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This study included 17 401 normal Han urban children aged 1-20 years from five cities in China in 2005. The skeletal maturity scores were assessed by the Tanner-Whitehouse 3 (TW3) method, and the smoothed centiles curves of scores (TW3-Chinese RUS and TW3-Chinese Carpal) were calculated using the LMS method. The skeletal maturity of the Chinese is approximately the same as Europeans in childhood, but the extent of TW3-RUS skeletal maturity advance in puberty and the ages of complete maturity of TW-Carpals are evidently more advanced in the Chinese.

Purpose: The two main goals of this phase-I study were to determine the maximum-tolerated dose (MTD) and to characterize the toxicity of the combination of pegylated liposomal doxorubicin (PLD; Lipo-Dox) and paclitaxel (PTX) administered on a 3-week schedule in patients with metastatic breast cancer (MBC) who had previously been treated with anthracycline-based therapy., Methods: This phase-I study was performed via a two-staged dose escalation schema. The initial doses were PLD 30 mg/m2 and PTX 150 mg/m2, administered intravenously once every 21 days. The dose of PLD was escalated in increments of 5 mg/m2 until the MTD was reached, at which time the PTX was then increased in increments of 10 mg/m2 until the MTD was reached., Results: Twenty-three patients received between 1 and 13 treatment cycles. In stage I of the study, 14 patients received a fixed dose of PTX 150 mg/m2 while PLD escalated from 30 mg/m2. At 40 mg/m2, PLD resulted in dose-limiting toxicities (DLT) including febrile neutropenia and palmar-plantar erythrodysesthesia that occurred in two of five patients. In stage II of the study, nine patients received fixed dose of PLD 35 mg/m2 and escalating doses of PTX starting at 160 mg/m2. At PTX 170 mg/m2 and dose-limiting neutropenic fever occurred in two of five patients. Out of 19 evaluable patients, 10 (52.6%) achieved objective response (one complete response and nine partial response), and 5 had stable disease., Conclusions: The maximal tolerated doses of PLD and PTX are 35 and 160 mg/m2, respectively, administered every 3 weeks. The combination of PLD (30-35 mg/m2) and PTX (150-160 mg/m2) constitutes an active regimen with mild toxicity that merits further study.

The Ku heterodimer facilitates the regulation of DNA repair, DNA replication, cell cycle, and telomere maintenance. The plant hormone abscisic acid (ABA) is a plant growth inhibitor. This study investigates how Arabidopsis thaliana Ku (AtKu) genes are regulated by ABA in 3-week-old seedlings. First, beta-Glucuronidase assay and real time quantitative PCR analysis results indicate that ABA represses the AtKu gene in a time- and concentration-dependent manner. However, adding of ABA biosynthesis inhibitors, fluride and tungate, did not eliminate AtKu suppression. Moreover, analysis of inhibitor treatments and ABA-responsive mutants suggested that AtKu repression by ABA was mediated through the pathway of extracellular Ca(2+), phospholipase D alpha, p38-type mitogen-activated protein kinase (MAPK), MAPK6 and ABA transcription factors, ABI3 and ABI5. Finally, no cross-talk in modulating AtKu gene expression existed between ABA and antagonist hormones (auxins and gibberellic acid).

The complete RNA genomic sequence of a new virus infecting Mikania micrantha, designated as Mikania micrantha wilt virus (MMWV), has been determined. The genomic sequence and the predicted gene products of MMWV were similar to those of the other viruses of the genus Fabavirus. The MMWV nucleotide sequence showed 75.6% identity to that of gentian mosaic virus, 56.6 and 57% identity to those of two Broad bean wilt virus 1 isolates, and between 55.7 and 58% identity to those of seven Broad bean wilt virus 2 isolates. Our results suggested that MMWV represents a distinct isolate of the candidate species Gentian mosaic virus.

Removal of PAEs by combined process of activated carbon-Fenton was investigated. Factors associated with PAEs removal ratio following amount of activated carbon, dosages of oxidant, catalyst, initial concentration of PAEs, pH value and reaction time were studied. Results showed that high purification performance could be obtained by the synergetic effect of Fenton reagent and activated carbon. Average removal ratio of PAEs was 99.1% for the solution containing 12 mg x L(-1) DMP, DEP, DBP, DOP respectively by the activated carbon-Fenton process for 15 h.

Most aspects of cellular events are regulated by a series of protein phosphorylation and dephosphorylation processes. Abi (Abl interactor protein) functions as a substrate adaptor protein for Abl and a core member of the WAVE complex, relaying signals from Rac to Arp2/3 complex and regulating actin dynamics. It is known that the recruitment of Abi into the lamella promotes polymerization of actin, although how it does this is unclear. In this study, we found PTP61F, a Drosophila homolog of mammalian PTP1B, can reverse the Abl phosphorylation of Abi and colocalizes with Abi in Drosophila S2 cells. Abi can be translocalized from the cytosol to the cell membrane by either increasing Abl or reducing endogenous PTP61F. This reciprocal regulation of Abi phosphorylation is also involved in modulating Abi protein level, which is thought to affect the stability of the WAVE complex. Using mass spectrometry, we identified several important tyrosine phosphorylation sites in Abi. We compared the translocalization and protein half-life of wild type (wt) and phosphomutant Abi and their abilities to restore the lamellipodia structure of the Abi-reduced cells. We found the phosphomutant to have reduced ability to translocalize and to have a protein half-life shorter than that of wt Abi. We also found that although the wt Abi could fully restore the lamellipodia structure, the phosphomutant could not. Together, these findings suggest that the reciprocal regulation of Abi phosphorylation by Abl and PTP61F may regulate the localization and stability of Abi and may regulate the formation of lamella.

