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Biomedical subjects

M Bossi

Publications and source records attributed to M Bossi.

At least 37 records · Page 2Linked to original sources

Modifications in a flexible surface loop modulate the isozyme-specific properties of mammalian alkaline phosphatases.

We have analyzed to what extent the surface loop domain of alkaline phosphatases (APs) is responsible for isozyme-specific functional properties. Unique AatII and RsrII restriction sites were introduced by site-directed mutagenesis at identical positions in murine tissue-nonspecific AP (TNAP) and human placental AP (PLAP) cDNAs to allow the homologous exchange of the loop domain of the TNAP (T domain) and PLAP (P domain) isozymes and the generation of the reciprocally chimeric molecules PLAP-T and TNAP-P. The introduction of the T loop into PLAP reduced the heat stability of PLAP-T to almost that of TNAP. The domain substitution was accompanied by a conformational change that resulted in the loss of immune reactivity with four of 17 epitope-mapped anti-PLAP monoclonal antibodies. The T and P loops provided stabilization to the side chain of specific uncompetitive AP inhibitors. The introduction of the T domain also conferred collagen-binding properties to PLAP-T accounting for half of the binding affinity of TNAP for collagen, while not affecting PLAP binding to IgG. Our data indicate that the surface loop determines overall enzyme stability, differs conformationally in the various isozymes, and modulates catalytic parameters in the presence of protein ligands, thus, accounting in part for isozyme-specific protein interactions.

Alkaline Phosphatase↗

Pregnancy-associated plasma protein B (PAPP-B): isolation from human late pregnancy serum and biochemical characterization.

The pregnancy associated plasma protein B (PAPP-B) was first described by Lin et al. as a glycoprotein with a molecular weight of about 1,000 kD and a serum half life of less than 24 hours after delivery. We isolated PAPP-B from late pregnancy serum using liquid chromatography including HPLC. PAPP-B was found to be a glycoprotein with a molecular weight of 1,300 kD and to be an octadecamer of identical subunits (74 kD each). Cleavage of the carbohydrates with trifluoromethanesulfonic acid reduced the molecular mass to 65 kD (by SDS PAGE, 12.2%). Isoelectrofocusing and titration curves fixed the isoelectric point at 5.3. Spectroscopy measurements between 230 and 360 nm yielded a trp/tyr ratio of 1.1. Amino acid analysis showed that each subunit contained five methionines; this was confirmed by a CNBr cleavage experiment.

Chromatography, High Pressure Liquid↗

Reflex cardiovascular control in congestive heart failure.

This article reviews evidence that the reflex control of the cardiovascular system provided by negative feedback mechanisms is impaired in congestive heart failure (CHF). The impairment involves vagal and sympathetic modulation of the heart exerted by arterial baroreceptors. It also affects baroreceptor control of blood pressure and peripheral vascular resistance, as well as the cardiopulmonary receptor's ability to modulate sympathetic activity. The degree of such impairment is most marked in severe CHF but is also apparent, to a minor degree, in mild heart failure. Reflex impairment is due to a reduction in the receptor signal, but other factor under investigation are probably also involved. Digoxin and other pharmacologic treatments of CHF improve reflex function, thereby facilitating a reduction in the elevated sympathetic activity and a stepping up of the reduced vagal activity typical of CHF. This may be relevant to a patient's prognosis.

Animals↗

Synapsin I partially dissociates from synaptic vesicles during exocytosis induced by electrical stimulation.

The distribution of the synaptic vesicle-associated phosphoprotein synapsin I after electrical stimulation of the frog neuromuscular junction was investigated by immunogold labeling and compared with the distribution of the integral synaptic vesicle protein synaptophysin. In resting terminals both proteins were localized exclusively on synaptic vesicles. In stimulated terminals they appeared also in the axolemma and its infoldings, which however exhibited a lower synapsin I/synaptophysin ratio with respect to synaptic vesicles at rest. The value of this ratio was intermediate in synaptic vesicles of stimulated terminals, and an increased synapsin I labeling of the cytomatrix was observed. These results indicate that synapsin I undergoes partial dissociation from and reassociation with synaptic vesicles, following physiological stimulation, and are consistent with the proposed modulatory role of the protein in neurotransmitter release.

Animals↗

Functional evaluation 10 days and 3 weeks after acute myocardial infarction: comparative significance and prognostic value.

