bluuebunny/crossref_metadata_2025 huggingface dataset:
An Exploratory Study of Student Perceptions of Which Classroom Policies Are Fairest
Authors: Duplaga Edward A. , Astani Marzie
Published: January 2010

Fairness is a critical issue in the educational setting, and the research is unified in the view that professors need to be fair in setting course policies and procedures. However, many unanswered questions still remain as to which specific classroom policies and procedures students find fair or unfair. This study explores student perceptions of which course policies provide the fairest treatment for all students in a college class. In addition, we also investigate the presence of a relationship between students’ locus of control and their perceptions of the fairest course policies. Data were provided by 254 undergraduate students enrolled in sections of an introductory operations management course or an introductory management information systems course. As an initial, exploratory study in this specific area, eight common classroom policy situations were investigated. Although, not surprisingly, all students did not agree on which policy was the fairest for any given classroom situation, we were able to identify those policies considered fairest by the most students. The results can help professors develop course policies that improve students’ perceptions of fairness in the college classroom.
Effects of Transparency and At‐Stakeness on Students’ Perceptions of Their Ability to Work Collaboratively in Effective Classroom Teams: A Partial Test of the Jassawalla and Sashittal Model
Authors: Jassawalla Avan R. , Sashittal Hemant C. , Malshe Avinash
Published: January 2010

While teams are common in business school classrooms, scholars note that few instructors provide teamwork‐related instruction. The consequent negative experiences may explain the reported cynicism about teamwork among students. This article reports findings from a study that examined the link between a teaching strategy designed to help students function more effectively in teams and its impact on student perceptions of their ability to work collaboratively with others and on their perceptions of their team's effectiveness. The study found evidence to suggest that a teaching strategy designed to help students reach the multiple stages of team development such as high levels of at‐stakeness and transparency positively impacts their perceptions and that these stages effectively mediate the link between the strategy and key outcomes.
Why Is Performance on Multiple‐Choice Tests and Constructed‐Response Tests Not More Closely Related? Theory and an Empirical Test*
Authors: Kuechler William L. , Simkin Mark G.
Published: January 2010

Both professional certification and academic tests rely heavily on multiple‐choice questions, despite the widespread belief that alternate, constructed‐response questions are superior measures of a test taker's understanding of the underlying material. Empirically, the search for a link between these two assessment metrics has met with limited success, leading some researchers to conclude that the relationship is close and others to conclude that no relationship exists at all. The authors suggest that “knowledge level” may play a key role in explaining this disparity in findings. This article outlines the theory for such a concept, and investigates the possibility using 172 carefully constructed tests in several entry‐level programming classes. The article also discusses several caveats that suggest the usefulness of yet further research in the area.
A Reference Model for Sustainable E‐Learning Service Systems:Experiences with the Joint University/Teradata Consortium
Authors: Demirkan Haluk , Goul Michael , Gros Mary
Published: January 2010

Many e‐learning service systems fail. This is particularly true for those sponsored by joint industry/university consortia where substantial economic investments are required up‐front. This article provides an industry/university consortia reference model validated through experiences with the 8‐year‐old Teradata University Network. The reference model addresses basic and advanced sustainability capabilities that integrate partner, application, faculty, student, and e‐learning service system issues. Our validation of the reference model includes a mapping to the literature regarding recent advances in e‐learning service system infrastructures and supported capabilities. One outcome of that validation step is a comprehensive set of capability assessment questions to be used by consortia.
The “End Of History” 20 Years Later
Authors: FUKUYAMA FRANCIS
Published: January 2010

Twenty years after the fall of the Berlin Wall and the triumphant celebrations of the West, a new chapter of history has opened featuring the rising powers of Asia, led by China. Though embracing free markets, China has looked to its Confucian traditions instead of liberal democracy as the best route to good governance.

Will China manage to achieve high growth and a harmonious society through a strong state and long‐range planning that puts messy Western democracy and its short‐term mindset to shame? Or, in the end, will the weak rule of law and absence of political accountability in a one‐party state undermine its promise?

Francis Fukuyama and Kishore Mahbubani, the Singaporean thinker who has become the apostle of non‐Western modernity, debate these issues.

In this section we also republish a collective memoir by George H.W. Bush, Mikhail Gorbachev, Margaret Thatcher and François Mitterrand, recalling their fears and hopes two decades ago as they brought the Cold War to an end.
Financial Markets Must Not Return to “Bad Old Ways”
Authors: BARROSO JOSÉ MANUEL
Published: January 2010

Thanks to the draining effects of the Iraq war and the financial meltdown emanating from Wall Street, a powershift away from American dominance is taking place. Caught between a rising China and an America in relative decline, the new leadership in Japan is recalibrating its post‐World War II relationships. The G‐20 has usurped the role once played by the G‐8 as the governing committee of globalization. And the symbiotic coupling of “Chimerica”, born out of the credit bubble built up over the past two decades, is being put to the test.

In this section, the new prime minister of Japan, the president of the European Union, the president of Brazil and a leading economic historian assess these shifts.
The G‐2: Are America and China Headed for Divorce?
Authors: FERGUSON NIALL
Published: January 2010

Thanks to the draining effects of the Iraq war and the financial meltdown emanating from Wall Street, a powershift away from American dominance is taking place. Caught between a rising China and an America in relative decline, the new leadership in Japan is recalibrating its post‐World War II relationships. The G‐20 has usurped the role once played by the G‐8 as the governing committee of globalization. And the symbiotic coupling of “Chimerica”, born out of the credit bubble built up over the past two decades, is being put to the test.

