Biomedical subjects

Y Chang

Publications and source records attributed to Y Chang.

At least 19 recordsLinked to original sources

PubMed2007

Antitumor activity of sorafenib in FLT3-driven leukemic cells.

Activating internal tandem duplication (ITD) insertions in the juxtamembrane domain of the FLT3 tyrosine kinase are found in about one fourth of patients with acute myeloid leukemia and have been shown to be an independent negative prognostic factor for survival. We show that sorafenib (BAY 43-9006, Nexavar) potently inhibits FLT3 enzymatic and signaling activities. In HEK293 cells stably transfected with FLT3-WT or FLT3-ITD, sorafenib blocked basal and ligand dependent FLT3-mediated tyrosine autophosphorylation as well as extracellular signal-regulated kinase1/2 and Stat5 phosphorylation. In leukemia cell lines MV4-11 and EOL-1, sorafenib treatment resulted in decreased cell proliferation and inhibition of FLT3 signaling. The growth of the FLT3-independent RS4-11 cell line was only weakly inhibited by sorafenib. Cell cycle arrest and induction of apoptosis were observed upon treatment with sorafenib in MV4-11 and EOL-1 cells. The antitumor efficacy of sorafenib was evaluated against the MV4-11 leukemia grown subcutaneously in NCr nu/nu mice. Doses of 3 and 10 mg/kg administered orally for 14 days resulted in six and nine out of 10 animals with complete responses, respectively. The demonstration that sorafenib exhibits potent target inhibition and efficacy in FLT3-driven models suggests that this compound may have a therapeutic benefit for patients with FLT3-driven leukemias.

Animals↗

PubMed2006

Methotrexate used in combination with aminolaevulinic acid for photodynamic killing of prostate cancer cells.

Photodynamic therapy (PDT) using 5-aminolaevulinic acid (ALA) to drive production of an intracellular photosensitiser, protoporphyrin IX (PpIX), is a promising cancer treatment. However, ALA-PDT is still suboptimal for thick or refractory tumours. Searching for new approaches, we tested a known inducer of cellular differentiation, methotrexate (MTX), in combination with ALA-PDT in LNCaP cells. Methotrexate alone promoted growth arrest, differentiation, and apoptosis. Methotrexate pretreatment (1 mg l(-1), 72 h) followed by ALA (0.3 mM, 4 h) resulted in a three-fold increase in intracellular PpIX, by biochemical and confocal analyses. After exposure to 512 nm light, killing was significantly enhanced in MTX-preconditioned cells. The reverse order of treatments, ALA-PDT followed by MTX, yielded no enhancement. Methotrexate caused a similar relative increase in PpIX, whether cells were incubated with ALA, methyl-ALA, or hexyl-ALA, arguing against a major effect upon ALA transport. Searching for an effect among porphyrin synthetic enzymes, we found that coproporphyrinogen oxidase (CPO) was increased three-fold by MTX at the mRNA and protein levels. Transfection of LNCaP cells with a CPO-expressing vector stimulated the accumulation of PpIX. Our data suggest that MTX, when used to modulate intracellular production of endogenous PpIX, may provide a new combination PDT approach for certain cancers.

Aminolevulinic Acid↗

PubMed2006

Suitability of human juvenile pancreatic islets for clinical use.

AIMS/HYPOTHESIS: The limited availability of deceased donor pancreases suitable for pancreas and islet transplantation calls for a broader utilisation of donor tissue for transplantation purposes. Young donors, representing, fortunately, a minor but significant pool of individuals, have been largely under-employed, mainly because of anatomical and functional incompatibilities with potential recipients. For islet transplantation, the isolation of pancreatic islets from young donors rarely occurs, because of technical problems. As a result of the peculiar characteristics of young donor pancreases, the standard isolation procedure does not allow efficient separation of the islets from the surrounding exocrine tissue, and favours the generation of mantled islets. Nonetheless, young donor islets offer high qualitative and clinically appealing characteristics. SUBJECTS AND METHODS: We standardised a modified methodology to obtain purified and mantle-free human islets from young donors. This method principally involves efficient delivery of isolation enzyme with reduced mechanical disruption of the pancreas combined with additional filtration steps. RESULTS: We were able to obtain purified and mantle-free human islets from donors as young as 6 months of age with good morphological and functional properties. The good qualitative characteristics of the islets, evidenced in vitro, were proven in vivo, as they were qualitatively superior to islets of older donors in transplantation studies. CONCLUSIONS/INTERPRETATION: This study justifies the utilisation of islets derived from young donors for islet transplantation.

