bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous Posterior Fossa Extradural Hematoma – A Rare Complication following Cardiac Surgery
Authors: Ahmad Faiz Uddin , Pandey Paritosh , Mahapatra Ashok Kumar
Published: May 2005

Posterior fossa extradural hematoma (PFEDH) is an infrequent condition. Though numerous neuropathological sequelae of cardiopulmonary bypass have been described, to the best of the authors’ knowledge, PFEDH after cardiac surgery has not been reported in the English literature. We report a 4-year-old boy with tricuspid atresia, who underwent cardiac surgery under cardiopulmonary bypass. On the 2nd postoperative day, his neurological condition deteriorated, and a CT scan of the head revealed a large PFEDH with mass effect and hydrocephalus. He underwent a midline suboccipital craniectomy and evacuation of PFEDH. There was diffuse bleeding from the dura; however, no specific site of bleeding was identified. The child started following commands on the 1st postoperative day, had an uneventful recovery and was discharged on the 10th postoperative day. On follow-up, 1 year after the surgery, he was doing well.
Developmental Dyslexia – Recurrence Risk Estimates from a German Bi-Center Study Using the Single Proband Sib Pair Design
Authors: Ziegler Andreas , König Inke R. , Deimel Wolfgang , Plume Ellen , Nöthen Markus M. , Propping Peter , Kleensang André , Müller-Myhsok Bertram , Warnke Andreas , Remschmidt Helmut , Schulte-Körne Gerd
Published: May 2005

Objective: Several studies have demonstrated a genetic component for dyslexia. However, both segregation and linkage analyses show contradictory results pointing at the necessity of an optimal ascertainment scheme for molecular genetic studies. Previously, we have argued that the single proband sib pair design (SPSP) would be optimal. The aims of this paper therefore are to demonstrate the practicability of the SPSP design and the estimation of recurrence risks for reading and writing. Methods: We assessed spelling and reading in a family sample ascertained through the SPSP design. 287 families with at least two siblings and their parents were recruited. At least one child was affected with spelling disorder according to a one standard deviation (1SD) discrepancy criterion. Results: Mean values for probands and their siblings were different for both the spelling and the reading phenotype. For the probands, variances of the phenotype spelling were smaller. These effects became stronger with more extreme selection criteria. Both siblings fulfilled the 1SD criterion for spelling and reading in 60.3 and 28.9% of the families, respectively, indicating a low cost efficiency of the double proband sib pair approach. A recurrence risk of 4.52 (CI: 4.07–4.93) was obtained for spelling when the 1SD criterion was applied to both siblings. Recurrence risk estimates were similar for reading. Conclusion: The study demonstrates the suitability of the SPSP design for genetic analysis of dyslexia. The recurrence risk estimates may be used for determining sample sizes in gene mapping studies.
Mutant Prevention Concentration of Isoniazid, Rifampicin and Rifabutin against Mycobacterium tuberculosis
Authors: Rodríguez J.C. , Cebrián L. , Ruiz M. , López M. , Royo G.
Published: May 2005

Background: Mutant prevention concentration (MPC) is a new parameter that may be of aid in determining the risk of resistant mutants being selected. Methods: The MPCs of 224 Mycobacterium tuberculosis clinical isolates were estimated by plating more than 1010 cells on drug-containing agar and determining the concentration that allowed no colony growth. Antibiotics used were isoniazid, rifampicin and rifabutin. Results: The MPC90 of clinical isolates in our setting is 2.4, 2.2 and 0.4 mg/l for isoniazid, rifampicin and rifabutin, respectively. Conclusions: Isoniazid and rifampicin are two drugs that present a low risk of selection of resistant mutants when used in monotherapy. However, determination of the MPC of each strain can provide data to minimize this risk and thus enable treatment to be optimized.
Fourth-Generation Cephalosporins: In vitro Activity against Nosocomial Gram-Negative Bacilli Compared with β-Lactam Antibiotics and Ciprofloxacin
Authors: Tumah Haitham
Published: May 2005

The in vitro activity of two new expanded spectrum fourth-generation cephalosporins, cefepime and cefpirome, was compared with that of five antibacterial agents, ceftazidime, cefoperazone, cefotaxime, imipenem, and ciprofloxacin, that are commonly used in the treatment of serious infections caused by aerobic gram-negative bacteria. The agar dilution method described by the US National Committee for Clinical Laboratory Standards was used to determine the minimum inhibitory concentrations of antibiotics tested. Three hundred and two clinical isolates, representing a cross-section of Klebsiella and Enterobacter species and Pseudomonas aeruginosa were tested. The most potent β-lactams were imipenem, cefepime, and cefpirome, which demonstrated significant activity against the majority of strains in all three genera of bacteria, as did ciprofloxacin. Ceftazidime was active against P. aeruginosa, but was less potent against Klebsiella and Enterobacter species. Cefoperazone and cefotaxime were less active than ceftazidime against P. aeruginosa. Cefepime had slightly greater activity than cefpirome against the gram-negative bacteria tested. These data indicate that cefepime and cefpirome are highly active against many frequently resistant nosocomial bacterial strains that are traditionally responsible for difficult-to-treat infections.
No pre-existing bias in sailfin molly females, Poecilia latipinna, for a sword in males
Authors: Klink Karin B. , Witte Klaudia
Published: May 2005

