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Biomedical subjects

M C Territo

Publications and source records attributed to M C Territo.

17 recordsLinked to original sources
PubMed1992

Helicobacter pylori secretes a chemotactic factor for monocytes and neutrophils.

Helicobacter pylori is associated with an inflammatory reaction in the stomach and duodenum, yet the mechanism of this inflammatory infiltrate is unknown. The ability of Helicobacter pylori to secrete a factor that attracts leucocytes is investigated. Helicobacter pylori conditioned supernatant attracted neutrophils and monocytes with 50-100% of the activity of control chemotactic factor, 10(-8) M formyl-methionine-leucine-phenylalanine. Strains derived from individuals with ulcer or non-ulcer associated H pylori infections displayed similar chemotactic activity. Preliminary characterisation shows that the factor has a molecular weight of less than 3000, is heat stable, is acid resistant, and can be diluted at least 10-fold. Checkerboard analysis confirmed that the activity was chemotactic rather than chemokinetic. This chemotactic activity could play a role in the pathogenesis of Helicobacter pylori gastritis.

Chemotactic Factors↗
PubMed1992

Bone marrow transplantation versus high-dose cytarabine-based consolidation chemotherapy for acute myelogenous leukemia in first remission.

PURPOSE: Despite substantial progress in the treatment of acute myeloid leukemia (AML), fewer than 25% of patients survive free of leukemia for more than 5 years without allogeneic bone marrow transplantation (BMT). In this study we analyzed the results of one or more cycles of high-dose cytarabine-based consolidation chemotherapy as compared with allogeneic BMT in first remission. PATIENTS AND METHODS: The results in 28 adult patients, aged 16 to 45 years, who underwent a closely HLA-matched BMT for AML in first remission were compared with those in 54 consecutive, age-matched, adult patients treated with one or more cycles of high-dose, cytarabine-based consolidation chemotherapy. RESULTS: After a median follow-up of 4 years, the actuarial risk of leukemic relapse was considerably lower in the transplant group than in the group treated with consolidation chemotherapy (32% +/- 26% v 60% +/- 14%; P = .05). Treatment-related mortality, however, was much higher in the group treated with BMT (32% v 6%, P = .002). The actuarial disease-free survival at 5 years was not significantly different for the two groups (45% +/- 24% v 38% +/- 14%). CONCLUSIONS: Our results show that BMT in first remission AML did not offer a disease-free survival advantage over intensive postremission consolidation chemotherapy. Larger studies are needed to identify patients who might benefit most from BMT.

Actuarial Analysis↗
PubMed1990

Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors by modified low-density lipoproteins.

Oxidized lipoproteins have been identified in atherosclerotic plaques and in early lesions in humans as well as in animals. There is accumulating evidence that such oxidized lipoproteins have an important role in atherosclerosis. Treatment of endothelial cells with altered lipoproteins stimulates monocyte binding as well as the production of chemotactic factors for monocytes. Both these findings could be relevant to the accumulation of monocytes-macrophages in the arterial wall during the early stages of lesion development. We now report that treatment of endothelial cells (EC) with modified low-density lipoproteins obtained by mild iron oxidation or by prolonged storage, results in a rapid and large induction of the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage CSF (M-CSF) and granulocyte CSF (G-CSF). These growth factors affect the differentiation, survival, proliferation, migration and metabolism of macrophages/granulocytes, and G-CSF and GM-CSF also affect the migration and proliferation of EC. Because EC and macrophages are important in the development of atherosclerosis, the expression of the CSFs by these cells could contribute to the disease.

Aorta↗
PubMed1990

Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells.

