bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic value of transpapillary biopsy using double lumen introducer for determination of mucosal extent in extrahepatic bile duct cancer
Authors: Yasuda Ichiro , Enya Masamichi , Moriwaki Hisataka , Tomita Eiichi , Kato Tomohiro , Mukai Tsuyoshi , Adachi Seiji , Kasahara Senji , Asano Takahiko
Published: July 2003

Diagnosis of the upstream extent of extrahepatic bile duct cancer has been difficult via the transpapillary approach, due to the difficulty of obtaining a biopsy sample above the stricture. We developed a new biopsy technique that allows a sample to be taken above the stricture, and prospectively evaluated the new technique's utility. Twenty‐four consecutive patients diagnosed as having possible extrahepatic bile duct cancer by endoscopic retrograde cholangiopancreatography and other imaging tests were included in the study. They initially underwent endoscopic placement of a nasobiliary drainage tube. After improvement of jaundice and cholangitis, the cholangiogram obtained via the tube was examined and transpapillary biopsy was performed using a double lumen catheter under fluoroscopic guidance. The biopsy sampling in the stricture was successful in all cases, and pathological diagnosis was confirmed in all cases. The success rate of the method of upstream diagnosis was also sufficient in cases in which stricture was located below the middle extrahepatic bile duct. However, it was relatively low in cases whose stricture was located in the upper extrahepatic bile duct. Biopsy sampling in the hepatic hilum was also difficult. The transpapillary biopsy technique is useful for determination of the upstream extent of extrahepatic bile duct cancer, especially in cases in which stricture is located in the lower extrahepatic bile duct. Compared to the percutaneous transhepatic approach, it is less invasive and can shorten the preoperative period. It was also seen to be relatively safe, easy and convenient.
Computer‐aided grading system for endoscopic severity in patients with ulcerative colitis
Authors: Sasaki Yoshihiro , Hada Ryukichi , Munakata Akihiro
Published: July 2003

The degree of mucosal redness can be quantified as an index of hemoglobin (IHB) that changes with photographic conditions. The first aim of the present study was to stress the exclusion of γ correction as a critical procedure for reliable measurements of IHB. The second aim was to characterize Matts grade by pictorial parameters in the gray scale picture of IHB and to establish a computer‐aided grading system of endoscopic severity in ulcerative colitis. A total of 130 digital endoscopic pictures of 55 patients with ulcerative colitis (30 Matts 1, 70 Matts 2, 20 Matts 3 and 10 Matts 4) were used. The pictures without γ correction were processed for the mean IHB, SD of IHB, kurtosis of IHB and contrast feature. A computer‐aided grading system was constructed on the basis of Bayes decision theory. Significant increase in the mean IHB was seen when comparing Matts 1 to Matts 2. The SD of IHB or contrast feature significantly increased from Matts 2 to Matts 3 or from Matts 3 to Matts 4. Kurtosis of IHB was significantly larger in Matts 3 than in Matts 1 or Matts 4. Sensitivity and specificity when discriminating Matts 1 from Matts 2, Matts 2 from Matts 3 and Matts 3 from Matts 4 by the grading system were found to be 84 and 96%, 94 and 70%, and 100 and 85%, respectively. The computer‐aided grading system may permit quantitative evaluation of effects of treatments in ulcerative colitis with minimal interobserver variation.
Gastric lipoma successfully treated by endoscopic unroofing
Authors: FUKUDA SHINSAKU , YAMAGATA RYO , MIKAMI TATSUYA , SHIMOYAMA TADASHI , SAWAYA MANABU , UNO YOSHIHARU , TANAKA MASANORI , MUNAKATA AKIHIRO
Published: July 2003

A 64‐year‐old Japanese man was diagnosed with a tumor of the stomach. From the findings of an upper gastrointestinal endoscopy, computed tomography scan and endoscopic ultrasonography, the tumor was suggestive of a gastric lipoma. He was successfully treated by an endoscopic unroofing technique. There remained residual tumor just after unroofing, but it disappeared a month later. There remained only a scar and there has been no recurrence.
Plasminogen activator/plasmin system: A major player in wound healing?
Authors: Li Wai‐Yee , Chong Sheree S. N. , Huang Eunice Y. , Tuan Tai‐Lan
Published: July 2003

The role of the plasminogen activator/plasmin system in fibrinolysis has been well established. Indeed, clinicians worldwide have successfully utilized recombinant tissue‐type plasminogen activator as first‐line treatment of acute myocardial infarction for almost 2 decades. Outside the field of cardiology, there has been increasing excitement regarding the possible contribution of this system in many other important biological processes, including cell adhesion, cell migration, cell–cell signaling, tumor invasion and metastasis, ovulation, and wound healing. In this review, we present evidence in the current literature that the plasminogen activator/plasmin system does have a role in wound healing, looking at both normal and abnormal healing. Furthermore, the invaluable insights provided by numerous transgenic animal experiments are summarized. (WOUND REP REG 2003;11:239–247)
An autologous epidermal equivalent tissue‐engineered from follicular outer root sheath keratinocytes is as effective as split‐thickness skin autograft in recalcitrant vascular leg ulcers
Authors: Tausche Anne‐Kathrin , Skaria Mouna , Böhlen Lorenz , Liebold Kristin , Hafner Jürg , Friedlein Helmut , Meurer Michael , Goedkoop René J. , Wollina Uwe , Salomon Denis , Hunziker Thomas
Published: July 2003

