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4-hydroxynonenal (HNE), a highly reactive lipid peroxidation product, may adversely modify proteins. Accumulation of HNE-modified proteins may be responsible for pathological lesions associated with oxidative stress. The objective of this work was to determine how HNE-modified proteins are removed from cells. The data showed that alphaB-crystallin modified by HNE was ubiquitinated at a faster rate than that of native alphaB-crystallin in a cell-free system. However, its susceptibility to proteasome-dependent degradation in the cell-free system did not increase. When delivered into cultured lens epithelial cells, HNE-modified alphaB-crystallin was degraded at a faster rate than that of unmodified alphaB-crystallin. Inhibition of the lysosomal activity stabilized HNE-modified alphaB-crystallin, but inhibition of the proteasome activity alone had little effect. To determine if other HNE-modified proteins are also degraded in a ubiquitin-dependent lysosomal pathway, lens epithelial cells were treated with HNE and the removal of HNE-modified proteins in the cells was monitored. The levels of HNE-modified proteins in the cell decreased rapidly upon removal of HNE from the medium. Depletion of ATP or the presence of MG132, a proteasome/lysosome inhibitor, resulted in stabilization of HNE-modified proteins. However, proteasome-specific inhibitors, lactacystin-beta-lactone and epoxomicin, could not stabilize HNE-modified proteins in the cells. In contrast, chloroquine, a lysosome inhibitor, stabilized HNE-modified proteins. The enrichment of HNE-modified proteins in the fraction of ubiquitin conjugates suggests that HNE-modified proteins are preferentially ubiquitinated. Taken together, these findings show that HNE-modified proteins are degraded via a novel ubiquitin and lysosomal-dependent but proteasome-independent pathway.
The objective of this study was to learn the property of poly-hydroxybutyrate membrane (PHBm) modified by gamma-radiation and mixture of calcium sulfate, and to explore the possibility of using modified PHBm for guided tissue regeneration (GTR). The PHB was treated by 5 KGy gamma-radiation and mixed with 1/10 calcium sulfate. The modified PHB membrane was prepared by solvent-casting techniques. The mechanical properties and molecular weight of the modified PHBm were tested. Degradability of the modified PHBm was analyzed in vitro in a buffer solution of KH2PO4-Na2HPO4. Biodegradability and biocompatibility of the modified PHBm were inspected 1, 2, 3 and 6 months after the embedding of the modified PHBm into dogs. The morphology was analyzed by scanning electron microscopy (SEM) and molecular weight was tested to evaluate the biodegradability of PHBm. Biocompatibility of the modified PHBm was observed through tissue response by light microscopy. The extension strength and the extension strain at fracture of the modified PHBm were 23.8 MPa and 1.0% respectively. The morphologic observation of the modified PHBm at different terms showed that the modified PHBm was biodegraded gradually in vitro and in vivo. The capsule surrounding the modified PHBm was mainly composed of fibrocytes and few lymphocytes. The longer the time elapsed, the thinner the capsule enveloping the modified PHBm grew. The modified PHBm possesses satisfactory mechanical properties and biocompatibility, and it is biodegradable in vitro and in vivo. The modified PHB membrane could be applied as GTR membrane.
