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Biomedical subjects

J Yao

Publications and source records attributed to J Yao.

At least 235 records · Page 13Linked to original sources
PubMed1996

Molecular changes of colorectal cancer in Singapore.

Improved success in the management of colorectal cancer requires a better understanding of its development and biological behaviour. The key for this is molecular genetics. Gene changes parallel the multi-step changes in the adenoma-carcinoma sequence. Cancer results from a variable combination of defects in oncogenes, tumour suppressor, mutator and apoptotic genes. These changes are similar whether they occur in inherited disorders like adenomatous polyposis coli (APC) and hereditary non-polyposis colorectal cancer (HNPCC) or acquired cancer in the elderly. In Singapore, the c-myc and c-Ki-ras proto-oncogenes are found to be activated in 70% and 29% of tumours respectively. Allelic loss of chromosome 5q and 17p occurs in 25% and 70% of tumours respectively, while point mutation of the p53 tumour suppressor gene occurs in 50% of colorectal cancers. Both the frequency and the nature of the lesion occurring are compatible to the changes detected in Caucasian patients, suggesting common aetiological factors. The biological behaviour of colorectal adenocarcinomas is determined by the nature of defects or mutations in key genes such as the p53 tumour suppressor gene. Lymphatic spread is associated with the presence of point mutations and haematogenous spread is associated with loss of heterozygosity of p53. Survival is worse when conserved regions of the gene are mutated compared with those outside, and worst when codon 175 is mutated. Sensitivity to radiotherapy and chemotherapy is also determined by p53 mutation which controls apoptosis. Prognosis could now be individualised and with the prospect of gene therapy, molecular genetics will have a major impact on the management of colorectal cancer.

Adenocarcinoma↗
PubMed1996

Susceptibility of spontaneously hypertensive rats to the diabetogenic effects of streptozotocin.

Several studies have utilized the spontaneously hypertensive (SHR) diabetic rat to document the synergistic deleterious consequences of diabetes and hypertension on various organ systems. However, whether these effects are due entirely to the overlapping pathological states or partially result from a greater susceptibility of SHR rats to the diabetogenic effects of streptozotocin (STZ) is unclear. The present study was conducted to examine if strain-dependent variabilities in the STZ-induced diabetic state could also contribute to the pronounced complications previously observed in the SHR diabetic rat. To eliminate a possible modulating influence of severe hypertension on the beta-cytotoxic efficacy of STZ, SHR (SHRD), and Wistar (WisD) rats were injected with STZ (55 mg/kg i.v.) at 7-8 weeks of age, a time when there was no significant difference in systolic blood pressure between both stains. An oral glucose tolerance test was performed at 1 week following STZ and animals were killed at 2 weeks. Although both diabetic groups were equally hyperglycemic in the fed state, only SHRD rats had significantly elevated fasted glycemia at 1 week. Plasma insulin levels in the fed state or in response to oral glucose, as well as pancreatic insulin contents were diminished to a greater extent in the SHRD group relative to WisD. Fed plasma triglyceride (TG) levels were elevated only in the SHRD group, in association with a 4-fold reduction in basal circulating lipoprotein lipase (LPL) activity. However plasma TG clearance and LPL activity in response to i.v. heparin were not significantly altered in SHRD relative to SHR controls. The results in this study indicate that when evaluating the combined effects of diabetes and spontaneous hypertension, the STZ dose should be titrated to obtain an identical degree of diabetes in the SHR and a normotensive strain. In this regard, 45 (SHR) and 55 (Wistar) mg/kg STZ produced an identical milieu of diabetes.

Animals↗
PubMed1996

[Repair of acute thumb avulsion with the bi-lobed island flap of the second web].

The authors designed a bi-lobed island flap of the second web pedicled with the first and the second dorsal metacarpal arteries. Since 1993, five cases of acute thumb avulsion have been repaired using this flap. The size of the flaps ranged from 3 cm x 6 cm to 6 cm x 7 cm. All flaps survived with primary healing of the incisions. Three to nine months' follow-up showed that the flaps were thin and had sensation. The function and appearance of the reconstructed thumb were satisfactory. The bi-lobed island flap of the second web is a valuable method for the repair of thumb avulsion.

Adolescent↗
PubMed1996

[Treatment of severe hump nose].

