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Biomedical subjects

M Benedetti

Publications and source records attributed to M Benedetti.

At least 19 recordsLinked to original sources
PubMed1995

Microfilament reorganization during apoptosis: the role of Gas2, a possible substrate for ICE-like proteases.

Gas2, a component of the microfilament system, belongs to the class of gas genes whose expression is induced at growth arrest. After serum or growth factor addition to quiescent NIH 3T3 cells, Gas2 is hyperphosphorylated and relocalized at the membrane ruffles. By overexpressing gas2wt and a series of deletion mutants of the C-terminal region, we have analysed its role in the organization of the actin cytoskeleton in different cell lines. Overexpression of Gas2 deleted at its C-terminal region (delta 276-314 and delta 236-314), but not its wild-type form, induces dramatic changes in the actin cytoskeleton and cell morphology. These effects are not due to interference of the deleted forms with the endogenous Gas2wt function but could be ascribed to a gain of function. We demonstrate that during apoptosis the C-terminal domain of Gas2 is removed by proteolytic cleavage, resulting in a protein that is similar in size to the described delta 276-314. Moreover, by using in vitro mutagenesis, we also demonstrate that the proteolytic processing of Gas2 during apoptosis is dependent on an aspartic acid residue at position 279. The evidence accumulated here could thus represent a first example of a mechanism linking apoptosis with the co-ordinated microfilament-dependent cell shape changes, as possibly mediated by an interleukin-1 beta-converting enzyme (ICE)-like dependent proteolytic cleavage of the Gas2 protein.

3T3 Cells↗
PubMed1994

Nerve growth factor production by lymphocytes.

Nerve growth factor (NGF) is a neurotrophic protein essential for the maintenance and growth of peripheral sympathetic neurons and basal forebrain cholinergic neurons. Recently, NGF has also been shown to have effects on cells of the immune system. In a search for extra neural sources of NGF, we detected NGF-specific mRNA in mouse T lymphocytes of both the CD4+ and CD8+ phenotypes with the use of an RNase protection assay, PCR, and DNA sequence analysis. In CD4+ cells, NGF was present in both Th1 and Th2 Ag-specific clones, but an increase of NGF-specific message was detected after antigenic stimulation only in Th2 clones. NGF mRNA was also detected in splenic B lymphocytes and in a cell line derived from a murine follicular center cell lymphoma. Translation into protein and secretion of NGF were demonstrated by Western blot analysis. The secreted NGF is in an active form capable of inducing differentiation of PC12 cells into sympathetic-like neurons. Furthermore, conditioned medium from clones or lines positive for NGF mRNA was capable of inducing p140 tyrosine kinase autophosphorylation in 3T3 fibroblasts transfected with cDNA encoding for the tyrosine kinase family NGF receptor. We conclude that lymphocytes synthesize and secrete NGF either as a para-autocrine factor acting on the immune system itself, or as a factor for the maintenance of peripheral neurons.

3T3 Cells↗
PubMed1994

p75LNGFR regulates Trk signal transduction and NGF-induced neuronal differentiation in MAH cells.

We have examined NGF-induced signal transduction events and neuronal differentiation in MAH cells, a neuronal progenitor cell line, in which the expression of the two NGF receptors, p140trk (Trk) and p75LNGFR (p75), has been independently manipulated. Coexpression of a large molar excess of p75 substantially enhances the NGF-induced tyrosine autophosphorylation of Trk, compared with cells expressing Trk alone. MAH cells expressing both Trk and p75 stop dividing and acquire a mature neuronal morphology more rapidly and with greater efficiency than MAH cells expressing Trk alone. These biochemical and biological influences of p75 are not observed using a mutant form of NGF that binds Trk but not p75. These data provide evidence that p75 can modulate signal transduction through Trk in a neuronal progenitor cell context and that such modulation has functional consequences for the neuronal differentiation pathway induced by NGF.

Animals↗
PubMed1994

[Malignant tumors of the small intestine. Clinical and therapeutic considerations on 23 observed cases].

