首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 218 毫秒
1.

Background

Gastric cancer (GC) is the fifth most common malignancy and remains a considerable public health burden worldwide. Genetic variations in genes encoding cytokines and their receptors influence the intensity of the Helicobacter pylori associated inflammatory response, which may contribute to individual differences in the outcome and severity of the disease. Interleukin4 is a typical pleiotropic T helper 2 (Th2) cytokine and is a critical mediator of Th1/Th2 balance. It is involved in the regulation of inflammation-mediated carcinogenesis in human organs, including gastric cancer.

Objective

The present retrospective case control study was undertaken to evaluate the association of IL4 intron 3 VNTR polymorphism with the susceptibility to GC in a south Indian population from Telangana state.

Materials and Methods

A total of 182 patients with diagnosed GC and 326 randomly selected healthy controls were enrolled in the present study. Genomic DNA was extracted from peripheral leukocytes and genotyping was determined by PCR-based assay. Association between genotypes and gastric cancer was examined by unconditional logistic regression analysis.

Result

The variant 3R/2R and 2R/2R genotypes of IL4 exon3 VNTR polymorphism had about 1.9 fold and 3fold increased GC risk, respectively, when compared with 3R/3R genotype [3R/2R vs. 3R/3R: adjusted odds ratio (AOR) = 1.90, 95% confidence interval (CI) = 1.23–2.95 P = 0.004 and 2R/2R vs. 3R/3R: AOR (95%CI) = 2.96 (1.29–6.82), P = 0.011]. Furthermore, a significant increased risk of GC was found for the 2R allele carriers (3R/2R + 2R/2R) compared with the 3R/3R genotype (AOR (95%CI) = 2.04 (1.35–3.10), P = <0.000). The IL4 2R allele frequency was 0.28 among the GC group and 0.18 among the controls, and the difference was statistically significant (P = <0.000).

Conclusion

The present study revealed an association of 2R allele and 2R carrier genotypes in the etiopathogenesis of GC in south Indian population.  相似文献   

2.

Purpose

To study the impact of soluble IL2 receptor (sIL2R), chest x-ray (CxR), and angiotensin-converting enzyme (ACE) as markers for sarcoidosis in uveitis patients.

Design

Retrospective study.

Methods

Serum concentrations of sIL2R and ACE were measured in patients with active uveitis. Those with elevated sIL2R and /or ACE values were examined for suspected systemic sarcoidosis.

Main Outcome Measure

Our main outcome parameters were the specificity and sensitivity of sIL2R, CxR and ACE in screening for ocular sarcoidosis.

Results

We measured 261 patients with uveitis for sarcoidosis using sIL2R and ACE between January 2008 and November 2011; sarcoidosis was been diagnosed using other tests (e.g. computer tomography, brochoalveolar lavage, biopsy) in 41 of 53 patients with elevated sIL2R values (>639 U/ml) and in one patient with normal sIL2R (582 U/ml). Their mean sIL2R value was 1310 U/ml, extending from 582 to 8659 U/ml. Only 9 patients, however, presented elevated ACE (>82 U/l). Their mean ACE value was 116.4 U/l, ranging from 84.1 to 175.5 U/l. IL2R specificity was 94% with 98% sensitivity. In contrast, ACE had a specificity of 99.5%, but a sensitivity of only 22%; the chest x-ray had a specificity of 100% with 50% sensitivity in detecting sarcoidosis. We observed the entire spectrum of uveitis: sixteen patients suffered from anterior, 8 from intermediate, 16 from posterior, and 2 from panuveitis.

Conclusions

An elevated level of soluble IL2R suggests sarcoidosis with uveitis more convincingly than ACE, making sIL2R a more effective marker parameter for sarcoidosis than ACE or chest x-ray in uveitis patients.  相似文献   

3.

BACKGROUND:

A 48bp variable number of tandem repeat (VNTR), in the dopamine receptor D4 (DRD4), has been extensively studied in association with a variety of traits and neuropsychiatric disorders in different ethnic groups; the VNTR has been found to affect receptor binding.

