First Report of the HLA-DQB1*03:575 Allele in a Kidney Transplant Recipient of European Descent.
The new HLA-DQB1*03:575 differs from HLA-DQB1* 03:03:02:01 by a single base substitution at exon 2.
Humans↗
Biomedical subjects
A Sharma
Publications and source records attributed to A Sharma.
Fluoxetine treatment increases trabecular bone formation in mice.
Mounting evidence exists for the operation of a functional serotonin (5-HT) system in osteoclasts and osteoblasts, which involves both receptor activation and 5-HT reuptake. In previous work we showed that the serotonin transporter (5-HTT) is expressed in osteoclasts and that its activity is required by for osteoclast differentiation in vitro. The purpose of the current study was to determine the effect of treatment with fluoxetine, a specific serotonin reuptake inhibitor, on bone metabolism in vivo. Systemic administration of fluoxetine to Swiss-Webster mice for 6 weeks resulted in increased trabecular BV and BV/TV in femurs and vertebrae as determined by micro-computed tomography (microCT). This correlated with an increase in trabecular number, connectivity, and decreased trabecular spacing. Fluoxetine treatment also resulted in increased volume in vertebral trabecular bone. However, fluoxetine-treated mice were not protected against bone loss after ovariectomy, suggesting that its anabolic effect requires the presence of estrogen. The effect of blocking the 5-HTT on bone loss following an LPS-mediated inflammatory challenge was also investigated. Subcutaneous injections of LPS over the calvariae of Swiss-Webster mice for 5 days resulted in increased numbers of osteoclasts and net bone loss, whereas new bone formation and a net gain in bone mass was seen when LPS was given together with fluoxetine. We conclude that fluoxetine treatment in vivo leads to increased bone mass under normal physiologic or inflammatory conditions, but does not prevent bone loss associated with estrogen deficiency. These data suggest that commonly used anti-depressive agents may affect bone mass.
Animals↗
Analgesic efficacy of single-dose parecoxib for corneal suturing in children.
Explore the source record for details and available documents.
Adolescent↗
Changes in gene expression in beta cells after islet isolation and transplantation using laser-capture microdissection.
AIMS/HYPOTHESIS: The process of islet isolation can cause chemical and mechanical injury to beta cells. In addition, hyperglycaemia after islet transplantation can compromise beta cell function. The aim of this experiment was to evaluate changes in gene expression in endogenous islets using laser-capture microdissection (LCM). MATERIALS AND METHODS: Islets from B6AF1 mice were studied in situ in the pancreas as well as those freshly isolated or cultured for 24 h. Fresh islets were transplanted under the kidney capsule of syngeneic diabetic (streptozocin-induced) and non-diabetic mice. Frozen sections from all the samples were prepared for LCM to obtain beta cell-enriched tissue; RNA was extracted and amplified using T7 polymerase. RT-PCR was used to assess expression of selected genes critical for beta cell function (Ins, Ipf1 [previously known as Pdx1], Slc2a2 [previously known as GLUT2] and Ldha) and the stress response (Hmox1 [previously known as HO-1], Gpx1, Tnfaip3 [previously known as A20] and Fas). Immunostaining was also performed. RESULTS: In freshly isolated and cultured islets, insulin and Ipf1 mRNA levels were decreased by 40% (compared with islets in situ), while stress genes were upregulated. Comparison between in situ pancreatic islets and engrafted beta cells of cured mice showed declines in Ipf1 expression. CONCLUSIONS/INTERPRETATION: Our experiment, the first report to investigate changes in gene expression in endogenous islets using LCM, indicate that beta cells following islet isolation and residing in a foreign graft environment have decreased expression of genes involved in insulin production and increased expression of stress genes. Our data suggest that an islet graft, even in successful transplantation, may be different from endogenous islets in gene expression.
Animals↗
ArrayExpress--a public database of microarray experiments and gene expression profiles.
