bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resolution of Primary Severe Acute Respiratory Syndrome-Associated Coronavirus Infection Requires Stat1
Authors: Hogan Robert J. , Gao Guangping , Rowe Thomas , Bell Peter , Flieder Douglas , Paragas Jason , Kobinger Gary P. , Wivel Nelson A. , Crystal Ronald G. , Boyer Julie , Feldmann Heinz , Voss Thomas G. , Wilson James M. 
Published: September 2004

ABSTRACT
Intranasal inhalation of the severe acute respiratory syndrome coronavirus (SARS CoV) in the immunocompetent mouse strain 129SvEv resulted in infection of conducting airway epithelial cells followed by rapid clearance of virus from the lungs and the development of self-limited bronchiolitis. Animals resistant to the effects of interferons by virtue of a deficiency in Stat1 demonstrated a markedly different course following intranasal inhalation of SARS CoV, one characterized by replication of virus in lungs and progressively worsening pulmonary disease with inflammation of small airways and alveoli and systemic spread of the virus to livers and spleens.
Heterologous Human Immunodeficiency Virus Type 1 Priming-Boosting Immunization Strategies Involving Replication-Defective Adenovirus and Poxvirus Vaccine Vectors
Authors: Casimiro Danilo R. , Bett Andrew J. , Fu Tong-ming , Davies Mary-Ellen , Tang Aimin , Wilson Keith A. , Chen Minchun , Long Romnie , McKelvey Troy , Chastain Michael , Gurunathan Sanjay , Tartaglia Jim , Emini Emilio A. , Shiver John 
Published: September 2004

ABSTRACT

We compared the human immunodeficiency virus type 1 (HIV-1)-specific cellular immune responses elicited in nonhuman primates by HIV-1
gag
-expressing replication-defective adenovirus serotype 5 (Ad5) or poxvirus vectors, used either alone or in combination with each other. The responses arising from a heterologous Ad5 priming-poxvirus boosting regimen were significantly greater than those elicited by homologous regimens with the individual vectors or by a heterologous poxvirus priming-Ad5 boosting regimen. The heterologous Ad5 priming-poxvirus boosting approach may have potential utility in humans as a means of inducing high levels of cellular immunity.
Four EBNA2 Domains Are Important for EBNALP Coactivation
Authors: Peng Chih-Wen , Zhao Bo , Kieff Elliott 
Published: September 2004

ABSTRACT
EBNA2 transcriptional activation and regulated EBNALP coactivation are critical for Epstein-Barr virus-infected primary B-lymphocyte growth transformation. EBNALP coactivation requires the EBNA2 acidic activation domain (E2AD); EBNALP can bind to E2AD. EBNALP has now been found to bind less well to EBNA2 amino acids 1 to 58, which has been identified to be a second transcriptional activation domain, E2AD2. E2AD2 was specifically coactivated by EBNALP. Moreover, E2AD, E2AD2, EBNA2 RG domain, and the intermediate domain between RG and E2AD had significant roles in EBNA2-mediated activation and EBNALP coactivation.
Myristoylation of the RING Finger Z Protein Is Essential for Arenavirus Budding
Authors: Perez Mar , Greenwald Dori L. , de La Torre Juan Carlos 
Published: September 2004

ABSTRACT

The arenavirus small RING finger Z protein is the main driving force of arenavirus budding. The primary structure of Z is devoid of hydrophobic transmembrane domains, but both lymphocytic choriomeningitis virus (LCMV) and Lassa fever virus Z proteins accumulate near the inner surface of the plasma membrane and are strongly membrane associated. All known arenavirus Z proteins contain a glycine (G) at position 2, which is a potential acceptor site for a myristoyl moiety. Metabolic labeling showed incorporation of [
3
H]myristic acid by wild-type Z protein but not by the G2A mutant. The mutation G2A eliminated Z-mediated budding. Likewise, treatment with the myristoylation inhibitor 2-hydroxymyristic acid inhibited Z-mediated budding, eliminated formation of virus-like particles, and caused a dramatic reduction in virus production in LCMV-infected cells. Budding activity was restored in G2A mutant Z proteins by the addition of the myristoylation domain of the tyrosine protein kinase Src to their N termini. These findings indicate N-terminal myristoylation of Z plays a key role in arenavirus budding.
Troponin I, laboratory issues, and clinical outcomes in a district general hospital: crossover study with “traditional” markers of myocardial infarction in a total of 1990 patients
Authors: Jishi F , Hudson P R , Williams C P , Jones R P , Davies G K , Yousef Z R , Trent R J , Cowell R P W 
Published: September 2004

