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M Ghirardi

Publications and source records attributed to M Ghirardi.

28 records · Page 2Linked to original sources
PubMed1995

A novel intermediate stage in the transition between short- and long-term facilitation in the sensory to motor neuron synapse of aplysia.

A major difference between short- and long-term memory is that long-term memory is dependent on new protein synthesis. Long-term memory can be further subdivided into a transient, initial phase that is readily susceptible to disruption and a later, more stable and persistent stage. To analyze this transition on the cellular level, we have examined the steps whereby short-term facilitation is converted to a long-term form in the sensorimotor connection of the Aplysia gill-withdrawal reflex. We found that stable long-term facilitation (at 24 hr) requires a higher concentration (100 nM) of serotonin (5-HT) than does short-term facilitation (10 nM). By using low concentrations of 5-HT, which do not produce long-term facilitation, we now have been able to explore the intermediate phases between the short- and long-term processes. By this means we have uncovered a new transient phase that involves three mechanistically different mechanisms--covalent modification, translation, and transcription--each of which can be recruited as a function of the concentration of 5-HT.

Animals↗
PubMed1994

C/EBP is an immediate-early gene required for the consolidation of long-term facilitation in Aplysia.

The consolidation of long-term memory requires protein and mRNA synthesis. A similar requirement has been demonstrated for learning-related synaptic plasticity in the gill-withdrawal reflex of Aplysia. The monosynaptic component of this reflex can be reconstituted in vitro, where it undergoes both short- and long-term increases in synaptic strength in response to serotonin (5-HT), a neurotransmitter released during behavioral sensitization, a simple form of learning. As with sensitization, the long-term synaptic modification is characterized by a brief consolidation period during which gene expression is required. We find that during this phase, the transcription factor Aplysia CCAAT enhancer-binding protein (ApC/EBP) is induced rapidly by 5-HT and by cAMP, even in the presence of protein synthesis inhibitors. Blocking the function of ApC/EBP blocks long-term facilitation selectively without affecting the short-term process. These data indicate that cAMP-inducible immediate-early genes have an essential role in the consolidation of stable long-term synaptic plasticity in Aplysia.

Amino Acid Sequence↗
PubMed1992

Roles of PKA and PKC in facilitation of evoked and spontaneous transmitter release at depressed and nondepressed synapses in Aplysia sensory neurons.

Two second messenger pathways, one that uses the cAMP-dependent protein kinase A (PKA), the other that uses protein kinase C (PKC), have been found to contribute to the short-term presynaptic facilitation of the connections between the sensory neurons in Aplysia and their target cells, the interneurons and motor neurons of the gill-withdrawal reflex. To study their relative contributions as a function of the previous history of the neuron's activity, we have examined the effects of inhibiting PKA (using Rp-cAMPS) and PKC (using H7) on the short-term facilitation of spontaneous release as well as of the evoked release induced by serotonin at nondepressed, partially depressed, and highly depressed synapses. Our results suggest that whereas activation of PKA is sufficient to trigger the facilitation of nondepressed synapses, activation of both PKA and PKC is required to facilitate depressed synapses, with the contribution of PKC becoming progressively more important as synaptic transmission becomes more depressed.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMedDate not supplied

[Non-polyposis colorectal cancer in subjects under 55 years of age: frequency and phenotype of hereditary or familial syndromes].

Young age is believed to be a risk factor for hereditary or familial non-polyposis colorectal cancer. Present study analysed frequency, phenotype and familial cancer risk of 82 subjects with colorectal cancer under 55 years of age. According to age and family history, probands have been subdivided into 5 groups: Hereditary Non-Polyposis Colorectal Cancer (HNPCC) (8.2% of cases); Suspected HNPCC (7.3%); Non-specific familial aggregation of colorectal cancer (AFACC) (19.5%); Early-onset colorectal cancer (diagnosis under 35 years of age) (CCG) (6.1%); Sporadic colorectal cancer (CCS) (58.5%). Proportions of probands with multiple colonic tumours were highest in HNPCC (57.1%), but present in AFACC (12.5%) and CCG (20.0%) groups, as well. Extracolonic, in particular endometrial and ovarian cancers have been found in HNPCC and AFACC probands. Tumours of proximal colon were most frequent in HNPCC, suspected HNPCC, CCG patients. Eleven-years survival rate was higher in HNPCC probands then in CCS group. Familial cancer risk in HNPCC was 3 times as much as in CCG + CCS groups. Diagnosis of colorectal cancer under 55 years of age is associated with an high frequency of hereditary or familial cases. Genetic tests, surveillance and screening programs in these patients must be based on extensive phenotype and pedigree analyses. HNPCC is widely represented in young colorectal cancer patients and is associated with a high risk of multiple synchronous or metacronous colonic and extracolonic tumours. Total colectomy and eventual hysterectomy with bilateral oophorectomy seem therefore recommendable options in these patients.

