bluuebunny/crossref_metadata_2025 huggingface dataset:
Marginal fit of cemented and screw‐retained crowns incorporated on the Straumann (ITI)® Dental Implant System: an in vitro study
Authors: Tosches N. A. , Brägger U. , Lang N. P.
Published: January 2009

Aim: The aim of this study was to assess the marginal fit of crowns on the Straumann (ITI)® Dental Implant System with special consideration of different casting dental materials.

Material and methods: Sixty porcelain‐fused‐to‐metal crowns were fabricated: 18 crowns on standard cone abutments with an impression cylinder, partially prefabricated analogs, no coping and screw‐retained (A); 18 crowns on solid abutments without an impression device, no analogs, no coping and cemented (B); and 18 crowns on solid abutments using an impression transfer cap, an analog with a shoulder, no coping and cemented (C). In each group, six crowns were made on epoxy mastercasts (Bluestar®), six on synthetic plaster (Moldasynt®) and six on super hard stone (Fujirock®). Six additional crowns were fabricated with the transversal screw retention system onto the Octa® system with impression transfer caps, metal analogs, gold copings and screw‐retained (D). Impregum® was used as impression material. Crowns of B and C were cemented with KetacCem®. Crowns of A and D were fixed with an occlusal screw torqued at 15 N cm. Crowns were embedded, cut and polished. Under a light microscope using a magnification of × 100, the distance between the crown margin (CM) and the shoulder (marginal gap, MG) and the distance between the CM and the end of the shoulder (crown length, CL) was measured.

Results: MGs were 15.4±13.2 μm (A), 21.2±23.1 μm (B), 11±12.1 μm (C) and 10.4±9.3 μm (D). No statistically significantly differences using either of the casting materials were observed. CLs were −21.3±24.8 μm (A), 3±28.9 μm (B), 0.5±22 μm (C) and 0.1±15.8 μm (D). Crowns were shorter on synthetic casting materials compared with stone casts (P<0.005).

Conclusions: CMs fit precisely with both cemented and screw‐retained versions as well as when using no, partial or full analogs.
Bone quality in the midpalate for temporary anchorage devices
Authors: Wehrbein Heinrich
Published: January 2009

Objective: The aim of the present study was to quantitatively assess the bone quality of the palatal bone from an implantologic standpoint.

Material and methods: The material consisted of palatal tissue blocks of autopsy material from 22 subjects (19 male, three female), between 18 and 63 years of age. The specimens comprised the anterior part of median palate (APMP) from about 7 mm behind the incisive foramen (first premolar regions), the middle part of median palate (MPMP, second premolar region), and the posterior part of the median palate (PPMP, first molar region). They were prepared in the transversal plane using ground‐thin‐section technology. The midpalatal areas of the different parts of the palate [regions of interest (ROI) for temporary anchorage device (TAD) placement] 3 mm bilaterally to the midline were assessed with respect to hard tissue fraction to total bone volume (HTF/TBV), bone marrow fraction to total bone volume (BMF/TBV), and sutural tissue fraction to total bone volume (STF/TBV). Furthermore, age‐specific evaluation was performed: younger age group (18–25 years, n=10) and older age group (26–63 years, n=12).

Results: Histomorphometric measurement showed the following results for the APMP: mean HTF/TBV, 68.57%; mean BMF/TBV, 21.38%; and mean STF/TBV, 9.96%. There were no statistically significant differences between the various tissue fractions of the APMP, MPMP, and PPMP. The younger age group showed a mean HTF/TBV of 68.88%, a mean BMF/TBV of 21.5%, and a mean STF/TBV of 9.53%. No statistically significant differences with the older age group were found.

Conclusion: These results suggest that the HTF in the APMP, MPMP, and PPMP in younger as well as older adults is relatively high. Thus, good primary stability of TADs should be achieved in all parts of the adult median palate independent of age.
Bleeding on probing and pocket probing depth in relation to probing pressure and mucosal health around oral implants
Authors: Gerber J. A. , Tan W. C. , Balmer T. E. , Salvi G. E. , Lang N. P.
Published: January 2009

Objectives: To assess the bleeding on probing (BOP) tendency and periodontal probe penetration when applying various probing forces at implant sites in patients with a high standard of oral hygiene with well‐maintained peri‐implant tissues.

Material and methods: Seventeen healthy patients with excellent oral hygiene in a maintenance program after having been treated for periodontitis or gingivitis were recruited. Missing teeth had been replaced using oral implants. The BOP and probing depth (PPD) were assessed at the mid‐buccal, mid‐oral, mesial and distal aspects of the buccal surfaces of each implant. Moreover, contralateral teeth were designated and assessed for BOP and PPD in the same locations and at the same observation visits. At each visit, implants and contralateral teeth were randomly assigned to one of the standardized probing forces (0.15 or 0.25 N). The second probing force was applied at the repetition of the examination 7 days later.

Results: Increasing the probing pressure by 0.1 N from 0.15 N resulted in an increase of BOP percentage by 13.7% and 6.6% for implants and contralateral teeth, respectively. There appeared to be a significant difference of the mean BOP percentage at implant and tooth sites when a probing pressure of 0.25 N was applied. A significantly deeper mean PPD at implant sites compared with tooth sites was found irrespective of the probing pressure applied.