BACKGROUND: A murine monoclonal antibody designated Z2D3 (IgM) generated against homogenized human atherosclerotic plaques was demonstrated to be highly specific for proliferating smooth muscle cells. The primary clone subsequently was genetically engineered to provide a mouse/human chimeric antibody with human IgG1 constant region expressed in a rat myeloma cell line. The resulting Z2D3-73.30 chimeric retained the immunoreactivity relative to the parent Z2D3-IgM and was pepsin-digested to yield F(ab')2. 111In-labeled chimeric Z2D3 F(ab')2 was then used for noninvasive imaging of experimental atherosclerotic lesions. To improve the imaging characteristics, we modified chimeric Z2D3 F(ab')2 fragments to carry a high negative charge. Improved visualization of targets with 111In-labeled, negatively charged, polymer-modified antibodies most probably is the result of faster blood clearance and a decrease in nontarget background activity. METHODS AND RESULTS: Experimental atherosclerotic lesions were induced in rabbits by deendothelialization of the infradiaphragmatic aorta followed by a 6% peanut oil-2% cholesterol diet. After 12 weeks, localization of the conventionally labeled 111In-Z2D3 F(ab')2 (24 Mbq [650 microCi]/500 to 750 micrograms) (n = 4) was compared with 111In-labeled, negatively charged, polymer-modified Z2D3 F(ab')2 (24 Mbq [650 microCi]/25 to 50 micrograms) in eight atherosclerotic rabbits. Three control rabbits also received radiolabeled polymer-modified Z2D3. Ten rabbits with atherosclerotic lesions received 111In-labeled nonspecific human IgG1 F(ab')2 with (n = 6) or without (n = 4) negative charge modification. Atherosclerotic lesions were visualized in all rabbits with the conventional Z2D3 F(ab')2 at 48 hours. However, unequivocal lesion visualization was possible at 24 hours only with negatively charged, polymer-modified Z2D3 F(ab')2. Quantitative uptake of F(ab')2 fragments was essentially determined by the presence of atherosclerotic lesions (F1.37 = 69.8; P < .0001) and the specificity of the antibody (F1.37 = 36.6; P < .0001). Uptake of the conventional Z2D3 in atherosclerotic lesions (mean +/- SEM percent injected dose per gram, 0.112 +/- 0.024%) was six times higher than background activity in the normal aortic segments (nondenuded thoracic aorta; mean percent injected dose per gram, 0.019 +/- 0.003%). Uptake of the conventional Z2D3 was also significantly higher than that of nonspecific human IgG1 F(ab')2 (0.027 +/- 0.004%). Specific uptake of the conventional Z2D3 in the lesions was comparable to the charge-modified Z2D3 uptake (0.084 +/- 0.017; P = .20). Uptake of negative charge-modified Z2D3 in the lesions was significantly higher than in the corresponding background activity in normal thoracic aorta (0.021 +/- 0.002). Uptake of negative charge-modified Z2D3 F(ab')2 in the lesions was higher than the uptake of negative charge-modified nonspecific IgG1 F(ab')2 (0.020 +/- 0.002) in the lesions. Uptake of charge-modified Z2D3 in the atherosclerotic lesions was also significantly higher than the corresponding regions of the aorta of the control rabbits (0.017 +/- 0.002; F1.18 = 27.9; P = .0001). There was, however, no difference in the specific lesion uptake of negative charge-modified Z2D3 at 24 hours (0.079 +/- 0.014) and 48 hours (0.084 +/- 0.0017; P = .99) after intravenous administration. Nontarget organ activities were lower with negative charge-modified 111In-labeled Z2D3 F(ab')2 than with the conventional Z2D3 F(ab')2. Mean kidney activity was fourfold less with the modified (0.45 +/- 0.06) than with the conventionally radiolabeled (1.67 +/- 0.264; P = .001) Z2D3 F(ab')2.
Normal physiological clearance of gut-derived endotoxin lipopolysaccharide [LPS] has been described previously; initially, there is uptake by Kupffer cells (KC), then release of modified LPS, followed by hepatocyte uptake. Previous work in our laboratories indicated that LPS is structurally modified with loss of carbohydrate prior to its release by KC. In this study, we functionally characterize KC modified LPS. KC-modified 125I-LPS was prepared from primary rat KC. Escherichia coli 0127:B8 native 125I-LPS or KC-modified 125I-LPS (40 ng) was incubated for 1 hr with 1 x 10E6 primary hepatocytes. The binding of KC-modified LPS was 4.33-fold higher than native LPS (P = 0.0024). Binding analysis studies were conducted to determine the region of KC-modified LPS responsible for enhanced hepatocyte binding. KC-modified Salmonella minnesota LPS was competed with 100-fold excess native or mutant (Ra, Rc, Rd, or Re) strains of LPS or Lipid A with no decrease to hepatocyte binding. S. minnesota-native 125I-LPS was compared with KC-modified 125I-LPS in a study to assess induction of tumor necrosis factor (TNF)-gamma by rat peritoneal macrophages. Native or KC-modified 125I-LPS (100 ng) was presented to 1 x 10E7 peritoneal macrophages for 6 hr. TNF-alpha was measured in supernatants using the WEHI-164 cytotoxicity assay. Native LPS induced 5.7-fold higher TNF-alpha levels than KC-modified LPS (P < 0.0001). The above data suggest that structural alterations in KC-modified LPS are accompanied by functional alterations resulting in enhanced hepatocyte binding and decreased TNF-alpha release. The latter result implies that an early step in LPS detoxification occurs in the KC in which LPS is modified to prevent elicitation of biologically active cytokines.
