bluuebunny/crossref_metadata_2025 huggingface dataset:
Microglia and the early phase of immune surveillance in the axotomized facial motor nucleus: Impaired microglial activation and lymphocyte recruitment but no effect on neuronal survival or axonal regeneration in macrophage‐colony stimulating factor‐deficient mice
Authors: Kalla Roger , Liu Zhiqiang , Xu Shengli , Koppius Andrea , Imai Yoshinori , Kloss Christian U.A. , Kohsaka Shinichi , Gschwendtner Andreas , Möller J. Carsten , Werner Alexander , Raivich Gennadij
Published: October 2004

Activation of microglia is among the first cellular changes in the injured CNS. However, little is known about their specific contribution to secondary damage or repair processes in neighboring neurons and nonneuronal cells or to the immune surveillance of the damaged tissue. Animal models with defective microglial response such as osteopetrosis provide an approach to explore these effects. Osteopetrosis (op) is an autosomal recessive mutation with a complete deficiency of the macrophage‐colony stimulating factor (MCSF; CSF‐1), an important mitogen for brain microglia. In the current study we examined the effects of this MCSF deficiency on the microglial reaction and the overall cellular response to nerve injury in the mouse axotomized facial motor nucleus. In the brain, MCSF receptor immunoreactivity was found only on microglia and was strongly up‐regulated following injury. MCSF deficiency led to a failure of microglia to show a normal increase in early activation markers (thrombospondin, MCSF receptor, αMβ2‐ and α5β1‐integrins), to spread on the surface of axotomized motoneurons, and to proliferate after injury. Early recruitment of CD3+ T‐lymphocytes to the facial nucleus 24 hours after injury was reduced by 60%. In contrast, the neuronal and astrocyte response was not affected. There was a normal increase in the neuropeptides calcitonin gene‐related peptide and galanin, neuronal c‐JUN, and NADPH‐diaphorase and a decrease in choline acetyltransferase and acetylcholinesterase. Astrocyte glial fibrillary acidic protein immunoreactivity also showed a normal increase. There was a normal influx of macrophages and granulocytes into the injured facial nerve. Synaptic stripping, neuronal survival, and speed of axonal regeneration were also not affected. The current results show a strong, selective effect of MCSF on the early activation of microglia and, indirectly, on lymphocyte recruitment. This early phase of microglial activation appears not to be involved in the process of repair following peripheral nerve injury. However, it is important in the initiation of inflammatory changes in the brain and in the interaction with the immune system. J. Comp. Neurol. 436:182–201, 2001. © 2001 Wiley‐Liss, Inc.
Cadherin expression by embryonic divisions and derived gray matter structures in the telencephalon of the chicken
Authors: Redies Christoph , Medina Loreta , Puelles Luis
Published: October 2004

The expression of three cadherins (cadherin‐6B, cadherin‐7, and R‐cadherin) was studied by immunohistochemistry in the telencephalon of chicken embryos at intermediate stages of development (11 and 15 days of incubation). Expression patterns were related to cytoarchitecture and to previously published data on functional connections and on the expression of gene regulatory proteins. Our results indicate that, like in other regions of the embryonic chicken brain, the expression of each cadherin is restricted to parts of embryonic divisions as well as to particular nuclei, areas or their subdivisions. The expression patterns are largely complementary with partial overlap. The regional expression of the cadherins respects the boundary between the pallium and the subpallium as well as between various pallial and subpallial subdivisions. Novel subdivisions were found in several telencephalic areas. For example, subjacent to the hyperstriatum, the neostriatum contains multiple islands of cells with a profile of cadherin expression that differs from the surrounding matrix (“island fields”). Moreover, the expression of each cadherin is apparently associated with parts of intratelencephalic neural circuits and of thalamopallial and basal ganglia pathways. These results support a role for cadherins in the aggregation and differentiation of gray matter structures within embryonic brain divisions. The cadherin immunostaining patterns are interpreted in the context of a recently proposed divisional scheme of the avian pallium that postulates medial, dorsal, lateral, and ventral divisions as complete radial histogenetic units (Puelles et al. [2000]). J. Comp. Neurol. 438:253–285, 2001. © 2001 Wiley‐Liss, Inc.
Localization of rat glycine receptor α1 and α2 subunit transcripts in the developing auditory brainstem
Authors: Piechotta Kerstin , Weth Franco , Harvey Robert J. , Friauf Eckhard
Published: October 2004

Glycine receptors (GlyRs), aside from GABAA receptors, mediate fast postsynaptic inhibition in the mammalian nervous system. Spatial and temporal expression of the genes encoding ligand‐binding α subunits (α1–α4) and the structural β subunit leads to the formation of various GlyR isoforms. Currently, the idea of the GlyRs containing the “adult” α1 subunit replacing those with the “neonatal” α2 subunit during early postnatal development predominates. Here, we describe the patterns of expression of the GlyR α1 and α2 subunit genes in the rat auditory brainstem between postnatal day (P) 0 and P20, by using both nonradioactive and radioactive in situ hybridization. We show that the α1 subunit mRNA appears throughout the auditory brainstem during the first 8 postnatal days, which resembles the time of onset described within the spinal cord. In the rostral auditory nuclei (nuclei of the lateral lemniscus and inferior colliculus), the α1 subunit transcript appears later (P8) than in the caudal nuclei (cochlear nuclear complex and superior olivary complex; P0). Surprisingly, we found that low levels of the α2 subunit transcript are present in the auditory brainstem at birth and persist throughout the period analyzed. However, α2 subunit mRNA is present at high levels in other neonatal brainstem structures, such as cranial motor nuclei. Therefore, we conclude that the changes in GlyR composition in the auditory brainstem deviate from the classic α2 to α1 subunit switch observed in spinal cord. Our data suggest that genes for other GlyR subunits (e.g., α3 and α4) may be expressed during early development in the auditory brainstem. J. Comp. Neurol. 438:336–352, 2001. © 2001 Wiley‐Liss, Inc.
A Γ‐convergence result for the two‐gradient theory of phase transitions
Authors: Conti Sergio , Fonseca Irene , Leoni Giovanni
Published: October 2004

