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Biomedical subjects

S Park

Publications and source records attributed to S Park.

At least 37 records · Page 2Linked to original sources
PubMed2006

Suppressed expression of genes involved in transcription and translation in in vitro compared with in vivo cultured bovine embryos.

In vivo-derived bovine embryos are of higher quality than those derived in vitro. Many of the differences in quality can be related to culture environment-induced changes in mRNA abundance. The aim of this study was to identify a range of mRNA transcripts that are differentially expressed between bovine blastocysts derived from in vitro versus in vivo culture. Microarray (BOTL5) comparison between in vivo- and in vitro-cultured bovine blastocysts identified 384 genes and expressed sequence tags (ESTs) that were differentially expressed; 85% of these were down-regulated in in vitro cultured blastocysts, showing a much reduced overall level of mRNA expression in in vitro- compared with in vivo-cultured blastocysts. Relative expression of 16 out of 23 (70%) differentially expressed genes (according to P value) were verified in new pools of in vivo- and in vitro-cultured blastocysts, using quantitative real-time PCR. Most (10 out of 16) are involved in transcription and translation events, suggesting that the reason why in vitro-derived embryos are of inferior quality compared with in vivo-derived embryos is due to a deficiency of the machinery associated with transcription and translation.

Animals↗
PubMed2006

Differential responses of the growth hormone axis in two rat models of streptozotocin-induced insulinopenic diabetes.

The impact of streptozotocin (STZ)-induced, insulinopenic diabetes on the GH axis of rats and mice differs from study to study, where this variation may be related to the induction scheme, severity of the diabetes and/or the genetic background of the animal model used. In order to begin differentiate between these possibilities, we compared the effects of two different STZ induction schemes on the GH axis of male Sprague-Dawley rats: (1) a single high-dose injection of STZ (HI STZ, 80 mg/kg, i.p.), which results in rapid chemical destruction of the pancreatic beta-cells, and (2) multiple low-dose injections of STZ (LO STZ, 20 mg/kg for 5 consecutive days, i.p.), which results in a gradual, autoimmune destruction of beta-cells. STZ-treated animals were killed after 3 weeks of hyperglycemia (>400 mg/dl), and in both paradigms circulating insulin levels were reduced to <40% of vehicle-treated controls. HI STZ-treated rats lost weight, while body weights of LO STZ-treated animals gradually increased over time, similar to vehicle-treated controls. As previously reported, HI STZ resulted in a decrease in circulating GH and IGF-I levels which was associated with a rise in hypothalamic neuropeptide Y (NPY) mRNA (355% of vehicle-treated controls) and a fall in GH-releasing hormone (GHRH) mRNA (45% of vehicle-treated controls) levels. Changes in hypothalamic neuropeptide expression were reflected by an increase in immunoreactive NPY within the arcuate and paraventricular nuclei and a decrease in GHRH immunoreactivity in the arcuate nucleus, as assessed by immunohistochemistry. Consistent with the decline in circulating GH and hypothalamic GHRH, pituitary GH mRNA levels of HI STZ-treated rats were 58% of controls. However, pituitary receptor mRNA levels for GHRH and ghrelin increased and those for somatostatin (sst2, sst3 and sst5) decreased following HI STZ treatment. The impact of LO STZ treatment on the GH axis differed from that observed following HI STZ treatment, despite comparable changes in circulating glucose and insulin. Specifically, LO STZ treatment did suppress circulating IGF-I levels to the same extent as HI STZ treatment; however, the impact on hypothalamic NPY mRNA levels was less dramatic (158% of vehicle-treated controls) where NPY immunoreactivity was increased only within the paraventricular nucleus. Also, there were no changes in circulating GH, hypothalamic GHRH or pituitary receptor expression following LO STZ treatment, with the exception that pituitary sst3 mRNA levels were suppressed compared with vehicle-treated controls. Taken together these results clearly demonstrate that insulinopenia, hyperglycemia and reduced circulating IGF-I levels are not the primary mediators of hypothalamic and pituitary changes in the GH axis of rats following HI STZ treatment. Changes in the GH axis of HI STZ-treated rats were accompanied by weight loss, and these changes are strikingly similar to those observed in the fasted rat, which suggests that factors associated with the catabolic state are critical in modifying the GH axis following STZ-induced diabetes.

