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Biomedical subjects

K H Yoon

Publications and source records attributed to K H Yoon.

At least 19 recordsLinked to original sources

Design of a subcutaneous vascular access device using Ni-Ti SMA clamps for hemodialysis.

A subcutaneous vascular access device which utilizes an Ni-Ti shape memory alloy (Ni-Ti SMA) spring, has been developed as a new method for subcutaneous vascular access in the treatment of hemodialysis patients. Until now, the connection between the SVAD and needle cannot be externally monitored, and the clamp must be opened and closed with a percutaneous needle by a nephrologist. The SMA-SVAD accomplishes the opening and closing of its clamp using two Ni-Ti SMA springs, and a transcutaneous energy transmission system (TET) transmits energy to the Ni-Ti SMA springs without the need for percutaneous wires. Two SMA springs open and close the clamp of the SMA-SVAD, without affecting any of the other parts of the system. Wasted thermal energy is reduced to minimal values via electrical regional heating methods. The state of the SMA-SVAD can be monitored according to the amount of power consumed by the external energy transmitter. In in-vitro experiments, when the clamp was opened and the pressure difference in the hemodialysis machine was set to 50 mmHg, water flow through SMA-SVAD reached 500 ml/min. The maximal surface temperatures of the SVAD and catheter were successfully maintained at proper levels (approximately 38-39 degrees C), approximately 2-3 degrees higher than the temperature of the surrounding tissues. The time elapsed from the initiation of energy transmission until the opening of the SMA clamp was 5 seconds.

Catheters, Indwelling↗

Genetic polymorphisms in peroxisome proliferator-activated receptor gamma are associated with Type 2 diabetes mellitus and obesity in the Korean population.

AIMS: We examined whether the common polymorphisms of the peroxisome proliferator-activated receptor-gamma (PPARgamma) gene are associated with Type 2 diabetes or obesity in the Korean population. METHODS: We genotyped two common PPARgamma polymorphisms (Pro12Ala and 161C > T) and examined their association with the clinical phenotypes found in 684 patients with Type 2 diabetes mellitus and 291 non-diabetic control subjects. RESULTS: The 12Ala allele was less frequent in the Type 2 diabetic patients than in the non-diabetic control subjects (0.036 vs. 0.053, P = 0.024). The allele frequencies of the 161C > T polymorphism did not differ between the control and Type 2 diabetic group (0.158 vs. 0.173). In the non-diabetic controls, those with the T allele had lower BMI and fasting serum triglyceride (TG) concentrations than those with the C/C homozygote (22.7 +/- 2.9 vs. 23.8 +/- 3.2 kg/m2, P = 0.002; 1.45 +/- 0.81 vs. 1.65 +/- 0.83 mmol/l, P = 0.03, respectively). The 12Ala-161T haplotype was associated with a decreased risk for Type 2 diabetes (OR = 0.47, P = 0.009), whereas the 12Pro-161T haplotype was associated with lower BMI and lower fasting serum TG (22.5 +/- 2.8 vs. 23.7 +/- 3.2 kg/m2, P = 0.004; 1.41 +/- 0.87 vs. 1.64 +/- 0.79 mmol/l, P = 0.02, respectively). CONCLUSIONS: The PPARgamma 12Ala allele was associated with a reduced risk of Type 2 diabetes, whereas the PPARgamma 161T allele was associated with lower BMI and fasting serum TG concentrations in the Korean subjects. The subjects with 12Ala-161T haplotypes had a reduced risk of Type 2 diabetes.

Alleles↗

Magnetic resonance imaging and diffusion-weighted imaging changes after hypoglycemic coma.

The authors report a case of severe hypoglycemic encephalopathy in an elderly patient. The magnetic resonance images showed bilateral cortical signal changes and basal ganglia lesions, which spared the thalami. The lesions were bright on fluid-attenuated inversion recovery and diffusion-weighted images and dark on the apparent diffusion coefficient map, being more conspicuous on the diffusion-weighted images than on the fluid-attenuated inversion recovery images. A literature review of the imaging features and pathophysiological mechanism in comparison with those of hypoxic ischemic injury is discussed.