AIMS:

This investigation, for the first time, compared distribution of DRD4 VNTR in different Indian populations from the eastern part of the country, belonging to Indo-Caucasoid and Indo-Mongoloid ethnicity.

MATERIALS AND METHODS:

852 individuals were recruited and divided into six population groups; Brahmin, Kayastha, Scheduled Caste, Mahishya, Muslim and Manipuri (Meitei). Allele and genotype frequencies were compared among groups as well as with data available for south-western Indian population.

RESULTS:

A total of six alleles (2-7-repeats) were observed, of which the 4-repeat (4R) was most frequent. Gross genetic dissimilarities were noticed between the Indo-Caucasoid and Indo-Mongoloid ethnic groups. Muslim group lacked 5R and 7R, while Manipuri group exhibited a very high frequency of 2R. Populations from eastern India revealed lower 7R frequencies as compared to the south-western populations.

CONCLUSIONS:

The DRD4 VNTR has been reported to play important role in cognition and alleles with higher repeats have been found to be associated with novelty seeking and personality traits. The present comparative analysis of different eastern Indian population would be helpful in extending our knowledge on this particular DRD4 variant. It will also be useful in understanding the behavioural differences between populations in the light of their genetic make up.  相似文献   

4.

Objectives

To study the value of assessing renal masses using different methods in parameter approaches and to determine whether BOLD MRI is helpful in differentiating RCC from benign renal masses, differentiating clear-cell RCC from renal masses other than clear-cell RCC and determining the tumour grade.

Methods

Ninety-five patients with 139 renal masses (93 malignant and 46 benign) who underwent abdominal BOLD MRI were enrolled. R2* values were derived from the largest cross-section (R2*largest) and from the whole tumour (R2*whole). Intra-observer and inter-observer agreements were analysed based on two measurements by the same observer and the first measurement from each observer, respectively, and these agreements are reported with intra-class correlation coefficients and 95% confidence intervals. The diagnostic value of the R2* value in the evaluation was assessed with receiver-operating characteristic analysis.

Results

The intra-observer agreement was very good for R2*largest and R2*whole (all > 0.8). The inter-observer agreement of R2*whole (0.75, 95% confidence interval: 0.69~0.79) was good and was significantly improved compared with the R2*largest (0.61, 95% confidence interval: 0.52~0.68), as there was no overlap in the 95% confidence interval of the intra-class correlation coefficients. The diagnostic value in differentiating renal cell carcinoma from benign lesions with R2*whole (AUC=0.79/0.78[observer1/observer2]) and R2*largest (AUC=0.75[observer1]) was good and significantly higher (p=0.01 for R2*largest[observer2] vs R2*whole[observer2], p<0.01 for R2*whole[observer1] vs R2*largest[observer2]) than R2*largest for observer 2 (AUC=0.64). For the grading of clear-cell RCC, both R2*whole and R2*largest were good (all > 0.7) and were not significantly different (p=0.89/0.93 for R2*largest vs R2*whole[observer1/observer2], 0.96 for R2*whole[observer1] vs R2*largest[observer2] and 0.96 for R2*whole [observer2] vs R2*largest[observer1]).

Conclusions

BOLD MRI could provide a feasible parameter for differentiating renal cell carcinoma from benign renal masses and for predicting clear-cell renal cell carcinoma grading. Compared with the largest cross-section, assessing the whole tumour provides better inter-observer agreement in parameter measurement for differentiating renal cell carcinoma from benign renal masses.  相似文献   

5.

Background

Box C/D snoRNPs, which are typically composed of box C/D snoRNA and the four core protein components Nop1, Nop56, Nop58, and Snu13, play an essential role in the modification and processing of pre-ribosomal RNA. The highly conserved R2TP complex, comprising the proteins Rvb1, Rvb2, Tah1, and Pih1, has been shown to be required for box C/D snoRNP biogenesis and assembly; however, the molecular basis of R2TP chaperone-like activity is not yet known.

