bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deregulated Bag‐1 protein expression in human oral squamous cell carcinomas and lymph node metastases
Authors: Hague Angela , Packham Graham , Huntley Suzanne , Shefford Kathryn , Eveson John W. 
Published: October 2002

AbstractBag‐1 is an anti‐apoptotic protein that promotes metastasis in some tumour cell types. To determine whether Bag‐1 expression is altered in 64 oral squamous cell carcinomas, tumour samples were compared with 17 samples of normal oral epithelium. Normal oral epithelia had pronounced nuclear staining in the basal and maturation layers and weak cytoplasmic staining that was most pronounced in the basal and suprabasal layers. Oral squamous cell carcinomas demonstrated a tendency for reduced nuclear staining intensity (p=0.036). Cytoplasmic staining intensity was not significantly different between tumour and normal tissue. However, many tumours were observed to have less of a difference between nuclear staining intensity and cytoplasmic staining intensity than normal oral epithelium. Furthermore, in lymph node metastases, cytoplasmic Bag‐1 staining was stronger in 8/13 cases than in corresponding primary tumours (p=0.021). Western blotting using nine oral primary carcinoma cell lines and four normal keratinocyte cultures showed that the isoforms Bag‐1S, Bag‐1M, and Bag‐1L were expressed in normal and malignant oral epithelial cells. Bag‐1L unique sequences were shown to adopt an exclusively nuclear, and predominantly nucleolar, localization by use of transiently transfected N‐terminal Bag‐1L‐EGFP. However, levels of Bag‐1L in carcinoma cells did not differ significantly from those of normal keratinocytes. Therefore the reduced nuclear staining observed in oral squamous cell carcinomas compared with normal epithelium may reflect changes in the localization of Bag‐1 isoforms, rather than decreased expression of Bag‐1L. Alterations in the relative proportions of Bag‐1S, Bag‐1M, and Bag‐1L were detected in 6/9 oral carcinoma cell lines; 5/9 oral carcinoma cell lines had a significantly greater proportion of Bag‐1M than normal keratinocytes and in another cell line, Bag‐1L was significantly underrepresented. Overall, the results suggest that Bag‐1 deregulation plays a role in oral carcinogenesis at two different stages: during primary carcinoma development and during lymph node metastasis. Copyright © 2002 John Wiley & Sons, Ltd.
Mucin expression in the ileoanal reservoir reflects incomplete mucosal adaptation
Authors: Sylvester Paul A. , Wong Newton A. C. S. , Myerscough Neil , Warren Bryan F. , Corfield Anthony P. , Thomas Michael G. , Durdey Paul 
Published: October 2002

AbstractRestorative proctocolectomy is regarded as a standard surgical procedure for patients who require a proctocolectomy for ulcerative colitis and familial adenomatous polyposis. The ileal mucosa undergoes colonic phenotypic change with time, but the extent and relevance of these changes to the long‐term safety of the ileoanal pouch are unclear. The aim of this study was to study the mucin biology of this adaptive process in order to assess its extent and possible impact on pouch safety. Ileoanal pouch biopsies from a cohort of patients and normal ileal and colonic controls were subjected to histological, biochemical, histochemical, and immunohistochemical mucin analysis. Mucin sulphation and sialic acid O‐acetylation were studied as parameters of colonic phenotypic change. Fifty‐one patients, 16 ileal, and 22 colonic controls were studied. Seventy percent of biopsies retained villous mucosal architecture, with no cases of dysplasia detected. Ileoanal pouch mucosal sulphation and sialic acid O‐acetylation did not reach colonic levels, thus indicating limited evidence for a more colonic phenotype. The data from this study suggest that colonic phenotypic change within the ileoanal reservoir is incomplete, with no cases of dysplasia detected. The degree of phenotypic change is less than in previous studies, which may support, butnot prove, our hypothesis that there may be a process of reversion to an ileal type mucosa in the ileoanal reservoir with time. Copyright © 2002 John Wiley & Sons, Ltd.
Short‐term rhythmic proliferation of human breast cancer cell lines: surface effects and fractal growth patterns
Authors: Sedivy Roland , Thurner Stefan , Budinsky Alexandra C. , Köstler Wolfgang J. , Zielinski Christoph C. 
Published: October 2002

