bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunotherapy with dendritic cells and CpG oligonucleotides can be combined with chemotherapy without loss of efficacy in a mouse model of colon cancer
Authors: Bourquin Carole , Schreiber Susanne , Beck Sebastian , Hartmann Gunther , Endres Stefan
Published: December 2005

Although immunotherapy has shown promising results in the treatment of cancer, clinical studies assessing immunologic approaches in patients with advanced cancer will seldom be conducted in the absence of conventional treatment strategies such as chemotherapy. Here we investigate the combination of chemotherapy with CpG oligonucleotide and dendritic cell‐based immunotherapy in the C26 mouse model of colon carcinoma. The coinjection of antigen‐pulsed, mature dendritic cells and CpG oligonucleotides together with a peritumoral injection of CpG oligonucleotides elicits a CD8 T‐cell response resulting in tumor rejection and long‐term protection in the C26 model. Tumor‐bearing mice were treated weekly for 4 weeks by this immunotherapy protocol, by 5‐fluorouracil plus leucovorin or irinotecan, or by the combination of immunotherapy and chemotherapy. We observed that immunotherapy was more effective in reducing tumor growth and increasing survival than 5‐fluorouracil or irinotecan. Immunotherapy was well tolerated, whereas therapeutic doses of 5‐fluorouracil or irinotecan were associated with dose‐limiting toxicity. Furthermore, the efficacy of immunotherapy combined with either 5‐fluorouracil or irinotecan was similar to that of immunotherapy alone. Addition of immunotherapy to either 5‐fluorouracil or irinotecan treatment strongly decreased the toxicity of chemotherapy. Immunotherapy both with and without chemotherapy generated a memory immune response, leading to tumor rejection in mice rechallenged with C26 tumor cells up to several months after treatment. In summary, immunotherapy with a combination of dendritic cells and CpG oligonucleotides is superior to chemotherapy in the C26 tumor model. This immunotherapy protocol can be combined with current chemotherapy agents with no loss in therapeutic activity. © 2005 Wiley‐Liss, Inc.
On partitions of the q‐ary Hamming space into few spheres
Authors: Klein Andreas , Wessler Markus
Published: December 2005

In this paper, we present a generalization of a result due to Hollmann, Körner, and Litsyn [9]. They prove that each partition of the n‐dimensional binary Hamming space into spheres consists of either one or two or at least n + 2 spheres. We prove a q‐ary version of that gap theorem and consider the problem of the next gaps. © 2005 Wiley Periodicals, Inc. J Combin Designs 14: 183–201, 2006
The existence spectrum of golf designs
Authors: Chang Yanxun
Published: December 2005

In this note, a golf design of order 41 is constructed. Combined Colbourn and Nonay's result, the existence spectrum of golf design of order υ is the set {υ: υ≡1 (mod 2), υ ≥ 3, υ ≠ 5}. © 2005 Wiley Periodicals, Inc. J Combin Designs 15: 84–89, 2007
The relative contribution of posttraumatic and acculturative stress to subjective mental health among Bosnian refugees
Authors: Knipscheer Jeroen W. , Kleber Rolf J.
Published: December 2005

The relationship between posttraumatic stress reactions, cultural adaptation, and mental health symptoms is still poorly understood. This empirical study examined the relative contribution of both posttraumatic reactions and acculturation rates to subjective mental health in 2 groups of Bosnian refugees, a clinical group (N = 34) and a nonclinical community group (N = 44). As hypothesized, posttraumatic reactions were highly predictive of mental health state in both groups. In addition, two specific acculturation aspects, cultural affiliation and the obtaining of instrumental skills, were significantly related to mental health symptoms. The implications of these findings for mental health professionals working with refugees and other traumatized populations are considered. © 2005 Wiley Periodicals, Inc. J Clin Psychol 62: 339–353, 2006.
Matchings in hypergraphs of large minimum degree
Authors: Kühn Daniela , Osthus Deryk
Published: December 2005

It is well known that every bipartite graph with vertex classes of size n whose minimum degree is at least n/2 contains a perfect matching. We prove an analog of this result for hypergraphs. We also prove several related results that guarantee the existence of almost perfect matchings in r‐uniform hypergraphs of large minimum degree. Our bounds on the minimum degree are essentially best possible. © 2005 Wiley Periodicals, Inc. J Graph Theory 51: 269–280, 2006
Numbers of edges in supermagic graphs
Authors: Drajnová Svetlana , Ivančo Jaroslav , Semaničová Andrea
Published: December 2005

A graph is called supermagic if it admits a labelling of the edges by pairwise different consecutive integers such that the sum of the labels of the edges incident with a vertex is independent of the particular vertex. In the paper we establish some bounds for the number of edges in supermagic graphs. © 2005 Wiley Periodicals, Inc. J Graph Theory 52: 15–26, 2006
Kinetic study of site directed and randomly immobilized his‐tag alkaline phosphatase by flow injection chemiluminescence
Authors: Zhang Juankun , Cass Anthony E. G.
Published: December 2005

We immobilized his‐tag alkaline phosphatase (ALP) randomly and with the desirable orientation (site directed) to compare the effects of the enzyme activity on the beads. The chemiluminescence was employed to increase the sensitivity of enzyme labelled assays. Flow injection was also carried out for the detection of chemical and biological molecules in flow solutions. The Vmax of randomly immobilized his‐tag ALP was 1.2 and the Vmax of site directed immobilized his‐tag ALP was 1.5. In other words, the activity of site directed immobilized his‐tag ALP was about 1.3‐folds increased. The detection limit was detected to be 6×10−6 M for the flow injection system. Copyright © 2006 John Wiley & Sons, Ltd.
Adult‐onset deficiency in growth hormone and insulin‐like growth factor‐I decreases survival of dentate granule neurons: Insights into the regulation of adult hippocampal neurogenesis
Authors: Lichtenwalner Robin J. , Forbes M. Elizabeth , Sonntag William E. , Riddle David R.
Published: December 2005

