Creutzfeldt-Jakob disease in a Chinese patient with a novel seven extra-repeat insertion in PRNP.
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Adult↗
Biomedical subjects
J Han
Publications and source records attributed to J Han.
Interaction between GNB3 C825T and ACE I/D polymorphisms in essential hypertension in Koreans.
Essential hypertension (EH) is considered a typical polygenic disease, so the evaluation of gene-gene interactions rather than the determination of single gene effects is crucial to understanding any genetic influences. The G-protein beta3-subunit (GNB3) 825T allele, associated with enhanced G-protein signalling, is a strong candidate for interactions with polymorphisms, such as insertion/deletion (I/D) polymorphism of angiotensin I-converting enzyme (ACE) gene. We investigated whether there is an association between GNB3 C825T and ACE I/D polymorphisms for the development of EH. We carried out a case-control study of 688 hypertensive and 924 normotensive subjects recruited from South Korea. The GNB3 C825T and ACE I/D genotypes were determined by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods, respectively. The distributions of alleles and genotypes for the GNB3 C825T and ACE I/D polymorphisms were not found to be significantly associated with hypertensive status in either males or females. Logistic regression analysis indicated that the GNB3 825T allele carriers were positively associated with EH in males (odds ratio (OR) for TT/CT, 1.459; 95% confidence interval (CI), 1.048-2.033, P=0.0255). In analysis of gene-gene interaction, we found that there was a significant interaction between the GNB3 825T and ACE D alleles (P<0.05). OR for EH was significantly higher in 825T allele carriers with ACE D allele (OR, 1.490; 95% CI, 1.117-1.987, P=0.0067). A significant interaction between the GNB3 825T and the ACE D alleles may contribute to the predisposing effect for the development of EH in Koreans.
Adult↗
Lower Cambrian vendobionts from China and early diploblast evolution.
Ediacaran assemblages immediately predate the Cambrian explosion of metazoans and should have played a crucial role in this radiation. Their wider relationships, however, have remained refractory and difficult to integrate with early metazoan phylogeny. Here, we describe a frondlike fossil, Stromatoveris (S. psygmoglena sp. nov.), from the Lower Cambrian Chengjiang Lagerstätte (Yunnan, China) that is strikingly similar to Ediacaran vendobionts. The exquisite preservation reveals closely spaced branches, probably ciliated, that appear to represent precursors of the diagnostic comb rows of ctenophores. Therefore, this finding has important implications for the early evolution of this phylum and related diploblasts, some of which independently evolved a frondose habit.
Animals↗
Endoscopic removal of biliary self-expandable metallic stents: a prospective study.
BACKGROUND AND STUDY AIMS: The transpapillary endoscopic insertion of self-expandable metallic stents (SEMSs) has been widely used for the palliation of unresectable malignant biliary obstruction. We attempted the endoscopic removal of malfunctioning SEMSs. The aim of this study was to assess the feasibility and safety of the endoscopic removal of SEMSs by comparing the results between removal of covered and uncovered SEMSs. PATIENTS AND METHODS: 30 patients with a malfunctioning biliary SEMS prospectively underwent an attempt at endoscopic removal of the biliary SEMS over a 2-year period. Removal of the malfunctioning SEMS was done with a therapeutic duodenoscope (ED-450XT5 or TJF-240), using a rat-tooth forceps. Of the 30 SEMS used, 22 were silicone-covered Wallstents, while eight were uncovered SEMSs including five uncovered Wallstents and three Zilver stents. The time for an attempt at each endoscopic removal was limited to 15 minutes in a single endoscopic procedure session. RESULTS: The covered SEMSs were easily removed in 19 out of 22 patients (86.4 %), whereas none of the eight uncovered SEMSs (0 %) could be removed. The only factor predicting successful stent removal was the presence of a stent covering ( P = 0.000). There was no morbidity or mortality related to endoscopic removal of malfunctioning stents. CONCLUSIONS: In contrast to uncovered biliary SEMSs, in most cases malfunctioning covered biliary SEMSs can be easily and safely removed endoscopically using a rat-tooth forceps.
Aged↗
Physical and microbiological stability of an extemporaneous tacrolimus suspension for paediatric use.
