bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal Cell Carcinoma in Children: A Clinicopathologic Study
Authors: Indolfi Paolo , Terenziani Monica , Casale Fiorina , Carli Modesto , Bisogno Gianni , Schiavetti Amalia , Mancini Antonia , Rondelli Roberto , Pession Andrea , Jenkner Alessandro , Pierani Paolo , Tamaro Paolo , De Bernardi Bruno , Ferrari Andrea , Santoro Nicola , Giuliano Maria , Cecchetto Giovanni , Piva Luigi , Surico Gianmarco , Di Tullio M. Teresa
Published: January 2003

Purpose: To identify the prognostic factors, treatment, and outcome of children affected by renal cell carcinoma (RCC).

Patients and Methods: The series included 41 patients (18 males and 23 females) with a median age of 124 months observed at the 11 Italian Association for Pediatric Hematology and Oncology centers from January 1973 to January 2001. Clinical data, surgical notes, pathologic findings, and summaries of therapy were taken from the charts.

Results: Seven (17%) of the 41 patients had a papillary histology, and 34 (82.4%) had nonpapillary histology. Eighteen patients (43.9%) had stage I, one patient (2.4%) had stage II, two patients (4.8%) had stage IIIA, 10 patients (24.3%) had stage IIIB, and nine patients (21.9%) had stage IV disease. One patient had a bilateral involvement at diagnosis. Seven patients experienced disease recurrence. Lung and liver were the most common distant lesions and usually were fatal. In this study, the major factor influencing the prognosis was the stage. Event-free survival at 20 years was 53.5% for all patients. Overall survival at 20 years was 54.9% for all patients.

Conclusion: RCC is a rare disease in children and adolescents. This neoplasm has a different clinical presentation in children compared with adults but the same outcome. In our experience, patients with localized disease could be cured by nephrectomy alone. Prospective studies in a larger number of patients are needed to confirm radiation therapy and biologic response modifiers as effective adjunct therapy in RCC stage III. The alternative therapy seems warranted in patients with advanced disease.
Value of P-Glycoprotein and Clinicopathologic Factors as the Basis for New Treatment Strategies in High-Grade Osteosarcoma of the Extremities
Authors: Serra Massimo , Scotlandi Katia , Reverter-Branchat Gemma , Ferrari Stefano , Manara Maria C. , Benini Stefania , Incaprera Marina , Bertoni Franco , Mercuri Mario , Briccoli Antonio , Bacci Gaetano , Picci Piero
Published: January 2003

Purpose: To evaluate the prognostic value of P-glycoprotein and clinicopathologic parameters in a large series of high-grade osteosarcoma (OS) patients treated at the Rizzoli Institute.

Patients and Methods: With the use of immunohistochemistry, P-glycoprotein was assessed in 149 patients with primary, nonmetastatic, high-grade OS who were homogeneously treated with chemotherapy protocols based on doxorubicin, high-dose methotrexate, and cisplatin and the addition of ifosfamide in the postoperative phase.

Results: P-glycoprotein positivity was found in 47 of 149 cases (32%) and was significantly associated with a higher incidence of relapse and a worse outcome, as was age younger than 12 years and tumor volume greater then 150 mL at diagnosis. Multivariate analysis further confirmed the prognostic value of these parameters, which all were independent adverse prognostic factors. Event-free survival and proportional hazards regression analyses confirmed that overexpression of P-glycoprotein at clinical onset is the most important adverse prognostic factor for high-grade OS patients treated with these chemotherapy protocols.

Conclusion: Increased P-glycoprotein levels, together with tumor volume and age, should be taken into consideration to identify, at time of diagnosis, subgroups of OS patients with a higher risk of recurrence. This subgroup identification will constitute the basis for drawing individualized treatment protocols on the basis of risk evaluation, with the aim of using more aggressive chemotherapy, or combination chemotherapy with other adjuvants, only in those patients for which more aggressive regimens are strictly necessary and warranted.
Whole Body 18FDG-PET and the Response of Esophageal Cancer to Induction Therapy: Results of a Prospective Trial
Authors: Downey Robert J. , Akhurst Tim , Ilson David , Ginsberg Robert , Bains Manjit S. , Gonen Mithat , Koong Heng , Gollub Marc , Minsky Bruce D. , Zakowski Maureen , Turnbull Alan , Larson Steven M. , Rusch Valerie
Published: January 2003

Purpose: Whole-body 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) imaging before and after induction therapy was prospectively evaluated in patients with esophageal cancer to determine whether changes in PET images could measure response to therapy.

Patients and Methods: Between April 1997 and April 1999, 39 patients (34 men and five women; median age, 59 years; range, 36 to 76 years) with esophageal cancer were prospectively enrolled in a single-institution clinical trial of staging, including PET, induction therapy, restaging including PET, and esophagectomy. All patients undergoing esophagectomy after induction therapy (n = 17) were followed either to recurrence, to death, or through a disease-free interval of at least 24 months.

Results: PET after standard staging studies and before therapy imaged undetected sites of metastatic disease in six patients (15%). Restaging (including PET) after induction therapy did not identify any patients with disease progression or any patients with loco-regionally unresectable disease at exploration. The median decrease in the standardized uptake value (SUV) during induction therapy was 59%. After R0 esophagectomy, the 2-year disease-free and overall survival was 38% and 63%, respectively, among patients who had a less than 60% decrease in SUV, and 67% and 89%, respectively, among patients who had a greater than 60% decrease in SUV (P = .055 and P = .088, respectively).

