Effects of pesticides and their hydrolysates on catalase activity in soil.
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Biomedical subjects
Publications and source records attributed to S Cheng.
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Myelin-associated glycoprotein (MAG) has been implicated in inhibition of nerve regeneration in the CNS. This results from interactions between MAG and the Nogo receptor and gangliosides on the apposing axon, which generates intracellular inhibitory signals in the neuron. However, because myelin-axon signaling is bidirectional, we undertook an analysis of potential MAG-activated signaling in oligodendrocytes (OLs). In this study, we show that antibody cross-linking of MAG on the surface of OLs (to mimic axonal binding) leads to the redistribution of MAG into detergent (TX-100)-insoluble complexes, hyperphosphorylation of Fyn, dephosphorylation of serine and threonine residues in specific proteins, including lactate dehydrogenase and the beta subunit of the trimeric G-protein-complex, and cleavage of alpha-fodrin followed by a transient depolymerization of actin. We propose that these changes are part of a signaling cascade in OLs associated with MAG function as a mediator of axon-glial communication which might have implications for the mutual regulation of the formation and stability of axons and myelin.
The effects of the reactive oxygen species (ROS) superoxide anion (O2*-) and hydroxyl radical (*OH) on the surface tension lowering properties of bovine lipid extract surfactant (BLES) were compared to the effects of calf serum protein (CSP) in a captive bubble surfactometer (CBS). O2*- was generated from xanthine/xanthine oxidase (X/XO), and *OH was generated by the Fenton reaction. ROS were demonstrated by electron spin resonance (ESR) using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as the spin trap. Lipid peroxidation was measured using the thiobarbituric acid method. *OH had broad inhibitory effects on surface tension parameters, including adsorption, minimum surface tension, percentage film area change and film compressibility. O2*- showed inhibitory effects on adsorption, film area change and film compressibility but had no significant effect on minimum surface tension. Both O2*- and *OH treatment were associated with a large 'squeezeout' plateau around 20-25 mN/m in the surface tension-area relation, indicating poor film organization during the compression phase. At the concentrations used, ROS were associated with lipid peroxidation of BLES, which also demonstrated radical scavenging properties. Calf serum protein produced inhibitory effects on adsorption, minimum surface tension and percentage film area change that were quantitatively similar to those produced by *OH. The effects on film compression were significantly greater and qualitatively different from those seen with either O2*- or *OH. We conclude that the inhibition of BLES surface activity by ROS and inhibitory proteins can be distinguished in the captive bubble surfactometer and, particularly, by changes in the film compressibility modulus.
Candida albicans is the most common fungal opportunistic pathogen of humans and causes mucocutaneous, bloodstream and deep organ infections. Screening for C. albicans genes that are preferentially expressed within infected hosts represents a strategy to identify novel virulence factors and define global expression patterns relevant to pathogenesis. Until recently, C. albicans has not been amenable to screening using existing technologies. This has begun to change with the development of new molecular genetic tools and the sequencing of the C. albicans genome. In this paper, we review studies using recently developed techniques to identify genes expressed by C. albicans during infections, as well as work from our laboratory using a human antibody-based strategy. Along with others, we have shown that selected in vivo expressed genes encode known and previously unrecognized candidal virulence factors. Future studies in this area will identify additional novel virulence factors, as well as advance our understanding of pathogenesis.
