bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural cell adhesion molecule expression in plasma cells in bone marrow biopsies and aspirates allows discrimination between multiple myeloma, monoclonal gammopathy of uncertain significance and polyclonal plasmacytosis
Authors: Martín P , Santón A , Bellas C
Published: December 2004

Aims:  Differential diagnosis between multiple myeloma (MM), monoclonal gammopathy of uncertain significance (MGUS), and polyclonal plasmacytosis may be difficult in cases with not much bone marrow infiltration. Normal plasma cells express the antigens CD138, CD38, CD19, CD10 and D‐related human leucocyte antigen (HLA‐DR). Myelomatous plasma cells lack B lymphoid‐associated markers and may express cell surface antigens associated with other haematopoietic lineages such as NCAM/CD56 (neural cell adhesion molecule). Recently, a monoclonal antibody, anti‐CD56, has become available that can be used in fixed tissues embedded in paraffin, and it has been reported that osteoblastic cells of trabecular bone strongly express NCAM/CD56.

Methods and results:  We analysed NCAM molecule expression in 35 samples from patients with plasma cell disorders: 14 cases of MM, 16 cases of MGUS, and five cases of polyclonal plasmacytosis using immunohistochemistry in parallel in bone marrow core biopsies processed routinely and in bone marrow smears from the same patients. Of the MM samples 78% were CD56+ in smears and 92% positive in biopsies. We did not find strong CD56 expression in MGUS samples. One of five samples of polyclonal plasmacytosis was CD56+. A case was considered to be positive for CD56 expression if >50% of the CD138+ plasma cells expressed NCAM with an intensity on a par with that of the osteoblasts.

Conclusion:  We conclude that CD56 antibody is a very useful marker in the study of plasma cell proliferation in bone marrow biopsies and in bone marrow aspirates and is a great help in discriminating between MM, MGUS, and polyclonal plasmacytosis, especially in those cases with low infiltration.
Preferential HER‐2/neu overexpression and/or amplification in aggressive histological subtypes of invasive breast cancer
Authors: Varga Z , Zhao J , Öhlschlegel C , Odermatt B , Heitz P U
Published: December 2004

Aims:  To investigate whether alterations of the HER2 gene occur more frequently in histologically unfavourable subtypes of invasive breast cancer.

Methods:  The study was composed of nine invasive apocrine, six lipid‐rich, 12 glycogen‐rich, 11 micropapillary and 33 pleomorphic lobular breast carcinomas. Lymph node involvement was represented in all subgroups. HER2 status was confirmed in all cases by using immunohistochemistry (CB11, Herceptest) and fluorescent in‐situ hybridization (FISH) analysis (Vysis).

Results:  Micropapillary and apocrine carcinomas showed the highest rate of protein overexpression (72% and 66%) and gene amplification (45% and 44%). Protein overexpression was common in poorly differentiated pleomorphic lobular carcinomas (56%); however, this subgroup failed to show an increased number of gene copies by FISH (31%). The incidence of HER2 overexpression (33% and 50%, respectively) and gene amplification (25% and 33%, respectively) among glycogen‐rich and lipid‐rich carcinomas was not higher than that observed in breast cancer generally.

Conclusion:  Our data suggest that preferential involvement of the HER2 gene in micropapillary and apocrine breast carcinomas may contribute to their aggressive behaviour.
Metastasis in pleural mesothelioma. Immunohistochemical markers for disseminated disease
Authors: Lumb P D , Suvarna S K
Published: December 2004

Aims:  To examine 13 cases of mesothelioma with metastases and compare these with 29 biopsy samples of patients without metastases. Metastatic disease was defined as tumour in which tumour appeared in a different cavity/tissue of the body and which showed no direct spread. Consequently, mediastinal nodal and parenchymal lung spread was excluded.

Methods and results:  Standard sections were prepared and stained according to the manufacturers' protocols. The antibodies used were MIB‐1, nm23, Bcl‐2, MMP‐9, EMMPRIN (CD147) and α‐catenin. Scoring employed a grading system (0/1/2/3), and was performed by two pathologists independently. The tissues revealed no significant staining differences for MIB‐1, Bcl‐2, MMP‐9 or EMMPRIN, and therefore no linkage to metastatic potential was determined. α‐Catenin showed a diminished level of expression in cases of metastatic mesothelioma (P = 0.024), possibly reflecting dimished catenin–cadherin binding and paralleling data from other tumours. nm23 showed greater staining in metastatic tumours when compared with the controls (P = 0.001). Intriguingly, the nm23 staining pattern was the reverse of that expected. This reversed pattern has been noted before in other tumours and therefore a biological prognostic event may exist for this antibody test and mesothelioma metastasis.

Conclusion:  There may be a place for nm23 and possibly α‐catenin in immunohistochemical assessment of mesothelioma metastatic potential. However, MIB‐1, Bcl‐2, MMP‐9 and EMMPRIN (CD147) do not show significant staining results.
Expression of stromelysin‐1 (MMP‐3), gelatinase B (MMP‐9), and plasminogen activator system during fetal calvarial development
Authors: Zeitler P , Pahnke J , Marx A
Published: December 2004

Aims:  To investigate whether degrading proteases can be found in patent calvarial sutures. Sutural growth and fusion means replacement of the sutural connective tissue, rich in fibronectin and collagen type V, by expanding calvarial bone. Proliferation of one tissue into the border area of another implies the presence of enzymes able to degrade extracellular matrix (ECM). An important family of proteases is the matrix metalloproteinases (MMPs), as is the plasminogen/plasmin system.

