6,727 research outputs found
Introduzione
No full textQuesto volume si propone di fornire un quadro aggiornato degli studi tipologici, superando il dualismo tra didattica e ricerca. Esso si configura certamente come uno strumento utile nella formazione avanzata, ma ambisce a essere anche un riferimento utile a chi si avvicini alla tipologia per esigenze di ricerca.
Il volume si divide in due parti. Nella prima viene tracciato il quadro teorico che fa da sfondo, oggi, agli studi tipologici. La seconda è invece dedicata alla presentazione di alcune applicazioni della tipologia linguistica
Come fare tipologia con categorie non tradizionali?
No full textL’articolo affronta una questione metodologica finora poco discussa all’interno degli studi di tipologia, ovvero come fare ricerca tipologica quando il fenomeno che ci si propone di studiare non fa parte della descrizione grammaticale tradizionale. La riflessione su questo tema nasce all’interno del progetto universaLIST, che mira a investigare le caratteristiche formali e funzionali delle ‘costruzioni a lista’ (Masini, Mauri & Pietrandrea 2018) nelle lingue del mondo. Il fenomeno ‘lista’ come qui inteso è, infatti, di difficile investigazione a livello tipologico, trattandosi di un concetto ‘non tradizionale’ e complesso, poiché trasversale rispetto ai tradizionali livelli di analisi. Nell’articolo proponiamo un metodo d’indagine multi-livello che affianca la ricerca tipologica classica basata sulle grammatiche esistenti con analisi più mirate basate su corpora di piccole e grandi dimensioni, consentendo così di massimizzare la possibilità di identificare pattern rilevanti e di individuare interessanti parallelismi tra lingue tipologicamente e genealogicamente distanti
Reduced sensitivity of fa/fa Zucker rats to adrenomedullin
No full textRat adrenomedullin is a peptide vasodepressor that may be of importance in the pathogenesis of hypertensive disease. Because of the known link between obesity and hypertension, we hypothesized that decreased responsiveness to adrenomedullin might be seen in an obese rodent model. In this study, the in vivo vasodilator actions of exogenous adrenomedullin were compared in anesthetized lean (n = 7) and obese (fa/fa) Zucker rats (n = 8). Adrenomedullin dose dependently lowered mean arterial pressure in both phenotypes, but the half-maximal dose (ID50) was 2-fold higher in fa/fa rats (1.7 +/- 0.22 vs. 0.83 +/- 0.06 nmol/kg). Moreover, the duration of effect was markedly reduced in the fa/fa rats, to 1-2 min from about 5 min in the lean animals. There was no evidence for an increased rate of degradation of adrenomedullin in the fa/fa rats. Although the rats used in this study were not hypertensive, adrenomedullin had reduced sensitivity and duration of action. The evidence suggests possible defects at the target receptor or altered metabolism of adrenomedullin in obesity.LR: 20061115; PUBM: Print; JID: 0372712; 0 (Peptides); 0 (Vasodilator Agents); 148498-78-6 (Adrenomedullin); ppublishSource type: Electronic(1
Identification of biochemical defects in pancreatic islets of fa/fa rats: a developmental study
No full textAdult obese (fa/fa) Zucker rats hypersecrete insulin in response to glucose and other secretagogues. Functional changes in islet alpha 2-adrenoceptors (8) and glycolytic regulation (9) have been reported. In this study, the development of these biochemical lesions in islets isolated from suckling (3 week old) and weanling (5 week old) lean and fa/fa rats was investigated and compared to results in adult animals. Glucose (15 mM)-induced insulin secretion was inhibited by mannoheptulose (MH) in lean (n = 8) but not fa/fa (n = 10) adult rats, indicating loss of sensitivity of glucokinase to competitive inhibition. Sensitivity to MH was somewhat reduced in the islets of 3- and 5-week-old fa/fa (n = 7 and 12) compared to lean (n = 15 and 9) rats, requiring 30-100 fold higher concentrations to achieve significant inhibition. At 3 weeks of age fa/fa rats did not differ from lean controls in either islet insulin content or body weight, but both parameters were increased in fa/fa rats by 5 weeks. The presence of altered alpha 2-adrenoceptor function in fa/fa rats could not be confirmed in this study. Unlike the previous report, prazosin did not antagonize alpha 2-agonist mediated inhibition of insulin secretion. The presence of defective regulation of the glycolytic pathway by mannoheptulose in suckling and weanling rats may contribute to development of hyperinsulinemia in fa/fa rats.LR: 20061115; PUBM: Print; JID: 9305691; 0 (Receptors, Adrenergic, alpha); 11061-68-0 (Insulin); 50-99-7 (Glucose); 654-29-5 (Mannoheptulose); EC 2.7.1.2 (Glucokinase); ppublishSource type: Electronic(1
