bluuebunny/crossref_metadata_2025 huggingface dataset:
Poisonous Programmers
Authors: Neville-Neil George
Published: March 2008

Dear KV, I hope you don’t mind if I ask you about a non-work-related problem, though I guess if you do mind you just won’t answer. I work on an open source project when I have the time, and we have some annoying nontechnical problems. The problems are really people, and I think you know the ones I mean: people who constantly fight with other members of the project over what seem to be the most trivial points, or who contribute very little to the project but seem to require a huge amount of help for their particular needs. I find myself thinking it would be nice if such people just went away, but I don’t think starting a flame war on our mailing lists over these things would really help. Any thoughts on this nontechnical problem?
Beyond Server Consolidation
Authors: Vogels Werner
Published: March 2008

Virtualization technology was developed in the late 1960s to make more efficient use of hardware. Hardware was expensive, and there was not that much available. Processing was largely outsourced to the few places that did have computers. On a single IBM System/360, one could run in parallel several environments that maintained full isolation and gave each of its customers the illusion of owning the hardware. Virtualization was time sharing implemented at a coarse-grained level, and isolation was the key achievement of the technology. It also provided the ability to manage resources efficiently, as they would be assigned to virtual machines such that deadlines could be met and a certain quality of service could be achieved.
Network Virtualization: Breaking the Performance Barrier
Authors: Rixner Scot
Published: March 2008

The recent resurgence in popularity of virtualization has led to its use in a growing number of contexts, many of which require high-performance networking. Consider server consolidation, for example. The efficiency of network virtualization directly impacts the number of network servers that can effectively be consolidated onto a single physical machine. Unfortunately, modern network virtualization techniques incur significant overhead, which limits the achievable network performance. We need new network virtualization techniques to realize the full benefits of virtualization in network-intensive domains.
Effect of acute physiological hyperinsulinemia on gene expression in human skeletal muscle in vivo
Authors: Coletta Dawn K. , Balas Bogdan , Chavez Alberto O. , Baig Muhammad , Abdul-Ghani Muhammad , Kashyap Sangeeta R. , Folli Franco , Tripathy Devjit , Mandarino Lawrence J. , Cornell John E. , DeFronzo Ralph A. , Jenkinson Christopher P.
Published: March 2008

This study was undertaken to test the hypothesis that short-term exposure (4 h) to physiological hyperinsulinemia in normal, healthy subjects without a family history of diabetes would induce a low grade inflammatory response independently of glycemic status. Twelve normal glucose tolerant subjects received a 4-h euglycemic hyperinsulinemic clamp with biopsies of the vastus lateralis muscle. Microarray analysis identified 121 probe sets that were significantly altered in response to physiological hyperinsulinemia while maintaining euglycemia. In normal, healthy human subjects insulin increased the mRNAs of a number of inflammatory genes (CCL2, CXCL2 and THBD) and transcription factors (ATF3, BHLHB2, HES1, KLF10, JUNB, FOS, and FOSB). A number of other genes were upregulated in response to insulin, including RRAD, MT, and SGK. CITED2, a known coactivator of PPARα, was significantly downregulated. SGK and CITED2 are located at chromosome 6q23, where we previously detected strong linkage to fasting plasma insulin concentrations. We independently validated the mRNA expression changes in an additional five subjects and closely paralleled the results observed in the original 12 subjects. A saline infusion in healthy, normal glucose-tolerant subjects without family history of diabetes demonstrated that the genes altered during the euglycemic hyperinsulinemic clamp were due to hyperinsulinemia and were unrelated to the biopsy procedure per se. The results of the present study demonstrate that insulin acutely regulates the levels of mRNAs involved in inflammation and transcription and identifies several candidate genes, including HES1 and BHLHB2, for further investigation.
Cross-talk between estrogen and leptin signaling in the hypothalamus
Authors: Gao Qian , Horvath Tamas L.
Published: March 2008

Obesity, characterized by enhanced food intake (hyperphagia) and reduced energy expenditure that results in the accumulation of body fat, is a major risk factor for various diseases, including diabetes, cardiovascular disease, and cancer. In the United States, more than half of adults are overweight, and this number continues to increase. The adipocyte-secreted hormone leptin and its downstream signaling mediators play crucial roles in the regulation of energy balance. Leptin decreases feeding while increasing energy expenditure and permitting energy-intensive neuroendocrine processes, such as reproduction. Thus, leptin also modulates the neuroendocrine reproductive axis. The gonadal steroid hormone estrogen plays a central role in the regulation of reproduction and also contributes to the regulation of energy balance. Estrogen deficiency promotes feeding and weight gain, and estrogen facilitates, and to some extent mimics, some actions of leptin. In this review, we examine the functions of estrogen and leptin in the brain, with a focus on mechanisms by which leptin and estrogen cooperate in the regulation of energy homeostasis.
Human heat balance during postexercise recovery: separating metabolic and nonthermal effects
Authors: Jay Ollie , Gagnon Daniel , DuCharme Michel B. , Webb Paul , Reardon Francis D. , Kenny Glen P.
Published: March 2008