In this section, the new prime minister of Japan, the president of the European Union, the president of Brazil and a leading economic historian assess these shifts.
Rebalancing the Global Economy: China Must Allow Currency to Rise, US Must Boost Savings
Authors: STRAUSS‐KAHN DOMINIQUE
Published: January 2010

Thanks to the draining effects of the Iraq war and the financial meltdown emanating from Wall Street, a powershift away from American dominance is taking place. Caught between a rising China and an America in relative decline, the new leadership in Japan is recalibrating its post‐World War II relationships. The G‐20 has usurped the role once played by the G‐8 as the governing committee of globalization. And the symbiotic coupling of “Chimerica”, born out of the credit bubble built up over the past two decades, is being put to the test.

In this section, the new prime minister of Japan, the president of the European Union, the president of Brazil and a leading economic historian assess these shifts.
Don't Sacrifice Democracy in Negotiations With Iran
Authors: EBADI SHIRIN
Published: January 2010

As the confrontation between the West and Iran over uranium enrichment comes to a head, the internal confrontation in Iran between the partisans of divine sovereignty, allied with the Revolutionary Guard, and popular sovereignty continues to simmer.

In this section, the first president of the Islamic Republic, a leading cleric of the opposition, the Iranian human rights activist and Nobel Laureate Shirin Ebadi and a former British intelligence agent ponder what lies ahead.
A Review of Vasomotor Responses of Arterioles on the Surface of the Mouse Brain: The Necessary Prelude to Studies Using Genetically Manipulated Mice
Authors: ROSENBLUM WILLIAM I.
Published: January 2010

Objective: To review the published data concerning the vasomotor responses of arterioles on the surface of the mouse brain. This information is essential to the planning of studies using genetically manipulated mice to investigate the control of cerebral vascular resistance.

Results: Cerebral vasomotor responses of mice have been reported using a wide variety of vasoactive agents. The responses are usually like those of other laboratory animals. Some agents are capable of elicting opposing dilating and constricting responses. The initial tone of the arteriole is one of several factors that can determine the direction of the response elicited by such agents. Endothelium‐dependent dilators and constrictors have been described. There are a variety of endothelium‐derived relaxing factors (EDRFs). Only one of these is synthesized by nitric oxide synthase (NOS). Antisense data suggests that both the endothelial and the neuronal isoforms of NOS may exist in the endothelial cells of these vessels. Several diseases can be modeled in mice and cerebrovascular responses studied. Studies of genetically modified mice suggest that the endothelial form of NOS contributes to microvascular events, which limit ischemic damage to brain parenchyma. However, during and following ischemia there may be loss of this NOS or inability to mobilize a storage form of the EDRF, which it produces.

Conclusions: Data available from studies of mice provide a good basis for planning further studies, examining cerebrovascular control mechanisms in health and disease, by workers now using genetically modified mice. The latter represent a powerful and increasingly popular tool for this purpose.
Differential Expression of Platelet‐Endothelial Cell Adhesion Molecule‐1 (PECAM‐1) in Murine Tissues
Authors: EPPIHIMER MICHAEL J. , RUSSELL JANICE , LANGLEY ROBERT , VALLIEN GINA , ANDERSON DONALD C. , GRANGER D. NEIL
Published: January 2010

Objective: To characterize and compare the expression of PECAM‐1 in unstimulated and tumor necrosis factor α‐ (TNF‐α)‐stimulated tissues of mice.

Methods: Binding and non‐binding monoclonal antibodies (mAb) were radio‐labeled and injected into wild‐type mice deficient of P‐selectin, CD18, or ICAM‐1. The relative accumulation of binding mAb (PECAM‐1 mAb) was determined in wild‐type mice following a 25 µg/kg i.p. injection of TNF‐α and in mutant mice under basal conditions.

Results: Under unstimulated conditions, PECAM‐1 was significantly expressed in all tissues examined, with no changes occurring after TNF‐α stimulation. An equivalence of PECAM‐1 expression was observed in unstimulated tissues among wild‐type mice and mice that are genetically deficient in either CD18, ICAM‐1, or P‐selectin. The level of PECAM‐1 expression in different vascular beds was highly correlated to published values of endothelial surface area. Normalization of previously published values of ICAM‐1, VCAM‐1, E‐ and P‐selectin expression relative to PECAM‐1 expression in the same tissues revealed a diminished organ‐to‐organ variability in expression of the different adhesion molecules. Estimates of adhesion molecule expression in lung and brain were most profoundly affected by normalization to PECAM‐1 expression.

Conclusions: These findings support the use of PECAM‐1 expression in regional vascular beds as an indicator of endothelial cell surface area.
An Absolute Requirement for P‐Selectin in Ischemia/Reperfusion‐Induced Leukocyte Recruitment in Cremaster Muscle
Authors: KANWAR SAMINA , SMITH C. WAYNE , KUBES PAUL
Published: January 2010

Objective: To systematically examine a role for P‐selectin in a model of striated muscle ischemia/reperfusion (I/R).

Methods: Ischemia was induced in the cremaster muscle of mice by occluding the main feeding arteriole for 30 minutes. Blood flow was then restored to allow for 60 minutes of reperfusion and leukocyte kinetics were assessed during the control period (before I/R) and at 5, 30, and 60 minutes of reperfusion. To study a role for P‐selectin in this model, three different approaches were used: Wildtype animals received fucoidin (10 mg/kg, iv), an anti‐P‐selectin antibody (RB40.34; 20 mg/animal, iv) at 25 minutes of ischemia, or I/R was induced in P‐selectin‐deficient mice.

