bluuebunny/crossref_metadata_2025 huggingface dataset:
Powdered green tea has antilipogenic effect on Zucker rats fed a high‐fat diet
Authors: Hasegawa Noboru , Yamda Norihiro , Mori Midori
Published: May 2003

The effect of powdered green tea on the lipid metabolism was studied in male Zucker rats fed a 50% sucrose diet containing 15% butter. The oral treatment of 130 mg powdered green tea per day depressed body weight increase and various adipose tissue weights but food intake was unaffected. The treatment also slightly increased the plasma triglycerides. These effects were likely mediated by the inhibition of lipogenesis in the adipose tissues. The experimental group had a higher concentration of liver total lipid, triglycerides and plasma protein, and lower liver weights than the controls. This may be due to lipid deposition in the liver because of the reduction in adipose tissue weights. It was found that powdered green tea lowered the plasma total cholesterol but liver total cholesterol was unaffected. The results indicate that the hypocholesterolemic activity of powdered green tea might be due to the inhibition of the synthesis of cholesterol in the liver. Copyright © 2003 John Wiley & Sons, Ltd.
Inhibitory activity of plant extracts on nitric oxide synthesis in LPS‐activated macrophages
Authors: Ryu Jae‐Ha , Ahn Hanna , Kim Ji Yeon , Kim Young‐Kyoon
Published: May 2003

Nitric oxide (NO) produced in large amounts by inducible nitric oxide synthase (iNOS) is known to be responsible for the vasodilation and hypotension observed in septic shock and inﬂammation. Inhibitors of iNOS, thus, may be useful candidates for the treatment of inﬂammatory diseases accompanied by overproduction of NO. We prepared alcoholic extracts of woody plants and screened the inhibitory activity of NO production in lipopolysaccharide (LPS)‐activated macrophages after the treatment of these extracts. Among 83 kinds of plant extracts, 23 kinds of extracts showed potent inhibitory activity of NO production above 60% at the concentration of 80 µg/ml. Some of potent extracts showed dose dependent inhibition of NO production of LPS‐activated macrophages at the concentration of 80, 40, 20 µg/ml. Especially, Artemisia iwayomogi, Machilus thunbergii, Populus davidiana and Populus maximowiczii showed the most potent inhibition (above 70%) at the concentration of 40 µg/ml. Inhibitory activity of NO production was concentrated to nonpolar solvent fractions (ethyl ether and/or ethyl acetate soluble fractions) of Artemisia iwayomogi, Machilus thunbergii and Morus bombycis. These plants are promising candidates for the study of the activity‐guided puriﬁcation of active compounds and would be useful for the treatment of inﬂammatory diseases and endotoxemia accompanying overproduction of NO. Copyright © 2003 John Wiley & Sons, Ltd.
Biological activity of some naturally occurring resins, gums and pigments against in vitro LDL oxidation
Authors: Andrikopoulos Nikolaos K. , Kaliora Andriana C. , Assimopoulou Andreana N. , Papapeorgiou Vassilios P.
Published: May 2003

Naturally occurring gums and resins with beneﬁcial pharmaceutical and nutraceutical properties were tested for their possible protective effect against copper‐induced LDL oxidation in vitro. Chios mastic gum (CMG) (Pistacia lentiscus var. Chia resin) was the most effective in protecting human LDL from oxidation. The minimum and maximum doses for the saturation phenomena of inhibition of LDL oxidation were 2.5 mg and 50 mg CMG (75.3% and 99.9%, respectively). The methanol/water extract of CMG was the most effective compared with other solvent combinations. CMG when fractionated in order to determine a structure–activity relationship showed that the total mastic essential oil, collofonium‐like residue and acidic fractions of CMG exhibited a high protective activity ranging from 65.0% to 77.8%. The other natural gums and resins (CMG resin ‘liquid collection’, P. terebinthus var. Chia resin, dammar resin, acacia gum, tragacanth gum, storax gum) also tested as above, showed 27.0%–78.8% of the maximum LDL protection. The other naturally occurring substances, i.e. triterpenes (amyrin, oleanolic acid, ursolic acid, lupeol, 18‐a‐glycyrrhetinic acid) and hydroxynaphthoquinones (naphthazarin, shikonin and alkannin) showed 53.5%–78.8% and 27.0%–64.1% LDL protective activity, respectively. The combination effects (68.7%–76.2% LDL protection) of ursolic‐, oleanolic‐ and ursodeoxycholic‐ acids were almost equal to the effect (75.3%) of the CMG extract in comparable doses. Copyright © 2003 John Wiley & Sons, Ltd.
Plasma lipoproteins in transport of silibinin, an antioxidant flavonolignan from Silybum marianum
Authors: Švagera Zdeněk , Škottová Nina , Váňa Petr , Večeřa Rostislav , Urbánek Karel , Belejová Marie , Kosina Pavel , Šimánek Vilím
Published: May 2003

To assess the role of plasma lipoproteins in the transport of silibinin, an antioxidant ﬂavonolignan, 125I‐labelled silibinin (125I‐SB) administered perorally to the rat was used. The plasma 125I‐SB derived radioactivity was distributed among plasma lipoproteins according to their lipophilicity (TAG‐rich lipoproteins 30–40% > LDL 15% > HDL 5%), and in the fraction of d > 1.215 containing albumin and other proteins a minority amount of radioactivity was found. Administration of 125I‐SB in a complex with phosphatidylcholine resulted in proportionally higher radioactivities in all fractions as well as in tissues. Dietary olive oil had a slightly decreasing effect on plasma concentrations of silibinin measured by HPLC as well as on 125I‐SB derived radioactivity in plasma and liver. In the TAG‐rich lipoprotein fraction and HDL no effects of olive oil on the levels of 125I‐SB derived radioactivities were observed, however, at a 30 min interval the levels of 125I‐SB derived radioactivity in LDL and the heart were signiﬁcantly decreased in the olive oil group. These results suggest that (i) silibinin is not resorbed by the chylomicron pathway, and (ii) the endogenous lipoprotein pathway VLDL → LDL may play a role in the transport of silibinin from the liver to the extrahepatic tissues concurrently facilitating the lipoprotein antioxidant inﬂuence of silibinin. Copyright © 2003 John Wiley & Sons, Ltd.
Glycosmis arborea extract as a hepatoprotective agent
Authors: Gomes A. , Das M. , Sur P. , Besra S. E. , Chakravorty A. K. , Das B. , Ganguly D. K. , Vedasiromoni J. R.
Published: May 2003

