bluuebunny/crossref_metadata_2025 huggingface dataset:
Osteonecrosis of the jaws in patients treated with bisphosphonates – histomorphologic analysis in comparison with infected osteoradionecrosis
Authors: Hansen Torsten , Kunkel Martin , Weber Achim , James Kirkpatrick C.
Published: February 2006

Background:  Patients treated with bisphosphonates because of bone metastases have been shown to develop osteonecrosis of the jaws. In the present study, we examined the histologic findings of these cases. As similarities between this disorder and infected osteoradionecrosis (IORN) are described, both lesions were compared.

Methods:  We investigated eight patients with bisphosphonate treatment and osteonecrosis (four female, four male; median age: 65.6 years; cancer: multiple myeloma in five patients, breast cancer in three patients; mandibular involvement in five patients, maxillar involvement in three cases), and 10 patients suffering from IORN (all male; median age: 61.3 years; cancer: squamous cell carcinoma in nine patients, adenoid cystic carcinoma in one patient; mandibular involvement in all cases). Multicentric and bilateral involvement was common in the bisphosphonate group. Histologically, the bone revealed diffuse and patchy areas of necrosis in the bisphosphonate group, while in IORN osteonecrosis was larger and not diffusely distributed.

Results:  In all cases, we found Actinomyces attached to the necrotic bone tissue. In five of eight bisphosphonates cases, and in six of 10 IORN cases, numerous osteoclasts could be detected close to vital bone exhibiting signs of bone resorption. Pseudoepitheliomatous hyperplasia (PH) was revealed in five of eight bisphosphonate patients, and in seven of 10 IORN patients.

Conclusion:  We conclude that Actinomyces is involved in the chronic, non‐healing inflammatory processes as a characteristic feature of both diseases. Together with the associated presence of increased osteoclast numbers, we suggest that both factors may be involved in osteolytic mechanisms.
Expression of TNF‐α in oral lichen planus treated with fluocinolone acetonide 0.1%
Authors: Thongprasom Kobkan , Dhanuthai Kittipong , Sarideechaigul Wilairat , Chaiyarit Ponlatham , Chaimusig Mantharop
Published: February 2006

Background:  Oral lichen planus (OLP) is a common chronic inflammatory disease involving T cells‐mediated immunity. Tumor necrosis factor (TNF)‐α has been reported to be involved in the disease process. The purpose of this study was to investigate the effect of fluocinolone acetonide in orabase (FAO) 0.1% on the expression of TNF‐α in patients with OLP.

Methods:  Eighteen Thai patients with atrophic or erosive OLP were recruited. Biopsy specimens were taken before and 1 month after treatment with FAO 0.1% and sent for histopathologic examination where they were immunohistochemically stained with antibody to TNF‐α. Twenty normal mucosa specimens were identically processed. Oral squamous cell carcinoma tissue was used as a positive control for TNF‐α expression, whereas OLP sections without primary antibody were served as negative control.

Results:  Sixteen of 18 cases (88.89%) of OLP exhibited positive staining for TNF‐α. Most of the TNF‐α was observed in the mononuclear cells. Ten cases (55.56%) of OLP demonstrated TNF‐α expression in keratinocytes. The number of mononuclear cells positive for TNF‐α before the treatment with FAO 0.1% in orabase was statistically higher than that after the treatment (P = 0.000) and in the normal mucosa (P = 0.000). Moreover, the number of mononuclear cells after treatment with FAO 0.1% in orabase was statistically lower than before the treatment (P = 0.000).

Conclusion:  Our study exhibited that TNF‐α may be associated with the immunopathogenesis of OLP in Thai patients and FAO 0.1% had an effect on the reduction of TNF‐α expression.
Correlation of basic fibroblast growth factor expression with the invasion and the prognosis of oral squamous cell carcinoma
Authors: Hase Takashi , Kawashiri Shuichi , Tanaka Akira , Nozaki Shinichi , Noguchi Natsuyo , Kato Koroku , Nakaya Hiromitsu , Nakagawa Kiyomasa
Published: February 2006

Background:  The aim of this study was to evaluate the relationship between the expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor‐1 (FGFR‐1) in cancer cells and fibroblasts at the invasive front of oral squamous cell carcinoma (OSCC), and the pathologic and clinical characteristics.

Methods:  Sections of 61 biopsy specimens of primary OSCC were immunostained to assess the expression of bFGF and FGFR‐1 in cancer cells and fibroblasts at the invasive front.

Results:  The bFGF and FGFR‐1 expressions in the cancer cells were evident in all specimens, whilst, in fibroblasts, they were detected in 41 (67%) of 61 specimens. These expressions in the fibroblasts occurred notably more often in high‐invasive OSCC specimens than low‐invasive OSCC specimens. The prevalence of bFGF and FGFR‐1 expressions in cases with lymph node metastasis was significantly higher (P < 0.05) than in cases without metastasis. Moreover, these expressions were well correlated with patient prognosis.

Conclusion:  This study concludes that bFGF and FGFR‐1 expressions in fibroblasts at the invasive front are linked to the mode of invasion and the prognosis in OSCC.
Analysis of apoptosis‐associated genes and pathways in oral cancer cells
Authors: Gibson Sandra , Shillitoe Edward J.
Published: February 2006

Background:  Cancer cells can resist apoptosis that is induced by stimuli such as detachment or differentiation, but may be more susceptible to apoptosis when exposed to chemotherapeutic drugs. The pattern of gene expression that produces this phenotype is unknown.

