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Biomedical subjects

L Beretta

Publications and source records attributed to L Beretta.

At least 55 records · Page 3Linked to original sources
PubMed1996

Rapamycin blocks the phosphorylation of 4E-BP1 and inhibits cap-dependent initiation of translation.

The immunosuppressant drug rapamycin blocks progression of the cell cycle at the G1 phase in mammalian cells and yeast. Here we show that rapamycin inhibits cap-dependent, but not cap-independent, translation in NIH 3T3 cells. Cap-dependent translation is also specifically reduced in extracts from rapamycin-treated cells, as determined by in vitro translation experiments. This inhibition is causally related to the dephosphorylation and consequent activation of 4E-BP1, a protein recently identified as a repressor of the cap-binding protein, eIF-4E, function. These effects of rapamycin are specific as FK506, a structural analogue of rapamycin, had no effect on either cap-dependent translation or 4E-BP1 phosphorylation. The rapamycin-FK506 binding protein complex is the effector of the inhibition of 4E-BP1 phosphorylation as excess of FK506 over rapamycin reversed the rapamycin-mediated inhibition of 4E-BP1 phosphorylation. Thus, inactivation of eIF-4E is, at least in part, responsible for inhibition of cap-dependent translation in rapamycin-treated cells. Furthermore, these results suggest that 4E-BP1 phosphorylation is mediated by the FRAP/TOR signalling pathway.

3T3 Cells↗
PubMed1996

Cerebral ischemia after venous air embolism in the absence of intracardiac defects.

Cerebral air embolism occurred in a patient undergoing posterior fossa surgery performed in the sitting position for acoustic neuroma removal. The patient experienced two episodes of venous air embolism, as evidenced by precordial Doppler, end-tidal carbon dioxide reduction, and oxygen desaturation. In both cases, air was aspirated from the central venous catheter; during the second episode there was arterial hypotension and electrocardiogram changes, and air bubbles were visualized in the cerebellar arteries. The patient did not regain consciousness after surgery and developed early tonic-clonic convulsions and electroencephalogram status epilepticus, which was treated with barbiturate coma. Intracardiac septal defects were not detected by transesophageal echocardiography, and computerized tomography of the brain demonstrated multifocal discrete ischemic areas in the cerebral hemispheres. The patient died 6 days after surgery without having regained consciousness. This case appears to represent the occurrence of transpulmonary passage of venous air embolism.

Brain Ischemia↗
PubMed1996

Rapamycin stimulates viral protein synthesis and augments the shutoff of host protein synthesis upon picornavirus infection.

The immunosuppressant drug rapamycin blocks progression of the cell cycle at G1 in mammalian cells and yeast. We recently showed that rapamycin inhibits both in vitro and in vivo cap-dependent, but not cap-independent, translation. This inhibition is causally related to reduced phosphorylation and consequent activation of 4E-BP1, a repressor of the function of the cap-binding protein, eIF4E. Two members of the picornavirus family, encephalomyocarditis virus and poliovirus, inhibit phosphorylation of 4E-BP1. Since translation of picornavirus mRNAs is cap independent, inhibition of phosphorylation of 4E-BP1 could contribute to the shutoff of host protein synthesis. Here, we show that rapamycin augments both the shutoff of host protein synthesis and the initial rate of synthesis of viral proteins in cells infected with encephalomyocarditis virus and poliovirus.

3T3 Cells↗
PubMed1996

[Adequacy of admission in neurosurgical intensive care].

OBJECTIVE: The Intensive Care Units of Milano metropolitan area are characterized by difficulties of hospitalization for acutely injured patients due to the low bed availability. We evaluated the problem trying to find out possible solutions. DESIGN: On the day of achieved neurological and neurosurgical stability-defined as the day when the intracranial pressure and jugular venous oxygen saturation monitoring, hyperventilation, osmotic therapy were considered no longer needed--the monitoring procedures and instrumental and/or pharmacological treatments that the patients received were recorded and classified as follows: 1) intensive, 2) intermediate, 3) non-intensive. PATIENTS: All the acutely injured patients admitted at five Neurosurgical ICUs during June-July and October-November 1994 have been studied. Only one of these ICUs had a "sub-intensive unit". MEASUREMENTS AND MAIN RESULTS: 391 patients (29.9%) aneurysms and arteriovenous malformations, 25.1% tumours, 2.8% head injuries, 8.7% spontaneous intracranial haematomas, 13.5% various pathologies) were studied. Out of them 358 had an acute brain failure. 16.5% died during brain failure and 83.5% reached neurological stability within 3 days. When neurological stability was reached 32.1% of patients could be classified as "intensive", 63.6% as "intermediate" and 4.3% as "unintensive". In the four ICUs, without sub-intensive ward facilities, 361 patients were admitted with a total amount of 2292 days of hospitalization. Among them 61.9% were spent for a) patients with no brain injury (32 pts/113 days), b) postoperative patients (113 pts/167 days), c) patients in stable neurological conditions (159 pts/1139 days). Therefore, only 38% of the days recorded were given to patients that needed neurointensive care. CONCLUSION: Out data suggest that the receptivity for acute injured patients could be increased creating recovery room units and intermediate post-intensive units together with a better interchange between general and neurosurgical ICUs.

