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Showing papers by "University of Naples Federico II published in 1995"



Proceedings ArticleDOI
08 Dec 1995
TL;DR: The FM messaging primitives and the critical design issues in building a low-latency messaging layers for workstation clusters are described and detailed measurements show how each of these features contribute to high performance.
Abstract: In most computer systems, software overhead dominates the cost of messaging, reducing delivered performance, especially for short messages. Efficient software messaging layers are needed to deliver the hardware performance to the application level and to support tightly-coupled workstation clusters. Illinois Fast Messages (FM) 1.0 is a high speed messaging layer that delivers low latency and high bandwidth for short messages. For 128-byte packets, FM achieves bandwidths of 16.2MB/s and one-way latencies 32 µs on Myrinet-connected SPARCstations (user-level to user-level). For shorter packets, we have measured one-way latencies of 25 µs, and for larger packets, bandwidth as high as to 19.6MB/s — delivered bandwidth greater than OC-3. FM is also superior to the Myrinet API messaging layer, not just in terms of latency and usable bandwidth, but also in terms of the message half-power point (n_{\frac{1}{2}}), which is two orders of magnitude smaller (54 vs. 4,409 bytes). We describe the FM messaging primitives and the critical design issues in building a low-latency messaging layers for workstation clusters. Several issues are critical: the division of labor between host and network coprocessor, management of the input/output (I/O) bus, and buffer management. To achieve high performance, messaging layers should assign as much functionality as possible to the host. If the network interface has DMA capability, the I/Obus should be used asymmetrically, with the host processor moving data to the network and exploiting DMA to move data to the host. Finally, buffer management should be extremely simple in the network coprocessor and match queue structures between the network coprocessor and host memory. Detailed measurements show how each of these features contribute to high performance.

392 citations


Journal ArticleDOI
TL;DR: The alignment of the three APP encoding cDNA fragments found in the screening suggests that the region of APP involved in the binding is centered on the NPTY sequence, which is analogous to that present in the intracellular domains of the growth factor receptors interacting with the PID/PTB domain of Shc.

306 citations


Journal ArticleDOI
07 Apr 1995-Cell
TL;DR: The cloned region within Xp22.3 where the CDPX gene has been assigned and three adjacent genes showing highly significant homology to the sulfatase gene family are isolated suggest that warfarin embryopathy might involve drug-induced inhibition of the same enzyme.

288 citations


Journal ArticleDOI
TL;DR: Results show that an NO-releasing NSAID derivative and an NO donor could accelerate ulcer healing, whereas a standard NSAID, misoprostol, and two inhibitors of cyclooxygenase 2 had no effect.

280 citations


Journal ArticleDOI
TL;DR: A key role for ras is indicated in smooth muscle cell proliferation and the local delivery of transdominant negative mutants of ras in vivo might prevent some of the acute vascular injury caused by balloon injury.
Abstract: Proliferation of smooth muscle cells of the arterial wall in response to local injury is an important aetiologic factor of vascular proliferative disorders such as atherosclerosis and restenosis after angioplasty. Ras proteins are key transducers of mitogenic signals from membrane to nucleus in many cell types. We investigated the role of ras proteins in the vascular response to arterial injury by inactivating cellular ras of rats in which the common carotid artery was subjected to balloon injury. DNA vectors expressing ras transdominant negative mutants, which interfere with ras function, reduced neointimal formation after injury. Our results indicate a key role for ras in smooth muscle cell proliferation and show that the local delivery of transdominant negative mutants of ras in vivo might prevent some of the acute vascular injury caused by balloon injury.

