bluuebunny/crossref_metadata_2025_split huggingface dataset:
Search for a Prion-Specific Nucleic Acid
Authors: Safar Jiri G. , Kellings Klaus , Serban Ana , Groth Darlene , Cleaver James E. , Prusiner Stanley B. , Riesner Detlev 
Published: July 2005

ABSTRACT

Diversity of prion strains was attributed to an elusive nucleic acid, yet a search spanning nearly two decades has failed to identify a prion-specific polynucleotide. In our search for a prion-specific nucleic acid, we analyzed nucleic acids in purified fractions from the brains of Syrian hamsters infected with Sc237 prions. Purification of Sc237 prions removed nucleic acids larger than 50 nucleotides as measured by return refocusing electrophoresis (RRGE). To determine the size of the largest polynucleotide present in purified fractions at an abundance of one molecule per infectious (ID
50
) unit, we measured prions present after inoculation. In order to account for the rapid clearance of prions after intracerebral inoculation, we determined the number of PrP
Sc
molecules and ID
50
units of prions that were retained in brain. Factoring in clearance after inoculation, we estimate that the largest polynucleotide present in our purified fractions at one molecule per ID
50
unit is ≈25 nucleotides in length. In the same fractions, there were ≈3,000 protease-resistant PrP
Sc
molecules per ID
50
unit after accounting for clearance of PrP
Sc
following inoculation. We compared the resistance of Sc237 and 139H prions to inactivation by UV irradiation at 254 nm. Irradiation of homogenates and microsomes diminished prion infectivity by a factor of ≈1,000 but did not alter the strain-specified properties of the Sc237 and 139H prions. The data reported here combined with the production of synthetic prions argue that the 25-mer polynucleotides found in purified prion preparations are likely to be host encoded and of variable sequence; additionally, these 25-mers are unlikely to be prion specific.
Studies of H5N1 Influenza Virus Infection of Pigs by Using Viruses Isolated in Vietnam and Thailand in 2004
Authors: Choi Young Ki , Nguyen Tien Dzung , Ozaki Hiroichi , Webby Richard J. , Puthavathana Pilaipan , Buranathal Chantanee , Chaisingh Arunee , Auewarakul Prasert , Hanh N. T. H. , Ma Sia Kit , Hui Pui Yan , Guan Yi , Peiris Joseph Sriyal Malik , Webster Robert G. 
Published: July 2005

ABSTRACT
To determine whether avian H5N1 influenza viruses associated with human infections in Vietnam had transmitted to pigs, we investigated serologic evidence of exposure to H5N1 influenza virus in Vietnamese pigs in 2004. Of the 3,175 pig sera tested, 8 (0.25%) were positive for avian H5N1 influenza viruses isolated in 2004 by virus neutralization assay and Western blot analysis. Experimental studies of replication and transmissibility of the 2004 Asian H5N1 viruses in pigs revealed that all viruses tested replicated in the swine respiratory tract but none were transmitted to contact pigs. Virus titers from nasal swabs peaked on day 2, and low titers were detected in the liver of two of the four pigs tested. Our findings indicate that pigs can be infected with highly lethal Asian H5N1 viruses but that these viruses are not readily transmitted between pigs under experimental conditions.
Expression of apoptosis related proteins during malignant progression in chronic ulcerative colitis
Authors: van der Woude C J , Moshage H , Homan M , Kleibeuker J H , Jansen P L M , van Dekken H 
Published: July 2005

Background:Chronic ulcerative colitis (CUC) is associated with increased risk of developing colon cancer through a dysplasia (intraepithelial neoplasia)–carcinoma sequence.Aims:To investigate the expression of apoptosis and inflammatory related proteins in CUC.Methods:The expression of proteins involved in apoptosis and inflammation (inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), Bcl-xl, Fas, and active caspase 3) was investigated and compared with that seen in sporadic colon carcinoma.Results:COX-2 was negative in the epithelium of all samples. iNOS was clearly present in inflammatory areas in CUC epithelium, weakly expressed in dysplasia, and absent or weakly expressed in tumour cells. Bcl-xl was absent in CUC, increased in dysplasia, and highly expressed in most carcinomas. Fas expression was positive in the surface epithelium of CUC, dysplasia, and most tumour cells. Activated caspase 3 was weakly positive in all samples, indicating limited apoptosis. Compared with CUC associated carcinoma, iNOS was consistently expressed in sporadic colon carcinoma cells, whereas Bcl-xl was almost absent in these tumour cells and Fas was only weakly expressed. Activated caspase 3 was present in normal mucosal samples and some tumour cells.Conclusion:Apoptosis related proteins—particularly iNOS, Bcl-xl, and Fas—show a distinct pattern of expression in the CUC to carcinoma sequence, which differs from that seen in sporadic carcinoma, but bears a striking resemblance to that seen during neoplastic progression in Barrett’s oesophagus. These results support a causal role for chronic inflammation in cancer development in CUC, and treatment of ulcerative colitis should aim to minimise inflammation.
Change of pathology request forms can reduce unwanted requests and tests
Authors: Bailey J , Jennings A , Parapia L 
Published: July 2005

