bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relative Effect of Cue Interaction
Authors: Tangen Jason M. , Allan Lorraine G.
Published: August 2003

It is well established that two predictor cues ( A and B) of a common outcome interact in that the judgement of the relationship between each cue and the outcome is influenced by the pairing history of the other cue with that outcome. For example, when the contingency of A with an outcome is weaker than the contingency of B with that outcome, the rating of the predictiveness of A is reduced relative to a situation where only A is paired with the outcome. One explanation of such cue interaction effects is provided by the conditional Δ P account. Spellman (1996b) derived a counterintuitive prediction of the conditional Δ P account where cue interaction should not occur under certain conditions even though a relatively poor predictor of an outcome is paired with a relatively good predictor of that outcome. However, Spellman (1996b) did not provide data to evaluate this prediction. In the present paper, we report the relevant data and show that they are consistent with the conditional Δ P account. A competing account of cue interaction is provided by the Rescorla-Wagner (RW) model. We derive the predictions of the RW model for the conditions specified by Spellman (1996b), and show that at asymptote the predictions of the RW model are identical to those of the conditional Δ P account.
An Associative Model of Rat Serial Pattern Learning in Three-Element Sequences
Authors: Wallace Douglas G. , Fountain Stephen B.
Published: August 2003

Hypotheses ranging from subsymbolic to symbolic have been proposed to account for rat sequential behaviour, and in the subsymbolic domain alone there are multiple proposed subsymbolic processes or factors thought to affect serial behaviour. A behavioural study and computer simulations were conducted to evaluate these hypotheses, and a new computational associative model based on pairwise associations and generalization was evaluated. Seven 3-element sequences were selected for study that systematically (1) varied sequence discriminability, (2) varied reward magnitude, and (3) manipulated the order of food quantities. Neither element discriminability nor response enhancement subsymbolic processes in isolation were able to account for the behavioural data; however, simulations from the computational model known as the sequential pairwise associative memory (SPAM) model with a log-linear mapping of stimulus dimension items to food quantities correlated well with the behavioural data. SPAM accounts for differential element anticipation in different sequences by appealing to pairwise association of sequence events and generalization between cues as the principal factors mediating pattern tracking in three-element sequences.
Electronically Tunable Quadrature Oscillator Using Translinear Conveyors and Grounded Capacitors
Authors: Maheshwari Sudhanshu
Published: August 2003

A new electronically tunable current‐mode sinusoidal oscillator with three quadrature outputs is presented. The proposed circuit employs three translinear conveyors and two grounded capacitors to realize three quadrature outputs with independent frequency control. The circuit requires no resistors and the frequency of the oscillator can be varied over a wide range by external current control. RSPICE simulation results using the bipolar
implementation of translinear conveyors are given to support the proposed circuit.
Simulation of a Novel Bipolar‐FET Type‐S, Negative Resistance Circuit
Authors: Kumar Umesh
Published: August 2003

A new circuit which uses FET and bipolar transistor is given. It exhibits Type‐S differential negative resistance and a theoretical explanation is appended along with PSPICE simulation.
Simulation and Realization of Some CMOS‐Transconductor Vhf Filters
Authors: Kumar Umesh
Published: August 2003

CMOS circuits for integrated analog filters at very high frequencies have been designed through PSPICE based on the Transconductance‐C integrator. They have been implemented on the bread board and many filters i.e. LP, BP, Elliptic LP etc. are simulated and realized.
Organization of a Circuit Simulator Based on Waveform‐Relaxation Method
Authors: Kumar Umesh
Published: August 2003

The design of a circuit simulator based on the WR procedure is described. The relevant algorithms are presented.
Slight respiratory irritation but not inflammation in mice exposed to (1→3)‐β‐D‐glucan aerosols
Authors: Korpi A. , Kasanen J.-p. , Kosma V.-m. , Rylander R. , Pasanen A.-l.
Published: August 2003

Airway irritation effects after single and repeated inhalation exposures to aerosols of β‐glucan (grifolan) were investigated in mice. In addition, the effects on serum total immunoglobulin E (IgE) production and histopathological inflammation in the respiratory tract were studied. The β‐glucan aerosols provoked slight sensory irritation in the airways, but the response was not concentration dependent at the levels studied. Slight pulmonary irritation was observed after repeated exposures. No effect was found on the serum total IgE levels, and no signs of inflammation were seen in the airways 6 h after the final exposure. The results suggest that, irrespective of previous fungal sensitization of the animals, inhaled β‐glucan may cause symptoms of respiratory tract irritation but without apparent inflammation. Respiratory tract irritation reported after inhalation of fungi may not be entirely attributed to β‐glucan.
Poloxamer 407‐induced atherosclerosis in mice appears to be due to lipid derangements and not due to its direct effects on endothelial cells and macrophages
Authors: Johnston Thomas P. , Li Yuai , Jamal Ahmed S. , Stechschulte Daniel J. , Dileepan Kottarappat N.
Published: August 2003

