bluuebunny/crossref_metadata_2025 huggingface dataset:
Presentation, treatment, and outcome of oral cavity cancer: A national cancer data base report
Authors: Funk Gerry F. , Karnell Lucy Hynds , Robinson Robert A. , Zhen Weining K. , Trask Douglas K. , Hoffman Henry T.
Published: October 2004

Background

Oral cancer has been identified as a significant public health threat. Systematic evaluation of the impact of this disease on the US population is of great importance to health care providers and policy makers.

Methods

This study used the National Cancer Data Base (NCDB) to evaluate associations between demographic and disease characteristics, treatment, and survival for patients with oral cavity cancer in the United States. Of patients diagnosed between 1985 and 1996, 58,976 were extracted from the NCDB. ANOVAs were performed on selected cross‐tabulations, and relative survival was used to calculate outcome.

Results

Median age of patients was 64.0 years. Men made up 60.2% of patients. Pathologic diagnosis was squamous cell carcinoma (SCC) in 86.3% of cases. Younger patients had a much higher frequency of non‐SCC, and this was related to survival in these patients. African‐Americans (independent of income), lower income patients, and patients with higher grade disease were seen more frequently with advanced‐stage SCC. Five‐year relative survival for SCC cases was lower for older patients, men, and African‐Americans.

Conclusions

This study addressed many issues related to oral cancer that have been previously discussed in the literature. The demographic, site, stage, histologic, and survival data available for this large number of cases in the NCDB allowed an accurate characterization of the contemporary status of oral cancer in the United States. © 2002 John Wiley & Sons, Inc.
Melan‐A as a useful diagnostic immunohistochemical stain for the diagnosis of primary sinonasal melanomas
Authors: Snyder Matthew L. , Paulino Augusto F. G.
Published: October 2004

Background

Sinonasal melanomas are rare neoplasms whose diagnosis may require confirmatory immunohistochemical stains. S‐100 protein and HMB‐45, the stains most commonly used, have varying sensitivities and specificities. Melan‐A, a more recent melanoma‐specific marker, may prove helpful when S‐100 protein and HMB‐45 stains are negative or equivocal.

Methods

Seven cases of sinonasal melanoma were assessed for reactivity with Melan‐A, S‐100 protein and HMB‐45.

Results

The study group consisted of two women and five men ages 40 to 83. Six of the neoplasms were strongly positive for S‐100 protein. One case was negative for S‐100 protein and HMB‐45 but positive for Melan‐A. HMB‐45 staining varied between diffusely positive (three cases), focally positive (two cases), and negative (two cases). All cases were positive for Melan‐A either diffusely (four cases) or focally (three cases).

Conclusion

Because Melan‐A can be positive in cases that are S‐100 protein or HMB‐45 negative, it is a useful component in the immunohistochemical panel for the diagnosis of sinonasal melanomas. © 2002 John Wiley & Sons, Inc. Head Neck 24: 52–55, 2002.
Endoglin (CD105) expression in squamous cell carcinoma of the oral cavity
Authors: Schimming Ronald , Marmé Dieter
Published: October 2004

Background

Increasing evidence suggests that endoglin (CD105) is a new powerful marker of neovascularization in solid malignancies. To explain the rating of CD105 expression in 51 squamous cell carcinoma of the oral cavity (SCCOC) we analyzed CD105 expression in tumor tissue and adjacent normal healthy mucosa.

Methods

Mean CD105 density was quantitated by counting the number of CD105‐immunostained blood vessels. The results were compared with clinical parameters like T and N stage, grading, tumor localization, and specific characteristics of patients by means of statistical analysis.

Results

Endoglin expression in tumor tissue was significantly higher than in normal healthy mucosa (p < .001). With the exception of T3 (n = 2), a higher T stage was correlated with higher endoglin expression. No statistical correlation was found in the analysis of patient's age, gender, and tumor localization.

Conclusions

Endoglin expression is up‐regulated in SCCOC compared with normal healthy oral mucosa. Endoglin may have a significant role in the development of SCCOC and might be relatively more specific than commonly used endothelial markers. © 2002 John Wiley & Sons, Inc.
Frozen section during parotid surgery revisited: Efficacy of its applications and changing trend of indications
Authors: Wong David Sau Yan
Published: October 2004

Background

Efficacy of frozen sections was assessed in terms of its various applications. The changing role of frozen sections in parotid surgery was examined.

Method

Records of parotid operations over a 15‐year period in a University Department of Head & Neck Surgery were reviewed.

Results

Of 241 operations, frozen sections were performed on 32. Applications of frozen sections included diagnosis, margin clearance, and checking suspicious lymph nodes and nerve invasion. The false‐positive rate for malignancy was 12.5%. Margins may still be involved despite correct tissue diagnosis from sampling error. No inappropriate surgery resulted from the information obtained. With the advent of fine‐needle aspiration, frozen sections were less often called for and a shift from a diagnostic role to margin checking was seen. Frozen sections picked up all unsuspected malignant tumors.

Conclusion

Frozen sections are helpful when interpreted cautiously, but clinical assessment and fine‐needle aspiration are also important components in the workup. © 2002 John Wiley & Sons, Inc.
Squamous cell carcinoma arising in the skin of a deltopectoral flap 27 years after pharyngeal reconstruction
Authors: Iseli Tim A. , Hall Francis T. , Buchanan Malcolm R. , Kleid Stephen M.
Published: October 2004

Background

Development of a second primary squamous cell carcinoma in the skin of a flap used for pharyngeal reconstruction is rare.

