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Biomedical subjects

T K Lee

Publications and source records attributed to T K Lee.

At least 73 records · Page 4Linked to original sources
PubMed1998

Identification of glutathione as a driving force and leukotriene C4 as a substrate for oatp1, the hepatic sinusoidal organic solute transporter.

oatp1 is an hepatic sinusoidal organic anion transporter that mediates uptake of various structurally unrelated organic compounds from blood. The driving force for uptake on oatp1 has not been identified, although a role for bicarbonate has recently been proposed. The present study examined whether oatp1-mediated uptake is energized by efflux (countertransport) of intracellular reduced glutathione (GSH), and whether hydrophobic glutathione S-conjugates such as leukotriene C4 (LTC4) and S-dinitrophenyl glutathione (DNP-SG) form a novel class of substrates for oatp1. Xenopus laevis oocytes injected with the complementary RNA for oapt1 demonstrated higher uptake of 10 nM [3H]LTC4 and 50 microM [3H]DNP-SG, and higher efflux of [3H]GSH (2.5 mM endogenous intracellular GSH concentration). The oatp1-stimulated LTC4 and DNP-SG uptake was independent of the Na+ gradient, cis-inhibited by known substrates of this transport protein and by 1 mM GSH, and was saturable, with apparent Km values of 0.27 +/- 0.06 and 408 +/- 95 microM, respectively. Uptake of [3H]taurocholate, an endogenous substrate of oatp1, was competitively inhibited by DNP-SG. Of significance, oatp1-mediated taurocholate and LTC4 uptake was cis-inhibited and trans-stimulated by GSH, and [3H]GSH efflux was enhanced in the presence of extracellular taurocholate or sulfobromophthalein, indicating that GSH efflux down its large electrochemical gradient provides the driving force for uptake via oatp1. The stoichiometry of GSH/taurocholate exchange was 1:1. These findings identify a new class of substrates for oatp1 and provide evidence for GSH-dependent oatp1-mediated substrate transport.

Animals↗
PubMed1998

Subtypes and case-fatality rates of stroke: a hospital-based stroke registry in Taiwan (SCAN-IV).

Stroke data bank can afford important information regarding risk factors, pathogenesis, prognosis, etc. By means of hospital-based stroke registry, we investigated the risk factors and case-fatality rates in different types of stroke and transient ischemic attack (TIA) patients at the National Taiwan University Hospital in 1995. After excluding ineligible patients, 995 patients aged 1-98 years (575 men and 420 women) were recruited. Men predominated in all age groups for stroke and TIA in general except for cerebral hemorrhage (CH) in patients aged < 35 years and subarachnoid hemorrhage (SAH) in patients aged > or = 45 years. Of these, 676 (67.9%), 41 (4.1%), 228 (22.9%) and 50 (5%) patients were classified in the categories of cerebral infarction (CI), TIA, CH and SAH, respectively. The CI/CH ratio was 2.96. Hypertension remained one of the most important risk factors for CI, CH and TIA patients. Severe extracranial carotid artery stenosis (> or = 50%) was found in 12% of the CI patients and 27% of the TIA patients, but not found in the CH and SAH patients. Of these patients, the 30-day case-fatality rate was 10.9%, highest in SAH (30%), followed by CH (24.1%) and CI (5.6%). There were 41 in-hospital stroke patients who had significantly higher case-fatality rates than the other stroke patients (P<0.001 for all stroke, CI and CH patients by chi2 test). As compared to the previous stroke registries in Taiwan, there is a secular trend of increasing CI/CH ratios. These findings in Taiwan were compared with those in other populations, including other Asian, Caucasian and black populations. The CI/CH ratios in Asian populations, including Chinese, Japanese and Korean, were much lower than those in Caucasian and black populations. Dietary, environmental and genetic factors probably play important roles in these differences.

Adolescent↗
PubMed1998

Comparison of blood pressure measured by oscillometry from the supraorbital artery and invasively from the radial artery.

