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Biomedical subjects

E Yap

Publications and source records attributed to E Yap.

At least 19 recordsLinked to original sources
PubMed2006

Relationship between common functional polymorphisms of the p22phox gene (-930A > G and +242C > T) and nephropathy as a result of Type 2 diabetes in a Chinese population.

OBJECTIVE: Genetic determinants are important in diabetic nephropathy (DN). Oxidative stress has also emerged as an important pathogenic factor in DN and vascular NADH oxidase is a major source of reactive oxygen species (ROS). Previous small studies reported a strong but contradictory association between functional genetic variation of p22(phox), an important subcomponent of NADH oxidase, and DN. We investigated the association between two common functional single nucleotide polymorphisms (SNPs) (-930 A > G and +242 C > T) and DN in a much larger group of Chinese patients with Type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Case-control study of Chinese subjects with long-standing T2DM (> 10 years). Cases (n = 306) were subjects with a spot urinary albumin : creatinine ratio (ACR) of > 113 mg/mmol or elevated serum creatinine. Control subjects (n = 306) had ACR < 3.3 mg/mmol and normal serum creatinine. Genotyping was carried out by standard PCR and restriction fragment length polymorphism analysis. RESULTS: Gender distribution, age, duration of diabetes and HbA(1c) were similar in cases and control subjects. Distribution of genotypes in the control subjects for both SNPs was consistent with the Hardy-Weinberg equilibrium. Distribution of genotypes did not differ significantly between cases and control subjects for both polymorphisms-+2424C > T: cases CC 84.6%, CT 15.0%, TT 0.4% and control subjects CC 87.6%, CT 11.8%, TT 0.6% (P = 0.45); -930 A > G: cases AA 40.5%, AG 41.8%, GG 17.7% and control subjects AA 38.2%, AG 49.0%, GG 12.8% (P = 0.12). Distribution of alleles was also similar-+2424 C > T: cases C 92.2%, T 7.8% and control subjects C 93.5%, T 6.5% (P = 0.66); -930 A > G cases A 61.4%, G 38.6% and control subjects A 62.7%, G 37.3% (P = 0.38). We estimated that our study has approximately 80% power to detect a relative risk of 1.65 (for +242 C > T) and 1.35 (for -930 A > G) conferred by the minor allele, respectively. CONCLUSIONS: In contrast with previous small studies, our data suggest that these SNPs do not confer significantly increased susceptibility to DN secondary to T2DM in Chinese subjects.

Aged↗
PubMed2006

Association of renal function and delta-aminolevulinic acid dehydratase polymorphism among Vietnamese and Singapore workers exposed to inorganic lead.

OBJECTIVES: To investigate the effect of delta-aminolevulinic acid dehydratase (ALAD) polymorphisms on the association between blood lead and renal function among Vietnamese and Singaporean workers who were exposed to low to medium levels of inorganic lead, and to study the distribution of ALAD polymorphism among Vietnamese, Chinese, Malays and Indians. METHODS: A total of 459 male and female workers were studied. Blood and urine were collected for each worker in order to determine ALAD genotype, blood lead, and urinary delta-aminolevulinic acid (ALAU). Renal function tests included urine albumin (Ualb), urine beta2 microglobulin (Ubeta2m), urinary alpha1 microglobulin (Ualpha1m), N-acetyl-glucosaminidas (NAG), and urine retinol blinding protein (RBP). A multiple regression model with interaction term was applied to fit the entire data and to explore the modifying effect of ALAD polymorphism on the relation of blood lead to each renal function parameter. RESULTS: ALAD1-1 was the predominant genotype for all the ethnic groups while ALAD2-2 was the rarest. The frequency of ALAD2 allele was higher among Malays (8.8%) and Indians (10.6%) compared to the Chinese (5.0%) and Vietnamese (4.3%). The geometric mean of blood lead for all workers was 19.0 microg/dl. The models for Ubeta2m, Ualpha1m, and NAG showed that the ALAD1-2/2-2 group had higher beta coefficients than the ALAD1-1 group. Corresponding to 10 microg/dl blood lead, ALAD1-1 homozygotes had an increment of 1.288 microg/g Cr, 1.175 mg/g Cr, and 1.995 U/g Cr for Ubeta2m, Ualpha1m, and NAG, respectively. ALAD1-2/2-2 subjects had higher increments of 3.802 microg/g Cr, 2.138 mg/g Cr, and 3.89 U/g Cr for Ubeta2m, Ualpha1m, and NAG, respectively. CONCLUSION: The frequency of the ALAD2 allele is as low in Vietnamese workers as in Chinese. Workers with the ALAD2 allele appeared more susceptible to the effects of lead (especially at higher levels) on renal function.

