bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of a large general practice syndromic surveillance system to monitor the progress of the influenza A(H1N1) pandemic 2009 in the UK
Authors: HARCOURT S. E. , SMITH G. E. , ELLIOT A. J. , PEBODY R. , CHARLETT A. , IBBOTSON S. , REGAN M. , HIPPISLEY-COX J.
Published: April 2011

The Health Protection Agency/QSurveillance national surveillance system utilizes QSurveillance® a recently developed general practitioner database covering over 23 million people in the UK. We describe the spread of the first wave of the influenza A(H1N1) pandemic 2009 using data on consultations for influenza-like illness (ILI), respiratory illness and prescribing for influenza from 3400 contributing general practices. Daily data, provided from 27 April 2009 to 28 January 2010, were used to give a timely overview for those managing the pandemic nationally and locally. The first wave particularly affected London and the West Midlands with a peak in ILI in week 30. Children aged between 1 and 15 years had consistently high consultation rates for ILI. Daily ILI rates were used for modelling national weekly case estimates. The system enabled the ‘real-time’ monitoring of the pandemic to a small geographical area, linking morbidity and prescribing for influenza and other respiratory illnesses.
Writing the History of Development: A Review of the Recent Literature
Authors: FREY MARC , KUNKEL SÖNKE
Published: April 2011

‘Development’ as a ‘process of enlarging people's choices’ is omnipresent. Constituents of global society – governments, international organisations, non-governmental organisations (NGOs), multinational corporations, the media and individual actors – are deeply involved in its practices and discourses. At universities around the world, development studies mushroom, and development research has become a darling of the social sciences. In particular, development assistance has become big business, involving the flow of $136 billion dollars in 2009. But more significantly than before, development issues and especially development assistance have become contested terrain, too. While the millennium development goals defined by the United Nations in 2000 and designed to halve global poverty by the year 2015 call on donor and recipient countries to increase their efforts, critics of development assistance are multiplying.
Bridging the Gap: Pracademics in Foreign Policy
Authors: Murphy Ann Marie , Fulda Andreas
Published: April 2011

In his seminal workBridging the Gap: Theory and Practice in Foreign Policy, Alexander George (1993) lamented the great divide between academia and the foreign policymaking community, arguing that greater interaction between scholars and policymakers would produce better policy. We share George's belief that scholars and practitioners each have much to offer the other. In fact, a wide spectrum of opportunities exists for scholars in the field of political science to engage in meaningful public service that can enhance every aspect of their careers, as well as contribute to international understanding.
Participant Observation and the Political Scientist: Possibilities, Priorities, and Practicalities
Authors: Gillespie Andra , Michelson Melissa R.
Published: April 2011

Surveys, experiments, large-N datasets and formal models are common instruments in the political scientist's toolkit. In-depth interviews and focus groups play a critical role in helping scholars answer important political questions. In contrast, participant observation techniques are an underused methodological approach. In this article, we argue that participant observation techniques have played and should continue to play a key role in advancing our understanding of political science. After demonstrating the use of these techniques, we offer readers advice for embarking upon participant observation research and explain how this approach should fit into a scholar's long-term career plans.
Wikipedia as a Data Source for Political Scientists: Accuracy and Completeness of Coverage
Authors: Brown Adam R.
Published: April 2011

In only 10 years, Wikipedia has risen from obscurity to become the dominant information source for an entire generation. However, any visitor can edit any page on Wikipedia, which hardly fosters confidence in its accuracy. In this article, I review thousands of Wikipedia articles about candidates, elections, and officeholders to assess both the accuracy and the thoroughness of Wikipedia's coverage. I find that Wikipedia is almost always accurate when a relevant article exists, but errors of omission are extremely frequent. These errors of omission follow a predictable pattern. Wikipedia's political coverage is often very good for recent or prominent topics but is lacking on older or more obscure topics.
Walter Owen Filley
Authors: Stratford Michael C.
Published: April 2011

Walter Owen Filley, Jr., passed away on March 23, 2010, at age 89 in Manchester Center, Vermont, where he had lived for seven years in an assisted living facility. Born in New Haven, Connecticut, on September 22, 1920, he attended New Haven High School and graduated from the the Choate School in 1937. He then spent a year as an exchange student sponsored by Choate in a South German school. He received his BA from Yale in 1942 before joining the Army for three years, serving mostly as a sergeant in the Counterintelligence Corps with the 2nd Armored Division in Western Europe from 1944 to 1945.
Frank Tachau
Authors: Johnson Richard , Simpson Dick , Tepe Sultan
Published: April 2011

Frank Tachau, one of the leading scholars of Middle Eastern politics, died on July 23, 2010, at the age of 80 in Sykesville, Maryland, after battling with multiple myeloma for two years. Born in Braunschweig, Germany, Professor Tachau moved with his family to Chicago at the age of seven in 1936. He studied at the University of Chicago, earning a bachelor's and a master's degree in political science. His MA thesis on the diplomacy of the Turkish Straits between 1936 and 1946 led to his remarkable Ph.D. dissertation, which offered one of the first scholarly accounts of Turkish nationalism in 1958. What distinguished Professor Tachau's analyses from others studying the Middle East was his extensive ethnographic work in the region. His unique language skills allowed him to learn modern Turkish very quickly in 1956 and opened the door for him to master historical Ottoman Turkish as well. During his multiple visits to the region, Professor Tachau studied the history of the Ottoman Empire and also noted the emerging institutions of the new Turkish republic. His extensive stays in the region equipped him with unique insights into the views of the country's political elite and the mechanisms of its fledgling democracy.
“The Politics of Rights”: APSA 107th Annual Meeting and Exhibition
Authors: West Lauren G.
Published: April 2011

