bluuebunny/crossref_metadata_2025 huggingface dataset:
Where did the ventricular localization of mental faculties come from?
Authors: Green Christopher D.
Published: April 2003

During the Middle Ages it was widely believed that the various mental faculties—sensation, cognition, memory, and so forth—were each located in a specific part of the three ventricles that were thought to be housed in the brain. The origin of this scheme was commonly attributed to the ancient scholars, but it was rare for a specific individual to be identified as the originator. Modern researchers sometimes attribute it to Galen, but Galen was clear in his contention that the mental faculties were located in the substance of the brain rather than in the ventricles. It was only later scholars who, using Galen's anatomy as their basis, placed the mental faculties in the ventricles themselves. The system came together piece by piece over a period of centuries, probably not appearing fully in the form known to the Medieval world until the Middle Ages themselves. This article traces the development of the theory of ventricular localization of the mental faculties from the Ancient world to the early part of the Middle Ages. © 2003 Wiley Periodicals, Inc.
Comparison of the three‐dimensional structures of a human Bence‐Jones dimer crystallized on Earth and aboard US Space Shuttle Mission STS‐95
Authors: Terzyan Simon S. , Bourne Christina R. , Ramsland Paul A. , Bourne Philip C. , Edmundson Allen B.
Published: April 2003

Crystals of a human (Sea) Bence‐Jones dimer were produced in a capillary by vapor diffusion under microgravity conditions in the 9 day US Space Shuttle Mission STS‐95. In comparison to ground‐based experiments, nucleation was facile and spontaneous in space. Appearance of a very large (8 × 1.6 × 1.0 mm) crystal in a short time period is a strong endorsement for the use of microgravity to produce crystals sufficiently large for neutron diffraction studies. The Sea dimer crystallized in the orthorhombic space group P212121, with a = 48.9 Å, b = 85.2 Å, and c = 114.0 Å. The crystals grown in microgravity exhibited significantly lower mosaicities than those of ground‐based crystals and the X‐ray diffraction data had a lower overall B factor. Three‐dimensional structures determined by X‐ray analysis at two temperatures (100 and 293 K) were indistinguishable from those obtained from ground‐based crystals. However, both the crystallographic R factor and the free R factor were slightly lower in the models derived from crystals produced in microgravity. The major difference between the two crystal growth systems is a lack of convection and sedimentation in a microgravity environment. This environment resulted in the growth of much larger, higher‐quality crystals of the Sea Bence‐Jones protein. Structurally, heretofore unrecognized grooves on the external surfaces of the Sea and other immunoglobulin‐derived fragments are regular features and may offer supplementary binding regions for super antigens and other elongated ligands in the bloodstream and perivascular tissues. Copyright © 2003 John Wiley & Sons, Ltd.
Using a 1 M Gd‐chelate (gadobutrol) for total‐body three‐dimensional MR angiography: Preliminary experience
Authors: Goyen Mathias , Herborn Christoph U. , Vogt Florian M. , Kröger Knut , Verhagen Rüdiger , Yang Fan , Bosk Silke , Debatin Jörg F. , Ruehm Stefan G.
Published: April 2003

Purpose

To determine whether higher concentrated gadolinium chelates are advantageous for the recently introduced concept of total‐body magnetic resonance angiography (MRA), allowing whole‐body coverage, extending from the carotid arteries to the runoff vessels, in merely 72 seconds.

Materials and Methods

Total‐body three‐dimensional (3D) MRA using a 1 M Gd‐chelate (gadobutrol, Gadovist®, Schering, Berlin, Germany) at a dosage of 0.2 mmol/kg body‐weight (biphasic injection protocol: 1.3 mL/second and 0.7 mL/second) was performed on three healthy volunteers and ten consecutive patients with DSA‐documented peripheral vascular disease. Separated by at least 72 hours, the three healthy volunteers also underwent the same MRA‐protocol, using gadopentetate dimeglumine in equimolar dosages.

Results

Compared to equimolar dosages, mean signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio (CNR) values in the three volunteers were significantly higher (up to 32.5% for the arteries of the thighs and calves) using gadobutrol. In the ten patients, gadobutrol‐based total‐body MRA accurately assessed significant stenoses (luminal narrowing > 50%) with sensitivities and specificities of 96.2% (95% CI 0.83–0.97) and 95.7% (95% CI 0.84–0.96), respectively, compared to digital subtraction angiography.

Conclusion

The MRA image quality for total‐body MRA provided by the administration of gadobutrol is superior to that obtained following administration of an identical dose of gadopentetate dimeglumine, and therefore shows promise for use as a comprehensive single exam assessing the entire arterial system for the presence of atherosclerotic disease manifestations. J. Magn. Reson. Imaging 2003;17:565–571. © 2003 Wiley‐Liss, Inc.
Räumliche Variabilität der Phosphorgehalte im Oberboden landwirtschaftlich genutzter Flächen in kleinen Einzugsgebieten
Authors: Halbfaß Stefan , Grunewald Karsten
Published: April 2003

