Dexfenfluramine as a mitogen signal via the formation of superoxide anion.
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Antioxidants↗
Biomedical subjects
S L Lee
Publications and source records attributed to S L Lee.
H(2)O(2) signals 5-HT-induced ERK MAP kinase activation and mitogenesis of smooth muscle cells.
Our previous studies have shown that 5-hydroxytryptamine (5-HT) induces cellular hyperplasia/hypertrophy through protein tyrosine phosphorylation, rapid formation of superoxide (O(2)(-)), and extracellular signal-regulated kinase (ERK)1/ERK2 mitogen-activated protein (MAP) kinase activation. Intracellularly released O(2)(-) is rapidly dismuted by superoxide dismutase (SOD) to H(2)O(2), another possible cellular growth mediator. In the present study, we assessed whether H(2)O(2) participates in 5-HT-induced mitogenic signaling. Inactivation of cellular Cu/Zn SOD by copper-chelating agents inhibited 5-HT-induced DNA synthesis of bovine pulmonary artery smooth muscle cells (BPASMCs). Infection of BPASMCs with an adenovirus containing catalase inhibited both ERK1/ERK2 MAP kinase activation and DNA synthesis induced by 5-HT. Although we could not find evidence of p38 MAP kinase activation by 5-HT, SB-203580 and SB-202190, reported inhibitors of p38 MAP kinase, inhibited the 5-HT-induced growth of BPASMCs. However, these inhibitors also inhibited 5-HT-induced O(2)(-) release. Thus quenching of O(2)(-) may be their mechanism for inhibition of cellular growth unrelated to p38 MAP kinase inhibition. These data indicate that generation of O(2)(-) in BPASMCs in response to 5-HT is followed by an increase in intracellular H(2)O(2) that mediates 5-HT-induced mitogenesis through activation of ERK1/ERK2 but not of p38 MAP kinase.
Animals↗
Evaluation of intra-abdominal pressure after laparoscopic and open gastric bypass.
BACKGROUND: Increased intra-abdominal pressure (IAP) postoperatively can adversely affect cardiovascular, pulmonary, and renal function. In this prospective, randomized trial, we compared the IAP in morbidly obese patients after laparoscopic and open gastric bypass (GBP) surgery. METHODS: 64 patients with a body mass index of 40 to 60 kg/m2 were randomized to undergo laparoscopic or open GBP. IAPs were obtained at baseline (after induction of anesthesia), immediately after the operation, and on post-operative day (POD) 1, 2, and 3. Intraoperative and postoperative fluid requirements, urine output, and creatinine clearance were recorded. RESULTS: Demographics of the two groups were similar. IAP increased from baseline immediately after laparoscopic and open GBP (p < 0.05). IAP returned to baseline by POD 2 after laparoscopic GBP but remained elevated through POD 3 after open GBP. In fact, IAP was lower after laparoscopic GBP than after open GBP on POD 1, 2 and 3 (p < 0.05). The amount of intraoperative IV fluid was similar between groups, but laparoscopic GBP required less IV fluid and facilitated higher urine output postoperatively than open GBP. There was no significant difference in creatinine clearance between groups. CONCLUSIONS: Laparoscopic GBP resulted in significantly lower IAP, less postoperative fluid required, and greater postoperative urine output than open GBP.
Abdomen↗
Effect of preproTRH antisense on thyrotropin-releasing hormone synthesis and viability of cultured rat diencephalic neurons.
To investigate a possible neurotropic role for thyrotropin-releasing hormone (TRH) in the central nervous system, we used recombinant antisense TRH adenovirus (TRHav) to "knock out" TRH in cultured 17-d fetal rat diencephalon. The morphology along with beta-galactosidase (beta-gal) enzyme histochemistry (X-gal staining) and TRH content (femtomoles/well) were used to measure the effect of antisense TRH virus. Control adenovirus mediated beta-gal transfection efficiency was nearly 85%, as shown by positive X-gal staining, and was without effect on cell morphology, TRH content, or the normal response to glucocorticoid (dexamethasone) exposure with enhanced TRH expression. A significant 90% decline in TRH content as well as changes in neuronal morphology (shrunken cell bodies and short dendrites) were observed after 14 but not 7 d following TRHav treatment. The addition of synthetic TRH peptide at 2.5 microM along with TRHav, but not dexamethasone, partly prevented the morphologic changes. No morphologic changes were seen in wild-type AtT20 cells, a pituitary cell line that does not produce TRH. To investigate whether neuronal death from loss of proTRH was owing to apoptosis, neuronal DNA change by means of fluorescent dye H-33342 staining, TUNEL staining, and DNA laddering analysis was examined. Eighty to 90% positive H-33342 and TUNEL staining as well as a 180- to 200-bp DNA fragment on DNA laddering analysis were found as compared to control. These results indicate that proTRH gene expression prevents neuronal apoptosis and may play a role in neuronal development and function.