Insulin‐like growth factor‐I (IGF‐I), long thought to provide critical trophic support during development, also has emerged as a candidate for regulating ongoing neuronal production in adulthood. Whether and how IGF‐I influences each phase of neurogenesis, however, remains unclear. In the current study, we used a selective model of growth hormone (GH) and plasma IGF‐I deficiency to evaluate the role of GH and IGF‐I in regulating cell proliferation, survival, and neuronal differentiation in the adult dentate gyrus. GH/IGF‐I‐deficient dwarf rats of the Lewis strain were made GH/IGF‐I replete throughout development via twice daily injections of GH, and then GH/IGF‐I deficiency was initiated in adulthood by removing animals from GH treatment. Bromodeoxyuridine (BrdU) labeling revealed no effect of GH/IGF‐I deficiency on cell proliferation, but adult‐onset depletion of GH and plasma IGF‐I significantly reduced the survival of newly generated cells in the dentate gyrus. Colabeling for BrdU and markers of immature and mature neurons revealed a selective effect of GH/IGF‐I deficiency on the survival of more mature new neurons. The number of BrdU‐labeled cells expressing the immature neuronal marker TUC‐4 did not differ between GH/IGF‐I‐deficient and ‐replete animals, but the number expressing only the marker of maturity NeuN was lower in depleted animals. Taken together, results from the present study suggest that, under conditions of short‐term GH/IGF‐I deficiency during adulthood, dentate granule cells continue to be produced, to commit to a neuronal fate, and to begin the process of neuronal maturation, whereas survival of the new neurons is impaired. © 2005 Wiley‐Liss, Inc.
Cadmium‐induced astroglial death proceeds via glutathione depletion
Authors: Im Joo‐Young , Paik Sang‐Gi , Han Pyung‐Lim
Published: December 2005

Cadmium is a heavy metal that accumulates in the body, and its accumulation in the brain damages both neurons and glial cells. In the current study, we explored the mechanism underlying cadmium toxicity in primary cortical astroglia cultures. Chronic treatment with 10 μM cadmium was sufficient to cause 90% cell death in 18 hr. However, unlike that observed in neurons, cadmium‐induced astroglial toxicity was not attenuated by the antioxidants trolox (100 μM), caffeic acid (1 mM), and vitamin C (1 mM). In contrast, extracellular 100 μM glutathione (GSH; γ‐Glu‐Cys‐Gly) or 100 μM cysteine almost completely blocked cadmium‐induced astroglial death, whereas 300 μM oxidized GSH (GSSG) or 300 μM cystine, which do not have the free thiol group, were ineffective. In addition, cadmium toxicity was noticeably inhibited or enhanced when intracellular GSH was, respectively, increased by using the cell‐permeable glutathione ethyl ester (GSH‐EE) or depleted by using buthionine sulfoximine (BSO), an inhibitor of γ‐glutamylcysteine synthetase. In agreement with these data, intracellular GSH levels were found to be depressed in cadmium‐treated astrocytes. These results suggest that the toxic effect of cadmium on primary astroglial cells involves GSH depletion and, furthermore, that GSH administration can potentially be used to counteract cadmium‐induced astroglial cell death therapeutically. © 2005 Wiley‐Liss, Inc.
Minocycline attenuates white matter damage in a rat model of chronic cerebral hypoperfusion
Authors: Cho Kyung‐Ok , La Hyen O. , Cho Young‐Jin , Sung Ki‐Wug , Kim Seong Y.
Published: December 2005

White matter lesions are thought to result from chronic cerebral ischemia and constitute a core pathology of subcortical vascular dementia. This rarefaction has been known to be associated with microglial activation. We investigated whether minocycline, a microglial inhibitor, attenuates the white matter damage induced by chronic cerebral hypoperfusion that is used as a model of vascular dementia. Male Wistar rats were subjected to bilateral, permanent occlusion of the common carotid arteries (BCCAO) to induce chronic cerebral hypoperfusion. Minocycline or saline was injected daily for 2 weeks after BCCAO. In the corpus callosum and the optic tract, white matter damage observed with Klüver‐Barrera staining was significantly attenuated in the minocycline‐treated group compared to saline‐treated controls. In control rats, immunoreactivities of major basic protein (MBP), Ox‐42 as a microglial marker, and matrix metalloproteinase (MMP)‐2 were increased in the corpus callosum. Minocycline significantly reduced these changes. Co‐expression of Ox‐42 and MMP‐2 was confirmed by double immunofluorescence histochemistry. Our results suggest that chronic treatment with minocycline could be protective against at least some ischemic white matter damage, and its mechanism may be related to suppressing microglial activation. © 2005 Wiley‐Liss, Inc.
Protein glutathionylation in human central nervous system: Potential role in redox regulation of neuronal defense against free radicals
Authors: Sparaco Marco , Gaeta Laura Maria , Tozzi Giulia , Bertini Enrico , Pastore Anna , Simonati Alessandro , Santorelli Filippo Maria , Piemonte Fiorella
Published: December 2005

