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Biomedical subjects

A Ambrosini

Publications and source records attributed to A Ambrosini.

At least 73 records · Page 4Linked to original sources

Gestational trophoblastic disease in the Gynaecologic and Obstetric Institute of Sassari in the period 1976-89.

61 cases of gestational trophoblastic disease (GTD) were examined retrospectively in the period 1976-89 (60 cases of simple vesicular mole and one case of chorionepithelioma), analysing them from the epidemiologic point of view. The incidence of GTD were 3.6/1000 live births, higher than the Italian and European average, with a very low incidence, on the contrary, of chorionepithelioma (0.06/1000 live births). No significant epidemiological data emerged, with the exception of age (11 cases of over 40 years) and of ABO typing (a notable incidence of ORh + group). The gestational capacity of the patients returning for checking was 78.9%, similar to that of the general population.

Adult↗

Fist line chemotherapy in advanced ovarian cancer: a comparison of three therapeutic regimes.

The first line polichemotherapeutic regimens are compared (intracavitary Cyclophosphamide + CMF, ACy and PEC) in 47 patients with advanced ovarian carcinoma. The response was 56.4% for Ex-CMF (CR 39.1%), 76.8% for ACy (CR 61.5%) and 81.8% for PEC (CR 63.6%). The three-year survival was 39.1% with Ex-CMF, 53.8% with ACy and 72.7% (follow-up not yet completed) for PEC. Toxicity was modest in all the three therapeutic regimens.

Adult↗

Endometrial carcinoma in the Sardinian population.

The biological and clinical characteristics of endometrial carcinoma in Sardinia were examined, with particular regard to the very high incidence (42.7/100,000 age-selected women) of this neoplasia in this Island. The use of post-surgical Radiotherapy on the basis of the protocols of integrated therapies allowed us to reduce the incidence of relapses in these last few years, with an evident increase in survival.

Adult↗

Endocavitary beta-interferon in neoplastic effusions.

Thirteen patients with malignant genital or mammary neoplasias, with endocavitary neoplastic effusion (pleural or ascitic), were examined in order to study the modifications of neoplastic effusion in endocavitary treatment (intrapleural or intraperitoneal) with Beta-Interferon. There was an overall objective response in 70% of the patients treated, with 53.8% complete responses and an average duration response of above 6 months. The best results were obtained in patients with ovarian cancer, with 75% of objective responses (50% CR), confirming the efficacy of Beta-Interferon particularly at peritoneal level, where there is higher concentration and exposure of the drug in the site of disease.

Adult↗

The modifications of T-lymphocyte cell subpopulations in patients with beta-interferon intracavitary treatment.

18 patients with malignant genital or mammary neoplasia, treated with endocavitary Beta-Interferon (intrapleural or intraperitoneal), were examined in order to study the modifications of T-lymphocyte subpopulations (T3, T4, T8, T4/T8) in the peripheric blood. An improvement in the immune state in complessively 50% of the patients treated was observed, while there were no modifications in the remaining patients (in 3 patients with advanced ovarian cancer there was persistence of immunodepression preexisting to treatment). This indicates that endocavitary Beta-Interferon induced very poor immune response at peripheric level (contrary to what other Authors have described at peritoneal level), correlated to the dose used and to the extent of serous surface exposed to the drug.

Aged↗

The treatment of endometrial carcinoma: our experience in the period 1983-89.

The Authors evaluated 87 cases of endometrial carcinoma, of whom 65 (74.7%) at pathological stage I. The surgical ratio was (96.5% 84/87 cases), and 31 cases were subjected to adjuvant postsurgical Radiotherapy because of the presence of risk factors. The incidence of relapses resulted complessively in 14.2%, with a NED-survival of 86.1% and an overall survival of 91.9% at the pathological stage I. The Authors emphasise particularly the importance of post-surgical Radiotherapy in the cases at risk, which allowed an important decrease of the incidence of relapses at stage I with regard to previous studies.

Aged↗

Wertheim-Meigs operation in the Gynaecologic and Obstetric Institute of Sassari in the ten-year period 1980-89.