Acetylglucosaminidase↗
PubMed2005

Changes in cerebral hemodynamics and cerebral oxygenation during surgical evacuation for hypertensive intracerebral putaminal hemorrhage.

OBJECTIVES: The aim of this study was to evaluate the changes in cerebral hemodynamics, tissue oxygenation and blood flow before and after surgery for spontaneous intracerebral hematomas. METHODS: Eleven patients who underwent surgical decompression of spontaneous putaminal hematoma were studied. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygen (PtiO2), and carbon dioxide tensions (PtiCO2), brain pH and regional cerebral blood flow (rCBF) were recorded prior to removing the bone flap and then on skin closure on completion of the operation. RESULTS: Following surgical decompression, mean ICP decreased significantly (P < 0.05); mean CPP, PtiO2, brain pH and rCBF improved although the changes were not significant. CONCLUSION: Surgical decompression for spontaneous intracerebral hematomas leads to significant reductions in ICP. This is accompanied by improvements in CPP, PtiO2 and rCBF in the penumbra.

Aged↗
PubMed2004

Alpha-synuclein haplotypes implicated in risk of Parkinson's disease.

The authors examined four- and six-loci haplotype constructs (from five single nucleotide polymorphisms and three microsatellite regions) of the alpha-synuclein gene in patients with Parkinson's disease (PD) and controls in an ethnic Chinese population. Logistic regression analysis demonstrated an association of NACP-Rep1 (p = 0.002) and L478 (p < 0.0001) with risk of PD after correction for the effects of age, sex, and the other polymorphic loci. Specific four-loci and six-loci haplotypes were significantly associated with an increased or decreased risk of PD.

Adult↗
PubMed2004

Spermine reduces infarction and neurological deficit following a rat model of middle cerebral artery occlusion: a magnetic resonance imaging study.

The role of nitric oxide (NO) in post-ischemic cerebral infarction has been extensively examined, but few studies have investigated its role on the neurological deficit. In the present study, we investigated the effect of spermine on the temporal evolution of infarct volume, NO production and neurological deficit using magnetic resonance imaging in a model of permanent focal cerebral ischemia in rats. Spermine given at 10 mg/kg 2 h after ischemia reduced the infarct volume by 40% and abolished brain NO production and improved the neurological score 24 h, 48 h and 72 h after ischemia. Spermine also reduced the neurological deficit as evaluated by rotamex, grip strength and neurological severity score tests.

Analysis of Variance↗
PubMed2001

Academic achievement, close up work parameters, and myopia in Singapore military conscripts.