Neuronal defense against free radicals is mediated primarily by the glutathione system. A cerebral defect of this system gives rise to the oxidative stress occurring in some neurological diseases. Glutathione provides a means of regulating protein function by glutathionylation, consisting of the formation of mixed disulfides between cysteines and glutathione. The glutathionylation of proteins, during both constitutive metabolism and oxidative stress, represents for the cell a mechanism to link physiological processes, and/or adaptive stress responses, to changes in intracellular redox states. In this study, we analyzed the topographic distribution of the protein glutathionylation normally occurring in human central nervous system. Constitutively glutathionylated proteins appeared uniformly distributed throughout all cortical layers of the cerebral and cerebellar cortex as well as throughout the gray matter of the spinal cord. The degree of immunocytochemical staining was clear in neurons, mild in oligodendrocytes, and weaker in astrocytes. The proteins preferentially glutathionylated were cytoskeletal proteins. Our results suggest a potential role of glutathionylation in the redox regulation of neuronal survival and in the control of axon/dendrite stability. © 2005 Wiley‐Liss, Inc.
Behavioral motor recovery in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐lesioned squirrel monkey (Saimiri sciureus): Changes in striatal dopamine and expression of tyrosine hydroxylase and dopamine transporter proteins
Authors: Petzinger Giselle M. , Fisher Beth , Hogg Elizabeth , Abernathy Avery , Arevalo Pablo , Nixon Kerry , Jakowec Michael W.
Published: December 2005

The neurotoxicant 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) provides an excellent opportunity to study repair and response to injury in the basal ganglia. Administration to mammals leads to the destruction of nigrostriatal dopaminergic neurons and depletion of striatal dopamine. In the squirrel monkey (Saimiri sciureus), MPTP‐lesioning results in parkinsonian motor symptoms including bradykinesia, postural instability, and rigidity. Over time animals display motor behavioral recovery. To better understand this mechanism we employed a lesioning regimen of two or six subcutaneous injections of MPTP (2.0 mg/kg, free‐base) to generate mild or moderate parkinsonism. Brain tissue was harvested at 6 weeks or 9 months after the last injection and analyzed for dopamine and its metabolites by high performance liquid chromatography (HPLC), and by immunohistochemical staining and Western immunoblotting for the expression of tyrosine hydroxylase (TH), dopamine transporter (DAT), and dopamine‐ and cAMP‐responsive protein phosphatase of 32 kDa (DARPP‐32), an effector molecule enriched in striatal medium spiny neurons. Several months after MPTP‐lesioning, when squirrel monkeys displayed full motor behavioral recovery, striatal dopamine levels remained low with a greater return in the ventral striatum. This finding is consistent with other reports using neurotoxicant‐lesioning models of the basal ganglia in rodents and other species of nonhuman primates. Elevated dopamine turnover ratio and decreased DAT expression appeared in early behavioral recovery at the 6‐week time point in both mild‐ and moderate‐parkinsonian monkeys. Tyrosine hydroxylase and DAT expression was increased in late stage recovery even within dopamine‐depleted regions and supports sprouting. Altered DARPP‐32 expression suggests a role of medium spiny neurons in recovery. © 2005 Wiley‐Liss, Inc.
Modulation of excitability as an early change leading to structural adaptation in the motor cortex
Authors: Manto Mario , Oulad ben Taib Nordeyn , Luft Andreas R.
Published: December 2005

The excitability of the motor cortex is a function of single cell excitability, synaptic strength, and the balance between excitatory cells and inhibitory cells. Sustained periods of sensory stimulation enhance the excitability in the motor cortex. This adaptation, which represents an early change in cortical network function effective in motor learning and recovery from a motor deficit, is followed by longer‐lasting changes, such as modifications in cortical somatotopy, and by structural plasticity. Interventions aiming at increasing excitability also positively affect learning processes. Recent studies highlight that the cerebellum, especially the interpositus nucleus, plays a key function in the adaptation of the motor cortex to repeated trains of peripheral stimulation. Interpositus neurons, which receive inputs from the sensorimotor cortex and the spinal cord, are involved in somesthetic reflex behaviors and assist the cerebral cortex in transforming sensory signals to motor‐oriented commands by acting via the cerebello‐thalamo‐cortical projections. Moreover, climbing fibers originating in the inferior olivary complex and innervating the nucleus interpositus mediate highly integrated sensorimotor information derived from spinal modules. The intermediate cerebellum allows the motor cortex to tune the gain of polysynaptic responses originating from the spinal cord after repetitive trains of peripheral stimulation, allowing an online calibration of cutaneo‐muscular responses. © 2005 Wiley‐Liss, Inc.
Radiographic classification of osteogenesis during bone distraction
Authors: Li Ru , Saleh Michael , Yang Lang , Coulton Les
Published: December 2005

Successful limb lengthening requires serial radiological evaluation of the progression of healing of the regenerate bone. However, there is no radiographic classification system that shows how the regenerate should progress during treatment in adults. The study aimed to address this need.

A series of radiographs were studied from 92 patients (125 segments) who had undergone bone lengthening. A radiographic classification of osteogenesis was developed based on callus shape and radiographic features that occur between osteotomy and fixator removal.

This classification system used both shape and type of feature to condense and record the radiographic information, but type of feature alone was sufficient to predict outcome. The concurrence and reproducibility of the classification system was tested by inter‐ and intra‐observer studies. The degree of consistent repetition and agreement between observers suggests that the classification system is reliable, reproducible, and therefore should be robust in use.