Adolescent↗

PubMed2006

Assessment of hemodynamics properties of a new-type artificial heart valve prosthesis using catheterization and echocardiography.

OBJECTIVE: The objectives of this study were to assess the hemodynamic properties of the newly developed artificial heart valve prosthesis experimentally in laboratory simulation, in an animal model, and clinically in a human model and to compare the results measured by catheterization and echocardiography. METHODS: (1) Laboratory simulation. The prosthesis was tested using a pulsatile flow simulator in the aortic position. Hydrodynamics parameters were automatically analyzed through a custom-designed data processing program. (2) Animal experiment. Six sheep subjected to mitral replacement with 21-mm-valve prosthesis were measured by open cardiac catheterization intraoperatively. Doppler echocardiography and open cardiac catheterization under dobutamine stress were performed in two sheep subjected to implantation 2.5 years ago. (3) Clinical patient observation. Observations were carried out on 14 patients with aortas replacement and 10 patients with bicuspid replacement using both doppler echocardiography and open cardiac catheterization. RESULTS: (1) Laboratory simulation. The results showed that the value of the transvalvular gradient (DeltaP) decreased with the increase of heart rate, and the values were not greater that 10 mm Hg at any given tissue annulus diameter. (2) Animal experiment. The mean DeltaP value of the six sheep was 5.2 +/- 1.7 mm Hg intraoperatively, while the corresponding DeltaP value of the two sheep 2.5 years after implantation was 6.1 +/- 0.3 mm Hg measured by open cardiac catheterization. (3) Clinical patient observation. The mean DeltaP values in the aortic position measured by catheterization and echocardiography were 6.26 approximately 4.10 and 9.42 approximately 7.48 mm Hg, respectively. The gradients in the mitral position were 2.10 approximately 1.9 and 5.28 approximately 4.10 mm Hg, respectively. CONCLUSIONS: The results demonstrate that the new-type bileaflet heart valve prosthesis only generates a relatively low transvalvar gradient and thus has good hemodynamic properties.

Adult↗

PubMed2006

Abdominal obesity, systolic blood pressure, and microalbuminuria in normotensive and euglycemic Korean men.

OBJECTIVES: To evaluate the relationship between abdominal obesity and microalbuminuria (MA) in normotensive, euglycemic Korean men. DESIGN: A cross-sectional study at a health screening center. SUBJECTS: A total of 1321 healthy, normotensive Korean men, aged 20-78 years, with a fasting plasma glucose level <100 mg/dl. MEASUREMENTS: Height, weight, and waist; systolic blood pressure (SBP); diastolic blood pressures (DBP); urinary albumin to creatinine ratio (ACR); fasting glucose, insulin, lipids, C-reactive protein (CRP), and white blood cell count. Waist circumference (WC) was used to indicate abdominal obesity and a single measurement of ACR was used to estimate MA. We also calculated body mass index (BMI) based on weight and height. RESULTS: Mean BMI, WC, and SBP were significantly higher in subjects with MA than in those without (24.8+/-4.1 vs 23.8+/-2.7 kg/m2, 86+/-9 vs 83+/-8 cm, and 115+/-5 vs 112+/-7 mmHg, respectively). Multiple logistic regression analyses showed that only WC and SBP were independent predictors of MA. CONCLUSION: WC and SBP were positively associated with MA in normotensive and euglycemic Korean men.

Abdominal Fat↗

PubMed2006

Clinical and magnetic resonance imaging features of nasopharyngeal lymphoma in two cats with concurrent intracranial mass.