257 citations


Journal ArticleDOI
TL;DR: Reversation of diastolic dysfunction in aortic stenosis takes years and is accompanied by a slow regression of interstitial fibrosis, whereas relaxation rate decreases with a reduction in left ventricular muscle mass.
Abstract: Background The remodeling of the left ventricle in patients with aortic stenosis after aortic valve replacement (AVR) is a complex process involving structural and functional changes Methods and Results Twenty-two patients were included in the present analysis Twelve patients with severe aortic stenosis were studied before surgery, early (22±8 months) and late (81±22 months) after AVR using left ventricular biplane angiograms, high-fidelity pressure measurements, and endomyocardial biopsies Ten healthy subjects were used as controls Left ventricular systolic function was assessed from biplane ejection fraction, and diastolic function from the time constant of relaxation, the peak filling rate, and the myocardial stiffness constant Left ventricular structure was evaluated from interstitial fibrosis, fibrous content, and muscle fiber diameter Left ventricular muscle mass was significantly increased before surgery in patients with aortic stenosis and remained increased early after surgery, although the

238 citations


Journal ArticleDOI
TL;DR: The results indicate that oxidative stress induces WAF1/CIP1 expression and arrests cell cycle progression through a mechanism that is independent of p53, which may provide for cell cycle checkpoint control under conditions that inactivate p53.

237 citations


Journal ArticleDOI
TL;DR: It is demonstrated that short- and long-term exposures of beta cells to high plasma NEFA concentrations have opposite effects on glucose-induced insulin secretion.
Abstract: Our study investigates short- and long-term effects of infusion of non-esterified fatty acids (NEFA) on insulin secretion in healthy subjects. Twelve healthy individuals underwent a 24-h Intralipid (10% triglyceride emulsion) infusion at a rate of 0.4 ml/min with a simultaneous infusion of heparin (a bolus of 200 U followed by 0.2 U/min per kg body weight). After an overnight fast (baseline), at 6 and at 24 h of Intralipid infusion and 24 h after Intralipid discontinuation (recovery test), all subjects underwent an intravenous glucose tolerance test (iv-GTT) (25 g of glucose/min). Intralipid infusion caused a threefold rise in plasma NEFA concentrations with no difference between the 6- and the 24-h concentrations. Compared to baseline acute insulin response (AIR) (AIR = 63 +/- 8 mU/l), short-term (6-h) Intralipid infusion was associated with a significant increase in AIR (86 +/- 12 mU/l p < 0.01); in contrast, long-term (24-h) Intralipid delivery was associated with inhibition of AIR (31 +/- 5 mU/l) compared to baseline (p < 0.001) and to the 6-h (p < 0.03) triglyceride emulsion infusion. Intralipid infusion was associated with a progressive and significant decline in respiratory quotient (RQ). A positive correlation between changes in fasting plasma NEFA concentrations and AIR at the 6-h infusion (r = 0.89 p < 0.001) was found. In contrast, at the end of the Intralipid infusion period, changes in plasma NEFA concentrations and AIR were negatively correlated (r = -0.87 p < 0.001). The recovery test showed that fasting plasma NEFA concentrations, RQ and AIR had returned to baseline values. In the control study (n = 8) 0.9% NaCl infusion did not mimick the effect of Intralipid. In conclusion, our study demonstrates that short- and long-term exposures of beta cells to high plasma NEFA concentrations have opposite effects on glucose-induced insulin secretion.

221 citations


Journal Article
19 Oct 1995-Oncogene
TL;DR: It is shown that both the V EGF receptors, FLT-1 and flk/KDR, are expressed in endothelial cells that line tumor-embedded microvascular vessels, suggesting that VEGF but not PlGF, contributes to thyroid tumor development.
Abstract: Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells in vitro, promotes neoangiogenesis in vivo and increases the permeability of the vascular endothelium. VEGF overexpression occurs in several cultured tumor cell lines and in certain human malignancies. Placenta growth factor (PlGF) is a recently identified growth factor for endothelial cells (EC); PlGF strongly potentiates both the proliferative and the permeabilization effects exerted by VEGF on the vascular endothelium. To uncover the molecular mechanisms underlying neoangiogenesis in human thyroid tumors, we have analysed VEGF and PlGF expression in a panel of thyroid carcinoma cell lines with different tumorigenic potential as well as in human primary thyroid tumors. We show that a high tumorigenic potential is associated with an elevated VEGF expression in human thyroid tumor cell lines. Furthermore, VEGF overexpression occurs in 5/5 highly malignant anaplastic carcinomas. Papillary and follicular carcinomas express intermediate levels of VEGF mRNA. In contrast, PlGF expression is severely down regulated in the majority of thyroid tumor cell lines and in tumors. Furthermore, we show that both the VEGF receptors, FLT-1 and flk/KDR, are expressed in endothelial cells that line tumor-embedded microvascular vessels, suggesting that VEGF but not PlGF, contributes to thyroid tumor development.

