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Biomedical subjects

S Lee

Publications and source records attributed to S Lee.

At least 19 recordsLinked to original sources

Plant size, not age, regulates growth and gas exchange in grafted Scots pine trees.

We studied the effect of scion donor-tree age on the physiology and growth of 6- to 7-year-old grafted Scots pine (Pinus sylvestris L.) trees (4 and 5 years after grafting). Physiological measurements included photosynthethetic rate, stomatal conductance, transpiration, whole plant hydraulic conductance, needle nitrogen concentration and carbon isotope composition. Growth measurements included total and component biomasses, relative growth rates and growth efficiency. Scion donor trees ranged in age from 36 to 269 years at the time of grafting. Hydraulic conductance was measured gravimetrically, applying the Ohm's law analogy, and directly, with a high-pressure flow meter. We found no effect of scion donor-tree age on any of the variables measured. There was, however, great variation within scion donor-tree age groups, which was related to the size of the grafted trees. Differences in size may have been caused by variable initial grafting success, but there was no indication that grafting success and age were related. At the stem level, hydraulic conductance scaled with total leaf area so that total conductance per unit leaf area did not vary with crown size. However, leaf specific hydraulic conductance (gravimetric), transpiration, photosynthesis and stomatal conductance declined with increasing total tree leaf area and needle width. We hypothesize that needle width is inversely related to mesophyll conductance. We conclude that canopy and needle size and not scion donor-tree age determined gas exchange in our grafted trees.

Pinus sylvestris↗

Phosphorus balance and mineral metabolism with 3 h daily hemodialysis.

Poor control of mineral metabolism is independently associated with mortality in patients receiving hemodialysis. We analyzed data from a 12-month, prospective, non-randomized, controlled study of daily hemodialysis (DHD) (six sessions/week 3 h each) (n=26) vs conventional hemodialysis (CHD) (three sessions/week 4 h each) (n=51) for achievement of mineral metabolism goals and we performed a substudy of weekly dialytic phosphorus removal in DHD vs CHD. Phosphorus control was superior in the DHD group (% change from baseline to end-of-study -27+/-30% vs +7%+/-35% in the CHD group, P=0.0001). Percentage of patients using phosphate binders decreased from 77 to 40% among subjects on DHD, whereas these parameters did not change (76 vs 77%) in the CHD group (P=0.03 by Breslow-Day test for homogeneity of the odds ratios). Weekly mean phosphorus removal was higher in the DHD group (2452+/-720 mg/week vs 1572+/-366 mg/week, P=0.04). Mean normalized protein catabolic rate increased (0.90+/-0.43-1.22+/-0.26 g/kg/day, P=0.0013). DHD was also associated with an increase in the percent of subjects achieving three or more mineral metabolism goals (for phosphorus, calcium x phosphorus and parathyroid hormone) (15 vs 46%, P=0.046). In conclusion, DHD improves phosphorus control by increasing dialytic phosphorus removal while maintaining nutritional status and reducing the use of phosphate binders. The net effect allows for improved achievement of mineral metabolism goals.

Adult↗

DA-9601 inhibits activation of the human mast cell line HMC-1 through inhibition of NF-kappaB.

Mast cell-mediated allergic inflammation is involved in many diseases such as asthma, sinusitis, and rheumatoid arthritis. Mast cells induce synthesis and production of pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 with immune regulatory properties. The formulated ethanol extract of Artemisia asiatica Nakai (DA-9601) has been reported to have antioxidative and anti-inflammatory activities. In this report, we investigated the effect of DA-9601 on the expression of pro-inflammatory cytokines by the activated human mast cell line HMC-1 and studied its possible mechanisms of action. DA-9601 dose-dependently decreased the gene expression and production of TNF-alpha, IL-1beta, and IL-6 on phorbol 12-myristate 13-acetate (PMA)- and calcium ionophore A23187-stimulated HMC-1 cells. In addition, DA-9601 attenuated PMA- and A23187-induced activation of NF-kappaB as indicated by inhibition of degradation of IkappaBalpha, nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay. Our in vitro studies provide evidence that DA-9601 might contribute to the treatment of mast cell-derived allergic inflammatory diseases.

