Biomedical subjects

C S Lim

Publications and source records attributed to C S Lim.

At least 37 records · Page 2Linked to original sources

PubMed2001

C. elegans clk-2, a gene that limits life span, encodes a telomere length regulator similar to yeast telomere binding protein Tel2p.

An important quest in modern biology is to identify genes involved in aging. Model organisms such as the nematode Caenorhabditis elegans are particularly useful in this regard. The C. elegans genome has been sequenced [1], and single gene mutations that extend adult life span have been identified [2]. Among these longevity-controlling loci are four apparently unrelated genes that belong to the clk family. In mammals, telomere length and structure can influence cellular, and possibly organismal, aging. Here, we show that clk-2 encodes a regulator of telomere length in C. elegans.

Aging↗

PubMed2001

Size analysis of automobile soot particles using field-flow fractionation.

Soot particles emitted from various automobile engines are analyzed for size distributions using field-flow fractionation (FFF). Soot samples are prepared for FFF analysis using a three-step procedure, where a layer of soot particles is focused between the layers of n-hexane and water, followed by dispersing of particles in water containing 0.05% Triton X-100. The mean diameters determined by FFF show similar trends with those obtained from dynamic light scattering (DLS) and scanning electron microscopy (SEM). Data from FFF are also compared with those from an on-line scanning mobility particle sizer (SMPS). SMPS size distributions extend further to larger size than those of FFF distributions, which indicates the three-step sample preparation procedure effectively disaggregates the agglomerated particles. Although the amount of particulate matter (PM) emitted from a heavy-duty diesel engine is much higher than that from a light-duty diesel engine, the size distributions of soot particles show no significant difference between heavy- and light-duty diesel engines. The engine-operating mode (engine speed and load rate) does not seem to affect significantly the size distribution of soot particles. It was found that the PM from a turbocharged diesel engine contains a higher percentage of particles smaller than 100 nm than an engine with a naturally aspirated (NA) air-inhalation system. As for gasoline engines, the PM collected after the catalytic converter has a narrower size distribution than those collected before and has a higher percentage of particles smaller than 100 nm.

Air Pollution↗

PubMed2001

SPIN90 (SH3 protein interacting with Nck, 90 kDa), an adaptor protein that is developmentally regulated during cardiac myocyte differentiation.

In the yeast two-hybrid screening, we have isolated a cDNA clone from a human heart library using Nck Src homology 3 (SH3) domains as bait. The full-length cDNA, which encoded 722 amino acids, was identified as a VIP54-related gene containing an SH3 domain, proline-rich motifs, a serine/threonine-rich region, and a long C-terminal hydrophobic region. We refer to this protein as SPIN90 (SH3 Protein Interacting with Nck, 90 kDa). The amino acid sequence of the SH3 domain has the highest homology with those of Fyn, Yes, and c-Src. SPIN90 was broadly expressed in human tissues; in particular, it was highly expressed in heart, brain, and skeletal muscle, and its expression was developmentally regulated during cardiac myocyte differentiation. SPIN90 is able to bind to the first and third SH3 domains of Nck, in vitro, and is colocalized with Nck at sarcomere Z-discs within cardiac myocytes. Moreover, treatment with antisera raised against SPIN90 disrupted sarcomere structure, suggesting that this protein may play an important role in the maintenance of sarcomere structure and/or in the assembly of myofibrils into sarcomeres.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Evaluation of rapid immunocapture assays for diagnosis of Plasmodium vivax in Korea.

The rapid immunocapture assays, OptiMal and ICT, were evaluated from 87 individuals for the diagnosis of malaria infections directly from whole blood. A total of 87 individuals was examined for malaria parasites by microscopic examination of Giemsa-stained blood smears, and 65 cases were positive for Plasmodium vivax by microscopy. Correspondingly, the OptiMal test identified malaria infection in 45 cases (69.2%) of microscopy positive cases. Of these, two cases were misinterpreted as Plasmodium falciparum, whereas ICT detected P. vivax infection in 29 (44.6%) patients. We would like to propose that rapid immuno capture assays are an easy method that can serve as a useful tool in addition to microscopy for the diagnosis of malaria, but sensitivity is not yet satisfactory for diagnosis of P. vivax in Korea.

