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Biomedical subjects

C H Hsieh

Publications and source records attributed to C H Hsieh.

At least 19 recordsLinked to original sources
PubMed2006

A high yield robotic synthesis of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) and 9-[3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine([18F] FHPG) for gene expression imaging.

The aim of this study was to develop an automated synthesis of 9-(4-[(18)F]-fluoro-3-hydroxymethylbutyl)guanine ([(18)F]FHBG) and 9-[(3-[(18)F]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([(18)F]FHPG) using a Scanditronix Anatech RB III robotic system. [(18)F]HF was produced via (18)O(p, n)(18)F using a Scanditronix MC17F cyclotron. On average, a typical run produced [(18)F]FHBG and [(18)F]FHPG with an uncorrected radiochemical yield of 19% and 16%, respectively, at end of synthesis (EOS) from irradiation of 95% enriched [(18)O]water. The total synthesis time was 80 min. The retention time of [(18)F]FHBG and [(18)F]FHPG (the radio-peak) was 3.9 and 4.0 min, respectively, which was consistent with the [(19)F]FHBG and [(19)F]FHPG ultraviolet peak. The radiochemical purity was greater than 97%. A robotic, automated method for [(18)F]FHBG and [(18)F]FHPG radiosynthesis is therefore feasible. The radiation burden for the operator can be reduced as much as possible. Sufficient radioactivities of [(18)F]FHBG and [(18)F]FHPG could be obtained for non-invasive monitoring the expression of transfected gene in vivo with positron emission tomography (PET).

Equipment Design↗
PubMed2005

A simple model for quantification of the radiobiological effectiveness of the 10B(n,alpha)7Li capture reaction in BNCT.

A simple model has been developed for predicting radiobiological effectiveness of the neutron capture reaction in boron neutron capture therapy. This model was derived from the relationship between the cell survival from the boron capture reaction, the intracellular boron concentration, and the thermal neutron fluence. We found that the cell-killing effect of the boron capture reaction was well described using a power function of the intracellular boron concentration. Hence the relationship between cell survival from the boron capture reaction, intracellular boron concentration, and the thermal neutron fluence could be determined using a simple mathematical equation. We consider that our current approach is more appropriate and realistic than the conventional theoretical mathematical model used to estimate the radiobiological effectiveness of the neutron capture reaction in boron neutron capture therapy.

Animals↗
PubMed2005

Distally based sural island flap for the reconstruction of a large soft tissue defect in an open tibial fracture with occluded anterior and posterior tibial arteries-a case report.

To repair a 10 x 16 cm soft tissue defect of right lower leg that accompanied with occluded anterior and posterior tibial arteries in a 30-year-old man who sustained comminuted type III(B) Gustilo open tibial and fibular fracture, we present a successful reconstruction by using a large distally based sural island flap perfused by the lowermost perforator of the peroneal artery. This flap is a useful alternative for distal extremity reconstruction when anterior and posterior tibial arteries are occluded, as large flaps can be elevated safely based on only one peroneal perforator.

Adult↗
PubMed2005

Effect of celecoxib on Ca2+ fluxes and proliferation in MDCK renal tubular cells.

The effect of celecoxib on renal tubular cells is largely unexplored. In Madin Darby canine kidney (MDCK) cells, the effect of celecoxib on intracellular CaCa2+ concentration ([Ca2+]i) and proliferation was examined by using the Ca(2 +)-sensitive fluorescent dye fura-2 and the viability detecting fluorescent dye tetrazolium, respectively. Celecoxib (> or =1 micro M) caused an increase of [CaCa2+]i in a concentration-dependent manner. Celecoxib-induced [CaCa2+]i increase was partly reduced by removal of extracellular CaCa2+. Celecoxib-induced CaCa2+ influx was independently suggested by MnCa2+ influx-induced fura-2 fluorescence quench. In Ca(2 +)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2 +)-ATPase, caused a monophasic [CaCa2+]i increase, after which celecoxib only induced a tiny [CaCa2+]i increase; conversely, pretreatment with celecoxib completely inhibited thapsigargin-induced [CaCa2+]i increases. U73122, an inhibitor of phospholipase C, abolished ATP (but not celecoxib)-induced [CaCa2+]i increases. Overnight incubation with 1 or 10 micro M celecoxib decreased cell viability by 80% and 100%, respectively. These data indicate that celecoxib evokes a [CaCa2+]i increase in renal tubular cells by stimulating both extracellular CaCa2+ influx and intracellular CaCa2+ release and is highly toxic to renal tubular cells in vitro.

