Biomedical subjects

C K Chang

Publications and source records attributed to C K Chang.

At least 73 records · Page 4Linked to original sources

PubMed1997

Secular trend and age-period-cohort analysis of prostate cancer mortality in Taiwan.

PURPOSE: We evaluated the secular mortality trend of prostate cancer in Taiwan from 1964 through 1994. MATERIALS AND METHODS: Analyses were based on vital statistics. Relative risks associated with each of the age, period and cohort effects on secular mortality were estimated from a log-linear Poisson model. RESULTS: Age adjusted mortality rates increased more than 2-fold during the last 30 years in Taiwan. Age-period-cohort analysis showed that the age effect was the strongest. CONCLUSIONS: Factors related to aging are the main reason for the increase in prostate cancer mortality in Taiwan during the least 3 decades.

Adult↗

PubMed1997

The role of subcellular localization in initiation of apoptosis by photodynamic therapy.

Rapid initiation of apoptosis can be induced by photodynamic therapy, depending on the cell line and sensitizer employed. In this study, we evaluated the photodynamic responses to two structurally related photosensitizing agents, using the P388 murine leukemia cell line in culture. Photodamage mediated by tin etiopurpurin involved lysosomes and mitochondria and yielded a rapid apoptotic response; apoptotic nuclei were observed within 60 min after PDT. A drug analog, tin octaethylpurpurin amidine, targeted lysosomes, mitochondria and cell membranes; apoptotic nuclei were not observed until 24 h after PDT. These results, together with other recent reports, are consistent with the hypothesis that membrane photodamage can delay or prevent an apoptotic response to PDT.

Animals↗

PubMed1996

Lack of association of the apoE4 allele with hippocampal sclerosis dementia.

We determined the apolipoprotein E4 (apoE) genotype in 12 cases of autopsy-confirmed hippocampal sclerosis dementia (HSD), a disorder characterized pathologically by neuronal degeneration, predominantly of temporal lobe structures, without senile plaques or neurofibrillary tangles. The frequency of the apoE4 allele in HSD was 12.5%, similar to that of a control population and significantly different from the approximately 40% found in Alzheimer's disease (AD) (P < 0.001). These observations suggest that apoE4 is not a risk factor for HSD.

Aged↗

PubMed1996

Efficacy of anti-tumor necrosis factor polyclonal antibody on phosphoenolpyruvate carboxykinase expression in septic and endotoxemic rats.

We studied the protective effect of anti-tumor necrosis factor-alpha (anti-TNF) polyclonal antibody on phosphoenolpyruvate carboxykinase (PEPCK) expression in lipopolysaccharide-induced endotoxemia and peritonitis sepsis induced by cecal incision. At 3 h after intraperitoneal lipopolysaccharide injection, levels of serum glucose, liver glycogen, and PEPCK expression were decreased and serum TNF was elevated. In contrast, 3 h after cecal incision, levels of serum glucose, serum TNF, and PEPCK expression were elevated. At 6 h after cecal incision (terminal sepsis), serum TNF remained elevated and levels of serum glucose, liver glycogen, and PEPCK expression were decreased. Circulating TNF was not detected in septic and endotoxemic rats pretreated with anti-TNF. Passive immunization with rat anti-TNF antibody restored PEPCK expression in early endotoxemia and sepsis (3 h), but not in terminal sepsis (6 h). Anti-TNF failed to reverse sepsis-induced hypoglycemia and hyperglycemia, suggesting that besides TNF, some other mediators are involved in glucose dyshomeostasis.

Animals↗

PubMed1996

Rapid initiation of apoptosis by photodynamic therapy.

