bluuebunny/crossref_metadata_2025 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

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

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

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

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.
Mucosal immunology of vaccines against pathogenic nasopharyngeal bacteria
Authors: Zhang Q , Finn A
Published: September 2004

The introduction ofHaemophilus influenzaetype b conjugate vaccines during the 1990s was followed by dramatic decreases both in the incidence ofHaemophilus influenzaetype b related invasive disease and in nasopharyngeal carriage of the organism. The extent of this effect has been influenced by the fact thatHaemophilus influenzaetype b conjugate vaccines reduce nasopharyngeal carriage and induce herd immunity. Based on the success ofHaemophilus influenzaetype b conjugate vaccines, chemical conjugation has been applied to the development of pneumococcal and meningococcal polysaccharide conjugate vaccines. Evidence has begun to accumulate that these new polysaccharide based conjugate vaccines can also reduce nasopharyngeal carriage and can induce immune responses at the local mucosal level, which may be responsible for these effects. This article reviews recent studies on mucosal immune responses induced by polysaccharide based vaccines and some protein vaccine antigens against several pathogenic nasopharyngeal bacteria, and discusses the mechanisms and functions of these immune responses that may help our understanding of mucosal immune responses to both immunisation and infection.
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.
Spurious rise in the automated platelet count because of bacteria: Figure 1
Authors: Kakkar N
Published: September 2004

The era of automation in haematology, although improving the accuracy and precision of results, has also introduced the laboratory haematologist to a vast array of spurious parameters. The identification of these results is important so that inappropriate management decisions are avoided. The case presented here illustrates a spuriously raised automated platelet count resulting from bacterial overgrowth in the blood sample.
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.
Spectrum of lymph node pathology in adult onset Still’s disease; analysis of 12 patients with one follow up biopsy
Authors: Jeon Y K , Paik J H , Park S-S , Park S O , Kim Y A , Kim J E , Song Y W , Kim C W
Published: September 2004

Background:Adult onset Still’s disease (AOSD) is a rare systemic inflammatory disorder of unknown aetiology, frequently accompanying multiple lymphadenopathy. It often mimics malignant lymphoma, and immunohistochemical and molecular studies are needed for definite diagnosis.

Aims:To aid in diagnosis and understand the pathogenesis of the disease by clarifying lymph node (LN) pathology in AOSD.

Methods:Thirteen biopsies (one follow up biopsy) and medical records of 12 patients were reviewed. Immunohistochemistry, polymerase chain reaction for T cell receptor γ chain (TCRγ) and immunoglobulin heavy chain gene rearrangement, and Epstein-Barr virus in situ hybridisation were performed.

Results:Histologically, LN lesions were classified into four patterns. The most common (six biopsies) showed paracortical hyperplasia, with prominent vascular proliferation, scattered large B/T immunoblasts, and infiltration by reactive lymphocytes and inflammatory cells. In the second pattern (two biopsies), paracortical hyperplasia was accompanied by massive sinus histiocytosis and S-100 positive histiocyte aggregates. The third pattern (three patients) showed an exuberant immunoblastic reaction, in the form of patchy/diffuse infiltration of large T immunoblasts with high mitotic activity, although clonal rearrangement of the TCRγ gene was not detected. The fourth pattern showed distinct follicular hyperplasia (two cases). One patient with a follow up biopsy showed a pattern change from pronounced follicular hyperplasia to atypical paracortical hyperplasia.

Conclusions:AOSD LN lesions show a dynamic histological spectrum, including atypical paracortical hyperplasia, burnt out histiocytic reaction, exuberant immunoblastic reaction, and follicular hyperplasia. During the course of disease, LN reactivity changes and mixed B and T cells are involved in the pathogenesis.
Expression of mismatch repair proteins, β catenin, and E cadherin in intestinal-type sinonasal adenocarcinoma
Authors: Perez-Ordonez B , Huynh N N , Berean K W , Jordan R C K
Published: September 2004

Background:Despite their histological resemblance to colorectal adenocarcinomas, there is little information about the molecular events involved in the pathogenesis of intestinal-type sinonasal adenocarcinomas (ITACs).

Aims:To evaluate the possible role of DNA mismatch repair (MMR) gene defects or disruptions of the E cadherin–β catenin complex in ITAC by investigating the immunohistochemical expression of the MMR gene products, β catenin, and E cadherin in a group of sporadic ITACs.