Background:Developments in clinical and laboratory medical practice have resulted in a large increase in laboratory workload, with considerable financial implications. It has been shown that the design of laboratory request cards can influence patterns of test ordering and possibly reduce inappropriate requests.Aims/Methods:To redesign pathology request cards with a view to reducing inappropriate test requesting.Results:A redesign of the request cards used by general practitioners in the Bradford area led to a significant reduction in the ordering of specific investigations.Conclusions:The redesigning of pathology request cards can have a beneficial effect on test requesting.
MUC4 expression is a novel prognostic factor in patients with invasive ductal carcinoma of the pancreas
Authors: Saitou M , Goto M , Horinouchi M , Tamada S , Nagata K , Hamada T , Osako M , Takao S , Batra S K , Aikou T , Imai K , Yonezawa S 
Published: July 2005

Background:Many patients with invasive ductal carcinoma of the pancreas (IDC) have a poor outcome. MUC4 expression has been implicated as a marker for diagnosis and progression of IDC, but there are no studies of the relation between MUC4 expression and patient prognosis in IDC.Aims:To investigate the prognostic significance of MUC4 expression in IDC.Methods:The expression profiles of MUC4, ErbB2, p27, and MUC1 were investigated in IDC tissues from 135 patients by means of immunohistochemistry.Results:MUC4 was expressed in 43 of the 135 patients with IDC (31.9%). The survival of 21 patients with high MUC4 expression (>20% of neoplastic cells stained) was significantly worse than that of the 114 patients with low MUC4 expression (<20% of neoplastic cells stained) (p  =  0.0043). Univariate analysis showed that high MUC4 expression (p  =  0.0061), large primary tumour status (>T2) (p  =  0.0436), distant metastasis (p  =  0.0383), lymphatic invasion (p  =  0.0243), and surgical margins (p  =  0.0333) were significant risk factors affecting the outcome of patients with IDC. Backward stepwise multivariate analysis showed that MUC4 expression (p  =  0.0121), lymph node metastasis (p  =  0.0245), and lymphatic invasion (p  =  0.0239) were significant independent risk factors. ErbB2, p27, and MUC1 were not independent risk factors.Conclusions:This study shows that MUC4 expression in IDC is a new independent factor for poor prognosis and predicts the outcome of patients with IDC.
Patients’ perspective of pathology specimens. A prospective study
Authors: Hock Y L , Balachandar C , Dicken S , Bayley C , Ramaiah S 
Published: July 2005

Aim:To determine the degree of patients’ interest in surgical pathology specimens. To assess the impact of patients’ involvement in surgical pathology on their understanding of (and confidence in) the storage and use of pathology specimens.Methods:Forty seven patients were invited to visit the pathology department and view their specimens postoperatively. Those who visited were asked to complete a questionnaire to assess the effect of the visit.Results:Thirty three of the 47 patients wished to view their specimens, but only 14 actually made the visit. All those who visited indicated that it made them better able to understand the reason for surgery and tissue retention issues, and more likely to consent to the use of excess tissue for research.Conclusion:In general, patients are keen to know what happens to and what is wrong with the organs removed at surgery, and their involvement in surgical pathology can have positive and beneficial effects both for themselves and the profession.
Granulomatous reactions cause symptoms or clinically imitate treatment resistance in small lymphocytic lymphoma/chronic lymphocytic leukaemia more frequently than in other non-Hodgkin lymphomas
Authors: Brunner A , Kantner J , Tzankov A 
Published: July 2005

