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Biomedical subjects

G Gatti

Publications and source records attributed to G Gatti.

At least 163 records · Page 9Linked to original sources
PubMed1985

[Viral hepatitis. Epidemiologic evaluation of a personal case load in the area of Casale Monferrato in the years 1981-1982].

The results are reported of an epidemiological assessment of 94 patients hospitalised with diagnosed acute viral hepatitis in the Infectious Disease Division of the S. Spirito Hospital, Casale Monferrato in the period march 1 1981, april 30 1982. Hepatitis was found to occur most frequently among young (under 30) males. There were more positive than negative HBsAg cases, most of the latter arising in heroin addicts.

Adult↗
PubMed1985

Crystal structure of ferric Aplysia limacina myoglobin at 2 X 0 A resolution.

The three-dimensional structure of ferric myoglobin from the mollusc Aplysia limacina has been refined at 2 X 0 A resolution. The crystallographic R factor, calculated at this stage, is 0 X 194. Despite its high content of apolar residues (both aromatic and aliphatic), Aplysia limacina myoglobin, which contains only one histidine residue (at the proximal position), has a structure that conforms to the common eight-helices globin fold observed in other phyla.

Amino Acid Sequence↗
PubMed1985

Mono- and bidimensional 500 MHz 1H-NMR spectra of a synthetic pentasaccharide corresponding to the binding sequence of heparin to antithrombin-III: evidence for conformational peculiarity of the sulfated iduronate residue.

1H-NMR spectra of the synthetic pentasaccharide (N-sulfate-6-0-sulfate-alpha-D-glucosamine) 1----4 (beta-D-glucuronic acid) 1----4 (N-sulfate-3,6-di-0-sulfate-alpha-D-glucosamine) 1----4 (2-0-sulfate-alpha-L-iduronic acid) 1----4 (N-sulfate-6-0-sulfate-alpha-D-glucosamine), corresponding to the active site of heparin for antithrombin (AT-III), have been resolved at 500 MHz and assigned by mono- and bidimensional techniques. Vicinal proton coupling constants of the D-glucosamine residues are similar to those in the regular sequences of heparin, indicating that the 4C1 conformation of the ring, and preference for the g,g conformation of the sulfated hydroxymethyl groups of these residues are neither affected by the unique 3-0-sulfo group nor by sequence effects. By contrast, an unusually large coupling between H-2 and H-3 of the sulfated L-iduronic acid residue suggests a greater departure from the 1C4 conformation of this residue. when present in the binding sequence to AT-III than in the regular sequences. Such a departure, leading to different orientation and spacing of essential sulfate groups, may have implications for high-affinity binding to AT-III.

Antithrombin III↗
PubMed1985

Plasma testosterone, estradiol, progesterone and 17-hydroxy-progesterone responses to single-dose stimulation with human chorionic gonadotropin in chronic male alcoholics.

Ten chronic male alcoholics presenting with hypogonadism but without overt liver failure were examined under basal conditions and after stimulation of the testicular steroidogenesis with a single dose of human chorionic gonadotropin (hCG, 2,000 IU im). Plasma concentrations of testosterone (T), 17 beta-estradiol (E2), progesterone (P) and 17-OH progesterone (17-OHP) were measured between 08:00-09:00 prior to injection and then every 24 h at the same time in the morning until the 96th hour following the injection. Controls were 10 male adult volunteers, examined under the same conditions. Four alcoholics underwent a second hCG stimulation after 10 day controlled abstinence from alcohol. Basal plasma T and P were significantly decreased and increased respectively in the alcoholics (p less than 0.001) whereas E2 and 17-OHP were much the same in both groups. The magnitude of the T response to hCG injection was significantly lower in the alcoholics at any considered time (p less than 0.001). The E2 response, too, was lower, whereas the ratio E2 change/T change after hCG was higher. The response peak occurred earlier for E2 than for T both in controls and alcoholics. The mean percent change at 24 h and the mean maximum increase of 17-OHP were higher in the alcoholics (p less than 0.01 and p less than 0.05 respectively). An increase in P after hCG was observed in only 5 alcoholics (responders), while some subjects displayed paradoxical decreases. Abstinence was always followed by an increased T response and a decreased 17-OHP response. The E2 response was unchanged and two P responders displayed an increased response.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗
PubMed1985

Effect of chronic anticonvulsant monotherapy on lymphocyte subpopulations in adult epileptic patients.