Previous studies report greater postexercise heat loss responses during active recovery relative to inactive recovery despite similar core temperatures between conditions. Differences have been ascribed to nonthermal factors influencing heat loss response control since elevations in metabolism during active recovery are assumed to be insufficient to change core temperature and modify heat loss responses. However, from a heat balance perspective, different rates of total heat loss with corresponding rates of metabolism are possible at any core temperature. Seven male volunteers cycled at 75% of V̇o2peak in the Snellen whole body air calorimeter regulated at 25.0°C, 30% relative humidity (RH), for 15 min followed by 30 min of active (AR) or inactive (IR) recovery. Relative to IR, a greater rate of metabolic heat production (Ṁ − Ẇ) during AR was paralleled by a greater rate of total heat loss (ḢL) and a greater local sweat rate, despite similar esophageal temperatures between conditions. At end-recovery, rate of body heat storage, that is, [(Ṁ − Ẇ) − ḢL] approached zero similarly in both conditions, with Ṁ − Ẇ and ḢL elevated during AR by 91 ± 26 W and 93 ± 25 W, respectively. Despite a higher Ṁ − Ẇ during AR, change in body heat content from calorimetry was similar between conditions due to a slower relative decrease in ḢL during AR, suggesting an influence of nonthermal factors. In conclusion, different levels of heat loss are possible at similar core temperatures during recovery modes of different metabolic rates. Evidence for nonthermal influences upon heat loss responses must therefore be sought after accounting for differences in heat production.
Activity of Ventroposterior Thalamus Neurons During Rotation and Translation in the Horizontal Plane in the Alert Squirrel Monkey
Authors: Marlinski Vladimir , McCrea Robert A.
Published: March 2008

The firing behavior of 107 vestibular-sensitive neurons in the ventroposterior thalamus was studied in two alert squirrel monkeys during whole body rotation and translation in the horizontal plane. Vestibular-sensitive neurons were distributed primarily along the anterior and posterior borders of ventroposterior nuclei; three clusters of these neurons could be distinguished based on their location and inputs. Eighty-four neurons responded to rotation; 66 (78%) of them responded to rotation only and 18 (22%) to both rotation and translation. Forty-one neurons were sensitive to linear translation; 23 (56%) of them responded to translation only. The population rotational response to 0.5-Hz sinusoids with a peak velocity of 40°/s showed a gain of 0.23 ± 0.15 spike·s−1·deg−1·s−1 and phase lagging behind the angular velocity by −9.3 ± 34.1°. Although rotational response amplitude increased with the stimulus velocity across the range 4–100°/s, the rotational sensitivity decreased with and was inversely proportional to the stimulus velocity. The rotational response amplitude and sensitivity increased with the stimulus frequency across the range 0.2–4.0 Hz. The population response to sinusoidal translation at 0.5 Hz and 0.1 g amplitude had a gain of 111.3 ± 53.7 spikes·s−1· g−1 and lagged behind stimulus acceleration by −71.9 ± 42.6°. Translational sensitivity decreased as acceleration increased and this was inversely proportional to the square root of the acceleration. Results of this study imply that changes in the discharge rate of vestibular-sensitive thalamic neurons can be approximated using power functions of the angular and linear velocity of spatial motion.
Cardiac-directed parvalbumin transgene expression in mice shows marked heart rate dependence of delayed Ca2+buffering action
Authors: Day Sharlene M. , Coutu Pierre , Wang Wang , Herron Todd , Turner Immanuel , Shillingford Michael , LaCross Nathan C. , Converso Kimber L. , Piao Lin , Li Jingdong , Lopatin Anatoli N. , Metzger Joseph M.
Published: March 2008

Relaxation abnormalities are prevalent in heart failure and contribute to clinical outcomes. Disruption of Ca2+homeostasis in heart failure delays relaxation by prolonging the intracellular Ca2+transient. We sought to speed cardiac relaxation in vivo by cardiac-directed transgene expression of parvalbumin (Parv), a cytosolic Ca2+buffer normally expressed in fast-twitch skeletal muscle. A key feature of Parv's function resides in its Ca2+/Mg2+binding affinities that account for delayed Ca2+buffering in response to the intracellular Ca2+transient. Cardiac Parv expression decreased sarcoplasmic reticulum Ca2+content without otherwise altering intracellular Ca2+homeostasis. At high physiological mouse heart rates in vivo, Parv modestly accelerated relaxation without affecting cardiac morphology or systolic function. Ex vivo pacing of the isolated heart revealed a marked heart rate dependence of Parv's delayed Ca2+buffering effects on myocardial performance. As the pacing frequency was lowered (7 to 2.5 Hz), the relaxation rates increased in Parv hearts. However, as pacing rates approached the dynamic range in humans, Parv hearts demonstrated decreased contractility, consistent with Parv buffering systolic Ca2+. Mathematical modeling and in vitro studies provide the underlying mechanism responsible for the frequency-dependent fractional Ca2+buffering action of Parv. Future studies directed toward refining the dose and frequency-response relationships of Parv in the heart or engineering novel Parv-based Ca2+buffers with modified Mg2+and Ca2+affinities to limit systolic Ca2+buffering may hold promise for the development of new therapies to remediate relaxation abnormalities in heart failure.
Enhanced Expression of Rab27A Gene by Breast Cancer Cells Promoting Invasiveness and the Metastasis Potential by Secretion of Insulin-Like Growth Factor-II
Authors: Wang Jin-Song , Wang Fu-Bin , Zhang Qiang-Ge , Shen Zhen-Zhou , Shao Zhi-Ming
Published: March 2008

