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排序方式: 共有193条查询结果,搜索用时 22 毫秒
71.
Sobhia ME Paul S Shinde R Potluri M Gundam V Kaur A Haokip T 《Expert opinion on therapeutic patents》2012,22(2):125-153
INTRODUCTION: The protein tyrosine phosphatases (PTPases or PTPs) are highly conserved phosphatases that regulate the tyrosine phosphorylation and consequently, the cellular functions. Protein tyrosine phosphorylation is the major post-translational modification to regulate signal transduction in cells. PTPs control diverse processes such as focal adhesion dynamics, cell-cell adhesion, insulin signaling, cytoskeletal functions, synaptogenesis and neurite growth. The availability of numerous X-ray crystal structures of PTPs, along with their inhibitors, has provided the opportunity for the structure-based design of effective inhibitors having potential for the treatment of various disorders. AREAS COVERED: The main focus of the present review is to get an insight into the most clinically relevant therapeutic PTP inhibitors published in patents over the past 10 years. EXPERT OPINION: Several computational studies are being carried out to understand ligand binding modes, selectivity interactions and conformational changes during inhibitor binding. PTP inhibitors that are of current interest include quinolyl, cyclic alabenzimidazole, pyrazine, (ethynediyl)bis-benzene, pyridopyrimidine, triazolopyridine, cyclo propylphenyl phenyloxamides, oxindole and azoloarin derivatives. The development of allosteric site-directed PTP inhibitors may help in understanding the absorption and selectivity of PTP inhibitors. 相似文献
72.
Masilamani M Commins S Shreffler W 《Immunology and Allergy Clinics of North America》2012,32(1):11-33
Food allergy is an emerging epidemic in the United States and the Western world. The determination of factors that make certain foods allergenic is still not clearly understood. Only a tiny fraction of thousands of proteins and other molecules is responsible for inducing food allergy. In this review, the authors present 3 examples of food allergies with disparate clinical presentations: peanut, soy, and mammalian meat. The potential relationships between allergen structure and function, emphasizing the importance of cross-reactive determinants, immunoglobulin E antibodies to the oligosaccharides, and the immune responses induced in humans are discussed. 相似文献
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Alsalhi M Masilamani V Trinka V Elangovan M Kochupillai V Shah N 《Technology in cancer research & treatment》2011,10(2):145-152
This paper pertains to a new technique based on fluorescence emission spectra (FES), and stokes shift spectra (SSS) of blood plasma, acetone extract of cellular fraction, and urine. These samples were collected from 60 cancer patients of different etiology and 60 age adjusted controls for a single blind study. A set of ratio parameters were obtained from the above spectra (FES and SSS of above three sets of samples), based on the relative intensity of biofluorophores like tryptophan, tyrosine, flavin etc. It was found that these biofluorophores go out of proportion for malignancy of any etiolology. The study was done in two phases: calibration and validation. Based on a certain set of ratios obtained by simple statistical analysis, in the calibration phase, the blinded samples of validation phase were spectrally analysed and classified as normal or malignant. The scoring done by independent oncologists (who were not involved in any part of this new technique) yielded an overall sensitivity of 87%, and specificity of 83%. The result indicate that new optical spectroscopic techniques could be a simple, non-invasive protocol for detection of cancers, particularly in symptomatic cases; or for monitoring the post treated cases of cancer. 相似文献
76.
Marik R Allu M Anchoori R Stearns V Umbricht CB Khan S 《Cancer biology & therapy》2011,11(10):883-892
The estrogen receptor (ER) is a major target for the treatment of breast cancer cells. Genistein, a soy isoflavone, possesses a structure similar to estrogen and can both mimic and antagonize estrogen effects although at high concentrations it inhibits breast cancer cell proliferation. Hence, to enhance the anti-cancer activity of Genistein at lower concentrations, we have synthesized seven structurally modified derivatives of Genistein (MA-6, MA-8, MA-11, MA-19, MA-20, MA-21 and MA-22) based on the structural requirements for an optimal anti-cancer effect. Among those seven, three derivatives (MA-6, MA-8 and MA-19) showed high antiproliferative activity with IC(50) levels in the range of 1-2.5 μM, i.e., at much lower concentrations range than Genistein itself, in three ER-positive breast cancer cell lines (MCF-7, 21PT and T47D) studied. In our analysis, we noticed that at IC(50) concentrations, the MA-6, MA-8 and MA-19 Genistein derivatives induced apoptosis, inhibited ER-α messenger RNA expression and increased the ratio of ER-β to ER-α levels in a manner comparable to the parent compound Genistein. Of note, these three modified Genistein derivatives exerted their effects at concentrations 10-15 times lower than the parent compound, decreasing the likelihood of significant ER- α pathway activation, which has been a concern for Genistein. Hence these compounds might play a useful role in breast cancer chemoprevention. 相似文献
77.