Both labelling and traceability of genetically modified organisms are current issues that are considered in trade and regulation. Currently, labelling of genetically modified foods containing detectable transgenic material is required by EU legislation. A proposed package of legislation would extend this labelling to foods without any traces of transgenics. These new legislations would also impose labelling and a traceability system based on documentation throughout the food and feed manufacture system. The regulatory issues of risk analysis and labelling are currently harmonised by Codex Alimentarius. The implementation and maintenance of the regulations necessitates sampling protocols and analytical methodologies that allow for accurate determination of the content of genetically modified organisms within a food and feed sample. Current methodologies for the analysis of genetically modified organisms are focused on either one of two targets, the transgenic DNA inserted- or the novel protein(s) expressed- in a genetically modified product. For most DNA-based detection methods, the polymerase chain reaction is employed. Items that need consideration in the use of DNA-based detection methods include the specificity, sensitivity, matrix effects, internal reference DNA, availability of external reference materials, hemizygosity versus homozygosity, extrachromosomal DNA, and international harmonisation. For most protein-based methods, enzyme-linked immunosorbent assays with antibodies binding the novel protein are employed. Consideration should be given to the selection of the antigen bound by the antibody, accuracy, validation, and matrix effects. Currently, validation of detection methods for analysis of genetically modified organisms is taking place. In addition, new methodologies are developed, including the use of microarrays, mass spectrometry, and surface plasmon resonance. Challenges for GMO detection include the detection of transgenic material in materials with varying chromosome numbers. The existing and proposed regulatory EU requirements for traceability of genetically modified products fit within a broader tendency towards traceability of foods in general and, commercially, towards products that can be distinguished from each other. Traceability systems document the history of a product and may serve the purpose of both marketing and health protection. In this framework, segregation and identity preservation systems allow for the separation of genetically modified and non-modified products from "farm to fork". Implementation of these systems comes with specific technical requirements for each particular step of the food processing chain. In addition, the feasibility of traceability systems depends on a number of factors, including unique identifiers for each genetically modified product, detection methods, permissible levels of contamination, and financial costs. In conclusion, progress has been achieved in the field of sampling, detection, and traceability of genetically modified products, while some issues remain to be solved. For success, much will depend on the threshold level for adventitious contamination set by legislation.
Immunizing patients with metastatic melanoma by injection of autologous tumor cells modified by DNP induces inflammatory responses in metastatic masses, which is sometimes associated with tumor regression. To elucidate this phenomenon, we studied the immune response to DNP-modified cells in these patients. All developed DTH to DNP-modified autologous lymphocytes (mean +/- SE: 13.3 +/- 1.3 mm), but not to TNP-modified lymphocytes. Larger responses (21.9 +/- 3.6 mm) were elicited by DNP-modified autologous melanoma cells. In 8/11 patients tested, PBL proliferated in vitro when stimulated by autologous DNP-modified lymphocytes, and in 5 patients the stimulation resulted in production of interferon-gamma. DNP-modified autologous melanoma cells elicited lymphocyte responses as well. PBL from 1 patient were expanded by culture in IL2 and repeated restimulation with DNP-modified B lymphoblastoid cells. This T cell line proliferated and produced interferon-gamma but not IL4, when stimulated by autologous DNP-modified lymphocytes or melanoma cells. Both CD4+ and CD8+ subpopulations responded as determined by panning experiments and by testing of phenotypically homogeneous cultures obtained by limiting dilution. Studies of a stable CD8+ subline of the expanded T cells indicated that the response to DNP-modified cells was MHC-restricted, since it was blocked by antibody to class I determinants. Moreover, these T cells were able to respond to allogeneic DNP-modified stimulators that were matched at one or both HLA-A loci, but not to stimulators that were HLA-A mismatched. Finally, the CD8+ subline killed DNP-modified autologous melanoma cells, but not an HLA-A mismatched allogeneic melanoma, in a 6-hr 51Cr-release assay. These results may have significant implications for understanding the pathogenesis of drug-induced autoimmunity and for the development of new approaches to cancer immunotherapy.
