bluuebunny/crossref_metadata_2025_split huggingface dataset:
Projections from the paraventricular nucleus of the thalamus to the rat prefrontal cortex and nucleus accumbens shell: Ultrastructural characteristics and spatial relationships with dopamine afferents
Authors: Pinto Aline , Jankowski Michael , Sesack Susan R. 
Published: March 2003

AbstractThe paraventricular nucleus of the thalamus (PVT) participates in the functional integration of limbic cortical and striatal circuitry. In the rat, the PVT projects to the deep layers of the medial prefrontal cortex (PFC) and to the shell of the nucleus accumbens (NAc). However, the synaptic organization of PVT afferents within these regions remains undescribed. Furthermore, although dopamine (DA) modulates excitatory glutamate transmission in both areas, possible anatomic substrates for specific DA modulation of PVT inputs have not yet been investigated. To address these issues, immunoperoxidase labeling for tyrosine hydroxylase (TH) in DA axons was combined with anterograde tract‐tracing, either by biotinylated dextran amine (BDA) labeled with immunogold–silver or by degeneration after lesions of the PVT. In both regions, and with either tracing method, PVT terminals formed primarily asymmetric axospinous synapses; in the NAc, a proportion of PVT terminals also synapsed onto dendrites. PVT profiles in both regions were often seen in direct apposition to TH‐immunoreactive axons; this association was more evident in the NAc where the DA innervation is denser. Within the PFC, PVT profiles and TH‐labeled axons were occasionally apposed to the same dendrites, but synaptic specializations were not typically seen at these seeming points of convergence. Within the NAc, PVT profiles occasionally made synapses onto spines and distal dendrites that received convergent synapses from TH‐immunoreactive varicosities. These findings represent the first demonstration of postsynaptic convergence between DA and thalamic afferents to a striatal region and are consistent with direct synaptic modulation of PVT transmission by DA in the NAc but not the PFC. J. Comp. Neurol. 459:142–155, 2003. © 2003 Wiley‐Liss, Inc.
A composite statistical procedure for evaluating genotoxicity using cell transformation assay data
Authors: Nishiyama Hiroshi , Omori Takashi , Yoshimura Isao 
Published: March 2003

AbstractThis study proposes a statistical procedure for evaluating data from the BALB/c 3T3 cell transformation assay (CTA). Three steps are applied: (i) a Dunnett type test for identifying clear negativity, (ii) a Margolin procedure for detecting and eliminating downturn data, and (iii) a maximum contrast method for evaluating the dose‐dependent increase of the response. Using Monte Carlo simulation the proposed procedure was compared to three other methods, i.e. a linear regression test, the Simpson–Margolin procedure with linear regression test (trend test), and the Omori procedure. When false positive rates were commonly controlled at a similar level for all methods, the procedure's effectiveness was greatest for dose–response patterns exhibiting non‐linear and down turn parts, being in agreement with a collaborative CTA validation study performed in Japan. Evaluation of CTA data by the proposed procedure satisfied participating researchers. Copyright © 2003 John Wiley & Sons, Ltd.
Toxicokinetic modeling for environmental health problems
Authors: Edler Lutz , Heinzl Harald 
Published: March 2003

AbstractToxicokinetic (TK) and physiologically based toxicokinetic (PB‐TK) models enable tissue dosimetry and the definition of the target organ dose after exposure to exogenous toxic compounds. This has qualified PB‐TK models for extrapolation from the experimental animal to the human, from high to low doses, between routes of exposure, between patterns of exposure, and also between robust and susceptible sub‐populations. We show how PB‐TK models are constructed, what assumptions are needed, which mathematical methods are used for model building and by which statistical methods one may assess both model fit and uncertainty of the modeling itself. We will address in particular a new generation of PB‐TK models which include age‐dependent model parameters to model life‐long human exposure with an example from the exposure to dioxins. Finally, we define the role of PB‐TK models for the identification of human health effects after exposure to chemicals in risk assessment. Copyright © 2003 John Wiley & Sons, Ltd.
HLA‐B*15 diversity in the Korean population
Authors: Lee K.W. , Jeon H. , Park J.Y. 
Published: March 2003

