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Biomedical subjects

G Conti

Publications and source records attributed to G Conti.

At least 91 records · Page 5Linked to original sources

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

Effects of L-carnitine administration on mitochondrial electron transport activity present in human muscle during circulatory shock.

Carnitine was administered to a group of patients in shock, and the activities of cytochrome oxidase and succinate cytochrome c reductase in muscle needle biopsies from these patients were compared to those activities present in a non-carnitine treated control group of patients. Carnitine seemingly exerted a significant protective action on cytochrome oxidase activity during the initial phases of shock, but not to such an extent on succinate cytochrome c reductase activities.

Carnitine

Effects of medroxyprogesterone acetate on DMBA-induced mammary tumors.

Rats with DMBA-induced mammary tumors were treated for 30 days i.m. with medroxyprogesterone acetate (MPA) at doses of 7.5, 15 or 75 mg/kg. Complete regression (disappearance of tumor) was observed in 60% and 20% of tumors from rats treated with 75 or 15 mg/kg MPA respectively. Partial regression (50% decrease in tumor area) was found in the remaining 20% of tumors from rats treated with 15 mg/kg MPA. The dose of 7.5 mg/kg MPA resulted in being devoid of effectiveness. Estrogen receptor (ER) levels were significantly reduced at all doses of MPA injected both in responsive and non-responsive tumors. However, only tumors with ER levels above 15 fmol/mg before therapy resulted in being responsive to MPA treatment. Progesterone receptors were so reduced at the end of the experiment as to not be detectable in all treated groups. It was concluded that MPA is effective as an antitumoral drug also in DMBA-induced mammary tumors and that this effect is at least in part related to ER levels before treatment.

9,10-Dimethyl-1,2-benzanthracene

Biological characterization of FPV, Ulster 73, replicative cycle.

The replication of an avian influenza A, Fowl plague virus (FPV), Ulster 73 strain, was studied in chick embryo fibroblasts, assumed to be the natural host, and in cells of different origin such as LLC-MK2, Hep-2, Vero, KB and Mc Coy. In the natural host, FPV shows a characteristic pattern of polypeptide synthesis suggesting a transcriptional and/or translational mediated control mechanism, specific for this strain of influenza A. FPV was able to give a productive infection in all the above mentioned cells releasing mature viral particles. This behaviour is very interesting if one compares FPV, Ulster strain to FPV, Rostock strain. These viruses, belonging to the same antigenic subtype (H7 N1 group) recognize the same cellular determinants but Rostock strain undergoes an abortive replication whereas Ulster strain gives productive infection in all cellular lines tested. These observations lead to postulate a viral genetic mechanism controlling host range both at early and late steps in infection. This genetic mechanism controls the interaction between viral and cell molecules affecting synthesis of virus specific polypeptides.

Animals

Induction of somatic segregation by halogenated aliphatic hydrocarbons in Aspergillus nidulans.

8 halogenated aliphatic hydrocarbons were assayed for their ability to induce somatic segregation in the mould Aspergillus nidulans. Induction of haploidization, mitotic non-disjunction and mitotic crossing-over was studied in heterozygous colonies exposed to the tested chemicals through the detection and phenotypic analysis of segregated sectors. The results obtained show that 1,2-dibromoethane induced all kinds of segregated sectors; 1,2-dichloroethane, allyl chloride, 2-chloroethanol, 2,2-dichloroethanol and 2,2-dichloroacetaldehyde significantly increased the frequency of haploid sectors and diploid non-disjunctional sectors; chloroform and 1,2-dichloropropane were ineffective.

Aspergillus nidulans

Effects of long-term administration of high doses of medroxyprogesterone acetate on hormone receptors and target organs in the female rat.

The changes in oestrogen, progesterone and prolactin receptor levels in target organs, and the macroscopic and microscopic modifications of uterus, ovary, adrenal and pituitary gland induced by long-term administration of high doses of medroxyprogesterone acetate (MPA) were investigated in female rats. Medroxyprogesterone acetate was injected i.m. for 30 days at daily doses of 7.5, 15 and 75 mg/kg. Oestrogen and/or progesterone-binding capacities were remarkably reduced at all doses of MPA used both in the uterus and pituitary gland. Furthermore, MPA caused a very evident reduction in the weight of pituitary glands, ovaries, adrenals and uterus. In all MPA-treated rats corpora lutea were absent from the ovaries, whereas the adrenals showed a significant reduction in the thickness of the cortex. In accordance with this, there was no evidence of ACTH-producing cells in the pituitary glands. Prolactin-producing cells were also absent, while GH-producing cells were present. Serum prolactin levels were significantly reduced at all doses of MPA used. A dramatic reduction of prolactin receptor concentrations was observed in the liver and the ovaries of MPA-treated rats. The results suggest that MPA acts as an antioestrogenic drug both by reducing the number of oestrogen receptors in target tissues and by changing the structure (and perhaps the function) of those organs (pituitary glands, ovaries and adrenals) which are, directly or indirectly, a source of oestrogens. The decreased synthesis of prolactin and the reduction of the number of prolactin receptors (which, on the contrary, are both increased by oestrogens) might be considered as additional antioestrogenic effects of MPA.

Adrenal Glands