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Biomedical subjects

J Lin

Publications and source records attributed to J Lin.

At least 55 records · Page 3Linked to original sources

Evidence of an association between genetic variation of the coactivator PGC-1beta and obesity.

BACKGROUND: Peroxisome proliferator activated receptor-gamma coactivator-1beta (PGC-1beta) is a recently identified homologue of the tissue specific coactivator PGC-1alpha, a coactivator of transcription factors such as the peroxisome proliferators activated receptors and nuclear respiratory factors. PGC-1alpha is involved in adipogenesis, mitochondrial biogenesis, fatty acid beta oxidation, and hepatic gluconeogenesis. METHODS: We studied variation in the coding region of human PPARGC1B in Danish whites and related these variations to the prevalence of obesity and type 2 diabetes in population based samples. RESULTS: Twenty nucleotide variants were identified. In a study of 525 glucose tolerant subjects, the Ala203Pro and Val279Ile variants were in almost complete linkage disequilibrium (R2 = 0.958). In a case-control study of obesity involving a total of 7790 subjects, the 203Pro allele was significantly less frequent among obese participants (p = 0.004; minor allele frequencies: normal weight subjects 8.1% (95% confidence interval: 7.5 to 8.8), overweight subjects 7.6% (7.0 to 8.3), obese subjects 6.5% (5.6 to 7.3)). In a case-control study involving 1433 patients with type 2 diabetes and 4935 glucose tolerant control subjects, none of the examined variants were associated with type 2 diabetes. CONCLUSIONS: Variation of PGC-1beta may contribute to the pathogenesis of obesity, with a widespread Ala203 allele being a risk factor for the development of this common disorder.

Aged↗

Recessive mutations in the CYP4V2 gene in East Asian and Middle Eastern patients with Bietti crystalline corneoretinal dystrophy.

BACKGROUND: Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessively inherited disorder characterised by tiny yellowish glittering retinal crystals, choroidal sclerosis, and crystals in the peripheral cornea, associated with progressive night blindness. CYP4V2, encoding a member of cytochrome p450 (CYP450) protein family, was recently identified as the causative gene. METHODS: We recruited 11 unrelated patients with BCD and characteristic clinical features; eight of Japanese, two of Middle Eastern, and one of Chinese ancestry. Genomic DNA was extracted from peripheral blood leucocytes, and all 11 exons and the flanking intron splice sites of the CYP4V2 gene were amplified and sequenced. A complete ophthalmological examination was performed. RESULTS: We found recessive mutations in the CYP4V2 gene in all of the 11 patients. Two novel mutations, L173W and Q450X, were identified in a Japanese patient and two unrelated patients from Middle Eastern countries, respectively. Each patient was a homozygote. A previously reported mutation IVS6-8_810delinsGC was identified in seven unrelated Japanese patients and the Chinese patient with BCD. All patients with BCD shared a characteristic fundus appearance with numerous intraretinal crystal deposits and atrophy of the retinal pigment epithelium. However, the clinical findings, including elecroretinograph recordings, indicated that there was considerable variation in the degree of visual dysfunction even among patients of similar ages carrying the same mutation. CONCLUSIONS: Defects in CYP4V2 are the main cause of BCD. The IVS6-8_810delinsGC mutant allele may be especially prevalent among patients with BCD in East Asian countries, resulting from a single founder. Variation of disease severity suggests that environmental or additional genetic factors influence the course of the retinal disease.

Adult↗

Highly ordered carbon nanotubes based on porous aluminum oxide: fabrication and mechanism.

Highly ordered carbon nanotubes (CNTs) are wildly pursued due to their unique properties. Anodic aluminum oxide (AAO) exhibits great possibility for this purpose. Here, CNTs based on AAO template were produced using acetylene or ethylene as the hydrocarbon sources with or without the presence of Co catalysts. CNTs grown on the Co-embedded AAO samples were normally confined within the nanopores of the AAO template. It was found that C2H4 normally requires 100 degrees C higher pyrolysis temperature than C2H2 under otherwise identical conditions. The pyrolysis temperature is greatly reduced with the presence of Co catalysts. CNTs can grow out of the nanopores, if Co particles are present at the bottom of the nanopores and if the nanopores are short in length or large in diameter. The graphitization of AAO template grown CNTs was studied by Raman spectroscopy. The CNTs produced from ethylene are generally better in graphitization than those from acetylene, and the CNTs grown with the presence of Co catalysts deposited at the bottom of nanopores are better than those without Co catalysts or with Co catalysts coated on the entire inner wall of nanopores. The growth temperature is found not to play a critical role in graphitization.