Methods:Ten sporadic cases of ITAC were stained with antibodies against MLH1, MSH2, MSH3, MSH6, β catenin, and E cadherin.

Results:Nine cases showed strong nuclear expression of MLH1, whereas one case showed moderate staining. All 10 cases were strongly positive for MSH2 and MSH3. MSH6 was strong in nine cases, and moderate in one. Membranous β catenin expression was strong in all 10 cases, and no case showed cytoplasmic or nuclear staining. E cadherin was strong in seven cases, and moderate in three cases.

Conclusions:The preserved nuclear expression of MLH1, MSH2, MSH3, and MSH6 suggests that mutations or promoter methylation of MMR genes do not play a role in the pathogenesis of ITAC. The strong membranous staining for E cadherin and β catenin and lack of abnormal cytoplasmic or nuclear expression is in keeping with the preservation of E cadherin–β catenin complexes and β catenin pathways.
Pancreatic endocrine tumour with cytoplasmic keratin whorls. Is the term “rhabdoid” appropriate?
Authors: Chetty R , Asa S L
Published: September 2004

A 50 year old woman presented with acute abdominal pain accompanied by nausea and vomiting and was found to have a mass in the head of the pancreas by imaging. The clinical impression was of a pancreatic carcinoma and a Whipple’s procedure was performed. Microscopic examination of the tumour showed it to be a low grade neuroendocrine carcinoma arranged in a tubuloacinar or tubulopapillary pattern, and composed of cells harbouring very prominent intracytoplasmic inclusions. These inclusions varied in appearance from being pale pink and hyaline in quality to more eosinophilic and globular causing displacement of the nucleus. Ultrastructural examination showed typical paranuclear aggregates of intermediate filaments. Inclusions of this type have been described previously as “signet ring like” and “rhabdoid”. It was felt that the inclusions more closely resemble the fibrous bodies that are seen in pituitary adenomas. In addition, it is suggested that both signet ring and rhabdoid are not appropriate because they do not reflect histogenesis and are not necessarily reflective of tumour biology. It is suggested that the term “cytokeratin aggresomes” should be used to describe this distinctive phenotype.
Fatal renal failure as the first manifestation of sarcoidosis diagnosed on necropsy in a young man: a case report
Authors: Awasthi A , Nada R , Malhotra P , Goel R , Joshi K
Published: September 2004

Renal involvement as the first manifestation of sarcoidosis is rare and has never been reported in India. This report describes a 35 year old man who was admitted to the emergency department with a clinical diagnosis of acute on chronic renal failure, secondary to obstructive uropathy. Postmortem examination unexpectedly revealed disseminated sarcoidosis.
Comparative molecular pathology of sporadic hyperplastic polyps and neoplastic lesions from the same individual
Authors: Zauber P , Sabbath-Solitare M , Marotta S , Zauber A , Bishop T
Published: September 2004

Aim:The biology of colorectal hyperplastic polyps is of considerable relevance, because recent evidence suggests that under certain circumstances hyperplastic polyps may be precursors of neoplasms. The aim of this study was to assess and compare the clinical and molecular characteristics of hyperplastic polyps and neoplastic lesions removed from patients without the hyperplastic polyposis syndrome.

Methods:One hundred and twenty six patients were identified through a series of genetic epidemiological studies. Each patient had at least one neoplastic lesion and one hyperplastic polyp; there was a total of 147 hyperplastic polyps. All lesions were evaluated for K-ras mutations, loss of heterozygosity (LOH) of the adenomatous polyposis coli (APC) gene, and microsatellite instability.

Results:K-ras mutation was detected in 15 (10%) hyperplastic polyps, all from the rectosigmoid colon. No hyperplastic polyp had APC LOH or microsatellite instability. Patients with adenomas or carcinomas showing K-ras mutations were not more likely to have hyperplastic polyps with K-ras mutations. The average number of adenomas did not differ between those patients with hyperplastic polyps with K-ras mutations and those without K-ras mutations. There was no association between the hyperplastic polyp and the adenoma regarding the colon segments from which the two lesions were removed.

