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Biomedical subjects

T W Lam

Publications and source records attributed to T W Lam.

10 recordsLinked to original sources
PubMed2005

The mutated subsequence problem and locating conserved genes.

MOTIVATION: For the purpose of locating conserved genes in a whole genome scale, this paper proposes a new structural optimization problem called the Mutated Subsequence Problem, which gives consideration to possible mutations between two species (in the form of reversals and transpositions) when comparing the genomes. RESULTS: A practical algorithm called mutated subsequence algorithm (MSS) is devised to solve this optimization problem, and it has been evaluated using different pairs of human and mouse chromosomes, and different pairs of virus genomes of Baculoviridae. MSS is found to be effective and efficient; in particular, MSS can reveal >90% of the conserved genes of human and mouse that have been reported in the literature. When compared with existing softwares MUMmer and MaxMinCluster, MSS uncovers 14 and 7% more genes on average, respectively. Furthermore, this paper shows a hybrid approach to integrate MUMmer or MaxMinCluster with MSS, which has better performance and reliability.

Algorithms↗
PubMed2005

Efficient constrained multiple sequence alignment with performance guarantee.

The constrained multiple sequence alignment problem is to align a set of sequences of maximum length n subject to a given constrained sequence, which arises from some knowledge of the structure of the sequences. This paper presents new algorithms for this problem, which are more efficient in terms of time and space (memory) than the previous algorithms, and with a worst-case guarantee on the quality of the alignment. Saving the space requirement by a quadratic factor is particularly significant as the previous O(n4)-space algorithm has limited application due to its huge memory requirement. Experiments on real data sets confirm that our new algorithms show improvements in both alignment quality and resource requirements.

Algorithms↗
PubMed2004

Filtering of ineffective siRNAs and improved siRNA design tool.

MOTIVATION: Short interfering RNAs (siRNAs) can be used to suppress gene expression and possess many potential applications in therapy, but how to design an effective siRNA is still not clear. Based on the MPI (Max-Planck-Institute) basic principles, a number of siRNA design tools have been developed recently. The set of candidates reported by these tools is usually large and often contains ineffective siRNAs. In view of this, we initiate the study of filtering ineffective siRNAs. RESULTS: The contribution of this paper is 2-fold. First, we propose a fair scheme to compare existing design tools based on real data in the literature. Second, we attempt to improve the MPI principles and existing tools by an algorithm that can filter ineffective siRNAs. The algorithm is based on some new observations on the secondary structure, which we have verified by AI techniques (decision trees and support vector machines). We have tested our algorithm together with the MPI principles and the existing tools. The results show that our filtering algorithm is effective. AVAILABILITY: The siRNA design software tool can be found in the website http://www.cs.hku.hk/~sirna/ CONTACT: smyiu@cs.hku.hk

Algorithms↗
PubMed2004

An efficient algorithm for optimizing whole genome alignment with noise.

MOTIVATION: This paper is concerned with algorithms for aligning two whole genomes so as to identify regions that possibly contain conserved genes. Motivated by existing heuristic-based software tools, we initiate the study of an optimization problem that attempts to uncover conserved genes with a global concern. Another interesting feature in our formulation is the tolerance of noise, which also complicates the optimization problem. A brute-force approach takes time exponential in the noise level. RESULTS: We show how an insight into the optimization structure can lead to a drastic improvement in the time and space requirement [precisely, to O(k2n2) and O(k2n), respectively, where n is the size of the input and k is the noise level]. The reduced space requirement allows us to implement the new algorithm, called MaxMinCluster, on a PC. It is exciting to see that when tested with different real data sets, MaxMinCluster consistently uncovers a high percentage of conserved genes that have been published by GenBank. Its performance is indeed favorably compared to MUMmer (perhaps the most popular software tool for uncovering conserved genes in a whole-genome scale). AVAILABILITY: The source code is available from the website http://www.csis.hku.hk/~colly/maxmincluster/ detailed proof of the propositions can also be found there.

Algorithms↗
PubMed2004

Selective functional deficit in dendritic cell--T cell interaction is a crucial mechanism in chronic hepatitis B virus infection.

A defect in specific T cell immunity has long been assumed to be the central mechanism of persistent Hepatitis B virus (HBV) infection. Recent studies on HBV transgenic mice have suggested, however, that functional deficit of dendritic cells (DC) was an underlying cause for the T cell dysfunction. The functions of monocyte-derived DC were determined by studying 75 subjects that included chronic hepatitis B patients with low or high HBV load; antibody to hepatitis B surface antigen (anti-HBs) positive individuals who had recovered completely from previous acute HBV infection; healthy donors who had received hepatitis B vaccination and were anti-HBs positive; and immunologically naïve to HBV or the vaccine individual. Impaired interactions between monocyte-derived DC and T cells were shown in chronic HBV infection patients, especially in those with active virus replication. The dysfunctions included: (i) failure of DC to increase human leukocyte antigen (HLA-II), B7 expression and interleukin-12 secretion in responses to hepatitis B surface antigen (HBsAg), (ii) defective induction of T cell proliferative response to HBsAg, (iii) failure to activate T cells to produce cytokines and (iv) deficit in the induction of antigen specific cytotoxic T lymphocytes (CTLs). In vitro treatment of DC with tumour necrosis factor-alpha improved HLA-II and B7 expression, as well as Th cell and CTL responses. It is concluded that defective DC-T cell interactions may account for the specific T cell immune defects in chronic HBV infection. Immunotherapy that aims at restoring DC functions could offer a new opportunity for effectively managing persistent HBV infections.