Aluminum Oxide↗

Metal oxide coating on carbon nanotubes by a methanol-thermal method.

A methanol-thermal method has been developed to fabricate one-dimensional composite nanowires by coating multiwalled carbon nanotubes with lanthanum oxide and iron oxide, respectively. The coating structure and composition have been investigated by transmission electron microscopy and the X-ray energy dispersive spectrum. Magnetic measurement for the iron oxide coatings indicated that the coercivity has been enhanced after coating. The method reported here provides a novel procedure for the fabrication of one-dimensional composite nanostructures.

Crystallization↗

Information theory in prediction of cleavage sites of signal peptides.

Information theory is used to analyze the character of signal peptide quantitatively, especially residents. On the basis of the above analysis, a method named simplified information-matrix has been developed to predict the cleavage sites of signal peptides. A comparison between the results of weight-matrix and simplified information-matrix is presented.

Computational Biology↗

Combining laparoscopic and endovascular techniques to improve the outcome of aortic endografts. Hybrid techniques.

Aortic endografting can be performed with a high initial success rate yet with the need for lifelong surveillance because of numerous long term problems. Among these graft migration, typ II endoleaks and endotension require treatment to prevent abdominal aortic aneurysm (AAA) rupture. We describe our experience with laparoscopic clipping of lumbar arteries and the inferior mesenteric artery (IMA) to prevent Type II leaks as well as with different banding procedures. Several ways to perform active graft fixation are described. Since we believe that active downsizing of the aneurysm reduces some of the intermediate term problems we go a step further and evacuate the thrombus to downsize the aneurysm to prevent longitudinal shrinkage. Laparoscopic techniques can also be used to obtain direct vascular access. This permits insertion of a thoracic endograft directly into the aorta in patients with diseased iliac vessels. Endovascular aneurysm repair (EVAR) insertion under laparoscopic navigation without contrast dye in cases with renal insufficiency is described. We describe our technique of total laparoscopic conversion after failed endografting. Future perspectives and preliminary experience with an aortic stapler are discussed.

Aged↗

Inhibition of AKT survival pathway by a small molecule inhibitor in human endometrial cancer cells.

The PTEN (phosphatase and tensin homolog deleted on chromosome 10) tumour suppressor is mutated in 40-50% of human endometrial cancers. PTEN exerts its effects in part via inhibition of the antiapoptotic protein AKT. We demonstrate that two endometrial cancer cell lines that harbour PTEN mutations, Ishikawa and RL95-2, have high levels of phosphorylated AKT and high AKT kinase activity. Two additional endometrial cancer cell lines that express wild-type PTEN, Hec1A and KLE, have little phosphorylated AKT and minimal demonstrable AKT kinase activity. We tested a potential inhibitor of the AKT pathway, API-59CJ-OMe, in these four cell lines. We found that API-59CJ-OMe inhibits AKT kinase activity and induces apoptosis in the Ishikawa and RL95-2 cell lines with high AKT activity, but has little effect on Hec1A and KLE cells without AKT activity. API-59CJ-OMe may therefore have therapeutic potential for those endometrial cancers that harbour PTEN mutations and AKT activation.

Apoptosis↗

Role of data aggregation in biosurveillance detection strategies with applications from ESSENCE.

INTRODUCTION: Syndromic surveillance systems are used to monitor daily electronic data streams for anomalous counts of features of varying specificity. The monitored quantities might be counts of clinical diagnoses, sales of over-the-counter influenza remedies, school absenteeism among a given age group, and so forth. Basic data-aggregation decisions for these systems include determining which records to count and how to group them in space and time. OBJECTIVES: This paper discusses the application of spatial and temporal data-aggregation strategies for multiple data streams to alerting algorithms appropriate to the surveillance region and public health threat of interest. Such a strategy was applied and evaluated for a complex, authentic, multisource, multiregion environment, including >2 years of data records from a system-evaluation exercise for the Defense Advanced Research Project Agency (DARPA). METHODS: Multivariate and multiple univariate statistical process control methods were adapted and applied to the DARPA data collection. Comparative parametric analyses based on temporal aggregation were used to optimize the performance of these algorithms for timely detection of a set of outbreaks identified in the data by a team of epidemiologists. RESULTS: The sensitivity and timeliness of the most promising detection methods were tested at empirically calculated thresholds corresponding to multiple practical false-alert rates. Even at the strictest false-alert rate, all but one of the outbreaks were detected by the best method, and the best methods achieved a 1-day median time before alert over the set of test outbreaks. CONCLUSIONS: These results indicate that a biosurveillance system can provide a substantial alerting-timeliness advantage over traditional public health monitoring for certain outbreaks. Comparative analyses of individual algorithm results indicate further achievable improvement in sensitivity and specificity.

