bluuebunny/crossref_metadata_2025 huggingface dataset:
AP‐2 and HNK‐1 define distinct populations of cranial neural crest cells
Authors: Minarcik J.C. , Golden J.A.
Published: December 2004

Structured Abstract

Authors – Minarcik JC, Golden JA

Objective – To determine if distinct populations of cranial neural crest cells (CNCC) exist by characterization of their divergent gene expression patterns.

Design – Identification of unique populations of CNCC was determined by a combination of lineage and immunohistochemical analyses.

Setting – Department of Pathology, Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, Philadelphia, PA 19104.

Results – We found antibodies of two proteins previously described as identifying all CNCC, label three populations of CNCC at specific time‐points. Furthermore, the activating protein 2 (AP‐2) expressing CNCC become neural or mesenchymal NCC derivatives whereas the HNK‐1 labeled cells do not participate in the mesenchymal lineage.

Conclusion – These data provide molecular markers for unique CNCC fates and thus will be invaluable in the characterizing of craniofacial anomalies related to defects in NCCS. In addition, our data suggest AP‐2 may function in determining the unique mesenchymal fate of CNCCs.
Orthodontic treatment of a case of Becker muscular dystrophy
Authors: Suda N. , Matsuda A. , Yoda S. , Ishizaki T. , Higashibori N. , Kim F. , Otani‐Saito K. , Ohyama K.
Published: December 2004

Becker muscular dystrophy, similar to Duchenne muscular dystrophy, is a X‐chromosomal linked anomaly characterized by progressive muscle wasting and weakness. Duchenne‐type is known to have severe openbite with a steep mandibular plane, but there are no studies that describe the occlusal and skeletal patterns of the Becker‐type. Here, we report the orthodontic treatment of a Becker muscular dystrophy patient. In the correction of his severe skeletal open bite general anesthesia or orthognathic surgery was not an option. Multiloop edgewise archwires were employed for orthodontic treatment. After 3 years and 8 months the open bite was corrected. During the retention period contact between the anterior teeth was maintained 8 months after active treatment despite a marked relapse tendency.
Stress Analysis by X-Ray Diffraction
Authors: Barrett C. S. , Gensamer M.
Published: December 2004

A mathematical analysis is presented for the problem of determining stresses in a metal by x-ray diffraction. The treatment is a general one, including as special cases the various methods for the determination of uniaxial stresses or the sum of two principal stresses in the plane of the metal surface. The analysis is extended to the problem of determining the two principal surface stresses individually. Methods are proposed by which these stresses may be determined with an accuracy calculated to be of the order of 1300 lbs./in.2 for iron and 320 lbs./in.2 for duralumin, under the best conditions. Camera design, exposure technique, and the applicability of the method to practical problems are discussed.
Quasi-Holonomic Dynamical Systems
Authors: Kron Gabriel
Published: December 2004

When a dynamical system contains both mechanical and electromagnetic energies, the dynamical equations assume special forms. It is shown that when the dynamical system is nonholonomic, or when it is holonomic but is referred to nonholonomic reference axes, the equations still have the same form as those of a holonomic dynamical system and can be solved as such without any auxiliary equations. Following a suggestion of Lorentz, such dynamical systems are called here ``quasi-holonomic'' dynamical systems. Because of the special form of the equations, their development in tensor notation allows the introduction of concepts from the absolute calculus that apparently have not been hitherto applied in classical dynamics. It is shown here that the equation of motion of quasi-holonomic systems in tensor symbolism may be interpreted as specifying the trajectory of a point moving in an (n-dimensional) non-Riemannian space, referred to holonomic or nonholonomic reference axes. When the field equations of Maxwell in tensor form are formulated for the electromagnetic part of the quasi-holonomic system, it is found that the electromagnetic field must be expressed in terms of its components along an orthogonal ennuple, the field lying in a local Euclidean space, tangent to the underlying non-Riemannian space. By the use of such a nonholonomic reference frame the dynamical equations of Lagrange and the field equations of Maxwell are correlated. The equations show formal analogies with those of the five-dimensional unified field theory of relativity dynamics, where combined electromagnetic and gravitational systems are analyzed. Practical examples of quasi-holonomic systems are the numerous types of rotating electrical machinery used in industry.
The Thermal Conductivity of Tungsten
Authors: Michels Walter C. , Cox Martha
Published: December 2004

The theory of the heat losses from an electrically heated wire, as given by Roberts and Kannuluik, has been extended to include a wire supported by springs. The results obtained have been used in a measurement of the thermal conductivity of commercial tungsten wire in the temperature range from 78°K to 273°K. There are definite indications that the Wiedemann-Franz law breaks down badly in this region.
Polarization Impedance at Low Frequencies
Authors: Murdock C. C. , Zimmerman E. E.
Published: December 2004

