bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum ovalbumin‐specific immunoglobulin G responses during pregnancy reflect maternal intake of dietary egg and relate to the development of allergy in early infancy
Authors: Vance G. H. S. , Grimshaw K. E. C. , Briggs R. , Lewis S. A. , Mullee M. A. , Thornton C. A. , Warner J. O.
Published: December 2004

Background
The value of allergen elimination diets during pregnancy for primary prevention of infant allergy has been questioned. However, dietary compliance may influence effectiveness.

Objectives
To monitor egg intake during a randomized controlled trial of egg avoidance throughout pregnancy and lactation by serial measurements of serum ovalbumin (OVA) IgG concentration in conjunction with dietary diary record and also, to analyse specific IgG concentrations at birth in relation to infant allergic outcome.

Methods
Pregnant women, with personal or partner atopy, were randomized to complete dietary egg exclusion or an unmodified healthy diet before 20 weeks gestation. The infants were evaluated for atopy at 6 months of age. Serum food‐specific IgG concentrations were determined by ELISA in maternal samples collected at study recruitment and during labour, and in infant samples at birth (umbilical cord).

Results
Serum‐specific IgG to OVA, but not the unrelated allergen, cow's milk β‐lactoglobulin, decreased over pregnancy in egg‐avoiding women only (P<0.001). Cord OVA IgG concentration correlated with maternal IgG at delivery (r=0.944; P<0.001), and for infants born to atopic women, cord concentration was higher than that of their mother's (P<0.001). Infants with the lowest and highest cord IgG concentrations were the least likely, and those with mid‐range concentrations were the most likely, to be atopic by 6 months of age (P=0.008).

Conclusion
Serum OVA IgG concentration reflects egg consumption, thereby indicating dietary allergen doses to which the developing immune system might be exposed. Trans‐placental maternal IgG must be considered among early life factors that regulate infant atopic programming.
Expression of tyrosine hydroxylase and neuropeptide tyrosine in mouse sympathetic airway‐specific neurons under normal situation and allergic airway inflammation
Authors: Dinh Q. T. , Groneberg D. A. , Witt C. , Peiser C. , Cifuentes L. B. , Frossard N. , Klapp B. F. , Fischer A.
Published: December 2004

Background
The traditional neurotransmitter catecholamine and the neuropeptide tyrosine in sympathetic airway nerves have been proposed to be involved in the pathogenesis of airway diseases.

Objective
The aim of the present study was to investigate the effect of allergic airway inflammation on the expression of catecholamine enzyme tyrosine hydroxylase (TH), neuropeptide tyrosine (NPY) and tachykinins in mouse sympathetic airway ganglia.

Methods
Using neuronal tracing in combination with immunohistochemistry, the present study was designed to characterize TH, NPY and tachykinin profiles of superior cervical (SCG) and stellate ganglia after allergen challenge.

Results
The vast majority of fast blue‐labelled SCG neurons (allergen: 97.5±1.22% (mean±SEM) vs. controls: 94.5±1.48%, P=0.18) and stellate neurons (allergen: 95.3±1.01% vs. controls: 93.6±1.33%, P=0.34) were immunoreactive for TH. Of the TH immunoreactive and fast blue‐labelled SCG neurons, 52.0±1.01% allergen vs. 51.2±3.58% controls (P=0.83) and stellate neurons, 57.3%±0.97 allergen vs. 56.4±1.65% controls (P=0.64) were positive for TH only but not NPY, whereas 45.3±1.05% allergen vs. 43.3±1.18% controls (P=0.47) of fast blue‐labelled SCG neurons and 37.9±0.86% allergen vs. 37.1±1.24% controls (P=0.62) of fast blue‐labelled stellate neurons were immunoreactive for both TH and NPY immunoreactivities. There was a trend of an increase, but not significant one, in the percentage of TH‐/NPY‐immunoreactive and fast blue‐labelled neurons in allergen‐treated animals in comparison with the controls. Tachykinins, however, were not expressed by sympathetic neurons and were also not induced in sympathetic neurons after allergen challenge.

Conclusion
The present study indicates that allergic airway inflammation does not alter the expression of noradrenalin and NPY in sympathetic ganglia and also shows that sympathetic neurons do not respond to allergic airway inflammation with tachykinins induction. However, a participation of catecholamine and NPY in the pathogenesis of allergic airway inflammation cannot be excluded in the present study as a higher neurotransmitter output per neuron following allergen challenge could be possible.
Molecular and structural analysis of immunoglobulin E‐binding epitopes of Pen ch 13, an alkaline serine protease major allergen from Penicillium chrysogenum
Authors: Lai H.‐Y. , Tam M. F. , Chou H. , Lee S.‐S. , Tai H.‐Y. , Shen H.‐D.
Published: December 2004

Background
Through proteomic and genomic approaches we have previously identified and characterized an alkaline serine protease that is a major allergen (88% frequency of IgE binding) of Penicillium chrysogenum (Pen ch 13).

Objective
The aim of the present study is to identify the linear IgE‐binding epitopes of Pen ch 13.

Methods
IgE‐binding regions were identified by dot‐blot immunoassay using 11 phage‐displayed peptide fragments spanning the whole molecule of Pen ch 13. The minimal epitope requirements for IgE binding were further defined with overlapping peptides synthesized on derivatized cellulose membranes using SPOTs technology. The critical residues on the immunodominant epitopes were mapped through site‐directed mutagenesis. The locations of the IgE epitopes identified were correlated with a three‐dimensional structure of Pen ch 13.

