Clinical target volume of high-grade glioma.
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Publications and source records attributed to S W Chen.
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BACKGROUND: To study the intra-thoracic failure pattern, clinical target volume (CTV) and survival status following 3D conformal radiotherapy (3DCRT) boost for non-small cell lung cancer (NSCLC). METHODS: From May 1994 through June 1998, 33 patients (26 male, seven female) with NSCLC were treated with a complete course of radiotherapy (RT) in our institute. Group A included 10 patients receiving radical operation and adjuvant postoperative RT. The other 23 patients (groups B and C) received definitive radiotherapy as local treatment. Among them there were seven cases as group B (stage I-II) and 16 cases as group C (stage III). Fifteen (15/33) patients received chemotherapy. The radiotherapy strategy constituted conventional AP/PA radiotherapy (RT) 19.8-45 Gy (median 39.6 Gy) plus 3DCRT boost 6-34.2 Gy (median 20 Gy). The median total tumor dose was 59.6 Gy (ranging from 39.8 to 64.8 Gy). Patients were followed up regularly (6/33) or until their death (27/33). Nineteen patients received follow-up chest computed tomography (CT). The relationship between intra-thoracic failure found by chest CT and the initial RT and boost RT fields was analyzed. Local failure was defined as one of the following: clinical disease progression, CXR progression or relapse noted by CT. The overall survival (OS) and local failure free survival (LFF) were obtained using the Kaplan-Meier method. RESULTS: Sixteen intra-thoracic failures were noted in 15 follow-up chest CT examinations, which included nine in-field relapses, three partial in-field relapses and four out-field relapses. The 2-year OS and LFF for groups A, B and C were 78.8/59.2, 14.2/16.7 and 6.2/7.1% respectively. RTOG grade III/IV complications included one pneumothorax (RTOG grade III). CONCLUSION: Our retrospective study showed that selective omission of contralateral mediastinal lymph node station irradiation may be appropriate in RT for NSCLC. Chest wall and pleural relapses may not be a negligible cause of intra-thoracic failure after RT for NSCLC.
PURPOSE: This study aimed to correlate patient, treatment, and dosimetric factors with the risk of late rectal sequelae in patients with uterine cervical cancer treated with external beam radiation therapy (EBRT) and high dose rate intracavitary brachytherapy (HDRICB). METHODS AND MATERIALS: From September 1992 to December 1995, a total of 128 patients with uterine cervical cancer, who were treated and survived more than 12 months, were evaluated. After EBRT with 40-44 Gy/20-22 Fr/4-5 weeks to the whole pelvis, the dose was boosted up to 54-58 Gy with central shielding for patients with bilateral parametria of Stage IIb or greater. HDRICB consisted of three to four insertions at doses of 5-7.2 Gy (to Point A) at intervals of 1 week. Patient and treatment factors were analyzed using logistic regression analysis and the cumulative rectal biologic equivalent dose (CRBED) was calculated. RESULTS: After 30-75 months of follow-up (median, 43 months), 38 patients (29.7%) had late rectal sequelae. Patients who had Stage IIb-IVa disease, cumulative rectal dose (external RT + total ICRU rectal dose) greeater than 65 Gy, or age greater than 70 years had a high risk of developing late rectal sequelae. When 110 Gy was used as the cut-off value, 19.6% (10 of 51) of patients whose CRBED was less than 110 Gy had rectal complications, while 36.4% (28/77) of patients whose CRBED was greater than 110 Gy developed rectal complications. CONCLUSION: Risk factors of late rectal complications were advanced stage, age greater than 70 years, and cumulative rectal dose of greater than 65 Gy.