Conclusions:The sporadic hyperplastic polyp is a lesion with limited molecular change and no relation to patients’ neoplastic lesions.
LARGE SCALE AIR SHOWER SIMULATIONS AND THE SEARCH FOR NEW PHYSICS AT AUGER
Authors: CAFARELLA ALESSANDRO , CORIANÒ CLAUDIO , FARAGGI ALON E.
Published: September 2004

Large scale airshower simulations around the GZK cutoff are performed. An extensive analysis of the behaviour of the various subcomponents of the cascade is presented. We focus our investigation both on the study of total and partial multiplicities along the entire atmosphere and on the geometrical structure of the various cascades, in particular on the lateral distributions. The possibility of detecting new physics in Ultra High Energy Cosmic Rays (UHECR) at AUGER is also investigated. We try to disentangle effects due to standard statistical fluctuations in the first proton impact in the shower formation from the underlying interaction and comment on these points. We argue that theoretical models predicting large missing energy may have a chance to be identified, once the calibration errors in the energy measurements are resolved by the experimental collaborations, in measurements of inclusive multiplicities.
LIFETIME DIFFERENCE AND ENDPOINT EFFECT IN THE INCLUSIVE BOTTOM HADRON DECAYS
Authors: ZUO Y. B. , YAN Y. A. , WU Y. L. , WANG W. Y.
Published: September 2004

The lifetime differences of bottom hadrons are known to be properly explained within the framework of heavy quark effective field theory (HQEFT) of QCD via the inverse expansion of the dressed heavy quark mass. In general, the spectrum around the endpoint region is not well behaved due to the invalidity of 1/mQ expansion near the endpoint. The curve fitting method is adopted to treat the endpoint behavior. It turns out that the endpoint effects are truly small and the explanation on the lifetime differences in the HQEFT of QCD is then well justified. The inclusion of the endpoint effects makes the prediction on the lifetime differences and the extraction on the CKM matrix element |Vcb| more reliable.
LOGARITHMIC PERTURBATION THEORY FOR RADIAL KLEIN–GORDON EQUATION WITH SCREENED COULOMB POTENTIALS VIA ℏ-EXPANSIONS
Authors: DOBROVOLSKA I. V. , TUTIK R. S.
Published: September 2004

The explicit semiclassical treatment of logarithmic perturbation theory for the bound-state problem within the framework of the radial Klein–Gordon equation with attractive screened Coulomb potentials, contained time-component of a Lorentz four-vector and a Lorentz-scalar term, is developed. Based upon ℏ-expansions and new quantization conditions a novel procedure for deriving perturbation expansions is offered. Avoiding disadvantages of the standard approach, new handy recursion formulae with the same simple form both for ground and excited states have been obtained. As an example, the perturbation expansions for the energy eigenvalues for the Hulthén potential containing the vector part as well as the scalar component are considered.
PARTICLE PRODUCTION ON HALF S-BRANE
Authors: KLUSOŇ J.
Published: September 2004

In this paper we will study quantum field theory of fluctuation modes around the rolling tachyon solution on non-BPS D-brane effective action. The goal of this paper is to study particle production during the decay of non-BPS D-brane and explore possible relation with minisuperspace calculation. We find that the number of particles produced on half S-brane exponentially grows for large time which suggests that linearized approximation breaks down and also that backreaction of fluctuation field on classical solution should be taken into account.
SUPERCONFORMAL ORBIFOLDS INVOLVING THE FERMION NUMBER OPERATOR
Authors: WENDLAND KATRIN
Published: September 2004

We consider orbifolds of two-dimensional unitary toroidal superconformal field theories with target spaces of arbitrary dimensions, where the orbifold group involves the space–time fermion number operator. We construct all so-called superaffine, orbifold prime and super-M-orbifold models by generalizing the constructions of Dixon, Ginsparg and Harvey. We also correct claims made by Dixon, Ginsparg and Harvey about multicritical points among those models with central charge [Formula: see text].
HISTOLOGICAL ASSESSMENT OF THE CHONDRAL AND CONNECTIVE TISSUES OF THE KNEE BY CONFOCAL ARTHROSCOPE
Authors: Jones C. W. , Keogh A. , Smolinski D. , Wu J. P. , Kirk T. B. , Zheng M. H.
Published: September 2004

Conventional histological assessment of tissue requires the removal of tissue from its physiological environment for pathological processing. In this study we report on the development and application of a laser scanning confocal arthroscope (LSCA) capable of in situ histological assessment by confocal microscopy.

The knee joints of three euthanasied adult Merino sheep were imaged using the LSCA and a combination of fluorescent contrasting agents. LSCA images of various tissues were examined for common histological characteristics.

