bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell cycle related proteins as prognostic parameters in radically resected non-small cell lung cancer
Authors: Esposito V , Baldi A , De Luca A , Tonini G , Vincenzi B , Santini D , Persichetti P , Mancini A , Citro G , Baldi F , Groeger A M , Caputi M 
Published: June 2005

Background:Experimental evidence suggests that lung cancer development and progression can be linked to an increased proliferation rate.Aims/Methods:To evaluate the immunohistochemical expression of seven components of the cell cycle machinery in a series of well characterised non-small cell lung cancer (NSCLC) specimens (n  =  105).Results:Multivariate analysis revealed that simultaneous loss of expression of three of these factors—cyclin D1, the cyclin dependent kinase inhibitor p16, and the tumour suppressor retinoblastoma protein Rb2/p130—correlated with survival, confirming the hypothesis that the cyclin D1–p16–retinoblastoma tumour suppressor pathway is inactivated in most lung cancer samples.Conclusions:These results suggest that loss of control of cell cycle checkpoints is a common occurrence in lung cancer and support the idea that functional cooperation between different cell cycle regulatory proteins constitutes another level of regulation in cell growth control and tumour suppression.
Autofluorescence characterisation of isolated whole crypts and primary cultured human epithelial cells from normal, hyperplastic, and adenomatous colonic mucosa
Authors: DaCosta R S , Andersson H , Cirocco M , Marcon N E , Wilson B C 
Published: June 2005

Background/Aims:In vivo autofluorescence endoscopic imaging and spectroscopy have been used to detect and differentiate benign (hyperplastic) and preneoplastic (adenomatous) colonic lesions. This fluorescence is composed of contributions from the epithelium, lamina propria, and submucosa. Because epithelial autofluorescence in normal and diseased tissues is poorly understood, this was the focus of the present study.Methods:Whole colonic crypts were isolated, and short term primary cultures of epithelial cells were established from biopsies of normal, hyperplastic, and adenomatous colon. Autofluorescence (488 nm excitation) was examined by confocal fluorescence microscopy. Fluorescently labelled organelle probes and transmission electron microscopy were used to identify subcellular sources of fluorescence.Results:Mitochondria and lysosomes were identified as the main intracellular fluorescent components in all cell types. Normal and hyperplastic epithelial cells were weakly autofluorescent and had similar numbers of mitochondria and lysosomes, whereas adenomatous (dysplastic) epithelial cells showed much higher autofluorescence, and numerous highly autofluorescent lysosomal (lipofuscin) granules.Conclusions:Short term primary cell cultures from endoscopic biopsies provide a novel model to understand differences in colonic tissue autofluorescence at the glandular (crypt) and cellular levels. The differences between normal, hyperplastic, and adenomatous epithelial cells are attributed in part to differences in the intrinsic numbers of mitochondria and lysosomes. This suggests that the detection of colonic epithelial fluorescence alone, if possible, may be sufficient to differentiate benign (hyperplastic) from preneoplastic and neoplastic (adenomatous) colonic intramucosal lesions during in vivo fluorescence endoscopy. Furthermore, highly orange/red autofluorescent intracellular granules found only in dysplastic epithelial cells may serve as a potential biomarker.
Immunocytochemical detection of deoxycytidine kinase in haematological malignancies and solid tumours
Authors: Hubeek I , Peters G J , Broekhuizen A J F , Talianidis I , Sigmond J , Gibson B E S , Creutzig U , Giaccone G , Kaspers G J L 
Published: June 2005

Background:Deoxycytidine kinase (dCK) is responsible for the activation of several clinically important deoxynucleoside analogues used for the treatment of haematological and solid malignancies.Aim:To measure dCK expression in tumour cells from different origins.Method:A rabbit antihuman dCK antibody was used for the immunocytochemical detection of dCK expression in three leukaemic cell lines (HL60, U937, and CCRF-CEM) and 97 patient samples (paediatric acute myeloid leukaemia (AML) and lymphoid leukaemia (ALL), retinoblastoma, paediatric brain tumours, and adult non-small cell lung cancer (NSCLC)).Results:CCRF-CEM, U937, and HL60 cells stained positively for dCK and the degree of expression correlated with dCK activity. dCK expression varied between tumour types and between individual patients within one tumour type. dCK was located predominantly in the cytoplasm. The staining intensity was scored as negative (0), low (1+), intermediate (2+), or high (3+). Expression of dCK was high in AML blasts. In contrast, brain tumour samples expressed low amounts of dCK. dCK staining ranged from low (1+) to high (3+) in ALL blasts, retinoblastoma, and NSCLC tissue samples. Staining was consistent (interobserver variability, 88%; κ  =  0.83) and specific. Western blotting detected the dCK protein appropriately at 30 kDa, without additional bands.Conclusions:Immunocytochemistry is an effective and reliable method for determining the expression of dCK in patient samples and requires little tumour material. This method enables large scale screening of dCK expression in tumour samples.
Polymorphism of the 5′ flanking region of the IL-12 receptor β2 gene partially determines the clinical types of leprosy through impaired transcriptional activity
Authors: Ohyama H , Ogata K , Takeuchi K , Namisato M , Fukutomi Y , Nishimura F , Naruishi H , Ohira T , Hashimoto K , Liu T , Suzuki M , Uemura Y , Matsushita S 
Published: June 2005