Methods

A case of squamous cell carcinoma is presented arising in a deltopectoral flap used to reconstruct the hypopharynx 27 years after total laryngectomy. Three previous reports found on review of the literature are summarized.

Results

A second primary squamous cell carcinoma may arise in the skin of a myocutaneous flap in the absence of any obvious risk factors.

Conclusion

We suspect that long‐term exposure of the skin of the flap lining the pharynx to saliva may have been a significant factor in the development of this malignancy. Long‐term follow up and awareness of this complication is required for patients with soft tissue reconstruction of the oral cavity and pharynx. © 2002 John Wiley & Sons, Inc. Head Neck 24: 87–90, 2002.
Malignant melanoma in the palate of a 3‐month‐old child
Authors: Owens Jonathan M. , Gomez Jose A. , Byers Robert M.
Published: October 2004

Background

Malignant mucosal melanoma of the head and neck is a rare cancer in adults that carries a grave prognosis. Three mucosal melanomas in pediatric patients have previously been reported.

Methods

We present here the youngest case of malignant mucosal melanoma of the head and neck in a 3‐month‐old boy. He presented with a 2 × 2‐mm‐pigmented lesion on the anterior maxillary alveolus. The patient was treated with local excision alone.

Results

The patient has remained disease free with regular follow‐up for 117 months.

Conclusion

Based upon this case and the few cases reported in the literature, mucosal melanoma is a much less common disease in children than in adults. Further, juvenile mucosal melanoma displays a benign clinical behavior. © 2002 John Wiley & Sons, Inc. Head Neck 24: 91–94, 2002.
Altered mossy fiber distributions in adult Fmr1 (FVB) knockout mice
Authors: Ivanco Tammy L. , Greenough William T.
Published: October 2004

The fragile‐X mental retardation protein (FMRP) is greatly reduced or absent in individuals with fragile‐X mental retardation syndrome, a common, heritable form of mental retardation. Morphological studies suggest that this protein functions in normal synapse maturation and neuronal plasticity. Examination of human brain autopsy tissue has shown that fragile‐X patients exhibit long, thin spines more frequently, and stubby mushroom‐shaped spines less frequently, than these two types of spines are seen in normal autopsy tissue. Fragile‐X tissue also has a greater density of these spines along dendrites, which suggests a possible failure of synapse elimination. Fmr1 knockout mice and wild‐type littermates brains were processed for Timm staining, which reveals the zinc‐rich terminals of the dentate gyrus, the mossy fibers. The Fmr1 knockout mice exhibited a pattern of Timm granule‐staining within the stratum oriens of subfield CA3 and the inner molecular layer that was significantly different than staining seen in wild‐type animals. The sources and consequences of the altered terminal staining are unclear, but are discussed in relation to immature synapse morphology, a failure of normal regression of synapses, and a potential biological penalty of such a failure to regress. Hippocampus 2002;12:47–54. © 2002 Wiley‐Liss, Inc.
Behavioral and neuroanatomical characterization of the Fmr1 knockout mouse
Authors: Mineur Yann S. , Sluyter Frans , de Wit Sanne , Oostra Ben A. , Crusio Wim E.
Published: October 2004

Previous studies showed the Fmr1 knockout (KO) mouse to be an excellent animal model for human fragile‐X syndrome. The aim of this study was to further characterize the phenotype of these animals. Neuroanatomically, KO male mice were compared to wild‐types (littermates) with respect to their sizes of hippocampal intra‐ and infrapyramidal mossy fiber (IIPMF) terminal fields. Behaviorally, they were tested in four different paradigms, each measuring different aspects of cognitive and emotional behavior: elevated plus maze (anxiety), neutral cage (aggression), open field (exploration), and radial maze (spatial memory). The results showed a diminished ability for radial maze learning associated with smaller sizes of IIPMF terminal fields. In addition, Fmr1 knockout animals exhibited increased locomotor activity, while no differences were found for aggression and anxiety. These data suggest the involvement of FMRP protein in the development of spatial learning and the sprouting of IIPMF terminal fields. Hippocampus 2002;12:39–46. © 2002 Wiley‐Liss, Inc.
Genetic approach to variability of memory systems: Analysis of place vs. response learning and Fos‐related expression in hippocampal and striatal areas of C57BL/6 and DBA/2 mice
Authors: Passino Enrica , Middei Silvia , Restivo Leonardo , Bertaina‐Anglade Valérie , Ammassari‐Teule Martine
Published: October 2004

