Displaying publications 161 - 180 of 23935 in total

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  1. Dehghan F, Muniandy S, Yusof A, Salleh N
    Int J Mol Sci, 2014;15(3):4619-34.
    PMID: 24642882 DOI: 10.3390/ijms15034619
    Ovarian steroids such as estrogen and progesterone have been reported to influence knee laxity. The effect of testosterone, however, remains unknown. This study investigated the effect of testosterone on the knee range of motion (ROM) and the molecular mechanisms that might involve changes in the expression of relaxin receptor isoforms, Rxfp1 and Rxfp2 in the patella tendon and lateral collateral ligament of the female rat knee. Ovariectomized adult female Wistar rats received three days treatment with peanut oil (control), testosterone (125 and 250 μg/kg) and testosterone (125 and 250 μg/kg) plus flutamide, an androgen receptor blocker or finasteride, a 5α-reductase inhibitor. Duplicate groups received similar treatment however in the presence of relaxin (25 ng/kg). A day after the last drug injection, knee passive ROM was measured by using a digital miniature goniometer. Both tendon and ligament were harvested and then analysed for protein and mRNA expression for Rxfp1 and Rxfp2 respectively. Knee passive ROM, Rxfp1 and Rxfp2 expression were significantly reduced following treatment with testosterone. Flutamide or finasteride administration antagonized the testosterone effect. Concomitant administration of testosterone and relaxin did not result in a significant change in knee ROM as compared to testosterone only treatment; however this was significantly increased following flutamide or finasteride addition. Testosterone effect on knee passive ROM is likely mediated via dihydro-testosterone (DHT), and involves downregulation of Rxfp1 and Rxfp2 expression, which may provide the mechanism underlying testosterone-induced decrease in female knee laxity.
    Matched MeSH terms: Female
  2. Tan J
    Nephrology (Carlton), 2014 May;19(5):288-95.
    PMID: 24641721 DOI: 10.1111/nep.12228
    Brunei Darussalam is a small South East Asian country with a high prevalence and incidence of end stage kidney disease (ESRD). This study aims to compare key performance indicators recorded in the Brunei Dialysis and Transplant Registry and department records against international practice. Registries from the USA (USRDS), UK (UK Renal Registry), Australasia (ANZDATA), Europe (ERA-EDTA Registry) and Malaysia (MDTR) were used for comparisons.
    Matched MeSH terms: Female
  3. Goh BS, Ismail MI, Husain S
    J Laryngol Otol, 2014 Mar;128(3):242-8.
    PMID: 24618303 DOI: 10.1017/S002221511400036X
    This study investigated improvements in quality of life associated with eight weeks of montelukast and/or intranasal steroid treatment for moderate to severe allergic rhinitis.
    Matched MeSH terms: Female
  4. Hajrezaie M, Hassandarvish P, Moghadamtousi SZ, Gwaram NS, Golbabapour S, Najihussien A, et al.
    PLoS One, 2014;9(3):e91246.
    PMID: 24618844 DOI: 10.1371/journal.pone.0091246
    Based on the potential of Schiff base compounds to act as sources for the development of cancer chemotherapeutic agents, this in vivo study was performed to investigate the inhibitory properties of the synthetic Schiff base compound Cu(BrHAP)2 on colonic aberrant crypt foci (ACF).
    Matched MeSH terms: Female
  5. Lim CC, Teo BW, Ong PG, Cheung CY, Lim SC, Chow KY, et al.
    Eur J Prev Cardiol, 2015 Aug;22(8):1018-26.
    PMID: 24857889 DOI: 10.1177/2047487314536873
    BACKGROUND: Few studies have examined the impact of chronic kidney disease (CKD) on adverse cardiovascular outcomes and deaths in Asian populations. We evaluated the associations of CKD with cardiovascular disease (CVD) and all-cause mortality in a multi-ethnic Asian population.
    DESIGN: Prospective cohort study of 7098 individuals who participated in two independent population-based studies involving Malay adults (n = 3148) and a multi-ethnic cohort of Chinese, Malay and Indian adults (n = 3950).
    METHODS: CKD was assessed from CKD-EPI estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Incident CVD (myocardial infarction, stroke and CVD mortality) and all-cause mortality were identified by linkage with national disease/death registries.
    RESULTS: Over a median follow-up of 4.3 years, 4.6% developed CVD and 6.1% died. Risks of both CVD and all-cause mortality increased with decreasing eGFR and increasing albuminuria (all p-trend <0.05). Adjusted hazard ratios (HR (95% confidence interval)) of CVD and all-cause mortality were: 1.54 (1.05-2.27) and 2.21 (1.67-2.92) comparing eGFR <45 vs ≥60; 2.81 (1.49-5.29) and 2.34 (1.28-4.28) comparing UACR ≥300 vs <30. The association between eGFR <60 and all-cause mortality was stronger among those with diabetes (p-interaction = 0.02). PAR of incident CVD was greater among those with UACR ≥300 (12.9%) and that of all-cause mortality greater among those with eGFR <45 (16.5%).
    CONCLUSIONS: In multi-ethnic Asian adults, lower eGFR and higher albuminuria were independently associated with incident CVD and all-cause mortality. These findings extend previously reported similar associations in Western populations to Asians and emphasize the need for early detection of CKD and intervention to prevent adverse outcomes.
    Matched MeSH terms: Female
  6. Hooshmand S, Ghaderi A, Yusoff K, Thilakavathy K, Rosli R, Mojtahedi Z
    Asian Pac J Cancer Prev, 2014;15(7):3311-7.
    PMID: 24815488
    BACKGROUND: The consequence of Rho GDP dissociation inhibitor alpha (RhoGDIα) activity on migration and invasion of estrogen receptor positive (ER+) and negative (ER-) breast cancer cells has not been studied using the proteomic approach. Changes in expression of RhoGDIα and other proteins interacting directly or indirectly with RhoGDIα in MCF7 and MDA-MB-231, with different metastatic potentials is of particular interest.

