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Biomedical subjects

S K Lam

Publications and source records attributed to S K Lam.

At least 91 records · Page 5Linked to original sources
PubMed2001

Non-steroidal anti-inflammatory drugs induce apoptosis in gastric cancer cells through up-regulation of bax and bak.

Aspirin- and non-steroidal anti-inflammatory drug (NSAID)-induced apoptosis is one of the important mechanisms for their anti-tumour effect in gastric cancer. We aimed at determining the role of bcl-2 family proteins and caspases in the apoptotic process. Gastric cancer cell lines AGS (wild-type p53) and MKN-28 (mutant p53) were used. Cell proliferation was measured by MTT assay. Apoptosis was determined by acridine orange staining. Protein expressions were determined by western blotting. Aspirin and indomethacin inhibited cell proliferation and induced apoptosis in both cells. AGS cells were more sensitive compared with MKN-28 cells. The pro-apoptotic proteins bax and bak were overexpressed after treatment, while the protein level of bcl-2 remained unchanged. Apoptosis was accompanied by an increase in caspase-3 activity and cleavage of caspase-3 and poly(ADP-ribose) polymerase. Inhibition of caspase-3 rescued aspirin-induced apoptosis. Our results suggest that one of the major pathways which mediates the anti-tumour response of aspirin and indomethacin in gastric cancer cells is through up-regulation of bax and bak and activation of caspase-3. Bax and bak are important in the chemoprevention of gastric cancer.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Comparison of the complete nucleotide sequences of echovirus 7 strain UMMC and the prototype (Wallace) strain demonstrates significant genetic drift over time.

The complete nucleotide sequences are reported of two strains of echovirus 7, the prototype Wallace strain (Eo7-Wallace) and a recent Malaysian strain isolated from the cerebrospinal fluid of a child with fatal encephalomyelitis (Eo7-UMMC strain). The molecular findings corroborate the serological placement of the UMMC strain as echovirus 7. Both Eo7-Wallace and Eo7-UMMC belong to the species human enterovirus B and are most closely related to echovirus 11. Eo7-UMMC has undergone significant genetic drift from the prototype strain in the 47 years that separate the isolation of the two viruses. Phylogenetic analysis revealed that Eo7-UMMC did not arise from recombination with another enterovirus serotype. The molecular basis for the severely neurovirulent phenotype of Eo7-UMMC remains unknown. However, it is shown that mutations in the nucleotide sequence of the 5' untranslated region (UTR) of Eo7-UMMC result in changes to the putative structure of the 5' UTR. It is possible that these changes contribute to the neurovirulence of Eo7-UMMC.

3' Untranslated Regions↗
PubMed2001

Complete nucleotide sequences of Nipah virus isolates from Malaysia.

We have completely sequenced the genomes of two Nipah virus (NiV) isolates, one from the throat secretion and the other from the cerebrospinal fluid (CSF) of the sole surviving encephalitic patient with positive CSF virus isolation in Malaysia. The two genomes have 18246 nucleotides each and differ by only 4 nucleotides. The NiV genome is 12 nucleotides longer than the Hendra virus (HeV) genome and both genomes have identical leader and trailer sequence lengths and hexamer-phasing positions for all their genes. Both NiV and HeV are also very closely related with respect to their genomic end sequences, gene start and stop signals, P gene-editing signals and deduced amino acid sequences of nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, glycoprotein and RNA polymerase. The existing evidence demonstrates a clear need for the creation of a new genus within the subfamily Paramyxovirinae to accommodate the close similarities between NiV and HeV and their significant differences from other members of the subfamily.

Base Sequence↗
PubMed2001

Synchronous gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma in association with Helicobacter pylori infection: comparing reported cases between the East and West.

The association of Helicobacter pylori infection with synchronous gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma is rare. Three Chinese patients (M:F = 1:2) who were 71, 58, and 75 yr of age were diagnosed to have gastric adenocarcinoma (2 patients) and gastric lymphoma (1 patient) on endoscopic biopsies. Distal gastrectomy was performed in all of them. Histological study of the three resected specimens revealed synchronous gastric adenocarcinoma and MALT lymphoma. H. pylori infection was found in two patients. A literature search revealed another 29 patients with synchronous tumors in whom H. pylori status was examined. Overall, H. pylori infection was found in 78% of 32 patients. The majority of lymphoma was low grade (75%) and was larger than carcinoma (81%). The majority of carcinoma (65.6%) was early. This suggested lymphoma might develop before carcinoma or the presence of MALT lymphoma might increase the risk of developing carcinoma.

