bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality control in diagnostic molecular pathology in the Netherlands; proficiency testing for patient identification in tissue samples
Authors: Thunnissen F B J M , Tilanus M G J , Ligtenberg M J L , Nederlof P M , Dinjens W N M , Meulemans E , Van den Brule A J C , van Noesel C J M , de Leeuw W J F , Schuuring E 
Published: June 2004

Aims:To describe the evolution of proficiency testing for molecular diagnostic pathology with respect to determining unambiguously the patient identity of tissue samples by microsatellite analysis.Method:Four rounds of quality control exchanges of samples from different patients were sent with the purpose of identifying the correct origin of these samples. The samples were either paraffin wax embedded sections on glass, sections in tubes, or isolated DNA. Blinded samples were distributed to all participating laboratories. No restrictions to the method and short tandem repeat markers used for identification were imposed.Results:In four subsequent rounds the number of participating laboratories increased from three to 10. The numbers of samples tested increased in time from five to 12. The microsatellite markers used by the different laboratories showed little overlap. In the first three rounds, in which isolated DNA was provided, all samples were accurately classified irrespective of the microsatellite markers used. In the last round, which also included paraffin wax embedded sections, a small number of laboratories experienced problems, either with amplification or incorrect classification of a few samples.Conclusion:Proficiency testing was useful, and showed country wide high quality and correct identification of (patient) samples with molecular techniques for diagnostic purposes.
Plasma glucose measurement with the Yellow Springs Glucose 2300 STAT and the Olympus AU640
Authors: Twomey P J 
Published: June 2004

Background:Diabetes mellitus is an important diagnosis. New criteria have been defined for impaired glucose metabolism and, accordingly, there is a need for precise and accurate glucose analysis for the correct classification of patients. However, neither the World Health Organisation nor the National Service Framework for Diabetes in England and Wales deal with the associated analytical issues for plasma glucose.Aims/Methods:To compare two different methods for plasma glucose with respect to European and CLIA ’88 quality requirements.Results:Using several different graphical and statistical techniques, the YSI 2300 STAT was found to be 8.1–8.4% negatively biased for plasma glucose when compared with the Olympus AU640 method.Conclusions:Such a large bias would have a large impact on the detection of diabetes mellitus in clinical practice and therefore this method should not be used to make a definitive diagnosis. The bias probably results from the fact that the YSI 2300 STAT uses an aqueous based standard.
Lack of lymphangiogenesis during breast carcinogenesis
Authors: Vleugel M M , Bos R , van der Groep P , Greijer A E , Shvarts A , Stel H V , van der Wall E , van Diest P J 
Published: June 2004

Background:Recent evidence suggests that functional intratumorous lymph vessels may be absent from some human cancers. This could result from either the failure of tumours to induce lymphangiogenesis, or the collapse of lymph vessels, caused by high interstitial tumour pressure.Methods:To differentiate between these two hypotheses, paraffin wax embedded clinical specimens from normal breast (n  =  13), usual ductal hyperplasia (n  =  11), ductal carcinoma in situ (n  =  21), and invasive breast cancer (n  =  40) were compared for lymphatic and blood vessel density by immunohistochemistry with antibodies to the lymphatic endothelial hyaluronan receptor (LYVE-1) and CD31, respectively.Results:Lymph vessel density was lower than blood vessel density in normal breast tissue. Within breast lobuli, lymph vessels were absent. In premalignant lesions blood microvessel density increased, whereas no increase in lymph vessels could be seen intralesionally. In invasive cancers, lymph vessels were absent in all but a few cases, where probably some pre-existing lymph vessels remained, although blood microvessel density was once again increased.Conclusion:Unlike angiogenesis, lymphangiogenesis is absent during breast carcinogenesis. This, and not rising interstitial pressure caused by an increase in the size of lesions, explains the absence of intratumorous lymph vessels in invasive breast cancer.
Versican expression in pharyngeal squamous cell carcinoma: an immunohistochemical study
Authors: Pukkila M J , Kosunen A S T , Virtaniemi J A , Kumpulainen E J , Johansson R T , Kellokoski J K , Nuutinen J , Kosma V-M 
Published: June 2004