In previous studies, oscillometric blood pressure measured from the supraorbital artery has been shown to agree quite well with pressure measured from the brachial artery in normal subjects. In this study, surgical patients whose conditions warranted the use of invasive blood pressure monitoring during the surgery were chosen. We compared systolic and diastolic blood pressure measured oscillometrically from the supraorbital artery with intraarterial blood pressures, measured invasively from the radial artery. A pressure bladder was attached to the forehead of each patient. The bladder was connected to a forehead blood pressure monitor. A catheter was inserted in a radial artery, and connected to a pressure monitor. Forehead blood pressure was measured every 5 min. Radial arterial pressure was averaged over the same period during which the forehead measurement was made. Blood pressures measured with the two methods were compared. For the systolic pressure, the difference between the two methods was -9.9 +/- 17.9 mm Hg (mean +/- SD). For diastolic pressure, the difference was -8.0 +/- 10.9 mm Hg. There was a significant difference between the two methods in the patient population chosen in this study.

Adult↗
PubMed1998

A 10-year review of drug seizures in Singapore.

The trend of illicit drug seizures and analysis in Singapore over a 10-year period from 1986 to 1995 was examined and reviewed. The main drugs were heroin, opium, cannabis, and illicit tablets containing benzodiazepines and amphetamines. The emergence of amphetamines in early 1996 was a major departure from the traditional drug abuse pattern in Singapore. Changes in the legal definitions of opium and cannabis were also reviewed.

Cross-Sectional Studies↗
PubMed1997

Reference spirometric values in healthy Chinese neversmokers in two townships of Taiwan.

The present community-based study was performed to provide predictive equations and lower boundaries of normal values for forced expiratory volume in one second (FEVI), forced vital capacity (FVC), and their percent ratio (FEV1%) in non-smoking, healthy adult men and women residing in communities, using ATS-recommended techniques and equipment. Use was made of data collected cross-sectionally from Nov. 1990 to Dec. 1993 in an ongoing longitudinal study on evolution of cardiovascular disease risk factors in Chinese. The spirometric values in our population reached their peak at around age 20. After age 20, a downward age trend was observed for FVC, FEV1, and FEV1%. Linear and negative relations were found in adults for each of the three spirometric values with age. Linear and positive relations were found between height and FVC or FEV1, but not between height and FEV1%. The age trends of FVC and FEV1 in Chinese adults were similar to those in Caucasians. Mean FVC and FEV1 levels of Chinese in Taiwan were systematically lower than those of Caucasians for a given height and a given age. Age and height specific percentile values of FVC and FEV1 and the age-specific percentile value of FEV1% are provided for adult men and women in this community study.

Adult↗
PubMed1997

Effectiveness of low-dose ASA in prevention of secondary ischemic stroke, the ASA Study Group in Taiwan.

This randomized double-blind controlled study was carried out to investigate the effect of 100 mg acetylsalicylic acid (ASA) per day on the secondary prevention of ischemic stroke. Patients who suffered a first ischemic stroke from 13 participating hospitals were enrolled. They were independent or only partially dependent in activities of daily living and all had received brain CT for diagnosis. Eligible patients were randomly allocated to the 100 mg ASA or the nicametate citrate (a vasodilator) groups, and trial medications were started within three to six weeks after the onset of stroke. The primary end point was cerebral reinfarction, and intracranial hemorrhage was classified as an adverse event. Four hundred and sixty-six patients participated in this study; and 222 cases (136 males and 86 females) were allocated to the ASA group while 244 cases (150 males and 94 females) were assigned to the nicametate group. No significant difference in baseline characteristics between the two groups was observed. Cerebral reinfarction developed 6.3% (14/222) in the ASA group and 11.9% (29/244) in the nicametate group. According to the Cox's proportional hazards model, the estimated risk ratio (ASA group vs. nicametate group) was 0.538, with a 95% confidence interval of 0.284-1.019. The result was of borderline statistical significance. The risk for cerebral reinfarction was reduced by almost 50% among those who took 100 mg ASA versus those who took nicametate.

Aged↗
PubMed1997

Secretion of human furin into mouse milk.

We have previously described the expression of the human proprotein convertase furin or paired basic amino acid-cleaving enzyme, in mice transgenic for paired basic amino acid-cleaving enzyme and human Protein C (HPC). Here we show 100-fold or higher expression of furin in the mammary gland, compared with endogenous furin. Furin and recombinant HPC were detected in the same regions of the mammary gland and regulated similar to the endogenous whey acidic protein. In addition to the expected intracellular localization, furin was secreted into the milk as an 80-kDa form lacking the transmembrane and cytoplasmic domains. Furin present at levels of up to 40,000 units/ml milk cleaved the t-butoxycarbonyl-RVRR-AMC substrate with a Km of 32 microM, and processed the recombinant HPC precursor at the appropriate sites. Surprisingly, the expression of an active protease was not toxic to the mammary gland. This is a rare example of an animal model secreting active truncated forms of a processing endoprotease into a bodily fluid.