For the first time in its history, the Annual Meeting of the American Political Science Association will take place in Seattle, Washington. Join APSA in this exciting new location to address the latest scholarship in political science and connect with colleagues from around the world. Convening in a contemporary urban environment surrounded by the natural beauty of the Pacific Northwest, the 2011 Annual Meeting and Exhibition will have something for scholars at every stage of their careers. 7,000 political scientists are expected to travel to Seattle to take part in this premier event in the field.
Report of the Editor of Perspectives on Politics, 2009–2010
Authors: Isaac Jeffrey C. , Moskowitz James
Published: April 2011

I am happy to report that Perspectives on Politics is thriving. We inherited a journal that was founded with a flourish in response to a range of concerns about the ways in which the U.S. political science profession had become highly specialized and balkanized, at the expense of broader understanding and public relevance. Our editorial predecessors had put the journal on a sound footing, a significant accomplishment for a new journal less than a decade old. At the same time, the journal we inherited faced some challenges related to the effective use of the Editorial Manager system; the efficiency of its operations, especially regarding communication with authors and reviewers; and its distinctive purposes and intellectual vision looking to the future. In the roughly 18 months since we assumed editorial control of the journal in June 2009, I believe that we have succeeded in addressing these challenges and projecting a new excitement about the journal and the role it can play in contributing to the invigoration of the discipline.
Multispectral Infrared Reflectography to Differentiate Features in Paintings
Authors: Daffara Claudia , Fontana Raffaella
Published: April 2011

Infrared reflectography is a well-known technique based on wideband imaging in the near-infrared (NIR) range used for painting diagnostics in conservation laboratories.. This work is focused on the application of multiband reflectography for analysis of pictorial layers and differentiated detection of painting features. This technique generates a set of narrowband NIR images of the painting. Starting from a dataset that is registered, metrically correct, and calibrated, the capability of collecting both spectral and spatial information has been exploited by processing the image cube with interplane techniques. Examples on artworks by Caravaggio, Veronese, Bronzino, and Schiavone are presented.
Hematopoietic Derived Cell Infiltration of the Intestinal Tumor Microenvironment inApcMin/+Mice
Authors: Davis Celestia , Price Robert , Acharya Grishma , Baudino Troy , Borg Thomas , Berger Franklin G. , Peña Maria Marjorette O.
Published: April 2011

Tumors consist of a heterogeneous population of neoplastic cells infiltrated by an equally heterogeneous collection of nonneoplastic cells that comprise the tumor microenvironment. Tumor growth, invasion, and metastasis depend on multiple interactions between these cells. To assess their potential as therapeutic targets or vehicles for tumor specific delivery of therapeutic agents, we examined the contribution of bone marrow derived cells (BMDCs) to the intestinal tumor microenvironment. Hematopoietic stem cells expressing the enhanced green fluorescent protein (eGFP) were transplanted into lethally irradiatedApcMin/+mice, and their engraftment was analyzed by confocal microscopy. The results showed abundant infiltration of eGFP cells into the small intestine, colon, and spleen compared to heart, muscle, liver, lung, and kidney. Within the intestine, there was a pronounced gradient of engraftment along the anterior to posterior axis, with enhanced infiltration into adenomas. Immunofluorescence analysis showed that osteopontin was expressed in tumor stromal cells but not in nontumor stromal populations, suggesting that gene expression in these cells is distinct. Tumor vasculature inApcMin/+mice was chaotic compared to normal intestinal regions. Our data suggest that BMDCs can be harnessed for tumor-targeted therapies to enhance antitumor efficacy.
THE GELFAND SPECTRUM OF A NONCOMMUTATIVE C*-ALGEBRA: A TOPOS-THEORETIC APPROACH
Authors: HEUNEN CHRIS , LANDSMAN NICOLAAS P. , SPITTERS BAS , WOLTERS SANDER
Published: April 2011

We compare two influential ways of defining a generalized notion of space. The first, inspired by Gelfand duality, states that the category of ‘noncommutative spaces’ is the opposite of the category of C*-algebras. The second, loosely generalizing Stone duality, maintains that the category of ‘point-free spaces’ is the opposite of the category of frames (that is, complete lattices in which the meet distributes over arbitrary joins). Earlier work by the first three authors shows how a noncommutative C*-algebra gives rise to a commutative one internal to a certain sheaf topos. The latter, then, has a constructive Gelfand spectrum, also internal to the topos in question. After a brief review of this work, we compute the so-called external description of this internal spectrum, which in principle is a fibred point-free space in the familiar topos of sets and functions. However, we obtain the external spectrum as a fibred topological space in the usual sense. This leads to an explicit Gelfand transform, as well as to a topological reinterpretation of the Kochen–Specker theorem of quantum mechanics.
The Influence of the Weather on Affective Experience
Authors: Kööts Liisi , Realo Anu , Allik Jüri
Published: April 2011