Results: Ischemia/reperfusion induced a rapid and significant increase in leukocyte rolling, adhesion, and emigration in wild‐type mice. The I/R‐induced increase in leukocyte rolling was transient, inasmuch as it was reduced by approximately 50% at 30 minutes of reperfusion, and returned to control levels by 60 minutes. Both fucoidin and an anti‐P‐selectin antibody completely prevented the I/R‐induced increase in leukocyte rolling. The P‐selectin‐deficient animals exhibited absolutely no baseline leukocyte rolling, adhesion, or emigration. Furthermore, I/R did not induce any increase in leukocyte recruitment in the Pselectin‐deficient animals over the first 60 minutes of reperfusion.

Conclusion: The results from this study clearly illustrate that P‐selectin is absolutely critical in both baseline and I/R‐induced leukocyte infiltration in the murine‐striated muscle.
Effects of Environmental Stress on the Architecture and Permeability of the Rat Mesenteric Microvasculature
Authors: WILSON LISA M. , BALDWIN ANN L.
Published: January 2010

Objective: This study was performed to determine the effects of environmental stress on the leakage to albumin and architecture of microvessels in the rat mesentery.

Methods: One group of rats (Group A, n = 6) were examined immediately upon arrival at the animal care facility. Groups B (n = 24) and C (n = 32) were housed in rooms with high and low personnel activity, respectively, for up to 7 weeks. Group D (n =18) was housed in the high activity room for 2, 3, or 4 weeks followed by the low activity room.

Results: Rats in the low activity room for 3–4 weeks showed robust microvascular networks within 25% to 50% of the mesenteric windows (each window consisting of the tissue extending between two adjacent feeding arterioles in the mesentery), whereas rats in Group B only showed fragile vessels at the edges of the mesenteric windows within fat deposits. Groups A and C demonstrated little mesenteric fat and few fragile vessels, in contrast to group B. Group D showed increased mesenteric networks and decreased mesenteric fat as recovery progressed. The microvascular networks of 6 rats, randomly selected from Group C, showed few venular leaks following perfusion with fluorescein isothiocyanatelabeled bovine serum albumin (FITC‐BSA). Such leaks were abundant in the mesenteric microvasculature of 3 rats randomly selected from Group B.

Conclusions: This study demonstrates that environmentally induced stress alters the architecture and leakage to albumin of the rat mesenteric microvasculature, and emphasizes the importance of closely monitoring the environment of experimental animals.
A Mechanism of Oxygen Free Radical Production in the Dahl Hypertensive Rat
Authors: SWEI ALLEN , LACY FRED , DELANO FRANK A. , PARKS DALE A. , SCHMID‐SCHÖNBEIN GEERT W.
Published: January 2010

Objective: To determine if oxygen free radicals derived from xanthine oxidase are involved in the development of salt‐induced hypertension. Enhanced production of oxygen free radicals may play a role in hypertension by affecting vascular smooth muscle contraction and provide a mechanism for lesion formation.

Methods: Dahl salt‐sensitive (Dahl‐S) and salt‐resistant (Dahl‐R) rats were fed either a low‐salt, high‐salt or high‐salt + tungsten diet for 4 wk. In vivo production of superoxide (O2−) was detected by the reduction of a tetranitroblue tetrazolium (TNBT) dye in the rat mesentery, while plasma hydrogen peroxide (H2O2) production levels were determined using a modified electrochemical electrode technique.

Results: The tungsten diet lowered the blood pressure of Dahl‐S rats compared to high‐salt‐treated Dahl‐S rats, but had no effect on blood pressure in Dahl‐R rats. Light absorption of formazan deposits revealed that tungsten‐treated Dahl‐S rats had reduced TNBT staining along the endothelium of arterioles and venules compared to hypertensive, high‐salt‐treated Dahl‐S rats. In addition, tungsten‐treated Dahl‐S rats had a lower plasma H2O2 concentration compared to hypertensive, high‐salt‐treated Dahl‐S rats.

Conclusions: These findings indicate that xanthine oxidase‐derived oxygen free radicals are involved in the pathogenesis of salt‐induced hypertension.
Tissue Oxygenation Modifies Nitric Oxide Bioavailability
Authors: HEYMAN SAMUEL N. , GOLDFARB MARINA , DARMON DAVID , BREZIS MAYER
Published: January 2010

Objective: Because changes in blood oxygenation acutely alter vascular tone, we explored a possible modulation of nitric oxide‐induced vasodilation (nitrovasodilation) by oxygen.

Methods: We studied the effects of manipulation of tissue oxygenation on renal parenchymal nitric oxide (NO) with a selective NO electrode placed in the well‐oxygenated renal cortex or in the physiologically hypoxemic outer medulla.

Results: In the cortex, as expected, NO signals fell in response to the NO synthase (NOS) inhibitor L‐NAME. By contrast, in the outer medulla, NO signals paradoxically rose following NOS inhibition, known to intensify local hypoxia. Other manipulations that intensify outer medullary hypoxia (such as indomethacin or radiologic contrast media) increased local NO readings, while measures known to ameliorate outer medullary hypoxia (furosemide, L‐arginine, hypotension) reduced regional NO readings.