Low-density lipoproteins (LDL) were modified by incubation with very-low-density lipoproteins (VLDL) and lipid transfer protein(s) to yield LDL particles that were enriched in triacylglycerol, depleted in cholesteryl esters, and contained apolipoprotein C. The uptake and degradation of these 125I-labeled modified LDL particles by cultured skin fibroblasts was reduced by approx. 30% when compared with LDL that had not been exposed to lipid transfer protein. Incubation of fibroblasts for 24 h in the presence of modified LDL resulted in less inhibition of LDL receptor activity and sterol synthesis than did incubation with control LDL. Both the degradation of 125I-labeled modified LDL and the effect of unlabeled modified LDL on the regulation of LDL binding and sterol synthesis were progressively decreased as the extent of modification of the LDL was increased. Even when identical amounts of modified LDL or control LDL protein were degraded, less inhibition of LDL receptor activity and sterol synthesis was observed with modified LDL than with control LDL, suggesting that the effects of modified LDL on these regulatory events are related to both the reduced degradation of the modified lipoprotein particles and to the alteration in its chemical composition. Uptake and degradation of modified LDL by human monocyte-derived macrophages in culture was reduced in a manner similar to that observed in the cultured fibroblasts, and was considerably less than that observed with acetylated LDL. No differences were observed between modified LDL prepared by exposure to lipid transfer activity in the lipoprotein deficient fraction of serum or when partially purified lipid transfer was used. Modified LDL, with similar composition to that used in the experiments, has been observed in certain diabetic and non-diabetic hypertriglyceridemic states. Thus, it is possible that the cellular metabolism of LDL in vivo might be altered in the presence of hypertriglyceridemia.
Post-translational modification by the conjugation of small ubiquitin-like modifiers is an essential mechanism to affect protein function. Currently, only a limited number of substrates are known for most of these modifiers, thus limiting our knowledge of their role and relevance for cellular physiology. Here, we report the development of a universal strategy for proteomic studies of ubiquitin-like modifiers. This strategy involves the development of stable transfected cell lines expressing a double-tagged modifier under the control of a tightly negatively regulated promoter, the induction of the expression and conjugation of the tagged modifier to cellular proteins, the tandem affinity purification of the pool of proteins covalently modified by the tagged modifier, and the identification of the modified proteins by LC and MS. By applying this methodology to the proteomic analysis of SUMO-1 and SUMO-3, we determined that SUMO-1 and SUMO-3 are stable proteins exhibiting half-lives of over 20 h, demonstrated that sumoylation with both SUMO-1 and SUMO-3 is greatly stimulated by MG-132 and heat shock treatment, demonstrated the preferential usage of either SUMO-1 or SUMO-3 for some known SUMO substrates, and identified 122 putative SUMO substrates of which only 27 appeared to be modified by both SUMO-1 and SUMO-3. This limited overlapping in the subset of proteins modified by SUMO-1 and SUMO-3 supports that the SUMO paralogues are likely to be functionally distinct. Three of the novel putative SUMO substrates identified, namely the polypyrimidine tract-binding protein-associated splicing factor PSF, the structural microtubular component alpha-tubulin, and the GTP-binding nuclear protein Ran, were confirmed as authentic SUMO substrates. The application of this universal strategy to the identification of the pool of cellular substrates modified by other ubiquitin-like modifiers will dramatically increase our knowledge of the biological role of the different ubiquitin-like conjugations systems in the cell.
This paper describes how default dermal exposure values can be adjusted with modifier values for specific work situations. The work presented here is supplementary to a toolkit developed for the EU RISKOFDERM project. This toolkit is intended for the assessment and management of dermal risks in small and medium sized enterprises. Potential dermal exposure (on the outer envelope of the body) is estimated with an algorithm whereby modifier values are applied multiplicatively to dermal default exposure values. These exposure modifiers with their assigned factors are intended to increase or decrease the potential (default) dermal exposure accordingly. Default estimates are modified to obtain two modified defaults: potential exposure rate to the hands and to the body. Quantitative exposure data is at present inadequate and insufficient to derive meaningful information that can be used for the selection of independent modifiers and the assignment of appropriate values. Instead, available information from the literature was considered and, in combination with expert judgement, 15 potential dermal modifiers were selected. Modifiers were classified and grouped into non-overlapping groups in order to avoid double scoring. Values were assigned to modifiers in three different exposure routes, i.e. direct contact, surface contact and deposition. Depending on the significance of a modifier, the values assigned to modifiers were weighted in equal steps on a log-scale. The values assigned to modifiers as presented in this paper are open to validation and revision once new data become available.
