Randomized clinical trial comparing suture and mesh repair of umbilical hernia in adults (Br J Surg 2001;88:1321-3).
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Adult↗
Biomedical subjects
P Tsai
Publications and source records attributed to P Tsai.
Differential effect of buffer on the spin trapping of nitric oxide by iron chelates.
Nitric oxide synthase (NOS) generates nitric oxide (NO*) by the oxidation of l-arginine. Spin trapping in combination with electron paramagnetic resonance (EPR) spectroscopy using ferro-chelates is considered one of the best methods to detect NO* in real time and at its site of generation. The spin trapping of NO* from isolated NOS I oxidation of L-arginine by ferro-N-dithiocarboxysarcosine (Fe(DTCS)2) and ferro-N-methyl-d-glucamide dithiocarbamate (Fe(MGD)2) in different buffers was investigated. We detected NO-Fe(DTCS)2, a nitrosyl complex, resulting from the reaction of NO* and Fe(DTCS)2, in phosphate buffer. However, Hepes and Tris buffers did not allow formation of NO-Fe(DTCS)2. Instead, both of these buffers reacted with Fe2+, generating sparingly soluble complexes in the absence of molecular oxygen. Fe(DTCS)2 and Fe(MGD)2 were found to inhibit, to a small degree, NOS I activity with a greater effect observed with Fe(MGD)2. In contrast, Fe(MGD)2 was more efficient at spin trapping NO* from the lipopolysaccharide-activated macrophage cell line RAW264.7 than was Fe(DTCS)2. Data suggested that Fe(DTCS)2 and Fe(MGD)2 are efficient at spin trapping NO* but their maximal efficiency may be affected by experimental conditions.
Animals↗
Involvement of the perferryl complex of nitric oxide synthase in the catalysis of secondary free radical formation.
Neuronal nitric oxide synthase (NOS I) has been shown to generate nitric oxide (NO*) and superoxide (O(2)* during enzymatic cycling, and the ratio of each free radical is dependent upon the concentration of L-arginine. Using spin trapping and electron paramagnetic resonance spectroscopy, we detected alpha-hydroxyethyl radical (CH(3)*CHOH), produced during the NOS I metabolism of ethanol (EtOH). The generation of CH(3)*CHOH by NOS I was found to be Ca(2+)/calmodulin dependent. Superoxide dismutase prevented CH(3)*CHOH formation in the absence of L-arginine. However, in the presence of L-arginine, the production of CH(3)*CHOH was independent of O(2)* but dependent upon the concentration of L-arginine. Formation of CH(3)*CHOH was inhibited by substituting D-arginine for L-arginine, or inclusion of the NOS inhibitors N(G)-nitro-L-arginine methyl ester, N(G)-monomethyl-L-arginine and the heme blocker, sodium cyanide. The addition of potassium hydrogen persulfate to NOS I, generating the perferryl complex (NOS-[Fe(5+)=O](3+)) in the absence of oxygen and Ca(2+)/calmodulin, and EtOH resulted in the formation of CH(3)*CHOH. NOS I was found to produce the corresponding alpha-hydroxyalkyl radical from 1-propanol and 2-propanol, but not from 2-methyl-2-propanol. Data demonstrated that the perferryl complex of NOS I in the presence of L-arginine was responsible for catalyses of these secondary reactions.
Arginine↗
Long-term outcome of antireflux surgery in patients with Barrett's esophagus.
