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Biomedical subjects

A Wu

Publications and source records attributed to A Wu.

At least 91 records · Page 5Linked to original sources

Evaluation of dose calculation algorithm of the peacock system for multileaf intensity modulation collimator.

PURPOSE: To evaluate the dose calculation algorithm used in the inverse treatment planning computer system for the intensity modulation multileaf collimator. METHODS AND MATERIALS: The inverse treatment-planning computer system calculates the intensities of multiple pencil beams to achieve an optimal distribution and modulates the beam intensity through the special multileaf collimator. The system's dose calculation algorithm made the two basic assumptions: (a) The tissue-maximum ratios (TMRs) of a single pencil beam have the same values as TMRs for raylines through each pencil beam that are determined from percentage depth dose isodose curves along the long axis of the 2 x 20 cm2 field with all leaves open; and (b) the relative output factors (ROF) of each pencil beam also have the same values as the rayline TMR at d(max) of the 2 x 20 cm2 field. To verify these two assumptions, a special multileaf collimator was installed to our linear accelerator which produces 4 MV x-rays. The TMRs and ROFs for the single leaves 1 through 10 were measured using an ion chamber and TLD dosimeter in either a water or a polystyrene phantom. The values of rayline TMRs were calculated from the measured crossplane isodose curves of the 2 x 20 cm2 field. Comparisons were made between these two sets of data. RESULTS: Based on our measurements, we found that the ROFs of a pencil beam obtained from the rayline TMRs at d(max) are as much as 7.6% greater than that of single pencil beams. The ROF of the 1 x 1 cm2 pencil beam is 4 and 6.5% less than that of a cluster of four neighboring pencil beams forming a 2 x 2 cm2, and a 2 x 20 cm2 field respectively. However, the rayline TMRs are generally larger than the TMRs of a single pencil beam. At a depth of 8 cm, the average depth in the middle of intracranial space, the rayline TMRs of the pencil beams of leaves 1 and 10 are 5.4 and 9% higher than a single pencil beam TMR at the same depth, respectively. Also interesting is to note that the TMRs of each of the single pencil beams were found to be equal. CONCLUSIONS: In our article, evaluations and comparisons of TMRs and ROFs were made for two extreme conditions. The measured values of TMRs and ROFs of a single beam have been shown to be significantly different from those used in the calculations. Because both the TMR and ROF are influenced by the scattering radiation in the same direction, the deviations for these two factors would be expected to be magnified. Thus, for the two extreme situations we have investigated, dose deviations would be on the order of 15%. In real patient treatment; of course, these deviations may be somewhat less, but still significant. Our results, however, show that further investigations are warranted.

Algorithms↗

Nonenzymatic free radical-catalyzed generation of thromboxane-like compounds (isothromboxanes) in vivo.

The isoprostanes (IsoPs) are novel bioactive prostaglandin-like compounds produced in vivo by free radical-catalyzed peroxidation of arachidonyl-containing lipids. Previously, we have identified IsoPs containing F-type and D- and E-type prostane rings that are formed by reduction and rearrangement of IsoP endoperoxide intermediates, respectively. We now explore whether thromboxane B2 (TxB2)-like compounds, termed B2-isothromboxanes (B2-IsoTxs), are formed by rearrangement of IsoP endoperoxides. Detection of these compounds was carried out using a stable isotope dilution mass spectrometric assay originally developed for quantification of cyclooxygenase-derived TxB2. Incubations of arachidonic acid with Fe/ADP/ascorbate for 30 min in vitro generated a series of peaks representing putative B2-IsoTx at levels of 62.4 +/- 21.0 ng/mg arachidonate. Using various chemical modification and derivatization approaches, it was determined that these compounds contained hemiacetal ring structures and two double bonds, as would be expected for B2-IsoTx. Analysis of the compounds by electron ionization mass spectrometry yielded multiple mass spectra similar to those of TxB2. B2-IsoTxs are also formed esterified to phospholipids; oxidation of arachidonyl-containing phosphatidylcholine in vitro followed by hydrolysis resulted in the release of large amounts of these compounds. To explore whether B2-IsoTxs are also formed in vivo, a well characterized animal model of lipid peroxidation consisting of orogastric administration of CCl4 to rats was used. Levels of B2-IsoTx esterified in lipids in the liver increased 41-fold from 2.5 +/- 0.5 to 102 +/- 30 ng/g of liver. In addition, circulating levels of free compounds increased from undetectable (<5 pg/ml) to 185 +/- 30 pg/ml after CCl4, a 37-fold increase. Thus, we have provided evidence that IsoTxs constitute another novel class of eicosanoids produced in vivo nonenzymatically by free radical-catalyzed lipid peroxidation. These studies thus expand our understanding of products of lipid peroxidation formed in vivo from the free radical-catalyzed peroxidation of arachidonic acid.