In den Oberböden zweier kleiner landwirtschaftlich genutzter Einzugsgebiete wurde die räumliche Variabilität der Gehalte an Gesamtphosphor (Pt) in Abhängigkeit von der Reliefposition und der Nutzung untersucht. Bei mittleren Pt‐Gehalten von 982 mg kg–1 lagen 80 % der Werte zwischen 560 und 1530 mg kg–1. Die jeweils höchsten Gehalte wurden auf der Hangkuppe und am Hangfuß gefunden, hingegen an den Mittelhängen stets niedrigere Gehalte. Auf den Hangpositionen wurde die räumliche Variabilität durch die Relief‐ und Bodeneigenschaften verursacht, auf dem Maßstab der Einzugsgebiete vor allem durch die Bewirtschaftungsmethoden. Diese Unterschiede müssen für die Modellierung des diffusen P‐Eintrages in die Oberflächengewässer berücksichtigt werden.
Adsorption of “real” dissolved organic matter on the clay and fine silt fractions of a forested Stagnic Gleysol
Authors: Rennert Thilo , Mansfeldt Tim
Published: April 2003

Dissolved organic matter (DOM) in soils is partially adsorbed when passing through a soil profile. In most adsorption studies, water soluble organic matter extracted by water or dilute salt solutions is used instead of real DOM gained in situ by lysimeters or ceramic suction cups. We investigated the adsorption of DOM gained in situ from three compartments (forest floor leachate and soil solution from 20 cm (Bg horizon) and 60 cm depth (2Bg horizon)) on the corresponding clay and fine silt fractions (< 6.3 μm, separated together from the bulk soil) of the horizons Ah, Bg, and 2Bg of a forested Stagnic Gleysol by batch experiments. An aliquot of each clay and fine silt fraction was treated with H2O2 to destroy soil organic matter. Before and after the experiments, the solutions were characterized by ultra‐violet and fluorescence spectroscopy and analyzed for sulfate, chloride, nitrate, and fluoride. The highest affinity for DOM was found for the Ah samples, and the affinity decreased in the sequence Ah > Bg > 2Bg. Dissolved organic matter in the 2Bg horizon can be regarded as slightly reactive, because adsorption was low. Desorption of DOM from the subsoil samples was reflected more realistically with a non‐linear regression approach than with initial mass isotherms. The results show that the extent of DOM adsorption especially in subsoils is controlled by the composition and by the origin of the DOM used as adsorptive rather than by the mineralogical composition of the soil or by contents of soil organic matter. We recommend to use DOM gained in situ when investigating the fate of DOM in subsoils.
Soil carbon and nitrogen response to 25 annual cattle manure applications
Authors: Hao Xiying , Chang Chi , Travis Greg R. , Zhang Fengrong
Published: April 2003

Improving manure management to benefit both agricultural production and the environment requires a thorough understanding of the long‐term effects of applied manure on soil properties. This paper examines the effect of 25 annual solid cattle manure applications on soil organic carbon (OC), total N (TN), and KCl‐extractable NO3‐N and NH4‐N under both non‐irrigated and irrigated conditions. After 25 annual manure applications, OC and TN contents increased significantly with the rate of manure application at the top two sampling depths (0–15 cm and 15–30 cm), and the increases were not affected by the irrigation treatment. The NO3 content increased at all sampling depths with greater increases observed under non‐irrigated conditions, while NH4 content was not affected by manure application rates or the irrigation treatment. The changes in OC and TN at the surface (0–15 cm) and 15–30 cm depth were dependent on the cumulative weight of manure added over the years. The relationships between cumulative manure OC added and soil OC content and between cumulative manure TN added and soil TN content were linear and not affected by the irrigation treatment. For every ton of manure OC added, soil OC increased by 0.181 g kg–1 in the topsoil (0–15 cm). Similarly, for every ton of manure TN added, surface soil TN increased by 0.192 g kg–1. The linear relationship between manure C added and soil C content suggests that the soil had a high capacity for short‐term C sequestration. However, the total amount of NO3‐N in the soil profile (0–150 cm) was affected by both the manure application rates and the irrigation treatment. A large amount of NO3 accumulated in the soil, especially under non‐irrigated conditions. The extremely high level of NO3 in the soil increases the potential risk of surface and groundwater pollution and losses to atmosphere as N2O.
Stellungnahme der Deutschen Bodenkundlichen Gesellschaft zum Konzept des BMVEL und BMU „Gute Qualität und sichere Erträge”︁
Authors: Laves Detlev , Gäth Stefan
Published: April 2003

No translation.
The transfer matrix method applied to steel sheet pile walls
Authors: Kort D. A.
Published: April 2003

This paper proposes two subgrade reaction models for the analysis of steel sheet pile walls based on the transfer matrix method. In the first model a plastic hinge is generated when the maximum moment in the retaining structure is exceeded. The second model deals with a beam with an asymmetrical cross‐section that can bend in two directions.

In the first part of this paper the transfer matrix method is explained on the basis of a simple example. Further the development of two computer models is described: Plaswall and Skewwall.

The second part of this paper deals with an application of both models. In the application of Plaswall the effect of four current earth pressure theories to the subgrade reaction method is compared to a finite element calculation. It is shown that the earth pressure theory is of major importance on the calculation result of a sheet pile wall both with and without a plastic hinge.

In the application of Skewwall the effectiveness of structural measures to reduce oblique bending is investigated. The results are compared to a 3D finite element calculation. It is shown that with simple structural measures the loss of structural resistance due to oblique bending can be reduced. Copyright © 2003 John Wiley & Sons, Ltd.
Interferon‐beta treatment in multiple sclerosis patients decreases the number of monocytes in peripheral blood
Authors: Anlar Omer , Tombul Temel , Ozbek Hanefi , Dilek Imdat
Published: April 2003

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, characterized by the presence of sclerotic lesions throughout the brain. During clinical activity, monocytes activation markers such as Interleukin 1 and tumor necrosis factor‐alpha (TNF‐α) increase. The effect of interferon beta (IFN‐β) in reducing exacerbation rate and in slowing sustained worsening of disability has been shown in MS. The aim of this study was to determine levels of monocytes percentage in peripheral blood of MS patients receiving IFN‐β.