OBJECTIVE: To assess the long-term outcome of antireflux surgery in patients with Barrett's esophagus. SUMMARY BACKGROUND DATA: The prevalence of Barrett's esophagus is increasing, and its treatment is problematic. Antireflux surgery has the potential to stop reflux and induce a quiescent mucosa. Its long-term outcome, however, has recently been challenged with reports of poor control of reflux and the inability to prevent progression to cancer. METHODS: The outcome of antireflux surgery was studied in 97 patients with Barrett's esophagus. Follow-up was complete in 88% (85/97) at a median of 5 years. Fifty-nine had long-segment and 26 short-segment Barrett's. Patients with intestinal metaplasia of the cardia were excluded. Fifty patients underwent a laparoscopic procedure, 20 a transthoracic procedure, and 3 abdominal Nissen operations. Nine had a Collis-Belsey procedure and three had other partial wraps. Outcome measures included relief of reflux symptoms (all), patients' perception of the result (all), upper endoscopy and histology (n = 79), and postoperative 24-hour pH monitoring (n = 21). RESULTS: At a median follow-up of 5 years, reflux symptoms were absent in 67 of 85 patients (79%). Eighteen (20%) developed recurrent symptoms; four had returned to taking daily acid-suppression medication. Seven patients underwent a secondary repair and were asymptomatic, increasing the eventual successful outcome to 87%. Recurrent symptoms were most common in patients undergoing Collis-Belsey (33%) and laparoscopic Nissen (26%) procedures and least common after a transthoracic Nissen operation (5%). The results of postoperative 24-hour pH monitoring were normal in 17 of 21 (81%). Recurrent hiatal hernias were detected in 17 of 79 patients studied; 6 were asymptomatic. Seventy-seven percent of the patients considered themselves cured, 22% considered their condition to be improved, and 97% were satisfied. Low-grade dysplasia regressed to nondysplastic Barrett's in 7 of 16 (44%), and intestinal metaplasia regressed to cardiac mucosa in 9 of 63 (14%). Low-grade dysplasia developed in 4 of 63 (6%) patients. No patient developed high-grade dysplasia or cancer in 410 patient-years of follow-up. CONCLUSIONS: After antireflux surgery, most patients with Barrett's enjoy long-lasting relief of reflux symptoms, and nearly all patients consider themselves cured or improved. Mild symptoms recur in one fifth. Importantly, dysplasia regressed in nearly half of the patients in whom it was present before surgery, intestinal metaplasia disappeared in 14% of patients, and high-grade dysplasia and adenocarcinoma were prevented in all.
Adolescent↗
Screening for and identification of novel agents directed at renal cell carcinoma.
We were interested in identifying novel agents for renal cell carcinoma (RCC) by screening for activities that model renal tumor biology. Searching for relative renal cell sensitivity and leukemia insensitivity among cytotoxicity profiles in the NCI Drug Screen database, we identified 16 potential agents with renal selectivity. We evaluated the agents in 10 RCC cell lines (of primary and metastatic origin) isolated from 5 patients. The 50% inhibitory concentrations (IC50) in these cell lines ranged from 0.019 +/- 0.013 to 11.4 +/- 0.55 microM and were comparable with values obtained with renal cell lines in the NCI Drug Screen panel. Because RCC are slowly growing tumors, we evaluated the compounds on rapidly (27% S phase) or slowly (6% S phase) growing cells. In contrast to doxorubicin, where cytotoxicity was restricted to rapidly proliferating cells, three compounds (NSC 280074, 281613, and 281817) were more cytotoxic in slowly proliferating cells. NSC 72151 and 268965 were equitoxic for both populations. NSC 94889, 638850, and 630938 were more cytotoxic in rapidly growing cells. In in vitro time exposure studies, four compounds, NSC 268965, 280074, 281613, and 281817, were maximally cytotoxic with as little as 3 h exposure time. From an analysis comparing the p53 genotype of the 60 cell lines of the National Cancer Institute (NCI) Drug Screen with the cytotoxicity profiles for the 16 putative renal compounds, 13 compounds were classified as likely to be indifferent to p53 status. We also developed a panel specificity detection method for the NCI Drug Screen database to evaluate the prevalence of renal sensitive compounds. Of the 16 studied compounds, 14 were among those identified as renal sensitive by the statistical analysis. Lastly, we found reduced tumor growth in mice with established renal human tumor xenografts after treatment with two of the renal active compounds. These studies describe compounds with potential renal activity that are candidates for preclinical development for renal cell carcinoma.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
A one-step synthesis of 2-(2-Pyridyl)-3H-indol-3-one N-oxide: is it an efficient spin trap for hydroxyl radical?
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Electron Spin Resonance Spectroscopy↗
Spin trapping of nitric oxide by ferro-chelates: kinetic and in vivo pharmacokinetic studies.
