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Biomedical subjects

S J Lan

Publications and source records attributed to S J Lan.

At least 19 recordsLinked to original sources
PubMed2005

Amino acid concentrations in cerebrospinal fluid in children with acute lymphoblastic leukemia undergoing chemotherapy.

Cerebrospinal fluid (CSF) amino acid concentrations were measured in 45 children with acute lymphoblastic leukemia (ALL). Central nervous system (CNS) disease was absent in 34 and present in 11 (Groups L and M, respectively) at diagnosis. Thirty-two otherwise healthy children with febrile convulsions were studied for comparison. Results from this study show that glutamine levels at Day 0 were significantly higher in patients than in controls. Patients in Group M had elevated glutamine levels compared to Group L. In comparison, at Day 14, concentrations of glutamine and asparagine decreased, while glutamic acid amounts increased significantly in Group L. Glutamine levels fell at Day 42 in Group M, which may have resulted from more intensive treatment. From this study we hypothesise that higher baseline glutamine levels are indicative of a greater risk for CNS leukemia. Large-scale prospective trials are required to confirm increased baseline CSF glutamine levels in ALL patients, to identify glutamine as a marker for CNS disease and to clarify underlying mechanisms regulating glutamine in ALL.

Adolescent↗
PubMed2001

Arylcyclopropanecarboxyl guanidines as novel, potent, and selective inhibitors of the sodium hydrogen exchanger isoform-1.

A novel series of arylcyclopropanecarboxyl guanidines was synthesized and evaluated for activity against the sodium hydrogen exchanger isoform-1 (NHE-1). In biological assays conducted in an AP1 cell line expressing the human NHE-1 isoform, the starting cyclopropane 3a (IC(50) = 3.5 microM) shows inhibitory activity comparable to cariporide (IC(50) = 3.4 microM). Structure-activity relationships are used to optimize the affinity of various acyl guanidines for NHE-1 by screening the effect of substituents at both aryl and cyclopropyl rings. It is demonstrated that introduction of appropriate hydrophobic groups at the phenyl ring and a gem-dimethyl group at the cyclopropane ring enhances the NHE-1 inhibitory activity by up to 3 orders of magnitude (compound 7f, IC(50) = 0.003 microM). In addition, the gem-dimethyl series of analogues seem to display improved oral bioavailability and longer plasma half-life in rats. Furthermore, the lead benzodihydrofuranyl analogue 1 (BMS-284640) shows over 380-fold increased NHE-1 inhibitory activity as well as improved selectivity for NHE-1 over NHE-2 compared to cariporide.

Administration, Oral↗
PubMed2001

A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors.

A series of benzimidazole-based analogues of the potent MTP inhibitor BMS-201038 were discovered. Incorporation of an unsubstituted benzimidazole moiety in place of a piperidine group afforded potent inhibitors of MTP in vitro which were weakly active in vivo. Appropriate substitution on the benzimidazole ring, especially with small alkyl groups, led to dramatic increases in potency, both in a cellular assay of apoB secretion and especially in animal models of cholesterol lowering. The most potent in this series, 3g (BMS-212122), was significantly more potent than BMS-201038 in reducing plasma lipids (cholesterol, VLDL/LDL, TG) in both hamsters and cynomolgus monkeys.

Administration, Oral↗
PubMed1999

Tea consumption: fluid intake and bladder cancer risk in Southern Taiwan.