C57 and DBA mice were trained in a crossed maze to assess possible strain differences in place or response learning as a function of training duration ( 8 or 17 days) and extramaze cueing conditions. The first condition consisted of a diffuse visually cued environment (rich cueing). The second was the same plus an explicit visual cue marking the direction of the baited arm (rich cueing plus cue). The third was a featureless environment (poor cueing). During training, mice were released from the south arm and rewarded in the east arm. Probe trials on which mice were released from the north arm and allowed to choose either the east (place learning) or the west (response learning) arm were given either on the ninth (PT1) or the eighteenth (PT2) days. Strain × context differences in the activation of the dorsal hippocampus and the dorsolateral striatum were examined by analyzing Fos expression following each probe trial. Results first showed that C57 were essentially place‐learners, whereas no learning modality was predominant in DBA, except on the PT2 run with the explicit cue available. Examination of Fos expression in C57 trained under “rich cueing” and “rich cueing plus cue” conditions revealed a strong and parallel increase of immunoreactivity in the hippocampus and dorsolateral striatum following PT1 that decreased under PT2. In that strain, the similar time‐course variation of Fos expression in both areas suggests a simultaneous involvement of hippocampal‐ and striatal‐based learning mechanisms, even if those controlled by the hippocampus were prevailing on those controlled by the dorsolateral striatum. In DBA mice, however, the absence of any preferential learning modality was associated with 1) a consistent hippocampal activation persistent across probe trials, and 2) a global superior activation of the dorsolateral striatum. Distinct patterns of Fos expression were therefore associated with every strain‐specific learning modality. In each strain, however, each modality was found to be remarkably stable, whatever the training duration and the cueing conditions. Hippocampus 2002;12:63–75. © 2002 Wiley‐Liss, Inc.
Early Head Start: A dynamic new program for infants and toddlers and their families
Authors: Raikes Helen H. , Love John M.
Published: October 2004

In just 6 years, Early Head Start has grown from 68 initial grantees to some 650 programs and, by early 2001, was serving more than 55,000 families with infants and toddlers throughout the country. With an increasing share of the federal Head Start budget, Early Head Start is an ambitious effort in which the Administration on Children, Youth and Families (ACYF) is responding to the “quiet crisis” facing infants and toddlers in this country, as identified by the Carnegie Corporation of New York in its 1994 Starting Points. This overview to the special issue of the journal describes the program, its growth, and the changing policy and program environment of its first 5 years; explains how the federal and regional infrastructure supports Early Head Start through training, technical assistance, and monitoring; summarizes the design and conduct of the national evaluation and local research studies; presents the key lessons that the research has yielded so far; and concludes with an assessment of the challenges that lie ahead for creating a solid base of knowledge for programs serving low‐income families with infants and toddlers. ©2002 Michigan Association for Infant Mental Health.
Improving child care quality in Early Head Start programs: A partnership model
Authors: Ontai Lenna L. , Hinrichs Sue , Beard Marti , Wilcox Brian L.
Published: October 2004

Many Early Head Start (EHS) programs do not provide child care directly but instead contract with existing community child care agencies to provide services. Such arrangements challenge EHS programs to create unique ways to ensure quality in the child care component of the program. The current research project reports on the efforts of a partnership between an EHS program and community child care agency to improve child care quality. The goal was to systematically identify changes in quality made within the EHS program as the result of a system of monitoring and assessment carried out under the partnership. The current study utilized ITERS and Arnett scales to assess the quality of the community center‐based infant child care at the beginning of the EHS program and nine months later. The results indicate a significant improvement in some areas of child care whereas other areas appeared to be more difficult to enhance with the current method. Additionally, differential areas of improvement were found between infant and toddler classrooms. The discussion focuses on aspects of the partnership that most likely contributed to quality improvements. ©2002 Michigan Association for Infant Mental Health.
Development of the shields for tendon injury repair using polyvinyl alcohol — hydrogel ( PVA‐H)
Authors: Kobayashi Masanori , Toguchida Junya , Oka Masanori
Published: October 2004

In recent years, marked advances have been made in repair techniques for tendon injury, but the treatment of finger flexor tendon injury is still one of the most difficult and important problems in the orthopedic field. The main problem in tendon repair is adhesion between the tendon and surrounding tissue. To prevent this adhesion and achieve tendon union, we developed adhesion preventive shields for tendon repair using polyvinyl alcohol hydrogel ( PVA‐H) with 90% water content, and carried out an implant experiment using the deep flexor tendon of the third toe of domestic fowl. Injured tendons shielded with PVA‐H showed union at about 3 weeks after the operation without adhesion to the surrounding tissue and good function such as gliding and range of motion. Neither breakage of the PVA‐H shield itself nor infection, nor degeneration in the surrounding tissue were observed. These results confirmed that the tendon itself has repair ability, and the tendon is regenerated by synovial nutrition through PVA‐H. High water content PVA‐H may have clinically potential and be applicable to adhesion‐preventive shields for tendon repair. However, re‐rupture was observed, probably due to accidental tendon injury at an early period after the operation. In some cases, tendon immobilization methods to prevent re‐rupture might be necessary. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 344–351, 2001
Blends of stearyl poly(ethylene oxide) coupling‐polymer in chitosan as coating materials for polyurethane intravascular catheters
Authors: Wang Dong‐An , Ji Jian , Sun Yong‐Hong , Yu Guan‐Hua , Feng Lin‐Xian
Published: October 2004

To optimize the surface biocompatibility of the intravascular catheter, an amphiphilic coupling‐polymer of stearyl poly (ethylene oxide) —co— 4,4'‐methylene diphenyl diisocyanate—co— stearyl poly (ethylene oxide), for short MSPEO, was specially designed as the surface modifying additive (SMA). The blend of MSPEO in chitosan was coated on the outer wall of the catheters by the dip‐coating method. The surface analysis was carried out by ATR‐FTIR and contact angle measurements. The surface enrichment of MSPEO was confirmed. On the water interface, the larger the molecular weight of PEO was, the higher the surface enrichment. While on air interface, the case was the contrary. Three kinds of static test of clotting time, plasma recalcification time (PRT), prothrombin time (PT), and thrombin time (TT), as well as the static platelet adhesion experiment were carried out. The results indicated that the coated surface could resist the clotting effectively. In order to test the blood‐compatibility of the coated catheters under a shear of blood flow, the dynamic experiment was performed through a closed‐loop tubular system with the shear rate of 1500 s−1. The results of blood regular testing at six different times (0, 5,10, 20, 30, and 60 min) indicated that the biocompatibility of the coating was nearly ideal. Finally, the SMA‐MSPEO was proved to be non‐chronic‐toxic by animal experiments with rats and suitable as a coating material for clinical use. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 372–383, 2001
Inhibition of leukotriene function can modulate particulate‐induced changes in bone cell differentiation and activity
Authors: Anderson Gail I. , MacQuarrie Robyn , Osinga Chris , Chen Ying Fang , Langman Maxine , Gilbert Robert
Published: October 2004