Sixty-five patients undergoing long-term monotherapy for at least 3 months with phenytoin, carbamazepine or phenobarbital were screened for lymphocyte and immunoglobulin abnormalities. In 57% of patients the duration of therapy was longer than 12 months. The control subjects were matched for sex and age and none of them was taking drugs. The average serum immunoglobulin (IgG, IgA, IgM) values did not differ in control and patient groups. A significant decrease of OKT4+ cells was seen with all drugs, while other lymphocyte subpopulations were differently affected depending on the drug used. It is concluded that long-term single-drug treatment with phenytoin, carbamazepine and phenobarbital exhibits immunosuppressant effects through a complex action which involves more than one lymphocyte subpopulation. Moreover, the possible interference of the disease state with the immune functions of epileptic patients is discussed.

Adolescent↗
PubMed1984

Crystallization of hen egg-white avidin in a tetragonal form.

Hen egg-white avidin has been crystallized at pH 5.7 from ammonium sulfate solutions. The crystals belong to the tetragonal space group P4(2)2(1)2, with unit cell edges a = b = 79.6 A, c = 84.3 A. Assuming a molecular weight of 15,600 per avidin monomer, this crystal form is compatible with the presence of a dimer in the asymmetric unit, and is suitable for a crystallographic structural investigation at high resolution.

Animals↗
PubMed1984

Ca2+-dependent and -independent release of neurotransmitters from PC12 cells: a role for protein kinase C activation?

The intracellular mechanisms regulating the process of evoked neurotransmitter release were studied in the cloned neurosecretory cell line PC12. Various agents were employed that were known, from previous studies in other systems, to stimulate release in a manner either strictly dependent or independent of the concentration of extracellular Ca2+, [Ca2+]o. Three parameters were investigated in cells suspended in either Ca2+-containing or Ca2+-free Krebs-Ringer media: release of previously accumulated [3H]dopamine; average free cytoplasmic Ca2+ concentration, [Ca2+]i (measured by the quin2 technique); and cell ultrastructure, with special reference to the number and structure of secretion granules. The release induced by the ionophores transporting monovalent cations, X537A and monensin, occurred concomitantly with profound alterations of secretory granule structure (swelling and dissolution of the dense core). These results suggest that the effect of these drugs is due primarily to leakage of dopamine from granules to the cytoplasm and extracellular space. In contrast, the changes induced by other stimulatory drugs used concerned not the structure but the number of secretory granules, indicating that with these drugs stimulation of exocytosis is the phenomenon underlying the increased transmitter release. The release response induced by the Ca2+-ionophore ionomycin was dependent on [Ca2+]o, occurred rapidly, was concomitant with a marked rise of [Ca2+]i, and ceased after 1-2 min even though [Ca2+]i remained elevated for many minutes. 12-O-tetradecanoylphorbol, 13-acetate and diacylglycerol (both of which are known as activators of protein kinase C) induced slow responses almost completely independent of [Ca2+]o and not accompanied by changes of [Ca2+]i. Combination of an activator of protein kinase C with a low concentration of ionomycin failed to modify the [Ca2+]i rise induced by the ionophore, but elicited a marked potentiation of the release response, which was two- to fourfold larger than the sum of the responses elicited separately by either drugs. Thus, activation of protein kinase C seems to play an important role in the regulation of exocytosis in neurosecretory cells, possibly by increasing and maintaining the sensitivity to Ca2+ of the intracellular apparatus regulating granule discharge by exocytosis.

Adrenal Gland Neoplasms↗
PubMed1984

Pharmacokinetics of prednisone and its metabolite prednisolone in children with nephrotic syndrome during the active phase and in remission.

The kinetics at steady state of prednisone and its metabolite prednisolone were determined in nine nephrotic children during the active phase of the disease and in remission. There were no differences in serum prednisone levels between the two occasions. Prednisone levels were lower than prednisolone levels. Total serum prednisolone levels were significantly lower during the active phase than in remission (AUC: 2452 +/- 207 vs 3392 +/- 293 ng ml-1 h respectively). Half-life values were similar on both occasions. The binding of prednisolone to serum proteins was markedly impaired during the active phase as compared to the remission. Free fraction values correlated positively with total drug concentration. A negative correlation between free fraction and serum albumin level was found during the active phase. Free prednisolone levels during the active phase did not differ significantly from those observed during remission (AUC: 937 +/- 128 vs 847 +/- 81 ng ml-1 h respectively). These data indicate that pharmacokinetic changes are unlikely to be responsible for alterations in steroid responsiveness in nephrotic patients with hypoalbuminaemia.

Adolescent↗
PubMed1984

Pharmacokinetics of valproic acid in the elderly.

