Biomedical subjects

C K Ho

Publications and source records attributed to C K Ho.

At least 37 records · Page 2Linked to original sources

PubMed2001

Importance of homodimerization for the in vivo function of yeast RNA triphosphatase.

Saccharomyces cerevisiae RNA triphosphatase Cet1 is an essential component of the yeast mRNA capping apparatus. The active site of Cet1 resides within a topologically closed hydrophilic beta-barrel (the triphosphate tunnel) that is supported by a globular hydrophobic core. The homodimeric quaternary structure of Cet1 is formed by a network of contacts between the partner protomers. By studying the effects of alanine-cluster mutations, we highlight the contributions of two separate facets of the crystallographic dimer interface to Cet1 function in vivo. One essential facet of the interface entails hydrophobic cross-dimer interactions of Cys(330) and Val(331) and a cross-dimer hydrogen bond of Asp(280) with the backbone amide of Gln(329). The second functionally relevant dimer interface involves hydrophobic side-chain interactions of Phe(272) and Leu(273). Ala-cluster mutations involving these residues elicited lethal or severe temperature-sensitive phenotypes that were suppressed completely by fusion of the mutated triphosphatases to the guanylyltransferase domain of mammalian capping enzyme. The recombinant D279A-D280A and F272A-L273A proteins retained phosphohydrolase activity but sedimented as monomers. These results indicate that a disruption of the dimer interface is uniquely deleterious when the yeast RNA triphosphatase must function in concert with the endogenous yeast guanylyltransferase. We also identify key residue pairs in the hydrophobic core of the Cet1 protomer that support the active site tunnel and stabilize the triphosphatase in vivo.

Acid Anhydride Hydrolases↗

PubMed2001

HIV-1 Tat protein interacts with mammalian capping enzyme and stimulates capping of TAR RNA.

HIV gene expression is subject to a transcriptional checkpoint, whereby negative transcription elongation factors induce an elongation block that is overcome by HIV Tat protein in conjunction with P-TEFb. P-TEFb is a cyclin-dependent kinase that catalyzes Tat-dependent phosphorylation of Ser-5 of the Pol II C-terminal domain (CTD). Ser-5 phosphorylation confers on the CTD the ability to recruit the mammalian mRNA capping enzyme (Mce1) and stimulate its guanylyltransferase activity. Here we show that Tat spearheads a second and novel pathway of capping enzyme recruitment and activation via a direct physical interaction between the C-terminal domain of Tat and Mce1. Tat stimulates the guanylyltransferase and triphosphatase activities of Mce1 and thereby enhances the otherwise low efficiency of cap formation on a TAR stem-loop RNA. Our findings suggest that multiple mechanisms exist for coupling transcription elongation and mRNA processing.

Animals↗

PubMed2001

A pilot evaluation of tibia lead concentrations in Taiwan.

BACKGROUND: The aims of this study were to examine some of the factors that influence tibia lead concentrations, tibia lead x-ray fluorescence measurement uncertainty and blood lead concentrations, and to compare tibia lead concentrations in Taiwanese lead workers to those observed in lead workers from other countries. METHODS: A pilot evaluation of 43 adult lead workers who underwent measurements of tibia lead and blood lead concentrations. RESULTS: Mean and maximum tibia lead concentrations were 54 microg of Pb per g of bone mineral(microg/g) and 193 microg/g, respectively. Mean and maximum blood lead concentrations were 44 microg/dl and 92 microg/dl, respectively. CONCLUSION: Past occupational control of lead exposure in Taiwan, ROC, did not prevent these workers from accumulating tibia lead concentrations greater than those in similar workers elsewhere in the world.

Adolescent↗

PubMed2001

Transforming growth factor beta may act as an autocrine-survival-promoting factor for transformed trophoblasts.

