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Biomedical subjects

L Bossi

Publications and source records attributed to L Bossi.

At least 19 recordsLinked to original sources
PubMed1991

Common sequence determinants of the response of a prokaryotic promoter to DNA bending and supercoiling.

Inhibiting the activity of DNA gyrase by mutation or by drugs in S. typhimurium causes the loss of transcription attenuation in the histidine operon. We show that gyrase activity is needed to maintain high-level expression of the tRNA(His) gene (hisR), a prerequisite for proper functioning of the attenuation mechanism. A point mutation in the promoter of the tRNA gene cluster which includes the hisR gene, specifically relieves the promoter response to negative supercoiling thereby restoring full hisR transcription (and, in turn, his attenuation) in the presence of a defective gyrase. The very same mutation, a single base-pair substitution between the -10 box and the transcription start site (-7), was found independently among suppressors of the transcriptional deficiency caused by disruption of DNA curvature upstream from the hisR promoter. We show that the -7 change does not lead to a generalized increase of promoter strength; the effects of the mutation are seen only when gyrase is inhibited or the upstream curvature is altered. This suggests that the upstream curvature intervenes in the same initiation step which is sensitive to superhelical tension. Three additional promoter mutations correcting (or alleviating) the effects of the upstream alteration (including a change at -8) are described and discussed.

Base Sequence↗
PubMed1990

[Diagnostic and therapeutic of human hydatidosis. Study of a hospital case series].

A case-study on 95 inpatients with hydatid disease admitted to a community hospital in Milan is presented. Clinical records from January 1975 through December 1985 were reviewed. Data were analyzed according to: individual characteristics of the subject; previous history of hydatid disease and present signs and symptoms; tests and instrumental examinations performed to ascertain the disease; type of treatment and outcome. Liver (56%) and lung (18%) were the most commonly involved organs, but lung location was, relatively to age, more frequent in children and teenagers than in adults. Intradermal (Casoni) or serological (Ghedini) tests and scintigraphy for the hepatic localization, and lung stratigraphy or histologic section for the pulmonary one, were the most frequent examinations performed. Seventy-three patients (77%) underwent surgical treatment.

Adolescent↗
PubMed1989

[Acute and chronic cerebrovascular diseases. A therapeutic approach].

The effectiveness of a specific treatment for ictus in its acute phase is highly controversial. A series of variables is identified in 1503 cases that would appear to have a particular effect on the reduction of mortality. On these, specific treatment with Buflomedil coincides with a reduction in lethal outcome of 4% over the two-year period out of 380 cases. In their turn chronic postictal and cerebral ischaemia states (a total of 105 cases) respond positively to prolonged treatment with Buflomedil in a percentage varying from 57% in postictal chronic states to 70-73% in chronic cerebral ischemias.

Brain↗
PubMed1988

Transcription induces gyration of the DNA template in Escherichia coli.

We show that transcription modulation of a plasmid sequence in exponentially growing Escherichia coli cells leads to a rapid change in the linking number of plasmid DNA. Activation of transcription is accompanied by an increase in the plasmid's level of negative supercoiling. The added superhelical turns, whose number is proportional to the strength of the promoter and to the length of the transcript, are promptly removed when transcription is turned off. The transcription-induced increase of template supercoiling can still be detected in the presence of an inhibitor of ATP-dependent DNA gyrase [DNA topoisomerase (ATP-hydrolyzing), EC 5.99.1.3]. Altogether, our results indicate that, in addition to being under a general control, DNA superhelicity can be modulated locally in response to the topological perturbations associated with DNA tracking processes. We discuss a model in which supercoiling changes are produced by differential swiveling activities on the opposite sides of a transcriptional flow during transcriptional modulation.

DNA Topoisomerases, Type II↗
PubMed1986

Alterations of GABA-mediated synaptic transmission in human epilepsy.