Animals↗

PubMed2001

The analysis of Plasmodium vivax Duffy receptor binding domain gene sequence from resurgent Korea isolates.

The Duffy binding domain gene structures of Plasmodium vivax facilitate the invasion of erythrocytes. Human erythrocytes that lack Duffy blood group antigens are resistant to invasion by P. vivax. We have sequenced the Duffy binding domain gene from eight P. vivax isolates collected from malaria cases in South Korea. When compared to isolates from other regions in the world, the amino acid sequences of the Korean isolates showed unique variations in region II. From 606 sequenced amino acids, 32 variations were found. Of these, three variations were regularly found in positions 424, 437 and 503 of the Sal-1 amino acid sequence. In region III, six isolates had a loss of the 30 bp (FAESTKSAE) insert. However, six isolates had 6 bp (SD) inserts at the end of region III. Two cases had a reverse pattern. Our results suggest that the P. vivax currently found in South Korea are unique when compared to other isolates and can be divided, by the analysis of their molecular structure, into two strains.

Amino Acid Sequence↗

PubMed2001

Cellular senescence, cancer and aging: the telomere connection.

Telomeres are the repetitive DNA sequences and specialized proteins that form the distinctive structure that caps the ends of linear chromosomes. Telomeres allow cells to distinguish the chromosome ends from double strand DNA breaks. The telomeric structure prevents the degradation or fusion of chromosome ends, and thus is essential for maintaining the integrity and stability of eukaryotic genomes. In addition, and perhaps less widely appreciated, telomeres may also indirectly influence gene expression. The length, structure and organization of telomeres are regulated by a host of telomere-associated proteins, and can be influenced by basic cellular processes such as cell proliferation, differentiation, and DNA damage. In mammalian cells, telomere length and/or telomere structure have been linked to both cancer and aging. Here, we briefly review what is known about mammalian telomeres and the proteins that associate with them, and discuss the cellular and organismal consequences of telomere dysfunction and the evidence that cells with dysfunctional telomeres can contribute to cancer and aging phenotypes.

Aging↗

PubMed2001

An on-belt elemental analyser for the cement industry.

On-line control of raw mill feed composition is a key factor in the improved control of cement plants. A new and improved on-conveyor belt elemental analyser for cement raw mill feed based on neutron inelastic scatter and capture techniques has been developed and tested successfully in Adelaide Brighton's Birkenhead cement plant on highly segregated material with a depth range of 100 to 180 mm. Dynamic tests in the plant have shown analyser RMS total errors of 0.49, 0.52, 0.38 and 0.23 wt% (on a loss free basis) for CaO, SiO2, Al2O3 and Fe2O3 respectively, when 10-minute counting periods are used.

Aluminum Oxide↗

PubMed2001

The analysis of circumsporozoite-protein gene sequences from South Korean isolates of Plasmodium vivax.

The amino-acid sequences corresponding to the circumsporozoite protein (CSP) of Plasmodium vivax fall into two main types, VK210 and VK247, each of which has a characteristic tandem repeat. When the repetitive domains of the CSP gene from six isolates of P. vivax from South Korea were sequenced they were found to show a total of 20 tandem amino-acid repeats, and repeat patterns that are regular and distinct from those of other P. vivax isolates. The amino-acid sequences of the South Korean parasites were found to be most similar to those of three isolates from China (CH-3, CH-4, and CH-5) and, particularly, to one from North Korea. A sequence (AGGNAANKKAEDAGGNA) and two repeats of the sequence GGNA found in the North Korean parasites were found in all six isolates from South Korea. The South Korean parasites investigated appear phylogenetically identical and unique to the Korean peninsula.

