[Major hepatic resection in children: changes in the hepatic function indices].
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Biomedical subjects
Publications and source records attributed to G Galli.
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The relevance of cytologic procedures in the diagnosis of malignant pleural effusions is evaluated. Pleural fluid sample obtained from 48 patients with malignant disease (39 metastatic tumors, 9 mesotheliomas), were studied to search for cancer cells. The results were: 32 (66.6%) patients had a cytologic diagnosis of malignant pleural effusions; 16 malignant specimens were not confirm by pleural fluid cytologic analysis. In our experience the cytologic diagnosis of malignant pleural effusions are more frequent in metastatic disease, especially in lung cancer.
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F(ab')2 fragments of anti-carcinoembryonic antigen (CEA) monoclonal antibody F023C5, determined to be more suitable than intact IgG and Fab fragments for immunoscintigraphy, were labeled with 131I or conjugated to DTPA for instant 111In-labeling, and administered i.v. (2-3 mCi/0.5 mg) to 509 patients in 11 nuclear medicine departments: 284 patients had gastrointestinal adenocarcinomas, 204 had nongastrointestinal adenocarcinomas and 21 were control; serum CEA was elevated in 169 patients, normal in 115, and not determined in 225. The following results were obtained: (a) no adverse reactions; (b) tumor imaging in 324 patients (in particular, in 81.5% CEA-seropositive and in 69.0% CEA-seronegative patients); (c) no significant difference in sensitivity among the results of the 11 departments; (d) no significant difference in overall sensitivity between 131I-and 111In-labeled immunoradiopharmaceuticals; (e) the fraction of documented lesions imaged was 73.3% in CEA-seropositive and 53.7% in CEA-seronegative patients; (f) the detection of liver metastases was hampered, particularly when using the 111In-labeled reagent, by nonspecific radioactivity uptake; (g) the major cause of negative immunoscintigraphy results was a lack of CEA in tumor lesions, as documented by immunohistochemistry; (h) lesion size is also important since the sensitivity was 64% for lesions up to 2 cm in diameter and 84% for larger lesions; (i) many "unexpected" radiolocalizations were recorded. Most were identified as occult tumor lesions. In 35 patients, this finding contributed to the early detection of tumor recurrences.
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The effect of chenodeoxycholic (CDCA), ursodeoxycholic (UDCA), tauroursodeoxycholic (TUDCA), cholic (CA), ursocholic (UCA) acids, analogues of CDCA and UDCA with a cyclopropyl ring at C22, C23 (cypro-CDCA and cypro-UDCA) and 23-methylursodeoxycholic acid (MUDCA) on cholesterol 7 alpha-hydroxylase was studied in rat liver microsomes. Cypro-analogues consisted of a mixture of four diasteroisomers, while MUDCA was the racemic mixture of two enantiomers. Each steroid was added to liver microsomes at concentrations ranging from 10 to 200 microM. With the exception of UCA and CA, all the bile acids inhibited cholesterol 7 alpha-hydroxylase activity. The inhibition shown by cypro-CDCA and cypro-UDCA was stronger than that observed with the corresponding natural compounds. 22S,23S cypro-UDCA exhibited an inhibitory effect which was more pronounced than that of the diasteroisomer mixture. The isomer 22R,23S was less effective and decreased cholesterol 7 alpha-hydroxylase activity in a manner comparable to that of UDCA. The effect of CDCA, UDCA and the cyclopropyl analogues was also tested with respect to HMG-CoA reductase and acylCoA cholesterol acyltransferase (ACAT) activities. ACAT was stimulated by the isomer 22S,23S cypro-UDCA but not affected by the other bile acids. No effect was observed as regards HMG-CoA reductase.
The aim of this study was to characterize the plasma lipoprotein pattern and some aspects of cholesterol metabolism in a line of hyperlipemic male rats. Plasma cholesterol and triglycerides were increased about 3-fold as compared to control animals (238 vs. 75 and 185 vs. 59 mg/dl respectively). The plasma lipoprotein distribution and the chemical composition of the isolated lipoproteins was unaffected. Plasma triglyceride production rate was increased (40%, P less than 0.01) and post-heparin lipoprotein lipase activity in plasma decreased (-28%, P less than 0.01) in the hyperlipemic rat. The activity of 3 enzymes involved in cholesterol metabolism (HMG-CoA reductase, cholesterol 7 alpha-hydroxylase, and acyl-CoA cholesterol-acyltransferase) did not differ from control values. 3H2O incorporation into digitonin-precipitable sterols, however, was significantly higher than in controls. This finding was due, in part, to an increased liver weight in the hyperlipemic animals. Furthermore kinetic data using 125I-LDL showed that the fractional catabolic rate of lipoprotein was within the normal range, while the synthetic rate of LDL protein was increased (0.67 vs. 0.3 mg/kg/h, P less than 0.01) in the hyperlipemic rat. These observations suggest that multiple metabolic defects underline the hyperlipemia observed in this animal model.
