bluuebunny/crossref_metadata_2025 huggingface dataset:
Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis
Authors: Bråkenhielm Ebba , Veitonmäki Niina , Cao Renhai , Kihara Shinji , Matsuzawa Yuji , Zhivotovsky Boris , Funahashi Tohru , Cao Yihai
Published: February 2004

Obesity is a risk factor for the development of many severe human diseases such as cardiovascular disorders, diabetes, and cancer, which are tightly linked to angiogenesis. The adipose tissue produces several growth factors/hormones including leptin, tumor necrosis factor α, and adiponectin. It has been found that adiponectin levels are reduced in obesity. Here, we report a unique function of adiponectin as a negative regulator of angiogenesis.
In vitro
, adiponectin potently inhibits endothelial cell proliferation and migration. In the chick chorioallantoic membrane and the mouse corneal angiogenesis assays, adiponectin remarkably prevents new blood vessel growth. Further, we demonstrate that the antiendothelial mechanisms involve activation of caspase-mediated endothelial cell apoptosis. Adiponectin induces a cascade activation of caspases-8, -9, and -3, which leads to cell death. In a mouse tumor model, adiponectin significantly inhibits primary tumor growth. Impaired tumor growth is associated with decreased neovascularization, leading to significantly increased tumor cell apoptosis. These data demonstrate induction of endothelial apoptosis as an unique mechanism of adiponectin-induced antiangiogenesis. Adiponectin, as a direct endogenous angiogenesis inhibitor, may have therapeutic implications in the treatment of angiogenesis-dependent diseases.
Multiple sclerosis: Brain-infiltrating CD8+T cells persist as clonal expansions in the cerebrospinal fluid and blood
Authors: Skulina Christian , Schmidt Stephan , Dornmair Klaus , Babbe Holger , Roers Axel , Rajewsky Klaus , Wekerle Hartmut , Hohlfeld Reinhard , Goebels Norbert
Published: February 2004

We surveyed the T cell receptor repertoire in three separate compartments (brain, cerebrospinal fluid, and blood) of two multiple sclerosis patients who initially had diagnostic brain biopsies to clarify their unusual clinical presentation but were subsequently confirmed to have typical multiple sclerosis. One of the brain biopsy specimens had been previously investigated by microdissection and single-cell PCR to determine the clonal composition of brain-infiltrating T cells at the single-cell level. Using complementarity-determining region 3 spectratyping, we identified several identical, expanded CD8+(but not CD4+) T cell clones in all three compartments. Some of the expanded CD8+T cells also occurred in sorted CD38+blood cells, suggesting that they were activated. Strikingly, some of the brain-infiltrating CD8+T cell clones persisted for >5 years in the cerebrospinal fluid and/or blood and may thus contribute to the progression of the disease.
Tomosyn inhibits priming of large dense-core vesicles in a calcium-dependent manner
Authors: Yizhar Ofer , Matti Ulf , Melamed Rely , Hagalili Yamit , Bruns Dieter , Rettig Jens , Ashery Uri
Published: February 2004

Neurotransmitter release is a multistep process that is coordinated by a large number of synaptic proteins and depends on proper protein–protein interactions. Using morphological, capacitance, and amperometric measurements, we investigated the effect of tomosyn, a Syntaxin-binding protein, on the different kinetic components of exocytosis in adrenal chromaffin cells. Overexpression of tomosyn decreased the release probability and led to a 50% reduction in the number of fusion-competent vesicles. The number of docked vesicles and the fusion kinetics of single vesicles were not altered suggesting that tomosyn inhibits the priming step. Interestingly, this inhibition is partially relieved at elevated calcium concentration. Calcium ramp experiments supported the latter finding and indicated that the reduction in secretion is caused by a shift in the calcium-dependence of release. These results indicate that secretion is not entirely blocked but occurs at higher calcium concentrations. We suggest that tomosyn inhibits the priming step and impairs the efficiency of vesicle pool refilling in a calcium-dependent manner.
The precursor form of IL-1α is an intracrine proinflammatory activator of transcription
Authors: Werman Ariel , Werman-Venkert Rachel , White Rosalyn , Lee Jae-Kwon , Werman Batsheva , Krelin Yakov , Voronov Elena , Dinarello Charles A. , Apte Ron N.
Published: February 2004

Although most cytokines are studied for biological effects after engagement of their specific cell surface membrane receptors, increasing evidence suggests that some function in the nucleus. In the present study, the precursor form of IL-1α was overexpressed in various cells and assessed for activity in the presence of saturating concentrations of IL-1 receptor antagonist to prevent receptor signaling. Initially diffusely present in the cytoplasm of resting cells, IL-1α translocated to the to nucleus after activation by endotoxin, a Toll-like receptor ligand. The IL-1α precursor, but not the C-terminal mature form, activated the transcriptional machinery in the GAL4 system by 90-fold; a 50-fold increase was observed using only the IL-1α propiece, suggesting that transcriptional activation was localized to the N terminus where the nuclear localization sequence resides. Under conditions of IL-1 receptor blockade, intracellular overexpression of the precursor and propiece forms of IL-1α were sufficient to activate NF-κB and AP-1. Stable transfectants overproducing precursor IL-1α released the cytokines IL-8 and IL-6 but also exhibited a significantly lower threshold of activation to subpicomolar concentrations of tumor necrosis factor α or IFN-γ. Thus, intracellular functions of IL-1α might play an unforeseen role in the genesis of inflammation. During disease-driven events, the cytosolic precursor moves to the nucleus, where it augments transcription of proinflammatory genes. Because this mechanism of action is not affected by extracellular inhibitors, reducing intracellular functions of IL-1α might prove beneficial in some inflammatory conditions.
Association between climate variability and malaria epidemics in the East African highlands
Authors: Zhou Guofa , Minakawa Noboru , Githeko Andrew K. , Yan Guiyun
Published: February 2004

