Biomedical subjects

J Hwang

Publications and source records attributed to J Hwang.

At least 19 recordsLinked to original sources

PubMed2006

Magnetic resonance spectroscopy for measuring the biodistribution and in situ in vivo pharmacokinetics of fluorinated compounds: validation using an investigation of liver and heart disposition of tecastemizole.

BACKGROUND AND OBJECTIVE: The study of biodistribution and in situ pharmacokinetics is a challenging, but sometimes very important, aspect of premarketing characterization of drugs. We aimed to develop a non-invasive fluorine magnetic resonance (MR) spectroscopic method for the absolute quantitation of a mono-fluorinated compound and of its metabolites in the heart and liver of healthy subjects for this purpose. METHOD: We used fluorine MR spectroscopy (MRS) at 4 T (Tesla) and external standardization in an open label multiple-dose study. Twenty-three healthy adult subjects were enrolled in the study. The surface coil localized fluorine MR spectrum was monitored in the heart and liver at baseline and after oral administration of multiple doses of tecastemizole. Steady-state measurements were made at set time points that depended upon dose, and washout measurements were made only on subjects in which in vivo fluorine signal was observed. RESULTS AND DISCUSSION: At 4 T, under the given experimental conditions, the method had a lower limit of quantitation (LLOQ) of about 2.6 microm and a limit of detection (LOD) of about 0.3 microm for solution state samples (linewidth approximately 15 Hz). The measurement reproducibility was 6.4% using a 50 microm phantom. The effect of MR operator and spectral analyst on the calculated calibration curve slope was small, with inter-rater correlation coefficients of 0.999 and 0.998 respectively. MR signal from fluorine-containing tecastemizole-related moieties was observed in situ only at day 8 in the liver of three of five subjects dosed at 270 mg/day. The average in situ concentration was estimated to be 58+/-22 microm, with an average test-retest reproducibility of 216%. Extrapolating the in vitro results to human measurements, with an approximate linewidth of 250 Hz, predicts in situ LOD and LLOQ values of approximately 6 and 44 microm respectively. However, the human study had a fluorine MRS LOD of approximately 20 microm. The decrease in sensitivity and the increase in variability of the in vivo, in situ measurements compared with the validation study most likely arose from coil placement and incomplete rephasing of the MR signal by the respiratory phase compensation method. CONCLUSION: The measured concentrations were the lowest ever recorded for a multi-dose exogenous mono-fluorinated compound in the human liver using a validated fluorine MR quantitation method. The proposed non-invasive MR method for studying the biodistribution and in situ pharmacokinetics of mono-fluorinated compounds in the liver and heart should have broader application to the development of non-invasive biomarkers.

Adult↗

PubMed2005

Serum CA19-9 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer.

The use of serial serum measurements of the carbohydrate antigen 19-9 (CA19-9) to guide treatment decisions and serve as a surrogate end point in clinical trial design requires further validation. We investigated whether CA19-9 decline represents an accurate surrogate for survival and time to treatment failure (TTF) in a cohort of 76 patients with advanced pancreatic cancer receiving fixed-dose rate gemcitabine in three separate studies. Statistically significant correlations between percentage CA19-9 decline and both overall survival and TTF were found, with median survival ranging from 12.0 months for patients with the greatest degree of biomarker decline (> 75%) compared with 4.3 months in those whose CA19-9 did not decline during therapy (P < 0.001). Using specific thresholds, patients with > or = 25% decline in CA19-9 during treatment had significantly better outcomes than those who did not (median survival and TTF of 9.6 and 4.6 months vs 4.4 and 1.5 months; P < 0.001). Similar results were seen using both 50 and 75% as cutoff points. We conclude that serial CA19-9 measurements correlate well with clinical outcomes in this patient population, and that decline in this biomarker should be entertained for possible use as a surrogate end point in clinical trials for the selection of new treatments in this disease.

Antimetabolites, Antineoplastic↗

PubMed2005

Optical phonon sidebands of electronic intersubband absorption in strongly polar semiconductor heterostructures.

We present the first evidence for a distinct optical phonon progression in the linear and nonlinear intersubband absorption spectra of electrons in a GaN/Al(0.8)Ga(0.2)N heterostructure. Femtosecond two-color pump-probe experiments in the midinfrared reveal spectral holes on different vibronic transitions separated by the LO-phonon frequency. These features wash out with a decay time of 80 fs due to spectral diffusion. The remaining nonlinear transmission changes decay with a time constant of 380 fs. All results observed are described by the independent boson model.

Journal Article↗

PubMed2005

Effects of epidural naloxone on pruritus induced by epidural morphine: a randomized controlled trial.

