Biomedical subjects
M Marini
Publications and source records attributed to M Marini.
Scintigraphic assessment of disease activity in psoriatic arthritis with 99m-Tc-labelled non-specific polyclonal human immunoglobulin G.
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[Determination of serum metanephrines in the diagnosis of pheochromocytoma].
Presently, the diagnosis of pheochromocytoma rests upon the determination of urinary catecholamines, and specially metanephrines which offer 100% sensitivity and 97% specificity. The 24 hours urine collection is problematic for practical reasons and patient compliance. Serum metanephrines determination by HPLC (High Performance Liquid Chromatography) avoids these difficulties making the investigation easier. We report the results of serum metanephrine (MN) and normetanephrine (NMN) in 10 patients presenting with a pheochromocytoma histologically confirmed and without renal insufficiency, compared to 18 control healthy subjects, 33 patients suffering from hypertension and 11 patients with terminal renal failure on haemodialysis. The mean value of total metanephrines (MN + NMN) for the patients presenting with a pheochromocytoma is 326 +/- 206 nmol/l (range 76 to 718). In the control group without hypertension this value is 6.8 +/- 2.9 nmol/l (range 0.5 to 10.7) and for the control group with hypertension 25 +/- 27 nmol/l (range 7 to 138). For the patients with renal failure, the mean value is 471 +/- 201 nmol/l (range 188 to 920). Thus total metanephrines serum level values were found higher in the patients with a pheochromocytoma than in those with or without hypertension, but they were not discriminatory when the cases of renal insufficiency were included. CONCLUSION In case of a normal renal function, serum metanephrines determination for the diagnosis of pheochromocytoma gives, above a threshold value of 50 nmol/l, a sensitivity of 100% and a specificity of 94%.
Inhibition of poly(ADP-ribose) polymerization preserves the glutathione pool and reverses cytotoxicity in hydrogen peroxide-treated lymphocytes.
DNA damage caused by oxygen radicals activates poly(ADP-ribosyl) polymerase (pADPRP), a nuclear enzyme that utilizes NAD+ as substrate. It has been demonstrated that pharmacological inactivation of pADPRP rescues human lymphocytes damaged by oxygen radicals, but not those damaged by equitoxic doses of ionizing radiation. In the present paper we demonstrate that the NAD+ pool decreases after both damaging treatments and is preserved in a similar fashion by pADPRP inhibition. On the contrary, the ATP pool, cell energy charge and reduced thiols are decreased only by the administration of oxygen radicals, and are preserved if poly(ADP)ribosylation is inhibited. In fact, treatment with oxidant agents depletes the cell energy pools owing to the simultaneous demands of the glutathione (GSH)/NADPH cycle and pADPRP-driven NAD+ consumption, while in irradiated cells only the latter mechanism operates. We suggest that, when pADPRP is inhibited, enough energy is available for the preservation of cell thiols, thereby allowing oxidant-treated cells to survive and undergo mitosis. Thus, GSH and energy shortage appear to be the main cause of cell death in oxidant-injured cells.
[Islet of Langerhans transplantation in humans].
Islet of Langerhans transplantation is an alternative to whole pancreas transplantation for type I diabetic patients, in whom exogenous insulin therapy has not prevented the occurrence of systemic complications. Thanks to a new isolation technique of human islets, 45 patients have been transplanted worldwide since 1988, of whom only 7 have become totally insulin-independent. Rejection and quality of the islet preparations are problems which remain to be solved. Autotransplantation of islets has been proposed in patients undergoing a pancreatectomy for benign disease. The present report concerns two of our patients who had a pancreatectomy with islet autotransplantation. Both patients are insulin-independent 3 and 11 months postoperatively, with satisfactory metabolic tests. Islet autotransplantation can be proposed when pancreatectomy for non-malignant disease is performed. This method may prevent the development of insulin-dependent diabetes, known to be particularly labile. Because of the sophisticated technical procedures required, human islet isolation is at present only performed in a small number of medical centers and still is in the field of medical experimentation.
Bronchial epithelial cells of patients with asthma release chemoattractant factors for T lymphocytes.