BACKGROUND: Increased oxidative stress is thought to play a role in the pathogenesis of the atherothrombotic process. Paraoxonases (PONs) are closely related antioxidant enzymes encoded by clustered genes on chromosome 7q. We evaluated three PON polymorphisms (PON1 Leu55Met and Gln192Arg; PON2 Ser311Cys) as possible risk factors for coronary atherosclerotic disease (CAD) and/or its main thrombotic complication, myocardial infarction (MI). MATERIALS AND METHODS: We studied 890 subjects with angiographic documentation of coronary vessels (272=CAD-free; 618=CAD). In the CAD group, 341 subjects had a previous MI. RESULTS: Frequencies of various genotypes were not significantly different between CAD-free subjects and the entire CAD population. In the latter group, there were more carriers of the PON2 311Cys variation among those who had suffered a MI than among those who had not (P<0.01 by chi2). The adjusted OR for MI among PON2 311Cys carriers was 1.5 (95%CI, 1.03-2.19). A gene-environmental interaction was found between PON2 Ser311Cys and smoking. Smoking by itself was associated with an increased MI risk. Among smokers, however, the MI risk was related to PON2 genotype: Cys/Cys homozygotes (OR=5.3; 95%CI, 1.7-16.4) and Ser/Cys heterozygotes (OR=2.1; 95%CI, 1.3-3.6) were at greater risk than Ser/Ser subjects (OR=1.2; 95%CI, 0.8-1.8). The PON2 polymorphism did not influence the MI risk among nonsmokers. CONCLUSIONS: In CAD subjects, a proportion of the risk of MI may be influenced by the interaction between smoking and a polymorphism in the antioxidant enzyme PON2.
AIMS: To ascertain whether there is an increased risk of cancers of the lung and lymphohaematopoietic tissue in workers employed in the New Zealand meat processing industry, and to identify exposures associated with any increased risks. METHODS: A cohort of 6647 individuals assembled from personnel records from three plants was followed from 1988 until 2000. The observed number of deaths and cancer registrations was compared with expected numbers using five year age and gender specific rates for the New Zealand population. Subgroup analyses evaluated the effect of duration of exposure to selected agents, based on job titles and departments. RESULTS: Vital status was determined for 84% of the cohort, and 92% of the total possible person-years. Mortality from all causes and all cancers was increased, and there was a significant excess of lung cancer. There were significant trends of increasing risk of lung and lymphohaematopoietic cancer with increasing duration of exposure to biological material. CONCLUSIONS: Excess risks were observed for mortality from all causes, all cancers, and lung cancer. Although the increased risk of lung cancer may be partly due to confounding by smoking, it is unlikely to be entirely due to this cause. Furthermore, the dose-response relation observed for lung cancer suggests the effect is related to exposure to biological material contained in animal urine, faeces, and blood. Although numbers were small, the risk of lymphohaematopoietic cancer was also associated with increasing duration and level of exposure to biological material.
The purpose of this study was to compare low frequency ultrasonic guided wave measurements with established ultrasound and bone density measurements in terms of their ability to characterize the tibia in pubertal girls. Subjects were 12-14-year-old girls ( n=106) who were participating in a calcium and vitamin D intervention study. A prototype low frequency pulse transmission device consisting of a uniaxial scanning mechanism and low frequency transducers orientated perpendicularly to the limb was used to measure two ultrasound velocities in the tibia. The first velocity, V1, was that of the first arriving signal, similar to that measured by existing commercial tibial ultrasound devices. The second velocity, V2, was that of a slower wave propagating at 1,500-2,000 m/s, which has been shown elsewhere to be consistent with the lowest order antisymmetric guided mode in the bone. In addition, commercial ultrasound devices (Omnisense, Sunlight Ltd.; QUS-2, Quidel Corp.) were used to measure the speed of sound (SOS) in the tibia and the radius and attenuation (BUA) in the calcaneus. Cortical bone cross-sectional area (CSA), mineral density (BMD) and cortical thickness (cTh) of the tibia were measured using pQCT, site-matched to the ultrasound measurements. Both V1 and V2 correlated significantly with cortical BMD and with cTh and CSA. On the other hand, tibial SOS correlated with BMD, but not with cTh and CSA. These results indicate that the prototype device using guided waves captures aspects of tibial cortical bone geometry in addition to bone density, thereby potentially offering increased diagnostic information compared to existing tibial ultrasound devices.