Animals↗
PubMed2005

Econazole induces increases in free intracellular Ca2+ concentrations in human osteosarcoma cells.

Econazole is an antifungal drug with different in vitro effects. However, econazole's effect on osteoblast-like cells is unknown. In human MG63 osteosarcoma cells, the effect of econazole on intracellular Ca2+ concentrations ([Ca2+]i) was explored by using fura-2. At a concentration of 0.1 microM, econazole started to cause a rise in [Ca2+]i in a concentration-dependent manner. Econazole-induced [Ca2+]i rise was reduced by 74% by removal of extracellular Ca2+. The econazole-induced Ca2+ influx was mediated via a nimodipine-sensitive pathway. In Ca2+ -free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca+ -ATPase, caused a [Ca2+]i rise, after which the increasing effect of econazole on [Ca2+]i was abolished. Pretreatment of cells with econazole to deplete Ca2+ stores totally prevented thapsigargin from releasing Ca2+. U73122, an inhibitor of phospholipase C, abolished histamine (an inositol 1,4,5-trisphosphate-dependent Ca2+ mobilizer)-induced, but not econazole-induced, [Ca2+]i rise. Econazole inhibited 76% of thapsigargin-induced store-operated Ca2+ entry. These findings suggest that in MG63 osteosarcoma cells, econazole increases [Ca2+]i by stimulating Ca2+ influx and Ca2+ release from the endoplasmic reticulum via a phospholipase C-independent manner. In contrast, econazole acts as a potent blocker of store-operated Ca2+ entry.

Antifungal Agents↗
PubMed2005

Multiple-event study of bioretention for treatment of urban storm water runoff.

Bioretention is a novel best management practice for urban storm water, employed to minimize the impact of urban runoff during storm events. Bioretention consists of porous media layers that can remove pollutants from infiltrating runoff via mechanisms that include adsorption, precipitation, and filtration. However, the effectiveness of bioretention in treating repetitive inputs of runoff has not been investigated. In this study, a bioretention test column was set up and experiments proceeded once every week for a total of 12 tests. Through all 12 repetitions, the infiltration rate remained constant (0.35 cm/min). All 12 tests demonstrated excellent removal efficiency for TSS, oil/grease, and lead (99%). For total phosphorus, the removal efficiency was about 47% the system removal efficiency ranged from 2.3% to 23%. Effluent nitrate concentration became higher than the influent concentration during the first 28 days and removal efficiency ranged from 9% to 20% afterward. Some degree of denitrification was apparently proceeding in the bioretention system. Overall, the top mulch layer filtered most of TSS in the runoff and prevented the bioretention media from clogging during 12 repetitions. Runoff quality was improved by the bioretention column.

Adsorption↗
PubMed2003

The effect of surgical stress on insulin sensitivity, glucose effectiveness and acute insulin response to glucose load.

Hyperglycemia after stress is a very common clinical phenomenon. It is generally hypothesized that the underlying cause is a neuroendocrine-mediated deterioration in glucose metabolism. However, the detailed roles of insulin sensitivity, glucose effectiveness and acute insulin response to glucose load in response to stress have not been well established. Hernioplasty was used as a minor stress model for studying stress-induced hyperglycemia. Eleven healthy young men were enrolled voluntarily in this study. Their mean age was 22.0 +/- 0.9 yr and BMI 23.3 +/- 0.6 kg/m2. Frequently sampled i.v. glucose tolerance tests were performed one day before and one day after the surgery. Insulin sensitivity (SI), glucose effectiveness (EG) and area under acute insulin response (AIR) were calculated from "minimal model" algorithms. We also measured fasting concentrations of human GH, ACTH and F on the days of the test. Compared to the pre-operation data, levels of ACTH and F did not change significantly after the surgery. Only GH levels were marginally significant. On the other hand, the SI (0.75 +/- 0.1, 0.52 +/- 0.9 x 10(-5) min(-1)/pmol, p = 0.04), EG (0.023 +/- 0.03, 0.016 +/- 0.003 min(-1), p = 0.01) and AIR (6738.5 +/- 1111.6, 5130.0 +/- 1047.2 pmol, p = 0.005) were all significantly decreased after surgery. The percentages of decrease were 16.3 +/- 15.5, 32.1 +/- 10.3 and 17.8 +/- 10.3%, respectively. Finally, only the changes of EG positively correlate with the changes of ACTH before and after surgery. No significant changes were noted among other stress hormones and the changes of SI, EG and AIR. In conclusion, hernioplasty results in reduced SI, EG and AIR. Among them, although not statistically significant, the EG showed the most distinct decrease after the surgery, which has not been found in previous literature.

