bluuebunny/crossref_metadata_2025 huggingface dataset:
The Value of Upsloping ST Depression in Diagnosing Myocardial Ischemia
Authors: Polizos George , Ellestad Myrvin H.
Published: July 2006

We evaluated the value of upsloping ST‐segment depression in predicting the severity of myocardial ischemia. Comparison of the exercise electrocardiographic changes was made to myocardial perfusion images and coronary angiograms as the criteria for ischemia. We retrospectively reviewed 621 patients who underwent exercise technetium‐99m tetrofosmin single photon emission computed tomography (SPECT) for the assessment of suspected or known coronary artery disease followed by coronary angiography within a 3‐month period. The test sensitivity and specificity of 1 mm horizontal or downsloping ST depression in predicting reversible ischemia as assessed by gated SPECT imaging (GSI) were 65% and 87%, respectively. The corresponding values were 67% and 94% compared to coronary angiography. The sensitivity and specificity of gated SPECT imaging compared to coronary angiography were 78% and 89%. On the other hand when 1 mm upsloping ST depression at 70 ms past the J‐point was regarded as abnormal, along with horizontal and downsloping, the sensitivity and specificity were 82% and 90% compared to myocardial perfusion imaging, and 77% and 92% as assessed by coronary angiography. We conclude that upsloping ST‐segment depression is associated with an increased risk of coronary artery disease and is a valuable predictor of myocardial ischemia.
An investigation of the viscoelastic properties of the periodontium in monkeys
Authors: Wills D. J. , Picton D. C. A. , Davies W. I. R.
Published: July 2006

The non‐linear response of the tooth to external stresses is due to the interaction of the fibrous, cellular and vascular elements of the supportive tissues. In this study the relaxation of the central incisors after the suden removal of axial forces of 2.5 Newton was investigated in three monkeys. The displacement‐time curve was analysed using a technique of exponential curve fitting. Analysis shows that the periodontium is viscoelastic in nature and may be represented by three and possibly five Voigt elements. Comparison of the upper and lower incisors indicate that while the same basic processes are active in both mandible and maxilla they are different in magnitude. In the case of the fastest acting Voigt element the response is more rapid for lower teeth than for upper ones, corresponding either to less damping or a stronger spring constant. This difference in magnitude is presumably due either to differences in the architecture of the periodontium and alveolar bone or to the local blood supply. The authors are indebted to Dr. M. Braden of the London Hospital Medical College for his advice and guidance. Thanks are due also to members of the Department of Medical Physics of the University College Hospital, particularly Mr. J. S. Clifton for his encouragement, Mr. M. Conway and Mr. R. Favre for the construction of the force applicator and Mr. K. J. Cassell for his assistance.
Monitoring periodontal disease status in smokers and nonsmokers using a gingival crevicular fluid matrix metalloproteinase‐8‐specific chair‐side test
Authors: Mäntylä P. , Stenman M. , Kinane D. , Salo T. , Suomalainen K. , Tikanoja S. , Sorsa T.
Published: July 2006

Background and Objective:  With current periodontal diagnostic tools it is difficult to identify susceptible individuals or sites at risk. The aim of this study was to evaluate the efficacy of the matrix metalloproteinase (MMP)‐8‐specific chair‐side dip‐stick test in longitudinally monitoring the periodontal status of smoking (S) and nonsmoking (NS) patients with chronic periodontitis, using their gingival crevicular fluid (GCF) MMP‐8 concentrations.

Material and Methods:  Clinical parameters, MMP‐8 test results and concentrations were monitored in 16 patients after initial treatment and in 15 patients after scaling and root planing (SRP), every other month, over a 12‐mo time period. Progressing and stable sites, and sites with exceptionally high MMP‐8 concentrations, were analysed in smokers and nonsmokers.

Results:  SRP reduced the mean GCF MMP‐8 levels, test scores, probing depth (PD), attachment loss (AL) and bleeding on probing (BOP). In sites of periodontal disease progression, the distribution of MMP‐8 concentrations was broader than in stable sites, indicating a tendency for elevated concentrations in patients with periodontal disease. The mean MMP‐8 concentrations in smokers were lower than in nonsmokers, but in smokers' and nonsmokers' sites with progressive disease, MMP‐8 concentrations were similar. Sites with exceptionally elevated MMP‐8 concentrations were clustered in smokers who also showed a poor response to SRP. In these sites, the MMP‐8 concentration did not decrease with SRP and these sites were easily identified by the MMP‐8 test.

Conclusion:  Persistently elevated GCF MMP‐8 concentrations may indicate sites at risk, as well as patients with poor response to conventional periodontal treatment (e.g. SRP). MMP‐8 testing may be useful as an adjunct to traditional periodontal diagnostic methods during the maintenance phase.
Deoxyribonuclease I footprinting reveals different DNA binding modes of bifunctional platinum complexes
Authors: Chválová Kateřina , Kašpárková Jana , Farrell Nicholas , Brabec Viktor
Published: July 2006

