bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural nets and alphabets: introducing students to neural networks
Authors: Schweller K. G. , Plagman A. L.
Published: July 2004

Three student projects involving neural networks are described. The projects include recognizing handwritten letters of the alphabet, determining the orientation of an imaged line, and recognizing particular rooms of a house based on samples of furniture found in the rooms. All projects were run on a back propagation neural network program implemented in Modula-2. A description of the program is presented and a sample module for simulating the behavior of an OR gate is included as an appendix. The program has been successfully used in several Artificial Intelligence classes for classroom demonstrations and carrying out various cognitive science experiments.
Discrete-event simulation—a timley problem
Authors: Dorin P. M.
Published: July 2004

In this paper we discuss an exercise that is used in a first-year workshop to illustrate the main issues of discrete-event simulation programming. The problem is to make a program that determines all the times of the day at which a clock's hands form a straight angle.
A comprehensive mathematics curriculum for the computer science undergraduate program
Authors: Behforooz A. , Sharma O. P.
Published: July 2004

Mathematics requirements for computer science majors have been discussed in many papers and panels during the last twenty years. This paper, while reexamining this issue, presents a comprehensive view of the total mathematics requirement for a computer science undergraduate program rather than discuss some course contents in a piecemeal fashion. The time distribution among different topics, the depth of the topics to be covered and the minimal qualifications of the intructor to teach the courses are also included.
On teaching computer science using the three basic processes from the Denning report
Authors: Bagert D. J.
Published: July 2004

The recently-published final report of the ACM Task Force on the Core of Computer Science, commonly called the Denning Report, describes three processes which are inherent in all areas of computer science: theory, abstraction and design. This paper describes how this concept was used to teach the quicksort to high school computer science students.
Another breadth-first approach to CS I using python
Authors: Shannon Christine
Published: July 2004

In an effort to serve the needs of both majors and non-majors, the Computer Science Department at Centre College has restructured the CS I course so that it uses the language Python, devotes more attention to the Internet and the World Wide Web, addresses ethical and societal issues, and introduces students to programmable robots and an SQL database. This diverse course has been attractive to the students while still maintaining a strong emphasis on programming.
A reliable test for inclusion of a point in a polygon
Authors: Lewis Jerome L.
Published: July 2004

This paper takes a careful look at a well-known implementation of an algorithm that tests a point in the plane for inclusion in a given polygon. The implementation, coded in C++, appears in Robert Sedgewick's highly regarded book, Algorithms in C++, and has a number of flaws associated with special cases. The paper discusses the problems and a reliable implementation of the algorithm is developed.
Technological analysis and democratic policy-making
Authors: Whithed Marshall H.
Published: July 2004

The paper centers upon the implications of technical analytical methodologies, especially those which are computer-based, for public policy-making. A generalized analysis of the lack of suitable educational and experiental background of most public policy-makers is presented, and it is suggested that this lack makes it difficult for such officials to adequately evaluate technical analyses. Means to ameliorate this problem are discussed, and a model of policy-maker/computer methodology interface is presented. The example used is based on a computer simulation model and related methodologies which are presently developed for HUD to study New Town fiscal and economic viability.
A systematic approach to identifying a safe subset for safety-critical software
Authors: Bhansali P. V.
Published: July 2004

Programming languages and design methodologies need to be tailored before they can be used in safety-critical software. This tailoring is done via subsetting which excludes certain features that are hard to use and verify. A systematic approach to subsetting is described with examples from real-world applications.
Service learning models connecting computer science to the community
Authors: Traynor Carol , McKenna Maria
Published: July 2004

Service learning is an educational experience that enables students to apply material learned in the classroom by volunteering in a real-world situation. This paper provides a brief review of service learning and describes two models that the computer science department at Saint Anselm College implemented successfully.
Report on the Engineering Federated Information Systems 2003 workshop (EFIS 2003)
Authors: Wyss C. M. , James A. , Hasselbring W. , Conrad S. , Höpfner Hagen
Published: July 2004

This paper summarizes the EFIS 2003 workshop, held in Coventry, U.K. in July, as part of Coventry University's Data Horizons Week. Major research issues discussed include metadata/ontologies, integration frameworks, data quality and evolution, and mobile interfaces. Topics for future work include evolution, expressiveness, maintenance, and dissemination of FIS.
Minicomputer assisted instruction
Authors: Lewis T. G.
Published: July 2004

Even though minicomputers are widely used in industry they are slow to gain acceptance in computer science education. However, because of its increasingly great impact on industry and its potential as a teaching device, the minicomputer should be considered a part of the computer science curriculum. This paper proposes a minicomputer laboratory course at the lower division level emphasizing hands-on use, fundamental computer concepts in conjunction with "computer lore", and problems peculiar to machines. Also, an upper division course is suggested which emphasizes demonstration of advanced programming techniques.
Techniques for computer science teachers
Authors: Abshire Gary M.
Published: July 2004

This paper lists the skills needed to teach computer science effectively in a university environment. Practical guidance on what constitutes good instruction and creative teaching is given. Included are ideas on stating the prerequisite and objective of the course; organizing your course; making your own transparencies; tackling preliminary arrangements; using the chalkboard and overhead projector; delivering the presentation; testing; and knowing and helping your students.
Teaching computer applications using computer cases
Authors: Lovas Charles M.
Published: July 2004