Adult↗
PubMed1995

Stathmin is a major substrate for mitogen-activated protein kinase during heat shock and chemical stress in HeLa cells.

Stathmin is a ubiquitous, highly conserved 19-kDa cytoplasmic protein whose expression and phosphorylation are regulated in relation to cell proliferation, differentiation or activation, in many biological systems. In this report, we show that stathmin undergoes major phosphorylation in HeLa cells submitted to heat or chemical stress. Heat-shock-induced stathmin phosphorylation was very rapid, as maximal incorporation of phosphate was observed at 5 min. Phosphorylation of stathmin might, therefore, occur as a very early step in the intracellular response to heat shock. The sites of phosphorylation of stathmin involved during the stress response were identified as mostly Ser25 and, to a lesser extent, Ser38. These sites are both followed by a proline residue, and known to be good substrates in vitro for mitogen-activated protein kinase (MAP-kinase) and p34cdc2 kinase, respectively. In lysates from heat-shocked cells, an increased stathmin-kinase activity, distinct from the histone-H1-kinase activity, was found to phosphorylate stathmin mostly on Ser25, the main site for MAP-kinase in vitro. This stathmin-kinase coeluted quantitatively with the stress-activated MAP-kinase from an FPLC MonoQ column. Furthermore, a stathmin kinase activity was precipitated from lysates of heat-shocked HeLa cells by an anti-(MAP-kinase) serum. Together, these results indicate that the phosphorylation of stathmin by MAP-kinase is likely to be a significant component of the signalling array controlling the cellular response to stress, and they further underline the general involvement of stathmin in intracellular signalling.

Enzyme Activation↗
PubMed1995

Magnetic resonance imaging of cerebral fat embolism: a case report.

Fat embolism syndrome (FES) is one of the most important causes of morbidity and mortality following multiple fractures. Neurological involvement (cerebral fat embolism) has been reported frequently. A case of cerebral fat embolism is reported. While CT scan revealed no abnormalities, MRI, performed in this patient 8 days after trauma, showed relative low-intensity areas on T1-weighted images and high intensity areas on T2-weighted images involving cerebral white matter, corpus callosum and basal ganglia. MRI follow-up (1 and 3 months post-trauma) showed nearly complete resolution of the abnormal signal. MRI seems to be a useful diagnostic tool for detecting and quantifying lesions in fat embolism syndrome.

Accidents, Traffic↗
PubMed1995

Left ventricular diastolic parameters in 288 normal subjects from 20 to 80 years old.

Left ventricular diastolic indexes are influenced by several variables. In order to evaluate the relationship of these indexes to age, heart rate, sex and to standard echo parameters, 288 normal subjects aged from 20 to 80 years, divided into six age groups, underwent a two-dimensional colour Doppler examination. Doppler examination was performed from the apical four chamber view to evaluate transmitral flow; isovolumic relaxation time (IVRT) was measured from an apical five chamber view. In order to obtain a sufficient number of subjects for an adequate statistical analysis, seven hospitals were involved in the study. Univariate analysis showed that age influences the peak velocity of the E (r = -0.46) and A waves (r = 0.46), the E/A ratio (peak velocities) (r = -0.69), the A wave integral (r = 0.48) and the E/A integral ratio (r = -0.57), the early and late filling fractions (r = -0.48 and r = 0.51 respectively), and the E wave deceleration (r = -0.43) and deceleration time (r = 0.36). In subjects older than 70 years an inversion of the E/A wave ratio was observed. Multivariate analysis confirmed that age has an important influence on left ventricular diastolic indexes but also demonstrated that heart rate has a significant influence. Sex, ejection fraction (EF), and the dimensions of the mitral annulus and the left ventricular posterior wall had less influence on left ventricular diastolic indexes. The mean values of E and A wave acceleration, deceleration and peak velocity were used to depict left ventricular filling morphology in various age groups for three different heart rate values. The conclusions of the study, are: (1) normal left ventricular diastolic parameters were obtained as mean values at seven different hospitals (2) when evaluating left ventricular diastolic function parameters it is important to take into account age and heart rate; E/A inversion in older subjects should be considered the normal mitral flow pattern.