BACKGROUND: Epidural morphine produces prolonged analgesia but has many side effects including pruritus. Naloxone is an antagonist that can reverse the side effects of morphine. METHOD: We studied the effects of continuously administered epidural naloxone mixed with morphine on side effects and analgesia in a randomized, double blind, two-armed study. Fifty-eight pregnant women undergoing cesarean section were enrolled. All patients received a 4-mg epidural bolus of morphine in the post-anesthetic care unit. After this, patients in group M (n=28) received continuous epidural morphine (6 mg over 48 h) in 0.1% bupivacaine; patients in group N (n=30) received an epidural infusion containing naloxone (1.2 mg over 48 h) and morphine (6 mg over 48 h) in 0.1% bupivacaine. The infusion rate was 2 mL/h. RESULTS: The incidence (82% versus 47%) and severity of pruritus were lower in group N than group M (P=0.001). There were no significant differences in pain score or in the incidence of nausea, vomiting or urinary disturbance between groups. CONCLUSION: Continuous epidural infusion of naloxone combined with morphine is effective in reducing the incidence and severity of pruritus induced by epidural morphine.

Adult↗

PubMed2005

Combustion characteristics of paper mill sludge in a lab-scale combustor with internally cycloned circulating fluidized bed.

After performing a series of batch type experiments using a lab-scale combustor, consideration was given to the use of an internally cycloned circulating fluidized bed combustor (ICCFBC) for a paper mill sludge. Operation parameters including water content, feeding mass of the sludge, and secondary air injection ratio were varied to understand their effects on combustion performance, which was examined in terms of carbon conversion rate (CCR) and the emission rates of CO, C(x)H(y) and NO(x). The combustion of paper mill sludge in the ICCFBC was compared to the reaction mechanisms of a conventional solid fuel combustion, characterized by kinetics limited reaction zone, diffusion limited reaction zone, and transition zone. The results of the parametric study showed that a 35% water content and 60 g feeding mass generated the best condition for combustion. Meanwhile, areal mass burning rate, which is an important design and operation parameter at an industrial scale plant, was estimated by a conceptual equation. The areal mass burning rate corresponding to the best combustion condition was approximately 400 kg/hm(2) for 35% water content. The secondary air injection generating swirling flow enhanced the mixing between the gas phase components as well as the solid phase components, and improved the combustion efficiency by increasing the carbon conversion rate and reducing pollutant emissions.

Air Pollutants↗

PubMed2005

Comparison of alfetanil and ketamine in combination with propofol for patient-controlled sedation during fiberoptic bronchoscopy.

BACKGROUND: During fiberoptic bronchoscopy, propofol, ketamine, benzodiazepines, and opiates are most commonly used, alone or in combination for sedation. The aim of this study was to compare the clinical efficacy of propofol/ketamine with propofol/alfentanil for patient-controlled sedation (PCS) during fiberoptic bronchoscopy. METHOD: Patients undergoing fiberoptic bronchoscopy were randomly assigned to receive either propofol/alfentanil (PA group; n = 138) or propofol/ketamine (PK group; n = 138) via a patient-controlled analgesia (PCA) device for sedation and analgesia. Changes in blood pressure, heart rate (HR), and oxygen saturation were monitored. Degree of patient and bronchoscopist satisfaction was evaluated using a 10-cm visual analog scale (VAS) (0 = extremely uncomfortable to 10 = extremely comfortable). RESULTS: After sedation, systolic arterial pressure (SAP) decreased in the PA group, but SAP was stable in the PK group. Compared with values immediately before starting bronchoscopy, SAP and HR increased during the procedure in both groups (P < 0.05). Patients in the PK group showed more satisfaction [(9.5 (6-10) vs. 9.0 (6-10)), P < 0.05] and amnesia (82% vs. 61%, P < 0.01). Despite these differences, the majority (greater than 90%) of the patients in both groups stated that they were comfortable during the procedure. CONCLUSION: Our results show that although both techniques proved effective for sedation in patients undergoing fiberoptic bronchoscopy, ketamine is superior to alfentanil when used in combination with propofol because of the high patient satisfaction and amnesia.

Adolescent↗

PubMed2004

High-transition-temperature superconductivity in the absence of the magnetic-resonance mode.

