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PubMed2000

Improved procedures for the generation of diborane from sodium borohydride and boron trifluoride.

Improved procedures for the generation of diborane by the reaction of NaBH4 in triglyme or tetraglyme with the BF3 adducts of di-n-butyl ether, tert-butyl methyl ether, monoglyme, dioxane, and tetrahydropyran were developed. In these systems, generation of diborane requires 2-4 h at 25 degrees C (faster reactions take place at 50 degrees C). The byproduct NaBF4 precipitates from the reaction mixture at 25 degrees C as the reaction proceeds. The high-boiling glyme can be conveniently separated from the lower boiling carrier ethers by simple distillation of the latter. On the other hand, diborane was generated very slowly or not generated using the addition of each of six boron trifluoride-etherates (di-n-butyl ether, tert-butyl methyl ether, tetrahydrofuran, tetrahydropyran, dioxane, and monoglyme) to suspensions of sodium borohydride in the corresponding ether. However, diborane was generated rapidly and quantitatively by the addition of NaBH4 in triglyme (or tetraglyme) to the BF3 adduct of triglyme (or tetraglyme) at room temperature. No solid precipitation occurs during the reaction, making it convenient for large-scale applications. The pure solvent triglyme (or tetraglyme) can be easily recovered and recycled by either crystallizing or precipitating NaBF4 from the generation flask. New procedures for the generation of diborane were also developed by the reaction of NaBF4 with NaBH4 in triglyme (or tetraglyme) in the presence of Lewis acids such as AlCl3 and BCl3.

Journal Article↗
PubMed2000

Novel nitric oxide and superoxide generation inhibitors, persenone A and B, from avocado fruit.

One known, (2R)-(12Z,15Z)-2-hydroxy-4-oxoheneicosa-12,15-dien+ ++-1-yl acetate (1), and two novel compounds, persenone A (2) and B (3), have been isolated from avocado fruit (Persea americana P. Mill), as inhibitors of superoxide (O(2)(-)) and nitric oxide (NO) generation in cell culture systems. They showed marked inhibitory activities toward NO generation induced by lipopolysaccharide in combination with interferon-gamma in mouse macrophage RAW 264.7 cells. Their inhibitory potencies of NO generation (1, IC(50) = 3.6; 2, IC(50) = 1.2; and 3, IC(50) = 3.5 microM) were comparable to or higher than that of a natural NO generation inhibitor, docosahexaenoic acid (DHA; IC(50) = 4.3 microM). Furthermore, compounds 1-3 and DHA markedly suppressed tumor promoter 12-O-tetradecanoylphorbol-13-acetate-induced O(2)(-) generation in differentiated human promyelocytic HL-60 cells (1, IC(50) = 33.7; 2, IC(50) = 1.4; 3, IC(50) = 1.8; and DHA, IC(50) = 10.3 microM). It is notable that they were found to be suppressors of both NO- and O(2)(-)-generating biochemical pathways but not to be radical scavengers. The results indicate that these compounds are unique antioxidants, preferentially suppressing radical generation, and thus may be promising as effective chemopreventive agent candidates in inflammation-associated carcinogenesis.

Animals↗
PubMed1997

Generation of putative intrastrand cross-links and strand breaks in DNA by transition metal ion-mediated oxygen radical attack.