Animals↗

PubMed2001

Th1/Th2 predominance and proinflammatory cytokines determine the clinicopathological severity of IgA nephropathy.

BACKGROUND: IgA nephropathy is one of the most common forms of primary glomerulonephritis in adults. Its pathogenesis is complex. The nature of infiltrating and proliferating cells and of cellular mediators could contribute to the progression of IgA nephropathy towards end-stage renal failure. METHODS: To evaluate this hypothesis, we attempted to quantify the magnitude of intrarenal gene expression of various cytokines (IL-1 beta, TNF-alpha, IL-6, IL-15, IL-2, IFN-gamma, IL-10) and chemokines (IL-8, RANTES, MCP-1) in 48 renal core biopsy specimens, diagnosed as IgA nephropathy by immunofluorescence microscopy. Semi-quantitative reverse-transcriptase polymerase chain reaction using internal competitors was used for the quantification of gene transcripts. RESULTS: The expression of intrarenal gene transcripts of various cytokines and chemokines was closely interrelated, but not associated with the pathological grading system. The IFN-gamma/IL-10 ratio was higher in patients with renal dysfunction than in those with normal renal function (P=0.0483). Gene transcript levels of proinflammatory cytokines were related to the amount of proteinuria. In patients with severe glomerular sclerosis, the ratio of IFN-gamma/IL-10 gene transcripts was high (P=0.04). IL-10 gene transcript level was related to the severity of tubulointerstitial damage. The levels of gene expression of IL-10 (P=0.009), IFN-gamma (P=0.03), and TNF-alpha (P=0.005) were related to the degree of mesangial matrix expansion and the extent of intrarenal arteriolar changes correlated with the expression of the IL-8 gene transcript (r=0.43, P=0.004). CONCLUSIONS: We propose that Th1/Th2 predominance and the level of proinflammatory cytokines could determine the pathogenetic processes and the severity of the clinical manifestations of IgA nephropathy.

Adolescent↗

PubMed2001

Uteroglobin gene polymorphisms affect the progression of immunoglobulin A nephropathy by modulating the level of uteroglobin expression.

Uteroglobin (UG) is an anti-inflammatory/immunomodulatory protein. Targeted disruption of UG rendered mouse glomerulonephritis resembling immunoglobulin (Ig)A nephropathy (IgAN). Sequence analysis on exon 1 of UG showed several putative binding sites for transcription factors, and polymorphisms in this site might influence the expression level of UG as a competitive protein. We speculated that the single nucleotide polymorphism at the 38th nucleotide (A to G) from the transcription initiation site of UG exon 1 would impact the progression of IgA nephropathy (IgAN). Polymerase chain reaction-restriction fragment length polymorphism and single-strand conformation polymorphism were instituted to determine the genetic polymorphism. Luciferase assay was performed using the gene constructs containing a region 404-bp long located upstream of UG exon 1 initiation site to analyse whether this polymorphism would affect the expression level. UG polymorphism was distributed no differently in patients with IgAN (n = 111) compared to 60 healthy control subjects. An excess of A genotype was found in one patient having progressive disease (P = 0.03) and the risk for the disease progression increased as the number of A alleles increased (P for trend = 0.03) after follow-up for 116 months. The odds ratio for progression with the AA genotype was 4.9 (95% Cl = 1.0-23.9) compared to patients having the GG genotype. Significant interactive effects of hypertension and genetic polymorphisms of UG on the disease progression were observed (P for interaction = 0.001). In the luciferase assay, the gene construct with A at the 38th site showed a decreased activity of 74 +/- 8.4% compared to that showed by G gene construct. Our results suggest that polymorphism at the 5' UTR region of UG exon 1 is an important marker for the progression of IgAN and may modulate the level of protein expression.

5' Untranslated Regions↗

PubMed2001

Differential expression of various cytokine and chemokine genes between proliferative and non-proliferative glomerulonephritides.

