bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction Back to Nurture: Cross-Cultural Research as a Paradigm for Understanding Bio-Cultural Dynamics of Cognitive Ageing
Authors: Luszcz Mary
Published: September 2006

Background: One of the earliest and most persistent inquiries in developmental psychology is that of the relative contributions of nature and nurture to human ontogeny. One way of studying this distinction is by doing cross-cultural studies, in which culture provides a powerful way to operationalize the influence of nurture. Objective: The purpose is to provide some background to the emergence of the field of cross-cultural gerontological research, as a prelude to the special series of papers on cognitive ageing and culture from the laboratory of Park and Nisbett and their colleagues. Methods: A qualitative review of theoretical notions about cross-cultural differences provides an introduction and orientation to papers dealing with aspects of cognitive ageing, including picture naming specificity, source memory, use of categorical information in free recall, and perceptions of stereotypes of older and younger adults. Results: Most of the research on cognitive ageing has focused on Western cultures and has assumed universality in the operation of the cognitive system. If culture makes a difference, a plausible hypothesis might be that, with ageing, any effects of culture on cognitive processes would become more apparent, due to older adults’ increased exposure to their culture, and that these might be limited to the pragmatics of intelligence or crystallized abilities. The papers presented demonstrate that for some cognitive processes, i.e., source memory and free recall, cultural invariance, or universality of cognitive ageing, was observed. Further, stereotypes of both cultures shifted with advancing age from positive to increasingly negative views for mental and physical domains. A modest interaction of age and culture was observed in social and emotional domains, where stereotypes were relatively neutral, except for a small positive bias among the young Chinese participants for both older and younger adults. Marked cultural differences were seen in naming specificity and in the use of categories to structure the recall process. Conclusions: Claims have been made about universals of cognitive function, particularly for basic cognitive processes. These results challenge that view. Cross-cultural research has begun to reshape the way we think about cognitive ageing.
Source Memory, Aging and Culture
Authors: Chua Hannah Faye , Chen Wenfeng , Park Denise C.
Published: September 2006

Background: The present study investigates the possibility that culture affects age differences in context memory. There is evidence that East-Asians process scenes more holistically and show better context memory than Americans. Objective: We examined evidence for differences in binding source to context in young and old Americans and native Chinese. We hypothesized that age effects on source memory could be mitigated due to these cultural differences in processing style. Methods: During incidental encoding, younger and older Chinese and Americans watched a video with statements spoken by four distinct speakers. After a brief interval, participants identified source (experiment 1) or item and source (experiment 2). Results: We observed substantial age-related deficits in source memory in both cultures but little evidence for cultural differences in source or item memory. Conclusion: Basic source memory processes operate similarly across culture and age. The source of holistic processing differences observed between cultures may occur in cognitive operations that are more highly bound to a social context.
Categorical Organization in Free Recall across Culture and Age
Authors: Gutchess Angela H. , Yoon Carolyn , Luo Ting , Feinberg Fred , Hedden Trey , Jing Qicheng , Nisbett Richard E. , Park Denise C.
Published: September 2006

Background: Cross-cultural differences in cognition suggest that Westerners use categories more than Easterners, but these differences have only been investigated in young adults. Objective: The contributions of cognitive resource and the extent of cultural exposure are explored for free recall by investigating cross-cultural differences in categorical organization in younger and older adults. Cultural differences in the use of categories should be larger for elderly than young because categorization is a well-practiced strategy for Westerners, but age-related cognitive resource limitations may make the strategy difficult for elderly Easterners to implement. Therefore, we expect that cultural differences in categorization will be magnified in elderly adults relative to younger adults, with Americans categorizing more than Chinese. Methods: Across two studies, 112 young and 112 elderly drawn from two cultures (American and Chinese) encoded words presented in their native language. One word list contained categorically-unrelated words and the other, categorically-related words; both lists were presented in the participants’ native language. In experiment 1, the words were strong category associates, and in experiment 2, the words were weak category associates. Participants recalled all the words they could remember, and the number of words recalled and degree of clustering by category were analyzed. Results: As predicted, cultural differences emerged for the elderly, with East-Asians using categories less than Americans during recall of highly-associated category exemplars (experiment 1). For recall of low-associate exemplars, East-Asians overall categorized less than Americans (experiment 2). Surprisingly, these differences in the use of categories did not lead to cultural differences in the number of words recalled. The expected effects of age were apparent with elderly recalling less than young, but in contrast to previous studies, elderly also categorized less than young. Conclusion: These studies provide support for the notion that cultural differences in categorical organization are larger for elderly adults than young, although culture did not impact the amount recalled. These data suggest that culture and age interact to influence cognition.
Age-Related Stereotypes: A Comparison of American and Chinese Cultures
Authors: Boduroglu Aysecan , Yoon Carolyn , Luo Ting , Park Denise C.
Published: September 2006

