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Biomedical subjects

M C Alonso

Publications and source records attributed to M C Alonso.

At least 73 records · Page 4Linked to original sources

Differential expression of HLA-DR and HLA-DQ antigens on normal cells of the myelomonocytic lineage.

We have previously shown that HLA-class II antigens have a differential expression on acute myeloblastic leukaemia (AML) blasts. These cells express HLA-DR molecules but the HLA-DQ antigens are undetectable. In this paper we study the expression of HLA-DR and HLA-DQ antigens, using monoclonal antibodies (MoAbs), on normal cells of the myelomonocytic lineage: the common myelomonocytic progenitor (CFU-GM) and the monocytes, by techniques of inhibition of CFU-GM growth and double immunofluoroscence, respectively. The results show that HLA-DR and HLA-DQ antigens are differentially expressed on normal myelomonocytic cells. While HLA-DR molecules are expressed on CFU-GM and on the majority of peripheral blood monocytes, HLA-DQ antigens are not expressed on CFU-GM and only present on a subpopulation of monocytes. This data further confirms that HLA-DR and HLA-DQ molecules are coded by different genes with independent regulation of the gene expression not only on myeloid leukaemias but also on normal cells of the myelomonocytic lineage.

Adult↗

Effect of exogen pentagastrin on mastocyte degranulation, gastric cAMP and intragastric pH in Shay rats.

The degranulation of mastocytes, gastric cAMP and intragastric pH after the administration of 125 micrograms/kg exogen pentagastrin in Shay rats was studied. The results showed a decrease in the number of mastocytes in the gastric mucous membrane in the first hour analysed with a highly significant increase afterwards. There was a significant increase in the values of cAMP which corresponded to an acidification of intragastric pH. From these results it may be deduced that the increase in the release of histamine, as reflected by the decrease in the number of mastocytes, provokes the increase in the gastric levels of cAMP, which would in turn be responsible for the increase in the acid secretion provoked by the administration of exogen pentagastrin.

Animals↗

Alterations in CFU-GM growth in preleukaemic and leukaemic AKR/J mice.

The behaviour of committed CFU-GM bone marrow cells was investigated in leukaemic and preleukaemic AKR/J mice. The number of bone marrow CFU-GM decreased in the leukaemic stage of spontaneous AKR/J leukaemia. The addition of AKR/J leukaemic cells inhibited CFU-GM growth from normal target bone marrow. The bone marrow CFU-GM growth was also reduced in late preleukaemic AKR/J mice, whereas no modification in the CFU-GM number in early preleukaemic animals was found.

Animals↗

Effect of pyrenzepine on gastric secretion in Shay rats.

The degranulation of the gastric mastocytes, gastric cAMP levels and intragastric pH were studied in Shay rats after the intraduodenal administration of 20 mg/kg pyrenzepine chlorhydrate. There was a significant increase in the intragastric pH after the administration of this substance, reaching its maximum alkalization 120 min later. The cAMP levels decreased significantly and reached their lowest levels 60 min later. The possible antihistaminic effect of the drug was also studied. Pyrenzepine did not reduce the acid secretion induced by the subcutaneous administration of different doses of histamine. The results show that the decrease in the cAMP gastric levels and in the acid secretion was not due to an antihistaminic effect of pyrenzepine chlorhydrate.

Animals↗

Effect of phorbol ester TPA on macrophage metabolic activity.

Metabolically active macrophages are known to play a role in tumor immune surveillance, not only as effector cells but also as collaborators in T cell mediated immune response. The present work reports that non-toxic concentrations of the tumor promoter TPA, stimulate the adherence of murine peritoneal macrophages after short time incubation, while TPA pretreatment for periods longer than 4 hrs suppresses phagocytosis, RNA and protein synthesis by these cells. Although inhibition of macrophage metabolic activity could play an additional role in tumor promotion, the enhancing and depressing effects of TPA on the immune system must be weighed before it can be assumed that TPA acts in vivo primarily to depress the immune system.

Animals↗

Depressed lymphoproliferative response in mixed leukocyte reaction after Mis-locus alloimmunization.

The proliferation of BALB/C lymphocytes preimmunized with Mis or H-2 incompatible cells in response to alloantigens was studied. The results show that preimmunization with Mis-incompatible spleen cells inhibits the lymphoproliferative response against alloantigens whereas preimmunization with H-2 incompatible spleen cells enhances it. It is suggested that Mis coded determinants activate suppressor mechanisms responsible for the unresponsiveness of these preimmunized lymphocytes against alloantigens.

Animals↗

Soluble suppressor of T cell proliferation in primary in vitro response to murine minor histocompatibility antigens.