An improved operative method has been used to treat severe hump nose in 6 cases since 1989. During the one-stage operation, the shape of the nose was remodeled by correcting the hump deformity and trimming the large lateral cartilage, alar cartilage and septal cartilage. Five cases obtained satisfactory results. One case had second operation because of callus hyperplasia. The article describes the operative design and main points of the procedure. The advantages of the method are discussed.

Adult↗
PubMed1996

[Synergism of three risk factors in hepatocellular carcinogenicity].

To evaluate potential synergistic effects of aflatoxin B1 (AFB1) hepatitis B virus (HBV) and hepatitis C virus (HCV) in the development of human primary hepatocellular carcinoma (PHC), AFB1, HBV-DNA and HCV-RNA in liver tissue sampled from the patients with PHC were detected by high performance liquid chromatography, nested polymerase chain reaction (PCR), and reverse transcription nested PCR. Positive rates of AFB1, HBV-DNA and HCV-RNA were 67.7% (21/31), 88.2% (60/68) and 13.2% (9/68), respectively. Eighteen of the 31 patients were positive for both AFB1 and HBV-DNA, and six of the 68 patients positive for both HBV-DNA and HCV-RNA. Furthermore, AFB1, HBV-DNA and HCV-RNA all were detected in four cases, while all negative in controls. It suggests that all the three factors are directly associated with human hepatic carcinoma, and play a synergistic role on hepatic carcinogenicity.

Adult↗
PubMed1995

Chronic elevation of S100 beta protein does not alter APP mRNA expression or promote beta-amyloid deposition in the brains of aging transgenic mice.

S100 beta protein, a member of a Ca(2+)-binding protein family present primarily in the nervous system, affects the survival and differentiation of both neurons and glia cells. Elevated levels of S100 beta protein have been observed in the brains of individuals with Alzheimer Disease (AD), as well as in those with Down Syndrome (DS). We have examined transcript levels from the gene encoding the amyloid precursor protein (APP) in four brain regions of mice from 1 to 24 months of age. After stable adult levels of expression are reached, APP mRNA levels do not change with aging. APP mRNA levels are independent of normal regional variation in S100 beta mRNA and protein. Further, chronic exposure to S100 beta elevated 2- or 7-fold above normal did not alter the transcript levels of APP in transgenic mice. These results leave open the possibility of focal changes in APP transcription and do not address possible effects of S100 beta on the complex processing known to occur with APP protein. However, neither control nor transgenic aged mice showed any evidence of abnormal deposition of amyloid in neuritic plaques. These results are discussed in the context of hypotheses about the role of elevated S100 beta in DS and AD.

Aging↗
PubMed1995

p53 point mutation and survival in colorectal cancer patients.

We have examined the relationship between point mutation of the p53 tumor suppressor gene and survival in colorectal cancer patients. We found that patients with tumors harboring mutated p53 genes showed a significantly poorer prognosis than did those patients with genes without point mutations, and, moreover, patient response to postoperative therapies depended significantly on mutation status in both adjuvant and palliative treatment cohorts. However, not all point mutations were the same functionally; point mutations within the conserved domains of the p53 tumor suppressor gene were inherently more aggressive than tumors with point mutations outside of these domains, and mutations of codon 175 were particularly aggressive. These results suggest that knowledge of a patient's p53 status, both with respect to the presence of point mutations and to the specific nature of the lesion, may be required to accurately predict both the course of the disease and the response of the disease to postoperative therapeutic interventions, especially those therapies based on the induction of apoptosis in the neoplastic cell.

Adenocarcinoma↗
PubMed1995

Analysis of high-mass biomolecules using electrostatic fields and matrix-assisted laser desorption/ionization in a Fourier transform mass spectrometer.

A new decelerating technique that places dc potentials on the orthogonal excitation and receiver plates as well as the rear trapping plate (conductance limit) of the source cell of a dual cubic cell has been applied to the standard matrix-assisted laser desorption/ionization Fourier transform mass spectrometry technique. When this five-plate trapping method is applied, high-mass ions with large translational kinetic energies can be trapped efficiently and detected. Using this approach, low-resolution spectra of carbonic anhydrase (MW = 29,000), egg albumin (MW = 45,000), and bovine albumin (MW = 66,000) have been obtained. Because the new decelerating method requires no modification to the existing cell, it is also possible to obtain high-resolution spectra for compounds with masses of ca. 14,000 Da and lower. Utilizing the five-plate trapping method, a bovine insulin spectrum with a resolving power of 20,000 was obtained. It is not yet possible to obtain higher resolution for the higher mass proteins. The reasons for this difficulty are currently being investigated.

