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Biomedical subjects

A Giuliani

Publications and source records attributed to A Giuliani.

At least 163 records · Page 9Linked to original sources

Motor neuron disease in a patient with a monoclonal IgMk directed against GM1, GD1b, and high-molecular-weight neural-specific glycoproteins.

In a patient with motor neuron disease and benign IgMk monoclonal gammopathy, the M protein reacted with the glycolipids GM1, GD1b, and asialo GM1 and, by immunoblot, with some high-molecular-weight neural-specific glycoproteins. The main reactive bands had an approximate molecular weight of 250 and 400 kd, were most concentrated in the spinal cord, and were also bound by the lectin peanut agglutinin. The presence of the Ga1(beta 1-3)Ga1NAc epitope on these neural-specific glycoproteins may help to explain the selective neurological impairment of the patient.

Gangliosides↗

Further studies on the gangliosidic nature of the cholinergic-specific antigen, Chol-1.

The antigen designated as Chol-1 beta, detected by an antiserum specific for cholinergic neurons, has been purified to homogeneity from ganglioside mixtures extracted from Torpedo electric organ and pig brain. The final products from the two sources behaved identically in a wide range of tests and gave coincident immunopositive and Ehrlich-positive spots after thin layer chromatography in seven different solvent systems; they were thus considered to be identical and to constitute a single, pure chemical species. Gas-chromatographic analysis revealed the presence of long-chain bases, glucose, galactose, N-acetylgalactosamine, and sialic acid in integral molar ratios of 1:1:2:1:3; the compound's reactivity to cholera toxin after Vibrio cholerae sialidase treatment on thin layer chromatography and the recovery of GM1 as sole product of exhaustive sialidase treatment identified it as a member of the gangliotetrahexosyl series. From the products of partial enzymatic desialylation and treatment with beta-galactosidase and a comparison of the compound's immunoreactivity to anti-Chol-1 antisera with that of other trisialogangliosides of defined molecular structure, we were able to assign a disialosyl residue alpha-Neu5Ac-(2----8)-alpha-Neu5Ac-(2----3)- to the inner galactose, and we suggest GalNAc as a possible site of linkage of the third sialic acid.

Animals↗

Aging and immune response: a multivariate approach.

This study on the immune response was chosen as the experimental milieu for the aging process. Parameters associated with the immune response were measured in rats of different ages, thus providing multivariate conditions within which multidimensional data analysis procedures could be applied. These methods, specifically designed for analyzing complex situations, allowed for the delineation of some structural characteristics of maturity and senescence.

Aging↗

Inhibition of replicative DNA synthesis and induction of DNA repair in human fibroblasts by the intercalating drugs proflavine and 9-aminoacridine.

The induction of unscheduled DNA synthesis (UDS) and the alteration of semiconservative DNA replication by the structurally related intercalating agents proflavine and 9-aminoacridine were studied in MRC-5 human fibroblasts in culture. Autoradiographic determinations of both parameters were carried out simultaneously in the same culture specimens. Proflavine affected DNA synthesis, but did not elicit any UDS. 9-Aminoacridine inhibited DNA synthesis only at the highest concentration and caused UDS to a low but significant extent. These results suggest that the ability to induce UDS is not a general property of the intercalating agents and that the alterations of the DNA structure, typical of the "pure" intercalative process, are not handled by pathways involving unscheduled synthesis.

Aminacrine↗

Changes in the ceramide composition of rat forebrain gangliosides with age.

Five major gangliosides (GM1, GD1a, GD1b, GT1b, and GQ1b) were extracted and isolated by normal-phase HPLC from the forebrain of Sprague-Dawley rats of ages ranging from 3 days to 24 months. Each ganglioside was fractionated by reverse-phase HPLC into the molecular species carrying a single long-chain base moiety. At all ages, the C18:1 and C20:1 long-chain base species predominated, whereas the C18:0 and C20:0 ones represented 1-3% of the total. The C18:1 long-chain base species, predominant at 3 days (91-96%), diminished with age and reached, at 2 years, 73%, 65%, 61%, 59%, and 45% of the total for GD1a, GM1, GT1b, GD1b, and GQ1b, respectively. The content of the C20:1 long-chain base species, low at birth (4-9%), increased with age in all gangliosides and reached, at 2 years, 27-55% of the total. The developmental behavior of the ganglioside species containing the C18:1 long-chain base was characterized by the following: (a) a biphasic profile with a maximum around 15 days for GD1a, the most abundant ganglioside at all ages; (b) an increase until 6 months for GM1; (c) a sharp decrease until 30 days, followed by leveling for GT1b; and (d) a low, constant level for GD1b and GQ1b. All the ganglioside species containing the C20:1 long-chain base showed a constant increase during development, the increase being more marked in the first 30 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Role of vincristine in immunochemotherapy of leukemia in mouse or human models.

