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Biomedical subjects

W R Lee

Publications and source records attributed to W R Lee.

At least 19 recordsLinked to original sources
PubMed2006

No association of cytokine gene polymorphisms in Chinese patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common chronically relapsing skin disease associated with the activation of T-helper 2 cells. Recent studies have shown that polymorphisms in the genes for interleukin (IL)-4, the IL-4 receptor, IL-13, and signal transducer and activator 6 (STAT6) may contribute to susceptibility of AD. To date, no cytokine gene polymorphism study has been conducted on Chinese patients with AD. AIMS: To determine whether genetic polymorphisms of the cytokine genes might influence the development of AD. METHODS: DNA samples were obtained from 94 patients and 186 control subjects. Using direct sequencing and microsatellite genotyping, we examined 22 polymorphisms in eight cytokine genes including the genes for IL-4, -10, -12B and -13, the IL-4 receptor, tumour necrosis factor (TNF)-alpha, STAT6, and interferon (IFN)-gamma. RESULTS: No significantly different allelic and genotypic distributions of the cytokine gene polymorphisms could be found between patients and controls. Moreover, no association was observed with disease onset, gender, the presence of elevated serum total IgE level or blood eosinophilia. CONCLUSION: Our study suggests that the analysed genetic polymorphisms of cytokine genes do not appear to be associated with AD susceptibility in our Chinese population.

Adolescent↗
PubMed2005

Type 1 Stickler syndrome: a histological and ultrastructural study of an untreated globe.

AIMS: To present a histological and ultrastructural study of an untreated globe in a patient with genetically confirmed type 1 Stickler syndrome. METHODS: Histological and electron microscopic examinations were performed on the enucleated globe from the proband of a pedigree with type 1 Stickler syndrome. Linkage analysis was carried out using polymorphic markers flanking the COL2A1 gene and the mutation was identified by direct sequencing. RESULTS: The significant retinal abnormality was incarceration of vitreous collagen within glial strands on the inner surface of an atrophic and gliotic detached retina. The incarcerated collagenous layers contained glial cells and extended from the retina to form strands, some of which contributed to a retrolental membrane. Mutation screening detected a C to T mutation in exon 47 that inserted a premature termination codon into the reading frame of the mRNA. Sequence analysis of three of the four affected children confirmed that they were also heterozygous for the base change. The youngest child's DNA was not analysed. CONCLUSIONS: The study represents the first evidence of abnormal interactions between pathological vitreous collagen and the inner retina in a patient with type 1 Stickler syndrome with a confirmed mutation in the COL2A1 gene.

Adult↗
PubMed2005

Plasmacellular differentiation in extranodal marginal zone B cell lymphomas of the ocular adnexa: an analysis of the neoplastic plasma cell phenotype and its prognostic significance in 136 cases.

AIM: To determine (a) the expression of plasma cell related antigens in extranodal marginal zone B cell lymphomas (EMZL) of the ocular adnexa; and (b) the prognostic value of plasmacellular differentiation in these tumours. METHODS: A consecutive case series of 136 ocular adnexal EMZL obtained from three ocular pathology centres over 20 years was analysed retrospectively. An extensive immunohistochemical panel, including the plasma cell related antigens VS38c, CD38, CD138, multiple myeloma oncogene-1-protein (MUM1/IRF4), and CREB binding protein (CBP) was performed. EMZL were defined as "plasmacellular differentiated" on the basis of morphological features, evidence of cytoplasmic immunoglobulin, negativity for BSAP/PAX5, and expression of at least one of the investigated plasma cell related antigens. Controls included normal or hyperplastic lymphatic tissues. Detailed clinical data were collected for most patients, and compared with the results of immunohistochemistry. The end points considered for statistical analysis were development of local tumour recurrence, development of systemic disease, and lymphoma related death. RESULTS: 57 (42%) of the 136 ocular adnexal EMZL showed a plasmacellular differentiation; 45 of these plasmacytoid cases were primary tumours. In contrast with most admixed normal plasma cells, which displayed co-expression of MUM1/IRF4, Vs38c, CD38, CD138, and CBP, the plasmacellular differentiated EMZL tumour cells demonstrated co-expression of all five plasma cell related antigens in only six of 57 (11%) plasmacellular differentiated ocular adnexal EMZL. The most commonly expressed plasma cell related antigen was MUM1/IRF4, immunoreactivity being seen in 56/57 (98%) plasmacellular differentiated EMZL examined. Although the association of plasmacellular differentiation in primary ocular adnexal EMZL and disseminated disease was statistically significant on univariate analysis (p = 0.042), this was weaker on multivariate analysis. CONCLUSION: Plasmacellular differentiated tumour cells in EMZL demonstrate an aberrant immune profile for plasma cell related antigens when compared with normal plasma cells. On multivariate analysis, plasmacellular differentiation in ocular adnexal EMZL was not significantly associated with local recurrence, the development of systemic disease, or with lymphoma related death.