The generalization to gradient vector fields of the classical double‐well, singularly perturbed functionals,whereW(ξ) = 0 if and only if ξ =Aor ξ =B, andA−Bis a rank‐1 matrix, is considered. Under suitable constitutive and growth hypotheses onW, it is shown thatIεΓ‐converge towhereK*is the (constant) interfacial energy per unit area. © 2002 Wiley Periodicals, Inc.
Spectra of positive and negative energies in the linearized NLS problem
Authors: Cuccagna S. , Pelinovsky D. , Vougalter V.
Published: October 2004

We study the spectrum of the linearized NLS equation in three dimensions in association with the energy spectrum. We prove that unstable eigenvalues of the linearized NLS problem are related to negative eigenvalues of the energy spectrum, while neutrally stable eigenvalues may have both positive and negative energies. The nonsingular part of the neutrally stable essential spectrum is always related to the positive energy spectrum. We derive bounds on the number of unstable eigenvalues of the linearized NLS problem and study bifurcations of embedded eigenvalues of positive and negative energies. We develop the L2‐scattering theory for the linearized NLS operators and recover results of Grillakis [5] with a Fermi golden rule. © 2004 Wiley Periodicals, Inc.
Aspiration biopsy of nodular sarcoidosis of the muscle
Authors: Yamamoto Tetsuji , Nagira Keiko , Akisue Toshihiro , Marui Takashi , Hitora Toshiaki , Nakatani Tetsuya , Kurosaka Masahiro , Tsukamoto Ryuko
Published: October 2004

The nodular form of muscular sarcoidosis is rare and the condition is often confused with a soft tissue neoplasm. We present a case of nodular muscular sarcoidosis of the right calf in a 52‐yr‐old woman which was diagnosed by thin‐needle aspiration biopsy (TNAB). In this patient, a calf mass was the initial manifestation of sarcoidosis. Contrast‐enhanced computed tomographic scans of the calf showed a mass with peripheral ring‐like enhancement. T2‐weighted magnetic resonance images demonstrated a mass with central hypointensity and marked peripheral hyperintensity. TNAB revealed noncaseating epithelioid cell granulomas in association with multinucleated giant cells. Combined with the radiologic findings, TNAB is considered a useful modality for the diagnosis of nodular muscular sarcoidosis. Diagn. Cytopathol. 2002;26:109–112; DOI 10.1002/dc.10055 © 2002 Wiley‐Liss, Inc.
Fine‐needle aspiration biopsy of anaplastic large cell lymphoma, small cell variant with prominent plasmacytoid features: Case report
Authors: Gatter Ken M. , Rader Anne , Braziel Rita M.
Published: October 2004

Anaplastic large cell lymphoma (ALCL), according to the new WHO classification, is a diagnosis limited to T/NK cell lymphomas. We present a case that demonstrates a new morphologic variant of ALCL with significant possible pitfalls for the cytopathologist. A fine‐needle aspiration biopsy of a cervical lymph node showed a cellular aspiration comprised of medium‐sized plasmacytoid cells in a discohesive and focally loosely cohesive pattern. The cytologic diagnosis confirmed the presence of malignancy and noted the prominent plasmacytoid features. An accompanying comment favored melanoma and included a broad differential. No cell block was available for immunohistochemical stains. Immunophenotyping of the subsequent excisional node biopsy showed an anaplastic lymphoma kinase (ALK)‐positive ALCL. This case illustrates a new variant of ALCL. Although ALCL variants, such as small cell and lymphohistiocytic, are well recognized, the plasmacytoid features are an additional potential source for misdiagnosis. This case report shows that a cytopathologist should include ALK‐positive ALCL in the differential diagnosis of plasmacytoid proliferations cell because of the clinical importance of the ALK‐positive ALCL. Diagn. Cytopathol. 2002;26:113–116; DOI 10.1002/dc.10056 © 2002 Wiley‐Liss, Inc.
A design method of beam tilting antenna with multiple reactive loadings
Authors: Tanaka Takayuki , Sakitani Akihide , Egashira Shigeru , Aikawa Masayoshi
Published: October 2004

For the cellular systems used in portable telephones, down beam tilting is required from base station antennas. The authors have reported a design method of wire antennas with one or two loads for deriving the loading impedances to realize the tilt angle and directive gain provided as a condition. In the present paper, a method of design of a beam tilting antenna with more than three loads for better characteristics is discussed. In such a loaded wire antenna, determination of the locations for the loads and the antenna length is important. This paper proposes a method of determining the locations of the loads and the antenna length. In addition, by including a previously reported method of determining the loading impedance, a design method that achieves the desired tilt angle and high gain with suppressed sidelobes is presented. © 2002 Scripta Technica, Electron Comm Jpn Pt 1, 85(5): 1–10, 2002
Analysis of induced current density in grounded and ungrounded prolate spheroid models in concurrent ELF electric and magnetic fields
Authors: Matsumoto Takashi , Chiba Atsuo , Hayashi Noriyuki , Isaka Katsuo
Published: October 2004

