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Biomedical subjects

C Y Hsu

Publications and source records attributed to C Y Hsu.

At least 73 records · Page 4Linked to original sources
PubMed2000

Hypertonic mannitol loading of NF-kappaB transcription factor decoys in human brain microvascular endothelial cells blocks upregulation of ICAM-1.

BACKGROUND AND PURPOSE: An acute inflammatory response exacerbates tissue injury during acute ischemic stroke. The transcription factor nuclear factor (NF)-kappaB plays a key role in endothelial cell activation and the inflammatory response. Targeted genetic disruption of NF-kappaB activation in cerebral endothelial cells may be protective in stroke. We determined whether a NF-kappaB transcription factor decoy (TFD) could block intercellular adhesion molecule (ICAM)-1 upregulation, an indicator of endothelial cell activation. METHODS: We modeled ischemia-reperfusion in vitro by exposing cultured human brain microvascular endothelial cells (HBMEC) to tumor necrosis factor (TNF)-alpha and conditions of hypoxia-reoxygenation (H/R). Mannitol was used to load phosphothiorated oligonucleotides containing 3 copies of the kappaB binding sequences (TFDs) into cultured HBMEC. An NF-kappaB TFD, a mutated NF-kappaB TFD, and a scrambled TFD were studied for their effect on ICAM-1 mRNA levels and surface ICAM-1 by ELISA. RESULTS: Hyperosmolar loading with mannitol permitted rapid transfection of TFD into endothelial cell nuclei. The NF-kappaB TFD but not the mutated or scrambled TFD competed with a kappaB sequence for binding to nuclear extracts from HBMEC exposed to TNF-alpha. The NF-kappaB TFD blocked the TNF-alpha-induced and H/R-induced increase in ICAM-1 mRNA levels and the upregulation of surface ICAM-1. CONCLUSIONS: Mannitol delivers phosphothiorated oligonucleotides into cultured HBMEC. An NF-kappaB decoy blocks both TNF-alpha-induced and H/R-induced ICAM-1 upregulation in HBMEC. Targeted genetic disruption of endothelial NF-kappaB activation may be of benefit in acute ischemic stroke.

Cell Hypoxia↗
PubMed2000

Effects of fluid management on edema volume and midline shift in a rat model of ischemic stroke.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the effects of fluid management on brain water content (BW) and midline shift (MLS) after a focal cerebral ischemic insult. METHODS: A suture model was used to induce focal cerebral ischemia for 90 minutes (n=44). The rats were randomly assigned to 3 groups 2. 5 hours after reperfusion: dehydration (n=24), control (n=8), or hydration (n=12). BW was obtained with the wet-dry weight method 24 hours after middle cerebral artery (MCA) occlusion. In addition, MRI were obtained (n=31) 24 hours after the onset of ischemia so that the ratio of hemispheric volumes ipsilateral (IH) and contralateral (CH) to the infarct and the extent of MLS could be obtained. RESULTS: Across the range from moderate dehydration to intravascular volume expansion with isotonic saline, BW of the IH increased linearly as a function of change in body weight (r(2)=0.89), whereas few changes in relation to body weight were observed in CH, indicating a preferential effect of fluid management on the infarcted hemisphere. Furthermore, the hemispheric volume ratio (IH/CH) and MLS also increased in relation to changes in body weight. However, paradoxical increases in BW, IH/CH, and extent of MLS were observed in comparison with controls when severe dehydration was produced with high-dose mannitol. CONCLUSIONS: Changes in ischemic BW by fluid management correlated closely with changes in body weight except when high-dose mannitol was used. Mannitol, as a dehydrating agent, may be associated with bimodal effects, with a high dose aggravating ischemic BW.

Animals↗
PubMed2000

Oxygen-glucose deprivation induces inducible nitric oxide synthase and nitrotyrosine expression in cerebral endothelial cells.

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.

Amino Acid Chloromethyl Ketones↗
PubMed2000

White matter injury in spinal cord ischemia: protection by AMPA/kainate glutamate receptor antagonism.

