Biomedical subjects

Yao Li

Publications and source records attributed to Yao Li.

At least 19 recordsLinked to original sources

PubMed2026

Genome-Wide Association Analysis for Growth-Related Traits in Indoor- and Outdoor-Cultured Juvenile Grass Carp (Ctenopharyngodon idella).

Grass carp is a key herbivorous freshwater fish, yet long-term inbreeding reduces growth rates. Current genome-wide association studies (GWAS) primarily focus on a limited range of growth traits, while intestinal morphology is likely to emerge as a promising new proxy for both growth performance and health status. We reared juvenile grass carp from one batch in indoor vs. natural aquatic vegetation groups for 100 days, measuring body weight (BW), length (BL), height (BH), and intestinal length (IL) in 200 individuals (100/group). Phenotypic differences were significant for all traits, with IL most variable. GWAS identified 95 significant SNPs, among which 21 were related to multiple traits. Candidate gene and KEGG pathway analyses linked these SNPs to myogenesis, skeletal development, immunity, calcium signaling, and stress resistance. Twelve SNPs were found to be associated with IL, including 8 multi-trait-related and 4 trait-specific ones. This suggests that IL can serve as a supplementary growth trait. There was no overlap with prior GWAS, but recurrent signals on chromosomes 1, 2, 14 (BW) and 2, 3, 14, 24 (BH) merit further study. Our findings enrich molecular resources for grass carp and highlight IL's potential for marker-assisted breeding.

Ctenopharyngodon idella↗

PubMed2025

A choanoflagellate cGLR-STING pathway reveals evolutionary links between bacterial and animal immunity.

Animal innate immunity evolved from ancient pathways in bacterial anti-phage defense. How bacterial immune components were first acquired and adapted within eukaryotic cells remains poorly understood. Here we identify a complete cGLR-STING signaling axis in choanoflagellates, the closest living relatives of animals, that exhibits a mosaic of features from both bacterial and animal immunity. Comparative genomics reveals choanoflagellate cGLR and STING genes organized in operon-like arrangements reminiscent of bacterial defense loci. Reconstitution of choanoflagellate cGLR-STING signaling in vitro demonstrates that activation occurs through the conserved nucleotide immune signal 2'3'-cGAMP. Structural analysis of a choanoflagellate STING-2'3'-cGAMP complex explains how retention of bacterial-like features in early eukaryotic proteins shapes ligand specificity and receptor activation. We analyze cGLR and STING evolution in unicellular eukaryotes and identify further STING homologs in choanoflagellates and fungi that support additional independent acquisition events. Our results reveal molecular fossils that bridge bacterial and animal immunity and illuminate early eukaryotic immune system evolution.

Journal Article↗

PubMed2007

Hepatic differentiation and transcriptional profile of the mouse liver epithelial progenitor cells (LEPCs) under the induction of sodium butyrate.

The liver regenerates by progenitor cells when it is damaged in chronic liver diseases and extensive damage. The progenitor cells, also termed "oval cells" according to their morphological traits, can differentiate into hepatocytes and bile duct cells in vivo. To better understand the transcriptional pattern that accompanies the hepatic differentiation of oval cells, we applied cDNA microarray to analyze the oval cell-derived liver epithelial progenitor cells (LEPCs) during in vitro induced differentiation. Upon exposure to sodium butyrate, a histone deacetylase inhibitor, cultured LEPCs differentiate and express functional hepatocyte markers albumin, tryptophan 2, 3-dioxygenase and alcohol dehydrogenase. For expression profiling, cells were harvested at 6 h, 12 h, 1 d, 3 d and 7 d after exposure to sodium butyrate. After analyzing the microarray data by SOM clustering, total of 796 differentially regulated genes were grouped into 48 clusters. Consistent with the phenotype change of LEPCs after sodium butyrate treatment, many hepatocyte functional genes are revealed by analyzing the clusters containing genes up-regulated through all the time points. The clusters, containing down-regulated genes immediately after the induction, are also analyzed. The microarray data was validated by analyzing the expression of selected genes by quantitative real-time PCR. A set of genes expressed synergistically in these clusters may play a central role during the process of differentiation. Sodium butyrate decreases cyclin B1 and Cdk4 expression, which would be associated with LEPCs growth arrest shortly after treatment. Bmi1, a polycomb group protein, is also down-regulated immediately after treatment and remains at a low level during the induction. These findings highlight the key molecular mechanisms by which sodium butyrate, mediates its effects on cell growth arrest and induction of differentiation. In conclusion, our data reflect a global view of gene expression during hepatic differentiation of LEPCs induced by sodium butyrate.

