To

test for other factors influencing the expression of known liver autoantigens in the thymus and their relationship with the observed sex difference in AIH susceptibility, B6.129S2-Airetm1.1Doi/J Ipatasertib clinical trial transgenic Aire knockout mice were studied. Aire, which stands for Autoimmune Regulator, is a transcription factor responsible for the ectopic expression of peripheral antigens in the thymus to allow deletion of self-reactive T cells. FTCD but not CYP2D9 is, as insulin,16 under control of the Aire transcription factor (Fig. 3C). The invalidation of one copy of the Aire gene in heterozygous mice (+/0) lowers the expression of FTCD in the thymus (Fig. 3C). Therefore, heterozygous Aire mice offers a model in which the importance of partial failure in T cell–negative selection for specific liver autoantigens on AIH development can be studied. After xenoimmunization, male and female Aire heterozygous mice showed the same sex-bias as observed in C57BL/6 mice (Figs. 1B, 3D). Therefore, the invalidation of one copy of the Aire gene in heterozygous mice (+/0) did not modulate the grade of liver inflammation compared with wild-type mice (+/+) (Fig. 3D). Peripheral tolerance by regulatory T cells could influence the development of Gefitinib ic50 an autoimmune hepatitis in mice. Xenoimmunized 7-week-old C57BL/6 male mice show a statistically significant higher percentage of Tregs

in the spleen, blood, and liver than vaccinated females of the same age (Fig. 4A). The same difference is observed in vaccinated heterozygous Aire mice. Male mice show higher levels of regulatory T cells in the spleen, blood, and liver when compared with females (Fig. 4B). Significantly higher levels of regulatory T cells are found Ribose-5-phosphate isomerase in liver infiltrates of male mice compared with female where regulatory T cells were virtually absent (Fig. 4B). Testes are an immunological privileged site, and as such, provide an environment able to suppress and control immune responses. In C57BL/6 mice, ectopic expression of

FTCD and CYP2D9 was found in testes (Fig. 5A), and their expression was independent of the Aire transcription factor in this organ (Fig. 5B). This finding suggests that testes could influence susceptibility to AIH through peripheral conversion of autoreactive naïve T cells to FoxP3+ regulatory T cells. Sexual hormones can also directly modulate immune responses locally and systemically, and in doing so, alter the development of an autoimmune disease. Therefore, to assess the role of testes and sexual hormones on AIH susceptibility, we xenoimmunized castrated male C57BL/6 mice, supplemented or not with physiological levels of 17β-estradiol. After an 8-month follow-up, castrated male C57BL/6, supplemented or not with 17β-estradiol, showed a similar grade of liver inflammation after xenoimmunization than vaccinated male C57BL/6 mice (Fig. 6A).

Such lateralized recruitment is the hallmark of a horizontal head-turning synergy

(Corneil et al., 2001), and is seen following stimulation of all oculomotor structures studied to date (Corneil et al., 2002; Elsley et al., 2007; Farshadmanesh et al., 2008; Chapman et al., 2012). Note, however, that the magnitude and exact timing of the recruitment sequence evoked by ICMS of an oculomotor structure does differ from that used volitionally; in particular, the absolute magnitude of agonist recruitment is less for volitional movements, and the recruitment or silencing of a given muscle tends to be more staggered in volitional movements as well (Corneil et al., 2001). Our quantification of the Wnt assay effects of short-duration ICMS-SEF focuses on the activity Deforolimus ic50 of the contralateral muscles, as the strength of inhibition of ipsilateral muscles cannot be quantified and depends on the level of background EMG preceding ICMS-SEF. We emphasize again that ipsilateral muscle inhibition always accompanied contralateral muscle recruitment, consistent with ICMS-SEF recruiting a contralateral

head-turning synergy, rather than causing a generalized arousal that would presumably be related to a bilateral increase in both ipsilateral and contralateral muscle tone. As mentioned in the Methods, we pooled normalized EMG activity across the three contralateral muscles, as similar profiles of recruitment were observed on OCI, RCP maj and SPL; such normalized activity is represented in Figs 4-6. We quantified both the baseline level of neck EMG preceding stimulation (averaged over 10 ms preceding stimulation), and the increase in neck EMG above