Early functional evaluation after non-complicated acute myocardial infarction (AMI) is widely recommended because of its prognostic value in the short term. In fact it seems to have a prognostic value within 15-20 days of the AMI, but in this period the patient is particularly controlled and is often still hospitalized. To evaluate the real significance of an early functional evaluation within 10 days of the AMI (mean 8.6 days +/- 1.2) as compared to an identical functional evaluation performed at 3 weeks after AMI (mean 20.16 days +/- 5.38) 25 patients with uncomplicated myocardial infarction were studied. Significant statistical differences were found between the first (ET1) and second (ET2) functional evaluations: they concern the maximal heart rate reached (P less than 0.001), the maximal pressure-rate product (P less than 0.05), the percentage increment of heart rate (P less than 0.01) and the total work performed (P less than 0.001). Agreement between ET1 and ET2 was found in 19 cases; 12 patients showed markers of ischaemia both at ET1 and ET2, while seven were free from ischaemia at both times. In six cases a disagreement between ET1 and ET2 was found: in particular, three cases had ischaemic ET1 and nonischaemic ET2; the reverse was seen in the other three. During follow-up (mean 215.4 days +/- 85.5), the total number of new events (reinfarctions, angina or surgery) among the 25 patients was eight; none occurred within the first 30 days after the AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[The emergency treatment of supraventricular tachyarrhythmias: the efficacy and safety of intravenous propafenone].

One hundred patients, admitted to the Emergency Unit for paroxysmal supraventricular tachycardia (SVT) with 1:1 AV conduction, atrial fibrillation (af) and flutter (AF) of recent onset (less than 72 hours) were treated with intravenous propafenone (P). The drug was administered at the dose of 70 mg over 5 min, repeated after 10 min if sinus rhythm (SR) was not restored and eventually followed by continuous infusion (0.35-0.50 mg/min) until conversion to SR or during the next 48 hours. Exclusion criteria were ventricular rate < 100/min, R-R intervals > 1 s, clinical signs of heart failure or asthma. Termination of SVT within 30 min was obtained in 94% of the patients, while reversion to SR occurred in 79% with af and in 55% with AF. For af and AF conversion was achieved within 30 min in 49% of overall responders (R), between 30 min and 6 hours in 27% and between 6 hours and 48 hours in 24%. The efficacy of P was significantly influenced by the duration of arrhythmia and left atrial size, measured by 2D-echocardiography. On the contrary, no difference was observed between R and non-R in mean age and in the percentage of primary or relapsing arrhythmias. Adverse effects were encountered in 7 patients: in 1 case worsened arrhythmia and in 6 patients, with long-lasting arrhythmias, congestive heart failure. Neither conduction disturbance nor extra-cardiac complications occurred. In conclusion, P provides effective and safe treatment for paroxysmal atrial tachyarrhythmias, so that it can be considered among the drugs of first choice even in non-intensive care units.

Adolescent↗

Heparin by alternative routes of administration.

In a study investigating the bioavailability of heparin administered by different routes, we also compared its bioavailability in the dog after oral administration of two enteric-coated formulations, one containing a heparin preparation (ITF-300) and the other sodium heparin. After administration of the formulation containing sodium heparin, there was no heparin in plasma, but when the formulation containing ITF-300 was given, plasma heparin levels were detectable.

Administration, Oral↗

[Acoustic, mechanical and electric alternans in heart tamponade. Clinical case and review of the literature].

The uncommon observation of alternation of the first heart sound in intensity, associated with mechanical and electric alternans is reported in a patient with cardiac tamponade due to large hemorrhagic pericardial effusion. Following pericardiocentesis and removal of 400 millilitres of fluid, all alternation phenomena disappeared. The combination of three alternation phenomena may be a helpful physical diagnostic sign of cardiac tamponade. The possible mechanisms of the "alternans" are discussed. It is suggested that variations in ventricular filling and emptying are the relevant pathogenetic factors.

Adolescent↗

[The Italian Group for the Study of Streptokinase in Myocardial Infarct: Evaluation of the enzymatic curve of creatine kinase].

Within the multicentre trial of the Italian Group for the Study of Streptokinase in Infarct (G.I.S.S.I.), a particular study was planned for the analysis of plasma creatine kinase curves (CK). Serial measurements of total plasma CK from 11,806 pts (5.905 treated with Streptokinase (SK) and 5,901 control pts (C)) were evaluated by the compartment method (Fig. 7), which is commonly used in pharmacological studies. By this method, the plasma enzyme curve is interpreted on the basis of the following kinetic parameters: the fractional rate of input (Ki) and of disappearance (Kd) of enzyme into and from the blood; the plasma cumulative CK activity (Dp); the time interval between the onset of symptoms and the beginning of the ascending CK curve (To); the time from To to the peak CK (Tp). The Dp/Ki ratio was employed for the estimate of myocardial infarct size. From the available data, acceptable CK curves could be derived in 7,632 cases (3,568 treated with SK, 4,064 control pts.). Compared with control group (Fig. 1--Tab. I) the SK treated pts presented increased Ki and Kd values and reduced To, (p greater than 0.001), Dp/Ki (p greater than 0.05). The earlier SK treatment was started, the higher difference (Fig. 2) was observed between the two groups (SK and C). No significant difference was found between the two groups (SK and C) with regard to sex (Fig. 3), age, history of previous myocardial infarct, re-infarction, early post-infarction angina. Statistically significant similar differences of the above parameters between SK and C groups, were also found when various infarct locations were considered, with the only exception of not-Q infarct (Fig. 4). In the cases complicated by pericarditis (Tab. II, Fig. 5), independently of treatment, reduced reperfusion related indexes and increased Dp/Ki ratio were observed. Severe left ventricular impairment (Killip class 4) tends to reduce (Tab. III) the differences in enzyme parameters between the two groups (SK and C). The patients who died (18 hours after the onset of symptoms) exhibited as the only significant difference compared to survivors the infarct-size related CK parameters (Dp/Ki), independently from the treatment. The mathematical model used in this study proved to be easily feasible and useful for the evaluation of the effect of the treatment in acute myocardial infarct.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical Trials as Topic↗

[Clinical and instrumental evaluation by multiple colonic manometry of tiropramide, trimebutine and octylonium bromide in irritable colon. II. Repeated oral administration].

