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Biomedical subjects

Y L Yip

Publications and source records attributed to Y L Yip.

15 recordsLinked to original sources
PubMed2006

Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase.

Nasopharyngeal carcinoma (NPC) is a common disease in Hong Kong and southern provinces of China. EBV infection is believed to play a critical role in the development of NPC. Previous studies on the transformation mechanism of EBV genes were mostly performed in either NPC or nonnasopharyngeal epithelial cells which may not be representative of premalignant nasopharyngeal epithelial cells. Establishment of a representative cell system would greatly facilitate the elucidation of the role of EBV infection in the development of NPC. Using telomerase alone, we were able to establish an immortalized nasopharyngeal epithelial cell line from primary nonmalignant nasopharyngeal biopsies. The telomerase-immortalized nasopharyngeal epithelial cells are largely diploid in karyotype. Interestingly, this newly immortalized nasopharyngeal epithelial cell line, referred as NP460hTert, harbors genetic alterations previously identified in premalignant and malignant nasopharyngeal epithelial cells. These include inactivation of p16 by homozygous deletion of the p16(INK4A) locus and downregulation of RASSF1A expression. The deletion of the p16(INK4A) locus appears to be the most crucial event for the immortalization of nasopharyngeal epithelial cells by telomerase and precedes RASSF1A downregulation. In addition, detailed analysis of the cytogenetic changes by conventional cytogenetics, spectral karyotyping (SKY) and array-based CGH revealed a gain of a 17q21-q25 fragment on 11p15 chromosome in all NP460hTert cells which occurred before deletion of the p16(INK4A) locus. Gain of 17q has been previously reported in NPC. In addition, activation of NF-kappaB was observed in immortalized NP460hTert cells at the later population doublings, and may play a role in the survival of immortalized NP epithelial cells. Id1 which is commonly expressed in various human cancers, including NPC, was also upregulated in the immortalized NP460hTert cells. Thus, the establishment of an immortalized nasopharyngeal epithelial cell line harboring common genetic alterations present in premalignant and cancerous nasopharyngeal epithelial cells may provide a valuable cell system to examine for early events involved in NPC carcinogenesis, particularly in elucidating the role of EBV infection in NPC development.

Cell Proliferation↗
PubMed2003

CD103+ intraepithelial lymphocytes--a unique population in microsatellite unstable sporadic colorectal cancer.

Colorectal cancers with microsatellite instability (MSI) typically show increased numbers of intraepithelial lymphocytes (IEL) in comparison to microsatellite stable (MSS) cancers. The aim of this study was to determine the phenotype of this unique lymphocyte population in MSI and MSS colorectal cancers. Twenty-four individuals with sporadic colorectal cancer (17 MSI, 7 MSS) were included in this study. Intraepithelial and stromal lymphocytes were detected using immunohistochemistry with anti-CD8 and anti-CD103 antibodies, and two observers independently quantified the numbers of lymphocytes. CD103+ (alpha E beta 7+) IELs detected within tumour tissue co-expressed CD8+ while the stromal lymphocytes were phenotypically heterogeneous, with respect to CD8+ and CD103+ expression. MSI colorectal cancers harboured increased numbers of CD8+ CD103+ IELs, as well as CD8+ CD103- and CD8+ CD103+ stromal lymphocytes, when compared with MSS colorectal cancers. CD103+ IELs were found at 27-fold greater numbers in the tumour epithelium than in normal epithelium from the same patient (P = 0.001, Wilcoxon matched pairs test). From our findings, we have proposed a mechanism for the homing of these alpha E beta 7+ lymphocytes to tumour tissue in MSI and MSS colorectal cancers.

Aged↗
PubMed2001

Comparison of phage pIII, pVIII and GST as carrier proteins for peptide immunisation in Balb/c mice.