Animals↗
PubMed2005

Statics and dynamics of incommensurate spin order in a geometrically frustrated antiferromagnet CdCr2O4.

Using elastic and inelastic neutron scattering we show that a cubic spinel, CdCr2O4, undergoes an elongation along the c axis (c > a = b) at its spin-Peierls-like phase transition at T(N) = 7.8 K. The Néel phase (T < T(N)) has an incommensurate spin structure with a characteristic wave vector Q(M) = (0, delta,1) with delta approximately 0.09 and with spins lying on the ac plane. This is in stark contrast to another well-known Cr-based spinel, ZnCr2O4, that undergoes a c-axis contraction and a commensurate spin order. The magnetic excitation of the incommensurate Néel state has a weak anisotropy gap of 0.6 meV and it consists of at least three bands extending up to 5 meV.

Journal Article↗
PubMed2005

Socioaffective factors modulate working memory in schizophrenia patients.

Working memory deficit in schizophrenia is a core cognitive feature of the disorder and is reliably associated with abnormalities of the prefrontal circuitry. Working memory deficits are also associated with impaired social functioning and present a major obstacle toward successful rehabilitation in schizophrenia. Although the role of prefrontal cortex in working memory has been extensively investigated, the intricate relations among the prefrontal circuitry, working memory and social behaviors are not clearly understood. In this study, we manipulated social context and observed its effects on spatial working memory. In experiment 1, the effects of social and asocial reinforcements on spatial working memory were examined in schizophrenic patients and healthy controls. The results show that social but not asocial reinforcements facilitated spatial working memory in schizophrenic patients. In experiment 2, the effects of human voice reinforcements (with or without affect) on working memory was investigated. Voice reinforcements did not facilitate working memory relative to the no-reinforcement condition. There was no difference between high-affect vs flat-affect voice conditions. In experiment 3, the effects of direct and indirect social interactions on spatial working memory were studied. Direct but not indirect social interaction facilitated working memory in schizophrenic patients. These results suggest that social context might facilitate working memory in schizophrenic patients perhaps by activating frontal lobe systems. In addition, the possibility of improving cognitive functions such as working memory using seemingly non-cognitive methods might lead to potential remediation strategies.

Adult↗
PubMed2005

In vivo organ mass of Korean adults obtained from whole-body magnetic resonance data.

In vivo organ mass of the Korean adult, male and female were presented for the purpose of radiation protection. A total of 121 healthy volunteers (66 males and 55 females), whose body dimensions were close to that of average Korean adults, were recruited for this study. Whole-body magnetic resonance (MR) images were obtained, and contours of 15 organs (brain, eye, gall bladder, heart, kidney, liver, lung, pancreas, stomach, spleen, testes, thymus, thyroid, urinary bladder and uterus) and 9 bones (femur, tibia + fibula, humerus, radius + ulna, pelvis, cervical spine, thoracic and lumber spine, skull and clavicle) were segmented for organ volume rendering by anatomists using commercial software. Organ and bone masses were calculated by multiplying the Asian reference densities of the corresponding organs and bones by the measured volumes. The resulting organ and bone masses were compared with those of the International Commission of Radiological Protection (ICRP) and the Asian reference data. Significantly large standard deviation was shown in the moving organs of the respiratory and circulatory systems and in the alimentary and urogenital organs that are variable in volume in a single person. Gall bladder and pancreas showed unique Korean organ masses compared with those of ICRP and the Asian reference adults. Different from anatomical data based on autopsy, the in vivo volume and mass in this study can more exactly describe the organ volume of a living human subject for radiation protection. A larger sample size would be required for obtaining statistically more reliable results. It is also needed to establish the reference organ mass of younger age groups for which it is difficult to recruit volunteers and to immobilise the subjects for long-time MR scanning. At present, the data from this study will contribute to the establishment of a Korean reference database.

Adult↗
PubMed2005

[Whipple disease, initially diagnosed as sarcoidosis].

