bluuebunny/crossref_metadata_2025 huggingface dataset:
Teaching Values in Everything We Do: The Nativity Experience
Authors: Grumhaus Daly Jennifer
Published: March 2007

Nativity Prep, a small, inner-city Roman Catholic middle Level school, can hardly be held up as a prototype for public secondary schools. But the students of this unusual school can teach all of us some lessons about love and caring and meeting expectations.
Designing an Effective In-School Suspension Program To Change Student Behavior
Authors: Sheets John
Published: March 2007

The most important goal of any discipline program should be to change unwanted student behavior. In-school suspension programs can accom plish this objective, but only if the program is appropriately designed and maintained to be an effective part of the school's total discipline philosophy.
Putting Teachers at the Center of Reform: Learning Schools and Professional Communities
Authors: Louis Karen Seashore , Kruse Sharon , Raywid Mary Anne
Published: March 2007

When schools are seen as learning organizations and professional com munities, attention is focused on teachers' work as a key instrument of reform. By emphasizing needed changes in the culture of schools and the daily practice of professionals, the reform movement can concen trate on the heart of the school—the teaching and learning process.
Family and Consumer Sciences in The 21st Century
Authors: Bowers Jan
Published: March 2007

Family and consumer sciences education empowers individuals and families across the life span to manage the challenges of living and working in a diverse global society. Its unique focus is on families, work, and their interrelationships.
Recent Directions in Music Education: Advocacy, Reform, And Research
Authors: Mahlmann John J.
Published: March 2007

For the Music Educators National Conference, as for many professional education associations, the 1990s have been dominated by the con cerns of advocacy, reform and standards, and new research.
The Future of Art Education
Authors: Hatfield Thomas A.
Published: March 2007

The goal of all elementary and secondary education in the arts, no mat ter what the career direction of the student, should be the develop ment of basic literacy in dance, music, theater, and the visual arts.
Business Education: A Discipline With a Proud Heritage Looks To the Future
Authors: Treichel Janet M.
Published: March 2007

For millions of students, business education courses offer life-chang ing knowledge and skills and hope for a better life. The curriculum also prepares students for college programs in business and related areas.
A Fresh Look at the NCTM Standards
Authors: Rosen Linda P. , Esty Edward T.
Published: March 2007

The National Council of Teachers of Mathematics, which inaugurated the "standards" movement in U.S. schools with the publication of the Curriculum and Evaluation Standards for School Mathematics in 1989, is taking a fresh look at its standards—not only for curriculum but for teaching and assessment as well.
Religion in the Public Schools: What Does the First Amendment Allow?
Authors: Okun Susan J.
Published: March 2007

While the major cases involving religion in public schools were decid ed decades ago, disputes still arise over interpretations of the First Amendment's establishment clause. One current battleground is the high school graduation ceremony. Until the Supreme Court has an opportunity to revisit the issue, school administrators must stay informed and be sensitive to the issue of religion in the public schools.
Individuality vs. Conformity: The Issue Behind School Uniforms
Authors: Caruso Peter
Published: March 2007

When we consider whether or not to implement a school uniform pot- icy, we need to understand the validity of each proponent's arguments. Do school uniforms make a difference or not?
Breaking Ranks: Changing the Inservice Institution
Authors: Licklider Barbara L.
Published: March 2007

High school affects students for the rest of their lives, which means high school educators wield a powerful influence. Some old ways in U.S. high schools must change if our country's future is to be as bright as possible. If we are to equip practitioners to lead the changes, we must also break ranks with the institution of inservice training.
Upgrading High School Mathematics: A Look at Three Transition Courses
Authors: White Paula A. , Porter Andrew C. , Gamoran Adam , Smithson John
Published: March 2007

Lower lever mathematics courses often become a dead end for low- achieving students. Several new upgraded math courses, however, reflecting emerging standards in mathematics, are raising student achievement and improving students' chances of taking college preparatory math.
Restructuring Schools To Be Math Friendly to Females
Authors: Karp Karen , Shakeshaft Charol
Published: March 2007

Recent reports indicate that although girls enter school more math- ready than boys, many are outdistanced by mates in math achievement by the time they graduate. Why is this? What happens to girls as they go through school that puts them at a math disadvantage? How can we change schools so that the lifelong impact of mathematics coursework can work in girls' favor?
The Instructional Coach: A New Ro In Instructional Improvement
Authors: Makibbin Shirley S. , Sprague Marsha M.
Published: March 2007

Ask any good teacher how he or she learned to be one, and the response is predictable: Someone helped the novice or fledgling teacher learn the "tricks of the trade." How can these experiences be translated into common practice? How can all teachers improve through the use of truly helpful interactions?
Self-Assessment and Reflection: Tools for Promoting Teacher Changes Toward Learner-Centered Practices
Authors: McCombs Barbara L.
Published: March 2007

Teachers need self-assessment and reflection tools to help them assess fundamental beliefs and assumptions about learning, learners, and teaching, as well as differences between their perceptions of practice and those held by students in their classroom. A process of reflection will help to identify the personal characteristics and practices that must change to improve motivation and achievement for each student.
Using the Socratic Method in Secondary Teaching
Authors: Schoeman Stephen
Published: March 2007