The causes of the recent reemergence of
Plasmodium falciparum
epidemic malaria in the East African highlands are controversial. Regional climate changes have been invoked as a major factor; however, assessing the impact of climate in malaria resurgence is difficult due to high spatial and temporal climate variability and the lack of long-term data series on malaria cases from different sites. Climate variability, defined as short-term fluctuations around the mean climate state, may be epidemiologically more relevant than mean temperature change, but its effects on malaria epidemics have not been rigorously examined. Here we used nonlinear mixed-regression model to investigate the association between autoregression (number of malaria outpatients during the previous time period), seasonality and climate variability, and the number of monthly malaria outpatients of the past 10–20 years in seven highland sites in East Africa. The model explained 65–81% of the variance in the number of monthly malaria outpatients. Nonlinear and synergistic effects of temperature and rainfall on the number of malaria outpatients were found in all seven sites. The net variance in the number of monthly malaria outpatients caused by autoregression and seasonality varied among sites and ranged from 18 to 63% (mean = 38.6%), whereas 12–63% (mean = 36.1%) of variance is attributed to climate variability. Our results suggest that there was a high spatial variation in the sensitivity of malaria outpatient number to climate fluctuations in the highlands, and that climate variability played an important role in initiating malaria epidemics in the East African highlands.
The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations
Authors: Cantor Sharon , Drapkin Ronny , Zhang Fan , Lin Yafang , Han Juliana , Pamidi Sushmita , Livingston David M.
Published: February 2004

BACH1 is a nuclear protein that directly interacts with the highly conserved, C-terminal BRCT repeats of the tumor suppressor, BRCA1. Mutations within the BRCT repeats disrupt the interaction between BRCA1 and BACH1, lead to defects in DNA repair, and result in breast and ovarian cancer. BACH1 is necessary for efficient double-strand break repair in a manner that depends on its association with BRCA1. Moreover, some women with early-onset breast cancer and no abnormalities in either
BRCA1
or
BRCA2
carry germline
BACH1
coding sequence changes, suggesting that abnormal BACH1 function contributes to tumor induction. Here, we show that BACH1 is both a DNA-dependent ATPase and a 5′-to-3′ DNA helicase. In two patients with early-onset breast cancer who carry distinct germline
BACH1
coding sequence changes, the resulting proteins are defective in helicase activity, indicating that these sequence changes disrupt protein function. These results reinforce the notion that mutant BACH1 participates in breast cancer development.
Acetylation of p53 augments its site-specific DNA binding both
in vitro
and
in vivo
Authors: Luo Jianyuan , Li Muyang , Tang Yi , Laszkowska Monika , Roeder Robert G. , Gu Wei
Published: February 2004

p53 promotes tumor suppression through its ability to function as a transcriptional factor and is activated by posttranslational modifications that include acetylation. Our earlier study demonstrated that p53 acetylation can enhance its sequence-specific DNA binding
in vitro
, and this notion was later confirmed in several other studies. However, a recent study has reported that
in vitro
acetylation of p53 fails to stimulate its DNA binding to large DNA fragments, raising an important issue that requires further investigation. Here, we show that unacetylated p53 is able to bind weakly to its consensus site within the context of large DNA fragments, although it completely fails to bind the same site within short oligonucleotide probes. Strikingly, by using highly purified and fully acetylated p53 proteins obtained from cells, we show that acetylation of the C-terminal domain can dramatically enhance site-specific DNA binding on both short oligonucleotide probes and long DNA fragments. Moreover, endogenous p53 apparently can be fully acetylated in response to DNA damage when both histone deacetylase complex 1 (HDAC1)- and Sir2-mediated deacetylation are inhibited, indicating dynamic p53 acetylation and deacetylation events during the DNA damage response. Finally, we also show that acetylation of endogenous p53 indeed significantly augments its ability to bind an endogenous target gene and that p53 acetylation levels correlate well with p53-mediated transcriptional activation
in vivo
. Thus, our results clarify some of the confusion surrounding acetylation-mediated effects on p53 binding to DNA and suggest that acetylation of p53
in vivo
may contribute, at least in part, to its transcriptional activation functions.
PKHD1 protein encoded by the gene for autosomal recessive polycystic kidney disease associates with basal bodies and primary cilia in renal epithelial cells
Authors: Zhang Ming-Zhi , Mai Weiyi , Li Cunxi , Cho Sae-youll , Hao Chuanming , Moeckel Gilbert , Zhao Runxiang , Kim Ingyu , Wang Jikui , Xiong Huaqi , Wang Hong , Sato Yasunori , Wu Yizhong , Nakanuma Yasuni , Lilova Marusia , Pei York , Harris Raymond C. , Li Song , Coffey Robert J. , Sun Le , Wu Dianqing , Chen Xing-Zhen , Breyer Matthew D. , Zhao Zhizhuang Joe , McKanna James A. , Wu Guanqing
Published: February 2004