Aims:Review of the clinical outcomes and practical issues of replacing traditional cardiac enzymes with troponin I (cTnI) in a district general hospital.Methods:Crossover study of three sequential three month stages during which serial cardiac enzymes were replaced with a single cTnI measurement available at three set times within 24 hours for the duration of the second three month stage. The study was carried out in a 630 bed district general hospital with 1990 admissions of suspected cardiac ischaemia over the study period as a whole. Account was taken of seasonal factors.Results:The introduction of troponin was associated with 8.5% more patients with non-ischaemic heart disease (IHD) being discharged on the day after admission, saving approximately 107 bed days each year. Approximately 50% more patients were diagnosed with myocardial infarction during the cTnI stage. There was no increase in readmission within one month or early death with cTnI. Approximately 3% false positive and 1.5% false negative cTnI results were recorded. All false positive cTnI results were coding errors or attributable to known assay interference effects. All false negatives were potentially explained by sample timing factors. The lack of standardisation in troponin assay services impacts clinically.Conclusion:Younger patients without IHD were discharged earlier during the cTnI stage in apparent safety. Blood sample timing needs to be verified when cTnI is used as an adjunct to early discharge. There were no unexplained false positives or negatives. Standardisation related issues arose.
Gastrin releasing peptide receptor expression is decreased in patients with Crohn’s disease but not in ulcerative colitis
Authors: ter Beek W P , Muller E S M , van Hogezand R A , Biemond I , Lamers C B H W 
Published: September 2004

Background:Gastrin releasing peptide (GRP) and neuromedin B are bombesin (BN)-like peptides involved in regulating motility and inflammation in the gastrointestinal tract, which may be useful in treating inflammatory bowel disease (IBD). Three bombesin-like peptide receptors have been reported, but no studies have investigated their localisation in normal and inflamed human intestine.Aim:To localise and characterise BN receptors in normal intestine and to see whether this is modified in IBD.Methods:Full thickness intestinal tissue samples were collected from 13 patients with Crohn’s disease (CD), 11 with ulcerative colitis (UC), and 19 controls. BN receptor expression was characterised and quantified with storage phosphor autoradiography using BN, GRP, neuromedin B, and the synthetic analogue BN(6–14) as ligands.Results:Only BN receptor type 2 (high affinity for GRP) was present in intestinal tissue. Minimal BN binding was detected in the mucosa. In normal colonic smooth muscle, mean BN binding was 336 fmol/g tissue in longitudinal muscle, including the myenteric plexus, and 71 fmol/g in circular muscle. In CD, colonic smooth muscle BN binding was significantly decreased (longitudinal muscle, 106; circular muscle, 19 fmol/g), in contrast to UC (377 and 62 fmol/g, respectively). In CD, a small (not significant) decrease was seen in ileal muscle compared with controls (111v169 and 18v32 fmol/g tissue for longitudinal and circular muscle, respectively).Conclusions:Only the GRP receptor is expressed in human intestine; expression is highest in longitudinal muscle and myenteric plexus of the colon. Expression is decreased in inflamed and non-inflamed colon of CD, but not in UC.
The homeodomain protein CDX2 is an early marker of Barrett’s oesophagus
Authors: Moons L M G , Bax D A , Kuipers E J , van Dekken H , Haringsma J , van Vliet A H M , Siersema P D , Kusters J G 
Published: September 2004

Background:In Barrett’s oesophagus (BO), squamous epithelium is replaced by specialised intestinal epithelium (SIE). Transcription factors associated with intestinal differentiation, such as CDX2, may be involved in BO development.Aim:To investigate CDX2 expression in BO, squamous epithelium, and oesophageal adenocarcinoma (ADC).Methods:CDX2 expression was assessed in 245 samples—167 biopsies of the columnar lined segment and 38 squamous epithelial biopsies of 39 patients with histologically confirmed BO (10 with ADC). Forty biopsies from 20 patients with reflux oesophagitis (RO) without BO were also evaluated. CDX2 protein was investigated immunohistochemically in 138 biopsies from 16 patients with BO, four with ADC, and 20 with RO. Cdx2 and Muc2 mRNA were detected semiquantitatively using 88 BO biopsies and squamous epithelium from 19 BO patients, and when present from ADC.Results:SIE was present in 53/79 biopsies from the columnar lined segment; CDX2 protein was seen in all epithelial cells, but not in biopsies containing only gastric metaplastic epithelium (26/79), or in squamous epithelium (0/40) of patients with RO. Cdx2 mRNA was detected in all biopsies with goblet cell specific Muc2 transcription—indicative of SIE. Low Cdx2 mRNA expression was seen in 6/19 squamous epithelium samples taken 5 cm above the squamocolumnar junction of BO patients.Conclusion:CDX2 protein/mRNA is strongly associated with oesophageal SIE. Cdx2 mRNA was present in the normal appearing squamous epithelium of one third of BO patients, and may precede morphological changes seen in BO. Therefore, pathways that induce Cdx2 transcription in squamous epithelial cells may be important in BO development.
How should stainable iron in bone marrow films be assessed?
Authors: Hughes D A , Stuart-Smith S E , Bain B J 
Published: September 2004