Conclusions: The results of the present study demonstrated that 0.15 N might represent the threshold pressure to be applied to avoid false positive BOP readings around oral implants. Hence, probing around implants demonstrated a higher sensitivity compared with probing around teeth.
Effect of modifications of dual acid‐etched implant surfaces on peri‐implant bone formation. Part I: organic coatings
Authors: Schliephake H. , Aref A. , Scharnweber D. , Bierbaum S. , Sewing A.
Published: January 2009

Objective: The aim of the present study was to test the hypothesis that peri‐implant bone formation can be improved by modifying dual acid‐etched (DAE) implant surfaces using organic coatings that enhance cell adhesion and osteogenic differentiation.

Material and methods: Ten adult female foxhounds received experimental titanium implants in the mandible 3 months after removal of all premolar teeth. Six types of implants were evaluated in each animal: (i) implants with a machined surface (MS), (ii) implants with a DAE surface topography, (iii) implants with an acid‐etched surface coated with RGD peptides, (iv) implants with an acid‐etched surface coated with collagen I, (v) implants with an acid‐etched surface coated with collagen I and chondroitin sulphate (CS), (vi) implants with an acid‐etched surface coated with collagen I and CS and recombinant human bone morphogenetic protein‐2. Peri‐implant bone regeneration was assessed by histomorphometry after 1 and 3 months in five dogs each by measuring bone implant contact (BIC) and the bone volume density (BVD) of the newly formed peri‐implant bone.

Results: After 1 month, mean BIC was significantly higher in the coated implants group than in the MS group. There was no significant difference when mean BIC in the DAE group was compared with implants with any of the organic coatings, but the difference was significant when compared with the MS implants. Differences in mean BVD value did not reach significance between any of the surfaces. After 3 months, the same held true for the mean BIC of all the groups except for Coll I. Mean volume density of the newly formed bone was higher in all the surface modifications, albeit without statistical significance.

Conclusions: It is concluded that with the exception of Coll I, the tested organic surface coatings on DAE surfaces did not improve peri‐implant bone formation when compared with the DAE surfaces but enhanced BIC when compared with the MSs.
Evaluation of a new biodegradable membrane to prevent gingival ingrowth into mandibular bone defects in minipigs
Authors: Thoma Daniel S. , Halg Gian‐Andrea , Dard Michel M. , Seibl Reinhart , Hammerle Christoph H. F. , Jung Ronald E.
Published: January 2009

Objective: The aim of this study was to test whether a synthetic, biodegradable membrane made of polyethylene glycol (PEG) can prevent soft‐tissue ingrowth into alveolar defects.

Material and methods: In each of 16 minipigs, three mandibular premolars were bilaterally extracted. Three months later, acute standardized defects (diameter 8 mm, depth 8 mm) were prepared. Four treatment modalities were randomly allocated to the defects: (1) PEG membrane plus collagen sponge, (2) polylactide (PLA) membrane plus collagen sponge, (3) collagen sponge alone, and (4) empty defect. Animals were sacrificed at 10 days (n=5), 21 days (n=5), or 2 months (n=6) after treatment. Qualitative and quantitative histological evaluations of soft‐tissue ingrowth and bone regeneration were performed on nondecalcified ground sections. For statistical analysis, the Mann–Whitney–Wilcoxon test, the Kruskal–Wallis, and the paired t‐test were applied. P‐values were adjusted using the Dunnett–Hsu adjustment.

Results: At 10 days, the PEG membrane group showed the least soft‐tissue ingrowth (mean value −0.75 mm; range −1.35 to −0.10), followed by the PLA membrane group −0.18 mm (−0.80 to 0.44), the collagen group 0.04 mm (−0.65 to 0.73), and the empty defects 0.60 mm (−0.08 to 1.29). Statistically significant differences were observed between the PEG membrane group and the empty defects (P<0.05). At 21 days, the highest percentage of newly formed bone was found in the PEG membrane group (mean 28.4%; range 21.6–35.2) compared with 23.7% (16.9–30.5; PLA membrane), 15.2% (8.2–22.2; collagen group), and 21.6% (14.5–28.8; empty defects). Statistically significant differences were only found between the PEG membrane group and the collagen group (P<0.05). At 2 months, the tested parameters revealed no statistically significant differences between the groups.

Conclusion: The experimental PEG membrane applied in the present study successfully prevented collapse of the covering soft tissues to a degree similar to the PLA membrane. The combination of a collagen sponge and the PEG membrane showed the least soft‐tissue ingrowth at 10 days and promoted more bone formation at 21 days.
Pore characteristics of bone substitute materials assessed by microcomputed tomography
Authors: Klein Marcus , Goetz Hermann , Pazen Sabine , Al‐Nawas Bilal , Wagner Wilfried , Duschner Heinz
Published: January 2009

Objectives: Pore configurations of alloplastic biomaterial scaffolds play a major role for new bone formation in vivo. Current studies on characteristics of pores in bone substitute materials focus on individual particles or single blocks. Thus, three‐dimensional (3‐D) architecture of particle aggregates, representing the clinical relevant in vivo situation is not adequately taken into account. The aim of this study was the visualization and quantification of pore properties, both of the scaffold structure of single particles as well as of the micro‐morphology of complex 3‐D aggregated particle‐conglomerates.

Material and methods: In model experiments, standardized plexiglass cylinders were stuffed with commercial bone substitute material particles with diverse chemical composition (HA, β‐TCP, HA‐SiO2, HA‐β‐TCP, bioactive glass), origin (phycogenic, bovine, synthetic) and granulation (50 μm–2000 μm). Analogue to establish procedures for native (human) bone samples, non‐fixed bone substitute materials were scanned by high‐resolution microcomputed tomography. In addition to computer animated two‐dimensional and 3‐D reconstruction of the samples, median pore thickness and pore size distribution were determined. Materials representative for their chemical constitution were documented by SEM imaging.