Carrier proteins are important for improving the efficiency of synthetic peptide vaccines. Recently, genetically-based systems such as filamentous phage display or glutathione S-transferase (GST)-fusion proteins have been employed for immunisation. Whilst these carrier systems can facilitate the evaluation of a potential vaccine by reducing the time and cost of production, their relative efficacy and the kinetics of the immune response to each carrier has not been directly compared. In this study, we have displayed the epitopes of the anti-ErbB-2 Mabs N12 (C531-A586, EP531) and N28 (T216-C235, EP216) on phage minor coat protein pIII, major coat protein pVIII and GST. Balb/c H-2(d) mice were immunised with the constructs and the sera were tested after the initial, the 3rd, 5th and 6th immunisations for an anti-peptide, an anti-ErbB-2 and an anti-carrier response. The specificity of the antibody response was also mapped using synthetic peptides. It was found that GST was the best of the three carriers, both in terms of the magnitude and the kinetics of the induced anti-peptide and anti-ErbB-2 response. Multiple (five) administrations of the immunogens were necessary to obtain a high titre of antibodies specific for ErbB-2. It was further noted that whilst an anti-EP531 response was induced using all three carriers, EP216 was not immunogenic irrespective of the carrier used. The lack of immunogenicity of EP216 implies it does not contain a H-2(d) T cell recognition site. All three carriers provide a useful system for vaccination and consequently facilitate the identification of T-cell epitopes in Balb/c inbred mice.

Amino Acid Sequence↗
PubMed2001

Identification of epitope regions recognized by tumor inhibitory and stimulatory anti-ErbB-2 monoclonal antibodies: implications for vaccine design.

The self-oncoprotein ErbB-2 is overexpressed in a number of malignancies. The presence of endogenous anti-ErbB-2 Ab and T cell immune responses to this protein in cancer patients has made ErbB-2 an attractive target for active immunization. However, the finding that murine anti-ErbB-2 Abs can have stimulatory, inhibitory, or no effects on cancer cell growth suggests that an inappropriately induced immune response may have an adverse effect. To ensure the induction of a beneficial Ab response, it is important to identify the epitopes recognized by these Abs. In this study we have used phage-displayed ErbB-2 gene fragment libraries and synthetic peptides to epitope-map a panel of anti-ErbB-2 mAbs. The epitopes of three mAbs, N12, N28, and L87, were successfully located to C531-A586, T216-C235, and C220-C235 of ErbB-2, respectively. It was found that while N12 inhibited tumor cell proliferation, N28 stimulated the proliferation of a subset of breast cancer cell lines overexpressing ErbB-2. The peptide region recognized by N12, (C531-A586; EP531), was used as an immunogen to selectively induce an inhibitory immune response in mice. Mice immunized with the GST fusion peptide (GST-EP531) recognized the peptide region EP531 as well as native ErbB-2. More importantly, Igs purified from mouse sera were able to inhibit up to 85% of tumor cell proliferation. In conclusion, our study provides direct evidence of the function-epitope relationship of anti-ErbB-2 Abs and also emphasizes the value of inducing a potent tumor inhibitory polyclonal Ab response by rationally selecting regions of ErbB-2 used for immunization.

Amino Acid Sequence↗
PubMed1999

Biodistribution of filamentous phage-Fab in nude mice.

In vivo panning of peptide libraries in mice has allowed the isolation of peptides which target the vasculature of specific organs. The application of this approach to phage displaying Fab fragments (phage-Fab) could lead to the isolation of antibodies which recognize novel tumor antigens. In this study, we have evaluated the biodistribution of phage-Fab in nude mice. Balb/c nude mice were injected intravenously with 10(9) TU of phage displaying the anti-colon cancer Fab c30.6. Blood samples were collected at nine time points over a period of 72 h and three groups of four mice were sacrificed at 4 min, 24 h and 72 h. Normal tissues (liver, colon, spleen, kidneys, lungs, skeletal muscle) and faeces were collected at these time points and the number of viable phage in each sample was determined. The distribution of phage in tissues was also examined by immunohistochemical analysis of paraffin-embedded tissues. Regression analysis of plasma kinetic data showed that the half-life and the volume of distribution of phage was 3.6 h and 1 ml, respectively. Phage uptake occurred predominantly in lungs, kidneys, spleen and liver. Relatively few phage were distributed to colon and muscle, and phage were eliminated from the circulation by 72 h. Immunohistochemical analysis showed phage to be mainly within the vasculature at 4 min, whereas notable phage extravasation was observed at 24 h and 72 h. In conclusion, this study provides information on the in vivo behavior of phage-Fab which will be useful in the design of in vivo panning strategies. By choosing appropriate time points for tissue collection, it may be possible to isolate novel Fabs against both intra- and extravascular targets.