Normal mouse lymphocytes are not capable of mounting a primary cytotoxic T cell response to Mls encoded, non H-2, allodeterminants, although a strong lymphoproliferative response is observed in primary MLR between Mls incompatible cells. In this study it is reported that in the supernatant of primary cultures between AKR macrophages and CBA/H lymphocytes (H-2 identical, incompatible for Mls and other minor antigens) a suppressor of T cell proliferation in MLR is detected. By contrast, a suppressor is not detected in supernatants from primary cultures between BALB/C macrophages and CBA/H lymphocytes (H-2 incompatible, Mls identical), B10.BR macrophages and CBA/H macrophages and CBA/H lymphocytes (syngeneic) suggesting that the production of the suppressor factor occurs only when an Mls incompatibility exists. The suppressive activity of the Mls incompatible culture supernatant upon MLR between incompatible macrophages and lymphocytes is neither antigen specific nor Mls or H-2 restricted, nor is it due to an irreversible toxic effect on T lymphocytes or macrophages. The inhibition of T cell proliferation could be explained by inhibition of IL 2 production, by blocking its union to T cells or by a combination of both effects. Our findings could help explain previous observations that lymphocytes from mice preimmunized with Mls incompatible cells have a depressed proliferative response as well as depressed cytotoxicity against alloantigens.

Animals↗

Lack of in vitro colony formation in a patient with severe aplastic anemia after spontaneous autologous hematologic reconstitution.

A case of idiopathic severe aplastic anemia with spontaneous complete remission is described. Hematologic parameters normalized spontaneously 94 days after onset. However, the ability of the patient's bone marrow cells to form granulocytic-macrophagic colony-forming units (CFU-GM) or erythroid burst-forming units (BFU-E) was depressed until the 288th day, in spite of the normalization of blood counts. Incubation of the patient's bone marrow cells with antilymphocytic globulin prior to the culture experiment normalized the number of CFU-GM and BFU-E in correlated studies. Coculture of a target marrow with several concentrations of the patient's lymphocytes or serum resulted in a complete inhibition of CFU-GM. BFU-E growth was inhibited by the patient's lymphocytes, but not by serum, which rather showed burst-promoting activity. The inhibitory effect on target bone marrow persisted for 288 days, when it disappeared concomitantly with the restoration of spontaneous CFU-GM and BFU-E growth.

Anemia, Aplastic↗

Differences in GM-CSF production from mouse peripheral blood and spleen cells stimulated by different lectins.

The capacity of mouse peripheral blood and spleen mononuclear cells to produce GM-CSF or CSA, in response to the stimulation by different mitogens (PHA, PWM and ConA) was studied. Each different kind conditioned medium was tested on target bone marrow from BALB/C mice. A significant decrease in the number of CFU-GM, was observed using peripheral blood conditioned medium stimulated by PHA or ConA in comparison with spleen conditioned medium in response to identical mitogens. When PWM is used as source of GM-CSF, significant differences between spleen and blood conditioned media were not observed. The possible significance of these findings is discussed.

Animals↗

Effect of cyproheptadine on gastric secretion in rats.

The effect of cyproheptadine on serum gastrin and glucose levels and intragastric pH values in male rats was studied. A significant increase in serum gastrin (p less than 0.001) and glucose levels (p less than 0.01) was observed after administration of 4 mg/kg, i.p. of cyproheptadine. Intragastric pH experimented a slight increase (p less than 0.05), and there were no significant changes in the gastrin levels 90 minutes after administration of different doses of cyproheptadine, although the intragastric pH values changes significantly (p less than 0.001) after administration of identical cyproheptadine doses. These results suggest that cyproheptadine stimulates gastrin secretion by an unknown mechanism and that this increase is not related to the alterations observed in serum glucose nor intragastric pH.

Animals↗

[Changes in lymphoblastic transformation in preleukemic AKR/J mice].

The authors investigate the efficacy of the immune system along the AKR/J mouse life span. They employ the phytohemagglutinin (PHA)-induced lymphoblastic transformation test. The response is compared with the immune response obtained in BALB/C mice of the corresponding age. The blastic transformation was significatively lower at 15, 25 and 35 weeks in the AKR/J mouse than in the BALB/C mouse. At the age of 45 weeks the AKR/J mouse shows an increased proportion of lymphocytes in the thymus and spleen, a weight increase of these organs, and an augmented lymphoblastic transformation in response to PHA. This phenomena are not observed in the BALB/C mouse. When macrophages are removed from the lymphocytes preparation, the PHA-induced blastic transformation of lymphocytes is not produced at any age in either AKR/J or BALB/C mice strains.

Aging↗

Expression of HLA molecules on cells from fresh explants of human digestive tract cancer.

It has been recently established that there is a correlation between the lack of MHC class I gene expression on murine tumour cells and their ability to grow and metastasize. We have studied the expression of HLA-ABC and HLA-DR products on human malignant tumours from the digestive tract using monoclonal antibodies, by indirect immunofluorescence on the cell suspensions obtained from 29 freshly explanted digestive tumours. Our results show that digestive tract cancers have an heterogeneous expression of HLA class I molecules on their surface. Whereas 50% have high levels of expression of these molecules (more than 60% positive cells), 25% have a moderate level of expression (20-60% positive cells) and 25% have weak expression (less than 20% positive cells). It has been found that there is a correlation between the level of HLA class I molecule expression and the degree of histological differentiation of a tumour. The absence of MHC class I antigens on human tumour cells, detected in this study, may play a relevant role in oncogenesis, as has been established in experimental models.