A strain of Pseudomonas sp., SMP1, isolated from a soil sample collected in the Monterotondo area (Rome), secreted isoamylase activity into the culture medium. The enzyme was purified and optimal reaction and stability conditions were determined by varying pH and temperature. The chemico-physical properties of the enzyme were similar to those of the isoamylase purified in Japan more than 20 years ago from 'Pseudomonas amyloderamosa' strain SB15. A genomic library of SMP1 was prepared in Escherichia coli using pUC12 as vector. Two isoamylase-producing colonies were identified out of 6300 screened. The hybrid plasmids isolated from the two clones showed common restriction patterns. The chromosomal portion of one of these plasmids (pSM257) was completely sequenced. Comparison between the deduced amino acid sequence of the isoamylase and the published sequences of other amylolytic enzymes showed the presence of conserved domains.
Insulin-like growth factor-I (IGF-I) stimulates the growth of thyroid cells of different animal species. However, conflicting results have been reported as regards the function and mechanism of the action of IGF-I at the thyroid level. This study was designed to determine whether normal human thyroid cells have IGF-I receptors and whether IGF-I could act on such cells through an autocrine mechanism. Human thyroid follicular cells in primary culture, not contaminated by fibroblasts, were used. They had specific and saturable binding sites for IGF-I, as revealed by radiolabeled binding method, and displayed an average receptor number of 2000/cell. Under the same experimental conditions, insulin receptors were not detectable. Human thyroid follicular cells secreted IGF-I into the culture medium, as assessed by a specific chemiluminescent immunoassay. The IGF-I secretory process was detectable for at least 12 days of culture, but a high degree of variability has been found among individual samples. Acid-gel chromatography demonstrated that IGF-I and a higher mol wt IGF-I, most likely IGF-I bound to its binding protein, were secreted by human thyroid cells. TSH stimulated the secretion of the two molecules in normal human thyroid cells. The TSH effect on IGF-I secretion was concentration dependent between 0.1 nmol/L and 0.1 mumol/L. GH stimulated IGF-I synthesis by thyroid cells in a concentration range from 20-200 micrograms/mL. Since binding studies demonstrated the presence of IGF-I receptors on human thyroid cells, IGF-I probably regulates human thyroid function through an autocrine mechanism.
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The in vitro effects of albumin (150-600 microM) on arachidonate metabolism are compared in two types of circulating cells, platelets and neutrophils. The effect of this plasma protein on a functional aspect common to both these blood components, i.e. aggregation, was also investigated. Bovine serum albumin (BSA) significantly inhibited thromboxane B2 formation by washed platelets stimulated with threshold concentrations of collagen. In addition, this protein profoundly affected the formation of the major products via the lipoxygenase pathways, i.e., 12-hydroxyeicosatetraenoic acid and leukotriene B4 by platelets and neutrophils, respectively. This inhibitory effect was also confirmed for both types of cells considered on aggregation. Albumins of human origin and human plasma behaved similarly to BSA on the above parameters. Although the mechanism(s) responsible for the described effects require(s) additional studies, albumin, affecting platelet and neutrophil arachidonate metabolism, as well as the aggregatory response, might influence, in some conditions, cell activation.
Preliminary results from the relationship between aging and mucociliary clearance of inhaled 99-Tc human albumin particles (0.92-2.5 microns) are reported from two groups of healthy non-smokers: 1) 20-61-year-old (mean 42 years) and 2) 71-90-year-old (mean 79.5 years). The analytical procedure is presented, and on the basis of the analysis it is concluded that there is evidence for an age-related decline of the mucociliary clearance by a bi-phasic curve, similar to those reported in the literature for other physiological functions.
Tomographic images with electronic density can be obtained by irradiation with a monoenergetic beam and detection of the scattered Compton photons. The results of a dosimetric study on the beam of an irradiating Compton unit (equipped with two 192Ir 277.5 GBq sources) are here presented. Doses along the central axis of the beam were measured using thermoluminescent LIF-100 dosimeters. Measurements were taken both in water (RFA-3 Therados) and in cork phantoms. Isodose distributions were estimated by reading the automatic photo-densitometry of radiographic films. A simple algorithm for calculating depth dose values was obtained by analyzing experimental data. The mean absorbed dose (mad) in soft tissues (up to 25 cm deep) was 2.81 mGy for a work load of 7.4 X 10(11) Bq min. The mad in standard thorax was calculated also, which amounted to 3.78 mGy.