Animals↗
PubMed1997

Transgenic pigs produce functional human factor VIII in milk.

Deficiency or abnormality of coagulation factor VIII (FVIII) causes a bleeding disorder called hemophilia A. Treatment involves FVIII concentrates prepared from pooled human plasma or recombinant FVIII (rFVIII) prepared from mammalian cell culture. The cost of highly purified FVIII or rFVIII is a major factor in hemophilia therapy and restricts prophylaxis. We have sought to generate a new source of rFVIII by targeting expression of the human FVIII cDNA to the mammary gland of transgenic pigs using the regulatory sequences of the mouse whey acidic protein gene. The identity of processed heterodimeric rFVIII was confirmed using specific antibodies, by thrombin digestion and activity assays. The secretion of as much as 2.7 micrograms/ml of rFVIII in milk was over tenfold higher than in normal plasma. Up to 0.62 U/ml of rFVIII was detected in an assay in which rFVIII restored normal clotting activity to FVIII-deficient human plasma.

Animals↗
PubMed1997

Reliability of finger stick capillary blood for the lymphocyte micronucleus assay.

Compared with peripheral blood sampling, capillary blood collecting by finger stick is less traumatic and more convenient. To assess the sensitivity and reliability of capillary blood for the lymphocyte micronucleus (MN) assay, this study was performed in three sample groups, i.e. healthy donors (n = 3), cancer patients before treatment (n = 7), and cancer patients who were undergoing fractionated partial-body radiotherapy (n = 9). For each group, we measured three intra-individual variables, i.e. micronucleus (MN) frequency, binucleate (BN) index, and micronucleated BN index of lymphocytes obtained from capillary blood and the corresponding peripheral blood. Our results indicated that in all three sample groups, the differences in these variables between capillary blood and peripheral blood either before or after ex vivo 137Cs irradiation (2 Gy) were insignificant. Since capillary blood is more accessible than peripheral blood, we believe that it is a reliable source for the lymphocyte MN assay especially when venipuncture is not convenient.

Adult↗
PubMed1997

Subtypes of ischemic stroke. A hospital-based stroke registry in Taiwan (SCAN-IV).

BACKGROUND AND PURPOSE: To better understand the clinical pattern and further elucidate the risk factors and outcome in different subtypes of cerebral infarction (CI) of the Chinese in Taiwan, we analyzed the National Taiwan University Hospital Stroke Registry in 1995 and performed an ethnic comparison with similar data banks. METHODS: From the National Taiwan University Hospital Stroke Registry in 1995, 676 patients (383 men and 293 women; mean age, 64.9 years; SD, 13.8 years; range, 1 to 98 years) with CI were recruited for this analysis. CI was classified into five subtypes based on clinical manifestations, ultrasonographic studies, and neuroimaging findings: large-artery atherosclerosis, lacunae, cardioembolism, other less common determined causes, and undetermined cause. Vascular risk factors, extracranial carotid artery atherosclerosis, and 30-day case-fatality rates were investigated in each subtype of CI. RESULTS: Of all CI patients, 17%, 29%, 20%, 6%, and 29% were classified as large-artery atherosclerosis, lacunae, cardioembolism, other determined causes, and undetermined cause subtypes, respectively. The present results were compared with those from eight similar Western stroke registries. The relative incidence of lacunar CI in Chinese patients was more common, but large-artery atherosclerotic CI was less common than in whites. Hypertension was frequently seen in CI patients, especially in those with lacunae (85%) and large-artery atherosclerosis (69%). Patients with cardioembolism had a higher percentage of atrial fibrillation (69%), left ventricular hypertrophy, and ischemic heart disease than the other patients. Patients with large-artery atherosclerosis had more vascular risk factors, such as hypertension, diabetes mellitus, smoking, and carotid stenosis. Cardioembolic patients had higher case-fatality rates than other CI patients. Of the cardioembolic patients, 17.3% and 21.8% died within 30 days and during hospitalization, respectively. CONCLUSIONS: The proportion of CI subtypes varied in different stroke registries. This may be partly due to applied classification criteria and racial-ethnic differences. Awareness of the risk factors and outcome in each subtype of stroke may afford further insights into the surveillance and treatment of cerebrovascular disease.