The origination of female mate preference is still not well known and may depend on genetic predispositions, social environment and sensory stimuli in the environment. Females of different populations, which live in different environments, may therefore differ in a pre-existing bias for male traits. Previous studies within the genus Xiphophorus and Priapella (Poeciliidae) have indicated that females have a latent preference for a sword in males, even though conspecific males do not express a sword. In a recent study Basolo (2002a) found such a pre-existing bias for artificially sworded males in sailfin molly females from a Louisiana population. To investigate whether Poecilia latipinna females exhibit in general a pre-existing bias for sworded males or whether populations differ in a pre-existing female preference for sworded males, we tested P. latipinna females from a Texas population for a latent preference for sworded males. We tested in video playback experiments whether sailfin molly females P. latipinna have a latent preference for males with an artificial coloured plastic sword on TV monitors. Using video playbacks we first showed in a conditioning experiment that females perceived yellow plastic swords. Females preferred to associate with conspecific males to conspecific females on TV monitors. Females, however, did not exhibit a preference for males with a coloured sword over males with a transparent sword. Our result contradicts results of a previous study showing that sailfin molly females from a different population exhibited a preference for live males with an artificial sword. Pre-existing biases for novel male traits in females may differ between populations within a species. Thus, environmental factors may influence the development of pre-existing biases and might, therefore, drive the evolution of latent preferences in different populations differently.
Examining the Landscape of Indiana’s Nonprofit Sector
Authors: Grønbjerg Kirsten A. , Clerkin Richard M.
Published: May 2005

The authors examine technical aspects of surveying nonprofits to determine whether inferences about characteristics of the sector depend on how samples are selected. Using a stratified sample drawn from a comprehensive nonprofit database, they analyze how major profile features of the nonprofit sector vary by sampling source and by how broadly researchers define the sector. The results reveal significant differences in the accuracy, completeness, and response rates associated with alternative sampling sources. Nonprofits found on multiple listings respond at higher rates and are more formalized than those found on only one sampling source, and sampling sources vary in the profiles they generate for the nonprofit sector. The authors conclude that researchers who wish to generalize their findings to the full nonprofit sector should consider the list of incorporated nonprofits as a sampling frame—it is among the most efficient and produces the fewest distortions in nonprofit profile features.
Using Existing Teams to Teach about Teams: How an MBA Course in Managing Teams Helps Students and the Program
Authors: Isabella Lynn A.
Published: May 2005

This article chronicles the unique manner in which a second-year MBA elective course in managing teams has been crafted using existing first-year learning teams as its core. The design and orchestration of this course are detailed, as are the challenges posed, in delivering a course that not only teaches about teams and team dynamics but does so integrating first- and second-year MBA experiences. Recognizing that some features are specific to the MBA context in which this course was designed, this article also offers the underlying generalizable and adaptable features for other teams’ courses.
Teaching an Issues-Based Interdisciplinary Course: Diversity in Management and Marketing
Authors: Hazen Mary Ann , Higby Mary A.
Published: May 2005

The authors examine their experiences of coteaching an intensive, interdisciplinary elective course for MBA students: Diversity in Management and Marketing. They address otherness, dialogue, energy, and change within this course and clarify issues that can arise when coteaching interdisciplinary courses. The authors list implications for instructors of all business-related courses.
Three on Three: A Tale for Business Ethics Classes
Authors: VanSandt Craig V.
Published: May 2005

This article presents a novel approach to teaching business ethics to college students by relying on well-known aids to learning new, complex, and/or abstract material. The primary purpose of this article is threefold: (a) to explore some of the reasons why learning the basics of moral philosophies is relatively difficult for many students; (b) to review some of the proven methods of helping students learn complex and abstract concepts; and (c) to introduce a specific method that the author has used to help students more effectively learn about the most widely used moral philosophies.
On the Relationship between Authority Size and the Costs of Providing Local Services: Lessons for the Design of Intergovernmental Transfers in Spain
Authors: Solé-Ollé Albert , Bosch Núria
Published: May 2005

Unconditional transfers to local governments in Spain are distributed mainly according to weighted population, with weights rising with population size to account for the higher expenditure responsibilities and needs of bigger municipalities. The authors evaluate the appropriateness of these weights and estimate an expenditure equation with a data set covering more than 2,500 Spanish municipalities in 1999, and the use of a piecewise linear function accounts for the possible nonlinear relationship between costs and population size. The results identify important scale economies for the smallest local authorities and growing per capita costs for higher population sizes. However, the growth in per capita costs is much lower than the one implicit in the weights used in the distribution of transfers.
Drug therapy for acute myeloid leukemia
Authors: Tallman Martin S. , Gilliland D. Gary , Rowe Jacob M.
Published: May 2005