Methods and results:  Expression of two MMPs with substrate specifity for fibronectin and collagen type V and of the plasminogen activator system was studied by immunohistochemistry in samples of human fetal calvariae (age range weeks 19–35 of gestation). In all cases, intense staining for MMPs, urokinase, and urokinase receptor was found in the sutural connective tissue and along the outer and inner borders of calvarial bone.

Conclusions:  Our findings suggest that degradation of sutural connective tissue takes place during sutural growth. This might facilitate proliferation of calvarial bone. Recently, it was shown that an important regulatory mechanism of sutural growth is apoptosis of osteoblasts in the osteogenic front. Intact fibronectin is known to prevent apoptosis of proliferating osteoblasts while fibronectin degradation induces their apoptosis.
Expression of TTF‐1 and cytokeratins in primary and secondary epithelial lung tumours: correlation with histological type and grade
Authors: Jerome Marson V , Mazieres J , Groussard O , Garcia O , Berjaud J , Dahan M , Carles P , Daste G
Published: December 2004

Aims:  To assess cytokeratin (CK) and thyroid transcription factor (TTF)‐1 expression in primary epithelial lung tumours by comparison with non‐pulmonary carcinomas and to correlate it with their histological type and grade.

Methods and results:  Immunohistochemistry using antibodies against CKs 5/6, 7, 19, 20 and TTF‐1 was applied to 165 primary and 37 secondary epithelial lung tumours. CK5/6 is a sensitive and specific marker of lung squamous carcinomas being positive in 100% of cases. CK7 is a common marker of primary lung adenocarcinomas (100% of cases) but with a lower specificity since it is also observed in other primary lung carcinomas (70% of large‐cell neuroendocrine carcinomas, 40% of large‐cell carcinomas, 23% of squamous carcinomas) but also in 27% of non‐pulmonary adenocarcinomas. Addition of an anti‐CK20 may be useful to prove or disprove the pulmonary origin of an adenocarcinoma when there is a history of colon cancer. CK19 is ubiquitous but a predominant or exclusive ‘dot‐like’ pattern is very suggestive of high‐grade neuroendocrine carcinoma. TTF‐1 is a very sensitive and specific marker to document the pulmonary origin of an adenocarcinoma if a thyroid origin is excluded. Its expression in neuroendocrine lung tumours depends on the tumour grade.

Conclusions:  Immunohistochemical expression of CKs and TTF‐1 may be correlated with histological type and grade of lung primary epithelial tumours and may allow them to be distinguished from non‐pulmonary carcinomas.
Increased cell size and Akt activation in HER‐2/neu‐overexpressing invasive ductal carcinoma of the breast
Authors: Sastre‐Garau X , Genin P , Rousseau A , Al Ghuzlan A , Nicolas A , Fréneaux P , Rosty C , Sigal‐Zafrani B , Couturier J , Thiery J‐P , Magdelénat H , Vincent‐Salomon A
Published: December 2004

Aims:  To determine whether cell size is related to HER‐2/neu status and/or to Akt activation in breast carcinomas. HER‐2/neu overexpression is observed in 20–30% of invasive breast carcinomas with poor pronostic features, but little is known about the cell phenotype associated with HER‐2/neu activation. Akt has been found to be involved in the HER‐2/neu signal transduction pathway and Akt activation has been associated with increased cell size in various models.

Methods and results:  A case–control study of invasive ductal carcinoma of the breast was carried out, including 21 cases displaying HER‐2/neu overexpression and 20 HER‐2/neu negative controls. Cytoplasmic and nuclear sizes were measured on digitized histological pictures using cell image analysis software. Akt expression analysis was performed by immunohistochemistry on formalin‐fixed histological sections using an anti‐phosphorylated‐Akt (Ser473) antibody.

Results:  HER‐2/neu‐overexpressing carcinomas had a mean nuclear size of 75 ± 22.2 µm2 and a mean cytoplasmic size of 187 ± 52.3 µm2. Both values were higher than the nuclear and cytoplasmic size of HER‐2/neu‐negative cases (nucleus = 58 ± 24.5 µm2, cytoplasm = 133 ± 56.6 µm2; P = 0.02 and P =0.003, respectively). Up to 75% of the tumours with a cell size over 140 µm2 were HER‐2/neu‐positive. Immunohistochemical Akt expression was observed in 19/40 (47.5%) cases. The immunoreactivity was localized in the cytoplasm in eight cases, on the cell membrane in four cases and at both sites in seven cases. One case was not interpretable. Comparison between HER‐2/neu and Akt status showed that Akt was detectable at the cell membrane in 43% (9/21) of HER‐2/neu‐positive and in 10% (2/19) of HER‐2/neu‐negative cases (P = 0.02).

Conclusions:  HER‐2/neu overexpression was consistently associated with increased cell size in invasive ductal carcinoma of the breast. This increase may be related to concomitant Akt activation. The assessment of activated pathways in HER‐2/neu‐overexpressing breast carcinomas may provide useful information for optimized individual HER‐2/neu‐targeted therapy.
Expression of cholesteryl ester transfer protein (CETP) in germinal centre B cells and their neoplastic counterparts
Authors: Ito K , Ishikawa F , Kanno T , Ishikawa Y , Akasaka Y , Akishima Y , Ishii T , Terayama Y , Sugimoto M , Watanabe T , Mori S
Published: December 2004

Aims:  Cholesteryl ester transfer protein (CETP) is known to facilitate the transfer of lipids between plasma lipoproteins. Previous studies on human tissues have determined that the spleen contains large amounts of CETP mRNA, while the exact location of CETP in such organs remains unknown. In the present study, our aim was to locate CETP protein expression at the cellular level in human normal and neoplastic lymphoid organs.