Methods:  We compared gene expression patterns of normal human epidermal keratinocytes (NHEK cells) and the oral cancer cell line Tu183 when the cells were exposed to different apoptosis‐inducing stimuli.

Results:  Pathway analysis revealed that the phenotype difference could be best explained by the simultaneous existence of both proapoptosis and antiapoptosis signals in the cancer cells. Microarray analysis, supported by immunoblotting, showed that one gene that was likely to be involved in the proapoptosis signal was TNFRSF5, which encodes the receptor CD40. When Tu183 cells were exposed to the CD40 ligand they showed apoptosis, while NHEK cells did not.

Conclusions:  The effects of different apoptotic stimuli on normal cells and oral cancer cells can be explained by expression of proapoptosis genes, including the gene that encodes CD40.
Effects of Stress on Susceptibility and Severity of Inflammation in Adjuvant‐induced Arthritisa
Authors: CHOVER‐GONZALEZ ANTONIO J. , HARBUZ MICHAEL S. , TEJEDOR‐REAL PURIFICACION , GIBERT‐RAHOLA JUAN , LARSEN PHILIP J. , JESSOP DAVID S.
Published: February 2006

ABSTRACT: We have utilized the open field and learned helplessness (LH) models of psychological stress to determine whether a differential response to stress can affect the severity of adjuvant‐induced arthritis (AA) within a single rat strain. In response to open field stress, the corticosterone response of the low emotivity rats was significantly lower than that of the high emotivity rats. In spite of the differential corticosterone response to stress, no significant difference was found in paw volumes between the AA high and low emotivity groups. In another study, rats were subjected to a learned LH paradigm and separated into two groups based on failed (LH+) or successful (LH‐) avoidance. Plasma corticosterone levels in response to avoidable foot shock in the LH‐ rats were significantly greater than in the LH+ group. Following injection with adjuvant, paw inflammation occurred earlier and was more severe in the LH‐ rats compared to the LH+ group. These data show that rats with a greater tendency to avoid foot shock have more severe inflammation, despite having a greater corticosterone response to stress. We conclude that an increased corticosterone response to stress does not affect susceptibility to or severity of inflammation in AA. Indeed, in the LH model a more robust response to stress is associated with increased inflammation and earlier onset of the disease.
Role of the Sympathetic Adrenal System in the Pathogenesis of the Insulin Resistance Syndrome
Authors: LANDSBERG LEWIS
Published: February 2006

ABSTRACT: The pathophysiology of the various manifestations of Syndrome X has been poorly understood. A possible mechanism involves stimulation of the sympathetic nervous system (SNS). Insulin plays an important role in the relationship between dietary intake and SNS activity. Because insulin‐mediated glucose uptake in central hypothalamic neurons regulates SNS activity in response to dietary intake, a hypothesis was developed that links the hyperinsulinemia of obesity to sympathetic stimulation, the latter exerting a prohypertensive effect mediated by the kidney, the heart, and the vasculature. Evidence in support of this hypothesis has been obtained from the Normative Aging Study (NAS) in which a relationship between insulin (and glucose) and the SNS, and between insulin and SNS activity and blood pressure was demonstrated. The characteristic dyslipidemia in NAS subjects, moreover, was related to insulin and epinephrine. As reported in other studies, insulin level was directly associated with low HDL and high triglyceride levels. An independent inverse association was also noted between urinary epinephrine excretion and lipid levels: high epinephrine excretion rates were associated with high HDL and low triglyceride levels and, conversely, low epinephrine excretion was associated with low HDL and high triglycerides. In the NAS, therefore, increased SNS activity contributes to hypertension while diminished adrenal medullary activity contributes to the low HDL and high triglyceride levels commonly seen in association with hypertension.
Apoptosis and Necrosis in Cerebrovascular Disease
Authors: SNIDER B. JOY , GOTTRON FRANK J. , CHOI DENNIS W.
Published: February 2006

ABSTRACT:Neuronal death following ischemic insults has been thought to reflect necrosis. However, recent evidence from several labs suggests that programmed cell death, leading to apoptosis, might additionally contribute to this death. We have used bothin vitroandin vivomodels to study the role of apoptosis in ischemic cell death. Some features of apoptosis (TUNEL staining, internucleosomal DNA fragmentation, sensitivity to cycloheximide) were observed following transient focal ischemia in rats. Brief transient focal ischemia was followed by delayed infarction more than 3 days later; this delayed infarction was sensitive to cycloheximide. A cycloheximide‐sensitive component of neuronal cell death was also observed in cultured murine neocortical neurons deprived of oxygen‐glucose in the presence of glutamate receptor antagonists. This presumed ischemic apoptosis was attenuated by caspase inhibitors, or by homozygous deletion of thebaxgene. Neurons may undergo both apoptosis and necrosis after ischemic insults, and thus it may be therapeutically desirable to block both processes.
Electrical Injury through the Eyes of Professional Electricians
Authors: TKACHENKO TATIANA A. , KELLEY KATHLEEN M. , PLISKIN NEIL H. , FINK JOSEPH W.
Published: February 2006