Conclusion: Compared with conventional imaging, PET detects additional sites of metastatic disease at initial evaluation. After induction therapy, PET did not add to the estimation of loco-regional resectability and did not detect new distant metastases. However, changes in [18F]FDG PET may predict disease-free and overall survival after induction therapy and resection in patients with esophageal cancer. Further evaluation in larger trials is warranted.
Role of Surgeon Volume in Radical Prostatectomy Outcomes
Authors: Hu Jim C. , Gold Karen F. , Pashos Chris L. , Mehta Shilpa S. , Litwin Mark S.
Published: January 2003

Purpose: To examine the effect of hospital and surgeon volume on postoperative outcomes and to determine whether hospital or surgeon volume is the stronger predictor.

Patients and Methods: Using 1997 to 1998 claims data from a national 5% random sample of Medicare beneficiaries, we identified 2,292 men who underwent radical prostatectomy at 1,210 hospitals by 1,788 surgeons. Hospitals were classified as high (≥ 60 per year) or low (< 60 per year) volume according to radical prostatectomy experience over the 2-year period. Surgeons were classified as high (≥ 40 per year) or low (< 40 per year) volume. Multivariate logistic regression was performed to control for patient demographics and comorbidities when assessing the association of hospital and surgeon volume with in-hospital complications, length of stay, and anastomotic stricture rates. In-hospital complications included cardiac, respiratory, vascular, wound, genitourinary, and miscellaneous surgical and medical conditions.

Results: High-volume surgeons had half the complication risk (odds ratio [OR] = 0.53; 95% confidence interval [CI], 0.32 to 0.89) and shorter lengths of stay (4.1 v 5.2 days, P = .03) compared with low-volume surgeons. High-volume hospital patients tended to have fewer anastomotic strictures (OR = 0.72; 95% CI, 0.49 to 1.04). Patient age (≥ 75 years) was associated with more complications (OR = 1.9; 95% CI, 1.39 to 2.70), more anastomotic strictures (OR = 2.2; 95% CI, 1.54 to 3.15), and longer hospital stays (parameter estimate = 2.26; 95% CI, 1.75 to 2.77).

Conclusion: Surgeon volume is inversely related to in-hospital complications and length of stay in men undergoing radical prostatectomy. Hospital volume is not significantly associated with outcomes after adjusting for physician volume. Further study is necessary to elucidate the mechanism of the volume-outcome effect.
Estrogen Receptor Classification for Hepatocellular Carcinoma: Comparison With Clinical Staging Systems
Authors: Villa Erica , Colantoni Alessandra , Cammà Calogero , Grottola Antonella , Buttafoco Paola , Gelmini Roberta , Ferretti Ilva , Manenti Federico
Published: January 2003

Purpose: Several scoring systems to evaluate patients with hepatocellular carcinoma (HCC) exist. A good scoring system should provide information on prognosis and guide therapeutic decisions. The presence of variant liver estrogen receptor (ER) transcripts in the tumor has been shown to be the strongest negative predictor of survival in HCC. The aim of this study was to compare the predictive value of the commonly applied clinical scoring systems for survival of patients with HCC with that of the evaluation of ER in patients with HCC (molecular scoring system).

Materials and Methods: HCC was staged according to the Okuda classification, Barcelona Clinic Liver Cancer classification, Italian classification system (CLIP), French classification, and ER status in 96 patients. Analysis of survival was performed according to the Kaplan-Maier test and was made for each classification system and ER. A comparison between classifications was made by univariate and multivariate analysis.

Results: Among the clinical classification systems, only the CLIP was able to identify patient populations with good, intermediate, and poor prognosis. On multivariate analysis, ER classification was shown to be the best predictive classification for survival of patients with HCC (P <.0001). This difference was the result of a better allocation of patients with ominous prognosis (variant ER) having nevertheless good clinical score.

Conclusion: The evaluation of the presence of wild-type or variant ER transcripts in the tumor is the best predictor of survival in patients with HCC. Its accuracy in discriminating patients with good or unfavorable prognosis is significantly greater than that of the commonly used scoring systems for the staging of HCC.
Diminished Survival in Patients With Inner Versus Outer Quadrant Breast Cancers
Authors: Gaffney David K. , Tsodikov Alexander , Wiggins Charles L.
Published: January 2003

Purpose: To evaluate the role of breast tumor location on survival in patients with breast cancer.

Patients and Methods: We evaluated tumor location within the breast on breast cancer–specific survival (BCSS) and overall survival (OS) in patients with invasive breast cancer using the Surveillance, Epidemiology, and End-Results (SEER) registries in the United States. Effects on survival were evaluated according to age, stage, tumor site, tumor size, grade, axillary lymph node status, extent of surgery, and radiotherapy (RT). A multivariate model was used with complete data on 45,880 patients. The median follow-up was 59 months.