Glycosmis arborea is a plant possessing various medicinal properties. The aim of the present study was to investigate the hepatoprotective efﬁcacy of the butanol extract obtained from the aerial parts of the plant. The test sample was prepared by extracting the material through different steps. The extract thus obtained was dissolved in normal saline. Albino rats were prophylactically treated with the extract (i.p.) for 3 weeks. At the end of 3rd week all the groups were injected with hepatotoxic agents. After 48 h of injection, blood was collected and livers were taken out. Different enzymes in the serum were assayed and histopathological study was performed with liver. Glycosmis arborea extract was able to overcome the toxic effects of hepatotoxic agents in terms of lowering the levels of serum GPT, alkaline phosphatase and increased level of SOD in serum. TBARS generation in liver was also altered. Moreover, necrosis of liver produced by carbon tetrachloride was reversed by the extract. Copyright © 2003 John Wiley & Sons, Ltd.
Cisplatin tumor concentrations after intra‐arterial cisplatin infusion or embolization in patients with oral cancer
Authors: Tegeder Irmgard , Bräutigam Lutz , Seegel Maic , Al‐Dam Ahmed , Turowski Bernd , Geisslinger Gerd , Kovács Adorján F.
Published: May 2003

Background

One neoadjuvant course of intra‐arterial high‐dose cisplatin (cis‐diamminedichloroplatinum [CDDP]) tumor perfusion combined with intravenous sodium thiosulfate (STS) (cisplatin neutralizer) infusion is part of a multimodality concept for treatment of oral cancer. Recently, crystalline cisplatin embolization has been described as a novel treatment variant with increased tumor response rates.

Methods

We have compared tumor and plasma concentrations of cisplatin and STS by means of microdialysis in 10 patients with oral cancer treated with intra‐arterial cisplatin perfusion (150 mg/m2 in 500 mL of 0.9% sodium chloride) and 6 patients with oral cancer treated with crystalline cisplatin embolization (150 mg/m2 in 45–60 mL of 0.9% sodium chloride), respectively. The microdialysis catheter was placed into the tumor, and the intra‐arterial catheter into the tumor‐feeding artery. Cisplatin was rapidly administered through the intra‐arterial catheter and STS (9 g/m2) was infused intravenously to reduce the systemic toxicity of cisplatin. STS infusion was started 10 seconds after the cisplatin infusion was started.

Results

After embolization, cisplatin tumor maximum concentration (Cmax) and tumor area under the concentration‐time curves (AUCs) were about 5 times higher than those achieved after intra‐arterial perfusion (Cmax, 180.3 ± 62.3 μmol/L versus 37.6 ± 8.9 μmol/L), whereas the opposite was true for plasma concentrations (Cmax, 0.9 ± 0.2 μmol/L versus 4.7 ± 0.6 μmol/L). STS plasma levels were about 3 times higher than its tumor concentrations (Cmax tumor, 1685 ± 151 μmol/L; Cmax plasma, 5051 ± 381 μmol/L). After the standard intra‐arterial perfusion, the average STS/CDDP AUC ratios for tumor and plasma were 211 ± 75 and 984 ± 139, respectively. After cisplatin embolization, the respective ratios were 48.5 ± 29.5 and 42,966 ± 26,728.

Conclusion

Molar STS/CDDP ratios of greater than 500 are required outside the tumor to neutralize cisplatin, whereas tumor ratios should be lower than 100 to avoid a loss of tumor cell killing. The first goal is achieved with both treatment modalities and the second only with cisplatin embolization, suggesting that crystalline cisplatin embolization is superior to intra‐arterial cisplatin perfusion in terms of tumor cisplatin concentrations. Whether this translates into higher tumor response rates needs to be investigated further.

Clinical Pharmacology & Therapeutics (2003) 73, 417–426; doi: 10.1016/S0009‐9236(03)00008‐0
Polymorphisms in the CYP1A2 gene and theophylline metabolism in patients with asthma
Authors: Obase Yasushi , Shimoda Terufumi , Kawano Tetsuya , Saeki Sachiko , Tomari Shin‐ya , Mitsuta‐Izaki Kazuko , Matsuse Hiroto , Kinoshita Moritoshi , Kohno Shigeru
Published: May 2003

Background

Cytochrome P450 (CYP) 1A2 gene polymorphisms are thought to be involved in theophylline metabolism.

Objective

We analyzed the effect of genetic polymorphisms in the 5′‐flanking region to the first intron of the CYP1A2 gene on theophylline metabolism in 75 Japanese patients with asthma and 159 healthy Japanese volunteers.

Methods

Genetic polymorphisms were detected at 4 sites of the CYP1A2 gene, −2964(G/A) and −1569(T/del) in the 5′‐flanking region and 155(T/G) and 731(A/C) in the first intron.

Results

There were no significant differences in the distribution of gene polymorphisms between the asthmatic and control groups. Among asthmatic patients, theophylline clearance was significantly lower in patients with the polymorphism at site −2964(G/A) whose genotype was G/A (0.029 ± 0.001 L · h−1 · kg−1) or A/A (0.029 ± 0.002 L · h−1 · kg−1) than in those whose genotype was G/G (0.034 ± 0.001 L · h−1 · kg−1) (P < .01 and P < .05, respectively). High theophylline clearance levels significantly correlated with age in the G/G subgroup of site −2964(G/A) (P < .05, r = −0.35) but not in the G/A or A/A subgroup.

