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Biomedical subjects

P S Lee

Publications and source records attributed to P S Lee.

At least 19 recordsLinked to original sources
PubMed2004

Defining "occludable" angles in population surveys: drainage angle width, peripheral anterior synechiae, and glaucomatous optic neuropathy in east Asian people.

BACKGROUND: /aim: A current consensus in epidemiological studies of primary angle closure (PAC) is to diagnose the condition only if the posterior (usually pigmented) trabecular meshwork is seen for less than 90 degrees of the angle circumference, termed an "occludable angle." The authors sought to assess the validity of this epidemiological classification by exploring the relation between drainage angle width, peripheral anterior synechiae (PAS) and glaucomatous optic neuropathy (GON). METHODS: 918 Mongolians and 995 Chinese Singaporeans, both groups aged 40 years and older were examined in two population based surveys. Gonioscopic angle width was graded in five categories (0 = closed to 4 = wide open) according the scheme described by Shaffer. Cases with secondary PAS were excluded. RESULTS: The rate of PAS was between 0.3% and 1.7% in people with wide angles (grades 3 and 4). In those with grade 2 angles, PAS were seen in between 8% of eyes. In eyes with grade 1 angles, the rate rose to 17% in Chinese Singaporeans, and 31% in Mongolians. The odds of PAS were higher in people with narrower angles. However, there was a greater absolute number of people with PAS whose drainage angles were classified as "not occludable" than those classified "occludable." CONCLUSIONS: The traditional view that primary angle closure becomes a significant possibility in drainage angles of < or = grade 2 (approximately 20 degrees ) is valid in east Asians. The definition of an "occludable" angle examined here excludes many people with PAS. This probably serves to underemphasise the role of PAC in population surveys of glaucoma prevalence in Asian people.

Adult↗
PubMed2004

Ki-ras gene mutations, LOH of the APC and DCC genes, and microsatellite instability in primary colorectal carcinoma are not associated with micrometastases in pericolonic lymph nodes or with patients' survival.

AIMS: The primary aim of this study was to look for possible correlations between molecular genetic changes in primary colorectal cancer and the presence or absence of micrometastases in the accompanying pericolonic lymph nodes. The secondary aim was to correlate the data on these molecular genetic changes and micrometastases with survival. METHODS: One hundred and twenty five Dukes's stage B colorectal cancers from 1989 to 1992 were analysed. The primary tumours were evaluated for Ki-ras mutation, adenomatous polyposis coli (APC) loss of heterozygosity (LOH), deleted in colon cancer (DCC) LOH, and microsatellite instability using standard molecular techniques. All available lymph nodes were immunohistochemically stained for micrometastases. RESULTS: Micrometastases were present in 41% of patients. There were significantly more lymph nodes removed in the patients with micrometastases. Micrometastases were not associated with Ki-ras mutation, APC LOH, DCC LOH, or microsatellite instability, even when controlling for the number of lymph nodes removed. None of the molecular variables considered had a significant impact on either overall survival or on death with disease. CONCLUSIONS: There are insufficient data to justify using molecular genetic changes in primary colorectal carcinomas as prognostic markers. Micrometastases do not provide prognostic information on survival. There is value in increasing the numbers of lymph nodes removed and analysed along with the primary tumour.

Aged↗
PubMed2003

Prevalence of glaucoma in Thailand: a population based survey in Rom Klao District, Bangkok.