In utero and lactational exposure to a single maternal dose of 1 microg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg causes some overt toxicity and impairs prostate growth in male offspring. As similar effects on the ventral prostate can be caused by decreased testosterone production during perinatal development, we determined whether intratesticular testosterone content, testicular responsiveness to gonadotropin stimulation, or plasma testosterone concentrations were reduced in fetal and newborn rats. Because these endpoints were not affected, the ability of TCDD exposure to inhibit synthesis of the proximal androgen in prostate development, 5alpha-dihydrotestosterone (DHT), from the circulating precursor testosterone and 5alpha-androstane-3alpha,17ss-diol (3alpha-Diol), was studied on postnatal days (PNDs) 14, 21, and 32. The ability of the ventral prostate to form DHT from 3alpha-Diol was slightly impaired on PND 14, but this transient effect was not statistically significant, and recovery was evident by PND 21. Subsequent experiments used organ culture to study the effects of in vivo TCDD exposure on androgen metabolism, androgen responsiveness, androgen receptor expression, and luminal epithelial cell differentiation after in vitro exposure to graded androgen concentrations. In utero and lactational TCDD exposure had no effect on DHT formation in organ culture, but transiently reduced the androgen -induced expression of prostatic-binding protein subunit C3, decreased ventral prostate epithelial cell androgen receptor expression, and inhibited the formation of androgen responsive luminal epithelial cells. These results suggest that TCDD exposure impairs prostate growth and androgen responsiveness by inhibiting prostatic epithelial cell differentiation.
In this paper, we describe a new approach for the discrimination among ventricular fibrillation (VF), ventricular tachycardia (VT) and superventricular tachycardia (SVT) developed using a total least squares (TLS)-based Prony modeling algorithm. Two features, dubbed energy fractional factor (EFF) and predominant frequency (PF), are both derived from the TLS-based Prony model. In general, EFF is adopted for discriminating SVT from ventricular tachyarrhythmias (i.e., VF and VT) first, and PF is then used for further separation of VF and VT. Overall classification is achieved by performing a two-stage process to the indicators defined by EFF and PF values, respectively. Tests conducted using 91 episodes drawn from the MIT-BIH database produced optimal predictive accuracy of (SVT, VF, VT) = (95.24%, 96.00%, 97.78%). A data decimation process is also introduced in the novel method to enhance the computational efficiency, resulting in a significant reduction in the time required for generating the feature values.
BACKGROUND AND PURPOSE: The cerebral endothelial cells (ECs) are a primary target of hypoxic or ischemic brain insults. EC damage may contribute to postischemic secondary injury. Massive production of NO after inducible NO synthase (iNOS) expression has been implicated in cell death. This study aimed to characterize bovine cerebral EC death in relation to iNOS expression after oxygen-glucose deprivation (OGD) in vitro. METHODS: OGD in bovine cerebral ECs in culture was induced by deleting glucose in the medium and by incubating the cells in a temperature-controlled anaerobic chamber. The extent of cell death was assessed by trypan blue exclusion, MTT assay, and LDH release. ELISA, gel electrophoresis, and staining by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling were used to examine DNA fragmentation. The expression of iNOS mRNA and protein was detected by reverse transcription-polymerase chain reaction and Western blotting, respectively. Nitrotyrosine expression was confirmed with Western blot analysis and immunostaining. RESULTS: Bovine cerebral EC death was dependent on the duration of OGD and showed selected biochemical, morphological, and pharmacological features suggestive of apoptosis. OGD also induced the expression of iNOS mRNA and protein in bovine cerebral ECs. Increased expression of nitrotyrosine, the product formed by peroxynitrite reaction with proteins, was also detected after OGD. The involvement of iNOS in EC death was suggested by partial reduction of cell death by NO synthase inhibitors, including L-N(G)-(1-iminoethyl)ornithine and nitro-L-arginine, and an NO scavenger, the Fe(2+)-N-methyl-D-glucamine dithiocarbamate complex. CONCLUSIONS: OGD-induced bovine cerebral EC death involves an apoptotic process. Induction of iNOS with subsequent peroxynitrite formation may contribute to bovine cerebral EC death caused by OGD.
An automated gas chromatographic system was constructed to easily adapt either the cryogenic trap or chemical sorbent trap for preconcentrating ambient levels of volatile organic compounds. Remarkable similarity in chromatograms from C3 to C10 was found between these two enrichment methods, except that the sorbent trap did not quantitatively trap the C2-hydrocarbons. In contrast to cryogenic trapping, the chromatographic conditions for more volatile compounds were substantially improved using the sorbent trap. Water interference on the porous-layer open tubular column was also better managed using the sorbent trap for the continuous analysis of humid room air. The similarity in peak profiles between the GC-flame ionization detection (FID) and a commercial GC-MS system, regardless of concentration levels, facilitated compound identification on the FID chromatograms based on a field mission involving analysis of 106 air samples.