UNLABELLED: ArrayExpress is a public database for high throughput functional genomics data. ArrayExpress consists of two parts--the ArrayExpress Repository, which is a MIAME supportive public archive of microarray data, and the ArrayExpress Data Warehouse, which is a database of gene expression profiles selected from the repository and consistently re-annotated. Archived experiments can be queried by experiment attributes, such as keywords, species, array platform, authors, journals or accession numbers. Gene expression profiles can be queried by gene names and properties, such as Gene Ontology terms and gene expression profiles can be visualized. ArrayExpress is a rapidly growing database, currently it contains data from >50,000 hybridizations and >1,500,000 individual expression profiles. ArrayExpress supports community standards, including MIAME, MAGE-ML and more recently the proposal for a spreadsheet based data exchange format: MAGE-TAB. AVAILABILITY: www.ebi.ac.uk/arrayexpress.
Animals↗
Methicillin resistant Staphylococcus aureus: is it a problem for nasal surgery?
Methicillin resistant Staphylococcus aureus (MRSA) is becoming ever more prevalent in the UK, and the proportion of MRSA to methicillin sensitive Staphylococcus aureus (MSSA) seems to be increasing. New strains of MRSA are ever developing resistance to antibiotic treatment, increasing morbidity and mortality of infection. Staphylococcus aureus is part of the normal flora of the nose, and MRSA colonizes the nose in infection. However, nasal surgery is rarely complicated by staphylococcal infections, and MRSA infection following nasal surgery is rare. The authors present a literature review of MRSA infection, its relation to the nasal cavity, and infection following nasal surgery.
Carrier State↗
Analysis of 2167 head and neck cancer patients' management, treatment compliance and outcomes from a regional cancer centre, Delhi, India.
Head and neck cancer care was analysed in 2167 unselected patients for management compliance and outcome. Median age was 55 years, with a male to female ratio of 5.5ratio1. Major sites were oropharynx (32.4 per cent), larynx (19.8 per cent), oral (16.6 per cent) and hypopharynx (12.9 per cent). Stage-wise distribution was I-II=8.9 per cent, III=20.6 per cent and IV=60.3 per cent and unstaged=10.2 per cent. Squamous cell carcinoma was the dominant histology for 90.9 per cent. Clinic-based cancer-directed treatment decisions were made for 1905 patients: curative intent in 53 per cent, palliative in 35 per cent and for the remaining 262 (12 per cent) supportive care. Overall, 1209 (56 per cent) patients complied with the prescribed treatments; 62 per cent, 54 per cent, and 35 per cent of curative, palliative and supportive care intent groups, respectively. Modalities were radiotherapy alone (64.6 per cent), combined surgery with irradiation (17.6 per cent), and chemoradiotherapy (11.2 per cent). Median follow-up periods were 17.5 and three months in curative and palliative groups respectively. Overall, 712 (33 per cent) cases received curative therapy, with three-year disease-specific survival of 49 per cent. Patient compliance was a major obstacle. The comparison of this series with the USA, Canada and Norway showed wide disparities in stage of presentation and survival.
Adolescent↗
Fabrication and characterization of a diffraction-grating transducer in thin polybutadiene rubber film for sensing dynamical strain.
Surface relief gratings are holographically fabricated in thin polybutadiene rubber films produced by both spin coating and dip coating on glass and metal substrates. These thin-film gratings are characterized for their application as efficient transducers for detecting dynamic strain in solids. The performance of these rubber-grating transducers is compared to surface-mounted fiber Bragg gratings for a range of frequencies between 50 Hz and 30 kHz. Dynamic-strain sensitivity around 1 nepsilon/radicalHz is recorded for thin rubber-film grating transducers.
Journal Article↗
Photopatterning in poly-L-lysine thin films using UV-enhanced hydrophilicity.
