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101.
Letizia Mazzini Daniela Testa Carla Balzarini Gabriele Mora 《Journal of neurology》1994,241(4):223-227
Based on the hypothesis that free radicals play a general role in the neurodegenerative process in motor neuron disease, we tested selegiline in a group of patients affected by amyotrophic lateral sclerosis (ALS) to examine whether it might modify the progression of the disease. Patients were admitted if they were 25–80 years old and had a confirmed diagnosis of ALS with symptoms lasting no longer than 24 months. Patients with familial ALS, pure progressive bulbar palsy, primary lateral sclerosis or progressive muscle atrophy were excluded; a total of 111 patients were recruited. Fifty-three patients were randomly assigned to receive the drug (selegiline 10 mg/day orally for 6 months) and the remaining 58 were considered ALS controls. Mortality was similar in the two groups (4 and 5 patients respectively), though the difference was not statistically significant. Among the survivors, mean MRC and Norris disability scores and forced vital capacity were fairly similar in the two groups at all times and no statistically significant difference between treated and untreated patients was found. The results did not change when the data were related to age, duration and characteristics of onset of the disease. The rate of progression was significantly more rapid in patients with bulbar symptoms in both groups. Our data do not show any significant effect of selegiline in modifying the progression of ALS. 相似文献
102.
Argininosuccinic acid synthetase deficiency (ASD) is a rare disorder of urea cycle metabolism, with pronounced citrullinemia
and orotic aciduria being characteristic biochemical features. To further investigate the role of plasma orotic acid and its
possible use for monitoring the metabolic status in ASD, we determined plasma orotic acid, amino acid, and ammonium levels
in plasma samples collected over a period of 3 years from a patient who is now 8 years of age. Orotic acid plasma concentrations
varied widely from less than 1 μmol/l to more than 60 μmol/l. The renal clearance of orotic acid was eightfold the glomerular
filtration rate, thus supporting an active mechanism underlying the excretion of this pyrimidine. Data obtained during a metabolic
crisis yielded a statistically significant linear correlation of orotic acid plasma levels with those of glutamine and ammonium,
which are generally accepted for assessment of the successful treatment of this disorder. Our data revealed no advantage of
plasma orotic acid concentrations over the established amino acids (glutamine and arginine) and ammonium for determining acute
treatment responses. Since several effects of high levels of orotic acid have been described in mammals, further research
is necessary to assess a possible contribution of orotic acid to the pathogenesis of ASD and the use of plasma orotic acid
levels in the long-term monitoring of these patients.
Received: 3 November 1998 / Revised: 3 May 1999 / Accepted: 3 May 1999 相似文献
103.
Salvatore Squarcione Maria G. Pompa Daniela D'Alessandro 《European journal of epidemiology》1999,15(7):685-687
In 1994, the Italian Ministry of Health implemented a National Surveillance System to obtain data on the incidence of bacterial meningitis and its causative agents, including Haemophilus influenzae type b (Hib). As a consequence, case reporting of Hib meningitis is increasing year by year; in 1996, there were 126 notifications, of which 73% were in children under 2 years of age. Although underreporting still exists, parallel prospective or retrospective epidemiological surveys conducted in some Italian Regions allowed for partial correction of the incidence of Hib meningitis (up to 18.5/100,000 population in 1994). 相似文献
104.
Septo-optic dysplasia and growth hormone deficiency: accelerated pubertal maturation during GH therapy 总被引:1,自引:0,他引:1
Susanna Freude H Frisch Daniela Wimberger Edith Schober Gabriele Häusler F Waldhauser F Aichner 《Acta paediatrica (Oslo, Norway : 1992)》1992,81(8):641-645
We report four patients (three male, one female) with septo-optic dysplasia and growth hormone deficiency. All had GH therapy for a period of four to eight years until reaching final height. In all four cases bone maturation during puberty was accelerated (1.4 to 1.9 "years"/year), resulting in a final height which was clearly below the predicted height. The progress of pubertal stages was very short in all patients. In three patients TSH and prolactin release after TRH stimulation were increased. These data support a hypothalamic original of the endocrine disorder. Insufficient GH release, even after repeated GHRH stimulation, is in contrast to this assumption. In one case there was a late manifestation of neurohormonal diabetes insipidus, which indicates the possibility of later disease progression. MR imaging of the brain demonstrated variable malformation of the septum pellucidum, chiasma and nervus opticus or the pituitary gland, respectively. 相似文献
105.