Conclusion

Given its potential side effects, theophylline may need to be used with care in patients with the A allele at site −2964(G/A) in the CYP1A2 gene, because theophylline metabolism levels are lower in such patients, particularly in young asthmatic individuals.

Clinical Pharmacology & Therapeutics (2003) 73, 468–474; doi: 10.1016/S0009‐9236(03)00013‐4
Coordinated intrahepatic and extrahepatic regulation of cytochrome P4502D6 in healthy subjects and in patients after liver transplantation
Authors: Carcillo Joseph A. , Adedoyin Adedayo , Burckart Gilbert J. , Frye Reginald F. , Venkataramanan Raman , Knoll Carmela , Thummel Kenneth , Roskos Lorin , Wilson John W. , Sereika Susan , Romkes Marjorie , Bebia Zourab , Branch Robert A.
Published: May 2003

Cytochrome P450 (CYP) 2D6 activity exhibits wide intersubject variation even among individuals with similar genotypes in whom the active enzyme is expressed. There is, therefore, a need to understand the mechanisms involved in determining its activity. The relationship of messenger ribonucleic acid (mRNA) expression to CYP2D6 activity has been evaluated in hepatic and extrahepatic tissues to test the hypothesis of coordinated regulation. In human liver microsomes, there was a greater than 25‐fold variation in both bufuralol hydroxylation and concentration of mRNA for CYP2D6, with a significant association between variables (n = 20; Spearman correlation coefficient [rs] = 0.85, P < .001). In normal subjects, there was a similar extent of interindividual variation in in vivo activity of CYP2D6, measured as the debrisoquin (INN, debrisoquine) recovery ratio, and in mRNA for CYP2D6 in peripheral blood mononuclear cells, with a significant association between variables (n = 78; rs = 0.56 [95% confidence interval, 0.35 to 0.73],P < .001), whereas no association was found between mRNA for CYP2D6 and CYP2E1 activity. Recipients of liver transplants, at a time of stable liver function, had a similar relationship between debrisoquin recovery ratio and concentration of mRNA for CYP2D6 in peripheral blood mononuclear cells (n = 27; rs = 0.74 [95% confidence interval, −0.16 to 0.44], P < .001). Three recipients, who had CYP2D6*4/*4 genotypes, remained phenotypically poor metabolizers for CYP2D6 after liver transplantation. Collectively, these results imply that transcriptional regulation of mRNA for CYP is a major determinant of in vivo activity and that regulation of intrahepatic and extrahepatic enzymes is coordinated, possibly through a mechanism that is predominantly extrahepatic.

Clinical Pharmacology & Therapeutics (2003) 73, 456–467; doi: 10.1016/S0009‐9236(03)00055‐9
Individual differences in attachment–autonomy configurations: linkages with substance use and youth competencies
Authors: Lee Ji‐Min , Bell Nancy J.
Published: May 2003

Variations in attachment–autonomy configurations are explored as these relate to substance use and several adolescent competencies. Questionnaires completed by 470 university students included measures of parental attachment, autonomy (both emotional autonomy and self‐reliance), substance use, problems associated with substance use, social competencies, and coping. Analyses of subgroups representing four attachment–autonomy patterns, derived from cluster analysis, showed higher competency levels and fewer problems related to substance use for the group combining strong attachment and self‐reliance coupled with low levels of emotional autonomy. A subgroup characterized by low father but moderate mother attachment security differed in a number of ways from a subgroup reporting low attachment to both parents. Findings support the utility of a typological approach in investigations of adolescent attachment and autonomy.
Human papillomaviruses type 16+ and 18+ cervical carcinoma cells are sensitive to staurosporine‐mediated apoptosis
Authors: Bernard Benjamin , Prétet Jean‐Luc , Charlot Jean‐François , Mougin Christiane
Published: May 2003

Abstract We have recently shown that staurosporine (ST) can trigger apoptosis of CaSki and HeLa cervical tumor cells from G2/M checkpoint, though the mechanism remains elusive. In this study, we reported that ST induced the inhibition of E6 and E7 viral oncogene and MDM2 expression, while it led to increased levels of p53, which was transiently located to mitochondria. Additionally, the proteins of the p53‐regulated genes, p21WAF1 and Bax, were increased with a similar time, while Bcl‐2 and Bcl‐XL expression was lowered. Upon ST treatment, the cytochrome c was released into the cytosol and, then, activation of caspases‐9 and −3 led to Poly(ADP)RibosePolymerase (PARP) cleavage. Finally, characteristic morphological signs confirmed the apoptosis execution. Thus, taken together, all these observations suggest that apoptosis can be reactivated in HPV‐positive human carcinoma cells and highlight that ST could be used as a potently chemotherapy agent to enhance the sensitivity of tumor cells to apoptosis.
The effect on motor cortical neuronal development of focal lesions to the sub‐cortical white matter in the neonatal rat: a model for periventricular leukomalacia
Authors: Gibson Claire L. , Clowry Gavin J.
Published: May 2003