Deep UV lithography on poly-L-lysine thin films was used to generate microarrays with enhanced hydrophilicity. This was manifested as adsorption of ambient humidity from air by areas exposed to UV fluence around 5 J/cm2 and was made visible by phase-contrast microscopy. Kinetics of adsorption was investigated by a novel technique involving fabrication of submicrometer hydrophilicity grating by two-beam UV interferometry. In an aqueous colloidal medium, gold and polystyrene microspheres preferentially attach to areas that are relatively less hydrophilic, i.e., those areas not exposed to UV light. This observation provides a method for fabricating micro- and nanoporous arrays with controlled porosity. The technique is demonstrated with microspheres of sizes between 250 nm and 10 microm.
Adsorption↗
Is undergraduate otorhinolaryngology teaching relevant to junior doctors working in accident and emergency departments?
Undergraduate ENT teaching provides junior doctors with skills and knowledge useful for the practice of medicine. However, ENT has been removed from the curriculum of nine of the 29 medical schools in the United Kingdom, as it was not deemed relevant to general medical practice. A telephone survey was performed of 20 senior house officers working in accident and emergency (A&E) departments across the United Kingdom. The results showed that 90 per cent felt their undergraduate ENT teaching was directly beneficial to working in A&E, 75 per cent felt they had not received enough undergraduate ENT teaching and 45 per cent currently received no postgraduate teaching whilst working in A&E. These results illustrate the importance of ENT teaching in the undergraduate curriculum and its value to practising doctors. They highlight the fact that prospective studies are required to examine the effect on junior doctors of changing the curriculum.
Attitude of Health Personnel↗
Postmenopausal women undergoing transvaginal ultrasound screening prefer not to have chaperones.
The Royal College of Radiologists has recommended chaperones of the appropriate gender for those undergoing intimate scans. This has significant implications for clinical and research programmes. Two hundred and fifty women undergoing scanning in a screening trial were sent postal questionnaires to determine their views as to the presence of chaperones and the gender of ultrasonographers. Ninety-five percent of 198 women stated that they would not like another person to be present during transvaginal scanning. Of greater consequence to women was the gender of the ultrasonographer, with 83.3% expressing a preference for a female ultrasonographer. This needs to be considered in making decisions about allocation of scarce resources.
Aged↗
Podophyllum hexandrum Offers Radioprotection by Modulating Free Radical Flux: Role of Aryl-Tetralin Lignans.
We have evaluated the effect of variation in aryl-tetralin lignans on the radioprotective properties of Podophyllum hexandrum. Two fractionated fractions of P. hexandrum [methanolic (S1) and chloroform fractions (S2)], with varying aryl-tetralin lignan content were utilized for the present study. The peroxyl ion scavenging potentials of S1 and S2 were found to be comparable [i.e. 45.88% (S1) and 41% (S2)] after a 48 h interval in a time-dependent study, whereas in a 2 h study, S2 exhibited significant (P < 0.05) antioxidant activity in different metal ion + flux states. In the aqueous phase, S2 exhibited non-site-specific reactive oxygen species scavenging activity, i.e. 73.12% inhibition at 500 mug ml(-1). S1 exhibited 58.40 +/- 0.8% inhibition (at 0.025 mug ml(-1)) of the formation of reactive nitrite radicals, comparable to S2 (52.45 +/- 0.825%), and also showed 45.01% site-specific activity (1000 mug ml(-1)), along with significant (P < 0.05) electron donation potential (50-2000 mug ml(-1)) compared to S2. Such activities of S1 could be attributed to the significantly (P < 0.05) higher levels of podophyllotoxin beta-d-glucopyranoside (16.5 times) and demethyl podophyllotoxin glucoside (2.9 times) compared with S2. Together, these findings clearly prove that aryl-tetralin lignan content influences the radiation protective potential of the Podophyllum fractions to a great extent.
Journal Article↗
Instability and dynamics of thin viscoelastic liquid films.
