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Biomedical subjects

M Ferrari

Publications and source records attributed to M Ferrari.

At least 127 records · Page 7Linked to original sources

A genetic linkage study of schizophrenia to chromosome 5 markers in a northern Italian population.

Some recent findings report that the area 5q11.2-13.3 of chromosome 5 segregates with schizophrenia in an uncle-nephew pair (Bassett et al 1988). However, linkage studies between chromosome 5 markers loci and schizophrenia lead to different results: Sherrington et al (1988) found a positive linkage, whereas other groups of researchers found evidence against linkage (Kennedy et al 1988; St. Clair et al 1989; Detera-Wadleigh et al 1989; McGuffin et al 1990; Aschauer et al 1990; Crowe et al 1991). We have studied five Italian pedigrees segregating schizophrenia using a map of four markers for the chromosomal region 5q11.2-13.3. Linkage analyses revealed negative lod scores, and thus no evidence for linkage was obtained in our Italian families.

Chromosome Mapping

Whole rat electron paramagnetic resonance imaging of a nitroxide free radical by a radio frequency (280 MHz) spectrometer.

Low frequency (280 MHz) electron paramagnetic resonance spectroscopy has been used to follow uptake, distribution and reduction of the nitroxyl spin label PCA in the rat. No difference of half life was found in seven rats submitted to three administrations of PCA (11.3 +/- 0.4; 11.0 +/- 0.6 and 11.5 +/- 0.7 min). Transversal two-dimensional images of PCA distribution in the rat body were obtained over 6 min by means of field gradients. PCA was observed in three regions by projections along the longitudinal axis of the rat. PCA accumulation was found in the lower abdomen 12 min after the start of the PCA injection.

Animals

Excimer laser intrastromal keratomileusis.

We studied 30 eyes in 22 patients with severe myopia who underwent myopic keratomileusis combined with excimer laser refractive correction. The goals of the study were to evaluate the efficacy of the procedure in decreasing myopia, to assess the response of the cornea to intrastromal photoablation, and to examine the relationship between the number of laser pulses and the refractive correction achieved. The patients were observed for six months. The technique demonstrated a marked refractive reduction (from 171.875 +/- 3.32 diopters to -2.125 +/- 1.40 diopters) and an excellent corneal response to photoablation. An average decrease of 7.63 diopters was observed in keratometry readings. No marked change in the degree of astigmatism was observed after the procedure. Intrastromal haze was observed biomicroscopically in three of 30 eyes (10%). Postoperative best-corrected visual acuity remained at the preoperative level in 22 eyes (74%), improved in five eyes (16%), and declined in three eyes (10%). At the end of the follow-up period, uncorrected visual acuity was 20/50 or better in three of 30 treated eyes (10%) and 20/100 or better in 25 of 30 treated eyes (83.3%). No intraoperative complications were observed, but the following postoperative complications were seen in seven of 30 (23.2%) eyes: four eyes (13.3%) developed irregular astigmatism, one eye (3.3%) had poor night vision, and two eyes (6.6%) had irregularities in Bowman's membrane. The operation was repeated with homoplastic material in one of the two eyes with Bowman's membrane irregularities after six months, because of central alterations in Bowman's membrane.

Adolescent

Iron-induced ascorbate oxidation in plasma as monitored by ascorbate free radical formation. No spin-trapping evidence for the hydroxyl radical in iron-overloaded plasma.

A study was made of the interaction of plasma ascorbate and ascorbate free radical (AFR) with exogenously added iron. The quantitative determination of AFR has the advantage that transient increases in ascorbate oxidation can be directly monitored by e.p.r. spectroscopy. An AFR signal was found in the plasma of all donors and was unaffected by superoxide dismutase, catalase and the strong iron chelator deferoxamine. These findings and the rapid decrease in AFR under a nitrogen atmosphere suggest that plasma AFR is probably a result of air auto-oxidation. Iron loading of plasma did not affect the intensity of the AFR signal until the iron concentration approached or exceeded the plasma latent iron-binding capacity. In iron-overloaded plasma, the intensity of the AFR signal increased to about 10 times the normal level before decreasing rapidly to undetectable levels after 15-20 min. Determination of plasma ascorbate showed that the disappearance of AFR was due to a complete loss of the vitamin. When 50 microM-ascorbate was loaded with iron in iso-osmotic phosphate buffer there was an increase in the AFR signal, independent of the iron concentration, which was stable at least for 15 min. Thus the rate of ascorbate loss in the iso-osmotic phosphate buffer was considerably lower than in iron-overloaded plasma. The addition of different iron chelators produced comparable effects on the intensity of the AFR signal in both iron-overloaded plasma and ascorbate solution. These results suggest that the characteristic behaviour of plasma AFR after iron loading is due to its specific iron-binding capacity and to plasma ferroxidase activity. The ferroxidase activity of plasma is important to promote the transfer of Fe2+ into transferrin without a transient ascorbate oxidation. Spin-trapping studies with 5,5-dimethyl-1-pyrroline N-oxide and N-t-butyl-alpha-phenylnitrone revealed that iron-overloaded plasma was unable to produce spin-trap adducts even in the presence of 50-300 microM-hydrogen peroxide or 100 microM-azide. Evidence of OH. radical formation was obtained only after the addition of EDTA. Therefore, iron-overloaded plasma itself does not produce a Fenton reaction and, if ascorbate does indeed have a free-radical-mediated pro-oxidant role, it is not detectable in plasma by spin-trapping experiments.