Plant Ku genes were identified very recently in Arabidopsis thaliana, and their roles in repair of double-stranded break DNA and maintenance of telomere integrity were scrutinized. In this study, the cDNAs encoding Ku70 (VrKu70) and Ku80 (VrKu80) were isolated from mung bean (Vigna radiata L.) hypocotyls. Both genes were expressed widely among different tissues of mung bean with the highest levels in hypocotyls and leaves. The VrKu gene expression was stimulated by exogenous auxins in a concentration- and time-dependent manner. The stimulation could be abolished by auxin transport inhibitors, N-(1-naphthyl) phthalamic acid and 2,3,5-triiodobenzoic acid implicating that exogenous auxins triggered the effects following their uptake by the cells. Further analysis using specific inhibitors of auxin signaling showed that the stimulation of VrKu expression by 2,4-dichlorophenoxyacetic acid (2,4-D) was suppressed by intracellular Ca(2+) chelators, calmodulin antagonists, and calcium/calmodulin dependent protein kinase inhibitors, suggesting the involvement of calmodulin in the signaling pathway. On the other hand, exogenous indole-3-acetic acid (IAA) and alpha-naphthalene acetic acid (NAA) stimulated VrKu expression through the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Altogether, it is thus proposed that 2,4-D and IAA (or NAA) regulate the expression of VrKu through two distinct pathways.

Plant vacuolar H+-translocating inorganic pyrophosphatase (V-PPase EC 3.6.1.1) utilizes inorganic pyrophosphate (PPi) as an energy source to generate a H+ gradient potential for the secondary transport of ions and metabolites across the vacuole membrane. In this study, functional roles of arginine residues in mung bean V-PPase were determined by site-directed mutagenesis. Alignment of amino-acid sequence of K+-dependent V-PPases from several organisms showed that 11 of all 15 arginine residues were highly conserved. Arginine residues were individually substituted by alanine residues to produce R-->A-substituted V-PPases, which were then heterologously expressed in yeast. The characteristics of mutant variants were subsequently scrutinized. As a result, most R-->A-substituted V-PPases exhibited similar enzymatic activities to the wild-type with exception that R242A, R523A, and R609A mutants markedly lost their abilities of PPi hydrolysis and associated H+-translocation. Moreover, mutation on these three arginines altered the optimal pH and significantly reduced K+-stimulation for enzymatic activities, implying a conformational change or a modification in enzymatic reaction upon substitution. In particular, R242A performed striking resistance to specific arginine-modifiers, 2,3-butanedione and phenylglyoxal, revealing that Arg242 is most likely the primary target residue for these two reagents. The mutation at Arg242 also removed F- inhibition that is presumably derived from the interfering in the formation of substrate complex Mg2+-PPi. Our results suggest accordingly that active pocket of V-PPase probably contains the essential Arg242 which is embedded in a more hydrophobic environment.

A randomized, controlled trial was conducted to assess the effectiveness of Blue Angel for Asthma Kids, an Internet-based interactive asthma educational and monitoring program, used in the management of asthmatic children. One hundred sixty-four (n = 164) pediatric patients with persistent asthma were enrolled and randomized into two study groups for a 12-week controlled trial. The intervention group had 88 participants who were taught to monitor their peak expiratory flows (PEF) and asthma symptoms daily on the Internet. They also received an interactive response consisting of a self-management plan from the Blue Angel monitoring program. The control group had 76 participants who received a traditional asthma care plan consisting of a written asthma diary supplemented with instructions for self-management. Disease control was assessed by weekly averaged PEF values, symptom scores, and asthma control tests. Adherence measures were assessed by therapeutic and diagnostic monitoring. Outcome was assessed by examining quality of life and retention of asthma knowledge. The data were analyzed by comparing results before and after the trial. At the end of trial, the intervention group decreased nighttime (-0.08 +/- 0.33 vs. 0.00 +/- 0.20, p = 0.028) and daytime symptoms (-0.08 +/- 0.33 vs. 0.01 +/- 0.18, p =0.009); improved morning (241.9 +/- 81.4 vs. 223.1 +/- 55.5, p =0.017) and night PEF (255.6 +/- 86.7 vs. 232.5 +/- 55.3, p =0.010); increased adherence rates (p < 0.05); improved well-controlled rates (70.4% vs. 55.3%, p < 0.05); improved knowledge regarding self-management (93.2% vs. 70.3%, p < 0.05); and improved quality of life (6.5 +/- 0.5 vs. 4.3 +/- 1.2 on a 7-point scale, p < 0.05) when compared with conventional management. The Internet-based asthma telemonitoring program increases selfmanagement skills, improves asthma outcomes, and appears to be an effective and well-accepted technology for the care of children with asthma and their caregivers.

Splenectomy followed by bone marrow transplantation (BMT) has been applied successfully in the treatment of neuronopathic Gaucher disease (GD). GD in combination with schizencephaly has not previously been reported. We describe a girl who presented with hemiparesis and oculomotor apraxia since infancy, and thereafter developed progressive anemia, thrombocytopenia, hepatosplenomegaly, psychomotor retardation, and skeletal abnormalities. GD caused by homozygosity of the L444P mutation was diagnosed, in combination with schizencephaly. The child received enzyme replacement therapy for 3 years, followed by successful matched unrelated BMT without splenectomy. The strategy of BMT without splenectomy after a period of enzyme replacement may be feasible in neuronopathic GD.

Objective: To describe the incidence and clinical characteristics of acute severe high-altitude diseases in indigenous Tibetans., Methods: The medical records of indigenous Tibetan patients with high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE), who were treated in this hospital from June of 1956 to June of 2005, were retrospectively reviewed., Results: A total of 3 184 cases of high-altitude disease were recorded in this period. Twenty four patients (0.75%, 24/3 184), 21 with HAPE and 3 with HACE, were indigenous Tibetans. Risk factors or precipitating factors were found in all the 24 cases, including getting into even higher altitude, exertion, cold, and alcohol drinking. From clinical symptoms, physical signs and laboratory examinations, it was found that 9 cases were complicated with multi-organ dysfunction., Conclusion: Indigenous Tibetans who travel between the plateau and the plain or to even higher altitude can suffer from hypoxic injury, even acute severe high-altitude disease, which may be complicated by multi-organ dysfunction.

