Retraction.
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Biomedical and Behavioral Research↗
Biomedical subjects
C L Hsieh
Publications and source records attributed to C L Hsieh.
Evaluation of stroke patients with the extended activities of daily living scale in Taiwan.
PURPOSE: This study examined the construct validity of the Nottingham Extended Activities of Daily Living scale (EADL) in stroke patients in Taiwan. METHODS: The EADL and the Barthel Index were administered via telephone interview. Minor revisions were made for the EADL to reflect cultural differences and the recommendations of two previous studies on the use of EADL. One hundred and fifty three stroke patients from the community participated in the study. RESULTS: Two items, 'make hot snack' and 'write letters', were deleted from the EADL because they appeared to be of little discriminative value. The results suggest that a changed hierarchical order was present among the domestic and leisure subscales. All of the subscales, then, fulfilled the Guttman scaling criteria (coefficient of reproducibility > 0.9, coefficient of scalability > 0.6). The scores of the revised EADL were significantly related to age and the Barthel Index scores (Spearman correlation coefficients = -0.41 and 0.69, respectively, p < 0.001). There was no significant difference between the overall scores of men and women (median = 10, 10, respectively, Mann-Whitney U test, p = 0.67). CONCLUSION: These data support the validity of the EADL with minor modifications in the evaluation of the functional performance in stroke patients in Taiwan and confirm it to be a useful outcome measure in stroke research.
Activities of Daily Living↗
Stable RNA/DNA hybrids in the mammalian genome: inducible intermediates in immunoglobulin class switch recombination.
Although it is well established that mammalian class switch recombination is responsible for altering the class of immunoglobulins, the mechanistic details of the process have remained unclear. Here, we show that stable RNA/DNA hybrids form at class switch sequences in the mouse genome upon cytokine-specific stimulation of class switch in primary splenic B cells. The RNA hybridized to the switch DNA is transcribed in the physiological orientation. Mice that constitutively express an Escherichia coli ribonuclease H transgene show a marked reduction in RNA/DNA hybrid formation, an impaired ability to generate serum immunoglobulin G antibodies, and significant inhibition of class switch recombination in their splenic B cells. These data provide evidence that stable RNA/DNA hybrids exist in the mammalian nuclear genome, can serve as intermediates for physiologic processes, and are mechanistically important for efficient class switching in vivo.
Animals↗
Tumor-induced immunosuppression: a barrier to immunotherapy of large tumors by cytokine-secreting tumor vaccine.
An active immunotherapy strategy with cytokine-assisted tumor vaccine, although often effective for small tumor burdens, is much less so for large tumor burdens. This study examines how large tumors might suppress the T cell functions and escape from the immune responses elicited by a granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccine. According to our results, the T cells isolated from the tumor-bearing mice treated late with the vaccine failed to confer protective activity on naive mice against a wild-type tumor challenge, unlike those isolated from the early-treated group. Nevertheless, the antitumor activity of the inactive T cells could be restored on in vitro stimulation. Expression of transforming growth factor beta (TGF-beta) and interleukin 10 (IL-10), the potent immunosuppressive factors, was detected in the parental tumor cell line RLmale 1 (a murine T leukemia cell line), as well as in the tumor region, the levels of which correlated with tumor progression. An in vitro assay of T cell functions revealed that the TGF-beta in the conditioned medium of RLmale 1 cells mainly affected the activation, whereas the IL-1male affected the activation to a lesser extent, but significantly affected the cytolytic activity, of tumor-specific T cells. The immunosuppressive activity of IL-10 was also signified by the findings that administration of the conditioned medium of RLmale 1 cultured in a serum-free medium, in which the TGF-beta activity was then lost while the IL-10 activity still remained, or of recombinant IL-10 to the early-treated group of mice abrogated the known efficacy of tumor vaccine on the small tumors. These data suggested that the efficacy of cytokine-secreting tumor vaccine was blocked by the immunosuppressive factors secreted from the large tumors. The results have important implications for the clinical design of immunotherapeutic strategies for advanced cancer patients.