219 citations


Journal ArticleDOI
TL;DR: An immediate GFR decline proportional to the osmolarity of CM and secondary to the renal hypoperfusion that is neither caused by hypovolemia nor mediated by ET-1, an early tubular dysfunction at the level of the proximal nephron, and a protective effect of single-dose pretreatment with either captopril or nifedipine on D-induced acute and short-term GFR changes are found.
Abstract: The pathophysiology and prevention of contrast media (CM)-induced nephropathy in chronic renal failure (CRF) are still ill defined. GFR, RPF, endothelin-1 (ET-1) levels, urinary sodium concentration, and fractional excretion of sodium were measured in CRF patients undergoing water diuresis in basal conditions and 20 to 120 min after an iv bolus of either the high-osmolar CM diatrizoate (D) or the low-osmolar CM iopamidol (I). The two CM induced an immediate and progressive decline of both GFR and RPF in the absence of hypovolemia, more pronounced in D (-36% at 120 min) than after I (-19% at 120 min; P < 0.05 versus D). Both CM determined a marked and steady increase of the fractional excretion of sodium. The natriuresis could not be totally ascribed to a CM-induced osmotic diuresis as because the urinary sodium concentration markedly increased. In two further groups of patients receiving D, we studied the effects of pretreatment with a single dose of either captopril or nifedipine. Both drugs, although not preventing the increase of natriuresis, partially antagonized D-induced renal hypoperfusion: GFR and RPF were equally reduced by 20% in D/captopril and D/nifedipine (P < 0.05 versus D). In unpretreated patients receiving either D or I, plasma ET-1 did not change but urinary levels increased; these changes were, however, dissociated from those observed in renal hemodynamics. Both plasma and urinary levels of ET-1 did not vary in pretreated groups. The 72-h follow-up evidenced a significant reduction of renal function only in the unpretreated D group. Therefore, the main findings after CM administration in CRF patients are: (1) an immediate GFR decline proportional to the osmolarity of CM and secondary to the renal hypoperfusion that is neither caused by hypovolemia nor mediated by ET-1, (2) an early tubular dysfunction at the level of the proximal nephron, and (3) a protective effect of single-dose pretreatment with either captopril or nifedipine on D-induced acute and short-term GFR changes.

Journal ArticleDOI
15 Nov 1995-Cancer
TL;DR: The prognostic effect of lymphatic and blood vessel invasion (LVI and BVI) on survival in a retrospective sample of 1408 patients with breast cancer is assessed.
Abstract: Background. This study assessed the prognostic effect of lymphatic and blood vessel invasion (LVI and BVI) on survival in a retrospective sample of 1408 patients with breast cancer. Methods. Survival analysis was evaluated by univariate (Kaplan-Meier product limit method and log rank test) and multivariate (Cox model) analysis. Correlations among variables were studied by contingency tables and statistical significance was evaluated by chi-square test. Results. Lymphatic vessel invasion was present in 34.2% of cases, and BVI in 4.2%. Lymphatic vessel invasion correlated with BVI (P < 0.0001), and both were correlated with metastatic axillary lymph nodes and increasing tumor size and grade; BVI was sporadic (only 10 cases) among lymph node negative patients. Although LVI was more frequent among premenopausal patients and those with ductal carcinomas, BVI was unrelated to menopausal status and tumor type. Lymphatic vessel invasion and BVI were associated with poor survival by univariate analysis (P < 0.0001). By multivariate analysis, relative risk of death was significantly increased when LVI was present both in the whole series as well as in the lymph node negative and lymph node positive subgroups; the prognostic role of LVI was independent of menopausal and lymph node status, tumor size, tumor grade, or adjuvant treatment. In the lymph node negative sample, LVI had strong prognostic power. In the lymph node positive sample, the prognostic role of LVI was also independent of the number of lymph nodes with metastases. Blood vessel invasion had no prognostic role in any subgroup. Conclusion. The prevalence of BVI was particularly low in this study, and the question of its possible prognostic role for patients with breast cancer should be assessed with methods that amplify its detection. LVI is a strong prognostic factor for operable patients with breast cancer. In lymph node negative patients, LVI is a predictor of poor prognosis for those who are consequently candidates for adjuvant therapy. Similarly, in lymph node positive patients, LVI is a predictor for a high risk of death for those who are candidates for highly intensive adjuvant strategies. Cancer 1995; 76:1772–8.

