Biomedical subjects
Publications and source records attributed to L Rossi.
We have studied the IgG secreted in a system of CML. Microquantity of IgG (30-3000 micrograms/ml) of culture was determined using a fluorometric method based on the determination of the fluorescence derived by immune-complex IgG-FITC labeled goat Anti-human antibody to IgG covalently coupled to hydrophilic beads. This techniques has showed a good sensibility and accuracy.
The spectroscopic binding constant (visible absorption and EPR spectra) and the catalytic inhibition constant of N-3 and CN- were measured for bovine Cu, Zn superoxide dismutase chemically modified at all lysines by either succinylation or carbamoylation. These modifications partially inactivate the enzyme (10% and 50% residual activity respectively) but leave the native rhombic geometry of the copper site unaffected. It could thus be shown that the observed reduction of anion affinity of the lysines-modified proteins is related to the decreased positive charge of the protein.
The Cu,Zn superoxide dismutases from bovine and porcine erythrocytes and from yeast have been investigated with the aim to identify structural differences in relation to possible functional variability in this highly homologous class of protein. The isoelectric points of the bovine, porcine and yeast proteins were found to be 4.8, 5.8 and 4.5 respectively. According to these values the net protein charge, as evaluated by gel electrophoresis, varied more significantly for the porcine protein than for the other two proteins tested. The catalytic constants were found to be higher at pH = 7.6 than at pH 10.0 for all the three enzymes. This relative increase was much more pronounced in the case of the porcine enzyme. The KM value at pH = 10.0 was also significantly higher for the porcine enzyme. Since the spectroscopic properties of the active sites were identical for the three proteins, these results point to modulation effects by positively charged amino acid residues on the superoxide dismutase activity of these proteins, in a way that the resultant net charge of the protein seems to be as important as specific residues.
Gynecomastia developed in two epileptic patients some months after the addition of oral fluoresone 750 mg daily to the phenobarbital and phenytoin already being administered. The common systemic diseases that may give rise to gynecomastia were excluded. One of the patients presented hyperprolactinemia and a raised estrogen/androgen ratio but the hormone levels were not raised in the other. The onset of symptoms after fluorescence in both cases is highly suggestive, although the pathogenetic mechanism is not clear.
A study was carried out to establish whether the draft EEC method for determining overall (global) migration of the constituents of plastics-packaging materials into a fatty-food simulant could be applied to samples of commercially available homogeneous plastics materials and whether it would be possible to use extraction with a volatile solvent under appropriate conditions of time and temperature in cases where, for some reason, the fat test cannot be used. The results obtained show that the draft EEC method can be applied without insuperable problems to most commercially available homogeneous plastics-packaging materials. Moreover, taking into account the poor reproducibility and accuracy associated in some cases with global-migration tests in olive oil, the determination of global migration into isooctane (contact time 2 hr at 40 degrees C) seems to be a suitable substitute for determinations using exposure to olive oil for 10 days at 40 degrees C.
A group of 38 female and 39 male outbred Wistar rats were treated with 500 ppm technical-grade dichlorodiphenyltrichloroethane (DDT) in the diet and 500 ppm sodium phenobarbital (PB) dissolved in drinking-water for lifespan. Twenty-three of 29 (79.3%) female and 13/28 (46.4%) male surviving animals developed primary tumours which were detected starting at 65 weeks of age. Most of the liver tumours were neoplastic nodules, but well-differentiated hepatocellular carcinomas were also found in 3 males and 5 females of the exposed animals. No liver-cell tumour was observed in 59 rats exposed to a diet containing 3% olive oil.