This paper proposes a new hybrid neural network (NN) model that employs a multistage online learning process to solve the distributed control problem with an infinite horizon. Various techniques such as reinforcement learning and evolutionary algorithm are used to design the multistage online learning process. For this paper, the infinite horizon distributed control problem is implemented in the form of real-time distributed traffic signal control for intersections in a large-scale traffic network. The hybrid neural network model is used to design each of the local traffic signal controllers at the respective intersections. As the state of the traffic network changes due to random fluctuation of traffic volumes, the NN-based local controllers will need to adapt to the changing dynamics in order to provide effective traffic signal control and to prevent the traffic network from becoming overcongested. Such a problem is especially challenging if the local controllers are used for an infinite horizon problem where online learning has to take place continuously once the controllers are implemented into the traffic network. A comprehensive simulation model of a section of the Central Business District (CBD) of Singapore has been developed using PARAMICS microscopic simulation program. As the complexity of the simulation increases, results show that the hybrid NN model provides significant improvement in traffic conditions when evaluated against an existing traffic signal control algorithm as well as a new, continuously updated simultaneous perturbation stochastic approximation-based neural network (SPSA-NN). Using the hybrid NN model, the total mean delay of each vehicle has been reduced by 78% and the total mean stoppage time of each vehicle has been reduced by 84% compared to the existing traffic signal control algorithm. This shows the efficacy of the hybrid NN model in solving large-scale traffic signal control problem in a distributed manner. Also, it indicates the possibility of using the hybrid NN model for other applications that are similar in nature as the infinite horizon distributed control problem.

Lifestyle factors are considered important for the pathogenesis of both nasopharyngeal and oropharyngeal carcinomas. In Taiwan, the incidence of nasopharyngeal carcinoma gradually decreased over the past 20 years, whereas that of oropharyngeal carcinoma increased rapidly. To compare the incidence trends of nasopharyngeal and oropharyngeal carcinomas in Taiwan, the age-period-cohort model was used to analyze epidemiologic data from 1981 to 2000 obtained from the Taiwan Cancer Registry. The calendar time period of 1986 to 1990 and the 1931 to 1940 birth cohort were used as reference groups for estimates of relative risk. For nasopharyngeal carcinoma, the incidence seemed to decrease in most age groups and was more prominent in women (30%) than in men (23%). For oropharyngeal carcinoma, the incidence increased in all age groups and was more prominent in men (391.4%) than in women (59.2%). Cohort effect was found for both nasopharyngeal and oropharyngeal carcinomas. The relative risk of nasopharyngeal carcinoma for the 1971 to 1980 birth cohort was 0.38 for women and 0.68 for men. The relative risk of oropharyngeal carcinoma for the 1971 to 1980 cohort was 45.67 for men and 2.69 for women. Change in lifestyle seemed to be an important factor for the difference in the incidence trend between nasopharyngeal and oropharyngeal carcinomas and between men and women.

UniCAP and multiple-antigen simultaneous test (MAST) are among the widely used specific allergen tests. The Phadiatop and Fx5 are the multi-allergen UniCAP screening tests for inhalant allergens and common food allergens, respectively. We compared the differences between Phadiatop-Fx5 and MAST as screening allergen tests to clarify the optimal tests for different groups of allergic patients. Serum samples of 224 consecutive allergic patients were tested with Phadiatop, Fx5 and MAST. Results of these allergen tests were compared and analyzed in subgroups categorized by age, serum IgE levels and the clinical departments where the patients were treated. We found that among the 224 patients, 155 patients (69.2%) tested positive with Phadiatop while 137 (61.1%) tested positive with MAST for inhalant allergens. Twenty patients were Phadiatop(+)/MAST(-), while only 2 were Phadiatop(-)/MAST(+). There were 57 patients (25.4%) who tested positive with Fx5, while 32 (14.3%) tested positive with MAST for food allergens. Thirty-eight patients were Fx5(+)/MAST(-), while 13 were Fx5(-)/MAST(+). The disagreement between these two tests was more apparent in food allergen tests than in inhalant allergen tests. Most cases of disagreement occurred in younger age groups and in the patient group with IgE > 500 IU/ml. These results suggested that UniCAP allergen screening tests might be more effective in certain patient groups as screening tests.

A novel series of histamine H3 receptor antagonists based on the 4-[(1H-imidazol-4-yl)methyl]piperidine template displaying low CYP2D6 and CYP3A4 inhibitory profiles has been identified. Structural features responsible for the reduction of P450 activity, a typical liability of 4-substituted imidazoles, have been established.

We report the discovery of novel histamine H(3) receptor antagonists based on 4-[(1H-imidazol-4-yl)methyl]piperidine. The most potent compounds in the series (e.g., 7) result from the attachment of a substituted aniline amide to the main pharmacophore piperidine via a two-methylene linker.

Background: A phase II study was conducted to evaluate the safety and efficacy of a gemcitabine plus vinorelbine combination (GV) for patients with cisplatin-resistant nasopharyngeal carcinoma (NPC)., Methods: Thirty-nine eligible patients received vinorelbine, 20 mg/m(2), followed by gemcitabine, 1,000 mg/m(2), on days 1 and 8 of each 21-day cycle., Results: Grade 3/4 neutropenia and thrombocytopenia occurred in 44% and 18% of patients, respectively, but there was only one episode of febrile neutropenia. Nonhematologic toxicities were mild and did not lead to any treatment withdrawal. The overall response rate was 36% (95% confidence interval [CI], 20% to 52%) in an intent-to-treat analysis, with one complete response (3%) and 13 partial responses (33%). The median response duration, progression-free survival, and overall survival were 5.1, 5.6, and 11.9 months, respectively., Conclusion: Given the moderately high activity and favorable toxicity profile, GV is a reasonable choice for patients with cisplatin-resistant NPC., ((c) 2005 Wiley Periodicals, Inc. Head Neck 28: XXX-XXX, 2005.)