Aged↗

Total knee arthroplasty in stiff knees after previous infection.

Between July 1986 and August 1996, we performed 32 total knee arthroplasties (TKA) on 32 patients with partially or completely ankylosed knees secondary to infection. Their mean age at surgery was 40 years (20 to 63) and the mean follow-up was ten years (5 to 13). The mean post-operative range of movement was 75.3 degrees (30 to 115) in those with complete and 98.7 degrees (60 to 130) in those with partial ankylosis. The mean Hospital for Special Surgery knee score increased from 57 to 86 points post-operatively. There were complications in four knees (12.5%), which included superficial infection (one), deep infection (one), supracondylar femoral fracture (one) and transient palsy of the common peroneal nerve (one). Although TKA in the ankylosed knee is technically demanding and has a considerable rate of complications, reasonable restoration of function can be obtained by careful selection of patients, meticulous surgical technique, and aggressive rehabilitation.

Adult↗

Transcription factor decoy for AP-1 reduces mesangial cell proliferation and extracellular matrix production in vitro and in vivo.

Diabetic nephropathy is characterized by an expansion of glomerular mesangium, caused by mesangial cell proliferation and excessive accumulation of extracellular matrix (ECM) proteins, which eventually leads to glomerulosclerosis and renal failure. Activator protein-1 (AP-1), a transcription factor, is implicated in the transcriptional regulation of a wide range of genes participating in cell proliferation and ECM production. This investigation was undertaken to test the hypothesis that AP-1 plays an important role in ECM gene expression, and to develop a molecular therapeutic strategy based on decoy oligodeoxynucleotides (ODN). In this report, we show that transfection with AP-1 decoy ODN strongly inhibits high glucose- and angiotensin II-induced cell proliferation and expression of ECM genes in cultured mesangial cells in vitro. Administration of AP-1 decoy ODN into streptozotocin-induced diabetic rat kidney in vivo using the hemagglutinating virus of Japan (HVJ)-liposome method virtually abolished TGF-beta1 and plasminogen activator inhibitor-1 expression. Our results collectively indicate that AP-1 activation is crucial for mesangial cell proliferation and ECM production in response to high glucose and angiotensin II. Moreover, use of stable AP-1 decoy ODN combined with the highly effective HVJ-liposome method provides a novel potential molecular therapeutic strategy for the prevention of diabetic nephropathy.

Angiotensin II↗

Expression of the intermediate filament vimentin in proliferating duct cells as a marker of pancreatic precursor cells.

OBJECTIVES: The expression of the intermediate filament (IF) vimentin, usually considered a marker of mesenchymal cells, has been observed in the epithelial cells during embryogenesis, carcinogenesis, and dedifferentiation, suggesting that it might be useful as a marker of proliferating precursor cells in the pancreas. METHODS: Rat pancreata at E18 and at different time points after partial pancreatectomy (Px) and human and neonatal pig pancreatic tissue sections and monolayer cultured pancreatic duct cells were observed. All tissues were simultaneously immunostained with pancytokeratin and vimentin antibodies. In costained duct cells, PDX-1 or PCNA expression was also analyzed using confocal microscope images. RESULTS: In the rat embryonic pancreas at E18, all epithelial cells that formed ductlike structures expressed both cytokeratin and vimentin IF, whereas no duct cells costained for IF in the adult rat or neonatal pig pancreas. Such costaining reappeared in the following order: common pancreatic duct, main ducts, foci of regeneration and then disappeared completely at 30 days after Px. In humans, costaining was found in only 1 diabetic patient's pancreatic section, which was accompanied by massive duct cell proliferation. In monolayer culture, most of the duct cells of human and neonatal pigs coexpressed both IF proteins. Only a few costained duct cells also expressed PDX-1, and most of those cells were also stained with PCNA in rat embryonic pancreas and regenerating foci after partial Px. CONCLUSIONS: Vimentin IF expression might be a useful marker for pancreatic precursor cells and could be used to investigate the concept of the dedifferentiation of fully matured duct cells during the process of the beta-cell neogenesis.

