Analysis of angularly dependent ODNMR spectra of 151Eu3+ in LaF3.
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Journal Article↗
Biomedical subjects
J Huang
Publications and source records attributed to J Huang.
Cellular responses of cultured cerebellar astrocytes to ethacrynic acid-induced perturbation of subcellular glutathione homeostasis.
Glutathione (GSH) and glutathione-related enzyme systems in astrocytes play an important role in cellular defense against oxidative stress in the nervous system. The present study was designed to characterize the cellular responses of cultured astrocytes to chemically-induced perturbations of mitochondrial and cytosolic GSH homeostasis. Treatment of astrocytes in culture with ethacrynic acid (EA), a mitochondrion-penetrating thiol reagent, induced rapid and extensive depletion of both cytosolic and mitochondrial pools of GSH. Concomitant with the effects of EA on cellular GSH were significant and concentration-dependent increases in intracellular generation of reactive oxygen species (ROS) as indicated by the oxidation of preloaded 2',7'-dichlorofluorescein diacetate. Significant elevation of intracellular ROS occurred by 15 min following exposure to 100 microM EA and reached peak levels by 30 min which were approximately 7-fold higher than corresponding control levels. Ethacrynic acid-induced GSH depletion and intracellular ROS elevation was followed by marked decreases in glutathione reductase (GR) activity in mitochondria, and to a lesser extent, in cytosolic fractions of cultured astrocytes. This inhibitory effect was time- and concentration-dependent, and other GSH-related enzymes, glutathione peroxidase and glutathione S-transferase, were not or only slightly affected. Kinetic studies showed that EA markedly diminished V(max) values of both mitochondrial and cytosolic GR without affecting K(m), suggesting noncompetitive inhibition of this thiol-dependent enzyme. Another thiol-dependent enzyme glyceraldehyde-3-phosphate dehydrogenase was also markedly inhibited by EA in a time-dependent fashion. Subsequent decline of mitochondrial transmembrane potential (rhodamine 123 uptake) and cellular ATP production following EA treatment occurred prior to the onset of loss of cell viability as indicated by lactate dehydrogenase leakage. These results suggest that the loss of mitochondrial GSH may render the astrocytes unable to combat the pathological sequelae of endogenous oxidative stress, leading to perturbations of thiol-dependent enzyme activities, mitochondrial function and energy metabolism.
Animals↗
Hydrogen bonding of tyrosine B10 to heme-bound oxygen in Ascaris hemoglobin. Direct evidence from UV resonance Raman spectroscopy.
The hemoglobin from Ascaris suum, a parasitic nematode, has a spontaneous dissociation rate for the dioxygen ligand that is 3 orders of magnitude less than for mammalian myoglobins or hemoglobins. In this hemoglobin, the distal histidine is replaced with a glutamine which is capable of forming a stabilizing hydrogen bond to the bound dioxygen. A single hydrogen bond from a glutamine is, under typical circumstances, not sufficient to account for the low off rate for oxygen. Several studies point to a second hydrogen bond to the heme-bound dioxygen originating from tyrosine B10 as the source of this unusual reactivity. In this study ultraviolet (UV) resonance Raman spectroscopy is used to directly observe the formation of this hydrogen bond upon oxygen binding. The study reveals that both oxygen and carbon monoxide induce similar conformational changes in the globin upon binding to the heme; however, in the case of oxygen, a strong hydrogen bond involving a tyrosine is also observed. Similar studies on the QE7L mutant of this Hb suggest that the glutamine plays a role in stabilizing a rigid tertiary structure associated with the distal heme pocket. This conformation maintains the tyrosine in an orientation conducive to hydrogen bond formation with a heme-bound dioxygen ligand.
Animals↗
Stress analysis of a bulk-filled Class-V chemical-cured dental composite restoration.
Clinical problems associated with the polymerization shrinkage of dental composite restorations include tooth sensitivity, crown fracture, discoloration, recurrent decay, and loss of restoration. Our goal was to determine whether these complications could be attributed to the transient stresses developed during contraction. Thus, a finite element model was used to calculate the transitory deformations and composite-tooth interface stresses produced during the shrinkage of a chemical-cured ideal Class-V composite restoration. It was found that the interface stress peaks moved with the polymerization front, and that in some instances, their intermediate magnitudes were higher than the final, fully cured, values. Therefore, the results indicate that clinical failure may be related to these transitory changes during the polymerization process.
Dental Materials↗
Membranous nephropathy, interstitial nephritis, and Fanconi syndrome-- glomerular antigen.