Characteristics and practice profiles of migrant dentist groups in Australia: implications for dental workforce policy and planning
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Madhan Balasubramanian A John Spencer Stephanie D Short Keith Watkins Sergio Chrisopoulos David S Brennan 《International dental journal》2015,65(3):146-155
Introduction: Migrants comprise a growing proportion of the dental workforce in Australia. To date, research on migrant dentists is limited, raising policy questions regarding the motivations for migration, demographic profiles and work patterns. The purpose of this paper was to present findings from the first national survey of migrant dentists in Australia. Methods: All dentists with a primary dental qualification from an overseas institution and registered with the Australian Dental Association (n = 1,872) or enrolled as a graduate student in any of the nine dental schools in Australia (n = 105) were surveyed between January and May 2013. Results: A total of 1,022 participants (response rate = 54.5%) were classifiable into three migrant dentist groups: direct recognition (n = 491); Australian Dental Council (ADC) (n = 411); and alternative pathway (n = 120). Overall, 41.8% of migrant dentists were female. More than half of the ADC group (54.1%) were from lower middle income countries. The most frequent motivation for migration according to the direct recognition group (21.1%) was ‘adventure’, whereas other groups migrated for ‘better opportunity’. The majority of ADC respondents (65%) were under 45 years of age, and a larger proportion worked in the most disadvantaged areas (12.4%), compared with other groups. Gender, marital status, years since arrival in Australia and having children varied between the groups (chi square; P < 0.05). Conclusion: Dentist groups migrate to Australia for different reasons. The large proportion of the migrant dentist workforce sourced from lower middle income countries points towards deficiencies in oral health systems both for these countries and for Australia. The feminisation of the migrant dentist profile could in future affect dentist-practice activity patterns in Australia. Further research, especially on the settlement experiences of these dentists, can provide better insights into issues faced by these dentists, the nature of support that migrant dentists receive in Australia, the probable future patterns of work and potential impact on the dental workforce and dental service provision.Key words: Dental workforce, migrants, national survey, policy, practice profiles 相似文献
78.
David S. Brennan Madhan Balasubramanian A. John Spencer 《International dental journal》2016,66(6):344-349
Objectives: Growth in rates of preventive services has been linked to trends in retention of teeth and the emergence of minimal intervention approaches. In this study, we examined associations between patient-level characteristics and rates of the preventive services dental/prophylaxis and application of remineralisation agents. Methods: A random sample of dentists in Australia was posted a self-administered questionnaire in 2009–2010. A service log was used to collect data on preventive services and patient characteristics. Results: Responses were obtained from 1,148 dentists (response rate = 67%). Preventive service rate models, adjusted according to the age and gender of patients, indicated that insured patients had higher rates of prophylaxis [rate ratio (RR) = 1.39; 95% confidence interval (95% CI): 1.21–1.59) and remineralisation services (RR = 1.85; 95% CI: 1.46–2.33), and that emergency visits had lower rates for prophylaxis (RR = 0.26; 95% CI: 0.20–0.35) and remineralisation services (RR = 0.23; 95% CI: 0.14–0.38). Those who had 20 teeth or more demonstrated higher rates of prophylaxis (RR = 1.41; 95% CI: 1.13–1.75) and remineralisation services (RR = 1.45; 95% CI: 1.02–2.08). Those with decayed teeth had lower rates of prophylaxis (RR = 0.54; 95% CI: 0.46–0.63) and remineralisation services (RR = 0.66; 95% CI: 0.53–0.82). Conclusions: Preventive services were associated with patient age, characteristics of visits and oral health. Patients who were worse off, in terms of attending an emergency visit for the relief of pain and having decayed teeth, had lower rates of preventive care. The findings indicate that patients most in need are missing out on the benefits of preventive dental services.Key words: Dental services, preventive services, dental prophylaxis, remineralisation services, private general practice 相似文献
79.
Burgess SJ Maasho K Masilamani M Narayanan S Borrego F Coligan JE 《Immunologic research》2008,40(1):18-34
NK cells are critical components of our immune system functioning, in part, to recognize and then eradicate virally infected
or tumorigenic cells without previous sensitization. One of the best-characterized activating receptors expressed on NK cells
is the NKG2D receptor, which is capable of transmitting co-stimulatory signals by subsets of T cells. Viruses and tumors have
evolved strategies to evade NKG2D-mediated immune recognition thus highlighting the importance of this receptor in immunity.
This review will focus on the structure of NKG2D and its interaction with its diverse array of ligands, as well as highlighting
current knowledge regarding NKG2D signal transduction and biological mechanisms that govern its cell surface expression. The
impact that NKG2D has in disease pathologies is also assessed. 相似文献
80.
Gorey KM Luginaah IN Schwartz KL Fung KY Balagurusamy M Bartfay E Wright FC Anucha U Parsons RR 《Breast cancer research and treatment》2009,113(3):595-600
Purpose This study examined whether race/ethnicity had differential effects on breast cancer care and survival across age strata
and cohorts within stages of disease. Methods The Detroit Cancer Registry provided 25,997 breast cancer cases. African American and non-Hispanic white, older Medicare-eligible
and younger non-eligible women were compared. Successive historical cohorts (1975–1980 and 1990–1995) were, respectively,
followed until 1986 and 2001. Results African American disadvantages on survival and treatments increased significantly, particularly among younger women who were
much more likely to be uninsured. Within node positive disease all treatment disadvantages among younger African American
women disappeared with socioeconomic adjustment. Conclusions Growth of this racial divide implicates social, rather than biological, forces. Its elimination will require high quality
health care for all.
Madhan Balagurusamy—Masters candidate in statistics at the time that this research was accomplished. 相似文献