ABSTRACT: This paper presents the first results of an attitudinal survey that was conducted among professional electricians in order to explore their knowledge and beliefs related to occupational electrical injury. Four hundred eighty‐one out of 1200 questionnaires were returned and analyzed. The presented statistical and qualitative data reflect electricians' personal experiences with electrical injury, their communication patterns around electrical trauma, their understanding of possible electrical injury sequelae, their safety beliefs and attitudes towards occupational dangers, and the reasons for their occupational choice. We expect that the results of this study will enhance our understanding of the psychological profile, environment, and culture of electrical workers. The collected data may also help to identify those at risk for poor outcome after electrical injury and determine a new set of risk factors to be taken into account by medical professionals, social workers, and union/utility training officers.
Functional Reconstruction following Electrical Injury
Authors: ORGILL DENNIS P. , PRIBAZ JULIAN J.
Published: February 2006

ABSTRACT: Worldwide, high voltage electrical injury continues to cause significant morbidity, disability, and mortality despite improvements in electrical safety. Joule heating and cell membrane disruption are two mechanisms important in understanding the pathophysiology of electrical injury. The degree of tissue damage is often more extensive than initially perceived on clinical exam. Using modern reconstructive techniques, the functional outcome of electrical injury victims can be improved. The type of reconstruction selected for each injury can be selected from a number of options from the reconstructive ladder. Donor site considerations, risks of the surgery, team experience, and patient preference are important factors in this selection.
Experience of Urgent Reconstruction of Electrical Injuries
Authors: ZHU ZHI‐XIANG , XU XIAO‐GUANG , ZHANG YUE‐AN , CHEN LI‐YING , LIU TIAN‐YI , LI WEI‐PING
Published: February 2006

ABSTRACT: Although there have been great advances in the treatment of electrical injuries in the last 20 years, the extremity loss ratio in electrical injuries remains at an unacceptably high level. The primary reason for this is the progressive tissue necrosis and enlargement of the necrosis in the wound. The goal in this study is to examine possible ways to break the necrotic malignancy circle and save the form and function of damaged extremities. As a result of systematic experimental and clinical research, a comprehensive urgent reconstruction alternative for electrical injuries has been proposed. The alternative includes the following principles: debriding the wound as early as possible after injury; preserving as much as possible the vital tissue structures, such as nerve, vessels, joints, tendons, and bone, even when they have undergone devitalization or local necrosis; transplanting these vital tissues during the first surgery if the functional reconstruction requires; nourishing the wound bed by covering with tissue flaps that have rich blood supply; improving flap survival by continuous irrigations with a compound medicine beneath the flaps for a 24‐ to 72‐hour period after surgery; providing general treatment with vasoactive agents and antibiotics.

This paper summarizes our experience of using this method in the treatment of 105 electrical injury patients (a total of 309 wounds) in the time period from 1 January 1986 to 31 December 1996. Satisfying results were obtained, with the extremity loss ratio decreasing to 7% as compared to 41.5% during the 10 years preceding 1984 at the same hospital. Thus, the urgent comprehensive reconstruction alternative presented here is an effective and workable method to manage electrical injuries.
Statistical Methods for Developmental Toxicity: Analysis of Clustered Multivariate Binary Data
Authors: RYAN LOUISE , MOLENBERGHS GEERT
Published: February 2006

Abstract: This paper discusses some of the statistical issues that arise from developmental toxicity studies, wherein pregnant mice are exposed to chemicals in order to assess possible adverse effects on developing fetuses. We begin with a review of some current approaches to risk assessment, based on NOAELs, and provide justification for the use of methods based on dose‐response models. Due to the hierarchical nature of the data, such models are more complicated in the present context than, say, in cancer studies. For example, multivariate binary outcomes arise when each fetus in a litter is assessed for the presence of malformations and/or low birth weight. We describe a multivariate exponential family model that works well for these data and that is flexible in terms of allowing response rates to depend on cluster size. Maximum likelihood estimation of model parameters and the construction of score tests for dose effect are briefly discussed. Results are illustrated with data from several NTP studies.
Cardiovascular Pathways: Socioeconomic Status and Stress Effects on Hypertension and Cardiovascular Function
Authors: PICKERING THOMAS
Published: February 2006

Abstract: In westernized societies there is a consistent and continuous gradient between the prevalence of cardiovascular disease (including both coronary heart disease and stroke) with SES, such that people from lower SES have more disease. Several studies have examined the roles of the major cardiovascular risk factors for explaining this gradient. There is a strong SES gradient for smoking, which parallels the gradient in disease, but the gradients for hypertension and cholesterol are weak or absent. Central obesity and physical inactivity may also be contributory factors. In the United States there is a strong association between SES and race, and it is suggested that the higher prevalence of hypertension and cardiovascular disease in blacks may be attributed to psychosocial factors, including those related to SES. The possible pathways by which SES affects cardiovascular disease include effects of chronic stress mediated by the brain, differences in lifestyles and behavior patterns, and access to health care. At the present time, the second of these is the strongest candidate; the effects of stress have been little studied.
Transplantation of Pancreatic Islets Contained in Minimal Volume Microcapsules in Diabetic High Mammalians
Authors: CALAFIORE RICCARDO , BASTA GIUSEPPE , LUCA GIOVANNI , BOSELLI CARLO , BUFALARI ANDREA , BUFALARI ANTONELLO , CASSARANI MARIA PAOLA , GIUSTOZZI GIAN MARIO , BRUNETTI PAOLO
Published: February 2006

