bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression and mutations of p53 in salivary gland tumours
Authors: Kärjä Vesa J. , Syrjänen Kari J. , Kurvinen Anna‐Kaisa , Syrjänen Stina M.
Published: April 2006

A series of 219 salivary gland tumours (103 carcinomas and 116 benign tumours) were analysed for p53 protein expression using immunohistochemistry, and for mutations in p53 gene using non‐radioactive single strand conformation polymorphism (SSCP). p53 expression was present in 36% (42/116) of the benign tumours and in 54% (56/103) of the carcinomas. The highest prevalence of p53 expression was found in adenoid cystic carcinomas (69%). followed by mucoepidermoid carcinomas (67%). Of the benign tumours, pleomorphic adenomas showed the highest prevalence of p53 positivity (41%). In malignant tumours, expression of p53 bore no correlation to local recurrence, metastatic disease or survival of the patients. Exons 5 through 9 were analysed and four mutations were found in 20 cases of p53‐immunopositive tumours and two in 20 p53‐negative tumours. Each of the exons 5.6 and 8/9 had two mutations, whereas no mutations were detected in exon 7.
Autopsy findings in the tongues of 20 patients with AIDS
Authors: Leonard N. , McCreary C. , Flint S. F. , Mabruk M. J. E. M. F. , Mulcahy F. , Toner M.
Published: April 2006

An extensive examination of the tongue was performed at autopsy in 20 consecutive patients who had died with AIDS. Abnormalities in the tongue were detected in 18 (90%) of the cases; the commonest lesions were ulceration (11), candidosis (8) and small foci of hyperkeratosis (10). The most extensive lesions were caused by Aspergillus infection (1), non‐Hodgkin's lymphoma juxtaposed with Kaposi's sarcoma (1), herpetic infection (1) and candidosis (5). The disease causing death was identified in the tongue in two cases. There was a surprisingly low prevalence of oral hairy leukoplakia. which may be related to anti‐viral or retroviral therapy.
Burning mouth syndrome (BMS) and the concept of alexithymia – a preliminary study
Authors: Jerlang B. B.
Published: April 2006

Twenty women suffering from burning mouth syndrome (BMS) were rated with regard to alexithymic traits, depressive symptoms and anxiety: values were compared to disability level assessed by interviews. Results confirm earlier reports that BMS symptomatology is associated with depression and anxiety. The majority of patients were rated as alexithymic and. supported by interview data; these results indicate that somatization should be taken into consideration during clinical evaluation of BMS symptoms. The study included a psychological analysis of the communication pattern in the patient‐doctor relationship, leading to the assumption that the patient's appeal for somatic treatment, dependency and hopelessness may activate defensive reactions in the dentist. Such reactions can be either rejection of. or compliance with, the patient's demands. The importance of a differentiated assessment and treatment approach for these patients is emphasized. Due to lack of control data the report should be viewed as a pilot study.
Features of odontogenesis and expression of cytokeratins and tenascin–C in three cases of extraosseous and intraosseous calcifying odontogenic cyst
Authors: Lukinmaa Pirjo‐Liisa , Leppaniemi Anu , Hietanen Jarkko , Allemanni Giorgio , Zardi Luciano
Published: April 2006

To characterize further the nature of calcifying odontogenic cyst (COC), we studied histologically and immunohistochemically an extraosseous and two intraosseous lesions. The extraosseous COC was in continuity with the stratified squamous epithelium of the alveolar mucosa. Immunostaining with monoclonal antibodies showed reactivity of both low‐ and high‐molecular‐weight cytokeratins, the degree of coexpression decreasing with the increasing morphological diversity of the cyst/tumour epithelium. Staining for the matrix glycoprotein tenascin‐C was seen not only in the connective tissue, where its distribution patterns corresponded to the stage of hard tissue formation, but also in epithelial elements. The staining patterns were analogous to those described during normal tooth formation. Both the morphological characteristics and expression patterns of the various cytokeratin types and tenascin‐C implied that COC represents a pathological counterpart of normal odontogenesis. In the case of the extraosseous COC, the correspondence could he traced back to early stages of tooth development.
The articular disc surface in different functional conditions of the human temporomandibular joint
Authors: Marchetti C. , Bernasconi G. , Reguzzoni M. , Farina A.
Published: April 2006

The peripheral discal tissue and the surface covering layer have been studied in normal and in variously damaged human temporomandibular joint discs. In the normal disc the tissue consisted of dense bundles of fibers and rare fibrocytes. The surface of the disc was covered by a regular basophilic and electron‐dense layer. These morphological characteristics persisted also in some pathological discs in which fibrous derangements had already occurred in the deep parts. In very deformed and damaged discs associated with serious functional anomalies, the superficial discal tissue consisted of rare fibers dispersed in a loose ground substance and of an increased number of cells. The superficial coating was formed by an irregular dense lamina and aggregates of various materials containing cellular debris, vesicles, filaments and amorphous components. These deposits are probably due to degeneration processes of discal tissue. This investigation suggests that the superficial discal tissue and the covering layer are together involved in maintaining the functional properties of the articular surfaces. Their structural modification in severe functional anomalies leads to failure in the maintenance of nonadherence conditions and to deterioration of the functional defect.
The radiopaque lesion: A diagnostic consideration
Authors: Bender L. B. , Mori Katsuei
Published: April 2006