BACKGROUND: Prostate cancer is the most common cancer diagnosed in U.S. men and remains incurable once it has metastasized. Many stages of the metastatic cascade involve cellular interactions mediated by cell surface components, such as carbohydrate-binding proteins, including galactoside-binding lectins (galectins). Modified citrus pectin (pH-modified), a soluble component of plant fiber derived from citrus fruit, has been shown to interfere with cell-cell interactions mediated by cell surface carbohydrate-binding galectin-3 molecules. PURPOSE: The aim of this study was to determine whether modified citrus pectin, a complex polysaccharide rich in galactosyl residues, could inhibit spontaneous metastasis of prostate adenocarcinoma cells in the rat. METHODS: The ability of modified citrus pectin to inhibit the adhesion of Dunning rat prostate cancer MAT-LyLu cells to rat endothelial cells was measured by 51Cr-labeling. Modified citrus pectin inhibition of MAT-LyLu cell anchorage-independent growth was measured by colony formation in agarose. The presence of galectin-3 in rat MAT-LyLu cells and human prostate carcinoma was demonstrated by immunoblotting and immunohistochemistry. One million MAT-LyLu cells were injected subcutaneously into the hind limb of male Copenhagen rats on day 0. Rats were given 0.0%, 0.01%, 0.1%, or 1.0% (wt/vol) modified citrus pectin continuously in their drinking water (from day 4 until necropsy on day 30). The number of MAT-LyLu tumor colonies in the lungs were counted. RESULTS: Compared with 15 or 16 control rats that had lung metastases on day 30, seven of 14 rats in the 0.1% and nine of 16 rats in the 1.0% modified citrus-pectin group had statistically significant (two-sided; P < .03 and P < .001, respectively) reductions in lung metastases. The lungs of the 1.0% modified citrus pectin-treated rats had significantly (two-sided; P < .05) fewer metastatic colonies than control groups (9 colonies +/- 4 [mean +/- SE] in the control group compared with 1 colony +/- 1 in the treated group). Modified citrus pectin had no effect on the growth of the primary tumors. In vitro, modified citrus pectin inhibited MAT-LyLu cell adhesion to rat endothelial cells in a time- and dose-dependent manner as well as their colony formation in semisolid medium. CONCLUSIONS: We present a novel therapy in which oral intake of modified citrus pectin acts as a potent inhibitor of spontaneous prostate carcinoma metastasis in the Copenhagen rat. IMPLICATIONS: Further investigations are warranted to determine the following: 1) the role of galectin-3 in normal and cancerous prostate tissues and 2) the ability of modified citrus pectin to inhibit human prostate metastasis in nude mice.
BACKGROUND: The introduction of leukotriene modifiers, the first novel class of medications for asthma in more than 2 decades, provided an opportunity to evaluate the clinical context in which patients receive new treatments. Because milder asthma is usually controllable with more familiar medications, we hypothesized that adults with asthma would receive leukotriene modifiers for more severe disease. METHODS: We conducted a prospective, longitudinal, 18-month cohort study of 349 patients with asthma. We evaluated the association of baseline self-reported medication use and measures of asthma severity. We also examined the impact of baseline measurement of asthma severity on incident leukotriene modifier use at follow-up. RESULTS: At baseline, 39 (11%) of 349 patients reported leukotriene modifier use during the previous 2 weeks (95% confidence interval [CI], 8%-15%). Adults with asthma who reported recent use of leukotriene modifiers were more likely to indicate use of other long-term controller medications for asthma, such as inhaled corticosteroids (80% vs 57%;P =.007). Leukotriene modifier use was also associated with poorer severity-of-asthma scores (mean score difference, 3.6 points; 95% CI, 1.7-5.2 points) and asthma-specific health-related quality of life (mean score difference, 8.1 points; 95% CI, 3.4-12.8 points). Leukotriene modifier users were also more likely to indicate a recent emergency department visit (odds ratio [OR], 2.3; 95% CI, 0.9-5.6) or hospitalization for asthma (OR, 4.1; 95% CI, 1.4-11.4). Greater baseline asthma severity was associated with an increased probability of new-onset leukotriene modifier use during 18-month follow-up. Poorer baseline severity-of-asthma scores and asthma-specific quality-of-life scores were related to a greater likelihood of leukotriene modifier use at follow-up (OR per SD-sized score increment, 2.0; 95% CI, 1.4-2.7; OR, 1.8; 95% CI, 1.3-2.5; respectively). Recent hospitalization for asthma at baseline was also associated with a greater likelihood of leukotriene modifier use at follow-up (OR, 4.9; 95% CI, 1.6-14.8). CONCLUSIONS: Adults with asthma who receive leukotriene modifiers have more severe asthma.