Periventricular leukomalacia (PVL) is either a diffuse or cystic lesion of the periventricular white matter that leaves the overlying cortical grey matter largely intact. It is believed to result from hypoxia occurring pre‐ or perinatally and is a major cause of cerebral palsy. We have modelled PVL in rats comparing the effects of discrete injections of 3‐nitropropionic acid (3‐NP), a mitochondrial toxin, ibotenic acid (IBA), a glutamate analogue, or saline into the sub‐cortical white matter on postnatal day 7 (P7). Following recovery times ranging from 3 days to 4 weeks, forebrain sections were Nissl stained or immunostained for Bax, cJun, calbindin (CB), parvalbumin (PV) or non‐phosphorylated neurofilaments (NPNF). Compared to saline injections, ibotenic acid caused large lesions of both grey and white matter not characteristic of periventricular leukomalacia. 3‐Nitropropionic acid injections caused small focal lesions restricted to the sub‐cortical white matter. 3‐Nitropropionic acid treatment initially increased expression of the apoptosis promoting proteins Bax and cJun, as well as non‐phosphorylated neurofilaments in cortical layer V overlying the injection site. Non‐phosphorylated neurofilament expression distal to the lesion was decreased representing a loss of cortical axons, but persisted and even increased with time within the cortex, demonstrating persistence of the parent cell bodies and local sprouting of neurites. There were significantly fewer calbindin and parvalbumin positive neurones in the motor cortex (MC) side ipsilateral to the 3‐nitropropionic acid injection compared to the contralateral side. These persistent differences in expression of activity sensitive calcium binding proteins suggest alterations in local cortical circuitry without substantial loss of grey matter as is characteristic of periventricular leukomalacia. Changes in expression of Bax, cJun and non‐phosphorylated neurofilaments during normal development are also described.
Antithrombotic therapy is associated with better survival in patients with severe heart failure and left ventricular systolic dysfunction (EPICAL study)
Authors: Echemann M. , Alla F. , Briançon S. , Juillière Y. , Virion J.M. , Mertès P.M. , Villemot J.P. , Zannad F. ,   EPICAL Investigators
Published: May 2003

Background:

In patients with congestive heart failure (CHF), clinical trials have demonstrated the benefit of a number of drugs on morbidity and mortality. Nevertheless so far, there is no published controlled study of long‐term antithrombotic therapy in patients with CHF. The aim of this work was to identify the relationship between cardiovascular drug use, especially antithrombotic therapy, and survival of CHF patients in current clinical practice, using an observational, population‐based database.

Methods:

The EPICAL study (Epidémiologie de l'Insuffisance Cardiaque Avancée en Lorraine) has identified prospectively all patients with severe CHF in the community of Lorraine. Inclusion criteria were age 20–80 years in 1994, at least one hospitalisation for cardiac decompensation, NYHA III/IV HF, ventricular ejection fraction ≤30% or cardiothoracic index ≥60% and arterial hypotension or peripheral and/or pulmonary oedema. A total of 417 consecutive patients surviving at hospital discharge were included in the database. The average follow‐up period was 5 years. Univariate Cox models were used to test the relationship of baseline biological and clinical factors to survival. Cardiovascular drug prescriptions were tested in a multivariate Cox model adjusted by other known predictive factors.

Results:

Duration of disease >1 year, renal failure, serum sodium ≥138 mmol/l, old age, serious comorbidity, previous decompensation, high doses of furosemide and vasodilators use were independently associated with poor prognosis at 1 and 5 years. Oral anticoagulants, aspirin, lipid lowering drugs and beta‐blockers use were associated with better survival. There was no interaction between aspirin and angiotensin converting enzyme inhibitor use on survival.

Conclusion:

Antithrombotic therapy was associated with a better long‐term survival in our study population of severe CHF. These results together with other previously published circumstantial evidence urge for a prospective, controlled and randomised trial specifically designed to evaluate optimal oral anticoagulants and aspirin in patients with congestive heart failure.
HLA alleles in isolated populations from North Spain: Origin of the Basques and the ancient Iberians
Authors: Sanchez‐Velasco P. , Gomez‐Casado E. , Martinez‐Laso J. , Moscoso J. , Zamora J. , Lowy E. , Silvera C. , Cemborain A. , Leyva‐Cobián F. , Arnaiz‐Villena A.
Published: May 2003

Abstract:  HLA‐A, ‐B, ‐DRB1, ‐DQA1 and ‐DQB1 alleles have been studied in three relatively isolated populations of northern Spain from Cantabria ( Pas Valleys inhabitants or Pasiegos and Cabuernigos) and from the Basque Country (Arratia Valley inhabitants). These populations have been compared with neighbouring ones and other Mediterraneans by using neighbour‐joining dendrograms and plane genetic distances.
α1 and α2 domains of Aotus MHC Class I and Catarrhini MHC Class Ia share similar characteristics
Authors: Suárez C.F. , Cárdenas P.P. , Llanos‐Ballestas E.J. , Martínez P. , Obregón M. , Patarroyo M.E. , Patarroyo M.A.
Published: May 2003

Abstract:  Functional and structural analyses of major histocompatibility complex (MHC) class I molecules of the Aotus genus are necessary to validate it as a solid animal model for biomedical research. We thus isolated, cloned and sequenced exons 2 and 3 from three Aotus species (A. nancymaae, A. nigriceps and A. vociferans). We found 24 sequences, which divided into two different groups (Ao‐g1 and Ao‐g2). A further sequence was identified as a processed pseudogene (Aona‐PS2). Both sequence evolution and variability analyses showed that Ao‐g1 and Ao‐g2 display similar characteristics to Catarrhini's classical loci, such as positive selection pressure at the peptide binding region (PBR) high variability and a trans‐specific evolution pattern.
Association of Fcγ receptor IIb and IIIb polymorphisms with susceptibility to systemic lupus erythematosus in Thais
Authors: Siriboonrit U. , Tsuchiya N. , Sirikong M. , Kyogoku C. , Bejrachandra S. , Suthipinittharm P. , Luangtrakool K. , Srinak D. , Thongpradit R. , Fujiwara K. , Chandanayingyong D. , Tokunaga K.
Published: May 2003