Adenocarcinoma↗
PubMed2001

Soluble E-cadherin is a valid prognostic marker in gastric carcinoma.

BACKGROUND: Gastric cancer remains a major cause of cancer mortality globally but no good prognostic tumour marker is available. Soluble fragment of E-cadherin protein has been reported to increase in the sera of patients with cancer and recently was found to be elevated in 67% of patients with gastric cancer. AIMS: To investigate if serum soluble E-cadherin is a valid prognostic marker in gastric cancer. METHODS: Concentrations of soluble E-cadherin from 116 patients with histologically confirmed gastric adenocarcinoma and 40 healthy subjects were measured using an immunoenzymometric method with a commercially available sandwich ELISA kit based on monoclonal antibodies. RESULTS: The logarithm of the means of soluble E-cadherin concentration was significantly higher in patients with gastric cancers (mean 3.85 (SD 0.28)) than in healthy subjects (3.71 (0.18)) (p=0.001), and in palliative/conservatively treated cancers (3.91 (0.35)) than in operable cancers (3.78 (0.19)) (p=0.015). The logarithm of the concentrations correlated with tumour size (p=0.032) and carcinoembryonic antigen concentrations (p=0.001). The cut off value calculated from discriminant analysis on operability and inoperability/palliative treatment was 7025 ng/ml. Soluble E-cadherin concentrations higher than this cut off value predicted tumour (T4) depth invasion (p=0.020, confidence interval (CI) 1.008-1.668) and palliative/conservative treatment (p=0.023, CI 1.038-2.514). In contrast, the relative risks for lymph node (N2) metastasis, distant metastasis, and stage III/IV disease were 1.41, 1.33, and 1.55 respectively, despite not reaching statistical significance. CONCLUSION: Serum soluble E-cadherin is a potential valid prognostic marker for gastric cancer. A high concentration predicts palliative/conservative treatment and T4 invasion.

Adenocarcinoma↗
PubMed2001

Protective role of heme oxygenase-1 on trinitrobenzene sulfonic acid-induced colitis in rats.

Preliminary studies showed that the inducible form of heme oxygenase (HO-1) was induced and played a protective role in the process of inflammation. The present study investigated the possible role of HO-1 in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. We measured HO-1 activity in TNBS-induced colitis in rats and analyzed the severity of colitis along with altered HO activity by assessing lesion area and myeloperoxidase activity. HO-1 mRNA and protein expressions were determined at different time points after TNBS induction. Free radical production and inducible nitric oxide synthase (iNOS), which participate in oxidative injury, were also assayed. HO activity and HO-1 gene expression increased markedly after TNBS induction. Administration with tin mesoporphyrin (SnMP), a HO inhibitor, potentiated the colonic damage along with a reduction in HO-1 activity. Furthermore, the reduction of HO-1 expression by SnMP also enhanced reactive oxygen species and iNOS expression, both of which were dramatically increased after the TNBS enema. L-Arginine pretreatment further aggravated the injurious action of SnMP. Our results indicate that HO-1 plays a protective role in the colonic damage induced by the TNBS enema, and the preventive effects probably result from decreased free radical production and inhibition of iNOS expression in colonic tissues.

Animals↗
PubMed2001

Gastric cancer: past, present and future.

Gastric cancer remains a major cause of cancer mortality in the world. However, in the past 10 decades, the view of gastric cancer has been changing. This includes the unexplained decline in the incidence of the cancer, the proximal shift of the cancer in the stomach, the identification of Helicobacter pylori as an etiological agent, rapid development in molecular tumour biology, new treatment modalities and the adoption of mass screening for prevention. This article reviews the changing views of gastric cancer and the latest developments.

Adult↗
PubMed2001

Helicobacter pylori infection--current treatment practice.

Helicobacter pylori infection, which is present in 30 - 60% of the population in developed countries and in more than 60% in developing countries, is established to be a major cause of gastritis, peptic ulcer disease and gastric cancer. Eradication therapy has been incorporated into clinical practice over the past 15 years. Treatment regimens include a 2 week bismuth-based triple therapy (a bismuth compound plus metronidazole, tetracycline or amoxycillin), a 1 week proton-pump inhibitor (PPI)-based triple therapy and a 1 week ranitidine bismuth citrate (RBC)-based triple therapy (a PPI or RBC plus any two of the three antibiotics, metronidazole, amoxycillin and clarithromycin). These regimens achieve eradication rates of >> 80%. H. pylori resistance to metronidazole and clarithromycin decreases the clinical efficacy of most regimens, despite the high eradication rates for resistant strains achieved by the RBC-triple therapy in some recent trials. The dose of antibiotics (especially clarithromycin) and the duration of treatment may also influence the eradication rate. Doctors' beliefs impact on clinical practice and, thus, influence the clinical application of eradication therapy. Whereas peptic ulcer disease and primary gastric low-grade B-cell mucosa-associated lymphoid tissue lymphoma (MALToma) have become established as definite indications for eradication therapy, there remain controversies surrounding non-ulcer dyspepsia, gastro-oesophageal reflux disease, atrophic gastritis, intestinal metaplasia, use of non-steroidal anti-inflammatory drugs (NSAIDs) and H. pylori-related extradigestive diseases.