Sixty out-patients with acute or sub-acute irritable colon were randomly allocated to receive 3 daily doses of 100 mg tiropramide, 150 mg trimebutine maleate or 20 mg octilonium bromide, orally during 5 consecutive days. Before and after treatment, multiple colonic manometry was performed, monitoring tonus, intensity and frequency of sinusoid contraction waves, transitories and vibrations, as well as the voluntary contraction capacity. Before treatment and after 2 and 5 days, the specific symptoms were also monitored, scored and recorded. Significant variations in tonus were not observed with any drug, but while tiropramide left unmodified the voluntary contractile ability, a significant inhibition was observed with trimebutine and, mainly, with octilonium. The overall power of spontaneous colonic contractions did not vary significantly with any drug. However, while with tiropramide a significant redistribution of muscular power was observed so as to increase propulsion waves and to decrease the ineffective transitory and vibrational contractions, with octilonium and trimebutine no clinically relevant redistribution of the power wasted in transient spasms was observed. Based on these observations, tiropramide was considered to be at least as effective an antispasmodic as octilonium and at least as effective a synchronizer as trimebutine, but was different from both reference drugs because it was the only one to act simultanously as both an antispasmodic and a synchronizer. The three drugs produced an improvement in each and all monitored symptoms as well as in the overall symptom intensity. Tiropramide, however, produced an improvement significantly faster, more progressively and to a greater extent than either reference drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

[The use of syntropium bromide as an antispasmodic].

The following trials were carried out to evaluate the antispasmodic effect of sintropium bromide in a group of 30 patients. The antispasmodic effect on the gastroduodenal system was observed endoscopically. The results were compared by means of double blind tests carried out using placebo and rociverine. The effect in a group of 10 patients was examined by X-ray of the digestive tract. The effect on another group of 20 patients suffering from abdominal colic was clinically evaluated. Sintropium bromide has a prompt anticholinergic action and for this reason may be used in the treatment of painful conditions of the bile, gastro-enteric and renal tracts, and also during the course of endoscopic examinations.

Bridged Bicyclo Compounds↗

[In-hospital and long-term prognosis in acute myocardial infarction. Comparative longitudinal study of 2 patient groups].

The in-hospital mortality, the causes of death, the actuarial survival curves were compared in two subsequent groups of patients admitted to our CCU for acute myocardial infarction: the first (group A) includes 791 pts, admitted from september '67 to december '72, the second (group B) includes 542 pts admitted from january '78 to june '80. The in-hospital mortality was significantly reduced in group B (A: 186/791, 23.5%; B: 72/542, 13,3%, p less than 0.01). This could be due to a reduction of the number of deaths for cardiogenic shock (A: 71/791, 9%; B: 30/542, 5.6%; p less than 0.01) and to reduction in the mortality rate for pulmonary oedema (from 6% to 1.5%, p less than 0.01), although the frequency of pulmonary oedema was the same during the two periods (A: 205 pts, 26%; B/156 pts 29%). We did not observe any significant difference in the long-term prognosis (54 months: A 79.3%, B 71.5%). The actuarial survival curves overlapped after the 1st semester after discharge. The most frequent cause of death during follow-up was a new myocardial infarction. None in the group A and only 3% in the group B were referred to the surgeon for coronary artery bypass grafting. We conclude that, in spite of a significant reduction of the in-hospital mortality, possibly related to the evolution in diagnosis and management of the disease, the long-term survival was not improved in a non-surgically treated population with myocardial infarction.

Adult↗

[An unusual cause of arterial and venous pulmonary hypertension].

A 49 year old woman with syphilis of recent onset was repeatedly admitted to the hospital on account of recurrent dyspnoea and hemoptysis. The symptoms and radiological signs indicated the presence of a "cardiac lung". The ECG disclosed right ventricular overload which was confirmed by echocardiography. The left heart was normal, not only on echocardiography but also on cardiac catheterization, which documented severe pulmonary hypertension, partly precapillary, partly postcapillary. The presence of chronic lung congestion in the absence of pathological findings pertaining to the left heart lead to the diagnosis of pulmonary venous occlusive disease. However, pulmonary angiography showed notable and widespread arterial amputations which are not present in this syndrome. Autopsy provided the correct diagnosis: sclerosing mediastinitis localized at the hilum with prevalent involvement of both arterial and venous pulmonary vessels.

Female↗