Abstract:  We recently reported association of a newly identified polymorphism of Fcγ receptor (FcγR) IIb, I232T, with systemic lupus erythematosus (SLE) in Japanese. To date, information on FcγR genotypes and their association with SLE is limited in South‐east Asian populations. To gain further insight into the role of FcγR polymorphisms in the genetic predisposition of SLE, association of FcγRIIa‐H131R, IIb‐I232T, IIIa‐F176V and IIIb‐NA1/NA2 (HNA‐1a/1b) polymorphisms with SLE was analyzed in the Thai population, using case–control association analysis. FcγRIIb‐232T/T and IIIb‐NA2/NA2 genotypes were associated with SLE with the odds ratio of 2.55. Genotype relative risk analysis revealed significant association of IIb‐232T/T and IIIb‐NA2/NA2, and a tendency of association of the IIIa‐176F/F genotype. Moreover, carriers of FcγRIIa‐131R were significantly increased in patients with lupus nephritis. Significant linkage disequilibrium was present among FcγRIIb, IIIa and IIIb, and two‐locus analyses suggested that the tendency of association of FcγRIIIa could derive from linkage disequilibrium with IIb and IIIb. These results provided evidence that FcγR polymorphisms may be an important predisposing factor also in Thais in a complex manner.
NKG2D ligands: unconventional MHC class I‐like molecules exploited by viruses and cancer
Authors: Cerwenka A. , Lanier L.L.
Published: May 2003

Abstract:  Our best teachers in revealing the importance of immune pathways are viruses and cancers that have subverted the most prominent pathways to escape from immune recognition. Viruses and cancer impair antigen presentation by classical MHC class I to escape adaptive immunity. The activating receptor NKG2D and its MHC class I‐like ligands are other recently defined innate and adaptive immune pathways exploited by viruses and cancer. This review discusses recent advances in the understanding of how NKG2D, expressed on innate immune cells including natural killer cells, γδ+ T cells and macrophages, and adaptive immune cells such as CD8+ T cells, recognize stress‐induced, MHC class I‐like, self‐ligands. Moreover, we describe how viruses and cancer have developed strategies to evade this recognition pathway.
Purification and partial characterization of a dipeptidyl peptidase from Prevotella intermedia
Authors: Shibata Y. , Miwa Y. , Hirai K. , Fujimura S.
Published: May 2003

A peptidase hydrolyzed X‐Pro‐p‐nitroanilide was purified from the cell extract of Prevotella intermedia ATCC 25611 by ion‐exchange chromatography and hydrophobic interaction chromatography. The purified enzyme exhibited a molecular size of 74 kDa from sodium dodecyl sulfate‐polyacrylamide gel electrophoresis and the maximum enzyme activity was found between pH 7.0 and pH 7.5. This peptidase was a serine enzyme and hydrolyzed Lys‐Pro‐p‐nitroanilide, Arg‐Pro‐p‐nitroanilide, and Ala‐Pro‐p‐nitroanilide, but Lys‐Ala‐p‐nitroanilide was not split. The enzyme may be classified as a dipeptidyl peptidase IV.
Detecting herbivore‐specific transcriptional responses in plants with multiple DDRT‐PCR and subtractive library procedures
Authors: Voelckel Claudia , T. Baldwin Ian
Published: May 2003

Differential display‐reverse transcriptase PCR (DDRT‐PCR) and subtractive hybridization with magnetic beads (SHMB) procedures were modified to compare the transcriptional responses of the postfire desert annual, Nicotiana attenuata when it is attacked by its two most abundant herbivores: the voracious Lepidopteran caterpillars of Manduca sexta and the piercing/sucking nymphs and adults of the mirid bug, Tupiocoris notatus. The relative merits of the two procedures were compared. DDRT‐PCR requires less starting material, allows for comparisons of multiple herbivores, and identifies both down‐ and up‐regulated responses, but is more laborious than SHMB. SHMB produced a greater proportion of known sequences (43.8 versus 35.6%), but the sequences were not significantly longer than those obtained by DDRT‐PCR, suggesting that the SMART (switching mechanism at 5′ end of RNA transcript) modification of the SHMB procedure did not produce the desired result. Both procedures produced apparent false positives and microarray‐based verification of differential expression would be a powerful approach to identify novel genes involved in ecological interactions. During the N. attenuata–T. notatus interaction, the expression of several photosynthesis‐related genes (cytochrome f, psaE, rubisco, rubisco activase, two aldolases, and phosphoglycerate kinase) was altered, which suggests that reprogramming of photosynthesis contributes to the mechanisms mediating tolerance to mirid damage. In addition, T. notatus‐induced changes in the expression of transcripts coding for a rhamnosyl transferase, a thionin, and an S‐adenosylmethionine‐decarboxylase are particularly interesting in the context of what is known about defence against herbivores in N. attenuata.
Self‐reported psychotic experiences in the general population: a valid screening tool for DSM‐III‐R psychotic disorders?
Authors: Hanssen M. S. S. , Bijl R. V. , Vollebergh W. , Van Os J.
Published: May 2003

Objective:   To examine the diagnostic value of self‐reported psychotic‐like experiences for DSM‐III‐R psychotic disorders.

Method:  A general population sample of 7076 subjects aged 18–64 years was interviewed with the Composite International Diagnostic Interview (CIDI) and, if there was evidence of psychotic experiences, the Structured Clinical Interview for DSM‐III‐R.

Results:  The probability of having a psychotic disorder increased in a dose–response fashion with the level of self‐reported psychotic experiences, but individual CIDI psychotic experience ratings had relatively low post‐test probabilities (PPs) (range: 5.1–26.5%). However, limiting the sample to individuals who had been in contact with mental health services substantially improved PPs (range: 13.3–43.1%).

Conclusion:  Screening for psychosis in the population carries a high risk of stigmatization in false‐positive cases and violation of the right ‘not to know’ in true‐positive cases. However, in mental health care users, self‐reported psychotic experiences may be a useful screening tool in individuals who have already developed help‐seeking.
Dimensional vs. categorical diagnosis in psychosis
Authors: Rosenman S. , Korten A. , Medway J. , Evans M.
Published: May 2003

Objective:  To compare dimensional measures vs. categorical diagnosis of psychopathology in their prediction of disability and outcome in psychotic illness.