Results
IgE antibodies in 35 serum samples reacted with at least one of the 11 peptide fragments of Pen ch 13. Peptide f‐2n (residues 31–61) showed a high‐intensity and the highest frequency (77%) of IgE binding. The frequencies of IgE binding to peptide f‐4 (residues 93–133), f‐1 (residues 1–37) and f‐7 (residues 168–206) were 51%, 34% and 31%, respectively. SPOTs assay narrowed down the region of IgE binding of f‐2n to residues 48–55 (GHADFGGR). Three, two and one epitope(s) that are four to nine amino acids in length, within f‐4, f‐1 and f‐7, respectively, were found. Site‐directed mutagenesis of Pen ch 13 revealed that substitution of His49 and/or Phe52 on Pen ch 13 with methionine resulted in proteins with drastic loss of IgE binding in seven sera tested. Proteins with amino acid replacements at residues 15–18 (RISS), or at residues 112 (I) and 116 (D) have lower IgE‐binding reactivity in one of the two patient's sera tested. Substituting residues 117 (W), 119 (V) and 120 (K) also block most of the IgE binding in one of the two patient's sera tested. In addition, replacing residues 203 (V) and 204 (D) along with a deletion at residue 206 (Y) diminished the IgE binding in two serum samples tested. A model was constructed based on the structure of P. cyclopium subtilisin protease that has >90% (256 out of 283 amino acids) sequence identity with Pen ch 13. The major epitope (GHADFGGR) on Pen ch 13 formed a loop‐like structure and was located at the surface of the allergen.

Conclusions
Several linear IgE‐reactive epitopes and their critical core amino acid residues were identified for the Pen ch 13 allergen. The major linear IgE‐binding epitope, 48GHADFGGR55, formed a loop‐like structure at the surface of the allergen. Substitution of His49 and/or Phe52 with methionine significantly reduced IgE‐binding to Pen ch 13. Mapping of these results on a 3D model of the allergen provides valuable information about the molecular basis of allergenicity for Pen ch 13 and for designing specific immunotherapeutics.
Biological effects of montelukast, a cysteinyl‐leukotriene receptor‐antagonist, on T lymphocytes
Authors: Spinozzi F. , Russano A. M. , Piattoni S. , Agea E. , Bistoni O. , De Benedictis D. , De Benedictis F. M.
Published: December 2004

Background
Montelukast (MNT), a cysteinyl‐leukotriene receptor (Cys‐LTR) antagonist, has anti‐inflammatory activity in the treatment of allergic diseases. If this effect is due only to blocking leukotrienes or also owing to inhibiting proliferation and survival of inflammatory cells, is actually unknown.

Objective
Testing the hypothesis that MNT could influence T lymphocyte functional behaviour in vitro.

Methods
Normal T lymphocytes were analysed for surface expression of Cys‐LTR1 and Cys‐LTR2 by means of monoclonal antibodies (mAbs), in the resting state and after activation with T helper type 2 cytokine or T cell receptor (TcR) stimulation. Proliferative activity, as well as IL‐4 andIFN‐γ production, were simultaneously determined in samples exposed to molar concentrations of MNT from 10−8 to 10−5. Programmed cell death in cultured samples was evaluated by means of propidium iodide and fluorescein isothiocyanate‐conjugated anti‐Annexin V mAb staining. The complementary DNA microarray technique was adopted to identify gene products involved in apoptosis induction.

Results
Resting T cells expressed low levels of Cys‐LTR. Upon anti‐CD3 mAb activation, a progressive increase in Cys‐LTR1 and ‐LTR2 expression was observed. Exposure to MNT reduced proliferative response to TcR engagement, increased IFN‐γ production and led to apoptosis at minimal concentrations of 10−6 m. A progressive loss in BAD and B cell lymphoma/leukaemia‐2 activities, and an increase in the expression of CD27, TRAF3, TRAIL, p53 and Fas genes were also observed.

Conclusions
Biological effects of MNT delineate a complex picture of gene activation and repression, probably induced by Cys‐LTR blockade. The induction of apoptosis in allergen‐specific T cell population, as a final result, appears fundamental in the treatment of asthma.
The effect of specific immunotherapy on the expression of costimulatory molecules in late phase reaction of the skin in allergic patients
Authors: Plewako H. , Arvidsson M. , Oancea I. , Hasséus B. , Dahlgren U. , Rak S.
Published: December 2004

Background
Specific immunotherapy (SIT) modulates immune responses to allergens resulting in improvement of allergic symptoms. However, the mechanisms behind the clinical changes are not clear. Participation of costimulatory molecules on antigen‐presenting cells and T cells in the process of antigen recognition is suggested to be of essential importance. The SIT effect on expression of costimulatory molecules has not been earlier examined.

Methods
Forty‐one birch‐allergic patients were treated with SIT or placebo. After 1 year of treatment skin biopsies were obtained 24 h following allergen challenge. Sections were stained with antibodies against: EG2 (eosinophils), CD4 (T cells), CD68 (macrophages), CD1a (Langerhans cells), CD28 (on T cells) and costimulatory molecules (CD80, CD86).

Results
Following allergen challenge number of the CD4+ and CD68+ cells increased significantly (P=0.002, 0.0001, respectively) in the placebo, but not in the SIT‐treated patients. The difference between groups was significant (P=0.003, 0.01, respectively). The numbers of EG2+ cells increased significantly in both groups. CD80+ cell numbers increased in the placebo (P=0.01) but not in the SIT group. The number of CD86+ cells increased in both groups (placebo, P=0.001; SIT, P=0.01) but significantly less in the SIT group (P=0.05). The numbers of CD28+ cells increased in the placebo (P=0.001) but remained unchanged in the SIT group. The difference between the groups was significant (P=0.05).

