262 research outputs found

    Angiotensin-Converting Enzyme Genotype and Peripheral Arterial Disease in Diabetic Patients

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    We investigated the effect of traditional risk factors (hypertension, dyslipidemia and smoking) on the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and peripheral arterial disease (PAD) in 945 (454 men and 491 women) Taiwanese type 2 diabetic patients with a mean age of 63.5 (SD: 11.4) years. Among them, 81 (31 men and 50 women) had PAD (ankle-brachial index <0.9). The adjusted odds ratios (95% confidence intervals) were 2.48 (1.18–5.21), 1.69 (1.00–2.85) and 1.64 (1.12–2.39), respectively, for recessive (DD versus II + ID), dominant (DD + ID versus II) and additive (II = 0, ID = 1 and DD = 2) models. While analyzing the interaction between DD and the individual risk factor of hypertension, smoking and dyslipidemia, patients with the risk factor and with DD had the highest risk compared to referent patients without the risk factor and with II/ID. The respective adjusted odds ratios were 5.41 (2.05–14.31), 7.38 (1.87–29.06) and 4.64 (1.70–12.64). We did not find a significant interaction between DD and any of the risk factors under multiplicative or additive scale. In conclusion, traditional risk factors (hypertension, smoking and dyslipidemia) play an important role in the association between ACE genotypes and PAD. Patients with DD genotype and traditional risk factors are at the highest risk

    Growth rate regulation of lac operon expression in Escherichia coli is cyclic AMP dependent

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    AbstractIn contrast to the ribosomal RNA gene expression increasing with growth rate, transcription of the lac operon is downregulated by cell growth rate. In continuous culture, growth rate regulation of lac promoter was independent of carbon substrate used and its location on the chromosome. Since the lac operon is activated by cyclic adenosine monophosphate (cAMP), which decreases with increasing cell growth rate, expression of plac-lacZ reporter fusion was analyzed in cya mutant under various growth conditions. The results demonstrated that expression of plac-lacZ in cya mutant was both lower and growth rate independent. In addition, ppGpp (guanosine tetraphosphate) was not involved in the mechanism of growth rate regulation of the lac promoter. Thus, the results of this study indicate that cAMP mediates the growth rate-dependent regulation of lac operon expression in Escherichia coli

    Integrin-mediated membrane blebbing is dependent on the NHE1 and NCX1 activities.

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    Integrin-mediated signal transduction and membrane blebbing have been well studied to modulate cell adhesion, spreading and migration^1-6^. However, the relationship between membrane blebbing and integrin signaling has not been explored. Here we show that integrin-ligand interaction induces membrane blebbing and membrane permeability change. We found that sodium-proton exchanger 1 (NHE1) and sodium-calcium exchanger 1 (NCX1) are located in the membrane blebbing sites and inhibition of NHE1 disrupts membrane blebbing and decreases membrane permeability change. However, inhibition of NCX1 enhances cell blebbing to cause cell swelling which is correlated with an intracellular sodium accumulation induced by NHE17. These data suggest that sodium influx induced by NHE1 is a driving force for membrane blebbing growth, while sodium efflux induced by NCX1 in a reverse mode causes membrane blebbing retraction. Together, these data reveal a novel function of NHE1 and NCX1 in membrane permeability change and blebbing and provide the link for integrin signaling and membrane blebbing

    Deletions of Chromosome 1p and 15q are Associated with Aggressiveness of Gastrointestinal Stromal Tumors

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    Background/PurposeSite-dependent profiles of chromosome imbalances (CIs) have been reported in gastrointestinal stromal tumors (GISTs). However, the role of specific CIs in association with metastasis is not clear.MethodsThirteen resected liver metastatic GISTs, including seven from the stomach and six from the small intestine, were analyzed using comparative genomic hybridization (CGH). The CIs associated with metastatic risk were assessed by comparing them with those identified in our previous study of 25 primary GISTs, including 14 from the stomach and 11 from the small intestine.ResultsSynchronous detection of liver metastasis was found more often in patients with intestinal than gastric GIST (5/6 vs. 2/7, p = 0.048). When compared with the primary tumors, the CI profile of liver metastases was similar in the intestinal group, but became more complex in the gastric group. Deletions of chromosomes 1p and 15q were very common (> 80%) in primary and metastatic tumors of the intestinal group, and exhibited a trend towards increase in the metastatic tumors of the gastric group. Both groups had a doubling in the frequency of 22q deletion in the liver metastases, which was not significantly different. Other CIs, including 9p deletion, increased significantly in the liver metastases of the gastric group, but not in the intestinal group.ConclusionOur results, together with clinical findings, indicated a CGH profile associated with the intrinsic aggressiveness of the GISTs. Deletion of 1p and 15q play a critical role in the acquisition of aggressiveness during early GIST development

    UPANets: Learning from the Universal Pixel Attention Networks

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    Among image classification, skip and densely-connection-based networks have dominated most leaderboards. Recently, from the successful development of multi-head attention in natural language processing, it is sure that now is a time of either using a Transformer-like model or hybrid CNNs with attention. However, the former need a tremendous resource to train, and the latter is in the perfect balance in this direction. In this work, to make CNNs handle global and local information, we proposed UPANets, which equips channel-wise attention with a hybrid skip-densely-connection structure. Also, the extreme-connection structure makes UPANets robust with a smoother loss landscape. In experiments, UPANets surpassed most well-known and widely-used SOTAs with an accuracy of 96.47% in Cifar-10, 80.29% in Cifar-100, and 67.67% in Tiny Imagenet. Most importantly, these performances have high parameters efficiency and only trained in one customer-based GPU. We share implementing code of UPANets in https://github.com/hanktseng131415go/UPANets