Coronary heart disease secondary to atherosclerosis is still the leading cause of death in the US. Animal models used for elucidating the pathogenesis of this disease primarily involve rabbits and pigs. Previous studies from this laboratory have demonstrated intraperitoneal injections of poloxamer 407 (P‐407) in both male and female mice will lead to hyperlipidemia and atherosclerosis, suggesting the use of this polymer to develop a mouse model of atherosclerosis. In order to understand the mechanism of P‐407‐induced hyperlipidemia and vascular lesion formation, we evaluated the direct effects of P‐407 on endothelial cell and macrophage functions in vitro, and its in vivo effects on the oxidation of circulating lipids following long‐term (4 month) administration. Our results demonstrated that incubation of P‐407 with human umbilical vein endothelial cells in culture did not influence either cell proliferation or interleukin‐6 and interleukin‐8 production over a concentration range of 0‐40 μM. In addition, nitric oxide production by macrophages was not affected by P‐407 over a concentration range of 0‐20 μM. Finally, we demonstrated that while P‐407 could not induce the oxidation of LDL‐C in vitro, long‐term (4 month) administration of P‐407 in mice resulted in elevated levels of oxidized lipids in the plasma. Thus, it is suggested that the formation of atherosclerotic lesions in this mouse model of atherosclerosis does not result from either direct stimulation of endothelial cells or macrophage activation by P‐407. Instead, these data would support the premise that oxidation of lipids (perhaps low‐density lipoprotein cholesterol) by an indirect mechanism following injection of P‐407 may represent one of the mechanisms responsible for atheroma formation.
Characterization of the growth‐inhibitory and apoptosis‐inducing activities of a triterpene saponin, securioside B against BAC1.2F5 macrophages
Authors: Yui Satoru , Kudo Tomoya , Hodono Kazumi , Mimaki Yoshihiro , Kuroda Minpei , Sashida Yutaka , Yamazaki Masatoshi
Published: August 2003

Background: Since the growth state of macrophages in local pathological sites is considered a factor that regulates the processes of many disease, such as tumors, inflammation, and atherosclerosis, the substances that regulate macrophage growth or survival may be useful for disease control. We previously reported that securiosides A and B, novel triterpene saponins, exerted macrophage‐oriented cytotoxicity in the presence of a L‐cell‐conditioned medium containing macrophage colony‐stimulating factor (M‐CSF), while the compounds did not exhibit an effect on macrophages in the absence of the growth‐stimulating factors.

Aim: This study was undertaken to characterize the growth‐inhibitory and the apoptosis‐inducing activities of securioside B, focusing on the effects of the macrophage‐growth factor(s), and to examine the implication of a mitochondria pathway in apoptosis induction.

Methods: The effect of securioside B on a murine macrophage cell line (BAC1.2F5) was examined by MTT assay and lactose dehydrogenase release assay in the presence of L‐cell‐conditioned medium, M‐CSF, or granulocyte‐macrophage CSF (GM‐CSF).

Results: Securioside B inhibited the growth of the cells stimulated by recombinant M‐CSF or GM‐CSF, but it scarcely induced cytolysis of the cells under the same conditions. Moreover, securioside B did not induce cell death when the compound only was added to the cells. On the other hand, the compound extensively induced apoptotic cell death in the presence of L‐cell‐conditioned medium, suggesting that apoptosis induction by securioside B requires the additional factor(s) present in L‐cell‐conditioned medium. Securioside B plus L‐cell‐conditioned medium induced the activation of caspase‐3 and caspase‐9, but not caspase‐8. In addition, cytochrome c release from the mitochondria into the cytosol, and disrupted mitochondria membrane potential, was also observed in the apoptotic BAC1.2F5 cells.

Conclusion: These data suggest that securioside B has growth‐inhibitory activity against growth factor‐stimulated macrophages, and that it induces apoptotic macrophage death through the activation of a mitochondrial pathway in the presence of L‐cell‐conditioned medium.
Circulating proangiogenic cytokines and angiogenesis inhibitor endostatin in untreated patients with chronic lymphocytic leukemia
Authors: Gora-Tybor Joanna , Blonski Jerzy Z. , Robak Tadeusz
Published: August 2003

The serum concentration of two pro‐angiogenic cytokines: basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF‐β1), and anti‐angiogenic factor endostatin in the serum of 80 never treated B‐cell chronic lymphocytic leukemia (CLL) patients and 27 healthy volunteers was measured using an enzyme linked immunosorbent assay. The serum levels of both bFGF and TGF‐β1 were found to be significantly higher in the CLL group (median 40.5 pg/ml and 38.6 ng/ml respectively) when compared to the control group (median 9.4 pg/ml and 18.9 ng/ml, respectively) (P < 0.001). The levels of endostatin were not significantly different in CLL and control groups (median 12.3 ng/ml and 8.4 ng/ml, respectively) (P = 0.09). In the group of CLL patients the level of bFGF was significantly higher in patients with progressive disease as compared with patients with stable disease (median 90.5 pg/ml and 40.5 pg/ml respectively) (P < 0.001). Patients in Rai stage III and IV also had significantly higher levels of bFGF than patients in Rai stage 0‐II (median 100.1 pg/ml and 29.3 pg/ml respectively) (P < 0.001). The levels of both TGF‐β1 and endostatin were lower in patients in Rai stage III and IV (median 28.9 ng/ml and 9.1 ng/ml respectively) than in patients in Rai stage 0‐II (42.8 ng/ml and 13.1 ng/ml respectively) (P < 0.001 and P = 0.002 respectively). The level of endostatin was also lower in the group of CLL patients with progressive disease (median 10.0 ng/ml) as compared to patients with stable disease (median 20.5 ng/ml) (P = 0.008). In conclusion, the disturbance in the balance between pro‐ and anti‐angiogenic factors may have an important influence on the course of CLL.
mRNA expression and release of interleukin‐8 induced by serum amyloid A in neutrophils and monocytes
Authors: Ribeiro Fernanda Pereira , Furlaneto Cristiane Jaciara , Hatanaka Elaine , Ribeiro Wesley Bueno , Souza Glaucia Mendes , Cassatella Marco A. , Campa Ana
Published: August 2003