Method:  A community study of 980 subjects with psychotic illness was included in the Australian National Survey of Mental Health and Wellbeing. The study instrument [including the Schedules for Clinical Assessment in Neuropsychiatry (SCAN)] yielded symptom data along with Operational Criteria for Psychotic Illness (OPCRIT) diagnoses by several diagnostic schemata. Factor analysis of symptoms yielded five dimensions of psychopathology (positive symptoms, negative symptoms, dysphoria, mania and substance use). Variance in service demand and disability explained by the diagnostic schemata was compared with the variance explained by the dimensions of psychopathology.

Results:  Dimensional measures of psychopathology explained more of the variance in service demand, dysfunctional behaviour, social adaptation and global occupation and function. Only use of support services and illness course were better predicted by categorical diagnosis. Dimensional scores explained significant extra variance when added to categorical diagnoses.

Conclusion:  Dimensional measures of psychopathology explain more variance in behaviour, disability and outcome than does categorical diagnosis in functional psychosis. Dimensions provided significant extra information not provided by diagnosis and would be a more useful basis for clinical management.
Apoptosis and transplantation tolerance
Authors: Chiffoleau Elise , Walsh Patrick T. , Turka Laurence
Published: May 2003

Summary:  Self‐tolerance is maintained by several mechanisms including deletion (via apoptosis) and regulation. Acquired tolerance to allogeneic tissues and organs exploits similar strategies. One key difference between alloantigens and peptide antigens is the enormous number of T cells that are alloreactive. Accumulating evidence suggests that in the face of this large mass of potentially graft‐destructive T cells, tolerance requires an initial wave of deletion. This creates a more level playing field in which a smaller number of regulatory T cells can then act to maintain an established tolerant state. Deletion of alloreactive T cells by apoptosis actively promotes immunoregulation as well, by interfering with proinflammatory maturation of antigen presenting cells. This article reviews the immune response to alloantigens, the development and use of both necrotic and apoptotic means of cell death during the evolution of the immune response, and the likely role and mechanisms by which apoptosis promotes, and may even be required for, transplantation tolerance.
The role of CD95 in the regulation of peripheral T‐cell apoptosis
Authors: Krueger Andreas , Fas Stefanie C. , Baumann Sven , Krammer Peter H.
Published: May 2003

Summary:  Apoptosis of activated peripheral T cells during the termination phase of an immune response is critical to maintain T‐cell homeostasis. Activated T cells can be removed by two mechanisms: activation‐induced cell death (AICD) and death by neglect. AICD is triggered by death receptors, whereas death by neglect is induced by cytokine withdrawal. CD95 (APO‐1/Fas) belongs to the subfamily of death receptors and plays a major role in AICD. In this review, we focus on the molecular mechanisms of AICD, in particular those involving the CD95 system. Moreover, we discuss the relative contribution of AICD and death by neglect to terminate a T‐cell immune response. In order to become fully activated, T cells require a second signal provided by antigen‐presenting cells. We discuss how these costimulatory signals counteract pro‐apoptotic signals and, finally, which signals might protect T cells from death to generate a pool of memory T cells.
Transducing signals from antigen receptors to nuclear factor κB
Authors: Ruland Jürgen , Mak Tak W.
Published: May 2003

Summary:  Signaling leading to the survival or apoptosis of immune system cells must be balanced to ensure the normal mounting and extinguishing of immune responses. One of the essential regulators of immune cell survival is the transcription factor nuclear factor κB (NF‐κB). NF‐κB is critical for the activation of T and B lymphocytes and is a central coordinator of innate and adaptive immunity. Pathogen recognition, whether mediated via the Toll‐like receptors or via the antigen‐specific T‐ and B‐cell receptors, initiates the activation of distinct signal transduction pathways that activate NF‐κB. Activation of NF‐κB by these pathways is necessary for lymphocyte activation, expansion, and effector function in response to infection. In addition, recent work has shown that the aberrant activation of NF‐κB by these pathways can contribute to the development of autoimmunity, chronic inflammation, or lymphoid malignancy. There is thus an urgent need to understand the exact molecular details of these signal transduction cascades so that we may develop novel therapeutics. This article will review the specific signal transduction pathways that mediate NF‐κB activation in response to antigen receptor ligation in T and B lymphocytes. These newly defined pathways, which are essential for adaptive immune responses, are built around the key adapter protein, Bcl‐10. Bcl‐10 is known to participate in chromosomal translocations in human mucosa‐associated lymphoid tissue lymphomas.
Crucified in the Mirror of Love: On Petrarch's Ambivalent Conception of Love in Rerum vulgarium fragmenta
Authors: Boysen Benjamin
Published: May 2003

In his Rerum vulgarium fragmenta, Petrarch demonstrates in a hitherto unseen manner how love is extremely ambiguous. Love is at one and the same time that which creates his identity, and that which dissolves it anew, it is simultaneously creation and destruction, recognition and alienation, pleasure and suffering – life and death. That is how (in the words of the brilliant Petrarch scholar Sara Sturm‐Maddox) his amorous subjectivity is profoundly ambiguous.1 The project of the poet is monological, and he strives toward a unity with himself, actualized in a circular and narcissistic auto‐communication in which he (so to speak) listens to his own speech – whereby he aims at being his own sender and recipient. But nevertheless he must concurrently affirm and negate the other, who mirrors the poet's self‐consciousness, but who contrarily alienates him as well. He has to express himself in the other in order to appear to himself which reluctantly makes the monological project dialogical. It is this fundamental, ambivalent conflict of poetry, which Petrarch eminently analyzes in his life's work. He has a strong inclination toward being solitary, unique, independent, and self‐enclosed, whereby he consequently objects the other to negation. However, he often emphasizes that self‐consciousness must make the detour by the other, if it is to achieve understanding and consciousness of itself. The purpose of this essay is to demonstrate that Petrarch's conception of love is ambivalent, and that it is due to the poet's special relation to the other, who is both conceived of as an opportunity and an obstacle to the manifestation of self‐consciousness, auto‐affection, and subjectivity.
Structures of the unspoken: the theatre of Nathalie Sarraute
Authors: Rothenberg John
Published: May 2003