Animals↗
PubMed1999

Epitope discovery using monoclonal antibodies and phage peptide libraries.

Phage display is a biological system which facilitates the cloning and rapid selection of peptides from large combinatorial libraries. In comparison to the chemical combinatorial approach, the advantages of phage display lie in its simplicity and replicability. While phage display has many diverse applications, this review will focus on the use of phage peptide libraries to discover epitopes recognised by monoclonal antibodies. As monoclonal antibodies are useful tools for the detection of proteins and for the investigation of molecular interactions, the identification of their epitopes will serve to elucidate the structure and function of proteins, as well as aid in the discovery of new drugs and the development of vaccines.

Amino Acid Sequence↗
PubMed1997

Evaluation of different lymphoid tissue sources for the construction of human immunoglobulin gene libraries.

BACKGROUND: Phage display technology allows the isolation of novel human monoclonal antibodies. The technology relies on the construction of a recombinant antibody library and its display on phage particles. The quality of an antibody library is affected by several factors including the size, diversity and source of immunoglobulin genes. OBJECTIVE: The aim of the project was to determine the best tissue source for the construction of antibody libraries. STUDY DESIGN: Three tissue sources were used in this study: peripheral blood mononuclear cells from a healthy donor, Epstein-Barr virus (EBV) transformed peripheral blood mononuclear cells and lymph node tissue from individuals with breast cancer. The quality of each tissue source was assessed using two criteria: (1) the number of mature and activated B cells in each source; (2) the amount of immunoglobulin heavy and light chain genes amplifiable by polymerase chain reaction (PCR). RESULTS: EBV-transformed peripheral blood mononuclear cells and lymph node tissue were shown to contain more B cells than peripheral blood mononuclear cells. A relatively larger amount of immunoglobulin gene products could be amplified from EBV-transformed peripheral blood mononuclear cells and the lymph node. However, immunoglobulin containing gamma 1 chains could not be amplified from EBV-transformed mononuclear cells, and the resultant pattern of gene amplification suggests a possible selection bias. CONCLUSION: This study indicates that among the three tissue sources examined, lymph node tissue is the most suitable source for the construction of antibody libraries.

Antibodies, Monoclonal↗
PubMed1992

5 year statistics of animal and insect bites in Hong Kong.

Statistics of bites of patients in a rural district hospital in Hong Kong were accumulated over a 5 year period from 1984-1989. Analysis revealed a predominance of dog bites. Seasonal variations were noted for snake and insect bites, but not for dog bites. Comparison was made with some UK data.

Adolescent↗
PubMed1991

Quantitative analysis of the accuracy of linear array transrectal ultrasound in measurement of the prostate.

In 61 prostate autopsy specimens, linear array transrectal ultrasound and electronic vernier calipers were used to measure 3 maximal diameters along the longitudinal, anterior-posterior and transverse axes. The results were comparable. We assessed the reliability of empirical formulae, derived from various combinations of these 3 diameters, for the prediction of prostatic volume and weight. Formulae using all 3 diameters were accurate. The combination of longitudinal and anterior-posterior diameters, which was used clinically for prostate measurement, was less accurate.

Anthropometry↗
PubMed1988

Electrohydraulic lithotripsy of bladder stones. A Hong Kong experience.

Forty transurethral electrohydraulic lithotripsy procedures for bladder stones have been done. The rigid cystoscope was adequate in most cases but the rigid nephroscope was advantageous in large stones because of its larger bore and range of accessories. Use of the flexible cystoscope for stone extraction was difficult but it could be used with a few friable stones of less than 1 cm or for follow-up.

Adult↗
PubMed1986

Sigmoidoscopy with flexible electronic endoscopy: a preliminary experience in Hong Kong.

Eighty-two cases of electronic flexible sigmoidoscopy were performed from October 1984 to October 1985 in a rural hospital in Hong Kong. The scope is a relatively new type of flexible endoscope, which has no optical fibre bundle for imaging. The image is taken with a solid state television camera and relayed via a videoprocessor to a television monitor. The image quality and ease of handling were satisfactory. Acceptance by the endoscopy team and the patients was good. The differences in comparison with conventional fibrescopes and television systems are discussed.

Gastrointestinal Hemorrhage↗