Deoxyribonuclease I (DNase I) footprinting methodology was used to analyze oligodeoxyribonucleotide duplexes containing unique and single, site‐specific adducts of trinuclear bifunctional platinum compound, [{trans‐PtCl(NH3)2}2μ‐trans‐Pt(NH3)2{H2N(CH2)6NH2}2]4+ (BBR3464) and the results were compared with DNase I footprints of some adducts of conventional mononuclear cis‐diamminedichloroplatinum(II) (cisplatin). These examinations took into account the fact that the local conformation of the DNA at the sites of the contacts of DNase I with DNA phosphates, such as the minor groove width and depth, sequence‐dependent flexibility and bendability of the double helix, are important determinants of sequence‐dependent binding to and cutting of DNA by DNase I. It was shown that various conformational perturbations induced by platinum binding in the major groove translated into the minor groove, allowing their detection by DNase I probing. The results also demonstrate the very high sensitivity of DNase I to DNA conformational alterations induced by platinum complexes so that the platinum adducts which induce specific local conformational alterations in DNA are differently recognized by DNase I.
Hydrogeologic Programme of the Geological Survey of Canadaa
Authors: Brandon L. V.
Published: July 2006

The Hydrogeologic Programme of the Geological Survey of Canada includes: 1) Research into the science of hydrogeology which requires water balance studies of selected “Type Basins.” 2) The production of Water Probability Maps to indicate the location of ground‐water resources. 3) Studies to improve various techniques for ground‐water development. Ground‐water investigations are also carried out by various Provincial organizations.
Optimum Depth of Wells in Crystalline Rocksa
Authors: Davis S. N. , Turk L. J.
Published: July 2006

Water‐bearing properties of crystalline rocks are dependent on the occurrence of joints and faults and the extent of weathering. Interstitial openings caused by weathering are mostly at depths of less than 100 feet. Joints are less abundant and openings along joint planes are smaller as depth increases. Openings along fault surfaces also tend to close with depth. These geological observations which indicate a decrease in rock permeability with depth are verified by a study of well yields and water‐injection tests. Mean yields per foot of well are 0.23 to 0.30 gpm at 100 feet but only 0.013 to 0.04 gpm at 1000 feet. Mean injection rates per foot of drill hole under 100 psi pressure are 0.11 to 0.4 gpm at 100 feet but only 0.014 to 0.038 gpm at 1000 feet. Median values of both well yields and injection rates are from one‐half to one‐third of the mean values. Geologic structure is more important than rock type in determining yields and injection rates. The decrease in rock permeability with depth indicates an increase in the unit cost of water with depth. The optimum depth of a well is, therefore, determined largely by economic factors. Unless geologic factors are favorable, wells in crystalline rocks should be less than 600 feet deep. In general, domestic wells should be less than 150 to 250 feet deep.
Ground‐Water Exploration in Spain
Authors: Pemberton R. H.
Published: July 2006

As part of a Four Year Development Program, the government of Spain is tackling the problem of aridity. Its plans include agricultural, economic and social improvements in many of the country's arid areas. Basic to these improvements is a plan developed to study the ground‐water possibilities of about half of Spain. The study, to be completed in 1967, will result in hydrogeologic maps showing the ground‐water potential of arid areas. If sufficient ground‐water reserves are found, agriculture, tourism and migration from arid areas can all be aided by this program.
Hydrologic Significance of Tectonic Fractures Detectable on Airphotos
Authors: Setzer Jose
Published: July 2006

Photogeologic study has been useful in the location of ground‐water sources in the state of Sao Paulo, Brazil, and could be important to the investigation of water resources in other areas.

Until 1963, it was believed that large areas of the state were unsuited for the location of ground‐water wells (as in pre‐Devonian crystalline formations) and others weregenerally considered too hazardous (Paleozoic and Tertiary: sandstone lenses in shales). Since that time, when aerial photographs of the whole state became available, the authorhas verified an earlier hypothesis of his own that there are actually very few areas in the state which do not have suitable locations for water wells, and that photogeology is a most valuable method of prospecting.

The water sources are parts of highly developed fault/ fracture systems which are identifiable on aerial photo‐graphs, at least in this warm humid climate with dry season. Over the fractures the rocks are deeply decomposed, the debris are removed in the rainy season, and existence of water in the dry season promotes higher and denser vegeta‐tion along aquiferous fractures, which usually are located in deep straight‐line valleys. Even where competent beds are overlain by more than 100 m of unconsolidated strata, many discontinuous nets of parallel straight‐line segments are detectable probably because all fractures are really faults with significant throw.

To be most effective, the method requires stereoscopic study of areas having dimensions on the order of 10 × 10 km. The selection of locations for drilling should be sup‐ported by analyses of the dip of fracture planes (hade) and by other geological‐geophysical methods, especially by subsoil electrical resistivity surveying.
New Approaches to Water‐Resources Investigations in Upstate New Yorkaa
Authors: La Sala A. M.
Published: July 2006

The scope of area1 investigations of water resources in New York has changed within the last 4 years. Prior 1962, most investigations covered only counties or smaller areas and were mainly restricted to ground‐water resources Since 1762, investigarions have covered largebasin (2,000‐4,000 square miles) with the purpose of defining total water resources so that basin‐wldc comprehensive plans for water development can be prepared.