Results: Investigated specimens significantly were different in micro‐morophology and pore properties, ranging from highly porous to rather solid. The most voluminous pores were localized interparticularly. Within one product line, the determined pore properties showed a significant correlation with single particle grain sizes.

Conclusion: The generation and interpretation of μ‐CT based 3‐D pore models can provide further insight into the expected osteoconduction dynamics and therefore might serve as a basis for further modifications of scaffold size and geometry as well as for further invasive studies on the biological behaviour of the scaffolds.
Human osteoclast formation and activity on an equine spongy bone substitute
Authors: Perrotti Vittoria , Nicholls Brian M. , Piattelli Adriano
Published: January 2009

Objectives: The aim of the present study was to evaluate the in vitro formation and activity of human osteoclasts (OCLs) generated on a new type of xenograft for bone substitution, an equine spongy bone.

Material and methods: Peripheral blood mononuclear cells from healthy volunteers were used to generate OCLs in vitro in the presence of macrophage colony stimulating factor (M‐CSF) and receptor activator of NF‐κB ligand (RANKL) on bovine bone slices (positive control) and equine spongy bone. Morphological and biochemical methods were used to assess OCLs formation and activity.

Results: Cells generated after 21 days of culture on equine spongy bone showed similar morphology to those on the positive control and displayed typical OCL markers and features, indicating that this material supported OCL formation. Moreover, these cells were functionally active on equine spongy bone with statistically significant differences compared with the control in the release of tartrate‐resistant acid phosphatase (TRAcP5b) at days 14 and 21 of culture. With regard to the resorption, on equine bone, OCLs formed smaller discontinuous island‐like lacunae rather than the typical lobulated, tracking resorption lacunae observed on the control.

Conclusions: This study enables clinicians to tailor the usage of equine spongy bone and presents a model, which can be applied to the preclinical assessment of bone substitute material's resorbability and resorption rates.
Ectopic bone formation after implantation of a slow release system of polylactid acid and rhBMP‐2
Authors: Gruber R. , Weich H.A. , Dullin C. , Schliephake H.
Published: January 2009

Objectives: The present study was conducted to test the hypothesis that preshaped polylactic acid (PLA) implants loaded with recombinant human bone morphogenic protein 2 (rhBMP‐2) can induce bone formation in a rat ectopic model.

Materials and methods: Two groups of porous cylindrical poly‐dl‐lactic acid implants of 8‐mm diameter were produced by gas foaming with CO2, incorporating 48 and 96 μg rhBMP‐2, respectively, into each implant. Blank PLA implants were used as controls. The release of BMPs and the induction of alkaline phosphatase were assessed in vitro. Osteoinduction in vivo was tested by insertion of 15 implants from each group into the gluteal muscles of Wistar rats. Five implants from each group were retrieved after 6, 13 and 26 weeks and assessed using flat panel volume detector computed tomography and light microscopy.

Results: Both groups of implants showed increased release of rhBMP‐2 during the first 24–48 h, with a slightly higher amount being released from the implants with 48 μg. Release during subsequent intervals was <100 ng/72 h in the low‐concentration group and >100 ng in the group with 96 μg rhBMP‐2. Implants with 95 μg rhBMP‐2 exhibited bone formation in vivo on the outside of the implants across the observation period of 26 weeks with invasion of bone into the pores, whereas implants with 48 μg rhBMP‐2 failed to induce the formation of bone tissue. No bone formation was found in the control implants.

Conclusions: The results suggest that release rates of rhBMP‐2 for ectopic bone induction have to be >100 ng/72 h to maintain the osteoinductive activity of the tested porous PLA implants. This slow release system may have impact on alveolar bone augmentation procedures when used as individually preformed osteoinductive implants.
Short‐term clinical and microbiological evaluations of peri‐implant diseases before and after mechanical anti‐infective therapies
Authors: Máximo Maria Beatriz , De Mendonça Adriana Cutrim , Renata Santos Vanessa , Figueiredo Luciene Cristina , Feres Magda , Duarte Poliana Mendes
Published: January 2009

Objectives:The aim of this study was to evaluate the clinical and microbiological effects of mechanical anti‐infective therapies for mucositis and peri‐implantitis.

Material and methods:Subjects with at least one dental implant were assigned to healthy (n=10), mucositis (n=12) or peri‐implantitis (n=13) groups. Implants with mucositis or peri‐implantitis were decontaminated by means of teflon curettes and abrasive sodium carbonate air‐powder, performed by an open flap for peri‐implantitis and without surgery for mucositis. Visible plaque (PI), marginal bleeding (MB), bleeding on probing (BOP), suppuration (SUP), probing depth (PD) and relative clinical attachment level (rCAL) were assessed at baseline and at 3 months after therapies. At the same time points, submucosal plaque samples were collected from each implant and analyzed by Checkerboard DNA–DNA hybridization for 40 bacterial species.

Results:All clinical parameters improved at 3 months post‐therapy in mucositis and peri‐implantitis groups (P<0.05). The mean reduction in rCAL (±SD) was 1.4±1.2 mm and 2.3±1.6 mm, and it was 1.3±1.2 mm and 3.1±1.7 mm in PD (±SD) for mucositis and peri‐implantitis, respectively. Levels ofTreponema denticola, Tanerella forsythiaandParvimonas micra, and ofFusobacterium nucleatum ss nucleatum, were significantly reduced after peri‐implantitis therapy and after mucositis therapy, respectively (P<0.05). In addition, counts ofPorphyromons gingivalis, Treponema socranskiiand the proportions of red complex were reduced in both groups at 3 months after treatments (P<0.05).

