bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-operative radiation therapy for advanced-stage oropharyngeal cancer
Authors: Hansen Eric , Panwala Kathryn , Holland John
Published: January 2003

Between 1985 and 1999, 43 patients with locally-advanced, resectable oropharyngeal cancer were treated with combined surgery and post-operative radiation therapy (RT) at Oregon Health and Science University. Five patients (12 per cent) had Stage III disease and 38 patients (88 per cent) had Stage IV disease. All patients had gross total resections of the primary tumour. Thirty-seven patients had neck dissections for regional disease. RT consisted of a mean tumour-bed dose of 63.0 Gy delivered in 1.8–2.0 Gy fractions over a mean of 49 days. At three- and five-years, the actuarial local control was 96 per cent and the actuarial local/regional control was 80 per cent. The three- and five-year actuarial rates of distant metastases were 41 per cent and 46 per cent, respectively. The actuarial overall survival at three- and five-years was 41 per cent and 34 per cent, respectively. The actuarial rates of progression-free survival were 49 per cent at three-years and 45 per cent at five years. Combined surgery and post-operative RT for advanced-stage oropharyngeal cancer results in excellent local/regional control. This particular group of patients experienced a high-rate of developing distant metastases.
Cervical node metastases in oropharyngeal squamous cell carcinoma: prospective analysis of prevalence and distribution
Authors: Jose Jemy , Coatesworth Andrew P. , Johnston Colin , MacLennan Ken
Published: January 2003

The treatment of cervical lymph node metastases is an important part of the management of oropharyngeal squamous cell cancer. Metastases are already clinically present in 61 per cent (+ or −2.6 per cent) of patients at presentation. Previous studies concerning the prevalence and distribution of neck node metastases in oropharyngeal carcinoma have been retrospective, and little or no information is available about the histopathological methods used.

This study has prospectively analysed 85 neck dissection specimens in 72 consecutive patients with squamous cell carcinoma of the oropharynx, both with clinically N0 and N+ve necks, to identify the prevalence and distribution of cervical metastases. We have used a technique to separate the neck dissection into nodal levels per-operatively, and then embedded the entire specimen for histological examination to avoid missing metastatic disease in small lymph nodes (<3mm diameter).
Microvascular free tissue reconstruction following extirpation of head and neck tumour: experience towards an optimal outcome
Authors: Lam L. K. , Wei William I. , Chan Vana S. H. , Ng Raymond W. M. , Ho W. K.
Published: January 2003

Familiarity with four types of free tissues transfers allows appropriate reconstruction of most defects in the head and neck region functionally and aesthetically. These include jejunal graft, radial forearm, rectus abdominus myocutaneous and fibula osteocutaneous flaps. Free colonic and gastric patches were used occasionally.

We report our experience of 215 free tissue transfers for reconstruction of defects in the head and neck region after tumour extirpation.

The overall success rate was 94 per cent. The commonest cause of failure was related to arterial inflow (70 per cent). Three patients died in hospital, but their mortality was not related to the tissue transfers. Complications due to free tissue transfer at both the donor and recipient sites were few and manageable.

The co-operation between the two surgical teams, together with the timely application of suitable salvage procedures, contribute to an optimal outcome.
Endoscopic sinus surgery for sinonasal haemangiopericytomas
Authors: Serrano E. , Coste A. , Percodani J. , Hervé S. , Brugel L.
Published: January 2003

Haemangiopericytomas are rare peri-vascular tumours with variable malignant potential. The nasal cavity and the paranasal sinuses are most often involved in the head and neck. Five cases of haemangiopericytomas treated by a strict endonasal endoscopic approach are presented. Bleeding and nasal obstruction are the most frequent symptoms. Computed tomography (CT) scan and magnetic resonance imaging (MRI) allowed pre-operative assessment. Angiography with embolization was needed in two of the five cases. None of our patients presented with malignant histology. Our five cases were operated on, and a total tumour excision was performed through the endoscopic endonasal approach. We had one recurrence with a mean follow-up of 4.5 years. We suggest that when the tumour is purely intranasal or strictly located in the ethmoid or sphenoid sinus, it can be removed via an endonasal approach under endoscopic guidance in experienced hands.
Intractable paroxysmal sneezing
Authors: Gopalan Pushkas , Browning Simon T.
Published: January 2003

Intractable paroxysmal sneezing is a rare disease primarily affecting teenage girls. We present the case of a 12-year-old girl who demonstrated the classical features of intractable paroxysmal sneezing of psychogenic origin. Most of the reported cases are psychogenic in origin, but a number of other conditions may cause intractable paraoxysmal sneeze. Apart from a detailed history, clinical examination and relevant investigations, topical nasal anaesthesia should be tried for control of symptoms – that will help to differentiate psychogenic sneezing from organic sneezing. A timely diagnosis can avoid unnecessary medical trials, parental anxiety and poor school performance, as most of the patients are very young.
Solitary plasmacytoma and extramedullary plasmacytoma of the paranasal sinuses and soft palate
Authors: Majumdar S. , Raghavan U. , Jones N. S.
Published: January 2003

Solitary plasmacytoma of the paranasal sinuses are uncommon neoplasms of B lymphocyte origin. They comprise one per cent of all head and neck tumours of the upper respiratory tract. They can be solitary plasmacytomas of the bone (SPB), an extramedullary plasmacytoma or a local manifestation of multiple myeloma. Conversion to multiple myeloma happens more frequently in SPB. Radiotherapy is the common modality of treatment with, or without, adjuvant chemotherapy. Extramedullary plasmacytoma carries a better prognosis than a solitary plasmacytoma of the bone. We report four cases of solitary plasmacytoma of the bone and an extramedullary plasmacytoma of the paranasal sinuses and soft palate.
Limited form of Churg-Strauss syndrome presenting as a mass in the neck
Authors: Moor J. W. , Im J. U-King , MacDonald A. W. , Whitehead E.
Published: January 2003