AIM: To determine prevalence, demography, mechanism, and visual morbidity of glaucoma in urban Thai people. METHODS: 790 subjects aged 50 years or older from Rom Klao district, Bangkok, Thailand, were enumerated in a population based cross sectional study. Each subject underwent the following investigations: visual acuity, visual field testing, slit lamp examination, applanation tonometry, gonioscopy, and an optic disc examination after mydriasis. Main outcome measures included visual acuity (logMAR), visual fields, intraocular pressure (IOP), gonioscopic characteristics, vertical cup/disc ratio (VCDR), prevalence of types of glaucoma. Glaucoma was diagnosed on the basis of optic disc appearance and visual field defects. In eyes in which the optic disc could not be examined, glaucoma was diagnosed when visual acuity was <3/60 and either IOP >99.5th percentile or there was evidence of previous glaucoma surgery. RESULTS: 701 subjects were examined (response rate 88.7%). In eyes with "normal" suprathreshold visual fields, the mean IOP was 13.3 mm Hg (97.5th percentile = 20 mm Hg). The 97.5th and 99.5th percentiles of VCDR were 0.72 and 0.86 respectively. Of the 701 subjects examined in the clinic, 27 had glaucoma (3.8%, 95% CI: 2.5 to 5.6), 16 had primary open angle glaucoma (POAG, prevalence 2.3%, 95% CI: 1.3 to 3.7), six were primary angle closure glaucoma (PACG, prevalence 0.9%, 95% CI: 0.3 to 1.9), and five were secondary glaucoma (SecG, prevalence 0.7%, 95% CI: 0.2 to 1.7). Among the 43 unilaterally blind subjects, glaucoma was the cause in five subjects (12%). One subject was bilaterally blind due to glaucoma (prevalence 11%, 95% CI: 0.3 to 61.9). 28 people (4%) were glaucoma suspects on the basis of optic disc appearance and six on the basis of visual fields only. 98 subjects (14%) had "occludable angles" in either eye, 22 of whom had primary angle closure (PAC, prevalence 3.1%, 95% CI: 1.9 to 4.7); 14 had peripheral anterior synechiae in either eye and eight had ocular hypertension (OHT). CONCLUSIONS: POAG accounted for 67% of all glaucoma, PACG 21%, and secondary glaucomas 12%. Glaucoma was the second most common cause of severe unilateral visual loss.

Age Distribution↗
PubMed2003

Case report: diabetic mastopathy.

Diabetic mastopathy is a source of confusion with breast carcinoma. The association between mastopathy and Type I diabetes of long duration has been reported, but this clinical condition is poorly recognized since breast examination is not routinely performed in young diabetic patients. Radiologists' awareness of the constellation of findings in diabetic mastopathy may spare patients from undergoing unwarranted surgical biopsies.

Adult↗
PubMed2002

Assessment of the genotoxic potential of ISIS 2302: a phosphorothioate oligodeoxynucleotide.

ISIS 2302, a phosphorothioate oligodeoxynucleotide with antisense activity against human ICAM-1 mRNA, was evaluated in a battery of tests to assess genotoxic potential. There was no evidence of genotoxicity in three in vitro studies performed: (i) a bacterial reverse mutation test; (ii) a chromosomal aberration test in Chinese hamster ovary cells; (iii) a mammalian cell gene mutation assay in L5187Y cells. Additionally, there was no in vivo evidence of genetic toxicity in a bone marrow micronucleus study in male and female mice. For all tests, top concentrations or doses assessed met harmonized regulatory guidelines. The cellular uptake of ISIS 2302 into target cells was confirmed using capillary gel electrophoresis and immunohistochemistry. Intracellular uptake into CHO cells, L5187Y cells, Salmonella typhimurium TA98 and bone marrow was concentration- and time-dependent. Consistent with what is known about the physical and chemical properties of phosphorothioate oligodeoxynucleotides, there was no evidence of genotoxicity in any of the assessed end-points. Furthermore, the absence of genotoxicity could not be ascribed to test system insensitivity or to an absence of exposure of the test system to ISIS 2302.

Animals↗
PubMed2001

Women's health issues in haemodialysis patients.

