bluuebunny/crossref_metadata_2025 huggingface dataset:
Japan's First Robot‐assisted Totally Endoscopic Mitral Valve Repair With a Novel Atrial Retractor
Authors: Ishikawa Norihiko , Watanabe Go , Tomita Shigeyuki , Nagamine Hiroshi , Yamaguchi Shojiro
Published: October 2009

This case report presents the first robot‐assisted totally endoscopic mitral valve plasty in Japan. A 54‐year‐old woman was found by echocardiography to have grade III mitral valve regurgitation because of prolapse of the posterior leaflet. Surgical repair was performed using the da Vinci Surgical System. For the totally endoscopic mitral valve repair, a right‐sided approach was used through four ports. A transthoracic aortic cross‐clamp and novel flexible port access retractor were inserted through a 5‐mm skin incision. Quadrangular resection of the posterior leaflet was performed, and an annuloplasty band was placed into the atrium. Resection of the valve segment took 13 min, and band implementation, 45 min. The total pump time was 197 min and the aortic cross‐clamp time, 117 min. Postoperative echocardiography confirmed the absence of mitral insufficiency.
Extended-Release Formulations of Antiepileptic Drugs: Rationale and Comparative Value
Authors: Perucca Emilio
Published: October 2009

Extended-release products are designed to prolong the absorption of drugs with short half-lives, thereby allowing longer dosing intervals while minimizing fluctuations in serum drug levels. The relationship between serum drug concentration and clinical effects of antiepileptic drugs (AEDs) can be complex and reducing fluctuations in serum drug levels is not equally advantageous for all AEDs. Extended-release formulations have been shown to be particularly valuable for carbamazepine, whereas for other AEDs advantages, other than prolongation of the dosing interval, have not been clearly demonstrated. Differences in bioavailability may exist between extended-release and immediate-release formulations and among different brands of extended-release products. Therefore, when switching from one formulation to another, careful monitoring of clinical response and attention to the need for dose adjustment are warranted.
Epilepsy and the Plastic Mind
Authors: Naegele Janice
Published: October 2009

Seizures are linked to many neuroplastic changes within hippocampal circuits, including alterations in neurogenesis and dendritic growth in the dentate gyrus. How do brief seizures cause the long-term plastic changes in the hippocampus that are associated with recurrent epilepsy? Recent experiments by Ma and colleagues provide insights. They demonstrate an epigenetic mechanism for long-lasting neuroplastic changes that is both activity-dependent and brain region-specific. Focusing on Gadd45b, a DNA excision repair gene, they show it is up-regulated after electroconvulsive seizures or glutamate dependent activation of NMDA receptors. Gadd45b demethylates DNA regulatory elements in promoters of genes encoding fibroblast growth factor 1 and brain-derived neurotrophic factor, increasing the expression of these genes within granule neurons of the dentate gyrus. These changes in growth factor expression promote neurogenesis in the subgranular zone and dendritic growth in the granule cell layer of the dentate gyrus. Further regional and temporal differences in the proliferation of astrocytes and microglia after seizures were demonstrated by two additional studies. Together this work highlights how activity-dependent epigenetic modifications to DNA can alter gene expression with remarkable regional and cell type specificity.
Waiting for Gadd45b
Authors: Parent Jack M.
Published: October 2009

Neuronal Activity-Induced Gadd45b Promotes Epigenetic DNA Demethylation and Adult Neurogenesis. Ma DK, Jang MH, Guo JU, Kitabatake Y, Chang ML, Pow-Anpongkul N, Flavell RA, Lu B, Ming GL, Song H. Science 2009 Feb 20;323(5917):1074–1077. The mammalian brain exhibits diverse types of neural plasticity, including activity-dependent neurogenesis in the adult hippocampus. How transient activation of mature neurons leads to long-lasting modulation of adult neurogenesis is unknown. Here we identify Gadd45b as a neural activity-induced immediate early gene in mature hippocampal neurons. Mice with Gadd45b deletion exhibit specific deficits in neural activity-induced proliferation of neural progenitors and dendritic growth of newborn neurons in the adult hippocampus. Mechanistically, Gadd45b is required for activity-induced DNA demethylation of specific promoters and expression of corresponding genes critical for adult neurogenesis, including brain-derived neurotrophic factor and fibroblast growth factor. Thus, Gadd45b links neuronal circuit activity to epigenetic DNA modification and expression of secreted factors in mature neurons for extrinsic modulation of neurogenesis in the adult brain.
Postnatal Influences on Seizure Susceptibility: Does My Mother Really Matter?
Authors: Barnes Gregory N.
Published: October 2009

Postnatal Epigenetic Influences on Seizure Susceptibility in Seizure-Prone versus Seizure-Resistant Rat Strains. Gilby KL, Sydserff S, Patey AM, Thorne V, St-Onge V, Jans J, McIntyre DC. Behav Neurosci 2009;123(2):337–346. The creation of seizure-prone (Fast) and seizure-resistant (Slow) rat strains via selective breeding implies genetic control of relative seizure vulnerability, yet ample data also advocates an environmental contribution. To investigate potential environmental underpinnings to the differential seizure sensitivities in these strains, the authors compared amygdala kindling profiles in adult male Fast and Slow rats raised by 1) their own mother, 2) a foster mother from the same strain, or 3) a foster mother from the opposing strain. Ultimately, strain-specific kindling profiles were not normalized by cross-fostering. Instead, both strains became more seizure-prone regardless of maternal affiliation (i.e., cross-fostered groups from both strains kindled faster than uncrossed controls). Interhemispheric seizure spread was also facilitated in cross-fostered Slow rat groups and was associated with increased commissural cross-sectional areas, giving them a Fast-like profile. It is important to note, however, that all Fast groups remained significantly more seizure-prone than Slow groups, suggesting that although the postnatal environment strongly influenced seizure disposition in both strains, it did not wholly account for their relative dispositions. Investigation into mechanisms fundamental to cross-fostering-induced seizure facilitation should help prevent postnatal worsening of pathology in already seizure-prone individuals.
Immediate and Long‐Term Outcome of Redo Percutaneous Mitral Valvuloplasty: Comparison with Initial Procedure in Patients with Rheumatic Mitral Restenosis
Authors: RIFAIE OSAMA , ISMAIL MOHAMED , NAMMAS WAIL
Published: October 2009