BACKGROUND: Intraglomerular cellular proliferation is one of the major determinants for dividing various glomerulonephritis (GN) into two groups, such as proliferative versus non-proliferative. Cytokines and chemokines are involved in the pathogenetic pathways and would affect the functional and histologic sequelae. We hypothesized that the morphological difference might be based on the differential intrarenal expression of various cytokines and chemokines. We quantified the intrarenal gene expression of various cytokines and chemokines, and correlated it with clinical parameters. METHODS: Total RNA was extracted from 54 proliferative GN (PGN) core biopsy specimens and 42 non-proliferative GN (NPGN) specimens. Using the internal competitors, RT-PCR was instituted to quantify mRNAs. RESULTS: The magnitude of the gene expressions of IL-2, IFN-gamma, and IFN-gamma/IL-10 ratio were significantly higher in PGN than in NPGN. RANTES and IL-8 had more abundant gene messages in PGN. It was shown that Th1 cytokine was upregulated if GN was mediated by immune complexes regardless of cellular proliferation. But chemokines had the elevated levels of expression in PGN among immune complex-mediated GN. Up-regulation of the IFN-gamma/IL-10 ratio and TNF-alpha was associated with poor renal function at the time of biopsy. Renal tissues from the patients with a non-nephrotic range of proteinuria showed abundant messages for proinflammatory cytokines and chemokines. CONCLUSION: Th1, proinflammatory cytokines, and chemokines were more abundant in proliferative GN, and correlated with unfavorable clinical parameters. We propose that the clinical manifestations and diverse histologic features of human GN are associated with differential expressions of specific cytokines and chemokines.

Adolescent↗

PubMed2000

Trafficking of nuclear receptors in living cells.

Most of the steroid receptor family, with the exception of the estrogen receptor, are classically viewed as 'translocating receptors'. That is, they move from an exclusively, or principally, cytoplasmic distribution in the absence of hormone to a predominately nuclear localization in hormone stimulated cells. The estrogen receptor and the nuclear receptor family are found exclusively in the nucleus, both in hormone stimulated and hormone free cells. This behavior has now been studied with GFP-fusions in living cells, and has in general been confirmed. However, there are important exceptions, and new findings, particularly with regard to sub-nuclear localization. We propose that the intracellular distribution of both receptor classes is dependent not only on subcellular localization signals directly encoded in the receptors, but also on the nature and composition of the large, macromolecular complexes formed by each receptor. Furthermore, we find that most members of the receptor superfamily form focal accumulations within the nucleus in response to ligand, and suggest that these structures may participate in the biological life cycle of the receptors. Finally, we propose that receptor movement in the nucleus is highly dynamic, with the receptors undergoing constant exchange between genomic regulatory elements, multi-protein complexes with other transcription factor partners, and subnuclear structures that are as yet poorly defined.

Animals↗

PubMed2000

Cadaveric renal allograft at the time of implantation has the similar immunological features with the rejecting allograft.

BACKGROUND: Compared to living donations, cadaveric transplants have a poorer outcome, and the immunologic status of renal tissues at the time of transplantation might influence the final outcome of the renal allograft. PATIENTS AND METHODS: We used quantitative RT-PCR to evaluate the differential expression of cytokine genes from 37 implantation tissues [18 cadaveric tissues (CI), 19 specimens from living donors (LI)]. We compared them with 17 acutely rejecting allograft (AR). RESULTS: Acute rejection within 6 months after transplantation occurred 8 times in patients with cadaveric allograft, but the living-donor recipients experienced 4 episodes (P<0.05). Proinflammatory cytokines were co-expressed more frequently in CI than in LI. The levels of IFN-gamma, TNF-alpha and IL-10 mRNA were also higher in CI. We compared the profiles of several cytokine expressions of CI with those of AR. The messages for IL-6 were more abundant in the CI, IFN-gamma was more expressed in AR, and the other cytokine expression levels were similar in both types. However, when comparing LI and AR, all the cytokine messages except IL-6 were up-regulated in AR than in LI. In CI, the levels of cytokine gene expressions were similar despite various cold ischemic time except IL-10 that were elevated for those cases where the operation was done within 4 hr of nephrectomy. CONCLUSIONS: The numbers and levels of gene transcription of inflammatory cytokines were higher in the tissues from a cadaver, and were not different from those of AR. This immunologic hostility at the time of implantation would contribute to the poorer outcome of cadaveric allograft.