Adenoviridae↗
Differential regulation of the TRH gene promoter by triiodothyronine and dexamethasone in pancreatic islets.
TRH was initially found in the hypothalamus and regulates TSH secretion. TRH is also produced by insulin-containing beta-cells. Endogenous TRH positively regulates glucagon secretion and attenuates pancreatic exocrine secretion. We have previously shown that triiodothyronine (T(3)) down-regulates pre-pro-TRH gene expression in vivo and in vitro. The present study was designed to determine the initial impact of T(3) on rat TRH gene promoter and to compare this effect with that of dexamethasone (Dex). Primary islet cells and neoplastic cells (HIT T-15 and RIN m5F) were transiently transfected with fragments of the 5'-flanking sequence of TRH fused to the luciferase reporter gene. The persistence of high TRH concentrations in fetal islets in culture, probably due to transactivating factors, allowed us to explore how T(3) and Dex regulate the TRH promoter activity in transfected cells and whether the hormone effect is dependent on the cell type considered. TRH gene promoter activity is inhibited by T(3) in primary but not neoplastic cells and stimulated by Dex in both primary and neoplastic cells of islets. These findings validate previous in vivo and in vitro studies and indicate the transcriptional impact of these hormones on TRH gene expression in the pancreatic islets.
Animals↗
[Stressors and coping behaviors of mothers with child receiving open heart surgery].
The purposes of this longitudinal study were to (1) explore the stressors and coping behaviors of mothers having a child with congenital heart disease undergoing open heart surgery, and (2) understand the changes over time in these stressors and coping behaviors as the treatment process progressed. The field method was used to collect data, which was transcribed as a narrative verbal process recording. The records were then analyzed by content analysis. This study had ten subjects chosen by purposive sampling. The results showed that stressors on the mother whose child was undergoing open heart surgery could be inductively categorized as follows: the ill child, the treatment, and the mother herself. The coping behaviors consisted of cognitive behavior, emotional response, and management. At different stages of the 5045 behavior units were coded. There was a significant difference in the contribution of the stressors and coping behaviors at different stages of the treatment process. The findings can help nurses better understand the experience and provide some directions to assist mothers with child undergoing open heart surgery.
Adaptation, Psychological↗
Ultrasonography of the lower leg: technique, anatomy and pathologic conditions.
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Achilles Tendon↗
Activation of hepatocyte growth factor and urokinase/plasminogen activator by matriptase, an epithelial membrane serine protease.
Matriptase is an epithelial-derived, integral membrane serine protease. The enzyme was initially isolated from human breast cancer cells and has been implicated in breast cancer invasion and metastasis. In the current study, using active matriptase isolated from human milk, we demonstrate that matriptase is able to cleave various synthetic substrates with arginine or lysine as their P1 sites and prefers small side chain amino acids, such as Ala and Gly, at P2 sites. For the most reactive substrates, N-tert-butoxycarbonyl (N-t-Boc)-gamma-benzyl-Glu-Ala-Arg-7-amino-4-methylcoumarin (AMC) and N-t-Boc-Gln-Ala-Arg-AMC, the K(m) values were determined to be 3. 81 and 4.89 microm, respectively. We further demonstrated that matriptase can convert hepatocyte growth factor/scattering factor to its active form, which can induce scatter of Madin-Darby canine kidney epithelial cells and can activate c-Met tyrosine phosphorylation in A549 human lung carcinoma cells. In addition, we noted that matriptase can activate urokinase plasminogen activator but has no affect on plasminogen. These results suggest that matriptase could act as an epithelial, upstream membrane activator to recruit and activate stromal-derived downstream effectors important for extracellular matrix degradation and epithelial migration, two major events of tissue remodeling, cancer invasion, and metastasis.
Animals↗
Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice.