Human autoimmune diseases are a class of complex immune system disorders characterized by loss of tolerance to self-antigens. HLA class II molecules play a central role in the initiation, propagation and prolongation of the disease process. HLA class II transgenic mice with mouse endogenous class II gene Ab knockout were used successfully in several mouse models for human autoimmune diseases, such as IDDM, SLE and EAE in our Lab. However, these mice carry the functional mouse Eb gene from the Abeta(0/0) construct and could express Ebeta/DRalpha(Ealpha) molecules and shape the T cell repertoire in these mice. Recently, we have obtained the new MHCII(Delta/Delta) mice that are devoid of all endogenous conventional mouse MHC class II genes. When these mice are mated with our HLA class II transgenic mice, only human class II genes are expressed. The DR and DQ molecules expressed in these mice shape the T cell repertoire and regulate the immune response. Therefore, this new class of HLA transgenic mice is the first to be completely "humanized" in their MHC class II genes and will be an invaluable mouse model for human MHC class II associated autoimmune diseases.
In this randomized, double-blind, placebo-controlled 12-month trial we evaluated effects of weight- bearing jumping exercise and oral alendronate, alone or in combination, on the mass and structure of bone, risk factors for falling (muscle strength and power, postural sway, and dynamic balance), and cardiorespiratory fitness in postmenopausal women. A total of 164 healthy, sedentary, early postmenopausal women were randomly assigned to one of four experimental groups: (1) 5 mg of alendronate daily plus progressive jumping exercise, (2) 5 mg alendronate, (3) placebo plus progressive jumping exercise, or (4) placebo. The primary endpoint was 12-month change in bone mass and geometry (measured with dual-energy X-ray absorptiometry and peripheral computed tomography at several axial and limb sites) and physical performance; the secondary endpoint was change in biochemical markers of bone turnover. The jumping exercise was conducted an average 1.6 +/- 0.9 (mean +/- SD) times a week. Alendronate daily was effective in increasing bone mass at the lumbar spine (alendronate vs placebo 3.5%; 95% CI, 2.2-4.9%) and femoral neck (1.3%; 95% CI, 0.2-2.4%) but did not affect other bone sites. Exercise alone had no effect on bone mass at the lumbar spine or femoral neck; it had neither an additive nor an interactive effect with alendronate at these bone sites. However, at the distal tibia the mean increase of 3.6% (0.3-7.1%) in the section modulus (that is, bone strength) and 3.7% (0.1-7.3%) increase in the ratio of cortical bone to total bone area were statistically significant in the exercise group compared to the nonexercise group, indicating exercise-induced thickening of the bone cortex. Bone turnover was reduced in alendronate groups only. Alendronate had no effect on physical performance while the jumping exercise improved leg extensor power, dynamic balance, and cardiorespiratory fitness. As conclusion Alendronate is effective in increasing bone mass at the lumbar spine and femoral neck, while exercise is effective in increasing the mechanical properties of bone at some of the most loaded bone sites, as well as improving the participants' muscular performance and dynamic balance. Together alendronate and exercise may effectively decrease the risk of osteoporotic fractures.
H2-M or HLA-DM are non-classical class II molecules encoded by the MHC and play an important role during antigen presentation. They catalyze exchange of CLIP (Class II-associated invariant chain peptide) or other low-affinity peptides bound to class II molecules for peptides capable of more efficient binding. The phenotype of mice lacking H2-M is determined by the allotype of the MHC class II molecules expressed. In general, H2-M deficiency does not affect the surface expression of mature class II molecules. The class II molecules in such cases predominantly contain CLIP in their peptide-binding groove. In some mice strains, H2-M deficiency results in defective CD4+ T-cell development accompanied by defective responses to conventional antigens and superantigens. Even though the HLA class II molecules show similar dependency for HLA-DM for presenting antigens in vitro, their interaction in vivo is not known. By using transgenic approach we show here that DQ8 and DR3 are expressed at normal levels in H2-M-deficient mice and the CD4+ T-cell development is unaltered. However, the ability of DQ8 molecules to present peptide antigens is compromised in a H2-M-deficient state. Presentation of exogenous bacterial superantigens by both DQ8 and DR3 is unaffected in H2-M-deficient mice. Unexpectedly, Staphylococcal Enterotoxin B-induced systemic IFN-gamma production was significantly higher in H2-M-deficient DQ8/DR3 transgenic mice and these mice were susceptible to SEB-induced toxic shock at doses that are non-lethal to H2-M-sufficient counterparts.