Although improvement in outcomes has occurred in younger adults with acute myeloid leukemia (AML) during the past 4 decades, progress in older adults has been much less conspicuous, if at all. Approximately 50% to 75% of adults with AML achieve complete remission (CR) with cytarabine and an anthracycline such as daunorubicin or idarubicin or the anthracenedione mitoxantrone. However, only approximately 20% to 30% of the patients enjoy long-term disease survival. Various postremission strategies have been explored to eliminate minimal residual disease. The optimal dose, schedule, and number of cycles of postremission chemotherapy for most patients are not known. A variety of prognostic factors can predict outcome and include the karyotype of the leukemic cells and the presence of transmembrane transporter proteins, which extrude certain chemotherapy agents from the cell and confer multidrug resistance and mutations in or over expressions of specific genes such as WT1, CEBPA, BAX and the ratio of BCL2 to BAX, BAALC, EVI1, KIT, and FLT3. Most recently, insights into the molecular pathogenesis of AML have led to the development of more specific targeted agents and have ushered in an exciting new era of antileukemia therapy. Such agents include the immunoconjugate gemtuzumab ozogamicin, multidrug resistance inhibitors, farnesyl transferase inhibitors, histone deacetylase and proteosome inhibitors, antiangiogenesis agents, Fms-like tyrosine kinase 3 (FLT3) inhibitors, and apoptosis inhibitors.
A novel stem-cell population in adult liver with potent hematopoietic-reconstitution activity
Authors: Kotton Darrell N. , Fabian Attila J. , Mulligan Richard C.
Published: May 2005

A number of recent reports have documented that cells possessing hematopoietic-reconstitution ability can be identified and isolated from a variety of solid organs in the adult animal. In all studies to date, however, purified organ-derived stem cells demonstrate a diminished repopulating capacity relative to that of purified bone marrow–derived hematopoietic stem cells (BM HSCs). It has therefore been unclear whether organ-derived HSCs possess functional properties distinct from those of BM HSCs, or simply have not been purified to a comparable extent. Here we report the identification of a rare subset of cells in adult murine liver that possess potent blood-repopulating potential, approaching that of BM HSCs. The cells, isolated on the basis of dye-efflux activity and CD45 expression (termed CD45+ liver side population [SP] tip cells), exhibit a surface phenotype similar to that of freshly isolated BM HSCs derived from normal adult animals, but are phenotypically distinct in that they do not express the stem-cell marker c-kit. Single-cell transplantation studies indicate that CD45+ liver SP tip cells can be generated from BM HSCs, suggesting a relationship between stem-cell populations in the liver and bone marrow compartments. Overall, these studies have important implications for understanding extramedullary hematopoiesis, and may be relevant to current strategies aimed at inducing tolerance to transplanted organs.
Refined repetitive sequence searches utilizing a fast hash function and cross species information retrievals
Authors: Reneker Jeff , Shyu Chi-Ren
Published: May 2005

Background

Searching for small tandem/disperse repetitive DNA sequences streamlines many biomedical research processes. For instance, whole genomic array analysis in yeast has revealed 22 PHO-regulated genes. The promoter regions of all but one of them contain at least one of the two core Pho4p binding sites, CACGTG and CACGTT. In humans, microsatellites play a role in a number of rare neurodegenerative diseases such as spinocerebellar ataxia type 1 (SCA1). SCA1 is a hereditary neurodegenerative disease caused by an expanded CAG repeat in the coding sequence of the gene. In bacterial pathogens, microsatellites are proposed to regulate expression of some virulence factors. For example, bacteria commonly generate intra-strain diversity through phase variation which is strongly associated with virulence determinants. A recent analysis of the complete sequences of the Helicobacter pylori strains 26695 and J99 has identified 46 putative phase-variable genes among the two genomes through their association with homopolymeric tracts and dinucleotide repeats. Life scientists are increasingly interested in studying the function of small sequences of DNA. However, current search algorithms often generate thousands of matches – most of which are irrelevant to the researcher.

Results

We present our hash function as well as our search algorithm to locate small sequences of DNA within multiple genomes. Our system applies information retrieval algorithms to discover knowledge of cross-species conservation of repeat sequences. We discuss our incorporation of the Gene Ontology (GO) database into these algorithms. We conduct an exhaustive time analysis of our system for various repetitive sequence lengths. For instance, a search for eight bases of sequence within 3.224 GBases on 49 different chromosomes takes 1.147 seconds on average. To illustrate the relevance of the search results, we conduct a search with and without added annotation terms for the yeast Pho4p binding sites, CACGTG and CACGTT. Also, a cross-species search is presented to illustrate how potential hidden correlations in genomic data can be quickly discerned. The findings in one species are used as a catalyst to discover something new in another species. These experiments also demonstrate that our system performs well while searching multiple genomes – without the main memory constraints present in other systems.

Conclusion

We present a time-efficient algorithm to locate small segments of DNA and concurrently to search the annotation data accompanying the sequence. Genome-wide searches for short sequences often return hundreds of hits. Our experiments show that subsequently searching the annotation data can refine and focus the results for the user. Our algorithms are also space-efficient in terms of main memory requirements. Source code is available upon request.
Parallel organization of contralateral and ipsilateral prefrontal cortical projections in the rhesus monkey
Authors: Barbas Helen , Hilgetag Claus C , Saha Subhash , Dermon Caterina R , Suski Joanna L
Published: May 2005

Background

The neocortical commissures have a fundamental role in functional integration across the cerebral hemispheres. We investigated whether commissural projections in prefrontal cortices are organized according to the same or different rules as those within the same hemisphere, by quantitatively comparing density, topography, and laminar origin of contralateral and ipsilateral projections, labeled after unilateral injection of retrograde tracers in prefrontal areas.