AbstractKinetic studies of cell proliferation rates shed light on the growth dynamics of cancer. Most such studies are based on measurements of cell numbers that were evaluated in time intervals of about 12 h. Studies of the initial tumour growth with short measuring intervals are rare. This study was therefore designed with 1 h measuring intervals over a 24 h period. Human breast cancer cell lines (ZR‐75‐1, SK‐BR‐3, MCF‐7) and a benign cell line (HBL‐100) were used to study the hourly thymidine uptake as a measure of cells in synthesis. In parallel experiments, the same cell lines were also exposed to tumour necrosis factor alpha (TNF‐α) to explore the effect of an apoptosis‐inducing substance on initial tumour growth kinetics. In time‐evolution plots, there was an oscillation of the labelling index of thymidine uptake for all investigated cell lines, with and without TNF‐α. Based on the results obtained, a mathematical model was developed mimicking the real experiment. To describe the system dynamically a cellular automaton model was studied. The growth kinetics revealed by the simulation were in accordance with our experimental data. Two‐ and three‐dimensional growth simulations of this computer model yielded objects morphologically similar to real images of human breast cancer. Almost identical fractal dimensions of the virtual and real tumours further supported this visual similarity. The cellular automata models could, therefore, be seen as a bridge towards realistic in vivo scenarios. From a clinical point of view, the results obtained may be applicable not only to primary tumours, but even to tumour cell microfoci and small metastases, which are a major concern in early metastasizing tumours such as breast cancer. Copyright © 2002 John Wiley & Sons, Ltd.
Expression of carbonic anhydrase IX in breast is associated with malignant tissues and is related to overexpression of c‐erbB2
Authors: Bartošová Mária , Parkkila Seppo , Pohlodek Kamil , Karttunen Tuomo J. , Galbavý Štefan , Mucha Vojtech , Harris Adrian L. , Pastorek Jaromír , Pastoreková Silvia 
Published: October 2002

AbstractCA IX is a tumour‐associated carbonic anhydrase with proposed roles in pH modulation and intercellular communication. Its distribution was examined in normal, benign and malignant breast tissues and compared with expression of breast tumour markers including oestrogen receptor, c‐erbB2, c‐erbB3 and CD44. Tissue specimens were analysed using immunohistochemistry and/or reverse transcriptase–polymerase chain reaction (RT‐PCR). CA IX was detected by IHC in 12/26 (46%) malignant tissues, 4/36 (11%) benign lesions, but not in 10 normal breasts. Staining was mostly confined to plasma membranes of abnormal epithelial cells, but in five cases was found in adjacent stroma. Semi‐quantitative RT‐PCR detected CA9 mRNA in 25/39 (64%) malignant tumours, 11/33 (33%) benign lesions, but in none of three normal breasts. Comparative RT‐PCR analysis of malignant tissues revealed a relationship between CA9 positivity and c‐erbB2 overexpression (p=0.05). Moreover, CA9‐positive specimens displayed a significantly higher median level of c‐erbB2 than CA9‐negative ones (p=0.02). No significant association was found with the other markers. The results of this study support the possible importance of CA IX for breast carcinogenesis and suggest its potential use as a breast tumour marker. Copyright © 2002 John Wiley & Sons, Ltd.
Tenascin‐C is a useful marker for disease activity in myocarditis
Authors: Imanaka‐Yoshida Kyoko , Hiroe Michiaki , Yasutomi Yasuhiro , Toyozaki Tetsuya , Tsuchiya Takuro , Noda Naomi , Maki Toshiki , Nishikawa Toshio , Sakakura Teruyo , Yoshida Toshimichi 
Published: October 2002

AbstractTenascin‐C (TNC) is an extracellular matrix protein which appears at active sites of tissue remodelling during embryogenesis or cancer invasion. In normal heart, TNC is only present during the early stages of development but reappears in pathological states. This study examined the diagnostic value of TNC for assessing disease activity of myocarditis. Expression of TNC was examined in myosin‐induced autoimmune myocarditis mouse models. Sequential changes in amount, localization and the producing cells were analysed by reverse transcriptase–polymerase chain reaction, western blotting, immunohistochemistry and in situ hybridization and compared with the histological picture. The expression of TNC was upregulated at a very early stage of myocarditis. Immunostaining was detectable before cell infiltration and myocytolysis became histologically apparent, remained during the active stage while cell infiltration and necrosis continued, and disappeared in scar tissue with healing. TNC immunostaining was always observed at the periphery of necrotic or degenerating cardiomyocytes in foci of inflammation, the expression level correlating with histological evidence of inflammatory activity. Interstitial fibroblasts were the major source of TNC, expressing the large isoform containing alternative splicing sites. These data demonstrate that TNC is a useful marker for evaluation of disease activity in myocarditis. Copyright © 2002 John Wiley & Sons, Ltd.
Multiple complementary transcripts of pCMa1, a novel gene located at chromosome 11p15.1–2, and melanocytic cell transformation
Authors: Meije Clifton B. , Das Pranab K. , Jans Miranda M. E. , Hau Chi , van der Wal Allard C. , Alders Marielle , Hakvoort Theodorus B. M. , Weidle Ulrich H. , Lamers Wouter H. , Swart Guido W. M. 
Published: October 2002

