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Biomedical subjects

S T Yuen

Publications and source records attributed to S T Yuen.

At least 55 records · Page 3Linked to original sources
PubMed1999

Histological changes during clearance of chronic hepatitis B virus infection by adoptive immunity transfer.

BACKGROUND: Serological clearance of hepatitis B surface antigen (HBsAg) has been described after reception of hepatitis B surface antibody positive marrow, via allogeneic bone marrow transplantation (BMT). Histological changes during the clearance of HBsAg are unknown. METHODS AND RESULTS: We described two chronic hepatitis B carriers (both hepatitis B e antigen negative), who cleared HBsAg after allogeneic bone marrow transplantation. Both received hepatitis B surface and core antibody positive human leucocyte antigen identical donors' marrow and had serological clearance of HBsAg 15 and 7 weeks after allogeneic BMT, respectively. Both events were preceded by hepatic flare. Both patients were also treated with famciclovir for the prevention of hepatitis B reactivation after BMT. Histological examination during the flare showed only mild necroinflammatory activity with multiple foci of confluent necrosis, associated with moderate lymphocytic infiltration. The majority of these lymphocytes were cluster of differentiation (CD) 8 positive. Using immunohistochemistry, there was no detectable hepatic expression of hepatitis B core antigen. However, HBsAg was positive, mainly in the area of confluent necrosis. Using in situ hybridization, hepatitis B virus (HBV) DNA was detected in the nucleus of 5% of hepatocytes, but not in the cytoplasm. CONCLUSIONS: At their last follow up, 22 and 16 months after BMT, the serum of both patients remained HBsAg negative, hepatitis B surface antibody positive and HBV-DNA negative by branched DNA assay.

2-Aminopurine↗
PubMed1999

Helicobacter pylori in Meckel's diverticulum with heterotopic gastric mucosa in a population with relatively high H. pylori prevalence rate.

BACKGROUND: Helicobacter pylori (H. pylori) colonize only foveolar gastric-type mucosa and are associated with active chronic gastritis and peptic ulcer. The aim of this study was to investigate whether H. pylori can also be found in Meckel's diverticulum which contains heterotopic gastric mucosa. METHODS: Biopsy specimens of Meckel's diverticulum resected in Queen Mary Hospital, University of Hong Kong, during the 10 year period 1986-1995 were retrieved and reviewed. Those containing gastric heterotopia were examined for the presence of H. pylori, using Warthin-Starry silver stain. RESULTS: In the 59 cases of Meckel's diverticula studied, 16 were found to contain heterotopic gastric mucosa. Helicobacter pylori were not identified in any of these cases. In one of the 16 patients a concomitant gastric biopsy was performed. Although the gastric mucosa of this patient was heavily colonized by H. pylori, again no H. pylori was found in the heterotopic gastric mucosa in the Meckel's diverticulum. CONCLUSIONS: The absence of H. pylori in all the Meckel's diverticula examined, even when the stomach was heavily colonized by the organisms, suggests that colonization of Meckel's diverticulum by H. pylori is a rare event. This, together with the overall rarity of H. pylori in all reported series of Meckel's diverticulum, argues against its causative role in complications of Meckel's diverticulum.

Adult↗
PubMed1999

Germline hMSH2 and differential somatic mutations in patients with Turcot's syndrome.

Turcot's syndrome is characterized clinically by the occurrence of primary brain tumor and colorectal tumor and has in previous reports been shown to be associated with germline mutations in the genes APC, hMLH1, and hPMS2. Here we describe three patients with Turcot's syndrome, each having colorectal adenocarcinoma and malignant glioma. All the colorectal and brain tumors from these patients showed replication errors in most of the microsatellite loci investigated. Search for underlying germline mutations in the nucleotide mismatch repair genes revealed three different hMSH2 mutations. All colorectal tumors showed a frameshift in the A(10) tract in the coding sequence of the transforming growth factor beta type II receptor (TGFBRII) gene, but no such change was detected in any of the brain tumors. Frameshift mutation in the BAX gene was found in one colon carcinoma and mutations in insulin-like growth factor type II receptor (IGFIIR) gene in one glioma. Our data have broadened the possible mutation spectrum of patients with Turcot's syndrome. The difference in the mutation spectrum of TGFBRII, BAX, and IGFIIR between brain and colorectal tumors in these individuals suggests that the mutator phenotype may target different pathogenic pathways in the oncogenic process of the two organs.