Biologically generated nitric oxide appears to play a pivotal role in the control of a diverse series of physiologic functions. Iron-chelates and low-frequency EPR spectroscopy have been used to verify in vivo production of nitric oxide. The interpretation of in vivo identification of nitric oxide localized at the site of evolution in real time is complicated by the varied kinetics of secretion. The quantitative efficiency of the spectroscopic measurement, so important in understanding the physiology of nitric oxide, remains elusive. The development of a more stable iron-chelate will help better define nitric oxide physiology. In this report, we present data comparing the commonly used ferro-di(N-methyl-D-glucamine-dithiocarbamate) (Fe2+(MGD)2) and the novel chelate ferro-di(N-(dithiocarboxy)sarcosine) (Fe2+(DTCS)2) quantifying the in vitro and in vivo stability of the corresponding spin trapped adducts, NO-Fe(MGD)2 and NO-Fe(DTCS)2. Finally, very low frequency EPR spectroscopy has been used to evaluate the pharmacokinetics of NO-Fe(MGD)2 and NO-Fe(DTCS)2 in mice in real time.
Drug Stability↗
Increased renal and vascular cytosolic phospholipase A2 activity in rats with cirrhosis and ascites.
Indirect evidence suggests that the renal and vascular production of prostaglandins is increased in cirrhosis with ascites. However, the activity of the enzymes regulating the prostaglandin pathway has not been investigated in cirrhosis. The aim of the current study was to determine the activity of phospholipase A2 (PLA2), the key enzyme in the regulation of prostaglandin synthesis, in kidney and vascular tissue obtained from rats with carbon tetrachloride-induced cirrhosis and ascites (n = 9) and control rats (n = 6). PLA2 activity was assayed in vitro using [14C]arachidonyl-phosphatidylcholine (PC) and [14C]arachidonyl-phosphatidylethanolamine (PE) as substrates in the presence of Ca2+. Kidneys from cirrhotic rats had significantly higher PLA2 activity compared with control rats, with both PC and PE (35 +/- 5 and 40 +/- 6 vs. 21 +/- 2 and 26 +/- 3 pmol/mg/min, respectively; P < .05 for both). PLA2 activity was increased in the renal cortex as well as in the renal medulla. Fractionation of the kidney extracts by Mono-Q anion-exchange chromatography showed that the elution position of PLA2 activity corresponded to the cytosolic PLA2 isoform (cPLA2). Increased amounts of cPLA2 protein were found in kidney extracts immunoblotted with an anti-cPLA2 antibody However, reverse-transcriptase polymerase chain reaction (RT-PCR) analysis did not detect any difference in cPLA2 mRNA. PLA2 activity was also higher in aortic tissue from cirrhotic rats than in controls (PC 38 +/- 5 vs. 26 +/- 1 and PE 66 +/- 8 vs. 41 +/- 3 pmol/mg/min; P < .05 for both). Incubation of renal and aortic extracts from cirrhotic rats with anti-cPLA2 antibody reduced PLA2 activity by 64% and 88%, respectively. In conclusion, PLA2 activity is increased in kidneys and vascular tissue from cirrhotic rats with ascites. This can be accounted for by an induction of cPLA2, which would mediate, at least in part, the increased renal and vascular production of prostaglandins in cirrhosis.
Animals↗
Overexpression of transfected human ribonucleotide reductase M2 subunit in human cancer cells enhances their invasive potential.
The ribonucleotide reductase (RR) gene has been associated with malignant transformation and metastatic potential. In this report, the significance of the expression of RR mRNA and enzymatic activity to the invasive potential was examined by Boyden chamber invasion assay. Our results suggest that overexpression of RR M2 mRNA and RR enzymatic activity correlates to an increase in cell invasive potential. The drug-induced HURs clone expressed a higher level RR M2 mRNA and enzyme activity which contributes significantly to the 3-fold increase in invasive potential of the cells observed relative to the KB wild-type control. On the contrary, the HUr revertant clone decreased the RR M2 mRNA level and enzymatic activity, concomitantly decreasing their invasive potential. This phenomenon is most likely due to the return of RR to levels comparable to that of the KB wild-type cells. To confirm that this observation was not of a drug-resistance phenotype associated with multiple gene alterations, the panel of RR transfectants (M1-D transfected M1 subunit cDNA, M2-D transfected M2 subunit cDNA, X-D transfected M1/M2 cDNA) characterized in a previous study were also tested in the invasion assay. The M2-D clone expressed 6-fold higher RR M2 mRNA and RR activity and also demonstrated 6-fold higher invasive potential in vitro than either the parental or vector only transfected cell line (KB-V). The X-D clone demonstrated 3-fold higher M2 mRNA expression and revealed 4-fold higher invasive potential than control cells. The M1-D clone, in contrast, expressed a baseline level of RR M2 mRNA and higher M1 mRNA. In contrast to the X-D and M2-D cells, the invasive potential of M1-D reached an even lower level in the invasive assay than the control. These results, therefore, suggest that RR M2 overexpression plays an important role in a tumor's invasiveness.