Adenocarcinoma↗
PubMedDate not supplied

Distribution of 1,2 DMH-induced colonic aberrant crypt foci after administration of a gastrin receptor antagonist (CR2945), in the murine model.

Our previous experimental data demonstrated that a new gastrin receptor antagonist (CR2945) has a chemopreventive effect on dimethylhydrazine-induced colon cancer in mice. The aim of this study is to test the effect of CR2945 on the appearance and distribution of aberrant crypt foci (ACF), proposed as early "preneoplastic" lesions in colon carcinogenesis, in the murine model. 176 CD1 male mice were randomly divided into 4 groups: group 1, sham group received 2 daily intra-peritoneal injections of saline solution; group 2 received 1 weekly intra-peritoneal injection of DMH 20 mg/kg, for 5 weeks, and 2 daily intra-peritoneal injections of equal volume of NaCl 0.9%; group 3 and 4 received the same weekly dose of DMH and 2 daily injections of CR2945 at the respective doses of 2.5 and 7.5 mg/Kg for 5 weeks. The rodents were sacrified 15, 20, 25, and 38 weeks after receiving the first injection. The number of ACF per area (ACF frequency), their multiplicity (number of crypts per focus), ACF frequency according to each colonic site were recorded. No ACF were found in the sham group. No substantial differences were observed in ACF distribution between the remaining groups. Our hypothesis is that CR2945 does not alter the final number of ACF but might induce a regression of some dysplastic ACF.

1,2-Dimethylhydrazine↗
PubMedDate not supplied

[Course and natural history of idiopathic ulcerative proctitis in adults].

BACKGROUND AND AIMS: Epidemiological studies have shown that ulcerative proctitis represents 25-55% of ulcerative colitis. In western countries, the incidence of ulcerative proctitis has been increased, while the incidence of more extensive colitis remained unchanged. Compared with extensive ulcerative colitis, the idiopathic proctitis seems to be a benign disease, with an extension to proximal segments in less than 30% of cases, low surgical and cancer risk. On the basis of epidemiological studies, not confirmed by endoscopic and histological features, it has been hypothesized that ulcerative colitis and proctitis could represent two different clinical entities. The aim of the study was to evaluate some clinical and demographic features related to the two different localizations, colitis and proctitis, in the attempt to clarify the above mentioned issues. METHODS: Demographic data of 156 patients observed in our institution from 1982 to 1999, were retrospectively analysed. Diagnosis, extension and severity of ulcerative procto-colitis were based on endoscopic and histological criteria. Local and systemic symptoms, extraintestinal manifestations, surgical and cancer risk, were also recorded. RESULTS AND CONCLUSIONS: Ulcerative proctitis has shown to be a benign disease, with a prevalence of local symptoms, less systemic and extraintestinal manifestations, and low endoscopic grades of activity. Furthermore no surgical intervention and cancer development were recorded. Extension to proximal segments was observed in 10.25% of cases. Young age of onset of symptoms,-smoking and appendectomy were associated to an higher risk of extension of the disease.

Adolescent↗
PubMedDate not supplied

Surgical treatment of inflammatory bowel diseases in northwestern Italy: a multicentric study by the G.S.M.I.I. (Inflammatory Bowel Disease Study Group).