Small bowel tumours observed by the Authors at the IInd Surgical pathology of Pavia University between 1974 and 1992 were reviewed. There were found 23 cases; istopathologic findings, clinical presentation, diagnostic aspects and therapeutic options are discussed. The primary role of surgery in the treatment of these cancers is emphasized, but this can be curative only if diagnosis has been timely.

Adenocarcinoma↗
PubMed1994

[Hasharon hemoglobinopathy in a family].

The authors describe an 18 year old athlete, a carrier of Hasharon haemoglobinopathy, pathology which had been checked in some ascendants too. Such a haemoglobinopathy, which has at first been verified in Ashkenazy Hebrew people and is nowadays rather common in North East Italy, shows clinical and laboratory features which are slightly or not at all mentioned in the literature. The leading reference point in the disease's development is the connection between splenomegaly and repetitive low erythrocytosis with serum iron deficiency and increase of the reticulocyte number. The same laboratory data had been observed in his father and in his paternal grandmother; both of them proved to te heterozygous carriers of Hasharon haemoglobinopathy. In all cases we caught the diagnostic validation by the means of isoelectrophoresis involving haemoglobin lysate in polyacrylamide gel. The authors think that the Hasharon shape they verified may be a variant of the classic phenotype: the splenomegaly and erythrocytosis may signify a brisk and primitive erythropoiesis with increasing reticulocytes, which might compensate for the anomalous synthesis of the alpha chains. Serum iron deficiency may signify an increase of the iron consumption. Moreover, the authors do not exclude the possibility of further associational abnormalities.

Adolescent↗
PubMed1993

Differential expression of nerve growth factor receptors leads to altered binding affinity and neurotrophin responsiveness.

The low-affinity p75 neurotrophin receptor is believed to participate with the Trk receptor tyrosine kinase in the formation of high-affinity binding sites for nerve growth factor (NGF). To investigate the functional significance of the two NGF receptors, a truncated p75 receptor was stably expressed in PC12 rat pheochromocytoma cells, yielding cells with greatly reduced levels of wild-type p75 and normal Trk levels. Although these cells were capable of normal differentiation by NGF, very few high-affinity NGF binding sites were detected. These findings indicate that high-affinity binding may be functionally dissociated from biological responses. Furthermore, an increased responsiveness to neurotrophin 3 was observed, as manifested by increased neurite outgrowth. These results suggest that a correct ratio of p75 and p140trk is required to create high-affinity sites and that p75 expression may assist in the discrimination between related but different neurotrophin factors.

Animals↗
PubMed1993

Short term prognosis of stroke in a clinical series of 94 patients.

We conducted a study on the factors predictive of early mortality (within 30 days of onset of symptoms) in a clinical series of 94 patients at their first stroke. Irrespective of the type of stroke, ischemic or hemorrhagic, early mortality proved to correlate with clinical parameters, such as coma at onset, presence of paralysis, changes in ocular motility, and neuroradiological parameters (lesion size on the CT scan) indicative of stroke severity.

Adult↗
PubMed1993

Preliminary study on the effect of broxaterol on bronchial hyperresponsiveness in asthmatic children: influence of allergen exposure.

Increased bronchial hyperresponsiveness (BHR) has been reported in adult asthmatic patients after regular treatment with beta 2-agonists. In this study we evaluated the effect of a 4-weeks treatment period with broxaterol, a new beta 2-agonist, on BHR in asthmatic children living in two different environmental conditions. Two groups of patients, 24 domiciled at sea level, allergen exposed (group 1), and 24 resident at high altitude (Misurina, 1,756 m) in an allergen-free environment (group 2), have been tested. Children were randomly treated with broxaterol 400 micrograms q.i.d. or sodium chromoglycate 10 mg q.i.d. (as control treatment) by the metered dose inhaler for 4 weeks. Pulmonary function tests and methacholine challenge were performed at the beginning and at the end of the study. Throughout the study period a diary card was completed and peak expiratory flow rate (PEFR) was measured three times daily. Forty-two of the patients admitted concluded the study. No significant change was observed in the methacholine PC20 throughout the study period regardless of the type of treatment and/or environment. The amplitude percentage mean of diurnal changes in PEFR during the study period showed no statistically significant differences between treatments or centres, or in the interaction of treatment with centre, time with treatment, time with centre, time with centre and treatment (p > 0.05). Therefore in this pilot study regular treatment with broxaterol for 4 weeks did not cause an increase in BHR in asthmatic children both in conditions of allergen exposure and in an environment free of offending allergens.