There is a place in secondary teaching for the traditional lecture and there is a place for the Socratic Method. Students learn from questions and not only from answers. They learn from being asked to justify their positions, to support their arguments with logic and with evidence.
Learning Centered Schools Using a Problem-Based Approach
Authors: Seifert Edward H. , Simmons David
Published: March 2007

It can be difficult to initiate and implement educational reform, espe cially instructional reform, in a traditional high school. Many obstacles must be overcome to achieve success: the departmentalization of the curriculum, beliefs about student ability, and beliefs about content and preparation for further learning.
Success and the Four Block Schedule: Stakeholders Buy In!
Authors: Fitzpatrick James E. , Mowers Mary
Published: March 2007

As schools consider moving toward the four block schedule, many have difficulty obtaining the necessary support to make the switch. Certainty there are obstacles to overcome in soliciting support. Often overlooked is the decision-making process that must be in place when considering the four-block. A top-down mandate is sure to result in failure. Gaining support from all the major stakeholders is critical.
The School as a Learning Organization: Recommendations For School Improvement
Authors: DuFour Richard P.
Published: March 2007

Those who have a genuine interest in leading school improvement ini tiatives must recognize that schools will not produce students as con tinuous learners and effective collaborators without teachers who have these same characteristics. The work of school improvement is the chal lenging but essential work of building schools as learning organizations.
Using Deming's Continuous Improvement Model To Improve Reading
Authors: Weller L. David , Weller Sylvia J.
Published: March 2007

Ask any high school teacher to identify the biggest obstacle standing between students and their success in high school and the answer will more than likely be how well they read. High school teachers understand all too well that the ability to read well almost guarantees a student's mastery of subject matter, while poor reading ability dooms that student to failure.
Implementing State Mathematics Standards in Delaware, New Jersey, And the District of Columbia
Authors: Danin Susan T.
Published: March 2007

What has been happening in math classrooms in Delaware, the District of Columia, and New Jersey, where the last three years have been spent developing math standards and frameworks with broad-based input from state and local stakeholders and guidance from national standards efforts?
How Effective an Educational Tool Is Student Community Service?
Authors: Alt Martha Naomi
Published: March 2007

Despite the popular appeal among the public, educators, parents, and even students for community service, there is surprisingly little firm evidence that students who engage in service learn more, develop in different ways, or learn different skills than those who do not. What are the implications for policy, further research, and school practice?
Quality Learning Organizations And Continuous Improvement: Implementing the Concept
Authors: Weller L. David , Weller Sylvia J.
Published: March 2007

Continuous improvement calls for a shift in perspective on the part of administrators and staff members. How does a staff actually implement the concept of continuous improvement in order to turn the school into a learning organization? What would such concepts look like in actual practice in the school setting?
Billiards in the Classroom: Learning Physics with Microworlds
Authors: Bertz Michael D.
Published: March 2007

Using a computer simulation environment that allows students to experiment and play helps them to build personal understanding of physics concepts that might otherwise be difficult to grasp. When used in conjunction with meaningful class activities, such an environment can foster active student learning, critical thinking, and collaboration.
Is Your Successor in Your Schoolhouse? Finding Principal Candidates
Authors: Barker Sandra L.
Published: March 2007

Look around at your fellow principals and assistant principals. What are their personal career plans? What are your plans? Were you to move on next year, would you be Leaving your school in capable hands? Where will schools and districts find new principals?
A Vision for Block Scheduling: Where Are We Now? Where Are We Going?
Authors: Shortt Thomas L. , Thayer Yvonne V.
Published: March 2007

A different use of time in classrooms can help students pursue topics in depth, learning more while developing the skills of the 21st century. A different use of time in schools offers the flexibility needed to design alternatives that serve student and teacher needs.
Initiating a Program in Social and Emotional Education
Authors: Pasi Raymond J.
Published: March 2007

School programs in social and emotional education seek to increase student self-awareness; enhance student skills in dealing with their emotions and interpersonal relationships; and improve student social decision-making abilities. Helping young people in these areas helps them in academics and in life, as well as enhancing the overall learning climate of the school.
Developing an information business - the HERTIS experience
Authors: Abell Angela
Published: March 2007

Analyses the development of HERTIS Information and Research for Industry from a subsidised techni cally biased service in the 1950s, to its present position as a self-funding information service for business and industry. Outlines the commercial background to a range of new services, and draws lessons for other infor mation service providers
Kinematic Design of Serial Link Manipulators From Task Specifications
Authors: Paredis Christiaan J. J. , Khosla Pradeep K.
Published: March 2007