AbstractThe cDNA clone pCMa1 (0.45 kb) is one of the 12 novel cDNAs, previously identified when comparing RNA expression profiles of melanocytes, naevus cells, and non‐metastatic melanoma cells. This clone did not reveal a unique long open reading frame. The pCMa1 gene localized to the distal, telomere proximal region on the short arm of chromosome 11.p15.1–2. Northern blot analyses with single‐stranded cRNA probes revealed the presence of various complementary pCMa1 transcripts of different lengths, which are not enriched in the poly(A)+ RNA fraction. The arbitrarily defined plus strand (used as a probe) mainly hybridized to 0.45 kb and 4.0 kb minus transcripts in total RNA samples, and the minus strand (used as a probe) hybridized to a major plus transcript of 4.0 kb. By RNA in situ hybridization, the highest levels of the plus transcripts were observed in melanocytic naevi (12/12), particularly in congenital naevi, whereas normal skin melanocytes (12/12) were negative. pCMa1 plus transcripts were detected in naevus cell nests (100%) near the dermo‐epidermal junction. Expression, however, diminished to some extent in the deeper parts of the melanocytic naevi. Although most of the cutaneous primary melanoma lesions (11/15) showed detectable, but variable levels of plus transcripts of pCMa1 in the papillary to reticular dermis, not more than 10% of the melanoma cells were positive. The majority of melanoma metastases (6/7) were negative, while the positive lesion originated from a patient with a positive primary melanoma. Furthermore, plus transcripts were present in the nuclei of non‐metastatic melanoma cells in culture, whereas metastatic cells showed elevated expression both in the nucleus and in the cytoplasm. Briefly, the data show transient up‐regulation of pCMa1 in neoplastic progression of melanocytic cells, with peak levels occurring during naevus stages, and suggest that pCMa1 is a molecular marker in melanocytes for the early changes from the proliferating phenotype to malignant transformation. Copyright © 2002 John Wiley & Sons, Ltd.
Epidermal stem cells
Authors: Janes Sam M. , Lowell Sally , Hutter Caroline 
Published: October 2002

AbstractThe clinical implications of understanding epidermal stem cell biology abound. Thousands of burns victims across the world have benefited from early research into the proliferation of epidermal keratinocytes in vitro. Advances now indicate there are a number of stem cell repositories within the epidermis, two of which, the interfollicular epidermis and the bulge region of the hair follicle, may supply each other when damaged. This review details the progress made in the identification and characterisation of stem cells within the epidermis and discusses the molecules involved in the epidermal stem cell's choice of fate. Finally, the skin, like bone marrow, could be a readily accessible source of stem cells for therapeutic intervention and evidence of skin stem cell plasticity is highlighted.
Analysis of the progression of fibroepithelial tumours of the breast by PCR‐based clonality assay
Authors: Kuijper Arno , Buerger Horst , Simon Ronald , Schaefer Karl‐Ludwig , Croonen Anita , Boecker Werner , van der Wall Elsken , van Diest Paul J. 
Published: October 2002