After exposure to low density lipoprotein (LDL) that had been minimally modified by oxidation (MM-LDL), human endothelial cells (EC) and smooth muscle cells (SMC) cultured separately or together produced 2- to 3-fold more monocyte chemotactic activity than did control cells or cells exposed to freshly isolated LDL. This increase in monocyte chemotactic activity was paralleled by increases in mRNA levels for a monocyte chemotactic protein 1 (MCP-1) that is constitutively produced by the human glioma U-105MG cell line. Antibody that had been prepared against cultured baboon smooth muscle cell chemotactic factor (anti-SMCF) did not inhibit monocyte migration induced by the potent bacterial chemotactic factor f-Met-Leu-Phe. However, anti-SMCF completely inhibited the monocyte chemotactic activity found in the media of U-105MG cells, EC, and SMC before and after exposure to MM-LDL. Moreover, monocyte migration into the subendothelial space of a coculture of EC and SMC that had been exposed to MM-LDL was completely inhibited by anti-SMCF. Anti-SMCF specifically immunoprecipitated 10-kDa and 12.5-kDa proteins from EC. Incorporation of [35S]methionine into the immunoprecipitated proteins paralleled the monocyte chemotactic activity found in the medium of MM-LDL stimulated EC and the levels of MCP-1 mRNA found in the EC. We conclude that (i) SMCF is in fact MCP-1 and (ii) MCP-1 is induced by MM-LDL.

Aorta↗
PubMed1990

Minimally modified low density lipoprotein stimulates monocyte endothelial interactions.

The effect of minimally modified LDL (MM-LDL) on the ability of large vessel endothelial cells (EC) to interact with monocytes and neutrophils was examined. These LDL preparations, obtained by storage or by mild iron oxidation, were indistinguishable from native LDL to the LDL receptor and were not recognized by the scavenger receptor. Treatment of EC with as little as 0.12 micrograms/ml MM-LDL caused a significant increase in the production of chemotactic factor for monocytes (sevenfold) and increased monocyte binding (three- to fivefold). Monocyte binding was maximal after 4 h of EC exposure to MM-LDL, persisted for 48 h, and was inhibited by cycloheximide. In contrast, neutrophil binding was not increased after 1-24 h of exposure. Activity in the MM-LDL preparations was found primarily in the polar lipid fraction. MM-LDL was toxic for EC from one rabbit but not toxic for the cells from another rabbit or any human umbilical vein EC. The resistant cells became sensitive when incubated with lipoprotein in the presence of cycloheximide, whereas the sensitive strain became resistant when preincubated with sublethal concentrations of MM-LDL. We conclude that exposure of EC to sublethal levels of MM-LDL enhances monocyte endothelial interactions and induces resistance to the toxic effects of MM-LDL.

Animals↗
PubMed1978

UCLA Conference. Monocytes and macrophages: functions and diseases.

The mononuclear phagocyte complex is a widespread system of cells originating in the bone marrow monoblast and promonocyte, passing through the intermediate monocyte stage in the blood, and culminating in the tissue macrophages of the lung, liver, spleen, and pleural and peritoneal spaces. The cells are prominently phagocytic and have a well-developed lysosomal system. They function in host defense reactions against micro-organisms, in interactions with lymphoid cells in immunity, in disposal of cell debris, and possible in the regulation of granulopoiesis. Monocytes and the alveolar macrophage are the most accessible cells of this system for study. Several diseases of mononuclear phagocytes have been identified and characterized. These include microbicidal defects associated with increased susceptibility to infection, enzyme defects leading to storage diseases, and neoplastic diseases in which both cell proliferation and biologically active cell products contribute to the clinical disorder.

Animals↗
PubMed1977

Bone-marrow transplantation in acute leukaemia.

Survival in 33 patients with resistant leukaemia treated by marrow transplantation was compared with that of 37 matched patients treated by conventional and experimental chemotherapy. All patients in the transplant group were rendered free of detectable leukaemia for periods of from 36 days to more than 2 1/2 years, while only 6 patients in the chemotherapy group achieved a haematological remission. Overall survival in both groups was poor; however, 5 patients (15%) in the transplant group remain alive and in haematological remission 1--2 1/2 years after transplantation, while no patient in the chemotherapy group survived longer than 13 months. Bone-marrow transplantation appears to offer a small but distinct possibility of long-term survival in patients with acute leukaemia resistant to conventional therapy.

Adolescent↗
PubMed1977

Neutrophil function in bone marrow transplant recipients.

