bluuebunny/crossref_metadata_2025 huggingface dataset:
CD40 ligation of rheumatoid synovial fibroblasts regulates RANKL‐medicated osteoclastogenesis: Evidence of NF‐κB–dependent, CD40‐mediated bone destruction in rheumatoid arthritis
Authors: Lee Hak‐Yong , Jeon Hyun‐Soon , Song Eun‐Kyung , Han Myung‐Kwan , Park Sung‐Il , Lee Sang‐Il , Yun Hee‐Jin , Kim Jung‐Ryul , Kim Jong‐Suk , Lee Yong‐Chul , Kim Sung‐Il , Kim Hang‐Rae , Choi Jin‐Young , Kang Insoo , Kim Ho‐Youn , Yoo Wan‐Hee
Published: May 2006

Objective

To determine whether CD40 ligation of rheumatoid arthritis synovial fibroblasts (RASFs) is able to induce RANKL expression and osteoclastogenesis in RASFs, and to identify its mechanism of action in patients with RA.

Methods

CD40 of RASFs was ligated with CD40 ligand (CD40L)–transfected L cells or activated T cells. The formation of osteoclasts in cocultures of CD40‐ligated RASFs and T lymphocyte–depleted peripheral blood mononuclear cells was evaluated by tartrate‐resistant acid phosphatase staining, detection of calcitonin receptor, and resorption pit formation assay. The expression of NF‐κB, IκBα, ERK‐1/2, phospho‐ERK‐1/2, p38, phospho‐p38, and RANKL was examined by immunoblotting and/or semiquantitative reverse transcription–polymerase chain reaction.

Results

CD40 ligation of RASFs by CD40L‐transfected L cells or activated T cells induced RANKL expression and enhanced osteoclastogenesis. CD40 ligation of RASFs also induced activation of ERK‐1/2, p38 MAPK, and NF‐κB and up‐regulation of CD40 ligation–induced RANKL expression, whereas osteoclastogenesis was reduced in RASFs transfected with a dominant‐negative mutant of IκBα or by an NF‐κB inhibitor. However, specific inhibitors of MAPK/ERK‐1/2 and p38 MAPK partially blocked the induction of RANKL expression and osteoclastogenesis. Monoclonal antibodies against interleukin‐1 and tumor necrosis factor α partially inhibited CD40 ligation–mediated osteoclastogenesis.

Conclusion

These results indicate that CD40 ligation of RASFs induces RANKL expression mainly via NF‐κB activation and also results in enhanced osteoclast formation, both of which might play important roles in bone and cartilage destruction in RA. Inhibition of the CD40–CD40L interaction is a potential strategy for the prevention of bone damage in RA.
Effects of vibration and hyaluronic acid on activation of three‐dimensional cultured chondrocytes
Authors: Takeuchi Ryohei , Saito Tomoyuki , Ishikawa Hiroyuki , Takigami Hidetake , Dezawa Mari , Ide Chizuka , Itokazu Yutaka , Ikeda Mitsugu , Shiraishi Toshihiko , Morishita Shin
Published: May 2006

Objective

To investigate the effects of vibration (Vib) and hyaluronic acid (HA) on 3‐dimensional cultured cartilage.

Methods

Chondrocytes were obtained from metatarsophalangeal joints of freshly killed 6‐month‐old pigs. Twenty‐four–well plates containing type I collagen sponge disks were used to culture samples. The frequency and the amplitude of the vibration of the well plate were 100 Hz and 0.5 nm, respectively. We produced 3‐dimensional cartilage tissue using HA and vibration with collagen sponge as a carrier. Four different culture conditions were examined: a control HA−Vib− group, an HA−Vib+ group, an HA+Vib− group, and an HA+Vib+ group. Each group was cultured for 2 weeks. After culture days 3, 7, 10, and 14 (every 3.5 days), the levels of chondroitin 4‐sulfate (C4S) and chondroitin 6‐sulfate (C6S) isomers synthesized in each culture medium were measured. Histologic analysis, immunohistochemical analysis, and electron microscopic examination were performed.

Results

Mean C4S and C6S synthesis had increased rapidly after 7 days of culture and continued to increase thereafter. There were significant differences among the 4 groups (P < 0.01). Synthesis of both C4S and C6S was most abundant in the HA+Vib+ group and the lowest in the HA−Vib− group. After 1 and 2 weeks of culture, the chondrocytes had formed stratified structures on the collagen sponges in all groups, although the thickest structure was observed in the HA+Vib+ group and the thinnest in the HA−Vib− group. Under immunofluorescence, the HA+Vib+ group exhibited the strongest chromatic features. Under electron microscopy, the chondrocytes in the HA+Vib+ group exhibited many long and slender prominences on their surface, and extracellular substance could be observed associated with the cells.

Conclusion

Our results indicate that the combination of vibration and HA activates the production of proteoglycan in 3‐dimensional cultured chondrocytes and stimulates MAPK and β‐catenin. This suggests that some mechanoreceptors for vibration exist on the plasma membrane of chondrocytes and activate the intracellular signal transduction system.
Combination immunotherapy with prostatic acid phosphatase pulsed antigen‐presenting cells (provenge) plus bevacizumab in patients with serologic progression of prostate cancer after definitive local therapy
Authors: Rini Brian I. , Weinberg Vivian , Fong Lawrence , Conry Shauna , Hershberg Robert M. , Small Eric J.
Published: May 2006

BACKGROUND

APC8015 (sipuleucel‐T) is a cellular prostate cancer vaccine containing autologous antigen‐presenting cells (APC) loaded with PA2024, a recombinant prostatic acid phosphatase/granulocyte‐macrophage–colony‐stimulating factor fusion protein, as the immunogen. Bevacizumab is a recombinant antibody against vascular endothelial growth factor, a proangiogenic protein with inhibitory effects on APC. A clinical trial was conducted to determine the prostate‐specific antigen (PSA) and immunomodulatory effects of this combination immunotherapy.