BACKGROUND AND PURPOSE: Spinal cord ischemia is a serious complication of surgery of the aorta. NMDA receptor activation secondary to ischemia-induced release of glutamate is a major mechanism of neuronal death in gray matter. White matter injury after ischemia results in long-tract dysfunction and disability. The AMPA/kainate receptor mechanism has recently been implicated in white matter injury. METHODS: We studied the effects of AMPA/kainate receptor blockade on ischemic white matter injury in a rat model of spinal cord ischemia. RESULTS: Intrathecal administration of an AMPA/kainate antagonist, 6-nitro-7-sulfamoyl-(f)-quinoxaline-2, 3-dione (NBQX), 1 hour before ischemia reduced locomotor deficit, based on the Basso-Beattie-Bresnahan scale (0=total paralysis; 21=normal) (sham: 21+/-0, n=3; saline: 3.7+/-4.5, n=7; NBQX: 12. 7+/-7.0, n=7, P<0.05) 6 weeks after ischemia. Gray matter damage and neuronal loss in the ventral horn were evident after ischemia, but no difference was noted between the saline and NBQX groups. The extent of white matter injury was quantitatively assessed, based on axonal counts, and was significantly less in the NBQX as compared with the saline group in the ventral (sham: 1063+/-44/200x200 microm, n=3; saline: 556+/-104, n=7; NBQX: 883+/-103, n=7), ventrolateral (sham: 1060+/-135, n=3; saline: 411+/-66, n=7; NBQX: 676+/-122, n=7), and corticospinal tract (sham: 3391+/-219, n=3; saline: 318+/-23, n=7; NBQX: 588+/-103, n=7) in the white matter on day 42. CONCLUSIONS: Results indicate severe white matter injury in the spinal cord after transient ischemia. NBQX, an AMPA/kainate receptor antagonist, reduced ischemia-induced white matter injury and improved locomotor function.

Animals↗
PubMed2000

Functional endoscopic sinus surgery in children and adults.

Functional endoscopic sinus surgery (FESS) has become a popular procedure for the treatment of adults with chronic sinusitis. Recently, it has also been applied in the pediatric population. It has been used to treat chronic sinusitis in our department since April 1988. As of March 1998, 1,112 patients were available for analysis by file and questionnaire review. Of the 1,112 patients, 104 patients (9.4%) who were 16 years of age or younger at the time they first underwent FESS in our department were included in the pediatric endoscopic sinus surgery (PESS) group. The other 1,008 patients (90.6%) were included in the ordinary FESS group. In total, 121 PESS and 1,106 (adult) FESS operations were performed on these patients. Operative complications occurred in 5 PESS operations (4.1%) and 116 FESS operations (10.5%). The postoperative improvement rate was 84% in PESS and 77.1% in FESS. We conclude that PESS can be applied to treat chronic sinusitis effectively in the pediatric population and with less morbidity than FESS.

Adolescent↗
PubMed2000

Effects of low-energy CO2 laser irradiation and the organic matrix on inhibition of enamel demineralization.

In the past two decades, accumulated evidence has clearly demonstrated the inhibitory effects of laser irradiation on enamel demineralization, but the exact mechanisms of these effects remain unclear. The purpose of this study was to investigate the effects of low-energy CO2 laser irradiation on demineralization of both normal human enamel and human enamel with its organic matrix removed. Twenty-four human molars were collected, cleaned, and cut into two halves. One half of each tooth was randomly selected and its lipid and protein content extracted. The other half of each tooth was used as the matched control. Each tooth half had two window areas. All the left windows were treated with a low-energy laser irradiation, whereas the right windows served as the non-laser controls. After caries-like lesion formation in a pH-cycling environment, microradiographs of tooth sections were taken for quantification of demineralization. The mean mineral losses (with standard deviation) of the enamel control, the lased enamel, the non-organic enamel control, and the lased non-organic enamel subgroups were 3955 (1191), 52(49), 4565(1311), and 1191 (940), respectively. A factorial ANOVA showed significant effects of laser irradiation (p = 0.0001), organic matrix (p = 0.0125), and the laser-organic matrix interaction (p = 0.0377). The laser irradiation resulted in a greater than 98% reduction in mineral loss, but the laser effect dropped to about 70% when the organic matrix in the enamel was removed. The results suggest that clinically applicable CO2 laser irradiation may cause an almost complete inhibition of enamel demineralization.

Analysis of Variance↗
PubMed2000

Endoscopic sinus surgery for ethmoid sinus meningioma.

Meningiomas in the ethmoid sinuses are a challenge to manage. A 50-year-old man suffered from a left olfactory groove meningioma. He underwent a bilateral craniotomy to remove the tumor mass in August, 1997. During the follow-up period, a tumor was found in the right posterior ethmoid sinus. Endoscopic sinus surgery was performed to remove the tumor mass in August, 1998. Pathologic examination of the mass revealed a meningioma. No intraoperative or postoperative complications occurred, except for an episode of seizure.

