bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of laminin chains by central neurons: Analysis with gene and protein trapping techniques
Authors: Yin Yong , Kikkawa Yamato , Mudd Jacqueline L. , Skarnes William C. , Sanes Joshua R. , Miner Jeffrey H. 
Published: June 2003

AbstractSummary: Laminins exert numerous effects on neurons in vitro, but expression of laminin subunit genes by neurons in vivo remains controversial. To reexamine this issue, we generated mice from ES cells in which the laminin α1, α5, β1, and γ1 genes had been “trapped” by insertion of a histochemically detectable selectable marker, βgeo (β‐galactosidase fused to neomycin phosphotransferase). The presence of laminin‐βgeo fusion proteins was assayed histochemically and immunochemically, revealing expression of laminin β1 and γ1 genes, but not α chain genes, by defined subsets of neurons in brain and retina. We also used the gene traps in a novel way to assay expression of endogenous laminin subunits, which were barely detectable by ordinary immunohistochemical methods. The trapping vector included a transmembrane domain that anchors proteins otherwise destined for secretion. Laminin α/β/γ heterotrimers are assembled intracellularly, and we show that the trapped laminin γ1 fusion protein “co‐trapped” endogenous β1 intracellularly. The laminin γ1 fusion was also able to co‐trap transgene‐derived α chains, but we detected no co‐trapped endogenous α chains. The co‐trapping method may be generally useful for identifying proteins or isolating protein complexes associated with trapped gene products. genesis 36:114–127, 2003. © 2003 Wiley‐Liss, Inc.
Ethical aspects of technical safety
Authors: Gethmann Carl Friedrich 
Published: June 2003

AbstractUncertainty and inequality are the most important phenomena that lead to the situation in which the modern technical age, in contrast to the premodern technical phase, gives rise to specifically moral problems which in the premodern era played only a marginal role or no role at all. So modern, technically constituted societies must learn to develop from the initial perception of dangers to a rational risk assessment. To justify this ethical obligation, the first section discusses the relation between danger and risk. The problem of weighing risks is analyzed in the second section; in this context the concept of pragmatic consistency is introduced. In the third section, the term safety is explicated as a comparative concept by means of the principle of pragmatic consistency. © 2003 Wiley Periodicals, Inc. Hum Factors Man 13: 243–252, 2003.
Changes in expression and activity of glutathione S‐transferase in different organs of schistosoma haematobium‐infected hamster
Authors: Sheweita S. A. , Mostafa M. H. , Ebid F. , El‐Sayed W. 
Published: June 2003

AbstractSchistosomiasis is a major health problem in many subtropical developing countries, causing a number of serious pathologies, including bladder cancer. Most of the toxic compounds formed as a result of these infestations are derived either exogenously or formed endogenously and can be conjugated with glutathione (GSH) via glutathione S‐transferase (GST). The present study investigates the effect of Schistosma haematobium infection on the activity of GST and glutathione reductase (GR) and levels of glutathione and free radicals (measured as thiobarbituric acid reactive substances) in different organs of the male hamster. The total activity of GST was increased in several organs; in kidney by 50 and 46% at 6 and 10 weeks postinfection, respectively, and in bladder tissues by 169, 23, and 130% at 2, 4, and 6 weeks postinfection, respectively. In support of this, the expression of GST isozymes was also induced in kidney and bladder tissues at early stages (2, 4, and 6 weeks) and reduced at the later stages of infection (8 and 10 weeks). In contrast, the expression of these isozymes was decreased in the spleen and liver at 2, 4, 6, 8, and 10 weeks postinfection. Also, such activity was decreased in lungs by 74 and 78% and in bladders by 65 and 72% at 8 and 10 weeks postinfection, respectively. GSH levels increased in lungs by 95, 40, and 56% at 2, 4, and 6 weeks and in spleen by 26 and 74% at 4 and 6 weeks, respectively, but decreased at later stages of S. haematobium infection in these organs. The depletion of GSH levels also occurred in bladders by 72 and 54% at 8 and 10 weeks postinfection, respectively. The activity of GR was increased in the livers, lungs, and kidneys of the S. haematobium‐infected hamster. TBARS also increased in the lung by 14, 65, 53, 828, and 624% and in the kidney by 64, 29, 87, 190, and 111%, and in the bladder by 216, 23, 1468, 528, and 1025% at 2, 4, 6, 8, and 10 weeks postinfection, respectively. This study indicates that low GST expression and high levels of free radicals could provide new evidence for damage to the bladder and other organs as a result of S. haematobium infection. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:138–145, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10071
Effect of oral administration of arabic gum on cisplatin‐induced nephrotoxicity in rats
Authors: Al‐Majed Abdulhakeem A. , Abd‐Allah Adel R. A. , Al‐Rikabi Ammar C. , Al‐Shabanah Othman A. , Mostafa Adel M. 
Published: June 2003