Journal Article
TL;DR: Heart mast cells released histamine in response to immunologic and nonimmunologic stimuli but did not respond to substance P, FMLP, 12-O-tetradecanoylphorbol-13-acetate, or acetylcholine, and were a useful model with which to study the role of these cells and their mediators in cardiac anaphylaxis and cardiovascular diseases.
Abstract: We have isolated, partially purified, and characterized the mast cells from human heart tissue. The histamine content of left and right ventricles and septum of hearts obtained from 25 patients undergoing heart transplantation was 5.4 +/- 0.6, 5.3 +/- 0.5, and 5.6 +/- 0.5 micrograms/g of wet tissue, respectively. Ultrastructural study of cardiac mast cells revealed scroll, crystal, and mixed granules, homogeneously dense granules, and lipid bodies in the cytoplasm. A mild collagenase digestion was used to disperse the heart mast cells; the average yield was 3.2 +/- 0.6% (range: 0.8 to 13.6%). The average histamine and tryptase content/heart mast cells was 3.3 +/- 0.2 pg (n = 25) and 24.2 +/- 4.3 micrograms/10(6) cells (n = 11), respectively. Survival of cardiac mast cells after overnight culture was 71.9 +/- 5.4% (n = 23). The purification of human heart mast cells can be brought from less than 0.1 to 12% by a combination of low-speed centrifugation over albumin (2%) solution and Percoll gradient. Viability as shown by trypan blue exclusion was greater than 90%. Heart mast cells released histamine in response to immunologic (anti-IgE, anti-Fc epsilon RI, and C5a) and nonimmunologic stimuli (recombinant human stem cell factor, A23187, and compound 48/80) but did not respond to substance P, FMLP, 12-O-tetradecanoylphorbol-13-acetate, or acetylcholine. There was a linear correlation between the percentage of release caused by anti-IgE and anti-Fc epsilon RI, whereas there was no correlation between the release caused by C5a and anti-IgE-mediated stimuli. Cross-linking with anti-IgE of IgE on heart mast cells induced the release of tryptase (10.1 +/- 2.1 micrograms/10(7) cells; n = 10) and the de novo synthesis of PGD2 (17.3 +/- 4.3 ng/10(6) cells; n = 10) and of leukotriene C4 (19.1 +/- 4.5 ng/10(6) cells; n = 10). There was a linear correlation between the percentage of histamine secretion and tryptase release (r = 0.67; p < 0.001) induced by cross-linking of Fc epsilon RI. similarly, there was a significant correlation between percentage of histamine secretion and PGD2 (r = 0.63; p < 0.001) and LTC4 (r = 0.64; p < 0.001) release. Immunoelectron microscopy demonstrated the presence of chymase in cardiac mast cells. Mast cells isolated from human heart can be a useful model with which to study the role of these cells and their mediators in cardiac anaphylaxis and cardiovascular diseases.