We carried out this study in two groups of MS patients and a group of healthy subjects. First (study) group consisted of 13 patients treated by INF‐β. The control groups consisted of a) 14 MS patients group with no treatment by INF‐β and b) 20 healthy subjects. We counted the percentage of monocytes in the study group before and after one year of treatment by IFN‐β and in the control groups patients in the same period. At the end of one year, there was a significant reduction in the percentage of monocytes in peripheral blood of MS patients treated by interferon.
The effect of long‐term therapy with sodium valproate on oxidant/antioxidant status in epileptic children
Authors: Ozerol Elif , Aslan Mehmet , Cakmak Ecir Ali , Gulec Mukaddes , Yakinci Cengiz , Akyol Omer
Published: April 2003

Antiepileptic drugs may cause the changes in the oxidant/antioxidant status of the body. Reactive oxygen species have been suggested to be an important factor in the pathogenesis of various diseaases as well as drug interactions and/or adverse effects. The aim of this study, therefore, is to investigate the status of major antioxidant enzyme activities as well as the end products of lipid peroxidation in erythrocyte and plasma from epileptic children after therapy with sodium valproate (VPA). Superoxide dismutase (SOD), catalase (CAT) activities and malondialdehyde (MDA) levels in erythrocyte and plasma were analyzed in 41 epileptic patients under long‐term antiepileptic therapy with VPA and 32 healthy controls. Erythrocyte SOD activity was found to be increased (p=0.024) whereas erythrocyte CAT activity decreased (p=0.016) in patients with epilepsy under VPA treatment compared to the controls. MDA levels in erythrocyte were found to be markedly decreased in epileptic children compared to controls (p<0.001). In conclusion, decreased CAT activity seems to be compensated with increased SOD activity in erythrocytes protecting erythrocyte membranes from lipid peroxidation in patients with epilepsy under VPA treatment.
Polaron cyclotron resonance in II–VI compounds at high magnetic fields
Authors: Miura N. , Imanaka Y.
Published: April 2003

In this paper, we discuss the cyclotron resonance in II–VI compounds in very high magnetic fields, in particular, those in CdS where many different anomalies were observed in high magnetic fields. High magnetic fields enable us to observe clean cyclotron resonance spectra even in low mobility crystals, thus in most II–VI semiconductors we can study the polaron effect up to the high energy range well above the LO phonon energy. Resonant polaron effect is observed prominently and we can estimate the electron–phonon coupling strength from the magnitude of the anticrossing effect. In addition to the resonant polaron interaction, it was found that cyclotron effective mass shows a peculiar temperature dependence which is explained theoretically by the combination of the electron‐phonon interaction and the impurity scattering.
Estimation of infection and recovery rates for highly polymorphic parasites when detectability is imperfect, using hidden Markov models
Authors: Smith Tom , Vounatsou Penelope
Published: April 2003

A Bayesian hierarchical model is proposed for estimating parasitic infection dynamics for highly polymorphic parasites when detectability of the parasite using standard tests is imperfect. The parasite dynamics are modelled as a non‐homogeneous hidden two‐state Markov process, where the observed process is the detection or failure to detect a parasitic genotype. This is assumed to be conditionally independent given the hidden process, that is, the underlying true presence of the parasite, which evolves according to a first‐order Markov chain. The model allows the transition probabilities of the hidden states as well as the detectability parameter of the test to depend on a number of covariates. Full Bayesian inference is implemented using Markov chain Monte Carlo simulation. The model is applied to a panel data set of malaria genotype data from a randomized controlled trial of bed nets in Tanzanian children aged 6‐30 months, with the age of the host and bed net use as covariates. This analysis confirmed that the duration of infections with parasites belonging to the MSP‐2 FC27 allelic family increased with age. Copyright © 2003 John Wiley & Sons, Ltd.
Ontogenetic development of glutamate and GABA metabolizing enzymes in cultured cerebral cortex interneurons and in cerebral cortex in vivo
Authors: Larsson O. M. , Drejer J. , Kvamme E. , Svenneby G. , Hertz L. , Schousboe A.
Published: April 2003

The development of the enzymes phosphate activated glutaminase (PAG), glutamate dehydrogenase (GLDH), glutamic‐oxaloacetic‐transaminase (GOT), glutamine synthetase (GS), GABA‐transaminase (GABA‐T) and ornithine‐δ‐aminotransferase (Orn‐T) was followed in mouse cerebral cortex in vivo and in cultured mouse cerebral cortex interneurons. It was found that GLDH, GOT and Orn‐T exhibited an enhanced developmental pattern in the cultured neurons compared to cerebral cortex. The activities of PAG and GABA‐T developed in parallel in vivo and in culture but the activity of GS remained low in the cultured neurons compared to the increasing activity of this enzyme found in vivo. Compared to cerebral cortex the cultured neurons exhibited higher activities of PAG, GLDH and Orn‐T, whereas the activities of GABA‐T and GOT were lower in the cultured cells. The activity of GS in the cultured neurons was only 5–10% of the activity in cerebral cortex in vivo. It is concluded that neurons from cerebral cortex represent a reliable model system by which the metabolism and function of GABAergic neurons can be conveniently studied in a physiologically meaningful way.
Increased levels of UV‐induced protease activity in human UVAP‐1 cells exposed to gravity‐changing stress: involvement of E‐64‐sensitive proteases in suppression of UV mutagenicity
Authors: Takahashi Shunji , Zhang Hong‐Chang , Hasegawa Ritsuko , Karata Kiyonobu , Kita Kazuko , Wano Chieko , Yamaguchi Yoshitaka , Sugaya Shigeru , Nomura Jun , Ichinose Masaharu , Suzuki Nobuo
Published: April 2003