This classification system provides an insight into osteogenesis; it allows the progress of the bone healing to be assessed against a successful pattern of healing. Hence, potential problems can be predicted and clinical changes made to improve outcome. The classification can be simplified to make it more appropriate for clinical use. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:339–347, 2006
Oscillatory fluid flow regulates glycosaminoglycan production via an intracellular calcium pathway in meniscal cells
Authors: Eifler Robert L. , Blough Eric R. , Dehlin Jennifer M. , Haut Donahue Tammy L.
Published: December 2005

Mechanical loading in the form of oscillatory fluid flow‐induced shear stress was applied to meniscal cells while the biochemical response [intracellular calcium mobilization and sulfated glycosaminoglycan (GAG) production] was studied. Isolated rabbit meniscal cells were cultured onto microscope slides and placed in a parallel plate flow chamber. Cells were exposed to oscillating fluid flow‐induced shear stresses of 4 Pa for sulfated GAG studies and 0–6.5 Pa for calcium studies. The calcium response was monitored using a fluorescent probe and imaging techniques, sulfated GAG production was measured using the modified 1,9‐dimethylmethylene blue method, and thapsigargin was used to block intracellular calcium ([Ca2+]i) mobilization. A significant dose‐dependent relationship was found for the percentage of cells responding to oscillating fluid flow with an increase in [Ca2+]i versus shear stress level. The percentage of cells responding decreased linearly from 72% ± 17% at 6.5 Pa to 28% ± 7% at 2.0 Pa to 2% ± 1% for baseline no‐flow (0 Pa). No differences were found in the amplitude of the calcium response of responding cells for any shear stress level. Oscillating fluid flow‐induced shear stresses of 4 Pa produced a significantly greater amount of sulfated GAGs (253 ± 95 ng GAG/µg cell protein) compared to the no‐flow control (158 ± 86 ng/µg). The addition of thapsigargin to the media inhibited both the intracellular calcium response to oscillating fluid flow (less than 1.5% of the cells responded) and the increase in GAG production following oscillating fluid flow, which was returned to control levels (170 ± 72 ng/µg). These findings suggest that oscillatory fluid flow‐induced shear stress increases intracellular calcium levels and sulfated GAG production. Furthermore, they suggests that calcium may modulate the biochemical pathway that leads to sulfated GAG production. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:375–384, 2006
Chondrocyte injection in distraction epiphysiolysis (rabbit model)
Authors: Ahn Jae I. , Erdin Robert A. , Smith Richard , Canale S. Terry , Hasty Karen A.
Published: December 2005

The purpose of this study was to determine if cultured chondrocytes could prevent premature closure of the physis after physeal distraction in a rabbit model. Epiphyseal distraction at the proximal tibial epiphysis was performed in 24 immature rabbits. Chondrocytes were harvested from the iliac apophysis. The animals were divided into three groups: A, epiphyseal distraction alone; B, injection of phosphate buffered saline (PBS) after epiphyseal distraction; and C, injection of cultured chondrocytes after epiphyseal distraction. After epiphyseal separation was noted radiographically, each animal was evaluated at routine intervals. At 2 to 4 weeks, significant tibial lengthening as compared to the contralateral tibia was noted in all three groups. At 10 weeks, lengthening was apparent only in group C; in groups A and B, the operated tibia was shorter than the unoperated one. Histologic examination at 4 weeks revealed partial bony bridge formation with cell clustering in the fibrocartilaginous matrix in groups A and B. In group C, the matrix showed a typical hyaline aspect with cells organized in columns at the injection site. The zone of hypertrophic chondrocytes was enlarged. It appears that the injected cells differentiated into hypertrophic chondrocytes and delayed premature physeal closure. At 10 weeks after distraction of the physis, the width of the physis was restored to 75% of normal, but disordered chondrocyte growth with cell clustering was present in the cell‐injected group. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:355–365, 2006
Langerhans cell histiocytosis and human herpes virus 6 (HHV‐6), an analysis by real‐time polymerase chain reaction
Authors: Glotzbecker Michael P. , Dormans John P. , Pawel Bruce R. , Wills Brian P. , Joshi Yagnya , Elkan Michael , Hodinka Richard L.
Published: December 2005

Patients with Langerhans cell histiocytosis (LCH) usually present to orthopedic surgeons because this disease most commonly affects bone. The pathogenesis of LCH is unknown, although roles for environmental, infectious, immunologic, and genetic causes have been postulated. More specifically, there is limited data suggesting that human herpes virus 6 (HHV‐6) may be a potential etiologic agent. Frozen biopsy material was obtained from 13 patients with LCH and 20 patients without the disease. After ensuring histologic adequacy of the material, the tissue was tested for HHV‐6 by qualitative and quantitative real‐time TaqMan PCR. Four of 13 patients with LCH had evidence of HHV‐6 DNA in their tissue while 7 of 20 control patients tested positive for HHV‐6 genome. Viral loads are reported for the positive patients; no statistical difference was observed in the presence or quantity of HHV‐6 DNA found in either population, suggesting that the prevalence of HHV‐6 in the tissue of LCH patients is the same as that found in tissue from individuals without disease. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:313–320, 2006
T2 relaxation time and delayed gadolinium‐enhanced MRI of cartilage (dGEMRIC) of human patellar cartilage at 1.5 T and 9.4 T: Relationships with tissue mechanical properties
Authors: Lammentausta E. , Kiviranta P. , Nissi M.J. , Laasanen M.S. , Kiviranta I. , Nieminen M.T. , Jurvelin J.S.
Published: December 2005