ABSTRACT: To minimize technical problems relating to excessive size (600–800μ in diameter) of standard alginate microcapsules (CSM) for pancreatic islet graft immunoisolation, we have developed two novel minimal volume, chemically identical, capsule prototypes (MVC): 1) coherent microcapsules (CM), and 2) medium‐size microcapsules (300–400μ, MSM). CM, which envelop each individual islet within a thin alginate hydrogel cast, are prepared by emulsification, whereas MSM are made by atomizing the islet‐alginate suspension through a special microdroplet generator. Upon graft into diabetic rodents, CM have shown to immunoprotect both allo‐ and xenogeneic nondiscordant islets, and restored normoglycemia. In higher mammals, at sub‐therapeutic doses, CM fully immunoprotected islet allografts (pig→pig), but only temporarily xenografts (dog→pig). We then used MSM to immunoisolate canine islet allografts in the peritoneal cavity of dogs with spontaneous insulin‐dependent diabetes. Of three grafted dogs, two showed full remission of hyperglycemia with insulin withdrawal. MSM could represent an intermediate solution between CSM and CM for peritoneal immunoisolated islet transplants.
Antigen Presentation Pathways for Immunity to Islet Transplants: Relevance to Immunoisolation
Authors: GILLA RONALD G.
Published: February 2006

ABSTRACT: Tremendous advances have been made over the past several years in the development of diverse biocompatible materials and structural designs for the implantation of immunoisolated cells and tissues. This area of bioengineering has clear application to insulin‐dependent diabetes for which the implantation of micro‐ or macroencapsulated pancreatic islets or surrogate β cells has great potential therapeutic benefit. This discussion concentrates on three antigen‐specific immunologic processes that impede the application of islet transplantation as a therapy for insulin‐dependent diabetes: (1) Allograft immunity, (2) Xenograft immunity, and (3) Autoimmune pathogenesis of Type I diabetes. Special emphasis is placed on the potential impact of these immune pathways on immunoisolated tissues.
Factors in Xenograft Rejection
Authors: ROBSON SIMON C. , AM ESCH JAN SCHULTE , BACH FRITZ H.
Published: February 2006

ABSTRACT: Important mechanisms underlying immediate xenograft loss by hyperacute rejection (HAR), in the pig‐to‐primate combination, have been recently delineated. There are now several proposed therapies that deal with the problem of complement activation and xenoreactive natural antibody (XNA) binding to the vasculature that have been shown to prevent HAR. However, vascularized xenografts are still lost, typically within days, by delayed xenograft rejection (DXR), alternatively known as acute vascular rejection (AVR). This process is characterized by endothelial cell (EC) perturbation, localization of XNA within the graft vasculature, host NK cell and monocyte activation with platelet sequestration and vascular thrombosis. Alternative immunosuppressive strategies, additive anti‐complement therapies with the control of any resulting EC activation processes and induction of protective responses have been proposed to ameliorate this pathological process.

In addition, several potentially important molecular incompatibilities between activated human coagulation factors and the natural anticoagulants expressed on porcine EC have been noted. Such incompatibilities may be analogous to cross‐species alterations in the function of complement regulatory proteins important in HAR. Disordered thromboregulation is potentially relevant to the progression of inflammatory events in DXR and the disseminated intravascular coagulation seen in primate recipients of porcine renal xenografts. We have recently demonstrated the inability of porcine tissue factor pathway inhibitor (TFPI) to adequately neutralize human factor Xa (FXa), the aberrant activation of both human prothrombin and FXa by porcine EC and the failure of the porcine natural anticoagulant, thrombomodulin to bind human thrombin and hence activate human protein C. The enhanced potential of porcine von Willebrand factor to associate with human platelet GPIb has been demonstrated to be dependent upon the isolated A1 domain of von Willebrand factor. In addition, the loss of TFPI and vascular ATPDase/CD39 activity following EC activation responses would potentiate any procoagulant changes within the xenograft. These developments could exacerbate vascular damage from whatever cause and enhance the activation of platelets and coagulation pathways within xenografts resulting in graft infarction and loss.

Analysis of these and the other putative factors underlying DXR should lead to the development and testing of genetic approaches that, in conjunction with selected pharmacological means, may further prolong xenograft survival to a clinically relevant extent.
Overview of Extracorporeal Liver Support Systems and Clinical Results
Authors: McLAUGHLIN BRIAN E. , TOSONE CHRISTINE M. , CUSTER LINDA M. , MULLON CLAUDY
Published: February 2006

