Structure of 7,12-dimethylbenz(a)anthracene-guanosine adducts

Arene oxides have been proposed as the reactive intermediates in the process of carcinogenesis induced by polycyclic aromatic hydrocarbons. The present study defines the structures of four guanosine adducts formed by the reaction of 7,12-dimethylbenz[a]anthracene-5,6-oxide with polyguanylic acid. The modified polymer was hydrolyzed to nucleotides and the hydrophobic guanosine adducts separated from unmodified guanosine by LH-20 column chromatograhy. The adducts were further resolved into four components (I-IV) by reverse phase high pressure liquid chromatography. Analysis of the ultraviolet, circular dichroism, mass, and proton magnetic resonance spectra of these compounds, or their acetate and free base derivatives, indicates that in all four compounds the aromatic hydrocarbon is present on the 2 amino group of guanine. Compounds I and IV, and II and III constitute diastereoisomeric pairs, respectively. In the I and IV pair, the adducts result from addition at the 6 position of the original dimethylbenz[a]anthracene oxide, whereas in the II and III pair, the addition occurs at the 5 position. Indirect evidence suggests that trans opening of the oxide occurred in all cases but this remains to be established.     

Interactions of "ultra-low" doses of naltrexone and morphine in mature and young male and female rats

Sex and age influence morphine analgesia in humans and animals. Mature rats show greater morphine analgesia in males than in females. Ultra-low doses of naltrexone enhance morphine analgesia. In mature rats (18-22 weeks), naltrexone (0.002-2.0 mg/kg)-morphine (2 mg/kg) cotreatment enhanced morphine analgesia in females, an effect inversely related to naltrexone dose. Conversely, in mature male rats, naltrexone tended to decrease morphine analgesia with increasing dose. In young rats (8-10 weeks), morphine analgesia was unrelated to sex and in both sexes the naltrexone-morphine interaction was negligible. These data show that dose, age, and sex alter the naltrexone-morphine interaction in rats.     

Local error bounds for post‐processed finite element calculations

In this paper we produce tight guaranteed bounds for the error in the pointwise values of the derivatives of a post‐processed finite element solution to a potential flow problem, in which the boundary condition is purely normal velocity. Our approach has to be modified for the problems with Dirichlet boundary conditions. The aim is to produce a tight envelope of certainty within which the exact value is guaranteed to lie. Our numerical experiments produce narrow envelopes at interior points and at points close to or on the boundary. Copyright © 1999 John Wiley & Sons, Ltd.     

Intelligent tracking in manufacturing

Dynamic scheduling is an important new innovation in manufacturing and supply chain management. However, the success of dynamic scheduling will depend on real-time information. This paper describes intelligent tracking technologies that provide real-time information throughout the supply chain to support keywords a logistics planning and execution.     

Persistent organic pollutants in outmigrant juvenile chinook salmon from the Lower Columbia Estuary, USA

Although chemical contaminants are recognized as a potential factor contributing to the salmon declines in the Pacific Northwest, United States, information on contaminant concentrations in threatened and endangered salmon from the Columbia Estuary is limited. In this study we monitored exposure to several persistent organic pollutants [polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethanes (DDTs) and other organochlorine pesticides] in outmigrant juvenile fall chinook salmon (Oncorhynchus tschawytscha) in the Lower Columbia River, and evaluated the potential for adverse effects on salmon and the estuarine food web. Contaminants were measured in whole bodies and stomach contents of subyearling to yearling chinook collected in 2001 and 2002 from sites near the confluence of the Columbia and Willamette Rivers, Longview, and within the lower Estuary. The contaminants detected at highest concentrations in salmon whole bodies were PCBs and DDTs. Average concentrations of PCBs in salmon from the sampling sites ranged from 1300 to 14,000 ng/g lipid, in some cases exceeding the recently estimated threshold for adverse health effects in juvenile salmonids of 2400 ng/g lipid. Average DDT concentrations ranged from 1800 to 27,000 ng/g lipid. These levels are among the highest measured in juvenile salmon from Pacific Northwest estuaries to date. Concentrations of PCBs and DDTs in salmon whole bodies showed no clear spatial gradient from the Willamette/Columbia Confluence to the mouth of the Columbia, but tended to be higher in larger fish and older fish, suggesting a correlation with estuarine residence time. PCBs, DDTs, and PAHs were all found in salmon stomach contents, indicating that prey is a source of exposure. Hatchery feed may have contributed to contaminant body burdens in those fish that were of hatchery origin. Contaminant body burdens in salmon were poorly correlated with contaminant concentrations previously measured in local bed sediments, suggesting that pelagic as well as benthic sources are important in determining salmon exposure.     