A 53-year-old man was referred to the ENT department with a large mass in the left supraclavicular fossa. The histological diagnosis showed the mass to have arisen due to a granulomatous vasculitis consistent with Churg-Strauss syndrome (CSS). CSS usually comprises asthma, eosinophilia and systemic vasculitis although limited forms of the disease exist where one of these diagnostic criteria is missing. This is one such case as the patient was non-asthmatic.
Will Natural Gas Supply Meet the Demand in North America?
Authors: Laherrere Jean
Published: January 2003

The goal of this paper is to deliver to the reader a large number of graphs in order to allow him to choose the ones that he considers important to make his own opinion. Graphs from data are more important than statements, which are mainly interpretations and political. The main problem is that the data are fairly unreliable. This paper assess the various components in order to provide a compendium of behaviours for future use in strategic and tactical planning for gas energy needs.
Iterative Model for the Performance Evaluation of a Horizontal Axis Wind Turbine
Authors: Mahapatra Sadhan , Neogi Subhasis
Published: January 2003

This paper is based on the studies made on a numerical model for calculating the turbine characteristics at low tip speed ratio for a Horizontal Axis Wind Turbine. The turbine characteristics are analysed for different configurations over the total operating range i.e. from tip speed ratio of zero to a maximum value where CP becomes zero. The simulation model provides acceptable results, however for the blade position near the hub, a non-convergent situation is observed i.e. the flow parameters converge to values outside those associated with turbine operation. This indicates the possibility of a multisolution.
Technical Note: Comparison of the Sound Insulation of Lightweight Partitions with Different Sound Absorbing Infills
Authors: Bravo Jose Maria , Estelles Hermelando , Llinares Jaime , Sinisterra Jaime , Uris Antonio
Published: January 2003

Measurements of sound reduction indices for lightweight gypsum board partitions filled with three different sound absorbing materials (rockwool, glasswool and polyurethane foam) are reported. For partitions where the gypsum panels are mounted on a common stud, with the sound absorbing infill in direct contact with both panels and for uncoupled double partitions, measurement results show that polyurethane foam, of high flow resistivity and stiffness, is less effective as an infill than either rockwool or glasswool.
The Prediction of Reverberation Time Using Optimal Neural Networks
Authors: Nannariello Joseph , Fricke Fergus
Published: January 2003

A neural network approach to predicting the reverberation time, RT60, at the conceptual design stage of auditoria, and churches is presented. The results of investigations previously carried out indicated that there was a good basis for using trained neural networks to predict the reverberation time for unoccupied enclosures but that 15 input variables were required to achieve the desired accuracy. As the number of input variables that can be readily identified and quantified at the early design stage is small, the objective of this work is to reduce network size and to obtain optimal neural networks. The results showed that the generalization performance of neural networks with simplified internal representation is efficient. Generally, the reverberation time prediction accuracy of the network models, for the six enclosures ‘tested’, is within the range of the subjective difference limen (ΔT/T ≈ 5%).
Hybrid Stress Finite Element Methods for Plate and Shell Structures
Authors: Pian Theodore H. H. , Sze Kam-Yim
Published: January 2003

This paper is a survey of the use of assumed stress hybrid finite element methods for analyzing plate and shell structures. It describes the construction of Kirchhoff plate element by complementary energy principle, and of Reissner-Mindlin plate element by Hellinger-Reissner principle. Special hybrid stress elements are used to model joining of elements which are not coplanar. Such elements include the so-called semiLoof plate elements and 3D-solid elements tailored for analyzing thin plates and shells.
Preliminary Fatigue Tests on Concrete Exposure to Temperature of up to 300°C
Authors: Zhou Xingang , Zhang John
Published: January 2003

Micro-cracks in the vicinity of paste-aggregate interfaces and in the paste itself can be induced when concrete is exposed to elevated temperatures in the range 100°C-300°C. Although with increase of temperature, the strength of concrete becomes more and more influenced by the growing number of micro-cracks, the compressive strength of concrete at an elevated temperature lower than 300°C is almost the same of concrete at room temperature. Under repeated load, those microcracks caused by temperature would propagate, enlarge and become linked up, as a result, the fatigue behavior of concrete would decrease. In this paper, tests have been carried out to study the fatigue behavior of concrete after exposure to elevated temperatures of up to 300°C. Test results have shown that the reduction of fatigue strength of concrete is remarkable.
The Stability of Weakly Braced Frames
Authors: Gengshu Tong , Zuyuan Shi
Published: January 2003

This paper reports an investigation into the buckling of frames with braces whose stiffness is insufficient to prevent sway buckling. Formulae are presented to calculate the effective column length for these weakly braced frames. Threshold stiffness values for the braces are obtained which are just enough to make frame buckle in a non-sway mode. After taking the influence of initial imperfection and lateral loads into account the brace threshold stiffness may be used as a rational basis for classifying sway frames and non-sway frames.
Application of EBEF Method for the Distortional Analysis of Steel Box Girder Bridge Superstructures during Construction
Authors: Hsu Yao T. , Fu Chung C.
Published: January 2003