Ground water has been intensively studied in the basin investigations, both because of its large potential for future development, and becaus e of it sinterre lation with the surface‐water resources. The latter reason is particularly important because the principal aquifers are numerous u nconnect edglacials and andgravel deposits that are crossed by streams. This ground‐water regimen to a large degree determines the flow characteristics and water quality of streams. Conversely, streamflow data provide acon‐venient means of assessing ground‐water availability.Some approaches used in basin studies are:

(1)(1) numerous quantitative and qualitative observations of low streamflow to define the principal areas of ground‐water discharge and to define the quantity and quality of discharging ground water

(2)estimation of total ground‐water dischar gepas stream gages from daily streamflow records by correlation with ground‐water levels and by analysis of the records

(3) assessment of recharge to particular sand and gravel deposit swith inbroadlimits, using the data on ground‐water discharge to streams

(4) estimation of a daily chemical quality hydrograph on the basis of quantity and quality of both ground‐water discharge and overland runoff
The Relationship Between Specific Capacity and Aquifer Transmissibility in the Houston Area, Texas
Authors: Gabrysch R. K.
Published: July 2006

Water well drillers gather information essential to recovery tests as part of normal procedure. Added effort could yield additional valuable information. More care in measurement of water levels both before and after a period of pumping can be used with ground‐water formulae to determine approximate well efficiency.

A relationship exists between the ability of an aquifer to perform (transmissibility) and the specific capacity of a well. By means of pumping tests, both transmissibility and specific capacity may be measured. The theoretical specific capacity can be obtained based on the measured transmissibility. Well efficiency may be estimated from a comparison between measured specific capacity and theoretical specific capacity.

Tests of wells owned by the City of Houston, Texas, were selected for analysis. Test results were compared with curves showing theoretical relationships. From the comparison, wells in the Houston area are not completely developed. It may not be economical to develop a well to 100 percent efficiency, but theoretical relationships should be used in well development.
Hydrogeology of Desert Basinsa
Authors: Maxey George B.
Published: July 2006

Hydrologic systems in arid lands normally include a recharge area in mountains and a discharge area in lowlands often with an intermediate area of lateral flow between recharge and discharge areas. This system is often modified by local geologic, climatic, and physiographic factors. Most water‐supply, contamination and disposal problems arise from a combination of features superimposed on this system by concentration of population and agricultural activity in the discharge areas. Also most of our data on the system comes from the lowlands and little data is available from the recharge areas.

In the Great Basin two general categories of ground‐water flow systems are recognized: (1) local flow systems where drainage areas are usually small, flow paths are relatively short, interbasin flow is uncommon, springs have large fluctuations in discharge, water temperature is low, and concentration of Na, K, Cl, and SO4 is low, and (2) regional flow systems, where drainage areas are large, flow paths long, interbasin flow common, springs have large discharge, and the water is characteristically of higher temperature and contains higher concentrations of K, Na, Cl, and SO4. Hydrologic approaches used, in addition to conventional methods, include hydrologic budget, water‐potential, and water‐chemistry studies. Although detailed delineation of most flow systems in Nevada has not been accomplished, integration of hydrologic, geologic, and chemical methods allow approximate portrayal of many systems, both local and regional.

Adequate methods upon which to base planning for optimum development of water resources in desert basins are now available. A conceptual model of optimal ground‐water reservoir development illustrates how to determine optimum use of storage and perennial yield provided the use to which the water is to be put and the time of withdrawal are known.
Geophysical Surveys in the Vicinity of Sanitary Landfills in Northeastern Illinoisa
Authors: Cartwright Keros , McComas Murray R.
Published: July 2006

Electrical earth resistivity and soil temperature surveys have been conducted in the vicinity of four sanitary landfills in northeastern Illinois to test the possibility of detecting and tracing any chemical or temperature alteration of ground water by leachates from buried refuse. Reference data on water quality, levels, and movement were provided by a system of monitor wells drilled for a hydrogeologic study of the landfills.

The resistivity survey, which was in homogeneous silty sand outwash, traced mineralized water from the landfill for a distance of more than 1000 feet. Apparent resistivity values were one fourth those obtained from unaffected areas. Interpretations of direction of ground‐water flow and location of discharge boundaries from the geophysical data agree vith interpretations based on the monitor well data.

The soil temperature survey indicated the presence of a halo of higher temperatures around the landfill and indicated areas of surface recharge.

The geophysical surveys show, in general, that chemically altered water is traceable in uniform earth materials where the depth of the water table is constant.
Statistical Evaluation of Salinity and Nitrate Content and Trends Beneath Urban and Agricultural Areas — Fresno, California
Authors: Nightingale Harry I.
Published: July 2006

The salinity and nitrate content of well water for an urban zone (Fresno‐Clovis, California) and the immediate surrounding irrigated agricultural zone were compared using data for 1950 through 1967. Time trends in these water chemical properties were evaluated statistically by dividing the 18‐year period into three 6‐year periods. Salinity of the urban zone ground water has increased with time, whereas that of the agricultural zone has fluctuated considerably. Possible reasons for changes are discussed. The nitrate content of well water from both zones has increased with time, with water from the agricultural zone showing the greatest increase. Key words; ground‐water degradation; salinity; nitrate.
On the Design and Construction of Infiltration Galleries
Authors: Bennett Truman W.
Published: July 2006

Reliable prediction of the yield of infiltration galleries can be made only on the basis of careful field testing combined with evaluation of surface flow‐duration data. While extensive pump testing is often relatively expensive the information obtained indicates the long‐term utility of the system. Pump test procedures and methods of analysis are outlined.

