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Biomedical subjects

G Conti

Publications and source records attributed to G Conti.

At least 19 recordsLinked to original sources

Detection of IgA and IgM antibodies to HIV-1 in neonates by radioimmune western blotting.

OBJECTIVE: To detect infection with HIV-1 by IgA and IgM response at birth in children born to HIV-1 seropositive mothers. DESIGN: Western blotting and radioimmune western blotting on stored sera from infected and uninfected babies born to HIV-1 seropositive mothers. Sera were pretreated to remove IgG. SETTING: Parma and Bologna, Italy. SUBJECTS: 12 infected and five uninfected babies born to HIV-1 seropositive mothers and three babies born to seronegative mothers. MAIN OUTCOME MEASURES: Effectiveness of western blotting and radioimmune western blotting in detecting antibodies to HIV-1 gene products. RESULTS: With conventional western blotting we found IgA class antibodies to HIV-1 proteins in serum from three out of 12 infected children; in two of these three the serum was collected at age 3 months (positive controls). Radioimmune western blotting detected both IgA and IgM antibodies in serum from all infected children tested, whereas all serum from uninfected children born to seropositive and seronegative mothers showed no such antibodies. CONCLUSION: Although the technique should be tested on more patients, radioimmune western blotting seems to be a valuable tool for serological diagnosis of congenital HIV-1 infection at birth in neonates born to seropositive mothers.

Blotting, Western

Expression of genes encoding receptors for IgG (FcRIII) and for C3b/C4b (Crry) in rat sciatic nerve during development and Wallerian degeneration.

Northern blots were used to examine the expression of genes encoding receptors for IgG (FcRIII) and for C3b/C4b (Crry) in rat sciatic nerve during development and Wallerian degeneration. Steady state levels of FcRIII (1.4 kb) and Crry (1.9 and 2.1 kb) mRNAs were higher in adult rat nerves than in 6 day and 21 day postnatal rat nerves, indicating that the expression of these receptors is developmentally regulated. The FcRIII and Crry cDNA probes also hybridized with total RNA from 3 day old rat Schwann cells and from adult rat peritoneal macrophages. The size of the FcRIII mRNA expressed by cultured Schwann cells (1.6 kb) differed from that expressed by peritoneal macrophages (1.4 kb); the two may be splice variants of one transcript or products of related genes. Peritoneal macrophages contained approximately 100 times higher FcRIII mRNA levels than Schwann cells. In contrast, steady state levels of both 1.9 and 2.1 kb Crry mRNAs were similar in cultured Schwann cells and macrophages. Nerve transection induced a generalized increase in the level of sciatic FcRIII mRNA (1.4 kb) 3 days post-surgery, whereas the level of Crry mRNA was increased only in the nerve segment immediately to the cut. The increase of FcRIII mRNA that occurred in Wallerian degeneration was most likely due to infiltration of macrophages, as FcRIII mRNA-positive macrophages were demonstrated in the degenerating nerves by in situ hybridization. FcRIII mRNA-positive macrophages were not found in normal nerve. The functions of FcRIII and Crry in peripheral nerves are uncertain, but they may be of significance in phagocytosis, antibody-dependent cellular cytotoxicity, and in local immune regulation.

Aging

A fibre optics system for the evaluation of airway pressure in mechanically ventilated patients.