Methods and results:  In‐situ hybridization (ISH) and immunohistochemistry were applied to pathology specimens. A specific rabbit anti‐CETP antibody was used for immunohistochemical analysis, together with another CETP‐specific monoclonal antibody. A riboprobe for ISH was derived from CETP cDNA. Immunohistochemically, CETP was localized in germinal centre B cells and a proportion of marginal zone B cells. ISH showed that CETP mRNA was located mostly in the same areas. When 141 malignant lymphomas of various subtypes were studied, high expression of CETP, equivalent to that found in normal germinal centre B cells, was demonstrated in lymphoma subtypes that are currently regarded as the neoplastic counterparts of primarily germinal centre B cells.

Conclusion:  CETP localizes B cells in germinal centres, a proportion of post‐germinal centre B cells and their neoplastic counterparts.
Cellular composition of pancreas‐associated lymphoid tissue during human fetal pancreatic development
Authors: Korpershoek E , Leenen P J M , Drexhage H A , De Krijger R R
Published: December 2004

Aim : To study human fetal pancreatic tissue between 15 weeks of gestation and term, analysing the development of pancreatic lymphoid tissue and focusing on the presence and maturational status of dendritic cells (DCs). During normal human fetal pancreatic development lymphoid tissue arises in and around the pancreas. DCs are antigen‐presenting cells which are capable of initiating immunity, but are also essential in inducing and maintaining T‐cell tolerance.

Methods and results : First, the presence and general composition of intra‐ and peripancreatic lymphoid tissue was investigated by histology and immunohistochemistry with antibodies to CD3, CD4, CD8, CD14, CD20, CD68, and CD79. Intrapancreatic lymphoid tissue (IPLT) appeared to be present only from 29 weeks of gestation onwards, and had a similar composition to peripancreatic lymphoid tissue (PPLT), which was found in all 23 specimens examined. Both forms of lymphoid tissue had an architecture similar to lymph nodes, with separate B‐ and T‐lymphocyte areas and scattered macrophages. DCs were investigated in detail by immunohistochemistry for CD1a, CD83, CD86, CD123, Langerin, and DC‐LAMP. Both Langerin, a marker for immature DCs, as well as DC‐LAMP, a marker for mature DCs, were expressed by cells in both the IPLT and PPLT at all ages examined.

Conclusion : The presence of DCs at all developmental stages, expressing various maturation‐related markers, in addition to the general composition of the human fetal PPLT and IPLT suggests that this is fully functional and has a function comparable to peripheral lymph nodes.
Surgical excision is warranted following a core biopsy diagnosis of mucocoele‐like lesion of the breast
Authors: Carder P J , Murphy C E , Liston J C
Published: December 2004

Aims:  Mucocoele‐like lesions (MLLs) of the breast are unusual lesions in which mucin‐filled ducts or cysts are accompanied by extrusion of mucin into surrounding stroma. A possible diagnosis of MLL may be suggested by the finding of mucin‐filled ducts or cysts and/or stromal mucin in a core biopsy sample. Whether such findings should prompt immediate open diagnostic biopsy to exclude malignancy is currently uncertain, although this represents current practice in our institution. In this study we have reviewed 11 cases of possible MLL on core biopsy correlating both pathological and radiological findings in order to determine the risks of associated malignancy and whether excision is the most appropriate management option.

Methods and results:  Eleven cases of possible MLL presenting via the Breast Screening and Assessment Unit in Leeds since April 1999 were identified by review of pathological records. Histological slides, mammograms and ultrasound images were reviewed. Ten of the 11 had undergone open surgical biopsy for diagnosis. Three of the 10 (30%) proved to derive from malignant lesions. Two were ductal carcinoma in situ (DCIS) and one was an invasive mucinous carcinoma. All three cases had an associated atypical epithelial proliferation which, in a surgical excision, would be classified as atypical ductal hyperplasia (ADH) at least, as well as mucin in the core biopsy sample. The majority of possible MLLs presented radiologically as coarse calcification, but two of four (50%) which had a radiological mass subsequently proved malignant. Seven cases were without atypia on the core and all subsequently proved benign. Three of these, however, were associated with ADH on the excision biopsy.

Conclusion:  Surgical excision is warranted following a core biopsy suggestion of possible MLL when mucin‐filled ducts or cysts and stromal mucin have been seen. The risk of malignancy is high when the core biopsy also contains an atypical epithelial proliferation (100% in our series) and also when there is an associated radiological mass lesion. In cases without atypia on the core a significant proportion of cases (43%) are associated with ADH on excision.
The spectrum of pathological changes in severe acute respiratory syndrome (SARS)
Authors: Cheung O Y , Chan J W M , Ng C K , Koo C K
Published: December 2004

Aims:  To analyse the lung pathology of severe acute respiratory syndrome (SARS) and correlate the findings with the time sequence of the disease.

Methods and results:  Ten patients with a clinical diagnosis of SARS, and virological confirmation of SARS coronavirus infection were identified. Histology in most cases showed diffuse alveolar damage, from early to late phases, and the changes corresponded to the time sequence. Other variable features include multinucleated giant cells, pneumocytes with cytomegaly and variable amounts of inflammatory cells and foamy macrophages. One case showed superimposed bronchopneumonia. No viral inclusions were found. Coronavirus particles were identified in pneumocytes by electron microscopy.

