Biomedical subjects

W Zheng

Publications and source records attributed to W Zheng.

At least 109 records · Page 6Linked to original sources

PubMed2000

Yohimbine dimers exhibiting binding selectivities for human alpha2a- versus alpha2b-adrenergic receptors.

A series of yohimbine dimers was prepared and evaluated at the human alpha2a- and alpha2b-adrenergic receptors (ARs) expressed in Chinese hamster ovary (CHO) cells. All dimers display higher binding selectivities for alpha2a versus alpha2b subtype than yohimbine, and four compounds (3d, 3e, 3g and 3i) represent the most potent and alpha2a versus alpha2b-AR selective ligands identified so far.

Adrenergic alpha-2 Receptor Antagonists↗

PubMed2000

Determination of harmane and harmine in human blood using reversed-phased high-performance liquid chromatography and fluorescence detection.

A number of tremorogenic beta-carboline alkaloids have been found in common plant-derived foodstuffs, beverages, and inhaled substances. Because of their natural presence in the food chain, there is a growing concern regarding the potential risks of certain essential tremors associated with the long-term, low-level dietary exposure to these alkaloids. The purpose of this study was to develop an effective analytical method to determine blood levels of two major beta-carboline derivatives, harmane and harmine. Human blood was extracted with ethyl acetate and methyl-t-butyl ether (2:98) under an alkaline condition. After evaporation of organic solvent, the samples were reconstructed in methanol. The samples were fractionated on a 250 x 4.6-mm C18 reversed-phase column with an isocratic mobile system consisting of 17.5 mM potassium phosphate buffer (ph 6.5) and methanol (30:70), followed by an on-line fluorescence detection. The method had the detection limit to determine 206 and 81 pg/ml of harmane and harmine, respectively, in 10 ml of human blood. The intraday precision (C.V.) at 25 ng/ml was less than 6.7 and 3.4% for harmane and harmine, respectively. The interday precision was 7.3% for harmane and 5.4% for harmine. The method has proven sensitive, reproducible, and thus useful for both laboratory and clinical studies of beta-carboline toxicities.

Animals↗

PubMed2000

Ionizing radiation activates the ATM kinase throughout the cell cycle.

The ATM protein kinase is a critical intermediate in a number of cellular responses to ionizing irradiation (IR) and possibly other stresses. ATM dysfunction results in abnormal checkpoint responses in multiple phases of the cell cycle, including G1, S and G2. Though downstream targets of the ATM kinase are still being elucidated, it has been demonstrated that ATM acts upstream of p53 in a signal transduction pathway initiated by IR and can phosphorylate p53 at serine 15. The cell cycle stage-specificity of ATM activation and p53Ser15 phosphorylation was investigated in normal lymphoblastoid cell line (GM536). Ionizing radiation was found to enhance the kinase activity of ATM in all phases of the cell cycle. This enhanced activity was apparent immediately after treatment of cells with IR, but was not accompanied by a change in the abundance of the ATM protein. Since IR activates the ATM kinase in all phases of the cell cycle, DNA replication-dependent strand breaks are not required for this activation. Further, since p53 protein is not directly required for IR-induced S and G2-phase checkpoints, the ATM kinase likely has different functional targets in different phases of the cell cycle. These observations indicate that the ATM kinase is necessary primarily for the immediate response to DNA damage incurred in all phases of the cell cycle.

Ataxia Telangiectasia↗

PubMed2000

The Discovery of a Second Field Methane Brown Dwarf from Sloan Digital Sky Survey Commissioning Data.

We report the discovery of a second field methane brown dwarf from the commissioning data of the Sloan Digital Sky Survey (SDSS). The object, SDSS J134646.45-003150.4 (hereafter SDSS 1346-00), was selected because of its very red color and stellar appearance. Its spectrum between 0.8 and 2.5 µm is dominated by strong absorption bands of H2O and CH4 and closely mimics those of Gliese 229B and SDSS 162414.37+002915.6 (hereafter SDSS 1624+00), two other known methane brown dwarfs. SDSS 1346-00 is approximately 1.5 mag fainter than Gliese 229B, suggesting that it lies about 11 pc from the Sun. The ratio of flux at 2.1 µm to that at 1.27 µm is larger for SDSS 1346-00 than for Gliese 229B and SDSS 1624+00, which suggests that SDSS 1346-00 has a slightly higher effective temperature than the others. Based on a search area of 130 deg2 and a detection limit of z*=19.8, we estimate a space density of 0.05 pc-3 for methane brown dwarfs with Teff approximately 1000 K in the 40 pc3 volume of our search. This estimate is based on small-sample statistics and should be treated with appropriate caution.