OBJECTIVES: To describe reproductive health issues in women with end-stage renal disease (ESRD) treated with haemodialysis. STUDY DESIGN: Cross-sectional survey based on structured interviews. SETTING: Nephrology units of two major metropolitan tertiary referral hospitals in Victoria and their satellite dialysis centres between 1 November 1998 to 30 June 1999. METHODS: Women aged 20 years or over in haemodialysis programs. OUTCOME MEASURES: Menstrual status; prevalence of menstrual and climacteric symptoms; use of gynaecological screening; and prevalence of comorbidities that may benefit from hormone replacment therapy. RESULTS: 48 women completed the survey. They were similar to the 485 women undergoing haemodialysis in Victoria in age (mean age, 55.5 years; range, 20-84 years), years on dialysis (mean age, 3.9 years; range, 1 month-17 years) and primary diagnosis. Eleven of the 15 premenopausal women reported menstrual cycles of 22-35 days, 13 reported common premenstrual symptoms, and six reported dysmenorrhoea that interfered with daily activities. Average age at menopause was 47.7 years (95% CI, 45.6-49.9 years), and six of the 31 postmenopausal women underwent menopause before 45 years. Eight had ever been prescribed hormone replacement therapy (oral in all cases). Over half the women (26) had not had a Pap smear in the last two years, and 12 of those aged over 50 (38%) had not had a mammogram in the same period. CONCLUSION: Despite their risk of early menopause, cardiovascular disease and bone fracture, few women undergoing haemodialysis were offered hormone replacement therapy. Nor were they adequately screened for gynaecological cancers. Women's health issues seem to be neglected among haemodialysis patients.

Adult↗
PubMed2001

Polyacene and cyclacene geometries and electronic structures: bond equalization, vanishing band gaps, and triplet ground states contrast with polyacetylene.

The ground-state geometries and excited singlet and lowest triplet energies of polyacenes from benzene through nonacene are predicted with B3LYP/6-31G* calculations and compared to experimental data where available. The results are compared to these data for cyclacenes and polyenes. The polyacenes and cyclacenes have geometries consisting of two fully delocalized nonalternating ribbons joined by relatively long bonds. Polyacenes are predicted to have smaller band gaps than the corresponding polyenes and triplet ground states for nine or more benzene rings. The fully delocalized nonalternating nature of polyacenes differs from the bond alternation resulting from Peierls distortion in polyenes. The differences are rationalized in terms of a simple MO model, and the results are compared to extensive prior theoretical work in the literature. Predictions about the electronic structure of analogues containing polyacene units are made.

Journal Article↗
PubMed2001

Genetic toxicology testing of the antimalarial drugs chloroquine and a new analog, AQ-13.

AQ-13 ([N1-(7-chloro-quinolin-4yl)-3-(N3,N3-diethylamino)propylamine] dihydrochloride trihydrate) is an aminoquinoline antimalarial drug that is effective against chloroquine-resistant strains of Plasmodium falciparum. It is structurally similar to the widely used chloroquine diphosphate (CQ). We evaluated these drugs in the three assays currently recommended by the International Conference on Harmonization (ICH): bacterial mutagenesis in Salmonella typhimurium and Escherichia coli, mammalian cell mutagenesis in L5178Y mouse lymphoma cells, and micronucleus induction in rat bone marrow. A small but statistically significant increase in revertant colonies was produced by CQ with Salmonella tester strain TA98 without metabolic activation (MA) and by AQ-13 with strain TA1537 both with and without MA. In L5178Y cells, testing of CQ and AQ-13 up to cytotoxic concentrations with and without MA produced no increase in mutant colonies and no increase in the numbers of small colonies. Slight decreases in the ratio of polychromatic erythrocytes (PCE) to red blood cells (RBC) were observed in male and female rats treated with CQ and in females only treated with AQ-13; however, none of these changes was statistically significant. No increases in the frequency of micronucleated PCE were observed at any dose level of CQ or AQ-13. Although both CQ and AQ-13 showed weak bacterial mutagenicity, this mutagenic effect was not confirmed in either the mouse lymphoma mutagenesis assay or the micronucleus assay. These results indicate that CQ and AQ-13 should pose minimal risk of genotoxic damage in human populations being administered these drugs.

Animals↗
PubMed2001

Protein tyrosine phosphatase phi regulates paxillin tyrosine phosphorylation and mediates colony-stimulating factor 1-induced morphological changes in macrophages.

