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Biomedical subjects

A Ricci

Publications and source records attributed to A Ricci.

At least 19 recordsLinked to original sources
PubMed1995

Analysis of protein-protein interactions involved in the activation of the Shc/Grb-2 pathway by the ErbB-2 kinase.

In murine fibroblasts activation of the Shc/Grb-2 pathway by the ErbB-2 kinase involves tyrosine phosphorylation of Shc products and the formation of Shc/ErbB-2, Shc/Grb-2 and Grb-2/ErbB-2 complexes. Tyr 1139 of ErbB-2 bound to the Grb-2 SH2 domain in vitro as well as in intact cells. Tyr 1221 and 1248 are binding sites of gp185ErbB-2 for Shc SH2 domain in vitro whereas Tyr 1196 and 1248 are major binding sites of ErbB-2 for Shc PTB domain. Inhibition of Shc/ErbB-2 complex formation in intact cells was obtained by simultaneous mutational inactivation of Shc SH2 and Shc PTB binding sites of gp185ErbB-2. Shc/ErbB-2 complexes are formed upon activation of the ErbB-2 kinase and tyrosine phosphorylation of Shc proteins; they are located in both cytosol and cellular membranes. ErbB-2 activation induces also translocation of Grb-2 from cytosol to membranes. This network of protein-protein interactions may reflect the ability of the Shc/Grb-2 pathway to act as a molecular switch controlling different cellular functions regulated by RTK activation. In fact the Ras GDP exchanger mSOS was recruited in Grb-2/ErbB-2 complexes; furthermore besides mSOS, other polypeptides present in either cytosolic or membrane preparations were able to complex in vitro with Grb-2 SH3 domains.

3T3 Cells↗
PubMed1994

Influence of long-term treatment with L-deprenyl on the age-dependent changes in rat brain microanatomy.

The present study was designed to assess whether treatment with the monoamine oxidase-B (MAO-B) inhibitor L-deprenyl, which has been documented to increase both mean and maximum survival in aged rats as well as sexual performance and cognitive function, has any effect on the age-related microanatomical changes occurring in the rat brain. Male Sprague-Dawley rats received a subcutaneous injection of 0.25 mg/kg L-deprenyl every other day from the 19th to the 24th month of age. Age-matched control rats were injected with saline, whereas 11-month-old untreated rats were used as an adult reference group. Both body and brain weight were increased as a function of age, and they were unaffected by treatment with L-deprenyl. The density of nerve cell profiles in the frontal cortex, in the CA-1 and CA-3 subfields of the hippocampus, in the dentate gyrus and in the cerebellar cortex were decreased in aged rats in comparison with adult rats. The density of nerve cell profiles in the above brain areas of L-deprenyl-treated rats was not significantly higher in comparison with age-matched control animals with the exception of Purkinje neuron profiles. The intensity of Nissl's staining, which may be related to the protein synthetic capabilities of nerve cells, is reduced within pyramidal neurons of the hippocampus and Purkinje neurons of the cerebellar cortex of aged rats. The intensity of Nissl's staining in L-deprenyl-treated rats was not different from adult rats. Lipofuscin deposition was significantly increased within the cytoplasm of pyramidal neurons of the frontal cortex, of the CA-3 subfield of the hippocampus and of Purkinje neurons of the cerebellar cortex. L-Deprenyl administration decreased lipofuscin accumulation within the cytoplasm of the above mentioned nerve cell types. The density of sulphide-silver staining in the intrahippocampal pathway of mossy fibres, which participate in the elaboration of passive avoidance responses, is decreased in aged rats. Treatment with L-deprenyl counters this age-related reduction. The above results suggest that long-term treatment with L-deprenyl is able to counter the expression of some microanatomical changes typical of aging brain.

Aging↗
PubMed1992

[The prevention of venous thromboembolism in Italy].

A questionnaire concerning the prophylaxis of venous thromboembolism was filled in by 326 surgical departments in Italy. In 58% the prophylaxis was routinely used and in 29% more than one method was used. The most used method of prevention was subcutaneous heparin followed by elastic compression. In 51% of the centers the prophylaxis was used only in high risk patients and in 22% it was not used at all. The most relevant risk factors in the development of thrombosis were considered age, tumors and obesity. Finally in a questionnaire sent to 350 vascular laboratories it was found that--according to the operators--76% of all documented thromboses were possibly consequent to surgical procedures (in 86% no prophylaxis had been used).