The acute phase response is a systemic reaction to inflammatory processes characterized by multiple physiological adaptations, including the hepatic synthesis of acute‐phase proteins. In humans, serum amyloid A (SAA) is one of the most prominent of these proteins. Despite the huge increase of serum levels of SAA in inflammation, its biological role remains to be elucidated, even though SAA is undoubtedly active in neutrophils. In a previous study, we reported that SAA induces the release of tumor necrosis factor‐α, interleukin (IL)‐1β and IL‐8 from human blood neutrophils. Here, we extend our earlier study, focusing on the effect of SAA on neutrophil IL‐8 transcription and on the signaling pathways involved. We demonstrate herein that SAA, in relatively low concentrations (0.4‐100 μg/ml) compared with those found in plasma in inflammatory conditions, induces a dose‐dependent release of IL‐8 from neutrophils. The p38 mitogen‐activated protein kinase inhibitor SB 203580 inhibits the IL‐8 mRNA expression and the release of protein from neutrophils. The release of IL‐8 from SAA‐stimulated neutrophils is strongly suppressed by the addition of N‐acetyl‐l‐cysteine, α‐mercaptoethanol, glutathione, and dexamethasone. SAA also induces IL‐8 expression and release from monocytes. In conclusion, SAA appears to be an important mediator of the inflammatory process, possibly contributing to the pool of IL‐8 produced in chronic diseases, which may play a role in degenerative diseases.
Role of interleukin‐15 and interleukin‐18 in the secretion of sIL‐6R and sgp130 by human neutrophils
Authors: Jablonska E. , Marcinczyk M.
Published: August 2003

Background: Available data indicate that neutrophils (PMN) produce a wide range of cytokines with the potential to modulate immune response. Recent investigation have shown that interleukin (IL)‐15 and IL‐18 potentiated several functions of normal neutrophils. It has been reported that IL‐18‐induced cytokine production may be significantly enhanced by coincident addition of IL‐15.

Aims: In the present study we compared the effect of recombinant human (rh)IL‐15 and rhIL‐18 as well as effect of a rhIL‐15 and rhIL‐18 combination on the induction secretion of sIL‐6Rα and sgp130 by human neutrophils. Methods: PMN were isolated from heparinized whole blood of healthy persons. The PMN were cultured for 18 h at 37°C in a humidified incubator with 5% CO2. rhIL‐15 and/or rhIL‐18 and lipopolysaccharide were tested to PMN stimulation. The culture supernatants of PMN were removed and examined for the presence of sIL‐6R and sgp130 by human enzyme‐linked immunosorbent assay kits. Cytoplasmic protein fractions of PMN were analysed for the presence of sIL‐6R and sgp130 by western blotting using monoclonal antibodies capable of detecting these proteins. Cells were lysed and cytoplasmic proteins were electrophoresed on sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. The resolved proteins were transferred onto nitrocellulose and incubated with the primary monoclonal antibodies anti‐sIL‐6R and anti‐sgp130. The membranes were incubated at room temperature with alkaline phosphatase anti‐mouse immunoglobulin G. Immunoreactive protein bans were visualized by an AP Conjugate Substrate Kit.

Results and conclusion:The results of our investigation revealed that IL‐15 alone, similarly to IL‐18, has no significant ability for the regulation of both soluble IL‐6 receptors, sIL‐6R and sgp130, released by human neutrophils. It is interesting to note that the secretion of sgp130 was changed after PMN stimulation with rhIL‐15 in the presence of rhIL‐18. The combination of rhIL‐15 and rhIL‐18 was shown to induce PMN to secretion relatively higher amounts of sgp130 compared with the stimulation of PMN with rhIL‐15 alone and rhIL‐18 alone. The results obtained suggest that IL‐15 and IL‐18, belonging to the inflammatory cytokines, through the regulation of sgp130 secretion must be also considered as anti‐inflammatory mediators that may influence the balance reactions mediated by the IL‐6 cytokine family.
Cytokine soluble receptors in perinatal and early neonatal life
Authors: Protonotariou Efthimia , Rizos Demetrios , Malamitsi-puchner Ariadne , Moira Evangelia , Sarandakou Angeliki , Salamalekis Emmanuil
Published: August 2003

Background: In contrast to cellular receptors, soluble receptors do not enhance the cellular activation because they do not have transmembranic and cytoplasmic parts, acting thereby as endogenous regulatory mechanisms against systemic functions of cytokines.

Aim: To measure serum concentrations of the soluble interleukin‐2 receptor (sIL2R), soluble interleukin‐4 receptor (sIL4R), soluble interleukin‐6 receptor (sIL6R), and soluble tumor necrosis factor‐α receptor I and soluble tumor necrosis factor‐α receptor II, during the perinatal and early neonatal period, in order to evaluate their role in activation of immune response in labor and the first days postpartum.