AIM: To determine the relation of refractive error to environmental factors, including close up work, in Singapore military conscripts. METHODS: A cross sectional study was conducted on 429 Singapore military conscripts. Non-cycloplegic refraction and A-scan biometry were performed in both eyes. A detailed questionnaire was administered by in-person interview to obtain information about current and past near work activity, extra tuition lessons, educational experiences, and family demographics. RESULTS: Myopia associated with the conscript having been educated in the (gifted, special, or express) educational streams (adjusted odds ratio (OR) = 3.8, 95% confidence interval CI 2.0-7.3), and having completed pre-university education (OR=4.1, 95% CI 1.9-8.8). The reported close up work activity at age 7 years did correlate with age of onset of myopia (p<0.001). In parallel, supplemental tuition lessons in primary school has (OR=2.6, 95% CI 1.4-4.9) associated with conscript myopia. Parental myopia was positively associated with myopia (p<0.001), but this relation disappeared when adjusted for environmental factors. Current (p=0.83) and past close up work activity at age 7 years (p=0.13) did not correlate with myopia. CONCLUSION: Educational level and educational stream positively related to myopia. A relation was observed with reported close up work activity in early childhood and with tuition classes during elementary school, but not with current close up work activity. These results underscore the strong influence of environment in myopia pathogenesis but a role for close up work activity remains indeterminate.

Adult↗
PubMed2000

Myopia: gene-environment interaction.

INTRODUCTION: Myopia has reached epidemic proportions in Japan, Hong Kong, Taiwan and Singapore. This review summarises the evidence for environmental and genetic factors as well as gene-environment interaction for myopia for both epidemiologic studies as well as animal models. METHODS: A literature review was conducted after a Medline search on articles on the genetic or environmental aetiology of myopia in animal or epidemiologic studies. Articles on the methodology of gene-environment studies were also reviewed. All articles reviewed were articles published in peer-reviewed journals. RESULTS: Cross-sectional studies have found a positive association between myopia and near work activity such as reading and writing. Likewise, laboratory research has shown that environmental factors such as visual deprivation may lead to the development of myopia in animals. While linkage studies in humans are currently being conducted to identify possible markers for myopia in the human genome, several neurotransmitters, modulators and growth factors that influence refractive development have already been identified in animal models that may help identify candidate genes. Epidemiologic studies have also evaluated the combined effects of hereditary factors, environmental factors and gene-environment interaction on myopia development. CONCLUSIONS: Both genes and environmental factors may be related to myopia. There are no conclusive studies at present, however, that identify the nature and extent of possible gene-environment interaction. Further linkage analysis, affected sib-pair studies, and family-based association studies may better identify the nature of gene-environment interaction.

Animals↗
PubMed1998

Cauda equina syndrome after spinal anaesthesia in a patient with severe vascular disease.

PURPOSE: Spinal anaesthesia is selected for many lower extremity surgical procedures each year in the United States with a high degree of safety and efficacy. Even when adverse neurological outcomes have occurred, anatomical abnormality or coagulopathy have been implicated in the majority of cases. Epinephrine is used in high concentrations in many of these anaesthetics to increase the duration and intensity of the block. Although epinephrine is known to decrease spinal cord blood flow, its use in normal patients has not caused complications. We report a case where spinal anaesthesia with bupivacaine and epinephrine resulted in anterior spinal artery compromise and the development of a cauda equina syndrome postoperatively. CLINICAL FEATURES: A 57-yr-old man with severe coronary artery and peripheral vascular disease was scheduled for incision and drain of an abscess of the left thigh. He received an atraumatic dural puncture and injection of 12.5 mg bupivacaine with 0.2 ml 1:1000 epinephrine. During onset, he experienced a severe, painful sensation of the thighs which resolved with development of the block. Postoperatively, he was noted to have exacerbation of proximal muscle weakness and decreased perineal sensation and rectal tone. Subsequent EMG studies demonstrated proximal neuron loss consistent with cauda equina syndrome, presumed to be related to insufficiency of the anterior spinal artery. CONCLUSION: Routine use of epinephrine in spinal anaesthesia for patients with multi-organ vascular disease should be considered carefully because of the possibility of vascular insufficiency of the spinal cord which would be exaggerated by the vasoconstrictive effect of epinephrine.

Anesthesia, Spinal↗
PubMed1997

Molecular genetic analysis of TGF-beta1 in ovarian neoplasia.