Lymphoma is reported to be the most common nasal and second most common intracranial neoplasm in cats. Intracranial lymphoma may occur as a primary central nervous system lymphoma or as part of multi-centric disease. Two cats were presented with histopathologically confirmed nasopharyngeal lymphoma and concurrent mass within the middle fossa of the cranial cavity, with magnetic resonance imaging suggestive of direct communication. Both cats demonstrated evidence of bilateral oculomotor nerve deficits and upper respiratory tract noise. In one cat, bilateral optic nerve deficits were also present. The magnetic resonance imaging features were similar in both cases and demonstrated a contrast-enhancing intracranial mass on the ventral aspect of the middle fossa of the cranial cavity and an adjacent mass arising from the dorsal aspect of the nasopharynx. Lymphoma should be included as an important differential diagnosis in cats presented with middle cranial fossa syndrome (in particular ophthalmoplegia) and stertor.

Animals↗

PubMed2006

Idiopathic epilepsy in dogs: owners' perspectives on management with phenobarbitone and/or potassium bromide.

OBJECTIVES: To explore seizure management from the perspective of the owners of dogs with idiopathic epilepsy. METHODS: Questionnaires were mailed to owners of 29 dogs under management for suspected or diagnosed idiopathic epilepsy through the clinics of the Small Animal Hospital of the University of Glasgow Veterinary School, using either phenobarbitone or potassium bromide alone or in combination. RESULTS: The postal survey had an 86 per cent response rate. Analysis of the responses demonstrated that "the dog's quality of life", "adequate seizure frequency" and "acceptable side effects of antiepileptic drugs" were the three greatest concerns for owners; 52 per cent of owners strongly agreed that the seizure management for their dog was adequate, though the seizure frequency reported varied within this group; the majority of owners did not consider the administration of medication a nuisance. However, approximately 60 per cent of owners reported that caring for an epileptic dog had an effect on the organisation of their free time, though this was not dependent on perception of seizure control. Opinions as to the value of further diagnostic procedures, in particular intracranial imaging, were significantly affected by having pet health insurance. CLINICAL SIGNIFICANCE: From the owners' perspective, adequacy of seizure control is determined by the balance between "the dog's quality of life", "adequate seizure frequency" and "acceptable side effects of antiepileptic drugs". A frequency of less than one seizure every three months is associated with the perception by owners of adequate seizure control.

Animals↗

PubMed2006

Viewing the functional consequences of traumatic brain injury by using brain SPECT.

High-resolution brain SPECT is increasingly benefiting from improved image processing software and multiple complementary display capabilities. This enables detailed functional mapping of the disturbances in relative perfusion occurring after TBI. The patient population consisted of 26 cases (ages 8-61 years)between 3 months and 6 years after traumatic brain injury.A very strong case can be made for the routine use of Brain SPECT in TBI. Indeed it can provide a detailed evaluation of multiple functional consequences after TBI and is thus capable of supplementing the clinical evaluation and tailoring the therapeutic strategies needed. In so doing it also provides significant additional information beyond that available from MRI/CT. The critical factor for Brain SPECT's clinical relevance is a carefully designed technical protocol, including displays which should enable a comprehensive description of the patterns found, in a user friendly mode.

Adolescent↗

PubMed2005

Structure and properties of phospholipid-peptide monolayers containing monomeric SP-B(1-25) I. Phases and morphology by epifluorescence microscopy.

Epifluorescence microscopy was used to study the structure and phase behavior of phospholipid films containing a human-sequence monomeric SP-B(1-25) synthetic peptide (mSP-B(1-25)). Measurements were done directly at the air-water (A/W) interface on films in a Langmuir-Whilhelmy balance coupled to a fluorescence microscope and real-time detection system to yield an approximate optical resolution of 1 mum. Fluorescence was achieved by laser excitation of 2-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoyl)-1-hexadecanoyl-sn-glycero-3-PC (BODIPY-PC, concentration </=1 mol%). The presence of mSP-B(1-25) in films of 4:1 (mol/mol) 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (sodium salt) (DOPG) had a substantial effect on lipid morphology and phase behavior that depended on both surface pressure and peptide concentration (10, 5, and 1 wt.%). The mSP-B(1-25) peptide tended to fluidize phospholipid monolayers based on expanded molecular areas and reduced collapse pressures. In addition, epifluorescence measurements revealed the formation of solid-phase domains apparent as three-armed counterclockwise spirals separated from regions of fluid liquid-expanded phase domains in compressed phospholipid-peptide films. The appearance of these separated solid-phase domains resembled pure L-DPPC rather than the ensemble-type solid domains found in films of DPPC/DOPG alone and were most apparent when 10 wt.% mSP-B(1-25) was present. In contrast, films containing lower, more physiological mSP-B(1-25) contents of 5 and 1 wt.% exhibited a prominent intermediate 'dendritic' phase that increased in extent as surface pressure was raised. This phase was characterized by branching structures that formed a lattice-like mesh network with fluorescence intensities between a dye-depleted solid domain and a dye-enriched liquid phase. These results indicate that mSP-B(1-25) at near-physiological levels produces morphological changes in phospholipid monolayers analogous to those observed for native SP-B(1-79).

