bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gains and losses of adhesion molecules (CD44, E‐cadherin, and β‐catenin) during oral carcinogenesis and tumour progression
Authors: Bánkfalvi Agnes , Kraßort Melanie , Buchwalow Igor B. , Végh Andras , Felszeghy Endre , Piffkó Jozsef 
Published: October 2002

AbstractThe aim of this study was to define whether or not the impaired expression of CD44, E‐cadherin (E‐cad), and β‐catenin (β‐cat) correlates with the clinical evolution and prognosis of oral cancer. Ninety‐three primary oral squamous cell carcinomas (OSCCs) with tumour‐adjacent normal and/or dysplastic mucosa, 30 associated metastases, and 12 recurrences were immunostained for CD44s, ‐v3, ‐v4, ‐v5, ‐v6, ‐v7, ‐v9, E‐cad, and β‐cat. In non‐neoplastic epithelium, all molecules investigated were constitutively expressed in the basal layers. In the majority of dysplasias, immunoreactivity for all adhesion molecules was increased, but there was restricted loss for CD44s, E‐cad, and β‐cat in a few cases. In carcinomas, a striking accumulation of CD44s, v3, v4, v9 and a loss of E‐cad/β‐cat were observed at the invasive tumour front. In metastases and recurrences, besides a loss of CD44s, v4, v7, and E‐cad, a significant increase of v9 was recorded, whereas CD44v5 and v6 remained unchanged. Clinically, reduced expression of CD44v3, E‐cad, and changes of CD44v9 phenotype within the primary tumours correlated significantly with poor prognosis; decreased β‐cat expression was a predictive marker for nodal metastases. These findings indicate that there is some perturbed expression of adhesion molecules during the stepwise course of oral carcinogenesis and tumour progression. Distinct phenotypic alterations project poor prognosis, while others predict metastasis. Some of these restricted molecular changes may serve as potential targets for future antibody‐based tumour therapy. Copyright © 2002 John Wiley & Sons, Ltd.
Therapeutic effect of sulphated hyaluronic acid, a potential selectin‐blocking agent, on experimental progressive mesangial proliferative glomerulonephritis
Authors: Matsuda Mitsuhiro , Shikata Kenichi , Shimizu Fujio , Suzuki Yasuo , Miyasaka Masayuki , Kawachi Hiroshi , Kawashima Hiroto , Wada Jun , Sugimoto Hikaru , Shikata Yasushi , Ogawa Daisuke , Tojo Shinichiro J. , Akima Kazuo , Makino Hirofumi 
Published: October 2002

AbstractThe initial event in the process of leukocyte infiltration is characterized by leukocyte rolling on the surface of the endothelium, which is mediated by selectins. P‐ and L‐selectin bind to the sulphated sugar chains of their natural ligands, including sulphated glycolipids such as sulphatide. Recently, it has been demonstrated that sulphated glycolipids and sulphated oligosaccharides interfere with selectin binding pathways. This study synthesized sulphated hyaluronic acid (SHA), which is a potential selectin‐blocking agent, and examined its therapeutic effect on the experimental progressive mesangial proliferative glomerulonephritis induced by anti‐Thy‐1 monoclonal antibody (1‐22‐3 MAb) after unilateral nephrectomy. The selectin‐inhibitory effect of SHA in vitro was confirmed. SHA inhibited the binding of P‐ and L‐selectin to sulphatide, which is a glycolipid ligand for P‐ and L‐selectin, at a concentration of 1.5 µg/ml and 100 µg/ml. Immunohistochemical examination showed that P‐selectin was up‐regulated in the glomeruli in the 1‐22‐3 MAb nephritis model, while the ligands for L‐selectin were not detected in the glomerular tufts. A single administration of SHA ameliorated proteinuria and glomerular leukocyte infiltration in 24 h after the injection of anti‐Thy‐1 MAb. Anti‐P‐selectin MAb, but not anti‐L‐selectin MAb, inhibited proteinuria and glomerular leukocyte infiltration. To examine further the therapeutic effect of SHA on chronic glomerulonephritis, SHA was administered daily from day 3 to day 14 in this model. Proteinuria and glomerular leukocyte infiltration were significantly diminished in SHA‐treated rats on day 14. These results suggest that SHA ameliorated rat progressive mesangial proliferative glomerulonephritis by inhibiting P‐selectin‐dependent leukocyte infiltration in glomeruli. Sulphated oligosaccharides may be beneficial for the therapy of mesangial proliferative glomerulonephritis. Copyright © 2002 John Wiley & Sons, Ltd.
Alterations of the INK4a‐ARF gene locus in pleomorphic adenoma of the parotid gland
Authors: Weber Anette , Langhanki Larissa , Schütz Alexander , Wittekind Christian , Bootz Friedrich , Tannapfel Andrea 
Published: October 2002