Aims:The electronic database of the institute of pathology, Medical University of Innsbruck, was reviewed and patient histories studied to analyse systematically the coincidence of granulomatous reactions and lymphomas in a large patient collective, and to find distinct clinicopathological correlations. Five cases of small lymphocytic lymphoma/chronic lymphocytic leukaemia (CLL) associated with granulomatous reactions in lymph nodes and bone marrow were identified, all clinically associated with signs of progressive disease.Methods:Cases were acquired by reviewing an electronic database comprising approximately 715 000 patients diagnosed between 1993 and 2003. Histochemical, immunohistochemical, and molecular techniques were used to verify diagnosis and associated infectious diseases. Clinical data were obtained from reviewing the charts.Results:Of 2044 bone marrow and 411 lymph node non-Hodgkin lymphoma biopsy samples, CLL was most frequently associated with bone marrow (two cases) and lymph node granulomas (three cases). These granulomas were mostly composed of epithelioid cells, with or without giant cells, and in all but one case did not show necrosis. All patients with CLL had clinical symptoms primarily caused by the granulomatous disease: two suffered from acid fast bacilli infections (Mycobacterium tuberculosisand mycobacteria other than tuberculosis) and three presented with clinical manifestations of sarcoidosis (the reason a diagnostic biopsy was performed).Conclusions:Granulomatous reactions in patients with CLL might obscure diagnosis and imitate disease progression and Richter’s transformation. Careful histological examination, exclusion of infectious agents, and a detailed clinical history are essential for correct diagnosis.
Comparison of liquid based cytology and histology for the evaluation of HER-2 status using immunostaining and CISH in breast carcinoma
Authors: Sartelet H , Lagonotte E , Lorenzato M , Duval I , Lechki C , Rigaud C , Cucherousset J , Durlach A , Graesslin O , Abboud P , Doco-Fenzy M , Quereux C , Costa B , Polette M , Munck J-N , Birembaut P 
Published: July 2005

Background:HER-2 amplification is an important prognostic biomarker and treatment determinant in breast carcinoma.Aims:To correlate immunocytochemical (ICC) expression of HER-2 and gene amplification determined by chromogenic in situ hybridisation (CISH) using liquid based cytology (LBC) with immunohistochemistry (IHC) and CISH using histological samples of the same breast carcinomas.Methods:Frozen sections and cytobrushings of 103 breast carcinomas were analysed. Four techniques were performed on each tumour: two on LBC samples (ICC, and CISH, both graded as positive, indeterminate, or negative) and two on histological samples (IHC and CISH). Two cell lines (MCF-7, negative; BT 474, positive) were used as controls for cytological analysis. A complementary fluorescence in situ hybridisation technique was carried out in histological samples with low amplification (4–10 dots/nucleus).Results:Interobserver agreement for the four techniques calculated by the κ coefficient indicated a substantial agreement. Nine cases failed in cytology because of poor cellularity. Among 94 cases, 19 were amplified; 73, 12, and 9 tumours were scored 0 or 1+, 2+, and 3+, respectively by IHC and 75, 13, and 6, respectively, by ICC. CISH found no amplification in 72 tumours. Correlations between the IHC and CISH results in the histological and cytological samples were always significant.Conclusions:Her-2 status could be determined in LBC samples and correlated well with reference histological methods using in situ hybridisation. ICC was less reliable because of the presence of the cytoplasmic membrane. However, these results should be confirmed by a large multicentre study.
Microsatellite instability and gastric non-invasive neoplasia in a high risk population in Cesena, Italy
Authors: Rugge M , Bersani G , Bertorelle R , Pennelli G , Russo V M , Farinati F , Bartolini D , Cassaro M , Alvisi V 
Published: July 2005

Background/Aims:In the natural history of gastric cancer, non-invasive neoplasia (NiN) precedes invasive carcinoma. A histological classification of gastric NiN has recently been proposed by a World Health Organisation international panel of experts. Genetic instability is known to be among the molecular pathways involved in gastric oncogenesis. In this retrospective cross sectional study, microsatellite instability (MSI) was analysed in a consecutive series of NiN and NiN related histological alterations from a northern Italian region at high risk for gastric cancer.Patients/Methods:Fifty five consecutive cases (indefinite for NiN, 29 cases; low grade NiN, 17 cases; high grade NiN, nine cases) were analysed by radioactive polymerase chain reaction and electrophoresis for microsatellite alterations at six loci (BAT25, BAT26, D2S123, D5S346, D17S250, and D3S1317). MSI was defined according to the Bethesda criteria distinguishing: (1) no instability in the analysed loci; (2) low frequency MSI (MSI-L); and (3) high frequency MSI (MSI-H). Immunohistochemical expression of MLH1 and MSH2 proteins was also analysed in all cases.Results:Overall, MSI was found in 11 of 55 cases (indefinite for NiN, five of 29 (MSI-L, four; MSI-H, one); low grade NiN, three of 17 (MSI-L, one; MSI-H, two); high grade NiN, three of nine (MSI-L, one; MSI-H, two).Conclusions:In an Italian high risk area for gastric cancer, MSI is part of the spectrum of genetic alterations in gastric non-invasive neoplasia. In European populations at high risk of gastric cancer, DNA repair system alterations are thought to be among the early molecular events in gastric carcinogenesis.
MAX-MIN FAIR FLOW CONTROL SENSITIVE TO PRIORITIES
Authors: FATOUROU PANAGIOTA , MAVRONICOLAS MARIOS , SPIRAKIS PAUL 
Published: July 2005