The case method of teaching is used to encourage continued use of computers and programming in a student's major area after the initial course(s) in computer programming. The computer case demonstrates the real-life need for the computer application, promotes independent problem-solving and computer code generation, and exposes the student to a broad spectrum of educational experiences. The flexibility of classroom operation provided to the instructor by the case method permits efficient introduction of supplementary content material and provides the instructor with the opportunity to custom classroom discussion to elicit the maximum change in student performance with a minimum of time.The teaching of extended program applications in courses using the computer, beyond the basic computer programming courses, suffers in many curricula for a number of reasons: lack of student interest, student "fear" of programming, lack of instructor training in use of the computer, inability of instructors to relate the computer application to an existing need in real-life, excess time and effort for major project programming, and others. One approach to the teaching of computer applications which can alleviate many of these difficulties is the use of computer cases.
A data-oriented introduction to program design
Authors: Collins William J.
Published: July 2004

Stepwise refinement is an invaluable analytic tool for solving complex problems, but it is somewhat artificial for the simple problems encountered in the first half of an introductory programming course. This paper describes an alternate process which still provides for a gradual transition from a problem to an algorithm which solves the problem. Each algorithm, which is unambiguous and English-like, is synthesized from sample data and can be routinely translated into a (structured) program.
Vertical integration in group learning
Authors: Parslow R. D.
Published: July 2004

This paper is mainly concerned with the teaching of Computer Science to first year (freshman) students. The method outlined is an attempt to change their generally 'convergent' attitudes into a more 'divergent' way of tackling problems, so that open-ended solutions are presented rather than the answer.
Assembly language at Potsdam College
Authors: Tenny Ted
Published: July 2004

Assembly language is reconciled with high-level programming concepts through the use of subroutines, designed by the student with PL/I as a meta-language and implemented in assembly language on the IBM 360. The student's subroutine is linked to a grading program, prepared by the instructor, which generates pseudo-random test data for a sequence of cases, calls the student's subroutine, and prints the results.
System description as a tool for teaching programming
Authors: Mathiassen Lars
Published: July 2004

The paper shows by an example how system description can be used as a starting-point for teaching programming to beginners. The system description techniques used are based upon the philosophy developed within the DELTA project. In each phase of the teaching process a different language tool is used. In the first phase we use a very informal system description tool. In the second phase we use a more formalized system description tool, while still allowing a certain amount of informal language. Finally in the third phase a totally formalized system description tool--in this case the programming language SIMULA--is used.
A hardware course for a software curriculum
Authors: Cook Robert N.
Published: July 2004

The computer science program at Central Michigan University is a predominantly software oriented program with approximately 400 undergraduate majors and minors. One "hardware" course, which is described in this paper, is required of all majors. One hundred ten students were enrolled in the course during the Fall 1979 Semester. Concepts covered include logic circuit design, arithmetic and logic unit design/operation, and the architecture of various computers.A logic demonstration board has been developed as a teaching aid for the course, as no laboratory is currently available. Five other architecture/design courses are available in the department, although they are taken primarily by graduate students.
The feasibility of personal computers versus a minicomputer for a computer science program
Authors: Goldbogen Goef , Williams G. H.
Published: July 2004

This paper reports on the experiences at Union University in using a minicomputer based time-sharing facility versus a loosely-coupled microcomputer based facility. These two facilities are the only computer resources used by two disjoint academic populations. Comparisons are drawn on the acquisition costs, staffing, and operating costs. The microcomputer system is an inexpensive, viable alternative.
Upgrading educational programs in computer information systems
Authors: Ray H. N. , Guynes C. S.
Published: July 2004

Business Computer-Based Information Systems have been, and are, continuing to experience rapid change. Current state-of-the art techniques include: (1) "Distributed Processing and Networks," (2) "Real-Time Transaction Processing," (3) "Decision Support Systems," (4) "On-line Data Preparation," (5) "Highly Integrated Application Systems supported by a common base of data," and (6) the ever increasing use of "Database Management Systems." These complex, sophisticated techniques are being employed in business and industry today and demand highly trained, qualified personnel. And yet when we look at educational programs these concepts are usually covered in theory only with few opportunities for application. This lack of application leaves a void in the expertise of most graduates.
Program synthesis as a tool for teaching programming
Authors: Hirshfield Stuart H.
Published: July 2004

An introductory programming course is described the content and format of which are based on the use of a program synthesizer. The synthesizer is seen as a useful and effective tool for students and teachers alike, particularly in a course with a problem-solving orientation. Common reservations about the use of such a tool in an introductory course are discussed in light of our experiences over the past two years.
Managing programming assignments in a RSTS/E account group
Authors: Paquet Brother Ernest
Published: July 2004

This article describes a multiprogramming situation in which one or more leaders must access sequences of normally protected accounts and files on a regular basis.The constraints of the situation, together with the peculiar advantages of the software available, led to what may be a novel, certainly a much appreciated bit of programming.
A proposed graduate course in automatic software generation
Authors: Pope Wendell L.
Published: July 2004

The backlog of demand for applications software is exceeding the productivity of programmers using conventional procedural languages. One approach to solving this problem is increasing programmer productivity through the use of automatic software generation systems. This paper presents the background of the software crunch, the reasons conventional programming languages are not expected to meet it, and the possibility of the state of the art being adequate to support a graduate course in automatic software generation.
Distinct effects of SP-B and SP-C on the uptake of surfactant-like liposomes by alveolar cells in vivo and in vitro
Authors: Poelma D. L. H. , Zimmermann L. J. , van Cappellen W. A. , Haitsma J. J. , Lachmann B. , van Iwaarden J. F.
Published: July 2004