OBJECTIVE: The present study was intended to evaluate the "in vivo" endotracheal (ET) tube resistance and respiratory mechanics in mechanically ventilated patients with respiratory failure by using fiber optic catheters. DESIGN: Two fiber optic catheters, consisting of a thin probe with a pressure transducer on the tip, were used. The first was placed at the proximal side of the ET tube and the second was positioned distally beyond the end. A low compliant air-filled catheter connected to a traditional pressure transducer was placed close to the proximal fiber optic device to compare the pressure values obtained with both systems. SETTING: The study was performed in the General Intensive Care Unit of Rome "La Sapienza", University Hospital. PATIENTS AND PARTICIPANTS: Seven patients admitted for the management of acute respiratory failure of different etiologies were included in the protocol. All the patients were intubated and mechanically ventilated for at least 48 h prior to the investigation. MEASUREMENTS AND RESULTS: The endotracheal tube resistance was obtained both by the end-inspiratory occlusion method and measuring pressure proximally and distally to the ET tube. The measurement of respiratory mechanics was obtained proximally and distally to the ET tube. Different flows and tidal volume changes were performed. The results showed that the fiber optic device gives an adequate evaluation of airway pressure and the possibility for an easy detection of obstructions and/or deformations of the ET tube. The area described by inspiratory and expiratory pressure recorded at both sides of the ET tube showed a positive relationship between the surface and flows while no surface changes were shown when the tidal volumes were modified. Thoraco-pulmonary compliance measured proximally and distally to the ET tube gave rise to a small and statistically insignificant difference. CONCLUSION: This study confirms that 48 h after the positioning of ET tubes the airflow resistance is significantly higher than might be expected from the "in vitro" data. The presence of the endotracheal tube can interfere with the evaluation of thoraco-pulmonary mechanics, particularly in dynamic conditions. The fiber optic system represents an interesting and simple tool for the evaluation of ET tube resistance and pulmonary mechanics in patients undergoing mechanical ventilation.

Adult

The induction of mitotic chromosome malsegregation in Aspergillus nidulans. Quantitative structure activity relationship (OSAR) analysis with chlorinated aliphatic hydrocarbons.

The biological activity of 24 chlorinated aliphatic hydrocarbons has been studied in the mold Aspergillus nidulans. The ability to induce chromosome malsegregation, lethality and mitotic growth arrest has been experimentally determined for each chemical. These data, together with those of 11 related compounds previously investigated, generated a data base which was used for quantitative structure-activity relationship (QSAR) analysis. To this aim, both physico-chemical descriptors and electronic parameters of each compound have been calculated and included in the analysis. The QSAR analysis indicated that toxic effects induced by chlorinated aliphatics in A. nidulans are mainly dependent on steric factors, as indicated by the correlation with molar refractivity (MR). Conversely, the ease with which they accept electrons, parametrized by LUMO (energy of the lowest unoccupied molecular orbital), plays a prevailing role in determining the aneuploidizing properties. An involvement of free radicals, generated by the reductive metabolism of haloalkanes, is hypothesized as an explanation of the data.

Aneuploidy

Peripheral nervous system (PNS) expression of mRNAs encoding myelin proteins and Fc gamma RIII during experimental allergic neuritis.

Experimental allergic neuritis (EAN) was induced in Lewis rats by injection of 'SP26', a peptide homologous to amino acids 53-78 of bovine myelin P2 protein, in complete Freund's adjuvant. The rats developed signs of EAN which began on day 14, were maximal on day 18, and had subsided by day 30. RNA content of cauda equina and sciatic nerves increased more than 2-fold at the height of EAN. Expression of myelin P0 and P1 mRNAs did not fall during EAN, nor rise during recovery. Fc gamma R mRNA, which encodes Fc gamma RIII, an immunoglobulin-binding protein mediating activation of natural killer cells and macrophages by immune complexes, was transiently, but markedly induced in scattered endoneural cells, presumably macrophages, in cauda equina and sciatic nerves during the period of increasing weakness.

Amino Acid Isomerases

Early prediction of successful weaning during pressure support ventilation in chronic obstructive pulmonary disease patients.

