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Biomedical subjects

T Liu

Publications and source records attributed to T Liu.

At least 91 records · Page 5Linked to original sources
PubMed2001

Aberrant metal binding by prion protein in human prion disease.

Human prion diseases are characterized by the conversion of the normal prion protein (PrP(C)) into a pathogenic isomer (PrP(Sc)). Distinct PrP(Sc) conformers are associated with different subtypes of prion diseases. PrP(C) binds copper and has antioxidation activity. Changes in metal-ion occupancy can lead to significant decline of the antioxidation activity and changes in conformation of the protein. We studied the trace element status of brains from patients with sporadic Creutzfeldt-Jakob disease (sCJD). We found a decrease of up to 50% of copper and an increase in manganese of approximately 10-fold in the brain tissues from sCJD subjects. We have also studied the metal occupancy of PrP in sCJD patients. We observed striking elevation of manganese and, to a lesser extent, of zinc accompanied by significant reduction of copper bound to purified PrP in all sCJD variants, determined by the PrP genotype and PrP(Sc) type, combined. Both zinc and manganese were undetectable in PrP(C) preparations from controls. Copper and manganese changes were pronounced in sCJD subjects homozygous for methionine at codon 129 and carrying PrP(Sc) type-1. Anti-oxidation activity of purified PrP was dramatically reduced by up to 85% in the sCJD variants, and correlated with increased in oxidative stress markers in sCJD brains. These results suggest that altered metal-ion occupancy of PrP plays a pivotal role in the pathogenesis of prion diseases. Since the metal changes differed in each sCJD variants, they may contribute to the diversity of PrP(Sc) and disease phenotype in sCJD. Finally, this study also presented two potential approaches in the diagnosis of CJD; the significant increase in brain manganese makes it potentially detectable by MRI, and the binding of manganese by PrP in sCJD might represent a novel diagnostic marker.

Antioxidants↗
PubMed2001

Oxidative impairment in scrapie-infected mice is associated with brain metals perturbations and altered antioxidant activities.

Prion diseases are characterized by the conversion of the normal cellular prion protein (PrP(C)) into a pathogenic isoform (PrP(Sc)). PrP(C) binds copper, has superoxide dismutase (SOD)-like activity in vitro, and its expression aids in the cellular response to oxidative stress. However, the interplay between PrPs (PrP(C), PrP(Sc) and possibly other abnormal species), copper, anti-oxidation activity and pathogenesis of prion diseases remain unclear. In this study, we reported dramatic depression of SOD-like activity by the affinity-purified PrPs from scrapie-infected brains, and together with significant reduction of Cu/Zn-SOD activity, correlates with significant perturbations in the divalent metals contents. We also detected elevated levels of nitric oxide and superoxide in the infected brains, which could be escalating the oxidative modification of cellular proteins, reducing gluathione peroxidase activity and increasing the levels of lipid peroxidation markers. Taken together, our results suggest that brain metal imbalances, especially copper, in scrapie infection is likely to affect the anti-oxidation functions of PrP and SODs, which, together with other cellular dysfunctions, predispose the brains to oxidative impairment and eventual degeneration. To our knowledge, this is the first study documenting a physiological connection between brain metals imbalances, the anti-oxidation function of PrP, and aberrations in the cellular responses to oxidative stress, in scrapie infection.

Animals↗
PubMed2001

An evaluation of a polyethersulfone hollow fiber plasma separator by animal experiment.

Membrane plasma separators are being used routinely for therapy in various diseases. In this study, a newly developed plasma separator made of polyethersulfone (PES) hollow fibers was evaluated for its plasma filtration efficiency and blood compatibility by animal experiment. Hemolysis did not occur under the usual conditions of plasma separation. The sieving coefficients of total protein and albumin were over 95%, and the total cholesterol was over 90% throughout the perfusions. Decreases in white blood cells, platelets, fibrinogen, and coagulation factors were observed during the early stage of plasma separation, but appear to be within acceptable ranges for clinical use.

Animals↗
PubMed2001

Can emergency department triage nurses predict patients' dispositions?