Aims:To identify how many particles should be examined to enable a confident assessment of the presence or absence of iron stores and the quantity of iron in a bone marrow aspirate to be made.Methods:One hundred and ninety consecutive bone marrow aspirate samples were stained with Perls’ stain and the iron content of 10 consecutive particles was recorded. The first particle found to be positive and the particle that was most positive were also noted.Results:A minimum of seven particles must be examined to establish the absence of stainable iron. A minimum of nine particles must be reviewed to see the maximum iron stores in 100% of samples and therefore make a valid judgment of whether iron stores are reduced, normal, or increased. By these criteria, 46% of the samples tested here could not be optimally assessed for absence of iron or maximum iron stores.Conclusions:The sensitivity of examination of bone marrow aspirates for iron stores can be optimised by increasing the number of particles reviewed to seven or more. This may require the staining of additional slides.
c-KIT and PDGFRA in breast phyllodes tumours: overexpression without mutations?
Authors: Carvalho S , Silva A O e , Milanezi F , Ricardo S , Leitão D , Amendoeira I , Schmitt F C 
Published: September 2004

Aim:To study the immunoexpression and mutational status of c-KIT and PDGFRA in a series of benign and malignant phyllodes tumours of the breast.Material/methods:Nineteen phyllodes tumours (13 benign and six malignant) were analysed by immunohistochemistry for the expression of c-KIT and PDGFRA. Direct sequencing of exons 9, 11, 13, and 17 of the c-KIT gene and exons 12 and 18 of PDGFRA was performed to check the mutational status of these two genes.Results:c-KIT expression was found in 12 of the 19 cases (six of the 13 benign cases and all six malignant ones) and PDGFRA expression was seen in two of the 19 cases (one benign and one malignant case); the 2415 C>T alteration in exon 17 of the c-KIT gene was found in two cases (both benign); the intronic insertion IVS17-50insT and the 2866 G>T alteration in the coding region of exon 18 of the PDGFRA gene were also found in two cases (one malignant and one benign). However, the activating mutations described for these genes in gastrointestinal stromal tumours were not present.Conclusion:c-KIT expression is a frequent finding in phyllodes tumours, particularly in malignant cases; however, no activating mutations similar to those described for gastrointestinal stromal tumours were found. The PDGFRA does not seem to be an alternative pathway to tumour development in phyllodes tumours because neither expression nor activating mutations were noteworthy.
DNA replication regulation protein Mcm7 as a marker of proliferation in prostate cancer
Authors: Padmanabhan V , Callas P , Philips G , Trainer T D , Beatty B G 
Published: September 2004

Background:Recent studies have shown that minichromosome maintenance (MCM) proteins (Mcm2–7) may be useful proliferation markers in dysplasia and cancer in various tissues.Aims:To investigate the use of Mcm7 as a proliferation marker in 79 lymph node negative prostate cancers and compare it with Ki-67, a commonly used cell proliferation marker.Methods:The percentage of proliferating cells (proliferation index; PI) was calculated for basal and luminal epithelial cells in benign prostate tissue, prostatic intraepithelial neoplasia (PIN), and epithelial cells in adenocarcinoma. The PI for each biomarker was correlated with the preoperative prostate specific antigen concentration, the Gleason score, surgical resection margin status, and the AJCC pT stage for each patient.Results:The mean PIs for Ki-67 and Mcm7 were: benign luminal epithelium 0.7 and 1.2 and benign basal epithelium 0.8 and 8.2; PIN non-basal epithelium 4.9 and 10.6 and PIN basal epithelium 0.7 and 3.1; adenocarcinoma 9.8 and 22.7, respectively. Mcm7 had a significantly higher mean PI (p<0.0001) than Ki-67 for all cell categories except benign luminal epithelial cells. Mcm7 was a better discriminatory marker of proliferation between benign epithelium, PIN, and invasive adenocarcinoma (p<0.0001) than Ki-67. The drop in Mcm7 mean basal cell PI from benign epithelium to PIN epithelium was significantly larger than for Ki-67 (p<0.0001). Mcm7 had a significantly higher PI than Ki-67 at each risk level.Conclusion:Mcm7 may be a useful proliferation marker in prostatic neoplasia and warrants further evaluation as a complementary tool in the diagnosis of PIN and prostate carcinoma.
Proximal versus distal hyperplastic polyps of the colorectum: different lesions or a biological spectrum?
Authors: Baker K , Zhang Y , Jin C , Jass J R 
Published: September 2004

