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Biomedical subjects

A Giuliani

Publications and source records attributed to A Giuliani.

At least 145 records · Page 8Linked to original sources
PubMed1992

Spatial memory in aged rats: population heterogeneity and effect of levocarnitine acetyl.

The existence in a population of aging rats of classes that display a different performance in the Morris water-maze test was investigated by cluster analysis procedure. These classes identified at 18 months of age showed a different response to levocarnitine acetyl and had a different behavioral profile when tested at 25 months of age. These findings demonstrate the need for an alternative interpretation of variability in animal populations as measured by the standard statistical analyses. The data analysis strategy we propose here will allow for the use of variability as a useful source of information.

Acetylcarnitine↗
PubMed1992

Simultaneous evaluation of genotoxicity data from different sources: a multivariate statistical approach.

A great deal of information on short-term mutagenicity assays presently exists, having been generated through individual as well as large comparative programs. The comparative programs have often examined the same tests, but with different sets of chemicals; this then gives rise to the problem of how to identify the information which is common to the different data bases, i.e., the general properties of the assays. This paper continues previous analyses of this subject, and describes a general approach by which different and heterogeneous data bases can be compared to each other. The results relative to 4 assays (Salmonella typhimurium gene mutation, mouse lymphoma L5178Y cell gene mutation, chromosomal aberrations in CHO cells, and SCEs in CHO cells) in 4 different data bases were studied. Factor analysis was used to model the different pieces of information. The analysis demonstrated a concordance between the indications of the U.S. National Toxicology Program and the International Program for the Evaluation of Short-Term Tests for Carcinogens, whereas the results of Gene-Tox and the International Program for Chemical Safety turned out to be biased, to different degrees, by their specific aims and characteristics. Moreover, the general properties--independent of the specific data bases--of the 4 assays were highlighted, and the similarities between the performances of the assays were given a quantitative measure.

Animals↗
PubMed1992

Active avoidance learning in old rats chronically treated with levocarnitine acetyl.

The aging laboratory animal is recognized as a suitable experimental model for the investigation on drugs potentially able to retard the age-dependent decline in cognitive functions. There is robust evidence that levocarnitine acetyl (ALCAR), the acetyl derivative of carnitine, when administered chronically, prevents some age-related deficits of the central nervous system, mainly at the hippocampal level. On the basis of this evidence and because learning of active avoidance was demonstrated to become impaired with age, we decided to investigate the effect of ALCAR in rats. For statistical evaluation of results, the Cluster Analysis technique was chosen. This procedure pointed out the great heterogeneity of the old population and allowed the classification of the animals into homogeneous groups according to their response pattern. The effect of ALCAR was evident in the higher number of treated old animals yielding escape responses, indicating that ALCAR can preserve, at least partially, learning and memory from the natural decay occurring with age.

Acetylcarnitine↗
PubMed1992

Electrophilicity as measured by Ke: molecular determinants, relationship with other physical-chemical and quantum mechanical parameters, and ability to predict rodent carcinogenicity.

This paper analyzes electrophilicity data as measured by the Ke system for 205 chemicals including both rodent carcinogens and non-carcinogens. Multivariate statistical methods were used. The analysis identified atoms and substructures contributing to electrophilicity, and permitted to establish a theoretical method by which the Ke value (electrophilicity) of chemicals can be easily estimated. In a subset of chemicals, the Ke parameter was compared with other physical-chemical and quantum mechanical properties: Ke appeared to be mostly correlated with the energy of the lowest unoccupied molecular orbital and with the absolute electronegativity. The role of Ke in structure-activity studies was also investigated; in particular, a comparative analysis of the performance of Ke, Salmonella typhimurium and Ashby's structural alerts in predicting carcinogenicity was carried out. The Ke system performed better than the other systems. However, because of the many different mechanisms underlying carcinogenesis, the Ke system cannot predict the potential carcinogenicity of all kinds of chemicals. It is concluded that the main role of Ke in risk assessment consists in producing a probabilistic estimate of the rodent carcinogenicity of the chemicals: e.g. a chemical with Ke higher than 3.0 x 10(12) M-1S-1 has nearly 80% probability of being a carcinogen. Such a probability estimate can be used to rank the chemicals in a priority scale for subsequent and more detailed studies, either theoretical or experimental. In view of this, the role of our method for estimating Ke is particularly important: it gives rapidly and at no cost a chemical classification for risk assessment and priority setting.

