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Biomedical subjects

M H Hsu

Publications and source records attributed to M H Hsu.

At least 19 recordsLinked to original sources

An integrated inundation model for highly developed urban areas.

A numerical model is developed in this study with various components for simulating the complex flow phenomena in urban drainage basins. The model integrates the HEC-1 model, a 1-D dynamic channel-flow model, a 2-D non-inertia overland-flow model and the SWMM model to reflect the hydraulic processes in areas with different characteristics. The inundation of underground infrastructure during flood is also considered in the model. The typhoon Nari event in 2001, which resulted in severe flood in downtown Taipei, is simulated by the model. The result is compared with the survey records of flooded areas, which reveals the storage effect of underground infrastrucures is significant to the simulation results of highly developed urban areas.

Cities↗

Predicting cranial computed tomography results of head injury patients using an artificial neural network.

We conducted this study to determine if artificial neural network modeling would predict cranial computed tomography results in head injury patients using different combinations of clinical variables. 150 consecutive patients admitted to a regional trauma center with head injury were enrolled in the study. The CT was labeled with presence of surgically significant intracranial hematoma (SSIH), if midline shift, obliteration of ambient cistern or basal cistern were found. The best performance of our models to differentiate normal from abnormal cranial CT and detection of SSIH was ideal.

Craniocerebral Trauma↗

Consumption of flea faeces and eggs by larvae of the cat flea, Ctenocephalides felis.

The effects of the consumption of flea faeces and non-viable eggs on larval development in the cat flea Ctenocephalides felis (Bouché) (Siphonaptera: Pulicidae) were investigated. Only 13.3% of larvae developed into adults when fed a diet of male or female flea faeces alone; however, 90% of larvae developed into adults when fed on flea faeces supplemented with non-viable flea eggs. When fed with non-viable eggs alone, larvae did not develop into adults. Nevertheless, non-viable eggs may provide critical supplemental nutrients, lacking in flea faeces and required for larval development. None of the larvae fed on flea faeces or non-viable eggs alone formed a cocoon. A diet of flea faeces alone significantly extended the second as well as third larval stadia compared to larvae fed on diets containing non-viable eggs. It is suggested that the cannibalism of fertile eggs may limit population growth in the cat flea.

Animals↗

Identification of peroxisome proliferator-responsive human genes by elevated expression of the peroxisome proliferator-activated receptor alpha in HepG2 cells.

In mice and other sensitive species, PPARalpha mediates the induction of mitochondrial, microsomal, and peroxisomal fatty acid oxidation, peroxisome proliferation, liver enlargement, and tumors by peroxisome proliferators. In order to identify PPARalpha-responsive human genes, HepG2 cells were engineered to express PPARalpha at concentrations similar to mouse liver. This resulted in the dramatic induction of mRNAs encoding the mitochondrial HMG-CoA synthase and increases in fatty acyl-CoA synthetase (3-8-fold) and carnitine palmitoyl-CoA transferase IA (2-4-fold) mRNAs that were dependent on PPARalpha expression and enhanced by exposure to the PPARalpha agonist Wy14643. A PPAR response element was identified in the proximal promoter of the human HMG-CoA synthase gene that is functional in its native context. These data suggest that humans retain a capacity for PPARalpha regulation of mitochondrial fatty acid oxidation and ketogenesis. Human liver is refractory to peroxisome proliferation, and increased expression of mRNAs for the peroxisomal fatty acyl-CoA oxidase, bifunctional enzyme, or thiolase, which accompanies peroxisome proliferation in responsive species, was not evident following Wy14643 treatment of cells expressing elevated levels of PPARalpha. Additionally, no significant differences were seen for the expression of apolipoprotein AI, AII, or CIII; medium chain acyl-CoA dehydrogenase; or stearoyl-CoA desaturase mRNAs.

Acyl Coenzyme A↗

Sonographic features of xanthogranulomatous pyelonephritis.