Animals↗
Antioxidant actions of du-zhong (Eucommia ulmoides Oliv.) toward oxidative damage in biomolecules.
This study aimed to investigate the antioxidant effect of water extracts of Du-zhong (WEDZ) on oxidative damage in biomolecules such as deoxyribose, DNA, and 2'-deoxyguanosine (2'-dG) as induced by Fenton reaction. The WEDZ used included leaves, raw cortex, and roasted cortex. All of the WEDZ inhibited the oxidation of deoxyribose induced by Fe(3+)-EDTA/H2O2/ascorbic acid in a concentration dependent manner. At a concentration of 1.14 mg/mL, the inhibitory effect of the extracts of leaves, roasted cortex, and raw cortex was 85.2%, 68.0% and 49.3%, respectively. The extract of leaves inhibited the strand-breaking of DNA induced by the Fenton reaction at concentrations of 5 and 10 micrograms/microL. This inhibitory effect was similar to mannitol whereas the extracts of raw cortex and roasted cortex had no inhibitory effect at all. WEDZ also inhibited the oxidation of 2'-dG to 8-OH-2'-dG induced by Fe(3+)-EDTA/H2O2/ascorbic acid. Gallic acid had a prooxidant effect, but trolox and mannitol had an antioxidant effect. The leaf extract had a marked inhibitory effect on Fenton reaction induced oxidative damage in biomolecules. The extract of roasted cortex exhibited modest inhibition while the extract of raw cortex had the least inhibitory effect on oxidative damage in biomolecules. This is in contrast to gallic acid in the same reaction system, whose higher reducing power and weaker chelating ability may contribute to its prooxidant effect. In the present study, leaf extract of Du-zhong had inhibitory effect on oxidative damage in biomolecules. Therefore, drinking of Du-zhong tea (leaf extract) over a long period of time may have anticancer potential.
Antibiotics, Antineoplastic↗
Anticonvulsive and free radical scavenging activities of vanillyl alcohol in ferric chloride-induced epileptic seizures in Sprague-Dawley rats.
Vanillyl alcohol (VA) is a component of Gastrodia elata Bl. (GE), which is a traditional Chinese herb widely used to treat convulsive disorders or dizziness. This study examined the role of VA in the anticonvulsive properties of GE in a Sprague-Dawley rat model of epilepsy. The anticonvulsive and free radical scavenging activities of VA were examined after intracortical injection of ferric chloride (100 mM, 8 microl) to induce epileptic seizures. These seizures were verified by behavioral observations and electroencephalographic (EEG) and electromyographic (EMG) recordings. Ferric chloride injection resulted in increased lipid peroxide levels in the ipsilateral and contralateral cerebral cortex, and increased luminol-chemiluminescence (CL) and lucigenin-CL counts in the peripheral blood. Intraperitoneal injection (i.p.) of VA (200 mg/kg or 100 mg/kg) or phenytoin 10 mg/kg prior to ferric chloride administration significantly inhibited wet dog shakes (WDS) and lipid peroxide levels in the bilateral cerebral cortex. VA 200 mg/kg also significantly reduced luminol-CL and lucigenin-CL counts in the peripheral blood, but no significant effect was observed following administration of VA 100 mg/kg or phenytoin. These data indicate that VA has both anticonvulsive and suppressive effects on seizures and lipid peroxidation induced by ferric chloride in rats. Data from the present study also demonstrate that VA has free radical scavenging activities, which may be responsible for its anticonvulsive propertics. This finding is consistent with the results from previous studies that generation of superoxide radical evoked by injection of iron salt into rat brain plays a critical role in ferric chloride-induced seizures. In addition, the results of the present study suggest that the anticonvulsive effect of GE may be attributable, at least in part, to its VA component.