The instability, rupture, and subsequent growth of holes in a thin Jeffreys-type viscoelastic film under the influence of long-range van der Waals force are investigated using both linear stability analysis and nonlinear numerical solutions. The linear stability analysis of full governing equations valid for arbitrary wave numbers shows that although fluid rheology does not influence the dominant length scale of the instability, it significantly affects the growth rate. It is shown that neglect of inertia and solvent dynamics results in a nonphysical singularity in the growth rate beyond a critical value of relaxation time. We further carry out numerical simulations of a set of long-wave, nonlinear differential equations (also derived in Rauscher et al., Eur. Phys. J. E 17, 373 (2005)) governing the evolution of the free surface. The nonlinear simulations, in their domain of validity, confirm the results of the linear analysis. Interestingly, results from nonlinear simulations further show that both for Newtonian and viscoelastic liquids, the shape and the dewetting dynamics of a hole are identical when examined in terms of a rescaled time which depends on rheological parameters. Thus, viscoelasticity of Jeffreys type merely accelerates the growth rate, without however affecting the important morphological characteristics.
Computer Simulation↗
Oxidative stress markers and antioxidant levels in normal pregnancy and pre-eclampsia.
OBJECTIVE: To compare the levels of 3 oxidative stress markers (glutathione peroxidase [GPX], superoxide dismutase [SOD], and malondialdehyde [MDA]) and 2 antioxidants (vitamin C and lycopene) in healthy and pre-eclamptic pregnant women. METHODS: Circulating levels of GPX, SOD, MDA, vitamin C and lycopene were measured in 50 healthy pregnant women and 50 women with pre-eclampsia (PE) (41 with mild PE and 9 with severe PE) attending the antenatal clinic or admitted to the maternity ward of the All-India Institute of Medical Sciences, New Delhi, India. RESULTS: The levels of GPX, SOD and MDA were significantly higher in women with PE than in controls, and the increase was higher in women with severe PE (P<0.001 using analysis of variance and the Kruskal Wallis test). The levels of vitamin C and lycopene were significantly lower in women with PE than in controls, with a greater decrease in women with severe PE. CONCLUSION: Increased levels of oxidative stress markers and decreased levels of antioxidants in pre-eclamptic women suggest that oxidative stress markers play a significant role in the pathophysiology of pre-eclampsia, and that supplemental dietary antioxidants may have a beneficial role in the prevention of pre-eclampsia in women at high-risk for this condition.
Adult↗
Lysozyme refolding with cyclodextrins: structure-activity relationship.
Cyclodextrins (CDs), in the presence or absence of detergents, have been reported to suppress aggregate formation during the refolding of a number of proteins. A structure-activity relationship study between CD chemistry and refolding of lysozyme was performed and compared to carbonic anhydrase, in order to better understand the mechanism of CD-assisted protein refolding and to identify CDs that could function as good protein folding agents. Among the natural CDs, which have only hydroxyl groups, alpha-CD, with a smaller cavity size was more effective than the oligosaccharide with a larger cavity, gamma-CD. Replacement of the hydroxyls with other functional groups did not improve, but could seriously interfere, with the lysozyme refolding ability of alpha-CD. In case of gamma-CD, substitution of its hydroxyls with other groups either enhanced or diminished its refolding capability towards lysozyme. In general, neutral CDs were better refolding agents than the charged sugars. The presence of anionic substituents like carboxyl and phosphate groups actually promoted aggregate formation and completely abolished the sugar's refolding ability. This effect was more pronounced with lysozyme than with carbonic anhydrase. CDs with cationic functional groups did not show any significant effects on lysozyme refolding. The presence of both anionic and cationic substituents on the same CD molecule was found to partially restore its renaturation ability. Electrophoresis data indicate that CDs, which promoted lysozyme refolding, arrested aggregation at the stage of smaller soluble aggregates. Interestingly, the structure-activity relationship observed with lysozyme was quite similar to that reported for a non-disulfide protein, carbonic anhydrase. These results suggest that the effects of CDs on protein refolding are attributed to their ability to suppress aggregation of proteins. CDs may show properties similar to chaotropic agents, which may help explain their anti-aggregation and protein refolding ability. Besides alpha-CD, a number of other neutral CDs were found to be effective protein folding aids.
