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Biomedical subjects

M Warner

Publications and source records attributed to M Warner.

At least 55 records · Page 3Linked to original sources
PubMed2003

Survey of resistance of Pseudomonas aeruginosa from UK patients with cystic fibrosis to six commonly prescribed antimicrobial agents.

BACKGROUND: Respiratory infection with Pseudomonas aeruginosa is very common in patients with cystic fibrosis (CF) but antimicrobial resistance rates of CF isolates across the UK are largely unknown. METHODS: The susceptibility of 417 CF patient isolates of P aeruginosa from 17 hospitals to six commonly prescribed antibiotics were examined. Isolates were tested by an agar break point dilution method and E-tests according to British Society of Antimicrobial Chemotherapy guidelines. Genotyping of isolates was performed by XbaI DNA macrorestriction and pulsed field gel electrophoresis. RESULTS: 38% of isolates were susceptible to all of the agents tested; almost half were resistant to gentamicin compared with ceftazidime (39%), piperacillin (32%), ciprofloxacin (30%), tobramycin (10%), and colistin (3%). Approximately 40% were resistant to two or more compounds with ceftazidime in combination with gentamicin, piperacillin or ciprofloxacin being the most common cross resistances. Resistance rates were generally similar to those reported recently from the USA and Germany. A selection of resistant isolates proved to be predominantly genotypically distinct by XbaI DNA macrorestriction but six pairs from three centres had similar genotypes. CONCLUSIONS: The level of resistance to front line antipseudomonal agents, with the exception of colistin, is disturbingly high. The prudent use of antimicrobial drugs and closer monitoring of accumulation of resistant strain populations should be actively considered.

Adult↗
PubMed2003

Reflectivity of cholesteric liquid crystals with spatially varying pitch.

Solids with spatially varying photonic structure offer gaps to light of a wider range of frequencies than do simple photonic systems. We solve numerically the field distribution in a cholesteric with a linearly varying inverse pitch (helical wavevector) using equations we derive for the general case. The simple idea that the position where the Bragg condition is locally satisfied is where reflection takes place is only true in part. Here, reflection is due to a region where the waves are forced to become evanescent, and the rate of variation of structure determines over which distance the waves decay and therefore how complete reflection is. The approximate local Bragg-de Vries schemes are shown to break down in detail at the edges of the gap, and an analytical estimate is given for the transmission coefficient.

Cholesterol↗
PubMed2002

Emerging linezolid-resistant Enterococcus faecalis and Enterococcus faecium isolated from two Austrian patients in the same intensive care unit.

Of two patients in the same intensive care unit who were treated with linezolid, one yielded linezolid-resistant Enterococcus faecalis, whereas the other yielded linezolid-resistant Enterococcus faecium. In each case, molecular typing indicated that the resistant isolates were related to linezolid-susceptible isolates from the same patient, but differed from them by the same G2576U ribosomal RNA mutation. This is the first clinical case report of emerging resistance to linezolid among Enterococcus faecalis and also the first report of resistance involving vancomycin-susceptible rather than vancomycin-resistant enterococci. The linezolid-resistant isolates showed cross-resistance to the experimental oxazolidinone AZD2563, suggesting that oxazolidinone resistance might be a class effect.

Acetamides↗
PubMed2002

Photonic band structure of cholesteric elastomers.

We calculate the photonic band structure along and oblique to the helix axis of cholesteric elastomers. They are highly deformable, self-assembling systems. They display brilliantly colored reflections and lasing owing to stop bands in their photonic band structure. This band structure varies sensitively and extensively with strain. We show how additional stop bands open up and how they all shift in frequency. We predict a "total" stop band, that is, for both circular polarizations and show analytically how stop bands scale with strain. The extension of stop bands to a range of angles thereby creates pseudogaps, and the relevance to low-threshold lasing is discussed.

Journal Article↗
PubMed2002

Uniaxial and biaxial soft deformations of nematic elastomers.

We give a geometric interpretation of the soft elastic deformation modes of nematic elastomers, with explicit examples, for both uniaxial and biaxial nematic order. We show the importance of body rotations in this nonclassical elasticity and how the invariance under rotations of the reference and target states gives soft elasticity (the Golubovic and Lubensky theorem). The role of rotations makes the polar decomposition theorem vital for decomposing general deformations into body rotations and symmetric strains. The role of the square roots of tensors and that of finding explicit forms for soft deformations (the approach of Olmsted) are discussed in this context.

Journal Article↗
PubMed2002

Estrogen receptor beta in breast cancer.

Estrogen is essential for normal growth and differentiation in the mammary gland. It also supports growth of approximately 50% of primary breast cancers. For this reason, removal of estrogen or blocking of its action with the anti-estrogen, tamoxifen, is the main treatment for estrogen receptor alpha (ERalpha)-positive tumors. In 1996, when oncologists became aware of a second ER, ERbeta, there was some doubt as to whether this receptor would be of importance in breast cancer because the clinical consensus was that responsiveness to tamoxifen is related to the presence of ERalpha in breast cancer. Today we know that ERalpha and ERbeta have distinct cellular distributions, regulate separate sets of genes and can oppose each other's actions on some genes. We also know that ERbeta is widely expressed in both the normal and malignant breast and that there are proliferating cells in the breast which express ERbeta. In this review we summarize what is known about ERbeta in breast cancer and examine the possibility that ERbeta-selective ligands may well represent a useful class of pharmacological tools with a novel target, namely proliferating cells expressing ERbeta.