Generation of putative intrastrand cross-links and strand breaks was investigated in salmon sperm DNA exposed to Fenton-type oxygen radical-generating systems. 32P-Postlabeling analysis of DNA treated with hydrogen peroxide and either copper(II), chromium(VI), cobalt(II), iron(II), nickel(II), or vanadium(III) resulted in the detection of between four and eight radioactive TLC spots that are probably hydroxyl radical-mediated oxidative DNA lesions. The copper Fenton system generated the highest total yield of these DNA lesions (75.6 per 10(8) nucleotides), followed by cobalt (47.5), nickel (26.2), chromium (25.1), iron (21.7), and vanadium (17.1). Two spots, common to all these Fenton systems, were the major oxidation products in each case. Similar Fenton-type treatment of the purine dinucleotides dApdG and dApdA resulted in products that were chromatographically identical on anion-exchange TLC and on reverse-phase HPLC to the two major products generated in DNA. These results extend our earlier studies suggesting that these products were the result of a free radical-mediated intrastrand cross-linking reaction. Incubations involving cadmium(II), chromium(III), or zinc(II) ions with hydrogen peroxide did not generate DNA oxidation products at levels greater than in incubations with hydrogen peroxide alone. Generation of the putative intrastrand cross-links increased in a concentration-dependent manner up to 1 mM cobalt, nickel, or chromium(VI) ions. However, in experiments with copper, iron, or vanadium ions, maximum levels were obtained at 250, 150, and 150 microM, respectively, and the yield declined with higher concentrations of these three metal ions. Agarose gel electrophoresis demonstrated extensive DNA strand breakage with copper, iron, chromium(III), or vanadium, but not with nickel, chromate(VI), cobalt, cadmium, or zinc Fenton systems. The results demonstrate that generation of the putative intrastrand cross-links and strand breaks in DNA, mediated by Fenton reactions, occurs by independent mechanisms.

Animals↗
PubMed2004

The importance of the keyword-generation method in keyword mnemonics.

Keyword mnemonics is under certain conditions an effective approach for learning foreign-language vocabulary. It appears to be effective for words with high image vividness but not for words with low image vividness. In this study, two experiments were performed to assess the efficacy of a new keyword-generation procedure (peer generation). In Experiment 1, a sample of 363 high-school students was randomly into four groups. The subjects were required to learn L1 equivalents of a list of 16 Latin words (8 with high image vividness, 8 with low image vividness), using a) the rote method, or the keyword method with b) keywords and images generated and supplied by the experimenter, c) keywords and images generated by themselves, or d) keywords and images previously generated by peers (i.e., subjects with similar sociodemographic characteristics). Recall was tested immediately and one week later. For high-vivideness words, recall was significantly better in the keyword groups than the rote method group. For low-vividness words, learning method had no significant effect. Experiment 2 was basically identical, except that the word lists comprised 32 words (16 high-vividness, 16 low-vividness). In this experiment, the peer-generated-keyword group showed significantly better recall of high-vividness words than the rote method groups and the subject generated keyword group; again, however, learning method had no significant effect on recall of low-vividness words.

Adolescent↗
PubMed1990

Generation effects in free recall: further support for a three-factor theory.

A framework is presented that helps explain and predict generation effects in free recall (for between-subjects manipulations of generating vs. reading). When the targets share common features and when that shared information is salient to subjects, subjects will exploit that information to help generate the target items. This produces more relational processing among the targets (relative to reading), enhancing free recall. Consistent with this idea, when shared information (among targets) was salient, generation effects in free recall were found under encoding conditions that can disrupt generation effects in cued recall (e.g., pairing targets with unrelated cues). Further, within the same list, generation effects emerged in free recall for targets that were processed after shared information became evident but not for targets processed prior to the availability of the shared information. In recognition, generation effects were found for targets regardless of when they were processed.

Attention↗
PubMed1990

The generation effect: a test between single- and multifactor theories.

Single- and multifactor accounts of the generation effect (better memory for internally generated items than for externally presented items) were tested. Single-factor theories suggest that generation induces either stimulus-response relational processing or response-oriented processing. Multifactor theories suggest that generation induces both types of processing. In the first three experiments subjects either read or generated responses, and the degree of categorical structure within the list was manipulated. When categorical structure was minimal, large generation effects were observed for free recall and recognition, but not for cued recall. When categorical structure was high, however, a generation effect was observed for cued recall but not for recognition or free recall. A fourth experiment was performed to eliminate an uninteresting interpretation of the results. It is argued that a multifactor account is needed to explain these findings.

Attention↗
PubMed1994

Effects of hyperosmolality on ANP-stimulated cGMP generation in rat inner medullary collecting duct.

