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Biomedical subjects

H J Oh

Publications and source records attributed to H J Oh.

At least 19 recordsLinked to original sources

Birth of viable female dogs produced by somatic cell nuclear transfer.

Since the only viable cloned offspring born in dogs was a male, the purpose of the present study was to produce female puppies by somatic cell nuclear transfer (SCNT). Adult ear fibroblasts from a 2-month-old female Afghan hound were isolated and used as donor cells. In vivo-matured canine oocytes surgically collected (approximately 72h after ovulation) from the oviducts of 23 donors were used for SCNT. After removal of the cumulus cells, oocytes were enucleated, microinjected, fused with a donor cell, and activated. A total of 167 reconstructed SCNT embryos were surgically transferred (Day 0) into the oviducts of 12 recipient bitches (average 13.9 embryos/recipient, range 6-22) with spontaneous, synchronous estrous cycles. Three pregnancies were detected by ultrasonography on Day 23, maintained to term, and three healthy female puppies (520, 460, and 520g), were delivered by Caesarean section on Day 60. These puppies were phenotypically and genotypically identical to the cell donor. In conclusion, we have provided the first demonstration that female dogs can be produced by nuclear transfer of ear fibroblasts into enucleated canine oocytes.

Animals↗

Associations of serum minerals with body mass index in adult women.

OBJECTIVE: This cross-sectional study evaluated the association between serum minerals and body mass index in adult women. METHODS: One hundred and eighteen adult women were recruited by written advertisement from outpatient clinics or a health promotion center at a university hospital. Serum calcium, magnesium, copper and zinc were measured by an automatic analytical instrument and body mass index was calculated from height and weight. RESULTS: Serum magnesium was inversely associated with body mass index (beta=-0.283, P=0.001) whereas serum copper had a positive association with body mass index (beta=0.197, P=0.025) after adjusting for age, physical activity, energy intake, dietary fat, alcohol consumption, supplements and menopause status. No associations were found with serum calcium and zinc. CONCLUSION: Serum magnesium and copper may be involved in the regulation of body size in adult women.

Adult↗

The prevalence and risk factors associated with isolated untreated systolic hypertension in Korea: the Korean National Health and Nutrition Survey 2001.

Although isolated systolic hypertension (ISH) increases the risk of coronary heart disease and stroke, more than any other hypertension subtype, the prevalence and risk factors associated with ISH in the Korean population are not known. The 2001 Korean National Health and Nutrition Survey was a cross-sectional and nationally representative survey conducted in 2001. The prevalence of ISH by age and body mass index (BMI) was examined in 6601 Korean adults over 20 years of age. After adjusting for age, 4.32+/-0.32% of Korean adults had ISH, 5.28+/-0.37% had isolated diastolic hypertension and 5.82+/-0.36% had systolic/diastolic hypertension. The overall prevalence of ISH was found to increase directly with advancing age and increasing BMI. Although the ISH was found to be more common in men overall (4.81+/-0.50% in men, 4.12+/-0.37% in women), it was more common in women over 70 years of age. Independent variables associated with risk for ISH included advanced age, BMI, triglyceride (TG) levels, monthly income and alcohol intake. However, gender, fasting blood glucose, total cholesterol and high-density lipoprotein cholesterol levels, residential area, education level and smoking were found not to be significantly associated with ISH risk. The findings of the present study demonstrate that the prevalence of untreated ISH in Korea was lower than in Western countries. Age, BMI, TG levels, monthly income and alcohol intake were associated with ISH.

Adult↗

An easily integrative and efficient micromixer and its application to the spectroscopic detection of glucose-catalyst reactions.

The focus of this paper is on the fabrication of a PDMS-based passive efficient micromixer to be easily integrated into the other on-chip microfluidic system. The mixing is achieved by "strong stretching and folding," which employs a three-dimensional microchannel structure. By the simultaneously vertical and transversal dispersion of fluids, strong advection is developed. Owing to this powerful mixing performance (more than 70% of the mixing is accomplished within 2.3 mm over a wide range of Reynold number (Re)), the smaller integrative mixer can be realized. The feasibility and the potential usefulness of an integrative micromixer were evaluated by incorporating two mixers into the microchannel for the spectroscopic detection of a glucose-catalyst reaction. The results demonstrate a promising performance for diverse applications in the assay or synthesis of biological or chemical materials.

Biosensing Techniques↗

Catalyzed ozonation process with GAC and metal doped-GAC for removing organic pollutants.