Background: It is commonly assumed that age-related stereotypes are more positive in East Asian cultures compared to Western cultures. However, research conducted in Western cultures has demonstrated that age-related stereotypes are multidimensional and their valence is content-dependent. Objective: In this study we investigated stereotypes about young and old adults, held by both young and old in the US and in China by focusing on the valence of age stereotypes across two content domains: social/emotional and mental/physical. The goal was to identify whether there were any cultural differences in age-related stereotypes in Chinese and American cultures. Methods: Both young and old Chinese and American participants were asked to describe typical young and typical old people. All responses were then coded for valence (positive/negative/neutral) and for content (mental/physical, social/emotional, other). Descriptors about young and old people were initially analyzed separately; then data were integrated to examine group tendencies to be more positive or negative for each target age group. Results: In both cultures, stereotypes reflected a shift from more positive to increasingly negative views of mental and physical traits as a function of aging. In social and emotional domains, stereotypes regarding old and young adults were relatively neutral, except for a small positive bias found among the young Chinese adults for both target age groups. Conclusion: Our results indicate that age-related beliefs regarding typical older adults are similar across East-Asian and Western cultures and that a global positive bias for old age in East-Asia is absent.
FISH-mapping of LEP and SLC26A2 genes in sheep, goat and cattle R-banded chromosomes: comparison between bovine, ovine and caprine chromosome 4 (BTA4/OAR4/CHI4) and human chromosome 7 (HSA7)
Authors: Perucatti A. , Di Meo G.P. , Vallinoto M. , Kierstein G. , Schneider M.P.C. , Incarnato D. , Caputi Jambrenghi A. , Mohammadi G. , Vonghia G. , Silva A. , Brenig B. , Iannuzzi L.
Published: September 2006

Sheep (OAR), goat (CHI) and cattle (BTA) R-banded chromosome preparations, obtained from synchronized cell cultures, were used to FISH-map leptin (LEP) and solute carrier family 26 member 2 (SLC26A2) genes on single chromosome bands. LEP maps on OAR4q32 and CHI4q32, being the first assignment of this gene to these two species. SLC26A2 maps on BTA7q24, OAR5q24 and CHI7q24. This gene, too, was assigned for the fist time to both sheep and goat chromosomes, while it was more precisely localized on a single chromosome band in cattle. Improved cytogenetic maps of BTA4/OAR4/CHI4 were constructed and compared with HSA7 revealing five main conserved segments and complex chromosome rearrangements, including a centromere repositioning, differentiating HSA7 and BTA4/OAR4/CHI4.
Chromosomal alterations in 98 endometrioid adenocarcinomas analyzed with comparative genomic hybridization
Authors: Levan K. , Partheen K. , Österberg L. , Helou K. , Horvath G.
Published: September 2006

The aim of the present study was to investigate chromosomal alterations in a large set of homogeneous tumors, 98 endometrioid adenocarcinomas. We also wanted to evaluate differences in chromosomal alterations in the different groups of tumors in relation to stage, survival and invasive or metastatic properties of the tumors. Comparative genomic hybridization (CGH) was used to detect chromosomal alterations in tissue samples from 98 endometrioid adenocarcinomas. All chromosomes were involved in DNA copy number variations at least once in the tumor material, but certain changes were recurrent and rather specific. Among the specific changes, it was possible to identify 39 chromosomal regions displaying frequent DNA copy number alterations. The most frequent alteration was detected at 1q25→q42, in which gains were found in 30 cases (30%). Gains at 19pter→p13.1 were detected in 26 tumors (26%) and at 19q13.1→q13.3 in 19 tumors (19%). Increased copy numbers were also detected at 8q (8q21→q22 and 8q22→qter), at a relatively high rate, in 17 cases (17%). Furthermore, gains at 10q21→q23 and 10p were found in 14 (14%) and 13 cases (13%), respectively. The most common losses were found in the three regions 4q22→qter, 16q21→qter and 18q21→qter, all of which were detected in eight of the 98 tumors (8%). We also detected differences between the tumors from deceased patients and from survivors. Gain at 1q25→q42 was more commonly detected in the tumors from patients who died of cancer. We noted that the regions most affected differed in the different surgical stages (I–IV). The results of the CGH analysis identify specific chromosomal regions affected by copy number changes, appropriate objects for further genetic studies.
Genomic organization and expression pattern of scapinin (PHACTR3) in mouse and human
Authors: Worch S. , Fiedler E. , Hansmann I. , Schlote D.
Published: September 2006

Scapinin has been found to bind to cytoplasmic actin and is also a putative regulatory subunit of protein phosphatase-1 (PP1). It is found attached to the nuclear matrix-intermediate filament (NM-IF) and is down-regulated by differentiation of tumor cells. We have analyzed the genomic structure and tissue-specific expression pattern of both the human scapinin gene (PHACTR3) and the orthologous mouse gene. Both genes showed a highly conserved complex genomic organization with four different leader exons. Alternative splicing of exon 5 was found to be limited to human and variable polyadenylation in mouse transcripts only. In both species expression seems to occur predominantly in the brain. By Northern blot analysis two major transcripts in human and three transcripts in mouse were detected. Expression analysis in the mouse revealed a tissue-specific complex transcription pattern in the brain and a specific pattern was observed during prenatal development. Based on the transcriptional data we therefore assume scapinin to have a distinct biological function in the mammalian brain.
Atypical mutational properties of human chromosome 21 suggested by comparative genome-scale analyses
Authors: Vieira A.
Published: September 2006