Background:Individual differences in T cell responsiveness to interleukin 12 (IL-12), resulting from inherited factors, may be responsible for differences in the intensity of cell mediated immune (CMI) responses in patients with leprosy, a disease with a wide clinical spectrum.Aim:Polymorphisms in the 5′ flanking region of the IL12RB2 gene were analysed to determine potential immunogenetic factors affecting CMI responses, using leprosy as a model.Methods:Polymorphisms in the 5′ flanking region of IL12RB2 were examined using direct sequencing techniques, and allele frequencies between patients with lepromatous leprosy and patients with tuberculoid leprosy were compared. The effect of these single nucleotide polymorphisms (SNPs) on IL12RB2 expression was estimated using the dual luciferase reporter gene assay in Jurkat T cells.Results:Several SNPs, including −1035A>G, −1023A>G, −650delG, and −465A>G, were detected within the 5′ flanking region of IL12RB2. The frequency of haplotype 1 (−1035A, −1023A, −650G, −464A) was high in the general Japanese population, but was significantly lower in lepromatous patients compared with tuberculoid patients and healthy controls. Reporter gene assays using Jurkat T cells revealed that all haplotypes carrying one or more SNP exhibited a lower transcriptional activity compared with haplotype 1.Conclusion:SNPs within the 5′ flanking region of IL12RB2 affect the degree of expression of this gene and may be implicated in individual differences in CMI responsiveness to mycobacterial antigens, leading to lepromatous or tuberculoid leprosy.
Survivability of vancomycin resistant enterococci and fitness cost of vancomycin resistance acquisition
Authors: Ramadhan A A , Hegedus E 
Published: June 2005

Aims:To investigate the survivability of vancomycin resistant enterococci (VRE) under dry starvation conditions and the fitness cost of vancomycin resistance.Methods:VRE colonies on cotton swabs were incubated at room temperature in a sterile box and cultured weekly until cultures no longer showed growth. Negative swabs inoculated into brain heart infusion (BHI) broth were subcultured to blood agar after 24, 48, and 72 hours of incubation to resuscitate viable but non-culturable cells. Stability of the vancomycin resistance determinant and of the DNA fingerprint pattern was determined by multiplex polymerase chain reaction (PCR) and repetitive PCR, respectively. Tests for fitness cost were carried out on the same VRE isolates and 28 hospital vancomycin sensitive enterococci (VSE) isolates by incubation and measurement of optical density using a microplate reader and comparing maximum growth rate and lag phase duration between VRE and VSE, using independent samplest tests.Results:Mean maximum time of recovery by primary culture was 8.5 weeks forEnterococcus faecalisVRE and 21.8 weeks forE faeciumVRE. Two of twoE faecalisisolates were resuscitated after 24 hours in BHI broth, and two of fiveE faeciumisolates after 72 hours. No fitness cost of vancomycin resistance was demonstrated.Conclusions:VRE can survive for prolonged periods in a dry starvation state, retaining their genetic complement, including vancomycin resistance determinants, and show little or no fitness cost of vancomycin resistance. Thus, the rate of entry required for VRE to become, and remain, endemic in the community is relatively small.
Biofilm formation and esp gene carriage in enterococci: Table 1
Authors: Ramadhan A A , Hegedus E 
Published: June 2005