The purpose of this study was to investigate the catalytic role of granular activated carbon (GAC), and metal (Mn or Fe) doped-GAC, on the transformation of ozone into more reactive secondary radicals, such as hydroxyl radicals (*OH), for the treatment of wastewater. The GAC doped with Mn showed the highest catalytic performance in terms of ozone decomposition into OH radicals. Likewise, activated carbon alone accelerated the ozone decomposition, resulting in the formation of *OH radicals. In the presence of promoters, the ozone depletion rate was enhanced further by the Mn-GAC catalyst system, even under aqueous acidic pH conditions.

Carbon↗

Azepanone-based inhibitors of human and rat cathepsin K.

The synthesis, in vitro activities, and pharmacokinetics of a series of azepanone-based inhibitors of the cysteine protease cathepsin K (EC 3.4.22.38) are described. These compounds show improved configurational stability of the C-4 diastereomeric center relative to the previously published five- and six-membered ring ketone-based inhibitor series. Studies in this series have led to the identification of 20, a potent, selective inhibitor of human cathepsin K (K(i) = 0.16 nM) as well as 24, a potent inhibitor of both human (K(i) = 0.0048 nM) and rat (K(i,app) = 4.8 nM) cathepsin K. Small-molecule X-ray crystallographic analysis of 20 established the C-4 S stereochemistry as being critical for potent inhibition and that unbound 20 adopted the expected equatorial conformation for the C-4 substituent. Molecular modeling studies predicted the higher energy axial orientation at C-4 of 20 when bound within the active site of cathepsin K, a feature subsequently confirmed by X-ray crystallography. Pharmacokinetic studies in the rat show 20 to be 42% orally bioavailable. Comparison of the transport of the cyclic and acyclic analogues through CaCo-2 cells suggests that oral bioavailability of the acyclic derivatives is limited by a P-glycoprotein-mediated efflux mechanism. It is concluded that the introduction of a conformational constraint has served the dual purpose of increasing inhibitor potency by locking in a bioactive conformation as well as locking out available conformations which may serve as substrates for enzyme systems that limit oral bioavailability.

Administration, Oral↗

Potent and selective cathepsin L inhibitors do not inhibit human osteoclast resorption in vitro.

Cathepsins K and L are related cysteine proteases that have been proposed to play important roles in osteoclast-mediated bone resorption. To further examine the putative role of cathepsin L in bone resorption, we have evaluated selective and potent inhibitors of human cathepsin L and cathepsin K in an in vitro assay of human osteoclastic resorption and an in situ assay of osteoclast cathepsin activity. The potent selective cathepsin L inhibitors (K(i) = 0.0099, 0.034, and 0.27 nm) were inactive in both the in situ cytochemical assay (IC(50) > 1 micrometer) and the osteoclast-mediated bone resorption assay (IC(50) > 300 nm). Conversely, the cathepsin K selective inhibitor was potently active in both the cytochemical (IC(50) = 63 nm) and resorption (IC(50) = 71 nm) assays. A recently reported dipeptide aldehyde with activity against cathepsins L (K(i) = 0.052 nm) and K (K(i) = 1.57 nm) was also active in both assays (IC(50) = 110 and 115 nm, respectively) These data confirm that cathepsin K and not cathepsin L is the major protease responsible for human osteoclastic bone resorption.

Bone Resorption↗

Effects of vehicles and enhancers on transdermal delivery of melatonin.

For a more effective transdermal delivery of melatonin (MT), the effects of vehicles and enhancers on its skin permeation and lag time were evaluated. Skin permeation study was conducted in Franz diffusion cells using excised hairless mouse skins. MT was analyzed by HPLC. As vehicles, ethanol (EtOH), polyethylene glycol 400 (PEG), or propylene glycol (PG) was used alone or mixed with a phosphate buffer. Binary vehicles (EtOH/buffer, PEG/buffer, PG/buffer) showed different effects on the skin permeation of MT and its lag time. Compared with the buffer alone, the PEG/buffer shortened the lag time of MT but reduced its skin permeation. EtOH/buffer significantly increased the flux of MT but prolonged the lag time with the content of EtOH. PG/buffer did not affect the lag time but slightly increased the skin permeation of MT at the higher content of PG (> or =80%). These results indicate that the composition of vehicles exerts significant influence but it per se might have limitation in modulating the transdermal delivery of MT. Next, one tested whether fatty acids could more effectively enhance the skin permeation of MT and shorten its lag time. Given the influence of vehicles on both permeation and lag time, PG was used as a vehicle for fatty acids. The permeation-enhancing effects of saturated fatty acids increased in the following order: C10>C12>C14>C16>C18. The saturated fatty acid, however, did not significantly shorten the lag time regardless of the carbon chain length. Meanwhile, similar to saturated lauric acid (C12), unsaturated oleic acid (C18) dramatically enhanced the skin permeability coefficient of MT more than 950-fold over the effect of PG alone. Moreover, oleic acid showed the shortest lag time (2.1 h). The results suggest that oleic acid in a suitable vehicle could more effectively enhance the skin permeation of MT and shorten its lag time than did the vehicles of various compositions.