Conclusion
There were lower numbers of cells expressing costimulatory molecules in SIT‐treated than in placebo‐treated patients. Decreased costimulation may lead to diminished immune response following allergen exposure. This could be an important factor contributing to the clinical improvement after SIT.
Reticular basement membrane thickening in airways of lung transplant recipients is not affected by inhaled corticosteroids
Authors: Ward C. , De Soyza A. , Fisher A. J. , Pritchard G. , Forrest I. A. , Corris P. A.
Published: December 2004

Introduction
Chronic rejection is a major problem for all lung transplant programmes, which is functionally manifested by fixed airflow limitation, Bronchiolitis Obliterans Syndrome (BOS). The inclusion of a Pre‐BOS category, BOS0∼p, in newly revised guidelines, recognizes the potential importance of early changes. We have previously demonstrated reticular basement membrane (Rbm) thickening in clinically stable lung transplant recipients free from BOS. The present study extends this, testing the hypothesis that inhaled corticosteroid (ICS) therapy will lead to a decrease in Rbm thickness in lung transplant recipients.

Methods
A parallel group, bronchoscopic intervention study of clinically stable lung allograft recipients, free from BOS, but with evidence of airway inflammation. Following baseline assessment of Rbm thickening, subjects were randomized to 3 months of either chlorofluorocarbon‐driven beclomethasone diproprionate (BDP) 400 μg b.i.d., or a formulation designed to yield at least an equivalent dose, hydrofluoroalkane‐driven BDP, 200 μg b.i.d.

Results
Three months treatment with a moderate dose of ICS, including a formulation designed for preferential small airway deposition, had no effect on Rbm thickening (13±3 vs. 14±5 μm post‐ICS).

Conclusion
Our data would suggest that airway remodelling can occur early in lung allografts and is not affected by moderate dose ICS therapy. Longitudinal studies are required to describe the pathophysiological processes involved in BOS, and specifically to elucidate potential relationships between airway remodelling, airflow obstruction and allograft failure.
Identification of anti‐inflammatory drugs according to their capacity to suppress type‐1 and type‐2 T cell profiles
Authors: Moed H. , Stoof T. J. , Boorsma D. M. , Von Blomberg B. M. E. , Gibbs S. , Bruynzeel D. P. , Scheper R. J. , Rustemeyer T.
Published: December 2004

Background
Down‐regulation or modulation of T cell activity by immunosuppressive drugs is an effective treatment in diseases where exaggerated T cell responses play a role. A primary effect of the anti‐inflammatory drugs (AIDs) is inhibition of the synthesis of growth factors, such as IL‐2, thereby down‐regulating T cell proliferation. However, it is still largely unknown to what extent these AIDs are able to down‐regulate specifically type‐1 or type‐2 T cell cytokine production, and whether they can down‐modulate chemokine receptor expression, thereby preventing migration of T cells to the site of inflammation.

Objective
We investigated the suppressive effect of dermatologically used AID (cyclosporin A (CsA), lactoferrin (LF), 1α, 25‐dihydroxyvitamin D3 (VD3), hydrocortisone (HC), di‐methyl‐fumarate (DMF), diclofenac (DF)) on both type‐1 and type‐2 T cells. Since allergic contact dermatitis is a skin disorder in which an exaggerated T cell response of both types of T cell subsets can be observed, we used this disorder as a model to study the capacity of AID to suppress type‐1 or type‐2 T cell responses.

Methods
Peripheral blood mononuclear cells of nickel allergic patients were cultured in the presence of allergen and increasing concentrations of AID. Proliferation was determined by measuring 3H thymidine incorporation; chemokine receptor (CCR10, CCR4, CXCR3) expression was studied by flow cytometric analysis and IFN‐γ or IL‐5 cytokine production was measured by ELISA.

Results
Three major patterns can be distinguished regarding the effect of AID on T cell responses. The first group, including CsA and LF, inhibited non‐selectively T cell proliferation, chemokine receptor expression and cytokine production, with CsA as the most potent drug tested. A second group of AID, which included VD3, HC and DMF, suppressed mainly type‐1 T cell responses, as revealed by strong interference with IFN‐γ production and CXCR3 expression, and limited effects on either or both IL‐5 and CCR4 expression. The third pattern was displayed by DF, which down‐regulated IL‐5 production and CCR4 expression, whereas IFN‐γ and CXCR3 were unaltered.

Conclusions
Using a contact allergy model, we have demonstrated that various AIDs show distinct pharmacological profiles in that either type‐1 or type‐2 or both T cell responses are suppressed. These results should contribute to a more rational selection of AID in treating inflammatory skin diseases mediated by either or both of these T cell subsets.
Determination of the T cell epitopes of the lipocalin allergen, Rat n 1
Authors: Jeal H. , Draper A. , Harris J. , Taylor A. Newman , Cullinan P. , Jones M.
Published: December 2004

Background
Laboratory animal allergy (LAA) is an important cause of occupational sensitization and asthma. Rats are a frequent cause of LAA and the major rat allergen, Rat n 1, is a member of the lipocalin protein family, which includes several other animal allergens such as the cow allergen, Bos d 2. To date, Bos d 2 is the only mammalian lipocalin allergen to have been studied in detail.

Objective
We undertook a cross‐sectional study of a large population of individuals exposed to laboratory rats to determine the proliferative responses of peripheral blood mononuclear cells (PBMCs) to the major rat allergen, Rat n 1.