Mutations of the polycystic kidney and hepatic disease 1 (PKHD1) gene have been shown to cause autosomal recessive polycystic kidney disease (ARPKD), but the cellular functions of the gene product (PKHD1) remain uncharacterized. To illuminate its properties, the spatial and temporal expression patterns of PKHD1 were determined in mouse, rat, and human tissues by using polyclonal Abs and mAbs recognizing various specific regions of the gene product. During embryogenesis, PKHD1 is widely expressed in epithelial derivatives, including neural tubules, gut, pulmonary bronchi, and hepatic cells. In the kidneys of thepckrats, the rat model of which is genetically homologous to human ARPKD, the level of PKHD1 was significantly reduced but not completely absent. In cultured renal cells, thePKHD1gene product colocalized with polycystin-2, the gene product of autosomal dominant polycystic disease type 2, at the basal bodies of primary cilia. Immunoreactive PKHD1 localized predominantly at the apical domain of polarized epithelial cells, suggesting it may be involved in the tubulogenesis and/or maintenance of duct–lumen architecture. Reduced PKHD1 levels inpckrat kidneys and its colocalization with polycystins may underlie the pathogenic basis for cystogenesis in polycystic kidney diseases.
Care reasoning development and family socialisation patterns in later adolescence: A longitudinal analysis
Authors: Pratt Michael W. , Skoe Eva E. , Arnold Mary Louise
Published: February 2004

Over the past 20 years, care reasoning has been increasingly recognised as an important aspect of moral development. Skoe has developed an interview measure of levels of care reasoning about the needs of self and other in relationships, the Ethic of Care Interview or ECI. In the present longitudinal research, we investigated developmental changes and family correlates of reasoning about care issues in a family study of 32 adolescents (aged 16 and then 20 years). There were no gender differences on the ECI for these adolescents, but there was a significant increase in scores over time. Care reasoning levels at age 20 were significant concurrent predictors of self-reported community involvement. Several parenting factors when children were age 16 (parents’ emphasis on caring as a goal in family stories, child reports of a more authoritative family parenting style, and parents’ use of more autonomy-encouraging practices) were associated with higher levels of care reasoning in adolescents at age 20, consistent with theoretical expectations.
Attachment working models as unconscious structures: An experimental test
Authors: Maier Markus A. , Bernier Annie , Pekrun Reinhard , Zimmermann Peter , Grossmann Klaus E.
Published: February 2004

Internal working models of attachment (IWMs) are presumed to be largely unconscious representations of childhood attachment experiences. Several instruments have been developed to assess IWMs; some of them are based on self-report and others on narrative interview techniques. This study investigated the capacity of a self-report measure, the Inventory of Parent and Peer Attachment (IPPA; Armsden & Greenberg, 1987), and of a narrative interview method, the Adult Attachment Interview (AAI; George, Kaplan, & Main, 1985), to measure unconscious attachment models. We compared scores on the two attachment instruments to response latencies in an attachment priming task. It was shown that attachment organisation assessed by the AAI correlates with priming effects, whereas the IPPA scales were inversely or not related to priming. The results are interpreted as support for the assumption that the AAI assesses, to a certain degree, unconscious working models of attachment.
Is Structure Not Enough?
Authors: Votsis Ioannis
Published: February 2004

This paper counters an objection raised against one of Bertrand Russell's lesser-known epistemological views, viz. “structural realism” (SR). In short, SR holds that at most we have knowledge of the structure of the external (i.e., physical) world. M. H. A. Newman's allegedly fatal objection is that SR is either trivial or false. I argue that the accusation of triviality is itself empty since it fails to establish that SR knowledge claims are uninformative. Moreover, appealing to Quine's notion of ontological relativity, I suggest that far from being false, SR knowledge claims seem to be the most that we can hope for.
The Introduction of Information into Neurobiology
Authors: Garson Justin
Published: February 2004

The first use of the term “information” to describe the content of nervous impulse occurs in Edgar Adrian's The Basis of Sensation (1928). What concept of information does Adrian appeal to, and how can it be situated in relation to contemporary philosophical accounts of the notion of information in biology? The answer requires an explication of Adrian's use and an evaluation of its situation in relation to contemporary accounts of semantic information. I suggest that Adrian's concept of information can be to derive a concept of arbitrariness or semioticity in representation. This in turn provides one way of resolving some of the challenges that confront recent attempts in the philosophy of biology to restrict the notion of information to those causal connections that can in some sense be referred to as arbitrary or semiotic.
Affordances Explained
Authors: Scarantino Andrea
Published: February 2004

I examine the central theoretical construct of ecological psychology, the concept of anaffordance.In the first part of the paper, I illustrate the role affordances play in Gibson's theory of perception. In the second part, I argue that affordances are to be understood as dispositional properties, and explain what I take to be their characteristic background circumstances, triggering circumstances and manifestations. The main purpose of my analysis is to give affordances a theoretical identity enriched by Gibson's visionary insight, but independent of the most controversial claims of the Gibsonian movement.
Do You Need to Believe in Orbitals to Use Them?: Realism and the Autonomy of Chemistry
Authors: Jenkins Zack
Published: February 2004

