Biomedical subjects

J Kwon

Publications and source records attributed to J Kwon.

At least 19 recordsLinked to original sources

PubMed2006

Risk factors for dietary variety decline among Japanese elderly in a rural community: a 8-year follow-up study from TMIG-LISA.

OBJECTIVE: To examine the factors related to the decline of dietary variety among the rural community-dwelling Japanese elderly people and the implication on the planning of elderly people's nutritional improvement program in the future. DESIGN: A prospective cohort study during 8-year follow-up from 1992 to 2000. SETTING: This study was conducted in Nangai Village, a rural and mainly agricultural area of Akita Prefecture in the northern part of Honshu, one of four main islands in Japan. SUBJECTS: A total of 417 elderly people (160 men, 257 women) who completed interviews and food intake frequency surveys conducted in 1992, 1994, 1996, 1998, and 2000 were studied. METHODS: Dietary variety and variables potentially associated with dietary variety decline were identified from a face-to-face interview at the baseline and 8-year follow-up surveys. The dietary variety was measured using the dietary variety score (DVS), which covers the 10 main food groups in Japanese meals. RESULTS: During the 8-year follow-up, 36.2% of the subjects showed a decline in dietary variety. Health characteristics also change among the 8-year follow-up and these changes have an effect on the decline of dietary variety. Significant predictors for decline in dietary variety included loss of spouse, deterioration in self-perceived chewing ability, and decrease in intellectual activity score. CONCLUSIONS: Loss of spouse, deterioration in chewing ability, and decline in intellectual activity may increase the risk of decline in dietary variety in community-dwelling Japanese elderly people.

Activities of Daily Living↗

PubMed2005

Localization of ubiquitin carboxyl-terminal hydrolase-L1 in cynomolgus monkey placentas.

Ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) is a restrictedly expressed enzyme in neural and reproductive tissues, and it is considered to have a significant role in reproduction. In the present study, we investigated the localization of UCH-L1 in placenta of cynomolgus monkeys (Macaca fascicularis). UCH-L1 protein was detected in cytotrophoblasts of chorionic plate and villi, and decidual cells of decidua basalis in cynomolgus monkey placenta, and the amount of UCH-L1 protein in whole placenta increased as pregnancy progressed. These results supported that UCH-L1 is necessary for placental and fetal development in primate placenta. This is the first report to demonstrate the presence of UCH-L1 in primate placenta, and the cynomolgus monkey may be a useful model for the study of the functions of the ubiquitin-proteasome system in human pregnancy.

Animals↗

PubMed2005

Functional group characterization of indoor, outdoor, and personal PM: results from RIOPA.

UNLABELLED: Fourier transform infrared (FTIR) spectra of outdoor, indoor, and personal fine particulate matter (PM(2.5)) samples were collected during the Relationship of Indoor, Outdoor, and Personal Air (RIOPA) study. FTIR spectroscopy provides functional group information about the entire PM(2.5) sample without any chemical preparation. It is particularly important to characterizing the poorly understood organic fraction of PM(2.5). To our knowledge this is the first time that FTIR spectroscopy has been applied to a PM(2.5) exposure study. The results were used to chemically characterize indoor air and personal exposure. Sulfate was strongest in outdoor samples, which is consistent with the generally accepted understanding that sulfate is of outdoor origin. Absorbances attributed to soil dust were also seen in many outdoor and some indoor and personal samples. Inorganic nitrate absorbances were a common feature of many California and some New Jersey samples. Carbonyl absorbances showed substantial variation in strength, number of peaks, and wave number shift between samples, indicating variability in composition and sources. Absorbances attributed to aliphatic hydrocarbon and amide functional groups were enhanced in many personal and indoor samples, which suggested the influence of indoor sources in these homes. We speculate that meat cooking is one possible source of particulate amides. PRACTICAL IMPLICATIONS: To our knowledge this is the first time that FTIR spectroscopy has been used to characterize the composition of indoor and personal PM(2.5). The presence of sulfate, nitrate, ammonium, soil dust and a number of organic functional groups are all detected in one analysis on filter samples without extraction or other sample preparation. Differences between indoor and outdoor spectra are used to identify spectral features due to indoor-generated PM(2.5). Particularly interesting are the much larger aliphatic absorbances, shifts in carbonyl absorbances, and occasional small amide absorbances found in indoor and personal spectra but rarely in outdoor spectra. These observations are important because organics make up a large portion of PM(2.5) mass and their composition and properties are poorly characterized. The properties and behavior of organic compounds in airborne particles are often predicted based on their functional group composition. This analysis begins the development of a better understanding of the functional group composition of indoor and personal PM(2.5) and how it differs from that of outdoor PM(2.5). Eventually this will lead to an improved understanding of the properties, behavior and effects of PM(2.5) of indoor and outdoor origin.