Methods
Eighty‐three cases (defined by a positive skin prick test (SPT) 3 mm and/or a positive RAST 2% binding) and 274 referents without specific IgE to rats were tested for their proliferative responses of PBMCs to rat allergen. Cytokine release to rat urinary protein was examined in 28 sensitized and 42 non‐sensitized exposed individuals.

Results
Proliferation to rat urinary protein was weak in all individuals. Four regions within Rat n 1 were identified as containing potential immunodominant T cell epitopes and three of these co‐localized within the conserved regions of the lipocalin molecule. All four regions within Rat n 1 overlapped considerably with the characterized epitopes of the lipocalin allergen, Bos d 2. IL‐5 and ratios of IL‐5/IFN‐γ were significantly increased in cases.

Conclusion
The response to Rat n 1 is remarkably similar to the cow lipocalin allergen Bos d 2. T cell epitopes within lipocalins appear to co‐localize with the conserved regions of the molecule. LAA is characterized by an increased production of IL‐5. Investigation of other lipocalin allergens will provide further information about the allergenicity of this group of proteins.
Latex allergy in infants younger than 1 year
Authors: Kimata H.
Published: December 2004

Background
The prevalence of latex allergy in children is increasing worldwide. Previous multiple operations or atopic predisposition are known risk factors. In contrast, only sporadic cases of latex allergy have been reported in infants younger than 1 year, and the causative latex‐containing products or symptoms in young infants have not been studied in detail.

Objective
The purpose of this study is to analyse the symptoms and risk factors of latex allergy in young infants.

Methods
Cases of latex allergy in infants younger than 1 year were studied in detail. Clinical course, causative latex‐containing products were spotted and detailed analysis for latex allergy in patients and patients' parents was performed.

Conclusion
We report nine cases of latex allergy in infants younger than 1 year. None of them have any abnormality or previous operations. Six patients had atopic eczema/dermatitis syndrome, one patient had bronchial asthma, whereas two patients had no overt allergic diseases. Symptoms of latex allergy were wheezing, swelling of face or lips, facial rash, or anaphylaxis, and causative latex‐containing products were teat, pacifier, nose cleaner, teether, balloon, or enema tube. All of the nine patients had positive skin prick test to latex and extract from causative latex‐containing products, whereas eight patients had positive serum latex‐specific IgE. Study for family history revealed that latex allergy was noted in either father or mother in six patients, in both father and mother in one patient, whereas no latex allergy was noted in parents in two patients. It should be noted that all of these patients had latex‐induced symptoms at home. Latex allergy in young infants may not be unusual. Physicians should be aware of latex allergy, and care should be taken to avoid contact with latex in young infants, especially when there is family history for latex allergy.
Heparin‐induced recurrent anaphylaxis
Authors: Berkun Y. , Haviv Y. S. , Schwartz L. B. , Shalit M.
Published: December 2004

Background
Heparin‐related immediate‐type hypersensitivity reactions like urticaria, angio‐oedema or bronchospasm are very rare, and only a few cases of anaphylaxis‐like responses because of heparin have been described. However, the mechanisms underlying these reactions and the role of mast cells in their pathogenesis have not been elucidated.

Objectives
We report a patient with end‐stage renal disease who presented with recurrent anaphylaxis after receiving heparin during haemodialysis. The underlying aetiology was obscured by the initiation of haemodialysis with its known anaphylactic‐like side‐effects. The diagnosis of hypersensitivity to heparin was confirmed by the clinical picture, positive skin tests and elevated serum tryptase levels.

Materials and methods
We performed prick and intradermal skin tests with heparin, enoxaparin and danaparoid heparinoid. Total and mature tryptase levels were measured in serum by ELISAs at 1, 24 and 36 h following the reaction.

Results
An elevated mature tryptase level was found at 1 h, which returned to normal levels at 24 and 36 h. A high total tryptase level was detected at 1 h, but remained somewhat elevated at 24 h. Prick tests were negative with the three compounds. Intradermal skin tests with heparin and enoxaparin were both positive, while with danaparoid negative. Following negative skin test results, danaparoid was used as an anticoagulant during dialysis for the next 3 years without any adverse effects.

Conclusions
In conclusion, we report the first case of heparin‐induced anaphylaxis confirmed by an elevated level of mature tryptase in serum. Following skin tests, the patient was treated with danaparoid during haemodialysis sessions three times a week without any adverse effects. Because of increasing use of heparin in daily medical practice, physicians should be aware of possible immediate hypersensitivity reactions to this medication and know how to diagnose and treat them.
Differential capacity of CD8α+ or CD8α− dendritic cell subsets to prime for eosinophilic airway inflammation in the T‐helper type 2‐prone milieu of the lung
Authors: Hammad H. , De Vries V. C. , Maldonado‐Lopez R. , Moser M. , Maliszewski C. , Hoogsteden H. C. , Lambrecht B. N.
Published: December 2004

Background
Different subsets of dendritic cells (DCs), identified in mouse spleen by their differential expression of CD8α, can induce different T‐helper (Th) responses after systemic administration. CD8α− DCs have been shown to preferentially induce Th type 2 (Th2) responses whereas CD8α+ DCs induce Th1 responses.

Objective
To study if these DC subsets can still induce different Th responses in the Th2‐prone milieu of the lung and differentially prime for eosinophilic airway inflammation, typical of asthma.