Conclusions:  The predominant pathological process of SARS is diffuse alveolar damage and, in patients who die from the disease, there is evidence of organization and fibrosis. There are apparently no histological features specific for this disease, and the aetiological diagnosis depends on virological and ultrastructural studies.
Vasculitis in lichen sclerosus: an under recognized feature?
Authors: Regauer S , Liegl B , Reich O , Beham‐Schmid C
Published: December 2004

Aims : To analyse 90 vulvar and 72 penile cases of lichen sclerosus (LS) on haematoxylin and eosin sections for vascular changes and the vascular infiltrates immunohistochemically with antibodies to T cells, B cells and antigen‐presenting dendritic cells. LS is a skin disease of presumed autoimmune origin. Autoimmune diseases are mediated by lymphocytes which occasionally produce a lymphocytic vasculitis.

Methods and results : Three types of lymphocytic infiltrates were identified: (i) perivascular lymphocytic infiltrates without damage to vessel walls; (ii) lymphocytic vasculitis in three forms: (a) concentric lymphohistiocytic infiltrates with lamination of the adventitia by basement membrane material which was typical for penile LS; (b) lymphocytic vasculitis with dense perivascular lymphocytic cuffing with occasional fibrin deposition in vessel walls and subendothelial lymphocyte infiltration, quite common in vulvar LS; and (c) intramural lymphocytic infiltrates in large muscular vessels; (iii) leukocytoclastic vasculitis in LS was exceptionally rare. In lymphocytic vasculitis, CD20+ B cells, CD4+ T cells and dendritic cells were the principal infiltrating cells.

Conclusions : Dendritic cells capture (foreign) antigens after entry into the affected tissues and initiate immune responses acting as a matrix on which antigen‐specific T and B cells interact. The described vascular features are indicative of antigen‐mediated vasculitic changes in LS.
British Division of the International Academy of Pathology
Authors: Van Den Tweel J , Howat A J , Shepherd N A , Francis N , Harris C
Published: December 2004

Forthcoming meetings

Spring 2004 Symposium on Dermatopathology. Brussels, Belgium

10‐‐15 October 2004 XXVth International Congress. Brisbane, Australia

26‐‐27 November 2004 Symposium on Pulmonary Pathology. London, UK
Liposclerosing myxofibrous tumour: a traumatized variant of fibrous dysplasia? Report of four cases and review of the literature
Authors: Heim‐Hall J M , Williams R P
Published: December 2004

Aims : To describe the pathological and radiological features of four cases of liposclerosing myxofibrous tumour (LSMFT). LSMFT is a benign fibro‐osseous lesion of bone with a marked predilection for the intertrochanteric region of the proximal femur. It is characterized by a complex mixture of histological elements including fibrous dysplasia‐like bony trabeculae, myxofibrous tissue, lipomatous areas, xanthoma cells and pseudo‐Paget's bone. This lesion is not a universally accepted pathological entity and often appears in the literature under variants of fibrous dysplasia or other benign lytic bone lesions.

Methods and results : All lesions exhibited histological and/or radiological overlap with fibrous dysplasia. A relationship to trauma was noted in three of the cases. The hypothesis that these lesions represent a traumatized variant of fibrous dysplasia was explored. After reviewing the biomechanics of the proximal femur, a possible relationship between predilection of LSFMT for this anatomical region and increased susceptibility to fracture was noted.

Conclusions : We hypothesize that when fibrous dysplasia involves the proximal femur, it makes the bone more susceptible to fatigue fracture, thereby altering its histological appearance. The wide variety of histological patterns in LSMFT could represent the end result of repeated reaction to fatigue stresses.
Mucin expression in peripheral airways of patients with chronic obstructive pulmonary disease
Authors: Caramori G , Di Gregorio C , Carlstedt I , Casolari P , Guzzinati I , Adcock I M , Barnes P J , Ciaccia A , Cavallesco G , Chung K F , Papi A
Published: December 2004

Aims:  To study the expression of mucins in peripheral airways in patients with chronic obstructive pulmonary disease (COPD).

Methods and results:  Peripheral lung sections from smokers with COPD (n = 9) and age‐matched controls including smokers (n = 11) and lifelong non‐smokers with normal lung function (n = 6) were stained with alcian blue, periodic acid–Schiff (PAS) and by immunohistochemistry of mucins (MUC): MUC2, MUC4, MUC5AC, MUC5B and MUC6. Histochemical staining and immunoreactivity of bronchiolar epithelium were graded and the presence or absence of stained mucus in the bronchiolar lumen was evaluated. There were no differences in alcian blue and PAS epithelial staining between the three groups. Intraluminal PAS staining was significantly more frequent among COPD subjects (P < 0.05). The expression of MUC5AC was significantly higher in the bronchiolar epithelium of patients with COPD (P < 0.05). Within the bronchiolar lumen, the predominant mucin was MUC5B. Intraluminal MUC5B was significantly more frequent among COPD patients (P < 0.05).

Conclusions:  COPD is specifically associated with increased expression of MUC5B in the bronchiolar lumen and of the mucin MUC5AC in the bronchiolar epithelium. These changes in mucin production in the peripheral airways may contribute to the pathophysiology of COPD.
Cellular retinol‐binding protein‐1 expression in endometrial stromal cells: physiopathological and diagnostic implications
Authors: Orlandi A , Ferlosio A , Ciucci A , Sesti F , Lifschitz‐Mercer B , Gabbiani G , Spagnoli L G , Czernobilsky B
Published: December 2004

Aims:  Cellular retinol‐binding protein‐1 (CRBP‐1) contributes to the maintenance of the differentiated state of the endometrium through retinol bioavailability regulation. The aim was to analyse CRBP‐1 expression in endometrial stromal cells at eutopic and ectopic sites in different physiopathological conditions.