This study is to improve the digestion pattern of miniprepped plasmid analyzed on gel. Frequently, some ambiguous DNA bands, which are suspected to be denatured DNA molecules, appear during electrophoresis of enzyme digested miniprepped plasmids. By employing Southern hybridization of two identical gels, one had been treated with denaturation-neutralization step and another without such treatment, we confirmed that many of these ambiguous DNA bands were single-stranded (SS) DNA molecules. The presence of SS DNA was due to the use of excess amount of NaOH during plasmid DNA purification with the conventional alkaline lysis method. We, therefore, modified the procedure and recommend that a half amount of NaOH (0.1N instead of 0.2N) should be used when isolating small quantity of plasmid DNA with the method.
The murine Hoxa1 gene is a member of the vertebrate Hox complex and plays a role in defining the body plan during development. At day 8.0-9.0 post coitus, Hoxa1 transcripts are detected extensively throughout the embryo in the neural tube, adjacent mesenchyme, paraxial mesoderm, somites and gut epithelium; expression extends from the most caudal region of the embryo to the rhombomere 3/4 border. This spatiotemporal expression of Hoxa1 mRNA is critical for normal embryonic development. We have previously identified a 10 bp element, called CE2, which is located approximately 3 kilobases 3' of the Hoxa1 coding region in the RAIDR5 enhancer, and which binds to an approximately 170 kd protein in retinoic acid treated P19 embryonal carcinoma cells. CE2 elements were also identified 3' of the murine Hoxb1 gene, the chicken Hoxb1 gene and the human Hoxa1 gene. To examine the role of this CE2 element in regulating Hoxa1 expression in vivo, transgenic mice were generated which express a Hoxa1 beta-galactosidase reporter gene that contains a mutation in the CE2 element. Relative to transgenic mice bearing a wild type CE2 element, the mutant CE2 construct recapitulated rhombomeric, neural, and gut epithelium expression but failed to show beta-galactosidase expression in somites and adjacent mesenchymal tissue. Gel shift analysis showed that binding activity similar to that detected in extracts prepared from retinoic acid treated P19 cells was present in nuclear extracts prepared from day 9.0 embryos. However, an additional binding complex not detected in P19 cells was also observed. These results indicate that in transgenic animals, the evolutionary conserved CE2 element is a somite and adjacent mesenchymal enhancer of Hoxa1 expression.
OBJECTIVE: To evaluate radiotherapy dose and length of treatment in the control of early stage nasopharyngeal carcinoma (NPC) treated with a combination of external radiotherapy and brachytherapy, MATERIALS & METHODS: We reviewed the records of 133 patients with early stage nasopharyngeal carcinoma (stage I or II, AJC/UICC staging system) who received definitive radiotherapy in Chang Gung Memorial Hospital from 1979 to 1991. The median follow-up time was 7.1 years with a minimum of 2 years. All patients were treated with megavoltage external radiotherapy to the nasopharynx area (63-72 Gy) followed by high dose rate intracavitary brachytherapy (5-16.5 Gy in one to three fractions, spaced 1-2 weeks apart). The median total dose and time of irradiation was 75 Gy (69.8-81.4 Gy) and 11.6 weeks (7.8-20 weeks) respectively. Survival analysis was used to examine the effect of several variables on prognosis. RESULTS: The 5-year rates were 86.4% for local control, 84.7% for disease free survival, 88.5% for actuarial survival and 84.2% for overall survival. The treatment group (combination of time and dose of irradiation) was the most important prognostic factor according to Cox's proportional hazard model. Patients receiving radiation at a total dose of < or = 75 Gy completed in < 12 weeks showed the best prognosis. CONCLUSION: Treatment time and total treatment dose are both important factors in treating early stage NPC. Decreasing the total radiation time to < 12 weeks and not exceeding a radiation dose of 75 Gy gave the best results.
A case is presented in which calcification in an axillary lymph node seen on a screening mammogram was the presenting feature of metastatic papillary carcinoma, presumed to be of thyroid origin. The differential diagnosis of axillary lymph node calcification seen on mammography is reviewed.
The present report of four cases highlights the potential for focal organizing pneumonia (FOP) to masquerade as a small peripheral lung adenocarcinoma on CT scans. Both entities may present the CT appearance of a peripheral spiculated lung nodule, often with an air bronchogram. A history suggestive of an infectious aetiology and the presence of other foci of inflammatory change on CT scan may be helpful clues to the diagnosis of FOP. Because FOP is comparatively rare, surgical excision will usually be required to exclude malignancy. In some cases, however, particularly after a negative percutaneous biopsy, conservative management with a follow-up CT scan at 3-4 weeks may be an alternative to immediate surgical intervention.
