Biomedical subjects

J W Chang

Publications and source records attributed to J W Chang.

At least 19 recordsLinked to original sources

PubMed2006

Differential gene expression profiling in aggressive bladder transitional cell carcinoma compared to the adjacent microscopically normal urothelium by microdissection-SMART cDNA PCR-SSH.

Identifying novel and known genes that are differentially expressed in aggressive bladder transitional cell carcinoma (BTCC) has important implications in understanding the biology of bladder tumorigenesis and developing new diagnostic and therapeutic agents. In this study we identified the differential gene expression profiles comparing tumor to the adjacent microscopically normal mucosa by manual microdissection on frozen sections. The RNAs extracted from microdissected tissues were amplified by SMART cDNA PCR technology to generate forward subtractive cDNA library by suppressive subtractive hybridization (SSH). We obtained 376 positive clones, one hundred clones of aggressive BTCC subtracted cDNA library were selected at random and inserts were reamplified by PCR. After differential screening by reverse dot blotting, 73 positive clones, that contend inserts putatively upregulated in aggressive BTCC, were further analysed by DNA sequencing, GenBank and EST database searching. Sequencing results showed that 66 clones stand for 23 known genes and 7 clones for three new EST (Genbank number: DN236875, DN236874 and DN236873). In conclusion, microdissection-SMART cDNA PCR-SSH allowed for an efficient way to identify aggressive BTCC-specific differential expressed genes that may potentially be involved in the carcinogenesis and/or progression of aggressive BTCC. These differentially expressed genes may be of potential utility as therapeutic and diagnostic targets for aggressive BTCC.

Carcinoma, Transitional Cell↗

PubMed2006

Prevention of uncuffed hemodialysis catheter-related bacteremia using an antibiotic lock technique: a prospective, randomized clinical trial.

As a result of the high rate of infection, the NKF-K/DOQI guidelines recommended that an uncuffed catheter (UC) should not be used for longer than three weeks. However, the findings of the Dialysis Outcomes and Practice Patterns Study recognized that 48% of new hemodialysis patients in the US and 75% in Europe used UC for temporary access during arteriovenous fistula or graft maturation. The antibiotic lock technique (ALT) has been recommended to prevent catheter-related bacteremia (CRB). Here, we prospectively evaluated the efficacy of catheter-restricted filling using an antibiotic lock solution in preventing CRB. A total of 120 new hemodialysis patients requiring a temporary catheter while waiting for placement and maturation of an arteriovenous fistula or graft were enrolled in this study. Patients with a UC were randomly assigned to receive either an antibiotic-heparin lock solution (antibiotic group: cefazolin 10 mg/ml, gentamicin 5 mg/ml, heparin 1000 U/ml) or a heparin lock solution (no-antibiotic group: heparin 1000 U/ml) as a catheter lock solution during the interdialytic period. The end point of the trial was CRB. CRB developed in seven (11.7%) patients in the no-antibiotic group (Staphylococcus aureus, two; Staphylococcus epidermidis, five) whereas only one patient in the antibiotic group had S. aureus bacteremia. CRB rates per 1000 catheter-days were 0.44 in the antibiotic group versus 3.12 in the no-antibiotic group (P=0.031). Kaplan-Meier analysis also showed that mean CRB-free catheter survival of 59 days (95% CI, 58-61 days) in the antibiotic group was greater than that in the no-antibiotic group (55 days; 95% CI, 50-59 days). The results suggest that ALT may be a beneficial means of reducing the CRB rate in hemodialysis patients with UC.

Adult↗

PubMed2005

Enhanced expression of glutamate decarboxylase 65 improves symptoms of rat parkinsonian models.