Photodynamic therapy (PDT) of neoplastic cell lines is sometimes associated with the rapid initiation of apoptosis, a mode of cell death that results in a distinct pattern of cellular and DNA fragmentation. The apoptotic response appears to be a function of both the sensitizer and the cell line. In this study, we examined photodynamic effects of several photosensitizers on murine leukemia P388 cells. Two drugs, a porphycene dimer (PcD) and tin etiopurpurin (SnET2), which localized at lysosomal sites, were tested at PDT doses that resulted in 50% loss of viability (LD50), measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. An oligonucleosomal pattern of DNA degradation was observed within 1 h after irradiation. Neither sensitizer antagonized PDT-mediated internucleosomal DNA cleavage by the other. Very high PDT doses with either agent abolished this rapid internucleosomal cleavage. Exposure of cells to high concentrations of either sensitizer in the dark also resulted in rapid DNA fragmentation to nucleosomes and nucleosome multimers; this effect was not altered by the antioxidant 6-hydroxy-2,5,7,8-tetramethyl-chroman-2-carboxylic acid (trolox), although the latter could protect cells from cytotoxicity and apoptotic effects caused by LD50 PDT doses. Photodamage from two cationic sensitizers, which localized at membrane sites, caused rapid DNA cleavage to 50 kb particles; however, no further fragmentation was detected after 1 h under LD10, LD50 or LD95 PDT conditions. Moreover, the presence of either cationic sensitizer inhibited the rapid internucleosomal cleavage induced by SnET2 or PcD photodamage. The site of photodynamic action may therefore be a major determinant of the initiation and rate of progression of apoptosis.

Animals↗

PubMed1996

Neuroendocrine cell-axonal complexes in the minor vestibular gland.

OBJECTIVE: To study neuroendocrine cells and nerves in vestibular glands of patients with vestibulitis. STUDY DESIGN: Substance P chromogranin, serotonin and neuron-specific enolase immunoreactivity was studied in vestibular gland tissue. Electron microscopic analysis was performed on vestibular duct tissue. RESULTS: Neuroendocrine cells containing immunoreactive serotonin and chromogranin were demonstrated in a vestibular gland duct of a patient with vestibulitis. Substance P immunoreactive axons were found in submucosal nerves, and rare, positively staining axons were seen in the duct epithelium. In another patient neuroendocrine cells with closely applied intraepithelial axons were demonstrated by electron microscopy in the duct of a vestibular gland. CONCLUSION: Intraepithelial axons are present in ducts of vestibular glands, where they are closely applied to serotonin-containing neuroendocrine cells. This close association and the presence of substance P immunoreactivity in local nerves may play a role in the symptomatology of vestibulitis.

Adult↗

PubMed1995

Sites of photodamage in vivo and in vitro by a cationic porphyrin.

Localization and photodynamic efficacy of a monocationic porphyrin (MCP) were assessed using murine leukemia cells in culture. This sensitizer localized at surface membrane loci and catalyzed selective photodamage to membrane structures. Although both cationic and hydrophobic, this porphyrin was not recognized by the multidrug transporter, which excludes many cationic agents from cells that express multidrug resistance. Photodynamic studies with the murine radiation-induced fibrosarcoma tumor model indicated moderate photosensitization of neoplastic lesions in vivo at 3 h, but not at 24 h after sensitizer administration. Pharmacokinetic studies indicate that plasma levels, not tissue levels were the major determinant of photodynamic therapy (PDT) response. Consistent with this observation, vascular damage and disturbances of tissue perfusion followed PDT. These effects were more pronounced in tumor-bearing skin than in normal skin. The therapeutic response to MCP appeared to be related mainly to secondary, probably vascular, effects.

Animals↗

PubMed1994

trans-activation of the HIV promoter by a cDNA and its genomic clones of human herpesvirus-6.

Human herpesvirus 6 (HHV-6) is a lymphotropic herpesvirus, and in vitro, it can productively infect human CD4+ T cells as HIV-1. Co-infection of T cells by HIV-1 and HHV-6 can lead to both activation of the HIV-1 promoter and acceleration of the cytopathic effects. An HHV-6 (GS) cDNA clone, pCD41, encoding for a 41-kDa nuclear protein was identified and characterized previously (Chang and Balachandran, J. Virol. 65, 2884-2894 and 7085, 1991). Sequence analyses show that this protein has significant homology with the human cytomegalovirus UL44 gene coding for the ICP36 family of early-late-class phosphoprotein. Using this cDNA as the probe, a 3.8-kb EcoRI genomic fragment encoding the HHV-6(GS)P41 was cloned and designated as pGD41. When cotransfected with the HIV LTR CAT into CV-1 cells, both the pCD41 and pGD41 clones trans-activated the HIV LTR. Sequence analyses of pCD41 indicate that there are two potential open reading frames (ORFs), A and B, which are homologous to the ORFs found in the genomic clone pGD41. Deletion constructs of the pCD41 clone demonstrated that ORF-A was critical for the HIV LTR activation. Deletion analyses of the pCD41 ORF-A and the use of promoter constructs further mapped an internal functional promoter within the pCD41 sequence that can direct the synthesis of the trans-activating protein. By using HIV LTR deletion mutants, the NF-kappa B binding sites were found to be critical for response to the pCD41 trans-activation.