Methods and results:  Antibodies to CRBP‐1, CD10 and α‐smooth muscle actin were applied to proliferative (n = 10), secretory (n = 9) and atrophic (n = 7) endometrium, decidua (n = 4), adenomyosis (n = 5), endometriosis (n = 10), endometrial polyps (n = 9), simple endometrial hyperplasia (n = 6), well‐differentiated endometrioid carcinoma (n = 6) and submucosal leiomyomas (n = 5). In some cases, Western blotting and reverse transcription‐polymerase chain reaction were also applied. CRBP‐1 was expressed by eutopic and ectopic endometrial stromal cells more markedly during the late secretory phase and in decidua of pregnancy. CRBP‐1 expression was low in the stroma of atrophic endometrium and absent in myometrium, leiomyomas and cervical stroma. CD10 immunoreactivity was weak in atrophic endometrium and in decidua.

Conclusions:  CRBP‐1 expression characterizes endometrial stromal cells at eutopic and ectopic sites and appears to be more specific than CD10. The level of CRBP‐1 varies in intensity according to hormonal variations, reaching its maximum in predecidua and decidua. Thus, immunodetection of CRBP‐1 may help to elucidate the physiopathological changes which occur in endometrial stroma and can also be applied as an adjuvant stromal marker.
Lingual alveolar soft part sarcoma; 14 cases: novel clinical and morphological observations
Authors: Fanburg‐Smith J C , Miettinen M , Folpe A L , Weiss S W , Childers E L B
Published: December 2004

Aims:  Alveolar soft part sarcoma (ASPS) is a rare sarcoma in the buttocks or thigh of young adults, often with metastases to lung, brain, or bone. This study examines the morphological and clinical features of lingual ASPS.

Methods and results:  Fourteen cases, in eight males and six females (ages 3–21 years, median 5 years), ranged from 8 to 50 mm, median 25 mm. All tumours were intramuscular, circumscribed and multinodular. Tumours from all but the oldest patient exhibited a predominantly solid (non‐alveolar) growth pattern. Vascular invasion was common. Crystals varied in number from none or extremely rare to nearly 100% of tumour cells.

Immunohistochemical results:  Fifty percent desmin positive, all focally smooth muscle antigen (SMA) positive; negative for vimentin, neural/melanocytic, myoid, histiocytic, and epithelial markers. All tumours were surgically excised; only two patients received chemotherapy. Follow‐up on 10 patients showed that all patients were alive without disease (4–32, median 22 years). Only one patient had a microscopic metastasis to lung (3 years) but was without disease at 11 years.

Conclusions:  Lingual ASPS is a tumour of childhood with a distinctive, predominantly solid growth pattern. Despite typical vascular invasion, the early diagnosis and small tumour size may explain its relatively good outcome.
Effect of an inhibitor of Jun N‐terminal protein kinase, SP600125, in single allergen challenge in sensitized rats
Authors: Eynott Paul R. , Xu Li , Bennett Brydon L. , Noble Alistair , Leung Sum‐Yee , Nath Puneeta , Groneberg David A. , Adcock Ian M. , Chung K. Fan
Published: December 2004

Jun N‐terminal kinase (JNK) has been implicated in the pathogenesis of inflammatory diseases including asthma. We examined the effect of SP600125 (anthra [1,9‐cd] pyrazol‐6 (2H)‐one), a novel inhibitor of JNK in a model of asthma. Brown‐Norway rats were sensitized to ovalbumin and treated with SP600125 intraperitoneally (90 mg/kg in total). SP600125 inhibited allergen‐induced, increased activity of phosphorylated c‐jun but not of phosphorylated‐MAPKAPK2, indicative of activation of p38 MAPK, in the lung. SP600125 inhibited macrophage (P < 0·04), lymphocyte (P < 0·05), eosinophil (P < 0·04) and neutrophil (P < 0·005) numbers in bronchoalveolar lavage. Eosinophil and T‐cell accumulation in the airways, mRNA expression for interleukin‐1β, tumour necrosis factor‐β, interleukin‐3, interleukin‐4 and interleukin‐5, serum levels of allergen‐specific immunoglobulin E and bronchial hyperresponsiveness were not affected by SP600125. Selective inhibition of JNK reduced inflammatory cell egress into the airway lumen after single allergen exposure. The role of JNK mitogen‐activated protein kinase activation may be limited in the pathogenesis of bronchial hyperresponsiveness after single allergen exposure.
Compound heterozygosity for Pten and SHIP augments T‐dependent humoral immune responses and cytokine production by CD4+ T cells
Authors: Moody J. L. , Jirik F. R.
Published: December 2004