Results

Commissural projection neurons constituted less than one third of the ipsilateral. Nevertheless, projections from the two hemispheres were strongly correlated in topography and relative density. We investigated to what extent the distribution of contralateral projections depended on: (a) geographic proximity of projection areas to the area homotopic to the injection site; (b) the structural type of the linked areas, based on the number and neuronal density of their layers. Although both measures were good predictors, structural type was a comparatively stronger determinant of the relative distribution and density of projections. Ipsilateral projection neurons were distributed in the superficial (II-III) and deep (V-VI) layers, in proportions that varied across areas. In contrast, contralateral projection neurons were found mostly in the superficial layers, but still showed a gradient in their distribution within cortical layers that correlated significantly with cortical type, but not with geographic proximity to the homotopic area.

Conclusion

The organization of ipsilateral and contralateral prefrontal projections is similar in topography and relative density, differing only by higher overall density and more widespread laminar origin of ipsilateral than contralateral projections. The projections on both sides are highly correlated with the structural architecture of the linked areas, and their remarkable organization is likely established by punctuated development of distinct cortical types. The preponderance of contralateral projections from layer III may be traced to the late development of the callosal system, whose function may be compromised in diseases that have their root late in ontogeny.
Effects of redox cycling compounds on DT diaphorase activity in the liver of rainbow trout (Oncorhynchus mykiss)
Authors: Sturve Joachim , Stephensen Eiríkur , Förlin Lars
Published: May 2005

Background

DT diaphorase (DTD; NAD(P)H:quinone oxidoreductase; EC 1.6.99.2) catalyses the two electron reduction of quinones, thus preventing redox cycling and consequently quinone dependent production of reactive oxygen species. In rat and mouse, a wide range of chemicals including polyaromatic hydrocarbons, azo dyes and quinones induces DTD. Bifunctional compounds, such as β-naphthoflavone (β-NF) and benzo(a)pyrene (B(a)P), induce DTD together with CYP1A and phase II enzymes by a mechanism involving the aryl hydrocarbon receptor (AHR). Monofunctional induction of DTD is mediated through the antioxidant response element and does not lead to the induction of AHR dependent enzymes, such as CYP1A. The aim of this study was to investigate the effects of prooxidants (both bifunctional and monofunctional) on the activity of hepatic DTD in rainbow trout (Oncorhynchus mykiss) in order to evaluate DTD suitability as a biomarker. We also investigated the effect of β-NF on hepatic DTD activity in perch (Perca fluviatilis), shorthorn sculpin (Myoxocephalus scorpius), eelpout (Zoarces viviparus), brown trout (Salmo trutta) and carp (Cyprinus carpio). In addition, the effect of short term exposure to prooxidants on catalase activity was investigated.

Results

In rainbow trout, hepatic DTD activity is induced by the bifunctional AHR agonists β-NF and B(a)P and the monofunctional inducers naphthazarin, menadione and paraquat. Although exposure to both B(a)P and β-NF led to a strong 7-ethoxyresorufin-O-deethylase (EROD) induction, none of the monofunctional compounds affected the rainbow trout EROD activity. DTD was not induced by β-NF in any of the other fish species. Much higher DTD activities were observed in rainbow trout compared to the other fish species. Catalase activity was less responsive to short term exposure to prooxidants compared to DTD.

Conclusion

Since rainbow trout hepatic DTD activity is inducible by both monofunctional and bifunctional inducers, it is suggested that rainbow trout DTD may be regulated by the same mechanisms, as in mammals. The fact that DTD is inducible in rainbow trout suggests that the enzyme may be suitable as a part of a biomarker battery when rainbow trout is used in environmental studies. It appears as if DTD activity in rainbow trout is higher and inducible compared to the other fish species studied.
Coping, quality of life, and hope in adults with primary antibody deficiencies
Authors: Sigstad Hanne Marie Høybråten , Stray-Pedersen Asbjørg , Frøland Stig S
Published: May 2005

Background

Living with a chronic disease, such as primary antibody deficiency, will often have consequences for quality of life. Previous quality-of-life studies in primary antibody deficiency patients have been limited to different treatment methods. We wanted to study how adults with primary antibody deficiencies manage their conditions and to identify factors that are conducive to coping, good quality of life and hope.

Methods

Questionnaires were sent to all patients ≥20 years of age with primary antibody deficiencies who were served by Rikshospitalet University Hospital. The questionnaires consisted of several standardized scales: Ferrans and Powers Quality of Life Index (QLI), Short Form-36 (SF-36), Jalowiec Coping Scale (JCS), Nowotny Hope Scale (NHS), and one scale we devised with questions about resources and pressures in the past. Of a total of 91, 55 patients (aged 23–76 years) answered the questionnaires. The questionnaire study were supplemented with selected interviews of ten extreme cases, five with low and five with high quality of life scores.

Results

Among the 55 patients, low quality of life scores were related to unemployment, infections in more than four organs, more than two additional diseases, or more than two specific occurrences of stress in the last 2–3 months. Persons with selective IgA deficiency had significantly higher QLI scores than those with other antibody deficiencies. An optimistic coping style was most frequent used, and hope values were moderately high. Based on the interviews, the patients could be divided into three groups: 1) low QLI scores, low hope values, and reduced coping, 2) low QLI scores, moderate hope values, and good coping, and 3) high QLI scores, moderate to strong hope values, and good coping. Coping was related to the patients' sense of closeness and competence.