OBJECTIVES: To determine whether tea consumption and intake of other beverages increases bladder cancer risk. METHODS: A case-control study was conducted in Kaohsiung, Taiwan between August 1996 and June 1997. Index patients studied were consecutive patients with histologically confirmed, newly diagnosed bladder cancer in two major hospitals. For each patient, 4 controls were selected from patients with non-neoplastic and nonurologic diseases undergoing surgical operations in the same hospital and individually matched by sex, age, and date of admission. Using a structured questionnaire, a trained interviewer interviewed 40 patients and 160 controls. Conditional logistic regression analysis adjusting for ethnicity, family history, and smoking status and matching variables were used to estimate the odds ratio (OR) and 95% confidence interval (CI). RESULTS: Tea consumption overall was associated with increased bladder cancer risk (OR 3.29, 95% CI 1.34 to 8.05). Compared with non-tea drinkers, the odds ratios of bladder cancer for oolong tea drinkers was 3.00 (95% CI 1.20 to 7.47); for non-oolong tea drinkers (black and/or other green tea), it was 14.86 (95% CI 2.13 to 103.83). The risk was greater among those who began to drink tea before age 40 (OR 9.50, 95% CI 2.39 to 37.75) and those who had been drinking tea for more than 30 years (OR 17.75, 95% CI 3.00 to 105.17). Coffee, tap water, and alcohol consumption were associated with a slightly increased risk, and both soy juice and rice juice consumption were associated with reduced risk; none of these odds ratio estimates were statistically significant, however. CONCLUSIONS: Our results suggest that tea consumption is associated with an increased risk of bladder cancer.

Aged↗
PubMed1998

An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits.

Patients with abetalipoproteinemia, a disease caused by defects in the microsomal triglyceride transfer protein (MTP), do not produce apolipoprotein B-containing lipoproteins. It was hypothesized that small molecule inhibitors of MTP would prevent the assembly and secretion of these atherogenic lipoproteins. To test this hypothesis, two compounds identified in a high-throughput screen for MTP inhibitors were used to direct the synthesis of a highly potent MTP inhibitor. This molecule (compound 9) inhibited the production of lipoprotein particles in rodent models and normalized plasma lipoprotein levels in Watanabe-heritable hyperlipidemic (WHHL) rabbits, which are a model for human homozygous familial hypercholesterolemia. These results suggest that compound 9, or derivatives thereof, has potential applications for the therapeutic lowering of atherogenic lipoprotein levels in humans.

Alanine Transaminase↗
PubMed1998

Metabolism of alpha-phosphonosulfonate squalene synthase inhibitors. I. Disposition of a farnesylethyl alpha-phosphonosulfonate and ester prodrugs in rats.

The disposition of I [(E,E)-6,10,14-trimethyl-1-phosphono-5,9, 13-pentadecatriene-1-sulfonic acid] and its mono- (II), di- (III), and triester (IV) prodrugs in rats was studied with 14C-labeled compounds. After iv administration of I (15 micromol/kg), radioactivity in plasma was measurable up to 96 hr and averaged 0. 026 microg-eq/ml. I accounted for >50% of the radioactivity in plasma and had an apparent half-life of 4 hr. After oral administration of the same dose, the maximal plasma concentration of radioactivity averaged 0.108 microg-eq/ml at 6 hr. In 96 hr, 19 and 73% of the iv dose and 2 and 97% of the po dose was excreted in urine and feces, respectively. The absorption was 2.4%, based on the plasma data. In 12 hr after an iv dose of I to bile duct-cannulated rats, 41 and 14% of the dose was excreted in bile and urine, respectively. I accounted for 51% of the radioactivity in bile and a negligible amount in urine. At 12 hr after iv dosing, liver retained 31% of the dose. No accumulation of radioactivity in bone was observed. I (3%) and II (6%) were poorly absorbed. Enhanced absorption was observed for III (80%) and IV (45%). No I or metabolites of I were found in bile or urine of rats dosed with the prodrugs. The structures of two metabolites each for I, III, and IV were proposed. Together, they accounted for >80% of the radioactivity in urine and approximately 50% of the radioactivity in bile for each compound. Metabolism appeared to occur primarily at the farnesyl moiety, presumably by the same pathways as for farnesyl-1-pyrophosphate.

Animals↗
PubMed1997

Cancer mortality and residence near petrochemical industries in Taiwan.