Acknowledgments:This research was supported by a grant (KOSEF 981‐0701‐002‐2) from the Basic Research Program of the KOSEF. We thank Dr. C. K. Hurley at Georgetown University for the generous gift of some reference DNAs as well as for a critical review of the manuscript, and Miss J. S. Lee for technical assistance.Abstract:Alleles in the HLA‐B*15 group encode molecules belonging to several serologic subgroups, B15 (B62, B63, B75, B76, B77) and B70 (B71, B72), representing many of the most problematic types to assign in routine clinical typing laboratories due to their serologic cross‐reactivity resulting from structural similarity. More than 25% of Koreans express HLA‐B molecules encoded by the HLA‐B*15 alleles. To further characterize HLA‐B*15 in this population, B*15‐specific polymerase chain reaction (PCR) and sequence‐specific oligonucleotide probe (SSOP) hybridization analysis using 39 digoxigenin‐labeled probes were applied to DNA samples obtained from 237 B15/B70 serologically positive unrelated individuals. Nine B*15 alleles were identified. B*1501 was the most frequent allele (64.8%) followed by B*1511 (14.1%), B*1507 (8.6%), and B*1518 (5.5%) comprising more than 90% of B*15‐positive samples. B62 molecules encoded by 4 of the identified alleles (B*1501, B*1507, B*1525, and B*1527) could not be discriminated by serologic reaction patterns. Among the fifteen B15/B70 apparent homozygotes, eight were heterozygotes carrying two different B*15 alleles. Several B*15 alleles exhibited strong associations with specific Cw, DRB1, and A allelic types (e.g., B*1507‐Cw3 (22/22); B*1507‐DRB1*04 (21/22), B*1507‐A24 (17/22)). The data obtained in this study confirmed B*15 diversity in the study population and will be useful in hematopoietic stem cell donor searches as well as in determining the supplementary DNA typing strategy for B15/B70‐positive samples in this population.
Downregulation of the constitutive tapasin expression in human tumor cells of distinct origin and its transcriptional upregulation by cytokines
Authors: Seliger B. , Schreiber K. , Delp K. , Meissner M. , Hammers S. , Reichert T. , Pawlischko K. , Tampé R. , Huber CH. 
Published: March 2003

Abstract:Human tumor cells frequently exhibit abnormalities in the major histocompatibility complex (MHC) class I surface expression which can be due to structural alterations and/or dysregulation of various components of the MHC class I antigen processing machinery, such as HLA class I heavy and light chains, the peptide transporter and the proteasome subunits. Although several cofactors critical for proper MHC class I assembly have been identified, their contribution to the immune escape phenotype of tumor cells has not been analyzed. In order to determine whether tapasin deficits are an integral part of immune escape mechanisms of human tumors, we studied the constitutive and cytokine‐regulated expression pattern of tapasin in malignant cells of distinct histology. Heterogeneous and reduced expression levels of tapasin were found in small‐cell lung carcinoma, pancreatic carcinoma, colon carcinoma, head an neck squamous cell carcinoma and renal cell carcinoma cell lines. Tapasin downregulation was also prominent in surgically removed tumor lesions when compared to normal controls. The impaired tapasin expression is often associated with low MHC class I cell surface expression. In addition, various cytokines, including interferon (IFN)‐α, IFN‐γ, tumor necrosis factor (TNF)‐α and interleukin (IL)‐4, but not granulocyte‐macrophage colony stimulating factor (GM‐CSF), transcriptionally upregulate to a distinct extent and in a time‐dependent manner tapasin expression in tumor cells. Thus, deficient tapasin expression appears to be a frequent event in human tumor cells. Its restoration by cytokines further suggests that impaired tapasin expression in tumors is rather due to dysregulation than to structural alterations.
Is the infiltration‐centrifugation technique appropriate for the isolation of apoplastic fluid? A critical evaluation with different plant species
Authors: Lohaus Gertrud , Pennewiss Kerstin , Sattelmacher Burkhard , Hussmann Melanie , Hermann Muehling Karl 
Published: March 2003

The suitability of the infiltration‐centrifugation method for collection of apoplastic fluid from intact leaves was evaluated for different plant species. Large differences with respect to infiltrability of the leaves, which correlated inversely with stomatal and mesophyll resistance, became apparent. Osmolality of infiltration medium (deionised water, 0.2 mM CaCl2, 10 mM KCl, 180 mM 2‐[N‐morpholino]ethane‐sulphonic acid) and incubation time, time passed between onset of infiltration and end of centrifugation, revealed relatively little influence on the composition of the apoplastic washing fluid (AWF). In contrast, the pH of the infiltrated solution highly influenced the concentration of sucrose and hexoses. With increasing centrifugation force, hexosephosphate isomerase (HPI) activity in the AWF, which was taken as an indication for cytoplasmic contamination, increased. At the same time, Ca2+ concentration in the AWF increased even more. Since Ca2+ cannot originate from the cytoplasm, the suitability of HPI as marker for cytoplasmic contamination is questioned. From the composition of the AWF, it is concluded that, if centrifugation force does not exceed 1