AbstractIt has been recently postulated from our laboratory that Arabic gum (AG) offers a protective effect in the kidney of rats against nephrotoxicity induced by gentamicin via inhibiting lipid peroxidation. It has also recently shown a powerful antioxidant effect through scavenging superoxide anions. In this study we utilized a rat model of cisplatin (CP)‐induced nephrotoxicity to determine its peak time following (1, 2, 5, and 7 days) of a single CP (7.5 mg/kg, i.p.) injection. Also, a possible protective effect of cotreatment with AG (7.5 g/kg/day p.o.) on CP‐induced nephrotoxicity was investigated. Biochemical as well as histological assessments were carried out. CP‐induced nephrotoxicity was manifested by significant elevations of the functional parameters blood urea, serum creatinine, and kidney/body weight ratio. Maximum toxic effects of CP were observed 5 days after its injection, while it started after day 1 in the biochemical parameters, such as glutathione depletion in the kidney tissue with concomitant increases in lipid peroxides and platinum content. Additionally, severe necrosis and desquamation of tubular epithelial cells in renal cortex as well as interstitial nephritis were observed after 5 days in CP‐treated animals. Five days after AG cotreatment with CP did not protect the kidney from the damaging effects of CP. However, it significantly reduced CP‐induced lipid peroxidation. These findings suggest that lipid peroxidation is not the main cause of CP‐induced nephrotoxicity but it is rather more dependent on other factors such as platinum disposition in renal interstitial tubules. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:146–153, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10072
Voltage‐dependent ebselen and diorganochalcogenides inhibition of 45Ca2+ influx into brain synaptosomes
Authors: Moretto M. B. , Rossato J. I. , Nogueira C. W. , Zeni G. , Rocha J. B. T. 
Published: June 2003

AbstractBy mediating the Ca2+ influx, Ca2+ channels play a central role in neurotransmission. Chemical agents that potentially interfere with Ca2+ homeostasis are potential toxic agents. In the present investigation, changes in Ca2+ influx into synaptosomes by organic forms of selenium and tellurium were examined under nondepolarizing and depolarizing conditions induced by high KCl concentration (135 mM) or by 4‐aminopyridine (4‐AP). Under nondepolarizing conditions, ebselen (400 μM) increased Ca2+ influx; diphenyl ditelluride (40–400 μM) decreased Ca2+ in all concentrations tested; and diphenyl diselenide decreased Ca2+ influx at 40 and 100 μM, but had no effect at 400 μM. In the presence of KCl as depolarizing agent, ebselen and diphenyl ditelluride decreased Ca2+ influx in a linear fashion. In contrast, diphenyl diselenide did not modify Ca2+ influx into isolated nerve terminals. In the presence of 4‐AP (3 mM) as depolarizing agent, ebselen (400 μM) caused a significant increase, whereas diphenyl diselenide and diphenyl ditelluride inhibited Ca2+ influx into synaptosomes. The results can be explained by the fact that the mechanism through which 4‐AP and high K+ induced elevation of intracellular Ca2+ is not exactly coincident. The mechanism by which diphenyl ditelluride and ebselen interact with Ca2+ channel is unknown, but may be related to reactivity with critical sulfhydryl groups in the protein complex. The results of the present study indicate that the effects of organochalcogenides were rather complex depending on the condition and the depolarizing agent used. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:154–160, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10073
Relationship between expression of HSP70 and metallothionein and oxidative stress during mercury chloride induced acute liver injury in rats
Authors: Reus Isabel Sánchez , Bando Inmaculada , Andrés David , Cascales María 
Published: June 2003