Results

Here, we describe an unexpected finding in which the activity of the R2TP complex is required for Nop58 protein stability and is controlled by the dynamic subcellular redistribution of the complex in response to growth conditions and nutrient availability. In growing cells, the complex localizes to the nucleus and interacts with box C/D snoRNPs. This interaction is significantly reduced in poorly growing cells as R2TP predominantly relocalizes to the cytoplasm. The R2TP-snoRNP interaction is mainly mediated by Pih1.

Conclusions

The R2TP complex exerts a novel regulation on box C/D snoRNP biogenesis that affects their assembly and consequently pre-rRNA maturation in response to different growth conditions.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-014-0404-4) contains supplementary material, which is available to authorized users.  相似文献   

6.
7.

Objective

The presence of autoantibodies with adrenergic and cholinergic activity, capable of triggering neurotransmitter receptor-mediated effects, has been associated with pathogenesis in T. cruzi-infected hosts. The goal of this study was to investigate the production of anti-M2 muscarinic receptor autoantibodies (Anti-M2R AAbs) as well as the IFN-γ profile in children at the early stage of Chagas disease, and to examine whether trypanocidal chemotherapy with benznidazole (BZ) could modify both response patterns.

Methods

This study comprised 30 T. cruzi-infected children (mean age: 13.8 years) and 19 uninfected controls (mean age: 12.7 years). Infected patients were treated with BZ and followed-up. Blood samples collected at diagnosis-T0, end of treatment-T1, and six months later-T2 were analysed by ELISA for detection of Anti-M2R AAbs and circulating levels of IFN-γ.

Results

At T0, anti-M2R AAbs were demonstrated in 56.7% of T. cruzi-infected patients, whereas uninfected controls were 100% negative. The average age of Anti-M2R AAbs+ patients was higher than that from negative population. Infected children also displayed significantly stronger serum IFN-γ responses than controls. Upon BZ treatment, a significant linear decreasing trend in Anti-M2R AAb reactivity was recorded throughout the follow-up, with 29.7–88.1% decrease at T2. IFN-γ circulating levels also declined by T2.

Conclusion

Anti-M2R AAbs and IFN-γ raise early during chagasic infection in children and are downmodulated by BZ therapy. These findings reinforce the usefulness of early BZ treatment not only to eliminate the parasite but also to reduce potentially pathogenic immune responses.  相似文献   

8.

Objectives

The effects of AT1 receptor blocker, telmisartan, and the ACE inhibitor, ramipril, were tested head-to head and in combination on stroke prevention in hypertensive rats and on potential neuroprotection in acute cerebral ischemia in normotensive rats.

Methods

Prevention study: Stroke-prone spontaneously hypertensive rats (SHR-SP) were subjected to high salt and randomly assigned to 4 groups: (1) untreated (NaCl, n = 24), (2) telmisartan (T; n = 27), (3) ramipril (R; n = 27) and (4) telmisartan +ramipril (T+R; n = 26). Drug doses were selected to keep blood pressure (BP) at 150 mmHg in all groups. Neurological signs and stroke incidence at 50% mortality of untreated SHR-SP were investigated. Intervention study: Normotensive Wistar rats were treated s.c. 5 days prior to middle cerebral artery occlusion (MCAO) for 90 min with reperfusion. Groups (n = 10 each): (1) sham, (2) vehicle (V; 0,9% NaCl), (3) T (0,5 mg/kg once daily), (4) R (0,01 mg/kg twice daily), (5) R (0,1 mg/kg twice daily) or (6) T (0,5 mg/kg once daily) plus R (0,01 mg/kg twice daily). Twenty-four and 48 h after MCAO, neurological outcome (NO) was determined. Forty-eight h after MCAO, infarct volume by MRI, neuronal survival, inflammation factors and neurotrophin receptor (TrkB) were analysed.