The inner medullary collecting duct (IMCD) is a major target site of atrial natriuretic peptide (ANP) for diuresis and natriuresis, and it is in a hypertonic condition made by the renal countercurrent multiplication system. We investigated the effects of hyperosmolality on ANP-stimulated cGMP generation in IMCD and glomerulus. Hypertonic solutions (490 and 690 mOsm/kg.H2O) were made by adding NaCl or urea to isotonic solution (290 mOsm/kg.H2O). Hypertonicity of 490 mOsm/kg.H2O using NaCl reduced both ANP-stimulated guanylate cyclase activity (from 7.7 +/- 1.1 to 4.1 +/- 0.5 fmol/mm/5 min) and cGMP generation (from 1.35 +/- 0.18 to 0.48 +/- 0.20 fmol/mm/3 min) in IMCD. Hypertonicity of 690 mOsm/kg.H2O using NaCl did not further reduce ANP-stimulated cGMP generation in IMCD. Hypertonicity using urea also inhibited ANP-stimulated guanylate cyclase activity and cGMP generation in IMCD. On the other hand, hypertonicity using NaCl stimulated AVP-stimulated cAMP generation in IMCD, while hypertonicity using urea reduced it. In glomeruli, hyperosmolality of 490 mOsm/kg.H2O using NaCl also reduced ANP-stimulated cGMP generation, and hypertonicity of 690 mOsm/kg.H2O using NaCl further reduced it. In summary, hyperosmolality using NaCl and urea inhibited ANP-sensitive guanylate cyclase activity and cGMP generation both in IMCD and glomeruli. However, the mechanisms at work may be different between NaCl and urea.

Animals↗
PubMed1992

Effect of seafood consumption on the urinary level of total hydride-generating arsenic compounds. Instability of arsenobetaine and arsenocholine.

Arsenobetaine and arsenocholine are considered to be non-toxic and are present as a relatively large proportion of total arsenic in seafoods, and they do not respond to hydride generation. The present study describes the effect of seafood consumption on the urinary concentration of hydride-generating arsenic compounds measured by a newly developed flow injection atomic absorption spectrometric (FI-AAS) method. Consumption of plaice, pighvar and tunny resulted in a 2-fold increase, and consumption of mussels produced a 6-fold increase in the urinary level of hydride-generating arsenic compounds. Hence, a person who has consumed mussels may be suspected of being occupationally or environmentally exposed, if the level of consumption of this seafood is unknown. As the FI-AAS method cannot be used to detect arsenobetaine and arsenocholine, the observed increase in urinary concentration of hydride-generating arsenic compounds after consumption of seafood must originate either from hydride-generating arsenic compounds in the seafood or from degraded arsenobetaine or arsenocholine. The present study has demonstrated that both arsenobetaine and arsenocholine are unstable when incubated in daylight in the presence of hydrogen peroxide, i.e., an oxidizing environment. Hence, it is tempting to speculate that arsenobetaine could be converted into hydride-generating arsenic compounds during storage or cooking of seafood. The feasibility of speciation methods based on high-performance liquid chromatographic (HPLC) separation and on-line analysis by inductively coupled plasma atomic emission spectrometry (ICP-AES) and FI-AAS was also investigated. The FI-AAS system is approximately 35 times more sensitive to the hydride-generating arsenic species than the ICP-AES system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

A functional on-chip pressure generator using solid chemical propellant for disposable lab-on-a-chip.