In addition to the functions of transporting melanosome in melanocytes and releasing contents of lytic granules in CTLs, Rab27A was recently shown to be involved in exocytosis of insulin and chromaffin granules in endocrine cells; it was also reported to be expressed in an exceptionally broad range of specialized secretory cells. As autocrine and paracrine cytokines are essential for invasion and metastasis in some solid tumors, blocking them may be an effective strategy to prevent tumor dissemination. In the present study, we show that Rab27A is associated with invasive and metastatic potentials of human breast cancer cells. The overexpression of Rab27A protein redistributed the cell cycle and increased the invasive and metastatic abilities in breast cancer cells both in vitro and in vivo. We also certified that Rab27A conferred the invasive and metastatic phenotypes on breast cancer cells by promoting the secretion of insulin-like growth factor-II (IGF-II), which regulates the expression of p16, vascular endothelial growth factor, matrix metalloproteinase-9, cathepsin D, cyclin D1, and urokinase-type plasminogen activator. These data provide functional evidence that Rab27A acts as a novel mediator of invasion and metastasis promotion in human breast cancer cells, at least in part, through regulating the secretion of IGF-II, suggesting that synergistic suppression of Rab27A and IGF-II activities holds a promise for preventing breast cancer invasion and metastasis. (Mol Cancer Res 2008;6(3):372–82)
Geldanamycin-Induced Down-Regulation of ErbB2 from the Plasma Membrane Is Clathrin Dependent but Proteasomal Activity Independent
Authors: Pedersen Nina Marie , Madshus Inger Helene , Haslekås Camilla , Stang Espen
Published: March 2008

ErbB2, a member of the epidermal growth factor receptor family, is overexpressed in a number of human cancers. In contrast to the epidermal growth factor receptor, ErbB2 is normally endocytosis resistant. However, ErbB2 can be down-regulated by inhibitors of heat shock protein 90, such as geldanamycin. We now show that geldanamycin induces endocytosis and lysosomal degradation of full-length ErbB2. We further report that the endocytosis of ErbB2 is dynamin and clathrin dependent. When ErbB2 was retained at the plasma membrane due to knockdown of clathrin heavy chain, the intracellular part of ErbB2 was degraded in a proteasomal manner. However, our data strongly suggest that proteasomal activity is not required for geldanamycin-induced endocytosis of ErbB2 in SKBr3 cells. Interestingly, however, proteasomal inhibitors retarded degradation of ErbB2, and electron microscopy analysis strongly suggested that proteasomal activity is required to sort internalized ErbB2 to lysosomes. Because geldanamycin derivatives and inhibitors of proteasomal activity are both used in experimental cancer treatment, knowledge of molecular mechanisms involved in geldanamycin-induced down-regulation of ErbB2 is important for future design of cancer treatment. (Mol Cancer Res 2008;6(3):491–500)
Glioma Regression In vitro and In vivo by a Suicide Combined Treatment
Authors: García-Escudero Vega , Gargini Ricardo , Izquierdo Marta
Published: March 2008

We present here a suicide therapy against malignant gliomas based on the transfer to tumor cells of a gene encoding a β-glucosidase, linamarase (lis), which in the presence of the innocuous substrate linamarin (lin) produces cyanide, blocking the mitochondrial respiratory chain. Dog glioma cells carrying the lis gene are thus sensitive to lin (IC50 of 250 μg/mL at 48 hours) and cell death is accompanied by mitochondrial fission and ATP depletion. The combination of lis/lin with an otherwise nontoxic level of glucose oxidase (GO) enhances the therapeutic potential (IC50 of 50 μg/mL at 48 hours). GO produces hydrogen peroxide, inducing oxidative damage and increasing cellular stress. We show here the antitumoral effect of the lis/lin/GO therapy in a canine glioma cell line and in a xenograft glioma model in nude mice. The synergic combination causes mitochondrial membrane depolarization and phosphatidylserine externalization and accelerates death by 48 hours. The lethal process is caspase independent; poly(ADP-ribose) polymerase 1 is not implicated; and there is no apoptosis-inducing factor translocation to the nucleus. The combined system induces autophagic cell death that can be rescued by 3-methyladenine and is characterized by the presence of double-membrane vesicles and punctate LC-3 pattern. (Mol Cancer Res 2008;6(3):407–17)
Epidermal Growth Factor Receptor vIII Expression in U87 Glioblastoma Cells Alters Their Proteasome Composition, Function, and Response to Irradiation
Authors: Kim Kwanghee , Brush James M. , Watson Philip A. , Cacalano Nicholas A. , Iwamoto Keisuke S. , McBride William H.
Published: March 2008

Little is known about the factors that influence the proteasome structures in cells and their activity, although this could be highly relevant to cancer therapy. We have previously shown that, within minutes, irradiation inhibits substrate degradation by the 26S proteasome in most cell types. Here, we report an exception in U87 glioblastoma cells transduced to express the epidermal growth factor receptor vIII (EGFRvIII) mutant (U87EGFRvIII), which does not respond to irradiation with 26S proteasome inhibition. This was assessed using either a fluorogenic substrate or a reporter gene, the ornithine decarboxylase degron fused to ZsGreen (cODCZsGreen), which targets the protein to the 26S proteasome. To elucidate whether this was due to alterations in proteasome composition, we used quantitative reverse transcription-PCR to quantify the constitutive (X, Y, Z) and inducible 20S subunits (Lmp7, Lmp2, Mecl1), and 11S (PA28α and β) and 19S components (PSMC1 and PSMD4). U87 and U87EGFRvIII significantly differed in expression of proteasome subunits, and in particular immunosubunits. Interestingly, 2 Gy irradiation of U87 increased subunit expression levels by 16% to 324% at 6 hours, with a coincident 30% decrease in levels of the proteasome substrate c-myc, whereas they changed little in U87EGFRvIII. Responses similar to 2 Gy were seen in U87 treated with a proteasome inhibitor, NPI0052, suggesting that proteasome inhibition induced replacement of subunits independent of the means of inhibition. Our data clearly indicate that the composition and function of the 26S proteasome can be changed by expression of the EGFRvIII. How this relates to the increased radioresistance associated with this cell line remains to be established. (Mol Cancer Res 2008;6(3):426–34)
The Critical Role of the Colony-Stimulating Factor-1 Receptor in the Differentiation of Myeloblastic Leukemia Cells
Authors: Hamilton John A. , Whitty Genevieve , Masendycz Paul , Wilson Nicholas J. , Jackson Jacob , De Nardo Dominic , Scholz Glen M.
Published: March 2008