The effects of surfactant protein B (SP-B) and SP-C on the uptake of surfactant-like liposomes by alveolar type II cells and alveolar macrophages were studied both in vivo and in vitro. In vivo, mechanically ventilated rats were intratracheally instilled with fluorescently labeled liposomes that had SP-B and/or SP-C incorporated in different concentrations. Consequently, the alveolar cells were isolated, and cell-associated fluorescence was determined using flow cytometry. The results show that the incorporation of SP-B does not influence the uptake, and it also does not in the presence of essential cofactors. The inclusion of SP-C in the liposomes enhanced the alveolar type II cells at a SP-C to lipid ratio of 2:100. If divalent cations (calcium and magnesium) were present at physiological concentrations in the liposome suspension, uptake of liposomes by alveolar macrophages was also enhanced. In vitro, the incorporation of SP-B affected uptake only at a protein-to-lipid ratio of 8:100, whereas the inclusion of SP-C in the liposomes leads to an increased uptake at a protein-to-lipid ratio of 1:100. From these results, it can be concluded that SP-B is unlikely to affect uptake of surfactant, whereas SP-C in combination with divalent cations and other solutes are capable of increasing the uptake.
Levodopa with carbidopa diminishes glycogen concentration, glycogen synthase activity, and insulin-stimulated glucose transport in rat skeletal muscle
Authors: Smith Jill L. , Ju Jeong-Sun , Saha Bithika M. , Racette Brad A. , Fisher Jonathan S.
Published: July 2004

We hypothesized that levodopa with carbidopa, a common therapy for patients with Parkinson's disease, might contribute to the high prevalence of insulin resistance reported in patients with Parkinson's disease. We examined the effects of levodopa-carbidopa on glycogen concentration, glycogen synthase activity, and insulin-stimulated glucose transport in skeletal muscle, the predominant insulin-responsive tissue. In isolated muscle, levodopa-carbidopa completely prevented insulin-stimulated glycogen accumulation and glucose transport. The levodopa-carbidopa effects were blocked by propranolol, a β-adrenergic antagonist. Levodopa-carbidopa also inhibited the insulin-stimulated increase in glycogen synthase activity, whereas propranolol attenuated this effect. Insulin-stimulated tyrosine phosphorylation of insulin receptor substrate (IRS)-1 was reduced by levodopa-carbidopa, although Akt phosphorylation was unaffected by levodopa-carbidopa. A single in vivo dose of levodopa-carbidopa increased skeletal muscle cAMP concentrations, diminished glycogen synthase activity, and reduced tyrosine phosphorylation of IRS-1. A separate set of rats was treated intragastrically twice daily for 4 wk with levodopa-carbidopa. After 4 wk of treatment, oral glucose tolerance was reduced in rats treated with drugs compared with control animals. Muscles from drug-treated rats contained at least 15% less glycogen and ∼50% lower glycogen synthase activity compared with muscles from control rats. The data demonstrate β-adrenergic-dependent inhibition of insulin action by levodopa-carbidopa and suggest that unrecognized insulin resistance may exist in chronically treated patients with Parkinson's disease.
Reduction in airway hyperresponsiveness to methacholine by the application of RF energy in dogs
Authors: Danek Christopher J. , Lombard Charles M. , Dungworth Donald L. , Cox P. Gerard , Miller John D. , Biggs Michael J. , Keast Thomas M. , Loomas Bryan E. , Wizeman William J. , Hogg James C. , Leff Alan R.
Published: July 2004

We delivered controlled radio frequency energy to the airways of anesthetized, ventilated dogs to examine the effect of this treatment on reducing airway narrowing caused by a known airway constrictor. The airways of 11 dogs were treated with a specially designed bronchial catheter in three of four lung regions. Treatments in each of the three treated lung regions were controlled to a different temperature (55, 65, and 75°C); the untreated lung region served as a control. We measured airway responsiveness to local methacholine chloride (MCh) challenge before and after treatment and examined posttreatment histology to 3 yr. Treatments controlled to 65°C as well as 75°C persistently and significantly reduced airway responsiveness to local MCh challenge ( P ≤ 0.022). Airway responsiveness (mean percent decrease in airway diameter after MCh challenge) averaged from 6 mo to 3 yr posttreatment was 79 ± 2.2% in control airways vs. 39 ± 2.6% ( P ≤ 0.001) for airways treated at 65°C, and 26 ± 2.7% ( P ≤ 0.001) for airways treated at 75°C. Treatment effects were confined to the airway wall and the immediate peribronchial region on histological examination. Airway responsiveness to local MCh challenge was inversely correlated to the extent of altered airway smooth muscle observed in histology ( r = −0.54, P < 0.001). We conclude that the temperature-controlled application of radio frequency energy to the airways can reduce airway responsiveness to MCh for at least 3 yr in dogs by reducing airway smooth muscle contractility.
Calculations on some sequence spaces
Authors: de Malafosse Bruno
Published: July 2004

We deal with space of sequences generalizing the well‐known
spaces , c∞(λ, μ),
replacing the operators C(λ) and Δ(μ) by their
transposes. We get generalizations of results concerning the
strong matrix domain of an infinite matrix A.
Reservicing some customers in M/G/1 queues under three disciplines
Authors: Salehi-Rad M. R. , Mengersen K. , Shahkar G. H.
Published: July 2004