Daniela S Pontes Fernanda A Dorella Luciana A Ribeiro Anderson Miyoshi Yves Le Loir Alexandra Gruss Sérgio C Oliveira Philippe Langella Vasco Azevedo 《Journal of drug targeting》2003,11(8-10):489-493
The Brucella abortus ribosomal protein L7/L12 is an immunodominant antigen and an interesting candidate for the development of oral live vaccines against brucellosis. Here, a recombinant Lactococcus lactis strain producing L7/L12 under the control of nisin inducible promoter was orally administered to BALB/c mice. Significant levels of anti-L7/L12 specific IgA detected in feces revealed an induced local humoral immune response. However, serum analysis did not reveal any anti-L7/L12 antibodies suggesting the absence of a systemic response. Nevertheless, the vaccinated mice showed a partial protective immunity against B. abortus virulent strain (S2308) challenged by intraperitoneal inoculation. 相似文献
106.
Michele Milella Daniela Trisciuoglio Tiziana Bruno Ludovica Ciuffreda Marcella Mottolese Anna Cianciulli Francesco Cognetti Uwe Zangemeister-Wittke Donatella Del Bufalo Gabriella Zupi 《Clinical cancer research》2004,10(22):7747-7756
PURPOSE: To investigate the possible existence of an antiapoptotic cross-talk between HER-2 and antiapoptotic Bcl-2 family members. EXPERIMENTAL DESIGN: Bcl-2 and Bcl-XL expression and apoptosis induction were analyzed in HER-2 gene-amplified (BT474) and nonamplified (ZR 75-1) breast cancer cell lines exposed to trastuzumab, alone or in combination with either Bcl-2/Bcl-XL bispecific antisense oligonucleotides (AS-4625) or the small-molecule Bcl-2 antagonist HA14-1. RESULTS: In addition to HER-2 and epidermal growth factor receptor, trastuzumab down-regulated Bcl-2, but not Bcl-XL, protein, and mRNA expression in BT474 cells. Interestingly, trastuzumab-induced down-regulation of HER-2 and Bcl-2 was also observed in three of five and two of three breast cancer patients undergoing trastuzumab treatment, respectively. Despite Bcl-2 down-regulation, however, trastuzumab only marginally increased the rate of apoptosis (7.3 +/- 3.5%). We therefore investigated whether a combination of AS-4625 and trastuzumab might increase proapoptotic efficiency. AS-4625 treatment of BT474 cells decreased both Bcl-2 and Bcl-XL expression, resulting in a 21 +/- 7% net apoptosis induction; the combination of AS-4625 followed by trastuzumab resulted in a significantly stronger induction of apoptosis (37 +/- 6%, P <0.01) that was not observed with the reverse treatment sequence (trastuzumab followed by AS-4625). Similar results were obtained with the Bcl-2 antagonist HA14-1; indeed, exposure of BT474 cells to HA14-1 followed by trastuzumab resulted in a striking proapoptotic synergism (combination index=0.58 +/- 0.18), as assessed by isobologram analysis. CONCLUSIONS: Altogether our findings suggest that combined targeting of HER-2 and Bcl-2 may represent a novel, rational approach to more effective breast cancer therapy. 相似文献
107.