In this study, we report the amelioration of parkinsonian symptoms in rat Parkinson's disease (PD) models, as a result of the expression of glutamate decarboxylase (GAD) 65 with a modified cytomegalovirus (CMV) promoter. The transfer of the gene for gamma-amino butryic acid (GAD), the rate-limiting enzyme in gama-amino butrylic acid (GABA) production, has been investigated as a means to increase inhibitory synaptic activity. Electrophysiological evidence suggests that the transfer of the GAD65 gene to the subthalamic nucleus (STN) can change the excitatory output of this nucleus to inhibitory output. Our in vitro results also demonstrated higher GAD65 expression in cells transfected with the JDK promoter, as compared to cells transfected with the CMV promoter. Also, a rat PD model in which recombinant adeno-associated virus-2 (rAAV2)-JDK-GAD65 was delivered into the STN exhibited significant behavioral improvements, as compared to the saline-injected group. Interestingly, we observed that these behavioral improvements were more obvious in rat PD models in which rAAV2-JDK-GAD65 was injected into the STN than in rat PD models in which rAAV2-CMV-GAD65 was injected into the STN. Moreover, according to electrophysiological data, the rAAV2-JDK-GAD65-injected group exhibited more constant improvements in firing rates than did the rAAV2-CMV-GAD65-injected group. These data indicate that the JDK promoter, when coupled with GAD65 expression, is more effective with regard to parkinsonian symptoms than is the CMV promoter.

Adenoviridae↗

PubMed2005

Molecular pathology of low malignant bladder transitional cell carcinoma: a current perspective.

Bladder transitional cell carcinoma (BTCC) actually has two phenotypes: low malignant and aggressive. Most previous molecular and cytogenetic analyses of bladder cancer were focused on aggressive BTCC. Little is known about the events that lead to the development of low malignant BTCC. This review mainly introduces the concept of two types of bladder tumors and then focuses on the molecular pathology of low malignant BTCC in particular. It is hoped that further understanding of the molecular pathology of low malignant BTCC may provide novel therapies and many other clinical benefits in patients with this disease.

Carcinoma, Transitional Cell↗

PubMed2004

Cysticercosis of cerebellopontine cistern: differential diagnosis using MRI.

We report an example of subarachnoid neurocysticercosis located in the left cerebellopontine cistern of a 60 year-old man. The negative results of the serum and cerebrospinal fluid tests for parasites and the unusual MRI findings, such as the uncommon shape, location and extension pattern, made differential diagnosis difficult. Neurocysticercosis was confirmed by surgical and histopathological findings. The clinical and radiographic features of neurocysticercosis are highly variable. In an endemic area, neurocysticercosis should be considered in the differential diagnosis.

Brain Stem↗

PubMed2003

Neurophysiological identification and characterization of thalamic neurons with single unit recording in essential tremor patients.

This study investigated the characteristics of the neuronal activities of the motor thalamus (Vim and Vop) in essential tremor (ET) patients, and compared the results with those of Parkinson's disease (PD) patients. The kinetic (Ki) neurons were found mainly in the Vim, whereas the voluntary (Vo) neurons were found principally in the Vop of ET patients. The mean firing rates of the ET patients were higher than those of the PD patients. In addition, the mean firing rates of the Ki neurons of the ET patients were higher than those of the PD patients in the Vim nuclei. However, the mean firing rates of the ventralis caudalis (Vc) neurons, which respond to sensory stimulation, were similar in each group. An analysis of the incidence of bursting neurons revealed that the Vop nucleus of the ET patients had less bursting neurons than the PD patients. However, in the Vim nucleus, both groups possessed bursting neurons even though the incidence was slightly different. Tremor cells were observed less frequently in the Vim nucleus of ET patients than in the PD patients. This study demonstrated the characteristic features of the neuronal activities of ET patients compared to those of PD patients.

Action Potentials↗

PubMed2003

Effect of subthalamic lesion with kainic acid on the neuronal activities of the basal ganglia of rat parkinsonian models with 6-hydroxydopamine.