Abstract This study attempts to designate that some periapical and periodontal radiopacities can be caused by inflamed or necrotic pulps and periodontitis. An hypothesis is offered to explain the formation of a periapical sclerotic lesion. The increase in periapical bone density can often mask an occult granulomatous lesion and it can be obscured by inadvertently superimposing tori over apical radiolucencies. The increased reactive periapical sclerosis is not necessarily clue to an osteitis. This is especially true of dense trabecular bone patterns that are noted in cases of occlusal stress and in periodontitis. It is questionable whether the use of the terms condensing osteitis or sclerosing osteitis is appropriate. Endodontic or periodontic therapy in cases associated with increased bone density produce a normalization of the bone trabeculae. The lesions that do not respond to the specific treatment may be due to anatomic landmarks, increase in functional stimuli producing excessive bone production, local and systemic disorders. Diagnostic features of the radiopaque lesion are discussed.
Effect of masticatory stimulation on dentoalveolar ankylosis after experimental tooth replantation
Authors: Andersson Lars , Lindskog Sven , Blomlöf Leif , Hedström Karl‐Goran , Hammarström Lars
Published: April 2006

Abstract Dentoalveolar ankylosis (replacement resorption) is a serious complication after replantation of avulsed teeth. The purpose of the present study was to investigate the influence of masticatory stimulation on dentoalveolar ankylosis after replantation of avulsed teeth. Monkey upper incisors were extracted, air‐dried for 1 h, endodontically treated and replanted. No splinting was used. One group of monkeys was given hard pelleted food, while another group was given soft diet during a healing period of 8 wk. The periodontal conditions were evaluated histologically with a morphometrical method. The replanted teeth of the monkeys given the hard pelleted food had significantly less ankylosis and a larger area of the root surrounded by a normal periodontal membrane than the teeth from the monkeys given a soft diet. In conclusion, development of ankylosis seemed to be partially prevented or reduced by masticatory stimulation.
A retrospective study of direct pulp capping with calcium hydroxide compounds
Authors: Hørsted Preben , Søndergaard Børge , Thylstrup Anders , El Attar Kefaya , Fejerskov Ole
Published: April 2006

Abstract Direct pulp capping with calcium hydroxide compounds was performed on 510 human teeth. Pulp had been exposed as a result of cavity preparation in 70% of cases, and by removal of carious dentine in 15%. For the remaining 15% of the cases no information on the cause of exposure was available. The teeth were clinically and radiographically controlled 1, 3, 6 and 12 months after treatment and at the stopping date. 245 cases were available for clinical examination. Information on the remaining cases was obtained from the records. Using the life table method, the trial time was calculated for each case as the time from dale of treatment to the date of failure, the date of last contact or the stopping date. The data were analyzed according to cause of perforation, age of patient and type of tooth. Five‐year survival was 82% No significant difference in survival was observed between non‐carious and small carious exposures. Young teeth and molars showed a higher survival rate when the longer observation periods were considered.
The role of the necrotic periodontal membrane in cementum resorption and ankylosis
Authors: Lindskog Sven , Pierce Angela M. , Blomlöf Leif , Hammarström Lars
Published: April 2006

Abstract Teeth replanted with non‐vital periodontal membranes demonstrate a high incidence of root resorption and ankylosis. It has been suggested that necrotic periodontal membrane remnants actively stimulate resorption of the resistant cementum layer. The aim of this study was to examine resorption and ankylosis patterns following replantation of teeth with chemically denuded root surfaces and, by extrapolation from these data, to suggest a role for the necrotic periodontal membrane in resorption and ankylosis.

Monkey incisors were replanted after endodontic therapy and immersion in 10% sodium hypochlorite. Teeth were either examined with scanning electron microscopy at intervals from 1 day to 8 wk, or subjected to light microscopic examination, using a morphometrical evaluation technique, at 8 wk post‐replantation.

Only a few macrophage‐like cells, in relation to shallow resorption lacunae, were observed by 8 wk. Histologically, the alveolar bone had approached an apparently intact cementum surface in 93% of the morphometrically recorded points. This bone appeared to lie in close approximation to the cementum surface.

Denuding the root surface of periodontal membrane prior to replantation demonstrated the resistance of the cementum to colonization and resorption in the absence of stimulation from necrotic periodontal membrane remnants. Furthermore, it revealed that bone replacing the periodontal membrane space grew from the alveolus towards the cementum, to which it appeared unable to fuse due to the absence of significant resorption. Thus, removal of a non‐vital periodontal membrane may result in slower destruction of tooth substance following replantation of teeth with severely damaged periodontal membranes.
Resistance to fracture of restored endodontically treated teeth
Authors: Trope Martin , Maltz David O. , Tronstad Leif
Published: April 2006

Abstract Endodontically treated teeth were restored by 8 different methods. Copper rings were filled with commercial hard setting cement and the teeth were placed into the cement to the level of the cemento‐enamel junction. The teeth were grouped according to restorative methods, mounted in an Instron T.T. machine and subjected to a slowly increasing compressive force until fracture occurred. The force of fracture for each tooth was recorded and the results in the various groups compared. All teeth fractured in a similar manner, irrespective of restorative method used. Preparation of a post space in the roots significantly weakened the teeth. Cementation of a steel parapost with zinc oxyphosphate cement did not significantly strengthen the teeth. Filling the post space and the access cavity with a composite resin following acid etching of the root canal and cavity walls strengthened the teeth more than other methods used to restore them. This finding may be of clinical importance, for instance in the restoration of endodontically treated young teeth with incomplete root formation and wide root canals.
Transient hemiparesis following mandibular nerve anesthesia
Authors: Weinberg Aaron , Shohat Shimon , Stabholz Adam , Findler Gidon
Published: April 2006

