bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of insulin on rat ovarian leptin expression by immunohistochemical staining
Authors: Kuscu Naci Kemal , Ozbilgin Kemal , Inan Sevinc , Giray Gulsen , Ceylan Evren , Koyuncu Faik
Published: December 2003

Aim:  Leptin and insulin may interact in regulating ovarian steroid synthesis. The objective of this study was to investigate immunohistochemical staining of leptin in normal rat ovarian tissues and in rats treated with insulin and insulin plus human chorinoic gonadotropin (hCG).

Methods:  Paraffin blocks of rat ovarian tissues from a previous study, in which 18 adult, female Wistar rats with an average weight of 250 g were divided into three groups to receive either saline solution, human insulin (2 U/day) or human insulin (2 U/day) plus hCG (4 U/day) for 4 weeks, were used in this study to compare the effects on leptin staining. The results were analysed using a semiquantitative scoring system, such as mild, moderate and strong.

Results:  No staining was observed in granulosa cells and theca interna cells of normal ovarian tissues. Theca externa cells had mild staining intensity (+), corpus luteum had moderate (+ +) and stroma had mild (+) staining intensity. Histological structure was impaired in the insulin group, luteinized cells had mild staining, there was no difference in other cell groups. Only theca externa cells of the developing follicles were stained in insulin plus hCG group, luteinized cells again had mild staining.

Conclusions: Besides damaging the rat ovarian structure, insulin reduced staining intensity of leptin in luteinized cells. Insulin may stimulate ovarian steroid synthesis not only through its own receptors, but also by acting on the leptin expression of these cells.
Changes in serum concentrations of tumor necrosis factor α and adhesion molecules in normal pregnant women and those with pregnancy‐induced hypertension
Authors: Matsubara Keiichi , Abe Emiko , Ochi Hiroshi , Kusanagi Yasuki , Ito Masaharu
Published: December 2003

Aim:  To study whether serum tumor necrosis factor α gene (TNFα) and adhesion molecule levels are indicators of the onset of pregnancy‐induced hypertension (PIH), we compared levels of these molecules between normal pregnant women and PIH patients from the first to the third trimester.

Methods:  We serially measured serum concentrations of TNFα, soluble intercellular adhesion molecule‐1 (sICAM‐1), soluble E‐selectin (sE‐selectin), soluble vascular cell adhesion molecule‐1 (sVCAM‐1) and soluble P‐selectin (sP‐selectin) using enzyme immunoassay kits in 10 normal pregnant women and 10 pregnant women who developed PIH late in gestation.

Results:  Serum TNFα, sICAM‐1 and sE‐selectin levels in PIH affected women were significantly higher from the first trimester compared with those in normal pregnancy. sVCAM‐1 and sP‐selectin levels were not significantly changed.

Conclusion:  Serum TNFα, sE‐selectin and sICAM‐1 levels might be effective indicators of the onset of PIH.
Prenatal diagnosis for placental steroid salfatase deficiency with fluorescence in situ hybridization: A case of X‐linked ichthyosis
Authors: Watanabe Takafumi , Fujimori Keiya , Kato Katsuhiko , Nomura Yasuhisa , Onogi Satoshi , Sato Akira
Published: December 2003

X‐linked ichthyosis (XLI) is a relatively common genetic disorder that occurs in about one in every 2000–6000 male births. Clinically, XLI is characterized by a generalized scaling of the skin, with large, polygonal, dark brown scale, and more prominent on the extensor aspects of the limbs. It is known that an undetectable maternal serum, unconjugated estriol, associated with placental steroid sulfatase (STS) deficiency, may be the cause of cause of XLI. In most case, STS deficiency is caused by a complete or partial deletion of the STS gene mapped on chromosome Xp22.3. We describe here the prenatal detection of a male fetus affected with STS deficiency as a result of an undetectable unconjugated estriol in the second‐trimester maternal serum screening. Microdeletion of the STS gene was confirmed by fluorescence in situ hybridization analysis of cultured amniotic fluid.
Post‐partum endomyometritis diagnosis and treatment: A review
Authors: Ledger William J.
Published: December 2003

Over the past 80 years, obstetrical treatment strategies devised to control current problems have resulted in the emergence of new types of infection. These, in turn, have caused modifications in diagnostic techniques and treatment specifics. Currently, the two most obvious changes influencing post‐partum infection care are shortened post‐partum hospital care, and the widespread use of intra‐partum antibiotics to prevent early onset Group B streptococcal sepsis in the newborn. In the present review, risk factors for post‐partum infection are delineated and strategies for prophylaxis and treatment are given.
A randomized controlled trial of mite allergen‐impermeable bed covers in adult mite‐sensitized asthmatics
Authors: Luczynska C. , Tredwell E. , Smeeton N. , Burney P.
Published: December 2003

Background  Mite‐allergic patients with allergic disease should benefit from avoiding mite allergens. Many physicians, however, are yet to be convinced that allergen avoidance can make a significant contribution to asthma management in these patients. Many allergen‐avoidance regimes include multiple measures of allergen reduction, but as mite exposure in the home is most likely to be greatest in bed dust, bedding is usually the first target for intervention.

Objective  This study selected adult patients considered to be most likely to benefit from avoiding mite allergens, namely diagnosed asthmatics, sensitized to house dust mites and exposed to mite allergen in their mattresses. Patients were randomized into a placebo‐controlled trial of the use of allergen‐impermeable bed covers for 12 months, without any other form of mite‐reduction measures.

