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51.
Contribution of VEGF and PEDF to choroidal angiogenesis: a need for balanced expressions 总被引:3,自引:0,他引:3
Ocular angiogenesis may lead to visual impairment and even irreversible blindness in people of all ages worldwide. Choroidal neovascularization (CNV), a major clinical complication of ocular angiogenesis, is an important cause of vision loss that affects a large number of people. Physiological angiogenesis is tightly controlled by a balance in the expression of angiogenic and anti-angiogenic factors. While the underlying mechanism of CNV is complex, it is attributed to an upset in this balance. The vascular endothelial growth factor (VEGF) is essential in the development of CNV as one of the most potent angiogenic stimulators and vascular permeability factors. Pigment epithelium derived factor (PEDF) is a strong inhibitor of angiogenesis with high neuroprotective effects. VEGF and PEDF both possess multiple biological activities and functions that affect a large variety of tissue cells of the eye and other organs. Inappropriate expression levels are associated with many diseases involving neovascularization. This paper describes the unbalanced expressions of VEGF and PEDF as a cause of CNV. Based on the respective angiogenic and anti-angiogenic properties of VEGF and PEDF, experimental models have been devised to genetically reduce VEGF or enhance PEDF to achieve therapeutic effects. Gene therapy for CNV is promising and is under intensive research. 相似文献
52.
Frontal cortex lesions eliminate the clock speed effect of dopaminergic drugs on interval timing 总被引:2,自引:0,他引:2
Meck WH 《Brain research》2006,1108(1):157-167
Behavioral and pharmacological challenges using methamphetamine (MAP-0.5 and 1.0 mg/kg, i.p.), haloperidol (HAL-0.12 mg/kg, i.p.), and sulfated cholecystokinin octapeptide (CCK-0.05 and 0.1 mg/kg, i.p.) were used to evaluate the effects of excitotoxic lesions of cholinergic cell bodies in the medial septal area and the nucleus basalis magnocellularis, radiofrequency lesions of the fimbria-fornix, and aspiration lesions of the frontal cortex on interval timing in rats trained on a 40-s peak-interval procedure. Results demonstrated that lesions of the nucleus basalis magnocellularis and frontal cortex selectively reduced the modulatory control of clock speed which is likely mediated by dopamine D(2) receptors located on cortico-striatal neurons. 相似文献
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54.
During the CNV recorded in a simple auditory working memory task, task-specific decrease of the relative delta band and a transient increase of the absolute theta band were seen, accompanied by an increase of the absolute alpha1 and alpha2 bands in the posterior region. The decreased delta power probably corresponds to increased task-evoked arousal, whereas the transient theta power increase corresponds to working memory demand and possibly to the orienting response. The increased alpha1 and alpha2 power may be a manifestation of a top-down mechanism revealing control over the execution of a response. The area-specific, task-related, and frequency-dependent changes of EEG complexity measures indicate frontally increasing complexity during the early part of the CNV in the beta frequency bands, which underscores the importance of this region in the mechanisms of anticipatory behavior. 相似文献
55.
Groth M Szafranski K Taudien S Huse K Mueller O Rosenstiel P Nygren AO Schreiber S Birkenmeier G Platzer M 《Human mutation》2008,29(10):1247-1254
One unexpected feature of the human genome is the high structural variability across individuals. Frequently, large regions of the genome show structural polymorphisms and many vary in their abundance. However, accurate methods for the characterization and typing of such copy number variations (CNV) are needed. The defensin cluster at the human region 8p23.1 is one of the best studied CNV regions due to its potential clinical relevance for innate immunity, inflammation, and cancer. The region can be divided into two subclusters, which harbor predominantly either alpha- or beta-defensin genes. Previous studies assessing individual copy numbers gave different results regarding whether the complete beta-defensin cluster varies or only particular genes therein. We applied multiplex ligation-dependent probe amplification (MLPA) to measure defensin locus copy numbers in 42 samples. The data show strict copy number concordance of all 10 loci typed within the beta-defensin cluster in each individual, while seven loci within the alpha-defensin cluster are consistently found as single copies per chromosome. The exception is DEFA3, which is located within the alpha-defensin cluster and was found to also differ in copy number interindividually. Absolute copy numbers ranged from two to nine for the beta-defensin cluster and zero to four for DEFA3. The CNV-typed individuals, including HapMap samples, are publicly available and may serve as a universal reference for absolute copy number determination. On this basis, MLPA represents a reliable technique for medium- to high-throughput typing of 8p23.1 defensin CNV in association studies for diverse clinical phenotypes. 相似文献
56.