AbstractPleomorphic adenomas of the parotid gland are benign tumours composed of epithelial and mesenchymal cells. The INK4a‐ARF (CDKN2A) locus on chromosome 9p21 encodes two tumour suppressor proteins, p16INK4a and p14ARF, which act as upstream regulators of the Rb‐CDK4 and p53 pathways. To study the contribution of each pathway in pleomorphic adenomas, this study analysed alterations of p14ARF, p16INK4a, p53, and pRb in these tumours. After microdissecting the different histological components, 42 pleomorphic adenomas of the parotid gland were analysed for INK4a‐ARF inactivation by DNA sequence analysis, methylation‐specific PCR (MSP), restriction enzyme‐related polymerase chain reaction (RE‐PCR), mRNA expression, microsatellite analysis, and immunohistochemistry. In addition, microdeletion of p14ARF and p16INK4a were assessed by differential PCR. The status of p53 and Rb was examined by direct sequencing and immunohistochemistry. Using microdissection, it was possible to examine the tumour components, i.e. epithelial, mesenchymal, and transitional, separately after immunohistochemical identification. Methylation of p14ARF was found in 1/42 cases and alterations of p16INK4a occurred in 12/42 of pleomorphic adenomas, which correlated with loss of mRNA transcription. Microdeletions or specific mutations of either exon were not detected. Methylation was detected exclusively in the epithelial and transitional components and not within the mesenchymal part of the tumour. p53 mutations were detected in 4/42 adenomas, also occurring solely in the epithelial components of the tumours. pRb was detected immunohistochemically in 40/42 adenomas. In normal, corresponding parotid tissue, p14ARF, p16INK4a, p53, and pRb alterations were not observed. The observation that alterations of p14ARF and p16INK4a, and also p53 mutations, occurred exclusively in the epithelial and transitional components of pleomorphic adenoma supports the theory that these areas are prone to malignant transformation to carcinoma in adenoma. Copyright © 2002 John Wiley & Sons, Ltd.
Morphometry of dermal collagen orientation by Fourier analysis is superior to multi‐observer assessment
Authors: van Zuijlen Paul PM , de Vries Henry JC , Lamme Evert N , Coppens Joris E , van Marle Jan , Kreis Robert W , Middelkoop Esther 
Published: October 2002

AbstractIn human dermis, collagen bundle architecture appears randomly organized, whereas in pathological conditions, such as scar tissue and connective tissue disorders, collagen bundle architecture is arranged in a more parallel fashion. Histological examination by one or two observers using polarized light is the most common method to determine collagen orientation. The hypothesis on which this study is based is that an objective image analysis technique, Fourier analysis, would improve the reliability (are the measurements reproducible?) and the accuracy (does the method measure what it is supposed to measure?) of collagen orientation assessment, compared with observer ratings. Fourier analysis was applied to 271 images of scar tissue and normal skin that were acquired by confocal laser‐scanning microscopy. Observers rated the same areas using polarized light as well as the confocal microscopy images. Computer images consisting of different types of ellipses were generated with a fixed orientation. Observers and Fourier analysis evaluated the images to evaluate accuracy. The inter‐observer reliability was acceptable when at least three observers rated polarized light images (r > 0.69), whereas two observers were sufficient for rating confocal microscopy images (r > 0.71). Fourier analysis correlated better with observer ratings of confocal microscopy images (r = 0.69) than with polarized light microscopy images (r = 0.42). Fourier analysis was more accurate than four observers for the evaluation of the ‘true’ orientation for almost all types of computer‐generated images. For the first time it is shown that Fourier image analysis is suitable for the morphometry of dermal collagen orientation and leads to a superior measurement of collagen orientation compared with subjective histological evaluation by several experts. If an evaluation is performed by conventional light microscopy, at least three observers are required to attain an acceptable inter‐observer reliability. Copyright © 2002 John Wiley & Sons, Ltd.
Antimicrobial peptides are expressed and produced in healthy and inflamed human synovial membranes
Authors: Paulsen Friedrich , Pufe Thomas , Conradi Lenard , Varoga Deike , Tsokos Michael , Papendieck Jann , Petersen Wolf 
Published: October 2002