Using five trophoblast cell lines of different differentiation status, we have shown that trophoblasts could constitutively release the transforming growth factor beta-1 (TGFbeta1), but not TGFbeta2. Treatment of the human tumorigenic, TL, and BeWo cells with a differentiating agent and a potent protein kinase C activator--the tumor-promoting agent--or the JEG-3 cells with cholera toxin--a potent cyclic adenosine 3':5'monophosphate (cAMP) inducer--or its analogue 8-bromo-cAMP, potentiates TGFbeta production, but the two signaling pathways appear to be mutually exclusive. Surprisingly, the JAR tell line failed to respond to either type of TGFbeta activator. Based on reverse transcriptase (RT)-polymerase chain reaction (PCR), it was found that only the JAR cell line expressed messenger ribonucleic acid for decorin, a natural inhibitor of TGFbeta, and none of the cell lines had detectable protein expression as determined by immunocytochemical studies. The tell number in cultures with decorin was invariably lesser than in those without decorin under serum-free conditions for all the cell lines tested. These results suggest that TGFbeta may act as an autocrine-survival factor for transformed trophoblasts by allowing the cells to survive longer under a microenvironment which is not favorable for growth. Lastly, our results indicate that decorin, acting in a paracrine manner, may also play an important negative regulatory role in the development of transformed trophoblasts by sequestering TGFbeta, thereby preventing its action.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2001

Environmental and occupational skin diseases in Taiwan.

This presentation focuses on the four most important skin diseases in Taiwan thought to be of environmental and/or occupational origin. The majority of work-related dermatoses are contact dermatitis patients. Among occupational contact dermatitis patients, 58.5% involved irritant and 41.5%, allergic dermatitis. Electronics, hairdressing, medical practice, and construction were the most important occupations causing contact dermatitis. An endemic occurrence of chronic arsenism causing hyperpigmentation, keratosis, and cancer has been reported in Taiwan. Arsenical skin cancers present as multiple lesions at different disease stages. The skin cancers are usually found in non-sun-exposed areas. UVB exerts an inhibitory effect on the proliferation of arsenical cancers; this may explain its non-sun-exposed nature. An outbreak of premalignant and malignant skin lesions was reported among paraquat manufacturers in 1985. The skin lesions were mainly distributed over the sun-exposed areas. Photodamage and photocarcinogenesis revealed a strong association with exposure to bipyridines among paraquat manufacturers. In 1979, a mass poisoning occurred in Taiwan from cooking oil contaminated by polychlorinated biphenyls (PCBs). Over 60% of patients were in grades O-II by the Japanese classification. The blood PCB levels of the Taiwanese patients were found to be higher than those of the Yusho subjects.

Arsenic↗

PubMed2001

RNA triphosphatase component of the mRNA capping apparatus of Paramecium bursaria Chlorella virus 1.

Paramecium bursaria chlorella virus 1 (PBCV-1) elicits a lytic infection of its unicellular green alga host. The 330-kbp viral genome has been sequenced, yet little is known about how viral mRNAs are synthesized and processed. PBCV-1 encodes its own mRNA guanylyltransferase, which catalyzes the addition of GMP to the 5' diphosphate end of RNA to form a GpppN cap structure. Here we report that PBCV-1 encodes a separate RNA triphosphatase (RTP) that catalyzes the initial step in cap synthesis: hydrolysis of the gamma-phosphate of triphosphate-terminated RNA to generate an RNA diphosphate end. We exploit a yeast-based genetic system to show that Chlorella virus RTP can function as a cap-forming enzyme in vivo. The 193-amino-acid Chlorella virus RTP is the smallest member of a family of metal-dependent phosphohydrolases that includes the RNA triphosphatases of fungi and other large eukaryotic DNA viruses (poxviruses, African swine fever virus, and baculoviruses). Chlorella virus RTP is more similar in structure to the yeast RNA triphosphatases than to the enzymes of metazoan DNA viruses. Indeed, PBCV-1 is unique among DNA viruses in that the triphosphatase and guanylyltransferase steps of cap formation are catalyzed by separate viral enzymes instead of a single viral polypeptide with multiple catalytic domains.

Acid Anhydride Hydrolases↗

PubMed2001

The activity in ex vivo expansion of cord blood myeloid progenitor cells before and after cryopreservation.