Common neurodevelopmental disorders (including autism, speech and language delay, schizophrenia, epilepsy and intellectual disability) have complex aetiology, which is predominantly genomic, but also environmental in origin. They share a paradox, in that high heritability is matched by lowered fecundity, placing them under negative genetic selection. This implicates variants of recent origin, such as de novo mutations or common, very low-risk polymorphisms that escape negative selection. High or moderate risk variants have been discovered by chromosome analysis, genome sequencing and copy number variant (CNV) detection, including a 3Mb deletion causing 22q11.2 deletion syndrome (Velo-Cardio-Facial Syndrome) that has penetrance of up to 50% for schizophrenia. More recently, rare, recurrent and often de novo pathogenic CNVs, including deletions at NRXN1, 1q21.2, 15q11.2 and 15q13.3, 16p11.2 and duplications at VIPR2 and 16p13.11, have also been discovered. These have several unique features that differentiate them from Mendelian disease mutations in that they have incomplete penetrance, with moderate-to-high odds ratios for risk, and show diagnostic pleiotropy, increasing risk across the neurodevelopmental disorder spectrum. Some are also syndromic, with characteristic features such as facial dysmorphology, and other specific risks such as aortic dissection or obesity, implying that they might be better classified as distinct diagnoses. The discovery of pathogenic CNVs provide new opportunities for translation leading to patent benefit, including improvements in clinical genetic diagnosis and genetic counselling, the possibility of clinician decision-making tools for risk prediction, and the identification of drug targets and implementation of personalised medicine using stratification by genotype. 相似文献
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58.
《Clinical colorectal cancer》2019,18(3):175-182
BackgroundTherapy targeting human epidermal growth factor receptor 2 (HER2, also known as ERBB2) is an effective approach for HER2-positive metastatic colorectal cancer (mCRC). HER2 status is typically determined using immunohistochemistry and fluorescence in situ hybridization. Circulating tumor DNA (ctDNA) enables noninvasive detection of gene mutations and copy number alterations including HER2 amplification.Materials and MethodsWe screened 351 patients with mCRC and studied the clinicopathologic characteristics of HER2-positive mCRC. HER2 expression in tumor samples measured with immunohistochemistry and fluorescence in situ hybridization was compared with HER2 copy number variation in plasma ctDNA detected by targeted sequence capture covering exons of 170 genes. We also examined the correlation between changes in tumor burden in ctDNA and antitumor response by imaging evaluation during the treatment course.ResultsPositive HER2 status was observed in 12 (3.4%) patients (7 males and 5 females), with a median age of 56 years. The HER2 concordance rate between tumor samples and ctDNA was 66.7% (20/30). Changes in tumor burden in ctDNA during the treatment course correlated with responses on imaging.ConclusionsDetection of HER2 copy number variation in ctDNA may be an alternative option for noninvasive determination of HER2 status. Tumor burden changes in ctDNA were consistent with imaging evaluation. 相似文献
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60.
T. S. Prevec A. Berić 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1991,84(3):643-648
Summary An objective method developed to measure the threshold of light touch perception using contingent negative variation (CNV) is described. The light touch stimulus was a slight indentation of the skin produced through a displacement controlled stimulating probe (tip diameter of 2 mm). It was applied as the conditioning (S1) stimulus of the classical CNV paradigm of S1, S2, and R. To increase the CNV amplitude, the S2 stimulus was either a red or a yellow LED. The subjects were required to respond to only one of two by pressing a button. When the light touch stimulus was perceived, the CNV was recorded in all 19 healthy adult volunteers. In 14 of them, a systematic determination of the threshold of the ball of the thumb and index finger, thenar, hypothenar, face, shoulder, anterior thigh, foot dorsum and great toe ball, have been done. The thresholds of the light touch perception as defined by objective CNV measurement are very close to the results of the subjective psychophysiological determinations in normals. The amplitude of the averaged CNV (12 responses) started to decrease when stimulus intensity was reduced to the point that the subjects were able to perceive only a fraction of the presented touch stimuli. We believe, therefore, that the objective CNV determination of the light touch perception threshold is precise and sensitive enough to be used in research as well as in clinical applications. 相似文献