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M L Villa

Publications and source records attributed to M L Villa.

At least 73 records · Page 4Linked to original sources
PubMed1988

[Graft versus host reaction and hybrid resistance in experimental models and clinical practice].

The "F1 hybrid transplantation law" states that F1 hybrids of two unrelated inbred strains of mice accept grafts from either parent strain while neither parent accept grafts from the F1 hybrid. However, there are two notable exceptions to this law. Indeed, parent grafts containing immunologically competent cells (spleen cells, bone marrow etc.) react against the F1 normal hosts in which they are placed. In the absence of a host-versus-graft reaction, the graft-versus-host reaction (GvH) may dominate the field and cause untoward reactions which not only negate any benefit derived from the graft, but also cause significant, and often fatal morbidity of the host, that is, a GvH Disease (GvHD). Furthermore, irradiated F1 mice are refractory to the grafting of parental bone marrow, lymphoma cells and normal lymphocytes because of a restriction by non-co-dominant, besides that of codominant MHC-H2 genes. These non-co-dominant genes have been designated Hh genes for Hybrid histocompatibility and the phenomenon itself, hybrid resistance. The cellular, humoral and genetic mechanisms involved in the GvH and hybrid resistance production are explained and discussed in the first, while in the second section of the present review, their equivalent in three human pathological situations are taken into consideration. We focus in detail on two principal immunologic aspects of human bone marrow transplantation: GvH and hematopoietic engraftment; each one of these immunologic aspects has considerable impact on the course and outcome of marrow transplantation in humans. The allograft implantation between HLA-genetically-identical siblings, HLA-aploidentical family members or HLA-phenotypically identical donor-recipient couples are herewith examined, while the autologous bone marrow rescue approach is not taken into consideration. The outcome of bone marrow transplantation depends not only on the degree of genetic disparity between the donor and the recipient, but also on the underlying disease. Bone marrow transplantation is the therapy of choice for patients with aplastic anemia, severe combined immunodeficiency (SCID) and other genetic and acquired immunodeficiency, some leukemias and a few other diseases, mainly if HLA-genetically-identical siblings are available. However, in many cases such siblings are not available. Therefore, the probability of acute or chronic GvHD or graft rejection increases significantly. The clinical and pathologic manifestations, the prognostic factors, and the treatment and prevention of acute and chronic GvHD are illustrated in detail.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1988

Modulation of natural killing by cyclo- and lipo-oxygenase inhibitors.

The effect on NK activity of two oxygenase inhibitors, indomethacin which is cyclo-oxygenase-specific at 10(-6) M and BW755C which blocks both cyclo- and lipo-oxygenase, has been analysed. The NK activity of human peripheral blood mononuclear cells (PBMC) has been studied in a 18-hr 51Cr-release assay. PBMC were incubated with the drugs for different periods of time before and during NK assay in order to analyse the correlations between the time of incubation and the modulation of NK activity. The results show that the inhibition of the cyclo-oxygenase alone, by indomethacin, enhances the NK activity if the drug is added both during and prior to the assay. In the latter case the enhancement is time dependent, reaching a maximum level after 18 hr of incubation. The simultaneous inhibition of lipo- and cyclo-oxygenase by BW755C has a rather more complex effect. The NK activity is similar to that of untreated cells after 6 hr incubation with BW755C, but is inhibited or greatly enhanced after 4 and 18 hr of incubation, respectively. These effects seem largely independent of the presence of monocytes because they can be observed with non-adherent PBMC (NA-PBMC).

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1987

[Antibody response in cultures of lymphocytes from patients with Hodgkin's lymphoma: role of monocytes].

In the present study we investigated the role of monocytes and of their soluble products (prostaglandins and hydrogen peroxide) in the modulation of the immune response in 50 untreated patients with Hodgkin's disease (HD) compared with a group of healthy donors. The primary response in vitro has been studied with the method of haemolytic colonies in soft agar. A defective in vitro antibody production has been observed in HD patients. Both Indomethacin addition (10(-6) M, final concentration) and depletion of plastic adherent cells, slightly increased the number of haemolytic areas in cultures from HD patients as compared with healthy donors. Similarly, the addition of catalase (8000 U/ml) which destroys H2O2, that is the main mediator of monocytes suppressor activity in normal subjects, did not restore the response of peripheral blood mononuclear cells (PBMC) from HD patients. These results suggest that monocytic cells play a minor role, if any, in the depression of the immune response in HD patients.

