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Biomedical subjects

F Franceschi

Publications and source records attributed to F Franceschi.

At least 73 records · Page 4Linked to original sources

Helicobacter pylori infection and vascular diseases.

Helicobacter pylori infection has recently been associated to some organic functional vascular disorders and, both observational and interventional studies have been carried out. A correlation between Helicobacter pylori infection and ischaemic heart disease was first described in 1994. Recent data, moreover, indicate a role of the bacterium in some functional vascular disorders such as primary headache and primary Raynaud phenomenon; indeed, some patients following eradication of Helicobacter pylori showed a significant improvement in the manifestations of these diseases. The host immune response against the bacterium may play an important role in the pathogenesis of vascular disorders, probably through a chronic stimulation of the release of vasoactive substances, such as cytokines, prostaglandins and others. However, various confounding factors such as co-infections, genetic and immunological host-factors, different strains of Helicobacter pylori or other may influence the data. Well designed case/control and randomized interventional studies are still needed to assess the real role of Helicobacter pylori in vascular disorders.

Antibodies, Bacterial↗

Vascular and immunological disorders associated with Helicobacter pylori infection.

Helicobacter pylori, the main aetiological factor for gastritis and peptic ulcer has been associated with some extradigestive diseases. In particular, vascular disorders, such as ischaemic heart disease, primary Raynaud phenomenon and headache appear to be related to the presence of the bacterium. Moreover, some autoimmune diseases, such as Henoch-Schonlein purpura, Sjögren syndrome and others have been shown to have a link with Helicobacter pylori infection Probably, in subjects with a particular predisposition, the release of substances with a vasoactive and proinflammatory activity, which is determined by Helicobacter pylori infection, may influence some extradigestive districts.

Antibodies, Bacterial↗

Characterization of DbpA, an Escherichia coli DEAD box protein with ATP independent RNA unwinding activity.

DbpA is a putative Escherichia coli ATP dependent RNA helicase belonging to the family of DEAD box proteins. It hydrolyzes ATP in the presence of 23S ribosomal RNA and 93 bases in the peptidyl transferase center of 23S rRNA are sufficient to trigger 100% of the ATPase activity of DbpA. In the present study we characterized the ATPase and RNA unwinding activities of DbpA in more detail. We report that-in contrast to eIF-4A, the prototype of the DEAD box protein family-the ATPase and the helicase activities of DbpA are not coupled. Moreover, the RNA unwinding activity of DbpA is not specific for 23S rRNA, since DbpA is also able to unwind 16S rRNA hybrids. Furthermore, we determined that the ATPase activity of DbpA is triggered to a significant extent not only by the 93 bases of the 23S rRNA previously reported but also by other regions of the 23S rRNA molecule. Since all these regions of 23S rRNA are either part of the 'functional core' of the 50S ribosomal subunit or involved in the 50S assembly, DbpA may play an important role in the ribosomal assembly process.

Adenosine Triphosphatases↗

Extraintestinal pathology associated with Helicobacter infection.

Helicobacter pylori appears to be the most important cause of gastritis and gastric and duodenal ulcer. Its eradication, in fact, promotes healing of these diseases and significantly reduces ulcer recurrence. In the last few years, moreover, besides a local tissue damage, an association between H. pylori infection and various extraintestinal pathologies has also been described. The presence of more toxic strains of H. pylori and the multiplicity of the substances produced, directly or indirectly, in response to the bacterium, besides a genetic predisposition of the individual, are all factors which may enhance the ability of Helicobacter to generate both local and systemic damage.

Bacterial Toxins↗

Central nervous system modifications in patients with lesion of the anterior cruciate ligament of the knee.

