bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased expression of HMGA1 correlates with tumour invasiveness and proliferation in human pituitary adenomas
Authors: Wang Elaine Lu , Qian Zhi Rong , Rahman Md Mustafizur , Yoshimoto Katsuhiko , Yamada Shozo , Kudo Eiji , Sano Toshiaki 
Published: March 2010

Wang E L, Qian Z R, Rahman M M, Yoshimoto K, Yamada S, Kudo E & Sano T  (2010) Histopathology56, 501–509 Increased expression of HMGA1 correlates with tumour invasiveness and proliferation in human pituitary adenomas Aims:  High‐mobility group A1 (HMGA1) is highly expressed in various benign and malignant tumours. The development of pituitary adenoma in Hmga1 transgenic mice has been reported. However, no studies have investigated HMGA1 expression and its clinical significance in human pituitary adenomas.Methods and results:  Immunohistochemical expression of HMGA1 was analysed with respect to various clinicopathological factors in 95 pituitary adenomas. Nuclear expression of HMGA1 was observed in 62% of pituitary adenomas, whereas normal adenohypophysial tissues were negative. Although HMGA1 expression was frequently detected in clinically non‐functioning adenomas – 90% of silent adrenocorticotropic hormone (ACTH), 76.2% of follicle‐stimulating hormone/luteinizing hormone and 100% of null cell adenomas – it was also detected in 48.1% of growth hormone (GH), 60% of mixed GH/prolactin (PRL), 62.5% of PRL, 66.6% of thyroid‐stimulating hormone and 37.5% of ACTH adenomas. HMGA1 expression was significantly higher in invasive adenomas or macroadenomas than in non‐invasive adenomas or microadenomas (invasive versus non‐invasive, P < 0.05; macroadenoma versus microadenoma, P < 0.05). In addition, HMGA1 showed the highest level in grade IV, more aggressive pituitary adenomas, than in grades I, II and III (IV versus I, P = 0.01; IV versus II, P = 0.01; IV versus III, P = 0.07). Furthermore, a significant correlation between HMGA1 expression and MIB‐1 labelling index was observed (R = 0.368, P < 0.0002).Conclusions:  These findings suggest that HMGA1 up‐regulation has an important oncogenic role in pituitary tumorigenesis, as well as being a novel molecular marker of tumour proliferation and invasiveness.
Expression of L1CAM, COX‐2, EGFR, c‐KIT and Her2/neu in anaplastic pancreatic cancer: putative therapeutic targets?
Authors: Bergmann Frank , Moldenhauer Gerhard , Herpel Esther , Gaida Matthias M , Strobel Oliver , Werner Jens , Esposito Irene , Müerköster Susanne Sebens , Schirmacher Peter , Kern Michael A 
Published: March 2010

Bergmann F, Moldenhauer G, Herpel E, Gaida M M, Strobel O, Werner J, Esposito I, Sebens Müerköster S, Schirmacher P & Kern M A (2010) Histopathology56, 440–448 Expression of L1CAM, COX‐2, EGFR, c‐KIT and Her2/neu in anaplastic pancreatic cancer: putative therapeutic targets?Aims:  Undifferentiated (anaplastic) pancreatic cancer and undifferentiated pancreatic carcinoma with osteoclast‐like giant cells (giant cell tumour) are rare variants of pancreatic ductal adenocarcinoma. Representing biologically highly aggressive neoplasms, they are frequently diagnosed at an advanced stage. The response to established chemo‐ or radiochemotherapeutic treatment regimens is poor, and undifferentiated pancreatic cancer generally has a dismal prognosis. As additional therapeutic options have not yet been investigated in undifferentiated pancreatic cancer, the aim was to analyse the expression of putative therapeutic targets that have shown promising results in various other neoplasms.Methods and results:  Fifteen cases of undifferentiated pancreatic cancer (seven containing osteoclast‐like giant cells) were investigated clinicopathologically and immunohistochemically for putative therapeutic targets. Whereas L1CAM, cyclooxygenase (COX)‐2 and epidermal growth factor receptor (EGFR) were found to be significantly expressed in 80%, 93% and 87% of the investigated tumours, respectively, there was no substantial expression of c‐kit (CD117) and there was no detectable expression of Her2/neu.Conclusions:  The expression of L1CAM, COX‐2 and EGFR in the majority of undifferentiated pancreatic carcinomas suggests that they might represent targets for adjuvant therapy in anaplastic pancreatic cancer. On the other hand, c‐kit and Her2/neu seem to have no relevance for the therapy of these tumours.
Physiological hepatic nuclear vacuolation—how long does it persist?
Authors: Levene Adam P , Goldin Robert D 
Published: March 2010