Bandages↗
PubMed1992

Pericardial agenesis and focal aplasia cutis in tetrasomy 12p (Pallister-Killian syndrome).

We report a stillborn female infant with multiple internal and external anatomic abnormalities and mosaicism for isochromosome 12p. These abnormalities included webbed neck, low-set ears, lower jaw tooth bud, left simian crease, shield chest, focal aplasia cutis, diaphragmatic hernia, hypoplastic lungs, agenesis of pericardium, and Meckel's diverticulum. Karyotypic analysis on cord blood lymphocytes showed 10% mosaicism of 46,XX/47,XX, + i(12p), and analysis of skin fibroblasts showed 50% mosaicism for the same karyotype. The parental karyotypes were normal. There are many reported cases describing the anomalies seen in isochromosome 12p. None of these cases, however, have displayed pericardial agenesis or aplasia cutis. The clinical and cytogenetic features of Pallister-Killian syndrome are reviewed.

Abnormalities, Multiple↗
PubMed1992

Localization of 5-hydroxytryptamine-like immunoreactive cells and nerve fibers in the rat female reproductive system.

The presence of 5-hydroxytryptamine (5-HT)-like immunoreactivity (IR) was studied in the rat female reproductive system using polyclonal antibodies directed against 5-HT. Moreover, 5-HT levels in the ovary, oviduct, uterus, and cervix were measured by high-pressure liquid chromatography with electrochemical detection. The highest 5-HT concentrations were found in the oviduct, followed in descending order by the cervix, the ovary, and the uterus. Most 5-HT-like IR was observed in the cytoplasm of mast cells. These cells were found in the connective tissue around the fimbria, in the oviduct, in the uterus, and in the ovary. Mast cells are clustered in the proximity of the parenchymal blood vessels. Moreover, a few 5-HT-like nerve fibers were found distributed mainly perivascularily in the uterine cervix and in the uterine horns as well as in the oviduct. IR nerve fibers were rarely seen within the ovary. The present data provide direct evidence that 5-HT in the female reproductive system not only is associated with mast cells but is located in nerve fibre-like structures as well. The functional significance of this probable 5-HT-ergic innervation of the female reproductive tract discovered in the present study should be clarified in future investigations.

Animals↗
PubMed1992

Direct demonstration of dopamine D1-like receptor sites in the ciliary body of the rabbit eye by light microscope autoradiography.

The pharmacological characteristics and the anatomical localization of [3H]-SCH 23390 in sections of the ciliary body of the rabbit eye were analyzed using a radioreceptor assay and autoradiographic techniques. [3H]-SCH 23390 was bound to sections of rabbit ciliary body in a manner consistent with the labelling of D1-like receptor sites. The dissociation constant (Kd) was 0.62 nmol/l, while the maximum binding capacity (Bmax) was 117 +/- 9 fmol/mg tissue. Light microscope autoradiography revealed [3H]-SCH 23390 binding sites within the epithelium of the ciliary processes, which is the ocular structure involved in the secretion of aqueous humor. No specific accumulation of silver grains was noticeable within the iridocorneal angle, which is the structure involved in the outflow of aqueous humor. These findings suggest that the rise in intraocular pressure caused by D1 receptor agonists is probably mediated by an increase of aqueous humor formation rather than by an inhibition of the outflow of aqueous humor.

Animals↗
PubMed1992

Oral choline alfoscerate counteracts age-dependent loss of mossy fibres in the rat hippocampus.