Ascorbic Acid

Molecular characterization of hemoglobin C in Sicily.

Analysis of polymorphisms of the beta-globin gene cluster was performed on 12 families and on one unrelated individual of Sicilian origin who carried hemoglobin C (Hb C). Two different haplotypes were found in association with beta c Sicilian alleles, corresponding to haplotypes I and II previously described in American blacks. In our population, the more frequent one (haplotype I) was linked to the lack of a polymorphic HpaI site 3' to the beta gene (13.0-kb fragment), similarly to haplotype I in blacks, while the less frequent one was linked to a 7.0-kb HpaI fragment attributable to a site that had never been previously described in linkage with beta c alleles. In Italy, these two haplotypes have been found in rare cases in association with beta A alleles. These findings provide new insights into the origin of Hb C present in Sicily, suggesting that (1) the beta c mutation detected in Sicily derived from African black chromosomes and does not represent a new mutation; and (2) Hb C may have originated either by multiple mutational events on separate chromosomes or by mutation in the HpaI site 3' to the beta gene in a pre-existing beta c chromosome.

Alleles

Four new mutations of the CFTR gene (541delC, R347H, R352Q, E585X) detected by DGGE analysis in Italian CF patients, associated with different clinical phenotypes.

The delta 508 mutation accounts for about 53% of the molecular defects causing cystic fibrosis (CF) in Italy. The numerous additional mutations detected so far are all relatively rare, and about 30% of CF chromosomes carries unknown mutations in our patients. In order to identify the non-delta F508 mutations causing CF in our population, we performed GC-clamped denaturing gradient gel electrophoresis (DGGE) on 9 exons of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in a sample of 86 Italian CF patients carrying unknown mutations on at least one chromosome. Direct sequencing of 17 samples showing an altered electrophoretic mobility allowed the identification of four new mutations (541delC, R347H, R352Q, and E585X), five mutations already known (G85E, I148T, G178R, 1078delT, and R347P), and one rare variant (1898 + 3A-->G). The strategy based on GC-clamped DGGE represents an efficient and rapid approach for mutation detection for those genetic diseases, such as CF, in which a large number of rare molecular defects has been described.

Base Sequence

Muscle oxygenation by fast near infrared spectrophotometry (NIRS) in ischemic forearm.

Fast scanning near infrared spectroscopy (680-1050nm) was utilized to evaluate human forearm muscle oxygenation in 15 adults volunteers. Spectra were recorded in hypoxic hypoxia, ischemia and venous outflow restriction. Derivative spectra were performed with the aim to obtain a quantitative information of Hb/Mb oxygen saturation free from volume and scattering changes. The absorption spectra O.D. demonstrate an increase of deoxy-Hb/Mb in hypoxic condition with a moderate volume changes. In ischemia a rapid Hb/Mb desaturation occurred until a plateau was reached at 4th min. The cuff release was followed by hyperemia with Hb volume raise and oxy-Hb/Mb increase above the control. Spectral data support the hypothesis that derivative NIRS can be used to identify muscle oxygenation changes.

Adult

Immunodepressive activity of FCE 23762 on humoral and cell-mediated immune responses in normal mice: comparison with doxorubicin.