Methods  Adults with asthma were selected from general practices and asthma clinics in south‐east London. Their serum IgE to mite allergens and allergen content of mattress dust samples were measured. Those with >0.70 kU/L mite‐specific IgE and >2 μg/g Der p 1 were randomized into active or placebo treatments. Information was collected on allergic symptoms and medication use and quarterly peak flow diaries were kept throughout the trial. Dog or cat allergic patients were excluded if they had a pet at home to which they were sensitized.

Results  The mean decrease in μg/g Der p 1 was 25.7 (95% CI 8.9, 74.1) in the active group and 4.5 (95% CI 1.8, 11.5) in the placebo group. Der p 1 concentrations in the active and placebo groups at the end of the trial were not significantly different. There was no effect on peak flow or asthma symptoms in a simple comparison of the treatment and placebo groups.

Conclusion  In this group of patients, mite allergen avoidance in the bed by the use of allergen‐impermeable bedding alone cannot be recommended as an effective way of relieving asthma symptoms.
Differential in vivo cytokine mRNA expression in lesional skin of intrinsic vs. extrinsic atopic dermatitis patients using semiquantitative RT‐PCR
Authors: Jeong C.‐W. , Ahn K.‐S. , Rho N.‐K. , Park Y.‐D. , Lee D.‐Y. , Lee J.‐H. , Lee E.‐S. , Yang J.‐M.
Published: December 2003

Background
A small subgroup of atopic dermatitis (AD) patients with normal serum IgE levels and without specific IgE sensitization has been termed ‘intrinsic type of AD’ (ADi) as a counterpart to the term ‘extrinsic type of AD’ (ADe). However, there are neither molecular markers nor clinically diagnostic tools for distinguishing between ADi and ADe.

Objective
The present studies were undertaken to clarify the pathogenesis and in vivo cytokine micromilieu of ADi patients in comparison with ADe patients.

Methods
We used semiquantitative RT‐PCR to investigate the expression of various cytokines and assessed the tissue eosinophil counts in skin biopsies from both types of AD patients.

Results
Although there was no significant difference of cellular infiltrates in the lesional skin between ADe and ADi patients, ADe had significantly increased tissue eosinophilia than ADi. Based on our RT‐PCR, the expression patterns of cytokines could be categorized into four groups. The first group includes IL‐5, IL‐13, and IL‐1β, whose levels of mRNA expression were higher in both types of AD patients than non‐atopic (NA) subjects, while ADe patients had even higher levels than ADi patients. The second group includes interferon‐gamma (IFN‐γ), IL‐12, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), IL‐4, and IL‐10, whose levels of mRNA expression were elevated in both types of AD patients without differences between ADe and ADi patients. The third group includes tumour necrosis factor‐alpha (TNF‐α), whose mRNA expression was more decreased in both types of AD patients than NA, and the fourth group includes IL‐6 and transforming growth factor‐beta (TGF‐β), which did not show any differences among the three groups.

Conclusion
These current data demonstrate that the expressions of cytokines IL‐5, IL‐13, and IL‐1β mRNA and the number of dermal infiltrating eosinophils are increased in ADe patients compared with ADi patients.
Mechanisms of severe asthma
Authors: Wenzel S.
Published: December 2003

The mechanisms behind the development of severe asthma are poorly understood. However, these patients disproportionately consume healthcare resources related to asthma. Severe asthma may develop over time, or may develop shortly after onset of the disease. The genetic and environmental elements that may be most important in the development of severe disease are poorly understood. Physiologically, these patients often have air trapping and airway collapsibility. The pathology demonstrates a heterogeneity of findings, including continued eosinophilic inflammation, an apparently different pathology, structural changes likely to be remodelling related, and predominant distal disease. Treatment remains problematic and likely will remain so until a better understanding of this disease develops.
Impact of sublingual immunotherapy on seasonal asthma and skin reactivity in children allergic to Parietaria pollen treated with inhaled fluticasone propionate
Authors: Pajno G. B. , Vita D. , Parmiani S. , Caminiti L. , La Grutta S. , Barberio G.
Published: December 2003

Background
Immunotherapy is a recognized treatment for allergic respiratory diseases.

Objective
To study the usefulness of immunotherapy in combination with optimal pharmacological therapy.

Methods
Thirty‐eight children (8–14 years) suffering from seasonal asthma±rhinoconjunctivitis due to Parietaria poorly controlled by anti‐allergic drugs treatment were selected. After randomization according to a double‐blind placebo‐controlled design they received active sublingual immunotherapy (15 children) or placebo (15 children) for 13 months combined with inhaled fluticasone twice a day during the pollen season. Eight children were taken as control, whereas all patients were instructed to take symptomatic drugs on need. Early and late skin response to the allergen were assessed in all patients before and after treatment. Drug and symptom scores, as well as visual analogue scores (VASs) and Parietaria pollen counts were assessed during the pollen season.

Results
Groups were well balanced for age, gender, early and late skin response before treatment. Four children dropped out, in one case in relationship with active sublingual immunotherapy (SLIT) administration. Chest and nose symptoms, as well as drug scores and VASs were significantly better in both the active or placebo SLIT+fluticasone (S+F) as compared to the control group (P between <0.001 and 0.043). Eye symptoms were significantly better in the active S+F group as compared to control (P=0.025). The VASs were significantly better in the active S+F group as compared to the placebo S+F group (P=0.037). The early skin response decreased significantly in the active S+F group (P<0.001), whereas the late skin response changed significantly in all groups, with an increase in the placebo+fluticasone group (P=0.019) and in the control group (P=0.037) and a decrease (P<0.0001) in the active S+F group.