This study examined the relationship between affective experiences and weather variables using an experience-sampling method. The moderating effects of personality and age on the relationship were also investigated. Two age groups of participants (students and elderly people) recorded their moods when signalled during 14 consecutive days on 7 randomly determined occasions per day. Hourly weather data (temperature, relative humidity, barometric pressure, and luminance) for the same period were obtained from the local weather station. Previously participants had completed the Estonian versions of the Revised NEO Personality Inventory ( Kallasmaa, Allik, Realo, & McCrae, 2000 ) and the Positive and Negative Affect Schedule ( Allik & Realo, 1997 ). Multilevel random coefficient modeling analyses showed that momentary ratings of positive and negative affect were weakly related to temperature, positive affect was also related to sunlight. However, momentary ratings of fatigue showed a distinct tendency for greater incidence of sleepiness in the cold and dark. Age group was one of the most important moderators of the weather-emotion models. The influence of weather on emotions interacted with being outdoors. Personality traits also explained a small portion of variance in the influence of weather on affective states.
Influence of temperature variations on the noise level of the data of the LaCoste and Romberg Earth tide gravity meter ET18
Authors: Hegewald Anne , Jentzsch Gerhard , Jahr Thomas
Published: April 2011

Gravity records include a wide spectrum of signals based on mass changes in the Earth's crust. Today, the detectable amplitudes of the signals of interest become smaller and smaller (e.g., hydrological effects). From this it follows that the accuracy and resolution of measurements must be very high and the noise level as low as possible. In this study, the influence of the temperature variations as noise signal in the gravity records was investigated. Therefore, two 215 day time series of the LaCoste and Romberg gravity meter ET18 in the broadband Geodynamical Observatory Moxa were analyzed and compared. Each time series was recorded in another room. The first room is characterized by a temperature variation of ±4°C per year. The second room has a constant temperature of 19°C. As reference data, the parallel recorded time series of the superconducting gravity meter (SG) CD‐034, installed in the temperature‐stabilized room were used. The result of this study shows a clear influence of temperature variation on the noise level in the spectra of the ET18 compared to the SG spectra. Depending on the frequency ranges, the ratios of the noise levels of the ET18 and SG spectra are between 2 and 5. In the frequency range up to 0.01 cph the ET18/SG factor is 2, between 0.01 cph and 0.09 cph the factor is 3, and above 0.09 cph the factor is 5.
MCL1 meets its end during mitotic arrest
Authors: Millman Scott E , Pagano Michele
Published: April 2011

Evidence for the destruction of the anti‐apoptotic protein MCL1 during prolonged mitotic arrest comes from three papers, one in The EMBO Journal and two in Nature, thus shedding light on the mechanism of apoptosis induction under these conditions.
The in vivo Autoradiographic Measurement of Regional Cerebral Blood Flow Using Stable Xenon and Computerized Tomography: The Effect of Tissue Heterogeneity and Computerized Tomography Noise
Authors: Rottenberg D. A. , Lu H. C. , Kearfott K. J.
Published: April 2011

We have studied the effect of brain tissue (gray matter–white matter) heterogeneity and computerized tomography (CT) noise on the accuracy of xenon CT measurements of regional cerebral blood flow (rCBF) based upon “autoradiographic” and multiple-scan washin protocols, The results of our mathematical analysis indicate that both protocols are associated with a variety of measurement errors that lead to unacceptable and, to a large extent, unpredictable uncertainties in calculated values of rCBF. Brain tissue heterogeneity and high volumetric flow rates may—even in the absence of movement artifact and CT noise—lead to measurement errors in excess of 20%. Moreover, CT noise is additive in regard to these errors, and constitutes the most confounding variable of all.
Nomogram for 2-Deoxyglucose Lumped Constant for Rat Brain Cortex
Authors: Pardridge William M. , Crane Paul D. , Mietus Lawrence J. , Oldendorf William H.
Published: April 2011

The quantitation of local cerebral metabolic rate of glucose with the 2-deoxyglucose technique of Sokoloff requires the use of a correction factor, or lumped constant. We have shown previously (Pardridge et al., 1982) that a simple model may be formulated to predict changes in the lumped constant that occur due to alterations in the distribution of glucose and 2-deoxyglucose in brain. Given experimentally observed values for brain and plasma glucose concentrations, the 2-deoxyglucose lumped constant may be determined from a nomogram constructed from knowledge of the blood–brain barrier transport constants (KM, Vmax, KD) for glucose and for 2-deoxyglucose. However, the nomogram is constructed from transport constants determined in the barbiturate-anesthetized state. The applicability of the nomogram to other physiologic states was examined in the present studies. Large changes in blood–brain barrier hexose transport constants do not appreciably alter the shape of the nomogram, if the changes in KM or Vmax for glucose or for 2-deoxyglucose are the same. Moreover, glucose and 2-deoxyglucose are both transported by the same hexose carrier, and selective changes in the transport of only one hexose have not been reported. Therefore, it is probable that the nomogram constructed from transport constants measured under barbiturate anesthesia is useful in predicting the lumped constant in a variety of physiologic states.
Influence of Blood Glucose Concentration on Brain Lactate Accumulation during Severe Hypoxia and Subsequent Recovery of Brain Energy Metabolism
Authors: Gardiner Mark , Smith Maj-Lis , Kågström Erik , Shohami Esther , Siesjö Bo K.
Published: April 2011