Eric Scerri and other authors have acknowledged that the reality of chemical orbitals is not compatible with quantum mechanics. Recently, however, Scerri and Sharon Crasnow have argued that if chemists cannot consider orbitals as real entities, then chemistry is in danger of being reduced to physics. I argue that the question of the existence of orbitals is best viewed as an issue of explanation, not metaphysics: In many chemically important cases orbitals do not make sufficiently accurate predictions, and must be replaced. Chemists and physicists can acknowledge this fact while maintaining the utility of orbitals and the autonomy of chemistry.
On the Concept of Biological Race and Its Applicability to Humans
Authors: Pigliucci Massimo , Kaplan Jonathan
Published: February 2004

Biological research on race has often been seen as motivated by or lending credence to underlying racist attitudes; in part for this reason, recently philosophers and biologists have gone through great pains to essentially deny the existence of biological human races. We argue that human races, in the biological sense of local populations adapted to particular environments, do in fact exist; such races are best understood through the common ecological concept of ecotypes. However, human ecotypic races do not in general correspond with ‘folk’ racial categories, largely because many similar ecotypes have multiple independent origins. Consequently, while human natural races exist, they have little or nothing in common with ‘folk’ races.
Classical Spontaneous Symmetry Breaking
Authors: Liu Chuang
Published: February 2004

This paper aims at answering the simple question, “What is spontaneous symmetry breaking (SSB) in classical systems?” I attempt to do this by analyzing from a philosophical perspective a simple classical model which exhibits some of the main features of SSB. Related questions include: What does it mean to say that a symmetry is spontaneously broken? Is it broken without any causes, or is the symmetry not broken but merely hidden? Is the principle, “no asymmetry in, no asymmetry out,” violated by SSB? What really distinguishes SSB from the usual types of symmetry breaking?
The Applicability of Shannon Information in Quantum Mechanics and Zeilinger's Foundational Principle
Authors: Timpson Christopher G.
Published: February 2004

Recently, Brukner and Zeilinger have presented a number of arguments suggesting that the Shannon information is not well defined as a measure of information in quantum mechanics. If established, this result would be highly significant, as the Shannon information is fundamental to the way we think about information not only in classical but also in quantum information theory. On consideration, however, these arguments are found unsuccessful; I go on to suggest how they might be arising as a consequence of Zeilinger's proposed foundational principle for quantum mechanics.
Species Pluralism Does Not Imply Species Eliminativism
Authors: Brigandt Ingo
Published: February 2004

Marc Ereshefsky argues that pluralism about species suggests that the species concept is not theoretically useful. It is to be abandoned in favor of several concrete species concepts that denote real categories. While accepting species pluralism, the present paper rejects eliminativism about the species category. Based on the idea that the species concept is a so-called investigative kind concept, it is argued that the species concept is important and that it is possible to make sense of a general species concept despite the existence of different concrete species concepts.
A Matter of Degree: Putting Unitary Inequivalence to Work
Authors: Ruetsche Laura
Published: February 2004

If a classical system has infinitely many degrees of freedom, its Hamiltonian quantization need not be unique up to unitary equivalence. I sketch different approaches (Hilbert space and algebraic) to understanding the content of quantum theories in light of this non-uniqueness, and suggest that neither approach suffices to support explanatory aspirations encountered in the thermodynamic limit of quantum statistical mechanics.
Another No-go Theorem for Hidden Variable Models of Inaccurate Spin 1 Measurements
Authors: Breuer Thomas
Published: February 2004

Uncertainty about the actual orientation of the measurement device has been claimed to open a loophole for hidden variable models of quantum mechanics. In this paper I describe the statistics of inaccurate spin measurements by unsharp spin observables. A no-go theorem for hidden variable models of the inaccurate measurement statistics follows: There is a finite set of directions for which not all results of inaccurate spin measurements can be predetermined in a non-contextual way. In contrast to an earlier theorem (Breuer 2002) this result does not rely on the assigment of approximate truth values, and it holds under weaker assumptions on the measurement inaccuracy.
Remarks on the Direction of Time in Quantum Mechanics
Authors: Hemmo Meir
Published: February 2004

I argue that in the many worlds interpretation of quantum mechanics time has no fundamental direction. I further discuss a way to recover thermodynamics in this interpretation using decoherence theory (Zurek and Paz 1994). Albert's proposal to recover thermodynamics from the collapse theory of Ghirardi et al. (1986) is also considered.
Complex Systems, Trade-Offs, and Theoretical Population Biology: Richard Levin's “Strategy of Model Building in Population Biology” Revisited
Authors: Odenbaugh Jay
Published: February 2004

Ecologist Richard Levins argues population biologists must trade-off the generality, realism, and precision of their models since biological systems are complex and our limitations are severe. Steven Orzack and Elliott Sober argue that there are cases where these model properties cannot be varied independently of one another. If this is correct, then Levins's thesis that there is a necessary trade-off between generality, precision, and realism in mathematical models in biology is false. I argue that Orzack and Sober's arguments fail since Levins's thesis concerns the pragmatic features of model building not just the formal properties of models.
Data Models and the Acquisition and Manipulation of Data
Authors: Harris Todd
Published: February 2004