Aseptic loosening remains the major problem facing arthroplasty longevity with particulates from component materials touted as the cause of periprosthetic osteolysis. Proposed mechanisms in aseptic bone loss include: increased resorption, increased differentiation of osteoclasts (and/or macrophages locally), and decreased osteoblastic bone formation. Leukotrienes participate in osteoclastic bone resorption. We investigated inhibiting leukotrienes synthesis, using ICI 230487, to ameliorate the effects of particulates on osteoclast pit formation and also assessed the effects of alendronate, a bisphosphonate, on pit formation. Three particulates were used: ultra high molecular weight polyethylene (UHMWPE), polymethylmethacrylate (PMMA) and hydroxyapatite (HA). Osteoclast resorption was increased with UHMWPE, PMMA, and HA particles. Interventions with alendronate and ICI 230487 reduced particulate‐induced osteoclast resorption. Both ICI 230487 and alendronate reduced osteoclast numbers at higher doses. To assess the effect of particulates on osteoclast and macrophage differentiation, mouse bone marrow was cultured and stained for tartrate resistant acid phosphatase colonies (TRAP+, osteoclasts) and nonspecific esterase positive colonies (NSE+, macrophage precursors). Particulates increased both TRAP+ and NSE+ colony formation. These increases were inhibited by ICI 230487. Particulates also inhibited osteoblast function assessed by the development of mineralized nodules and alkaline phosphatase positive (AP+) colony area. ICI 230487 partly protected osteoblast function from this particulate effect. Blockade of leukotriene production may prove a useful therapeutic intervention for particulate‐induced aseptic loosening by inhibiting resorptive activity, reducing the pro‐inflammatory cell populations induced and recruited by these particulates, as well as ameliorating the negative effects of inflammatory mediators on osteoblast function.© 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 406–414, 2001
Effects of filler composition and surface treatment on the characteristics of opaque resin composites
Authors: Yoshida Keiichi , Tanagawa Mika , Atsuta Mitsuru
Published: October 2004

The effects of filler composition and surface treatment of titanium dioxide (TiO2) on the shear bond strength to noble metal and mechanical properties of opaque dental resin composites were assessed. A series of fillers for resin composites were prepared with untreated TiO2 or treated silica/alumina‐coated TiO2 with silane coupling agent; these fillers were replaced with silanized SiO2 in increasing amounts. Each of various powder compositions were mixed with the liquid and applied to the surface of a silver‐palladium‐copper‐gold (Ag‐Pd‐Cu‐Au) alloy and light cured. A light‐activated resin‐veneering composite material was placed on top with the use of a brass ring mold and light cured. Specimens were stored at 37 °C in water for a period of 24 h. Additionally some specimens were thermocycled at 4 °C and 60 °C in water baths for 1 min each for 5000 cycles before shear mode testing was performed. Light‐activated opaque resin composites containing filler with specific filler compositions of 50 wt% of untreated TiO2—50 wt% of silanized SiO2 (untreated TiO250) and 40 wt% of untreated TiO2—60 wt% of silanized SiO2 (untreated TiO240) showed higher shear bond strengths to the Ag‐Pd‐Cu‐Au alloy than any other specific compositions when no thermocycling was involved. Surface treatment of TiO2 filler and TiO250‐ and TiO240‐opaque resin composites prepared thereof showed significantly higher shear bond strengths than untreated TiO250‐ and TiO240‐opaque resin composites when subjected to thermocycling. Surface‐treated opaque resin composite had significantly higher compressive and flexural strength than untreated opaque resin composite after immersion in water for 1 month. Scanning electron microscopy of the fractured opaque resin composite surface showed an interface failure between TiO2 and the matrix resin for untreated composite, and cohesive failure within the resin for surface‐treated composite. Surface‐treated TiO250 and TiO240 may be clinically useful as the filler for light‐activated opaque dental resin composites. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 525–530, 2001
Relating nickel‐induced tissue inflammation to nickel release in vivo
Authors: Wataha John C. , O'Dell Norris L. , Singh Baldev B. , Ghazi Mohamed , Whitford Gary M. , Lockwood Petra E.
Published: October 2004