FCE 23762 (3' desamino-3'[2(s)methoxyl-4-morpholinyl]doxorubicin) is a new doxorubicin (Dx) derivative that has been selected for clinical testing for its favourable antitumor characteristics, which include efficacy on Dx-resistant tumors. Immunosuppression is an undesirable side-effect of anti-cancer chemotherapy and the therapeutic efficacy of Dx is probably also related to its low immunotoxicity. It was, thus, of interest to compare the effects of FCE 23762 and its parental drug on the immune responses. Both compounds were injected i.v. into healthy mice at equitoxic doses and according to different treatment schedules. Single doses of FCE 23762 and Dx, given concomitant or after the antigen, suppressed at the same degree and dose-dependently the primary anti-SRBC antibody response. Following a multiple treatment schedule after the antigen, FCE 23762 was less suppressive than Dx on both primary and secondary antibody production. Differently from Dx, that was completely inactive, FCE 23762 moderately inhibited DTH reaction to SRBC, only at the highest single dose tested or for repeated administrations given simultaneously or after priming. Both drugs were totally ineffective in delaying skin allograft rejection. Since spleen cellularity and ex vivo lymphocyte proliferation to Con A and LPS were similarly impaired by the two drugs, the differentiated immunodepressive activity of FCE 23762 and Dx cannot be merely associated to their cytotoxic and antiproliferative action. The hypothesis of a selective effect on different regulatory cell subsets and/or immune mechanisms is discussed.

Animals

Electrocardiographic changes in subarachnoid hemorrhage secondary to cerebral aneurysm. Report of 70 cases.

Electrocardiographic (ECG) alterations in the course of sub-arachnoid hemorrhage (SAH) have frequently been reported. The most frequent anomalies reported were lengthening of the QT interval, very negative or positive deep T waves, elevation or depression of the ST segment and the presence of U waves. We report 70 cases of SAH secondary to rupture of intracranial aneurysm (part of a larger group of 150) with ECG changes. We review the literature with particular regard to discussion of the possible pathogenesis of ECG changes and to the way they may affect the general clinical course.

Adult

Effects in calves of mixed infections with bovine viral diarrhea virus and several other bovine viruses.

The objective of this study was to verify whether a mixed infection in calves with bovine viral diarrhea virus (BVDV) and other bovine viruses, such as bovid herpesvirus-4 (BHV-4), parainfluenza-3 (PI-3) and infectious bovine rhinotracheitis (IBR) virus, would influence the pathogenesis of the BVDV infection sufficiently to result in the typical form of mucosal disease being produced. Accordingly, two experiments were undertaken. In one experiment calves were first infected with BVDV and subsequently with BHV-4 and IBR virus, respectively. The second experiment consisted in a simultaneous infection of calves with BVDV and PI-3 virus or BVDV and IBR virus. From the first experiment it seems that BVDV infection can be reactivated in calves by BHV-4 and IBR virus. Evidence of this is that BVDV, at least the cytopathic (CP) strain, was recovered from calves following superinfection. Moreover, following such superinfection the calves showed signs which could most likely be ascribed to the pathogenetic activity of BVDV. Superinfection, especially by IBR virus, created a more severe clinical response in calves that were initially infected with CP BVDV, than in those previously given the non-cytopathic (NCP) biotype of the virus. Simultaneous infection with PI-3 virus did not seem to modify to any significant extent the pathogenesis of the experimentally induced BVDV infection whereas a severe clinical response was observed in calves when simultaneous infection was made with BVDV and IBR virus.

Animals

An experimental contribution to the study of the pathogenesis of bovine viral diarrhea virus infection.

This presentation summarizes the results of a study on the pathogenesis of bovine viral diarrhea (BVDV) infection. The cytopathic (CP) strain TVM-2 of BVDV induced in calves an overt clinical disease which is usually recorded as the acute primary BVDV infection observed under natural conditions. In contrast the non-cytopathic (NCP) strain New York-1 of BVDV did not cause any significant signs of disease. However, when the calves were immunosuppressed by treatment with dexamethasone (DMS) the biotype of BVDV involved did not seem to be as important as it appeared to be in an immunologically normal animal. This was shown in this study by the NCP BVDV which caused a fatal disease in calves treated with DMS. A mixed infection given to calves by injecting them with both CP and NCP BVDV, did not result in any particularly serious disease. So, the potential immunosuppressive activity of BVDV itself for the host has not been proven under the experimental procedures used in this experiment. Finally, a modified-live CP BVDV vaccine was unable to cause clinical disease when injected into calves that had been infected previously with strain New York-1 of BVDV.

Animals

A tissue culture vaccine with lapinized chinese (LC) strain of hog cholera virus (HCV).