AbstractThe objective of this study was to determine the expression and production of antimicrobial peptides by healthy and inflamed human synovial membranes. Deposition of the antimicrobial peptides lysozyme, lactoferrin, secretory phospholipase A2 (sPA2), matrilysin (MMP7), human neutrophil alpha‐defensins 1–3 (HNP 1–3), human beta‐defensin 1 (HBD‐1), and human beta‐defensin 2 (HBD‐2) was determined by immunohistochemistry. Expression of mRNA for the antimicrobial peptides bactericidal permeability‐increasing protein (BPI), heparin binding protein (CAP37), human cationic antimicrobial protein (LL37), human alpha‐defensin 5 (HD5), human alpha‐defensin 6 (HD6), HBD‐1, HBD‐2, and human beta‐defensin 3 (HBD‐3) was analysed by reverse transcription polymerase chain reaction (RT‐PCR). RT‐PCR revealed CAP37 and HBD‐1 mRNA in samples of healthy synovial membrane. Additionally, HBD‐3 and/or LL37 mRNA was detected in synovial membrane samples from patients with pyogenic arthritis (PA), osteoarthritis (OA) or rheumatoid arthritis (RA). BPI, HD5, HD6, and HBD‐2 mRNAs were absent from all samples investigated. Immunohistochemistry identified lysozyme, lactoferrin, sPA2, and MMP7 in type A synoviocytes of all samples. HBD‐1 was only present in type B synoviocytes of some of the samples. Immunoreactive HBD‐2 peptide was only visible in some inflamed samples. HNP1‐3 was detected in both healthy and inflamed synovial membranes. The data suggest that human synovial membranes produce a broad spectrum of antimicrobial peptides. Under inflammatory conditions, the expression pattern changes, with induction of HBD‐3 in PA (LL37 in RA; HBD‐3 and LL37 in OA) as well as down‐regulation of HBD‐1. HBD‐3 holds therapeutic potential in PA as it has a broad spectrum of antimicrobial activity and accelerates epithelial healing. However, caution is appropriate since defensins also promote fibrin formation and cell proliferation — key elements in joint infection. Clarification of the role of antimicrobial peptides in OA and RA will require further investigation. Copyright © 2002 John Wiley & Sons, Ltd.
The framework of pathology: good laboratory practice by quantitative and molecular methods
Authors: Baak Jan PA 
Published: October 2002

AbstractCombined confocal laser scan microscopy (CLSM) and Fourier analysis (FA) by non‐pathologists of dermal collagen bundle orientation recently gave results superior to subjective evaluation by experts. According to Good Laboratory Practice (GLP) criteria, combined CLSM/FA has not yet been adequately tested to replace current collagen evaluation, but this will not take long. Non‐pathologists (clinicians) will then have taken over a laboratory test historically belonging to pathology. A general trend in this direction may develop, because pathologists seem not always to care enough about clinical significance, reproducibility and prognostic value, and new demands for innovative methods. Quantitative image analysis (QIA) and molecular methods are reproducible, inexpensive, and easy to perform; they often have greater value than classical evaluations and their cost–benefit ratio is good. However, their acceptance is not as widespread as one would expect and theoretical reasons which have been advanced do not provide a satisfactory explanation. A formal implementation study was therefore performed, in which an attempt was made to modernize a classical pathology laboratory. An external customer satisfaction investigation showed that 96% of the clinicians were ‘very satisfied’ (the highest rating possible) with the completed innovations, contrasting with low satisfaction at the beginning. Lack of primary innovative leadership among pathologists was judged to be the dominant cause preventing implementation. Pathologists should focus on carefully reacting to new clinical needs, using GLP criteria. Reproducibility and predictive accuracy should be major themes in any pathology practice. Copyright © 2002 John Wiley & Sons, Ltd.
A copula‐based model for multivariate non‐normal longitudinal data: analysis of a dose titration safety study on a new antidepressant
Authors: Lambert Philippe , Vandenhende François 
Published: October 2002