Results

Stroke incidence was reduced, survival was prolonged and neurological outcome was improved in all treated SHR-SP with no differences between treated groups. In the acute intervention study, T and T+R, but not R alone, improved NO, reduced infarct volume, inflammation (TNFα), and induced TrkB receptor and neuronal survival in comparison to V.

Conclusions

T, R or T+R had similar beneficial effects on stroke incidence and NO in hypertensive rats, confirming BP reduction as determinant factor in stroke prevention. In contrast, T and T+R provided superior neuroprotection in comparison to R alone in normotensive rats with induced cerebral ischemia.  相似文献   

9.
Chen S  Owens GC  Edelman DB 《PloS one》2008,3(7):e2804

Background

The trafficking of mitochondria within neurons is a highly regulated process. In an earlier study, we found that serotonin (5-HT), acting through the 5-HT1A receptor subtype, promotes axonal transport of mitochondria in cultured hippocampal neurons by increasing Akt activity, and consequently decreasing glycogen synthase kinase (GSK3β) activity. This finding suggests a critical role for neuromodulators in the regulation of mitochondrial trafficking in neurons. In the present study, we investigate the effects of a second important neuromodulator, dopamine, on mitochondrial transport in hippocampal neurons.

Methodology/Principal Findings

Here, we show that dopamine, like 5-HT, regulates mitochondrial motility in cultured hippocampal neurons through the Akt-GSK3β signaling cascade. But, in contrast to the stimulatory effect of 5-HT, administration of exogenous dopamine or bromocriptine, a dopamine 2 receptor (D2R) agonist, caused an inhibition of mitochondrial movement. Moreover, pretreatment with bromocriptine blocked the stimulatory effect of 5-HT on mitochondrial movement. Conversely, in cells pretreated with 5-HT, no further increases in movement were observed after administration of haloperidol, a D2R antagonist. In contrast to the effect of the D2R agonist, addition of SKF38393, a dopamine 1 receptor (D1R) agonist, promoted mitochondrial transport, indicating that the inhibitory effect of dopamine was actually the net summation of opposing influences of the two receptor subtypes. The most pronounced effect of dopamine signals was on mitochondria that were already moving directionally. Western blot analysis revealed that treatment with either a D2R agonist or a D1R antagonist decreased Akt activity, and conversely, treatment with either a D2R antagonist or a D1R agonist increased Akt activity.

Conclusions/Significance

Our observations strongly suggest a role for both dopamine and 5-HT in regulating mitochondrial movement, and indicate that the integrated effects of these two neuromodulators may be important in determining the distribution of energy sources in neurons.  相似文献   

10.

Background

Hypoxic pulmonary vasoconstriction (HPV) is an essential mechanism of the lung that matches blood perfusion to alveolar ventilation to optimize gas exchange. Recently we have demonstrated that acute but not sustained HPV is critically dependent on the classical transient receptor potential 6 (TRPC6) channel. However, the mechanism of TRPC6 activation during acute HPV remains elusive. We hypothesize that a diacylglycerol (DAG)-dependent activation of TRPC6 regulates acute HPV.

Methods

We investigated the effect of the DAG analog 1-oleoyl-2-acetyl-sn-glycerol (OAG) on normoxic vascular tone in isolated perfused and ventilated mouse lungs from TRPC6-deficient and wild-type mice. Moreover, the effects of OAG, the DAG kinase inhibitor R59949 and the phospholipase C inhibitor U73122 on the strength of HPV were investigated compared to those on non-hypoxia-induced vasoconstriction elicited by the thromboxane mimeticum U46619.

Results

OAG increased normoxic vascular tone in lungs from wild-type mice, but not in lungs from TRPC6-deficient mice. Under conditions of repetitive hypoxic ventilation, OAG as well as R59949 dose-dependently attenuated the strength of acute HPV whereas U46619-induced vasoconstrictions were not reduced. Like OAG, R59949 mimicked HPV, since it induced a dose-dependent vasoconstriction during normoxic ventilation. In contrast, U73122, a blocker of DAG synthesis, inhibited acute HPV whereas U73343, the inactive form of U73122, had no effect on HPV.