Aged humans sustain a high rate of epithelial cancers such as carcinomas of the breast and colon, whereas mice carrying common tumour suppressor gene mutations typically develop soft tissue sarcomas and lymphomas. Among the many factors that may contribute to this species variance are differences in telomere length and regulation. Telomeres comprise the nucleoprotein complexes that cap the ends of eukaryotic chromosomes and are maintained by the reverse transcriptase, telomerase. In human cells, insufficient levels of telomerase lead to telomere attrition with cell division in culture and possibly with ageing and tumorigenesis in vivo. In contrast, critical reduction in telomere length is not observed in the mouse owing to promiscuous telomerase expression and long telomeres. Here we provide evidence that telomere attrition in ageing telomerase-deficient p53 mutant mice promotes the development of epithelial cancers by a process of fusion-bridge breakage that leads to the formation of complex non-reciprocal translocations--a classical cytogenetic feature of human carcinomas. Our data suggest a model in which telomere dysfunction brought about by continual epithelial renewal during life generates the massive ploidy changes associated with the development of epithelial cancers.
Adenocarcinoma↗
Reconstruction from small-angle neutron scattering measurements of the real space magnetic field distribution in the mixed state of Sr2RuO4.
We have measured the diffracted neutron scattering intensities from the square magnetic flux lattice in the perovskite superconductor Sr2RuO4, which is thought to exhibit p-wave pairing with a two-component order parameter. The relative intensities of different flux lattice Bragg reflections over a wide range of field and temperature have been shown to be inconsistent with a single component Ginzburg-Landau theory but qualitatively agree with a two-component p-wave Ginzburg-Landau theory.
Journal Article↗
Preliminary study of in vivo autofluorescence of nasopharyngeal carcinoma and normal tissue.
BACKGROUND AND OBJECTIVE: In nasopharyngeal cancer, conventional white light endoscopy does not provide adequate information to detect the flat/small lesion and identify the margin of observable tumor. In the present study, we evaluate the potential of light-induced fluorescence spectroscopic imaging for the localization of cancerous nasopharyngeal tissue. STUDY DESIGN/MATERIALS AND METHODS: We built a multiple channel spectrometer specifically for the investigation of fluorescence collected by a conventional endoscopic system. Nasopharyngeal fluorescence were measured in vivo from 27 subjects during the routine endoscopy. The biopsy specimens for histologic analysis were taken from the tissue sites where the fluorescence were measured. RESULTS: Two algorithms to discriminate the nasopharyngeal carcinoma from normal tissue were created based on the good correlation between the tissue autofluorescence and histologic diagnosis. For the two-wavelength algorithm, carcinoma can be differentiated from normal tissue with a sensitivity and specificity of 93% and 92%, respectively. For the three-wavelength algorithm with compensation of variation of blood content in tissue, a sensitivity of 98% and specificity of 95% were achieved. CONCLUSION: Fluorescence endoscopic imaging used with the algorithms developed in this report is an efficient method for detecting the nasopharyngeal carcinoma.
Algorithms↗
Serum CTX: a new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy.
Serum CrossLaps is a new assay for measuring carboxy-terminal collagen crosslinks (CTX) in serum. This measurement is reported to be more specific to bone resorption than other measurements. However, the utility of this and other markers in monitoring patients on antiresorptive therapy depends on how often changes anticipated with therapy exceed changes attributable to random variability. In a study where subjects received either placebo or pamidronate, we calculated the minimum significant change (MSC), that is, the change that was sufficiently large that it was unlikely to be due to spontaneous variability. We also examined the changes in markers of bone turnover in subjects treated with pamidronate (APD) (30 mg i.v. in 500 ml D5W over 4 hours) to see how often observed changes in turnover after treatment exceeded the MSC. The MSC for serum CTX was 30.2%, and was significantly (P < 0.05) lower than the MSC for urinary NTX (54.0%), and not significantly different from the MSC of urinary DPD (20.6%). Ninety percent of subjects treated with APD had a decline in serum CTX that exceeded the MSC, compared with 74% for bone-specific alkaline phophatase (BSAP), 57% for urinary N-telopeptide cross-links (NTX), and 48% for free deoxypyridinoline. Changes in serum CTX correlated reasonably well with changes in spine BMD after 2 years (r = 0.47), but this correlation did not quite reach statistical significance because of the small number of subjects. In conclusion, the serum CTX assay shows greater utility for assessing efficacy of antiresorptive treatment than some previously described markers.
Anti-Inflammatory Agents↗
Laparoscopic diagnosis and repair of pediatric femoral hernia. Initial experience of four cases.