Adolescent↗
PubMed1997

Stroke prevalence in Taiwan. Findings from the 1994 National Health Interview Survey.

BACKGROUND AND PURPOSE: Stroke has been the second leading cause of death for all ages in Taiwan since 1983. However, despite the severity of the threat, stroke prevalence in Taiwan has not yet been addressed in a nationwide survey. In this study, the stroke prevalence in Taiwan was investigated using data from the 1994 National Health Interview Survey. METHODS: This nationwide survey sought to obtain a nationally representative sample of households in Taiwan by using three-stage stratified random sampling with a probability proportional to size. In the first stage, 58 townships were selected, from the 359 townships in Taiwan, according to their administrative structure and level of socioeconomic development. In the second stage, 149 basic administrative regions (tsun or li) were selected from the selected 58 townships. Finally, 3814 households were selected from the 149 selected tsuns or lis. Field interviews were carried out between October 1994 and December 1994. Follow-up interviews with families of stroke patients were made 2 years later. RESULTS: Of the selected households 3119, or 81.8%, responded. A total of 11925 persons were interviewed, and 71 of them were stroke patients, with a crude point prevalence rate of 5.95 per 1000. The stroke prevalence increased steadily with age, from 0.51 per 1000 in persons aged 35 to 44 years to 113.6 per 1000 in persons aged 85 years or over. There was a weak association with higher stroke prevalence for persons living in eastern Taiwan or those of lower educational level. The overall male/female prevalence ratio was 1.17. The results of follow-up interviews showed a cumulative mortality rate of 25.4% within the 2-year period and an ischemic/hemorrhagic stroke ratio of 1.33 in 35 patients whose stroke type could be validated. CONCLUSIONS: Age was the most important factor correlating to stroke prevalence. On the basis of this result, planning policies and programs for stroke prevention in Taiwan should give a higher priority to (1) aggressive primary prevention for aged people who are apparently at higher risk of stroke and (2) early reduction of stroke risk factors in younger aged people whose immediate risk of stroke is lower but would increase significantly with age.

Adult↗
PubMed1997

Abnormal circadian blood pressure changes in patients with acute cerebrovascular disorders.

The central neural mechanisms of circadian rhythm are well known in animal models but less so in humans. In this study we looked for correlations between abnormalities of circadian rhythm and the sites of stroke, with the aim of identifying the location regulating the circadian rhythm in humans. We investigated the circadian profiles of arterial pressure in 100 stroke patients by ambulatory blood pressure monitoring within 2 days after their first stroke. Patients also underwent brain computed tomography and measurements of plasma norepinephrine and adrenal hormones. A total of 52 patients (group A) had abnormal patterns of circadian blood pressure rhythm while 48 patients had normal patterns (group N). The risk of an abnormal 24-hour blood pressure pattern was strongly inversely correlated with the distance between the lesion and the hypothalamus. There was also a close positive correlation between the distance from the lesion to the hypothalamus and the circadian indices of arterial blood pressure (systolic and diastolic pressure) in both groups. Abnormal circadian changes in adrenal hormones were found in 30 of 52 patients in group A, and in nine of 48 patients in group N. Apparently, the circadian rhythm of blood pressure is modulated mainly by direct neural effects and partly by the hormonal effects of the hypothalamus and its associated neural pathways. Individualized antihypertensive treatment and additional monitoring for possible cardiac events should be performed for those at a high risk of autonomic dysfunction.

Acute Disease↗
PubMed1996

Activation of recombinant human protein C.

We have produced recombinant human Protein C (rHPC) in the milk of transgenic swine. After purification, we have analyzed the interaction of teh zymogen with Protac, thrombin/thrombomodulin and thrombin alone. The amidolytic and anticoagulant activities of rAPC after Protac activation were approximately 80% those of its human plasma counterpart. Upon the excision of the activation peptide by thrombin/thrombomodulin complex, both the natural and recombinant activation products had similar enzymatic and biological activities. This observation can be attributed to the difference in the mechanism of action between the two activators and structural differences between HPC and rHPC.