Biopsy↗

PubMed2000

Changes in chest electrode impedance.

The Prehospital Defibrillation Program in Singapore has in some cases shown a lower amplitude of ventricular fibrillation (VF) than considered the norm. The electrode skin impedance (ESI) refers to the skin impedance determined between two electrodes placed at specific positions on the body surface. The objective of this prospective study was to measure the ESI of patients at 5 Hz and 2 kHz frequencies, and assess its change with time from the application of electrodes, the difference between the ESI at two different sets of electrode placement positions, and correlation with patient factors. Patients who were 25 years or older and not critically ill had their ESI measured with a modified Heart-Save 911 defibrillator, using signal frequencies at 5 Hz and 2 kHz, at 10 seconds, 1 and 2 minutes after electrodes application. Two sets of positions were used; position 1 where an electrode is placed in the right subclavicular region and another just lateral to the apex beat on the left and position 2, which represents the mirror-image of position 1. Thirty-six each of men and women patients were studied. The mean age and weight were 59.9 +/- 13.5 years and 56.8 +/- 24.1 kg respectively. There was no significant correlation between the ESI and patients' body weight or sex. However, there was a significant decrease in the ESI with time from application of electrodes at both positions (P < .05) with the two different frequencies. The ESI was lower when measured at lower frequencies and higher when taken at higher frequencies, but there was no statistically significant difference between the two mirror-image positions used. Thus, with lower frequency, the electrocardiogram amplitude of VF recorded on the automated external defibrillator could be enhanced.

Adult↗

PubMed2000

CFD investigation of steady flow in bi-leaflet heart valve hinge.

This paper focuses on local flow patterns inside the hinge socket of a bi-leaflet mechanical heart valve (MHV), where experimental measurements are difficult due to the extremely small flow region of about 40 microm. The overall objective of this study is to simulate the steady flow in this confined micro channel within the hinge region of a partially protruded ball hinge concept. A CFD simulation of flow through a bi-leaflet heart valve hinge was carried out. Steady flow with the valve leaflet in the fully open position during the valve systole phase was studied using FLUENT 4.4.7 running on Silicon Graphics. Body Fitted Coordinates (BFC) grid distribution was applied in the overall flow domain and great care was taken at the mesh distribution within the hinge local area. The flow study focused on local flow patterns inside the hinge socket of the valve where experimental measurements in the actual size valve are not practical. CFD results show evidence of flow in local area of hinge and no evidence of stagnation. Flow migrates across the clearance, and small vortices are formed after the hinge stoppers. The results indicate that flow in the hinge region is complex and critical for the valve to function effectively.

Blood Flow Velocity↗

PubMed2000

Analysis of Plasmodium vivax merozoite surface protein-1 gene sequences from resurgent Korean isolates.

The merozoite surface protein-1 (MSP-1) of Plasmodium vivax exhibits great antigenic diversity among different isolates of this parasite. This antigen is a useful genetic marker for studying the polymorphism of natural P. vivax parasite populations. One or more of these populations has been responsible for resurgent malaria now occurring in Korea. This paper reports the analysis of a highly polymorphic region between interspecies conserved blocks 5 and 6 of the MSP-1 gene, using the polymerase chain reaction to amplify the DNA fragment encompassing these regions from 25 Korean isolates, followed by sequencing. Almost all amino acid sequences of Korean isolates were nearly identical to that of Thai isolates TD525A (96.6-99.7%) and TD424 (96.3-99.5%), and very similar to that of the France-Belem strain when compared with other isolates (Sal-1, Sri Lanka, and Colombia). Interallelic recombination was found in the poly-Q repeat and a Sal-1 type amino acid structure was observed in all isolates. This study shows that the MSP gene nucleotide sequence of resurgent P. vivax in Korea is most similar to that of Thai isolates; however, the Korean strains are phylogenetically unique.