Acridines↗
Peripheral nerve regeneration using silicone rubber chambers filled with collagen, laminin and fibronectin.
A 10 mm gap of rat sciatic nerve was created between the proximal and distal nerve stumps, which were sutured into silicone rubber tubes filled with an extracellular gel containing collagen, laminin and fibronectin. Empty silicone rubber tubes were used as controls. Six weeks after implantation, all extracellular elements were completely degraded and absorbed, and 90% of the animals from the extracellular gel group exhibited regeneration across the nerve gaps, whereas only 60% in the control group. Both qualitative and quantitative histology of the regenerated nerves revealed a more mature ultrastructural organization with 28% larger cross-sectional area and 28% higher number of myelinated axons in the extracellular gel group than the controls. These results showed that the gel mixture of collagen, laminin and fibronectin could offer a suitable growth medium for the regeneration of axons.
Action Potentials↗
Protective effect of extracts of Mesona procumbens Hemsl. on DNA damage in human lymphocytes exposed to hydrogen peroxide and UV irradiation.
In the present study, the protective effect of water extracts from Hsian-tsao (WEHT) on DNA damage in human lymphocytes induced by UV-C and/or H(2)O(2) was evaluated using single-cell electrophoresis (comet assay). No toxicity was found in WEHT towards human lymphocytes. WEHT did not cause DNA damage at lower concentrations of 0.05 and 0.1 mg/ml, while it did cause slight DNA damage at a concentration of 0.5-2.5 mg/ml when compared with the control group. When WEHT was mixed with H(2)O(2) for reaction, it exhibited a slight inhibitory effect on DNA damage induced by H(2)O(2). Moreover, when WEHT and lymphocytes were irradiated by UV-C and then incubated for 35 min, the DNA damage decreased with an increase of the concentration of WEHT. Thus, WEHT could reduce UV-C-induced DNA damage, and WEHT had a more protective effect on UV-C than on H(2)O(2)-induced DNA damage. The protective effect of WEHT on DNA damage might be due to the fact that it contains polyphenol compounds and/or other active components.
DNA Damage↗
Dynamics of DNA methylation pattern.
Methylation patterns are the result of de novo methylation, demethylation, and the maintenance of existing methylation. Although the existence and identity of an active demethylase remain in doubt, recent evidence suggests that protein binding can specify sites of demethylation through a replication-dependent pathway. By using a stable episomal system in human cells, plus the Drosophila system, and mouse embryonic stem cells, we are beginning to understand the function and targets of de novo methyltransferases in murine and human cells.
Animals↗
Reactive oxygen species scavenging activity of Du-zhong (Eucommia ulmoides oliv.) and its active compounds.
The biologically active compounds and free radical-/ or reactive oxygen species (ROS)-/ scavenging effect of water extract from Du-zhong (WEDZ) were investigated. The WEDZ used included leaves, raw cortex, and roasted cortex. The hot water extract of Du-zhong leaves showed marked activity as a ROS scavenger, and the scavenging effect was concentration dependent. The extract of roasted cortex exhibited a modest scavenging effect on ROS, while the extract of raw cortex had the weakest scavenging effect. The scavenging activity of WEDZ on ROS was correlated to its protocatechuic acid (PCA) content. The content of PCA in Du-zhong determined by HPLC followed the order of leaves (17.17 mg/g) > roasted cortex (2.99 mg/g) > raw cortex (1.16 mg/g). The inhibitory activity of leaf extract of Du-zhong was stronger than that of PCA on the peroxidation of linoleic acid at the same concentration of 0.1 mg/mL. The results presented herein indicated that extract of Du-zhong could possibly act as a prophylactic agent to prevent free radical-related diseases.
Free Radical Scavengers↗
Validity and responsiveness of the rivermead mobility index in stroke patients.