Artemisia↗

Genetic modification of the manganese superoxide dismutase/glutathione peroxidase 1 pathway influences intracellular ROS generation in quiescent, but not contracting, skeletal muscle cells.

Increased amounts of reactive oxygen species (ROS) are generated by skeletal muscle during contractile activity, but their intracellular source is unclear. The oxidation of 2',7'-dichlorodihydrofluorescein (DCFH) was examined as an intracellular probe for reactive oxygen species in skeletal muscle myotubes derived from muscles of wild-type mice and mice that were heterozygous knockout for manganese superoxide dismutase (Sod2(+/-)), homozygous knockout for glutathione peroxidase 1 (GPx1(-/-)), or MnSOD transgenic overexpressors (Sod2-Tg). Myoblasts were stimulated to fuse and loaded with DCFH 5-7 days later. Intracellular DCF epifluorescence was measured and myotubes were electrically stimulated to contract for 15 min. Quiescent myotubes with decreased MnSOD or GPx1 showed a significant increase in the rate of DCFH oxidation whereas those with increased MnSOD did not differ from wild type. Following contractions, myotubes from all groups showed an equivalent increase in DCF fluorescence. Thus the oxidation of DCFH in quiescent skeletal muscle myotubes is influenced by the content of enzymes that regulate mitochondrial superoxide and hydrogen peroxide content. In contrast, the increase in DCFH oxidation following contractions was unaffected by reduced or enhanced MnSOD or absent GPx1, indicating that reactive oxygen species produced by contractions were predominantly generated by nonmitochondrial sources.

Animals↗

Attenuated pain responses in mice lacking Ca(V)3.2 T-type channels.

Although T-type Ca(2+) channels are implicated in nociception, the function of specific subtypes has not been well defined. Here, we compared pain susceptibility in mice lacking Ca(V)3.2 subtype of T-type Ca(2+) channels (Ca(V)3.2(-/-)) with wild-type littermates in various behavioral models of pain to explore the roles of Ca(V)3.2 in the processing of noxious stimuli in vivo. In acute mechanical, thermal and chemical pain tests, Ca(V)3.2(-/-) mice showed decreased pain responses compared to wild-type mice. Ca(V)3.2(-/-) mice also displayed attenuated pain responses to tonic noxious stimuli such as intraperitoneal injections of irritant agents and intradermal injections of formalin. In spinal nerve ligation-induced neuropathic pain, however, behavioral responses of Ca(V)3.2(-/-) mice were not different from those of wild-type mice. The present study reveals that the Ca(V)3.2 subtype of T-type Ca(2+) channels are important in the peripheral processing of noxious signals, regardless of modality, duration or affected tissue type.

Animals↗

Naphthalenemethyl ester derivative of dihydroxyhydrocinnamic acid, a component of cinnamon, increases glucose disposal by enhancing translocation of glucose transporter 4.

AIMS/HYPOTHESIS: Cinnamon extracts have anti-diabetic effects. Phenolic acids, including hydrocinnamic acids, were identified as major components of cinnamon extracts. Against this background we sought to develop a new anti-diabetic compound using derivatives of hydroxycinnamic acids purified from cinnamon. METHODS: We purified hydroxycinnamic acids from cinnamon, synthesised a series of derivatives, and screened them for glucose transport activity in vitro. We then selected the compound with the highest glucose transport activity in epididymal adipocytes isolated from male Sprague-Dawley rats in vitro, tested it for glucose-lowering activity in vivo, and studied the mechanisms involved. RESULTS: A naphthalenemethyl ester of 3,4-dihydroxyhydrocinnamic acid (DHH105) showed the highest glucose transport activity in vitro. Treatment of streptozotocin-induced diabetic C57BL/6 mice and spontaneously diabetic ob/ob mice with DHH105 decreased blood glucose levels to near normoglycaemia. Further studies revealed that DHH105 increased the maximum speed of glucose transport and the translocation of glucose transporter 4 (GLUT4, now known as solute carrier family 2 [facilitated glucose transporter], member 4 [SLC2A4]) in adipocytes, resulting in increased glucose uptake. In addition, DHH105 enhanced phosphorylation of the insulin receptor-beta subunit and insulin receptor substrate-1 in adipocytes, both in vitro and in vivo. This resulted in the activation of phosphatidylinositol 3-kinase and Akt/protein kinase B, contributing to the translocation of GLUT4 to the plasma membrane. CONCLUSIONS/INTERPRETATION: We conclude that DHH105 lowers blood glucose levels through the enhancement of glucose transport, mediated by an increase in insulin-receptor signalling. DHH105 may be a valuable candidate for a new anti-diabetic drug.