Journal Article↗

PubMed2000

Population-based, case-control study of HER2 genetic polymorphism and breast cancer risk.

BACKGROUND: Alterations of the HER2 (also known as erbB-2 or neu) proto-oncogene have been implicated in the carcinogenesis and prognosis of breast cancer. A polymorphism at codon 655 (GTC/valine to ATC /isoleucine [Val(655)Ile]) in the transmembrane domain-coding region of this gene has been identified and may be associated with the risk of breast cancer. We evaluated this hypothesis in a subgroup of women who participated in a large-scale, population-based, case-control study of breast cancer in Shanghai, China. METHODS: Genomic DNA from 339 patients with breast cancer and 361 healthy control subjects was examined for the Val(655)Ile polymorphism with a polymerase chain reaction-restriction fragment-length polymorphism-based assay. All study subjects completed a structured questionnaire during an in-person interview. All P values are from two-sided tests. RESULTS: We found that 25.1% of the case patients and 21.7% of the control subjects were heterozygous for the Val allele and 3.2% of the case patients and 0. 3% of the control subjects were homozygous for this allele (P =.005). Compared with women with the Ile/Ile genotype, women who had the Ile/Val or Val/Val genotype had an elevated risk of breast cancer (odds ratio [OR] = 1.4; 95% confidence interval [CI] = 1.0-2.0; P =. 05) after adjustment for age, educational level, study period, history of breast fibroadenoma, leisure physical activity, and age at first live birth. The risk was elevated even more among women who were homozygous for the Val allele (OR = 14.1; 95% CI = 1.8-113.4). The association was more pronounced among younger women (</=45 years) than among older women (>45 years). The adjusted OR associated with the Val allele was 1.7 (95% CI = 1.1-2.6) for younger women and 1.0 (95% CI = 0.5-1.9) for older women. CONCLUSIONS: Results of this study suggest that polymorphisms of the HER2 gene may be important susceptibility biomarkers for breast cancer risk, particularly among younger women.

Adult↗

PubMed2000

Normal patterns of angiogenesis and extracellular matrix deposition in chick chorioallantoic membranes are disrupted by mainstream and sidestream cigarette smoke.

The adverse effects of cigarette smoke on mature blood vessels are well established, whereas little is known about the influence of smoke on blood vessel development. To determine if cigarette smoke alters angiogenesis, chick chorioallantoic membranes (CAMs) were exposed for 4 days to culture medium (control) or to mainstream (MS) or sidestream (SS) smoke solution, and then blood vessel patterns were compared in blind tests. In contrast to the normal tree-like branching of control blood vessels, smoke-treated CAMs often had vessels that ran parallel to each other without much branching. A significant increase in the number of fibroblasts was observed in histological sections of treated CAMs, and this increase correlated with alterations in extracellular matrix components. Many more matrix fibrils were observed in treated CAMs than in controls using scanning electron microscopy. Immunohistochemistry showed that type III collagen was distributed in a tight band adjacent to the endoderm in controls but was distributed throughout the mesoderm in both treatment groups. Western blots confirmed that both type I and type III collagen were more abundant in treated CAMs than in controls. Fibronectin, which was localized immunohistochemically in the basal laminae and mesodermal matrix of controls, increased in abundance in CAMs treated with SS smoke solutions. Hyaluronic acid, which was present in a dense band subjacent to the capillary plexus of control CAMs, was greatly reduced in MS-treated CAMs and was absent in SS-treated CAMs. These observations demonstrate that both MS and SS cigarette smoke solutions caused abnormal pattern formation of CAM blood vessels and altered the composition of the extracellular matrix in the CAM mesoderm.