Levene A P & Goldin R D (2010) Histopathology56, 426–429 Physiological hepatic nuclear vacuolation—how long does it persist?Aims:  Nuclear vacuolation\glycogenation is a characteristic histological feature of non‐alcoholic fatty liver disease (NAFLD) that can help distinguish it from alcohol‐induced liver disease. There are, however, other associations of nuclear vacuolation of which the commonest is as a normal feature of childhood. The aim of this study was to identify how long this physiological nuclear vacuolation persists.Methods and results:  Liver biopsy specimens from 872 patients with chronic hepatitis B virus infection (a condition known not to be associated with nuclear vacuolation) were studied to assess the frequency of nuclear vacuolation at different ages. All the patients studied had a body mass index of <25 kg/m2 and an alcohol intake of <15 units/week, as well as no other risk factors for liver disease. It was found that the frequency of nuclear vacuolation, in the absence of NAFLD, fell from 13% at age 20–24 years to 4% in the early 30s and to 0% at age 60–64 years.Conclusions:  Physiological hepatic nuclear vacuolation is common in the 20s and persists into the 30s. This knowledge can help in the assessment of liver biopsy specimens in which nuclear vacuolation is a feature.
Determination of HER2 amplification in primary breast cancer using dual‐colour chromogenic in situ hybridization is comparable to fluorescence in situ hybridization: a European multicentre study involving 168 specimens
Authors: García‐Caballero Tomás , Grabau Dorthe , Green Andrew R , Gregory John , Schad Arno , Kohlwes Elke , Ellis Ian O , Watts Sarah , Mollerup Jens 
Published: March 2010

García‐Caballero T, Grabau D, Green A R, Gregory J, Schad A, Kohlwes E, Ellis I O, Watts S & Mollerup J (2010) Histopathology56, 472–480 Determination of HER2 amplification in primary breast cancer using dual‐colour chromogenic in situ hybridization is comparable to fluorescence in situ hybridization: a European multicentre study involving 168 specimensAims:  Fluorescence in situ hybridization (FISH) can be used to reveal several genomic imbalances relevant to proper cancer diagnosis and to the correct treatment regime. However, FISH requires expensive and advanced fluorescence microscopes in addition to expertise in fluorescence microscopy. To determine whether a newly developed dual‐colour chromogenic in situ hybridization (CISH) method is a suitable alternative to FISH, we analysed the human epidermal growth factor receptor 2 gene (HER2) amplification level of 168 breast cancer specimens using dual‐colour CISH and FISH and compared the results.Methods and results:  We found 100% agreement between HER2 status determined by FISH and dual‐colour CISH. Furthermore, we observed that the time used to score slides was significantly reduced by 28% in dual‐colour CISH compared with the FISH protocol. Concordance between HER2 protein status and dual‐colour CISH or FISH was equally good with an overall agreement of 96.8%. Correlation between the HER2/centromere 17 gene ratios obtained with dual‐colour CISH and FISH was highly significant with an overall correlation coefficient (ρ) of 0.96.Conclusions:  We conclude that dual‐colour CISH and bright field microscopy are excellent alternatives to FISH when analysing the HER2 status of primary breast cancer.
Microvascular irregularities are associated with composition of squamous epithelial lesions and correlate with subepithelial invasion of superficial‐type pharyngeal squamous cell carcinoma
Authors: Fujii Satoshi , Yamazaki Manabu , Muto Manabu , Ochiai Atsushi 
Published: March 2010