Although animal models consistently indicate that gamma-amino-butyric acid (GABA) synaptic function (GABA levels, synthesis, uptake and/or receptors) is decreased in seizure states, there is little evidence to date in support of such a hypothesis for human epilepsy. This chapter presents the results of an in-depth study of the activity of the GABA-synthesizing enzyme L-glutamic acid decarboxylase (GAD) in brain tissue removed during neurosurgical resection for intractable epilepsy. The tissue studied is unique in that identified (by stereo EEG) foci were excised (rather than large blocks of tissue containing mixtures of foci and nonepileptic material) and compared with nonepileptic (stereo EEG and morphological definitions) tissue from the same patients. In patients in which there was no indication of a tumor, GAD activity in the foci was low in more than 50% of the patients examined. Furthermore, when the population distribution of GAD was compared in epileptic versus nonepileptic tissue fragments from all patients, the peak distribution of epileptic tissue fragments occurred at much lower GAD activities than for the nonepileptic fragments (0-20 versus 41-80 nmol CO2/mg protein X hr, respectively). A small subgroup of epileptic fragments occurred with a normal GAD distribution, indicating that the presence of an epileptic focus was not invariably associated with low GAD activity. When the low levels of GABA "A" binding sites in these epileptic tissue fragments are taken into consideration in combination with the low GAD levels, then it can be estimated that 60 to 70% of the present patient population had deficient GABAergic transmission in epileptic foci as compared to nonepileptic brain tissue from the same patients. It follows that the GABA hypothesis of human epilepsy is not an exclusive or unitary hypothesis, and some patients appear to have normally functioning GABA synapses (as assessed biochemically) in epileptogenic areas. Thus, other neurotransmitter and neurohumoral systems certainly play a role in the epileptic process.

Animals↗
PubMed1985

[Stroke and post-ictal states].

Strokes and their sequelae are currently a major medical and social problem. Hence prevention is fundamental. The treatment of evident stroke whether general therapy, target treatment of the cerebral oedema, or specific treatment of the cerebral haemorrhage or thromboembolism is therefore equally important, though subject to controversy. In a case series of 1015 strokes, paramedical assistance and early physiokinesitherapy proved decisive. Specific treatment of the ischaemia using Buflomedil together with computerised EEG monitoring also looks promising.

Brain Edema↗
PubMed1985

[Buflomedil and nicergoline in the targeted treatment of acute cerebral ischemia. Randomized comparative double blind study].

Acute cerebral ischaemia may take considerable advantages of an adequate intensive therapy associated with a specific treatment of cerebral oedemas, especially in terms of mortality-rate reduction. Moreover, target treatment of acute cerebral ischaemia may produce excellent results in severe cases selected by means of EEG-chronospectrography. Double-blind, randomized comparison between nicergolin and buflomedil especialls showed that the latter reduces mortality three times as much as nicergolin, and leads to a 200% increment in the complete recovery of the "functio laesa", limited to those cases, which showed an appreciable improvement following EEG-chronospectrographical survey.

Acute Disease↗
PubMed1985

Clinical activity of GABA agonists in neuroleptic- and L-dopa-induced dyskinesia.

It is well known that the therapeutic effect of neuroleptics is counterbalanced by the property of these drugs to induce serious neurological side-effects mainly represented by tardive dyskinesia. Several reports indicate that at the experimental level GABA agonists interact with dopamine neurons with effects on behavior, stereotyped and dyskinetic movements induced by either lesions or dopamine agonists. This action on dopamine-related events provides a basis for a possible therapeutic action of GABA agonists in dyskinesia. Previous results with the GABA agonists muscimol and THIP in tardive dyskinesia have not been encouraging. The present paper deals with clinical results obtained with the new GABA agonist progabide both in neuroleptic-induced dyskinesia and in L-dopa-induced dyskinesia from five studies conducted on a total of 57 patients. Twenty-nine patients suffering from neuroleptic-induced dyskinesia have been treated in three studies (two open, one double-blind cross over) with progabide at doses from 900 to 2400 mg/day; clinical evaluation and EMG testing are in favor of a therapeutic effect of progabide on dyskinesia. Twenty-eight patients with L-dopa dyskinesia have been studied in two double blind trials. At variance with studies in tardive dyskinesia progabide was not effective in this kind of dyskinesia but an increase in the "on" time has been observed in both studies. Attempts to treat tardive dyskinesia with various pharmacological tools are reviewed and discussed, showing that at present no established effective treatment exists for this frequent complication of neuroleptic use. The possible mechanism of action of progabide in dyskinesia is discussed in the light of its pharmacological properties. These results suggest that progabide can be useful in the treatment of neuroleptic-induced dyskinesia.

Antipsychotic Agents↗
PubMed1978

Characterization of a Salmonella typhimurium hisU mutant defective in tRNA precursor processing.