Nickel has a number of adverse biological effects that have made the use of nickel in biomedical implants controversial. Yet information about the distribution of nickel in tissues around nickel‐containing implants is scarce. The purpose of the current study was to use a laser ablation technique, combined with inductively coupled mass spectroscopy, to assess the spatial distribution of nickel around nickel‐containing implants in vivo. Polyethylene, pure nickel wire, or a nickel‐containing alloy (Ni‐Cr) were implanted subcutaneously into rats for 7 days. The tissues were analyzed for Ni content and inflammation at 1‐mm intervals up to 5 mm away from the implants. The sham surgery sites and the polyethylene caused mild to moderate inflammation 1–2 mm from the implant site with no detectable nickel in the tissue. The nickel wire caused severe inflammation up to 5 mm away from the implant site with necrosis for 1 mm around the implant. Nickel concentrations reached 48 μg/g near the implants, falling exponentially to undetectable levels at 3–4 mm from the implants. The Ni‐Cr wire caused inflammation equivalent to polyethylene, with less than 4 μg/g of nickel present in the tissue for 1–2 mm around the implants. The current study showed that the laser‐ablation technique was well suited for the analysis of soft tissues for metal‐ion content, and that the nickel distribution in tissues correlated well with overt tissue inflammation. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 537–544, 2001
Biofilm formation and design features of indwelling silicone rubber tracheoesophageal voice prostheses—an electron microscopical study
Authors: Leunisse Casper , van Weissenbruch Ranny , Busscher Henk J. , van der Mei Henny C. , Dijk Freark , Albers Frans W. J.
Published: October 2004

After total laryngectomy, voice can be restored with a silicone rubber tracheoesophageal voice prosthesis. However, biofilm formation and subsequent deterioration of the silicone material of the prosthesis will limit device life by impairing valve function. To simulate the natural process of biofilm development under dynamic nutrient conditions, a modified Robbins device was used to evaluate the biofilm‐related valve dysfunction of the Groningen, Provox2, Blom‐Singer indwelling, and VoiceMaster voice prostheses. Obstruction of the semicircular slit‐valved Groningen prosthesis leading to increased airway resistance was caused not only by a buildup of deposits on the esophageal flange and valve hat, but also by accumulation of deposits on the semicircular valve seating. The hinged flap valved Provox2 and indwelling Blom‐Singer prostheses failed to close sufficiently because of biofilm formation on the valve seating. The esophageal flange of the VoiceMaster prosthesis was affected, but the tripod structure of the ball valve was fully colonized up to the titanium sleeve, which interfered with proper valve opening and closure. These findings on biofilm formation could be used for the further development and modification of critical design features of voice prostheses to facilitate tracheoesophageal speech. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 556–563, 2001
Comparative analysis of the structure and thermal stability of sea urchin peristome and rat tail tendon collagen
Authors: Mayne Janice , Robinson John J.
Published: October 2004

We have purified collagen from two distinct sources; the vertebrate, rat tail tendon and an invertebrate, sea urchin adult tissue, the peristome. The collagenous nature of the purification products was confirmed by amino acid compositional analysis. Both preparations had high contents of glycine and proline residues and hydroxyproline was also present. The total pyrrolidine (proline + hydroxyproline) content decreased from 17.9 mole % in rat tail collagen to 12.9 mole % in peristome collagen. Distinctly different circular dichroic spectra were measured for these collagens. Analyses of spectra, measured as a function of temperature, revealed distinct thermal denaturation profiles. The melting temperature for rat tail collagen was 38.5°C, while the corresponding value for peristome collagen was significantly lower at 27°C. A similar thermal denaturation profile was obtained for rat tail collagen in digestion experiments using a 41‐kDa gelatinase activity, isolated from sea urchin eggs. These results identify structural differences between a typical, vertebrate type I fibrillar collagen and an echinoderm collagen which serves as a constituent of a mutable connective tissue. These differences may relate to the functional roles played by collagen in these distinctly different tissues. J. Cell. Biochem. 84: 567–574, 2002. © 2001 Wiley‐Liss, Inc.
Orphan nuclear receptor binding site in the human inducible nitric oxide synthase promoter mediates responsiveness to steroid and xenobiotic ligands
Authors: Toell Andrea , Kröncke Klaus‐Dietrich , Kleinert Hartmut , Carlberg Carsten
Published: October 2004

Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are members of the nuclear receptor superfamily that regulate target gene transcription in a ligand‐dependent manner. CAR and PXR have a rather broad, overlapping set of ligands that range from natural steroids to xenobiotics and also recognize similar DNA binding sites, referred to as response elements (REs), primarily in promoter regions of cytochrome P450 (CYP) genes. In this study, a CAR and PXR RE, composed of a direct repeat of two GGTTCA motifs in a distance of 4 nucleotides (DR4), was identified in the promoter of the human inducible nitric oxide (NO) synthase (iNOS ) gene, which is the first nuclear receptor binding site reported for this promoter. In a heterologous promoter context, the DR4‐type sequence also acts as a functional RE for the nuclear receptors for 1α,25‐dihydroxyvitamin D3 (1α,25(OH)2D3) and 3,5,3′‐triiodothyronine (T3), VDR and T3R. However, in a direct competition of CAR, PXR, VDR, and T3R, the PXR‐retinoid X receptor (RXR) complex appears to be the dominant regulator on the iNOS DR4‐type RE. In the natural iNOS promoter context, the DR4‐type RE specifically mediates downregulation of promoter activity by the testosterone metabolite androstanol through CAR‐RXR heterodimers and upregulation by the xenobiotic drug clotrimazole through PXR–RXR heterodimers. These results were confirmed on the level of mRNA expression. Since an iNOS‐induced production of NO is known to influence inflammation and apoptosis, a CAR‐ and PXR‐regulated iNOS activity may explain a modulatory effect of steroids and xenobiotics on these cellular processes. J. Cell. Biochem. 85: 72–82, 2002. © 2002 Wiley‐Liss, Inc.
Interaction of the ADP‐ribosylating enzyme from the hyperthermophilic archaeon S. solfataricus with DNA and ss‐oligo deoxy ribonucleotides
Authors: Faraone‐Mennella Maria Rosaria , Piccialli Gennaro , De Luca Paola , Castellano Sabrina , Giordano Anna , Rigano Daniela , De Napoli Lorenzo , Farina Benedetta
Published: October 2004