Allantois↗

PubMed2000

Twinship and risk of postmenopausal breast cancer.

BACKGROUND: Intrauterine exposure to high levels of endogenous estrogens has been hypothesized to increase the risk of breast cancer. Because estrogens and other pregnancy hormones are substantially elevated in twin pregnancies, and possibly more so in dizygotic twin pregnancies, we evaluated the association between aspects of twin membership (i.e., belonging to a twin pair) and the risk of breast cancer. METHODS: In a cohort of 29 197 postmenopausal Iowa women with no prior diagnosis of cancer (except for nonmelanoma skin cancer), breast cancer risk factors were determined by use of a mailed questionnaire in 1986 (baseline); twin membership, sex of the twin, and zygosity were determined by use of a follow-up questionnaire in 1992. RESULTS: Within the cohort, 1.8% (n = 538) of the women reported being a twin; of these, 24% (n = 130) were monozygotic twins, 63% (n = 337) were dizygotic twins, and 13% (n = 71) did not know their zygosity. From 1986 through 1996, 1230 breast cancers in the cohort were ascertained by linkage to the Iowa Cancer Registry. Compared with singletons, women who belonged to a twin pair were at elevated risk of breast cancer (multivariate-adjusted risk ratio [RR] = 1.72; 95% confidence interval [CI] = 1.22-2.42), with adjustment for educational level, family history of breast cancer, height, body mass index, body fat distribution, age at menarche, age at first live birth, use of hormone replacement therapy, and alcohol use. Multivariate-adjusted risk was elevated (in comparison with singletons) if the sex of the other twin was female (RR = 1.82; 95% CI = 1.20-2.75); however, this risk was limited to female dizygotic twins (RR = 2.14; 95% CI = 1. 21-3.79), since no excess risk was evident for monozygotic twins (RR = 1.04; 95% CI = 0.43-2.50). The risk to women with a male twin was also elevated (RR = 1.49; 95% CI = 0.80-2.78) in comparison with singletons, but this estimate was not statistically significant. CONCLUSIONS: This cohort study lends further support to the theory that there are important intrauterine influences on carcinogenesis of the breast.

Aged↗

PubMed2000

In vitro selection and characterization of a highly efficient Zn(II)-dependent RNA-cleaving deoxyribozyme.

A group of highly efficient Zn(II)-dependent RNA-cleaving deoxyribozymes has been obtained through in vitro selection. They share a common motif with the '8-17' deoxyribozyme isolated under different conditions, including different design of the random pool and metal ion cofactor. We found that this commonly selected motif can efficiently cleave both RNA and DNA/RNA chimeric substrates. It can cleave any substrate containing rNG (where rN is any ribo-nucleotide base and G can be either ribo- or deoxy-ribo-G). The pH profile and reaction products of this deoxyribozyme are similar to those reported for hammerhead ribozyme. This deoxyribozyme has higher activity in the presence of transition metal ions compared to alkaline earth metal ions. At saturating concentrations of Zn(2+), the cleavage rate is 1.35 min(-1)at pH 6.0; based on pH profile this rate is estimated to be at least approximately 30 times faster at pH 7.5, where most assays of Mg(2+)-dependent DNA and RNA enzymes are carried out. This work represents a comprehensive characterization of a nucleic acid-based endonuclease that prefers transition metal ions to alkaline earth metal ions. The results demonstrate that nucleic acid enzymes are capable of binding transition metal ions such as Zn(2+)with high affinity, and the resulting enzymes are more efficient at RNA cleavage than most Mg(2+)-dependent nucleic acid enzymes under similar conditions.

Base Sequence↗

PubMed2000

Ovarian epithelial tumor growth promotion by follicle-stimulating hormone and inhibition of the effect by luteinizing hormone.