We characterized the glomerular antigen of membranous nephropathy (MN) in a child with the triad of MN, proximal renal tubular basement membrane autoantibody (TBMAb)-associated interstitial nephritis (ITN), and Fanconi syndrome. Granular staining was demonstrated for human gp600 in the vicinity of immune deposits of MN along glomerular capillary loops, using a monospecific polyclonal antibody to human gp600 by indirect immunofluorescence. However, no staining was observed in the MN deposits for receptor-associated protein. Membranous nephropathy preceded the development of TBMAbs, ITN, and Fanconi syndrome by 1 year, showing that the MN lesion does not result from the initial immunological injury to the tubulointerstitium, as postulated earlier. We confirmed the reactivity of TBMAbs with the recently described rabbit 58-kilodalton (kDa) tubular basement membrane antigen (TBMAg). However, this is the first report to show reactivity of these antibodies with the human 58-kDa protein. Also, we found that TBMAg is comprised of a single protein band of 58 kDa, unlike the previously described combination of two protein band (58 kDa and 175 kDa). In this patient, following prednisone treatment, the TBMAbs became undetectable, and the nephrotic syndrome and Fanconi syndrome resolved, thus suggesting a causal role of TBMAbs in the pathogenesis of Fanconi syndrome. We postulate that in this rare disorder, renal lesions result from an autoimmune response to the 58-kDa TBMAg and possibly to gp600, and that the predisposition to autoimmunity is genetically linked to the HLA B7 serotype.
Anti-Inflammatory Agents↗
Lump detection is enhanced in silicone breast models simulating postmenopausal breast tissue.
We varied the softness and nodularity of silicone breast models to assess the effects of age-related breast tissue characteristics on lump detection. In two sets of six silicone breast models manufactured to simulate premenopausal and postmenopausal breast tissue, respectively, 82 internal medicine attending and housestaff physicians more readily detected lumps among models simulating older breast tissue. The proportion of models with one or more false-positive findings was higher among models simulating postmenopausal breast tissue. We conclude that age-related changes in breast tissue most likely contribute to the higher sensitivity of clinical breast examination in older women.
Adult↗
Cesium stress and adaptation in Pseudomonas fluorescens.
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Cesium↗
Mechanism of chromium detoxification in Pseudomonas fluorescens is dependent on iron.
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Biodegradation, Environmental↗
Near-infrared spectra of Scapharca homodimeric hemoglobin: characterization of the deoxy and photodissociated derivatives.
The near-infrared charge transfer band at 760 nm (band III) has been investigated in deoxy and photodissociated dimeric Scapharca hemoglobin. At 300 K, the 10-ns spectrum of the carbonmonoxy derivative photoproduct is shifted by about 6 nm toward longer wavelengths with respect to the deoxy spectrum, both in buffer and in glycerol/buffer solutions. Moreover, the band III peak occurs at about the same wavelength at 300 K and at 10 K for the 10-ns photodissociated derivative, whereas in the deoxy derivative large changes in peak position and linewidth are observed as a function of temperature. These findings suggest that in dimeric Scapharca hemoglobin the photoproduct has not relaxed after 10 ns. The complete time dependence of the relaxation process has been studied both in buffer and in glycerol/buffer solutions at room temperature. The relaxation from the photoproduct to the deoxy species occurs on a microsecond time scale, in line with recent optical absorption and resonance Raman measurements.
Animals↗
Decreased ventilatory response to hypoxia in sedated newborn piglets prenatally exposed to cocaine.
OBJECTIVE: Infants exposed to cocaine in utero have been reported to have a higher incidence of apnea and altered ventilatory response to carbon dioxide and hypoxia. We investigated whether in utero cocaine exposure results in greater ventilatory depression during hypoxia in piglets. METHODS: Cocaine hydrochloride, 1.0 or 2.0 mg/kg given intramuscularly, or saline solution was administered daily to pair-fed pregnant sows during the last month of gestation. Thirteen cocaine-exposed piglets (mean +/- SD: age, 4.4 +/- 1.3 days; weight, 2.10 +/- 0.10 kg) and 15 saline solution-exposed piglets (age, 4.6 +/- 1.1 days; weight, 2.32 +/- 0.42 kg) were studied under chloral hydrate sedation. Minute ventilation (VE), arterial blood pressure (BP), heart rate (HR), oxygen consumption (VO2), and arterial blood gases were measured in room air. During hypoxia (fraction of inspired oxygen = 0.10), the values for VE, BP, and HR were obtained at 1, 5, and 10 minutes, VO2 was calculated during the last 5 minutes, and arterial blood gas samples taken after 10 minutes. RESULTS: Basal VE did not differ between saline solution- and cocaine-exposed animals. The increase in VE at 1 minute of hypoxia was also similar. However, at 5 and 10 minutes of hypoxia, VE was significantly lower in the cocaine group than in the saline group (6% +/- 9% and 4% +/- 10% vs 15% +/- 13% and 21% +/- 14%; p < 0.02). Mean baseline BP and the initial increase in BP during hypoxia were not different between groups. However, BP remained increased throughout hypoxia only in the saline solution-exposed animals (p < 0.05). Changes in HR, VO2, arterial oxygen tension, and base excess during hypoxia were similar between groups. CONCLUSIONS: These results show a decrease in the ventilatory response to hypoxia in newborn piglets prenatally exposed to cocaine. This change is most likely to be centrally mediated because the initial hypoxic hyperventilation was not modified by the intrauterine cocaine exposure. This decrease in ventilation cannot be explained by changes in metabolic rate or in cardiovascular or acid-base status.
