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排序方式: 共有309条查询结果,搜索用时 281 毫秒
301.
Girish V Putcha Bassem A Bejjani Stacey Bleoo Jessica K Booker John C Carey Nancy Carson Soma Das Melissa A Dempsey Julie M Gastier-Foster John H Greinwald Marcy L Hoffmann Linda Jo Bone Jeng Margaret A Kenna Ishrag Khababa Margaret Lilley Rong Mao Kasinathan Muralidharan Iris M Otani Heidi L Rehm Fred Schaefer William K Seltzer Elaine B Spector Michelle A Springer Karen E Weck Richard J Wenstrup Stacey Withrow Bai-Lin Wu Maimoona A Zariwala Iris Schrijver 《Genetics in medicine》2007,9(7):413-426
PURPOSE: The aim of the study was to determine the actual GJB2 and GJB6 mutation frequencies in North America after several years of generalized testing for autosomal recessive nonsyndromic sensorineural hearing loss to help guide diagnostic testing algorithms, especially in light of molecular diagnostic follow-up to universal newborn hearing screening. METHODS: Mutation types, frequencies, ethnic distributions, and genotype-phenotype correlations for GJB2 and GJB6 were assessed in a very large North American cohort. RESULTS: GJB2 variants were identified in 1796 (24.3%) of the 7401 individuals examined, with 399 (5.4%) homozygous and 429 (5.8%) compound heterozygous. GJB6 deletion testing was performed in 12.0% (888/7401) of all cases. The >300-kb deletion was identified in only nine individuals (1.0%), all of whom were compound heterozygous for mutations in GJB2 and GJB6. Among a total of 139 GJB2 variants identified, 53 (38.1%) were previously unreported, presumably representing novel pathogenic or benign variants. CONCLUSIONS: The frequency and distribution of sequence changes in GJB2 and GJB6 in North America differ from those previously reported, suggesting a considerable role for loci other than GJB2 and GJB6 in the etiology of autosomal recessive nonsyndromic sensorineural hearing loss, with minimal prevalence of the GJB6 deletion. 相似文献
302.
Rapid glucose-dependent increases in phosphatidic acid and phosphoinositides in rat pancreatic islets 总被引:6,自引:0,他引:6
R V Farese P E DiMarco D E Barnes M A Sabir R E Larson J S Davis A D Morrison 《Endocrinology》1986,118(4):1498-1503
Glucose effects on islet phospholipids were examined during direct incubation or after 3 days of 32P prelabeling in primary culture. In both cases, glucose increased the 32P content of phosphatidic acid (PA), phosphatidylinositol (PI), and polyphosphoinositides (PPI). Glucose-induced increases in PA, PI, and PPI in the culture-prelabeling experiments were evident within 1 min, dose related, and reflective of increases in phospholipid mass, which was confirmed in direct incubations by measurement of PI phosphorus. Thus, in addition to increasing PI-PPI hydrolysis, glucose increases de novo phospholipid synthesis in pancreatic islets. The latter may result from enhanced glycolysis and substrate availability for PA-PI-PPI synthesis, since glyceraldehyde and pyruvic acid also increased PI levels. Our findings raise the possibility that increases in PA, PI, and PPI synthesis could serve as a mechanism to enhance the generation of intracellular mediators, which are purported to regulate insulin secretion. 相似文献
303.
Mislocalization of DNAH5 and DNAH9 in respiratory cells from patients with primary ciliary dyskinesia 总被引:3,自引:0,他引:3
Fliegauf M Olbrich H Horvath J Wildhaber JH Zariwala MA Kennedy M Knowles MR Omran H 《American journal of respiratory and critical care medicine》2005,171(12):1343-1349
RATIONALE: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by recurrent infections of the airways and situs inversus in half of the affected offspring. The most frequent genetic defects comprise recessive mutations of DNAH5 and DNAI1, which encode outer dynein arm (ODA) components. Diagnosis of PCD usually relies on electron microscopy, which is technically demanding and sometimes difficult to interpret. METHODS: Using specific antibodies, we determined the subcellular localization of the ODA heavy chains DNAH5 and DNAH9 in human respiratory epithelial and sperm cells of patients with PCD and control subjects by high-resolution immunofluorescence imaging. We also assessed cilia and sperm tail function by high-speed video microscopy. RESULTS: In normal ciliated airway epithelium, DNAH5 and DNAH9 show a specific regional distribution along the ciliary axoneme, indicating the existence of at least two distinct ODA types. DNAH5 was completely or only distally absent from the respiratory ciliary axoneme in patients with PCD with DNAH5- (n = 3) or DNAI1- (n = 1) mutations, respectively, and instead accumulated at the microtubule-organizing centers. In contrast to respiratory cilia, sperm tails from a patient with DNAH5 mutations had normal ODA heavy chain distribution, suggesting different modes of ODA generation in these cell types. Blinded investigation of a large cohort of patients with PCD and control subjects identified DNAH5 mislocalization in all patients diagnosed with ODA defects by electron microscopy (n = 16). Cilia with complete axonemal DNAH5 deficiency were immotile, whereas cilia with distal DNAH5 deficiency showed residual motility. CONCLUSIONS: Immunofluorescence staining can detect ODA defects, which will possibly aid PCD diagnosis. 相似文献
304.