Methods: Soluble receptor serum concentrations were determined by enzyme‐linked immunosorbent assay, in 45 healthy, full‐termed neonates during the first and fifth days after birth, in 25 of their mothers (MS), in 25 samples of umbilical cords (UC) and in 25 healthy adult donors age‐matched with the mothers (controls).

Results: Soluble receptor serum concentrations showed considerable changes during labor and early neonatal life, being significantly higher both in MS (except sIL6R) and in neonatal sample UC, first and fifth days after birth, compared with controls (P < 0.0001). Neonatal serum sIL2R and sIL6R increased significantly from birth to the fifth day, while the remaining receptors showed a rapid increase in the first day (P < 0.0001), declining significantly thereafter (P < 0.0001).

Conclusion: Our findings suggest that the elevated concentrations of all studied soluble cytokine receptors reflect the activation of immune response, and represent also regulatory protective mechanisms for mother and fetus‐neonate against the systemic function of cytokines during labor and early neonatal life.
Mathematical Models of the Complete Course of HIV Infection and AIDS
Authors: Duffin R. Paul , Tullis Richard H.
Published: August 2003

Mathematical models of HIV infection are important to our understanding of AIDS. However, most models do not predict both the decrease in CD4+ T cells and the increase in viral load seen over the course of infection. By including terms for continuous loss of CD4+ T cells and incorporating alteration in viral clearance and viral production, two new models have been created that accurately predict the dynamics of the disease. The first model is a clearance rate reduction model and is based on a 10% per year decrease in both viral clearance and CD4+ T cell levels. A macrophage reservoir model incorporating the observation that macrophage viral production increases up to 1000 fold in the presence of opportunistic infections that become increasingly common as disease progresses. Both viral clearance and macrophage reservoir models predict the expected decrease in T cell levels and rise in viral load observed at the onset of AIDS.
A Cellular Automaton Model of Brain Tumor Treatment and Resistance
Authors: Schmitz Jonathan E. , Kansal Anuraag R. , Torquato Salvatore
Published: August 2003

We have extended an automaton model of brain tumor growth to study the effects of treatment. By varying three treatment parameters, we can simulate tumors that display clinically plausible survival times. Much of our work is dedicated to heterogeneous tumors with both treatment‐sensitive and treatment‐resistant cells. First, we investigate two‐strain systems in which resistant cells are initialized within predominantly sensitive tumors. We find that when resistant cells are not confined to a particular location, they compete more effectively with the sensitive population. Moreover, in this case, the fraction of resistant cells within the tumor is a less important indicator of patient prognosis when compared to the case in which the resistant cells are scattered throughout the tumor. In additional simulations, we investigate tumors that are initially monoclonal and treatment‐sensitive, but that undergo resistance‐mutations in response to treatment. Here, the tumors with both very frequent and very infrequent mutations develop with more spherical geometries. Tumors with intermediate mutational responses exhibit multi‐lobed geometries, as mutant strains develop at localized points on the tumors′ surfaces.
A Mathematical Model of Continuous HIV Mutations Eluding Immune Defence
Authors: Wilson D. P. , McElwain D. L. S.
Published: August 2003

We develop a description of HIV mutations based upon a continuum representation of the fitness of the virus, including the interaction of the virus with both specific Th1 lymphocytes as well as cross‐reactive cells. This deterministic model allows a straightforward measure of the diversity of viral population and reproduces the observed increase in diversity as the disease progresses in an untreated patient. We use the diversity threshold theory, extending the modelling to track mutations on a continuum. When the diversity threshold is exceeded, the host immune system collapses.
A Mathematical Model of an In Vitro Experiment to Investigate Endothelial Cell Migration
Authors: Plank M. J. , Sleeman B. D. , Jones P. F.
Published: August 2003

Angiogenesis, the growth of new blood vessels from existing ones, is an important, yet not fully understood, process and is involved in diseases such as rheumatoid arthritis, diabetic retinopathy and solid tumour growth. Central to the process of angiogenesis are endothelial cells (EC), which line all blood vessels, and are capable of forming new capillaries by migration, proliferation and lumen formation. We construct a cell‐based mathematical model of an experiment (Vernon, R.B. and Sage, E.H. (1999) “A novel, quantitative model for study of endothelial cell migration and sprout formation within three‐dimensional collagen matrices”, Microvasc. Res. 57, 118–133) carried out to assess the response of EC to various diffusible angiogenic factors, which is a crucial part of angiogenesis. The model for cell movement is based on the theory of reinforced random walks and includes both chemotaxis and chemokinesis. Three‐dimensional simulations are run and the results correlate well with the experimental data. The experiment cannot easily distinguish between chemotactic and chemokinetic effects of the angiogenic factors. We, therefore, also run two‐dimensional simulations of a hypothetical experiment, with a point source of angiogenic factor. This enables directed (gradient‐driven) EC migration to be investigated independently of undirected (diffusion‐driven) migration.
A Novel Mixed‐Mode Current‐Controlled Current‐Conveyor‐Based Filter
Authors: Abuelma′atti Muhammad Taher
Published: August 2003

A new mixed‐mode biquad circuit is presented. The circuit uses four dual‐output second‐generation currentcontrolled current‐conveyors (DOCCCIIs) and two grounded capacitors and can realize lowpass, highpass, bandpass and notch responses from the same topology. The circuit can be driven by voltage or current and its output can be voltage or current. The parameters ωo
and ωo
/Qo
enjoy independent electronic tunability. Simulation results are included.
Optimisation of Temperature Fields of Microsystems with Self‐Organising Neural Nets
Authors: Bratek P. , Kos A.
Published: August 2003