baseline (see representation of these measures in the top row of Fig. 4A). Our rationale for doing so is because our previous work (Chapman & Corneil, 2011) detailed modulation of neck muscle activity during the fixation period with the consolidation of the instruction to make a pro- or anti-saccade, and during the post-cue interval depending on the side of the cue. We summarize these patterns briefly here as they influence the interpretation of the neck EMG evoked by ICMS-SEF. On control trials, neck EMG during the fixation interval began to diverge gradually C-X-C chemokine receptor type 7 (CXCR-7) ~300–400 ms after acquisition of the FP (Fig. 4B), eventually becoming ~10% higher prior to cue onset in pro- vs. anti-saccade trials. Such divergence reflects a top-down consolidation of task instruction, and was observed in both monkeys S and Z. This pattern of recruitment was seen in one of two different monkeys in our previous study (Chapman & Corneil, 2011), with the other monkey displaying significantly greater activity before anti-saccades. The gradual decrease in neck EMG activity during the fixation interval also shows that the animals were not co-contracting their neck, as might have been expected if they were bracing for the increasing probability of stimulation as the fixation interval wore on.

Conclusion: This is the first report on genetic diversity of H. pylori based on vacA and cagA genes in Sabah and is valuable to understand the role of genetic diversity of H. pylori strain in disease outcome. Key Word(s): 1. Helicobacter pylori; 2. Genotyping; 3. vacA; 4. cagA; Presenting Author: MASA CAVLINA selleck compound Additional Authors: MILORAD OPACIC, HRVOJE IVEKOVIC, PAVE MARKOS, KATJA GRUBELIC RAVIC,

TOMISLAV BRKIC, NADAN RUSTEMOVIC Corresponding Author: MASA CAVLINA Affiliations: University Hospital Centre Zagreb Objective: Our aim was to establish the prevalence of Helicobacter pylori (H. pylori) infection in patients presented with upper gastrointestinal bleeding and hospitalised at the Reference Centre for interventional gastroenterology of the Ministry of health of Republic of Croatia, Department of gastroenterology and hepatology, University Hospital Centre Zagreb in the period 2007–2011, and to investigate the time trends in that period. Methods: In 566 patients admitted to the hospital with acute upper gastrointestinal Small molecule library bleeding early upper endoscopy was performed to find the source of bleeding and to take biopsy specimens for identification of H. pylori infection and histological examination. Results: The main indications for endoscopy were melena (55.3%, 313/566) and hematemesis (25.3%, 143/566). The overall prevalence of H. pylori infection was 20.4 percent (115/566). In the period 2007–2011

there has been a decline in the prevalence of H. Pylori infection, from 25.2% (31/123) in 2007 to 18.4% (14/76) in 2011. Prevalence of the infection varied among patients with different endoscopic and histological diagnoses. Patients with peptic ulcer disease had the highest prevalence (25.2%, 79/313), compared to other endoscopic findings. According to histological findings in the gastric mucosa, prevalence of the bacteria was highest

in patients who had chronic active gastritis (61%, 89/146). Conclusion: This research confirmed a reported decline in the overall prevalence of H. Pylori infection in patients presented with upper gastrointestinal bleeding. Considering the fact that the prevalence of upper gastrointestinal Alanine-glyoxylate transaminase bleeding remained mostly stable, a decline in prevalence of H. Pylori infection indicates that the major role in the etiology of bleeding in our country might have the abuse of non-steroidal anti-inflammatory drugs. A longer study period, with more patients included may show more definite trends. Key Word(s): 1. Helicobacter pylori; 2. bleeding ulcer; 3. upper GI bleeding; Presenting Author: JOSIP BAGO Additional Authors: ZELJKA BELOSIC HALLE, VINKO BAKULA, ROSANA TROSKOT PERIC, MARINKO MARUSIC, KRESIMIR LUETIC, DRAGAN JURCIC, ANTE BILIC, ANTO DOMINKOVIC Corresponding Author: JOSIP BAGO Affiliations: Clinical Hospital Objective: Since claritromycine resistance rises, efficacy of standard primary treatment for H. pylori infection is lower.