Removal of colony-stimulating factor 1 (CSF-1) causes macrophages to round up and to increase their expression of protein tyrosine phosphatase phi (PTP phi). This is accompanied by the disruption of focal complexes and the formation of ruffles. Here we have overexpressed wild-type (WT) PTP phi and a phosphatase-inactive (C325S) mutant in a macrophage cell line in the presence and absence of CSF-1. In the presence of CSF-1, WT PTP phi induces cell rounding and ruffle formation, while C325S PTP phi has no effect. In contrast, in CSF-1-starved cells, C325S PTP phi behaves in a dominant negative fashion, preventing rounding and ruffling. Furthermore, C325S PTP phi increases adhesion in cycling cells, while WT PTP phi enhances motility. In WT PTP phi-overexpressing cells, the focal contact protein paxillin is selectively depleted from focal complexes and specifically dephosphorylated on tyrosine. In contrast, paxillin is hyperphosphorylated in C325S PTP phi-expressing cells. Moreover, a complex containing PTP phi, paxillin, and a paxillin-associated tyrosine kinase, Pyk2, can be immunoprecipitated from macrophage lysates, and the catalytic domain of PTP phi selectively binds paxillin and Pyk2 in vitro. Although PTP phi and Pyk2 do not colocalize with paxillin in focal complexes, all three proteins are colocalized in dorsal ruffles. The results suggest that paxillin is dephosphorylated by PTP phi in dorsal ruffles, using Pyk2 as a bridging molecule, resulting in a reduced pool of tyrosine-phosphorylated paxillin available for incorporation into focal complexes, thereby mediating CSF-1 regulation of macrophage morphology, adhesion, and motility.

Blotting, Western↗
PubMed2000

A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo.

Effective anti cancer strategies necessitate the use of agents that target tumor cells rather than normal tissues. In this study, we constructed a tumor-selective adenovirus, Delta24, that carries a 24-bp deletion in the E1A region responsible for binding Rb protein. Immunoprecipitation analyses verified that this deletion rendered Delta24 unable to bind the Rb protein. However, titration experiments in 293 cells demonstrated that the Delta24 adenovirus could replicate in and lyse cancer cells with great efficiency. Lysis of most human glioma cells was observed within 10 - 14 days after infection with Delta24 at 10 PFU/cell. In vivo, a single dose of the Delta24 virus induced a 66.3% inhibition (P<0.005) and multiple injections, an 83.8% inhibition (P<0.01) of tumor growth in nude mice. However, normal fibroblasts or cancer cells with restored Rb activity were resistant to the Delta24 adenovirus. These results suggest that the E1A-mutant Delta24 adenovirus may be clinically and therapeutically useful against gliomas and possibly other cancers with disrupted Rb pathway.

Adenoviridae↗
PubMed2000

Anterior chamber depth measurement as a screening tool for primary angle-closure glaucoma in an East Asian population.

OBJECTIVE: To evaluate anterior chamber depth measurement as a method of screening for primary angle-closure glaucoma in an East Asian population. DESIGN: Two-phase, cross-sectional, community-based study. SETTING: Rural and urban locations in the Hovsgol and Omnogobi provinces, Mongolia. PARTICIPANTS: Nine hundred forty-two (94.2%) of 1000 individuals in Hovsgol(1995) and 775 (96.9%) of 1000 individuals in Omnogobi (1997) aged 40 years or older were examined. MAIN OUTCOME MEASURES: Anterior chamber depth was measured by optical pachymetry, slitlamp-mounted A-mode ultrasound, and handheld ultrasound. Gonioscopy was used to detect occludable angles, defined as one in which the trabecular meshwork was visible for less than 90 degrees of angle circumference. Primary open-angle glaucoma was diagnosed in subjects with an occludable angle and glaucomatous optic neuropathy with visual morbidity. The area under the curve in a receiver operating characteristic plot was used to compare test performance. RESULTS: Optical pachymetry outperformed the slitlamp-mounted ultrasound method of anterior chamber depth measurement (area under the curve, 0.93 and 0.90, respectively; z test, P = .001). Handheld ultrasound (area under the curve, 0.86) was inferior to optical measurement (z test, P = .001) but did not differ significantly from slitlamp ultrasound (z test, P = .06). The optical method gave sensitivity of 85% and specificity of 84% at a screening cutoff of less than 2.22 mm for detecting occludable angles. CONCLUSIONS: Measurement of axial anterior chamber depth can detect occludable angles in this Asian population and therefore may have a role in population screening for primary angle-closure glaucoma.