Consider an M/G/1 production line in which a production item is failed with some probability and is then repaired. We consider three repair disciplines depending on whether the failed item is repaired immediately or first stockpiled and repaired after all customers in the main queue are served or the stockpile reaches a specified threshold. For each discipline, we find the probability generating function (p.g.f.) of the steady‐state size of the system at the moment of departure of the customer in the main queue, the mean busy period, and the probability of the idle period.
A characteristic initial value problem for a strictly hyperbolic system
Authors: Iraniparast Nezam
Published: July 2004

Consider the system Autt + Cuxx = f(x, t), (x, t) ∈ T for
u(x, t) in ℝ2, where A and C are real constant
2 × 2 matrices, and f is a continuous function in
ℝ2. We assume that detC ≠ 0 and that the system
is strictly hyperbolic in the sense that there are four distinct
characteristic curves Γi, i = 1, …, 4, in xt‐plane
whose gradients (ξ1i, ξ2i) satisfy
. We allow the characteristics of the system to be given
by dt/dx = ±1

and dt/dx = ±r, r ∈ (0, 1). Under special
conditions on the boundaries of the region T = {(x, t) ≤ t ≤ 1, (−1 + r + t)/r ≤ x ≤ (1 + r − t)/r}, we will show that the system has a unique C2

solution in T.
On the Beurling algebras Aα+(𝔻)—derivations and extensions
Authors: Steiniger Holger
Published: July 2004

Based on a description of the squares of cofinite primary ideals of , we prove the following results: for α ≥ 1, there exists a derivation from into a finite‐dimensional module such that this derivation is unbounded on every dense subalgebra; for m ∈ ℕ and α ∈ [m, m + 1), every finite‐dimensional extension of splits algebraically if and only if α ≥ m + 1/2.
IL-2 and IL-10 Production by Human CD4+T Cells Is Differentially Regulated by p38: Mode of Stimulation-Dependent Regulation of IL-2
Authors: Veiopoulou Christina , Kogopoulou Olga , Tzakos Evaggelos , Mavrothalassitis George , Mitsias Dimitris , Karafoulidou Anastasia , Paliogianni Fotini , Moutsopoulos Haralampos M. , Thyphronitis George
Published: July 2004

Antigenic stimulation of T cells initiates a complex series of intracellular signaling pathways that target and activate different cytokine genes. The participation of mitogen-activated protein kinases (MAPKs) in these processes has not been studied thoroughly and in some instances conflicting results have been reported. Here we have examined the role of p38 MAPK on IL-2 and IL-10 production following activation of human CD4+ T cells or of the leukemic cell line Hut-78, with either plate-bound anti-CD3 in the presence or absence of soluble anti-CD28 (plCD3, plCD3/sCD28), or with cross-linked anti-CD3 and anti-CD28 (crsCD3+CD28), or with PMA plus ionomycin. Pharmacological inhibition of the p38 pathway with either SB203580, SB202190, or SKF86002 strongly downregulated IL-10 production by T cells stimulated with any of the above treatments. In contrast the effect of p38 inhibition on IL-2 was stimulus dependent. Thus, p38 inhibition strongly upregulated IL-2 production (up to 10-fold) in the plCD3- and plCD3/sCD28-stimulated cultures while it had minimal or no effect in the other two stimulation protocols. Intracellular and mRNA levels of IL-2 and IL-10 were also upregulated and downregulated, respectively, by p38 inhibitors in the plCD3/sCD28-stimulated CD4+ T cells. Also, the induction of IL-2 and the parallel suppression of IL-10 by p38 inhibitors were independent of the balance between these two cytokines, as demonstrated by the addition of exogenous IL-10 or blocking anti-IL-10 antibody in CD4+ and Hut-78 cell cultures. These results show that p38 acts as a molecular switch that changes the balance between IL-2 and IL-10. This is especially important considering the opposing role of these cytokines in peripheral immune tolerance.
Th1 and Th2 Serum Cytokine Profiles Characterize Patients with Hashimoto’s Thyroiditis (Th1) and Graves’ Disease (Th2)
Authors: Phenekos Costas , Vryonidou Andromachi , Gritzapis Angelos D. , Baxevanis Constantinos N. , Goula Margarita , Papamichail Michael
Published: July 2004