Adult↗
PubMed1995

Sclerotherapy plus octreotide versus sclerotherapy alone in the prevention of early rebleeding from esophageal varices: a randomized, double-blind, placebo-controlled, multicenter trial. New Italian Endoscopic Club.

Because of its ability to decrease portal pressure, azygos blood flow, and postprandial splanchnic hyperemia, octreotide administration could be effective in reducing early rebleeding in patients undergoing endoscopic variceal sclerotherapy (EVS). We report the results of a trial comparing EVS + octreotide versus EVS alone. Consecutive patients with cirrhosis and endoscopically proven variceal hemorrhage were considered eligible for the trial if hemodynamically stable for at least 24 hours after bleeding stopped. Patients with advanced liver cancer or having received EVS treatment in the past were not enrolled. After enrollment patients were submitted to EVS (day 1); all patients were randomized to receive octreotide, 100 micrograms three times a day subcutaneously, or an identical placebo, up to day 29; EVS was repeated at days 8, 15, and 29. Fifty-eight patients were randomized to receive either EVS + octreotide (n = 26) or EVS alone (n = 32). The two groups were evenly balanced for sex, age, Child-Pugh class, history of previous bleeding, endoscopic appearance of varices, or treatment received in emergency. Eight of 26 (31%) patients in the EVS + octreotide group rebled, compared with 11 of 32 (34%) in the EVS group. Four of the eight (50%) patients in the former group and 8 of 11 (73%) in the latter, respectively, bled within day 15. There were 10 (38.5%) deaths in the EVS + octreotide group (seven bleeding-related), compared with seven (21.9%) (five bleeding-related) in the EVS group; these differences did not reach statistical significance. Administration of octreotide, 100 micrograms three times a day, subcutaneously, to patients undergoing EVS for prevention of recurrent variceal bleeding does not decrease the incidence of early rebleeding.

Aged↗
PubMed1995

[Dilated cardiomyopathy: a new natural history? The experience of the Italian Multicenter Cardiomyopathy Study (SPIC)].

BACKGROUND: The natural history of idiopathic dilated cardiomyopathy (IDC), once a disease with a dire prognosis, is thought to be changing. Aim of this study was to describe the clinical characteristics, long term course and prognostic factors of IDC patients followed up prospectively since the late eighties. METHODS: Patients with a diagnosis of IDC confirmed by normal coronary angiography, non specific endomyocardial biopsy findings and a left ventricular ejection fraction below 50% were consecutively enrolled in a multicenter registry and followed up at 6-months intervals. RESULTS: From January 1986 till January 1994, 441 IDC patients with a mean age of 43 +/- 13 years (range 8-68) entered the registry. Thirty per cent of patients were women and 8% had familial dilated cardiomyopathy. NYHA class was I-II in 77% and 35% of patients were asymptomatic at the time of diagnosis. Treatment included digitalis in 235 patients (53%), diuretics in 239 (54%), angiotensin converting enzyme inhibitors in 269 (61%), betablockers in 108 (24%). Chronic atrial fibrillation was detected in 10% of patients and left bundle branch block in 24%. Mean cardiothoracic ratio was 0.54 +/- 0.06. Mean left ventricular end diastolic dimension was 38 +/- 6 mm/m2; 48% of patients had minimal or mild left ventricular dilatation. Mean left ventricular ejection fraction was 30 +/- 10%. At Holter monitoring 67% of cases had complex ventricular arrhythmias, 37% had ventricular tachycardia and 4% had advanced atrioventricular block. Mean exercise stress test duration was 9 +/- 4 minutes. After a mean follow up of 31 +/- 24 months, 337 patients were alive without transplantation and 5 were lost to follow up; 60 patients (14%) had died of cardiac causes, namely heart failure (6%), sudden death (7%) and pulmonary embolism (< 1%) and 30 had been transplanted (7%), while 4 had died of unclear causes. Survival and transplant-free survival were 94% and 90% at 2 years and 82 and 76% at 5 years, respectively. At multivariate analysis pulmonary capillary wedge pressure (p = 0.0001, odds ratio, for values > 15 mm Hg, 2.05) and betablocker treatment (p = 0.002, odds ratio 0.26) were independent predictors of survival. CONCLUSIONS: In this large, multicenter prospective study, prognosis of IDC in the eighties appears to be improved. Early diagnosis, together with improved medical treatment, probably bears a causal relation to these changes.