With proper design much wider utilization can be made of infiltration galleries than is presently done. The long life and low maintenance requirements are particularly favorable for small systems. Design and maintenance suggestions are made for successful operations.
The Significance of Percolation Water in Limestone Catchments
Authors: Drew David P.
Published: July 2006

Studies of limestone hydrology have largely ignored the possible significance of water not flowing in major conduits. This component is designated “percolation water.” The importance of percolation water in an area is probably a function of rock type, structure and hydrologic characteristics. Experiments undertaken in England and Jamaica tracing percolation water with the dyestuff Pyranine Conc. suggest longer flow‐through times than for water sinking at discrete points on the surface (allogenic water). The soil cover in an area may be in part responsible for this delay. Results from percolation water traces may be used to compile isochronal maps of limestone catchments.
Field Study of Subsurface Spent Sulfite Liquor Movement Using Earth Resistivity Measurements
Authors: Hackbarth Douglas A.
Published: July 2006

A new method is presented for supplementing data from piezometers to monitor waste disposal sites. This method involves examination of a time sequence of resistivity measurements at fixed points in a disposal area.

Spent sulfite liquor moving away from a seepage pit was traced by examining a grid of earth resistivity measurements made before and after dumping had taken place. The method appears to provide results which correlate with specific conductivity of water samples from piezometers provided the following conditions are met:

Highly conductive contaminant moving at shallow depth.

Water table close to surface.

Uniform soil and vegetative conditions.

Proper selection of electrode spacings.
Practical Corrosion and Incrustation Guide Lines for Water Wells
Authors: Mogg Joe L.
Published: July 2006

Corrosion and incrustation of water wells is defined and classified into groups which fit most field problems. Case histories with concomitant water analyses are described. A readily determined index for the magnitude of corrosion is presented along with recommended materials to correspond with the indices. The theory for the most common well incrustants is presented. Recommendations are made for minimizing the rate of incrustation in wells supplying water known to be incrusting and thus eventually clogging well screens. Treatments for incrusted wells are described including iron bacteria. A ten‐year case history of iron bacteria fouling is presented. Nonmetallics are discussed.

Descriptors: Well failures, corrosion of well components, incrustation of screens, water analyses, index, guide lines, nonmetallics, iron bacteria.

Identifiers: Corrosion and incrustation problems in wells.
Theory of Ground‐Water Recharge for a Strip Basin
Authors: Amar Abnish C.
Published: July 2006

Formulation and solution of one‐dimensional analytical and computational models, linear as well as nonlinear, pertaining to a typical ground‐water recharge pattern are presented. The objective of this investigation is to direct attention toward an evaluation and correlation of the various theoretical models based on the Dupuit‐Forchheimer (D‐F) approximations for the unsteady hydrodynamic behavior of the proposed recharge system under saturated flow conditions. Comparisons with the pertinent experimental data, presented in the form of dimensionless graphs, indicate that the linear D‐F theory is valid for relatively small water‐table rises but for large rises it predicts substantially greater rises than actually occur, particularly beneath and in the vicinity of the recharge basin. The range of validity is considerably improved between theory and experiments for relatively large rises using the nonlinear theory.
Step‐Drawdown Test Analysis by Computer
Authors: Labadie John W. , Helweg Otto J.
Published: July 2006

Many geohydrologists believe that the step‐drawdown test is useful in determining many important characteristics of a well, whereas others altogether question its utility. In addition to this controversy, its application is hindered because the graphical analysis of data is unwieldy. A computer code is presented for step‐drawdown test analysis which is efficient and simple to use; moreover, it is an example of how optimization can be used in a practical way. A listing of the FORTRAN code is included along with some example calculations.
Ground‐Water Turbidity Resulting from Artificial Recharge
Authors: Nightingale Harry I. , Bianchi William C.
Published: July 2006

Turbid ground water is rarely observed in domestic or public supply aquifers. At the Leaky Acres Recharge Facility at Fresno, California, water of low salinity (<50 μmhos/cm) and turbidity (<5 FTU, Formazin turbidity units) is recharged in the spreading basins. Six months after the start of the third (1973) recharge period, the ground‐water salinity was decreased to about 100 μhos/cm from the initial mean of 147 μhos/cm and the ground water became visibly turbid (>5 FTU). Two months later, some peripheral domestic wells also began to become turbid. After two more recharge periods (1974 and 1975), turbidity at 10 observation wells beneath Leaky Acres averaged 18 FTU and salinity averaged 74/μmhos/cm. By this time, ground‐water turbidity in peripheral wells near Leaky Acres had decreased to <0.5 FTU. This turbidity was traced to poorly‐crystallized and extremely fine colloids, which have leached from the surface soils because of the low salinity of the recharge water. Laboratory and field studies showed that gypsum application will reverse the phenomena, but such treatment is uneconomical. This phenomenon is a transient one, and now turbidity outside the recharge area is insignificant from a water quality viewpoint. However, the magnitude of the mass of material in transit through the profile if stabilized through flocculation or sieving in soil pore space, could greatly change the water transmission and so recharge project performance. However, we have not yet noted this effect at Leaky Acres.
INTERNATIONAL LESSONS FOR THE PROPERTY PRICE BOOM IN SOUTH AFRICA
Authors: Funke Norbert , Kißmer Friedrich , Wagner Helmut
Published: July 2006