Synergistic antitumor effects between Vincristine (VCR) and allograft responses have been found in mice bearing allogeneic retrovirus-induced leukemia. In this model VCR depressed weakly allograft reactivity if given before but not after antigen administration. In a parallel human tumor model in vitro using HTLV-1 induced MT-2 leukemia, additive but not synergistic immuno-chemotherapeutic effects were obtained with allogeneic mononuclear cells (MNC) combined with VCR at 0.1 but not at 1 micrograms/ml. In this case natural immunity (NI) rather than antigen-dependent immunity (ADI) was involved in the combined effects of VCR + MNC. In the in vitro model pretreatment of effector cells with 1 or 0.1 micrograms/ml of VCR depressed natural cell-mediated cytotoxicity (NCMC). However when the drug was added to the effector + target cells during the 4 h cytotoxicity assay, 1 but not 0.1 micrograms/ml of the drug was capable of depressing NCMC function. These results would provide valuable information for developing in vitro immuno-chemotherapy studies in human tumor systems, including those characterized by the presence of tumor-associated oncogenic retroviruses, capable of depressing both NI and ADI functions.

Animals↗

Changes of gene expression during long term adaptation of human EUE cells to a hypertonic medium: electrophoretic protein patterns and DNase I digestion in situ.

The effects of long term (1 to 10 days) growth in a hypertonic medium have been studied in human EUE cells. Following polyacrylamide gel electrophoresis, a change in the protein pattern has been found, with the progressive enhancement, during adaptation, of a 33 kDa band. Experiments of DNA digestion in situ by DNase I showed that chromatin DNA of cells grown in a hypertonic medium is more available to the enzyme cleavage. These findings show that long term hypertonic stress is able to induce a change in gene expression in EUE cells.

Cells, Cultured↗

Ultrastructural immunolocalization of laminin and fibronectin in human large intestinal mucosa.

The ultrastructural expression of laminin and fibronectin was studied in human colonic mucosa with a pre-embedding immunoperoxidase technique. Both antigens were present in epithelial basement membrane. The lamina densa was uniformly and homogeneously immunostained by both fibronectin and laminin, while the lamina rara showed discrete, positive sites occasionally connecting the lamina densa with the epithelial plasma membrane. In the lamina reticularis, fibronectin was diffusely positive, while laminin showed a discontinuous positivity only in the uppermost region in vicinity of the lamina densa. Collagen fibrils were regularly decorated by fibronectin-positive material. Basement membranes in the capillary wall showed a similar pattern of reactivity both with laminin and fibronectin. These results point out that laminin as well as fibronectin are integral components of intestinal mucosa basement membranes.

Basement Membrane↗

Ultrastructure of the absorptive cell glycocalyx in hyperplastic colonic polyps after staining with alcian blue and high iron diamine.

The glycocalyx of absorptive cells in large intestinal hyperplastic polyp was characterized histochemically at the electron microscope level by the use of the Alcian Blue pH 2.5 and high iron diamine techniques with the aim of comparing their ability in preserving the fine reticular network of the structure. Both the reagents stained glycocalyx, indicating the presence of sulphated acidic glycoconjugates. However, they showed different degrees of condensation of the reactive sites. Alcian Blue preserved its filamentous appearance better.

Alcian Blue↗

Maternal adrenalectomy and adult offspring in a conflict situation in the rat.

The effects of the absence of maternal adrenals during pregnancy (P), during lactation (L), during pregnancy and lactation (PL) were studied on pain suppressed behavior (punished drinking test) of the adult offspring in comparison with controls (C). The female L offspring showed a lower responsiveness to the anxiogenic stimulus, as demonstrated by increased water intake, decreased percentage of ineffective licks, and decreased time to perform 300 licks compared to C. The male L behavior was not affected. Reduced growth was not responsible for the reduced anxiogenic reactivity because also both male and female PL offspring had lower weight than C, but did not show any significant effect. Pain threshold in the tail flick test was the same in all types of offspring. Thus, absence of maternal adrenals, specifically during lactation, significantly affects behavior of female offspring. It is discussed whether this is due to the lack of a physiological influence of maternal adrenal hormones on brain ontogenesis (hippocampal glucocorticoid receptors), or on the development of the brain-pituitary-adrenal system during neonatal life of the offspring.

Adrenalectomy↗

Interrelationships among carcinogenicity, mutagenicity, acute toxicity, and chemical structure in a genotoxicity data base.