Animals↗

Characterization of raw water for the ozone application measuring ozone consumption rate.

This study was conducted to illustrate an ideal method for characterizing natural waters for ozonation processes in drinking water treatment plants. A specific instrument designed with the flow injection analysis (FIA) technique enabled us to measure accurately the ozone decomposition rate, which was found to consist of two stages: the instantaneous ozone consumption stage and the slower ozone decay stage. The ozone consumption rate was measured at the initial and secondary stages by determining certain parameters called the instantaneous ozone demand (ID) and the pseudo first-order decay rate constant (k(c)). Using the OH*-probe, the yield of OH* per consumed ozone was also measured to determine its potential to produce OH* for the oxidation of micropollutants during the ozonation process. The ozone consumption of the ID values was significant in most natural waters, and substantial amounts of OH* were found to generate during the instantaneous ozone consumption stage. This study also investigated the effects of particulates, ozone doses, and sequential ozone injection on ozone decomposition kinetics and OH* formation yield.

Algorithms↗

Metabolic characteristics and prevalence of osteoporosis among women in Tae-An area.

Understanding the metabolic changes in women is one of the important ways to prevent and treat osteoporosis. To reveal the metabolic characteristics of 289 healthy women aged between 35-65 yr in Tae-An, Korea we evaluated the association between bone mass assessed by broadband ultrasound attenuation (BUA) using quantitative ultrasound 2 (QUS2) and various parameters such as age, body mass index, serum levels of alkaline phosphatase, calcium, phosphorus, parathyroid hormone, 25(OH)D, and urinary ratios of calcium/creatinine and deoxypyridinoline (Dpyd)/creatinine. Among the subjects, 3.0% were osteoporotic, and 40.9% were osteopenic. When the subjects were classified according to their years since menopause (YSM) and age, the prevalence of osteoporosis increased along with an increase of YSM and age. Bone turnover markers such as serum alkaline phosphatase and fasting urinary Dpyd/creatinine were significantly higher in the group with low bone mass than in the normal group. In summary, this study shows, by use of biochemical markers of bone turnover and QUS2, the prevalence of osteoporosis in women aged between 35-65 in Tae-An was 3.0% and the risk of low bone mass increased with the bone turnover markers.

Adult↗

Characterization of native interaction of hsp110 with hsp25 and hsc70.

The 110 kDa heat shock protein (HSP) (hsp110) has been shown to be a diverged subgroup of the hsp70 family and is one of the major HSPs in mammalian cells [1,2]. In examining the native interactions of hsp110, we observed that it is found to reside in a large molecular complex. Immunoblot analysis and co-immunoprecipitation studies identified two other HSPs as components of this complex, hsc70 and hsp25. When examined in vitro, purified hsp25, hsp70 and hsp110 were observed to spontaneously form a large complex and to directly interact with one another. When luciferase was added to this in vitro system, it was observed to migrate into this chaperone complex following heat shock. Examination of two deletion mutants of hsp110 demonstrated that its peptide-binding domain is required for interaction with hsp25, but not with hsc70. The potential function of the hsp110-hsc70-hsp25 complex is discussed.

Animals↗

Mammalian Hsp70 and Hsp110 proteins bind to RNA motifs involved in mRNA stability.

In this study, in vitro RNA binding by members of the mammalian 70-kDa heat shock protein (Hsp) family was examined. We show that Hsp/Hsc70 and Hsp110 proteins preferentially bound AU-rich RNA in vitro. Inhibition of RNA binding by ATP suggested the involvement of the N-terminal ATP-binding domain. By using deletion mutants of Hsp110 protein, a diverged Hsp70 family member, RNA binding was localized to the N-terminal ATP-binding domain of the molecule. The C-terminal peptide-binding domain did not bind RNA, but its engagement by a peptide substrate abrogated RNA binding by the N terminus of the protein. Interestingly, removal of the C-terminal alpha-helical structure or the alpha-loop domain unique to Hsp110 immediately downstream of the peptide-binding domain, but not both, resulted in considerably increased RNA binding as compared with the wild type protein. Finally, a 70-kDa activity was immunoprecipitated from RNA-protein complexes formed in vitro between cytoplasmic proteins of human lymphocytes and AU-rich RNA. These findings support the idea that certain heat shock proteins may act as RNA-binding entities in vivo to guide the appropriate folding of RNA substrates for subsequent regulatory processes such as mRNA degradation and/or translation.