Animals↗

Validity and reliability of the EQ-5D self-report questionnaire in English-speaking Asian patients with rheumatic diseases in Singapore.

Validity and reliability of a Singaporean English EQ-5D self-report questionnaire (EQ-5D) were evaluated among consecutive outpatients with rheumatic diseases attending a tertiary referral hospital in Singapore (a multi-ethnic, urban Asian country). Subjects were interviewed twice within a 2-week period using a standardized questionnaire containing the EQ-5D, Short Form 36 Health Survey (SF-36) and assessing demographic and psychosocial characteristics. To assess validity of the EQ-5D, 13 hypotheses relating responses to EQ-5D dimension/Visual Analogue Scale (EQ-VAS) to SF-36 scores or other variables were examined using the Mann-Whitney test, Kruskal-Wallis test, or Spearman's correlation coefficient. Test-retest reliability was assessed using Cohen's kappa. Sixty-six subjects were studied (osteoarthritis: 9, rheumatoid arthritis: 26, systemic lupus erythematosus: 23, spondyloarthropathy: 8; female: 72.7%; mean age: 44.3 years). Ten of 13 a-priori hypotheses relating EQ-5D responses to external variables were fulfilled, supporting the validity of the EQ-SD. Cohen's kappa for test-retest reliability (n = 52) ranged from 0.29 to 0.61. The Singaporean English EQ-5D appears to be valid in measuring quality of life in Singaporeans with rheumatic diseases; however, its reliability requires further investigation. These data provide a basis for further studies assessing the validity of the EQ-5D in Singapore.

Adolescent↗

Single-nucleotide polymorphisms of the interleukin-18 gene promoter region in rheumatoid arthritis patients: protective effect of AA genotype.

Rheumatoid arthritis (RA) is a chronic arthritic condition that can lead to deformities and disabilities. Although numerous studies reported the association of human leukocyte antigen (HLA)-DRB1*04 and RA, other genes, e.g. cytokines genes, may contribute towards disease susceptibility. Interleukin-18 (IL-18) is a proinflammatory cytokine postulated to play a role in the acute and chronic inflammatory phases of RA. The IL-18 protein expression seems to be regulated by two single-nucleotide polymorphisms (SNPs) located at positions -607 and -137 in the promoter region of the gene. It is postulated that specific alleles may be associated with susceptibility to the development of RA. In the present study, we described the IL-18 gene promoter region genotypes and combined genotypes (-607/-137) in 106 RA patients and 273 unrelated healthy controls to evaluate the contributions of these alleles to RA predisposition in Chinese, Malays, and Indians. The genotyping were performed using sequence-specific polymerase chain reactions. Rheumatoid factors were assayed by enzyme-linked immunosorbent assay. Biodata were obtained through chart review. The controls had significantly higher frequency of AA genotype at position -607 when compared to RA patients. No significant differences were observed in the distribution of either allelic or genotypic frequencies at position -137. There was no association between the genotypes and the presence of rheumatoid factors. This study did not find evidence of a genetic susceptibility factor but demonstrated the novel finding that the AA genotype at position -607 is associated with a protective effect against development of RA in Chinese individuals. This protection may be mediated through inhibition of cyclic (Adenosine 3', 5'-cyclic monophosphate) AMP-responsive element (CRE)-binding protein by the disruption of the CRE consensus sequence.

Adult↗

High prevalence of antiphospholipid antibodies in Asian cancer patients with thrombosis.