The aim of the present study was to investigate the alteration of neuronal activities in the substantia nigra pars reticulata (SNpr) and globus pallidus (GP), after ipsilateral STN lesioning by kainic acid in the rat hemi-parkinsonian 6-hydroxydopamine (6-OHDA) model. In various rat Parkinson's disease (PD) models, an increase in the SNpr firing rate was observed, despite the occurrence of bursting patterns, and subthalamic lesion was found to reduce the mean firing rates and the percentage of bursting neurons in the SNpr. However, the relative proportion of bursting neurons, among all GP neurons, was slightly increased as a result of the subthalamic lesion. The significance of bursting activity in the SNpr and GP remains obscure. Further study is necessary to elucidate the pathophysiological mechanism behind Parkinson's disease.

Action Potentials↗

PubMed2003

Simple bone cyst occurring in calvarium.

A 60 year-old female presented with a non-specific headache that she had experienced for 4 years. A simple skull X-ray indicated a well-defined, lobulated and radiolucent lesion with a thin sclerotic rim involving the parietal bone (Fig. 1A). Computed tomography revealed a hypodense lesion. Magnetic resonance imaging showed a 2 cm-sized cystic lesion in the diploic space with both tabular involvement. This lesion was not enhanced by contrast agent. It was well defined and the periosteum was intact. The cyst paralleled the CSF in signal intensity on all pulse sequences. No fluid levels were detected (Fig. 1B, C, D). After the scalp was incised, a semi-translucent and light yellow- to white-coloured bony lesion was easily identified. The outer bony cortex of this lesion was slightly elevated, and the consistency was same as that of the normal skull. A craniectomy was performed and the cystic skull lesion was removed. The inner surface of this cystic lesion was intact but appeared irregular. The cystic cavity was empty and the dura did not appear to be involved. Histologically, it was a simple cystic cavity without lining epithelium, and the surrounding bony structures were normal (Fig. 1E, F). It was diagnosed as a simple bone cyst (SBC). The postoperative course was uneventful.

Bone Cysts↗

PubMed2003

Anterior cingulotomy for refractory obsessive-compulsive disorder.

OBJECTIVE: This study was designed to prospectively investigate the efficacy and cognitive adverse effects of stereotactic bilateral anterior cingulotomy as a treatment for refractory obsessive-compulsive (OCD) patients for 12 months. METHOD: Patients were eligible if they had severe OCD and rigorous treatments had been unsuccessful. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Clinical Global Impression (CGI) and neuropsychological tests were used to assess the efficacy and cognitive changes of cingulotomy before and 12 months after operation. RESULTS: The mean improvement rate of the Y-BOCS scores achieved from baseline was 36.0%. Out of 14 patients six met responder criteria; 35% or higher improvement rate on Y-BOCS and CGI improvement of very much or much better at 12-month follow-up. There was no significant cognitive dysfunction after cingulotomy. CONCLUSION: Anterior cingulotomy shows few cognitive adverse effects, with about half of the OCD patients demonstrating significant symptomatic improvement.

Adult↗

PubMed2003

Complications after gamma knife radiosurgery for benign meningiomas.

OBJECTIVES: To analyse the results of gamma knife radiosurgery (GKS) for the treatment of intracranial meningiomas and to assess possible factors related to the outcome and complications of such treatment. METHODS: The authors retrospectively reviewed the clinical and radiological data of 179 patients (194 lesions) treated with GKS for meningiomas between May 1992 and October 2000. The mean follow up duration was 37.3 months (range 6.4 to 86.3 months). The study determined the correlation between radiosurgical outcome including imaging changes after GKS and multiple factors such as tumour location and size, patient characteristics, venous sinus status, pre-GKS degree of oedema, other treatment modalities, and radiosurgical parameters. RESULTS: The radiological control rate was 97.1%. Magnetic resonance imaging (MRI) showed complications after GKS in 35 lesions (25.0%) among the 140 lesions followed up with MRI. Complications were divided into peritumorous imaging changes (33 lesions; 23.6%) and transient cranial nerve dysfunction (two lesions; 1.4%). Radiation induced imaging changes were seen mostly in convexity, parasagittal, and falx meningiomas that were deeply embedded in the cortex. About 60% of these were asymptomatic and the overall rate of symptomatic imaging changes was 9.3%. Neurological deficit related to imaging changes developed in only three patients, and all the symptoms were transient. CONCLUSION: GKS for intracranial meningiomas seems to be a safe and effective treatment. However, meningiomas of the convexity, parasagittal region, or falx cerebri have a higher incidence of peritumorous imaging changes after GKS than those of the skull base. Therefore, the use of GKS needs to be considered very cautiously in cerebral hemispheric meningiomas, taking into consideration patient age and general condition, tumour size and location, pattern of cortical embedding, relation between the tumour and venous sinuses, presenting symptoms, and patient preference.