Early recognition of inpatient bed requirements might be helpful in expediting the admission process through the emergency department (ED). With this in mind, we asked whether ED triage nurses could accurately predict patients' in-hospital dispositions. A prediction was recorded for 521 ED patients, of whom 107 (20.5%) were ultimately admitted to the hospital. Nurses correctly anticipated 66 of 107 hospital admissions (sensitivity = 61.7%, PPV = 61.7%). With respect to predicting specific levels of inpatient care, nurses correctly anticipated 17 of 45 floor admissions (sensitivity = 37.8%, PPV = 34.7%), 14 of 33 step-down/monitored unit admissions (sensitivity = 42.4%, PPV = 48.3%), and 12 of 24 intensive care unit admissions (sensitivity = 50.0%, PPV = 66.7%). Lacking in sensitivity and positive predictive value, particularly with regard to specific levels of inpatient care, triage nurses' predictions may have limited potential to expedite the admission process.

Emergency Service, Hospital↗
PubMed2001

Restoration of normal ventricular electrophysiology in renovascular hypertensive rabbits after treatment with losartan.

Left ventricular hypertrophy (LVH) is associated with abnormal ventricular electrophysiology. We have shown complete regression of LVH and normalization of ventricular electrophysiology in renovascular hypertensive rabbits treated with captopril. To determine if angiotensin II type 1 receptor (AT1) blockade produces the same benefit, we treated hypertensive rabbits with losartan for 3 months. LVH was evaluated by heart-to-body weight ratio (HW/BW). Vulnerability to ventricular arrhythmia was assessed by ventricular fibrillation threshold (VFT) and dispersion of effective refractory period (ERP). The electrical properties of single left ventricular myocytes were characterized by action potential duration at 90% repolarization (APD90) and inward rectifier K+ current (I(K1)) density. Hypertensive rabbits treated with vehicle (LVH/Vehicle) had higher mean arterial pressure (MAP, 81+/-2 vs. 60+/-2 mm Hg) and HW/BW (2.71+/-0.07 vs. 1.97+/-0.04 g/kg), lower VFT (20+/-1 vs. 39+/-2 mA), larger dispersion of ERP (34+/-3 vs. 14+/-3 ms), longer APD90 (187+/-6 vs. 162+/-6 ms) and lower I(K1) density compared with control rabbits. Hypertensive rabbits treated with losartan (LVH/Losartan) had HW/BW (2.36+/-0.06 g/kg) between those of LVH/Vehicle and control rabbits, whereas MAP (65+/-2 mm Hg), VFT (34+/-2 mA), dispersion of ERP (19+/-1 ms), APD90 (160+/-6 ms), and I(K1) density were significantly different from LVH/Vehicle but similar to control. We conclude that AT1 blockade in renovascular hypertensive rabbits normalizes ventricular electrophysiology.

Action Potentials↗
PubMed2001

Molecular variability of the adhesin-encoding gene pvpA among Mycoplasma gallisepticum strains and its application in diagnosis.

Mycoplasma gallisepticum is an important pathogen of chickens and turkeys that causes considerable economic losses to the poultry industry worldwide. The reemergence of M. gallisepticum outbreaks among poultry, the increased use of live M. gallisepticum vaccines, and the detection of M. gallisepticum in game and free-flying song birds has strengthened the need for molecular diagnostic and strain differentiation tests. Molecular techniques, including restriction fragment length polymorphism of genomic DNA (RFLP) and PCR-based random amplification of polymorphic DNA (RAPD), have already been utilized as powerful tools to detect intraspecies variation. However, certain intrinsic drawbacks constrain the application of these methods. The main goal of this study was to determine the feasibility of using an M. gallisepticum-specific gene encoding a phase-variable putative adhesin protein (PvpA) as the target for molecular typing. This was accomplished using a pvpA PCR-RFLP assay. Size variations among PCR products and nucleotide divergence of the C-terminus-encoding region of the pvpA gene were the basis for strain differentiation. This method can be used for rapid differentiation of vaccine strains from field isolates by amplification directly from clinical samples without the need for isolation by culture. Moreover, molecular epidemiology of M. gallisepticum outbreaks can be performed using RFLP and/or sequence analysis of the pvpA gene.

Adhesins, Bacterial↗
PubMed2001

Gamma interferon can prevent herpes simplex virus type 1 reactivation from latency in sensory neurons.