Abstract A case of transient hemiparesis subsequent to a contra‐lateral local anesthetic injection into the pterygomandibular space is reported. This is believed to be the first documented case of such a complication following an inferior dental nerve block. An anatomic explanation is presented to explain the probable route‐the anesthetic agent may have taken and the C.N.S. areas it may have implicated.
Successful self‐replantation of avulsed tooth with 42‐year follow‐up
Authors: Fuss Zvi
Published: April 2006

Abstract This report presents a case of a 55‐year‐old woman who was hit in the mouth 42 years ago. The maxillary right central incisor was avulsed. The patient's mother replanted the tooth within 10–20 minutes and “splinted” it with aluminium foil from a cigarette package and a piece of cardboard. Clinical and radiographic examination after 42 years revealed a slightly discolored asymptomatic right central incisor. The root canal space was obliterated and no signs of root resorption or periapical radiolucency were observed.
Prognosis of luxated permanent teeth — the development of pulp necrosis
Authors: Andreasen Frances M. , Pedersen Bo Vestergaard
Published: April 2006

AbstractA population of 400 patients, comprising 637 luxated permanent teeth was studied prospectively with respect to the development of pulp necrosis after luxation injuries. The patients were treated for traumatic dental injuries over a period of 10 years. While initial treatment was provided according to established treatment guidelines by the attending oral surgeon at the emergency room, follow‐up examination and treatment was provided by one oral surgeon. It appeared that pulp necrosis occurred soon after injury, within 3 months after concussion, within the 1st yr after subluxation and extrusion, and might be diagnosed up to 2 yr after lateral‐ and intrusive luxation. While many factors, when considered one at a time, were found to have a significant or nearly significant died on the development of pulp necrosis (i.e. type of injury, age of patient, stage of root development, degree of dislocation, reduction/repositioning procedure, type of fixation, restorations in place at the lime of injury), a multivariate regression analysis revealed that when the type of injury (diagnosis) and stage of root development were taken into account, the effect of other factors was no longer significant. The risk of pulp necrosis increased with the extent of injury, i.e. concussion and subluxation represented the least risk, followed in ascending order by extrusive‐, lateral‐, and intrusive luxation. Moreover, teeth with completed root formal ion demonstrated a greater risk of pulp necrosis than teeth with incomplete root formation. No treatment effect could be demonstrated. However, as treatment was performed according to established guidelines, which might introduce bias, it would appear justified to conduct randomized clinical studies in order to determine the value of different forms of treatment (e.g. reduction and fixation of luxated teeth) to improve the prognosis with respect to the development of pulp necrosis after injury. In conclusion, the major factors influencing development of pulp necrosis after luxation injuries appear to be the extent of the initial injury to the pulp and periodontium, as reflected by the type of luxation, and the repair potential of the injured tooth, as reflected by the stage of root development.
Experimental internal resorption in monkey teeth
Authors: Wedenberg Cecilia , Lindskog Sven
Published: April 2006

Abstract Internal resorption is a rare pathological finding except in pulpectomized deciduous teeth. Although its etiology is largely unknown, infection and trauma have been suggested in a number of cases. The aim of this study was to explore the possibility of provoking internal resorption in vivo, to study etiological factors such as trauma and infection, and to describe the cells colonizing the walls of the pulp chamber. Monkey incisors were opened, injected with Freund's complete adjuvant and sealed or left open to the oral cavity. After varying observation periods, the teeth were extracted and prepared for examination with scanning electron microscopy, microradiography, light microscopy and enzyme histochemistry. Colonization of the walls of the pulp chamber by macrophage‐like cells was observed in both experimental groups. However, it appeared to be transient in Unsealed, non‐infected teeth and more extensive and prolonged in the open, infected teeth. In sections of pulp tissue a tartrate‐resistant acid phosphatase activity characteristic of mineralized tissue resorbing cells was evident.

It is suggested that internal resorption may be divided into a transient type and a progressive type, the latter requiring a continuous stimulation by infection.
The relationship between dentin microhardness and tubule density
Authors: Pashley David , Okabe Atsuko , Parham Phillip
Published: April 2006

Abstract The purpose of this study was to determine the possible correlation between dentin microhardness and dentin tubule density in normal human permanent teeth. A new technique was developed which permitted serial determinations of the micro‐hardness and tubule density of the same group of tubules, beginning near to the dentino‐enamel junction and progressing to the pulp chamber. The results show that there is a highly statistically significant inverse correlation between dentin micro‐hardness and tubular density. Tubular density increased as the pulp chamber was approached. This was associated with a decrease in dentin microhardness, presumably due to a decrease in the amount of intertubular dentin and an increase in individual tubular diameter.
The periapical index: A scoring system for radiographic assessment of apical periodontitis
Authors: Ørstavik Dag , Kerekes Kasmer , Eriksen Harald M.
Published: April 2006

Abstract A scoring system for registration of apical periodontitis in radiographs is presented. The system is termed the periapical index (PAI) and provides an ordinal scale of 5 scores ranging from 1 (healthy) to 5 (severe periodontitis with exacerbating features). Its validity is based on the use of reference radiographs of teeth with verified histological diagnoses. Results from studies involving 11 observers and 47 selected radiographs document that the PAI system is reasonably accurate, reproducible and able to discriminate between sub‐populations. It may also allow for results from different researchers to be compared. The system may be suitable for the analysis of periapical radiographs in epidemiological studies, in clinical trials and in retrospective analyses of treatment results in endodontics.
Mandibular molar with three distal root canals
Authors: Quackenbush Larry E.
Published: April 2006