For curved steel box girder bridges, loads applied away from the shear center of the box can be separated into bending and torsional components. Associated with these flexural and torsional loads are three normal stresses, four shear stresses, and one bending stress. The least understood stresses are stresses (normal distortional warping stress, distortional warping shear stress and distortional transverse bending stress) associated with distorsion of the box cross section. By the addition of steel diaphragms, distortional stresses can be decreased. A practical approach to the distortional analysis of steel box girder bridge superstructures during construction is presented in this paper. The EBEF (equivalent beam on elastic foundation) method is an enhancement of the BEF (beam on elastic foundation) method, which has been widely used in design practice. Also presented herein are methodologies and results of numerical examples in comparison with the finite strip method.
Cracking in a Curved, Reinforced Concrete Box Girder Bridge
Authors: Fu Yongda , DeWolf John T.
Published: January 2003

A study to monitor a multi-span reinforced concrete bridge was recently completed. The bridge is curved, with a non-prismatic three-cell box cross section. Extensive field testing was performed to evaluate the causes and effects of large shear cracks. Evaluation of the test results has shown that the distribution of strains in the bridge is significantly different from those assumed in design. This paper reports on the use of finite element analysis to assist in the evaluation of the behavior. Of prime interest has been the identification of the sources of the discrepancy between the test data and the design. This work shows that it is necessary to include concrete softening due to both shear and flexural cracking. The finite element model has also been used to demonstrate that the cracks were primarily the result of temperature differentials arising from the position of the sun during the normal daily cycle.
Synthesis and molecular structure of 2,4,6‐tri[bis(diisopropylamino)boryl(methylamino)]borazine, [(NiPr2)2B(Me)N]3B3N3H3
Authors: Toury Bérangère , Cornu David , Lecocq Sylvain , Miele Philippe
Published: January 2003

Reaction of bis(diisopropylamino)(methylamino)borane, (NHiPr)2B(NHMe), with 2,4,6‐trichloroborazine (ClBNH)3 affords 2,4,6‐tri[bis(diisopropylamino)boryl(methylamino)]borazine, 2,4,6‐[(NiPr2)2B(Me)N]3B3N3H3, which is the first boryl‐borazine structurally characterized. According to the X‐ray single crystal structure and the chemical shifts of 11B NMR resonances of boron atoms, compared with the aminoborane and borazine analogs, the borazine and boryl π‐systems are not coplanar either in the solid state or in organic solution. Copyright © 2002 John Wiley & Sons, Ltd.
Order–disorder phenomena in crystalline phases of compounds E(XMe3)4 where E = C, Si, Ge and X = Si, Sn
Authors: Helluy Xavier , Sebald Angelika
Published: January 2003

We discuss the dynamic solid‐state properties of crystalline phases E(XMe3)4 as seen by solid‐state NMR and powder X‐ray diffraction. In the first part we will qualitatively describe some of the NMR tools suitable for such investigations. In the second part we will give examples from the group of solid compounds E(XMe3)4 with E = C, Si, Ge and X = Si, Sn. Copyright © 2002 John Wiley & Sons, Ltd.
Effect of crystallization conditions on spherulitic texture and tensile properties of sPS/PPO blends
Authors: Dutt G. , Kit K. M.
Published: January 2003

In the second study on melt‐miscible syndiotactic polystyrene (sPS) and poly(phenylene oxide) (PPO) blends, the effect of processing conditions on morphology, ultimate tensile properties, and the mode of fracture is reported. Bulk samples of the blends were molded and then crystallized from melt as well as from the quenched state at different temperatures. The spherulitic morphology of the melt‐crystallized blends, observed by scanning electron microscopy, revealed formation of complete, well‐developed spherulites whose texture increased in coarseness with increasing crystallization temperatures. In all the cold‐crystallized blends lamellar bundles formed a meshlike structure whose texture did not vary significantly with crystallization temperature. Depending on the crystallization temperature, 50/50 melt‐crystallized blends showed varying tensile properties and different modes of failure. In the samples with the largest amorphous domain size of 0.6 μm, the amorphous ellipsoids were cold drawn into fibrils during tensile loading and very high tensile strengths were recorded. The tensile properties for the other melt‐crystallized and all cold‐crystallized blends did not vary substantially with the changing crystallization temperature. The micrographs of the fractured surfaces of the melt‐crystallized blends suggested that, although intraspherulitic fracture occurred at low crystallization temperatures, interspherulitic fracture took place at high crystallization temperatures. The correlation of the morphology and mechanical properties suggests that melt‐miscible blends have good interfacial adhesion between phases and that, by varying composition and processing conditions, it might be possible to control amorphous domain sizes, which is critical in achieving better mechanical properties. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1984–1994, 2003
Kinetics of hydrolysis of polyethylene terephthalate pellets in nitric acid
Authors: Kumar Aanchal , Rao T. Rajeswara
Published: January 2003

The hydrolysis of polyethylene terephthalate (PET) pellets in nitric acid was investigated to determine the kinetic parameters. Experiments were conducted with cylindrical shaped pellets in 13M nitric acid at 80, 90, and 100°C respectively. Also, an experiment was conducted with a waste PET bottle sheet in 9.5M nitric acid at 100°C. The kinetics of the reaction was explained by the shrinking core model with surface chemical reaction as rate controlling step and accounting for surface area reduction due to the deposition of the product terephathalic acid (TPA) on the reaction surface. The activation energy for the reaction was found to be 135 kJ/mol. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 87:1781–1783, 2003
Reaction and miscibility of two diepoxides with poly(ethylene terephthalate)
Authors: Fenouillot Françoise , Hedreul Claire , Forsythe John , Pascault Jean‐Pierre
Published: January 2003