OBJECTIVES: The role of gonadotropins in ovarian epithelial cancer development is still controversial. Follicle-stimulating hormone receptor (FSHR) status in ovarian epithelial tumors (OETs) and their presumed precursor lesions has never been studied in detail. The objective of this study was to examine whether FSHR is expressed in OETs and to investigate the possible different roles of the gonadotropins in ovarian cancer development. METHODS: Twenty ovarian epithelial inclusions (entrapments or invaginations of ovarian surface epithelium) from benign ovaries and 60 OETs including 12 cystadenomas, 18 borderline tumors, and 30 carcinomas were examined for FSHR expression by using reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization (ISH), and immunohistochemistry (IHC). We also studied the mitogenic activity of FSH on two FSH and luteinizing hormone (LH) receptor-positive ovarian epithelial carcinoma cell lines (AO and 3AO) and on the modifying effect of LH on this activity. Growth-stimulating effects of the gonadotropins were tested in vitro with measurement of cell numbers, S-phase by flow cytometry, and changes in the cellular proliferative marker Ki-67. RESULTS: Positive FSHR mRNA expression by RT-PCR (the most sensitive method) was found in 100% of epithelial inclusions, 100% of cystadenomas, 94% of borderline tumors, and 60% of carcinomas. There was a nonstatistically significant trend of decreasing positivity with increasing carcinoma grade. ISH and IHC gave similar, but somewhat less sensitive, results. A dose-response effect was seen with FSH, with a 1.6-fold increase in cell numbers with a maximally stimulating FSH concentration of 40 IU/L for a period of 48 h. These proliferative cellular effects were not observed when the cells were stimulated by LH in the range 1 to 100 IU/L. Most significantly, the growth stimulating effects of FSH could be blocked by the simultaneous administration of LH. CONCLUSIONS: FSHR is present in the majority of ovarian epithelial inclusions and OETs. The steady decline of FSHR expression from benign cystadenoma to borderline tumor to carcinoma suggests that FSH may be needed in early ovarian cancer development. Gonadotropins, FSH and LH, may have different roles in ovarian cancer cell proliferation. FSH, not LH, may be an important ovarian epithelial cell growth-promoting factor. The "opposing" effect of LH on FSH stimulation may explain why high FSH levels at postmenopausal ages are not associated with great increases in ovarian cancer risk.

Adult↗

PubMed2000

Reduction of BRCA1 expression in sporadic ovarian cancer.

OBJECTIVE: The purpose of this study was to examine BRCA1 expression and its relationship to cell proliferation in sporadic ovarian epithelial tumors (OETs). METHODS: We investigated BRCA1 expression and cell proliferative activity in 72 unselected OETs. They comprised 16 benign cystadenomas, 18 borderline (low malignant potential) tumors, and 38 carcinomas (OECs). These patients had no known family history of breast and/or ovarian cancer. BRCA1 and the cell proliferation marker, MIB-1, expressions in fixed tissue were investigated in all 72 cases by immunohistochemistry (IHC). BRCA1 mRNA in fresh frozen tissue samples from 20 of these cases was measured by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS: The average percentage of BRCA1-positive cells was 5.6% in cystadenomas, 29.7% in borderline tumors, and 6.6% in OECs. The average decreased steadily with increasing grade of OECs: grade 1 (21.4%), grade 2 (1.1%), and grade 3 (0%). The average percentage of MIB-1-positive cells increased steadily from cystadenomas (7.5%) to borderline tumors (22.6%) to carcinomas (41.2%). BRCA1 expression was highly correlated with MIB-1 expression in cystadenomas and borderline tumors. Six of seven OECs negative for BRCA1 by IHC showed low levels of BRCA1 mRNA by RT-PCR. CONCLUSIONS: BRCA1 expression paralleled cell proliferation in benign and borderline OETs, but not in OECs. Sporadic OECs showed significantly reduced levels, rather than complete loss, of BRCA1 expression. The reduction was closely related to tumor grade. Reduction of BRCA1 expression may be of etiologic significance in the occurrence and progression of sporadic ovarian cancer.

Antigens, Nuclear↗

PubMed2000

Decreased luteinizing hormone receptor mRNA expression in human ovarian epithelial cancer.