Quantitative magnetic resonance imaging (MRI) techniques have been developed for noninvasive assessment of the structure of articular cartilage. T2 relaxation time is sensitive to the integrity and orientation of the collagen network, while T1 relaxation time in presence of Gd‐DTPA2− (dGEMRIC) reflects the proteoglycan content of cartilage. In the present study, human patellar cartilage samples were investigated in vitro to determine the ability of MRI parameters to reveal topographical variations and to predict mechanical properties of cartilage at two different field strengths. T2 and dGEMRIC measurements at 1.5 T and 9.4 T were correlated with the static and dynamic compressive moduli at six anatomical locations of the patellar surface. Statistically significant linear correlations were observed between MRI and mechanical parameters at both field strengths, especially between T2 and Young's modulus. No significant difference was found between the T2 measurements at different field strengths in predicting mechanical properties of the tissue. Topographical variation of T2 values at both field strengths was similar to that of Young's moduli. The current results demonstrate the feasibility of quantitative MRI, particularly T2 mapping, to reflect the mechanical properties of human patellar cartilage at both field strengths. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:366–374, 2006
Influence of polyethylene creep behavior on wear in total hip arthroplasty
Authors: Penmetsa Janaki R. , Laz Peter J. , Petrella Anthony J. , Rullkoetter Paul J.
Published: December 2005

After total hip arthroplasty (THA), polyethylene acetabular liner creep occurs quickly and serves to increases head–liner contact area and decrease contact pressures. What effect these early changes in contact mechanics will have on the wear behavior of the articulation remains unclear, and hence, selection or modification of polyethylene materials for optimal creep and wear performance is impossible. The objective of this study was to determine the influence of polyethylene creep behavior on volumetric wear and linear creep and wear penetration during simulated gait loading conditions. A finite element model of THA articulation was developed, and simultaneous numerical creep and wear simulation was performed to 10 million gait cycles with three levels of polyethylene creep behavior. Long‐term volumetric wear and penetration were surprisingly unaffected by the polyethylene creep behavior due to the competing decrease in contact pressures coupled with increased contact area. In addition, variation in contact mechanics with the creep levels studied was only noteworthy in the initial postoperative period; after 1 million gait cycles, peak contact pressures and areas were within 13% regardless of the creep material behavior selected. Femoral head size had considerable impact on wear and penetration, while liner thickness primarily affected only early penetration. These results suggest that polyethylene creep behavior plays a major role in early penetration, but has little influence on the more important long‐term volumetric wear. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:422–427, 2006
A robot‐assisted study of intrinsic muscle regulation on proximal interphalangeal joint stiffness by varying metacarpophalangeal joint position
Authors: Li Zong‐Ming , Davis Gregg , Gustafson Norm P. , Goitz Robert J.
Published: December 2005

The tightness of intrinsic hand muscles is a common cause of finger joint stiffness. The purposes of this study were to develop a robot‐assisted methodology to obtain torque–angle data of a finger joint, and to investigate the regulation of the intrinsic muscles on finger joint stiffness. Our robot system features the integration of a low payload robot arm, a controller, and a force/torque transducer. The system provided highly reproducible torque–angle curves. Torque–angle data of the proximal interphalangeal joint with the metacarpophalangeal joint at 0 and 60 degrees were obtained from eight asymptomatic hands. The torque–angle curve shifted with the position of the metacarpophalangeal joint. As the metacarpophalangeal joint flexion angle changed from 60 to 0 degrees, the equilibrium of the proximal interphalangeal joint increased more than 20 degrees, and joint stiffness increased more than 50%. The dependence of the stiffness of the proximal interphalangeal joint on metacarpophalangeal joint position supports the regulatory role of the intrinsic muscles on finger joint mechanics. This regulatory mechanics is likely amplified in hands with intrinsic muscle tightness, justifying the commonly used Bunnell Intrinsic Tightness Test. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:407–415, 2006
Changes in gene expression and protein distribution at different stages of mechanically induced disc degeneration—an in vivo study on the New Zealand white rabbit
Authors: Omlor Georg W. , Lorenz Helga , Engelleiter Karl , Richter Wiltrud , Carstens Claus , Kroeber Markus W. , Guehring Thorsten
Published: December 2005

The objective of the study was to improve the biological understanding of degenerative disc disease using a rabbit model in which different stages of disc degeneration are induced by variation of the duration of loading with an external compression‐device applying 2.4 MPa. Gene expression and protein distribution were analyzed in controls and after 1, 28, and 56 days of hyperphysiologic loading. To evaluate extracellular matrix genes, quantitative real‐time reverse‐transcriptase polymerase chain reaction was applied for collagen I, collagen II, biglycan, decorin, fibromodulin, fibronectin, aggrecan, and osteonectin. As representatives of catabolic, anticatabolic, and anabolic factors, matrix metalloproteinase‐13 (MMP‐13), tissue inhibitor of matrix metalloproteinase‐1 (TIMP‐1), and bone morphogenetic protein‐2 (BMP‐2) were chosen. To evaluate protein distribution, immunohistochemistry was performed for collagen I, collagen II, and BMP‐2/4. Matrix gene expression was characterized by two major developments: collagen I and II, biglycan, and decorin showed early elevation followed by later downregulation to control levels, whereas fibromodulin, fibronectin, aggrecan, and osteonectin showed continuous upregulation or remained at similar levels. Induction of MMP‐13 gene expression was found in degenerated discs. TIMP‐1 and BMP‐2 were elevated immediately after hyperphysiologic loading and presented highest levels in the 56‐day group. Immunohistochemistry showed less collagen II and BMP‐2/4 positive cells after compression. In conclusion, elevated matrix gene expression represents an early cellular response to hyperphysiologic loading. As degeneration progresses, some matrix genes increase upregulation, whereas others start downregulation. Continuous upregulation of catabolic, anticatabolic, and anabolic factors indicates their important role in the degeneration process. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:385–392, 2006
Ablative versus non‐ablative treatment of perioral rhytides. A randomized controlled trial with long‐term blinded clinical evaluations and non‐invasive measurements
Authors: Hedelund L. , Bjerring P. , Egekvist H. , Haedersdal M.
Published: January 2006

Background and Objective

To compare efficacy and side effects of CO2 laser resurfacing and intense pulsed light (IPL) rejuvenation for treatment of perioral rhytides.

