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Biomedical subjects

G Conti

Publications and source records attributed to G Conti.

At least 145 records · Page 8Linked to original sources

Effect of coumermycin on influenza A virus replicative cycle.

Coumermycin A1, a Novobiocin related antibiotic, has been tested in vivo and in vitro for its activity on Influenza A viruses. In a range of concentrations between 3 and 5 micrograms/ml virus production was drastically reduced. The drug was able to inhibit virus release into culture medium also if added up to the sixth hour following infection and its action was reversible within this time. The synthesis of virus induced polypeptides was generally depressed but production of the HA was more deeply inhibited. Viral transcriptase activity in vitro was also affected by the presence of Coumermycin A1 but at doses which seem to high to consider this event as a phenomenon likely to play a role in vivo. It is suggested that the antiviral activity of the drug is mediated by the inhibition of the host cell metabolism.

Aminocoumarins

Effects of bromocriptine and dopamine on the binding of estradiol to its uterine cytoplasmic receptors.

The in vivo and in vitro effects of bromocriptine on the binding of estradiol 17 beta to its specific uterine receptors were studied in both mature and immature rats. A single i.p. injection of bromocriptine reduced the specific estradiol-receptor interaction in adult rats, while it resulted ineffective in prepubertal animals. The effect of bromocriptine in mature rats was dose-dependent and evident only when using a dose of at least 0.70 mg/kg. Experiments in vitro also showed that in mature rats bromocriptine affected the estradiol-receptor interaction inducing a decrease in binding, which is well correlated to the concentration used. On the contrary, no effect of bromocriptine in vitro was observed when using cytosol obtained from uteri of immature rats. Very similar results were obtained in experiments in vitro when using dopamine instead of bromocriptine. Our results suggest that apparently there are two forms of estrogen receptors, one present both in prepubertal and pubertal age and the other present only in mature animals. The latter is the type of receptor sensitive to both bromocriptine and dopamine and presumably develops under the control of hormonal factors, which are only present at puberty.

Animals

Electrocochleography and brainstem potentials in the diagnosis of the deaf child.

The deaf child must receive sound amplification before he reaches the age of two years. At this age the hearing threshold is best measured objectively by electrocochleography (ECochG) and auditory brainstem response (ABR) audiometry. When used correctly, both methods allow an exact threshold estimation which is informative enough for adequate hearing aid prescription. Both methods have advantages and disadvantages when used in children. The advantages of ECochG are: (a) a more exact threshold estimation and (b) strictly monaural evaluation. The advantages of ABR are: (a) ease of performance; it is not invasive and does not require general anaesthesia and (b) allows for exploration of higher levels in the auditory pathway up to the midbrain. We believe that ECochG and ABR are compatible and complementary in the diagnosis of childhood deafness. ABR could be used in first instance, while ECochG could be reserved for doubtful cases and for those who cannot be adequately sedated. Extra-audiological factors such as the availability of anaesthetists and varying hospital facilities, play a further role in determining the choice of electric response technique.

Audiometry

Changes in the binding of oestradiol to uterine oestrogen receptors induced by some progesterone and 19-nor-testosterone derivatives.

The effects of two progesterone derivatives, namely medroxyprogesterone acetate (MPA) and chlormadinone, and two 19-nor-testosterone derivatives, namely norgestrel and norethisterone, on the binding of oestradiol to its cytoplasmic receptors in the rat uterus were compared. In experiments performed in vivo, the rats were given a single oral dose (15 mg/kg) of one of the four progestins and killed 1, 6, 24 and 48 h later. Norgestrel, norethisterone and MPA induced a prompt and remarkable decrease in oestradiol-receptor interaction 1 h after treatment. This reduction lasted almost unchanged for 24 h in rats treated with MPA or norgestrel, but was much lower in animals given norethisterone. In the hours that followed, the effect of MPA and norgestrel began to decrease, but was still detectable after 48 h, whereas the effect of norethisterone had disappeared by this time. The effect of chlormadinone was much less than that induced by both MPA and norgestrel 1, 6 and 24 h after treatment. On the other hand, this effect was less than that caused by norethisterone 1 h after administration, equal after 6 h and much greater after 24 and 48 h. In experiments performed in vitro, the different ability of the four progestins to interfere with the capacity of oestradiol to bind to its receptors was confirmed. In conclusion, all the synthetic progestins used were able to reduce the binding of oestradiol to its cytoplasmic receptors, although there was a clear difference between the progestins in the intensity and duration of this effect. This could be one of the mechanisms by which progestins modulate the activity of oestrogens in target tissues.

Animals

Evaluation of the monaurally evoked brainstem response in the diagnosis of sensorineural hearing loss.

The auditory brainstem responses (ABRs) obtained in 47 subjects with asymmetric hearing loss (12 with surgically confirmed cerebello-pontine angle tumours, 35 without otoneurologic and/or neuroradiologic evidence of tumour) were evaluated by means of an index named delta V. The calculation of this index was based upon the patient's wave V absolute latency obtained at a fixed intensity of 90 dB HL and the value of latency predictable by means of the normative data. The index clearly separates retrocochlear from cochlear sites of lesion. Moreover delta V values obtained in defined cochlear lesions show a linear relation with the patient's pure tone hearing loss at 2 and 4 kHz; this behaviour is probably due to a reduction of the auditory dynamic range in the recruiting ears. delta V appears to have clinical usefulness because of two main points: first it is based upon an evaluation of the monaurally evoked ABR; second, it improves the diagnostic specificity of the responses. The rate of false positive results can be further reduced by combining delta V and IT5 values.

