Search PubMed⌕ Search

Biomedical subjects

K W Chang

Publications and source records attributed to K W Chang.

At least 37 records · Page 2Linked to original sources
PubMed2000

Alterations of adenomatous polyposis Coli (APC) gene in oral squamous cell carcinoma.

The present study assessed the roles of Adenomatous Polyposis Coli (APC) tumor suppressor gene during oral carcinogenesis. Reduction of APC transcript levels and APC loss of heterozygosity (LOH) were found in 39% (7/18) and 29% (10/34) cases of oral squamous cell carcinoma (OSCC), respectively. The apparent APC heterozygosity (27%) in non-cancerous matched oral tissue (NCMOT) adjacent to OSCC at an exon 11 locus was significantly lower than normally found in the Taiwanese population (49%). These findings suggest that the allelic status of APC could indicate a cancer risk. No polymorphism of 11307 allele of APC was identified in NCMOT or OSCC. Our data indicated that alterations of APC are frequent molecular changes of OSCC. Advances in understanding of the APC alterations that accompany OSCC development might provide a means for early diagnosis and possibly new therapeutic strategies.

Carcinoma, Squamous Cell↗
PubMed1999

Differential response to benzo[A]pyrene in human lung adenocarcinoma cell lines: the absence of aryl hydrocarbon receptor activation.

Benzo[a]pyrene (B[a]P) has been shown to produce DNA adducts and to initiate pulmonary carcinogenesis in animals. We observed differential susceptibility to B[a]P in two human lung adenocarcinoma cell lines, A427 and CL3. DNA adducts were induced by B[a]P treatment in CL3 cells, however, A427 cells were much less responsive to B[a]P treatment. Cytochrome P450 1A1 (CYP1A1) is involved in bioactivation of B[a]P in nonhepatic tissues. Cotreatment with alpha-naphthoflavone, a CYP1A1 inhibitor, abolished DNA adduct formation by B[a]P in CL3 cells. Nevertheless, CYP1A1 inducer beta-naphthoflavone, enhanced DNA adduct formation by B[a]P in both A427 and CL3 cells. Both enzyme activity and mRNA levels of CYP1A1 were highly induced by 1 or 10 microM B[a]P treatment for 24 hr in CL3 cells but not in A427 cells. Protein levels of AhR and aryl hydrocarbon receptor nuclear translocator (Arnt) were similar in A427 and CL3 cells before B[a]P treatment. However, B[a]P induced a retarded band with the [32P]-dioxin responsive element in CL3 cells, but not in A427 cells. This study demonstrated that variation in AhR-mediated CYP1A1 induction contributes to differential susceptibility to B[a]P-DNA adduct formation in human lung cells. Since AhR and/or Arnt function is impaired in A427 cells, this cell line offers a model for investigating the repression mechanisms of CYP1A1 induction by B[a]P in lung cells.

Adenocarcinoma↗
PubMed1999

Safrole-like DNA adducts in oral tissue from oral cancer patients with a betel quid chewing history.

Betel quid (BQ) chewing has been associated with an increased risk of oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF). Piper betel inflorescence, which contains 15 mg/g safrole, is a unique ingredient of BQ in Taiwan. Chewing such prepared BQ may contribute to safrole exposure in human beings (420 microM safrole in saliva). Safrole is a known rodent hepatocarcinogen, yet its carcinogenicity in human beings is largely undetermined. In this study, using a (32)P-post-labeling method, we have found a high frequency of safrole-like DNA adducts in BQ-associated OSCC (77%, 23/30) and non-cancerous matched tissue (NCMT) (97%, 29/30). This was in contrast to the absence (< 1/10(9) nucleotides) of such adducts in all of non-BQ-associated OSCC and their paired NCMT (P < 0.001). Six of seven OSF also exhibited the same safrole-like DNA adduct. The DNA adduct levels in OSF and NCMT were significantly higher than in OSCC (P < 0.05). Using co-chromatography and rechromatography techniques, we further demonstrated that these adducts were identical to synthetic safrole-dGMP adducts as well as DNA adducts from 1'-hydroxysafrole-treated HepG2 cells. These results suggest that safrole forms stable safrole-DNA adducts in human oral tissue following BQ chewing, which may contribute to oral carcinogenesis.

Areca↗
PubMed1999

Telomerase activity and in situ telomerase RNA expression in oral carcinogenesis.