The fundamental mechanism that gives rise to high-transition-temperature (high-T(c)) superconductivity in the copper oxide materials has been debated since the discovery of the phenomenon. Recent work has focused on a sharp 'kink' in the kinetic energy spectra of the electrons as a possible signature of the force that creates the superconducting state. The kink has been related to a magnetic resonance and also to phonons. Here we report that infrared spectra of Bi2Sr2CaCu2O8+delta (Bi-2212), shows that this sharp feature can be separated from a broad background and, interestingly, weakens with doping before disappearing completely at a critical doping level of 0.23 holes per copper atom. Superconductivity is still strong in terms of the transition temperature at this doping (T(c) approximately 55 K), so our results rule out both the magnetic resonance peak and phonons as the principal cause of high-T(c) superconductivity. The broad background, on the other hand, is a universal property of the copper-oxygen plane and provides a good candidate signature of the 'glue' that binds the electrons.

Journal Article↗

PubMed2004

An unusual cause of pulmonary haemorrhage in a patient with rheumatoid arthritis.

INTRODUCTION: Pulmonary haemorrhage is a rare presentation of strongyloides hyperinfection. CLINICAL PICTURE: A 69-year-old female patient with rheumatoid arthritis on methotrexate and prednisolone presented with severe community acquired pneumonia. Intravenous trimethoprim/ sulfamethoxazole (bactrim) and high dose hydrocortisone for Pneumocystis carinii pneumonia were commenced. She developed pulmonary haemorrhage 2 weeks later and bronchoalveolar lavage cytology revealed helminthic larvae identified as strongyloides. TREATMENT AND OUTCOME: Despite treatment with ivermectin and albendazole with rapid tailing down of hydrocortisone, she succumbed to her illness. CONCLUSIONS: Strongyloides hyperinfection should be considered in an immunocompromised patient on high dose corticosteroid presenting with pulmonary haemorrhage. Prognosis remains dismal as supported by our case report and current literature.

Aged↗

PubMed2003

Measuring local optical properties: near-field polarimetry of photonic block copolymer morphology.

Ultrahigh molecular weight polystyrene-b-polyisoprene block copolymers (BCs), noted for their photonic behavior, were imaged using transmission near-field scanning optical microscopy (NSOM) and NSOM polarimetry. Our improved scheme for polarization modulation (PM) polarimetry, which accounts for optical anisotropies of the NSOM aperture probe, enables mapping of the local diattenuation and birefringence (with separately aligned diattenuating and fast axes) in these specimens with subdiffraction limited resolution. PM-NSOM micrographs illuminate the mesoscopic optical nature of these BC specimens by resolving individual microphase domains and defect structures.

Butadienes↗

PubMed2001

A randomized study of the utility of human immunodeficiency virus RNA measurement for the management of antiretroviral therapy.

To compare frequent measurement with infrequent measurement of human immunodeficiency virus (HIV) RNA levels in the management of antiretroviral therapy, we conducted a clinical strategy study of 206 HIV-infected patients who had <500 CD4 cells/mm(3). Patients were randomized (1.5:1) to undergo frequent monitoring (at baseline and every 2 months) or infrequent monitoring (at baseline and twice yearly), with CD4 cell counts determined every 2 months. Patients received unrestricted antiretroviral therapy. In the primary analysis (at month 6), the frequent group had a mean HIV RNA reduction (+/- standard deviation) of 0.93+/-0.79 log(10) copies/mL, versus 0.48+/-0.83 log(10) copies/mL for the infrequent group (P=.0002). A trend (P=.1) toward improved survival was seen in the frequent group. Given this improved virological response, more frequent HIV RNA measurement than is recommended in published guidelines (every 3-4 months) may be appropriate.

Adult↗

PubMed2001

26 S proteasome-mediated degradation of topoisomerase II cleavable complexes.

DNA topoisomerase II (TOP2) cleavable complexes represent an unusual type of DNA damage characterized by reversible TOP2-DNA cross-links and DNA double strand breaks. Many antitumor drugs and physiological stresses are known to induce TOP2 cleavable complexes leading to apoptotic cell death and genomic instability. However, the molecular mechanism(s) for repair of TOP2 cleavable complexes remains unclear. In the current studies, we show that TOP2 cleavable complexes induced by the prototypic TOP2 poison VM-26 are proteolytically degraded by the ubiquitin/26 S proteasome pathway. Surprisingly the TOP2beta isozyme is preferentially degraded over TOP2alpha isozyme. In addition, transcription inhibitors such as 5,6-dichlorobenzimidazole riboside and camptothecin can substantially block VM-26-induced TOP2beta degradation. These results are consistent with a model in which the repair of TOP2beta cleavable complexes may involve transcription-dependent proteolysis of TOP2beta to reveal the protein-concealed double strand breaks.

Animals↗

PubMed2001

Hepatic hyperplasia in noncirrhotic fatty livers: is obesity-related hepatic steatosis a premalignant condition?