Animals↗

PubMed2006

Different roles of MTHFR C677T and A1298C polymorphisms in colorectal adenoma and colorectal cancer: a meta-analysis.

Association studies on the MTHFR polymorphisms (C677T and A1298C) in colorectal cancer (CRC) and colorectal adenoma have shown conflicting results. We performed a meta-analysis to better assess the purported associations. Overall, the 677T allele (10,131 patients and 15,362 controls) showed a small but significant protective effect against CRC compared to the 677C allele [P=0.0003, odds ratio (OR)=0.93; 95% confidence interval (CI) 0.89-0.98, P=0.22 (for heterogeneity)] for a worldwide population. Meta-analyses of other genetic contrasts suggested that the 677T allele is more likely to affect CRC in a recessive genetic model worldwide (P<0.0001, OR=0.86; 95% CI 0.76-0.96, P=0.06) and in Asians (P=0.0005, OR=0.75; 95% CI 0.64-0.88, P=0.71). Similarly, we found a significantly decreased risk of CRC for 1298C polymorphism (4,764 CRC patients and 6,592 controls) for a recessive genetic model worldwide (P=0.005, OR=0.81; 95% CI 0.70-0.94, P=0.40) and in Caucasians (P=0.04, OR=0.75 95% CI 0.57-0.99, P=0.35). No evidence of association of C677T (4,616 patients and 6,338 controls) and A1298C (1,272 patients and 1,684 controls) with colorectal adenoma were found. The evidence accumulated suggests that MTHFR may represent a low-penetrance susceptible gene for CRC, and that the two polymorphisms might protect against colorectal adenoma developing into cancer. A larger single study is required to further evaluate gene-gene and gene-environment interactions for MTHFR polymorphisms and the cancer risk in a specific population.

Adenoma↗

PubMed2006

A novel full-length gene of human ribosomal protein L14.22 related to human glioma.

BACKGROUND: This study was undertaken to obtain differentially expressed genes related to human glioma by cDNA microarray and the characterization of a novel full-length gene. METHODS: Total RNA was extracted form human glioma and normal brain tissue, and mRNA was used as a probe. The results of hybridization procedure were scanned with the computer system. The gene named 507E08 cone was subsequently analyzed by northern blot, bioinformatic approach, and protein expression. RESULTS: Fifteen differentially expressed genes were obtained from human glioma by hybridization and scanning for four times. Northern blot analysis confirmed that the 507E08 clone was low expressed in human brain tissue and over expressed in human glioma tissues. The analysis of BLASTn and BLASTx showed that the 507E08 clone was a novel full-length gene, which codes 203 amino acid of protein and is called human ribosomal protein 14.22 gene. The nucleotide sequence had been submitted to the GenBank with the accession number of AF329277. After expression in E. coli., protein yielded a major band of apparent molecular mass 22 kDa on an SDS-PAGE gel. CONCLUSIONS: cDNA microarray technology can be successfully used to identify differentially expressed genes. The novel full-length gene of human ribosomal protein 13.22 may be correlated with the development of human glioma.

Amino Acid Sequence↗

PubMed2006

SNP genotyping by multiplex amplification and microarrays assay for forensic application.

