Angiosarcoma: a difficult diagnosis.
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Adult↗
Biomedical subjects
B Kenny
Publications and source records attributed to B Kenny.
Acute gastric dilatation in a child with marked kyphoscoliosis and cerebral palsy--a case report.
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Adolescent↗
Solitary fibrous tumour of the falciform ligament containing multiple foci of malignant transformation.
Solitary fibrous tumour is an uncommon soft tissue tumour initially described in the pleural cavity. In the past decade, it has been described in various extrapleural sites, including the abdomen. Traditionally regarded as benign, cases of histologically or clinically malignant solitary fibrous tumours are rare. This report describes such a case, although the patient is still disease free five years after excisional surgery, without adjuvant treatment. The acute clinical presentation may be related to malignant transformation occurring in a long standing solitary fibrous tumour.
Acute Disease↗
Endovascular exclusion of iliac artery to iliac vein fistula after lumbar disk surgery.
Iliac arteriovenous (AV) fistula is rare after lumbar disk surgery. Traditionally, open repair through the arterial lumen was performed. We report endovascular exclusion of an iliac AV fistula in a 41-year-old woman 8 years after lumbar diskectomy. An angiogram showed an AV fistula connecting the right common iliac artery and vein. This was repaired with placement of two covered wall stents in the right common artery and external iliac artery, and embolization of the right internal iliac artery. Contrast medium-enhanced computed tomography scan at 5 months confirmed elimination of the AV fistula and right iliac artery patency. This technique should be considered in management of iliac AV fistulas.
Adult↗
Phosphoserine modification of the enteropathogenic Escherichia coli Tir molecule is required to trigger conformational changes in Tir and efficient pedestal elongation.
Enteropathogenic Escherichia coli (EPEC) virulence is correlated with intimate adherence to gut epithelial cells, loss of absorptive microvilli and reorganization of host cytoskeletal proteins into pedestal-like structures beneath the adherent bacteria. These processes depend on Tir (i) being inserted into the plasma membrane; (ii) being tyrosine phosphorylated; and (iii) interacting with the bacterial outer membrane protein, intimin. However, phosphorylation on other undefined residues leads to approximately 5 kDa and approximately 2 kDa increases in Tir apparent molecular mass within host cells. In this study, we show that equivalent shifts can be induced in vitro by phosphorylation of Tir on two serine (S434 and S463) residues by protein kinase A (PKA). Our data suggest that the sequential addition of two phosphate groups triggers conformational changes in Tir structure that may supply the energy to insert Tir into the plasma membrane. PKA was also shown to modify Tir within host cells on S434 to induce the approximately 5 kDa shift. Whereas modification of S434 was not essential to generate an actin-nucleating molecule, it was required for Tir to induce pedestal elongation efficiently. This study not only increases our understanding of the mechanism by which phosphorylation induces shifts in Tir apparent molecular mass and suggests a mechanism by which Tir may be inserted into the plasma membrane, but also reveals a role for non-tyrosine phosphorylation in Tir function and identifies the first kinase that can modify Tir in vitro or in vivo.
Amino Acid Substitution↗
Role of sipA in the early stages of Salmonella typhimurium entry into epithelial cells.