Tight regulation of the phosphatidylinositiol 3‐kinase (PI3K) pathway is essential not only for normal immune system development and responsiveness, but also in the prevention of immunopathology. Indeed, unchecked activation of the PI3K pathway in T cells induces lymphoproliferation and systemic autoimmunity. Evaluating the importance of threshold levels of two key PI3K pathway phosphoinositol phosphatases, we previously reported that mice heterozygous for both Pten and SHIP develop a more rapid progression of a lymphoproliferative autoimmune syndrome than do Pten+\− mice. Investigating the basis for this difference, we now describe a quantitative and qualitative difference in the antibody responses of C57BL\6 Pten+\− SHIP+\− mice upon challenge with a T‐dependent antigen. Suspecting that this phenotypic difference might be the result, at least in part, of a T‐helper cell defect, an in vitro analysis of anti‐CD3/interleukin (IL)‐2‐expanded CD4+ T cells was performed. After stimulation with anti‐CD3, cells from mice heterozygous for both Pten and SHIP exhibited a striking increase in IL‐4 secretion (> 10‐fold), without a corresponding increase in T helper 2 (Th2) cell numbers being evident by intracellular staining for this cytokine. Modest increases were also seen for both IL‐13 and IFN‐γ. Perhaps in keeping with this abnormal in vitro cytokine profile, IgG1 serum levels were significantly elevated in young C57BL\6 Pten+\− SHIP+\− mice. Thus, the relative levels of Pten and SHIP appear to be key variables in CD4+ T‐cell function, primarily via their ability to regulate IL‐4 production.
Detection of acid diffusion through bovine dentine after adhesive application
Authors: Hiraishi N. , Kitasako Y. , Nikaido T. , Foxton R. M. , Tagami J. , Nomura S.
Published: December 2004

Aim  Acidic diffusion through bovine dentine was investigated by measuring pH changes on dentine surfaces after applying three adhesive systems.

Methodology  Coronal incisor bovine dentine discs, 0.5 mm thick, were prepared from dentine close to the pulp chamber. A single‐bottle adhesive system‐Single Bond, a self‐etching primer system‐Clearfil SE Bond and an ‘all‐in‐one’ adhesive system‐AQ Bond were used. The labial dentine surfaces were conditioned as follows: Single Bond groups: (SB‐1) 35% phosphoric acid etchant was applied and left in place; (SB‐2) the etchant was applied for 15 s and rinsed off for 10 s; (SB‐3) application of adhesive agent and light curing following step SB‐2; Clearfil SE Bond groups: (SE‐1) SE primer was applied for 20 s and dried; (SE‐2) application of adhesive agent and light curing following step SE‐1; AQ Bond groups: (AQ‐1) AQ Bond adhesive was applied for 20 s and dried, applied for additional 5 s and dried again; (AQ‐2) light curing following step AQ‐1. The pH change on the pulpal dentine surface was measured using a pH‐imaging microscope.

Results  All the Single Bond groups revealed a lower pH on the pulpal surface (pH 6.25, 6.59 and 6.64 for SB‐1, SB‐2 and SB‐3, respectively) compared with intact dentine. Clearfil SE Bond and AQ Bond groups showed no significant deference in pH value from intact dentine.

Conclusions  Acid diffusion from phosphoric acid etching was observed when placed on 0.5 mm‐thick dentine discs; however, there was only limited evidence of acid diffusion from SE primer and AQ Bond.
Electronic apex locators
Authors: Gordon M. P. J. , Chandler N. P.
Published: December 2004

Prior to root canal treatment at least one undistorted radiograph is required to assess canal morphology. The apical extent of instrumentation and the final root filling have a role in treatment success, and are primarily determined radiographically. Electronic apex locators reduce the number of radiographs required and assist where radiographic methods create difficulty. They may also indicate cases where the apical foramen is some distance from the radiographic apex. Other roles include the detection of root canal perforation. A review of the literature focussed first on the subject of electronic apex location. A second review used the names of apex location devices. From the combined searches, 113 pertinent articles in English were found. This paper reviews the development, action, use and types of electronic apex locators.
Intralesional isotype profiles in human localized cutaneous leishmaniasis lesions
Authors: Aragort De Rossell Raiza , Calcagno Marina , Rossell Osmán , Maizo De Segnini Zulay , Rodríguez Ana María
Published: December 2004

This immunocytochemical study evaluates the presence of IgG1–4, IgA and IgE immunoglobulins in active lesions of 25 localized cutaneous leishmaniasis patients from three bioclimatic areas (Awa, Afa and Bsha) in Mérida State, Venezuela. All immunoglobulin isotypes except IgE were detected, with variable intensity, in one or more of the epidermal or dermal components of skin lesions. IgG1 and IgG2 were detected significantly more frequently than IgG3, IgG4 and IgA. The ranking of the isotypes according to frequency of detection was the same in all areas: IgG1 = IgG2 > IgG3 = IgG4 = IgA, but considered as whole, all isotypes were detected significantly more frequently in patients from the Awa area than in those from the Bsha area. The predominant expression of isotypes IgG1 and IgG2 suggests a preferential Th1 like immune response. Anti‐Leishmania immunoserum stained only parasites and their debris, suggesting that most of the immunostaining was nonspecific.
A soluble fibre gel produced from rice bran and barley flour as a fat replacer in Asian foods
Authors: Inglett George E. , Carriere Craig J. , Maneepun Saipin , Tungtrakul Patcharee
Published: December 2004