Adolescent↗

PubMed2002

Ictal electrocorticographic findings related with surgical outcomes in nonlesional neocortical epilepsy.

PURPOSE: To characterize ictal electrocorticographic features related to surgical outcomes in nonlesional neocortical epilepsy (NE). METHODS: We analyzed 187 ictal electrocorticograms (ECoG) obtained from 18 patients who had undergone presurgical evaluation and subsequent neocortical resections (frontal: seven, parietal: one, occipital: four, multilobar: six). None of them had any MRI-detectable lesions. Various ECoG data sets recorded from eight patients who achieved a favorable surgical outcome (either seizure free or more than 90% reduction of seizure frequencies) were compared with that from ten patients with unfavorable outcome (less than 90% reduction of seizure frequencies) (follow up duration: 47+/-11 months). RESULTS: Reproducible ictal onset zone (IOZ) in recurrent seizures (P=0.013) and persistent ictal discharges in IOZ from the onset to the end of seizure (P=0.004) were found more frequently in the patients with good outcome. Ictal onset patterns consisting of low voltage fast or high amplitude beta spikes predicted a good surgical outcome while rhythmic sinusoidal activity or rhythmic spike/sharp waves of slow frequency were predictive of poor outcome (P=0.01). The ictal onset rhythm consisting of gamma or beta frequencies was more prevalent in the favorable group (P=0.015). CONCLUSIONS: The presence of stable ictal circuit suggested by the consistent earliest activation of specific electrodes in the repetitive seizures (reproducible IOZ) and the active participation of IOZ throughout the attack were valuable prognostic factors in addition to the morphology and frequency of ictal onset rhythm.

Adolescent↗

PubMed2002

A site-specific mutation of tyrosine hydroxylase reduces feedback inhibition by dopamine in genetically modified cells grafted in parkinsonian rats.

Aromatic L-amino acid decarboxylase (AADC) is necessary for conversion of L-DOPA to dopamine. Therefore, AADC gene therapy has been proposed to enhance pharmacological or gene therapies delivering L-DOPA. However, addition of AADC to the grafts of genetically modified cells expressing tyrosine hydroxylase (TH) and GTP cyclohydrolase 1 (GCH1), which produce L-DOPA in parkinsonian rats, resulted in decreased production of L-DOPA and dopamine owing to feedback inhibition of TH by dopamine. End-product feedback inhibition has been shown to be mediated by the regulatory domain of TH, and site-specific mutation of serine 40 makes TH less susceptible to dopamine inhibition. Therefore, we investigated the efficacy of using TH with serine 40 mutated to leucine (mTH) in an ex vivo gene-therapy paradigm. Primary fibroblasts (PF) from Fischer 344 rats were transduced with retrovirus to express mTH or wild-type rat TH cDNA (wtTH). Both cell types were also transduced with GCH1 to provide the obligate TH cofactor, tetrahydrobiopterin. PF transfected with AADC were used as coculture and cografting partners. TH activities and L-DOPA production in culture were comparable between PFwtTHGC and PFmTHGC cells. In cocultures with PFAADC cells, PFmTHGC cells showed significant reduction in the inhibitory effect of dopamine compared with PFwtTHGC cells. In vivo microdialysis measurement showed that cografting PFAADC cells with PFmTHGC cells resulted in smaller decreases in L-DOPA and no reduction in dopamine levels compared with cografts of PFAADC cells with PFwtTHGC cells, which decreased both L-DOPA and dopamine levels. Maintenance of dopamine levels with lower levels of L-DOPA would result in more focused local delivery of dopamine and less potential side-effects arising from L-DOPA diffusion into other structures. These data support the hypothesis that mutation of serine 40 attenuates TH end-product inhibition in vivo and illustrates the importance of careful consideration of biochemical pathways and interactions between multiple genes in gene therapy.