ABSTRACT: Patients with acute liver failure (ALF) continue to have an almost 50% mortality raate despite improvements associated with the use of orthotopic liver transplantation (OLT). Numerous ex vivo methods have been developed in attempts to improve patient survival. These methods scan be divided into three groups: detoxification (e.g., dialysis adsorption, plasma exchange), which only provides excretory function; ex vivo liver perfusion (e.g., whole organ or tissue perfusion), which provides some metabolic function; and bioartificial or cell‐based systems, which combine elements of the first two methods. Clinical trials have shown minimal efficacy of the various detoxification methods in terms of ALF patient survival, while the relative sucess of OLT has shown the importance of providing metabolic as well as excretory functions. Attempts to provide those additional functions with ex vivo tissue perfusion have been fraught with complications such as clothing and acute tissue rejection, leading to the conceptual development of cell‐based bioreactor sytems. A number of these bioartificial systems have been clinically evaluated, and the preliminary patient survival rates have encouraged further work in this area.
Bioreactors for Hybrid Liver Support: Historical Aspects and Novel Designs
Authors: BUSSE BENEDIKT , GERLACH JÖRG C.
Published: February 2006

ABSTRACT: A novel bioreactor construction has been designed for the utilization of hepatocytes and sinusoidal endothelial cells. The reactor is based on capillaries for hepatocyte aggregate immobilization. Three separate capillary membrane systems, each permitting a different function are woven in order to create a three dimensional network. Cells are perfused via independent capillary membrane compartments. Decentralized oxygen supply and carbon dioxide removal with low gradients are possible. The use of identical parallel units to supply hepatocytes facilitates scale up.

In vitro studies demonstrate long‐term external metabolic function in primary isolated hepatocytes within bioreactors. These systems are capable of supporting essential liver functions. Animal experiments have verified the possibility of scaling‐up the bioreactors for clinical treatment. However, since there is no reliable animal model for investigation of the treatment of acute liver failure, the promising results obtained from these studies have limited relevance. The small number of clinical studies performed so far is not sufficient to reach conclusions about improvements in the therapy of acute liver failure. Although important progress has been made in the development of these systems, various hepatocyte culture models and bioreactor constructions are being discussed in the literature, which indicates competition in this field of medical research.

An overview, which emphasizes the development of hepatocyte culture models for bioreactors, subsequent In vitro studies, animal studies, and clinical application, is also provided.
Human Nerve Pathology Caused by Different Mutational Mechanisms of the PMP22 Gene
Authors: GABREËLS‐FESTEN ANNEKE , VAN DE WETERING RUDI
Published: February 2006

ABSTRACT: The study of the morphological phenotypes in patients with different mutations of the PMP22 gene gives additional insights into the role of the protein in myelin function. The pathology in young patients is in some aspects different from the pathology in older patients, providing essential and additional information about the early disease processes in humans induced by different PMP22 mutational mechanisms.

Duplication of chromosome 17p11.2, causing an overexpression of the PMP22 gene, results in early hypermyelination. This suggests that PMP22 has a function in establishing the proper myelin thickness, probably in response to an axonal signal. Demyelination and remyelination with gradual formation of onion bulbs occur apparently as secondary processes, but these processes subside at the end of the first decade. PMP22 missense mutations usually result in a more severe phenotype showing an early hypomyelination and onion bulb formation, likely disturbing normal myelin formation and maintenance. The morphological differences with duplication cases underline the essential difference in pathogenesis between duplication and missense mutations despite the large overlap in clinical and electrophysiological phenotypes. The reciprocal deletion of chromosome 17p11.2, resulting in an underexpression of the PMP22 gene, is responsible for the clinical phenotype of HNPP. As the nerve abnormalities in HNPP show a marked resemblance to the changes in experimental and genuine human entrapment neuropathies, it is postulated that PMP22 has a function in adhesion of myelin lamellae, preventing mutual longitudinal sliding. Deletion of one PMP22 copy results in increased susceptibility for mechanical forces through which already minor nerve injuries might induce a longitudinal displacement of myelin lamellae. The frame shift mutation Gly94(insG) combines a loss of function like in the common deletion HNPP with a mild CMT1 phenotype, likely inducing a (mild) toxic gain of function by disturbing myelin formation and maintenance, comparable to the effect in missense mutations.
Molecular Diagnostic Testing in Charcot‐Marie‐Tooth Disease and Related Disorders: Approaches and Results
Authors: De JONGHE P. , NELIS E. , TIMMERMAN V. , LÖFGREN A. , MARTIN J‐J. , VAN BROECKHOVEN C.
Published: February 2006

ABSTRACT: The inherited neuropathies of the peripheral nervous system are clinically and genetically a heterogeneous group of disorders. Molecular genetic studies have made major breakthroughs in unraveling the underlying gene defects, and DNA diagnosis can now be offered to a large number of families with distinct forms of hereditary peripheral neuropathies. With the currently available technology, however, molecular genetic diagnosis still remains a labor‐intensive and costly procedure. We have developed an algorithm for mutation screening based on clinical phenotype, electrophysiological findings, and the relative frequencies of mutations in the distinct peripheral myelin genes.
Overcoming Cellular Immunity to Prolong Adenoviral‐Mediated Gene Expression in Sciatic Nerve
Authors: JANI AGNES , MENICHELLA DANIELA , JIANG HUIYUAN , CHBIHI TAIBI , ACSADI GYULA , KAMHOLZ JOHN , SHY MICHAEL E.
Published: February 2006

