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Biomedical subjects

C P Chang

Publications and source records attributed to C P Chang.

At least 19 recordsLinked to original sources
PubMed2006

Heat shock protein 72 overexpression protects against hyperthermia, circulatory shock, and cerebral ischemia during heatstroke.

This study extends our earlier studies in rats by applying our heatstroke model to a new species. Additionally, transgenic mice are used to examine the role of heat shock protein (HSP) 72 in experimental heatstroke. Transgenic mice that were heterozygous for a porcine HSP70i gene ([+]HSP72), transgene-negative littermate controls ([-]HSP72), and normal Institute of Cancer Research strain mice (ICR) under pentobarbital sodium anesthesia were subjected to heat stress (40 degrees C) to induce heatstroke. In [-]HSP72 or ICR, the values for mean arterial pressure, the striatal blood flow, and the striatal PO2 after the onset of heatstroke were significantly lower than those in preheat controls. The core and brain temperatures, the extracellular concentrations of ischemic and injury markers in the striatum, and the striatal neuronal damage scores were significantly greater than those in the preheat controls. In [-]HSP72 or ICR, the body temperatures, cell ischemia content, and injury marker in the striatum were significantly higher, and the mean arterial pressure, striatal blood flow, and striatal PO2 concentration were significantly lower during heatstroke than in [+]HSP72. Accordingly, the latency and the survival times for [+]HSP72 significantly exceeded those of [-]HSP72 or ICR. These results demonstrate that the overexpression of HSP72 in multiple organs improves survival during heatstroke by reducing hyperthermia, circulatory shock, and cerebral ischemia and damage in mice.

Animals↗
PubMed2003

Evaluation of the effects of methylprednisolone pulse therapy in patients with systemic lupus erythematosus with brain involvement by Tc-99m HMPAO brain SPECT.

Methylprednisolone pulse therapy (MPT) was introduced to avoid life-threatening complications in patients with systemic lupus erythematosus (SLE) with brain manifestations; however, the efficacy of MPT in SLE patients with brain involvement is still uncertain and needs to be objectively evaluated. We enrolled 15 female SLE patients with neuropsychiatric manifestations in this study. All patients had normal brain MRI and abnormal brain HMPAO-SPECT findings. Follow-up HMPAO-SPECT studies were conducted 2 weeks after MPT. Serum levels of anticardiolipin antibodies (ACA) and anti-ribosomal P antibodies (anti-P) were measured before and after MPT. Before MPT, 7 patients were positive for ACA and 7 patients were positive for anti-P. After MPT, none of the 15 patients demonstrated positive serologic findings or neuropsychiatric manifestations. Based on the follow up brain HMPAO-SPECT images following MPT, 13 patients showed disappearance of the perfusion defects and 2 patients showed partial recovery of rCBF. Brain HMPAO-SPECT imaging is a logical and objective tool for measuring the effects of MPT in SLE patients with brain involvement by determining of changes in rCBF.

Adult↗
PubMed2002

Abnormal regional cerebral blood flow on 99mTc ECD brain SPECT in patients with primary Sjögren's syndrome and normal findings on brain magnetic resonance imaging.

OBJECTIVE: Technetium-99m ethyl cysteinate dimer (99mTc ECD) single photon emission computed tomography (SPECT) of the brain was used to detect abnormal regional cerebral blood flow (rCBF) in patients with primary Sjögren's syndrome (pSS) and normal findings on brain magnetic resonance imaging (MRI). METHODS: (99m)Tc ECD brain SPECT was performed to detect brain lesions showing hypoperfusion in 32 female patients with pSS and definite neuropsychiatric symptoms or signs. Seventeen female patients with pSS without neuropsychiatric symptoms and signs were included as a control group for comparison. All of the 49 patients with pSS had normal findings on brain MRI. RESULTS: 99mTc ECD brain SPECT showed brain regions with hypoperfusion in 18 (56.3%) of the 32 patients, and parietal lobes were the most common areas with such lesions. By contrast, 99mTc ECD brain SPECT showed brain regions with hypoperfusion in only three (17.6%) of the 17 patients with pSS without neuropsychiatric symptoms or signs. CONCLUSION: This study suggests that 99mTc ECD SPECT is a sensitive tool for detecting regions of hypoperfusion in the brains of patients with pSS and neuropsychiatric symptoms or signs and normal findings on brain MRI. However, a review of the literature showed that the (99m)Tc ECD SPECT findings in patients with pSS were non-specific.

Adult↗
PubMed2001

Molecular analysis of SMN, NAIP and P44 genes of SMA patients and their families.