Animals↗
PubMed1995

The potential role of fibroblasts in periprosthetic osteolysis: fibroblast response to titanium particles.

Periprosthetic osteolysis with or without aseptic loosening is a major clinical problem in total hip arthroplasty. While the macrophage response to prosthetic wear debris and its role in periprosthetic osteolysis has been extensively studied, information regarding other cell types (fibroblasts, osteoblasts) is limited. This study explored the response of fibroblasts to particulate wear debris. Fibroblasts isolated from interfacial membranes of patients with failed total hip replacements and normal synovial tissue, when challenged with small-sized ( < 3 microns) titanium (Ti) particles, responded with significantly enhanced expressions of collagenase, stromelysin and, to a much lesser extent, their tissue inhibitor of metalloproteinases (TIMP). These "regulated" expressions at both mRNA and protein levels were correlated with the size and composition of particles. De novo protein synthesis was required for the regulation of these mRNAs. A similar effect could be induced by the treatment of the cells with particle-free conditioned medium from Ti particle-stimulated fibroblasts. Furthermore, this conditioned medium significantly suppressed the mRNA levels of procollagen alpha 1 (I) and alpha 1 (III) in osteoblast-like MG-63 cells. It is concluded that fibroblasts stimulated with certain particle debris may play an important role in periprosthetic osteolysis by releasing bone-resorbing metalloproteinases and mediator(s) which resulted in suppressed collagen synthesis in osteoblasts.

Base Sequence↗
PubMed1995

1H, 13C and 15N chemical shift referencing in biomolecular NMR.

A considerable degree of variability exists in the way that 1H, 13C and 15N chemical shifts are reported and referenced for biomolecules. In this article we explore some of the reasons for this situation and propose guidelines for future chemical shift referencing and for conversion from many common 1H, 13C and 15N chemical shift standards, now used in biomolecular NMR, to those proposed here.

Carbon Isotopes↗
PubMed1995

Molecular cloning of a bovine ornithine decarboxylase cDNA and its use in the detection of restriction fragment length polymorphisms in Holsteins.

A cDNA coding for ornithine decarboxylase (ODC) was isolated from a bovine liver cDNA library. The clone (1758 base pairs) consisted of 5'- and 3'-untranslated regions of 185 and 187 nucleotides, respectively, and an open reading frame of 1383 nucleotides encoding an ODC protein (M(r) 51,342 daltons) of 461 amino acids. Comparison of the nucleotide and the predicted amino acid of the cDNA with other mammalian ODCs showed a very high degree of homology both at the DNA and protein levels. The bovine ODC mRNA was identified by northern blot to be a single species with a molecular size of 2.35 kilobase pairs. Primer extension analysis indicated that the 5'-untranslated region of the bovine ODC mRNA was 312 nucleotides long. Southern blot analysis of bovine genomic DNA revealed restriction fragment length polymorphisms when cleaved with restriction enzymes PstI, MspI, TaqI, and Bg/I.

Amino Acid Sequence↗
PubMed1995

Increases in CSF levels of interleukin-2 in schizophrenia: effects of recurrence of psychosis and medication status.

OBJECTIVE: Interleukin-2, traditionally viewed as solely involved in immunological events, has recently been shown to exert profound effects on the development and regulation of the central nervous system. This study examined the relationships between interleukin-2 in the CSF and plasma of schizophrenic patients and clinical measures, including relapse and medication status. Plasma and CSF interleukin-1 alpha levels were also measured to ascertain the specificity of changes in cytokine levels. METHODS: Seventy-nine physically healthy male patients with schizophrenia (DSM-III-R) received diagnostic evaluation and behavioral ratings. Haloperidol treatment was withdrawn for up to 6 weeks and patients were evaluated for symptom recurrence. CSF and plasma were obtained by established procedures before haloperidol withdrawal (N = 79) and after (N = 64). RESULTS: CSF levels of interleukin-1 alpha decreased significantly after haloperidol withdrawal but showed no relation to clinical status. In contrast, levels of CSF interleukin-2 were associated with recurrence of psychotic symptoms. Relapse-prone patients, examined both while medicated and after drug withdrawal, had significantly higher levels of CSF interleukin-2 than patients who did not relapse. CSF interleukin-2 level during haloperidol treatment was a significant predictor of worsening in psychosis. CONCLUSIONS: Levels of interleukin-2, a molecule that plays both neurodevelopmental and neuroregulatory roles, may have a role in relapse in schizophrenia. Levels of CSF interleukin-2 appear to be affected by relapse mechanisms, while peripheral blood levels are not. These changes are specific to interleukin-2, since levels of interleukin-1 alpha were affected by medication withdrawal but not by change in clinical state.