Abstract An unusual case is presented in which there were three canals in the distal root of a mandibular first permanent molar. The anomaly was not detectable radiographically, but could be important during root canal treatment. The variation may be related to the occurrence of a contralateral three‐rooted molar seen in the patient.
Sensitivity of dentin to chemical stimuli
Authors: Pashley David H.
Published: April 2006

Abstract Numerous chemical stimuli have been used to click pain from exposed dentin. Most of the effective chemicals share a common denominator; they arc all very hypertonic. Dentin surfaces covered with a smear layer are much less responsive to hypertonic solutions than dentin devoid of a smear layer. These observations support the hydrodynamic theory of dentin sensitivity. The most important variables influencing the efficacy of chemical stimuli include: ionic composition, presence or absence of calcium, sodium or potassium, pH and osmolality (tonicity). Although hypertonic solutions of sucrose or CaCl2 can be useful qualitative stimuli, the theoretical objections to using them for quantitative evaluation of dentinal sensitivity seem to far out‐weight their advantages.
A review of the active agents available for treatment of dentinal hypersensitivity
Authors: McFall Walter T.
Published: April 2006

Abstract Currently available for treatment of dentinal hypersensitivity are a number of active agents with various degrees of effectiveness. Some of these agents are suitable only for professional application while others can be used by individuals personally in settings outside the dental office. Mechanisms by which these active agents might modify dentin to decrease sensitivity are explored in this review. Published data on the efficacy of various agents, much of it conflicting, is critically examined. Many clinical investigations report a large placebo effect. No single agent has yet been shown to provide all of the desirable qualities of an ideal desensitizer.
Regulated cleavage of intracellular glycosylphosphatidylinositol in a trypanosome
Authors: Subramanya Sandesh , Mensa‐Wilmot Kojo
Published: April 2006

Cell exposure to hypo‐osmolarity and alkalinity triggers a spectrum of responses including activation of phospholipases. Glycosylphosphatidylinositol‐specific phospholipase C (GPI‐PLC) is expressed in Trypanosoma brucei, a protozoan parasite that causes human African trypanosomiasis. We examined possible contributions of GPI‐PLC to the response of T. brucei to hypo‐osmotic or mildly alkaline conditions. GPIs were detected at the endoplasmic reticulum (ER). They were cleaved after exposure of T. brucei to hypo‐osmolarity or mild alkalinity, which also, strikingly, caused translocation of GPI‐PLC from glycosomes (peroxisomes) to the ER. A catalytically inactive Gln81Leu mutant of GPI‐PLC failed to cleave GPIs despite being transported from glycosomes to the ER after hypo‐osmotic or mild alkaline treatment of the parasites. In contrast, a Cys347Ser mutant of the enzyme could not exit glycosomes after treatment of cells expressing the protein with mild base or hypo‐osmotic buffer. We conclude that: (a) GPI‐PLC contributes to loss of GPIs in T. brucei treated with hypo‐osmotic or mildly alkaline buffer; (b) access of GPI‐PLC to its substrate in vivo can be regulated post‐translationally; (c) translocation of GPI‐PLC from glycosomes to the ER is important for in vivo cleavage of GPIs; (d) Cys347 is part of a peptide motif required for post‐translational targeting of GPI‐PLC to the ER. Glycosome‐to‐ER movement of GPI‐PLC reveals a novel pathway for intracellular protein traffic. The physiological significance of GPI digestion in cells exposed to mildly alkalinity or hypo‐osmolarity is discussed.
Reconstitution in vitro of the GDP‐fucose biosynthetic pathways of Caenorhabditis elegans and Drosophila melanogaster
Authors: Rhomberg Simone , Fuchsluger Christina , Rendić Dubravko , Paschinger Katharina , Jantsch Verena , Kosma Paul , Wilson Iain B. H.
Published: April 2006

The deoxyhexose sugar fucose has an important fine‐tuning role in regulating the functions of glycoconjugates in disease and development in mammals. The two genetic model organisms Caenorhabditis elegans and Drosophila melanogaster also express a range of fucosylated glycans, and the nematode particularly has a number of novel forms. For the synthesis of such glycans, the formation of GDP‐fucose, which is generated from GDP‐mannose in three steps catalysed by two enzymes, is required. By homology we have identified and cloned cDNAs encoding these two proteins, GDP‐mannose dehydratase (GMD; EC 4.2.1.47) and GDP‐keto‐6‐deoxymannose 3,5‐epimerase/4‐reductase (GER or FX protein; EC 1.1.1.271), from both Caenorhabditis and Drosophila. Whereas the nematode has two genes encoding forms of GMD (gmd‐1 and gmd‐2) and one GER‐encoding gene (ger‐1), the insect has, like mammalian species, only one homologue of each (gmd and gmer). This compares to the presence of two forms of both enzymes in Arabidopsis thaliana. All corresponding cDNAs from Caenorhabditis and Drosophila, as well as the previously uncharacterized Arabidopsis GER2, were separately expressed, and the encoded proteins found to have the predicted activity. The biochemical characterization of these enzymes is complementary to strategies aimed at manipulating the expression of fucosylated glycans in these organisms.
Identification of RNase HII from psychrotrophic bacterium, Shewanella sp. SIB1 as a high‐activity type RNase H
Authors: Chon Hyongi , Tadokoro Takashi , Ohtani Naoto , Koga Yuichi , Takano Kazufumi , Kanaya Shigenori
Published: April 2006