    MATERIALS AND METHODS: ER+ MCF7 and ER- MDA-MB-231 cell lines were subjected to two-dimensional electrophoresis (2-DE) and spots of interest were identified by matrix-assisted laser desorption/ionization time of- flight/time- of-flight (MALDI-TOF/TOF) mass spectrometry (MS) analysis after downregulation of RhoGDIα using short interfering RNA (siRNA) and upregulated using GFP-tagged ORF clone of RhoGDIα.

    RESULTS: The results showed a total of 35 proteins that were either up- or down-regulated in these cells. Here we identifed 9 and 15 proteins differentially expressed with silencing of RhoGDIα in MCF-7 and the MDA-MB-231 cells, respectively. In addition, 10 proteins were differentially expressed in the upregulation of RhoGDIα in MCF7, while only one protein was identified in the upregulation of RhoGDIα in MDA-MB-231. Based on the biological functions of these proteins, the results revealed that proteins involved in cell migration are more strongly altered with RhoGDI-α activity. Although several of these proteins have been previously indicated in tumorigenesis and invasiveness of breast cancer cells, some ohave not been previously reported to be involved in breast cancer migration. Hence, these proteins may serve as useful candidate biomarkers for tumorigenesis and invasiveness of breast cancer cells.

    CONCLUSIONS: Future studies are needed to determine the mechanisms by which these proteins regulate cell migration. The combination of RhoGDIα with other potential biomarkers may be a more promising approach in the inhibition of breast cancer cell migration.