The DNA‐binding ability of the poly‐ADPribose polymerase‐like enzyme from the extremely thermophilic archaeon Sulfolobus solfataricus was determined in the presence of genomic DNA or single stranded oligodeoxyribonucleotides. The thermozyme protected homologous DNA against thermal denaturation by lowering the amount of melted DNA and increasing melting temperature. The archaeal protein induced structural changes of the nucleic acid by modifying the dichroic spectra towards a shape typical of condensing DNA. However, enzyme activity was slightly increased by DNA. Competition assays demonstrated that the protein interacted also with heterologous DNA. In order to characterize further the DNA binding properties of the archaeal enzyme, various ss‐oligodeoxyribonucleotides of different base composition, lengths (12‐mer to 24‐mer) and structure (linear and circular) were used for fluorescence titration measurements. Intrinsic fluorescence of the archaeal protein due to tryptophan (excitation at 295 nm) was measured in the presence of each oligomer at 60°C. Changes of tryptophan fluorescence were induced by all compounds in the same range of base number per enzyme molecule, but independently from the structural features of oligonucleotides, although the protein exhibited a slight preference for those adenine‐rich and circular. The binding affinities were comparable for all oligomers, with intrinsic association constants of the same order of magnitude (K = 106 M−1) in 0.01 M Na‐phosphate buffer, pH 8.0, and accounted for a “non‐specific” binding protein. Circular dichroism analysis showed that at 60°C the native protein was better organized in a secondary structure than at 20°C. Upon addition of oligonucleotides, enzyme structure was further stabilized and changed towards a β‐conformation. This effect was more marked with the circular oligomer. The analysed oligodeoxyribonucleotides slightly enhanced enzyme activity with the maximal increase of 50% as compared to the control. No activation was observed with the circular oligomer. J. Cell. Biochem. 85: 146–157, 2002. © 2002 Wiley‐Liss, Inc.
Cytokine regulatory effects on α‐1 proteinase inhibitor expression in NOD mouse islet endothelial cells
Authors: Papaccio Gianpaolo , Pedullà Marcella , Ammendola Eduardo , Todaro Matilde
Published: October 2004

Human microvascular islet endothelial cells (IEC) exhibit specific morphological and functional characteristics that differ from endothelia derived from other organs. One of these characteristics is the expression of α‐1 proteinase inhibitor (Api). In this study, we observed its expression in nonobese diabetic (NOD) mouse IEC, in relation to the occurrence of type 1 diabetes and in response to cytokines, namely IL‐1β and IL‐10. In addition, IL‐10‐deficient NOD mice as well as IL‐10 transgenic NODs were studied. Results have demonstrated that Api expression is: (i) highly specific for IEC in NOD mouse islets, as for humans; (ii) linked to the occurrence of early type 1 diabetes, and iii) strongly modulated by Th1 and Th2 cytokines. In fact, Api mRNA found in pre‐diabetic NOD animals is significantly reduced when they become hyperglycemic and disappears by 25 weeks of age, when mice are diabetic. Moreover, Api mRNAs are never seen in nondiabetic controls. Furthermore, in cultured NOD IEC, Api expression is downregulated by the addition of IL‐1β and is upregulated by IL‐10; it is always absent in IL‐10‐deficient NOD mice and overexpressed in IL‐10 transgenic NODs, thus further supporting that this cytokine upregulates Api expression. J. Cell. Biochem. 85: 123–130, 2002. © 2002 Wiley‐Liss, Inc.
Theoretical auger electron spectra of polymers by density functional theory calculations using model dimers
Authors: Otsuka Takao , Koizumi Seiji , Endo Kazunaka , Kawabe Hiroyuki , Chong Delano P.
Published: October 2004

We propose a new approach for analysis of Auger electron spectra (AES) of polymers by density functional theory (DFT) calculations with the Slater's transition‐state concept. Simulated AES and X‐ray photoelectron spectra (XPS) of four polymers [(CH2CH2)n (PE), (CH2CH(CH3))n (PP), (CH2CH(OCH3))n (PVME), and (CH2CH(COCH3))n (PVMK)] by DFT calculations using model dimers are in a good accordance with the experimental ones. The experimental AES of the polymers can be classified in each range of 1s–2p2p, 1s–2s2p, and 1s–2s2s transitions for C KVV and O KVV spectra, and in individual contributions of the functional groups from the theoretical analysis. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 394–401, 2002
Solvated ensemble averaging in the calculation of partial atomic charges
Authors: Basma M. , Sundara S. , Çalgan D. , Vernali T. , Woods R. J.
Published: October 2004