Analyzed in this paper is the induced current density in the homogeneous prolate spheroid model of a biological object exposed to concurrent 60‐Hz vertical electrical field (1 kV/m), and horizontal and vertical magnetic fields (1 to 5 μT) with different phase angle. The analysis has been carried out separately considering the presence of electric and magnetic fields. The current density induced by the electric field is calculated using the finite element method, whereas the current density induced by the magnetic fields is calculated with exact solution for the prolate spheriod model. The total induced current density is the vector sum of the current density components induced by the electric and magnetic fields. It is found that the density of the total current is determined by the vertical electric field and horizontal magnetic field. The horizontal magnetic field has an important effect on the total induced current density distribution. The distribution of the density of the total current varies with the phase difference between the vertical electric and horizontal magnetic fields. As the model gets close to the ground, however, the contribution of the horizontal magnetic field to the total induced current density is found to decrease. © 2001 Scripta Technica, Electr Eng Jpn, 135(3): 8–15, 2001
Operating tests with a 6.6‐kV reduced model of rectifying‐type fault current limiter system
Authors: Ohkuma Takeshi , Sato Yoshibumi , Iwata Yoshihiro , Tokuda Noriaki , Matubara Yoshio , Asano Masakuni
Published: October 2004

Fault current limiters (FCL) are extensively needed to suppress fault currents, particularly for trunk power systems heavily connected to high‐voltage transmission lines, such as the 500‐kV‐class power system which constitutes the nucleus of the electric power system.

In this paper, we propose a new FCL system, consisting of solid‐state diodes, a dc coil, and a bypass ac coil, and describe the specifications of the trunk electric power system and the 6.6‐kV reduction model.

Also we propose a 6.6‐kV trial model and describe an efficiency test with a short circuit generator, which we have trial produced for the new FCL system. © 2001 Scripta Technica, Electr Eng Jpn, 137(3): 29–36, 2001
The effect of nozzle load resistance and stagnation gas pressure on the performance of a disk MHD generator with small area ratio
Authors: Masuda Junji , Torii Syunsuke , Tutsumi Masashi , Oda Noritaka , Okuno Yoshihiro , Yamasaki Hiroyuki
Published: October 2004

An experimental study on performance of a disk MHD generator was carried out using a shock‐tube driven facility. Effects of nozzle load resistance and stagnation gas pressure on the enthalpy extraction, the total pressure ratio, and the adiabatic efficiency were investigated for a disk MHD generator with a small area ratio. The enthalpy extraction and the adiabatic efficiency were found to be affected by the nozzle load resistance. The results suggest that the nozzle load resistance should be kept high for high performance of the disk MHD generator with small area ratio. Furthermore, an increase of stagnation pressure resulted in a slight increase of enthalpy extraction. However, the increase of stagnation pressure led to a remarkable increase of adiabatic efficiency. The increase of the adiabatic efficiency was due to an increase of the total pressure ratio. The effects of the electrical efficiency, the Mach number, and loss parameters for heat and friction on the total pressure ratio are discussed. The discussion suggests that the increase of total pressure ratio is due to a relative decrease of pressure loss due to wall friction. In addition, the highest adiabatic efficiency for cesium‐seeded argon was achieved in the present experiment without the introduction of inlet swirl. © 2001 Scripta Technica, Electr Eng Jpn, 137(3): 37–46, 2001
Borna disease virus‐induced accumulation of macrophage migration inhibitory factor in rat brain astrocytes is associated with inhibition of macrophage infiltration
Authors: Bacher Michael , Weihe Eberhard , Dietzschold Bernhard , Meinhardt Andreas , Vedder Helmut , Gemsa Diethard , Bette Michael
Published: October 2004

To test the hypothesis that macrophage migration inhibitory factor (MIF) plays a role in macrophage invasion during virus‐induced encephalitis, we analyzed the expression and cellular localization of MIF in the Borna disease virus (BDV)‐infected rat brain, monitored monocyte/macrophage infiltration, and evaluated the influence of anti‐inflammatory treatment with dexamethasone. MIF mRNA expression was restricted to neurons and remained unchanged after BDV infection or after dexamethasone treatment of either BDV‐infected or uninfected control rats. In contrast, MIF protein immunoreactivity (ir) was not only seen in neurons but also in glia. After BDV‐induced encephalitis and treatment of uninfected rats with dexamethasone, MIF ir was only slightly altered in neurons but moderately enhanced in tanycytes, ependyma, and choroid plexus epithelium and markedly increased or induced in astrocyte end‐feet at the blood‐brain barrier (BBB). The increase in MIF ir in astrocytes after BDV infection was blocked by dexamethasone. The induction or enhancement of MIF ir at the BBB significantly correlated with reduced numbers of infiltrating ED1‐positive monocytes/macrophages after BDV infection. Increased macrophage invasion was observed in regions where no astrocytic MIF was detected. The BDV‐ or dexamethasone‐induced accumulation of MIF protein in astrocytes in vivo in absence of detectable astrocytic MIF mRNA expression is most likely due to MIF translocation from neurons rather than to a constitutive or induced MIF mRNA expression in astrocytes. In conclusion, we provide evidence that translocation of MIF from neurons or other extracellular sources into astrocytes is likely to modulate the inflammatory process during the course of virus‐induced encephalitis by limiting monocyte/macrophage migration through the BBB. GLIA 37:291–306, 2002. © 2002 Wiley‐Liss, Inc.
Juxtavascular microglia migrate along brain microvessels following activation during early postnatal development
Authors: Grossmann Ruth , Stence Nick , Carr Jenny , Fuller Leah , Waite Marc , Dailey Michael E.
Published: October 2004