Nathalie Sarraute's short intense plays dramatize the inner movements and emotions which she calls tropisms. There is no plot, no surface action in these works, and in this they typify an important trend in twentieth century theatre. The effect of these plays where nothing happens is far from static, however, and this article examines Le Silence and C'est beau to discover how this effect is achieved, how the author creates a variety of tension and a feeling of dramatic momentum. Using the actantial model first proposed by Souriau as an analytical tool it can be shown that within the basic situtation, which does not change, we have a series of microdramas, shifting alliances and conflicts. These are plays about what lies beneath the everyday, and they are structured to maintain a tension, sometimes comic sometimes cruel, between the surface and the depths.
A Subject After All – Rethinking the ‘personalized narrator’ of the self‐reflexive first‐person novels of O'Brien, Beckett and Banville
Authors: Pedersen Lene Yding
Published: May 2003

This essay suggests a way of getting beyond the ‘personalized’ narrator traditionally seen as defining the first‐person novel, without giving up completely the idea of an existential relationship between narrator and character. It explores the construction of a subject after all in three self‐reflexive first‐person novels (The Third Policeman, Malone Dies, Ghosts). These self‐reflexive first‐person novels cannot be explained within the existing framework of theories about the first‐person novel as they question and partly undermine the notion of the personalized narrator as a more or less unproblematic entity. To see how this subject is constructed in these self‐reflexive novels, this essay rethinks the ‘experiencing I’ and the ‘narrating I’ respectively in the light of Paul Ricoeur's concept of ‘narrative identity’ and Rimmon‐Kenan's concept of ‘access’. This leads to the notions of a ‘storied subject’ and a ‘speaking subject’. Furthermore it argues that we need to take into consideration a third aspect of the subject, the ‘linguistic subject’ (theoretically based on Benveniste) in order to comprehend the subject of the self‐reflexive first‐person novel.
Unconventional Myosins, Actin Dynamics and Endocytosis: A Ménage à Trois?
Authors: Soldati Thierry
Published: May 2003

Ever since the discovery of class I myosins, the first nonmuscle myosins, about 30 years ago, the history of unconventional myosins has been linked to the organization and working of actin filaments. It slowly emerged from studies of class I myosins in lower eukaryotes that they are involved in mechanisms of endocytosis. Most interestingly, a flurry of recent findings assign a more active role to class I myosins in regulating the spatial and temporal organization of actin filament nucleation and elongation. The results highlight the multiple links between class I myosins and the major actin nucleator, the Arp2/3 complex, and its newly described activators. Two additional types of unconventional myosins, myosinIX, and Dictyostelium discoideum MyoM, have recently been tied to the signaling pathways controlling actin cytoskeleton remodeling. The present review surveys the links between these three classes of molecular motors and the complex cellular processes of endocytosis and actin dynamics, and concentrates on a working model accounting for the function of class I myosins via recruitment of the machinery responsible for actin nucleation and elongation.
The relationship between insulin, IGF‐I and weight gain in cystic fibrosis
Authors: Taylor A. M. , Thomson A. , Bruce‐Morgan C. , Ahmed M. L. , Watts A. , Harris D. , Holly J. M. P. , Dunger D. B.
Published: May 2003

OBJECTIVE

In cystic fibrosis, reduced body mass is related to low levels of IGF‐I and changes in the IGF binding proteins. Our aim was to determine whether these abnormalities are linked to pancreatic endocrine dysfunction.

PATIENTS AND DESIGN

We measured serum levels of insulin, IGF‐I, IGFBP‐I, IGFBP‐3 and IGF bioactivity in 77 fasting subjects (43 male) mean age 9.6 years (range 2.99–17.98 years). Data were analysed with respect of body mass, puberty and stature and compared with control data established in the same laboratory.

RESULTS

The mean height standard deviation score (SDS (SD)) was −0.54 (0.97) and the body mass index SDS −0.24 (1.09). Both body mass index SDS (r = −0.40, P = 0.0003) and IGF‐I SDS (r = − 0.32, P = 0.009) declined with age. Insulin levels were also low and correlated with IGF‐I and IGFBP‐3 (r = 0.42, P = 0.0004, and r = 0.45, P = 0.0002, respectively) whereas levels of IGFBP‐I were inversely related to those of IGF‐I and insulin (r = − 0.43, P = 0.0004, r = − 0.52, P < 0.0001). IGF bioactivity was reduced and inversely related to IGFBP‐I (r = − 0.31, P = 0.009). In multiple regression analysis, body mass index SDS was negatively related to age (P < 0.0001) and positively related to insulin and IGF‐I (P = 0.04, P = 0.03, respectively). Height SDS was correlated with IGF bioactivity (P = 0.003) and negatively with IGFBP‐I (P = 0.01).

CONCLUSIONS

We conclude that progressive insulin deficiency may result in reduced IGF‐I levels and IGF‐bioactivity and may determine weight gain and statural growth in cystic fibrosis.
Relationship between ovarian cortisol:cortisone ratios and the clinical outcome of in vitro fertilization and embryo transfer (IVF‐ET)
Authors: Michael Anthony E. , Collins Tracey D. , Norgate Dean P. , Gregory Linda , Wood Peter J. , Cooke Brian A.
Published: May 2003

OBJECTIVE

Previously, we have reported an association between low levels of intraovarian cortisol metabolism, mediated by 11β‐hydroxysteroid dehydrogenase (11βHSD), and the establishment of pregnancies by in vitro fertilization and embryo transfer (IVF‐ET). The objective of the present study was to investigate the relationship between the clinical outcome of IVF‐ET and the intraovarian concentrations of cortisol and cortisone and the cortisol:cortisone ratios in random samples of ovarian follicular fluid (FF).