An ecologic study design was used to investigate the relationship between cancer risks and residence in communities adjacent to petrochemical industrial counties (PICs). Directly age-adjusted mortality rates for cancer during 1982-1991 among 16 counties characterized by a heavy concentration of petrochemical industries were compared to rates among 16 matched counties with similar concentration of nonpetrochemical manufacturing industries, urbanization level, and demographic characteristics. An excess rate for liver cancer among males was found in the so-called PICs. The correlation could not be explained by confounding variables such as urbanization, socioeconomic class, or employment in nonpetrochemical industries. No other increased cancer risks were found to be associated with residence near petrochemical industries.

Age Factors↗
PubMed1997

Long-term vegetarian diet and bone mineral density in postmenopausal Taiwanese women.

This study examined bone density among postmenopausal Buddhist nuns and female religious followers of Buddhism in southern Taiwan and related the measurements to subjects characteristics including age, body mass, physical activity, nutrient intake, and vegetarian practice. A total of 258 postmenopausal Taiwanese vegetarian women participated in the study. Lumbar spine and femoral neck bone mineral density (BMD) were measured using dual-photon absorptimetry. BMD measurements were analyzed first as quantitative outcomes in multiple regression analyses and next as indicators of osteopenia status in logistic regression analyses. Among the independent variables examined, age inversely and body mass index positively correlated with both the spine and femoral neck BMD measurements. They were also significant predictors of the osteopenia status. Energy intake from protein was a significant correlate of lumbar spine BMD only. Other nutrients, including calcium and energy intake from nonprotein sources, did not correlate significantly with the two bone density parameters. Long-term practitioners of vegan vegetarian were found to be at a higher risk of exceeding lumbar spine fracture threshold (adjusted odds ratio = 2.48, 95% confidence interval = 1.03-5.96) and of being classified as having osteopenia of the femoral neck (3.94, 1.21-12.82). Identification of effective nutrition supplements may be necessary to improve BMD levels and to reduce the risk of osteoporosis among long-term female vegetarians.

Adult↗
PubMed1996

Effects of occupational dust exposure on the respiratory health of Portland cement workers.

The object of this study was to assess the relationship between occupational Portland cement dust exposure and respiratory health. Respiratory symptoms and ventilatory function were studied in a group of 591 male Portland cement workers employed in four cement plants. The prevalence of chronic respiratory symptoms was higher in exposed than in control workers. The exposed group had a significantly lower mean forced vital capacity (FVC), forced expiratory volume at 1 s (FEV1), and forced expiratory flows after exhalation of 50% and 75% of the vital capacity (FEF50, FEF75) than the control group. The data suggest that occupational exposure to Portland cement dust may lead to higher prevalence of chronic respiratory symptoms and the reduction of ventilatory capacity.

Adult↗
PubMed1996

Assessment of postpartum time-dependent disease risk in case-control studies: an application for examining age-specific effect estimates.

Among subjects who have experienced a biological event, such as menarche, menopause or a delivery, one cannot distinguish the effects of time since the event from age at the event due to the linear dependency among these time variables and age at study ('current age'). This is a well-known problem that also exists in the determination of the short- and long-term influence of childbirth on subsequent disease risk, since one must take into account in the analysis both current age and age at delivery. We describe an approach to assess in case-control studies the effect of a full-term pregnancy on time-dependent disease risk by including nulliparous women in the analysis and considering current age as a modifier of the effect of age at delivery. One then uses current age-specific odds ratio estimates that compare uniparous to nulliparous women to examine whether the relative rate of disease varies over time after a delivery. Analytic options include stratified analysis and modelling with interaction terms for unconditional or conditional logistic regression analysis. As an example, we have applied this analysis to a large case-control study that utilized record linkage between the Cancer Registry and the Fertility Registry of Sweden and that documented a transient increase in breast cancer risk after a childbirth, followed by a long-term reduction in this risk.

Adult↗
PubMed1996

A case-control study of oral cancer in Changhua County, Taiwan.