In a retrospective study we examined 42 radical hysterectomies according to Wertheim-Meigs in the ten year period 1980-89, of whom 39 for carcinoma of the cervix, two for endometrial carcinoma at stage II one for microinvasive vaginal carcinoma. The incidence of relapses was 11.9% (5 cases) globally, with 3.7% at pathologic stage I, while the actuarial survival was 95.4% at stage I. The intraoperative, perioperative and postactinic complications related to integrated treatment are described, underlining the importance of post-surgical Radiotherapy in cases at risk.

Female↗

Muscarinic and quisqualate receptor-induced phosphoinositide hydrolysis in primary cultures of striatal and hippocampal neurons. Evidence for differential mechanisms of activation.

Several neurotransmitters activate polyphosphoinositide (PPI) hydrolysis in CNS neurons as the first step of a transmembrane signalling cascade that may lead to neuronal circuit modulation. Muscarinic and quisqualate receptor-triggered PPI hydrolysis was investigated in neuronal primary cultures. A clear increase in inositol phosphates (Ins-Ps) was detected as early as 15 s after the agonist addition; at this time, the increases of inositol 1,4,5-trisphosphate (measured by HPLC) were relatively larger with respect to the other Ins-Ps. Ins-P accumulation was maintained in part in a Ca2+-free medium, excluding that Ca2+ entry is the fundamental step of the receptor-induced PPI hydrolysis. Acute cell pretreatment with phorbol dibutyrate, an activator of protein kinase C, was able to inhibit 50% of the response to carbachol, and almost completely the quisqualate effect, suggesting a negative feedback modulation by the enzyme. Finally, pertussis toxin failed to inhibit muscarinic responses, whereas it blocked greater than 70% of the quisqualate stimulation. The two receptors therefore appear coupled to phosphodiesterase by two different G proteins. The comparison of the results obtained by stimulating the two receptor systems suggests that the generation of the same intracellular signal at two distinct receptor types may occur by different coupling mechanisms, and be differently regulated even in the same neuronal preparations.

Animals↗

Evidence for a single glutamate receptor of the ionotropic kainate/quisqualate type.

The kainate (KA) and the quisqualate (QUIS) receptors that activate cation channels in the central nervous system have previously been defined as two of the major glutamate receptor types. In amphibian brain, an exceptionally rich source of these sites, they can be coextracted by octylglucoside and shown to behave as one entity in all analyses made in solution. When partly purified by lectin affinity, ion-exchange chromatography or by sucrose gradient centrifugation, the two activities comigrate in a 1:1 ratio. When the QUIS component is bound to an immobilized specific QUIS agonist, the KA component is extracted in parallel with it. There are equivalent numbers of the QUIS and KA sites and the two sites show a single affinity series for the binding of glutamatergic agonists. We deduce that KA or QUIS select different conformations of a single KA/QUIS receptor binding site, leading thus to the different channel-opening events that have been reported for these two agonists.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Second-messenger control of catecholamine release from PC12 cells. Role of muscarinic receptors and nerve-growth-factor-induced cell differentiation.

The role of various intracellular signals and of their possible interactions in the control of neurotransmitter release was investigated in PC12 cells. To this purpose, agents that affect primarily the cytosolic concentration of Ca2+, [Ca2+]i (ionomycin, high K+), agents that affect cyclic AMP concentrations (forskolin; the adenosine analogue phenylisopropyladenosine; clonidine) and activators of protein kinase C (phorbol esters) were applied alone or in combination to either growing chromaffin-like PC12-cells, or to neuron-like PC12+ cells differentiated by treatment with NGF (nerve growth factor). In addition, the release effects of muscarinic-receptor stimulation (which causes increase in [Ca2+]i, activation of protein kinase C and decrease in cyclic AMP) were investigated. Two techniques were employed to measure catecholamine release: static incubation of [3H]dopamine-loaded cells, and perfusion incubation of unlabelled cells coupled to highly sensitive electrochemical detection of released catecholamines. The results obtained demonstrate that: (1) release from PC12 cells can be elicited by both raising [Ca2+]i and activating protein kinases (protein kinase C and, although to a much smaller extent, cyclic AMP-dependent protein kinase); and (2) these various control pathways interact extensively. Activation of muscarinic receptors by carbachol induced appreciable release responses, which appeared to be due to a synergistic interplay between [Ca2+]i and protein kinase C activation. The muscarinic-induced release responses tended to become inactivated rapidly, possibly by feedback desensitization of the receptor mediated by protein kinase C. Muscarinic inactivation was prevented (or reversed) by agents that increase, and accelerated by agents that decrease, cyclic AMP. Agents that stimulate release primarily through the Ca2+ pathway (ionomycin and high K+) were found to be equipotent in both PC12- and PC12+ cells, whereas the protein kinase C activator 12-O-tetradecanoyl-phorbol 13-acetate was approx. 10-fold less potent in PC12+ cells, when administered either alone or in combination with ionomycin. In contrast, the cell binding of phorbol esters was not greatly modified by NGF treatment. Thus control of neurotransmitter release from PC12 cells is changed by differentiation, with a diminished role of the mechanism mediated by protein kinase C.