Under the 1 G condition, the increase in antipain‐sensitive protease activity promptly after UV (mainly 254 nm wavelength) irradiation in cultured human cells is detected and found to be one of the intriguing events involved in suppression of cell mutability. It was found that two cell lines, RSa and its variant UVAP‐1 cells are applicable; the former is hypermutable and not susceptible to protease activation, while the latter is hypomutable and susceptible. In the present study it was investigated whether the increase in protease activity by UV irradiation is also observed in hypomutable human UVAP‐1 cells exposed to gravity‐changing stress and whether the increase is involved in suppression of UV mutagenicity. Exposure of human UVAP‐1 cells to gravity‐changing stress such as free‐fall and parabolic flight prior to UV irradiation resulted in a pronounced increase in protease activity, but not to hypergravity conditions (2 and 10 G) prior to UV irradiation. To characterize the proteases, components of lysates from the cells exposed to free‐fall prior to UV irradiation were fractionated by high performance liquid chromatography, indicating two separate fractions with highly increased levels of E‐64‐sensitive protease activity. In the cells treated with E‐64 during their exposure to free‐fall, K‐ras codon 12 base substitution mutation was detected after UV irradiation, although the mutation was not detected after UV irradiation alone. Thus, the increase in E‐64‐sensitive protease activity may be involved in the suppression of UV mutagenicity in UVAP‐1 cells exposed to free‐fall.
Is MELD really the definitive score for liver allocation?
Authors: Lladó Laura , Figueras Juan , Memba Roberto , Xiol Xavier , Baliellas Carmen , Vázquez Santiago , Ramos Emilio , Torras Jaume , Rafecas Antoni , Fabregat Juan , Lama Carmen , Jaurrieta Eduardo
Published: April 2003

The best system for organ allocation is still a controversial issue. The aim of this study was to study the accuracy of four different scores to predict mortality on the waiting list and, thus, their usefulness to determine organ allocation. We retrospectively compared two groups of patients, those who died on waiting list (group D) and those who successfully underwent transplantation (group T) during the same time period. Four scores, at the time of entering the waiting list and just before liver transplantation or death, were evaluated. The evaluated scores were as follows: (1) the Child-Pugh classification; (2) the Model for End-Stage Liver Disease (MELD) score; (3) the Freeman scale; and (4) the Guardiola et al index. The mortality rate on waiting list was 15.9%. All studied scores, except Freeman scale, were higher in group D at the time of entrance on waiting list (MELD, 17.4 ± 8 v 12.3 ± 6, P = .02; Child, 9.9 ± 2 v 7.7 ± 2, P = .002; Freeman, 9.7 ± 4 v 7.3 ± 3.9, P = .09; Guardiola, 2.6 ± 0.9 v 1.7 ± 0.7, P = .001). C-statistics of all scores were similar and in all cases lower than 0.8 (MELD, 0.75; Child, 0.78; Freeman, 0.65; Guardiola, 0.79). None of the studied scores have an excellent accuracy to predict prognosis of patients on waiting list, mainly in case of populations with high proportion of hepatocellular carcinoma. Although the MELD score is rapidly available, standardized, and objective, it does not reflect the severity of patients with cancer or metabolic disorders.
The interaction between antiretroviral agents and tacrolimus in liver and kidney transplant patients
Authors: Jain Ashok Kumar B. , Venkataramanan Raman , Shapiro Ron , Scantlebury Velma P. , Potdar Santosh , Bonham Andrew C. , Ragni Margaret , Fung John J.
Published: April 2003

Solid organ transplantations have been performed successfully in selected HIV-positive patients with highly active antiretrovirus therapy (HAART). However, some of the medications in the HAART regimen require metabolism via the cytochrome P4503A, the same enzyme complex responsible for clearance of the calcineurin inhibitors cyclosporine and tacrolimus. Several case reports have described significant interactions between the agents used in HAART and immunosuppressive drugs. The goal of this report is to examine the extent of potential drug interactions between antiretroviral agents and tacrolimus after liver and kidney transplantation. Seven liver transplant (LTx) patients (M = 6, F = 1) and four kidney transplant (KTx) patients (M = 4) infected with HIV underwent surgery between September 1997 and January 2001. Initial immunosuppression consisted of tacrolimus and steroids for LTx patients or tacrolimus, steroids, and mycophenolate mofetil for KTx recipients. Their current baseline immunosuppression and HAART regimen were examined retrospectively. Of the seven liver recipients, one (case 4) died 2 weeks after LTx and never received HAART therapy posttransplantation. The remaining six patients were placed on a regimen consisting of two nucleoside reverse transcriptase inhibitors (NRTI) and one protease inhibitor (PI) (nelfinavir in 5, indinavir in 1) based on known viral sensitivities or history of a previous clinical response. Kidney recipients received NRTI and nonnucleoside reverse transcriptase inhibitors (NNRTI). The mean dose of tacrolimus in liver recipients was 0.6 mg/d, with mean trough concentration of 9.7 mg/mL. Compared with historic controls (liver transplant patients not on HAART), the average tacrolimus dose was 16-fold lower in patients on HAART. In contrast to liver recipients, HIV-positive kidney recipients not on PI therapy required a mean tacrolimus dose of 9.5 mg/d to maintain a mean trough concentration of 9.6 ng/mL. Of the two protease inhibitors used, nelfinavir seems to have a more profound effect than indinavir. When patients on nelfinavir alone (n = 5) were compared with a control group not on antiretroviral therapy, the need for a tacrolimus dose was 38 times lower (mean dose, 0.26 mg/d). Profound drug interactions between PI and tacrolimus have been observed requiring up to 50-fold reductions in dosage. This effect seems to be most pronounced with the use of nelfinavir as opposed to indinavir, although further experience is required to confirm this observation. In contrast, HAART using NRTI and NNRTI without the use of PI, as shown in kidney recipients, produces less significant effects on tacrolimus metabolism. Great caution and frequent drug level monitoring are necessary when HAART is introduced or withdrawn in HIV-positive recipients of organ transplants.
Engraftment assessment in human and mouse liver tissue after sex-mismatched liver cell transplantation by real-time quantitative PCR for Y chromosome sequences
Authors: Wang Ling-Jia , Chen Yong Ming , George David , Smets Francois , Sokal Etienne M. , Bremer Eric G. , Soriano Humberto E.
Published: April 2003