Objectives: The aim of this study was to document the pattern of immune response, assessed by the measurement of both Th1 and Th2 serum cytokines, in patients suffering from autoimmune thyroid disease and toxic nodular goiter. Methods: Both Th1 and Th2 serum cytokine levels were assayed in patients suffering from Graves’ disease (GD, n = 25), Hashimoto’s thyroiditis (HT, n = 21), and toxic nodular goiter (TNG, n = 7) and compared with corresponding levels of 25 healthy controls. Serum concentrations of IL-2, IL-1β, INF-γ, TNF-α, IL-12, IL-15, IL-10, IL-18, IL-4 and IL-5 were assayed in fasting serum samples. Results: It was found that patients with HT had higher IL-2 serum levels (12.16 ± 0.66 pg/ml) compared to patients with TNG (9.25 ± 0.84 pg/ml), GD (7.86 ± 0.30 pg/ml) and controls (7.36 ± 0.45 pg/ml; p = 0.0001), higher INF-γ levels (7.60 ± 0.33 pg/ml) compared to patients with TNG (5.77 ± 0.55 pg/ml), GD (5.74 ± 0.24 pg/ml) and controls (5.09 ± 0.27 pg/ml; p = 0.0009), higher IL-12 levels (3.57 ± 0.19 pg/ml) compared to patients with TNG (2.57 ± 0.21 pg/ml), GD (2.48 ± 0.13 pg/ml) and controls (2.59 ± 0.23 pg/ml; p = 0.004), and higher IL-18 levels (27.52 ± 1.75 pg/ml) compared to patients with TNG (18.71 ± 2.24 pg/ml), GD (15.44 ± 1.39 pg/ml) and controls (15.16 ± 1.62 pg/ml; p = 0.0002). In contrast, patients with GD had higher serum levels of IL-4 (4.11 ± 0.33 pg/ml) compared to patients with HT (3.0 ± 0.16; p = 0.02) and higher IL-5 levels (4.22 ± 0.30 pg/ml) compared to patients with TNG (3.21 ± 0.58 pg/ml), HT (2.75 ± 0.16 pg/ml) and controls (2.0 ± 0.19 pg/ml; p = 0.0001). Patients had lower IL-1β serum levels (TNG 2.45 ± 0.20, HT 2.52 ± 0.14, GD 2.68 ± 0.12 pg/ml) compared to controls (3.6 ± 0.20 pg/ml; p = 0.008). Conclusions: The above findings suggest that a Th1 pattern of immune response characteristic of cellular immunity is dominant in HT, whereas the predominance of Th2 cytokines in GD indicates a humoral pattern of immune reaction.
Adrenergic Modulation of Survival and Cellular Immune Functions during Polymicrobial Sepsis
Authors: Oberbeck Reiner , Schmitz Daniel , Wilsenack Klaus , Schüler Marc , Pehle Birthe , Schedlowski Manfred , Exton Michael S.
Published: July 2004

Objective: An immunomodulatory effect of epinephrine has been reported that is supposed to be mediated via β-adrenergic receptors. The effect of epinephrine and/or β-adrenergic blockade on cellular immune functions during systemic inflammation has not yet been investigated. Methods: Male NMRI mice were treated with either an infusion of epinephrine (0.05 mg/kg/h i.p.), administration of the nonselective β-adrenoceptor antagonist propranolol (0.5 mg/kg s.c.), or a combination of epinephrine and propranolol after induction of a polymicrobial sepsis by cecal ligation and puncture. Forty-eight hours thereafter survival and cellular immune functions (splenocyte proliferation, splenocyte apoptosis and cytokine release, distribution of leukocyte subsets) were determined. Results: Infusion of epinephrine did not affect lethality of septic mice but induced alterations of splenocyte apoptosis, splenocyte proliferation and IL-2 release and was associated with profound changes of circulating immune cell subpopulations. Treatment with propranolol augmented the epinephrine-induced increase of splenocyte apoptosis, did not affect the decrease of splenocyte proliferation and IL-2 release, augmented the release of IL-6 and antagonized the mobilization of natural killer cells observed in epinephrine-treated animals. Furthermore, these immunologic alterations were accompanied by a significant increase of sepsis-induced mortality. Coadministration of propranolol and epinephrine augmented the propranolol-induced changes of splenocyte apoptosis and IL-6 release and was associated with the highest mortality of septic mice. Conclusion: Epinephrine infusion modulated cellular immune functions during systemic inflammation without an impact on survival. A pharmacologic β-adrenergic blockade partly augmented the epinephrine-induced immune alterations and was associated with a pronounced increase of mortality. This effect was further augmented by a combination of epinephrine infusion and β-adrenergic blockade. These data indicate that adrenergic mechanisms modulate cellular immune functions and survival during sepsis, with these effects being mediated via α- and β-adrenergic pathways.
Comparative Study of gp130 Cytokine Effects on Corticotroph AtT-20 Cells – Redundancy or Specificity of Neuroimmunoendocrine Modulators?
Authors: Auernhammer Christoph J. , Kopp Florian B. , Vlotides George , Dorn Franziska , Isele Nicola B. , Spöttl Gerald , Cengic Neziha , Weber Matthias M. , Senaldi Giorgio , Engelhardt Dieter
Published: July 2004

Objective: This comparative in vitro study examined the effects of all known gp130 cytokines on murine corticotroph AtT-20 cell function. Methods: Cytokines were tested at equimolar concentrations from 0.078 to 10 nM. Tyrosine phosphorylation of the signal transducer and activator of transcription (STAT)3 and STAT1, the STAT-dependent suppressor of cytokine signaling (SOCS)-3 promoter activity, SOCS-3 gene expression, STAT-dependent POMC promoter activity and adrenocorticotropic hormone (ACTH) secretion were determined. Results: Leukemia inhibitory factor (LIF), human oncostatin M (OSM) and cardiotrophin (CT)-1 (LIFR/gp130 ligands), as well as ciliary neurotrophic factor (CNTF) and novel neurotrophin-1/B-cell stimulating factor-3 (CNTFRα/LIFR/gp130 ligands) are potent stimuli of corticotroph cells in vitro. In comparison, interleukin (IL)-6 (IL-6R/gp130 ligand) and IL-11 (IL-11R/gp130 ligand) exhibited only modest direct effects on corticotrophs, while murine OSM (OSMR/gp130 ligand) showed no effect. Conclusion: (i) CNTFR complex ligands are potent stimuli of corticotroph function, comparable to LIFR complex ligands; (ii) IL-6 and IL-11 are relatively weak direct stimuli of corticotroph function; (iii) differential effects of human and murine OSM suggest that LIFR/gp130 (OSMR type I) but not OSMR/gp130 (OSMR type II) are involved in corticotroph signaling. (iv) CT-1 has the hitherto unknown ability to stimulate corticotroph function, and (v) despite redundant immuno-neuroendocrine effects of different gp130 cytokines, corticotroph cells are preferably activated through the LIFR and CNTFR complexes.
Effects of Neurointermediate Pituitary Lobectomy on Humoral and Cell-Mediated Immune Responses in the Rat
Authors: Quintanar-Stephano Andrés , Kovacs Kalman , Berczi Istvan
Published: July 2004

