Biomedical subjects
Publications and source records attributed to A Marra.
The sigB gene of Staphylococcus aureus, coding for the alternate sigma factor B, has been deleted by allelic replacement mutagenesis. The mutant grew as well as the parent in vitro, although it was deficient in clumping factor, coagulase, and pigment. In two murine and one rat infection model the mutant showed no reduction in virulence.
The ability to selectively disrupt gene function remains a critical element in elucidating information regarding gene essentiality for bacterial growth and/or pathogenesis. In this study, we adapted a tet regulatory expression system for use in Staphylococcus aureus, with the goal of downregulating gene expression via induction of antisense RNA. We demonstrate that this system exhibits a 50- to 100-fold dose-dependent level of induction in bacterial cells grown in culture (i.e., in vitro) and also functions in mice (i.e., in vivo) following oral administration of inducer. To determine whether induced antisense RNA could interfere with chromosomally derived gene expression, we cloned a fragment of the S. aureus alpha-toxin gene (hla) in antisense orientation downstream of the tet promoter system and introduced the construct into S. aureus. Induced antisense hla RNA downregulated chromosomally derived hla gene expression in vitro approximately 14-fold. Similarly, induction of hla antisense RNA in vivo dramatically reduced alpha-toxin expression in two different murine models of S. aureus infection. Most importantly, this reduction completely eliminated the lethality of the infection. These results indicate that the tet regulatory system functions efficiently in S. aureus and induced antisense RNA can effectively downregulate chromosomal gene expression both in vitro and in vivo.
This paper first goal is to establish what "critical" aneurysm means. We decided to consider as "critical" aneurysms those whose correct clipping-treatment would be particularly difficult; this particular difficulty could concern the malformation intrinsic characteristics as well as extrinsic factors (the patient's clinical conditions as well as insufficient organizational or technical facilities). We thus reviewed 277 aneurysms operated in the Neurosurgical Department of Varese from 1988 to 1994. We excluded 18 vertebro-basilar system aneurysms; the clinical and surgical charts of the 259 remaining aneurysms were reviewed and informations regarding their last clinical conditions were gathered. In this way it was possible for us to distinguish different categories of critical aneurysms: critical for their anatomical position, morphology, size and for their number; unpredictably critic aneurysms and aneurysms associated with the patient's critical conditions were also considered. After describing our technical solutions and those suggested by the current literature we concluded that what is required to treat these critical aneurysms is not an extraordinary surgical skill, but a good organizational and technical facility at the surgical-team's disposal.
Yersinia pseudotuberculosis initiates systemic disease after translocation across the intestinal epithelium. Three Y. pseudotuberculosis factors, previously identified by their ability to promote association with cultured cells, were evaluated for their relative roles in translocation. To this end, mutants defective for invasin, YadA, or pH 6 antigen were tested for movement from the intestinal lumen into the subepithelium. Within 45 min after introduction of bacteria into the lumen, wild-type bacteria were found in the Peyer's patch. Mutants expressing defective invasin derivatives were unable to promote efficient translocation into the Peyer's patch and instead colonized on the luminal surface of the intestinal epithelium. In particular, a translocation defect was observed in a Y. pseudotuberculosis strain that expressed an uptake-defective invasin protein retaining considerable receptor binding activity. To attempt to reduce binding to luminal mucus, Y. pseudotuberculosis yadA and inv yadA strains were analyzed. Both strains had reduced mucus binding, with the inv yadA mutant revealing an alternate uptake pathway that was invasin independent. A mutant defective in the production of the pH 6 antigen adhesin also showed reduced binding to luminal mucus, with specific localization of bacteria in M cells. These results indicate that Y. pseudotuberculosis adhesive factors control the site of bacterial interaction within the intestinal environment and that loss of one factor causes drastic changes in the preferred site of localization of the bacterium in this locale.
Two cases of association between intracranial meningioma and cerebral artery aneurysm are reported. A 50-year-old woman had a petroclival meningioma with a carotid-ophthalmic artery aneurysm; the surgery was performed first for the aneurysm then for the meningioma with good results. The second patient, a 67-year-old woman, had an olfactory meningioma with a carotid-posterior communicating artery aneurysm treated successfully in the same procedure. The pertinent literature is reviewed and the localization of meningiomas and aneurysms, the surgical treatment and the results at distance are discussed. It seems advisable, when possible, the contemporaneous treatment of the two lesions.
Explore the source record for details and available documents.
The recent identification of E-cadherin as the cell-surface receptor for the Listeria monocytogenes adhesin, internalin, indicates that pathogenic bacteria exploit a variety of host surface molecules for entry and that they may share some common strategies for uptake into host cells.
OBJECTIVES: To investigate the impact of age as a prognostic factor in older patients with breast cancer and to discuss the role of surgery in this category of patients. DESIGN: A retrospective study. SETTING: A tertiary care university teaching hospital. PARTICIPANTS: One hundred ninety patients aged 70 years or older (mean age: 75 years) were treated for breast cancer from 1967 through 1991. These patients were compared with 190 younger patients (mean age: 52 years) and matched on the basis of T and N categories (TNM staging system) and surgical procedures. MEASUREMENTS: Disease-free survival, breast cancer-specific survival. RESULTS: The 10-year actuarial breast cancer-specific survival was 66% for older patients and 56% for younger patients (P = .224). The 10-year actuarial disease-free survival was 54% for older patients and 45% for younger patients (P = .136). Univariate and multivariate survival analysis revealed that tumor size and nodal stage were significant prognostic factors for both older and younger patients. CONCLUSION: Treatment with curative intent, similar to that adopted in younger patients, is appropriate for women over the age of 70 with breast cancer.