Mossy fibres represent a major intrahippocampal associative pathway. They consist of axons of granule cells of the dentate gyrus and show an age-dependent loss as do the granule cells of the dentate gyrus. The present study was designed to assess whether long-term treatment of rats with choline alfoscerate in their drinking water would be effective in countering the loss of mossy fibres and of granule cells occurring with aging. Choline alfoscerate is a precursor in the biosynthesis of brain phospholipids and increases the bioavailability of choline in nervous tissue. Male Sprague-Dawley rats of 18 months of age were divided into two groups. One group received a daily dose of 100 mg/kg choline alfoscerate for 6 months; the other group was used as an untreated control. Twelve-month-old untreated animals were used as a reference group. The area occupied by mossy fibres, as well as their density, was significantly reduced in 24-month-old control rats in comparison with 12-month-old rats. The same is true for the density granule cells of the dentate gyrus which was decreased by about 20% in the oldest animals. In choline alfoscerate-treated rats both the area occupied by mossy fibres and their density were significantly higher than in age-matched controls. Moreover, the number of granule neurons of the hippocampus was higher by about 7% in choline alfoscerate-treated than in control 24-month-old rats. The above data suggest that choline alfoscerate treatment counteracts some anatomical changes of the rat hippocampus occurring in old age.

Administration, Oral↗
PubMed1992

Propionyl-L-carnitine: a new compound in the metabolic approach to the treatment of effort angina.

The effects of propionyl-L-carnitine on exercise tolerance of 12 patients with stable exertional angina were assessed in a double-blind, placebo-controlled, cross-over protocol using serial exercise tests. Compared to placebo, propionyl-L-carnitine significantly increased total work from 514 +/- 199 to 600 +/- 209 W (P less than 0.05) (17%) and prolonged exercise time and time to ischemic threshold from 515 +/- 115 to 565 +/- 109 sec (P less than 0.05) (10%) and from 375 +/- 102 to 427 +/- 93 sec (P less than 0.01) (14%), respectively. ST segment depression at the highest common work level was significantly reduced from 0.19 +/- 0.08 to 0.15 +/- 0.08 mV (P less than 0.05) (21%). No significant changes in heart rate, systolic blood pressure, and rate-pressure product at rest, at the highest common work level, on appearance of the ischemic threshold, or at peak exercise were observed after propionyl-L-carnitine treatment. No side effects were observed under propionyl-L-carnitine treatment. This study shows that propionyl-L-carnitine can significantly improve exercise tolerance in patients with stable angina. Our data seem to confirm that propionyl-L-carnitine most likely exerts its protective action via the metabolic pathway.

Adult↗
PubMed1992

Adenoid cystic carcinoma of Cowper's gland.

We report an additional case of primary adenoid cystic carcinoma of Cowper's gland in an otherwise healthy asymptomatic 66-year-old man. Based on a review of similar lesions presenting in the head and neck, our treatment plan entailed pelvic exenteration followed by radiation therapy. Whether adenoid cystic carcinoma of Cowper's gland behaves as aggressively as it does in the head and neck remains unclear. However, in view of the extensive local invasion in our patient and a previously successful outcome, a combined surgical and radiation approach appears to be the most appropriate therapy.

Aged↗
PubMed1992

Dopexamine hydrochloride in the human heart: receptor binding and effects on cAMP generation.

Dopexamine hydrochloride is a synthetic catecholamine proposed for the short-term treatment of heart failure and postoperative low cardiac output. The pharmacological profile and anatomical localization of dopexamine binding were investigated in sections of right and left ventricle using [3H]-dopexamine and ligand techniques associated with light microscope autoradiography. Its effects on the 3-5-cyclic adenosine monophosphate (cAMP) generating system in membrane particles of the human right or left ventricle were also studied. [3H]-Dopexamine was specifically bound to sections of human right or left ventricle. The binding was time-, temperature- and concentration-dependent and was dissociable. The apparent equilibrium constant of dissociation was 3.5 nM. A decreased [3H]-dopexamine binding capacity from the base to the apex and ventricles was noticeable. The pharmacological profile of [3H]-dopexamine binding to sections of right or left ventricle was consistent with the labelling of both beta 2-adrenoceptors and dopamine DA-2 receptors. The most potent displacer of [3H]-dopexamine was the beta 2-adrenoceptor antagonist ICI 118,551 followed by dopamine, noradrenaline and domperidone. The beta 1-adrenoceptor antagonist metoprolol or the dopamine DA-1 receptor antagonist SCH 23390 were ineffective as displacers of [3H]-dopexamine binding. Light microscope autoradiography revealed the localization of [3H]-dopexamine binding sites within the wall of the human right and left ventricle. The density of silver grains was slightly higher in the right than in the left ventricle and showed a uniform transmural distribution across the ventricular wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Fibrinolytic enhancement in diabetic microangiopathy with defibrotide.