Salmonella virulence depends on an ability to invade host cells, which is in turn dependent on a type III protein secretion system encoded in Salmonella pathogenicity island 1 (SPI1). Several protein targets of the SPI1-encoded secretion system are translocated into host cells, where they subvert cellular processes that contribute to bacterial invasion, actin rearrangement, membrane ruffling and other aspects of virulence. We examined the role of sipA (encoding the translocated protein SipA) and found that a sipA mutant was significantly less invasive in Madin-Darby canine kidney (MDCK) cells than in its parental strain at the earliest stages of infection (5 min). The invasion defect associated with sipA was no longer apparent after 15 min of infection. Confocal microscopy of F-actin in tetramethyl rhodamine isothiocyanate (TRITC)-phalloidin-stained MDCK cells revealed no difference in either the frequency or the morphology of membrane ruffles induced by wild-type and sipA mutant strains of S. typhimurium. Time-lapse phase-contrast microscopy of membrane ruffle propagation in live cells confirmed that the sipA mutant induced membrane ruffles as efficiently as the wild-type bacteria. These studies also revealed that, after ruffle propagation, individual sipA mutant S. typhimurium either invaded more slowly than wild-type bacteria or failed to invade at all. Furthermore, although wild-type S. typhimurium typically maintained a position central to the developing membrane ruffle, sipA mutant bacteria frequently moved initially to the periphery of the spreading ruffle and were sometimes observed to detach from it. A wild-type pattern of invasion was restored to the sipA mutant after the introduction of sipA on a plasmid. Together, these data indicate that loss of sipA significantly decreases the efficiency of S. typhimurium invasion at the early stages of infection without affecting its ability to induce membrane ruffles. It thus appears that the secreted effector protein SipA promotes invasion by a previously unrecognized mechanism separate from the induction of membrane ruffling per se.
Actins↗
The enterohaemorrhagic Escherichia coli (serotype O157:H7) Tir molecule is not functionally interchangeable for its enteropathogenic E. coli (serotype O127:H6) homologue.
A major virulence determinant of enteropathogenic Escherichia coli (EPEC) is the Tir molecule that is translocated into the plasma membrane where it orchestrates cytoskeletal rearrangements. Tir undergoes several phosphorylation events within host cells, with modification on a tyrosine essential for its actin-nucleating function. The EHEC (serotype O157:H7) Tir homologue is not tyrosine phosphorylated implying that it uses an alternative mechanism to nucleate actin. This is supported in this study by the demonstration that EHEC Tir is unable to functionally substitute for its EPEC homologue. Like EPEC, the EHEC Tir molecule is phosphorylated within host cells, with the actin-nucleating dysfunction correlated to an altered modification profile. In contrast to EHEC Tir, the EPEC Tir molecule mediated actin nucleation whether delivered into host cells by either strain. Thus, it would appear that EHEC encodes specific factor(s) that facilitate the correct modification of its Tir molecule within host cells. Domain-swapping experiments revealed that the N-terminal, alpha-actinin binding, Tir domains were functionally interchangeable, with both the actin-nucleating dysfunction and altered modification profiles linked to the EHEC C-terminal Tir domain. This tyrosine-independent modification process presumably confers an advantage to EHEC O157:H7 and may contribute to the prevalence of this strain in EHEC disease. The presented data are also consistent with EPEC and EHEC sharing non-phosphotyrosine phosphorylation event(s), with an important role for such modifications in Tir function. An EHEC-induced phosphotyrosine dephosphorylation activity is also identified.
Actins↗
Enteropathogenic Escherichia coli (EPEC) Tir receptor molecule does not undergo full modification when introduced into host cells by EPEC-independent mechanisms.
Enteropathogenic Escherichia coli (EPEC), like many other gram-negative pathogens, encodes a type III secretion apparatus dedicated to the release of virulence-associated proteins. One such protein, Tir, is translocated into host cells, where it is modified by the addition of phosphate groups, resulting in a number of species with distinct molecular mass. One phosphorylation event, on tyrosine residue 474 of Tir, does not contribute to shifts in molecular mass but is essential for its actin-nucleating function. The role of the nonphosphotyrosine related modifications is unknown. In this paper, we demonstrate, using three different approaches, that Tir does not encode sufficient information to facilitate its complete modification when introduced into host cells in EPEC-independent mechanisms. Each system revealed that Tir is a substrate for a host kinase whose action results in its partial modification to a form similar to one evident in EPEC-infected host cells. Further Tir modification could not be induced by infecting cells with EPEC, suggesting that Tir must be coexpressed with other EPEC factors to enable its full modification within host cells. One approach used Yersinia spp. to deliver Tir into host cells, and this system revealed that Tir secretion and translocation can occur in the absence of the Tir chaperone molecule, CesT (formerly known as OrfU). CesT was found to be an efficiency factor which was not required, unlike in EPEC, for Tir stability, indicating that it may function to guide Tir to the translocation apparatus or maintain it in a secretion-competent form.