The Reconfigurable Modular Manipulator System (RMMS) consists of modular links and joints that can be assembled into many manipulator configurations. This capability allows the RMMS to be rapidly reconfigured to custom tailor it to specific tasks. An important issue related to the RMMS is the determination of the optimal manipulator configuration for a specific task. This article addresses the problem of mapping kinematic task specifications into a kinematic manipulator configuration. For the design of two-degrees-of-freedom (2- DOF) planar manipulators, an analytical solution is derived. Because analytical solutions become impractical for problems with more than two design parameters, we have also developed a numerical approach for the design of 6-DOF manipulators. The numerical procedure determines the Denavit-Hartenberg (D-H) parameters of a nonredundant manipulator with joint limits that can reach a set of specified positions/orientations in an environment that may include parallelepiped-shaped obstacles. Finally, this approach is demonstrated with a three- dimensional example for a 6-DOF manipulator
Air-stable P-Chiral Bidentate Phosphine Ligand with (1-Adamantyl)methylphosphino Group
Authors: Imamoto Tsuneo , Kumada Atsushi , Yoshida Kazuhiro
Published: March 2007

Air-stable diphosphine ligand, (R,R)-2,3-bis((1-adamantyl)methylphosphino)quinoxaline, was prepared by the reaction of enantiomerically pure (S)-(1-adamantyl)methylphosphine–borane with 2,3-dichloroquinoxaline. The ligand exhibited excellent enantioselectivities in Rh-catalyzed asymmetric hydrogenation and Pd-catalyzed asymmetric ring-opening reaction.
Photodimerization Mechanism of Bis(3,4,5-trifluorobenzyl) (E,E)-Muconate in a Columnar Assembly in the Crystalline State
Authors: Mori Yutaka , Matsumoto Akikazu
Published: March 2007

We have revealed the photoreaction mechanism for the single-crystal-to-single-crystal transformation of bis(3,4,5-trifluorobenzyl) (E,E)-muconate (1) to the corresponding dimer. The [2 + 2] photodimerization randomly occurred in the columnar assembly of monomer molecules in the crystals of 1, followed by the formation of a trimer. The photoreaction was directly monitored by an X-ray single crystal structure analysis as well as the product analysis by NMR and MS spectroscopies.
Simulation Allocation for Determining the Best Design in the Presence of Correlated Sampling
Authors: Fu Michael C. , Hu Jian-Qiang , Chen Chun-Hung , Xiong Xiaoping
Published: March 2007

We consider the problem of efficiently allocating simulation replications in order to maximize the probability of selecting the best design under the scenario in which system performances are sampled in the presence of correlation. In the case of two designs, we are able to derive the optimal allocation exactly, and find that in the presence of positive correlation, unless the variance of one design is significantly larger than that of the other, the number of simulation replications should be identical. In extending to a general number of competing designs, an approximation for the asymptotically optimal allocation is obtained. The approximation coincides with the independent case derived previously in the limit as the correlation vanishes and also agrees with the two-design exact solution. Furthermore, the allocations prescribed by the results seem to match intuition, in terms of the relationship to correlations and relative variances between designs, again suggesting that equal allocation is optimal for sufficiently high positive correlation. An allocation algorithm based on the approximation is proposed and tested on several numerical examples.
A Compressed-Annealing Heuristic for the Traveling Salesman Problem with Time Windows
Authors: Ohlmann Jeffrey W. , Thomas Barrett W.
Published: March 2007

This paper describes a variant of simulated annealing incorporating a variable penalty method to solve the traveling-salesman problem with time windows (TSPTW). Augmenting temperature from traditional simulated annealing with the concept of pressure (analogous to the value of the penalty multiplier), compressed annealing relaxes the time-window constraints by integrating a penalty method within a stochastic search procedure. Computational results validate the value of a variable-penalty method versus a static-penalty approach. Compressed annealing compares favorably with benchmark results in the literature, obtaining best known results for numerous instances.
Quantifying Human Health Risks from Animal Antimicrobials
Authors: Cox Louis Anthony (Tony) , Popken Douglas A. , Carnevale Richard
Published: March 2007

In 1969, the Joint Committee on the Use of Antibiotics in Animal Husbandry and Veterinary Medicine in the United Kingdom warned that uncontrolled use of similar antimicrobials in humans and food animals might promote the emergence of resistant strains of foodborne bacteria that could endanger human health and compromise the effectiveness of antimicrobial therapies in human patients (Swann 1969). The Animal Health Institute (AHI) and its member companies collaborated with Cox Associates, an operations research consulting company, to develop and apply new, practical, quantitative risk assessment (QRA) modeling methods to assess the previously impossible-to-quantify risks (and benefits) to human health from continued use of animal antimicrobials. We came to some surprising conclusions that were robust to many uncertainties. Among these were that antimicrobials that benefit animal health may benefit human health, while regulatory interventions that seek to reduce antimicrobial resistance in animals may unintentionally increase illness rates (and hence antimicrobial use and resistance rates) in humans. These new QRA models and methods enable industry and regulatory decision makers to quantify and compare the probable human health consequences of alternative animal antimicrobial use plans and to design more effective approaches to protect human and animal health.
Coupons Versus Rebates
Authors: Lu Qiang , Moorthy Sridhar
Published: March 2007

This paper examines a key difference between two promotional vehicles, coupons and rebates. Whereas coupons offer deals up front, with the purchase of the product, rebates can be redeemed only after purchase. When consumers experience uncertain redemption costs, this difference translates to a difference in when uncertainty is resolved. With coupons the uncertainty is resolved before purchase; with rebates the uncertainty is resolved after purchase. As a result, we show that rebates are more efficient in surplus extraction but coupons offer more finetuned control over whom to serve.