INTRODUCTION: Whipple disease is a multisystem infectious disease caused by Tropheryma whipplei. We report a case in which an initial diagnosis of sarcoidosis was changed to Whipple disease endocarditis. CASE: Based on clinical, radiographic, endoscopic and histologic findings, this 61-year-old man was diagnosed with sarcoidosis. Initial response to corticotherapy was good, but the patient required 35 mg of prednisone daily. The subsequent onset of clinical and laboratory signs of inflammation cast doubt on the diagnosis. After cardiac ultrasound revealed a mass 1 cm in diameter on the mitral valve, apparently vegetation, we diagnosed culture-negative infective endocarditis and ruled out most possible causes. PCR of a duodenal biopsy sample showed Tropheryma whipplei, thus confirming the diagnosis of Whipple disease, despite normal histological findings. After 3 weeks of intravenous gentamicin and amoxicillin treatment, oral cotrimoxazole was substituted. Follow-up transesophageal ultrasound showed no mitral vegetation. The patient, still under cotrimoxazole, has been off prednisone for 13 months and is completely asymptomatic. CONCLUSION: This case is an illustration of the difficulty in distinguishing Whipple disease from sarcoidosis in practice and of the importance of that distinction.

Anti-Bacterial Agents↗
PubMed2005

Feedback equilibrium control during human standing.

Equilibrium maintenance during standing in humans was investigated with a 3-joint (ankle, knee and hip) sagittal model of body movement. The experimental paradigm consisted of sudden perturbations of humans in quiet stance by backward displacements of the support platform. Data analysis was performed using eigenvectors of motion equation. The results supported three conclusions. First, independent feedback control of movements along eigenvectors (eigenmovements) can adequately describe human postural responses to stance perturbations. This conclusion is consistent with previous observations (Alexandrov et al., 2001b) that these same eigenmovements are also independently controlled in a feed-forward manner during voluntary upper-trunk bending. Second, independent feedback control of each eigenmovement is sufficient to provide its stability. Third, the feedback loop in each eigenmovement can be modeled as a linear visco-elastic spring with delay. Visco-elastic parameters and time-delay values result from the combined contribution of passive visco-elastic mechanisms and sensory systems of different modalities.

Adult↗
PubMed2005

Cell motility and local viscoelasticity of fibroblasts.

Viscoelastic changes of the lamellipodial actin cytoskeleton are a fundamental element of cell motility. Thus, the correlation between the local viscoelastic properties of the lamellipodium (including the transitional region to the cell body) and the speed of lamellipodial extension is studied for normal and malignantly transformed fibroblasts. Using our atomic force microscopy-based microrheology technique, we found different mechanical properties between the lamellipodia of malignantly transformed fibroblasts (H-ras transformed and SV-T2 fibroblasts) and normal fibroblasts (BALB 3T3 fibroblasts). The average elastic constants, K, in the leading edge of SV-T2 fibroblasts (0.48 +/- 0.51 kPa) and of H-ras transformed fibroblasts (0.42 +/- 0.35 kPa) are significantly lower than that of BALB 3T3 fibroblasts (1.01 +/- 0.40 kPa). The analysis of time-lapse phase contrast images shows that the decrease in the elastic constant, K, for malignantly transformed fibroblasts is correlated with the enhanced motility of the lamellipodium. The measured mean speeds are 6.1 +/- 4.5 microm/h for BALB 3T3 fibroblasts, 13.1 +/- 5.2 microm/h for SV-T2 fibroblasts, and 26.2 +/- 11.5 microm/h for H-ras fibroblasts. Furthermore, the elastic constant, K, increases toward the cell body in many instances which coincide with an increase in actin filament density toward the cell body. The correlation between the enhanced motility and the decrease in viscoelastic moduli supports the Elastic Brownian Ratchet model for driving lamellipodia extension.

Animals↗
PubMed2005

Depth profile of uncompensated spins in an exchange bias system.

We have used the unique spatial sensitivity of polarized neutron and soft x-ray beams in reflection geometry to measure the depth dependence of magnetization across the interface between a ferromagnet and an antiferromagnet. The net uncompensated magnetization near the interface responds to applied field, while uncompensated spins in the antiferromagnet bulk are pinned, thus providing a means to establish exchange bias.