BACKGROUND: T lymphocytes may orchestrate the inflammatory response in atopic asthma, but the mechanisms that promote T-cell accumulation in asthmatic airways are still unclear. In this study, we tested the hypothesis that bronchial epithelial cells of patients with atopic asthma release chemoattractant factors for T lymphocytes. METHODS: Sixteen patients with atopic asthma and eight healthy control subjects were selected for this study. Bronchial epithelial cells were isolated from biopsy specimens obtained by means of bronchoscopy and cultured for 48 hours in serum- and hormone-free medium, with or without 10(-6) mol/L histamine. RESULTS: Only the supernatants of cells from donors with asthma showed chemotactic activity for T lymphocytes, and this was significantly increased (p < 0.025) by exposure to histamine. Chemotactic activity was in part mediated by interleukin-8 (IL-8), because an antibody against human IL-8 significantly reduced it (p < 0.05) and the cell supernatants contained appreciable amounts of immunoreactive IL-8 (0.89 +/- 0.39 ng/ml). Both the residual chemotactic activity of unstimulated epithelial cells and the increased activity caused by histamine were mediated by a single protease-sensitive substance with an apparent molecular weight of 56,000 d and an estimated isoelectric point of 8.8 to 9.1. The partially purified chemoattractant specifically enhanced the migration of CD4+ T lymphocytes, and its activity was inhibited by the univalent Fab fragment of a monoclonal antibody against CD4. CONCLUSION: These results extend our previous observations, indicating an important effector role of bronchial epithelium in asthma.
Differential effect of L-histidine in human lymphocytes damaged by different oxygen radical producing systems.
The effect of histidine on damage induced by oxygen radicals was studied in peripheral blood lymphocytes treated with free oxygen radical-inducing agents: hydrogen peroxide, xanthine oxidase plus hypoxanthine, bleomycin and gamma-rays. L-Histidine, at a concentration of 1 mM, was found to potentiate both cell killing and inhibition of PHA-stimulated cell division brought about by hydrogen peroxide or xanthine oxidase plus hypoxanthine. In contrast, L-histidine did not affect gamma-ray- or bleomycin-induced cell killing and inhibition of PHA-stimulated cell division. We suggest that L-histidine potentiation of cell damage is mainly mediated by interaction of the amino acid with hydrogen peroxide and/or iron rather than with other reactive oxygen species. In addition, these results also indicate that hydrogen peroxide produced by gamma-radiation- or bleomycin-treated cells plays no role in the toxic effects elicited by these agents.
Effect of stimulation on soluble proteolytic enzymes released by peripheral blood mononuclear cells.
The release of soluble peptidases active in the degradation of leucine enkephalin by human peripheral blood mononuclear cells (PBMC), and the effect of stimulation of mononuclear cells on the release of these enzymes are reported. Results obtained indicate that leu-enkephalin is partially degraded in the presence of soluble supernatants prepared from mononuclear cells. In accord with data previously obtained with immunocompetent cell lines, three classes of enzymes appear to be involved in leu-enkephalin hydrolysis: aminopeptidases, dipeptidylaminopeptidases and dipeptidylcarboxypeptidases. Phytohemagglutinin stimulation of mononuclear cells appears to cause a relevant increase of the total activity of the soluble enzymes, as well as a partial rearrangement of the ratio between the different enzyme activities. A similar effect is also evident upon chromatographic separation of the soluble supernatants: the relative activity of the several distinct enzymes--notably aminopeptidases and dipeptidylaminopeptidases--identified after column separation is significantly modified by PBMC stimulation. The effect of stimulation of mononuclear cells on the release of soluble enzymes can be interpreted as an indication of the role of these enzymes--possibly in the regulative process of informational peptides--similar to that described in the case of membrane enzymes.
Enkephalin-degrading dipeptidylcarboxypeptidases in human and Cavia porcellus plasma.
1. The dipeptidylcarboxypeptidases that degrade leucine enkephalin in human and guinea pig plasma were studied by kinetic and chromatographic techniques. 2. The extremely rapid degradation of enkephalins in Cavia plasma seems to be caused by both increased activity of enzymes and reduced role of inhibitors. 3. The increased role of dipeptidylcarboxypeptidases in Cavia as compared to Homo appears prevalently caused by the presence in the former species of a considerable number of very active enzymes. 4. The sum of these data indicates the existence of noticeable intraspecific differences either in peptide-degrading enzymes present in plasma, or in plasma peptides, or in both.