Poly(ethylene terephthalate) (PET) was melt‐blended at 270°C with two epoxy monomers, diglycidyl ether of bisphenol A (DGEBA) and 3,4‐epoxycyclohexyl‐methyl‐3,4‐epoxycyclohexyl carboxylate (ECY). Intermediate proportions of the epoxy in the range of 20–0.5 wt % were used. If the epoxy monomers were added in a high proportion (10–20%), a large fraction did not react with PET. Calorimetric experiments showed that the unreacted fractions of both epoxies were miscible with the amorphous phase of the polyester. Only one glass‐transition temperature was detected. It was depressed as the epoxy content was increased. The transition was broad when the PET component was crystalline, and it was narrow when the PET component was made amorphous by quenching of the blend. These features were confirmed by dynamic thermal mechanical analysis. As is often the case for crystalline blends, the crystallization and melting temperatures decreased when the proportion of the epoxy was increased. Concerning the reactivity of the epoxy with PET, the behavior differed according to the nature of the epoxy. The DGEBA monomer showed a low reactivity. It was not effective for the chain extension of PET, and no increase in the intrinsic viscosity was observed under the experimental conditions. However, some functionalization of the chain ends may be possible at a high concentration of the epoxy. ECY was more reactive, and the molecular weight of the processed PET increased, although the value of the commercial untreated polyester was not attained. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1995–2003, 2003
Evaluation of a novel method to estimate absolute bioavailability of drugs from oral data
Authors: Hinderling Peter H.
Published: January 2003

The goal of this investigation was to evaluate the performance of a novel method allowing estimation of absolute bioavailability from oral data only. In contrast to the traditional method, which compares areas under the drug concentration time curves after oral and intravenous administration in subjects with normal renal function, the novel method uses total and renal clearance values following oral administration from subjects with varying renal functions to estimate bioavailability. The novel method can also provide estimates for nonrenal clearance.

Published data on total clearance and renal clearance of drugs obtained from subjects with variable renal functions were collected, the novel method applied, estimates of bioavailability and nonrenal clearance obtained and compared with reported estimates by the traditional methods. In addition computations were performed to assess various factors that could possibly affect the reliability of the novel method.

The results indicated that the novel method provides accurate estimates for bioavailability of drugs meeting the prerequisites: linear kinetics, predominant renal excretion in normals, absence of metabolic polymorphism and independence of bioavailability and nonrenal clearance from renal function. The average (standard deviation) of the prediction error and bias of the bioavailability estimates by the novel method was 7.8 (6.0) and −1.4 (9.8)%, respectively. The estimates for nonrenal clearance by the novel method were less accurate. The computations confirmed that the estimates by the novel method are sensitive to renal‐function dependent changes in nonrenal clearance and bioavailability and also depend on the extent of renal excretion of a drug.

In conclusion, the novel method's main use is to diagnose absence or presence of changes in bioavailability and non‐renal clearance of drugs in populations with varying renal function. Copyright © 2002 John Wiley & Sons, Ltd.
Plasma concentration profiles of ketamine and norketamine after administration of various ketamine preparations to healthy Japanese volunteers
Authors: Yanagihara Yoshitsugu , Ohtani Michiteru , Kariya Satoru , Uchino Katsuyoshi , Hiraishi Teiko , Ashizawa Naofumi , Aoyama Takao , Yamamura Yoshikazu , Yamada Yasuhiko , Iga Tatsuji
Published: January 2003

Ketamine is known to provide analgesic effects without an anesthetic when administered in a low dose. We previously reported that a tablet containing ketamine had analgesic effects in patients with neuropathic pain. In the present study, we compared the plasma concentration profiles of the enantiomers of ketamine and its active metabolite, norketamine, up to 8 h after the administration of 20 mg of ketamine by injection, after the administration of two tablets containing 25 mg of ketamine, after the administration of two sublingual tablets containing 25 mg of ketamine, after the insertion of a suppository containing 50 mg of ketamine, and after the application of a nasal spray containing 25 mg of ketamine to three healthy volunteers. The plasma concentration of ketamine biexponentially declined after the administration by injection; the value of T1/2β for ketamine was approximately 120 min. The bioavailability of the tablet was estimated to be approximately 20%; the area under the plasma concentration–time curve, (AUC)0→8 h, of norketamine was approximately 500 ng h/ml in both enantiomers. The bioavailabilities of the sublingual tablet and the suppository were estimated to both be approximately 30%; the AUC0→8 h of norketamine was 280–460 ng h/ml in both enantiomers. The plasma concentration profiles of the sublingual tablet and the suppository were almost similar to that of the tablet. The bioavailability of the nasal spray was estimated to be approximately 45%, which was the highest value among the preparations tested, and the AUC0→6 h of norketamine was low (approximately 100 ng h/ml) in both enantiomers. These pharmacokinetic findings suggested that all of the ketamine preparations tested in this study may be useful for the alleviation of neuropathic pain. We propose that the type of ketamine preparation should be selected in accordance with the patient's disease condition and the required dosage amount of ketamine. Copyright © 2002 John Wiley & Sons, Ltd.
Characteristics of the gastric pH profiles of unfed and fed cynomolgus monkeys as pharmaceutical product development subjects
Authors: Kondo Hiromu , Shinoda Tatsuki , Nakashima Hiroshi , Watanabe Takashi , Yokohama Shigeharu
Published: January 2003