South Africa appears to share some of the characteristics (property price boom, easing of monetary policy, strong domestic demand growth) of asset price booms in industrial countries that were followed by a period of weak growth. The international experience suggests that a number of practical obstacles need to be overcome before a more proactive role for monetary policy is warranted. However, a larger variety of available mortgage contracts, including longer‐term fixed‐rate contracts, should allow for a more efficient allocation of interest rate risks. Also, a more systematic nationwide collection of property price data, including data on commercial property price developments, would provide a more representative basis for analysis.
Flank Wear Progression During Machining Metal Matrix Composites
Authors: Kannan S. , Kishawy H. A. , Balazinski M.
Published: July 2006

The machining of composites present a significant challenge to the industry. The abrasive reinforcements cause rapid tool wear and increases the machining cost. The results from machining metal matrix composites (MMCs) with conventional tools show that the main mechanism of tool wear includes two-body abrasion and three-body abrasion. A more flexible method that can be considered as a cost-saving technique is therefore sought for studying the machinability characteristics of these materials. In the previous paper, a methodology for predicting the tool flank wear progression during bar turning of MMCs was presented (Kishawy, Kannan, and Balazinski, Ann. CIRP, 54/1, pp. 55–59). In the proposed model, the wear volume due to two-body and three-body abrasion mechanisms was formulated. Then, the flank wear rate was quantified by considering the tool geometry in three-dimensional (3D) turning. Our main objective in this paper is to validate the proposed model by conducting extensive bar turning experiments under a wide range of cutting conditions, tool geometries, and composite material compositions. The cutting test results showed good agreement between predicted and measured tool wear progression.
The Geometry of Musical Chords
Authors: Tymoczko Dmitri
Published: July 2006

A musical chord can be represented as a point in a geometrical space called an orbifold. Line segments represent mappings from the notes of one chord to those of another. Composers in a wide range of styles have exploited the non-Euclidean geometry of these spaces, typically by using short line segments between structurally similar chords. Such line segments exist only when chords are nearly symmetrical under translation, reflection, or permutation. Paradigmatically consonant and dissonant chords possess different near-symmetries and suggest different musical uses.
A High-Brightness Source of Narrowband, Identical-Photon Pairs
Authors: Thompson James K. , Simon Jonathan , Loh Huanqian , Vuletić Vladan
Published: July 2006

We generated narrowband pairs of nearly identical photons at a rate of 5 × 10
4
pairs per second from a laser-cooled atomic ensemble inside an optical cavity. A two-photon interference experiment demonstrated that the photons could be made 90% indistinguishable, a key requirement for quantum information-processing protocols. Used as a conditional single-photon source, the system operated near the fundamental limits on recovery efficiency (57%), Fourier transform–limited bandwidth, and pair-generation-rate–limited suppression of two-photon events (factor of 33 below the Poisson limit). Each photon had a spectral width of 1.1 megahertz, ideal for interacting with atomic ensembles that form the basis of proposed quantum memories and logic.
Best practice in primary care pathology: review 6: Figure 1
Authors: Smellie W S A , Forth J , Coleman J J , Irvine W , Dore P C , Handley G , Williams D G , Galloway P J , Kerr K G , Herriot R , Spickett G P , Reynolds T M
Published: July 2006

This sixth best practice review examines four series of common primary care questions in laboratory medicine: (1) laboratory monitoring in hypertension and heart failure abnormalities; (2) markers of inflammatory joint disease; (3) laboratory investigation of chronic diarrhoea; and (4) mumps and chickenpox. The review is presented in question–answer format, referenced for each question series. The recommendations represent a precis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus based rather than evidence based. They will be updated periodically to take account of new information.
Bicalutamide 50 mg monotherapy in patients with isolated high-grade PIN: findings in repeat biopsies at 6 months
Authors: Bono Aldo V , Mazzucchelli Roberta , Ferrari Ilaria , Lopez-Beltran Antonio , Galosi Andrea B , Cheng Liang , Montironi Rodolfo
Published: July 2006

Objectives:To evaluate morphological findings in repeat biopsies in patients with isolated high-grade prostatic intraepithelial neoplasia (HGPIN) after a 6-month course of bicalutamide (Casodex) 50 mg/day.

Methods:20 consecutive patients with isolated HGPIN in prostate biopsies were treated for 6 months with bicalutamide 50 mg/day. After treatment, the patients were resubmitted to prostate biopsy mapping. The control group included 22 untreated consecutive patients with isolated high-grade PIN with repeat biopsies taken 6 months after the initial biopsies.

Results:In the initial biopsies of the treated group, HGPIN was monofocal in 12 patients and plurifocal in 8. In the repeat biopsies HGPIN was present in 2 patients, monofocal in both, whereas prostate adenocarcinoma (PCa) was discovered in one. In the control group, HGPIN was monofocal in 15 and plurifocal in 7. In the repeat biopsies HGPIN was present in six patients, being monofocal in three and plurifocal in the other three. PCa was present in one.