The outer root sheath of hair follicles plays an important role in epidermal regeneration in vivo. Keratinocytes isolated by explantation of outer root sheath tissue have extensive proliferative capacity irrespective of donor age, which probably depends on pluripotent epithelial stem cells residing in the outer root sheath. These keratinocytes can be organotypically grown to epidermal equivalents in vitro. We report here that in a multicenter, randomized phase II study, EpiDex™, a tissue‐engineered, fully differentiated autologous epidermal equivalent derived from keratinocytes of the outer root sheath of plucked anagen hair follicles, is as effective as split‐thickness skin autografting in the promotion of healing and complete closure of recalcitrant vascular leg ulcers. (WOUND REP REG 2003;11:248–252)
Edible mushroom (Agaricus bisporus) lectin inhibits human retinal pigment epithelial cell proliferation in vitro
Authors: Kent David , Sheridan Carl M. , Tomkinson Heather A. , White Sarah J. , Hiscott Paul , Yu Lugang , Grierson Ian
Published: July 2003

The retinal pigment epithelium (RPE) plays a major role in the development of the anomalous retinal scarring response termed proliferative vitreoretinopathy. The present study was undertaken to investigate whether agaricus bisporus lectin inhibited human RPE proliferation in vitro. Fluorescein isothiocyanate‐labeled agaricus bisporus lectin was used to study binding of lectin to cultured human RPE. The effect of a 24‐hour exposure of agaricus bisporus lectin on RPE proliferation was measured using (methyl‐3H)‐thymidine incorporation into DNA. Toxicity studies were assessed using morphologic evaluation, trypan blue exclusion, and a cell viability assay. Agaricus bisporus lectin bound to RPE cells and was inhibited by preincubation of lectin with asialomucin. Agaricus bisporus lectin caused a dose‐dependent inhibition of RPE proliferation (one‐way ANOVA, F = 94.470, p < 0.001) that was partially reversible on removal of the lectin. Compared with controls, cells remained viable and no morphological changes or trypan blue staining was noted in RPE exposed to agaricus bisporus lectin. Human RPE binds agaricus bisporus lectin and inhibits proliferation without apparent cytotoxicity. It therefore merits consideration as a potential antiproliferative agent in the prevention and treatment of proliferative vitreoretinopathy and other nonocular anomalous wound healing processes. (WOUND REP REG 2003;11:285–291)
A clinical model of dermal wound angiogenesis
Authors: Lockhart A. Craig , Braun Rod D. , Yu Daohai , Ross Joel R. , Dewhirst Mark W. , Klitzman Bruce , Yuan Fan , Grichnik James M. , Proia Alan D. , Conway Delina A. , Mann Gretchen , Hurwitz Herbert I.
Published: July 2003

Full‐thickness dermal biopsies were performed in healthy volunteers to establish the range of angiogenic responses in wound healing in a normal population. Four‐millimeter punch biopsies were made in the forearms of 15 healthy volunteers. Each wound was evaluated microscopically 4–5 times per week for 2 weeks. A semiquantitative wound scoring system to evaluate the neovasculature at the wound periphery was investigated. A vascular score was calculated for each wound at each observation. Two independent observers analyzed the microscopic wound images using the scoring system. At the end of the 14‐day period, repeat biopsies were performed on some of the volunteers, and the granulation tissue was stained with anti‐CD31. The Kaplan‐Meier method was used to estimate the distribution of the time to reach predetermined target average vascular scores. A mixed‐effects regression model indicated that time, age, and observer were predictors for the average vascular score outcome. The pattern and time course for wound neovascularization was highly reproducible in this group of healthy volunteers, and the assay was feasible and well tolerated. This wound angiogenesis model may be useful for monitoring the effects of antiangiogenic agents on normal wound neovascularization. (WOUND REP REG 2003;11:306–313)
The effect of low-dose potassium supplementation on blood pressure in apparently healthy volunteers
Authors: Naismith Donald J. , Braschi Alessandro
Published: July 2003

Epidemiological and clinical trials suggest an inverse relationship between dietary K intake and blood pressure (BP). Most trials however have been of short duration, the dose of K was high, and the results have been conflicting. The aim of the present study was to evaluate the effect on BP of a low-dose supplementation (24 mmol/d) for an extended period. A double-blind placebo-controlled trial was conducted on fifty-nine volunteers, randomly assigned to receive 24 mmol slow-release KC1/d (n30) or a placebo (n29). Measures of BP, anthropometric characteristics and urine analysis for electrolytes were recorded during a 1-week baseline period. Supplementation was for 6 weeks during which BP and changes in weight were assessed and a second 24h urine collection made. The primary outcome was the change in mean arterial pressure (MAP); systolic BP(SBP) and diastolic BP(DBP) were secondary outcomes. After 6 weeks of supplementation MAP was reduced by 7·01 (95% CI −9·12, −4·89;P<0·001) mmHg, SBP was reduced by 7·60 (95% CI −10·46, −4·73;P<0·001) mmHg and DBP was reduced by 6·46 (95% CI −8·74, −4·19;P<0·001) mmHg. The reduction in MAP was positively associated with baseline urinary Na:K (P<0·034). A low daily dietary supplement of K, equivalent to the content of five portions of fresh fruits and vegetables, induced a substantial reduction in MAP, similar in effect to single-drug therapy for hypertension.
Iron deficiency andin vitroiron chelation reduce the expression of cluster of differentiation molecule (CD)28 but not CD3 receptors on murine thymocytes and spleen cells
Authors: Kuvibidila Solo R. , Porretta Connie
Published: July 2003