Animals↗
Total and functional antibody response to a quadrivalent meningococcal polysaccharide vaccine among children.
OBJECTIVE: To determine total and functional serogroup C antibody response after vaccination with a quadrivalent meningococcal polysaccharide vaccine. DESIGN: Prospective, before and after intervention study. SUBJECTS: Study subjects were between the ages of 0.5 and 19.9 years, and were eligible for a community-wide public health immunization campaign against Neisseria meningitidis serogroup C. METHODS: Total and functional antibody response was measured by enzyme-linked immunosorbent assay and bactericidal assay, respectively. RESULTS: One month after vaccination, total capsular polysaccharide antibody significantly increased in all age groups; a significant rise in bactericidal antibody, that correlated with total capsular polysaccharide antibody, was seen in children 18 months of age and older. At 1 year bactericidal antibody titers were maintained but capsular polysaccharide antibody declined substantially in children younger than 5 years. CONCLUSION: Total capsular polysaccharide antibody concentration appears to be a useful surrogate measure of bactericidal antibody in children 18 months and older. Children who originally received the vaccine at less than 18 months of age should be considered for revaccination if there is a new or continuing risk of disease. Because of the differences in the total and bactericidal antibodies formed, vaccine efficacy trials are required to define which serologic measures are associated with protection.
Adolescent↗
TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex.
The death domain of tumor necrosis factor (TNF) receptor-1 (TNFR1) triggers distinct signaling pathways leading to apoptosis and NF-kappa B activation through its interaction with the death domain protein TRADD. Here, we show that TRADD interacts strongly with RIP, another death domain protein that was shown previously to associate with Fas antigen. We also show that RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process. Overexpression of the intact RIP protein induces both NF-kappa B activation and apoptosis. However, expression of the death domain of RIP Induces apoptosis, but potently inhibits NF-kappa B activation by TNF. These results suggest that distinct domains of RIP participate in the TNF signaling cascades leading to apoptosis and NF-kappa B activation.
Amino Acid Sequence↗
Clinical economics review: cost-effectiveness of treatment alternatives for gastro-oesophageal reflux disease.
Gastro-oesophageal reflux disease is a chronic recurring disorder, which is widespread, especially in Western societies. Faced with increasing health costs and finite resources, an increasingly important part of evaluating new treatments is economic appraisal. In this paper, we review critically the published economic studies of the cost-effectiveness of treatments for gastro-oesophageal reflux disease. Proton pump inhibitors are considered the best choice for the management of grades II-IV oesophagitis and are more cost-effective than H2-receptor antagonists because of their fast healing of oesophagitis, early relief of symptoms, and prevention of recurrent oesophagitis and development of complications.
Cost-Benefit Analysis↗
Cloning and characterization of tek, the gene encoding the major extracellular protein of Pseudomonas solanacearum.
Susceptible plants infected by Pseudomonas solanacearum usually will, largely due to extracellular proteins (EXPs) and the high-molecular-mass extracellular polysaccharide (EPS I) this pathogen produces. Circumstantial evidence suggested that a 28-kDa protein, the single most abundant EXP made by P. solanacearum in culture, is associated with production of EPS I, and thus might have a role in pathogenesis. The 28-kDa EXP was purified and, based on its N-terminal amino acid sequence, an oligonucleotide mixture was made and used as a hybridization probe to clone the gene encoding it. DNA sequence analysis suggested that the coding sequence for the 28-kDa EXP is within a gene, designated tek, that encodes a 58-kDa membrane-associated precursor protein that is processed by signal peptidase II during export. Analysis of radiolabeled polypeptides expressed from tek confirmed that it encodes a 58-kDa precursor protein, which is exported out of the cells as a 55-kDa preprotein and processed extracellularly to release the very basic 28-kDa EXP from its C terminus. The position, transcriptional direction, and regulated expression of tek suggest that it is cotranscribed with xpsR, a gene essential for regulating biosynthesis of EPS I, and reinforces the association of the 28-kDa EXP with virulence. However, since P. solanacearum mutants lacking only the 28-kDa EXP produced wild-type amounts of EPS I and were fully virulent, the function of this protein remains unclear.