Thermal modelling and optimisation of parameter distributed systems is a rather time‐consuming process. In this paper the problem of optimisation of temperature fields of VLSI circuits and systems is attacked by a selforganising neural net. The net directly solves the task generated by a heuristic algorithm. No physical model of thermal phenomena is used. The proposed method is simple. Some examples and statistical results are presented.
The proposed method is addressed mostly to large, high‐speed system designs.
Preparation, Characterization and Electrochemical Lithium Insertion Into the New Organic–Inorganic Poly(3,4‐Ethylene Dioxythiophene)/V2O5Hybrid
Authors: Kwon Chai-Won , Murugan A. Vadivel , Campet Guy
Published: August 2003

Poly(3,4‐ethylene dioxythiophene) (PEDOT) has been inserted between the layers of crystalline V2O5
via the in situ
polymerization of EDOT within the framework of the oxyde. The insertion increases the bidimensionality of the
V2O5
host by the layer separation but results in a random layer stacking structure, leading to broadening of the energy state distribution. According to electrochemical measurements, the hybrids showed reversible specific capacities up to ∼330
mAh/g at 15mA/g between 2 and 4.4V vs. Li+
/Li.
Novel Grounded Capacitor All‐Pass and Notch Filters Using Current Conveyors and Differential Amplifier
Authors: Saraswat R. , Pal K. , Rana S.
Published: August 2003

Three circuits each realizing second‐order all‐pass/notch filter transfer functions are reported. All circuits use grounded capacitors and are suitable for IC implementation. These circuits offer the advantages of high input impedance and low output impedance and are superior to all earlier realisations.
John Neville Keynes's Solution to the English Methodenstreit
Authors: Moore Gregory
Published: August 2003

John Neville Keynes is best known for being the father of John Maynard Keynes and for writing The Scope and Method of Political Economy (1891). The lesser of these achievements was widely accepted as the definitive methodological tract in the field of political economy in the late-Victorian period. In this publication Keynes shed new light on many of the pressing methodological and epistemological problems of the day; he supplied the methodological underpinnings to Alfred Marshall's majestic synthesis of late-Victorian theoretical opinion, as articulated in his Principles of Economics (1890); and, whatis of paramount concern to me in this paper, he employed some deft rhetoric to hasten the end of the long and acrimonious methodological debate between the orthodox and historical economists that is now generally referred to as the English Methodenstreit or “battle of methods.” Keynes consciously strove to provide a solution to the “battle of methods” that would be acceptable to both the orthodox and historical economists and, for this reason, The Scope and Method is understandably characterized by a conciliatory tone and repeated, almost desperate, attempts to see value in arguments from both sides of the conceptual divide. Keynes nonetheless failed in his quest to be even-handed. He was a logician of the first order who was extremely impressed by the neat logical lines of the orthodox framework, and hence, for all his intellectual honesty and obvious good will, he could not help but interpret the debate through orthodox spectacles. The chief rhetorical ploy he drew upon to achieve this orthodox-leaning settlement between the principal antagonists was the unconscious one of the “passive-aggressive” in which the advocate repeatedly makes the outward motions of conceding ground while, in effect, conceding little. The specific mechanics of this strategy entailed reformulating each precept from the historicist conceptual framework so that it would not be in conflict with its nearest orthodox opposite (itself carefully reinterpreted by Keynes), either by showing that it was identical to this orthodox opposite or by arguing that different precepts were appropriate in different situations, and then dismissing the entire methodological debate—which was then in its third decade—as one long and lamentable misunderstanding. Keynes was ably assisted in executing this strategy by his Cambridge colleagues and, for this reason, the quest to settle the debate by providing orthodox interpretations of the precepts then at stake may be termed the “Cambridge solution.” Marshall and Henry Sidgwick played particularly important roles in carrying this rhetorical assault, as the former's more genuine sympathy for many of the historicist ideas and the latter's celebrated honesty made the Cambridge quest appear sincere.
On Central Banking “Rules”: Tooke's Critique of the Bank Charter Act of 1844
Authors: Smith Matthew
Published: August 2003

The main opponent to the Bank Charter Act of 1844 in the Currency-Banking School debates of the 1840s and 1850s was undoubtedly Thomas Tooke (1774–1858). As is well known, the 1844 Bank Act embodied the Currency School's plan for the institutional separation of the Bank's “public” function of issuing banknotes in exchange for coin (bullion) from its “private” business of banking, consisting of receiving deposits, buying and selling securities in the open market, and discounting bills brought to its door. The objective of this plan was to compel the Bank of England to issue its banknotes pari pasu with changes in its bullion reserves. The Bank Charter Act of 1844 was perhaps the first attempt to introduce central banking “rules.” Tooke's grounds for criticizing the Act are, therefore, of interest to contemporary monetary economists. From 1840 until his last publication in 1857, Tooke engaged in a relentless campaign against the institutional separation of Bank of England functions under the 1844 Act. Before the Act's inception Tooke criticized the Currency School's plan on theoretical, as well as policy grounds. After its inception Tooke mainly criticized the 1844 Bank Act for actually contributing to monetary instability. These criticisms stemmed from Tooke's long-established position on banking policy together with the Banking School theory he largely developed in the early 1840s.
Das Adam Smith Problem: Its Origins, the Stages of the Current Debate, and One Implication for Our Understanding of Sympathy
Authors: Montes Leonidas
Published: August 2003