AbstractA new model for multivariate non‐normal longitudinal data is proposed. In a first step, each longitudinal series of data corresponding to a given response is modelled separately using a copula to relate the marginal distributions of the response at each time of observation. In a second step, at each observation time, the conditional (on the past) distributions of each response are related using another copula describing the relationship between the corresponding variables. Note that there is no need to consider the same family of distributions for these response variables. The technique is illustrated in a dose titration safety study on a new antidepressant. The haemodynamic effect on diastolic blood pressure, systolic blood pressure and heart rate is studied. These three responses are measured repeatedly over time on ten healthy volunteers during the dose escalation. The available covariates are sex and the concentration of drug in the plasma at time of measurement. Copyright © 2002 John Wiley & Sons, Ltd.
Proportional hazards models with frailties and random effects
Authors: O'Quigley John , Stare Janez 
Published: October 2002

AbstractWe discuss some of the fundamental concepts underlying the development of frailty and random effects models in survival. One of these fundamental concepts was the idea of a frailty model where each subject has his or her own disposition to failure, their so‐called frailty, additional to any effects we wish to quantify via regression. Although the concept of individual frailty can be of value when thinking about how data arise or when interpreting parameter estimates in the context of a fitted model, we argue that the concept is of limited practical value. Individual random effects (frailties), whenever detected, can be made to disappear by elementary model transformation. In consequence, unless we are to take some model form as unassailable, beyond challenge and carved in stone, and if we are to understand the term ‘frailty’ as referring to individual random effects, then frailty models have no value. Random effects models on the other hand, in which groups of individuals share some common effect, can be used to advantage. Even in this case however, if we are prepared to sacrifice some efficiency, we can avoid complex modelling by using the considerable power already provided by the stratified proportional hazards model. Stratified models and random effects models can both be seen to be particular cases of partially proportional hazards models, a view that gives further insight. The added structure of a random effects model, viewed as a stratified proportional hazards model with some added distributional constraints, will, for group sizes of five or more, provide no more than modest efficiency gains, even when the additional assumptions are exactly true. On the other hand, for moderate to large numbers of very small groups, of sizes two or three, the study of twins being a well known example, the efficiency gains of the random effects model can be far from negligible. For such applications, the case for using random effects models rather than the stratified model is strong. This is especially so in view of the good robustness properties of random effects models. Nonetheless, the simpler analysis, based upon the stratified model, remains valid, albeit making a less efficient use of resources. Copyright © 2002 John Wiley & Sons, Ltd.
A semi‐parametric accelerated failure time cure model
Authors: Li Chin‐Shang , Taylor Jeremy M. G. 
Published: October 2002

AbstractA cure model is a useful approach for analysing failure time data in which some subjects could eventually experience, and others never experience, the event of interest. A cure model has two components: incidence which indicates whether the event could eventually occur and latency which denotes when the event will occur given the subject is susceptible to the event. In this paper, we propose a semi‐parametric cure model in which covariates can affect both the incidence and the latency. A logistic regression model is proposed for the incidence, and the latency is determined by an accelerated failure time regression model with unspecified error distribution. An EM algorithm is developed to fit the model. The procedure is applied to a data set of tonsil cancer patients treated with radiation therapy. Copyright © 2002 John Wiley & Sons, Ltd.
A simple confidence interval for meta‐analysis
Authors: Sidik Kurex , Jonkman Jeffrey N. 
Published: October 2002

AbstractIn the context of a random effects model for meta‐analysis, a number of methods are available to estimate confidence limits for the overall mean effect. A simple and commonly used method is the DerSimonian and Laird approach. This paper discusses an alternative simple approach for constructing the confidence interval, based on the t‐distribution. This approach has improved coverage probability compared to the DerSimonian and Laird method. Moreover, it is easy to calculate, and unlike some methods suggested in the statistical literature, no iterative computation is required. Copyright © 2002 John Wiley & Sons, Ltd.
Parametric models for accelerated and long‐term survival: a comment on proportional hazards
Authors: Frankel Paul , Longmate Jeffrey 
Published: October 2002

AbstractThe Cox proportional hazards model (CPH) is routinely used in clinical trials, but it may encounter serious difficulties with departures from the proportional hazards assumption, even when the departures are not readily detected by commonly used diagnostics. We consider the Gamel–Boag (GB) model, a log‐normal model for accelerated failure in which a proportion of subjects are long‐term survivors. When the CPH model is fit to simulated data generated from this model, the results can range from gross overstatement of the effect size, to a situation where increasing follow‐up may cause a decline in power. We implement a fitting algorithm for the GB model that permits separate covariate effects on the rapidity of early failure and the fraction of long‐term survivors. When effects are detected by both the CPH and GB methods, the attribution of the effect to long‐term or short‐term survival may change the interpretation of the data. We believe these examples motivate more frequent use of parametric survival models in conjunction with the semi‐parametric Cox proportional hazards model. Copyright © 2002 John Wiley & Sons, Ltd.
The effect of 12‐O‐tetradecanoylphorbol‐13‐acetate on Sertoli cell morphology and cytoskeletal organization: an in vitro study by means of cryo‐SEM and fluorescent techniques
Authors: Panagopoulou Evridiki , Kouloukoussa Mirsini , Voloudaki‐Baltatzi Irene , Kittas Christos , Marinos Evangelos 
Published: October 2002