Conclusions: Oxygen appears to modulate NO bioavailability, in particular, in tissues with low ambient pO2, perhaps through enhanced binding to oxygenated hemoglobin. It is proposed that this phenomenon may participate in physiological microvascular regulation, with hypoxemia enhancing NO concentration, while hyperoxemia resulting in accelerated NO removal.
T‐Lymphocytes Contribute to Hepatic Leukostasis and Hypoxic Stress Induced by Gut Ischemia‐Reperfusion
Authors: HORIE YOSHINORI , WOLF ROBERT , CHERVENAK ROBERT P. , JENNINGS STEPHEN R. , GRANGER D. NEIL
Published: January 2010

Although neutrophils have been implicated in the hepatic injury elicited by gut ischemia/reperfusion (I/R), the contribution of other leukocyte populations to this injury process remains unclear. The objective of this study was to determine whether lymphocytes contribute to gut I/R‐induced microvascular dysfunction and inflammatory responses in the liver. Intravital videomicroscopy was used to monitor leukocyte recruitment, the number of nonperfused sinusoids and pyridine nucleotide (NADH) autofluorescence in livers of wild‐type, SCID, and interferon‐γ (IFN‐γ) knockout mice exposed to 15 min of gut ischemia and 1 h of reperfusion. In wild‐type mice, gut I/R elicited significant increases in the number of stationary leukocytes, nonperfused sinusoids, NADH autofluorescence (indicating hypoxia), and elevated plasma alanine aminotransferase (ALT) and TNF‐α levels. All of these responses were profoundly attenuated in SCID mice, while only some of the responses (in the midzonal region) were blunted in IFN‐γ knockout mice. Reconstitution (24 h before ischemia) of the circulating lymphocyte pool with T‐cell enriched splenocytes, but not T‐cell deficient (from nude mice), CD4+ T‐cell depleted splenocytes or splenocytes derived from IFN‐γ knockout mice, allowed the SCID mice to respond to gut I/R in a manner similar to wild‐type mice. Some of the responses were restored following reconstitution with CD8+ T‐cell depleted splenocytes. These findings implicate CD4+ Tlymphocytes and IFN‐γ in the hepatic microvascular dysfunction and inflammatory cell accumulation elicited by gut I/R.
In Vivo Assessment of Synovial Microcirculation and Leukocyte‐Endothelial Cell Interaction in Mouse Antigen‐Induced Arthritis
Authors: VEIHELMANN ANDREAS , HARRIS ANTHONY GUSTAVE , KROMBACH FRITZ , SCHÜTZE ELKE , REFIOR HANS JÜRGEN , MESSMER KONRAD
Published: January 2010

Objective: The microcirculation and leukocyte‐endothelial cell interaction in synovial tissue of an inflamed joint are known to play a crucial role in the pathogenesis of rheumatoid arthritis. The aim of this study was to characterize the in vivo changes in the microvasculature and in leukocyte‐endothelial cell interactions in the mouse synovial tissue using intravital fluorescence microscopy in three stages of antigen‐induced arthritis. The expression of E‐ and P‐selectin and ICAM‐1 were also studied using immunohistochemistry.

Methods: Antigen‐induced arthritis (AiA) was produced in Balb/c mice. The severity of arthritis at three different phases was quantified using a clinical and histological score. For the intravital fluorescence microscopy measurements, the patella tendon was partially resected for visualization of the intraarticular synovial tissue of the knee joint. The number of rolling and adherent leukocytes, functional capillary density (FCD) and RBC velocity were quantitatively measured in synovial microvessels. Expression of ICAM‐1, E‐ and P‐selectin was assessed by immunohistochemistry.

Results: There was a significant increase in the leukocyte rolling fraction in postcapillary venules in the acute phase of AiA (from 0.26 ± 0.05 in controls to 0.45 ± 0.04 8 d after AiA induction). The number of leukocytes adherent to the endothelium was significantly elevated in all phases of arthritis (from 121 ± 27 in controls to 376 ± 62 mm2 63 d after AiA‐induction). Functional capillary density was significantly enhanced in the acute (332 ± 15 cm/cm2) and intermediate phases (320 ± 15 cm/cm2) compared to control values (227 ± 15 cm/cm2). Arthritis resulted in a distinct increase in the expression of ICAM‐1 on the synovial endothelium in all phases of AiA. E‐ and P‐selectin expression were detected only in the acute phase.

Conclusion: Our model provides new insights into the microcirculatory changes which occur in the synovial tissue of an arthritic joint.
Quantitative Image Analysis of F‐Actin in Endothelial Cells
Authors: EHRINGER WILLIAM D. , YAMANY SAMEH , STEIER KELLY , FARAG ALY , ROISEN FREDERICK J. , DOZIER ALAN , MILLER FREDERICK N.
Published: January 2010

Objective: Filamentous actin (F‐actin) plays a central role in maintaining endothelial barrier function. Thrombin and histamine, two inflammatory mediators that increase endothelial permeability, can alter F‐actin production and distribution. In this study, we use a newly developed image analysis technique to show that these two inflammatory mediators differentially alter F‐actin structure.

Methods: Human umbilical vein endothelial cells were grown to confluence and treated with either histamine (1 µM), thrombin (1 µM) or the agonist's vehicle. The endothelium was stained with BODIPY‐phallodin, and digitized images were taken of the treated cells. The digitized images of individual human umbilical vein endothelial cells (HUVEC) were imported into a F‐actin image analysis program (FAAP) and converted to layers, each one‐pixel thick. The program then determined the mean gray level (which corresponded to the amount of F‐actin) in each layer starting from the outside of the cell (layer 1) and progressing in one pixel layer increments towards the center of the cell (layer 32).