Cell Differentiation↗

Modulation of the expression of HLA class II antigens by gamma interferon and phorbol ester TPA on myeloid leukaemic cell lines.

We investigated the effect of gamma interferon and phorbol ester (TPA), on the expression of HLA class II molecules of myeloid leukaemic cell lines K562, U937, KG-1, HL-60 and ML-2. Gamma interferon induced the expression of HLA-DR but not HLA-DQ on HL-60 and ML-2, increased the expression of HLA-DR and DQ on U937 and induced the expression of HLA-DQ on KG-1. TPA treatment did not affect the expression of HLA class II antigens on U937 and KG-1 and induced the expression of HLA-DR and HLA-DQ on HL-60 and ML-2. TPA treatment did not affect the HLA phenotype of K562 but gamma interferon did induce HLA class I molecules. Thus, gamma interferon cannot only increase the expression of HLA products already expressed on the cells but can also induce the de novo synthesis of these molecules on myeloid leukaemic cell lines.

Cell Line↗

MHC class I expression on human tumour cells and their susceptibility to NK lysis.

Although natural killer (NK) activity is not restricted by the major histocompatibility complex (MHC), it has been suggested that the level of expression of MHC antigens by target cells may influence their lysis by NK cells. We have studied the NK susceptibility of 20 cell lines obtained from primitive and metastatic human tumours and the K562 cell line treated with gamma-interferon, phorbol ester TPA and tumour factor NK-RIF. When the levels of MHC class I antigen expression on the human tumour cell lines and their NK susceptibility were compared, no relationship between these two parameters was observed. Furthermore the treatment of K562 with either gamma-interferon, TPA or NK-RIF decreased its NK susceptibility independently of MHC class I expression. These results indicate that the MHC class I antigen is not the only factor directly involved in NK susceptibility and suggest that other membrane structures modulated by gamma-interferon, TPA or NK-RIF may also influence NK susceptibility.

Cytotoxicity, Immunologic↗

Retrospective evaluation of toxicity in three different schedules of adjuvant chemotherapy for patients with resected colorectal cancer. TTD Spanish Cooperative Group.

Adjuvant chemotherapy has been established since 1990 as standard treatment for patients with colon cancer stage III (Dukes' C). Chemotherapeutic schemes combining 5-fluorouracil with levamisole or leucovorin have shown significant advantage over surgery alone. Adjuvant trials are being currently implemented to investigate some relevant questions, such as which is the optimal duration of chemotherapy, as well as the possible advantage of levamisol versus leucovorin schedules, and of high-dose versus low-dose leucovorin. While these trials are ongoing, a retrospective evaluation of the toxicity associated with the different chemotherapeutic schemes might be of help when choosing the most appropriate regimen for individual patients not involved in clinical trials. A total of 519 patients subjected to three different schedules of adjuvant chemotherapy between 1993 and 1996, were evaluated for toxicity according to the NCI-CTC criteria. Chemotherapeutic regimens were: 5-fluorouracil plus levamisole (5-Fu+Lev; Moertel schedule), 5-fluorouracil plus low-dose leucovorin (5-Fu+LVLD; NCCTG schedule) and 5-fluorouracil plus high-dose leucovorin (5-Fu+LVHD; IMPACT-modified schedule). 5-Fu+LVLD is significantly more toxic than the other two regimens in terms of neutropenia, mucositis and diarrhea. delay in chemotherapy and dose reduction of 5-fluorouracil were also more frequent in the 5-Fu+LVLD group. However, the percentage of prematurely discontinued treatments was significantly higher in the 5-Fu+Lev group. Information on toxicity of adjuvant chemotherapy for colon cancer may help medical oncologists to choose the most appropriate regimen for individual patients not involved in clinical trials.

Adjuvants, Immunologic↗

Changes in the expression of HLA-class II antigens on peripheral blood monocytes from aged humans.

Increased incidence of infections, cancer, monoclonal gammopathies and rheumatic diseases in aged humans has been described. Histocompatibility antigens are involved in the regulation of immune response and it has been suggested that age-related alterations in the murine immune system may be due to changes in the expression of these antigens on the immunocompetent cells. In this paper we study the expression of HLA-DR/DP and HLA-DQ antigens on monocytes from healthy human elderly donors. Results show that peripheral blood monocytes from elderly subjects express decreased levels of HLA-DR/DP antigens (61.5 + 16.3) when compared to young controls (82.5 + 8.5) and increased levels of HLA-DQ antigens (40.4 + 16.8 and 23.6 + 7.1, respectively). The abnormal levels of expression of HLA-class II molecules could be related to the altered immune functions observed in elderly people.

Aged↗