Adolescent↗
PubMed1993

Analysis of the trk NGF receptor tyrosine kinase using recombinant fusion proteins.

Nerve growth factor (NGF) represents a family of structurally related trophic factors, including brain-derived neurotrophin factor (BDNF), neurotrophin-3 (NT-3), NT-4, and NT-5. These neurotrophin factors interact with two classes of receptors, the trk receptor tyrosine kinase family, and the low affinity p75 neurotrophin receptor. To study potential ligand-receptor interactions, recombinant trk fusion proteins have been constructed, and pan-trk polyclonal antisera directed against the cytoplasmic tyrosine kinase domain have been generated. The recombinant proteins were assessed for in vitro kinase activity and for the ability of K-252a to inhibit phosphorylation. Antibodies made against the fusion protein recognize all trk family members, and are effective in immunoprecipitation of affinity-crosslinked receptors. Comparative crosslinking indicates that NGF can recognize all trk receptor members, illustrating the large number of potential ligand-receptor interactions between neurotrophins and their receptors.

Animals↗
PubMed1992

Verapamil and flunarizine inhibit phencyclidine-induced effects: an EEG and behavioural study in rats.

The influence of verapamil and flunarizine on phencyclidine-induced effects has been studied in adult male rats. Both verapamil (25 and 100 micrograms/10 microliters, i.c.v.) and flunarizine (40 and 60 mg/kg, i.p.) significantly reduced behavioural (mean intensity of ataxia, mean duration of head weaving) and the EEG (increase in the mean voltage of background activity of the EEG) effects induced by phencyclidine 5 mg/kg (i.p.). It was reported previously that nimodipine and diltiazem significantly potentiate effects induced by phencyclidine. The contrasting results obtained with verapamil and flunarizine, suggest that these drugs may modulate effects induced by phencyclidine by acting at sites other than NMDA receptor-coupled "L"-type calcium channel.

Animals↗
PubMed1992

Evaluation of the allergenicity of infant formulas in a guinea pig model.

In the present study we evaluated the allergenicity of infant formulas using a guinea pig model. Seven groups of ten guinea pigs each maintained on a diet free of cow milk received either water or pasteurized cow milk (PCM) or a conventional cow milk infant formula (CMF) or whey hydrolysate formula (WHF) to drink. On day 37 all the animals were challenged by intravenous injection with 0.5 mL of supernatant of either PCM or WHF. The reactions to the challenge were expressed as none, mild, severe nonfatal, and fatal. A score ranging from 0 to 3 was assigned to each animal and considered in the statistical analysis; P values are expressed as comparisons to the negative water-fed control group. Animals fed WHF and challenged with WHF (group 1), showed 10% fatal reactions and 50% severe but not fatal reactions (P less than .05). When challenged with PCM (group 2), 40% showed a mild reaction. Cow milk formula-fed animals showed 10% fatal reactions and 70% severe reactions when challenged with WHF (group 3). The same challenge caused 40% severe reactions in animals fed PCM (group 4) (P greater than .05). Animals fed and challenged with PCM (group 5) showed 100% fatal reaction (P less than .01). Animals fed water showed no reaction when challenged with either WHF (group 6) or PCM (group 7). The results suggest that WHF has less anaphylactic sensitizing power than PCM and CMF.

Allergens↗
PubMed1991

Inhibition of different dosages of oxatomide or placebo on skin prick test and nasal allergen provocation.