AbstractBy means of cryo‐scanning electron microscopy (cryo‐SEM) and fluorescent techniques, evidence is provided on how 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) affects Sertoli cell morphology and F‐actin and vinculin organization in vitro. In order to visualize the morphological changes, the cells were observed with cryo‐SEM. F‐actin was localized using rhodamine (TRI)–phalloidin and vinculin using a primary monoclonal antibody and a second TRI‐conjugated antibody. The results indicate that after the addition of 10−7 M TPA, Sertoli cells begin to round up and their cytoplasm is retracted towards a central region. Actin bundle organization is disrupted and vinculin assumes a punctuate distribution throughout the cell. Thus, the reorganization of actin and vinculin and subsequent changes in cell morphology seem to be brought about by TPA affecting not only actin but also the protein vinculin which interacts with actin. A discussion is made concerning the effect of TPA on cytoskeletal reorganization, which is closely related to cell transformation.
Chemotherapy‐induced cardiotoxicity: current practice and prospects of prophylaxis
Authors: Gharib M.I. , Burnett A.K. 
Published: October 2002

AbstractCardiotoxicity is a potential side effect of few chemotherapeutic agents. The anthracycline class of cytotoxic antibiotics are the most famous, but other chemotherapeutic agents can also cause serious cardiotoxicity and are not so well recognised. Examples include cyclophosphamide, ifosfamide, mitomycin and fluorouracil. Prediction and hence prophylaxis has always been a difficult task. Ideal monitoring techniques, upon which efficient prophylaxis depends, are yet to be determined. Current prophylaxis relies upon early detection of systolic and/or diastolic dysfunction. While somewhat useful, in some cases by the time defects are detected progression of chemotherapy‐induced cardiomyopathy is beyond prevention. Prophylaxis would be much more efficient if a biochemical marker of myocardiocyte damage could be reliably used to stop further chemotherapy at the correct time before irreversible progressive ‘macroscopic’ damage becomes evident upon imaging. Work is currently progressing to identify the role of markers such as troponins and natriuretic peptides in this regard.
CNMs/CMs as Primary Care Providers: Scope of Practice Issues
Authors: Sullivan Nancy H. 
Published: October 2002

ABSTRACTSince the proliferation of managed care organizations and the expansion of the central role of the primary care provider in the early 1990s, certified nurse‐midwives and certified midwives have debated the merits and drawbacks of their inclusion in this category of provider. The present article explores the history of primary care and reviews the most commonly accepted definition of primary care. The boundaries of scope of practice in primary care and the legal and economic ramifications of certified nurse‐midwives/certified midwives practice in this area are discussed.
Journal Reviews
Authors: Zeidenstein Laura 
Published: October 2002

Distribution of genital tract trauma in childbirth and related postnatal pain. Albers L, Garcia J, Renfrew M, McCandlish R, Elbourne D. Birth 1999;26:11–5.Reviewed by: Suzanne Seger, CNM, MSN, Mount Sinai Medical Center Midwifery Service, New York, New York.Association between method of delivery and maternal rehospitalization. Lydon‐Rochelle M, Holt VL, Martin DP, Easterling TR. J Am Med Assoc 2000;283(18):2411–6.Reviewed by: Kimberly A. Whitfill, MSN, CNM, Assistant Clinical Professor, Columbia University School of Nursing/Nurse‐Midwifery Program, New York, New York.Is it necessary to suture all lacerations after a vaginal birth? Lundquist M, Olsson A, Nissen E, Norman M. Birth 2000;27:79–85.Reviewed by: Kathy Rosenberg, CNM, MS, Katonah, New York.Effect of a screening‐based prevention policy on prevalence of early‐onset group B streptococcal sepsis. Brozanski BS, Jones JG, Krohn MA, Sweet RL. Obstet Gynecol 2000;95:496–501.Reviewed by: Jessica Lynn, GNM, MSN, Columbia University School of Nursing, New York, New York.