We identify the conditions under which each is optimal, and these conditions turn on the gap between “low” reservation price consumers’ valuations and their highest redemption costs. Rebates are optimal when this gap is large; coupons tend to be optimal otherwise. Risk aversity on the part of consumers reduces the attractiveness of rebates, as does the delay between rebate redemption and rebate payment, but the latter if and only if consumers are more impatient than the seller. These observations match up well with what we know about the use of these promotional vehicles in the real world.
Spiffed-Up Channels: The Role of Spiffs in Hierarchical Selling Organizations
Authors: Caldieraro Fabio , Coughlan Anne T.
Published: March 2007

We study a channel relationship in which manufacturer(s) use independent sales representatives (rep firms), which employ salespeople to do the actual selling. We show that commission-only payments by manufacturers to rep firms lead to suboptimal outcomes for the manufacturer relative to those obtained under a vertically integrated channel. From the manufacturer’s standpoint, these inefficiencies can be ameliorated through the use of sales incentives given to the rep firm’s salespeople directly by the manufacturer (called “spiffs”).

In a monopolistic environment, spiffs are shown to improve the manufacturer’s profits in the face of contractual restrictions on the channel members’ ability to set separate commission rates by product. For certain types of restrictions, spiffs may generate manufacturer outcomes close to the fully coordinated ones achieved under vertical integration even when compensating the rep firm through commission-only contracts.

In a competitive environment, spiffs are shown to be used by a powerful manufacturer that shares a rep firm’s sales efforts with the product of a weaker manufacturer (i.e., in the case of “common agency”). In this case, spiffs are used as a strategy to deter the weaker manufacturer from challenging the stronger manufacturer for the salesforce’s valuable selling effort.
When Do Price Thresholds Matter in Retail Categories?
Authors: Pauwels Koen , Srinivasan Shuba , Franses Philip Hans
Published: March 2007

Marketing literature has long recognized that brand price elasticity need not be monotonic and symmetric, but has yet to provide generalizable market-level insights on threshold-based price elasticity, asymmetric thresholds, and the sign and magnitude of elasticity transitions. This paper introduces smooth transition regression models to study threshold-based price elasticity of the top 4 brands across 20 fast-moving consumer good categories. Threshold-based price elasticity is found for 76% of all brands: 29% reflect historical benchmark prices, 16% reflect competitive benchmark prices, and 31% reflect both types of benchmarks. The authors demonstrate asymmetry for gains versus losses on three levels: the threshold size and the sign and the magnitude of the elasticity difference. Interestingly, they observe latitude of acceptance for gains compared to the historical benchmark, but saturation effects in most other cases. Moreover, category characteristics influence the extent and the nature of threshold-based price elasticity, while individual brand characteristics impact the size of the price thresholds. From a managerial perspective, the paper illustrates the sales, revenue, and margin implications for price changes typically observed in consumer markets.
Editorial—Does Good Marketing Cause Bad Unemployment?
Authors: Shugan Steven M.
Published: March 2007

Questionable methods for increasing nominal wages reduce real wages (i.e., buying power) by creating inflation, shortages, lower quality, and long-term unemployment. To increase real wages (i.e., the ability to buy more), economic principles prescribe increasing productivity (i.e., greater output from less input). In contrast, marketing principles prescribes increasing the value of output (i.e., greater customer benefits) through innovation. Beyond increasing real wages, innovation spawns new occupations better matching individuals with skills and providing greater nonmonetary benefits (i.e., job satisfaction). Unfortunately, threatened entrenched incumbents often solicit protectionist legislation claiming negative externalities (e.g., short-term unemployment, lower wages, and burdens on society). Innovation does require labor to move from inferior to superior organizations (i.e., unemployment). However, protectionism only delays and dramatically aggravates the inevitable trauma associated with progress, as worker skills, firm practices, and buyer welfare fall further behind. Recent attacks demonizing Wal-Mart (e.g., the dubious Vlasic pickle claim) epitomize this situation—they are archaic vanilla protectionism, menacing both imperiled consumers and every consumer-driven business.
Transgenic mouse brains for the evaluation and quality control of BSE tests
Authors: Philipp Wolfgang J. , Groth Darlene , Giles Kurt , Vodrazka Pavel , Schimmel Heinz , Feyssaguet Muriel , Toomik Reet , Schacher Pascal , Osman Awad A. , Lachmann Ingolf , Wear Angus , Arsac Jean-Noel , Prusiner Stanley B.
Published: March 2007