The kinetics of a single oral dose of sodium valproate was studied in six healthy elderly patients (age 68-89 years) and six young control subjects (age 24-26 years). The profiles of total plasma valproic acid (VPA) concentrations were very similar in the elderly and in the young. Half-lives (15.3 +/- 0.7 s.e. mean in the elderly vs 13.0 +/- 1.0 h in the young), volumes of distribution (0.16 +/- 0.01 l/kg in the elderly vs 0.14 +/- 0.01 l/kg in the young) and clearance (7.5 +/- 0.9 ml h-1 kg-1 in the elderly vs 7.7 +/- 0.6 ml h-1 kg-1 in the young) did not differ significantly between the two groups. Free VPA concentrations were significantly increased in the elderly. The clearance of the free drug (intrinsic clearance) was reduced from 127.0 +/- 12 ml h-1 kg-1 (control value in the young) to 77.7 +/- 5.5 ml h-1 kg-1 (P less than 0.02). Free VPA fraction was 9.5 +/- 0.6% in the elderly and 6.6 +/- 0.5% in the young (P less than 0.02). These findings suggest that the pharmacokinetic alterations of VPA in old age are complex and include at least two separate mechanisms: a decrease in plasma protein binding and a reduction of drug metabolizing capacity resulting in decreased clearance of free drug by the liver.

Adult↗
PubMed1984

Pharmacokinetic and pharmacodynamic studies with a new controlled-release formulation of propranolol in normal volunteers: a comparison with other commercially available formulations.

The kinetics and dynamics (inhibition of exercise tachycardia) of two controlled-release preparations of propranolol (Elanolol and Inderal LA) were examined in six normal volunteers. Conventional propranolol (Inderal) was also studied for comparison purposes. As compared to conventional propranolol (120 mg), single doses of Elanol (120 mg) and Inderal LA (160 mg) produced a smoother serum level profile, with lower and delayed peak times. Dose-corrected AUC0-24 values were greater after Elanol than after Inderal LA (651 +/- 147 vs 402 +/- 159 ng ml-1 h, means +/- s.e. mean, P greater than 0.05). The profile of inhibition of exercise tachycardia mirrored closely that of the serum levels. At steady state, all regimens studied (Inderal 40 mg three times daily; Elanol 120 mg once daily; Inderal LA 160 mg once daily) ensured relatively sustained serum levels and a stable degree of pharmacological effect. Dose-corrected AUC0-24 values were 797 +/- 148 ng ml-1 h after Inderal, 908 +/- 113 ng ml-1 h after Elanol and 602 +/- 122 ng ml-1 after Inderal LA. The bioavailability of Inderal LA was significantly lower than that of the other preparations. These results demonstrate that long-acting formulations of propranolol can be developed which are not necessarily associated with reduced bioavailability secondary to enhanced first-pass metabolism.

Adult↗
PubMed1984

ACTH-producing hypophyseal carcinoma monitored by computed tomography.

A case of malignant ACTH-producing hypophyseal tumor with serial CT scan and histological investigation is discussed. The neoplasm became evident with a Cushing's syndrome and was treated with adrenalectomy and radiotherapy. Nelson's syndrome subsequently developed due to histologically atypical adenoma. Subarachnoid metastases occurred after 4 years, finally causing a fatal intracranial hemorrhage.

Adenocarcinoma↗
PubMed1984

Malignant evolution of an ACTH-producing pituitary tumor treated with intrasellar implantation of 90Y. Case report and review of the literature.

A case of pituitary carcinoma is here presented, together with a review of the 25 cases so far reported in the literature. After a long-standing history of Cushing's disease, treated with interstitial pituitary irradiation and total adrenalectomy, Nelson's syndrome developed due to a pituitary neoplasm that finally spread through the subarachnoidal space, bringing the patient to death. The possible long-term role of surgery and radiotherapy in switching an aggressive behavior is also discussed.

Adrenalectomy↗
PubMed1984

Alpha latrotoxin of black widow spider venom: an interesting neurotoxin and a tool for investigating the process of neurotransmitter release.

Alpha latrotoxin, purified from the venom of the black widow spider, is a high Mr (130000) protein devoid of detectable enzymatic activity. When applied to vertebrate nerve terminals (of the central as well as peripheral nervous systems) the toxin elicits massive release of neurotransmitters by stimulating the fusion of synaptic vesicles with the presynaptic membrane (exocytosis). Among non-neuronal systems, only the neurosecretory cell line PC12 is sensitive to alpha latrotoxin; all others investigated so far are insensitive. In order to act, alpha latrotoxin requires the presence of divalent cations in the medium. Ca2+ can be substituted by other divalent cations as Sr2+, Ba2+, Mn2+, Mg2+. However, with the last two the catecholamine release response is reduced in PC12 cells and synaptosomes. A specific, high affinity receptor of alpha latrotoxin exists in preparation sensitive to the toxin. This receptor has been purified and found to be a high Mr, integral membrane protein. In the frog neuromuscular junction the receptor is localized exclusively in the presynaptic membrane. Binding of alpha latrotoxin to the receptor in a Ca2+-containing incubation medium induces membrane depolarization (insensitive to tetrodotoxin), stimulation of Ca2+ influx (insensitive to verapamil) with consequent increase in the cytoplasmic free Ca2+ concentration and stimulation of phosphoinositide breakdown. In Ca2+ free medium depolarization is maintained, but free Ca2+ concentration does not rise after toxin application. In conclusion, alpha latrotoxin seems to act through a dual mechanism. The Ca2+-independent part of this mechanism may be mediated by the activation of protein kinase C, triggered by phosphoinositide metabolism. The relevance of these findings for presynaptic physiology is discussed.