Amino Acid Substitution↗

PubMed2002

Unilateral globus pallidus internus stimulation improves delayed onset post-traumatic cervical dystonia with an ipsilateral focal basal ganglia lesion.

Treatment with unilateral left globus pallidus internus (GPi) deep brain stimulation is reported in a patient with severe delayed onset post-traumatic cervical dystonia. He had sustained severe head trauma at the age of 17 and had developed a mild right hemiparesis. Three years after the head injury, cervical dystonia with head turning to the left side developed. Magnetic resonance imaging (MRI) showed a discrete GPi lesion on the left side. At the age of 23, he underwent unilateral left GPi deep brain stimulation. He experienced immediate but short lasting benefit from the microlesioning effect of the electrode. With activation of deep brain stimulation, there was significant improvement of the cervical dystonia, persisting for 12 months of follow up. This case underlines the importance of the globus pallidus internus in the generation and amelioration of cervical dystonia.

Adult↗

PubMed2002

The role of inducible nitric oxide synthase in aseptic loosening after total hip arthroplasty.

We collected 16 samples of the membrane which surrounds loose hip prostheses from patients undergoing revision operations for aseptic loosening. To serve as the control group, samples of the synovial tissue and the fibrous capsular tissue were collected from 11 patients undergoing primary hip arthroplasties. Analyses of the expression levels of inducible nitric oxide synthase (iNOS), tumour necrosis factor-alpha (TNF-alpha), and cytosolic phospholipase A2 (cPLA2) mRNAs were performed by a reverse transcription polymerase chain reaction, and the content of nitrite was measured by the Griess reaction using sodium nitrite as the standard. The expression levels of iNOS, TNF-alpha, and cPLA2 mRNAs in the membranes were significantly higher than those in the control samples (p < 0.05). The expression levels of iNOS mRNA and the nitrite content in the membranes significantly correlated with those of TNF-alpha and cPLA2 mRNAs, respectively. In addition, the expression levels of iNOS, TNF-alpha, and cPLA2 mRNAs were significantly higher in membranes from cementless than in those from cemented implants (p < 0.05). Our results suggest that the expression levels of iNOS, TNF-alpha, and cPLA2 mRNAs in the membranes are regulated by closely-related mechanisms and that these have a significant role in aseptic loosening.

Adult↗

PubMed2001

Synthesis of substituted-(l)-tryptophanols from an enantiomerically pure aziridine-2-methanol.

Enantiomerically pure (l)-tryptophanol (5) was synthesized from 4(R)-iodomethyl-2-oxazolidinone (2) and indolylmagnesium bromide in three steps (52% overall yield). Using this procedure, we also prepared various tryptophanols with substituent(s) on the indole ring. Furthermore, optically active 4(R)-iodomethyl-2-oxazolidinone was readily prepared from an enantiomerically pure aziridine-2(S)-methanol in high yield. [reaction: see text]

Journal Article↗

PubMed2001

Augmented expression of peroxiredoxin I in lung cancer.

Comparative proteome analysis was performed between human normal (BEAS 2B) and malignant (A549) lung epithelial cells in an attempt to identify novel biomarkers of lung cancer. Approximately 500 protein spots could be separated by mini two-dimensional electrophoresis and visualized with Coomassie blue R-250. Among those relatively abundant proteins, eight spots were changed more than twofold reproducibly and identified by peptide mass fingerprints using mass spectrometry and database search. The increased proteins in A549 were aldehyde dehydrogenase, peroxiredoxin I, fatty acid binding protein, aldoketoreductase, and destrin, whereas the decreased proteins were galectin-1, transgelin, and stathmin. Since human lung is exposed to continuous oxidative stress, antioxidant enzyme peroxiredoxin I was selected for further investigation and its augmented expression was confirmed in cancer tissues compared to normal tissues from lung cancer patients, suggesting peroxiredoxin I as a potential biomarker of lung cancer.

