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Biomedical subjects

A Giuliani

Publications and source records attributed to A Giuliani.

At least 127 records · Page 7Linked to original sources
PubMed1994

Quantitative structure-activity relationship (QSAR) studies in genetic toxicology: mathematical models and the "biological activity" term of the relationship.

At first sight, the QSAR issue might appear to be a mere pattern recognition problem; however, a purely "surface" approach to QSAR as a pattern recognition problem, not involving the profound plausibility of the solutions, has often been demonstrated to be devoid of scientific value and of predictive strength. The requirement for such a lateral validation should imply the recognition of the basic differences between the two terms of the QSAR issue: biology and chemistry. In particular, the difficulty to derive strong quantitative theories for the biological aspect of QSAR procedures should be taken into serious consideration. Within this conceptual framework, this paper examines the different families of mathematical models (classical regression, multivariate methods, neural networks) used in the QSAR research.

Mathematics↗
PubMed1994

QSAR models for both mutagenic potency and activity: application to nitroarenes and aromatic amines.

We studied the molecular determinants that discriminate between mutagenic and inactive compounds for: a) aromatic and heteroaromatic amines; b) nitroarenes. Mutagenic activity (data from literature) had been previously assessed in Salmonella typhimurium and Escherichia coli (SOS repair). The Quantitative Structure-Activity Relationships (QSAR) found were compared with those obtained in the laboratory of Professor C. Hansch for the mutagenic potency of the same compounds. It appears that there is a dramatic difference between the QSARs for potency, and those for yes/no activity: hydrophobicity played a major role in determining the potency of the active compounds, whereas mainly electronic factors differentiated the actives from the inactives. The electronic factors were those expected on the basis of the hypothesized metabolic pathways of the chemicals. Our interpretation is that the electronic factors (together with size/shape, possibly) determine the minimum requirement for the chemicals to be metabolized, whereas the hydrophobicity determines the extent of activity of chemicals that can be metabolized (actives). Moreover, the different QSARs found for the Salmonella strains TA98 and TA100 were discussed in the light of recent progress in the understanding of the molecular mechanisms of mutagenicity in these organisms. It is concluded that the nonlinear relationship observed for these chemicals between the two types of QSAR should be taken into account both when planning QSAR studies, and when using mutagenicity data for risk assessment.

Amines↗
PubMed1994

Effects of concomitant nicotinic and muscarinic blockade on spatial memory disturbance in rats are purely additive: evidence from the Morris water task.

This study reexamined the role played by a concurrent manipulation of nicotinic and muscarinic acetylcholine (ACh) receptors on performance of rats in the Morris water maze. A series of experiments was performed to test decreasing doses of scopolamine, a muscarinic ACh blocker, given concurrently with a fixed dose level of mecamylamine, a nicotinic ACh blocker, down to a subthreshold combination. Both substances were also tested separately. Data were analyzed to distinguish between a summative and a greater than additive (synergistic) effect of the two blocking agents. Our results fully support the important role played by ACh systems on cognitive functions and also show the substantial functional independence of the two ACh receptors in regulating spatial learning processes. In fact, data analysis did not reveal any significant interaction between the two ACh receptor blockers other than their additive effect: the hypothesis of a reciprocal modulation between the two ACh receptors, raised by some authors, cannot be supported for spatial learning mechanisms, at least with regard to the Morris water maze paradigm.

Animals↗
PubMed1994

Nonparametric scaling: a descriptive index.

A descriptive index (CI) based on the U statistic is presented. The CI permits to quantify the differences between experimental samples taking into account both the location and variability features of the data without any distributional assumption. This index can be useful to build activity scales for series of compounds.

Drug Evaluation↗
PubMed1994

Multivariate analysis of behavioral aging highlights some unexpected features of complex systems organization.

Ten different behavioral tests were performed on a population of young (n = 20) and aged (n = 20) Fischer 344 rats. The relationship structure among these tests was studied by principal component analysis applied both to the entire data set and separately to the two age groups. This analysis proved very useful in highlighting a global index of the rat "behavioral" age based on the entire test set. The analysis effected separately on the two age groups evidenced qualitative differences between them that were linked to the different meaning the same test would assume in rats of different ages. From an overall methodological viewpoint, this work indicates that the correlations among behavioral parameters appear to depend on the observational scale and that the spin-glass model represents an appropriate metaphor to approach the study of the correlations in biological systems.