Adipocytes↗

The new definition of metabolic syndrome by the international diabetes federation is less likely to identify metabolically abnormal but non-obese individuals than the definition by the revised national cholesterol education program: the Korea NHANES study.

OBJECTIVE: The new definitions for metabolic syndrome (MS) proposed by the IDF and revised NCEP have caused some confusion because patients have emerged that have satisfied the revised NCEP but not the IDF criteria. We performed this study to compare the prevalence of these criteria and to investigate the characteristics of discrepant cases. RESEARCH DESIGN AND METHODS: A total of 7962 individuals aged >or= 20 years (3597 men; 4365 women) who participated in the 1998 Korean NHANES were included. We assessed the agreement between the revised NCEP and IDF criteria and investigated the characteristics of cases satisfying the revised NCEP criteria but not the IDF criteria. RESULTS: The prevalence of MS by the revised NCEP (25.7% of men and 31.9% of women) was higher than that according to the IDF (14.2% of men and 26.6% of women). The IDF criteria failed to identify 44.9% of men and 16.6% of women identified as having MS according to the revised NCEP criteria. The discrepant group showed more adverse metabolic profiles and unfavorable lifestyles despite lower waist circumference as compared with those having MS by both the IDF and revised NCEP criteria. The prevalence of discrepant cases was higher among the elderly. CONCLUSIONS: The IDF criteria were inferior to the revised NCEP criteria in identifying the metabolically abnormal but nonobese groups known to be predisposed to type 2 diabetes and cardiovascular disease. Further research regarding the appropriateness of central obesity as an obligatory criterion proposed by the IDF seems to be warranted.

Adult↗

Anisotropic drude response and the effect of anisotropic C substitution in.

The in-plane and the out-of-plane optical spectra of small single crystals of Mg(B1-xCx)2 were directly determined by a microscope spectroscopy technique. Contrary to previous reports, the estimated plasma frequencies for both directions are quite consistent with the band calculation. A multi-Drude picture corresponding to a multiband system is necessary to explain the whole spectral profile. The spectral changes with the carbon substitution indicate a decrease of carrier concentration as well as an increase of scattering rate, particularly, in the sigma bands.

Journal Article↗

Respiratory system of Gluconacetobacter diazotrophicus PAL5. Evidence for a cyanide-sensitive cytochrome bb and cyanide-resistant cytochrome ba quinol oxidases.

In highly aerobic environments, Gluconacetobacter diazotrophicus uses a respiratory protection mechanism to preserve nitrogenase activity from deleterious oxygen. Here, the respiratory system was examined in order to ascertain the nature of the respiratory components, mainly of the cyanide sensitive and resistant pathways. The membranes of G. diazotrophicus contain Q(10), Q(9) and PQQ in a 13:1:6.6 molar ratios. UV(360 nm) photoinactivation indicated that ubiquinone is the electron acceptor for the dehydrogenases of the outer and inner faces of the membrane. Strong inhibition by rotenone and capsaicin and resistance to flavone indicated that NADH-quinone oxidoreductase is a NDH-1 type enzyme. KCN-titration revealed the presence of at least two terminal oxidases that were highly sensitive and resistant to the inhibitor. Tetrachorohydroquinol was preferentially oxidized by the KCN-sensitive oxidase. Neither the quinoprotein alcohol dehydrogenase nor its associated cytochromes c were instrumental components of the cyanide resistant pathway. CO-difference spectrum and photodissociation of heme-CO compounds suggested the presence of cytochromes b-CO and a(1)-CO adducts. Air-oxidation of cytochrome b (432 nm) was arrested by concentrations of KCN lower than 25 microM while cytochrome a(1) (442 nm) was not affected. A KCN-sensitive (I(50)=5 microM) cytochrome bb and a KCN-resistant (I(50)=450 microM) cytochrome ba quinol oxidases were separated by ion exchange chromatography.