OBJECTIVE: The aim of this study was to examine variables for early prediction of successful weaning in chronic obstructive pulmonary disease (COPD) patients during pressure support ventilation weaning. DESIGN: Thirteen COPD patients were prospectively studied to compare the respiratory pattern (inspiratory time, expiratory time, total breath cycle duration, tidal volume, respiratory rate, minute ventilation), the respiratory drive (airway occlusion pressure at 0.1 sec, tidal volume/inspiratory time), and blood gases after 30 mins of pressure support weaning. SETTING: The study was performed in the 20-bed General Critical Care Unit of the Rome "La Sapienza" University Hospital. PATIENTS: We evaluated 13 consecutive COPD patients fulfilling the standard weaning criteria (including clinical status, blood gases, forced vital capacity, maximum inspiratory pressure, and spontaneous respiratory rate after a 30-min T-piece trial) in which we compared respiratory pattern, respiratory drive, and blood gases after 30 mins of pressure support weaning. MEASUREMENTS AND MAIN RESULTS: After 30 mins of pressure support ventilation weaning (pressure support level 20 cm H2O), we measured respiratory pattern (airway pressure and airflow tracing), airway occlusion pressure at 0.1 sec (occluding the inspiratory line during expiration with a rubber balloon), tidal volume/inspiratory time, maximal inspiratory pressure, and blood gases. According to the result of the weaning trial, the patients were divided into two groups (not weaned and weaned), and the statistical difference between the evaluated variables was analyzed in weaned and not weaned groups. We did not observe a significant difference in breathing pattern data and arterial blood gases between weaned and not weaned patients. By contrast, airway occlusion pressure at 0.1 sec and maximum inspiratory pressure measured after 30 mins of weaning trial appeared significantly (p less than .001) different in patients in whom the weaning trial succeeded or failed. Considering maximum inspiratory pressure, we could not separate weaned from not weaned patients, while all patients showing values of airway occlusion pressure at 0.1 sec less than 4.5 cm H2O were easily weaned. CONCLUSIONS: This study confirms that conventional weaning criteria are often inadequate in predicting successful weaning of COPD patients, while airway occlusion pressure at 0.1 sec during the first phase of pressure support ventilation weaning can represent a good weaning predictor.

Aged

Effects of low-dose propofol administration on central respiratory drive, gas exchanges and respiratory pattern.

The effects of sedative-hypnotic doses of propofol on respiratory drive and pattern have not yet been extensively described. Repeated small boluses of propofol (0.6-0.3 mg.kg-1) were administered to ten ASA I patients undergoing carpal tunnel release using regional anaesthesia. Airway pressure, capnography and pneumotachography were continuously recorded. With respect to basal values, no significant variations of respiratory rate, minute volume, tidal volume, inspiratory and expiratory time, total expiratory cycle, Ti/Ttot, TV/Ti, P0.1, EtCO2 and blood gas analysis were observed. Low doses of propofol, to maintain conscious sedation of light sleep, have not been shown to cause respiratory depression.

Ambulatory Surgical Procedures

Potentiation of medroxyprogesterone acetate antineoplastic activity by histidine in rat mammary tumours.

The antitumour activity of arginine, histidine and medroxyprogesterone acetate (MPA) was studied in female rats with dimethylbenzanthracene (DMBA)-induced mammary adenocarcinomas. After 15 days of treatment, regression was observed in 4 of 19 (21%), 3 of 18 (16.7%) and 22 of 59 (37.3%) tumours taken from rats given arginine, histidine or MPA, respectively. A total of 17 rats with tumours that had been non-responsive to MPA were then treated with MPA plus histidine for 15 more days; the growth of 3 lesions (17.6%) was arrested, and 5 tumours (29.4%) regressed markedly. The antineoplastic activity of MPA was found to be related to the oestrogen-(ER) and progesterone-receptor (PgR) concentrations measured in the tumours before the start of treatment, whereas that of arginine and histidine appeared to be independent of receptor status. A significant reduction in serum prolactin (PRL) levels occurred in rats that were responsive to MPA alone or to MPA plus histidine. In tumours taken from the same rats, the PRL receptor content was also significantly increased in comparison with that in non-responsive tumours. In contrast, serum PRL levels increased significantly in rats with tumours that were non-responsive to MPA, whereas no change in serum PRL or PRL receptor levels was observed in rats treated with arginine or histidine. Histidine showed the ability to increase the number of ERs and PgRs in responsive tumours; this could have been responsible for the unexpected potentiation of MPA antineoplastic activity. In contrast, the levels of ER and PgR in uteri taken from the same rats were not modified. Furthermore, the addition in vitro of histidine to cytosols obtained from tumours of control animals did not influence ER and PgR concentrations. These results suggest that the effect of histidine on ER and PgR levels is probably specific for tumour tissue and is not due to a direct activity.