Background:Because of their suggested link with microsatellite instability high colorectal cancers, right sided hyperplastic polyps (HPs) may differ from their distally located counterparts. This is highlighted by the recognition of a variant HP, termed sessile serrated adenoma (SSA), which predominates in the proximal colon. HPs displaying the morphological features now associated with SSAs have been shown to have altered expression of “cancer associated” markers, but no studies have investigated whether this is dependent on anatomical location of the polyps.Aims:To evaluate morphological and functional features in right versus left sided HPs from patients without colorectal cancer with the aim of identifying distinguishing characteristics.Methods:HPs originating in the proximal and distal colorectum were histochemically and immunohistochemically stained to evaluate a panel of markers related to proliferation and differentiation. In addition, a series of morphological features was evaluated for each polyp.Results:Crypt serration, crypt dilatation, and horizontal crypt growth were more common among HPs from the right side, whereas histochemical factors including mucin changes, global methylation status, and expression of carcinoembryonic antigen were not significantly different. An age disparity was also seen between patients with right versus left sided lesions, with patients with right sided lesions being an average of more than 10 years younger than those with left sided lesions.Conclusions:These findings suggest that right and left sided HPs differ mainly in terms of growth regulation rather than cellular differentiation, implying that these lesions belong to a continuous spectrum of serrated polyps that differ quantitatively rather than qualitatively.
Expression of SRC-1, AIB1, and PEA3 in HER2 mediated endocrine resistant breast cancer; a predictive role for SRC-1
Authors: Fleming F J , Myers E , Kelly G , Crotty T B , McDermott E W , O’Higgins N J , Hill A D K , Young L S 
Published: September 2004

Background:In human breast cancer, the growth factor receptor HER2 is associated with disease progression and resistance to endocrine treatment. Growth factor induced mitogen activated protein kinase activity can phosphorylate not only the oestrogen receptor, but also its coactivator proteins AIB1 and SRC-1.Aim:To determine whether insensitivity to endocrine treatment in HER2 positive patients is associated with enhanced expression of coactivator proteins, expression of the HER2 transcriptional regulator, PEA3, and coregulatory proteins, AIB1 and SRC-1, was assessed in a cohort of patients with breast cancer of known HER2 status.Methods:PEA3, AIB1, and SRC-1 protein expression in 70 primary breast tumours of known HER2 status (HER2 positive, n = 35) and six reduction mammoplasties was assessed using immunohistochemistry. Colocalisation of PEA3 with AIB1 and SRC-1 was determined using immunofluorescence. Expression of PEA3, AIB1, and SRC-1 was correlated with clinicopathological parameters.Results:In primary breast tumours expression of PEA3, AIB1, and SRC-1 was associated with HER2 status (p = 0.0486, p = 0.0444, and p = 0.0012, respectively). In the HER2 positive population, PEA3 expression was associated with SRC-1 (p = 0.0354), and both PEA3 and SRC-1 were significantly associated with recurrence on univariate analysis (p = 0.0345; p<0.0001). On multivariate analysis, SRC-1 was significantly associated with disease recurrence in HER2 positive patients (p = 0.0066).Conclusion:Patients with high expression of HER2 in combination with SRC-1 have a greater probability of recurrence on endocrine treatment compared with those who are HER2 positive but SRC-1 negative. SRC-1 may be an important predictive indicator and therapeutic target in breast cancer.
Reversal of glandular polarity in the lymphovascular compartment of breast cancer
Authors: Adams S A , Smith M E F , Cowley G P , Carr L A 
Published: September 2004

