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Biomedical subjects

G C Rossi

Publications and source records attributed to G C Rossi.

44 records · Page 3Linked to original sources
PubMed1995

How much are homologous peptides homologous?

A statistical analysis designed to deal with the problem of identifying homologous pairs of "short sequences of amino-acids" (= peptides) belonging to different proteins is presented. The conceptual novelty of the searching strategy proposed here lies in the fact that both the degree of homology of the two peptides of the pair (measured by a suitably defined affinity score) and the level of statistical significance of its occurrence are taken into account on equal footing. They are combined in a sort of "biological indicator", characterising each pair. Pairs for which the value of the biological indicator is larger than an appropriate threshold are taken as statistically significant and (putatively) biologically relevant. The method is employed in various test cases and proves to be reliable and efficient. In particular we have studied the cases in which the known existence of an auto-immune response has lead to the identification of homologous peptide pairs between human and viral or bacterial proteins. The detection efficiency of the algorithm in these cases turns out to be especially good when the most naïve affinity table, the Identity matrix, is employed to measure the similarity of amino acidic pairs. In contrast, when the 250-PAM mutation matrix is used, the detection efficiency goes to zero.

Algorithms↗
PubMed1995

Antisense mapping the MOR-1 opioid receptor: evidence for alternative splicing and a novel morphine-6 beta-glucuronide receptor.

Although MOR-1 encodes a mu opioid receptor, its relationship to the pharmacologically defined mu receptor subtypes has been unclear. Antisense mapping now suggests that these subtypes result from alternative splicing of MOR-1. Three oligodeoxynucleotide probes targeting exon 1 and another oligodeoxynucleotide directed against the coding region of exon 4 block supraspinal morphine analgesia, a mu1 action, while five of six oligodeoxynucleotides directed against exons 2 and 3 are inactive. Inhibition of gastrointestinal transit and spinal morphine analgesia, two mu2 actions, are blocked only by the probe against exon 4 and not by those directed against exon 1. In contrast, the analgesic actions of the extraordinarily potent mu drug morphine-6 beta-glucuronide are blocked by six different antisense oligodeoxynucleotides targeting exons 2 and 3, but not by those acting on exons 1 or 4. These results suggest that the mu1 and mu2 receptor subtypes originally defined in binding and pharmacological studies result from alternative splicing of MOR-1 while morphine-6 beta-glucuronide acts through a novel, previously unidentified receptor which is yet another MOR-1 splice variant.

Alternative Splicing↗
PubMed1994

Mu and delta opioid synergy between the periaqueductal gray and the rostro-ventral medulla.

Microinjection of [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO) into either the periaqueductal gray (PAG) or the rostral ventral medulla (RVM) elicits analgesia in the tailflick assay in the rat. Co-administration of DAMGO into both regions together results in a profound synergistic interaction similar to that we previously reported with morphine. U50,488H and DPDPE are inactive when given into either region. [D-Ala2,Glu4]Deltorphin (deltorphin), on the other hand, elicits an analgesic response, although the maximal response is less than than mu agonists. Co-administration of DAMGO into one region with deltorphin in the other also results in a significant synergy. However, co-administration of DAMGO and deltorphin together in the same region gives only additive effects. These results confirm the existence of mu/mu synergy between the PAG and RVM. kappa 1 and delta 1 agents are inactive, but the delta 2 agonist deltorphin is active in both regions. Our results indicate the presence of mu/delta 2 synergy between the PAG and RVM which appears to involve interactions of pathways rather than receptor interactions at the cellular level.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1994

[Efficiency of utilization of resources used at a polyvalent intensive care and resuscitation center].