Mutations of the telomeric survival motor neuron gene (SMN1) are related to spinal muscular atrophy (SMA). However, no phenotype-genotype correlation has been observed since the SMN1 gene is lacking in the majority of patients affected with either the severe form (type I) or the milder forms (types II and III). Here, we analyze the SMN, NAIP and P44 genes in 132 Chinese SMA patients and their families. At least three types of normal allele, and four types of mutant allele were found in this study. The combination of one normal allele with one mutant allele resulted in carriers of different types, and the combination of different mutant alleles accounted for the different genotypes among different types of SMA. Deletions of mutant alleles can be further subgrouped into four types, which includes involving SMN1, SMN1 and NAIP(T) (telomeric portion of NAIP gene), SMN1 and NAIP(T) and P44(T) (telomeric portion of P44 gene), and SMN1 and SMN2 (centromeric portion of SMN gene). Some of the severe (type I) SMA cases correlated with the extent of deletions in the SMN, NAIP and P44 genes or the dosage of SMN gene when both SMN1 and SMN2 are deleted. We also found two novel point mutations, an A insertion at codon 8 (AGT-->AAGT) and an A substitution at codon 228 (TTA-->TAA).

Anterior Horn Cells↗
PubMed2001

Positional importance of Pro53 adjacent to the Arg49-Gly50-Asp51 sequence of rhodostomin in binding to integrin alphaIIbbeta3.

Rhodostomin (RHO), a disintegrin isolated from snake venom, has been demonstrated to inhibit platelet aggregation through interaction with integrin alphaIIbbeta3, but there is a lack of direct evidence for RHO-integrin alphaIIbbeta3 binding. In addition, no study on the length of Arg(49)-Gly(50)-Asp(51) (RGD) loop of RHO influencing on its binding to integrin alphaIIbbeta3 has been reported. In the present study we have developed a highly sensitive dot-blot and glutathione S-transferase-RHO pull-down assays; the latter was coupled with a biotin-avidin-horseradish peroxidase enhanced-chemiluminescence detection system. These were able to demonstrate the direct binding of RHO to integrin alphaIIbbeta3. The pull-down assay further showed that four alanine-insertion mutants upstream of the RGD motif and three insertions downstream of the RGD were able to decrease integrin alphaIIbbeta3 binding activity to only a limited extent. By contrast, two insertions immediately next to RGD and one insertion in front of the Cys(57) caused almost complete loss of binding activity to alphaIIbbeta3. The results of the platelet-aggregation-inhibition assay and platelet-adhesion assay for the insertion mutants were consistent with results of the pull-down assay. It is thus concluded that, although an insertion of a single alanine residue in many positions of the RGD loop has only minor effects on RHO binding to integrin alphaIIbbeta3, the specific position of Pro(53) residue adjacent to the RGD sequence is important for RHO binding to platelet integrin alphaIIbbeta3.

Alanine↗
PubMed2001

A nitric oxide-dopamine link pathway in organum vasculosum laminae terminalis of rat brain exerts control over blood pressure.

1. Experiments were carried out to explore the possible role played by the nitric oxide (NO) and dopamine (DA) system in the organum vasculosum laminae terminalis (OVLT) of rat brain in arterial pressure regulation. 2. Intracerebroventricular (ICV) administration of NO donors such as hydroxylamine or sodium nitroprusside (SNP) caused an up to 59 mmHg decrease in blood pressure (BP) and a decrease in DA release (measured by nafion coated carbon fibre electrodes in combination with voltammetry) in the OVLT. In contrast, ICV administration of N(G)-nitro-L-arginine methyl ester (L-NAME; a constitutive NO synthase inhibitor) or 7-nitroindazol (a neuronal NO synthase inhibitor) caused an up to 98 mmHg increase in BP and an increase in DA release in the OVLT. 3. Intra-OVLT injection of amphetamine (0.1 - 0.3 mg), SKF 38393 (a DA D(1) receptor agonist; 0.01 - 0.03 mg), or apomorphine (a DA D(2,3) receptor agonist; 0.01 - 0.03 mg) caused an increase in BP. On the other hand, intra-OVLT injection of SCH23390 (a DA D(1) receptor antagonist; 0.005 - 0.020 mg) or haloperidol (0.005 - 0.020 mg) caused a decrease in BP. 4. The pressor effects induced by intra-OVLT administration of L-NAME were attenuated by pretreatment with intra-OVLT injection of haloperidol, SCF23390, or 6-hydroxydopamine. In the contrast, the hydroxylamine-, 8-Br-cGMP- or SNP-induced depressor effects were attenuated by pretreatment with intra-OVLT injection of amphetamine, SKF 38393 or apomorphine. 5. The data suggest that activation of a NO-DA link pathway within the OVLT of rat brain exerts control over blood pressure.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2001

Optimal treatment for distal ureteral calculi: extracorporeal shockwave lithotripsy versus ureteroscopy.