Mutation of genetic material is a necessary component of evolutionary change. There is evidence for both intragenome and intergenome heterogeneity in terms of mutation frequencies. Reported comparisons of DNA sequence differences between human and chimpanzee (Pan troglodytes) suggest that human chromosome 21 may exhibit mutational hypervariability relative to the other autosomes. In the present study, further evidence is provided for such hypervariability based on large-scale analyses of amino acid composition of (translated) human genes and pseudogenes. A comparison of the variation in the above cases (i.e., DNA sequence differences and amino acid composition differences) yields similar ratios (1.2–1.4) for chromosome 21 relative to the other autosomes, e.g., human chromosome 22 – an autosome that is more typical in this respect and is of similar size to 21. Human chromosome 21 is also presented in this study as being atypical in terms of reported associations between mutation rates and GC content or CpG dinucleotides. In terms of GC distribution patterns, a comparison of NT_011512 and NT_011520 contigs revealed a lower heterogeneity for human chromosome 21 relative to 22. Possible hypermutability of chromosome 21 is further discussed in the context of GC patterns, reported long interspersed nuclear element content (LINE1s), and the implications of these parameters for chromatin structure.
The role of caspases in photoreceptor cell death of the retinoschisin-deficient mouse
Authors: Gehrig A. , Janssen A. , Horling F. , Grimm C. , Weber B.H.F.
Published: September 2006

Early schisis cavities in the retinal bipolar cell layer accompanied by progressive loss of cone and rod photoreceptor cells are the hallmark of the retinoschisin-deficient (Rs1h–/Y) murine retina. With this study we aimed at elucidating the molecular events underlying the photoreceptor cell death in this established murine model of X-linked juvenile retinoschisis. We show that photoreceptor degeneration in the Rs1h–/Y mouse is due to apoptotic events peaking around postnatal day 18. Cell death is accompanied by increased expression of initiator and inflammatory caspases but not by downstream effector caspases. The strong induction of caspase-1 (Casp1) prompted us to explore its involvement in the apoptotic process. We therefore generated double knock-out mice deficient for both retinoschisin and Casp1. No direct influence of the Casp1 genotype on apoptosis could be identified although striking differences in the overall number of resident microglia were observed independent of the Rs1h genotype.
Characterization of two whey protein genes in the Australian dasyurid marsupial, the stripe-faced dunnart (Sminthopsis macroura)
Authors: De Leo A.A. , Lefevre C. , Topcic D. , Pharo E. , Cheng J.F. , Frappell P. , Westerman M. , Graves J.A.M. , Nicholas K.R.
Published: September 2006

We report the first isolation and sequencing of genomic BAC clones containing the marsupial milk protein genes Whey Acidic Protein (WAP) and Early Lactation Protein (ELP). The stripe-faced dunnart WAPgene sequence contained five exons, the middle three of which code for the WAPmotifs and four disulphide core domains which characterize WAP. The dunnart ELPgene sequence contained three exons encoding a protein with a Kunitz motif common to serine protease inhibitors. Fluorescence in situ hybridization located the WAPgene to chromosome 1p in the stripe-faced dunnart, and the ELPgene to 2q. Northern blot analysis of lactating mammary tissue of the closely related fat-tailed dunnart has shown asynchronous expression of these milk protein genes. ELPwas expressed at only the earlier phase of lactation and WAPonly at the later phase of lactation, in contrast to β-lactoglobulin (BLG) and α-lactalbumin (ALA) genes, which were expressed in both phases of lactation. This asynchronous expression during the lactation cycle in the fat-tailed dunnart is similar to other marsupials and it probably represents a pattern that is ancestral to Australian marsupials.
Karyotype differentiation in Chromaphyosemion killifishes (Cyprinodontiformes, Nothobranchiidae). II: Cytogenetic and mitochondrial DNA analyses demonstrate karyotype differentiation and its evolutionary direction in C. riggenbachi
Authors: Völker M. , Sonnenberg R. , Ráb P. , Kullmann H.
Published: September 2006

African killifishes of the genus Chromaphyosemion show a high degree of phenotypic and karyotypic diversity. The latter is especially pronounced in C. riggenbachi, a morphologically defined species restricted to a small distribution area in Cameroon. This study presents a detailed reconstruction of karyotype differentiation within C. riggenbachi using conventional Giemsa staining and sequential chromosome banding as well as a phylogenetic analysis based on part of the mitochondrial (mt) cytochrome b gene from eleven populations. The cytogenetic analysis revealed differences in chromosome morphology, banding patterns and/or diploid chromosome number (2n) among all populations examined. Diploid number ranged from 2n = 20 to 2n = 36 and varied mainly among populations, while C-banding patterns and NOR phenotypes showed fixed differences among populations as well as some variability within populations. The mtDNA analysis disclosed five clearly differentiated haplotype groups. Mapping the karyotype data onto the mtDNA dendrogram revealed a decrease in 2n from the most basal to the most derived groups, thus demonstrating a reduction of 2n during their evolutionary history. Our results indicate that karyotype differentiation involved Robertsonian fusions as well as non-Robertsonian processes. Causes of the high karyotypic variability may include an elevated chromosomal mutation rate as well as certain features of the ecology and mating system that could facilitate the fixation of chromosomal rearrangements. The pattern of karyotype and haplotype differentiation and the results of previous crossing experiments suggest incipient speciation in C. riggenbachi.
Characterization of a de novo complex chromosome rearrangement (CCR) involving chromosomes 2 and 12, associated with mental retardation and impaired speech development
Authors: Schwarzbraun T. , Ullmann R. , Schubert M. , Ledinegg M. , Ofner L. , Windpassinger C. , Wagner K. , Kroisel P.M. , Petek E.
Published: September 2006