Objective: Chronic stress is characterized by an increased activity of the hypothalamic-pituitary-adrenocortical axis and decreased humoral and cell-mediated immune responses. In the rat, corticosterone is the principal natural immune suppressor. Neurointermediate pituitary lobectomy () in rats induces diabetes insipidus and protracted increases in basal adrenocorticotropin and corticosterone plasma levels, a situation that resembles chronic stress. In this paper, we evaluated the effects of on humoral (hemagglutinin titers and footpad swelling to sheep red blood cells – SRBC) and cell-mediated immune responses (contact hypersensitivity to dinitrochlorobenzene). Methods: The studies were conducted on Wistar rats (body weight 150–200 g) 3 weeks after surgery. For comparisons, nonoperated control rats were used. Results: resulted in an increased water intake. Body weight gain and adrenal, thymus, and spleen weights were within the range of nonoperated controls. Eight days after SRBC immunizations a second SRBC injection into the footpad resulted in a decreased swelling response in rats. The hemagglutinin titers were also reduced in the rats. Conclusions: These results indicate that: (1) reduces humoral immune responses and decreases the cell-mediated immune response; (2) the immune alterations are most likely due to the increased activity of the hypothalamic-pituitary-adrenocortical axis induced by , and (3) animals constitute a valuable paradigm to study hypothalamic-pituitary-immune interactions.
Corticosterone Changes in Response to Stressors, Acute and Protracted Actions of Tumor Necrosis Factor-α, and Lipopolysaccharide Treatments in Mice Lacking the Tumor Necrosis Factor-α p55 Receptor Gene
Authors: Hayley Shawn , Kelly Owen , Anisman Hymie
Published: July 2004

Systemic administration of the proinflammatory cytokine, tumor necrosis factor-α (TNF-α), has acute as well as sensitizing effects on behavioral and neurochemical functioning. Objectives: As many of the central consequences of TNF-α are mediated by its p55 receptor, the present investigation determined the role of this receptor on the plasma corticosterone increase associated with the acute TNF-α treatment and the sensitized response evident upon reexposure to the cytokine. Moreover, the role of p55 in the provocation of corticosterone release engendered by lipopolysaccharide (LPS) and psychogenic stressors (noise or restraint) was also determined. Methods: Plasma corticosterone levels were determined in wild-type and p55-deficient mice that received systemic treatments with TNF-α and LPS, as well as exposure to auditory and restraint stressors. Results: Mice deficient for p55 displayed a greatly attenuated plasma corticosterone response to TNF-α irrespective of whether they had been previously exposed to the cytokine. In contrast, p55 deletion did not affect corticosterone responses elicited by LPS and by stressors. Conclusions: It appears that although p55 modulates the corticosterone-inducing effects of TNF-α, the receptor does not play a critical role in the activation of the HPA axis by ‘traditional’ psychogenic stressors (noise, restraint) or systemic endotoxin challenge.
Differential Responses of Circulating Prolactin, GH, and ACTH Levels and Distribution and Activity of Submaxillary Lymph Node Lymphocytes to Calorie Restriction in Male Lewis and Wistar Rats
Authors: Lopez-Varela Sara , Chacón Fernando , Cano Pilar , Arce Agustín , Esquifino Ana I.
Published: July 2004

Objectives: Calorie restriction has been associated with anorexia in growing individuals, but the mechanisms involved are not known. Also, the effects of carbohydrates and lipid restriction in growing individuals were not studied. The aim of this study was to determine whether 66% calorie restriction (lipids and carbohydrates) differentially affects growing rats of the Wistar or Lewis strains. Methods: Growing male Wistar and Lewis rats were subjected to 66% calorie restriction for 4 weeks. Plasma prolactin, growth hormone (GH), and adrenocorticotropic hormone (ACTH) levels were measured by specific radioimmunoassays. Likewise, lymphocytes from submaxillary lymph nodes were aseptically obtained to study absolute number of lymphocytes, cell surface markers (CD4+, CD8+, CD4+CD8+, B, and T cells), and proliferation. Results: The body weight gain was lower in Lewis than in Wistar rats and was blunted in both strains by calorie restriction. Wistar and Lewis rats exhibited differential patterns of plasma prolactin, ACTH, and GH levels as well as proliferative capacities of T and B cells and their distribution in the submaxillary lymph nodes. Calorie restriction increased plasma prolactin and ACTH levels in Lewis as compared with Wistar rats. However, the plasma GH levels were diminished in both strains of rats by calorie restriction. All changes in plasma prolactin ACTH and GH levels seemed to correlate with the modifications observed in the distributions of T and B subsets in the submaxillary lymph nodes as well as in their proliferative capacity. Conclusions: Calorie restriction differentially modifies the secretory patterns of prolactin, GH, and ACTH in Lewis and in Wistar rats. These changes may explain, at least in part, the associated modifications in the proliferative capacity of submaxillary lymph node lymphocytes and in their distribution.
Effects of Fentanyl on Natural Killer Cell Activity and on Resistance to Tumor Metastasis in Rats
Authors: Shavit Yehuda , Ben-Eliyahu Shamgar , Zeidel Alexander , Beilin Benzion
Published: July 2004