Forty oral cancer patients identified consecutively in Changhua Christian Hospital between 1990 and 1992 were compared with 160 population-based controls, matched for sex, age, area of residence, and educational background. Betel quid chewing was positively associated with the risk of oral cancer with adjusted odds ratio of 58.4 (95% CI: 7.6-447.6). The greater the number of years of chewing betel quid, the higher the risk of oral cancer; the adjusted odds rations were 12.9, 93.7 and 397.5 for < 21, 21-40, and > 40 years of betel chewing as compared with the non-users. The risk also increased with the quantity chewed per day; the odds ratios for those chewing < 10, 10-20 and > 20 quids/day were 26.4, 51.2 and 275.6, respectively. These odds ratio estimates were all statistically significantly different from the null value of unity.

Age Factors↗
PubMed1994

Dual effect of parity on breast cancer risk.

This study examined whether breast cancer risk increased for a short period after childbirth, but decreased after a longer period of time. Data from an international case-control study on breast cancer conducted in the 1960s were used to study the modifying effect of age at enrolment on the relationship between parity and breast cancer risk, comparing first uniparous with nulliparous women, and then biparous versus uniparous women. The statistical analysis was performed by modelling through multiple logistic regression, adjusting for study site, age at menarche, menopausal status and obesity index. Comparing uniparous with nulliparous women, an early age at birth seems to be protective for all periods after birth, whereas a late age at birth imparts a higher risk than nulliparity in the period immediately after birth, which declines with the passage of time. The modification effect by age was not apparent when biparous women with different age at second birth were compared with uniparous women. The results support the hypothesis that pregnancy oestrogens impart a transient increase of maternal breast cancer risk when the full-term pregnancy occurs late in a woman's life.

Adult↗
PubMed1993

Risk of extrahepatic bileduct cancer after cholecystectomy.

The aetiology of cancer of the extrahepatic bile duct is unknown. Gallstones have been proposed to be a risk factor on the basis of ecological and epidemiological evidence. As gallstones are formed in the gallbladder, the occurrence of extrahepatic bileduct cancer in patients after cholecystectomy is of interest. All patients (62,734) who had had a cholecystectomy during 1965-1983 within the Uppsala Health Care Region, Sweden, were followed up to the end of 1987. Excluding the first year of follow-up, 23 cancers of the extrahepatic bileduct occurred vs 26.3 expected for a standardised incidence ratio (SIR) of 0.88 (95% confidence interval [CI] 0.56-1.31). 10 years or more after operation there was a greater reduction of risk (SIR = 0.27; 95% CI 0.06-0.80). Similar patterns were observed for men and women, and among patients who had undergone cholecystectomy only compared with those who had had their common bileducts explored. To assess surveillance bias the incidence of primary liver cancer was also analysed: SIR = 1.15; 95% CI 0.91-1.44 overall, and 10 years or more after cholecystectomy SIR = 0.98; 95% CI 0.66-1.40. This study shows a reduced risk of extrahepatic bileduct cancer 10 or more years after cholecystectomy, indicating that gallstones may be a cause of this cancer.

Bias↗
PubMed1993

Breast-feeding and maternal smoking in the etiology of Crohn's disease and ulcerative colitis in childhood.

Medical records concerning pediatric or adolescent patients first diagnosed with Crohn's disease or ulcerative colitis in two New York hospitals during a 5-year period (1986 to 1990) were abstracted, and information concerning sex, age, race, birthplace, sibship size, birth order, maternal age at birth, month of birth, duration of breast-feeding, and maternal smoking was recorded. Medical records of patients presenting at the respective pediatric gastroenterology departments immediately before or after the patients with inflammatory bowel disease were seen were also abstracted in order to generate a control series. Data concerning 68 patients with Crohn's disease, 39 patients with ulcerative colitis, and 202 control patients were analyzed through multiple logistic regression. Breast-feeding was negatively associated with Crohn's disease (P approximately 0.04) and ulcerative colitis (P approximately 0.07), with relative risk point estimates around 0.5 and with evidence of duration-dependent trends in both instances. There was no evidence of association of either disease with maternal age at birth, birth order, maternal smoking, or season of birth.

Adolescent↗