Air Pollutants↗

PubMed2004

Optimal management for surgically Stage 1 serous cancer of the uterus.

OBJECTIVE: To describe the outcomes of patients who have undergone well-conducted surgery and found to have Stage 1 serous uterine cancer. METHODS: This retrospective cohort study includes women who have been treated for Stage 1 serous cancer of the uterus from 1985 to 2001. Cases were included from the regional cancer centers in Hamilton, London, Sunnybrook Toronto and Cancer Care Manitoba. RESULTS: Forty-three women met the inclusion criteria: Complete surgical staging (n = 27), surgery followed by pelvic radiation therapy (n = 4), surgery followed by whole abdominal radiation therapy (n = 6), surgery followed by adjuvant chemotherapy (n = 6). Patient age or depth of invasion did not influence survival. Progression free interval was 22 months (SD = 14.29). Recurrence rate was highest for adjuvant chemotherapy (66%). Survival was assessed by treatment modality and a statistically significant poorer survival was seen in the adjuvant chemotherapy group (OR 17.5; 95% CI 1.3-227.6). No comment can be made on a superior treatment regimen given the small numbers in each treatment strata. CONCLUSION: This study supports the findings of others in the literature. In a group of patients where surgical staging shows limited disease (i.e., surgically Stage 1 disease), then surgery alone appears to be adequate treatment.

Aged↗

PubMed2003

T cell receptor-stimulated generation of hydrogen peroxide inhibits MEK-ERK activation and lck serine phosphorylation.

Previous studies indicated that antigen receptor (TcR) stimulation of mature T cells induced rapid generation of reactive oxygen species (ROS). The goal of the current study was to examine the role(s) of ROS in TcR signal transduction, with a focus upon the redox-sensitive MAPK family. TcR cross-linking of primary human T blasts and Jurkat human T cells rapidly activated the ERK, JNK, p38 and Akt kinases within minutes, and was temporally associated with TcR-stimulated production of hydrogen peroxide (H(2)O(2)). TcR-induced activation of ERK was selectively augmented and sustained in the presence of pharmacologic antioxidants that can quench or inhibit H(2)O(2) production (NAC, MnTBAP and Ebselen, but not DPI), while activation of JNK and Akt were largely unaffected. This was paralleled by concurrent changes in MEK1/2 phosphorylation, suggesting that ROS acted upstream of MEK-ERK activation. Molecular targeting of H(2)O(2) by overexpression of peroxiredoxin II, a thioredoxin dependent peroxidase, also increased and sustained ERK and MEK activation upon TcR cross-linking. Enhancement of ERK phosphorylation by antioxidants correlated with increased and sustained serine phosphorylation of the src-family kinase lck, a known ERK substrate. Thus, the data suggest that TcR-stimulated production of hydrogen peroxide negatively feeds back to dampen antigen-stimulated ERK activation and this redox-dependent regulation may serve to modulate key steps in TcR signaling.

Antioxidants↗

PubMed2001

Tsetse immune responses and trypanosome transmission: implications for the development of tsetse-based strategies to reduce trypanosomiasis.