Gastric pH is an important factor which significantly affects the dissolution of drugs, and therefore their bioavailability. In this study, the gastric pHs were measured directly with a miniature pH electrode inserted through the nostril into the body of the stomach of cynomolgus monkeys. Results from three separate sets of measurements using the same male monkeys indicated that the median gastric pH profiles of unfed monkeys were low, fluctuating between pH 1 and pH 3. However, the median gastric pHs in fed monkeys given about 108 g of a biscuit‐type solid food, which are commonly provided, shifted toward a more neutral range between pH 5 and pH 7, and remained in this range for about 9 h. This result contrasted with reported results for humans after eating a standard meal, which showed a neutral range between pH 5 and pH 7 for a brief period. Consequently, these results indicate that although the gastric pH of unfed cynomolgus monkeys is similar to that of fasting humans, there is a great difference in the gastric pH profiles between humans and monkeys after eating, which suggests that further studies are needed to establish optimal feeding conditions for bioavailability studies in monkeys. Copyright © 2002 John Wiley & Sons, Ltd.
Chiral separation of 2,3‐allenoic acid by capillary zone electrophoresis using cyclodextrin derivatives
Authors: Xu Xu , Bao Xiao‐Ling , Dong Xiao‐Wei , Shi Zhang‐Jie , Yu Zhan‐Qian , Ma Sheng‐Ming
Published: January 2003

In this paper, five of six samples of 2,3‐allenoic acid enantiomers were separated by capillary zone electrophoresis (CZE) using hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) and hydroxypropyl‐γ‐cyclodextrin (HP‐γ‐CD) as chiral selectors. Using HP‐β‐CD for chiral separation, three of the six enantiomers were separated. Five experimental conditions including HP‐β‐CD concentration, pH, buffer concentration, temperature, and running voltage were investigated for their influence on separation and migration using enantiomers of 2‐methyl‐4‐phenyl‐2,3‐butadienoic acid (A) and 2‐(n‐propyl)‐4‐phenyl‐2,3‐butadienoic acid (B) as samples. Good separation results were observed when [HP‐β‐CD] = 3–12 mmol/L and pH = 7–9 for samples A and B. The temperature range of 15–25°C can be selected for convenience. According to the chiral separation results, HP‐β‐CD and HP‐γ‐CD should be valuable selectors to separate 2,3‐allenoic acids and HP‐γ‐CD was suggested to separate the 2,3‐allenoic acid samples with a group at 4‐position bulkier than phenyl. Chirality 15:201–205, 2003. © 2003 Wiley‐Liss, Inc.
Innovations of the NetSolve Grid Computing System
Authors: Arnold Dorian C. , Casanova Henri , Dongarra Jack
Published: January 2003

The NetSolve Grid Computing System was first developed in the mid 1990s to provide users with seamless access to remote computational hardware and software resources. Since then, the system has benefitted from many enhancements like security services, data management faculties and distributed storage infrastructures. This article is meant to provide the reader with details regarding the present state of the project, describing the current architecture of the system, its latest innovations and other systems that make use of the NetSolve infrastructure. Copyright © 2002 John Wiley & Sons, Ltd.
Composition and variability of the essential oil of Sardinian Thymus herba‐barona Loisel
Authors: Usai Marianna , Atzei Aldo , Pintore Giorgio , Casanova Ioseph
Published: January 2003

The essential oils from nine wild populations of the Sardinian Thymus herba‐barona Loisel (Labiatae) were chemically characterized to identify the different chemotypes. GC and GC–MS analysis showed that in Sardinia only two chemotypes (thymol and carvacrol) are present. The carvacrol chemotype is predominant and this compound was found in high concentration (50.7–79.4%) in seven of the nine populations studied. The thymol chemotype was found in only two populations (34.2–56.2%). Analyses also showed that the other main components of the oils of T. herba‐barona, were 3‐heptanone (1.4–5.6%), 3‐octanone (1.4–5.5%) and borneol (2.5–8.3%). p‐Cymene is present at 1.2–5.6% but is not present in plants from the Tonara medium station, where O‐cymene (1.9%) is present instead. Copyright © 2002 John Wiley & Sons, Ltd.
Composition of the essential oils from leaves of two Hedyosmum spp. from Bolivia
Authors: Lorenzo Daniel , Loayza Ingrid , Dellacassa Eduardo
Published: January 2003

Essential oils obtained by hydrodistillation from aerial parts of Hedyosmum angustifolium (Ruiz & Pavón) Solms‐Laubach and H. scabrum (Ruiz & Pavón) Solms‐Laubach from Bolivia were analysed by GC–FID and GC–MS. Monoterpene hydrocarbons, especially α‐ and β‐pinene, and oxygen containing monoterpenes, mainly 1,8‐cineole and linalool, were the major constituents found in the oils of H. angustifolium. The oil of H. scabrum was mainly made up of monoterpenes, in particular δ‐3‐carene, the sesquiterpene hydrocarbons α‐gurjunene and germacrene D, and 3′, 4′‐dimethoxypropiophenone. For both oils, the enantiomeric distribution of α‐pinene, sabinene, β‐pinene, limonene, linalool, terpinen‐4‐ol and α‐terpineol was studied by multidimensional HRGC–HRGC. The main difference between the oils corresponded to the reverse enantiomeric distribution found for linalool, indicating a clear index of different metabolic response in each species. Copyright © 2002 John Wiley & Sons, Ltd.
Formation of fragrant materials from odourless glycosidically‐bound volatiles on skin microflora (Part 2)
Authors: Ikemoto Takeshi , Mimura Kunio , Kitahara Takeshi
Published: January 2003