Results: Both inflammatory mediators increased endothelial F‐actin production, however, the distribution of the actin was different. Thrombin increased the presence of stress fibers, while also decreasing peripheral banding actin. In contrast, histamine had no effect on peripheral actin compared to control, but did increase the presence of F‐actin stress fibers.

Conclusions: These results establish that thrombin and histamine alter endothelial F‐actin production in different locations within the cell, which can be quantified using an image analysis program.
The Microcirculation and Inflammation: Site of Action for Glucocorticoids
Authors: PERRETTI MAURO , AHLUWALIA AMRITA
Published: January 2010

The glucocorticoid hormones and their synthetic derivatives are potent suppressors of inflammatory and allergic pathologies. Their widespread efficacy is the result of multiple modes of action occuring predominantly at the level of the microcirculation. Indeed the glucocorticoids interfere with the function of all of the cellular components of the microcirculation associated with an inflammatory response. These agents inhibit vasodilatation of the arteriolar and capillary beds, therefore preventing the increase in blood flow that characterizes the initial stages of the inflammatory response. They also prevent increases in vascular permeability in the capillary and post‐capillary venule, thereby reducing exudate formation. Finally, the glucocorticoids potently suppress leukocyte emigration across post‐capillary venules. However, this promiscuity of the glucocorticods to act at multiple sites also endows this class of drugs with major side effects associated with chronic treatment. We propose that one way to progress forward is to understand better the effects of glucocorticoids within the microcirculation. This may aid identification of specific molecular sites of action and therefore the development of novel glucocorticoid molecules with fewer side effects.
Nitric Oxide Protects Venules Against Histamine‐Induced Leaks
Authors: AL‐NAEMI HAMDA , BALDWIN ANN L.
Published: January 2010

Objective: The goal of the present study was to investigate the prophylactic role of nitric oxide (NO) in the mesenteric microvasculature in preventing microvascular leakage subsequent to histamine application, and to evaluate the response of mast cells during these conditions.

Methods: Regions of the rat mesenteric microcirculation were flushed free of blood and pretreated with either the nitric oxide donor sodium nitroprusside (SNP 10−6 M) or Hepes‐buffered saline containing 0.5% bovine serum albumin (HBS‐BSA) for 15 minutes, then exposed to histamine (10−3 M) for another three minutes. In another set of experiments, the microvasculature was treated with either histamine (10−3 M) for three minutes or SNP (10−6 M) for 15 minutes. A control group was treated with HBS‐BSA for 15 minutes.

Results: The protective role of NO was evaluated by its ability to reduce or prevent histamine‐induced venular leaks. Mesenteric microvessels pretreated with SNP before histamine suffusion showed a significant decrease in both area and number of venular leaks following the perfusion of fluorescein isothiocyanate‐labeled bovine serum albumin (FITC‐BSA). Although SNP pretreatment did not reduce the percentage of mast cells that degranulated in the presence of histamine, it did somewhat reduce the severity of the degranulation.

Conclusion: This study demonstrated that nitric oxide availability protects mesenteric venules against histamine‐induced leaks, but does not prevent degranulation of mast cells. Therefore, nitric oxide probably acts directly on venular endothelial cells to prevent leak formation.
Expression of Endothelial Cell Adhesion Molecules in Neovascularized Tissue
Authors: VALLIEN GINA , LANGLEY ROBERT , JENNINGS STEPHEN , SPECIAN ROBERT , GRANGER D. NEIL
Published: January 2010

Objective: Recent studies indicate that endothelial cells of newly formed blood vessels are activated and exhibit a distinct phenotype that may influence the responses of these microvessels to an inflammatory stimulus. The objective of this study was to compare the basal and cytokine‐stimulated expression of endothelial cell adhesion molecules in neovascularized tissue to normal (nonproliferating) vascular beds.

Methods: The expression of P‐ and E‐selectin, VCAM‐1, ICAM‐1, ICAM‐2, and PECAM‐1 was measured, using the dual radiolabeled mAb technique, in subcutaneously implanted (for 10–15 days) polyurethane sponges, skin, heart, lung, and intestine of male C57BL/6 mice (background).

Results: Basal values of PECAM‐1 and ICAM‐2 revealed a low vascular density in the implanted sponge matrices that is comparable to skin. When normalized for vascular surface area (PECAM‐1 or ICAM‐1 expression), the basal level of E‐ and P‐selectin expression was highest in neovascularized sponge and skin. TNF‐α elicited an increased expression of all endothelial CAMs, except PECAM‐1 and ICAM‐2, but the responses were blunted in sponge and skin, relative to other vascular beds.

Conclusions: These findings indicate that endothelial cells in newly formed blood vessels exhibit a pattern of basal and cytokine‐induced expression of certain adhesion glycoproteins that is similar to nonproliferating cutaneous vessels.
Possible Steps Involved in the Transition to Stationary Adhesion of Rolling Neutrophils: A Brief Review
Authors: SMITH C. WAYNE
Published: January 2010

The transition from rolling to firm adhesion is a phenomenon frequently observed when neutrophils are interacting with activated endothelium in vitro or in vivo under physiologically relevant shear stress. The mechanisms leading to this activation are poorly understood, though selectin‐dependent tethering and CD18‐integrin‐dependent adhesion are known to be involved. This transition may involve a sequence of interactions that trigger sufficient integrin activation to allow cell arrest under flow. Recent evidence is reviewed in support of the concept that integrin (Mac‐1 and LFA‐1) activation results from signaling that occurs through selectin binding, chemotactic factor stimulation, and, possibly, LFA‐1 binding.
Signal Transduction Pathways in Enhanced Microvascular Permeability
Authors: YUAN SARAH Y.
Published: January 2010