The murine Hoxb-1 gene contains a homeobox sequence and is expressed in a spatiotemporal specific pattern in neuroectoderm, mesoderm and gut endoderm during development. We previously identified a conserved retinoic acid (RA)-inducible enhancer, named the RAIDR5, which contains a DR5 RARE; this RAIDR5 enhancer is located 3' of the Hoxb-1-coding region in both the mouse and chick. In the F9 murine teratocarcinoma cell line, this DR5 RARE is required for the RA response of the Hoxb-1 gene, suggesting a functional role of the DR5 RARE in Hoxb-1 gene expression during embryogenesis. From the analysis of Hoxb-1/lacZ reporter genes in transgenic mice, we have shown that a wild-type (WT) transgene with 15 kb of Hoxb-1 genomic DNA, including this Hoxb-1 3' RAIDR5, is expressed in the same tissues and at the same times as the endogenous Hoxb-1 gene. However, a transgene construct with point mutations in the DR5 RARE (DR5mu) was not expressed in the developing foregut, which gives rise to organs such as the esophagus, lung, stomach, liver and pancreas. Like the wild-type transgene, this DR5 RARE mutated transgene was expressed in rhombomere 4 in 9.5 day postcoitum (d.p.c.) embryos. Similarly, transgene staining in the foregut of animals carrying a deletion of the entire Hox-b1 RAIDR5 enhancer (3'-del) was greatly reduced relative to that seen with the WT transgene. We also demonstrated that expression of the WT transgene in the gut increases in response to exogenous RA, resulting in anterior expansion of the expression in the gut. These observations that the Hoxb-1 gene is expressed in the developing gut and that this expression is regulated through a DR5 RARE strongly suggest a role for Hoxb-1 in the anteroposterior axis patterning of the gut and a critical role for endogenous retinoids in early gut development.
Most ocular tumors metastasize from systemic origins in breast carcinoma in females, and bronchial carcinoma in males. Here, we report a case of choroidal carcinoma metastasis from the breast with visual problems being the only initial manifestations. In this case, both eyes were involved at almost the same time, with initial manifestation of blurred vision which progressed to complete visual loss. At first, the patient was diagnosed with malignant melanoma, and enucleation of the right eye was performed in another hospital. However, the tumor had already metastasized rapidly to numerous organs, including the lungs, brain and bone, although it had not affected the liver. Clinical presentations were, therefore, not compatible with those of malignant melanoma, which has usually been reported to metastasize to the liver. Persistent hypercalcemia and raised carcinoembryonic antigen (CEA) concentrations prompted investigations into the possibility of systemic malignancy. A very small breast nodule was finally located by thorough physical examination, and a lumpectomy was performed. A detailed review of the histopathology showed the tumors from the breast and the right eye to have the same origin. Simultaneous bilateral choroidal metastases from other malignancies is not uncommon; however, it is quite rare for breast carcinoma to present with visual problems as a first manifestation. Detailed history taking and physical examination are therefore essential when searching for a primary tumor, so that appropriate therapy can be given earlier.
Limitations in protein homology modeling often arise from the inability to adequately model loops. In this paper we focus on the selection of loop conformations. We present a complete computational treatment that allows the screening of loop conformations to identify those that best fit a molecular model. The stability of a loop in a protein is evaluated via computations of conformational free energies in solution, i.e., the free energy difference between the reference structure and the modeled one. A thermodynamic cycle is used for calculation of the conformational free energy, in which the total free energy of the reference state (i.e., gas phase) is the CHARMm potential energy. The electrostatic contribution of the solvation free energy is obtained from solving the finite-difference Poisson-Boltzmann equation. The nonpolar contribution is based on a surface area-based expression. We applied this computational scheme to a simple but well-characterized system, the antibody hypervariable loop (complementarity-determining region, CDR). Instead of creating loop conformations, we generated a database of loops extracted from high-resolution crystal structures of proteins, which display geometrical similarities with antibody CDRs. We inserted loops from our database into a framework of an antibody; then we calculated the conformational free energies of each loop. Results show that we successfully identified loops with a "reference-like" CDR geometry, with the lowest conformational free energy in gas phase only. Surprisingly, the solvation energy term plays a confusing role, sometimes discriminating "reference-like" CDR geometry and many times allowing "non-reference-like" conformations to have the lowest conformational free energies (for short loops). Most "reference-like" loop conformations are separated from others by a gap in the gas phase conformational free energy scale. Naturally, loops from antibody molecules are found to be the best models for long CDRs (> or = 6 residues), mainly because of a better packing of backbone atoms into the framework of the antibody model.