In this two-stage, double-blind study, we evaluated the effects of different dosages of oxatomide (1 and 2 mg/kg/day) on nasal provocation and skin reaction wheal induced by grass-pollen challenge. Children with a positive history of allergic rhinoconjunctivitis and positive responses to skin prick test and nasal provocation test to grass pollen were studied out of season. The results obtained with 1 mg/kg/day of oxatomide demonstrated no significant difference in wheal areas and nasal secretion induced by allergen challenge between treated and untreated patients. The administration of 2 mg/kg/day demonstrated a significant suppression in wheal reaction and nasal secretion induced by specific challenge.

Adolescent↗
PubMed1991

Anaphylactic sensitizing power of selected infant formulas.

The purpose of the present study was to evaluate the anaphylactic sensitizing power of cow milk, soy milk, casein hydrolysate, and a new cow collagen soy protein hydrolysate (CCSPH) infant formula in a guinea pig model of anaphylactic sensitization. Various groups of animals were fed these formulas for 37 days following which they were challenged intravenously either with the sensitizing constituent or one of the infant formulations. The results of these studies indicate a high degree of sensitizing capability of cow milk formula (80% fatal and 20% nonfatal) with reactions in guinea pigs challenged with BLG and no reactions when challenged with casein hydrolysate. In animals sensitized to soy formula there were only nonfatal reactions in 30% when challenged with soy protein. Casein hydrolysate and CCSPH were shown to be nonsensitizing. The results of these studies support he use of derivative infant formulas for the prevention of cow's milk hypersensitivity in infants.

Allergens↗
PubMed1990

Influence of nimodipine and diltiazem, alone and in combination, on phencyclidine-induced effects in rats: an EEG and behavioural study.

The influence of nimodipine and/or diltiazem on the EEG and behavioural effects induced by phencyclidine (PCP) was assessed in adult male Wistar rats. Nimodipine (2 and 10 mg/kg i.p.) and diltiazem (25-100 mg/kg i.p.) significantly potentiated both EEG (increase in background activity voltage, incidence of clustered slow waves) and behavioural (ataxia mean intensity) effects of PCP (5 mg/kg i.p.). A synergistic effect between low, ineffective doses of both nimodipine (0.5 mg/kg i.p.) and diltiazem (5 and 10 mg/kg i.p.) was also found. These data confirm the recent finding of a positive allosteric modulation existing between benzothiazepine (diltiazem) and dihydropyridine (nimodipine) binding sites. They also suggest that the modulation of calcium channels may play a pivotal role in the expression of PCP-induced effects.

Animals↗
PubMed1990

Antibiotic prophylaxis in ear, nose and throat surgery: a comparison of a single preoperative dose with three peri-operative doses of ceftazidime.

An open prospective randomized trial was conducted in three Italian ear, nose and throat (ENT) surgery departments on 120 patients aged 10 to 84 years, to compare a single pre-operative dose vs. three peri-operative doses of ceftazidime in surgical prophylaxis. Sixty patients in group I received 1 g ceftazidime intramuscularly (im) or intravenously (iv) 1 h before surgery, and 60 in group II received three 1 g doses of ceftazidime, im or iv, 1 h before, and 6 and 12 h after surgery. Post-operative infections were observed in six group I patients (10.1%) and seven group II patients (11.6%). All infections arose in patients who had undergone 'moderate-risk' (6.7%) or 'high-risk' surgery (30.5%). We conclude that a single pre-operative 1 g dose of ceftazidime is as efficacious as multiple peri-operative doses in the prophylaxis of infectious complications following this type of surgery.

Adolescent↗
PubMed1990

The efficacy, safety and tolerance of ceftazidime for the treatment of bacterial infections in the elderly.

An open multicentre trial to study the efficacy and safety of ceftazidime in elderly patients has been conducted in four geriatric units on 135 subjects suffering from urinary-tract or respiratory-tract infections. Sixty-two patients were cured (45.9%), and 60 improved (44.4%). Of the evaluable cases bacteriological eradication was achieved in 91.3%. No adverse events were recorded.

Age Factors↗