The confocal histology images from the ovine knee acquired during the course of our study illustrated some of the major histological features of chondral and connective tissues.

Our study demonstrates the efficacy of the LSCA for the histological assessment of the chondral and connective tissues of the ovine knee. The LSCA provides an easy and rapid method for assessing the in situ structure of cartilage, muscle, tendon, ligament, meniscus and synovium in their native and unaltered physiological environment. By obviating the need for mechanical biopsy, the LSCA provides a method for the non-destructive assessment of the chondral and connective tissues of the knee, and may be of great benefit in the investigation of orthopedic diseases or in the assessment of newly emerging cartilage repair techniques.
PREDICTION OF BIOMECHANICAL CHARACTERISTICS OF INTACT AND INJURED LOWER THORACIC SPINE SEGMENT UNDER DIFFERENT LOADS
Authors: Guo Li-Xin , Teo Ee-Chon , Qiu Tian-Xia
Published: September 2004

In this study, the biomechanical roles of disc nucleus and ligaments of human lower thoracic spine (T10–T12) under different loads were investigated using finite element (FE) method. The T10–T12 FE model was developed and validated against the published results. The FE model was then modified accordingly to simulate the injured conditions of nucleus, ligaments and facets and loaded under different configurations to analyze the segmental gross responses and the stress distribution around the annulus circumference. The high first-principal stress of annulus at the posterolateral region has an important role on the disc annulus's tear and a flexion moment causes a high first-principal stress at posterolateral region, despite of the existence of ligaments. The study also shows that decompression in intervertebral discs can reduce the dilatation of annulus tears by 18% around the posterolateral regions of disc annulus. The disc nucleus and the posterior ligaments have important roles in resisting compression and flexion loads, respectively. The investigations in this paper not only supplement experimental research but are also helpful in the understandings of biomechanics of lower thoracic spine.
Deutsche Siedler im Tiflis des 19. Jahrhunderts
Authors: Tschogoschwili Nino
Published: September 2004

The article sheds a new light on the history of German settlers in Tiflis of the 19th century. The main focus lies on emphasizing the important role these settlers played in cultural and economic life of the city. The records the emigrants left behind, depict in vivid tints the circumstances of their existence. Most of the Germans in Tiflis were craftsmen and merchants, others earned their life, for instance, as teacher, scientist, pastor, painter, musician or as enterpriser and man of business. Short biographies of some of the most outstanding characters round off the article.
Stability Analysis of Legged Locomotion Models by Symmetry-Factored Return Maps
Authors: Altendorfer Richard , Koditschek Daniel E. , Holmes Philip
Published: September 2004

We present a new stability analysis for hybrid legged locomotion systems based on the “symmetric” factorization of return maps. We apply this analysis to two-degrees-of-freedom (2DoF) and three-degrees-of-freedom (3DoF) models of the spring loaded inverted pendulum (SLIP) with different leg recirculation strategies. Despite the non-integrability of the SLIP dynamics, we obtain a necessary condition for asymptotic stability (and a sufficient condition for instability) at a fixed point, formulated as an exact algebraic expression in the physical parameters. We use this expression to characterize analytically the sensory cost and stabilizing benefit of various feedback schemes previously proposed for the 2DoF SLIP model, posited as a low-dimensional representation of running. We apply the result as well to a 3DoF SLIP model that will be treated at greater length in a companion paper as a descriptive model for the robot RHex.
Stability Analysis of a Clock-Driven Rigid-Body SLIP Model for RHex
Authors: Altendorfer Richard , Koditschek Daniel E. , Holmes Philip
Published: September 2004

We apply the stability analysis for hybrid legged locomotion systems, introduced in our companion paper in this issue, to a new simple clock-driven SLIP model inspired by the robot RHex. We adopt in stance phase the three-degrees-of-freedom (3DoF) spring loaded inverted pendulum (SLIP) model introduced in our companion paper to capture RHex’s pitching dynamics in the sagittal plane. The coordinating influence of RHex’s open-loop clock controller is subsumed into a leg placement strategy derived from a bipedal abstraction of RHex. The “symmetric” factorization analysis introduced in our companion paper yields a necessary condition for gait stability expressed in closed form, which can be imposed directly on the clock parameter space. This represents the first reported analytical insight into how a dynamical runner might be stabilized by a completely feed forward rhythmic limb coordination pattern. Correspondence in steady-state gait location and stability characteristics with an appropriately tuned 24DoF model of RHex provides numerical evidence that the 3DoF SLIP model offers a descriptive explanation for the robot’s empirical running behavior.
Traction Control of Wheeled Robotic Vehicles in Rough Terrain with Application to Planetary Rovers
Authors: Iagnemma Karl , Dubowsky Steven
Published: September 2004