OBJECTIVE: An extemporaneous suspension of tacrolimus for paediatric use has recently been developed but poor bioavailability and erratic plasma concentrations were observed during clinical use. It was not clear whether this was due to changes in the physical properties of the suspension during storage. The aim of this work was to investigate the physical and microbiological stability over the recommended 8-week shelf-life of this extemporaneous tacrolimus suspension. METHODS: Suspensions (0.5 mg/mL) were custom made by a special manufacturer under Good Manufacturing Practice conditions. The procedure involved mixing tacrolimus capsule contents into Ora Plus and Simple Syrup (1 : 1) using a mortar and pestle followed by an homogenization step. The particle sizes of the suspensions were measured using a MasterSizer. A light microscope equipped with polarizers was used to visualize any particle size changes or crystal growth. Viable bacterial and fungal contamination was assessed using standard colony count techniques on solid media. The suspensions were kept at 22-26 degrees C and evaluated weekly. RESULTS: The volume mean diameter d((4,3)) from laser diffraction did not change significantly. Light microscopy did not reveal any significant change in particle size or crystal growth. Contamination by viable and culturable micro-organisms could not be detected. CONCLUSION: The suspension was physically (particle size) and microbiologically stable during the 8-week study period suggesting other factors including poor dosing could be responsible for the pharmacokinetic variation observed during clinical use which warrants further investigation.
Biological Availability↗
Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes.
AIM: Exenatide, an incretin mimetic for the adjunct treatment of type 2 diabetes (DM2), reduced A1C and weight in 30-week placebo-controlled trials. This analysis examined the effects of exenatide on glycaemic control and weight over an 82-week period in patients with DM2 unable to achieve adequate glycaemic control with sulphonylurea (SU) and/or metformin (MET). METHODS: This interim analysis is of 314 patients who received exenatide in the 30-week placebo-controlled trials and subsequently in 52 weeks of open-label uncontrolled extension studies for 82 weeks of exenatide in total. Patients continued their SU and/or MET regimens throughout. RESULTS: Patients completed 82 weeks of exenatide treatment [n = 314, 63% M, age 56 +/- 10 years, weight 99 +/- 21 kg, body mass index 34 +/- 6 kg/m2, A1C 8.3 +/- 1.0% (mean +/- SD)]. Reduction in A1C from baseline to week 30 [-0.9 +/- 0.1% (mean +/- SE)] was sustained to week 82 (-1.1 +/- 0.1%), with 48% of patients achieving A1C < or = 7% at week 82. At week 30, exenatide reduced body weight (a secondary endpoint) from baseline (-2.1 +/- 0.2 kg), with progressive reduction at week 82 (-4.4 +/- 0.3 kg). Similar results were observed for the intent-to-treat population (n = 551), with reductions in A1C and weight at week 82 of -0.8 +/- 0.1% and -3.5 +/- 0.2 kg respectively. The 82-week completer cohort showed statistically significant improvement in some cardiovascular risk factors. The most frequent adverse events were generally mild-to-moderate nausea and hypoglycaemia. CONCLUSION: In summary, 82 weeks of adjunctive exenatide treatment in patients with DM2 treated with SU and/or MET resulted in sustained reduction in A1C and progressive reduction in weight, as well as improvement in some cardiovascular risk factors.
Adolescent↗
Giant fibrovascular polyp of the esophagus: CT findings.
Giant fibrovascular polyp of the esophagus is a rare intraluminal benign tumor that is covered with normal esophageal mucosa, which consists of fibrous tissue, adipose tissue, and vascular structures. We report a case of a giant fibrovascular polyp of the esophagus in which feeding vessels were well visualized within the stalk of the mass at contrast-enhanced helical computed tomography.
Esophageal Neoplasms↗
Expressions of galectin-3, glutathione S-transferase A2 and peroxiredoxin-1 by nonylphenol-incubated Caco-2 cells and reduction in transepithelial electrical resistance by nonylphenol.