To investigate the role of telomerase in oral carcinogenesis, we assayed telomerase activity in various oral tissues by a modified telomeric repeat amplification protocol (TRAP) analysis. Also, using digoxigenin-labeled probes, we measured the in situ expression of human telomerase RNA component (hTR) in paired oral squamous cell carcinomas (OSCC) and adjacent non-cancerous matched tissue (NCMT). We detected telomerase activity in three OSCC cell lines, but not in primary oral keratinocytes. In patient samples, most OSCC (36/42, 86%) and oral premalignant lesions (8/12, 67%) possessed telomerase activity. In addition, 6 of 27 (22%) NCMT contained weak telomerase activity. In situ hybridization showed that hTR was expressed in almost all OSCC (23/27, 85%) as well as in the majority of NCMT (20/25, 80%). In most cases, accumulation of hTR was observed both in the nucleus and cytoplasm of epithelial cells. A correlation between hTR expression and more advanced tumor grade was observed. The appearance of telomerase activation and hTR expression during oral carcinogenesis was different. This study indicates that the activation of telomerase is an early and frequent event in OSCC.

Adult↗
PubMed1998

p53 alterations in betel quid- and tobacco-associated oral squamous cell carcinomas from Taiwan.

Alterations of p53 have been explored in Taiwanese oral squamous cell carcinomas (OSCCs) consisting of a betel quid (BQ)/tobacco-related subgroup of 36 subjects and a tobacco-related subgroup of 13 subjects. Mutations in conserved exons were found in 12 tumors. Seven mutations were clustered in a hot-spot region mapped to a region between codons 273-282 in exon 8. The incidence of p53 mutation in BQ/tobacco tumors was 22% (8/36). The frequency of p53 allelic loss (21%, 3/14) in BQ/tobacco tumors approximates to the incidence of mutation. This is the first study demonstrating allelic deletion of p53 in such malignancies. Twenty-four of 43 samples showed positive p53 immunostaining. All tumors harboring mis-sense mutations of p53 in conserved exons exhibited nuclear protein accumulation. The incidence of mutation in conserved exons in BQ/tobacco-associated Asian OSCCs (15%) is significantly different from worldwide OSCCs (46%) related primarily to tobacco consumption (P=0.00001).

Adult↗
PubMed1998

Pressure ulcers--randomised controlled trial comparing hydrocolloid and saline gauze dressings.

An open comparative randomised study comparing the performance of hydrocolloid dressings (DuoDERM CGF) to saline gauze dressings in the treatment of pressure ulcers was done to evaluate the overall dressing performance, wound healing and cost effectiveness. Thirty-four subjects were enrolled at the University Hospital, Kuala Lumpur over a 643 days period. Inclusion criteria were Stage II or III pressure ulcers, at least 18 years of age and written informed consent. Only one pressure ulcer per subject was enrolled in the study. Patients with infected pressure ulcers, diabetes mellitus, an immuno-compromised status and known sensitivity to the study dressings were excluded. Subjects who met the enrollment criteria were randomised to one of the two dressing regimes. They were expected to participate in the study for a maximum of eight weeks or until the pressure ulcer healed, which ever occurred first. Overall subject age averaged 58 years and the mean duration of pressure ulcer existence was about 1 month. Twenty-one of the thirty-four ulcers enrolled were stage II and thirteen were stage III. The majority of the ulcers (88%) were located in the sacral area and seventeen subjects (50%) were incontinent. In the evaluation of dressing performance in terms of adherence to wound bed, exudate handling ability, overall comfort and pain during dressing removal; all favoured the hydrocolloid dressing by a statistically significant margin (p < 0.001). Subjects assigned the hydrocolloid dressing experienced a mean 34% reduction from their baseline surface area measurement compared to a mean 9% increase by subjects assigned gauze dressings. This was not statistically significant (p = 0.2318). In cost evaluation of the study products, there was no statistical significance in the total cost of wound management per subject. When only labour time and cost was evaluated, there was a statistically significant advantage towards hydrocolloid dressings.

Adult↗
PubMed1998

Intestinal lymphangiectasia--a report of three Chinese children in Malaysia.

This is a report of 3 Chinese children with intestinal lymphangiectasia in Malaysia. Two children responded to a low fat diet and medium-chain triglyceride supplement. The third child has recurrent chylous ascites. None of the children has recurrent infections despite low CD4+ cells and low levels of IgG and IgA. Intestinal lymphangiectasia is a rare congenital disorder of the mesenteric lymphatic that leads to the obstruction of the lymphatics of the intestine and protein losing enteropathy. Restriction of dietary fat intake will usually result in remission. Recurrent chylous ascites is a problem and management can be difficult.