BACKGROUND: Although pollens are major allergens associated with allergic rhinoconjunctivitis and asthma, there is little information about the relative prevalence of these conditions in populations with different pollen exposures. OBJECTIVE: The purpose of this study was to investigate the relationship between pollen exposure and allergic symptoms among children in different countries. METHODS: An ecological analysis was conducted to see whether pollen exposure (pollen counts, and duration and severity of pollen seasons) is associated with symptoms of allergic rhinoconjunctivitis, asthma and atopic eczema in 28 centres within 11 countries (nine being in Europe). Data on the prevalence of symptoms in 13-14-year olds were based on the responses to the written questionnaires from the International Study of Asthma and Allergies in Childhood (ISAAC). The analysis was adjusted for gross national product and mean annual relative humidity. RESULTS: There was little relationship between pollen exposure and symptom prevalence, except for a significant inverse association between grass pollen counts and lifetime prevalence of the symptoms of allergic rhinitis (P=0.03). Almost all the regression coefficients were negative. The associations were even weaker and all non-significant when the analyses were conducted within countries, using a random intercept fixed slope model, but there was still no evidence of a positive association between pollen exposure and symptoms. CONCLUSION: There is a weak but consistent tendency for the prevalence of allergic symptoms to be inversely associated with pollen exposure. This finding accords with evidence from several countries, suggesting that the prevalence of hayfever and asthma tends to be lower in rural than in urban areas, and lowest among people living on farms. Exposure to allergenic pollen in early life does not appear to increase the risk of acquiring symptoms of respiratory allergy, and may even give some protection against them.
BACKGROUND: The rate of progression to cirrhosis varies among individuals chronically infected with the hepatitis C virus (HCV). Coagulation pathway activation in models of hepatic fibrosis suggests variation in coagulation pathway components may influence the rate of fibrosis. We hypothesised that polymorphisms of the coagulation factors II and V affect the rate of progression to cirrhosis in HCV infected subjects. METHODS: We studied the relationship between rate of fibrosis (calculated by dividing the fibrosis stage by duration of infection) and genotypes of specific coagulation pathway genes in 352 White European patients infected with HCV. Genotyping was performed using reverse line blot hybridisation. RESULTS: The rate of fibrosis was significantly higher in patients with the factor V Leiden genotype (Arg560Gln) (ANOVA, p=0.004). In disease association studies, a significant association was seen (Fisher's exact test, p=0.029; odds ratio 3.28 for fast progression to cirrhosis (expected to reach cirrhosis in less than 30 years) if heterozygous for factor V Leiden). No associations were seen between factor II genotype and fibrosis rate. CONCLUSIONS: Possession of the factor V Leiden polymorphism significantly increases the risk of rapid disease progression in HCV, suggesting a role for the coagulation system in the pathogenesis of fibrotic liver disease.
Human serum contains two isoforms of tartrate-resistant acid phosphatase (TRACP) known as TRACP 5a and TRACP 5b with pH optima of 5.0 and 5.8, respectively. Preliminary data suggest that serum TRACP 5b is derived from osteoclasts and serum TRACP 5a from some other cells. It has been reported that heparin inhibits TRACP 5a but has no effect on the activity of TRACP 5b. Here we show that heparin has no effect on serum TRACP activity, as determined using our previously published immunoassay, suggesting that the immunoassay does not detect TRACP 5a. The change of serum TRACP 5b activity after 6 months HRT, determined by this immunoassay, correlated significantly with the changes of all markers of bone turnover determined, including serum N- and C-terminal propeptides of type I collagen and urinary-free deoxypyridinoline. Serum TRACP 5b activity was significantly elevated in patients with osteoporosis and had a significant negative correlation with bone mineral density (BMD). Serum TRACP 5a activity, determined by an immunoassay, showed no correlation with serum TRACP 5b activity, with BMD, or with any of the markers of bone turnover. These results show that serum TRACP 5b, but not 5a, reflects the bone resorption rate, and that our TRACP 5b immunoassay may be a specific method for the determination of the bone resorption rate from serum samples.