BACKGROUND AND AIMS: Improved medical therapy and bowel sparing and sphincter saving techniques have changed surgery for UC and CD. Collaboration between gastroenterologists and surgeons is necessary to uniform the indications for surgical treatment reducing emergency operations. GISMII multicentric study aimed to show indications, timing and impact of surgery, through retrospective analysis of cases observed between 1992 to 1996. METHODS: Data were obtained by 16 departments of General Surgery. RESULTS: 102 UC and 376 CD patients were analyzed. In UC patients surgery was performed for failure of medical therapy in 54%, complications in 28.4%, cancer or dysplasia in 10% of cases, 83.3% elective procedures. 30.4% ileo-anal pouch, 30.4% total procto-colectomies with definitive ileostomies, 32.4% total colectomies with ileo-rectal anastomosis, 6.8% segmental resections, were performed. In CD patients surgery was performed in 21% for medical therapy failure, in 79% for complications. 53.4% of patients were submitted to 1 operation, 84% elective procedures. Reoperations were performed in 46.6% of patients, 70.3% elective procedures. In the first operation bowel resection was performed in 79.1%, stricturoplasty in 14.3%; in the subsequent operations bowel resection 62.8%, stricturoplasty 21.7%, increasing number of temporary or definitive ileo-stomies. CONCLUSIONS: Collaboration between gastroenterologists and surgeons is necessary to obtain optimal results, reducing the incidence of emergency surgery, and complications. The short period observed between diagnosis and operation (21.4 months) is due to the increasing tendency of gastroenterologists to anticipate a surgical procedure when young patients with a chronic disease need a prolonged medical therapy.

Adolescent↗
PubMedDate not supplied

[Surgery in severe ulcerative colitis: our experience].

BACKGROUND AND AIMS: The mortality in severe episodes of ulcerative colitis (UC) has been reduced from 31-61% in the 1950 to 1-3%. Nevertheless it remains high in non specialist centers. Simple criteria are necessary to predict the outcome of severe ulcerative colitis. METHODS: 14 patients hospitalized for severe disease (Truelove and Witts criteria) from 1996 to 2000 were retrospectively analyzed. Patients were divided into two groups: 1. Group A: patients with severe disease surgically treated. 2. Group B: patients with severe disease responders to medical therapy Sex, age, length of steroids medical therapy, fever, stool frequency, CRP, ESR, haemoglobinemia, leukocytes, serum albumin values in the three days before the operation or during the hospitalization were collected. RESULTS: Total colectomy with ileostomy was necessary in 8 patients (57.1%), while 6 patients (42.90%) were responders to medical therapy. No perioperative mortality was recorded. Stool frequency, CRP, ESR, haemoglobinemia, serum albumin were significantly related to surgical operation. CONCLUSIONS: 1. No uniform criteria off severe attacks, are clearly defined in Literature. 2. The length of pre-operative medical therapy has a tendency to be too high (in our series 19 + 8.2 days). 3. Stool frequency, CRP, ESR, haemoglobinemia, serum albumin were significantly modified in operated patients.

Adult↗
PubMedDate not supplied

[Evaluation of the results after 5 year from a vertical banded gastroplasty: our experience].

BACKGROUND AND AIMS: vertical banded gastroplasty (GPV) is the most frequently performed restrictive procedure for morbid obesity, but long-term follow-up is almost nonexistent. A poor outcome after GPV and a low quality of life has been reported. The aim of the study was to determine long-term outcome after 5 years follow-up. METHODS: 225 GPV were performed from 1995 to 2002. Patients were followed every month in the first three months, after 6 and 12 months, and subsequently every year. RESULTS: No mortality was observed. One gastric fistula, treated with medical therapy, was the single related complication observed. Vomiting occurred in 21.2% of patients. After 2 years 74.5% of patients had a BMI < 35, with a decrease of IEW = 50% (IEW% L 54.1%, 56.4%, and 57.1% after 12, 24 and 60 months, respectively). After 5 years, the results were unsatisfactory in 17.1% of patients; 8 patients underwent bariatric re-operation with good results. CONCLUSIONS: GPV represents a safe procedure with a low incidence of complications, with poor results in 17.1% of patients. Pre-operative identification of non responders is achievable with "BIB test". In the responders significant dietary changes are complained.

Adult↗