We have reported that glycosidically bound volatiles (GBVs), known as a plant fragrance precursor, were metabolized by skin microflora to release their aglycones as fragrant materials through in vitro examination. To confirm the practicality of GBVs for the application of fragrant products, headspace measurements have been made to assess the generation of fragrant materials from the skin or head, on which a solution of several GBVs was applied. GBVs, particularly β‐D‐glucoside, gradually changed to fragrant materials even on the skin and head, and seemed to possess an alternative sustained‐release effect to that of ordinary fragrant materials. Copyright © 2002 John Wiley & Sons, Ltd.
A third‐generation matrix metalloproteinase (MMP) inhibitor (ONO‐4817) combined with docetaxel suppresses progression of lung micrometastasis of MMP‐expressing tumor cells in nude mice
Authors: Yamamoto Akihiko , Yano Seiji , Shiraga Minoru , Ogawa Hirohisa , Goto Hisatsugu , Miki Toyokazu , Zhang Helong , Sone Saburo
Published: January 2003

The lung is the common target organ of hematogenous metastasis that restricts the prognosis of cancer patients. MMPs play a pivotal role in metastasis by promoting tumor invasion and angiogenesis; therefore, a large number of MMPIs have been developed. Our purpose was to determine the therapeutic efficacy of a selective‐spectrum MMPI, ONO‐4817 (inhibits MMP‐2 and MMP‐9 but not MMP‐1), against established lung micrometastasis in combination with a cytotoxic anticancer drug, DOC, in a nude mouse model. Human non‐small cell lung cancer PC14PE6 (adenocarcinoma) or H226 (squamous cell carcinoma) cells, expressing MMP‐2, MMP‐9 and/or MMP‐1, were injected i.v. into nude mice on day 0. Mice received a single injection of DOC on day 7 (after establishment of micrometastasis) and/or ONO‐4817 mixed with food from day 7 to the end of experiments. Monotherapy with ONO‐4817 or DOC inhibited formation of lung metastasis by PC14PE6 and H226 cells. In addition, combined use of ONO‐4817 with DOC significantly suppressed the tumor burden of H226 and PC14PE6 cells in the lung and prolonged the survival of PC14PE6‐bearing mice compared to ONO‐4817 or DOC alone. These therapies did not affect the body weight or food intake of tumor‐bearing mice. FIZ revealed that lung lesions, but not nontumor parenchyma of the lung, expressed gelatinolytic activity and that treatment with ONO‐4817 abrogated the gelatinolytic activity in lung lesions. These results suggest that the combined use of MMPIs with cytotoxic anticancer drugs may be helpful in the control of established lung micrometastasis by tumor cells expressing MMPs. © 2002 Wiley‐Liss, Inc.
Prevalence of specific types of human papillomavirus and cervical squamous intraepithelial lesions in consecutive, previously unscreened, West‐African women over 35 years of age
Authors: Xi Long Fu , Touré Papa , Critchlow Cathy W. , Hawes Stephen E. , Dembele Birama , Sow Papa Salif , Kiviat Nancy B.
Published: January 2003

Previous studies among women worldwide have demonstrated that infection with specific types of human papillomaviruses (HPV) is central to the pathogenesis of cervical neoplasia. There is little data, however, concerning the prevalence of specific HPV types and the association of each type with cervical neoplasia among women in sub‐Saharan Africa, who remain at very high risk of cervical cancer. We studied 2,065 consecutive patients aged 35 years or older, presenting to community health clinics in Dakar and Pikine, West Africa, who had not been screened previously for cytologic abnormalities or HPV. Cytologic diagnosis and HPV detection were accomplished using a ThinPrep Pap and a polymerase chain reaction‐based reverse‐line strip assay, respectively. Odds ratios (OR) and associated 95% confidence intervals (CI) were estimated using polynomial logistic regression. Cytologic abnormalities were found in 426 women (20%), including 254 (12%) with atypical squamous cells of undetermined significance, 86 (4%) with low‐grade squamous intraepithelial lesions, 66 (3%) with high‐grade squamous intraepithelial lesions (HSIL) and 20 (1%) with invasive cancer. HPV infection was detected in 18%. Among women with negative cytologic findings, the prevalence of high risk but not low risk HPV types increased with age. HPV16 (2.4%) and HPV58 (1.6%) were the most frequently detected HPV types in this population, as well as being the most strongly associated with risk of HSIL/cancer (HPV16: OR = 88, 95% CI = 39–200; HPV58: OR = 51, 95% CI = 16–161). These data suggest that in addition to HPV16, HPV58 should be considered in the strategic planning of vaccination against cervical cancer in this geographic region. © 2002 Wiley‐Liss, Inc.
Suppression of insulin‐induced AP‐1 transactivation by menin accompanies inhibition of c‐Fos induction
Authors: Yumita Wataru , Ikeo Yasuto , Yamauchi Keishi , Sakurai Akihiro , Hashizume Kiyoshi
Published: January 2003

The translation product of the MEN1 gene, menin, has been reported to suppress JunD‐mediated activator protein‐1 (AP‐1) transactivation and inhibit Ras‐mediated tumor formation, but its molecular mechanisms and physiologic significance have been poorly elucidated. To better understand the function of menin as a tumor suppressor, we examined the effect of menin on physiologically induced AP‐1 activity. Overexpression of menin strongly suppressed insulin‐induced AP‐1 activity in CHO‐IR cells, which express high levels of insulin receptor. We found that menin suppressed c‐Fos induction at the transcriptional level, although that cannot explain the entire mechanism of AP‐1 suppression by menin. Menin did not alter the expression levels of AP‐1 proteins except c‐Fos, phosphorylation of c‐Jun and JunD and DNA binding properties of AP‐1 proteins. Suppression of AP‐1 activation by menin may be exerted through 2 independent mechanisms, direct inhibition on AP‐1‐mediated transcription and suppression of c‐Fos induction. The molecular mechanism of inhibition of AP‐1 function by menin needs further elucidation. © 2002 Wiley‐Liss, Inc.
The patched polymorphism Pro1315Leu (C3944T) may modulate the association between use of oral contraceptives and breast cancer risk
Authors: Chang‐Claude Jenny , Dunning Alison , Schnitzbauer Udo , Galmbacher Petra , Tee Louise , Wjst Matthias , Chalmers Jennifer , Zemzoum Iris , Harbeck Nadia , Pharoah Paul D. P. , Hahn Heidi
Published: January 2003