Air↗

PubMed2005

Structure and properties of phospholipid-peptide monolayers containing monomeric SP-B(1-25) II. Peptide conformation by infrared spectroscopy.

The conformation and orientation of synthetic monomeric human sequence SP-B(1-25) (mSP-B(1-25)) was studied in films with phospholipids at the air-water (A/W) interface by polarization modulation infrared reflectance absorption spectroscopy (PM-IRRAS). Modified two-dimensional infrared (2D IR) correlation analysis was applied to PM-IRRAS spectra to define changes in the secondary structure and rates of reorientation of mSP-B(1-25) in the monolayer during compression. PM-IRRAS spectra and 2D IR correlation analysis showed that, in pure films, mSP-B(1-25) had a major alpha-helical conformation plus regions of beta-sheet structure. These alpha-helical regions reoriented later during film compression than beta structural regions, and became oriented normal to the A/W interface as surface pressure increased. In mixed films with 4:1 mol:mol acyl chain perdeuterated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (sodium salt) (DPPC-d(62):DOPG), the IR spectra of mSP-B(1-25) showed that a significant, concentration-dependent conformational change occurred when mSP-B(1-25) was incorporated into a DPPC-d(62):DOPG monolayer. At an mSP-B(1-25) concentration of 10 wt.%, the peptide assumed a predominantly beta-sheet conformation with no contribution from alpha-helical structures. At lower, more physiological peptide concentrations, 2D IR correlation analysis showed that the propensity of mSP-B(1-25) to form alpha-helical structures was increased. In phospholipid films containing 5 wt.% mSP-B(1-25), a substantial alpha-helical peptide structural component was observed, but regions of alpha and beta structure reoriented together rather than independently during compression. In films containing 1 wt.% mSP-B(1-25), peptide conformation was predominantly alpha-helical and the helical regions reoriented later during compression than the remaining beta structural components. The increased alpha-helical structure of mSP-B(1-25) demonstrated here by PM-IRRAS and 2D IR correlation analysis in monolayers of 4:1 DPPC:DOPG containing 1 wt.% (and, to a lesser extent, 5 wt.%) peptide may be relevant for the formation of the intermediate order 'dendritic' surface phase observed in similar surface films by epi-fluorescence.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2005

DNA vaccination with an insulin construct and a chimeric protein binding to both CTLA4 and CD40 ameliorates type 1 diabetes in NOD mice.

Type 1 diabetes (T1D), a T-cell-mediated autoimmune disease, could be attributed to many defects in nonobese diabetic (NOD) mice, including deficient expressions of costimulatory molecules that impair antigen presentation. Thus, this deficient antigen presentation may result in a reduced ability to induce a tolerogenic response through negative selection/regulation of autoreactive T cells. Improperly activated T cells seem to be able to induce autoimmune responses causing diabetes. To re-establish tolerance to autoantigens by modulating costimulation, we constructed and tested a new type of DNA vaccine encoding a membrane-bound preproinsulin (mbPPI) and a chimeric gene vector encoding mutant B7.1/CD40L (mB7.1/CD40L) fusion protein. This mutant B7.1 binds CTLA4 but not CD28. We report that young NOD mice immunized with mbPPI along with mB7.1/CD40L DNA vectors significantly reduced diabetes incidence while treatment with CTLA4/IgG1 exacerbated diabetes. In conclusion, the combination of mbPPI and mB7.1/CD40L was able to protect against autoimmunity and diabetes in NOD mice possibly by promoting a more efficient presentation of autoantigen PPI and inducing specific tolerance to PPI by negatively regulating autoreactive T cells.