Amino Acid Sequence↗

PubMed2001

Rudimentary TCR signaling triggers default IL-10 secretion by human Th1 cells.

Understanding the process of inducing T cell activation has been hampered by the complex interactions between APC and inflammatory Th1 cells. To dissociate Ag-specific signaling through the TCR from costimulatory signaling, rTCR ligands (RTL) containing the alpha1 and beta1 domains of HLA-DR2b (DRA*0101:DRB1*1501) covalently linked with either the myelin basic protein peptide 85-99 (RTL303) or CABL-b3a2 (RTL311) peptides were constructed to provide a minimal ligand for peptide-specific TCRs. When incubated with peptide-specific Th1 cell clones in the absence of APC or costimulatory molecules, only the cognate RTL induced partial activation through the TCR. This partial activation included rapid TCR zeta-chain phosphorylation, calcium mobilization, and reduced extracellular signal-related kinase activity, as well as IL-10 production, but not proliferation or other obvious phenotypic changes. On restimulation with APC/peptide, the RTL-pretreated Th1 clones had reduced proliferation and secreted less IFN-gamma; IL-10 production persisted. These findings reveal for the first time the rudimentary signaling pattern delivered by initial engagement of the external TCR interface, which is further supplemented by coactivation molecules. Activation with RTLs provides a novel strategy for generating autoantigen-specific bystander suppression useful for treatment of complex autoimmune diseases.

Calcium Signaling↗

PubMed2001

Design, engineering, and production of human recombinant t cell receptor ligands derived from human leukocyte antigen DR2.

Major histocompatibility complex (MHC) class II molecules are membrane-anchored heterodimers on the surface of antigen-presenting cells that bind the T cell receptor, initiating a cascade of interactions that results in antigen-specific activation of clonal populations of T cells. Susceptibility to multiple sclerosis is associated with certain MHC class II haplotypes, including human leukocyte antigen (HLA) DR2. Two DRB chains, DRB5*0101 and DRB1*1501, are co-expressed in the HLA-DR2 haplotype, resulting in the formation of two functional cell surface heterodimers, HLA-DR2a (DRA*0101, DRB5*0101) and HLA-DR2b (DRA*0101, DRB1*1501). Both isotypes can present an immunodominant peptide of myelin basic protein (MBP-(84-102)) to MBP-specific T cells from multiple sclerosis patients. We have previously demonstrated that the peptide binding/T cell recognition domains of rat MHC class II (alpha1 and beta1 domains) could be expressed as a single exon for structural and functional characterization; Burrows, G. G., Chang, J. W., Bächinger, H.-P., Bourdette, D. N., Wegmann, K. W., Offner, H., and Vandenbark A. A. (1999) Protein Eng. 12, 771-778; Burrows, G. G., Adlard, K. L., Bebo, B. F., Jr., Chang, J. W., Tenditnyy, K., Vandenbark, A. A., and Offner, H. (2000) J. Immunol. 164, 6366-6371). Single-chain human recombinant T cell receptor ligands (RTLs) of approximately 200 amino acid residues derived from HLA-DR2b were designed using the same principles and have been produced in Escherichia coli with and without amino-terminal extensions containing antigenic peptides. Structural characterization using circular dichroism predicted that these molecules retained the antiparallel beta-sheet platform and antiparallel alpha-helices observed in the native HLA-DR2 heterodimer. The proteins exhibited a cooperative two-state thermal unfolding transition, and DR2-derived RTLs with a covalently linked MBP peptide (MBP-(85-99)) showed increased stability to thermal unfolding relative to the empty DR2-derived RTLs. These novel molecules represent a new class of small soluble ligands for modulating the behavior of T cells and provide a platform technology for developing potent and selective human diagnostic and therapeutic agents for treatment of autoimmune disease.

Amino Acid Sequence↗