OBJECTIVE: Research on the application feasibility of SNP genotyping for forensic identification by microarrays. METHODS: Oligonucleotide microarrays which could detect 34 different SNPs were used. After hybridization and washing, the arrays were scanned and fluorescence intensities analyzed using Microarray software. Population studies on 34 SNP loci were carried out in a sample of 109 unrelated Chinese Han individuals using oligonucleotide microarrays for genotype detection. The method was also applied to cases. RESULTS: According to the results of population studies, no deviations from Hardy-Weinberg equilibrium could be found. Among the 34 loci, 3 SNPs were low informative, 4 were medium informative and 27 were high informative. The combination discrimination power (CDP) of the 31 optimal polymorphic SNPs was 0.9999999999979. The matching probability was 2.13 x 10(-12). The average exclusion probability in paternity testing for duos was 0.9609. The average exclusion probability in paternity testing for trios was 0.9970. CONCLUSION: The data and case application demonstrated that SNP typing by oligonucleotide probe microarrays was a useful technique for paternity testing and individual identification. Combined with the 28 SNPs loci distributed on HLA-DRB1 and ABO genes, the combination discrimination power (CDP) was 0.9999999999999910. The matching probability was 9.02 x 10(-15). The average exclusion probabilities in duos and in trios were 0.9894 and 0.9992, respectively. It may be concluded that the 59 SNPs loci yield the same power in forensic identification as CODIS STRs currently used.

China↗

PubMed2006

Application of HLA-DRB1 genotyping by oligonucleotide micro-array technology in forensic medicine.

UNLABELLED: The human leukocyte antigen (HLA) system is known to be the most complex polymorphic system in the human genome. Among all of the HLA loci, HLA-DRB1 has the second largest number of alleles. The purpose of this study is to develop an oligonucleotide micro-array based HLA-DRB1 typing system for use in forensic identification, anthropology, tissue transplantation, and other genetic research fields. The system was developed by analyzing the HLA-DRB1 (DRB1) genotypes in 1198 unrelated healthy Chinese Han individuals originating from various parts of China and residing in Shanghai, China. METHOD: Polymerase chain reaction (PCR) coupled with the oligonucleotide micro-array technology was used to detect and type HLA-DRB1 alleles of the sample individuals. The reliability, sensitivity, consistency and specificity were evaluated for use in forensic identification. Furthermore, a meta-analysis was carried out by comparing the allele frequencies of the HLA-DRB1 locus with those of other Chinese Han groups, Chinese minorities and other ethnic populations. RESULTS: All the DNA samples yielded a 273 bp amplification product, with no other amplification products in this length range. The minimum quantity of DNA detected by this method is 15 ng in a PCR reaction system of 25 microl. The population studied appeared to be not in Hardy-Weinberg equilibrium. Observed heterozygosity (Ho), expected heterozygosity (He), expected probability of exclusion (PE), polymorphic information content (PIC), and discrimination power (DP) of the HLA-DRB1 locus from the Shanghai Han ethnic group were evaluated to be 0.8022, 0.8870, 0.7741, 0.8771, 0.9750, respectively. A total of 25 HLA-DRB1 alleles were identified. HLA-DRB1*09XX, *04XX, *12XX and *15XX were the most frequent DRB1 alleles, which were observed in 58.76% of the sample. One hundred and sixteen genotypes were found. The five most frequent genotypes were: *04XX/*04XX (0.0626), *09XX/*09XX (0.0593), *04XX/*09XX (0.0551), *09XX/*15XX (0.0384) and *08XX/*12XX (0.0351). The meta-analysis showed that there were uniquely distributed features of DRB1 alleles among various ethnic populations and among the studied population groups from various regions with the same ethnic origin. CONCLUSIONS: An HLA-DRB1 genotyping system has been developed and established based on the oligonucleotide micro-array technology. The HLA-DRB1 typing of the Han population in Shanghai has revealed a relatively high heterogeneity. Information obtained in this study will be useful for medical and forensic applications as well as in anthropology research. Large-scale micro-array detection is highly accurate and reliable for DNA-based HLA-DRB1 genotyping. These results suggest that HLA-DRB1 DNA polymorphisms and the database of the Shanghai Han group have useful applications in processing forensic casework (as personal identification, paternity test), tracing population migration and genetic diagnosis.

Animals↗

PubMed2006

DNA repair gene XRCC3 polymorphisms and cancer risk: a meta-analysis of 48 case-control studies.