How diverse stimuli control hemopoietic lineage development is unknown. An early event during induction of macrophage differentiation in the myeloblastic leukemia M1 cell line by different stimuli, such as leukemia inhibitory factor (LIF) and interleukin-6 (IL-6), is expression of the colony-stimulating factor-1 receptor (CSF-1R). We report that expression of active CSF-1R in M1 cells accelerated their subsequent terminal differentiation into macrophages in response to LIF and IL-6 when compared with cells lacking the CSF-1R or expressing the receptor with compromised kinase activity; however, there was no requirement for signaling through the CSF-1R, for example, via endogenous CSF-1, during the actual LIF-induced and IL-6–induced differentiation stage. Differences were noted in the signaling pathways downstream of the LIF receptor depending on the presence of the CSF-1R. Both LIF and IL-6 gave an additive response with CSF-1, consistent with LIF and IL-6 acting via a different signaling pathway (signal transducer and activator of transcription 3 dependent) than CSF-1 (extracellular signal-regulated kinase dependent). Based at least on this cell model, we propose that terminal macrophage differentiation involves a critical priming or deterministic phase in which signaling by the CSF-1R prepares a precursor population for subsequent rapid terminal macrophage differentiation by diverse stimuli. We also propose that expression and activation of the CSF-1R explain much prior literature on macrophage lineage commitment in M1 leukemic cells and may be important in controlling the progression of certain myeloid leukemias. (Mol Cancer Res 2008;6(3):458–67)
Cripto-1 Alters Keratinocyte Differentiation via Blockade of Transforming Growth Factor-β1 Signaling: Role in Skin Carcinogenesis
Authors: Shukla Anjali , Ho Yan , Liu Xin , Ryscavage Andrew , Glick Adam B.
Published: March 2008

Cripto-1 is an epidermal growth factor-Cripto/FRL1/Cryptic family member that plays a role in early embryogenesis as a coreceptor for Nodal and is overexpressed in human tumors. Here we report that in the two-stage mouse skin carcinogenesis model, Cripto-1 is highly up-regulated in tumor promoter–treated normal skin and in benign papillomas. Treatment of primary mouse keratinocytes with Cripto-1 stimulated proliferation and induced expression of keratin 8 but blocked induction of the normal epidermal differentiation marker keratin 1, changes that are hallmarks of tumor progression in squamous cancer. Chemical or genetic blockade of the transforming growth factor (TGF)-β1 signaling pathway using the ALK5 kinase inhibitor SB431542 and dominant negative TGF-β type II receptor, respectively, had similar effects on keratinocyte differentiation. Our results show that Cripto-1 could block TGF-β1 receptor binding, phosphorylation of Smad2 and Smad3, TGF-β–responsive luciferase reporter activity, and TGF-β1–mediated senescence of keratinocytes. We suggest that inhibition of TGF-β1 by Cripto-1 may play an important role in altering the differentiation state of keratinocytes and promoting outgrowth of squamous tumors in the mouse epidermis. (Mol Cancer Res 2008;6(3):509–16)
Spreading or Concentrating Drinking Occasions – Who Is Most at Risk?
Authors: Kuntsche Sandra , Plant Moira L. , Plant Martin A. , Miller Patrick , Gmel Gerhard
Published: March 2008

Aims: (a) To compare acute negative consequences for people who drink a given amount of alcohol on few occasions (concentrators) per week in comparison with the consequences for people who drink the same amount on more days in a week (spreaders). (b) To investigate whether these associations are cross-culturally stable. Methods: Analysis is based on general population surveys of adults conducted in 7 European countries. Results: It appeared that more drinking occasions in many countries lead to more consequences independent of the volume consumed. Risky single-occasion drinking was to be associated with higher risks for immediate health consequences and legal problems, accidents and fights. Among older respondents the same frequency pattern appeared, with the exception of immediate health consequences among women. Hence, more regular drinking seemed to have more beneficial effects on older individuals compared to younger ones, which may be related to the different drinking situation: younger people mostly drinking outside the home. Amongst the younger people, frequent drinking seemed to be associated with more acute consequences. Cultural and methodological variations must be taken into account. Conclusion: Even so, it is concluded that the credibility of these findings is strengthened by differences in the methods of the surveys.
Quality of Life in Patients Receiving Opioid Maintenance Therapy
Authors: Winklbaur Bernadette , Jagsch Reinhold , Ebner Nina , Thau Kenneth , Fischer Gabriele
Published: March 2008