Heidi Fiegl Conny Gattringer Andreas Widschwendter Alois Schneitter Angela Ramoni Daniela Sarlay Inge Gaugg Georg Goebel Hannes M Müller Elisabeth Mueller-Holzner Christian Marth Martin Widschwendter 《Cancer epidemiology, biomarkers & prevention》2004,13(5):882-888
This proof of principle study aimed to define a new and simple strategy for detection of endometrial cancer using epigenetic markers. We investigated DNA isolated from vaginal secretion collected from tampon for aberrant methylation of five genes (CDH13, HSPA2, MLH1, RASSF1A, and SOCS2) using MethyLight in 15 patients with endometrial cancer and 109 patients without endometrial cancer. All endometrial cancer patients revealed three or more methylated genes, whereas 91% (99 of 109) of the patients without endometrial cancer had no or fewer than three genes methylated in their vaginal secretion. The methods developed in this study provide the basis for a prospective clinical trial to screen asymptomatic women who are at high risk for endometrial cancer. 相似文献
108.
Valeria Masciullo Tommaso Susini Alessandra Zamparelli Alessandro Bovicelli Corrado Minimo Daniela Massi Gianluigi Taddei Nicola Maggiano Pierandrea De Iaco Marcello Ceccaroni Luciano Bovicelli Gianni Amunni Salvatore Mancuso Giovanni Scambia Antonio Giordano 《Clinical cancer research》2003,9(14):5332-5338
PURPOSE: p27(Kip1) is a member of the Cip1/Kip1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. Low levels of p27 are associated with poor prognosis in a variety of gynecological tumors, including breast, ovarian, and cervical carcinomas. The role of p27 in endometrial cancer remains controversial. EXPERIMENTAL DESIGN: In the present study, p27 protein expression was investigated by immunohistochemistry in a series of 217 endometrial adenocarcinomas and, where present, in synchronous normal endometrium, simple and complex hyperplasia (with or without atypia), and cystic atrophy. The relationship between p27 expression and clinical outcome was also evaluated. RESULTS: Immunohistochemical analysis revealed a significant loss of p27 expression from normal (33%) through hyperplastic endometrium (50%) to endometrial adenocarcinomas (71%; P = 0.001). In addition to nuclear staining, cytoplasmic localization of p27 was noted in 193 (91%) of 217 specimens examined. When the clinical outcome of the patients was evaluated in relation to p27 status, we found no significant correlation between the presence of p27 staining and clinicopathological parameters or survival. CONCLUSIONS: These data indicate that p27 expression could progressively decrease from normal endometrium through hyperplastic endometrium to invasive endometrial carcinomas, suggesting that loss of this tumor suppressor may represent a novel and distinct molecular alteration involved in estrogen-related endometrial adenocarcinomas (type I). Despite the suggested role of the p27 protein in determining the prognosis of several human tumors, it was not found to be a predictor of clinical outcome in this large group of patients with endometrial cancer. 相似文献
109.
110.
Expression and activity of CYP2E1 in circulating lymphocytes are not altered in diabetic individuals
Laura Pucci Vera Chirulli Sandra Marini Daniela Lucchesi Giuseppe Penno Pier Giovanni Gervasi Stefano Del Prato Vincenzo Longo 《Pharmacological research》2005,51(6):561-565
Cytochrome P4502E1 (CYP2E1) plays an important role in ROS production thus favouring accelerated membrane lipid peroxidation. This isoform is strongly expressed in the liver but it can be also found in lymphocytes. As such, lymphocyte may provide a non-invasive accessible pool for screening CYP2E1 expression in man. We have, therefore, analysed CYP2E1 expression and activity in lymphocyte microsomes from 12 healthy controls, 11 type 1 and 12 type 2 diabetic subjects by using Western blot and enzymatic activities. Immunoblotting did not show difference among CYP2E1 protein bands in controls, type 1 and type 2 diabetics. To assess CYP2E1 activity we used the 7-ethoxy-4-trifluoromethylcoumarin (7-EFC), as a fluorescent substrate. The rate of deethylation of 7-EFC from controls did not differ from type 1 and type 2 diabetic subjects. The lack of any difference in CYP2E1 activity also was confirmed by the NADPH-dependent microsomal lipid peroxidation CCL4-induced assay showing similar peroxidation rates among controls and diabetic subjects. The results show that CYP2E1 expression/activity in lymphocytes is not enhanced in diabetes. 相似文献