ABSTRACT: In a previous report, we demonstrated that a first generation (E1‐ and E3‐deleted) recombinant adenovirus can transduce expression of the E. coli lacZ gene into Schwann cells, both in vitro and in vivo, suggesting that this method might be useful for future therapy of peripheral neuropathy, including CMT1. Adenoviral‐mediated gene transfer was limited, however, by demyelination and Wallerian degeneration at the site of virus injection, as well as by attenuation of viral gene expression over time. In our current work we have optimized adenoviral‐mediated gene expression after intraneural injection into sciatic nerve. Using an improved injection protocol, peak expression of lacZ occurs between 10 and 14 days after injection of 2‐week‐old animals, decreases thereafter, and there is minimal associated tissue injury. In contrast, very few adenoviral‐infected Schwann cells are found in nerves of adult animals 10 days after injection, probably due to immune clearance of viral‐infected cells. Consistent with this notion, high levels of lacZ are found in sciatic nerve 30 days after injection of adult SCID mice, which have a genetic defect in both cellular and humoral immunity, of adult β2 microglobulin‐deficient mice (β2 M −/−), which have a genetic defect in cellular immunity, or of adult mice treated with the immunosuppressing agent FK506. In addition, adenoviral‐infected Schwann cells co‐cultured with axons in vitro, in the absence of a host immune response, ensheath axons and express lacZ for at least 8 weeks. These data thus demonstrate that expression of first generation recombinant adenovirus in sciatic nerve in adult mice, as in other tissues, is limited mainly by the host cellular immune response to the virus, which can be overcome by attenuation of host cell‐mediated immunity. Adenoviral vectors might thus be used to modulate Schwann cell gene expression in patients with peripheral neuropathy after appropriate immunosuppression.
Abnormal Schwann Cell‐Axon Interactions in CMT Neuropathies: The Effects of Mutant Schwann Cells on the Axonal Cytoskeleton and Regeneration‐Associated Myelination
Authors: SAHENK ZARIFE
Published: February 2006

ABSTRACT: Preferential distal axonal loss is a common feature of Charcot‐Marie‐Tooth (CMT) hereditary neuropathies. The general hypothesis tested here is that the axonal loss in these disorders is due to perturbed Schwann cell‐axon interactions resulting from primary Schwann genetic defects. The nerve xenograft model was used to study the local influence of mutant Schwann cells derived from patients on axonal properties and the regeneration‐associated myelination process. Sural nerve segments from individuals with PMP22 duplications or deletions and point mutations, as well as Cx32 point mutations were grafted into cut ends of the sciatic nerve of nude mice and studied at different time intervals after grafting. CMT1A and CMTX xenografts examined at 16 weeks show that the nude mouse axons within the proximal part of grafts demonstrate a significant increase in axonal area with an increase in the neurofilament and membranous organelle density compared to distal graft and distal host segments. A preferential distal axonal loss associated with a perpetual axonal atrophy, degeneration, and axonal sprouting was observed over time with increasing frequency at 8 to 16 weeks. A distal summation of the pathology, as evidenced by a greater amount of fiber loss in the distal graft segments, was present similar to that observed in patients. These alterations were seen to a lesser extent in PMP22 deletion or point mutation xenografts and were not observed in controls. Collectively, these findings show that Schwann cells bearing the PMP22 or Cx32 genetic defects cause major perturbations in Schwann cell‐axon interactions emphasizing the role of axonal component in the pathogenesis of hereditary neuropathies.
Numerical Analysis and Experiment on a Plasma Torch with Hollow Electrodes for Hazardous Waste Treatment
Authors: HUR MIN , CHO HONG , HONG SANG HEE
Published: February 2006

ABSTRACT: Thermal plasma characteristics of a nontransferred plasma torch with hollow electrodes are numerically and experimentally investigated in the atmospheric condition. Distributions of temperature, velocity, and mass flux in the air thermal plasma are calculated both inside and outside the torch by varying its operational and geometrical conditions, such as gas flow rate, input current, and electrode diameter. The dynamic and static behaviors of arc voltage depending on these operational and geometrical variables are experimented in a small‐scale plasma torch, from which a similarity criterion representing a semi‐empirical relationship between the arc voltage and other variables is determined to predict the operational characteristics of high‐power plasma torches with hollow electrodes for hazardous waste treatment.
Effect of metal particles oxidation during the APS on the wettability.
Authors: ESPIE G. , FAUCHAIS P. , HANNOYER B. , LABBE J.C. , VARDELLE A.
Published: February 2006

ABSTRACT: Investigations have been carried out to study the in flight oxidation of iron particles during Atmospheric Plasma Spray (APS) process. The molten particles are quenched by an inert gas (argon) and collected in a experimental set‐up especially developed for this purpose. With this set‐up, more than 90 wt% of the particles are collected. Investigation methods such as XRD, Mössbauer spectroscopy and SEM‐EDX are used to determine the amount and the distribution of oxide formed. The results indicate that wüstite (FeO) is present at the surface and also in the core of the particles. This oxide phase represents about 12 wt% of the collected particles and is stable over time. Sessile drop studies of molten iron on alumina and zirconia substrates are carried out to simulate the wetting of oxidized iron particles during coating formation. It is found that the oxidation state of iron particles during APS has a significant effect on the observed contact angles. A decrease of the contact angle is observed in the case of oxidized iron particles.
FUNDAMENTAL CONSIDERATIONS IN THE DEPOSITION OF BARIUM FERRITE FILMS IN AN INDUCTIVELY COUPLED PLASMA REACTOR
Authors: VIDAL EDGAR E. , TAYLOR PATRICK R.
Published: February 2006