Aims:To investigate biofilm production and esp carriage in enterococci.Methods:Biofilm production in vancomycin resistant enterococci (VRE) and vancomycin susceptible enterococci (VSE) was tested on a microtitre plate method, using both brain heart infusion (BHI) broth and human serum as media. Isolates were screened for the esp gene, which has been reported to be essential for biofilm formation in enterococci, by means of the polymerase chain reaction.Results:None of seven VRE and nine of 28 VSE tested formed a biofilm. One initially negative VREEnterococcus faeciumisolate produced a strong biofilm after 21 weeks of dry starvation on a cotton swab. By Fisher’s exact test, there was no significant difference in biofilm formation between VRE and VSE,E faecalisandE faecium, or isolates from different sites. Biofilm formation was independent of possession of the esp gene. One isolate produced a strong biofilm in human serum but only a weak biofilm in BHI, whereas another produced a moderate biofilm in human serum but a weak biofilm in BHI.Conclusions:The acquisition of vancomycin resistance may result in a lower ability to form biofilms, but a larger study using clinical isolates is needed to test this hypothesis. That one initially negative VRE isolate produced a strong biofilm after prolonged dry starvation suggests that biofilm formation may be an adaptive response. The esp gene does not appear to be necessary or sufficient for production of biofilms in enterococci.
The presence of benign prostatic glandular tissue at surgical margins does not predict PSA recurrence
Authors: Kernek K M , Koch M O , Daggy J K , Juliar B E , Cheng L 
Published: June 2005

Background:Serum prostate specific antigen (PSA) increases after radical prostatectomy are thought to indicate recurrent disease, although some suggest they result from benign prostatic epithelial tissue left at surgical margins.Aims:To investigate whether presence, location, and extent of benign prostatic tissue at radical prostatectomy surgical margins influence patient outcome.Methods:One hundred and ninety nine patients with prostate cancer and negative surgical margins were studied. The prostectomy specimens were totally embedded using the whole mount technique. The apex and bladder neck, dissected as a cone from the specimen, were serially sectioned. The total length of benign prostatic tissue at the margins, measured for each location using an ocular micrometer, was obtained by summing the length of all positive sites. The presence, anatomical location, and extent of benign prostatic tissue at the margin were correlated with clinicopathological characteristics and postoperative PSA increases.Results:Fifty five cases had benign prostatic glandular tissue at the surgical margin. The mean length was 2.19 mm (0.1–14.7). The most frequent location of benign prostatic tissue was the apex (40 patients). Presence, anatomical location, and length of benign prostatic tissue at the margin were not significantly associated with age, preoperative PSA, prostate weight, pathological stage, tumour volume, largest tumour dimension, Gleason score, extraprostatic extension, seminal vesical invasion, tumour multifocality, perineural invasion, or PSA recurrence.Conclusions:Benign prostatic tissue was frequently found in margins of apex and bladder base, but uncommon in the anterior or posterior prostate. The presence of benign prostatic tissue at surgical margins had no prognostic relevance.
Cytokeratin phenotyping does not help in distinguishing oesophageal adenocarcinoma from cancer of the gastric cardia
Authors: van Lier M G F , Bomhof F J , Leendertse I , Flens M , Balk A T , Loffeld R J L F 
Published: June 2005

Background:It is sometimes difficult to distinguish between cardia cancer and oesophageal cancer.Aims:To evaluate whether cytokeratin (CK) expression of the tumour can be of value in differentiating between the two tumour types.Methods:Consecutive patients with a malignant tumour in the oesophagus or stomach were recruited. Biopsy specimens were taken for routine haematoxylin and eosin staining. One tissue block with representative tissue was selected for immunohistochemical staining (CK7 and CK20).Results:Endoscopically located adenocarcinoma of the oesophagus was present in 84 patients (64 men, 20 women; mean age, 68 years; range, 44–91). Cancer located primarily in the gastric cardia was present in 63 patients (42 men, 21 women; mean age, 68 years; range, 42–88). The histological diagnosis was metastasis from a primary tumour outside the oesophagus or stomach in 19 patients. The patients were divided into three groups for the immunohistochemical analysis. Patients in group A had definite oesophageal cancer, group B patients had a definite carcinoma located in the gastric cardia, and group C patients had an obstructing tumour distal in the oesophagus at the level of the diaphragm, which could not be passed with the endoscope. Paraffin wax embedded material was available from 122 patients for immunostaining and CK analysis. There was no significant difference in expression or distribution of CK7 or CK20 in the three groups of patients.Conclusion:CK phenotyping cannot distinguish between cancer arising from a Barrett’s oesophagus and carcinoma originating in the gastric cardia.
No GIST-type c-kit gain of function mutations in neuroblastic tumours
Authors: Korja M , Finne J , Salmi T T , Haapasalo H , Tanner M , Isola J 
Published: June 2005