Conclusion

Low quality of life scores in adults with primary antibody deficiencies were linked to unemployment and disease-related strains. Closeness and competence were preconditions for coping, quality of life and hope. The results are valuable in planning care for this patient group.
Pediatric appendicitis rupture rate: a national indicator of disparities in healthcare access
Authors: Jablonski Kathleen A , Guagliardo Mark F
Published: May 2005

Background

The U.S. National Healthcare Disparities Report is a recent effort to measure and monitor racial and ethnic disparities in health and healthcare. The Report is a work in progress and includes few indicators specific to children. An indicator worthy of consideration is racial/ethnic differences in the rate of bad outcomes for pediatric acute appendicitis. Bad outcomes for this condition are indicative of poor access to healthcare, which is amenable to social and healthcare policy changes.

Methods

We analyzed the KID Inpatient Database, a nationally representative sample of pediatric hospitalization, to compare rates of appendicitis rupture between white, African American, Hispanic and Asian children. We ran weighted logistic regression models to obtain national estimates of relative odds of rupture rate for the four groups, adjusted for developmental, biological, socioeconomic, health services and hospital factors that might influence disease outcome.

Results

Rupture was a much more burdensome outcome than timely surgery and rupture avoidance. Rupture cases had 97% higher hospital charges and 175% longer hospital stays than non-rupture cases on average. These burdens disproportionately affected minority children, who had 24% – 38% higher odds of appendicitis rupture than white children, adjusting for age and gender. These differences were reduced, but remained significant after adjusting for other factors.

Conclusion

The racial/ethnic disparities in pediatric appendicitis outcome are large and are preventable with timely diagnosis and surgery for all children. Furthermore, estimating this disparity using the KID survey is a relatively straightforward process. Therefore pediatric appendicitis rupture rate is a good candidate for inclusion in the National Healthcare Disparities Report. As with most other health and healthcare disparities, efforts to reduce disparities in income, wealth and access to care will most likely improve the odds of favorable outcome for this condition as well.
The Open Microscopy Environment (OME) Data Model and XML file: open tools for informatics and quantitative analysis in biological imaging
Authors: Goldberg Ilya G , Allan Chris , Burel Jean-Marie , Creager Doug , Falconi Andrea , Hochheiser Harry , Johnston Josiah , Mellen Jeff , Sorger Peter K , Swedlow Jason R
Published: May 2005

The Open Microscopy Environment (OME) defines a data model and a software implementation to serve as an informatics framework for imaging in biological microscopy experiments, including representation of acquisition parameters, annotations and image analysis results. OME is designed to support high-content cell-based screening as well as traditional image analysis applications. The OME Data Model, expressed in Extensible Markup Language (XML) and realized in a traditional database, is both extensible and self-describing, allowing it to meet emerging imaging and analysis needs.
Association of hnRNP S1 proteins with vimentin intermediate filaments in migrating cells
Authors: Inoue Akira , Watanabe Takanori , Tominaga Kazunari , Tsugawa Katsuji , Nishio Koji , Takahashi Kenichi P. , Kaneda Kenji
Published: May 2005

S1 proteins C2 and D2 are multifunctional hnRNP proteins acting as transcriptional regulators in the nucleus. Immunofluorescence staining of various cells in culture revealed that S1 proteins also occur in the cytoplasm, often in association with vimentin intermediate filaments (VFs). Here, we verified the association of S1 proteins with vimentin using vimentin-deficient cells, crosslinking and immunoprecipitation, and further investigated the biological significance of this association. S1 proteins on VFs, referred to here as S1 fibers, were lost in highly confluent cells, where cell proliferation and cellular metabolic activity greatly decreased owing to cell density-dependent arrest. However, the disappearance of S1 fibers was not related to these reduced activities, but to inhibited cell migration. Although undetected in cells of non-migratory tissues as well as in confluent cultured cells, S1 fibers were found in all migratory cells examined, such as cultured cells in scratch/wound experiments, blood neutrophils and monocytes, and fibroblasts engaging in tissue healing. In addition, S1 fibers reappeared even in confluent cells when VFs were induced to reorganize with okadaic acid. We propose that S1 proteins occur in association with VFs in migratory cells. Possible participation of S1 proteins in the formation/reorganization of VFs is discussed.
tGolgin-1 (p230, golgin-245) modulates Shiga-toxin transport to the Golgi and Golgi motility towards the microtubule-organizing centre
Authors: Yoshino Atsuko , Setty Subba Rao Gangi , Poynton Clare , Whiteman Eileen L. , Saint-Pol Agnès , Burd Christopher G. , Johannes Ludger , Holzbaur Erika L. , Koval Michael , McCaffery J. Michael , Marks Michael S.
Published: May 2005