Algorithms↗

A modified p53 enhances apoptosis in sarcoma cell lines mediated by doxorubicin.

Mdm2 is frequently overexpressed in sarcoma cells and may contribute to drug resistance by increasing p53 degradation. We investigated the induction of apoptosis in sarcoma cells via adenovirus-mediated gene transfer of wild-type p53 and two modified p53 genes, p53 14/19 and p53 22/23, whose protein products are resistant to Mdm2-mediated degradation. We found that adenovirus-wt p53 (Ad-wt p53) induces significant apoptosis in HT1080 fibrosarcoma cells expressing low levels of Mdm2, but fails to induce apoptosis in SJSA osteosarcoma cells expressing high levels of Mdm2. In contrast, Ad-p53 14/19 induces significant apoptosis in both cell lines. Interestingly, Ad-p53 22/23, a vector encoding a transcription-defective p53 mutant, causes limited apoptosis in both cell lines. We demonstrate that doxorubicin induces phosphorylation of both wt p53 and p53 14/19 protein at multiple sites. We tested the efficacy of doxorubicin and cisplatin with either Ad-wt p53, Ad-p53 22/23 or Ad-p53 14/19. SJSA cells, although harbouring endogenous wt p53, did not undergo significant apoptosis following doxorubicin or cisplatin exposure alone or combined with Ad-wt p53. In contrast, doxorubicin or cisplatin plus Ad-p53 14/19 induced significant apoptosis. Gene transfer of p53 14/19 in combination with the administration of doxorubicin or cisplatin is a potential therapeutic approach for cancers expressing high levels of Mdm2.

Adenoviridae↗

Ventral brainstem enterogenous cyst: an unusual location.

Enterogenous cysts mostly locate in the spinal canal and have only rarely been reported in an intracranial site. We report a case of enterogenous cyst in the ventral to brainstem. The 45-year-old woman presented with paroxysmal headache and diplopia. A CT scan and MRI revealed a cystic clival mass from midbrain to medulla. Subtotal resection was performed using a sub-temporal approach and the patient made a good recovery. Pathological examination revealed that the lesion was a typical enterogenous cyst.

Brain Diseases↗

Genetic diversity and virulence gene determinants of antibiotic-resistant Salmonella isolated from preharvest turkey production sources.

This study evaluated the molecular diversity of 29 Salmonella serotypes isolated from turkey ceca and the production environment. Isolates were resistant to bacitracin (100%), erythromycin (100%), novobiocin (100%), rifampin (100%), streptomycin (62%), gentamicin (52%), spectinomycin (48%), tetracycline (31%), sulfamethoxazole/trimethoprim (SXT) (3%) and tobramycin (3%). The minimum inhibitory concentration (MIC) values ranged from 32 to >/=1024 microg/ml. The pulsed-field gel electrophoresis (PFGE) and ribotyping patterns were identical within each of the serotypes Heidelberg, Worthington and Muenster. The plasmid profiles were identical within each of the Salmonella serotypes. Two different clones of Salmonella anatum were differentiated by PFGE typing but not by ribotyping. Heidelberg isolates from nine turkey ceca and three drinker samples had identical antibiotic resistance, PFGE, ribotype and plasmid patterns, suggesting that transmission of this particular clone may have occurred between the birds and the drinkers. Identical PFGE, ribotype and plasmid patterns were observed in one Salmonella worthington isolate from turkey ceca in one flock and two S. worthington isolates from feeder contents and drinkers from a subsequent flock, suggesting transmission of this pathogen between flocks. Individual and multiple polymerase chain reaction (PCR) analyses revealed the presence of the virulence genes invA, aceK and sopB and the absence of the h-1i gene in all isolates. A combination of genotypic and phenotypic markers can be useful in studying genetic variation among natural salmonellae populations in turkey production and delineating possible transmission pathways.