Adult↗
PubMed1995

[Simplified enzyme-linked immunoadsorbent assays for myelin basic protein and antibodies to myelin basic protein].

Synchronous quantitative determination using simplified enzyme-linked immuno adsorbent assay has been developed for myelin basic protein (MBP) and antibodies to myelin basic protein (Anti-MBP). Antisera were prepared by immunizing rabbits with purified MBP from human white matter. Antibodies to MBP was conjugated with horseradish peroxidase (HRP) by using modified periodate oxidation method. Minimum detection amounts of MBP and Anti-MBP are 0.25 ng/ml and 0.20 ng/ml respectively. The activities of Anti-MBP-HRP conjugates are stable (stored at -30 degrees C) for at least 2 years. The detection procedure can be accomplished within 24 hours.

Animals↗
PubMed1995

Differential effects of tumor necrosis factor-alpha on the expression of fibronectin and collagen genes in cultured bovine endothelial cells.

The effects of recombinant human tumor necrosis factor-alpha (TNF-alpha) on the expression of fibronectin and types (IV), (III), and (I) procollagen genes in cultured bovine pulmonary artery endothelial cells were examined in this study. Findings indicate that TNF-alpha increases steady-state levels of alpha l (IV) and alpha l (III) procollagen mRNAs while it decreases levels of fibronectin and alpha 2 (1) procollagen mRNA and leaves cytoskeletal actin mRNA levels unchanged. Both dose and exposure time moderated these effects. Treatment with TNF-alpha increased the stability of alpha l (IV) procollagen mRNA. The half-life of this mRNA, previously unreported in the literature, was increased by 118%, while the stability of fibronectin mRNA decreased by 44%. The stability of mRNAs for procollagens alpha l (III) and alpha 2 (I) were unchanged. Except in the case of procollagen alpha l (III), these effects were blocked by cycloheximide. Protein production induced by TNF-alpha was evaluated by immunoprecipitating proteins from the media and cell lysates. Our data indicate that TNF-alpha has a strong pretranslational regulatory role in cultured endothelial cell's expression of extracellular matrix protein genes.

Animals↗
PubMed1995

Measurement of acetabular version on the axiolateral radiograph.

There are 3 definitions of acetabular version: true (anatomic) version, planar (radiographic) version, and operative version. Although planar version can be measured on standard radiographs, the measurement may be inaccurate when applied to metal-backed acetabular components. However, another version angle is depicted clearly on an angled, cross-table lateral radiograph of the hip--the axiolateral view, and this angle readily distinguishes anteversion from retroversion. If the angle of the xray beam is known or is standardized, version measured on the axiolateral view can be converted to the other version angles. Nomograms for these conversions are presented. In most cases, acetabular version measured on the axiolateral radiograph closely approximates planar version.

Acetabulum↗
PubMed1995

Production of transforming growth factor-beta by cultured rat mesangial cells.

The purpose of this study was to examine whether transforming growth factor-beta (TGF beta) acts as an autocrine cytokine in cultured mesangial cells. Measangial cell conditioned media (CM) were prepared and tested for their effect on mesangial cell proliferation. CM showed a concentration dependent inhibition on mesangial cell proliferation and the activity was enhanced by treating conditioned media with acid. Gel filtration analysis showed peak inhibitory activity to reside in fractions with an estimated molecular weight range of 16-30 KD. The activity was partially blocked by anti-TGF beta antibody, but not nonimmune control IgG. The presence of TGF beta was confirmed using the mink lung epithelial cell assay. Furthermore, the addition of anti-TGF beta antibody directly into culture media significantly enhanced mesangial cell proliferation. These results demonstrate that measangial cell produce both active and latent forms of TGF beta, which functions as an autocrine growth inhibitor for mesangial cells.

Animals↗