Aims: We explored the immediate and long‐term outcome of redo percutaneous mitral valvuloplasty (PMV) in a series of patients with mitral restenosis in comparison with initial PMV in the same series.

Methods: We enrolled 40 consecutive patients presenting with mitral restenosis after successful initial PMV. Redo PMV was performed by the antegrade transseptal approach using either the Inoue technique or the multitrack technique. Reassessment by transthoracic echocardiography was repeated 48 hours later, and annually thereafter. Procedural success was defined as 50% or more increase of mitral valve area (MVA) with a final MVA ≥1.5 cm2, without major complications. Restenosis was defined as loss of >50% of the initial gain of MVA by the preceding PMV with a final MVA <1.5 cm2.

Results: Procedural success was achieved in 37 (92.5%) patients. Both the initial and redo procedures were similar concerning the final MVA and mean transmitral pressure gradient (P > 0.05 for all). The gain of MVA was higher in the initial as compared to the redo procedure (P < 0.001). The initial mitral valve score correlated negatively with the final MVA in both the initial and redo procedures, and was the only independent predictor of the time to redo procedure, by multivariate regression analysis. At long‐term follow‐up (61 ± 2.8 months), the mean MVA was 1.6 ± 0.3 cm2. Three patients—out of 12 available for follow‐up—developed restenosis.

Conclusion: Redo PMV for mitral restenosis is feasible, safe, and achieves immediate and long‐term outcome comparable to initial PMV. (J Interven Cardiol 2010;23:1–6)
Androgen receptor coactivator p44/Mep50 in breast cancer growth and invasion
Authors: Peng Yi , Li Yirong , Gellert Lan Lin , Zou Xuanyi , Wang Jun , Singh Baljit , Xu Ruliang , Chiriboga Luis , Daniels Garrett , Pan Ruimin , Zhang David Y , Garabedian Michael J. , Schneider Robert J. , Wang Zhengxin , Lee Peng
Published: October 2009

Hormones and their receptors play an important role in the development and progression of breast carcinoma. Although the primary focus has been on oestrogen and oestrogen receptor (ER), androgen, androgen receptor (AR) and its coactivator(s) have been implicated in tumorigenesis of breast carcinoma and warrant further investigation. AR coactivator p44/Mep50 is identified as a subunit of methylosome complex and lately characterized as an AR coactivator that enhances AR mediated transcription activity in a ligand dependent manner. In prostate cancer, p44 is expressed in the nucleus of benign epithelia and translocated into the cytoplasm in cancer cells. Furthermore, nuclear expression of p44 inhibits prostate cancer growth. In this report, we examined the expression and function of p44 in breast cancer. In addition to being an AR coactivator, p44 also functions as an ER coactivator. In contrast to findings in prostate cancer, the expression of p44 shows strong cytoplasmic expression in morphologically normal terminal ductal lobular units, while nuclear p44 is observed in both ductal carcinoma in situ and invasive carcinoma. Further, overexpression of nuclear‐localized p44 stimulates proliferation and invasion in MCF7 breast cancer cells in the presence of oestrogen and the process is ERα dependent. These findings strongly suggest that p44 plays a role in mediating the effects of hormones during tumorigenesis in breast.
Aldehyde dehydrogenase activity promotes survival of human muscle precursor cells
Authors: Jean Elise , Laoudj‐Chenivesse Dalila , Notarnicola Cécile , Rouger Karl , Serratrice Nicolas , Bonnieu Anne , Gay Stéphanie , Bacou Francis , Duret Cédric , Carnac Gilles
Published: October 2009

Aldehyde dehydrogenases (ALDH) are a family of enzymes that efficiently detoxify aldehydic products generated by reactive oxygen species and might therefore participate in cell survival. Because ALDH activity has been used to identify normal and malignant cells with stem cell properties, we asked whether human myogenic precursor cells (myoblasts) could be identified and isolated based on their levels of ALDH activity. Human muscle explant‐derived cells were incubated with ALDEFLUOR, a fluorescent substrate for ALDH, and we determined by flow cytometry the level of enzyme activity. We found that ALDH activity positively correlated with the myoblast‐CD56+ fraction in those cells, but, we also observed heterogeneity of ALDH activity levels within CD56‐purified myoblasts. Using lentiviral mediated expression of shRNA we demonstrated that ALDH activity was associated with expression of Aldh1a1 protein. Surprisingly, ALDH activity and Aldh1a1 expression levels were very low in mouse, rat, rabbit and non‐human primate myoblasts. Using different approaches, from pharmacological inhibition of ALDH activity by diethylaminobenzaldehyde, an inhibitor of class I ALDH, to cell fractionation by flow cytometry using the ALDEFLUOR assay, we characterized human myoblasts expressing low or high levels of ALDH. We correlated high ALDH activity ex vivo to resistance to hydrogen peroxide (H2O2)‐induced cytotoxic effect and in vivo to improved cell viability when human myoblasts were transplanted into host muscle of immune deficient scid mice. Therefore detection of ALDH activity, as a purification strategy, could allow non‐toxic and efficient isolation of a fraction of human myoblasts resistant to cytotoxic damage.
Telomere attrition and genomic instability in xeroderma pigmentosum type‐b deficient fibroblasts under oxidative stress
Authors: Ting Aloysius Poh Leong , Low Grace Kah Mun , Gopalakrishnan Kalpana , Hande M. Prakash
Published: October 2009