Background/Aims: In recent years, quality of life (QoL) assessments have proved useful for evaluating and comparing drug treatment programs. To compare QoL of patients maintained on methadone versus slow-release morphine, a prospective, randomized, double-blind, double-dummy, cross-over study was conducted. Methods: Over two 7-week study phases, participants received either oral slow-release morphine capsules followed by methadone oral solution or vice versa. QoL status was assessed at baseline, week 7, and week 14 using the German version of the Lancashire Quality of Life Profile. Results: No statistically significant difference was found between methadone and slow-release morphine in any QoL domain. A significant time effect for nearly all QoL domains was observed after 14 weeks of opioid medication, independent of the chosen drug (general well-being, p < 0.001; mental health, p = 0.001; general state of health, p = 0.018; leisure time at home, p = 0.034; leisure time out of the home, p = 0.008). Furthermore, this study revealed that even short-term maintenance yields significantly higher QoL scores in the important domain of general well-being. Conclusion: These results indicate that slow-release morphine has effects comparable to methadone on patient-reported QoL data and is thus a promising option for treatment of opioid-dependent subjects.
Partner Effects and Bidirectional Parent-Child Effects in Family Alcohol Use
Authors: Otten Roy , van der Zwaluw Carmen S. , van der Vorst Haske , Engels Rutger C.M.E.
Published: March 2008

Introduction: The current study investigated partner effects and bidirectional parent-child effects in family alcohol use. Methods: A full family, longitudinal design was used to test the hypotheses. Participants were 428 families, including mothers, fathers, and 2 children. Associations were measured over two waves with a 2-year interval, by means of structural equation modeling. Results: Whereas alcohol use of the younger children was affected by alcohol use of both parents, alcohol use of the older children was only affected by alcohol use of mother. Moreover, although the effects were small, alcohol use of older children affected later alcohol use of both parents. Conclusions: Associations between alcohol use of parents and children seem to be bidirectional. Future studies are needed to find out whether these findings are incidental or structural. If the effects are structural, potential underlying reciprocal processes within the family play a role in the development of adolescent alcohol use.
Pregnancy and Birth under Maintenance Treatment with Diamorphine (Heroin): A Case Report
Authors: Hartwig Christina , Haasen Christian , Reimer Jens , Garbe Werner , Lichtermann Dirk , Wuellenweber Linde , Dilg Christoph
Published: March 2008

Background: Heroin-assisted treatment (HAT) is a new form of treatment for heroin-dependent patients not responding to conventional interventions such as methadone maintenance treatment. No pregnancies or births under HAT have been reported until now. Case: The pregnancy course of a 31-year-old severely dependent multi-morbid woman receiving HAT and the birth of a healthy baby after premature delivery is described. HAT helped to reduce the use of illicit substances both before and during pregnancy. The neonatal abstinence syndrome was clinically well compensated. Conclusion: HAT seems to be feasible in pregnant women and normal birth is possible under HAT, which therefore may act as a harm reduction measure for polydrug-using pregnant women not responding to methadone maintenance treatment.
Do Different Disorders in Cell Cycle Regulation Account for Different Biological Behavior of Urothelial and Sinonasal Inverted Papillomas?
Authors: Gunia S. , Fritzsche F. , May M. , Liebe D. , Koch S.
Published: March 2008

Objective: It was the aim of this study to assess the expression of selected cell cycle regulation genes in urothelial and sinonasal inverted papillomas (IP). Methods: Archived surgically resected specimens from 18 urothelial and 19 sinonasal IP were studied immunohistochemically for p16, p53, cyclin D1 and Ki67. Staining results were semiquantified and compared between IP and adjacent control mucosa (CM). Results: p53 expression did not differ between sinonasal and urothelial IP. Although there was a trend of higher p53 expression in IP compared with the adjacent CM in sinonasal and urothelial specimens, this trend failed to be statistically significant. p16 expression was significantly higher in urothelial IP and CM in comparison with their sinonasal counterparts, but did not differ significantly between IP and its adjacent CM either in urothelial or sinonasal specimens. There were no significant differences in the mean scores for cyclin D1 or Ki67. Conclusion: The changes in p53 expression seen in both types of IP compared with adjacent CM suggest that sinonasal and urothelial IP may share some common ground in terms of their evolution. Although p16 appears not to be directly involved in the development of sinonasal or urothelial IP, the differing recurrence patterns of sinonasal versus urothelial IP may be attributable in part to different p16 expression.
Incidence and Prevalence of Amyotrophic Lateral Sclerosis in Uruguay: A Population-Based Study
Authors: Vázquez M.C. , Ketzoián C. , Legnani C. , Rega I. , Sánchez N. , Perna A. , Penela M. , Aguirrezábal X. , Druet-Cabanac M. , Medici M.
Published: March 2008

Objective: To determine the incidence and prevalence of amyotrophic lateral sclerosis (ALS) in the Republic of Uruguay.Methods: The study was performed in Uruguay (3,241,003 inhabitants) during a 2-year period (2002–2003). To ensure complete case ascertainment, multiple sources of information were used, including all the neurologists, other medical specialties, general physicians, neurophysiology laboratories, hospital medical records and death certificates. ALS diagnosis was based on El Escorial criteria. Although all patients with motor neuron disease were enrolled in the follow-up, only probable and definite cases are included in the study. Results: Between January 1st, 2002, and December 31st, 2003, 89 new patients were diagnosed with probable or definite ALS. The mean annual incidence rate was 1.37 per 100,000 persons. The incidence was higher for men (1.95) than for women (0.84) with a male to female ratio of 2:1. For both, the incidence increased throughout the years showing a peak in the 65–74 age group among men and the 55–64 age group among women. Mean age at onset of ALS disease was 58.7 years. The estimated mean annual incidence for ALS calculated by the capture recapture method was 1.42 (95% CI, 1.13–1.72). On December 31st, 2002, the crude prevalence was 1.9 per 100,000 inhabitants. Conclusions: ALS incidence is within a narrow range across countries despite the genetic, environmental and socioeconomic differences when similar prospective design, diagnosis criteria and data analyses are applied.
Diagnosis and Management of Large Occipitocervical Cephaloceles: A 10-Year Experience
Authors: Kotil Kadir , Kilinc Bekir , Bilge Turgay
Published: March 2008