Some parenchymal microglia in mammalian brain tissues, termed “juxtavascular microglia,” directly contact the basal lamina of blood vessels; however, the functional consequences of this unique structural relationship are unknown. Here we used a rat brain slice model of traumatic brain injury to investigate the dynamic behavior of juxtavascular microglia following activation. Juxtavascular microglia were identified by confocal 3D reconstruction in tissue slices stained with a fluorescent lectin (FITC‐IB4) that labels both microglia and blood vessel endothelial cells. Immunolabeling confirmed that juxtavascular cells were true parenchymal microglia (OX42+, ED2−) and not perivascular cells or pericytes. Time‐lapse imaging in live tissue slices revealed that activating juxtavascular microglia withdraw most extant branches but often maintain contact with blood vessels, usually moving to the surface of a vessel within 1–4 h. Subsequently, some microglia migrate along the parenchymal surface of vessels, moving at rates up to 40 μm/h. Activated juxtavascular microglia sometimes repeatedly extend veil‐like protrusions into the surrounding tissue, consistent with a role in tissue surveillance. Juxtavascular cells were twice as likely as nonjuxtavascular cells to be locomotory by 10 h in vitro, suggesting an enhanced activation response. Moreover, 38% of all juxtavascular cells migrated along a vessel, whereas this was never observed for a nonjuxtavascular cell. These observations identify a mobile subpopulation (10%–30%) of parenchymal microglia that activate rapidly and are preferentially recruited to the surfaces of blood vessels following brain tissue injury. The dynamic and sustained interaction of microglia with brain microvessels may facilitate signaling between injured brain parenchyma and components of the blood‐brain barrier or circulating immune cells of the blood in vivo. GLIA 37:229–240, 2002. © 2002 Wiley‐Liss, Inc.
Preparation of a monoclonal antibody to citrullinated epitopes: Its characterization and some applications to immunohistochemistry in human brain
Authors: Nicholas Anthony P. , Whitaker John N.
Published: October 2004

Using hybridoma technology, an IgM monoclonal antibody (mAb), designated as F95, was developed against a deca‐citrullinated peptide (DCP) consisting of 10 citrulline residues and a carboxyl Gly‐Gly‐Cys through which DCP was covalently linked to an activated carrier protein, keyhole limpet hemocyanin (KLH). Clones were selected on the basis of not reacting with human unmodified and noncitrullinated myelin basic protein (MBP), MBP‐C1, but reacting well with human citrullinated MBP (MBP‐C8). When tested by ELISA, this mAb demonstrated minimal reactivity with human MBP‐C1, varying reactivity with the C2–C5 isomers of human MBP, moderate binding with guinea pig MBP‐C8, and strong reactivity with human MBP‐C8. By ELISA, mAb F95 was directed predominantly against citrulline, not MBP, as revealed by its binding to DCP linked with activated KLH, bovine serum albumin (BSA), or ovalbumin (OA), but not with KLH, BSA, or OA alone. Immunohistochemistry of normal human brain demonstrated that F95 stained central nervous system myelin and a subset of astrocytes. Given the citrulline‐directed features of mAb F95, this immunohistochemical pattern suggests that certain astroglial filaments expressing glial fibrillary acidic protein also contain citrulline‐bearing components. These potentially implicate citrullinated proteins, notably in astroglial filaments, in a variety of normal and pathological neurobiological processes. GLIA 37:328–336, 2002. © 2002 Wiley‐Liss, Inc.
Anatomically informed basis functions in multisubject studies
Authors: Kiebel Stefan , Friston Karl J.
Published: October 2004

We describe the use of anatomically informed basis functions (AIBF) in the analysis of multisubject functional imaging studies. AIBF are used to specify an anatomically informed spatial model that embodies anatomical knowledge for the statistical analysis of neuroimaging data. In a previous communication, we showed how AIBF can be used to incorporate prior anatomical constraints in single subject functional magnetic resonance image (fMRI) analyses to augment their anatomical precision. In this paper, we extend AIBF such that it can be applied to multisubject studies using fMRI or PET. The key concept is that, after spatial normalization, a canonical cortical surface can be used to generate a forward model of signal sources for all subjects. By estimating the hemodynamic signal in this canonical AIBF‐space and then projecting it back into the voxel‐space, one effectively extracts functional activity that is smooth, within and only within, the cortical sheet while attenuating other components unrelated to the physiological process of interest. The ensuing procedure can be considered as a highly non‐stationary, anisotropic anatomically informed [de]convolution or smoothing. It is shown that this procedure offers various advantages compared to existing conventional methods for the analysis of multisubject studies, in particular it is more sensitive to underlying activations. Hum. Brain Mapping 16:36–46, 2002. © 2002 Wiley‐Liss, Inc.
Simultaneous measurements of cerebral oxygenation changes during brain activation by near‐infrared spectroscopy and functional magnetic resonance imaging in healthy young and elderly subjects
Authors: Mehagnoul‐Schipper D. Jannet , van der Kallen Bas F.W. , Colier Willy N.J.M. , van der Sluijs Marco C. , van Erning Leon J.Th.O. , Thijssen Henk O.M. , Oeseburg Berend , Hoefnagels Willibrord H.L. , Jansen René W.M.M.
Published: October 2004