It is not known whether obesity increases the risk for hepatocellular carcinoma (HCC) simply because it promotes cirrhosis, a general risk factor for HCC, or via some other mechanism that operates independently of cirrhosis. If the latter occurs, then hepatocyte hyperplasia, an early event during the neoplastic process, might begin before liver cirrhosis develops. Genetically obese, leptin-deficient ob/ob mice are models for nonalcoholic fatty liver disease (NAFLD), a type of liver disease that is strongly associated with obesity and type 2 diabetes. Similar to obese, diabetic patients, ob/ob mice have an increased incidence of HCC. However, unlike humans with NAFLD, they rarely, if ever, develop cirrhosis spontaneously. To determine whether the noncirrhotic livers of ob/ob mice with NAFLD exhibit hepatocyte hyperplasia, parameters of proliferation and apoptosis were compared in adult ob/ob mice and their healthy litter mates. Adult ob/ob mice have an increase in liver mass relative to body mass. This hepatomegaly cannot be explained solely by lipid accumulation and is accompanied by significant increases in hepatocyte proliferative activity (as evidenced by increased Erk activation, cell-cycle related gene expression, bromodeoxyuridine incorporation, and hepatic DNA content) with concomitant inhibition of hepatocyte apoptosis (as evidenced by decreased numbers of apoptotic hepatocytes, induction of several antiapoptotic mechanisms, and decreased activation of procaspase 3). Thus, liver hyperplasia is evident at the earliest stage of NAFLD in ob/ob mice, which supports the concept that obesity-related metabolic abnormalities, rather than cirrhosis, initiate the hepatic neoplastic process during obesity.

Animals↗

PubMed2001

An essential GTPase, der, containing double GTP-binding domains from Escherichia coli and Thermotoga maritima.

A gene encoding a putative GTPase containing two tandemly repeated GTP-binding domains from a hyperthermophilic bacterium, Thermotoga maritima, was cloned and expressed in Escherichia coli. The gene (TM1446) termed der is highly conserved in Eubacteria including E. coli. The purified der product (Tm-Der) has GTPase activity but no ATPase activity. GTP, GDP, and dGTP but not GMP, ATP, CTP, and UTP compete for GTP binding to Tm-Der. An optimal condition for the GTPase assay was determined to be pH 7.5 in 400 mm KCl and 5 mm MgCl(2) at 70 degrees C, where K(m), V(max), and k(cat) values were determined to be 110 microm, 3.46 microm/min, and 0.87 min(-1), respectively. A der deletion strain of E. coli was constructed by replacing the der gene (originally annotated yfgK) with a kanamycin resistance gene. The deletion strain was found to form colonies only if the cells harbored a plasmid containing der, indicating that der is essential for E. coli growth.

Amino Acid Sequence↗

PubMed2001

Real-time volume rendering of four-dimensional images based on three-dimensional texture mapping.

A four-dimensional (4-D) image consists of three-dimensional (3-D) volume data that varies with time. It is used to express a deforming or moving object in virtual surgery or 4-D ultrasound. It is difficult to obtain 4-D images by conventional ray-casting or shear-warp factorization methods because of their time-consuming rendering process and the pre-processing stage necessary whenever the volume data are changed. Even when 3-D texture mapping is used, repeated volume loading is time-consuming in 4-D image rendering. In this study, we propose a method to reduce data loading time using coherence between currently loaded volume and previously loaded volume in order to achieve real-time rendering based on 3-D texture mapping. Volume data are divided into small bricks and each brick being loaded is tested for similarity to one that was already loaded in memory. If the brick passes the test, it is defined as 3-D texture by OpenGL functions. Later, the texture slices of the brick are mapped into polygons and blended by OpenGL blending functions. All bricks undergo this test. Using continuous deforming, 50 volumes are rendered in interactive time with SGI ONYX. Realtime volume rendering based on 3-D texture mapping is currently available for personal computers.

Humans↗

PubMed2001

Methylated mono- and di(ethylene glycol)-functionalized beta-sheet forming polypeptides.

We have synthesized methylated mono- and di(ethylene glycol)-functionalized polymers of L-serine and L-cysteine that adopt beta-sheet conformations in the solid state: poly(O-(2-(2-methoxyethoxy)ethyl)-L-serine), poly(1); poly(O-(2-(methoxy)ethyl)-L-serine), poly(2); and poly(S-(2-(2-methoxyethoxy)ethoxy)carbonyl-L-cysteine), poly(3). Of these three polymers, only poly(1) was found to be highly soluble in water independent of pH. Circular dichroism analysis of poly(1) in water or trifluoroethanol at 25 degrees C revealed that it is in a random conformation, which was unperturbed by changes in pH, buffer, or temperature. However, addition of methanol or acetonitrile to aqueous solutions of poly(1) resulted in a transition to the beta-sheet conformation, as found in the solid state. The polymers were synthesized by transition metal catalyzed polymerization of amino acid-N-carboxyanhydrides, prepared from the functionalized amino acids and represent a new class of readily processable beta-sheet forming polypeptides.

