[Immunotherapy of urothelial neoplasms. Experimental and clinical implications of alpha interferon].
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Administration, Intravesical↗
Biomedical subjects
M Alvarez-Mon
Publications and source records attributed to M Alvarez-Mon.
Different HCl and pepsinogen I secretion patterns in anatomically defined gastric ulcer subsets.
Anatomically, functionally, and clinically, peptic ulcer patients are a heterogeneous group of subjects. These patients can be classified according to the anatomic localization of the niche. The functional state of the gastric mucosa was studied in 30 gastric ulcer patients, 25 duodenal ulcer patients, and 10 normal controls. The classification of the first group was based on Johnson's criteria, with the following results: 10 individuals were type I, 10 were type II, and 10 were type III. Pepsinogen I levels and gastric acid secretion were measured in all 65 subjects under basal conditions and after subcutaneous pentagastrin stimulation. Both basal and stimulated serum pepsinogen I values were significantly higher (p less than 0.05) in gastric ulcer type III patients than in the other four groups. These values in gastric ulcer type I were similar to those of the controls. Gastric ulcer type II patients showed an intermediate functional state similar to that of duodenal ulcer patients. In both gastric ulcer type II and duodenal ulcer patients, the basal and stimulated pepsinogen I levels were significantly higher (p less than 0.05) than those found in controls, whereas the basal serum gastrin levels were similar in the five groups. In conclusion, different HCl and pepsinogen I secretory patterns, with functional heterogenicity of the gastric mucosa, are shown here for the anatomically defined gastric ulcer subsets.
Adult↗
Natural killer activity in patients with breast cancer.
The clinical significance of the natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) was analyzed in 83 breast cancer patients and 24 healthy control women. Similar levels of NK cytotoxic activity against K-562 target cells were found in PBMC from either untreated or surgically treated patients with local or disseminated breast cancer and from normal controls. However, a transitory and significant decrease (p less than 0.05) of the NK activity of PBMC from breast cancer patients was found during chemotherapy. But, according to quantitative flow cytometry analysis, similar percentages of phenotypically defined NK cells (CD16+, CD11b+, HNK-1+) were found in PBMC from patients, whether prior to or during chemotherapy, and healthy controls. Our results demonstrate that in breast cancer patients, the percentage of NK cells present in PBMC and their lytic activity are independent of the clinical and pathological stage of the disease.
Adult↗
Plasmapheresis in heparin-induced thrombocytopenia and thrombosis.
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Heparin↗
Regulation of natural killer cytotoxicity by 1,25-dihydroxyvitamin D3.
The steroid hormone 1 alpha, 25-dihydroxyvitamin D3, calcitriol, is crucial in calcium homeostasis. Calcium plays a central role in T, B, and NK cell functions, and calcitriol is a known inhibitor of T cell proliferation and immunoglobulin production. We have analyzed here the immunoregulatory effects of calcitriol on NK cell function. We show that calcitriol specifically specifically inhibits, in a time- and dose-dependent fashion, the generation of cytotoxic activity from cultured CD16+ peripheral blood NK cells. It also suppresses, at similar molar concentrations (1-10 nM), interleukin 2 (IL-2) production by PHA-activated peripheral blood lymphocytes. Calcitriol does not interfere with the cytotoxic function of NK cells, whether fresh or generated in vitro, placing the inhibition at the level of NK cell activation. Interestingly enough, exogenous IL-2 can completely reverse the suppressive effect. These findings suggest that modulation of NK cell activation by control of the internal level of IL-2 may reflect an additional paracrine calcitriol-dependent circuit with immunoregulatory consequences.
Antigens, Differentiation↗
Spontaneously increased B cell growth factor and B cell differentiation factor activities in the synovial fluid of patients with rheumatoid arthritis.
The presence of factors implicated in B cell proliferation and differentiation was studied in synovial fluid (SF) from patients with rheumatoid arthritis (RA) and from patients with ankylosing spondylitis (AS) and traumatic joint injury. Culture with Staphylococcus aureus Cowan I B cell blasts showed strong B cell growth factor (BCGF) activity in the SF from patients with RA. This BCGF activity was significantly greater than that found in SF from patients with traumatic joint injury and similar to that of patients with AS. The presence of B cell differentiation factor (BCDF) for IgM(mu) in the SF from patients with RA was also demonstrated and was significantly greater than that found in SF from patients with AS and traumatic joint injury. Moreover, a significantly increased BCDF for IgG(gamma) was also found in the SF from patients with RA compared with that observed in those patients with traumatic joint injury, which, however, was similar to that of patients with AS.
Adult↗
Proliferation of B cells from chronic lymphocytic leukemia is selectively promoted by B cell growth factor.
B cell activation was studied in B cells from B cell chronic lymphocytic leukemia (B-CLL) patients. After in vitro stimulation, these B cells showed extensive proliferation in the presence of high-molecular-weight B cell growth factor (BCGF). In contrast, this effect was not observed upon addition of recombinant interleukin-2 (IL-2). In agreement, upon stimulation, B cells expressed Bac-1 antigen but failed to acquire the IL-2 receptor. These results demonstrate that the utilization of the BCGF pathway can be segregated from that of IL-2 in B cells from B-CLL patients.