Bacterial Proteins↗

Perforin polymorphism A91V and susceptibility to B-precursor childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group.

Perforin plays a key role in the cytotoxicity of natural killer and cytotoxic T cells. Genetic mutations in the perforin gene (PRF1) give rise to approximately 30% cases of familial hemophagocytic lymphohistiocytosis. A frequent polymorphism, A91V (C to T transition at position 272), may impair processing of perforin protein to the active form, and has been suggested to increase susceptibility to childhood acute lymphoblastic leukemia (ALL). To investigate the role of A91V in ALL, we genotyped 2272 children with de novo ALL registered on the Pediatric Oncology Group ALL Classification study P9900 and 655 normal controls. Allele frequencies in the controls showed a very low frequency of the variant allele in blacks, 0.7% compared to 4% in white controls. In light of this, analysis was restricted to a comparison of white cases and controls only. Overall genotype frequencies were similar in white ALL cases and normal white controls (P=0.58), indicating that in contrast to the previous report, A91V polymorphism is not associated with increased risk of childhood ALL. PRF1 A91V frequency was significantly increased in children with BCR-ABL positive ALL (24 vs 8.5%; P=0.0048); however, this observation includes a relatively small number of cases and needs further exploration.

Base Sequence↗

Minimization of immunosuppressive therapy after islet transplantation: combined action of heme oxygenase-1 and PEGylation to islet.

We previously established a type of PEGylated islets to attenuate cellular immune reactions by immobilizing polyethylene glycol (PEG) molecules on islet surfaces, thereby synergistically reducing the dose of immunosuppressant cyclosporine A (CsA; 3 mg/kg/day) to protect transplanted islets. However, higher doses of immunosuppressants should be administered after islet transplantation due to nonspecific inflammation. This study documents that PEGylated islets can be cooperatively protected by the systemic overexpression of heme oxygenase-1 (HO-1), which has a potent cytoprotective function in preventing nonspecific inflammation during an early stage following islet transplantation. Under this scheme, the viability of PEGylated islets was improved; that is, PEG molecules could block cellular immunity and HO-1 could exert its cytoprotective property against inflammation. Interestingly, when employed with a low dose of CsA (1 mg/kg/day), a cooperative action of PEG molecules and HO-1 in immune reactions could result in the complete survival of transplanted islets for 100 days without islet function impairment. However, unmodified islets (control) were completely rejected within 2 weeks despite cotreatment with HO-1 expression and CsA. These results demonstrated that the combinatorial protocol of initial induction of HO-1 expression, followed by the daily administration of a low dose CsA after transplantation of PEGylated islets can be employed as a successful cell therapy in clinical islet transplantation.

Animals↗

Arginine-16 beta2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol.

BACKGROUND: The homozygous presence of the arginine-16 variant of the beta(2) adrenoceptor gene ADRB2 reverses the benefits from the regular use of short acting beta(2) agonists in asthmatic adults compared with the homozygous glycine-16 genotype. We studied the effect of this polymorphic variation on asthma exacerbations in children and young adults and its relation to long acting beta(2) agonists. METHODS: A cross-sectional survey was undertaken using electronic records, direct interviews, and genotype determination of position 16 and 27 of the ADRB2 gene in DNA from mouthwash samples of 546 children and young asthmatics attending paediatric and young adult asthma clinics in Tayside, Scotland during 2004-5. The primary outcome measure was asthma exacerbations over the previous 6 months. RESULTS: There was an increased hazard of asthma exacerbations across all treatment steps of the British Thoracic Society (BTS) asthma guidelines when the homozygous genotypes Arg/Arg and Gly/Gly were compared (OR 2.05, 95% CI 1.19 to 3.53, p = 0.010), particularly in patients treated with salmeterol (OR 3.40, 95% CI 1.19 to 9.40, p = 0.022). The Glu27Gln polymorphism had no significant effect on asthma exacerbations in any treatment group. CONCLUSIONS: The arginine-16 genotype of ADRB2 predisposes to exacerbations in asthmatic children and young adults, particularly in those exposed to regular salmeterol. This may be explained by genotype selective salmeterol induced downregulation and impaired receptor coupling, and associated subsensitivity of the response.