The polarization capacity of a Pt–H2SO4–Pt electrolytic cell of concentration 0.25 N has been studied using alternating currents ranging in frequency from 0.05 to 3500 cycles per second and using aperiodic currents whose time constants range from 0.15 to 1.5 seconds. The empirical law, C=13.6f−m, is found to hold throughout the frequency range with m=0.11. The angle Ψ by which the current fails of quadrature with the polarization is constant within the accuracy of measurement and is in agreement with the Fricke relation, Ψ=πm/2. The capacity as measured by aperiodic currents is found to increase slightly with the time constant. It is shown by a Fourier series expansion that if the alternating current results are correct, the aperiodic decay current is approximately exponential during the early part of the decay and that the measured polarization capacity is approximately proportional to the mth power of the time constant. The experimental data are in agreement with this conclusion.
Convergence behavior of the density-matrix renormalization group algorithm for optimized orbital orderings
Authors: Moritz Gerrit , Hess Bernd Artur , Reiher Markus
Published: December 2004

The density-matrix renormalization group algorithm has emerged as a promising new method in ab initio quantum chemistry. However, many problems still need to be solved before this method can be applied routinely. At the start of such a calculation, the orbitals originating from a preceding quantum chemical calculation must be placed in a specific order on a one-dimensional lattice. This ordering affects the convergence of the density-matrix renormalization group iterations significantly. In this paper, we present two approaches to obtain optimized orderings of the orbitals. First, we use a genetic algorithm to optimize the ordering with respect to a low total electronic energy obtained at a predefined stage of the density-matrix renormalization group algorithm with a given number of total states kept. In addition to that, we derive orderings from the one- and two-electron integrals of our test system. This test molecule is the chromium dimer, which is known to possess a complicated electronic structure. For this molecule, we have carried out calculations for the various orbital orderings obtained. The convergence behavior of the density-matrix renormalization group iterations is discussed in detail.
A nonadditive methanol force field: Bulk liquid and liquid-vapor interfacial properties via molecular dynamics simulations using a fluctuating charge model
Authors: Patel Sandeep , Brooks Charles L.
Published: December 2004

We study the bulk and interfacial properties of methanol via molecular dynamics simulations using a CHARMM (Chemistry at HARvard Molecular Mechanics) fluctuating charge force field. We discuss the parametrization of the electrostatic model as part of the ongoing CHARMM development for polarizable protein force fields. The bulk liquid properties are in agreement with available experimental data and competitive with existing fixed-charge and polarizable force fields. The liquid density and vaporization enthalpy are determined to be 0.809 g/cm3 and 8.9 kcal/mol compared to the experimental values of 0.787 g/cm3 and 8.94 kcal/mol, respectively. The liquid structure as indicated by radial distribution functions is in keeping with the most recent neutron diffraction results; the force field shows a slightly more ordered liquid, necessarily arising from the enhanced condensed phase electrostatics (as evidenced by an induced liquid phase dipole moment of 0.7 D), although the average coordination with two neighboring molecules is consistent with the experimental diffraction study as well as with recent density functional molecular dynamics calculations. The predicted surface tension of 19.66±1.03 dyn/cm is slightly lower than the experimental value of 22.6 dyn/cm, but still competitive with classical force fields. The interface demonstrates the preferential molecular orientation of molecules as observed via nonlinear optical spectroscopic methods. Finally, via canonical molecular dynamics simulations, we assess the model’s ability to reproduce the vapor-liquid equilibrium from 298 to 423 K, the simulation data then used to obtain estimates of the model’s critical temperature and density. The model predicts a critical temperature of 470.1 K and critical density of 0.312 g/cm3 compared to the experimental values of 512.65 K and 0.279 g/cm3, respectively. The model underestimates the critical temperature by 8% and overestimates the critical density by 10%, and in this sense is roughly equivalent to the underlying fixed-charge CHARMM22 force field.
Structure of strongly interacting polyelectrolyte diblock copolymer micelles
Authors: Korobko A. V. , Jesse W. , Lapp A. , Egelhaaf S. U. , van der Maarel J. R. C.
Published: December 2004

The structure of spherical micelles of the diblock poly(styrene-block-acrylic acid) [PS-b-PA] copolymer in water was investigated up to concentrations where the polyelectrolyte coronal layers have to shrink and/or interpenetrate in order to accommodate the micelles in the increasingly crowded volume. We obtained the partial structure factors pertaining to the core and corona density correlations with small angle neutron scattering and contrast matching in the water. The counterion structure factor was obtained with small angle x-ray scattering (SAXS) with a synchrotron radiation source. Furthermore, we have measured the flow curves and dynamic visco-elastic moduli. The functionality of the micelles is fixed with a 9 nm diameter PS core and a corona formed by around 100 PA arms. As shown by the SAXS intensities, the counterions are distributed in the coronal layer with the same density profile as the corona forming segments. Irrespective ionic strength and micelle charge, the corona shrinks with increasing packing fraction. At high charge and minimal screening conditions, the polyelectrolyte chains remain almost fully stretched and they interdigitate once the volume fraction exceeds the critical value 0.53±0.02. Interpenetration of the polyelectrolyte brushes also controls the fluid rheology: The viscosity increases by three orders of magnitude and the parallel frequency scaling behavior of the dynamic moduli suggests the formation of a physical gel. In excess salt, the coronal layers are less extended and they do not interpenetrate in the present concentration range.
Study of thermodynamic stabilities of polytypes of n-C36H74 by solubility measurements and incoherent inelastic neutron scattering
Authors: Kubota Hideki , Kaneko Fumitoshi , Kawaguchi Tatsuya
Published: December 2004