Adult↗
PubMed2000

Genomic analysis.

Advances in genomic analysis include improved technology for DNA sequencing, routine use of DNA microarray technology for the analysis of gene expression profiles at the mRNA level and improved informatic tools to organize and analyze such data. At the same time, new developments in chip-based analysis of samples and the emergence of models of gene networks hold promise for the future of the 'Genomic Era'.

Animals↗
PubMed2000

Molecular evidence that the stromal and epithelial cells in pleomorphic adenomas of salivary gland arise from the same origin: clonal analysis using human androgen receptor gene (HUMARA) assay.

Salivary gland pleomorphic adenomas are characterized by a biphasic growth of "epithelial" and "stromal" regions. The "epithelial" region is a compactly organized mixture of both luminal and nonluminal cells, whereas the stromal region is composed predominantly of the nonluminal cells. Using the polymerase chain reaction (PCR)-based HUMARA assay on DNA from formalin-fixed, paraffin-embedded tissues from pleomorphic adnomas of female patients, we intend to clarify the clonal relation between the luminal and nonluminal cells and the clonal nature of the morphologically diverse nonluminal cells in this tumor. HUMARA, the human androgen receptor gene, is located on the X chromosome and contains a segment of polymorphic CAG tandem repeats in exon 1. Several methylation-sensitive HhaI restriction sites are located 5' to these CAG repeats. It is an ideal tool to study clonality of female tissues by examining the methylation pattern. Of the 13 cases analyzed, 3 were homozygous at the HUMARA locus and therefore noninformative. The remaining 10 cases were informative. All 10 cases showed a monoclonal pattern in the stromal area, indicating that the morphologically diverse nonluminal cells are monoclonal. Eight of the 10 cases showed monoclonality in the "epithelial" areas, suggesting a common clonality between luminal and nonluminal cells. Of the remaining 2 samples, 1 was polyclonal for the "epithelial" region, and the other was not amplifiable. Our data provide the first molecular evidence that the luminal and nonluminal cells in pleomorphic adenomas arise from the same clone in most cases, and the morphologically diverse nonluminal cells are monoclonal.

Adenoma, Pleomorphic↗
PubMed2000

Detection of gonioscopically occludable angles and primary angle closure glaucoma by estimation of limbal chamber depth in Asians: modified grading scheme.

AIM: To evaluate the performance of limbal chamber depth estimation as a means of detecting occludable drainage angles and primary angle closure, with or without glaucoma, in an east Asian population, and determine whether an augmented grading scheme would enhance test performance. METHOD: A two phase, cross sectional, community based study was conducted on rural and urban areas of Hövsgöl and Omnögobi provinces, Mongolia. 1800 subjects aged 40 to 93 years were selected and 1717 (95%) of these were examined. Depth of the anterior chamber at the temporal limbus was graded as a percentage fraction of peripheral corneal thickness. An "occludable" angle was one in which the trabecular meshwork was seen in less than 90 degrees of the angle circumference by gonioscopy. Primary angle closure (PAC) was diagnosed in subjects with an occludable angle and either raised pressure or peripheral anterior synechiae. PAC with glaucoma (PACG) was diagnosed in cases with an occludable angle combined with glaucomatous optic neuropathy and consistent visual morbidity. RESULTS: Occludable angles were identified in 140 subjects, 28 of these had PACG. The 15% grade (equivalent to the traditional "grade 1") yielded sensitivity and specificity of 84% and 86% respectively for the detection of occludable angles. The 5% grade gave sensitivity of 91% and specificity of 93% for the detection of PACG. The interobserver agreement for this augmented grading scheme was good (weighted kappa 0.76). CONCLUSIONS: The traditional limbal chamber depth grading scheme offers good performance for detecting occludable drainage angles in this population. The augmented scheme gives enhanced performance in detection of established PACG. The augmented scheme has potential for good interobserver agreement.