Rapid BSE tests are widely used diagnostics in veterinary medicine and more than 11 million tests are applied worldwide. The evaluation of new rapid BSE tests and the quality assurance of approved BSE tests pose a challenge owing to the natural scarcity of BSE-infected bovine brainstems and regional variations in prion titer. Transgenic mice expressing bovine prion protein (Tg4092) offer an alternative approach to these problems. To determine whether BSE-infected Tg4092 mouse brains could serve as a general standard for rapid BSE tests, we inoculated Tg4092 mice intracerebrally with BSE prions, harvested brains at defined time points post-infection and analyzed cerebral hemispheres with several approved rapid BSE tests. The results show that de novo formation of the disease-causing prion protein isoform, PrPSc, can be monitored during the course of infection. We demonstrate that BSE-infected Tg4092 mouse brains provide a renewable and controllable source of reference samples and suggest that such samples can generally be used for the evaluation and quality control of rapid BSE tests.
Histone deacetylase inhibition and progesterone act synergistically to stimulate baboon glycodelin gene expression
Authors: Jaffe Randal C , Ferguson-Gottschall Susan D , Gao Weihua , Beam Craig , Fazleabas Asgerally T
Published: March 2007

During the late luteal phase of the menstrual cycle and early pregnancy, the major secretory product of the uterine glandular epithelial cells in humans and non-human primates is glycodelin. Previous studies using Ishikawa cells, a human endometrial cell line, have shown that a chimeric plasmid containing the baboon glycodelin promoter responds to progestins but the response is modest compared with the induction of glycodelin seen in vivo and in gene array analysis. A recent report indicating that the histone deacetylase inhibitor trichostatin A (TSA) promoted glycodelin expression prompted us to examine its mechanism of action. In Ishikawa cells transfected with the baboon glycodelin promoter, TSA and the synthetic progestin medroxyprogesterone acetate both stimulated expression of the reporter and the combined treatment produced a synergistic effect. The effect of TSA and progestin was absent when the same promoter constructs were transfected into COS-1 cells, a kidney cell line, and a TSA effect but no progestin effect was observed in T47D cells, a mammary cell line. Through deletion analysis, the TSA action was localized to the −67/−52 region of the baboon glycodelin promoter, a region which contains the proximal Sp1 site. Deletions of this same region had no effect on progestin responsiveness. Our findings indicate that at least two regions of the glycodelin promoter are important for the normal induction of glycodelin expression. Non-target cells may lack factors which act on the response elements resulting in the restriction of expression to the appropriate target tissue.
Chemokines as modulators of neuroendocrine functions
Authors: Rostene William , Buckingham Julia C
Published: March 2007

Chemokines are small secreted proteins with chemoattractant properties for immune cells. Besides their role in the immune system, chemokines and their receptors may play important roles in the central nervous system. Neurodegenerative disorders that involve neuroinflammation such as multiple sclerosis, stroke, Alzheimer’s disease, Parkinson’s disease and HIV-associated dementia are commonly associated with local upregulation and release of chemokines. However, recent work has established that certain chemokines, constitutively expressed in the brain, exert functions in the brain that are distinct from inflammation. These chemokines regulate neuronal migration during brain development, modulate neuronal activity and play a role in various neurodegenerative diseases, pain and more recently in neuroendocrine functions. All these novel aspects, mainly focused on the chemokine stromal cell-derived factor-1/CXCL12 and its receptor CXCR4, were presented by pioneers in the field during the symposium held at the sixth International Congress of Neuroendocrinology in Pittsburgh, Pennsylvania, USA in June 2006.
Role of cAMP in upregulation of insulin secretion during the adaptation of islets of Langerhans to pregnancy.
Authors: Weinhaus A J , Bhagroo N V , Brelje T C , Sorenson R L
Published: March 2007

Islets undergo a number of upregulatory changes to meet the increased demand for insulin during pregnancy, including an increase in glucose-stimulated insulin secretion with a reduction in the stimulation threshold. Treatment with the lactogenic hormone prolactin (PRL) in vitro has been shown to induce changes in islets similar to those observed during pregnancy. We examined cAMP production in islets treated with PRL to determine if changes in cAMP are involved in the upregulation of insulin secretion. Insulin secretion and cAMP concentrations were measured from islets in response to a suprathreshold (6.8 mmol/l) or high (16.8 mmol/l) glucose concentration in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine. Insulin secretion increased by 2.1-, 5.0-, and 5.9-fold at the suprathreshold glucose concentration and by 1.6-, 2.3-, and 2.9-fold at the higher glucose concentration after 1, 3, and 5 days of PRL treatment, respectively. After a similar pattern, cAMP metabolism increased by 1.2-, 1.6-, and 2.1-fold at the suprathreshold glucose concentration and by 1.2-, 1.7-, and 2.2-fold at the high glucose concentration after 1, 3, and 5 days of PRL treatment, respectively. The similar increases in insulin secretion and cAMP concentration suggest that changes in cAMP metabolism are involved in lactogen-induced upregulation of insulin secretion. To gain additional insight into the role of cAMP in the upregulation of islet function after lactogen treatment, we examined the relationship between changes in cAMP concentration and insulin secretion. Under all conditions (differing glucose concentrations and time periods), the increase in insulin release was directly proportional to the increase in cAMP. Thus increased glucose-stimulated insulin secretion from lactogen-treated islets could be accounted for by increased generation of cAMP and did not appear to require any further specific changes in intracellular processes mediated by cAMP. Because the PRL receptor is not directly involved in cAMP metabolism, the lactogen-induced increase in cAMP was most likely due to the increase in glucose metabolism that we have previously demonstrated in PRL-treated islets and in islets during pregnancy.
Trp64Arg mutation of beta3-adrenoceptor gene deteriorates lipolysis induced by beta3-adrenoceptor agonist in human omental adipocytes.
Authors: Umekawa T , Yoshida T , Sakane N , Kogure A , Kondo M , Honjyo H
Published: March 2007