Animals↗
PubMed1992

[Biliary tract surgery in patients of 70 and older: an assessment of our experience with 100 consecutive cases].

A series of 100 consecutive patients aged 70 years and older having biliary tract lithiasis observed over a 19-year period (1970-1989) at the 1st Surgical Department of the University of Rome was analyzed in an effort to define morbidity and mortality. Eighty-eight patients underwent surgical treatment. Three patients died postoperatively (3.4%); 12 patients had local and 13 general complications. The highest incidence of complications occurred in patients with associated diseases and bacteriobilia. A long-lasting symptomatology involved a more frequent exploration of the common bile duct. Morbidity and mortality were not significantly related to the type of surgical procedure performed. Elective biliary tract surgery is a safe procedure even in aged patients.

Age Factors↗
PubMed1991

A 33 kDa protein band is enhanced during long-term adaptation of EUE cells to a hypertonic medium.

A cell line derived from human embryonic epithelium (EUE cells) shows an enhanced expression of a 33 kDa protein when adapted to grow in a hypertonic medium containing 0.246 M NaCl (1.8 x the isotonic concentration). The maximum amount of this protein, followed by SDS-PAGE electrophoresis, was found after 4 days of adaptation; thereafter, the protein band remained fairly constant up to 30 days. When the cells were transferred back to a medium containing 0.137 M NaCl (isotonic medium), the protein pattern reverted to that of control cells. This protein is mainly localized in the cytosol, although a small part is associated with the 150,000 g pellet and needs detergents to be extracted. The molecular weight and the cellular location suggest a possible analogy with the so-called amphitropic proteins, that are known to interact with both the epidermal growth factor receptor and hydrophobic structures, such as the membrane phospholipids and the cytoskeletal components.

Adaptation, Physiological↗
PubMed1991

A new monoclonal antibody to an age sensitive band 3 transmembrane segment.

The appearance of band 3 structural modifications related to aging could be evidenced by means of monoclonal antibodies against senescence antigen. Hence in the attempt to provide an immunological marker of erythrocyte aging, we raised a monoclonal antibody against native band 3 (B6 MoAb), which seems to detect differences in the band 3 molecule from erythrocytes of different ages separated by density gradient. Densitometric evaluation of immunoblotting patterns indicates that the in vivo aging is associated with band 3 monomer degradation. The Percoll separated fractions show a significant increase of those proteolytic fragments that bind the B6 antibody. Finally, protease digestions of unsealed membrane ghosts have been performed to test the binding site of the B6 antibody on the band 3 molecule. The data show that the B6 antibody binds a 19 KDa chymotryptic-tryptic fragment which corresponds to a segment of the looped membrane domain whose steric structure appears to be sensitive to age.

Animals↗
PubMed1991

Sulphated glycosaminoglycans expression in the basement membranes of colorectal adenocarcinomas. Preliminary study: correlation with histological grading.

The expression of sulphated glycosaminoglycans was studied at the ultrastructural level by the high iron diamine technique in the basement membranes of 26 colorectal adenocarcinomas (10 well-differentiated, 7 moderately-differentiated, 9 poorly-differentiated). Sulphated glycosaminoglycan expression was highly variable. It was scored as regular (5 cases), slightly irregular (6 cases), highly irregular (15 cases). In general, poor histological differentiation could be correlated with absent or highly irregular expression. However, in a limited number of cases, severe alterations of basement membranes were also present in well-differentiated (2 cases) and moderately-differentiated (4 cases) tumours. Such a variability shows up a heterogeneity which is not revealed by histological grading.

Adenocarcinoma↗
PubMed1991

What indication is common to different genotoxicity data bases?