    Matched MeSH terms: Female
  7. Nami Y, Abdullah N, Haghshenas B, Radiah D, Rosli R, Khosroushahi AY
    Anaerobe, 2014 Aug;28:29-36.
    PMID: 24818631 DOI: 10.1016/j.anaerobe.2014.04.012
    Lactobacillus acidophilus is categorized as a probiotic strain because of its beneficial effects in human health and prevention of disease transmission. This study is aimed to characterize the probiotic potential of L. acidophilus 36YL originally isolated from the vagina of healthy and fertile Iranian women. The L. acidophilus 36YL strain was identified using 16S rDNA gene sequencing and characterized by biochemical methodologies, such as antibiotics susceptibility, antimicrobial activity, and acid and bile resistance. The bioactivity of the secretion of this strain on four human cancer cell lines (AGS, HeLa, MCF-7, and HT-29) and one normal cell line (HUVEC) was evaluated by cytotoxicity assay and apoptosis analysis. This newly isolated strain was found to exhibit notable probiotic properties, such as admirable antibiotic susceptibility, good antimicrobial activity, and favorable resistance to acid and bile salt. The results of bioactivity assessment demonstrated acceptable anticancer effects on the four tested cancer cell lines and negligible side effects on the assayed normal cell line. Our findings revealed that the anticancer effect of L. acidophilus 36YL strain secretions depends on the induction of apoptosis in cancer cells. L. acidophilus 36YL strain is considered as a nutraceutical alternative or a topical medication with a potential therapeutic index because of the absence of cytotoxicity to normal cells, but effective toxicity to cancer cell lines.
    Matched MeSH terms: Female
  8. Cheah PL, Looi LM, Teoh KH, Rahman NA, Wong LX, Tan SY
    Asian Pac J Cancer Prev, 2014;15(7):3287-91.
    PMID: 24815484
    BACKGROUND: The interesting preponderance of Chinese with colorectal carcinoma (CRC) amongst the three major ethnic groups in Malaysia prompted a study to determine DNA mismatch repair (MMR) status in our CRC and attempt correlation with patient age, gender and ethnicity as well as location, grade, histological type and stage of tumour. Histologically re-confirmed CRC, diagnosed between 1st January 2005 and 31st December 2007 at the Department of Pathology, University of Malaya Medical Centre, were immunohistochemically stained with monoclonal antibodies to MMR proteins, MLH1, MSH2, MSH6 and PMS2 on the Ventana Benchmark XT autostainer. Of the 142 CRC cases entered into the study, there were 82 males and 60 females (M:F=1.4:1). Ethnically, 81 (57.0%) were Chinese, 32 (22.5%) Malays and 29 (20.4%) Indians. The patient ages ranged between 15-87 years (mean=62.4 years) with 21 cases <50-years and 121 ≥50-years of age. 14 (9.9%) CRC showed deficient MMR (dMMR). Concurrent loss of MLH1 and PMS2 occurred in 10, MSH2 and MSH6 in 2 with isolated loss of MSH6 in 1 and PMS2 in 1. dMMR was noted less frequently amongst the Chinese (6.2%) in comparison with their combined Malay and Indian counterparts (14.8%), and was associated with right sided and poorly differentiated tumours (p<0.05). 3 of the 5 (60.0%) dMMR CRC cases amongst the Chinese and 1 of 9 cases (11.1%) amongst the combined Malay and Indian group were <50-years of age. No significant association of dMMR was noted with patient age and gender, tumour stage or mucinous type.
    Matched MeSH terms: Female
  9. Cheong KC, Ghazali SM, Hock LK, Yusoff AF, Selvarajah S, Haniff J, et al.
    Obes Res Clin Pract, 2014 Mar-Apr;8(2):e154-62.
    PMID: 24743011 DOI: 10.1016/j.orcp.2013.03.004
    INTRODUCTION: Previous studies have proposed the lower waist circumference (WC) cutoffs be used for defining abdominal obesity in Asian populations.
    OBJECTIVE: To determine the optimal cut-offs of waist circumference (WC) in predicting cardiovascular (CV) risk factors in the multi-ethnic Malaysian population.
    METHODS: We analysed data from 32,703 respondents (14,980 men and 17,723 women) aged 18 years and above who participated in the Third National Health and Morbidity Survey in 2006. Gender-specific logistic regression analyses were used to examine associations between WC and three CV risk factors (diabetes mellitus, hypertension, and hypercholesterolemia). The Receiver Operating Characteristic (ROC) curves were used to determine the cut-off values of WC with optimum sensitivity and specificity for detecting these CV risk factors.
    RESULTS: The odds ratio for having diabetes mellitus, hypertension, and hypercholesterolemia, or at least one of these risks, increased significantly as the WC cut-off point increased. Optimal WC cut-off values for predicting the presence of diabetes mellitus, hypertension, hypercholesterolemia and at least one of the three CV risk factors varied from 81.4 to 85.5 cm for men and 79.8 to 80.7 cm for women.