Influences of seven organic modifiers, including urea, methanol (MeOH), dioxane (DIO), tetrahydrofuran (THF), acetonitrile (ACN), 1-propanol (1-PrOH) and 2-propanol (2-PrOH), on the solute retention and the electrokinetic migrations in micellar electrokinetic capillary chromatography (MEKC) are investigated with sodium dodecyl sulfate (SDS) micelle as pseudostationary phase. It is observed that in the limited concentration ranges used in the MEKC systems the effect of organic modifier concentration on the retention can be described by the equation logk1=logk1w-SC for most binary aqueous-organic buffer, but deviations from this retention equation are observed at ACN and particularly THF as organic modifiers. With parameter S as a measure of the elutropic strength, the elutropic strength of the organic modifiers is found to follow a general order urea <MeOH<ACN<2-PrOH<DIO, while THF is found to be the most abundant modifier in selectivity among the organic modifiers studied. The electroosmotic mobility decreases linearly with increasing modifier concentrations. The strength of modifiers to suppress the electroosmotic mobility follows the order urea < MeOH, ACN < DIO, THF, 1-PrOH, 2-PrOH. The addition of ACN affects the electrophoretic mobility of the SDS micelle in different patterns depending on the buffer composition used, while the addition of the other modifiers leads to a rough linear decrease of the electrophoretic mobility of the SDS micelle. The suppressing strength of THF on the electrophoretic mobility of the SDS micelle is strongly related to the buffer composition, whereas the suppressing strength for the other modifiers follows the sequence urea < MeOH < DIO, 1-PrOH, 2-PrOH. The migration time window is expanded by the use of organic modifiers. Urea and MeOH have the least expanding strength while ACN, DIO, THF, 1-PrOH and 2-PrOH have the highest expanding strength on the migration time window.
PURPOSE: To date, no measures of fecal incontinence severity or its impact on quality of life have been validated for telephone interview. This study was designed to 1) compare responses of a self-administered and a telephone-administered Fecal Incontinence Severity Index; 2) compare a self-administered Fecal Incontinence Quality of Life Scale to the Manchester Health Questionnaire after modifying the latter for telephone administration and American English (Modified Manchester Health Questionnaire); 3) assess test-retest reliability of the telephone-administered Modified Manchester Health Questionnaire; and 4) assess the internal consistency of the Modified Manchester Health Questionnaire subscales. METHODS: Consecutive, English-speaking, nonpregnant females known to have fecal incontinence were invited to participate. Two validated paper questionnaires accompanied the letter informing them of the study: Fecal Incontinence Severity Index and Fecal Incontinence Quality of Life Scale. Consenting patients were contacted for the initial telephone administration of the Modified Manchester Health Questionnaire, and patients who agreed to continue the study were contacted for a repeat telephone administration of the Modified Manchester Health Questionnaire two to four weeks after completing the first interview. RESULTS: Fifty-one females were invited to participate in the study; however, 13 declined or were ineligible. Thirty females, aged 49.3 +/- 10.3 years, returned self-administered questionnaires and completed the first telephone interview, and 21 completed a second telephone interview after an average interval of 23 days. The telephone-administered Fecal Incontinence Severity Index scores were significantly lower than those yielded by the self-administered Fecal Incontinence Severity Index, (6.19 vs. 9.85; P < 0.001), but the telephone and written administrations were significantly correlated (r = 0.5; P < 0.02). Correlations between the Modified Manchester Health Questionnaire quality of life subscales and the paper Fecal Incontinence Quality of Life subscales ranged from 0.6 to 0.9 (median, r = 0.81). The correlation between the total score for the Fecal Incontinence Quality of Life and the total score for the Modified Manchester Health Questionnaire quality of life scales was 0.93 (P < 0.001). Test-retest reliability for the eight Modified Manchester Health Questionnaire subscales ranged from 0.55 to 0.98 (median, r = 0.83), and test-retest reliability for the two telephone administrations of the Fecal Incontinence Severity Index was r = 0.75. Cronbach's alpha for the eight Modified Manchester Health Questionnaire subscales ranged from 0.79 to 0.92 (median, alpha = 0.85). CONCLUSIONS: Telephone-administered versions of the Modified Manchester Health Questionnaire showed good-to-excellent validity, internal consistency, and test-retest reliability. The telephone-administered Fecal Incontinence Severity Index yielded lower severity scores than the written Fecal Incontinence Severity Index; however, the difference (3.66 units) was not clinically significant.