Adolescent↗

Alcohol use among entrants to a Hong Kong University.

AIM: This study of first year entrants to one of the major universities in Hong Kong describes the pattern of their alcohol consumption, their binge drinking, alcohol abuse, and dependence. METHODS: A retrospective cross-sectional study was conducted. A representative sample of year 1 students 2630/2968 (89%) newly admitted to the Chinese University of Hong Kong in 2003 were recruited to participate in a structured self-administered questionnaire. RESULTS: First year university students in Hong Kong have low rates of ever drinking alcohol (62%), and the rates of binge drinking and alcohol-related problems were 7 and 0.8%, respectively. The pattern of binge drinking is more common than weekly drinking (2.3%). Binge drinkers are more likely to have experienced alcohol-related interpersonal problems or (95% CI) = 6.5 (1.7-24.5). Males were more likely to drink, to binge drink, and to drink frequently. CONCLUSIONS: In contrast with students in the west, the majority of first year university students in Hong Kong are not binge or regular drinkers. However, there is a subgroup who smoke, drink more, and use alcohol as a means of coping with stress. This group may be particularly in need of a brief intervention, such as providing counseling and referral services.

Adolescent↗

Vascular endothelial growth factor (VEGF) is associated with reduced severity of acute graft-versus-host disease and nonrelapse mortality after allogeneic stem cell transplantation.

This study investigated whether or not there is a correlation between the changes in the serum levels of vascular endothelial growth factor (VEGF) and the outcome of allogeneic stem cell transplantation (allo-SCT). Eighty-five patients undergoing allo-SCT were prospectively studied. The serum VEGF levels were measured on days 0, +7 and +14 after transplantation. The VEGF levels decreased significantly on day +7 and recovered on day +14. The highest levels from day +7 through day +14 were categorized by cluster analysis, which were then correlated with the nonrelapse mortality (NRM). There was a significant correlation between a low VEGF level and the occurrence of severe acute graft-versus-host disease (GVHD) including grade III-IV (P=0.029). The 1-year probability of NRM in patients with a low VEGF level was 22.5% compared with 3.5% for those with a high VEGF level (P=0.024). Multivariate analysis revealed clinically defined infections (P=0.011), advanced disease (P=0.014) and a low VEGF cluster (P=0.05) to be significantly associated with the occurrence of NRM in the cohort. In conclusion, low VEGF levels after allo-SCT are associated with NRM with an exacerbated severity of acute GVHD. VEGF monitoring after a transplant might identify those patients at risk of severe transplant-related mortality.

Acute Disease↗

Exogenous cytokinin treatment maintains cyclin homeostasis in rice seedlings that show changes of cyclin expression when the photoperiod is rapidly changed.

Cyclin is a fundamental regulator of the plant cell cycle. Five different types of cyclin genes (the A-, B-, C-, D-, and H-types) have been reported in Oryza sativa. However, except for Os;cycA1;1, Os;cycB2;1, and Os;cycB2;2, the mechanisms of expression of these cyclin genes have not yet been studied. The interactions of cyclins with cytokinin, an important trigger for cell cycle regulation, have also not been well studied. Here we used semi-quantitative RT-PCR in rice seedlings to analyze the effect of cytokinin on photomorphogenesis and the expression of six cyclin genes. Fifteen-day-old seedlings were grown in a 16/8 h light/dark cycle and then transferred to either constant light or constant dark. The expression of all the cyclin genes tested, except the C-type, decreased after 1 hour in the dark, but did not change after transfer to the light or when kinetin was added to the medium. Similarly, seedlings grown in the dark had decreased expression of the cyclin genes, except Os;cycB2;2, after transfer to the light, a decrease that was prevented by kinetin treatment. Thus, exogenous cytokinin plays an important role in maintaining homeostasis of cyclin gene expression following rapid changes of photoperiod.