Xeroderma pigmentosum B (XPB/ERCC3/p89) is an ATP‐dependent 3′→5′ directed DNA helicase involved in basal RNA transcription and the nucleotide excision repair (NER) pathway. While the role of NER in alleviating oxidative DNA damage has been acknowledged it remains poorly understood. To study the involvement of XPB in repair of oxidative DNA damage, we utilized primary fibroblasts from a patient suffering from XP with Cockayne syndrome and hydrogen peroxide (H2O2) to induce oxidative stress. Mutant cells retained higher viability and cell cycle dysfunction after H2O2 exposure. Cytokinesis blocked micronucleus assay revealed increased genome instability induced by H2O2. Single cell gel electrophoresis (comet) assay showed that the missense mutation caused a reduced repair capacity for oxidative DNA damage. Mutant fibroblasts also displayed decreased population doubling rate, increased telomere attrition rate and early emergence of senescent characteristics under chronic low dose exposure to H2O2. Fibroblasts from a heterozygous individual displayed intermediate traits in some assays and normal traits in others, indicating possible copy number dependence. The results show that a deficiency in functional XPB paradoxically renders cells more sensitive to the genotoxic effects of oxidative stress while reducing the cytotoxic effects. These findings have implications in the mechanisms of DNA repair, mutagenesis and carcinogenesis and ageing in normal physiological systems.
Viral interleukin‐6 encoded by rhesus macaque rhadinovirus is associated with lymphoproliferative disorder (LPD)
Authors: Orzechowska B.U. , Manoharan M. , Sprague J. , Estep R.D. , Axthelm M.K. , Wong S.W.
Published: October 2009

Background  Rhesus macaques (RM) co‐infected with simian immunodeficiency virus (SIV) and rhesus macaque rhadinovirus (RRV) develop abnormal cellular proliferations characterized as extra‐nodal lymphoma and retroperitoneal fibromatosis (RF). RRV encodes a viral interleukin‐6 (vIL‐6), much like Kaposi’s sarcoma‐associated herpesvirus, and involvement of the viral cytokine was examined in proliferative lesions.

Methods  Formalin fixed tissue from RM co‐infected with SIV and RRV were analyzed for RRV genomes by in situ hybridization and RRV vIL‐6 expression by immunofluorescence analysis.

Results  In situ hybridization analysis indicated that RRV is present in both types of lesions. Immunofluorescence analysis of different lymphomas and RF revealed positive staining for vIL‐6. Similarly to KS, RF lesion is positive for vimentin, CD117 (c‐kit), and smooth muscle actin (SMA) and contains T cell, B cell and monocytes/macrophage infiltrates.

Conclusions  Our data support the idea that vIL‐6 may be critical to the development and progression of lymphoproliferative disorder in RRV/SIV‐infected RM.
Resources for genetic management and genomics research on non‐human primates at the National Primate Research Centers (NPRCs)
Authors: Kanthaswamy S. , Capitanio J.P. , Dubay C.J. , Ferguson B. , Folks T. , Ha J.C. , Hotchkiss C.E. , Johnson Z.P. , Katze M.G. , Kean L.S. , Michael Kubisch H. , Lank S. , Lyons L.A. , Miller G.M. , Nylander J. , O’Connor D.H. , Palermo R.E. , Smith D.G. , Vallender E.J. , Wiseman R.W. , Rogers J.
Published: October 2009

Abstract The National Primate Research Centers (NPRCs) established Working Groups (WGs) for developing resources and mechanisms to facilitate collaborations among non‐human primate (NHP) researchers. Here we report the progress of the Genome Banking and the Genetics and Genomics WGs in developing resources to advance the exchange, analysis and comparison of NHP genetic and genomic data across the NPRCs.

The Genome Banking WG has established a National NHP DNA bank comprising 1250 DNA samples from unrelated animals and family trios from the 10 NHP species housed within the NPRC system. The Genetics and Genomics WG is developing SNP arrays that will provide a uniform, highly informative, efficient and low‐cost method for rhesus and long‐tailed macaque genotyping across the eight NPRCs. This WG is also establishing a Biomedical Informatics Research Network‐based portal for shared bioinformatics resources including vital statistics, genotype and population data and information on the National NHP DNA bank.
Characterization of cerebrospinal fluid monoamine metabolites in peripubertal chimpanzees (Pan troglodytes)
Authors: Fontenot M.B. , Musso M.W. , Watson S.L. , Anderson G.M.
Published: October 2009

Background  Assessment of cerebrospinal (CSF) monoamine metabolites 5‐hydroxyindoeacetic acid (5‐HIAA) and homovanillic acid (HVA), and the serotonin precursor tryptophan (TRP), in chimpanzees may help in understanding the neurobiology underlying aggressive, impulsive behavior in humans and non‐human primates.

Methods  Two CSF samples were obtained from 11 peripubertal chimpanzees 8 months apart and were assayed for monoamine metabolite and TRP concentrations.