Aged↗
PubMed2001

Emerging viral diseases of Southeast Asia and the Western Pacific.

Over the past 6 years, a number of zoonotic and vectorborne viral diseases have emerged in Southeast Asia and the Western Pacific. Vectorborne disease agents discussed in this article include Japanese encephalitis, Barmah Forest, Ross River, and Chikungunya viruses. However, most emerging viruses have been zoonotic, with fruit bats, including flying fox species as the probable wildlife hosts, and these will be discussed as well. The first of these disease agents to emerge was Hendra virus, formerly called equine morbillivirus. This was followed by outbreaks caused by a rabies-related virus, Australian bat lyssavirus, and a virus associated with porcine stillbirths and malformations, Menangle virus. Nipah virus caused an outbreak of fatal pneumonia in pigs and encephalitis in humans in the Malay Peninsula. Most recently, Tioman virus has been isolated from flying foxes, but it has not yet been associated with animal or human disease. Of nonzoonotic viruses, the most important regionally have been enterovirus 71 and HIV.

Animals↗
PubMed2001

Chikungunya infection--an emerging disease in Malaysia.

Many countries neighboring Malaysia have reported human infections by chikungunya virus, a mosquito-borne togavirus belonging to the genus Alphavirus. However, although there is serological evidence of its presence in Malaysia, chikungunya virus has not been known to be associated with clinical illness in the country. An outbreak of chikungunya virus occurred in Klang, Malaysia, between December 1998 and February 1999. The majority of the cases were in adults and the clinical presentation was similar to classical chikungunya infections. Malaysia is heavily dependent on migrant workers from countries where chikungunya is endemic. It is speculated that the virus has been re-introduced into the country through the movement of these workers.

Alphavirus Infections↗
PubMed2001

Serological evidence of hantavirus infections in Malaysia.

Hantaviruses are primarily rodent-borne and transmission is by inhalation of virus-contaminated aerosols of rodent excreta, especially urine and saliva. The genus Hantavirus, family Bunyaviridae, comprises at least 14 serotypes and the symptoms of clinical illness range from mild fever to severe hemorrhagic manifestations with renal complications. Many countries in Southeast Asia are unaware of the importance of hantavirus infections and give them low priority. Malaysia, like other countries in the region, has conducted very few studies on the epidemiology of hantaviruses - and even these were conducted in the 1980s. Using a more extensive range of hantavirus antigens, we conducted a seroprevalence study of rodents and humans and found further evidence of hantavirus infections. Moreover, the data from the antibody profiles strongly suggest the presence of different hantaviruses at the study sites.

Animals↗
PubMed2000

Nipah virus: a recently emergent deadly paramyxovirus.

A paramyxovirus virus termed Nipah virus has been identified as the etiologic agent of an outbreak of severe encephalitis in people with close contact exposure to pigs in Malaysia and Singapore. The outbreak was first noted in late September 1998 and by mid-June 1999, more than 265 encephalitis cases, including 105 deaths, had been reported in Malaysia, and 11 cases of encephalitis or respiratory illness with one death had been reported in Singapore. Electron microscopic, serologic, and genetic studies indicate that this virus belongs to the family Paramyxoviridae and is most closely related to the recently discovered Hendra virus. We suggest that these two viruses are representative of a new genus within the family Paramyxoviridae. Like Hendra virus, Nipah virus is unusual among the paramyxoviruses in its ability to infect and cause potentially fatal disease in a number of host species, including humans.

Animals↗
PubMed2000

Clinical features of Nipah virus encephalitis among pig farmers in Malaysia.