AbstractFibroadenoma and phyllodes tumour of the breast are both fibroepithelial tumours. Although progression to epithelial malignancy has been described, the behaviour of most fibroadenomas is benign. Phyllodes tumours, on the other hand, can display locally destructive growth and can even metastasize. A relationship between the two tumours has been suggested in the literature. This study investigated the clonality of both the stroma and the epithelium of these fibroepithelial tumours and attempted to construct a model in which fibroadenoma can progress in both an epithelial and a stromal direction. Fibroadenomas (n=25) and phyllodes tumours (n=12) were selected for analysis. Tissue was microdissected and analysed for clonality using a polymerase chain reaction (PCR)‐based assay targeted at an X‐linked polymorphic marker, the human androgen receptor gene (HUMARA). Nineteen fibroadenomas and nine phyllodes tumours could be analysed. Normal‐appearing epithelium, hyperplastic epithelium, and stroma removed from fibroadenomas were polyclonal. As expected, carcinoma in situ (CIS) removed from four fibroadenomas was monoclonal. Three areas of apparent stromal expansion within fibroadenoma were monoclonal, suggesting stromal progression. Mostly, the stroma of phyllodes tumours was monoclonal and the epithelium polyclonal. In two cases, however, the epithelium seemed to be monoclonal, whereas in three other cases the stromal component was polyclonal. These findings indicate that fibroadenoma can progress in an epithelial direction to CIS and in a stromal direction to phyllodes tumour. Copyright © 2002 John Wiley & Sons, Ltd.
Genetic progression in sporadic endometrial and gastrointestinal cancers with high microsatellite instability
Authors: Furlan Daniela , Casati Barbara , Cerutti Roberta , Facco Carla , Terracciano Luigi , Capella Carlo , Maria Chiaravalli Anna 
Published: October 2002

AbstractThis study selected a series of 136 MSI‐H (microsatellite instability at high frequency) gastric, colorectal, and endometrial carcinomas combining immunohistochemical analysis for hMLH1 or hMSH2 gene products and microsatellite study. The clinico‐pathological profile of all tumours was correlated with the overall instability rates at coding and non‐coding repeats, in order to clarify the role and the mutation timing of seven target genes (TGFβRII, IGFIIR, BAX, hMSH3, hMSH6, CHK1, and BRCA2) in the progression of an MSI‐H neoplasm. Regardless of the primary site, the results confirm a model of oncogenesis in which inactivation of hMLH1, or less frequently hMSH2, may initiate a pathway culminating in a progressive accumulation of frameshifts in coding region (CDR) microsatellites. Comparing gastrointestinal and endometrial tumours, significantly lower levels of microsatellite instability at both coding and non‐coding repeats were observed. Among gastric and colorectal tumours, the detection of small shortening within Bat‐26 and Bat‐25 markers defines a subgroup of MSI‐H gastrointestinal tumours invariably characterized by early stage at diagnosis. In these tumours, mutations of TGFβRII or BAX genes precede frameshifts in the other tested genes. The analysis of correlations between the mutational and clinico‐pathological profiles of advanced gastrointestinal tumours revealed that the higher levels of microsatellite instability at both coding and non‐coding repeats were not associated with a more advanced clinico‐pathological stage or a less favourable outcome. A significant association was observed between a low number of CDR frameshifts and the presence of lymph‐node metastasis in advanced gastrointestinal tumours. The existence of advanced MSI‐H tumours with more aggressive behaviour and a ‘mild mutator phenotype’ could be explained by hypothesizing an overlapping of different mechanisms of tumourigenesis, including both the mutator and the suppressor pathways; this should be tested by further studies. Copyright © 2002 John Wiley & Sons, Ltd.
Potential impact of a new blood glucose monitoring device: the GlucoWatch® Biographer
Authors: Chan NN , Hurel SJ 
Published: October 2002

AbstractHome blood glucose monitoring may be laborious, time‐consuming, inconvenient and painful. Failure to test may preclude optimisation of glycaemic control. We aimed to evaluate the potential usefulness of a new noninvasive automatic glucose monitor, the GlucoWatch® Biographer. Eight patients with type 1 diabetes and two with type 2 diabetes (4M:6F) aged between 23 and 65 years participated in this study. All participants were given 1 hour of instruction prior to provision of the GlucoWatch®. They were given contact numbers and reviewed weekly. Several disadvantages were encountered by the participants, which included the daily 3 hour calibration period (n = 10), skin irritations (n = 6) and skipped measurements (n = 2) due to unsatisfactory probe contact due to skin temperature or sweats. Several patients, however, found it invaluable to have their daily profile monitored to allow insulin dosage adjustment and detection of hypoglycaemia.The GlucoWatch® Biographer is an invaluable tool that allows noninvasive detection of glucose trends, which contributes to glycaemic control. However, it is not suitable for every patient. Self‐motivation and ability to learn how to use the device are the key factors. Copyright © 2002 John Wiley & Sons, Ltd.
Reader beware: diabetes advice on the web
Authors: Kelly William , Connolly Vincent , Bilous Rudolf , Stewart Amanda , Nag Satyajit , Bowes Daniel , Loader Brian , Muncer Steve 
Published: October 2002

