bluuebunny/crossref_metadata_2025 huggingface dataset:
Crippling HIV one mutation at a time
Authors: Allen Todd M. , Altfeld Marcus
Published: May 2008

Accumulating data suggest that not all human immunodeficiency virus (HIV)-1–specific immune responses are equally effective at controlling HIV-1 replication. A new study now demonstrates that multiple immune-driven sequence polymorphisms in the highly conserved HIV-1 Gag region of transmitted viruses are associated with reduced viral replication in newly infected humans. These data suggest that targeting these and other conserved viral regions may be the key to developing an effective HIV-1 vaccine.
Histopathological Evaluation of a Novel Radiofrequency Surgical Ablation System
Authors: Saltman Adam E. , Raju Narayan R. , Block Jon E.
Published: May 2008

Purpose

Using a porcine model, this feasibility study was undertaken to evaluate the histopathological characteristics of lesions created in the proximity of the pulmonary veins after ablation with a new endoscopic-guided radiofrequency device.

Methods

Five adult female swine underwent endoscopic surgical ablation on the epicardial surface of the beating heart. Histologic sections taken from around the pulmonary vein pedicle, representing 10 separate anatomic sites, underwent independent qualitative histopathological evaluation as well as quantitative histomorphometric measurement of lesion depth and section thickness.

Results

Sections from all five animals had histologically identical lesions, with the majority of ablation foci having pronounced thermal injury characterized by deep and extensive zones of acute myocardial necrosis in the absence of tissue charring. Fifty-seven percent (13 of 23) of the lesions were completely transmural and 91% (21 of 23) of the sections demonstrated ≥70% transmurality. No collateral injuries were noted.

Conclusions

This irrigated, suction-stabilized unipolar radiofrequency device can produce histologically transmural lesions around the pulmonary veins and is amenable to endoscopic-guided application on the beating heart.
DNA-binding transcription factor NF-1A negatively regulates JC virus multiplication
Authors: Ravichandran Veerasamy , Major Eugene O.
Published: May 2008

JC virus (JCV) DNA replication occurs in the nuclei of infected cells. The level of JCV genome expression depends on nucleotide sequences in the viral regulatory region and their interaction with host-cell nuclear transcription factors. Our previous studies showed a higher level of NF-1X in JCV-permissive cells compared with the other members of the NF-1 family, NF-1A, B and C, which suggests that NF-1X plays a positive role in JCV multiplication. It remained unclear whether a reduction in the level of NF-1A, which is expressed abundantly in JCV-non-permissive cell types, leads to an increase in JCV multiplication. In this study, we show that downregulation of NF-1A expression in JCV-non-susceptible progenitor and HeLa cells results in a reversion to susceptibility for JCV multiplication. These data demonstrate that a higher level of NF-1A protein in JCV-non-permissive cell types, compared with the level of NF-1X, may be acting as a negative regulator at the JCV promoter to control JCV multiplication.
Analysis of tobamovirus multiplication in Arabidopsis thaliana mutants defective in TOM2A homologues
Authors: Fujisaki Koki , Kobayashi Soko , Tsujimoto Yayoi , Naito Satoshi , Ishikawa Masayuki
Published: May 2008

The TOM2A gene of Arabidopsis thaliana encodes a four-pass transmembrane protein that is required for efficient multiplication of a tobamovirus, TMV-Cg. In this study, the involvement of three TOM2A homologues in tobamovirus multiplication in A. thaliana was examined. T-DNA insertion mutations in the three homologues, separately or in combination, did not affect TMV-Cg multiplication, whereas, in the tom2a genetic background, some combinations reduced it. This result suggests that the TOM2A homologues are functional in enhancing TMV-Cg multiplication, but their contribution is much less than TOM2A. Interestingly, the multiplication of another tobamovirus, Tomato mosaic virus, was not drastically affected by any combinations of the mutations in TOM2A and its homologues as far as we examined.
Cholesterol transporter ATP-binding cassette A1 (ABCA1) is elevated in prion disease and affects PrPC and PrPSc concentrations in cultured cells
Authors: Kumar Rajeev , McClain Denise , Young Rebecca , Carlson George A.
Published: May 2008