The thermodynamic properties of the two polytypes of n-hexatriacontane (n-C36H74), single-layered structure Mon and double-layered structure Orth II have been investigated by means of solubility measurements and incoherent inelastic neutron scattering. The solubility measurements reveal that Orth II is more stable than Mon by 1.2 kJ/mol because of the advantage of larger entropy. The neutron scattering measurements show that the vibrational modes of Orth II shift to the lower frequencies compared with those of Mon in the frequency region below 120 cm−1. The advantage of Orth II in vibrational entropy due to the low-frequency shifts is estimated to be 9.6 J K−1/mol at 288 K under the harmonic approximation, which nearly agrees with the entropy difference of 6.8 J K−1/mol between Mon and Orth II determined by solubility measurements. These results suggest that the difference in vibrational entropy due to low-frequency modes mainly contributes to the relative thermodynamic stabilities of polytypic structures of long-chain compounds. From the frequency of methyl torsional mode, it is suggested that the cohesive force at the lamellar interface is stronger in Mon than in Orth II.
Kinetics of shrinking of polymer gels induced by ultracentrifugal fields
Authors: Urayama Kenji , Okada Shinichi , Nosaka Shoji , Watanabe Hiroshi , Takigawa Toshikazu
Published: December 2004

The kinetics of the shrinking of polymer gels induced by ultracentrifugal fields is investigated. A theory is proposed to describe the diffusion process of polymer networks under centrifugal fields. The initial shrinking rate is proportional to the ratio of the centrifugal force to the frictional force of networks. The shrinking attains the stationary state as a result of the balance between the centrifugal force and the swelling force of networks. The characteristic time for shrinking is of the order of a2/D where a and D are the stationary displacement and diffusion constant, respectively. We also present the experimental data for the shrinking of the poly(acrylamide) (PAAm) gels under ultracentrifugal fields. The shrinkage increases linearly with time in the initial stage whereas it reaches the steady state in the long time limit as expected by the theory. Each of longitudinal elastic modulus and friction coefficient of the PAAm gels is evaluated from the data on the basis of the theory.
Using optical tweezers to relate the chemical and mechanical cross-bridge cycles
Authors: Holmes K. C. , Trentham D. R. , Simmons R. , Steffen Walter , Sleep John
Published: December 2004

In most current models of muscle contraction there are two translational steps, the working stroke, whereby an attached myosin cross–bridge moves relative to the actin filament, and the repriming step, in which the cross–bridge returns to its original orientation. The development of single molecule methods has allowed a more detailed investigation of the relationship of these mechanical steps to the underlying
biochemistry. In the normal adenosine triphosphate cycle, myosin·adenosine diphosphate·phosphate (M·ADP·P
i
) binds to actin and moves it by
ca
. 5 nm on average before the formation of the end product,
the rigor actomyosin state. All the other product–like intermediate states tested were found to give no net movement indicating that M·ADP·P
i
alone binds in a pre–force state.Myosin states with bound, unhydrolysed nucleoside triphosphates also give no net movement, indicating that these must also bind in a post–force conformation and that the repriming, post– to pre–transition during the forward cycle must take place while the myosin is dissociated from actin. These observations fit in well with the structural model in which the working stroke is aligned to the opening of the switch 2 element of the ATPase site.
Liberation Theology After the End of History: An Exchange
Authors: Volf Miroslav
Published: December 2004

Book Reviewed in this article:

Daniel M. Bell, Liberation Theology After the End of History: The Refusal to Cease Suffering
The price of natural gas
Authors: Bakhtiari A.M. Samsam
Published: December 2004

Natural gas used to be a relatively Cheap primary energy source, always at a discount to crude oil (on a comparative British thermal unit basis). It gradually evolved into a major resource during the 20th century — reaching a 24 per cent share of global primary energy in 1999.

In the year 2000, natural gas prices in the USA rose to unheard‐of highs of $10/million Btu, ushering in a new era, with natural gas at a 120 per cent premium to crude oil. This clearly was a watershed for gas, somehow similar to the 1973‐74 watershed for oil prices. And similarly, any return to the status quo‐ante looks rather improbable, although a number of experts (alongside the International Energy Agency) still believe the 2000 price ‘spike’ to have been “only transitory”

The consequences of higher gas prices (at a level equal to crude oil prices on a Btu basis) will be multifaceted and momentous, altering habits and uses in downstream industries and economic sectors, as well as providing added income for major gas‐exporters, such as Russia, Canada and Algeria.

Another potential consequence of the 2000 watershed might be to propel US standard prices (such as the ‘Henry Hub’ spot) to international status and gas price‐setter, as the ‘WTI spot’ became an “international benchmark” for crude oils in the post‐1993 era.