The gene encoding RNase HII from the psychrotrophic bacterium, Shewanella sp. SIB1 was cloned, overexpressed in Escherichia coli, and the recombinant protein was purified and biochemically characterized. SIB1 RNase HII is a monomeric protein with 212 amino acid residues and shows an amino acid sequence identity of 64% to E. coli RNase HII. The enzymatic properties of SIB1 RNase HII, such as metal ion preference, pH optimum, and cleavage mode of substrate, were similar to those of E. coli RNase HII. SIB1 RNase HII was less stable than E. coli RNase HII, but the difference was marginal. The half‐lives of SIB1 and E. coli RNases HII at 30 °C were ∼ 30 and 45 min, respectively. The midpoint of the urea denaturation curve and optimum temperature of SIB1 RNase HII were lower than those of E. coli RNase HII by ∼ 0.2 m and ∼ 5 °C, respectively. However, SIB1 RNase HII was much more active than E. coli RNase HII at all temperatures studied. The specific activity of SIB1 RNase HII at 30 °C was 20 times that of E. coli RNase HII. Because SIB1 RNase HII was also much more active than SIB1 RNase HI, RNases HI and HII represent low‐ and high‐activity type RNases H, respectively, in SIB1. In contrast, RNases HI and HII represent high‐ and low‐activity type RNases H, respectively, in E. coli. We propose that bacterial cells usually contain low‐ and high‐activity type RNases H, but these types are not correlated with RNase H families.
Phylogenetic comparison and classification of laccase and related multicopper oxidase protein sequences
Authors: Hoegger Patrik J. , Kilaru Sreedhar , James Timothy Y. , Thacker Jason R. , Kües Ursula
Published: April 2006

A phylogenetic analysis of more than 350 multicopper oxidases (MCOs) from fungi, insects, plants, and bacteria provided the basis for a refined classification of this enzyme family into laccases sensu stricto (basidiomycetous and ascomycetous), insect laccases, fungal pigment MCOs, fungal ferroxidases, ascorbate oxidases, plant laccase‐like MCOs, and bilirubin oxidases. Within the largest group of enzymes, formed by the 125 basidiomycetous laccases, the gene phylogeny does not strictly follow the species phylogeny. The enzymes seem to group at least partially according to the lifestyle of the corresponding species. Analyses of the completely sequenced fungal genomes showed that the composition of MCOs in the different species can be very variable. Some species seem to encode only ferroxidases, whereas others have proteins which are distributed over up to four different functional clusters in the phylogenetic tree.
Principles of Bound Solute Dialysis
Authors: Patzer John
Published: April 2006

Abstract:  Toxins that bind to albumin in the bloodstream and are associated with progressing liver failure have proven refractory to removal by conventional hemodialysis. Such toxins can, however, be removed by adding a binder to the dialysate that serves to capture the toxin as it is dialyzed across the membrane. Several approaches based upon this concept are in various stages of clinical evaluation. The thermodynamic basis common to these approaches has been used to develop an engineering description of ‘bound solute dialysis’ which has further been used to define the clinical expectations and limitations of the approach. Three dimensionless, independently controllable, operating parameters emerged from this analysis (i): κ, the dialyzer mass transfer/blood flow rate ratio (clinical range: 0.5–2.5); (ii) α, the dialysate/blood flow rate ratio (clinical range: 0.1–2.0); and (iii) β, the dialysate/blood binder concentration ratio (clinical range: 0.02–5.0). In the absence of binder in the dialysate, bound toxin removal is sensitive to κ and α, with greater removal associated with greater κ and/or α. Bound toxin removal, however, is dependent primarily upon κ and independent of α and β once a small amount of binder, β > 0.02, is added to the dialysate. The improvement in bound toxin removal over conventional hemodialysis is dependent upon how tightly the toxin binds albumin ranging from a 6‐fold increase for a relatively tightly bound solute such as unconjugated bilirubin, to 1.5‐fold increase for a less tightly bound drug such as warfarin at 24 h perfusion time. Clinically, bound solute dialysis can be practiced in single‐pass mode with as little as 1–2 g albumin/L dialysate. Because of the constraints imposed by the thermodynamic nature of the process, intervention should be made as early in the disease progression as feasible.
How Can Liver Toxins be Removed? Filtration and Adsorption With the Prometheus System
Authors: Vienken Joerg , Christmann Horst
Published: April 2006

Abstract:  The application of extracorporeal blood circuits in liver failure therapy has its roots in the two functions of the liver, first as a detoxifying and second as a synthetizing organ. In contrast to hydrophilic uremic toxins, most liver toxins are hydrophobic and bind preferentially to blood proteins. Consequently, the majority of these compounds cannot be removed by hemodialysis or similar dialytic procedures. Current systems use albumin as a transport vehicle for hydrophobic compounds across high flux membranes (e.g. albumin‐dialysis, molecular adsorbent recirculating system (MARS)). In contrast to these devices, the Prometheus system (Fresenius Medical Care, Bad Homburg, Germany) applies filtration across highly permeable membranes with a molecular weight cut‐off of >300.000. These membranes facilitate a direct filtration of most of the toxin‐bearing proteins. In a secondary circuit these toxins are then removed by adsorber beads assembled in specially designed cartridges. The protein‐containing toxin‐free solution returns to the primary circuit. Clinical testing of the Prometheus system’s safety and efficacy parameters showed that cell counts and coagulation factors were not significantly affected. Total bilirubin‐, bile acid‐ and plasma ammonia‐levels were reduced in vivo by −21%, −43% and −40%, respectively. First successful therapeutic results have been obtained for patients treated for drug abuse and for patients waiting for transplantation. Thus, a combination of plasma fractionation with highly permeable membranes followed by a secondary circuit with adsorber cartridges proves to be the most effective method of removing toxic waste in liver failure. Further investigations will follow in order to extend the application of the Prometheus system to larger cohorts of patients.
Artificial Liver Support System in China: A Review Over the Last 30 Years
Authors: Li Lan Juan , Zhang Yi Min , Liu Xiao Li , Du Wei Bo , Huang Jian Rong , Yang Qian , Xu Xiao Wei , Chen Yue Mei
Published: April 2006