Adrenal Gland Neoplasms↗

HIV-related malignant lymphoma: a report of 46 cases observed in Italy.

We report 36 patients with non-Hodgkin's lymphomas (NHL) and 10 patients with Hodgkin's disease (HD), predominantly intravenous drug abusers (IVDA; 35 patients), diagnosed in 16 different Italian centers. The group of NHL has a median age of 26 years (range 16-64): 26 were IVDA, 3 polytransfused, 3 IVDA and homosexual men, 2 homosexual men and 2 without apparent risk for AIDS but carrying HIV antibodies. 81% of the evaluable patients had high-grade NHL (32% Burkitt's type) according to the Working Formulation, 15% intermediate and 4% low-grade. Out of 23 patients with stage reported, 16 (70%) were stage IV, 2 (9%) stage III, 1 (4%) stage II and 4 (17%) stage I (CNS involvement). The group with HD has a median age of 25 years (range 20-40), 9 were IVDA and 1 IVDA and homosexual. Of the 7 patients with subtype reported, 4 patients had nodular sclerosis and 3 mixed cellularity subtype. Stage III and IV were reported in 66% of the patients. The median survival is 4 months for NHL and 10 months for HD. The most common cause of death is opportunistic infection in 86% of the evaluable cases.

Acquired Immunodeficiency Syndrome↗

Malignant lymphomas in patients with or at risk for AIDS: a report of 50 cases observed in Italy.

For the first time the presence of a consistent number of malignant lymphomas among persons at high risk for AIDS has been documented in Italy. The majority of our cases started to occur in 1983, in line with the trend for a 2-year delay in the spread of the epidemic of AIDS in Europe. The patients with non-Hodgkin's lymphomas had an increased incidence of high grade subtypes, particularly of the Burkitt type, and were in an advanced stage with frequent extranodal involvement. Patients with Hodgkin's disease had a lower incidence of extranodal localization in comparison with the North American series. American patients with malignant lymphomas were reported to be predominantly homosexual; in contrast, the Italian cases were mostly drug addicts. The occurrence of malignant lymphomas was also correlated in Italian patients as well as in American patients with a shorter survival time, when compared with malignant lymphomas occurring in the same age group of the general population.

Acquired Immunodeficiency Syndrome↗

Activation of a muscarinic receptor selectively inhibits a rapidly inactivated Ca2+ current in rat sympathetic neurons.