Adult↗
PubMed1999

The Cbl protooncoprotein stimulates CSF-1 receptor multiubiquitination and endocytosis, and attenuates macrophage proliferation.

Colony-stimulating factor-1 (CSF-1) activation of the CSF-1 receptor (CSF-1R) causes Cbl protooncoprotein tyrosine phosphorylation, Cbl-CSF-1R association and their simultaneous multiubiquitination at the plasma membrane. The CSF-1R is then rapidly internalized and degraded, whereas Cbl is deubiquitinated in the cytoplasm without being degraded. We have used primary macrophages from gene-targeted mice to study the role of Cbl. Cbl-/- macrophages form denser colonies and, at limiting CSF-1 concentrations, proliferate faster than Cbl+/+ macrophages. Their CSF-1Rs fail to exhibit multiubiquitination and a second wave of tyrosine phosphorylation previously suggested to be involved in preparation of the CSF-1-CSF-1R complex for endocytosis. Consistent with this result, Cbl-/- macrophage cell surface CSF-1-CSF-1R complexes are internalized more slowly, yet are still lysosomally degraded, and the CSF-1 utilization by Cbl-/- macrophages is reduced approximately 2-fold. Thus, attenuation of proliferation by Cbl is associated with its positive regulation of the coordinated multiubiquitination and endocytosis of the activated CSF-1R, and a reduction in the time that the CSF-1R signals from the cell surface. The results provide a paradigm for studies of the mechanisms underlying Cbl attenuation of proliferative responses induced by ligation of receptor tyrosine kinases.

Animals↗
PubMed1999

Retinal manifestations of HIV-1 and HIV-2 infections among hospital patients in The Gambia, west Africa.

BACKGROUND: In developed countries, 50-75% of AIDS patients develop retinal complications and about 20-40% acquire cytomegalavirus (CMV) retinitis. We conducted a cross-sectional survey to determine prevalence of these in The Gambia where both HIV-1 and HIV-2 infection are present and the prevalence of HIV-1 is rising. METHOD: All patients attending hospital whose percentage CD4+ cells (CD4%) was below 14, the level associated typically with an AIDS diagnosis, and one half of those whose CD4% was 14 or above were asked to join the study. Fifty-six HIV-1, 52 HIV-2 and 12 dually infected patients were recruited. Photographs of the fundi were taken and interpreted independently. The findings were related to the patients' percentage CD4+ cells. RESULTS: The CD4% was < 14 in 40 patients and < 7 in 17 patients. Thirty-six patients were male. No cases of CMV retinitis were found. Four patients whose CD4% were 4, 5, 11 and 23 had cotton wool spots ranging in number from 1 to 14 for any one patient. The prevalence of cotton wool spots was 8% (95% CI, 0-16%) among patients with CD4% below 14 and 12% (95% CI, 0-27) among patients with CD4% below 7. One of the 4 patients had associated microaneurysm and blot haemorrhages typical of more advanced HIV microvasculopathy. CONCLUSION: CMV retinitis is less common in The Gambia than in developed countries. Non-infectious retinopathy may also be less common.

AIDS-Related Opportunistic Infections↗
PubMed1999

Effects of blood glucose levels on performance in activities of daily living: a case example of a diabetic man with an acquired brain injury.

Dysfunctional blood glucose regulation and sequelae of acquired brain injury (ABI) can affect behavioural training in brain injury rehabilitation. The relationship is examined between blood glucose levels and performance in three activities of daily living (ADL) skills (showering, toileting, and dressing) in a 21-year-old male with ABI and Type I diabetes mellitus. Multiple daily glucometer readings were obtained both pre- and post-treatment. Skills training involved graduated prompting and reinforcement to develop independence in ADLs. Assessment and teaching occurred initially in hospital, and then was presented at home. Results show a strong negative relationship between daily fluctuations in blood glucose levels and performance; no relationship was found between daily mean levels and performance. Implications for treatment approaches for diabetic individuals with ABI are discussed.

Activities of Daily Living↗