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Biomedical subjects

G Conti

Publications and source records attributed to G Conti.

At least 73 records · Page 4Linked to original sources

Evaluation of the mutagenic activity of leucinostatins, a novel class of antibiotic peptides produced by Paecilomyces marquandii, in the modul Aspergillus nidulans.

Leucinostatins A, B, C, D, E, G, H, and K were thoroughly investigated for their genotoxic activity using the modul Aspergillus nidulans as the test organism. The results of assays for gene mutation (8-azaguanine resistance and methionine suppressors), gene conversion, mitotic crossing-over and mitotic aneuploidy induction suggest that these peptide antibiotics lack significant mutagenicity and that non-genotoxic mechanism(s) underlie their cytotoxic properties.

Anti-Bacterial Agents

Latency of the auditory brainstem response (ABR) and head size. Evidence of the relationship by means of radiographic data.

The role of head size to determine the inter-subject variability of the auditory brainstem response (ABR) was investigated in 32 normally hearing adults (19 females, 13 males, aged 18 to 52). The ABRs were evaluated in respect to the absolute latency of waves I, III and V and the interpeak latencies I-III, III-V and I-V. Plain films of the skull (3 views) were also taken of each subject and several measures were calculated in order to obtain an evaluation of the dimensions of both the most rostral parts of the skull and of the posterior fossa. The radiographic data as well as the ABR parameters showed significantly shorter values in females than in males. There was a strong positive correlation between the two variables when a linear regression procedure was applyed. The highest value of the correlation coefficient (r = 0.8) was found in the relationship between the wave V latency and the posterior fossa measures. High r values and similar factors in the regression equation were also found after considering the subjects separately according to sex. These results show that the ABR latencies linearly increase together with the skull size as it appears in the X-rays, regardless of the subject's sex. We can consequently deduce that the length of the neural pathway is the main factor of inter-sex variability of the response.

Adult

Clinical use of differential continuous positive airway pressure in the treatment of unilateral acute lung injury.

In some instances of unilateral acute lung injury (ALI) refractory to conventional ventilatory support, the intact lung is still able to ensure an efficient CO2 washout, the concomitant hypoxaemia being due to the loss of volume of the injured parenchyma. In these cases, the administration of a sufficient selective continuous distending pressure by means of differential continuous positive airway pressure may restore to normal the resting volume and thus the ventilatory performance of the affected lung, contemporarily avoiding the occurrence of pulmonary and systemic barotrauma.

Adult

Inhibitory effect of diamidinophenylindole on the replication of influenza virus in permissive cellular hosts. Brief report.

The production of avian and human strains of influenza virus was altered to various extents by treatment of various host cells with 40 micrograms/ml of diamidinophenylindole (DAPI). In infected LLC-MK 2 cells only an abortive replication cycle occurred; in other cell lines there was partial inhibition or no inhibition of replication. Virus polypeptide synthesis in LLC-MK 2 cells was confined to the early pattern of viral multiplication; only the P proteins, the nucleoprotein NP, and the non-structural protein NS 1 were synthesized. The stage of replication mainly affected by DAPI was between the fourth and the sixth hour after infection. The mode of action of the drug and its modulating effect on virus production is discussed.

Animals

On the mechanism of mitotic segregation induction in Aspergillus nidulans by benzene hydroxy metabolites.

The principal hydroxy-metabolites of benzene--hydroquinone, catechol and phenol--were assayed in tests for mitotic segregation induction in Aspergillus nidulans diploid strain 19. Hydroquinone was the most effective chemical, increasing the frequency of mitotic segregants up to 10-fold at 1-3 mM. Catechol was similarly active at 10-20 mM and phenol was weakly positive at 15 mM. Genetic characterization of induced abnormal segregating colonies by replating and complementary assays with haploid strain 35 suggest that gross chromosomal aberrations, instead of numerical abnormalities, are the primary genetic damages induced by hydroxybenzenes in A. nidulans. The protecting activity exerted by L-cysteine against equimolar concentrations of hydroquinone supports a free radical mechanism for hydroxybenzenes genotoxicity in A. nidulans.

Aspergillus nidulans

Modifications of the vein wall after microsurgical end-to-side artero-venous anastomosis.

The repercussions on the venous wall of the creation of 20 artero-venous anastomoses (AVA) between the femoral artery and vein of the rat have been evaluated. The rats were killed 7, 15, 30, and 90 days after AVA, and AVAs were examined by optical microscopy and by scanning electronic microscopy. Deposits of whitish material that nearly completely occluded the venous lumen were seen, especially in the group studied longer than 90 days. These venous wall lesions, which resemble arteriosclerotic lesions, must be attributed to the new hemodynamic situation created by the AVA. The implications of such findings for the long-term validity of venous graft in vascular microsurgery and the long-term patency of the AVA in hemodialyzed children are discussed.

Animals

Clinical applications of independent lung ventilation with unilateral high-frequency jet ventilation (ILV-UHFJV).

Six patients with unilateral acute lung injury (ALI) were treated with a new form of ventilatory support: independent lung ventilation with unilateral high-frequency jet ventilation (ILV-UHFJV). The first three patients suffered from unilateral ALI complicated by a bronchopleural fistula (BPF); they were at first ventilated with HFJV, but remained unresponsive to treatment, showing a progressive impairment of the ventilation/perfusion ratio with a deterioration in clinical condition. After selective bronchial intubation, ILV-UHFJV was started, ventilating the healthy lung with CPPV and the contralateral with HFJV. ILV-UHFJV caused a significant improvement in alveolar gas exchange leading to a rapid fall in Qs/Qt; it was also associated with a stable haemodynamic condition throughout the duration of the treatment. Subsequently, three more patients were treated; their respiratory failure was due to a unilateral ALI without BPF, unresponsive to either HFJV or CPPV. Once again, ILV-UHFJV was followed by a dramatic improvement in respiratory function; the haemodynamics remained unchanged and it was also possible to demonstrate a rapid improvement in individual and overall lung function.