Neuroanatomical and immunohistochemical studies on the dorsal neurons in the spinal cord of Trigla lucerna L. and Scorpaena porcus L. (Scorpaeniformes).
Peculiar dorsal neurons present in the dorsal spinal cord of Trigla lucerna L. and Scorpaena porcus L. were investigated by neuroanatomical and immunohistochemical methods. These neurons were previously defined as commissural cells, but have now been identified as supramedullary neurons. The following fundamental criteria for identifying the supramedullary neurons of Teleosts are proposed: a) dorsomedial location in the spinal cord; b) large size of the soma and axon; c) immunoreactivity to gastrin/CCK-like peptides.
Intraepithelial dendritic cells and selective activation of Th2-like lymphocytes in patients with atopic asthma.
This study examines the distribution of intraepithelial dendritic cells in eight atopic patients with symptomatic asthma and their ability to induce activation of autologous T lymphocytes in vitro. All subjects were sensitized to Dermatophagoides pteronyssinus. The incubation of asthmatic epithelial cells and dendritic cells with autologous resting CD4-positive T cells and purified extracts of D pteronyssinus induced T cell activation and release of high levels of interleukin-4 (IL-4) and interleukin-5 (IL-5). The antigen-presenting activity of dendritic cells was potentiated by epithelial cell-derived granulocyte-macrophage colony-stimulating factor (GM-CSF), since an antibody against GM-CSF reduced it. Circulating monocytes of the two groups of donors were equally effective in promoting selective activation of IL-4- and IL-5-producing T cells. Thus, an interaction between dendritic cells and allergens may favor local activation of CD4-positive T cells with Th2-like function in atopic asthmatic subjects, thereby promoting the expression of the disease.
Bronchoconstrictive responses to inhaled ultrasonically nebulized distilled water and airway inflammation in asthma.
Twenty-two asthmatic patients with a range of airway hyperresponsiveness to methacholine underwent a bronchial challenge with ultrasonically nebulized distilled water (UNDW). The presence of positive responses to this stimulus was related to the extent of airway inflammation, as assessed by histochemical and immunohistochemical evaluation of bronchial biopsy specimens. Twelve patients had airflow obstruction during distilled water inhalation and they showed more severe disease than subjects with no response, as demonstrated by the higher degree of nonspecific bronchial hyperresponsiveness (p < 0.01), higher variability of peak expiratory flow rates (p < 0.01), symptom scores (p < 0.01), and daily use of bronchodilators (p < 0.01). Those patients also had increased numbers of mast cells and eosinophils (p < 0.01) and increased percentage of bronchial epithelial cells expressing endothelin 1 immunoreactivity (p < 0.01). Thus, positive responses to inhaled UNDW reflect the bronchial hyperresponsiveness consistent with moderate to severe asthma and may be due to the release of mediators with bronchoconstrictive properties from inflammatory cells or activated resident cells or both.
[Transplantation of islets of Langerhans in man].
Islet of Langerhans transplantation is an alternative to whole pancreas transplantation for type I diabetic patients, in whom exogenous insulin therapy has not prevented the occurrence of systemic complications. Thanks to a new isolation technique of human islets, 45 patients have been transplanted worldwide since 1988, of whom only 7 have become totally insulin-independent. Rejection and quality of the islet preparations are problems which remain to be solved. Autotransplantation of islets has been proposed in patients undergoing a pancreatectomy for benign disease. The present report concerns two of our patients who had a pancreatectomy with islet autotransplantation. Both patients are insulin-independent 3 and 11 months postoperatively, with satisfactory metabolic tests. Islet autotransplantation can be proposed when pancreatectomy for non-malignant disease is performed. This method may prevent the development of insulin-dependent diabetes, known to be particularly labile. Because of the sophisticated technical procedures required, human islet isolation is at present only performed in a small number of medical centers and still is in the field of medical experimentation.
[Role of integrated imaging (computerized tomography and echography) in the surgical reconstruction of the external ear].
