[International expert consensus on gene therapy for hereditary hearing loss: based on clinical trials].
Explore the source record for details and available documents.
Journal Article↗
Biomedical subjects
S Han
Publications and source records attributed to S Han.
High frequency occurrence of 1-OPRD variant of PRNP gene in gastric cancer cell lines and Chinese population with gastric cancer.
The prion protein gene PRNP encodes PrPc and PrPsc, causing a number of neurological disorders. Approximately 10-15% of human prion disease is inherited and more than 20 pathogenic mutations have been found. Most of the genetic alterations are point mutations, with the exception of genetic insertions of one to nine extra octapeptide repeats occurring in the important octapeptide-coding region. Our previous work showed that PrPc was overexpressed in gastric cancer. We wondered whether mutations of PrPc existed in human gastric cancer. DNA sequencing and gel electrophoresis were used to determine the possible mutation of PrPc in patients and cell lines of gastric cancer. We found that 1-OPRD (one octapeptide-repeat deletion) homozygosity or heterozygosity exists in several gastric cancer cell lines, e.g. MKN28 and KatoIII are homozygous for 1-OPRD, and SGC7901 and BGC-823 are heterozygous for 1-OPRD. The mutation frequency in tissues of gastric cancer cases is significantly higher than that in the common population (p<0.05). All positive cases in gastric cancer were found to be heterozygous for 1-OPRD. Further study of the variant may be helpful in understanding the mechanisms of occurrence and development of clinical gastric carcinoma as well as the biology of the mysterious gene PRNP.
Adolescent↗
Cox-2 expression on tissue microarray of breast cancer.
AIM: To measure cyclooxygenase-2 (Cox-2) expression in a series of breast cancers and evaluate its potential as a predictive marker for doxorubicin chemotherapy. PATIENTS AND METHODS: Cox-2 expression was analyzed in 178 node-positive patients treated with doxorubicin-based adjuvant chemotherapy by immunohistochemistry on tissue microarray (TMA). RESULTS: Cox-2 was over-expressed in 70 out of the 178 invasive breast cancers. Cox-2 expression was significantly increased in undifferentiated tumors. There was no significant association between Cox-2 over-expression and tumor size, histologic grade, and estrogen receptor expression. Disease-free survival and overall survival of the patients having Cox-2 expressing tumor were significantly decreased when compared with the patients having Cox-2 negative tumor (p=0.009 for DFS, p=0.011 for OS). CONCLUSION: Cox-2 expression may represent an aggressive phenotype of breast cancer which is resistant to doxorubicin.
Antibiotics, Antineoplastic↗
Microscopic polyangiitis complicated by cerebral haemorrhage.
Explore the source record for details and available documents.
Adult↗
Downregulation of E-cadherin by hepatitis B virus X antigen in hepatocellullar carcinoma.
Hepatitis B virus (HBV)-encoded X antigen (HBxAg) contributes to the development of hepatocellular carcinoma (HCC). A frequent characteristic of HCC is reduced or absent expression of the cell adhesion protein, E-cadherin, although it is not known whether HBxAg plays a role. To address this, the levels of E-cadherin were determined in HBxAg-positive and -negative HepG2 cells in culture, and in tumor and surrounding nontumor liver from a panel of HBV carriers. The results showed an inverse relationship between HBxAg and E-cadherin expression both in tissue culture and in vivo. In HBxAg-positive cells, E-cadherin was suppressed at both the mRNA and protein levels. This was associated with hypermethylation of the E-cadherin promoter. Depressed E-cadherin correlated with HBxAg trans-activation function, as did the migration of HepG2 cells in vitro. Decreased expression of E-cadherin was also associated with the accumulation of beta-catenin in the cytoplasm and/or nuclei in tissues and cell lines, which is characteristic of activated beta-catenin. Additional work showed that HBxAg-activated beta-catenin. Together, these results suggest that the HBxAg is associated with decreased expression of E-cadherin, accumulation of beta-catenin in the cytoplasm and nucleus, and increased cell migration, which may contribute importantly to hepatocarcinogenesis.