Background: There is a lack of effective treatment for metastatic adenoid cystic carcinoma (ACC), a usually indolent tumor. We studied the efficacy of imatinib mesylate, a potent inhibitor of KIT tyrosine kinase, in patients with KIT-positive metastatic ACC., Method: Five patients with lung metastasis were treated in a pilot study with imatinib 400 mg by mouth twice a day. Mutations of c-kit and platelet-derived growth factor receptor (PDGFR)-alpha in tumors from these patients were analyzed., Results: Disease progression was noted in three of five patients during the short treatment periods, ranging from 2 to 3 weeks. Three patients died of disease within 6 months. No detectable mutations were found in c-kit and PDGFR-alpha., Conclusion: We observed an unexpected high progression rate of metastatic ACC within short periods during imatinib treatment. Use of imatinib to treat cancers without c-kit or PDGFR-alpha mutation should be approached with caution., ((c) 2005 Wiley Periodicals, Inc.)

Vacuolar H(+)-translocating inorganic pyrophosphatase (V-PPase; EC 3.6.1.1) is a homodimeric proton-translocase; it contains a single type of polypeptide of approximately 81kDa. A line of evidence demonstrated that the carboxyl terminus of V-PPase is relatively conserved in various plant V-PPases and presumably locates in the vicinity of the catalytic site. In this study, we attempt to identify the roles of the C-terminus of V-PPase by generating a series of C-terminal deletion mutants over-expressed in Saccharomyces cerevisiae, and determining their enzymatic and proton translocating reactions. Our results showed that the deletion mutation at last 5 amino acids in the C-terminus (DeltaC5) induced a dramatic decline in enzymatic activity, proton translocation, and coupling efficiency of V-PPase; but the mutant lacking last 10 amino acids (DeltaC10) retained about 60-70% of the enzymatic activity of wild-type. Truncation of the C-terminus by more than 10 amino acids completely abolished the enzymatic activity and proton translocation of V-PPase. Furthermore, the DeltaC10 mutant displayed a shift in T(1/2) (pretreatment temperature at which half enzymatic activity is observed) but not the optimal pH for PP(i) hydrolytic activity. The deletion of the C-terminus substantially modified apparent K(+) binding constant, but exert no significant changes in the Na(+)-, F(-)-, and Ca(2+)-inhibition of the enzymatic activity of V-PPase. Taken together, we speculate that the C-terminus of V-PPase may play a crucial role in sustaining enzymatic activity and is likely involved in the K(+)-regulation of the enzyme in an indirect manner.

Purpose: This study was undertaken to evaluate the utility of whole-body (18)F-FDG PET in monitoring therapeutic effect during induction chemotherapy (IC) and in predicting prognosis in patients with locoregionally advanced nasopharyngeal carcinoma (NPC)., Methods: Fifty patients who had histologically proven, locoregionally advanced NPC without distant metastasis and had received IC were recruited in this study. The study cohort consisted of 19 females and 31 males (age 17-72 years, mean 45.9+/-11.9). Whole-body (18)F-FDG PET was performed in each patient after completion of one (33 patients) or two (17 patients) courses of IC. Each patient was restaged on the basis of the (18)F-FDG PET results. Patients who were downstaged to stage I or II were classified as major responders; the rest were classified as non-major responders., Results: Only 1 of the 23 major responders subsequently developed local recurrence. At the time of data analysis, all major responders were alive; by contrast, of the 27 non-major responders, 15 had locoregional recurrence or distant metastasis and nine had died (seven of NPC and two of treatment-related complications). Kaplan-Meier survival analysis showed significantly longer recurrence-free survival and overall survival in major responders (56.4+/-9.2 and 58.1+/-2.2 months) as compared with non-major responders (33.7+/-23.2 and 44.7+/-20.0 months), with p<0.0001 and p=0.0024, respectively., Conclusion: The results of this study suggest that early restaging by a single whole-body (18)F-FDG PET scan after the first or second course of IC is useful for predicting therapeutic response and outcome in patients with locoregionally advanced NPC.

Transparent copper nanorod/nanowire arrays and anodic alumina oxide composite films have been prepared by alternating current electrodeposition, and their linear optical properties have been systematically characterized by absorption spectra. In the experimental spectra, there exist transverse and longitudinal resonance peaks, which are caused by the surface-plasmon resonance along the diameter and the length of the copper nanorods, respectively. The transverse resonance peak is affected by the diameter and aspect ratio of the nanorod. The longitudinal resonance peak appears at longer wavelength when a polarized light illuminates the film with an angle of incidence of about 70 degrees , where the angle is defined with respect to the surface normal. Moreover, the longitudinal resonance mode is sensitive to the polarization direction when compared with the transverse resonance mode.

Purpose: To evaluate efficacy and toxicity of cetuximab plus carboplatin in recurrent or metastatic nasopharyngeal carcinoma (NPC) resistant to platinum treatment., Patients and Methods: A multicenter, open-label, single-arm, phase II study in patients with epidermal growth factor receptor-expressing NPC who progressed on or within 12 months after termination of platinum-based chemotherapy for recurrent or metastatic disease. Cetuximab was administered at an initial dose of 400 mg/m2 followed by weekly doses of 250 mg/m2. Carboplatin area under the curve 5 was administered every 3 weeks up to a maximum of eight cycles., Results: Sixty patients were enrolled (46 males, 14 females; median age, 44.5 years; range, 23 to 64 years), and all patients were included in the intent-to-treat and safety analyses. Of the 59 patients assessable for efficacy, there were seven partial responses (11.7%), 29 patients (48.3%) with stable disease, and 23 patients (38.3%) with progressive disease, giving an overall response rate of 11.7% (95% CI, 4.8% to 22.6%). The median time to progression was 81 days in all patients and was longest in the group of patients with a confirmed response (173 days). The median overall survival time was 233 days in all patients. Six patients (10%) experienced serious treatment-related adverse events. Grade 3 or 4 toxicities occurred in 31 patients (51.7%); of these patients, only 19 (31.7%) were considered to have toxicity related to cetuximab., Conclusion: Cetuximab in combination with carboplatin demonstrates clinical activity and an acceptable safety profile in heavily pretreated patients with recurrent or metastatic NPC who had previously experienced treatment failure with platinum-based therapy.