This paper studies the relationships among 4 in vitro assays: Salmonella mutation (STY), mouse lymphoma L5178Y cell mutation (MLY), chromosomal aberrations in CHO cells (CHA), and sister-chromatid exchanges in CHO cells (SCE), in 3 different data bases: U.S. National Toxicology Program (NTP), International Program for the Evaluation of Short-Term Tests for Carcinogens (IPESTTC), and International Program on Chemical Safety (IPCS). The analysis is performed by modeling each data base with factor analysis. With this tool, it has been possible to separate the different elements (or components) which play a role in each data base. It has also been possible to demonstrate that--together with some specificities of the data bases--there is a common effect which is independent of the data bases, and which typically represents the 'true' relationships among the assays. This element explains 69% of the information contained in NTP, 50% of that of IPESTTC, and 30% of that of IPCS. This common evidence indicates that the responses of STY and CHA to the 'universe' of chemicals are relatively similar, although STY is a bacterial mutation system and CHA is a mammalian cell test for chromosomal damage. The other similarity apparent from this analysis is the one between MLY (mutation in mouse cells) and SCE (cytogenetic evidence in hamster cells). The implication of this result is 2-fold. On the one hand, it is extremely reassuring that the 3 most important comparative studies agree and show common evidence, and this can be recognized rationally. On the other hand, this evidence implies that the scientists involved in mutagenicity research must face the task of exploring and explaining such relationships.

Animals↗
PubMed1991

Membrane alterations in G6PD- and PK-deficient erythrocytes exposed to oxidizing agents.

After in vitro treatment of normal, glucose-6-phosphate dehydrogenase-deficient or pyruvate kinase-deficient human erythrocytes with three different oxidizing agents, the extent of lipid peroxidative degradation and the alterations of membrane proteins were evaluated. Exposure to tert-butylhydroperoxide induced, most markedly in G6PD- and PK-deficient erythrocytes, a reduction of protein bands 1, 2, 2.1, 3, 4.1, 4.2, and 5, with the appearance of high-molecular-weight aggregates and of "new" polypeptide components in the 29- to 23-kDa region and with a marked increase of membrane-bound globin. Malonyldialdehyde production was highest in G6PD-deficient cells and relatively low in PK-deficient ones. Methylene blue, which had similar but less relevant effects on lipid peroxidation, in G6PD-deficient erythrocytes caused a conspicuous appearance of high-molecular-weight aggregates and a simultaneous relevant decrease of bands 1 and 2 and of membrane-bound globin; it brought about an almost opposite effect in PK-deficient red cells. Acetylphenylhydrazine, which under our conditions appeared the mildest agent, failed, in normal and PK-deficient erythrocytes, to increase malonyldialdehyde production or to alter membrane proteins, whereas it caused, in G6PD-deficient cells, a slight decrease of bands 1 and 2, a more pronounced decrease of band 3, and a marked increase of bands 4.5 and 4.9.

Erythrocyte Membrane↗
PubMed1991

Mathematical models for exploring different aspects of genotoxicity and carcinogenicity databases.

One great obstacle to understanding and using the information contained in the genotoxicity and carcinogenicity databases is the very size of such databases. Their vastness makes them difficult to read; this leads to inadequate exploitation of the information, which becomes costly in terms of time, labor, and money. In its search for adequate approaches to the problem, the scientific community has, curiously, almost entirely neglected an existent series of very powerful methods of data analysis: the multivariate data analysis techniques. These methods were specifically designed for exploring large data sets. This paper presents the multivariate techniques and reports a number of applications to genotoxicity problems. These studies show how biology and mathematical modeling can be combined and how successful this combination is.

Animals↗
PubMed1991

Role of levamisole as immunomodulant in mouse lymphoma model.