PURPOSE: The purpose of this study was to describe the various sonographic features of xanthogranulomatous pyelonephritis (XGP). METHODS: We retrospectively reviewed the CT, sonographic, and medical records of patients diagnosed with XGP from January 1981 to December 1998. Twenty-seven patients for whom XGP was histopathologically confirmed were included in the study. There were 12 men and 15 women, with an age range of 21-86 years (mean, 57 years). All patients had undergone sonography of the kidneys. The renal size, shape, and outline were recorded. The presence of perinephric fluid accumulation, of obstructive uropathy, or of internal echoes in the dilated collecting system and the echotexture of the renal parenchyma were documented. RESULTS: We categorized the XGP into 4 groups on the basis of the sonographic features: (1) diffuse hydronephrotic, 12 patients (44%); (2) diffuse parenchymal, 9 patients (33%); (3) diffuse contracted, 4 patients (15%); and (4) segmental or focal, 2 patients (7%). A localized perinephric fluid collection was present in 4 patients (15%). The preoperative sonographic diagnoses were pyonephrosis (n = 14, 52%), renal pelvic tumor with possible associated infection (n = 5, 19%), renal parenchymal mass (n = 2, 7%), hydronephrosis (n = 2, 7%), and chronic pyelonephritis with renal atrophy (n = 4, 15%). XGP was considered a possible diagnosis in only 11 patients (41%). CONCLUSIONS: XGP has no specific sonographic features but is suggested by parenchymal thinning and hydronephrosis, sonographic signs of chronic obstructive uropathy caused by stones; echoes in the dilated collecting system; and a perinephric fluid collection. CT, needle biopsy, or both are recommended to further evaluate and confirm sonographically suspected XGP.

Adult↗

A modeling study of water quality in main channel and estuarine wetland.

A simple computation framework is applied to include estuarine wetland and their interaction with main channels in estuarine modeling. The concept and the model implementation of the scheme are explained using a vertical two-dimensional model of estuarine hydrodynamics and water quality. The model was applied to the Tanshui River estuary and Kuan-Du wetland. The model is calibrated and verified by the available measured data. Simulations are also conducted for various upstream freshwater discharges to predict water quality in the main channel and estuarine wetland. The results show that the inclusion of estuarine wetland in a water-quality model not only provides a framework for computing water-quality conditions but also accounts for the interaction between wetland and main channel. The model provides a useful tool for environmental planning, protection and proposed wetland restoration works.

Conservation of Natural Resources↗

Evidence for direct protein kinase-C mediated modulation of N-methyl-D-aspartate receptor current.

Protein kinase-C (PKC) activation differentially affects currents from N-methyl-D-aspartate (NMDA) type glutamate receptors depending upon their subunit composition. Experiments using chimeras initially indicated that the cytoplasmic C-terminal tails of NR2B (responsive to PKC) and NR2C (unresponsive to PKC) subunits contain the amino acid residues responsible for the observed disparity of PKC effects. However, truncation and point mutation experiments have suggested that PKC action on NMDA receptors may be entirely indirect, working via the phosphorylation of associated proteins. Here we suggest that PKC does, in fact, affect NR2B/NR1-011 NMDA currents by direct phosphorylation of the NR2B tail at residues S1303 and S1323. Replacement of either of these residues with Ala severely reduces PKC potentiation. To verify that S1303 and S1323 are sites of direct phosphorylation by PKC, synthetic peptides from the regions surrounding these sites were used as substrates for in vitro assays with purified rat brain PKC. These results indicate that PKC can directly phosphorylate S1303 and S1323 in the NR2B C terminus, leading to enhanced currents through NMDA receptor channels. The direct action of PKC on certain NMDA receptor subtypes may be important in any physiological or pathological process where PKC and NR2B/NR1 receptors interact.

Animals↗

Off-host observations of mating and postmating behaviors in the cat flea (Siphonaptera: Pulicidae).

A blood meal was necessary for a male cat flea, Ctenocephalides felis (Bouché), to display the mating attempts to an unfed or fed female. More mating pairs resulted when both sexes were fed. Copulation occurred when fed fleas were placed on surfaces with temperatures from 34 to 42 degrees C. This article not only describes the mating and postmating behaviors of cat fleas, but also compares them with those of other fleas. The sequence of mating behavior began when a male approached a female ventrally, and the male's antennae and claspers became erect to attach to the abdomen of the female. Clasper attachment lasted until copulation ended, whereas the male retrieved his antennae immediately after genitalia linkage. The male generally grasped the female's tarsi with his claws during mating. The length of the mating interval terminated by the male ranged from 25 to 110 min and was significantly longer than that terminated by the female (averaging 12.11 min). After the mating pair separated, the male displayed a series of postmating behaviors discussed herein. This article documents grasping and postmating behaviors of the male cat flea.

Animals↗

Autocrine regulation of interleukin-8 production in human monocytes.