    Procalcitonin as a marker of bacterial infection in the emergency department: an observational study

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    INTRODUCTION: Procalcitonin (PCT) has been proposed as a marker of infection in critically ill patients; its level is related to the severity of infection. We evaluated the value of PCT as a marker of bacterial infection for emergency department patients. METHODS: This prospective observational study consecutively enrolled 120 adult atraumatic patients admitted through the emergency department of a 3000-bed tertiary university hospital in May 2001. Fifty-eight patients were infected and 49 patients were not infected. The white blood cell counts, the serum C-reactive protein (CRP) level (mg/l), and the PCT level (ng/ml) were compared between the infected and noninfected groups of patients. RESULTS: A white blood cell count >12,000/mm(3 )or <4000/mm(3 )was present in 36.2% of the infected patients and in 18.4% of the noninfected patients. The best cut-off serum levels for PCT and CRP, identified using the Youden's Index, were 0.6 ng/ml and 60 mg/l, respectively. Compared with CRP, PCT had a comparable sensitivity (69.5% versus 67.2%), a lower specificity (64.6% versus 93.9%), and a lower area under the receiver operating characteristic curve (0.689 versus 0.879). PCT levels, but not CRP levels, were significantly higher in bacteremic and septic shock patients. Multivariate logistic regression identified that a PCT level ≥ 2.6 ng/ml was independently associated with the development of septic shock (odds ratio, 38.3; 95% confidence interval, 5.6–263.5; P < 0.001). CONCLUSIONS: PCT is not a better marker of bacterial infection than CRP for adult emergency department patients, but it is a useful marker of the severity of infection

    miRNAMap: genomic maps of microRNA genes and their target genes in mammalian genomes

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    Recent work has demonstrated that microRNAs (miRNAs) are involved in critical biological processes by suppressing the translation of coding genes. This work develops an integrated database, miRNAMap, to store the known miRNA genes, the putative miRNA genes, the known miRNA targets and the putative miRNA targets. The known miRNA genes in four mammalian genomes such as human, mouse, rat and dog are obtained from miRBase, and experimentally validated miRNA targets are identified in a survey of the literature. Putative miRNA precursors were identified by RNAz, which is a non-coding RNA prediction tool based on comparative sequence analysis. The mature miRNA of the putative miRNA genes is accurately determined using a machine learning approach, mmiRNA. Then, miRanda was applied to predict the miRNA targets within the conserved regions in 3′-UTR of the genes in the four mammalian genomes. The miRNAMap also provides the expression profiles of the known miRNAs, cross-species comparisons, gene annotations and cross-links to other biological databases. Both textual and graphical web interface are provided to facilitate the retrieval of data from the miRNAMap. The database is freely available at

    A Chinese Herbal Decoction, Modified Yi Guan Jian, Induces Apoptosis in Hepatic Stellate Cells through an ROS-Mediated Mitochondrial/Caspase Pathway

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    The Chinese herb modified Yi Guan Jian (mYGJ) is an effective regimen that is usually used in outpatients with chronic liver diseases such as fibrosis and cirrhosis. However, the mechanism for the action of mYGJ on liver fibrosis is not yet clear. In this study, we found that mYGJ induced hepatic stellate cells (HSCs) apoptosis concomitant with the downregulation of Bcl-2 expression and slight elevation of Bax level. Moreover, the reactive oxygen species (ROS) were generated in the early stages of mYGJ-induced HSCs apoptosis to facilitate calcium and cytochrome c release from the mitochondria to cytosol. Subsequently, caspase 9 and caspase 3 were activated. Furthermore, the activation of ER stress-associated caspase 12 in HSCs was also evaluated. Together, we report the first evidence-based study to demonstrate that mYGJ decoction induces HSCs apoptosis through ROS accumulation and the intrinsic apoptosis pathway. These findings provide rationale for further clinical investigation of traditional Chinese medicine recipes against liver fibrosis

    Long-term follow-up of patients with surgical intractable acromegaly after linear accelerator radiosurgery

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    Background/PurposeRadiotherapy is a crucial treatment for acromegalic patients with growth hormone (GH)-secreting pituitary tumors. However, its effect takes time. We retrospectively reviewed the long-term outcome of linear accelerator stereotactic radiosurgery (LINAC SRS) for patients with acromegaly from the perspective of biochemical remission and associated factors.MethodsTwenty-two patients presenting with residual or recurrent (GH)-secreting functional pituitary tumor between 1994 and 2004 who received LINAC SRS were enrolled and followed up for at least 3 years. Residual or recurrent tumor was defined as persistent elevated GH or insulin-like growth factor-1 (IGF-1) level and image-confirmed tumor after previous surgical treatment. Biochemical remission was defined as fasting GH less than 2.5 ng/mL with normal sex-and-age adjusted IGF-1.ResultsThe mean follow-up period was 94.7 months (range 36–161 months). Overall mean biochemical remission time was 53 months (median 30 months). Biochemical control was achieved in 15 patients (68.2%) over the follow up period. One patient experienced recurrence after SRS and underwent another operation. Initial GH at diagnosis and pre-SRS GH correlated with biochemical control (p = 0.005 and p < 0.0001, respectively). Further evaluation demonstrated that biochemical control stabilized after 7.5 years. Overall post-SRS hormone deficit persisted in five patients (22.7%).ConclusionIn comparison to other radiosurgery modalities, LINAC radiosurgery also provides a satisfactory outcome. SRS has maximum effect over the first 2 years and stabilizes after 7.5 years. Moreover, SRS elicits long-term biochemical effects and requires longer follow-up for better biochemical remission
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