Adolescent↗
PubMed1986

The interference of antibiotics with antigen-specific antibody responses in man.

The effect of a series of antimicrobial drugs on human antigen-specific primary antibody response in vitro was investigated. Of the five agents tested, only streptomycin and gentamicin induced an appreciable reduction in the antibody response; penicillin G, rifampin and amikacin had a poor or irregular effect. The precise mechanisms of action of these substances on mammalian cells remain to be elucidated since an assessment of their capacity to interfere with the immune system is of particular importance in those patients with induced or acquired immunodeficiencies. In this respect, we provide an inexpensive and sensitive method for the preliminary screening of potentially immunosuppressive drugs.

Animals↗
PubMed1986

Primary in vitro antibody response in humans: role of adherent cells in the development of haemolytic colonies.

Primary antibody response in vitro by human peripheral blood mononuclear cells (PBMC) against sheep red blood cells (SRBC) was investigated by the method of haemolytic colonies in soft agar. The response was modulated by two antagonistic populations of surface-adherent cells (AC) that could be enriched by physical means using differential adhesion to the plastic. Firmly adherent cells (AC/FA), which remained surface stuck after 18 hr, cocultured with AC-depleted PBMC, significantly inhibited the production of haemolytic colonies; AC/NR cells, which were released after this interval, strongly increased the response. The inhibition by AC/FA cells was mainly due to production of peroxides and the stimulation by AC/NR to the synthesis of arachidonic acid derivatives. When the two subpopulations were present contemporarily at the concentration shown in PBMC suspensions, the suppressive action of AC/FA overwhelmed the enhancing activity of AC/NR cells. Functional, histochemical and immunochemical data suggest that the AC/FA fraction is mainly composed of typical phagocytosing cells, whereas the AC/NR fraction contains cells of uncertain classification that do not exhibit active phagocytic activity.

Adult↗
PubMed1985

Monocyte mediated modulation of the antibody response in vitro.

Human peripheral blood monocytes (PBMC) were isolated by Ficoll-Hypaque density gradient and then fractionated by differential adhesion to plastic surface. Adherent cell-depleted PBMC, non-readherent fraction and firmly adherent fraction so obtained from PBMC, PBMC themselves and a mixture of the above cells, were then sensitized in vitro with sheep erythrocytes (SRBC) so as to produce a primary antigen-dependent, antigen-specific antibody response. It appears that adherent cell-depleted PBMC produce about twice as many haemolytic areas as compared to total PBMC (from 43 to 85). If depleted PBMC are co-cultured with firmly adherent or non-readherent cells, the number of haemolytic areas goes down to 19 or up to 102, respectively. Functional, histochemical, immunochemical and morphological data suggest that the inhibiting firmly adherent fraction is composed of typical phagocytizing cells, while the enhancing cells of the non-readherent fraction are similar to the dendritic cells described in human blood and some lymphoid organs, which do not exhibit active pinocytic activity, but are the principal accessory cells needed to stimulate lymphocyte responses.

Antibody Formation↗
PubMed1985

Ultrastructural aspects of the primary in vitro antibody response of mononuclear cells in human blood.

Investigations on the morphology of cells that participate in immune responses in vitro have been limited because the recovery and identification of immunocompetent cells growing dispersely in conventional liquid cultures are technically difficult and allow only the observation of individual antibody-forming cells. Here we used a system in which focal proliferation of antisheep erythrocyte antibody-secreting cells has been induced in semisolid cultures of peripheral blood mononuclear cells. By this method, intact colonies can be observed by light microscopy at the center of each hemolytic area and then processed for electron microscopy without disrupting the connections existing among the cells. Two types of colonies develop: type I colonies which grow deeply into the agar and contain cells that undergo a complete process of differentiation from blast to mature plasma cell, and type II colonies which grow more superficially and do not seem to be directly involved in antibody production.

Antibody-Producing Cells↗
PubMed1984

[Analysis of the enzyme terminal deoxyribonucleotidyl transferase in lymphoma and leukemia cells].