tGolgin-1 (trans-Golgi p230, golgin-245) is a member of a family of large peripheral membrane proteins that associate with the trans-Golgi network (TGN) via a C-terminal GRIP domain. Some GRIP-domain proteins have been implicated in endosome-to-TGN transport but no function for tGolgin-1 has been described. Here, we show that tGolgin-1 production is required for efficient retrograde distribution of Shiga toxin from endosomes to the Golgi. Surprisingly, we also found an indirect requirement for tGolgin-1 in Golgi positioning. In HeLa cells depleted of tGolgin-1, the normally centralized Golgi and TGN membranes were displaced to the periphery, forming `mini stacks'. These stacks resembled those in cells with disrupted microtubules or dynein-dynactin motor, in that they localized to endoplasmic-reticulum exit sites, maintained their secretory capacity and cis-trans polarity, and were relatively immobile by video microscopy. The mini stacks formed concomitant with a failure of pre-Golgi elements to migrate along microtubules towards the microtubule-organizing centre. The requirement for tGolgin-1 in Golgi positioning did not appear to reflect direct binding of tGolgin-1 to motile pre-Golgi membranes, because distinct Golgi and tGolgin-1-containing TGN elements that formed after recovery of HeLa cells from brefeldin-A treatment moved independently toward the microtubule-organizing centre. These data demonstrate that tGolgin-1 functions in Golgi positioning indirectly, probably by regulating retrograde movement of cargo required for recruitment or activation of dynein-dynactin complexes on newly formed Golgi elements.
MMP-1 activation by serine proteases and MMP-10 induces human capillary tubular network collapse and regression in 3D collagen matrices
Authors: Saunders W. Brian , Bayless Kayla J. , Davis George E.
Published: May 2005

Previous work has shown that endothelial cell (EC)-derived matrix metalloproteinases (MMPs) regulate regression of capillary tubes in vitro in a plasmin- and MMP-1 dependent manner. Here we report that a number of serine proteases can activate MMP-1 and cause capillary tube regression; namely plasma kallikrein, trypsin, neutrophil elastase, cathepsin G, tryptase and chymase. Plasma prekallikrein failed to induce regression without coactivators such as high molecular weight kininogen (HMWK) or coagulation Factor XII. The addition of trypsin, the neutrophil serine proteases (neutrophil elastase and cathepsin G) and the mast cell serine proteases (tryptase and chymase) each caused MMP-1 activation and collagen type I proteolysis, capillary tubular network collapse, regression and EC apoptosis. Capillary tube collapse is accompanied by collagen gel contraction, which is strongly related to the wound contraction that occurs during regression of granulation tissue in vivo. We also report that proMMP-10 protein expression is markedly induced in ECs undergoing capillary tube morphogenesis. Addition of each of the serine proteases described above led to activation of proMMP-10, which also correlated with MMP-1 activation and capillary tube regression. Treatment of ECs with MMP-1 or MMP-10 siRNA markedly delayed capillary tube regression, whereas gelatinase A (MMP-2), gelatinase B (MMP-9) and stromelysin-1 (MMP-3) siRNA-treated cells behaved in a similar manner to controls and regressed normally. Increased expression of MMP-1 or MMP-10 in ECs using recombinant adenoviral delivery markedly accelerated serine protease-induced capillary tube regression. ECs expressing increased levels of MMP-10 activated MMP-1 to a greater degree than control ECs. Thus, MMP-10–induced activation of MMP-1 correlated with tube regression and gel contraction. In summary, our work demonstrates that MMP-1 zymogen activation is mediated by multiple serine proteases and MMP-10, and that these events are central to EC-mediated collagen degradation and capillary tube regression in 3D collagen matrices.
SYCP2 and SYCP3 are required for cohesin core integrity at diplotene but not for centromere cohesion at the first meiotic division
Authors: Kouznetsova Anna , Novak Ivana , Jessberger Rolf , Höög Christer
Published: May 2005

Much of the organization of the meiotic prophase-I chromosome axis is attributed to two groups of proteins: the axial element proteins, SYCP2 and SYCP3; and the cohesin-complex proteins. Although the cohesin-complex proteins ensure that sister chromatids remain paired during meiosis, the role of SYCP2 and SYCP3 is not clear. Interestingly, it has been shown that SYCP3 and SYCP2 associate with the centromere regions of male, but not female, metaphase-I chromosomes, suggesting a sex-specific function for the two proteins. We have analysed the spatial distribution of cohesin-complex proteins associated with meiotic chromosomes in germ cells derived from Sycp3-deficient female and male mice. We show that, in the absence of SYCP3, the cohesin cores associated with the female meiotic chromosomes disassemble prematurely at the diplotene stage of meiosis. We also show that SYCP3 and SYCP2 are not required for centromere cohesion at the metaphase-I stage in male germ cells. We conclude that SYCP3 has a temporally restricted role in maintaining, but not establishing, cohesin-core organization during prophase I. This finding supports a model in which the removal of bulk cohesin from paired sister chromatids at late prophase in both meiotic and mitotic cells ensures proper chromosome compaction and segregation.
Tramadol Exposures Reported to Statewide Poison Control System
Authors: Marquardt Kathy A , Alsop Judith A , Albertson Timothy E
Published: May 2005

BACKGROUND:

Tramadol is a unique analgesic that has been associated with seizures on overdose.

OBJECTIVE:

To determine the toxic effects associated with tramadol exposure.

METHODS:

A retrospective chart review of tramadol exposures reported to a multisite, state-wide poison control system over a 2.5-year period was performed.