Transplanted hepatocytes can engraft, proliferate, and function permanently in host animals. After one cell infusion, however, engrafted hepatocytes constitute only between 1 in 200 to 1 in 3000 host liver cells. Although transplanted cells can be identified using biochemical and molecular techniques, more accurate methods are needed to evaluate interventions that could improve cell engraftment rates. Real-time polymerase chain reaction (PCR) was done using primers and probes complementary to human testis determining gene (SRY) and mouse testis-specific Y-encoded protein (TSPY) pseudogene. Tissue samples from human or mouse recipients of liver cell transplantation were used to determine the test ability to detect transplanted cell DNA. Real-time PCR for the human SRY and mouse TSPY were species- and sex-specific. These two tests were sensitive in the detection of male DNA. Test sensitivity was consistently found at minimum 1:10,000 of male and female DNA mixing curve in both human SRY and mouse TSPY assays. The optimal amount of sample DNA per reaction to produce the highest sensitivity was 300 ng to 1 μg. Real-time PCR gave similar results whether standard male-female mixtures were prepared from liver cells or mononuclear cells. Engraftment of male liver cells in female liver tissues in mice and humans ranging from 0.125% to 0.257% was successfully measured using this method. Real-time PCR for SRY and TSPY affords a specific, sensitive, and reproducible tool for chimerism analysis in transplanted human and mouse liver tissues. This method could be used to optimize current models of cell transplantation.
Nelfinavir, a protease inhibitor, increases sirolimus levels in a liver transplantation patient: A case report
Authors: Jain Ashok Kumar B. , Venkataramanan Raman , Fridell Jonathan A. , Gadomski Mary , Shaw Leslie M. , Ragni Margaret , Korecka Magdalena , Fung John
Published: April 2003

With the increasing success of liver transplantation and the proven effectiveness of highly active retroviral therapy in HIV-positive patients, liver transplantation has been performed successfully in selected HIV-positive recipients with CD4 and an HIV viral load response to highly active antiretroviral therapy. In these patients, an interaction between a protease inhibitor (nelfinavir) and tacrolimus has been shown. The effect of nelfinavir on the pharmacokinetics of sirolimus, a newer immunosuppressive drug, is currently not known. The goal of the present case report is to document the interaction between sirolimus and nelfinavir in a liver transplantation patient. A 40-year-old woman who was HIV positive underwent a cadaveric liver transplantation for acute fulminant liver failure secondary to nevirapine (a nonnucleoside reverse transcriptase inhibitor). Postoperatively, she was treated with tacrolimus and steroids. She experienced steroid-resistant rejection and was started on sirolimus on the 17th postoperative day. Kinetic parameters were determined after a 2-mg oral dose of sirolimus and 250 mg of nelfinavir by collecting multiple peripheral venous blood samples before and after sirolimus administration. The kinetic parameters were compared with parameters from three liver transplantation patients on sirolimus who were not on nelfinavir. After normalizing the kinetic parameters to sirolimus dose of 1 mg/d, 0-hour and 24-hour trough sirolimus concentrations were nine-fold and five-fold higher for the patient who was on nelfinavir, compared with those who were not on nelfinavir. The maximum concentration was 3.2 times higher, the area under the concentration curve was 1.6 times higher, and the terminal disposition half-life was prolonged by 60%. The time to reach the peak concentration was 1 hour in all patients. Increase in trough concentration, peak concentration area under the curve concentration, and prolongation of half-life of sirolimus has been shown in a patient who was on a low dose (one fifth the recommended dose) of nelfinavir.
Preservation of mouse liver tissue during cold storage in experimental solutions assessed by x-ray microanalysis
Authors: Kozlova Inna , Khalid Younis , Roomans Godfried M.
Published: April 2003

