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Biomedical subjects

A Durantez

Publications and source records attributed to A Durantez.

18 recordsLinked to original sources
PubMed1995

Modulation of cellular chemoresistance in keratinocytes by activation of different oncogenes.

Response to chemotherapeutic agents in malignant tumors depends on many factors, most of which are as yet unknown. We investigated the correlation between the activation of different oncogenes and protein-kinase-C (PKC) modulation, and the cytotoxicity of some of the most widely used anti-cancer drugs. We transformed the murine keratinocyte cell line PAM 212, with different oncogenes (v-H-ras, v-myc and adenovirus E1a) and a mutant p53 suppressor gene (mp53). The cytotoxic effect of cisplatin (CDDP), doxorubicin (DOX) and vincristine (VCR), together with the concomitant action of modulators of PKC, TPA and staurosporine were evaluated by the crystal-violet method, thymidine incorporation and flow cytometry. We report that (a) the oncogene v-H-ras induces resistance to CDDP (> 50%), DOX (> 25%) and VCR (> 20%); (b) the E1a oncogene induces only resistance to VCR (> 40%) and marked sensitivity to CDDP and DOX; (c) the mp53 oncogene induces more resistance to VCR and insignificant resistance to the other drugs; and (d) activation of PKC by TPA increases the resistance to VCR and DOX in cells transformed by the v-H-ras, while it significantly increases the lethality with CDDP of the E1a-transformed cells. Staurosporine increases the cytoxicity of all the drugs, especially in the E1a-transformed keratinocytes. In the flow-cytometry analysis, the percentage of BUdR incorporation was related to sensitivity to anti-cancer drugs.

Animals↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1987

Clinical signification of natural killer activity in B-cell chronic lymphocytic leukemia.

The natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) and lymphocytes with the capacity to form stable rosettes with neuraminidase-treated sheep red blood cells (E+) was studied in 28 previously untreated patients (11 at stage 0, 10 at stage I and 7 at stages II and III, according to Rai's classification) and 7 treated patients with B-cell chronic lymphocytic leukemia (B-CLL), all of them at stage 0 according to Rai's classification after treatment, and in 15 healthy controls. The mean NK activities of PBMC and E+ lymphocytes from untreated patients were significantly decreased (p less than 0.001) when compared with those of PBMC and E+ lymphocytes, respectively, from healthy controls. However, PBMC and E+ cells from treated patients demonstrated NK activity similar to that of the corresponding cellular populations of controls (p greater than 0.05). Furthermore, there were no significant differences among the NK activities of E+ lymphocytes from untreated B-CLL patients in the different clinical stages 0, I, II and III, according to Rai's classification (p less than 0.05). These results demonstrate that the very low or undetectable levels of NK activity present in PBMC and E+ cell populations from previously untreated patients with B-CLL, regardless of the clinical stage of the disease, can be modified by systemic therapy with alkylating agents. Moreover, the NK activity of PBMC and E+ lymphocytes from some treated patients that have achieved the stage 0 according to Rai's classification after chemotherapy can be found within the range of the lytic activity shown by PBMC and E+ cells from normal donors.

Animals↗
PubMed1985

Acute leukemia of hybrid phenotype: T lymphoid and myelomonocytic markers.

Several unique phenotypical and functional characteristics were found together in a patient with acute poorly differentiated leukemia. The blast cells showed an unusual T-cell phenotype, forming spontaneous rosettes with sheep red blood cells and expressing the T11 antigen, but were negative for the other immature or mature T markers tested--Leu-1, 3A1, T3, T4, T8, T9, T10, T6, and TdT--and reacted with the monoclonal antibody OKM1 expressed by myeloid lineage cells and which is also present in natural killer (NK) cells. Furthermore, these cells were able to produce interleukin-2 (IL-2) after mitogenic stimulation and showed cytotoxic activity against K-562 target cells after incubation with an IL-2 supernatant. These features do not correspond to any known stage of the T-cell differentiation pathway and may represent the expansion of a pre-NK cell which may be poorly represented in normal tissues.