METHODS

Patients with androgen‐dependent prostate cancer who had received prior definitive therapy with nonmetastatic, recurrent disease as manifested by a rising PSA of between 0.4 ng/mL and 6.0 ng/mL were enrolled. APC8015 was given intravenously(i.v.) on Weeks 0, 2, and 4. Bevacizumab was given at a dose of 10 mg/kg i.v. on Weeks 0, 2, 4, and every 2 weeks thereafter until toxicity or disease progression. PSA changes were recorded and the PSA doubling time (PSADT) was calculated. Immune response versus PA2024 was measured at baseline and after treatment by T‐cell proliferation and interferon‐γ enzyme‐linked immunospot (ELISPOT) assays.

RESULTS

Twenty‐two patients were treated. One patient achieved a ≥50% decrease in PSA. Nine patients exhibited some decrease in PSA from baseline, ranging from 6% to 72%, with the PSA of 3 patients decreasing at least 25%. The median pretreatment PSADT for the 20 evaluable patients was 6.9 months and the median posttreatment PSADT was 12.7 months (P = .01). All patients demonstrated induction of an immune response against PA2024.

CONCLUSIONS

The combination of APC8015 and bevacizumab induces an immune response and modulates PSA in patients with biochemically recurrent prostate cancer. Cancer 2006. © 2006 American Cancer Society.
Changes inD‐serine levels and localization during postnatal development of the rat vestibular nuclei
Authors: Puyal Julien , Martineau Magalie , Mothet Jean‐Pierre , Nicolas Marie‐Thérèse , Raymond Jacqueline
Published: May 2006

The patterns of development of the vestibular nuclei (VN) and their main connections involving glutamate neurotransmission offer a good model for studying the function of the glial‐derived neuromodulatorD‐serine in synaptic plasticity. In this study we show thatD‐serine is present in the VN and we analyzed its distribution and the levels of expression of serine racemase andD‐amino acid oxidase (D‐AAO) at different stages of postnatal (P) development. From birth to P21, high levels ofD‐serine were detected in glial cells and processes in all parts of the VN. This period corresponded to high expression of serine racemase and low expression ofD‐AAO. On the other hand, in the mature VND‐serine displayed very low levels and was mainly localized in neuronal cell bodies and dendrites. This drop ofD‐serine in adult stages corresponded to an increasing expression ofD‐AAO at mature stages. High levels of glialD‐serine during the first 3 weeks of postnatal development correspond to an intense period of plasticity and synaptogenesis and maturation of VN afferents, suggesting thatD‐serine could be involved in these phenomena. These results demonstrate for the first time that changes inD‐serine levels and distribution occur during postnatal development in the central nervous system. The strong decrease ofD‐serine levels and the glial‐to‐neuronal switch suggests thatD‐serine may have distinct functional roles depending on the developmental stage of the vestibular network. J. Comp. Neurol. 497:610–621, 2006. © 2006 Wiley‐Liss, Inc.
Chemical composition of essential oils from aerial parts of Aframomum exscapum (Sims) hepper collected in Guadeloupe, French West Indies
Authors: de K. Martin M. A. Couppé , Joseph H. , Bercion S. , Menut C.
Published: May 2006

Chemical composition of essential oils obtained by hydrodistillation of leaves, stems, pulp and seeds of fruits of Aframomum exscapum (Sims) Hepper grown in Guadeloupe was investigated by GC and GC–MS. Forty‐four volatile compounds were identified, among which 1,8‐cineole was the main constituent in all parts of the plant (47–86%). These analytical data confirm that the species from Guadeloupe is not Aframomum melegueta (Rosc.) K. Schum. as initially claimed by local botanists. Copyright © 2006 John Wiley & Sons, Ltd.
Thyroid cancer and employment as a radiologic technologist
Authors: Zabel Erik W. , Alexander Bruce H. , Mongin Steven J. , Doody Michele M. , Sigurdson Alice J. , Linet Martha S. , Freedman D. Michal , Hauptmann Michael , Mabuchi Kiyohiko , Ron Elaine
Published: May 2006

The association between chronic occupational ionizing radiation exposure in the medical field and thyroid cancer is not well characterized. Thyroid cancer incidence was ascertained for 2 periods in a cohort of radiologic technologists certified for a minimum 2 years and enumerated in 1983: (i) cases identified prospectively in 73,080 radiologic technologists who were free of thyroid cancer at the baseline survey and completed a second questionnaire a decade later (N = 121), and (ii) cases occurring prior to cohort enumeration among 90,245 technologists who completed the baseline survey and were thyroid cancer free 2 years after certification (N = 148). Survival analyses estimated risks associated with employment as a radiologic technologist, including duration of employment, period of employment, types of procedures and work practices. The only occupational history characteristic associated with prospectively identified thyroid cancer was a history of holding patients for X‐ray procedures at least 50 times (HR = 1.47, 95% CI = 1.01–2.15). Total years worked as a radiologic technologist, years performing diagnostic, therapeutic, and nuclear medicine procedures, employment under age 20 and calendar period of first employment were not associated with thyroid cancer risk. Risk of thyroid cancers diagnosed before the baseline questionnaire was inversely associated with decade first employed as a technologist, and was elevated, albeit imprecisely, among those working more than 5 years prior to 1950 (HR = 3.04, 95% CI = 1.01–10.78). These data provide modest evidence of an association between employment as a radiologic technologist and thyroid cancer risk; however, the findings require confirmation with more accurate exposure models. © 2006 Wiley‐Liss, Inc.
Peritoneal application of chitosan and UV‐cross‐linkable chitosan
Authors: Yeo Yoon , Burdick Jason A. , Highley Christopher B. , Marini Robert , Langer Robert , Kohane Daniel S.
Published: May 2006