The recently described variant of the human beta3-adrenergic receptor (AR) gene located mainly in visceral adipocytes is associated with earlier onset of NIDDM, abdominal obesity, insulin resistance, and an increased capacity to gain weight. We investigated whether lipolysis in human omental adipocytes induced by a potent and selective human beta3-AR agonist (L-755,507) was affected by the Trp64Arg mutation of the beta3-adrenoceptor, using 18 omental fat samples obtained during total hysterectomy. The Trp64Arg mutation was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Arg64 homozygous (n = 4) had a lower median effective concentration (EC50) and lower responsiveness compared with wild-type (n = 8) (EC50: -6.55 +/- 0.21 vs. -7.53 +/- 0.35 log mol/l, P = 0.007; responsiveness: 3.48 +/- 0.32 vs. 5.76 +/- 0.36 micromol x 10(5) cells(-1) x 90 min(-1), P = 0.014, respectively), although there was no difference in lipolysis induced by isoproterenol or CGP12177. Trp64Arg heterozygous (n = 6) also had a significantly lower EC50 and lower responsiveness (EC50: -6.18 +/- 0.09 log mol/l; responsiveness: 4.17 +/- 0.33 micromol x 10(5) cells(-1) x 90 min(-1)). We concluded that the Trp64Arg mutation of the beta3-AR gene is associated with lower lipolytic activities.
No evidence for association between IDDMK(1,2)22, a novel isolated retrovirus, and IDDM.
Authors: Jaeckel E , Heringlake S , Berger D , Brabant G , Hunsmann G , Manns M P
Published: March 2007

In the past, endogenous retroviral sequences have been isolated from patients suffering from different kinds of autoimmune diseases. Recently, a full length retroviral genome, termed IDDMK(1,2)22, was isolated from patients with new-onset IDDM. This genome contains a major histocompatibility complex II-dependent superantigen within its envelope gene. The viral sequence was found in ten patients with new-onset IDDM, but not in age-matched control subjects (Conrad et al. [9]). We searched for the presence of this viral genome by nested reverse transcription-polymerase chain reaction (RT-PCR) in a cohort of six patients with new-onset IDDM and six control subjects of the same age. We found all samples to be positive without any differences between patients and control subjects. The same results were obtained with supernatants of activated peripheral blood mononuclear cells. We performed isopycnic ultracentrifugation in sucrose density gradients on all samples and were unable to detect particles of the new virus in any of our samples. However, positive signals were obtained from all pellet fractions. RNase, DNase treatment and nested PCRs without reverse transcription showed that the positive signals were probably derived from intracellular RNA and DNA. In summary, no correlation between a positive nested PCR signal for IDDMK(1,2)22 and diabetes was found indicating that the new sequence represents just an additional member of the human endogenous retrovirus (HERV) family with lack of an exogenous counterpart.
Alpha-lipoic acid: effect on glucose uptake, sorbitol pathway, and energy metabolism in experimental diabetic neuropathy.
Authors: Kishi Y , Schmelzer J D , Yao J K , Zollman P J , Nickander K K , Tritschler H J , Low P A
Published: March 2007

The peripheral nerve of experimental diabetic neuropathy (EDN) is reported to be ischemic and hypoxic, with an increased dependence on anaerobic metabolism, requiring increased energy substrate stores. When glucose stores become reduced, fiber degeneration has been reported. We evaluated glucose uptake, nerve energy metabolism, the polyol pathway, and protein kinase C (PKC) activity in EDN induced by streptozotocin. Control and diabetic rats received lipoic acid (0, 10, 25, 50, 100 mg/kg). Duration of diabetes was 1 month, and alpha-lipoic acid was administered intraperitoneally 5 times per week for the final week of the experiment. Nerve glucose uptake was reduced to 60, s 37, and 30% of control values in the sciatic nerve, L5 dorsal root ganglion, and superior cervical ganglion (SCG), respectively, in rats with EDN. Alpha-lipoic acid supplementation had no effect on glucose uptake in normal nerves at any dose, but reversed the deficit in EDN, with a threshold between 10 and 25 mg/kg. Endoneurial glucose, fructose, sorbitol, and myo-inositol were measured in sciatic nerve. Alpha-lipoic acid had no significant effect on either energy metabolism or polyol pathway of normal nerves. In EDN, endoneurial glucose, fructose, and sorbitol were significantly increased, while myo-inositol was significantly reduced. Alpha-lipoic acid had a biphasic effect: it dose-dependently increased fructose, glucose, and sorbitol, peaking at 25 mg/kg, and then fell beyond that dose, and it dose-dependently increased myo-inositol. Sciatic nerve cytosolic PKC was increased in EDN. ATP, creatine phosphate, and lactate were measured in sciatic nerve and SCG. Alpha-lipoic acid prevented the reduction in SCG creatine phosphate. We conclude that glucose uptake is reduced in EDN and that this deficit is dose-dependently reversed by alpha-lipoic acid, a change associated with an improvement in peripheral nerve function.
Modifications induced by LDL from type 1 diabetic patients on endothelial cells obtained from human umbilical vein.
Authors: Rabini R A , Cester N , Staffolani R , Salvolini E , Moretti N , Vignini A , Fumelli D , Mazzanti L
Published: March 2007