Cyclins↗

PEGylated glucagon-like peptide-1 displays preserved effects on insulin release in isolated pancreatic islets and improved biological activity in db/db mice.

AIMS/HYPOTHESIS: The rapid degradation and clearance of glucagon-like peptide-1 (GLP-1) by the enzymes dipeptidyl peptidase-IV and neutral endopeptidase 24.11 are the main impediments to the development of GLP-1 as a potential glucose-lowering agent. In this study, new enzyme-resistant polyethylene glycol (PEG)-conjugated GLP-1 analogues were designed and examined for metabolic stability and biological potency. MATERIALS AND METHODS: Two mono-PEGylated GLP-1 analogues, N-terminally modified N-PEG/GLP-1 and Lys-modified Lys-PEG/GLP-1, were prepared. Stability was tested in plasma and tissue extracts. In vitro insulin release studies were performed using isolated rat pancreatic islets, while in vivo glycaemic responses were measured in db/db mice. RESULTS: The half-life of Lys-PEG/GLP-1 was 40-, 10- and 28-fold longer than that of GLP-1 in plasma, liver and kidney homogenates, respectively. Lys-PEG/GLP-1 stimulated insulin secretion in the islets in a dose- and glucose-dependent manner, and was as potent as GLP-1. In contrast, N-PEG/GLP-1 showed extended metabolic stability but had significantly lower biological activity. The administration of Lys-PEG/GLP-1 (9 nmol/kg i.p.) to non-fasted db/db mice stabilised glycaemia (p<0.001), whereas GLP-1 (9 nmol/kg) only caused small changes in glucose level. During OGTT in fasted db/db mice, Lys-PEG/GLP-1 administered at 1, 3 and 9 nmol/kg (i.p.) reduced the glucose AUC(0-3h) by 48.7+/-9.4, 55.0+/-2.9 and 63.4+/-2.5%, respectively, compared with placebo (p<0.01), whereas GLP-1 (9 nmol/kg) lowered the glucose level by 39.5+/-12.9% (p<0.01). CONCLUSIONS/INTERPRETATION: This study demonstrates that site-specific PEGylated GLP-1 analogues are resistant to degradation. The enhanced biological potencies of these analogues highlight their potential as new, GLP-1-like glucose-lowering agents.

Animals↗

Evaluation of a modified antimycobacterial susceptibility test using Middlebrook 7H10 agar containing 2,3-diphenyl-5-thienyl-(2)-tetrazolium chloride.

A rapid and accurate antimycobacterial susceptibility test is essential for effective treatment of tuberculosis. The aim of this study was to evaluate a modified method applying 2,3-diphenyl-5-thienyl-(2)-tetrazolium chloride (STC) to the Clinical and Laboratory Standards Institute (CLSI) guideline for susceptibility testing of Mycobacterium tuberculosis. A total of 132 clinical isolates of M. tuberculosis, forty-eight isolates showing resistance to one or more of the first-line antituberculosis drugs, and eighty-four fully susceptible isolates were collected from hospitals of a nationwide distribution from June to September 2004. The modified procedure was conducted basically according to the agar-proportion method described in the CLSI Guideline both with STC 50 mug/mL. The amount of growth in each well was recorded and graded at 2nd and 3rd weeks after inoculation. After 3 weeks of incubation, the diagnostic sensitivity and specificity for the detection of drug-resistant strains of STC-containing agar proportion methods were 100%, except ethambutol-low level resistance, of which the diagnostic sensitivity was 93.4%. After two weeks of incubation in STC-containing agar proportion methods, one hundred of the 107 strain-drug combinations have shown drug resistance, indicating the sensitivity of 93.5%. Especially, all 41 isoniazid-resistant strains and 19 of 21 rifampin-resistant strains (90.5%) could be detected after two weeks of incubation. A modification of the agar proportion method using STC resulted in a reliable and more easily interpretable data, and detected most of resistant strains a week earlier than conventional method.

Agar↗