The suitability of chitosan and UV‐cross‐linkable chitosan for intraperitoneal use, for example as a barrier device for preventing peritoneal adhesions or for drug delivery, was examined. In vitro experiments using two major cell types present in the peritoneal cavity (mesothelial cells and peritoneal macrophages) revealed neither attractive interactions between cross‐linked chitosan gels and the cells nor a proliferative effect. However, the same UV‐cross‐linked chitosan applied in the peritoneal cavity of rabbits caused a granulomatous reaction with adhesion formation within two weeks in all animals, which persisted up to 4 weeks after exposure. Unmodified chitosan also caused adhesions, while UV irradiation did not. UV‐cross‐linkable chitosan induced significant elevations in MIP‐2 and TNF‐α from peritoneal macrophages, suggesting that soluble mediators could play a role in inducing adhesion formation. These results reinforce the view that the predictive value of in vitro cytotoxicity assays in matters of biocompatibility may not be sufficient, and suggest that other assays such as cytokine levels may be of value in predicting outcomes in situations involving multiple cell types (i.e. in vivo). © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Nanoindentation differentiates tissue‐scale functional properties of native articular cartilage
Authors: Li Cheng , Pruitt Lisa A. , King Karen B.
Published: May 2006

Cartilage mechanical properties are typically tested at the macroscale. To demonstrate the ability of nanoindentation to characterize in situ articular cartilage properties at the tissue scale, we investigated the local structure–property relationships of intact articular cartilage of a normal rabbit metacarpophalangeal joint. We calculated the mechanical parameters of stiffness, S, resistance to penetration, R, and volumetric creep strain, dV/V, from nanoindentation of the articular surface at specific regions of interest. We measured morphological parameters of superficial zone thickness, middle zone thickness, total uncalcified thickness, and cell density from corresponding regions with light and polarized light microscopy. Mechanical parameters were compared to morphological parameters. There were significant positive correlations (r = 0.98, p < 0.05) between superficial zone thickness and both S and R. However, we found no significant correlation between dV/V and the zone sizes. There were moderate, negative correlations between cell density and both S and R, suggesting an effect of cell volume on cartilage behavior at the tissue scale. We opine that the superficial zone plays important role in load support, as evidenced by correlations between zone size and intact cartilage mechanical properties. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Thyroid hormone metabolism and peroxidase function in two non‐chordate animals
Authors: Heyland Andreas , Price David A. , Bodnarova‐buganova Michaela , Moroz Leonid L.
Published: May 2006

In mammals, thyroid hormone (TH) signaling is essential for metabolic control, differentiation and homeostasis. These hormones are also involved in the regulation of metamorphosis in amphibians and lampreys and a role in basal chordates has been suggested. Increasing evidence supports TH‐related function not only in basal chordates such as urochordates and cephalochordates but also in other invertebrate groups. However, the regulatory mechanisms underlying TH function including the mechanisms of endogenous synthesis of hormones in these groups are essentially unknown. Our data provide evidence for endogenous TH synthesis in the sea hare Aplysia californica and the sea urchin Lytechinus variegatus based on thin layer chromatography. Pharmacological experiments show that these hormones accelerate development to metamorphosis and specifically affect the formation of juvenile skeletal structures in the sea urchin. Furthermore, we identified two new peroxidase genes (LvTPO from L. variegatus and AcaTPO from A. californica) showing high sequence similarity with peroxidasin and thyroid peroxidases (the critical TH synthesis enzymes found in all vertebrates). Spatial and temporal expression patterns of these transcripts suggest a role of LvTPO and AcaTPO in a variety of processes such as development to metamorphosis and the regulation of the animal's energetics. We discuss our new findings in the context of evolution of TH synthesis and TH signaling in non‐chordate animals. J. Exp. Zool. (Mol. Dev. Eiol.) 306B, 2006. © 2006 Wiley‐Liss, Inc.
Detection of weakly interacting anti‐carbohydrate scFv phages using surface plasmon resonance
Authors: Åström Eva , Ohlson Sten
Published: May 2006

Methods to characterise and confirm specificity of scFv displayed on phages are important during panning procedures, especially when selecting for antibody fragments with weak affinities in the millimole to micromole range. In this report the surface plasmon resonance (SPR) biosensor was used to study and verify specificity of phages displaying weak anti‐carbohydrate scFvs. The variable immunoglobulin light (VL) and heavy (VH) chain genes of the weak monoclonal antibody 39.5 were amplified and cloned into a phagemid and displayed as a scFv‐pIII fusion protein on filamentous phage. This monoclonal antibody recognises with weak affinity the structural sequence Glcα1‐4Glc present in a variety of carbohydrate molecules. Injection of the 39.5 phages over a biosensor chip immobilised with a (Glc)4‐BSA conjugate confirmed selective binding of the scFv to its antigen. Inhibition studies verified the specificity. These results clearly show that SPR technology can be used to evaluate in terms of binding and specificity weakly interacting scFv displayed on the phage surface. Copyright © 2006 John Wiley & Sons, Ltd.
Selective laser nano‐thermolysis of human leukemia cells with microbubbles generated around clusters of gold nanoparticles
Authors: Lapotko Dmitri O. , Lukianova Ekaterina , Oraevsky Alexander A.
Published: May 2006

Background and Objective

Previously reported studies on laser nano‐thermolysis of cancerous cells demonstrated insufficient efficacy and specificity of malignant cell damage. Safety, that is, absence of damage to normal cells in the course of the laser thermolysis was also low due to less than optimal protocol of cancer cell targeting with nanoparticles (NP). The objective of this study was two‐fold: to optimize NP targeting to real tumor (human) cells and to better understand physical mechanisms of cell damage for improved control of the laser ablation.