Amino Acid Sequence↗

PubMed1994

Biodistribution and PDT efficacy of a ketochlorin photosensitizer as a function of the delivery vehicle.

C8KC is a new ketochlorin photosensitizer that must be formulated with an emulsifier because of its poor water solubility. In this report, we compare properties of Cremophor EL (CRM) and Tween 80 as delivery vehicles for C8KC. Unlike Tween 80, CRM altered the physical properties of both human and mouse plasma lipoproteins, resulting in decreased electrophoretic mobility of the individual lipoproteins along with the formation of a lipoprotein degradation product: a phospholipid fraction of low buoyant density. In human plasma, where there was sufficient low-density lipoprotein (LDL) for a distinction to be made, CRM caused a shift in binding of a ketochlorin from albumin to LDL and the degraded lipoprotein fraction. In mice bearing the RIF tumor, the use of CRM for drug formulation was associated with longer plasma and tissue persistence of C8KC, and enhanced photodynamic therapy (PDT) efficacy. These results indicate the importance of both sensitizer and vehicle as determinants of PDT efficacy.

Animals↗

PubMed1994

Haem d1 and other haem cofactors from bacteria.

Several bacterial haem prosthetic groups whose structures deviate significantly from the ubiquitous protohaem (Fe-protoporphyrin) have been discovered recently. These newly discovered pigments contain dramatic modifications in their aromatic core and/or side chains. Examples include the dioxoisobacteriochlorin-type haem d1 and the chlorin-type haem d as well as the haem a-like haem o. Total syntheses of these macrocycles have been accomplished. Synthetic haem d1 and its analogues were used in reconstitution studies with nitrite reductase which revealed the importance of the oxo groups and the acrylate side chain for enzymic activity. The structural features of these porphyrinoids immediately suggest some possible, but as yet unproven, biosynthetic pathways.

Crystallography, X-Ray↗

PubMed1993

Photosensitization with methylene-linked porphyrin dimers.

The photodynamic therapy (PDT) efficacy of a series of porphyrin dimers linked by methylene groups was evaluated using the radiation-induced fibrosarcoma (RIF) tumor model. Longer chain length led to greater efficacy and increased dimer hydrophobicity. This result was correlated with the persistence of porphyrins in plasma, but not with tissue levels.

Animals↗

PubMed1993

Identification and mapping of the gene encoding the glycoprotein complex gp82-gp105 of human herpesvirus 6 and mapping of the neutralizing epitope recognized by monoclonal antibodies.

Monoclonal antibodies (MAbs) 2D4, 2D6, and 13D6 against human herpesvirus 6 (HHV-6) variant A strain GS recognized virion envelope glycoprotein complex gp82-gp105 and neutralized the infectivity of HHV-6 variant A group isolates. A 624-bp genomic fragment (82G) was identified from an HHV-6 strain GS genomic library constructed in the lambda gt11 expression system by immunoscreening with MAb 2D6. Rabbit antibodies against the fusion protein expressed from the genomic insert recognized glycoprotein complex gp82-gp105 from HHV-6-infected cells, thus confirming that the genomic fragment is a portion of the gene(s) that encodes gp82-gp105. This genomic insert hybridized specifically with viral DNAs from HHV-6 variant A strains GS and U1101 under high-stringency conditions but hybridized with HHV-6 variant B strain Z-29 DNA only under low-stringency conditions. DNA sequence analysis of the insert revealed a 167-amino-acid single open reading frame with an open 5' end and a stop codon at the 3' end. Hybridization studies with HHV-6A strain U1102 DNA localized the gp82-gp105-encoding gene to the unique long region near the direct repeat at the right end of the genome. To locate the neutralizing epitope(s) recognized by the MAbs, a series of deletions from the 3' end of the gene were constructed with exonuclease III, and fusion proteins from deletion constructs were tested for reactivity with MAbs in a Western immunoblot assay. Sequencing of deletion constructs at the reactive-nonreactive transition point localized the epitope recognized by the three neutralizing MAbs within or near a repeat amino acid sequence (NIYFNIY) of the putative protein. This repeat sequence region is surrounded on either side by two potential N-glycosylation sites and three cysteine residues.

