bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis B core antigen is a potent inductor of interleukin‐18 in peripheral blood mononuclear cells of healthy controls and patients with hepatitis B infection
Authors: Manigold Tobias , Böcker Ulrich , Chen Jingsan , Gundt Jutta , Traber Petra , Singer Manfred V. , Rossol Siegbert
Published: July 2003

Clearance of hepatitis B virus infection (HBV) infection implies a polyclonal vigorous T‐helper 1 (Th1) and cytotoxic T‐lymphocyte (CTL) response. Interleukin‐18 (IL‐18), a monokine that shares functional abilities with IL‐12, is a potent inductor of interferon‐γ (IFN‐γ) by Th1 and natural killer (NK) cells. However, the role and regulation in HBV infection of IFN‐γ have not been defined. This study therefore sought to determine hepatitis B core antigen (HBcAg)‐mediated regulation of IL‐18 production in peripheral blood mononuclear cells (PBMCs) from healthy controls (HC) and patients with chronic hepatitis B (CHB) or acute hepatitis B (AHB); 31 HC, 27 patients with CHB and 8 patients with AHB infection were included in the study. HBcAg‐mediated induction of IL‐18 was determined by quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) and specific enzyme‐linked immunosorbent assay (ELISA). HBcAg induced IL‐18 gene transcription and dose‐dependent secretion of mature IL‐18 protein in HC, CHB, and AHB. HBcAg‐dependent IL‐18 levels were abrogated by inhibition of Caspase‐1, but not by blockade of CD40‐CD154 interaction. Serum levels of IFN‐γ correlated inversely with viremia in patients with CHB (ρ = − 0.54, P < 0.05), but not with serum levels of IL‐12 or IL‐18. Interestingly, in PBMCs of HBeAg‐negative patients, HBcAg induced significantly higher amounts of IL‐18 than in those of HBeAg‐positive patients. A variant, lacking the histone‐like arginine‐rich domain, did not induce IL‐18 in either HC or CHB in vitro. Taken together, these results indicate that HBcAg induces IL‐18 secretion by induction of Caspase‐1. Differential regulation in HBeAg‐negative and positive patients suggests an important role of IL‐18 in CHB infection. J. Med. Virol. 71:31–40, 2003. © 2003 Wiley‐Liss, Inc.
Hepatitis C virus genetic variability in 52 human immunodeficiency virus‐coinfected patients
Authors: Neau Didier , Jouvencel Anne‐Christine , Legrand Elisabeth , Trimoulet Pascale , Galperine Tatiana , Chitty Isabelle , Ventura Michel , Le Bail Brigitte , Morlat Philippe , Lacut Jean‐Yves , Ragnaud Jean‐Marie , Dupon Michel , Fleury Hervé , Lafon Marie‐Edith
Published: July 2003

The aim of this study was to examine whether hepatitis C virus (HCV) pretreatment quasispecies complexity was linked to virological response or other clinical and biological parameters, in human immunodeficiency virus (HIV)‐coinfected patients undergoing anti‐HCV treatment. In addition, HCV quasispecies composition is described longitudinally in these patients before, during, and after treatment. The 52 HIV‐coinfected patients were included in a randomized therapeutic trial. At inclusion, they had CD4+ counts of >250/μl, HIV plasma load of <10,000 copies/ml, and chronic HCV infection with genotype 1 (n = 27), 2 (n = 2) or 3 (n = 23). These values were compared at baseline with 32 HCV‐only‐infected, interferon‐naive patients who were infected with genotype 1, 2, or 3 (n = 16, 1, or 15, respectively). HCV complexity was studied by single‐strand conformation polymorphism (SSCP) in E2 hypervariable region 1 (HVR1), and diversity was evaluated at inclusion in 20 coinfected patients by sequencing four major SSCP bands. The baseline number of SSCP bands was identical in HIV‐infected and control patients. In HIV‐infected patients, HCV complexity was not predictive of sustained virological response to anti‐HCV treatment and was unrelated to epidemiological factors, immunological parameters linked to HIV infection (CD4+ counts, T CD4+ proliferative responses to HIV‐1 p24), protease inhibitor treatment, HCV plasma load, or genotype. HCV diversity was lower in genotype 2‐ and 3‐infected patients. Six months after completion of the anti‐HCV treatment, in comparison with baseline, SSCP profiles were modified in 13 of the 21 nonresponding coinfected patients with analyzable samples. In conclusion, in HIV‐infected patients, HCV variability had no significant influence on virological response to anti‐HCV treatment. J. Med. Virol. 71:41–48, 2003. © 2003 Wiley‐Liss, Inc.
Relevance of B19 markers in serum samples for a diagnosis of parvovirus B19‐correlated diseases
Authors: Gallinella G. , Zuffi E. , Gentilomi G. , Manaresi E. , Venturoli S. , Bonvicini F. , Cricca M. , Zerbini M. , Musiani M.
Published: July 2003