Animals

Mutagenicity spectra in bacterial strains of airborne and engine exhaust particulate extracts.

The mutagenicity spectra of the organic extracts of both airborne particulate matter and diesel and gasoline soot particles were determined using a battery of 9 bacterial strains of different genetic specificity. The assays with crude extracts and with fractionated acidic, neutral and basic components revealed striking differences in the patterns of mutagenic responses produced by each of the complex mixtures investigated. The mutagenicity of air particulate matter was shown to depend mainly on direct-acting acidic and neutral compounds, with a lesser contribution of basic promutagens which required exogenous metabolic activation by liver S9. The assays with a diesel soot extract indicated the prevailing contribution of direct-acting acidic and neutral compounds, and suggested an important role also for nitro derivatives other than nitropyrenes. The gasoline exhaust was characterized by powerful promutagenic compounds, belonging to either the acidic, neutral or basic fractions. The implications of these results are discussed with respect to the contribution of engine exhausts to air pollution, and the possible use of mutagenicity spectra in the analysis of environmental complex mixtures.

Air Pollutants

In vitro studies with nine known or suspected spindle poisons: results in tests for chromosome malsegregation in Aspergillus nidulans.

Within the framework of a coordinated collaborative study for evaluating assays for aneuploidy, nine known or suspected spindle poisons were tested in mitotic segregation assays with Aspergillus nidulans. Experiments with A. nidulans diploid strain P1 revealed a statistically significant increase of whole chromosome segregants (non-disjunctional diploids and haploids) after treatments with chloral hydrate (CH), thiabendazole (TB), thimerosal (TM) econazole (EZ) and hydroquinone (HQ). The latter two chemicals also increased the frequency of mitotic cross-overs. Colchicine (COL), diazepam (DZ), cadmium chloride (CD) and pyrimethamine (PY) were ineffective. Further experiments with CH, TB, TM and EZ in the haploid strain 35 demonstrated that CH, TB and TM induced hyperploid types, thus indicating a primary effect on chromosome segregation in A. nidulans. However, since EZ did not induce putative hyperploids in strain 35 and trisomics in diploid 31, it is suggested that EZ affects chromosome segregation by an indirect mechanism, possibly related to induced structural chromosome damage, as previously shown for HQ.

Aneuploidy

Defective insertion of haemagglutinin as a cause of abortivity of influenza A viruses in HeLa 229 cells.

A number of experimental data demonstrate that certain mammalian cells are unable to replicate Influenza viruses type A. In these cellular hosts the viruses can efficiently perform their biological as well as biochemical activities but the production of mature viral particles is greatly restricted. Here we report a study of abortiveness of human and avian type A Influenza viruses in HeLa 229 cells in which the final stages of maturation of viral particles seem to be affected. We show that the incorrect insertion of virus-coded haemagglutinin into the plasma membrane might be the cause of the unpermissive condition of infection exhibited by this cellular host.

Animals

Effects of the heat-moisture exchangers on dynamic hyperinflation of mechanically ventilated COPD patients.

