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Biomedical subjects

W C Lee

Publications and source records attributed to W C Lee.

At least 109 records · Page 6Linked to original sources

Properties of the geometrically averaged ratio, an alternative standardized measure.

In epidemiology, the comparative mortality figure and the standardized mortality ratio are standardized measures in common use. Both are weighted averages of rate ratios (or observed/expected death count ratios) on the arithmetic scale. I propose a new standardized measure, the geometrically averaged ratio (GAR), which is defined through simple averaging on the logarithmic scale. I show that, in addition to providing a valid comparison between populations, the geometrically averaged ratio possesses the following desirable properties: (1) invertibility and invariance of standardized sex ratios and (2) interpopulational comparability with different standards.

Epidemiologic Methods↗

Serum uric acid levels in patients with cirrhosis: a reevaluation.

It has been reported that the serum uric acid levels in patients with cirrhosis were decreased compared with healthy subjects. These studies suggested that the lower serum uric acid levels in cirrhotic patients were attributed mainly to an increased effective vascular volume, and consequently to an excessive renal clearance of uric acid. However, the previous observations are challenged by a recent hypothesis for the pathogenesis of hyperdynamic circulation and formation of ascites in cirrhosis. The current study was undertaken to reevaluate serum uric acid levels in patients with cirrhosis. Ninety-eight cirrhotic patients with normal renal functions were included in this study. All biochemical and hemodynamic data were utilized for analysis. The mean serum uric acid level (mean, 6.1+/-1.2 mg/dL; range, 2.7-9.1 mg/dL) was higher than that of the age- and sex-matched healthy control subjects (mean, 5.5+/-1.3 mg/dL; range, 2.9-8.1 mg/dL; p = 0.018). Using multiple regression analysis it was determined that the serum uric acid level was not related to the severity of liver disease, cardiac index, systemic vascular resistance, and hepatic venous pressure gradient but was related closely to age (r = 0.210, p = 0.026) and effective renal plasma flow (r = -0.677, p < 0.0001). Compared with cirrhotic patients without ascites, those with ascites had a significantly higher serum uric acid level (6.7+/-1.6 mg/dL vs. 5.6+/-1.7 mg/dL, p < 0.05) and lower effective renal plasma flow (396+/-125 mL/min vs. 445+/-149 mL/min, p < 0.05). In conclusion, for cirrhotic patients with normal serum creatinine levels, the current study shows that the mean serum uric acid level is higher than that of healthy control subjects. It is not related to the severity of liver failure and systemic and portal hemodynamics, but is related closely to renal functions, especially the renal plasma flow.

Adult↗

Crystallization and preliminary crystallographic analysis of major nitroreductase from Escherichia coli.

NADPH:nitrocompound oxidoreductase from Escherichia coli, NfsA, has been crystallized in the presence of FMN by the vapor-diffusion method using polyethylene glycol 6000 as a precipitant. The crystals belonged to the triclinic space group P1 with cell dimensions, a = 52.2, b = 52.7, c = 53.3 A, alpha = 75.1, beta = 60.1, gamma = 60.5 degrees. The crystals are expected to contain two NfsA molecules per asymmetric unit. The crystals diffracted X-rays to at least 2.3 A resolution and are appropriate for structural analysis at high resolution.

Crystallization↗

Effects of octreotide on central hemodynamics and systemic oxygen use in patients with viral cirrhosis.

OBJECTIVE: Octreotide has potentially beneficial effects in patients with cirrhosis. However, the effects of octreotide on central hemodynamics and oxygen use have not been established. The present study was undertaken to evaluate the effect of octreotide on central hemodynamics and oxygen use in patients with viral cirrhosis. METHODS: Twenty-five patients with cirrhosis were enrolled in the study. They were randomly assigned to receive either placebo (n = 10) or a continuous infusion of 100 microg/h of octreotide after an initial 100-microg bolus (n = 15). Hemodynamic measurements and oxygenation values were obtained before and 60 min after octreotide or placebo administration. RESULTS: Placebo administration did not have any effect on hemodynamic and oxygenation values. In patients who received octreotide, systemic hemodynamic values including cardiac index, mean arterial pressure, and systemic vascular resistance were not affected. The mean pulmonary arterial pressure tended to increase after octreotide administration but was statistically insignificant. There was a significant increase in pulmonary arterial vascular resistance, whereas the pulmonary capillary wedge pressure and right atrial pressure were significantly decreased. Arterial oxygen tension, systemic oxygen uptake, and oxygen extraction ratio were significantly decreased after octreotide administration, whereas oxygen transport as well as arterial and mixed venous oxygen contents remained unchanged. CONCLUSIONS: In patients with viral cirrhosis, octreotide administration exerted a significant effect on pulmonary circulation. It also resulted in a decrease in systemic oxygen uptake and oxygen extraction ratio. These results suggested that octreotide may impair tissue oxygenation in patients with viral cirrhosis.