Levamisole (LMS) has been considered an immunorestorative agent capable of enhancing host's antitumor immune responses. Clinical studies showed that LMS plays a significant role in adjuvant chemotherapy of colorectal cancer. Therefore studies were performed to test whether LMS would be able to restore graft responsiveness in mice with drug-dependent, age-dependent or virus-dependent immunodeficiency. The results show that LMS has little or no influence on the limited antitumor effects of Dacarbazine or Ara-C in mice bearing allogeneic leukemias (i.e. in a host-tumor model in which immuno-chemotherapy synergism occurs with less immunodepressive anticancer drugs). Moreover LMS does not alleviate allograft response inhibition produced by high-dose Dacarbazine or by a mouse RNA virus. However the agent restored graft responsiveness in aged animals. The limited immunoenhancing effects of LMS, as detected in the present study, suggest that the clinical efficacy of the agent could be due to mechanisms not entirely related to its immunopharmacological properties.

Animals↗
PubMed1991

Increased osmiophilia of glycosaminoglycan-like structures after fixation with cetylpyridinium chloride in human colonic mucosa.

The effects on tissue ultrastructural appearance of fixation with cetylpyridinium chloride (CPC)-additioned formaldehyde were studied at the ultrastructural level in human colonic mucosa. We found that CPC did not impair tissue morphology and induced a remarkable osmiophilia in glycosamino-glycan-like structures, which did not require further staining.

Cetylpyridinium↗
PubMed1990

Hydrolysis of fucosyl-GM1 ganglioside by purified pellet-associated human brain and human liver alpha-L-fucosidases without activator proteins or detergents.

Pellet-associated human brain alpha-L-fucosidase was solubilized with 0.5% (w/v) Triton X-100 and purified by affinity chromatography on agarose-6-aminohexanoyl-fucosamine resin. The procedure resulted in a 290,000-fold purification, a 58% yield and a final specific activity of 11,500 nmol/min per mg of protein. Isoelectric focusing indicated that all six major isoforms (with pI values between 4.1 and 5.3) present in crude brain pellet preparations were purified by the affinity technique. SDS/PAGE indicated the presence of one subunit (54 kDa) and a minor protein band at 67 kDa, which presumably is a contaminant since it was not immunoreactive on Western blotting. The pH optimum of the brain enzyme and its apparent Km for the synthetic substrate 4-methylumbelliferyl alpha-L-fucopyranoside were 5.5 and 0.07 mM respectively. Pellet-associated human brain and liver alpha-L-fucosidases were both capable of hydrolysing fucosyl-GM1 ganglioside without activator proteins or detergents. Linear hydrolysis rates were found only for short incubation times (1-5 min). Optimal enzymic activity at 37 degrees C was found at pH 3.4 for both alpha-L-fucosidases, with no activity at pH values above 4.0.

Blotting, Western↗
PubMed1990

Association to HeLa cells and surface behavior of exogenous gangliosides studied with a fluorescent derivative of GM1.

Cultured HeLa cells were incubated with pyrene-GM1/3H-radiolabeled GM1 ganglioside (1:4 M/M) mixtures for various times. The process of association of pyrene-GM1 with cells was qualitatively and quantitatively the same as that of 3H-GM1. The pyrene-GM1 and 3H-GM1 proportions in the various forms of association with cells were similar to that of the starting ganglioside mixture. After 2-h incubation, the association of ganglioside with cells was well established whereas almost no metabolic processing had occurred. During a 24-h incubation, pyrene- and 3H-GM1 underwent similar metabolic processing and gave rise to catabolic (GM2 and GM3) and anabolic (GD1a) derivatives. Fluorescence spectroscopy experiments carried out with the excimer formation technique on subcellular fractions containing plasma membranes showed that exogenous ganglioside was, in part, associated with the cells in a micellar form removable by trypsin treatment, and in part inserted in a seemingly molecular dispersion. Addition of Ca2+ salts caused aggregation of the ganglioside, as indicated by the increase of the excimer:monomer fluorescence ratio. The phenomenon was Ca2+ concentration dependent (maximum at 10 mM), and subsequent addition of EDTA had no effect. The saccharide portion of exogenously incorporated pyrene-GM1 was available to interact with external ligands, as shown by its ability to bind cholera toxin whose addition reduced the collision rate among the ganglioside lipid moieties.

Calcium↗