BACKGROUND: The optimal treatment for distal ureteral calculi remains controversial. We present data from our institution to compare the efficacy of extracorporeal shockwave lithotripsy (SWL) and ureteroscopy with different lithotripsy modalities (URSL). METHODS: From January 1994 to September 1997, 954 distal ureteral calculi were treated at our institution using in situ SWL (Siemens Lithostar) in 524 patients and ureteroscopy (Wolf 8.0F instrument and Swiss Lithoclast) in 430 patients. Stone sizes and patient ages were similar in these two groups. RESULTS: In the SWL group, the 3-month stone-free rate was 87%, and the effectiveness quotient (EQ) was 68.7%. In the URSL group, there was a 96% stone-free rate with an EQ of 92.1%. The SWL treatment was more expensive than URSL. CONCLUSION: At our institution, ureteroscopy is more efficacious than SWL for the treatment of distal ureteral calculi. In selected patients who had stones >10 mm with evidence of impaction and severe colic pain, we strongly suggest that URSL is the best choice.

Adult↗
PubMed2001

Positive association of ankylosing spondylitis with homozygous HLA-B2704, but protection with B2705 in Taiwan Chinese.

The study was undertaken to determine the effects of HLA-B27 subtypes on susceptibility to ankylosing spondylitis (AS) in Taiwan Chinese, a polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) method was developed for subtyping of HLA-B27. In this series, there are 62 patients with AS who were tested HLA-B27 positive serologically and 738 normal persons over the age of 65. Among the 738 normal controls, 42 (5.7%) were HLA-B27 positive. There were six (14.3%) homozygous for B2704, 18 (42.9%) heterozygous for B2704, 2 (4.8%) double heterozygous for B2704 and B2705, one (2.3%) double heterozygous for B2704 and B2706, 2 (4.8%) homozygous for B2705, 11 (26.1%) heterozygous for B2705, and 2 (4.8%) heterozygous for B2706. In our patients with AS, 37 (59.7%) were homozygous for B2704 and 25 (40.3%) were heterozygous for B2704. The HLA-B27 carrier rate in Taiwan healthy old persons is estimated at 5.7%. Susceptibility to AS is determined by homozygosity for B2704. However, B2705 may be an indicator of protection against AS in Taiwan Chinese.

Aged↗
PubMed2000

Ligand-inducible interaction of the DRIP/TRAP coactivator complex with retinoid receptors in retinoic acid-sensitive and -resistant acute promyelocytic leukemia cells.

Retinoic acid (RA) signaling is mediated by its nuclear receptors RXR and RAR, which bind to their cognate response elements as a heterodimer, RXR/RAR, and act in concert with coregulatory factors to regulate gene transcription on ligand binding. To identify specific cofactors that interact with the RXR/RAR heterodimer in acute promyelocytic leukemia (APL) cells, a double cistronic construct was used that allowed coexpression of the RXR LBD (ligand binding domain) with the RAR LBD as an affinity matrix to pull down interacting proteins from nuclear extracts prepared from a human APL cell line, NB4. A group of proteins was detected whose interaction with RXR/RAR is ligand inducible. The molecular weight pattern of these proteins is similar to that of a complex of proteins previously identified as DRIP or TRAP, which are ligand-dependent transcription activators of VDR and TR, respectively. The RXR/RAR-interacting proteins from NB4 were confirmed to be identical to the DRIP subunits by comparative electrophoresis, Western blot analysis, and in vitro protein interaction assay. In addition to RXR/RAR, the DRIP component can interact directly with the APL-specific PML-RARalpha fusion protein. The same DRIP complex is present in RA-resistant APL cells and in a variety of cancer cell lines, supporting its global role in transcriptional regulation.

Antineoplastic Agents↗
PubMed2000

Analysis of the mRNA transcripts of the survival motor neuron (SMN) gene in the tissue of an SMA fetus and the peripheral blood mononuclear cells of normals, carriers and SMA patients.

