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Biomedical subjects

M Giuliano

Publications and source records attributed to M Giuliano.

At least 73 records · Page 4Linked to original sources
PubMed1992

Identification of insulin in chick embryo retina during development and its inhibitory effect on DNA synthesis.

Incubation of chick embryo retinal explants with insulin resulted in a pronounced inhibition of thymidine uptake and incorporation into trichloroacetic acid-insoluble fraction. The inhibitory effect was highest with explants from embryos at day 7 and day 8, and thereafter it declined markedly with the age of embryos until day 11. A time-course study of the effect revealed that the inhibition occurred after a lag time; both thymidine uptake and incorporation were not altered significantly after 2-6 h of incubation with insulin, but began to decrease thereafter, reaching the maximum after 16 h. The effect was also dose dependent. After 16 h of incubation, the maximal inhibition (65%) was found with 10(-8) M insulin. Insulin caused similar effects also on thymidine kinase activity. All these effects were obtained by using minimal essential medium without glutamine. The addition of glutamine to the medium reduced the inhibitory effect of insulin. Retinas of chick embryos contain immunoreactive insulin. Retinal immunoreactive insulin was at the highest level (1.12 ng/mg of protein) in the youngest retinas studied (day 6), then it declined with age, reaching the lowest value (0.58 ng/mg of protein) at day 14. This value did not vary significantly during the third week of development. A potential biological role of insulin in retinal development is discussed.

Animals↗
PubMed1992

Therapeutic strategies for postremission treatment in childhood acute myeloid leukemia (AML). The AIEOP experience 1987-1991.

From 1987 to 1990, intensive postremission chemotherapy was compared to autologous bone marrow transplant in previously untreated children with AML who received identical induction therapy with two courses of Daunorubicin (DNR) and conventional dose ARA-C (protocol AIEOP LAM 87). Overall, 121 of the 155 eligible patients achieved complete remission (CR) (78%). Patients in CR who lacked HLA-MLC compatible donor were randomized to receive either autologous BMT (Auto-BMT) or further sequential postremission therapy. Patients with HLA-MLC compatible donor were assigned to allogeneic BMT (Allo-BMT). Projected 3-years disease free survival (DFS) are 58% for Allo-BMT group, 24% for Auto-BMT group, 26% for chemotherapy group and 30% for a group of not randomized patients (intention to treat analysis). On March 1990 a pilot study LAM 87M was initiated. Patients in CR after induction therapy (identical to the previous protocol) receive a single intensification course consisting of high dose ARA-C plus DNR. The study continues to accrue patients.

Acute Disease↗
PubMed1991

Fat body mass and pharmacokinetics of oral 6-mercaptopurine in children with acute lymphoblastic leukemia.

To evaluate the reasons for the wide variability in bioavailability of orally administered 6-mercaptopurine in children with acute lymphoblastic leukemia, we studied several pharmacokinetic parameters of the drug in 18 affected children receiving remission maintenance therapy, and compared them with their anthropometric data and with the results of intestinal function tests. No correlation was found between estimates of small intestinal absorption (the oral lactose tolerance test and 1 h blood xylose test) and 6-mercaptopurine serum levels. Of the anthropometric measurements considered, only the weight/height percentile (an index of the fat body mass) strongly and linearly correlated with the area under the curve of 6-mercaptopurine. The dose of 75 mg of 6-mercaptopurine/m2 of body surface resulted in higher serum concentrations in children below the 75th percentile than in those with a weight/height ratio exceeding the 75th percentile. In conclusion, these data caution about the risk of underdosing 6-mercaptopurine in overweight children when administering it on the basis of body surface area.

Administration, Oral↗
PubMed1990

Surface blebbing and cytoskeletal changes induced in vitro by toxin B from Clostridium difficile: an immunochemical and ultrastructural study.