Near infrared spectroscopy (NIRS) and functional magnetic resonance imaging (fMRI) both allow non‐invasive monitoring of cerebral cortical oxygenation responses to various stimuli. To compare these methods in elderly subjects and to determine the effect of age on cortical oxygenation responses, we determined motor‐task‐related changes in deoxyhemoglobin concentration ([HHb]) over the left motor cortex in six healthy young subjects (age 35 ± 9 years, mean ± SD) and five healthy elderly subjects (age 73 ± 3 years) by NIRS and blood‐oxygen‐level‐dependent (BOLD) fMRI simultaneously. The motor‐task consisted of seven cycles of 20‐sec periods of contralateral finger‐tapping at a rate as fast as possible alternated with 40‐sec periods of rest. Time‐locked averages over the seven cycles were used for further analysis. Task‐related decreases in [HHb] over the motor cortex were measured by NIRS, with maximum changes of −0.83 ± 0.38 μmol/L (P < 0.01) for the young and −0.32 ± 0.17 μmol/L (P < 0.05) for the elderly subjects. The BOLD‐fMRI signal increased over the cortex volume under investigation with NIRS, with maximum changes of 2.11 ± 0.72% (P < 0.01) for the young and 1.75 ± 0.71% (P < 0.01) for the elderly subjects. NIRS and BOLD‐fMRI measurements showed good correlation in the young (r = −0.70, r2 = 0.48, P < 0.001) and elderly subjects (r = −0.82, r2 = 0.67, P < 0.001). Additionally, NIRS measurements demonstrated age‐dependent decreases in task‐related cerebral oxygenation responses (P < 0.05), whereas fMRI measurements demonstrated smaller areas of cortical activation in the elderly subjects (P < 0.05). These findings demonstrate that NIRS and fMRI similarly assess cortical oxygenation changes in young subjects and also in elderly subjects. In addition, cortical oxygenation responses to brain activation alter with aging. Hum. Brain Mapping 16:14–23, 2002. © 2002 Wiley‐Liss, Inc.
Prediction of survival in patients with head and neck cancer using the histoculture drug response assay
Authors: Singh Bhuvanesh , Li Rongou , Xu Li , Poluri Ashok , Patel Snehal , Shaha Ashok R. , Pfister David , Sherman Eric , Goberdhan Andy , Hoffman Robert M. , Shah Jatin
Published: October 2004

Background

Chemoresponse is a significant outcome predictor in patients with head and neck cancer, regardless of the treatment modality used. The histoculture drug response assay (HDRA) has been shown to be a reliable method for in vitro chemoresponse assessment. In this study, we have correlated the HDRA assessment with survival in patients with head and neck squamous cell carcinoma (HNSCC).

Method

Tumor specimens from 41 of 42 patients undergoing treatment for HNSCC were successfully evaluated by the HDRA. Tumor tissue was histocultured on Gelfoam sponges gel in 24‐well plates, followed by treatment with cisplatin (15 μg/mL) or 5‐fluorouracil (40 μg/mL) in triplicate. A control group received no drug treatment. After completion of drug treatment, the relative cell survival in the tumors was determined using the MTT assay. The inhibition rate (IR) for each drug was calculated relative to the control for each case, and sensitivity was defined as a tumor IR of greater than 30%. Treatment was based on established protocols for the location and stage of the tumor and included surgery, radiation, and/or chemotherapy. Survival comparisons were performed using the generalized Wilcoxon test for the comparison of Kaplan‐Meier survival curves.

Results

Resistance to 5‐fluorouracil was present in 13 cases (32%), to cisplatinum in 13 cases (32%), and to both agents in 11 cases (27%). The 2‐year cause‐specific survival was significantly greater for patients sensitive to 5‐fluorouracil (85% vs 64%; p = .04), cisplatinum (86% vs 64%; p = .05), or both agents (85% vs 63%; p = .01). The association between HDRA assessment of chemoresponse and clinical outcome remained significant even after controlling for the effects of TNM stage and the presence of recurrent cancer at presentation by multivariate analysis.

Conclusions

Chemosensitivity determined by the HDRA seems to be a strong predictor of survival in patients with advanced HNSCC and should be considered further. © 2002 Wiley Periodicals, Inc.
Role of planned neck dissection for advanced metastatic disease in tongue base or tonsil squamous cell carcinoma treated with radiotherapy
Authors: Roy Saswata , Tibesar Robert J. , Daly Kathleen , Pambucian Stephan , Lee H. K. , Gapany Markus , Adams George L.
Published: October 2004

Objective

At the conclusion of this article, the reader should be able to discuss the need for planned neck dissection for advanced cervical diseases in the tongue base and tonsil cancer after treatment with radiotherapy.

Background

In the past 5 years, we have treated patients with squamous cell carcinoma of the tonsil and tongue base with radiotherapy as the primary therapeutic modality. A planned complete neck dissection was performed on all patients with N2 or greater cervical disease regardless of response to radiotherapy. Composite resection was performed when there was persistent disease at the primary site. Although the “radiation‐first” therapeutic approach for tongue base and tonsil cancer is widely accepted, the planned neck dissection for neck metastases remans controversial. The objective of the study was to determine the validity of planned neck dissection after radiotherapy for N2 disease.