Scholars have long been interested in the apparent dichotomy between sympathy and self-interest in Smith. The question of the consistency betweenThe Theory of Moral Sentiments(TMS) andAn Inquiry into the Nature and Causes of the Wealth of Nations(WN)—the famousDas Adam Smith Problem—is definitely still relevant for anyone attracted to Smith scholarship. Although there is some agreement that the two works are consistent and, furthermore, parts of an incomplete system, it seems that theProblemcontinues to attract interest, not only for its historical and philosophical appeal, but also perhaps for its implications for the current economics-and-ethics debate.
The Search for a Practical Approach to Emerging Diseases: The Case of Severe Acute Respiratory Syndrome (SARS)
Authors: Selmi Carlo , Ansari Aftab A. , Invernizzi Pietro , Podda Mauro , Gershwin M. Eric
Published: August 2003

The plague, which the Board of Health had feared might enter with
the German troops into the Milanese, had entered it indeed,
as is well known; and it is likewise well known, that it paused not
here, but invaded and ravaged a great part of Italy. (A. Manzoni,
The Bethrothed, 1826)
Phage Display Based Cloning of Proteins Interacting with the Cytoplasmic Tail of Membrane Immunoglobulins
Authors: Geisberger Roland , Prlic Martin , Achatz-Straussberger Gertrude , Oberndorfer Iris , Luger Elke , Lamers Marinus , Crameri Reto , Appenzeller Ulrich , Wienands Jürgen , Breitenbach Michael , Ferreira Fatima , Achatz Gernot
Published: August 2003

The reduced quantity and quality of serum immunoglobulins (sIgs) in mutant mice expressing truncated cytoplasmic tails of IgE and IgG1 indicate an active role for the cytoplasmic domains of mIgG1 and mIgE. We used phage display technology to identify candidate proteins able to interact with the cytoplasmic tail of mIgE. Using a murine cDNA B cell library displayed on the surface of phage as prey and the 28 amino acid long cytoplasmic tail of IgE as bait, we isolated phage encoding the murine hematopoietic progenitor kinase 1 (HPK1). Surface plasmon resonance analysis measurements confirmed affinity of HPK1 to the mIgE cytoplasmic tail and revealed association to other immunoglobulin isotypes as well. Immunoprecipitation experiments, using lysates from two B cell lines expressing nitrophenyl (NP) specific mIgE molecules showed co‐precipitation of IgE and HPK1. The interaction of HPK1 with the cytoplasmic domains of membrane immunoglobulins indicate an active role of the tails as part of an isotype specific signal transduction, independent from the Igα/Igβ heterodimers, and may represent a missing link to upstream regulatory elements of HPK1 activation.
Altered Affinity Maturation in Primary Response to (4‐hydroxy‐3‐nitrophenyl) Acetyl (NP) after Autologous Reconstitution of Irradiated C57BL/6 Mice
Authors: De Trez Carl , Van Acker Annette , Vansanten Georgette , Urbain Jacques , Brait Maryse
Published: August 2003

Immune responses developing in irradiated environment are profoundly altered. The memory anti‐arsonate response of A/J mice is dominated by a major clonotype encoded by a single gene segment combination called CRIA. In irradiated and autoreconstituted A/J mice, the level of anti‐ARS antibodies upon secondary immunization is normal but devoid of CRIA antibodies. The affinity maturation process and the somatic mutation frequency are reduced. Isotype switching and development of germinal centers (GC) are delayed.

The primary antibody response of C57BL/6 mice to the hapten (4‐hydroxy‐3‐nitrophenyl) acetyl
(NP)‐Keyhole Limpet Hemocyanin (KLH) is dominated by antibodies encoded by a family of closely
related VH genes associated with the expression of the λ1 light chain.We investigated the anti‐NP
primary response in irradiated and autoreconstituted C57BL/6 mice. We observed some splenic
alterations as previously described in the irradiated A/J model. Germinal center reaction is delayed
although the extrafollicular foci appearance is unchanged. Irradiated C57BL/6 mice are able to mount
a primary anti‐NP response dominated by λ1 positive antibodies but fail to produce high affinity
NP‐binding IgGl antibodies. Following a second antigenic challenge, irradiated mice develop enlarged
GC and foci. Furthermore, higher affinity NP‐binding IgG1 antibodies are detected.
Modulation of TNF‐α Secretion in Peripheral Blood Mononuclear Cells by Cocoa Flavanols and Procyanidins
Authors: Mao T. K. , van de Water J. , Keen C. L. , Schmitz H. H. , Gershwin M. E.
Published: August 2003

