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Biomedical subjects

A Giuliani

Publications and source records attributed to A Giuliani.

At least 217 records · Page 12Linked to original sources

DNA repair induction by cytostatic drugs in proliferating and quiescent MRC-5 cells.

The repair of DNA damage is closely related to cell cycle, in terms of both modulation of repairing ability throughout the cell cycle and perturbations in replication. We have studied the induction of Unscheduled DNA Synthesis (UDS) in human fibroblasts (MRC-5) by some chemotherapeutic agents, selected for their different mechanisms of action. To take into account the interaction between repair and replication systems, the experiments were performed in both proliferating and quiescent cultures; semiconservative DNA synthesis inhibition was examined by microphotometric measurements in the same autoradiographic preparations used for UDS analysis. Vincristine, methotrexate and 6-thioguanine induced no UDS. Adriamycin, actinomycin D, and, to a lesser extent, cyclophosphamide and thiotepa gave positive results only in proliferating cultures, whereas bleomycin was an effective inducer of UDS in quiescent cells, with weak UDS levels in proliferating ones. In all these cases, the combined analysis of UDS and semiconservative DNA synthesis inhibition proved to be of value in the assessment of interaction between drugs and DNA in proliferating cultures. The results of our experiments emphasize the importance of the cycling conditions in the cellular response to DNA damage.

Antineoplastic Agents↗

Polar lipids extraction from rat primary lysosomes and their possible role in regulating lysosomal hydrolases.

The polar lipids in primary lysosomes prepared from rat liver were extracted and evaluated by qualitative and quantitative procedures. Phospholipid phosphorus ranges between 1.50 and 2.6 micrograms/mg protein and sulfolipids varied from 12 to 60 micrometer/mg protein. The TLD of the organic phase have nine lipid fractions. Glycolipids were also present: GM1, GM3 and GD1a gangliosides could be separated by TLC. Sialic acid was about 0.24 micrograms/mg protein. The cytochemical interest of these components lies not only in the chemical composition of lysosomal structures, but also in the regulatory mechanism due to some of them, such as sulfolipids, which are likely to be involved in inactivating lysosomal enzymes by cross-inhibition.

Animals↗

Structural or functional heterogeneity of normal human serum albumin, allo albumin, bisalbumin.

The present paper reports a comparative isoelectric focusing study of electrophoretically normal and abnormal albumins. All the albumins were purified by two different techniques (cellulose acetate electrophoresis and preparative slab isoelectric focusing), and submitted to analytical isoelectric focusing before and after incubation with either metabolites or drugs. Isoelectric focusing patterns show general heterogeneity, both in normal and in any of the observed alloalbumins. The heterogeneity is increased in bisalbumins (drug or metabolite induced), showing the same electrophoretic pattern as alloalbumins. The differences are related to the amount of the ligands. The results agree with the hypothesis that the heterogeneity depends on the structure and the carrier function of albumin.

Albumins↗

Hemoglobin bologna (alpha 2 beta 2 61 (E5) lys replaced by met). An abnormal human hemoglobin with low oxygen affinity.

An abnormal human hemoglobin was found in association with beta-thalassemia in a hemolysate from an 11-year-old healthy child living in Bologna (northern Italy). Structural studies demonstrated a previously unreported amino acid substitution, beta 61 (E5) Lys replaced by Met (this is an external residue). The new variant has been named Hb Bologna, and is characterized by a reduced oxygen affinity. Family studies indicated that the variant had been inherited from the father, a 41-year-old male of Southern Italian origin. Also, a brother of the propositus was found to be an abnormal Hb carrier.

Adult↗

beta Thalassemia associated with increased HB F production. Evidence for the existence of a heterocellular hereditary persistence of fetal hemoglobin (HPFH) determinant linked to beta thalassemia in a southern Italian population.

A family has been observed in which a beta thalassemia determinant is inherited over three generations together with high Hb F level (8-12%) and increased number of fetal-hemoglobin-containing-cells (F-cells). The values of red cell indices and globin chain synthesis ratios, yet typical of beta thalassemia, were significantly shifted to the normal values when compared with those of typical beta thalassemia heterozygotes belonging to the same family group. The occurrence in these individuals of a heterocellular hereditary persistence of fetal hemoglobin (HPFH) determinant and its linkage relationship with the beta thalassemia is discussed. In the third generation two adult individuals were beta thalassemia homozygotes having inherited a beta thalassemia determinant from one parent and a beta thalassemia together with the HPFH determinant from the other. They showed an extremely mild clinical condition, and 11-12 g/dl of mainly Hb F without having ever required blood transfusions. Virtually all the red cells were F-cells in both subjects. The importance of the coexistence of HPFH determinants capable of increasing the size of the F-cell population in patients affected by homozygous thalassemia is discussed, considering the sensible benefit which derives from enhanced Hb F production in this syndrome.