Adenomatous Polyposis Coli↗
PubMed1998

Prostaglandin, tumor necrosis factor alpha and neutrophils: causative relationship in indomethacin-induced stomach injuries.

Tumor necrosis factor alpha (TNF-alpha) has been suggested to play a critical role in indomethacin-induced gastric mucosal damage, so we evaluated its mucosal level and its relationship with prostaglandin E2 and neutrophils in indomethacin-induced gastric mucosal injury in rats. Indomethacin caused a time- and dose-dependent increase in gastric mucosal erosion, which was accompanied by a reduction in prostaglandin E2 followed by an increase in TNF-alpha level and neutrophil infiltration in the gastric mucosa. Pretreatment with exogenous prostaglandin E2 totally abolished indomethacin-induced gastric mucosal injury and the TNF-alpha increase. Depletion of neutrophils by methotrexate or reduction of TNF-alpha concentration by pentoxifylline markedly reduced indomethacin-induced mucosal damage. Pentoxifylline but not methotrexate prevented the increase in mucosal TNF-alpha level induced by indomethacin. It is suggested that depletion of prostaglandin E2 followed by an increase of TNF-alpha production and neutrophil infiltration in the gastric mucosa are important sequential processes in indomethacin-induced ulceration. Prevention of one of these processes would inhibit ulcer formation.

Animals↗
PubMed1998

Monocyte chemoattractant protein-1 (MCP-1) expression in primary lymphoepithelioma-like carcinomas (LELCs) of the lung.

Lymphoepithelioma-like carcinoma (LELC) of the lung is a recently recognized primary non-small cell lung carcinoma with distinct clinicopathological features and an aetiological association with Epstein-Barr virus (EBV) infection. The tumour consists of clusters and sheets of poorly or undifferentiated tumour cells in close association with numerous mononuclear inflammatory cells, including a rich component of tumour-associated macrophages (TAMs). To investigate the molecular mechanism leading to the TAM-rich stroma, the expression of a monocyte-specific chemotactic and activating factor, monocyte chemoattractant protein-1 (MCP-1), was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH), and the presence of TAMs was demonstrated by immunohistochemistry in nine LELCs. The results were compared with those found in 17 conventional non-small cell lung carcinomas. RT-PCR showed specific MCP-1 amplification in both LELCs and non-LELCs, but ISH demonstrated a unique and extensive expression of MCP-1 transcripts by the tumour cells of LELCs only, while TAMs, stromal fibroblasts, and endothelial cells formed the major source of MCP-1 in non-LELCs. TAMs in LELCs were more abundant and showed a close topographical relationship with the MCP-1-expressing tumour cells. The results indicate that tumour cell expression of MCP-1 in LELCs is an important mechanism contributing to their distinctive morphological features. This is the first study that demonstrates the in vivo upregulation of a monocyte-specific chemokine by EBV-related carcinomas, illustrating an interesting aspect of tumour biology in EBV-related neoplasms.

Adult↗
PubMed1998

Ultrasound diagnosis of fetal diaphragmatic hernia and complex congenital heart disease at 12 weeks' gestation--a case report.

Congenital diaphragmatic hernia is commonly associated with congenital heart disease. Their coexistence indicates a poor prognosis. Prenatal diagnosis of these conditions in early pregnancy allows the option of pregnancy termination. We present a case of left-sided fetal diaphragmatic hernia and complex congenital heart disease diagnosed by ultrasound examination at 12 weeks' gestation.

