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Biomedical subjects

W Hsu

Publications and source records attributed to W Hsu.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effect of shock timing on defibrillation success.

The goal of this study was to determine whether delivering transvenous defibrillation shocks, coordinated with the up/down-slope VF waveform patterns in the shocking lead, would improve the probability of successful defibrillation. Anesthetized swine (32-38 kg, n = 8) were implanted with an RV-->SVC + SQArray transvenous system to measure VF waveform patterns and to deliver shocks. The shocks were generated by a Cardiac Pacemakers Inc. biphasic waveform generator. Energy required for 50% success probability (E50) was determined using the multishock up-down protocol. VF was repeatedly induced and defibrillation shocks at E50 were given after 10 seconds. The defibrillation outcome, delivered energy (Ed), peak voltage (V), peak current (I), system impedance (Z) and VF waveform pattern at the time of shock were recorded and measured. Out of a total of 685 shocks, 324 (47%) succeeded and 361 (53%) failed. The Ed, V, I, and Z were similar for the two defibrillation outcome groups (success or failure). VF patterns were classified as high or low amplitude at the time of the shock based on the peak-to-peak amplitude of signals recorded between the shocking electrodes. Shocks that coincided with high amplitude VF patterns were further divided into shocks that occurred on the up-slope or on the down-slope. The probability of success when the E50 shocks were coincident with high or low amplitude fibrillation did not differ significantly (Student's t-test: 46% vs 48%. P = NS). However, during high amplitude fibrillation, shocks delivered on the up-slope were significantly more successful than those delivered on the down-slope (Chi-square: 67% vs 39%; P < 0.001). These results suggest that delivering defibrillation shocks during the up-slope of the high amplitude signal in the shocking lead may improve the probability of successful defibrillation of ICDs.

Animals↗
PubMed1997

Purification of the infectious bovine rhinotracheitis virus alkaline deoxyribonuclease expressed in Escherichia coli.

Nucleotide sequence analysis within the unique long segment of the infectious bovine rhinotracheitis virus (IBRV) genome identified an open reading frame of 1461 base pairs whose deduced polypeptide of 487 amino acids exhibited homology to alkaline deoxyribonucleases of other herpesviruses. To determine whether this IBRV gene product has nuclease activity, the gene designated UL12 was inserted into the vector pET-28a(+) and expressed in Escherichia coli as an oligohistidine-tagged protein. Upon induction with isopropyl beta-D-thiogalactopyranoside E. coli BL21 (DE3)[pLysS] cells harboring this recombinant plasmid produced a 57-kDa protein, the molecular mass of which was in accordance with the prediction from the nucleotide sequence. A one-step purification procedure using metal affinity chromatography resulted in a homogeneous preparation of this recombinant protein. The purified protein exhibited both exonuclease and endonuclease activities, each with an alkaline pH optimum.

Animals↗
PubMed1996

Functional expression of the bovine herpesvirus 1 alkaline deoxyribonuclease (UL12) in Escherichia coli.

Sequence analysis within the unique long segment of the bovine herpesvirus 1 (BHV-1; infectious bovine rhinotracheitis virus) genome identified an open reading frame whose deduced protein product of 487 amino acids exhibited homology to alkaline deoxyribonucleases (DNases) of other herpesviruses. To determine this BHV-1 gene product has nuclease activity, the gene designated UL12 was inserted into the vector pET-28a(+) and expressed in Escherichia coli as an oligohistidine-tagged protein. Upon induction with isopropyl beta-D-thiogalactopyranoside E. coli BL21 (DE3) [pLysS] cells carrying this recombinant plasmid produced a 57-kDa protein, the molecular mass of which was in accordance with the prediction from the DNA sequence. The recombinant UL12 protein purified by nickel-chelating affinity chromatography exhibited both exonuclease and endonuclease activity, each with an alkaline pH optimum.

Chromatography, Affinity↗
PubMed1996

The UL2 open reading frame of bovine herpesvirus 1 encodes a uracil-DNA glycosylase.

Sequence analysis within the unique long segment of the bovine herpesvirus 1 (BHV-1) genome previously identified an open reading frame (ORF), designated UL2, whose deduced polypeptide of 204 amino acids contained a consensus uracil-DNA glycosylase (UDGase) signature sequence. To determine whether the BHV-1 UL2 ORF product has UDGase activity, we positioned the UL2 sequence down-stream of the T7 promoter on the vector pET-28b(+) and expressed it in Escherichia coli. Upon induction with isopropyl beta-D-thiogalactopyranoside these cells produced a 23-kDa protein, the molecular mass of which was in accordance with the prediction from the nucleotide sequence. A one-step purification procedure using nickel-chelating affinity chromatography resulted in a homogeneous preparation of this protein, which displayed specific UDGase activity in an in vitro enzyme assay. These results provide evidence that the BHV-1 UL2 gene does encode a UDGase.