Background/Aims: Cephaloceles are common malformations of the central nervous system. However, the great majority of clinical experiences in large occipitocervical cephaloceles have not been reported previously. The purpose of this report is to investigate the pathogenetic factors involved in the development of cranial dysraphism and to analyze the clinical and pathological factors that influence the outcome in patients. Methods: Three hundred and twenty infants with craniospinal dysraphism and 12 with large occipitocervical cephaloceles were admitted to our institution in a 10-year interval between 1995 and 2005. Infants with cephaloceles, including newborns and 5 within the first year of life, were all operated by two authors in our institution, and they were analyzed retrospectively. Results: The sex predilection was limited to occipitocervical cephaloceles, where 8 of the 12 cases were females. Hydrocephalus was present in 25% of the patients at the time of diagnosis. Clinical presentation was most often consistent with hydrocephalus, focal neurological findings being a less prominent feature. Associated congenital anomalies were present in 50% of the children. Contemporary neuroimaging techniques including computed tomography and magnetic resonance imaging facilitated the diagnosis. Patients were initially managed by posterior fossa or cervical region exploration, followed by sac excision. Three cases died in the early postoperative period, and the surgical mortality in this series was 25%. They were the ones with the largest encephaloceles and microcephaly. The mean follow-up time was 3.4 years. The overall mortality rate for the whole series was 33.3% (4/12). The size of the cephaloceles and the presence or absence of neural tissue in the sac largely determines the outcome for patients with occipitocervical cephaloceles. Conclusion: Infants with lesions greater than 50 mm in diameter, containing a significant amount of neural tissue, have an extremely poor prognosis, especially if associated with microcephaly.
Surgery without Assistance in Newborns and Infants with Hydrocephalus and Neural Tube Defects
Authors: Mauer U.M. , King’ori C. , Hummler H. , Kunz U.
Published: March 2008

Standard neurosurgical procedures for hydrocephalus and open neural tube defects in newborns and infants under 6 months of age were performed by a single neurosurgeon on his own without the help of an assistant or scrub nurse. The objective of this study was to assess the outcome of these procedures in terms of operating time, the presence of bacterial infection, and wound healing. Between 2001 and 2004, a total of 126 procedures were performed on 82 patients under 6 months of age. We observed 1 bacterial and 2 fungal infections. Two infections had already been detected at the beginning of the surgical procedure in cerebrospinal fluid (CSF) specimens obtained from children with Candida ventriculitis. The other infection occurred after leakage of CSF from a myelomeningocele 10 days after initial surgery. Our study suggests that excellent results can be achieved in standard neurosurgical procedures without assistance even in high-risk newborns and infants if resource or other constraints require such an unconventional approach.
Clinical Cases where Lesion Therapy Was Chosen over Deep Brain Stimulation
Authors: Hooper Amanda K. , Okun Michael S. , Foote Kelly D. , Fernandez Hubert H. , Jacobson Charles , Zeilman Pamela , Romrell Janet , Rodriguez Ramon L.
Published: March 2008

Deep brain stimulation (DBS) surgery has become the gold standard for treatment of select refractory cases of Parkinson disease and essential tremor. Despite the usefulness of DBS surgery in many cases, there remain situations where lesion therapy (subthalamotomy, pallidotomy or thalamotomy) may provide a reasonable alternative to DBS. We reviewed the University of Florida Institutional Review Board-approved database for movement disorders surgery and identified 286 DBS leads placed in 189 patients as well as 4 additional patients who had lesion therapy. In these 4 cases we reviewed the clinical presentations that resulted in a multidisciplinary team opting for lesion therapy over DBS. Lesion therapy represents a viable alternative and has several important advantages, including a decreased need for access to specialists and clinical follow-up, improved affordability, and a lower infection risk.
CYR61 Downregulation Correlates with Tumor Progression by Promoting MMP-7 Expression in Human Gastric Carcinoma
Authors: Maeta Noritaka , Osaki Mitsuhiko , Shomori Kohei , Inaba Aiko , Kidani Kazunori , Ikeguchi Masahide , Ito Hisao
Published: March 2008