We report on a currently six-year-old patient with a de novo complex chromosome rearrangement (CCR) involving chromosomes 2 and 12. A translocation 2;12 that appeared to be reciprocal after standard banding turned out to be a complex event with seven breaks after molecular cytogenetic analyses. Array CGH analysis showed no imbalances at the breakpoints but revealed an additional microdeletion of about 80 kb on chromosome 11. The same deletion was also present in the phenotypically normal father. The patient showed relatively mild mental retardation, defined mainly as impaired speech development (orofacial dyspraxia) and psychomotor retardation. In addition, mild dysmorphic facial features like hypertelorism, a prominent philtrum and down-turned corners of the mouth were observed. We narrowed down all breakpoint regions to about 100 kb, using a panel of mapped bacterial artificial chromosome (BAC) clones for fluorescence in situ hybridization (FISH). BACs spanning or flanking all seven breakpoints were identified and no chromosomal imbalances were found consistent with the array CGH results. Our investigations resulted in the following karyotype: 46,XY,t(2;12)(2pter→2p25.3::2p23.3→2p25.2::2p23.3→2p14::2q14.3→2p14::2q14.3→2q14.3::12q 12→12qter;12pter→12q12::2p25.3→2p25.2::2q14.3→2qter).
The Lumbar Interspinous Ligaments in Humans: Anatomical Study and Review of the Literature
Authors: Scapinelli Raffaele , Stecco Carla , Pozzuoli Assunta , Porzionato Andrea , Macchi Veronica , De Caro Raffaele
Published: September 2006

In textbooks of human anatomy and atlases of spinal surgery, the lumbar interspinous ligaments are described and illustrated in various and often conflicting ways. Thirty-four lumbar vertebral columns (19 males, 15 females, range 17–92 years old), sampled at autopsy, were studied by dissection and macroscopic analysis. The orientation of the fibre bundles was evaluated in the sagittal plane by tracing a reference line parallel to the cranial border of the spinous process, and the degree of bundle tilting with reference to this line was measured in the ventral, middle and dorsal parts of the ligament. Histological and immunohistochemical (anti-S100) studies of the ligaments, on sagittal, frontal, and transversal planes, were also carried out. In vivo radiological validation was performed in 25 patients by MR and CT imaging. Macroscopically, the interspinous ligaments are consistently composed of bundles of fibres arranged in a characteristic pattern. Together, they present an oblique orientation from anterior to posterior in a caudal-cranial direction. In their ventral part the bundles form a slight curve with a posterior-inferior concavity. In the middle part, the bundles are thicker and arranged in an italic S shape with a mean degree of tilting of 52 ± 14, 21 ± 12 and 50 ± 17 in the anterior, intermediate and posterior subzones of the L2–L3 ligaments and of 32 ± 14, 11 ± 9 and 18 ± 11 in the anterior, intermediate and posterior subzones of the L4–L5 level. The dorsal part consists of obliquely ascending bundles of fibres mostly converging in the supraspinous ligament. Histologically, these ligaments are mainly composed of collagen fibres, whereas the elastic fibres are ubiquitous, although mostly concentrated in the ventral part, which is closely linked to the yellow ligament. The interspinous ligament is well supplied by small blood vessels and sensory nerves, the latter particularly in its dorsal part and on its lateral surfaces. According to collected data, the structure of the interspinous ligaments reflects their function, i.e., the italic S-shaped course of the fibrous bundles represents an available reserve of length in a poorly elastic ligament.
Reference Models for Mitral Valve Tissue Engineering Based on Valve Cell Phenotype and Extracellular Matrix Analysis
Authors: Flanagan T.C. , Black A. , O’Brien M. , Smith T.J. , Pandit A.S.
Published: September 2006

The advance of mitral valve repair techniques through tissue engineering is impeded by the lack of information regarding the cellular and extracellular components of the mitral valve. The present study aims to expand our understanding of the mitral valve structure by analysing the synthesis of extracellular matrix (ECM) proteins and the expression of nitric oxide synthase (NOS). Valvular endothelial cells (VECs) and valvular interstitial cells (VICs) were isolated from porcine mitral valves. Immunochemical staining of ECM components, including type I, II, III, IV and V collagen, laminin, fibronectin, elastin and chondroitin sulphate (CS), was performed on both mitral valve tissue and cell cultures. Reverse transcription polymerase chain reaction and immunochemistry were used to analyse NOS expression in native valve and in culture. Both VECs and VICs synthesised the basement membrane components, laminin and type IV collagen both in vivo and in vitro, amongst other fibrous ECM proteins. Synthesis of type I collagen and CS was absent in VEC cultures. Each cell type had a characteristic profile of NOS expression. VECs synthesised endothelial NOS both in vivo and in vitro, with a minority of VICs expressing neuronal NOS in vitro. The present study reports newly recognised aspects of the mitral valve structure and the in vitro behaviour of mitral valve cell populations based on ECM synthesis and NOS expression. The presented profiles can be used as base tools for the generation of data necessary for the selection of ideal cell sources and for the design of appropriate scaffolds for the development of effective tissue-engineered mitral valves.
Gene Expression Profiling of Mouse Embryonic Stem Cell Progeny Differentiated by Lumelsky’s Protocol
Authors: Kitano Mami , Kakinuma Michiru , Takatori Atsushi , Negishi Takayuki , Ishii Yoshiyuki , Kyuwa Shigeru , Yoshikawa Yasuhiro
Published: September 2006