Aims:To study the expression of versican, a large proteoglycan involved in repressing adhesion between cells and the extracellular matrix in pharyngeal squamous cell carcinoma (PSCC), and its relation to the expression of p53 and catenins, histological differentiation, clinical data, and prognosis.Methods:For the retrospective survey, primary tumours for analyses were obtained from 118 patients diagnosed with PSCC of the oropharynx or hypopharynx. The immunohistochemical expression of versican was studied and was related to the expression pattern of p53 and catenins, in addition to clinical data and survival.Results:In the primary tumours, strong stromal versican expression was graded as low in 59 (50%) and high in 59 (50%) cases. In addition, intracellular versican staining was seen in nine (8%) tumours. In local lymph node metastases, strong stromal versican staining was significantly more frequent compared with the primary tumours (p  =  0.018). Strong stromal versican staining was more frequently seen in less advanced tumours (p  =  0.015). There was no association between versican expression and the other investigated variables (p53, catenins, TNM status, and histological grade). Neither stromal nor intracellular versican expression predicted overall survival in these patients.Conclusions:Versican was more strongly expressed in the stroma of local metastases and in the earlier stages of disease in PSCC. However, versican expression was not an independent prognostic factor in this entity.
Technical variations in prostatic immunohistochemistry: need for standardisation and stringent quality assurance in PSA and PSAP immunostaining
Authors: Varma M , Berney D M , Jasani B , Rhodes A 
Published: June 2004

Aims:To assess variations in prostate specific antigen (PSA) and prostate specific acid phosphatase (PSAP) immunohistochemistry with particular reference to the antibody type (monoclonal or polyclonal) and the tissues used for optimising immunostaining conditions and as external positive controls.Methods:A questionnaire was sent to all laboratories registered with the UK National External Quality Assurance Scheme for immunohistochemistry enquiring about the immunohistochemical methods routinely used for the diagnosis of prostate cancer.Results:Responses were received from 220 (68%) laboratories. All UK respondents routinely performed PSA immunostaining but PSAP immunostaining was available in only 57% of these laboratories. Monoclonal anti-PSA, polyclonal anti-PSA, monoclonal anti-PSAP, and polyclonal anti-PSAP were used by 40%, 60%, 29%, and 27% of UK respondents, respectively. Benign prostate tissue was most commonly used to determine optimal antibody dilutions and as external quality control for PSA/PSAP, with only 6% and 3% of respondents, respectively, including high grade prostate cancer in the tissues used for these purposes.Conclusions:The wide variation in the methods used highlights the need for standardisation and more stringent quality assurance of the immunohistochemical staining techniques used for PSA and PSAP. The widespread use of benign prostate tissue to determine optimal antibody dilutions and as an external positive control for PSA and PSAP immunostaining is of particular concern because this approach may result in a method that is not sufficiently sensitive to detect the reduced PSA and PSAP expression associated with high grade prostate cancer.
Are heterogenous results of EGFR immunoreactivity in renal cell carcinoma related to non-standardised criteria for staining evaluation?
Authors: Langner C , Ratschek M , Rehak P , Schips L , Zigeuner R 
Published: June 2004

Aims:To assess whether heterogeneity of epidermal growth factor receptor (EGFR) immunoreactivity in renal cell carcinoma (RCC) is related to non-standardised criteria for staining evaluation.Methods:EGFR expression was investigated in 132 primary and 55 metastatic conventional RCCs using a tissue microarray technique.Results:Overall, membranous and/or cytoplasmic EGFR immunostaining was present in 123 of 132 (93%) primary and 49 of 53 (92%) metastatic RCCs, with extensive immunoreactivity (> 50% of tumour cells) in 110 of 132 (83%) primary tumours and 39 of 53 (73%) metastases. Cytoplasmic staining was associated with high tumour stage and high tumour grade. In addition, strong membranous staining (score 3+) prevailed in high grade RCCs. Cytoplasmic immunostaining was associated with an unfavourable prognosis, whereas overall (cytoplasmic and membranous) immunoreactivity and intensity of membranous staining were not.Conclusions:Different methods of immunohistochemical evaluation led to different results, strengthening the need for standardisation, especially against a background of rapidly evolving EGFR targeted cancer treatment strategies.
The value of an elastic tissue stain in detecting venous invasion in colorectal cancer
Authors: Vass D G , Ainsworth R , Anderson J H , Murray D , Foulis A K 
Published: June 2004