The effects of hypoxaemia on regional cerebral blood flow (CBF) and brain cortical metabolite concentrations were investigated at different blood glucose concentrations in rats under nitrous oxide anaesthesia. Tissue hypoxia of 15-min duration was induced by a combination of arterial hypoxaemia, hypotension, and clamping of the right carotid artery. Blood glucose concentrations were manipulated by varying the food intake in the 24 h before the experiment, and by glucose administration. Cortical CBF doubled during hypoxia on the intact side, but did not differ significantly from control values on the clamped side. In the clamped hemisphere there was a substantial decrease in adenylate energy charge. At brain tissue glucose concentrations of 1 μmol g−1 and above, there was an inverse correlation between adenylate energy charge and brain lactate concentration. In starved animals with mean brain glucose of 0.32 ± 0.00 μmol g−1, lactate concentration was significantly lower, in spite of equally severe disruption of energy state. Recovery of brain adenylate energy charge was worse in fed and glucose-infused groups than in the fasted group. These results demonstrate that limitation of substrate supply during severe hypoxia in the rat allows enhanced recovery of brain energy metabolism following the hypoxic episode.
Effect of Nitrous Oxide on Local Cerebral Glucose Utilization in Rats
Authors: Ingvar Martin , Siesjö B. K.
Published: April 2011

The influence of 70–80% N2O on local local cerebral glucose utilization (CMRg1) in the rat brain was studied with the [14C]deoxyglucose method in minimally restrained, spontaneously breathing animals 75 min following discontinuation of halothane anaesthesia. Nitrous oxide was found to have only small effects on local CMRg1 in the majority of the 25 structures analyzed. When corrections were made for a small difference in body temperature between nitrous oxide–breathing animals and those breathing air, nitrous oxide was found to significantly increase local CMRg1 in some subcortical structures by 15–25% (red nucleus, thalamus, geniculate bodies, and superior colliculus), and to decrease local CMRg1 in nucleus accumbens and sensorimotor cortex by comparable amounts. Thus, although nitrous oxide does not alter overall glucose utilization in the brain, it differentially affects CMRg1 in some brain structures.
Effect of Apomorphine on the Relationship between Local Cerebral Glucose Utilization and Local Cerebral Blood Flow (with an Appendix on its Statistical Analysis)
Authors: McCulloch James , Kelly Paul A. T. , Ford Ian
Published: April 2011

The alterations in local glucose utilization and local blood flow in 36 discrete regions of the central nervous system (CNS) that occur following the intravenous administration of the putative dopaminergic agonist, apomorphine (0.5 mg/kg), have been measured using the quantitative autoradiographic 14C-2-deoxyglucose and 14C-iodoantipyrine techniques. In eight of the regions examined (frontal and sensory-motor cortices, ventral thalamus, caudate nucleus, globus pallidus, substantia nigra, subthalamic nucleus, and posterior cerebellar hemisphere), significant elevations of local cerebral blood flow (CBF) were observed following apomorphine administration. In these eight regions, proportionately similar, significant elevations in local glucose utilization were observed following apomorphine. In two of the regions investigated (anterior cingulate cortex and lateral habenular nucleus), significant reductions in both local blood flow and glucose utilization were observed following apomorphine administration. In the majority of regions examined (26 of the total 36), apomorphine did not alter significantly either blood flow or glucose use. Using a statistical approach, described in detail in an appendix, the relationship between local rates of glucose utilization and local levels of tissue blood flow was analyzed. A relationship between local CBF and local glucose utilization was found following apomorphine, and the nature of this relationship was indistinguishable from that observed in control animals. In no region of the CNS was a significant deviation from the normal CBF–glucose use relationship demonstrated following apomorphine administration. These results point to the greater importance of the effects of apomorphine upon tissue metabolic activity, rather than its direct vascular action, as being the major mechanism underlying the observed alterations in local CBF. The statistical methods provide a rigorous analytical approach to the analysis of alterations in the relationship, both locally and globally, of blood supply to glucose utilization.
Prostaglandin Inhibition and Cerebrovascular Hemodynamics in Normal and Ischemic Human Brain
Authors: Okabe Takashi , Meyer John S. , Amano Takahiro , Okayasu Hiroyuki , Mortel Karl
Published: April 2011

Indomethacin is a potent inhibitor of prostaglandin synthesis. Indomethacin effects on cerebral blood flow (CBF) in normal subjects and patients with ischemic cerebrovascular disease were measured by 133Xe inhalation method and compared. Thirteen normal subjects with muscle contraction headaches were tested and compared to three groups of patients with ischemic cerebrovascular disease: (1) a transient ischemic attack (TIA) group, consisting of 8 patients, (2) a recent cerebral infarction group consisting of 10 patients with recent stroke (within 2 months), and (3) a chronic cerebral infarction group, consisting of 10 patients with remote stroke (exceeding 2 months). From the three groups, 7 patients with internal carotid artery occlusion also underwent superficial temporal artery to middle cerebral artery (STA-MCA) bypass; this group was tested before and after the operative procedure. Indomethacin induced significant CBF reductions in the TIA and chronic cerebral infarction groups but there were no significant effects in the recent cerebral infarction group and many showed paradoxical increases. Plotting indomethacin-induced CBF changes according to the time course of cerebral infarction indicated that abnormal responses gradually returned toward normal within 16 weeks. Indomethacin-induced CBF changes were measured prospectively in patients undergoing STA-MCA bypass. Indomethacin had no significant effect on CBF before the procedure, but significantly reduced CBF (i.e., mean CBF became reduced) after surgery. Comparison of the time course for recovery of indomethacin-induced CBF responses in non-operated cases indicated that the post-operative difference in response could be due to the natural history of the disease rather than to surgery. Present studies confirm that prostaglandins play an important part in cerebral vascular control in man, and that these agents are temporarily deranged following acute cerebral infarction, which may account for temporary alterations in regional cerebrovascular responsiveness to 5% CO2 and 100% O2 inhalation after stroke.
Nimodipine Improves Cerebral Blood Flow and Neurologic Recovery after Complete Cerebral Ischemia in the Dog
Authors: Steen Petter A. , Newberg Leslie A. , Milde James H. , Michenfelder John D.
Published: April 2011