The DA11 mutant of Salmonella typhimurium, originally isolated as derepressed for the histidine operon, carries a temperature-dependent alteration in a nucleolytic enzyme specifically involved in the maturation of tRNA. As a consequence of this alteration, no detectable synthesis of any mature tRNA species occurs in DA11 upon shift at 43 degrees C, whereas many tRNA precursors, whose sizes range between 80 and 750 nucleotides, do accumulate. Kinetic studies on the synthesis and processing of these maturation intermediates show that these molecules represent different stages in the maturation pathway, most of them being the products of previous nucleolytic events. These RNA molecules are in vivo substrates of methylation and thiolation enzymes and can be cleaved in vitro to 4S RNA by wild-type but not by DA11 cell-free extract. Evidence is presented that DA11 is very probably a ribonuclease P mutant.

Histidine↗
PubMed1977

Biosynthesis of tRNA in histidine regulatory mutants of Salmonella typhimurium.

HisU mutants of Salmonella typhimurium are depressed in the histidine operon since they have lower intracellular concentration of histidyl-tRNAHis. In this paper we present evidences showing that a strain carrying a hisU mutation (hisUl206) is altered in a nucleolytic enzyme involved in tRNA maturation process. The analysis of several hisU mutants indicates that hisU region of bacterial genome may account for more than one function involved in tRNA biosynthesis.

Histidine↗
PubMed1977

Carbamazepine and carbamazepine-10, 11-epoxide concentrations in human brain.

1 Carbamazepine (CBZ) brain and plasma concentrations were measured in twenty-one patients undergoing brain surgery for tumour removal. The drug was administered prophylactically at doses ranging from 6.9 to 14.8 mg/kg for 4-5 days before the intervention. 2 In seventeen cases where sample were collected 10-14 h after dosing, CBZ brain levels ranged from 2.2-14.5 microgram/g. A significant linear relationship (p less than 0.01) was observed between brain and plasma concentrations with a brain/plasma ratio of 1.1 +/- 0.1. 3 Carbamazepine 10,11-epoxide (CBZ-Epox), present in all samples, could be quantified in three brain specimens. Its brain concentrations ranged from 1.5-2.7 microgram/g with a brain/plasma ratio of 1.1-1.2. 4 Parieto-occipital areas tended to show higher CBZ concentrations while lower values were found in temporal regions. Very low CBZ levels were found in two gliomas while in meningiomas CBZ levels were similar to those observed in normal tissue. 5 The data, showing a linear relationship between brain and plasma concentrations of both CBZ and its epoxide, give additional significance to the plasma level monitoring of antiepileptic drugs.

Adult↗
PubMed1977

Plasma levels of di-no-propylacetate and clonazepam in epileptic patients.

Plasma levels of DPA and CNP and associated antiepileptic drugs were measured in groups of respectively 106 and 30 epileptic patients aged from 3 to 49 years. A poor correlation between daily oral dose and plasma levels of both drug was observed when the whole group of patients was considered. A better correlation was seen in a group of adult patients who received DPA and PB. Children below 10 years of age disposed both drugs faster than adults and the difference was significant (p less than 0.01) in groups receiving PB as associated drug. Patients medicated with PB and DPA or CNP showed lower plasma levels of both drugs; on the other hand DPA appeared to cause a decrease of PB clearance which was more marked in children. The clinical significance of the fluctuations of daily plasma levels of both drugs are discussed in relationship to the schedule of administration and plasma sampling. Observations on the therapeutic ranges and adverse effect of the drugs are reported.

Adolescent↗
PubMed1976

Carbamazepine pharmacokinetics in young, adult and pregnant rats. Relation to pharmacological effects.

Adult, male, female and pregnant rats were treated with single and repeated doses of carbamazepine (CBZ). The time course of the drug concentrations in plasma and tissues was followed. In all cases, data on plasma levels were subjected to pharmacokinetic analyses. Attempts were made to relate pharmacokinetic properties of carbamazepine to its effect on pentobarbital sleeping time and on protection against electroshock, after acute and repeated administration: --it was found that male rats eliminate carbamazepine faster than females: the total body clearance (TBC) was 16 ml/min/kg and 9.4 ml/min/kg, respectively. Two dose levels (25 and 50 mg/kg) had the same pharmacokinetic properties in young rats. Pregnant rats clear CBZ to a lesser extent than controls. --CBZ was found to accelerate its own elimination after repeated administration in both adult and young rats as revealed by the shortening of its half-life and an increase of 50% in clearance. Moreover, the protection against electroshock was significantly reduced after repeated administration, compared with a single-dose administration. Repeated administration of CBZ in rats shortens pentobarbital sleeping time and decreases the pentobarbital brain level significantly.

Aging↗