Abstract:  Severe viral hepatitis with high mortality is the most common cause of liver failure in China. Treatment of severe viral hepatitis by hemoperfusion was initially adopted in the late 1970s and early 1980s. Following 10 years of development in China, a plasma exchange (PE)‐centered artificial liver support system (ALSS), principally dependent on PE technology was developed. Based on the condition and symptoms of each patient, PE was given alone, or combined with hemodialysis, hemofiltration, hemodiafiltration, hemoperfusion, or plasma perfusion. In the late 1990s, training courses for ALSS were developed, and ALSS began to be carried out across China. Guidelines for artificial liver therapy were formulated and published by the Artificial Liver and Liver Failure Group of the Chinese Society of Infection. In recent years, new methods have been attempted, including small pore‐size plasma separators, a molecular adsorbent‐based recirculating system (MARS), and a continuous albumin purification system (CAPS). According to a retrospective analysis published in 2004, ALSS therapy significantly (P < 0.001) improved the survival rate of patients with severe hepatitis compared with patients who received only medicines (43.4%, 157/362 vs. 15.4%, 55/358 in chronic patients and 78.9%, 30/38 vs. 11.9%, 5/42 in acute and subacute patients). Furthermore, ALSS has also proved valuable as a bridge to liver transplantation in the treatment of patients with end‐stage severe hepatitis in China. More recently, ALSS has been used in the treatment of drug‐induced liver failure, acute fatty liver during pregnancy, and other difficult‐to‐treat disorders in China.
Bioartificial Liver: Its Pros and Cons
Authors: Chamuleau Robert AFM , Poyck Paul PC , Van De Kerkhove Maarten‐Paul
Published: April 2006

Abstract:  Both the large variety of liver functions for maintaining body homeostasis and the proven effectivity of whole liver transplantation in the therapy of acute liver failure (ALF), are important reasons to presume that cell‐free liver support systems will not be able to adequately support the failing liver. Accordingly, bioartificial liver (BAL) systems have shown their efficacy in experimental ALF models in small and large animals, and have shown to be suitable and safe in phase 1 studies in humans with ALF. However, the optimal BAL system is still under development. Important issues are the source of the cellular component and the configuration of the BAL system with regard to cell attachment, mass transfer characteristics and oxygenation at site. The deficiency of all BAL systems to excrete bile effectively is another important topic for improvement. The great challenge for the future is to develop a well‐functioning and safe human hepatic cell line which can replace the widely used porcine (xenogeneic) hepatocytes. Theoretically, a combination of a cell‐free liver support system and a BAL system might be optimal for the treatment of ALF patients in the near future.
rHuG‐CSF Increases the Platelet‐Neutrophil Complex Formation and Neutrophil Adhesion Molecule Expression in Volunteer Granulocyte and Stem Cell Apheresis Donors
Authors: Karadogan Cavidan , Karadogan Ihsan , Bilgin Aynur Ugur , Undar Levent
Published: April 2006

Abstract:  Several reports have shown that granulocyte colony‐stimulating factor (G‐CSF) administration induces a transient, mild hypercoagulable state, which might predispose certain donors to thrombotic complications. In the present study, changes in the expression of neutrophil adhesion molecules (CD11b/CD18, CD62L) and platelet‐neutrophil complex formation following rHuG‐CSF administration were investigated in normal granulocyte and stem cell donors. For granulocyte apheresis (N = 10), rHuG‐CSF (5 µg/kg) was given subcutaneously every 12 h three times and apheresis was carried out two hours after the last dose. For stem cell apheresis (N = 8), rHuG‐CSF (10 µg/kg/day) was given subcutaneously for 5 days and apheresis was carried out when peripheral CD34+ cell counts exceeded 20 cell/µL. Expression of neutrophil adhesion molecules (CD11b/CD18, CD62L) and platelet‐neutrophil complex formation following rHuG‐CSF administration were investigated in donors by a flow cytometric method. A significant increase in neutrophil counts (P < 0.001), and decreases in platelet counts (P < 0.01) and hemoglobin levels (P < 0.01) occurred following G‐CSF administration. The expression of CD11b/CD18 significantly increased (P < 0.001) over pretreatment values with G‐CSF administration and returned to baseline 1 week after stopping the drug. In contrast, CD62L expression was decreased (P < 0.01) with G‐CSF and returned to normal after cessation of the drug. rHuG‐CSF caused more than a two‐fold increase (from 0.3 to 7.0 × 109/L) in circulating platelet‐neutrophil complexes (P < 0.01), which returned to normal after 1 week. Although clinical significance of these laboratory changes is not clear, the occurrence of neutrophil activation and increased platelet‐neutrophil complex formation might predispose certain donors or patients to thrombotic complications following G‐CSF administration.
Prevalence of Hepatitis E Virus Infection in Regular Hemodialysis Patients
Authors: Kikuchi Kan , Yoshida Takumi , Kimata Naoki , Sato Chifumi , Akiba Takashi
Published: April 2006