Effect of adrenalectomy on the development of a pancreatic islet lesion in fa/fa rats
No full textAdrenalectomy prevents development of obesity and hyperinsulinaemia in obese (fa/fa) Zucker rats, thereby implicating the hypothalamo- pituitary-adrenal axis in the pathogenesis of obesity. In this study glucose-induced insulin secretion and glucokinase activity were investigated in isolated islets from adrenalectomized and control obese and lean female rats. Islets from control fa/fa rats were more sensitive to glucose with a half-maximal effective concentration (EC50) of 6.1 +/- 2.0 mmol. 1(-1) compared with 10.6 +/- 2.7 mmol. 1(-1) for adrenalectomized fa/fa rat islets. Adrenalectomy did not alter the islet sensitivity to glucose in the lean rats (EC50 of 9.4 +/- 1.5 mmol.1(-1) and 9.3 +/- 2.0 mmol. 1(-1) for adrenalectomized and control lean rats respectively). Mannoheptulose did not inhibit insulin secretion from control obese rats; however at concentrations of 1.0 mmol. 1(-1) or more it significantly inhibited glucose-induced insulin secretion in adrenalectomized obese and lean, and control lean rat islets (P < 0.05). In adrenalectomized fa/fa islets the glucokinase Km was increased twofold compared with the control fa/fa rats (9.5 +/- 1.5 mmol. 1(-1) vs 5.0 +/- 1.5 mmol. 1(-1), respectively), but there was no significant change in glucokinase Km in the lean rat islets after adrenalectomy. Mannoheptulose (10 mmol.1(-1) caused a significant reduction in glucose phosphorylation in disrupted islets of adrenalectomized fa/fa and lean, and of control lean rats, but not of control fa/fa rats. These data demonstrate that development of abnormal regulation of glycolysis in pancreatic islet beta cells of fa/fa rats, as indicated by the insulin response to manno-heptulose and glucokinase activity, is dependent on an intact hypothalamo-pituitary-adrenal axis.LR: 20061115; PUBM: Print; JID: 0006777; 0 (Blood Glucose); 11061-68-0 (Insulin); 50-22-6 (Corticosterone); 50-99-7 (Glucose); 654-29-5 (Mannoheptulose); EC 2.7.1.1 (Hexokinase); EC 2.7.1.2 (Glucokinase); ppublishSource type: Electronic(1
Ultrastructural and secretory heterogeneity of fa/fa (Zucker) rat islets
No full textMany previous studies of obese rodents documented biochemical changes in pancreatic islets that contribute to hyperinsulinemia in vivo. Those studies used heterogeneous populations of islets, although the size of islets from obese rats ranges from 500 microm. Here, functional and morphological changes in size-sorted ( 250 microm diameter) islets from obese Zucker (fa/fa) rats were correlated. Ultrastructural examination revealed that > 250 microm cultured islets had an increased number of immature secretory granules in the beta cells. The number of degranulated beta cells in > 250 and 250 microm, 250 microm islets compared with small islets. Studies of individual beta cells by reverse hemolytic plaque assay revealed 3-fold more cells from > 250 microm islets were stimulated by 1.4 mmol.l(-1) glucose than cells from < 125 microm islets. We conclude that functional defects in mixed size populations of islets from fa/fa rats are mainly due to alterations in the large islets, whereas smaller islets have relatively normal function. Exposure to high glucose exacerbates morphological and functional differences of large islets, which could have important implications in the transition to noninsulin-dependent diabetes when beta cell insulin production is unable to compensate for hyperglycemia.LR: 20061115; PUBM: Print; JID: 7500844; 11061-68-0 (Insulin); 50-99-7 (Glucose); 654-29-5 (Mannoheptulose); 7782-44-7 (Oxygen); ppublishSource type: Electronic(1
Evidence for defective glucose sensing by islets of fa/fa obese Zucker rats