China↗
PubMed1996

The effects of continuous versus interrupted noise exposures on distortion product otoacoustic emissions in guinea pigs.

Distortion product otoacoustic emissions (DPOAE) were measured serially in guinea pigs before and following 4-h exposures to a half-octave band of noise centered at 6 kHz. Stimulus parameters used to elicit the DPOAE were f2/f1 = 1.26 and L2 = L1-10. The 80 dB SPL exposures resulted in attenuation of emissions, which was maximal at the frequency one-half octave above the exposure when referenced to the f2 stimulus, and which recovered back to baseline after 2 days. The 90 dB SPL exposures resulted in a permanent deficit in emissions elicited by high-frequency stimuli, as measured after 8 days of recovery. A statistically significant difference was also found between animals exposed continuously for 4 h versus animals given two 2-h exposures separated by a 1-h break. Measures of f2-f1 and 3f1-2f2 indicated that they were more sensitive than 2f1-f2 to alterations in cochlear function after noise exposure.

Acoustic Stimulation↗
PubMed1996

p53 and Ha-ras mutations in chemically induced hamster buccal pouch carcinomas.

Well-differentiated squamous cell carcinomas were induced in hamster buccal pouch epithelium by twice weekly topical applications of N-methyl-N-benzylnitrosamine (MBN) or 7,12-dimethylbenz[a]anthracene (DMBA) over a period of 15 weeks. Each of the 22 tumors induced (14 MBN and eight DMBA) were evaluated by single-strand conformation polymorphism and DNA sequencing to identify mutations in conserved exons (E5-E8) of the p53 tumor suppressor gene and codons 12/13 and 61 of Ha-ras. In addition, Northern blot analysis of 10 MBN tumors and five DMBA tumors was performed to determine whether the mdm-2 gene was overexpressed, p53 mutations were detected in five of 14 (35%) MBN-induced carcinomas and in two of eight (25%) DMBA-induced carcinomas. Ha-ras mutations were detected in three of 14 (21%) MBN-induced carcinomas and in three of eight (37%) DMBA-induced carcinomas. One MBN-induced carcinoma exhibited a mutation in both the p53 and Ha-ras genes. The majority (five of seven of p53/Ha-ras mutations induced by MBN were G->A transitions and two of these occurred at hamster p53 codon 248, which corresponds to human p53 codon 245, a known mutational tumor 'hot spot'. A->T transversion at Ha-ras codon 61 accounted for three of five (60%) DMBA-induced mutations. There was no evidence of mdm-2 overexpression in any of the tumors evaluated. Overall, the results provide additional support for the validity of the hamster buccal pouch model of oral carcinogenesis, as applied to sequential cellular and molecular analysis and cancer chemoprevention studies.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

MTS1 gene mutations in archival oral squamous cell carcinomas.

Multiple tumor suppressor gene 1 (MTS1) has been found mutated or deleted in a variety of human cancers. Our purpose was to identify and characterize MTS1 gene mutations in primary oral squamous cell carcinomas (SCCs) in each of the three exons of the MTS1 gene. Seventeen archival samples of oral SCC were evaluated for the presence of MTS1 mutations using single strand conformation polymorphism (SSCP) and DNA sequencing. Three of 17 tumors exhibited MTS1 gene mutations: one tumor exhibited a mutation in exon 2 and two tumors exhibited mutations at the splice site junction of intron 2 and exon 3. Three tumors also exhibited a common base change in the 3' untranslated region of exon 3, which is interpreted as a likely polymorphic variant. An examination of the three tumors exhibiting MTS1 point mutations revealed no unique characteristics relative to p53 immunohistochemical activity, mitotic frequency, or degree of histologic differentiation. This study indicates that MTS1 gene mutations may be involved in at least a minor proportion of oral SCCs.

Adolescent↗
PubMed1995

Multiple genetic alterations in hamster pancreatic ductal adenocarcinomas.