Animal Husbandry↗

School bag carriage and pain in school children.

PURPOSE: In South Africa (SA), anecdotal evidence for the incidence of shoulder, back and neck pain in school children is alarming but no scientific studies have confirmed this impression. The purpose of the present study was to determine the relationship between pain and school bag carriage in scholars in Durban, SA. METHOD: A study was carried out at four different schools in the Verulam and Chatsworth Regions in Kwa-Zulu Natal, SA. Schools were selected by convenience. One hundred and seventy six scholars between the ages of 11 and 14 years correctly filled out a questionnaire with open-ended and closed-ended questions. Each child also had his/her body and bag weight measured. RESULTS: In this study, most of the scholars experienced shoulder and a combination of shoulder and other bodily pain. The majority of the children carried backpacks over two shoulders. The type of bag carried was significantly related to pain experienced (0.00). A significantly larger number of female scholars experienced pain. CONCLUSION: The shoulder and other bodily pain experienced by the sample of scholars are strongly related to the type of bag and the gender of the children. More in-depth studies into identifying risk factors for bodily pains in school children are indicated.

Adolescent↗

Too much short chain fatty acids cause neonatal necrotizing enterocolitis.

Nenatal necrotizing enterocolitis (NEC) is a disease mainly affects premature infants. It is well known that prematurity, enteral formula feeding, and bacterial colonization are three major risk factors for NEC. Acetic acid, propionic acid and butyric acid are short chain fatty acids (SCFAs), which are produced mainly in the colon by bacterial fermentation of undigested carbohydrates. Although luminal production of modest quantities of SCFAs is essential for normal colonic mucosal function, excessive production/accumulation of SCFAs may arise in premature infants due to increased luminal carbohydrates malabsorption and poor gastrointestinal motility, and may have deleterious effects on mucosal integrity. Therefore, it is proposed that too much luminal short chain fatty acids cause neonatal NEC.

Animals↗

Evaluation of adipocyte apoptosis by laser scanning cytometry.

OBJECTIVE: Adipocyte apoptosis plays an important role in adipose tissue homeostasis and can be altered under a variety of physiological and pathological conditions. This study was carried out to determine whether laser scanning cytometry (LSC) can be used to measure changes in apoptosis of adipocytes over time. DESIGN: LSC was used to investigate adipocyte apoptosis induced by tumor necrosis factor-alpha (TNF-alpha), a cytokine that is associated with obesity and insulin resistance. LSC, a slide-based solid phase cytofluorometer, provides quantitative flow fluorescence data together with morphological information for apoptotic detection. Both 3T3-L1 cells and rat adipocytes from primary cell culture were incubated with 0 or 25 nM TNF-alpha for up to 24 h. Both the FITC-conjugated annexin V/propidium iodide assay and the TUNEL assay were used to distinguish cells with apoptotic characteristics from nonapoptotic cells. RESULTS: Apoptosis did not increase over time in the absence of TNF-alpha for both 3T3-L1 cells and rat primary adipocytes. For both 3T3-L1 cells and rat primary adipocytes, a significant increase in the percentage of apoptotic cells was observed by 3-4 h incubation with TNF-alpha (P<0.05). By 24 h, more than 50% of cells incubated with TNF-alpha were apoptotic (P<0.001). This process was also associated with morphological changes typical of adipocytes undergoing apoptosis. By estimating the percentage of cell subpopulations after different times of incubation with TNF-alpha, we were able to develop grading parameters, based on the adipose apoptotic measurements. CONCLUSION: With morphological information, LSC can be a useful tool to evaluate adipocyte apoptosis.

Adipocytes↗

Identification of a novel HLA-DPB1 allele--DPB1*0102.

In this report, we describe the identification of a novel HLA-DPB1 allele, DPB1*0102, which was first found in a 27-year-old woman and was later detected again in another person, from the Han population of China. According to the nucleotide alignment, DPB1*0102 was the most similar to DPB1*0202, with only one nucleotide substitution from A to G at position 192 among three closely related alleles--DPB1*0202, DPB1*2401 and DPB1*0501. This substitution was a non-synonymous one, which caused a change of amino acid from E to K at codon 69 of DP beta-chain in the mature protein.

Adult↗