    CONCLUSIONS: Our findings indicate that WC cut-offs of 81 cm for men and 80 cm for women are appropriate for defining abdominal obesity and for recommendation to undergo cardiovascular risk screening and weight management in the Malaysian adult population.
    Study name: National Health and Morbidity Survey (NHMS-2006)
    Matched MeSH terms: Female
  10. Ching SM, Pang YK, Price D, Cheong AT, Lee PY, Irmi I, et al.
    Respirology, 2014 Jul;19(5):689-93.
    PMID: 24708063 DOI: 10.1111/resp.12291
    BACKGROUND AND OBJECTIVE: Early diagnosis of chronic obstructive pulmonary disease (COPD) in primary care settings is difficult to achieve chiefly due to lack of availability of spirometry. This study estimated the prevalence of airflow limitation among chronic smokers using a handheld spirometer in this setting.
    METHODS: This is a cross-sectional study performed on consecutive patients who were ≥40 years old with ≥10 pack-years smoking history. Face-to-face interviews were carried out to obtain demographic data and relevant information. Handheld spirometry was performed according to a standard protocol using the COPd-6 device (Model 4000, Vitalograph, Ennis, Ireland) in addition to standard spirometry. Airflow limitation was defined as ratio of forced expiratory volume in 1 s (FEV1 )/forced expiratory volume in 6 s <0.75 (COPd-6) or FEV1 /forced vital capacity <0.7. Multiple logistic regression analyses were used to determine predictors of airflow limitation.
    RESULTS: A total of 416 patients were recruited with mean age of 53 years old. The prevalence of airflow limitation was 10.6% (n = 44) with COPd-6 versus 6% as gauged using standard spirometry. Risk factors for airflow limitation were age >65 years (odds ratio (OR) 3.732 95% confidence interval (CI): 1.100-1.280), a history of 'bad health' (OR 2.524, 95% CI: 1.037-6.142) and low to normal body mass index (OR 2.914, 95% CI: 1.191-7.190).
    CONCLUSIONS: In a primary care setting, handheld spirometry (COPd-6) found a prevalence of airflow limitation of ∼10% in smokers. Patients were older, not overweight and had an ill-defined history of health problems.
    KEYWORDS: Malaysia; chronic obstructive pulmonary disease; prevalence; primary care; smoke
    Study site: Public primary health‐care clinic (Klinik Kesihatan), Sepang District, Selangor, Malaysia
    Matched MeSH terms: Female
  11. Rathakrishnan A, Klekamp B, Wang SM, Komarasamy TV, Natkunam SK, Sathar J, et al.
    PLoS One, 2014;9(3):e92021.
    PMID: 24647042 DOI: 10.1371/journal.pone.0092021
    With its elusive pathogenesis, dengue imposes serious healthcare, economic and social burden on endemic countries. This study describes the clinical and immunological parameters of a dengue cohort in a Malaysian city, the first according to the WHO 2009 dengue classification.
    Matched MeSH terms: Female
  12. Soga T, Kitahashi T, Clarke IJ, Parhar IS
    Endocrinology, 2014 May;155(5):1944-55.
    PMID: 24605826 DOI: 10.1210/en.2013-1786
    Gonadotropin-inhibitory hormone (GnIH) neurons project to GnRH neurons to negatively regulate reproductive function. To fully explore the projections of the GnIH neurons, we created transgenic rats carrying an enhanced green fluorescent protein (EGFP) tagged to the GnIH promoter. With these animals, we show that EGFP-GnIH neurons are localized mainly in the dorsomedial hypothalamic nucleus (DMN) and project to the hypothalamus, telencephalon, and diencephalic thalamus, which parallels and confirms immunocytochemical and gene expression studies. We observed an age-related reduction in c-Fos-positive GnIH cell numbers in female rats. Furthermore, GnIH fiber appositions to GnRH neurons in the preoptic area were lessened in middle-aged females (70 weeks old) compared with their younger counterparts (9-12 weeks old). The fiber density in other brain areas was also reduced in middle-aged female rats. The expression of estrogen and progesterone receptors mRNA in subsets of EGFP-GnIH neurons was shown in laser-dissected single EGFP-GnIH neurons. We then examined estradiol-17β and progesterone regulation of GnIH neurons, using c-Fos presence as a marker. Estradiol-17β treatment reduced c-Fos labeling in EGFP-GnIH neurons in the DMN of young ovariectomized adult females but had no effect in middle-aged females. Progesterone had no effect on the number of GnIH cells positive for c-Fos. We conclude that there is an age-related decline in GnIH neuron number and GnIH inputs to GnRH neurons. We also conclude that the response of GnIH neurons to estrogen diminishes with reproductive aging.