Cluster of differentiation molecule (CD)3 and CD28 receptors play crucial roles in T-lymphocyte proliferation. Fe deficiency in man and animals impairs T-lymphocyte proliferation by unknown mechanisms. To test the hypothesis that reduced CD3 and CD28 expression is one of them, thymocytes and splenocytes from control (C;n24), Fe-deficient (ID;n24), pair-fed (PF;n24), and ID mice that were Fe-repleted for 3 (R3;n24) or 14d (R14;n12) were labelled with anti-CD3-fluorescein isothiocyanate and anti-CD28-phycoerythrin antibodies. Positive cells were analysed by flow cytometry. Significant differences were observed among groups in the mean levels of haemoglobin and liver Fe stores (C=PF=R14>R3>ID;P<0·005). While Fe deficiency slightly increased the percentage of CD3+ splenocytes, it reduced that of CD28+ thymocytes in mice with thymus atrophy and splenomegaly (P<0·05). These changes were corrected by Fe repletion. CD28 mean fluorescence intensity (FI) was lower and CD3 FI was higher in lymphocytes from R3 and ID, especially those with splenomegaly, than in those from R14 and PF mice (P<0·05).In vitroFe chelation by deferoxamine (60min) significantly decreased CD28 expression (P<0·05), and slightly increased that of CD3 (P>0·05). Spleen cell proliferative responses to concanavalin A and anti-CD3±anti-CD28 were reduced by Fe deficiency (ID≤R3<C=PF<R14;P<0·05); and they correlated with FI and percentages of CD3+ and CD28+ cells (r≤0·69;P<0·05). Indicators of Fe status negatively correlated with CD3 FI (r−0·23), but positively correlated with CD28 FI (r≤0·44;P<0·05). Data suggest that altered CD28 expression may contribute to reduced T-cell proliferation during Fe deficiency.
Monocyte chemoattractant protein-1 involvement in the α-tocopherol-induced reduction of atherosclerotic lesions in apolipoprotein E knockout mice
Authors: Peluzio Maria C. G. , Miguel Emir , Drumond Thaís C. , César Giovana C. , Santiago Helton C. , Teixeira Mauro M. , Vieira Enio C. , Arantes Rosa M. E. , Alvarez-Leite Jacqueline I.
Published: July 2003

We studied the effects of α-tocopheryl acetate supplementation on the development of fatty streaks and its ability to modulate the expression of monocyte chemoattractant protein (MCP)-1 in aortic lesions of apoliprotein E knockout mice. For this purpose, 16-week-old apolipoprotein E knockout mice received α-tocopherol supplemention ((800 mg)/kg diet) for 6 weeks. After this time, total and lipoprotein cholesterol in the serum, hepatic tocopherol, aortic lesion area and MCP-1 (protein and mRNA) expression were analysed. Our present results showed that the dietary supplementation with α-tocopherol did not reduce serum cholesterol nor change lipoprotein profile, but it reduced the area of the aortic lesion by 55%. The reduction in the lesion size was correlated with the reduced expression of MCP-1 mRNA and protein, as detected by real-time quantitative polymerase chain reaction and immunohistochemistry respectively. In conclusion, the results obtained here are relevant to the study of atherosclerosis, as they correlate the effectiveness of vitamin E supplementation in inhibiting the plaque formation with diminished expression of MCP-1 at the aortic lesion.
Nutritional limitations to increased production on pasture-based systems
Authors: Kolver Eric S.
Published: July 2003

The constraints to high levels of milk production imposed by a high-quality-pasture diet, and development of feeding strategies to overcome these limitations, were examined by modelling the nutritional status of New Zealand Friesian and North American Holstein–Friesian dairy cows grazing high-quality pasture. The Cornell Net Carbohydrate and Protein System (CNCPS) was used to predict sensitivity of milk production to a 10 % change in the composition of pasture nutrients. The rate at which fibre and protein were degraded in the rumen and the value given to effective fibre and lignin content significantly affected the supply of metabolisable energy and protein, and the profile of amino acid supply. The first limiting factor in milk production when only high-quality pasture was fed was metabolisable energy supply, while specific amino acids, particularly methionine and lysine, limited milk production when > 20 g/kg diet consisted of a grain supplement. Compared with cows fed a total mixed ration in confinement, North American Holstein–Friesians grazing all pasture produced less milk (29.6 v. 44.1 kg/d). Of the difference in milk production 61 % could be attributed to a lower DM intake (19 kg/d v. 23.4 kg/d). Predictions using the CNCPS indicated that supply of metabolisable energy was the first-limiting factor for milk production from high-quality pasture (251 g crude protein (N× 6.25)/kg, 432 g neutraldetergent fibre/kg, 77 % in vitro DM digestibility), rather than metabolisable protein or amino acids. In addition, these nutritional limitations imposed by pasture diets will be greater for dairy cow genotypes that have not been selected for high performance within a pasture system.
Prolactin, prolactin receptor and uncoupling proteins during fetal and neonatal development
Authors: Pearce S. , Mostyn A. , Alves-Guerra M. C. , Pecqueur C. , Miroux B. , Webb R. , Stephenson T. , Symonds M. E.
Published: July 2003