This paper offers an account of data manipulation in scientific experiments. It will be shown that in many cases raw, unprocessed data is not produced, but rather a form of processed data that will be referred to as a data model. The language of data models will be used to provide a framework within which to understand a recent debate about the status of data and data manipulation. It will be seen that a description in terms of data models allows one to understand cases in which data acquisition and data manipulation cannot be separated into two independent activities.
Reactive Oxygen Species Precede Protein Kinase C-δ Activation Independent of Adenosine Triphosphate–sensitive Mitochondrial Channel Opening in Sevoflurane-induced Cardioprotection
Authors: Bouwman R. Arthur , Musters René J. P. , van Beek-Harmsen Brechje J. , de Lange Jaap J. , Boer Christa
Published: February 2004

Background

In the current study, the authors investigated the distinct role and relative order of protein kinase C (PKC)-delta, adenosine triphosphate-sensitive mitochondrial K+ (mito K+(ATP)) channels, and reactive oxygen species (ROS) in the signal transduction of sevoflurane-induced cardioprotection and specifically addressed their mechanistic link.

Methods

Isolated rat trabeculae were preconditioned with 3.8% sevoflurane and subsequently subjected to an ischemic protocol by superfusion of trabeculae with hypoxic, glucose-free buffer (40 min) followed by 60 min of reperfusion. In addition, the acute affect of sevoflurane on PKC-delta and PKC-epsilon translocation and nitrotyrosine formation was established with use of immunofluorescent analysis. The inhibitors chelerythrine (6 microM), rottlerin (1 microM), 5-hydroxydecanoic acid sodium (100 microM), and n-(2-mercaptopropionyl)-glycine (300 microM) were used to study the particular role of PKC, PKC-delta, mito K+(ATP), and ROS in sevoflurane-related intracellular signaling.

Results

Preconditioning of trabeculae with sevoflurane preserved contractile function after ischemia. This contractile preservation was dependent on PKC-delta activation, mito K+(ATP) channel opening, and ROS production. In addition, on acute stimulation by sevoflurane, PKC-delta but not PKC-epsilon translocated to the sarcolemmal membrane. This translocation was inhibited by PKC inhibitors and ROS scavenging but not by inhibition of mito K+(ATP) channels. Furthermore, sevoflurane directly induced nitrosylation of sarcolemmal proteins, suggesting the formation of peroxynitrite.

Conclusions

In sevoflurane-induced cardioprotection, ROS release but not mito K+(ATP) channel opening precedes PKC-delta activation. Sevoflurane induces sarcolemmal nitrotyrosine formation, which might be involved in the recruitment of PKC-delta to the cell membrane.
Nuclear Factor κB and Anesthetic Preconditioning during Myocardial Ischemia-Reperfusion
Authors: Zhong Caiyun , Zhou Yamei , Liu Hong
Published: February 2004

Background

Volatile anesthetic preconditioning (APC) protects against myocardial ischemia-reperfusion (IR) injury, but the precise mechanisms underlying this phenomenon remain undefined. To investigate the molecular mechanism of APC in myocardial protection, the activation of nuclear factor (NF) kappaB and its regulated inflammatory mediators expression were examined in the current study.

Methods

Hearts from male rats were isolated, Langendorff perfused, and randomly assigned to one of three groups: (1) the control group: hearts were continuously perfused for 130 min; (2) the IR group: 30 min of equilibration, 15 min of baseline, 25 min of ischemia, 60 min of reperfusion; and (3) the APC + IR group: 30 min of equilibration, 10 min of sevoflurane exposure and a 5-min washout, 25 min of global ischemia, 60 min of reperfusion. Tissue samples were acquired at the end of reperfusion. NF-kappaB activity was determined by electrophoretic mobility shift assay. The NF-kappaB inhibitor, IkappaB-alpha, was determined by Western blot analysis. Myocardial inflammatory mediators, including tumor necrosis factor alpha, interleukin 1, intercellular adhesion molecule 1, and inducible nitric oxide synthase, were also assessed by Western blot analysis.

Results

Nuclear factor kappaB-DNA binding activity was significantly increased at the end of reperfusion in rat myocardium, and cytosolic IkappaB-alpha was decreased. Supershift assay revealed the involvement of NF-kappaB p65 and p50 subunits. APC with sevoflurane attenuated NF-kappaB activation and reduced the expression of tumor necrosis factor alpha, interleukin 1, intercellular adhesion molecule 1, and inducible nitric oxide synthase. APC also reduced infarct size and creatine kinase release and improved myocardial left ventricular developed pressure during IR.

Conclusions

The results of this study indicate that attenuation of NF-kappaB activation and subsequent down-regulation of NF-kappaB-dependent inflammatory gene expression plays an important role in the protective mechanism of APC against acute myocardial IR injury.
Morphine Preconditions Purkinje Cells against Cell Death under In Vitro Simulated Ischemia–Reperfusion Conditions
Authors: Lim Young Jin , Zheng Shuqiu , Zuo Zhiyi
Published: February 2004

Background

Morphine pretreatment via activation of delta1-opioid receptors induces cardioprotection. In this study, the authors determined whether morphine preconditioning induces ischemic tolerance in neurons.