Adolescent↗

Conventional haemodialysis and ultrafiltration: effects on erythrocyte 2,3-diphosphoglycerate and oxygen affinity in patients with uraemia.

1. The relationship between erythrocyte 2,3-diphosphoglycerate (2,3-DPG) and changes in blood pH and in oxygen affinity were studied in six patients treated with two dialysis techniques: conventional haemodialysis and ultrafiltration followed by conventional haemodialysis. 2. The decrease in erythrocyte 2,3-diphosphoglycerate and increase in pH after conventional haemodialysis may significantly increase the affinity of haemoglobin for oxygen and consequently result in inadequate oxygenation of tissue. 3. Ultrafiltration followed by conventional haemodialysis, on the contrary, is more beneficial for oxygenation of tissue and post-dialysis symptoms may be reduced.

Adolescent↗

Hemoglobin Legnano (alpha 2 141 (HC3) Arg leads to Leu beta2) a new high oxygen affinity variant. Functional and structural studies.

Hb Legnano (alpha 2 141 (HC3) Arg leads to Leu beta 2) is an abnormal hemoglobin, for which preliminary structural and functional studies demonstrated an amino acid substitution (Arg leads to Leu) in the alpha-C-terminus. This substitution modifies the functional properties observed in whole blood as well as in red blood cells, as reported in this paper. On the basis of its pI, previously determined by analytical isoelectric focusing (IEF), Hb Legnano was purified on a preparative IEF slab. The purified fraction was subjected to functional ultracentrifugal studies under various conditions of pH and salt concentration. The findings are compared with those for Hb Suresnes (alpha 2 141 (HC3) Arg leads His beta2) and Hb-CPB, a normal hemoglobin in which the C-terminal alpha 141 Arg has been cleaved by carboxypeptidase B. Hb Legnano, like the other hemoglobins considered, shows an increased P50, a decreased Hill's "n" values and a decreased Bohr effect that are partially restored in presence of organic phosphates. The presence of inorganic ions decreases the Bohr effect and enhances the dissociation into dimers, as observed in Hb-CPB. The dissociation of hemoglobin in carboxy form in ultracentrifugal studies and the different slope of Hill's "n" value as a function of pH are presumably due to presence of Leu, which probably modifies the stereochemistry of the variant.

Amino Acids↗

Expression of thymidine kinase activity in hybrids between human leukemic cells and a TK-mouse cell line.

A series of actively proliferating clones have been isolated after PEG-induced fusion of a thymidine kinase deficient murine line and white blood cells from two leukemic patients. Their hybrid nature was proved both cytologically and biochemically. All the hybrids tested showed levels of TK activity significantly higher than the TK- mouse parental cell line and comparable to those exhibited by replicating TK+ cells.

Animals↗

Thin-layer isoelectric focusing of hemoglobin variants: screening and determination of isoelectric points.

The high resolving power of thin-layer isoelectric focusing was applied for screening some hemoglobin variants classified on the basis of their electrophoretic mobility in: electrophoretically slow variants (as Hb A2), electrophoretically slow variants (as Hb S), electrophorectically fast variants (Hbs type J). An analysis of the variant compounds has been performed, and the corresponding pI values were determined in whole hemolysate.

Genetic Variation↗

Predicting carcinogenicity with short-term tests: biological models and operational approaches.

This paper illustrates the basic biological models that have had an influence on the development and deployment of short-term assays for carcinogens. A tentative description of such a conceptual framework is provided with the use of methods for the quantitative analysis of information. This picture is contrasted with the results of a series of statistical mathematical analyses carried out on real genotoxicity data bases. The resulting evidence indicates that the biological models derived from basic laboratory research are not adequate or sufficient to interpret the operational performances of short-term assays. Obviously these models are of great importance, but, this observed discrepancy suggests the need for articulated approaches, with particular emphasis on analytical tools able to interpret the complexity of these systems. In particular, the multivariate data analysis methods are indicated as suitable for the description of large and complex bodies of data, and the identification of typologies and regularities. A number of applications of such methods are also presented. The conclusion is that biological models and operational approaches have to interact on the same level. The operational approach should indicate whether the conceptual framework of the experimenter is adequate to describe the experimental situation and possibly point to new relationships and trends, as well as to practical solutions.

Animals↗

Spatial learning and memory in the radial maze: a longitudinal study in rats from 4 to 25 months of age.

This longitudinal study was designed to investigate whether previous experience may influence performances and strategies of rats tested in the radial maze without external cues when aged 4, 13, and 25 months. Their performances and strategies were compared with those of another group of rats tested only when aged 25 months. Expert old animals showed a good retention of previous experiences, whereas age-matched nonexpert animals exhibited some acquisition deficits. On the contrary, in the course of aging, the animals kept modifying their strategies independently of experience. In summary, we can conclude that previous experience is likely to influence performances of the aged rat but not the strategies adopted which are strictly age-dependent and independent of acquired experience.

Aging↗