In order to evaluate the optimal and essential diagnostic test(s) for a correct diagnosis of B19 diseases, 344 consecutive serum samples were tested from 344 patients with clinical suspicion of B19 infection during an epidemic period (early Spring–Autumn 2000). Sera were tested for B19 DNA by a standardized competitive polymerase chain reaction‐enzyme‐linked immunosorbent assay (PCR‐ELISA) and dot‐blot hybridization and for specific IgM and IgG by ELISA. Of 344 patients examined, 125 were positive for markers of B19‐associated disease: 49 had both B19 DNA and IgM, 50 had B19 DNA without IgM, and 26 had IgM without B19 DNA. After examination of the different patterns of B19 markers as diagnostic tools for B19 infection, IgM determination detected only 60% of B19‐documented infections. IgM tests were nevertheless fundamental, as they were the unique diagnostic marker in 20.8% of documented infections (26 of 125 patients), in the diagnosis of recent, but still symptomatic infections when B19 DNA was no longer detectable. The determination of B19 DNA with PCR permitted detection of 79.2% of infections and therefore represented an essential test. PCR was fundamental for the diagnosis of B19 disease, as the unique diagnostic marker in 32% of documented infections (50 of 125 patients), both in acute infections at the onset of symptoms before the appearance of immunological response, and during the course of persistent B19 infections in which IgM had cleared. The contemporaneous determination of B19 DNA by PCR and specific IgM appears to be the most appropriate diagnostic protocol for the correct laboratory diagnosis of B19 infection. J. Med. Virol. 71:135–139, 2003. © 2003 Wiley‐Liss, Inc.
Relationship of TT virus and Helicobacter pylori infections in gastric tissues of patients with gastritis
Authors: Maggi Fabrizio , Marchi Santino , Fornai Claudia , Tempestini Elena , Andreoli Elisabetta , Lanini Letizia , Vatteroni Maria Linda , Bellini Massimo , De Bortoli Nicola , Costa Francesco , Pistello Mauro , Specter Steven , Bendinelli Mauro
Published: July 2003

Blood and gastric tissue biopsies of 34 patients with gastritis were tested for the presence of TT virus (TTV), a ubiquitous virus found in the blood of most humans. Thirty‐one of these patients were TTV positive, and 27 patients had virus in both tissues. In addition, 13 of the patients who had TTV in gastric tissue were Helicobacter pylori positive. There was an association of higher TTV titers in gastric tissues of patients who were H. pylori positive than in those in whom the bacterium could not be detected. Furthermore, this association was stronger in H. pylori‐positive patients with the presence of the cagA protein. Of 10 specimens in which genogroup determination was carried out in the gastric corpus, 5/5 that were H. pylori positive showed the presence of TTV genogroup 3, while for those that were H. pylori negative, 5/5 showed the presence of genogroup 1t. By contrast, genogroup 1 was found in the corpus of only one H. pylori‐positive patient, and genogroup 3 in only one H. pylori‐negative patient. The histological severity of gastritis did correlate significantly with loads in the gastric tissues. There was no significant difference in TTV titer in blood of patients regardless of H. pylori infection status. These findings pique interest in clarifying the role of TTV, alone or in association with H. pylori infection, in the pathogenesis of gastritis. J. Med. Virol. 71:160–165, 2003. © 2003 Wiley‐Liss, Inc.
Importance of amino acid 216 in nonstructural protein 2B for replication of hepatitis A virus in cell culture and in vivo
Authors: Graff Judith , Emerson Suzanne U.
Published: July 2003

Clinical isolates of hepatitis A virus (HAV) replicate inefficiently in cell culture unless mutations are acquired throughout the genome. An Ala‐to‐Val substitution in the nonstructural protein 2B (2B‐216) was known to have a major impact on replication in cell culture. Analysis of chimeric viruses confirmed that the 2B‐A[216]V change was critical for efficient replication and that Leu or Ile could substitute for Val. Viruses containing Val, Ile, or Leu at 2B‐216 all replicated with similar kinetics in cell culture, whereas the virus containing Ala at this position grew 10‐ to 20‐fold less efficiently. In contrast, in vivo, virus with either Ala or Val at 2B‐216 replicated equally efficiently when tested in a chimpanzee and in tamarins, and each amino acid was stably maintained. Attempts to complement wild‐type 2B in trans with adapted 2B provided by co‐infection with a second viable HAV mutant failed to enhance replication of the virus containing the wild‐type 2B sequence. J. Med. Virol. 71:7–17, 2003. © 2003 Wiley‐Liss, Inc.
Duration, Systematic Risk, and Employee Valuation of Default-Free Pension Claims
Authors: Nader Jihad S.
Published: July 2003

Lifetime-contract theory assigns a riskless discount rate for sponsor valuation of pension obligations, but does not address the appropriate discount rate for employee valuation of pension promises. This puts in question the use of a riskless discount rate assumption in many studies which analyze pension claim valuation by employees. This article presents a method for assessing the employees’ discount rate for pension claims. The method involves formulating the beta-duration relationship for these claims and combining this relationship with the capital asset pricing model. Numerical illustrations indicate that even for default-free pension promises, the employees’ discount rate includes a systematic risk premium which may be non-negligible for young employees, but diminishes rapidly as employees grow older. i.e. Journal of Risk and Insurance, Vol. LVII, No. 4 (December 1990), pp. 623-633. (Reprinted with permission of The Journal of Rtik and Insurance.)
The Effects of Transaction Costs on Household’s Financial Asset Demands
Authors: Hess Alan C.
Published: July 2003

Changes in risk-adjusted, expected, relative rates of return on financial assets signal rebalancing trades to financial asset owners. Transaction costs reduce the number and frequency of these trades below what they would be if trading costs were smaller or nonexistent. By not trading, households incur implicit costs of holding poorly diversified portfolios. These costs range from $4 billion per year, 0.28% of wealth, to $50 billion per year, 1.6 % of wealth. The costs of not trading depend on the variability of relative rates of return, and the interest elasticities of asset demands. Journal ofMoney, Credit, and Banking, (August 1991), Part 1, pp. 383- 409. (Reprinted with permission of the Journal ofMoney, Credit, and Banking.)
Financial Investment Opportunities and the Macroeconomy
Authors: Chen Nai-Fu
Published: July 2003

