Rapid mapping of cloned DNA fragments on the Salmonella chromosome.
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Animals↗
Biomedical subjects
T Ali
Publications and source records attributed to T Ali.
Repair of chronic tympanic membrane perforations with long-term epidermal growth factor.
Chronic tympanic membrane (TM) perforation is a common problem worldwide. Recent reports have shown epidermal growth factor (EGF) to stimulate healing in approximately 80% of chronic TM perforations in chinchillas when applied in three doses over 1 week. The objective of this controlled study is to evaluate the efficacy of long-term EGF in the closure of TM perforations. Chronic chinchilla TM perforations were treated with EGF for up to 6 weeks. One hundred percent (17 of 17) of treatment group perforations completely healed. However, two new findings with this long dosing scheme were reperforation on long-term follow-up and three TMs with cholesteatomas. It is likely that reperforation was due to a progressive thinning seen with prolonged EGF application. Long-term EGF use is not recommended for the treatment of TM perforations because of possible wound healing impairment and possible cholesteatoma induction.
Animals↗
Construction, expression, and immunogenicity of multiple tandem copies of the Schistosoma mansoni peptide 115-131 of the P28 glutathione S-transferase expressed as C-terminal fusions to tetanus toxin fragment C in a live aro-attenuated vaccine strain of Salmonella.
Genetic fusions have been constructed between the highly immunogenic but atoxic fragment C of tetanus toxin and a guest peptide, aa115-131, from the protective 28-kDa glutathione S-transferase Ag of Schistosoma mansoni. Fusions have been assembled to express one, two, four, and eight tandem copies of the peptide. The recombinant vectors have been electroporated into the nonvirulent aroA strain of Salmonella typhimurium SL3261. The fusion proteins are soluble and stably expressed in Salmonella as evaluated by Western blotting with fragment C and glutathione S-transferase antisera. Mice have been immunized i.v. with a single dose of the live recombinant salmonellae. The strains are stable in mice and elicit Ab responses directed against fragment C, as determined by enzyme-linked immunosorbent assays. Ab responses were also detected against the guest peptide. The Ab responses improved dramatically toward the aa115-131 peptide with increasing copy number, with the octameric "repitope" fusion displaying the greatest potency. This approach may represent a general strategy for eliciting immune responses against peptides in live bacterial vaccines.
Amino Acid Sequence↗
Construction, expression, and immunogenicity of the Schistosoma mansoni P28 glutathione S-transferase as a genetic fusion to tetanus toxin fragment C in a live Aro attenuated vaccine strain of Salmonella.
A vector has been constructed to allow genetic fusions of guest antigens via a hinge domain to the C terminus of the highly immunogenic C fragment of tetanus toxin. A fusion has been constructed with the gene encoding the protective 28-kDa glutathione S-transferase (EC 2.5.1.18) from Schistosoma mansoni. The recombinant vector has been electroporated into the nonvirulent Salmonella typhimurium aroA live vaccine strain SL3261. The corresponding chimeric protein is stably expressed in a soluble form in Salmonella as evaluated by Western blotting with fragment C and glutathione S-transferase antisera. Mice immunized intravenously with a single dose of the live recombinant bacteria elicit antibodies to both fragment C and glutathione S-transferase as detected by enzyme-linked immunosorbent assays. Furthermore, all of the mice were solidly protected when challenged with lethal doses of either tetanus toxin or the virulent Salmonella typhimurium strain C5. Mice have also elicited antibodies to fragment C and glutathione S-transferase after oral immunization. It may be that a live trivalent vaccine against typhoid, tetanus, and schistosomiasis is feasible.
Animals↗
The measurement of injury severity.
Severity of injury can now be measured objectively and in a manner relevant to everyday practice. A variety of scales/scores are available which are based either on anatomical or physiological parameters or a combination of these. ASCOT methodology represents the most recent major contribution in this area, and follows AIS and TRISS as an established and reliable means of assessing trauma patients, particularly in relation to survival. These methods have clinical application in terms of triage, directing clinical management, assessing prognosis, assessing cost of management and for measuring outcome. The development of these scoring methods is outlined in this paper.
Humans↗
Role of hns in the virulence phenotype of pathogenic salmonellae.