Study Design/Materials and Methods

We have suggested (1) two‐stage targeting method to form clusters of light‐absorbing gold NPs selectively in target cells, and (2) the cell damage mechanism through laser‐induced generation of vapor bubbles around NP clusters. Experimental investigation of laser nano‐thermolysis of leukemia cells was performed using 30 nm spherical gold nanoparticles as a light absorbing agent, and photothermal and fluorescent microscopies as well as flow cytometry as methods to monitor microbubble formation and resulting damage of leukemia cells in human bone marrow specimens.

Results

NP clusters were formed and visualized using fluorescence microscopy at cell membranes and in cytoplasm of B‐lymphoblasts. Laser irradiation of cells (532 nm, 10 nanoseconds, 0.6 J/cm2) induced microbubbles selectively in leukemia cells with large clusters, but not in cells with single NPs or small clusters. Quantitative analysis demonstrated that only 0.1%–1.5% of tumor cells and 77%–84% of normal bone marrow cells survived laser pulse.

Conclusions

Two‐stage cell targeting method permits formation of NP clusters selectively in diagnosis‐specific tumor cells. The clusters serve as effective sources of photothermally‐induced microbubbles, which kill individual target cells after a single laser pulse. The laser fluence threshold for generation of microbubbles is inversely proportional to the volume of NP clusters. Lasers Surg. Med. 38:631–642, 2006. © 2006 Wiley‐Liss, Inc.
Sperm incorporation and pronuclear development during fertilization in the freshwater bivalve Dreissena polymorpha
Authors: Misamore Michael J. , Stein Katheryn K. , Lynn John W.
Published: May 2006

The invasive zebra mussel, Dreissena polymorpha (D. polymorpha), is proving to be a valuable model for understanding general mechanisms of fertilization, particularly regarding sperm incorporation. In the present study, we tracked the various components of the fertilizing sperm of D. polymorpha during sperm incorporation. During fertilization the sperm membrane remains associated with the egg surface as a distinct patch that disperses over time. This patch marked the site of sperm entry that occurs predominately on the CD blastomere. Taking advantage of the relatively unpigmented cytoplasm, real‐time observations were made of the incorporated sperm nucleus as it decondensed and reformed as a developing pronucleus. Pronuclear enlargement occurred progressively and at rates comparable with previously reported fixed‐time point observations. Sperm mitochondria were incorporated and separated from the sperm along the leading edge of the decondensing nucleus. Sperm mitochondria labeled with Mitotracker Green® remained predominately associated with the CD blastomere following first cleavage and could be tracked to the 16‐cell stage before the fluorescence was too faint to detect. Additionally, the demembranated sperm axoneme was incorporated, separated during nuclear decondensation, and remained visible in the egg cytoplasm up to 30 min postinsemination (PI). The present study provides one of the most complete descriptions of incorporation on multiple sperm components into the egg and coordinates fixed‐time point observations with real‐time observations of sperm within the remarkably transparent egg cytoplasm of zebra mussels. Mol. Reprod. Dev. 1140–1148, 2006. © 2006 Wiley‐Liss, Inc.
Maternal housekeeping proteins translated during bovine oocyte maturation and early embryo development
Authors: Massicotte Lyne , Coenen Karine , Mourot Marina , Sirard Marc‐André
Published: May 2006

Protein synthesis from maternal mRNA is needed to sustain oocyte maturation and embryo development prior to the maternal‐embryonic transition (MET). Therefore, proteins that are expressed throughout this time are important and may be considered as maternal housekeeping proteins (MHKP). Our objectives were first, identify the translated protein patterns of bovine embryo development and secondly, determine the MHKP. Proteins synthesized during oocyte maturation and embryo development (2, 4 and 8‐cell stages) were labeled using [S35]‐Met and [S35]‐Cys, and visualized by 2‐DE. Embryos were cultured with α‐amanitine to inhibit new transcription. Only 46 proteins were present throughout all stages. Ten spots were identified by MALDI‐TOF and MS/MS: HSC71; HSP70; CypA; UCH‐L1; GSTM5; Cct5; E‐FABP; 2,3‐BPGM, ubiquitin‐conjugating enzyme E2D3; and β‐actin/γ‐actin. A new method called in silico protein identification confirmation was developed using EST databases. This method is a promising approach for use in rare tissue or from species with an incomplete protein database. This study has revealed that the translated protein patterns show a transition that brings the embryo to the MET. The needs in translated proteins between oocyte maturation and embryo development are different. In summary, this study represents the bases for future proteomics studies on bovine oocytes and embryos.
Prevention of dyskinesia by an NMDA receptor antagonist in MPTP monkeys: Effect on adenosine A2Areceptors
Authors: Morissette Marc , Dridi Mehdi , Calon Frédéric , Tahar Abdallah Hadj , Meltzer Leonard T. , Bédard Paul J. , Di Paolo Thérèse
Published: May 2006

Adenosine A2Areceptors (A2AR) have received increasing attention for the treatment ofL‐DOPA‐induced dyskinesias in Parkinson disease. In the present study, A2AR messenger RNA (mRNA) and receptor‐specific binding in the brain of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) monkeys were studied after treatment withL‐DOPA and a selective NR1A/2B NMDA receptor antagonist, CI‐1041. Four MPTP monkeys receivedL‐DOPA/benserazide and all developed dyskinesias, whereas among the four MPTP monkeys who additionally received CI‐1041, only one developed mild dyskinesias. Four normal monkeys and four MPTP‐treated monkeys were also studied. All MPTP monkeys had similar striatal dopamine (DA) denervation. A2AR mRNA levels, measured by in situ hybridization, were increased in the rostral lateral caudate and putamen of saline‐treated MPTP monkeys as well as in the caudal lateral and medial putamen when compared with those of controls. A2AR mRNA levels remained elevated in the rostral caudate and putamen ofL‐DOPA‐treated MPTP monkeys when compared with those of controls. A2AR mRNA levels ofL‐DOPA + CI‐1041‐treated monkeys were at control levels and decreased in the lateral rostral caudate and caudal putamen when compared with those ofL‐DOPA‐treated and saline‐treated MPTP monkeys respectively. No change was measured in the caudal medial putamen and caudate nucleus. A2ARs labeled by autoradiography with [3H]SCH‐58261 had lower level in theL‐DOPA + CI‐1041‐treated MPTP monkeys compared with saline‐ orL‐DOPA‐treated MPTP and control monkeys in the rostral lateral and medial caudate and the putamen. No effect of lesion orL‐DOPA treatment was measured on [3H]SCH‐58261‐specific binding. These findings suggest that blockade of NMDA receptors could prevent the development of dyskinesias by altering A2ARs. Synapse 60:239–250, 2006. © 2006 Wiley‐Liss, Inc.
Moderne Echokardiographie: Möglichkeiten und Grenzen
Authors: Zuber  , Erne
Published: May 2006