OBJECTIVES: The objective of this study was to examine the distribution and cellular localization of luteinizing hormone receptor (LHR) in ovarian epithelial tumors (OETs) and their presumed precursor lesions-ovarian epithelial inclusions (OEIs). The clinicopathologic correlation of the receptor expression in OET was also examined. METHODS: Fifteen microdissected samples of ovarian surface epithelium (OSE), 20 OEIs from benign ovaries, and 141 OETs, including 48 cystadenomas, 33 borderline tumors, 60 carcinomas, and 5 metastatic cancers, were examined for LHR expression by using reverse transcription polymerase chain reaction and in situ hybridization. LHR expression in tumor epithelium and tumor stroma was analyzed separately. The clinicopathologic correlation data were analyzed by standard analysis of variance and contingency table methods. RESULTS: LHR expression was identified in the majority of OSE and OEI samples. In OETs, LHR positivity was found in the epithelial cells in 27% of cases and in the stromal compartment in 37% of cases. LHR-positive stromal cells were mainly luteinized cells. Within the tumor epithelium, LHR expression was detected in 42% of benign, 24% of borderline, and 17% of malignant OETs. LHR expression in tumor stroma showed a similar trend of reduction from benign to malignant OETs. Within the 17 carcinomas, LHR was expressed in the epithelium in 47% of grade 1, 12% of grade 2, and only 5% of grade 3 cancers. The mean age of the LHR-positive group was younger than that of the receptor-negative patients. Compared with mucinous and other types of OETs, serous OETs showed higher LHR expression in the epithelium. Compared with the OETs removed in the different menstrual phases, OETs in the secretory phase showed higher LHR in the tumor stroma than in the proliferative phase. No receptor mRNA was detected in the epithelium of five carcinomas metastatic to the ovary. LHR transcription splicing variants from a single previous report were confirmed in this study. CONCLUSIONS: Malignant OETs have significant reduction of LHR expression compared with precursor lesions and benign and borderline OETs. LHR expression shows a steady decline from low-grade to high-grade ovarian cancer. The presence of LHR receptor in tumor epithelium suggests that luteinizing hormone in serum may have direct influence on tumor growth, whereas the receptor in tumor stroma may be indicative of a paracrine function of LH in the development of OETs.

Adolescent↗

PubMed2000

Apoptosis may be an early event of progestin therapy for endometrial hyperplasia.

OBJECTIVE: The aim of this study was to investigate the role of apoptosis during progestin therapy for the treatment of endometrial hyperplasia. METHODS: Pre- and posttreatment paraffin-embedded endometrial tissue samples from 19 women with endometrial hyperplasia were examined for changes in glandular cellularity and apoptotic activity related to the administration of progestins. Twelve patients were successfully treated with progestin therapy and 7 patients failed treatment. Glandular cellularity was assessed based on calculating the average number of cells per gland obtained on histologic examination of hematoxylin and eosin stained tissue sections. Apoptotic activity was assessed on the same tissue sections by counting the average number of apoptotic cells per 10 high power fields (hpf) using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. The effects of progesterone on apoptotic activity in a low-grade endometrial adenocarcinoma cell line (Ishikawa cells) was also examined using an ELISA cell death detection kit. RESULTS: Glandular cellularity significantly decreased with progestin therapy in both treatment outcome groups. The reduction in cells per gland was significantly greater in the group of successfully treated cases compared to the treatment failures (P = 0.005). However, within the successfully treated group, in situ detection of apoptotic cells using the TUNEL assay showed no statistical difference between pre- and posttreatment endometrial samples. Interestingly, a significant decrease in apoptosis was found in posttreatment samples of the group with persistent hyperplasia. The average number of apoptotic cells detected in 10 hpf was reduced from 7.9 prior to treatment to 3.1 after progestin therapy (P = 0.03). In the progesterone-treated Ishikawa cell line, an increase in apoptotic activity started at 24 h, reached a peak at 48 h, and continued up to 72 h of hormone treatment. At 48 h, apoptotic activity was 42.6% greater than in the untreated control (P = 0.04). By 72 h of progesterone treatment, apoptosis was 37.2% greater in the treated cells compared to the noninoculated cells (P = 0.04). CONCLUSIONS: Progestin-induced apoptosis may occur during the early period of treatment for endometrial hyperplasia. Compared to the fully responsive group, persistent endometrial hyperplasia may have intrinsically different molecular mechanisms in response to progestin therapy.