Abortion, Induced↗
PubMed1998

Microsatellite instability and mutation of DNA mismatch repair genes in gliomas.

Microsatellite instability (MSI) has been identified in various human cancers, particularly those associated with the hereditary nonpolyposis colorectal cancer syndrome. Although gliomas have been reported in a few hereditary nonpolyposis colorectal cancer syndrome kindred, data on the incidence of MSI in gliomas are conflicting, and the nature of the mismatch repair (MMR) defect is not known. We established the incidence of MSI and the underlying MMR gene mutation in 22 patients ages 45 years or less with sporadic high-grade gliomas (17 glioblastomas, 3 anaplastic astrocytomas, and 2 mixed gliomas, grade III). Using five microsatellite loci, four patients (18%) had high level MSI, with at least 40% unstable loci. Germline MMR gene mutation was detected in all four patients, with inactivation of the second allele of the corresponding MMR gene or loss of protein expression in the tumor tissue. Frameshift mutation in the mononucleotide tract of insulin-like growth factor type II receptor was found in one high-level MSI glioma, but none was found in the transforming growth factor beta type II receptor and the Bax genes. There was no family history of cancer in three of the patients, and although one patient did have a family history of colorectal carcinoma, the case did not satisfy the Amsterdam criteria for hereditary nonpolyposis colorectal cancer syndrome. Three patients developed metachronous colorectal adenocarcinomas, fitting the criteria of Turcot's syndrome. Thus, MSI and germline MMR gene mutation is present in a subset of young glioma patients, and these patients and their family members are at risk of developing other hereditary nonpolyposis colorectal cancer syndrome-related tumors, in particular colorectal carcinomas. These results have important implications in the genetic testing and management of young patients with glioma and their families.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Tissue-specific expression pattern of vascular endothelial growth factor isoforms in the malignant transformation of lung and colon.

Angiogenesis, a prerequisite for tumor growth and progression, results from a shift in the equilibrium between angiogenic factors and angiogenic inhibitors. Vascular endothelial growth factor (VEGF) has been identified as one of the most important factors mediating angiogenesis in physiological and pathological conditions. Through alternative splicing, four isoforms of VEGF are formed, consisting of 206, 189, 165, and 121 amino acids, respectively. VEGF206 and VEGF189 differ from VEGF165 and VEGF121 in their bioavailability, with the longer forms being matrix-bound and the shorter forms freely diffusible. To investigate the relative importance of the VEGF isoforms in neoplastic transformation, we studied the pattern of splice variant expression by reverse transcription polymerase chain reaction (RT-PCR) in 18 lung and 11 colonic carcinomas and their corresponding normal tissues, respectively. The findings showed a significant upregulation of VEGF in both carcinomas, with VEGF165 and VEGF121 being the predominant forms; VEGF189 was significantly expressed in normal lung but not colon; and VEGF206 was not detected in any specimen. The findings indicate that during malignant progression, an angiogenic switch favoring the shorter diffusible isoforms is likely to confer on the tumor a growth advantage. From the differential expression of VEGF isoforms in normal lung and colonic tissues, different functional roles of the splice variants is suggested. In particular, VEGF189 may be important for the maintenance of the vascular integrity of the lung.

Adenocarcinoma↗
PubMed1998

Expression of vascular endothelial growth factor in von Hippel-Lindau syndrome-associated papillary cystadenoma of the epididymis.

Vascular endothelial growth factor (VEGF) is a hypoxia inducible angiogenic and vascular permeability factor. Although VEGF expression in glioblastoma is induced by hypoxia, its expression in renal cell carcinoma and hemangioblastoma is thought to be related to mutation of the von Hippel-Lindau (VHL) gene. It is not certain whether other lesions in VHL syndrome are associated with an elevated VEGF level. We report a VHL syndrome patient with multiple hemangioblastomas and bilateral epididymal clear cell papillary cystadenomas. In situ hybridization revealed high levels of VEGF mRNA in the clear cells of the epididymal tumor and the stromal cells of the hemangioblastoma. This lends support to the notion that upregulation of VEGF is caused by loss of the wild-type VHL protein. We postulate that the elevated VEGF levels may account for the cyst formation and vascularized stroma present in these VHL-associated tumors.