Endoscopy↗
PubMed2000

Open total talar dislocation--report of two cases.

Total dislocation of talus from all its surrounding joints (tibiotalar, subtalar and talonavicular) is an extremely rare injury. Because of its rarity, only few case reports can be found in the literature. In the review of the literature, infection and AVN are the most commonly encountered complications that affect the outcome of these severe injuries. Herein we report two cases of open total talar dislocation. Immediate debridement, reduction of the talus, and primary skin closure was done followed by cast immobilization. After more than 2 years follow up, neither infection nor AVN was found. We conclude that reimplantation of the talus is preferable if the wound is relatively clean. Talectomy, or combined with tibiocalcaneal fusion should be reserved for later salvage procedure.

Adult↗
PubMed1999

Nucleophosmin/B23 regulates the susceptibility of human leukemia HL-60 cells to sodium butyrate-induced apoptosis and inhibition of telomerase activity.

Stable clones of HL-60 cells in which nucleophosmin/B23 was over-expressed or down-regulated were established. The nucleophosmin/B23 protein levels in nucleophosmin/B23 over-expressed (pCR3-B23) or down-regulated (pCR3-32B) cells during BuONa/vanadate-induced apoptosis were characterized as compared with control vector-transfected (pCR3) cells. Over-expression of nucleophosmin/B23 resulted in decreased susceptibility of the cells to BuONa/vanadate-induced apoptosis. The response to inhibition of telomerase activity under BuONa/vanadate treatment also decreased in nucleophosmin/B23 over-expressed (pCR3-B23) cells. On the other hand, down-regulation of nucleophosmin/B23 made the cells more susceptible to BuONa-induced apoptosis or inhibition of telomerase activity. More precisely, by serial dilutions of each extract, the telomerase activity of the cells without drug treatment was determined and was found to be higher in nucleophosmin/B23 over-expressed (pCR3-B23) cells and lower in nucleophosmin/B23 down-regulated (pCR3-32B) cells as compared with the control vector-transfected (pCR3) cells. Our results indicate that nucleophosmin/B23 plays a functional role in the control of cellular apoptosis and immortalization.

Apoptosis↗
PubMed1999

Glucocorticoid receptor expression in the spinal cord after traumatic injury in adult rats.

Methylprednisolone (MP), a glucocorticoid, is the only effective therapeutic agent used in the clinical treatment of acute spinal cord injury (SCI). MP given within 8 hr after SCI significantly improves neurological function. Although the glucocorticoid receptor (GR) is suggested to mediate MP actions, limited knowledge is available on its expression and possible function after SCI. Presently, the expression of GR was studied in a weight-drop SCI model in adult rats. Immunohistochemistry and Western blot analysis revealed an increase in GR protein expression as early as 15 min after injury. GR expression sharply increased at 4 hr (22-fold), peaked at 8 hr (56-fold), rapidly declined at 1 d, and returned to the baseline level at and after 3 d. During its peak expression, GR was localized in neural somata and dendrites but not in axons and their terminals. GR immunoreactivity was also found in oligodendrocytes and astrocytes. Interestingly, other cell types, such as endothelial cells, were GR-negative. An increase in the binding activity of nuclear proteins to the glucocorticoid responsive element was also observed after SCI, demonstrating a functional element of GR activation. Finally, colocalization of GR and tumor necrosis factor alpha (TNF-alpha), an inflammatory cytokine, was observed in neurons and glial cells, consistent with MP regulation of TNF-alpha in this model. Thus, the transient expression of high levels of GR after SCI may provide new insights into the anti-inflammatory action of MP.

Animals↗
PubMed1999

Pyrithione, a zinc ionophore, inhibits NF-kappaB activation.

Pyrrolidine dithiocarbamate (PDTC) suppresses NF-kappaB activity and exhibits cytotoxic effects in bovine cerebral endothelial cells (BCECs), and we have previously reported that these PDTC effects were accompanied by an increase in intracellular zinc levels. To further explore the role of zinc in the modulation of NF-kappaB activation, we studied the effect of pyrithione, a zinc ionophore, on NF-kappaB activation in BCECs. Pyrithione inhibited NF-kappaB activity in a time- and dose-dependent manner. Ca-EDTA, but not Zn-EDTA, prevented pyrithione inhibition of NF-kappaB activity. Pyrithione increased the intracellular zinc level within 15 min. This effect was also abolished by Ca-EDTA, but not by Zn-EDTA. The potency of pyrithione on NF-kappaB inhibition and zinc influx was approximately one order of magnitude more potent than PDTC. These findings establish the regulatory role of intracellular zinc levels on NF-kappaB activity in BCECs.