Animals↗

PubMed2005

Characterization of a novel allele HLA-B*3549.

A novel HLA-B allele, B*3549, was identified in a bone marrow transplantation candidate. B*3549 differs from B*3525 by two nucleotides at exon 2, position 142 (T to G) and 165 (G to C). The difference at position 142 resulted in an amino acid difference (serine to alanine). However, the difference at position 165 did not cause any amino acid change. This novel allele was found on a haplotype with A*3101, B*3549, Cw*0401, DRB1*0407, and DQB1*0302.

Alleles↗

PubMed2004

Replacement of recipient stromal/mesenchymal cells after bone marrow transplantation using bone fragments and cultured osteoblast-like cells.

Abstract We present our experience on treatment of three children with potentially fatal diseases using a unique protocol for non-myeloablative bone marrow transplantation. The protocol was designed to promote engraftment of bone marrow stromal/mesenchymal cells (SC/MSCs) based on the knowledge from preclinical models over the last three decades. Accordingly, our protocol is the first to test the use of bone fragments as an ideal vehicle to transplant such cells residing in the bone core. Because of the paucity of knowledge for optimum transplantation of SC/MSCs in humans, we used a multifaceted approach and implanted bone fragments both intraperitoneally and directly into bone on day 0 of BMT. We also infused cultured donor osteoblast-like cells intravenously post-BMT. We were able to achieve high levels of stroma cell engraftment as defined by molecular analyses of bone biopsy specimens.

Bone Marrow Transplantation↗

PubMed2004

Prolongation of islet allograft survival following ex vivo transduction with adenovirus encoding a soluble type 1 TNF receptor-Ig fusion decoy.

Islet transplantation is a viable long-term therapeutic alternative to daily insulin replacement for type I diabetes. The allogeneic nature of the transplants poses immunological challenges for routine clinical utility. Gene transfer of immunoregulatory molecules and those that improve insulin release kinetics provides rational approaches to facilitate allogeneic islet transplantation as a potential therapy. We have examined the efficacy of a soluble type 1 tumor necrosis factor receptor (TNFR) immunoglobulin-Fc fusion transgene (TNFR-Ig) to protect human islets from cytokine-induced apoptosis in culture, as well as in facilitating allogeneic islet transplants in diabetic mice. Cultured human islets were transduced with an adenoviral vector encoding human TNFR-Ig (Ad-TNFR-Ig). TNFR-Ig protein was secreted by cultured islets, as well as by transduced mouse islet transplants recovered from mouse recipients. Glucose-induced insulin release kinetics were comparable among untransduced, Ad-TNFR-Ig-infected human islets and vector-transduced islets exposed to cytokines. In parallel, Ad-TNFR-Ig-infected islets were protected from cytokine-induced apoptosis activation. Finally, diabetic mice transplanted with allogeneic islets expressing TNFR-Ig returned to and maintained normoglycemia significantly longer than untransduced islet recipients. These data support the potential utility of TNFR-Ig gene transfer to islets as a means of facilitating allogeneic islet transplantation.

Adenoviridae↗

PubMed2004

Cardiac complications of enterovirus rhombencephalitis.

BACKGROUND: Epidemics of enterovirus 71 infection have caused the death of many children throughout the world. Rhombencephalitis, brain stem encephalitis, and heart failure were present in all of the fatal cases. However, no evidence of myocarditis was noted in the heart specimens, and the mechanism of heart failure remains unknown. AIMS: To characterise the presentation of cardiac complications in children with enterovirus rhombencephalitis and discuss its pathogenesis. METHODS: Ninety one consecutive patients with enterovirus rhombencephalitis underwent echocardiography. Of these, 17 patients (nine male, eight female; median age 14 months, range 4-57 months) with left ventricular dysfunction were studied. RESULTS: Tachycardia was noted in all patients and systemic hypertension in 12. Muscle-brain fraction of creatine kinase was >5% in 14 patients. Plasma norepinephrine and epinephrine levels were significantly raised in the three patients in whom these were analysed. Electrocardiographic abnormalities were noted in eight patients. Pulmonary oedema was complicated in 15 patients. The initial ejection fraction of the left ventricle was 22-58% (mean 37%, SD 11%). All patients deteriorated to hypotensive shock within 12 hours and 13 died. Heart specimens from seven patients showed no evidence of myocarditis, but significant coagulative myocytolysis, myofibrillar degeneration, and cardiomyocyte apoptosis were observed. CONCLUSIONS: Acute heart failure was noted in 19% of patients with enterovirus rhombencephalitis, which had a fatality rate of 77%. It was not caused by myocarditis but possibly by neurogenic cardiac damage.