We recently demonstrated that CD8(+) T cells could block herpes simplex virus type 1 (HSV-1) reactivation from latency in ex vivo trigeminal ganglion (TG) cultures without destroying the infected neurons. Here we establish that CD8(+) T-cell prevention of HSV-1 reactivation from latency is mediated at least in part by gamma interferon (IFN-gamma). We demonstrate that IFN-gamma was produced in ex vivo cultures of dissociated latently infected TG by CD8(+) T cells that were present in the TG at the time of excision. Depletion of CD8(+) T cells or neutralization of IFN-gamma significantly enhanced the rate of HSV-1 reactivation from latency in TG cultures. When TG cultures were treated with acyclovir for 4 days to insure uniform latency, supplementation with recombinant IFN-gamma blocked HSV-1 reactivation in 80% of cultures when endogenous CD8(+) T cells were present and significantly reduced and delayed HSV-1 reactivation when CD8(+) T cells or CD45(+) cells were depleted from the TG cultures. The effectiveness of recombinant IFN-gamma in blocking HSV-1 reactivation was lost when its addition to TG cultures was delayed by more than 24 h after acyclovir removal. We propose that when the intrinsic ability of neurons to inhibit HSV-1 gene expression is compromised, HSV-specific CD8(+) T cells are rapidly mobilized to produce IFN-gamma and perhaps other antiviral cytokines that block the viral replication cycle and maintain the viral genome in a latent state.

Acyclovir↗
PubMed2001

Yellow fever virus encephalitis: properties of the brain-associated T-cell response during virus clearance in normal and gamma interferon-deficient mice and requirement for CD4+ lymphocytes.

Viral encephalitis caused by neuroadapted yellow fever 17D virus (PYF) was studied in parental and gamma interferon (IFN-gamma)-deficient (IFN-gamma knockout [GKO]) C57BL/6 mice. The T-cell responses which enter the brain during acute fatal encephalitis of nonimmunized mice, as well as nonfatal encephalitis of immunized mice, were characterized for relative proportions of CD4+ and CD8+ cells, their proliferative responses, and antigen-specific expression of cytokines during stimulation in vitro. Unimmunized mice accumulated only low levels of T cells within the brain during fatal disease, whereas the brains of immunized mice contained higher levels of both T-cell subsets in response to challenge, with CD8+ cells increased relative to the CD4+ subset. The presence of T cells correlated with the time at which virus was cleared from the central nervous system in both parental and GKO mice. Lymphocytes isolated from the brains of challenged immunized mice failed to proliferate in vitro in response to T-cell mitogens or viral antigens; however, IFN-gamma, interleukin 4 (IL-4), and, to a lesser extent, IL-2 were detectable after stimulation. The levels of IFN-gamma, but not IL-2 or IL-4, were augmented in response to viral antigen, and this specificity was detectable in the CD4+ compartment. When tested for the ability to survive both immunization and challenge with PYF virus, GKO and CD8 knockout mice did not differ from parental mice (80 to 85% survival), although GKO mice exhibited a defect in virus clearance. In contrast, CD4 knockout and Igh-6 mice were unable to resist challenge. The data implicate antibody in conjunction with CD4+ lymphocytes bearing a Th1 phenotype as the critical factors involved in virus clearance in this model.

Animals↗
PubMed2001

Ventricular hypertrophy amplifies transmural repolarization dispersion and induces early afterdepolarization.

The effects of left ventricular hypertrophy (LVH) on the generation of phase 2 early afterdepolarization (EAD) and transmural dispersion of repolarization (TDR) were assessed using arterially perfused rabbit ventricular wedge preparations. Transmembrane action potentials from epicardium, subendocardium, and endocardium were simultaneously recorded together with a transmural ECG. Transmural action potential duration (APD) was also mapped. LVH (renovascular hypertension model) produced significant prolongation in ventricular APD and QT interval. Preferential APD prolongation in subendocardium and endocardium was associated with a marked increase in TDR. Phase 2 EADs were generated from subendocardium or endocardium in all LVH rabbits (15 of 15) in the absence of APD prolonging agents at basic cycle lengths of 2,000-4,000 ms. Phase 2 EAD could produce "R on T" extrasystoles, initiating polymorphic ventricular tachycardia (VT). This study provides the first direct evidence from intracellular recordings that phase 2 EAD could be generated from rabbit intact hypertrophied LV wall in the absence of APD prolonging agents, resulting in R on T extrasystoles capable of initiating polymorphic VT under enhanced TDR.