Carcinoma↗
Androgens and masculinization of genitalia in the spotted hyaena (Crocuta crocuta). 1. Urogenital morphology and placental androgen production during fetal life.
According to common understanding of sexual differentiation, the formation and development of a penile clitoris in female spotted hyaenas requires the presence of naturally circulating androgens during fetal life. The purpose of the present study was to determine potential source(s) of such fetal androgens by investigating the timing of urogenital development and placental production of androgen during early and mid-gestation. Fetuses determined to be female by molecular techniques (lack of SRY gene) at days 33 and 48 of gestation had undifferentiated gonads, but the clitoris was already 'masculinized' and was generally similar to the phallus of a 50-day-old male fetus. Wolffian and Müllerian ducts terminated at the urogenital sinus in both sexes and a urethra was present along the entire length of the clitoris and penis. The adrenal gland was large and histologically differentiated at 33 days. Steroid gradients across the uterus (a drop in delta 4-androstenedione, with increases in oestrogen and androgen), and high androstenedione in ovarian veins indicated that ovarian androstenedione was metabolized and secreted as testosterone by the placenta throughout gestation. In vitro, whole or homogenized placentae at days 48 and 58 of gestation (110 days total) metabolized radiolabelled androstenedione into testosterone and oestradiol; the specific enzymatic activity of early placental tissues was higher than at later stages. A human placental homogenate had higher aromatase activity but did not produce testosterone unless aromatase was inhibited. Infusion of labelled androstenedione into the uterine arteries of hyaenas demonstrated the conversion of this substrate into testosterone and oestradiol and their secretion into the fetal circulation. Evidently, androgen is produced by the placenta and secreted into the fetal circulation from early in pregnancy when masculinization is first evident, before differentiation of the fetal ovary.
Androgens↗
Logistic analysis of shovel and Carabelli's tooth traits in a Caucasoid population.
Caucasoid populations differ from Mongoloids by having a high prevalence of Carabelli's trait and a low prevalence of shovel trait. This study was conducted to investigate the association between the shovel and the Carabelli's traits in a Caucasoid population. The research design sought a Caucasoid population at Milwaukee of Wisconsin in United States. The Caucasoid group selected for study was the European descendant. The effects of sex and age on Carabelli's trait were controlled in this investigation, as was the association between tooth size and Carabelli's trait. Results show that males were more likely to have Carabelli's trait expressed on teeth than females. The buccolingual diameter of Carabelli's trait teeth was larger than that of teeth without the trait. After adjusting for sex, age, and tooth size, the existence of the shovel trait decreased the likelihood of having Carabelli's trait which shows an significant effect.
Asian People↗
P-element insertion alleles of essential genes on the third chromosome of Drosophila melanogaster: mutations affecting embryonic PNS development.
To identify novel genes and to isolate tagged mutations in known genes that are required for the development of the peripheral nervous system (PNS), we have screened a novel collection of 2460 strains carrying lethal or semilethal P element insertions on the third chromosome. Monoclonal antibody 22C10 was used as a marker to visualize the embryonic PNS. We identified 109 mutant strains that exhibited reproducible phenotypes in the PNS. Cytological and genetic analyses of these strains indicated that 87 mutations affect previously identified genes: tramtrack (n = 18 alleles), string (n = 15), cyclin A (n = 13), single-minded (n = 13), Delta (n = 9), neuralized (n = 4), pointed (n = 4), extra macrochaetae (n = 4), prospero (n = 3), tartan (n = 2), and pebble (n = 2). In addition, 13 mutations affect genes that we identified recently in a chemical mutagenesis screen designed to isolate similar mutants: hearty (n = 3), dorsotonals (n = 2), pavarotti (n = 2), sanpodo (n = 2), dalmatian (n = 1), missensed (n = 1), senseless (n = 1), and sticky ch1 (n = 1). The remaining nine mutations define seven novel complementation groups. The data presented here demonstrate that this collection of P elements will be useful for the identification and cloning of novel genes on the third chromosome, since >70% of mutations identified in the screen are caused by the insertion of a P element. A comparison between this screen and a chemical mutagenesis screen undertaken earlier highlights the complementarity of the two types of genetic screens.