Cadherins↗
In vitro endothelial potential of human UC blood-derived mesenchymal stem cells.
BACKGROUND: Human mesenchymal stem cells (MSC) possess powerful ex vivo expansion and versatile differentiation potential, placing themselves at the forefront of the field of stem cell-based therapy and transplantation. Of high clinical relevance is the endothelial differentiation potential of MSC, which can be used to treat various forms of ischemic vascular disease. METHODS: We investigated whether human umbilical cord blood (UCB)-derived MSC are able to differentiate in vitro along an endothelial lineage, by using flow cytometry, RT-PCR and immunofluorescence analyzes, as well as an Ab array method. RESULTS: When the cells were incubated for up to 3 weeks in the presence of VEGF, EGF and hydrocortisone, they began to express a variety of endothelial lineage surface markers, such as Flk-1, Flt-1, VE-Cadherin, vWF, VCAM-1, Tie-1 and Tie-2, and to secrete a specific set of cytokines. Differentiated cells were also found to be able to uptake low-density lipoprotein and form a tubular network structure. DISCUSSION: These observations have led us to conclude that UCB-derived MSC retain endothelial potential that is suitable for basic and clinical studies aimed at the development of vasculature-directed regenerative medicine.
Antigens, CD↗
Utilization of a cryptic noncanonical donor splice site in the KRT14 gene causes a mild form of epidermolysis bullosa simplex.
Explore the source record for details and available documents.
Epidermolysis Bullosa Simplex↗
HER2 status in pure ductal carcinoma in situ and in the intraductal and invasive components of invasive ductal carcinoma determined by fluorescence in situ hybridization and immunohistochemistry.
AIM: To determine the HER2 status of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of the breast. The increased prevalence of HER2 amplification and overexpression in DCIS is considered to be maintained in the intraductal component of IDC; however, HER2 amplification and overexpression are detected much less in IDC. METHODS AND RESULTS: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed to detect HER2 in 270 IDCs with an intraductal component and in 50 pure DCIS samples; IHC was also performed in 116 metastatic nodes. HER2 was found to be amplified in 77 cases (28.5%) and overexpressed in 79 (29.3%) of the 270 IDCs. HER2 amplification was similar between intraductal and invasive components of the same tumour. The concordance for HER2 status between invasive and intraductal components of individual tumours was 98.5% and 99.3% by FISH and IHC, respectively. HER2 was amplified in 25 (50%) of the 50 pure DCIS samples. HER2 overexpression in metastatic nodes resembled the HER2 status in the primary tumour for 108 (93.1%) of 116 cases (kappa =0.831). CONCLUSION: Our study indicates that the intraductal component of IDC may differ biologically when compared with pure DCIS. HER2 appears to lack a critical role in the progression from DCIS to IDC and HER2 status is maintained in metastatic lesions.
Adult↗
Prevalence and risk factors for diabetes mellitus in moderate term survivors of liver transplantation.
The prevalence and risk factors for diabetes mellitus after liver transplantation are not well understood. Thus, we sought to identify independent risk factors for the development of diabetes after liver transplantation using currently accepted medical criteria. We studied the prevalence and risk factors in 253 adult recipients transplanted at UCLA between January 1998 and December 2002. Analysis of the retrospective data was performed using demographic, immunosuppression and liver disease variables. Factors found to be significant on a univariate analysis were further studied in a multivariate analysis. There were 158 men and 95 women in our study. The mean age was 51.4 +/- 11.0 years. The mean [+/- standard deviation (SD) pretransplant body mass index was 26.7 (+/-5.1). Most patients were transplanted for hepatitis C (HCV). The prevalence of diabetes after transplantation was 17.8%. In a multivariate analysis only gender [odds ratio (OR) = 0.37; p = 0.02] was independently predictive of the development of diabetes. This study in a large liver transplant recipient population identifies male gender as an independent risk factor for the development of diabetes. Follow-up studies are needed to assess the impact of diabetes, and its intervention on post-transplant morbidity and mortality.