No full textThe hypothesis that a defect in glucose sensing by islets of fa/fa Zucker rats contributes to hyperinsulinemia in these animals was tested. Islets from lean and fa/fa rats were isolated by collagenase digestion and step-density gradient purification and then cultured overnight in Dulbecco's modified Eagle's medium containing 12.5 mM glucose. Obese rat islets were more sensitive to hypoglycemic glucose levels with half-maximal effective concentration (EC50) of 5.6 mM compared with an EC50 of 8.2 mM for lean rat islets. In contrast, responsiveness of both phenotypes to alpha-ketoisocaproate and quinine was similar. Mannoheptulose did not inhibit insulin secretion from fa/fa islets, although inhibitors of later events in the stimulus-secretion coupling pathway were normally inhibited by iodoacetate and diazoxide. Finally, starvation in vivo and culture of islets in low glucose concentrations (5 mM) in vitro both decreased glucose-stimulated insulin secretion from lean but not fa/fa rat islets. We conclude that fa/fa rat islets have an exaggerated insulin response to hypoglycemic stimuli, possibly as a result of a defect in B-cell glucokinase function.LR: 20061115; PUBM: Print; JID: 0372712; 0 (Amino Acids); 0 (Blood Glucose); 0 (Iodoacetates); 11061-68-0 (Insulin); 130-95-0 (Quinine); 364-98-7 (Diazoxide); 50-99-7 (Glucose); 56-65-5 (Adenosine Triphosphate); 64-69-7 (Iodoacetic Acid); 654-29-5 (Mannoheptulose); EC 2.7.1.2 (Glucokinase); ppublishSource type: Electronic(1
p53 and c-erbB-2 protein expression in breast carcinomas. An immunohistochemical study including correlations with receptor status, proliferation markers, and clinical stage in human breast cancer
No full textFunctional characterization of alpha-adrenoceptors on pancreatic islets of fa/fa Zucker rats
No full textRecently, a defect in pertussis toxin-independent actions of epinephrine on pancreatic B-cells of fa/fa Zucker rats was reported (Cawthorn and Chan (1991) Mol. Cell. Endocrinol. 75, 197-204). We now report studies of islet alpha 2-adrenoceptor function of fa/fa rats. Insulin and cAMP production by islets of obese rats were both inhibited by the alpha 2-adrenoceptor agonist clonidine. Calculated pD2 values for clonidine were 9.57 +/- 0.59 and 9.43 +/- 0.33 for lean and fa/fa rat islets, respectively. Yohimbine reversed clonidine effects equipotently in lean and obese rat islets (pA2 values of 7.48 +/- 0.57 vs 7.43 +/- 0.58). Unexpectedly, the alpha 1-antagonist prazosin stimulated insulin secretion from islets of obese but not lean rats. Functional characteristics of the alpha-adrenoceptors on fa/fa islets are thus similar to those recently designated alpha 2B. Altered expression of alpha-adrenoceptors on pancreatic islets of fa/fa rats may contribute to changes in the pertussis toxin-independent pathway of epinephrine action previously observed.LR: 20061115; PUBM: Print; JID: 7500844; 0 (Receptors, Adrenergic, alpha); 11061-68-0 (Insulin); 146-48-5 (Yohimbine); 19216-56-9 (Prazosin); 4205-90-7 (Clonidine); 50-99-7 (Glucose); 51-43-4 (Epinephrine); 60-92-4 (Cyclic AMP); 66428-89-5 (Forskolin); ppublishSource type: Electronic(1
The expression of Axl receptor tyrosine kinase influences the tumour phenotype and clinical outcome of patients with malignant pleural mesothelioma
No full textBACKGROUND:
Recent preclinical studies identified Axl, a tyrosine kinase receptor implicated in tumour progression and epithelial-to-mesenchymal transition, as a putative therapeutic target in malignant pleural mesothelioma (MPM), an invariably fatal malignancy with limited treatment options. Here, we studied the expression of Axl and its ligand Gas-6 (growth arrest signal-6) in primary specimens of MPM, correlating their expression levels with tumour phenotype and clinical outcomes.
METHODS:
Two independent cohorts of consecutive patients diagnosed with MPM were studied: a derivation cohort composed of 63 cases and a validation set of 35 cases. Clinical variables including patients' demographics, tumour stage, histotype, performance status (PS), Axl and Gas-6 staining were tested for predicting overall survival (OS) using univariate and multivariate analyses.
RESULTS:
In the derivation cohort, Axl (P=0.001) but not Gas-6 overexpression (P=0.35) emerged as a univariate prognostic factor for OS, together with stage (P=0.05), PS (P<0.001) hypoalbuminaemia (P<0.001) and anaemia (P<0.001). Multivariate analyses confirmed Axl overexpression (P=0.01), PS (P=0.01), hypoalbuminaemia (P<0.001) and anaemia (P=0.04) as independent predictors of OS. The prognostic role of Axl overexpression was externally validated in an independent cohort (P=0.03).
CONCLUSION:
Overexpression of Axl is found in the majority of MPM specimens and influences patient's survival independently from other established prognostic factors. Such information may support patient selection for future trials
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