Adult↗
PubMed2003

Rare pulmonary complications after transarterial chemoembolisation for hepatocellular carcinoma: two case reports.

We report two rare cases of acute pulmonary complication after transarterial chemoembolisation for inoperable hepatocellular carcinoma. Both cases involved a large tumour and hepatic vein invasion. The first patient, a 27-year-old man, died of pulmonary tumour embolism 4 days after transarterial chemoembolisation. Acute dyspnoea developed in the second patient, a 63-year-old man, following the procedure due to pulmonary oil embolisation and chemical pneumonitis. The chest condition of this patient improved, but he subsequently died of liver failure 3 weeks later. Our cases illustrate the point that if locoregional treatment is offered as a palliative treatment, patients with hepatic vein invasion should be warned of the possible complications of massive tumour embolism, pulmonary oil embolisation, and subsequent death.

Acute Disease↗
PubMed2000

A randomized clinical trial comparing autologous blood clot and gelfoam in transarterial chemoembolization for inoperable hepatocellular carcinoma.

BACKGROUND/AIM: Inoperable hepatocellular carcinoma is common in Asia and is usually treated with repeated transarterial chemoembolization. Gunji et al. showed better survival and fewer complications with autologous blood clot as compared with gelfoam used for embolization. Our aim was to compare the effect of blood clot versus gelfoam. METHODS: We conducted a prospective randomized trial in 100 patients with inoperable hepatocellular carcinoma, and compared the side effects and cumulative survival in the two groups. Cox's proportional hazard model was used to study the prognostic factors. RESULTS: The diameter of the main tumor was 7.9+/-4.6 cm. Our study did not show additional beneficial effects of blood clot. The proportion of side effects was similar and the common ones included fever, pain and vomiting. Though the hepatic artery remained patent for a longer period with blood clot (p=0.061), there was no difference in survival (p=0.129 for Okuda I disease and p=0.388 for Okuda II disease). Subgroup analysis showed longer survival in patients with vascular occlusion (p=0.034 for Okuda I and p=0.029 for Okuda II disease). The independent factors of survival were sex, Child's class, Okuda stage, tumor type and presence of metastases. CONCLUSION: This study showed no additional benefits of blood clot in patients with inoperable hepatocellular carcinoma, in Okuda I and II disease. The longer survival in patients with vascular occlusion suggested that the damage to normal liver tissue by planned periodic transarterial chemoembolization may outweigh its benefit in later sessions of repeated TACE in certain patients.

Aged↗
PubMed1995

Profile of opportunistic infections among HIV-1 infected people in Hong Kong.

BACKGROUND: To determine the spectrum of opportunistic infections in patients with human immunodeficiency virus (HIV-1) infection in Hong Kong. METHODS: A retrospective study of 214 HIV-1-infected patients, seen between December 1984 and December 1993 in a specialist clinic for HIV/AIDS: RESULTS: A majority (94%) of the patients in the cohort were male; 84% had acquired HIV via sexual contacts. Two-thirds were ethnic Chinese. Ninety-two (43%) had developed AIDS, and 54(25%) had presented with other non AIDS-defining opportunistic infections during the study period. The primary AIDS defining illnesses of 80 patients were infections: Pneumocystis carinii pneumonia (50%), extrapulmonary tuberculosis (10%) and cytomegalovirus (CMV) disease (8%). Opportunistic infections among Chinese and non-Chinese were similar in spectrum, though higher frequencies of infection with CMV, Mycobacterium avium intracellulare and tuberculosis were seen among Chinese, whereas the opposite was true for Pneumocystis carinii pneumonia, toxoplasmosis and cryptosporidiosis. Disseminated Penicillium marneffei infection was another significant disease for HIV-positive patients. Common non AIDS-defining opportunistic infections included herpes zoster, oral candidiasis, herpes simplex infection and genital/anal wart. The median CD4 count at HIV diagnosis for AIDS patients was much lower than non-AIDS patients (147 vs 546/ul). Survival of deceased AIDS patients was poor, with a median of only five months. Survival has however, apparently, improved over the recent years. CONCLUSIONS: In Hong Kong, Pneumocystis carinii pneumonia remained the most common primary AIDS event, while Penicillium marneffei was emerging as another significant cause of major infection. Herpes zoster and oral candidiasis were the two most frequently encountered minor opportunistic infections.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Percutaneous ethanol injection as a possible curative treatment for malignant portal vein thrombosis in hepatocellular carcinoma.

Postoperative residual hepatocellular carcinoma (HCC) with malignant portal vein thrombosis in a 48-year-old man was cured with transarterial chemoembolization (TACE) for the parenchymal portion and percutaneous ethanol injection (PEI) for the malignant portal vein thrombosis. No evidence of tumor recurrence was noted after 18 months of follow-up. The only severe complication in our patient was biliary stricture which was treated with an internal stent via endoscopic retrograde pancreatico-cholangiography (ERCP).

Carcinoma, Hepatocellular↗