Ten minutes of complete ischemia was produced in 11 dogs by temporary ligation of the aorta. Immediately before the ischemic episode, the dogs received nimodipine, a new calcium entry blocker, 10 μg kg−1, i.v., followed by an infusion of 1 μg kg−1 min−1 for 2 h. Post-ischemic cerebral blood flow and metabolism were measured for 120 min in six dogs. Neurologic recovery was evaluated 48 h post-ischemia in five dogs. The results were compared to previously determined controls. Nimodipine nearly doubled cerebral blood flow in the delayed post-ischemic hypoperfusion period, compared to untreated dogs (approximately 45% versus 25% of pre-ischemic control values), but had no significant effect on metabolism. Nimodipine also improved neurologic recovery. Four of five treated dogs were normal and one was moderately damaged, whereas six of seven controls were either severely damaged or dead. This suggests that the delayed hypoperfusion state occurring after complete cerebral ischemia probably does contribute to the ultimate neurologic damage, and that nimodipine offers a potential protective effect.
Effect of Exercise on Cerebral Circulation
Authors: Globus Mordecai , Melamed Eldad , Keren Andre , Tzivoni Dan , Granot Chaim , Lavy Sylvan , Stern Shlomo
Published: April 2011

The effect of supine physical exercise on cerebral blood flow (CBF) was measured in 30 normal subjects with the 133Xe inhalation technique. The CBF measurements were correlated to changes in Pco2, heart rate, and blood pressure, and to cardiac output and right atrial pressure in 10 of the subjects who underwent Swan-Ganz catheterization. No significant change was found in CBF during physical exercise, although a marked increase in cardiac output, blood pressure, and right atrial pressure and a mild decrease in PCO2 were found. Cerebrovascular resistance increased by 38%, in contrast to a decrease of 33% in the peripheral vascular resistance. The factors that affect the mechanism of cerebrovascular autoregulation during exercise are discussed.
Simultaneous Measurement of Local Glucose Utilization and Blood Flow in the Rat Brain: An Autoradiographic Method Using Two Tracers Labeled with Carbon-14
Authors: Furlow Thomas W. , Harrison Lynn E.
Published: April 2011

A simplified technique that uses two radionuclide tracers has been devised to measure local cerebral glucose utilization (lCGU) and local cerebral blood flow (lCBF) in the same rat. The method employs [14C]-2-deoxyglucose and [14C]iodoantipyrine to produce an autoradiogram before and another after extraction into chloroform of the [14C]iodoantipyrine from the brain sections. The chloroform-extracted autoradiogram yields lCGU, and the difference in tissue carbon-14 concentration between the two autoradiograms permits calculation of lCBF. The double-isotope technique provides values of lCGU and lCBF that are statistically indistinguishable from those derived from conventional single-isotope methods.
The Effects of Serotonin on Local Cerebral Blood Flow
Authors: Grome J. J. , Harper A. M.
Published: April 2011

This study was undertaken to measure the effects of serotonin administration on local cerebral blood flow following blood–brain barrier (BBB) disruption with hypertonic urea. Rats were anesthetized with halothane in nitrous oxide and oxygen (70%:30%). In some animals urea (3.5 M) was infused retrogradely through an external carotid catheter, followed after 10 min by serotonin (50 ng kg−1 min−1) or physiological saline. Local cerebral blood flow was measured using the 14C-iodoantipyrine quantitative autoradiographic technique of Sakurada et al. (1978). The administration of saline or urea alone had only minimal effects on local cerebral blood flow. When the BBB was intact, serotonin produced a significant fall in regional blood flow only in the caudate nucleus. Following BBB disruption, however, serotonin produced a marked decrease in local perfusion in a number of discrete brain areas that are supplied by blood from the internal carotid artery. On the other hand, there were increases in local perfusion in areas not supplied by the internal carotid artery.
Comparison of Cerebrovascular Response to Hypoxic and Carbon Monoxide Hypoxia in Newborn and Adult Sheep
Authors: Koehler Raymond C. , Traystman Richard J. , Zeger Scott , Rogers Mark C. , Jones M. Douglas
Published: April 2011