000 g, cytoplasmic contamination is negligible and that the infiltration‐centrifugation technique reveals an easy and inexpensive way to study apoplastic solutes. The infiltration‐centrifugation method was also suitable to determine apoplastic air volume (Vair) and apoplastic water volume (Vwater), which are necessary for the calculation of the ion concentration in the leaf apoplast. It could be shown that the leaves of different species and the apical and basal leaves of single plants differ in Vair and Vwater.
Immunopathogenesis of hepatitis C virus in the immunosuppressed host
Authors: Einav S. , Koziel M.J. , Einav Koziel S., M.J. 
Published: March 2003

Abstract:The prevalence of chronic hepatitis C virus (HCV) infection among various groups of immunosuppressed patients is high. These groups include patients co‐infected with human immunodeficiency virus (HIV), recipients of organ transplants, and those with hypogammaglobulinemia. The liver disease in the immunosuppressed host is typically severe with an unusually rapid progression to cirrhosis. This is somewhat paradoxical, as the classical model for HCV‐induced liver disease assumes that cell‐mediated immune responses induce liver injury. It is likely that a combination of viral‐related factors and host‐related factors plays a role in this accelerated natural history of HCV. Data are accumulating in immunocompromised hosts that address the immunopathogenesis of liver injury, although there are still fundamental gaps in our understanding of this process. In this review, we will focus on our current understanding of the mechanisms of liver injury and how it relates to the accelerated liver disease progression in immunocompromised hosts.
Intravenous synthetic αgal saccharides delay hyperacute rejection following pig‐to‐baboon heart transplantation
Authors: Romano Egidio , Neethling Francisca A. , Nilsson Kurt , Kosanke Stanley , Shimizu Akira , Magnusson Stefan , Svensson Lola , Samuelsson Bo , Cooper David K. C. 
Published: March 2003

Romano E, Neethling FA, Nilsson K, Kosanke S, Shimizu A, Magnusson S, Svensson L, Samuelsson B, Cooper DKC Intravenous synthetic αgal saccharides delay hyperacure rejection following pig‐to‐baboon heart transplantation. Xenotransplantation 1999; 6: 00‐00Several oligosaccharides containing the terminal structure Galα1–3Gal (αGal) and different side chains were tested in vitro for their ability to block natural antiαGal antibodies. A di‐and a trisaccharide (diαGal and triαGal) were selected. A blood group B baboon, having IgG and IgM natural antipig titers of 1 : 256 and 1 : 1024 and a hemolytic titer (to pig red blood cells, RBCs) of 1 : 8, was chosen to measure pharmacokinetic parameters of the saccharides and to assess the extent of in vivo neutralization of the antibodies. Three grams each of the diαGal and the triαGal dissolved in saline were administered by bolus intravenous (i.v.) injection. Blood samples were collected at various times and urine was collected at 8 and 24 h. Plasma and urine concentrations of the αGal saccharides were estimated by an ELISA specially developed for this study. A fast distribution phase followed by equilibrium and excretion phases were observed, indicating a T1/2 in the order of 1 h. Fifty‐eight per cent of the saccharides were recovered in the urine within 24 h. Determination of antipig antibody binding by FACS analysis and of serum cytotoxicity titers for pig endothelial cells demonstrated that a 70% reduction in binding and cytotoxicity could be achieved with plasma saccharide levels of 300–400 µg/ml. Six months later, a pig heart was transplanted heterotopically into the baboon. A 3‐g bolus of the saccharide mixture (1.5 g of each saccharide) was given i.v. before allowing blood reperfusion of the transplanted heart, followed by an i.v. infusion of 1 g/hr for 1 hr and 0.5 g/hr for the 3 succeeding hours. Blood concentrations of the saccharides, CH50, hematology and cytotoxicity for PK15 cells were estimated in blood samples taken at various times. Heart function was observed to be satisfactory for 8 h, but was found to have ceased at 18 h. Myocardial biopsies taken at 3 and 5 h showed congestion only, suggestive of minimal vascular rejection, but by 18 h demonstrated severe vascular rejection. In conclusion, αGal saccharide therapy given for a period of 4 h delayed, but did not totally prevent, the development of vascular rejection in the pig‐to‐baboon heart transplant model. αGal saccharide therapy may be one of several useful approaches for the prevention of hyperacute rejection in pig‐to‐primate organ transplantation.
Different morphotypes of the tabby (EDA) dentition in the mouse mandible result from a defect in the mesio‐distal segmentation of dental epithelium
Authors: Peterková R , Kristenová P , Lesot H , Lisi S , Vonesch J‐L , Gendrault J‐L , Peterka M 
Published: March 2003