ADP-ribosyl Cyclase↗
PubMed2004

Improved survival rates in sebaceous carcinoma of the eyelid.

PURPOSE: To review the clinicopathological features, management, and survival rates for patients with sebaceous gland carcinoma of the eyelid, and to analyse the reasons for improved survival. METHODS: In the west of Scotland between 1975 and 2001, 32 cases were identified through the pathology index for sebaceous carcinoma. Pathology specimens were reviewed in all cases. The clinical data were obtained from hospital records and the database provided by the Regional Cancer Registry. RESULTS: A total of 22 female and 10 male patients were identified. Follow-up ranged from 6 months to 15 years, median of 4.8 years. Primary treatment involved excisional techniques in 27 cases, exenteration in two cases, enucleation in two cases, and two cases required adjuvant radiotherapy. Intraepithelial spread and masquerade presentations delayed the diagnosis. Poorly differentiated tumours were associated with an unfavourable outcome. Three patients developed local tumour recurrence and one metastatic disease. In all, 10 patients died from nontumour-related causes and one died from metastatic sebaceous carcinoma. The overall tumour mortality rate in the west of Scotland was 3%. CONCLUSIONS: From this study, patients in the west of Scotland have a better prognosis than is indicated in the literature. Astute clinical suspicion and accurate histopathological diagnosis, together with radical and aggressive surgical approaches were key factors.

Adenocarcinoma, Sebaceous↗
PubMed2003

Histological and morphometric analysis of the effects of argon laser epilation.

AIM: To analyse the location and extent of tissue damage induced after argon laser epilation. METHODS: Laser burns were applied to the lid margins of four patients before excision for entropion ("live tissue") and the lid margin of one patient was lasered after an excision for ectropion ("dead tissue"). The laser burns were directed towards the lash follicle and between 10 and 50 burns were applied with an argon blue-green laser set at power 0.9-1.0 W, at 0.1-0.2 second duration and a 100 micro m spot size. The tissues were processed for conventional histology. Serial sections were obtained and used for area measurements and three dimensional reconstructions of the burns to determine the volume and location of tissue destruction. RESULTS: The laser created a cone-shaped region of tissue ablation with surrounding coagulative necroses. Maximum burn depth was 1.2 mm in dead tissue and 0.8 mm in live tissue. Maximum necrosis depth was 1.4 mm in dead tissue and 0.9 mm in live tissue. Follicle depth ranged from 0.8 mm to 1.9 mm. Some of the burns had been misdirected in the dermis leaving target hair follicles intact, despite being of adequate depth. CONCLUSIONS: The argon laser has some potential for ablation of lash follicles, but accurate placement of the burn is essential and energy levels greater than those currently recommended should be applied. The treatment is ineffective in patients unable to remain immobile.

Aged↗
PubMed2001

A prospective quality-of-life study in men with clinically localized prostate carcinoma treated with radical prostatectomy, external beam radiotherapy, or interstitial brachytherapy.