Successful conversion of embryonic stem (ES) cells into insulin-producing cells has been reported by Lumelsky et al. (Science 2001;292:1389–1394); however, it remains controversial. In this study, we investigated the properties of ES cell progeny-induced differentiation according to Lumelsky’s protocol by immunocytochemistry, oligonucleotide microarray and real-time RT-PCR. Insulin-positive cells were observed at stages 3, 4 and 5. Microarray analysis demonstrated upregulation and appearance of some genes involved in pancreatic development but not β-cell-specific functional genes in cells at stage 5. Similarly, real-time RT-PCR revealed that expression of β-cell-specific functional genes such as islet amyloid polypeptide, insulin I and II was not increased in cells at stage 5. These results suggest that terminal differentiation of ES cell progeny toward functional pancreatic β-cell is insufficient. This study also demonstrates the usefulness of multiple time-course expression profiles for validating differentiation fates of ES cell progeny.
Cryopreservation of Osteoblast-Like Cells: Viability and Differentiation with Replacement of Fetal Bovine Serum in vitro
Authors: Reuther Tobias , Kettmann Corinna , Scheer Martin , Kochel Michael , Iida Seiji , Kübler Alexander C.
Published: September 2006

In reconstructive medicine, the clinical use of cryopreservation techniques depends on the absence of infectious agents such as prions. Therefore, we investigated the viability and differentiation of human osteoblast-like cells during replacement of fetal bovine serum in vitro. The aim of the present study is to replace the potentially infectious supplement fetal bovine serum during the cryopreservation procedure in order to perform future clinical trials. We used a cryopreservation technique with Me2SO for human osteoblast-like cells of iliac cancellous bone. In the cell culture of cryopreserved and fresh osteoblast-like cells, we substituted Dulbecco’s modification of Eagle’s medium (DMEM)/Ham’s F12 plus 1% penicillin/streptomycin with autologous serum, human serum albumin and Biseko® for fetal bovine serum. For the fourth treatment group, we removed fetal bovine serum without replacing it. DMEM/Ham’s F12 plus 1% penicillin/streptomycin with fetal bovine serum served as the control group. After 4, 7, 14 and 21 days of culture for the cryopreserved and noncryopreserved cells, we performed cell counting, a WST-1 test, ELISA for collagen type I, and osteocalcin. The activity of alkaline phosphatase was also measured. The best results were obtained for the group with autologous serum as a supplement after thawing, exceeding the other groups with regard to proliferation rate. Most viable cells were observed with no replacement before freezing and after thawing of the cells. With regard to differentiation, the cultures with autologous serum after thawing of the cells showed little concentration of the differentiation markers, probably due to early contact inhibition of the cells in vitro. With regard to effort and outcome, the most promising group for cryopreservation was the one with DMEM/Ham’s F12 plus 1% penicillin/streptomycin alone before freezing, especially when osteoblast-like cells were cultured in medium with autologous serum after thawing. This is important, as this in vitro setting resembles the in vivo situation when cryopreserved bone is transplanted. These findings indicate that, for clinical purposes, fetal bovine serum can be removed for cryopreservation of iliac cancellous bone with minor loss of viability.
Zona Pellucida Domain of ZPB1 Controls Specific Binding of ZPB1 and ZPC in Japanese Quail (Coturnix japonica)
Authors: Sasanami Tomohiro , Ohtsuki Mamoru , Ishiguro Tsukasa , Matsushima Kayoko , Hiyama Gen , Kansaku Norio , Doi Yukio , Mori Makoto
Published: September 2006

The extracellular matrix surrounding avian oocytes, referred to as the perivitelline membrane (PL), exhibits a three-dimensional network of fibrils between granulosa cells and the oocyte. We previously reported that one of its components, ZPC, is synthesized in granulosa cells that are specifically incorporated into the PL; this incorporation might be mediated by a specific interaction with ZPB1, another PL constituent, which is synthesized in the liver. In order to extend our previous findings, we established an expression system for quail ZPB1 using a mammalian cell line, and several ZPB1 mutants lacking the zona pellucida (ZP) domain or the glutamine-rich repeat region were produced. Western blot analysis of the immunoprecipitated materials with anti-ZPC antiserum indicated that ZPB1 was coimmunoprecipitated with the antiserum in the presence of ZPC. Ligand blotting also revealed the specific binding of ZPC and ZPB1 and indicated that the binding of these two components might be mediated via an ionic interaction. An analysis using recombinant ZPB1 demonstrated that the ZPB1 lacking the ZP domain did not bind to ZPC, whereas the mutant missing the glutamine-rich repeat region retained its capacity for binding. Furthermore, although the ZPB1 lacking the N-terminal half of the ZP domain was able to bind to ZPC, the deletion of the C-terminal half completely abolished ZPB1 binding to ZPC. These results suggested that the C-terminal half of the ZP domain of ZPB1 contains a binding site for ZPC, and that it appears to be involved in insoluble PL fibril formation in the quail ovary.
Roller Culture of Free-Floating Retinal Slices: A New System of Organotypic Cultures of Adult Rat Retina
Authors: Rzeczinski Stefan , Victorov Ilya V. , Lyjin Anatolij A. , Aleksandrova Olga P. , Harms Christoph , Kronenberg Golo , Freyer Dorette , Scheibe Franziska , Priller Josef , Endres Matthias , Dirnagl Ulrich
Published: September 2006