Animals↗

Diisopropylphosphorofluoridate-induced muscle hyperactivity associated with enhanced lipid peroxidation in vivo.

Acute exposure to acetylcholinesterase (AChE) inhibitors such as organophosphates and carbamates induces functional changes at the neuromuscular junctions, leading to fasciculations that ultimately cause muscle fiber necrosis. There is recent evidence that oxygen free radical formation may be a factor in the toxicity of these insecticides. One of the targets of free radical-induced injury is lipid peroxidation. The role of lipid peroxidation in diisopropylphosphorofluoridate (DFP)-induced muscle necrosis was investigated by quantifying two products resulting from the oxidation of lipids in muscle tissue-the thiobarbituric acid-malondialdehyde complex (TBA-MDA) and F2-isoprostanes, the latter being a novel and extremely accurate marker of lipid peroxidation in vivo. When compared with control animals, significant increases in MDA of 96% and in F2-isoprostanes of 56% were found in the diaphragms of rats treated with 2.0 mg/kg DFP after 60 min (P < 0.01). In rats pretreated with the neuromuscular blocking agent d-tubocurarine or the lazaroid U-78517F, an antioxidant, no DFP-induced increases in either MDA or F2-isoprostanes were observed. It is suggested that the AChE inhibitor-induced cholinergic hyperactivity initiates that accumulation of free radicals leading to lipid peroxidation, which may be the initiator of the AChE inhibitor-induced cell injury.

Animals↗

Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS. A double-blind, randomized, trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. ACTG 108 Study Group.

OBJECTIVE: To compare the tolerability and efficacy of three oral regimens for the treatment of patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia. DESIGN: A randomized, double-blind study. SETTING: 24 U.S. academic medical centers. PATIENTS: 181 patients with morphologically confirmed P. carinii pneumonia and alveolar-arterial oxygen differences (PAO2-PaO2) of 45 mm Hg or less. INTERVENTION: Patients were randomly assigned to receive trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for 21 days. Patients with a PAO2-PaO2 of 35 to 45 mm Hg at study entry also received prednisone. MEASUREMENTS: Serial clinical and laboratory evaluations for therapeutic response and toxicity. Therapeutic failure at day 21 was defined by any of the following: increase in PAO2-PaO2 of greater than 20 mm Hg; no remission of baseline signs and symptoms; and change in antipneumocystis therapy for reasons other than toxicity, intubation, or death. Dose-limiting toxicity was defined as discontinuation of therapy by the primary physician because of one or more adverse reactions. RESULTS: No statistically significant differences were seen among treatment groups in the proportions of patients who had dose-limiting toxicity (P=0.2), therapeutic failure (P>0.2), or a complete course of therapy (P>0.2). Survival during therapy or for 2 months thereafter did not differ among the three groups (P>.02). However, elevation of serum aminotransferase levels to more than five times the baseline levels was more frequent in the trimethoprim-sulfamethoxazole group (P=0.003), and one or more serious hematologic toxicities (neutropenia, anemia, thrombocytopenia, or methemoglobinemia) occurred more frequently in the clindamycin-primaquine group (P=0.01). CONCLUSIONS: The rates of dose-limiting toxicity, therapeutic failure, and survival did not differ among patients with AIDS who were receiving oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for mild to moderate P. carinii pneumonia. However, the limited sample size prevents the unequivocal demonstration of the equality of these three regimens. Differences in expected categories of toxicities associated with each regimen should guide the clinician in choosing first-line therapy, particularly for patients with baseline hepatic insufficiency or myelosuppression.