    Matched MeSH terms: Female
  13. Abu Hassan H, Abd Aziz N, Hassan Y, Hassan F
    PMID: 24868154 DOI: 10.2147/COPD.S56637
    BACKGROUND: Lack of awareness among ex-smokers on the benefits of sustaining smoking cessation may be the main cause of their smoking relapse. This study explored health-related quality of life (HRQoL) and hospital admission amongst chronic obstructive pulmonary disease (COPD) patients according to the duration of smoking cessation.
    MATERIALS AND METHODS: This study recruited COPD patients from a chest clinic who agreed to participate in a medication therapy-adherence program from January to June 2013. They were interviewed during their visits to obtain information regarding their smoking history and HRQoL. They were divided into three groups according to smoking status (sustained quitters, quit ≥5 years; quitters, quit <5 years; and smokers, smoking at least one cigarette/day). The effects of the duration of cessation on HRQoL and hospital admission were analyzed using a multinomial logistic model.
    RESULTS: A total of 117 participants with moderate COPD met the inclusion criteria, who were comprised of 41 sustained quitters, 40 quitters, and 36 smokers. Several features were similar across the groups. Most of them were married elderly men (aged >64 years) with low-to-middle level of education, who smoked more than 33 cigarettes per day and had high levels of adherence to the medication regimen. The results showed that sustained quitters were less likely to have respiratory symptoms (cough, phlegm and dyspnea) than smokers (odds ratio 0.02, confidence interval 0-0.12; P<0.001). The hospital admission rate per year was increased in quitters compared to smokers (odds ratio 4.5, confidence interval 1.91-10.59; P<0.005).
    CONCLUSION: A longer duration of quitting smoking will increase the benefits to COPD patients, even if they experience increased episodic respiratory symptoms in the early period of the cessation. Thus, the findings of this study show the benefits of early smoking cessation.
    KEYWORDS: HRQoL; chronic obstructive pulmonary disease (COPD); hospital admission and hospital stay
    Study site: Chest Clinic, Hospital Melaka, Malaysia
    Matched MeSH terms: Female
  14. Arbabi L, Baharuldin MT, Moklas MA, Fakurazi S, Muhammad SI
    Behav Brain Res, 2014 Sep 1;271:65-71.
    PMID: 24867329 DOI: 10.1016/j.bbr.2014.05.036
    Postpartum depression (PPD) is a psychiatric disorder that occurs in 10-15% of childbearing women. It is hypothesized that omega-3 fatty acids, which are components of fish oil, may attenuate depression symptoms. In order to examine this hypothesis, the animal model of postpartum depression was established in the present study. Ovariectomized female rats underwent hormone-simulated pregnancy (HSP) regimen and received progesterone and estradiol benzoate or vehicle for 23 days, mimicking the actual rat's pregnancy. The days after hormone termination were considered as the postpartum period. Forced feeding of menhaden fish oil, as a source of omega-3, with three doses of 1, 3, and 9g/kg/d, fluoxetine 15mg/kg/d, and distilled water 2ml/d per rat started in five postpartum-induced and one vehicle group on postpartum day 1 and continued for 15 consecutive days. On postpartum day 15, all groups were tested in the forced swimming test (FST) and open field test (OFT), followed by a biochemical assay. Results showed that the postpartum-induced rats not treated with menhaden fish oil, exhibited an increase in immobility time seen in FST, hippocampal concentration of corticosterone and plasmatic level of corticosterone, and pro-inflammatory cytokines. These depression-related effects were attenuated by supplementation of menhaden fish oil with doses of 3 and 9g/kg. Moreover, results of rats supplemented with menhaden fish oil were comparable to rats treated with the clinically effective antidepressant, fluoxetine. Taken together, these results suggest that menhaden fish oil, rich in omega-3, exerts beneficial effect on postpartum depression and decreases the biomarkers related to depression such as corticosterone and pro-inflammatory cytokines.
    Matched MeSH terms: Female
  15. Gan GG, Subramaniam R, Bee PC, Chin EF, Abdul-Halim H, Tai MC
    Asian Pac J Cancer Prev, 2014;15(4):1703-6.
    PMID: 24641394
    BACKGROUND: The current standard treatment for patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) is rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). A significant number of patients were not treated with recommended dose of rituximab due to limited financial resources in Malaysia. This study evaluates the efficacy of R-CHOP like chemotherapy in Malaysian patients with DLBCL.