Methods
Donor mice first received daily Flt3L injections to expand DC numbers. Purified CD8α+ or CD8α− splenic DCs were pulsed with ovalbumin (OVA) or phosphate‐buffered saline and injected intratracheally into recipient mice in which carboxyfluorescein diacetate succinimidyl ester‐labelled OVA‐specific T cell receptor transgenic T cells had been injected intravenously 2 days earlier. T cell proliferation and cytokine production of Ag‐specific T cells were evaluated in the mediastinal lymph nodes (MLNs) 4 days later. The capacity of both subsets of DCs, to prime for eosinophilic airway inflammation was determined by challenging the mice with OVA aerosol 10 days later.

Results
CD8α− DCs migrated to the MLN and induced a vigorous proliferative T cell response accompanied by high‐level production of IL‐4, IL‐5, IL‐10 and also IFN‐γ during the primary response and during challenge with aerosol, leading to eosinophilic airway inflammation. In the absence of migration to the MLN, CD8α+ DCs still induced a proliferative response with identical levels of IFN‐γ but reduced Th2 cytokines compared with CD8α− DCs, which led to weak eosinophilic airway inflammation upon OVA aerosol challenge. Unpulsed DCs did not induce proliferation or cytokine production in Ag‐specific T cells.

Conclusion
CD8α− DCs are superior compared with CD8α+ DCs in inducing Th2 responses and eosinophilic airway inflammation in the Th2‐prone environment of the lung.
Predictive power of cytomorphological features in equivocal (C3, C4) breast FNAC
Authors: Moyes C. , Dunne B.
Published: December 2004

Definitive immediate diagnosis in breast fine needle aspiration cytology (FNAC) remains the aim for cytopathologists. We reviewed 72 consecutive equivocal (C3 and C4) aspirates with respect to 16 cytomorphological criteria. We assessed the power of each criterion at predicting either a malignant [positive predictive value (PPV)] or a benign [negative predictive value (NPV)] diagnosis by correlation with follow‐up histology. Blind review led to 34% of cases being correctly definitively diagnosed. Eccentrically placed epithelial cell nuclei (PPV = 88%, sensitivity = 67%, specificity = 87%) and coarse nuclear chromatin (PPV = 81%, sensitivity = 72%, specificity = 83%) are the features that are most useful in predicting malignancy in this selected series. The presence of myoepithelial cells within epithelial groups is not a good indicator of a benign diagnosis (NPV = 24%, sensitivity = 80%, specificity = 53%).
The role of nipple discharge cytology in the diagnosis of breast disease: a study of 1948 nipple discharge smears from 1530 patients
Authors: Gupta R. K. , Gaskell D. , Dowle C. S. , Simpson J. S. , King B. R. , Naran S. , Lallu S. , Fauck R.
Published: December 2004

In this study a review of 1948 nipple discharge (ND) samples from 1530 patients in the age range of 18–83 years was undertaken to determine whether cytological findings from ND smears could provide useful diagnostic information regarding various breast lesions. The study included 1494 females and 36 males and was carried out during a period of 20 years 8 months. The clinical information in all patients was obtained from clinicians (coauthors†), medical records and a review of biopsies in 205 patients who had undergone surgery following the cytodiagnosis. Of the ND samples examined, 1480 were unilateral while 468 were from 234 bilateral ND. The cytodiagnoses were: benign 624, inadequate (despite two to three repeat samples) 492, inflammatory 96, papillary lesion not otherwise specified (NOS) 229, suspicious 22 (21 females, one male) and malignant 67 (63 females, four males). A breast biopsy in the 22 suspicious cases revealed breast carcinoma in 18 cases (females n = 17, male n = 1), atypical ductal hyperplasia (female n = 1), fibroadenoma (female n = 1) and a papilloma in two females. In the 67 cases with a diagnosis of malignancy 65 revealed a breast carcinoma in the biopsy (female n = 62, male n = 3) while one female was diagnosed as fibroadenoma and one male as florid gynaecomastia. In 63 cases (females n = 61; males n = 2) with clinical lumpy areas consistent with the diagnosis of fibrocystic condition in ND, the biopsy confirmed a fibrocystic process. In 53 of 229 cases with ND findings suggestive of a papillary lesion (NOS) the biopsy revealed a papilloma in 41 cases while in 12 cases no lesion was found. In the remaining cases of all the groups only a clinical follow‐up and appropriate investigations were performed with no untoward outcome. Based on our study it is felt that cytological examination of ND smears seems to be a reasonably specific method in the diagnosis of malignant and suspicious cases but may be somewhat less specific for other diagnoses.
Analysis of forces developed during mechanical preparation of extracted teeth using RaCe rotary instruments and ProFiles
Authors: Da Silva F. M. , Kobayashi C. , Suda H.
Published: December 2004

Aim  To compare the torque and load during instrumentation with ProFile and RaCe nickel‐titanium rotary instruments.

Methodology  Thirty human incisor roots 12 mm in length were embedded in epoxy resin, and divided into three groups of 10 specimens each. Instruments employed in each group were as follows: RaCe .02 Step Back Files in group 1; RaCe .04 Step Back Files in group 2; and .04 ProFiles in group 3. Two load cells, whose outputs were connected to a digital oscilloscope, recorded torque and vertical load. Data were analysed by one‐way anova.

Results  Torque values were statistically different between groups 1 and 3, and between groups 2 and 3 (torque was higher in group 3 than in groups 1 and 2). Vertical loads were statistically higher in group 3 than in groups 1 and 2.

Conclusions  Torsional and vertical forces can be evaluated during instrumentation of straight root canals using the device and methods described in this study. When the step‐back technique was employed, torque and vertical load obtained with RaCe instruments were lower than that obtained with ProFiles.
A comparison between two electronic apex locators: an in vivo investigation
Authors: Venturi M. , Breschi L.
Published: December 2004

Aim  To compare in vivo the Apex Finder and Root ZX electronic apex locators (EALs) at five different stages during root canal instrumentation.