Objective: CYR61 (cysteine-rich 61) belongs to the CCN (CYR61/CTGF/NOV) protein family and is involved in tumorigenesis. We have previously confirmed that the level of CYR61 protein is decreased in gastric carcinoma compared with nontumoral mucosa, by conducting proteome-based analyses. In this study, we examine the relationship between CYR61 expression and clinicopathological data of MMP-7 expression in human gastric mucosae and tumors. Methods: Immunohistochemical and/or immunofluorescence analyses were performed to examine the histological expression of CYR61 in normal gastric mucosa, intestinal metaplasia, 33 adenomas, and 127 carcinomas. Seven gastric carcinoma cell lines were used to examine the expression of CYR61 and MMP-7 by Western blotting. Results: The CYR61-expressing cells mostly coincided with the serotonin-containing cells, not only in nontumoral epithelia, but also among tumor cells. CYR61 expression was positive (labeling index: >2%) in 43 of 49 early gastric carcinomas (87.8%) and in 19 of 78 advanced gastric carcinomas (24.4%), the frequency being significantly lower in the latter (p < 0.001). All the normal mucosae, intestinal metaplasias and adenomas were in the positive group. The reduction in CYR61 expression correlated significantly with histological differentiation (p < 0.05), depth of invasion (p < 0.001), lymphatic invasion (p < 0.001), venous invasion (p < 0.001), lymph node metastasis (p < 0.001) and clinical stage (p < 0.001). Immunohistochemistry and Western blotting revealed the expression of CYR61 to be inversely correlated with that of MMP-7 (p < 0.001). Conclusions: CYR61 is expressed in serotonin-containing cells, and downregulation of the expression might contribute to the progression of cancer by promoting MMP-7 expression in human gastric carcinomas.
Increased Susceptibility to Oxidant-Mediated Tissue Injury and Peritoneal Fibrosis in Acatalasemic Mice
Authors: Fukuoka Naomi , Sugiyama Hitoshi , Inoue Tatsuyuki , Kikumoto Yoko , Takiue Kei-ichi , Morinaga Hiroshi , Nakao Kazushi , Maeshima Yohei , Asanuma Masato , Wang Da-Hong , Ogino Keiki , Masuoka Noriyoshi , Makino Hirofumi
Published: March 2008

Background: Peritoneal fibrosis is a major complication leading to the loss of peritoneal function in patients undergoing peritoneal dialysis. However, the effect of catalase depletion on peritoneal fibrosis has not yet been investigated. Methods: The impact of catalase deficiency on progressive peritoneal fibrosis has been studied in homozygous acatalasemic mutant mice or control wild-type mice by intraperitoneal injection of chlorhexidine gluconate (CG) every other day for 14 days. Results: The CG injections resulted in a thicker peritoneal membrane, reflecting peritoneal fibrosis with accumulation of interstitial type I collagen, peritoneal deposition of lipid peroxidation products (4-hydroxy-2-nonenal and 4-hydroxy-2-hexenal), and an elevated level of 8-hydroxy-2′-deoxyguanosine in peritoneal fluid in both mouse groups on day 14. The extent of these changes, however, was significantly higher in acatalasemic mice than in wild-type mice. The level of catalase activity remained low in the acatalasemic peritoneum without the compensatory upregulation of glutathione peroxidase, but with an insufficient upregulation of superoxide dismutase activity in CG-injected mice. Conclusions: Acatalasemia, therefore, exacerbates oxidant tissue injury and induces the peritoneum to develop irreversible fibrosis which is the most important complication of peritoneal dialysis. This study suggests that catalase plays a crucial role in the defense against oxidant-mediated peritoneal injury in a mouse peritoneal fibrosis model.
Is Fetuin-A/α2-Heremans-Schmid Glycoprotein Associated with the Metabolic Syndrome in Patients with Chronic Kidney Disease?
Authors: Axelsson Jonas , Wang Xin , Ketteler Markus , Qureshi Abdul Rashid , Heimbürger Olof , Bárány Peter , Lindholm Bengt , Nordfors Louise , Stenvinkel Peter
Published: March 2008

Introduction: Components of the metabolic syndrome are highly prevalent in chronic kidney disease (CKD) patients – some of which paradoxically appear to predict an improved outcome in this population. We hypothesized that the circulating calcification inhibitor fetuin-A/AHSG, which is also a natural inhibitor of the tyrosine kinase insulin receptor, could be one factor explaining the association between increased fat mass and a survival advantage in CKD and thus conducted an explorational study to provide preliminary data to support further research into this hypothesis. Patients and Methods: In a cross-sectional study, we evaluated 198 CKD stage 5 patients (GFR 6.8 ± 0.2 ml/min; 62% males, mean age 52 ± 1 years) close to the start of renal replacement therapy. We studied circulating AHSG (ELISA) and two common functional AHSG gene polymorphisms (at amino acids Thr248Met (C-T) and Thr256Ser (C-G) using Pyrosequencing®) and related these to multiple components of the metabolic syndrome. Results: Median circulating AHSG was lower (p < 0.01) in type-2 (0.22 g/l) and type-1 (0.16 g/l) diabetics as compared to non-diabetic CKD-5 patients (0.24 g/l). AHSG correlated with both total and truncal fat mass in type-2 diabetics (rho 0.37 and 0.39; p < 0.001, respectively), but not in type-1 diabetics or non-diabetics. Both SNPs significantly influenced circulating levels of AHSG, and were also associated with significant differences in serum triglycerides and HDL cholesterol. Furthermore, there were significant differences in the prevalence of metabolic syndrome criteria between the AHSG Thr256Ser (C-G) genotype groups, with a more atherogenic lipid profile in AHSG high producers (Thr/Thr homozygotes). In multivariate analysis, the association between circulating AHSG and fat mass remained significant also after adjustment for age, gender, inflammation (CRP >10 mg/l), and AHSG genotype. Conclusions: The present, explorational, study supports further, mechanistic, studies into a physiological link between AHSG and body fat mass in patients with CKD. As we observed an association between higher fat mass and elevated AHSG levels, these preliminary results may form the basis of further study to establish if the observed associations may be one reason why obesity has been reported to constitute a survival advantage in CKD.
Adaptive Integration in the Visual Cortex by Depressing Recurrent Cortical Circuits
Authors: van Rossum Mark C. W. , van der Meer Matthijs A. A. , Xiao Dengke , Oram Mike W.
Published: March 2008