Results: Patients with outer tumor location demonstrated superior BCSS on Kaplan-Meier analysis for both local stage (node-negative, P < .001) and regional stage disease (node-positive, P = .0002). For BCSS, the hazard ratio (HR) for inner quadrant location compared with outer quadrant was 1.31 (95% confidence interval [CI], 1.19 to 1.37; P < .001); and for OS, the HR was 1.12 (95% CI, 1.05 to 1.17; P < .001). When ER and PR status were included in the model, the HR for inner quadrant location compared with outer quadrant was 1.27 for BCSS (95% CI, 1.16 to 1.40; P < .001) and 1.11 for OS (95% CI, 1.03 to 1.19; P = .004). Patients treated by lumpectomy that received RT had a superior OS compared with patients that did not receive RT in both local (HR, 0.52; 95% CI, 0.48 to 0.61; P < .001) and regional (HR, 0.63; 95% CI, 0.56 to 0.72; P < .001) stage disease. Mastectomy patients with local stage disease that received RT had a diminished OS (HR, 1.24; 95% CI, 1.02 to 1.50; P = .033).

Conclusion: On multivariate analysis, incorporating data on age, stage, tumor site, tumor size, grade, ER and PR status, axillary lymph node status, extent of surgery, and RT, this SEER registry–based study demonstrates that medial tumor location adversely impacts BCSS and OS.
The role of small‐scale orographic features in the spatial distribution of precipitation
Authors: Cosma S. , Richard E. , Miniscloux F.
Published: January 2003

Radar images from the Cévennes experiment, which took place during the autumns of 1986–88 on the southeastern flank of the Massif Central in France, reveal a characteristic and repetitive structure of the precipitation distribution. In southerly Mediterranean flows, which are frequent there in autumn, precipitation is often organized into narrow bands or plumes, oriented south–north.

The period 14 and 15 November 1986 has been selected as an example on which to perform numerical simulations and analyse the mechanism yielding this specific precipitation organization. The numerical model correctly reproduces the bands, especially at high horizontal resolution (1 km). These rainfall bands are focused on the small‐scale topography, oriented east–west, composed of a succession of ridges and penetrating valleys. The bands are generated upstream of these ridges and enhanced on the lee side by convergence created by deflection around the obstacle and penetration of the flow into the valleys.

Idealized simulations and sensitivity experiments have been carried out to verify these hypotheses. These simulations suggest that small‐scale orography plays a decisive role in forcing the precipitation into bands, while upstream moisture conditions mainly affect the precipitation intensity and its south–north extent. Copyright © 2002 Royal Meteorological Society.
Relationship between cloud‐to‐ground lightning flashes over the Iberian Peninsula and sea surface temperature
Authors: Pablo Fernando De , Soriano Luis Rivas
Published: January 2003

The correlation between cloud‐to‐ground (CG) lightning anomalies over the Iberian peninsula and sea surface temperature (SST) anomalies in its bordering seas has been calculated. The results disclosed a significant link between them. The warmer SSTs in the Atlantic north‐west of the Iberian Peninsula and in the Cantabrian Sea are related to increased CG lightning activity over the Iberian Peninsula. The warmer SSTs in the Atlantic south of the Iberian Peninsula are related to increased CG lightning over the northern half of the Iberian Peninsula and to decreased CG lightning over the southern half. The Mediterranean Sea does not show significant links with CG lightning. The way these links work seems to involve changes in the advection of moisture from the Atlantic Ocean and the Cantabrian Sea as well as changes in static instability. It was also observed that there is no significant link between CG lightning anomalies and land surface temperature anomalies over the Iberian Peninsula. Copyright © 2002 Royal Meteorological Society.
Influence of added observations on analysis and forecast errors: Results from idealized systems
Authors: Morss R. E. , Emanuel K. A.
Published: January 2003

Recent tests of adding observations to improve individual forecasts have shown a mix of positive, negative, and neutral results. In this study, the influence of added observations on analysis and forecast errors is explored in idealized systems. The primary system studied is a three‐dimensional simulated observing and forecasting system that includes a quasi‐geostrophic forecast model and a three‐dimensional variational data‐assimilation system. In this simulated system, adding observations generally improves analyses and often improves 12‐hour forecasts. Even with perfect observational data and a perfect forecast model, however, there is a non‐negligible risk that adding observations will degrade analyses, and a significant risk that assimilated added observations will degrade forecasts on a time‐scale of one or several days. To illustrate several general principles that help interpret the results, several experiments are performed with low‐dimensional data‐assimilation systems; the results demonstrate that the risk of analysis degradation is inherent in statistical data assimilation. Experiments are also performed with a low‐dimensional forecast model, demonstrating that the risk of forecast degradation is inherent in prediction systems with sensitivity to small errors in initial conditions. Although degradations cannot be avoided, several circumstances are identified in which adding observations is less likely to degrade analyses and forecasts and on average improves analyses and forecasts by a larger amount. Copyright © 2002 Royal Meteorological Society.
Lagrangian description of airflows using Eulerian passive tracers
Authors: Gheusi François , Stein Joël
Published: January 2003

A method of tracking coherent Lagrangian airmasses is presented. It is not based on the computation of individual trajectories, but rather on three Eulerian passive tracers initialized with the coordinates of each grid cell. This ‘initial coordinates’ method allows the later unambiguous identification of each Lagrangian air parcel by referring to its initial position. Further, the physical history of each parcel can be retrieved. The advantages of this method in the framework of mesoscale numerical modelling are discussed with respect to trajectory‐based methods. Preliminary examples are given by studying idealized airflows: (i) a two‐dimensional stratified flow past an isolated obstacle generating gravity‐wave breaking; (ii) a deep convective squall line. Then the method is applied to a heavy‐rain situation over the Alps during the Mesoscale Alpine Programme (MAP) field phase. A coherent mesoscale pool of dry air is identified over the Mediterranean and tracked with the aid of the initial‐coordinates method. Its influence on the rain distribution over the Ligurian Alps and Apennines is demonstrated. Copyright © 2002 Royal Meteorological Society.
A Study on the Seismic Response of Lattice Shells
Authors: Cao Zi , Zhang Yigang
Published: January 2003