This paper studies the relation between changes in financial investment oppor- tunities and changes in the macroeconomy. States variables such as the lagged production growth rate, the default premium, the term premium, the short-term interest rate and the market dividend-price ratio are shown to be indicators of recent and future economic growth. Further, the market excess return is negatively correl- ated with recent economic growth and positively correlated with expected future economic growth. These results offer straightforward interpretations of recent evidence on the forecasts of the market excess return by state variable via their forecasts on the macroeconomy. 7JzeJournal ofFinance, Vol. XLVI, No. 2 (June 1991), pp. 529-54. (Reprinted with permission of 7?zeJournaZ ofFinance.)
Regional Bias in Federal Tax Subsidy Rates for Giving?
Authors: Clotfelter C.T. , Feenberg D.
Published: July 2003

This study examines regional variation in average subsidy rates for charitable donations. The subsidy rate for an individual depends on the taxpayer’s itemization status and marginal tax rate, and this subsidy rate rises with income. One would expect that average subsidy rates would be higher in wealthier regions. What is not clear is whether subsidy rates vary systematically independent of income. In order to examine these questions, the authors decompose subsidy rates independent of income, in what appears to be an unintended regional bias in the federal policy toward charitable giving. Public Finance, Vol. 45, No. 2 (1990), pp. 228-240. (Reprinted with permission of Public Finance.)
Determinants of Relative Investor Demand for Common Stocks
Authors: Cready William M.
Published: July 2003

This paper examines the demand for a firm’s common stock by wealthy relative to less wealthy individual investors and by individual relative to institutional investors as a function of risk, information environment (proxied by firm size and S&P 500 membership), and form of return payout (i.e., dividends versus capital gains.) The findings indicate that among individual investors demand for the stocks of riskier, larger, and low-dividend-yield firms increases with wealth. The findings also suggest that relative to individual investors, institutional investors prefer the stocks of larger firms, S&P 500 firms, and firms paying low dividend yields. Overall, these results suggest that investors find a number of firm-specific factors important in their investment choices and that the importance of such factors varies systematically with investor size. Journal of Accounting, Auditing, & Finance, Summer 1994, 9(3): 487-507. (Reprinted with permission of Journal of Accounting, Auditing, Q Finance.)
Convertible Debt and Investment Incentives
Authors: Harikumar T. , Kadapakkam P. , Singer Ronald F.
Published: July 2003

In this paper we examine the effect of convertible debt on the investment incentives facing stockholders. The effect depends critically on the value of existing assets relative to the firm’s investment requirements. With a restrictive dividend covenant, convertible debt mitigates the overinvestment incentive associated with risky debt but exacerbates the underinvestment incentive at higher values of existing assets. A less-restrictive dividend covenant exacerbates overinvestment under straight debt financing but reduces the underin- vestment incentive induced by the conversion feature. In this context, a convertible debt contract with a less-restrictive dividend covenant maximized firm value. The Journal of Financial Research, Spring 1994, XVII(l): 15-29. (Reprinted with permission of The Journal of Financial Research.)
Common Stochastic Trends in Pacific Rim Stock Markets
Authors: Chung Pin J. , Liu Donald J.
Published: July 2003

A study examines the common stochastic trends among national stock prices of the US and 5 East Asian countries, including Japan, Hong Kong, Taiwan, Singapore, and South Korea. Through Johansen’s (1988, 1991) maximum likelihood estimation procedure, 2 cointegration relationships are identified and the 6 stock price variables are found to share 4 common unit roots. The result suggests that the US and Taiwan markets may not belong to a common stock region containing the remaining 4 countries. The result also shows that most variables have the same adjustment speed in moving from short-run disequilibria toward the common trend. Finally, impulse response analyses suggest that short-run adjust- ments to temporary shocks occur rather quickly for some countries, and that for others, the pattern and magnitude of the adjustments may be influenced by commonalities in ethnic and other backgrounds of the countries involved. Quarterly Review ofEconomics & Finance, Fall 1994,34(3): 241-259. (Reprinted with permission of ABUInform, Copyright UMI.)
Selling Leasehold Interests as a Means to Raise Capital
Authors: Leupold John
Published: July 2003

By using a unique and innovative structure to secure capital, property owners may be able to make deals that otherwise could not get done or finance more traditional deals in a much more timely and cost effective manner. This alternative financing structure enables owners to obtain capital by selling only some interest in a lease rather than obtaining traditional debt financing. A leasehold capital source (leaseholder) advances funds to the owner upon acquiring a portion of or all of the net income stream of a specific pattern and magnitude of the adjustments may be influenced by commonalities in ethnic and other backgrounds of the countries involved. Quarterly Review ofEconomics & Finance, Fall 1994,34(3): 241-259. (Reprinted with permission of ABUInform, Copyright UMI.)
The Financial Services Revolution
Authors: Kahl Douglas , Kahl Douglas
Published: July 2003

NA
Population pharmacokinetics of intramuscular gentamicin administered to young infants with suspected severe sepsis in Kenya
Authors: Thomson Alison H. , Kokwaro Gilbert O. , Muchohi Simon N. , English Michael , Mohammed Shebbe , Edwards Geoffrey
Published: July 2003

Aims  To determine the population pharmacokinetics of intramuscular (i.m.) gentamicin in African infants with suspected severe sepsis.

Methods  Samples were withdrawn 1 h after a single i.m. injection of 8 mg kg−1 gentamicin and the next morning prior to any further dosing. Concentration‐time data were analysed with the population pharmacokinetic package NONMEM. Data were fitted using a one‐compartment model with a log‐normal model for interindividual variability and an additive residual error model. The influence of a range of clinical characteristics was tested on the pharmacokinetics of intramuscular gentamicin and the effect of incorporating interindividual variability on bioavailability was examined.