Methodology  The Apex Finder and Root ZX were used in 64 teeth with either vital or necrotic pulps. Informed consent was obtained by each patient under a study protocol approved by an ethical committee from the University of Trieste. Measurements were made: (stage 1) before instrumentation and irrigation; (stage 2) after brief filing, irrigation with 70% isopropyl alcohol and partial drying; (stage 3) after canal lubrication with EDTA gel (RC‐Prep); (stage 4) after complete instrumentation and irrigation with NaOCl 5%; (stage 5) after drying of the final instrumented canal. Stages 2, 3 and 5 were considered low canal conductivity conditions and stage 4 as high. Teeth were then extracted and a size 15 K‐file was inserted until its tip was observed under stereomicroscope to reach the foramen and the corresponding length was recorded to an accuracy of 0.25 mm and compared with values derived from the EALs.

Results  The data revealed 133 unstable measurements (out of 640): some (68) related to low canal conductivity conditions (more frequently for Root ZX, 67; P < 0.05), and others (63) related to NaOCl presence in the canal (more frequently for Apex Finder, 58; P < 0.05). Accuracy was calculated only on stable measurements. The Root ZX showed significantly (P < 0.05) more precise measurements overall (−0.03 ± 0.39 mm) compared with the Apex Finder (−0.31 ± 0.46 mm). Under dry canal conditions the Apex Finder provided the greatest accuracy (−0.0 ± 0.21) compared with the Root ZX (−0.05 ± 0.32) (significance P < 0.05).

Conclusions  Under the five different clinical situations both EALs revealed accurate measurements. Apex Finder was negatively influenced by NaOCl in the root canal. The Root ZX was more frequently unable to reveal stable measurements in low conductivity canals.
The adoption of new endodontic technology amongst Danish general dental practitioners
Authors: Bjørndal L. , Reit C.
Published: December 2004

Aim  To assess the adoption of new endodontic technology in a population of Danish practitioners.

Methodology  Members of the Copenhagen Dental Association (n = 1156) were approached with a questionnaire concerning the frequency of various endodontic procedures. Three options were available: often, occasionally and never. Responses were anonymous. The statistical analyses were performed as studies of association in two‐ or three‐way contingency tables, and with Goodman–Kruskal's γ‐coefficient as the basic tool chosen.

Results  Only data from general practitioners (GPs) in private practice were analysed (n = 956). The response rate was 72%. NiTi hand instruments were often used to negotiate canals by 18%, whilst 10% often used NiTi rotary systems. Electronic apex locators were often employed by 15%. Nineteen per cent reported that warm gutta‐percha was often used. A majority (53%) often spend two sessions to instrument a molar, and 20% often needed three or more sessions to finish the shaping phase. To complete a treatment of a nonvital case most practitioners reported to use at least three appointments. Only 4% frequently applied rubber dam.

Conclusions  The adoption of new endodontic technology is at an early stage amongst Danish GPs. A new revised remuneration system might influence the rate of adoption, allowing the practitioners to act more rationally and produce a higher frequency of good‐quality root fillings. Progress towards high quality endodontics might be hindered by the nonuse of rubber dam.
O‐Linked glycosylation and functional incompatibility of porcine von Willebrand factor for human platelet GPIb receptors
Authors: Schulte am Esch Jan , Robson Simon C. , Knoefel Wolfram T. , Hosch Stefan B. , Rogiers Xavier
Published: December 2004

Abstract:  Background:  Xenograft rejection is associated with vascular inflammation, thrombocytopenia and the accelerated consumption of coagulation factors. Primary biological incompatibilities of the xenograft in the regulation of clotting appear to amplify pathological processes associated with rejection. The functional incompatibility of porcine von Willebrand factor (vWF) expressed within the xenograft vasculature may heighten interactions with the primate platelet receptor GPIb, hence augmenting formation of platelet microthrombi and vascular injury. Here, we address the functional impact of O‐linked glycosylation of the vWF A1 domain on primate platelet activation.

Methods:  Recombinant human or porcine vWF A1‐domains were transiently over‐expressed in COS‐7 cells as FLAG‐tagged fusion protein, linked to plasma membranes via GPI anchors. O‐linked glycosylation was blocked by the addition of phenyl‐α‐GalNAc2 to cultures. Expressed vWF‐A1 domains were characterized utilizing cytofluometric‐ and Western blot analyses.

Results:  Cytofluometric analysis confirmed equivalent levels of human and porcine vWF A1‐domain expression irrespective of the levels of O‐linked glycosylation. Differential glycosylation patterns of vWF‐A1 under these conditions were confirmed by Western blot analyses. Native porcine vWF A1‐domains had enhanced human platelet activation potential when compared with human recombinant vWF A1. However, the loss of O‐linked glycosylation abolished differences in aggregatory responses between human and porcine vWF A1 domains.

Conclusions:  Various degrees of O‐linked glycosylation of vWF‐A1‐domains modulate levels of functional interaction with platelet receptor GPIb and consequent platelet aggregation responses in vitro. These data may have implications for outcomes of xenotransplantation. We speculate that alterations in glycosylation of vWF and other adhesion proteins associated with the targeting of the α1,3‐Gal‐epitope in mutant swine may have salutatory effects on the primate platelet activation observed in these xenografts.
Evidence of macrophage receptors capable of direct recognition of xenogeneic epitopes without opsonization
Authors: Rees Michael A. , Butler Andrew J. , Brons I. Gabrielle M. , Negus Margaret C. , Skepper Jeremy N. , Friend Peter J.
Published: December 2004

Abstract:  Background:  We have previously demonstrated that porcine livers perfused with human blood remove most of the erythrocytes from three units of human blood over the course of a 72‐h extracorporeal perfusion. Red blood cell loss did not appear to involve classical complement pathway‐mediated hemolysis, but instead resulted from porcine Kupffer cell phagocytosis.