A thorough investigation on the seismic response of lattice shells is presented in this paper. Based on the theoretical analysis and hundreds of calculating examples, conclusions on the seismic performances of lattice shells are obtained. As a result, practical methods on calculating internal forces for lattice shells due to earthquake are introduced in the Technical Specification for Lattice Shells in China.
Evaluation Method for Predicting Dynamic Collapse of Double Layer Latticed Space Truss Structures due to Earthquake Motion
Authors: Ishikawa Koichiro , Okubo Shoji , Hiyama Yujiro , Kato Shiro
Published: January 2003

For a structure due to severe earthquake motion, a method for predicting the ultimate state may be needed to the seismic design. The purpose of this paper is to present the evaluation method using the simplified model and linear analysis in order to predict the dynamic buckling collapse of an aluminium alloy double layer latticed roof supported by two double layer latticed walls. In the study, the elastic-plastic analysis considering both geometric and member buckling nonlinearities is carried out. And also the critical displacement at the top of the wall corresponding to the ultimate state of the wall is shown to be useful for determining the dynamic collapse. Finally, the method for estimating the maximum amplitude of the input earthquake motion, due to which the structure brings about the dynamic collapse, is proposed by using the investigated critical displacement. And the accuracy of the proposed method and the conditions for the applicability are discussed in comparison of the numerical results and the estimated values.
The Influence of Geometrical Tolerances on the Behaviour of Space Structures
Authors: Băluţ Nicolae , Gioncu Victor
Published: January 2003

The behaviour of reticulated space structures is characterised by some peculiarities which make the influence of geometrical imperfections (and consequently that of geometrical tolerances) more complex and more important than in the case of other categories of structures. In addition to their adverse effect on the bearing capacity of compression members, initial bows (in conjunction with mechanical imperfections, mainly residual stresses) give rise to an apparent reduction of their axial stiffness. As for deviations of the member lengths form the nominal values, their effect depends on the type of joint connecting system (‘adjustable’ or ‘non-adjustable’) and on the category of space structure under consideration (single or double-layer).
Key Points in Design of the Sheet Space Structure System
Authors: Zhao H. L. , Ma J. , Zhao C. Q. , She Y. H. , Guo X. M. , Yin L. F.
Published: January 2003

In this paper the key problems related to the structural theory of the sheet space system are discussed. The principles for selection of the structure form and the mechanical analysis are described briefly. For the purpose of simplifying the design of this system the main functions of the professional software is narrated at the end and some related diagrams showing the influence of imperfection of structure on stability are also attached to the paper.
Cross‐reactivity with myelin basic protein and human herpesvirus‐6 in multiple sclerosis
Authors: Tejada‐Simon Maria V. , Zang Ying C. Q. , Hong Jian , Rivera Victor M. , Zhang Jingwu Z.
Published: January 2003

Viral infections are though to play an important role in the pathogenesis of multiple sclerosis (MS) potentially through molecular mimicry. An identical sequence was found in both myelin basic protein (MBP, residues 96–102), a candidate autoantigen for MS, and human herpesvirus‐6 (HHV‐6 U24, residues 4–10) that is a suspected viral agent associated with MS. In this study, we showed that greater than 50% of T cells recognizing MBP93‐105 cross‐reacted with and could be activated by a synthetic peptide corresponding to residues 1 to 13 of HHV‐6 U24 in MS patients. The estimated precursor frequency of these cross‐reactive T cells recognizing both peptides, MBP93‐105 and HHV‐6 (U24)1‐13, was significantly elevated in MS patients compared with that in healthy controls. These cross‐reactive CD4+ T cells represented the same Th1 phenotype as that of monospecific T cells recognizing MBP93‐105. There were increased antibody titers for both peptide HHV‐6 (U24)1‐13 and peptide MBP93‐105 in the same patients with MS compared with those in healthy controls, suggesting B‐cell sensitization to the antigens in MS patients. The study provides important evidence in the understanding of the potential role of HHV‐6 infection/reactivation in the activation of autoimmune reactivity to MBP and its implication in the pathogenesis of MS. Ann Neurol 2003
Suppression of complex I gene expression induces optic neuropathy
Authors: Qi Xiaoping , Lewin Alfred S. , Hauswirth William W. , Guy John
Published: January 2003

Optic nerve degeneration is a feature common to diseases with mutations in genes that encode complex I of the respiratory chain. Vulnerability of this central nervous system tract is a mystery, because of the paucity of animal models used to investigate effects of the mutated DNA in tissues rather than isolated in cultured cells. Using a ribozyme designed to degrade the mRNA encoding a critical nuclear‐encoded subunit gene of complex I (NDUFA1), we tested whether oxidative phosphorylation deficiency can recapitulate the optic neuropathy of mitochondrial disease. Injection of adenoassociated virus expressing this ribozyme led to axonal destruction and demyelination, the hallmarks of Leber hereditary optic neuropathy. Ann Neurol 2003
Plasticity of the nigropallidal pathway in Parkinson's disease
Authors: Whone Alan L. , Moore Robert Y. , Piccini Paola P. , Brooks David J.
Published: January 2003