Methods

Medical records of patients with primary squamous cell carcinoma of the tongue base and tonsil with neck metastasis staged N2 or greater were reviewed. Between 1994 and 1999, 36 such patients were treated with curative radiation therapy. Response was assessed 6 to 8 weeks after completion of treatment with clinical examination and CT imaging. All patients underwent planned neck dissection. We reviewed the clinical and radiographic response of neck disease to radiotherapy as it correlated with the histopathologic findings.

Results

Of the 36 patients, 17 had clinical and CT evidence of persistent disease. In this group, 65% had pathologically confirmed diseases at surgery. Of the 9 patients with no evidence of disease on clinical examination, negative biopsy at the primary site, and a negative CT scan, 33% (three of nine) still had residual disease in the neck dissection specimen.

Conclusions

Positive findings on clinical examination and CT can predict the presence of malignancy after radiation therapy. However, a negative CT and clinical examination are limited in predicting a complete response. These data lend support to the role of planned neck dissection after radiotherapy of N2 neck disease. © 2002 Wiley Periodicals, Inc.
Histopathologic reaction of a calcium phosphate cement for alveolar ridge augmentation
Authors: Sugawara Akiyoshi , Fujikawa Kenji , Kusama Kaoru , Nishiyama Minoru , Murai Seidai , Takagi Shozo , Chow Laurence C.
Published: October 2004

The objective of the present study was to evaluate the feasibility of using a calcium phosphate cement (CPC) in the reconstruction of a defective alveolar ridge in conjunction with implant placement. The CPC consisted of an equimolar amount of tetracalcium phosphate and dicalcium phosphate anhydrous. At the beginning of the experiment, all mandibular premolar teeth of mature beagle dogs were extracted. After 1 month of healing, alveolar bone was reduced to make a space for a CPC block that was prefabricated from a CPC mixed with water at a powder/liquid ratio of 5 g/mL. After an additional month, 8‐mm long hydroxyapatite‐coated titanium implants were placed in such a way that the apical half was embedded into alveolar bone and the coronal half in the preformed CPC block. The dogs were sacrificed and biopsies were obtained at 1, 3, and 6 months after surgery. Sections that included implants were evaluated for integration of the CPC block to the alveolar bone and of the implant to the alveolar bone. Additional sections without the implants served as controls. The results obtained from this study show that the CPC ridge augmentation gradually is replaced by natural bone. Six months after surgery, histopathologic features of the augmentation area were quite similar to those of natural alveolar bone. The coronal half of the implants, previously surrounded by the CPC block, was firmly fixed by natural bone. Therefore, this method may be useful for increasing the height of the alveolar ridge. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 47–52, 2002
Synthesis of macroporous hydroxyapatite scaffolds for bone tissue engineering
Authors: Li Shi Hong , De Wijn Joost R. , Layrolle Pierre , De Groot Klaas
Published: October 2004

A novel method of preparing macroporous hydroxyapatite (HA) by dual‐phase mixing was developed: HA slurry and Polymethylmethacrylate (PMMA) resin were mixed together at the volume ratio of 1:1. After pyrolytic removal of the PMMA phase, HA with an open porous structure was obtained. In this way, the porosity of the ceramic was limited to 50%. Attempts to increase the porosity by adding more PMMA resin were confronted with the technical hurdle of sample collapse during the pyrolysis process. To increase the porosity and to improve pore interconnection, an extra foaming step was introduced before the polymerization of PMMA resin. Three foaming agent systems were tried, based on the reactions of citric acid and (bi)carbonate salts: sodium bicarbonate, calcium carbonate, and ammonium bicarbonate. Although all the three foaming agents were able to increase the porosity up to 70%, keeping all the pores interconnected throughout, only ammonium bicarbonate system turned out to be applicable to make HA scaffolds or implants, because both NaHCO3 and CaCO3 systems caused alkalic residues in the final ceramic. The porous HA samples were fully characterized by FTIR, XRD, ESEM (EDX), and optical microscopy. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 109–120, 2002
Liquid photocurable biodegradable copolymers: In vivo degradation of photocured poly(ϵ‐caprolactone‐co‐trimethylene carbonate)
Authors: Mizutani Manabu , Matsuda Takehisa
Published: October 2004

Liquid photoreactive poly(ϵ‐caprolactone‐co‐trimethylene carbonate)s endcapped with a coumarin group [coumarinated poly(CL/TMC)s] were prepared using tetra‐functional hydroxylated substances such as pentaerythritol or four‐branched poly(ethylene glycol), b‐PEG. These coumarinated copolymers are tetra‐branched and exist as a viscous liquid (MW 5 ×103∼7 × 103). They were photocured by ultraviolet (UV) light irradiation to obtain a swelling or nonswelling solid under water, depending on the type of initiator used. The resultant films were implanted into the subcutaneous tissues of rats for up to 5 months. The photocured b‐PEG‐based copolymer was completely degraded and sorbed within a 1 month. On the other hand, surface‐eroding degradation of pentaerythritol‐based, coumarinated poly(CL/TMC) progressed with implantation time, and minimal recruitment of neutrophils, macrophages, and multinucleated giant cells was observed over the implantation period. Among the pentaerythritol‐based copolymers, the fastest surface erosion was observed for the copolymer with the highest ϵ‐caprolactone content. Microfabricated films with microarrays in which photoconstructs were stereolithographically prepared, using three different coumarinated copolymers at different regions, showed that upon implantation there was regionally differentiated biodegradation of microarrays, and the degree of region‐specific biodegradation depended on the type of photocured copolymer. The observed tendency for biodegradation was in good agreement with that observed during implantation of individual films in vivo. This study also demonstrates that the use of multi‐material‐arrayed films enables the determination of different responses in vivo using only one sample. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 53–60, 2002
Soft‐tissue response to silicone and poly‐L‐lactic acid implants with a periodic or random surface micropattern
Authors: Parker J. A. T. C. , Walboomers X. F. , Von den Hoff J. W. , Maltha J. C. , Jansen J. A.
Published: October 2004

