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A Rosato

Publications and source records attributed to A Rosato.

64 records · Page 4Linked to original sources

Responses of mouse lymphocytes to extracellular ATP. II. Extracellular ATP causes cell type-dependent lysis and DNA fragmentation.

Extracellular ATP (ATPo) caused dose-dependent lysis of YAC-1 and P-815 mouse tumor cells. This event, assessed by 51Cr release, was accompanied by sustained depolarization of the plasma membrane potential and Ca2+ influx. Plasma membrane depolarization and Ca2+ influx occurred within a few seconds of ATPo addition to both cell types, whereas 51Cr was released without apparent lag in YAC-1 cells and after 2 h in P-815 cells. Furthermore, a rise in [Ca2+]i was required for ATPo-dependent lysis of YAC-1 but not P-815 cells. In P-815 cells, ATPo caused an early and [Ca2+]i-independent DNA fragmentation that occurred at lower nucleotide concentrations than those required to trigger 51Cr release. Instead in YAC-1 cells very low concentrations of ATPo caused early lysis (ED50 for lysis about 200 microM) accompanied by only barely detectable DNA fragmentation. Previous studies disclosed that lymphokine-activated killer cells are fully resistant to the membrane-perturbing effects of ATPo. We show that lymphokine-activated killer cells also do not undergo DNA fragmentation even in the presence of high ATPo concentrations. This study complements previous observations on the lytic effects of ATPo and shows that this nucleotide can also cause DNA fragmentation, one of the earliest target cell alterations observed during CTL-mediated lysis.

Adenosine Triphosphate↗

Interaction of lymphokine-activated killer cells with susceptible targets does not induce second messenger generation and cytolytic granule exocytosis.

CTL activation by specific targets leads to a rapid rise of inositol phosphates (InsPs) and of cytoplasmic-free Ca2+ concentration ([Ca2+]i). While these events are considered necessary to trigger granule secretion, Ca2+-independent cytolytic mechanisms have been recently proposed in addition or as an alternative to the classical Ca2+-dependent exocytosis model. We observed that lymphokine-activated killer (LAK) cells, obtained after stimulation with supraoptimal concentrations of IL-2 in short- or long-term cultures, kill susceptible targets in the absence of a [Ca2+]i rise and InsP3 formation. Moreover, LAK cell-mediated lysis was not associated with an increase in cytotoxic granule exocytosis, as evaluated by BLT-esterase release into the culture supernatant. Furthermore, using an antigen-specific CTL clone, which acquires LAK-like activity when cultured in medium containing high IL-2 doses, second messenger generation and cytolytic granule content secretion were not detected during lysis of unrelated target cells, while killing of specific targets triggered both these processes. These findings suggest that two lytic pathways may coexist in the same effector cells: a second messenger-dependent pathway involving degranulation, which is activated after TCR interaction with specific targets, and another pathway, independent of any known second messenger generation, responsible for unrelated target cell lysis.

Animals↗

The Multiple Sclerosis Cooperative Etiological Study in Italy: preliminary analysis of CSF findings.

295 newly diagnosed Multiple Sclerosis (MS) patients were investigated for interdependence of CSF abnormalities: leukocyte count, CSF/serum albumin ratio, CSF IgG index and intrathecal synthesis of oligoclonal IgG. Only 7% of patients had no CSF abnormality. The most frequent abnormal finding was the presence of intrathecal synthesis of oligoclonal IgG. Polyacrylamide isoelectric focusing appeared more sensitive than agarose electrophoresis for the detection of abnormal CSF fractions. CSF IgG index had low negative and high positive predictive value when compared with electrophoretic methods. Suspected MS had the lowest frequency of abnormal CSF parameters. Patients with oligoclonal CSF bands (OB+) did not differ in age, sex, disease duration or annual bout rate from patients without oligoclonal bands (OB-). CSF leukocyte count was higher in OB+ than in OB- patients. Low CSF cell count was a hallmark of progressive disease. In OB+ patients CSF cell count correlated with CSF IgG index during the first five years of disease and declined with increasing disease duration. In later disease phases CSF IgG index correlated negatively with CSF/serum albumin ratio. 5 years follow-up of this series of patients is in progress to assess the diagnostic and prognostic values of CSF abnormalities in Multiple Sclerosis.

Adolescent↗

Blood-cerebrospinal fluid barrier permeability to serum IgG subfractions and measurement of intrathecal IgG synthesis.

CSF/serum gradients of IgG subfractions separated by isoelectric focusing (IF) have been measured by high resolving laser densitometry. In patients with normal blood-CSF barrier permeability (N.25) and with barrier damage due to acute idiopathic polyneuropathy (N.15) and to medullary compression (N.17), the CSF/serum gradients of IgG subfractions were negatively correlated with their pI. This electrostatic selectivity appeared to be reverted in barrier damage due to acute meningoencephalitis (N.15). In a series of multiple sclerosis patients (N.31), the CSF/serum gradients of IgG subfractions lacking CSF oligoclonal bands have been used to assess the overall barrier permeability to serum IgG. All intra-BCB synthesized IgG subfractions could be measured by densitometry, whereas with other quantitative formulae, 23-26% of the results were false negatives; the total intrathecal IgG amount ranged from 0.01 to 11 mg/dl. The most frequent and prominent fractions appeared to be cathodic. Electrostatic and steric barrier selectivity must be taken into account when the amount of intrathecal IgG synthesis has to be measured.

Adolescent↗

Pyoderma gangrenosum of the "sinus mammarum" in ulcerative colitis.