Amino Acid Sequence↗
PubMed1996

Intestinal absorption studies on peptide mimetic alpha-methyldopa prodrugs.

Two dipeptide mimetic prodrugs, 1 and 2, and two tripeptide mimetic prodrugs, 3 and 4, of L-alpha-methyldopa were evaluated for intestinal absorption by in-situ single pass rat jejunal perfusion studies and by in-vitro uptake experiments in brush-border membrane vesicles (BBMVs) prepared from rat intestine. In the perfusion studies, compound 1 demonstrated a 3.5-fold increase in permeability (Pm* = 2.27) as compared with that of alpha-methyldopa (Pm* = 0.65), indicating that this prodrug was better absorbed in the intestine than its parent drug. Other prodrugs showed no significant improvement in intestinal permeability. The results correlated with the results of BBMV uptake studies. In the presence of an inward proton gradient, compound 1 showed Michaelis-Menton saturable kinetics of BBMV uptake with a low value of K(m) (0.06 +/- 0.13 mM) and a high value of Vmax/K(m)(36.38 nmol (mg protein)-1/30s mM-1) at a low concentration range and a linear uptake at high concentrations with Kd = 0.14 +/- 0.02 mM. Compounds 2 and 3 were mainly taken up in BBMVs via passive diffusion. Compound 4 was taken up in BBMVs basically via the carrier-mediated transport system, while the rate of uptake was much lower than that of compound 1. The uptake of compounds 1 and 4 was significantly inhibited by dipeptides L-Gly-L-Pro and L-Gly-L-Phe, and cephradine, a beta-lactam known to be transported via the dipeptide carrier system, indicating that both compounds were taken up in BBMVs via the H(+)-coupled dipeptide-mediated transport system. In contrast to the complicated uptake profile of alpha-methyldopa, the higher rate of BBMV uptake with less variation demonstrated on compound 1 suggested that the attached nonessential amino acid moiety, D-phenylglycine, is a feasible delivery tool in carrying the parent drug through the intestine.

Animals↗
PubMed1995

A perspex flattening filter for a 300k Vp orthovoltage X-ray beam.

For economic reasons modern equipment which produces low to medium energy X-rays covers the whole range of beam qualities from traditional superficial to orthovoltage radiation qualities. A recent trend shows an increasing number of installations of orthovoltage units in the cancer therapy community in the last five years. The use of a single anode for accelerating voltages between 60 and 300 kVp leads to compromises with regards to beam flatness and symmetry in the anode/cathode direction of the Siemens Stabilipan II radiation beam. A perspex flattening filter was designed to improve these beam parameters of the 300 kVp radiation beam (HVT 4mm Cu) at 50 cm and 60 cm FSD using a diaphragm-mounted field defining device. The filter design correlates with focal spot characteristics of the beam. The use of the filter improves flatness and symmetry for all measured field sizes from 6 x 6 cm2 to 18 x 18 cm2 by up to 8% (flatness) and 7% (symmetry) respectively. No significant difference in the depth dose characteristic of the 300 kVp beam was found with and without the filter. The only modification in the planning procedures required is the use of an attenuation factor of 0.89 for the filter. The use of the filter improves the dose distribution in treatment of patients undergoing orthovoltage radiotherapy--in particular treatments with large field sizes such as for metastases in the spinal column.

Radiographic Image Enhancement↗
PubMed1994

Fos and Jun repress transcription activation by NF-IL6 through association at the basic zipper region.

NF-IL6 and AP-1 family transcription factors are coordinately induced by interleukin-6 (IL-6) in a cell-type-specific manner, suggesting that they mediate IL-6 signals in the nucleus. We show that the basic leucine zipper (bZIP) region of NF-IL6 mediates a direct association with the bZIP regions of Fos and Jun in vitro. This interaction does not depend on the presence of their cognate recognition DNA elements or the posttranslational modification of either partner. NF-IL6 homodimers can bind to both NF-IL6 and AP-1 sites, whereas Fos and Jun cannot bind to most NF-IL6 sites. Cross-family association with Fos or with Jun alters the DNA binding specificity of NF-IL6 and reduced its binding to NF-IL6 sites. NF-IL6 isoforms that differ in the site of translation initiation have distinct transcriptional activities. Activation of a reporter gene linked to the NF-IL6 site by NF-IL6 is repressed by Fos and by Jun in transient transfection assays. Thus, association with AP-1 results in repression of transcription activation by NF-IL6. The repression is NF-IL6 site dependent and may have a role in determining the promoter and cell type specificity in IL-6 signaling.