Fujii S, Yamazaki M, Muto M & Ochiai A (2010) Histopathology56, 510–522 Microvascular irregularities are associated with composition of squamous epithelial lesions and correlate with subepithelial invasion of superficial‐type pharyngeal squamous cell carcinoma Aims:  Superficial squamous epithelial lesions of the pharynx are increasingly recognized by architectural changes in the intraepithelial papillary capillary loop (IPCL) assessed by narrow‐band imaging (NBI). The aim was to explore the histology of squamous epithelial precursor lesions and superficial‐type pharyngeal squamous cell carcinoma (STPSCC), including squamous cell carcinoma (SCC) in situ and early invasive SCC, by focusing on microvascular irregularities to investigate the composition of those lesions and to explore the pathological characteristics of STPSCCs.Methods and results:  Several pathological factors including thickness of intraepithelial squamous cell carcinoma (IESCC) and tumour thickness and microvascular density (MVD) were examined in 104 STPSCCs from 69 patients. The results show that architectural change of IPCL was recognized in precursor lesions in parallel with architectural disturbance and cytological atypia for criteria of diagnosing dysplasia. In 104 STPSCCs, the MVD of IESCC was correlated with the thickness of IESCC (P = 0.0115). Moreover, invasive SCC showed significantly higher MVD of IESCC (P = 0.0078) and there was significant correlation between the thickness of IESCC and subepithelial invasion (P < 0.0001).Conclusions:  Microvascular irregularities are an important pathological factor in carcinogenesis and early invasiveness of SCC of the pharynx.
Identifying HIV infection in diagnostic histopathology tissue samples – the role of HIV‐1 p24 immunohistochemistry in identifying clinically unsuspected HIV infection: a 3‐year analysis
Authors: Moonim Mufaddal T , Alarcon Lida , Freeman Janet , Mahadeva Ula , Van Der Walt Jon D , Lucas Sebastian B 
Published: March 2010

Moonim M T, Alarcon L, Freeman J, Mahadeva U, van der Walt J D & Lucas S B (2010) Histopathology56, 530–541 Identifying HIV infection in diagnostic histopathology tissue samples – the role of HIV‐1 p24 immunohistochemistry in identifying clinically unsuspected HIV infection: a 3‐year analysis Aims:  Because of the clinical difficulty in identifying the early stages of human immunodeficiency virus (HIV) infection, the histopathologist often has to consider the diagnosis of HIV in tissue samples from patients with no previous suspicion of HIV infection. The aim was to investigate the practicality and utility of routine HIV‐1 p24 immunohistochemistry on tissue samples received at a London histopathology laboratory.Methods and results:  Over a 3‐year period, HIV‐1 p24 was evaluated immunohistochemically on 123 cases. Of these, 37 (30%) showed positive expression of p24 in lesional follicular dendritic cells (FDCs). Of these 37 cases, 11 were not clinically suspected to be HIV+ and had no prior serological evidence of HIV infection. These cases represented lymph node biopsies, tonsillar and nasopharyngeal biopsies and a parotid excision. In addition to expression on FDCs, in 22 cases (60%), p24 also highlighted mononuclear cells and macrophages. p24 was also useful in confirming the presence of HIV in lymphoid tissue in non‐lymphoid organs such as the lung, anus, salivary gland and brain. Immunonegativity occurred in occasional known HIV+ cases, probably related to treatment or tissue processing.Conclusions:  This study confirms the usefulness of this technique in detecting unsuspected HIV infection in lymphoid and non‐lymphoid organs on histopathological material and should be part of routine evaluation of lymph nodes and lymphoid tissue in other organs if morphological or clinical features suggest HIV infection.
Innate profiles of cytokines implicated on oral tolerance correlate with low‐ or high‐suppression of humoral response
Authors: Silva Maria F. , Kamphorst Alice O. , Hayashi Elize A. , Bellio Maria , Carvalho Claudia R. , Faria Ana M. C. , Sabino Kátia C. C. , Coelho Marsen G. P. , Nobrega Alberto , Tavares Daniel , Silva Antonio C. 
Published: March 2010