The gene coding for the human homologue of the Drosophila segment polarity gene patched (PTCH1) is mutated in several common human tumors. In mice, haplodeficiency at the Ptch1 locus results in severe histologic defects in mammary ductal structure. We found no mutations within the coding region of PTCH1 in 17 human primary breast carcinomas. However, the biallelic Pro1315Leu (C3944T) polymorphism of PTCH1 was significantly associated with breast cancer in 41 Bavarian patients compared to 85 healthy controls. We investigated whether this variant influences susceptibility for breast cancer in 611 breast cancer patients diagnosed by age 50 years and 1,057 controls matched by age and study region in Germany and in 1,093 breast cancer patients from the United Kingdom. Allele and genotype frequencies were not different between cases and controls. However, multivariate logistic regression analysis revealed an effect modification of oral contraceptive use (OC) on breast cancer risk by Leu‐carrier status. Compared to women who have Pro/Pro and never used OC, Pro/Pro OC users had an increased odds ratio for breast cancer of 1.7. The odds ratio was also 1.7 for Leu‐carriers who never used OC, but this was attenuated among Leu‐carriers who ever used OC by 20%. The gene‐environmental interaction was confirmed in case‐only analysis of the German and British studies, yielding an interaction odds ratio of 0.7 for premenopausal women (p = 0.06). Longer duration of pill use was associated with a significantly greater risk reduction (p for trend = 0.015). Our novel observation of a differential effect of OC use on breast cancer risk by PTCH1 1315Leu‐carrier status suggests the interesting possibility of the Sonic hedgehog/Patched (SHH/PTCH1) signaling pathway being involved in hormone‐induced development of breast carcinoma. © 2002 Wiley‐Liss, Inc.
Use of stereolithography to manufacture critical‐sized 3D biodegradable scaffolds for bone ingrowth
Authors: Cooke Malcolm N. , Fisher John P. , Dean David , Rimnac Clare , Mikos Antonios G.
Published: January 2003

A novel approach to the manufacture of biodegradable polymeric scaffolds for tissue‐engineering utilizing stereolithography (SLA) is presented. SLA is a three‐dimensional (3D) printing method that uses an ultraviolet laser to photo‐crosslink a liquid polymer substrate. The current generation of SLA devices provide a 3D printing resolution of 0.1 mm. The experiments utilized a biodegradable resin mixture of diethyl fumarate (DEF), poly(propylene fumarate) (PPF), and a photoinitiator, bisacylphosphine oxide (BAPO). The PPF is crosslinked with the use of the SLA's UV laser (325‐nm wavelength). An SLA device was retrofitted with a custom fixture build tank enclosing an elevator‐driven build table. A 3D prototype model testing the manufacturing control this device provides was created in a computer‐aided‐design package. The resulting geometric data were used to drive the SLA process, and a DEF/PPF prototype part was successfully manufactured. These scaffolds have application in the tissue engineering of bony substrates. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 64B: 65–69, 2002
Effects of multipurpose solutions (MPS) for hydrogel contact lenses on gap‐junctional intercellular communication (GJIC) in rabbit corneal keratocytes
Authors: Sumide Taizo , Tsuchiya Toshie
Published: January 2003

To ensure the effects of multipurpose solutions (MPS) for hydrogel contact lenses on the cornea, the inhibitory activity of three types of MPS on corneal cells has been evaluated with the use of scrape loading and dye transfer assay (SLDT assay) and Western blotting on rabbit corneal keratocytes (RC4). In SLDT assay, MPS‐A and poloxamine showed dose‐dependent inhibitory activity, suggesting the inhibitory action of MPS‐A and poloxamine to gap junctional intercellular communication (GJIC) in the tested cells. Moreover, after treatment with MPS‐A, the GJIC was initially inhibited within 4 h, and thereafter gradually turned to an approximately 60% level of the initial value. When MPS‐A was removed from the incubation media after exposure of the cells, the recovery of GJIC was time dependent and returned to approximately initial levels at 8 h. Complete recovery was established after approximately 24 h. These findings suggested that the inhibitory action of MPS‐A on corneal keratocytes was reversible. This inhibition was accompanied by a decrease in the quantity of connexin‐43, which is a major protein constituting the gap junctional channel of these cells, and its change in the phosphorylation state. Taken together, it was suggested that MPS‐A interacts with connexin‐43, inducing an inhibitory action on GJIC. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 64B: 57–64, 2003
Antibiotic bone cement for the treatment of pseudomonas aeruginosa in joint arthroplasty: Comparison of tobramycin and gentamicin‐loaded cements
Authors: Scott Christopher P. , Higham Paul A.
Published: January 2003