Clostridium difficile toxin B is a powerful cytopathic agent without enterotoxic activity which is believed to be involved in the pathogenesis of pseudomembranous colitis. Up until today, the mechanisms of toxin B cytotoxicity have not been elucidated. The results of in vitro studies performed on different cell lines by means of immunocytochemical and ultrastructural methods are reported here. Low doses (0.15 ng/ml) of toxin B cause cell rounding and arborization. Higher doses (up to 15 micrograms/ml) induce cell rounding and appearance of numerous surface protrusions with blister or bulb-like features. These "blebs" belong to the potocytotic type, the bleb matrix being devoid of cytoplasmic organelles and filled with ribosomes only. Furthermore, a peculiar role of cytoskeletal apparatus in this phenomenon has been detected. In fact, morphological rearrangement occurs in cytoskeletal elements, mainly represented by the presence, in the blebs, of tubulin and of the actin-binding proteins alpha-actinin, filamin, and calmodulin, while actin and intermediate filaments, keratin and vimentin, appear to be absent. Moreover, beta 2-microglobulin, considered as a surface protein marker, seems to undergo changes in its expression, being absent over the blebbing surface. The results of this study may support the view that C. difficile toxin B affects one or more subcellular components that regulate the structure and function of the actin cytoskeleton.

Bacterial Proteins↗
PubMed1990

Interaction of Clostridium difficile toxin A with cultured cells: cytoskeletal changes and nuclear polarization.

Experiments done on in vitro-cultured cells exposed to toxin A from C. difficile showed a series of cytopathologic changes leading to cell retraction and rounding accompanied by the marginalization of the nucleus, which localized at one pole of the cell. Cytoskeleton appeared to be strongly involved in such modifications. In particular, the microfilament system seemed to be involved in cell retraction, while microtubule network integrity and function seemed to be necessary for the nuclear displacement. The carboxylic ionophore monensin completely blocked the cytopathic effect when added with the toxin. The serine protease inhibitor chymostatin appeared to be protective also upon addition long after the end of the binding step. The Ca2(+)-dependent cytosolic protease inhibitors antipain and leupeptin were uneffective in protecting cells. Thus, our results suggest the involvement of an acidic compartment and the action of a serine protease in toxin A-induced cytopathic effect.

Animals↗
PubMed1990

Macular recovery function (nyctometry) in diabetics without and with early retinopathy.

Nyctometry was used to assess macular recovery function in 234 diabetic patients; their retinopathy ranged from no retinopathy (99) to early background retinopathy (135). None had visual symptoms or macular oedema. Abnormal (reduced) nyctometry findings were significantly and directly related to the deterioration of diabetic retinopathy. There was no significant association between reduced or normal nyctometry findings and glycaemia at the time of the examination. The value of nyctometry in screening and follow-up is discussed.

Adaptation, Ocular↗
PubMed1989

Inhibition of DNA synthesis in chick embryo retinas, in vitro, by a factor from fetal bovine serum.

Fetal bovine serum inhibited deoxyribonucleic acid (DNA) synthesis in chick embryo retina explants. The inhibitory activity was precipitated from fetal bovine serum by 45% saturated ammonium sulfate and isolated by means of Sephadex G-100 and Bio-Gel P-60 columns as a peak with an apparent molecular weight of 7000 Da. DNA-inhibiting activity was heat- and acid-stable and was destroyed by dithiothreitol and alkaline treatment. The purified factor inhibited similarly both DNA synthesis and thymidine kinase activity; 50% inhibitory effect was found with 160 ng, 17 h after the addition into the incubation medium.

Animals↗
PubMed1989

Effects of Clostridium difficile toxins A and B on cytoskeleton organization in HEp-2 cells: a comparative morphological study.