A total of 50 human umbilical cord blood (UCB) samples were studied. The hematopoietic stem/progenitor (CD34+) populations were isolated from UCB mononuclear cells (MNC) by means of immunomagnetic separation. Double immunofluorescent staining of UCB CD34+ cells revealed that there was a high proportion (82.33 +/- 4.47%) of CD34+ cells co-expressing CD13, while the percentage of CD34+ CD33+ cells was much lower (22.17 +/- 3.35%). In contrast, for co-expressing lymphoid differentiation antigens, the proportion of CD34+CD38+ cells (38.34 +/- 6.09%) was relatively higher than that of CD34+CD10+ cells (11.52 +/- 1.24%) or CD34+CD2+ cells (9.84 +/- 2.30%). For stimulating the ex vivo expansion of UCB progenitor cells, no single hematopoietic growth factor (HGF) was efficacious when used alone, while combination of 4 HGFs, such as GM-CSF, G-CSF, IL-3, and SCF could induce a 55-fold increase in the myeloid progenitor cells, day-14 CFU-GM, in a short term of 7 days' liquid culture. Cryopreservation of UCB as MNC preparations at -196 degrees C could satisfactorily retain the number and activity of CD34+ cells. After thawing, a high recovery rate of about 80% CD34+ cells was obtained. When suspended in liquid cultures containing a combination of 4 HGFs, as shown above, the frozen cord blood progenitor cells could be well expanded, reaching a >50-fold increase in day-14 CFU-GM, which was very similar to that of the fresh UCB samples. In addition, a similar result was also seen in CFU-GEMM, indicating that after cryopreservation the recovered UCB progenitor cells retain an intact clonogeneic ability capable of efficiently responding to hematopoietic growth factors for ex vivo expansion.

ADP-ribosyl Cyclase↗

PubMed2001

Efficacy of zafirlukast in the treatment of patients with bronchial asthma.

Zafirlukast is a drug newly used for the treatment of asthma. In this study, we examined the efficacy of zafirlukast on asthmatic patients and compared this efficacy between patients in different age groups and with different severities of pulmonary function. Patients concurrently inhaled long-acting beta2-agonist, corticosteroid or taken an oral aminophylline regimen, were treated with 20 mg oral zafirlukast twice daily for 6 weeks. In total, 32 asthmatic patients were included in the study. The primary efficacy measures included morning and evening peak expiratory flows (PEFs); secondary efficacy measures were the scoring of asthma symptoms including sleeping, coughing, and wheezing scores. Pulmonary functions including forced expiratory flow in 1 sec (FEV1), forced vital capacity (FVC), and PEF rate (PEFR) were examined during each clinical visit. Results showed that oral zafirlukast administration resulted in improvements in morning and evening PEFs and asthma symptom scores with the following statistical p values: morning PEF (285.8 vs 308.4 L/min), p = 0.003; evening PEF (293.3 vs 312.1 L/min), p = 0.007; coughing score (1.03 vs 0.72), p = 0.011; and wheezing score (0.71 vs 0.51), p = 0.009. As to the pulmonary function during the clinical visit, only the improvement of PEFR reached a statistically significant level (74.3 vs 82, p = 0.017). We compared the efficacy between asthmatic patients of different ages and those with different severities of pulmonary function. In patients aged below 50 years, those with FEV1 above 80% of the predicted value and FVC above 85% of the predicted value were more responsive to zafirlukast. In conclusion, we demonstrate the efficacy of zafirlukast in asthma therapy particularly for those patients who are younger and have better pulmonary function. When asthmatic patients do not respond to inhaled corticosteroid, long-acting beta2-agonist, or oral aminophylline, zafirlukast may provide an adjunct effect for asthma therapy.

Administration, Oral↗

PubMed2001

Enhanced prostaglandin E2 secretion in sputum from asthmatic patients after zafirlukast therapy.