Animals↗
PubMed1999

Berberine-induced apoptosis of human leukemia HL-60 cells is associated with down-regulation of nucleophosmin/B23 and telomerase activity.

The steady-state level of nucleophosmin/B23 mRNA decreased during berberine-induced (25 microg/ml, 24 to 96 hr) apoptosis of human leukemia HL-60 cells. A decline in telomerase activity was also observed in HL-60 cells treated with berberine. A stable clone of nucleophosmin/B23 overexpressed in HL-60 cells was selected and found to be less responsive to berberine-induced apoptosis. About 35% to 63% of control vector-transfected cells (pCR3) exhibited morphological characteristics of apoptosis, while about 8% to 45% of nucleophosmin/B23-over-expressed cells (pCR3-B23) became apoptotic after incubation with 15 microg/ml berberine for 48 to 96 hr. DNA extracted from pCR3 cells contained more fragmented DNA than pCR3-B23 cells during treatment with 15 microg/ml berberine for 24 to 48 hr. Our results indicate that berberine-induced apoptosis is associated with down-regulation of nucleophosmin/B23 and telomerase activity. We also suggest that nucleophosmin/B23 may play an important role in the control of the cellular response to apoptosis induction.

Apoptosis↗
PubMed1999

Zinc is required in pyrrolidine dithiocarbamate inhibition of NF-kappaB activation.

Pyrrolidine dithiocarbamate (PDTC) is a potent inhibitor of nuclear factor kappa B (NF-kappaB) activation. PDTC inhibited basal NF-kappaB activity of endothelial cells. PDTC, however, failed to inhibit basal NF-kappaB activity after withdrawal of serum in the media, and the inhibitory effect of PDTC could be restored by addition of zinc. When various preparations of metal ion-EDTA were tested with PDTC in serum-containing media, only Zn-EDTA failed to block the inhibitory effect of PDTC. The dependence on zinc was also noted in PDTC inhibition of NF-kappaB stimulated by TNF alpha. These facts suggest that zinc is required for PDTC inhibition of NF-kappaB activation.

Animals↗
PubMed1999

High rate of clinical complete response to weekly outpatient neoadjuvant chemotherapy in oral carcinoma patients using a new regimen of cisplatin, 5-fluorouracil, and bleomycin alternating with methotrexate and epirubicin.

BACKGROUND: A Phase II trial was initiated to evaluate the response to and toxicity of a new regimen of weekly outpatient neoadjuvant chemotherapy in patients with oral carcinoma. METHODS: Patients with previously untreated squamous cell carcinoma of the oral cavity were eligible for this trial. The neoadjuvant chemotherapy was comprised of cisplatin, 25 mg/m2, 5-fluorouracil, 1000 mg/m2, and bleomycin, 10 mg/m2, mixed in normal saline as a 24-hour intravenous (i.v.) infusion, alternating with methotrexate, 30 mg/m2, and epirubicin, 30 mg/m2, as an i.v. bolus (PFB/ME) on a weekly schedule for 8-12 weeks. In patients with American Joint Committee on Cancer Stage IV disease who completed neoadjuvant chemotherapy, surgery was preferred to radiotherapy, unless patients refused surgery. RESULTS: A total of 40 patients (82.5% with Stage IV disease) with previously untreated oral carcinoma were enrolled. The median size of the primary tumor was 7 cm (range, 3-13 cm). Fifty percent of patients had tumor penetrating through the oral mucosa to the cheek skin and 62.5% had bony destruction. Detectable cervical lymph nodes were noted in 77.5% of patients. After neoadjuvant weekly chemotherapy, 22 patients (55%) showed complete response (CR) and 15 patients (37.5%) showed partial response, for an overall response rate of 92.5%. World Health Organization Grade 3/4 toxicity included mucositis (7.5%), leukopenia (25%), anemia (10%), and thrombocytopenia (2.5%). Eleven of 33 patients with Stage IV disease underwent surgery, and pathologic CR (2 patients) or microscopic residual tumor (4 patients) was noted (54.5%). CONCLUSIONS: The results of the current study indicate that a weekly PFB/ME neoadjuvant chemotherapy regimen is highly effective for the treatment of patients with oral carcinoma. In addition, this regimen has low toxicity. The authors believe that implementation of this regimen into a multimodality therapy protocol deserves further study.