This paper presents a functional on-chip pressure generator that utilizes chemical energy from a solid chemical propellant to perform fluidic delivery in applications of plastic-based disposable biochips or lab-on-a-chip systems. In this functional on-chip pressure generator, azobis-isobutyronitrile (AIBN) as the solid chemical propellant is deposited on a microheater using a screen-printing technique, which can heat the AIBN at 70 degrees C to produce nitrogen gas. The output pressure of nitrogen gas, generated from the solid chemical propellant, is adjustable to a desired pressure by controlling the input power of the heater. Using this chemical energy source, the generated pressure depends on the deposited amount of the solid chemical propellant and the temperature of the microheater. Experimental measurements show that this functional on-chip pressure generator can achieve around 3 000 Pa pressure when 189 mJ of energy is applied to heat the 100 microg of AIBN. This pressure can drive 50 nl of water through a microfluidic channel of 70 mm and cross-sectional area of 100 microm x 50 microm. Due to its compact size, ease of fabrication and integration, high reliability (no moving parts), biologically inert gas output along with functionality of gas generation, this pressure generator will be an excellent pressure source for handling the fluids of disposable lab-on-a-chip, biochemical analysis systems or drug delivery systems.

Aerosol Propellants↗
PubMed1976

Role of ubiquinone in the mitochondrial generation of hydrogen peroxide.

Antimycin-inhibited bovine heart submitochondrial particles generate O2- and H2O2 with succinate as electron donor. H2O2 generation involves the action of the mitochondrial superoxide dismutase, in accordance with the McCord & Fridovich [(1969) j. biol. Chem. 244, 6049-6055] reaction mechanism. Removal of ubiquinone by acetone treatment decreases the ability of mitochondrial preparations to generate O2- and H2O2, whereas supplementation of the depleted membranes with ubiquinone enhances the peroxide-generating activity in the reconstituted membranes. Addition of superoxide dismutase to ubiquinone-reconstituted membranes is essential in order to obtain maximal rates of H2O2 generation since the acetone treatment of the membranes apparently inactivates (or removes) the mitochondrial superoxide dismutase. Parallel measurements of H2O2 production, succinate dehydrogenase and succinate-cytochrome c reductase activities show that peroxide generation by ubiquinone-supplemented membranes is a monotonous function of the reducible ubiquinone content, whereas the other two measured activities reach saturation at relatively low concentrations of reducible quinone. Alkaline treatment of submitochondrial particles causes a significant decrease in succinate dehydrogenase activity and succinate-dependent H2O2 production, which contrasts with the increase of peroxide production by the same particles with NADH as electron donor. Solubilized succinate dehydrogenase generates H2O2 at a much lower rate than the parent submitochondrial particles. It is postulated that ubisemiquinone (and ubiquinol) are chiefly responsible for the succinate-dependent peroxide production by the mitochondrial inner membrane.

Acetone↗
PubMed1987

The inhibition by diphenyleneiodonium and its analogues of superoxide generation by macrophages.

Peritoneal macrophages were elicited in rats by using casein as a stimulus; when stimulated with phorbol 12-myristate 13-acetate (PMA) they produced O2.-. Nearly 60% of the total cytochrome b had a low Em,7.0 of -247 mV, typical of the cytochrome b component found in the NADPH-dependent O2(.-)-generating oxidase of neutrophils. The rate of O2.- generation by macrophages was 1.23 mol of O2.-/s per mol of cytochrome b. Treatment of intact macrophages with diphenyleniodonium (DPI) at 0.9 microM caused 50% inhibition of PMA-induced O2.- generation, with little effect on mitochondrial respiratory activity; KCN inhibited respiratory activity without affecting PMA-induced O2.- generation. A similar specificity of inhibition was found for di-2-thienyliodonium (50% inhibition of O2.- generation at 0.5 microM) and, at higher concentrations, for diphenyl iodonium. When macrophage suspensions were incubated with [125I]DPI followed by autoradiography of SDS/polyacrylamide-gel-electrophoresis-separated polypeptides, radioactivity was most strongly associated with a band of Mr 45,000, similar to that found in neutrophils [Cross & Jones (1986) Biochem. J. 237, 111-116]. The O2(.-)-generating oxidase of macrophages appears to have components in common with the NADPH oxidase of neutrophils, despite differences in activity. Its sensitivity to DPI suggests that selective prevention of radical generation by macrophages in vivo is possible.

Animals↗
PubMed1997

Influence of SNN-6010, an elemental diet, on the generation of cytokines, NO, and chemiluminescence from leukocytes and umbilical vein endothelial cells in man.