No experimental system exists to date for the in vitro study of retinal ganglion cell populations in a three-dimensional organotypic tissue environment. Here, we describe such a novel method for roller cultivation of adult retinas. Retinas of adult (1–3 months old) rats were cut into rectangular slices of approximately 1 mm2. Free-floating slices were cultured on a horizontal rotating roller drum (50–60 rpm) in a dry incubator at 36.5°C. During the first days of cultivation, primary flat retinal slices changed their configuration and transformed into ball-shaped tissue spheres (retinal bodies). Histological and immunocytochemical studies showed that the outer wall of the retinal bodies was formed by cell and fibre layers typical of mature retina with photoreceptors located on the outside. Initially, retinal bodies contained an inner cavity which later was completely obliterated and filled with glial cells, sprouting nerve fibres, and vascular structures. This culture system was further developed into a robust model of glutamate-induced neurotoxicity. Using a novel culture method of adult rat retina, preservation of the three-dimensional organotypic retinal cytoarchitecture was achieved, including survival of neurons in the ganglion cell layer and sprouting of nerve fibres of the axotomized retinal ganglion cells. This novel culture model promises to facilitate studies of retinal physiology and pathology.
Effect of Topical Nipradilol on Retinal Microvascular Leukocyte Adhesion in Diabetic Rats
Authors: Ono Ryuichiro , Kakehashi Akihiro , Ito Yuka , Sugi Norito , Makino Shinji , Kobayashi Eiji , Hakamada Yoji , Takagi Yasuhiro , Kitazume Yusuke , Kawakami Masanobu
Published: September 2006

Background: Retinal leukostasis plays an important role in the pathogenesis of diabetic retinopathy. Objectives: We studied the effects of nipradilol, a topical antiglaucoma αβ-blocker and nitric oxide donor, on the retinal vascular leukocyte adhesion of rats with diabetes. Methods: Diabetes was induced in seven Brown-Norway rats by one intravenous injection (65 mg/kg) of streptozotocin and confirmed by blood glucose levels >350 mg/dl 48 h after the injection. Nipradilol solution was instilled in the right eye and nipradilol-free base solution in the left eye for 3 weeks, after which the retinal microcirculation was evaluated by acridine orange leukocyte digital fluorography using laser scanning ophthalmoscopy. Leukocytes trapped in the retina were counted around the optic disc in a 5-disc-diameter area and compared between the right and the left eye. Results: The mean retinal leukostasis count in the nipradilol-treated eyes (19 ± 15 cells) was significantly lower than in the untreated eyes (49 ± 19 cells; p < 0.0008). The diameter of the retinal artery in the eyes treated with nipradilol significantly increased (111 ± 13.5%) compared with untreated eyes (p < 0.03). Conclusions: Topical nipradilol significantly reduced retinal leukostasis in the retinal microcirculation in diabetic rats and may be a prophylactic agent for early diabetic retinopathy through its nitric oxide donor effects on the microcirculation.
Nasolacrimal Endometriosis
Authors: Oner Ayse , Karakucuk Sarper , Serin Serdar
Published: September 2006

Endometriosis is the presence of endometrial tissue outside of the uterine cavity. In this paper, we present a patient with nasolacrimal system endometriosis which is a rare clinical condition.
Unexpected Peripheral Markers of Thyroid Function in a Patient with a Novel Mutation of the MCT8 Thyroid Hormone Transporter Gene
Authors: Herzovich V. , Vaiani E. , Marino R. , Dratler G. , Lazzati J.M. , Tilitzky S. , Ramirez P. , Iorcansky S. , Rivarola M.A. , Belgorosky A.
Published: September 2006

The specific thyroid hormone transporter, MCT8, located on the X chromosome, has led to the identification a novel syndrome. The objective is to relate phenotype with several tissue-specific thyroid functions. A 1-year-old boy, who had severe psychological damage and low serum T4, had received l-T4 for 3 months. At admission, body length was normal but weight was low. Off therapy, serum TSH was mildly elevated, serum T4 and free T4 were low, and serum T3 and free T3 were high. Direct sequencing of the MCT8 gene revealed a single nucleotide change that resulted in a novel nonsense mutation at codon 261 (Q261X) in exon 3. Since serum T3 was high, peripheral markers of hyperthyroidism were looked for. Bone age was advanced, despite the presence of malnutrition and low T4. Serum SHBG, a marker of thyroid hormone action in liver, was markedly elevated. Markers of skeletal muscle catabolism, ammonemia and lactic acid, were found to be elevated. The phenotype of MCT 8 mutation might be explained by differences in the entry of thyroid hormones into different cells. In the presence of an inactive MCT8 transporter, the high blood T3 levels might not be enough to prevent brain damage early in life, while they seem to be able to induce a postnatal state of peripheral hyperthyroidism in other tissues, such as liver, bone and skeletal muscle.
An Inhibin B and Estrogen-Secreting Adrenocortical Carcinoma Leading to Selective FSH Suppression
Authors: Barisson Villares Fragoso Maria Candida , Fonte Kohek Maria Beatriz , Matsunaga Martin Regina , Latronico Ana Claudia , Lucon Antonio Marmo , Zerbini Maria Claudia , Longui Carlos Alberto , Mendonca Berenice Bilharinho , Domenice Sorahia
Published: September 2006