AIM: To examine the time trends and seasonal patterns in asthma mortality and hospitalisations in Maori and non-Maori. METHODS: We studied asthma deaths in Maori and non-Maori during 1962-1998 and asthma hospitalisations during 1976-1998 in the 5-34 and 35-74 year age-groups. Average monthly mortality and hospital discharge rates were calculated for 1978-1998 to observe the seasonal patterns. RESULTS: The two asthma mortality epidemics of the 1960s and 1970s affected Maori disproportionately, with the peak rates in 1979 being twice that of non-Maori (7.4 vs 3.7 per 100 000) although the rates are now similar. Hospitalisation rates for Maori were consistently higher than non-Maori with the rates remaining elevated until 1987. The most recent hospitalisation figures show a fall of 61.2% from the 1987 rate. For Maori in the 5-34 year age-group, deaths were highest in spring while hospitalisations peaked in the winter month of May. CONCLUSION: Although asthma mortality and hospitalisation rates for Maori have declined over the period under study, Maori continue to experience more severe asthma and have a higher number of hospital admissions for asthma than non-Maori.
The aim of this work was to study oxidative stress and the compensating mechanisms implicated in severe thermal injury using the burned rat model. Results showed that after thermal injury glutathione (GSH) level was decreased, oxidized glutathione (GSSG) and the ratio of GSSG/GSH increased both at 24 and 48 h in the liver. The activities of GSH-reductase (GSH-Rx) in the liver and GSH-peroxidase (GSH-Px) both in the liver and erythrocytes increased at 24 h and then decreased at 48 h. The level of alpha-tocopherol in plasma was reduced at 24 h. Lipid peroxide levels increased both at 24 and 48 h in the liver. The serum zinc level decreased, reaching a minimum at 12h, whereas liver zinc level was elevated and reached the maximum at 12 h. After severe thermal injury enhancement of metallothionein (MT) expression has been discovered for the first time. MT content in the liver increased both at 24 and 48 h. Expression of MT-I mRNA was activated at 3 h and reached the top at 24 h postburn. The conclusion is that severe thermal injury gives rise to oxidative stress and dramatic enhancement of MT expression could be one of the important compensative mechanisms of natural defense system postburn.
The purpose of this intervention trial was to determine whether changes in bone mass distribution could be observed in postmenopausal women following hormone replacement therapy (HRT) and/or high-impact physical exercise. Eighty healthy women, aged 50-57 years, at <5 years after the onset of menopause and with no previous use of HRT, were randomly assigned to one of four groups: HRT; exercise (Ex); HRT + Ex (ExHRT); and control (Co). HRT administration was conducted in a double-blind manner for 1 year using estradiol plus noretisterone acetate (Kliogest). The exercise groups participated in a 1 year progressive training program consisting of jumping and bounding activities. Subjects participated in two supervised sessions per week and were asked to perform a series of exercises at home 4 days/week. Bone measurements using a quantitative computed tomography scanner (Somatom DR, Siemens) were obtained from the proximal femur, midfemur, proximal tibia, and tibial shaft. Data were analyzed with a software program (BONALYSE 1.3) calculating density (g/cm(3)), cross-sectional area (CSA; mm(2)), and moments of inertia (I(max), I(min), I(polar)). In addition, the bone mass spectrum was determined as a function of the angular distribution around the bone mass center (polar distribution) and the distance from the bone mass center through the diaphyseal wall (radial distribution). After the 1 year period, there was an overall interaction of group x time in bone mineral density (BMD) at the proximal femur (p = 0.05) and tibial shaft (p = 0.035). Women in the ExHRT and HRT groups had increased proximal femur and tibial shaft BMD when compared with the change observed in the Co group (p = 0.024-0.011). The change was more pronounced in the cortical tibia, wherein the ExHRT group also differed from the Ex group (p = 0.038). No significant changes were found in bone CSA at any of the measured sites. The radial distribution indicated an increase of BMD in the endocortical part of the measured sites in the HRT and ExHRT groups and in the proximal tibia in the Ex group. The polar distribution showed that bone mass was redistributed in the anteroposterior direction. The changes in I(max), I(min), and I(polar) in the HRT and ExHRT groups differed from those in the Co group at the proximal femur, midfemur, and proximal tibia (p = 0.047-0.001). The Ex group also differed from the Co group in I(max) and I(polar) at the proximal tibia (p = 0.018 and 0.039, respectively). These results support the idea that HRT acts primarily at the bone-marrow interface. The exercise intervention chosen for this study contributed to the maintenance of bone mass. Our results suggest that both HRT and exercise have local effects on bone mass. The change in bone mass distribution induced by HRT and exercise may play an important role in the alteration of bone strength.