Tsetse flies are the medically and agriculturally important vectors of African trypanosomes. Information on the molecular and biochemical nature of the tsetse/trypanosome interaction is lacking. Here we describe three antimicrobial peptide genes, attacin, defensin, and diptericin, from tsetse fat body tissue obtained by subtractive cloning after immune stimulation with Escherichia coli and trypanosomes. Differential regulation of these genes shows the tsetse immune system can discriminate not only between molecular signals specific for bacteria and trypanosome infections but also between different life stages of trypanosomes. The presence of trypanosomes either in the hemolymph or in the gut early in the infection process does not induce transcription of attacin and defensin significantly. After parasite establishment in the gut, however, both antimicrobial genes are expressed at high levels in the fat body, apparently not affecting the viability of parasites in the midgut. Unlike other insect immune systems, the antimicrobial peptide gene diptericin is constitutively expressed in both fat body and gut tissue of normal and immune stimulated flies, possibly reflecting tsetse immune responses to the multiple Gram-negative symbionts it naturally harbors. When flies were immune stimulated with bacteria before receiving a trypanosome containing bloodmeal, their ability to establish infections was severely blocked, indicating that up-regulation of some immune responsive genes early in infection can act to block parasite transmission. The results are discussed in relation to transgenic approaches proposed for modulating vector competence in tsetse.

Amino Acid Sequence↗

PubMed2001

Dichloroacetate exerts therapeutic effects in transgenic mouse models of Huntington's disease.

Dichloroacetate (DCA) stimulates pyruvate dehydrogenase complex (PDHC) activity and lowers cerebral lactate concentrations. In the R6/2 and N171-82Q transgenic mouse models of Huntington's disease (HD), DCA significantly increased survival, improved motor function, delayed loss of body weight, attenuated the development of striatal neuron atrophy, and prevented diabetes. The percentage of PDHC in the active form was significantly reduced in R6/2 mice at 12 weeks of age, and DCA ameliorated the deficit. These results provide further evidence for a role of energy dysfunction in HD pathogenesis and suggest that DCA may exert therapeutic benefits in HD.

Animals↗

PubMed2001

Clinical dietetics changes due to cost-reduction activities in healthcare systems.

OBJECTIVE: This study was designed to assess changes in clinical dietetics due to cost-reduction activities in healthcare systems. SUBJECTS: 1,200 ADA members who indicated that they were employed by acute care hospitals in ADA Area 2 states. DESIGN: A questionnaire about changes in clinical dietetics staffing and clinical dietitians' activities and responsibilities was developed based on qualitative research. Descriptive statistics, t tests, analysis of variance, chi2 tests, and correlations were calculated. RESULTS: A total of 342 usable questionnaires (28.5%) were returned. More than one third (37.9%) of respondents reported reductions in the number of clinical dietitians, and 32.2% reported increases in the number of part-time clinical dietitians. Most respondents indicated that they were more involved with high-risk patient interventions, had limited time for inpatient instruction, and experienced an increased patient caseload. Although 45.4% of respondents reported diminished job satisfaction due to recent changes in healthcare systems, some changes, such as increased high-risk patient intervention and referrals, were positively correlated with perceived job satisfaction. DISCUSSION: Thorough review of current clinical dietetics activities/responsibilities and planning before cost-reduction, restructuring activities may maximize staff utilization without decreased job satisfaction of clinical dietetics staff.

Clinical Competence↗

PubMed2001

Characterization of genes expressed in the salivary glands of the tsetse fly, Glossina morsitans morsitans.