Conclusions:There was a lower incidence of HGPIN (treated group vs control: 10% vs 27.2%) after 6 months of bicalutamide. Reduction in its extent was also observed (treated group vs control: monofocal 100% vs 50%). Treatment did not affect the incidence of cancer (treated vs control: 5% vs 4.5%).
Treatment of inflammatory myopathies
Authors: Cordeiro A C , Isenberg D A
Published: July 2006

Idiopathic inflammatory myopathies, notably polymyositis and dermatomyositis are comparatively uncommon diseases and few randomised, double blind placebo controlled trials have been done. Final validation of measures to assess outcome and response to treatment is awaited. Corticosteroids are an effective initial treatment, although rarely tested in randomised controlled trials. Unfortunately, not all patients respond to them and many develop undesirable side effects. There is thus a need for second line agents notably immunosuppressives or intravenous immunoglobulin. There are no defined guidelines or best treatment protocols agreed internationally and so the medical approach must be individualised, based on the severity of clinical presentation, disease duration, presence of extramuscular features, and prior therapy and contraindications to particular agents. There is still a significant percentage of non-responders (around 25%) and clinical relapses. Novel therapeutic approaches are now directed towards cytokine modulation and the use of monoclonal antibodies targeting B and T cells.
Obesity in childhood and adolescence: evidence based clinical and public health perspectives
Authors: Reilly J J
Published: July 2006

A global epidemic of paediatric obesity occurred in recent years, and prevalence of obesity is continuing to rise. In the developed world obesity is now the most common disease of childhood and adolescence. Paediatric obesity is not a cosmetic issue, being associated with a significant burden of ill health both for obese children and for adults who were obese as children. Health professionals tend to underestimate the impact of paediatric obesity, and lack the skills, knowledge, and time to treat it effectively. This short review aims to summarise recent systematic reviews on the origins, consequences, prevention, and treatment of paediatric obesity.
The Anthropology of Money
Authors: Maurer Bill
Published: July 2006

This review surveys anthropological and other social research on money and finance. It emphasizes money's social roles and meanings as well as its pragmatics in different modalities of exchange and circulation. It reviews scholarly emphasis on modern money's distinctive qualities of commensuration, abstraction, quantification, and reification. It also addresses recent work that seeks to understand the social, semiotic, and performative dimensions of finance. Although anthropology has contributed finely grained, historicized accounts of the impact of modern money, it too often repeats the same story of the “great transformation” from socially embedded to disembedded and abstracted economic forms. This review speculates about why money's fictions continue to surprise.
Obesity in Biocultural Perspective
Authors: Ulijaszek Stanley J. , Lofink Hayley
Published: July 2006

Obesity is new in human evolutionary history, having become possible at the population level with increased food security. Across the past 60 years, social, economic, and technological changes have altered patterns of life almost everywhere on Earth. In tandem, changes in diet and physical activity patterns have been central to the emergence of obesity among many of the world's populations, including the developing world. Increasing global rates of obesity are broadly attributed to environments that are obesogenic, against an evolutionary heritage that is maladaptive in these new contexts. Obesity has been studied using genetic, physiological, psychological, behavioral, cultural, environmental, and economic frameworks. Although most obesity research is firmly embedded within disciplinary boundaries, some convergence between genetics, physiology, and eating behavior has taken place recently. This chapter reviews changing patterns and understandings of obesity from these diverse perspectives.
Distinct role of Rab3A and Rab3B in secretory activity of rat melanotrophs
Authors: Rupnik M. , Kreft M. , Nothias F. , Grilc S. , Bobanovic L. K. , Johannes L. , Kiauta T. , Vernier P. , Darchen F. , Zorec R.
Published: July 2006

Members of the Rab3 (A–D) subfamily of small GTPases are believed to play a key role in regulated exocytosis. These proteins share ∼80% identity at amino acid level. The question of whether isoforms of Rab3 are functionally redundant was the subject of this study. We used RT-PCR analysis, in situ hybridization histochemistry, and confocal microscope-based analysis of immunocytochemistry to show that rat melanotrophs contain about equal amounts of Rab3A and Rab3B transcripts as well as proteins. Therefore, these cells are a suitable model to study the subcellular distribution and the role of these paralogous isoforms in regulated exocytosis. Secretory activity of single cells was monitored with patch-clamp capacitance measurements, and the cytosol was dialyzed with a high-calcium-containing patch pipette solution. Preinjection of antisense oligodeoxyribonucleotides specific to Rab3A, but not to Rab3B, induced a specific blockage of calcium-dependent secretory responses, indicating an exclusive requirement for Rab3A in melanotroph cell-regulated secretion. Although the injection of purified Rab3B protein was ineffective, the injection of recombinant Rab3A proteins into rat melanotrophs revealed that regulated secretion was stimulated by a GTP-bound Rab3A with an intact COOH terminus and inhibited by Rab3AT36N, impaired in GTP binding. These results indicate that Rab3A, but not Rab3B, enhances secretory output from rat melanotrophs and that their function is not redundant.
HO-2 provides endogenous protection against oxidative stress and apoptosis caused by TNF-α in cerebral vascular endothelial cells
Authors: Basuroy Shyamali , Bhattacharya Sujoy , Tcheranova Dilyara , Qu Yan , Regan Raymond F. , Leffler Charles W. , Parfenova Helena
Published: July 2006