Bacterial Proteins↗
Targeting of an enteropathogenic Escherichia coli (EPEC) effector protein to host mitochondria.
Many Gram-negative pathogens use a type III secretion apparatus to deliver effector molecules into host cells to subvert cellular processes in favour of the pathogen. Enteropathogenic Escherichia coli (EPEC) uses such a system to deliver the Tir effector molecule into host cells. In this paper, we show that the gene upstream of tir, orf19, encodes an additional type III secreted effector protein. Orf19 is delivered into host cells by a mechanism independent of endocytosis, but dependent on EspB. Orf19 is targeted to host mitochondria, where it appears to interfere with the ability to maintain membrane potential. Although the precise role of Orf19 remains to be elucidated, its interaction with mitochondria suggests a possible role in the subversion of key functions of these organelles, such as energy production or control of cell death. This is the first example of a type III secreted protein targeted to mitochondria; it is probable that homologues (present in EPEC and Shigella species) and other bacterial effectors will also target this organelle.
Bacterial Outer Membrane Proteins↗
Intraarterial catheter-directed thrombolysis: urokinase versus tissue plasminogen activator.
The purpose of this study was to evaluate the differences between tissue plasminogen activator (TPA) and urokinase (UK) in the management of ischemic limbs. A total of 58 limbs (24 in the TPA group and 34 in the UK group) in 53 patients were studied prospectively. The two groups were based on the surgeon's preference for lytic agent. The dose regimen for UK was 150,000 IU/hr over 1/2 to 2 hr followed by a continuous infusion of 50,000 IU/hr. TPA was given as a 5-mg bolus followed by 1 mg/hr. Both groups received heparin at a rate of 400 IU/hr through the side arm of the arterial sheath. There was no significant difference in efficacy between UK and TPA, but TPA acted faster and had a higher incidence of bleeding complications.
Aged↗
Phosphorylation of tyrosine 474 of the enteropathogenic Escherichia coli (EPEC) Tir receptor molecule is essential for actin nucleating activity and is preceded by additional host modifications.
The enteropathogenic Escherichia coli (EPEC) Tir protein becomes tyrosine phosphorylated in host cells and displays an increase in apparent molecular mass. The interaction of Tir with the EPEC outer membrane protein, intimin, triggers actin nucleation beneath the adherent bacteria. The enterohaemorrhagic E. coli O157:H7 (EHEC) Tir molecule is not tyrosine phosphorylated. In this paper, Tir tyrosine phosphorylation is shown to be essential for actin nucleation activity, but not for the increase in apparent molecular mass observed in target cells. Tyrosine phosphorylation had no role in Tir molecular mass shift, indicating additional host modifications. Analysis of Tir intermediates indicates that tyrosine-independent modification functions to direct Tir's correct insertion from the cytoplasm into the host membrane. Deletion analysis identified Tir domains participating in translocation, association with the host membrane, modification and antibody recognition. Intimin was found to bind a 55-amino-acid region (TIBA) within Tir that topological and sequence analysis suggests is located in an extracellular loop. Homologous TIBA sequences exist in integrins, which also bind intimin. Collectively, this study provides definitive evidence for the importance of tyrosine phosphorylation for EPEC Tir function and reveals differences in the pathogenicity of EPEC and EHEC. The data also suggest a mechanism for Tir insertion into the host membrane, as well as providing clues to the mode of intimin-integrin interaction.
Actins↗
Consumer attitudes and behaviours--key risk factors in an outbreak of Salmonella typhimurium phage type 12 infection sourced to chicken nuggets.