Femoral hernias are often misdiagnosed and treated as inguinal hernias. Thus, laparoscopic groin exploration may be a valuable means of evaluating children with presumed recurrent inguinal hernias. This study describes the feasibility of laparoscopic groin exploration and femoral hernia repair in children. Four children (aged 2, 2, 3, and 17 years) with reported unilateral recurrent inguinal hernias underwent diagnostic laparoscopy via a 4-mm pediatric laparoscope. Contralateral defects were visualized in all four patients; there were three femoral hernias and one direct inguinal hernia. None of the contralateral defects had been suspected clinically. Of the seven femoral defects, five were repaired laparoscopically. One patulous defect was repaired by reapproximating the iliopubic tract to Cooper's ligament and overlaying a preperitoneal Teflon felt(R) patch. The other four defects were repaired using a Teflon felt(R) plug and preperitoneal patch. A total of three ports were required in each patient (umbilical, suprapubic, and one in between). Two femoral defects in one patient required open repair because a large lipoma prevented adequate visualization and diagnosis. The direct inguinal hernia was also repaired using the open technique. Laparoscopic groin exploration and femoral hernia repair in pediatric patients is safe and technically feasible. Its advantages, however, such as superior diagnostic ability and simultaneous bilateral tension-free repair, need to be validated with a larger study and longer follow-up.
Adolescent↗
Testicular damage after surgical groin exploration for elective herniorrhaphy.
BACKGROUND/PURPOSE: Controversy exists whether to explore the contralateral groin in boys during unilateral herniorrhaphy. Proponents claim there is minimal risk of injury to the cord structures and developing testicle with contralateral exploration. However, findings have shown testicular atrophy occurred in 1% to 2% of patients after herniorrhaphy, and vasal damage is possible after routine manipulation of the spermatic cord. This study investigated the effect of routine surgical exploration of the prepubertal groin on testicular development and future fertility. METHODS: Twenty-four prepubertal Wistar rats were divided equally into 2 groups. Group 1 (sham) rats underwent unilateral inguinoscrotal incision only. Group 2 (experimental) rats underwent unilateral inguinoscrotal exploration with manipulation of the cord structures as in human inguinal exploration. At maturation, the fertility and fecundity of the males were assessed. After mating, testes were examined for mass, volume, mean seminiferous tubule diameter (MSTD), and mean testicular biopsy score (MTBS). The vasa were examined for histological injury and vasal diameter. Statistical comparisons were made by paired t test and Mann-Whitney rank sum test. RESULTS: There was a difference between the volumes of the testes when comparing the operative and nonoperative side of the 2 groups (experimental, deltavol = -0.063+/-0.123; sham, deltavol = +0.067+/-0.137; P = .029). There also was a trend toward a smaller testicular mass when comparing the two sides (experimental, deltamass = -0.045+/-0.101; sham, Amass = +0.048+/-0.123; P = .057) but did not reach significance. The MSTD and MTBS were similar between the ipsilateral and contralateral testes in both groups. Likewise, the MSTD and MTBS were similar when comparing the 2 groups. All male rats in both groups were fertile. The number of offspring produced and the number of female rats impregnated were similar between the 2 groups. There was no histological evidence of vasal injury in any of the experimental spermatic cords. The vasal diameters were similar between the 2 groups. CONCLUSION: Surgical manipulation of the prepubertal spermatic cord imparts a small, but statistically significant morphological change in testicular size without a deleterious effect on testicular development, fertility, or fecundity.
Animals↗
Production and molar yield of 2-phenylethanol by Pichia fermentans L-5 as affected by some medium components.
In this study, the effects of carbon sources and various levels of sucrose (0-30%) yeast extract (0-1.25%) and phenylalanine (0-0.2%) on the production of 2-phenylethanol by Pichia fermentans L-5 were investigated. Results revealed that among the 11 carbon sources tested, glycerol and sucrose were suitable carbon sources for P. fermentans L-5 resulting in production of higher amounts of 2-phenylethanol. In the medium that contained 18% sucrose, P. fermentans L-5 produced the highest amount of 2-phenylethanol, 283.4 mg/l with a molar yield of 0.77, was noted among the various levels of sucrose tested. Increasing the amount of phenylalanine added to the culture medium to 1.0% resulted in increased production of phenylethanol. Enhanced production of 2-phenylethanol, 453.1 mg/l by P. fermentans L-5 with a molar yield of 0.71 for phenylethanol was obtained in the medium containing 18% sucrose, 0.25% yeast extract and 0.1% phenylalanine after 16 h of fermentation.
Journal Article↗
Mating system parameters of Dryobalanops aromatica Gaertn. f. (Dipterocarpaceae) in three different forest types and a seed orchard.