The effects of single oral administrations of acetylsalicylic acid (ASA, 500 mg), indomethacin (Indo, 50 mg) and sodium salicylate (NaSal, 400 mg) on platelet aggregation and on the thromboxane B2 (TXB2) and 12-hydroxyeicosatetraenoic acid (12-HETE) synthesis by platelet rich plasma (PRP) stimulated with collagen were evaluated. While both ASA and Indo significantly inhibited TXB2 synthesis and platelet aggregation, significant reduction of 12-HETE formation at 2 and 6 h after the administration of the drug, was detected only in subjects who ingested ASA. NaSal did not affect any of the tested parameters. The comparison of the effect of ASA (200 mg) on 12-HETE synthesis in washed platelets and PRP shows that the drug is able to affect this parameter only in PRP. To obtain a constant inhibition of 12-HETE synthesis in PRP over a 24 h period, a repeated ASA treatment schedule was assessed (ASA 200 mg every 6 h for 5 times). TXB2 synthesis in PRP was almost completely suppressed at 2 h after the first ASA administration and inhibition remained constant up to 48 h after the last ASA intake. As far as 12-HETE synthesis by stimulated PRP is concerned, a significant reduction of this parameter was detected at 4 h after the first drug administration and the levels remained almost constant following the repeated administrations during a 24 h period. These data indicate that ASA, but not Indo and NaSal, significantly affect not only TXB2 synthesis but also 12-HETE formation in PRP. The lack of the effect of ASA administration on 12-HETE, found when studies were carried out in washed platelets, indicates that the drug requires the presence of plasma factors for its activity on the formation of 12-lipoxygenase products by platelets.
The established mouse epidermis-derived cell line HEL/30 was incubated in the presence of 3H arachidonic acid (AA) for 1 h. After medium removal, cells were reincubated with fresh medium in the presence or absence of the calcium ionophore A23187 and tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The AA metabolites formed were extracted from cell-free medium and analyzed using TLC and HPLC. The distribution of the recovered radioactivity showed PGE2, 15-hydroxy-eicosatetraenoic acid (15-HETE), and leukotriene B4 (LTB4), as major products of AA metabolism. The presence of calcium ionophore A23187 increased the release of radioactivity, without affecting the profile of metabolites present in the medium. TPA elicited a preferential increase of cycloxygenase metabolism, this effect being reversed by indomethacin. 5,8,11,14-eicosatetraynoic acid (ETYA) almost completely inhibited LT and HETE formation in A23187 and TPA-treated cells. The results show that HEL/30 cells are able to metabolize AA via both cyclo- and lipoxygenase pathways and that these activities can be modified by chemical means. This cell line might be a suitable tool for studying the involvement of arachidonic acid cascade in cell response to exogenous stimuli.
The effects of a single oral administration of acetylsalicylic acid (500 mg), indomethacin (50 mg) and piroxicam (40 mg) to healthy volunteers on functional and biochemical parameters of platelets, polymorphonuclear (PMN) and mononuclear (MNL) leukocytes were evaluated. Blood was collected before and two hours after the drug intake and blood cells separated according to conventional techniques. The considered drugs almost completely suppressed the aggregation of platelets, whereas they did not affect either PMN and MNL aggregation. Superoxide anion generation by leukocytes was (PMN), or no effect (MNL) was observed after piroxicam and indomethacin respectively. The formation of arachidonate metabolites via the 5-lipoxygenase pathway by PMN and MNL challenged with 10 microM A23187 was unchanged following aspirin and indomethacin. In this respect a selective increase of 5-HETE and LTC4 synthesis by MNL only was detected after piroxicam administration. The three drugs similarly reduced TXB2 synthesis by platelets and PMN (-80% for aspirin and indomethacin, and -40% for piroxicam). As far as MNL is concerned, aspirin inhibited this metabolite by 80%, while indomethacin reduced it by 40% only. In contrast piroxicam increased TXB2 synthesis by stimulated MNL. It can be concluded that the considered antiinflammatory drugs 1) differently affect the cyclooxygenase enzyme in platelets and leukocytes; 2) at variance with the situation in platelets, the inhibition of thromboxane formation by leukocytes is not related to modifications of cellular function; 3) the formation of arachidonate metabolites via the 5-lipoxygenase pathway is affected by piroxicam only.
An anaphylactic reaction was induced with the specific antigen (1 mg Ovalbumin) in perfused lungs from actively sensitized guinea-pigs in order to evaluate the ability of the ginkgolide BN-52021 (0.4, 4, 40 micrograms/ml) to modulate the mediator release. The ginkgolide reduces in a dose dependent manner the release of histamine (22%, 45% and 75% of inhibition), TXB2 (77% of inhibition at the maximal dose used) and of SRS-A to a lower extent (only 33% at the higher dose). BN-52021 was still powerful in reducing histamine release induced by immunological reaction in indomethacin treated animals. In conclusion, the present "in-vitro" results confirm the beneficial activity of this ginkgolide, already demonstrated by the same Authors in "in-vivo" experiment, in anaphylactic reactions, and further substantiate the wider spectrum of action of the ginkgolide beside its specific PAF receptor antagonistic activity.