3' Untranslated Regions↗

The chaperoning activity of hsp110. Identification of functional domains by use of targeted deletions.

hsp110 is one of major heat shock proteins of eukaryotic cells and is a diverged relative of the hsp70 family. It has been previously shown that hsp110 maintains heat-denatured luciferase in a soluble, folding competent state and also confers cellular heat resistance in vivo. In the present study the functional domains of hsp110 that are responsible for its chaperoning activity are identified by targeted deletion mutagenesis using the DnaK structure as the model. The chaperoning activity of mutants is assessed based on their ability to solubilize heat-denatured luciferase as well as to refold luciferase in the presence of rabbit reticulocyte lysate. It is shown that these functions require only an internal region of hsp110 that includes the predicted peptide binding domain and two immediately adjacent C-terminal domains. It is also shown that although hsp110 binds ATP, binding can be blocked by its C-terminal region.

Adenosine Triphosphate↗

Potent dipeptidylketone inhibitors of the cysteine protease cathepsin K.

Cathepsin K (EC 3.4.22.38) is a cysteine protease of the papain superfamily which is selectively expressed within the osteoclast. Several lines of evidence have pointed to the fact that this protease may play an important role in the degradation of the bone matrix. Potent and selective inhibitors of cathepsin K could be important therapeutic agents for the control of excessive bone resorption. Recently a series of peptide aldehydes have been shown to be potent inhibitors of cathepsin K. In an effort to design more selective and metabolically stable inhibitors of cathepsin K, a series of electronically attenuated alkoxymethylketones and thiomethylketones inhibitors have been synthesized. The X-ray co-crystal structure of one of these analogues in complex with cathepsin K shows the inhibitor binding in the primed side of the enzyme active site with a covalent interaction between the active site cysteine 25 and the carbonyl carbon of the inhibitor.

Cathepsin B↗

Use of papain as a model for the structure-based design of cathepsin K inhibitors: crystal structures of two papain-inhibitor complexes demonstrate binding to S'-subsites.

Papain has been used as a surrogate enzyme in a drug design effort to obtain potent and selective inhibitors of cathepsin K, a new member of the papain superfamily of cysteine proteases that is selectively and highly expressed in osteoclasts and is implicated in bone resorption. Here we report the crystal structures of two papain-inhibitor complexes and the rational design of novel cathepsin K inhibitors. Unlike previously known crystal structures of papain-inhibitor complexes, our papain structures show ligand binding extending deep within the S'-subsites. The two inhibitor complexes, carbobenzyloxyleucinyl-leucinyl-leucinal and carbobenzyloxy-L-leucinyl-L-leucinyl methoxymethyl ketone, were refined to 2.2- and 2.5-A resolution with R-factors of 0.190 and 0. 217, respectively. The S'-subsite interactions with the inhibitors are dominated by an aromatic-aromatic stacking and an oxygen-aromatic ring edge interaction. The knowledge of S'-subsite interactions led to a design strategy for an inhibitor spanning both subsites and yielded a novel, symmetric inhibitor selective for cathepsin K. Simultaneous exploitation of both S- and S'-sites provides a general strategy for the design of cysteine protease inhibitors having high specificity to their target enzymes.

Binding Sites↗

A causal model of voluntary turnover among nursing personnel in long-term psychiatric settings.

Causal modeling was used to explore the processes by which individual characteristics, job satisfaction, and intention to quit explain turnover among nursing personnel in 29 Department of Veterans Affairs (VA) long-term psychiatric settings. The sample consisted of 1,106 registered nurses (RNs), licensed practical nurses (LPNs), and nurses' aides. We conceptualized turnover as a multistage process linking social and experiential orientations, attitudes toward the job, the decision to quit, and the behavior of actually quitting. Intention to quit was the strongest direct predictor of turnover. Professional growth opportunities and workload were important indirect predictors of turnover. Dissatisfaction with work hazards and relationships with coworkers were both indirect and direct predictors of turnover. Attitudes towards the job varied by nursing group. LPNs and aides were less satisfied than RNs with autonomy and work hazards. RNs were more dissatisfied with workload. We conclude that strategies to promote retention need to address aspects of jobs tailored to specific nursing groups.

Adult↗