This paper builds on the preceding researches to study the effects of the type of clays (montmorillonites K10, KSF) and modifying conditions on the structure and adsorption behavior of resulting clay adsorbents. The raw clays were modified by polymeric Al/Fe species, hexadecyl-trimethylammonium (HDTMA) surfactant and a complex of polymeric Al/Fe-HDTMA. X-ray diffraction spectra was applied to analyze the structure of the raw and modified clays. After modification, the basal spacing of the clays varied, depending on the types of raw clay and modification conditions. Copper and phenol were selected as adsorbates for evaluating the adsorption performance of various clays, which was affected significantly by the types of raw clay and modification conditions. In general the inorganic contaminant (e.g., Cu) tend to be adsorbed by the polymeric Al/Fe modified clay and the organic impurities (e.g., phenol) will be preferably captured by the surfactant modified clay; both due to the specific surface properties resulting from introducing the modifiers. The complex modified clays possessed the ability of adsorbing both inorganic and organic contaminants. In addition, the d 0 0 1 spacing of modified KSF was greater than that of K10; the adsorption performance with modified KSF was thus greater than that with the modified K10. Finally, the ratio of modifiers to the clay (metal:surfactant:clay) has been observed to affect the adsorption performance; the optimal conditions have been defined.
Alkaloid-modified, voltage-dependent sodium channels from lobster walking leg nerves were studied in planar neutral lipid bilayers. In symmetrical 0.5 M NaCl the single channel conductance of veratridine (VTD) (10 pS) was less than that of batrachotoxin (BTX) (16 pS) modified channels. At positive potentials, VTD- but not BTX-modified channels remained open at a flickery substate. VTD-modified channels underwent closures on the order of milliseconds (fast process), seconds (slow process), and minutes. The channel fractional open time (f(o)) due to the fast process, the slow process, and all channel closures (overall f(o)) increased with depolarization. The fast process had a midpoint potential (V(a)) of -122 mV and an apparent gating charge (z(a)) of 2.9, and the slow process had a V(a) of -95 mV and a z(a) of 1.6. The overall f(o) was predominantly determined by closures on the order of minutes, and had a V(a) of about -24 mV and a shallow voltage dependence (z(a) approximately 0.7). Augmenting the VTD concentration increased the overall f(o) without changing the number of detectable channels. However, the occurrence of closures on the order of minutes persisted even at super-saturating concentrations of VTD. The occurrence of these long closures was nonrandom and the level of nonrandomness was usually unaffected by the number of channels, suggesting that channel behavior was nonindependent. BTX-modified channels also underwent closures on the order of milliseconds, seconds, and minutes. Their characterization, however, was complicated by the apparent low BTX binding affinity and by an apparent high binding reversibility (channel disappearance) of BTX to these channels. VTD- but not BTX-modified channels inactivated slowly at high positive potentials (greater than +30 mV). Single channel conductance versus NaCl concentrations saturated at high NaCl concentrations and was non-Langmuirian at low NaCl concentrations. At all NaCl concentrations the conductance of VTD-modified channels was lower than that of BTX-modified channels. However, this difference in conductance decreased as NaCl concentrations neared zero, approaching the same limiting value. The permeability ratio of sodium over potassium obtained under mixed ionic conditions was similar for VTD (2.46)- and BTX (2.48)-modified channels, whereas that obtained under bi-ionic conditions was lower for VTD (1.83)- than for BTX (2.70)-modified channels. Tetrodotoxin blocked these alkaloid-modified channels with an apparent binding affinity in the nanomolar range.