Results  Substantial inter‐individual stability was observed for 5‐HIAA (n = 11; r = 0.83, P < 0.001) and HVA (r = 0.91, P < 0.001). Females had significantly higher concentrations of 5‐HIAA compared to males (F1,8 = 7.31; P < 0.05). Levels of 5‐HIAA (r = −0.62, P < 0.05), HVA (r = −0.86, P < 0.001) and TRP levels (r = −0.67; P < 0.05) decreased with age.

Conclusion  Close parallels were observed between chimpanzees and humans with respect to absolute levels, sex effects, ontogeny, and 5‐HIAA‐HVA correlations, supporting the potential utility of the measures in understanding relationships between monoamine functioning and behavior in chimpanzees and humans.
Single muscle fiber properties in aging and disuse
Authors: Canepari M. , Pellegrino M. A. , D'Antona G. , Bottinelli R.
Published: October 2009

Since the middle of the 1980s, it was understood that myosin, the motor of contraction, can be expressed in several isoforms. The isoforms of the myosin heavy‐chain (MHC) portion of the molecule were found to be mostly responsible for the diversity in the contractile and energetic properties of muscle fibers. In humans, three MHC isoforms are expressed in limb muscles (MHC‐1, MHC‐2A and MHC‐2X) and they generate three pure fiber types (types 1, 2A and 2X) and two hybrid types (types 1‐2A and ‐2AX). Type 1, 2A and 2X fibers widely differ with respect to most of their contractile and energetic properties, and a change in their relative distribution within muscles is known to modulate their functional properties in vivo through a “qualitative” mechanism. On the basis of the MHC regulation of muscle fibers properties, it is expected that a given fiber type develops the same force and shortens at the same speed regardless of the physiologic and pathologic conditions under which the muscle works. Surprisingly, several evidences have been accumulating to show that in aging and disuse, the properties of a muscle fiber type can change with no change in its myosin isoform content. This short review considers the latter phenomenon and the possible underlying mechanisms.
Maturational changes in the feeding behaviour of infants – a comparison between breast‐feeding and bottle‐feeding
Authors: Taki M , Mizuno K , Murase M , Nishida Y , Itabashi K , Mukai Y
Published: October 2009

Aim:  To obtain a better understanding of the changes in feeding behaviour from 1 to 6 months of age. By comparing breast‐ and bottle‐feeding, we intended to clarify the difference in longitudinal sucking performance.

Methods:  Sucking variables were consecutively measured for 16 breast‐fed and eight bottle‐fed infants at 1, 3 and 6 months of age.

Results:  For breast‐feeding, number of sucks per burst (17.8 ± 8.8, 23.8 ± 8.3 and 32.4 ± 15.3 times), sucking burst duration (11.2 ± 6.1, 14.7 ± 8.0 and 17.9 ± 8.8 sec) and number of sucking bursts per feed (33.9 ± 13.9, 28.0 ± 18.2 and 18.6 ± 12.8 times) at 1, 3 and 6 months of age respectively showed significant differences between 1 and 6 months of age (p < 0.05). The sucking pressure and total number of sucks per feed did not differ among different ages. Bottle‐feeding resulted in longer sucking bursts and more sucks per burst compared with breast‐feeding in each month (p < 0.05).

Conclusion:  The increase in the amount of ingested milk with maturation resulted from an increase in bolus volume per minute as well as the higher number of sucks continuously for both breast‐ and bottle‐fed infants.
Meta‐analysis of blood pressure tracking from childhood to adulthood and implications for the design of intervention trials
Authors: Toschke AM , Kohl L , Mansmann U , Von Kries R
Published: October 2009

Aim:  Blood pressure (BP) is related with cardiovascular disease. BP tracking in childhood and its implication for intervention trials are unknown.

Methods:  A systematic review and meta‐analysis were conducted to estimate BP tracking.

Results:  In 29 independent studies on 27 820 subjects, follow‐up length and baseline age were associated with systolic BP tracking (both p < 0.05), while gender, BP measurement method and study place were not (p = 0.215, p = 0.185 and p = 0.391). The overall adjusted systolic BP correlation coefficient was 0.44 between 10 and 11 years and decreased to 0.37 between 10 and 20 years. Comparison of BP changes before and after intervention need a 26% increased sample size for a 10‐year follow‐up of 10 year olds, while trials comparing BP values at study end only require smaller sample sizes.

Conclusion:  Blood pressure tracking from childhood to adulthood affects trials assessing long‐term effects on BP and was low‐to‐moderate. Therefore, regular BP controls are also needed in children with normal BP measurements possibly identifying hypertensive children earlier. A slight short‐term intervention effect on BP may not have any long‐term effects because of low BP tracking and its decrease by age.
The occurrence and significance of fibronectin in livers from chronic alcoholics
Authors: JUNGE JETTE , HORN THOMAS , CHRISTOFFERSEN PER
Published: October 2009

The occurrence and distribution of fibronectin (FN) was assessed by an immunoperoxidase technique in liver biopsies from alcoholics without and with acinar zone 3 fibrosis of varying degrees. Increased amounts of FN was found diffusely in zone 3 areas with a perisinusoidal and pericellular localization. FN was closely correlating to the pattern of fibrosis but increased amounts of FN could also be seen in biopsies without fibrosis as visualized in Picro‐Sirius stained sections. There was no topographical relationship to liver cells with fatty changes, Mallory bodies or to alcoholic hepatitis. It is made probable that FN is of significance in the development of early liver fibrosis in alcoholics and that FN may act as a chemotactic factor for collagen producing cells and as a skeleton for the new collagen formation.
Neisseria meningitidis: Occurrence in non‐pneumonic pulmonary infections
Authors: CHRISTENSEN J. J. , GADEBERG O. , BRUUN B.
Published: October 2009