Results  The data set comprised 107 patients and 203 concentrations. Peak concentrations ranged from 3.0 mg L−1 to 19.8 mg L−1 (median 10.6 mg L−1) and ‘next day’ samples from 0.3 mg L−1 to 6.2 mg L−1.The best models were clearance/bioavailability (CL) (L h−1) = 0.0913 × weight (kg) × (age (days) + 1)/11)0.130 and volume of distribution/bioavailability (V) = 2.02 × (1 + 0.277 × (weight −3)). Therefore, an infant with the median weight of 3 kg and age 10 days would have a predicted CL of 0.274 L h−1 and V of 2.02 L. Interindividual variability in CL was 40% and in V was 42%. This model required a term for covariance between CL and V. When variability in bioavailability was introduced as an alternative model, interindividual variability in CL was 22%, in V 18% and in relative bioavailability 36%.

Conclusions  Intramuscular administration of 8 mg kg−1 gentamicin daily to infants gives mean 1 h peak concentration of 10.6 mg L−1 and a trough concentration of less than 2 mg L−1. Wide variability in the peak concentration may reflect variable absorption rate or bioavailability.
Development of a dosing strategy for enoxaparin in obese patients
Authors: Green Bruce , Duffull Stephen B.
Published: July 2003

Aims  Enoxaparin dosing is currently based on total body weight. It is not known how to dose adjust for patients who are overweight or obese. This population pharmacokinetic pharmacodynamic (PKPD) study was undertaken to determine a suitable dosing strategy for such patients.

Methods  Patients admitted to the Royal Brisbane Hospital and prescribed enoxaparin as part of their normal care were eligible for inclusion into the study. Approximately three blood samples were taken per patient to determine anti‐Xa concentrations. The occurrence of bruising was also recorded. A population pharmacokinetic–pharmacodynamic analysis using NONMEM was undertaken. Simulations were performed using MATLAB.

Results  Ninety‐six patients were recruited in a prospective study. One‐third of patients had a body mass index < 24.9 kg m−2, one‐third from 25 to 29.9 kg m−2, and one‐third> 30 kg m−2. A two‐compartment linear model with additive error was fitted to the data. A covariate analysis showed clearance was best described by lean body weight and the central volume compartment by total body weight. The probability of bruising using a logistic regression model was best described by Cmax and age. Simulations suggest that patients over 50 years of age whose total body weight is> 90 kg, or under 50 years of age whose total body weight is> 120 kg are likely to have a smoother concentration–time profile and less bruising if a dose of 100 IU kg−1 (1 mg kg−1) based on lean body weight is administered every 8 h.

Conclusions  Dose adjustments of enoxaparin in obese patients are likely to reduce the prevalence of bruising, although prospective validation of this is required.
Asylum, children's rights and social work
Authors: Cemlyn Sarah , Briskman Linda
Published: July 2003

Although it is only a minority of displaced and persecuted people globally who seek refuge in ‘Western’ countries, they meet an increasingly hostile reception. This paper focuses on the situation facing children seeking asylum with or without their families in Britain and Australia, and the implications for children's rights and for social work. The policy background and its racist foundations in both countries are outlined. Despite geopolitical differences, there are unnerving parallels. Legislative changes and policy complexity signal increasingly punitive attitudes towards asylum seekers. The situation of children and families in the community is discussed in terms of the exclusion of asylum seekers from basic rights, and specific issues for separated children. Even more damaging is the incarceration of children and families in detention centres, and the emerging research is explored. In both countries there is widespread flouting of children's rights, and children also feature as pawns in ideological contests. However, they also act autonomously and illustrate an inclusive model of citizenship. The role of social workers in the statutory and voluntary sectors is considered, and the paper concludes with a discussion of the challenges for social work of avoiding collusion with repressive policies and actively promoting human rights.
The Colour of Difference: Journeys in Transracial Adoption
Authors: Thoburn June
Published: July 2003

Sarah Armstrong and Petrina Slaytor (eds)  The Federation Press, Sydney, 2001, 200 pp. AUS$33.95. ISBN 1 86287 397 6
Social work with African refugee children and their families
Authors: Okitikpi Toyin , Aymer Cathy
Published: July 2003

This article explores the issues and dilemmas that arise when social workers attempt to work with African refugee and asylum seeking children and their families. There is a complex interplay between social workers’ skills and knowledge in this area and the prevailing social attitudes towards these groups of service users. By initially setting the context of mass movement of peoples from situations of danger in their countries of origin, the discussion highlights the key issues and shows the tensions of practice intervention in this area. Drawing on a small‐scale research study with social workers and discussions with immigration officers and workers in voluntary agencies working with refugees and asylum seekers, the article draws some conclusions about the lessons that can be learnt in order to improve practice.
The social services response to unaccompanied children in England
Authors: Mitchell Fiona
Published: July 2003

In England, social services departments have a duty to provide care and protection to unaccompanied asylum seeking children from the point they arrive in the country. In recent years, research studies have identified a number of practice and policy issues of concern regarding the social services response to unaccompanied children. This paper focuses on three broad issues that emerge from the literature. The paper explores research concerns associated with (i) the referral and assessment process, (ii) the use of the child welfare legislative framework, and (iii) a number of issues arising from the provision of placements and other support offered to unaccompanied children. The findings of the research reviewed demonstrate that there are indeed clear grounds for concern. However, this paper argues that the evidence base is relatively weak and that as a result we know very little about the nature and context of the social work response to this group of children and young people.
Serum lipids in fathers and sons at middle age: the study of sons to men born in 1913
Authors: Rosengren A. , Eriksson H. , Welin C. , Welin L.
Published: July 2003

Abstract. Rosengren A, Eriksson H, Welin C, Welin L (Sahlgrenska University Hospital/Östra, Göteborg; and Lidköpng Hospital, Lidköping; Sweden). Serum lipids in fathers and sons at middle age: the study of sons to men born in 1913. J Intern Med 2003; 254: 126–131.