69 Among populations of Asian ethnicity, studies from Japan failed to find a consistent picture of HLA class II associations with PBC,50, 51, 60 with an

association between PBC and DR2 in one,50 DPB1*0501 in another,60 and DRB1*0803 in a third.51 However, although there was a lack of consistent associations between specific DRB1 alleles and PBC in Japan, a recent study suggested that different HLA variants may relate to clinical features of disease. Indeed, Nakamura and colleagues reported a strong association of an HLA-DRB1*0405 and DRB1*0803 with disease only in the subset of patients positive for anti-sp100 (odds ratio = 1.61), a well-known PBC-specific MK-8669 purchase serum anti-nuclear autoantibody, and anticentromere antibodies (odds ratio = 2.30).70 Interestingly, Hirschfield et al. found similar data in Caucasian populations.73

Also, because of the potential clinical implication, future association studies should address the link between different HLA variants and immunological phenotypes in PBC. Overall, we can conclude that the picture of HLA class II involvement in PBC was quite complex mTOR inhibitor and uninteresting until recently. On the basis of the above data, it is clear why until recently HLA variants did not arouse great interest of basic and clinical researchers working to characterize the molecular mechanisms that contribute to disease development, and more specifically, for understanding the role of genetics in PBC. This began to change when our group showed that beyond the consistent (but weak) positive

association with HLA DRB1*08 allele, PBC was also strongly associated with two protective HLA variants, DRB1*11 and DRB1*13 (first reported in abstract form in 200512).13 In particular, by typing for HLA class II polymorphisms in a large cohort of 664 Italian patients with PBC and 1992 controls, we confirmed the known positive association Sitaxentan with DRB1*08 (odds ratio = 3.3), whereas we reported for the first time the protective alleles DRB1*11 (odds ratio = 0.4) and DRB1*13 (odds ratio = 0.7). A weak association with HLA DRB1*02 was also found, and only the associations with DRB1*08 and DRB1*11 were common to all geographical areas of Italy (Northern, Central, and Southern Italy).13 These results were later confirmed in a large UK set of patients and controls in which protection against PBC was associated with DRB1*13 (odds ratio = 0.65) along with a positive association with the class II MHC allele DRB1*0801 (odds ratio = 3.05).14 The finding is of great interest, because the two HLA variants found to be protective for PBC suggest possible disease mechanisms as having a protective role for multiple infectious diseases. Indeed, these studies suggest that the HLA-DRB1*11 allele exerts a strong protective role against hepatitis C virus,74 human papilloma viruses,75 and human immunodeficiency virus.

69 Among populations of Asian ethnicity, studies from Japan failed to find a consistent picture of HLA class II associations with PBC,50, 51, 60 with an

association between PBC and DR2 in one,50 DPB1*0501 in another,60 and DRB1*0803 in a third.51 However, although there was a lack of consistent associations between specific DRB1 alleles and PBC in Japan, a recent study suggested that different HLA variants may relate to clinical features of disease. Indeed, Nakamura and colleagues reported a strong association of an HLA-DRB1*0405 and DRB1*0803 with disease only in the subset of patients positive for anti-sp100 (odds ratio = 1.61), a well-known PBC-specific SAHA HDAC price serum anti-nuclear autoantibody, and anticentromere antibodies (odds ratio = 2.30).70 Interestingly, Hirschfield et al. found similar data in Caucasian populations.73

Also, because of the potential clinical implication, future association studies should address the link between different HLA variants and immunological phenotypes in PBC. Overall, we can conclude that the picture of HLA class II involvement in PBC was quite complex selleck compound and uninteresting until recently. On the basis of the above data, it is clear why until recently HLA variants did not arouse great interest of basic and clinical researchers working to characterize the molecular mechanisms that contribute to disease development, and more specifically, for understanding the role of genetics in PBC. This began to change when our group showed that beyond the consistent (but weak) positive

association with HLA DRB1*08 allele, PBC was also strongly associated with two protective HLA variants, DRB1*11 and DRB1*13 (first reported in abstract form in 200512).13 In particular, by typing for HLA class II polymorphisms in a large cohort of 664 Italian patients with PBC and 1992 controls, we confirmed the known positive association Atezolizumab ic50 with DRB1*08 (odds ratio = 3.3), whereas we reported for the first time the protective alleles DRB1*11 (odds ratio = 0.4) and DRB1*13 (odds ratio = 0.7). A weak association with HLA DRB1*02 was also found, and only the associations with DRB1*08 and DRB1*11 were common to all geographical areas of Italy (Northern, Central, and Southern Italy).13 These results were later confirmed in a large UK set of patients and controls in which protection against PBC was associated with DRB1*13 (odds ratio = 0.65) along with a positive association with the class II MHC allele DRB1*0801 (odds ratio = 3.05).14 The finding is of great interest, because the two HLA variants found to be protective for PBC suggest possible disease mechanisms as having a protective role for multiple infectious diseases. Indeed, these studies suggest that the HLA-DRB1*11 allele exerts a strong protective role against hepatitis C virus,74 human papilloma viruses,75 and human immunodeficiency virus.