A two‐year survey at our hospital revealed 19 patients suspected of pulmonary infection from whom Neisseria meningitidis was isolated from lower respiratory tract specimens, in 17 cases in pure culture. Of the isolates, 16, two and one belonged to serogroup B, C and 29E, respectively. All except three patients suffered from chronic pulmonary disease, notably chronic bronchitis. It was found likely or possible that N. meningitidis was the causative agent in 12 patients with symptoms of acute bronchitis. Results of tests for complement‐fixing antibodies against N. meningitidis (MAT) were generally not found to be useful when assessing the possible causative role of N. meningitidis in non‐pneumonic pulmonary infections.
Comparison of tests for heterophile antibodies with a test for specific IgM‐antibodies to Epstein‐Barr virus
Authors: MYRMEL HELGE
Published: October 2009

Seventy serum samples from 54 patients with clinically suspected infectious mononucleosis were examined, using the Paul‐Bunnell‐Davidsohn test, a rapid slide test and an ELISA for the detection of IgM antibodies against the viral capsid antigen (VCA) of Epstein‐Barr virus. The ELISA technique was the most sensitive, detecting IgM in 29 sera, whereas only 19 sera were positive in the Paul‐Bunnell‐Davidsohn test (titre ≥ 64). However, using a titre of ≥ 32 as a diagnostic level, the number of positive sera was 23, the same as for the rapid slide test. There was a high agreement (91%) between the heterophile antibodies tests and the VCA‐IgM ELISA. The Paul‐Bunnell‐Davidsohn test still holds a place in the serologic diagnosis of infectious mononucleosis, but sera should always be tested for VCA‐IgM in cases of heterophile antibodies negative mononucleosis.
Crossed immuno‐electrophoretic analysis of Yersinia enterocolitica serotype 0:3 antigens
Authors: PÆRREGAARD ANDERS , ESPERSEN FRANK , BÆK LEIF , HØIBY NIELS
Published: October 2009

By means of quantitative immuno‐electrophoretic methods, 81 different antigens were demonstrated in sonicated preparations of Yersinia enterocolitica, serogroup 0:3, using corresponding rabbit antiserum. Only chromosomally‐encoded antigens were demonstrated in this system. Thirteen antigens were located on the bacterial surface, as demonstrated after absorption of rabbit antiserum with whole, killed bacteria. Five antigens resisted boiling. Antigen No. 71 was identified as an important part of the lipopolysaccharide, and antigen No. 6 as the “common antigen” of Pseudomonas aeruginosa. Binding activities to concanavalin A (indicating the presence of carbohydrates), to Limulus amoebocyte lysate and to polymyxin B (indicating the presence of possible endotoxin activity) were demonstrated for five, nine, and seven antigens, respectively. These observations, together with the presence of corresponding antibodies in pre‐immune rabbit sera, as well as cross‐reactivity with other Gram‐negative bacteria, indicate the biological importance of several of these antigens.
In vitro cytotoxic effect of α‐hemolytic Escherichia coli on human blood granulocytes
Authors: GADEBERG OLE V. , LARSEN SEVERIN OLESEN
Published: October 2009

The correlation of the in vitro cytotoxic effect of 107 α‐hemolytic strains of Escherichia coli with various other bacterial characteristics was investigated. Damage to human bloodgranulocytes in the presence of fresh or heated autologous plasma was quantified by measuring the release of chromium‐5 1 from labelled cells. 95 strains had a cytotoxic effect which was equal in the presence of fresh or heated plasma, whereas 12 strains showed an effect which was reduced in fresh compared with heated plasma. The cytotoxic effect increased as the number of bacteria per granulocyte was increased. The average size of the α‐hemolysin production of the strains was 185 HU 50/ml ranging from 3–25 19 HU 50/ml. The cytotoxic effect of the strains was directly correlated with the size of the α‐hemolysin production. The cytotoxic effect was not correlated with the 0‐antigen serotype or the type of infection from which the strains were derived. These results indicate that the ability to produce α‐hemolysin is the bacterial characteristic which is of decisive importance for the cytotoxicity of α‐hemolytic E. coli towards human blood granulocytes.
Large intramuscular spindle‐cell lipoma
Authors: SUND STÅLE , HORDVIK MARKUS , MÆHLE BJØRN , WALLØE ANDERS , MYKING ANDREAS
Published: October 2009

A case of a large spindle‐cell lipoma in an intramuscular (subfascial) localization is reported. The tumour occurred in a 58‐year‐old male patient and was localized subfascially in his left deltoid muscle. The tumour measured 20 × 8 × 8 cm; its weight was 780 grams. After initial biopsy, the tumour was extirpated. Microscopically, the tumour tissue consisted of mature fat cells and spindle‐cell areas in varying amounts, constituting a typical appearance of a spindle‐cell lipoma. There were no histological signs of malignancy. Especially, no areas of liposarcoma differentiation were detected. The patient is well, with no signs of recurrence, one and a half years after the operation. We have reviewed the literature on spindle‐cell lipoma, and we believe this is the first example of this neoplasm to be reported in an intramuscular (subfascial) localization.
Mucoepidermoid tumors of salivary glands
Authors: JENSEN OLE J. , POULSEN THOMAS , SCHIØDT TORBEN
Published: October 2009