Methods

Cerebellar brain slices from adult Sprague-Dawley rats were incubated with morphine at 0.1-10 microM in the presence or absence of various antagonists for 30 min. They were then kept in morphine- and antagonist-free buffer for 30 min before they were subjected to simulated ischemia (oxygen-glucose deprivation) for 20 min. After being recovered in oxygenated artificial cerebrospinal fluid for 5 h, they were fixed for morphologic examination to determine the percentage of undamaged Purkinje cells.

Results

The survival rate of Purkinje cells was significantly higher in slices preconditioned with morphine (> or = 0.3 microM) before the oxygen-glucose deprivation (57 +/- 4% at 0.3 microM morphine) than that of the oxygen-glucose deprivation alone (39 +/- 3%, P < 0.05). This morphine preconditioning-induced neuroprotection was abolished by naloxone, a non-type-selective opioid receptor antagonist, by naltrindole, a selective delta-opioid receptor antagonist, or by 7-benzylidenenaltrexone, a selective delta1-opioid receptor antagonist. However, the effects were not blocked by the mu-, kappa-, or delta2-opioid receptor antagonists, beta-funaltrexamine, nor-binaltorphimine, or naltriben, respectively. Morphine preconditioning-induced neuroprotection was partially blocked by the selective mitochondrial adenosine triphosphate-sensitive potassium channel antagonist, 5-hydroxydecanoate, or the mitochondrial electron transport inhibitor, myxothiazol. None of the inhibitors used in this study alone affected the simulated ischemia-induced neuronal death.

Conclusions

These data suggest that morphine preconditioning is neuroprotective. This neuroprotection may be delta1-opioid receptor dependent and may involve mitochondrial adenosine triphosphate-sensitive potassium channel activation and free radical production. Because morphine is a commonly used analgesic, morphine preconditioning may be explored further for potential clinical use to reduce ischemic brain injury.
Dual Exposure to Sevoflurane Improves Anesthetic Preconditioning in Intact Hearts
Authors: Riess Matthias L. , Kevin Leo G. , Camara Amadou K. S. , Heisner James S. , Stowe David F.
Published: February 2004

Background

Anesthetic preconditioning (APC) with sevoflurane reduces myocardial ischemia-reperfusion injury. The authors tested whether two brief exposures to sevoflurane would lead to a better preconditioning state than would a single longer exposure and whether dual exposure to a lower (L) concentration of sevoflurane would achieve an outcome similar to that associated with a single exposure to a higher (H) concentration.

Methods

Langendorff-prepared guinea pig hearts were exposed to 0.4 mM sevoflurane once for 15 min (H1-15; n = 8) or 0.4 mM (H2-5; n = 8) or 0.2 mM sevoflurane (L2-5; n = 8) twice for 5 min, with a 5-min washout period interspersed. Sevoflurane was then washed out for 20 min before 30 min of global no-flow ischemia and 120 min of reperfusion. Control hearts (n = 8) were not subjected to APC. Left ventricular pressure was measured isovolumetrically. Ventricular infarct size was determined by tetrazolium staining and cumulative planimetry. Values are expressed as mean +/- SD.

Results

The authors found a better functional return and a lesser percentage of infarction on reperfusion in H2-5 (28 +/- 9%) than in H1-15 (36 +/- 8%; P < 0.05), L2-5 (43 +/- 6%; P < 0.05), or control hearts (52 +/- 7%; P < 0.05).

Conclusion

These results suggest that APC depends not only on the concentration but also on the protocol used for preconditioning. Similarly to ischemic preconditioning, repeated application of the volatile anesthetic seems to be more important than the duration of exposure in initiating the signaling sequence that elicits APC at clinically relevant concentrations. Therefore, repeated cycles of anesthetic exposure followed by volatile anesthetic-free periods may be beneficial for APC in the clinical setting.
Mandibular Advancement Improves the Laryngeal View during Direct Laryngoscopy Performed by Inexperienced Physicians
Authors: Tamura Miki , Ishikawa Teruhiko , Kato Rie , Isono Shiroh , Nishino Takashi
Published: February 2004

Background

When oral or nasal fiberoptic laryngoscopy is attempted, mandibular advancement has been reported to improve the laryngeal view. The authors hypothesized that mandibular advancement may also improve the laryngeal view during direct laryngoscopy.

Methods

Forty patients undergoing elective surgery under general anesthesia were included in this study. After establishment of an adequate level of anesthesia and muscle relaxation, direct laryngoscopy was performed by inexperienced physicians. Four different maneuvers--simple direct laryngoscopy without any assistance (C), simple direct laryngoscopy with mandibular advancement (M), simple direct laryngoscopy with the BURP maneuver (backward, upward, rightward pressure maneuver of the larynx; B), and simple direct laryngoscopy with both mandibular advancement and the BURP maneuver (BM)--were attempted in each subject, and the laryngeal aperture was videotaped with each procedure. An instructor in anesthesiology who was blinded to the procedure evaluated the visualization by reviewing videotape off-line, using the Cormack-Lehane classification system (grades I-IV) and a rating score within each subject (1 = best view; 4 = poorest view). The Friedman test followed by the Student-Newman-Keuls test was performed for statistical comparison. P < 0.05 was considered significant.