Salivary gland products of haematophogous insects including tsetse flies (Diptera: Glossinidia) are involved in antihaemostasis to allow for efficient blood feeding. In addition, salivary products of tsetse are thought to indirectly support the metacyclogenesis and eventual transmission of the African trypanosome protozoan parasites to their mammalian hosts. We have previously characterized the major anticoagulant, Tsetse Thrombin Inhibitor (TTI), from salivary extracts, and described molecular aspects of its cDNA from a Glossina morsitans morsitans salivary gland cDNA library. In addition, a family of two related genes with growth factor and adenosine-deaminase motifs (TSGF-1 and TSGF-2) have also been described. Here, we report on the molecular aspects of three different cDNAs and their putative products expressed in salivary glands: cDNAs TAg5, Tsal1 and Tsal2. The full-length transcript encoded by Tsetse Antigen 5 (TAg5) cDNA is 926 bp excluding the poly(A) stretch, and has an open reading frame of 259 amino acids that can encode for a protein of 28 925 Da. The putative product of TAg5 shows extensive similarities to cDNAs characterized from Drosophila (Agr and Agr2) and sandfly Lutzomyia (LuLoAG5). The cDNAs Tsal1 and Tsal2 are predicted to encode for mature proteins of 45 612 Da (399 amino acids) and 43 930 Da (389 amino acids), respectively, and their putative products exhibit over 42% identity to one another. The N terminus of each putative protein contains a hydrophobic region with signal peptide characteristics indicating that they may be secretory in nature. Transcripts specific for TAg5 and Tsal2 genes can be detected in all developmental stages of tsetse while Tsal1 expression is limited to adult and larval stages. A reverse transcription polymerase chain reaction based amplification approach indicates that TAg5 transcipts can be detected from proventriculus and midgut tissues of the fly in addition to salivary glands, while Tsal1 and Tsal2 expression is restricted to salivary gland and proventriculus. The salivary glands of adult males are found to express higher levels of TAg5 and Tsal2 in comparison to females while no significant sex-based difference is observed for Tsal1 expression. The expression of these cDNAs in different tsetse species (G. m. morsitans, Glossina austeni and Glossina fuscipes) shows wide variations.

Amino Acid Sequence↗

PubMed2001

Preoperative concurrent chemoradiotherapy for stage IIIA non-small cell lung cancer.

Thirty-one patients with stage IIIA non-small cell lung cancer (NSCLC) were treated with preoperative concurrent chemoradiotherapy (CCRT) followed by surgery. The treatment protocol could not be completed in eight patients. The acute hematologic toxicities of grade III or IV occurred in 48.4%, (15/31) after the first chemotherapy cycle, and in 39.1% (9/23) after the second cycle. The most common non-hematologic toxicity was radiation esophagitis. Surgery was attempted in 23 patients and successful in 22 patients (resection rate = 71.0%. Pathologic complete response and down-staging were achieved in 13.6% (3/22) and 68.2% (15/22). The median survival period, 2-year overall survival, local control and disease-free survival rates of all 31 patients and of 22 patients who underwent surgery were 19 months, 37.2%, 49.1%, 35.5%, and 19 months, 43.2%, 51.8%, 25.6%, respectively. On the basis of our observations, preoperative CCRT followed by surgery for stage IIIA NSCLC has resulted in outcomes comparable with those in previous reports.

Adult↗

PubMed2000

Susceptibility locus for Alzheimer's disease on chromosome 10.

The apolipoprotein E (APOE) gene is the only genetic risk factor that has so far been linked to risk for late-onset Alzheimer's disease (LOAD). However, 50 percent of Alzheimer's disease cases do not carry an APOE4 allele, suggesting that other risk factors must exist. We performed a two-stage genome-wide screen in sibling pairs with LOAD to detect other susceptibility loci. Here we report evidence for an Alzheimer's disease locus on chromosome 10. Our stage one multipoint lod score (logarithm of the odds ratio for linkage/no linkage) of 2.48 (266 sibling pairs) increased to 3.83 in stage 2 (429 sibling pairs) close to D10S1225 (79 centimorgans). This locus modifies risk for Alzheimer's disease independent of APOE genotype.

Age of Onset↗

PubMed2000

Hydrogen peroxide: a key messenger that modulates protein phosphorylation through cysteine oxidation.

Ligand-receptor interactions can generate the production of hydrogen peroxide (H(2)O(2)) in cells, the implications of which are becoming appreciated. Fluctuations in H(2)O(2) levels can affect the intracellular activity of key signaling components including protein kinases and protein phosphatases. Rhee et al. discuss recent findings on the role of H(2)O(2) in signal transduction. Specifically, H(2)O(2) appears to oxidize active site cysteines in phosphatases, thereby inactivating them. H(2)O(2) also can activate protein kinases; however, although the mechanism of activation for some kinases appears to be similar to that of phosphatase inactivation (cysteine oxidation), it is unclear how H(2)O(2) promotes increased activation of other kinases. Thus, the higher levels of intracellular phosphoproteins observed in cells most likely occur because of the concomitant inhibition of protein phosphatases and activation of protein kinases.