Die Echokardiographie hat die kardiale Abklärungsdiagnostik im nicht invasiven Bereich revolutioniert. Sie beinhaltet die zweidimensionale Abbildung des Herzens in bester räumlicher und zeitlicher Auflösung und durch Integration des Doppler auch eine hämodynamische Beurteilung. Neuste Sondentechnologie (Harmonic Imaging, Postprocessing), Kontrastechokardiographie und transösophageale Echokardiographie haben die Zahl an schlecht untersuchbaren Patienten stark reduziert. Die Stressechokardiographie hat sich bei der Ischämiediagnostik etabliert und die dreidimensionale Echokardiographie ist für den klinischen Einsatz bereit. Sie wird die Quantifizierung vorantreiben und die Messgenauigkeit noch verbessern. Die Anwendung dieser Technologien stellt aber hohe Ansprüche an den Ultraschallapparat und den Untersucher, sodass eine fundierte Aus-, Weiter-, und Fortbildung nach internationalen Guidelines wichtig ist.
Diagnostik depressiver Störungen im Alter
Authors: Beblo Thomas , Schrader Stephanie , Brand Christina
Published: May 2006

Zusammenfassung: Depressive Störungen bleiben häufig unentdeckt, obwohl sie zu den häufigsten psychischen Störungen gehören und bekannt ist, dass sich eine fehlende Behandlung negativ auf den Erkrankungsverlauf und die Entwicklung körperlicher Krankheiten auswirken kann. Aufgrund eines veränderten Symptomprofils und zusätzlicher differenzialdiagnostischer Fragestellungen, z. B. in der Abgrenzung zu demenziellen Erkrankungen, ergeben sich gerade bei älteren Patienten schwierige diagnostische Fragestellungen. Eine angemessene Diagnostik setzt zum einen den Einsatz kategorialer Untersuchungsverfahren voraus, die an den Klassifikationssystemen ICD-10 oder DSM-IV orientiert sind. Zur Einschätzung des Depressionsschweregrades und der Beurteilung von Krankheitsverläufen müssen zusätzlich Ratingskalen eingesetzt werden. Selbst- und Fremdratingverfahren ermöglichen dabei einen unterschiedlichen Zugang zur depressiven Symptomatik, weshalb beide Verfahrenstypen verwendet werden sollten. Da die meisten bekannten Verfahren nicht für die Diagnosestellung im höheren Lebensalter konstruiert wurden, erfordert der diagnostische Prozess einen feinfühligen, die Besonderheiten depressiver Störungen im Alter berücksichtigenden Umgang mit diesen Verfahren.
Leichte Kognitive Störung und Mild Cognitive Impairment
Authors: Reischies Friedel M. , Bürker Britta S.
Published: May 2006

Zusammenfassung: Die in der Frühphase einer Demenzentwicklung - beispielsweise der Alzheimer Demenz - auftretenden milden kognitiven Beeinträchtigungen stehen im Zentrum des Interesses verschiedener diagnostischer Konzepte der Leichten Kognitiven Störung. Diese Konzepte der Leichten Kognitiven Störung, z. B. Mild cognitive impairment und Ageing-associated cognitive decline, spielen im Hinblick auf die Suche nach Prädiktionsmöglichkeiten einer zukünftigen Demenzentwicklung sowie im Hinblick auf eine möglichst frühe Diagnose eines Demenzsyndroms vom Alzheimer Typ eine große Rolle. Die wesentlichen Konzepte werden ausführlich vorgestellt. Im Rahmen dieser Übersichtsarbeit wird 1. auf der Grundlage von pathophysiologischen Vorgänge im Verlauf einer Alzheimer Demenz sowie 2. aufgrund von Daten über die prädiktive Wertigkeit verschiedener neuropsychologischer Tests dargestellt, welche neuropsychologischen Tests in der Frühphase einer Demenzentwicklung zum Einsatz kommen können. Dies wird vor allem auch in dem Zusammenhang diskutiert, wie Alternsprozesse und deren Auswirkungen auf kognitive Leistungen die frühe Diagnose des Demenzsyndroms erschweren. Darüber hinaus wird erläutert, inwieweit Verlaufsuntersuchungen die Prädiktion bzw. die frühe Diagnose eines Demenzsyndroms ermöglichen können.
Selbstberichtete kognitive Funktions- fähigkeit und Lebensqualität
Authors: Bullinger Monika , Petersen Corinna , von den Driesch Volker , Daniel Dietmar , Irrgang Valeska , Ernen Carolin , Frölich Lutz
Published: May 2006