Objective: Hormone-secreting adrenocortical tumors are frequently associated with endocrine syndromes. We describe a 30-year-old man who had abdominal pain, a nodule in the right breast and loss of libido. Abdominal magnetic resonance imaging revealed a very large tumor in the right adrenal gland. Methods: Hormonal profile disclosed increased levels of estradiol and slightly low testosterone levels. The basal and stimulated LH levels were normal, whereas basal and stimulated FSH levels were totally suppressed. Cortisol and adrenal androgen levels were normal. The unusual finding of selective FSH suppression suggested secretion of inhibin B by the adrenocortical tumor. A very high level of serum inhibin B (405 pg/ml) was demonstrated by ELISA assay. Right adrenalectomy and nephrectomy were performed and the tumor was classified as a malignant tumor (Weiss score: 7.0) and unilateral mastectomy disclosed a lipoma. Results: One week after surgery, a GnRH-stimulation test disclosed normal basal and stimulated FSH levels and low levels of inhibin B and estradiol. Immunohistochemical analysis with anti-B-inhibin antibody revealed intense staining in the adrenocortical tumor cells. One month after surgery, an abdominal magnetic resonance imaging revealed a local recurrence of the tumor and a second surgery was performed with partial resection of the tumor and the patient died 1 year after the first surgery. Conclusion: We herein report the first inhibin B and estradiol-secreting adrenocortical carcinoma. The unusual selective inhibition of FSH secretion should be considered a valuable hormonal finding for the diagnosis of inhibin B-secreting adrenocortical tumors.
NPC1L1: Evolution From Pharmacological Target to Physiological Sterol Transporter
Authors: Huff Murray W. , Pollex Rebecca L. , Hegele Robert A.
Published: September 2006

Niemann-Pick C1-like 1 protein (NPC1L1) was recently shown to be the molecular target of the cholesterol absorption inhibitor class of drugs, of which ezetimibe is the first widely used member. Since its discovery, NPC1L1 has also been shown to play a focal physiological role in intestinal absorption of sterols, including plant sterols and cholesterol. Evidence in support of this new metabolic pathway has been garnered not only through human, animal, and cell studies of function but also through the use of human genetics as an approach to study the association ofNPC1L1sequence variation with metabolic and drug-response phenotypes. The example of NPC1L1 shows how the elucidation of a pharmacological target can serve as a means to gain understanding of a key physiological pathway.
Conjugated Equine Estrogen, Esterified Estrogen, Prothrombotic Variants, and the Risk of Venous Thrombosis in Postmenopausal Women
Authors: Smith Nicholas L. , Heckbert Susan R. , Lemaitre Rozenn N. , Reiner Alexander P. , Lumley Thomas , Rosendaal Frits R. , Psaty Bruce M.
Published: September 2006

Background—

Joint exposure to oral conjugated equine estrogen (CEE) and prothrombotic genetic variants factor II G20210A or factor V G1601A (Leiden) increase venous thrombotic risk 6- to 16-fold in postmenopausal women. Esterified estrogen (EE), an alternative estrogenic compound, appears not to be associated with increased risk and nothing is known about the joint risk with prothrombotic genetic variants.

Methods and Results—

We conducted a population-based, case-control study among postmenopausal women within a health maintenance organization. Subjects included 328 cases who sustained a first venous thrombosis and 1591 controls. Current hormone use was defined using electronic pharmacy records and variants FII G20210A and FV Leiden were genotyped using blood samples. FII and FV Leiden variants were associated with 2.1-fold and 3.7-fold increases in venous thrombotic risk, respectively. Overall, CEE use was associated with a 2.5-fold increase in risk compared with no hormone use, whereas EE use was not associated with a statistically increased risk. Compared with no hormone use and no variant, joint exposure to CEE and either prothrombotic variant was associated with an odds ratio (OR) of 9.1 (95% CI: 4.5 to 18.2), whereas joint exposure to EE and either variant was associated with an OR of 2.1 (0.6 to 6.8). When analyses were restricted to hormone users with either variant, CEE use was associated with an OR of 5.3 (1.3 to 21.7) compared with EE use.

Conclusions—

These findings need replication and suggest EE use is associated with less risk than CEE use especially among 5% to 10% of women who are carriers of a prothrombotic variant.
Matrix Gla Protein Is Associated With Risk Factors for Atherosclerosis but not With Coronary Artery Calcification
Authors: O’Donnell Christopher J. , Shea M. Kyla , Price Paul A. , Gagnon David R. , Wilson Peter W. F. , Larson Martin G. , Kiel Douglas P. , Hoffmann Udo , Ferencik Maros , Clouse Melvin E. , Williamson Matthew K. , Cupples L. Adrienne , Dawson-Hughes Bess , Booth Sarah L.
Published: September 2006

Objectives—

Atherosclerotic coronary artery calcification (CAC) is associated with increased coronary heart disease (CHD) risk. Matrix Gla protein (MGP) is an inhibitor of calcification in vivo. However, little is known regarding the distribution of circulating MGP and its associations with CHD risk factors or with CAC in humans.