Conclusion:Mechanical therapies alone were effective in treating mucositis and peri‐implantitis over a period of 3 months. The open debridement procedure showed clinical and microbiological benefits on the treatment of peri‐implantitis and could be safely used as a standard control group for future studies.
Bif‐1 and Bax expression in cutaneous Merkel cell carcinoma
Authors: Schlauder Scott M. , Calder Kenneth B. , Khalil Farah K. , Passmore Leslie , Mathew Rahel A. , Morgan Michael B.
Published: January 2009

Background:  Bax‐interacting factor‐1 (Bif‐1) binds to Bax, which in turn activates this proapoptotic protein. In the absence of Bif‐1, the ability to induce apoptosis through the intrinsic pathway is greatly reduced. Merkel cell carcinoma (MCC) classically shows an aggressive behavior and lack of response to chemotherapy, which remains unexplained. Previous studies have documented the presence of Bax in MCC, but Bif‐1 expression has not been evaluated. Herein, the expression of Bif‐1 and Bax in cutaneous MCC is examined.

Materials and methods:  The immunohistochemical expression of Bif‐1 and Bax protein was examined in nine cases of MCC. Both positive and negative controls were conducted. All the cases were reviewed by a single dermatopathologist.

Results:  Bif‐1 was detected in nine cases (100%), and Bax was expressed in six cases (66%). The percent positive cells for Bif‐1 in MCC ranged from 85% to 98% positive (mean 93.9%). At the same time, decreased Bax expression was shown with 0–8% positive cells (mean 3.45%).

Conclusion:  The increased expression of Bif‐1 in MCC is associated with low levels of Bax staining. These findings suggest that the upregulation of Bif‐1 could in part be responsible for tumorigenesis in cutaneous MCC. As shown, Bax and Bif‐1 expression are not exclusively antithetical; therefore, future studies evaluating the expression of both proteins should be conducted.
Rhabdomyomatous mesenchymal hamartoma presenting on a digit
Authors: Brinster Nooshin K. , Farmer Evan R.
Published: January 2009

Rhabdomyomatous mesenchymal hamartoma is a rare dermal lesion comprised of skeletal muscle, adipocytes and collagen. The vast majority has been described in very young patients on the head and neck. To our knowledge, there are only two reports of rhabdomyomatous mesenchymal hamartoma outside the head and neck region. Both of those lesions were located in the perianal area. We describe a rhabdomyomatous mesenchymal hamartoma in a 36‐year‐old man located on the great toe. Although rhabdomyomatous mesenchymal hamartoma is uncommon, it is important to be aware of this entity, its possible association with congenital syndromes and its potential for localization outside of the head and neck region.
Free iron, total F2‐isoprostanes and total F4‐neuroprostanes in a model of neonatal hypoxic–ischemic encephalopathy: neuroprotective effect of melatonin
Authors: Signorini Cinzia , Ciccoli Lucia , Leoncini Silvia , Carloni Silvia , Perrone Serafina , Comporti Mario , Balduini Walter , Buonocore Giuseppe
Published: January 2009

Abstract:   Oxidative stress due to free radical formation and initiation of abnormal oxidative reactions is involved in several diseases of newborns, such as hypoxic–ischemic encephalopathy. Melatonin, an endogenously produced indoleamine primarily formed in the pineal gland, is a potent free radical scavenger as well as an indirect antioxidant. The present study was conducted to evaluate the formation of oxidative damage mediators and the possible effect of melatonin treatment in a model of hypoxic–ischemic encephalopathy in 7‐day‐old rats. Pups were subjected to permanent ligation of the right common carotid artery and exposed for 2.5 hr to a nitrogen–oxygen mixture (92% and 8%, respectively) (hypoxia–ischemia, HI). Melatonin was injected intraperitoneally to a group of rats at the dose of 15 mg/kg 30 min before starting the ischemic procedure (HI–Melatonin). After 24 hr of treatment, in homogenized cerebral cortex, desferoxamine (DFO)‐chelatable free iron, total F2‐isoprostanes and total F4‐neuroprostanes, originating from the free radical‐catalyzed peroxidation of arachidonic and docosahexaenoic acids, respectively, were determined. HI induced a significant increase in DFO‐chelatable iron, total F2‐isoprostanes and F4‐neuroprostanes in both right and left side of the cerebral cortex. In HI–Melatonin‐treated animals the levels of free iron, F2‐isoprostanes, and F4‐neuroprostanes were significantly lower than that in HI rats and the values were similar to controls. These data show the important neuroprotective role of melatonin in reducing oxidative damage resulting from HI. Melatonin could represent a potential safe approach to perinatal brain damage in humans.
Protective effects of melatonin against oxidative stress in Fmr1 knockout mice: a therapeutic research model for the fragile X syndrome
Authors: Romero‐Zerbo Yanina , Decara Juan , El Bekay Rajaa , Sanchez‐Salido Lourdes , Del Arco‐Herrera Ignacio , De Fonseca Fernando Rodríguez , De Diego‐Otero Yolanda
Published: January 2009