Patients with traumatic lesion of the anterior cruciate ligament often experience knee instability, which, recent studies suggest, is probably due to reduced knee proprioception. We studied knee proprioception and somatosensory evoked potentials (SEPs) after stimulation of the common peroneal nerve at the knee above the articular branches subserving the sensory innervation of the anterior cruciate ligament, in 19 patients with traumatic anterior cruciate ligament lesion. Ten patients showed decreased position sense of the knee, and of these, seven presented loss of cortical P27 potential while preserving lemniscal P20 and spinal N14 responses to common peroneal nerve stimulation on the side of the anterior cruciate ligament lesion. All our patients had normal SEPs to stimulation of the posterior tibial nerve at both the ankle and the knee. We suggest that in patients showing SEP abnormalities, the dysfunction of the central somatosensory conduction is located above the medial lemniscus and is limited to common peroneal nerve somatosensory pathways. Therefore, it is likely that in the seven patients showing SEP abnormalities, the loss of the knee mechanoreceptors was followed by remodelling of the CNS above the medial lemniscus. In five patients with P27 absence after common peroneal nerve stimulation, we also recorded SEPs after stimulation of the peroneal nerve at the ankle and obtained a normal cortical positive response; moreover, in our healthy subjects, cortical responses were significantly higher in amplitude after peroneal nerve than after common peroneal nerve stimulation. These findings strongly suggest that proprioceptive afferent inputs from the knee are more effective than distal afferent inputs in generating the greater part of the common peroneal nerve cortical SEPs. Since common peroneal nerve stimulation probably allows selective recording of the responses produced by the activation of the cortical representation of the knee, minor lesions with a reduction in the number of knee mechanoceptors could result in SEP changes after common peroneal nerve stimulation.

Adult↗

The suitability of a monofunctional reagent of an undecagold cluster for phasing data collected from the large ribosomal subunits from Bacillus stearothermophilus.

An electron density map of the large ribosomal subunit from Bacillus stearothermophilus was obtained at 26 A resolution by single isomorphous replacement (SIR) from a derivative formed by specific quantitative labeling with a dense undecagold cluster. For derivatization, a monofunctional reagent of this cluster was bound to a sulfhydryl group of a purified ribosomal protein, which was in turn reconstituted with core particles of a mutant lacking this protein. The native, mutated, and derivatized 50S ribosomal subunits crystallize under the same conditions in the same space group. Under favorable conditions, crystals of the derivatized subunit proved to be isomorphous with the native ones, whereas the crystals of the mutant may have somewhat different packing. After resolving the SIR phase ambiguity by solvent flattening, the electron density shows a packing that is consistent with the noncrystallographic symmetry found by Patterson searches as well as with the motif observed in electron micrographs of thin sections of the crystals. These studies established that phase information can be obtained from heavy metal clusters, even when the crystals under investigation are unstable and weakly diffracting. These results encouraged further effort at the construction of specifically derivatized crystals from other ribosomal particles that diffract to higher resolution.

Crystallography, X-Ray↗

Electron cryomicroscopy of Bacillus stearothermophilus 50 S ribosomal subunits crystallized on phospholipid monolayers.

50 S ribosomal subunits from Bacillus stearothermophilus have been crystallized as 2-dimensional periodic arrays on phospholipid monolayer films at the water-air interface. These crystals were preserved in vitreous ice and imaged with 100 keV electrons under low dose and low temperature conditions. The unit cell parameters of the crystals are a = 371.3(+/- 3.8) A, b = 152.3(+/- 1.6) A, gamma = 96.3(+/- 1.0) degrees. Some of the image arrays of these crystals have twofold rotational symmetry with a phase residual of less than 25 degrees. The mean figure of merit of the merged structure factors from these image arrays out to 20 A resolution is higher than 0.87. The 2-dimensional projection map shows a level of detail not seen in previous structural studies of the 50 S ribosome subunit. Some of these features may be related to the current 3-dimensional model of the subunit. This analysis illustrates the potential of using the electron crystallographic approach for determining the 3-dimensional structure of the 50 S ribosomal subunit crystallized on a monolayer surface. In addition, the structural information retrieved by electron crystallography might be useful for phasing X-ray data towards an atomic resolution model of the ribosome.

Crystallography↗

Crystallography of halophilic ribosome: the isolation of an internal ribonucleoprotein complex.

Crystals of 50S ribosomal subunits from Haloarcula marismortui diffracting to 2.9 A resolution were grown. Because of their large unit cells and the extremely weak diffracting power, almost all X-ray crystallographic analysis of these crystals must be performed with intense synchrotron radiation. At ambient temperature, all ribosomal crystals decay upon the first instance of X-irradiation. To overcome this severe sensitivity, procedures for data collection at cryo temperature were developed. Under these conditions the crystals can be irradiated for periods sufficient for the collection of more than one data set from an individual crystal (days or weeks) with no observable damage. They also can be stored for months, to resume interrupted measurements. To assist the interpretation of the anticipated electron density map, a specific internal nucleoprotein complex of protein HmaL1 and a stretch of H23S rRNA was isolated from the halophilic ribosome. The fragments of the 23S rRNA protected by the protein from nuclease digestion were sequenced. Alignment of the sequences of some archaebacterial L1-specific RNA fragments to the corresponding parts of eubacterial and eukaryotic rDNAs, localized the sequence identities to two distinct regions. Chimeric complexes were reconstituted with the corresponding E. coli ribosomal components, indicating a rather high homology, despite the evolution distance. A feasible secondary structure of the rRNA stretch participating in this complex was found to be compatible with the one proposed for the corresponding part in the E. coli ribosomal RNA.