Results

The laryngeal view was improved with M and B when compared with C (P < 0.05 by both rating and Cormack-Lehane evaluation). BM was the most effective method to visualize the laryngeal aperture (P < 0.05, vs. B and M by rating evaluation), whereas B and M were the second and the third most effective methods, respectively. No statistical difference was observed between B and M with the Cormack-Lehane classification.

Conclusion

Mandibular advancement improves the laryngeal view during direct laryngoscopy performed by inexperienced physicians.
ED50and ED95of Intrathecal Hyperbaric Bupivacaine Coadministered with Opioids for Cesarean Delivery
Authors: Ginosar Yehuda , Mirikatani Edward , Drover David R. , Cohen Sheila E. , Riley Edward T.
Published: February 2004

Background

Successful cesarean delivery anesthesia has been reported with use of small doses (5-9 mg) of intrathecal bupivacaine coadministered with opioids. This double-blind, randomized, dose-ranging study determined the ED50 and ED95 of intrathecal bupivacaine (with adjuvant opioids) for cesarean delivery anesthesia.

Methods

Forty-two parturients undergoing elective cesarean delivery with use of combined spinal-epidural anesthesia received intrathecal hyperbaric bupivacaine in doses of 6, 7, 8, 9, 10, 11, or 12 mg in equal volumes with an added 10 microg intrathecal fentanyl and 200 microg intrathecal morphine. Sensory levels (pinprick) were evaluated every 2 min until a T6 level was achieved. The dose was a success(induction) if a bilateral T6 block occurred in 10 min; otherwise, it was a failure(induction). In addition to being a success(induction), the dose was a success(operation) if no intraoperative epidural supplement was required; otherwise, it was a failure(operation). ED50 and ED95 for both success(induction) and success(operation) were determined with use of a logistic regression model.

Results

ED50 for success(induction) and success(operation) were 6.7 and 7.6 mg, respectively, whereas the ED95 for success(induction) and success(operation) were 11.0 and 11.2 mg. Speed of onset correlated inversely with dose. Although no clear advantage for low doses could be demonstrated (hypotension, nausea, vomiting, pruritus, or maternal satisfaction), this study was underpowered to detect significance in these variables.

Conclusions

The ED95 of intrathecal bupivacaine under the conditions of this study is considerably in excess of the low doses proposed for cesarean delivery in some recent publications. When doses of intrathecal bupivacaine less than the ED95, particularly near the ED50, are used, the doses should be administered as part of a catheter-based technique.
Thoracic and Lumbar Epidural Analgesia via the Caudal Approach Using Electrical Stimulation Guidance in Pediatric Patients
Authors: Tsui Ban C. H. , Wagner Alese , Cave Dominic , Kearney Ramona
Published: February 2004

Background

Nerve stimulation guidance (Tsui test) has been reported to be an effective alternative to radiographic imaging for proper catheter placement. The purpose of this study was to examine the success rate and complications of continuous caudal epidural analgesia since the implementation of routine use of the Tsui test at the authors' institution.

Methods

The authors examined prospectively collected data in their pediatric pain service database from 289 children who had attempted caudal placement of a lumbar or thoracic catheter between 1999 and 2002.

Results

In five patients (aged 5 months-1.6 yr), the catheter did not thread to the desired level and was abandoned in the operating room (technical success rate, 98.2%). Of the remaining 284 patients, the overall analgesic success rate of all caudal route epidural analgesia procedures was 84.9%. There was no significant difference in adequate pain control (success) in infants (aged 1 day-1 yr) versus older children (aged younger than 1 yr). The most common adverse effects were pruritus (26.1%) and nausea and vomiting (16.9%). Of the patients in our study, 57.7% had urinary catheters in situ; of those who did not have a catheter placed, 20.8% experienced urinary retention. The incidence of respiratory depression was 4.2%, but the administration of naloxone for severe respiratory depression was never necessary. Three percent of catheters were removed because of suspected contamination, but no epidural abscesses or systemic infection were noted.

Conclusions

The results of this study suggest that epidural catheter placement via the caudal approach using the Tsui test is an effective and reasonable alternative to direct lumbar and thoracic epidural analgesia in pediatric patients.
Original Investigations of Nerve Block Pain Management after Anterior Cruciate Ligament Reconstruction
Authors: Williams Brian A. , Kentor Michael L. , Vogt Molly T. , Vogt William B. , Coley Kim C. , Williams John P. , Roberts Mark S. , Chelly Jacques E. , Harner Christopher D. , Fu Freddie H.
Published: February 2004

Background

Anterior cruciate ligament reconstruction is a complex outpatient surgical procedure often associated with pain. Traditionally, the procedure is performed under general anesthesia and often requires the use of the PACU. Refractory pain and/or nausea/vomiting occasionally leads to an unplanned hospital admission. In this study, the authors examine the associations of nerve block analgesia for these patients and its associated reductions in PACU use, hospital admission, and hospital costs.

Methods

This was an observational, nonrandomized study in which existing data regarding patients' day-of-surgery outcomes were merged with hospital cost data. We reviewed a consecutive sample of 948 men and women who were in good health and underwent anterior cruciate ligament reconstruction in an outpatient surgery unit between July 1995 and June 1999.