Conclusion
The clinical efficacy of S+F is equal to that of fluticasone alone, but the addition of SLIT has effects also on non‐bronchial symptoms.
Type I allergy to elderberry (Sambucus nigra) is elicited by a 33.2 kDa allergen with significant homology to ribosomal inactivating proteins
Authors: Förster‐Waldl E. , Marchetti M. , Schöll I. , Focke M. , Radauer C. , Kinaciyan T. , Nentwich I. , Jäger S. , Schmid E.R. , Boltz‐Nitulescu G. , Scheiner O. , Jensen‐Jarolim E.
Published: December 2003

Background
Patients suffering from allergic rhinoconjunctivitis and dyspnoea during summer may exhibit these symptoms after contact with flowers or dietary products of the elderberry tree Sambucus nigra.

Objective
Patients with a history of summer hayfever were tested in a routine setting for sensitization to elderberry. Nine patients having allergic symptoms due to elderberry and specific sensitization were investigated in detail. We studied the responsible allergens in extracts from elderberry pollen, flowers and berries, and investigated cross‐reactivity with allergens from birch, grass and mugwort.

Methods
Sera from patients were tested for IgE reactivity to elderberry proteins by one‐dimensional (1D) and 2D electrophoresis/immunoblotting. Inhibition studies with defined allergens and elderberry‐specific antibodies were used to evaluate cross‐reactivity. The main elderberry allergen was purified by gel filtration and reversed‐phase HPLC, and subjected to mass spectrometry. The in‐gel‐digested allergen was analysed by the MS/MS sequence analysis and peptide mapping. The N‐terminal sequence of the predominant allergen was analysed.

Results
0.6% of 3668 randomly tested patients showed positive skin prick test and/or RAST to elderberry. IgE in patients' sera detected a predominant allergen of 33.2 kDa in extracts from elderberry pollen, flowers and berries, with an isoelectric point at pH 7.0. Pre‐incubation of sera with extracts from birch, mugwort or grass pollen rendered insignificant or no inhibition of IgE binding to blotted elderberry proteins. Specific mouse antisera reacted exclusively with proteins from elderberry. N‐terminal sequence analysis, as well as MS/MS spectrometry of the purified elderberry allergen, indicated homology with ribosomal inactivating proteins (RIPs).

Conclusion
We present evidence that the elderberry plant S. nigra harbours allergenic potency. Independent methodologies argue for a significant homology of the predominant 33.2 kDa elderberry allergen with homology to RIPs. We conclude that this protein is a candidate for a major elderberry allergen with designation Sam n 1.
High‐dose exposure to cat is associated with clinical tolerance – a modified Th2 immune response?
Authors: Hesselmar B. , Åberg B. , Eriksson B. , Björkstén B. , Åberg N.
Published: December 2003

Background
Allergen‐specific IgG4 antibodies, it is suggested, may be protecting against allergy development by blocking responses. Levels are proposed as a marker of modified Th2 response.

Objectives
To assess the levels of IgE, IgG1 and IgG4 antibodies to cat in relation to cat exposure, asthma and allergic diseases.

Methods
We studied a population‐based sample of 412 schoolchildren of 12–13 years of age. Parents of 402 children completed a questionnaire covering their child's medical history, the keeping of cats and other background data. Skin prick tests (SPTs) to common aeroallergens were performed in 371 of the children. Blood samples for the analyses of IgE, IgG1 and IgG4 antibodies were obtained from 309 of them.

Results
All children had an immune response to cat, predominantly of the IgG1 subclass. The levels of cat‐specific IgG1 and IgG4, but not IgE, were high in children currently keeping a cat. Children with asthma had increased levels of cat‐specific IgE and IgG1, and children with a positive SPT to cat also had increased IgG4. The presence of IgG4 was not associated with asthma or sensitization, unless there was a simultaneous production of IgE. Twenty‐five percent of the children had an immune response with only IgG4, and no IgE antibodies to cat. This group of children had the highest frequency of cat‐keeping, but a similar prevalence of asthma and allergy as those with neither IgE nor IgG4 antibodies to cat.

Conclusion
Cat‐keeping was associated with a modified Th2 response, producing IgG4 but not IgE antibodies. This immune response was not associated with an increased risk of asthma or allergy. However, the IgG4 antibodies did not directly mediate any protective effect.
Heterogeneity of FeNO response to inhaled steroid in asthmatic children
Authors: Buchvald F. , Eiberg H. , Bisgaard H.
Published: December 2003

Background
Nitric oxide in exhaled air is regarded as an inflammation marker, and may be used to monitor the anti‐inflammatory control from inhaled corticosteroids (ICSs). However, this response to ICSs exhibits a heterogeneous pattern.

Objective
The study aimed to describe the independent variables associated with the heterogeneity in the response of exhaled nitric oxide to ICSs.

Methods
Exhaled nitric oxide (FeNO), lung function, bronchial hyper‐responsiveness (BHR), specific IgE to common inhalant allergens, blood eosinophils, other atopic manifestations and variants in nitric oxide synthethase 1 (NOS1) gene were studied in a double‐blind, placebo‐controlled crossover comparison of budesonide (BUD) Turbohaler 1600 mcg daily vs. placebo in asthmatic schoolchildren.