Conclusion

These findings support the conclusion that the TRPC6-dependency of acute HPV is induced via DAG.  相似文献   

11.

Background

Lung protective mechanical ventilation (MV) is the corner stone of therapy for ARDS. However, its use may be limited by respiratory acidosis.This study explored feasibility of, effectiveness and safety of low flow extracorporeal CO2 removal (ECCO2R).

Methods

This was a prospective pilot study, using the Abylcap® (Bellco) ECCO2R, with crossover off-on-off design (2-h blocks) under stable MV settings, and follow up till end of ECCO2R. Primary endpoint for effectiveness was a 20% reduction of PaCO2 after the first 2-h. Adverse events (AE) were recorded prospectively.We included 10 ARDS patients on MV, with PaO2/FiO2?<?150 mmHg, tidal volume?≤?8 mL/kg with positive end-expiratory pressure ≥?5 cmH2O, FiO2 titrated to SaO2 88–95%, plateau pressure ≥?28 cmH2O, and respiratory acidosis (pH <7.25).

Results

After 2-h of ECCO2R, 6 patients had a ≥?20% decrease in PaCO2 (60%); PaCO2 decreased 28.4% (from 58.4 to 48.7 mmHg, p?=?0.005), and pH increased (1.59%, p?=?0.005). ECCO2R was hemodynamically well tolerated. During the whole period of ECCO2R, 6 patients had an AE (60%); bleeding occurred in 5 patients (50%) and circuit thrombosis in 3 patients (30%), these were judged not to be life threatening.

Conclusions

In ARDS patients, low flow ECCO2R significantly reduced PaCO2 after 2 h, Follow up during the entire ECCO2R period revealed a high incidence of bleeding and circuit thrombosis.

Trial registration

https://clinicaltrials.gov identifier: NCT01911533, registered 23 July 2013.
  相似文献   

12.

Book Review

Photosynthesis: Molecular biology and bioenergeticsG.S. Singhal, J. Barber, R.A. Dilley, Govindjee, R. Haselkorn and P. Mohanty (Eds), Proceedings of the International Workshop on Application of Molecular Biology and Bioenergetics of Photosynthesis. Berlin, Heidelberg, New York, London, Paris, Tokyo, Hong Kong and Narosa: Springer-Verlag, 1989. xiv+441 pages. DM 148,00. ISBN 3-540-50451-6  相似文献   

13.

Introduction

Low-to-moderate intensity exercise improves muscle contractile properties and endurance capacity in multiple sclerosis (MS). The impact of high intensity exercise remains unknown.

Methods

Thirty-four MS patients were randomized into a sedentary control group (SED, n = 11) and 2 exercise groups that performed 12 weeks of a high intensity interval (HITR, n = 12) or high intensity continuous cardiovascular training (HCTR, n = 11), both in combination with resistance training. M.vastus lateralis fiber cross sectional area (CSA) and proportion, knee-flexor/extensor strength, body composition, maximal endurance capacity and self-reported physical activity levels were assessed before and after 12 weeks.

Results

Compared to SED, 12 weeks of high intensity exercise increased mean fiber CSA (HITR: +21±7%, HCTR: +23±5%). Furthermore, fiber type I CSA increased in HCTR (+29±6%), whereas type II (+23±7%) and IIa (+23±6%,) CSA increased in HITR. Muscle strength improved in HITR and HCTR (between +13±7% and +45±20%) and body fat percentage tended to decrease (HITR: -3.9±2.0% and HCTR: -2.5±1.2%). Furthermore, endurance capacity (Wmax +21±4%, time to exhaustion +24±5%, VO2max +17±5%) and lean tissue mass (+1.4±0.5%) only increased in HITR. Finally self-reported physical activity levels increased 73±19% and 86±27% in HCTR and HITR, respectively.

Conclusion

High intensity cardiovascular exercise combined with resistance training was safe, well tolerated and improved muscle contractile characteristics and endurance capacity in MS.