Adult↗

PubMed2000

Interleukin-8 alters glomerular heparan sulfate glycosaminoglycan chain size and charge in rats.

We have previously shown that the in vivo infusion of interleukin-8 (IL8) in rats causes albuminuria and an increased catabolism of the heparan sulfate (HS) glycosaminoglycans (GAG). The purpose of this study was to characterize further the in vivo effect of IL8 on rat HSGAG. The left renal artery of male rats was continuously infused with IL8 (750 ng/ml, 4 rats) or 1% bovine serum albumin (3 rats) using an osmotic pump. On the 5th day of infusion, 35sulfate (1.0 mCi/100 g) was given intraperitoneally and the rat was killed 8 h later. Glomerular HSGAG was isolated and its size and charge was determined by liquid chromatography. The HSGAG 35sulfate uptake was higher in IL8-treated rats than controls (387+/-138 vs. 246+/-15 cpm/1,000 glomeruli, mean +/- SD, P<0.05). No differences in HSGAG size were observed between IL8-treated and control animals. However, after ion exchange chromatography, there was a shift to the left in the elution profile of IL8-treated rats, demonstrating the presence of chains with decreased negative charge. IL8 infusion into rats results in a decreased total negative charge of the HSGAG. Because IL8 has been found in the serum of some patients with minimal lesion nephrotic syndrome, this finding may explain, at least in part, the reported reduced glomerular charge barrier observed in these patients.

Animals↗

PubMed2000

Intracorporeal lithotripsy. Update on technology.

The number and variety of devices currently available for endoscopic lithotripsy reflect the reality that no single device is ideal in all situations. Although the search for the universal lithotriptor continues, the urologist must consider several factors if faced with the decision of which device to purchase. Perhaps foremost among these factors is the clinical situation with which one commonly deals. For example, although the smaller, flexible probes such as EHL or laser demonstrate considerable utility if used ureteroscopically, the larger stone burden associated with today's percutaneous nephrolithotripsy population often is treated more efficiently with one of the mechanical devices employing a larger, rigid probe, such as ultrasound or the Lithoclast. Similarly, the type and size of endoscopic equipment at one's disposal have a significant impact on which device to purchase or use. There are physical constraints affecting which device may or may not be used, rigid versus flexible endoscope, working channel caliber, and offset versus end-on-port. The skill and experience of the surgeon is also a factor of obvious importance, particularly if one is using a modality with a relatively narrow margin of safety such as EHL. Likewise, the training and experience of nursing personnel is a factor, especially regarding the use of lasers, which require certified personnel who are well versed in laser safety. Finally, in today's environment one must carefully evaluate cost in terms of not only initial capital outlay but also ongoing charges for disposable and maintenance items. Thus, the decision of which device to purchase is complex and requires careful evaluation of all of the previously noted variables. Likewise, if one is fortunate enough to have more than one device available, the decision of which lithotriptor to employ requires a similar decision based on sound surgical judgment.

Equipment Design↗

PubMed2000

Indomethacin induces apoptosis and inhibits proliferation in chronic myeloid leukemia cells.

A nonsteroidal anti-inflammatory drug (NSAID)--indomethacin (IN), was found to induce apoptosis and inhibit proliferation of K562 cells and primary culture bone marrow cells from six chronic myelogenous leukemia (CML) patients. IN induced cells apoptosis and inhibited cells proliferation in a dose-and time-dependent manner, the optimum IN concentration and incubation time for eliciting these effects were 400 micromol/l and 72 h, respectively. A synergic effect on Vp-16 (2.5 microg/ml) induced apoptosis was observed when combined with 100 micromol/l IN in K562 cells. RT-PCR results showed that IN down-regulated Bcl-2 mRNA expression, and did not change Bax mRNA expression; Western blot results confirmed that IN inhibited Bcl-2 protein expression, no influence was found on the translative level of bax protein. Our study indicate that IN induce apoptosis of CML cells by down-regulating Bcl-2 expression partially, and there is a potential significance in the treatment of CML.