Results
Forty children were included in the study from a screening of 184 asthmatic children with moderately persistent asthma, well controlled on regular BUD 400 mcg daily: 20 children with normal FeNO and 20 with raised FeNO. FeNO, BHR and forced expiratory volume in 1 s improved significantly after BUD 1600 mcg (BUD1600). However, FeNO after ICS treatment exhibited a Gaussian distribution and FeNO was significantly raised in 15 children. Allergy and BHR, but none of the other independent variables under study were significantly related to FeNO after BUD1600.

Conclusion
Exhaled nitric oxide exhibited a heterogeneous response to ICS in asthmatic schoolchildren. Allergy and BHR were driving FeNO level independently of high‐dose steroid treatment. This should be considered when using FeNO for steroid dose titration and monitoring of ICS anti‐inflammatory control in asthmatic children.
Suspected tartrazine‐induced acute urticaria/angioedema is only rarely reproducible by oral rechallenge
Authors: Nettis E. , Colanardi M. C. , Ferrannini A. , Tursi A.
Published: December 2003

Background
Tartrazine has been frequently linked to several diseases. However, a cause‐and‐effect role for tartrazine in these illnesses, especially in urticaria, has not always been established.

Objective
The aim of this study is to determine the incidence of intolerance to tartrazine among subjects who experienced an acute episode of urticaria/angioedema following the ingestion of a meal or a product containing this substance.

Methods
This was a retrospective study based on analysis of data of patients reported to have experienced episodes of urticaria and/or angioedema after ingesting meals or products containing tartrazine. At the first visit to the outpatients clinic, a careful anamnesis had been taken. Patients had then been submitted to the following diagnostic tests: IgE tests to common inhalant allergens and food allergens and a double‐blind placebo‐controlled challenge with tartrazine.

Results
A total of 102 subjects were enrolled in the study: 19 (18.6%) showed at least one relevant positive reaction to an IgE test for food allergy. Only one subject (1%) had reactions after ingestion of 5 mg of tartrazine, given on day 5. She did not have adverse reactions to placebo.

Conclusion
This study shows that the percentage of acute urticaria and/or angioedema induced by tartrazine is very low (1%). In view of our results, we suggest that all physicians with patients who have suffered adverse reactions that could be attributed to tartrazine should also carefully evaluate other possible causes.
Potentiation of allergic bronchoconstriction by repeated exposure to formaldehyde in guinea‐pigs in vivo
Authors: Kita T. , Fujimura M. , Myou S. , Ishiura Y. , Abo M. , Katayama N. , Nishitsuji M. , Yoshimi Y. , Nomura S. , Oribe Y. , Nakao S.
Published: December 2003

Background
Indoor formaldehyde (FA) might worsen allergies and be an underlying factor for the increasing incidence and severity of asthma; the exact mechanism, however, remains unclear.

Objective
The present study examined the effects of repeated exposure to FA on methacholine‐ and antigen‐induced bronchoconstriction in guinea‐pigs in vivo.

Methods
First, non‐sensitized guinea‐pigs were transnasally treated with 0.1 or 1.0% FA or saline three times a week for 6 weeks, and increasing concentrations of methacholine (50, 100, and 200 μg/mL) were inhaled at 5‐min intervals. Second, guinea‐pigs pre‐treated with transnasal administration of FA or saline using the same protocol were passively sensitized with anti‐ovalbumin (OA) serum 7 days before antigen challenge. Third, guinea‐pigs were actively sensitized with OA and pre‐treated with transnasal administration of FA or saline using the same protocol. The lateral pressure of the tracheal tube (Pao) was measured under anesthesia and artificial ventilation.

Results
The antigen‐induced increase in Pao in actively sensitized guinea‐pigs was significantly potentiated by FA exposure in a dose‐dependent manner. The dose–response curve of the methacholine‐induced increase in Pao in non‐sensitized guinea‐pigs or of the antigen‐induced increase in Pao in passively sensitized guinea‐pigs was not altered by FA exposure. Transnasal administration of FA significantly increased the serum anti‐OA homocytotropic antibody titre (IgG) as measured by the passive cutaneous anaphylaxis reaction in actively sensitized guinea‐pigs.

Conclusion
The results suggest that repeated exposure to FA worsens allergic bronchoconstriction through enhancing antigen sensitization.
Remodelling of the upper airways in allergic rhinitis: is it a feature of the disease?
Authors: Salib R. J. , Howarth P. H.
Published: December 2003

The traditional viewpoint that inflammation, owing to a genetic T‐helper type 2 (Th2)‐directed imbalance, is the cause of allergic rhinitis has meant that the potential coexistence of other genetic defects and the relevance of any airway remodelling changes to disease pathogenesis and persistence have received scant attention, and as such remain controversial areas. This is particularly so in view of the limited published work in this field, which has so far reported markedly conflicting findings. This review endeavours to outline what is known about the nature of the remodelling response within the upper airway in allergic rhinitis, in addition to highlighting specific areas where further research is warranted.
Polymorphisms of the interferon gamma and interleukin 10 genes in human brucellosis
Authors: Bravo M. J. , De Dios Colmenero J. , Alonso A. , Caballero A.
Published: December 2003