Acute Disease↗
PubMed1980

Membranous obstruction of the inferior vena cava and hepatic veins. Budd-Chiari syndrome? A treatable disease.

Three cases of membranous obstruction of the inferior vena cava (IVC) are presented. Two of them underwent transcardiac membranotomy with good results. The third patient was treated symptomatically and died from gastrointestinal hemorrhage and hepatic coma two years after the diagnosis of Budd-Chiari syndrome. At autopsy, membranes were found in the inferior vena cava and hepatic veins. Differentiation of Budd-Chiari syndrome secondary to the presence of such a membrane is essential since these patients are potentially curable by surgical treatment. Cavography visualizes the obstruction and is the procedure of choice for diagnosis of this condition. Surgical treatment with transcardiac membranotomy is effective. Some hepatic abnormalities regress after surgery. Prophylactic postoperative treatment with diuretics seems advisable in these patients to prevent congestive cardiac failure.

Adult↗
PubMed1977

Recognition by human and rabbit sera of common antigens to leukemia blast cells, peripheral blood B-lymphocytes, and monocytes.

A human serum (obtained from a multiparous and multiple-transfused patient with chronic myelogenous leukemia) and a rabbit antiserum (obtained by immunization with papain extracts from a B-lymphoblastoid cell line) showed reactivity against antigenic specificities (different from HLA) expressed on peripheral blood B-lymphocytes, unmarked lymphocytes, and monocytes. These antigenic determinants were expressed on myeloblasts and lymphoblasts from patients with acute leukemia (during the active phase of their disease) and on B-lymphoblastoid cell lines and lymphocytes from patients with chronic lymphocytic leukemia. Purified peripheral blood T-lymphocytes, mitogen (phytohemagglutinin)-activated T-lymphocytes, and lymphoblasts (with T-cell characteristics) obtained from patients with acute lymphoblastic leukemia or established lymphoblastoid cell lines lacked these antigenic specificities. Absorption experiments indicate that the antigen(s) detected on normal mononuclear cell populations, leukemia cells, and B-lymphoblastoid cell lines were either identical or highly cross-reactive.

Animals↗
PubMed1976

Leukemia-associated antigens detected by heterologous antisera.

An antiserum was produced by immunization of rabbits with the membrane fraction of a lymphoblastoid cell line, RPMI 4265. This antiserum reacted against leukemia-associated antigens on immature blast cells of 24 patients with acute leukemia (13 myeloblastic, 11 lymphoblastic). No reactivity was observed against morphologically normal blood mononuclear cells from patients in remission, cells from normal control subjects and patients with unrelated disorders, phytohemagglutinin-induced lymphoblasts, or normal bone marrow cells. Reactivity against leukemia cells was not reduced by absorption with fetal tissues. These findings were consistent with the presence of tumor-associated antigens on leukemia cells. The antigens were detectable neither during hematologic remission nor on cells from patients with unrelated diseases.

Acute Disease↗
PubMed1976

Studies of lymphocyte-dependent antibodies to leukemia-associated antigens using frozen stored leukemia target cells.

The ability of frozen stored leukemia blast cells to participate in a lymphocyte-dependent antibody assay (LDA) is demonstrated. Frozen stored acute myelogenous and lymphocytic blast cells retained antigenicity and high viability (larger than or equal to 80%). High titer LDA reactivity against frozen stored leukemic blasts was demonstrated with heterologous (rabbit) and homologous (leukemic patient) antisera. Similarly, we demonstrated the ability of frozen stored peripheral blood mononuclear cells to mediate effectively the destruction of antibody-coated leukemia blast cells stored frozen in liquid nitrogen before use. These findings will facilitate the study of LDA and antibody-dependent cellular cytotoxicity in human leukemia patients using a completely autogeneic system.

Antibodies, Neoplasm↗
PubMed1976

Budd-Chiari syndrome due to obstruction of the inferior vena cava. A report of two cases.