Pancreatic ductal adenocarcinomas induced in the Syrian golden hamster (SGH) by N-nitrosobis(2-oxopropyl)amine share many similarities with the human disease, including mutations of the K-ras oncogene. In vitro carcinogenesis studies with immortal SGH pancreatic duct cells indicate that neoplastic transformation in this system can occur without mutational inactivation of p53 suppressor gene. In this study we extend the genetic analysis of the in vivo SGH model to increase the number of cases analyzed for the status of K-ras and to determine further the spectrum of alterations involved; we have studied the status of the p53, DCC, and Rb-1 suppressor genes and the status of the mdm2 oncogene, which can involve p53 indirectly. The partial SGH-coding sequence of mdm2 and DCC was determined. K-ras mutation in the second position of codon 12 was present in 17 of 19 (90%) of tumors. Immunohistochemistry and single strand conformation polymorphism analysis showed no evidence of p53 mutation in 21 tumors. RNase protection assays showed overexpression of mdm2 in 5 of 19 (26%) tumors. Semiquantitative reverse transcription-PCR analysis showed a complete or partial loss of DCC expression in 10 of 19 (53%) neoplasms and of Rb-1 (42%) expression in 8 of 19 tumors when compared to matched controls. Deregulation of these genes appears to be significant in SGH pancreatic carcinogenesis as indicated by their frequencies. However, the fact that 6 tumors showed either only a K-ras mutation or the absence of alterations of the 5 genes analyzed indicates that additional as yet unstudied or unknown genes are also involved in SGH pancreatic duct carcinogenesis.

Animals↗
PubMed1994

Genomic p53 mutation in a chemically induced hamster pancreatic ductal adenocarcinoma.

This study investigates possible alterations in exons 5 through 8 of the p53 gene and altered p53 protein expression in the Syrian golden hamster model of pancreatic ductal adenocarcinoma. In the Syrian hamster p53 sequence, 1469 base pairs are presented for the genomic regions surrounding exons 5 through 8, along with the primer sequences specific for the enzymatic amplification of the individual exons. Single-stranded conformation polymorphism was analyzed on the products obtained by enzymatic amplification of hamster genomic DNA extracted from 2 transplantable pancreatic ductal adenocarcinomas, 6 groups of N-methylnitrosourea (MNU)-treated pancreatic duct cells, and 17 MNU-induced pancreatic ductal adenocarcinomas. The two transplantable adenocarcinomas were a well-differentiated ductal adenocarcinoma established from a N-nitrosobis(2-oxopropyl)amine-induced tumor and a poorly differentiated ductal adenocarcinoma established from a spontaneous tumor. An altered mobility indicated a conformational change in the first part of exon 5 in the solid form of the well-differentiated ductal adenocarcinoma. Direct sequencing of the amplified product revealed an A-->C transversion in codon 135, which corresponds to codon 132 in the human p53 gene. A conformational change in exon 7 was observed in 1 of 6 MNU-treated cell samples, and none of the 17 resultant tumors. Direct sequencing confirmed a deletion of one C of the three in codon 263, which generates a frameshift mutation. No conformational change was observed in any other products. Positive staining with PAb240 or DO7 antibodies against human p53 or with an antibody generated in our laboratory against the hamster p53 fusion protein was observed only in the solid form of well-differentiated ductal adenocarcinoma and in rare cells scattered in 4 of 28 MNU-induced tumors analyzed. This study provides a system to analyze p53 gene alterations in the hamster and is the initial report of a specific p53 mutation in a hamster pancreatic ductal adenocarcinoma.

Animals↗
PubMed1994

Iatrogenic hyponatremia: a cause of death following pediatric tonsillectomy.

Death following pediatric tonsillectomy is very rare. If deaths occur, they are most commonly due to bleeding or aspiration. In this presentation, we would like to illustrate another potentially lethal complication following the pediatric tonsillectomy, iatrogenic hyponatremia. We have encountered 3 patients who have developed post-operative hyponatremia. This has resulted in 2 deaths. The third patient was successfully treated and developed no permanent sequela. We will discuss the etiology and pathophysiology of post-operative hyponatremia including guidelines for administering fluid and electrolytes intra-operatively and post-operatively. We expect that fatal post-operative hyponatremia can be avoided in the pediatric tonsillectomy patients.

Child↗
PubMed1994

One Herbert double-threaded compression screw fixation of displaced type II odontoid fractures.