For the time being, the equality of gas and oil prices has become the new norm; but, in the longer term, a discount of crude oil relative to natural gas might be envisaged, as the latter is a cleaner fuel and emits less carbon dioxide when used.
Is I Guaranteed to Refer?
Authors: De Gaynesford Maximilian
Published: December 2004

Abstract: One claim about I, regularly made and almost universally endorsed, is that uses of the term are logically guaranteed to refer successfully (if they refer at all). The claim is only rarely formulated perspicuously or argued for. Such obscurity helps disguise the fact that those who profess to advance the claim actually turn out to support not a logical guarantee at all but merely high security through fortunate coincidence. This is not surprising. For we have no good reason to accept the claim – granted, any use of I is apt to refer successfully; but that can be explained by pragmatic features of its use. And we have some reason to reject the claim – it is notoriously difficult to see how genuine reference and guaranteed success do not exclude each other when considered as properties of the logic of any term.
Victim‐Centered Retributivism
Authors: Lippke Richard L.
Published: December 2004

Abstract: Critics charge that retributivists fail to show why the state should concern itself with ensuring that criminal offenders are punished in accordance with their ill deserts. Drawing on the notion that the state should attempt to equalize the realization of the interests designated by rights, it is argued that legal punishment restores the equality of condition, disrupted by criminal conduct, that all citizens are entitled to. While this equality of condition might be restored in various ways, it is argued that the imposition of punitive losses is the most appropriate way to restore it in most cases. An account of the ill deserts of offenders, as a function of the harms their crimes produce and the extent of their culpability for those harms, is briefly elaborated.
The Model Theoretic Argument, Indirect Realism, and the Causal Theory of Reference Objection
Authors: Reynolds Steven L.
Published: December 2004

Abstract: Hilary Putnam has reformulated his model‐theoretic argument as an argument against indirect realism in the philosophy of perception. This new argument is reviewed and defended. Putnam's new focus on philosophical theories of perception (instead of metaphysical realism) makes better sense of his previous responses to the objection from the causal theory of reference. It is argued that the model‐theoretic argument can also be construed as an argument that holders of a causal theory of reference should adopt direct realism in the philosophy of perception.
Insights into the Management of Challenging Behaviour in School
Authors: Lines Dennis
Published: December 2004

This paper argues that the pastoral care systems of today need to be modernized and that, in particular, there is a need to adopt a more proactive approach to the management of challenging behaviour. The author argues that there is a need to anticipate and develop an approach to disruptive behaviour. He offers a framework for change and explores all aspects of this including interventions with students.
Selection Incentives in a Performance‐Based Contracting System
Authors: Shen Yujing
Published: December 2004

Objective. To investigate whether a performance‐based contracting (PBC) system provides incentives for nonprofit providers of substance abuse treatment to select less severe clients into treatment.

Data Sources. The Maine Addiction Treatment System (MATS) standardized admission and discharge data provided by the Maine Office of Substance Abuse (OSA) for fiscal years 1991–1995, provides demographic, substance abuse, and social functional information on clients of programs receiving public funding.

Study Design. We focused on OSA clients (i.e., those patients whose treatment cost was covered by the funding from OSA) and Medicaid clients in outpatient programs. Clients were identified as being “most severe” or not. We compared the likelihood for OSA clients to be “most severe” before PBC and after PBC using Medicaid clients as the control. Multivariate regression analysis was employed to predict the marginal effect of PBC on the probability of OSA clients' being most severe after controlling for other factors.

Principal Findings. The percentage of OSA outpatient clients classified as most severe users dropped by 7 percent (p<=0.001) after the innovation of performance‐based contracting, compared to the increase of 2 percent for Medicaid clients. The regression results also showed that PBC had a significantly negative marginal effect on the probability of OSA clients being most severe.

Conclusions. Performance‐based contracting gave providers of substance abuse treatment financial incentives to treat less severe OSA clients in order to improve their performance outcomes. Fewer OSA clients with the greatest severity were treated in outpatient programs with the implementation of PBC. These results suggest that regulators, or payers, should evaluate programs comprehensively taking this type of selection behavior into consideration.
Medicare Breast Surgery Fees and Treatment Received by Older Women with Localized Breast Cancer
Authors: Hadley Jack , Mandelblatt Jeanne S. , Mitchell Jean M. , Weeks Jane C. , Guadagnoli Edward , Hwang Yi‐Ting
Published: December 2004

Objective. To determine whether area‐level Medicare physician fees for mastectomy and breast conserving surgery were associated with treatment received by Medicare beneficiaries with localized breast cancer and to compare these results with an earlier analysis conducted using small areas (three‐digit zip codes) as the unit of observation.

Data Source. Medicare claims and physician survey data for a national sample of elderly (aged 67 or older) Medicare beneficiaries with localized breast cancer treated in 1994 (unweighted n=1,787).

Study Design. Multinomial logistic regression analysis was used to estimate a model of treatment received as a function of Medicare fees, controlling for other area economic factors, patient demographic and clinical characteristics, physician experience, and region.

Principal Findings. In 1994, average Medicare fees (adjusted for the effects of modifiers and procedure mix) for mastectomy (MST) and breast conserving surgery (BCS) were $904 and $305, respectively. Holding other fees and factors fixed, a 10 percent increase in the BCS fee increased the odds of breast conserving surgery with radiation therapy relative to mastectomy to 1.34 (p=0.02), while a 10 percent decrease in the MST fee increased the odds of breast conserving surgery with radiation therapy to 1.86 (p<0.01).