69 Among populations of Asian ethnicity, studies from Japan failed to find a consistent picture of HLA class II associations with PBC,50, 51, 60 with an

association between PBC and DR2 in one,50 DPB1*0501 in another,60 and DRB1*0803 in a third.51 However, although there was a lack of consistent associations between specific DRB1 alleles and PBC in Japan, a recent study suggested that different HLA variants may relate to clinical features of disease. Indeed, Nakamura and colleagues reported a strong association of an HLA-DRB1*0405 and DRB1*0803 with disease only in the subset of patients positive for anti-sp100 (odds ratio = 1.61), a well-known PBC-specific RXDX-106 chemical structure serum anti-nuclear autoantibody, and anticentromere antibodies (odds ratio = 2.30).70 Interestingly, Hirschfield et al. found similar data in Caucasian populations.73

Also, because of the potential clinical implication, future association studies should address the link between different HLA variants and immunological phenotypes in PBC. Overall, we can conclude that the picture of HLA class II involvement in PBC was quite complex PF-02341066 chemical structure and uninteresting until recently. On the basis of the above data, it is clear why until recently HLA variants did not arouse great interest of basic and clinical researchers working to characterize the molecular mechanisms that contribute to disease development, and more specifically, for understanding the role of genetics in PBC. This began to change when our group showed that beyond the consistent (but weak) positive

association with HLA DRB1*08 allele, PBC was also strongly associated with two protective HLA variants, DRB1*11 and DRB1*13 (first reported in abstract form in 200512).13 In particular, by typing for HLA class II polymorphisms in a large cohort of 664 Italian patients with PBC and 1992 controls, we confirmed the known positive association Methane monooxygenase with DRB1*08 (odds ratio = 3.3), whereas we reported for the first time the protective alleles DRB1*11 (odds ratio = 0.4) and DRB1*13 (odds ratio = 0.7). A weak association with HLA DRB1*02 was also found, and only the associations with DRB1*08 and DRB1*11 were common to all geographical areas of Italy (Northern, Central, and Southern Italy).13 These results were later confirmed in a large UK set of patients and controls in which protection against PBC was associated with DRB1*13 (odds ratio = 0.65) along with a positive association with the class II MHC allele DRB1*0801 (odds ratio = 3.05).14 The finding is of great interest, because the two HLA variants found to be protective for PBC suggest possible disease mechanisms as having a protective role for multiple infectious diseases. Indeed, these studies suggest that the HLA-DRB1*11 allele exerts a strong protective role against hepatitis C virus,74 human papilloma viruses,75 and human immunodeficiency virus.

In 1991, the lack of reliable EA risk estimates Venetoclax cell line made management of high-grade

dysplasia a medical variant of Russian roulette.1 Then, the only options were to do nothing or have an esophagectomy. Now there are risk estimates, but they still leave clinicians with an uncomfortably high level of uncertainty. A recent systematic review appropriately concluded that there were only four technically acceptable reports66–69 on the EA risk among the 196 publications identified as reporting on high-grade dysplasia.70 These four studies have a combined experience of 1241 patient years in 236 patients. Figure 4 shows that the pooled weighted risk estimate for progression to EA was 65.8 per 1000 patient-years or, put another way, during one year of observation,

a patient with high-grade dysplasia has a 6.6% risk for development of EA. This is a lower risk than most would believe is the case from their clinical experience. Figure 4 reveals the problem with a risk estimate of 65.8 per 1000 patient-years. The range of risk estimates for the four studies is almost five-fold! The Schnell study,68 which found an implausibly low risk of progression of high-grade dysplasia to EA of 22.7 per 1000 patient-years, accounts for 577 patient years, 46% of the pooled duration of observation of Selumetinib manufacturer 4��8C the four studies. The Schnell study also reported the extraordinary and highest-recorded incidence of low-grade dysplasia of 67.2%68 in Vieth’s previously mentioned tabulation of studies.47 This author concludes that the only plausible explanation for the results of Schnell et al. is that what is categorized as high- (and low-) grade dysplasia in their institution differs substantially from other BE research centers. The significant clinical implications of the discordant

