, the CD28 response was defective in patient PBMC. Activation with anti-CD3 or anti-CD2 MoAbs was normal, but the addition of PMA to these stimuli provoked a significant defective response. Only the use of transmembrane stimuli (PMA and ionomycin) elicited responses similar to those found in the control group. The results indicate that peripheral T lymphocytes from BPH patients show a functional impairment that is mainly explained by an alteration of membrane signals (PHA, CD28) and is distal to protein kinase C (PKC) activation.

Aged↗
PubMed1995

Functional defect of T cells in autoimmune gastritis.

The functional response and phenotypic characterisation of peripheral blood T cells were studied in 41 patients with autoimmune gastritis--nine patients with autoimmune gastritis alone, 11 with untreated pernicious anaemia, and 21 with resolved pernicious anaemia who were taking vitamin B-12. Phenotypic analysis showed no changes in the CD4/CD8 ratio in any group of patients. CD3+ cells were significantly decreased and CD16+ cells were significantly increased in patients with autoimmune gastritis alone. Phytohaemagglutinin induced T cell proliferation, with or without interleukin 2, was reduced in the three groups. T cell proliferation induced by phorbol myristate acetate was normal. Interleukin 2 production of phytohaemagglutinin-stimulated lymphocytes was normal in the three groups. Five patients with pernicious anaemia treated with vitamin B-12 were followed and persistent hypoproliferation of T cells in response to phytohaemagglutinin was observed. The follow up study of the phenotype of these patients showed a significant increase of the CD2+ CD3- lymphocyte population after six months' treatment. In conclusion, the three groups of autoimmune gastritis patients studied have a functional defect in T cells that is independent of B-12 treatment and of the presence of pernicious anaemia.

Aged↗