Unlabelled: The aim of this retrospective study was to evaluate the sensitivity and prognostic significance of whole-body (18)F-FDG PET for nasopharyngeal carcinoma (NPC) patients for whom there was a suspicion of recurrence or metastasis by conventional radiologic or clinical findings during their follow-up examinations., Methods: Whole-body (18)F-FDG PET examinations were performed on 64 Taiwanese NPC patients (14 female, 50 male; mean age +/- SD, 45.8 +/- 13.0 y; age range, 16-75 y) 4-70 mo (mean +/- SD, 14.1 +/- 13.5 mo) after radiotherapy or induction chemotherapy followed by concurrent chemoradiotherapy from February 1997 to May 2001. The accuracy of (18)F-FDG PET detection for each patient was determined by the histopathologic results or other clinical evidence., Results: The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of (18)F-FDG PET images in the diagnosis of NPC recurrence or metastases and secondary primary cancers were 92%, 90%, 92%, 90%, and 91%, respectively. Furthermore, the presence of (18)F-FDG hypermetabolism was highly correlated with the survival time of NPC patients., Conclusion: Whole-body (18)F-FDG PET is a sensitive follow-up diagnostic tool for the evaluation of NPC recurrences and metastases. It is also an effective prognostic indicator for NPC patients. To determine the optimized utilization of (18)F-FDG PET in the follow-up for NPC patients, further cost-effectiveness analysis of (18)F-FDG PET in combination with conventional management is necessary.

Objective: To evaluate the conversion of macular function in diabetic macular edema (DME) after vitreous surgery., Methods: Seventeen eyes of 16 patients were assessed after pars plana vitrectomy for DME. Multifocal electroretinogram (mfERG) techniques were used to evaluate the effects of treatment on macular visual function, and retinal foveal thickness was determined by optical coherence tomography before and after vitrectomy. Patients were followed up continually for 7 months. The correlation between the change of tomographic features and visual functions were analyzed., Results: During the follow-up period, the retinal function in macular areas recovered and the foveal thickness decreased gradually. While compared with preoperative values, the response of positive wave (P1) have shown decreases in implicit time and increases in amplitude since the forth and fifth postoperative month respectively (P < 0.05). While compared between each postoperative period, the P1 responses have increased significantly since the forth postoperative month. The correlation between the increase of P1 amplitude in macular area and the decrease of retinal foveal thickness was significant (r = 0.954, P < 0.001)., Conclusions: Macular function get improvement gradually in DME after vitreous surgery; The restoration of macular function is coincident with the reduction of macular edema.

Objective: To study the changes in humoral immunological function and their clinical significance in cerebral hemorrhage., Methods: Among 115 cases of cerebral hemorrhage, there was low volume bleeding in 39 case, middle volume in 37 cases, and large volume in 39 cases. The ratios of CD19+-CD25+ and CD19+-CD25-B lymphocytes were determined by flow cytometry, and the content of IgA, IgG, IgM, and complement C3 were determined with scattered turbidimetry. The changes in humoral immunological function were compared in patients with different degrees of hemorrhage, and their variation in acute and recovery stages of disease were respectively assessed., Results: The ratios of CD19+-CD25+and CD19+-CD25-B lymphocyte, and the levels of IgA, IgG, IgM, and C3 were higher than those of controls (all P<0.05). The ratios of CD19+-CD25+ and CD19+-CD25- B lymphocyte, and the contents of IgA, IgG,IgM and C3 were increased with the increase in amount of hemorrhage(all P<0.05). The ratios of CD19+-CD25+ and CD19+-CD25-B lymphocytes in recovery stage were lower than those in acute stage (all P<0.05)., Conclusion: There are activations of humoral immunological functions in cerebral hemorrhage. The more abundant in hemorrhage and the severer in disease, the more predominant in the changes in humoral immunological functions.

Endoplasmic reticulum (ER)-enriched vesicles from etiolated hypocotyls of mung bean seedlings (Vigna radiata) were successfully isolated using Ficoll gradient and two-phase (polyethylene glycol-dextran) partition. The ER-enriched vesicles contained inorganic pyrophosphate (PPi) hydrolysis and its associated proton translocating activities. Antiserum prepared against vacuolar H+-pyrophosphatase (V-PPase, EC 3.6.1.1) did not inhibit this novel pyrophosphatase-dependent proton translocation, excluding the possible contamination of tonoplast vesicles in the ER-enriched membrane preparation. The optimal ratios of Mg2+/PPi (inorganic pyrophosphate) for enzymatic activity and PPi-dependent proton translocation of ER-enriched vesicles were higher than those of vacuolar membranes. The PPi-dependent proton translocation of ER-enriched vesicles absolutely required the presence of monovalent cations with preference for K+, but could be inhibited by a common PPase inhibitor, F-. Furthermore, ER H+-pyrophosphatase exhibited some similarities and differences to vacuolar H+-PPases in cofactor/substrate ratios, pH profile, and concentration dependence of F-, imidodiphosphate (a PPi analogue), and various chemical modifiers. These results suggest that ER-enriched vesicles contain a novel type of proton-translocating PPase distinct from that of tonoplast from higher plants.

Background: The human histamine H1 receptor is constitutively active and exhibits basal activation of nuclear factor-kappaB (NF-kappaB), an important modulator of allergic inflammation. Certain H1 antihistamines have recently been shown to inhibit basal NF-kappaB activity by stabilizing the H1 receptor in an inactive state, a phenomenon called 'inverse agonism'., Methods: We evaluated the effect of the new H1 antihistamine, desloratadine, on basal and histamine-stimulated NF-kappaB activity and compared it with the activities of other H1 antihistamines., Results: Transiently transfected COS-7 cells co-expressing NF-kappaB-luciferase and the H1 receptor exhibited constitutive NF-kappaB activity. H1 antihistamines reduced basal NF-kappaB activity (rank order of potency: desloratadine > pyrilamine > cetirizine > loratadine > fexofenadine). Histamine stimulated basal NF-kappaB activity 8-fold, which was blocked by H1 antihistamines (rank order of potency: desloratadine > cetirizine > pyrilamine > loratadine > fexofenadine). Neither histamine nor antihistamines had any effect on NF-kappaB activity in the absence of the H1 receptor., Conclusions: Desloratadine, acting through the histamine H1 receptor, inhibited basal NF-kappaB activity and can thus be classified as an inverse agonist. Inhibition of basal and histamine-stimulated NF-kappaB activity may help to explain previously reported inhibitory effects of desloratadine on allergic inflammatory mediators., (2004 S. Karger AG, Basel.)