Epidemiological reports have suggested that the consumption of foods rich in flavonoids is associated with a lower incidence of certain degenerative diseases, including cardiovascular disease. Flavanols and their related oligomers, the procyanidins CFP, isolated from cocoa can modulate the production and level of several signaling molecules associated with immune function and inflammation in vitro, including several cytokines and eicosanoids. To further elucidate the potential immuno‐modulatory functions of flavanol‐rich cocoa, the present investigation examined whether isolated CFP fractions (monomers through decamers) influence the secretion of tumor necrosis factor‐α (TNF‐α) from resting and phytohemagluttinin (PHA)‐stimulated human peripheral blood mononuclear cells (PBMC). We used an in vitro culture system where PBMC from 14 healthy subjects were introduced to individual CFP fractions for 72 h prior to measuring the levels of TNF‐α released. The intermediate‐sized CFP fractions (tetramers through octamers) were the most active on resting cells, causing a 3–4 fold increase in TNF‐α relative to media baseline. The monomers and dimers were the least stimulatory of the fractions tested, displaying a 42 and 31% increase, respectively, over media control, whereas the trimers, nonamers and decamers showed an intermediate stimulation of this cytokine. In the presence of PHA, the intermediate‐sized CFP fractions again were the most active, enhancing TNF‐α secretion in the range of 48–128% relative to the PHA control. The monomers and dimers were slightly inhibitory (–1.5 and –15%, respectively), while trimers, nonamers and decamers stimulated moderate increases in TNF‐α levels (13, 19 and 15%, respectively). The above results lend support to the concept that CFP can be immunomodulatory. The stimulation of TNF‐α secretion may contribute to the putative beneficial effects of dietary flavanoids against microbial infection and tumorigenesis.
Kupffer Cell‐mediated Recruitment of Dendritic Cells to the Liver Crucial for a Host Defense
Authors: Matsuno Kenjiro , Nomiyama Hisayuki , Yoneyama Hiroyuki , Uwatoku Ryosuke
Published: August 2003

Tissue recruitment of dendritic cells (DCs) is essential for antigen presentation. When latex particulates were injected intravenously into rats, DC precursors were recruited to the liver. Propionibacterium acnes also induced the recruitment of definite mouse DC precursors. These DCs initially showed a selective binding to Kupffer cells. In the Kupffer cell‐depleted rats, DCs could neither be recruited to the liver nor adhere to sinusoidal walls. Pretreatment with varied monosaccharides in vitro showed that sugar residues consisting of N‐acetylgalactosamine were necessary for this binding. Mouse DC precursors had CC‐chemokine receptor 1 and 5, while granulama tissues and rat Kupffer cells expressed the corresponding chemokine, macrophage inflammatory protein‐1α. Recruited DC precursors phagocytosed latex or bacteria and some of them soon translocated to hepatic nodes and induced the immune response there. We conclude that after invasion of pathogens, Kupffer cells not only scavenge them but also recruit DCs/DC precursors via chemokine‐ and N‐acetylgalactosamine‐mediated interactions. The accelerated DC traffic and the presence of blood‐lymph translocation would induce rapid and efficient immune responses and thus contribute to the local defense to antigens within liver tissues as well as systemic defense to blood‐borne antigens.
FIZZ1 and Ym as Tools to Discriminate between Differentially Activated Macrophages
Authors: Raes Geert , Noël Wim , Beschin Alain , Brys Lea , de Baetselier Patrick , Hassanzadeh Gh. Gholamreza
Published: August 2003

Although it is well‐established that macrophages can occur in distinct activation states, the molecular characteristics of differentially activated macrophages, and particularly those of alternatively activated macrophages (aaMφ), are still poorly unraveled. Recently, we demonstrated that the expression of FIZZ1 and Ym is induced in aaMφ as compared with classically activated macrophages (caMφ), elicited in vitro or developed in vivo during infection with Trypanosoma brucei brucei. In the present study, we analyzed the expression of FIZZ1 and Ym in caMφ and aaMφ elicited during Trypanosoma congolense infection and show that the use of FIZZ1 and Ym for the identification of aaMφ is not limited to T. b. brucei infection and is independent of the organ sources from which macrophages are obtained. We also demonstrate that FIZZ1 can be used to discriminate between different populations of aaMφ. Furthermore, we studied the effects of various stimuli, and combinations thereof, on the expression of FIZZ1 and Ym in macrophages from different mouse strains and demonstrate that regulation of the expression of FIZZ1 and Ym in macrophages is not dependent on the mouse strain. Finally, we show that these genes can be used to monitor the macrophage activation status without the need to obtain pure macrophage populations.
Allergic Disease and Autoimmune Effectors Pathways
Authors: Rottem Menachem , Gershwin M. Eric , Shoenfeld Yehuda
Published: August 2003

Allergy and autoimmunity result from dysregulation of the immune system. Until recently, it was generally accepted that the mechanisms that govern these disease processes are quite disparate; however, new discoveries suggest possible common pathogenetic effector pathways. This review illustrates the concomitant presentation of these conditions and the potential relationship or common mechanism in some cases, by looking at the key elements that regulate the immune response in both allergic and autoimmunite conditions: mast cells, antibodies, T cells, cytokines, and genetic determinants. The parallel appearance of allergic and autoimmune conditions in the some patients may reveal that such aberrations of the immune system have a common pathophysiologic mechanism. Mast cells, which play a key role in allergic reactions, and the wealth of inflammatory mediators they express, make it likely that they have profound effects on many autoimmune processes. Activation of protein kinases by inflammatory cytokines and environmental stresses may contribute to both allergic and autoimmune diseases. The presence of autoantibodies in some allergic conditions suggests an autoimmune basis for these conditions. Because of the central role T cells play in immune reactivity, the T‐cell receptor (TCR) loci have long been considered important candidates for common disease susceptibility within the immune system such as asthma, atopy, and autoimmunity. Immunomodulation is the key to a successful treatment of allergic and autoimmune conditions.
Involvement of GANP in B Cell Activation in T Cell‐dependent Antigen Response
Authors: Sakaguchi Nobuo , Fujimura Satoru , Kuwahara Kazuhiko
Published: August 2003