Abstract:  The percentage of patients infected with blood‐borne diseases, including hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, is high in patients undergoing hemodialysis regularly. Hepatitis E virus (HEV) is transmitted via the fecal‐oral route, and blood‐borne HEV infection has also been reported recently. On the basis of these findings, we investigated the actual status of HEV infection in regular hemodialysis patients. Out of 1077 patients undergoing hemodialysis at two key hospitals and three outpatient hemodialysis clinics, 300 were randomly selected as the subjects. Among these 300 hemodialysis patients, 19.0% were IgG‐type anti‐HEV antibody‐positive. The percentage of HEV‐infected patients increased with patient age and it was particularly high in patients 40 years of age or older. The percent IgG‐type anti‐HEV antibody positivity was not significantly different (P = 0.14) between anti‐HCV antibody‐positive patients (27.8%) and anti‐HCV antibody‐negative patients (17.8%). The percentage of HEV‐infected patients among the hemodialysis patients was higher than that previously reported among patients with healthy kidneys. No correlation was observed between the percentage of HEV‐infected patients and HCV infection incidence or a history of blood transfusion. The percent IgG‐type anti‐HEV antibody positivities were significantly different among the facilities. It was impossible to specify the route of infection, and the correlation between the incidence of infection and hemodialysis therapy was not clear. Because more routes of infection are possible for patients undergoing dialysis than for persons with normal kidney function, it seems necessary to analyze the significance of infection incidence, the route of infection and infection prevention measures.
The General Circulation of the Atmosphere
Authors: Schneider Tapio
Published: April 2006

Theories of how Earth's surface climate may change in the future, of how it may have been in the past, and of how it is related to climates of other planets must build upon a theory of the general circulation of the atmosphere. The view of the atmospheric general circulation presented here focuses not on Earth's general circulation as such but on a continuum of idealized circulations with axisymmetric flow statistics. Analyses of observational data for Earth's atmosphere, simulations with idealized general circulation models, and theoretical considerations suggest how characteristics of the tropical Hadley circulation, of the extratropical circulation, and of atmospheric macroturbulence may depend on parameters such as the planet radius and rotation rate and the strength of the differential heating at the surface.
Continuous flow augments reactivity of rabbit carotid artery by reducing bioavailability of NO despite an increase in release of EDHF
Authors: Rasmussen Lasse E. , Vanhoutte Paul M. , Jensen Boye L. , Skøtt Ole
Published: April 2006

Experiments were designed to investigate the influence of steady flow and pressure on endothelial function in the rabbit carotid artery. Increases and decreases in isometric force were compared in static rings and perfused (5 or 50 ml/min) segments of the same arteries in the presence and absence of endothelium. The α1-adrenoceptor agonist phenylephrine and the muscarinic agonist acetylcholine were applied as vasoconstrictor and vasodilator stimuli, respectively. Continuous flow (5 and 50 ml/min) reduced the cGMP content and shifted the concentration-response curve to phenylephrine to the left compared with nonperfused static rings. Removal of the endothelium abolished the differences in cGMP content and the sensitivity to phenylephrine between static rings and perfused segments. No difference in sensitivity to phenylephrine was observed in tissues treated with Nω-nitro-l-arginine methyl ester (l-NAME). Acetylcholine-evoked relaxations were increased in perfused segments. l-NAME nearly abolished the acetylcholine-evoked relaxation in static rings, whereas about one-half of the relaxation remained in segments exposed to flow. This remnant relaxation was blocked by inhibition of endothelial small- and intermediate-conductance calcium-activated potassium channels by apamin plus 1-[(2-chlorophenyl)diphenylmethyl]-1 H-pyrazole (TRAM-34). These experiments demonstrate that continuous flow increases the constriction evoked by α1-adrenergic activation in the rabbit carotid artery through a reduced influence of basally released endothelial NO and, furthermore, that luminal flow unmasks an ability of the endothelium to release a non-NO, noncyclooxygenase vasodilator, presumably endothelium-derived hyperpolarizing factor.
Cardioprotective role of endogenous hydrogen peroxide during ischemia-reperfusion injury in canine coronary microcirculation in vivo
Authors: Yada Toyotaka , Shimokawa Hiroaki , Hiramatsu Osamu , Haruna Yoshisuke , Morita Yoshitaka , Kashihara Naoki , Shinozaki Yoshiro , Mori Hidezo , Goto Masami , Ogasawara Yasuo , Kajiya Fumihiko
Published: April 2006

