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Biomedical subjects

S Swift

Publications and source records attributed to S Swift.

At least 19 recordsLinked to original sources
PubMed2006

EGFR amplification and lack of activating mutations in metaplastic breast carcinomas.

Metaplastic breast carcinomas are reported to harbour epidermal growth factor receptor (EGFR) overexpression in up to 80% of the cases, but EGFR gene amplification is the underlying genetic mechanism in around one-third of these. In this study, EGFR gene amplification as defined by chromogenic in situ hybridization and protein overexpression was examined in a cohort of 47 metaplastic breast carcinomas. Furthermore, the presence of activating EGFR mutations in exons 18, 19, 20, and 21 was investigated. Thirty-two cases showed EGFR overexpression and of these, 11 (34%) harboured EGFR gene amplification. In addition, EGFR amplification showed a statistically significant association with EGFR overexpression (p < 0.0094) and was restricted to carcinomas with homologous metaplasia. Ten cases, five with and five without EGFR amplification, were subjected to microarray-based CGH, which demonstrated that EGFR copy number gain may occur by amplification of a discrete genomic region or by gains of the short arm of chromosome 7 with a breakpoint near the EGFR gene locus, the minimal region of amplification mapping to EGFR, LANCL2, and SEC61G. No activating EGFR mutations were identified, suggesting that this is unlikely to be a common alternative underlying genetic mechanism for EGFR expression in metaplastic breast carcinomas. Given that metaplastic breast carcinomas are resistant to conventional chemotherapy or hormone therapy regimens and that tumours with EGFR amplification are reported to be sensitive to EGFR tyrosine kinase inhibitors, these findings indicate that further studies are warranted to explore EGFR tyrosine kinase inhibitors as potential therapeutic agents for metaplastic breast carcinomas harbouring amplification of 7p11.2.

Breast Neoplasms↗
PubMed2004

Is the pelvic organ prolapse quantification system (POPQ) being used? A survey of members of the International Continence Society (ICS) and the American Urogynecologic Society (AUGS).

The authors performed a web-based questionnaire survey of 667 members of the ICS and AUGS to determine the current use of the pelvic organ prolapse quantification (POPQ) system by members of the professional societies which have advocated its use. Three hundred and eighty (57%) gynecologists responded. This international survey shows that only 40.2% of ICS and AUGS members who responded routinely use the POPQ system in their clinical practice and provides information on the most common reasons for not using it. The results highlight some of the concerns regarding the complex nature of the system and its acceptance and use by specialists worldwide. It also suggests the need for a simplified version of the classification system that is user-friendly and can be adopted by all practitioners.

Female↗
PubMed2004

Management of cor triatriatum dexter by balloon dilatation in three dogs.

Two dogs, one immature and one adult, were presented with a history of progressive ascites. In a third, immature dog, increasing exercise intolerance had been noted. Echocardiography demonstrated a partition in the right atrium (cor triatriatum dexter) and echocontrast studies documented normal flow from the cranial vena cava into the right atrium and ventricle. A saphenous vein contrast study demonstrated flow from the caudal vena cava into an accessory right atrial chamber (sinus venarum). The sinus venarum communicated with the true right atrium via a small defect in the atrial membrane in one dog, and additionally with the left atrium via a right-to-left shunting foramen ovale in the other dogs. All defects were visualised on angiographic studies by selective catheterisation of the caudal vena cava via the femoral vein. Balloon dilatation of the defect was then performed using a small followed by a larger balloon angioplasty catheter to enlarge the defect in the atrial membrane. Clinical signs improved within days and were sustained in the long-term in all cases.

Animals↗
PubMed2004

Calculophagia?

Explore the source record for details and available documents.

Deglutition Disorders↗
PubMed2003

A new once-daily formulation of tolterodine provides superior efficacy and is well tolerated in women with overactive bladder.

This study evaluated the efficacy and tolerability of new extended-release (ER) tolterodine for the treatment of overactive bladder in women. In this subpopulation analysis of a double-blind multicenter trial, 1235 female patients were randomized to oral therapy with tolterodine ER 4 mg once daily (n=417), tolterodine IR 2 mg twice daily (n=408) or placebo (n=410) for 12 weeks. Both formulations reduced the mean number of urge incontinence episodes per week (both P=0.001 vs placebo); tolterodine ER was more effective than tolterodine IR (P=0.036). Both formulations significantly improved all other micturition chart variables compared to placebo. Dry mouth was the most common adverse event. There were no safety concerns. Toltrodine ER 4 mg once daily is effective and well tolerated in the treatment of women with overactive bladder, and reduces urge incontinence episodes more than the existing IR twice-daily formulation.