Amino Acid Sequence↗

PubMed2000

Detection of Hantaan and Seoul viruses by reverse transcriptase-polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP) in renal syndrome patients with hemorrhagic fever.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS), also called Korean hemorrhagic fever (KHF), is the most common cause of acute renal failure in the Far East. Two serotypes of hantavirus, Hantaan and Seoul viruses are known pathogens for HFRS in Korea. PURPOSE: To elucidate the diagnostic applicability for the serotype diagnosis in HFRS patients, we used nested reverse transcriptase-PCR and restriction fragment length polymorphism (nRT-PCR/RFLP) to screen 2 prototype viruses, 11 virus isolates from HFRS patients, and 69 specimens obtained from 31 HFRS patients. METHODS: The nRT-PCR was performed using primers specific for the G1 segments of the Hantaan (HF3 1140-1163, HB14 1363-1342) and Seoul (SF2 809-832, SB3 1200-1177) viruses. The initial PCR products were then further amplified using nested primers for the Hantaan (HF4 1141-1164, HB13 1360-1339) and Seoul (SF7 863-884, SB1 1165-1142 ) viruses. Amplified segments were then digested with restriction enzymes specific for either Hantaan (C1a I) or Seoul (Sac I) virus sequences. RESULTS: In all cultured viruses, the serotypes identified by nRT-PCR/RFLP were consistent with those of PRNT. nRT-PCR/RFLP results indicated the presence of Hantaan virus in 10 patients and of Seoul virus in 15 patients. In 3 patients, both Hantaan- and Seoul-specific amplified bands were visualized in serially collected samples, and in 4 patients no amplicon was detected. Among 69 specimens, 55 were positive; these positive specimens were obtained between days 3 and days 33 of illness. The positive rate was not affected by the clinical phase, day of illness, or severity of HFRS. CONCLUSIONS: nRT-PCR/RFLP is a rapid and convenient method for serotype diagnosis in most HFRS patients. It could also allow detection of genetic variation of hantavirus within the same serotype.

Adult↗

PubMed2000

Chest impedance: characteristics of local patients.

The Pre-hospital Defibrillation Program in Singapore has in some cases demonstrated a lower amplitude of Ventricular Fibrillation (VF) than considered the norm. The Electrode Skin Impedance (ESI) refers to the skin impedance determined between two electrodes placed at specific positions on the body surface. The objective of this prospective study was to measure the ESI of patients at 5 Hz and 2 kHz frequencies, and assess its change with time from the application of electrodes, the difference between the ESI at two different sets of electrode placement positions and correlation with patient factors. Patients who were 25 years or older and not critically ill had their ESI measured with a modified Heart-Save 911 defibrillator, using signal frequencies at 5 Hz and 2 kHz, at 10 seconds, 1 and 2 minutes after electrodes application. Two sets of positions were used; Position 1 where an electrode is placed in the right infra-clavicular region and another just lateral to the apex beat on the left and Position 2, which represents the mirror image of Position 1. 36 each of male and female patients were studied. The mean age and weight were 59.9 +/- 13.5 years and 56.8 +/- 24.1 kg respectively. There was no significant correlation between the ESI and patients' body weight or sex. However, there was a significant decrease in the ESI with time from application of electrodes at both Positions (p < 0.05) with the two different frequencies. The ESI was lower when measured at lower frequencies and higher when taken at higher frequencies, but there was no statistically significant difference between the two mirror-image positions used. Thus, with lower frequency, the ECG amplitude of VF recorded on the automated external defibrillator could be enhanced.

Adult↗