Alleles↗
Digital chest radiography: effect of temporal subtraction images on detection accuracy.
PURPOSE: To improve early detection of disease in chest radiographs, the authors developed a digital processing technique that geometrically warps and subtracts a previous radiograph from a current radiograph to produce a temporal subtraction image. An observer test was performed to evaluate the effects of the temporal subtraction image technique on detection of interval change. MATERIALS AND METHODS: Fifty pairs of chest radiographs, including a baseline examination and a subsequent radiograph, were selected (25 cases in which potentially important new abnormalities had developed, and 25 in which there was no interval change). The baseline examination was chosen from multiple prior radiographs to minimize initial misregistration. By means of receiver operating characteristic (ROC) analysis, the ability of 11 observers to detect pathologic change when viewing the paired digitized baseline and subsequent radiographs was compared with their ability when viewing the same paired radiographs together with temporal subtraction images. Positive cases demonstrated focal new abnormalities that were greater than 1 cm in diameter. RESULTS: The mean area (Az) under the ROC curves increased from 0.89 without to 0.98 with the temporal subtraction images. When the paired digitized previous and current chest radiographs were viewed in conjunction with the temporal subtraction images, a significant improvement in detection of new abnormalities was achieved (P = .00004), whereas the mean interpretation time was reduced by 19.3% (from 52 to 42 seconds, including the time to record the score and to move to the next case) (P = .0019). CONCLUSION: The temporal subtraction technique can significantly improve sensitivity and specificity for detection of interval change in chest radiographs.
Humans↗
Comparison of vascular nitric oxide production and systemic hemodynamics in cirrhosis versus prehepatic portal hypertension in rats.
Nitric oxide (NO) is postulated to play a role in the pathogenesis of arterial vasodilation in chronic portal hypertension. This present study investigates the relationship between systemic hemodynamics and the vascular production of NO, as estimated by measuring cyclic guanosine monophosphate (cGMP) in aortic tissue in two models of chronic portal hypertension in the rat: the partial portal vein ligation (PVL) model and CCl4-induced cirrhosis. NOS was also examined by Western blotting in aortic and mesenteric vessels. Sham-operated rats and rats given phenobarbital were used as controls. PVL rats and rats with cirrhosis and ascites showed a typical pattern of a hyperdynamic circulatory state, when compared with their respective controls: mean arterial pressure; PVL: 113 +/- 2 versus 124 +/- 2, P < .01 and cirrhotics: 103 +/- 5 versus 130 +/- 4 mm Hg, P < .01. Cardiac index; PVL: 32 +/- 2 versus 26 +/- 1, P < .01 and cirrhotics: 51 +/- 3 versus 30 +/- 1 mL . min-1 . 100 gm-1, P < .0001. Systemic vascular resistance; PVL: 3.7 +/- 0.1 versus 4.9 +/- 0.2, P < .01 and cirrhotics: 2.1 +/- 0.2 versus 4.4 +/- 0.2 mm Hg . min-1 100 g-1, P < .0001. Aortic cGMP was markedly increased in cirrhotic rats with ascites (728 +/- 83 fmol/ mg protein) as compared with phenobarbital-treated controls (244 +/- 31 fmol/mg, P < .001). This increase was abolished by chronic administration of N(omega)-nitro-L-arginine methyl ester. By contrast, PVL rats had an aortic cGMP concentration similar to sham-operated controls (282 +/- 16 fmol/mg vs. 274 +/- 33 fmol/mg, P = not significant) and significantly lower than that found in cirrhotic rats with ascites. Expression of cirrhotic aortic endothelial nitric oxide synthase (eNOS) was increased but PVL aortic eNOS did not differ from that of controls, whereas the mesenteric eNOS was increased in both PVL and cirrhotic rats as compared with the controls. These results suggest that vascular NO production is higher in cirrhotic rats than in PVL rats. This increased production may contribute to the more marked abnormalities in systemic hemodynamics seen in experimental cirrhosis as compared with PVL.