Animals↗

PubMed2000

A method for determining the reference effective flow areas for mechanical heart valve prostheses: in vitro validation studies.

BACKGROUND: The anatomic opening area (AOA) is usually reported as the primary index of mechanical heart valve function. Because flow contracts immediately distal to an orifice as a result of the vena contracta effect, AOA may not be a good measure of true effective flow area. METHODS AND RESULTS: Laser flow imaging was used to visualize the contraction in the jet flow stream as it passed through bileaflet mechanical valves under steady and pulsatile conditions. Such visualization allowed clear measurement of the individual vena contracta areas (VCAs) of the 3 valve orifices. VCAs for side orifices were larger (94+/-2% of AOA) than those through the central orifice (34+/-8%). Formation of large radial vortices around the leaflet tips constricted the central orifice flow stream and appeared to be the main reason for smaller central VCA. Total VCA remained constant until approximately 0.5 orifice diameters ( approximately 1.0 cm) downstream, beyond which cross-sectional area increased as a result of entrainment of receiving chamber flow. Total VCA was larger for steady flow (89.6+/-2.7% of AOA) than for pulsatile flow (76.3+/-5.0% of AOA). CONCLUSIONS: This study further clarifies flow dynamics through bileaflet mechanical valves and provides previously unavailable reference information on VCAs for these valves. Such information should aid clinicians in explaining Doppler-derived and catheter-measured pressure discrepancies, validating clinical techniques for quantifying effective flow areas, and optimizing valve size for implantation. The method should also be useful for comparative studies of different valve designs.

Echocardiography↗

PubMed2000

Mammalian thioredoxin reductase: oxidation of the C-terminal cysteine/selenocysteine active site forms a thioselenide, and replacement of selenium with sulfur markedly reduces catalytic activity.

Mammalian cytosolic thioredoxin reductase (TrxR) has a redox center, consisting of Cys(59)/Cys(64) adjacent to the flavin ring of FAD and another center consisting of Cys(497)/selenocysteine (SeCys)(498) near the C terminus. We now show that the C-terminal Cys(497)-SH/SeCys(498)-Se(-) of NADPH-reduced enzyme, after anaerobic dialysis, was converted to a thioselenide on incubation with excess oxidized Trx (TrxS(2)) or H(2)O(2). The Cys(59)-SH/Cys(64)-SH pair also was oxidized to a disulfide. At lower concentrations of TrxS(2), the Cys(59)-SH/Cys(64)-SH center was still converted to a disulfide, presumably by reduction of the thioselenide to Cys(497)-SH/SeCys(498)-Se(-). Specific alkylation of SeCys(498) completely blocked the TrxS(2)-induced oxidation of Cys(59)-SH/Cys(64)-SH, and the alkylated enzyme had negligible NADPH-disulfide oxidoreductase activity. The effect of replacing SeCys(498) with Cys was determined by using a mutant form of human placental TrxR1 expressed in Escherichia coli. The NADPH-disulfide oxidoreductase activity of the purified Cys(497)/Cys(498) mutant enzyme was 6% or 11% of that of wild-type rat liver TrxR1 with 5, 5'-dithiobis(2-nitrobenzoic acid) or TrxS(2), respectively, as substrate. Disulfide formation induced by excess TrxS(2) in the mutant form was 12% of that of the wild type. Thus, SeCys has a critical redox function during the catalytic cycle, which is performed poorly by Cys.

Animals↗

PubMed2000

Histone acetylation and hSWI/SNF remodeling act in concert to stimulate V(D)J cleavage of nucleosomal DNA.

The ordered assembly of immunoglobulin and TCR genes by V(D)J recombination depends on the regulated accessibility of individual loci. We show here that the histone tails and intrinsic nucleosome structure pose significant impediments to V(D)J cleavage. However, alterations to nucleosome structure via histone acetylation or by stable hSWI/SNF-dependent remodeling greatly increase the accessibility of nucleosomal DNA to V(D)J cleavage. Moreover, acetylation and hSWI/SNF remodeling can act in concert on an individual nucleosome to achieve levels of V(D)J cleavage approaching those observed on naked DNA. These results are consistent with a model in which regulated recruitment of chromatin modifying activities is involved in mediating the lineage and stage-specific control of V(D)J recombination.