Adult↗
PubMed1998

Fungal endocarditis in bone marrow transplantation: case report and review of literature.

We report a case of fungal endocarditis due to Aspergillus terreus in a leukaemia patient who received a bone marrow allograft from a matched unrelated donor. He presented with persistent fever. microangiopathic haemolytic anaemia but there was no cardiac signs and symptoms. He died despite intravenous amphotericin B. Review of the English literature showed five other patients with fungal endocarditis in the setting of bone marrow transplantation and revealed the same features of difficult diagnosis and poor outcome.

Adult↗
PubMed1998

Nonsteroidal antiinflammatory drugs could reverse Helicobacter pylori-induced apoptosis and proliferation in gastric epithelial cells.

It remains controversial whether the harmful effects of Helicobacter pylori (Hp) and nonsteroidal antiinflammatory drugs (NSAIDs) are additive. We studied the effects of Hp (virulent and nonvirulent strains) and NSAIDs, alone or in combination, on apoptosis and proliferation of gastric epithelial cells in nonulcer dyspepsia (NUD) patients. Forty-four (25 Hp-positive and 19 Hp-negative) consecutive Chinese NUD patients with rheumatoid arthritis who had taken continuously NSAIDs for more than three months were recruited for this study. Another 41 (20 Hp-positive and 21 Hp-negative) NUD patients not on any NSAIDs were included as controls. All patients underwent a gastroscopy examination and gastric biopsies. Hp infection was confirmed by CLOtest, anti-Hp ELISA, and [13C]urea breath test. The CagA status was determined by the anti-CagA antibody assay. The degree of gastritis, apoptosis, and proliferation indices were determined with H&E staining, terminal uridine deoxynucleotidyl nick end-labeling (TUNEL), and proliferating cell nuclear antigen (PCNA) immunostaining methods, respectively. A significantly higher apoptosis was observed in subjects who had Hp infection or had been consuming NSAIDs when compared with the controls. Unlike NSAID-treated subjects, patients with Hp infection were shown to have significantly enhanced cell proliferation. However, the increased apoptosis and proliferation in Hp-positive subjects were reversed by also taking NSAIDs. No correlation was found between apoptosis and proliferation in all the study groups. There was no association found between CagA expression or degree of gastritis with cell proliferation or apoptosis. It was demonstrated at the cellular level that NSAIDs could abrogate apoptosis or proliferation effects induced by Hp. Furthermore, the latter effects appeared not to be influenced by the virulent nature of the Hp strains.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Up-regulation of lysozyme production in colonic adenomas and adenocarcinomas.

AIMS: The presence of lysozyme protein in some gastric adenomas and adenocarcinomas has been well documented. There have been relatively few studies investigating the presence of lysozyme in tumours of the large intestine and they show contrasting results. We aim to investigate the cellular source and expression of lysozyme in colonic adenomas and adenocarcinomas. METHODS AND RESULTS: We randomly selected 29 and 27 colonic adenomas and adenocarcinomas, respectively. Using in-situ hybridization (ISH) and immunohistochemistry (IHC), we found an up-regulation of lysozyme in the dysplastic epithelium of all the adenomas studied, with more than 80% of cases expressing moderate to strong signals. Although the up-regulation of lysozyme was also observed in adenocarcinomas, only 30% of the cases showed moderate to strong signals, mostly with an uneven distribution. Down-regulation of lysozyme in the severely dysplastic and invasive foci were noted in some cases of adenoma with malignant transformation. Normal colonic glands were consistently negative for lysozyme at both the mRNA and the protein level, but inflamed and immature regenerative colonic epithelium at the crypt base showed positive signals in a similar pattern to those observed in the dysplastic epithelium of the adenomas. CONCLUSIONS: Our results confirm that colonic epithelium can produce lysozyme and its expression is up-regulated in the dysplastic epithelium in adenomas and in invasive cancer cells. It is interesting that regenerative colonic epithelium showed a similar pattern of lysozyme expression as in adenomas. The loss of lysozyme secreting phenotype in most of the invasive tumours suggests that lysozyme may not confer an advantage to tumour progression.