Interleukin (IL)-8 is a C-X-C chemokine that plays an important role in acute inflammation through its G protein-coupled receptors CXCR1 and CXCR2. In this study, we investigated the role of IL-8 as an autocrine regulator of IL-8 production and the signaling mechanisms involved in human peripheral blood mononuclear cells (MNCs). Sepharose-immobilized IL-8 stimulated a sevenfold increase in IL-8 production within 2 h. IL-8 induced the expression of its own message, and IL-8 biosynthesis was inhibited by cycloheximide and actinomycin D, indicating de novo RNA and protein synthesis. In contrast to MNCs, polymorphonuclear neutrophils did not respond to the immobilized IL-8 with IL-8 production despite cell surface expression of CXCR1 and CXCR2. Melanoma growth-stimulatory activity/growth-related protein-alpha (MGSA/GROalpha), which binds CXCR2 but not CXCR1, was unable to either stimulate IL-8 secretion in MNCs or desensitize these cells to respond to immobilized IL-8. The involvement of mitogen-activated protein kinase (MAPK) in IL-8-induced IL-8 biosynthesis was suggested by the ability of PD-98059, an inhibitor of MAPK kinase, to block this function. Furthermore, IL-8 induced a significant increase in extracellular signal-regulated kinase 2 phosphorylation, whereas MGSA/GROalpha was much less effective. These findings support the role of IL-8 as an autocrine regulator of IL-8 production and suggest that this function is mediated by CXCR1 through activation of MAPK.

Antibodies, Monoclonal↗

Effects of multiple mating on female reproductive output in the cat flea (Siphonaptera: Pulicidae).

Multiple mating behavior of female cat fleas, Ctenocephalides felis (Bouché), was confirmed in this study, and its effects on fecundity and fertility were investigated as well. The number of fertile eggs produced by mated females was close to nil within 7 d after removal of males, but it was resumed when females were exposed to males again on day 7. Multiple-mated females displayed significantly higher fecundity (400.3 eggs per female) and fertility (182.8 viable eggs per female) than single-mated females (61.7 and 19.0, respectively) in the 24-d period, suggesting that multiple mating by females is an advantageous strategy for cat fleas. The duration of first mating averaged 63.1 min. The high ratio (55.56%) and short duration (34.0 min) of impotent mating suggested that cryptic female choice may be involved during copulation.

Animals↗

NF-kappaB activation is required for C5a-induced interleukin-8 gene expression in mononuclear cells.

C5a, a potent peptide chemoattractant, stimulates interleukin-8 (IL-8) secretion from peripheral blood mononuclear cells (PBMC). Experiments were conducted to understand the mechanisms for C5a-induced IL-8 production, which was 14-fold greater than that in unstimulated cells by 2 hours. IL-8 secretion was accompanied by accumulation of IL-8 mRNA in the cytosol and by nuclear expression of a kappaB DNA binding activity within 30 minutes. AP-1 but not NF-IL-6 DNA binding activity was also detected in C5a-stimulated PBMC; however, its delayed expression (maximal at 4 hours) suggested a less important role in the rapid production of IL-8. The correlation between C5a-induced kappaB binding activity and IL-8 gene expression was examined in the RAW264.7 macrophage cells using reporter genes directed by the kappaB sequence from IkappaBalpha and IL-8 promoter regions. C5a-induced reporter gene expression was abolished by introducing mutations into the kappaB sites and by coexpression of a dominant negative IkappaBalpha construct resistant to agonist-induced phosphorylation. Pertussis toxin, which ADP-ribosylates the Gi proteins known to couple to the C5a receptor, produced minimal inhibition of C5a-induced IL-8 expression and had little effect on C5a-induced calcium mobilization in RAW264.7 cells. These results suggest that NF-kappaB activation is required for C5a-induced IL-8 gene expression and that this response is mediated primarily through a pertussis toxin-insensitive pathway.

Animals↗

A carboxyl-terminal extension of the zinc finger domain contributes to the specificity and polarity of peroxisome proliferator-activated receptor DNA binding.