Animals↗
PubMed1996

Microchip implants on the anterior sacral roots in patients with spinal trauma: does it improve bowel function?

PURPOSE: This study evaluated the effect of anterior sacral roots stimulator implants on bowel function of patients with spinal cord trauma. METHOD: Eight patients with spinal cord injury and constipation had anterior sacral roots stimulator implants inserted for concomitant bladder dysfunction. Questionnaires on bowel function and anorectal manometry tests were given before and after insertion of the implants. RESULTS: Six patients achieved improvement in bowel function. Four of these patients could defecate spontaneously following stimulation. Two patients had no improvement in bowel function. Anorectal manometry studies showed a negative rectoanal pressure difference at the time of stimulation. All patients were unable to defecate during stimulation. Positive rectoanal pressure difference was recorded in the six patients who had improved bowel function. This may be attributable to the slower relaxation of the smooth rectal muscle compared with the easily fatigable striated external anal sphincter. CONCLUSION: Anterior sacral roots stimulator implants can improve bowel function in patients with spinal cord trauma.

Adult↗
PubMed1996

Supraorbital artery as an alternative site for oscillometric blood pressure measurement.

OBJECTIVE: Noninvasive blood pressure measured from the superficial temporal artery has been shown to correlate well with pressure in the brachial artery. The supraorbital artery may be an even better site for monitoring blood pressure on the forehead because it originates from the internal carotid artery, and it is easier to locate anatomically. This study compares mean pressure measured oscillometrically over the supraorbital artery and at the upper arm. METHODS: Oscillometric signals from the supraorbital artery were recorded in 20 surgical patients under general anesthesia using a 2.5- x 1-cm bladder attached to the forehead with a self-adhesive pad. Blood pressure was measured simultaneously from the arm using a Dinamap 1846 blood pressure monitor, and the resulting data compared with the supraorbital artery measurements. RESULTS: The mean difference between 219 pairs of blood pressure measurements, from the forehead and the arm, was 3.8 mm Hg. The standard deviation of the differences was 7.4 mm Hg. The linear regression equation for the data was y = 0.98x + 3.25, with a standard error of estimate of 7.31 mm Hg. The correlation coefficient between the two measurements was 0.82. CONCLUSIONS: The results show that mean blood pressures measured oscillometrically from the supraorbital and brachial arteries agree and correlate well with each other. The supraorbital artery should be a good alternative site for blood pressure measurement.

Adult↗
PubMed1996

Silk road: opportunities for foreign-owned health care clinics in China.

Hospitals and other health care providers are being squeezed by declining reimbursement and capitated revenues. As this happens they are looking to expand into rapidly developing and newly industrialised countries. This article will focus on the People's Republic of China as a country with opportunities for developing private hospitals and health care facilities.

China↗
PubMed1996

In hypercholesterolemia, lower peripheral monocyte count is unique among the major predictors of atherosclerosis.

Many studies have shown that enhanced monocyte adherence is an important factor in the initiation of atherosclerosis. Because the relationships between circulating monocyte count and atherosclerosis or its major predictors have received little attention, we conducted this study with the aim of clarifying these relationships. The study included 409 men and women who underwent a carotid artery duplex study and white blood cell analysis (Sysmex Cell Counter) during a 2-day health check at our hospital in 1994. We found no correlation between preexisting carotid atherosclerosis and monocyte count. After adjustment for age and sex, hypercholesterolemia, among the major predictors of atherosclerosis, showed a unique correlation with both lower monocyte count and percentage (P < .001, P < .0001, respectively), whereas smoking was correlated with a higher monocyte count (P < .001). There was a slight but nonsignificant increase in monocyte count in hypertension, diabetes, and hypertriglyceridemia. Our results imply that: (1) hypercholesterolemia has a strong, peripheral monocyte-reducing effect, probably due to direct enhancement of monocyte adhesion to the endothelium, which subsequently initiates the atherosclerotic process, and (2) the mechanisms of other predictor(s)-induced atherosclerosis may be quite different from that of hypercholesterolemia. Another possible explanation for the inverse correlation between monocyte count and serum cholesterol level is that decreased monocyte levels might lead to hypercholesterolemia because of decreased uptake of cholesterol from the plasma by less monocyte-derived macrophages. The reasons why preexisting carotid atherosclerosis did not correlate with monocyte count are also discussed.

Arteriosclerosis↗