Adolescent↗
PubMed1995

[Surgery of abdominal aortic aneurysm and concomitant disease of the digestive tract].

The incidence of intra-abdominal diseases associated with abdominal aortic aneurysm is increasing, and it is difficult to decide whether to operate the abdominal disease first, the aneurysm first or both simultaneously. Variables used in decision analysis include type, stage and life expectancy of the cancer, rupture rate of abdominal aortic aneurysm. Symptomatic lesion should be treated first. Absolute indication for operation initially on the aneurysm is the presence of symptoms of rupture. Aortic abdominal aneurysmectomy combined with surgical removal of an intestinal disease may present severe risks as infection of the graft and anastomotic leakage, especially during lower abdominal surgery. In this paper authors present four cases of AAA which had intra-abdominal surgical disease. They were treated by one-stage operation with no complications. Criteria to assess timing of surgical treatment of abdominal surgical diseases concomitant to AAA are discussed.

Aged↗
PubMed1993

Multiple phosphorylation of stathmin. Identification of four sites phosphorylated in intact cells and in vitro by cyclic AMP-dependent protein kinase and p34cdc2.

Stathmin is a ubiquitous, highly conserved phosphoprotein which most likely acts as a relay integrating various intracellular pathways regulating cell proliferation, differentiation, and functions. At least 14 molecular forms of stathmin have been identified so far, which migrate as 2 unphosphorylated and 12 increasingly phosphorylated spots (M(r) = 19,000-23,000; pI = 6.2-5.6) on two-dimensional electrophoretic gels, and whose pattern may reflect the state of activation of cells. We found that stathmin could be phosphorylated in vitro by at least three different protein kinases: cAMP-dependent protein kinase, p34cdc2, and casein kinase II, cAMP-dependent protein kinase catalyzed the phosphorylation of stathmin on serines 16 (K-R-A-S) and 63 (R-R-K-S), whereas p34cdc2 induced phosphorylation on serines 25 (I-L-S-P-R) and 38 (P-L-S-P-P-K-K-K). Interestingly, phosphorylation by both kinases together yielded all of the phosphoforms of stathmin identified so far. Two-dimensional phosphopeptide analysis allowed us to demonstrate that the same four sites were exclusively found to be phosphorylated in vivo, in brain tissue as well as in control or nerve growth factor-stimulated PC12 cells. In this latter case, the major site phosphorylated in response to nerve growth factor being serine 25, it is likely that a kinase such as a mitogen-activated protein kinase, known to be activated by growth factors, might directly phosphorylate stathmin. The phosphopeptide map analysis allowed further identification of the specific combinations among the four sites whose phosphorylation is responsible for the characteristic two-dimensional polyacrylamide gel electrophoresis migration of the resulting stathmin forms both in vitro and in vivo and revealed the existence of likely structural interactions between the sites phosphorylated. In conclusion, our results show that phosphorylation of serines 16, 25, 38, and 63 accounts for all of the major functional stathmin forms observed in vivo. The present identification of these sites will foster a better understanding of some intracellular mechanisms involved in the diverse physiological regulation of the proliferation, differentiation, and functions of cells, including the role of stathmin in these processes as a relay integrating diverse signaling pathways.

Amino Acid Sequence↗
PubMed1993

Mapping of the gene for interferon-inducible dsRNA-dependent protein kinase to chromosome region 2p21-22: a site of rearrangements in myeloproliferative disorders.

Recent evidence suggests that the human interferon-inducible double-stranded RNA-dependent protein kinase may function as a tumor suppressor. Here we describe the mapping of the gene for this kinase to chromosome region 2p21-22 by fluorescence in situ hybridization. A combined analysis of cytogenetic data from a series of 341 patients with hematologic disorders that exhibited cytogenetic abnormalities and from published reports indicates that abnormalities involving 2p21-22 occur nonrandomly and are observed among patients with acute myelogenous leukemia, raising the possibility of a role for this protein kinase in leukemogenesis.

Bone Marrow↗