Amino Acid Sequence↗
Comorbidity-adjusted complication risk: a new outcome quality measure.
The measurement of inpatient complications his received substantial attention in recent years because mortality rates and other outcome measures often appear unable to discriminate superior from inferior hospital care. Complication measurement holds out the promise of being more sensitive to variations in patient care because complications occur more frequently than do mortalities, and because complications are more direct consequences of the process of care. The authors developed a new measure of complications that seeks to give insight into the patient care given by different hospitals or physicians by using commonly available data. Specifically, this measure is based on a decision-theoretic model that estimates the probability of a complication for combinations of admitting and secondary International Classification of Diseases, 9th Revision, Clinical Modification diagnoses. The measure can be evaluated at the patient level, or aggregated and risk-adjusted for the population of a given care provider (eg, physician or hospital). When applied to a set of patient-level UB- 82/92 data, this measure estimates the risk of complication for any member of a population, controlling for comorbidity, and hence is designated comorbidity-adjusted complication risk (CACR). The authors describe the development of CACR and its testing and validation using data acquired from the states of Pennsylvania, California, and Florida, as well as facility data obtained directly from hospitals. The data set includes 480,000 patients from 50 Pennsylvania hospitals, 300,000 patients from 33 Florida hospitals, 370,000 patients from 35 California hospitals, and 37,000 patients from six validation hospitals. Comorbidity-adjusted complication risk is constructed from widely available data common to most patient cases. Comorbidity-adjusted complication risk can be adjusted for its case mix, but such risk adjustment has much less effect on CACR than on other adverse outcomes such as mortality and morbidity. Comorbidity-adjusted complication risk varies widely across the hospitals in this sample, yet it is stable across time and is correlated with other known quality outcomes, including such accepted "gold standards" as hospital-documented adverse event rates and chart review determinations of complications.
Aged↗
Pattern formation and evolution near autocatalytic reaction fronts in a narrow vertical slab.
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Journal Article↗
Pediocin 5 production and plasmid stability during continuous free and immobilized cell cultures of Pediococcus acidilactici UL5.
Continuous production of pediocin 5 from Pediococcus acidilactici UL5 was investigated in MRS medium at different pH and dilution rates during continuous free cell (FC) and immobilized cell (IC) fermentations. Pediocin 5 activity from FC operated at a dilution rate of 0.31 h-1 largely increased from 128 to 2048 AU mL-1 as pH decreased from 7.0 to 5.0. Pediocin 5 activity in IC at a dilution rate of 0.93 h-1 was much less affected by pH, varying from 256 AU mL-1 at pH 7.0 to 512 AU mL-1 at pH 5.0. At the optimum pH 5.0, the dilution rate greatly influenced pediocin 5 activity both in FC and IC. Pediocin 5 production during continuous FC culture decreased with time for all dilution rates tested except 0.31 h-1 and average activity over 144 h cultures reached a maximal value of 4915 AU mL-1 at a dilution rate of 0.26 h-1. For IC, pediocin 5 production was stable with time and increased with the dilution rate from 256 to 1024 AU mL-1 in the range of 0.47-2.28 h-1. Three Listeria strains were tested for their ability to screen low bacteriocin-producing variants (Bac+v) of Bac+ cells in FC and IC cultures by using a modified deferred antagonism method. Ten to 28% of Bac+v cells appeared after 144 h of FC cultures at dilution rates in the range 0.09-0.42 h-1 and pH control set points of 5.0-7.0 while almost no Bac+v cell was detected during 192 h IC culture in the same pH range and for dilution rates varying from 0.47 to 2.28 h-1. The Bac+v cells isolated produced eight- to 64-fold less pediocin 5 than the Bac+ cells. Although electrophoresis analysis showed no apparent difference in the plasmid profiles of Bac+v and Bac+ cells, the Bac- mutant obtained by acriflavine treatment had lost the pMJ5 plasmid encoding for bacteriocin production. The decreased quantity of plasmid DNA in Bac+v cells suggests that the decreased pediocin 5 activity of Bac+v cells resulted from a decrease in plasmid copy number.
Bacteriocins↗
Interaction between FtsZ and inhibitors of cell division.
The interaction between inhibitors of cell division and FtsZ were assessed by using the yeast two-hybrid system. An interaction was observed between FtsZ and SulA, a component of the SOS response, and the interacting regions were mapped to their conserved domains. This interaction was reduced by mutations in sulA and by most mutations in ftsZ that make cell refractory to sulA. No interaction was detected between FtsZ and MinCD, an inhibitory component of the site selection system. However, interactions were observed among various members of the Min system, and MinE was found to reduce the interaction between MinC and MinD. The implications of these findings for cell division are discussed.
Adenosine Triphosphatases↗