BACKGROUND AND PURPOSE: Leukotrienes are important inflammatory mediators of bronchial asthma that cause bronchoconstriction, mucous secretion, and increased vascular permeability. Current guidelines recommend anti-leukotriene agents as alternative treatments for asthma; however, data on their anti-inflammatory effect is lacking. METHODS: The purpose of this study was to determine the anti-inflammatory effect of zafirlukast, a leukotriene antagonist, in patients with bronchial asthma. A total of 30 adult patients with mild persistent asthma received 6 weeks of zafirlukast treatment. Peak expiratory flow rate (PEFR) was determined before and after therapy to assess clinical efficacy. Both serum and sputum samples were collected before and after therapy and concentrations of eosinophil cationic protein (ECP), prostaglandin E2 (PGE2), and leukotriene E4 (LTE4) were measured. RESULTS: A significant improvement in PEFR was found after zafirlukast therapy (p = 0.017). There was also a significant reduction in serum ECP concentration (13.6 +/- 2.4 micrograms/L vs 10.3 +/- 2.1 micrograms/L, p < 0.025) and a significant increase in sputum PGE2 concentration (112.7 +/- 14.0 pg/mL vs 176.8 +/- 32.1 pg/mL, p < 0.01). The percentage eosinophil count and the concentrations of ECP and LTE4 in the sputum were not significantly different after therapy. CONCLUSION: This study found a significant reduction in serum ECP and a significant increase in sputum PGE2 concentrations in asthmatic patients after zafirlukast treatment, both of which were significantly associated with improvement in PEFR. The modulation of PGE2 and ECP production might occur through the anti-inflammatory effect of zafirlukast.

Adult↗

PubMed2001

Two episodes of ethylene oxide poisoning--a case report.

Ethylene oxide is used as a sterilizer, a solvent, a plasticizer and in the manufacture of special solvents, antifreeze, polyester resins and non-ionic surfactants. Its toxicity is caused by an alkylating reaction with most organic substances in the body. Four workers, without any protection, managed the leakage of ethylene oxide from the collecting tank improperly on July 29, 2000. In the same factory, the overflow of ethylene oxide in process resulted in leakage of ethylene oxide again on Aug. 7, 2000. Two workers were poisoned despite wearing full-face respirators with ethylene oxide approved canisters. In these two events, the workers all smelled an ether-like odor. Six workers experienced nausea, vomiting, chest tightness, shortness of breath, dizziness, cough and ocular irritation. One worker had transient loss of consciousness. Oxygen therapy and supportive care were used. Patients were discharged in stable condition. The permissible exposure limit of ethylene oxide in air is 1 ppm as an eight hour TWA. Above 50 ppm, the odor threshold, a positive-pressure supplied air respirator is needed to protect the worker. Full-face respirators with ethylene oxide approved canisters could not protect our cases who smelled the odor and were exposed to an unknown concentration. It is important to wear positive-pressure self-contained breathing apparatuses equipped with full facepieces to clean up the contamination area and rescue the patients.

Adult↗

PubMed2001

Three-Dimensional Dynamic Subtraction Contrast Enhanced Magnetic Resonance Angiography of the peripheral arteries--an initial experience.

This is a prospective study with the objective of comparing Three Dimensional (3D) Dynamic Subtraction Contrast Enhanced Magnetic Resonance Angiography (3DDSCEMRA) with Conventional Catheter Arteriography (CCA) as the gold standard, in the diagnosis of peripheral occlusive disease. Three patients scheduled for CCA in this hospital in between September and October 2000 were included in this study. Patients underwent 3DDSCEMRA before proceeding to CCA on the same day. The 3DDSCEMRA reader was blinded to the CCA results. The results showed good correlation in iliofemoral segment and poor correlation in the infrapopliteal segment due to artifacts in 3DDSCEMRA images. 3DDSCEMRA is a new, non-invasive and promising technique in the diagnosis of peripheral occlusive disease.

Adult↗

PubMed2001

Traumatic transection of aorta.

A 16 year-old man presented with fracture of both his femurs after a road traffic accident. Chest radiograph revealed mediastinal widening. Subsequent CT scan and arch aortogram confirmed the findings of traumatic aortic arch transection at the isthmus. He underwent successful surgical repair. High index of suspicion and prompt actions are important in managing this potentially fatal but treatable condition.

Accidents, Traffic↗

PubMed2000

Sleep-related injury in the elderly--an epidemiological study in Hong Kong.