Aims:Neuroblastic tumours (NTs) have been shown to respond to imatinib treatment in vivo and in vitro, possibly via inactivating the c-kit receptor. The purpose of this study was to identify gastrointestinal stromal tumour (GIST)-type c-kit gene associated mutations in exons 9, 11, 13, and 17 in NTs to recognise a subset of tumours that would probably respond to imatinib treatment.Methods:Expression of the c-kit protein was detected immunohistochemically in a total of 37 archival paraffin wax embedded NTs using polyclonal rabbit antihuman c-kit antibody. After immunohistochemistry, c-kit gene associated chromosomal mutations in all cases of NT were detected with denaturing high performance liquid chromatography (HPLC).Results:Denaturing HLPC analysis did not reveal GIST-type mutations in four immunohistochemically detected c-kit positive or in 33 c-kit negative NTs.Conclusions:c-kit receptor expression and GIST-type c-kit gene mutations are rare events in NTs. Oncogenic activation of c-kit in NTs presumably differs from that of GISTs, which may influence their responsiveness to imatinib treatment. Whether c-kit has an essential role in the pathogenesis of NTs remains to be investigated.
Antibiotic selection patterns in acutely febrile new outpatients with or without immediate testing for C reactive protein and leucocyte count
Authors: Takemura Y , Ebisawa K , Kakoi H , Saitoh H , Kure H , Ishida H , Kure M 
Published: June 2005

Background:Excessive use of broad spectrum antibiotics is related to the spread of drug resistant bacterial strains in the community.Aim/methods:The effects of immediate testing for C reactive protein (CRP) and white blood cell count (WBC) on physicians’ choices of antibiotic was investigated in patients with acute infection. Acutely febrile new outpatients were randomised into two groups: group 1 (147 patients) underwent CRP and WBC testing before initial consultation (advance testing). Prescriptions were compared with those in group 2 (no advance testing; 154 patients).Results:In non-pneumonic acute respiratory tract infections, 61 (58%) and 122 (91%) of group 1 and 2 patients were prescribed antibiotics, respectively. Cefcapene pivoxil (third generation cephalosporin) and amoxicillin were the most frequently chosen drugs for group 1 and 2, respectively. Total prescriptions of newer, extended spectrum antibiotics (cefcapene pivoxil and clarithromycin (advanced macrolide)) were reduced by 25% in group 1, although they increased in rate (41 (67%)v55 (45%) prescriptions) because of the decreased prescription of amoxicillin. In group 1, cefcapene pivoxil was preferentially selected when WBC values were greater than 9 × 109/litre. Prescription shifted to macrolides (mainly clarithromycin) in patients without leucocytosis. Patient treatment outcome did not significantly differ between the two groups.Conclusions:The availability of CRP and WBC data during initial consultation greatly reduced prescription of amoxicillin, but had a lesser effect on newer, potent, broad spectrum antibiotics.
Metaplastic breast carcinomas are negative for Her-2 but frequently express EGFR (Her-1): potential relevance to adjuvant treatment with EGFR tyrosine kinase inhibitors?
Authors: Leibl S , Moinfar F 
Published: June 2005

Background:Metaplastic carcinomas (MCs) of the breast rarely express steroid receptors and Her-2, which minimises the options for adjuvant treatment in patients with advanced disease.Aims:To investigate the possible eligibility of patients with MCs for epidermal growth factor receptor (EGFR) targeted treatment.Methods:Immunohistochemical assessment of the expression of steroid receptors and four members of the EGFR/Her family (EGFR/Her-1–4) in 20 MCs (eight with heterologous elements, seven spindle cell MCs, four carcinosarcomas, and one matrix producing carcinoma). Fourteen of the 20 MCs were positive for EGFR (Her-1). Among these cases, 1+, 2+, and 3+ reactivity were seen in two, four, and eight cases, respectively. Her-2 was only present in one MC with 1+ reactivity. Her-3 (1+ reactivity), Her-4 (2+ reactivity), and the androgen receptor (2+ reactivity) were also expressed by one tumour. Oestrogen and progesterone receptors (3+ reactivity each) were detected in the epithelial component only of two carcinosarcoma-type MCs.Conclusions:MCs express EGFR considerably more frequently than the types of breast carcinomas that have been investigated previously. Although molecular analyses for possible genetic alterations in the EGFR might be required, these results suggest that women suffering from this aggressive form of breast carcinoma might benefit from treatment with protein kinase inhibitors, such as gefitinib.
Pathological diagnosis of columnar cell lesions of the breast: are there issues of reproducibility?
Authors: Tan P H , Ho B C-S , Selvarajan S , Yap W M , Hanby A 
Published: June 2005