PURPOSE: To prospectively assess the health-related quality of life (HRQOL) and changes in HRQOL during the first year after 3 different treatments for clinically localized prostate cancer. METHODS AND MATERIALS: Ninety men with T1-T2 adenocarcinoma of the prostate were treated with curative intent between May 1998 and June 1999 and completed a quality-of-life Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire before treatment (T0) and 1 month (T1), 3 months (T3), and 12 months (T12) after treatment. Forty-four men were treated with permanent source interstitial brachytherapy (IB), 23 received external beam radiotherapy (EBRT), and 23 men were treated with radical prostatectomy (RP). The mean age of the entire study population was 65.9 years (median 67, range 42-79). The mean pretreatment prostate-specific antigen level of the entire study population was 6.81 ng/mL (median 6.25, range 1.33-19.6). The Gleason score was <or=6 in 65 (72%) of 90. The repeated measures analysis of variance and analysis of covariance were conducted on all quality-of-life and urinary outcome measures. RESULTS: A comparison of the demographic characteristics of the 3 treatment groups demonstrated significant differences. The men treated with RP were significantly younger than the men in either the IB or EBRT group (median age 61.0 RP, 67.1 IB, 68.8 EBRT; p = 0.0006). The men in the IB group were more likely to have a Gleason score of <or=6 than the EBRT group (Gleason score <or=6, 86% IB and 48% EBRT; p = 0.015). The mean score (standard deviation) at T0, T1, T3, and T12 for the FACT-P questionnaire for each group was as follows: IB 138.4 (17.0), 120.5 (21.7), 130.0 (18.4), and 138.5 (14.2); EBRT 137.1 (12.1), 129.5 (21.0), 134.4 (19.2), and 136.9 (15.6); and RP 138.3 (14.7), 117.7 (18.3), 134.4 (17.8), and 140.4 (14.9), respectively. Statistically significant differences over time were observed for the FACT-P in the IB and RP groups (p <0.0001), but not for the EBRT group (p = 0.08). The examination of the subscales within the FACT-P instrument demonstrated statistically significant changes over time in the IB and RP groups for the following: physical well-being, functional well-being, and prostate cancer symptoms. After adjusting for age, race, T stage, Gleason score, use of hormonal therapy, and baseline FACT-P scores, statistically significant differences in the FACT-P score at T1 according to treatment group were observed. At T12, the FACT-P scores were not significantly different than the baseline FACT-P scores for any group. CONCLUSIONS: The results of this analysis suggest that significant decreases in HRQOL, as measured by the FACT-P instrument, are evident in the first month after IB or RP, but not after EBRT. One year after treatment, however, the FACT-P scores were not statistically different from the baseline measures for any group. For all treatment groups, most of the HRQOL decreases were observed in the physical, functional, and prostate cancer-specific domains. These results suggest that the HRQOL changes are likely to be treatment-specific, further emphasizing the importance of a randomized trial comparing the different treatment options in this population of men.

Adult↗
PubMed2001

Transdermal drug delivery enhanced and controlled by erbium:YAG laser: a comparative study of lipophilic and hydrophilic drugs.

The influence of an erbium:YAG laser on the transdermal delivery of drugs across skin was studied in vitro. Indomethacin and nalbuphine, which have the same molecular weight, were selected as model lipophilic and hydrophilic drugs, respectively, to compare skin permeation by laser treatment. The results indicate a significant increase in the permeation of indomethacin and nalbuphine across skin pretreated with an erbium:YAG laser. The laser had a greater effect on the permeation of hydrophilic molecules which usually possess low permeability. The laser intensity and its spot size were found to play an important role in controlling transdermal delivery of drugs. Permeation of the hydrophilic drug increased following an increase of laser energy. On the other hand, a different result was observed for the lipophilic drug transported across laser-treated skin. The stratum corneum (SC) layer in skin could be partly ablated by the erbium:YAG laser. The barrier function of the SC may also be modulated by a lower intensity of the laser without affecting the viability and structure of the epidermis/dermis as determined by histological observations. However, ultrastructural alteration of the epidermis/dermis may be caused by laser treatment. Use of an erbium:YAG laser is a good method for enhancing transdermal absorption of both lipophilic and hydrophilic drugs, because it allows precise control of SC removal, and this ablation of SC can be reversible to the original normal status.