Base Sequence↗
PubMed1994

NF-IL6 and AP-1 cooperatively modulate the activation of the TSG-6 gene by tumor necrosis factor alpha and interleukin-1.

Tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) activate transcription of the TSG-6 gene in normal human fibroblasts through a promoter region (-165 to -58) that encompasses an AP-1 and a NF-IL6 site. We show by deletion analysis and substitution mutagenesis that both sites are necessary for activation by TNF-alpha. Activation by IL-1 requires the NF-IL6 site and is enhanced by the AP-1 site. These results suggest that the NF-IL6 and AP-1 family transcription factors functionally cooperate to mediate TNF-alpha and IL-1 signals. Consistent with this possibility, IL-1 and TNF-alpha markedly increase the binding of Fos and Jun to the AP-1 site, and NF-IL6 activates the native TSG-6 promoter. Activation by NF-IL6 requires an intact NF-IL6 site and is modulated by the ratio of activator to inhibitor NF-IL6 isoforms that are translated from different in-frame AUGs. However, the inhibitor isoform can also bind to the AP-1 site and repress AP-1 site-mediated transcription. The finding that the inhibitor isoform antagonizes activation of the native TSG-6 promoter by IL-1 and TNF-alpha suggests that NF-IL6 has a physiologic role in these cytokine responses. Thus, the functionally distinct NF-IL6 isoforms cooperate with Fos and Jun to positively and negatively regulate the native TSG-6 promoter by TNF-alpha and IL-1.

Base Sequence↗
PubMed1993

Nuclear signaling by interleukin-6.

The molecular analysis of the regulation of nuclear proteins induced by interleukin-6 has provided new insights into this largely unknown signal transduction pathway. Transcription factors of the CCAAT/enhancer-binding protein and AP-1 families, as well as the octamer-binding proteins and the tumor suppressor gene product pRB, are regulated by interleukin-6 in a cell type specific manner, suggesting that they may play a role in the nuclear signaling by interleukin-6.

Animals↗
PubMed1993

Low dose rate teletherapy and tumour response.

Tumour responses in 25 patients with locally advanced head and neck cancer, treated on an experimental fractionated low dose rate (FLDR) teletherapy program are reported. Treatment was given at dose rates ranging from 1.8 to 3 Gy/h to a range of total doses from 32-38 Gy, with palliative intent. The total doses delivered have been predicted by the linear quadratic formula to be equivalent to 33-41 Gy using conventionally fractionated high dose rate treatment, in terms of acute normal tissue effects. A complete response rate (no visible or palpable disease 2 months after treatment) was observed in 28% of cases. Analysis of these response rates suggests that the linear quadratic formula may underestimate the anti-tumour effect of FLDR teletherapy at the various dose rates and total dose permutations in this study.

Carcinoma, Squamous Cell↗
PubMed1993

Convergent regulation of NF-IL6 and Oct-1 synthesis by interleukin-6 and retinoic acid signaling in embryonal carcinoma cells.

The nuclear signaling by the pleiotropic cytokine interleukin-6 (IL-6) has been investigated in human embryonal carcinoma cells and T cells. We show that Oct-1, a ubiquitously expressed octamer-binding protein known to be regulated posttranslationally, can also be regulated at the levels of mRNA and protein synthesis by IL-6 and by retinoic acid (RA) in human embryonal carcinoma cells. NF-IL6, an IL-6-inducible transcription factor of the C/EBP family, can confer this regulation and is itself regulated by both signals. The abundance and the molar ratios of the three forms of NF-IL6, corresponding to peptides initiated in frame from different AUGs of the same NF-IL6 mRNA species, are regulated by IL-6 and by RA. These results suggest that the two signal transduction pathways overlap in human embryonal carcinoma cells and that Oct-1 may be downstream of NF-IL6 in the shared regulatory cascade. Enhanced Oct-1 synthesis correlates with one of the functions of Oct-1, i.e., stimulation of adenovirus DNA replication. This provides an example of a possible functional consequence of IL-6 and RA signaling that is mediated by NF-IL6 and Oct-1 regulation.

Adenoviruses, Human↗
PubMed1993

The ClusNet algorithm and time series prediction.

This paper describes a novel neural network architecture named ClusNet. This network is designed to study the trade-offs between the simplicity of instance-based methods and the accuracy of the more computational intensive learning methods. The features that make this network different from existing learning algorithms are outlined. A simple proof of convergence of the ClusNet algorithm is given. Experimental results showing the convergence of the algorithm on a specific problem is also presented. In this paper, ClusNet is applied to predict the temporal continuation of the Mackey-Glass chaotic time series. A comparison between the results obtained with ClusNet and other neural network algorithms is made. For example, ClusNet requires one-tenth the computing resources of the instance-based local linear method for this application while achieving comparable accuracy in this task. The sensitivity of ClusNet prediction accuracies on specific clustering algorithms is examined for an application. The simplicity and fast convergence of ClusNet makes it ideal as a rapid prototyping tool for applications where on-line learning is required.