data on EA risk are discussed below in the section on management of high-grade dysplasia. A review of reports on cause-specific mortality in BE patients undergoing surveillance found that only 9% of these patients die as a result of EA5. This could be interpreted as a triumph for surveillance, but the reality is that most BE patients die of other causes, most commonly cardiovascular, without development of high-grade dysplasia or EA, because they are, on average, elderly and have a high rate of comorbidities.5 Clinicians need to temper their choice of management options for EA risk in the light of this (Fig. 2). In 1990, it was noted that H2-receptor antagonists failed to heal esophagitis in a high proportion of BE patients and, in the first flush of PPI therapy, there were minimal data on the treatment of BE with these agents.

Conclusions.— The available TGF-beta inhibitor evidence suggests that naproxen sodium is more effective but may cause more adverse events than placebo in the acute treatment of moderate to severe migraine. It is effective in reducing headache intensity, rendering pain-free at 2 hours

and improving migraine-associated symptoms. However, its effectiveness relative to other active comparators needs to be better defined by appropriate head-to-head clinical trials. “
“To evaluate the geographic location of the United Council for Neurologic Subspecialties (UCNS)-certified headache subspecialists as compared with ratios of expected migraine and chronic migraine populations in the United States. The UCNS is a professional medical organization that accredits fellowship programs and certifies physicians who demonstrate find more competence in various neurologic

subspecialties, including headache medicine. There are a limited number of UCNS-certified headache subspecialists currently practicing in the United States. All of the UCNS-certified headache subspecialists were geographically located and compared with demographic data about state populations obtained from the U.S. Census. The expected migraine and chronic migraine populations were calculated for each state based on recently published epidemiologic data. Ratios of UCNS-certified headache subspecialists to expected migraine and chronic migraine populations were compared for each state. These data were then organized by U.S. Census region and division. As

of the 2012 examination cycle, 416 UCNS-certified headache subspecialists are currently practicing in the United States. The states with GBA3 the highest number of headache subspecialists include New York, California, Ohio, Texas, Florida, and Pennsylvania. Six states have zero headache subspecialists, eight states have one headache subspecialist, and five states have two headache subspecialists. As per the U.S. Census, the total U.S. population for ages 12 years and older is 259,908,563. The total expected migraine population (11.79% of the general population) for ages 12 years and older is 30,594,362. The total expected chronic migraine population (0.91% of the general population) for ages 12 years and older is 2,361,397. The states with the best ratios of headache subspecialists to expected migraine and chronic migraine populations include the District of Columbia, New Hampshire, New York, and Nebraska. Besides states with zero headache subspecialists, the states with the worst ratios of headache subspecialists to expected migraine and chronic migraine populations include Oregon, Mississippi, Arkansas, and Kansas. When organized by U.S. Census regions, the Northeast has the best ratios of headache subspecialists to expected migraine and chronic migraine populations, while the West has the worst ratios of headache subspecialists to expected migraine and chronic migraine populations. In terms of U.S.

Understanding the mechanisms in ‘transgenic’ B cell induced tolerance will help us move these studies closer to the bedside. The research summarized herein has been supported during the last decade by grants from the National Institute of Health (RO1 HL061883, RO1 AI035622 and RO1DK068343) and from the Juvenile Diabetes Foundation, National Multiple Sclerosis Foundation and the National Hemophilia Foundation, US. The author is indebted to the following colleagues for their contributions during the last decade: Rajeev Agarwal, Greg Carey,

Indira Carey, Rachel Caspi, Moustapha El-Amine, Donna Farber, Yufei Jiang, Xin Li, Jennifer Hinshaw, Elizabeth Kadavil, Yubin Kang, Zara Karabekian, Tie Chi Lei, Wei Liang, Mary Litzinger, Damaris Lopez, Marco Melo, Kamal Moudgil, Jiahua Qian, Shailesh Satpute, Jonathan Skupsky, Nadia Soukhareva, Yan Su, Tatyana Pozharskaya and learn more Selumetinib mouse Elias Zambidis. The author stated that he had no interests which might be perceived as posing a conflict or bias. “
“Prophylactic use of treatment is important