Background:Venous invasion by tumour is an independent prognostic indicator of both prognosis and risk of development of distant metastases in colorectal carcinoma. The use of special stains to aid its detection in pathology specimens is not currently universally recommended.Aims:To determine whether an elastica stain significantly increases the incidence of detection of vascular invasion compared with routinely stained sections.Methods:Serial sections from the 75 cases of colorectal carcinoma were stained by haematoxylin and eosin (H&E) only and elastica counterstained with H&E. The incidence of both intramural and extramural venous invasion was recorded and compared with that seen when the tumours were originally reported.Results:Extramural venous invasion had been noted in 14 of the pathology reports and was seen in 18 cases when only the H&E sections were viewed in the study. It was present in 32 cases when elastica stained sections were analysed. Intramural venous invasion was seen in eight cases on H&E sections and 30 cases on elastica stained sections.Conclusion:The use of elastica stained serial sections to detect venous invasion in tumours should be recommended in guidelines for the reporting of colorectal carcinomas.
High molecular weight caldesmon positive stromal cells in the capsule of hepatocellular carcinomas: Figure 1
Authors: Nakayama H , Enzan H , Yamamoto M , Miyazaki E , Yasui W 
Published: June 2004

Aims:To investigate the smooth muscle nature of the stromal cells in the capsule of hepatocellular carcinomas.Methods:Immunohistochemical analysis using monoclonal antibody to high molecular weight caldesmon (HCD), a highly specific marker for smooth muscle cells, was performed in 33 encapsulated hepatocellular carcinomas and adjacent hepatic tissues.Results:HCD positive stromal cells were detected in the capsule of 21 of the 33 hepatocellular carcinomas examined.Conclusions:The capsule of hepatocellular carcinomas contains smooth muscle cells.
COHERENT SS DEMODULATION WITH ESTIMATION AND COMPENSATION OF PHASE ROTATION USING A PILOT CHANNEL
Authors: IIJIMA YASUYUKI , INOUE SHIGEYUKI , KASHIMA TOMOKO , FUKASAWA ATSUSHI , TAKIZAWA YUMI 
Published: June 2004

This paper describes and clarifies a configuration and its performance of estimation and compensation of phase rotation in radio propagation using a pilot channel for the SS (spread spectrum) modulation and demodulation. Coherent radio transmission scheme is composed as follows: (i) Continuous pilot signal is transmitted through a pilot channel, (ii) the pilot channel is composed of O-QPSK and QPSK for reverse and forward links, respectively, (iii) pilot signal is added in each I channel of O-QPSK and QPSK, and (iv) coherent demodulation is achieved by estimation and compensation of phase rotation using the pilot channel. Phase rotation and its linearity has been estimated for QPSK and O-QPSK data modulation methods. The constellation on the complex plane is used for the evaluation of phase rotation and the Eye pattern for the demodulated waveforms. The bit-error-rate (BER) versus Eb/N0 is used for the characteristics of data modulation/demodulation and SS modulation/demodulation of the proposed radio system. A proposed scheme proved that (i) estimation of rapid phase rotation caused by multipath radio propagation with high-speed Doppler shift in frequency is well realized by the use of continuous pilot transmission (pilot channel), (ii) compensation of rapid phase rotation is well done by simplified logic operations, and (iii) high performance for high speed data transmission is realized by coherent demodulation. This system will be applied to wireless LANs with high performances and simplified configurations.
Targeting the multidrug resistance-1 transporter in AML: molecular regulation and therapeutic strategies
Authors: Mahadevan Daruka , List Alan F. 
Published: June 2004