Amino Acid Sequence↗

PubMed1993

Evaluation of left ventricular functional status using thermodynamic indices.

Conventional methods to assess cardiac contractility have been focused on the mechanical properties of the myocardium. Many of these have suffered from theoretical and practical drawbacks. In this study, we have attempted to evaluate the left ventricular contractile status using the thermodynamic principle and compared these indices with the conventional index (dP/dt). A total of 8 mongrel dogs were anesthetized and artificially ventilated. A Millar catheter with high-fidelity multiple sensors was inserted into the aorta to record the simultaneous changes in aortic flow and pressure waves. Cardiac inotropy was increased by graded doses (2-32 micrograms/kg/min) of dobutamine. Angiotensin injection (100-300 micrograms) to achieve a blood pressure elevation of 30 mmHg was employed for afterload augmentation. Preload was increased by rapid infusion of 6% dextran solution (20 ml/kg). Several thermodynamic parameters were calculated at steady state during the control period and after drug interventions. These included power-averaged rate of power density generation (ARPD), peak ejection rate of change of power (PREP), energy-averaged power density (APD) and frequency-normalized ARPD (FARPD). PREP and APD were unchanged by afterload increment while FARPD, ARPD and dP/dt decreased significantly with an increase in afterload, ARPD was highly sensitive to an increased preload (p < 0.001), and PREP was also changed significantly by an increase in preload. dP/dt was boarderlinely affected by Dextran infusion (p = 0.05), and APD was independent of preload (P > 0.05). Inotropic stimulation increased ARPD, PREP, APD, FARPD and dP/dt by 139.0 +/- 48.0%, 98.0 +/- 51.4%, 74.0 +/- 49.7%, 60.0 +/- 30.4% and 44.6 +/- 10.4%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1993

Emergency department recognition of pulmonary embolism.

The cases of forty-six patients who were admitted via the Emergency Department (ED) with suspected pulmonary embolism (PE), during a ten-year period, were reviewed. Ventilation perfusion lung scans were done in all patients, and pulmonary angiography was performed in 26. Thirty-six PE patients (78%) were correctly diagnosed by emergency physicians. Ten patients (22%) were erroneously diagnosed at the ED but were proved otherwise after hospitalization. The average age of the patients was 54 years, with males dominantly 67%. Overall mortality rate was 8.7%. Predisposing risk factors for PE were documented in 20 patients (43%). Prior history of thrombophlebitis (17%) or pulmonary embolism (13%), and immobilization (13%) were significant. The most common clinical features were dyspnea (76%), pleuritic pain (74%) and hemoptysis (41%). Thirty patients (65%) had tachypnea and 20 patients (43%) had tachycardia. Chest radiographs were abnormal in 35 cases (76%), and abnormal ECG findings were noted in 27 patients (59%). However, these abnormalities of chest radiographs or ECG were not sufficiently specific to confirm or exclude the diagnosis of PE. Noninvasive or contrast venography for deep vein thrombosis were performed in 31 patients (67%), of whom 17 cases (37%) had positive results. All patient received anticoagulation treatment. And six patients had thrombolytic agents as well.

Adolescent↗

PubMed1993

Altered levels of mRNA encoding enzymes of hepatic glucose metabolism in septic rats.