Methods

Twenty‐seven female subjects with perioral rhytides (class I–III) were randomly treated with either CO2 laser or IPL (three monthly treatments). Efficacy was evaluated by patient self‐assessments and blinded photographs up to 12 months postoperatively. Side effects were assessed clinically. Non‐invasive measurements included: trans epidermal water loss (TEWL), skin reflectance, skin elasticity, and ultrasound.

Results

CO2 laser resurfacing resulted in higher degrees of patient satisfaction and clinical rhytide reduction compared to IPL rejuvenation up to 12 months postoperatively (patient evaluations, P < 0.05) (observer evaluations, P < 0.008). Laser‐induced side effects included erythema, dyspigmentation, and milia whereas no side effects were observed after IPL rejuvenation. Non‐invasive measurements showed a significant higher reduction of the subepidermal low‐echogenic band in CO2 laser treated areas versus IPL treated areas (12 months postoperatively, P < 0.001). Skin elasticity (expressed as Young's modulus) increased in both groups (P = ns). One month postoperatively a significant increase in TEWL values (P < 0.009) and skin redness% (P < 0.02) was found in CO2 laser treated patients versus IPL treated patients. No significant differences were seen in skin pigmentation% during the observation period.

Conclusion

CO2 laser resurfacing induces a significantly higher degree of clinical rhytide reduction followed by considerably more side effects compared to IPL rejuvenation in a homogeneous group of patients. Lasers Surg. Med. 38:129–136, 2006. © 2006 Wiley‐Liss, Inc.
Antioxidant agents transiently inhibit aneuploidy progression in Li‐Fraumeni cell strains
Authors: Kraniak Janice M. , Abrams Judith , Nowak James E. , Tainsky Michael A.
Published: December 2005

Cultured human fibroblasts from patients with the Li‐Fraumeni syndrome (LFS) containing heterozygous germline p53 mutations develop genomic instability, loss of the wild‐type p53 allele, and immortalize at a low frequency. Since genomic instability and phenotypic change are observed in presenescent cells without specific exposure to mutagens, we hypothesized that reactive oxygen species (ROS) produced during normal cell metabolism coupled with deficient p53 dependent DNA damage repair pathways make a significant contribution to immortalization related parameters. To test this hypothesis, three LFS cell strains (MDAH087, MDAH041, and MDAH172) were exposed to five compounds with demonstrated antioxidant properties for ≥85% of their proliferative lifetimes. Agent effectiveness was evaluated every five passages during subculturing by analyzing aberrant chromosome number, anchorage independent growth (AIG), and p16 expression. Cytogenetic analysis revealed that of the five antioxidants tested, only oltipraz was significantly effective in transiently delaying a shift to hyperdiploidy in all three cell strains. However, treated populations were not different from untreated controls when measured in the last 10% of their lifetimes. Additionally, no differences were observed in AIG and p16 expression in antioxidant treated or untreated control populations. Epidemiological studies, in vitro and in vivo experimentation and some clinical trials have suggested that antioxidants may inhibit the progression of cancer and other mutation related diseases. This data, however, does not support the hypothesis that the antioxidants tested have chemopreventive potential in cancers that develop genomic instability due to loss of p53. © 2005 Wiley‐Liss, Inc.
Microsatellite instability in multiple nonfamilial malignancies
Authors: Niv Eva , Bomstein Yonit , Bernheim Joelle , Lishner Michael
Published: December 2005

Development of multiple tumors of different histopathologic types may suggest a profound generalized genetic defect, such as malfunction of DNA mismatch repair (MMR) mechanism. Defects in this mechanism are best reflected in microsatellite instability (MSI). We aimed to determine the role of MSI in a group of patients with dual malignancies and compared the data with that of patients with a single malignancy. Fifty patients were enrolled in the study, of whom 16 patients developed both solid and hematologic nonfamilial malignancies, 18 patients developed a single matched hematologic malignancy, and 16 a single matched solid malignancy. Five microsatellite markers were replicated by polymerase chain reaction (PCR) after DNA extraction from paraffin‐embedded tissue blocks and analyzed by the GeneScan Analysis Software. The MSI‐high phenotype was defined as instability in at least 40% of the examined loci. A higher prevalence of MSI‐high phenotype was found in patients with dual malignancies (31.3%) compared with patients with single hematologic (5.6%) or solid malignancy (6.3%) (P = 0.0498 and 0.07, respectively). In conclusion, defects in DNA MMR mechanism may have an important role in the development of multiple sporadic nonfamilial malignancies. © 2005 Wiley‐Liss, Inc.
O6‐alkylguanine‐DNA alkyltransferase gene polymorphisms and the risk of primary lung cancer
Authors: Chae Myung Hwa , Jang Jin‐Sung , Kang Hyo‐Gyoung , Park Jae Hyung , Park Jung Min , Lee Won Kee , Kam Sin , Lee Eung Bae , Son Ji‐Woong , Park Jae Yong
Published: December 2005