Zusammenfassung: Im Rahmen einer Anwendungsbeobachtung wurden 2001 Patienten mit leichten Hirnleistungsstörungen (MCI) vor und nach der Gabe von zwei pflanzlichen Präparaten (Tebonin(R) (Ginkgo-biloba-Extrakt (EGb 761(R)) und Neuroplant(R) (Hypericum-Extrakt WS 5572(R)) bezüglich ihrer Lebensqualität und selbstberichteten kognitiven Funktionsfähigkeit untersucht. Die Ergebnisse zeigen eine starke Beeinträchtigung der selbstberichteten Lebensqualität und kognitiven Kompetenz im Verhältnis zur Referenzpopulation in der Gruppe mit MCI und leichter Demenz zu Therapiebeginn und größere Beeinträchtigungen der Lebensqualität bei Patienten, die sowohl hinsichtlich kognitiver Defizite (erfasst über Mini Mental Status Test, MMST) als auch der Depressivität (erfasst über Geriatrische Depressions Skala, GDS) belastet sind. Unter Tebonin(R)- und Neuroplant(R)-Therapie verbessert sich die selbstberichtete Lebensqualität und kognitive Kompetenz signifikant, wobei die Änderungen bei den besonders beeinträchtigten Personen im GDS und MMST stark ausgeprägt sind. Selbstberichtete Lebensqualität und selbstberichtete kognitive Kompetenz korrelieren miteinander hoch und signifikant, und Veränderungen in der klinischen Symptomatik (gemessen über GDS und MMST) korrelieren mit der Veränderung in der Lebensqualität und kognitiven Kompetenz ebenfalls hoch und signifikant. Bei einer parallelisierten Gruppe von Patienten, die von den behandelnden Ärzte entweder der Neuroplant(R)- bzw. der Tebonin(R)-Gruppe zugewiesen worden waren, zeigten sich gleichförmige Verbesserungen bei beiden Therapieformen. Beeinträchtigungen von Lebensqualität und kognitiver Kompetenz sind bei Patienten mit leichten Hirnleistungsstörungen, abhängig vom Ausmaß der Beeinträchtigung, vorhanden. Nach Gabe von Tebonin(R) bzw. Neuroplant(R) zeigt sich eine Veränderung der Lebensqualität und der kognitiven Kompetenz, deren Rückführbarkeit auf die Medikation allerdings nicht hinreichend zu beurteilen ist, da es sich nicht um eine randomisierte klinische Studie handelt. Dennoch bestehen Hinweise darauf, dass sich die Lebensqualität und selbstberichtete kognitive Funktionsfähigkeit im Beobachtungszeitraum bessert.
Change in atmospheric mineral aerosols in response to climate: Last glacial period, preindustrial, modern, and doubled carbon dioxide climates
Authors: Mahowald Natalie M. , Muhs Daniel R. , Levis Samuel , Rasch Philip J. , Yoshioka Masaru , Zender Charles S. , Luo Chao
Published: May 2006

Desert dust simulations generated by the National Center for Atmospheric Research's Community Climate System Model for the current climate are shown to be consistent with present day satellite and deposition data. The response of the dust cycle to last glacial maximum, preindustrial, modern, and doubled‐carbon dioxide climates is analyzed. Only natural (non‐land use related) dust sources are included in this simulation. Similar to some previous studies, dust production mainly responds to changes in the source areas from vegetation changes, not from winds or soil moisture changes alone. This model simulates a +92%, +33%, and −60% change in dust loading for the last glacial maximum, preindustrial, and doubled‐carbon dioxide climate, respectively, when impacts of carbon dioxide fertilization on vegetation are included in the model. Terrestrial sediment records from the last glacial maximum compiled here indicate a large underestimate of deposition in continental regions, probably due to the lack of simulation of glaciogenic dust sources. In order to include the glaciogenic dust sources as a first approximation, we designate the location of these sources, and infer the size of the sources using an inversion method that best matches the available data. The inclusion of these inferred glaciogenic dust sources increases our dust flux in the last glacial maximum from 2.1 to 3.3 times current deposition.
Remote laser‐induced breakdown spectroscopy analyses of Dar al Gani 476 and Zagami Martian meteorites
Authors: Thompson J. R. , Wiens R. C. , Barefield J. E. , Vaniman D. T. , Newsom H. E. , Clegg S. M.
Published: May 2006

Laser‐induced breakdown spectroscopy (LIBS) was recently selected to provide active remote sensing compositional information on the Mars Science Laboratory (MSL) rover. The ability of LIBS to remotely determine differences between basaltic rock types on Mars is investigated by analyzing two Martian basaltic shergottite meteorites whose compositions differ slightly and which also differ slightly in texture. Using 14 analysis spots of ~400 µm diameter on Dar al Gani (DaG) 476 and 9 analysis spots on Zagami, the LIBS technique at a 5.4 m standoff distance clearly distinguished the olivine‐phyric (DaG 476) from the basaltic (Zagami) shergottite on the basis of MgO and CaO. Mean elemental abundances agreed with literature values for these meteorites to within ~12% for most of the major elements. The ability of LIBS to remotely distinguish between basaltic and andesitic compositions in a Martian environment was also investigated by analyzing a known andesite standard and comparing its spectra to the Martian basaltic shergottite spectra, yielding agreement with the literature andesite composition within 9%. The data presented here demonstrate the ability of LIBS to provide reasonable estimates of whole rock composition as well as determine relatively subtle differences in rock types from a distance.
Inflammatory Cell Infiltration after Endothelin-1-Induced Cerebral Ischemia: Histochemical and Myeloperoxidase Correlation with Temporal Changes in Brain Injury
Authors: Weston Robert M , Jones Nicole M , Jarrott Bevyn , Callaway Jennifer K
Published: May 2006