Base Sequence↗

The reasons for amputations in children (0-18 years) in a developing country.

This study describes 49 young amputees who either have attended or have been operated at the Orthopaedic Department of Dodoma Regional Hospital from 1983 to 1991. Emphasis has been put on the aetiological factors of 56 amputations under review, underlying those that are typical of the Least Developed Countries in Africa and highlighting how they interrelate with the beliefs and traditions of the African society. Apart from 14 amputations performed for trauma of different type, important roles were played by home environment, tumours, wild animal bites and the health system itself. Nine amputations have been carried out for burns, while complications after medical care, particularly operative, have called for 12 amputations. Bone tumours have been responsible for eight and hyena assaults and snake bites have resulted in seven amputations. Special interest has been raised by four amputations performed for the so-called 'idiopathic tropical lower limbs gangrene' whose aetiology is still unknown.

Adolescent↗

Isolation and characterization of a new ribosomal protein from the thermophilic eubacteria, Thermus thermophilus, T. aquaticus and T. flavus.

A ribosomal protein, showing no homology with other known prokaryotic ribosomal proteins, was isolated and characterized from the thermophilic eubacteria, Thermus thermophilus, T. aquaticus and T. flavus. This small (26 amino acids) and strongly basic (1 acidic and 13 basic residues) protein displayed the same primary structure from all three sources. Interestingly, it shows about 65% homology with a ribosomal protein from spinach chloroplasts (J. Schmidt, personal communication).

Amino Acid Sequence↗

Apparent association constants of tRNAs for the ribosomal A, P, and E sites.

Association constants for tRNA binding to poly(U) programmed ribosomes were assessed under standardized conditions with a single preparation of ribosomes, tRNAs, and elongation factors, respectively, at 15 and 10 mM Mg2+. Association constants were determined by Scatchard plot analysis (the constants are given in units of [10(7)/M] measured at 15 mM Mg2+): the ternary complex Phe-tRNA.elongation factor EF-Tu.GTP (12 +/- 3), Phe-tRNA (1 +/- 0.4), AcPhe-tRNA (0.7 +/- 0.3), and deacylated tRNA(Phe) (0.4 +/- 0.15) bind with decreasing affinity to the A site of poly(U)-programmed ribosomes. tRNA(Phe) (7.2 +/- 0.8) binds to the P site with higher affinity than AcPhe-tRNA (3.7 +/- 1.3). The affinity of the E site for deacylated tRNA(Phe) (1 +/- 0.2) is about the same as that of the A site for AcPhe-tRNA (0.7 +/- 0.3). At lower Mg2+ concentrations the affinity of the E site ligand becomes stronger relative to the affinities of the A site ligands. Phe-tRNA and ternary complexes can occupy the A site at 0 degrees C in the presence of poly(U) even if the P site is free, whereas, as already known, deacylated tRNA or AcPhe-tRNA bind first to the P site of programmed ribosomes. Hill plot analyses of the binding data confirm an allosteric linkage between A and E sites in the sense of a negative cooperativity.

Acylation↗

Human bites and finger infections: a survey at Dodoma Regional Hospital, Tanzania.

We describe 26 patients with finger infections following human bites, who were admitted to Dodoma Regional Hospital in Tanzania between 1983 and 1991. Most patients came to hospital too late for the finger to be saved, and amputation was necessary in nearly all cases. The extreme seriousness of the bite seems to have been overlooked by both the patients and the health workers of the peripheral units of our region.

Adult↗

Revision of amputation stumps in Dodoma--Tanzania.

The records of Dodoma Orthopaedic Department, Tanzania were reviewed for the period July 1986 to December 1990 in order to identify the reasons for revision surgery. A total of 26 patients required revision surgery. Two main groups were identified. In the first group 4 patients had a higher level of amputation because of gangrene. In the second group 22 patients had revision surgery because of other stump defects caused by technical mistakes when carrying out the original amputation, or other complications.

Adolescent↗