AbstractMercury is a highly toxic metal which induces oxidative stress. Metallothionein and heat shock protein 70 (HSP70) are stress proteins involved in response to different stimuli. In the present study rats were administered per oral application by gavage, a single daily dose (0.1 mg/kg) of HgCl2 for 3 consecutive days. To find a relation between these two stress proteins and mercury, parameters of liver injury, redox state of the cells, and the expression and protein levels of HSP70 and metallothionein by Northern and Western blot analysis were assayed either in blood or in liver. HgCl2 at the doses of 0.1 mg/kg induced liver injury detected by a slight increase in serum aspartate aminotransferase and alkaline phosphatase activities and by the enhanced levels of bilirubin. Oxidative stress was detected by a significant decrease in protein–SH and an increase in thiobarbituric acid reactive substances in liver following one dose of mercury. mRNA and protein levels of both metallothionein and HSP70 increased progressively from first to third doses of mercury. We conclude that against low doses of mercury that produce a slight liver injury and oxidative stress, the liver rapidly responds by inducing the expression of metallothionein and HSP70. We suggest that metallothionein induction attenuates the decrease in protein–SH induced by the first dose of mercury, since metallothionein increases the pool of thiol groups in the cytosol eliminating oxygen radicals and inhibiting lipid peroxidation. From these results we can suggest that the changes observed in these stress proteins by the effect of mercury appear to be a response rapidly induced at transcriptional and at translational levels. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:161–168, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10074
Catalyzation of cocaine N‐demethylation by cytochromes P4502B, P4503A, and P4502D in fish liver
Authors: Arinç Emel , Bozcaarmutlu Azra 
Published: June 2003

AbstractCocaine N‐demethylation by microsomal cytochrome P450s is the principal pathway in cocaine bioactivation and hepatotoxicity. P450 isozymes involved in N‐demethylation of cocaine have not been elucidated yet and they differ from species to species. In humans and mice, P4503A contributes to cocaine N‐demethylase activity, whereas in rats, both P4503A and P4502B participate. In the present study, contribution of different P450 isozymes to cocaine N‐demethylase activity was studied in vitro with fish liver microsomes. The specific cocaine N‐demethylase activity was found to be 0.672 ± 0.22 nmol formaldehyde formed/min/mg protein (mean ± SD, n = 6). Cocaine N‐demethylase exhibited biphasic kinetics, and from the Lineweaver–Burk plot, two Km values were calculated as 0.085 and 0.205 mM for the high‐ and low‐affinity enzyme. These results indicate that N‐demethylation of cocaine in mullet liver microsomes is catalyzed by at least two cytochrome P450 isozymes. Inhibitory effects of cytochrome P450 isozyme‐selective chemical inhibitors, ketoconazole, cimetidine, SKF‐525A, and quinidine, on cocaine N‐demethylase activity were studied at 50, 100, and 500 μM concentrations of these inhibitors. At 100 μM final concentrations, ketoconazole (P4503A inhibitor), SKF‐525A (inhibitor of both P4502B and P4503A), and cimetidine (P4503A inhibitor) inhibited N‐demethylation activity by 73, 69, and 63%, respectively. Quinidine, P4502D‐specific inhibitor, at 100 μM final concentration, reduced N‐demethylation activity down to 64%. Aniline, a model substrate for P4502E1, did not alter N‐demethylase activity in the final concentration of 100 μM. IC50 values were calculated to be 20 μM for ketoconazole, 48 μM for cimetidine (both specific P4503A inhibitors), 164 μM for quinidine (P4502D inhibitor), and 59 μM for SKF‐525A (inhibitor of both P4503A and P4502B). The contribution of P4502B to cocaine N‐demethylase activity in mullet liver microsomes was further explored by the use of purified mullet cytochrome P4502B in the reconstituted system containing purified mullet P450 reductase and lipid. The turnover number was calculated as 4.2 nmol HCOH/(min nmol P450). Overall, these results show that P4503A and P4502B are the major P450s responsible for N‐demethylation of cocaine, whereas contribution of P4502D is a minor one, and P4502E1 is not involved in the N‐demethylation of cocaine in mullet liver microsomes. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:169–176, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10075
Prophylactic protection by N‐acetylcysteine against the pulmonary injury induced by 2‐chloroethyl ethyl sulfide, a mustard analogue
Authors: Das Salil K. , Mukherjee Shyamali , Smith Milton G. , Chatterjee Diptendu 
Published: June 2003