OBJECTIVES: Sleep-related injury is a serious but under-recognized condition. We examined the occurrence of sleep-related injuries and REM sleep behavior disorder (RSBD) in a community sample of elderly in Hong Kong. DESIGN: A representative sample of elderly aged 70 years or above were interviewed with a screening question on the presence of sleep-related injuries. Those who answered affirmatively as well as a subsample of negative responders were interviewed by clinicians. Patients with suspected sleep disorders underwent physical and psychiatric assessment as well as sleep studies. SETTING: NA. PATIENTS OR PARTICIPANTS: NA. INTERVENTIONS: NA. RESULTS: In total, 1034 elderly were surveyed and 0.8% reported history of sleep-related injury. Four subjects were confirmed to have RSBD, giving an estimated prevalence of RSBD of 0.38% (95% CI=0.01 to 0.76%). One subject had suspected RSBD but refused investigations while 1 had history suggestive of transient RSBD but could not be confirmed by the sleep studies. The course of RSBD in these subjects was that of a waxing and waning course instead of a progressive deterioration as described in previous literature. Two patients had been hospitalized for sleep-related injury before but their sleep disorder was not recognized. CONCLUSIONS: We found that sleep-related injury and RSBD were not rare in the elderly but were frequently under-recognized. Our study calls for greater attention to elderly who had sustained injury during sleep.

Aged↗

PubMed2000

Alterations in beta-adrenergic receptor density and adenylate cyclase activity in the rat brain treated chronically with lead.

Behavioral and memory impairment resulting from lead exposure is well known but the mechanism is not. We utilized the brain of lead exposed rats to investigate this problem. In an effort to elucidate the mechanism responsible for this alteration we examined blood and brain lead levels, brain beta-adrenoceptor density and cyclic AMP production in lead exposed rats. Wistar rats used in these trials were divided into six groups of ten animals each. Five groups were given drinking water containing 0.05, 0.1, 0.5, 1 and 2% lead acetate for a period of 60 days. One group (control group, 0% lead acetate) was given pure water. Application of a trend test indicated that both blood and brain lead levels increased significantly from group 0% to group 2% (group 0% <group 0.05% <group 0.1% <group 0. 5%<group 1%<group 2%), but that brain beta-adrenoceptor density and cyclic AMP levels stimulated by isoproterenol decreased (group 2%<group 1%<group 0.5%<group 0.1%<group 0.05%<group 0%). Kd did not vary among the six groups and this indicated that the affinity of the remaining beta-adrenoceptors for [125I]iodocyanopindolol was not changed. Linear regression analysis showed that beta-adrenoceptor density and stimulated cyclic AMP level in brain was found to be negatively correlated with brain lead level (P<0.001). The results show lead exposure that may be the result of an alteration of beta-adrenergic receptor and adenylate cyclase activity in brain.

Adenylyl Cyclases↗

PubMed2000

The change of beta-adrenergic system in lead-induced hypertension.

Lead exposure is considered to be a risk factor of cardiovascular disease. To investigate the relationship between lead and cardiovascular disease/hypertension in lead exposure, beta-adrenergic system is explored in this study. We address three topics in this study: (a) the relationship between beta-adrenergic receptor and lead level in heart, aorta, and kidney of lead-exposed rats; (b) the relationship between beta-adrenergic receptor in heart, aorta, kidney, and blood pressure in lead-exposed rats; and (c) the change of cyclic AMP level in heart, aorta, and kidney of rats with different lead levels. Wistar rats were chronically fed with 2, 1, 0. 5, 0.1, 0.05, and 0.01% lead acetate and water for 2 months. Plasma catecholamine level was measured by high-performance liquid chromatography. Radioligand binding assay was measured by a method that fulfilled strict criteria of beta-adrenoceptor using the ligand [(125)I]iodocyanopindolol. Cyclic AMP (cAMP) level was determined by radioimmunoassay. The levels of lead were determined by electrothermal atomic absorption spectrometry. The results showed that increased plasma norepinephrine level, decreased aorta beta-adrenergic receptor and cAMP, and increased kidney beta-adrenergic receptor and cAMP contributed to the elevation of blood pressure in lead-induced hypertension. The decrement of beta-adrenoceptor and cAMP in heart resulted in decreased contractility in heart.