Accumulation of neutrophils in brain after transient focal stroke remains controversial with some studies showing neutrophils to be deleterious, whereas others suggest neutrophils do not contribute to ischemic injury. Myeloperoxidase (MPO) has been used extensively as a marker for quantifying neutrophil accumulation, but is an indirect method and does not detect neutrophils alone. To elucidate the interaction of macrophages in the neutrophil inflammatory response, we conducted double-label immunofluorescence in brain sections at 0, 1, 2, 3, 7, and 15 days after ischemia. Each of these results was obtained from the same animal to determine correlations between neutrophil infiltration and ischemic damage. It was found that MPO activity increased up to 3 days after cerebral ischemia. Dual-staining revealed that macrophages engulf neutrophils in the brain and that this engulfment of neutrophils increased with time, with 50% of neutrophils in the brain engulfed at 3 days and approximately 85% at 15 days ( N=5, P < 0.05). Interestingly, at 7 days the amount of dual-staining was decreased to 20% ( N=5, P < 0.05). Neutrophil infiltration was positively correlated with ischemic damage in both the cortex and striatum ( r2 = 0.86 and 0.80, respectively, P < 0.01). The results of this study indicate that the MPO from neutrophils phagocytized by macrophages may continue to contribute to the overall MPO activity, and that previous assessments that have utilized this marker to measure neutrophil accumulation may have miscalculated the number of neutrophils within the ischemic territory and hence their contribution to the evolution of the infarct at later time points. Thus any biphasic infiltration of neutrophils may have been masked by the accumulation of macrophages.
In vivo Quantification of Serotonin Transporters Using [11C]DASB and Positron Emission Tomography in Humans: Modeling Considerations
Authors: Ogden R Todd , Ojha Ashish , Erlandsson Kjell , Oquendo Maria A , Mann J John , Parsey Ramin V
Published: May 2006

Positron emission tomography (PET) studies of the serotonin transporter (5-HTT) in the human brain are increasingly using the radioligand [11C] N, N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine. A variety of models have been applied to such data in several published articles; however to date, these models have not been validated with test–retest data. We recruited 11 healthy subjects and conducted two identical scans on each subject on the same day. We considered four different models (one- and two-tissue compartment kinetic models, likelihood estimation in graphical analysis (LEGA; a bias-free alternative to the graphical method), and basis pursuit) along with fast noniterative approximations to the kinetic models. We considered four different outcome measures (total volume of distribution ( VT), binding potential with (BP) and without (BP1), free-fraction adjustment, and specific-to-nonspecific equilibrium partition coefficient (BP2)). To assess the performance of each model, we compared results using six different metrics (percent difference (PD) and within-subject mean sum of squares for reproducibility, interclass coefficient for reliability, variance across subjects, identifiability based on bootstrap resampling of residuals for each method, and time stability analysis to determine minimal required scanning time). We considered analysis of both at the voxel level and at the region of interest (ROI) level and compared results from these two approaches to assess agreement. We determined that 100 mins of scanning time is adequate and that for ROI-level analysis, LEGA gives best results. Average PD is 5.51 for VT, 20.7 for BP, 17.2 for BP1, and 16.5 for BP2 across all regions. For voxel-level analysis we determined that the one-tissue compartment noniterative model is best.
White Matter Injury Correlates with Hypertonia in an Animal Model of Cerebral Palsy
Authors: Drobyshevsky Alexander , Derrick Matthew , Wyrwicz Alice Mary , Ji Xinhai , Englof Ila , Ullman Lauren Marie , Zelaya Mario Enrique , Northington Frances Josephine , Tan Sidhartha
Published: May 2006

Hypertonia and postural deficits are observed in cerebral palsy and similar abnormalities are observed in postnatal rabbits after antenatal hypoxia–ischemia. To explain why some kits become hypertonic, we hypothesized that white matter injury was responsible for the hypertonia. We compared newborn kits at postnatal day 1 (P1) with and without hypertonia after in vivo global fetal hypoxia–ischemia in pregnant rabbits at 70% gestation. The aim was to examine white matter injury by diffusion tensor magnetic resonance imaging indices, including fractional anisotropy (FA). At P1, FA and area of white matter were significantly lower in corpus callosum, internal capsule, and corona radiata of the hypertonic kits ( n = 32) than that of controls ( n = 19) while nonhypertonic kits ( n = 20) were not different from controls. The decrease in FA correlated with decrease in area only in hypertonia. A threshold of FA combined with area identified only hypertonic kits. A reduction in volume and loss of phosphorylated neurofilaments in corpus callosum and internal capsule were observed on immunostaining. Concomitant hypertonia with ventriculomegaly resulted in a further decrease of FA from P1 to P5 while those without ventriculomegaly had a similar increase of FA as controls. Thus, hypertonia is associated with white matter injury, and a population of hypertonia can be identified by magnetic resonance imaging variables. The white matter injury manifests as a decrease in the number and density of fiber tracts causing the decrease in FA and volume. Furthermore, the dynamic response of FA may be a good indicator of the plasticity and repair of the postnatal developing brain.
Cerebral Vascular Mean Transit Time in Healthy Humans: A Comparative Study with PET and Dynamic Susceptibility Contrast-Enhanced MRI
Authors: Ibaraki Masanobu , Ito Hiroshi , Shimosegawa Eku , Toyoshima Hideto , Ishigame Keiichi , Takahashi Kazuhiro , Kanno Iwao , Miura Shuichi
Published: May 2006

Cerebral vascular mean transit time (MTT), defined as the ratio of cerebral blood volume to cerebral blood flow (CBV/CBF), is a valuable indicator of the cerebral circulation. Positron emission tomography (PET) and dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) are useful for the quantitative determination of MTT in the clinical setting. The aim of this study was to establish a normal value set of MTT as determined by PET and by DSC-MRI and to identify differences between these methods. Seven healthy volunteers were studied with 15O-PET (H215O and C15O) and gradient-echo echo-planar DSC-MRI at 1.5 T. In the DSC-MRI study with bolus injection of contrast agent, deconvolution analysis was performed. Comparison of gray-to-white matter ratios showed fairly good agreement between PET and DSC-MRI for all parameters (relative CBV, relative CBF, and relative MTT), confirming the validity of relative measurements with DSC-MRI. However, quantitative MTT measured by DSC-MRI was significantly shorter than that measured by PET in cerebral cortical regions (2.8 to 3.0 secs for DSC-MRI versus 3.9 to 4.3 secs for PET) and the centrum semiovale (3.5secs for DSC-MRI versus 4.8secs for PET). These discrepancies may be because of the differences in the intrinsic sensitivity of each imaging modality to vascular components; whereas PET measurement of CBV is equally sensitive to all vascular components, measurement with DSC-MRI originates from the microvasculature in the vicinity of the brain parenchyma. This underlying difference may influence interpretation of MTT determined by PET or by DSC-MRI for patients with cerebrovascular disease.
Gender-Specific Neuroprotection by 2-Iminobiotin after Hypoxia—Ischemia in the Neonatal Rat via a Nitric Oxide Independent Pathway
Authors: Nijboer Cora HA , Groenendaal Floris , Kavelaars Annemieke , Hagberg Henrik H , van Bel Frank , Heijnen Cobi J
Published: May 2006