Objectives: Opiates, which serve an integral role in anesthesia, suppress immune function, particularly natural killer cell cytotoxicity (NKCC). NK cells play an important role in tumor and metastasis surveillance. We reported that large-dose fentanyl anesthesia induced prolonged suppression of NKCC in patients undergoing abdominal surgery. The immune modulatory effects of opiates may depend on the interaction between dose and time of administration. The present study examined the effects of different doses of fentanyl, administered at different time points relative to tumor inoculation, on NKCC and on experimental tumor metastasis in rats. Methods: Fischer 344 rats were injected with low or high doses of fentanyl, 6 or 2 h before, simultaneously with or 1 h after being inoculated intravenously with MADB106 tumor cells. Lung tumor retention (LTR) was assessed 4 h after, and lung tumor metastases were counted 3 weeks after tumor inoculation. NKCC was assessed 1 h after the fentanyl injection. Results: At all time points, except 6 h before tumor inoculation, fentanyl (0.1–0.3 mg/kg) induced a dose-dependent increase in MADB106 LTR (2.3- to 74-fold). An intermediate dose of fentanyl (0.15 mg/kg) doubled the number of lung metastasis, and, within animal, suppressed NKCC and increased MADB106 LTR in a correlated manner. Conclusion: These findings indicate that fentanyl suppresses NKCC and increases the risk of tumor metastasis. Suppression of NK cells at a time when surgery may induce tumor dissemination can prove to be critical to the spread of metastases. It is suggested that the acute administration of a moderate dose of opiates during surgery should be applied cautiously, particularly in cancer patients.
Differential Effects of Rapid Eye Movement Sleep Deprivation and Immobilization Stress on Blood Lymphocyte Subsets in Rats
Authors: Velazquez-Moctezuma Javier , Dominguez-Salazar Emilio , Cortes-Barberena Edith , Najera-Medina Oralia , Retana-Marquez Socorro , Rodriguez-Aguilera Ernesto , Jiménez-Anguiano Anabel , Cortes-Martinez Leticia , Ortiz-Muñiz Rocio
Published: July 2004

Objectives: There is growing evidence of the relationship between sleep and the immune response. Studies aimed at elucidating the function of rapid eye movement (REM) sleep have found it difficult to separate the effects due to REM sleep deprivation and the effects due to the stress produced by the deprivation procedure. It has been claimed that immobilization is the main stressor that the animals have to face during the deprivation process. In this study, we analyzed the effects of short-term (24 h) and long-term (240 h) REM sleep deprivation on the distribution of lymphocyte subsets in the peripheral blood of rats. In addition, these effects were compared with those obtained after both short- and long-term stress by immobilization. Methods: Lymphocyte population bearing surface markers such as CD5 (T cells), CD45RA (B cells), CD4 (T helper/inducer cells), CD8 (T suppressor/cytotoxic cells) and CD161 (NK cells) were analyzed using monoclonal antibodies. Lymphocyte subsets were assessed by flow cytometry. Results: Both short- and long-term REM sleep deprivation decreased the percentage of T lymphocytes and induced a significant increase in NK cells. Short-term immobilization induced only a significant increase in the percentage of B lymphocytes and a decrease in the percentage of T lymphocytes, while long-term immobilization did not elicit any change. Conclusion: The present results support the notion that REM sleep deprivation and immobilization stress each exert particular effects on the immune system. These data suggest that the characteristics of the immune response will depend on the nature of the behavioral manipulation.
Electroacupuncture Enhancement of Natural Killer Cell Activity Suppressed by Anterior Hypothalamic Lesions in Rats
Authors: Hahm Eu-Teum , Lee Jong-Ju , Lee Won-Kyu , Bae Hyun-Soo , Min Byung-Il , Cho Young-Wuk
Published: July 2004

Background/Objective: Neuroendocrine hormones are derived from the hypothalamus. The central nervous system, particularly the hypothalamus, is capable of modulating the cytolytic activity of adherent natural killer (NK) cells. In addition, electroacupuncture (EA) stimulation of the Zusanli (ST36) acupoint enhances splenic NK cell and cytokine activities in rats. However, it is still unclear whether the anterior hypothalamus affects this immunomodulation. Therefore, the aim of the present study was to examine the effect of EA stimulation at the Zusanli acupoint on the NK cell activity modulated by an anterior hypothalamic area lesion. Methods: Male Sprague-Dawley rats were used. Lesions were placed by means of a direct current through a concentric electrode. The electric acupuncture stimulation was delivered for 30 min per each experiment at the right ST36 acupoint with an electrical stimulator. The NK cell activity of the spleen was measured by a fluorescence assay. Results: The NK cell activity was significantly reduced on the 2nd day after the lesion, but was restored to that of the sham group by the 7th day. However, when EA was applied for 2 days after the operation, the NK cell activity of the lesion group was restored to that of the sham group. After 7 days of EA, the NK cell activity of the lesion group was slightly higher than that of the sham group. Conclusion: From these results, we can suggest that EA enhances or restores the NK cell activity suppressed by an anterior hypothalamic area lesion.
Benign Multiple Sclerosis Is Characterized by a Stable Neuroimmunologic Network
Authors: Haase Claus G. , Faustmann Pedro M.
Published: July 2004