We have been investigating the molecular mechanisms underlying pathophysiological regulation of microvascular permeability on isolated venules and cultured venular endothelial monolayers. Physiological approaches have been employed in combination with molecular analyses to probe the signal transduction pathways leading to enhanced microvascular permeability. A newly developed technique of protein transfection into cells and intact microvessels enables the correlation of functional reactions and signaling events at the molecular level in a direct and specific fashion. The results indicate that inflammatory mediators increase microvascular permeability via intracellular signaling pathways involving the activation of phospholipase C, cytosolic calcium, protein kinase C, nitric oxide synthase, guanylate cyclase, and protein kinase G. In response to the signaling stimulation, complex biochemical and conformational reactions occur at the endothelial structural proteins. Specifically, myosin light‐chain activation‐mediated myosin light‐chain phosphorylation can result in cell contraction. VE‐cadherin and β‐catenin phosphorylation may induce dissociation of the junctional proteins and their connection to the cytoskeleton, leading to a loose or opened intercellular junction. Focal adhesion phosphorylation and redistribution further provide an anchorage support for the conformational changes in the cells and at the cell junction. The three processes may act in concert to facilitate the flux of fluid and macromolecules across the microvascular endothelium.
Heterogeneous Distribution of Tumor Blood Supply Affects the Response to Chemotherapy in Patients with Head and Neck Cancer
Authors: GALMARINI FELIPE C. , GALMARINI CARLOS M. , SARCHI MARÍA I. , ABULAFIA JORGE , GALMARINI DARÍO
Published: January 2010

Objective: To evaluate if the heterogeneous distribution of tumor blood supply affects the response to chemotherapy in patients with head and neck cancer.

Methods: We treated 25 stage III/IV patients with an intraarterial cisplatinum‐bleomycin regimen. Prior to treatment, a blue dye was injected directly to tumors through the catheter. Well‐stained areas were considered as profusely perfused areas whereas poorly stained areas were considered as poorly perfused areas. Biopsies of both areas of each tumor were taken prior to and after the treatment and the histopathological response was evaluated with the following grading: I, tumor disappearance; II, destruction of some tumor nests; III, no changes.

Results: Grade I responses were attained in 13/25 (52%) of profusely perfused areas against 1/25 (4%) of poorly perfused areas (p < 0.001). Moreover, there were significant differences (p < 0.001) in the overall responses: 21/25 (84%) in the profusely perfused areas versus 7/25 (28%) in the poorly perfused areas; and in grade III responses (4/25, 16% vs. 18/25, 72%). To determine a possible correlation between the histopathological responses obtained in profusely perfused and in poorly perfused areas of each tumor, we then calculated the Kendall's tau‐b statistics, obtaining a τ value of 0.279 (p = 0.145). This data indicated that histopathological responses to chemotherapy of profusely perfused and poorly perfused areas were independent in each tumor.

Conclusions: Heterogeneity in the distribution of tumor blood supply affects the response to chemotherapy by influencing the intratumoral delivery of therapeutic agents. After the administration of effective doses of anticancer drugs to a tumor, cells in profusely perfused areas receive enough to destroy them while cells in the poorly perfused areas are exposed to lower drug concentrations and, therefore, survive. This phenomenon could explain in part the difficulty in the treatment of human solid tumors.
New Method for Imaging Innervation of the Renal Preglomerular Vasculature. Alterations in Hypertensive Rats
Authors: CASELLAS DANIEL , BOURIQUET NATHALIE , ARTUSO ANNIE , WALCOTT BENJAMIN , MOORE LEON C.
Published: January 2010

Objective: To develop a new method for viewing adrenergic innervation along renal preglomerular vessels; to assess nerve densities and vascular lesions along arcuate arteries (ArcA), arcuate arterial branches (ArcB), and interlobular arteries (ILA) in spontaneously hypertensive rats (SHR) and in angiotensin II (AngII) and in NG‐nitro‐l‐arginine methyl ester (l‐NAME) hypertensive rats.

Methods: Preglomerular vasculatures were isolated after HCl maceration and were immunostained against synaptophysin, a membrane protein of synaptic vesicles. Lesions were stained with Sudan black. Longitudinal nerve densities and relative frequencies of ArcA, ArcB, and ILA endowed with sudanophilic lesions were assessed separately.

Results: Synaptophysin immunostaining revealed the vascular neural plexus. Nerves were adrenergic, as the plexus was destroyed by treatment with 6‐hydroxy dopamine. Vascular lesions were not seen in SHR, and increased nerve density was observed along ArcA and ILA. In l‐NAME‐ and AngII‐hypertensive rats, vascular lesions affected predominantly ArcB and ILA, and nerve density was reduced by 12% and 28% (ArcA), 37% and 31% (ArcB), and by 55% and 34% (ILA), respectively, versus normotensive controls. Endothelin‐1 receptor blockade did not affect AngII‐induced hypertension but prevented both lesion development and reduction of density of the vascular neural plexus.