Histologic examination of serial sections of the conduction system of the hearts of three young persons who died suddenly while engaged in active sports was performed. In no case were electrocardiogram tracings available. One patient, an 11-year-old girl, had micro-Ebstein's anomaly of the tricuspid valve associated with a septoseptal Kent fascicle through a wide gap of the central fibrous annulus and upper Mahaim fibers. Another patient, a 24-year-old football player, had a focal, 75 per cent obstructing atherosclerotic plaque in the proximal descending coronary artery, with scattered band necrosis and patchy myocardial fibrosis; upper and lower Mahaim fibers joined the atrioventricular node and the left bundle branch with the crest of the interventricular septum. The third patient, a 26-year-old cycling champion, had a conspicuous atrial fascicle of ordinary and transitional myocardium bypassing the atrioventricular node to anastomose with the His bundle (James accessory atrioventricular pathway). These findings indicate that atrioventricular conduction system abnormalities may play a fatal arrhythmogenic role in sudden death and raise questions regarding the prevention of electrical instability in young people engaged in active sports.
We have studied the carcinogenic effects of direct injection of benzo[a]pyrene (BP) and 6-methylbenzo[a]pyrene (BP6M) into fetal Swiss mice at 15 days of intrauterine growth. To determine the sensitivity of mouse fetuses to the action of ultimate carcinogens, benzo[a]pyrene-4,5-oxide (BPO) and a racemic mixture of 7 beta,8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene (BPDE), respectively, a proximal metabolite and an ultimate carcinogenic metabolite of BP, were also investigated in our system. The compounds were dissolved in acetone and trioctanoin (1:1) and injected at doses ranging from a minimum of 0.4 to a maximum of 19.8 nmol/fetus. Controls received 1 microliter/fetus of solvent. The experiment was terminated when the animals were 12-15 weeks old. On the basis of the percentages of lung adenomas and the average number of nodules/mouse, BPDE appears to be the most potent carcinogen of this group, causing 55% of tumors at a dose of 0.4 nmol and 73% at a dose of 4.0 nmol/fetus. At the dose of 0.4 nmol/fetus, neither BP nor BP6M induced tumors; injection of 4.0 or 19.8 nmol/fetus, caused incidences of 53% and 92%, respectively, in the case of BP6M and 24% and 39%, respectively, in the case of BP. BPO was not tumorigenic in this system, even at doses as high as 15.7 nmol/fetus. Eleven percent of the control animals had lung adenomas. The average number of nodules/mouse varied with the compound and the dose injected and closely followed the pattern of tumor incidence.
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A right-handed 32-year-old woman had recurrent combined partial temporal and secondary generalized epileptic states almost constantly related to menstruations. During such more or less prolonged episodes sometimes the patient presented right adversive attacks with short postictal dysphasia. The catamenial status epilepticus observed in this cas was manifested in two clear-cut behavioral phases. The first phase was characterized by frequently recurrent left temporal epileptiform discharges without tendency to diffusion, progressively more prolonged and pseudorhythmic associated with a signalized feeling of intense fear without apparent impairment of consciousness or speech disturbances. The electroclinical features of the first phase suggest a depth origin of the paroxysms, probably due to a primary epileptogenic focus in the left amygdaloid-hippocampal complex. In the second phase the left temporal focal semirhythmic discharges associated with fear bouts became more frequent and prolonged and began to be followed by long-lasting generalized discharges resulting in a trance-like state with severe impairment of consciousness. The diffuse paroxysmal activity regularly preceded by the left temporal focal discharges was interpreted as a form of secondary bilateral synchrony constantly triggered from a focal pacemaker represented by the primary epileptogenic focus. During the very short transient periods of sudden cessation of the epileptiform activity the patient returned immediately to an apparent normal mental state. Good correlation could be established between different seizure patterns and predominant clinical signs. Intravenous diazepam rapidly decreased and then completely stopped the catamenial status epilepticus. Some problems related to the classification of these rare epileptic events are discussed.
A total of 70 selected patients affected by reversible ischemic attacks in the vertebrobasilar system were studied. 50 patients presented transient ischemic attacks (TIA), while the other 20 patients suffered from 1-2 protracted transient ischemic attacks (PTIA). All patients underwent brainstem acoustic evoked potentials (BAEP) and electrooculography (EOG) 7-20 days from the last reversible ischemic attack, when all signs and symptoms completely disappeared. The combination of BAEP and EOG gave objective evidence of brainstem dysfunction in 61 out of 70 patients. BAEP resulted abnormal in 26 patients (16 TIA, 10 PTIA), EOG in 49 (36 TIA, 13 PTIA). Serial controls at 3, 6, and 12 months were conducted in 27 patients. 5 patients showed a normalization for BAEP and 7 for EOG 12 months after the first examination.