RESULTS:

A total of 602 cases were retrieved; 190 had sufficient data for study evaluation. Cases with coingestants or unknown outcomes were eliminated. Of the 190 remaining cases, 55% were females. Acute ingestions represented 90.0%, chronic ingestions 7.9%, and acute on chronic 2.1% of the overdoses. Ages of the patients ranged from 9 months to 80 years. Suicide attempts represented the largest group of exposures. Main symptoms included central nervous system (CNS) depression (27.4%), nausea and vomiting (21.1%), tachycardia (17.4%), and seizures (13.7%). Dosage ranged from a taste amount to 5000 mg. The smallest amount of tramadol associated with seizure was 200 mg, and 84.6% of seizures occurred within 6 hours of time of ingestion. Logistic regression analysis showed an association between seizures and tramadol use in males, chronic use, suicide attempts, intentional abuse or misuse, and tachycardia (HR >100 beats/min). No effect was seen in 36.3% of patients, minor effects in 43.7%, moderate effects in 19.5%, and major effects in 0.5%. Symptoms resolved within 24 hours in 96.7% of the 121 patients who had symptoms. Naloxone improved CNS depression in 7 of 8 patients in whom a response was documented.

CONCLUSIONS:

Tramadol overdoses frequently cause CNS depression, nausea/vomiting, tachycardia, and seizures. Symptoms generally resolve within 24 hours. Accidental ingestions in children were well tolerated, primarily causing sedation.
SPARC-thrombospondin-2-double-null Mice Exhibit Enhanced Cutaneous Wound Healing and Increased Fibrovascular Invasion of Subcutaneous Polyvinyl Alcohol Sponges
Authors: Puolakkainen Pauli A. , Bradshaw Amy D. , Brekken Rolf A. , Reed May J. , Kyriakides Themis , Funk Sarah E. , Gooden Michel D. , Vernon Robert B. , Wight Thomas N. , Bornstein Paul , Sage E. Helene
Published: May 2005

Secreted protein acidic and rich in cysteine (SPARC) and thrombospondin-2 (TSP-2) are structurally unrelated matricellular proteins that have important roles in cell- extracellular matrix (ECM) interactions and tissue repair. SPARC-null mice exhibit accelerated wound closure, and TSP-2-null mice show an overall enhancement in wound healing. To assess potential compensation of one protein for the other, we examined cutaneous wound healing and fibrovascular invasion of subcutaneous sponges in SPARC-TSP-2 (ST) double-null and wild-type (WT) mice. Epidermal closure of cutaneous wounds was found to occur significantly faster in ST-double-null mice, compared with WT animals: histological analysis of dermal wound repair revealed significantly more mature phases of healing at 1, 4, 7, 10, and 14 days after wounding, and electron microscopy showed disrupted ECM at 14 days in these mice. ST-double-null dermal fibroblasts displayed accelerated migration, relative to WT fibroblasts, in a wounding assay in vitro, as well as enhanced contraction of native collagen gels. Zymography indicated that fibroblasts from ST-double-null mice also produced higher levels of matrix metalloproteinase (MMP)-2. These data are consistent with the increased fibrovascular invasion of subcutaneous sponge implants seen in the double-null mice. The generally accelerated wound healing of ST-double-null mice reflects that described for the single-null animals. Importantly, the absence of both proteins results in elevated MMP-2 levels. SPARC and TSP-2 therefore perform similar functions in the regulation of cutaneous wound healing, but fine-tuning with respect to ECM production and remodeling could account for the enhanced response seen in ST-double-null mice.
Presence of Anti-cystatin C–positive Dendritic Cells or Macrophages and Localization of Cysteine Proteases in the Apical Bud of the Enamel Organ in the Rat Incisor
Authors: Nishikawa Sumio
Published: May 2005

Cystatin C, a cysteine protease inhibitor, was examined in the apical buds of rat incisors by immunohistochemistry, because in transition and maturation zones most of the dendritic cells in the papillary layer are anti-cystatin C–positive. Anti-cystatin C–labeled cells were sparse and localized to the proliferation and differentiation zones, constituting the apical bud of 5-week-old rat incisors. These cells were considered macrophages or dendritic cells, based on their reactivity with OX6 and ED1, as well as their ultrastructure. Basement membrane at the periphery of apical bud was also labeled by anti-cystatin C antibody. The apical buds included a few apoptotic fragments and weak reactivity with antibody to cathepsin L, a cysteine protease. Reactivity to anti-cystatin C and anti-cathepsin ∗∗∗L antibodies was also detected in the apical bud of newborn rat incisors. These results suggest that the cystatin C–positive macrophages or dendritic cells are involved in normal incisor formation. They may be related to the clearance of apoptotic cells or protection from putative cysteine protease activity.
BRCA1 Gene Expression in Breast Cancer: A Correlative Study between Real-time RT-PCR and Immunohistochemistry
Authors: Al-Mulla Fahd , Abdulrahman Mahera , Varadharaj Govindarajulu , Akhter Nadeem , Anim Jehoram T.
Published: May 2005