Tumor necrosis factor-α (TNF-α) causes oxidative stress and apoptosis in a variety of cell types. Heme oxygenase (HO) degrades heme to bilirubin, an antioxidant, and carbon monoxide (CO), a cell cycle modulator, and a vasodilator. Newborn pig cerebral microvascular endothelial cells (CMVEC) highly express constitutive HO-2. We investigated the role of HO-2 in protection against TNF-α-induced apoptosis in cerebral vascular endothelium. In CMVEC from mice and newborn pigs, 15 ng/ml TNF-α alone, or with 10 μg/ml cycloheximide (CHX) caused apoptosis detected by nuclear translocation of p65 NF-κB, caspase-3 activation, DNA fragmentation, cell-cell contact destabilization, and cell detachment. TNF-α did not induce HO-1 expression in CMVEC. CMVEC from HO-2 knockout mice showed greater sensitivity to apoptosis caused by serum deprivation and TNF-α than did wild-type mice. TNF-α increased reactive oxygen species generation, including hydrogen peroxide and superoxide radicals, as detected by dihydrorhodamine-123 and dihydroethidium. The TNF-α response was inhibited by superoxide dismutase and catalase suggesting apoptosis is oxidative stress related. Inhibition of endogenous HO-2 in newborn pig CMVEC increased oxidative stress and exaggerated apoptosis caused by serum deprivation and TNF-α. In HO-1-overexpressing CMVEC (HO-1 selective induction by cobalt portophyrin), TNF-α did not cause apoptosis. A CO-releasing compound, CORM-A1, and bilirubin blocked TNF-α-induced reactive oxygen species accumulation and apoptosis consistent with the antioxidant and antiapoptotic roles of the end products of HO activity. We conclude that HO-2 is critical for protection of cerebrovascular endothelium against apoptotic changes induced by oxidative stress and cytokine-mediated inflammation.
Mechanical strain regulates syndecan-4 expression and shedding in smooth muscle cells through differential activation of MAP kinase signaling pathways
Authors: Julien Matheau A. , Wang Peiyi , Haller Carolyn A. , Wen Jing , Chaikof Elliot L.
Published: July 2006

Syndecan-4 (S4) belongs to a family of transmembrane proteoglycans, acts as a coreceptor for growth factor binding as well as cell-matrix and cell-cell interactions, and is induced in neointimal smooth muscle cells (SMCs) after balloon catheter injury. We investigated S4 expression in SMCs in response to several force profiles and the role of MAP kinase signaling pathways in regulating these responses. S4 mRNA expression increased in response to 5% and 10% cyclic strain (4 h: 200 ± 34% and 182 ± 17%, respectively; P < 0.05) before returning to basal levels by 24 h. Notably, the SMC mechanosensor mechanism was reset after an initial 24-h “preconditioning” period, as evident by an increase in S4 gene expression following a change in cyclic stress from 10% to 20% (28 h: 181 ± 1%; P < 0.05). Mechanical stress induced a late decrease in cell-associated S4 protein levels (24 h: 70 ± 6%; P < 0.05), with an associated increase in S4 shedding (24 h: 537 ± 109%; P < 0.05). To examine the role of MAP kinases, cells were treated with U-0126 (ERK1/2 inhibitor), SB-203580 (p38 inhibitor), or JNKI I (JNK/SAPK inhibitor). Late reduction in cell-associated S4 levels was attributed to ERK1/2 and p38 signaling. In contrast, accelerated S4 shedding required both ERK1/2 (5-fold reduction in accelerated shedding; P < 0.05) and JNK/SAPK (4-fold reduction; P < 0.05) signaling. Given the varied functions of S4, stress-induced effects on SMC S4 expression and shedding may represent an additional component of the proinflammatory, growth-stimulating pathways that are activated in response to changes in the mechanical microenvironment of the vascular wall.
Orphan nuclear receptors: therapeutic opportunities in skeletal muscle
Authors: Smith Aaron G. , Muscat George E. O.
Published: July 2006

Nuclear hormone receptors (NRs) are ligand-dependent transcription factors that bind DNA and translate physiological signals into gene regulation. The therapeutic utility of NRs is underscored by the diversity of drugs created to manage dysfunctional hormone signaling in the context of reproductive biology, inflammation, dermatology, cancer, and metabolic disease. For example, drugs that target nuclear receptors generate over $10 billion in annual sales. Almost two decades ago, gene products were identified that belonged to the NR superfamily on the basis of DNA and protein sequence identity. However, the endogenous and synthetic small molecules that modulate their action were not known, and they were denoted orphan NRs. Many of the remaining orphan NRs are highly enriched in energy-demanding major mass tissues, including skeletal muscle, brown and white adipose, brain, liver, and kidney. This review focuses on recently adopted and orphan NR function in skeletal muscle, a tissue that accounts for ∼35% of the total body mass and energy expenditure, and is a major site of fatty acid and glucose utilization. Moreover, this lean tissue is involved in cholesterol efflux and secretes that control energy expenditure and adiposity. Consequently, muscle has a significant role in insulin sensitivity, the blood lipid profile, and energy balance. Accordingly, skeletal muscle plays a considerable role in the progression of dyslipidemia, diabetes, and obesity. These are risk factors for cardiovascular disease, which is the the foremost cause of global mortality (>16.7 million deaths in 2003). Therefore, it is not surprising that orphan NRs and skeletal muscle are emerging as therapeutic candidates in the battle against dyslipidemia, diabetes, obesity, and cardiovascular disease.
Innate immune response in CF airway epithelia: hyperinflammatory?
Authors: Machen Terry E.
Published: July 2006