Detection of occult low-grade b-cell non-Hodgkin's lymphoma in patients with chronic hepatitis C infection and mixed cryoglobulinemia

Hepatitis C virus (HCV) is both hepatotropic and lymphotropic and has been shown to be associated with the benign lymphoproliferative disorder, mixed cryoglobulinemia (MC). Preliminary studies suggest that there may be an association between chronic hepatitis C, MC, and non-Hodgkin's lymphoma (NHL). The aim of this study was to determine whether patients with chronic HCV and MC have occult bone marrow NHL. Sixteen patients with chronic HCV and clinically active MC underwent bone marrow biopsy and aspiration. Flow cytometry was performed looking for abnormal B-cell lineage. Molecular genetic studies were performed to identify B-cell monoclonality. Nine of 16 patients (56%) had abnormal marrow morphology, 7 (44%) were interpreted as suspicious for lymphoma, and 2 (13%) as consistent with lymphoma. Flow cytometry on 13 patients identified 5 (39%) with increased B-cell populations. Molecular analysis on 13 patients identified 3 (23%) with monoclonal proliferation of the B-cell lineage. All 13 patients tested for Epstein-Barr virus were negative by polymerase chain reaction (PCR). Four of 16 patients (25%) had marrow morphology and evidence of a monoclonal B-cell population by flow cytometry and/or molecular studies, consistent with B-cell NHL. These findings confirm the presence of lymphoproliferative disorders in patients with chronic HCV and MC. Some of these disorders meet the morphological and molecular criteria for the diagnosis of malignant lymphoma.     

Effects of hemodialyzer reuse on clearances of urea and beta2-microglobulin. The Hemodialysis (HEMO) Study Group

Thalamic innervation plays a major role in parcellation of neocortex and maturation of cortical circuits. While the underlying mechanisms are unknown, lesion studies have identified GABAA receptors in neocortex as molecular targets of thalamic regulation [J. Paysan, A. Kossel, J. Bolz, J.M. Fritschy, Area-specific regulation of gamma-aminobutyric acid A receptor subtypes by thalamic afferents in developing rat neocortex, Proc. Natl. Acad. Sci. USA 94 (1997) 6995-7000]. To determine the factors regulating the expression of GABAA receptors, the overall level of neuronal activity was chronically modulated in neonatal rat cortex. Slices of Elvax polymer loaded with the N-methyl-D-asparate (NMDA) receptor antagonist MK-801 or with brain derived neurotrophic factor (BDNF) were placed unilaterally over the left parietal cortex in newborn animals. Unlike thalamic lesions (Paysan et al., 1997), these chronic drug treatments did not alter the laminar distribution or the expression level of the four major GABAA receptor alpha subunit isoforms (alpha 1, alpha 2, alpha 3, alpha 5) in primary somatosensory cortex (S1), as assessed immunohistochemically after one week. In particular, the staining of the barrel field in layers III-IV, which is very prominent with the alpha 1-subunit, was preserved in the drug-treated hemisphere. Even systemic administration of MK-801 at birth, which resulted in pronounced retardation of cortical development, had no effect on the laminar distribution and staining intensity of the four GABAA receptor alpha subunit variants. However, the size of barrels in S1, as measured in tangential sections stained for the GABAA receptor alpha 1 subunit, was enlarged upon chronic, topical blockade of NMDA receptors with MK-801 and was reduced to the same extent upon chronic exposure to BDNF. Thus, these pharmacological treatments modulated cortical growth, possibly by exerting opposite effects on neuronal activity in S1. The results suggest that the parcellation of somatosensory cortex and the laminar distribution of GABAA receptor subtypes are governed primarily by factors independent of thalamocortical activity.     

Recovery of fMRI activation in motion area MT following storage of the motion aftereffect

We used functional magnetic resonance imaging (fMRI) during storage of the motion aftereffect (MAE) to examine the relationship between motion perception and neural activity in the human cortical motion complex MT+ (including area MT and adjacent motion-selective cortex). MT+ responds not only to physical motion but also to illusory motion, as in the MAE when subjects who have adapted to continuous motion report that a subsequent stationary test stimulus appears to move in the opposite direction. In the phenomenon of storage, the total decay time of the MAE is extended by inserting a dark period between adaptation and test phases. That is, when the static test pattern is presented after a storage period equal in duration to the normal MAE, the illusory motion reappears for almost as long as the original effect despite the delay. We examined fMRI activation in MT+ during and after storage. Seven subjects viewed continuous motion, followed either by an undelayed stationary test (immediate MAE) or by a completely dark storage interval preceding the test (stored MAE). Like the perceptual effect, activity in MT+ dropped during the storage interval then rebounded to reach a level much higher than after the same delay without storage. Although MT+ activity was slightly enhanced during the storage period following adaptation to continuous motion (compared with a control sequence in which the adaptation grating oscillated and no MAE was perceived), this enhancement was much less than that observed during the perceptual phenomenon. These results indicate that following adaptation, activity in MT+ is pronounced only with the presentation of an appropriate visual stimulus, during which the MAE is perceived.