DESIGN

Retrospective, double‐blind correlation analyses.

PATIENTS

FF samples (n = 41) were obtained from 23 women undergoing gonadotrophin‐stimulated IVF‐ET cycles at the Cardiff Assisted Reproduction Unit.

MEASUREMENTS

Clinical pregnancy was confirmed by ultrasonography. Intrafollicular steroid concentrations were measured by radioimmunoassays.

RESULTS

Concentrations of both cortisol and cortisone were significantly lower in FF samples obtained from 6 patients that conceived than in samples obtained from 17 patients that did not achieve pregnancy (cortisol (mean ± SEM) = 304 ± 29 vs. 407 ± 26 nmol/l, P = 0.0411; cortisone = 32 ± 3 vs. 65 ± 7 nmol/l, P = 0.0002). Intrafollicular cortisol:cortisone ratios were significantly higher in samples from conception cycles than in those samples obtained from nonconception cycles (9.7 ± 0.7 vs. 6.9 ± 0.5, respectively, P = 0.0060). Whereas 5 of 10 women with intrafollicular cortisol:cortisone ratios greater than the outcome‐independent mean of 7.7 became pregnant, only 1 of the 13 patients with intrafollicular cortisol:cortisone ratios < 7.7 conceived (χ2 = 5.247, P = 0.0220).

CONCLUSIONS

Concentrations of both cortisol and cortisone were significantly lower in FF samples obtained from patients that conceived by IVF‐ET than in those obtained from nonconception cycles. Conception by gonadotrophin‐stimulated IVF‐ET was associated with an elevated intrafollicular ratio of cortisol:cortisone, consistent with a low level of intraovarian cortisol oxidation by 11βHSD.
Automated quantification and reconstruction of collagen matrix from 3D confocal datasets
Authors: Wu J. , Rajwa B. , Filmer D. L. , Hoffmann C. M. , Yuan B. , Chiang C. , Sturgis J. , Robinson J. P.
Published: May 2003

The geometrical structure of fibrous extracellular matrix (ECM) impacts on its biological function. In this report, we demonstrate a new algorithm designed to extract quantitative structural information about individual collagen fibres (orientation, length and diameter) from 3D backscattered‐light confocal images of collagen gels. The computed quantitative data allowed us to create surface‐rendered 3D images of the investigated sample.
Daytime sleepiness during Ramadan intermittent fasting: polysomnographic and quantitative waking EEG study
Authors: Roky Rachida , Chapotot Florian , Benchekroun Majda Taoudi , Benaji Brahim , Hakkou Farid , Elkhalifi Hassan , Buguet Alain
Published: May 2003

During the lunar month of Ramadan, Muslims abstain from eating, drinking and smoking from sunrise to sunset. We reported previously that Ramadan provokes a shortening in nocturnal total sleep time by 40 min, an increase in sleep latency, and a decrease in slow‐wave sleep (SWS) and rapid eye movement (REM) sleep duration during Ramadan. During the same study, the effects of Ramadan intermittent fasting on daytime sleepiness were also investigated in eight healthy young male subjects using a quantitative waking electroencephalograph (EEG) analysis following the multiple sleep latency test (MSLT) procedure. This procedure was combined with subjective alertness and mood ratings and was conducted during four successive experimental sessions: (1) baseline (BL) 15 days before Ramadan, (2) beginning of Ramadan (R11) on the 11th day of Ramadan, (3) end of Ramadan (R25) on the 25th day of Ramadan, (4) recovery 2 weeks after Ramadan (AR). During each session, four 20‐min nap opportunities (MSLTs) were given at 10:00, 12:00, 14:00 and 16:00 h and were preceded by rectal temperature readings. Nocturnal sleep was recorded before each daytime session. Subjective daytime alertness did not change in R25 but decreased in R11 at 12:00 h, and subjective mood decreased at 16:00 h, both in R11 and R25. During the MSLT, mean sleep latency decreased by an average of 2 min in R11 (especially at 10:00 and 16:00 h) and 6 min in R25 (especially at 10:00 and 12:00 h) compared with BL. There was an increase in the daily mean of waking EEG absolute power in the theta (5.5–8.5 Hz) frequency band. Significant correlations were found between sleep latency during the MSLT and the waking EEG absolute power of the fast alpha (10.5–12.5 Hz), sigma (11.5–15.5 Hz) and beta (12.5–30 Hz) frequency bands. Sleep latency was also related to rectal temperature. In conclusion, Ramadan diurnal fasting induced an increase in subjective and objective daytime sleepiness associated with changes in diurnal rectal temperature.
Practicality of the Sleepstrip™ in postal screening for obstructive sleep apnoea
Authors: Hollingworth Linda , Tooby Mary , Roberts Deborah , Hanning Christopher D.
Published: May 2003

The SleepStrip™, a disposable screening device for the detection of obstructive sleep apnoea (OSA), which displays an estimated apnoea–hypopnoea index (AHISS) was posted, with instructions, to 48 patients referred for sleep study for suspected OSA. The patients subsequently underwent a cardiorespiratory sleep study from which the AHIE was derived. Thirty patients (63%) returned the SleepStrip™, the device displayed an AHISS in 22 patients (73%), of which 17 (57%) was deemed valid by the device. Twelve of the 30 patients who returned the SleepStrip™ had an AHIE ≥ 20 on the detailed sleep study. Of these, the SleepStrip™ recording was valid in seven of which only two had an AHISS ≥ 20. We concluded that the SleepStrip™ was not suitable for unsupervised postal screening for OSA.