Prion diseases are transmissible neurodegenerative disorders of prion protein (PrP) conformation. Prion replication by conversion of benign PrPCisoforms into disease-specific PrPScisoforms is intimately involved in prion disease pathogenesis and may be initiated in cholesterol-rich caveolae-like domains (CLD). Concentrations of the cholesterol transporter ATP-binding cassette A1 protein (ABCA1) are elevated in pre-clinical scrapie prion-infected mice and in prion-infected cellsin vitro. Elevation of ABCA1 in prion-infected brain is not a direct consequence of local PrPScaccumulation, indeed levels of ABCA1 are comparable in brain regions that differ dramatically in the amount of PrPSc. Similarly, ABCA1 concentrations are identical in normal mice, transgenic mice overexpressing PrP and PrP knockout mice. In contrast, PrPCand PrPSclevels, but notPrnpmRNA, were increased by overexpression of ABCA1 in N2a neuroblastoma cells and scrapie prion-infected N2a cells (ScN2a). Conversely, RNAi-mediated knock down ofAbca1expression decreased the concentrations of PrPCin N2a cells and of PrPScin ScN2a cells. These results suggest that ABCA1's effects on PrPClevels are post-translational and may reflect an increase in of PrPCstability, mediated either indirectly by increasing membrane cholesterol and CLD formation or by other functions of ABCA1. The increased supply of PrPCavailable for conversion would lead to increased PrPScformation.
Human papillomavirus (HPV) genotypes and HPV16 variants in human immunodeficiency virus-positive Italian women
Authors: Tornesello Maria Lina , Duraturo Maria Luisa , Giorgi-Rossi Paolo , Sansone Matilde , Piccoli Roberto , Buonaguro Luigi , Buonaguro Franco Maria
Published: May 2008

Human immunodeficiency virus (HIV)-positive women have high rates of cervical squamous intraepithelial lesions (SIL) and concurrent human papillomavirus (HPV) infections with a variety of genotypes whose oncogenic risk is poorly documented. The prevalence and persistence of HPV genotypes and HPV16 variants were analysed in 112 HIV-positive and 115 HIV-negative Italian women. HIV-positive women were more likely than HIV-negative women to be infected by HPV at the initial examination (39.3 vs 13.9 %, P<0.001) and to have a higher period prevalence of HPV infection over a 3-year follow-up (43.8 % vs 17.4 %, P<0.001), regardless of CD4+ cell counts and anti-retroviral therapy. ‘High-risk’ and ‘probable high-risk’ HPVs (types 16, 18, 31, 33, 35, 45, 52, 58 and 66), among the 20 different viral genotypes identified, were predominant in HIV-positive (33.9 %) compared with HIV-negative (13.9 %) women. Among HIV-infected women, with normal cytology as well as with SIL of any grade, the most common genotypes were HPV16 followed by HPV81, -58, -72, -33 and -62. HPV16 isolates from 18 HIV-positive and eight HIV-negative women were classified into variant lineages based on sequencing analysis of E6 and E7 genes and the long control region. Whilst the HPV16 G350 European variant was prevalent in both HIV-positive (10.7 %) and -negative women (3.5 %), HPV16 African 2 variant was only detected in HIV-positive women (3.6 %), suggesting different sexual mixing behaviours. The increased prevalence of uncommon viral genotypes and HPV16 variants in HIV-positive Italian women underscores the need to target a wide range of HPV types in cervical screening of high-risk women.
The flexible C terminus of the rotavirus non-structural protein NSP4 is an important determinant of its biological properties
Authors: Rajasekaran Deepa , Sastri Narayan P. , Marathahalli Jagannath R. , Indi Shanthinath S. , Pamidimukkala Kiranmayee , Suguna Kaza , Rao C. Durga
Published: May 2008