Adolescent↗
PubMed2002

Geometric and statistical properties of the mean-field hydrophobic-polar model, the large-small model, and real protein sequences.

Lattice models, for their coarse-grained nature, are best suited for the study of the "designability problem," the phenomenon in which most of the about 16 000 proteins of known structure have their native conformations concentrated in a relatively small number of about 500 topological classes of conformations. Here it is shown that on a lattice the most highly designable simulated protein structures are those that have the largest number of surface-core switchbacks. A combination of physical, mathematical, and biological reasons that causes the phenomenon is given. By comparing the most foldable model peptides with protein sequences in the Protein Data Bank, it is shown that whereas different models may yield similar designabilities, predicted foldable peptides will simulate natural proteins only when the model incorporates the correct physics and biology, in this case if the main folding force arises from the differing hydrophobicity of the residues, but does not originate, say, from the steric hindrance effect caused by the differing sizes of the residues.

Amino Acid Sequence↗
PubMed2001

Three-dimensional mapping of brain neuropils in the cockroach, Diploptera punctata.

Herein, we present a complete three-dimensional (3D) map of major neuropil structures in the central brain of the cockroach Diploptera punctata. The positions of the structures have been ascertained by confocal microscopy, which, until now-for reasons of tissue opacity and nonhomogeneity-has been thought impractical in imaging fluorescently labeled structures thicker than 150 microm. In this report, however, we have used digestive enzymes and microwave-aided fixation to stain, clear, and optically section, in its entirety, an intact central brain more than 500 microm thick. The central brain from an adult female cockroach was stained thoroughly with the membrane probe NBD-ceramide and the DNA probe propidium iodide. The central brain as well as such neuropil regions as mushroom bodies, central complex, antennal glomeruli, and lobus glomerulati were individually outlined, segmented, and reconstructed in three dimensions to a spatial resolution of approximately 1 microm in the X-Y plane and 3 microm in the Z plane. The volume and surface area of each neuropil compartment were determined, and Kenyon cells of the mushroom bodies were counted. We determined that each brain hemisphere contains about 230,000 Kenyon cells, 99 antennal lobe glomeruli, and 40 lobus glomerulatus glomeruli. Segmented compartments were assigned as separate channels and merged into a single data base to reconstruct a 3D central brain containing eight different channels. This is the first 3D map at submicron resolution of an entire animal's brain that measures more than 500 microm in thickness.

Animals↗
PubMed2001

Reoperative Snodgrass procedure.

PURPOSE: We examine the results of a reoperative Snodgrass procedure for complex hypospadias. MATERIALS AND METHODS: A total of 25 patients with hypospadias in whom repair had failed underwent a reoperative Snodgrass procedure. Mean patient age and number of prior repairs were 11.4 years and 2.5, respectively. Before this treatment the meatus was at the distal shaft in 10 cases, mid shaft in 9, proximal shaft in 4 and penoscrotal junction in 2. Preoperatively the associated complications were fistulas in 13 patients, residual chordee in 12 and diverticulum in 1. In 8 cases the fistula was incorporated into the hypospadiac opening and treated as a longer defect. The urethral plates were, subjectively, surgically altered or unaltered in 7 and 18 patients, respectively. In 8 patients (group A) the previous repair(s) did not involve dissection of the urethral plate (unaltered) nor was there a fistula. The remaining 17 patients were classified as group B. The neourethra was then reconstructed as the Snodgrass technique. Followup urethral calibration was performed in 17 patients. RESULTS: Mean followup period was 13.7 months. Mean length and size of neourethra were 19.9 mm. and 14Fr, respectively. There were 7 (28%) postoperative fistulas of the neourethra. The incidences of postoperative fistula of the neourethra were 0% and 41.2% in groups A and B, respectively (p <0.01). Statistically the surgically altered urethral plate and the presence of a preoperative fistula were 2 independent factors predicting a higher postoperative fistula rate. The overall postoperative meatal stenosis rate was 13 (52%) with 3 (37.5%) in group A and 10 (58.8%) in group B, respectively (p >0.05). The meatal stenosis was treated with simple dilation in 11 cases and meatoplasty during subsequent fistula repair in 2. Stricture at the anastomostic site between the normal urethra and neourethra was noted in 2 patients. Fistula repair was successfully performed 6 months later in 4 patients. CONCLUSIONS: The Snodgrass procedure is a viable option for the treatment of previously failed hypospadias repair. It was highly effective in patients with a surgically unaltered urethral plate and no preoperative fistula.