Journal ArticleDOI
TL;DR: Chronic vitamin C administration has beneficial effects upon glucose and lipid metabolism in aged non-insulin dependent (type II) diabetic patients and is correlated with the percent decline in plasma free radicals and increase in GSH levels.
Abstract: Our study investigated the metabolic benefits deriving from chronic pharmacological vitamin C administration in aged non-insulin dependent (Type II) diabetic patients.Forty type II diabetic patients (age: 72 +/− 0.5 years) underwent placebo and vitamin C (0.5 g twice daily) administration in double-blind, randomized, cross-over fashion. All patients were treated by oral hypoglycaemic agents which continued throughout the study. After baseline observations, treatment periods lasted 4 months and were separated by a 30-day wash-out period.Patients' antropometric data were unchanged throughout the study. Chronic vitamin C administration vs placebo was associated with a significant decline in fasting plasma free radicals (0.26 +/− 0.06 vs 0.49 +/− 0.07 p < 0.03) and insulin (90 +/− 4 vs 73 +/− 6 pmol/L p < 0.04), total- (7.3 +/− 0.5 vs 5.8 +/− 0.4 mmol/L p < 0.03), LDL-cholesterol (5.6 +/− 0.6 vs 4.1 +/− 0.3 mmol/L p < 0.05) and triglycerides (2.58 +/− 0.07 vs 2.08 +/− 0.04 mmol/L p < 0.04) levels. In 20 patie...

Journal ArticleDOI
TL;DR: It is demonstrated that NO increases prostaglandin biosynthesis in vivo through a guanosine 3′:5′‐cyclic monophosphate (cyclic GMP)‐independent mechanism and suggested that the interaction between NO synthase and cyclo‐oxygenase (COX) pathways may represent an important mechanism for the modulation of the inflammatory response.
Abstract: 1. Modulation of prostaglandin biosynthesis in vivo by either exogenous or endogenous nitric oxide (NO) has been studied in the rat using arachidonic acid (AA)-induced paw oedema and measuring both the foot volume and the amount of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolite of prostacyclin (PGI2), in the oedematous fluid recovered from inflamed paws. 2. Paw injections of 150 or 300 nmol of AA were virtually inactive whereas 600 nmol produced a moderate oedema which was greatly reduced by the NO synthase inhibitor L-NG-nitro arginine methyl ester (L-NAME, 100 nmol/paw) and the NO scavenger haemoglobin (Hb, 30 mumol/paw), but unaffected by the inhibitor of the soluble guanylate cyclase, methylene blue (Mb, 3 mumol/paw) and L-arginine (15 mumol/paw). 3. The NO-donors (10 mumol/paw) 3-morpholino-sydnonimine-hydrochloride (SIN-1), S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and sodium nitroprusside (SNP) significantly potentiated the paw oedema induced by AA (300 nmol/paw). 4. SIN-1 (2.5, 5 and 10 mumol/paw) produced a significant dose-dependent increase of the oedema induced by AA which was correlated with increased amounts of 6-keto-PGF1 alpha in the fluid recovered from inflamed paws. 5. Both oedema and prostaglandin biosynthesis induced by the combination AA+SIN-1 were greatly suppressed by either Hb (30 mumol/paw) or indomethacin (3 mumol/paw or 5 mg kg-1 s.c.) but unaffected by Mb (3 mumol/paw).(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
TL;DR: These results confirm the high prevalence of adverse reactions to foods in diarrheic irritable bowel syndrome and the usefulness of cromolyn sodium treatment in these patients.
Abstract: Background: In a significant number of patients affected by the irritable bowel syndrome, an adverse reaction to food is proposed to be a causative factor. A diet that eliminates the offending food...