Methods:  We developed a method incorporating collagenase digestion and metrizamide separation to isolate and maintain porcine Kupffer cells in primary culture. An in vitro rosetting assay was used to assess the binding of human and porcine erythrocytes to porcine Kupffer cells. Immunohistochemistry was used to confirm the presence of porcine macrophages. The rosetting assay was quantified using 51Cr‐labeling of erythrocytes to assay for both rosette formation and phagocytosis.

Results:  Porcine Kupffer cells were successfully isolated and maintained in primary culture. The presence of porcine macrophages was confirmed using the monoclonal antibody 74‐22‐15A. Human, but not porcine, erythrocytes were bound in an in vitro rosetting assay as confirmed by immunohistochemistry, electron microscopy and 51Cr‐quantitation. Porcine Kupffer cells bound human erythrocytes regardless of the presence of opsonizing antibody. Approximately 70% of the isolated porcine Kupffer cells demonstrated the capacity to bind non‐opsonized human erythrocytes. Phagocytosis was not observed.

Conclusions:  Using primary porcine Kupffer cell cultures, we have demonstrated that a subpopulation of porcine macrophages has the ability to recognize specifically xenogeneic human erythrocyte epitopes without the need for prior opsonization. The possibility is discussed that lectin‐mediated carbohydrate binding plays a role in the cellular and humoral recognition and rejection of xenografts.
Abdominal manifestations of cystic fibrosis in adults: A review
Authors: Constantine S , Au VWK , Slavotinek JP
Published: December 2004

Gastrointestinal manifestations of disease are present in most adults with cystic fibrosis. Radiologists are familiar with the classical imaging characteristics of end‐stage pulmonary disease and the radiological findings of meconium ileus in neonates. As most patients now live into adulthood, recognition of the imaging appearances of abdominal disease is important to enable prompt diagnosis and treatment. Accordingly, this article presents typical imaging appearances of the adult gastrointestinal manifestations of cystic fibrosis.
Australian and New Zealand three‐dimensional conformal radiation therapy consensus guidelines for prostate cancer
Authors: Skala M , Berry M , Duchesne G , Gogna K , Tai K‐H , Turner S , Kneebone A , Rolfo A , Haworth A
Published: December 2004

Three‐dimensional conformal radiation therapy (3DCRT) has been shown to reduce normal tissue toxicity and allow dose escalation in the curative treatment of prostate cancer. The Faculty of Radiation Oncology Genito‐Urinary Group initiated a consensus process to generate evidence‐based guidelines for the safe and effective implementation of 3DCRT. All radiation oncology departments in Australia and New Zealand were invited to complete a survey of their prostate practice and to send representatives to a consensus workshop. After a review of the evidence, key issues were identified and debated. If agreement was not reached, working parties were formed to make recommendations. Draft guidelines were circulated to workshop participants for approval prior to publication. Where possible, evidence‐based recommendations have been made with regard to patient selection, risk stratification, simulation, planning, treatment delivery and toxicity reporting. This is the first time a group of radiation therapists, physicists and oncologists representing professional radiotherapy practice across Australia and New Zealand have worked together to develop best‐practice guidelines. These guidelines should serve as a baseline for prospective clinical trials, outcome research and quality assurance.
Three‐dimensional conformal radiotherapy in the treatment of prostate cancer in Australia and New Zealand: Report on a survey of radiotherapy centres and the proceedings of a consensus workshop
Authors: Tai K‐H , Duchesne G , Turner S , Kneebone A , See A , Gogna K , Berry M
Published: December 2004

There is an increasing use of 3‐D conformal radiotherapy (3DCRT) in the radiotherapeutic management of prostate cancer. The Faculty of Radiation Oncology Genito‐Urinary Group carried out a survey of Australian and New Zealand radiotherapy centres in the preparation of a consensus workshop. Of the 19 centres that were represented, there were 24 radiation oncologists, 16 radiation therapists and 12 medical physicists. The survey collected demographic information and data on the practices undertaken at those centres when delivering curative radiotherapy in the treatment of prostate cancer. There was much variation in the delivery of treatment in the areas of patient set‐up, contouring of target volumes and organs of interest during computer planning, the techniques and the dose constraints used in these techniques, the use of adjuvant androgen deprivation therapy and the quality assurance processes used in monitoring effects of treatment. This variability reflects the range of data in the published literature. Emerging trends of practices were also identified. This is a first report on a multi‐disciplinary approach to the development of guidelines in 3DCRT of prostate cancer.
Computed tomography and complicated peptic ulcer disease
Authors: Pun E , Firkin A
Published: December 2004

Peptic ulcer disease (PUD) can present with many complications including inflammation, ulceration and perforation. Improvements in CT have enabled better imaging of the gastroduodenal area. Three cases of complicated PUD detected on CT are presented with a brief review of the current literature.
The Civil Intifada:1 The Power and Politics of the Palestinian Census
Authors: Wilkins Karin Gwinn
Published: December 2004