Journal Article↗
PubMed2005

ECop (EGFR-coamplified and overexpressed protein), a novel protein, regulates NF-kappaB transcriptional activity and associated apoptotic response in an IkappaBalpha-dependent manner.

In the present study, we describe the function of a novel protein, ECop (EGFR-Coamplified and overexpressed protein), in the regulation of NF-kappaB activity. Ectopic expression of ECop increases NF-kappaB transcriptional activity by promoting nuclear translocation and DNA binding of NF-kappaB, and ECop-induced NF-kappaB activation confers cellular resistance to apoptotic challenge. In ECop knockdown cells, NF-kappaB transcriptional activity is suppressed due to delayed IkappaBalpha degradation, which results in a delayed nuclear translocation as well as decreased DNA binding of NF-kappaB. Suppression of NF-kappaB activation by ECop knockdown increases cellular susceptibility to apoptosis. These results suggest that ECop is a key regulator of NF-kappaB signaling, and that high-level, amplification-mediated ECop expression, such as that occurring in tumors with amplified EGFR, could contribute to resistance to apoptosis.

Apoptosis↗
PubMed2005

The significance and clinical factors associated with a subcentimeter resection of colorectal liver metastases.

BACKGROUND: Prognosis after resection of colorectal liver metastases is influenced by various factors. A positive margin of resection (MOR) has been shown to adversely influence prognosis. Although a 1-cm MOR has been accepted as adequate, the data to support this guideline are sparse. METHODS: Our hepatobiliary database was queried for patients who underwent liver resection for colorectal metastases between January 1992 and July 2003. All patients were divided into three groups: MOR <.5 cm (group A), .5 to 1 cm (group B), and >1 cm (group C). Operative reports from each hepatic resection were analyzed to determine local factors that may have contributed to a subcentimeter MOR. RESULTS: A total of 112 patients (67 men and 45 women) underwent liver resection for colorectal metastases with negative margins. Fifty-three patients were in group A, 26 patients were in group B, and 33 patients were in group C. Group C demonstrated decreased local recurrence (LR; P = .003), distant recurrence (DR; P = .008), and disease-free recurrence (P = .002). A significant difference in the overall time to LR (P = .003), time to DR (P = .003), and disease-free survival (P = .002) was also demonstrated. Factors associated with a subcentimeter MOR included nonanatomical resection (P = .043), proximity to a major vessel (P = .003), and central location (P = .002). CONCLUSIONS: A <1-cm resection for colorectal liver metastases is associated with increased LR and DR, as well as decreased disease-free survival. When a nonanatomical resection is performed, a MOR >1 cm should be attempted, because an adequate margin is often underestimated. Considerations should be made for extended resections when tumors are centrally located or near major vessels.

Aged↗
PubMed2005

Reproducibility of postexercise ambulatory blood pressure in Stage I hypertension.

The accuracy and reproducibility of ambulatory blood pressure monitoring used in intervention and treatment studies is essential to assure the desired health outcomes. The reproducibility of ambulatory variables in pharmacological studies has been reported, however, the reproducibility of ambulatory blood pressure variables associated with exercise has not been reported. Thus, the purpose of this study was to investigate the reproducibility of the postexercise ambulatory blood pressure in Stage I hypertensive adults. It was hypothesized that the reproducibility of the ambulatory blood pressure variables would not be different following two corresponding exercise and control treatments. A total of 18 Stage I hypertensive adults (142.1+/-3.15/91.6+/-1.80 mmHg) performed four randomized, 24 h AmBP monitoring sessions: two following a 50 min treadmill walk (50% VO(2) peak) and two on control days. Variables measured were: (1) average systolic and diastolic pressures for 24 h, daytime (06:00-22:00 h) and night time (22:00-06:00 h) and (2) systolic and diastolic load for the same time periods. Both a nonsignificant paired t-test and an excellent intraclass correlation were used to define reproducibility of the variables between the 1st and 2nd exercise trials and between the 1st and 2nd control trials. Reproducibility was found for all the control variables except for nighttime diastolic load. Reproducibility was found for all the systolic and diastolic exercise variables. Ambulatory blood pressure measurements, including average systolic and diastolic blood pressures and systolic and diastolic loads for 24 h, daytime and night time periods are reproducible following exercise.