Journal ArticleDOI
01 Apr 1995-Stroke
TL;DR: Significant relationships between carotid artery ultrasound plaque characteristics and ischemic cerebrovascular events are demonstrated and encourage further prospective studies in asymptomatic subjects focused on echographicCarotid plaque characteristics as predictors of subsequent TIA or stroke.
Abstract: Background and Purpose Atherosclerotic plaques in extracranial carotid arteries, particularly in the bifurcation of the common carotid and internal carotid arteries, may cause transient cerebral ischemia and stroke by lumen stenosis or plaque-related thromboembolism. B-mode ultrasound imaging has the capability of providing information on plaque thickness, characteristics, and location in carotid arteries. Methods A retrospective analysis of 242 stroke and 336 transient ischemic attack (TIA) patients, recruited for the B-Scan Ultrasound Imaging Assessment Program, was performed to determine the ultrasonographic correlates of carotid atherosclerosis and acute cerebral ischemia. A matched case-control study design was used to compare brain hemispheres with ischemic lesions (“cases”) to unaffected contralateral hemispheres (“controls”) with regard to the presence and characteristics of carotid artery plaques. Results The first set of analyses examined the association between the presence of carotid plaques ipsilateral to the brain lesion and the occurrence of stroke or TIA and showed an association with recent episodes of TIA and stroke (odds ratio [OR], 1.6; P =.03) but not with past episodes. In a subset (n=232) of patients with plaques in both carotid arteries and recent cerebral ischemic events, stroke was associated with ipsilateral carotid artery occlusion ( P =.02). Lumen measurements at the site of the minimum residual lumen (MRL) diameter showed a significant association between a narrower lumen diameter in the carotid artery ipsilateral to case hemisphere and stroke (difference, 1.0 mm; P =.0003). TIA patients showed an association between both hypoechoic carotid plaques (OR, 3.0; P =.005) and the presence of longitudinal lesion motion (OR, 3.0; P =.02) with ipsilateral brain involvement. Plaque thickness at the MRL was positively correlated with both ipsilateral TIA (ipsilateral side, 4.4±0.15 mm; contralateral side, 3.9±0.16 mm; P =.007) and stroke (ipsilateral side, 4.2±0.23 mm; contralateral side, 3.3±0.21 mm; P =.0006). Conclusions These data demonstrate significant relationships between carotid artery ultrasound plaque characteristics and ischemic cerebrovascular events. These findings encourage further prospective studies in asymptomatic subjects focused on echographic carotid plaque characteristics as predictors of subsequent TIA or stroke.

Journal ArticleDOI
TL;DR: Two tris-indole alkaloids have been isolated for the first time from a marine source, the New Caledonian sponge, and showed anti-serotonin activity and a strong affinity for somatostatin and neuropeptide Y receptors in receptor-binding assays.
Abstract: Two tris-indole alkaloids, (+/-) gelliusines A and B [1], have been isolated for the first time from a marine source, the New Caledonian sponge, Orina sp. (or Gellius sp.), along with five further indole constituents [2-6]. Compound 6 has been identified as 2,2-bis-(6'-bromo-3'-indolyl(-ethylamine, previously isolated from the tunicate Didemnum candidum, but the remaining four indoles [2-5] are novel compounds. These showed anti-serotonin activity and a strong affinity for somatostatin and neuropeptide Y receptors in receptor-binding assays.

Journal ArticleDOI
TL;DR: It is found that VAO is able to reduce synthetic quinones, laccase-generated quinonoids, and phenoxy radicals with concomitant oxidation of veratryl alcohol to ver atryl aldehyde and reduced the molecular weight of soluble lignosulfonates to a significant extent.

Journal ArticleDOI
TL;DR: Despite differences in associated hemodynamic responses to various stress tests, a close relation exists between stenosis severity and diastolic perfusion time at the onset of stress-induced myocardial ischemia.
Abstract: Background Experimental studies have demonstrated that during stress-induced myocardial ischemia, coronary obstruction and diastolic perfusion time are factors that limit subendocardial perfusion and correlate to degree of myocardial dysfunction. The relation between these two factors has not yet been investigated in humans. The aim of the present study was to assess the relation between diastolic perfusion time and degree of coronary stenosis during different types of stress tests. Methods and Results Nine patients with isolated and proximal stenosis of the left anterior descending coronary artery were selected. Patients underwent three different randomized stress tests (upright, supine bicycle stress test, and transesophageal atrial pacing). Diastolic perfusion time, heart rate (RR interval), and systolic and diastolic pressures were measured during the test and at the ischemic threshold (0.1-mV ST-segment depression). Angiographic measurements of coronary stenosis were evaluated by quantitative coronar...