Objectives: Patients diagnosed with multiple sclerosis (MS) but without disability (Expanded Disability Status Scale score <2) form a specific group within those patients suffering from relapsing-remitting MS. Several neuroimmunologic effectors, including cytokines and melatonin, are known for their influence on the initiation of relapses and progression of the disease. Methods: We evaluated 41 female patients with benign MS with respect to their clinical course, treatments and neuroimmunological parameters, including cytokines and melatonin. One subgroup was followed up for 7 years, and another group was evaluated during acute clinical relapse. Results: The benign MS course in this homogeneous group of young patients was demonstrated by mild disease progression in 16% over 7 years. Initially, patients treated with azathioprine (AZA) revealed significantly reduced melatonin serum levels (p = 0.04) compared to untreated patients, but not at follow-up. During acute relapse, treatment with corticosteroids (CS) resulted in increased levels of type 2 cytokines as well as reduced type 1 cytokine levels. Conclusions: Our study supports the functional role of CS acting as an antiinflammatory protagonist during MS relapse, by inducing a shift towards predominance of type 2 cytokines. AZA showed a more subtle modulation of immune functions, reflected by reduced levels of the immune active hormone melatonin. During follow-up, it became apparent that stabilized levels of the interacting Th1/Th2-derived cytokines and melatonin are maintained in concordance with the benign course of MS. These findings are in accordance with the hypothesis that benign MS is characterized by a balanced cytokine and neuroendocrine network, which is supported by immune-modulating therapies.
Uveitis: A Potentially Blinding Disease
Authors: Durrani O.M. , Meads C.A. , Murray P.I.
Published: July 2004

Uveitis (intraocular inflammation) is a potentially blinding group of, probably autoimmune, conditions predominantly occurring in the working age group. Although the aetiology is unknown in most cases, many patients have an associated underlying systemic disease. Central vision loss, in the form of cystoid macular oedema, is the commonest type of visual impairment. Although historical incidence and prevalence data exists, little is known about the degree of vision loss experienced, and the social and financial consequences of having temporary or permanent visual impairment in this age group. The literature is also full of uncontrolled studies and case reports of different modalities of drug therapy for uveitis. This article attempts to raise the awareness of uveitis as an important sight-threatening group of conditions by highlighting the paucity of evidence-based data on epidemiological, quality of life, socioeconomic, and therapeutic aspects.
Ocular Blood Flow Velocity Determined by Color Doppler Imaging in Diabetic Retinopathy
Authors: Gračner Tomaž
Published: July 2004

Purpose: To measure and investigate changes of blood flow velocity by color Doppler imaging in the ophthalmic artery (OA), central retinal artery (CRA) and short posterior ciliary arteries (PCA) in diabetic retinopathy (DR) and to compare the results with those in healthy control subjects. Methods: In this investigation we included 44 eyes of 44 diabetic patients with different stages of DR forming group NPDR (11 eyes with mild and 11 eyes with moderate nonproliferative DR) and group SNPDR/PDR (19 eyes with severe nonproliferative and 3 eyes with proliferative DR) and 22 eyes of 22 healthy age- and sex-matched subjects forming control group HC. With color Doppler imaging we measured the peak systolic velocity (PSV, cm/s) and end-diastolic velocity (EDV, cm/s) of blood flow in the OA, CRA and PCA. The resistance index of each vessel was then calculated. Statistical analysis comparing the results of groups NPDR, SNPDR/PDR and HC was carried out. Statistical significance was set at p < 0.05. Results: There was a statistically significant increase in PSV in the OA in group SNPDR/PDR compared with group HC (35.71 ± 6.90 vs. 31.45 ± 4.32 cm/s; mean ± SD). There was a statistically significant decrease in PSV in the CRA in group NPDR compared with group HC (8.50 ± 1.62 vs. 10.61 ± 1.75 cm/s; mean ± SD) and in group SNPDR/PDR compared with group HC (7.34 ± 1.78 vs. 10.61 ± 1.75 cm/s; mean ± SD), also there was a statistically significant decrease in EDV in group SNPDR/PDR compared with group HC (2.05 ± 0.53 vs. 3.00 ± 0.81 cm/s; mean ± SD). A statistically significant decrease in EDV in the PCA in group SNPDR/PDR compared with group HC (2.95 ± 1.04 vs. 3.95 ± 0.98 cm/s; mean ± SD) was found, also there was a statistically significant increase in the resistance index in group SNPDR/PDR compared with group NPDR (0.72 ± 0.05 vs. 0.67 ± 0.07; mean ± SD) and in group SNPDR/PDR compared with group HC (0.72 ± 0.05 vs. 0.67 ± 0.05; mean ± SD). Conclusions: In this investigation, color Doppler imaging was used to determine significant changes of blood flow velocity in the OA, CRA and PCA in DR compared with healthy control subjects and the changes of blood flow velocity become further significant considering the progression of DR. This points to the presence of circulatory changes in the OA, CRA and PCA in diabetic patients with DR.