Spinal muscular atrophy (SMA) is a disorder characterized by degeneration of the anterior horn cells of the spinal cord. The gene most highly associated with SMA is the survival motor neuron (SMN) gene. In this study, we present an analysis of messenger RNA (mRNA) expression of the SMN gene in peripheral blood mononuclear cells in normal subjects, SMA carriers and patients from 20 SMA families. We found at least 6-8 different transcripts of SMN gene formed by alternative splicing involving exons 3, 5 and 7. We compared transcripts from the different types of SMA and found no definite differences in transcript patterns and amounts. Normal subjects with the telomeric SMN (SMN(T)) gene only had variable splicing resulting in several transcripts, the most dominant being a transcript containing all coding regions. However, SMA patients with the centromeric SMN (SMN(C)) gene only had a higher degree of splice variation and tended to show little or no exon 7. These results demonstrate that SMN(T) and SMN(C) genes participate in alternative splicing phenomena. The different splicing patterns support the view that the SMN(T) gene is responsible for SMA disease. We also analyzed the transcripts from several tissues of an SMA fetus who had a homozygous SMN(T) gene deletion. Different splicing patterns were also found in these tissues, and were similar to the splicing pattern of leukocytes. We compared the major transcripts from exons 4 to 8 of both the SMN(T) and SMN(C) genes and found that the relative proportion varied among normal subjects, SMA carriers and patients. This approach could be used as a novel diagnostic method. We suggest that analyzing the mRNA expression of the SMN gene in peripheral blood mononuclear cells offers an apparently reliable technique for separating SMA patients, carriers, and normal individuals.

Adult↗
PubMed2000

Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in cervical cancer.

OBJECTIVE: PTEN/MMAC1, a candidate tumor suppressor gene located at chromosome 10q23.3, was recently identified and found to be homozygously deleted or mutated in several different types of human tumors. The aim of this study is to determine whether PTEN/MMAC1 is a target for 10q loss of heterozygosity in cervical cancer. METHOD: We examined 50 primary cervical carcinoma specimens using a PCR-based assay followed by SSCP and direct sequencing. The genomic DNA was also confirmed by Southern blot analysis. RESULTS: All specimens except one, which has a 7-base deletion, showed a negative result. Among them, 30 randomly selected cases and their paired noncancerous tissue were further screened using nested RT-PCR. Six of 30 cervical cancerous tissues had aberrant transcripts. However, 4 of the matched noncancerous tissues also had aberrant transcripts. Southern blot analysis of the entire genomic DNA did not reveal any evidence of gene alteration. CONCLUSIONS: Sequence abnormalities in the PTEN/MMAC1 gene were only detected in 1 of 50 cervical cancers analyzed indicating that aberrant PTEN/MMAC1 function is an uncommon event in the development of cervix cancers. However, similar to studies with the TSG101 gene, screening for aberrant transcripts of PTEN/MMAC1 with nested RT-PCR may detect transcripts, which, although they vary from the normal size, may not be related to oncogenesis as they are also frequently found in normal tissues of the same patient.

Adult↗
PubMed2000

The DRIP complex and SRC-1/p160 coactivators share similar nuclear receptor binding determinants but constitute functionally distinct complexes.

Transcriptional activation requires both access to DNA assembled as chromatin and functional contact with components of the basal transcription machinery. Using the hormone-bound vitamin D(3) receptor (VDR) ligand binding domain (LBD) as an affinity matrix, we previously identified a novel multisubunit coactivator complex, DRIP (VDR-interacting proteins), required for transcriptional activation by nuclear receptors and several other transcription factors. In this report, we characterize the nuclear receptor binding features of DRIP205, a key subunit of the DRIP complex, that interacts directly with VDR and thyroid hormone receptor in response to ligand and anchors the other DRIP subunits to the nuclear receptor LBD. In common with other nuclear receptor coactivators, DRIP205 interaction occurs through one of two LXXLL motifs and requires the receptor's AF-2 subdomain. Although the second motif of DRIP205 is required only for VDR binding in vitro, both motifs are used in the context of an retinoid X receptor-VDR heterodimer on DNA and in transactivation in vivo. We demonstrate that both endogenous p160 coactivators and DRIP complexes bind to the VDR LBD from nuclear extracts through similar sequence requirements, but they do so as distinct complexes. Moreover, in contrast to the p160 family of coactivators, the DRIP complex is devoid of any histone acetyltransferase activity. The results demonstrate that different coactivator complexes with distinct functions bind to the same transactivation region of nuclear receptors, suggesting that they are both required for transcription activation by nuclear receptors.

Amino Acid Sequence↗
PubMed2000

Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in hepatocellular carcinoma.