A hydrocolloidal fibre composite made from rice bran and barley flour, called Ricetrim, was found to have similar rheological properties to coconut cream. Coconut cream displayed a very narrow region of linear viscoelastic behaviour, both above and below strain values of 0.1%, the oscillatory shear modulus dropped sharply with increasing strain, indicating non‐linear viscoelastic behaviour. This region of linear viscoelastic behaviour extended to strains of 10%. When Ricetrim was substituted for coconut cream in Thai foods, it was found to produce acceptable products, but with lower saturated fat contents. Cookies, pumpkin pudding, layer cake, dip for pot crust, taro custard and sauté chicken curry were produced with fat contents reduced by 47.8, 94.3, 59.8, 75.3, 61.3 and 60.6%, respectively. Some differences in flavour and texture were observed at the higher levels of substitution, but these differences appeared to present only small changes in the overall score of general acceptability, or suitability, of the fibre gel foods. Scanning electron micrographs of the pumpkin pudding revealed only small changes in their surfaces with Ricetrim addition, even at higher levels of substitution.
Statistical evaluation of different technological and rheological tests of Polish wheat varieties for bread volume prediction
Authors: Konopka Iwona , Fornal Łucja , Abramczyk Danuta , Rothkaehl Jadwiga , Rotkiewicz Daniela
Published: December 2004

Forty‐two Polish wheat flour were used to establish correlation coefficients between protein content, Zeleny test, falling number value, amylograph viscosity, farinograph water absorption, bread volume and rheological properties of dough, as shown by use of a extrusion chamber and alveograph. The equations expressing the changes of bread volume and flour water absorption as a function of significantly correlated parameters were calculated. The correlations and their significance depended on wheat quality and the alveographic parameters were significantly correlated with the dough extrusion parameters. The dough extrusion parameters were significantly correlated only with the water absorption of soft wheats. The dough rheological tests were correlated to a greater extent with the values of the Zeleny test than to the protein content. The prediction of the bread volume as a function of flour quality parameters and dough rheological properties was best done by grouping wheat varieties into specific qualitative classes.
Successional patterns on pen shell communities at local and regional scales
Authors: Munguia Pablo
Published: December 2004

I present a successional study of marine organisms on pen shells (Atrina rigida) at different regions of St Joe Bay, Florida. By incorporating measures of relative abundance and assembly time I show how the relationship between local and regional diversity develops through different successional stages.

The results showed that, with time, motile species richness increases significantly while evenness indices remain high and constant. Sessile species, on the other hand, increased in both species richness and evenness through time.

For the motile species, regions seem to remain different while local saturation is observed. These results suggest that this group is under species‐sorting: species are mobile enough that recruits and adult dispersal within a region maintain differences among regions, while local communities are saturated.

For the sessile species, the local–regional relationship was unsaturated at all sampling dates with both untransformed and rarefied data. Regions are initially similar in community structure, then differ through time to become similar again at the last sampling date. This may reflect a priority effect: propagules that arrive at a shell may initially exert influence on the species composition on a shell, so that at intermediate sampling times regions differ in community structure. However, at the last sampling there were no differences detected among regions, suggesting that dispersal distances might be larger for this group of species.

These results suggest the following. (1) The degree of species saturation will depend on the successional stage of a community. (2) Incorporating species abundances (i.e. through rarefaction or other techniques) demonstrates the role of species commonness or rarity in determining patterns of community diversity at different scales. (3) Depending on the group of species studied, the size of the region will vary and will influence the local–regional dynamics: the perceived region for sessile species may be larger than for motile species.
Age of primiparity and implications of early reproduction on life history in female Columbian ground squirrels
Authors: Neuhaus P. , Broussard D. R. , Murie J. O. , Dobson F. S.
Published: December 2004

Factors leading to differences in age of primiparity and possible life‐history implications arising from these differences were studied in a population of Columbian ground squirrels (Spermophilus columbianus; Ord, 1815). We used data collected from 1992 to 2000 on two neighbouring colonies of ground squirrels in south‐eastern Alberta, Canada.

Earlier born females were more likely to wean successfully a litter at the age of 2. Among 2‐year‐old females, those who emerged earlier and heavier from hibernation were more likely to wean offspring than those females who emerged later and lighter from hibernation. The presence of the mother had a significant positive impact on reproductive output in 2‐year‐old females.

Although there was a positive correlation between lifetime reproductive success and age at death, there was no difference in lifetime reproductive success or in age at death, depending on age of primiparity. For individual females, litter size at weaning at 2 years old did not differ from that at 3 years old.

We conclude that body condition, presence or absence of the mother and environmental conditions are the main factors leading to differences in age of first successful reproduction in Columbian ground squirrels. Previous breeding experience does not seem to play a role in determining reproductive success. Finally, differences in age of first successful reproduction do not seem to have an effect on lifetime reproductive success or longevity.
Dietary macro‐ and micronutrient intakes of nonsupplemented pre‐ and postmenopausal women with a perspective on menopause‐associated diseases1
Authors: Massé P. G. , Dosy J. , Tranchant C. C. , Dallaire R.
Published: December 2004

Objectives  To assess the dietary intakes and diet quality of menopausal women relative to premenopausal women, and to determine whether their diets are compatible with reducing risks of cardiovascular disease (CVD) and osteoporosis.

Design  Cross‐sectional study using 3‐day food records and anthropometric measurements.

Subjects  Thirty apparently healthy, nonoestrogen using and nonsupplemented women menopausal since 3–5 years and 30 well‐matched premenopausal women.

Outcome measures  Nutrient intakes, diet nutrient density, body mass index (BMI), waist circumference, waist‐to‐hip ratio and serum oestradiol.

Results  Energy intake and body weight of pre‐ and postmenopausal women were comparable. Their BMI, waist circumference and waist‐to‐hip ratios were within healthy ranges. The diet of postmenopausal women was compatible (less total lipids and saturated fatty acids; more fibres, antioxidant vitamins and potassium) with North American nutritional recommendations linked to cardiovascular health. Their dietary iron intakes exceeded their reduced physiological need, which may jeopardize their cardiovascular system. Their calcium and vitamin D intakes were far below recommendations for healthy bones. Five other nutrients were also suboptimal. Phosphorus intake (high in both groups) correlated with dietary proteins, sulphur amino acids and calcium.