Methods and Results—

Serum MGP concentrations were determined in 2 independent populations of men and women free of clinically apparent cardiovascular disease: study A, n=316, mean age 58 years, and study B, n=452, mean age 68 years. CAC was determined by computed tomography. Mean MGP concentrations were 98.4 and 198 ng/mL in men, and 97.4 and 201 ng/mL in women, in study A and study B, respectively. In both cohorts, MGP levels were higher with increasing age. In age-adjusted analyses, there was an association of circulating MGP with increasing Framingham CHD risk score (in study A,
P
=0.003 in men and
P
=0.016 in women, respectively; in study B, a nonsignificant increase in men and
P
=0.05 in women, respectively). Significant associations of circulating MGP with high-density lipoprotein and other individual CHD risk factors were also noted in both cohorts. There were no consistent associations between MGP and CAC after adjustment for CHD risk score in the 2 cohorts.

Conclusions—

MGP is associated with individual CHD risk factors and the Framingham CHD risk score in men and women free of clinically apparent CHD. The relation of MGP with CAC deserves further study in larger populations.
Low-Density Lipoprotein Modified by Macrophage-Derived Lysosomal Hydrolases Induces Expression and Secretion of IL-8 Via p38 MAPK and NF-κB by Human Monocyte-Derived Macrophages
Authors: Hakala Jukka K. , Lindstedt Ken A. , Kovanen Petri T. , Pentikäinen Markku O.
Published: September 2006

Objective—Modified lipoproteins induce inflammatory reactions in the atherosclerotic arterial wall. We have previously found that macrophages in atherosclerotic lesions secrete lysosomal hydrolases that can modify low-density-lipoprotein (LDL) in vitro to generate “hydrolase-modified LDL” (H-LDL). Here, we studied whether H-LDL exerts inflammatory effects on cultured human macrophages.

Methods and Results—Using cytokine cDNA arrays, we found that H-LDL induced expression of IL-8, but not of the anti-inflammatory cytokines IL-10 and transforming growth factor (TGF)-β, in human monocyte-derived macrophages. H-LDL induced rapid phosphorylation of the p38 mitogen-activated protein kinase (MAPK), nuclear translocation of 2 transcription factors, nuclear factor κB (NF-κB) and activator protein 1 (AP-1), and time-dependent secretion of IL-8 from the macrophages. Inhibition of MAPKs and of transcription factors showed that p38 MAPK and NF-κB, but not ERK1/2, JNK, or AP-1, were crucial for the H-LDL–induced IL-8 secretion from the macrophages.

Conclusions—The results show that by activating p38 MAPK and NF-κB, macrophage hydrolases modify LDL into biologically active particles capable of triggering the secretion of IL-8 in macrophages. Thus, activated hydrolase-secreting macrophages in atherosclerotic lesions may sustain a proatherogenic extracellular environment by hydrolyzing LDL and triggering it to act in an autocrine or paracrine fashion to induce IL-8 secretion by the plaque macrophages.
Abdominal Aortic Aneurysm
Authors: Golledge Jonathan , Muller Juanita , Daugherty Alan , Norman Paul
Published: September 2006

Abdominal aortic aneurysm (AAA) affects approximately 5% of elderly men and is responsible for a significant number of deaths in Western Countries. At present surgery by open or endovascular means is the only widely used therapy for this condition. In this review we examine the risk factors, serum, and genetic associations of AAA. Epidemiology studies suggest that smoking cessation and control of cholesterol and blood pressure should reduce the number of patients developing AAA. Natural history studies suggest that smoking cessation should reduce the rate of progression of AAA. Clear level 1 evidence for drug treatments of AAA are presently lacking; however, animal and human in vitro studies suggest that medication targeted at reducing inflammation and proteolysis are most likely to be beneficial, with limited data to support the use of statins, Angiotensin II inhibitors, and macrolides. Work has commenced in understanding which patients, identified by clinical, serum, and genotype, are more at risk of AAA progression and thus should be selected out for aggressive treatment. Well designed large multicenter randomized controlled trials are required to examine the medical treatment of AAA.
Iron Chelation Inhibits NF-κB–Mediated Adhesion Molecule Expression by Inhibiting p22
phox
Protein Expression and NADPH Oxidase Activity
Authors: Li Lixin , Frei Balz
Published: September 2006

Objective—

Excess iron may increase oxidative stress and play a role in vascular inflammation and atherosclerosis. Here we determined whether the iron chelator, desferrioxamine (DFO), ameliorates oxidative stress and cellular adhesion molecule expression in a murine model of local inflammation.

Methods and Results—

Dorsal air pouches were created in C57BL/6J mice by subcutaneous injection of air. DFO (100 mg/kg body weight) was injected into the air pouch once a day for two days followed immediately on the second day by lipopolysaccharide (LPS; 2.5 mg/kg body weight). The animals were euthanized 24 hours later for analysis of oxidative stress markers and adhesion molecules in air pouch tissue. LPS treatment enhanced protein levels of p22
phox
, a catalytic subunit of NADPH oxidase, and increased NADPH oxidase activity and levels of superoxide radicals and hydrogen peroxide. Furthermore, LPS activated NF-κB and increased expression of adhesion molecules. All of these inflammatory responses were strongly suppressed by DFO, but not iron-loaded DFO.

Conclusions—

Our data show that DFO inhibits LPS-induced, NADPH oxidase–mediated oxidative stress and, hence, NF-κB activation and adhesion molecule expression in a murine model of local inflammation. Iron chelation may be helpful in treating atherosclerotic vascular diseases by ameliorating oxidative stress and inflammation.