Mobile robots are being developed for high-risk missions in rough terrain situations, such as planetary exploration. Here, a rough-terrain control methodology is presented that exploits the actuator redundancy found in multiwheeled mobile robot systems to improve ground traction and reduce power consumption. The algorithm optimizes individual wheel torque based on multiple optimization criteria, which are a function of the local terrain profile. A key element of the method is to be able to include estimates of wheel-terrain contact angles and soil characteristics. A method using an extended Kalman filter is presented for estimating these angles using simple on-board sensors. Simulation and experimental results for a micro-rover traversing challenging terrain demonstrate the effectiveness of the algorithm.
Robust Cascade Controller for Nonlinearly Actuated Biped Robots: Experimental Evaluation
Authors: Caballero Rony , Armada Manuel A. , Akinfiev Teodor
Published: September 2004

In this paper we consider the postural stability problem for nonlinearly actuated quasi-static biped robots, both with respect to the joint angular positions and also with reference to the gripping effect between the foot/feet against the ground during robot locomotion. Zero moment point based mathematical models are developed to establish a relationship between the robot state variables and the stability margin of the foot (feet) contact surface and the supporting ground. Then, in correspondence with the developed dynamical model and its associated uncertainty, and in the presence of non-modeled robot mechanical structure vibration modes, we propose a robust control architecture that uses two cascade regulators. The overall robust control system consists of a nonlinear robust variable structure controller in an inner feedback loop for joint trajectory tracking, and an H∞ linear robust regulator in an outer, direct zero moment point feedback loop to ensure the foot-ground contact stability. The effectiveness of this cascade controller is evaluated using a simplified prototype of a nonlinearly actuated biped robot in double support placed on top of a one-degree-of-freedom mobile platform and subjected to external disturbances. The achieved experimental results have revealed that the simplified prototype is successfully stabilized.
Morph: A Desktop-Class Humanoid Capable of Acrobatic Behavior
Authors: Tawara Tetsuo , Okumura Yu , Furuta Takayuki , Shimizu Masaharu , Shimomura Masaki , Endo Ken , Kitano Hiroaki
Published: September 2004

A desktop class humanoid robot, morph3, developed for humanoid robotics is described. Consideration to body form is given in order to appeal to a general audience. 138 sensors such as accelerometers, rate gyros, pressure sensors, and force sensors are mounted on morph3. We describe the electrical network which is utilized on-board the humanoid body, and describe some advantages of the system. Actual dynamical behavior such as walking, turning, and motions using the whole-body is performed on the humanoid robot.
Parameter inversion and angle migration in anisotropic elastic media
Authors: Ursin Bjørn
Published: September 2004

Seismic parameter inversion using the inverse generalized Radon transform (GRT) was originally formulated as an integral over source and receiver surface coordinates, involving a Jacobian from angle to surface coordinates. By formulating the inversion directly in terms of angle coordinates at the subsurface image point, I obtain simplified inversion formulas for point scatterers and subsurface reflectors. Amplitude‐preserving angle migration based on the inverse GRT gives an estimate of the scattering coefficient in the Born integral as a function of scattering angle and azimuth. The scattering coefficient is directly related to the linearized plane‐wave reflection coefficient between two anisotropic media, which limits the result to small angles and small contrasts in the elastic parameters. I use the Kirchhoff modeling integral for anisotropic media to formulate a Kirchhoff angle‐migration integral that is valid for large angles and large parameter contrasts. It gives an estimate of the plane‐wave reflection coefficient normalized with respect to amplitude. The Kirchhoff integrals, however, are non reciprocal, so I propose to use new reciprocal integrals for modeling and angle migration. The new migration integral, which is much simpler than the Kirchhoff integral, gives an estimate of the plane‐wave reflection coefficient normalized with respect to the energy flux normal to the reflector. A restricted inverse GRT has been proposed for migration‐velocity analysis. By simplifying this, I derive an expression for amplitude‐compensated migration that is the estimated reflection coefficient divided by the norm of the radiation pattern vector. This partly removes the effects of amplitude variations with scattering angle and azimuth.