Animals↗
PubMed1984

[Computerized tomography of bladder neoplasms].

A comparison was made between the pelvic CT picture and clinical and instrumental findings in 89 patients with bladder neoplasm. A close critical assessment was also made of CT as a reliable way of determining the TNM stage, and its effective aid in the choice of a therapeutic strategy. The advantages and limits of CT are discussed. The conclusion is drawn that it is of assistance in overall TNM rating, and may sometimes provide useful informations concerning the involvement of surrounding structures. Particularly as far as the choice of radical management is concerned, however, it is prone to by no means negligible staging errors, though these are open to correction in the light of non-radiological criteria.

Adult↗
PubMed1983

Structure-activity relationship in heparin: a synthetic pentasaccharide with high affinity for antithrombin III and eliciting high anti-factor Xa activity.

The structures of the tetrasaccharide (beta-D-glucuronic acid)1 leads to 4 (N-sulfate-3,6-di-0-sulfate-alpha-D-glucosamine)1 leads to 4(2-0-sulfate-alpha-L-iduronic acid)1 leads to 4(N-sulfate-6-0-sulfate-D-glucosamine) and of the pentasaccharide (N-sulfate-6-0-sulfate-alpha-D-glucosamine)1 leads to 4(beta-D-glucuronic acid)1 leads to 4(N-sulfate-3,6-di-0-sulfate-alpha-D-glucosamine)1 leads to 4(2-0-sulfate-alpha-L-iduronic acid)1 leads to 4(N-sulfate-6-0-sulfate-D-glucosamine), both prepared for the first time, by chemical synthesis from D-glucose and D-glucosamine, have been confirmed by nuclear magnetic resonance. The synthetic tetrasaccharide neither binds to AT-III nor induces anti-factor Xa activity enhancement of this inhibitor. In contrast, the synthetic pentasaccharide strongly binds to AT-III (Ka: 7.10(6)M-1) forming an equimolar complex and also enhances the AT-III inhibitory activity towards factor Xa. These results confirm that the synthetic pentasaccharide with the above structure corresponds to the actual minimal sequence required in heparin for binding to AT-III.

Antithrombin III↗
PubMed1983

A new crystalline modification of the copper enzyme ascorbate oxidase.

The copper enzyme ascorbate oxidase, purified from green zucchini squash, has been crystallized at pH 5.4 employing the organic solvent 2-methyl-2,4-pentanediol. The crystals obtained are larger than one millimetre and belong to the space group P2(1)2(1)2, with unit cell parameters; a = 106.7 A, b = 105.1 A, c = 113.5 A. The crystallographic asymmetric unit contains two subunits of the enzyme (Mr = 140,000) and the solvent content of the crystals is 46% (v/v). The diffraction pattern extends to 2.5 A resolution; this crystal form is suitable for a X-ray structural investigation.

Ascorbate Oxidase↗
PubMed1983

[Kinetics of erythrocyte populations in newborn infants with hyperbilirubinemia].

Determinations of erythrocyte glucose-6-phosphate dehydrogenase, pyruvate kinase and glucose-phosphate isomerase activities have been carried out in jaundiced and non-jaundiced newborn infants at birth and after 5 days of life. Only hyperbilirubinemias of unknown etiology have been considered. Previous investigations have demonstrated that erythrocyte age dependent enzyme activities decrease in the healthy newborn during the first week of life. Following the results of the present paper, jaundiced newborns do not show such a decrease, since a statistically significant difference between paired data of glucose-6-phosphate dehydrogenase and pyruvate kinase in jaundiced and non-jaundiced newborns have been found. It is likely that the lack of decrease of enzyme activities in the jaundiced infants depend upon the loss of oldest red cells with low glucose-6-phosphate dehydrogenase and pyruvate kinase. Our observation suggests the occurrence of a slight hemolysis in newborn infants with hyperbilirubinemia of unknown etiology.

Erythrocyte Aging↗