Heterodimers of the peroxisome proliferator-activated receptors (PPAR) and the retinoid X receptors (RXR) recognize response elements (PPREs) that exhibit the consensus sequence 5'-A(A/T)CT(A/G)GGNCAAAG(G/T)TCA-3'. The consensus PPRE includes both a 5'-extension and a direct repeat (DR1) comprised of two canonical core recognition sequences (underlined) for nuclear receptor zinc fingers separated by a single nucleotide spacer. The extended binding site recognized by PPARs is very similar to sites that bind monomers of the nuclear receptors Rev-ErbA and ROR suggesting that the latter could bind to PPREs and affect gene transcription. However, Rev-ErbA and ROR bind weakly to naturally occurring PPREs relative to the consensus binding site, and significant effects on PPARalpha transactivation of a CYP4A6-Z reporter were not observed. In contrast, PPAR/RXR heterodimers bind to a DR2 element containing the conserved 5'-extended sequence that is recognized by dimers of RORalpha or Rev-ErbA. PPARalpha/RXRalpha positively regulate transcription from this element, and co-expression of Rev-ErbA blocks this effect. The nuclear receptors NGFI-B and ROR utilize a carboxyl-terminal extension (CTE) of the zinc finger DNA binding domain in their interactions with the 5'-extension of a single zinc finger-binding site. DNA binding domains (DBD) of PPARs alpha, delta, and gamma that contain the zinc finger motif and a CTE display binding to core recognition sequences that is dependent on the 5'-extended sequence found in PPREs. Unlike DBDs of other nuclear receptors that form heterodimers with RXR, the PPAR-DBDs did not exhibit cooperative binding with the DBD of RXR and exhibit the opposite polarity for binding to the direct repeat motif. In contrast to the corresponding DBD of RXR, the PPAR-DBDs bind as monomers to a single extended binding site as well as to the consensus PPRE. A chimera linking the zinc finger domain of RXRalpha to the CTE from PPARalpha bound to a single extended binding site indicating a functional role for the CTE of PPARs in extended binding site recognition.

Amino Acid Sequence↗

Identification of thyroid hormone response elements in the human fatty acid synthase promoter.

To investigate the regulation of the human fatty acid synthase gene by the thyroid hormone triiodothyronine, various constructs of the human fatty acid synthase promoter and the luciferase reporter gene were transfected in combination with plasmids expressing the thyroid hormone and the retinoid X receptors in HepG2 cells. The reporter gene was activated 25-fold by the thyroid hormone in the presence of the thyroid hormone receptor. When both the thyroid hormone and the retinoid X receptors were expressed in HepG2 cells, there was about a 100-fold increase in reporter gene expression. 5'-Deletion analysis disclosed two thyroid hormone response elements, TRE1 (nucleotides -870 to -650) and TRE2 (nucleotides -272 to -40), in the human fatty acid synthase promoter. The presence of thyroid hormone response elements in these two regions of the promoter was confirmed by cloning various fragments of these two regions in the minimal thymidine kinase promoter-luciferase reporter gene plasmid construct and determining reporter gene expression. The results of this cloning procedure and those of electrophoretic mobility shift assays indicated that the sequence GGGTTAcgtcCGGTCA (nucleotides -716 to -731) represents TRE1 and that the sequence GGGTCC (nucleotides -117 to -112) represents TRE2. The sequence of TRE1 is very similar to the consensus sequence of the thyroid hormone response element, whereas the sequence of TRE2 contains only a half-site of the thyroid hormone response element consensus motif because it lacks the direct repeat. The sequences on either side of TRE2 seem to influence its response to the thyroid hormone and retinoid X receptors.

Base Sequence↗

Peroxisome proliferator activated receptor-alpha expression in human liver.

The peroxisome proliferator activated receptor alpha (PPAR) is a member of the steroid/hormone receptor superfamily that mediates the peroxisome proliferator-dependent transcriptional activation of genes encoding several peroxisomal and microsomal enzymes as well as peroxisome proliferation. Human liver is refractory to the pathological effects of peroxisome proliferators that are seen in mice. With the use of RNase protection assays, the ratio of hepatic PPAR alpha mRNA to beta-actin mRNA was found to be 1 order of magnitude lower in humans than that observed in mice. In addition, the isolation of human cDNA for PPAR alpha that does not encode a functional PPAR because it lacks exon 6 as a result of alternate RNA splicing suggested that this process might also diminish the expression of PPAR alpha. RNase protection analysis of total RNA revealed the presence of splice variants lacking exon 6 at significant levels in all 10 human liver samples examined. Supershift analysis using the CYP4A6-Z peroxisome proliferator response element and antisera specific for PPAR alpha revealed easily detectable amounts of PPAR alpha DNA binding activity in mouse liver lysates, whereas human liver lysates contained > 10-fold lower amounts of PPAR alpha DNA binding activity. In contrast to mouse lysates, the amount of PPAR alpha binding in human lysates was generally less than that of other unidentified proteins. These results suggest that although humans retain the coding potential for a functional receptor, the low levels of PPAR alpha expression in liver may be insufficient to compete effectively with other proteins that bind to peroxisome proliferator response elements.

Alternative Splicing↗

Phosphorylation of the N-formyl peptide receptor is required for receptor internalization but not chemotaxis.