A TnphoA-generated mutant C5060, attenuated for virulence, was derived from the mouse-virulent Salmonella typhimurium strain C5. This mutation, designated hns-112::TnphoA, harbours the transposon in the 3' end of hns, with the alkaline phosphatase open reading frame in the opposite orientation to that of hns. Bacterial strains harbouring hns-112::TnphoA were mucoid and had altered levels of DNA supercoiling, as monitored using pUC18 as a reporter plasmid. Transduction of hns-112::TnphoA into mouse virulent strains, including S. typhimurium SL1344 and Salmonella enteritidis Se795, resulted in attenuation. When an independent hns mutation, harbouring a kanamycin-resistance cassette inserted into the Kpnl site at base pair 237 of the hns gene, was introduced into S. typhimurium C5, the isolates were also attenuated. S. typhimurium C5 isolates harbouring the multicopy plasmid pGB651, which encodes the Escherichia coli hns gene, were partially attenuated in mice. Transductional analysis, using Tn10 insertions located close to the hns gene, showed that virulence could be restored in genetic crosses that eliminated the resident hns mutations. However, some hns+ transductants were still attenuated, suggesting that secondary attenuating lesions can accumulate in hns-deficient strains. These studies show that the hns locus plays a role in Salmonella virulence.
Animals↗
Fibrodysplasia ossificans progressiva. Report of a case in Trinidad and Tobago.
A case of fibrodysplasia ossificans progressiva is herein reported in a 27-year-old black woman. This is a very rare condition, the first to be reported from Trinidad and Tobago.
Adult↗
The role of a stress-response protein in Salmonella typhimurium virulence.
We recently described the use of selective transposon mutagenesis to generate a series of avirulent mutants of a pathogenic strain of Salmonella typhimurium. Cloning and sequencing of the insertion sites from two of these mutants reveals that both have identical locations within an open reading frame that is highly homologous to a gene, htrA, encoding a heat-shock protein in Escherichia coli. DNA sequence analysis of S. typhimurium htrA reveals the presence of a gene capable of encoding a protein with a calculated Mr of 49316 that has 88.7% protein:protein homology with its E. coli counterpart. In E. coli, lesions in this gene, also known as degP, reduce proteolytic degradation of aberrant periplasmic proteins. Characteristics of the S. typhimurium htrA mutants, 046 and 014, in vivo and in vitro suggested that they are avirulent because of impaired ability to survive and/or replicate in host tissues. In vitro, the S. typhimurium htrA mutants 046 and 014 are not temperature-sensitive but were found to be more susceptible to oxidative stress than the parent, suggesting that they may be less able to withstand oxidative killing within macrophages.
Alkaline Phosphatase↗
Sudden death in athletes in Trinidad and Tobago.
Sudden death related to exercise activity is a well-recognized clinical syndrome. Although the incidence is low, it is always an agonizing experience to all concerned when a young, relatively healthy individual dies suddenly. Over the last four years, we have had six proven cases of sudden death in athletes. The cause varied from congenital to acquired pathology of the heart, and there was one case of heat stroke. From this study, we were able to analyse some of the risk factors and, from a review of the literature, we are able to determine (1) the feasibility of a screening programme, and (2) the design of such a programme as would be suitable for our environment.
Adolescent↗
The role of a stress-response protein in bacterial virulence.
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Animals↗
Peripheral arterial embolism: prevalence, outcome, and the role of echocardiography in management.
The aims of this study were to review the prevalence and outcome of all surgically treated upper and lower limb emboli presenting to one vascular unit in the last 3 years and to compare transthoracic with transesophageal echocardiography for defining the source of the embolus. All patients who underwent surgical embolectomy for acute limb ischemia from January 2001 to June 2004 were reviewed. Transthoracic and transesophageal echocardiography were carried out on a subset of consecutive unselected patients. Forty-two patients, with a mean age of 80 years, underwent surgical embolectomy from January 2001 to June 2004 (M/F 1:1.8): 27 for lower limb ischemia and 15 for upper limb ischemia. Two thirds of these patients were found to be in atrial fibrillation at presentation (n = 28), of whom less than a third were receiving anticoagulants or antiplatelet agents (n = 8). The mean hospital stay was 15 days with 36 patients (86%) being fully anticoagulated before discharge from hospital. The 30-day mortality rate was 11% (n = 3/27) with 5 patients requiring fasciotomies (12%) and 3 patients requiring an amputation of the lower limb (11%). Postoperatively, 34 patients (81%) had transthoracic echocardiography (TTE), which demonstrated a source or potential source for thrombus in 19 (56%). Fifteen patients (36%) had transesophageal echocardiography (TEE), which changed the subsequent management in 3 patients. All patients in whom TEE altered clinical management would have required this investigation if standard clinical guidelines were followed. TEE did not identify any additional patients with cardiac embolic sources that were not detected by TTE. Arterial limb emboli are still prevalent, but limb salvage and mortality rates appear to be improving. Despite clear guidelines on anticoagulation for patients in atrial fibrillation, many are not receiving appropriate treatment. Transthoracic echocardiography is a good screening tool for detecting a potential cardiac source for peripheral embolism, with transesophageal echocardiography being reserved for specific indications.
Aged, 80 and over↗