305.
Irritant and cytotoxic potentiality of six coumarins, isolated for the first time from the roots of Angelica glauca identified as 5,6,7-trimethoxycoumarin, 6-methoxy-7,8-methylenedioxycoumarin, bergapten, decursinol angelate, decursin, and nodakenetin, were investigated. The irritant potential was explored by open mouse ear assay, evaluating their ID(50) after acute and by IU (Irritant units) after chronic effects, while the cytotoxic capability was explored by their LC(50), using brine shrimp (Artemia salina) larvae (nauplii). All the coumarins exhibited well-defined irritancy on mouse's ears, compared with the positive controlled euphorbium reaction and cytotoxic response against brine shrimp larvae, compared with the positive control colchicine. Decursinol angelate and decursin were the most potent and persistent irritant compounds with least ID(50), whose reactions lasted for 48 h. 6-Methoxy-7,8-methylenedioxycoumarin and bergaten revealed an intermediate irritant reactions, while 5,6,7-trimethoxycoumarin and nodakenetin displayed the least irritant and least persistent reactions on mouse ears. Both decursin and decursinol angelate also appeared to be the stronger cytotoxic agents than other coumarins. 5,6,7-trimethoxycoumarin displayed an intermediate cytotoxic behaviour, while other three coumarins, i.e., 6-methoxy-7,8-methylenedioxycoumarin, bergapten, and nodakenetin, exhibited the least cytotoxic capacity against brine shrimp larvae. 相似文献
306.
Hypothermia is not neuroprotective after infection-sensitized neonatal hypoxic–ischemic brain injury
Damjan Osredkar Marianne Thoresen Elke Maes Torun Flatebø Maja Elstad Hemmen Sabir 《Resuscitation》2014
Background
Therapeutic hypothermia (HT) is the standard treatment after perinatal hypoxic–ischemic (HI) injury. Infection increases vulnerability to HI injury, but the effect of HT on lipopolysaccharide (LPS) sensitized HI brain injury is unknown.Design/methods
P7 rat pups were injected either with vehicle or LPS, and after a 4 h delay they were exposed to left carotid ligation followed by global hypoxia inducing a unilateral stroke-like HI injury. Pups were randomized to the following treatments: (1) vehicle treated HI-pups receiving normothermia treatment (NT) (Veh-NT; n = 30); (2) LPS treated HI-pups receiving NT treatment (LPS-NT; n = 35); (3) vehicle treated HI-pups receiving HT treatment (Veh-HT; n = 29); or (4) LPS treated HI-pups receiving HT treatment (LPS-HT; n = 46). Relative area loss of the left/right hemisphere and the areas of hippocampi were measured at P14.Results
Mean brain area loss in the Veh-NT group was 11.2 ± 14%. The brain area loss in LPS-NT pups was 29.8 ± 17%, which was significantly higher than in the Veh-NT group (p = 0.002). The Veh-HT group had a significantly smaller brain area loss (5.4 ± 6%), when compared to Veh-NT group (p = 0.043). The LPS-HT group showed a brain area loss of 32.5 ± 16%, which was significantly higher than in the Veh-HT group (p < 0.001). LPS-HT group also had significantly smaller size of the left hippocampus, which was not found in other groups. LPS-sensitization significantly decreased the sizes of the right, unligated-hemispheres, independent of post-HI treatment.Conclusions
Therapeutic hypothermia is not neuroprotective in this LPS-sensitized unilateral stroke-like HI brain injury model in newborn rats. Lack of neuroprotection was particularly seen in the hippocampus. Pre-insult exposure to LPS also induced brain area loss in the unligated hemisphere, which is normally not affected in this model. 相似文献307.