    MATERIALS AND METHODS: The study comprised a retrospective analysis of patients with DLBCL treated at a single centre. The outcome was compared with patients who were treated with R-CHOP like and CHOP like chemotherapy. Patients who were treated with lower dose of rituximab was subanalysed for outcome.

    RESULTS: A total of 86 patients who had CHOP-like chemotherapy were included. Only 39 (45%) patients had rituximab and only 12 (29%) patients had the recommended dose. The overall response (OR) and complete response (CR) rates were 88% and 81% respectively. There was no significant difference in OR and CR in patients who had rituximab and those without rituxmab. Those with International Prognostic Index (IPI) score of ≤ 2 had significant higher CR rate, progression free survival (PFS) and overall survival (p<0.001).

    CONCLUSIONS: The lack of significant improvement in CR and DFS in our patients may be due to an inadequate dose of rituximab.

    Matched MeSH terms: Female
  16. Chow PK, Poon DY, Khin MW, Singh H, Han HS, Goh AS, et al.
    PLoS One, 2014;9(3):e90909.
    PMID: 24614178 DOI: 10.1371/journal.pone.0090909
    The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies.
    Matched MeSH terms: Female
  17. Hamzi Abdul Raub S, Isa NM, Zailani HA, Omar B, Abdullah MF, Mohd Amin WA, et al.
    Asian Pac J Cancer Prev, 2014;15(2):651-6.
    PMID: 24568473
    BACKGROUND: Cervical cancer is the third commonest type of cancer among women in Malaysia. Our aim was to determine the distribution of human papilloma virus (HPV) genotypes in cervical cancer in our multi-ethnic population.

    MATERIALS AND METHODS: This was a multicentre study with a total of 280 cases of cervical cancer from 4 referral centres in Malaysia, studied using real-time polymerase chain reaction (qPCR) detection of 12 high risk-HPV genotypes.

    RESULTS: Overall HPV was detected in 92.5% of cases, in 95.9% of squamous cell carcinomas and 84.3%of adenocarcinomas. The five most prevalent high-risk HPV genotypes were HPV 16 (68.2%), 18 (40%), 58 (10.7%), 33 (10.4%) and 52 (10.4%). Multiple HPV infections were more prevalent (55.7%) than single HPV infections (36.8%). The percentage of HPV positive cases in Chinese, Malays and Indians were 95.5%, 91.9% and 80.0%, respectively. HPV 16 and 18 genotypes were the commonest in all ethnic groups. We found that the percentage of HPV 16 infection was significantly higher in Chinese (75.9%) compared to Malays (63.7%) and Indians (52.0%) (p<0.05), while HPV 18 was significantly higher in Malays (52.6%) compared to Chinese (25.0%) and Indians (28%) (p<0.05). Meanwhile, HPV 33 (17.9%) and 52 (15.2%) were also more commonly detected in the Chinese (p<0.05).