In recent years the use of devices called Heat and Moisture Exchangers (HME) has become widespread as gas conditioners for ICU patients requiring mechanical ventilation. As an important variation of the resistive properties of the HME, related to flow and duration of use, has recently been pointed out during "in vitro" studies, the use of these devices in COPD patients could increase the levels of auto PEEP and dynamic hyperinflation. In this study we have compared the levels of auto PEEP and difference in functional residual capacity (delta FRC) in a group of COPD patients, requiring controlled mechanical ventilation (CMV), at basal conditions and after the insertion into the circuit of three HMEs (Dar Hygrobac, Pall Ultipor, Engstrom Edith) at random: the results obtained excluded a significant increase of auto PEEP and delta (FRC) both with "new" HMEs and after 12 h of continuous use.

Aged

Auto-PEEP and dynamic hyperinflation in COPD patients during controlled mechanical ventilation and high frequency jet ventilation.

We investigated the levels of auto-PEEP and dynamic hyperinflation during high frequency jet ventilation (HFJV) and controlled mechanical ventilation (CMV) in six patients with chronic obstructive pulmonary disease within the first 36 h of acute exacerbation. The comparative evaluation was performed at similar conditions of gas exchange in HFJV and CMV: PaO2 77.6 +/- 11 mmHg vs 80.8 +/- 12 mmHg; PaCO2 46.8 +/- 2.5 mmHg vs 47 +/- 2.8 mmHg; pH 7.38 vs 7.38. In this situation, the values of auto-PEEP and dynamic hyperinflation, expressed as delta over the apneic functional residual capacity (FRC) did not differ: (auto-PEEPHFJV 8.9 +/- 3.8 cmH2O; auto-PEEPCMV 8.8 +/- 4.7 cmH2O; delta FRCHFJV 0.56 +/- 0.19 l; delta FRCCMV 0.54 +/- 0.2 l). This result suggests that, with a suitable machine setting and similar gas exchanges, HFJV produces the same level of auto-PEEP and dynamic hyperinflation as CMV in patients with chronic obstructive pulmonary disease.

Aged

Abortive replication of influenza A viruses in HeLa 229 cells.

Several experimental data support the idea that certain mammalian cells are unable to replicate influenza viruses type A, although these viruses can efficiently penetrate the cells. This cannot be attributed to a lack of specific receptors on the cell surface, but depends upon the failure of specific step(s) to occur during viral growth. Here we report a study of abortiveness of human and avian type A influenza viruses in HeLa 229 cells. Viral polypeptide synthesis was monitored by [35S]methionine pulse labelling at several time points after infection, showing that normal amounts of virus-induced components were synthesized. Cellular fractionation of HeLa 229 cells infected by influenza viruses showed that the distribution of viral proteins into nuclear and cytoplasmic compartments was comparable to that seen in the permissive host, chick embryo fibroblasts. Viral HA glycoprotein, produced during the infectious cycle, was entirely found in the cytoplasm of infected HeLa 229 cells. The polypeptide was able to agglutinate red blood cells but did not show positive haemadsorption even at late times of infection. Therefore it seems that during the maturation of viral particles there is a failure of the haemagglutinin to perform a correct insertion into the plasma membrane of infected HeLa 229 cells.

Animals

Chloroacetaldehyde is a powerful inducer of mitotic aneuploidy in Aspergillus nidulans.

The vinyl chloride metabolite chloroacetaldehyde (CAA) was tested for the induction of mitotic chromosome malsegregation in Aspergillus nidulans. Exposure of germinating conidia to CAA (16-64 microM) produced high rates of abnormal colonies with segregation of the whole first chromosome in the diploid strain P1, and abnormal, putative hyperploids in the haploid strain 35, indicating that CAA primarily induces abnormal chromosome segregation. Comparative assays with the known spindle poison chloral hydrate (CH), active in the dose range 6-10 mM, highlighted the unusual effectiveness of CAA in aneuploidy induction (the lowest effective concentration was 16 microM). Experiments on brain tubulin polymerization revealed an inhibitory effect by CAA only at concentrations 100-fold higher than those active in the induction of chromosome misdistribution in A. nidulans, possibly suggesting the involvement of alternative targets in its mechanism of action.

Acetaldehyde