We have shown earlier that 2-iminobiotin (2-IB) reduces hypoxia-ischemia (HI)-induced brain damage in neonatal rats, and presumed that inhibition of nitric oxide synthases (NOS) was the underlying mechanism. We now investigated the effect of 2-IB treatment in P7 rat pups to determine the role of gender and the neuroprotective mechanism. Pups were subjected to HI (occlusion of right carotid artery and 120 mins FiO2 0.08) and received subcutaneous (s.c.) 10 mg/kg 2-IB at 0, 12 and 24 h after hypoxia. After 6 weeks, neuronal damage was assessed histologically. We determined cerebral nitrite and nitrate (NOx) and nitrotyrosine, heat-shock protein 70, cytosolic cytochrome c, cleaved caspase 3, nuclear translocation of apoptosis-inducing factor (AIF) and the effect of 2-IB on NOS activity in cultured cells. 2-Iminobiotin treatment reduced long-term brain damage in female but not male rats. Unexpectedly, 2-IB treatment did not reduce cerebral NOx or nitrotyrosine levels, and did not inhibit NOS activity in vitro. The gender-dependent neuroprotective effect of 2-IB was reflected in inhibition of the HI-induced increase in cytosolic cytochrome c and cleaved caspase 3 in females only. Hypoxia–ischemia-induced activation of AIF was observed in males only and was not affected by 2-IB. Post-HI treatment with 2-IB provides gender-specific long- and short-term neuroprotection in female P7 rats via inhibition of the cytochrome c-caspase 3 neuronal death pathway. 2-Iminobiotin did not alter cerebral NOx nor inhibited NOS in intact cells. Therefore, we conclude that it is highly unlikely that the neuroprotective effect of 2-IB involves NOS inhibition.
The Mitochondrial KATPChannel Opener BMS-191095 Reduces Neuronal Damage after Transient Focal Cerebral Ischemia in Rats
Authors: Mayanagi Keita , Gáspár Tamás , Katakam Prasad VG , Kis Béla , Busija David W
Published: May 2006

Activation of mitochondrial ATP-sensitive potassium (mitoKATP) channels protects the brain against ischemic or chemical challenge. Unfortunately, the prototype mitoKATPchannel opener, diazoxide, has mitoKATPchannel-independent actions. We examined the effects of BMS-191095, a novel selective mitoKATPchannel opener, on transient ischemia induced by middle cerebral artery occlusion (MCAO) in rats. Male Wister rats were subjected to 90 mins of MCAO. BMS-191095 (25 μg; estimated brain concentration of 40 μmol/L) or vehicle was infused intraventricularly before the onset of ischemia. In addition, the effects of BMS-191095 on plasma and mitochondrial membrane potentials and reactive oxygen species (ROS) production in cultured neurons were examined. Finally, we determined the effects of BMS-191095 on cerebral blood flow (CBF) and potassium currents in cerebrovascular myocytes. Treatment with BMS-191095 24 h before the onset of ischemia reduced total infarct volume by 32% and cortical infarct volume by 38%. However, BMS-191095 administered 30 or 60 mins before MCAO had no effect. The protective effects of BMS-191095 were prevented by co-treatment with 5-hydroxydecanoate (5-HD), a mitoKATPchannel antagonist. In cultured neurons, BMS-191095 (40μmol/L) depolarized the mitochondria without affecting ROS levels, and this effect was inhibited by 5-HD. BMS-191095, similar to the vehicle, caused an unexplained but modest reduction in the CBF. Importantly, BMS-191095 did not affect either the potassium currents in cerebrovascular myocytes or the plasma membrane potential of neurons. Thus, BMS-191095 afforded protection against cerebral ischemia by delayed preconditioning via selective opening of mitoKATPchannels and without ROS generation.
Using a phase space statistic to identify resonant objects
Authors: Carroll Thomas L.
Published: May 2006

The identification of resonant objects in radar or sonar, important for object identification, is difficult because existing methods require that the signal have a large signal-to-noise ratio. It is shown in this article that a modified version of the Kaplan–Glass (KG) statistic, a phase space statistic used to determine if a signal is deterministic, is sensitive to the properties of resonant objects. The modified KG statistic can be used to detect the presence of a resonant object even when the radar or sonar signal does not come from a deterministic dynamical system. The use of the modified KG statistic both numerically and in a simple experiment is also demonstrated.
Exciton radiative lifetime in ZnO quantum dots embedded in SiOx matrix
Authors: Zhang X. H. , Chua S. J. , Yong A. M. , Chow S. Y. , Yang H. Y. , Lau S. P. , Yu S. F.
Published: May 2006

Using a simple process of the deposition of ZnO thin films on SiOx∕Si substrates and subsequent thermal annealing, we fabricated ZnO quantum dots embedded in silicon oxide matrix. The ZnO quantum dots were characterized using transmission electron microscopy, and time-integrated and time-resolved photoluminescences. We measured an exciton radiative lifetime of 65ps at 4.3K, which is much shorter than the exciton radiative lifetime of 322ps in bulk ZnO. The short exciton radiative lifetime can be explained in terms of exciton superradiance.