Journal ArticleDOI
TL;DR: Epidermal growth factor receptor receptor levels were evaluated in paraffin-embedded tumour specimens of non-small cell lung cancer (NSCLC) from 176 patients who underwent surgical resection and EGFr immunoreactivity was significantly higher in squamous than in non-squamous cell carcinomas.

Journal ArticleDOI
TL;DR: It is confirmed that cardiac dysfunction is a primary feature of Becker muscular dystrophy and that a real, dilated cardiomyopathy is the most frequent type of myocardial involvement after the age of 20.
Abstract: To evaluate the features and the course of cardiomyopathy in Becker muscular dystrophy, 68 patients–identified by clinical assessment and by reduced dystrophin labeling and/or DNA analysis–were followed in the years 1976–1993, for periods ranging from 3 to 18 years (mean 8). Patients periodically underwent clinical, electrocardiographic, echocardiographic, nuclear, and radiological assessments. Preclinical cardiac involvement was found in 67.4% of patients under 16 years of age, decreasing to 30% in patients older than 40. Clinically evident cardiomyopathy was found in 15% of patients under 16 years of age, increasing to 73% in patients older than 40. A real, dilated cardiomyopathy is the most frequent type of myocardial involvement after the age of 20. Results show that the severity of cardiac involvement can be unrelated to the severity of skeletal muscle damage and confirm that cardiac dysfunction is a primary feature of Becker muscular dystrophy.© 1995 John Wiley &Sons, Inc.

Journal ArticleDOI
TL;DR: Dmt-Tic opioidmimetic peptides represent a highly potent class of opioid peptide antagonists with greater potency than the nonopioid δ antagonist naltrindole and have potential application as clinical and therapeutic compounds.
Abstract: Tyr-Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) and Tyr-Tic-Ala were the first peptides with δ opioid antagonist activity lacking Phe, considered essential for opioid activity based on the N-terminal tripeptide sequence (Tyr-d-Xaa-Phe) of amphibian skin opioids. Analogs were then designed to restrain the rotational flexibility of Tyr by the substitution of 2,6-dimethyl-l-tyrosine (Dmt). Tyr and Dmt peptides were synthesized by solid phase and solution methods using Fmoc technology or condensing Boc-Dmt-OH or Boc-Tyr(But)-OH with H-l-Tic-OBut or H-d-Tic-OBut, respectively. Peptides were purified (>99%) by HPLC and characteristics determined by 1H-NMR, FAB-MS, melting point, TLC, and amino acid analyses. H-Dmt-Tic-OH had high affinity (Kiδ = 0.022 nM) and extraordinary selectivity (Kiμ/Kiδ = 150,000); H-Dmt-Tic-Ala-OH had a Kiδ = 0.29 nM and δ selectivity = 20,000. Affinity and selectivity increased 8700- and 1000-fold relative to H-Tyr-Tic-OH, respectively. H-Dmt-Tic-OH and H-Dmt-Tic-NH2 fitted one-site receptor binding models (η = 0.939−0.987), while H-Dmt-Tic-ol, H-Dmt-Tic-Ala-OH and H-Dmt-Tic-Ala-NH2 best fitted two-site models (η = 0.708−0.801, F 18.9−26.0, p 10 µM) in guinea-pig ileum preparations. Dmt-Tic analogs weakly interacted with κ receptors in the 1 to >20 µM range. Dmt-Tic opioidmimetic peptides represent a highly potent class of opioid peptide antagonists with greater potency than the nonopioid δ antagonist naltrindole and have potential application as clinical and therapeutic compounds.

Journal ArticleDOI
TL;DR: In this article, the ternary system of calcium sulfoaluminate (C4A3S), calcium sulfosilicate (C5S2S) and anhydrite (CS), synthesised by single firing at 1200 °C, was investigated.