Objective. To relate lipid levels in middle‐aged men to that of their fathers at 50 years of age measured 30 years earlier.

Design and subjects. In 1963, 855 men born in 1913 took part in a cardiovascular risk factor survey when they were at 50 years of age. In 1993, 475 sons to these men, aged 44–56, were invited to another examination; 263 of these men were examined (response rate: 56%) and compared with their 217 fathers when they were examined at 50 years of age in 1963. In the 1993 survey, 798 men aged 50, were also examined, from a general population sample of men born in 1943 (response rate: 55%).

Setting. City of Göteborg, Sweden.

Main outcome measures. Serum lipids in sons as a function of lipids in their fathers.

Results. Compared with the men born in 1913, both sons and men born in 1943 had lower mean serum cholesterol, but higher body mass index (BMI) and serum triglycerides. There was a significant relation between serum cholesterol in sons and their fathers (r = 0.25; P < 0.0001). Amongst sons to fathers in the highest cholesterol quartile (>6.9 mmol L−1), 37% had serum cholesterol above 6.5 mmol L−1, compared with 16% amongst sons to fathers in the lowest quartile (<5.7 mmol L−1) [adjusted odds ratio 3.73 (1.52–9.12)]. Sons to fathers with the highest serum cholesterol levels had slightly lower BMI; otherwise there was no relation between serum cholesterol in the father and any other lifestyle or biological risk factor in the sons. Serum triglyceride concentration in the father was unrelated to any variable in the son.

Conclusions. There was a moderately strong association between serum cholesterol concentration in fathers and sons at middle age. However, secular trends were also important in determining serum cholesterol concentrations in those born at a later period, indicating a major role of environmental factors.
Circulating soluble cytochrome c in liver disease as a marker of apoptosis
Authors: Ben‐Ari Z. , Schmilovotz‐Weiss H. , Belinki A. , Pappo O. , Sulkes J. , Neuman M. G. , Kaganovsky E. , Kfir B. , Tur‐Kaspa R. , Klein T.
Published: July 2003

Abstract. Ben‐Ari Z, Schmilovotz‐Weiss H, Belinki A, Pappo O, Sulkes J, Neuman MG, Kaganovsky E, Kfir B, Tur‐Kaspa R, Klein T (Beilinson and Golda Campuses, Rabin Medical Center, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, and In Vitro Toxicology Laboratory, Sunnybrook Women's College, Toronto, Canada) Circulating soluble cytochrome c in liver disease as a marker of apoptosis. J Intern Med 2003; 254: 168–175.

Objectives. To measure levels of soluble cytochrome c, a clinical marker of apoptosis in patients with liver disease; determine whether soluble cytochrome c is derived from the liver; and correlate soluble cytochrome c level with histology and disease activity.

Design. Laboratory research study with comparison group.

Setting. Liver Institute, at the Rabin Medical Center, Israel, and In Vitro Toxicology Laboratory, Canada.

Subjects. A total of 108 patients with liver disease and 30 healthy controls.

Interventions. Paired hepatic and portal vein samples were taken via the transjugular vein in patients after liver biopsy and transjugular intrahepatic portacaval shunt, and bile from patients with external biliary drainage. Soluble cytochrome c was measured with an enzyme‐linked immunosorbent assay in peripheral blood. Apoptotic cells in liver tissue were identified by morphological criteria and quantitated with the dUTP nick‐end‐labelling (TUNEL) assay.

Main outcome measures. Soluble cytochrome c level by type of liver disease by clinical and histological findings.

Results. Soluble cytochrome c concentration (mean 187.1 ± 219.5 ng mL−1) was significantly higher in patients with liver disease than in controls (39.8 ± 35.1 ng mL−1; P = 0.0001), with highest levels in the primary sclerosing cholangitis group (mean 1041.0 ± 2844.8 ng mL−1; P = 0.001). Cytochrome c levels were correlated with serum bilirubin, alkaline phosphatase, creatinine levels, necroinflammatory score and apoptotic index, but not with serum alanine aminotransferase and synthetic liver function tests. In the 16 paired samples, soluble cytochrome c level was higher in the hepatic (mean 267.9 ± 297.0 ng mL−1) than the portal vein (mean 169.2 ± 143.3 ng mL−1), and it was highly detectable in bile (mean 2288.0 ±4596.0 ng mL−1) (P = 0.001). Untreated patients with chronic viral hepatitis (B and C) had significantly higher levels (mean 282.8 ±304.3 ng mL−1) than treated patients (77.9 ± 35.8 ng mL−1; P = 0.001).