for good outcomes in haemophilia, yet adherence can be suboptimal. To better understand the relationship between treatment adherence and patients’ beliefs about treatment there is a need to quantify patients’ treatment attitudes. The aim of this study was to develop a brief, clinically relevant, patient-reported outcome (PRO) to measure ease of use and patients’ preference for haemophilia treatment. Mephenoxalone A 40-item questionnaire was completed by male adults with haemophilia A from Austria, Germany, Italy, Spain and the UK. Robust statistical methods for item evaluation including item-level statistics, dimensionality analyses and input from clinical and outcomes experts were used to inform item reduction. Retained items were subjected to psychometric evaluation including exploratory factor analysis (EFA), known-groups validity and internal consistency reliability. 273 patients completed the questionnaire. Of the 40 items, 28 items were flagged for possible deletion based on item-level statistics, three of which were retained due to clinical

relevance. Two items had acceptable statistical performance but were deleted based on low clinical relevance. A total of 13 items were retained. EFA produced a conceptually defined 5-factor solution. The survey had acceptable known-groups validity and internal consistency. Refinements were made to wording and scoring, and one new item was added to assess general ease of use, resulting in a 14-item questionnaire – the HaemoPREF. Preliminary measurement properties of the HaemoPREF support the instrument to evaluate patient perception and preference for haemophilia treatment. Further psychometric evaluation is required to examine and confirm the measurement properties of the scale. “
“The prescribing and dispensing of factor replacement products have come under scrutiny in recent years.

Hepatic lipid accumulation results from an imbalance between lipid availability and lipid disposal.[3] Several metabolic nuclear receptors (NRs) and transcription factors, such as peroxisome proliferator-activated receptors (PPARs), farnesoid X receptor (FXR), pregnane X receptor (PXR), and constitutive androstane receptor (CAR), have been reported to be critical for hepatic lipid homeostasis by controlling circulating lipid uptake, de novo lipogenesis, free fatty acid oxidation, and TG-rich lipoprotein secretion in the liver.[4, 5] Although liver X receptors (LXRs), comprising LXR-α

and LXR-β, mainly act as intracellular cholesterol sensors whose activation leads to protection from cholesterol overload,[6] their role in the regulation of fatty acid and TG metabolism is becoming clearer.[7] LXR isoform nonselective agonist TO901317 induces fatty liver and promotes the secretion of large, TG-rich 3-MA concentration very-low-density Bafilomycin A1 solubility dmso lipoprotein particles in mice,[8] largely through the induction of lipogenic genes, including sterol

regulatory element-binding protein 1c (SREBP-1c), carbohydrate-responsive element-binding protein, stearoyl-CoA (coenzyme A) desaturase 1, and fatty acid synthase (FAS).[9] It has recently been reported that LXR activation may also regulate gene expression of thyroid hormone-responsive SPOT RANTES 14 homolog (Thrsp),[10] a gene abundantly present in lipogenic tissues, where it is rapidly up-regulated by lipogenic stimuli, including thyroid hormone and a high-carbohydrate diet.[11] Previous studies demonstrate that Thrsp expression is directly under transcriptional regulation by the NRs, thyroid hormone receptor (TR) and CAR,[12, 13] and it may play an important role in lipogenic processes in the mammary gland.[14] However, Thrsp-null mice display a greater rate of hepatic de novo lipogenesis when exposed to long-term treatment with thyroid hormone or a

diet promoting lipogenesis, possibly because of compensation by a paralog of THRSP (MID1IP1, also named S14-R or Mig12).[15] Therefore, it remains unclear whether Thrsp promotes lipogenesis in the liver. In the present study, our aim was to elucidate the role of Thrsp in hepatic lipid homeostasis and the mechanism by which LXRs up-regulate Thrsp expression. We provide evidence that hepatic overexpression of Thrsp enhances lipogenesis in livers of C57Bl/6 mice and that hepatic knockdown of Thrsp attenuates liver steatosis in db/db mice. Thrsp expression is induced by LXR agonist TO901317 through an LXR-α–mediated, SREBP-1c–dependent mechanism. TO901317 was purchased from Cayman Chemicals (Ann Arbor, MI). TRIzol was purchased from Invitrogen (Carlsbad, CA). Reverse-transcription and probe-labeling kits were purchased from Promega (Madison, WI).