Adult↗
PubMed2005

Time of day for exercise on blood pressure reduction in dipping and nondipping hypertension.

UNLABELLED: Time of day (TOD) for exercise may influence blood pressure (BP) reduction in hypertension because of the diurnal variation of BP and the duration of BP reduction following a single bout of exercise. The purpose of this study was to observe the effects of TOD for exercise on ambulatory blood pressure reduction in dipping (n=5) and nondipping (n=9) hypertension (<10% drop in nighttime BP (BP(night))). HYPOTHESES: (1) evening exercise (PM(ex)) would exhibit a greater BP(night) reduction in Non-Dippers than Dippers, (2) morning exercise (AM(ex)) would exhibit similar daytime BP (BP(day)) reduction in Dippers and Non-Dippers, (3) AM(ex) would exhibit greater 24 h BP (BP(24 h)) reduction than PM(ex) in Dippers, and (4) AM(ex) and PM(ex) would exhibit similar BP(24 h) reduction in Non-Dippers. BP responses to AM(ex) (0600-0800 h; 30 min at 50% VO(2peak)) and PM(ex) (1700-1900 h) were compared to each control day in a randomized design. Systolic (S) and diastolic (D) BP were averaged for BP(24 h), BP(day), and BP(night). A two-way ANOVA (dipping X time of exercise) using BP reduction with repeated measures were performed at P<0.05. FINDINGS: (1) Non-Dippers respond to exercise despite of TOD for exercise, (2) PM(ex) exhibited a greater SBP(night) reduction in Non-Dippers than Dippers, (3) AM(ex) exhibited similar SBP(day) reductions in Dippers and Non-Dippers, and (4) AM(ex) and PM(ex) exhibited similar SBP(24 h) reduction in Dippers and Non-Dippers. Dippers and Non-Dippers respond differently to TOD for exercise. The duration of the BP reduction persists up to 24 h after exercise.

Blood Pressure Monitoring, Ambulatory↗
PubMed2005

Characterization of Aspergillus fumigatus mutants with reduced susceptibility to caspofungin.

Caspofungin acetate (CAS) is a member of a new class of clinically-approved echinocandin drugs to treat invasive aspergillosis. CAS inhibits the activity of beta-1,3-D-glucan synthase (GS), thus damaging the fungal cell wall. Although no clinical resistance of Aspergillus to CAS has been reported as yet, the development of in vitro reduced susceptibility is presumed to be inevitable. By contrast, echinocandin resistance in laboratory strains of Candida albicans and Saccharomyces cerevisiae has been well documented. To study the potential for clinical resistance in Aspergillus, two classes of Aspergillus fumigatus mutant strains were isolated that exhibited reduced susceptibility to CAS. In the first class, a site-directed mutation within the target gene (AfFKS1, encoding the putative catalytic subunit of GS) was introduced and shown to confer low-level (16-fold) reduced susceptibility. A second class of spontaneous mutants were sensitive to low levels of drug but displayed nearly normal growth above 0.5 microg/ml, suggesting induction of an unknown resistance mechanism. At higher levels of drug (> or = 16 microg/ml), the mutants displayed partially restored sensitivity. Preliminary studies indicate that neither target site mutations, nor changes in target gene expression are present in these strains, as has been documented for several yeasts. Instead, preliminary results indicate that the molecular mechanism(s) underlying reduced susceptibility of CAS in the A. fumigatus strains is novel, possibly due to remodeling of the cell wall components.

Antifungal Agents↗
PubMed2005

Cytopathic changes and pro-inflammatory cytokines induced by Naegleria fowleri trophozoites in rat microglial cells and protective effects of an anti-Nfa1 antibody.