Journal ArticleDOI
TL;DR: Some 68 plant extracts from 65 species belonging to 25 families were investigated for antibacterial activity against eight gram‐positive and gram‐negative bacteria and among the active extracts, 12 from 11 species exhibited a broad spectrum of activity.
Abstract: Some 68 plant extracts from 65 species belonging to 25 families were investigated for antibacterial activity against eight gram-positive and gram-negative bacteria. Of the 68 extracts, 64 (94.1%) exhibited inhibitory effects against one or more microorganisms. Furthermore, among the active extracts, 12 from 11 species exhibited a broad spectrum of activity. Discussion on the probable chemical components responsible for this activity is included.

Journal ArticleDOI
TL;DR: A new toxic sesterterpene, named fusaproliferin, was purified from corn kernel cultures of a strain of Fusarium proliferatum isolated from corn ear rot in northern Italy, and it is the first sester terpene isolated from a FUSarium species.
Abstract: A new toxic sesterterpene, named fusaproliferin, was purified from corn kernel cultures (120 mg/kg dry culture) of a strain of Fusarium proliferatum isolated from corn ear rot in northern Italy. The stain, designated ITEM-1494, also produced fumonisin B1 (1.500 mg/kg dry culture) and beauvericin (90 mg/kg dry culture), but not moniliformin. To monitor toxicity, the brine shrimp assay was used throughout the isolation procedure. Fusaproliferin had a molecular formula of C27H40O5, and it is the first sesterterpene isolated from a Fusarium species.

Journal ArticleDOI
TL;DR: Criteria for evaluating the classification reliability of a neural classifier and for accordingly making a reject option are proposed, and the method has been tested with a neuralclassifier devised for handprinted and multifont printed characters, by using a database of about 300000 samples.
Abstract: Criteria for evaluating the classification reliability of a neural classifier and for accordingly making a reject option are proposed. Such an option, implemented by means of two rules which can be applied independently of topology, size, and training algorithms of the neural classifier, allows one to improve the classification reliability. It is assumed that a performance function P is defined which, taking into account the requirements of the particular application, evaluates the quality of the classification in terms of recognition, misclassification, and reject rates. Under this assumption the optimal reject threshold value, determining the best trade-off between reject rate and misclassification rate, is the one for which the function P reaches its absolute maximum. No constraints are imposed on the form of P, but the ones necessary in order that P actually measures the quality of the classification process. The reject threshold is evaluated on the basis of some statistical distributions characterizing the behavior of the classifier when operating without reject option; these distributions are computed once the training phase of the net has been completed. The method has been tested with a neural classifier devised for handprinted and multifont printed characters, by using a database of about 300000 samples. Experimental results are discussed. >

Journal ArticleDOI
TL;DR: The visual language compiler-compiler (VLCC) system to automatically generate visual programming environments is developed, a grammar based system that can support implementation of any visual language by assisting the language designer in defining the language's graphical objects, syntax, and semantics.
Abstract: We have developed the visual language compiler-compiler (VLCC) system to automatically generate visual programming environments. VLCC is a grammar based system that can support implementation of any visual language by assisting the language designer in defining the language's graphical objects, syntax, and semantics. The final result of the generation process includes an integrated environment with a visual editor and a compiler for the defined visual language. In VLCC, graphical tools define visual languages to create both graphical objects and composition rules. Visual editors enable language designers to directly and visually manipulate the syntax of these languages. To capture the widest range of visual languages, the VLCC system can be configured for a specific language class. Different language classes can be characterized depending on their graphical objects' structure and on the way they can be composed. Also, box and arrow diagrams are defined for primitive objects with attaching points and for composition rules to join boxes and arrows at those attaching points. After choosing the visual language type to create, the designer can concentrate on language definition details. VLCC uses the positional grammar model as its underlying grammar formalism. >

Journal ArticleDOI
TL;DR: The results, obtained by analyzing the salt tolerance model of Maas-Hoffman and its descriptive parameters, place lettuce, endive and fennel in the moderately sensitive category.

Journal ArticleDOI
TL;DR: It was found that cytochalasin D almost completely inhibited internalization of all bacterial strains, whereas colchicine had no effect, indicating that host microfilaments play a major role in bacterial internalization.