Deficient display of CD3 on lymphocytes of patients with chronic fatigue syndrome.
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Biomedical subjects
Publications and source records attributed to M L Subirá.
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It is theorized that intermediate filaments are important in the modulation of membrane activity and cell motility; however, their functions are unknown. The assembly and organization of these filaments are under hormonal regulation. We investigated in human monocytes the in vitro effects of Met-enkephalin, Leu-enkephalin, and beta-endorphin on the expression of immunoreactive cytoskeletal vimentin filaments. We simultaneously examined their effect on the phagocytosis of Candida albicans and on the membrane display of surface molecules. The three opioid peptides markedly reduced the expression of vimentin filaments, the phagocytic activity, and the display of HLA-DR molecules at concentrations of 10(-6), 10(-8), and 10(-10) M. On the other hand, the intravenous administration of fentanyl, a synthetic opiate agonist, to patients undergoing surgery induced similar changes in monocytes. In other experiments, 10(-8) M beta-endorphin also decreased the expression of CR3 but did not influence the display of CD13, a surface protein of unknown function. Expression of vimentin filaments correlated directly with the display of HLA-DR antigens and CR3 and with the phagocytic activity. The results of this paper indicate that opiates and opioids, neuropeptides known to be released during stress, can directly depress several monocyte functions. Furthermore, from these data it may be speculated that intermediate filaments may regulate the membrane expression of some surface molecules and the phagocytic process.
We studied monocyte function in 35 consecutive patients with chronic fatigue syndrome (CFS) and 25 healthy controls. Eighty-five per cent of the patients showed monocyte dysfunction characterized by marked reduction in the number of monocytes displaying immunoreactive cytoskeletal vimentin filaments, a low phagocytosis index, and a reduced expression of HLA-DR antigens. These values increased dramatically after incubation of the patients' monocytes with the opioid antagonist naloxone. Other immunological abnormalities also noted in the patients were low lymphocyte blastogenesis and diminished numbers of monocytes displaying receptors for Fc of IgG (FcR) and C3b (CR1). These findings suggest that an increased opioid activity acting through a classical receptor mechanism is active on monocytes from a high proportion of patients with CFS and that this represents a novel example of immunomodulation by opioid peptides in human disease. We suggest that endogenous opioids are involved in the pathogenesis of the chronic fatigue syndrome.
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The effects on natural killer (NK) activity of in vitro incubation of effector cells with staphylococcal Protein A (SPA) and gamma interferon (gamma IFN) in patients with different types of tumors have been compared. The modifications induced in NK activity by these two immunomodulators were assessed using the K-562 cell line and autologous tumoral cells as targets of natural cytotoxicity. The results obtained show that both SPA and gamma-IFN are good inducers of NK activity against the K-562 cell line. SPA always shows itself more efficient than gamma-IFN in increasing the basal level of NK activity. The cytotoxicity against autologous tumoral cells was also greatly increased by the two immunomodulators assayed, SPA being also in this type of assay more efficient than gamma-IFN. Taken the data as a whole the increases induced by SPA and gamma-IFN are parallel both against K-562 and autologous tumoral cells. However when the different types of tumours are considered separately some discrepancies between NK activity against K-562 and autologous tumoral cells appear. The effects of SPA as a modifier of NK activity against autologous tumoral cells looks clear. In our experiments incubation of effector cells with SPA behaves more effectively than the well established gamma-IFN model in the induction of this type of activity. The intimate mechanisms by which SPA exerts its action are quite interesting and merit further investigation.
The possible implications of the plasma contact system in several human pathological conditions have been reviewed. The mechanism of activation and the biochemistry of the different components of this physiological system are described. The activation of the plasma contact system and its important physiological consequences are considered. The implication of the plasma contact system in the pathogenesis of different human and experimental pathological conditions (shock, disseminated intravascular coagulation, extracorporeal circulation...) is reviewed. A particular consideration is given to the pathogenesis of glomerulonephritis where the plasma contact system has been more directly implicated.
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The authors present a study of 50 patients with adenocarcinomas of the colon and rectum, patients with gastric adenocarcinomas, and 30 healthy individuals as a control group. In all subjects the following parameters were determined: total number of lymphocytes in the peripheral blood, T lymphocytes, T-active lymphocytes, and B lymphocytes. A study of the test for lymphoblastic transformation (TTL) with phytohemagglutinin (PHA) stimulation and the determination of alpha-fetoprotein (AFP) and carcino-embryonic antigen (CEA) were also carried out. In patients with gastric adenocarcinoma the results revealed a lymphopenia, especially at the expense of T and T-active lymphocytes, as well as a depression (in 73 per cent) of the lymphocytic response to the PHA stimulation. Patients with carcinoma of the colon showed significant results in the T-active lymphocyte population. In both neoplastic situations the determination for alpha-fetoprotein was negative, while the CEA presented a clear correlation with the evolutive stage of the tumor, being more demonstrative in the tumors located in the colon and rectum.