O6‐alkylguanine‐DNA alkyltransferase (AGT) plays an important role in the repair of O6‐alkylguanine adducts, which are major mutagenic lesions produced by environmental carcinogens. Polymorphisms in the AGT gene may affect the capacity to repair DNA damage and thereby have influence on individual's susceptibility to smoking‐related cancer. To test this hypothesis, we investigated the potential association of AGT polymorphisms (485C > A, Leu53Leu (C > T) and Leu84Phe] with the risk of lung cancer in a Korean population. The AGT genotypes were determined in 432 lung cancer patients and in 432 healthy controls who were frequency‐matched for age and gender. The 485 AA genotype was associated with a significantly increased risk for overall lung cancer as compared with the 485 CC genotype and the combined 485 CC + CA genotype, respectively (adjusted odds ratio (OR) = 1.83, 95% confidence interval (CI) = 1.12–2.99, P = 0.02, and Bonferroni corrected P‐value (Pc) = 0.04; and adjusted OR = 1.67, 95% CI = 1.05–2.66, P = 0.03, respectively). When the lung cancer cases were categorized by the tumor histology, the 485 AA genotype was associated with a significantly increased risk of adenocarcinoma (AC) and small cell carcinoma (SmCC), respectively, as compared with the combined 485 CC + CA genotype (adjusted OR = 2.54, 95% CI = 1.39–4.66, P = 0.003; and adjusted OR = 2.19, 95% CI = 1.06–4.55, P = 0.04, respectively). However, the genotype distributions of the Leu53Leu and Leu84Phe polymorphisms were not significantly different between the lung cancer cases and the controls. On a promoter assay, the 485C > A polymorphism did not have an effect on the promoter activity of the AGT gene. These results suggest that the effect of the AGT 485C > A polymorphism on the risk of lung cancer may be secondary to linkage disequilibrium (LD) with either another AGT variant or with a true susceptibility gene, and that the AGT 485C > A polymorphism could be used as a marker for the genetic susceptibility to lung cancer. © 2005 Wiley‐Liss, Inc.
Cyclooxygenase isozymes are expressed in human myeloma cells but not involved in anti‐proliferative effect of cyclooxygenase inhibitors
Authors: Ding Jie , Tsuboi Kazuhito , Hoshikawa Hiroshi , Goto Rieko , Mori Nozomu , Katsukawa Michiko , Hiraki Emi , Yamamoto Shozo , Abe Masahiro , Ueda Natsuo
Published: December 2005

Considering possible tumorigenic activity of cyclooxygenase (COX) isozymes in myeloma, we examined expression levels of COX‐1 and ‐2 in seven human myeloma cell lines (ARH‐77, IM‐9, RPMI‐8226, HPC, HS‐Sultan, TSPC‐1, and U‐266). As analyzed by reverse transcriptase‐polymerase chain reaction (RT‐PCR), all the cell lines constitutively expressed COX‐1, while COX‐2 levels markedly varied among different cell lines. Induction of COX‐2 by phorbol ester was observed in RPMI‐8226 and HPC cells. In contrast, COX‐2 was constitutively expressed in ARH‐77 and IM‐9 cells. Moreover, the high expression level of COX‐2 protein in ARH‐77 cells was verified by Western blotting. Intact cells of ARH‐77 converted 14C‐labeled arachidonic acid to prostaglandin E2, F2α, and D2, and this activity was dose‐dependently inhibited by selective COX‐2 inhibitors (SC‐58125 and NS‐398), a non‐selective COX inhibitor (indomethacin), and relatively high concentrations of a selective COX‐1 inhibitor (SC‐560). These COX inhibitors also suppressed the proliferation of ARH‐77 cells, but significant suppression was seen only at 100 µM, a much higher concentration than those sufficient for the COX inhibition. Moreover, proliferation of the myeloma cells lacking COX‐2 was also suppressed by 100 µM of SC‐58125. These results suggested that the anti‐proliferative effect of the COX inhibitors is independent of the inhibition of COX‐2. © 2005 Wiley‐Liss, Inc.
Phosphodiesterase 5 (PDE 5) inhibitors for the treatment of male erectile disorder: Attaining selectivity versus PDE6
Authors: Pissarnitski Dmitri
Published: December 2005

The role of phosphodiesterase type 5 (PDE5) in the mechanism of male erection has been well understood, and several drugs inhibiting this enzyme are being used for the treatment of erectile dysfunction (ED). Discovery of inhibitors with improved selectivity versus other PDE isozymes could lead to drugs with improved safety profile. Achievement of selectivity versus PDE6, co‐inhibition of which results in disturbances of color perception, remains the most challenging aspect of current drug discovery programs. The present review describes several case studies, where significant (>100 fold) selectivity versus PDE6 has been attained via investigation of structure–activity relationships (SAR). Special attention is given to the chemical routes leading to novel chemotypes and allowing efficient exploration of their SAR's. Strategies for attaining inhibitor selectivity discussed below may be applicable for other drug discovery programs. © 2005 Wiley Periodicals, Inc. Med Res Rev
Compressible Navier–Stokes equations with vacuum state in the case of general pressure law
Authors: Fang Daoyuan , Zhang Ting
Published: December 2005