Surgical treatment of type II odontoid fractures (OFs) has usually entailed C1-2 arthrodesis rather than fracture fixation. An alternative treatment of direct screw fixation is used to treat the fractures for preservation of atlantoaxial rotation. Type II OFs that cannot be completely reduced by close means are generally believed to be a contraindication for anterior screw fixation. Seven patients (group I) with displaced type II OFs that could be completely reduced were treated with fracture fixation by one 4.5-mm double-threaded compression screw and five patients (group II) with displaced type II OFs that could only be partially reduced were treated with fracture fixation by one 3.0-mm double-threaded compression screw. All patients had a minimum of 1-year follow-up. No major complications occurred. No loss of reduction occurred in group I patients. Group II patients had an average loss of reduction of 0.8 mm anterior displacement and 5 degrees anterior angulation. The overall rate of fracture union was 100%, and fracture resolution averaged 4.1 months. Ten patients had a normal range of cervical rotation, and there was no difference in preservation of cervical rotation between the two groups. Our results suggest that close reduction and compressive osteosynthesis by one double-threaded compression screw is an optimal method of treatment for displaced type II OFs that can be completely reduced and for some cases that can only be partially reduced. A 100% rate of fracture union and preservation of cervical rotation are the major advantages of this method. However, significant complications have been reported by other investigators. (ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Intraosseous screw fixation of anterior cervical graft construct after diskectomy.

This article describes a new technique of intraosseous screw fixation of the cervical spine, as well as a retrospective review of 27 patients who had anterior cervical interbody fusion after diskectomy and fixation with one intraosseous Herbert screw, with a minimum follow-up of 1 year. The study included 19 men and eight women. There were no neurologic complications at final follow-up evaluation. All patients had radiographic evidence of fusion. No screw breakage, back-out, or dislodgement occurred. Optimal intraoperative radiographic evaluation for accurate intraosseous screw placement is recommended. The use of intraosseous screw fixation is a useful addition to the armamentarium of the spine surgeon when fixation of anterior cervical graft after diskectomy is required. One hundred percent rate of union and prevention of complications related to the currently used anterior fixation systems are the major advantages of this method.

Adult↗
PubMed1994

Meconium ileus--a rare cause of neonatal intestinal obstruction in Malaysia.

Meconium ileus, rare in Malaysia, accounts for 3.7% of all neonatal intestinal obstructions (excluding imperforate anus) seen in the University Hospital, Kuala Lumpur, from 1980-1990. This paper retrospectively reviews our clinical experience with 5 cases of meconium ileus seen over a 12-year period from 1980-1991 in the University Hospital, Kuala Lumpur. Three of the neonates were Malays, and two were Punjabis. Four of them were full-term and one preterm. The birth weights ranged from 1900 to 3700 g, with a mean of 2670 g. One of them also had a sibling with meconium ileus. Two of them were found to have foetal ascites and one had intestinal obstruction, antenatally by ultrasonography. The remaining two were symptomatic soon after birth. Extensive calcification was observed on plain abdominal radiographs in three babies and dilated bowels in the other two. All of them underwent laparotomy and uncomplicated meconium ileus was confirmed in two cases, meconium peritonitis in two and one meconium pseudocyst in addition to meconium peritonitis. There was one intraoperative death, and one long-term survivor who did not have cystic fibrosis. The remaining three did not have additional features suggestive of cystic fibrosis, and finally succumbed to respiratory infection. Sweat test was not done to confirm the diagnosis for logistic reasons. The management of such patients proved to be a challenge to clinicians because of the rarity of this condition.

Female↗
PubMed1993

Oligosegmental correction of post-traumatic thoracolumbar angular kyphosis.

Seventeen patients with rigid throacolumbar angular kyphosis due to neglected fractures or dislocations were treated by a standardized single-stage monosegmental or bisegmental anterior discectomy and posterior closing extension wedge osteotomy. The two- or three-level reduction-fixation (RF) instrumentation was used posteriorly for correction and fixation. Choosing angled pedicle screws according to preoperative measurements, the method can always correct the kyphosis to the approximate sagittal curvature that is planned to create preoperatively. The average precorrection of thoracolumbar kyphosis was 39 degrees and was restored to 1.2 degrees for an average correction of 37.8 degrees (range, 22 degrees-56 degrees) with subsequent average loss of 1.1 degrees at final follow-up. Before operation, the complaints were slow progression of kyphotic deformities, fatigue, and pain. All these problems were solved by this procedure. Complications were minimal and mild. No neurologic complications occurred. Follow-up averaged 2.8 years. This method can correct rigid post-traumatic thoracolumbar angular kyphoses to normal geometric relationships as planned preoperatively without much negative effect in lumbar motion and any sacrifice of safety.

Adult↗