Cerebral blood flow (CBF) responses to two types of isocapnic hypoxia, hypoxic hypoxia (HH) and carbon monoxide hypoxia (COH), were examined in seven unanesthetized adult sheep by the radiolabeled microsphere technique. Comparisons were made with newborn lambs (5–12 days old) previously studied under similar conditions. The arterial O2 content (Cao2) was reduced in a graded manner to 50–60% of the control value. During HH, CBF increased to maintain cerebral O2 delivery (Cao2 x CBF) in both adults and newborns; however, cerebral O2 uptake (CMRO2) did not change. Although CMRO2 was higher in newborns, the responses of CBF/CMRO2 to HH did not differ significantly in newborns and adults. In newborns, regional CBF showed that brainstem areas were particularly responsive to HH. In both age groups, CBF increased to a greater extent with COH than with HH for similar reductions in Cao2. This resulted in an increase in cerebral O2 delivery with COH. The degree to which COH differed from HH correlated with the magnitude of the leftward shift of the oxyhemoglobin dissociation curve that accompanies COH. In adults, CMRO2 fell by 16% with COH but was maintained in newborns. We conclude that maintenance of cerebral O2 delivery during acute, isocapnic HH is a property of CBF regulation common to both newborn and adult sheep. During COH, the position of the oxyhemoglobin dissociation curve is an additional factor that sets the level of O2 delivery. The fetal conditions of low Cao2 and a left-shifted oxyhemoglobin dissociation curve may have provided the newborn with a microcirculation better suited for maintaining CMRO2 during COH.
Iodoamphetamine as a New Tracer for Local Cerebral Blood Flow in the Rat: Comparison with Isopropyliodoamphetamine
Authors: Rapin Jean R. , Le Poncin-Lafitte Monique , Duterte Dominique , Rips Richard , Morier Elisabeth , Lassen Niels A.
Published: April 2011

Rats were injected with iodoamphetamine synthesized and labeled with 125I or with 125I-isopropyliodoamphetamine, a molecule of established value for the determination of local cerebral blood flow. The blood kinetics, tissue distribution, and brain uptake index for each tracer exhibited practically no differences. Autoradiographic quantification of the local cerebral blood flow, calculated according to the microsphere model, produced identical results for both molecules. However, compared with the values reported for other tracers, our values constituted an underestimation of white matter blood flow and a more real estimation of hippocampal flow. It is concluded from the brain uptake of the derivatives of both amphetamines during the first minutes following their injection that these tracers can be used as a chemical microembolus for the measurement of local cerebral blood flow.
A Noninvasive Approach to Quantitative Functional Brain Mapping with H215O and Positron Emission Tomography
Authors: Fox Peter T. , Mintun Mark A. , Raichle Marcus E. , Herscovitch Peter
Published: April 2011

Positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF) with intravenously administered 15O-labeled water and an adaptation of the Kety autoradiographic model are well suited to the study of functional-anatomical correlations within the human brain. This model requires arterial blood sampling to determine rCBF from the regional tissue radiotracer concentration ( Cr) recorded by the tomograph. Based upon the well-defined, nearly linear relation between Cr and rCBF inherent in the model, we have developed a method for estimating changes in rCBF from changes in Cr without calculating true rCBF and thus without arterial sampling. This study demonstrates that quantitative functional brain mapping does not require the determination of rCBF from Cr when regional neuronal activation is expressed as the change in rCBF from an initial, resting-state measurement. Patterned-flash visual stimulation was used to produce a wide range of increases in rCBF within the striate cortex. Changes in occipital rCBF were found to be accurately estimated directly from Cr over a series of 56 measurements on eight subjects. This adaptation of the PET/autoradiographic method serves to simplify its application and to make it more acceptable to the subject.
Effects of Bradykinin on Permeability and Diameter of Pial Vessels In vivo
Authors: Unterberg Andreas , Wahl Michael , Baethmann Alexander
Published: April 2011

The effect of bradykinin on the permeability and vasomotor response of pial vessels has been studied to enhance our understanding of the pathophysiological role of the kallikrein–kinin system in cerebral tissue. Intravital fluorescence microscopy of the pia arachnoidea was conducted using Na+-fluorescein, FITC-dextran, and FITC-albumin as low and high molecular weight blood–brain barrier indicators. Massive arterial dilatation evolved immediately upon administration of bradykinin by superfusion of the exposed cerebral surface. An increase of the arterial diameter by 40% was the maximal response found at bradykinin concentrations of 4 × 10−5 M. Arterial dilatation became attenuated with continuous superfusion of the preparation with bradykinin. In pial veins, a moderate reduction of the vessel diameter was observed, however, only after prolonged superfusion of the preparation. Bradykinin led to selective opening of the blood–brain barrier for Na+-fluorescein at super-fusate concentrations of ⩾4 × 10−7 M, but not for FITC-dextran or FITC-albumin. Topical administration of l-isoproterenol (10−4 M) was found to prevent extravasation of Na+-fluorescein in the presence of bradykinin concentrations of 4 × 10−6 M. Protection of the blood–brain barrier by isoproterenol was not observed when higher concentrations of bradykinin were employed. Intracarotid infusion of bradykinin led also to a selective opening of the blood–brain barrier for Na+-fluorescein, but not for FITC-dextran or FITC-albumin. In contrast to superfusion, this route of administration did not induce changes of the vasomotor behavior of the arteries or veins. Additional experiments with B1-agonists and -antagonists suggest that bradykinin causes the opening of the blood–brain barrier through an interaction with B2-receptors on endothelial cells, and arterial dilatation via interaction with B2-receptors on vascular smooth muscle cells. Our findings support the concept that the release of kinins in the brain during an acute cerebral lesion mediates secondary damaging processes by the enhancement of blood–brain barrier dysfunction.
Effect of Middle Cerebral Artery Compression on Pial Artery Pressure, Blood Flow, and Electrophysiological Function of Cerebral Cortex of Cat
Authors: Date H. , Hossmann K.-A. , Shima T.
Published: April 2011