In this paper, we consider the one‐dimensional compressible isentropic Navier–Stokes equations with a general ‘pressure law’ and the density‐dependent viscosity coefficient when the density connects to vacuum continuously. Precisely, the viscosity coefficient µ is proportional to ρθ and 0<θ<1, where ρ is the density. And the pressure P = P(ρ) is a general ‘pressure law’. The global existence and the uniqueness of weak solutions is proved, and a decay result for the pressure as t→ + ∞ is given. It is also proved that no vacuum states and no concentration states develop, and the free boundary do not expand to infinite. Copyright © 2006 John Wiley & Sons, Ltd.
Photon transport with a localized source in locally convex spaces
Authors: Lisi Meri , Totaro Silvia
Published: December 2005

This paper deals with the study of a mathematical model of photon transport in an interstellar cloud where a localized source is present. The source is represented by a Dirac delta functional. The problem is studied in the setting of locally convex spaces. By means of the theory of semigroups on locally convex spaces and the adjoint approach, we prove existence and uniqueness of the solution. Copyright © 2006 John Wiley & Sons, Ltd.
Optimal control of non‐linear chemical reactors via an initial‐value Hamiltonian problem
Authors: Costanza V. , Neuman C. E.
Published: December 2005

The problem of designing strategies for optimal feedback control of non‐linear processes, specially for regulation and set‐point changing, is attacked in this paper. A novel procedure based on the Hamiltonian equations associated to a bilinear approximation of the dynamics and a quadratic cost is presented. The usual boundary‐value situation for the coupled state–costate system is transformed into an initial‐value problem through the solution of a generalized algebraic Riccati equation. This allows to integrate the Hamiltonian equations on‐line, and to construct the feedback law by using the costate solution trajectory. Results are shown applied to a classical non‐linear chemical reactor model, and compared against suboptimal bilinear‐quadratic strategies based on power series expansions. Since state variables calculated from Hamiltonian equations may differ from the values of physical states, the proposed control strategy is suboptimal with respect to the original plant. Copyright © 2005 John Wiley & Sons, Ltd.
Synthesis, characterization and properties of organoclay‐modified polyurethane/epoxy interpenetrating polymer network nanocomposites
Authors: Jia Qingming , Zheng Maosheng , Shen Renjie , Chen Hongxiang
Published: December 2005

organoclay‐modified polyurethane/epoxy interpenetrating network nanocomposites (oM‐PU/EP nanocomposites) were prepared by adding organophilic montmorillonite (oMMT) to interpenetrating polymer networks (IPNs) of polyurethane and epoxy resin (PU/EP) which had been prepared by a sequential polymerization technique. Wide‐angle X‐ray diffraction (WAXD) and transmission electronic microscopy (TEM) analysis showed that the interpenetrating process of PU and EP improved the exfoliation and dispersion degree of oMMT. The effects of the NCO/OH ratio (isocyanate index), the weight ratio of PU/EP and oMMT content on the phase structure and the mechanical properties of the oM‐PU/EP nanocomposites were studied by tensile testing and scanning electronic microscopy (SEM). Water absorption tests showed that the PU/EP interpenetrating networks and oMMT had synergistic effects on improvement in the water resistance of the oM‐PU/EP nanocomposites. Differential scanning calorimetry (DSC) analysis showed that PU was compatible with EP and that the glass transition temperature (Tg) of the oM‐PU/EP nanocomposites increased with the oMMT content up to 3 wt%, and then decreased with further increasing oMMT content. The thermal stability of these nanocomposites with various oMMT contents was studied by thermogravimetric analysis (TGA), and the mechanism of thermal stability improvement was discussed according to the experimental results. Copyright © 2005 Society of Chemical Industry
Synthesis and characterization of new ferroelectric liquid‐crystalline cyclic oligosiloxanes containing methyleneoxymethylene spacers
Authors: Sołtysiak Joanna T , Czupryński Krzysztof , Drzewiński Witold
Published: December 2005

The synthesis of side‐chain liquid‐crystalline oligocyclosiloxanes containing methyleneoxymethylene spacers, two different mesogenic cores (including biphenyl phenyl carboxylate or biphenyl fluorophenyl carboxylate groups) and chiral tails is presented. Differential scanning calorimetry, optical polarizing microscopy and X‐ray diffraction measurements reveal liquid‐crystalline properties for all of the synthesized monomers and oligomers. All cyclic oligosiloxanes exhibit enantiotropic smectic A and chiral smectic C phases. The mesogenic properties of the cyclic oligomers and side‐chain liquid‐crystalline precursor are discussed. Copyright © 2005 Society of Chemical Industry
High‐yield controlled syntheses of polysilanes by the Wurtz‐type reductive coupling reaction
Authors: Jones Richard G , Holder Simon J
Published: December 2005

The factors that determine the Wurtz‐type reductive coupling of dichloroorganosilanes by alkali metals are reviewed. A strong recommendation is advanced for carrying out all such polysilane syntheses in tetrahydrofuran at ambient temperature, conditions under which the reaction gives far higher yields and generally much narrower product molecular weight distributions. The higher yields are attributed to the ability of the solvent to sequester the sodium ion and thereby stabilize the anionic chain carriers. The bimodal molecular weight distributions of the product polymers, which are ubiquitous when such reactions are carried out in high‐boiling‐point aromatic solvents under reflux, as is common practice, are attributed to it being a defect‐diffusion‐controlled polymerization at the alkali metal surface. The narrower molecular weight distributions that result from syntheses in tetrahydrofuran are attributed to the suppression of defect diffusion rates at lower temperatures. Copyright © 2005 Society of Chemical Industry