Aging↗
PubMed1994

Drug-mediated changes in the susceptibility of human lymphoblastoid B cells to NK-mediated cytolysis: studies with a triazene compound.

Previous studies have shown that treatment of leukemia-bearing mice with triazene compounds results in a profound alteration of the immunological properties of leukemic cells. These cells become highly immunogenic and susceptible to natural immunity (NI). Moreover, in a pilot clinical study, dacarbazine was found to suppress bone marrow blasts in patients with acute non-lymphoblastic leukemias. The cytotoxic mechanism involved could be of biochemical and immunological origin as well. Therefore experiments were carried out to test whether triazenes could influence the susceptibility of blast cells to human NI effector lymphocytes (represented, at least in part, by NK cells). The results obtained with target Epstein-Barr virus (EBV)-immortalized B cells and effector cells of different donors, showed that: (a) multiple in vitro treatments of lymphoblastoid cells with methyl-triazene-benzoic acid (MTBA, a triazene compound active in vitro), gave origin to lines that were more resistant than the parental lines to the antitumor effects of MTBA; (b) MTBA-treated lines were more susceptible (37.5% of cases), or less susceptible (31.2% of cases) to NI than parental cells. Effector lymphocytes of various donors recognized different changes in susceptibility to natural killer (NK)-mediated lysis; (c) treatment of parental or MTBA-treated lines with interferon-beta reduced target cell susceptibility to NK-mediated cytolysis, but increased NK activity and lymphoblast chemosensitivity to MTBA.

Antineoplastic Agents↗
PubMed1994

Quantitative modeling and biology: the multivariate approach.

Even though elegant examples of mathematical modeling of biological problems exist, such approaches still remain outside the domain of most biologists. It is proposed that, for a wider and more systematic use of mathematical models in biology, the soft modeling approaches, which are applicable to phenomena with a limited level of definition, should be investigated and preferred. In particular, multivariate data analysis (MDA) is indicated as an important tool toward fulfilling this goal. This paper reviews the general principles of MDA and examines in detail principal component analysis and cluster analysis, which are two of the most important MDA techniques. A number of applications to real biological problems are presented. These examples show how the construction of classifications corresponds to the generation of new knowledge and new concepts, which are hierarchically on a higher level than the initial information. This new form of knowledge is obtained without superimposing a priori theories on the data. It is demonstrated how the MDA can lead to the identification of biological systems; also shown is their ability to describe multiple scale phenomena, a typical feature of biological systems. Moreover, the multivariate analyses provide new descriptors for a given biological system; these descriptors are quantitative, thus allowing the system to be described in a "metric space," where it then becomes possible to use any other mathematical tool.

Animals↗
PubMed1994

In vitro combined effects of a triazene compound and interferon-beta on natural immunity against lymphoblastoid cells: studies at effector and target cell level.

It was shown that Dacarbazine and other triazene compounds render murine leukemias highly immunogenic and susceptible to natural immunity (NI). In addition a pilot clinical study revealed that Dacarbazine can be cytotoxic for bone marrow blasts in patients with acute non-lymphoblastic leukemias through a mechanism that could be, at least in part, of immunological origin. However triazenes depress antigen-dependent responses and NI, whereas interferons, including interferon-beta (IFN), antagonize drug-induced impairment of NI. Therefore the complex interaction between triazenes and IFN on NI effector (i.e. NK) lymphocytes and human target lymphoblastoid cells has been investigated. The results show that: (a) IFN increases NK activity and antagonizes the depressive effects of methyl-triazene-benzoic acid (MTBA, an in vitro active triazene compound) on the NK function; (b) a lymphoblastoid cell line exposed to multiple in vitro treatments with MTBA, shows increased growth rate, augmented chemoresistance to MTBA, and higher susceptibility to NI than parental cells; (c) as expected IFN pretreatment down-regulates the susceptibility of lymphoblastoid cells to NK effectors; (d) however a net "therapeutic gain" was found if the overall influence of MTBA+IFN on target and effector cells is considered.

Antibodies, Monoclonal↗
PubMed1994

[Monitoring of antithrombin III in general surgery].