Thrombotic complications are a significant cause of morbidity and mortality in cancer patients. Studies in Caucasian populations have shown that up to one-third of such patients test positive to antiphospholipid antibodies. Our aim was to determine the prevalence and serotypes of antiphospholipid antibodies in an unselected group of Asian cancer patients with thrombosis. All patients with cancer-related thrombosis seen in the Department of Hematology-Oncology and Radiation Oncology were enrolled in this study. The study period was from April 2000 to May 2001. Antiphospholipid antibodies tests were performed, namely lupus anticoagulant screen, anticardiolipin antibodies (IgG and IgM) and anti-beta-2 glycoprotein I antibodies (B2 GPI) IgG, IgM and IgA. Thirty-three patients were recruited. There were 14 males and 19 females, with an age range of 35-78 years of age. Of those enrolled, there were 25 Chinese, five Malays and three Indians. The patients had several cancer types: 11 (36.7%) patients had adenocarcinoma as the histological cell type. Of the 33 patients, 75.8% had stage IV disease. Arterial thrombosis was seen in eight patients (24.2%), and venous thrombosis occurred in 29 patients (87.9%). Antiphospholipid antibodies were positive in 60.6% of the patients, of which anti-B2GPI IgA antibody was the most prevalent antiphospholipid present (46.9%). The presence of anti-beta-2 glycoprotein I IgA antibody was associated with strokes, extensive and recurrent venous thrombosis, and coincident arterial and venous thrombosis. A high prevalence of antiphospholipid antibodies (60.6%) was found in Asian patients with cancer-related thrombosis. The presence of antiphospholipid antibodies, particularly anti B2GPI IgA, may identify a subset of cancer patients who are at high risk of developing thrombotic complications, and further studies are warranted.

Adenocarcinoma↗

Validity and reliability of the EQ-5D self-report questionnaire in Chinese-speaking patients with rheumatic diseases in Singapore.

OBJECTIVE: We assessed the psychometric properties of a Singaporean Chinese version of the EQ-5D, a health-related quality of life (HRQoL) instrument. MATERIALS AND METHODS: Consecutive outpatients with rheumatic diseases seen for routine follow-up consultations at the National University Hospital, Singapore were interviewed twice within 2 weeks using a standardised questionnaire containing the EQ-5D, the Short-Form 36 Health Survey (SF-36), the Learned Helplessness Subscale, a pain Visual Analogue Scale (VAS) and assessing demographic and psychosocial characteristics. To assess the validity of the EQ-5D, 13 hypotheses relating the EQ-5D self-classifier (5 dimensions) or visual analogue scale (EQ-VAS) to SF-36 scores or other variables were examined using the Mann-Whitney U test, Kruskal-Wallis or Spearman's correlation coefficient. Test-retest reliability was assessed using Cohen's kappa. RESULTS: Forty-eight subjects were studied (osteoarthritis: 16; rheumatoid arthritis: 22; systemic lupus erythematosus: 8; spondyloarthropathy: 2; female: 93.8%; mean age: 56.4 years). Seven of 13 a-priori hypotheses relating EQ-5D to external variables were fulfilled, supporting the validity of the EQ-5D. For example, subjects reporting moderate or extreme problems for EQ-5D dimensions generally had lower median SF-36 scores than those without such problems. Cohen's kappa for test-retest reliability of the self-classifier ranged from 0.41 to 1.00 (n = 42; median interval: 7 days, interquartile range: 7 to 11 days). CONCLUSIONS: The Singaporean Chinese EQ-5D self-classifier appears to be a valid measure of HRQoL in Singaporeans with rheumatic diseases; however, the reliability of the EQ-VAS requires further investigation. These data provide a basis for further studies of the Singaporean Chinese EQ-5D.

Activities of Daily Living↗

Melasma: histopathological characteristics in 56 Korean patients.