Neurons in the visual cortex receive a large amount of input from recurrent connections, yet the functional role of these connections remains unclear. Here we explore networks with strong recurrence in a computational model and show that short-term depression of the synapses in the recurrent loops implements an adaptive filter. This allows the visual system to respond reliably to deteriorated stimuli yet quickly to high-quality stimuli. For low-contrast stimuli, the model predicts long response latencies, whereas latencies are short for high-contrast stimuli. This is consistent with physiological data showing that in higher visual areas, latencies can increase more than 100 ms at low contrast compared to high contrast. Moreover, when presented with briefly flashed stimuli, the model predicts stereotypical responses that outlast the stimulus, again consistent with physiological findings. The adaptive properties of the model suggest that the abundant recurrent connections found in visual cortex serve to adapt the network's time constant in accordance with the stimulus and normalizes neuronal signals such that processing is as fast as possible while maintaining reliability.
Good Career Moves: Life Stories of Daoist Nuns of the Twelfth and Thirteenth Centuries
Authors: Chao Shin-yi
Published: March 2008

Daoist monasticism rose to prominence in China during the late twelfth and the mid-thirteenth centuries amid the turmoil of war and dynastic change. A particular Daoist monastic order emerged, called Quanzhen or 'Complete Perfection', which became popular and spread throughout China. A number of commemorative stone steles from the monasteries of the period have been preserved, and serve as the main sources for this article. The steles record the religious activities and experiences of female practitioners, some of whom rose to leading positions, as founders, abbesses, and managers of flourishing monasteries. The funding for these monasteries came from the donations of the lay followers whom they inspired. Within the monastic universe, they trained and ordained the next generation of clerics, and provided ritual services to the lay community as well. Toward the end of their careers, abbesses choose their successors from among their female disciples, and a lineage based on the master-disciple relationship took shape.
Kritische Bemerkungen zur Geschichte der religiösen Toleranz und zur Tradition der Lessing'schen Ringparabel
Authors: Dinzelbacher Peter
Published: March 2008

Although the medieval tradition of the famous parable which stands in the centre of Lessing's Nathan der Weise is quite well known, the present writer holds that the older versions of this motive are usually misinterpreted, being habitually read in the light of the German poet's text written during the age of enlightenment. An analysis, however, of the original stories of Etienne de Bourbon, Busone, Boccaccio et al., shows that their real aim was to illustrate an aporia and the shrewdness necessary to escape from it, not to call for religious tolerance. Indeed, the latter idea grew out of the disasters of the Thirty Years' War only, and was nearly completely alien to the Middle Ages. The few exceptions (Wolfram von Eschenbach, Ramon Llull, Nicolaus Cusanus) — and their limitations — are briefly discussed.
The Cilician God Sandas and the Greek Chimaera: Features of Near Eastern and Greek Mythology Concerning the Plague
Authors: Mastrocinque Attilio
Published: March 2008

A gem in the Museum of Castelvecchio (Verona) depicts the god Sandas of Tarsos with his terrible animal: the lion-goat. On the reverse side there is the inscription YOYO. The epigraphical and archaeological evidence from Anatolia, from Hittite to Hellenistic times, proves that Sandas was a underworld god protecting tombs and sending pestilences when angry. He was appeased by offerings to his terrible ministers, who were usually seven. Similarly Nergal or Erra (similar to Sandas) in Mesopotamia, and Sekhmet in Egypt had seven animal-headed terrible ministers, who were able to bring pestilences and death. A Hittite inscription mentions Yaya as Sandas' female partner. Her name is very similar to the Yoyo on the Verona gem. Sandas was identified with Heracles because of his relations with the underworld realms and his warlike features. The lion-goat of Tarsus was the model of Greek Chimaera. In fact the myth of Bellerophon took its place in Lycia and Cilicia. In Hellenistic age the original form of this monster was better known and therefore we find its typical features in Hellenistic and Roman sculptures and reliefs.
The First Documented Occurence of the God Yahweh? (Book of the Dead Princeton “Roll 5”)
Authors: Schneider Thomas
Published: March 2008

The article presents and discusses the proper name of the owner of a recently unfolded and mounted Book of the Dead papyrus from the late 18th or 19th dynasty (Princeton University Library, Pharaonic Roll 5). It is proposed that the name in question is a Northwest Semitic theophoric sentence name in Egyptian transcription, 'adōnī-rō'ē-yāh “My lord is the shepherd of Yah”. Whereas the name Yahweh has been known from Egyptian toponym lists of the New Kingdom, the present name would be the first documented occurence of the god Yahweh in his function as a shepherd of Yah, the short form of the tetragrammaton. The article also points to a new etymology of the divine name and the cultural significance of the evidence.
Serbo-Croatian Influences on Bosnian Spoken Judeo-Spanish
Authors: Papo Eliezer
Published: March 2008

The sweeping and far-reaching political, economical and demographical changes in Bosnia and Herzegovina at the end of 19th, beginning of the 20th century affected profoundly the linguistic situation of the country's Jewish, overwhelmingly Sephardic, minority. Having lost the unity with their brethren on Balkans, the Bosnian Jews had to rely more and more on their relations with other Bosnian ethno-religious communities. It is from this deepened contact with their Serbian, Muslim and Croatian neighbors on one side and from the constant need for new linguistic solutions, brought about by the ever changing reality, that Serbo-Croatian influences (once so superficial) started entering all the spheres of Bosnian Judeo-Spanish, its lexicon, morphology, phonology, syntax, and even grammar. The author analyzes those influences as they are, consciously or unconsciously, reflected in the literature produced by the members of the Sephardic Circle—the Sarajevo-based group of young and idealistic Sephardic intellectuals who tried to fight and prevent the oblivion of Judeo-Spanish language and culture.