Aged↗

Frequent mutations of NF2 and allelic loss from chromosome band 22q12 in malignant mesothelioma: evidence for a two-hit mechanism of NF2 inactivation.

We previously reported NF2 mutations in malignant mesothelioma (MM) cell lines and corresponding primary tumors. We have now generated polyclonal antibodies that specifically recognize the C-terminus of the NF2 protein. Western blot analysis was performed on 25 MM cell lines, 14 of which showed no NF2 expression. Single-strand conformation polymorphism and DNA sequence analyses revealed NF2 mutations in each of these 14 cell lines. To explore the mechanism of inactivation of NF2, loss of heterozygosity analysis was performed with two microsatellite markers located in the vicinity of the NF2 locus in chromosome band 22q12. Eighteen of the 25 cell lines (72%) showed losses at one or both loci tested. All cases exhibiting mutation and/or aberrant expression of NF2 showed allelic losses, suggesting that inactivation of NF2 in MM occurs via a two-hit mechanism.

Blotting, Western↗

Mercury concentrations in scalp hair as an environmental contamination index from foods in Korea.

Relationships have been established between the mercury (Hg) levels in human scalp hair and environmental or dietary mercury exposures. The average value of total mercury (THg) in scalp hair of male residents in Seoul city was 1.66 +/- 1.10 ppm (+/- SD) and for methylmercury (MeHg) was 1.02 +/- 0.72 ppm (61% of total Hg). For females, THg was 1.06 +/- 0.46 ppm and MeHg was 0.51 +/- 0.27 ppm (48.8% of total Hg). The levels of Hg in scalp hair of male subjects were significantly different according to their occupations and age groups, but in females such variation was not detectable. The Hg levels in fishing village residents were significantly higher than those of Seoul residents. The concentrations of both THg and MeHg of residents in Korean fishing villages were similar to those of residents in fishing villages of other countries. Correlation between THg and MeHg contents in scalp hair was statistically highly significant.

Adolescent↗

The p16 status of tumor cell lines identifies small molecule inhibitors specific for cyclin-dependent kinase 4.

Loss of p16 functional activity leading to disruption of the p16/cyclin-dependent kinase (CDK) 4:cyclin D/retinoblastoma pathway is the most common event in human tumorigenesis, suggesting that compounds with CDK4 kinase inhibitory activity may be useful to regulate cancer cell growth. To identify such inhibitors, the 60 cancer cell lines of the National Cancer Institute drug screen panel were examined for p16 alterations (biallelic deletion, intragenic mutations, or absent p16 protein), and the growth-inhibitory activity of more than 50,000 compounds against these 60 cell lines was compared with their p16 status. One compound, 3-amino thioacridone (3-ATA; NSC 680434), whose growth-inhibitory activity correlated with the p16 status of the cell lines had an IC50 of 3.1 microM in a CDK4 kinase assay. In addition, four compounds structurally related to 3-ATA inhibited CDK4 kinase with IC50s ranging from 0.2-2.0 microM. All five of these compounds were less potent inhibitors of cell division cycle 2 and CDK2 kinases, with IC50s 30- to 500-fold higher than that for CDK4. ATP competition experiments demonstrated a noncompetitive mode of inhibition for 3-ATA (K(i) = 5.5 microM) and a linear mixed mode for benzothiadiazine (NSC 645787; K(i) = 0.73 microM). We have successfully demonstrated a novel approach to identify specific CDK4 kinase inhibitors that may selectively induce growth inhibition of p16-altered tumors.

Antineoplastic Agents↗

Somatic genetic alterations in human malignant mesothelioma (review).