ABSTRACT: The production of barium ferrite films has been studied using an Inductively Coupled Plasma (ICP) Reactor. Solutions containing dissolved salts of iron and barium in water were used as precursors. The solution was atomized in the hot region of the plasma and the resulting vapors and carrier gases impinged on a substrate holder. Vycor glass #7913 was used as the substrate material due to its properties and low cost. Pure argon and combinations of argon and oxygen were used as plasma gases. Power of the plasma torch was varied as well as the rotational speed, the distance of the substrate from the plasma torch exit and the molar ratio of iron to barium in the feed solution. Deposited films were characterized using Scanning and Transmission Electron Microscopy, Vibrating Sample Magnetometery and X‐Ray Diffraction. Example results are given that show that it is possible to grow films of barium hexaferrite on Vycor glass. Films that were amorphous after deposition were heat treated in an oxygen atmosphere to crystallize the barium hexaferrite. A mathematical model that describes the momentum, heat and mass transfer in the reactor was developed. It was expected that using a near atmospheric pressure ICP would demonstrate technological and economical advantages over existing methods.
NON THERMAL PLASMA TREATMENT FOR OXIDATION OF HALOGENATED ORGANIC MOLECULES.
Authors: Seguin D. , Brisset J. L. , Estel L.
Published: February 2006

ABSTRACT: In this paper, the use of the gliding are technique to degrade pollutant molecules of 4,chlorophenol and 2,4,6 trichlorophenol is presented. The technique itself is presented as well as the optimisation of the process, implemented on sodium hydroxide solutions. The optimum parameters were applied to the degradation of chlorophenols. The evolution of concentrations was measured thanks to HPLC. It was shown that, in the case of chlorophenol, a zero order reaction took place while in the case of trichlorophenol the reaction was devided in two steps. First stages of the determination of the reaction products and reaction schemes are presented and discussed.
Predictability of Mutant Sequences: Relationships between Mutational Mechanisms and Mutant Specificity
Authors: RIPLEY LYNN S.
Published: February 2006

ABSTRACT: Spontaneous mutations are rare and are produced by multiple biochemical mechanisms. Nonetheless, studies of these mechanisms have revealed striking examples in which mutational specificity can be regularly related to a characteristic of the surrounding DNA sequence and/or the enzymes participating in mutagenesis. Thus, to an increasing degree the DNA sequences of mutants are “predictable.” This report considers some examples of predictable sequence changes, evidence for their contribution to mutagenesis in populations, and how the predictability of mutant sequences may be useful to improve our interpretation of the molecular course of evolution from DNA sequence comparisons.
The Role of the Striatopallidal and Extended Amygdala Systems in Drug Addiction
Authors: KOOB GEORGE F.
Published: February 2006

ABSTRACT: Evidence Suggests that the acute reinforcing actions of drugs of abuse may be mediated by specific elements of the striatopallidal and extended amygdala systems. These include the shell of the Nucleus accumbens, the central nucleus of hte amygdala, and the sublenticular extended amygdala. Chronic administration of drugs of abuse, including cocaine, amphetamines, nicotine, alcohol, and tetrahydrocannabinol leads to an increasing dysregulation of brain reward systems that is characterized by decreases in reward function. Withdrawal from chronic administration of cocaine, amphetamine, nicotine, alcohol, and tetrahydrocannabinol raises thresholds for brain stimulation reward. Neurochemical elements in the extended amygdala may mediate these changes, including decreases in dopamine and serotonin neurotransmission in the nucleus accumbens and increases in the brain‐stress neurotransmitter, corticotropin‐releasing factor, in the central nucleus of the amygdala. The combination of decreases in function of neurotransmitters involved in the positive‐reinforcing properties of drugs of abuse with recruitment of brain‐stress systems within the extended amygdala provides a powerful mechanism for allostatic changes in hedonic set point that can lead to the compulsive drug‐seeking and drug‐taking behavior characteristic of addiction.
Excess Catecholamine Syndrome: Pathophysiology and Therapya
Authors: RUPP HEINZ
Published: February 2006

ABSTRACT: In addition to genetic factors, lifestyle has a predominant influence on primary hypertension and noninsulin‐dependent diabetic mellitus (NIDDM). We initiated studies using radiotelemetry for characterizing molecular events linked with excess calorie intake and psychologic stress. An increased calorie intake was associated with raised (p < 0.05) systolic and diastolic blood pressure as well as heart rate independent of day‐night cycle. Sympathetic activity was in excess when related to the unchanged motility. The hyperkinetic hypertension is expected to result in adverse remodeling of resistance vessels and to aggravate insulin resistance. To examine adverse effects of psychological stress, rats were subjected to intermittent food pellet feeding. Urinary catecholamines and cardiac norepinephrine stores were increased (p < 0.05). The depressed (p < 0.05) rate of Ca2+ uptake of sarcoplasmic reticulum is expected to contribute to cellular Ca2+ overload. These lifestyle influences strengthen the notion of an excess catecholamine syndrome which requires selective reduction of sympathetic outflow of the brain by I1‐receptor agonists.
SCH 51344, An Inhibitor of RAS/RAC‐Mediated Cell Morphology Pathway
Authors: KUMAR C. CHANDRA , OHASHI KAZUMASA , NAGATA KYOKO , WALSH AMY , BAR‐SAGI DAFNA , MIZUNO KENSAKU
Published: February 2006