We genotyped 83 patients with brucellosis and 101 controls to determine the influence of polymorphisms of the interferon gamma (IFNG) and interleukin 10 (IL10) genes on protection against, or susceptibility to, human brucellosis and its complications. The results showed a significant increase in the IFNG +874A/A genotype in patients compared with controls (34% vs. 19%) (P = 0.023, odds ratio = 2.17, 95% confidence interval 1.05–4.51). No significant differences were detected in the frequency distribution of the IL10 genotypes between patients and controls. Similarly, no significant differences were observed in the genotype frequencies of either of the two cytokines between complicated and non‐complicated forms of brucellosis. Persons who are homozygous for the IFNG +874A allele may have a higher risk of contracting brucellosis.
HLA in Czech adult patients with autoimmune diabetes mellitus: comparison with Czech children with type 1 diabetes and patients with type 2 diabetes
Authors: Cerna M. , Novota P. , Kolostova K. , Cejkova P. , Zdarsky E. , Novakova D. , Kucera P. , Novak J. , Andel M.
Published: December 2003

Type 1 diabetes results from an autoimmune insulitis, associated with HLA class II alleles. The evidence about HLA allele association is not clear in patients diagnosed after 35 years of age. In this study we have analyzed HLA alleles of DQB1 and DRB1 genes by sequence specific primer (SSP)‐PCR technique in adult patients with disease onset after 35 years of age. Two hundred and eighty‐one patients were divided into three groups according to the insulin therapy, the level of C peptide (CP), and GAD antibodies (anti‐GAD). Group 1 (type 1 diabetes in adults) was characterized by CP less than 200 pmol/L and anti‐GAD more or less than 50 ng/mL (n = 80). All of them had insulin therapy within 6 months after diagnosis. Group 2 latent autoimmune diabetes mellitus in adults (LADA) was defined by a minimum 6‐month‐long phase after diagnosis without insulin therapy, and was characterized by CP more than 200 pmol/L and anti‐GAD more than 50 ng/mL (n = 70). Group 3 (type 2 diabetes) was characterized by CP more than 200 pmol/L and anti‐GAD less than 50 ng/mL (n = 131). None ever had insulin therapy. In group 1, there was increased frequency of DRB1*04 (45.0% vs. controls 14.1%, OR = 5.0,P < 0.0005) and DQB1*0302 alleles (43.3% vs. controls 11.1%, OR = 6.1,P < 0.00005). There was increased frequency of DRB1*03 and DQB1*0201, and decreased frequency of DQB1*0602 (3.3% vs. controls 20.2%), but it was not significant. In group 2, there was a significantly increased frequency of DRB1*03 only (50.0% vs. controls 21.2%, OR = 3.7,P < 0.05). Compared with children with type 1 diabetes and adults with type 2 diabetes (group 3), we conclude that the presence of predisposing DQB1 alleles in adults with type 1 diabetes decreases with the age, probably due to environmental factors. Only the DRB1*03, but not the DQB1 gene, becomes the main predisposing allele in LADA patients. These findings suggest that the presence of HLA‐DQB1*0302 identifies patients at high risk of requiring insulin treatment. Type 1 diabetes mellitus (DM) in children or adults may have partly different immunogenetic etiopathogenesis than LADA.
Cytokine gene single nucleotide polymorphisms and susceptibility to and prognosis in cutaneous malignant melanoma
Authors: Howell W. M. , Turner S. J. , Theaker J. M. , Bateman A. C.
Published: December 2003

Cutaneous malignant melanoma (CMM) is a potentially fatal malignancy in which exposure to UV light is the most important risk factor. Several lines of evidence suggest that CMM patients develop an immune response to their tumours, although, in most cases, anti‐tumour immune responses are insufficient to abrogate tumour development. Polymorphism in genes regulating the immune response and cell growth may result in increased susceptibility to and/or poorer prognosis in certain individuals. In this study, we addressed whether single nucleotide polymorphisms (SNPs) associated with differential expression of selected pro‐ and anti‐inflammatory cytokines and growth factors [interleukin (IL)‐1β−35 and −511, IL‐2 −330, IL‐4 −590, IL‐6 −174, IL‐8 −251, interferon (IFN)‐γ+874 and transforming growth factor (TGF)β1 +915] or as markers of candidate cytokine genes (IL‐12 +1188) are associated with susceptibility to or known prognostic indicators (e.g. initial tumour growth phase, Breslow thickness, mitotic count in vertical growth phase tumours, tumour regression) in CMM. One hundred and sixty‐nine British caucasian CMM patients and 261 controls were included in the study and all SNPs were genotyped by ARMS–PCR. No SNP genotypes or alleles showed significant associations with CMM susceptibility and only the IL‐1β−511 TT genotype was associated with thinner invasive tumours at presentation, as assessed by Breslow thickness at the clinically significant cut‐off point of 1.5 mm [occurring in 2/51 (3.9%) thicker vs. 14/78 (17.9%) thinner tumours (P = 0.03; relative risk = 0.29 (95% confidence interval 0.05–0.95)]. These findings suggest that — with the possible exception of IL‐1β— genetic variation associated with differential expression of the selected pro‐ and anti‐inflammatory cytokines is unlikely to play a major role in susceptibility to and prognosis in CMM.
Coeliac disease: investigation of proposed causal variants in the CTLA4 gene region
Authors: King A. L. , Moodie S. J. , Fraser J. S. , Curtis D. , Reid E. , Dearlove A. M. , Ciclitira P. J.
Published: December 2003

Coeliac disease (CD) is an immune‐mediated enteropathy triggered by gluten in genetically predisposed individuals. Patients with CD have an increased prevalence of other autoimmune disorders, including type 1 diabetes (T1D) and Graves’ disease (GD). CD shares with these conditions certain HLA susceptibility alleles. A number of studies have also shown association of autoimmune diseases, including CD, with the CD28‐cytotoxic T lymphocyte antigen 4 (CTLA4)‐inducible costimulator (ICOS) region of chromosome 2q33, but until recently the precise causal variant has remained unknown. Recently, it was shown that, in GD, CT60 (+6230G>A), a single nucleotide polymorphism (SNP) at the end of the CTLA4 transcript, is associated with an alteration in the ratio of splice forms of the CTLA4 gene and that this ratio affects disease susceptibility. A similar but weaker association was found with T1D. There is also an independent association of GD and T1D with the SNP MH30 (−23 327G>C), which possibly affects promoter region function.