Benzhydryl Compounds↗
PubMed2003

Treatment of toxic epidermal necrolysis with intravenous immunoglobulin.

Toxic epidermal necrolysis (TEN) is a rare severe reaction of the skin resulting in full thickness damage to the epidermis. The condition has significant morbidity as a result of dehydration, protein loss, thermoregulatory difficulties, and renal, lung, liver and heart failure. The mortality rate approaches 30%, most commonly from bacterial sepsis. Management of this condition is cessation of the suspected causative agent and supportive care on a burns or intensive care unit. There have been recent reports of treatment using intravenous immunoglobulin (IVIG) therapy, though its efficacy is yet to be established. It has been proposed that IVIG inhibits the Fas-FasL mediated apoptosis of keratinocytes affected by TEN. We describe a case of extensive drug-induced TEN in a 33-year-old woman who showed rapid improvement with IVIG therapy at a dose of 0.75 g/kg/day given for four consecutive days.

Adult↗
PubMed2001

Mutation in Brca2 stimulates error-prone homology-directed repair of DNA double-strand breaks occurring between repeated sequences.

Mutation of BRCA2 causes familial early onset breast and ovarian cancer. BRCA2 has been suggested to be important for the maintenance of genome integrity and to have a role in DNA repair by homology- directed double-strand break (DSB) repair. By studying the repair of a specific induced chromosomal DSB we show that loss of Brca2 leads to a substantial increase in error-prone repair by homology-directed single-strand annealing and a reduction in DSB repair by conservative gene conversion. These data demonstrate that loss of Brca2 causes misrepair of chromosomal DSBs occurring between repeated sequences by stimulating use of an error-prone homologous recombination pathway. Furthermore, loss of Brca2 causes a large increase in genome-wide error-prone repair of both spontaneous DNA damage and mitomycin C-induced DNA cross-links at the expense of error-free repair by sister chromatid recombination. This provides insight into the mechanisms that induce genome instability in tumour cells lacking BRCA2.

Alleles↗
PubMed2001

Quorum sensing as a population-density-dependent determinant of bacterial physiology.

The discovery that bacterial cells can communicate with each other has led to the realization that bacteria are capable of exhibiting much more complex patterns of co-operative behaviour than would be expected for simple unicellular microorganisms. Now generically termed 'quorum sensing', bacterial cell-to-cell communication enables a bacterial population to mount a unified response that is advantageous to its survival by improving access to complex nutrients or environmental niches, collective defence against other competitive microorganisms or eukaryotic host defence mechanisms and optimization of population survival by differentiation into morphological forms better adapted to combating environmental threats. The principle of quorum sensing encompasses the production and release of signal molecules by bacterial cells within a population. Such molecules are released into the environment and, as cell numbers increase, so does the extracellular level of signal molecule, until the bacteria sense that a threshold has been reached and gene activation, or in some cases depression or repression, occurs via the activity of sensor-regulator systems. In this review, we will describe the biochemistry and molecular biology of a number of well-characterized N-acylhomoserine lactone quorum sensing systems to illustrate how bacteria employ cell-to-cell signalling to adjust their physiology in accordance with the prevailing high-population-density environment.

4-Butyrolactone↗
PubMed2001

Quorum sensing as an integral component of gene regulatory networks in Gram-negative bacteria.

Bacterial cell-to-cell communication (quorum sensing) relies upon the interaction of a small diffusible signal molecule with a sensor or transcriptional activator to couple gene expression with cell population density. In Gram-negative bacteria, it is now clear that N-acylhomoserine lactones bind directly to LuxR homologues and can be synthesized via one of three unrelated bacterial protein families and by transgenic plants. New chemical classes of signal molecules have been identified, some of which exhibit crosstalk with N-acylhomoserine-lactone-mediated quorum sensing. As the determinant of cell population density, quorum sensing is emerging as an integral component of bacterial global gene regulatory networks responsible for facilitating bacterial adaptation to environmental stress. N-acylhomoserine lactones are produced during experimental animal and human infections, and a function beyond quorum sensing has been suggested by their intrinsic immunomodulatory and pharmacological activities.