Conclusions: The method we have devised provides a direct en face view of the vascular adrenergic innervation of isolated preglomerular vasculature. Measurements in hypertensive rat models suggest a link between vascular lesions and reduction in nerve density in hypertension. Endothelin‐1 likely plays a key role in mediating both vascular injury and altered vascular nerve density in hypertension.
Microcirculatory Inflammation in Chronic Venous Insufficiency: Current Status and Future Directions
Authors: DURÁN WALTER , PAPPAS PETER J. , SCHMID‐SCHÖNBEIN GEERT W.
Published: January 2010

One of the hallmarks of chronic venous insufficiency (CVI) is an elevated venous pressure. However, no direct link at the cellular and molecular levels between venous hypertension and actual tissue damage in CVI has been established. Evidence for generation of an inflammatory reaction and several molecular alterations in the development of CVI is discussed. Development of experimental models of CVI, analysis of the mechanical tissue stresses in addition to venous hypertension, in combination with systematic studies of clinically stratified and standardized patient‐derived samples is required for molecular description of the pathogenesis of CVI.
Edward H. Bloch, M.D., Ph.D. Pioneer in the Microscopic Study of, and the Microcirculation of, Living Tissues and Organs
Authors: McCUSKEY ROBERT S.
Published: January 2010

Edward H. Bloch, M.D., Ph.D., Professor Emeritus of Anatomy, School of Medicine, Case Western Reserve University, died 3 November 2000 in Cleveland, Ohio at the age of 86. Known to his friends as “Maxl,” he will be greatly missed by his friends, colleagues and former students.
Chronic Vasodilation Induces Matrix Metalloproteinase 9 (MMP‐9) Expression during Microvascular Remodeling in Rat Skeletal Muscle
Authors: van GIESON ERIC J. , SKALAK THOMAS C.
Published: January 2010

Objective: The process of microvessel growth and remodeling depends on the presence of matrix metalloproteinases (MMPs) in a specific spatial pattern of expression. This study characterizes the spatial distribution of metalloproteinase‐9 (MMP‐9) expression during microvascular remodeling in the rat spinotrapezius muscle.

Methods: Female Sprague‐Dawley rats (4 weeks old) were administered the α1‐adrenergic blocker prazosin for 7 days to induce chronic vasodilation and associated increases in capillary and arteriolar density. MMP‐9 expression was analyzed by Western blotting analysis of microdissected regions of muscle and immunolabeling of muscle sections.

Results: Capillary density expressed as both capillary‐to‐fiber ratio (C/F) and capillaries per mm2 increased significantly (p < 0.01) due to prazosin administration. Western blotting on microdissected regions of spinotrapezius muscle showed that there was an increase in MMP‐9 expression in prazosin‐treated animals. Additionally, the Western blots showed a presence of the activated form of MMP‐9 in regions of spinotrapezius muscle containing vessels on the order of capillaries and small arterioles. Immunohistochemistry demonstrated that MMP‐9 significantly increased in the muscles of treated animals in areas within the vessel walls of microvessels greater than 20 µm in diameter. However, interstitial MMP‐9 expression did not significantly increase with prazosin administration.

Conclusions: These results demonstrate that the expression of MMP‐9 increases during in vivo microvascular remodeling in adult skeletal muscle. The MMP‐9 expression is limited to larger (>20‐µm diameter) microvessels, suggesting a role for MMP‐9 in the remodeling of such vessels during prazosin‐induced vasodilation and the subsequent capillary proliferation.
Mechanisms of Leukocyte Sequestration in Inflamed Lungs
Authors: DOERSCHUK CLAIRE M.
Published: January 2010

The lungs are an important site of host defense. The capillary blood contains an increased concentration of neutrophils and other leukocytes compared with large vessels, due to the structure of the pulmonary capillary bed, the diameter of spherical leukocytes, and their poor deformability compared with erythrocytes. During inflammation within the distal airways, neutrophils sequester within the pulmonary capillaries and emigrate into the parenchyma. This sequential process involves complex events regulating interactions between mechanical and adhesive properties of both neutrophils and endothelial cells. Initial changes in the cytoskeleton may stiffen the neutrophils and prevent them from deforming, while subsequent dynamic cytoskeletal remodeling of neutrophils and endothelial cells results in crawling and transendothelial migration. Emigration of neutrophils can occur through at least two adhesion pathways: one that requires the CD11/CD18 adhesion complex and one that does not. Which pathway is selected is determined by the stimulus and the signaling pathways that are initiated. Migration through the alveolo‐capillary wall is also highly regulated. Neutrophils released from the bone marrow traffic first through the pulmonary microvasculature, and the phenotype of these newly released neutrophils impacts pulmonary host defense. The many recent studies underline the complexity of neutrophil responses and host defense and the uncertainties of our knowledge.
Tetraspanins and Intercellular Interactions
Authors: YÁÑEZ‐MÓ MARÍA , MITTELBRUNN MARÍA , SÁNCHEZ‐MADRID FRANCISCO
Published: January 2010

The superfamily of tetraspanins comprises a group of polypeptides with four transmembrane domains that form large supramolecular structures in the plasma membrane through their associations to multiple integral membrane proteins. They are involved in homo‐ and heterotypic intercellular interactions in different processes such as hematopoiesis, lymphocyte activation, cancer metastasis, and fertilization. Intercellularly located tetraspanins regulate the juxtacrine activity of growth factors, cell fusion, and myelin formation. On the other hand, in motile cells they relocalize from cell‐cell junctions to actin‐based structures such as filopodia or growth cones and regulate cell motility in wound healing and angiogenesis processes.
Migration of Leukocytes across Endothelial Junctions: Some Concepts and Controversies
Authors: MULLER WILLIAM A.
Published: January 2010

This article is not meant to be a comprehensive review of leukocyte migration or endothelial cell junctions. Rather, I have chosen some aspects of inflammation that might be of general interest to vascular biologists and have focused on the structural and molecular elements of the endothelial junction involved in these processes. These are all active (and some controversial) areas of investigation. I have tried to objectively present both sides of any controversies, while stating at the end the general consensus of the field.
Vascular Dysfunction Induced by AGE is Mediated by VEGF via Mechanisms Involving Reactive Oxygen Species, Guanylate Cyclase, and Protein Kinase C
Authors: IDO YASUO , CHANG KATHERINE C. , LEJEUNE WANDA S. , BJERCKE ROBERT J. , REISER KAREN M. , WILLIAMSON JOSEPH R. , TILTON RONALD G.
Published: January 2010

Objective: These experiments were designed to elucidate mechanisms mediating vascular dysfunction induced by advanced glycation end products (AGEs).