The authors studied the effects of surgery on hemocoagulation parameters (PT, PTT, PLT, Fibrinogen, AT III). 30 patients, undergoing extrahepatic surgery were observed. Measurements were performed before, during and immediately after procedure, and 24 hs and 48 hs later. Results showed a significant drop of AT III activity (p < 0.05) throughout the surgical procedure with a prompt reversal to normal values right after the end of it. Fibrinogen values continuously increased from the end of surgery (compared to intra-op values) (p < 0.05) up to 48 hs (p < 0.01). PTT values decreased at the end of surgery (p < 0.05) and returned to normal during the following 24 hs. No thromboembolic and hemorrhagic complications were observed during the postoperative phase, with all patients being discharged after surgical resolution of pathologies. In conclusion accurate monitoring of hemocoagulation parameters (especially AT III) seems to be useful in order to prevent thromboembolic and/or hemorrhagic complications during and after surgery.

Adult↗
PubMed1994

The role of surgery in stage IIIa non-small cell lung cancer. Surgery in IIIa NSCLC.

The authors have reviewed the records of 50 consecutive patients resected for stage IIIa non-small cell lung cancer and included in a long-term follow-up study at the 1st Department of Surgery, University of Rome "La Sapienza". Overall survival was 60-20-16.6-16.6% at 1-5-7-10 years with an incidence of recurrence and/or metastasis respectively of 56-80-85.6-85.6%. These percentages were not influenced by the histological type. Tumours with the best prognosis were those classified as T1N2 and T3N0 (7-year survival rate: 33.3 and 29.4% respectively). Tumours with the worst prognosis were those classified as T3N2 with the highest incidence of relapse after 6 months (T3N0 vs T3N2 0.01 < p < 0.025) and no survival after 3 years (T3N0 vs T3N2 0.005 < p < 0.01). Regarding T3 tumours, infiltration of mediastinal pleura or pericardium was a negative prognostic factor implying no survival at 30 months. Involvement of chest wall or parietal pleura showed better survival overall although not statistically significant (10-year survival rate: 37.4 vs 24% respectively).

Carcinoma, Non-Small-Cell Lung↗
PubMed1994

Interlamellar lipid differences between normal and psoriatic stratum corneum.

Intercellular lipids of the stratum corneum are involved in permeability barrier integrity and function. In psoriasis, desquamation and permeability barrier homeostasis are modified; these observations are consistent with an alteration in stratum corneum lipid production. Therefore, in the present study, we determined and compared the total content of the three main intercellular lipids in psoriatic scales and normal human stratum corneum. Our results showed that the relative free fatty acid content decreased remarkably (46%) in psoriatic scales, compared with normal human stratum corneum. This decrease may reflect a general state of emergency of keratinocytes, in which free fatty acids can be employed.

Ceramides↗
PubMed1993

Synthesis and amnesia-reversal activity of a series of 7- and 5-membered 3-acylamino lactams.

A series of 3-(acylamino)-epsilon-caprolactams and 3-(acylamino)-2-pyrrolidinones was synthesized. Some of these compounds reversed at different degrees electroconvulsive shock- and Scopolamine-induced amnesia, using a step-through passive avoidance in mice. Classical nootropic drugs, i.e., Aniracetam, Oxiracetam, and Piracetam, were used as reference compounds. Within the analyses of data performed, we introduced a new parameter, the confrontation index (CI), which is a function of Mann-Whitney's U statistic. The CI permits a common scale of activity of substances to be generated, independently of probabilistic hypotheses, with higher scores representing higher activities. The most active compounds were characterized by the formylamino and [3-(trifluoromethyl)benzoyl]amino groups in the 3-position of the ring. None of the substances assayed showed any effect on spontaneous behavior and neurovegetative system.

Amnesia↗
PubMed1993

Aldose reductase is involved in long-term adaptation of EUE cells to hyperosmotic stress.

Aldose reductase has been shown to be expressed in large amount by human embryonic epithelial cells (EUE) in response to osmotic stress. This conclusion is the result of studies undertaken following the purification to homogeneity of two forms of a 35-kDa protein overexpressed in EUE cells grown in hypertonic saline culture medium as compared to EUE cells grown in isoosmotic medium. Amino-acid composition, molecular weight and partial internal amino-acid sequence showed that the above proteins are two different forms of aldose reductase. These findings were confirmed by the observation that aldose reductase activity increased about 150-fold in adapted cells and returned to basal levels in de-adapted cells.