Gene Expression Regulation, Bacterial↗
PubMed2001

Supplementation of islet culture medium with insulin may have a beneficial effect on islet secretory function.

Recent reports suggest that apoptosis resulting from the disruption of the normal cell-matrix relationship (anoikis) during islet isolation could lead to a loss of islet tissue in culture. Insulin is known to have a role in cell growth and survival, and this study was undertaken to assess any beneficial effect on islets by supplementing the islet culture medium with insulin. Human and porcine islets were cultured in medium supplemented with 0, 10, 100, and 1,000 ng x mL(-1) insulin. Secretory function was assessed by perifusion at days 1 and 8. The results demonstrated a significant variation in stimulation index between isolations for human islets, but there was no effect relating to the concentration of insulin in the medium or time in culture. For porcine islets, there was a significant (p < 0.001) improvement in secretory function for islets cultured in 10 and 100 ng x mL(-1) insulin, relative to 0 and 1,000 ng x mL(-1) insulin. There was no interisolation variation or effect of time in culture. In conclusion, the secretory function of porcine islets benefited from the addition of 10 to 100 ng x mL(-1) insulin to the culture medium, but interisolation variation in human islet secretory function did not allow any specific effect of the insulin to be determined.

Animals↗
PubMed2001

SdiA of Salmonella enterica is a LuxR homolog that detects mixed microbial communities.

Proteins of the LuxR family detect the presence of N-acylhomoserine lactones (AHLs) and regulate transcription accordingly. When AHLs are synthesized by the same species that detects them, the system allows a bacterium to measure the population density of its own species, a phenomenon known as quorum sensing. The sdiA genes of Escherichia coli and Salmonella enterica serovar Typhimurium are predicted to encode LuxR homologs. However, these species do not appear to synthesize AHLs or any other molecule detected by SdiA. It has previously been demonstrated that overexpression of sdiA results in the activation of the ftsQAZ locus in E. coli and four other loci in Salmonella serovar Typhimurium. Here we report that transcriptional fusions to these five loci fall into two classes. The first class requires overexpression of sdiA for activation. The second class responds to sdiA expressed from its natural position in the chromosome if the appropriate AHLs are added to the culture. The only member of the second class is a series of Prck-luxCDABE fusions in Salmonella serovar Typhimurium. SdiA responds with highest sensitivity to AHLs that have a keto modification at the third carbon and an acyl chain length of 6 or 8 (half-maximal response between 1 and 5 nM). Growth of Salmonella in proximity to species known to synthesize these AHLs results in sdiA-dependent activation of the Prck-luxCDABE fusions. SdiA appears to be the first AHL receptor discovered that detects signals emanating exclusively from other species.

4-Butyrolactone↗
PubMed2001

Strictures of the sigmoid colon: barium enema evaluation.

PURPOSE: To assess the accuracy of radiologic interpretation, in the absence of clinical information, in the differentiation of benign and malignant sigmoid strictures at barium enema examination. MATERIALS AND METHODS: On two occasions, four independent observers retrospectively assessed examination findings in 78 patients with documented sigmoid strictures (43 benign, 35 malignant). Each stricture was graded by using a five-point scale (definitely malignant to definitely benign). RESULTS: No significant difference existed between the areas under the receiver operating characteristic curves for the two assessments with any observer. Consensus findings indicated agreement among at least three of the four observers in 68 (87%) and 66 (85%) cases at the first and second assessments, respectively. One benign stricture was called malignant at both assessments. When consensus existed, the positive predictive value for malignant strictures was 96% at both assessments (sensitivity, 63% and 66%). Nine malignant strictures were called benign, three at both assessments. When consensus existed, the positive predictive value for benign strictures was 84% and 88% at the first and second assessments, respectively (sensitivity, 88% and 86%, respectively). CONCLUSION: The differentiation between a benign and a malignant sigmoid stricture can be made in most cases at barium enema examination. When a stricture appears malignant, the diagnosis is usually correct, but caution is advised when a stricture appears benign.