AIMS: There is insufficient information on the influence of elemental diet (ED) on leukocytes and endothelial cells although ED has been used increasingly for debilitated and post-operative patients. We here aimed to show the influence of SNN-6010 (Twinline; TL), which contains medium-chain triglycerides, on the generation of cytokines and nitric oxide (NO) and chemiluminescence in human umbilical vein endothelial cells (HUVEC) and leukocytes. METHODS: Leukocytes were obtained from 10 healthy volunteers and 10 patients with jaw fractures who underwent TL for 30 days after intermaxillary fixation. Luminol-dependent chemiluminescence and NO generation were measured in polymorphonuclear leukocytes (PMN) and HUVEC and generation of interleukin-1 beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha), and prostaglandin E2 (PGE2) as well as expression of these cytokines' mRNA were examined in lymphocytes, monocytes, PMN, and HUVEC. RESULTS: TL dose-dependently suppressed generation of IL-1beta, TNF-alpha, PGE2, and NO in all kinds of cells from healthy individuals. Lymphocytes from patients who underwent TL feeding for 30 days showed reduced generation of IL-1beta and TNF-alpha, and the suppressed cytokine generation corresponded with the decreased expression of mRNA of these cytokines. Chemiluminescence by PMN from healthy individuals was suppressed by TL dose-dependently, and PMN from TL-fed patients showed reduced chemiluminescence. CONCLUSION: These results appear to indicate that TL suppresses the functions of leukocytes and endothelial cells by down-regulating the generation of reactive oxygen intermediates, NO, and cytokines.

Adult↗
PubMed2002

Effects of GH on lipid peroxidation and neutrophil superoxide anion-generating capacity in hypopituitary adults with GH deficiency.

OBJECTIVES: Untreated growth hormone deficiency (GHD) is implicated in the increased cardiovascular risk associated with adult hypopituitarism. Oxidative stress, predisposing to lipid peroxidation, may be an important mediator of endothelial dysfunction, a pro-atherogenic state associated with adult GHD. DESIGN AND PATIENTS: In a randomized, double-blind, placebo-controlled study we investigated the effects of GH replacement on low-density lipoprotein (LDL) oxidation and neutrophil superoxide (O(-)(2)) generating capacity in 32 GHD adults (19 males, 13 females; age range 19-64 years) over 3 months. Thirty age- and sex-matched healthy controls were also studied. MEASUREMENTS: Lipid hydroperoxides (HPOs) in plasma were measured using the ferrous oxidation with xylenol orange (FOX) assay. The susceptibility of LDL to oxidation was assessed by the copper-catalysed lag phase of LDL oxidation. Neutrophil O(-)(2)- generating capacity was assessed by a lucigenin-based chemiluminescent assay of NADPH oxidase activity. Body composition was assessed using bioelectrical impedance analysis. RESULTS: Compared to controls, GHD subjects had higher LDL cholesterol (4.0 +/- 0.8 vs. 3.5 +/- 0.9 mmol/l, P < 0.01) and higher triglyceride concentrations (2.3 +/- 1.5 vs. 1.1 +/- 0.7 mmol/l, P < 0.001) but lower HDL cholesterol (1.1 +/- 0.3 mmol/l vs. 1.4 +/- 0.4 mmol/l, P < 0.01), lower levels of HPOs (0.72 +/- 0.35 vs. 0.92 +/- 0.20 microm, P < 0.01) and lower basal (2.5 +/- 1.5 vs. 4.5 +/- 2.3 mV/5 x 10(5) neutrophils, P < 0.01) and peak post-activation levels (23.2 +/- 11.1 vs. 34.4 +/- 15.6 mV/5 x 10(5) neutrophils, P < 0.01) of neutrophil O(-)(2)- generation. GH replacement resulted in an increase in HPOs from 0.70 +/- 0.39 to 0.86 +/- 0.19 microm (P < 0.05), although there was no change in the lag time of LDL oxidation. Neutrophil O(-)(2)- generating capacity was enhanced with a rise in basal O(-)(2)- generation from 2.8 +/- 1.4 to 5.4 +/- 4.6 mV/5 x 10(5) neutrophils (P < 0.05) and in peak post-activation O(-)(2)- generation from 21.9 +/- 9.5 to 35.8 +/- 21.7 mV/5 x 10(5) neutrophils (P < 0.05). LDL cholesterol was reduced from 4.1 +/- 0.8 mmol/l to 3.5 +/- 0.8 mmol/l (P < 0.01). No significant changes in measured parameters occurred in the placebo group. CONCLUSIONS: Adult GHD is associated with reduced lipid peroxidation and impaired neutrophil O(-)(2)- generating capacity, both of which are reversible with GH replacement. Our data suggest that: (i) that oxidative stress is not a major feature of the pro-atherogenic state in hypopituitary adults with GHD and (ii) a role for GH in modulating neutrophil function and leucocyte-lipoprotein interactions.

