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Biomedical subjects

M Masini

Publications and source records attributed to M Masini.

At least 37 records · Page 2Linked to original sources
PubMed1996

GRK2 and beta-arrestin 1 as negative regulators of thyrotropin receptor-stimulated response.

Arrestins are regulatory proteins for a number of G-coupled receptors. The binding of arrestin to receptor phosphorylated by G protein-coupled receptor kinase (GRK) quenches the activation of the G protein, thus resulting in receptor homologous desensitization. We have previously shown that the levels of beta-arrestin1 are regulated by intracellular cAMP and proposed that this may represent one homeostatic mechanism with which to regulate some cellular responses. To test this hypothesis, we focused on the TSH receptor using a rat thyroid cell line, FRTL5. We found that beta-arrestin1 is the only detectable isoform of arrestin expressed in FRTL5 and that its expression is regulated by TSH. To investigate the possible role of GRK2/beta-arrestin1 machinery in the mechanism of TSH receptor homologous desensitization, we used a cotransfection approach. The TSH-induced cAMP accumulation in COS7 cells transfected with TSH receptor was reduced by 35-45% when cotransfected with GRK2 and/or beta-arrestin1, indicating that the TSH receptor can be regulated by a GRK/arrestin mechanism. This raised the hypothesis that TSH increases the levels of beta-arrestin1, which in turn could regulate the TSH stimulation. To test this point a FRTL5-derived cell line overexpressing beta-arrestin1 was generated. In these cells the TSH-stimulated cAMP accumulation and, more importantly, the mitogenic activity were substantially blunted. Our results show that TSH receptor-stimulated cAMP accumulation and cell proliferation can be controlled by a GRK2/beta-arrestin1 mechanism.

Animals↗
PubMed1996

[Spinal cord schwannoma: case report].

The intramedullary localization of schwannomas is rare, corresponding to 0.3% of all intraspinal tumors. The authors report the case of a 52-year-old white female patient that presented with symptoms of spinal compression by the presence of an intramedullary schwannoma at the level C4-C6. There were no symptoms of neurofibromatosis, entity frequently related to the lesion. The magnetic resonance imaging examination and the per-operatory biopsy were decisive factors in planning and executing the treatment, by establishing the characteristics, location and diagnosis of the lesion. Its delimitation and posterior location have facilitated total surgical exeresis. The transoperatively histopathologic examination allowed adequate surgical procedure. The Schwann cell is not found normally in the central nervous system and its presence in this site has been subject of many theories exposed in this paper, which proposes comprehensive review of the clinical aspects, imaging diagnosis, pathology, differential diagnosis and treatment of schwannomas. It is probable that, with the advances verified in the available diagnostic methods, a greater number of these lesions may be diagnosed in the future.

Diagnosis, Differential↗
PubMed1995

The regulation of liver protein degradation by aminoacids in vivo. Effects of glutamine and leucine.

The effects in vivo of the two major in vitro regulatory aminoacids, leucine and glutamine, on liver protein degradation were explored in male young adult Sprague Dawley rats. Protein degradation was stimulated by the injection of the antilipolytic drug 3,5 dimethylpyrazole (DMP), which rises glucagon and lowers insulin plasma levels. At the appropriate time-points (20 and 40 min) after the injection of DMP, glutamine or leucine (12.5 mg/kg b.w.) were injected intraperitoneally. The rate of liver protein breakdown was evaluated 60 min after the injection of DMP on the basis of the release of valine into the perfusate during a short term single pass liver perfusion. The aminoacid was assayed by an HPLC procedure. Results show that the administration of glutamine inhibited the DMP-induced increase in the rate of valine release from the perfused liver whereas the administration of leucine did not; neither of the aminoacids appeared to have any effect on the metabolic or endocrine changes that are required for the induction of liver autophagy and protein breakdown by DMP. It is concluded that the aminoacid glutamine has a powerful action on the in vivo regulation of liver protein breakdown, which is not apparent with leucine.

Animals↗
PubMed1994

Spinal cord injury: patients who had an accident, walked but became spinal paralysed.