The Rivermead Mobility Index is used to measure mobility in patients with head injury or stroke. The purpose of the study was to examine construct validity, predictive validity, and the responsiveness of the Rivermead Mobility Index in stroke patients. Thirty-eight stroke inpatients participated in the study. The Rivermead Mobility Index, the Barthel Index, and the Berg Balance Scale were administered at admission to the rehabilitation ward and at discharge. The results showed that the Rivermead Mobility Index fulfilled the Guttman scaling criteria (coefficients of reproducibility > 0.9, coefficients of scalability > 0.7). The Rivermead Mobility Index scores were highly correlated with the Barthel Index scores (Spearman rs > 0.6) and the Berg Balance Scale scores (Spearman rs > = 0.8, all ps < 0.001). The Rivermead Mobility Index score at admission was closely correlated with the Barthel Index score at discharge (Spearman r = 0.77, p < 0.001). About 76% (29) of the subjects improved by more than 3 Rivermead Mobility Index points (median = 5) during their stay. The relationship between the change in score of the Rivermead Mobility Index and the Barthel Index was fair (Spearman r = 0.6, p < 0.001). These results indicate that the Rivermead Mobility Index is valid and sensitive to change over time. It is therefore a useful scale for the assessment of mobility in stroke patients.
Disability Evaluation↗
The mammalian FEN-1 locus: structure and conserved sequence features.
Flap endonuclease 1 (FEN-1) is an enzyme that is very important for DNA replication in all eukaryotes because it cleaves the 5' DNA flaps that arise between Okazaki fragments. In addition, FEN-1 is important for base excision repair and for nonhomologous DNA end joining in all eukaryotes from yeast to human. Here we report the structure and sequence of the murine genomic FEN-1 locus, and we compare it to the human FEN-1 locus. The transcriptional initiation zone of FEN-1 is within a CpG island, and the coding region of FEN-1 is a single exon in both the murine and human genomes. There are striking regions of nucleotide sequence homology within the 5' or 3'UTR or immediately upstream of the 5'UTR. These regions range from 30 to 230 bp. The functions of these conserved sequence blocks could be in transcriptional regulation, or they may represent a gene that overlaps in its initiation zone with FEN-1, but is oriented in the opposite transcriptional direction.
3' Untranslated Regions↗
Modulation of DNA binding protein affinity directly affects target site demethylation.
It has recently been shown that in Xenopus, DNA demethylation at promoter regions may involve protein-DNA interactions, based on the specificity of the demethylated sites. Utilizing a stable episomal system in human cells, we recently mapped the sites and dissected the steps of demethylation at oriP sites bound by EBNA1 protein. Although it is clear that protein binding is required for demethylation of the oriP sites, it is uncertain whether this is a unique feature of the replication origin or whether it is a general phenomenon for all DNA sequences to which sequence-specific proteins are bound. In the present study, we utilize the well-defined Escherichia coli lac repressor/operator system in human cells to determine whether protein binding to methylated DNA, in a region that is neither a replication origin nor a promoter, can also lead to demethylation of the binding sites. We found that demethylation specified by protein binding is not unique to the replication origin or to the promoter. We also found that transcriptional activity does not influence demethylation of the lac operator. Isopropyl-beta-D-thiogalactopyranoside (IPTG), an inhibitor of the lac repressor, can prevent demethylation of the lac operator DNA sites and can modulate demethylation of the lac operator by affecting the binding affinity of the lac repressor. Using this system, a titration of protein binding can be done. This titration permits one to infer that protein binding site occupancy is the determinant of demethylation at DNA sites and permits a determination of how this process progresses over time.
Bacterial Proteins↗
Analgesic effect of electric stimulation of peripheral nerves with different electric frequencies using the formalin test.