The Yersinia pseudotuberculosis invasin protein mediates bacterial entry into mammalian cells by binding multiple beta 1-chain integrins. Invasin binding to purified alpha 5 beta 1 integrin is inhibited by Arg-Gly-Asp (RGD)-containing peptides, although invasin contains no RGD sequence. Fifteen mutations that diminished binding and bacterial entry were isolated after mutagenesis of the entire inv gene. All of the mutations altered residues within the C-terminal 192 amino acids of invasin, previously delineated as the integrin binding domain, and 10 of the mutations fell within an 11 residue region. This small region was subjected to site-directed mutagenesis and almost half of the 35 mutations generated decreased invasin-mediated entry. D911 within this region was the most critical residue, as even a conservative glutamate substitution abolished bacterial penetration. Purified invasin derivatives altered at this residue were defective in promoting cell attachment and this defect was reflected in a 10-fold or greater increase in IC50 for integrin binding. D911 may have a function similar to that of the aspartate residue in RGD-containing sequences.
The authors describe the case of a 58-year-old man with an history of seizures because of right parietal parasagittal meningioma. Twenty-two months after complete removal of this neoplasm, the patient showed progressive mental deterioration and at CT-scans revealed a right temporal anaplastic astrocytoma which was operated. In literature the association between intracranial meningioma and astrocytoma is reported in 41 cases. After a brief review of the previous cases, the authors debate the clinical presentation, the diagnostic problems, the aetiopathogenetic hypotheses and the best surgical treatment of this association.
Derivatives of the self-transmissible F plasmid of Escherichia coli can be introduced into Legionella pneumophila by conjugation and maintained within only upon selection. In L. pneumophila. F-based replicons seem to exist as extrachromosomal elements since they were readily lost when F-containing L. pneumophila was grown on nonselective medium. The F-based plasmids were not self-transmissible in L. pneumophila. The mating defect may be due to an inability to form the F pilus since F-containing strains of L. pneumophila could neither be infected with the pilus-specific phage M13 nor transduced with f1-packaged ColE1 replicons. Currently, the most commonly used transfer system for introducing genetic information into L. pneumophila employs E. coli donors with a chromosomally integrated copy of RP4::Mu to mobilize plasmids bearing the RK2 origin of transfer (oriT). Use of this system to deliver TnphoA for mutagenesis of the L. pneumophila chromosome led to transconjugants that all contained cryptic DNA alterations that involved the plasmid RP4 and phage Mu. No TnphoA transposition was observed in L. pneumophila. The fact that F-mediated conjugation can be used to efficiently transfer plasmids containing the oriT of F to L. pneumophila provides an important alternative to the RP4-based plasmid transfer system and may avoid DNA anomalies in transconjugants that impede genetic analysis. Furthermore, our results demonstrate the promiscuous nature of the F conjugal transfer and replication systems.
We assessed the feasibility of percutaneous treatment of a cervical herniated disc. In the lumbar region, the surgical instrument for percutaneous diskectomy passes only through the paravertebral muscles, while in the cervical region there is considerable risk of nervous, parenchymal and vascular lesions. Moreover, open surgery for cervical herniated nucleus pulposus is a well-established, low-risk procedure, with little risk of epidural fibrosis, the main complication of lumbar open surgery; a percutaneous procedure should therefore have a low morbidity rate. A safe percutaneous approach to cervical discs could be useful for biopsy and for treatment of high-risk patients for general anaesthesia. We treated 15 patients with cervical herniated nucleus pulposus; all gave informed consent and refused or were not eligible for open surgery. We used the Nucleotome described for treatment of lumbar herniated discs; except for the first three cases, we used colour Doppler sonography to detect hazardous structures in the path of the probe. We had one complication, a cervical haematoma due to damage to the inferior thyroid artery, prior to the use of ultrasound.
The detailed structure of the symbiotically important exopolysaccharide succinoglycan from Rhizobium meliloti Rm1021 was determined by mass spectrometry with electrospray ionization and collision-induced dissociation of the octameric oligosaccharide repeating unit. Previously undetermined locations of the succinyl and acetyl modifications were determined, in respect to both residue locations within the octamer and the carbon positions within the pyranose ring. Glycosidic linkages determined previously by methylation analysis were also verified.
The authors describe the rare case of a 50-year-old man with lumbar neurinoma associated with hydrocephalus. The complete neuroradiological study is presented. The various explanations about the pathogenesis of the hydrocephalus and the management of this condition are debated.
The authors present two cases of non-traumatic subdural haematomas associated with a meningioma. Relevant literature is reviewed and the pathogenesis of this rare condition is discussed.
The more and more availability of new alloplastic materials in oral and maxillo-facial reconstructions causes the necessity of judging if the biomaterials satisfy the surgical needs. The authors re-examine the main chemical, physical and biological characteristics of following materials: hydroxylapatite, polytetrafluoroethylene, polyglactin 910, polyfluorocarbons, polypropylene and report their experiences.
The very rare case of association of anterior communicating artery aneurysm and a right frontal cavernoma not visualized by CT-scan and angiography in a 37-year-old man is described. The rarity and the possible pathogenesis of this association are discussed.
The case of a 63-year-old patient with spontaneous cerebrospinal fluid rhinorrhea from a intraethmoidal encephalomeningocele is presented. The patient was asymptomatic until the old age. The preoperative coronal CT-scan and the preoperative and postoperative MRI are shown. The rarity of this onset in an elderly man and the surgical indications of this disease are debated.