Diabetes Mellitus↗
Dissimilatory arsenate and sulfate reduction in sediments of two hypersaline, arsenic-rich soda lakes: Mono and Searles Lakes, California.
A radioisotope method was devised to study bacterial respiratory reduction of arsenate in sediments. The following two arsenic-rich soda lakes in California were chosen for comparison on the basis of their different salinities: Mono Lake (approximately 90 g/liter) and Searles Lake (approximately 340 g/liter). Profiles of arsenate reduction and sulfate reduction were constructed for both lakes. Reduction of [73As]arsenate occurred at all depth intervals in the cores from Mono Lake (rate constant [k] = 0.103 to 0.04 h(-1)) and Searles Lake (k = 0.012 to 0.002 h(-1)), and the highest activities occurred in the top sections of each core. In contrast, [35S]sulfate reduction was measurable in Mono Lake (k = 7.6 x10(4) to 3.2 x 10(-6) h(-1)) but not in Searles Lake. Sediment DNA was extracted, PCR amplified, and separated by denaturing gradient gel electrophoresis (DGGE) to obtain phylogenetic markers (i.e., 16S rRNA genes) and a partial functional gene for dissimilatory arsenate reduction (arrA). The amplified arrA gene product showed a similar trend in both lakes; the signal was strongest in surface sediments and decreased to undetectable levels deeper in the sediments. More arrA gene signal was observed in Mono Lake and was detectable at a greater depth, despite the higher arsenate reduction activity observed in Searles Lake. A partial sequence (about 900 bp) was obtained for a clone (SLAS-3) that matched the dominant DGGE band found in deeper parts of the Searles Lake sample (below 3 cm), and this clone was found to be closely related to SLAS-1, a novel extremophilic arsenate respirer previously cultivated from Searles Lake.
Arsenates↗
Human hepatocyte growth factor levels in patients undergoing thoracic operations.
Human hepatocyte growth factor (hHGF) is the most potent mitogen identified for alveolar type II cells, and may have other important functions in the repair of the alveolar epithelium and compensatory lung growth. A study was conducted to evaluate the changes of serum hHGF levels in patients who underwent thoracic surgical procedures. The patients comprised 17 males and 14 females with a mean age of 47.1+/-13.5 yrs, who underwent either lung resection (LR group) or nonlung resection (nonLR group) thoracic procedures. The changes of hHGF levels were analysed in the pre- and post-operative periods in both groups. The pre-operative hHGF levels did not differ between the LR and the nonLR groups, which were 333.2+/-72.9 pg x mL(-1) and 343.6+/-125.3 pg x mL(-1), respectively. The hHGF levels in the LR group significantly increased up to 433.6+/-128.1 pg x mL(-1) and 430.8+/-128.2 pg x mL(-1) in post-operative days 1 and 3, respectively. However, the same levels in the nonLR group appeared as 333.2+/-77.0 pg x mL(-1) and 311.9+/-73.0 pg x mL(-1), respectively. In conclusion, the increases of serum human hepatocyte growth factor levels following pulmonary resection may imply the important role of human hepatocyte growth factor in lung regeneration or compensatory lung growth in humans.
Adolescent↗
New process control strategy for wastewater chlorination and dechlorination using ORP/pH.
Due to its efficiency and relatively low capital demanding, many wastewater treatment plants have applied chlorination for disinfection of treated wastewater before discharging it. However, determination of optimal doses of chlorine for chlorination and sulfite for dechlorination, which removes residual chlorine, should made to guarantee complete destruction of microorganisms in treated wastewater and to protect aquatic life in a receiving stream. In this study, a new ORP/pH based approach to determine endpoints of breakpoint chlorination and of dechlorinating titration and to optimize doses of chlorine and sulfite. In this new method, significant points on the ORP and pH profiles occurring during the titrations for chlorination and dechlorination were utilized to determine chlorine demand and sulfite dosage.