Adult↗
PubMed2000

Quorum sensing and the population-dependent control of virulence.

One crucial feature of almost all bacterial infections is the need for the invading pathogen to reach a critical cell population density sufficient to overcome host defences and establish the infection. Controlling the expression of virulence determinants in concert with cell population density may therefore confer a significant survival advantage on the pathogen such that the host is overwhelmed before a defence response can be fully initiated. Many different bacterial pathogens are now known to regulate diverse physiological processes including virulence in a cell-density-dependent manner through cell-cell communication. This phenomenon, which relies on the interaction of a diffusible signal molecule (e.g. an N-acylhomoserine lactone) with a sensor or transcriptional activator to couple gene expression with cell population density, has become known as 'quorum sensing'. Although the size of the 'quorum' is likely to be highly variable and influenced by the diffusibility of the signal molecule within infected tissues, nevertheless quorum-sensing signal molecules can be detected in vivo in both experimental animal model and human infections. Furthermore, certain quorum-sensing molecules have been shown to possess pharmacological and immunomodulatory activity such that they may function as virulence determinants per se. As a consequence, quorum sensing constitutes a novel therapeutic target for the design of small molecular antagonists capable of attenuating virulence through the blockade of bacterial cell-cell communication.

4-Butyrolactone↗
PubMed2000

PAR1 thrombin receptor-G protein interactions. Separation of binding and coupling determinants in the galpha subunit.

Signal transfer between the protease-activated PAR1 thrombin receptor and membrane-associated heterotrimeric G proteins is mediated by protein-protein interactions. We constructed a yeast signaling system that resolves domain-specific functions of binding from coupling in the Galpha subunit. The endogenous yeast Galpha subunit, Gpa1, does not bind to PAR1 and served as a null structural template. N- and C-terminal portions of mammalian G(i2) and G(16) were substituted back into the Gpa1 template and gain-of-function assessed. The C-terminal third of G(16), but not of G(i2), provides sufficient interactions for coupling to occur with PAR1. The N-terminal two-thirds of G(i2) also contains sufficient determinants to bind and couple to PAR1 and overcome the otherwise negative or missing interactions supplied by the C-terminal third of Gpa1. Replacement of the N-terminal alpha-helix of G(i2), residues 1-34, with those of Gpa1 abolishes coupling but not binding to PAR1 or to betagamma subunits. These data support a model that the N-terminal alphaN helix of the Galpha subunit is physically interposed between PAR1 and the Gbeta subunit and directly assists in transferring the signal between agonist-activated receptor and G protein.

Amino Acid Sequence↗
PubMed1999

FXY2/MID2, a gene related to the X-linked Opitz syndrome gene FXY/MID1, maps to Xq22 and encodes a FNIII domain-containing protein that associates with microtubules.

Opitz G/BBB syndrome (OS) is a genetically heterogeneous disorder with an X-linked locus and an autosomal locus linked to 22q11.2. OS affects multiple organ systems with often variable severity even between siblings. The clinical features, which include hypertelorism, cleft lip and palate, defects of cardiac septation, hypospadias, and anorectal anomalies, indicate an underlying disturbance of the developing ventral midline of the embryo. The gene responsible for X-linked OS, FXY/MID1, is located on the short arm of the human X chromosome within Xp22.3 and encodes a protein with both an RBCC (RING finger, B-box, coiled coil) and a B30.2 domain. The Fxy gene in mice is also located on the X chromosome but spans the pseudoautosomal boundary in this species. Here we describe a gene closely related to FXY/MID1, called FXY2, which also maps to the X chromosome within Xq22. The mouse Fxy2 gene is located on the distal part of the mouse X chromosome within a region syntenic to Xq22. Analysis of genes flanking both FXY/MID1 and FXY2 (as well as their counterparts in mouse) suggests that these regions may have arisen as a result of an intrachromosomal duplication on an ancestral X chromosome. We have also identified in both FXY2 and FXY/MID1 proteins a conserved fibronectin type III domain located between the RBCC and B30.2 domains that has implications for understanding protein function. The FXY/MID1 protein has previously been shown to colocalize with microtubules, and here we show that the FXY2 protein similarly associates with microtubules in a manner that is dependent on the carboxy-terminal B30.2 domain.

Abnormalities, Multiple↗