A review of cytogenetic and molecular genetic findings in human malignant mesotheliomas (MMs) is presented. The complex profile of somatic genetic changes characteristic of MMs implicates a multistep process of tumorigenesis in this malignancy. In particular, the occurrence of multiple, recurrent cytogenetic deletions in MMs suggests that loss and/or inactivation of tumor suppressor genes (TSGs) are critical to the development and progression of such tumors. Karyotypic and comparative genomic hybridization analyses of MMs have demonstrated frequent deletions of specific regions within chromosome arms 1p, 3p, 6q, 9p, 15q and 22q, and subsequent loss of heterozygosity (LOH) studies have documented high frequencies of allelic loss from each of these chromosomal sites. Positional candidate gene approaches have identified TSGs within two of these regions, i.e., p16/CDKN2A at 9p21 and NF2 at 22q12, which are frequently altered in MMs. Homozygous deletions appear to be the major mechanism affecting p16/CDKN2A, whereas inactivating mutations coupled with allelic loss occur at the NF2 locus. High density LOH analyses have pinpointed minimal regions of deletion in 1p, 3p, 6q, and 15q and are expected to facilitate efforts to identify putative TSGs at these locations which contribute to the pathogenesis of MMs.

Chromosome Aberrations↗

Phenotype, function, and in vivo migration and survival of allogeneic dendritic cell progenitors genetically engineered to express TGF-beta.

BACKGROUND: Administration of donor bone marrow (BM)-derived dendritic cell (DC) progenitors (DCp) that are major histocompatibility complex (MHC) class II+ but costimulatory molecule (CD40, CD80, CD86)-deficient can prolong mouse heart allograft survival This is associated with microchimerism and inhibition of antidonor cytotoxic T lymphocyte (CTL) activity. Genetic modification of these donor antigen-presenting cells to express an immunosuppressive molecule(s) may enhance their in vivo survival and potential tolerogenicity. METHODS: The surface phenotype of B10(H-2b) DCp before and after gene transfer using replication-deficient adenoviral (Ad) vectors was determined by monoclonal antibody (mAb) staining and flow cytometry. Transforming growth factor-beta (TGF-beta) production was quantitated by enzyme-linked immunosorbent assay. Allostimulatory activity of the gene-transduced DCp was ascertained by mixed leukocyte reaction (MLR) and CTL induction. To assess their in vivo migratory activity and survival, the transduced cells were injected subcutaneously into one hind footpad of C3H (H-2k) mice. Tissues (draining popliteal lymph nodes [LN], spleens, and thymi) were removed 1, 2, 7, and 14 days later and stained for donor MHC class II using anti-LA(b) mAb in an immunohistochemical procedure. The mean number of IAb+ cells per unit area was determined. RESULTS: Transduction with a control Ad vector (Ad-LacZ) at 50 multiplicity of infection slightly increased CD40 and CD86 expression and up-regulated the poor allostimulatory activity of the DCp assessed by MLR and CTL responses. These effects on function were negated in Ad-TGF-beta1-transduced cells. After their injection into mouse footpads, the gene-transduced IAb+ cells were observed in maximal numbers in the popliteal LN at day 1 and in marginal zones and T-dependent areas of spleens (peak at day 7) but were rare in thymi. Transduction with Ad-LacZ reduced the numbers of IAb+ cells identified in both LN and spleens at all time points postinjection, suggesting that the vector alone affected DC life span in allogeneic recipients. TGF-beta1 transgene expression not only fully prevented the reduction in DC induced by Ad transduction alone, but also increased numbers and prolonged the survival of donor cells in the spleen, as shown by a two-to fivefold increase in IAb+ cells at days 2-14 compared with control (Ad-LacZ-transduced) DC. CONCLUSION: BM-derived DCp can be transduced efficiently to express TGF-beta1 using an Ad vector. They exhibit very poor allostimulatory activity and similar migration characteristics in vivo to unmodified DCp. Survival of TGF-beta gene-transduced DC, however, is enhanced significantly compared with unmodified and (especially) control Ad-LacZ gene-transduced DC. Genetic engineering of donor DC to express the immunosuppressive molecule TGF-beta promotes their survival in allogeneic hosts and may potentiate their previously reported tolerogenicity.

Adenoviridae↗

Impacted aural foreign body requiring endaural incision and canal widening for removal.