Chlorine↗
New ORP/pH based control strategy for chlorination and dechlorination of wastewater: pilot scale application.
Due to its efficiency and low capital demands, chlorination has been widely used for disinfection in many wastewater treatment plants. Since the oxidation power of free chlorine is bigger than combined chlorines which are formed from the reaction between chlorine and reducing agents in water (especially, NH4+ and organic nitrogen), for effective disinfection, excess amount of chlorine is added until all the reducing agents are oxidized and free chlorine is available. After chlorination, chlorine residues in wastewater are usually reduced with SO2 or sulfites before the treated wastewater is discharged, since they are toxic to aquatic life. Addition of excess amount of SO2 or sulfite should be avoided. Otherwise, they consume dissolved oxygen in a river or stream and may have adverse impact on the aquatic life. Determination of wastewater chlorine demand and of sulfite dosages for dechlorination has been a challenge to WWTP operators, due to the dynamic characteristics of wastewater. Recently, a new ORP/pH based approach to determine chlorine demand and sulfite dosage was proposed. The method utilizes significant points occurring on the pH and ORP profiles during chlorination and dechlorination titrations. In this study, the proposed automatic titration system has been implemented into a control system to optimize chlorine and sulfite doses for a pilot scale chlorination/dechlorination system. In short, the disinfection system with the pH/ORP based controller showed very successful results; complete inactivation of total coliforms, and almost zero residual chlorines and high DO in its effluent.
Chloramines↗
Time-of-flight flow imaging using NMR remote detection.
A time-of-flight imaging technique is introduced to visualize fluid flow and dispersion through porous media using NMR. As the fluid flows through a sample, the nuclear spin magnetization is modulated by rf pulses and magnetic field gradients to encode the spatial coordinates of the fluid. When the fluid leaves the sample, its magnetization is recorded by a second rf coil. This scheme not only facilitates a time-dependent imaging of fluid flow, it also allows a separate optimization of encoding and detection subsystems to enhance overall sensitivity. The technique is demonstrated by imaging gas flow through a porous rock.
Journal Article↗
Faecal calprotectin in the assessment of Crohn's disease activity.
BACKGROUND: Clinical and laboratory assessment of activity in Crohn's disease (CD) correlate poorly with endoscopic findings. Calprotectin is a calcium-binding protein abundant in neutrophil cytosol, and extremely stable in faeces. Faecal calprotectin (FC) is an excellent surrogate marker of neutrophil influx into the bowel lumen. AIM: To assess whether FC concentration from a spot stool sample reliably detects active inflammation in patients with CD. DESIGN: Cross-sectional comparative study. METHODS: Subjects had a previously confirmed diagnosis of CD and were suspected on clinical grounds to be in the midst of a relapse. Thirty-five entered the study; they underwent radiolabelled white cell scanning (WCS) and had a stool sample collected for calprotectin measurement on the same day. A Crohn's disease activity index (CDAI) was also calculated for each. The WCS scans were scored at six standard sites to give a mean total, 'extent', 'severity' and 'combined extent and severity' scores. RESULTS: FC was significantly and positively correlated with mean total (r = 0.73, p < 0.001), 'extent' (r = 0.71, p < 0.001), 'severity' (r = 0.64, p < 0.001) and combined 'extent and severity' WCS scores (r = 0.71, p < 0.001). A cut-off of faecal calprotectin > 100 microg/g gave a sensitivity of 80%, specificity of 67%, positive predictive value of 87% and a negative predictive value of 64% in identifying those with and without any inflammation on WCS. There was, however, no significant correlation between CDAI and mean total WCS score (r = 0.21, p = 0.24), nor between CDAI and FC (r = 0.33, p = 0.06). DISCUSSION: While the CDAI does not accurately reflect inflammatory activity in CD, a one-off FC reliably detects the presence or absence of intestinal inflammation in adult patients with CD, compared to WCS.