PURPOSE: Phase II study with intensive chemotherapy and autologous stem cells support in patients with metastatic breast cancer. METHODS: Forty-nine patients were treated with high-doses of two cytotoxic drugs and support with stem cells obtained from several leukapheresis without movilitation. The cells were reinfused forty-eight hours after finishing the administration of chemotherapy. RESULTS: Twenty-one patients (47%, CI-95%: 32.4-63.3%) achieved a complete remission. The objective responses rate was 73% (CI-95%: 57.2-85%). Overall and progression-free survival up to 4 years were 31% and 20%, respectively. Ten patients remain progression-free among 17 and 46 months. The most frequent extramedullary toxicity was hepatic and renal. Three patients (6%) died during the procedure. CONCLUSIONS: Intensive chemotherapy with hematopoietic support yields, with a moderate toxicity, a high objective response and complete remission rate. A small group of patients achieves a long progression-free survival.
The immunosuppressive effect of two of the most used steroids, 16-Methylen-prednisolone and betamethasone, was studied in rabbits sensitized to bovine serum albumin (BSA). In the steroid treated animals the hemagglutination and precipitation titres obtained in Boyden's test and gel-diffusion respectively, were strongly decreased as compared with the controls. The Arthus reaction was also inhibited. No response was detected in the lymphocyte transformation test (LTT) against the antigen (BSA) in the treated animals, and also the PHA induced transformation was suppressed but not completely abolished. A remarked decrease in the number of circulating mononuclear cells was observed in the treated animals. The number of T rosette-forming cells was also strongly decreased, but the percentage of B cells bearing IgG on their membrane detected by immunofluorescence offered only a slight decrease as compared with the controls. All these changes were observed earlier and more intensely in the Betamethasone treated rabbits.
41 patients with clinically demonstrated pollinosis are studied. The following test were performed on all of them: a) Intradermal skin tests using grass pollen extracts (Pangramin III) and with extracts of Dactylis glomerate, Lollium perenne and Poa pratensis. b) Totol serum IgE determination. c) Antigen specific IgE (RAST) determination against the pollens mentioned in b). d) Passive hemagglutination against the pollen Dactylis glomerate. Basing on the results obtained, we have arrived to the following conclusions: 1) IgE determination with intensely positive intradermal skin tests in all cases, gave the following data: 27.5% normal values, 35% slightly elevated and 37.5% highly increased values. We believe that IgE determination can only be used to estimate the "allergization" degree of the patient. 2) No relation between the antigen concentration used in the intradermal skin test, and serum IgE concentration was found. 3) Taking in consideration that the antigen extracts used for RAST and intradermal skin tests were obtained from different sources (Sweden and Spain, respectively), the relation between both determinations ranged between 52.5% and 60%, in a total of 123 tests performed. 4) Considering that in the allergic response antibodies other than reagins (IgG) take part, and taking into account the results obtained with the passive hemagglutination technique, we consider that this last method should be included as a diagnostic routine tool in the pollinic patient.
The role of the autoimmune or autoallergic process in Progressive Chronic Polyarthritis, has been the subject of a great deal of study in the last four decades. In this work, using the synovial fluid of 312 patients suffering Chronic Progressive Polyarthritis and other arthropaties, the immunopathologic aspects of these diseases are studies. The following techniques had been used: 1. Total protein determination 2. Animal immunization. 3. Gel diffusion. 4. Immunoelectrophoresis. 5. Cellogel electrophoresis. 6. Radial immunodiffusion. 7. Absorption. After a systematic discussion of each of the results obtained (comparing these findings with those of other authors) we have arrived to the following conclusions. 1. The great importance of the immunoglobulins' role in the immunization process and their relation with high total protein titres, especially in PCP. 2. The importance of the IgA role in Rheumatoid Arthritis and in Acute Lymphatic Leukemia, behaving in the former as a Rheumatoid Factor with autoantibody nature. 3. An antigenic community between plasma and synovial proteins, and protein fractions. 4. The existence o af synovial "self" protein could not be demonstrated "in vivo".