Foreign bodies of the ear are a common finding in children. The majority of these can be removed relatively easily. We present a case which required endaural incision and widening of the external meatus before the foreign body could be successfully removed. Entrapment of the hard, oval-shaped, smooth and slippery foreign body deep to the hour-glass narrowing of the external canal, proximity of the object to the tympanic membrane and localised tissue oedema were the indications for the surgery. This case demonstrates the danger of unskillful attempts to remove aural foreign bodies.

Child↗

The association of cigarette smoking and alcohol consumption with other cardiovascular risk factors in men from Seoul, Korea.

PURPOSE: To explore the effects of cigarette smoking and alcohol consumption on cardiovascular disease risk factors such as hypertension, dyslipidemia, and glucose intolerance in Korean men. METHODS: In this cross-sectional study, we gathered the smoking and drinking history by self-administered questionnaire between June 1994 and May 1995 among 1053 men, age 20-77, who visited a prevention center for a multiphasic health check at St. Mary's Hospital, Seoul. RESULTS: Cigarette smoking had a significant inverse association with systolic and diastolic blood pressure. Adjusted for age, body mass index (BMI), and alcohol consumption, the odds ratio of hypercho-lesterolemia (> or = 240 mg/dl) was 1.30 (95% confidence interval (CI) 1.09-1.55), lower high density lipoprotein (HDL) cholesterol (< 40 mg/dl) was 1.29 (95% CI 1.08-1.54), higher low density lipoprotein (LDL) cholesterol (> or = 160 mg/dl) was 1.30 (95% CI 1.07-1.56), and hypertriglyceridemia (> or = 200 mg/dl) was 1.40 (95% CI 1.16-1.68) among men who smoked 21-30 cigarettes per day compared with nonsmokers. Adjusted for age. BMI, and cigarette smoking in men who consumed 90-179 and 180-269 g/week of alcohol compared with nondrinkers, the odds ratio of hypertension was 1.73 (95% CI 1.01-3.00) and 1.48 (95% CI 1.01-2.17), respectively. Alcohol consumption had a significant protective effect (adjusted odds ratio: 0.60-0.78) against lower HDL cholesterol in all categories > or = 90 g of alcohol per week compared with nondrinkers. The adjusted odds ratio of hypertriglyceridemia was 1.17 (95% CI 1.04-1.31), and glucose intolerance (fasting blood sugar (FBS) > or = 120 mg/dl) was 1.27 (95% CI 1.11-1.14) among those who consumed > or = 360 g/week of alcohol compared with nondrinkers. CONCLUSIONS: In this Korean population study, although alcohol consumption increased HDL cholesterol, which might have a protective effect on coronary heart disease, cigarette smoking was associated with decreased blood pressure, smoking was confirmed to have dyslipidemic effect such as increasing total cholesterol, LDL cholesterol, triglyceride and decreasing HDL cholesterol, and alcohol consumption was confirmed to be associated with hypertension, hypertriglyceridemia, and glucose intolerance as in Caucasian. Further prospective intervention studies are needed for evaluating cardiovascular effects after cessation of smoking and drinking.

Adult↗

Gastric cancer risk in relation to Helicobacter pylori infection and subtypes of intestinal metaplasia.

Helicobacter pylori (H. pylori) infection and intestinal metaplasia (IM) are each associated with an increased risk of gastric cancer (GC). To explore further the influences of H. pylori and IM on GC, H. pylori and subtypes of IM were evaluated in 135 sex and age-matched case and control pairs. Odds ratios (ORs) with 95% confidence intervals of developing GC were calculated for each risk factor using multiple logistic regression analysis. ORs for H. pylori infection and IM were 2.43 (1.29-4.65) and 4.59 (2.58-8.16), respectively, and those for different IM subtypes gave values of 0.82 (0.28-2.36) for type I, 2.03 (0.95-4.34) for type II and 39.75 (14.34-110.2) for type III. Stratification analysis by histological subtype and stage of GC showed a particularly high OR for IM in intestinal type (12.8, 4.73-34.83) and early GC (6.40, 2.25-18.18). Our data indicate that both H. pylori and IM are related to GC risk. Type III IM is a more specific marker of premalignancy, with relevance, in particular, to the early and intestinal type of GC.