Out of 1410 patients admitted to the spinal cord injury unit (SARAH) for rehabilitation during a 10-year period (1981-90) 10 had a missed spinal trauma lesion and became paralysed after having overcome the initial injuries and being allowed to walk. Patients were admitted to hospital with a history of being able to walk after an accident and subsequently developing a neurological deficit. Seven patients had radiological findings compatible with instability of the spine. Four had a head injury with coma and an undetected spinal fracture at the first evaluation in the emergency room. Other associated factors were: spinal stenosis, prolapsed disc, infection, foreign bodies, procedures for reduction and stabilization of the fractured spine. We emphasize the need for very careful clinical study and investigation for the diagnosis of multiinjured patients, especially when there is a concurrent brain injury.

Accidents↗
PubMed1994

Endocrine and amino acid regulation of liver macroautophagy and proteolytic function.

Regulation of liver macroautophagy and protein degradation by hormones and direct regulatory amino acids were studied in male 2-mo-old Sprague-Dawley albino rats with the use of the antilipolytic agent 3,5'-dimethylpyrazole (DMP; 12 mg/kg body wt ip) as a stimulatory agent. Injection of DMP decreased glutamine plasma levels and glutamine release from the perfused liver. Autophagic vacuoles were observed in the pericanalicular area of liver cells after 30 min. Levels and release of other regulatory amino acids did not exhibit any significant decrease but subsequently increased. Intraperitoneal administration of glutamine inhibited the proteolytic response. In conclusion, these studies demonstrate that in vivo induction and control of liver macroautophagy and protein degradation by the physiological mechanism (i.e., by shortage of nutrients) involve unbalanced and asynchronous changes in the levels of selected direct regulatory amino acids (i.e., a decrease in glutamine and a subsequent increase in leucine and tyrosine levels).

Amino Acids↗
PubMed1993

Molecular analysis of human beta-arrestin-1: cloning, tissue distribution, and regulation of expression. Identification of two isoforms generated by alternative splicing.

The cDNA for human beta-arrestin-1 was cloned by polymerase chain reaction (PCR) and identified based on its remarkably high amino acid identity (98.6%) with the bovine sequence. Two alternatively spliced isoforms of human beta-arrestin-1, differing only in the presence or absence of 24 base pairs/8 amino acids within the sequence, were identified and called beta-arrestin-1A and beta-arrestin-1B, respectively. Both isoforms were found in all tissues tested. Southern blot analysis revealed the existence of a single gene for beta-arrestin-1, suggesting that the two isoforms are generated by alternative mRNA splicing. The possible presence of similar isoforms was investigated for the other members of the arrestin/beta-arrestin gene family by PCR. Two isoforms of arrestin were revealed in bovine peripheral blood leukocytes. The expression of beta-arrestin-1 was studied in several human tissues and cell types. High levels of beta-arrestin-1 mRNA and immunoreactivity were found in peripheral blood leukocytes. The possible regulation of the expression of beta-arrestin-1 was also investigated. Our work documents for the first time that the expression of beta-arrestin-1 is modulated by intracellular cAMP. Using two cell types, human endothelial cells and smooth muscle cells, we found that 6-8-h treatments with the cAMP-inducing agents cholera toxin, forskolin, iloprost, and isoproterenol raised beta-arrestin-1 mRNA by 2-4-fold. Forskolin preferentially increased beta-arrestin-1A expression in smooth muscle cells, as assessed by PCR. beta-Arrestin-1 immunoreactivity was 2-3-fold higher in smooth muscle cells exposed to forskolin for 8 h, compared with untreated controls. We conclude that (i) the finding of alternatively spliced isoforms of beta-arrestin-1 and arrestin documents a novel mechanism to generate diversity within the arrestin/beta-arrestin gene family; (ii) the abundant expression of beta-arrestin-1 in peripheral blood leukocytes further supports our previous suggestion of a major role for the beta ARK/beta-arrestin system in regulating receptor-mediated immune functions; (iii) the increased expression of beta-arrestin-1 by cAMP suggests a new mechanism for the regulation of receptor-mediated responses.

Alternative Splicing↗
PubMed1993

A new method for the investigation of endocrine-regulated autophagy and protein degradation in rat liver.