The increasing use of organs for transplantation necessitates the development of optimal preservation techniques. The goal of this study was to investigate changes in elemental content in mouse liver cells during cold storage by x-ray microanalysis in parallel with morphologic studies. Tissue was stored at 4°C for 4 to 12 hours in normal Krebs-Ringer solution (high sodium/potassium ratio), modified Krebs-Ringer solution (low Na+/K+ ratio), Euro-Collins solution, University of Wisconsin (UW) solution, or seven modified versions of the UW solution. Incubation of liver in normal Krebs-Ringer solution caused a significant increase in sodium and decrease in potassium concentrations in contrast to incubation in other solutions. The concentration of sodium, potassium, and chlorine in the cells closely followed the concentration in the storage solution, indicating that the intracellular concentration of these ions during storage is entirely dependent on diffusion processes. The calcium concentration was independent of the storage solution used. Studies by light and transmission electron microscopy showed good preservation of hepatocytes after storage for 8 and 12 hours in UW solution and its variants, modified Krebs-Ringer solution and Euro-Collins solution, but showed moderate damage to mitochondria and swelling of the endoplasmic reticulum in normal Krebs-Ringer solution. In addition, damage to the sinusoidal endothelial cells was observed after 4 hours in normal Krebs-Ringer solution and after 8 to 12 hours in the other solutions. In conclusion, the only factor determining the intracellular concentration of diffusible ions after cold tissue storage is the ionic composition of the extracellular medium. X-ray microanalysis provides an objective method for assessing whether the intracellular ionic composition of tissue is maintained during storage.
Serum phosphorus levels predict clinical outcome in fulminant hepatic failure
Authors: Chung Phillip Y. , Sitrin Michael D. , Te Helen S.
Published: April 2003

The aim of this pilot study was to evaluate the incidence of hypophosphatemia and its association with clinical outcome in fulminant hepatic failure (FHF). Patients with FHF referred for orthotopic liver transplantation (OLT) between January, 1991 and May, 2002 were identified. FHF was defined as the development of coagulopathy and encephalopathy within 8 weeks of onset of jaundice. Demographic and laboratory data, including serum phosphate, calcium, magnesium, creatinine, and PT/INR were obtained from medical records. Clinical outcomes (death, OLT, or hepatic recovery) and associated morbidities (renal failure, bleeding, and sepsis) also were noted. Thirty-eight patients, 8 men and 30 women, aged 34 ± 4 years, were included in the study. Hypophosphatemia (< 2.5 mg/dL) developed in 33 of 38 (87%) patients within 10 days of referral. Twelve patients (32%) died, 14 patients (37%) underwent OLT, and 12 patients (32%) recovered. The mean nadir serum phosphorus level was significantly lower in those who recovered compared with those who either died or required OLT (1.18 ± 0.54 versus 1.79 ± 1.00 mg/dL; P = .02). A trend toward lower mean serum phosphorus level also was noted in those who recovered compared with those who died (1.18 ± 0.54 versus 1.96 ± 1.35 mg/dL; P = .09). Serum phosphorus levels > 2.5 mg/dL was a predictor of mortality, and when used alone, was equivalent to the King’s College Criteria. In conclusion, hypophosphatemia occurred frequently in patients with FHF. Lower serum phosphorus levels were observed in patients who recovered as compared with those who died or required OLT, and may be associated with recovery of hepatic function. The greater decline in serum phosphorus level in those who recover hepatic function may represent cellular use of phosphorus during hepatocyte regeneration.
Molecular characterization of whitefly, Bemisia tabaci (Hemiptera: Aleyrodidae) populations infesting cassava
Authors: Abdullahi I. , Winter S. , Atiri G.I. , Thottappilly G.
Published: April 2003

Bemisia tabaci (Gennadius) populations, collected from cassava and other plants in major cassava-cultivation areas of Sub-saharan Africa and from elsewhere around the world, were studied to determine their biotype status and genetic variation. Random amplified polymorphic DNA–polymerase chain reaction (RAPD–PCR) markers were used to examine the genetic structure of the populations. The dendogram obtained using the neighbour joining method (NJ) split the cassava-associated populations from the non-cassava types with a 100% bootstrap probability. Analysis of molecular variance (AMOVA) of the RAPD fragments revealed that 63.2% of the total variation was attributable to differences among populations, while the differences among groups (host) and within populations accounted for 27.1 and 9.8% respectively. Analysis of the internally transcribed spacer region I (ITS 1) of the ribosomal DNA confirmed that the cassava populations of B. tabaci populations were distinct from non-cassava populations. Experiments to establish whitefly populations on various host plants revealed that cassava-associated populations were restricted to cassava only, whereas B. tabaci from other hosts were polyphagous but did not colonize cassava. Hence, populations of B. tabaci from cassava in Africa represent a distinct group.
APPLICATION OF GENERALIZED RADIAL BASIS FUNCTION NETWORKS TO RECOGNITION OF RADAR TARGETS
Authors: HUANG DE-SHUANG
Published: April 2003

This paper extends general radial basis function networks (RBFN) with Gaussian kernel functions to generalized radial basis function networks (GRBFN) with Parzen window functions, and discusses applying the GRBFNs to recognition of radar targets. The equivalence between the RBFN classifiers (RBFNC) with outer-supervised signals of 0 or 1 and the estimate of Parzen windowed probabilistic density is proved. It is pointed out that the I/O functions of the hidden units in the RBFNC can be extended to general Parzen window functions (or called as potential functions). We present using recursive least square-backpropagation (RLS–BP) learning algorithm to train the GRBFNCs to classify five types of radar targets by means of their one-dimensional cross profiles. The concepts about the rate of recognition and confidence in the process of testing classification performance of the GRBFNCs are introduced. Six generalized kernel functions such as Gaussian, Double-Exponential, Triangle, Hyperbolic, Sinc and Cauchy, are used as the hidden I/O functions of the RBFNCs, and the classification performance of corresponding GRBFNCs for classifying one-dimensional cross profiles of radar targets is discussed.
Ligand density modulates eosinophil signaling and migration
Authors: Holub A , Byrnes J , Anderson S , Dzaidzio L , Hogg N , Huttenlocher A
Published: April 2003