AbstractIn recent years there has been a significant expansion of information and advice for people with diabetes available on the Internet. Interestingly much of this is provided by lay people, who often have diabetes themselves. Consequently we decided to critically evaluate the quality of non‐professional advice available on the Internet for people with diabetes. This was undertaken by identifying a dedicated diabetes newsgroup, which was analysed by a panel of specialist diabetologists who assessed the quality of postings and responses using a six point classification. Each message was rated independently by each of the five panel members and scores were compared for reliability of judgement. From the newsgroup used mainly by non‐professionals 61 start messages comprised 54 questions, six statements and one commercial proposition. Sixteen questions related to diet, nine to glycaemic control and blood tests, ten to tablets and insulin, eight to complications, and there were 18 others. 61 start messages were categorised as four excellent, 24 less good—some details, 17 poor—little detail, 17 vague, but none were misleading or incomprehensible. After 5 days 61 messages had generated 242 responses, which were assessed as 13 evidence based excellent, 60 accepted wisdom, 137 personal opinion anecdote, 26 misleading or irrelevant, one false and five open to misinterpretation. There were 146 respondents (30 more than once), range of replies 1–15, identified as a doctor in four instances, but usually patient, relative or unknown. Newsgroups such as the one we analysed are clearly a valuable forum for persons with diabetes to interact with each other, share experiences and provide social support. For the most part the level of understanding about the condition was quite extensive, with the debate being largely technical in nature. Of the 242 responses, only six were regarded as either false or possibly dangerous. This raises important questions about how to ensure that the information provided on the Internet for persons with diabetes is accurate, sensible, evidence based and easily accessible. Copyright © 2002 John Wiley & Sons, Ltd.
An evaluation of diabetic care in registered nursing homes
Authors: Duffy Una , Craig Michael 
Published: October 2002

AbstractThis study examines current clinical practice in relationship to the care of diabetic patients in Registered Nursing Homes in Argyll and Clyde NHS Board and training needs of staff. The prevalence of diabetes was found to be 6.5% (95% CI 4.7–8.3) with 12 having type 1 and 82 having type 2 diabetes. This comprised 58 women and 42 men with a mean age of 79 years. The mean number of patients per home was 2.6 (95% CI 1.9–3.4) with a range of 0–22. Eighty‐one patients were medically cared for solely by general practice. Seventeen homes screened new patients on admission for diabetes using a variety of methods; only six homes tested blood glucose levels as part of their screening programme. Ninety‐one per cent of the sample were receiving regular blood glucose monitoring; of the patients treated with insulin 50% were having blood glucose monitoring a minimum of once per day. Forty‐seven per cent had annual retinopathy screening, with 62% being undertaken by an accredited optometrist. Ninety‐one per cent of patients had been treated by a chiropodist in the previous 12 months. A dietician had assessed 13% of patients in the previous 12 months. There was a positive response to further education on diabetes, with particular needs expressed for staff training, including blood monitoring and screening. This study has formed the basis for the development of nursing guidelines for diabetes in nursing homes and the development of an educational programme. Copyright © 2002 John Wiley & Sons, Ltd.
The need for a national infrastructure to improve the rational use of therapeutics
Authors: Califf Robert M. 
Published: October 2002

AbstractThe current medical care environment has created expectations that exceed its capabilities, one effect of which has been an increasing awareness of lapses in the quality of healthcare, including medical errors. As more new therapies reach clinical application, the expectations on the part of the public are unlikely to lessen, and yet the ability to assure patients that the benefits of these therapies are known, and that they are without serious side‐effects or untoward consequences, eludes the healthcare system. Based on initial experience with a new federal program, the Centers for Education and Research on Therapeutics (CERTs), we propose a national approach to therapeutics education and research, through a public–private partnership that involves academic medical centers, the federal government, industry, and the public. Through a concerted approach, we believe that significant gaps in our understanding of key issues in therapeutics and our ability to educate practitioners, policy makers, and consumers can be significantly enhanced in a manner that could not be achieved without a coordinated approach. Copyright © 2002 John Wiley & Sons, Ltd.