Conclusions. Soluble cytochrome c levels are increased in different types of liver disease. Soluble cytochrome c is probably derived from the liver and secreted into the bile. Levels correlate with the apoptotic index and are affected by antiviral treatment. Soluble cytochrome c may serve as a serum marker of apoptosis.
Temporal responses of Arabidopsis root architecture to phosphate starvation: evidence for the involvement of auxin signalling
Authors: AL‐GHAZI Y. , MULLER B. , PINLOCHE S. , TRANBARGER T. J. , NACRY P. , ROSSIGNOL M. , TARDIEU F. , DOUMAS P.
Published: July 2003

The ability of the root system architecture to respond to nutrient availability is a key adaptative behaviour allowing plants to cope with environmental conditions. On the basis of single time point comparisons, the response to phosphate deprivation was previously shown to involve both the primary and lateral roots of Arabidopsis. In this work, the temporal pattern of Arabidopsis root responses to phosphate starvation was investigated. Daily scanning of roots showed that changes in architecture were largely due to the alterations of time‐based growth parameters, namely a decrease in the elongation rate of the primary root opposed to an increase in the elongation rate of lateral roots and a decrease in the number of initiated lateral roots. In addition, another identified response was a decrease in the proportion of lateral roots showing early growth arrest. All these changes occurred within a short period of approximately 3 d. In addition, the root morphology comparison with the auxin‐resistant mutant axr4, the auxin‐treatment of phosphate‐starved plants and a limited transcriptome analysis supported the conclusion that auxin signalling was involved in the adaptive response of the root system architecture to phosphate deprivation.
A coupled model of stomatal conductance, photosynthesis and transpiration
Authors: TUZET A. , PERRIER A. , LEUNING R.
Published: July 2003

A model that couples stomatal conductance, photosynthesis, leaf energy balance and transport of water through the soil–plant–atmosphere continuum is presented. Stomatal conductance in the model depends on light, temperature and intercellular CO2concentration via photosynthesis and on leaf water potential, which in turn is a function of soil water potential, the rate of water flow through the soil and plant, and on xylem hydraulic resistance. Water transport from soil to roots is simulated through solution of Richards’ equation. The model captures the observed hysteresis in diurnal variations in stomatal conductance, assimilation rate and transpiration for plant canopies. Hysteresis arises because atmospheric demand for water from the leaves typically peaks in mid‐afternoon and because of uneven distribution of soil matric potentials with distance from the roots. Potentials at the root surfaces are lower than in the bulk soil, and once soil water supply starts to limit transpiration, root potentials are substantially less negative in the morning than in the afternoon. This leads to higher stomatal conductances, CO2assimilation and transpiration in the morning compared to later in the day. Stomatal conductance is sensitive to soil and plant hydraulic properties and to root length density only after approximately 10 d of soil drying, when supply of water by the soil to the roots becomes limiting. High atmospheric demand causes transpiration rates, LE, to decline at a slightly higher soil water content,θs, than at low atmospheric demand, but all curves ofLEversusθsfall on the same line when soil water supply limits transpiration. Stomatal conductance cannot be modelled in isolation, but must be fully coupled with models of photosynthesis/respiration and the transport of water from soil, through roots, stems and leaves to the atmosphere.
Light and temperature, but not UV radiation, affect chlorophylls and carotenoids in Norway spruce needles (Picea abies (L.) Karst.)
Authors: KIRCHGEßNER H.‐D. , REICHERT K. , HAUFF K. , STEINBRECHER R. , SCHNITZLER J.‐P. , PFÜNDEL E. E.
Published: July 2003

Concentrations of chlorophyll a/freshweight (Chl a FW) and photosynthetic pigments/chlorophyll a were studied during one growing season in the current year's (CYN) and last year's needles (LYN) from Norway spruce (Picea abies (L.) Karst.) grown under natural or close‐to‐natural climate. Climate regimes differed in photosynthetic active radiation (PAR), temperature (T) and UV‐B radiation. Pigments were not affected by UV‐B but most of the differences between climate regimes, and also seasonal variations within climate regimes, could be related to PAR and T. Generally, two types of response to climate were observed: firstly, pigments reacted primarily to PAR without marked sensitivity to T and exhibited slow response times (> 30 d), and, secondly, pigments were affected by the combined action of PAR and T and responded faster than 20 d. The Chl a FW and chlorophyll b/chloprophyll a ratio exhibited slow‐type response in CYN and fast‐type response in LYN. Higher amplitudes in CYN than in LYN were observed for the latter two parameters, which are known to be associated with levels of pigment–protein complexes. It is suggested that slow response in CYN ensures that the high investments in proteins in these needles occur only in response to longer‐lasting climate episodes.
The radish Rfo restorer gene of Ogura cytoplasmic male sterility encodes a protein with multiple pentatricopeptide repeats
Authors: Brown Gregory G. , Formanová Nataša , Jin Hua , Wargachuk Richard , Dendy Charles , Patil Prashant , Laforest Martin , Zhang Jinfa , Cheung Wing Y. , Landry Benoit S.
Published: July 2003

A single radish nuclear gene, Rfo, restores Ogura (ogu) cytoplasmic male sterility (CMS) in Brassica napus. A map‐based cloning approach relying on synteny between radish and Arabidopsis was used to clone Rfo. A radish gene encoding a 687‐amino‐acid protein with a predicted mitochondrial targeting pre‐sequence was found to confer male fertility upon transformation into ogu CMS B. napus. This gene, like the recently described Petunia Rf gene, codes for a pentatricopeptide repeat (PPR)‐containing protein with multiple, in this case 16, PPR domains. Two similar genes that do not appear to function as Rfo flank this gene. Comparison of the Rfo region with the syntenic Arabidopsis region indicates that a PPR gene is not present at the Rfo‐equivalent site in Arabidopsis, although a smaller and related PPR gene is found about 40 kb from this site. The implications of these findings for the evolution of restorer genes and other PPR encoding genes are discussed.
Prostaglandin E1‐effective, transient‐type ischemic colitis developed after surgical resection of sigmoid colon cancer. A case report
Authors: ISHIHARA YUKAKO , SEIKE MASAHIRO , YOKOUCHI ITARU , SUDA HIROAKI , ISHITSUKA SHUNICHIRO , KAKEMURA TADAYOSHI , YOSHIDA MITSUHIRO , YOSHIMOTO KAZUYA , SAKAI YOSHIHIRO , OKUMURA CHIDORI , SAIDA YOSHIHISA
Published: July 2003