Blood Pressure↗

PubMed2003

MSTAR: a submicrometer absolute metrology system.

The Modulation Sideband Technology for Absolute Ranging (MSTAR) sensor permits absolute distance measurement with subnanometer accuracy, an improvement of 4 orders of magnitude over current techniques. The system uses fast phase modulators to resolve the integer cycle ambiguity of standard interferometers. The concept is described and demonstrated over target distances up to 1 m. The design can be extended to kilometer-scale separations.

Journal Article↗

PubMed2003

High frequency plant regeneration from immature embryos of an elite barley cultivar (Hordeum vulgare L. cv. Morex).

An efficient plant regeneration system was developed for Hordeum vulgare L. 'Morex' barley, an important United States malting cultivar. The protocol was based on a series of experiments involving the sizes of immature embryos and the culture media. We found that the embryo size is critical for the establishment of embryogenic callus. Smaller embryos (0.5-1.5 mm) showed a much higher ability to produce embryogenic callus capable of regenerating green plants with fewer albinos than did the larger embryos (1.6-3.0 mm). Either 3 mg/l 2,4-dichlorophenoxyacetic acid or dicamba in modified Murashige and Skoog's (MS) medium was optimum for the induction of embryogenic callus. The embryogenic callus maintained high regeneration during six subcultures in the callus induction medium. Efficient shoot regeneration was obtained on modified MS medium containing 0.5-1.0 mg/l 6-benzylaminopurine (BA). Regenerated shoots were rooted on half-strength MS medium containing 0.2 mg/l IBA. Plants were successfully transferred to soil and grown to maturity in the greenhouse. This efficient plant regeneration system provides a foundation for generating transgenic plants of this important barley cultivar.

2,4-Dichlorophenoxyacetic Acid↗

PubMed2002

Pharmacodynamics of mivacurium chloride in 13- to 18-yr-old adolescents with thermal injury.

BACKGROUND: Burned patients demonstrate resistance to the effects of non-depolarizing blocking drugs as a result of acetylcholine receptor changes. They also have decreased activity of plasma cholinesterase (PCHE), which metabolizes mivacurium. We hypothesized that decreased PCHE activity would decrease metabolism of mivacurium, and counteract the receptor-related resistance following burns. METHODS: Thirteen burned patients and six controls, aged 13-18 yr were followed in 27 studies. The burned patients were sub-classified as having 10-30% or >30% body surface area burn and were studied whenever possible at < or =6 days, and at 1-12 weeks after the burn. Mivacurium pharmacodynamics were examined following a bolus (0.15 mg kg(-1)) dose, and during and after a continuous infusion. RESULTS: Following a bolus, the onset time and the maximal effect were similar to controls. Recovery was prolonged in the 10-30% burn group at 1-12 weeks (P<0.008), with a similar trend in the >30% burn group at < or =6 days (P<0.082) compared with controls. The infusion requirements for mivacurium were not increased in the burned groups. The PCHE activity was decreased in all burn groups and was inversely related to recovery following the bolus (r=0.73, P<0.001) and the infusion (r=0.69, P<0.001). CONCLUSION: In contrast to previous studies with non-depolarizers in burned patients, normal mivacurium doses can produce paralysis, at least as rapidly as in controls, but with a possibility of a prolonged recovery from block. The standard dose of mivacurium in the presence of decreased PCHE activity is in effect, a relative overdose that explains the above findings. Mivacurium is an effective drug for use in burns, irrespective of time after, or magnitude of burn injury.

Adolescent↗