B-Lymphocytes↗
[Immunobiology of materno-fetal relations].
Normal development of pregnancy requires maternal immune system tolerance towards the fetoplacental allograft. Natural Killer (NK) cells can display spontaneous lytic activity against tumoral, and poorly differentiated cells, without a prior sensitization. Moreover this cytotoxic activity is not restricted by the Major Histocompatibility Complex (MHC). We investigated the existence of modifications in the NK activity mediated by peripheral blood mononuclear cells (PBMC) from pregnant women. A significant depression was found in this activity from the first trimester to the puerperium that cannot be ascribed to a defective number of NK cells among pregnant's PBMC. However this impaired NK activity can be reconstituted in vitro by incubation of PBMC with interleukin 2 (IL 2). Pregnancy is also associated with an absence of effectors and/or precursors which mediate other cytotoxic non MHC-restricted activities after long term incubation with IL 2, the so called Lymphokine Activated Killer (LAK) cells.
Chorion↗
Interleukin-2 induces cytotoxic activity in lymphocytes from regional axillary nodes of breast cancer patients.
Natural killer (NK) cells and lymphokine-activated killer (LAK) cells have been involved in immunosurveillance against tumors. A normal NK activity was observed in peripheral blood (PB) mononuclear cells (MNC) from women with breast cancer, but a very low or absent NK cytotoxicity was found in the regional lymph node (RLN) MNC. However, strong cytotoxic activity against NK-resistant and NK-sensitive target cells can be induced in RLN MNC by long-term (5-day) incubation with recombinant interleukin-2 (rIL-2). This cytotoxic inducer effect of rIL-2, not observed with recombinant interferon gamma, was dose and time-dependent and was not associated with modifications in the low number of Leu 11+ or Leu 7+ cells present in the population. Both the lack of NK activity and the generation of rIL-2-activated killer cells can be readily demonstrated in either histologically affected or unaffected RLN. These results stress the value of the immunomodulators inducing cytotoxic activity in RLN MNC of patients with tumors, and are discussed in association with their possible therapeutical role.
Breast Neoplasms↗
Co-expression of Mac-1 and p150,95 on CD5+ B cells. Structural and functional characterization in a human chronic lymphocytic leukemia.
The leukocyte adhesion receptors (LAR) Mac-1 and p150,95 were thought to occur only on myeloid cells, but recently, mouse Ly-1+ (CD5+) B and pro-B cells were shown to bind M1/70 monoclonal antibody, an anti-Mac-1 antibody. Using immunoprecipitation, sodium dodecyl sulfate gel electrophoresis, immunofluorescence and flow cytometry, we have studied the expression of LAR in human CD5+ B cells from chronic lymphocytic leukemia (B-CLL) patients. 170,95 kDa Mac-1 and p150,95, as well as 180,95 kDa LFA-1 heterodimers are shown to be co-expressed on CD5+ mu + kappa + B cells from a patient where they retain their known function in homotypic cell-cell adhesion. Therefore, functional Mac-1 and p150,95 LAR are not restricted to myeloid cells.
Antibodies, Monoclonal↗
Decreased TcR-CD3+ T cell numbers in healthy aged humans. Evidence that T cell defects are masked by a reciprocal increase of TcR-CD3- CD2+ natural killer cells.
While there is accumulating evidence to indicate the presence of functional abnormalities in T cells from aged healthy humans, their cellular basis remains unclear. By using two-color immunofluorescence and multiparameter flow cytometry we show that (a) the number of peripheral blood antigen receptor-positive (TcR-CD3+) T cells is significantly lower in aged than in young adults; (b) the numbers of E-rosette-forming (CD2+) cells are maintained in the elderly due to a reciprocal increase in the frequency of TcR-CD3- cells, which constitute only a minor lymphocyte subpopulation in young adults, and (c) TcR-CD3-CD2+5- lymphocytes exhibit the phenotypic features of natural killer (NK) cells. By using functional assays we show the TcR-CD3-CD2+16+ lymphocytes are indeed NK cells because they are activated by and lyse NK targets. In contrast, they are unresponsive to either phytohemagglutinin or mitogenic CD2 monoclonal antibody stimulation, which in turn activates TcR-CD3+CD2+16- T cells. We conclude that the increase in TcR-CD3-CD2+ NK cells masks the T cell reduction in aged humans by normalizing CD2+ cell frequencies. However, NK cells cannot functionally substitute the thymus-derived lymphocytes they replace.
Aged↗
Significance of chromosome 8 breakpoint location in Burkitt's lymphoma: correlation with geographical origin and association with Epstein-Barr virus.
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Burkitt Lymphoma↗
The B-cell activation pathway in human systemic lupus erythematosus: imbalanced in vitro production of lymphokines and association with serum analytical findings.