SummaryOral tolerance (OT) is being studied with great interest because of its therapeutic potential in allergy and autoimmunity. In the present study, two mouse strains with extreme phenotypes of OT susceptibility (TS) or resistance (TR) to ovalbumin (OVA) were used to demonstrate whether the tr and ts genes, cumulated during 18 generations of bi‐directional genetic selection, influence expression of immunobiological traits in naive or antigen‐gavaged TR/TS mice. The difference in anti‐OVA titres was 2048‐fold between OVA‐gavaged TS and TR mice. Tolerance susceptibility to OVA gavage in individuals from a (TS × TR)F2 population was 24% high‐susceptibility, 62% low‐susceptibility and 14% non‐tolerant. Different antigens, unrelated to OVA, were tested by gavage and TS mice were generally susceptible while TR mice were resistant. The stability of TS and TR phenotypes was not affected by the use of strict protocols of intraperitoneal immunization or feeding over 30 consecutive days. The levels of interleukin‐2 (IL‐2), IL‐4, interferon‐γ and IL‐10 cytokines evaluated in concanavalin A‐stimulated spleen cells from naive mice and in OVA‐stimulated spleen cells from OVA‐gavaged mice were higher in TS mice. Interleukin‐10 was up‐regulated in OVA‐gavaged TS mice and down‐regulated in TR mice. In naive mice, the percentage of CD4+ CD25+ and CD4+ Foxp3+ spleen cells and IL‐10 expression by CD4+ cells was significantly higher in TS mice. These results indicate that regulation of IL‐10 expression could be an important factor contributing to the mechanisms controlling OT susceptibility, and that the OT responses of TR and TS individuals strongly correlate with their innate potential to secrete this cytokine.
Chimeric vaccine composed of viral peptide and mammalian heat‐shock protein 60 peptide protects against West Nile virus challenge
Authors: Gershoni‐Yahalom Orly , Landes Shimon , Kleiman‐Shoval Smadar , Ben‐Nathan David , Kam Michal , Lachmi Bat‐El , Khinich Yevgeny , Simanov Michael , Samina Itzhak , Eitan Anat , Cohen Irun R. , Rager‐Zisman Bracha , Porgador Angel 
Published: March 2010

SummaryThe protective efficacy and immunogenicity of a chimeric peptide against West Nile virus (WNV) was evaluated. This virus is the aetiological agent of West Nile fever, which has recently emerged in the western hemisphere. The rapid spread of WNV throughout North America, as well as the constantly changing epidemiology and transmission of the virus by blood transfusion and transplantation, have raised major public‐health concerns. Currently, there are no effective treatments for WNV or vaccine for human use. We previously identified a novel, continuous B‐cell epitope from domain III of the WNV envelope protein, termed Ep15. To test whether this epitope can protect against WNV infection, we synthesized a linear chimeric peptide composed of Ep15 and the heat‐shock protein 60 peptide, p458. The p458 peptide is an effective carrier peptide for subunit vaccines against other infectious agents. We now report that mice immunized with the chimeric peptide, p458‐Ep15, were resistant to lethal challenges with three different WNV strains. Moreover, their brains were free of viral genome and infectious virus. Mice immunized with Ep15 alone or with p431‐Ep15, a control conjugate, were not protected. The chimeric p458‐Ep15 peptide induced WNV‐specific immunoglobulin G antibodies that neutralized the virus and induced the secretion of interferon‐γin vitro. Challenge of chimeric peptide‐immunized mice considerably enhanced WNV‐specific neutralizing antibodies. We conclude that this chimeric peptide can be used for formulation of a human vaccine against WNV.
Memory CD4 T cells: generation, reactivation and re‐assignment
Authors: MacLeod Megan K.L. , Kappler John W. , Marrack Philippa 
Published: March 2010

SummaryImmunological memory is one of the features that define the adaptive immune response: by generating specific memory cells after infection or vaccination, the host provides itself with a set of cells and molecules that can prevent future infections and disease. Despite the obvious importance of memory cells, memory CD4 T cells are incompletely understood. Here we discuss recent progress in understanding which activated T cells surmount the barrier to enter into the memory pool and, once generated, what signals are important for memory cell survival. There is still, however, little understanding of how (or even whether) memory CD4 T cells are useful once they have been created; a surprising thought considering the critical role CD4 T cells play in all adaptive primary immune responses. In light of this, we will discuss how CD4 T memory T cells respond to reactivation in vivo and whether they are malleable to a re‐assignment of their effector response.
Identification of older hospitalised patients at risk for functional decline, a study to compare the predictive values of three screening instruments
Authors: Hoogerduijn Jita G , Schuurmans Marieke J , Korevaar Johanna C , Buurman Bianca M , De Rooij Sophia E 
Published: March 2010