Trial Registration

ClinicalTrials.gov NCT01845896  相似文献   

14.
15.
Mutations were studied in phenylalanine hydroxylase gene of phenylketonuria patients from Kemerovo oblast and Altaiskii krai (15 and 2 families, respectively). The following mutations were identified in exons of this gene: R408W, R261Q, R243Q, R158Q, Y414C, Y386C, P281L, Y168H, R68S (lead to amino acid substitutions), R243X (leads to stop codon formation), and three splice site mutations (IVS12nt1g a, IVS2nt-13t g, IVS7nt 1g a).  相似文献   

16.

Book reviews

Conjugated plant hormones: Structure, metabolism and functionK. Schreiber, H.R. Schütte and G. Sembdner (Eds.), proceedings of the international symposium on conjugated plant hormones. Structure, metabolism and function. Berlin: VEB Deutscher Verlag der Wissenschaften, 1987. 405 pages  相似文献   

17.

Background

Drugs of abuse elevate brain dopamine levels, and, in vivo, chronic drug use is accompanied by a selective decrease in dopamine D2 receptor (D2R) availability in the brain. Such a decrease consequently alters the ratio of D1R∶D2R signaling towards the D1R. Despite a plethora of behavioral studies dedicated to the understanding of the role of dopamine in addiction, a molecular mechanism responsible for the downregulation of the D2R, in vivo, in response to chronic drug use has yet to be identified.

Methods and Findings

Ethics statement: All animal work was approved by the Gallo Center IACUC committee and was performed in our AAALAC approved facility. In this study, we used wild type (WT) and G protein coupled receptor associated sorting protein-1 (GASP-1) knock out (KO) mice to assess molecular changes that accompany cocaine sensitization. Here, we show that downregulation of D2Rs or upregulation of D1Rs is associated with a sensitized locomotor response to an acute injection of cocaine. Furthermore, we demonstrate that disruption of GASP-1, that targets D2Rs for degradation after endocytosis, prevents cocaine-induced downregulation of D2Rs. As a consequence, mice with a GASP-1 disruption show a reduction in the sensitized locomotor response to cocaine.

Conclusions

Together, our data suggests that changes in the ratio of the D1R∶D2R could contribute to cocaine-induced behavioral plasticity and demonstrates a role of GASP-1 in regulating both the levels of the D2R and cocaine sensitization.  相似文献   

18.

Book reviews

Improving vegetatively propagated cropsA.J. Abbott and R.K. Atkin (Eds.), London: Academic Press, 1987. xvii + 416 pages. £37.00. 0-12-041410-4  相似文献   

19.

OBJECTIVES:

The angiotensin II protein is a vasoconstrictor that exerts most of its influence through the angiotensin II type 1 receptor (AT1R). Inconsistent association between the A1166C polymorphism of the AT1R gene and hypertension has been reported among various populations but not among the peoples of Calabar and Uyo. This study was designed to determine the frequency of the A1166C polymorphism of the AT1R gene and its association with hypertension in a sample population of Calabar and Uyo.

MATERIALS AND METHODS:

A population-based case control design consisting of total of 1224 participants, 612 each of patients and controls were randomly recruited from hypertension clinics and the general population. Genotyping of the A1166C allele of the AT1R gene to identify variants was performed using polymerase chain reaction and restriction enzyme digestion. Multiple regressions were applied to test whether the A1166 genotypes were predictors of hypertension.

RESULTS:

99% of the study population had the wild type AA genotype, and 1% was AC heterozygous carriers of the A1166C polymorphism.

CONCLUSION:

The A1166C polymorphism was not a predictor of hypertension in the sample population of Calabar and Uyo.  相似文献   

20.
Walter Gams 《Mycopathologia》2004,158(3):395-396

Book Review

Book Review:R.J. Cole, B.B. Jarvis and M.A. Schweikert eds.Handbook of Secondary Fungal metabolites, AcademicPress, UK, 2003. 2544 pp. $299.95.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号