Recent knowledge of B-lymphocyte physiology has clarified the role of T cell-derived lymphokines in clonal proliferation and differentiation of B-cell responses. Lymphokine production was analyzed in 19 systemic lupus erythematosus (SLE) patients and sex- and age-matched controls in relation to clinical activity and steroid treatment. When in vitro production of interleukin-2 (IL-2) and B-cell growth factor (BCGF) was tested, both activities were found to be diminished in the group of patients (P less than 0.01), while B-cell differentiation factor (BCDF) activity was higher in this group with respect to normal controls (P less than 0.01). Interestingly enough, this in vitro BCDF synthesis was positively correlated with clinical activity regardless of low-dose steroid treatment. A correlation was also found between BCDF production and the levels of IgG (r = 0.64, P less than 0.01), anti-DNA antibodies (r = 0.52, P less than 0.05), and the IgG/IgM ratio (r = 0.7, P less than 0.01) in serum. Implications of these abnormal T-lymphocyte functions in SLE with respect to in vivo B-cell function are discussed.
Adolescent↗
Secretin test and achlorhydria.
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Achlorhydria↗
Role of interleukin 2 in inducing normalization of natural killer activity in systemic lupus erythematosus.
A low natural killer (NK) activity has been well documented for lymphocytes from systemic lupus erythematosus (SLE) patients. Given the defect in interferon-gamma (IFN-gamma) and interleukin 2 (IL-2) production also reported in SLE, it seemed possible that the absence of these molecules could account for some of the defective NK activity. We have tested the NK activity present in peripheral blood mononuclear cells (PBMC) from SLE patients and its in vitro modulation by different preparations of exogenous IL-2. We have found a low NK activity for PBMC from steroid-treated SLE patients, and we report an enhancement in lytic activity after incubation with mitogen-induced, IL-2-containing supernatants obtained from human tonsils. This increase did not seem to be due to recruitment of new effectors because the numbers of cells expressing NK phenotype (Leu 7+ or Leu 11b+) did not change after the incubation, nor did the target specificity of the lysis. However, a similar degree in the improvement in cytotoxicity was not obtained by incubation with a purified preparation of IFN gamma and/or recombinant IL-2 (rIL-2). A possible role for a molecule other than these lymphokines that might influence this effect is discussed.
Cell Line↗
Study of the secretion of pepsinogen I in cirrhotic humans with and without portacaval shunt.
Thirty-nine subjects have been studied: 14 with hepatic cirrhosis who had not been subjected to surgery, 13 cirrhotic patients in whom portacaval shunt had been performed, and 12 normal controls. In all of them, we performed serum determinations of pepsinogen I, both basal and after pentagastrin stimulation, and of basal gastrin levels, as well as analyses of basal and stimulated gastric acid secretion (basal acid output and maximal acid output). The values for pepsinogen I, basal or post-stimulation, were higher (p less than 0.001) in patients with cirrhosis who had not undergone surgical shunt than in those in the control group. However, there were no statistically significant differences when these two groups were compared with the patients who had been subjected to portacaval shunt. In this last group of patients, seven had levels similar to those of the controls, and six presented higher values. Likewise, the values for gastric acid secretion were similar in the three groups of patients, and the basal gastrin level was lower (p less than 0.001) among patients with liver cirrhosis, whether or not they had undergone surgery, than among the control population. In conclusion, the functional alterations of the gastric mucosa in patients with hepatic cirrhosis are not significantly different from those found in cirrhotic patients with portacaval shunt.
Adult↗
Lymphotoxin is an important T cell-derived growth factor for human B cells.
Two different assays for B cell growth factors (BCGF) and an antibody against lymphotoxin were used to show that the presence of lymphotoxin in conditioned media derived from normal activated T cells and in a partially purified BCGF accounts for a substantial portion of their B cell growth-promoting activity. A competitive binding assay confirmed the presence of significant amounts of lymphotoxin in the partially purified BCGF. Recombinant lymphotoxin enhanced the proliferation of activated B cells and augmented B cell proliferation and immunoglobulin secretion induced by interleukin-2.
Antibody Formation↗
Inhibition of human natural killer (NK) activity by calcium channel modulators and a calmodulin antagonist.
The presence of calcium (Ca2+) in the culture medium is a requirement for the NK cytotoxic reaction. To further explore the role of Ca2+ and calmodulin (a cytoplasmic protein that mediates most of the biological effects of Ca2+) in this process, we evaluated the effects of nifedipine (a Ca2+ channel antagonist), BAY-K-8644 (a Ca2+ channel agonist), and haloperidol (an inhibitor of calmodulin) on the NK activity of human peripheral blood mononuclear cells (PBMC), and the augmentation of this activity by recombinant interleukin 2 (r-IL 2) and interferon-gamma (r-gamma-IFN). We found that all of these drugs inhibit NK activity in a dose-dependent fashion. This appears to result from interference with the programming for lysis stage of the lytic process. In contrast, the presence of these agents during the incubation of PBMC with r-IL 2 or r-gamma-IFN did not induce any change in the enhancement of NK activity. These data suggest that Ca2+ exerts its effect at the intracellular level during the NK cytotoxic process, and that the augmentation of NK activity by lymphokines is independent of the calcium-calmodulin system.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