Conclusions. Among older women with localized breast cancer, financial incentives appear to influence the use of mastectomy and breast conserving surgery with radiation therapy. This finding is consistent with the hypothesis that physicians are responsive to financial incentives when the alternative procedures have clinically equivalent outcomes and the patient's clinical condition does not dominate the treatment choice. We also find that the fee effects derived from this analysis of individual data with more precise measurement of both diagnosis and treatment are qualitatively similar to the results of the small‐area analysis. This suggests that the earlier study was not severely affected by ecological bias or other data limitations inherent in Medicare claims data.
Economic Expansion Is a Major Determinant of Physician Supply and Utilization
Authors: Cooper Richard A. , Getzen Thomas E. , Laud Prakash
Published: December 2004

Objective. To assess the relationship between levels of economic development and the supply and utilization of physicians.

Data Sources. Data were obtained from the American Medical Association, American Osteopathic Association, Organization for Economic Cooperation and Development (OECD), Bureau of Health Professions, Bureau of Labor Statistics, Bureau of Economic Analysis, Census Bureau, Health Care Financing Administration, and historical sources.

Study Design. Economic development, expressed as real per capita gross domestic product (GDP) or personal income, was correlated with per capita health care labor and physician supply within countries and states over periods of time spanning 25–70 years and across countries, states, and metropolitan statistical areas (MSAs) at multiple points in time over periods of up to 30 years. Longitudinal data were analyzed in four complementary ways: (1) simple univariate regressions; (2) regressions in which temporal trends were partialled out; (3) time series comparing percentage differences across segments of time; and (4) a bivariate Granger causality test. Cross‐sectional data were assessed at multiple time points by means of univariate regression analyses.

Principal Findings Under each analytic scenario, physician supply correlated with differences in GDP or personal income. Longitudinal correlations were associated with temporal lags of approximately 5 years for health employment and 10 years for changes in physician supply. The magnitude of changes in per capita physician supply in the United States was equivalent to differences of approximately 0.75 percent for each 1.0 percent difference in GDP. The greatest effects of economic expansion were on the medical specialties, whereas the surgical and hospital‐based specialties were affected to a lesser degree, and levels of economic expansion had little influence on family/general practice.

Conclusions Economic expansion has a strong, lagged relationship with changes in physician supply. This suggests that economic projections could serve as a gauge for projecting the future utilization of physician services.
Learning Language for Work and Life: The Linguistic Socialization of Immigrant Canadians Seeking Careers in Healthcare
Authors: Duff Patricia A. , Wong Ping , Early Margaret
Published: December 2004

This article discusses research on ESL for the workplace, identifying gaps in the existing literature and promising directions for new explorations. A qualitative study was conducted in one type of program for immigrant women and men in Western Canada seeking to become long–term resident care aides or home support workers. The study examined the linguistic and social processes at work in the education and integration of immigrant ESL speakers into the workforce and the broader community; the issues participants in such programs face; and the insights that can be gleaned for understanding language socialization in this context. Of particular interest was the contrast observed in one such program between the focus on medical and general English language proficiency, as well as nursing skills, and the actual communication requirements within institutions with large numbers of staff and patients who do not speak English, and who, in the case of the elderly, may also face communication difficulties associated with ageing, illness, and disability. Implications for future research and curriculum development are discussed.
Expression of occludin in human rectal carcinoid tumours as a possible marker for glandular differentiation
Authors: Tokunaga Y , Tobioka H , Isomura H , Kokai Y , Sawada N
Published: December 2004

Aims:  To examine whether or not the tight junction‐associated transmembrane protein occludin is expressed in rosette or gland‐like structures in human rectal carcinoid tumours. The tight junction is crucial for the formation and maintenance of organized tubular structures in glandular epithelia. Previous studies have reported the presence of glandular structures in carcinoid tumours, though they are not believed to arise from glandular epithelium.

Methods and results:  The expression profiles of occludin in 40 carcinoid tumours were examined immunohistochemically, using an anti‐occludin monoclonal antibody. In eight (20%) samples of typical carcinoid tumours, a small number of rosette‐like tubular structures outlined by occludin were detected.

Conclusions:  Tight junction‐associated molecules, including occludin, are thought to be one of the most characteristic structural markers of polarized glandular structures. The results of the present study provide supportive evidence that carcinoid tumour cells are capable of glandular differentiation.
Expression of Tie‐1 and 2 receptors, and angiopoietin‐1, 2 and 4 in gastric carcinoma; immunohistochemical analyses and correlation with clinicopathological factors
Authors: Nakayama T , Yoshizaki A , Kawahara N , Ohtsuru A , Wen C Y , Fukuda E , Nakashima M , Sekine I
Published: December 2004

Aims:  There is strong evidence that tyrosine kinases are involved in the regulation of tumour progression, cellular growth and differentiation. Recently, many kinds of tyrosine kinase receptors have been reported, and among them Tie‐1 and 2 constitute a major class. Angiopoietin (Ang)‐1 is known as a ligand of the Tie‐2 tyrosine kinase receptor. The aim of this study was to determine the expression profile of Tie‐1 and 2 and Ang‐1, 2 and 4 in gastric adenocarcinoma.

Methods and results:  Eighty‐nine cases of surgically resected human gastric adenocarcinoma were studied by immunohistochemistry. Of these, 60 (67.4%), 61 (68.5%), 69 (77.5%), 75 (84.3%), and 47 cases (52.8%) showed positive staining in the cytoplasm of carcinoma cells for the Tie‐1 and 2 and Ang‐1, 2 and 4 proteins, respectively. The expression of Ties and Angs was significantly correlated with several type of histological differentiation and several clinicopathological factors.