A comparative study on the effects of toxin A and toxin B from Clostridium difficile on HEp-2 cells was carried out. Both toxins caused cell retraction and rounding and seemed to exert their effect on cell morphology via a rearrangement of actin and alpha-actinin microfilaments. Such a rearrangement occurred at an early stage, when no change in microtubular and cytokeratin systems was detectable. Nevertheless, several structural modifications accompanying the cytopathological process induced by toxins A and B appeared to be quite different. In particular, toxin B-treated cells showed an arborized phenotype as a result of cell retraction and rounding, whereas toxin A caused cell rounding without arborization. Moreover, nuclear polarization following disorganization of the microfilament system was only observed in toxin A-treated cells. The structural features distinguishing intoxication processes induced by the two toxins probably reflect a different mechanism of action and suggest the presence of a distinct subcellular component as a primary target for each toxin.

Bacterial Proteins↗
PubMed1989

Effects on oral and intestinal microfloras of norfloxacin and pefloxacin for selective decontamination in bone marrow transplant patients.

We monitored the modifications of oral and intestinal microfloras of 10 allogeneic bone marrow recipients who received randomly either norfloxacin or pefloxacin (400 mg three times a day) as selective decontamination for infection prevention. After 1 week of treatment, in all patients members of the family Enterobacteriaceae were no longer detectable and in all but one pefloxacin-treated patient enterococci were also eliminated in the intestine. The anaerobic flora was not affected, with the exception of Bacteroides spp., markedly reduced after treatment with pefloxacin. In most patients the most striking effect was the increase in staphylococcal counts. These strains were found to be resistant to both quinolones in the study. Less consistent changes were observed in oral flora. No relevant difference could be demonstrated between the two regimens on bacterial counts either in feces or in saliva. This study shows the efficacy of both quinolones in eradicating gram-negative bacilli in the alimentary tract of bone marrow transplant patients; however, the finding of the overgrowth of resistant gram-positive organisms during treatment with these agents deserves further evaluation.

Adult↗
PubMed1989

Laboratory screening of monoclonal gammopathies: incidence of serum monoclonal immunoglobulins during a five years survey in a general hospital.

During a five years survey of unselected serum protein electrophoreses in a general hospital, 2347 sera (0.95%) were found to be positive for one or more monoclonal immunoglobulins. Class and type distribution of monoclonal immunoglobulins (characterized by means of immunofixation electrophoresis) mostly corresponded with the literature data. Nevertheless, higher incidence and lower mean age at detection were observed for IgG monoclonal components. This finding is probably related to the discovery of a large number of micro-monoclonal immunoglobulins with no association with B-lymphoproliferative disorders, mostly belonging to the IgG class and affecting younger people. The need is stressed for a widespread standardization of the techniques employed for detection and characterization of monoclonal immunoglobulins, in order to obtain more comparable results.

Aged↗
PubMed1989

Do colon and rectum exhibit an opposite cancer risk trend versus cholecystectomy? A case--double control study.

A case-double control study on 318 personally interviewed patients with large bowel neoplasia has been carried out to establish the possible role of cholecystectomy in the development of colorectal cancer. The dietary habits both of the cancer patients and control subjects were investigated. All controls were considered free of neoplastic lesions on the basis of a negative fecal occult blood test. Data from the study showed that the prevalence of cholecystectomy in the overall patients was similar to that of the two control groups. However, analysing the data for colon and rectum, the relative risk of colonic cancer after cholecystectomy was significantly increased in males (RR = 2.75; p less than 0.05), whereas that of rectal cancer appeared to be decreased in females (RR = 0.18; p less than 0.02). Subsite analysis demonstrated that right-sided neoplasia after long-standing cholecystectomy (greater than or equal to 10 years) was responsible for the increased colonic risk. In conclusion, the present data support the hypothesis that cholecystectomy may be considered a risk factor for right-sided colon cancer, but indicate that this operation seems to play a protective role for rectal cancer.

Aged↗
PubMed1988

Colonization resistance of the human intestinal microflora: testing the hypothesis in normal volunteers.