The aim of the present work was to analyze the effect of LDL obtained from type 1 diabetic patients in good metabolic control on human umbilical vein endothelial cells (HUVECs) after a short incubation period to detect possible atherogenic modifications of endothelial properties. Cultured HUVECs were incubated for 3 h with culture medium alone (control HUVEC), with native LDL from 12 healthy men (control LDL), or with native LDL from 12 type 1 diabetic men (type 1 LDL) (100 pg/ml). After the incubation, the following parameters were evaluated: nitric oxide synthase (NOS) activity, cytoplasmic Ca2+ levels, Na+-K+-ATPase activity, plasma membrane fluidity determined by means of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), and plasma membrane conjugated diene (CD) content. The same experiments were repeated after bradykinin stimulation or in the presence of the antioxidant butylated hydroxytoluene (BHT), and nitric oxide (NO) production in intact HUVECs was also evaluated. HUVECs incubated with control LDL in comparison with control HUVECs showed a decreased fluidity of the membrane surface evaluated by TMA-DPH and a higher CD content. These alterations were prevented by the presence of BHT. HUVECs incubated with type 1 LDL in comparison with both control HUVECs and cells incubated with control LDL showed 1) increased NOS and Na+-K+-ATPase activity, cytoplasmic Ca2+ levels, and CD content, and 2) decreased fluidity of the membrane surface evaluated by TMA-DPH. These modifications were blunted--but not abolished--by the presence of BHT. After bradykinin stimulation either in the absence or in the presence of BHT, both cytoplasmic Ca2+ levels and NO production were increased in control HUVECs and in HUVECs incubated with control LDL, while a reduced response was observed in HUVECs incubated with type 1 LDL. The alterations observed in the endothelial function after the cell-LDL interaction might play a central role in the atherogenic process in diabetes.
Hemodynamic basis for the acute cardiac effects of troglitazone in isolated perfused rat hearts.
Authors: Shimoyama M , Ogino K , Tanaka Y , Ikeda T , Hisatome I
Published: March 2007

Troglitazone is a thiazolidinedione used for the treatment of NIDDM and potentially for other insulin-resistant disease states. Troglitazone has recently been shown to increase cardiac output and stroke volume in human subjects. These actions are thought to be mediated by the reduction of peripheral resistance, but a potential direct effect on cardiac function has not been studied. Therefore, we investigated the direct cardiac hemodynamic effects of troglitazone in isolated perfused rat hearts. Five groups of hearts were studied. Hearts were tested under isovolumetric contraction with a constant coronary flow, and troglitazone (0.2, 0.5, and 1.0 micromol) was administered by bolus injection. Peak isovolumetric left ventricular pressure (LVPmax), peak rate of rise of LVP (dP/dt(max)), and peak rate of fall of LVP (dP/dt(min)) were significantly increased 1 min after troglitazone administration in a dose-dependent manner, while the heart rate (HR) and coronary perfusion pressure (CPP) were significantly decreased (P < 0.05). HR was then fixed by pacing and/or CPP was fixed with nitroprusside to eliminate any effect of the two variables on the action of troglitazone. With constant HR and/or constant CPP, the effect of troglitazone on LVPmax, dP/dt(max), and dP/dt(min) was still unchanged. In addition, the positive inotropic, positive lusitropic, and negative chronotropic actions of troglitazone were not influenced even when hearts were pretreated with prazosin, propranolol, or nifedipine. In conclusion, troglitazone has direct positive inotropic, positive lusitropic, negative chronotropic, and coronary artery dilating effects. The inotropic and chronotropic actions of troglitazone are not mediated via adrenergic receptors or calcium channels. These findings have important clinical implications for diabetic patients with congestive heart failure.
Hepatic insulin resistance and defects in substrate utilization in cystic fibrosis.
Authors: Hardin D S , LeBlanc A , Para L , Seilheimer D K
Published: March 2007