In the calculation of partial atomic charges, for use in molecular mechanics or dynamics simulations, it is common practice to select only a single conformation for the molecule of interest. For molecules that contain rotatable bonds, it is preferable to compute the charges from several relevant conformations. We present here results from a charge derivation protocol that determines the partial charges by averaging charges computed for conformations selected from explicitly solvated MD simulations, performed under periodic boundary conditions. This approach leads to partial charges that are weighted by a realistic population of conformations and that are suitable for condensed phase simulations. This protocol can, in principle, be applied to any class of molecule and to nonaqueous solvation. Carbohydrates contain numerous hydroxyl groups that exist in an ensemble of orientations in solution, and in this report we apply ensemble averaging to a series of methyl glycosides. We report the extent to which ensemble averaging leads to charge convergence among the various monosaccharides and among the constituent atoms within a given monosaccharide. Due to the large number of conformations (200) in our ensembles, we are able to compute statistically relevant standard deviations for the partial charges. An analysis of the standard deviations allows us to assess the extent to which equivalent atom types may, nevertheless, require unique partial charges. The configurations of the hydroxyl groups exert considerable influence on internal energies, and the limits of ensemble averaged charges are discussed in terms of these properties. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1125–1137, 2001
OH hydrogen abstraction reactions from alanine and glycine: A quantum mechanical approach
Authors: Galano Annia , Alvarez‐Idaboy J. Raúl , Montero Luis A. , Vivier–Bunge Annik
Published: October 2004

Density functional theory (B3LYP and BHandHLYP) and unrestricted second‐order Møller–Plesset (MP2) calculations have been performed using 3‐21G, 6‐31G(d,p), and 6‐311 G(2d,2p) basis sets, to study the OH hydrogen abstraction reaction from alanine and glycine. The structures of the different stationary points are discussed. Ring‐like structures are found for all the transition states. Reaction profiles are modeled including the formation of prereactive complexes, and very low or negative net energy barriers are obtained depending on the method and on the reacting site. ZPE and thermal corrections to the energy for all the species, and BSSE corrections for B3LYP activation energies are included. A complex mechanism involving the formation of a prereactive complex is proposed, and the rate coefficients for the overall reactions are calculated using classical transition state theory. The predicted values of the rate coefficients are 3.54×108 L⋅mol−1⋅s−1 for glycine and 1.38×109 L⋅mol−1⋅s−1 for alanine. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1138–1153, 2001
Solvation in octanol: parametrization of the continuum MST model
Authors: Curutchet Carles , Orozco Modesto , Luque F. Javier
Published: October 2004

This study reports the parametrization of the HF/6‐31G(d) version of the MST continuum model for n‐octanol. Following our previous studies related to the MST parametrization for water, chloroform, and carbon tetrachloride, a detailed exploration of the definition of the solute/solvent interface has been performed. To this end, we have exploited the results obtained from free energy calculations coupled to Monte Carlo simulations, and those derived from the QM/MM analysis of solvent‐induced dipoles for selected solutes. The atomic hardness parameters have been determined by fitting to the experimental free energies of solvation in octanol. The final MST model is able to reproduce the experimental free energy of solvation for 62 compounds and the octanol/water partition coefficient (log Pow) for 75 compounds with a root‐mean‐square deviation of 0.6 kcal/mol and 0.4 (in units of log P), respectively. The model has been further verified by calculating the octanol/water partition coefficient for a set of 27 drugs, which were not considered in the parametrization set. A good agreement is found between predicted and experimental values of log Po/w, as noted in a root‐mean‐square deviation of 0.75 units of log P. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1180–1193, 2001
When anomeric effects collide
Authors: Cramer Christopher J. , Kelterer Anne‐Marie , French Alfred D.
Published: October 2004

Rotational coordinates about the C(3)–O(4) bonds of 2,4‐dioxaheptane (DOH) and 2,4,6‐trioxaheptane (TOH) are compared at correlated levels of electronic structure theory for gauche and trans orientations of the O(2)–C(3) bonds. TOH has overlapping anomeric effects, while DOH does not. The overlapping stereoelectronic effect shows its largest impact on the length of the O(2)–C(3) bond, which is typically 0.02 Å longer in DOH than in TOH. However, the energetic consequences of the overlapping anomeric effect in TOH are very small, as judged by total conformational energies and analysis of delocalization energies within a natural bond orbital framework. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1194–1204, 2001
The cognitive neuroscience paradigm: A unifying metatheoretical framework for the science and practice of clinical psychology
Authors: Ilardi Stephen S. , Feldman David
Published: October 2004

The emerging discipline of cognitive neuroscience (CN) enjoins the efforts of cognitive psychologists, neuroscientists, computer scientists, clinical neurologists, neurophilosophers, and many others working collaboratively across traditional disciplinary boundaries to elucidate the manner in which the physical operations of the brain give rise to the vast panoply of human mental and behavioral events. The present article describes the foundational tenets of the CN metatheoretical framework and contends that the CN framework is capable of providing a coherent, unifying scientific paradigm for the discipline of clinical psychology. Clinical psychology's adoption of the CN paradigm would facilitate (a) its consilient linkage with the natural sciences, (b) resolution of long‐standing internecine theoretical schisms, and (c) enhanced understanding and treatment of numerous forms of psychopathology. Nevertheless, psychology's historically influential radical behavioral (RB) perspective is not easily reconciled with the CN paradigm. However, unlike CN, RB (a) is not fully consilient with the natural sciences, (b) fails to articulate the proximal causal mechanisms that mediate environment–behavior relations, and (c) engages in “greedy reductionism” in its disavowal of informational levels of complexity in the patterning of neural activity. The article concludes with a discussion of the possibility of theoretical rapprochement between CN and RB. © 2001 John Wiley & Sons, Inc. J Clin Psychol 57: 1067–1088, 2001.
Loss of functional caveolae during senescence of human fibroblasts
Authors: Wheaton Keith , Sampsel Kari , Boisvert Francois‐Michel , Davy Alice , Robbins Stephen , Riabowol Karl
Published: October 2004