This work analyses the presence of terminal deoxynucleotidyl transferase (TdT) in neoplastic lymphoid cells from a series of malignant lymphomas and in leukemic cells from blood or bone marrow of patients with lymphoproliferative diseases. The studied cases were 63 patients with acute leukemias, 26 patients with chronic leukemias, 85 patients with lymphomas and 14 normal controls. The presence of TdT in the neoplastic cells was determined by optimized assays of enzymatic activity or by immunofluorescence test for TdT positive blasts. The fluorescence tests made use of anti-TdT antibodies specifically absorbed on cells containing the enzyme and then revealed by a second fluorescent antibody. Appreciable amounts of TdT were found in the white cells of blood or bone marrow from the following 25 out of 35 acute lymphoblastic leukemias (ALL) with modulations in the different phenotypes; 13 out of 14 acute undifferentiated leukemias (AUL); and 9 out of 15 blastic crises in chronic myelogenous leukemia (CMLbc). The enzyme was present in 12 out of 14 lymphomas of lymphoblastic type (LL); 2 B lymphoblastic lymphomas did not show any TdT positivity. The highest levels of TdT were detected in cells classified as immature lymphoblast or in their precursors. TdT was absent from normal lymph nodes from leukocytes of chronic lymphocytic leukemia (CLL) and chronic (CML) and acute myelogenous leukemia (AML). 2 out of 14 cases of AML showed a border-line positivity. A definite correlation between concentrations of enzymatic activity and percentage of immunofluorescent cells could not be established. We did not find a precise correlation between the TdT content of lymphoid blasts and other clinical prognostic indices.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA Nucleotidylexotransferase↗
PubMed1983

Antigen-dependent colonies of human peripheral blood lymphocytes: an immunomorphologic study.

Human peripheral blood mononuclear cells (PBMC), stimulated by sheep red blood cells (SRBC), focally proliferate in agar and form colonies of anti-SRBC antibody-secreting cells surrounded by hemolytic areas. Two types of colonies develop: type I (diffuse type), which grows deeply into the agar, and type II (compact type), which grows above the former. Immunochemical and ultrastructural studies show that diffuse colonies contain differentiating lymphoid cells, from small lymphocytes to mature plasma cells. About 50% of cells stain positively in their cytoplasm for IgM and only 1-2% for IgG. Most colonies produce light chains of one class, whereas only a few produce both classes. Many cells resemble monocytes or T lymphocytes in their general morphology and lie in close contact with immunoglobulin-positive cells. Compact colonies contain cells not engaged in antibody production. The culture system described here is the first available antigen-dependent colony assay for human PBMC and may be useful for in vitro studies on the mechanism of human B-cell activation.

Antibody Formation↗
PubMed1983

Antibody production in cultured blood lymphocytes from breast cancer patients.

Peripheral blood lymphocytes from female patients with early breast cancer were examined before surgery for their ability to develop a primary antibody response in vitro against sheep red blood cells in soft agar cultures containing autologous plasma. After 6 days incubation, foci of proliferating hemolysin-forming cells surrounded by a lytic area were detected on the surface of the plates and counted with a dissection microscope; this response was antigen-dependent and antigen-specific. We applied this assay to a group of women suffering from early breast cancer and devoid of distant metastases. From our data, it appears that if all the patients are grouped together, cancer-bearing women produce somewhat fewer (P less than 0.05) haemolytic foci than healthy controls. However, division of the cancer patients into two subgroups, according to the TNM pretreatment clinical classification of regional lymph nodes, generated an interesting finding: N1 patients (N1b or N1a) produced definitely fewer foci than N0 patients, and the difference was highly statistically significant (P less than 0.001). The depression of anti sheep red blood cell antibody production observed in N1 patients was unrelated to the presence or absence of metastatic growth in their regional lymph nodes.

Adolescent↗
PubMed1982

Studies of terminal deoxynucleotidyl transferase in normal and neoplastic human cells.