The degeneration of nigrostriatal dopamine neurons in early Parkinson's disease (PD) is compensated in part by increased transmitter turnover in surviving neurons of the pathway. In this 18F‐dopa positron emission tomography study, we demonstrate compensatory changes in PD in another midbrain dopamine projection to the basal ganglia, the nigropallidal projection to the internal segment of the globus pallidus (GPi). Increased 18F‐dopa uptake in the GPi is seen in early PD which then is lost in advanced PD. Our early PD cases show an absence of significant clinical progression in the face of a continuing loss of nigrostriatal projections. This indicates a compensatory neuronal plasticity that we now show to involve the nigropallidal dopamine pathway to the GPi but not to the external segment of the globus pallidus (GPe). Enhanced function of the dopamine projection to the GPi serves, we propose, to maintain a more normal pattern of pallidal output to ventral thalamus and motor cortex in early PD, whereas loss of this adaptive pathway in advanced disease may be a pivotal step in the progression of the disease.
Homocysteine, white matter hyperintensities, and cognition in healthy elderly people
Authors: Dufouil Carole , Alpérovitch Annick , Ducros Véronique , Tzourio Christophe
Published: January 2003

Hyperhomocysteinemia is associated with an increased risk of vascular disease, and recent results suggest that it also could increase the risk of dementia. We examined the relationship between homocysteine and cognitive decline in 1,241 subjects aged 61 to 73 years, followed up over 4 years. Plasma homocysteine levels were determined in all participants as well as cardiovascular risk factors, apolipoprotein E genotype, plasma levels of folate, and vitamin B12. Cognitive performances were assessed repeatedly by using Mini‐Mental State Examination, Trail Making Test, Digit Symbol Substitution Test, and Finger Tapping Test. At 2‐year follow‐up, 841 subjects underwent cerebral magnetic resonance imaging, and white matter hyperintensities were rated visually. Analyses were adjusted for all cardiovascular risk factors. Cross‐sectional analyses showed that higher concentrations of homocysteine were significantly related to poorer performances at all neuropsychological tests. Longitudinal analyses confirmed this finding. The odds of cognitive decline was 2.8‐fold (p < 0.05) higher in subjects with homocysteine levels above 15μmol/L compared with those with homocysteine levels below 10μmol/L. In participants who underwent magnetic resonance imaging, the relationship between homocysteine and cognition was unchanged after taking into account white matter hyperintensities suggesting that white matter hyperintensities do not mediate the association between homocysteine and cognition. Ann Neurol 2003;53:000–000
Lack of creatine in muscle and brain in an adult with GAMT deficiency
Authors: Schulze Andreas , Bachert Peter , Schlemmer Heinz , Harting Inga , Polster Tilman , Salomons Gajja S. , Verhoeven Nanda M. , Jakobs Cornelis , Fowler Brian , Hoffmann Georg F. , Mayatepek Ertan
Published: January 2003

Guanidinoacetate methyltransferase deficiency, which so far has been exclusively detected in children, was diagnosed in a 26‐year‐old man. The full‐blown spectrum of clinical symptoms already had been present since infancy without progression of symptoms during adolescence. Cranial magnetic resonance imaging showed normal findings. Ophthalmological examination showed no retinal changes. Besides creatine deficiency in the brain, a distinct lack of phosphocreatine in skeletal muscle was proved by 31P magnetic resonance spectroscopy. Creatine substitution combined with a guanidinoacetate‐lowering diet introduced first at the age of 26 years was shown to be effective by an impressive improvement of epileptic seizures, mental capabilities, and general behavior and by normalization of the 31P spectrum in the skeletal muscle.
Oculobulbar involvement is typical with Lambert–Eaton Myasthenic Syndrome
Authors: Burns Ted M. , Russell James A. , LaChance Daniel H. , Jones H. Royden
Published: January 2003

Oculobulbar symptoms and/or signs were present in 18 of 23 (78%) of Lambert–Eaton myasthenic syndrome (LEMS) patients evaluated at the Lahey Clinic (Table). Sixty‐five percent (15 of 23) of our patients had ptosis and/or diplopia, each present in 11 individuals. Bulbar signs and symptoms, including dysarthria in 10 and dysphagia in 8 patients, also were observed among our LEMS population. More than one prereferral oculobulbar feature occurred in 13 of our LEMS patients. Prereferral diagnostic considerations included myasthenia gravis, myopathies, and psychiatric disorders. These findings suggest that these atypical characteristics served to dissuade some colleagues from a diagnosis of LEMS. Thus, the presence of oculobulbar symptoms and signs cannot be used to exclude LEMS from the differential diagnosis.
High exogenous homocysteine modifies eye development in early chick embryos
Authors: Maestro De Las Casas Carmen , Epeldegui Marta , Tudela Consuelo , Varela‐Moreiras Gregorio , Pérez‐Miguelsanz Julia
Published: January 2003

BACKGROUND

Homocysteine is a nonessential aminoacid whose increase is related to the appearance of neural tube defects in humans. In chick embryos, high levels of homocysteine produce neural tube defects and alteration of neural crest cell migration.