The neutrophil function of seven patients receiving allogeneic bone marrow transplantion was studied. Five of the patients had been transplanted for aplastic anaemia and two for acute leukaemia. Determinations were made of neutrophil phagocytosis, chemotaxis, random migration, and microbicidal activity for Candida albicans and Staphylococcus aureus. One patient showed a decreased ability to kill C. albicans at a time when she had active pneumonia due to Pneumocystis carinii. The remainder of the studies showed normal neutrophil functions. No differences were observed in the patients who had graft versus host disease [GvH] from those without GvH. These studies suggest that defects in phagocytic neutrophil function do not contribute significantly to the impaired host defenses in recipients of bone marrow transplantation.

Acute Disease↗
PubMed1977

Sensitization against non-HLA antigens following bone marrow graft rejection.

A patient with severe aplastic anemia rejected consecutive bone marrow transplants from two HLA-identical sibling donors. Following rejection, the patient developed antibodies that reacted strongly against donor lymphocytes in the complement-dependent cytotoxicity assay. Whereas the reactivity was initially directed specifically against the first marrow donor, cells of both donors and most unrelated individuals were killed by sera obtained after the second injection. These sera were also cytotoxic to the patient's own pre-transplant cells but not to her autologous post-transplant lymphocytes.

Adult↗
PubMed1977

Monocyte function in man.

The monocyte-macrophage cell line is an important member of the host defense system. This report describes a series of assays that can be applied routinely in the evaluation of human monocyte function and gives information as to the activity of normal monocytes in these systems. Tests were chosen to assess various aspects of monocyte function that give some insight into the host defense status and the degree of "activation" of the monocyte. The assays outlined in this report are relatively simple to perform and include measurements of human monocyte chemotaxis, phagocytosis, fungal and bacterial killing, adhesion, and spreading.

Candida albicans↗
PubMed1976

Leukocyte function in familial Mediterranean fever.

Neutrophilic leukocytes of patients with familial Mediterranean fever and of normal control subjects were studied in vitro. FMF neutrophils were found to be morphologically normal by light and electron microscopy and to have normal quantities of the lysosomal enzyme lysozyme. FMF cells demonstrated a slight decrease in their ability to migrate randomly in capillary tubes, this was primarily seen in Armenian patients and in those experiencing an acute attack. The leukocytes of these patients functioned normally in regard to their chemotactic and Candida-killing activity.

Adolescent↗
PubMed1976

Granulocyte function in experimental human endotoxemia.

The effects of endotoxin administration on in vitro granulocyte function were studied in normal man. Four healthy volunteers received an intravenous injection of Pseudomonas endotoxin, 0.1 mug/kg. Endotoxemia resulted in transient neutropenia followed by a rebound neutrophilia. The nadir of the granulocyte count occurred at about 1 hr and maximal neutrophilia 2-4 hr after endotoxin administration. Throughout this time period, neutrophil phagocytosis and killing of Candida albicans were normal, as were resting and postphagocytic glucose metabolism and leukocyte random migration. However, postendotoxin neutrophils demonstrated a markedly decreased chemotactic response in Boyden chambers. The defect was maximal 1 hr after endotoxin administration and persisted 3-4 hr. These observations suggest that, in addition to neutropenia, endotoxin can transiently cause a chemotactic defect or select for a population of circulating neutrophils with an impairment of chemotactic activity.

Blood Bactericidal Activity↗
PubMed1975

Mononuclear phagocyte proliferation, maturation and function.

The mononuclear phagocytic system is a continuum of cells beginning with the bone marrow monoblast and promonocyte, through the monocyte to the larger tissue macrophages and multinucleate giant cells. This system of cells is widely distributed throughout the body in the blood and bone marrow; the pleural, peritoneal, and alveolar spaces; the lymph nodes, spleen, liver, and other parenchymal organs. The activity and composition of the cell varies with the level of maturation, changes in cellular environment, and with various cellular activities. The monocyte-macrophage group of cells plays an active role in defense reactions against certain microorganisms, and in the removal of dying cells and cell debris. They are an integral part of both the inductive phase of the immune response, and of cell-mediated immune reactions. In addition, they probably play a role in the defence against spontaneously arising tumours, in the control of granulopoiesis, and possibly in erythropoiesis.

Animals↗