AbstractThe multidrug resistance-1 (MDR1) gene product, P-glycoprotein (P-gp), and the multidrug resistance–related proteins (MRPs) are members of the adenosine triphosphate (ATP)–binding cassette (ABC) transporter gene superfamily that regulates the trafficking of drugs, peptides, ions, and xenobiotics across cell membrane barriers. Three-dimensional modeling of human MDR1/P-gp indicates that these glycoproteins function as efficient, ATP-dependent gate-keepers, which scan the plasma membrane and its inner leaflet to flip lipophilic substrates to the outer membrane leaflet. Delineation of the adverse prognostic power of MDR1 in adult acute myeloid leukemia (AML) raised hopes that pharmacologic blockade of P-gp would improve the outcome of conventional cytotoxic therapy, perhaps more so than in any other human malignancy. Phase 3 clinical trials investigating first- and second-generation P-gp antagonists have yielded conflicting results, emphasizing the importance of applying preclinical principals to realistically appraise expectations for clinical benefit. Structure-based design strategies and the delineation of transcriptional regulators of survival gene cassettes promise to yield novel, more-effective strategies to overcome drug resistance. Lessons learned from investigations of these and other mechanisms of cellular defense hold promise for a renaissance in the development of targeted therapeutics in acute leukemia.
Novel hemophilia B mouse models exhibiting a range of mutations in the Factor IX gene
Authors: Sabatino Denise E. , Armstrong Elina , Edmonson Shyrie , Liu Yi-Lin , Pleimes Marc , Schuettrumpf Joerg , Fitzgerald Julie , Herzog Roland W. , Arruda Valder R. , High Katherine A. 
Published: June 2004

AbstractAnimal models have been critical to the development of novel therapeutics in hemophilia. A deficiency of current murine models of hemophilia B is that they are all due to gene deletions, a type of mutation that is relatively rare in the human hemophilia population. We generated mice with a range of mutations in the Factor IX (F.IX) gene; these more faithfully reflect the types of mutations that cause disease in the human population. Transgenic mice expressing either wild-type human F.IX (hF.IX), or F.IX variants with premature translation termination codons, or missense mutations, under the control of the murine transthyretin promoter, were generated and crossed with mice carrying a large deletion of the murine F.IX gene. Gene copy number, F.IX transcript levels in the liver, intrahepatocyte protein expression, and circulating levels of F.IX protein in the mice were determined and compared with data generated by transient transfection assays using the same F.IX variants. Mice were injected with a viral vector expressing hF.IX and displayed a range of immune responses to the transgene product, depending on the underlying mutation. These new mouse models faithfully mimic the mutations causing human disease, and will prove useful for testing novel therapies for hemophilia. (Blood. 2004;104:2767-2774)
P-selectin binding to P-selectin glycoprotein ligand-1 induces an intermediate state of αMβ2 activation and acts cooperatively with extracellular stimuli to support maximal adhesion of human neutrophils
Authors: Ma Yan-Qing , Plow Edward F. , Geng Jian-Guo 
Published: June 2004

AbstractP-selectin glycoprotein ligand 1 (PSGL-1, CD162) and integrin αMβ2 (Mac-1, CD11bCD18) are leukocyte adhesion molecules essential for innate immunity and inflammation. The interaction of PSGL-1 with P-selectin (CD62P) mediates tethering, rolling, and weak adhesion of leukocytes, during which they become sufficiently activated in situ by locally released or displayed cytokines and chemoattractants for integrin-mediated firm adhesion. However, communication between P-selectin and the integrin, whether P-selectin can trigger β2-integrin activation, remains controversial. We found that P-selectin immunoglobulin chimera and PSGL-1 monoclonal antibodies (mAbs) increased adhesion of human neutrophils to immobilized, but not soluble, fibrinogen. This intermediate state of neutrophil adhesion was defined by moderate clustering of integrin αMβ2, no increase in CBRM1/5 (a mAb specific for the activation epitope on the αM subunit) recognition, and no increase in surface expression of αMβ2, whereas phorbol myristate acetate (PMA) induced extensive changes in these 3 parameters. Furthermore, platelet-activating factor or interleukin 8 acted in concert with P-selectin for further enhancing the activation of αMβ2. We thus propose a model in which P-selectin induces an intermediate state of integrin activation and then cooperates with other extracellular stimuli to support maximal adhesion of human neutrophils.
Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications
Authors: Kojouri Kiarash , Vesely Sara K. , Terrell Deirdra R. , George James N. 
Published: June 2004