METHODS

In our study, 8 μl of L‐homocysteine thiolactone (20 μmol) was added to chick embryos of Stages 3–8/10 (Hamburger and Hamilton, 1951), (12–38 hr of incubation). Three days later, 50 embryos, externally normal or carrying isolated spinal neural tube defects, were sectioned and stained by hematoxilin‐eosin or anti‐fibrillin‐1 antibody.

RESULTS

The eye showed alterations of the optic cup as microphthalmia, or lens dislocation. In both cases, the incidence of alterations diminished with the age of the homocysteine‐increased embryos. Optic cup modifications are probably associated with central nervous system alterations, because most of the affected embryos exhibited isolated spinal neural tube defects and had altered neural crest cells. We have shown for the first time that high exogenous homocysteine during early development could produce a caudally‐displaced lens axis before the zonule is formed. Fibrillin‐1 is the main component of elastic microfibrils, and in the adult human it is seen as a protein particularly susceptible to homocysteine attack.

CONCLUSIONS

Antibody staining against fibrillin‐1 showed no evident morphological differences in distribution between experimental and control embryos in the lens, suggesting that fibrillin‐1 was not the cause, and malformations may be attributed to other mechanisms. Birth Defects Research (Part A) 67:35–40, 2003. © 2003 Wiley‐Liss, Inc.
Defects in cervical vertebrae in boric acid‐exposed rat embryos are associated with anterior shifts of hox gene expression domains
Authors: Wéry Nathalie , Narotsky Michael G. , Pacico Nathalie , Kavlock Robert J. , Picard Jacques J. , Gofflot Françoise
Published: January 2003

BACKGROUND

Previously, we showed that prenatal exposure to boric acid (BA), an industrial agent with large production, causes alterations of the axial skeleton in rat embryos, reminiscent of homeotic transformations. Indeed, Sprague‐Dawley rats exposed in utero to BA on gestation day 9 (GD 9) had only six, rather than the normal seven, cervical vertebrae. This finding, observed in 91% of GD 21 fetuses, suggests posterior transformations of vertebrae. The present study attempts to determine if these skeletal alterations could be explained by modifications of the hox code, involved in the establishment of positional information along the craniocaudal axis of the embryo.

METHODS

Pregnant rats were treated by gavage with BA (500 mg/kg, twice) on GD 9. Embryos were collected on GD 11 or GD 13.5 and processed for in situ hybridization. Several hox genes were selected according to the position of their cranial limit of expression in the cervical and thoracic region.

RESULTS

At GD 13.5, we detected a cranial shift of the anterior limit of expression of hoxc6 and hoxa6. We observed no difference between control and treated embryos in the location of the cranial limit of expression of the other genes: hoxd4, hoxa4, hoxc5, and hoxa5.

CONCLUSIONS

Our results demonstrate that following in utero exposure to BA on GD 9, a disturbance of the expression of hox genes involved in the specification of most anterior vertebrae is observed at GD 13.5. Based on their expression domain and on their implication in the definition of the cervicothoracic vertebral boundary, it is likely that the anteriorization of hoxc6 and hoxa6 reported here is correlated to the morphological phenotype observed in BA‐exposed fetuses at GD 21. Birth Defects Research (Part A) 67:59–67, 2003. © 2003 Wiley‐Liss, Inc.
Human c‐fos promoter mediates high‐level, inducible expression in various mammalian cell lines
Authors: Bi Jing‐Xiu , Buhr Petra , Zeng An‐Ping , Wirth Manfred
Published: January 2003

The promoter activity of the human c‐fos and human cytomegalovirus (CMV) immediate early promoter was compared in transient and stable transfection experiments with six cell lines of mouse, human, and hamster origin which are all of commercial importance. The c‐fos promoter was 1.8–5.6‐fold stronger than the CMV promoter in BHK‐A, BHK‐B, CHO‐DHFR−, and mouse NIH‐3T3 in stable transfectants and less effective in mouse myeloma or human 293 cells, suggesting a new transcriptional control element for high‐level expression and protein production in mammalian cells. The induction profiles determined in the presence and absence of serum are dependent on the cell line used. Induction levels of up to 8‐fold could be achieved in preselected cell pools. © 2003 Wiley Periodicals. Biotechnol Bioeng 81: 848–854, 2003.
Capture of a recombinant protein from unclarified canola extract using streamline expanded bed anion exchange
Authors: Bai Yun , Glatz Charles E.
Published: January 2003

The feasibility of applying expanded bed adsorption technology to recombinant protein recovery from extracts of transgenic canola (rapeseed) was assessed. The extraction step results in a suspension of high solids content that is difficult to clarify. The coarse portion of the solids can be removed easily, and our aim was to operate the expanded bed in the presence of the recalcitrant particulates. Recombinant β‐glucuronidase (rGUS) produced in transgenic canola seed was the model system. Diethylaminoethyl (DEAE) and Streamline DEAE resin exhibited similar binding and elution properties for both rGUS and native canola proteins. More than 95% of native canola proteins did not bind to DEAE resins at pH 7.5, whereas the bound proteins were fractionated by two‐step salt elution into two groups with the first peak, containing 70% of total bound proteins, at 20 mS/cm, followed by elution of rGUS at 50 mS/cm. The adsorption isotherm was only slightly influenced by the presence of up to 14 mg solids/mL extract; Cm and Kd changed by −1% and +39%, respectively. Bed expansion was semiquantitatively predictable from physical properties of the fluid together with Stokes's law and the Richardson–Zaki correlation for both clarified and partially clarified extracts. The presence of 1.4% solids did not change rGUS breakthrough behavior of the expanded bed; however, a small difference between expanded bed and packed bed was observed early in the sample loading stage, during which bed expansion adjusts. Canola solids moved through the column in approximately plug flow with no detriment to bed stability. Seventy‐two percent recovery of 34‐fold purified rGUS was obtained after initial loading of 1.4% (w/w) solids extract to 25% breakthrough. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 81: 855–864, 2003.
Integrated optical sensing of dissolved oxygen in microtiter plates: A novel tool for microbial cultivation
Authors: John Gernot T. , Klimant Ingo , Wittmann Christoph , Heinzle Elmar
Published: January 2003