Adult↗
PubMed2003

Optimized culture conditions for the generation of dendritic cells from peripheral blood monocytes.

BACKGROUND AND OBJECTIVES: Dendritic cells (DCs) are promising adjuvants for clinical immunotherapy, but they are scantily distributed. Therefore, numerous in vitro methods have been developed to expand these cells while maintaining their normal functions. Current culture systems generally require the use of fetal bovine serum (FBS)-supplemented media in order to attain DCs with high immunostimulatory activity. However, the presence of exogenous animal proteins sets limits for their use in clinical trials. The purpose of this study was to establish a simple, efficient and FBS-free method for the generation of human DCs for clinical application. MATERIALS AND METHODS: We compared monocyte-derived DCs generated in a standard FBS-supplemented medium vs. DCs generated in an autologous plasma (AutoPl)-supplemented medium, with regard to their yield, function and longevity. Peripheral blood monocytes were isolated from buffy coats by two consecutive 2-h adherence steps in tissue culture flasks. The adherent cells were differentiated into DCs within 2 weeks by adding granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4), c-kit ligand and tumour necrosis factor-alpha (TNF-alpha). Every 2-3 days, the cells in suspension were analysed for their immunophenotype and apoptosis rate by flow cytometry. Their function was demonstrated by their allostimulatory and migratory capacity, as well as by their proteolytic activity. RESULTS: We show that more than 30 x 10(6) DCs can be achieved per unit of buffy coat using either AutoPl- or FBS-supplemented media. The purity of the DCs was 53.4% and 65% (P > 0.05) in AutoPl- and FBS-based medium, respectively. DCs grown in AutoPl media showed a CD80high CD83+ CD86high CD14neg HLA-DR+ CD1aneg phenotype, while FBS-generated DCs exhibited a CD80high CD83+ CD86high CD14neg HLA-DR+ CD1ahigh phenotype. The apoptosis rate in both culture conditions increased from 10% to 25% over 1 week. AutoPl-generated DCs were shown to be equally strong stimulators for proliferation of allogeneic T lymphocytes as FBS-generated DCs. In addition, the capacity to migrate in response to macrophage inflammatory protein-1alpha (MIP-1alpha) and stromal-cell-derived factor 1alpha (SDF-1alpha) was similar in both groups, whereas the response to MIP-3beta was reduced in AutoPl-derived cells. Zymography analysis of supernatants from 5-day-old cultures demonstrated that AutoPl-generated DCs produced higher amounts of matrix metalloproteinases, suggesting that they have an enhanced capability to traffic through peripheral tissues. CONCLUSIONS: Our findings indicate that plastic-adherent peripheral blood cells, when cultured with GM-CSF, IL-4, c-kit-ligand and TNF-alpha in autologous human plasma-supplemented media, are a potent source of functional DCS that may be of value for human therapy.

Blood Cells↗
PubMed2000

Intracellular site of gamma-secretase cleavage for Abeta42 generation in neuro 2a cells harbouring a presenilin 1 mutation.