Loss of heterozygosity of chromosome 10q has been reported in hepatoma. Areas with a high rate of loss of genetic material could harbor putative tumor suppressor genes. PTEN/MMAC1, a candidate tumor suppressor gene located at chromosome 10q23.3, has recently been identified and found to be homozygously deleted or mutated in several different types of human tumors. To determine whether the PTEN/MMAC1 gene is a target of 10q loss of heterozygosity in hepatoma, we examined 42 primary hepatomas for mutations in PTEN/MMAC1 by using nested reverse transcriptase polymerase chain reaction (RT-PCR) of the RNA and single-stranded conformation polymorphism (SSCP) analysis of all genomic exons. Although 2 of 42 hepatoma tissues had aberrant transcripts, 5 matched noncancerous liver tissues also had aberrant transcripts. Southern blot analysis of the entire genomic DNA revealed no genomic change. Therefore, like the TSG101 or FHIT gene, aberrant transcripts of PTEN/MMAC1 using the nested RT-PCR method were a common phenomenon for both cancerous and noncancerous liver tissues, which may not be related to oncogenesis. None of the 42 cases had small deletions, point mutations, or insertions. Our results suggest that the PTEN/MMAC1 gene may not play a role in the pathogenesis of hepatoma.

Blotting, Southern↗
PubMed1999

M phase phosphorylation of cytoplasmic dynein intermediate chain and p150(Glued).

To understand how the dramatic cell biological changes of oocyte maturation are brought about, we have begun to identify proteins whose phosphorylation state changes during Xenopus oocyte maturation. Here we have focused on one such protein, p83. We partially purified p83, obtained peptide sequence, and identified it as the intermediate chain of cytoplasmic dynein. During oocyte maturation, dynein intermediate chain became hyperphosphorylated at the time of germinal vesicle breakdown and remained hyperphosphorylated throughout the rest of meiosis and early embryogenesis. p150(Glued), a subunit of dynactin that has been shown to bind to dynein intermediate chain, underwent similar changes in its phosphorylation. Both dynein intermediate chain and p150(Glued) also became hyperphosphorylated during M phase in XTC-2 cells and HeLa cells. Thus, two components of the dynein-dynactin complex undergo coordinated phosphorylation changes at two G2/M transitions (maturation in oocytes and mitosis in cells in culture) but remain constitutively in their M phase forms during early embryogenesis. Dynein intermediate chain and p150(Glued) phosphorylation may positively regulate mitotic processes, such as spindle assembly or orientation, or negatively regulate interphase processes such as minus-end-directed organelle trafficking.

Animals↗
PubMed1999

Oxidation of dichlorvos with hydrogen peroxide using ferrous ion as catalyst.

This study examines how Fenton's reagent (Fe2+ and H2O2) decomposed dichlorvos insecticide. Results showed that dichlorvos decomposed in a two-stage reaction. The first stage is a Fe2+/H2O2 reaction in which dichlorvos swiftly decomposed. In the second stage, dichlorvos decomposed somewhat less rapidly, and it is a Fe3+/H2O2 reaction. The detection of ferrous ions also supports the theory of the two-stage reaction for the dichlorvos oxidation with Fenton's reagent. The dissolved oxygen of the solution decreased rapidly in the first stage reaction, but it slowly increased in the second stage with a zero-order kinetics. The Fenton system decomposed dichlorvos most rapidly when the initial pH in the solution is 3-4. In addition, increasing the concentration of hydrogen peroxide or ferrous ions can enhance the decomposition of dichlorvos. Consequently, the relationship of rate constant (kobs), [H2O2] and [Fe2+] at initial pH 3 is determined as kobs = 2.67 x 10(4)[H2O2]0.7[Fe2+]1.2.

Biodegradation, Environmental↗
PubMed1999

Structure of a HoxB1-Pbx1 heterodimer bound to DNA: role of the hexapeptide and a fourth homeodomain helix in complex formation.

Hox homeodomain proteins are developmental regulators that determine body plan in a variety of organisms. A majority of the vertebrate Hox proteins bind DNA as heterodimers with the Pbx1 homeodomain protein. We report here the 2.35 A structure of a ternary complex containing a human HoxB1-Pbx1 heterodimer bound to DNA. Heterodimer contacts are mediated by the hexapeptide of HoxB1, which binds in a pocket in the Pbx1 protein formed in part by a three-amino acid insertion in the Pbx1 homeodomain. The Pbx1 DNA-binding domain is larger than the canonical homeodomain, containing an additional alpha helix that appears to contribute to binding of the HoxB1 hexapeptide and to stable binding of Pbx1 to DNA. The structure suggests a model for modulation of Hox DNA binding activity by Pbx1 and related proteins.

DNA↗