A 55‐year‐old‐man had a laparoscopic resection of the sigmoid colon due to colon cancer with submucosal invasion. After the surgery he suffered ileus and had a laparotomy. Six months later he complained of frequent defecation. Colonoscopy confirmed a circular ulcer extending from the anal side of the anastomosis in the sigmoid colon to the mid rectum. Endoscopic ultrasound demonstrated thickening of all layers of the diseased colon and rectum. We diagnosed ischemic colitis. After intravenous drip infusion of prostaglandin, symptoms and colonic stricture gradually improved. Although abdominal angiography revealed a narrowing of the peripheral sigmoid branch of the inferior mesenteric artery, blood flow was unrestricted. Colonoscopy performed 84 days after discharge revealed an ulcer scar.
Profiles of matrix metalloproteinases and their tissue inhibitors in intraperitoneal drainage fluid: Relationship to wound healing
Authors: Baker Elizabeth A. , Leaper David J.
Published: July 2003

Matrix degradation and remodeling occurs during wound healing, thereby aiding tissue repair, angiogenesis, and cell migration. It is dependent on the balance between proteinases and their inhibitors, namely the matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Acute wound fluid samples (n = 58 patients) were collected daily from the intraperitoneal drain placed after colorectal surgery from the first postoperative day until drain removal. Three laboratory techniques were performed: enzyme linked immunosorbent assays (MMP‐1, MMP‐3, TIMP‐1, TIMP‐2), gelatinase activity assays (MMP‐2, MMP‐9), and quenched fluorescent substrate hydrolysis (total MMP activity). Levels were correlated with each postoperative day, wound healing, and surgical outcome (p < 0.05, Spearman's correlation). Significant negative (MMP‐9, MMP‐3, MMP‐8, TIMP‐2, total MMP activity) and positive (MMP‐2, TIMP‐1) correlations were observed with the postoperative day, e.g., total MMP‐9: day 1, median, 121 (range, 12–189) ng/ml; day 3, 46 (8–179); day 5, 31 (0–155), day 7, 20 (6–58). Differences were also observed with the type of operation, estimated blood loss, and length of operation and with postoperative complications. MMPs and TIMPs are involved in wound healing after elective colorectal cancer surgery and their levels in drain fluid may act as markers of wound healing and surgical outcome. (WOUND REP REG 2003;11:268–274)
The oral immunogenicity of BioProtein, a bacterial single-cell protein, is affected by its particulate nature
Authors: Christensen Hanne R. , Larsen Linea C. , Frøkiær Hanne
Published: July 2003

The bacterial single-cell protein BioProtein (BP; Norferm Danmark, Odense, Denmark), produced by fermentation of natural gas with methanotrophic bacteria, is a potential protein source for man and animals. For human consumption, removal of the nucleic acid is necessary. Preliminary studies have shown that ingested BP induces a specific immune response. The objective of the present study was to characterize the type of response, its development over time and product-related causative factors. Mice were fed with diets containing 60 g nucleic acid-reduced BP/kg, 240 g nucleic acid-reduced BP/kg, 240 g untreated BP (basic BP)/kg or 240 g casein/kg (control). In another study, mice were fed 240 g basic BP/kg, whole cell-free BP-culture homogenate or control diet. The immune response was monitored using an ELISA for BP-specific immunoglobulin in blood and BP-specific immunoglobulin A in blood and saliva. Ingested BP induced a steady specific mucosal and systemic immune response, characterized by a dose-dependent production of immunoglobulin and immunoglobulin A in blood and immunoglobulin A in saliva. Basic BP and nucleic acid-reduced BP induced identical responses. However, feeding mice BP-culture homogenate induced immunoglobulin A in saliva but there was no systemic response. The antibodies from BP-fed mice cross-reacted with BP-culture homogenate revealing the presence of the same antigenic components in the two products despite the different oral immunogenicity. Thus, ingestion of BP induces a persistent mucosal and systemic immune response of which the systemic response can be avoided by ingesting a BP preparation free of whole cells. This indicates the importance of the non-particulate constitution of single-cell protein products intended for human or animal consumption.
Restoration of the integrity of rat caeco-colonic mucosa by resistant starch, but not by fructo-oligosaccharides, in dextran sulfate sodium-induced experimental colitis
Authors: Moreau Noëlle M. , Martin Lucile J. , Toquet Claire S. , Laboisse Christian L. , Nguyen Patrick G. , Siliart Brigitte S. , Dumon Henri J. , Champ Martine M. J.
Published: July 2003