Nonylphenol, an estrogenic xenobiotic widely used in the manufacture of plastics and detergents, has been found in drinking water and may therefore enter the body through the oral route. Thus, intestinal cells lining the alimentary tract serve as the body's first line of defense against this compound. In this study, the effects of nonylphenol on the human intestinal cell line Caco-2 were determined using transepithelial electrical resistance (TEER) measurement and proteomics. Results show that 10 microM nonylphenol can disrupt the tight-junction permeability of Caco-2 cells in approximately 15 min. Incubating the cells with 1 or 10 microM nonylphenol for 6 days resulted in the enhanced expressions of galectin-3 (approximately 4-fold vs. control with 1 microM; 2-fold with 10 microM), glutathione S-transferase A2 (approximately 8-fold with 1 microM; 5-fold with 10 microM) and peroxiredoxin-1 (approximately 6-fold with 1 microM; 4-fold with 10 microM). These expressions may represent a possible consortium of mechanisms by which the cells protect themselves against nonylphenol-induced stresses. To the best of our knowledge, this is the first study on the effects of nonylphenol on Caco-2 cells.
Caco-2 Cells↗
Long-term effect of maternal obesity on pancreatic beta cells of offspring: reduced beta cell adaptation to high glucose and high-fat diet challenges in adult female mouse offspring.
AIM/HYPOTHESIS: Obesity is a global problem with high risks of cardiovascular diseases, stroke and type 2 diabetes. It is well known that maternal obesity affects offspring by inducing malformation, functional abnormalities in many organs and cells, and by increased risk of obesity and type 2 diabetes. However, little is known about abnormalities induced by maternal obesity in pancreatic beta cells of offspring. METHODS: We used mouse mothers with the Agouti yellow modification on a C57BL/6 background as a maternal model of normoglycaemic obesity, and produced Agouti-negative offspring. Half of the offspring were fed a high-fat diet. Offspring glucose tolerance was tested at different ages, and animals were killed at 50 weeks of age for islet function analysis. RESULTS: Maternal obesity impaired glucose tolerance in female offspring fed a high-fat diet, and significantly reduced insulin secretion at 50 weeks of age in female offspring that had been fed a normal diet and high-fat diet. Insulin secretion and glucose potentiation from these islets were significantly reduced. Islet protein, DNA and insulin contents were increased while glyceraldehyde-3-phosphate dehydrogenase and transketolase activities were reduced in female offspring. CONCLUSIONS/INTERPRETATION: Our results indicate that maternal obesity has a long-term effect on the beta cells of female, but not of male, offspring, and leads to increased risk of gestational diabetes and type 2 diabetes in the offspring's later lives.
Acclimatization↗
Solid and papillary epithelial neoplasm of the pancreas with ossification: a report of two cases.
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Adult↗
Comparative study of the effects of several chemical and physical treatments on the activity of protease resistance and infectivity of scrapie strain 263K.
To study the influences of chemical and physical factors on the protease resistant activity in vitro and the infectivity in vivo of scrapie strain 263K, PrPSc from the hamsters infected intracerebrally with scrapie strain 263K were treated with several commonly used disinfection methods, including sodium hydroxide (NaOH), sodium hypochlorite (NaOCl), heating or autoclaving at 80, 100, 121 and 134 degrees C in the solutions with or without 3% sodium dodecyl sulphate (SDS). The protease resistance of PrPSc was analysed by a proteinase K (PK) digesting Western blot and the infectivity of PrPSc was analysed by intracerebral (i.c.) inoculation into experimental hamsters. The results showed that PrPSc signals were removed in the preparations treated with NaOH higher than 0.05 mol/l, NaOCl higher than 0.1%, autoclaved over 121 degrees C, or heated over 80 degrees C in the presence of 3% SDS. Animal challenges revealed that mixing with 2 mol/l NaOH or 2% NaOCl, autoclaving at 134 degrees C, as well as heating at 100 degrees C or autoclaving at 121 degrees C in the solutions with 3% SDS completely blocks the transmission of scrapie 263K in this experimental situation. It is obvious that the removal of PK resistance of PrPSc happened at relatively lower concentration chemicals or lower temperature, while elimination of the infectivity needs more vigorous conditions. Our data provide the useful evidences for several commonly used methods to inactivate TSEs agent and suggest that it is inappropriate to use PrPSc as a surrogate for TSEs infectivity in inactivation experiments.