The X-ray repair cross-complementing group 3 (XRCC3) is a highly suspected candidate gene for cancer susceptibility. However, association studies on the XRCC3 polymorphisms (4541A>G, Thr(241)Met, 17893A>G) in cancer have shown conflicting results. Therefore, we performed a meta-analysis to better assess the purported associations. Forty eight eligible case-control studies including 24,975 cancer patients and 34, 209 controls were selected for our meta-analysis. Overall, individuals carrying the XRCC3 Met/Met genotype showed a small cancer risk under a recessive genetic model. The subgroup and meta-regression analysis demonstrated different scenarios concerning the XRCC3 Met/Met genotype's role in cancer susceptibility for different subgroups. Specially, there was a significantly increased risk of breast cancer (OR, 1.14; P=0.0004; 95% CI, 1.06-1.23; P=0.37 for heterogeneity), elevated but not significant risk of cancer for head and neck, bladder, surprisingly, a significantly decreased risk of non-melanoma skin cancer (OR, 0.76; P=0.007; 95% CI, 0.62-0.93; P=0.61 for heterogeneity). A significantly elevated risk of cancer was observed in population-based case-control studies but not in nested or hospital based studies. Similarly, we found a significantly increased risk of cancer for A4541G and a decreased risk for A17893G under dominant genetic models. Our meta-analysis results support that the XRCC3 might represent a low-penetrance susceptible gene especially for cancer of breast, bladder, head and neck, and non-melanoma skin cancer. A single larger study should be required to further evaluate gene-gene and gene-environment interactions on XRCC3 polymorphisms and tissue-specific cancer risk in an ethnicity specific population.

Amino Acid Substitution↗

PubMed2006

CTLA4 polymorphisms and ophthalmopathy in Graves' disease patients: association study and meta-analysis.

Studies in the past have clearly established that cytotoxic T-lymphocyte antigen-4 (CTLA4) is a susceptible gene for Graves' disease (GD). However, association studies between the CTLA4 exon-1 +49A/G polymorphism and the risk of developing Graves' ophthalmopathy (GO) in GD patients have revealed conflicting results. In this study, associations of two CTLA4 polymorphisms (+49A/G and CT60) with GD risk and GO susceptibility in GD patients were investigated in a Chinese population. In addition, a meta-analysis was performed to better assess the purported association between the +49A/G polymorphism and GO susceptibility in GD patients. Our results demonstrated that both the +49A/G and CT60 polymorphisms were associated with GD susceptibility in the Chinese population. No significant association with GO susceptibility in GD patients was confirmed regardless of which polymorphism was tested individually. Similarly, the meta-analysis results provided minimal evidence about the role of the +49A/G polymorphism and GO risk in GD patients. Interestingly, haplotypic analysis demonstrated different scenarios concerning the role of CTLA4 in GO susceptibility in the Chinese GD patients. We found that the +49A-CT60G haplotype was marginally statistically associated with the increased risk of GO in GD patients (OR = 1.63, 95%CI 1.00-2.64, p = 0.05). In conclusion, our results suggested that CTLA4 might be involved in the susceptibility to GD in the Chinese population. Although neither +49A/G nor CT60 polymorphism was associated with the risk of GO in GD patients, the haplotypic analysis provided some evidence about its role in GO susceptibility in the Chinese GD patients. We suggest that more association studies recruiting haplotypic analysis should be performed to investigate the role of CTLA4 gene in GO susceptibility in patients from different nations.

Adult↗

PubMed2006

A study of conservation genetics in Cupressus chengiana, an endangered endemic of China, using ISSR markers.