Flow control is the dominant technique currently used in communication networks for preventing excess traffic from flooding the network, and for handling congestion. In rate-based flow control, transmission rates of sessions are adjusted in an end-to-end manner through a sequence of operations. In this work, we present a theory of max-min fair, rate-based flow control sensitive to priorities of different sessions, as a significant extension of the classical theory of max-min fair, rate-based flow control to networks supporting applications with diverse requirements on network resources. Each individual session bears a priority function, which maps the session's priority to a transmission rate; the priority is a working abstraction of the session's priority to bandwidth access. Priority functions enable the specification of requirements on bandwidth access by distributed applications, and the formal handling of such requirements. We present priority max-min fairness, as a novel and well motivated fairness condition which requires that assigned rates correspond, through the priority functions, to priorities comprising a max-min vector. We also introduce priority bottleneck algorithms gradually update a session's rate until when its priority is restricted on a priority bottleneck edge of the network. We establish a collection of interesting combinatorial properties of priority bottleneck algorithms. Most significantly, we show that they can only converge to priority max-min fairness. As an application of our general theory, we embed priority bottleneck algorithms in the more realistic optimistic framework for rate-based flow control. The optimistic framework allows for both decreases and increases of session rates. We exploit these additionally provided semantics to prove further combinatorial properties for the termination of priority bottleneck algorithms in the optimistic framework. We use these properties to conclude the first optimistic algorithms for efficient, max-min fair, rate-based flow control sensitive to priorities.
Inhibiting the IGF-1 receptor tyrosine kinase with the cyclolignan PPP: an in vitro and in vivo study in the 5T33MM mouse model
Authors: Menu Eline , Jernberg-Wiklund Helena , Stromberg Thomas , De Raeve Hendrik , Girnita Leonard , Larsson Olle , Axelson Magnus , Asosingh Kewal , Nilsson Kenneth , Van Camp Ben , Vanderkerken Karin 
Published: July 2005

AbstractInsulin-like growth factor 1 (IGF-1) plays a pleiotropic role in multiple myeloma (MM), that is, in survival, proliferation, chemotaxis, and angiogenesis. Strategies targeting the IGF-1 receptor (IGF-1R) may therefore be important to develop efficient anti-MM agents. In this work we investigated the effect of an IGF-1R tyrosine kinase (IGF-1RTK) inhibitor (picropodophyllin or PPP) in the 5T33MM mouse model. In vitro data showed that PPP reduced IGF-1R autophosphorylation and downstream ERK activation, leading to inhibition of IGF-1–stimulated proliferation and vascular endothelial growth factor (VEGF) secretion of MM cells. In an in vivo study, PPP reduced the bone marrow tumor burden and serum paraprotein in 5T33MM mice by 77% and 90%, respectively, compared to vehicle-treated animals. Angiogenesis was assessed by quantifying the microvessel density on CD31-stained paraffin sections and this was reduced by 60% in the PPP-treated group. In a separate survival experiment, Kaplan-Meier analysis demonstrated a significant increase in survival in PPP-treated 5T33MM animals compared to the vehicle controls (28 versus 18 days). These data suggest that the IGF-1RTK inhibitor PPP possesses a marked antitumor activity and strongly points to the possibility of using IGF-1R inhibitors in the treatment of MM.
The antileukemia effect of HLA-matched NK and NK-T cells in chronic myelogenous leukemia involves NKG2D–target-cell interactions
Authors: Sconocchia Giuseppe , Lau Michelle , Provenzano Maurizio , Rezvani Katayoun , Wongsena Wachanan , Fujiwara Hiroshi , Hensel Nancy , Melenhorst Jos , Li Jonming , Ferrone Soldano , Barrett A. John 
Published: July 2005