Adult↗

Overexpression of p53 in different subtypes of intestinal metaplasia and gastric cancer.

p53 immunostaining was evaluated in cancerous epithelia and adjacent intestinal metaplasia of 135 gastric cancer specimens. The differential p53 overexpression in different subtypes of intestinal metaplasia and gastric cancer suggests that type III intestinal metaplasia is the commonest lesion in dysplasia-carcinoma transition, particularly in the intestinal type of gastric cancer.

Humans↗

Surgical results in patients with dual hepatitis B- and C-related hepatocellular carcinoma compared with hepatitis B- or C-related hepatocellular carcinoma.

BACKGROUND: The purpose of our study was to report on the surgical outcomes of patients with hepatocellular carcinoma (HCC) with dual hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and to assess the differences in the surgical results between those patients and the patients with hepatitis B- or hepatitis C-related HCC. METHODS: The operative outcomes of 13 patients with hepatitis B surface antigen (HBsAg)-positive and hepatitis C antibody (HCV Ab)-positive (the BC-HCC group) results, 57 patients with HBsAg-positive and HCV Ab-negative (the B-HCC group) results, and 34 patients with HBsAg-negative and HCV Ab-positive (the C-HCC group) results, who had undergone hepatic resection from 1991 to 1995, were compared. RESULTS: The operative mortality rate within 1 month after operation for patients with BC-HCC was 7.7%. No statistically significant difference was found compared with the patients with B-HCC and C-HCC (5.3% and 5.9%, respectively). The postoperative course of patients with BC-HCC was complicated by liver failure, postoperative ascites, and wound infection in one patient each. Also, no statistically significant difference was found among the groups (23.1%, 22.8%, and 20.5% for patients with BC-HCC, B-HCC, and C-HCC, respectively). The overall 1-, 3-, and 5-year survival rates of patients with BC-HCC in this series were 75%, 50%, and 40%, respectively. The postoperative recurrence rate was 66.7%. No statistically significant differences were found between the various groups of the virus-related HCC on the overall survival rate and disease-free survival rate. CONCLUSIONS: Hepatic resection for HCC in patients with dual HBV and HCV infections was associated with slightly higher operative morbidity and mortality rates, but there were no statistical differences compared with hepatitis B- or C-related HCC regarding the survival and recurrence rates.

Carcinoma, Hepatocellular↗

The meaning and use of the cumulative rate of potential life lost.

BACKGROUND: The 'years of potential life lost' (YPLL) is a public health measure in widespread use. However, the index does not apply to the comparisons between different populations or across different time periods. It also has the limit of being cross-sectional in nature, quantifying current burden but not future impact on society. METHODS: A new years-lost index is proposed-the 'cumulative rate of potential life lost' (CRPLL). It is a simple combination of the 'cumulative rate' (CR) and the YPLL. Vital statistics in Taiwan are used for demonstration and comparison of the new index with existing health-status measures. RESULTS: The CRPLL serves the purpose of between-group comparison. It can also be considered a projection of future impact, under the assumption that the age-specific mortality rates in the current year prevail. For a rare cause of death, it can be interpreted as the expected years (days) of potential life lost during a subject's lifetime. CONCLUSIONS: The CRPLL has several desirable properties, rendering it a promising alternative for quantifying health status.

Adolescent↗

A generalizability study of a new standardized rating form used to evaluate students' clinical clerkship performances.

PURPOSE: To investigate the measurement characteristics of standardized clinical evaluation forms (CEFs) used to assign grades for clerkship performance. METHOD: In 1996-97, the authors reviewed 5,168 CEFs completed for 175 students in eight clerkships. Limiting their analysis to the three clerkships that produced the most CEFs, the authors conducted a generalizability study to determine the five variance components for each clerkship. A decision study then calculated the generalizability coefficients and standard errors of measurement in each clerkship for varied numbers of raters and CEF items. RESULTS: The generalizability study found large variance components attributable to rater and rating context. The decision study found that, when three or more raters completed CEFs for a student, the generalizability coefficient and standard error of measurement reached levels acceptable for grading. Increasing the number of items on the CEF had no significant effect. CONCLUSION: The reliability of assigning students clerkship grades based on single CEFs is unacceptably low. However, CEFs can accurately measure students' clerkship performances if completed by three or more raters.

Clinical Clerkship↗