Animals↗
Localization of am3 using EL congenic mouse strains.
EL/Sea mice have 100% incidence of the absence of third molars (M3). Our previous linkage analysis using EL/Sea and MSM/Msf mouse strains provides statistical evidence of a major locus for the absence of M3, designated am3, of EL/Sea at the middle region of chromosome 3. To obtain independent evidence for linkage and more precisely determine the location of the am3 locus, we generated EL/Sea congenic strains for am3 in which the restricted interval of chromosome 3 of EL/Sea was replaced by an MSM/Msf-derived homologue. EL/Sea congenic mice that were either heterozygous or homozygous for the MSM/Msf-derived interval exhibited a significant decrease in the incidence of the absence of third molars, confirming previous genome scan results. These results confine the am3 locus to an approximately 4.4-cM region, and demonstrate that other unmapped genes are also involved in the absence of M3 in EL/Sea mice.
Animals↗
Partition of antimicrobial additives in an intravenous emulsion and their effect on emulsion physical stability.
A number of antimicrobial agents are potentially applicable to the preservation of small-volume parenteral emulsions. However, the physical stability of these emulsions is of paramount importance in ensuring their safety, and it is possible that antimicrobial additives could reduce the emulsion stability by a number of mechanisms. We have studied the effects of several antimicrobial agents on the physical stability of Diprivan, an intravenous anaesthetic emulsion. A particular problem is that many antimicrobial additives require an acidic pH in order to be effective (e.g. sodium benzoate, sodium metabisulphite) and the emulsion surface potential is insufficient to stabilize the emulsion to coalescence under these conditions. In addition several antimicrobial agents (e.g. methyl paraben and benzoic acid) partition into the oil phase of the emulsion, requiring the use of increased concentrations to remain effective. We describe an assay technique to quantify the oil partition, liposomal partition, and droplet surface adsorption of the additives. This illustrates that significantly more additive is partitioned out of the water phase than might be predicted from simple oil/water partition experiments.
Anti-Infective Agents↗
Enhanced rat beta-cell proliferation in 60% pancreatectomized islets by increased glucose metabolic flux through pyruvate carboxylase pathway.
Islet beta-cell proliferation is a very important component of beta-cell adaptation to insulin resistance and prevention of type 2 diabetes mellitus. However, we know little about the mechanisms of beta-cell proliferation. We now investigate the relationship between pyruvate carboxylase (PC) pathway activity and islet cell proliferation 5 days after 60% pancreatectomy (Px). Islet cell number, protein, and DNA content, indicators of beta-cell proliferation, were increased two- to threefold 5 days after Px. PC and pyruvate dehydrogenase (PDH) activities increased only approximately 1.3-fold; however, islet pyruvate content and malate release from isolated islet mitochondria were approximately threefold increased in Px islets. The latter is an indicator of pyruvate-malate cycle activity, indicating that most of the increased pyruvate was converted to oxaloacetate (OAA) through the PC pathway. The contents of OAA and malate, intermediates of the pyruvate-malate cycle, were also increased threefold. PDH and citrate content were only slightly increased. Importantly, the changes in cell proliferation parameters, glucose utilization, and oxidation and malate release were partially blocked by in vivo treatment with the PC inhibitor phenylacetic acid. Our results suggest that enhanced PC pathway in Px islets may have an important role in islet cell proliferation.
Animals↗
Genetic variation in XRCC1, sun exposure, and risk of skin cancer.
The XRCC1 gene is involved in the base excision repair pathway. We assessed the associations of polymorphisms and haplotypes in XRCC1 with skin cancer risk in a nested case-control study within the Nurses' Health Study (219 melanoma, 286 squamous cell carcinoma (SCC) and 300 basal cell carcinoma (BCC), and 873 controls). We genotyped four haplotype-tagging single-nucleotide polymorphisms (Arg194Trp, C26602T, Arg399Gln, and Gln632Gln). There was no significant difference in frequency distribution between cases and controls for any of the five inferred common haplotypes. We observed that the 399Gln allele was inversely associated with SCC risk. This inverse association was only seen among those who had five or more lifetime sunburns, those with a family history of skin cancer, and those in the highest tertile of cumulative sun exposure in a bathing suit, but not among those with low risk defined by these risk factors. We also observed a significant association of the carriage of 194Trp allele with increased SCC risk, which was modified by family history of skin cancer. These two polymorphisms were not associated with BCC or melanoma risk. Our data suggest that the Arg194Trp and Arg399Gln polymorphisms may be differently associated with skin cancer risk according to exposure dose and skin cancer type.