We investigated whether the multiple pathophysiological signals generated in a peritonitis septic model alter the mRNA levels of glycolytic and gluconeogenic enzymes, and whether these alterations are associated with glucose dyshomeostasis. Rats were sham-operated in the control group, and peritonitis sepsis was produced by a 1 cm cecal incision in the septic group. At 2, 4, and 6 hr post-surgery, total cellular RNAs were isolated from livers, and Northern blots performed to measure mRNA levels of aldolase B (ADL), lactate dehydrogenase (LDH), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), and glucokinase (GK). Hepatic PEPCK enzymatic activity was measured by condensing 14CO2 with phosphoenolpyruvate (PEP) to form malate. Serum glucose concentrations were also measured. We found the following: At 2 hr of peritonitis sepsis, serum glucose concentrations, mRNA levels of all enzymes, and PEPCK enzymatic activity increased over control levels. At 4 hr of peritonitis sepsis, serum glucose concentrations and mRNA levels of GK and PK continued to increase; mRNA levels of all other enzymes, as well as PEPCK enzymatic activity decreased to or below control levels. At 6 hr of peritonitis sepsis, serum glucose concentrations, mRNA levels of all enzymes, and PEPCK enzymatic activity decreased to or below control levels. We concluded that sepsis affects mRNA levels of glycolytic and gluconeogenic enzymes at the transcriptional level, and that these alterations are associated with glucose dyshomeostasis.

Animals↗

PubMed1992

Immunoelectron microscopy of carbonic anhydrase isozyme VI in rat submandibular gland: comparison with isozymes I and II.

Carbonic anhydrase (CA) was purified from the saliva of pilocarpine-treated rats by inhibitor-affinity chromatography, and its localization in the rat submandibular gland was studied by the indirect immunoperoxidase technique using a monoclonal antibody (MAb) raised against the enzyme. SDS-polyacrylamide gel electrophoresis of the CA VI gave three bands of 33, 39, and 42 KD. Enzyme digestion experiment showed that the 42 KD molecule was degraded into the 39 KD molecule and the 39 KD molecule into the 33 KD molecule. The cleavage of the 42 KD molecule was independent and that of the 39 KD molecule was dependent on endo-beta-N-acetylglucosaminidase F. The 42 KD molecule was detected in the CA purified from the pilocarpine-treated but not the untreated salivary gland. The MAb recognized all the three components of the enzyme. Immunostaining for CA VI was seen in the cytosol and secretory granules of serous acinar cells and in the duct luminal contents. Staining specific for erythrocyte CA (CA I and CA II) was observed in the cytosol of the epithelial cells of granular, striated, and excretory ducts. Among these duct cells, the agranular varieties in the granular and excretory ducts were essentially devoid of the immunoreactivity.

Animals↗

PubMed1992

Surgical management of an unusual osteomyelitis involving posterior elements in lumbar spine. A case report.

Improper and invasive management of low back pain may lead to an unexpected tragedy, vertebral osteomyelitis. A 30-year-old female patient suffering from low back pain after a lumbar strain called on a herbal therapist and was given a herb massage with some unknown medication. Unfortunately, a persistent painful ulcer with discharge developed over her back. She was referred to our clinic shortly after where x-ray showed bony destruction over the spinous process, facet, and lamina of L4. Fistulectomy, debridement and spinal fusion were performed. A satisfactory outcome was finally achieved.

Adult↗

PubMed1992

Traumatic tension pneumocephalus--intracerebral pneumatocele: a case report.

An 18-year-old Chinese man, suffering from head injury in a motorcycle accident, with right traumatic frontal intracerebral hemorrhage and frontal bone fractures, underwent emergency craniotomy with evacuation of hematoma at a local out-patient clinic and three months later, he suffered from CSF rhinorrhea. Headache, nausea and vomiting developed a week prior to admission. Tension pneumocephalus was diagnosed by computed tomography (CT) scan and plain skull X-ray. The fistula tract of the ethmoid sinus was investigated by radioisotope albumin (RISA) cisternography. The patient subsequently underwent emergency craniotomy for decompression. During the operation, we found that the intracerebral pneumatocele in the right frontal lobe communicated with the ipsilateral ethmoidal sinus, through which extracranial air ingressed and CSF egressed. This pneumatocele was unroofed and the fistula was temponaded by pericranial muscles and the Gelfomas sealed by tissue glue. Finally duraplasty was performed. Follow-up CT scan revealed that pneumocephalus subsided and the patient was cured of CSF rhinorrhea on discharge. As a surgical emergency, tension pneumocephalus can be successfully treated only by early diagnosis and early treatment.

Adolescent↗