Adult↗
PubMed1999

Suppression of postischemic hippocampal nerve growth factor expression by a c-fos antisense oligodeoxynucleotide.

We examined the uptake and distribution of an antisense phosphorothioated oligodeoxynucleotide (s-ODN) to c-fos, rncfosr115, infused into the left cerebral ventricle of male Long-Evans rats and the effect of this s-ODN on subsequent Fos, NGF, neurotrophin-3 (NT-3), and actin expression. To establish the uptake and turnover of s-ODN in the brain, we studied the copurification of the immunoreactivity of biotin with biotinylated s-ODN that was recovered from different regions of the brain. A time-dependent diffusion and the localization of s-ODN were further demonstrated by labeling the 3'-OH terminus of s-ODN in situ with digoxigenin-dUTP using terminal transferase and detection using anti-digoxigenin IgG-FITC. Cellular uptake of the s-ODN was evident in both the hippocampal and cortical regions, consistent with a gradient originating at the ventricular surface. Degradation of the s-ODN was observed beginning 48 hr after delivery. The effectiveness of c-fos antisense s-ODN was demonstrated by its suppression of postischemic Fos expression, which was accompanied by an inhibition of ischemia-induced NGF mRNA expression in the dentate gyrus. Infusion of saline, the sense s-ODN, or a mismatch antisense s-ODN did not suppress Fos expression. That this effect of c-fos antisense s-ODN was specific to NGF was demonstrated by its lack of effect on the postischemic expression of the NT-3 and beta-actin genes. Our results demonstrate that c-fos antisense s-ODN blocks selected downstream events and support the contention that postischemic Fos regulates the subsequent expression of the NGF gene and that Fos expression may have a functional component in neuroregeneration after focal cerebral ischemia-reperfusion.

Actins↗
PubMed1999

Injection therapy for stress incontinence in women.

Periurethral bulking agents have been used to treat intrinsic sphincter deficiency for decades. Currently available agents include polytetrafluoroethylene, glutaraldehyde cross-linked collagen, autologous fat and silicone microimplants. Polytetrafluoroethylene has never been approved by the United States Food and Drug Administration for periurethral injection because of the risk of particle migration. Early results have reported subjective cure rates of up to 95% with collagen injections. However, collagen may cause allergic reactions and long-term results are still awaited. Periurethral fat injection has a reported success rate ranging from 23% to 65%. It is simple and avoids the use of foreign materials, but the main disadvantage relates to the variability of resorption and connective tissue replacement. Silicone microimplants need further study to evaluate their efficacy and safety. The best material has not yet been defined. Long-term studies are still necessary to define the optimal injectable agent.

Adipose Tissue↗
PubMed1999

Bacteriology of endoscopically normal maxillary sinuses.

The bacteriology of maxillary sinuses with normal endoscopic findings is reported in this study. When transantral sinoscopy was used to examine the maxillary sinuses, the whole maxillary sinus was inspected with different-angle endoscopes. If no lesion was seen over the whole maxillary sinus mucosa, no secretion existed in the maxillary sinus cavity, and the maxillary sinus ostium was wide open, the maxillary sinus was considered endoscopically normal. The bacteriology of these endoscopically normal maxillary sinuses was studied by passing cotton-tipped sticks through the cannula to collect swab specimens. In some cases, a biopsy forceps was also passed to obtain mucosal specimens. The specimens were sent to the laboratory for aerobic and anaerobic cultures. Between July 1990 and May 1998, 83 swab and 31 mucosal specimens were collected from 69 patients who had not taken any antibiotic within 10 days before endoscopy. The culture rates were 62.3 per cent (35/53) from swab specimens and 57.1 per cent (eight out of 14) from mucosal specimens in patients with the diagnosis of chronic paranasal sinusitis, and were 46.7 per cent (14/30) from swab specimens and 41.2 per cent (seven out of 17) from mucosal specimens in patients without this diagnosis. This study shows that endoscopically normal maxillary sinuses are not sterile.

Adolescent↗