AIDS-Related Opportunistic Infections↗

Dose volume assessment of high dose rate 192Ir endobronchial implants.

PURPOSE: To study the dose distributions of high dose rate (HDR) endobronchial implants using the dose nonuniformity ratio (DNR) and three volumetric irradiation indices. METHODS AND MATERIALS: Multiple implants were configured by allowing a single HDR 192Ir source to step through a length of 6 cm along an endobronchial catheter. Dwell times were computed to deliver a dose of 5 Gy to points 1 cm away from the catheter axis. Five sets of source configurations, each with different dwell position spacings from 0.5 to 3.0 cm, were evaluated. Three-dimensional (3D) dose distributions were then generated for each source configuration. Differential and cumulative dose-volume curves were generated to quantify the degree of target volume coverage, dose nonuniformity within the target volume, and irradiation of tissues outside the target volume. Evaluation of the implants were made using the DNR and three volumetric irradiation indices. RESULTS: The observed isodose distributions were not able to satisfy all the dose constraints. The ability to optimally satisfy the dose constraints depended on the choice of dwell position spacing and the specification of the dose constraint points. The DNR and irradiation indices suggest that small dwell position spacing does not result in a more homogeneous dose distribution for the implant. This study supports the existence of a relationship between the dwell position spacing and the distance from the catheter axis to the reference dose or dose constraint points. Better dose homogeneity for an implant can be obtained if the spacing of the dwell positions are about twice the distance from the catheter axis to the reference dose or dose constraint points.

Brachytherapy↗

Characterization of appican, the chondroitin sulfate proteoglycan form of the Alzheimer amyloid precursor protein.

In this report we focus on the characterization of appican, the chondroitin sulfate proteoglycan form of amyloid precursor protein (APP), and the role that it and other proteoglycans may play in AD. Appican is expressed by certain transformed cell lines of neural origin, namely C6 cells and N2a neuroblastomas. It is detected in both human and rat brain and in primary cultures is expressed by astrocytes, but not neurons. The core protein of appican has been shown to be an alternatively spliced isoform of APP, lacking exon 15 of the APP gene, originally identified in leukocytes (L-APP). Splicing out of exon 15 results in the joining of exons 14 and 16, and formation of an Asp-Xaa-Ser-Gly consensus sequence for chondroitin sulfate chain attachment to serine 619 of L-APP, which lies 16 amino acids upstream of the A beta peptide sequence. Mutation of this serine residue to an alanine prevented chondroitin sulfate chain addition to the core protein. Levels of appican expression could be regulated by growth conditions independently of APP, suggesting that these molecules may serve distinct physiological roles within the cell. Morphological changes were also observed in both astrocytic and transformed cell cultures, that appeared to reflect changes in levels of appican expression. Preliminary data suggest that appican may be a strong cell adhesion molecule. Transfected C6 glioma cells overexpressing appican remained attached to tissue culture dishes markedly better than either C6 cells over-expressing exon-15 containing APP or WT C6 cells. Appican-enriched extracellular matrix (ECM) was also observed to serve as a much better substrate for attachment of N2a neuroblastomas, pheocromocytoma PC12 cells and primary astrocytes compared to APP enriched ECM.

Alzheimer Disease↗

Reduction of canine infarct size by bolus intravenous administration of liposomal prostaglandin E1: comparison with control, placebo liposomes, and continuous intravenous infusion of prostaglandin E1.