Patients with cystic fibrosis (CF)-related diabetes (CFRD) have clinical features of both type 1 and type 2 diabetes. Past studies have documented peripheral insulin resistance in CF, and some studies have noted high hepatic glucose production (HGP) in CF patients. We hypothesized that patients with CF, similar to patients with type 2 diabetes, have hepatic insulin resistance. Cystic fibrosis is a catabolic condition, yet the etiology of catabolism is poorly understood. De novo lipogenesis is energy wasteful and precludes ketogenesis. Patients with CFRD rarely develop ketogenesis, despite insulin deficiency. We speculated that CF patients have de novo lipogenesis, and therefore evaluated substrate utilization in CF. Using [6,6-2H2]glucose and a three-step hyperinsulinemic-euglycemic clamp, we measured HGP in 29 adult CF subjects and 18 control volunteers. Using indirect calorimetry, we measured lipid oxidation, oxidative glucose metabolism, and resting energy expenditure at baseline and at high levels of insulin. All subjects were characterized by oral glucose tolerance testing (OGTT) and National Diabetes Data Group criteria. The CF subjects had increased HGP when compared with control subjects (CF, 3.5+/-0.6; control, 2.5+/-0.5 mg x kg(-1) x h(-1); P = 0.002). Baseline HGP correlated with glucose levels obtained 2 h after a glucose load given for OGTT (r = 0.69, P = 0.001). Suppression of HGP by insulin was significantly less in all CF subgroups than in control subjects at peripheral insulin levels of 16 and 29 microU/ml. At peripheral insulin levels of 100 microU/ml and 198 microU/ml, there was no difference in insulin suppression of HGP between CF and control subjects. At baseline, there was no significant difference between control and CF subjects for glucose or lipid oxidation. During maximum insulin stimulation, there was a greater tendency for nonoxidative glucose metabolism in all CF subjects. The CF subjects with abnormal glucose tolerance also had de novo lipogenesis. Our results indicate that CF patients have several defects in substrate utilization, including de novo lipogenesis. Furthermore, these results suggest that high hepatic glucose production and hepatic insulin resistance contribute to the high incidence of abnormal glucose tolerance in CF.
Onset of type 1 diabetes: a dynamical instability.
Authors: Freiesleben De Blasio B , Bak P , Pociot F , Karlsen A E , Nerup J
Published: March 2007

Type 1 diabetes is a disease characterized by progressive loss of beta-cell function due to an autoimmune reaction affecting the islets of Langerhans. It is now generally accepted that cytokines are implicated in the pathogenesis of autoimmune diseases. Animal studies have shown that interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma affect type 1 diabetes development profoundly. It has been suggested that beta-cells are destroyed by cytokine-induced free radical formation before cytotoxic T-helper (Th)-lymphocytes and/or autoantibody-mediated cytolysis. This hypothesis is known as the "Copenhagen model." We introduce a mathematical model encompassing the various processes within this framework. The model is expressed in rate equations describing the changes in numbers of beta-cells, macrophages, and Th-lymphocytes. Being concerned with the earliest events, we explore the conditions necessary to maintain self-sustained beta-cell elimination based on the feedback between immune cells and insulin-producing cells. The motivation for this type of analysis becomes clear when we consider the multifactorial and complicated nature of the disease. Indeed, recent research has provided detailed information about the different factors that contribute to the development of the disease, stressing the importance of incorporating these findings into a more general picture. A mathematical formalism allows for a more comprehensive description of the biological problem and can reveal nonintuitive properties of the dynamics. Despite the rather complicated structure of the equations, our main conclusion is simple: onset of type 1 diabetes is due to a collective, dynamical instability, rather than being caused by a single etiological factor.
Nitric oxide synthase inhibition reduces leg glucose uptake but not blood flow during dynamic exercise in humans.
Authors: Bradley S J , Kingwell B A , McConell G K
Published: March 2007

Nitric oxide (NO) appears to play a role in contraction-stimulated glucose uptake in isolated rodent skeletal muscle; however, no studies have examined this question in humans. Seven healthy men completed two 30-min bouts of supine cycling exercise at 60 +/- 2% peak pulmonary oxygen uptake (VO2 peak), separated by 90 min of rest. The NO synthase inhibitor N(G)-monomethyl-L-arginine ([L-NMMA]; total dose 5 mg/kg body weight) or saline (control) were administered via the femoral artery for the final 20 min of exercise in a randomized blinded crossover design. L-Arginine (5 mg/kg body weight) was co-infused during the final 5 min of each exercise bout. Leg blood flow (LBF) was measured by thermodilution in the femoral vein, and leg glucose uptake was calculated as the product of LBF and femoral arteriovenous (AV) glucose difference. L-NMMA infusion significantly (P < 0.05) reduced leg glucose uptake compared with control (48 +/- 12% lower at 15 min, mean +/- SE). The reduction in glucose uptake was due solely to a decrease in AV glucose difference, as there was no effect of L-NMMA infusion on LBF during exercise. Co-infusion of L-arginine restored glucose uptake during L-NMMA infusion to levels similar to control. These results indicate that NO production contributes substantially to exercise-mediated skeletal muscle glucose uptake in humans independent of skeletal muscle blood flow.
The perils of portliness: causes and consequences of visceral adiposity.
Authors: Montague C T , O'Rahilly S
Published: March 2007

Although an individual's total fat mass predicts morbidities such as coronary artery disease and diabetes, the anatomical distribution of adipose tissue is a strong and independent predictor of such adverse health outcomes. Thus, obese individuals with most of their fat stored in visceral adipose depots generally suffer greater adverse metabolic consequences than similarly overweight subjects with fat stored predominantly in subcutaneous sites. A fuller understanding of the biology of central obesity will require information regarding the genetic and environmental determinants of human fat topography and of the molecular mechanisms linking visceral adiposity to degenerative metabolic and vascular disease. Here we attempt to summarize the growing body of data relevant to these key areas and, in particular, to illustrate how recent advances in adipocyte biology are providing the basis for new pathophysiological insights.