Uncoupling proteins (UCP) 1 and 2 are members of the subfamily of inner mitochondrial membrane carriers. UCP1 is specific to brown adipose tissue (BAT), where it is responsible for the rapid production of heat at birth. In fetal sheep UCP1 is first detectable at approximately 900d of gestation; its abundance increases with gestational age and peaks at the time of birth. The mRNA and protein for both the long and short form of the prolactin (PRL) receptor (PRLR) are also highly abundant in BAT. Enhanced PRLR abundance in late gestation is associated with an increase in the abundance of UCP1. This relationship between PRLR and UCP is not only present in BAT. Similar findings are now reported in the pregnant ovine uterus, where PRLR abundance reaches a maximum just before that of UCP2. However, the role of PRLR in BAT remains undetermined. Rat studies have shown that PRL administration throughout pregnancy results in offspring with increased UCP1 at birth. Studies in newborn lambs have shown that administration of PRL (20mg/d) causes an acute response, increasing colonic temperature in the first hour by 1°. This increased colonic temperature is maintained for the first 240h of life, in conjunction with enhanced lipolysis. After 70d of treatment there is no difference in the abundance of UCP1 but an increase in UCP1 activity; this effect may be mediated by an increase in lipolysis. Taken together these findings suggest that PRL could be an important endocrine factor during pregnancy and early postnatal life.
Changes in haemostasis during normal pregnancy: does homocysteine play a role in maintaining homeostasis?
Authors: Holmes Valerie A.
Published: July 2003

Homocysteine, derived from the demethylation of the ammo acid methionine, is either further catabolised by trans-sulfuration to cysteine or remethylated to methionine. Remethylation to methionine requires the cofactors, folate and vitamin B12. Folate is an effective homocysteine-lowering agent and, thus, homocysteine and folate status are inversely related. Hyperhomocysteinaemia is a strong independent risk factor for venous thromboembolism (VTE) and is associated with adverse pregnancy outcomes such as pre-eclampsia, placental abruption, early pregnancy loss and neural-tube defects. Pregnancy is a risk factor for VTE as a result of prothrombotic changes in levels of haemostatic factors. However, despite this hypercoagulable state, the incidence of pregnancy-associated VTE is relatively low. Hyperhomocysteinaemia is associated with abnormalities in markers of coagulation activation, and recent research suggests that folic acid supplementation, as well as lowering homocysteine, lowers markers of coagulation activation and increases levels of coagulation inhibitors. Tissue factor (TF) is the initiator of blood coagulationin vivo, and homocysteine induces TF expressionin vitro. During pregnancy, monocyte TF expression is lower than that in the non-pregnant state, and this lowering of TF may act to counterbalance increases in coagulation activation. Furthermore, despite a high folate requirement, several studies have reported that homocysteine is lower in normal pregnancy than in the non-pregnant state. Although the exact mechanism of homocysteine lowering during pregnancy is unclear, one possible outcome of lower homocysteine may be the protection of women from pregnancy complications and VTE, and thus lower homocysteine may contribute to maintaining homeostasis in haemostasis.
Folate, DNA methylation and colo-rectal cancer
Authors: Pufulete Maria , Emery Peter W. , Sanders Thomas A. B.
Published: July 2003

Prospective cohort and case-control studies suggest an association between low folate intake and increased risk of colo-rectal adenoma and cancer. Some, but not all, animal studies indicate that folate supplementation protects against the development of colo-rectal neoplasms, although supraphysiological folate doses have been shown to enhance tumour growth. Folate is a methyl donor for nucleotide synthesis and biological methylation reactions, including DNA methylation. A low dietary folate intake may increase the risk of colo-rectal neoplasia by inducing genomic DNA hypomethylation, which can affect the expression of proto-oncogenes and tumour suppressor genes associated with the development of cancer. Common polymorphisms in genes involved in the methylation pathway, such as methylenetetrahydrofolate reductase and methionine synthase, have been shown to influence risk of colo-rectal neoplasia, with interactions dependent on folate status and/or alcohol intake, which is known to antagonise methyl group availability. There is some evidence to show that DNA from normal-appearing colo-rectal mucosa in individuals with colo-rectal cancer is hypomethylated. In a case-control study DNA methylation in normal-appearing colo-rectal mucosa has been shown to be lower in individuals with colo-rectal cancer (P=0.08) and colo-rectal adenoma (P=0.009) than in controls free of colo-rectal abnormalities. Human intervention trials to date suggest that supraphysiological doses of folate can reverse DNA hypomethylation in colo-rectal mucosa of individuals with colo-rectal neoplasia. In a double-blind randomised placebo-controlled study folate supplementation at physiological doses has been shown to increase DNA methylation in leucocytes (P=0.05) and colonic mucosa (P=0.09). Further studies are required to confirm these findings in larger populations and to define abnormal ranges of DNA methylation.
Calcium and protein in bone health
Authors: Dawson-Hughes Bess
Published: July 2003