Algorithms↗
PubMed1992

NF-IL6, a member of the C/EBP family, regulates E1A-responsive promoters in the absence of E1A.

A cDNA encoding NF-IL6, an interleukin-6 (IL-6)-regulated human nuclear factor of the C/EBP family, is demonstrated to complement the transactivation function of E1A. The endogenous NF-IL6 level varies according to cell type and correlates positively with an IL-6-regulated cellular E1A-substituting activity that was described recently (J.M. Spergel and S. Chen-Kiang, Proc. Natl. Acad. Sci. USA 88:6472-6476, 1991). When expressed by transfection in cells which contain low levels of NF-IL6 and are incapable of complementing the function of E1A proteins, NF-IL6 also transactivates the E1A-responsive E2ae and E1B promoters, to the same magnitude as E1A. Activation by NF-IL6 is concentration dependent and sequence specific: mutational studies of the E2ae promoter suggest that the promoter-proximal NF-IL6 recognition site functions as a dominant negative regulatory site whereas the promoter-distal NF-IL6 recognition site is positively regulated at low NF-IL6 concentrations and negatively regulated when the NF-IL6 level is high. Consistent with these functions, NF-IL6 alone is sufficient to complement an E1A deletion mutant dl312 in viral infection, when expressed at appropriate concentrations. These results identify NF-IL6 as a sequence-specific cellular nuclear factor which regulates E1A-responsive genes in the absence of E1A.

Adenovirus Early Proteins↗
PubMed1991

Hearing loss and pneumococcal meningitis: an animal model.

Clinical studies of predisposing factors in the development of hearing loss secondary to bacterial meningitis have produced conflicting results. An animal model of meningogenic labyrinthitis was developed for more precise study of these parameters. Rabbits were inoculated intrathecally with 10(5) pneumococci to induce meningitis. Hearing thresholds were measured using auditory-evoked responses to 1 kHz, 10 kHz, and click stimuli before infection and every 12 hours thereafter. Profound deafness occurred in all subjects at an average of 48 hours following infection. The incidence and severity of hearing loss was strongly correlated with the duration of meningitis. Temporal bone histology revealed acute inflammation of all perilymphatic spaces including the cochlear aqueduct. This model demonstrated that the risk and severity of hearing loss increase with the duration of meningitis and suggested that the cochlear aqueduct is an anatomic pathway for the extension of infection from the cerebrospinal fluid to the cochlea. The implications for therapy in humans is discussed.

Acoustic Stimulation↗
PubMed1991

Neuroendocrine differentiation and prognosis of extrahepatic biliary tract carcinomas.

From 1980 to 1987, 35 patients underwent exploratory surgery for carcinomas of the extrahepatic biliary tract (EBT). Samples from 28 of these tumors (15 gallbladder, 13 bile duct) were assessed by immunohistochemical analysis for exocrine and/or neuroendocrine differentiation. Seven patients were excluded from the study because of insufficient available specimen or loss to follow-up. Paraffin sections were immunostained for neuroendocrine differentiation markers: neuron-specific enolase (NSE), chromogranin-A, synaptophysin, serotonin, somatostatin, substance-P, and glucagon. Additional sections were also stained with monoclonal antibody A-80 that recognizes a glycoprotein related to exocrine differentiation. The tumors were reclassified on the basis of immunophenotyping data: (I) pure exocrine carcinoma (n = 8); (II) predominantly exocrine carcinoma with occasional neuroendocrine cells (n = 9); (III) mixed exocrine-neuroendocrine carcinoma (n = 4); (IV) pure neuroendocrine (n = 2); and (V) predominantly neuroendocrine with occasional exocrine cells (n = 5). Survival time among the two pure neuroendocrine (group IV) and five predominantly neuroendocrine carcinomas (group V) was significantly less than the survival time of patients from the other groups (2.6 +/- 2.2 months vs 13.5 +/- 12.3 months; p = 0.015). No difference was noted between groups in extent of disease, treatment rendered, or location of tumor (bile duct vs gallbladder). This study indicates that (1) the incidence of neuroendocrine differentiation in cancers of the EBT is higher than generally recognized, (2) carcinomas of the EBT may be phenotypically reclassified on the basis of immunohistochemical analysis, and (3) the presence of pure or predominant neuroendocrine differentiation in carcinomas of the EBT is associated with shorter survival time than carcinomas with pure or predominant exocrine differentiation (or mixed exocrine and neuroendocrine factors).

Biliary Tract Neoplasms↗