Tissue reaction to biomaterials is dependent on properties such as surface topography. The aim of this study was to evaluate the tissue reaction around implants with different surface topographies. We made coin‐shaped silicone and poly‐L‐lactic acid (PLLA) implants with double‐sided parallel microgrooves (depth 1.0 μm; width 10.0 μm) and random roughness on a micrometer scale. The control implants were smooth. These implants were inserted into subcutaneous pockets created on the flanks of goats. After 1, 3, or 12 weeks, the goats were sacrificed and the implants retrieved and histologically processed. Light microscopic evaluation revealed the formation of fibrous tissue capsules around all implant materials. The PLLA did not visibly degrade during the study period. Histomorphometric analyses were performed on capsule thickness, capsule quality, and on the implant–tissue interface quality. Compared with the silicone implants, the capsules around the PLLA implants showed significantly better capsule quality. Compared to the smooth implants, the capsules around the microgrooved implants were thicker, but the capsules around the roughened implants were thinner. However, randomly roughened implant surfaces generally elicited a stronger and more prolonged inflammatory reaction compared to smooth and microgrooved implant surfaces. We conclude that the application of microgrooves or random surface roughness to polymer implants apparently does not have beneficial effects on peri‐implant tissue healing. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 91–98, 2002
Calcium oscillations in Xenopus egg cycling extracts
Authors: Tokmakov Alexander A. , Sato Ken‐Ichi , Fukami Yasuo
Published: October 2004

Cell cycle in various types of cells and in early embryos is often accompanied by transient changes in the concentration of free cytosolic calcium. In the present study, using fluorescent indicator fura‐2, we demonstrate that Ca2+ oscillates cyclically with an amplitude of about 100 nM and a period of mitotic cycle in cell‐free Xenopus egg cycling extracts. It peaks in early metaphase just preceding mitotic reactivation of Cdc2 kinase and MAPK and reaches a minimum in interphase. The source of Ca2+ in the extracts is a particulate fraction containing egg intracellular Ca2+ stores, since the addition of a calcium‐mobilizing second messenger, inositol 1,4,5‐trisphosphate (IP3), induced a transient increase in Ca2+. The inclusion of heparin, an IP3 receptor antagonist, or ultrafiltration of the extracts prevented Ca2+‐releasing activity of IP3. The depletion of Ca2+ in the extracts by the calcium chelator BAPTA resulted in the blockade of cell cycle at different stages, depending on the time of drug administration. The addition of BAPTA late in interphase blocked cell cycle at mitotic entry in prophase, whereas its application in anaphase or telophase blocked the extracts in early interphase. BAPTA administration in metaphase before transition to anaphase brought about a metaphase‐like arrest in the cycling extracts. Inhibition of IP3‐induced calcium release by heparin also arrested cell cycle progression in the cycling extracts. J. Cell. Biochem. 82: 89–97, 2001. © 2001 Wiley‐Liss, Inc.
c‐Myc localization within the nucleus: Evidence for association with the PML nuclear body
Authors: Smith Kelly P. , Byron Meg , O'Connell Brenda C. , Tam Rose , Schorl Christoph , Guney Isil , Hall Lisa L. , Agrawal Pooja , Sedivy John M. , Lawrence Jeanne B.
Published: October 2004

Definitive localization of c‐Myc within the nucleus is important to fully understand the regulation and function of this oncoprotein. Studies of c‐Myc distribution, however, have produced conflicting results. To overcome technical challenges inherent in c‐Myc cytology, we use here three methods to visualize c‐Myc and in addition examine the impact of proteasome inhibition. EYFP or HA‐tagged Myc was reintroduced by stable transfection intomycnull diploid rat fibroblasts, replacing endogenous Myc with tagged Myc expressed at or near normal levels. This tagged Myc is shown to functionally replace the endogenous Myc by restoration of normal cell morphology and growth rate. We were able to confirm key findings using antibodies to the endogenous c‐Myc and/or its partner, Max. Contrary to some published reports, by all three methods the c‐Myc protein in rat fibroblasts distributes predominantly throughout the nucleus in a dispersed granular pattern, avoiding the nucleolus. Importantly, however, several findings provide evidence for an unanticipated relationship between c‐Myc and PML nuclear bodies, which is enhanced under conditions of proteasome inhibition. Evidence of Max concentration within PML bodies is shown both with and without proteasome inhibition, strengthening the relationship between PML bodies and Myc/Max. Some accumulation of Myc and Max in nucleoli upon proteasome inhibition is also observed, although co‐localization of ubiquitin was only seen with PML bodies. This work provides a comprehensive study of c‐Myc distribution and also presents the first evidence of a relationship between turnover of this oncoprotein and PML nuclear bodies, known to break down in certain cancers. © 2004 Wiley‐Liss, Inc.
Electron transfer in bis(hydrazines), a critical test for application of the Marcus model
Authors: Blomgren Fredrik , Larsson Sven , Nelsen Stephen F.
Published: October 2004