Action Potentials↗
PubMed2001

Spectrum-analysis and neural networks for imaging to detect and treat prostate cancer.

Conventional B-mode ultrasound currently is the standard means of imaging the prostate for guiding prostate biopsies and planning brachytherapy to treat prostate cancer. Yet B-mode images do not adequately display cancerous lesions of the prostate. Ultrasonic tissue-type imaging based on spectrum analysis of radiofrequency (rf) echo signals has shown promise for overcoming the limitations of B-mode imaging for visualizing prostate tumors. This method of tissue-type imaging utilizes nonlinear classifiers, such as neural networks, to classify tissue based on values of spectral parameter and clinical variables. Two- and three-dimensional images based on these methods demonstrate potential for guiding prostate biopsies and targeting radiotherapy of prostate cancer. Two-dimensional images are being generated in real time in ultrasound scanners used for real-time biopsy guidance and have been incorporated into commercial dosimetry software used for brachytherapy planning. Three-dimensional renderings show promise for depicting locations and volumes of cancer foci for disease evaluation to assist staging and treatment planning, and potentially for registration or fusion with CT images for targeting external-beam radiotherapy.

Biopsy↗
PubMed2001

Multipulse feed strategy for glycerol fed-batch fermentation: a steady-state nonlinear optimization approach.

During glycerol fed-batch fermentation, the process could be divided into multiple equal subintervals, and the feed operation was performed in pulse form at the start of each subinterval. Based on the macrokinetic models, the multipulse feed strategy for both glucose and corn steep slurry was determined by a general nonlinear optimization approach to maximize the final glycerol productivity and still control the residual glucose at a low concentration. The experimental results in a 600-mL Airlift Loop Reactor showed that the tested data with this strategy agreed well with the corresponding model prediction, and that the feed mode with nonlinear optimization could improve the glycerol productivity significantly compared with those determined just by limited experimental optimization in previous studies.

Bioreactors↗
PubMed2001

The influence of task requirements on priming in object decision and matching.

We argue that task requirements can be the determinant in generating different results in studies on visual object recognition. We investigated priming for novel visual objects in three implicit memory tasks. A study-test design was employed in which participants first viewed line drawings of unfamiliar objects and later made different decisions about structural aspects of the objects. Priming for both symmetric and asymmetric possible objects was observed in a task requiring a judgment of structural possibility. However, when the task was changed to one requiring a judgment of structural symmetry, only symmetric possible objects showed priming. Finally, in a matching task in which participants made a same-different judgment, only symmetric possible objects exhibited priming. These results suggest that an understanding of object representation will be most fruitful if it is based on careful analyses of both the task demands and their interaction(s) with encoding and retrieval processes.

Adult↗
PubMed2001

A germline E-cadherin mutation in a family with gastric and colon cancer.

Inactivating mutations have been found in the cell-cell adhesion molecule E-cadherin (CDH1), which acts as a tumor suppressor gene in different kinds of cancers, e.g. primarily diffuse gastric cancer and lobular breast cancer. In this study, we screened for germline alterations in familial gastric and colon cancer cases. In total, 20 gastric and 18 colon cancer patients with both familial gastric and colon cancer were tested for germline E-cadherin alterations by using PCR/SSCP, specific restriction digestion test and sequencing. No pathogenic mutations were identified in the gastric cancer patients. In two colon cancer patients, a missense mutation in exon 12, codon 592 (Ala592Thr) was found. This alteration segregated with diffuse gastric cancer and colon cancer in one of the families. The prevalence of this alteration in the general population and colon cancer cases was almost the same. However, the fact that this alteration (Ala592Thr) segregated with colon cancer and diffuse gastric cancer in one big family, suggests that this E-cadherin missense alteration, beside predisposing to diffuse gastric cancer, also may play a role in colorectal carcinogenesis.

Adult↗
PubMed2001

[The sieving performance of a new polyethersulfone hollow fiber plasma fractionation membrane].