ISSR markers were used to analyze the genetic diversity and genetic structure of eight natural populations of Cupressus chengiana in China. ISSR analysis using 10 primers was carried out on 92 different samples. At the species level, 136 polymorphic loci were detected. The percentage of polymorphic bands (PPB) was 99%. Genetic diversity (He) was 0.3120, effective number of alleles (Ae) was 1.5236, and Shannon's information index (I) was 0.4740. At the population level, PPB = 48%, Ae = 1.2774, He = 0.1631, and I = 0.2452. Genetic differentiation (Gst) detected by Nei's genetic diversity analysis suggested 48% occurred among populations. The partitioning of molecular variance by AMOVA analysis indicated significant genetic differentiation within populations (54%) and among populations (46%; P < 0.0003). The average number of individuals exchanged between populations per generation (Nm) was 0.5436. Samples from the same population clustered in the same population-specific cluster, and two groups of Sichuan and Gansu populations were distinguishable. A significantly positive correlation between genetic and geographic distance was detected (r = 0.6701). Human impacts were considered one of the main factors to cause the rarity of C. chengiana, and conservation strategies are suggested based on the genetic characters and field investigation, e.g., protection of wild populations, reestablishment of germplasm bank, and reintroduction of more genetic diversity.

China↗

PubMed2006

LS-CAP: an algorithm for identifying cytogenetic aberrations in hepatocellular carcinoma using microarray data.

Biological techniques such as Array-Comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH) and affymetrix single nucleotide pleomorphism (SNP) array have been used to detect cytogenetic aberrations. However, on genomic scale, these techniques are labor intensive and time consuming. Comparative genomic microarray analysis (CGMA) has been used to identify cytogenetic changes in hepatocellular carcinoma (HCC) using gene expression microarray data. However, CGMA algorithm can not give precise localization of aberrations, fails to identify small cytogenetic changes, and exhibits false negatives and positives. Locally un-weighted smoothing cytogenetic aberrations prediction (LS-CAP) based on local smoothing and binomial distribution can be expected to address these problems. LS-CAP algorithm was built and used on HCC microarray profiles. Eighteen cytogenetic abnormalities were identified, among them 5 were reported previously, and 12 were proven by CGH studies. LS-CAP effectively reduced the false negatives and positives, and precisely located small fragments with cytogenetic aberrations.

Algorithms↗

PubMed2006

Analysis of common gene expression patterns in four human tumor cell lines exposed to camptothecin using cDNA microarray: identification of topoisomerase-mediated DNA damage response pathways.

Camptothecin (CPT) is a potent inhibitor of DNA topoisomerase I with a wide spectrum of anti-tumor activity. Relatively little information is available regarding the relation of known topoisomerase-mediated DNA damage with other intracellular pathways. To gain an insight into the intracellular molecular mechanisms of Topoisomerase I inhibitor camptothecin-mediated DNA damage leading to cell death, we used a high-density cDNA microarray to assess sensitive early gene expression profiles in SGC7901 (gastric cancer), Hela (cervical adenocarcinoma), K562 (chronic myelogenous leukemia) and HL60 (promyelocytic leukemia) tumor cells stimulated with camptothecin for 1 h at the concentrations of GI50 (50 % growth inhibition after 24 h of treatment). Analysis of the differentially expressed genes obtained 29 response genes common to all four cell lines. Moreover, these cell lines also shared the direction of regulation. Most of these common response genes were functionally related to cell proliferation or apoptosis, and some of them were involved in ATM (ataxia-telangiectasia mutated) and ATR (ATM-and Rad3 related) checkpoint pathways, JNK (c-Jun N-terminal kinase) pathway, the survival phosphatidylinositol (PI) 3 kinase-Akt-dependent pathway, mitochondrial cell death pathway, endoplasmic reticulum (ER)-related cell death pathway, and to ubiquitin/proteasome dependent protein degradation pathway. The data provides evidence for a linkage between topoisomerase-mediated DNA damage and intracellular signaling events, which may facilitate our understanding of the camptothecin mediated molecular mechanisms of action.

Antineoplastic Agents, Phytogenic↗

PubMed2006

Screening genetically modified organisms using multiplex-PCR coupled with oligonucleotide microarray.