The first part of this article deals with the report of a patient suffering from pyoderma gangrenosum of the "sinus mammarum" associated with asymptomatic ulcerative colitis. This is followed by a revision of the present epidemiological, etiological, pathogenetic and clinical knowledges about this systemic manifestation of chronic phlogosis of the colon. The Authors have analysed the treatment for this condition and emphasized the resistance of the cutaneous ulcer encountered to conventional medical therapy of the underlying colonic disease which proved to be efficacious only on the latter; this led to integrate traditional treatment with the use of perilesional injections of small doses of calcic heparin as an alternative to immunosuppressive drugs or surgery. Topical antithrombotic treatment, which can be justified by the histological findings of phenomena of the vasculitis in the edge of pyoderma gangrenosum, demonstrated to be crucial and represents a peculiarity in the case here reported, which is unique in the literature as far as the Authors know, since it has not been experimented by anyone else.

Adult↗

[Hemorrhage and gastric perforation in patients with percutaneous endoscopic gastrostomy (PEG)].

INTRODUCTION: PEG is more and more used for those patients who need a medium and above all long term enteral nutrition, especially at home. This is the closest technical system to the requirements to have an ideal nutritional access; however it is burdened, on average in 32.5% of cases, with complications linked to technical mistakes of positioning or to a wrong management, such as haemorrhage and gastric perforation. CASE REPORT: A patient, subjected to supraglottic laryngectomy, to removal of tongue's base and to bilateral laterocervical lymphadenectomy and PEG carrier for 4 months, has arrived to our observation for a clinical outline of acute abdomen for perforation of hollow internal organ, preceded by progressive anaemia due to high digestive haemorrhage. Performed an exploratory laparotomy, it was discovered on the gastric fore face, between body and antrum, in proximity to the small curvature and in front of the PEG gastric access, a perforation with max 2 cm of diameter, crossed by probe's internal disk of retention. They proceeded to remove that, to unstick the gastric stoma from the parietal peritoneum, to suture the access of gastrostomy and the perforation by omentoplasty. Finally they carried out a jejunostomy for enteral feeding. DISCUSSION: We think we can pathogenetically identify the cause of the haemorrhage and of the stomach's perforation, occurred in a short time in the case we have examined, in the probe's movement for incorrect fixing of the plate of external anchorage or for excessive slimming of the patient due to not balanced nutritional supply, as well as in the consequent extension of its intraluminal part with continuous rubbing by internal disk on the gastric wall and with onset decubitus ulcer. Physiopathologic moments, connected with the supposed etiological factor, make both occurred complications as an unique pathologic entity, which has to be observed in the PEG carriers, in order to be able to diagnose it and treat it precociously and above all in order to be able to prevent it. Only a correct technique of positioning and of nursing and of management of nutritional supply is able not to thwart the finality of the PEG device which can be considered, in the elective indications and for the favourable requisites that marks it, a valid access to enteral nutrition realization.

Abdomen, Acute↗

[Intrathecal synthesis of IgG in HIV infections].

CSF and serum of 80 HIV-seropositive patients in various stages of the disease were examined. Total as well as intrathecal IgG synthesis appeared to be frequently elevated in each diagnostic group. Abnormal CSF oligoclonal IgG fractions were significantly more frequent in asymptomatic patients. CSF pleocytosis was found with a lower percentage in neurological AIDS patients. In patients subdivided according to blood T helper cell count, the distribution of the abnormal CSF parameters confirms that the immunological response in the CNS is mediated by interaction with systemic immunity.

Adult↗

[Usefulness of a standardized method for collecting anamnestic data in multiple sclerosis (MS)].

In order to improve the collection of historical data and the evaluation of the clinical course of the disease in MS patients, a standard questionnaire was structured using precise criteria for definition of the disease phase, type of course and symptoms, respectively. A preliminary validation resulted in significant inter- and intra-observer agreement on all collected historical data and definition of lesion localization. Such structured interviews, included in day-to-day clinical care as well as in computerized databases for MS, could improve the possibility of collecting data shareable between different studies and centers.

Data Collection↗

Cerebrospinal fluid (CSF) parameters and clinical course of multiple sclerosis.

The separate correlations among CSF and clinical parameters (mononuclear cell count, assay of intrathecal IgG synthesis, assessment of blood-brain barrier permselectivity to albumin and alpha 2-macroglobulin, detection of oligoclonal intrathecal IgG isoelectric spectro-type; age, disease duration, disability, number of bouts) were investigated by multiple linear regression in 100 multiple sclerosis patients subdivided according to the course and the phase of the disease. Results indicate that the complexity of the oligoclonal CSF IgG isoelectric spectrotype increases, but the overall amount of intrathecal IgG synthesis decreases with increasing number of bouts or disease duration in relapsing remitting and in progressive courses respectively. The CSF mononuclear pleocytosis was low in progressive forms, and it appeared to be linked to the intrathecal IgG synthesis changes. The IgG synthesis rate was proportional to CSF pleocytosis, but a negative correlation between pleocytosis and complexity of CSF IgG spectrotype was found. About 40% of patients had a blood-brain barrier damage. The increased permeability to albumin was related to the number of previous bouts, whereas the CSF pleocytosis seemed to be accompanied by a loss of barrier selectivity to large serum molecules. High CSF IgG index, high mononuclear cell count and low number of prominent oligoclonal CSF IgG fractions characterize the less active or short-lasting disease. Low CSF IgG index with numerous, faint, abnormal IgG CSF bands, low mononuclear cell number and increased barrier permeability to albumin are associated with long-lasting or steady progressive disease.

Adult↗