Butyrate is recognised as efficient in healing colonic inflammation, but cannot be used as a long-term treatment. Dietary fibre that produces a high-butyrate level when fermented represents a promising alternative. We hypothesised that different types of dietary fibre do not have the same efficiency of healing and that this could be correlated to their fermentation characteristics. We compared short-chain fructo-oligosaccharides (FOS) and type 3 resistant starch (RS) in a previously described dextran sulfate sodium (DSS)-induced colitis model. Seventy-two Sprague–Dawley rats received water (control rats) or DSS (50g DSS/l for 7d then 30g DSS/l for 7 (day 7) or 14 (day 14) d). The rats were fed a basal diet (BD), or a FOS or RS diet creating six groups: BD-control, BD-DSS, FOS-control, FOS-DSS, RS-control and RS-DSS. Caeco-colonic inflammatory injuries were assessed macroscopically and histologically. Short-chain fatty acids (SCFA) were quantified in caeco-colon, portal vein and abdominal aorta. At days 7 and 14, caecal and distal macroscopic and histological observations were improved in RS-DSS compared with BD-DSS and also with FOS-DSS rats. Caeco-colonic SCFA were reduced in FOS-DSS and RS-DSS groups compared with healthy controls. The amount of butyrate was higher in the caecum of the RS-DSS rats than in the BD-DSS and FOS-DSS rats, whereas distal butyrate was higher in FOS-DSS rats. Partially explained by higher luminal levels of SCFA, especially butyrate, the healing effect of RS confirms the involvement of some types of dietary fibre in inflammatory bowel disease. Moreover, the ineffectiveness of FOS underlines the importance of the type of dietary substrate.
Effects of dietary conjugated linoleic acid on fatty acid composition and cholesterol content of hen egg yolks
Authors: Szymczyk Beata , Pisulewski Paweł M.
Published: July 2003

The main objectives of the present study were to determine the effect of dietary conjugated linoleic acid (CLA) isomers on the fatty acid composition and cholesterol content of egg-yolk lipids. Forty-five 25-week-old laying hens were randomly distributed into five groups of nine hens each and maintained in individual laying cages, throughout 12 weeks of the experiment. They were assigned to the five treatments that consisted of commercial layer diets containing 0, 5, 10, 15 or 20g pure CLA/kg. Feed intake of hens varied little and insignificantly. Egg mass was uniformly lower (P<0·05) in the hens fed the CLA-enriched diets. Feed conversion efficiency, when expressed per kg eggs, was impaired (P<0·05), although without obvious relation to the dietary CLA concentration. Feeding the CLA-enriched diets resulted in gradually increasing deposition of CLA isomers (P<0·01) in egg-yolk lipids. Saturated fatty acids were increased (P<0·01) and monounsaturated fatty acids decreased (P<0·01). Polyunsaturated fatty acids (PUFA), when expressed as non-CLA PUFA, were also significantly decreased (P<0·01). The most striking effects (P<0·01) were observed for palmitic (16 : 0) and stearic (18 : 0) acids, which increased from 23·6 to 34% and from 7·8 to 18%, respectively. On the other hand, oleic acid (18 : 1n-9) decreased from 45·8 to 24·3%. Among non-CLA PUFA, linoleic (18 : 2n-6) and α-linolenic (18 : 3n-3) acids were strongly (P<0·01) decreased, from 14·2 to 7·7% and from 1·3 to 0·3%, respectively. The same was true for arachidonic (20:4n-6) and docosahexaenoic (22 : 6n-3) acids. The cholesterol content of egg yolks, when expressed in mg/g yolk, was not affected by the dietary CLA concentrations. In conclusion, unless the adverse effects of CLA feeding to laying hens on the fatty acid profile of egg yolks are eliminated, the CLA-enriched eggs cannot be considered functional food products.
Lymphatic absorption of plasmalogen in rats
Authors: Hara Hiroshi , Wakisaka Takuya , Aoyama Yoritaka
Published: July 2003

Plasmalogen is a subclass of phospholipids that is widely distributed in man and animals. Many physiological roles have been proposed for this lipid; however, there have been no reports on the intestinal absorption of plasmalogen. In the present study, we examined lymphatic absorption of plasmalogen after the duodenal infusion of emulsified brain phospholipids (BPL) containing plasmalogen (22 mol% of total phospholipids) and soyabean lecithin (SPL) (100 g emulsified phospholipid/l). Male Wistar rats with implanted cannulas in the mesenteric lymph duct and the duodenum were kept in a Bollman-type restraining cage, and were infused the emulsion after 1 d recovery with duodenal infusion of a glucose–NaCl solution. Lymphatic plasmalogen output was increased at 2–4 h after the switch to BPL emulsion, and peaked at 4–6 h. However, no increases were observed after SPL infusion. Lymphatic recovery of plasmalogen for 8 h was 198 nmol, which was 0·22 mol% of the total plasmalogen disappeared from the intestine. We did not detect any increases in long-chain fatty aldehydes, which are the degradation product of plasmalogen, either in the blood or the small intestine. We conclude that a small percentage but a significant amount of the plasmalogen was absorbed into the lymph.
Intake of nutrients from pasture by poultry
Authors: Walker Andrew , Gordon Sue
Published: July 2003

EC legislation requires the land to which free-range poultry have access to be ‘mainly covered with vegetation’, but the nature of this vegetation is not specified. In practice, most free-range land will be grass pasture. Modern poultry nutrition is a highly-developed science, and to house poultry in an environment in which they may consume an unknown quantity of vegetation, itself of unknown nutritive value, introduces uncertainty into a predictable system. In recent years the contribution of grazing to the nutrition of the birds has been considered negligible. However, birds on range appear to ingest a little grass, and therefore the quality of the pasture may affect their performance. If poultry consumed largely grass, then the nutritional value derived from it would be relatively poor. The grass would constitute a source of energy and fibre, but would make little contribution in terms of protein. The likely approach that poultry nutritionists would take is a precautionary one. They would need to know the full nutritive value of the pasture and the likely quantitative intake by the birds, and they would then make adjustments to feed formulations at what they considered to be a ‘safe’ level, in order to minimise the risks of impairing performance. A small (0–5) percentage contribution is probably the most that could be achieved, but given that feed accounts for about 70% of the variable costs of poultry production, such a contribution is economically important.