Conclusions:  Ties and Angs were highly expressed in human gastric adenocarcinoma cells. These findings suggest that the Tie–Ang receptor–ligand complex is one of the factors involved in the cellular differentiation and progression of human gastric adenocarcinoma.
Condyloma acuminatum and condyloma‐like lesions of the oral cavity: a study of 11 cases with an intraductal component
Authors: Henley J D , Summerlin D‐J , Tomich C E
Published: December 2004

Aims:  We studied the clinicopathological features of 11 condyloma and condyloma‐like lesions of the oral cavity with an unusual mixed pattern of exophytic and intraductal growth. The latter manifest as involvement of minor salivary gland ducts by the proliferative squamous lesions. This pattern of ductal involvement has not been previously described in oral condyloma.

Methods and results:  The clinical history was available for nine patients ranging in age from 17 to 73 years. Two were female and seven male. The buccal mucosa (five cases) was the most common site of occurrence, followed by the floor of mouth (two cases), lingual frenum (two cases), and hard palate (one case). All lesions exhibited exophytic and intraductal growth. The latter manifested itself as extension of the lesions into the excretory ducts of minor salivary glands. Underlying minor salivary glands, present in many of the excisional biopsy specimens, typically showed changes of obstructive atrophy. The exophytic components of all cases exhibited some degree of parakeratosis, and cryptic invaginations of parakeratin were typically present. Koilocytes were present in seven lesions and were equivocal in four. Mucous cells were present in the intraductal component of all cases and the intraductal component was never keratinized, but often papillary. A mild stromal‐based, lymphocytic host response was present in three. A variably prominent neutrophilic infiltrate was present in the exophytic component of eight. Dysplasia was not present in any case. Five of 11 cases were positive with anti‐human papillomavirus (HPV) and two of 11 cases were positive for in‐situ hybridization probes directed against HPV 6/11. All cases were negative for HPV 16/18 and 13/33/35.

Conclusions:  Oral condyloma acuminatum may involve the excretory ducts of minor salivary glands. The diagnosis of oral condyloma acuminatum is difficult, as these lesions share considerable histological overlap with squamous papilloma. Finally, the relationship between these two lesions is incompletely understood.
Antigen specificity of semi‐invariant CD1d‐restricted T cell receptors: The best of both worlds?
Authors: Gumperz Jenny E
Published: December 2004

T lymphocytes are characterized by the use of structurally diverse TCR. The discovery of subsets of canonical T cells that have structurally homogeneous TCR presents an enigma: What antigens do these T cells recognize, and how does their antigen specificity relate to their functions? One subset of canonical T cells is restricted by CD1d, a non‐classical antigen presenting molecule that presents lipids and glycolipids. Canonical CD1d‐restricted T cells have semi‐invariant TCR consisting of an invariantly rearranged TCRα chain, paired with diversely rearranged TCRβ chains. Most respond strongly to the unusual glycolipid α‐galactosylceramide (α‐GalCer), and can also respond to cellular antigens presented by CD1d. Mounting evidence indicates that α‐GalCer responsive T cells are heterogeneous in their reactivities to cellular antigens, suggesting that an individual semi‐invariant TCR may be capable of recognizing more than one ligand. Recent crystal structures of CD1b molecules with three different bound lipids indicate that the antigenic features of lipids may be localized over a smaller area than those of peptides, and that the positioning of the polar head group can vary substantially. A model that explains how CD1d‐restricted T cells could possess both conserved and heterogeneous antigen specificities, is that different lipid antigens may interact with distinct areas of a TCR due to differences in the positioning of the polar head group. Hence, canonical CD1d‐restricted TCR could recognize conserved antigens via the invariant TCRα chain, and have diverse antigen specificities that are conferred by their individual TCRβ chains.
The Third Way: Progress on pathways of antigen processing and presentation by CD1
Authors: Lawton Anna P , Kronenberg Mitchell
Published: December 2004

CD1 proteins are a third family of antigen presenting molecules that bind bacterial and autologous lipid antigens for presentation to T cells. With the solution of the crystal structures of several complexes of CD1 molecules with lipids, a greater appreciation has been gained of the adaptability of CD1 in binding lipid antigens with diverse structural features. Biochemical studies of the interactions between the TCR and CD1‐lipid complexes have revealed striking contrasts with TCR that bind to peptides presented by MHC‐encoded class I and class II molecules. The sphingolipid activating proteins (SAP) have recently been found to facilitate the transfer of lipid antigens onto CD1 molecules. This helps to provide an explanation as to how the thermodynamic barrier, caused by loading hydrophobic lipid antigens in a hydrophilic environment, can be overcome. Mechanisms of CD1 endosomal trafficking are being delineated, including the means by which adaptor proteins induce the localization of some types of CD1 molecules to lysosomes, where they bind antigens. Unlike MHC class I and class II proteins, specialized molecules that function solely in chaperoning CD1 molecules, or in facilitating their antigen loading, have not been found. This suggests that the CD1 antigen presenting system, which diverged early in vertebrate evolution from MHC antigen presenting molecules, is a simpler system with a character closer to the primordial antigen presenting function.
Cystic fibrohistiocytic tumours presenting in the lung: primary or metastatic disease?
Authors: Osborn M , Mandys V , Beddow E , Ladas G , Florio R , Sheppard M N , Fisher C , Bell S W , Travis W D , Nicholson A G
Published: December 2004

Aims:  Cystic fibrohistiocytic tumour of the lung is a rare proliferative process. Its histogenesis is uncertain, but evidence suggests that some cases represent metastatic disease from apparently indolent skin lesions, namely cellular fibrous histiocytomas. This study presents four cases and reviews the literature concerning this pattern of disease and its aetiology.