Dietary protein has several opposing effects on Ca balance and its net effect on bone is not well established. It has long been recognized that increasing protein intake increases urinary Ca excretion. More recently, it has been observed that increasing dietary protein raises the circulating level of insulin-like growth factor-1, a growth factor that promotes osteoblast formation and bone growth. Other effects of protein on the Ca economy have been suggested in some studies, but they are less well established. Several studies have examined associations between protein intake and bone loss and fracture rates. In the original Framingham cohort subjects with lower total and animal protein intakes had greater rates of bone loss from the femoral neck and spine than subjects consuming more protein. In another study higher total (and animal) protein intakes were associated with a reduced incidence of hip fractures in post-menopausal women. In contrast, a high animahplant protein intake has been associated with greater bone loss from the femoral neck and a greater risk of hip fracture in older women. Higher total and higher animal protein intakes have also been associated with increased risk of forearm fracture in younger post-menopausal women. In a recent study it was found that increasing dietary protein was associated with a favourable (positive) change in bone mineral density of the femoral neck and total body in subjects taking supplemental calcium citrate malate with vitamin D, but not in those taking placebo. The possibility that Ca intake may influence the impact of dietary protein on the skeleton warrants further investigation.
Should scholarly societies embrace open access (or is it the kiss of death)?
Authors: Velterop Jan
Published: July 2003

In assessing the role that organizations of scientists with publishing activities – such as scholarly societies – can or should play in furthering the science and practice in their chosen fields, they face a dilemma: should they primarily be fund‐raising organizations for other activities in their disciplines, using their publications to bring in the necessary money, or should they be promoters of efficient scholarly communication and use their publications more directly to that end – for instance, by embracing ‘open access‘.
Development and the Environment in Asia
Authors: Coxhead Ian
Published: July 2003

Economic growth and environmental damage are associated, but the relationship is neither linear nor even monotonic. This is clearly seen in the diverse experiences of tropical Asian economies over recent decades. The nature of the growth–environment link depends on the changing composition of production and on growth‐related changes in techniques and environmental policies; the enforcement of property rights over natural resources and over air and water quality is another important element. Moreover, environmental and economic policies interact: in effect, every economic policy that affects resource allocation is a de facto environmental measure. One important implication is that the environmental consequences of major policy shifts, such as the ‘globalisation’ of many tropical Asian economies since about 1980, have been profound. The analytical literature on growth and the environment in Asia tends to agree that environmental damage is costly to regional economies, and has begun to identify and quantify some of the many causal linkages now recognised between economic development and the valuation and use of environmental and natural resource assets.
Can Market Power Influence Employment, Wage Inequality and Growth?
Authors: Bucci Alberto , Fiorillo Fabio , Staffolani Stefano
Published: July 2003

We introduce an efficiency wage mechanism into an innovation‐driven growth model. Due to asymmetric information problems the labour market is segmented and homogeneous workers may be employed either in the non‐competitive intermediate sector or in the competitive research sector. We analyse the impact that the monopoly position enjoyed by intermediate firms in the product market may have on employment, wage inequality and growth, and the sectoral distribution of workers. We find that the lower the product market competition in the capital goods sector, the higher the research employment, the lower the intermediate sector employment and the higher the growth rate. The relationships between growth and inequality, on the one hand, and between growth and employment, on the other, are both negative.
Aggregation in Production Functions: What Applied Economists should Know
Authors: Felipe Jesus , Fisher Franklin M.
Published: July 2003

There is no subject so old that something new cannot be said about it.

(Dostoevsky)

Glendower: I can call spirits from the vasty deep

Hotspur: Why, so can I, or so can any man;   But will they come when you do call for them?

(Shakespeare, Henry IV, Part I, Act III, Scene I)

This paper surveys the theoretical literature on aggregation of production functions. The objective is to make neoclassical economists aware of the insurmountable aggregation problems and their implications. We refer to both the Cambridge capital controversies and the aggregation conditions. The most salient results are summarized, and the problems that economists should be aware of from incorrect aggregation are discussed. The most important conclusion is that the conditions under which a well‐behaved aggregate production function can be derived from micro production functions are so stringent that it is difficult to believe that actual economies satisfy them. Therefore, aggregate production functions do not have a sound theoretical foundation. For practical purposes this means that while generating GDP, for example, as the sum of the components of aggregate demand (or through the production or income sides of the economy) is correct, thinking of GDP as GDP=F(K, L), where K and L are aggregates of capital and labor, respectively, and F(•) is a well‐defined neoclassical function, is most likely incorrect. Likewise, thinking of aggregate investment as a well‐defined addition to ‘capital’ in production is also a mistake. The paper evaluates the standard reasons given by economists for continuing to use aggregate production functions in theoretical and applied work, and concludes that none of them provides a valid argument.
Spatial Crime Patterns and the Introduction of the UK Minimum Wage*
Authors: Hansen Kirstine , Machin Stephen
Published: July 2003

This paper provides an empirical evaluation of whether one can uncover a link between crime and the labour market using a research methodology that is different to that utilized in existing work. We exploit a large regulatory change that was made to the UK labour market when a national minimum wage was introduced in April 1999. This minimum wage introduction provided pay increases for quite a large number of low paid workers. From a theoretical perspective we argue that this wage boost could have altered individual incentives to participate in crime. We then go on to develop empirical tests of this hypothesis comparing spatial crime patterns, measured at police force area level, in the years before and after the introduction of the minimum wage floor. Our empirical study of area‐level crime rates before and after the minimum wage introduction uncovers a statistically significant link between changes in crime and the extent of area low pay before the minimum wage was introduced. Overall our results are in line with the notion that altering wage incentives can affect crime and therefore that there exists a link between crime and the low wage labour market.
Looking for a Needle in a Haystack? A Re‐examination of the Time Series Relationship between Teenage Employment and Minimum Wages in the United States*
Authors: Bazen Stephen , Marimoutou Velayoudom
Published: July 2003