OBJECTIVES: To identify the source and intervention methods for an outbreak of Salmonella Typhimurium phage type 12 in South Australia. METHOD: Ten cases of S. Typhimurium phage type (PT) 12 infection were notified in South Australia in a four-week period from 7 May 1998. Nine cases and 27 controls were included in a case control study to test the hypothesis that illness was associated with the consumption of chicken nuggets. RESULTS: A significant association between illness and the consumption of one brand of chicken nuggets was determined, odds ratio undefined (95% CI undefined; p = undefined). Nine of nine cases and one of 27 controls reported eating these chicken nuggets. S. Typhimurium PT 12 was isolated from an opened sample of this particular brand of nuggets which had been retrieved from the home of one case. CONCLUSIONS AND IMPLICATIONS: The implicated nuggets were essentially a raw product which had been 'flash fried' in contrast with other brands which were fully cooked. The investigation highlighted issues of inadequate labelling and consumer responses to labelling information which affect food safety. A media release to highlight to the consumer the need to cook frozen food properly and a voluntary recall of the 'flash fried' product was instigated as a result of these conclusions. Further action is needed to eliminate the potential hazard that consumers will perceive and handle 'flash fried' nuggets as if they are a cooked chicken product.
Adolescent↗
Type III secretion-dependent hemolytic activity of enteropathogenic Escherichia coli.
Enteropathogenic Escherichia coli (EPEC) was found to exhibit a type III secretion-dependent, contact-mediated, hemolytic activity requiring the EspA, EspB, and EspD secreted proteins. EspB and EspD display homology to pore-forming molecules. Our data suggest a mechanism to explain the requirement for all three Esp proteins in the transfer of EPEC proteins, such as Tir, into target cells.
Amino Acid Sequence↗
Enteropathogenic Escherichia coli inhibits phagocytosis.
Enteropathogenic Escherichia coli (EPEC) interacts with intestinal epithelial cells, activating host signaling pathways leading to cytoskeletal rearrangements and ultimately diarrhea. In this study, we demonstrate that EPEC interacts with the macrophage-like cell line J774A.1 to inhibit phagocytosis by these cells. Antiphagocytic activity was also observed in cultured RAW macrophage-like cells upon EPEC infection. The EPEC antiphagocytic phenotype was dependent on the type III secretion pathway of EPEC and its secreted proteins, including EspA, EspB, and EspD. Intimin and Tir mutants displayed intermediate antiphagocytic activity, suggesting that intimate attachment mediated by intimin-Tir binding may also play a role in antiphagocytosis. Tyrosine dephosphorylation of several host proteins was observed following infection with secretion-competent EPEC but not with secretion-deficient mutants. Dephosphorylation was detectable 120 min after infection with EPEC, directly correlating with the onset of the antiphagocytic phenotype. Inhibition of protein tyrosine phosphatases by pervanadate treatment increased the number of intracellular wild-type EPEC organisms to levels seen with secretion-deficient mutants, suggesting that dephosphorylation events are linked to the antiphagocytic phenotype. No tyrosine phosphatase activity was detected with the EPEC-secreted proteins, suggesting that EPEC induces antiphagocytosis via a different mechanism than Yersinia species. Taken together, the present findings demonstrate a novel function for EPEC-secreted proteins in triggering macrophage protein tyrosine dephosphorylation and inhibition of phagocytosis.
Animals↗
Enteropathogenic E. coli (EPEC) transfers its receptor for intimate adherence into mammalian cells.
Enteropathogenic E. coli (EPEC) belongs to a group of bacterial pathogens that induce epithelial cell actin rearrangements resulting in pedestal formation beneath adherent bacteria. This requires the secretion of specific virulence proteins needed for signal transduction and intimate adherence. EPEC interaction induces tyrosine phosphorylation of a protein in the host membrane, Hp90, which is the receptor for the EPEC outer membrane protein, intimin. Hp90-intimin interaction is essential for intimate attachment and pedestal formation. Here, we demonstrate that Hp90 is actually a bacterial protein (Tir). Thus, this bacterial pathogen inserts its own receptor into mammalian cell surfaces, to which it then adheres to trigger additional host signaling events and actin nucleation. It is also tyrosine-phosphorylated upon transfer into the host cell.