Conclusions  The diet of the postmenopausal women studied were more compatible with national nutritional recommendations than that of premenopausal controls. However, these postmenopausal women, not taking hormone replacement therapy (HRT) and having inadequate dietary calcium and vitamin D intakes, may be at increased risk of osteoporotic fracture later in life. More studies on CVD risk inherent to body iron accumulation involving a large number of postmenopausal women are warranted before planning public health measures regarding dietary iron intake.
Urinary iodine and thyroid volume in a Swedish population
Authors: Milakovic M. , Berg G. , Nyström E. , Lindstedt G. , Gebre‐Medhin M. , Eggertsen R.
Published: December 2004

Objective.  To evaluate the present efficacy of an iodine supplementation programme working in Sweden since 1936 by studying the iodine excretion in urine and determining the thyroid volume in a population in a semi‐rural community.

Design.  A cross‐sectional population screening comprising three age groups with randomly selected individuals: group 1 (children): 7–9 years, n = 61 (invited 70); group 2 (teenagers): 15–17 years, n = 61 (invited 63), and group 3 (adults): 60–65 years; n = 57 (invited 73).

Main measurements.  Urinary iodine was measured spectrophotometrically; thyroid volume by ultrasonography.

Results.  The median values for urinary iodine concentration in the three age groups were 194 μg L−1, 246 μg L−1 and 190 μg L−1, respectively, indicating an adequate iodine intake. In the 7–9 year olds, the median value of the thyroid volume was 4.7 mL, which coincides with the recently established upper limit of normal children of that age, 4.0–4.8 mL (ICCIDD, International Council for control iodine deficiency disorders). One eight‐year‐old boy had a pronounced goiter. Four teenagers and one adult were found to have an enlarged thyroid gland according to earlier established reference volumes (15 years >16 mL; adults > 25 mL).

Conclusion.  We conclude that the iodine intake in our region is sufficient in age groups ranging from young children to pre‐retirement adults.
Genetic evaluation of a proposed introduction: the case of the greater prairie chicken and the extinct heath hen
Authors: Palkovacs Eric P. , Oppenheimer Adam J. , Gladyshev Eugene , Toepfer John E. , Amato George , Chase Thomas , Caccone Adalgisa
Published: December 2004

Population introduction is an important tool for ecosystem restoration. However, before introductions should be conducted, it is important to evaluate the genetic, phenotypic and ecological suitability of possible replacement populations. Careful genetic analysis is particularly important if it is suspected that the extirpated population was unique or genetically divergent. On the island of Martha's Vineyard, Massachusetts, the introduction of greater prairie chickens (Tympanuchus cupido pinnatus) to replace the extinct heath hen (T. cupido cupido) is being considered as part of an ecosystem restoration project. Martha's Vineyard was home to the last remaining heath hen population until its extinction in 1932. We conducted this study to aid in determining the suitability of greater prairie chickens as a possible replacement for the heath hen. We examined mitochondrial control region sequences from extant populations of all prairie grouse species (Tympanuchus) and from museum skin heath hen specimens. Our data suggest that the Martha's Vineyard heath hen population represents a divergent mitochondrial lineage. This result is attributable either to a long period of geographical isolation from other prairie grouse populations or to a population bottleneck resulting from human disturbance. The mtDNA diagnosability of the heath hen contrasts with the network of mtDNA haplotypes of other prairie grouse (T. cupido attwateri, T. pallidicinctus and T. phasianellus), which do not form distinguishable mtDNA groupings. Our findings suggest that the Martha's Vineyard heath hen was more genetically isolated than are current populations of prairie grouse and place the emphasis for future research on examining prairie grouse adaptations to different habitat types to assess ecological exchangeability between heath hens and greater prairie chickens.
Evidence of genetic selection for growth in new recruits of a marine fish
Authors: PLANES S. , ROMANS P.
Published: December 2004

A cohort of Diplodus sargus, a coastal marine fish abundant in the Mediterranean Sea, has been surveyed from its settlement following the pelagic larval stage up to 4 months of age, when the juveniles are moving to adult habitats in order to assess selective processes. We followed the mortality by looking at the decrease in population abundance and, simultaneously, the genetic structure using allozymes and the growth associated with each genotype to test for a relationship between genotype and phenotype. The recruitment survey demonstrated that 80% of individuals arrived within a single night and that they show very similar age providing a discrete pulse of new recruits that we followed for changes in survival and allele frequencies. After 4 months, there was a total mortality of 80.8%, with the disappearance of 181 of 224 fish that initially colonized the rocky barrier. The decrease in number followed a logarithmic model with a maximum decrease in the early period (first 30 days). The model derived from the 4 months of data demonstrates that most of the mortality in the cohort occurs over the first 120 days following settlement and the model predicted a final abundance of 10 individuals after 1 year. Within the same period of 4 months, we observed significant decrease in multilocus heterozygosity. Such a decrease in heterozygosity partly resulted from a purge of the Pgm‐80* allele. Together with this major change in a natural population, an aquarium experiment demonstrated that individuals with Pgm‐80* alleles show significantly lower growth than other new recruits. We propose that the decrease in frequency of Pgm‐80* in the natural environment is the result of targeted predation that eliminates smaller individuals and therefore individuals bearing Pgm‐80*. The potential metabolic effect as well as a scenario that could lead to the maintenance of polymorphism is discussed.