In this paper, we present a gradient ascent learning method of the Hopfield neural network for bipartite subgraph problem. The method is intended to provide a near-optimum parallel algorithm for solving the bipartite subgraph problem. To do this we use the Hopfield neural network to get a near-maximum bipartite subgraph, and increase the energy by modifying weights in a gradient ascent direction of the energy to help the network escape from the state of the near-maximum bipartite subgraph to the state of the maximum bipartite subgraph or better one. A large number of instances are simulated to verify the proposed method with the simulation results showing that the solution quality is superior to that of best existing parallel algorithm. We also test the learning method on total coloring problem. The simulation results show that our method finds optimal solution in every test graph.

It is believed that human progesterone receptor (PR) contains a ligand binding subunit A (83 kDa) or subunit B (120 kDa) and 2 copies of heat shock proteins (hsp90) of molecular weight 90 kDa. To elucidate the mechanism of hormone binding, we employed radiation inactivation to determine its functional size. The functional masses determined in the presence of glycerol, molybdate and potassium chloride were 120+/-14, 124+/-13 and 130+/-20 kDa, respectively. From scatchard plot analysis, the radiation decreased the binding sites and increased the binding affinity of PR with ligand. The functional masses of PR dissolved in the three variant buffers were similar to the molecular weight of PR subunit B. The results implied that PR subunit B could bind with ligand despite hsp90 and hsp90 was not involved in the PR binding to progesterone.

Objective: To investigate the clinical significance of early nutritional support for patients with critical hypertensive intracerebral hemorrhage (HICH) in a critical condition after operation, and the rationale of different methods of nutritional support., Methods: One hundred and seven HICH patients after operation with Glasgow coma score (GCS) 6-8 were randomly divided into three groups: early enteral nutrition (EEN) group (38 cases); early parenteral nutrition (EPN) group (35 cases), conventional treatment controls (34 cases). They were given different nutritional supports 48 hours after operation. Changes in nutritional parameters and the clinical complications in three groups after treatment were observed, and the treatment effects after 3 months were compared., Results: At the end of first week after operation, nutrition parameters including albumin (ALb), hemoglobin (Hgb) in EEN and EPN groups were better than those in control group(P<0.05); at the end of second week, they were differences among three groups but without statistical significance (P>0.05). The complications were higher in EPN and control groups (P<0.05 or P<0.01). The outcome was assessed 3 months after the operation in term of activity of daily life (ADL), and the result was better in EEN group than that in EPN and control groups (P<0.005)., Conclusion: Postoperative HICH patients in critical condition could be benefited with EEN, and complications could be reduced with improved prognosis.

Objective: To study the localization of specific allergen of Dermatophagoides pteronyssinus., Methods: Through optical microscope, the specific allergens of D. pteronyssinus were observed in paraffin sections using D. pteronyssinus-specific IgE antibodies from the patient sera., Results and Conclusion: The digestive system was found occupying large parts of body cavity of D. pteronyssinus by HE staining, while the specific allergens of D. pteronyssinus were mostly occurred in the midgut tissue, gut contents, cuticle and reproductive system in the immunostained sections. The results also showed that many parts of D. pteronyssinus were recognized by the specific IgE antibodies obtained from allergic individuals to D. pteronyssinus, which provided a theoretic base for further study of isolation and purification of the specific allergen.

Human herpesvirus 8 has been implicated in the pathogenesis of a limited subset of lymphoproliferative disorders in adults, but its role in children is unclear. A prospective evaluation of children with atypical lymphocytosis residing in the Hualien area, where the incidence of adult Kaposi sarcoma is high, revealed 3 cases caused by human herpesvirus 8.

The outcome of nasopharyngeal carcinoma (NPC) treatment has greatly improved as advances in imaging techniques increase the accuracy of tumor mapping. Radiotherapy remains a common treatment for early disease, while concurrent chemoradiotherapy is being increasingly accepted as the standard treatment for advanced disease. Intensity modulation radiotherapy (IMRT) delivers a more conformal radiation dose to the target area and may spare normal organs such as parotid gland for patients with early stage disease. IMRT in conjunction with concurrent chemotherapy offers excellent tumor control with fewer complications. These benefits suggest it will become the mainstay of radiotherapy treatment for NPC. Prevention of distant metastasis remains a crucial objective. The potential of induction chemotherapy to reduce distant metastasis has gained increased attention. Adjuvant chemotherapy has been unsuccessful due to poor tolerability. For metastatic NPC, cisplatin-based chemotherapy is effective but limited by cumulative toxicities. Newer drugs such gemcitabine and vinorelbine have been shown to be active in salvage therapy when cisplatin-containing combinations have failed. Due to their advantageous toxicity profiles, new drugs may replace cisplatin-based combinations as first-line treatment for metastatic NPC in the near future. Signal transduction manipulation is promising but has not been shown to be an essential therapy. Immunotherapy, such as mini-transplant, may offer the chance for durable control without long-term treatment, but its efficacy remains to be demonstrated.