Adolescent↗
PubMed2000

Tyr115, gln165 and trp209 contribute to the 1, 2-epoxy-3-(p-nitrophenoxy)propane-conjugating activity of glutathione S-transferase cGSTM1-1.

We investigated the epoxidase activity of a class mu glutathione S-transferase (cGSTM1-1), using 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) as substrate. Trp209 on the C-terminal tail, Arg107 on the alpha4 helix, Asp161 and Gln165 on the alpha6 helix of cGSTM1-1 were selected for mutagenesis and kinetic studies. A hydrophobic side-chain at residue 209 is needed for the epoxidase activity of cGSTM1-1. Replacing Trp209 with histidine, isoleucine or proline resulted in a fivefold to 28-fold decrease in the k(cat)(app) of the enzyme, while a modest 25 % decrease in the k(cat)(app) was observed for the W209F mutant. The rGSTM1-1 enzyme has serine at the correponding position. The k(cat)(app) of the S209W mutant is 2. 5-fold higher than that of the wild-type rGSTM1-1. A charged residue is needed at position 107 of cGSTM1-1. The K(m)(app)(GSH) of the R107L mutant is 38-fold lower than that of the wild-type enzyme. On the contrary, the R107E mutant has a K(m)(app)(GSH) and a k(cat)(app) that are 11-fold and 35 % lower than those of the wild-type cGSTM1-1. The substitutions of Gln165 with Glu or Leu have minimal effect on the affinity of the mutants towards GSH or EPNP. However, a discernible reduction in k(cat)(app) was observed. Asp161 is involved in maintaining the structural integrity of the enzyme. The K(m)(app)(GSH) of the D161L mutant is 616-fold higher than that of the wild-type enzyme. In the hydrogen/deuterium exchange experiments, this mutant has the highest level of deuteration among all the proteins tested. We also elucidated the structure of cGSTM1-1 co-crystallized with the glutathionyl-conjugated 1, 2-epoxy-3-(p-nitrophenoxy)propane (EPNP) at 2.8 A resolution. The product found in the active site was 1-hydroxy-2-(S-glutathionyl)-3-(p-nitrophenoxy)propane, instead of the conventional 2-hydroxy isomer. The EPNP moiety orients towards Arg107 and Gln165 in dimer AB, and protrudes into a hydrophobic region formed by the loop connecting beta1 and alpha1 and part of the C-terminal tail in dimer CD. The phenoxyl ring forms strong ring stacking with the Trp209 side-chain in dimer CD. We hypothesize that these two conformations represent the EPNP moiety close to the initial and final stages of the reaction mechanism, respectively.

Amino Acid Substitution↗
PubMed2000

Mean-field HP model, designability and alpha-helices in protein structures.

Analysis of the geometric properties of a mean-field HP model on a square lattice for protein structure shows that structures with a large number of switchbacks between surface and core sites are chosen favorably by peptides as unique ground states. Global comparison of model (binary) peptide sequences with concatenated (binary) protein sequences listed in the Protein Data Bank and the Dali Domain Dictionary indicates that the highest correlation occurs between model peptides choosing the favored structures and those portions of protein sequences containing alpha helices.

Computer Simulation↗
PubMed2000

Sequence variants and functional analysis of human papillomavirus type 16 E5 gene in clinical specimens.

Previously, we found that the E5 protein can be expressed in HPV-16 infected precancerous lesions and cervical cancer. In this study, we investigated the presence of sequence variants of E5 in HPV-16 infected tissues. Toward this end, we amplified the E5 gene by polymerase chain reaction from 29 HPV-16 infected tissues including eight normal tissues, seven high grade neoplastic tissues (high grade squamous intraepithelial lesions (HSIL) and 14 cervical cancer tissues. Sequence analysis demonstrated that there were three mutational hot spots at positions 3979, 4042, and 4077 of the HPV-16 DNA; these and other mutations resulted in six variants in the E5 sequence. This resulted in four E5 protein mutants, named WTE5 [wild type E5 protein], 14E5, 21E5 and 56E5. Functional analysis of these four mutant proteins revealed that the transforming activities of 14E5, 21E5 and 56E5 were 0.95, 0.59, and 0.89 fold of WTE5, respectively. Although E5 was expressed in all of the HSIL and cervical cancer tissues, but in only one of the eight normal tissues tested, only WT E5 protein was found in HSIL while in cervical cancer tissues both WT and mutant E5 proteins were detected. Since these E5 proteins exhibited the same in vitro transforming activity, these data suggest that expression of E5 is important in development and progression toward malignancy but mutation of E5 does not affect the transformation process.