Results

The use of nerve block analgesia was associated with reduced PACU admissions to 18% and decreased unplanned hospital admission rates from 17% to 4%. Multivariate linear regression analysis showed that patients bypassing the PACU had an associated hospital cost reduction of 12% (P = 0.0001), whereas patients who needed hospital admission had an associated hospital cost increase of 11% (P = 0.0003).

Conclusions

The use of nerve blocks for acute pain management in patients undergoing anterior cruciate ligament reconstruction is associated with PACU bypass and reliable same-day discharge. Although the cost savings for this one procedure are unlikely to generate sufficient cost savings via staffing reductions, extrapolating these results to a large volume of all types of invasive outpatient orthopedic procedures may have the potential to create significant hospital cost savings.
Histological organization and its relationship to function in the femur of Alligator mississippiensis
Authors: Lee Andrew H.
Published: February 2004

Histological analysis of a growth series of alligator femora tests the correlation between strain milieu and microstructure. From mid‐diaphyseal cross‐sections of these femora (n = 7), vascular canal orientation and density as well as collagen fibre organization were recorded. Throughout ontogeny, the proportion of transverse–spiral (TS) collagen in the dorsal cortex is significantly greater than it is in the ventral cortex (P = 0.008). This regional difference in the proportion of TS collagen is correlated with a regional difference in the state of peak principal strain (compressive or tensile). Nevertheless, the predominant orientation of collagen fibres is longitudinal, which is inconsistent with biomechanical hypotheses that involve peak principal or shear strains. Although the density and orientation of vascular canals do not show significant regional differences (P = 0.26 and P = 0.26, respectively), as with collagen orientation, the vascular canal orientation is predominantly longitudinal. The longitudinal organization of both the vascular canals and the collagen fibres is probably a consequence of longitudinal shifting of subperiosteal osteoid during femoral lengthening. When taken together, these data suggest that growth dynamics is the dominant influence on the histological organization of primary bony tissues in alligator femora.
Moral Objectivity and Reasonable Agreement: Can Realism Be Reconciled with Kantian Constructivism?
Authors: Lafont Cristina
Published: February 2004

Abstract.In this paper I analyze the tension between realism and antirealism at the basis of Kantian constructivism. This tension generates a conflictive account of the source of the validity of social norms. On the one hand, the claim to moral objectivity characteristic of Kantian moral theories makes the validity of norms depend on realist assumptions concerning the existence of shared fundamental interests among all rational human beings. I illustrate this claim through a comparison of the approaches of Rawls, Habermas and Scanlon. On the other hand, however, objections to moral realism motivate many Kantian constructivists to endorse the antirealist claim that reasonable agreement is the source of the validity of social norms. After analyzing the difficulties in the latter strategy, I try to show how a balance between the realist and antirealist elements of Kantian constructivism can be reached by drawing a sharper distinction between the justice and the legitimacy of social norms.
Depoliticizing Democracy
Authors: Pettit Philip
Published: February 2004

Abstract.It is now widely accepted as an ideal that democracy should be as deliberative as possible. Democracy should not involve a tussle between different interest groups or lobbies in which the numbers matter more than the arguments. And it should not be a system in which the only arguments that matter are those that voters conduct in an attempt to determine where their private or sectional advantage lies. Democracy, it is said, should promote public deliberation among citizens and authorities as to what does best for the society as a whole and should elicit decision‐making on that basis. But the ideal of deliberative democracy has two components—the deliberative and the democratic—and often they pull apart. In this paper I look in the first section at a series of problems that arise on the deliberative front, arguing that their resolution requires various degrees of depoliticization. And then I ask in the second whether the depoliticizing responses that those problems require are antithetical to the ideal of democracy. I argue that they are not in tension with the ideal, if that ideal is cast in the relatively revisionary, two‐dimensional form that I favour.1
Fused Modality or Confused Modality?
Authors: Dahlman Christian
Published: February 2004

Abstract. According to Svein Eng there are propositions concerning the law which are descriptive as well as normative, but cannot be separated into one descriptive and one normative proposition. Eng calls these propositions “fused” (“sammensmeltede”). In Eng's theory a proposition with “fused modality” is partly descriptive and partly normative, but cannot be classified as a separable combination of a claim about what the law “is” and a claim about what the law “ought to be.” In a “fused” proposition modality is a question of “degree.” The purpose of this article is to show why Eng's theory should be rejected. The introduction of “fused modality” adds nothing of value to legal theory. Eng claims to have discovered a class of propositions not previously accounted for, but this is not the case. The lawyer Eng talks about as making a “fused” proposition is simply a lawyer logically confused.
Law and Coherence
Authors: Hage Jaap
Published: February 2004

Abstract. This paper deals with the questions of whether the law should be coherent and what this coherence would amount to. In this connection so‐called “integrated coherentism” is introduced. According to integrated coherentism, an acceptance set is coherent if and only if it contains everything that should rationally be accepted according to what else one accepts and does not contain anything that should rationally be rejected according to what else one accepts. Such an acceptance set is ideally a theory of everything, including amongst others standards for rational aceptance. On the assumption that the law, as a social phenomenon, is what the best theory about the law says it is, the law must be coherent, because the best theory of the law is part of an integratedly coherent theory of everything. This view is compatible with Raz's view that the law stems from different sources that need not be coherent in the sense that they consistently elaborate the same underlying principles or policies. Raz's view is not a consequence of integrated coherentism, however.