Methods: Skin chambers were mounted on the backs of Sprague‐Dawley rats and 1 week later, granulation tissue that formed in the bottom of the chamber was exposed twice daily for 7 days to glycated rat serum albumin in the presence and absence of inhibitors of reactive oxygen intermediates, nitric oxide synthase and guanylate cyclase, protein kinase C (PKC), and a neutralizing vascular endothelial growth factor (VEGF) antibody. Vascular 125I‐albumin clearance and blood flow were quantified by use of a double isotope‐dilution technique and radiolabeled microspheres, respectively.

Results: Albumin permeation and blood flow were increased dose‐dependently to a maximum of 2 to 3 times controls by increasing the extent of glucose modification, the concentration, or the duration of exposure to glycated albumin. These increases were significantly attenuated by probucol and superoxide dismutase; NG‐nitro‐l‐arginine‐methyl ester (l‐NAME), a nitric oxide synthase inhibitor; LY83583, a guanylate cyclase inhibitor; and LY333531, a β‐isoform‐selective protein kinase C inhibitor. A neutralizing VEGF monoclonal antibody also markedly attenuated the permeability and blood flow increases induced by glycated albumin.

Conclusions: These observations indicate potentially important roles for oxygen free‐radicals and nitric oxide in mediating permeability and blood flow changes induced by glycated proteins via mechanisms involving increased protein kinase C activity and VEGF production. Striking similarities in the mechanism by which hyperglycemia and glycated proteins induce vascular dysfunction suggest that a common pathway mediates effects of these different metabolic imbalances on vascular dysfunction.
Mediation of EDHF‐Induced Reduction of Smooth Muscle [Ca2+]iand Arteriolar Dilation by K+Channels, 5,6‐EET, and Gap Junctions
Authors: UNGVARI ZOLTAN , KOLLER AKOS
Published: January 2010

Objective: To characterize the role of K+channels, the cytochrome P‐450 (CYP) metabolite 5,6‐EET, and gap junctions in modulation of arteriolar myogenic tone by a non‐nitric oxide nonprostaglandin mediator, termed “endothelium‐dependent hyperpolarizing factor” (EDHF), released to acetylcholine (ACh) in skeletal muscle arterioles.

Methods: In isolated rat gracilis arterioles, simultaneous changes in smooth muscle (aSM) [Ca2+]i(assessed by changes in fura‐2 ratiometric signal, RCa) and diameter were measured in response to ACh in the presence of indomethacin andl‐NAME.

Results: ACh, the KATPchannel opener pinacidil, and the Ca2+channel inhibitor verapamil elicited comparable decreases in aSM [Ca2+]i(max.: −32 ± 3%, 29 ± 3%, and −30 ± 3%, respectively) and arteriolar dilations (max.: 90 ± 4%, 96 ± 2%, and 95 ± 2%, respectively). ACh‐induced responses were inhibited by KCl‐depolarization, KCachannel blockers (TEA, charybdotoxin), or gap junction inhibitors (18α‐glycyrrhetinic acid, hyperosmolar sucrose). The KATPchannel inhibitor glibenclamide, the KIRchannel inhibitor barium chloride, or the CYP inhibitor 17‐octadecynoic acid (ODYA) were without effect. The putative EDHF analogue 5,6‐EET elicited constrictions in the presence of the endothelium that could be prevented by indomethacin or a TxA2receptor antagonist, whereas in the absence of the endothelium, EDHF elicited only small, charybdotoxin‐insensitive decreases in aSM RCaand dilations (max.: −8 ± 2% and 27 ± 4%, respectively).

Conclusions: In skeletal muscle arterioles, EDHF 1) substantially and rapidly reduces myogenic tone by decreasing aSM [Ca2+]ivia opening KCachannels, 2) it is unlikely to be 5,6‐EET or other CYP metabolites, but 3) requires functional gap junctions.
Immunological Basis of Inflammatory Bowel Disease: Role of the Microcirculation
Authors: LAROUX F. STEPHEN , GRISHAM MATTHEW B.
Published: January 2010

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the intestine and/or colon of unknown etiology in which patients suffer from severe diarrhea, rectal bleeding, abdominal pain, fever, and weight loss. Active episodes of IBD are characterized by vasodilation, venocongestion, edema, infiltration of large numbers of inflammatory cells, and erosions and ulcerations of the bowel. It is becoming increasingly apparent that chronic gut inflammation may result from a dysregulated immune response toward components of the normal intestinal flora, resulting in a sustained overproduction of proinflammatory cytokines and mediators. Many of these Th1 and macrophage‐derived cytokines and lipid metabolites are known to activate microvascular endothelial cells, thereby promoting leukocyte recruitment into the intestinal interstitium. This review discusses the basic immune mechanisms involved in the regulation of inflammatory responses in the gut and describes how a breakdown in this protective response initiates chronic gut inflammation.