Abstract:  Fragile X syndrome is the most common form of inherited mental retardation. It is typically caused by a mutation of the Fragile X mental‐retardation 1 (Fmr1) gene. To better understand the role of the Fmr1 gene and its gene product, the fragile X mental‐retardation protein in central nervous system functions, an fmr1 knockout mouse that is deficient in the fragile X mental‐retardation protein was bred. In the present study, fragile X mental retardation 1‐knockout and wild‐type mice are used to determine behaviour and oxidative stress alterations, including reduced glutathione, oxidized glutathione and thiobarbituric acid‐reactive substances, before and after chronic treatment with melatonin or tianeptine. Reduced glutathione levels were reduced in the brain of fmr1‐knockout mice and chronic melatonin treatment normalized the glutathione levels compared with the control group. Lipid peroxidation was elevated in brain and testes of fmr1‐knockout mice and chronic melatonin treatment prevents lipid peroxidation in both tissues. Interestingly, chronic treatment with melatonin alleviated the altered parameters in the fmr1‐knockout mice, including abnormal context‐dependent exploratory and anxiety behaviours and learning abnormalities. Chronic treatment with tianeptine (a serotonin reuptake enhancer) did not normalize the behaviour in fmr1‐knockout mice. The prevention of oxidative stress in the fragile X mouse model, by an antioxidant compound such as melatonin, emerges as a new and promising approach for further investigation on treatment trials for the disease.
N‐Nitrosomelatonin: synthesis, chemical properties, potential prodrug
Authors: Kirsch Michael , De Groot Herbert
Published: January 2009

Abstract: Melatonin is easily nitrosated via various mechanisms at the nitrogen atom of the indole ring to giveN‐nitrosomelatonin (NOMela). This Mini‐review provides a comprehensive view of thisN‐nitroso compound. With an improved procedure NOMela can now economically synthesized with low laboratory expenditure. The major chemical property of NOMela, i.e. the (formally) transfer of the NO+function to its target nucleophile, is explained in detail and a variety of detection methods using this reaction are suggested. As the suspected carcinogenical potential of NOMela is clearly overruled it seems attractive to apply this nitroso compound for endogenous generation ofS‐nitrosothiols that act as nitric oxide donors in vivo.
Phe27Cys Polymorphism Alters the Maturation and Subcellular Localization of the Human δ Opioid Receptor
Authors: Leskelä Tarja T. , Markkanen Piia M. H. , Alahuhta Ilkka A. , Tuusa Jussi T. , Petäjä‐Repo Ulla E.
Published: January 2009

The human δ opioid receptor (hδOR) is a G‐protein‐coupled receptor that is mainly involved in the modulation of pain and mood. Only one nonsynonymous single nucleotide polymorphism (T80G) has been described, causing Phe27Cys substitution in the receptor N‐terminus and showing association with substance dependence. In this study, we expressed the two hδOR variants in a heterologous expression system with an identical genetic background. They differed greatly during early steps of biosynthesis, displaying a significant difference in the maturation efficiency (50% and 85% for the Cys27 and Phe27 variants, respectively). The Cys27 variant also showed accumulation in pre‐Golgi compartments of the secretory pathway and impaired targeting to endoplasmic reticulum (ER)‐associated degradation following long‐term expression. In addition, the cell surface receptors of the Cys27 variant internalized constitutively. Replacement of phenylalanine with other amino acids revealed that cysteine at position 27 decreased the mature receptor/precursor ratio most extensively, suggesting a thiol‐mediated retention of precursors in the ER. However, cysteine did not cause a major folding defect because pharmacological characteristics and the maturation kinetics of the variants were identical, and an opioid antagonist was able to enhance the maturation of both variants. We conclude that, instead of causing loss of function, Phe27Cys polymorphism of the hδOR causes a gain‐of‐function phenotype, which may have implications for the regulation of receptor expression at the cell surface and possibly also for the susceptibility to pathophysiological states.
NOSTRINβ– A Shortened NOSTRIN Variant with A Role in Transcriptional Regulation
Authors: Wiesenthal Anja , Hoffmeister Meike , Siddique Masood , Kovacevic Igor , Oess Stefanie , Müller‐Esterl Werner , Siehoff‐Icking Ann
Published: January 2009

We recently observed that a novel, shortened variant of eNOS trafficking inducer (NOSTRIN) is expressed in cirrhotic liver. This shortened variant (NOSTRINβ) lacks the first 78 amino acids of full‐length NOSTRIN (NOSTRINα) and thus a substantial part of its F‐BAR domain. In contrast to NOSTRINα, NOSTRINβ mainly localizes to the cell nucleus. In this study, we show that nuclear import of NOSTRINβ depends on two nuclear localization signals (aa 32–36: KKRK and aa 57–61: KAKKK). Each of the sequences is independently functional, but both are required to sustain nuclear localization of NOSTRINβ. Export of NOSTRINβ from the nucleus is facilitated by a CRM1‐dependent mechanism relying on the nuclear export sequence LELEKERIQL (aa 135–145). Unlike NOSTRINβ, the full‐length variant NOSTRINα was conspicuously absent from the nucleus. This is most likely because of the fact that its N‐terminal F‐BAR domain, which is truncated in NOSTRINβ, facilitates association with cellular membranes. NOSTRINβ directly binds to the 5′‐regulatory region of the NOSTRIN gene (bp −200 to −1), and overexpression of NOSTRINβ strongly decreases transcription of a reporter gene under control of this DNA region. Taken together, our results suggest that nuclear NOSTRINβ may negatively regulate transcription of the NOSTRIN gene.
Reconceptualizing the core of nurse practitioner education and practice
Authors: Burman Mary E. , Hart Ann Marie , Conley Virginia , Brown Julie , Sherard Pat , Clarke Pamela N
Published: January 2009

Purpose: The movement to the doctor of nursing practice (DNP) is progressing rapidly with new programs emerging and curricular documents being developed. We argue that the implementation of the DNP is a good move for nursing, provided that we use the opportunity to reconceptualize the core of advanced practice nursing, especially nurse practitioner (NP) practice.