Colonization resistance is the mechanism whereby the intestinal microflora protects itself against incursion by new and often harmful microorganisms. Some authors have claimed that colonization resistance is related to the integrity of the anaerobic flora, but this point has not been established in humans. In previous studies in our laboratory cefoxitin, piperacillin, cefoperazone or aztreonam were administered intravenously to healthy volunteers in order to study changes in the intestinal flora and acquisition of new strains. Seven of 16 antibiotic-treated subjects were colonized with gram-negative bacilli, but no correlation was observed between this colonization and the suppression of either anaerobes or any other component of the fecal flora. Marked strains of Escherichia coli and Pseudomonas aeruginosa were also administered by mouth in order to test acquisition of new bacteria. The fed bacteria were found in the stools of both antibiotic-treated and control subjects; the antibiotics had no apparent influence on the ability of these strains to colonize the intestinal tract. Our work, along with findings of others, supports the concept that colonization resistance occurs in humans and is diminished by antibiotic administration. However, it does not support the hypothesis that colonization resistance is related to the anaerobic microflora.

Anti-Bacterial Agents↗
PubMed1988

Morphological and biochemical effects of glucocorticoids in chick embryo hepatocytes during development.

The administration in ovo of hydrocortisone-21-phosphate caused, in chick embryo liver, a reduction of the number of hepatocytes which can be isolated from 1 mg dry weight of liver and a marked increase of their size. Moreover, the treatment diminished the incorporation of thymidine into acid-insoluble fraction in these cells whilst it augmented the content of protein, RNA, DNA and the level of thymidine kinase/cell. These effects were highest at 8-10 days, then declined with the age, disappearing after 18th day of incubation. Similar effects were obtained by injecting other glucocorticoids or ACTH. Combined treatment with metopirone abolished the effects found with ACTH, but did not modify the action of hydrocortisone. These findings suggest that glucocorticoids interfere with the proliferative cycle of hepatocytes by inhibiting the mitotic phase and favouring the production of abnormally large cells.

Adrenocorticotropic Hormone↗
PubMed1987

Influence of hydrocortisone on chick embryo retina development.

Treatment of chick embryos in ovo with hydrocortisone-21-phosphate (a single dose of 150 micrograms) caused a marked reduction of retinal thymidine kinase activity 24 h later. The inhibitory effect was highest (65-70%) in 8-10-day-old embryos and declined with age, disappearing after day 15. It was accompanied by a reduction in thickness of the retinal layers. Adrenocorticotropic hormone (ACTH) treatment (10 micrograms daily for 2 days) also produced an age-dependent inhibitory effect on retinal thymidine kinase, whereas treatment with a single dose of 200 micrograms of metopirone, a compound that prevents the 11 beta-hydroxylation of steroid molecules in the adrenal glands, impeded the decrease in thymidine kinase activity that normally occurs in chick embryo retina after day 9 of development. In addition, metopirone prevented the inhibition exerted by ACTH on thymidine kinase activity but had no effect on the action of hydrocortisone.

Adrenocorticotropic Hormone↗
PubMed1987

Effect of broad-spectrum parenteral antibiotics on composition of intestinal microflora of humans.

We compared the effects of four beta-lactam drugs with widely differing antibacterial and pharmacological properties on the composition of the intestinal flora. Cefoxitin, piperacillin, cefoperazone, and aztreonam were given intravenously for 9 days to healthy volunteers. Cefoperazone reduced the numbers of aerobic and anaerobic bacteria to undetectable levels. At the other extreme, cefoxitin had little effect on the normal flora. Aztreonam markedly reduced the numbers of aerobes, whereas piperacillin had a variable effect on both aerobic and anaerobic bacteria. There was extensive overgrowth of enterococci in subjects given cefoxitin or aztreonam, which have little activity against this species, and of yeasts in subjects given cefoperazone or piperacillin. Cefoperazone reached concentrations of 2,727 to 8,840 micrograms/g in the feces, whereas the other agents were generally undetectable. These results show that the new beta-lactam antibiotics produce widely varying effects on the fecal microflora after parenteral administration and that these effects are consistent with the antibacterial and pharmacological properties of the drugs.

Adult↗