Plasma fractionation membrane is very important in double filtration plasmapheresis. We studied a new polyethersulfone hollow fiber membrane plasma fractionator and evaluated the effect of time, transmembrane pressure (TMP) and mean shear rate on the sieving coefficient (SC) during membrane plasma fractionation. The sieving coefficients of various proteins reached their maximum values at 40 min at the plasma flow rate QI = 30 ml/min and plasma filtrated flow rate QF = 20 ml/min. The QF increased with the increase of TMP, and the point of the intersection of the curve of the QF vs. TMP and the SC vs. TMP was regarded as the ideal condition for plasma fractionation. The plasma filtrated rate PFR = QF/QI = 0.6-0.7. The TMP changed with the change of the mean shear rate, and the mean shear rate had little effect on the SC. The data is of significance to the application of plasma fractionation membrane.

Membranes, Artificial↗
PubMed2001

Kwashiorkor in the United States: fad diets, perceived and true milk allergy, and nutritional ignorance.

BACKGROUND: Kwashiorkor is the edematous form of protein-energy malnutrition. It is associated with extreme poverty in developing countries and with chronic malabsorptive conditions such as cystic fibrosis in developed countries. Rare cases of kwashiorkor in affluent countries unrelated to chronic illness have been reported. We present 12 cases of kwashiorkor unrelated to chronic illness seen over 9 years by pediatric dermatologists throughout the United States, and discuss common causative themes in this easily preventable condition. OBSERVATIONS: Twelve children were diagnosed as having kwashiorkor in 7 tertiary referral centers throughout the United States. The diagnoses were based on the characteristic rash and the overall clinical presentation. The rash consisted of an erosive, crusting, desquamating dermatitis sometimes with classic "pasted-on" scale-the so-called flaky paint sign. Most cases were due to nutritional ignorance, perceived milk intolerance, or food faddism. Half of the cases were the result of a deliberate deviation to a protein-deficient diet because of a perceived intolerance of formula or milk. Financial and social stresses were a factor in only 2 cases, and in both cases social chaos was more of a factor than an absolute lack of financial resources. Misleading dietary histories and the presence of edema masking growth failure obscured the clinical picture in some cases. CONCLUSIONS: Physicians should consider the diagnosis of kwashiorkor in children with perceived milk allergies resulting in frequent dietary manipulations, in children following fad or unorthodox diets, or in children living in homes with significant social chaos. The presence of edema and "flaky paint" dermatitis should prompt a careful dietary investigation.

Diet Fads↗
PubMed2001

Comparison of a 6-hour and 9-hour protocol for evaluation of moderate-to-low risk chest pain patients in an emergency department diagnostic unit.

OBJECTIVE: To compare the 30-day outcomes of patients enrolled in a 6-hour and 9-hour emergency department (ED)-based chest pain centre (CPC) protocol. METHODS: All patients with the chief complaint of chest pain, who were older than 25 years, or with cocaine usage within 96 hours of initial presentation, were eligible for enrolment. Exclusion criteria included acute ST-segment elevation or depression >1 mm in 2 contiguous leads, history of coronary artery disease (CAD), haemodynamic instability or clinical syndromes consistent with unstable angina. Outcomes included ED disposition and cardiac events at 30 days (defined as acute myocardial infarction (AMI), percutaneous trans-luminal coronary angiography (PTCA), coronary artery bypass graft surgery (CABG),ventricular tachycardia or fibrillation (VT/VF) arrest, congestive heart failure (CHF) admission or cardiac-related death). The 9-hour protocol consisted of ST-segment monitoring,serial CK-MB draws at 0, 3,6 and 9 hours as well as a graded exercise test (GXT) prior to ED disposition. The 6-hour protocol eliminated the 9-hour serum marker determination, included cardiac Troponin-I (cTn-I) and allowed a GXT, 3 hours earlier. Follow-up was obtained by medical record review, phone contact, letter and also review of national and state death registries. RESULTS: The 9-hour protocol (October 1991-December 1997) included 2,133 patients and the 6-hour protocol (January 1998- August 1998) had 184 patients enrolled. The 6-hour protocol was not different from the 9-hour one in terms of percentage admissions (9-hour: 310, 14.5%; 6-hour: 33, 17.9%; p=0.213), Coronary Care Unit admission (9-hour: 59, 2.8%; 6-hour: 5, 2.7%; p=0.303) or 30-day cardiac events (9-hour: 38, 1.9%; 6-hour: 2, 1.3%; p=0.605). CONCLUSION: The 6-hour CPC strategy is an effective and safe evaluation method for patients at low to moderate risk for acute coronary syndromes.

Adult↗