BACKGROUND: Melasma is a common acquired symmetrical hypermelanosis characterized by irregular light to dark brown macules and patches on sun-exposed areas of the skin. Its histopathological characteristics are not fully understood. OBJECTIVES: To characterize the histopathological features of facial melasma skin in comparison with adjacent normal skin. METHODS: Biopsies were taken from both melasma lesional skin and adjacent perilesional normal skin in 56 Korean women with melasma. The sections were stained using haematoxylin and eosin, Fontana-Masson, diastase-resistant periodic acid-Schiff, Masson trichrome and Verhoeff-van Gieson stains, and immunostaining for melanocytes. Data on the changes in number of melanocytes and melanin contents of the epidermis were analysed by a computer-assisted image analysis program. The ultrastructure of the skin was also examined. RESULTS: The amount of melanin was significantly increased in all epidermal layers in melasma skin. The staining intensity and number of epidermal melanocytes increased in melasma lesions. Lesional skin showed more prominent solar elastosis compared with normal skin. Melanosomes increased in number and were more widely dispersed in the keratinocytes of the lesional skin. Lesional melanocytes had many more mitochondria, Golgi apparatus, rough endoplasmic reticulum and ribosomes in their cytoplasm. A dihydroxyphenylalanine reaction was apparent in the cisternae and vesicles of the trans-Golgi network in melanocytes from lesional skin. CONCLUSIONS: Melasma is characterized by epidermal hyperpigmentation, possibly caused both by an increased number of melanocytes and by an increased activity of melanogenic enzymes overlying dermal changes caused by solar radiation.

Adult↗

Insights into the dynamic properties of keratin intermediate filaments in living epithelial cells.

The properties of keratin intermediate filaments (IFs) have been studied after transfection with green fluorescent protein (GFP)-tagged K18 and/or K8 (type I/II IF proteins). GFP-K8 and -K18 become incorporated into tonofibrils, which are comprised of bundles of keratin IFs. These tonofibrils exhibit a remarkably wide range of motile and dynamic activities. Fluorescence recovery after photobleaching (FRAP) analyses show that they recover their fluorescence slowly with a recovery t(1/2) of approximately 100 min. The movements of bleach zones during recovery show that closely spaced tonofibrils (<1 microm apart) often move at different rates and in different directions. Individual tonofibrils frequently change their shapes, and in some cases these changes appear as propagated waveforms along their long axes. In addition, short fibrils, termed keratin squiggles, are seen at the cell periphery where they move mainly towards the cell center. The motile properties of keratin IFs are also compared with those of type III IFs (vimentin) in PtK2 cells. Intriguingly, the dynamic properties of keratin tonofibrils and squiggles are dramatically different from those of vimentin fibrils and squiggles within the same cytoplasmic regions. This suggests that there are different factors regulating the dynamic properties of different types of IFs within the same cytoplasmic regions.

Animals↗

Early onset methotrexate-induced pancytopenia and response to G-CSF: a report of two cases.

Methotrexate (MTX) is one of the most widely used antirheumatic drugs for the treatment of rheumatoid arthritis. Whereas the hepatotoxicity of methotrexate is well recognized, the hematologic toxicity, namely, pancytopenia, is still a concern and is potentially fatal. We report two cases of early-onset methotrexate-induced pancytopenia that were successfully treated with granulocyte colony-stimulating factor (G-CSF). The pancytopenia improved with 3 days of administration. A review of the literature revealed at least 146 reported cases of MTX-induced pancytopenia. Significant risk factors for myelotoxicity included renal impairment, infection, and hypoalbuminemia. Successful management includes prompt discontinuation of MTX, intravenous folinic acid, high-dose steroids and, as in our case, G-CSF.

Journal Article↗

Hypodipsic hypernatremia with intact AVP response to non-osmotic stimuli induced by hypothalamic tumor: a case report.