Adult↗

PubMed2000

Intended and stray radiofrequency electrical currents during resectoscopic surgery.

STUDY OBJECTIVE: To test the hypothesis that electrical burns of the genital tract and urethral strictures after hysteroscopic endometrial ablation and transurethral prostatectomy, respectively, are related to capacitive coupling and/or stray currents induced by intact and defective electrodes and/or resectoscopes. DESIGN: Basic in vitro measurements. SETTING: Laboratory. MATERIALS: Porcine muscle and liver, resectoscope, electrosurgical unit (ESU), and ESU analyzer. INTERVENTION: We measured electrical coagulation and cutting currents of rollerball and loop electrodes and the external sheath of the resectoscope from 80 to 200 W through a resistance load of 200 and 250 ohms, using intact electrodes and conditions simulating potential insulation defects along the shaft of the electrodes. MEASUREMENTS AND MAIN RESULTS: Approximately 20% to 25% of current was induced by capacitive coupling to the resectoscope sheath. Touching porcine muscle or liver with small areas of the sheath while the generator was activated resulted in superficial tissue burn. Surrounding large segments of the sheath with tissue did not result in visible burns, indicating that under normal conditions the sheath acts as a dispersive electrode. Defective insulation of distal segments of the electrodes resulted in 100% transfer of current to the sheath and caused extensive electrical burns of tissue in contact with the sheath. CONCLUSIONS: Capacitive coupled currents induced by intact resectoscopes and electrodes may cause thermal injury to surrounding tissue during prolonged resectoscopic surgery. Stray currents from defective insulation of the electrodes result in direct coupling of current to the telescope and sheath and cause extensive burns of surrounding tissues in contact with the sheath.

Animals↗

PubMed2000

Novel variable selection quantitative structure--property relationship approach based on the k-nearest-neighbor principle

A novel automated variable selection quantitative structure-activity relationship (QSAR) method, based on the kappa-nearest neighbor principle (kNN-QSAR) has been developed. The kNN-QSAR method explores formally the active analogue approach, which implies that similar compounds display similar profiles of pharmacological activities. The activity of each compound is predicted as the average activity of K most chemically similar compounds from the data set. The robustness of a QSAR model is characterized by the value of cross-validated R2 (q2) using the leave-one-out cross-validation method. The chemical structures are characterized by multiple topological descriptors such as molecular connectivity indices or atom pairs. The chemical similarity is evaluated by Euclidean distances between compounds in multidimensional descriptor space, and the optimal subset of descriptors is selected using simulated annealing as a stochastic optimization algorithm. The application of the kNN-QSAR method to 58 estrogen receptor ligands as well as to several other groups of pharmacologically active compounds yielded QSAR models with q2 values of 0.6 or higher. Due to its relative simplicity, high degree of automation, nonlinear nature, and computational efficiency, this method could be applied routinely to a large variety of experimental data sets.

Journal Article↗

PubMed2000

Simultaneous single-cell detection of two mutations for cystic fibrosis.

PURPOSE: A single-cell diagnosis procedure using polymerase chain reaction (PCR) technology was developed to simultaneously detect two cystic fibrosis (CF) mutations (DF-508, W1282X). METHODS: The reported test procedures made use of specific cell lines (lymphoblasts, fibroblasts) of known CF mutation status to determine the efficiency of signal generation and prevalence of allele dropout (ADO) during amplification. RESULTS: Using cells carrying the DF-508 mutation, the PCR signal efficiency for the affected homozygous, normal homozygous, and carrier heterozygote cell populations were 91%, 81%, and 92%, respectively. The total combined PCR efficiency was 87.7% and the ADO rate was 5.7%. For W1282X carrier heterozygote cells, the PCR signal efficiency was 82.0% and the ADO rate was 8.7%. CONCLUSIONS: Methods have been developed to detect two common mutations simultaneously for CF in single-cell assays. The high signal efficiencies and low ADO rates obtained in these tests allow those embryos from couples wishing to avert the transmission of this serious genetic disease to their offspring to be screened by preimplantation genetic diagnosis.

Cell Line↗