Primary human fibroblasts have a finite replicative lifespan in culture that culminates in a unique state of growth arrest, termed senescence that is accompanied by distinct morphological and biochemical alterations. Senescent cell responses to extracellular stimuli are believed to be altered at a point after receptors are bound by ligand, leading to improper integration of the signals which initiate DNA replication. In this study we demonstrate that one of the key organizing membrane microdomains for receptor signaling, caveolae, are absent in senescent cells. A comparison of young and senescent cells indicated that senescent cells contained a higher total amount of caveolins 1 and 2 but had significantly less of both proteins in the caveolar fraction. Additionally, caveolar fractions from senescent cells completely lacked the tyrosine‐kinase activity associated with functional caveolae. Furthermore, old cells had little caveolar protein exposed to the outer plasma membrane as estimated by using an in vivo biotinylation assay and no detectable caveolin 1 on the cell surface when processed for immunofluoresence and confocal microscopy. Together, these data suggest that a fundamental loss of signal integration at the plasma membrane of senescent cells is due to the loss of signaling competent caveolae. © 2001 Wiley‐Liss, Inc.
Sonographic features of xanthogranulomatous pyelonephritis
Authors: Tiu Chui‐Mei , Chou Yi‐Hong , Chiou Hong‐Jen , Lo Chao‐Bao , Yang Jin‐Yi , Chen Kwang‐Kuo , Hsu Ming‐Hui , Wang Jia‐Hwia , Su Yeou‐Gyi , Chang Cheng‐Yen , Yu Chun
Published: October 2004

Purpose

The purpose of this study was to describe the various sonographic features of xanthogranulomatous pyelonephritis (XGP).

Methods

We retrospectively reviewed the CT, sonographic, and medical records of patients diagnosed with XGP from January 1981 to December 1998. Twenty‐seven patients for whom XGP was histopathologically confirmed were included in the study. There were 12 men and 15 women, with an age range of 21–86 years (mean, 57 years). All patients had undergone sonography of the kidneys. The renal size, shape, and outline were recorded. The presence of perinephric fluid accumulation, of obstructive uropathy, or of internal echoes in the dilated collecting system and the echotexture of the renal parenchyma were documented.

Results

We categorized the XGP into 4 groups on the basis of the sonographic features: (1) diffuse hydronephrotic, 12 patients (44%); (2) diffuse parenchymal, 9 patients (33%); (3) diffuse contracted, 4 patients (15%); and (4) segmental or focal, 2 patients (7%). A localized perinephric fluid collection was present in 4 patients (15%). The preoperative sonographic diagnoses were pyonephrosis (n = 14, 52%), renal pelvic tumor with possible associated infection (n = 5, 19%), renal parenchymal mass (n = 2, 7%), hydronephrosis (n = 2, 7%), and chronic pyelonephritis with renal atrophy (n = 4, 15%). XGP was considered a possible diagnosis in only 11 patients (41%).

Conclusions

XGP has no specific sonographic features but is suggested by parenchymal thinning and hydronephrosis, sonographic signs of chronic obstructive uropathy caused by stones; echoes in the dilated collecting system; and a perinephric fluid collection. CT, needle biopsy, or both are recommended to further evaluate and confirm sonographically suspected XGP. © 2001 John Wiley & Sons, Inc. J Clin Ultrasound 29:279–285, 2001.
Sonographic evaluation of gallbladder‐wall thickening in hemorrhagic fever with renal syndrome: Prediction of disease severity
Authors: Kim Young Ok , Chun Kyung Ah , Choi Jee Youn , Yoon Sun Ae , Yang Chul Woo , Kim Ki Tae , Bang Byung Kee
Published: October 2004

Purpose

Gallbladder‐wall thickening (GBWT) frequently occurs in patients with hemorrhagic fever with renal syndrome (HFRS), an acute infectious disease caused by hantaviruses. HFRS is manifested by fever, hemorrhage, renal failure, and in many cases gastrointestinal symptoms, such as abdominal pain and tenderness. The clinical significance of GBWT in HFRS has not been reported. The purpose of this study was to investigate the incidence of GBWT and the relationship between GBWT and the severity of HFRS.

Methods

We retrospectively reviewed the medical records and sonograms of 68 patients with HFRS (47 males and 21 females, with an age range of 10–76 years) who underwent abdominal sonography in the acute stage of the disease. We measured the gallbladder‐wall thickness on the sonograms and reviewed other sonographic and radiographic findings. Clinical factors that reflect the severity of HFRS were compared between the patients with GBWT (defined as thickness of 4 mm or more) and those without GBWT.

Results

Of the 68 patients, 29 (43%) had GBWT, which was even and diffuse in all cases. The patients with GBWT had a significantly lower mean platelet count and serum albumin level and significantly higher serum aspartate aminotransferase and serum lactate dehydrogenase levels than did the patients without GBWT. In addition, the incidence of renal failure requiring hemodialysis and the incidences of ascites and pleural effusion were higher in the patients with GBWT than in those without GBWT. Five patients died of HFRS; all 5 had GBWT (p = 0.011 for comparison with patients without GBWT).

Conclusions

Our results suggest that the sonographic measurement of gallbladder‐wall thickness during the acute stage of HFRS is useful for determining the severity of HFRS. © 2001 John Wiley & Sons, Inc. J Clin Ultrasound 29:286–289, 2001.