Adaptation, Physiological↗
PubMed1993

Action of alpha-L-fucoside from Octopus vulgaris hepatopancreas on phospholipid vesicles containing the fucosylated ganglioside FucGM1.

The behaviour of a highly purified alpha-L-fucosidase (E.C. 3.2.1.51) extracted from octopus hepatopancreas was studied with phospholipid vesicles composed of phosphatidylcholine (PC) and phosphatidylserine (PS) containing the fucosylated ganglioside FucGM1, a potential natural substrate of the enzyme. The substrate recognition and hydrolysis take place only with PS/FucGM1 mixtures via an association process of the enzyme with the vesicles at acidic pH; the enzyme rapidly and stably binds to PS vesicles but not to PC vesicles. The data suggest that only the PS-associated enzyme is able to hydrolyse FucGM1 embedded in the same bilayer. The enzyme association with FucGM1/PS vesicles is a prerequisite for ganglioside hydrolysis but is followed by irreversible enzyme inactivation.

Animals↗
PubMed1993

Antioxidant erythrocyte enzyme activities during oral contraception.

Nineteen healthy young women, non-smokers and of normal weight, used a combined oral contraceptive, consisting of 20 micrograms ethinylestradiol and 150 micrograms desogestrel, for 9 cycles and were investigated before starting oral contraceptive use, and during the 3rd, 6th and 9th cycle. In all cases, the antioxidant erythrocyte enzyme activities, superoxide-dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GSH-Px), were determined. Pyruvate-kinase (PK) activity was also considered as a predictable index of the age and constancy of the erythrocyte population. A steady, significant increase in GSH-Px and CAT enzyme activities was found. No significant variations were found in SOD and PK enzyme levels. These findings clearly suggest that the use of combined oral contraceptives leads to an increase in antioxidant defenses. The specific physiological and biochemical mechanisms of this response merit further investigation.

Adolescent↗
PubMed1993

Use of octadecylrhodamine fluorescence dequenching to study vesicular stomatitis virus fusion with human aged red blood cells.

Human erythrocytes were separated into five fractions representing different age groups. In each group phospholipid inside-outside translocation was determined by quantitation of the amino phospholipids phosphatidylserine and phosphatidylethanolamine and their lyso-derivatives by thin layer chromatography. To assess the role of transbilayer phospholipid distribution in the recognition and fusion of vesicular stomatitis virus (VSV) and human aged erythrocytes, we monitored the fusion kinetics using the octadecylrhodamine dequenching assay. Fusion of VSV with each single group of red blood cells (RBC) was not detectable with the youngest cells (F1 group) but increased with RBC aging (F2-F5 groups). The same increase in fusion was observed with microvesicles generated from RBC in which aging was mimicked by incubating the cells with Ca2+ in the presence of the Ca2+ ionophore A23187. Conversion of the aminophospholipids to the trinitrophenyl derivative by reaction with trinitrobenzensulfonate completely inhibits fusion on ghosts in which aging was artificially induced by translocation of aminophospholipids in the outer leaflet (symmetric ghosts). These results indicate that RBC become susceptible to VSV fusion during aging and in all pathology related to the aging process.

Erythrocyte Aging↗
PubMed1992

A monoclonal antibody monitoring band 3 modifications in human red blood cells.

Morphologic and metabolic erythrocyte modifications are thought to be the basis of cell removal from circulating blood. A significant role has been ascribed to the immunological network which may remove aged or misshapen erythrocytes through the binding of specific autoantibodies. Along this line recent observations indicate that a senescence antigen appears in consequence of postsynthetic modifications of band 3, one of the most important erythrocyte membrane proteins, which accounts for many functional activities of the red cells. On this basis, we raised a mouse hybridoma anti-band 3 monoclonal antibody (B6 MoAb) of the IgG2a class which monitors band 3 differences among normal red blood cells separated by Percoll density gradient. These differences are outlined by the decrease of B6 MoAb binding to band 3 monomer, the appearance of an 80-90 kDa new band, lighter than band 3, and the increase of low molecular weight fragments in the 4.5 region. The B6 MoAb appears to be very useful in detecting modifications of band 3 since it bind to a 19 kDa Chy-Try fragment estimated to be sensitive to aging.

Aging↗