Previously, we reported that mutations in presenilin 1 (PS1) increased the intracellular levels of amyloid beta-protein (Abeta)42. However, it is still not known at which cellular site or how PS1 mutations exert their effect of enhancing Abeta42-gamma-secretase cleavage. In this study, to clarify the molecular mechanisms underlying this enhancement of Abeta42-gamma-secretase cleavage, we focused on determining the intracellular site of the cleavage. To address this issue, we used APP-C100 encoding the C-terminal beta-amyloid precursor protein (APP) fragment truncated at the N terminus of Abeta (C100); C100 requires only gamma-secretase cleavage to yield Abeta. Mutated PS1 (M146L)-induced Neuro 2a cells showed enhanced Abeta1-42 generation from transiently expressed C100 as well as from full-length APP, whereas the generation of Abeta1-40 was not increased. The intracellular generation of Abeta1-42 from transiently expressed C100 in both mutated PS1-induced and wild-type Neuro 2a cells was inhibited by brefeldin A. Moreover, the generation of Abeta1-42 and Abeta1-40 from a C100 mutant containing a di-lysine endoplasmic reticulum retention signal was greatly decreased, indicating that the major intracellular site of gamma-secretase cleavage is not the endoplasmic reticulum. The intracellular generation of Abeta1-42/40 from C100 was not influenced by monensin treatment, and the level of Abeta1-42/40 generated from C100 carrying a sorting signal for the trans-Golgi network was higher than that generated from wild-type C100. These results using PS1-mutation-harbouring and wild-type Neuro 2a cells suggest that Abeta42/40-gamma-secretase cleavages occur in the Golgi compartment and the trans-Golgi network, and that the PS1 mutation does not alter the intracelluar site of Abeta42-gamma-secretase cleavage in the normal APP proteolytic processing pathway.

Amyloid Precursor Protein Secretases↗
PubMed2003

Similar predictive value of bone turnover using first- and second-generation immunometric PTH assays in pediatric patients treated with peritoneal dialysis.

BACKGROUND: Accurate measurements of the concentration of parathyroid hormone (PTH) in serum or plasma are essential for the proper assessment of renal osteodystrophy. The first-generation immunometric PTH assay (1st PTH-IMA) not only detects the intact hormone, but also additional PTH fragments truncated at the amino N-terminally truncated PTH-derived fragments [ntPTH(1-84)]. A second-generation immunometric PTH assay (2nd PTH-IMA) recognizes only PTH(1-84) and possibly PTH fragments that are truncated at the carboxyl-terminus but not PTH(7-84). Whether estimates of the ratio between PTH(1-84) and ntPTH(1-84) fragments are a better predictor of bone turnover remains controversial. METHODS: Thirty-three patients aged 12.8 +/- 4.4 years treated with continuous cycling peritoneal dialysis (CCPD) for 13 +/- 9 months underwent iliac crest bone biopsy. PTH levels were measured by two newly developed first-generation and second-generation PTH-IMA. The ntPTH(1-84) fragments were calculated by subtracting PTH values determined using the 2nd PTH-IMA from values obtained using 1st PTH-IMA that detects both PTH(1-84) and relatively large ntPTH(1-84). RESULTS: Determinations of PTH levels by both assays were highly correlated (r = 0.89, P < 0.001). The relationships between first-generation and second-generation PTH-IMA and bone formation were similar (r = 0.67, P < 0.0001 and r = 0.64, P < 0.0001, respectively). When patients were grouped according to the presence or absence of secondary hyperparathyroidism, the ratio PTH(1-84) to ntPTH(1-84) did not differ between groups. CONCLUSION: PTH concentrations determined by either the first- or the second-generation PTH-IMA were found to be better predictors of bone formation than the PTH(1-84) to ntPTH(1-84) fragments ratio.

Adolescent↗
PubMed1997

Generation of interleukin 8 in stored apheresis platelet concentrates and the preventive effect of prestorage ultraviolet B radiation.