Administration, Cutaneous↗
PubMed2001

Usefulness of diabetic retinopathy as a marker of risk for thallium myocardial perfusion defects in non-insulin-dependent diabetes mellitus.

Among 236 non-insulin-dependent diabetics with clinically suspected coronary artery disease, the rate of thallium-201 myocardial perfusion defects was significantly higher in subjects with (40.6%) than without (22.1%) diabetic retinopathy. Retinopathy was associated with a higher risk of perfusion defects in subjects with cardiac and noncardiac chest pain, and may thus be a useful marker for selecting patients in whom thallium scintigraphy screening is warranted.

Chi-Square Distribution↗
PubMed2001

Effect of mutagen-induced cell lethality on the dose response of germline mutations.

Molecular tests for mutations require a sample of tissue from which DNA is extracted, to determine the presence or absence of one or more mutations per sample. To ensure mutation fixation each sample must consist of an equal number of cells that have had one or more DNA replications. In an in vivo test, surviving stem cells compensate to give the same number of cells per sample, leaving as the only evidence for stem cell lethality the increase in mutants of clonal origin because the mutant clone developed from a population of fewer stem cells. A problem is that an increase in mutagen dose increases stem cell death, resulting in a decreased number of surviving target cells, thus giving a downward bias of samples with one or more mutations per sample. To compare in vivo tests with molecular tests we will use as a model system the sex-linked recessive lethal (SLRL) test for germ cell mutations in Drosophila melanogaster. Spermatogonia cells in male larvae were exposed to ENU and mutations detected in sperm cells from adults. The same SLRL data were analyzed by two methods: (1) The conventional analysis of SLRL data, in which each mutation of a cluster of mutations of common origin was counted. (2) An analysis was used to simulate a sample for molecular analysis by determining mutations per male with an equal size sample of progeny per male. With this second analysis a correction factor is required based on the change in cluster size of mutants of common origin.

Animals↗
PubMed2001

Inhibition of nitric oxide synthase inhibitors and lipopolysaccharide induced inducible NOS and cyclooxygenase-2 gene expressions by rutin, quercetin, and quercetin pentaacetate in RAW 264.7 macrophages.

Several natural flavonoids have been demonstrated to perform some beneficial biological activities, however, higher-effective concentrations and poor-absorptive efficacy in body of flavonoids blocked their practical applications. In the present study, we provided evidences to demonstrate that flavonoids rutin, quercetin, and its acetylated product quercetin pentaacetate were able to be used with nitric oxide synthase (NOS) inhibitors (N-nitro-L-arginine (NLA) or N-nitro-L-arginine methyl ester (L-NAME)) in treatment of lipopolysaccharide (LPS) induced nitric oxide (NO) and prostaglandin E2 (PGE2) productions, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) gene expressions in a mouse macrophage cell line (RAW 264.7). The results showed that rutin, quercetin, and quercetin pentaacetate-inhibited LPS-induced NO production in a concentration-dependent manner without obvious cytotoxic effect on cells by MTT assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide as an indicator. Decrease of NO production by flavonoids was consistent with the inhibition on LPS-induced iNOS gene expression by western blotting. However, these compounds were unable to block iNOS enzyme activity by direct and indirect measurement on iNOS enzyme activity. Quercetin pentaacetate showed the obvious inhibition on LPS-induced PGE2 production and COX-2 gene expression and the inhibition was not result of suppression on COX-2 enzyme activity. Previous study demonstrated that decrease of NO production by L-arginine analogs effectively stimulated LPS-induced iNOS gene expression, and proposed that stimulatory effects on iNOS protein by NOS inhibitors might be harmful in treating sepsis. In this study, NLA or L-NAME treatment stimulated significantly on LPS-induced iNOS (but not COX-2) protein in RAW 264.7 cells which was inhibited by these three compounds. Quercetin pentaacetate, but not quercetin and rutin, showed the strong inhibitory activity on PGE2 production and COX-2 protein expression in NLA/LPS or L-NAME/LPS co-treated RAW 264.7 cells. These results indicated that combinatorial treatment of L-arginine analogs and flavonoid derivates, such as quercetin pentaacetate, effectively inhibited LPS-induced NO and PGE2 productions, at the same time, inhibited enhanced expressions of iNOS and COX-2 genes.