AbstractSplenectomy has been a standard treatment for adult patients with idiopathic thrombocytopenic purpura (ITP) for more than 50 years. However, the durability of responses, the ability to predict who will respond, and the frequency of surgical complications with splenectomy all remain uncertain. To better interpret current knowledge we systematically identified and reviewed all 135 case series, 1966 to 2004, that described 15 or more consecutive patients who had splenectomy for ITP and that had data for 1 of these 3 outcomes. Complete response was defined as a normal platelet count following splenectomy and for the duration of follow-up with no additional treatment. Forty-seven case series reported complete response in 1731 (66%) of 2623 adult patients with follow-up for 1 to 153 months; complete response rates did not correlate with duration of follow-up (r = -0.103, P = .49). None of 12 preoperative characteristics that have been reported consistently predicted response to splenectomy. Mortality was 1.0% (48 of 4955 patients) with laparotomy and 0.2% (3 of 1301 patients) with laparoscopy. Complication rates were 12.9% (318 of 2465) with laparotomy and 9.6% (88 of 921 patients) with laparoscopic splenectomy. Although the risk of surgery is an important consideration, splenectomy provides a high frequency of durable responses for adult patients with ITP. (Blood. 2004; 104:2623-2634)
VEGF induces Mcl-1 up-regulation and protects multiple myeloma cells against apoptosis
Authors: Le Gouill Steven , Podar Klaus , Amiot Martine , Hideshima Teru , Chauhan Dharminder , Ishitsuka Kenji , Kumar Shaji , Raje Noopur , Richardson Paul G. , Harousseau Jean-Luc , Anderson Kenneth C. 
Published: June 2004

AbstractInterleukin-6 (IL-6) triggers multiple myeloma (MM) cell proliferation and protects against apoptosis by up-regulating myeloid cell leukemia 1 (Mcl-1). Vascular endothelial growth factor (VEGF) induces modest proliferation of MM cells and induces IL-6 secretion in a paracrine loop involving MM cells and bone marrow stromal cells. Using murine embryonic fibroblast cell lines as a model (Mcl-1wt/wt and Mcl-1Δ/null MEFs), we here demonstrate that deletion of Mcl-1 reduces fetal bovine serum (FBS)-, VEGF-, and IL-6-induced proliferation. We also show that VEGF up-regulates Mcl-1 expression in a time- and dose-dependent manner in 3 human MM cell lines and MM patient cells. Importantly, we demonstrate that the pan-VEGF inhibitor, GW654652, inhibits VEGF-induced up-regulation of Mcl-1 and, as with Mcl-1 siRNA, is associated with decreased proliferation and induction of apoptosis. Finally, we show that VEGF protects MM patient cells against FBS starvation-induced apoptosis. Our studies therefore demonstrate that VEGF-induced MM cell proliferation and survival are mediated via Mcl-1, providing the preclinical framework for novel therapeutics targeting Mcl-1 and/or VEGF to improve patient outcome in MM.
Impact of modifications of heterocyclic bases in CpG dinucleotides on their immune-modulatory activity
Authors: Vollmer Jörg , Weeratna Risini D , Jurk Marion , Davis Heather L , Schetter Christian , Wüllner Meike , Wader Tanja , Liu Ming , Kritzler Andrea , Krieg Arthur M 
Published: June 2004

AbstractSynthetic phosphorothioate oligodeoxynucleotides (ODN) bearing unmethylated CpG motifs can mimic the immune-stimulatory effects of bacterial DNA and are recognized by Toll-like receptor 9 (TLR9). Past studies have demonstrated that nucleotide modifications at positions at or near the CpG dinucleotides can severely affect immune modulation. However, the effect of nucleotide modifications to stimulate human leukocytes and the mechanism by which chemically modified CpG ODN induce this stimulation are not well understood. We investigated the effects of CpG deoxyguanosine substitutions on the signaling mediated by human TLR9 transfected into nonresponsive cells. ODN incorporating most of these substitutions stimulated detectable TLR9-dependent signaling, but this was markedly weaker than that induced by an unmodified CpG ODN. One of the most active ODN tested contained deoxyinosine for deoxyguanosine substitutions (CpI ODN), but its relative activity to induce cytokine secretion on mouse cells was much weaker than on human cells. The activity was dependent on TLR9, as splenocytes from mice genetically deficient in TLR9 did not respond to CpI ODN stimulation. It is surprising that CpI ODN were nearly as strong as CpG ODN for induction of human B cell stimulation but were inferior to CpG ODN in their ability to induce T helper cell type 1 effects. These data indicate that certain deoxyguanosine substitutions in CpG dinucleotides are tolerated to stimulate a TLR9-mediated immune response, but this response is insufficient to induce optimal interferon-α-mediated effects, which depend on the presence of an unmodified CpG dinucleotide. These studies provide a structure-activity relationship for TLR9 agonist compounds with diverse immune effects.