Two cases of Budd-Chiari syndrome caused by membranous occlusion of the proximal portion of the inferior vena cava are presented. Both were treated surgically, using the modified technique of Kimura in one case, and a resection with direct vision and extracorporeal circulation in the other. Both patients progressed well. We discuss the etiology and pathogenesis of the syndrome, the diagnostic means that can be used, and the importance of early treatment.

Adult↗
PubMed1975

Antigens shared by leukemic blast cell and lymphoblastoid cell lines detected by lymphocyte-dependent antibody.

Lymphocyte-dependent antibodies (LDA's) directed against antigenic determinants present on lymphoblastoid cell lines as well as human leukemia blast cells were demonstrated in heterologous antisera obtained by immunizing rabbits with a membrane fraction from RPMI-4265 (a lymphoblastoid cell line derived from a patient with chronic myelogenous leukemia). LDA was present at high titers against B-lymphoblastoid, myelomonocytic, and stem cell lines. The T-lymphoblastoid cell line MOLT-4, however, did not react. LDA was demonstrated against acute myelogenous as well as lymphoblastic leukemia cells. The reactivity was not directed against phytohemagglutinin-induced blastoid antigens, fetal antigens, or fetal calf serum. Absorptions with lymphoblastoid cell lines removed all LDA reactivity. Similar results were obtained by absorbing the rabbit antiserum with acute lymphoblastic and/or acute myelogeneous leukemia cells. These findings indicate the presence of cross-reactive antigens between lymphoblastoid cell lines and leukemia cells. Furthermore, cross-reactivity between acute lymphoblastic and acute myelogenous leukemia cells was demonstrated.

Absorption↗
PubMedDate not supplied

[Inhibition of expontaneous cytotoxicity and antibody dependency by rheumatoid synovial fluid].

A number of authors have pointed out a diminution of ADCC (Antibody dependent cellular cytotoxicity) in lymphocytes from peripheral blood of patients with rheumatoid arthritis (RA). It has also been found that the addition of rheumatoid serum inhibits ADCC and also spontaneous cellular cytotoxicity (SCC). This effect could be the result of blocking of effector cell receptors for the Fc fragment of IgG by anti-immunoglobulins and/or immune complexes, present in great quantities in rheumatoid serum. We investigated the effect of synovial fluid on the ADCC and SCC shown by purified suspensions of lymphocytes from healthy donors and RA patients towards chicken erythrocytes tagged with 51 Cr. The samples of synovial fluid from patients with RA or arthrosis did not influence per se the spontaneous release of 51 Cr, once their complement had been removed. Seven-eight of the rheumatoid synovial fluid (RSF) produced a significant decline (p less than 0.01) of SCC. Lymphocytes from the peripheral blood of RA patients showed a greater decline in SCC after the addition of RSF than those from healthy subjects (p less than 0.02). In 14/16 RSF and 5/7 samples of arthrosis synovial fluid (ASF) the ability to diminish ADCC significantly (P less than 0.01) was shown. RSF maintained this inhibitory effect in 1:40 and 1:80 dilutions, whereas in these conditions ASF had no effect on ADCC. RSF and ASF, before their complement was removed, showed an opposite effect, provoking an increase in cytotoxic activity, both SCC and ADCC, though in different proportions. These experiments show that RSF, like rheumatoid serum, inhibits ADCC and SCC, possibly by the same mechanism which blocks the Fc receptors by means of immune complexes, and coincides in its general lines with the recent findings of Díaz Jouanen et al. The pathogenetic implications of this phenomenon are difficult to clarify at present. Its occurrence in vivo would represent the establishment of a local block of cytotoxic effector cells (protector effect), which, on the other hand, would no longer be able to exercise their destructive action against cells responsible for the initiation and/or maintenance of articular damage (pathogenic effect). The non-participation of T cells, in these types of cytotoxicity, previously shown by other authors, accentuates the importance of thymus-independent regulatory systems in the mechanisms which maintain articular damage in RA.

Antibody-Dependent Cell Cytotoxicity↗