Prostaglandin E1 (PGE1) reduces experimental infarct size when administered by prolonged low-dose left atrial infusion during coronary occlusion. Liposomal delivery of PGE1 may enhance biologic activity and limit adverse hemodynamic effects. The purpose of this study was to test the hypothesis that intravenous bolus administration of liposomal PGE1 (TLC C-53, The Liposome Company, Princeton, N.J.) during coronary occlusion would result in myocardial salvage. We compared TLC C-53 (0.5 microgram/kg intravenous bolus at 10 and 100 min of occlusion of the left anterior descending coronary artery [LAD]), free PGE1 (0.1 microgram/kg/min infused 10 min after LAD occlusion until reperfusion), placebo liposomes, and control (n = 7 for each group) in an open-chest canine model of 2 hours of LAD occlusion and reperfusion. Infarct size as a percentage of risk area (mean +/- SD) in the control group (58.4% +/- 20.0%) was similar to that in animals given placebo liposomes (53.1% +/- 12.6%) but was significantly reduced in the groups given TLC C-53 (33.5% +/- 9.2%; p < 0.01) or free PGE1 (37.2% +/- 4.8%; p < 0.05) groups. Infarct salvage was significant (p < 0.05) for the TLC C-53-and PGE1-treated dogs compared with the control dogs, independent of collateral blood flow by analysis of covariance. Moreover, the ischemic-zone blood flow during reperfusion was significantly higher in the TLC C-53 group compared with the control group or the group receiving free PGE1. Neutrophil infiltration of ischemic myocardium was significantly inhibited by TLC C-53 as determined by myeloperoxidase assay. Unlike free PGE1, TLC C-53 did not cause significant tachycardia or hypotension during therapy. In conclusion, TLC C-53 administered intravenously during coronary occlusion significantly reduced infarct size, limited neutrophil infiltration, and improved myocardial blood flow during reperfusion without adverse hemodynamic consequences.

Alprostadil↗

Outcome studies for burn patients in Hong Kong: patients' satisfaction.

With the recent advances in burns treatment, many more survive the burn to experience pain, scarring, physical deformity, loss of function and psychological trauma. Pressure therapy prescribed by occupational therapists for more than 20 years in Hong Kong has proved its effectiveness in treating the visible scars. However, the inconvenience and impaired appearance that is brought about by these garments during the long phase of therapy bears some weight in worsening patients' social acceptance and happiness in life, also their families especially in children. The objects of the studies were to measure the subjective rating of the effectiveness of pressure therapy through patients' satisfaction towards treatment effectiveness and its effect on daily life. Seventy cases with burn injuries over 1 year previously were selected randomly among the centres for the survey. The scale used was ordinal from 1 to 6. Eleven items concerning treatment effectiveness, life at home, work and leisure aspects were questioned. Results were analysed into two streams-satisfaction towards pressure therapy and change of life satisfaction pre- and post-injury. Non-parametric tests were used for data analysis. Through the Wilcoxon Sign Rank Test and Cluster analysis, major determinants were identified. These factors also showed significant correlation with this demographic data. The conclusions helped to evaluate and improve the existing service in both the garment properties and our scope of therapy for these patients, especially in work rehabilitation and finally (sexual) counselling which should be addressed by a team with interdepartmental support.

Activities of Daily Living↗

Increased expression of keratinocyte growth factor messenger RNA associated with inflammatory bowel disease.

BACKGROUND & AIMS: Alterations in intestinal epithelial cell function are common in inflammatory bowel disease (IBD). Keratinocyte growth factor (KGF) is an epithelial cell-specific mitogen. The aim of this study was to examine IBD tissue for altered KGF expression. METHODS: Expression levels of the KGF and KGF receptor transcripts were analyzed by ribonuclease protection assay. The cellular localization of each transcript was determined using in situ hybridization. RESULTS: KGF messenger RNA levels were increased in inflamed IBD tissue in comparison with control tissues. In normal tissue, KGF messenger RNA was localized to the mesenchymal cells at the tip of the villi in the small intestine and directly underlying the mature enterocytes in the colon, whereas in IBD it was present throughout the lamina propria, although distinct from the germinal centers. The topographic distribution of the KGF in situ hybridization signal in IBD was similar to that observed for T lymphocytes. In contrast, KGF receptor transcripts were localized to the cryptal region of the mucosal epithelium in both normal and IBD tissue, with no apparent differences in the level of expression. CONCLUSIONS: The increased expression of KGF in IBD suggests that it may be involved in mediating the altered regulatory functions of intestinal epithelial cells in this disease.