Malignant ovarian tumours have been associated with a loss of autocrine growth inhibition by transforming growth factor-beta. This study aimed to detect abnormalities in the gene structure, expression and localization of TGF-beta1, in paraffin-embedded samples from 31 ovarian neoplasias (21 malignant, 5 borderline and 5 benign). Gene mutations in the region coding for the active protein were detected by PCR-SSCP analysis of exons 5, 6 and 7. mRNA expression and localization was studied by nonisotopic in situ hybridization (NISH) using cDNA probes generated by the reverse transcriptase polymerase chain reaction (RT-PCR), and immunohistochemistry, using antibodies against both intracellular and extracellular (matrix-associated) forms of TGF-beta1. Four mutations were found: one in exon 6 (serous adenocarcinoma), one in exon 7 (Mullerian tumor), and two in exons 5 and 6 from a serous cystoadenoma. TGF-beta1 mRNA was expressed in 87% and proteins in 90% of ovarian tumours. Most tumours expressing large amounts of TGF-beta1 mRNA, also contained a large number of protein binding sites. In malignant tumors, TGF beta1 was more strongly expressed in high-grade ovarian carcinomas with a cystic-papillary pattern than in tumours with a solid growth pattern. Normal ovarian tissue (follicles, granulosa cells) adjacent to tumor showed weak epithelial labeling and staining. Gene mutation did not correlate with histological type of tumor, mRNA or protein expression. TGF-beta1 mutation and abnormalities in its expression seem to occur in benign and malignant ovarian tumors, and could be involved in their pathogenesis. TGF beta1 gene mutations may act in multistage ovarian neoplasia, by reducing epithelial cell responsiveness to TGF-beta1 negative growth control.

Adenocarcinoma↗
PubMed1997

Molecular genetic analysis of TGF beta1 in breast cancer.

Conflicting data suggest that TGF-beta1 can either inhibit or promote the progression of breast cancer. To determine the biological role of TGF beta1 in mammary carcinoma, in this study we examined the gene structure, expression and localization of TGF-beta1 using paraffin-embedded samples from 32 (27 IDC, 1 ILC, 1 DCIS, 1 ADH) breast lesions. Gene mutations in the region coding for the active protein were investigated by PCR-SSCP of exons 5, 6, and 7. mRNA -TGF-beta1 expression and distribution was examined by NISH using cDNA probes generated by RT-PCR and immunohistochemistry. We detected two mutations in exon 6 TGF-beta1 from IDC; and TGF beta1 mRNA and proteins in 28 (87%) of the tumors. Invasive breast carcinomas had more intense TGF-beta1 activity than CIS and than normal tissue adjacent to tumor. TGF beta1 mRNA and proteins were higher at the edge of the tumor than in the center and were also higher in less differentiated breast neoplasms. TGF-beta1 mRNA transcription and protein levels did not correlate either with TGF-beta1 exon 6 mutation or type and grade of differentiation of breast tumors. These observations suggest that TGF beta1 mutations in breast neoplasms might cause loss or inactivation of the growth inhibitory effects of TGF-beta1. They also support the proposed role of TGF-beta1 in the pathogenesis of breast cancer.

Breast Neoplasms↗
PubMed1997

TGF-beta1 in colonic neoplasia: a genetic molecular and immunohistochemical study.