The effect of the antilipolytic agent 3,5-dimethylpyrazole (DMP) on liver autophagy and protein degradation was studied on male young adult rats (200 g body wt) of the Sprague-Dawley strain by electron microscopy and short-term single-pass liver perfusion and HPLC amino acid assay in the perfusate. Treatment with DMP (12 mg/kg body wt) enlarged the lysosomal-autophagic compartment in liver cells in 30 min and increased significantly the concentrations of valine and total amino acid in blood plasma (taken at sacrifice) and valine concentration in the liver perfusate in 60 min. These effects of DMP stimulating liver were secondary to the metabolic and endocrine effects of the drug (which caused a decrease in FFA, glucose, and insulin and an increase in glucagon and corticosterone plasma levels with a shorter latency, about 15 min). The effects of DMP were compared to those of other treatments inducing liver autophagy and protein degradation in vivo. Alterations after DMP or glucagon injections were similar, but they were larger and lasted for a longer time with DMP administration. Treatment with vinblastine or chloroquine enlarged the lysosomal-autophagic compartment without increasing protein breakdown.

Amino Acids↗
PubMed1992

Prevalence of antibodies against hepatitis C virus in a dialysis unit.

Anti-HCV was tested in 77 uremic patients, 48 on hemodialysis (HD), 29 on CAPD, by immunoenzymatic 1st and 2nd generation assays (ELISA I, II) and 4-antigen (4-RIBA) immublotting. The investigation was extended to the staff (n = 29) and to HCV-positive patients' families (n = 30). The prevalence using 2nd generation tests was double (21%) that in 1st generation tests (11%). A greater incidence in the HD than in the CAPD group (23 vs. 17%) and a highly significative correlation to dialytic age were observed. No one among the sanitary personnel and only 2 family members were found HCV positive, suggesting a low infectivity via the parenteral inevident route. Extracorporeal circulation and particularly the exposure time to the treatment seem to be the main risk factors.

Family↗
PubMed1991

[Paracoccidioidomycosis of intramedullar and cerebral localization].

It is reported our diagnosis and therapeutical experience with a patient that presented clinical, radiological and tomographical manifestations of paracoccidioidomycosis with involvement of lungs, brain and spinal cord. Besides being a rare case the authors call attention for the extreme difficulty in defining the final diagnosis, which was achieved only after laminectomy and surgical biopsy of the intra spinal cord tumor at the C5 level. The patient received two series of treatment with ketoconazole (400-600 mg/day). After both the patient presented tonic and clonic convulsive disorders. We speculated about a possible perigranulomatous inflammatory response related to the therapeutical intervention, not yet described in literature.

Central Nervous System Diseases↗
PubMed1991

[Atrial tachyarrhythmias in sinus node disease: diagnostic and therapeutic problems].

It is known that sinus node dysfunctions can, in some instances, be accompanied by paroxysmal supraventricular arrhythmias. It is however not completely understood if, in these patients, it is present a situation of electrical atrial vulnerability or an electrophysiological condition which may represent the substrate for these arrhythmias. With the aim to solve this issue, 23 patients with sinus node dysfunction (8 of whom with atrial tachyarrhythmias) underwent a complete electrophysiological study, according to the protocol of the Italian Group of Cardiac Electrophysiology. The results of the electrophysiologic study allowed to demonstrate that in 75% of patients with atrial tachyarrhythmias it was possible to reproduce the arrhythmia by means of a low aggressive protocol. Also, in these patients, an inter- and intra-atrial conduction disturbance was demonstrated and, with respect to those patients without arrhythmias, the atrial refractory period was shorter in basal conditions and during induced atrial rhythm with cycle length of 600 ms, it was longer in left atrium than in high right atrium, and it shortened to a lesser extent with the shortening of the cardiac cycle.

Anti-Arrhythmia Agents↗
PubMed1991

Exploring the mechanisms of in vivo regulation of liver protein breakdown in the rat by the use of the new antilipolytic-agent model.