The lack of functional cystic fibrosis (CF) transmembrane conductance regulator (CFTR) in the apical membranes of CF airway epithelial cells abolishes cAMP-stimulated anion transport, and bacteria, eventually including Pseudomonas aeruginosa, bind to and accumulate in the mucus. Flagellin released from P. aeruginosa triggers airway epithelial Toll-like receptor 5 and subsequent NF-κB signaling and production and release of proinflammatory cytokines that recruit neutrophils to the infected region. This response has been termed hyperinflammatory because so many neutrophils accumulate; a response that damages CF lung tissue. We first review the contradictory data both for and against the idea that epithelial cells exhibit larger-than-normal proinflammatory signaling in CF compared with non-CF cells and then review proposals that might explain how reduced CFTR function could activate such proinflammatory signaling. It is concluded that apparent exaggerated innate immune response of CF airway epithelial cells may have resulted not from direct effects of CFTR on cellular signaling or inflammatory mediator production but from indirect effects resulting from the absence of CFTRs apical membrane channel function. Thus, loss of Cl−, HCO3−, and glutathione secretion may lead to reduced volume and increased acidification and oxidation of the airway surface liquid. These changes concentrate proinflammatory mediators, reduce mucociliary clearance of bacteria and subsequently activate cellular signaling. Loss of apical CFTR will also hyperpolarize basolateral membrane potentials, potentially leading to increases in cytosolic [Ca2+], intracellular Ca2+, and NF-κB signaling. This hyperinflammatory effect of CF on intracellular Ca2+ and NF-κB signaling would be most prominently expressed during exposure to both P. aeruginosa and also endocrine, paracrine, or nervous agonists that activate Ca2+ signaling in the airway epithelia.
Conserved cysteine residues in the pore region are obligatory for human TRPM2 channel function
Authors: Mei Zhu-Zhong , Mao Hong-Ju , Jiang Lin-Hua
Published: July 2006

TRPM2 proteins belong to the melastatin-related transient receptor potential or TRPM subfamily and form Ca2+-permeable cationic channels activated by intracellular adenosine diphosphoribose (ADPR). The TRPM2 channel subunit, like all its close relatives, is structurally homologous to the well-characterized voltage-gated potassium channel subunits, each containing six transmembrane segments and a putative pore loop between the fifth and sixth segments. Nevertheless, the structural elements determining the TRPM2 channel functions are still not well understood. In this study, we investigated the functional role of two conserved cysteine residues (at positions 996 and 1008) in the putative pore region of the human TRPM2 by site-directed mutagenesis, combined with electrophysiological and biochemical approaches. Expression of wild-type hTRPM2 channels in human embryonic kidney (HEK-293) cells resulted in robust ADPR-evoked currents. Substitution of cysteine with alanine or serine generated mutant channels that failed to be activated by ADPR. Furthermore, experiments done by Western blot analysis, immunocytochemistry, biotin labeling, and coimmunoprecipitation techniques showed no obvious changes in protein expression, trafficking or membrane localization, and the ability to interact with neighboring subunits that is required for channel assembly. Coexpression of wild-type and mutant subunits significantly reduced the ADPR-evoked currents; for the combination of wild-type and C996S mutant subunits, the reduction was ∼95%, indicating that incorporation of one or more nonfunctional C996S subunits leads to the loss of channel function. These results taken together suggest that the cysteine residues in the pore region are obligatory for TRPM2 channel function.
Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse
Authors: Alba Maria , Fintini Danilo , Sagazio Alessia , Lawrence Betty , Castaigne Jean-Paul , Frohman Lawrence A. , Salvatori Roberto
Published: July 2006

Although the majority of children with isolated growth hormone (GH) deficiency have a good growth response to GH-releasing hormone (GHRH), the use of this therapeutic agent is limited by its very short half-life. Indeed, we have shown that, in mice with GHRH gene ablation (GHRH knockout; GHRHKO), even twice-daily injections of a GHRH analog are unable to normalize growth. CJC-1295 is a synthetic GHRH analog that selectively and covalently binds to endogenous albumin after injection, thereby extending its half-life and duration of action. We report the effects of CJC-1295 administration in GHRHKO animals. Three groups of 1-wk-old GHRHKO mice were treated for 5 wk with 2 μg of CJC-1295 at intervals of 24, 48, and 72 h. Placebo-treated GHRHKO mice and mice heterozygous for the GHRHKO allele served as controls. GHRHKO animals receiving daily doses of CJC-1295 exhibited normal body weight and length. Mice treated every 48 and 72 h reached higher body weight and length than placebo-treated animals, without full growth normalization. Femur and tibia length remained normal in animals treated every 24 and 48 h. Relative lean mass and subcutaneous fat mass were normal in all treated groups. CJC-1295 caused an increase in total pituitary RNA and GH mRNA, suggesting that proliferation of somatotroph cells had occurred, as confirmed by immunohistochemistry images. These findings demonstrate that treatment with once-daily administration of CJC-1295 is able to maintain normal body composition and growth in GHRHKO mice. The same dose is less effective when administered every 48 or 72 h.