Although electroacupuncture (EA) has been widely used to treat pain, the optimal frequency of EA therapy remains unclear. The study sought to determine the effect of different EA frequencies in a Sprague-Dawley (SD) rat model of pain. Electric stimulation (ES) at frequencies of 2 Hz, 15 Hz or 100 Hz was applied to the ipsilateral or contralateral sciatic nerve of the injected hindpaw of SD rats. Formalin (50 microl, 5%) was subcutaneously injected into the plantar surface of the left hindpaw to induce a nociceptive response. Behavior, including licking and biting, was observed to have two distinct periods, an early phase during the first 5 mins and a late phase from 21-35 mins after injection. The total biting or licking count served as an Indicator of nociceptive response. Our results indicate that ES of the ipsilateral sciatic nerve at a frequency of 2 Hz or 15 Hz reduced the nociceptive responses in both the early and the late phases of the formalin test, whereas ES at 2 Hz had greater antinociceptive effect than ES at 15 Hz in the early phase. No similar analgesic effect in the early phase was observed for ES at 100 Hz. Both pretreatment with ES at 2 Hz and naloxone (3 mg/kg, s.c.) produced a greater antinociceptive response in the late phase than when ES at 2 Hz was delivered immediately after formalin administration. In addition, ES of the neck muscle or contralateral sciatic nerve at a frequency of 2 Hz also decreased licking and biting activity in both phases. The results of this study indicate that different analgesic mechanisms are involved in the response to ES at frequencies of 2 Hz, 15 Hz and 100 Hz, and that ES at 2 Hz has a greater analgesic effect on formalin-induced nociceptive response, especially when it is delivered prior to the onset of pain. The analgesic effect of ES may be mediated via a central origin in the supraspinal level. These findings suggest that 2 Hz may be a good frequency selection for clinical EA applications in analgesia, and that pretreatment with EA at 2 Hz may be an effective method to treat post-operative pain.
Analgesia↗
Induction of antitumor immunity with combination of HER2/neu DNA vaccine and interleukin 2 gene-modified tumor vaccine.
The therapeutic effects of both cytokine-secreting tumor vaccine and DNA vaccine were studied using mouse MBT-2 bladder cancer cells as a model. Cytokine-secreting MBT-2 cells were obtained by infecting cells with retroviral particles containing interleukin (IL) 2-, IL-4-, or granulocyte-macrophage colony-stimulating factor (GM-CSF)-expression vector. The MBT-2-IL-2 cells were not tumorigenic in syngenic C3H mice at all. Tumor formation decreased significantly for the MBT-2-GM-CSF cells. MBT-2-IL-2, -IL-4, and -GM-CSF cells were killed by irradiation and tested as tumor vaccines. The irradiated MBT2-IL-2 cells could complete protect mice from the growth of the preexisting tumor cells, and the immune memory lasted for 8 months. On the other hand, irradiated MBT-2-IL-4 and MBT-2-GM-CSF cells were less effective. When the loading tumor mass increased, all tumor vaccines lost protective effects. DNA vaccine encoding the tumor antigen neu was additionally tested to improve the therapeutic efficacy. Coinjection of 60 microg pSV-neu DNA was effective in enhancing the antitumor effects of MBT2-IL-2; however, DNA vaccine alone cannot prevent the progression of the preexisting tumor. Immunohistochemical analysis of tumor infiltrate revealed massive increase of CD4+ lymphoid cells in the group of mice treated with both DNA vaccine and IL-2-secreted tumor vaccine. Western blotting demonstrated the presence of anti-neu antibody in the serum from immunized mice. In contrast, combination of DNA vaccine and MBT-2-GM-CSF has no additive effect. The results indicate the combination of DNA vaccine and IL-2-secreting tumor vaccine can additionally improve therapeutic efficacy, and the efficacy is correlated with the increase of CD4+ T lymphocytes and anti-neu antibody.
Animals↗
Characterization of saccharide-CRM197 conjugate vaccines.