We have recently demonstrated that endogenous H2O2 plays an important role in coronary autoregulation in vivo. However, the role of H2O2 during coronary ischemia-reperfusion (I/R) injury remains to be examined. In this study, we examined whether endogenous H2O2 also plays a protective role in coronary I/R injury in dogs in vivo. Canine subepicardial small coronary arteries (≥100 μm) and arterioles (<100 μm) were continuously observed by an intravital microscope during coronary I/R (90/60 min) under cyclooxygenase blockade ( n = 50). Coronary vascular responses to endothelium-dependent vasodilators (ACh) were examined before and after I/R under the following seven conditions: control, nitric oxide (NO) synthase (NOS) inhibitor NG-monomethyl-l-arginine (l-NMMA), catalase (a decomposer of H2O2), 8-sulfophenyltheophylline (8-SPT, an adenosine receptor blocker), l-NMMA + catalase, l-NMMA + tetraethylammonium (TEA, an inhibitor of large-conductance Ca2+-sensitive potassium channels), and l-NMMA + catalase + 8-SPT. Coronary I/R significantly impaired the coronary vasodilatation to ACh in both sized arteries (both P < 0.01); l-NMMA reduced the small arterial vasodilatation (both P < 0.01), whereas it increased ( P < 0.05) the ACh-induced coronary arteriolar vasodilatation associated with fluorescent H2O2 production after I/R. Catalase increased the small arterial vasodilatation ( P < 0.01) associated with fluorescent NO production and increased endothelial NOS expression, whereas it decreased the arteriolar response after I/R ( P < 0.01). l-NMMA + catalase, l-NMMA + TEA, or l-NMMA + catalase + 8-SPT further decreased the coronary vasodilatation in both sized arteries (both, P < 0.01). l-NMMA + catalase, l-NMMA + TEA, and l-NMMA + catalase + 8-SPT significantly increased myocardial infarct area compared with the other four groups (control, l-NMMA, catalase, and 8-SPT; all, P < 0.01). These results indicate that endogenous H2O2, in cooperation with NO, plays an important cardioprotective role in coronary I/R injury in vivo.
Preconditioning by 17β-estradiol in isolated rat heart depends on PI3-K/PKB pathway, PKC, and ROS
Authors: Sovershaev Mikhail A. , Egorina Elena M. , Andreasen Thomas V. , Jonassen Anne K. , Ytrehus Kirsti
Published: April 2006

To study the cell signaling events leading to 17β-estradiol (E2)-induced acute cardioprotection, we subjected isolated rat hearts to three 5-min cycles of 10 μM E2 before 30 min of regional ischemia, followed by 2 h of reperfusion. Protection was judged by changes in infarct size in percentage of risk zone volume. To test the importance of phosphoinositide 3-kinase (PI3-K), protein kinase C (PKC), or reactive oxygen species (ROS) in E2-induced protection, we combined wortmannin (1 μM), chelerythrine (2 μM), and 2-mercaptopropionylglycine (300 μM), respectively, with E2 exposure. Changes in phosphorylation of protein kinase B (PKB) and selected PKC isoforms were tested by immunoblotting of total lysates and subcellular fractions, along with assessment of PKC translocation from soluble to membrane fraction of heart tissue homogenates. Intracellular ROS levels induced by E2 preconditioning were investigated. E2 preconditioning led to significant reduction in infarct size from 31.8 ± 5.3 to 20.2 ± 2.6% in male hearts and from 42.7 ± 4.7 to 17.1 ± 3.4% in female hearts ( P < 0.05). Protection was abolished by wortmannin (30.0 ± 3.2%), chelerythrine (45.1 ± 4.4%), and 2-mercaptopropionylglycine (36.8 ± 4.7%). E2 preconditioning induced phosphorylation of PKB, PKCα, and PKCε and membrane translocation of PKCε and PKCδ. Intracellular ROS levels were found elevated after transient treatment with hormone. Therefore, our data demonstrate the ability of E2 to induce preconditioning-like cardioprotection via cell signaling events shared by classic ischemic preconditioning.
Differential modulation of Kv4.2 and Kv4.3 channels by calmodulin-dependent protein kinase II in rat cardiac myocytes
Authors: Colinas Olaia , Gallego Mónica , Setién Raúl , López-López José Ramón , Pérez-García M. Teresa , Casis Oscar
Published: April 2006

In this work we have combined biochemical and electrophysiological approaches to explore the modulation of rat ventricular transient outward K+current ( Ito) by calmodulin kinase II (CaMKII). Intracellular application of CaMKII inhibitors KN93, calmidazolium, and autocamtide-2-related inhibitory peptide II (ARIP-II) accelerated the inactivation of Ito, even at low [Ca2+]. In the same conditions, CaMKII coimmunoprecipitated with Kv4.3 channels, suggesting that phosphorylation of Kv4.3 channels modulate inactivation of Ito. Because channels underlying Itoare heteromultimers of Kv4.2 and Kv4.3, we have explored the effect of CaMKII on human embryonic kidney (HEK) cells transfected with either of those Kvα-subunits. Whereas Kv4.3 inactivated faster upon inhibition of CaMKII, Kv4.2 inactivation was insensitive to CaMKII inhibitors. However, Kv4.2 inactivation became slower when high Ca2+was used in the pipette or when intracellular [Ca2+] ([Ca2+]i) was transiently increased. This effect was inhibited by KN93, and Western blot analysis demonstrated Ca2+-dependent phosphorylation of Kv4.2 channels. On the contrary, CaMKII coimmunoprecipitated with Kv4.3 channels without a previous Ca2+increase, and the association was inhibited by KN93. These results suggest that both channels underlying Itoare substrates of CaMKII, although with different sensitivities; Kv4.2 remain unphosphorylated unless [Ca2+]iincreases, whereas Kv4.3 are phosphorylated at rest. In addition to the functional impact that phosphorylation of Kv4 channels could cause on the shape of action potential, association of CaMKII with Kv4.3 provides a new role of Kv4.3 subunits as molecular scaffolds for concentrating CaMKII in the membrane, allowing Ca2+-dependent modulation by this enzyme of the associated Kv4.2 channels.