Data sources: Theory and research articles from nursing focused on advanced practice nursing, NPs, and doctoral education.

Conclusions: The foundation of NP education is currently based essentially on borrowed or shared content in assessment, pharmacology, and pathophysiology. We argue that the heart and soul of nursing is in health promotion, both in healthy persons and in those dealing with chronic illness. Current master’s programs do not prepare NPs to assume high‐level practice focused on health promotion and disease management using the latest theoretical developments in health behavior change, behavioral sciences, exercise physiology, nutrition, and medical anthropology. Although these are touched upon in most NP programs, they do not represent the core science of NP education and need to be a critical part of any DNP program.

Implications for practice: Ultimately, our vision is for NP care to be consistently “different,” yet just as essential as physician care, leading to positive outcomes in health promotion and disease management.
HBcAg‐pulsed dendritic cell vaccine induces Th1 polarization and production of hepatitis B virus‐specific cytotoxic T lymphocytes
Authors: Chen Weiwei , Shi Ming , Shi Feng , Mao Yuanli , Tang Zirong , Zhang Bin , Zhang Hui , Chen Liangen , Chen Liming , Xin Shaojie , Wang Fu‐sheng
Published: January 2009

Aim:  Dendritic cells (DCs) pulsed with HBsAg efficiently reverse the immune tolerance to hepatitis B virus (HBV) and induce HBV‐specific cytotoxic T lymphocyte (CTL) responses in transgenic mice and healthy volunteers. However, it is not clear whether HBV core antigen (HBcAg)‐pulsed DCs can effectively induce CD4+ helper T cells polarization into Th1, which contribute to the induction and maintenance of HBV‐specific CD8+ T cells in chronic hepatitis B (CHB) patients. To address this issue, we conducted this study and investigated whether HBcAg‐pulsed DCs could polarize Th1 cells and induce an HBcAg‐specific CTL response.

Methods:  HBcAg‐pulsed DCs were generated from 21 CHB patients. The capacity of the HBcAg‐pulsed DC vaccine to stimulate CD4+ and CD8+ T cells to produce IFN‐γ and IL‐4 was estimated by intercellular cytokine staining, and the HBcAg‐pulsed DCs derived from 10 humam leucocyte antigen (HLA)‐A2+ CHB patients were tested for the induction of HBV‐specific CTLs from autologous T cells by pentamer staining. The cytotoxicity of these CTLs was evaluated in vitro by flow cytometry.

Results:  The HBcAg‐pulsed DCs derived from CHB patients exhibited a stronger capacity to stimulate autologous CD4+ and CD8+ T cells to release IFN‐γ rather than IL‐4, which could induce HBV core 18‐27 specific CTLs, suggesting a specific cytotoxicity against T2 cells that had been loaded with the HBV core 18‐27 peptide in vitro.

Conclusion:  HBcAg‐pulsed DC vaccine derived from CHB patients efficiently induced autologous T cell polarization to Th1 and generation of HBV core 18‐27 specific CTLs.
Changes in B‐lymphocyte stimulator protein levels during treatment with albinterferon alfa‐2b in patients with chronic hepatitis C who have failed previous interferon therapy
Authors: Rustgi Vinod , Nelson David R. , Balan Vijayan , Abelson Robert D. , Fiscella Michele , Migone Thi‐Sau , Pulkstenis Erik , Subramanian G. Mani
Published: January 2009

Aim:  The pharmacodynamics of albinterferon alfa‐2b (alb‐IFN), a novel recombinant protein consisting of interferon‐α‐2b genetically fused to human albumin, was evaluated in patients with chronic hepatitis C with a previous non‐response to interferon‐α‐based therapy. B‐lymphocyte stimulator (BLyS) is an essential in vivo regulator of B‐lymphocyte homeostasis. This analysis examined the relationship between serum BLyS level and virologic response across a range of alb‐IFN doses.

Methods:  In all, 115 patients were randomized initially to three alb‐IFN treatment arms (900 and 1200 µg every two weeks [q2wk], and 1200 µg every four weeks) with weight‐based ribavirin, followed by sequential enrollment in two higher dose arms (1500 and 1800 µg q2wk). Serum BLyS level was assessed by enzyme‐linked immunosorbent assay.

Results:  Serum BLyS levels at baseline were lower in African‐Americans (P < 0.001). Significant BLyS inductions were observed at weeks 12 and 24 versus pretreatment; in general, serum BLyS levels returned to pretreatment levels following treatment completion. Induction of BLyS was greater in the highest dose group; a significant dose–response trend was observed at weeks 12 (P = 0.002) and 24 (P < 0.001), as well as a significant time trend, with further BLyS induction increases at week 24 versus 12 (P < 0.001). Week 24 BLyS level change correlated with hepatitis C virus RNA reduction (r = −0.28; P = 0.006), driven primarily by patients with BLyS increases > 400%, but did not correlate with sustained virologic response.