AbstractTo study natural killer (NK) cell–mediated antileukemic activity in chronic myelogenous leukemia (CML), we investigated the ability of HLA-matched and mismatched CD56+ cells to inhibit granulocyte macrophage–colony-forming unit (CFU-GM) formation by leukemic CD34+ cells. In 14 HLA-identical donor-recipient pairs, donor CD56+ cells inhibited CML CFU-GM comparably to effectors from 14 HLA-mismatched unrelated individuals (mean inhibition 42% ± 9% vs 39.5% ± 7% at a 10:1 effector-to-target (E/T) ratio), suggesting that killer inhibitory receptor (KIR) incompatibility was not essential for an antileukemic effect. Both CD56+CD3- (natural killer [NK]) and CD56+CD3+(NK-T) cells inhibited CFU-GM growth of CML but not normal CD34+ cells. A mechanism for this leukemia-specific cytotoxicity was suggested by the abnormal overexpression of major histocompatibility class I chain–related gene A or gene B (MICA/B) on CML CD34 cells and their ability to bind the NK activation ligand NKG2D. However, in vivo, CML cells may avoid NK-cell–mediated immune destruction by immune escape, shedding MICA into the plasma, thereby down-regulating NKG2D on CML CD56+ cells.
CD94 1A transcripts characterize lymphoblastic lymphoma/leukemia of immature natural killer cell origin with distinct clinical features
Authors: Lin Chung-Wu , Liu Ting-Yun , Chen Shee-Uan , Wang Kun-Teng , Medeiros L. Jeffrey , Hsu Su-Ming 
Published: July 2005

AbstractMost lymphoblastic lymphomas (LBLs) are regarded as neoplasms of immature T cells because they express cytoplasmic CD3 and frequently carry T-cell receptor (TCR) gene rearrangements. Immature natural killer (NK) and T cells, however, have a common bipotent T/NK-cell precursor in the thymus, and NK cells also express cytoplasmic CD3. Thus, some LBLs could arise from immature NK cells. Mature NK cells express 2 CD94 transcripts: 1A, induced by interleukin 15 (IL-15), and 1B constitutively. Because immature NK cells require IL-15 for development, CD94 1A transcripts could be a marker of NK-LBL. To test this hypothesis, we used laser capture microdissection to isolate IL-15 receptor α+ lymphoid cells from the thymus and showed that these cells contained CD94 1A transcripts. We then assessed for CD94 transcripts in 21 cases of LBL that were cytoplasmic CD3+, nuclear terminal deoxynucleotidyl transferase positive (TdT+), and CD56-, consistent with either the T-cell or NK-cell lineage. We found that 7 LBLs expressed CD94 1A transcripts without TCR gene rearrangements, suggesting NK-cell lineage. Patients with NK-LBL were younger than patients with T-LBL (15 years versus 33 years; P = .11) and had a better 2-year survival (100% versus 27%; P &lt; .01). These results improve the current classification of LBL and contribute to our understanding of NK-cell differentiation.
Targeting MLL-AF4 with short interfering RNAs inhibits clonogenicity and engraftment of t(4;11)-positive human leukemic cells
Authors: Thomas Maria , Geßner Andreas , Vornlocher Hans-Peter , Hadwiger Philipp , Greil Johann , Heidenreich Olaf 
Published: July 2005

AbstractThe chromosomal translocation t(4;11) marks infant acute lymphoblastic leukemia associated with a particularly dismal prognosis. The leukemogenic role of the corresponding fusion gene MLL-AF4 is not well understood. We show that transient inhibition of MLL-AF4 expression with small interfering RNAs impairs the proliferation and clonogenicity of the t(4; 11)–positive human leukemic cell lines SEM and RS4;11. Reduction of mixed-lineage leukemia (MLL)–ALL-1 fused gene from chromosome 4 (AF4) levels induces apoptosis associated with caspase-3 activation and diminished BCL-XL expression. Suppression of MLL-AF4 is paralleled by a decreased expression of the homeotic genes HOXA7, HOXA9, and MEIS1. MLL-AF4 depletion inhibits expression of the stem-cell marker CD133, indicating hematopoietic differentiation. Transfection of leukemic cells with MLL-AF4 siRNAs reduces leukemia-associated morbidity and mortality in SCID mice that received a xenotransplant, suggesting that MLL-AF4 depletion negatively affects leukemia-initiating cells. Our findings demonstrate that MLL-AF4 is important for leukemic clonogenicity and engraftment of this highly aggressive leukemia. Targeted inhibition of MLL-AF4 fusion gene expression may lead to an effective and highly specific treatment of this therapy-resistant leukemia.