Animals↗
Laparoscopic fundoplication 1 month prior to lung transplantation.
Upper midline laparotomy in the presence of pulmonary failure is often complicated by a prolonged period of mechanical ventilation postoperatively. We report the successful performance of laparoscopic fundoplication, without ventilatory support, in a woman with end stage pulmonary disease and resting hypercarbia, one month prior to lung transplantation.
Female↗
Upregulation of endothelial and neuronal constitutive nitric oxide synthase in pregnant rats.
Pregnancy is characterized by hemodynamic and body fluid alterations. Increased nitric oxide (NO) production has been suggested to play a role in the hemodynamic alterations of pregnancy and has also been reported to increase arginine vasopressin (AVP) release. We therefore hypothesized that gestation could increase both NO synthase (NOS) constitutive isoforms, neuronal NOS and endothelial NOS, and thereby contribute to the hyposmolality and peripheral arterial vasodilation of pregnancy, respectively. The present study was therefore undertaken to examine the constitutive NOS isoforms in aortas, mesenteric arteries, and hypothalami of pregnant rats on day 20 of gestation compared with age-matched nonpregnant rats. Plasma AVP was determined by radioimmunoassay and hypothalamic mRNA AVP by solution hybridization assay. Hypothalamic neuronal NOS was assessed by Northern blot and Western blot; endothelial NOS was assessed by Western blot in arteries and hypothalamus. The results demonstrated that 1) plasma AVP and hypothalamic AVP mRNA are increased in pregnant rats (n = 8), 2) neuronal NOS protein and mRNA are increased in hypothalamus of pregnant rats (n = 4), and 3) endothelial NOS expression, as assessed by Western blot analysis, is increased in both conductance (aorta) as well as resistance (mesenteric) arteries of pregnant rats (n = 4). We conclude that both of the constitutive NOS isoforms are increased in pregnant rats, suggesting that the peripheral arterial vasodilation and hyposmolality of pregnancy could be mediated by these isoforms.
Animals↗
Upregulation of endothelial constitutive NOS: a major role in the increased NO production in cirrhotic rats.
Nitric oxide (NO) is postulated to mediate the peripheral arterial vasodilation in cirrhosis. However, it is not known which isoform of the nitric oxide synthase (NOS) is involved in the increased production of NO. This study was therefore undertaken to examine the expression of the NOS isoforms in arteries of cirrhotic rats compared with controls. Cirrhosis was induced by CCl4, and vessels were harvested for immunoblots using antibodies against inducible NOS (iNOS) and endothelial constitutive NOS (ecNOS). Endothelial cells were used as controls for ecNOS, and vascular smooth muscle cells treated with lipopolysaccharide or septic rats were used for iNOS controls. The results demonstrated an upregulation of ecNOS in both the aortas and mesenteric arteries of cirrhotic compared with control rats. Chronic inhibition of NOS decreased ecNOS in cirrhotic vessels. Although iNOS mRNA was found by reverse transcription-polymerase chain reaction in arteries of cirrhotic rats, iNOS protein was not detectable by immunoblotting compared with septic rats, suggesting a low vascular level of this isoform. In conclusion, the ecNOS seems to play a major role in the increased NO production in cirrhotic rats, whereas the role of iNOS remains elusive.
Animals↗
Foundational issues concerning the analysis of censored data.
The common approach to analyzing censored data utilizes "competing risk" models; a class of distribution is first chosen and then the sufficient statistics are identified! An "operational Bayesian" approach (Barlow 1993) for analyzing censored data would require a somewhat different methodology. In this approach, we first determine potentially observable parameters of interest. We then determine the data summaries (sufficient statistics) for these parameters. Tsai (1994) suggests that the observed sample frequency is sufficient for predicting the population frequency. Invariant probability measures (likelihoods), conditional on the parameters of interest, are then derived based on the principle of sufficiency and the principle of insufficient reason.
Bayes Theorem↗