Colon↗

[Effect of antisense c-erbB2 on biologic behaviour and chemotherapeutic drug sensitivity in human ovarian cancer cells].

OBJECTIVE: To explore the effects of antisense erbB2 on the biological behaviours and on chemotherapeutic drug sensitivity in human ovarian cancer cells. METHODS: A recombinant retroviral expression vector: pDOR-erbB-neo was constructed which contain the neomycin resistant gene and the erbB2 cDNA 3.8kb antisense fragment. pDOR-erbB-neo was introduced into human ovarian cancer cell line SKOV3 by lipofectin. The cells were selected with geneticin (G418). The cells transfected with pDOR-erbB-neo were named SKOV3-A2. RESULTS: Southern blot analysis confirmed the presence of the antisense erbB2 in transfected cells. Transfected cells showed no obvious changes in morphology. Compared with parental cells and with pDOR-neo transfected cells used as controls, the growth and DNA synthesis of antisense transfected cells, SKOV3-A2, were inhibited. Transfection with pDOR-erbB-neo rendered the cells significantly, more sensitive to chemotherapeutic drugs (5-fluorouracil, cisplatinum) than the parental cells. CONCLUSIONS: The effectiveness and the potentiality of antisense erbB2 in ovarian cancer gene therapy is demonstrated. c-erbB2 oncogene may be related to drug resistance in ovarian cancer cell.

Antineoplastic Agents↗

[Autocrine transforming growth factor-beta stimulates human ovarian cancer cell growth in vitro and in vivo].

OBJECTIVES: Our previous studies have shown that human ovarian cancer cell lines COC1 and COC2 secrete transforming growth factor-beta (TGF-beta) like substance in serum-free culture. In this study the effect of COC1 and COC2-produced TGF-beta like substance on COC1 and COC2 cell growth was investigated. METHODS: The COC1 and COC2 RPMI 1640 serum-free conditioned media SFCM (SFCM1 from COC1, SFCM2 from COC2) were prepared, and their activities were investigated on COC1 and COC2 cell growth (SFCM1 on COC1, SFCM2 on COC2) in vitro and in vivo, and compared with that of TGF-beta. RESULTS: SFCM1 and SFCM2 could separately promote COC1 and COC2 cell proliferation in culture with dose-dependent response, SFCM2 significantly promoted COC2 cell growth in BABL/C nude mice. Radioreceptor assay showed that both COC1 and COC2 expressed TGF-beta receptor (or binding site). The above mentioned SFCM growth-stimulating effects can be partially blocked by anti-TGF-beta antibody. CONCLUSION: The results suggest that there may be TGF-beta autocrine loop in the two ovarian cancer cell lines, which is associated with autonomous proliferation of COC1 and COC2 cells.

Adenocarcinoma↗

Study on the production of human interferon alpha-2b expressed in Escherichia coli.

The production process of human interferon alpha-2b was established in our institute. The human interferon alpha-2b was expressed in E. coli by using PL promotor. The production process consists of high cell density fermentation, refolding of the inclusion bodies, chromatography with Sephadex G-50 and DEAE, without using monocloning antibody affinity chromatography. After purification, about 500 mg of the human interferon alpha-2b was obtained from 1 kg wet cell harvested from 10 L fermentation broth. The biological activity shows 1-2 x 10(8) IU/mg protein. This production process is very simple and easy to scale-up. If this process adapted, it will save a lot of facility investment, space, and labor. Therefore, the cost will be reduced.

Chromatography, High Pressure Liquid↗

[Combined treatment for advanced vulvar cancer].