Abstract: RAS interacts with multiple targets in the cell and controls at least two signaling pathways, one regulating extracellular signal‐regulated kinase (ERK) activation and the other controlling membrane ruffling formation. These two pathways appear to act synergistically to cause transformation. Human smooth muscle α‐actin promoter is repressed in RAS‐transformed cells and derepressed in revertant cell lines, suggesting that it is a sensitive marker to follow phenotypic changes in fibroblast cells. SCH 51344 is a pyrazoloquinoline derivative identified on the basis of its ability to derepress α‐actin promoter in RAS‐transformed cells. Previous studies have shown that SCH 51344 is a potent inhibitor of RAS transformation. However, SCH 51344 had very little effect on the activities of proteins in the ERK pathway, suggesting that it inhibits RAS transformation by a novel mechanism. Recently, we have demonstrated that SCH 51344 specifically blocks membrane ruffling induced by activated forms of H‐RAS, K‐RAS, N‐RAS, and RAC. Treatment of fibroblast cells with this compound had very little effect on RAS‐mediated activation of ERK and JUN kinase activities. SCH 51344 was effective in inhibiting the anchorage‐independent growth of Rat‐2 fibroblast cells transformed by the three forms of oncogenic RAS and RAC V12. These results indicate that SCH 51344 inhibits a critical component of the membrane ruffling pathway downstream from RAC and suggest that targeting this pathway may be an effective approach to inhibiting transformation by RAS and other oncogenes.
The Practical Success of Impedance Techniques from an Historical Perspective
Authors: SCHWAN HERMAN P.
Published: February 2006

Abstract: Future problems are based on achievements of the past. They may be unresolved problems of a more basic nature or future practical applications made possible by recent technical innovations. The introductory part of this paper deals with recent history and its many significant advances. This is followed by a survey of the bioimpedance field. Past advances include contributions of the bioimpedance field to electrophysiology, biophysics, and biochemistry. More practical contributions include the data necessary for the development of diathermy techniques and modern dosimetry in the field of electromagnetic biohazards. A large array of practical applications relate to monitoring physiological events such as impedance plethysmography, impedance encephalography, impedance tomography, and body water, lung, and heart function parameters. Unresolved problems of a basic nature include topics that relate to mechanisms responsible for observed dielectric dispersions and membrane biophysics. Practical applications that can now be realized include several new electronic laboratory diagnostic techniques. Tissue spectroscopy of small biopsy samples and tissue culture samples should permit rapid extraction of valuable cellular data. This can be done for both normal and abnormal states, thus providing new diagnostic techniques. Possible sophistication of the Coulter counter principle should permit rapid investigations of many individual cell parameters, including cellular shape, using multielectrode techniques (microimpedance tomography). The theory of field‐evoked force effects is well established now and can be used to develop electronic cell manipulation and new electronic cell sorting technologies. Additional significant practical applications to the biomedical field are now possible.
In Vivo and In Situ Ischemic Tissue Characterization Using Electrical Impedance Spectroscopya
Authors: CASAS O. , BRAGÓS R. , RIU P. J. , ROSELL J. , TRESÀNCHEZ M. , WARREN M. , RODRIGUEZ‐SINOVAS A. , CARREÑO A. , CINCA J.
Published: February 2006

Abstract: The investigation of processes of ischemia in different organ tissues is very important for the development of methods of protection and preservation during surgical procedures. Electrical impedance spectroscopy was used to distinguish between different tissues and their degree of ischemia. We describe mathematical methods used to adjust experimental data to Cole‐Cole models for one‐circle and two‐circle impedance loci and a study of the main parameters for representing the behavior of ischemia in time. In vivo and in situ postmortem measurements of different tissues from pigs are shown in the 100 Hz to 1 MHz range. The Cole parameters that best characterize the ischemia are R0 and fc.
A Meta‐analysis of Published Studies Concerning the Validity of Thoracic Impedance Cardiography
Authors: RAAIJMAKERS E. , FAES TH. J. C. , SCHOLTEN R. J. P. M. , GOOVAERTS H. G. , HEETHAAR R. M.
Published: February 2006

Abstract: Our aim was to provide a meta‐analysis of the literature concerning the validation of thoracic impedance cardiography (TIC) and to explain variations in reported results from differences in the studies. One hundred fifty‐four studies (164 Fisher's Z‐transformed correlation coefficients) comparing measurements of cardiac output or related parameters from TIC and a reference method were analyzed. Papers were classified according to differences in TIC methodology, reference method, and subject characteristics. Pooling using the random‐effects method yielded an overall correlation of r= 0.82 (95% confidence interval: 0.80‐0.84). ANOVA revealed a significant influence of the reference method and the subject characteristics on the correlation coefficient. In cardiac patients, the correlation was significantly decreased. No influence of the applied TIC methodology was found. Conclusion: TIC might be useful for trend analysis of different groups of patients. However, since the reference method was of significant influence, differences between TIC and the reference method are incorrectly attributed to TIC alone.