Animals↗
PubMed2001

Alternative activation of extracellular signal-regulated protein kinases in curcumin and arsenite-induced HSP70 gene expression in human colorectal carcinoma cells.

We have investigated the regulation mechanism of chemical stress-induced HSP70 gene expression in human colorectal carcinoma cells (COLO205 and HT29). Our data show that chemical treatments including sodium arsenite and curcumin, induced significant synthesis of HSP70 and its mRNA. The induced HSP70 gene expression appears to be increased at the transcriptional level. The increase in HSP70 gene expression by both chemicals is associated with an increase in HSF binding to HSE and induction of HSF1 di- or trimerization. Phosphorylation and activation of extracellular signal-regulated proteins (ERK1/2) were detected in sodium arsenite-treated COLO205 and HT29 cells, and the free radical scavenger N-acetyl-L-cysteine (NAC) was able to inhibit this ERK1/2 activation and HSP70 gene expression. MAPK blockade by the specific MEK1 inhibitor (PD98059) decreased the ability of sodium arsenite to increase HSP70 gene expression in a dose-dependent manner along with dephosphorylation of ERK1/2 proteins. In contrast to arsenite treatment, activation of ERK1/2 was not detected in curcumin-treated colorectal carcinoma cells, and NAC and PD98059 did not show any inhibitory effect on HSP70 gene expression induced by curcumin. Overexpression of a dominant negative mutant of mitogen-activated protein kinase kinase kinase 1 (MEKK1-DN) prevents arsenite-induced ERK1/2 phosphorylation and HSP70 protein synthesis. These results indicated that the ERK signaling pathway can participate in HSP70 gene expression induced by the prooxidant sodium arsenite, but not by the antioxidant curcumin.

Acetylcysteine↗
PubMed2001

A window on the current status of diabetes mellitus in Singapore--the Diabcare-Singapore 1998 study.

The Diabcare-Singapore project was carried out in 22 clinics (general hospitals, GH and primary healthcare centres, PHC) to provide an overview of diabetes management and metabolic control status. Data from 1697 diabetic patients were collected on paper forms and analysed centrally. Type 2 diabetes mellitus patients constituted 91.4% and type I patients constituted 8.1% of population. The proportion of type I patients was greater in GH (18.1%) vs PHC (3.4%). The mean age (+/- SD) was 58.1 +/- 14.4 years and mean duration of diabetes was 10.1 +/- 7.5 years. Mean body mass index (BMI) was 25.1 +/- 4.4 kg/m2 and more than half (53%) of patients were overweight (BMI >25 kg/m2). Mean HbA1c and FBG levels were 8.0 (1.9% and 9.1 +/- 3.1 mmol/l. A total of 51% of patients had HbA1c (1% above the Upper Limits of Normal (ULN). Fasting blood glucose (FBG) was >7.8 mmol/l in 61% of patients. The majority (70%) had satisfactory levels of fasting lipids (triglycerides, total cholesterol and HDL-cholesterol). Only 19.7% practised home blood glucose self-monitoring, while 99% reported receiving some diabetes education. Sixteen percent of patients had abnormal levels of protein (>500 mg/24 h) in the urine, 3% had elevated serum creatinine levels and 36% had microalbuminuria. Retinopathy (12%), cataract (16%) and neuropathy (12%) were commonly reported diabetic complications. The data revealed suboptimal glycaemic control in about half of patients studied.

Adolescent↗