BACKGROUND: Between September 1998 and June 1999, there was an outbreak of severe viral encephalitis due to Nipah virus, a newly discovered paramyxovirus, in Malaysia. METHODS: We studied the clinical features of the patients with Nipah virus encephalitis who were admitted to a medical center in Kuala Lumpur. The case definition was based on epidemiologic, clinical, cerebrospinal fluid, and neuroimaging findings. RESULTS: Ninety-four patients with Nipah virus infection were seen from February to June 1999 (mean age, 37 years; ratio of male patients to female patients, 4.5 to 1). Ninety-three percent had had direct contact with pigs, usually in the two weeks before the onset of illness, suggesting that there was direct viral transmission from pigs to humans and a short incubation period. The main presenting features were fever, headache, dizziness, and vomiting. Fifty-two patients (55 percent) had a reduced level of consciousness and prominent brain-stem dysfunction. Distinctive clinical signs included segmental myoclonus, areflexia and hypotonia, hypertension, and tachycardia and thus suggest the involvement of the brain stem and the upper cervical spinal cord. The initial cerebrospinal fluid findings were abnormal in 75 percent of patients. Antibodies against Hendra virus were detected in serum or cerebrospinal fluid in 76 percent of 83 patients tested. Thirty patients (32 percent) died after rapid deterioration in their condition. An abnormal doll's-eye reflex and tachycardia were factors associated with a poor prognosis. Death was probably due to severe brain-stem involvement. Neurologic relapse occurred after initially mild disease in three patients. Fifty patients (53 percent) recovered fully, and 14 (15 percent) had persistent neurologic deficits. CONCLUSIONS: Nipah virus causes a severe, rapidly progressive encephalitis with a high mortality rate and features that suggest involvement of the brain stem. The infection is associated with recent contact with pigs.

Adult↗
PubMed2000

Early detection of hepatocellular carcinoma increases the chance of treatment: Hong Kong experience.

The prognosis for patients with hepatocellular carcinoma (HCC) is poor because of the low chance of curative treatment. To increase the chance of intervention and to improve survival, early detection of subclinical HCC (SCHCC) by alpha-fetoprotein (AFP) and/or ultrasonography (USG) screening is implemented in many countries. Three hundred six Chinese patients with HCC diagnosed between January 1995 and December 1997 were recruited. They were categorized into two groups: 142 patients (group 1) had SCHCC diagnosed by screening (AFP and/or USG), and 164 patients (group 2) presented with symptomatic HCC. The tumor size was significantly smaller in group 1 compared with that of group 2 (3.5 cm vs. 8.1 cm; P <.0001). A significantly higher proportion of patients had bilobar involvement, multifocal HCC, diffuse-type HCC, portal vein infiltration, and distant metastasis in group 2 when compared with group 1. Operability and feasibility of treatment by transcatheter intra-arterial chemoembolization (TACE) in group 1 patients (26.8% and 45.1%, respectively) were significantly better than in group 2 patients (7.9% and 32.3%, P <.0001 and P =.03, respectively). The cumulative survival rate was significantly higher in group 1 than in group 2 (P <.0001). For those who had surgical resection and those who had TACE, group 1 patients had a higher cumulative survival rate compared with that of group 2 patients (P =.04 and P =.0003, respectively). Screening for HCC by AFP and/or USG can identify tumors at an early stage, resulting in a higher chance of receiving treatment. Whether it can improve survival requires a further prospective, randomized study.

Adult↗
PubMed2000

Regulation of interleukin 6 production in a human gastric epithelial cell line MKN-28.

Interleukin (IL-) 6 is closely related to gastrointestinal diseases. The question of whether gastric epithelial cell contributes to IL-6 production remains undefined. We aim to evaluate the regulatory pathway of IL-6 expression in gastric epithelial cells, by using different inflammatory cytokines, endotoxin, or protein kinase modulators. IL-6 was measured by ELISA. Phorbol-12-myristate-13-acetate (PMA), calcium ionophore A23187, TNF-alpha, IL-1beta, oncostatin M (OSM) but not lipopolysaccharide stimulated IL-6 production from gastric epithelial cell line MKN-28. Blocking protein tyrosine kinase (PTK) activation by herbimycin A or genistein, or blocking NF-kappaB activation by pyrrolidinedithiocarbamate, reduced the IL-6 expression induced by TNF-alpha, IL-1beta and OSM. Dexamethasone mimicked this effect. Protein kinase (PK) C inhibitor only reduced the PMA and OSM induced IL-6 production. Both inhibitors and activators for PKA and G-protein as well as IL-10 had no effects on IL-6 expression. These results indicate that inflammatory cytokines are crucial for IL-6 regulation in gastric epithelial cells. The IL-6 signal pathway is mediated through PTK, NF-kappaB, and also involve PKC, intracellular calcium and sensitive to dexamethasone, but is not related to PKA, G-protein and IL-10.

Cell Survival↗