Base Sequence↗
PubMed2000

Tubularized incised plate urethroplasty for proximal hypospadias.

OBJECTIVE: To review our experience of using the tubularized incised plate (TIP) urethroplasty (useful in the treatment of distal hypospadias) to treat proximal hypospadias. MATERIALS AND METHODS: From March 1997 to March 2000 primary repairs were carried out on 40 boys (mean age 4.5 years) with proximal hypospadias. After degloving the penile skin the meatus was at the mid-shaft in 10 boys, at the proximal penile shaft in 11, at the penoscrotal junction in 16, at the scrotum in two and at the perineum in one. The 21 patients with a mid or proximal shaft meatus were categorized as having mid-shaft and the other 19 as having posterior hypospadias. Tunica albuginea plication (TAP) was used to correct residual ventral curvature. The method of urethroplasty was adapted from that described by Snodgrass. The key step of the TIP repair is a midline incision of the urethral plate; a subcutaneous tissue flap dissected from the inner prepuce is used to cover the neourethra. An 8 or 10 F nasogastric tube is used as a urethral stent and removed 7 or 8 days after surgery. Follow-up endoscopy and urethral sounding were carried out in 17 of the patients aged < 6 years; the mean follow-up was 12.5 months. RESULTS: TAP was used to correct penile curvature in nine (23%) of the patients. Excluding stenosis, the TIP repair was successful in 20 (90%) of those with mid-shaft and in 16 of the 19 with posterior hypospadias; for all complications the respective rates were 19 of 22 and 15 of 19. The overall success rate was 88% for all 40 patients with proximal hypospadias; a urethrocutaneous fistula occurred in two of those with mid-shaft and three of those with posterior hypospadias. Urethral meatal stenosis occurred in four (12%) of the patients (two in each group); two were associated with a fistula and the other two had only mild meatal stenosis. The overall complication rate was 17.5% (three and four in the mid and the posterior hypospadias groups, respectively). The meatal stenosis was managed by simple dilatation in three and meatoplasty in one patient. Endoscopically, the mucosa of neourethra was pink and smooth in all 17 patients assessed. The calibre of all 17 neourethra was > or = 8 F and in 13 was > or = 10 F. CONCLUSION: TIP repair is a reliable method for treating both mid-shaft and posterior hypospadias.

Child, Preschool↗
PubMed2000

Induction of CD8 T cells by vaccination with recombinant adenovirus expressing human papillomavirus type 16 E5 gene reduces tumor growth.

The potential of the E5 protein as a tumor vaccine candidate has not been explored yet. In this study, we evaluate the human papillomavirus type 16 (HPV-16) E5 protein delivered by an adenovirus vector as a tumor vaccine for cervical lesions. The results demonstrate that a single intramuscular injection of a recombinant adenovirus carrying the HPV-16 E5 gene into syngeneic animals can reduce the growth of tumors which contain E5 gene expression. Moreover, the E5 vaccine-induced tumor protection occurs through CD8 T cells but not through CD4 T cells in in vitro assays. In addition, our studies using knockout mice with distinct T-cell deficiencies confirm that cytotoxic T-lymphocyte-induced tumor protection is CD8 dependent but CD4 independent. Hence, HPV-16 E5 can be regarded as a tumor rejection antigen.

Adenoviridae↗
PubMed2000

Use of extracorporeal membrane oxygenation to rescue a child with acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) carries a high mortality of about 60%. The results of conventional treatments for ARDS are poor. We report the use of extracorporeal membrane oxygenation (ECMO) to rescue a child with ARDS. The patient, a 7-year-old boy, underwent a Ross procedure and mitral valvuloplasty because of severe aortic and mild mitral regurgitation. ARDS due to massive transfusion and prolonged cardiopulmonary bypass developed in the early postoperative period. Hypoxemia persisted despite conventional treatments, including pressure-controlled ventilation and high-frequency ventilation. Finally, venovenous ECMO was used to rescue the patient. With ECMO support, gas exchange was well maintained with a lower ventilator setting, and ventilator-induced lung injuries were avoided. ECMO was used for 183 hours, at which point the boy was weaned without complications. His recovery was uneventful. At the latest follow-up, 6 months after the operation, he was in New York Heart Association function class I and had no complaints of lung disease. This case suggests that venovenous ECMO can be a rescue method for patients with ARDS that is refractory to conventional treatments.

Child↗