Allergic rhinitis,rhinoconjunctivitis, and eczema: prevalence and associated factors in children 下载免费PDF全文
Sheetu Singh Bharat Bhushan Sharma Sundeep Salvi Jugesh Chhatwal Kailash Chandra Jain Lata Kumar Mohan Keshav Joshi Suresh Babu Pandramajal Shally Awasthi Sheila Bhave Sylvan Rego Thevaruparambil Unny Sukumaran Vasant A. Khatav Virendra Singh Surendra Kumar Sharma Mohammed Sabir 《The clinical respiratory journal》2018,12(2):547-556
308.
Sarim Rashid MBBS Tayyiba Ahmed Noor MBBS Hamayle Saeed MBBS Asma Sabir Ali MBBS Govinda Meheshwari MBBS Asad Mehmood MBBS Laveeza Fatima MBBS Syed Muhammad Jawad Zaidi MBBS Jahanzeb Malik MBBS Amin Mehmoodi MD Azmat Hayat MBBS MRCP FRCP FHRS 《Annals of noninvasive electrocardiology》2023,28(4):e13059
Objective
Many clinical and preclinical studies have implicated an association between atrial fibrillation (AF) and its progression to imbalances in the gut microbiome composition. The gut microbiome is a diverse and complex ecosystem containing billions of microorganisms that produce biologically active metabolites influencing the host disease development.Methods
For this review, a literature search was conducted using digital databases to systematically identify the studies reporting the association of gut microbiota with AF progression.Results
In a total of 14 studies, 2479 patients were recruited for the final analysis. More than half (n = 8) of the studies reported alterations in alpha diversity in atrial fibrillation. As for the beta diversity, 10 studies showed significant alterations. Almost all studies that assessed gut microbiota alterations reported major taxa associated with atrial fibrillation. Most studies focused on short-chain fatty acids (SCFAs), whereas three studies evaluated TMAO levels in the blood, which is the breakdown product of dietary l -carnitine, choline, and lecithin. Moreover, an independent cohort study assessed the relationship between phenylacetylglutamine (PAGIn) and AF.Conclusion
Intestinal dysbiosis is a modifiable risk factor that might provide newer treatment strategies for AF prevention. Well-designed research and prospective randomized interventional studies are required to target the gut dysbiotic mechanisms and determine the gut dysbiotic-AF relationship. 相似文献309.
Grainne Malone Gerges Abdelsayed Fianait Bligh Fatma Al Qattan Saifullah Syed Prateepan Varatharajullu Augustin Msellati Daniela Mwipatayi Maimoona Azhar Andrew Malone Saulat H. Fatimi Claire Conway Aamir Hameed 《Journal of anatomy》2023,242(1):29-49
Mechanical circulatory support (MCS) devices, such as left ventricular assist devices (LVADs) are very useful in improving outcomes in patients with advanced-stage heart failure. Despite recent advances in LVAD development, pump thrombosis is one of the most severe adverse events caused by LVADs. The contact of blood with artificial materials of LVAD pumps and cannulas triggers the coagulation cascade. Heat spots, for example, produced by mechanical bearings are often subjected to thrombus build-up when low-flow situations impair washout and thus the necessary cooling does not happen. The formation of thrombus in an LVAD may compromise its function, causing a drop in flow and pumping power leading to failure of the LVAD, if left unattended. If a clot becomes dislodged and circulates in the bloodstream, it may disturb the flow or occlude the blood vessels in vital organs and cause internal damage that could be fatal, for example, ischemic stroke. That is why patients with LVADs are on anti-coagulant medication. However, the anti-coagulants can cause a set of issues for the patient—an example of gastrointestinal (GI) bleeding is given in illustration. On account of this, these devices are only used as a last resort in clinical practice. It is, therefore, necessary to develop devices with better mechanics of blood flow, performance and hemocompatibility. This paper discusses the development of LVADs through landmark clinical trials in detail and describes the evolution of device design to reduce the risk of pump thrombosis and achieve better hemocompatibility. Whilst driveline infection, right heart failure and arrhythmias have been recognised as LVAD-related complications, this paper focuses on complications related to pump thrombosis, especially blood coagulopathy in detail and potential strategies to mitigate this complication. Furthermore, it also discusses the LVAD implantation techniques and their anatomical challenges. 相似文献