Several fentanyl analogs (Bagley et al., 1989, J. Med. Chem. 32, 663) were compared to fentanyl and morphine for their effects on respiratory depression as determined by arterial blood gas (pH, pCO2 and pO2) measurements. Fentanyl (0.1 mg/kg), morphine (10 mg/kg), #16 (1-phenethyl-4-[N-(pyridin-2-yl)-N-(methoxymethylcarbonyl)amino] piperidine, 1 mg/kg), #17 (1-phenethyl-4-[N-(pyridin-2-yl) -N-(2-furoyl)amino]piperidine, 0.5 mg/kg) and #29 (1-phenethyl-4-[N- (pyrimidin-2-yl)-N-(methoxy-methylcarbonyl) amino]piperidine, 10 mg/kg) produced significant respiratory depression in rats. Pretreatment with the mu1-opioid receptor selective antagonist, naloxonazine (10 mg/kg), blocked the respiratory effect of fentanyl and its analogs, but not that of morphine. The results suggest that the mu1-opioid receptor plays an important role in the respiratory effects of fentanyl and its analogs. Hence, the mechanism of fentanyl-induced respiratory depression appears to be distinct from that produced by morphine. The most likely explanation for this difference is the possible contribution of muscle rigidity and catalepsy to the observed changes in blood gas parameters caused by the fentanyl analogs, while the respiratory depression of morphine, measured by these same parameters, appears to be independent of its effect on muscle rigidity.
The vegetal plate of the sea urchin embryo is specified during early cleavage divisions of the embryo as shown by the classical experiments of Horstadius (reviewed in "Experimental Embryology of Echinoderms," 1973, Clarendon, Oxford). Not until gastrulation, though, do the cells within this territory differentiate into their characteristic cell types. Vegetal plate descendents comprise the coelomic epithelium, circumesophageal muscle, basal cells, pigment cells, and endodermal epithelium. We report here that cells of the endodermal lineage acquire the ability to differentiate autonomously several hours prior to gastrulation, between the late blastula and early mesenchyme blastula stages. Cells dissociated from whole embryos after the late blastula stage have the ability to differentiate in vitro, independent of cell contacts and of the embryonic environment. In contrast, preendoderm cells removed from the embryo prior to the late blastula stage show no ability to differentiate when cultured in vitro even though cells of other lineages, e.g., ectoderm and skeletogenic mesenchyme, show morphological and molecular differentiation in these same cultures. We have used the expression of the endoderm-specific gene products Endo 1 and LvN1.2, detected by RNase protection assays and by in situ immunolabeling, to quantify endoderm differentiation independent of embryonic or cellular morphology. These studies define a transitional period in the ontogeny of the endoderm, from cells reliant on interactions to promote fate specification and organization of territories to later events involved in morphogenesis that result from cell-type-specific gene expression.
Exposure to elevated temperature provokes a sequence of events (heat shock response) in all living organisms. Through this response, heat shock proteins (HSPs) are induced and protect the cells against subsequent injury. We investigated the effect of heat treatment on bicuculline-induced convulsions, and analyzed a possible role of HSPs. Screw electrodes were implanted in the brain of mature male Wistar rats for electroencephalogram (EEG) recording. Experimental rats were subjected to whole-body hyperthermia at 41-42 degrees C for 15 min. Fifteen hours later, bicuculline was injected intraperitoneally to induce convulsions in both experimental and control groups. The heated rats showed a significant attenuation of the convulsive response, in terms of both spike discharges in EEG and clinical seizures. Further-more, induction of HSP72 was detected in the brain of heat-treated rats by immunoblotting, appearing at 4 h and reaching a maximal level 16-24 h after the heat shock. We conclude that the previous heat treatment stabilized neuronal excitability, most probably through the induction of HSP72.