Mucoepidermoid tumors of salivary glands are relative rare and it has often been difficult to correlate the patologic features and clinical aspects. The literature recommends long term follow‐up studies. The object of the present study was therefore to follow this recommendation. The clinico‐pathological features of 39 mucoepidermoid tumors are presented. The material was retrieved from the files of the pathological institute, Rigshospitalet, Copenhagen, during the period 1941–75. All patients, 24 males, 15 females, were followed for a minimum of 5 years. The lesions were classified into low grade (13 cases), intermediate grade (14 cases) and high grade (12 cases). The corresponding 5, 10 and 15 years cumulative survival rates were 92%, 92%, 92% for low grade, 47.4%, 47.4%, 35.5% for intermediate grade and 0%, 0%, 0% for high grade tumors. Thus we found a close correlation between pathology and clinical course. Furthermore, a 5 year observation period appeared an acceptable approach, because 17 of the 18 patients who succumbed of the disease, did so within 4 years following surgery. We consider all grades of mucoepidermoid tumors to be potential malignant. In our study one patient with a low grade tumor died of the disease.
Immuno‐histochemical and ultrastructural characteristics of a cyst‐forming sporozoon associated with encephalomyelitis and myositis in dogs
Authors: BJERKÅS INGE , PRESTHUS JOHN
Published: October 2009

Light‐microscopy, including immuno‐histochemical staining, and transmission and scanning electron microscopy were applied for the characterization of a Toxoplasma‐like parasite associated with encephalomyelitis and myositis in dogs of the boxer breed. Most parasites were tachyzoites, occurring in clusters, up to 60 μn in diameter, in parasitophorous vacuoles of host cells. Cyst stages with a definite cyst wall were few, but could be demonstrated in all cases. Immunostaining with antiserum against Toxoplasma gondii was negative, while both tachyzoites and bradyzoites were stained with serum from affected dogs. Ultrastructurally, the parasite was characterized by a great number of rhoptries, few amylopectin granules, lack of micropores in the tachyzoites, and the occurrence of numerous dense bodies in the bradyzoites. Numerous intravacuolar tubules were present in the space of the parasitophorous vacuole. The cyst wall resembled that of T. gondii. Until a definite host is found, the parasite may be regarded as an “orphan”, cyst‐forming sporozoon that is ultrastructurally different from other known protozoan parasites. It has a light‐microscopical similarity to T. gondii but is antigenically different.
The Peri‐Implantitis: Implant Surfaces, Microstructure, and Physicochemical Aspects
Authors: Mouhyi Jaafar , Dohan Ehrenfest David M. , Albrektsson Tomas
Published: October 2009

There are two ways of looking at secondary failures of osseointegration; one is to reflect on possible causes for the failure, the other focuses on the pathology per se. In the first case, background factors such as mechanical trauma (adverse loading) or inflammations/infections are being discussed as the cause of failure. Then peri‐implantitis is a term reserved for implant disturbance due to inflammation/infections only. However, irrespective of the original reason for the failure being adverse loading or inflammation/infection, the end result with bone resorption and inflammation may be very similar. Hence, in the present article, an alternative outlook has been chosen. Trigerring factors for peri‐implantitis are generally gathered under four categories: lesions of peri‐implant attachment, presence of aggressive bacteria, excessive mechanical stress, and corrosion. If only one of these factors would start a chain reaction leading to lesions, then the other factors may combine to worsen the condition. With other words, peri‐implantitis is a general term dependent on a synergy of several factors, irrespective of the precise reason for first triggering off symptoms.
Sleeping Implant in the Temporal Bone: Report of a Case with 20‐Year Follow‐Up
Authors: Granström Gösta , Gröndahl Hans‐Göran , Tjellström Anders
Published: October 2009

Background: There is limited knowledge of the long‐term fate of “sleeping” or nonloaded implants in the temporal bone.

Purpose: This article describes the fate of a fixture installed in the temporal bone that remained unloaded for 20 years.

Patient and Methods: A 25‐year‐old male with hemifacial microsomia had three osseointegrated implants installed for an auricular episthesis and bone‐anchored hearing aid (BAHA) in the left temporal bone in 1988. Two of the implants for the ear episthesis were activated the same year, but the fixture for the hearing aid was not uncovered until 2008. When the patient experienced hearing problems at his office, he wanted to reactivate the sleeping implant. An audiogram showed a maximum conductive hearing loss with good preserved cochlear function. Before reactivation, an Accuitomo three‐dimensional, cone beam computed tomography was performed. Resonance frequency analysis (RFA) using the Ostell technique was done when the implant was uncovered.

Results: Preoperative x‐ray investigation showed the sleeping implant to be well integrated in the temporal bone, covered with 1 mm bone, and with no signs of resorption. Geometric measurements correlating to the two loaded implants showed the sleeping implant to be positioned too close to these to be able to anchor a BAHA without interference with the episthesis. Surgical exploration was done to analyze the implant. The clinical status correlated well to that diagnosed from the x‐ray investigation. RFA revealed the implant to be well integrated. A new fixture and abutment for BAHA was installed in the temporal line and activated 2 months after surgery. The patient is today supplied with a BAHA.

Conclusion: It seems possible to use sleeping implants in the temporal bone even 20 years after installation.
Radiographic Features of Mandibular Trabecular Bone Structure in Hypodontia
Authors: Créton Marijn , Geraets Wil , Verhoeven Jan Willem , van der Stelt Paul F. , Verhey Hans , Cune Marco
Published: October 2009

Purpose: Radiographic parameters of mandibular trabecular bone structure between 67 subjects having hypodontia and those without were studied on digital panoramic radiographs.