The complexity of recognizing the potential contribution of a number of possible predictors of complex disorders is increasingly challenging with the application of large-scale single nucleotide polymorphism (SNP) typing. In the search for putative genetic factors predisposing to coronary artery restenosis following balloon angioplasty, we determined genotypes for 94 SNPs representing 62 candidate genes, in a prospectively assembled cohort of 342 cases and 437 controls. Using a customized coupled-logistic regression procedure accounting for both additive and interactive effects, we identified seven SNPs in seven genes that, together, showed a statistically significant association with restenosis incidence (P <0.0001), accounting for 11.6% of overall variance observed. Among them are candidate genes for cardiovascular pathophysiology (apolipoprotein-species and NOS), inflammatory response (TNF receptor and CD14), and cell-cycle control (p53 and p53-associated protein). Our results emphasize the need to account for complex multi-gene influences and interactions when assessing the molecular pathology of multifactorial medical entities.
There is considerable technological diversity among quantitative ultrasound (QUS) devices used to assess osteoporosis. Because the distance between the transducer and the footplate remains constant, the location of the calcaneus measured will vary with foot size. This study was designed to quantify the variation in bone mineral density (BMD) between a manufacturer's region of interest (ROI_M), which is fixed relative to the footplate, and an anatomical region of interest (ROI_A), which is defined as 20% of calcaneal length. The effect of foot length and width on QUS variables measured using two Food and Drug Administration cleared QUS devices, the Sahara (Hologic) and the Achilles+ (Lunar) was assessed. 26 healthy subjects (12 male and 14 female), aged 22-54 years (35.6+/-10 years) and with foot lengths of 21.5 cm to 29.7 cm (25.1+/-2.3 cm) were recruited. QUS assessments were performed at the right calcaneus. In addition, a Hologic 4500 densitometer was used to measure the BMD of the calcaneus in the ROI_M and ROI_A. The sizes of the ROIs were approximated to the sizes of the transducers of the Sahara and Achilles+ devices. The results showed a significant difference in BMD between the two ROI locations for the Sahara device (BMD 0.642+/-0.135 g cm(-2) vs 0.616+/-0.114 g cm(-2), p=0.014), but no significant difference was found in BMD between the two locations for the Achilles device (BMD 0.661+/-0.120 g cm(-2) vs 0.662+/-0.123 g cm(-2), p=0.818). At the ROI_A, there was a significant difference in BMD between the two QUS devices (p<0.001). The correlation between QUS variables and BMD was slightly higher for the ROI_M (r=0.68-0.79, since this is site-matched) than the ROI_A (r=0.59-0.70) for the Achilles device, while for the Sahara device the correlations were r=0.35-0.40 and r=0.51-0.54, respectively. The smaller ROI of the Sahara device resulted in more than 50% of the subjects having BMD differences of greater than 5% between the ROI_A and the ROI_M, compared with only 20% of the subjects on the Achilles device. ROIs containing cortical bone edge and other soft tissues were found in 58% of cases for the Achilles device and 46% of cases for the Sahara device. The greatest differences occurred in very small and very large feet. Calcaneal length correlated significantly with Sahara speed of sound (SOS), and heel width correlated significantly with Achilles SOS. Heel width also correlated significantly with Sahara broadband ultrasound attenuation (BUA) but not Achilles+ BUA. These results suggest that variation in ROI and bone size might affect the accuracy of QUS measurements, since the calcaneus is heterogeneous both in terms of its external geometry and its internal structure and density.