Transforming growth factor-beta proteins are key regulators of cellular growth and differentiation. To understand the role of TGF-beta in colonic tumour progression, 47 paraffin embedded samples from colonic tumours (13 adenomas, and 34 adenocarcinomas) were studied. Gene mutations in the region coding for the active protein were studied by PCR SSCP analysis of exons 5, 6, and 7. TGF-beta1 mRNA expression and localization were studied by NISH using cDNA probes generated by RT-PCR. Protein distribution was investigated by immunohistochemistry using antibodies against both intracellular and extracellular forms. Three mutations were found: one in exon 5 (Dukes C) and two in exon 7 (Dukes C and A). TGF-beta1 mRNA was observed in 9 (69%) of 13 adenomas and in 30 (88%) of 34 adenocarcinomas. Levels of TGF-beta1 mRNA and proteins were higher in colorectal carcinomas than in colorectal adenomas. Tubular adenomas associated with dysplasia showed greater expression of TGF-beta1 than adenomas without dysplasia and than non-neoplastic colonic mucosa. In dysplasia and cancer, epithelial neoplastic cells and stromal cells were positive for TGF-beta1. In normal tissue endothelial cells and granulocytes sporadically showed immunoreactivity for TGF-beta1, whereas epithelial cells were all negative. The three mutations in TGF-beta1 exons 5, 6 and 7 found in colorectal adenocarcinomas suggest that TGF-beta1 mutation may play a role in colorectal carcinogenesis and that the presence of the mutant form contributes to the transformed state. Our two other findings, the loss of staining gradient in normal colonic mucosa and the higher levels of TGF-beta1 mRNA and proteins in colorectal carcinomas than in colorectal adenomas, indicate that the de-regulation of TGF-beta1 expression may occur as an early event in colorectal carcinogenesis. Although TGF-beta1 expression is generally a reflection of cellular differentiation, tumour grade is not associated with TGF-beta1 mRNA expression. Beside being present in the epithelial cells of the colonic tumours, TGF-beta1 mRNA also occurred in the stroma: its localization in the macrophages adjacent to tumour strongly suggests that TGF-beta1 could be secreted by macrophages. This hypothesis should lead to new therapeutic strategies for colorectal carcinoma.

Adenocarcinoma↗
PubMed1996

Increased expression of the cyclin D1 gene in Barrett's esophagus.

Previous studies have found a 3-10-fold amplification and overexpression of the cyclin D1 gene in about 32% of human esophageal squamous cell carcinoma. The purpose of this study was to evaluate the prevalence of increased expression of the cyclin D1 protein in Barrett's esophagus. Using 69 formalin-fixed and paraffin-embedded human esophageal specimens, which had been removed endoscopically or obtained at surgery during 1993 and 1994, all immunohistochemical analyses were performed using an avidin-biotin complex immunoperoxidase technique. Increased nuclear expression of the cyclin D1 protein was noted in 32 of 69 samples (46%; 44% of the samples from males and 50% of the samples from females). Positive nuclear staining for the cyclin D1 protein in Barrett's disease with intestinal metaplasia was found in 38% of the male cases and 25% of the female cases, whereas in gastric metaplasia it was positive in 33% of men and 48% of women. Nuclear accumulation of the cyclin D1 protein was also found in both dysplastic and nondysplastic lesions, and it was not associated with sex, age, or cigarette or alcohol consumption. Samples from patients taking proton pump inhibitors tended to be less frequently positive (32%) for cyclin D1 nuclear staining when compared to patients taking H2 antagonists (45%) or antacids (55%). These studies suggest that increased expression of cyclin D1 is an early event in the tumorigenic process of esophageal adenocarcinomas and that the increased expression of this gene might predispose the epithelium to malignant transformation.

Adenocarcinoma↗
PubMed1991

Do our guardians need guarding? An examination of the Australian system of self-regulation of alcohol advertising.

In this study the Australian system of self-regulation of alcoholic beverage advertising was examined. Sixteen advertisements, eight print and eight television advertisements, were subjected to public scrutiny. Respondents rated advertisements using a self-completion questionnaire based directly on the Australian Alcoholic Beverage Advertising Code. Responses were collated and where a majority of respondents had endorsed items that constituted a breach of the cose, a complaint, ostensibly from a member of the general public, was made to the Advertising Standards Council. All sixteen advertisements were regarded by the public as containing aspects which breached the code. However, the Advertising Standards Council rejected all but one of the sixteen complaints, often directly contradicting the opinions of our respondents. The social policy implications of these results are considered. It is contended that the system of self-regulation of alcohol advertising does not serve the public interest.

Journal Article↗