The Palestinian census of December 1997 holds both symbolic power, grounding a national identity within an intended modern, sovereign structure, and instrumental value, serving as a basis for social and economic development. Some scholars privilege the role of domination in this enumeration process, imposing official categorizations on people for the purpose of state control. However, in this article I argue that the census also has the potential to promote resistance, contingent upon the nature of the agency implementing the process and the historical circumstances of the community engaged in this exercise. In this case, Palestinian and Israeli governments compete over the parameters of this research implementation, particularly within the confines of Jerusalem, recognized by each as its (intended and existing) capital. Based on personal interviews, official documents and secondary sources, I describe this process in relation to other attempts to articulate a Palestinian community, and characterize the census within the context of a Palestinian political struggle for sovereignty against a dominant Israeli state.
Planned Resettlement, Unexpected Migrations and Cultural Trauma in Laos
Authors: Evrard Olivier , Goudineau Yves
Published: December 2004

Though not officially considered a ‘policy’ by the Lao government, resettlement of ethnic minorities has become a central feature of the rural development strategy in Laos. Over the past ten years, a majority of highland villages have been resettled downhill, and the local administrations are planning to move the remaining villages in the coming years. This article draws on a national survey about resettlement in Laos, commissioned by UNESCO and financed by UNDP, that was undertaken by the authors. It focuses on the consequences of these huge shifts of population and on the social and cultural dynamics that underlie them. It shows that the planned resettlements, which are intended to promote the ‘settling’ of the highland populations by enforcing the ban on slash‐and‐burn agriculture and opium growing, actually cause increased and diversified rural mobility. This in turn complicates the implementation of the rural development policy and the political management of interethnic relationships. In other words, the ‘settling’ process promoted by the State, because of its broad and often tragic social consequences, can paradoxically generate unplanned or unexpected further migrations, which could be called ‘resettlement‐induced forms of mobility’
Degrees without Freedom: The Impact of Formal Education on Dalit Young Men in North India
Authors: Jeffrey Craig , Jeffery Roger , Jeffery Patricia
Published: December 2004

This article considers the capacity of formal education to undermine established processes of caste and class reproduction in an area of north India, with particular reference to the views and strategies of educated Dalit young men. It draws on quantitative and qualitative research conducted by the authors in a village in Bijnor district, western Uttar Pradesh (UP). We discuss how educated Dalit young men perceive education, how they seek to use educational credentials to obtain ‘respectable’ jobs, and how they react when this strategy fails. Increased formal education has given Dalit young men a sense of dignity and confidence at the village level. However, these men are increasingly unable to convert this ‘cultural capital’ into secure employment. This has created a reproductive crisis which is manifest in an emerging culture of masculine Dalit resentment. In response to this culture, Dalit parents are beginning to withdraw from investing money in young mens’ higher secondary and tertiary‐level education. Without a substantial redistribution in material assets within society, development initiatives focused on formal education are likely to be only partially successful in raising the social standing and economic position of subordinate groups.
TO WHAT EXTENT HAS FISHER'S RESEARCH PROGRAM BEEN FULFILLED IN AUSTRALIA?
Authors: Mayo Oliver
Published: December 2004

This paper reviews Fisher's research program, showing how it constituted a theoretical basis for Darwin's evolutionary, genetical and experimental work, and identifies those fields where Fisher, through his influence on colleagues and students, caused some of his aims to be carried through in Australia, particularly in experimental design and evolutionary genetics.
ESTIMATING THE FALSE NEGATIVE FRACTION FOR A MULTIPLE SCREENING TEST FOR BOWEL CANCER WHEN NEGATIVES ARE NOT VERIFIED
Authors: Lloyd Chris J. , Frommer Donald
Published: December 2004

This paper aims to estimate the false negative fraction of a multiple screening test for bowel cancer, where those who give negative results for six consecutive tests do not have their true disease status verified. A subset of these same individuals is given a further screening test, for the sole purpose of evaluating the accuracy of the primary test. This paper proposes a beta heterogeneity model for the probability of a diseased individual ‘testing positive’ on any single test, and it examines the consequences of this model for inference on the false negative fraction. The method can be generalized to the case where selection for further testing is informative, though this did not appear to be the case for the bowel‐cancer data.
BAYESIAN DETECTION AND ANALYSIS OF CHANGING TRANSITION MATRICES OF STATIONARY MARKOV CHAINS
Authors: Groenewald P.C.N. , Schoeman A.C.
Published: December 2004

This paper considers the detection of abrupt changes in the transition matrix of a Markov chain from a Bayesian viewpoint. It derives Bayes factors and posterior probabilities for unknown numbers of change‐points, as well as the positions of the change‐points, assuming non‐informative but proper priors on the parameters and fixed upper bound. The Markov chain Monte Carlo approach proposed by Chib in 1998 for estimating multiple change‐points models is adapted for the Markov chain model. It is especially useful when there are many possible change‐points. The method can be applied in a wide variety of disciplines and is particularly relevant in the social and behavioural sciences, for analysing the effects of events on the attitudes of people.
ROBUST NON‐PARAMETRIC ESTIMATION OF GENOTYPE–PHENOTYPE RELATIONSHIPS IN HUMAN PEDIGREES
Authors: Huggins Richard M. , Loesch Danuta Z.
Published: December 2004

Non‐parametric estimation of functional relationships is an important part of data analysis, particularly in the exploratory stages. This paper considers non‐parametric estimation of the mean functions in family studies using weighted robust estimating equations while retaining a fully parametric model for the covariance structure. The proposed procedure allows an exploratory examination of complex pedigree data that is an invaluable aid in determining appropriate models. This is illustrated by an examination of the relationship between IQ and the level of a particular protein in individuals collected as part of a large family study.