Skin microcirculation was evaluated in 117 patients with diabetic microangiopathy over a period of six months. They were divided into two groups. Group 1 (64 patients) was treated with oral defibrotide, a new profibrinolytic drug, in association with diet and oral antidiabetic drugs. Group 2 (53 patients) was treated only with diet and antidiabetic agents. The microcirculation was studied by means of laser-Doppler flowmetry transcutaneous partial pressure of oxygen and carbon dioxide pressure measurements, and evaluation of capillary filtration. After six months, patients in group 1 improved their microcirculatory parameters in association with an improvement in signs and symptoms. Moreover, 30 patients in group 1 and 36 in group 2 were followed up for eighteen months, and the authors observed that the deterioration of the microcirculatory parameters was significantly slowed in diabetics treated with defibrotide. A decrease in plasma fibrinogen during defibrotide treatment was observed in all treated patients in association with an increased fibrinolytic activity. In conclusion, it appears that defibrotide, enhancing fibrinolysis, improved the microcirculation in diabetics, preventing further, progressive deterioration.

Adult↗
PubMed1992

Pharmacological characterization and autoradiographic localization of dopamine receptors in human epicardial arteries.

The pharmacological properties and the anatomical localization of dopamine (DA) D1 and D2 receptor sites were studied in normal samples of the human right coronary and anterior interventricular arteries by assessing the effect of DA on the cyclic AMP generating system and by using combined radioreceptor binding and autoradiographic techniques. DA caused a concentration-dependent accumulation of cyclic AMP in membranes of right and anterior interventricular coronary arteries. This effect was antagonized by the selective D1 receptor antagonist SCH 23390 and by other DA receptor antagonists. D2 receptor responses negatively coupled to cyclic AMP generation were obtained by incubating membranes of coronary arteries with DA together with SCH 23390 or with D2 receptor agonists. This D2 effect was abolished by the selective D2 receptor antagonist (-)-sulpiride. [3H]SCH 23390 was bound to sections of the coronary arteries in a manner consistent with the labeling of D1 sites. Light microscope autoradiography revealed the localization of D1 sites in the medial layer of the coronary arteries. [3H]Spiroperidol, in the presence of ketanserin, was bound to sections of the coronary arteries in a manner consistent with the labeling of D2 sites. D2 receptor sites were located within the adventitia and the adventitial-medial border of the two arteries, and are probably prejunctional in nature. These findings indicate the existence of both D1 and D2 receptor sites in human right and anterior interventricular arteries. Moreover, they suggest that coronary vasodilation induced by DA or DA receptor agonists may be the result of a direct coronary vasodilatory activity.

Adolescent↗
PubMed1992

Detection of occult metastatic lobular carcinoma in axillary lymph nodes using anticytokeratin monoclonal antibodies.

To examine the importance of immunocytochemically detectable occult axillary lymph node metastases in patients with lobular carcinoma of breast, tumor registry data from 54 cases indexed as lobular carcinoma during the period 1973-82 were reviewed. Recurrences and/or deaths due to cancer were essentially confined to the group of patients with a component of invasive lobular carcinoma (ILC), therefore this subset was selected for further study. Seven of 20 cases had lymph node metastases diagnosed histologically at the time of mastectomy. Follow-up of these patients showed four dead of disease (DOD) at one, three, three, and seven years; one alive with disease (AWD) at one year; and two with no evidence of disease (NED) at four and five years. Eleven of 20 were node negative. Follow-up of this group showed nine NED and two DOD at two and four years. Two of 20 had unknown node status. Formalin-fixed, paraffin embedded lymph node blocks were available in 12 of 20 cases with a component of ILC. Of these, 4/12 cases had histologically positive nodes while 8/12 were originally diagnosed as negative. A cytokeratin monoclonal antibody cocktail (MAK-6, CAM 5.2 and AE1/AE3) was applied to all 12 cases. Cytokeratin immunoreactivity (CK-IR) was found in all four cases that were histologically positive. Five of eight histologically negative nodes lacked CK-IR, however the other three cases showed CK-IR in micrometastases. Review of newly prepared hematoxylin-eosin sections from the paraffin blocks failed to demonstrate metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Deficits in cholinergic neurotransmission markers induced by ethylcholine mustard aziridinium (AF64A) in the rat hippocampus: sensitivity to treatment with the monoamine oxidase-B inhibitor L-deprenyl.