The work of Card and Krueger has cast doubt on the nature of the relationship between the minimum wage and teenage employment in the United States. The earlier ‘consensus’ finding of a small but statistically significant negative effect was based on time series data whereas Card and Krueger's findings are based mainly on cross‐section data. In this article, we re‐examine the time series relationship between minimum wage and teenage employment. We find that previous models break down due to their inability to capture changes in the trend, cyclical and seasonal components of teenage employment. We propose an alternative approach in which these components are treated as stochastic components and which contains the traditional, deterministic approach as a special case. The model when estimated up to 1979 accurately predicts what happens to teenage employment subsequently, when the minimum wage was frozen after 1981 and then increased quite substantially in the early 1990s. Moreover, we find that there is a significant, negative effect of the minimum wage on teenage employment and its size has hardly changed during the 1980s and early 1990s.
Administration of C1 Inhibitor Reduces Neutrophil Activation in Patients with Sepsis
Authors: Zeerleder Sacha , Caliezi Christoph , van Mierlo Gerard , Eerenberg-Belmer Anke , Sulzer Irmela , Hack C. Erik , Wuillemin Walter A.
Published: July 2003

Forty patients with severe sepsis or septic shock recently received C1 inhibitor. In the present study we studied the effect of C1 inhibitor therapy on circulating elastase-α1-antitrypsin complex (EA) and lactoferrin (LF) levels in these patients to gain further insight about agonists involved in the activation of neutrophils in human sepsis. Elevated levels of EA and LF were found in 65 and 85% of the septic patients, respectively. Patients with elevated EA levels had higher organ dysfunction scores, higher levels of cytokines, and higher levels of complement activation products than patients with normal EA levels. C1 inhibitor therapy reduced EA as well as complement activation and IL-8 release in the patients with elevated EA on admission. We conclude that neutrophil activation in human sepsis correlates with the severity of organ dysfunction and involves complement and interleukin-8 as agonists. The effect of C1 inhibitor therapy on neutrophils may provide an explanation for the beneficial, although mild, effects of this treatment on organ dysfunction in sepsis.
Detection of High Titers of Antibody against
Helicobacter
Cysteine-Rich Proteins A, B, C, and E in
Helicobacter pylori
-Infected Individuals
Authors: Mittl Peer R. E. , Lüthy Lucas , Reinhardt Christoph , Joller Hellen
Published: July 2003

The family of
Helicobacter
cysteine-rich proteins (Hcp) constitutes one of the largest protein families that are specific for proteobacteria from the delta/epsilon subgroup. Most of the proteins belonging to this family have so far only been recognized on the genome level. To investigate the expression of Hcp proteins in vivo we analyzed titers of antibody against HcpA (HP0211), HcpB (HP0336), HcpC (HP1098), and HcpE (HP0235) in sera from 30
Helicobacter pylori
-positive individuals and in a control group of six
H. pylori
-negative individuals. Significantly higher titers of antibody were observed for
H
.
pylori
-positive individuals (
P
< 0.00005). The highest and lowest titers were observed for HcpC (Δ mean = 1.06) and HcpB (Δ mean = 0.333), respectively. There is a clear correlation among anti-HcpA, -HcpC, and -HcpE immunoglobulin G titers in
H
.
pylori
-positive individuals (correlation > 0.7), but there is only a weak correlation for HcpB (correlation < 0.4). These results confirm that Hcp proteins are expressed by
H. pylori
under natural environmental conditions and that these proteins are recognized by the immune system of the host. The observed correlations are in agreement with the expected distribution of Hcp proteins among
H. pylori
strains. HcpA, HcpC, and HcpE are present in the genomes of strains 26695 and J99, whereas HcpB is absent from most strains. Since Hcp proteins are specific for
H. pylori
, immunological assays including Hcp proteins might be of value to detect
H. pylori
infection and perhaps to distinguish among different groups of
H
.
pylori
-positive patients.
Adrenomedullin Expression by Gastric Epithelial Cells in Response to Infection
Authors: Allaker Robert P. , Kapas Supriya
Published: July 2003

Many surface epithelial cells express adrenomedullin, a multifunctional peptide found in a wide number of body and cell systems. Recently, we and others have proposed that adrenomedullin has an important novel role in host defense. This peptide has many properties in common with other cationic antimicrobial peptides, including the human β-defensins. Upon exposure of human gastric epithelial cells to viable cells of invasive or noninvasive strains ofHelicobacter pylori,Escherichia coli,Salmonella enterica, orStreptococcus bovis, a significant increase in adrenomedullin secretion from these cells was demonstrated. Adrenomedullin gene expression was also increased in response to these microorganisms. Similar observations were noted when these cells were incubated with proinflammatory cytokines such as interleukin 1α (IL-1α), IL-6, tumor necrosis factor alpha and lipopolysaccharide. In cultured cells and an animal infection model, increased adrenomedullin peptide and gene expression was demonstrated when exposed toE. coliorMycobacterium paratuberculosis, respectively. The data suggest there is a strong association between epithelial infection, inflammation, and adrenomedullin expression, which may have clinical relevance. The regulation of adrenomedullin expression may have therapeutic applications, such as improving or enhancing mucosal immunity.
Infection withMycobacterium bovisBCG Diverts Traffic of Myelin Oligodendroglial Glycoprotein Autoantigen-Specific T Cells Away from the Central Nervous System and Ameliorates Experimental Autoimmune Encephalomyelitis
Authors: Sewell Diane L. , Reinke Emily K. , Co Dominic O. , Hogan Laura H. , Fritz Robert B. , Sandor Matyas , Fabry Zsuzsa
Published: July 2003