Aims:To assess inter/intraobserver variability in the interpretation of a series of digitised images of columnar cell lesions (CCLs) of the breast.Methods:After a tutorial on breast CCL, 39 images were presented to seven staff pathologists, who were instructed to categorise the lesions as follows: 0, no columnar cell change (CCC) or ductal carcinoma in situ (DCIS); 1, CCC; 2, columnar cell hyperplasia; 3, CCC with architectural atypia; 4, CCC with cytological atypia; 5, DCIS. Concordance with the tutor’s diagnosis and degree of agreement among pathologists for each image were determined. The same set of images was re-presented to the pathologists one week later, their diagnoses collated, and inter/intraobservor reproducibility and level of agreement for individual images analysed.Results:Diagnostic reproducibility with the tutor ranged from moderate to substantial (κ values, 0.439–0.697) in the first exercise. At repeat evaluation, intraobserver agreement was fair to perfect (κ values, 0.271–0.832), whereas concordance with the tutor varied from fair to substantial (κ values, 0.334–0.669). There was unanimous agreement on more images during the second exercise, mainly because of agreement on the diagnosis of DCIS. The lowest agreement was seen for CCC with cytological atypia.Conclusions:Interobserver and intraobserver agreement is good for DCIS, but more effort is needed to improve diagnostic consistency in the category of CCC with cytological atypia. Continued awareness and study of these lesions are necessary to enhance recognition and understanding.
NONCOMMUTATIVITY IN MAXWELL–CHERN–SIMONS-MATTER THEORY SIMULATES PAULI MAGNETIC COUPLING
Authors: GHOSH SUBIR 
Published: June 2005

We study interactions between like charges in the noncommutative Maxwell–Chern–Simons electrodynamics minimally coupled to spinors or scalars. We demonstrate that the nonrelativistic potential profiles, for only spatial noncommutativity, are nearly identical to the ones generated by a non-minimal Pauli magnetic coupling, originally introduced by Stern.12 Although the Pauli term has crucial roles in the context of physically relevant objects such as anyons and like-charge bound states (or "Cooper pairs"), its inception12 (see also Ref. 13) was ad hoc and phenomenological in nature. On the other hand, we recover similar results by extending the minimal model to the noncommutative plane, which has developed into an important generalization to ordinary spacetime in recent years. No additional input is needed besides the noncommutativity parameter. We prove a novel result that for complex scalar matter sector, the bound states (or "Cooper pairs") can be generated only if the Maxwell–Chern–Simons-scalar theory is embedded in noncommutative spacetime. This is all the more interesting since the Chern–Simons term does not directly contribute a noncommutative correction term in the action.
DOUBLET GROUPS, EXTENDED LIE ALGEBRAS, AND WELL DEFINED GAUGE THEORIES FOR THE TWO-FORM FIELD
Authors: CANTCHEFF MARCELO BOTTA 
Published: June 2005

We propose a symmetry law for a doublet of different form fields, which resembles gauge transformations for matter fields. This may be done for general Lie groups, resulting in an extension of Lie algebras and group manifolds. It is also shown that nonassociative algebras naturally appear in this formalism, which are briefly discussed. Afterwards, a general connection which includes a two-form field is settled-down, solving the problem of setting a gauge theory for the Kalb–Ramond field for generical groups. Topological Chern–Simons theories can also be defined in four dimensions, and this approach clarifies their relation to the so-called B ∧ F theories. We also revise some standard aspects of Kalb–Ramond theories in view of these new perspectives. Since this gauge connection is built upon a pair of fields consisting of a one-form and a two-form, one may define Yang–Mills theories as usually and, remarkably, also minimal coupling with bosonic matter, where the Kalb–Ramond field appears naturally as mediator; so, a new associated conserved charge can be defined. For the Abelian case, we explicitly construct the minimal interaction between B-field and matter following a "gauge principle" and find a novel conserved tensor current. This is our most significative result from the physical viewpoint. This framework is also generalized in such a way that any p-rank tensor may be formulated as a gauge field.