In this research, we developed a multiplex polymerase chain reaction (multiplex-PCR) coupled with a DNA microarray system simultaneously aiming at many targets in a consecutive reaction to detect a genetically modified organism (GMO). There are a total of 20 probes for detecting a GMO in a DNA microarray which can be classified into three categories according to their purpose: the first for screening GMO from un-transgenic plants based on the common elements such as promoter, reporter and terminator genes; the second for specific gene confirmation based on the target gene sequences such as herbicide-resistance or insect-resistance genes; the third for species-specific genes which the sequences are unique for different plant species. To ensure the reliability of this method, different kinds of positive and negative controls were used in DNA microarray. Commercial GM soybean, maize, rapeseed and cotton were identified by means of this method and further confirmed by PCR analysis and sequencing. The results indicate that this method discriminates between the GMOs very quickly and in a cost-saving and more time efficient way. It can detect more than 95% of currently commercial GMO plants and the limits of detection are 0.5% for soybean and 1% for maize. This method is proved to be a new method for routine analysis of GMOs.

Animals↗

PubMed2006

Adenosine regulation of cystic fibrosis transmembrane conductance regulator through prostenoids in airway epithelia.

Cystic fibrosis is caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, leading to altered ion transport, chronic infection, and excessive inflammation. Here we investigated regulation of CFTR in airway cell monolayers by adenosine, adenosine receptors, and arachidonic acid. Our studies demonstrate that the A2B adenosine receptor is expressed at high levels relative to the other adenosine receptor subtypes, with a characteristic low-affinity profile for adenosine-stimulated CFTR Cl- currents in both Calu-3 cells and CFBE41o- airway cell monolayers stably transduced with wild-type CFTR. The levels of adenosine found in sputum from patients with cystic fibrosis with moderate to severe lung disease stimulated apical prostaglandin release in Calu-3 and CFBE41o- cells, implicating adenosine regulation of phospholipase A2 (PLA2) activity. A2B adenosine receptor and arachidonic acid stimulation produced CFTR-dependent currents in airway monolayers and increased cAMP levels that were sensitive to cyclooxygenase inhibition. Arachidonic acid demonstrated dual regulation of CFTR, stimulating CFTR and Cl- currents in intact airway monolayers, and potently inhibiting PKA-activated Cl- currents in excised membrane patches. Cl- currents produced by arachidonic acid were sensitive to inhibition of PKA, cyclooxygenase, and 5-lipoxygenase. Together, the results provide a converging mechanism to link regulation of CFTR and airway cell inflammation through adenosine and adenosine receptors.

Adenosine↗

PubMed2006

Genes differentially expressed in responsive and refractory acute leukemia.

DNA microarray in 22 patients with acute leukemia revealed genes which were differentially expressed. Ribosomal protein SA (RPSA), minichromosome maintenance deficient 2 (MCM2) and heterogeneous nuclear ribonucleoprotein A1 (HNRPA1) were significantly upregulated (p<0.05, t test) in refractory patients, suggesting that they may play a role in refractoriness in acute leukemia and could be biomarkers of prognosis.

Adolescent↗

PubMed2006

Effectiveness of an HIV/AIDS educational programme for Chinese nurses.

AIM: This paper reports a study examining the effect of a multifaceted HIV/AIDS educational intervention on the knowledge, attitudes and willingness of Chinese nurses in caring for patients with human immunodeficiency virus. BACKGROUND: The expanding HIV/AIDS epidemic challenges nurses to increase their knowledge about this devastating illness to provide effective HIV/AIDS prevention and care to their patients. HIV/AIDS educational interventions, which were developed for North American and European nurses, have not been studied among nurses in other societies. METHODS: The study employed a pretest, post-test experimental design with 208 nurses from seven Chinese provinces. The intervention consisted of a 5-day workshop comprising didactic lectures interspersed with activities designed to elicit discussion of participants' values and personal feelings about HIV/AIDS. Bloom's Taxonomy and principles of good HIV/AIDS educational practice guided the educational intervention. Outcome variables were HIV/AIDS knowledge, attitude toward patients with HIV/AIDS (including empathy for and desire to avoid these patients) and willingness to provide nursing care to these patients. The data were collected in 2003. FINDINGS: At baseline, HIV/AIDS knowledge was not high and attitudes and willingness to care were neutral. Knowledge, attitudes toward patients with HIV/AIDS and willingness to provide nursing care to these patients were each improved at the conclusion of the workshop (P<0.001). CONCLUSIONS: As the HIV/AIDS epidemic expands, nurses will be called upon to deliver competent, compassionate and comprehensive care to patients and their significant others. Intensive, interactive HIV/AIDS professional workshops can contribute to the national effort by increasing knowledge and improving attitudes towards and willingness to provide nursing care for patients with HIV/AIDS.