Aims and objectives.  To establish a screening instrument for identifying older hospitalised patients at risk for functional decline by comparing the predictive values of three screening instruments: identification of seniors at risk, care complexity prediction instrument and hospital admission risk profile.Background.  After being hospitalised, 30–60% of older patients experience a decline in functioning, resulting in a decreased quality of life and autonomy.Design.  A prospective cohort study.Methods.  Included were patients, aged 65 years and older, acutely admitted to a general internal ward of a university teaching hospital. Within 48 hours after hospital admission, baseline data were completed – demographic, cognitive, social and pre‐admission functional status and the screening instruments. Three months after discharge, functional status was measured by telephone interview. The Katz index was used to measure functional status (six activities). Functional decline was defined as a decline of at least one point on the Katz index at three months after discharge compared to pre‐admission state.Results.  Included were 177 patients; mean age was 77·6 years and 51·7 % were male. Functional decline was found in 27·8% of all patients. Sensitivity, specificity and area under receiver operating curve for identification of seniors at risk (ISAR) were 93, 39% and 0·67, respectively. The corresponding results for the care complexity prediction instrument (COMPRI) were 70, 62% and 0·69 and for the hospital admission risk profile (HARP) 21, 89% and 0·56.Conclusion.  The discriminative values of both identification of seniors at risk and care complexity prediction instrument are fair. Hospital admission risk profile shows the poorest results. Identification of seniors at risk shows the best ability to predict those patients at risk for functional decline and seems to be the easiest instrument in clinical practice.Relevance to clinical practice.  Identifying patients at risk for functional decline is a first step in prevention, followed by geriatric assessment and targeted interventions. Studying the validity of existing instruments is necessary before implementation in clinical practice.
After axillary surgery for breast cancer – is it safe to take blood samples or give intravenous infusions?
Authors: Winge Charlotte , Mattiasson Anne‐Cathrine , Schultz Inkeri 
Published: March 2010

Aim.  To investigate the occurrence of complications after a needle puncture or intravenous injection in the ipsilateral arm of women who have undergone axillary lymph node clearance for breast cancer.Background.  After axillary lymph node clearance in patients with breast cancer, some women experience lymphoedema and recurrent infections. To reduce the risk of these postoperative complications, most women are advised to not have intravenous infusions in, or blood samples taken from, the arm in the operated side. Very little published data are available regarding the incidence of lymphoedema after intravenous procedures under clean conditions in the hospital setting. This study set out to investigate the occurrence of complications after a needle puncture or intravenous injection in the ipsilateral arm of women who have undergone axillary lymph node clearance for breast cancer is therefore important.Design.  Descriptive.Methods.  Self‐reported questionnaire.Results.  Most of the reported complications were minor, including itching, bruises and vomiting at the time of the intravenous procedure. The most serious complication was infection in one patient needing antibiotic treatment and subsequent arm swelling.Conclusions.  This study indicates that if a blood sample is taken or intravenous injection is given according to the current Swedish guidelines for health care professionals, there should be a very low risk of complications.Relevance to clinical practice.  If intravenous procedures are performed without any disadvantage in the arm of the operated side in women who have undergone axillary surgery, the clinical problem of finding a proper vein and the psychological concern of the women can be reduced.
Safety profiles of second‐line tyrosine kinase inhibitors in patients with chronic myeloid leukaemia
Authors: Tinsley Sara M 
Published: March 2010

Aims and objectives.  To review the use of second‐line tyrosine kinase inhibitors in patients with chronic myeloid leukaemia (CML) and provide recommendations for managing adverse events (AEs) to maximise patient benefit.Background.  Treatment of CML has been revolutionised with the advent of tyrosine kinase inhibitors (TKIs) that target the breakpoint cluster region‐Abelson (BCR‐ABL) kinase. Imatinib is the only first‐line TKI currently available for the treatment of CML; however, intolerance and resistance remain significant clinical challenges. The approved second‐line treatment options for CML are dasatinib, nilotinib or escalated‐dose imatinib.Design.  Review article.Methods.  Searches of PubMed, ASCO and ASH electronic databases for relevant search terms were performed between July 2008–January 2009.Findings.  Dasatinib has no cross‐intolerance with imatinib, and the most frequent AEs (cytopenias and pleural and pericardial effusions) can generally be managed by dose interruption and reduction. Nilotinib has a high degree of haematologic cross‐intolerance with first‐line imatinib. As might be expected, high‐dose imatinib has the potential for more severe AEs than standard‐dose imatinib.Conclusions.  There are known safety issues inherent to each TKI and close monitoring by nursing staff is necessary to identify and effectively manage AEs.Relevance to clinical practice.  All three TKIs have demonstrated potential for fluid retention and cardiotoxicity. Nurses should be aware of how these AEs manifest and intervene appropriately. The safety profiles of these TKIs clearly differs and it is important to consider factors such as comorbidities when making treatment decisions.