AbstractMustard gas exposure causes adult respiratory distress syndrome associated with lung injury. The purpose of this study was to investigate whether an antioxidant, such as N‐acetylcysteine (NAC), has any protective effect. Guinea pigs were given single exposure (0.5–6 mg/kg body weight) of 2‐chloroethyl ethyl sulfide (CEES) as a mustard analogue intratracheally and maintained for various lengths of time (1 h to 21 days). Within 1 h of CEES infusion at 4 mg/kg, high levels of tumor necrosis factor α (TNF‐α), ceramides, and nuclear factor κB accumulated in lung and alveolar macrophages. Both acid and neutral sphingomyelinases were activated within 4 h. These signal transduction events were associated with alteration in the oxygen defense system. Within 1 h of exposure to CEES (6 mg/kg body weight), there was 10‐fold increase in the 125I‐BSA leakage into lung tissue, indicating severe lung injury. Although low level of CEES exposure (0.5 mg/kg body weight) produced symptoms of chemical burn in lung as early as 1 h after exposure, the severity of edema, congestion, hemorrhage, and inflammation increased progressively with time (1 h to 21 days). Feeding of single dose of NAC (0.5 g) by gavage just before the CEES infusion was ineffective to counteract these effects. However, consumption of the antioxidant in drinking water for 3 or 30 days prior to CEES exposure significantly inhibited the induction of TNF‐α, activation of neutral and acid sphingomyelinases, production of ceramides, activation of caspases, leakage of 125I‐bovine serum albumin (125I‐BSA) into lung tissue, and histological alterations in lung. Pretreatment with NAC for 3 and 30 days protected against 69–76% of the acute lung injury. Therefore, NAC may be an antidote for CEES‐induced lung injury. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:177–184, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10076
Comparative effects of herbicide dicamba and related compound on plant mitochondrial bioenergetics
Authors: Peixoto Francisco , Vicente Joaquim A. F. , Madeira Vítor M. C. 
Published: June 2003

AbstractThe herbicide dicamba (3,6‐dichloro‐2‐methoxybenzoic acid) was evaluated for its effects on bioenergetic activities of potato tuber mitochondria to elucidate putative mechanisms of action and to compare its toxicity with 2‐chlorobenzoic acid. Dicamba (4 μmol/mg mitochondrial protein) induces a limited stimulation of state 4 respiration of ca. 10%, and the above concentrations significantly inhibit respiration, whereas 2‐chlorobenzoic acid maximally stimulates state 4 respiration (ca. 50%) at about 25 μmol/mg mitochondrial protein. As opposed to these limited effects on state 4 respiration, transmembrane electrical potential is strongly decreased by dicamba and 2‐chlorobenzoic acid. Dicamba (25 μmol/mg mitochondrial protein) collapses, almost completely, Δψ; similar concentrations of 2‐chlorobenzoic acid promote Δψ drops of about 50%. Proton permeabilization partially contributes to Δψ collapse since swelling in K‐acetate medium is stimulated, with dicamba promoting a stronger stimulation. The Δψ decrease induced by dicamba is not exclusively the result of a stimulation on the proton leak through the mitochondrial inner membrane, since there was no correspondence between the Δψ decrease and the change on the O2 consumption on state 4 respiration; on the contrary, for concentrations above 8 μmol/mg mitochondrial protein a strong inhibition was observed. Both compounds inhibit the activity of respiratory complexes II and III but complex IV is not significantly affected. Complex I seems to be sensitive to these xenobiotics. In conclusion, dicamba is a stronger mitochondrial respiratory chain inhibitor and uncoupler as compared to 2‐chlorobenzoic acid. Apparently, the differences in the lipophilicity are related to the different activities on mitochondrial bioenergetics. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:185–192, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10077
Effects of pycnogenol treatment on oxidative stress in streptozotocin‐induced diabetic rats
Authors: Maritim A. , Dene B. A. , Sanders R. A. , Watkins J. B. 
Published: June 2003