Adhesins, Bacterial↗
Pharmacological options in the treatment of benign prostatic hyperplasia.
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5-alpha Reductase Inhibitors↗
Intimin-dependent binding of enteropathogenic Escherichia coli to host cells triggers novel signaling events, including tyrosine phosphorylation of phospholipase C-gamma1.
Enteropathogenic Escherichia coli (EPEC) interactions with HeLa epithelial cells induced the tyrosine phosphorylation of a host protein of approximately 150 kDa, Hp150. Phosphorylation of this protein band was dependent on the interaction of the EPEC protein intimin with epithelial cell surfaces and was correlated with pedestal formation. Hp150 phosphorylation was specifically inhibited by the addition of cytochalasin D, an inhibitor of actin polymerization, although this appeared to be an indirect effect preventing interaction of intimin with its receptor, tyrosine-phosphorylated Hp90, and thus triggering Hp150 phosphorylation. This suggests the involvement of an actin-based movement of membrane-bound tyrosine-phosphorylated Hp90 to allow its interaction with intimin. Analysis of the tyrosine-phosphorylated Hp150 protein demonstrated that it is heterogeneous in composition, with phospholipase C-gamma1 (PLC-gamma1) being a minor component. Activation of PLC-gamma1 by tyrosine phosphorylation leads to inositol triphosphate and Ca2+ fluxes, events detected following EPEC infection. EPEC also induced tyrosine dephosphorylation of host proteins, including a 240-kDa host protein (Hp240), following EPEC infection. Protein dephosphorylation appears to be a signaling event which occurs independently of intimin. Inhibition of host tyrosine dephosphorylation events by the addition of the tyrosine phosphatase inhibitor sodium vanadate did not prevent actin accumulation beneath the adherent bacteria. We conclude that EPEC induces two sets of signaling events following infection. One set is dependent on EPEC proteins secreted by the type III secretion pathway (EspA and EspB) which induces Hp90 tyrosine phosphorylation and dephosphorylation of host phosphotyrosine proteins. The second set, which is also dependent on the first signaling events, requires intimin interaction with its receptor, tyrosine-phosphorylated Hp90, to trigger Hp150 and PLC-gamma1 tyrosine phosphorylation as well as pedestal formation. Inhibition of pedestal formation by tyrosine kinase inhibitors indicates an important role for tyrosine phosphorylation events during EPEC subversion of host processes.
Adhesins, Bacterial↗
Enteropathogenic Escherichia coli protein secretion is induced in response to conditions similar to those in the gastrointestinal tract.
The pathogenicity of enteropathogenic Escherichia coli (EPEC) is associated with the expression and secretion of specific bacterial factors. EspB is one such secreted protein which is required to trigger host signaling pathways resulting in effacement of microvilli and cytoskeletal rearrangements. These events presumably contribute to the ensuing diarrhea associated with EPEC infections. EPEC encounters several environmental changes and stimuli during its passage from the external environment into the host gastrointestinal tract. In this paper we show that the secretion of EspB is subject to environmental regulation, and maximal secretion occurs under conditions reminiscent of those in the gastrointestinal tract. Thus, secretion is maximal at 37 degrees C, pH 7, and physiological osmolarity. In addition, maximal secretion requires the presence of sodium bicarbonate and calcium and is stimulated by millimolar concentrations of Fe(NO3)3. The secretion of the four other EPEC-secreted proteins appears to be modulated in a manner similar to that of EspB. Our results also show that secretion is not dependent on CO2, as originally reported by Haigh et al. (FEMS Microbiol. Lett. 129: 63-67, 1995), but that CO2 more likely acts as a component of the medium buffering system, since CO2 dependence was abolished by the use of alternative buffers.
Ammonium Chloride↗