Audiometry, Evoked Response

Metastatic potential of metastases, tumor cell heterogeneity, and therapeutic implications.

The metastasizing capacity of spontaneous metastases of several murine tumors of different histology, origin, and disseminative pattern was investigated to test the hypothesis that metastases originate from various subpopulations within the primary tumor. Overall, tumor cells from individual metastases did not show greater metastasizing capacity than the cells of the original tumor, although a degree of heterogeneity was seen. Differences in the immunologic profile among metastases of the same tumor were also observed. The possible therapeutic implications of these findings are discussed.

Animals

Evaluation of 2 different genetic markers for the detection of frameshift and missense mutagens in A. nidulans.

21 chemicals, known to induce missense and/or frameshift mutations directly, were assayed for their ability to forward mutate a haploid strain of A. nidulans. 2 genetic markers for forward mutations were used, namely 8-azaguanine resistance and induction of meth A1 suppressors. Missense mutagens were usually active when tested with the plate-incorporation technique, whereas frameshift agents were ineffective; some of these, on the other hand, turned out to be positive when tested with a liquid-test procedure. The 2 genetic markers used showed a similar sensitivity (with only 2 exceptions) in detecting the chemical mutagens assayed.

Aspergillus nidulans

[The sigma sedimentation rate in rheumatoid arthritis: comparative study of the erythrocyte sedimentation rate].

The authors studied 54 patients suffering from rheumatoid arthritis by sigma SR method. The sigma SR, unlike the ESR, often reveals inflammatory activity in patients suffering from possible or probable rheumatoid arthritis and is very useful to diagnose the disease. The sigma SR constantly increases when the disease is in active period, unlike the ESR, in patients affected by classic or definite rheumatoid arthritis. The authors conclude the sigma SR determination is useful in every case of rheumatoid arthritis, especially when the disease is at beginning and is difficult to be diagnosed, i.e. cases of possible and probable rheumatoid arthritis, and when clinical and biohumoral picture disagree.

Arthritis, Rheumatoid

Growth-mediated metabolic activation of promutagens in Aspergillus nidulans.

7 procarcinogens belonging to different chemical classes (nitrosamines, hydrazoalkanes, oxazaphosphorines and aromatic amines) were tested in A. nidulans for the induction of point mutations with two genetic systems (8-AG resistance and induction of methionine suppressors). Dimethylnitrosamine, diethylnitrosamine, nitrosomorpholine, dimethylhydrazine, procarbazine and cyclophosphamide gave positive results with a good dose--effect relationship in the growth-mediated assay, whereas they gave negative or borderline positive results in the plate incorporation assay. 2-Aminoanthracene was completely negative with both experimental procedures. DMN, DEN and NM were also tested for their ability to induce somatic segregation: all were positive when assayed in the growth-mediated assay.

Amines

Different patterns of replication in influenza virus-infected KB cells.

When KB cells were infected either with the fowl plague (FPV) Rostock strain (Hav1N1) or the WSN (H0N1) strain of influenza A virus the yield of cell-associated haemagglutinin and neuraminidase polypeptides was essentially comparable, but virus particles were not produced in the FPV-KB system. WSN virus-infected KB cells synthesized normal amounts of mature virus particles and had all the characteristics of a permissive replication cycle. Biosynthesis and transport of RNP antigen from nucleus to cytoplasm of infected cells were traced by immunofluorescent staining at 4 and 8 hours after the beginning of infection. While the fluorescent-stained material was totally confined to the nuclei in FPV-infected KB cells, RNP antigen migrated out of the nucleus during the replicative cycle of WSN virus in the same host cell. Patterns of virus-specific protein synthesis were studied by pulse-labelling with 35S-methionine. The most significant feature concerned the amplification of synthesis of virus-induced matrix (M) protein which did not occur in FPV-infected cells but occurred normally during WSN infection. The different patterns of replication in the same host cell when infected by different influenza A viruses is discussed.

Cell Line

Mutagenicity of halogenated aliphatic hydrocarbons in Salmonella typhimurium, Streptomyces coelicolor and Aspergillus nidulans.

Eight structurally related halogenated aliphatic hydrocarbons mono-, di- and trichloroacetaldehyde (the last in the anhydrous and hydrate form), moni-, di- and trichloroethanol and allyl chloride, were tested for their ability to induce gene mutations in prokaryotic and eukaryotic microorganisms. The genetic systems employed were the Salmonella reversion test with strain TA1535 and TA100, with and without metabolic activation, a forward and a back-mutation system in S. coelicolor and two forward mutation systems in A. nidulans. Each compound was tested with the spot and plate incorporation assay techniques. Mono-, di- and trichloroacetaldehyde were mutagenic in all the microorganisms employed; all the halogenated ethanols were positive in A. nidulans, while in S. typhimurium and in S. coelicolor the only active forms were respectively the mono- and dichloroderivatives. Allyl chloride was active in S. typhimurium and S. coelicolor and negative in A. nidulans. The technical approach as well as the complex influence of different factors (toxicity, volatility and stability) on the genetic response of each of the compounds under test did not allow to obtain more than a qualitative relationship between mutagenic potency and chemical structure.

Animals