2-Hydroxypropyl-beta-cyclodextrin↗
Tristetraprolin regulates Cyclin D1 and c-Myc mRNA stability in response to rapamycin in an Akt-dependent manner via p38 MAPK signaling.
The differential expression of the critical cell cycle control proteins cyclin D1 and c-myc has been shown to result in Akt-dependent hypersensitivity of tumor cells to mTOR inhibitors. We have previously demonstrated that the differential utilization of internal ribosome entry sites within the mRNAs of these transcripts allows maintenance of protein synthesis in the face of rapamycin (rapa) exposure in an Akt-dependent manner. Here, we demonstrate that in addition to this mechanism, cyclin D1 and c-myc mRNA stability is also coordinately regulated following rapa treatment depending on Akt activity status. We identify A/U-rich response elements within the 3' untranslated regions (UTRs) of these transcripts, which confer the observed differential stabilities and show that the RNA-binding protein, tristetraprolin (TTP), interacts with these elements. We also present evidence that TTP accumulates in response to rapa exposure, binds to the cis-acting elements within the cyclin D1 and c-myc 3' UTRs and is differentially serine phosphorylated in an Akt-dependent manner. Furthermore, the differential phosphorylation status of TTP results in its sequestration by 14-3-3 proteins in quiescent Akt-containing cells. Finally, siRNA-mediated knockdown of TTP expression or inhibiting a known regulator of TTP phosphorylation, p38 MAP kinase, abolishes the effects on cyclin D1 and c-myc mRNA stability. We assume that the differential control of cyclin D1 and c-myc mRNA stability and translational efficiency constitutes a coordinate response to rapa contributing to the maintenance of expression of these determinants in rapa-resistant quiescent Akt-containing cells following exposure.
14-3-3 Proteins↗
Confinement-induced instability and adhesive failure between dissimilar thin elastic films.
When two thin soft elastomeric films are separated from each other, an elastic instability develops at the interface. Although similar instability develops for the case of a soft film separating from a rigid adherent, there are important differences in the two cases. For the single-film case, the wavelength of instability is independent of any material properties of the system, and it scales only with thickness of the film. For the two-film case, a co-operative instability mode develops, which is a non-linear function of the thicknesses and the elastic moduli of both films. We investigate the development of such instability by energy minimization procedures. Understanding the nature of this instability is important, as it affects the adhesive compliance of the system and thus the energy release rate in the debonding of soft interfaces.
Adhesives↗
Screening for gynaecological cancers.
BACKGROUND: The role of screening in gynaecological cancers is under evaluation. With mass screening proven effective in significantly reducing cervical cancer mortality, there is an interest in developing other screening methods to detect gynaecological malignancies early. This review covers advances in cervical cancer screening, strategies being investigated in ovarian cancer screening and the lack of justification in screening for endometrial, vulval and vaginal cancers. METHODS: A Medline based literature search was performed for articles relating to screening for different gynaecological malignancies. Additional original papers cited in those identified by the initial search were also reviewed. RESULTS: Advances in cervical cancer screening include liquid-based cytology and HPV testing. Results of ongoing trials are awaited before these can be fully implemented. The results of the two large, multicentre, randomised controlled trials being conducted in the United Kingdom and United States (UKCTOCS and PLCO study, respectively) to assess impact of screening on ovarian cancer mortality will shed some light on the need to implement screening for ovarian cancer in the general population. Novel markers, serum proteomic profiles and Doppler are some of the other technologies being explored. Currently, screening for endometrial cancer is not advocated as most women present with symptoms in early disease with good survival outcomes. Vulval and vaginal cancers are too rare to justify mass screening. CONCLUSION: Methods to screen for various gynaecological malignancies need further evaluation before implementation in the general population. Results of large multicentred trials are awaited. Presently, screening for endometrial, vaginal and vulval cancers is not justified.
Female↗