Hypothesizing that CT60 and MH30 may be causal variants in other autoimmune disorders, we investigated these SNPs in CD using 149 family trios and 100 unrelated/unaffected controls. No association was detected with either SNP using both the transmission disequilibrium test (TDT) and case–control methods. Our study appears to have good power to detect moderate genetic effects, but possibly these SNPs exert too weak an effect on risk of CD to have been detected in our sample. Alternatively, the previously noted association of CD with the CTLA4 gene region may be due to different causal variants. Unlike T1D and GD, CD is not a true autoimmune disease, and CD has different associations at the CTLA4 exon 1 SNP +49G>A from all other autoimmune disorders. MH30, CT60, and other SNPs in the region may still warrant further investigation in other CD samples.
Effect of food shortage and temperature on oxygen consumption in the lesser mealworm, Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae)
Authors: Renault D. , Hervant F. , Vernon P.
Published: December 2003

Abstract.  Temperature and food availability are limiting factors for the establishment of tropical insects in temperate countries. In the alien pest beetle, Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae), starvation and temperature have a significant impact on metabolic rate with oxygen consumption ranging from 0.5 µmol/g fresh mass (FM)/h at 12 °C to 3.4 µmol/g FM/h at 24 °C. At 12 °C, oxygen consumption decreased continuously during an entire period of starvation. However, at 16, 20 and 24 °C, beetles display a marked hyperactivity that leads to an increase in the oxygen consumption level during the first week of starvation, followed by a steep decrease until the end of the starvation period. Oxygen consumption either does not decline in fed beetles (observed at higher temperatures) or declines at a much shallower rate than in starved beetles (observed at cooler temperatures). During the first week of refeeding, Oxygen consumption rose steeply at 16, 20 and 24 °C before levelling off to the initial value (t0). At 12 °C, no compensation process was observed during recovery. This study reveals that an important threshold in the biology of A. diaperinus lies between 12 and 16 °C, leading to the onset of reduced locomotor activity and the promotion of survival to the detriment of reproduction. This ‘sit and wait’ behaviour is proposed as an adaptive strategy (i.e. inactivity and lower oxygen consumption coupled with low energetic requirements and high recovery abilities). Such behaviour and the observed hyperactivity were rarely described in insects before the present study. Together, the previous and present results suggest that A. diaperinus populations are likely maintained in temperate regions by immigration from warmer situations.
Methyl 3‐chloro‐4‐methoxybenzoate, a new candidate semiochemical inhibiting copulation behaviour of Ixodes ricinus (L.) males
Authors: Bouman E. A. P. , Dusbábek F. , Šimek P. , Zahradníèková H.
Published: December 2003

Abstract.  Females of Ixodes ricinus (L. 1758) emit several semiochemicals influencing copulatory behaviour in males. One of these candidate compounds, methyl 3‐chloro‐4‐methoxybenzoate, is emitted exclusively by engorged females, and shows a copulation inhibiting effect in males. In Y‐tube experiments, the synthetic analogue of this compound at a concentration of 100 µg/mL in ethanol, attracted males in only 25.6% of tests, whereas it repelled them in 74.4% of cases. However, unengorged females do not respond to this substance at all. The number of contacts between males and unengorged females treated with methyl 3‐chloro‐4‐methoxybenzoate (250 µg/mL in ethanol, 1 µL per female) decreases to 28% compared to a control level of 80%, and the percentage of copulating pairs decreases to 12% compared to control (49%) over 2 h. Possibly, a fertilized engorged female with mature eggs uses this semiochemical to send a signal to males indicating that another copulation is no longer needed.
Ambient temperature and sound power of cicada calling songs (Hemiptera: Cicadidae: Tibicina)
Authors: Sueur Jérôme , Sanborn Allen F.
Published: December 2003

Abstract.  Male cicadas produce a loud calling song that attracts females at long range. In some cases, ambient temperature has been shown to have an effect on the temporal structure of this acoustic signal. Here, a positive correlation is reported for the first time between the ambient temperature and the sound power of the calling song. This relationship is illustrated in three species of the Palaearctic genus Tibicina: Tibicina corsica fairmairei Boulard, Tibicina garricola Boulard and Tibicina tomentosa Olivier. It is suggested that the males thermoregulate behaviourally. The minimal ambient temperature range that the Tibicina species need to call is 22–24 °C. The effect of ambient temperature on calling song power is assumed to be the result of thermal effects in the response of the acoustic system (i.e. muscle activity of the acoustic system being temperature‐dependent). Inter‐individual and interspecific differences in calling song power are interpreted in the general context of the Tibicina sound behaviour.
Optocardiographic recording of heart rate in Talitrus saltator (Amphipoda: Talitridae)
Authors: Calosi Piero , Chelazzi Guido , Ugolini Alberto
Published: December 2003