Animals↗
PubMed2001

Photonic band structure of highly deformable self-assembling systems.

We calculate the photonic band structure at normal incidence of highly deformable, self-assembling systems-cholesteric elastomers subjected to external stress. Cholesteric elastomers display brilliantly colored reflections and lasing owing to gaps in their photonic band structure. This band structure has been shown to vary sensitively with strain in both theory and experiment. New gaps open up and all gaps shift in frequency. We predict a different "total" band gap for all polarizations in the vicinity of the previously observed de Vries band gap, which is only for one polarization.

Journal Article↗
PubMed2001

Estrogen receptors and proliferation markers in primary and recurrent breast cancer.

To elucidate the clinical importance of estrogen receptor (ER) beta in breast cancer, 29 archival primary breast cancer specimens, six locally recurrent cancers, and five benign mammary tumors were examined histochemically for ERalpha, ERbeta and the proliferation markers Ki67 and cyclin A. In benign tumors, most epithelial cells contained ERbeta, but ERalpha was rare. In primary cancers, both ERalpha and ERbeta occurred in epithelial cells, the presence of ERbeta being associated with elevated expression of Ki67 and cyclin A, and ERalpha with decreased levels. Thus, the highest content of proliferation markers was seen in primary cancers that were ERalpha(-) ERbeta(+). Most Ki67-containing cells coexpressed ERbeta, but few showed ERalpha. In locally recurring cancers, ERalpha, ERbeta, and Ki67 were more highly expressed than in the corresponding primary tumors, and many cells containing ERbeta, but few with ERalpha, expressed Ki67. Surprisingly, ERbeta, but not ERalpha, was seen in the stromal cells of both primary and recurrent cancers. Because the response of breast cancers to tamoxifen therapy is correlated with the presence of ERalpha, cancer cells that lack ERalpha but contain ERbeta and proliferation markers represent a novel population of apparently proliferating cells that probably are not targeted by the current antiestrogens. Thus, appropriate ERbeta-specific ligands, perhaps in combination with tamoxifen, may be useful in improving the treatment of breast cancers.

Biomarkers, Tumor↗
PubMed2001

Cholesteric elastomers: deformable photonic solids.

A mechanical strain applied to a monodomain cholesteric elastomer modulates and eventually unwinds the helical director distribution. There are similarities with the classical problem of an electric field applied to a cholesteric liquid crystal, but also differences. Frank elasticity is of minor importance unless the gel is very weak. The interplay is rather between the director being helically anchored to the rubber elastic matrix and the external mechanical field. Stretching perpendicular to the helix axis induces the uniform unwound state via the elimination of sharp, pinned twist walls above a critical strain. Below the critical strain the coarsening of the director distribution is not accompanied by an increase but rather by an affine decrease in the pitch. Unwinding through conical director states occurs when the elastomer is stretched along the helical axis. Finally we consider cholesteric elastomers in a classical device geometry with an electric field applied along the pitch axis and hence transverse to the director orientation.

Journal Article↗
PubMed2001

Expression, function, and clinical implications of the estrogen receptor beta in human lung cancers.

The higher frequency of human lung adenocarcinoma in females than in males, strongly suggests the involvement of gender dependent factors in the etiology of this disease. This is the first investigation of estrogen receptor (ER) beta in human lung. Immunohistochemical staining revealed ERbeta expression in normal lung and in atypical adenomatous hyperplasia (AAH), considered as a precancerous lesion for adenocarcinomas. Adenocarcinomas showed significantly higher expression of ERbeta than squamous cell carcinomas. On the contrary, ERalpha expression was not detected in all cases. The functional integrity of ERbeta such as the binding ability to estrogen responsive element (ERE) and transcriptional activity was confirmed using a human lung cancer cell line, RERF-LC-OK. Colony formation of this cell was significantly reduced in the presence of pure antiestrogen. We conclude that ERbeta, but not ERalpha, is present in lung tissues with an important physiological function in normal lung. Furthermore, ERbeta may play a role in growth and development of adenocarcinomas.

Adenocarcinoma↗
PubMed2001

A new opto-mechanical effect in solids.

We propose that large, reversible shape changes in solids, of between 10%-400%, can be induced optically by photoisomerizing monodomain nematic elastomers. Empirical and molecular analysis of shape change and its relation to thermal effects is given along with a simple model of the dynamics of response. Our experiments demonstrate these effects for the first time and theory is compared qualitatively with our results.

Journal Article↗
PubMed2001

Imprinted networks as chiral pumps.