OBJECTIVE: To investigate the combined treatment of surgery and radiotherapy as well as prognosis significance for advanced vulvar cancer. METHODS: Fourty-three cases of advanced vulvar cancer treated by surgery and pre- and post-operative radiation were retrospectively analysed. Twenty-nine patients were treated by preoperative radiotherapy with surgery, fourteen by surgery with postoperative irradiation. 43 patients were underwent radical vulvectomy with inguinal lymphadenectomy (20 cases) and with biopsies of inguinal lymph nodes (16 cases). Partial resection of vagina, distant urethra or anus were done concurrently with radical vulvectomy in 41 patients with adjacent organs invaded. The effects with various doses of radiation for local tumor were compared and the recurrences in patients with tumor resected completely and with microresidual disease after surgery were analysed. RESULTS: The overall 5-yr survival rate was 45.0% for this group (by Kaplan-Meier). Patients received preoperative irradiation with dose maximum (Dm) > or = 40 Gy had a better tumor regression than with Dm < 40 Gy (75.0% vs 18.2%, P < 0.05). 4 out of 6 patients received postoperative irradiation Dm > 40 Gy were survived over 5-yr, in contrast, 2 out of 8 patients with Dm < or = 40 Gy were survived over 3 and 5 years respectively. The local recurrence rate was 25.0% in patients with no residual disease and 68.4% with microscopic tumor in the surgical margins or nearby (P < 0.05). CONCLUSION: The results demonstrate that the dosage of irradiation and the thoroughness of radical surgery are the most important factors influencing the prognosis.

Adult↗

Post-transcriptional regulation of the Na+/Ca2+ exchanger in aging rat heart.

Altered calcium homeostasis in the senescent heart appears to be the result, at least in part, of decreased Na+/Ca2+ exchange activity. To further investigate the basis of the decrease in Na+/Ca2+ exchange activity, Na+/Ca2+ exchanger gene expression in the heart was compared in 3 and 24 month old male Fischer 344 rats. Sarcolemmal vesicles prepared from left ventricle and septum showed reduced Na(+)-dependent Ca2+ uptake in 24 month old animals when compared to 3 month old animals (0.156 +/- 0.005 and 0.135 +/- 0.008 nmol Ca2+/mg/10 s; mean +/- S.E. for 3 month and 24 month old animals, respectively). Western analysis showed immunodetectable Na+/Ca2+ exchanger protein levels were decreased by 19% in 24 month old animals when compared to 3 month old animals. Poly(A+) RNA was purified from left and right ventricle and left and right atria and subjected to Northern analysis using digoxin labeled cDNA probes for the Na+/Ca2+ exchanger and actin. The Na+/Ca2+ exchanger probe labeled a 7 kb message in both ventricle and atria, while the actin probe labeled both beta-actin (2.2 kb) and alpha-actin (1.4 kb). The steady state level of expression of Na+/Ca2+ exchanger Poly(A+) RNA when normalized to beta-actin, was similar when ventricle and atria were compared. There were no observable differences in Na+/Ca2+ exchanger or alpha-actin Poly(A+) RNA steady state levels when comparing 3 and 24 month old animals. The results suggest that reduced Na+/Ca2+ exchange activity in the left ventricle of 24 month old animals was most likely the result of post-transcriptional modification of the protein that was detectable by Western analysis.

Aging↗

Quality assurance for gamma knife stereotactic radiosurgery.

PURPOSE: This quality assurance program is designed for stereotactic radiosurgical units, gamma knife, to check and maintain the unit to preclude accidents and comply with current regulations. MATERIALS AND METHODS: Over 58 stereotactic radiosurgical units using 201 focused 60Co beams have been installed in the last 7 years and are in use at hospitals throughout the world, with at least 11 additional units being prepared to come on-line in the next year. This system has been in use at the University of Pittsburgh Medical Center (UPMC) for 7 years. A comprehensive quality assurance program has been developed. It includes the physics and dosimetry parameters and safety checks required by regulatory agencies. The program, based on over 7 years of experience in measurements, and used during the treatment of over 1500 patients, is separated into three aspects, namely physics, dosimetry, and safety. The UPMC program hopefully will indicate out-of-tolerance problems. Some quality assurance items are checked on a daily basis prior to patient treatment, while other aspects are checked on a weekly, monthly, and/or annual basis. A complete list of items with their respective time tables and tolerances is provided. RESULTS: Although experience shows very small margins of error, larger values were chosen to account for variations in equipment and techniques. CONCLUSIONS: Items included in this quality assurance program should indicate and/or preclude problems encountered in the use of this unit.

Cobalt Radioisotopes↗