The mating system of Dryobalanops aromatica in three different forest types and a seed orchard was quantified by allozyme analysis of progeny arrays using a mixed-mating model. The primary forest (Bukit Sai) had the highest multilocus outcrossing rate (tm=0.923 +/- 0.035), followed by logged forest (Lesong; tm=0.766 +/- 0.056) and artificial forest (FRIM; tm=0.661 +/- 0.066) with seed orchard showing the lowest (Tampin; tm=0.551 +/- 0.095). Deviations from the mixed mating model were evident from differences in pollen and ovule allele frequencies, and heterogeneity of pollen pools in all three different forest types and the seed orchard. A high rate of outcrossing in primary forest (tm=0.92) may indicate that the species is self-incompatible, but a lower value in the seed orchard (tm=0.55) might suggest further that the self-incompatibility system is weak. The outcrossing rate was greater in the primary forest (tm=0.92) than in logged forest (tm=0.77). It is argued that this might be a consequence of the lower density of flowering trees and alteration of pollinator foraging behaviour in logged forest. Higher values of correlated mating (rp) and biparental mating (tm - ts) in primary forest (0.08 and 0.39, respectively) in comparison with logged forest (0.03 and 0.11, respectively) demonstrate that logging activities might reduce the seeds produced through consanguineous mating. Compared with primary forest, it is argued that lower rates of outcrossing in artificial forest (tm=0.67) and seed orchard (tm=0. 55) might be attributed to lack of flowering synchrony and insufficient number of pollinators. The high level of correlated mating (rp=0.43) and biparental mating (tm - ts=0.12) in the seed orchard may further suggest that the seed orchard was established using related seed sources.
Crosses, Genetic↗
Estimation of gene flow in the tropical-rainforest tree Neobalanocarpus heimii (Dipterocarpaceae), inferred from paternity analysis.
Pollen flow and population genetic structure among 30 potentially flowering individuals of Neobalanocarpus heimii, a tropical emergent tree, were investigated in a lowland tropical rainforest of Malaysia using microsatellite polymorphism. The 248 offspring in the vicinity of five reproductive trees of the 30 potentially flowering trees were used in paternity analysis for pollen-flow study. Four primer pairs, developed in different species of dipterocarps, were adopted to detect microsatellite polymorphism. Based upon microsatellite polymorphism, pollen flow and seed migration were detected. Pollen-flow events of more than 400 m were observed directly, based on paternity analysis in the study plot. The estimated average mating distance of the five reproductive trees was 524 m. This result suggests that reproduction of this species is mediated by a long-distance pollinator. The haplotypes of some offspring were not compatible with the nearest reproductive tree. Thus, the results suggest that some seeds are dispersed by a seed dispersal vector. Investigation of genetic structure showed significant and negative correlation of genetic relatedness and spatial distances between the 30 potentially flowering trees, but this correlation was weak. We suggest that long-distance gene flow and seed migration are responsible for the poorly developed genetic structure of this species.
Ecosystem↗
Pulmonary sequelae in long-term survivors of bronchopulmonary dysplasia.
BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common problem in premature babies. Long-term sequelae are the main concerns. METHODS: A retrospective review of all BPD children born in Queen Mary Hospital, a teaching hospital of the University of Hong Kong, from January 1987 to December 1995 was conducted. Children with cerebral palsy, immunodeficiency, congenital heart disorders, renal or liver failure were excluded from analysis. Chest radiography (CXR), electrocardiogram (ECG) and pulse oximetry were routinely performed. RESULTS: Fifty-five children completed the study. The female to male ratio was 1:1.1. The mean gestational age was 28 weeks. Twenty-five children were born with a birthweight of less than 1001 g. Mean age at assessment was 5.4 years. Twenty-four children (44%) demonstrated signs or symptoms of current asthma. Only seven children managed to perform the spirometry satisfactorily. One child had low forced vital capacity and one had hyperresponsive airway. The only risk factor found to be associated with current asthma was the birth month, with those children born early in the year at higher risk of developing current asthma. Seventeen of 48 children (35%) had a bodyweight below the third percentile at the corrected age of 1 year. Eleven of these seventeen children (65%) demonstrated catch-up growth at assessment. Abnormal CXR was found in 25 of 40 children (63%). All had normal pulse oximetry and ECG. CONCLUSIONS: Bronchopulmonary dysplasia children had a significantly higher risk than the general population of developing current asthma (odds ratio 4.7; 95% confidence interval 3.4-6.5; P<0.0001). The importance of birth month suggests that early life experience is important in the pathogenesis of asthma, even in BPD children. The long-term growth of BPD children was much better than previously reported.
Asthma↗