Eosinophils are a major component of the inflammatory response in persistent airway inflammation in asthma. The factors that determine the retention of eosinophils in the airway remain poorly understood. Elevated levels of fibronectin have been observed in the airway of patients with asthma, and the levels correlate with eosinophil numbers. To determine if fibronectin density modulates eosinophil function, we investigated the effect of fibronectin and vascular cell adhesion molecule 1 (VCAM-1) density on eosinophil migration and signaling via the p38 and extracellular regulated kinase (ERK)–mitogen-activated protein kinase (MAPK) signaling pathways. There was a dose-dependent inhibition of eosinophil spreading and migration on increasing concentrations of fibronectin but not VCAM-1. In addition, activation of p38 MAPK was inhibited at high fibronectin but not high VCAM-1 concentrations, and ERK activity was slightly reduced at high VCAM-1 and fibronectin concentrations. Together, the results demonstrate that fibronectin but not VCAM-1 inhibits eosinophil migration and signaling.
Phenotypic and functional analysis of T cells homing into the CSF of subjects with inflammatory diseases of the CNS
Authors: Giunti Debora , Borsellino Giovanna , Benelli Roberto , Marchese Monica , Capello Elisabetta , Valle Maria Teresa , Pedemonte Enrico , Noonan Douglas , Albini Adriana , Bernardi Giorgio , Mancardi Giovanni Luigi , Battistini Luca , Uccelli Antonio
Published: April 2003

The recruitment of lymphocytes across the blood brain barrier (BBB) is mediated by adhesion molecules and chemokines. The expression of activation markers and of chemokine receptors on T cells homing to the nervous system (NS) may help define their functional state. In the cerebrospinal fluid (CSF) of subjects with inflammatory neurological diseases (IND), including multiple sclerosis, we observed an increased number of T cells coexpressing CXCR3 and CCR5 as well as T cells with a CD45RO+ CCR7+ CD27+ memory phenotype. A subset of CCR7+ T cells coexpressed CXCR3 and CCR5. We also detected an increased number of interferon-γ-producing T cells in the CSF compared with peripheral blood, mostly but not exclusively in the CD45RO+ CCR7− CD27− compartment. T helper 1 (Th1) clones, established from the CSF of individuals with IND and from a healthy subject, similarly migrated to CXCL10, CXCL12, and CCL5. CXCL10, CXCL12, and CCL19 were increased in the CSF of individuals with neuroinflammation. These findings suggest that CSF is enriched in Th1-polarized memory T cells capable of differentiating into effector cells upon antigen encounter. These cells are recruited into the CSF by inducible chemokines. Thus, CSF represents a transitional station for T cells trafficking to and from the NS.
The prevalence of coeliac disease antibodies in patients with the antiphospholipid syndrome
Authors: Shamir R , Shoenfeld Y , Blank M , Eliakim R , Lahat N , Sobel E , Shinar E , Lerner A
Published: April 2003

High prevalence of coeliac disease (CD) has been reported in various autoimmune disorders, but has not been studied in the antiphospholipidsyndrome (APS). We aimed to establishthe prevalenceof CD antibodiesin a cohort of APS patients, and to examine whether CD may be responsiblefor some of the manifestationsof APS. Fifty-seven patients (47 females, 10 males) with APS were studied for clinical manifestations and serological markers of the disease, as well as the presence of anti-endomysial antibodies using an ELISA assay (EMA-ELISA). Control subjects were 171 healthy individuals, ageand sex-matched (141 females). Eight patients with APS (14%, six females) were found to have EMA-ELISA antibodies, compared with 2/141 (1.1%) of controls (P 0.0003). Antibodies against b2-glycoprotein-I (b2GPI) epitopes (GRTCPKPDDLP) were more prevalent in EMA-positive patients than in EMA-negative patients (P 0.006). Vasculitic skin lesions were significantly more common in EMA-ELISA-positive compared with EMA-ELISA-negative patients (62.5 versus 16.3%, P 0.01). Among the skin manifestations, superficial cutaneous necrosis (37.5 versus 2%, P 0.007) was more prevalent in EMA-ELISA-positive than in EMA-ELISA-negative patients. EMA-ELISA antibodies are common in APS, and their presence is associated with high prevalence of antibodies recognizing certain b2-glycoprotein epitopes, and with cutaneous manifestations of APS.
Glomerulosclerosis in Captive Cheetahs (Acinonyx jubatus)
Authors: Bolton L. A. , Munson L.
Published: April 2003

The cheetah ( Acinonyx jubatus) is an endangered species with low fecundity and premature death in captivity. A previous survey determined that renal failure as a result of glomerulosclerosis was a major cause of death in captive populations. This study characterizes the morphologic, histochemical, and epidemiologic properties of glomerulosclerosis in this population. Kidneys from 87 cheetahs were examined by light microscopy; kidneys from six of those cheetahs were examined by electron and fluorescent microscopy using special stains specific for collagen, glycoproteins, reticulin, and fibrin. Immunohistochemistry for the advanced glycosylation end products (AGEs), pyrraline and pentosidine, also was performed on these cases. Glomerulosclerosis was present to some degree in 82% of the population, and in 30% of cheetahs the sclerosis was moderate to severe. Affected cheetah kidneys had thickened glomerular and tubular basement membranes, culminating in glomerulosclerosis. Thickened basement membranes were positive for collagen, glycoproteins, reticulin, and AGEs. Ultrastructurally, membrane material was homogeneous and fibrillar without electron-dense deposits. This glomerular lesion in cheetahs resembles diabetic glomerulopathy in humans and chronic progressive nephropathy in rats. No cheetahs had lesions of diabetes. However, adrenal cortical hyperplasia was prevalent and highly correlated with glomerulosclerosis in this population. If cheetahs with glomerulosclerosis had hypercorticoidism, then hyperglycemia and glomerular hypertension could lead to progressive AGE and plasma protein accumulations in membrane lesions. As in rats, daily feeding of high-protein diets and lack of genetic variation in the population may further contribute to the high prevalence of glomerulosclerosis in captive cheetahs.
Helicobacter felis Infection in Dogs: Effect on Gastric Structure and Function
Authors: Simpson K. W. , McDonough P. L. , Strauss-Ayali D. , Chang Y.-F. , Harpending P. , Valentine B. A.
Published: April 2003