Materials and Methods: Three regions of interest (ROI) were defined: the ascending ramus, apical of the mandibular molar and mesial of the first mandibular molar. The effects of the presence of hypodontia and the ROI on the mandibular trabecular bone structure were tested for statistical significance by means of multivariate analysis.

Results: Radiographic parameters of trabecular bone architecture were found to differ between various regions of the mandible (p = 0.000), but not between the group of hypodontia subjects and their controls (p = 0.23). There was no interaction effect between the ROIs and the two groups (p = 0.79). For people having hypodontia, some directional parameters of trabecular bone have a reverse correlation with the number of missing teeth. The fractal dimension and the number and perimeter of white segments in the binarized image correlate positively with the number of congenitally missing teeth.

Conclusions: A limited number of parameters of radiographic mandibular trabecular bone structure correlate with the number of missing teeth. However, a markable difference in radiographic parameters of mandibular trabecular bone structure between hypodontia and non‐hypodontia subjects could not be demonstrated.
Minimally Invasive Treatment for Papillae Deficiencies in the Esthetic Zone: A Pilot Study
Authors: Becker William , Gabitov Ildor , Stepanov Misha , Kois John , Smidt Ami , Becker Burton E.
Published: October 2009

Background: The presence of papillary deficiencies adjacent to dental implants or teeth presents an esthetic concern for the dental team and patients.

Purpose: The aim of this pilot project is to evaluate a new method for reducing or eliminating small papillary deficiencies. The use of a commercially available gel was evaluated as a possible method for enhancing deficient papillae.

Materials and Methods: Eleven patients, seven females and four males, with an average age of 55.8 years (ranging from 25 to 75 years) with 14 treated sites are included in this pilot study. Patients had a minimum of one papillary deficiency in the esthetic zone. Prior to treatment photographs were either taken at a 1:1 ratio or converted to a 1:1 ratio using a commercially available program. A standardization photographic device was not used. After administration of a local anesthetic, a 23‐gauge needle was used to inject less than 0.2 mL of a commercially available and Food and Drug Administration‐approved gel of hyaluronic acid 2–3 mm apical to the coronal tip of the involved papillae. Patients were seen every three weeks and treatment was repeated up to three times. Patients were followed from 6 to 25 months after initial gel application. A computer program measured changes in pixels between initial and final treatments. A formula was derived to determine percentage change in the negative space between initial and final examinations.

Results: Each site was individually evaluated. Three implant sites and one site adjacent to a tooth had 100% improvement between treatment examinations. Seven sites improved from 94 to 97%, three sites improved from 76 to 88%, and one site adjacent to an implant had 57% improvement.

Conclusion: Results from this pilot study are encouraging and present evidence that small papillary deficiencies between implants and teeth can be enhanced by injection of a hyaluronic gel. Improvements were maintained for a range of 6 to 25 months.
Factors affecting methane production and mitigation in ruminants
Authors: SHIBATA Masaki , TERADA Fuminori
Published: October 2009

Methane (CH4) is the second most important greenhouse gas (GHG) and that emitted from enteric fermentation in livestock is the single largest source of emissions in Japan. Many factors influence ruminant CH4 production, including level of intake, type and quality of feeds and environmental temperature. The objectives of this review are to identify the factors affecting CH4 production in ruminants, to examine technologies for the mitigation of CH4 emissions from ruminants, and to identify areas requiring further research. The following equation for CH4 prediction was formulated using only dry matter intake (DMI) and has been adopted in Japan to estimate emissions from ruminant livestock for the National GHG Inventory Report: Y = −17.766 + 42.793X − 0.849X2, where Y is CH4 production (L/day) and X is DMI (kg/day). Technologies for the mitigation of CH4 emissions from ruminants include increasing productivity by improving nutritional management, the manipulation of ruminal fermentation by changing feed composition, the addition of CH4 inhibitors, and defaunation. Considering the importance of ruminant livestock, it is essential to establish economically feasible ways of reducing ruminant CH4 production while improving productivity; it is therefore critical to conduct a full system analysis to select the best combination of approaches or new technologies to be applied under long‐term field conditions.
Crystal structure of the shutoff and exonuclease protein from the oncogenic Kaposi’s sarcoma‐associated herpesvirus
Authors: Dahlroth Sue‐Li , Gurmu Daniel , Haas Juergen , Erlandsen Heidi , Nordlund Pär
Published: October 2009

The Kaposi’s sarcoma‐associated herpesvirus protein SOX (shut off and exonuclease) and its Epstein–Barr virus homolog, BGLF5, are active during the early lytic phase and belong to the alkaline nuclease family. Both proteins have been shown to be bifunctional, being responsible for DNA maturation as well as host shutoff at the mRNA level. We present the crystal structure of SOX determined at 1.85 Å resolution. By modeling DNA binding, we have identified catalytic residues that explain the preferred 5′‐exonuclease activity of the alkaline nucleases. The presence of a crevice suitable for binding duplex DNA supports a role for herpes alkaline nucleases in recombination events preceding packaging of viral DNA. Direct interaction with dsDNA is supported by oligonucleotide binding data. Mutations specifically affecting host shutoff map to a surface region of the N‐terminal domain, implying an essential role in protein–protein interactions, and link the RNase activity of the enzyme to mRNA degradation pathways.
The nucleosome‐binding protein HMGN2 modulates global genome repair
Authors: Subramanian Mangalam , Gonzalez Rhiannon W. , Patil Hemangi , Ueda Takahiro , Lim Jae‐Hwan , Kraemer Kenneth H. , Bustin Michael , Bergel Michael
Published: October 2009