Three-dimensional Computed Tomography (3DCT) imaging methods of the skull and ribs by axial and contiguous slices allow the selective rendering of the involved structures. The possibilities given by variable threshold ranges allow 12-bit density structures (Hounsfield Units) to be obtained within threshold limits. Imaging has been optimized by shading solids. Such methods, together with US (duplex-Doppler) techniques, offer new diagnostic possibilities relative to the treatment planning of patients with either congenital malformations or acquired abnormalities of the external ear and in the evaluation of associated abnormalities of craniofacial areas. In the reconstruction of the earlap by autograft of modelled rib cartilage, after preparing an expanded otomastoid skin flap, the above methods allowed accurate preoperative planning with consequently significant reduction of surgical time and better clinical results. Six patients with earlap abnormalities (four with microtia due to complete hemifacial microsomia syndrome, one with anotia and one with post-traumatic loss of the earlap) were studied for reconstruction. High-quality 3DCT images of the rib and auricolar cartilage were obtained in real-scale representation (1:1 ratio) the evaluation of the donor site and of the autograft size. Useful pieces of information on the development and vascularization of an expanded otomastoid flap, after gradual and constant expansion, were given by duplex-Doppler US, which allowed easy monitoring in both surgical planning and follow-up.
Scintigraphic evaluation of disease activity in rheumatoid arthritis: a comparison of technetium-99m human non-specific immunoglobulins, leucocytes and albumin nanocolloids.
Technetium-99m-labelled, non-specific, polyclonal, human immunoglobulin G (99mTc-hIG) has been used to quantify synovial inflammation in rheumatoid arthritis. A comparison was carried out between the scintigraphic results obtained with this tracer, 99mTc-hexamethylpropylene amine oxime-labelled white blood cells (99mTc-WBC) and 99mTc-albumin nanocolloids (99mTc-NC). Twenty patients affected by rheumatoid arthritis and suffering from clinically active synovitis were studied with 99mTc-hIG. The number and sites of the involved joints had been previously assessed on the basis of the presence of pain and/or swelling. A radiological examination had already been carried out on all the joints. Two days after the 99mTc-hIG scan, 10 patients (group 1) underwent 99mTc-WBC scintigraphy and the other 10 (group 2) underwent a 99mTc-NC scan. The results show that the results of 99mTc-hIG and 99mTc-NC scans are in agreement with clinical examinations in the majority of cases. However, a certain number of positive joint scans corresponding to negative clinical examinations was found. The numerical distribution of these results according to the radiological stages seems to show that 99mTc-hIG is more useful than 99mTc-NC in the initial phases of the disease. The 99mTc-WBC scan was negative in a consistent percentage of the joints previously assessed as clinically and 99mTc-hIG scan positive.
Soluble enkephalin-degrading enzymes released by lymphomic and erythroleukaemic cell lines.
The possible existence of soluble proteolytic enzymes released by cells of lymphomic (U937 and 1301) and erythroleukaemic (K562) lines was studied measuring the hydrolysis of 3H-leucine enkephalin in the presence of cell-free supernatants obtained from these lines. Results indicate that leu-enkephalin is rapidly degraded in the presence of these supernatants, and that enkephalin disappearance is paralleled by the formation of peptides that can be interpreted as its hydrolysis fragments. To characterize the factors involved in leu-enkephalin degradation, cell supernatants were analyzed by ion exchange and by steric exclusion chromatography. Data obtained indicate the presence of three groups of proteins active in leu-enkephalin degradation: aminopeptidases, dypeptidylaminopeptidases and dypeptidylcarboxypeptidases. In all three lines, these enzymes are represented by a considerable number of distinct activities. The sizable number of soluble enzymes identified and the significant total activity observed suggest a possible role in the regulatory degradation of informational peptides, as proposed by several groups for the membrane-bound proteolytic enzymes of immunocompetent cells.
Evaluation of the performance of the copper T380A IUD up to ten years. Is this IUD a reversible but potentially permanent method?
The clinical experience of a cohort of 340 women using a TCu380A IUD for up to 10 years at the Family Planning Clinic of the State University of Campinas, Brazil was evaluated by life-table analysis. Removals for medical reasons were more frequent during the first year of use, while from the third year on, removals for personal reasons were more frequent. Expulsions were concentrated in the first two years of use, and none were detected after the fourth. Gross pregnancy rate accumulated to 2.0, 2.8 and 5.3 and continuation rate was 64.2, 43.4 and 27.8 per 100 women at three, six and ten years of use, respectively. The effectiveness of the device did not decrease significantly after the eighth year of use and it could be considered a reversible but potentially permanent method.
No relationship between anatomic damage and disability in rheumatoid arthritis (RA). A retrospective assessment.
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