AbstractFree radicals and oxidative stress have been implicated in the etiology of diabetes and its complications. This in vivo study has examined whether subacute administration of pycnogenol, a French pine bark extract containing procyanidins that have strong antioxidant potential, alters biomarkers of oxidative stress in normal and diabetic rats. Diabetes was induced in female Sprague‐Dawley rats by a single injection of streptozotocin (90 mg/kg body weight, ip), resulting (after 30 days) in subnormal body weight, increased serum glucose concentrations, and an increase in liver weight, liver/body weight ratios, total and glycated hemoglobin, and serum aspartate aminotransferase activity. Normal and diabetic rats were treated with pycnogenol (10 mg/kg body weight/day, ip) for 14 days. Pycnogenol treatment significantly reduced blood glucose concentrations in diabetic rats. Biochemical markers for oxidative stress were assessed in the liver, kidney, and heart. Elevated hepatic catalase activity in diabetic rats was restored to normal levels after pycnogenol treatment. Additionally, diabetic rats treated with pycnogenol had significantly elevated levels of reduced glutathione and glutathione redox enzyme activities. The results demonstrate that pycnogenol alters intracellular antioxidant defense mechanisms in streptozotocin‐induced diabetic rats. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:193–199, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10078
Gene expression in rat skin induced by irritating chemicals
Authors: Rogers James V. , Garrett Carol M. , McDougal James N. 
Published: June 2003

AbstractOccupational skin disease is the second most significant cause of occupational disease, after accidents. Irritation from occupational chemicals such as solvents, hydrocarbons, and surfactants are one cause of this disease. Gene expression studies provide useful information about normal processes in the skin and responses of the skin to exogenous chemicals. We exposed rats, cutaneously, to sodium lauryl sulfate (SLS, 1% and 10% aqueous solution), m‐xylene (pure liquid), and d‐limonene (pure liquid) for 1 h and measured transcriptional responses at the end of the exposure and 3 h later for comparison with untreated skin samples. Total skin RNA was isolated and analyzed using the Affymetrix RatTox U34 array. Using the Affymetrix software, we found that 234 of approximately 850 genes were detected as present in at least 80% of the normal skin samples. The largest number of these genes was related to metabolism, oxidative/cellular stress, and signal transduction. Limonene caused the largest change in mRNA levels with a total of 34 increased transcripts and 4 decreased transcripts. Xylene treatment resulted in 6 increased transcripts and 14 decreased transcripts, while 10% SLS caused 5 transcripts to increase and 17 to decrease. Only two transcripts were observed to change in skin following a 1% SLS exposure. Sodium lauryl sulfate transcript changes increased with dose and were maximum at 4 h. Limonene transcript changes were more numerous at 1 h than at 4 h. The observed differences may reflect different mechanisms of irritation. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:123–137, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10079
Stochastic proximity embedding
Authors: Agrafiotis Dimitris K. 
Published: June 2003

AbstractWe introduce stochastic proximity embedding (SPE), a novel self‐organizing algorithm for producing meaningful underlying dimensions from proximity data. SPE attempts to generate low‐dimensional Euclidean embeddings that best preserve the similarities between a set of related observations. The method starts with an initial configuration, and iteratively refines it by repeatedly selecting pairs of objects at random, and adjusting their coordinates so that their distances on the map match more closely their respective proximities. The magnitude of these adjustments is controlled by a learning rate parameter, which decreases during the course of the simulation to avoid oscillatory behavior. Unlike classical multidimensional scaling (MDS) and nonlinear mapping (NLM), SPE scales linearly with respect to sample size, and can be applied to very large data sets that are intractable by conventional embedding procedures. The method is programmatically simple, robust, and convergent, and can be applied to a wide range of scientific problems involving exploratory data analysis and visualization. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 1215–1221, 2003
An algorithm to delineate and integrate topological basins in a three‐dimensional quantum mechanical density function
Authors: Malcolm Nathaniel O. J. , Popelier Paul L. A. 
Published: June 2003

AbstractThe growing activity in the area of Quantum Chemical Topology warrants a new algorithm to delineate topological basins in 3D scalar fields other than the electron density. A method based on the “octal tree search algorithm” of computer graphics is proposed to reach this goal. We illustrate the algorithm on the L(r) function, which is the negative of the Laplacian of the electron density. Because of its complicated topology, even in a simple test molecule such as water, it benefits from the octal tree algorithm as a robust, compact, and general technique to find the boundaries of topological basins. For the first time, we are able to compute the population and volume of the core and valence (bonding and nonbonding, i.e., lone pair) basins given by L(r)'s topology. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 1276–1282, 2003