Abstract.  An optocardiographic non‐invasive technique was used to monitor heart activity in small arthropods. Heart rate was recorded in adult individuals of the supralittoral amphipod Talitrus saltator after 3 h of immersion in marine artificial water (0, 11 and 33‰, t = 15 ± 1 °C). Mean heart rate (± SE) ranged from 210 ± 26 beats min−1 (at 33‰) to 276 ± 15 beats min−1 (at 0‰) and, despite the small increase in temperature (0.5 °C) due to the infrared beam, the heart frequency remained constant for several hours. Neither the glue used to apply the sensor to the animal nor the beating of the pleopods affected heart rate. This technique could be a useful tool for the investigation of ecophysiological aspects in T. saltator, which is already well known for its ecology and behaviour.
Stem cells in paroxysmal nocturnal haemoglobinuria and aplastic anaemia: increasing evidence for overlap of haemopoietic defect
Authors: Marsh J. C. W. , Elebute M. O.
Published: December 2003

Summary.  The clinical association between paroxysmal nocturnal haemoglobinuria (PNH) and aplastic anaemia (AA) has long been recognized. Haemolytic PNH, as confirmed by a positive Ham's test, can occur in the setting of AA, and conversely AA can be a late complication of PNH. With the development of sensitive flow cytometry to quantify the expression of phosphatidylinositolglycan (PIG)‐anchored proteins on blood cells, a small PNH clone can now be detected in a large number of patients with AA at diagnosis. PIG‐A gene mutations can also be demonstrated in some AA patients. In haemolytic PNH, there is always marrow suppression despite a morphologically cellular marrow. In vitro cultures show markedly diminished proliferative capacity in both short‐term and long‐term marrow cultures, similar to that seen in AA. A similar autoimmune process, through the T‐cell cytotoxic repertoire, is probably responsible for the pathogenesis of both AA and PNH. PIG‐deficient cells may be resistant to immunological attack by autoreactive cytotoxic T cells, because they lack PIG. They are also more resistant to apoptosis than the PIG‐normal cell population. This results in the selection of the PIG‐deficient clone, in contrast to the PIG‐normal stem cells which possess the PIG anchor and hence are targeted and depleted by the autoreactive T cells.
New advances in acute graft‐versus‐host disease prophylaxis
Authors: Davies J. K. , Lowdell M. W.
Published: December 2003

Summary.  Immunocompetent donor T cells in Allogeneic Haematopoietic Stem Cell grafts mediate acute Graft versus Host Disease (GvHD), still a major cause of recipient morbidity and mortality post transplant. Despite the advent of high resolution HLA‐typing and matching at HLA loci, acute GvHD remains a significant problem, even in HLA matched siblings, due primarily to minor histocompatability antigen mismatches. Treatment of GvHD remains ineffective and highly immunosuppressive and the challenge to find effective methods of prevention continues. Non selective removal of donor T cells from the graft has been proven to be effective in preventing GvHD but the beneficial effects of donor T cells, namely effective immune reconstitution and anti tumour activity, are lost. This review considers mechanisms by which acute GvHD may be prevented in the context of the current model of GvHD immunopathogenesis, with a special emphasis on the recent techniques of selective removal or destruction of donor allogeneic T cells that have been described.
Natural killer cells in haematopoietic stem cell transplantation
Authors: Lowdell M. W.
Published: December 2003

Summary.  Natural killer cells represent the predominant lymphoid cell in the peripheral blood for many months after allogeneic or autologous stem cell transplant and their role in immunity to pathogens during this period is established. However, following the largely unsuccessful trials of NK and IL‐2 activated NK cells for the treatment of haematological malignancies in the 1980's and 90’s, their role in tumour immunology was discredited. Over the past ten years we have come to understand some of the complex regulatory pathways involved in NK cell activation and we are now in a position to capitalise upon this knowledge. This review presents our current state of understanding of NK cell regulation and highlights the role of these cells in engraftment, graft‐versus‐host disease, anti‐leukaemia activity and post‐transplant infection.
Formation and emplacement of the Dolodrook serpentinite body, Lachlan Orogen, Victoria
Authors: Spaggiari C. V. , Gray D. R. , Foster D. A.
Published: December 2003

Serpentinised peridotite and ultramafic breccia make up an approximately 5 km‐long, 1 km‐wide fault slice within turbidites in the Dolodrook River region of the central Lachlan Orogen. The serpentinite body is surrounded by juvenile, mafic–ultramafic sedimentary rocks with Cambrian limestone olistoliths representative of locally derived debris flows, and Middle to Upper Ordovician black shale, chert, sandstone and mudstone. The antiformal geometry and nature of the ultramafic breccia and mafic–ultramafic sedimentary rocks (Garvey Gully Formation) indicate that the serpentinite body may have been either a former oceanic transform fault zone, a Marianas‐style serpentine seamount or a combination of these. Observations of modern‐day forearc regions show that faulting processes have led to the exposure of serpentinised peridotite horst blocks and serpentine mud volcanoes that have intruded along fault conduits (e.g. Marianas and Izu–Bonin forearcs). At Dolodrook, the structural and metamorphic relationships with the surrounding rocks, and the lithological associations, have much in common with these observations and indicate that Dolodrook may be an ancient, on‐land example of an accreted seamount or oceanic topographic high. Structural relationships, the very low metamorphic grade of all rocks at Dolodrook, and the presence of broken formation developed in not‐fully lithified Middle to Upper Ordovician sandstone and mudstone indicate that the serpentinite body was emplaced at shallow crustal levels within the turbidite wedge (Tabberabbera Zone), possibly as an offscraped topographic high during marginal basin closure. The Dolodrook serpentinite has previously been inferred as part of the Cambrian igneous sequence (‘greenstones’) exposed in the Governor, Mt Wellington and Heathcote Fault Zones, but structural and metamorphic relationships with surrounding rocks, and the Cambrian tectonic setting in which it formed, have remained speculative.
Preoperative serum acid phosphatase and alkaline phosphatase are not predictors of pathological stage and prostate‐specific antigen failure after radical prostatectomy
Authors: San Francisco I.F. , Olumi A.F. , Yoon J.H. , Regan M.M. , DeWolf W.C.
Published: December 2003