The HMGN family comprises nuclear proteins that bind to nucleosomes and alter the structure of chromatin. Here, we report that DT40 chicken cells lacking either HMGN2 or HMGN1a, or lacking both HMGN1a and HMGN2, are hypersensitive to killing by UV irradiation. Loss of both HMGN1a and HMGN2 or only HMGN2 increases the extent of UV‐induced G2–M checkpoint arrest and the rate of apoptosis. HMGN null mutant cells showed slower removal of UV‐induced DNA lesions from native chromatin, but the nucleotide excision repair remained intact, as measured by host cell reactivation assays. These results identify HMGN2 as a component of the global genome repair subpathway of the nucleotide excision repair pathway, and may indicate that HMGN2 facilitates the ability of the DNA repair proteins to access and repair UV‐induced DNA lesions in chromatin. Our finding that HMGNs play a role in global DNA repair expands the role of these proteins in the maintenance of genome integrity.
Cholesterol oxidase: biochemistry and structural features
Authors: Vrielink Alice , Ghisla Sandro
Published: October 2009

Cholesterol oxidases are bifunctional flavoenzymes that catalyze the oxidation of steroid substrates which have a hydroxyl group at the 3β position of the steroid ring system. The enzyme is found, in a wide range of bacterial species, in two forms: one with the FAD cofactor bound noncovalently to the enzyme; and one with the cofactor linked covalently to the protein. Here we discuss, compare and contrast the salient biochemical properties of the two forms of the enzyme. Specifically, the structural features are discussed that affect the redox potentials of the flavin cofactor, the chemical mechanism of substrate dehydrogenation by active‐center amino acid residues, the kinetic parameters of both types of enzymes and the reactivity of reduced enzymes with molecular dioxygen. The presence of a molecular tunnel that is proposed to serve in the access of dioxygen to the active site and mechanisms of its control by a ‘gate’ formed by amino acid residues are highlighted.
Cholesterol oxidase: physiological functions
Authors: Kreit Joseph , Sampson Nicole S.
Published: October 2009

An important aspect of catalysis performed by cholesterol oxidase (3β‐hydroxysteroid oxidase) concerns the nature of its association with the lipid bilayer that contains the sterol substrate. Efficient catalytic turnover is affected by the association of the protein with the membrane as well as the solubility of the substrate in the lipid bilayer. In this review, the binding of cholesterol oxidase to the lipid bilayer, its turnover of substrates presented in different physical environments, and how these conditions affect substrate specificity, are discussed. The physiological functions of the enzyme in bacterial metabolism, pathogenesis and macrolide biosynthesis are reviewed in this context.
Polypyrimidine tract‐binding protein is essential for early mouse development and embryonic stem cell proliferation
Authors: Shibayama Masaki , Ohno Satona , Osaka Takashi , Sakamoto Reiko , Tokunaga Akinori , Nakatake Yuhki , Sato Mitsuharu , Yoshida Nobuaki
Published: October 2009

Polypyrimidine tract‐binding protein (PTB) is a widely expressed RNA‐binding protein with multiple roles in RNA processing, including the splicing of alternative exons, mRNA stability, mRNA localization, and internal ribosome entry site‐dependent translation. Although it has been reported that increased expression of PTB is correlated with cancer cell growth, the role of PTB in mammalian development is still unclear. Here, we report that a homozygous mutation in the mouse Ptb gene causes embryonic lethality shortly after implantation. We also established Ptb−/− embryonic stem (ES) cell lines and found that these mutant cells exhibited severe defects in cell proliferation without aberrant differentiation in vitro or in vivo. Furthermore, cell cycle analysis and a cell synchronization assay revealed that Ptb−/− ES cells have a prolonged G2/M phase. Thus, our data indicate that PTB is essential for early mouse development and ES cell proliferation.
MicroRNA‐143 reduces viability and increases sensitivity to 5‐fluorouracil in HCT116 human colorectal cancer cells
Authors: Borralho Pedro M. , Kren Betsy T. , Castro Rui E. , Moreira da Silva Isabel B. , Steer Clifford J. , Rodrigues Cecília M. P.
Published: October 2009

MicroRNAs are aberrantly expressed in cancer; microRNA‐143 (miR‐143) is down‐regulated in colon cancer. HCT116 human colorectal cancer cells were used to investigate the biological role of miR‐143. Transient miR‐143 overexpression resulted in an approximate 60% reduction in cell viability. In addition, stable miR‐143 overexpressing cells were selected with G418 and exposed to 5‐fluorouracil. Increased stable expression of miR‐143 was associated with decreased viability and increased cell death after exposure to 5‐fluorouracil. These changes were associated with increased nuclear fragmentation and caspase ‐3, ‐8 and ‐9 activities. In addition, extracellular‐regulated protein kinase 5, nuclear factor‐κB and Bcl‐2 protein expression was down‐regulated by miR‐143, and further reduced by exposure to 5‐fluorouracil. In conclusion, miR‐143 modulates the expression of key proteins involved in the regulation of cell proliferation, death and chemotherapy response. In addition, miR‐143 increases the sensitivity of colon cancer cells to 5‐fluorouracil, probably acting through extracellular‐regulated protein kinase 5/nuclear factor‐κB regulated pathways. Collectively, the data obtained in the present study suggest anti‐proliferative, chemosensitizer and putative pro‐apoptotic roles for miR‐143 in colon cancer.