The relationship of Helicobacter felis, an organism that is observed in the stomachs of dogs, to gastric disease in dogs is unclear. The objective of this study was to determine if Helicobacter felis infection alters gastric morphology and gastric secretory function in dogs. Five specific-pathogen-free (SPF), Helicobacfer-free Beagle dogs were examined before and for 26 weeks after inoculation with H. felis (ATCC 49179). Three SPF uninfected dogs served as controls. All five dogs became colonized by H. felis as determined by urease activity, histopathology, polymerase chain reaction, and transmission electron microscopic examination of serial gastric biopsies. The degree of colonization ranged from <1 organism/400X field to >10 organisms/400 X field. The fundus, body, and cardia were most heavily colonized. Evaluation of gastric biopsies showed mild gastric inflammation and lymphoid follicles in both infected and uninfected dogs. There was no correlation between the number of organisms observed and the degree of gastric inflammation or number of lymphoid follicles. The gastric secretory axis, assessed by fasting and meal-stimulated plasma gastrin, mucosal gastrin and somatostatin immunoreactivity, fasting gastric pH, and pentagastrin-stimulated gastric acid secretion, was similar in both infected and uninfected dogs. Fasting gastric pH was not a reliable indicator of gastric secretory function. These findings suggest that H. felis may not be a gastric pathogen in dogs. However, the density of colonization and limited duration of infection should be considered when interpreting these findings.
Autosomal Trisomy 20 (61,XX,+20) in a Malformed Bovine Fetus
Authors: Gallagher D. S. , Lewis B. C. , Donato M. De , Davis S. K. , Taylor J. F. , Edwards J. F.
Published: April 2003

A 240-day-gestation female bovine fetus with severe anasarca, palatoschisis, cheiloschisis, mild cranioschisis, and a flattened facies was collected at a slaughterhouse, and a fibroblast line was established from the fetal skin. Chromosome preparations were Q-banded, and chromosome counts were taken that indicated the presence of 61 chromosomes in cells of the fetus (the normal diploid number for domestic cattle is 60). Q-band karyotypes were constructed, and Q-band analysis revealed the presence of three copies of chromosome 20. Trisomy 20 (61,XX,+20) was confirmed through the use of two-color fluorescence in situ hybridization of bovine bacterial artificial chromosome clones that were specific to chromosome 20 and the X chromosome.
Comparative Pathology and Pathogenesis of Spontaneous and Experimentally Induced Fibropapillomas of Green Turtles (Chelonia mydas)
Authors: Herbst L. H. , Jacobson E. R. , Klein P. A. , Balazs G. H. , Moretti R. , Brown T. , Sundberg J. P.
Published: April 2003

Tumor biopsy samples from 25 Floridian and 15 Hawaiian green turtles ( Chelonia mydas) with spontaneous green turtle fibropapillomatosis (GTFP) and from 27 captive-reared green turtles with experimentally induced GTFP were examined microscopically to differentiate the histologic features that result from GTFP pathogenesis and those that result from incidental factors that may vary according to geographic region. Common histologic features for spontaneous and experimentally induced tumors included fibroblast proliferation in the superficial dermis, epidermal acanthosis and hyperkeratosis, epidermal basal cell degeneration with dermal-epidermal cleft formation, spinous layer degeneration with intraepidermal vesicle and pustule formation, and ulceration. Visceral tumors, found in eight of 10 (80%) free-ranging turtles with cutaneous disease that were examined after death, had extensive interstitial fibrous proliferation. The presence of spirorchid trematode eggs and associated foreign body granulomas, common secondary findings within spontaneous tumors, varied by geographic location, and these findings were not observed in experimentally induced tumors. Eosinophilic intranuclear inclusions and intranuclear herpesvirus-associated antigen immunoreactivity were found in 18 of 38 (47%) experimentally induced cutaneous tumors and nine of 119 (7.5%) spontaneous tumors from Floridian but not Hawaiian turtles. The possible involvement of GTFP-associated herpesvirus in the pathogenesis of epidermal degenerative changes and GTFP pathogenesis is discussed.
A Case of Interstitial Pneumonia Associated with Pneumocystis carinii in a Foal
Authors: Lepage M.-F. Perron , Gerber V. , Suter M. M.
Published: April 2003

Subacute interstitial pneumonia with diffuse alveolar damage, marked macrophage infiltration, and intracellular Pneumocystis carinii cysts is described in a 3-month-old Swiss warmblood foal. Clinically, the disease was characterized by sudden onset of respiratory distress with fatal outcome. Based on serum immunoglobulin G (IgG), IgA, and IgM values, no humoral immunosuppression was detected. Spleen, thymus, and bronchial lymph nodes did not reveal lymphoid depletion, as assessed by immunohistochemical staining of CD-3-positive cells. Immunopathogenesis of pulmonary infections with intracellular agents in foals is discussed.