Adult↗
Ancestral echinoderms from the Chengjiang deposits of China.
Deuterostomes are a remarkably diverse super-phylum, including not only the chordates (to which we belong) but groups as disparate as the echinoderms and the hemichordates. The phylogeny of deuterostomes is now achieving some degree of stability, especially on account of new molecular data, but this leaves as conjectural the appearance of extinct intermediate forms that would throw light on the sequence of evolutionary events leading to the extant groups. Such data can be supplied from the fossil record, notably those deposits with exceptional soft-part preservation. Excavations near Kunming in southwestern China have revealed a variety of remarkable early deuterostomes, including the vetulicolians and yunnanozoans. Here we describe a new group, the vetulocystids. They appear to have similarities not only to the vetulicolians but also to the homalozoans, a bizarre group of primitive echinoderms whose phylogenetic position has been highly controversial.
Animals↗
Conjugation metabolism of acetaminophen and bilirubin in extrahepatic tissues of rats.
An anhepatic rat model was used to explore the extrahepatic conjugating metabolism of acetaminophen and serum bilirubin. The recovery of glucuronide- and sulfate-acetaminophen was 47.5% in normal control and 13.4% in model rats in the urine collected for 6 h after administration of acetaminophen 20 mg kg(-1). Following the increase of acetaminophen dose to 150 mg kg(-1), the recovery of urinary glucuronide-acetaminophen increased by 53.9% in normal control; but it decreased by 36.4% in model rats. In contrast to normal control, the pretreatment with phenobarbital did not affect acetaminophen and its metabolite levels in plasma and urine in model rats. After the establishment of anhepatic model the serum direct bilirubin rose dramatically. Urinary bilirubin test was positive in model rats, but not in normal control. No changes were observed in serum total bilirubin and ratio of direct/total bilirubin after the pretreatment with ranitidine or phenobarbital 50 mg kg (-1), i.p. for 5 days in model rats. The results indicate that the glucuronide- and sulfate-acetaminophen formed in the extrahepatic tissues of model rats is 28.2% of normal control, serum free bilirubin can be transformed into conjugated bilirubin in extrahepatic tissues, and the regulation mechanism of phase II conjugating enzymes is different between the hepatic and extrahepatic tissues.
Acetaminophen↗
Differential involvement of Bax and Bak in TRAIL-mediated apoptosis of leukemic T cells.
TRAIL-induced apoptosis has been considered a promising therapeutic approach for tumors that are resistant to chemotherapy, which is usually mediated via mitochondrial apoptotic cascades. Recent studies have shown that in certain cancer cells, TRAIL-mediated apoptosis is also dependent on mitochondrial involvement, suggesting that similar mechanisms of resistance to chemotherapy might be implicated in the resistance of tumor cells to TRAIL. We have used TRAIL-resistant leukemic cells that are deficient in both Bax and Bak to determine the roles of these Bcl-2 members in TRAIL-mediated apoptosis. Exposure of these cells to TRAIL did not have an impact on cell viability, although it induced the processing of caspase-3 to its active p20 subunit. The activity of the p20 caspase-3 appeared to be inhibited as no autoprocessing of this p20 subunit or cleavage of known caspase-3 substrates were detected. Also, in the absence of Bax and Bak, no release of mitochondrial apoptogenic proteins was observed following TRAIL treatment. Adenoviral transduction of the Bax, but not the Bak gene, to the Bax/Bak-deficient leukemic cells rendered them TRAIL-sensitive as assessed by enhanced apoptotic death and caspase-3 processing. These findings demonstrate preferential utilization of Bax over Bak in leukemic cell response to specific apoptotic stimulation.
Adenoviridae↗