Infectious agents have been proposed to influence susceptibility to autoimmune diseases such as multiple sclerosis. We induced a Th1-mediated central nervous system (CNS) autoimmune disease, experimental autoimmune encephalomyelitis (EAE) in mice with an ongoing infection withMycobacterium bovisstrain bacillus Calmette-Guérin (BCG) to study this possibility. C57BL/6 mice infected with live BCG for 6 weeks were immunized with myelin oligodendroglial glycoprotein peptide (MOG35-55) to induce EAE. The clinical severity of EAE was reduced in BCG-infected mice in a BCG dose-dependent manner. Inflammatory-cell infiltration and demyelination of the spinal cord were significantly lessened in BCG-infected animals compared with uninfected EAE controls. ELISPOT and gamma interferon intracellular cytokine analysis of the frequency of antigen-specific CD4+T cells in the CNS and in BCG-induced granulomas and adoptive transfer of MOG35-55-specific green fluorescent protein-expressing cells into BCG-infected animals indicated that nervous tissue-specific (MOG35-55) CD4+T cells accumulate in the BCG-induced granuloma sites. These data suggest a novel mechanism for infection-mediated modulation of autoimmunity. We demonstrate that redirected trafficking of activated CNS antigen-specific CD4+T cells to local inflammatory sites induced by BCG infection modulates the initiation and progression of a Th1-mediated CNS autoimmune disease.
Detection of Immunoglobulin M Antibodies to Hepatitis E Virus by Class Capture Enzyme Immunoassay
Authors: Yu C. , Engle R. E. , Bryan J. P. , Emerson S. U. , Purcell R. H.
Published: July 2003

The measurement of antibodies to hepatitis E virus (anti-HEV) has been essential for understanding the epidemiology of hepatitis E. Studies to determine the prevalence of HEV infections require a reliable serologic assay that is sensitive and specific. It is also important to distinguish the acute from the convalescent phase of an infection; this usually requires the detection of the immunoglobulin M (IgM) class of antibody. Few enzyme immunoassays (EIAs) that measure IgM anti-HEV have been described, and most have utilized the sandwich method. The present study describes an EIA that detects IgM anti-HEV by antibody class capture methodology. The assay was validated by using serum and/or plasma panels from experimentally infected nonhuman primates. It was used to demonstrate an anamnestic response and the reappearance of IgM anti-HEV in a chimpanzee experimentally challenged with HEV at two different times 45 months apart. The class capture method was more sensitive than the sandwich EIA when used to test clinical samples from two hepatitis E epidemics in Pakistan; it also had the advantage of distinguishing IgM anti-HEV in the presence of high titers of IgG anti-HEV.
Gamma Interferon Responses Induced by a Panel of Recombinant and Purified Mycobacterial Antigens in Healthy, Non-Mycobacterium bovisBCG-Vaccinated Malawian Young Adults
Authors: Black Gillian F. , Weir Rosemary E. , Chaguluka Steven D. , Warndorff David , Crampin Amelia C. , Mwaungulu Lorren , Sichali Lifted , Floyd Sian , Bliss Lyn , Jarman Elizabeth , Donovan Linda , Andersen Peter , Britton Warwick , Hewinson Glyn , Huygen Kris , Paulsen Jens , Singh Mahavir , Prestidge Ross , Fine Paul E. M. , Dockrell Hazel M.
Published: July 2003

We have previously shown that young adults living in a rural area of northern Malawi showed greater gamma interferon (IFN-γ) responses to purified protein derivatives (PPD) prepared from environmental mycobacteria than to PPD fromMycobacterium tuberculosis. In order to define the mycobacterial species to which individuals living in a rural African population have been exposed and sensitized, we tested T-cell recognition of recombinant and purified antigens fromM. tuberculosis(38 kDa, MPT64, and ESAT-6),M. bovis(MPB70),M. bovisBCG (Ag85), andM. leprae(65 kDa, 35 kDa, and 18 kDa) in >600 non-M. bovisBCG-vaccinated young adults in the Karonga District of northern Malawi. IFN-γ was measured by enzyme-linked immunosorbent assay (ELISA) in day 6 supernatants of diluted whole-blood cultures. The recombinantM. leprae35-kDa and 18-kDa and purified nativeM. bovisBCG Ag85 antigens induced the highest percentages of responders, though both leprosy and bovine tuberculosis are now rare in this population. TheM. tuberculosisantigens ESAT-6 and MPT64 and theM. bovisantigen MPB70 induced the lowest percentages of responders. One of the subjects subsequently developed extrapulmonary tuberculosis; this individual had a 15-mm-diameter reaction to the Mantoux test and responded toM. tuberculosisPPD, Ag85, MPT64, and ESAT-6 but not to any of the leprosy antigens. We conclude that in this rural African population, exposure toM. tuberculosisorM. bovisis much less frequent than exposure to environmental mycobacteria such asM. avium, which have antigens homologous to theM. leprae35-kDa and 18-kDa antigens.M. tuberculosisESAT-6 showed the strongest association with the size of the Mantoux skin test induration, suggesting that among the threeM. tuberculosisantigens tested it provided the best indication of exposure to, or infection with,M. tuberculosis.
Efficiency of a Pneumococcal Opsonophagocytic Killing Assay Improved by Multiplexing and by Coloring Colonies
Authors: Kim Kyung Hyo , Yu Jigui , Nahm Moon H.
Published: July 2003