Assessment was made of the effects of intracerebroventricular (i.c.v.) administration of ethylcholine mustard aziridinium (AF64A) and of the monoamine oxidase (MAO)-B inhibitor L-deprenyl on the acetylcholine (ACh) biosynthetic enzyme choline acetyltransferase (ChAT), on the ACh catabolic enzyme acetylcholinesterase (AChE) and on the density of ACh muscarinic M-1 and M-2 receptor sites. In addition, the effect of AF64A and of L-deprenyl treatment on the localization of AChE activity in the CA-1 and CA-3 fields of the hippocampus was evaluated by combined enzyme histochemistry and microdensitometry techniques. I.c.v. injection of AF64A induced, 4 weeks after administration of the neurotoxin, a remarkable increase of MAO-B activity, and a significant reduction of ChAT and AChE activities in the hippocampus but not in the neostriatum which was used as a reference tissue. Hippocampal muscarinic M-1 receptors were unaffected by AF64A administration, whereas M-2 sites were reduced after neurotoxin injection. Enzyme histochemistry analysis showed that the loss of AChE induced by AF64A was more pronounced in the CA-3 than in the CA-1 field of the hippocampus. Treatment with L-deprenyl induced, from a dose of 11.17 microM/kg/day, a significant reduction of MAO-B activity in the hippocampus. The expression of ChAT and AChE, as well as the density of M-2 receptors, was increased after L-deprenyl administration in the hippocampus but not in the neostriatum. An increase in AChE reactivity was noticeable in the CA-1 and CA-3 fields of the hippocampus of AF64A-injected rats treated with L-deprenyl.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗
PubMed1992

Endothelial dopamine DA-1 receptor sites in the rabbit pulmonary artery: autoradiographic demonstration.

Combined in vivo radioreceptor binding and autoradiographic techniques were used to characterized the pharmacological profile and to study the anatomical localization of dopamine (DA) DA-1 receptor sites in sections of rabbit pulmonary artery. [3H]R-(+)-8-chloro-2,3,4,5-tetrahydro-5-phenyl-1H-3-benzazepin-7- alhemimaleate (SCH 23390), which was used as a ligand, was bound by sections of rabbit pulmonary artery in a manner consistent with the binding of DA DA-1 sites. The Kd value was 4.75 nM, whereas the Bmax value was 78.3 +/- 5.7 fmol/mg tissue. Light microscope autoradiography demonstrated specific [3H]SCH 23390 binding sites primarily in the endothelium of the rabbit pulmonary artery. Moreover, sparse receptor sites were visualized in the medial layer. Mechanical removal of endothelium caused the disappearance of [3H]SCH 23390 binding sites showing the endothelial localization, but was without effect on the receptor sites of the medial layer. The present findings suggest that differently from systemic arteries, where DA-1 receptor sites are localized in the medial layer, probably within smooth muscle, the majority of DA-1 sites in the rabbit pulmonary artery are endothelial. The possible significance of these sites visualized in the present study for the first time is discussed.

Animals↗
PubMed1992

Acute effects of hydroxyethylrutosides on capillary filtration in normal volunteers, patients with venous hypertension and in patients with diabetic microangiopathy (a dose comparison study).

The acute effects of hydroxyethylrutosides on capillary filtration were studied in 12 normal subjects, 25 patients with venous hypertension and 22 diabetics with microangiopathy. The two groups of patients randomly received a single oral dose (500 or 1000 mg) of hydroxyethylrutosides. A single dose of 500 mg was used for normal volunteers. In the following 6 hours capillary filtration was studied with straingauge plethysmography. The decrease in capillary filtration was evident within the first hour and was at its peak between the second and fourth hour. After 6 hours it was still significantly below baseline values in patients. The 1000 mg dose was significantly more effective in both groups of patients. This study confirms the efficacy of hydroxyethylrutosides in decreasing capillary filtration. It suggests that the effect of one dose lasts at least 6 hours and also that the higher dose is more effective.

Adult↗