Anatomical lesions of hypothalamic area associated with hypodipsic hypernatremia have been reported only rarely. We report here a case of hypodipsic hypernatremia induced by a hypothalamic lesion. A 25-yr-old man, who had been treated with radiation for hypothalamic tumor 5-yr before, was admitted for evaluation of hypernatremia and hypokalemia. He never felt thirst despite the elevated plasma osmolality and usually refused to drink intentionally. Plasma arginine vasopressin (AVP) level was normal despite the severe hypernatremic hyperosmolar state and urine was not properly concentrated, while AVP secretion was rapidly induced by water deprivation and urine osmolality also progressively increased to the near maximum concentration range. All of these findings were consistent with an isolated defect in osmoregulation of thirst, which was considered as the cause of chronic hypernatremia in the patient without an absolute deficiency in AVP secretion. Hypokalemia could be induced by activation of the renin-angiotensin-aldosterone system as a result of volume depletion. However, inappropriately low values of plasma aldosterone levels despite high plasma renin activity could not induce symptomatic hypokalemia and metabolic alkalosis. The relatively low serum aldosterone levels compared with high plasma renin activity might result from hypernatremia. Hypernatremia and hypokalemia were gradually corrected by intentional water intake only.

Adult↗

The effect of cilostazol on glucose tolerance and insulin resistance in a rat model of non-insulin dependent diabetes mellitus.

BACKGROUND: It has been reported that many peripheral vasodilating drugs might improve insulin resistance. Cilostazol, a antithrombotic agent, increases peripheral blood flow in non-insulin dependent diabetic patients. The effect of cilostazol treatment on insulin resistance in streptozotocin (STZ)-induced non-insulin dependent diabetic Wistar rats was examined. METHODS: About a half of two-day old neonate siblings were injected intraperitoneally with STZ and maintained for six months, at which time they were compared with age-matched control rats for intraperitoneal glucose tolerance test (IPGTT) and for glucose infusion rate (GINF) in a euglycemic hyperinsulinemic glucose-clamp study. After that, these studies were also performed after feeding rat chow containing cilostazol (100 mg/kg/day) to rats with STZ-induced non-insulin dependent diabetes mellitus for four-weeks and compared with those of age-matched control rats. RESULTS: In the intraperitoneal glucose tolerance test studies, plasma glucose levels of STZ-induced non-insulin dependent diabetic rats were significantly higher and plasma insulin levels significantly lower than those of age-matched control rats in the age of six months. Glucose infusion rate was lower in STZ-induced non-insulin dependent diabetic rats than those of age-matched control rats. However, after a four-week cilostazol treatment, glucose infusion rate of STZ-induced non-insulin dependent diabetic rats was not significantly different from that of control rats. CONCLUSION: These findings suggested that cilostazol may improve insulin resistance in STZ-induced non-insulin dependent diabetic rats.

Animals↗

Domain III function of Mu transposase analysed by directed placement of subunits within the transpososome.

Assembly of the functional tetrameric form of Mu transposase (MuA protein) at the two att ends of Mu depends on interaction of MuA with multiple att and enhancer sites on supercoiled DNA, and is stimulated by MuB protein. The N-terminal domain I of MuA harbours distinct regions for interaction with the att ends and enhancer; the C-terminal domain III contains separate regions essential for tetramer assembly and interaction with MuB protein (IIIalpha and IIIbeta, respectively). Although the central domain II (the 'DDE' domain) of MuA harbours the known catalytic DDE residues, a 26 amino acid peptide within IIIalpha also has a non-specific DNA binding and nuclease activity which has been implicated in catalysis. One model proposes that active sites for Mu transposition are assembled by sharing structural/catalytic residues between domains II and III present on separate MuA monomers within the MuA tetramer. We have used substrates with altered att sites and mixtures of MuA proteins with either wild-type or altered att DNA binding specificities, to create tetrameric arrangements wherein specific MuA subunits are nonfunctional in II, IIIalpha or IIIbeta domains. From the ability of these oriented tetramers to carry out DNA cleavage and strand transfer we conclude that domain IIIalpha or IIIbeta function is not unique to a specific subunit within the tetramer, indicative of a structural rather than a catalytic function for domain III in Mu transposition.

Amino Acids↗