Sympathetic neurons dissociated from the superior cervical ganglion of 2-day-old rats were studied by whole-cell patch clamp and by fura-2 measurements of the cytosolic free Ca2+ concentration, [Ca2+]i. Step depolarizations in the presence of tetrodotoxin and hexamethonium triggered two Ca2+ currents that differed in the voltage dependence of activation and kinetics of inactivation. These currents resemble the L and N currents previously described in chicken sensory neurons [Nowycky, M. C., Fox, A. P. & Tsien, R. W. (1985) Nature (London) 316, 440-442]. Treatment with acetylcholine resulted in the rapid (within seconds), selective, and reversible inhibition of the rapidly inactivated, N-type current, whereas the long-lasting L-type current remained unaffected. The high sensitivity to blocker drugs (atropine, pirenzepine) indicated that this effect of acetylcholine was due to a muscarinic M1 receptor. Intracellular perfusion with nonhydrolyzable guanine nucleotide analogs or pretreatment of the neurons with pertussis toxin had profound effects on the Ca2+ current modulation. Guanosine 5'-[gamma-thio]triphosphate caused the disappearance of the N-type current (an effect akin to that of acetylcholine, but irreversible), whereas guanosine 5'-[beta-thio]diphosphate and pertussis toxin pretreatment prevented the acetylcholine-induced inhibition. In contrast, cAMP, applied intracellularly together with 3-isobutyl-1-methylxanthine, as well as activators and inhibitors of protein kinase C, were without effect. Acetylcholine caused shortening of action potentials in neurons treated with tetraethylammonium to partially block K+ channels. Moreover, when applied to neurons loaded with the fluorescent indicator fura-2, acetylcholine failed to appreciably modify [Ca2+]i at rest but caused a partial blunting of the initial [Ca2+]i peak induced by depolarization with high K+. This effect was blocked by muscarinic antagonists and pertussis toxin and was unaffected by protein kinase activators. Thus, muscarinic modulation of the N-type Ca2+ channels appears to be mediated by a pertussis toxin-sensitive guanine nucleotide-binding protein and independent of both cAMP-dependent protein kinase and protein kinase C.

Acetylcholine↗

Female genital cancer incidence in the Province of Sassari from 1974 to 1983.

The incidence of gynaecologic tumours in the Province of Sassari has been studied in order to estimate their value and to make a comparison with the ones industrialised countries. The global incidence of uterine cancer (corpus uteri plus cervix) is of 18.16/100,000 women; 11.99/100,000 for cancers of corpus uteri and 6.17/100,000 for cervical carcinoma including in situ forms. The incidence of gynaecologic tumors for the District of Sassari is equivalent to that reported in Western countries and it does confirm indeed a constant and progressive increase in tumours of the corpus uteri and a reduction in cervical carcinoma especially if in situ forms are excluded.

Adolescent↗

Activation of muscarinic receptors in PC12 cells. Correlation between cytosolic Ca2+ rise and phosphoinositide hydrolysis.

The intracellular signals generated by carbachol activation of the muscarinic receptor [release of inositol phosphates as a consequence of phosphoinositide hydrolysis and rise of the cytosolic Ca2+ concentration ([Ca2+]i, measured by quin2)] were studied in intact PC12 pheochromocytoma cells that had been differentiated by treatment with nerve growth factor. When measured in parallel samples of the same cell preparation 30 s after receptor activation, the release of inositol trisphosphate and of its possible metabolites, inositol bis- and mono-phosphate, and the [Ca2+]i rise were found to occur with almost superimposable carbachol concentration curves. At the same time carbachol caused a decrease in the radioactivity of preloaded phosphatidylinositol 4,5-bisphosphate, the precursor of inositol trisphosphate. Neither the inositol phosphate nor the [Ca2+]i signal was modified by preincubation of the cells with either purified Bordetella pertussis toxin or forskolin, the direct activator of adenylate cyclase. Both signals were partially inhibited by dibutyryl cyclic AMP, especially when the nucleotide analogue was applied in combination with the phosphodiesterase inhibitors RO 201724 and theophylline. The latter drug alone profoundly inhibited the carbachol-induced [Ca2+]i rise, with only minimal effect on phosphoinositide hydrolysis. Because of the diverging results obtained with forskolin on the one hand, dibutyryl cyclic AMP and phosphodiesterase inhibitors on the other, the effects of the latter drugs are considered to be pharmacological, independent of the intracellular cyclic AMP concentration. Two further drugs tested, mepacrine and MY5445, inhibited phosphoinositide hydrolysis at the same time as the 45Ca2+ influx stimulated by carbachol. Taken together, our results concur with previous evidence obtained with permeabilized cells and cell fractions to indicate phosphatidylinositol 4,5-bisphosphate hydrolysis and [Ca2+]i rise as two successive events in the intracellular transduction cascade initiated by receptor activation. The strict correlation between the carbachol concentration curves for inositol trisphosphate generation and [Ca2+]i rise, and the inhibition by theophylline of the Ca2$ signal without major effects on inositol phosphate generation, satisfy important requirements of the abovementioned interpretation.

Adrenal Gland Neoplasms↗