Microtiter plates with integrated optical sensing of dissolved oxygen were developed by immobilization of two fluorophores at the bottom of 96‐well polystyrene microtiter plates. The oxygen‐sensitive fluorophore responded to dissolved oxygen concentration, whereas the oxygen‐insensitive one served as an internal reference. The sensor measured dissolved oxygen accurately in optically well‐defined media. Oxygen transfer coefficients, kLa, were determined by a dynamic method in a commercial microtiter plate reader with an integrated shaker. For this purpose, the dissolved oxygen was initially depleted by the addition of sodium dithionite and, by oxygen transfer from air, it increased again after complete oxidation of dithionite. kLa values in one commercial reader were about 10 to 40 h−1. kLa values were inversely proportional to the filling volume and increased with increasing shaking intensity. Dissolved oxygen was monitored during cultivation of Corynebacterium glutamicum in another reader that allowed much higher shaking intensity. Growth rates determined from optical density measurement were identical to those observed in shaking flasks and in a stirred fermentor. Oxygen uptake rates measured in the stirred fermentor and dissolved oxygen concentrations measured during cultivation in the microtiter plate were used to estimate kLa values in a 96‐well microtiter plate. The resulting values were about 130 h−1, which is in the lower range of typical stirred fermentors. The resulting maximum oxygen transfer rate was 26 mM h−1. Simulations showed that the errors caused by the intermittent measurement method were insignificant under the prevailing conditions. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 81: 829–836, 2003.
On the organic solvent and thermostability of the biocatalytic redox system of Rhodococcus ruber DSM 44541
Authors: Stampfer Wolfgang , Kosjek Birgit , Kroutil Wolfgang , Faber Kurt
Published: January 2003

The sec‐alcohol dehydrogenase activity of whole cells of Rhodococcus ruber DSM 44541 has been employed as an efficient biocatalytic redox system due to the use of acetone and 2‐propanol at elevated concentrations for cofactor regeneration in the oxidation and reduction mode, respectively, and external addition of NADH/NAD+ can be omitted. The operational half‐life time of the redox system is 29 hours in 20% v/v acetone and 37 hours in 30% v/v 2‐propanol. The Redox system allows the enantioselective oxidation of sec‐alcohols and the asymmetric reduction of ketones to furnish (S)‐configurated alcohols in high optical purity. The stability of the cells towards further organic solvents was investigated. In addition, the system displays thermostability of up to 60°C and pH stability of up to pH 11. The system represents a simple to handle tool for environmentally benign redox reactions. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 81: 865–869, 2003.
Objective countertransference: do patients' interpersonal impacts generalize across therapists?
Authors: Hafkenscheid Anton
Published: January 2003

Objective countertransference refers to the constricted feelings, attitudes and reactions of a therapist, that are induced primarily by the patient's maladaptive behaviour and that are generalizable to other therapists (and to other significant others in the patient's life). In interpersonal theory and therapy, the equivalent of objective countertransference is the impact message concept. Impact messages refer to the cognitions, emotions and action tendencies evoked in the therapist by a particular patient's interpersonal pressures. This paper tests the interpersonal hypothesis that interpersonal impact generalizes across therapists (and by extension across interpersonal relationships). Generalizability of impact messages across therapists was determined for different combinations of therapist pairs, independently rating a total of 131 psychiatric outpatients with the IMI‐C (Impact Message Inventory, revised circumplex version). It was found that impact messages were most clearly generalizable across therapists for the Dominance (D) category, followed by the Hostile–Dominant (HD) and Hostile–Submissive (HS) categories. In contrast, the other five categories of impact messages turned out to be poorly generalizable across therapists. Impact messages within the Dominance (D) category were also strikingly stable over a period of time of 12 months or longer. Some possible causes of the limited generalizability of most impact message categories are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
A metamodel of theories of psychotherapy: a guide to their analysis, comparison, integration and use
Authors: Morris Steven J.
Published: January 2003

Every theory of psychotherapy is composed of a myth and an associated ritual. A myth is a conceptual scheme for explaining clinical problems. A ritual is based upon a myth and is a model of the clinical change process. This article goes far beyond the observation that theories of psychotherapy consist of a myth and a ritual to propose that they share a common underlying structure. The central purpose of this article is to delineate this structure. This structure constitutes a metamodel of theories of psychotherapy. The article shows how the metamodel is a fresh conceptual tool (a) for understanding, analysing, comparing and contrasting, and integrating the basic concepts and principles of theories of psychotherapy and (b) for building case formulations and treatment plans from a theory of psychotherapy. Copyright © 2003 John Wiley & Sons, Ltd.
Tales of regeneration in zebrafish
Authors: Poss Kenneth D. , Keating Mark T. , Nechiporuk Alex
Published: January 2003