Conclusion:  Higher alb‐IFN doses demonstrated dose‐related BLyS increases, although the correlation with virologic response was modest.
Two Kinds of Self‐Knowledge
Authors: BOYLE MATTHEW
Published: January 2009

I argue that a variety of influential accounts of self‐knowledge are flawed by the assumption that all immediate, authoritative knowledge of our own present mental states is of one basic kind. I claim, on the contrary, that a satisfactory account of self‐knowledge must recognize at least two fundamentally different kinds of self‐knowledge: an active kind through which we know our own judgments, and a passive kind through which we know our sensations. I show that the former kind of self‐knowledge is in an important sense fundamental, since it is intimately connected with the very capacity for rational reflection, and since it must be present in any creature that understands the first‐person pronoun. Moreover, I suggest that these thoughts about self‐knowledge have a Kantian provenance.
Use of destained cytology slides for the application of routine special stains
Authors: Marcos R. , Santos M. , Santos N. , Malhão F. , Ferreira F. , Monteiro R.A.F. , Rocha E.
Published: January 2009

Background: Special stains to demonstrate microorganisms or intra‐ and extracellular substances have not been evaluated in detail regarding their applicability and usefulness in destained cytologic specimens.

Objectives: The aim of this study is to compare the results of routine special stains on destained slides previously stained with Hemacolor and on fresh (unstained) specimens.

Methods: Archival Hemacolor‐stained fine needle aspirate specimens of inflammation with infectious agents (bacterial, mycobacterial, and fungal infections), neoplasia (melanoma, myxosarcoma, and mammary adenocarcinoma), and hemorrhage (pericardial effusion) from 14 dogs and 7 cats were selected. Cells in a minimum of 4 fields were photographed and 5 slides from each case were then destained by different methods (alcohol acid or microwave). Seven special stains were applied selectively to the destained slides, depending on the cytologic findings: periodic acid Schiff, Grocott–Gomori methenamine silver, Gram's, Ziehl–Neelsen, Alcian blue, Fontana–Masson, and Prussian blue. The same fields were rephotographed and 2 observers evaluated the slides qualitatively, with comparison to fresh cytologic specimens from similar lesions.

Results: Special stains applied to destained slides demonstrated the expected cellular and extracellular material or organisms independent of the destaining method. Staining intensity, nonspecific staining (background), cell morphology, and nuclear counterstaining results were similar to those of special stains applied to fresh unstained slides.

Conclusions: Destaining does not appear to affect the results of routine special staining for cytologic specimens. Destaining before special stains may be a valuable diagnostic strategy when few slides are present or only stained slides are available.
B‐cell lymphoma with Mott cell differentiation in two young adult dogs
Authors: Stacy Nicole I. , Nabity Mary B. , Hackendahl Nicole , Buote Melanie , Ward Jennifer , Ginn Pamela E. , Vernau William , Clapp William L. , Harvey John W.
Published: January 2009

Abstract: Two young adult dogs with gastrointestinal signs were each found to have an intra‐abdominal mass based on physical examination and diagnostic imaging. On exploratory laparotomy, small intestinal masses and mesenteric lymphadenopathy were found in both dogs; a liver mass was also found in dog 1. Cytologic and histologic examination of intestinal and liver masses and mesenteric lymph nodes revealed 2 distinct lymphoid cell populations: lymphoblasts and atypical Mott cells. With Romanowsky stains, the atypical Mott cells contained many discrete, clear to pale blue cytoplasmic inclusions consistent with Russell bodies that were positive by immunohistochemistry for IgM and CD79a in both dogs and for IgG in dog 2. The Mott cells and occasional lymphoblasts stained strongly positive with periodic acid‐Schiff. Using flow cytometric immunophenotyping in dog 1, 60% of peripheral blood mononuclear cells and 85% of cells in an affected lymph node were positive for CD21, CD79a, IgM, and MCH II, indicative of B‐cells. With electron microscopy, disorganized and dilated endoplasmic reticulum was seen in Mott cells in tumors from both dogs. Antigen receptor gene rearrangement analysis of lymph node and intestinal masses indicated a clonal B‐cell population. Based on cell morphology, tissue involvement, and evidence for clonal B‐cell proliferation, we diagnosed neoplasms involving Mott cells. To the authors' knowledge, this is the second report of Mott cell tumors or, more appropriately, B‐cell lymphoma with Mott cell differentiation, in dogs. More complete characterization of this neoplasm requires further investigation of additional cases. This lymphoproliferative disease should be considered as a differential diagnosis for canine gastrointestinal tumors.
What is your diagnosis? Rectal scraping from a dog with diarrhea
Authors: Chapman Seth , Thompson Craig , Wilcox Angela , Russell Karen
Published: January 2009

Abstract: A 3‐year‐old, spayed female, mixed‐breed dog was evaluated for chronic diarrhea, vomiting, and weight loss. A marked inflammatory leukogram, mild regenerative anemia, and marked hypoalbuminemia were noted. Cytologic evaluation of a rectal scraping revealed numerous round to ovoid protozoal cysts, 5–25 μm in diameter, with small to moderate amounts of pale blue cytoplasm and round eosinophilic nuclei. A distinct, variably sized, round to oval vacuole was often seen within the cytoplasm and frequently displaced the nucleus. The cysts were morphologically similar to Blastocystis sp., an amoeba‐like protozoal parasite found in both diseased and asymptomatic humans and animals. Histologic findings in endoscopic biopsies from the stomach, duodenum, ileum, and colon were unremarkable and protozoal organisms were not observed. The dog was diagnosed with exocrine pancreatic insufficiency based on markedly decreased serum levels of trypsin‐like immunoreactivity. Alteration of gastrointestinal flora secondary to the underlying pancreatic disease likely allowed overgrowth of the protozoa, which were considered an incidental finding. Their identification was important in avoiding an incorrect diagnosis and unwarranted treatment.
Disseminated histiocytic sarcoma with peripheral blood involvement in a Bernese Mountain dog
Authors: Rossi Silvia , Gelain Maria Elena , Comazzi Stefano
Published: January 2009