China↗

PubMed2006

Impaired dynamic cerebral autoregulation in middle cerebral artery stenosis.

BACKGROUND AND PURPOSE: Analysis of dynamic cerebral autoregulation during transient falls in blood pressure is considered a sensitive and convenient method for evaluating patients with carotid artery stenosis. To this point, there have been few reports on the efficacy of using the thigh cuffs technique to analyse middle cerebral artery (MCA) stenosis. If it could be determined whether cerebral blood flow can be maintained (autoregulated) during sudden falls in arterial blood pressure (ABP), then it might be possible to identify patients with MCA stenosis who are at risk of stroke. METHODS: We used the thigh cuff technique to estimate dynamic cerebral autoregulation in 57 patients with MCA stenosis and 72 normal controls. After a stepwise fall in arterial blood pressure, we determined the rate of the rise of MCA blood velocity and compared it with the rate of the rise of arterial blood pressure. In this manner, the dynamic cerebral autoregulation of 11 patients undergoing MCA M1 stent angioplasty was estimated both pre- and post-operation. RESULTS: The autoregulatory index (ARI) was significantly reduced in patients with stenosed/occluded MCA (3.24 +/- 1.52), as compared with normal controls (5.25 +/- 1.39; p<0.001) (results reported as mean +/- SD). Poor ARI values are usually observed in patients with a higher degree of stenosis and particularly in patients with insufficient collateral compensation. ARI was significantly reduced in severe stroke patients (modified ranking scale>or=1), as compared with asymptomatic or TIA patients (p<0.05). After MCA stent angioplasty was performed, there was a significant improvement in ARI in 11 subjects, which caused a mean increase in ARI from 2.08 +/- 1.10 to 3.80 +/- 1.36 (p=0.008). CONCLUSIONS: Dynamic cerebral autoregulation is impaired in patients with middle cerebral artery stenosis. Assessing dynamic cerebral autoregulation may allow a subgroup of patients with MCA stenosis who are at risk of hemodynamic stroke to be identified. Dynamic cerebral disautoregulation in patients with severe MCA stenosis is mostly remedied by stent angioplasty.

Adult↗

PubMed2005

Mutations in the amino terminus of the cystic fibrosis transmembrane conductance regulator enhance endocytosis.

Efficient endocytosis of the cystic fibrosis transmembrane conductance regulator (CFTR) is mediated by a tyrosine-based internalization signal in the CFTR carboxyl-terminal tail 1424YDSI1427. In the present studies, two naturally occurring cystic fibrosis mutations in the amino terminus of CFTR, R31C, and R31L were examined. To determine the defect that these mutations cause, the Arg-31 mutants were expressed in COS-7 cells and their biogenesis and trafficking to the cell surface tested in metabolic pulse-chase and surface biotinylation assays, respectively. The results indicated that both Arg-31 mutants were processed to band C at approximately 50% the efficiency of the wild-type protein. However, once processed and delivered to the cell surface, their half-lives were the same as wild-type protein. Interestingly, indirect immunofluorescence and cell surface biotinylation indicated that the surface pool was much smaller than could be accounted for based on the biogenesis defect alone. Therefore, the Arg-31 mutants were tested in internalization assays and found to be internalized at 2x the rate of the wild-type protein. Patch clamp and 6-methoxy-N-(3-sulfopropyl)quinolinium analysis confirmed reduced amounts of functional Arg-31 channels at the cell surface. Together, the results suggest that both R31C and R31L mutations compromise biogenesis and enhance internalization of CFTR. These two additive effects contribute to the loss of surface expression and the associated defect in chloride conductance that is consistent with a disease phenotype.

Animals↗