Aim:To investigate the polarity of breast invasive ductal carcinoma cells by comparing the polarity of the tumour located within lymphovascular spaces with that located in the extravascular compartment.Methods:An immunohistochemical study identifying the apical HMFG-1, basolateral AUA-1, and basal laminin polarity markers of 11 cases of invasive ductal carcinoma (grades 1 or 2) metastatic to lymph nodes, all of which contained areas of tumour within and outside of lymphovascular spaces.Results:Only one of 11 tumours had a focus of apparent reversed glandular polarity in the larger extravascular tumour compartment (with AUA-1 present internally and HMFG-1 expressed externally on tumour clumps), but six of the 11 tumours showed reversed glandular polarity (either with AUA-1, or HMFG-1, or both) within the very much smaller lymphovascular space tumour compartment. Laminin was not identified in association with lymphovascular tumour.Conclusions:Reversed glandular polarity in invasive ductal breast carcinomas was identified and was significantly more frequent within vessels than outside of them. Reversal of tumour glandular polarity within lymphovascular spaces allows direct interaction between apical domain-type molecules—which are then aberrantly expressed on the external surface of tumour clumps—and lymphovascular endothelium. Such interactions may affect the establishment of metastatic disease.
Haptoglobin genotypic distribution (including Hp0allele) and associated serum haptoglobin concentrations in Koreans
Authors: Park K U , Song J , Kim J Q 
Published: September 2004

Background:Haptoglobin polymorphism is associated with the prevalence of infections, autoimmune diseases, cardiovascular diseases, and other disorders. Congenital haptoglobin deficiency is associated with anaphylactic transfusion reactions in anhaptoglobinaemic patients with antihaptoglobin antibody.Aims:To investigate haptoglobin genotypic distribution (including the Hp0allele) and associated serum haptoglobin concentrations in Koreans.Methods:Five hundred and nine healthy Korean adults were randomly selected. Two methods were used: haptoglobin genotyping based on a polymerase chain reaction (PCR) system that exploited the structural difference of the Hp1and Hp2alleles, and another PCR method that detected haptoglobin gene deletion by amplification of the junctional region of the Hp0allele. Serum haptoglobin concentrations were measured by nephelometry.Results:The haptoglobin genotypes of 509 subjects were as follows: Hp1Hp1, 7.1%; Hp2Hp1, 37.7%; Hp2Hp2, 49.3%; Hp0Hp1, 2.2%; Hp0Hp2, 3.5%; Hp0Hp0, 0.2%. The gene frequency of Hp0in Koreans was calculated to be 0.031. Significant differences were seen among the concentrations of each haptoglobin genotype (Kruskal-Wallis test). Hp0Hp2, but not Hp0Hp1, was associated with hypohaptoglobinaemia.Conclusions:PCR methods for differentiating between haptoglobin genotypes, including the Hp0allele, may be useful in a broad spectrum of basic studies and clinical examinations.
Papillary carcinoma of the thyroid in Japan: subclassification of common type and identification of low risk group
Authors: Kakudo K , Tang W , Ito Y , Mori I , Nakamura Y , Miyauchi A 
Published: September 2004

Aims:Papillary thyroid carcinoma (PTC) is classified into two subgroups—common type and other histological variants. Correlations between further subgrouping of the common type and patient prognosis are not well documented.Aims:To introduce two novel histological parameters to characterise PTC—loss of cellular polarity and loss of cellular cohesiveness. To investigate a new subgroup of common type PTC with possible prognostic value.Methods:In total, 213 patients with PTCs larger than 1 cm were studied. Histological characteristics of these PTCs, including tumour growth pattern, encapsulation, extrathyroidal invasion, loss of cellular polarity, and loss of cellular cohesiveness were examined and correlated with disease free survival (DFS).Results:Multivariate analysis revealed that invasive growth of unencapsulated PTC, in addition to sex (male) and tumour size (>4 cm) were significant and independent parameters for poor DFS, whereas loss of cellular polarity and cohesiveness, old age (>60 years), extrathyroid invasion, and completeness of surgery were significant only in univariate analysis. PTCs that showed expansive growth and retained cellular polarity had a favourable course, with no recurrence and no cancer related deaths. In contrast, PTCs exhibiting loss of cellular polarity and/or invasive growth with no tumour capsule had a higher risk of recurrence.Conclusion:Cytological features alone cannot predict patient outcome in PTC. This study indicates for the first time that loss of cellular polarity and the tumour growth pattern are useful parameters for identifying the so called low risk group in common type PTC and in predicting patient outcome in terms of tumour recurrence and cancer related death.