Background: The importance of detecting recurrence at an early stage in patients with malignant disease is well recognized. Circulating Epstein-Barr virus (EBV) DNA can be detected in patients with nasopharyngeal carcinoma (NPC). The objective of the current study was to assess the effectiveness of plasma EBV DNA monitoring in the early detection of NPC recurrence compared with conventional methods., Methods: Patients with NPC in two prospective clinical trials who had locoregional recurrences or distant metastases were recruited into the study. Clinical data on these patients were scrutinized for evidence of recurrence. EBV DNA copy numbers in the prospectively collected plasma samples were assayed retrospectively with real-time quantitative polymerase chain reaction analysis., Results: At the time of clinical recurrence, 65% of 26 patients with locoregional recurrences and all but 1 of 28 patients with distant failure had circulating EBV DNA. The difference between the time from completion of treatment to positivity for circulating EBV DNA and the time from completion of treatment to the first observed clinical abnormality was not statistically significant for patients with local recurrence (P=0.84). However, the time to the first detection of circulating EBV DNA was significantly shorter among patients with distant metastases (P<0.0001). The Kaplan-Meier estimated median time to the emergence of plasma EBV DNA was 190 days, with a 95% confidence interval (CI) of 95-300 days, and the median time to the first observed clinical abnormality was 295 days (95% CI, 276-361 days)., Conclusions: Monitoring plasma EBV DNA levels surpassed traditional methods for the early detection of distant failure in patients with NPC. The role of this technique should be evaluated in prospective studies that incorporate complementary advanced imaging technology., (Copyright 2004 American Cancer Society.)

Background: Sinonasal natural killer (NK)/T-cell or T-cell lymphoma behaves quite differently from other lymphomas. The objective of this study was to investigate clinical features, treatment outcomes, and failure patterns in patients with this type of sinonasal lymphoma., Methods: From September, 1977 to December, 2000, 77 patients with sinonasal NK/T-cell lymphoma or T-cell lymphoma who had received radiotherapy (R/T), chemotherapy (C/T), or both (R/T and C/T) were evaluated retrospectively., Results: Fifty-six patients (73%) had locoregional disease only, and 21 patients (27%) had systemic involvement. Forty-four patients (57%) achieved a complete remission (CR). The 5-year overall survival rate was 36% (median follow-up, 89 months). Achievement of CR was the only prognostic factor for survival in multivariate analysis. Among patients with locoregional disease, the CR rate was 63%, and the 5-year overall survival rate was 42%. Combined R/T and C/T or R/T alone resulted in better survival compared with C/T alone (5-year survival rates, 59%, 50%, and 15%, respectively; P = 0.01). Incidences of locoregional and systemic failure were 43% and 30%, respectively. Outcome was dismal for patients with systemic disease, with a CR rate of 43% and a 5-year survival rate of 25%. Only 2 of 21 patients had sustained remissions. The locoregional and systemic failure rates were 57% and 71%, respectively., Conclusions: Treatment outcomes were unsatisfactory for patients with locoregional and systemic sinonasal NK/T-cell or T-cell lymphoma. R/T could not control locoregional disease satisfactorily, and C/T was unable to eradicate systemic disease in many patients. High-dose therapy may be worth studying in these patients. New treatments should be investigated to increase remission rates, prevent failure, and improve survival., (Copyright 2003 American Cancer Society.)

Background and Objectives: Photodynamic therapy (PDT) has been proposed as an alternative approach in overcoming multidrug resistance (MDR) phenotype. To verify whether 5-aminolevulinic acid (ALA)-mediated PDT is effective in MDR cells, we studied the protoporphyrin IX (PpIX) content, intracellular localization, and phototoxicity in human breast cancer cells MCF-7 and derived MDR subline, MCF-7/ADR., Study Design/materials and Methods: The fluorescence kinetics of ALA-induced PpIX was evaluated by spectrofluorometer. The phototoxicity of MCF-7 and MCF-7/ADR cells was determined by tetrazolium (MTT) assays and clonogenic assay. Furthermore, Annexin V and propidium iodide (PI) binding assays were performed to analyze the characteristics of cell death after ALA-PDT., Results: MCF-7/ADR accumulated a lower level of PpIX as compared to parental MCF-7 cells. Significant phototoxicity was observed in MCF-7 and increased in a fluence-dependent manner with LD(50) around 8 J/cm(2). Compared to its parental counterpart, MCF-7/ADR cells were less sensitive to ALA photodynamic treatment and PDT-induced cytotoxicity did not increase in a dose responsive manner as the concentration of ALA increased or the fluence of light increased. ALA-PDT was less effective for MCF-7/ADR cells than MCF-7 cells even under the condition when these two cell lines contained the similar amounts of PpIX., Conclusions: These results indicate that, except for the MDR related characteristics, MCF-7/ADR cells might possess intrinsic mechanisms that render them less sensitive to ALA-PDT induced phototoxicity., (Copyright 2004 Wiley-Liss, Inc.)

Objective: To investigate the effect of vitrectomy combined with full endocular panretinal photocoagulation in patients with late stage of proliferative diabetic retinopathy (PDR)., Methods: Pars plana vitrectomy combined with full panretinal photocoagulation were undergone in 56 eyes (56 cases) with late stage of PDR, including 32 eyes with tractive retinal detachment. Preoperative and postoperative visual acuity, anterior segment by slit lamp and fundus examination by indirect ophthalmoscopy, as well as fluorescein angiography (FFA) were analyzed., Results: Retina were reattached in 52 eyes. Vitreous hemorrhage, retinal bleeding, exudation and neovascular changes were not observed in these eyes. Non-irrigated areas were not found in 28/32 eyes in which FFA examination has been performed. Final visual acuity was improved in 52 eyes., Conclusion: Full endocular panretinal photocoagulation with low energy is an effective and safe procedure with low rate of complications for the late stage of PDR.

We report a non-familial case of lumbosacral agenesis born to a type 1 diabetic mother who had hyperglycemia during pregnancy despite regular insulin therapy. The male baby was noted to have atrophy of pelvis, flattening of the buttocks, and deformity of the lower limbs at birth. Spinal X-ray film revealed total agenesis of lumbar, sacral, and caudal spines. Magnetic resonance image disclosed interruption of the spinal cord at the level of T12 and adhesion between the two malrotated kidneys. Peripheral blood cytogenetic study revealed a normal male karyotype. Recurrent episodes of respiratory distress and urinary tract infection had bothered the patient subsequently. It is suggested that lumbosacral agenesis, a severe congenital defect, might be one of the anomalies of diabetic embryopathy.