A seven-valent pneumococcal conjugate and a Group C Meningococcal conjugate are at the late stage of development. Clinical studies have demonstrated the efficacy and safety of these vaccines and licensure of these vaccines will be approved in the near future. Several new techniques have been proposed for characterizing polysaccharide-protein conjugates and their production intermediates. We are evaluating some of these new techniques, particularly NMR and MALLS, to determine whether or not they provide useful information for conjugate production. In the production of polysaccharide protein conjugates, the degree of saccharide activation, location of activation site, and the molecular weight of activated saccharides may typically be determined. In our evaluation, techniques such as NMR and MALLS may have a limited applicability for testing polysaccharides and activated saccharides.
Animals↗
Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene.
The recessive autosomal disorder known as ICF syndrome (for immunodeficiency, centromere instability and facial anomalies; Mendelian Inheritance in Man number 242860) is characterized by variable reductions in serum immunoglobulin levels which cause most ICF patients to succumb to infectious diseases before adulthood. Mild facial anomalies include hypertelorism, low-set ears, epicanthal folds and macroglossia. The cytogenetic abnormalities in lymphocytes are exuberant: juxtacentromeric heterochromatin is greatly elongated and thread-like in metaphase chromosomes, which is associated with the formation of complex multiradiate chromosomes. The same juxtacentromeric regions are subject to persistent interphase self-associations and are extruded into nuclear blebs or micronuclei. Abnormalities are largely confined to tracts of classical satellites 2 and 3 at juxtacentromeric regions of chromosomes 1, 9 and 16. Classical satellite DNA is normally heavily methylated at cytosine residues, but in ICF syndrome it is almost completely unmethylated in all tissues. ICF syndrome is the only genetic disorder known to involve constitutive abnormalities of genomic methylation patterns. Here we show that five unrelated ICF patients have mutations in both alleles of the gene that encodes DNA methyltransferase 3B (refs 5, 6). Cytosine methylation is essential for the organization and stabilization of a specific type of heterochromatin, and this methylation appears to be carried out by an enzyme specialized for the purpose.
Alleles↗
Anticonvulsive and free radical scavenging actions of two herbs, Uncaria rhynchophylla (MIQ) Jack and Gastrodia elata Bl., in kainic acid-treated rats.
Uncaria rhynchophylla (Miq.) Jack (UR) and Gastrodia elata BI. (GE) are traditional Chinese herbs that are usually used in combination to treat convulsive disorders, such as epilepsy, in China. The aim of this study was to compare the anticonvulsive and free radical scavenging activities of UR alone and UR in combination with GE in rats. For the in vitro studies, brain tissues from 6 male Sprague-Dawley (SD) rats were treated with 120 microg/ml kainic acid (KA), with or without varied concentrations of UR or UR plus GE. For the in vivo studies, male SD rats (6 per group) received intraperitoneal (i.p.) injection of KA 12 mg/kg to induce epileptic seizures and generation of free radicals, with or without oral administration of UR 1 g/kg alone or UR 1 g/kg plus GE 1 g/kg. Epileptic seizures were verified by behavioral observations, and electroencephalography (EEG) and electromyography (EMG) recordings. These results showed that UR alone decreased KA-induced lipid peroxide levels in vitro, whereas UR plus GE did not produce a greater effect than UR alone. UR significantly reduced counts of wet dog shakes (WDS), paw tremor (PT) and facial myoclonia (FM) in KA-treated rats and significantly delayed the onset time of WDS, from 27 min in the control group to 40 min in the UR group. UR plus GE did not inhibit seizures more effectively than UR alone, but did further prolong the onset time of WDS to 63 min (P < 0.05 vs. UR alone). UR alone reduced the levels of free radicals in vivo, as measured by lipid peroxidation in the brain and luminol-chemiluminescence (CL) counts and lucigenin-CL counts in the peripheral whole blood, but the combination of GE and UR did not reduce free radical levels more markedly than UR alone. In conclusion, our results indicate that UR has anticonvulsive and free radical scavenging activities, and UR combined with GE exhibit greater inhibition on the onset time of WDS than UR alone. These findings suggest that the anticonvulsive effects of UR and GE may be synergistic. However, the mechanism of interaction between UR and GE remains unknown.
Animals↗