Buffers↗

PubMed2001

Soy and alfalfa phytoestrogen extracts become potent low-density lipoprotein antioxidants in the presence of acerola cherry extract.

Postmenopausal women have an increased risk of coronary heart disease. Oxidation of low-density lipoprotein (LDL) has been implicated in atherogenesis, and the presence of modified LDL (LDL(-)) in plasma appears to represent LDL oxidation in vivo. Because previous studies have demonstrated a strong antiatherogenic effect of estrogen due to its antioxidant activity and similar antioxidant activity was found for specific isoflavones derived from soy extract, the antioxidant activity of a phytoestrogen extract derived from soy and alfalfa was studied. Copper-mediated LDL oxidation was inhibited in the presence of soy and alfalfa extracts, and this effect was further enhanced in the presence of acerola cherry extract, which is rich in ascorbic acid. Male rabbit aortic endothelial cells pretreated with soy extract were resistant to the toxic effects of high levels of LDL and LDL(-), and a lesser, but significant protection, was also afforded by alfalfa extract. Cell-mediated oxidation of LDL, measured by LDL(-) formation, was inhibited in the presence of soy extract but not alfalfa extract. However, in the presence of acerola cherry extract, both soy and alfalfa extracts potently inhibited the formation of LDL(-). These findings show that acerola cherry extract can enhance the antioxidant activity of soy and alfalfa extracts in a variety of LDL oxidation systems. The protective effect of these extracts is attributed to the presence of flavonoids in soy and alfalfa extracts and ascorbic acid in acerola cherry extract, which may act synergistically as antioxidants. It is postulated that this synergistic interaction among phytoestrogens, flavonoids, and ascorbic acid is due to the "peroxidolitic" action of ascorbic acid, which facilitates the copper-dependent decomposition of LDL peroxides to nonradical products; this synergy is complemented by a mechanism in which phytoestrogens stabilize the LDL structure and suppress the propagation of radical chain reactions. The combination of these extracts markedly lowers the concentrations of phytoestrogens required to achieve significant antioxidant activity toward LDL.

Adult↗

PubMed2001

A MATE family multidrug efflux transporter pumps out fluoroquinolones in Bacteroides thetaiotaomicron.

We cloned a gene, bexA, that codes for a multidrug efflux transporter from the chromosomal DNA of Bacteroides thetaiotaomicron ATCC 29741 by using an Escherichia coli DeltaacrAB DeltaacrEF mutant as a host. Although the initial recombinant construct contained other open reading frames, the presence of bexA alone was sufficient to confer to the E. coli host elevated levels of resistance to norfloxacin, ciprofloxacin, and ethidium bromide. Disruption of bexA in B. thetaiotaomicron made the strain more susceptible to norfloxacin, ciprofloxacin, and ethidium bromide, showing that this gene is expressed in this organism and functions as a multidrug efflux pump. The deduced BexA protein sequence was homologous to the protein sequence of Vibrio parahaemolyticus NorM, a multidrug efflux transporter, and thus, BexA belongs to the multidrug and toxic compound extrusion (MATE) family.

ATP-Binding Cassette Transporters↗

PubMed2001

Structure-function analysis of BfpB, a secretin-like protein encoded by the bundle-forming-pilus operon of enteropathogenic Escherichia coli.

Production of type IV bundle-forming pili by enteropathogenic Escherichia coli (EPEC) requires BfpB, an outer-membrane lipoprotein and member of the secretin protein superfamily. BfpB was found to compose a ring-shaped, high-molecular-weight outer-membrane complex that is stable in 4% sodium dodecyl sulfate at temperatures of < or = 65 degrees C. Chemical cross-linking and immunoprecipitation experiments disclosed that the BfpB multimeric complex interacts with BfpG, and mutational studies showed that BfpG is required for the formation and/or stability of the multimer but not for the outer-membrane localization of BfpB. Formation of the BfpB multimer also does not require BfpA, the repeating subunit of the pilus filament. Functional studies of the BfpB-BfpG complex revealed that its presence confers vancomycin sensitivity, indicating that it may form an incompletely gated channel through the outer membrane. BfpB expression is also associated with accumulation of EPEC proteins in growth medium, suggesting that it may support both pilus biogenesis and protein secretion.

Amino Acid Sequence↗