For evaluating pneumococcal vaccines, the opsonophagocytic killing assay (OPKA) is useful as a supplement to the pneumococcal antibody enzyme-linked immunosorbent assay (ELISA). However, evaluations of pneumococcal vaccines require the determination of antibody responses to 7 to 11 serotypes, and the OPKA is tedious to perform and requires more serum than the ELISA. Consequently, the OPKA is infrequently used for evaluating pneumococcal vaccines. To overcome these limitations, we have developed a simple multiplexed (double-serotype) OPKA by using antibiotic-resistant pneumococci for nine serotypes. Serotype 6B, 9V, 19A, and 23F strains were made streptomycin resistant, and serotype 4, 6A, 14, 18C, and 19F strains were made optochin resistant. The multiplexed OPKA was the same as the single-serotype OPKA except for two changes. First, the target bacteria were a mixture of one streptomycin-resistant strain and one optochin-resistant strain. Second, the surviving bacteria of each serotype were enumerated by plating on Todd-Hewitt agar plates with yeast extract and an agar overlay containing the appropriate antibiotics and 2,3,5-triphenyl tetrazolium chloride. The performance of the multiplexed OPKA was evaluated by analyzing 28 serum samples from adults immunized with a 23-valent polysaccharide vaccine by using the single-serotype OPKA and the multiplexed OPKA. The multiplexed OPKA was specific for the desired serotypes. The multiplexed and conventional OPKAs had comparable assay sensitivities and produced results that were highly correlated (

r
2

values ranging from 0.92 to 0.98) for all nine serotypes. A simple modification of the conventional OPKA produces a multiplexed assay that greatly reduces effort, reagents, and the necessary amount of serum.
Comparison of Capture Immunoglobulin M (IgM) and IgG Enzyme-Linked Immunosorbent Assay (ELISA) and Nonstructural Protein NS1 Serotype-Specific IgG ELISA for Differentiation of Primary and Secondary Dengue Virus Infections
Authors: Shu Pei-Yun , Chen Li-Kuang , Chang Shu-Fen , Yueh Yi-Yun , Chow Ling , Chien Li-Jung , Chin Chuan , Lin Ting-Hsiang , Huang Jyh-Hsiung
Published: July 2003

We have found that NS1 serotype-specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) can be used to differentiate primary and secondary dengue virus infections. This is due to the fact that the NS1-specific IgG antibody cannot be detected before day 9 of illness for primary infection, so the NS1-specific IgG antibodies measured in acute-phase sera must come from previous infection. Comparison of NS1 serotype-specific IgG ELISA with envelope- and membrane-specific capture IgM and IgG ELISA in the differentiation of primary and secondary dengue virus infections showed good correlation (95.90% agreement). Most important, we have found that the serotype of the dengue virus from the majority of patients with primary infection could be correctly identified when convalescent-phase or postinfection sera were analyzed by NS1 serotype-specific IgG ELISA. These findings suggested that NS1 serotype-specific IgG ELISA could be reliably applied for serodiagnosis and seroepidemiological study of dengue virus infection.
Levels of Macrophage Inflammatory Protein 1α (MIP-1α) and MIP-1β in Intervillous Blood Plasma Samples from Women with Placental Malaria and Human Immunodeficiency Virus Infection
Authors: Chaisavaneeyakorn Sujittra , Moore Julie M. , Mirel Lisa , Othoro Caroline , Otieno Juliana , Chaiyaroj Sansanee C. , Shi Ya Ping , Nahlen Bernard L. , Lal Altaf A. , Udhayakumar Venkatachalam
Published: July 2003

Macrophage inflammatory protein-1α (MIP-1α) and MIP-1β play an important role in modulating immune responses. To understand their importance in immunity to placental malaria (PM) and in human immunodeficiency virus (HIV)-PM coinfection, we investigated levels of these chemokines in the placental intervillous blood plasma (IVB plasma) and cord blood plasma of HIV-negative PM-negative, HIV-negative PM-positive, HIV-positive PM-negative, and HIV-positive PM-positive women. Compared to HIV-negative PM-negative women, the MIP-1β concentration in IVB plasma was significantly elevated in HIV-negative PM-positive women and HIV-positive PM-positive women, but it was unaltered in HIV-positive PM-negative women. Also, PM-infected women, irrespective of their HIV status, had significantly higher levels of MIP-1β than HIV-positive PM-negative women. The MIP-1α level was not altered in association with either infection. The IVB plasma levels of MIP-1α and MIP-1β positively correlated with the cord blood plasma levels of these chemokines. As with IVB plasma, only cord plasma from PM-infected mothers had significantly elevated levels of MIP-1β compared to PM-negative mothers, irrespective of their HIV infection status. MIP-1β and MIP-1α levels in PM-positive women were positively associated with parasite density and malaria pigment levels. Regardless of HIV serostatus, the IVB MIP-1β level was significantly lower in women with PM-associated anemia. In summary, an elevated level of MIP-1β was associated with PM. HIV infection did not significantly alter these two chemokine levels in IVB plasma.