Adult

A comparative study on selected chemical carcinogens for chromosome malsegregation, mitotic crossing-over and forward mutation induction in Aspergillus nidulans.

10 "false negative" chemical carcinogens, i.e. ineffective in bacterial mutagenicity assays, were thoroughly investigated for their genotoxic activity in the mould Aspergillus nidulans. Forward mutations (methionine suppressors), mitotic crossing-over and chromosome malsegregation were the end-points scored. Positive results were obtained in tests for the induction of mitotic segregation with benzene, ethylenethiourea and urethane, which increased the frequency of abnormal presumptive aneuploid colonies with euploid sectors showing whole chromosome segregation (i.e. non-disjunctional diploids and haploids). The same compounds were ineffective in increasing the frequency of mitotic crossing-over or forward mutations. The other chemical carcinogens investigated, namely acetamide, amitrole, dieldrin, heptachlor epoxide, nitrilotriacetic acid, p,p'-DDT and thiourea were ineffective both as inducers of forward mutations and mitotic segregation.

Aspergillus nidulans

[Clonogenic growth of tumor cells in vitro].

We expose here our first results concerning clonogenic growth of 40 cases of malignant tumor plated in semi-solid medium (methylcellulose). The growth is determined by the presence at day 21 of colonies (cellular group with more than 60 micron diameter). 26 cases were considered significant. A 61% growth has been observed with primary solid tumors, and 83.4% with ascites, ovarian carcinoma growing the best. Cellular viability, plating efficiency and when the cellular number allowed it, linear graphic curves have been established. An ultrastructural morphological study, illustrated here by 2 cases--one ovarian carcinoma and one colonic adenocarcinoma cell line--has shown that all colony 's cells belong to a same cellular type and present various degrees of differentiation, suggesting a possible analogy between our observations and the hypothetical tumor cell model, concerning human carcinoma's organisation and self renewal.

Cell Division

[Nitrendipine, a new calcium antagonist, in the therapy of arterial hypertension].

Bay e 5009 (nitrendipine) is a new calcium-antagonist that acts mainly on blood vessel smooth muscles. The effects of this drug on hypertensive patients of both sexes was investigated. Nine patients were treated for 42 days at a fixed dosage of 1 tablet/day. A highly significant fall in arterial pressure was obtained (p less than 0.001). Seven patients took 20 mg/day of nitrendipine for 14 days and a significant reduction in A.P. was obtained (p less than 0.001): for the next four weeks, the dosage was increased to 20 mg twice a day when a further decrease in systolic and diastolic A.P. was obtained without the occurrence of side effects. A further five patients were treated for 14 day (20 mg/day). These showed a fall in blood pressure levels (p less than 0.001) but suffered from slight oedema which made it necessary to suspend the treatment. An increase in heart rate was noted in all patients (p less than 0.001). This was due to reflex adrenergic activation. Nitrendipine therefore proved effective as an antihypertensive drug even at a daily dose of only 20 mg.

Adult

Estrogen and progesterone receptors in the human vagina.

Estrogen (E) and progesterone (Pg) receptor (R) levels were determined in the human vagina in relation to menopausal status, day of ovarian cycle and pregnancy. The results obtained confirmed that the human vagina contains ER and, in addition, demonstrated for the first time the presence of PgR in this organ in humans. In cycling women, ER and PgR did not vary significantly during the ovarian cycle; however low (less than or equal to 10 fmoles/mg cytosol protein) concentrations of PgR were more frequently (6 out of 8 cases) detected during the secretory phase. No substantial difference was seen in ER and PgR values between anterior and posterior wall of the vagina. In postmenopausal patients the levels of ER (range: 10-83 fmoles/mg) were similar to those found in premenopause (range: 12-78 fmoles/mg). As regards PgR, the majority (14 out of 20) of vaginae were devoid of PgR, 4 had a very low (less than or equal to 6 fmoles/mg) PgR content and only 2 cases had a PgR level higher than 10 fmol/mg cytosol protein. In pregnant patients (6th to 8th week) ER were found in all vaginae, while PgR were present only in some cases (3 out of 8). It was concluded that the behavior of ER in the human vagina seems different from that in the human endometrium, since ER levels do not vary in relation to changes in the concentrations of sexual hormones in the circulation. On the contrary, PgR levels appear to depend on blood estradiol and progesterone concentration, as in other target tissues.

Adult

Mutagenicity of trichloroethylene, trichloroethanol and chloral hydrate in Aspergillus nidulans.

A trichloroethylene (TCE) sample, free of epoxides, has been assayed for its ability to induce gene mutations (methionine suppressors) and mitotic segregation in the mould Aspergillus nidulans. No increase in the spontaneous frequency of methionine suppressors was observed when conidia of a haploid strain were plated on selective medium and exposed to TCE vapours. A weak but statistically significant increase in methionine suppressors was detected, however, when conidia of cultures grown and conidiated in the presence of TCE vapours were plated onto selective media. Growing colonies of a heterozygous diploid strain were exposed to TCE vapours to investigate the induction of mitotic segregation. Scoring and phenotypic analysis of segregant sectors showed a significant increase in the frequency of haploids and 'non-disjunctional' diploids but not of cross-overs. Treatment of quiescent conidia in liquid medium was ineffective. Trichloroethanol and chloral hydrate, two main TCE metabolites in mammals, shared the ability to induce somatic segregation demonstrated by TCE vapours. On the grounds of these results the possible endogenous metabolic conversion of TCE into trichloroethanol and chloral hydrate is hypothesized.

Aspergillus nidulans