Naegleria fowleri, a free-living amoeba, causes fatal primary amoebic meningoencephalitis in experimental animals and humans. The nfa1 gene (360 bp) was previously cloned from a cDNA library of pathogenic N. fowleri by immunoscreening, and produced a 13.1-kDa recombinant protein that showed pseudopodia-specific localization by immunocytochemistry. On the basis of an idea that the pseudopodia-specific Nfa1 protein seems to be involved in the pathogenicity of N. fowleri, the cytopathic activity of N. fowleri trophozoites co-cultured with rat microglial cells was observed, and the effects of an anti-Nfa1 antibody in a co-culture system were elucidated. Using light, scanning and transmission electron microscopy, it was seen that N. fowleri trophozoites in contact with microglial cells produced vigorous pseudopodia and a food-cup structure. Microglial cells were destroyed by N. fowleri trophozoites as seen from necrotic cell death in a time-dependent manner. In a(51)Cr release assay, N. fowleri showed 17.8%, 24.9%, 54.6% and 98% cytotoxicity against microglial cells at 3, 6, 12 and 24 h post-incubation, respectively. However, when anti-Nfa1 antibody was added in a coculture system, N. fowleri cytotoxicity was reduced to 15.5%, 20.3%, 46.7% and 66.9%, respectively. Moreover, microglial cells co-cultured with N. fowleri trophozoites secreted the pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6. In the presence of anti-Nfa1 antibody, the secretion of TNF-alpha was slightly, but not significantly, decreased.

Animals↗
PubMed2005

Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates.

An association between reduced susceptibility to echinocandins and changes in the 1,3-beta-d-glucan synthase (GS) subunit Fks1p was investigated. Specific mutations in fks1 genes from Saccharomyces cerevisiae and Candida albicans mutants are described that are necessary and sufficient for reduced susceptibility to the echinocandin drug caspofungin. One group of amino acid changes in ScFks1p, ScFks2p, and CaFks1p defines a conserved region (Phe 641 to Asp 648 of CaFks1p) in the Fks1 family of proteins. The relationship between several of these fks1 mutations and the phenotype of reduced caspofungin susceptibility was confirmed using site-directed mutagenesis or integrative transformation. Glucan synthase activity from these mutants was less susceptible to caspofungin inhibition, and heterozygous and homozygous Cafks1 C. albicans mutants could be distinguished based on the shape of inhibition curves. The C. albicans mutants were less susceptible to caspofungin than wild-type strains in a murine model of disseminated candidiasis. Five Candida isolates with reduced susceptibility to caspofungin were recovered from three patients enrolled in a clinical trial. Four C. albicans strains showed amino acid changes at Ser 645 of CaFks1p, while a single Candida krusei isolate had a deduced R1361G substitution. The clinical C. albicans mutants were less susceptible to caspofungin in the disseminated candidiasis model, and GS inhibition profiles and DNA sequence analyses were consistent with a homozygous fks1 mutation. Our results indicate that substitutions in the Fks1p subunit of GS are sufficient to confer reduced susceptibility to echinocandins in S. cerevisiae and the pathogens C. albicans and C. krusei.

Amino Acid Substitution↗
PubMed2005

Two alpha(1-3) glucan synthases with different functions in Aspergillus fumigatus.

Alpha(1-3) glucan is a main component of the Aspergillus fumigatus cell wall. In spite of its importance, synthesis of this amorphous polymer has not been investigated to date. Two genes in A. fumigatus, AGS1 and AGS2, are highly homologous to the AGS genes of Schizosaccharomyces pombe, which encode putative alpha(1-3) glucan synthases. The predicted Ags proteins of A. fumigatus have an estimated molecular mass of 270 kDa. AGS1 and AGS2 were disrupted in A. fumigatus. Both Deltaags mutants have similar altered hyphal morphologies and reduced conidiation levels. Only Deltaags1 presented a reduction in the alpha(1-3) glucan content of the cell wall. These results showed that Ags1p and Ags2p were functionally different. The cellular localization of the two proteins was in agreement with their different functions: Ags1p was localized at the periphery of the cell in connection with the cell wall, whereas Ags2p was intracellularly located. An original experimental model of invasive aspergillosis based on mixed infection and quantitative PCR was developed to analyze the virulence of A. fumigatus mutant and wild-type strains. Using this model, it was shown that the cell wall and morphogenesis defects of Deltaags1 and Deltaags2 were not associated with a reduction in virulence in either mutant. This result showed that a 50% reduction in the content of the cell wall alpha(1-3) glucan does not play a significant role in A. fumigatus pathogenicity.

Amino Acid Sequence↗