Methods and results:  All patients were male (age range 35–54 years). Two presented with recurrent haemoptysis. Two cases had histories of cutaneous fibrohistiocytic lesions in the chest wall, excised 10 and 23 years prior to presentation with lung disease. Imaging data showed multiple bilateral cystic lung lesions in all four patients with nodular cavitating opacities seen on high‐resolution computed tomography scans. Microscopy showed variably dilated thin‐walled cystic airspaces lined by cuboidal epithelium and an underlying layer of mildly pleomorphic spindle cells with slightly wavy morphology and storiform architecture, admixed with inflammatory cells. Tumour cells stained for CD68 in three of four cases. All cases were negative for CD34. All patients were alive with disease, although one required pneumonectomy for intractable haemoptysis.

Conclusion:  This study and a review of published cases show that the majority of cystic fibrohistiocytic tumours of the lung probably represent metastases from cellular fibrous histiocytomas. However, rare cases may be either primary in origin or the primary site remains occult; the term cystic fibrohistiocytic tumour remains appropriate for such cases.
Lymph node reticulum cell neoplasm with progression into cytokeratin‐positive interstitial reticulum cell (CIRC) sarcoma: a case study
Authors: Lucioni M , Boveri E , Rosso R , Benazzo M , Necchi V , Danova M , Incardona P , Franco C , Viglio A , Riboni R , Lazzarino M , Magrini U , Canevari A , Paulli M
Published: December 2004

Aims:  To detail on sequential biopsies the morphological and immunohistochemical features of a case of primary lymph nodal fibroblastic reticulum cell (FBRC) tumour which progressed into a clinically aggressive cytokeratin‐positive interstitial reticulum cell (CIRC) sarcoma.

Methods and results:  A 70‐year‐old female underwent surgical excision of an enlarged submandibular lymph node. The nodal architecture was effaced by a neoplastic proliferation of medium to large cells, round to oval to spindle in shape, growing in a storiform pattern. The tumour stained for vimentin, CD68, factor XIIIa, α1‐antitrypsin, fascin and actin. Dendritic and endothelial cell markers were negative. A diagnosis of FBRC tumour was made by combining pathological and clinical data. The patient received no therapy but 5 months later the tumour relapsed, exhibiting a deceptively pleomorphic cytology, phenotypic changes (strong cytokeratin positivity), intense p53 expression and aggressive clinical course with fatal outcome. In‐situ hybridization for Epstein–Barr virus was negative.

Conclusions:  We speculate that the morphological changes and p53 expression of the relapsing neoplasm might reflect tumour cell dedifferentiation, in keeping with the aggressive clinical course. The intense p53 expression suggests that this oncoprotein might also play a role in reticulum cell tumorigenesis.
Cathepsin B, D and K expression in adamantinomatous craniopharyngiomas relates to their levels of differentiation as determined by the patterns of retinoic acid receptor expression
Authors: Lubansu A , Ruchoux M‐M , Brotchi J , Salmon I , Kiss R , Lefranc F
Published: December 2004

Aims:  To investigate the potential predictive value of cathepsins B, D and K in a series of 51 adamantinomatous craniopharyngiomas. While almost always benign, craniopharyngiomas exhibit a high propensity to recur postsurgically and biological markers are therefore needed to predict their recurrence. We have previously demonstrated the potential predictive value of retinoic acid receptors (RARs) (Lefranc et al., J. Neurosurg. 2003; 98; 145–153).

Methods and results:  Computer‐assisted microscopy was used to determine quantitatively the immunohistochemical levels of expression of the α, β and γ RAR subtypes and cathepsins B, D and K. The levels of expression of cathepsin D and of cathepsin B correlated significantly with the levels of expression of RARβ. The levels of expression of cathepsin K correlated significantly with the levels of expression of RARγ.

Conclusions:  Recurrent adamantinomatous craniopharyngiomas are characterized by low levels of RARβ and high levels of RARγ. The tendency to recurrence seems, at least partly, to relate to the fact that (i) craniopharyngiomas with low levels of RARβ express low levels of cathepsin D, and (ii) craniopharyngiomas with high levels of RARγ express high levels of cathepsin K.
Focal hyperplastic hepatocellular nodules in hepatic venous outflow obstruction: a clinicopathological study of four patients and 24 nodules
Authors: Ibarrola C , Castellano V M , Colina F
Published: December 2004

Aims : In hepatic venous outflow obstruction (Budd–Chiari syndrome), focal hepatocellular nodules are occasionally discovered showing variable morphology. These could be interpreted either as neoplastic (adenoma), regenerative (large regenerative nodule) or reactive to abnormal vasculature (focal nodular hyperplasia). The aim of this study was to investigate their histogenesis and to determine their morphological characteristics in order to provide diagnostic criteria.