In this study, we explored the changes in the rate of protein degradation in liver cells in vivo, using a method based on the physiological stimulation of liver autophagy. Male albino rats 1, 2, 6, 12 and 24 months old were fasted overnight, and then received an injection of the antilipolytic agent 3,5-dimethylpyrazole (DMP) to evoke a sudden shortage of lipid fuel. A comparison was made with the in vivo effects of glucagon by giving the 2-month-old group an intraperitoneal injection of this hormone. Samples of liver were taken after 0, 15, 20, 30, 60 and 150 min and processed for electron microscopy, and groups of rats were subjected to short-term single pass liver perfusion. Results show that in the younger age-groups, the DMP stimulation of liver autophagy and amino acid release is highly significant, and compares favourably with the glucagon model of induction of the autophagic process. With older rats, an age-related longer time-lag of the autophagic response and a decrease in the effect of DMP were observed. In conclusion, hormones may activate autophagy, whereas levels of plasma amino acids may tune down the process to adjust the availability of the substrate to tissue needs.

Amino Acids↗
PubMed1990

The brown adipose tissue of hyperthyroid rats. A biochemical and ultrastructural study.

Male Sprague-Dawley rats were treated with triiodothyronine (100 micrograms/100 g/day) for 2, 4, 7, 14 and 21 days and the biochemical and ultrastructural changes of the brown adipose tissue were investigated. Results showed that the tissue weight, DNA and phospholipid content increased very early (by day 2 or 4) and that triglycerides increased later. These hormonal effects are not inhibited by the beta 1-antagonist propranolol. From the morphological point of view, triiodothyronine administration induced the early proliferation and maturation of adipocyte precursors (interstitial cells and preadipocytes). It is concluded that triiodothyronine administration causes a very early hyperplasia in the brown adipose tissue similar to that observed during exposure to cold by mechanisms that may not be secondary to the involvement of norepinephrine.

Adipose Tissue, Brown↗
PubMed1990

Segmental mandibular regeneration by distraction osteogenesis. An experimental study.

We report the use of distraction osteogenesis for segmental mandibular regeneration. This technique has been used in thousands of patients in the Soviet Union to regenerate as much as 30 cm of tubular bone in the extremities. However, we are unaware of previous experimental or clinical reports of segmental mandibular regeneration by distraction osteogenesis. In a canine model, 2.5-cm segmental mandibular defects were filled with regenerate bone in 25 days at a rate of 1.0 mm/d using bifocal distraction osteogenesis. The diameters of the regenerate segments were comparable with preexisting mandible, and all animals resumed normal oromandibular function following regeneration. The regenerate bone was evaluated radiographically, angiographically, and histologically. In the control group without distraction osteogenesis, the segmental defects failed to fill with regenerate bone. The theoretical basis for distraction osteogenesis, a detailed description of the technique, and a review of previous studies on experimental mandibular lengthening are presented.

Animals↗
PubMed1990

Experience with a spinal cord unit in Brasilia, Brazil.

We have analysed our experiences in a Spinal Cord Unit in Brasilia, Brazil in the last 5 years (1982-1986). There were 738 outpatients and 243 inpatients. One hundred and six patients were operated on by the neurosurgical staff, and the indications for operation are discussed. Some patients showed neurological recovery with surgery and some without surgery. Patients with a complete neurological deficit on admission did not show any improvement, and those with a severe but incomplete deficit showed improvement with surgery (18%), which was better than those without an operation. We conclude that a surgical procedure seems to be indicated in those with a comminuted, or with an unstable fracture, if there is an incomplete neurological deficit with an unreduced spinal deformity. There was a possibility of recovery of some nerve root function. The goal of surgical treatment is to restore and maintain the anatomical relationships between the spinal canal, spinal cord and nerve roots with the simplest possible surgical procedure, returning the patient as soon as possible to his functional capacity and social life.

Activities of Daily Living↗
PubMed1990

[Comparison of lidoflazine and quinidine in the conversion to sinusal rhythm in atrial fibrillation of recent onset].