Breast cancer is a major cause of cancer-related mortality in women. There are major discrepancies concerning the usefulness of various antibodies in detecting breast cancer susceptibility gene 1 (BRCA1) protein and its subcellular localization. The aim of the present study was to determine the specificity and sensitivity of immunohistochemistry (IHC) as a screening method for demonstrating BRCA1 expression. BRCA1 gene expression in archival paraffin-embedded breast cancer tissues was studied simultaneously at the protein and mRNA levels, and the two findings were compared. Forty-eight archival paraffin-embedded breast cancer tissues were studied for BRCA1 gene expression at protein level by IHC using four different antibodies against different BRCA1 epitopes and at mRNA level using real-time RT-PCR. BRCA1 mRNA expression was reduced or absent in 79% of the samples, and this finding correlated significantly with loss of BRCA1 protein expression in 83% of breast cancer tissues using one BRCA1 antibody studied (AB-1, against N-terminus epitope). The specificity of this antibody was 91.3%, and its sensitivity was 66.6%. There was no significant correlation between BRCA1 mRNA and protein expression as demonstrated by the remaining three antibodies. Antibody 8F7 had the highest sensitivity of 100%, but its specificity was 30.4% if mRNA levels were considered as the reference standard.
An Event-Related Functional Magnetic Resonance Imaging Study of Voluntary and Stimulus-Driven Orienting of Attention
Authors: Kincade J. Michelle , Abrams Richard A. , Astafiev Serguei V. , Shulman Gordon L. , Corbetta Maurizio
Published: May 2005

Attention can be voluntarily directed to a location or automatically summoned to a location by a salient stimulus. We compared the effects of voluntary and stimulus-driven shifts of spatial attention on the blood oxygenation level-dependent signal in humans, using a method that separated preparatory activity related to the initial shift of attention from the subsequent activity caused by target presentation. Voluntary shifts produced greater preparatory activity than stimulus-driven shifts in the frontal eye field (FEF) and intraparietal sulcus, core regions of the dorsal frontoparietal attention network, demonstrating their special role in the voluntary control of attention. Stimulus-driven attentional shifts to salient color singletons recruited occipitotemporal regions, sensitive to color information and part of the dorsal network, including the FEF, suggesting a partly overlapping circuit for endogenous and exogenous orienting.

The right temporoparietal junction (TPJ), a core region of the ventral frontoparietal attention network, was strongly modulated by stimulus-driven attentional shifts to behaviorally relevant stimuli, such as targets at unattended locations. However, the TPJ did not respond to salient, task-irrelevant color singletons, indicating that behavioral relevance is critical for TPJ modulation during stimulus-driven orienting. Finally, both ventral and dorsal regions were modulated during reorienting but significantly only by reorienting after voluntary shifts, suggesting the importance of a mismatch between expectation and sensory input.
Calcineurin Triggers Reactive/Inflammatory Processes in Astrocytes and Is Upregulated in Aging and Alzheimer's Models
Authors: Norris Christopher M. , Kadish Inga , Blalock Eric M. , Chen Kuey-Chu , Thibault Veronique , Porter Nada M. , Landfield Philip W. , Kraner Susan D.
Published: May 2005

Astrocyte reactivity (i.e., activation) and associated neuroinflammation are increasingly thought to contribute to neurodegenerative disease. However, the mechanisms that trigger astrocyte activation are poorly understood. Here, we studied the Ca2+-dependent phosphatase calcineurin, which regulates inflammatory signaling pathways in immune cells, for a role in astrogliosis and brain neuroinflammation. Adenoviral transfer of activated calcineurin to primary rat hippocampal cultures resulted in pronounced thickening of astrocyte somata and processes compared with uninfected or virus control cultures, closely mimicking the activated hypertrophic phenotype. This effect was blocked by the calcineurin inhibitor cyclosporin A. Parallel microarray studies, validated by extensive statistical analyses, showed that calcineurin overexpression also induced genes and cellular pathways representing most major markers associated with astrocyte activation and recapitulated numerous changes in gene expression found previously in the hippocampus of normally aging rats or in Alzheimer's disease (AD). No genomic or morphologic evidence of apoptosis or damage to neurons was seen, indicating that the calcineurin effect was mediated by direct actions on astrocytes. Moreover, immunocytochemical studies of the hippocampus/neocortex in normal aging and AD model mice revealed intense calcineurin immunostaining that was highly selective for activated astrocytes. Together, these studies show that calcineurin overexpression is sufficient to trigger essentially the full genomic and phenotypic profiles associated with astrocyte activation and that hypertrophic astrocytes in aging and AD models exhibit dramatic upregulation of calcineurin. Thus, the data identify calcineurin upregulation in astrocytes as a novel candidate for an intracellular trigger of astrogliosis, particularly in aging and AD brain.
Control of Cellular Pattern Formation in the Vertebrate Inner Retina by Homotypic Regulation of Cell-Fate Decisions
Authors: Tyler Melinda J. , Carney Laurel H. , Cameron David A.
Published: May 2005

The vertebrate retina is composed of cellular arrays that are nonrandom across two-dimensional space. The determinants of these nonrandom two-dimensional cellular patterns in the inner nuclear layer of the retina were investigated using empirical and computational modeling techniques. In normal and experimental models of goldfish retinal growth, the patterns of tyrosine hydroxylase- and serotonin-positive cells indicated that neither cell death nor lateral migration of differentiated cells were dominant mechanisms of cellular pattern formation. A computational model of cellular pattern formation that used a signaling mechanism arising from differentiated cells that inhibited homotypic cell-fate decisions generated accurate simulations of the empirically observed patterns in normal retina. This model also predicted the principal atypical cellular pattern characteristic, a transient cell-type-specific hyperplasia, which was empirically observed in the growing retina subsequent to selective ablation of differentiated retinal cells, either tyrosine hydroxylase positive or serotonin positive. The results support the hypothesis that inhibitory spatiotemporal regulation of homotypic cell-fate decisions is a dominant mechanistic determinant of nonrandom cellular patterns in the vertebrate retina.