OBJECTIVE

To examine the utility and prognostic significance of enzymatic serum acid phosphatase (total acid phosphatase, TAP, and prostatic fraction of acid phosphatase, PFAP) and alkaline phosphatase (ALP) for staging, grading and outcome of patients who underwent radical retropubic prostatectomy (RRP) after the introduction of prostate‐specific antigen (PSA) testing.

PATIENTS AND METHODS

In all, 180 consecutive patients with clinically localized prostate cancer who underwent RRP with standard obturator lymph‐node dissection between 1 January 1990 and 31 December 1995 were evaluated. Levels of TAP of > 5.4 IU/L, PFAP of > 1.2 IU/L and ALP of > 120 IU/L were classified as abnormally high. The relationship between abnormally high values and prostate cancer stage, grade and time to recurrence after RRP were calculated. The median follow‐up was 86 months (≈ 7 years).

RESULTS

Of the 180 patients, information about preoperative TAP, PFAP and ALP were available in 164, 163 and 154, respectively; TAP was abnormal in seven (4%), PFAP in 33 (20%) and ALP in only 13 (8%). None of the markers examined was associated with any variables of disease severity, as measured by pathological stage, Gleason score, perineural invasion, capsular penetration, positive margins, seminal vesicle involvement, and lymph node involvement. Abnormal TAP, PFAP or ALP were not associated with recurrence (P = 0.96, 0.45 and 0.41, respectively). In contrast, a PSA level of > 4 ng/mL was predictive of recurrence after RRP (P < 0.001). In the sample overall, 25 (14%) of the patients had recurrence and only one died from prostate cancer.

CONCLUSIONS

Preoperative enzymatic serum TAP, PFAP and ALP levels are not predictors of the severity of disease or PSA disease‐free recurrence after RRP.
Evolution of Poverty During the Crisis in Indonesia
Authors: Suryahadi Asep , Sumarto Sudarno , Pritchett Lant
Published: December 2003

The economic crisis caused a clear deterioration in the welfare of the Indonesian people. In this paper, we examine the appropriate method to compare the change in poverty rates over time. We then piece together a consistent series of estimates of poverty rates during the crisis from various sources, covering a period from February 1996 to February 2002. The reconciliation of these various estimates paints a very reasonable picture and neatly tracks events. The poverty rate increased from the lowest point of approximately 15% at the onset of the crisis in the middle of 1997 to the highest point of approximately 33% nearing the end of 1998. This maximum increase in poverty rate during the crisis of 18 percentage points implies that approximately 36 million additional people were pushed into absolute poverty due to the crisis. After the peak point, the poverty rate started to decline again and reached the pre‐crisis level of approximately 15% at the end of 1999, implying that the lost time in poverty reduction due to the crisis was approximately 2.5years. However, the poverty rate after this point appears to have fluctuated. During 2001 and early 2002, poverty was on the rise again.
Trends in Total and Subgroup Income Inequality in the Singaporean Workforce
Authors: Mukhopadhaya Pundarik
Published: December 2003

This paper examines the trends in income inequality in Singapore using Labour Force Survey data from 1974 to 1998. Trends in inequality within and between age, educational and occupational groups are studied using the Theil inequality index. A new method based on the Gini coefficient is also utilized to explore the nature of inter‐temporal variation in within‐group inequality. Any increase within age‐group inequality is due to changing income shares, while the decrease in educational‐group inequality comes from decreases in within‐group inequality. The contribution of intereducation inequality has also increased over the years, as has inter‐occupational inequality.
Demarcation and the Scientistic Fallacy
Authors: Peterson Gregory R.
Published: December 2003

Abstract. For many theologians and philosophers, scientism is among the greatest of intellectual sins. In its most commonly cited form, scientism consists in claiming that science is the only source of real knowledge and, therefore, that what science does not discover does not exist. Because the charge of scientism is frequently levied, it is important to be clear about what exactly is being claimed in its name. I argue that scientism can best be understood as a fallacy, specifically as a kind of category mistake. Being clear about this requires an examination of the relationship of scientism to the question of demarcation between science and nonscience, a question that has potential implications for theology.
Is Nature Enough? No
Authors: Haught John F.
Published: December 2003

Abstract.This essay is based on a lecture delivered at the 2002 IRAS Star Island conference, the theme of which was “Is Nature Enough? The Thirst for Transcendence.” I had been asked to represent the position of those who would answer No to the question. I thought it would stimulate discussion if I presented my side of the debate in a somewhat provocative manner rather than use a more ponderous approach that would argue each point in a meticulous and protracted fashion. Here I lay out a theological position that finds naturalism wanting in three ways: in terms of human spiritual needs, in terms of the mind's need for deep explanation, and in terms of the perennial human search for truth. Again, the style of presentation, like that of the original lecture, prohibits the kind of philosophical development that an adequate answer to each of the issues requires. The purpose is that of evoking discussion on a most important question.