In order to compare the efficacy of oral lidoflazine (240 mg/die) and oral quinidine (1200 mg/die) in re-establishing sinus rhythm, we studied 115 patients (mean age 63.8 years; range 32-91) with atrial fibrillation of recent onset (less than 3 months). Patients with cardiac failure, acute myocardial infarction, severe intraventricular conduction disturbances, kaliemia less than 3.8 mEq/L or digoxinemia greater than 2 ng/ml were not included. Patients were randomly given one of the 2 drugs, until conversion to sinus rhythm was achieved, severe side effects occurred or for a maximum therapy of 5 days. No significant differences were present between the 2 groups in terms of age, male/female ratio, duration of atrial fibrillation, presence of an enlarged left atrium, presence of organic heart disease (or arterial hypertension) or digitalis therapy. Sinus rhythm resumption was obtained in 41/58 (71%) patients treated with quinidine and in 47/57 (82%) patients treated with lidoflazine (p = ns). In successful cases, the mean treatment time was 79 +/- 33 (SD) hours for quinidine and 66 +/- 36 hours for lidoflazine (p = ns). Both drugs showed the same efficacy in 3 subgroups of patients in whom the arrhythmia had different duration (less than 24 hours; between 24 hours and 3 days; more than 3 days). Treatment was stopped in 5 patients receiving quinidine (gastrointestinal side effects) and in 3 patients receiving lidoflazine (frequent premature ventricular beats in 2 and polymorphic ventricular tachycardia of the "torsade de pointes" type in 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Prognostic importance of dipyridamole-echocardiography test in coronary artery disease.

We studied the value of dipyridamole-echocardiography test in comparison with clinical, resting electrocardiogram and echocardiogram variables in predicting cardiac events occurring in 539 consecutive patients referred for dipyridamole-echocardiography test from 1984 to 1987. There were 118 cardiac events: 11 cardiac deaths, 12 nonfatal myocardial infarctions, and 95 coronary revascularization (bypass or angioplasty) procedures. A Cox survival analysis identified echocardiographic positivity after dipyridamole administration as the best predictor of cardiac events (relative risk ratio, 2.7). The next most powerful predictor was angina after dipyridamole administration (relative risk ratio, 1.9). Cardiac events occurred in 14 (6%) of 253 patients with normal high-dose dipyridamole echocardiographic test results, in 21 (26%) of 82 patients with high-dose dipyridamole echocardiographic positivity (0.84 mg/kg during 10 minutes), and in 83 (41%) of 204 patients with low-dose dipyridamole echocardiographic positivity (0.56 mg/kg during 4 minutes) (p less than 0.0001). In a subset of 341 patients, exercise electrocardiography stress test and coronary angiography were also available. A Cox survival analysis again identified echocardiographic positivity after dipyridamole as the best predictor of cardiac events (relative risk ratio, 1.9) followed by a pathologic coronary arteriography (relative risk ratio, 1.2). We conclude that the presence and timing of a transient dyssynergy during dipyridamole stress are useful predictors of subsequent cardiac events.

Actuarial Analysis↗
PubMed1989

Transmitral flow changes during dipyridamole-induced ischemia. A Doppler-echocardiographic study.

Myocardial ischemia results in altered left ventricular (LV) diastolic compliance, reflected by an abnormal mitral inflow pattern on Doppler echocardiography. To investigate the relationship of Doppler echocardiography and regional myocardial systolic function during dipyridamole infusion, we evaluated transmitral flow changes detected by pulsed Doppler technique during a high-dose dipyridamole echocardiography test (DET, two-dimensional echo monitoring with dipyridamole infusion, up to 0.84 mg/kg over 10 min). The DET response produced two groups: group 1 (34 patients) with negative DET, and group 2 (35 patients) with positive DET, defined as the development of a newly onset LV regional asynergy. The E/A values overlapped at baseline (1.07 +/- .32 vs .92 +/- .22; p = NS) but differed at peak changes (.92 +/- .26 vs. 75 +/- .25; p less than .01). Heart rate changes could not account for the observed Doppler changes, since the values of R-R interval were similar in the groups, both basally (.927 +/- .226 vs .867 +/- .143 s; p = NS) and at peak dipyridamole (.754 +/- .100 vs. 681 +/- .112; p = NS). Transient myocardial ischemia induced by dipyridamole administration is accompanied by changes in transmitral flow, which consist of an increase in the relative atrial contribution to LV filling, possibly owing to an acute impairment in LV relaxation.

Adult↗