BACKGROUND: Several recent studies have reported both the generation of cytokines, including interleukin (IL)-1 beta, IL-6, tumor necrosis factor alpha (TNF-alpha), and IL-8, in the supernatants of stored platelet concentrates (PCs) and the implications of this generation in febrile nonhemolytic transfusion reactions. Prestorage filtration is regarded as highly effective in the prevention of cytokine generation. STUDY DESIGN AND METHODS: Studies evaluated 1) the levels of these cytokines in apheresis PCs during storage, 2) the effects of white cell inactivation by ultraviolet B or gamma-radiation on the generation of cytokines, and 3) the effects of poststorage filtration on cytokine levels. The apheresis PCs were treated by either ultraviolet B radiation (20,000 J/m2), gamma-radiation (30 Gy), or filtration. Samples were collected sequentially on various days after storage. Cytokines were determined by enzyme-linked immunosorbent assay. RESULTS: The average white cell count in 15 PCs tested was 2.58 +/- 0.7 x 10(6) per mL (range, 0.7-10 x 10(6)/mL). A detectable level of IL-8 was found at 3 days of storage, and the levels of this cytokine increased progressively with increasing storage time, ranging from 1.6 to 35,280 pg per mL on Day 5 and from 2.7 to 83,601 pg per mL on Day 8. Reverse transcriptase-polymerase chain reaction analysis showed that the level of IL-8 paralleled the expression of IL-8 transcripts. The levels of IL-1 beta, IL-6, TNF-alpha, and monocyte chemotactic protein-1 were very low, even on Day 8. Ultraviolet B-radiated PCs failed to generate IL-8, even at 8 days of storage, whereas levels of IL-8 in gamma-radiated PCs were similar to those in nonirradiated PCs. Poststorage filtration of PCs with a negatively charged polyester filter, but not with a positively charged one, markedly reduced the levels of IL-8. CONCLUSION: Of the cytokines tested, IL-8 had the most evident generation in apheresis PCs during storage. Prestorage inactivation of white cells by ultraviolet B radiation, but not by gamma-radiation, was effective in preventing the generation of cytokines during the storage of PCs.

Anaphylatoxins↗
PubMed1997

Performance of three generations of anti-hepatitis C virus enzyme-linked immunosorbent assays in donors and patients.

BACKGROUND: Prevention of posttransfusion non-A,non-B hepatitis in recipients of blood components improved considerably with the introduction of the second-generation of hepatitis C virus (HCV) antibody tests. In 1993, third-generation HCV antibody assays were introduced in Europe. STUDY DESIGN AND METHODS: The performance of three generations of anti-HCV enzyme-linked immunosorbent assay (ELISA) (ELISA-1, -2, -3) was compared in routine blood donor screening (99,394 donations were tested with ELISA-1, 167,999 donations with ELISA-2, and 262,090 donations with ELISA-3) and in serial samples from nine patients with documented acute posttransfusion HCV infection. RESULTS: Eight (0.01%) repeat donors, previously negative in ELISA-1, were found positive in ELISA-2 and were confirmed as positive in second-generation recombinant immunoblot assay and/or cDNA polymerase chain reaction. In the donor population, no difference in the sensitivity of ELISA-2 and -3 was observed. The specificity of the three generations of ELISAs was comparable (99.8, 99.7, and 99.7%). In seroconversion samples, ELISA-2 and -3 detected HCV antibodies at the same time in seven patients, but in two patients, ELISA-3 found HCV antibodies, respectively, 63 and 77 days earlier than ELISA-2 did. In the seroconversion samples, ELISA-2 and -3 were significantly more sensitive than second- and third-generation recombinant immunoblot assays. CONCLUSION: ELISA-3 did not detect more HCV-infected individuals in a donor population that previously tested negative in ELISA-2, but it did detect HCV antibodies earlier in some patients with acute HCV infection. ELISA-2 and -3 were significantly more sensitive than second- and third-generation recombinant immunoblot assays.

Blood Donors↗