Fifty Taiwanese patients with relapsed and/or refractory multiple myeloma (MM) were treated with thalidomide on a dose-escalation schedule, commencing with 100 mg/d nightly and incremented either to the maximally tolerated dose or 800 mg/d. Twenty-two patients (44%) responded, with 10 (45.5%) classified as partial remission and 12 (54.5%) minimal response (MR). Complete response did not occur. Of the 28 non-responders, 14 were progressive disease and 14 stable. The median time from commencement of thalidomide treatment to initial achievement of MR was 29 days (range, 8~155), and the corresponding thalidomide dose was 200 mg/d (range, 100~500). The median tolerated dose of thalidomide for the entire sample was 400 mg/d (range, 100~800), with only two (4%) able to tolerate 800 mg/d. Comparing responsive and non-responsive patients, statistically significant differences were not demonstrated for any characteristics except for CRP level and percentage cytogenetic change, which was slightly higher in the latter group relative to the former. Of particular interest, 18 of the 22 responders experienced transient reduction of leukocyte count preceding the attainment of significant reduction in M-proteins in comparison to only four of the 28 non-responders (82% vs. 14%; p<0.001). The median time from commencement of thalidomide treatment to attainment of minimal leukocyte count was 28 days (range, 7~150), with a mean of 2.19x10(9)/l (range, 0.96~3.35x10(9)/l). Leukopenia was generally transient, with rapid recovery despite subsequent continuation of thalidomide. Levels of other non-hematologically adverse effects attributed solely to thalidomide were generally acceptable. For 25 patients, thalidomide treatment was supplemented with low-dose dexamethasone (4 mg, every other day). Of these, 11 had relapsed from and 14 were primarily refractory to thalidomide treatment. Nine of the 25 dexamethasone-supplemented patients were responders (36%). Of particular note were the unusual events noted with this thalidomide-dexamethasone combination, including vascular thrombosis, acute cholecystitis, idiopathic interstitial lung disease and sudden cardiac death. Our results suggest that thalidomide is also effective for Taiwanese patients with refractory and/or relapsed MM. Importantly, the transient reduction in leukocyte count after commencement of thalidomide treatment may serve as a clinical predictor for response. Adverse effects should be carefully monitored when combining thalidomide and dexamethasone, however.

To establish reference values of various immunophenotypic markers in B lymphocyte population in healthy Chinese adults and build background information for accurate interpretation of B cell immunophenotyping data in clinical practice, peripheral blood from 41 healthy adults were collected separately into test tubes containing EDTA-K(2) and stored in room temperature no more than 24 hours before analysis. Whole blood lysis technique and multiparameter flow cytometry were applied to immunophenotype B cells gated on CD19/SSC dot-plot. The results showed that CD22, CD20, CD62L, CD40, CD24, CD79b, CD79a, and FMC-7 were almost positive in the circulating B cell population, whereas CD11a, CD80, CD103, CD10, CD40L, CD54, CD95L, CD86, and CD95 were almost negative in the peripheral blood B lymphocytes. CD18, CD44, CD23, CD5, CD11c and CD43 were positive in different B cell subpopulations. 78% of B cells were IgD positive and ratio kappa/lambda was 1.26. The significance of all these markers in the differential diagnosis of lymphoproliferative diseases was discussed. The conclusion is that it is necessary to consider the qualitative and quantitative levels of expression of various markers in normal B cell population in order to accurately interpret the pathological immunophenotypic data in clinical practice. It is also important to note the immunotypic differences of B cells between Chinese and Western populations.

Objective: To explore the effects of the behavioral treatment on female sexual dysfunctions for the popularization of improved methods in China., Methods: Fifty-six voluntary female patients with psychiatric sexual disorders were treated after the basic training model of sensate focus by Masters and Johnson. Stress was laid on such aspects as breaking-away from the traditional thought, teaching healthy sex concepts, and imparting sexual knowledge and techniques. In addition to psychotherapy and behavioral treatment, the patients were required to correctly deal with their matrimonial and social problems. Their husbands were also required to participate actively in the treatment process., Results: Twenty-six cases recovered, 24 cases improved, and 6 cases failed(10.71%) the general rate of effectiveness being 89.29%., Conclusions: The behavioral treatment is remarkably effective in treating female sexual dysfunctions. However, there still remain such problems as long course of treatment and high requirement of doctor's expertise.

Background: It is known that 18-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) is effective in the early detection of residual/recurrent nasopharyngeal carcinomas (NPC). To compare FDG-PET with the conventional magnetic resonance imaging (MRI) for the detection of residual/recurrent NPC, the authors studied 67 follow-up cases of patients with NPC using both FDG-PET and MRI., Methods: From February 1997 to February 2001, 67 NPC patients (14 women, 53 men; age range, 16-67 years; mean age, 46.6 +/- 12.5 years) were recruited. Both FDG-PET and MRI of the head and neck area for each patient were performed at least 4 months (duration range, 4-70 months; mean, 14 +/- 13.5 months) after radiotherapy or radiotherapy with concurrent chemotherapy. The final diagnosis was confirmed by biopsy or clinical follow-up for at least 6 months., Results: The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of FDG-PET images were 100%, 93.4%, 95.5%, 87.5%, and 100%, respectively. In contrast, the sensitivity, specificity, accuracy, PPV, and NPV of the MRI scans were 61.9%, 43.5%, 49.3%, 33.3%, and 70.0%, respectively., Conclusions: The results of the current study suggest that FDG-PET is much more effective than MRI in detecting residual/recurrent NPC., (Copyright 2003 American Cancer Society.)

In this article, we present a solution to the maximum clique problem using a gradient-ascent learning algorithm of the Hopfield neural network. This method provides a near-optimum parallel algorithm for finding a maximum clique. To do this, we use the Hopfield neural network to generate a near-maximum clique and then modify weights in a gradient-ascent direction to allow the network to escape from the state of near-maximum clique to maximum clique or better. The proposed parallel algorithm is tested on two types of random graphs and some benchmark graphs from the Center for Discrete Mathematics and Theoretical Computer Science (DIMACS). The simulation results show that the proposed learning algorithm can find good solutions in reasonable computation time.