Structured Abstract
Authors –
Peterková R., Kristenová P., Lesot H., Lisi S., Vonesch J‐L., Gendrault J‐L., Peterka M.
Objectives –
Prenatal identification of the different dentition morphotypes, which exist in the lower molar region of tabby (Ta) adult mice, and investigation of their origin. The mouse Ta syndrome and its counterpart anhidrotic (hypohidrotic) ectodermal dysplasia (EDA) in human are characterized by absence or hypoplasia of sweat glands, hair and teeth.
Design –
Analysis of tooth morphogenesis using serial histological sections and 3D computer aided reconstructions of the dental epithelium in the cheek region of the mandible.
Setting and Sample Population –
Institute of Experimental Medicine, Academy of Sciences, Prague. Heads of 75 Ta homozygous and hemizygous mice and 40 wild type (WT) control mice aged from embryonic day (ED) 14.0–20.5 (newborns), harvested during 1995–2001.
Outcome Measure –
Prenatal identification of five distinct morphotypes of Ta dentition on the basis of differences in tooth number, size, shape, position and developmental stage and of the morphology of the enamel knot in the most mesial tooth primordium.
Results –
The mesio‐distal length of the dental epithelium was similar in the lower cheek region in Ta and WT mice. In Ta embryos, there was altered the mesio‐distal segmentation of the dental epithelium giving rise to the individual tooth primordia. Prenatally, two basic morphotypes I and II and their particular subtypes (Ia, Ib, Ic, and IIa, IIb, respectively) of the developing dentition were identified from day 15.5. The incidence of the distinct morphotypes in the present sample did not differ from postnatal data. The proportion of the morphotype I and II was dependent on mother genotype.
Conclusion –
The different dentition morphotypes in Ta mice originate from a defect in the mesio‐distal segmentation of the dental epithelium in mouse embryos. This defect presumably leads to variable positions of tooth boundaries that do not correspond to those of the WT molars. One tooth primordium of Ta mice might be derived from adjacent parts of two molar primordia in WT mice.
The supportive role of complement in HIV pathogenesis
Authors: Stoiber H. , Kacani L. , Speth C. , Würzner R. , Dierich M. P. 
Published: March 2003

Summary:This review focuses on interactions of HIV with the first‐line defence of native immunity, the complement system. In all body compartments tested so far, HIV meets complement. Activation of the complement system results in deposition of C3 fragments on the viral surface, but in contrast to other pathogens, most of HIV is not or is only poorly lysed by membrane attack complexes. To survive complement‐mediated lysis, HIV has not only developed resistance mechanisms, but uses opsonisation with complement fragments for its own advantage. Opsonised virions interact with complement receptor‐expressing cells, which are either subsequently infected with high efficiency or retain viral particles on their surface, which promotes transmission of virus to other permissive cells. Our knowledge of these mechanisms has increased enormously over the past few years. A complete understanding of these complex interactions of HIV with the complement system opens new perspectives for development of alternative therapeutic strategies.We like to thank Anke Stoiber for secretarial support. This work was supported in part by grants from the FWF (P14070‐MED; P13182‐MOB), the OENB (Jubiläumsfonds Nr. 8504), the 5th Frame Work of the EU (QLK 2‐1999‐01215), the State of Tyrol and Federal Ministeries.
Specificity and function of activating Ly‐49 receptors
Authors: Kane Kevin P. , Silver Elizabeth T. , Hazes Bart 
Published: March 2003