Adult↗
Effects of epidural naloxone on pruritus induced by epidural morphine: a randomized controlled trial.
BACKGROUND: Epidural morphine produces prolonged analgesia but has many side effects including pruritus. Naloxone is an antagonist that can reverse the side effects of morphine. METHOD: We studied the effects of continuously administered epidural naloxone mixed with morphine on side effects and analgesia in a randomized, double blind, two-armed study. Fifty-eight pregnant women undergoing cesarean section were enrolled. All patients received a 4-mg epidural bolus of morphine in the post-anesthetic care unit. After this, patients in group M (n=28) received continuous epidural morphine (6 mg over 48 h) in 0.1% bupivacaine; patients in group N (n=30) received an epidural infusion containing naloxone (1.2 mg over 48 h) and morphine (6 mg over 48 h) in 0.1% bupivacaine. The infusion rate was 2 mL/h. RESULTS: The incidence (82% versus 47%) and severity of pruritus were lower in group N than group M (P=0.001). There were no significant differences in pain score or in the incidence of nausea, vomiting or urinary disturbance between groups. CONCLUSION: Continuous epidural infusion of naloxone combined with morphine is effective in reducing the incidence and severity of pruritus induced by epidural morphine.
Adult↗
Age-associated deficiency in activation-induced up-regulation of telomerase activity in CD4+ T cells.
For lymphocytes, the ability to undergo clonal expansion is crucial for effective immune function. Telomerase activity compensates for telomere erosion during cell division and contributes to the capability of lymphocytes to maintain cellular proliferation. In addition, telomerase activity may have a fundamental role in cell growth and survival. To determine whether age-related immune dysfunction is associated with an abnormality in telomerase activity, we investigated telomerase activity in T cell populations from young adult and aged mice. Our data show that the ability of T cells from aged mice to up-regulate telomerase activity after activation was significantly diminished. This age-related deficiency in telomerase induction is restricted to CD4(+) T cells, as CD8(+) T cells retain the capability to up-regulate telomerase activity. These findings reinforce the notion that age-related immune dysfunction results mainly from impairment of helper T cells, and may have important implications for designing novel means to improve immune responses in aged individuals by enhancing CD8(+) T cell functions, which are crucial in both viral and tumour immunity.
Aging↗
A novel mechanism prevents the development of hypertension during chronic cold stress.
1 Chronic cold exposure of rats (7 days in a cold room at 4 degrees C) attenuated the sympathetic nerve stimulation (NS)-induced overflow of noradrenaline (NE) (measured by high-performance liquid chromatography, coupled to electrochemical detection) appearing in the perfusate/superfusate of the perfused mesenteric arterial bed as well as the increase in the perfusion pressure. 2 The same type of cold exposure resulted in an increase in tyrosine hydroxylase (TH) gene expression measured in the superior cervical ganglion and NE content measured in the mesenteric artery obtained from cold-exposed rats. 3 Addition of sodium nitroprusside, a nitric oxide (NO) donor, to the buffer perfusing the mesenteric arterial bed obtained from rats maintained at room temperature also resulted in an attenuation of the NS-induced overflow of NE and increase in perfusion pressure. 4 N(c)-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, placed in the drinking water prevented the attenuation of the pre- and post-junctional responses to NS of the mesenteric arterial bed obtained from cold-exposed rats. 5 L-NAME treatment also increased the cold-induced elevation of blood pressure seen in whole animals. 6 The present results are consistent with the idea that cold exposure leads to a concomitant increase in sympathetic nerve activity and production of NO. We hypothesize that the increase in production and release of NO results in a decrease in the biologically active form of NE despite increased synthesis and release of the catecholamine. 7 It is concluded that the above-mentioned interactions serve as a protective mechanism offsetting the increased release and action of NE from sympathetic nerves and thus preventing the development of hypertension.
Animals↗