Optimized biochemical assays and cytoimmunofluorescence tests were used to detect terminal deoxynucleotidyl transferase, TdT, in malignant cells of 36 leukemias and 75 lymphomas from patients not receiving chemotherapy. TdT was virtually absent from normal lymph nodes and from leukocytes of chronic lymphocytic leukemia, CLL, taken as controls. Its quantitative distribution in the neoplasms matched the current knowledge. Appreciable amounts of TdT were found in all the 10 lymphomas of lymphoblastic type, LL, and in the white blood cells of: 16 out of 19 acute lymphoblastic leukemia, AAL, perhaps with modulation in the various phenotypes; 2 out of 3 acute undifferentiated leukemias, AUL; and 3 out of 7 blastic crises in chronic myelogenous leukemia, b.c. CML. Biochemical and cytoimmunological analyses yielded concordant responses and even roughly comparable estimates in the same patients. TdT immunofluorescence was clearly nuclear in most cells and was cytoplasmic occasionally. Definite correlations between concentrations of enzymatic activity and percentage of immunofluorescent cells could not e established. Further detailed work will be required to identify putative subgroups in TdT-positive blast populations.

Animals↗
PubMed1981

Antibody-forming foci in soft-agar cultures of human peripheral blood cells.

Human peripheral blood lymphocytes (PBL) from healthy blood donors were grown in soft-agar gel with sheep red blood cells (SRBC) and autologous plasma as a source of complement. After 4--6 days incubation, foci of proliferating hemolysin-forming cells, surrounded by a lytic area of 0.2--0.5 mm, were detected on the surface of the plates. The response was antigen specific, since new hemolytic areas were observed on pouring a fresh agar-SRBC mixture over the surface of primary cultures, but not on pouring a mixture containing rat or rabbit erythrocytes. The antibody response was significantly increased by addition to the cultures of polyethylene glycol 6000 (PEG), 8% final concentration. The mean number of foci was 8.4 +/- 2.2 in cultures without PEG and 36.2 +/- 2.3 in PEG+ cultures, both containing 9 X 10(6) lymphocytes. This finding is in agreement with observations on the frequency of precursors of antibody-forming cells among lymphoid populations. The explanation of the mechanism by which PEG 6000 modified the immune reactivity of PBL is not clear. However, we think, that this technique provides a reliable methodology for PBL antigenic stimulation in vitro.

Agar↗
PubMed1981

[Natural killer activity in patients with malignant melanoma].

Thirty-three malignant melanoma patients were tested for NK cytotoxicity of peripheral blood lymphocytes in a Cr-release assay. NK activity was significantly lower in patients as compared with controls. In eight patients no cytotoxicity whatsoever could be detected. We tried to understand this NK impairment by using further assays such as the removal of plastic adherent cells or of carbonyl-iron phagocytizing cells and by mixing experiments. Only three patients showed the presence of NK activity suppressing cells and one patient had suppressive factors in his serum. No correlation was seen between NK activity values and clinical-biological parameters such as thickness of tumor, stage of disease, rate of recurrences or hystological findings.

Adult↗
PubMed1980

Residual heteroantigenicity of glutaraldehyde-treated porcine cardiac valves.

Treatment of porcine valves in vitro with glutaraldehyde significantly decreases their heteroantigenicity, as judged by immune reaction in mice heterografted with glutaraldehyde-treated valves or injected intraperitoneally with valvular homogenates. Conditioned porcine valves, grafted in a cutaneous pouch onto the backs of two different inbred strains (C57Bl and DBA) behave like inert material and show minimal cellular infiltration at histological examination. Little or no antibody response, demonstrate with the cytotoxicity test is elicited by glutaraldehyde-treated valvular tissue, either grafted or injected intraperitoneally as homogenate. These data supply a biological basis for the surgical practice of heterotransplants of glutaraldehyde-treated valves as an alternative to the artificial prostheses.

Aldehydes↗
PubMed1980

[Cyclic AMP levels of peripheral lymphocytes in normal subjects and in patients with malignant neoplasms].

Cellular cAMP was determined by the competitive protein binding assay (RIA method) in peripheral blood lymphocytes (PBL) isolated from 34 healthy blood donors and 31 tumor bearing patients. cAMP concentration in PBL from the cancerous patients was lower than the one found in healthy blood donors. Results are discussed in relation to the modification of immune reactivity induced by cancer.

Breast Neoplasms↗