Complex tissue regeneration involves exquisitely coordinated proliferation and patterning of adult cells after severe injury or amputation. Certain lower vertebrates such as urodele amphibians and teleost fish have a greater capacity for regeneration than mammals. However, little is known about molecular mechanisms of regeneration, and cellular mechanisms are incompletely defined. To address this deficiency, we and others have focused on the zebrafish model system. Several helpful tools and reagents are available for use with zebrafish, including the potential for genetic approaches to regeneration. Recent studies have shed light on the remarkable ability of zebrafish to regenerate fins. Developmental Dynamics 226:202–210, 2003. © 2003 Wiley‐Liss, Inc.
Hydra regeneration and epitheliopeptides
Authors: Fujisawa Toshitaka
Published: January 2003

Hydra has been well known for over 200 years for its remarkable regenerative capacity. In addition to small pieces excised from the body, reaggregates of dissociated single cells can also regenerate. Although the cellular events involved in the regeneration process have been well characterized, the underlying molecular mechanisms are yet to be uncovered. Recently, however, transcription factors and signaling molecules, both proteins and short peptides, have been identified and their role suggested in patterning and morphogenesis. In this article, a regeneration study at the tissue level is first described and then the importance of epithelial cells in regeneration is stressed. Finally, the recent study on morphogenetic peptides derived from epithelial cells is reviewed. Developmental Dynamics 226:182–189, 2003. © 2003 Wiley‐Liss, Inc.
Retinoic acid, a regeneration‐inducing molecule
Authors: Maden Malcolm , Hind Matthew
Published: January 2003

Retinoic acid (RA) is the biologically active metabolite of vitamin A. It is a low molecular weight, lipophilic molecule that acts on the nucleus to induce gene transcription. In amphibians and mammals, it induces the regeneration of several tissues and organs and these examples are reviewed here. RA induces the “super‐regeneration” of organs that can already regenerate such as the urodele amphibian limb by respecifying positional information in the limb. In organs that cannot normally regenerate such as the adult mammalian lung, RA induces the complete regeneration of alveoli that have been destroyed by various noxious treatments. In the mammalian central nervous system (CNS), which is another tissue that cannot regenerate, RA does not induce neurite outgrowth as it does in the embryonic CNS, because one of the retinoic acid receptors, RARβ2, is not up‐regulated. When RARβ2 is transfected into the adult spinal cord in vitro, then neurite outgrowth is stimulated. In all these cases, RA is required for the development of the organ, in the first place suggesting that the same gene pathways are likely to be used for both development and regeneration. This suggestion, therefore, might serve as a strategy for identifying potential tissue or organ targets that have the capacity to be stimulated to regenerate. Developmental Dynamics 226:237–244, 2003.© 2003 Wiley‐Liss, Inc.
Muscle regeneration in amphibians and mammals: Passing the torch
Authors: Carlson Bruce M.
Published: January 2003

Skeletal muscle in both amphibians and mammals possesses a high regenerative capacity. In amphibians, a muscle can regenerate in two distinct ways: as a tissue component of an entire regenerating limb (epimorphic regeneration) or as an isolated entity (tissue regeneration). In the absence of epimorphic regenerative ability, mammals can regenerate muscles only by the tissue mode. This review focuses principally on the regeneration of entire muscles and covers what is known and what remains to be elucidated about fundamental mechanisms underlying muscle regeneration at this level. Developmental Dynamics 226:167–181, 2003. © 2003 Wiley‐Liss, Inc.
Eye regeneration at the molecular age
Authors: Rio‐Tsonis Katia Del , Tsonis Panagiotis A.
Published: January 2003

Eye tissues such as the lens and the retina possess remarkable regenerative abilities. In amphibians, a complete lens can be regenerated after lentectomy. The process is a classic example of transdifferentiation of one cell type to another. Likewise, retina can be regenerated, but the strategy used to replace the damaged retina differs, depending on the animal system and the age of the animal. Retina can be regenerated by transdifferentiation or by the use of stem cells. In this review, we present a synthesis on the regenerative capacity of eye tissues in different animals with emphasis on the strategy and the molecules involved. In addition, we stress the place of this field at the molecular age and the importance of the recent technologic advances. Developmental Dynamics 226:211–224, 2003. © 2003 Wiley‐Liss, Inc.
Head regeneration in Hydra
Authors: Bode Hans R.
Published: January 2003

Hydra, a primitive metazoan, has a simple structure consisting of a head, body column, and foot aligned along a single oral–aboral axis. The body column has a high capacity for regeneration of both the head and foot. Because of the tissue dynamics that take place in adult Hydra, the processes governing axial patterning are continuously active to maintain the form of the animal. Regeneration in hydra is morphallactic and closely related to these axial patterning processes. As might be expected, analysis at the molecular level indicates that the same set of genes are involved in head regeneration and the maintenance of the head in the context of the tissue dynamics of the adult. The genes analyzed so far play roles in axial patterning processes in bilaterians. Developmental Dynamics 226:225–236, 2003. © 2003 Wiley‐Liss, Inc.