We investigate the interaction between a chirally imprinted network and a solvent of chiral molecules. We find that a liquid-crystalline polymer network is preferentially swollen by one component of a racemic solvent. This ability to separate is linked to the chiral order parameter of the network, and can be reversibly controlled via temperature or a mechanical deformation. It is maximal near the point at which the network loses its imprinted structure. One possible practical application of this effect would be a mechanical device for sorting mixed chiral molecules.

Models, Chemical↗
PubMed2001

A role for estrogen receptor beta in the regulation of growth of the ventral prostate.

In normal rats and mice, immunostaining with specific antibodies revealed that nuclei of most prostatic epithelial cells harbor estrogen receptor beta (ERbeta). In rat ventral prostate, 530- and 549-aa isoforms of the receptor were identified. These sediment in the 4S region of low-salt sucrose gradients, indicating that prostatic ERbeta does not contain the same protein chaperones that are associated with ERalpha. Estradiol (E(2)) binding and ERbeta immunoreactivity coincide on the gradient, with no indication of ERalpha. In prostates from mice in which the ERbeta gene has been inactivated (BERKO), androgen receptor (AR) levels are elevated, and the tissue contains multiple hyperplastic foci. Most epithelial cells express the proliferation antigen Ki-67. In contrast, prostatic epithelium from wild-type littermates is single layered with no hyperplasia, and very few cells express Ki-67. Rat ventral prostate contains an estrogenic component, which comigrates on HPLC with the testosterone metabolite 5alpha-androstane-3beta,17beta-diol (3betaAdiol). This compound, which competes with E(2) for binding to ERbeta and elicits an estrogenic response in the aorta but not in the pituitary, decreases the AR content in prostates of wild-type mice but does not affect the elevated levels seen in ERbeta knockout (BERKO) mice. Thus ERbeta, probably as a complex with 3betaAdiol, is involved in regulating the AR content of the rodent prostate and in restraining epithelial growth. These findings suggest that ligands specific for ERbeta may be useful in the prevention and/or clinical management of prostatic hyperplasia and neoplasia.

Androstane-3,17-diol↗
PubMed2001

Anomalous viscoelastic response of nematic elastomers.

We report a combined theoretical and experimental study of linear viscoelastic response in oriented monodomain nematic elastomers. The model predicts a dramatic decrease in the dynamic modulus in certain deformation geometries in an elastic medium with an independently mobile internal degree of freedom, the nematic director with its own relaxation dynamics. Dynamic mechanical measurements on monodomain nematic elastomers confirm our predictions of dependence on shear geometry and on nematic order, and also show a very substantial mechanical loss clearly associated with director relaxation.

Journal Article↗
PubMed2001

Morphological abnormalities in the brains of estrogen receptor beta knockout mice.

Estrogen receptor beta (ERbeta) is expressed at high levels in both neurons and glial cells of the central nervous system. The development of ERbeta knockout (BERKO) mice has provided a model to study the function of this nuclear receptor in the brain. We have found that the brains of BERKO mice show several morphological abnormalities. There is a regional neuronal hypocellularity in the brain, with a severe neuronal deficit in the somatosensory cortex, especially layers II, III, IV, and V, and a remarkable proliferation of astroglial cells in the limbic system but not in the cortex. These abnormalities are evident as early as 2 mo of age in BERKO mice. As BERKO mice age, the neuronal deficit becomes more pronounced, and, by 2 yr of age, there is degeneration of neuronal cell bodies throughout the brain. This is particularly evident in the substantia nigra. We conclude that ERbeta is necessary for neuronal survival and speculate that this gene could have an important influence on the development of degenerative diseases of the central nervous system, such as Alzheimer's disease and Parkinson's disease, as well as those resulting from trauma and stroke in the brain.

Animals↗
PubMed2001

Validation study of nonsurgical diagnosis of endometriosis.

OBJECTIVE: To determine whether the surgical diagnosis of endometriosis can be predicted using symptoms, signs, and ultrasound findings. DESIGN: Prospective study (study sample); retrospective record review (test sample). SETTING: Hospital of Desio (study sample) and Mangiagalli Hospital (test sample), Italy. PATIENT(S): Ninety women scheduled to undergo laparoscopy or laparotomy (study sample); 120 women who underwent laparoscopy (test sample). INTERVENTION: The study sample group was interviewed before surgery about infertility and dysmenorrhea, dyspareunia, and noncyclic pelvic pain and each member had a pelvic examination and a transvaginal ultrasound. At surgery, endometriosis was noted. For the test sample, the same information was abstracted from medical records after laparoscopy. MAIN OUTCOME MEASURE(S): The ability of symptoms, signs, and ultrasound to predict endometriosis at surgery. A classification tree was developed with the study sample and evaluated with the test sample. RESULT(S): Ovarian endometriosis, but not nonovarian endometriosis, could be reliably predicted with noninvasive tools. Ultrasound and examination best predicted ovarian endometriosis, correctly classifying 100% of cases with no false positive diagnoses in the study sample. Similar results were found in the test sample. CONCLUSION(S): Noninvasive tools may be used to identify women with ovarian, but not nonovarian endometriosis, with excellent agreement with surgical diagnosis.

Adult↗