In 20 cats, the left middle cerebral artery was gradually compressed with a microdriven vascular occluder implanted by a transorbital approach. Pial artery pressure, cortical blood flow, segmental vascular resistance, electrocorticogram, and cortical steady potentials were measured in the territory of the left middle cerebral artery and correlated with the degree of vascular stenosis. Pial artery pressure began to decrease when the lumen of the middle cerebral artery was reduced to 200 μm. Cortical blood flow and EEG power declined when pial artery pressure fell below 35–40 mm Hg; cortical steady potential started to shift toward negativity at a pressure below 25–30 mm Hg; and both hemodynamic and electrophysiological changes were maximal at a pressure below 10 mm Hg. When the vascular occlusion was released within 5 min after the onset of ischemia, a pial artery pressure of only 18 mm Hg was necessary to restore normal blood flow. After 1-h occlusion, normalization of flow occurred at a pressure of 30 mm Hg. Since this pressure is still substantially below normal pial artery pressure, no-reflow does not seem to be of significance in this experimental situation.
Effects of Cholecystokinin Octapeptide on Pial Arteriolar Diameter
Authors: McCulloch James , Kelly Paul A. T.
Published: April 2011

The effects of the perivascular microapplication of sulphated cholecystokinin octapeptide (CCK-8) on pial arteriolar calibre have been examined in anaesthetised cats using a video-display image-splitting technique. The microinjection of CCK-8 (10−10–10−6 M) did not alter significantly the calibre of the pial arterioles. The presence of CCK-8 (10−7 M) in the injectate did not modify the constriction or dilatation of pial arterioles provoked by the perivascular microinjection of alkalotic (pH 7.45) or acidic (pH 6.8) artificial CSFs, respectively. Thus, although CCK-8-immunoreactive neuronal processes are known to be associated with cortical blood vessels, CCK-8 appears to have minimal vasomotor effects on pial vessels.
Quantification of Glucose Utilization in an Experimental Brain Tumor Model by the Deoxyglucose Method
Authors: Kato Amami , Diksic Mirko , Yamamoto Y. Lucas , Feindel William
Published: April 2011

Reevaluation of lumped and rate constants is necessary when Sokoloff's 2-deoxyglucose (DG) method is used to measure glucose utilization in pathological tissue. We describe here a modification of Sokoloff's lumped constant measurement that permits simultaneous estimation of both lumped and rate constants from a single animal experiment. A subcutaneous tumor model (AA ascites tumor) was used for measurement of these constants with a procedure similar to Sokoloff's that kept the plasma tracer concentration constant. Measured constants were as follows: lumped constant, 0.654 ± 0.081; k*1, 0.196 ± 0.038 min−1; k*2, 0.262 ± 0.067 min−1; k*3, 0.117 ± 0.044 min−1. These constants were used to quantify glucose utilization in the implanted brain tumor. To test the validity of this method, we compared a fraction of the free DG pool calculated using the tumor constants with a fraction measured directly by chromatographic analysis of tissue samples from both subcutaneous tumor and implanted brain tumor. The values derived by chemical analysis agreed well with those predicted by the calculations. The value of k*4 varied from 0.0031 ± 0.0018 min−1 for the tumor tissue to 0.0214 ± 0.0024 min−1 for tumors with a large necrotic center. This method would be especially useful when applied to xenograft human gliomas in nude mice for quantification of glucose utilization in human gliomas by means of positron emission tomography.
Glucose Metabolic Rate Kinetic Model Parameter Determination in Humans: The Lumped Constants and Rate Constants for [18F]Fluorodeoxyglucose and [11C]Deoxyglucose
Authors: Reivich M. , Alavi A. , Wolf A. , Fowler J. , Russell J. , Arnett C. , MacGregor R. R. , Shiue C. Y. , Atkins H. , Anand A. , Dann R. , Greenberg J. H.
Published: April 2011

The rate constants and lumped constants (LCs) for [18F]fluorodeoxyglucose ([18F]FDG) and [11C]deoxyglucose ([11C]DG) were determined in humans for the glucose metabolic rate kinetic model used to measure local cerebral glucose consumption. The mean values (±SE) of the LCs for [18F]FDG and [11C]DG are 0.52 ± 0.028 (n = 9) and 0.56 ± 0.043 (n = 6), respectively. The mean values (±SE) of the rate constants k*1, k*2, k*3, and k*4 for [18F]FDG for gray matter are 0.095 ± 0.005, 0.125 ± 0.002, 0.069 ± 0.002, and 0.0055 ± 0.0003, respectively. The corresponding values for white matter are 0.065 ± 0.005, 0.126 ± 0.003, 0.066 ± 0.002, and 0.0054 ± 0.0006, respectively. Using these values and previously published values for the rate constants for [11C]DG, the average whole-brain metabolic rates for glucose in normal subjects measured with [18F]FDG and [11C]DG are 5.66 ± 0.37 (n = 6) and 4.99 ± 0.23 (n = 6) mg/100 g/min, respectively. These values are not significantly different ( t = 1.56, p > 0.10) and agree well with reported values in the literature determined by means of the Kety-Schmidt technique.
Regional Cerebral Blood Volume and Hematocrit Measured in Normal Human Volunteers by Single-Photon Emission Computed Tomography
Authors: Sakai Fumihiko , Nakazawa Keiji , Tazaki Yoshiaki , Ishii Katsumi , Hino Hidetada , Igarashi Hisaka , Kanda Tadashi
Published: April 2011