The interrelationships among carcinogenicity, mutagenicity, acute toxicity (LD50), and a number of molecular descriptors were studied by computerized data analysis methods on the data base generated by the International Program for the Evaluation of Short-Term Tests for Carcinogens (IPESTTC). With the use of statistical regression methods, three main associations were evidenced: (1) the well-known correlation between carcinogenicity and mutagenicity; (2) a correlation between mutagenicity and toxicity (LD50 ip in mice); and (3) a correlation between toxicity and a recently introduced estimator of the free energy of binding of the molecules to biological receptors. As expected on the basis of the large variety of chemical classes represented in the IPESTTC data base, no simple relationship between mutagenicity or carcinogenicity and chemical descriptors was found. To overcome this problem, a new pattern recognition method (REPAD), developed by us for structure-activity studies of noncongeneric chemicals, has been used. This allowed us to highlight a significant difference between the whole patterns of relationships among chemicophysical variables in the two groups of active (mutagenicity and/or carcinogenic) and inactive chemicals. This approach generated a classification rule able to correctly assign about 80% of carcinogens or mutagens.

Carcinogens↗

Comparison of different computerized classification methods for predicting carcinogenicity from short-term test results.

A major obstacle to the use of short-term test results for predicting carcinogenicity is the nonavailability of methods that generate unequivocal estimations of potential carcinogenicity, even in the case of contrasting test results. We compared different mathematical classification methods such as linear discriminant analysis, the K-nearest neighbor rule (KNN), and a new ad hoc classification method called dynamic carcinogenicity assessment (DYCA). The DYCA was developed by us to explicitly reflect the biological results. Through an analysis of a real data base we pointed out the advantages and limitations of these methods. KNN was clearly inferior to the other two algorithms. The novel DYCA approach was more sensitive to carcinogens, whereas linear discriminant analysis proved better for the identification of noncarcinogens.

Carcinogenicity Tests↗

Structure-activity studies of chemical carcinogens: use of an electrophilic reactivity parameter in a new QSAR model.

Electrophilic reactivity data for 142 compounds were obtained from the literature, and were used to establish the contribution of different functional groups and molecular determinants to this property. An equation containing approximately 20 molecular determinants was derived (r = 0.89); this provided a system for estimating the electrophilic reactivity for other compounds on the basis of their molecular structure. The contribution of the estimated electrophilicity to the structure-activity relationship (SAR) studies of carcinogens was tested. In a previous work, we studied a set of 137 carcinogens and non-carcinogens belonging to different chemical classes, and established an SAR on the basis of four physical-chemical descriptors. The mathematical model consisted of a pattern recognition method specifically designed by us for the non linear situations typical of large non congeneric sets of chemicals. The addition of the estimated electrophilicity parameter increased the overall performance of the system (from the previous 85-90% retrospective correct classification). In particular, the estimated electrophilicity remarkably contributed to the identification of carcinogens (their correct classification increasing from the previous 86% to 97%). The derived SAR was tested by applying it to 11 human carcinogens not included in the training set. Their carcinogenicity was correctly predicted for 10 chemicals out of 11.

Carcinogens↗

Changes of immunological patterns of human cancer cells treated in vitro with a triazene compound.

Previous experimental evidence indicates that immunogenicity of mouse tumor cells can be increased by treatment with dacarbazine and other triazene compounds. The present studies have been conducted on the human cell lines H125 (lung cancer), 1246 (melanoma), X3 (EBV-immortalized B cells) subjected to in vitro treatment with 4 (3-methyl-1-triazeno) benzoic acid potassium salt (MTBA). Untreated or drug-treated sublines were tested for susceptibility to allogeneic NK effector cells, either non-stimulated or pretreated with beta-Interferon. In the case of X3 cell line and its MTBA-treated subline the expression of the EBV-associated antigens and the capability of eliciting autologous cytotoxic T lymphocytes (CTL) were also investigated. The results suggest that a modification of membrane antigenic pattern could be induced by MTBA treatment in terms of changes of cell susceptibility to cell-mediated lysis, expression of EBV-related antigens and capability to elicit autologous CTL.

Antigens, Differentiation, B-Lymphocyte↗

Evaluation of postoperative blood coagulation changes in elderly patients undergoing major surgery.

18 elderly patients submitted to major surgery for malignancies or other disease were studied to assess the relationship between changes of blood coagulation factors and inhibitors in the early post-operative period and the appearance of lower limb deep vein thrombosis. A decrease in serum antithrombin III (AT III) Protein C antigen (PC: Ag) and Plasminogen activity (PLG) levels from the second to the fourth postoperative day, together with a simultaneous increase in serum fibrinogen (FG) and von Willebrand Factor (vWF:Ag) antigen levels was observed. In 8 patients, PC:Ag levels dropped below the limit considered at risk to develop DVT (less than 60 U/dl). A patient with the lowest PC:Ag levels had deep vein thrombosis From the analysis of data it was concluded that in the postoperative period, blood coagulation changes occur in elderly patients, predisposing to the risk of deep vein thrombosis.

Aged↗