The human N-formyl peptide receptor (FPR) is a member of the family of leukocyte, G protein-coupled, chemoattractant receptors. To determine the role(s) of receptor phosphorylation in FPR processing and formylmethionylleucylphenylalanine (fMLF)-mediated chemotaxis, we utilized U937 cells expressing the recombinant wild type receptor and a mutant form of the FPR. This mutant, which lacks all of the serine and threonine residues in the C terminus of the receptor, DeltaST, has recently been shown to produce a receptor capable of fMLF binding and G protein activation but was demonstrated not to undergo fMLF-dependent phosphorylation or desensitization of the calcium mobilization response upon repeated exposure to agonist (Prossnitz, E. R. (1997) J. Biol. Chem. 272, 15213-15219). In this report, we examined the role of receptor phosphorylation in FPR internalization and leukocyte chemotaxis. Whereas the wild type receptor was rapidly internalized upon stimulation, the phosphorylation-deficient mutant was not, remaining entirely on the cell surface. In addition, contrary to the hypothesis that receptor processing and recycling are required for chemotaxis, we found no defect in the ability of the mutant FPR to migrate up a concentration gradient of fMLF. These results indicate that phosphorylation of the FPR is a necessary step in receptor internalization but that receptor phosphorylation, desensitization, and internalization are not required for chemotaxis.

Calcium↗

Salvage neck dissection for cervical recurrence of nasopharyngeal carcinoma.

OBJECTIVE: To evaluate the effectiveness of salvage neck dissection as part of a multidisciplinary treatment approach in persistent or recurrent metastatic nasopharyngeal carcinoma, after failure of initial radiotherapy at the regional site. DESIGN: A retrospective study of 31 patients treated during a 14-year period from March 1981 through May 1995, with a maximum follow-up of 152 months. Factors evaluated include patients' sex, age, and initial stage of tumor, mobility and number of nodal recurrences, surgical and pathological findings, and postoperative irradiation. SETTING: Academic tertiary referral center. PATIENTS: Twenty-six men and 5 women were studied; one patient had neck dissection to both sides of the neck on separate occasions, for a total of 32 operations. All patients had pathologically proved nasopharyngeal carcinoma and had been previously treated at the primary site and both sides of the neck with definitive radiotherapy. INTERVENTION: Patients underwent a radical, modified radical, or level I-sparing radical neck dissection. MAIN OUTCOME MEASURE: Surgical morbidity, time to recurrence at the regional site, and survival time. RESULTS: Clinically, there was a disease predilection of 81% at levels II and V. Surgical morbidity was minimal. Regional control was achieved in 20 (65%) of the patients, and the overall 5-year survival was 67%. Tumor involvement of the posterior triangle musculature and spinal accessory nerve was associated with failure to control neck disease. Extracapsular nodal extension correlated with a poor survival outcome. CONCLUSION: Control of regional disease by salvage neck dissection when radiotherapy has failed is both safe and effective in properly selected patients.

Adult↗

Cloning and functional characterization of the mouse C3a anaphylatoxin receptor gene.

The mouse anaphylatoxin C3a receptor (mC3aR) gene was isolated using a human C3aR cDNA probe. The genomic fragment contains an open reading frame of 1431 base pairs that encodes a peptide of 477 amino acids. A cDNA with identical sequence was subsequently obtained from the mouse pre-B cell line 70Z/3 by reverse transcriptase polymerase chain reaction based on sequence of the mC3aR gene. Northern blot analysis suggested expression of the mC3aR in lung and heart, and to a lesser extent, in brain, liver, muscle, kidney, and testis. The deduced amino acid sequence of the mouse C3aR is 65% identical to that of the human C3aR. Like the human receptor, mouse C3aR contains a predicted large extracellular loop of approximately 165 amino acids (residues 161-325) between the fourth and fifth transmembrane domains. This loop, however, is the least conserved structure (45% identical sequence) of all the extracellular and intracellular domains between the mouse and human C3aRs. The mouse gene product bound 125I-labeled human C3a with a Kd of 2.54 nM when expressed in the stably transfected rat basophilic leukemic cell line RBL-2H3. Bound C3a could be effectively displaced by excess quantities of unlabeled C3a, but not by C4a or C5a. C3a induced dose-dependent calcium mobilization in the transfected cells, which could be blocked by pertussis toxin treatment. These results confirm that the cloned gene encodes a functional C3aR capable of coupling to a pertussis toxin-sensitive G protein. The sequence divergence of the large extracellular loop does not appear to affect C3a binding and transmembrane signaling.

Amino Acid Sequence↗