    CONCLUSIONS: This study showed that the distribution of HPV genotype in Malaysia is similar to other Asian countries. Importantly, we found that different ethnic groups in Malaysia have different HPV genotype infection rates, which is a point to consider during the implementation of HPV vaccination.

    Matched MeSH terms: Female
  18. Cartwright-Terry M, Yates J, Tan CK, Pengas IP, Banks JV, McNicholas MJ
    Arthroscopy, 2014 Jul;30(7):811-7.
    PMID: 24794571 DOI: 10.1016/j.arthro.2014.02.039
    To present a 5-year comparison of the functional outcomes of combined anterior cruciate ligament (ACL) and posterolateral corner (PLC) reconstruction with those of isolated ACL reconstruction.
    Matched MeSH terms: Female
  19. Daud NM, Ismail NA, Thomas EL, Fitzpatrick JA, Bell JD, Swann JR, et al.
    Obesity (Silver Spring), 2014 Jun;22(6):1430-8.
    PMID: 24715424 DOI: 10.1002/oby.20754
    OBJECTIVE: To investigate the effect of nutrient stimulation of gut hormones by oligofructose supplementation on appetite, energy intake (EI), body weight (BW) and adiposity in overweight and obese volunteers.

    METHODS: In a parallel, single-blind and placebo-controlled study, 22 healthy overweight and obese volunteers were randomly allocated to receive 30 g day(-1) oligofructose or cellulose for 6 weeks following a 2-week run-in. Subjective appetite and side effect scores, breath hydrogen, serum short chain fatty acids (SCFAs), plasma gut hormones, glucose and insulin concentrations, EI, BW and adiposity were quantified at baseline and post-supplementation.

    RESULTS: Oligofructose increased breath hydrogen (P 

    Matched MeSH terms: Female
  20. Maiti AK, Kim-Howard X, Motghare P, Pradhan V, Chua KH, Sun C, et al.
    Hum Mol Genet, 2014 Aug 1;23(15):4161-76.
    PMID: 24608226 DOI: 10.1093/hmg/ddu106
    Integrin alpha M (ITGAM; CD11b) is a component of the macrophage-1 antigen complex, which mediates leukocyte adhesion, migration and phagocytosis as part of the immune system. We previously identified a missense polymorphism, rs1143679 (R77H), strongly associated with systemic lupus erythematosus (SLE). However, the molecular mechanisms of this variant are incompletely understood. A meta-analysis of published and novel data on 28 439 individuals with European, African, Hispanic and Asian ancestries reinforces genetic association between rs1143679 and SLE [Pmeta = 3.60 × 10(-90), odds ratio (OR) = 1.76]. Since rs1143679 is in the most active region of chromatin regulation and transcription factor binding in ITGAM, we quantitated ITGAM RNA and surface protein levels in monocytes from patients with each rs1143679 genotype. We observed that transcript levels significantly decreased for the risk allele ('A') relative to the non-risk allele ('G'), in a dose-dependent fashion: ('AA' < 'AG' < 'GG'). CD11b protein levels in patients' monocytes were directly correlated with RNA levels. Strikingly, heterozygous individuals express much lower (average 10- to 15-fold reduction) amounts of the 'A' transcript than 'G' transcript. We found that the non-risk sequence surrounding rs1143679 exhibits transcriptional enhancer activity in vivo and binds to Ku70/80, NFKB1 and EBF1 in vitro, functions that are significantly reduced with the risk allele. Mutant CD11b protein shows significantly reduced binding to fibrinogen and vitronectin, relative to non-risk, both in purified protein and in cellular models. This two-pronged contribution (nucleic acid- and protein-level) of the rs1143679 risk allele to decreasing ITGAM activity provides insight into the molecular mechanisms of its potent association with SLE.
    Matched MeSH terms: Female
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