Acetylation↗

PubMed1999

Construction of a detailed physical and transcript map of the FTDP-17 candidate region on chromosome 17q21.

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is an autosomal dominant condition clinically characterized by behavioral, cognitive, and motor disturbances. Until now, at least 13 different FTDP-17 families that show linkage to chromosome 17q21 have been described. To characterize the FTDP-17 candidate region, flanked by the markers D17S1789 and D17S1804, we constructed a physical map in P1 and PAC clones. A detailed transcript map was generated by positioning known genes and EST clusters to the physical map. In total, we investigated 150 STSs mapped to this region. In addition, novel transcripts were isolated by exon-trapping. We were able to localize 19 known genes and a number of ESTs to this chromosomal region. Furthermore, seven novel genes were identified for which we isolated the full-length sequence.

Base Sequence↗

PubMed1999

Clomipramine vs desipramine crossover trial in body dysmorphic disorder: selective efficacy of a serotonin reuptake inhibitor in imagined ugliness.

BACKGROUND: Body dysmorphic disorder (preoccupation with an imagined or slight defect in appearance) is a common and disabling disorder associated with high rates of delusional symptoms and suicide attempts. Although preliminary studies suggest that serotonin reuptake inhibitors may be effective for body dysmorphic disorder, to date no controlled treatment studies have been published. METHODS: Forty patients were enrolled and 29 were randomized into a 16-week, double-blind, crossover-design study of clomipramine, a potent serotonin reuptake inhibitor, and active control desipramine, a selective norepinephrine reuptake inhibitor. Outcome measures included specific ratings of body dysmorphic disorder severity, delusionality, and functional impairment. RESULTS: Clomipramine was superior to desipramine in the acute treatment of body dysmorphic disorder symptoms as measured by assessment of patients' obsessive preoccupation with perceived body defects, repetitive behaviors in response to this preoccupation, and global ratings of symptom severity. Treatment efficacy was independent of the presence or severity of comorbid diagnoses of obsessive-compulsive disorder, depression, or social phobia. Likewise, clomipramine was equally effective regardless of whether the patients had insight or held their dysmorphic misperception with delusional intensity. Clomipramine was also superior to desipramine in improving functional disability. CONCLUSIONS: Clomipramine is more effective than desipramine in the treatment of body dysmorphic disorder and is effective even among those patients who are delusional.

Adrenergic Uptake Inhibitors↗

PubMed1999

Real-time 3-dimensional volumetric ultrasound imaging of the vena contracta for stenotic valves with the use of echocardiographic contrast imaging: in vitro pulsatile flow studies.

The purpose of our study was to investigate the utility of real-time 3-dimensional volumetric ultrasound coupled with echo contrast imaging to visualize and quantify effective flow areas for stenotic valves in vitro. Real-time 3-dimensional ultrasound imaging has recently emerged as a promising method for increasing the quantitative accuracy of echocardiography. Since the technique currently does not process Doppler information, its use for quantifying flow has not been studied. However, the use of contrast agents to visualize cardiac flows with the use of echocardiography should allow determination of mass-dependent flow parameters such as effective flow area (vena contracta area) for stenotic lesions. We used real-time 3-dimensional imaging in an in vitro stenotic valve model (areas 0.785 to 1.767 cm2) under pulsatile flow conditions (60 bpm; 40 to 80 mL/beat). An echo contrast agent was used to visualize the distal jet. Real-time 3-dimensional imaging provides simultaneous views of long-axis and short-axis (C-scan) image planes of the jet. The vena contracta was identified and measured by placing the C-scan line immediately distal to the orifice and measuring the cross-sectional flow area. System gain and postprocessing curve shape affected 3-dimensional areas; minimal gain and a custom curve produced best agreement to actual vena contracta areas measured with a previously validated laser method (y = 0.939x + 0.089; r = 0.98; standard error of estimate = 0.158 cm2). We conclude that real-time 3-dimensional ultrasound imaging coupled with a contrast agent can be used as an accurate yet simple clinical means of measuring effective flow areas for stenotic valves.

Albumins↗