Administration, Oral↗

PubMed2000

3-D reconstruction from tomographic data using 2-D active contours.

Reconstructing three-dimensional (3-D) shapes of structures like internal organs from tomographic data is an important problem in medical imaging. Various forms of the deformable surface model have been proposed to tackle it, but they are either computationally expensive or limited to tubular shapes. In this paper a 3-D reconstruction mechanism that requires only 2-D deformations is proposed. Advantages of the proposed model include that it is conformable to any 3-D shape, efficient, and highly parallelizable. Most importantly, it requires from the user an initial 2-D contour on only one of the tomograph slices to start with. Experimental results are shown to illustrate the performance of the model.

Computers↗

PubMed2000

A validity study of Ullanlinna Narcolepsy Scale in Hong Kong Chinese.

OBJECTIVE: To validate the Chinese version of Ullanlinna Narcolepsy Scale (CUNS). METHODS: A total of 234 subjects [163 male (69.7%) and 71 female (30.3%)] including 17 patients with narcolepsy, 21 normal controls and 196 patients with various sleep and psychiatric disorders were studied. The diagnoses of these patients were independently ascertained with sleep laboratory confirmation whenever indicated. All the subjects were interviewed through the telephone by a trained lay interviewer who was blind to the diagnosis. The questionnaire included demographic information, sleep habits and CUNS. RESULTS: Narcoleptic patients had a significantly higher CUNS score (18.6+/-4.7; 95% confidence interval (CI) 16.2-21.0) and differentiated well from all the other groups (F(6,227)=28.4, P<0.001). The CUNS has a satisfactory internal consistency with Cronbach's alpha of 0.75. The principal component analysis with varimax rotation revealed two factors, namely sleepiness and cataplexy factors, which accounted for 45.5% of the total variance. The best cut-off point for the CUNS scale was found to be at 13/14 with high specificity (93.5%), sensitivity (94.1%), negative predictive value (NPV, 99.5%) and modest positive predictive value (PPV, 53.3%). The AUC of receiver operating characteristic (ROC) analysis was 0.97 (95% CI 0.95-0.99). CONCLUSIONS: The CUNS was validated with satisfactory psychometric properties. The cross-cultural validation of UNS scale suggested that it could be used across the ethnic groups.

Adolescent↗

PubMed2000

Ouabain resistance of a human trophoblast cell line is not related to its reactivity to ouabain.

Ouabain is a specific inhibitor of sodium, potassium-dependent adenosine triphosphatase (Na,K-ATPase), a P-type ion-transporting ATPase which is essential for the maintenance of adequate concentrations of intracellular Na+ and K+ ions. The present study describes the establishment of a ouabain-resistant mutant, TLouaR, from a human trophoblast cell line TL. Morphologically TL and TLouaR are indistinguishable, but, TLouaR is about 1000 times more resistant to the cytotoxic effect of ouabain and > 2000 times to that of bufalin and yet ouabain can retard the growth of the TLouaR cells and in parallel reduce its cloning efficiency in a time- and dose-dependent manner. Furthermore, Na,K-ATPase activity from TLouaR cells is inhibitable by ouabain albeit with lower efficiency. [3H]ouabain binding studies reveal that TLouaR cells have less (P < 0.05) ouabain binding sites (1.7 +/- 0.15 x 10(4)/cell vs. 2.3 +/- 0.115 x 10(4)/cell in the control). However, affinities (dissociation constants Kd) to ouabain for TL and TLouaR cells are not significantly different. Lastly, Na,K-ATPase activity (1.375 +/- 0.25 micromole ATP/min mg protein) of TLouaR cells is significantly higher (P < 0.05) than that of the TL cells (0.895 +/- 0.12 micromole ATP/min x mg protein). These studies show that the interactions between ouabain and Na,K-ATPase can be mediated through different pathways resulting in diverse phenotypic characteristics. In addition, ouabain resistance does not necessarily reflect the lack of response to the digitalis drug. The exact mechanisms of ouabain resistance observed in the present study remain to be determined but the TLouaR cells may be the best tool to uncover the many functional characteristics of Na,K-ATPase.

Adenosine Triphosphatases↗