The lapinized chinese (LC) strain of hog cholera virus (HCV), was adapted to grow in a cell line from minipig kidney (MPK) where it reached a titer, as determined by immunofluorescence, significantly higher than in rabbits. Inasmuch as the immune serum to HCV neutralized the culture-adapted virus, it was concluded that its antigenicity did not undergo any change after adaptation to MPK cells. The MPK-LC adapted virus (MPK-LC-HCV) showed also a higher immunogenic activity in rabbits, in comparison with the original LC virus. The MPK-LC-HCV protected pigs against challenge infection with virulent HCV. Thus, the vaccinated pigs did not show any clinical signs of disease, nor have they been responsible of virus shedding after they were exposed to the challenge infection 1 month or 6 and 11 months later. All vaccinated pigs seroconverted after vaccination and the antibody titers were on the same range of those reported in pigs vaccinated with the traditional vaccine prepared in rabbits. In the same pigs the antibody concentration underwent a booster effect following challenge infection. It was suggested the MPK-LC-HCV vaccine as an alternative product that might be used to prevent HCV infection. prevent HCV infection.

Animals

Protective effects of the Hemopump left ventricular assist device in experimental cardiogenic shock.

The efficacy of the new cable-driven rotating left ventricular assist device Hemopump in cardiogenic shock was examined in experiments with adult sheep (n = 14; body weight 50-71 kg). Shock was induced by high frequency ventricular pacing. Aortic, pulmonary, central venous and left ventricular pressures as well as electromagnetic measurements of coronary blood flow were recorded continuously; cardiac output was measured by thermodilution technique. Blood samples for determination of oxygen content, electrolytes and lactate were taken under control conditions, in shock, and during pump intervention at different levels of pump speed. Vascular resistance, total body and myocardial oxygen consumption as well as myocardial uptake and release of lactate were calculated. High frequency pacing led to a significant decrease in cardiac output (from 3.8 +/- 0.8 to 2.2 +/- 1.6 l/min), mean aortic pressure (89.1 +/- 14.4 to 47.6 +/- 7.2 mmHg), and total body oxygen consumption (2.6 +/- 0.3 to 1.4 +/- 0.7 ml/min per kg), as well as myocardial release of lactate (arterial coronary-venous difference of lactate: 0.27 +/- 0.26 to -0.32 +/- 0.72 mmol/l). Hemopump assist in this condition resulted in a significant increase in cardiac output (to 2.8 +/- 0.6 l/min), mean aortic pressure (to 65.6 +/- 13.9 mmHg), and myocardial perfusion pressure (from 25.5 +/- 11.0 to 59.0 +/- 14.7), and led to nearly normal total body oxygen consumption (2.5 +/- 0.7 ml/min per kg), a decrease in myocardial oxygen consumption (from 6.1 +/- 2.1 in shock, to 4.8 +/- 1.7 ml/min per 100 g), and to normal arterial coronary-venous difference of lactate (0.24 +/- 0.26 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Excimer laser intrastromal keratomileusis: case reports.

We report the results in six eyes on which we performed a new surgical method: intrastromal corneal excimer laser photoablation following lamellar corneal keratectomy with a microkeratome. The study was designed to evaluate the clinical and refractive efficacy of the procedure, to assess the behavior of the cornea following stromal photoablation, and to evaluate the relationship between the number of laser pulses and the decrease of myopia. The technique demonstrated an excellent corneal response to photoablation but a poor refractive predictability.

Adult

Determination of lorajmine and its metabolite ajmaline in plasma and urine by a new high-performance liquid chromatographic method.

Lorajmine is a monochloroacetyl derivative of ajmaline with electrophysiological properties somewhat different from those of the compound of origin. Since lorajmine is rapidly hydrolyzed to ajmaline by plasma and tissue esterases, it is crucial to measure plasma levels of both drugs separately. A major problem in assaying lorajmine is its chemical instability in plasma both after blood sampling and during the extraction procedure. Furthermore, lorajmine (unlike ajmaline) is not fluorescent and has a very low UV absorbance, so the standard detectors for high-performance liquid chromatography cannot be used. We describe a new method that solves the problems of instability and sensitivity. Plasma esterases are first blocked pharmacologically (neostigmine); ajmaline is then measured by direct on-column injection of samples. Last, lorajmine is completely converted to ajmaline, extracted, and measured with a fluorescence detector. The molar concentration of ajmaline obtained in the last step, minus that found by direct injection, gives the concentration of lorajmine. Some examples of pharmacokinetic applications are also given.

Administration, Oral