Adenocarcinoma↗
PubMed1998

Clearance of persistent hepatitis B virus infection in Chinese bone marrow transplant recipients whose donors were anti-hepatitis B core- and anti-hepatitis B surface antibody-positive.

Thirteen hepatitis B surface antigen-positive Chinese patients who received hepatitis B surface antibody-positive marrow (hepatitis B core antibody-positive or -negative: 6 and 7, respectively) via allogeneic bone marrow transplantation (BMT) were studied. After BMT, 4 recipients had serologic clearance of hepatitis B surface antigen from hepatitis B core antibody-positive marrow, but none of the recipients of hepatitis B core antibody-negative marrow had serologic clearance (P=.02). There was no significant difference in the donors' hepatitis B surface antibody titer before BMT for patients with or without serologic clearance of hepatitis B surface antigen (2255.2+/-4244.0 vs. 854.2+/-2306.7 mIU/mL; P=not significant). Adoptive immunity clearance of hepatitis B surface antigen was favored by hepatitis B core antibody positive-donor marrow and was not related to donor pre-BMT hepatitis B surface antibody titer.

Adolescent↗
PubMed1998

Expression of vascular endothelial growth factor and its receptors in the anaplastic progression of astrocytoma, oligodendroglioma, and ependymoma.

Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic factor, which is known to be upregulated in most cases of glioblastoma multiforme (GBM). The expression of VEGF and its receptors in ependymomas, oligodendrogliomas, and particularly the expression during anaplastic progression of these three types of gliomas has not been studied extensively. Fifty-six gliomas, consisting of 10 ependymomas, 12 oligodendrogliomas, 3 anaplastic oligodendrogliomas, 6 astrocytomas grade II, 5 anaplastic astrocytomas, and 20 glioblastoma multiformes, were investigated for VEGF and receptor expression using in situ hybridization (ISH) and reverse transcription polymerase chain reaction (RT-PCR). Results showed that VEGF was moderately to strongly expressed in 8 of 10 ependymomas and in all anaplastic oligodendrogliomas and glioblastoma multiforme cases. These tumors displayed similar degrees of extensive necrosis and vascular proliferation, with VEGF expression consistently seen in tumor cells around necrotic areas. The VEGF expression, although present at a lower level, also was shown in 4 of 12 oligodendrogliomas, in 3 of 6 astrocytomas grade II, and in 2 of 5 anaplastic astrocytomas, with a regional rather than diffuse pattern of positive result. The findings from the in situ hybridization study correlated with the expression index, as determined by reverse transcription polymerase chain reaction. Expression of VEGF was correlated significantly with vascular proliferation (p < 10(-5)) and necrosis (p < 10(-5)), as well as with microvessel density (p = 0.002, rs = 0.41). The VEGF receptors, kinase domain region (KDR) and Fms-like-tyrosine kinase (Flt-1), also were upregulated in the tumor vasculature of glioblastoma multiforme, anaplastic oligodendrogliomas, and ependymomas with necrosis, whereas the astrocytomas grade II, anaplastic astrocytomas, and oligodendroglioma tumors tended to express a weak to nondetectable signal. Anaplastic progression in all three types of gliomas is heralded by the occurrence of small zones of VEGF-expressing cells and early vascular proliferation, followed by an accelerated phase of angiogenesis closely associated with VEGF induction around areas of necrosis and with the expression of VEGF receptors in the tumor vasculature.

Astrocytoma↗
PubMed1998

Presence of Epstein-Barr virus in lymphoepithelioma-like carcinoma of the middle ear.