Summary: Inhibitory Ly‐49 receptors allow murine natural killer (NK) cells to kill cells with aberrant class I MHC expression while sparing normal cells. This is accomplished by their recognition of specific class I MHC products and prevention of NK‐cell lysis of cells that present a normal repertoire of class I MHC ligands –“the missing self hypothesis”. However, Ly‐49 receptors that lack the cytoplasmic immunoreceptor tyrosine‐based inhibitory motif, which is required for inhibition of killing, have also been described. These receptors were found to stimulate NK killing and are therefore referred to as activating Ly‐49 receptors. Interestingly, the activating receptors have class I MHC‐binding domains that are nearly indistinguishable from those of the inhibiting receptors, and binding to class I MHC has now been demonstrated for three activating receptors. Presently, there is no defined physiological role for activating Ly‐49 receptors. Here we present an overview of current knowledge regarding the diversity, structure and function of activating Ly‐49 receptors with a focus on class I MHC specificity, and we discuss their potential role(s) in natural resistance.This research was supported by an operating grant from the National Cancer Institute of Canada and the Canadian Cancer Society (K. P. Kane) and a Canadian Institutes for Health Research operating grant (B. Hazes). E. Silver is supported by an Alberta Heritage Foundation for Medical Research (AHFMR) studentship and K. P. Kane is an (AHFMR) senior scholar.
Thermodynamic studies of some Fe‐Pt alloys by the solid electrolyte galvanic cell method
Authors: Fredriksson Patrik , Seetharaman Seshadri 
Published: March 2003

In the present investigation, the thermodynamic activities of iron in iron‐platinum solid alloys were measured by the solid electrolyte galvanic cell method in the temperature range 1073–1273 K. The galvanic cell employed can be represented as(−) Pt, Fe(s), FetO(s) // ZrO2(11 mol pct CaO) //FetO(s), Fe‐Pt alloys, Pt(+)The experimental set‐up as well as the satisfactory performance of the galvanic cell were validated by measuring the standard Gibbs energy of formation of CoO in equilibrium with Co in the same temperature range by replacing the working electrode by a Co, CoO mixture. 6 different Fe‐Pt alloys covering the entire composition range were studied and the results are compared with earlier thermodynamic studies available in the literature. The present experimental results are found to be in general agreement with those of Alcock and Kubik. The values were fitted into a regular solution description in order to estimate the enthalpies of mixing Pt and Fe in the solid alloys.
Expression of inducible nitric oxide synthase and heat shock proteins in periapical inflammatory lesions
Authors: Suzuki Takahiro , Kumamoto Hiroyuki , Ooya Kiyoshi , Motegi Katsutoshi 
Published: March 2003

AbstractBackground:  The mechanisms responsible for activation and proliferation of lining epithelium involved in inflammatory processes in periapical inflammatory lesions remain unclear. In this study, the expression and distribution of inducible nitric oxide synthase (iNOS) and heat shock proteins (HSPs) were immunohistochemically investigated in periapical inflammatory lesions.Methods:  Control specimens of periodontal ligaments including Malassez epithelial rests from seven teeth and periapical inflammatory lesions (15 apical granulomas (AGs), 16 radicular cysts (RCs), and 10 residual radicular cysts (RRCs)) were prepared and examined by the standard streptavidin–biotin peroxidase complex method using anti‐iNOS rabbit polyclonal antiserum, and anti‐HSP27, ‐HSP60, ‐HSP70 mouse monoclonal antibodies.Results:  Immunoreactivity for iNOS was detected in macrophages, lymphocytes, and endothelial cells of granulation tissue and in lining epithelium of periapical inflammatory lesions. Malassez epithelial rests showed no or slight staining for iNOS. The epithelial staining intensity of iNOS in RCs was greater than that in Malassez epithelial rests and RRCs. Immunoreactivity for HSP27 was recognized in inflammatory cells, endothelial cells and lining epithelium of periapical inflammatory lesions and in Malassez epithelial rests. HSP60 was detected in some lymphocytes of granulation tissue and in lining epithelium of periapical inflammatory lesions, whereas Malassez epithelial rests showed no staining for HSP60. Epithelial HSP60 reactivity was more intense in RCs than in RRCs. HSP70 was expressed in lymphocytes, endothelial cells and lining epithelium of periapical inflammatory lesions and in Malassez epithelial rests. The staining intensity of HSP70 in Malassez epithelial rests was slightly lower than that in lining epithelium of RCs and RRCs.Conclusions:  These data demonstrate that the expressions of iNOS, HSP60, and HSP70 are involved in inflammatory processes and might play a role in the activation and proliferation of lining epithelium, leading to progression of periapical inflammatory lesions.