Adaptive immunity is dependent on proliferation of antigen‐driven B cells for clonal expansion in germinal centers (GCs) against T cell‐dependent antigens (TD‐Ag), accompanied with somatic hypermutation of variable‐region gene and class switching of B cell antigen receptors. To study molecular mechanisms for B cell differentiation in GCs, we have identified and studied a 210 kDa GANP protein expressed in GC‐B cells. GANP has domains for MCM3‐binding and RNA‐primase activities and is selectively up‐regulated in centrocytes surrounded with follicular dendritic cells (FDCs) upon immunization with TD‐Ag in vivo and in B cells stimulated with anti‐CD40 monoclonal antibody in vitro, which suggested that GANP plays a certain important role in the maturation of immunoglobulin or selection of B cells in GC during the immune response to TD‐Ag. Since this up‐regulation has not been detected in T cells in GCs and in Concanavalin A‐stimulated T cells in vitro, selective function of GANP molecule on B cell proliferation and differentiation might exist.
Functional Tolerance is Maintained Despite Proliferation of CD4 T Cells after Encounter with Tissue‐derived Antigen
Authors: Ausubel Lara J. , Chodos Anna , Bekarian Nyree , Abbas Abul K. , Walker Lucy S. K.
Published: August 2003

Since negative selection in the thymus is incomplete, some self‐reactive T cells are able to mature and seed the periphery. To study how these T cells interact following encounter with the self‐protein they recognize in the periphery, we have developed an adoptive transfer system in which HEL‐specific TCR transgenic CD4 T cells are transferred to mice expressing HEL protein in the pancreas under the control of the rat insulin promoter. Here we show that after adoptive transfer of HEL‐specific T cells functional tolerance is maintained despite evidence that the T cells encounter and respond to pancreas‐expressed antigen. Even the provision of an additional activation stimulus by peripheral immunization with HEL protein is insufficient to induce the T cells to cause autoimmune tissue injury. However, in the presence of blocking anti‐CTLA‐4‐mAb, immunized adoptive transfer recipients rapidly developed diabetes. These data suggest that the CTLA‐4 pathway regulates the pathogenicity of antigen‐specific T cells following a peripheral activation stimulus.
Exposure to Environmental Antigens Induces the Development of Germinal Centers in Premature Neonates
Authors: Wittenbrink N. , Zemlin M. , Bauer K. , Berek C.
Published: August 2003

The immune response of the neonate is poor and is dependent on passive immunity provided by maternal Ig. However, here we show that exposure of the neonate to environmental antigens induces a germinal center (GC) reaction. In the peripheral blood of premature infants one finds IgG class switched B cells expressing a selected V‐gene repertoire. These data suggest that restrictions in the repertoire rather than immaturity of the immune system is responsible for the poor immune responses of the neonate.
Alcohol misuse and renal damage
Authors: CECCHIN EMANUELA , DE MARCHI SERGIO
Published: August 2003

Recent clinical and experimental studies have demonstrated that the habitual consumption of large amounts of ethanol has deleterious effects on the kidney. A variety of tubular defects have been described in patients with chronic alcoholism. Evidence is emerging that tubular dysfunction has an important pathophysiological role in a wide range of electrolyte and acid‐base disturbances commonly observed in these patients, and possibly in alcohol‐induced bone disease. These renal abnormalities are often reversible, disappearing with abstinence. However, since 1990 a few cases of a syndrome of acute tubular necrosis due to binge drinking of ethanol in the absence of other evident nephrotoxic mechanisms, or in association with the use of nonsteroidal anti‐inflammatory drugs, have been reported. A link between glomerulonephritis and alcoholism has become evident. IgA nephropathy has been demonstrated at autopsy in 64% of chronic alcoholics and, more recently, the association between alcoholism and postinfectious glomerulonephritis has been described. Structural and functional abnormalities of the kidney are reported with increasing frequency in the fetal alcohol syndrome seen in children who have been prenatally exposed to ethanol. In addition, over the last few years experimental studies in vitro or in animal models have provided information about the biochemical and molecular basis of alcohol‐induced injury to kidney. It is hoped that future experimental and clinical research will provide us with a more comprehensive knowledge of the mechanisms of renal damage in alcohol misuse.
The μ opioid receptor: from molecular cloning to functional studies
Authors: YU LEI
Published: August 2003

Opioids have been used and abused by humans for centuries. The μ opioid receptor represents the high affinity binding site for opioid narcotics with high abuse liability such as morphine, codeine and fentanyl. Heroin (diacetylmorphine), a semi‐synthetic derivative of morphine, crosses the blood‐brain barrier more readily than morphine due to its increased hydrophobicity. Once in the brain heroin is hydrolyzed to morphine, which acts at the μ opioid receptor and results in euphoria, thus conferring the reinforcing properties of heroin. Using molecular biology techniques, the μ opioid receptors from several species have been cloned. This article reviews recent progress in this area, with respect to the two major cellular functions of the μ opioid receptor: reduction of intracellular cAMP concentration by inhibiting adenylyl cyclase activity, and inhibition of neuronal firing by modulating membrane ion channels.