AIM: To examine the association of Epstein-Barr virus (EBV) with carcinoma of the ear. METHODS: Five non-keratinising squamous cell carcinomas and two undifferentiated carcinomas of the ear were examined. In situ hybridisation was used to localised EBV-encoded RNAs (EBER). Immunohistochemical methods to detect LMP-1 and EBNA2 were performed in the EBER positive cases. RESULTS: Two cases were EBER positive, including one non-keratinising and one undifferentiated carcinoma. Both showed identical morphology to those arising from the nasopharynx, with abundant lymphoid stroma. They were both negative for LMP-1 and EBNA2. CONCLUSIONS: EBV associated carcinoma with the morphology of lymphoepithelioma can also arise from the middle ear.

Adult↗
PubMed1998

p53 overexpression is different in Epstein-Barr virus-associated and Epstein-Barr virus-negative carcinoma.

AIMS: Epstein-Barr virus (EBV) is associated with a subset of gastric and head and neck carcinomas. While p53 mutation and overexpression is common in gastric cancer, in nasopharyngeal carcinoma p53 is overexpressed yet mutation is uncommon, leading to a proposed viral mechanism of p53 upregulation. We examined the expression of p53 protein in 18 EBV-associated gastric carcinomas (EBV-GA) and compared it with 29 age and sex matched EBV-negative gastric carcinomas (EBV0-GA) and 23 non-nasopharyngeal EBV-associated carcinomas (EBV-CAs) arising from various head and neck regions. METHODS AND RESULTS: Using two monoclonal antibodies (DO7 and PAb1801) with microwave pre-treatment, the p53 protein was scored according to the intensity and percentage of positive cells. The EBV0-GA showed a clear cut bimodal distribution of p53 levels, with either homogeneous intense staining of most tumour nuclei, or only very weak expression in a few cells. Nearly all the EBV-GA and EBV-CAs showed a weak to moderate p53 expression, characterized by heterogeneous intensity of staining in a variable proportion of tumour cells. CONCLUSIONS: The difference in p53 levels in the EBV0-GA and EBV-GA is statistically significant. The heterogeneous level of p53 in the EBV-GA and EBV-CAs and its difference from the EBV0-GA is suggestive of a non-mutational mechanism of p53 upregulation and underscores the role of the virus in the oncogenic pathway.

Carcinoma↗
PubMed1997

Prevalence of mutations and 30-bp deletion in the C-terminal region of Epstein-Barr virus latent membrane protein-1 oncogene in reactive lymphoid tissue and non-nasopharyngeal EBV-associated carcinomas in Hong Kong Chinese.

A specific variant of Epstein-Barr virus (EBV) with a 30-bp deletion in the C-terminal region of the LMP1 gene has been found in some EBV-associated malignancies. To better understand the tumorigenic role of this LMP1 variant, we used PCR and sequencing to examine the LMP1 gene in 38 EBV-associated carcinomas (EBV-CAs) occurring in various organs (6 lung, 10 salivary gland, 5 sino-nasal, 16 gastric and 1 metastatic NPC), 55 reactive lymphoid tissues from tonsils (TON) and 67 EBV-negative tumours in various organs (22 adenolymphoma of salivary gland, 14 gastric and 31 colonic adenocarcinomas), where the virus was demonstrated in lymphocytes. The TON showed prevalence of both deleted and non-deleted variants of LMP1, with dual infection being common. Significantly more of the LMP1 variant was deleted in EBV-CA and in EBV-negative tumours. Sequencing showed that the deleted and non-deleted variants have different sets of amino acid mutation. Mutations in codon 344 and 355 in the non-deleted variant disrupted the 9 nucleotide repeat flanking the deletion and thus may have conferred resistance to the deletion. The prevalence of both variants in the TON, with enrichment for the deleted variant in various organs, argues for the existence of an immune selection pressure in our population. The deleted variant, which may have a higher tumorigenic potential, may contribute to the high incidence of NPC, as well as the occurrence of EBV-CA in organs outside the nasopharynx in our locality.

Adolescent↗