Single-photon emission computed tomography (SPECT) was used for the measurement of regional cerebral blood volume (CBV) and hematocrit (Hct) in normal healthy human volunteers (mean age 30 ± 8 years). Regional cerebral red blood cell (RBC) volume and plasma volume were determined separately and their responses to carbon dioxide were investigated. Ten right-handed healthy volunteers were the subjects studied. SPECT scans were performed following intravenous injection of the RBC tracer (99mTc-labeled RBC) and plasma tracer (99mTc-labeled human serum albumin) with an interval of 48 h. Regional cerebral Hct was calculated as the regional ratio between RBC and plasma volumes and then was used for calculating CBV. Mean regional CBV in the resting state was 4.81 ± 0.37 ml/100 g brain, significantly greater in the left hemisphere compared with the right by 3.8% (p < 0.01). Mean regional RBC volumes (1.50 ± 0.09 ml/100 g brain) were less than mean regional plasma volumes (3.34 ± 0.28 ml/100 g brain), and mean regional cerebral Hcts were 31.3 ± 1.8%, which was 75.9 ± 2.1% of the large-vessel Hct. During 5% CO2 inhalation, increases in plasma volume (2.48 ± 0.82%/mmHg Paco2) were significantly greater than for RBC volume (1.46 ± 0.48%/mmHg Paco2). Consequently, the cerebral-to-large-vessel Hct ratio was reduced to 72.4 ± 2.2%. Results emphasize the importance of cerebral Hct for the measurement of CBV and indicate that regional cerebral Hcts are not constant when shifted from one physiological state to another.
Regional Cerebrovascular Transport of Leucine as Measured by the in situ Brain Perfusion Technique
Authors: Smith Quentin R. , Takasato Yoshio , Sweeney Daniel J. , Rapoport Stanley I.
Published: April 2011

Leucine influx into six brain regions was determined in anesthetized rats with the in situ brain perfusion technique using either saline or plasma perfusate. This technique has several advantages over other methods such as the brain uptake index (BUI) technique. The concentration dependence of l-leucine influx was best described by a model with a saturable and a nonsaturable component. For the saturable component, Vmax equaled 10.67 ± 0.21 × 10−4 μmol s−1 g−1 and Km equaled 0.0257 ± 0.0009 μmol ml−1, whereas the constant of nonsaturable diffusion ( Kd) equaled 0.957 ± 0.067 × 10−4 s−1 in the parietal lobe during saline perfusion. Vmax was higher in the cortical lobes than in other brain areas, probably owing to a greater capillary surface area. There were no regional differences in Km or Kd. The apparent Km for l-leucine during plasma perfusion was 20 times greater than the Km during saline perfusion, and 3 to 4 times greater than the plasma leucine concentration, owing to competitive inhibition of leucine transport by other large neutral amino acids in plasma. These results for Vmax, Km, and Kd differ by three- to fourfold from previous estimates obtained with the BUI technique. The high apparent Km during plasma perfusion indicates that leucine influx is a linear function of plasma concentration up to 0.5 μmol ml−1 when the plasma concentrations of other amino acids remain constant, whereas influx would be approximately constant when plasma concentrations of all large neutral amino acids increased or decreased by a constant fraction.
Two-Day Starvation Does Not Alter the Kinetics of Blood-Brain Barrier Transport and Phosphorylation of Glucose in Rat Brain
Authors: Crane Paul D. , Pardridge William M. , Braun Leon D. , Oldendorf William H.
Published: April 2011

The blood-brain barrier (BBB) transport and brain phosphorylation of glucose were assessed in conscious rats subjected to 2 days of starvation. Although plasma glucose decreased, no significant changes in brain blood flow, BBB glucose transport, or 2-deoxy-d-glucose phosphorylation were observed. The data suggest that adaptive changes of brain glucose metabolism previously observed in starvation are located beyond the initial steps of brain entry and phosphorylation.
Cerebral Ischemia in Rabbit: A New Experimental Model with Immunohistochemical Investigation
Authors: Yamamoto Kazumi , Yoshimine Toshiki , Yanagihara Takehiko
Published: April 2011

Regional cerebral ischemia was produced in the rabbit by unilateral transorbital occlusion of the middle cerebral artery (procedure I); the middle cerebral and azygos anterior cerebral or anterior communicating artery (procedure II); or the middle cerebral, azygos anterior cerebral or anterior communicating, and internal carotid artery (procedure III). Evolution of ischemic lesions was examined with the immunohistochemical reaction for tubulin. With procedure I, ischemic lesions did not become constantly visible for 6 h in the basal ganglia and for 8 h in the frontoparietal region of the cerebral cortex. With procedure II, it was shortened to 3 h in the basal ganglia and to 6 h in the cerebral cortex. With procedure III, the ischemic lesions were observed in 1 h both in the basal ganglia and in the cerebral cortex as loss of the reaction for tubulin in the neuropil, nerve cell bodies, and dendrites. The evidence of neuronal damage became apparent in the same areas later by staining with hematoxylin–eosin. The experimental model presented here may be suitable for investigation of the mechanism that shifts reversible ischemia to cerebral infarction and for evaluation of the effectiveness of pharmacological intervention.