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The anti-anginal effect of oral verapamil was assessed in 12 patients with chronic effort-induced angina, using a single-blind, placebo-controlled protocol. The patients were given, in random order, placebo, verapamil 240 mg/day, verapamil 360 mg/day, for 24 hours, followed by a 24-hour washout period. Increase in tolerated work load, compared to a baseline bicycle exercise test, was -25 +/- 55.9 kgm/min on placebo, 137.5 +/- 96 on verapamil 240 mg/day, 212.5 +/- 129.3 on verapamil 360 mg/day (p less than 0.001). While taking verapamil in 9 patients 240 mg/day the test was interrupted with of ECG alterations; at the same work load, only 1 patient had ECG alterations while taking verapamil 360 mg/day (p less than 0.01) and 9 completed the test without ECG alterations. The pressure-rate product at maximum exercise was not significantly affected by treatments. The higher dosage of verapamil prolonged the P-R interval (p less than 0.01) but only 1 patient had first-degree AV block. It is concluded that verapamil is a powerful and safe drug in the treatment of effort-induced angina: there is evidence that the effect depends on the dosage administered.
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Besides the anatomoclinical correlates of disturbances in impulse formation and conduction, this article also considers the three mechanisms now known to underlie tachyarrhythmias: focally enhanced automaticity, triggered activity, and, in particular, reentry.
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Sulfobromophthalein dye test and galactose tolerance test were performed, using both substances simultaneous i.v. injection, in 48 subjects with chronic persistent hepatitis, chronic active hepatitis and liver cirrhosis (with and without ascites). As control group 10 normal subjects were tested. Sulfobromophthalein excretion constant ( K1BSF ) drawn from the first part of the retention curve, and the galactose excretion constant (K Gal) were considered. The following conclusions were obtained: a) K1 BSF and K Gal are well-correlated; b) K1 BSF appears more sensitive for a whole evaluation of liver involvement, in absence of evident jaundice (total serum bilirubin less than 6 mg/100 ml); c) K Gal is less reliable in presence of ascites because of the artificial increase in galactose plasmatic clearance provoked by the substance passage to the effusion fluid; d) the statistical analysis using discrimining function methods makes possible a better distinction among the various kinds of liver diseases; e) the same type of statistical analysis shows a difference between cirrhotics with ascites responding to medical therapy in comparison to treatment- resistent ascites. This fact may account for a different level of hepatic functional activity.
Studies conducted by others have revealed that 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), a proximal metabolite of dichlorodiphenyltrichloroethane (DDT), is a strong hepatocellular carcinogen in mice. Since hamsters appear to be resistant to tumor induction by DDT, we wanted to investigate whether DDE has any neoplastic effect in this species. DDE (99% pure) was mixed into the diet at doses of 500 or 1000 ppm and given to groups of male and female Syrian golden hamsters for life. Another group of animals received a diet containing 1000 ppm technical-grade DDT, and a further group served as control. Groups contained a minimum of 40 hamsters per sex. The tested compounds had no effect on the incidence of tumors at all sites, compared to controls. A specific finding in animals exposed to DDE was the appearance of hepatocellular tumors late in life. They were classified as neoplastic nodules, and the incidence was 15% in females and 47% in males of the 500-ppm DDE dose groups and 21% in females and 33% in males of the 1000-ppm DDE dose groups. None of the untreated or DDT-treated animals had these tumors. Eight animals treated with 1000 ppm DDE and four of those treated with DDT had hyperplastic foci of the liver. In addition, adrenocortical adenomas, spontaneous to Syrian golden hamsters, were more frequent in DDE- and DDT-treated animals than in control animals. These results showing that DDE, but not its parental compound, induces liver cell tumors in hamsters emphasize the importance of this metabolite as a proximal carcinogen of DDT.