Abstract: A 6‐year‐old Bernese Mountain dog was presented with a history of lethargy and weight loss of 2 weeks duration. On physical examination the dog had pale mucous membranes and tachypnea. Ultrasound examination revealed hepatomegaly, splenomegaly, and mesenteric lymphadenomegaly. Results of a CBC included marked normocytic normochromic nonregenerative anemia, marked thrombocytopenia, and moderate leukocytosis with mild neutrophilia and a large population of unclassified round cells (6.2 × 103/μL). The unclassified cells occasionally were bi‐ or multinucleated and had variably abundant pale basophilic cytoplasm that contained multiple irregular clear vacuoles and occasionally erythrocytes. Fine needle aspirate specimens of the mesenteric lymph nodes and spleen were composed of a population of round pleomorphic cells with the same features as the circulating cells. On flow cytometric analysis of peripheral blood, the unclassified cells expressed CD18, CD45, CD11c, CD1c, and CD14; immunocytochemical analysis of blood smears also indicated the cells were positive for CD1c, CD1a, and CD11c. The dog died a few hours after referral. The histologic interpretation of samples collected from spleen, liver, and lymph nodes was malignant neoplasia of histiocytic origin. Immunohistochemical staining yielded negative results for CD11d, a marker of red‐pulp macrophages, ruling out hemophagocytic histiocytic sarcoma. Based on clinical and pathologic findings, the final diagnosis was disseminated histiocytic sarcoma (DHS) with peripheral blood involvement. To our knowledge, DHS in a dog with evidence and immunophenotyping of neoplastic cells in peripheral blood has been reported only rarely.
Linguistics and the Language Teacher
Authors: Hanzeli Victor E.
Published: January 2009

ABSTRACT: In this paper, delivered at the 1967 Annual Meeting of ACTFL in Chicago, it is claimed that the relationship between linguists and language teachers has been tainted with excessive claims on the part of some linguists and with servile imitation or misunderstanding on the part of some teachers, that the school of linguistic thought that created applied linguistics is being seriously challenged on theoretical grounds, and that the relevance of the new generative transformational grammar for language teaching is not yet apparent. On the positive side, it is noted that recent studies in linguistic theory and psycholinguistics tend to broaden our understanding of language and language learning, and that teachers who are willing to study it may contribute to this understanding and develop with linguists a relationship based on mutual respect and collaboration, rather than ignorant hostility or slavish bandwagoneering.
A Survey of FLES Instruction in Cities Over 300,000
Authors: Gradisnik Anthony
Published: January 2009

ABSTRACT: Forty‐two out of forty‐nine cities completed the survey which revealed that thirty‐one cities had a FLES program. Most of the cities begin their FLES program in grade four or below, and twenty‐eight of the thirty‐one cities offer FLES as part of the regular school day. At least three or more sessions of foreign language instruction per week are provided by twenty‐five cities. Television, as a medium of initial instruction, is used by nineteen cities and eleven of these prepare their programs locally. A table, listing all of the cities, indicates the year FLES began, languages, number of days per week, grades included, and type of program.
The Graduate School Foreign Language Requirement: A Survey of Testing Practices and Related Topics
Authors: Clark John L. D.
Published: January 2009

ABSTRACT: A questionnaire on doctoral level language requirements and testing practices was sent to 2,691 U.S. graduate school department chairmen in the spring of 1967. The following topics are presented from 1,604 return results: languages required or accepted for the doctoral degree; ways to meet the language requirement other than taking specific tests; the extent to which local examinations and Graduate School Foreign Language Tests (GSFLT) are used; test construction and score evaluation responsibilt ities within the institution; reactions by departmen‐chairmen to a proposal for new forms of the GSFLT; opinions of department chairmen on the relative usefulness of various language learning goals for doctoral students. Results are shown for the entire group of questionnaire respondents and for respondents categorized into Natural Sciences, Social Sciences, and Humanities areas. (Eight tables are included.)
State Certification and Proficiency Tests: The Experience in Pennsylvania
Authors: Perkins Jean A.
Published: January 2009

ABSTRACT: This paper is based on a report delivered to the Massachusetts Foreign Language Association at its fall meeting, 4 November 1967. It tells what has happened in Pennsylvania since the adoption in February 1965 of the requirement that all candidates for certification in a foreign language pass the MLA Foreign Language Proficiency Tests. The consensus of opinion among foreign language department heads at both the school and college level is strongly in favor of this means of assuring fluency in all four language skills. However, certain problems have arisen, and these are outlined along with suggestions for solving them.
Multi‐Level Grouping of Students in the Modern Foreign Language Program
Authors: Hernick Michael , Kennedy Dora
Published: January 2009

ABSTRACT: The recognition of varying language abilities and objectives among students persists as the main problem in organizing foreign language programs. The principal thesis emphasizes that the foreign language sequence represents a progressive acquisition of skills, a continuum rather than a series of discrete steps. A pilot program in a senior high school shows that a modified multi‐level grouping with built‐in flexibility for inter‐group movement of students is more successful than the conventional lock‐step one‐level‐per‐year arrangement in motivating and retaining students. Forcing students to move too rapidly creates not only failure, but also negative attitudes toward other cultures. One of the major findings in this pilot study has been the fact that many students who operated in the sub‐level groups were ready for on‐level courses upon entering the third year. Further, from a 50 percent failure rate in the foreign language programs, this factor is now no greater than that of the English program. The positive results of this multi‐level program point up the need for a reassessment of organizational patterns in recognition of the fact that larger segments of our society will be studying foreign languages.