One hundred clinical isolates of Pseudomonas aeruginosa were collected from 22 medical centers throughout Europe and were challenged with two aminoglycoside‐loaded bone cements, employing a modified in vitro Kirby–Bauer susceptibility model. The results of this study show that Simplex® P with tobramycin exhibits antibacterial activity against 98% of the strains tested, compared to 93% for Palacos with gentamicin. Additionally, for strains that were susceptible to the antibiotic bone cement formulations, the average zone of inhibition produced around the tobramycin‐loaded cement disks was approximately 25% greater than that seen around the gentamicin‐loaded cement disks. This difference was statistically significant (p ≪ 0.01). Tobramycin‐loaded bone cement is therefore the preferred formulation when addressing Pseudomonas aeruginosa in septic joint arthroplasty. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 64B: 94–98, 2003
Mechanisms of intestinal calcium absorption
Authors: Bronner Felix
Published: January 2003

Calcium is absorbed in the mammalian small intestine by two general mechanisms: a transcellular active transport process, located largely in the duodenum and upper jejunum; and a paracellular, passive process that functions throughout the length of the intestine. The transcellular process involves three major steps: entry across the brush border, mediated by a molecular structure termed CaT1, intracellular diffusion, mediated largely by the cytosolic calcium‐binding protein (calbindinD9k or CaBP); and extrusion, mediated largely by the CaATPase. Chyme travels down the intestinal lumen in ∼3 h, spending only minutes in the duodenum, but over 2 h in the distal half of the small intestine. When calcium intake is low, transcellular calcium transport accounts for a substantial fraction of the absorbed calcium. When calcium intake is high, transcellular transport accounts for only a minor portion of the absorbed calcium, because of the short sojourn time and because CaT1 and CaBP, both rate‐limiting, are downregulated when calcium intake is high. Biosynthesis of CaBP is fully and CaT1 function is approximately 90% vitamin D‐dependent. At high calcium intakes CaT1 and CaBP are downregulated because 1,25(OH)2D3, the active vitamin D metabolite, is downregulated. J. Cell. Biochem. 88: 387–393, 2003. © 2002 Wiley‐Liss, Inc.
Effects of 1α,25(OH)2D3 and its analogs on dendritic cell function
Authors: Griffin Matthew D. , Kumar Rajiv
Published: January 2003

1α,25‐Dihydroxyvitamin D3 (1α,25(OH)2D3) and non‐calcemic vitamin D analogs induce a persistent state of immaturity in dendritic cells both in vitro and in vivo. These effects are transcriptional in nature, involve alterations in surface ligands as well as cytokine synthesis and release, and are dependent upon the presence of the vitamin D receptor. The vitamin D endocrine system could also play a role in altering immune function in normal physiological conditions. Distinct differences exist in lymph node dendritic cells of vitamin D receptor null mutant mice when compared to normal mice. J. Cell. Biochem. 88: 323–326, 2003. © 2002 Wiley‐Liss, Inc.
Expression, structure‐function, and molecular modeling of vitamin D P450s
Authors: Omdahl J.L. , Bobrovnikova E.V. , Annalora A. , Chen P. , Serda R.
Published: January 2003

Although vitamin D3 is a natural product of a sunlight‐mediated process in the skin, the secosteroid's biological function is dependent upon specific cytochrome P450 enzymes that mediate the parent vitamin's bioactivation and inactivation. Cytochrome P450C1 (CYP27B1) is the regulatory rate‐limiting enzyme that directs the bioactivation process through introduction of a C‐1α hydroxyl group. The resultant 1,25‐dihydroxyvitamin D3 (1,25D) is the biologically active secosteroid hormone that directs the multitude of vitamin D‐dependent actions involved with calcium homeostasis, cellular differentiation and growth, and the immune response. The circulating and cellular level of 1,25D is regulated through a coordinated process involving the hormone's synthesis and degradation. Central to the degradation and turnover of 1,25D is the regulatory multi‐catalytic cytochrome P450C24 (CYP24) enzyme that directs the introduction of C‐24R groups onto targeted 25‐hydroxy substrates. Discussed in this article is the action of the rat CYP24 to catalyze the side‐chain oxidation and cleavage of 25‐hydroxylated vitamin D metabolites. Expression and characterization of purified recombinant rat CYP24 is discussed in light of mutations directed at the enzyme's active site. J. Cell. Biochem. 88: 356–362, 2003. © 2002 Wiley‐Liss, Inc.
Dwarf male of symbion pandora (cycliophora)
Authors: Obst Matthias , Funch Peter
Published: January 2003

This study clarifies the identity and development of the male in the life cycle of Symbion pandora. The male is not produced directly by the feeding stage, as previously thought, but arises as a distinct individual from budding cells inside an intermediate stage named the Prometheus larva. The morphology and the development of the two distinct stages are described with light and electron microscopy. Furthermore, the following terminology is suggested to clearly distinguish between the different individuals: 1) the Prometheus larva, which is the free‐swimming individual being produced inside the feeding stage; 2) the attached Prometheus larva on the feeding stage, which mostly degenerates following settlement, except for the internal budding cells; and 3) the dwarf male, which is the ciliated, sexually mature stage. The budding cells inside the attached Prometheus larva usually develop two internal dwarf males. Each dwarf male is heavily ciliated and has a well‐developed nervous system with a relatively large brain, numerous gland and muscle cells, testis with bundles of sperm, and one penial structure. The male lacks a gut, as in the other free stages in the life cycle of Symbion pandora. This study also indicates that the dwarf male is freed from the attached Prometheus larva. Copulation, which has not been observed yet, probably takes place between a free‐swimming male and the female, either while the female is released or afterwards. J. Morphol. 255:261–278, 2003. © 2003 Wiley‐Liss, Inc.