Three hundred patients whose ages ranged between 10 and 50 years were studied. They were classified, according to the number of sensitizing allergens, their sensitization frequency, the clinical syndrome diagnosed, and the therapy followed by each one of them. Intracutaneous tests with twenty-nine groups of allergens and the determination of total IgE, were carried out on each of them. A statistical evaluation was performed on the results obtained, for the purpose of proving mathematically the certainty of these values. The results obtained lead to the following conclusions: 1) The mean values of IGE found coincide with those discovered by other authors, except in the cases of parasytosis and atopic dermatitis. 2) The expression "mean value of IgE" is incorrect for comparative effects with respect to normal levels, since a great diffusion of individual values with respect to this mean value, were observed in all the circumstances studied. 3) A different reaginic response is noticed in the patients studied: from 50 to 70% presented extremely elevated values of serum IgE. Points 1) and 3) are being submitted to an exhaustive re-examination.
We evaluated in human monocytes the effect of high doses of alfentanyl on the expression of vimentin filaments, the phagocytic activity and the membrane display of HLA-DR molecules in the subjects undergoing surgery. The study was performed on 30 patients, ASAI-II. The patients received 100 mcg/kg i.v. of Alfentanil and the maintenance of anaesthesia was made with Alfentanil (2-3 mcg/kg/min.). The patients were randomized in two groups. The patients were ventilated with N2O:O2 (1:1) (Group I) or air: O2 (1:1) (Group II). After surgery, all patients of the Group II received Naloxone (0.2-0.4 mg). Central venous blood samples were obtained before induction, one and two hours after induction of anaesthesia and at the end of surgery. Separation of monocytes was performed according to Boyum technique. CD35 and HLA-DR molecules and vimentin filaments were studied by indirect immunofluorescence method using monoclonal antibodies. Percentage of positive cells were read with a cytofluorometer. The phagocytic function of monocytes was determined by ingestion of latex particles. Cortisol and ACTH plasma levels were determined by RIA. High doses of Alfentanyl depress phagocytic function and membrane display of CD35 and HLA-DR molecules in monocyte and induce marked changes in the organization of vimentin filaments in these cells in patients undergoing surgery. This monocytic depression was more marked in the patients ventilated with N2O. In our results there was uninhibition of ACTH and cortisol plasma levels responses to surgical stress by Alfentanil administration. Since the effects of Alfentanil were reversed by Naloxone, an opioid receptor mechanism seems to mediate these events.
The in vivo relationship between the immune and the coagulation systems is a well documented fact. In a number of pathological conditions, thrombosis is not understood isolately, but in the context of inflammation and immunity. The mediators in these complex multidirectional interactions are the cytokines, a group of soluble peptides which act on surface cellular receptors, with immunoregulatory properties. These molecules influence negatively the physiological antithrombogenic situation by two different mechanisms. They are involved in processes which disrupt the endothelial integrity, and at the same time, they are capable of activating the endothelium in a prothrombotic manner, by stimulating procoagulant activities and by inhibiting different anticoagulants.
Protein A defined as one of the components of the wall of Staphylococcus Aureus Cowans 1 has shown its effects as modifier of the immune response: it induce changes in cellular receptors, polyclonal activation of T and B lymphocytes, liberation of lymphokines, increase in the production of gamma-interferon (probably as the result of activation of NK cells). In the present work we have studied NK activity and its modifications by Protein A and gamma-interferon in blood of 50 patients with solid tumours. The method used was the Cr 51 liberation assay. The effectors cells were non-adherent lymphocytes treated with different doses and times of incubation of Protein A and gamma-interferon. As target cells we utilized the cellular line K-562 for NK activity and autologous tumoral cells isolated from surgical specimen for tumour-specific cytotoxicity. The results obtained allow us to state the following conclusions: 1. NK activity against K-562 cells is not always a specific parameter of such activity. 2. Tumour-specific cytotoxicity can vary according to the histological type of tumour. 3. Protein A is a potent inducer of tumour-specific cytotoxicity in a higher degree than gamma-interferon.
The percentage and absolute numbers of T, T active and B cells determined by rosette and immunofluorescence procedures, together with the lymphocyte response to PHA stimulation, were studied in 50 patients with colo-rectal adenocarcinoma before surgery. In addition, a group of these patients were tested for the presence of circulating CEA. Sixty percent of the patients studied presented a decrease in absolute numbers of T cells. The percentage and absolute number of Ea rosettes were significantly reduced (p less than 0.01), showing a selective loss of the active T cell subpopulations. In 62% of the cases there was a notable decrease in the lymphocyte response to PHA stimulation. There were no significant variations in the B lymphocyte populations. CEA values showed a close correlation with the clinical tumour staging according to the Dukes classification. Pre-operative immunological testing may have prognostic value in tumours of the large intestine and its results can subsequently be used to evaluate the results of surgery and to indicate avenues which may improve and complete the treatment.
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