Along the lunes of a survey by GIRTI of 2,710 patients hospitalized in the 14 costituing CRTI, a parallel research has been carried out 350 patients in a polyvalent CRTI in order to compare the results. Omega score has been calculated to evaluate the intensity of the supplied treatment and consequently to settle efficiency of the resources. The results show a greater number of treated patients compared to those only monitored for intensive examination and a majority of patients from medical and surgical departments, compared to those from traumatological dpts. This proves that the intensity of treatment depends significantly and progressively on the diagnosis, seriousness and, above all, duration of hospitalization, with the only difference that more resources were needed for those patients who died than for those survived. Despite the coincidence of the quality of the results, this survey diverges from that of GIRTI as far as the quantity of utilized resources, which were about a half of those reported in their survey. This is probably due to the lack of medical and particularly nursing personnel as well as instruments especially monitoring ones, which prevented CRTI from working at its maximum. Then it has been pointed out that some pathologies (extrahospital cardiac arrest and pulmonary embolism) which caused losses of the utilized resources, could improve by creating Emergency and Urgency Departments.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

An improved method for detection of words with unusual occurrence frequency in nucleotide sequences.

A statistical analysis designed to deal with the problem of identifying rare or abundant "words" of arbitrary length in genomic fragments is presented. Our approach has the novelty of taking into account the statistical role of the presence of shorter words nested into longer ones and of introducing a Bayesian correction to minimize the effects of statistical fluctuations and of possible mistakes in genomic data. The method is successfully used in a thorough analysis of the abundance of short nucleotide sequences in the Escherichia coli genome.

Base Sequence↗
PubMed1993

Medullary mu and delta opioid receptors modulate mesencephalic morphine analgesia in rats.

Supraspinal opioid analgesia is mediated in part by connections between the midbrain periaqueductal gray (PAG) and rostral ventral medulla (RVM) which includes the nuclei raphe magnus and reticularis gigantocellularis. Serotonergic 5HT2 and 5HT3 receptor subtypes appear to participate in this pathway since general and selective serotonergic antagonists microinjected into the RVM significantly reduced morphine analgesia elicited from the PAG. Since both an enkephalinergic pathway between the PAG and RVM and intrinsic enkephalinergic cells in the RVM exist, the present study evaluated the abilities of general (naltrexone), mu-selective (beta-funaltrexamine: B-FNA) and delta 2-selective (naltrindole) opioid receptor subtype antagonists microinjected into the RVM to alter morphine (2.5 micrograms) analgesia elicited from the PAG as measured by the tail-flick and jump tests. Mesencephalic morphine analgesia was significantly reduced after pretreatment in the RVM with naltrexone (1-10 micrograms), B-FNA (0.5-5 micrograms) or naltrindole (0.5-5 micrograms). Naltrexone in the RVM failed to alter basal nociceptive thresholds and none of the opioid antagonists were effective in reducing mesencephalic morphine analgesia when they were microinjected into placements lateral or dorsal to the RVM. These data indicate that mu and delta 2 opioid receptors in the RVM modulate the transmission of opioid pain-inhibitory signals from the PAG.

Analgesics↗
PubMed1993

Synergistic brainstem interactions for morphine analgesia.

Morphine is a potent analgesic when microinjected into the periaqueductal gray (PAG), the rostral ventral medulla (RVM) which contains the nuclei raphe magnus and reticularis gigantocellularis and the dorsolateral pons (DLP) which includes the locus coeruleus. Coadministration of low morphine doses which are inactive alone into combinations of these three regions elicits dramatic analgesic responses, implying the existence of synergy. The most effective combination is the PAG/RVM, whereas the PAG/DLP and RVM/DLP combinations are much less efficacious. In addition to fixed combinations, inclusion of a low morphine dose in one region shifts the analgesic dose-response curves in the others. The marked synergy between the PAG and the RVM is sensitive to naloxonazine, implying a role for mu 1 receptors. Thus, these studies indicate the presence of intrinsic brainstem mu 1 receptor systems with synergistic interactions which can be pharmacologically distinguished from the brainstem mu 2 receptors mediating supraspinal/spinal synergy.

Analgesics↗