Material and methods : Twenty‐four hepatocellular nodules were studied, which were found in three explanted livers and in one additional autopsied liver from four patients with Budd–Chiari syndrome. As controls, we employed three explanted livers without nodules from patients who also suffered from Budd–Chiari syndrome. We attempted to classify the nodules morphologically as either adenoma‐like, large regenerative nodule or focal nodular hyperplasia‐like, using criteria from the literature.

Results : Out of the four cases, we observed two nodules in each of two livers, five in the third one and up to 15 in the remaining one. The size of the nodules ranged from 4 to 25 mm. Eleven nodules could be categorized as large regenerative nodules (two of them with a central scar), seven as focal nodular hyperplasia‐like and six as adenoma‐like. Some large regenerative nodules showed proliferated arteries with muscular hyperplasia similar to that seen in focal nodular hyperplasia. In the individual livers we could find nodules of various categories. Patchy or diffuse monoacinar regeneration was seen in most cases (six out of seven cases) in the macroscopically non‐nodular liver parenchyma. In addition, thrombotic obstruction of portal vein branches was present in all except one of the nodular cases, but in none of the controls. Thus, it appears that portal venous obstructions are frequently, but not invariably associated with the development of nodules.

Conclusions : The hepatocellular nodules seen in livers from patients with Budd–Chiari syndrome share morphological characteristics with large regenerative nodules, focal nodular hyperplasia and hepatocellular adenomas. Their multiplicity, the existence of mixed lesions, the frequent hepatocellular regenerative background as well as the frequently associated portal venous obstructions suggest that these nodules are regenerative in nature and conditioned by an uneven blood perfusion throughout the liver. In their differential diagnosis, the clinicopathological context in which they occur is of paramount importance and should allow recognition that those resembling adenomas may not be true neoplasms.
Combined status of MUC1 mucin and surfactant apoprotein A expression can predict the outcome of patients with small‐size lung adenocarcinoma
Authors: Tsutsumida H , Goto M , Kitajima S , Kubota I , Hirotsu Y , Yonezawa S
Published: December 2004

Aim : Lung cancer is still a disease of high mortality, despite advanced diagnostic techniques. Here, we aim to report a unique method to predict the recurrence and outcome of patients with pulmonary adenocarcinomas.

Methods and results : Immunohistochemical expression of MUC1 mucin and surfactant apoprotein A (SP‐A) was examined in 185 cases of surgically removed lung adenocarcinomas of non‐bronchioloalveolar type smaller than 30 mm. Staining results were evaluated semiquantitatively, and the expression of MUC1 and SP‐A was compared in each case. There were 140/185 (76%) cases showing MUC1 expression higher than SP‐A expression (MUC1>SP‐A), and 45/185 (24%) cases showing MUC1 expression lower than or equal to SP‐A expression (MUC1≤SP‐A). Recurrence was observed in 24% (34/140) of the patients with a MUC1>SP‐A pattern, but in 7% (3/45) of the patients with a MUC1≤SP‐A pattern after the median observation period of 41 months (1–99 months) (P < 0.01). The MUC1>SP‐A group showed higher recurrence and worse survival than the MUC1≤SP‐A group by Kaplan–Meier's method (P < 0.01 and P < 0.005). Even in the patients with apparently favourable prognostic factors (well‐differentiated adenocarcinoma or no lymph node metastasis), recurrence and survival were different between the two groups.

Conclusions : A high MUC1/SP‐A ratio is strongly associated with a poor outcome in patients with small‐size lung adenocarcinoma.
Polymorphous low‐grade adenocarcinoma of the major salivary glands: report of three cases in an unusual location
Authors: Nagao T , Gaffey T A , Kay P A , Minato H , Serizawa H , Lewis J E
Published: December 2004

Aims : Polymorphous low‐grade adenocarcinoma (PLGA) is the second most common type of malignant neoplasm in minor salivary glands. Its origin in major salivary glands is considered exceedingly rare. Herein, we present three cases of de novo PLGA arising in major salivary glands.

Methods and results : Three cases of PLGA were identified in a large series of primary tumours of major salivary glands. We investigated their clinicopathological profiles, including immunohistochemical features. The three patients (two men and one woman) were 51, 65, and 79 years old. The tumours were 20–30 mm large; two were in the parotid gland and one in the submandibular gland. Histologically, all the tumours had a polymorphous architectural pattern showing predominantly solid, tubular, and cribriform features and invasive growth. Papillary areas were observed focally in two tumours and an ‘Indian‐file’ array in one. The tumour cells had a bland cytological appearance and low mitotic count. Two tumours showed perineural invasion. No preexisting pleomorphic adenoma component was identified. In all cases, tumour cells were positive for epithelial markers, S100 protein, and vimentin but negative for α‐smooth muscle actin, muscle‐specific actin, and glial fibrillary acidic protein. Proliferative activities assessed with the Ki67 labelling index were 4.3%, 7.1%, and 7.6%; no p53 overexpression was observed. Two patients had local recurrence, but none had metastasis or died of tumour.

Conclusions : PLGAs arising in major salivary glands and those in minor salivary glands have similar clinicopathological and immunohistochemical characteristics. It is important to recognize that PLGA can occur ab initio in the major salivary glands, although it is extremely rare.