Electron transfer in the cations of bis(hydrazines), bridged by six different π‐systems (compounds 1–6) is studied using ab initio and density functional theory (DFT) methods. Due to ionization from an antibonding combination of the lone‐pair orbitals of the nitrogens in one of the hydrazine units, conjugation is introduced in the NN bond of that unit. This leads to a shortening of the NN bond distance and an increase of the planarity around the nitrogens. Due to steric hindrance, this causes an increase of the angle, called φ, between the lone‐pair orbital on the nitrogen attached to the bridge and the p‐orbital on the adjacent bridge carbon for the ionized unit in the charge localized, relaxed state of the molecule. This angle controls the magnitude of the electronic coupling. In the fully delocalized symmetric transition state of the ion, however, this angle is low for both units, due to the fact that the conjugation introduced at the ionized hydrazine unit is now shared between both units. An extended π‐system is formed including the orbitals of the hydrazine units and the bridge, which leads to a large electronic coupling. The electronic coupling derived by optical methods, corresponding to the structure of the relaxed, asymmetric cation with a large φ for the ionized unit, appears to be much smaller. We believe this is due to an approximate cosine dependence on φ of the coupling. The calculations carried out support these conclusions. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 655–664, 2001
Software news and updates
Authors: Dijkstra Fokke , van Lenthe Joop H.
Published: October 2004

A parallel version of the valence bond program TURTLE has been developed. In this version the calculation of matrix elements is distributed over the processors. The implementation has been done using the message‐passing interface (MPI), and is, therefore, portable. The parallel version of the program is shown to be quite efficient with a speed‐up of 55 at 64 processors. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 665–672, 2001
Benzdiynes revisited: ab initio and density functional theory
Authors: Arulmozhiraja Sundaram , Sato Tadatake , Yabe Akira
Published: October 2004

Ab initio and density functional theory (DFT) studies were performed on three isomers of tetradehydrobenzene (benzdiynes). Four different density functionals (BPW91, BLYP, B3LYP, and B1LYP) and two higher levels of theory [QCISD and CCSD(T)] incorporating basis sets up to Dunning's correlation‐consistent polarized valence triple‐ζ (cc‐pVTZ) were utilized for this purpose. Stability tests showed that more stable solutions were available for 1,4‐benzdiyne with unrestricted than with restricted DFT, while solutions obtained with later descriptions of 1,3‐benzdiyne and 1,2,3,5‐tetradehydrobenzene were stable. UB3LYP provided better geometry for 1,4‐benzdiyne. Unlike in an earlier study, the energy difference between 1,2,3,5‐tetradehydrobenzene and 1,4‐benzdiyne calculated with the B3LYP functional coincided well with that calculated at CCSD(T): 13.07 and 14.32 kcal/mol at the B3LYP/cc‐pVTZ and CCSD(T)/cc‐pVTZ levels, respectively. 1,2,3,5‐Tetradehydrobenzene was 8 kcal/mol more stable than 1,3‐benzdiyne at the CCSD(T)/cc‐pVTZ level. The heats of formation of benzdiynes were obtained by using the G2, CBS‐Q, and CBS‐QB3 methodologies. The heats of formation calculated for 1,3‐benzdiyne and 1,2,3,5‐tetradehydrobenzene were 208.6 and 197.9 kcal/mol, respectively, at the CBS‐QB3 level of theory. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 923–930, 2001
A theoretical study of solvent effect and reaction mechanism of electron transfer reaction between indole side chain and phenol side chain of peptide involving tryptophan and tyrosine
Authors: Li Xiang‐Yuan , Liu Ji‐Feng
Published: October 2004

The mechanisms for the electron transfer between the indole side chain and phenol side chain of peptides involving tryptophan and tyrosine have been studied by ab initio calculation in this work. The solvent effect has been considered by using the conductor‐like screening model (COSMO). Three mechanisms including the two‐proton elimination mechanism, the hole transfer without proton deprotonation, and the step‐by‐step mechanism for the electron transfer processes between indole and phenol have been discussed. From the theoretical calculations, we can conclude that, for the electron transfer between indole and phenol, and consequently between tryptophan and tyrosine, a deprotonation process is necessary, otherwise the ET process is difficult to proceed. There are two deprotonation cases that make the successive electron transfer feasible: one is that both the proton attached to indole N and that attached to phenol O, are removed before the ET process, the other is that the proton attached to indole N is first removed, then the proton attached to O of phenol group transfers to the indole group, and the ET follows. The comparison between our theoretical predication and the experimental conclusion has been made. The influence of the donor‐acceptor distance on the ET rate constant for the intramolecular electron transfer has been investigated in solution. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1067–1081, 2001
IMiCMO: a new integrated ab initio multicenter molecular orbitals method for molecular dynamics calculations in solvent cluster systems
Authors: Morita Shoji , Sakai Shogo
Published: October 2004

A new computational scheme integrating ab initio multicenter molecular orbitals for determining forces of individual atoms in large cluster systems is presented. This method can be used to treat systems of many molecules, such as solvents by quantum mechanics. The geometry parameters obtained for three models of water clusters by the present method are compared with those obtained by the full ab initio MO method. The results agree very well. The scheme proposed in this article also intended for use in modeling cluster systems using parallel algorithms. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1107–1112, 2001