The rotavirus non-structural protein NSP4 functions as the viral enterotoxin and intracellular receptor for the double-layered particles (DLP). The full-length protein cannot be expressed and/or purified to homogeneity from bacterial or insect cells. However, a bacterially expressed and purified mutant lacking the N-terminal 72 aa (ΔN72) was recently obtained from strains Hg18 and SA11 exhibiting approximately 17–20-, 150–200- and 13166–15800-fold lower DD50 (50% diarrhoea-inducing dose) values in suckling mice compared with that reported for the partially pure, full-length protein, a C-terminal M175I mutant and a synthetic peptide comprising aa 114–135, respectively, suggesting the requirement for a unique conformation for optimal functions of the purified protein. The stretch of approximately 40 aa from the C terminus of the cytoplasmic tail of the endoplasmic reticulum-anchored NSP4 is highly flexible and exhibits high sequence variation compared with the other regions, the significance of which in diarrhoea induction remain unresolved. Here, it was shown that every amino acid substitution or deletion in the flexible C terminus resulted in altered conformation, multimerization, trypsin resistance and thioflavin T (ThT) binding, and affected DLP binding and the diarrhoea-inducing ability of the highly diarrhoeagenic SA11 and Hg18 ΔN72 in suckling mice. These studies further revealed that high ThT fluorescence correlated with efficient diarrhoea induction, suggesting the importance of an optimal ThT-recognizable conformation in diarrhoea induction by purified NSP4. These results based on biological properties provide a possible conformational basis for understanding the influence of primary sequence variations on diarrhoea induction in newborn mice by purified NSP4s that cannot be explained by extensive sequence analyses.
Effects of viral silencing suppressors on tobacco ringspot virus infection in two Nicotiana species
Authors: Siddiqui Shahid Aslam , Sarmiento Cecilia , Kiisma Mariliis , Koivumäki Satu , Lemmetty Anne , Truve Erkki , Lehto Kirsi
Published: May 2008

This study investigated the effects of silencing suppressors derived from six different viruses (P1, P19, P25, HcPro, AC2 and 2b), expressed in transgenic Nicotiana tabacum and Nicotiana benthamiana plants, on the infection pattern of tobacco ringspot virus (TRSV) potato calico strain. In N. benthamiana, this virus produced an initial infection with severe systemic symptoms, but the infection was strongly reduced within a few weeks as the plant recovered from the infection. P25 and HcPro silencing suppressors effectively prevented recovery in this host, allowing continuous accumulation of the viral RNA as well as of the virus-specific small interfering RNAs, in the systemically infected leaves. In the P1-, P19-, AC2- or 2b-expressing transgenic N. benthamiana, the recovery was not complete. Susceptibility of N. tabacum to this virus was temperature sensitive. At lower temperatures, up to 25 °C, the plants became systemically infected, but at higher temperatures, the infections were limited to the inoculated leaves. In these preventative conditions, all silencing suppressor transgenes (except P25, which was expressed at very low levels) allowed the establishment of systemic infections. Very strong and consistent systemic infections were observed in HcPro- and AC2-expressing plants.
Prion propagation in mice lacking central nervous system NF-κB signalling
Authors: Julius C. , Heikenwalder M. , Schwarz P. , Marcel A. , Karin M. , Prinz M. , Pasparakis M. , Aguzzi A.
Published: May 2008

Prions induce highly typical histopathological changes including cell death, spongiosis and activation of glia, yet the molecular pathways leading to neurodegeneration remain elusive. Following prion infection, enhanced nuclear factor-κB (NF-κB) activity in the brain parallels the first pathological changes. The NF-κB pathway is essential for proliferation, regulation of apoptosis and immune responses involving induction of inflammation. The IκB kinase (IKK) signalosome is crucial for NF-κB signalling, consisting of the catalytic IKKα/IKKβ subunits and the regulatory IKKγ subunit. This study investigated the impact of NF-κB signalling on prion disease in mouse models with a central nervous system (CNS)-restricted elimination of IKKβ or IKKγ in nearly all neuroectodermal cells, including neurons, astrocytes and oligodendrocytes, and in mice containing a non-phosphorylatable IKKα subunit (IKKα
AA/AA). In contrast to previously published data, the observed results showed no evidence supporting the hypothesis that impaired NF-κB signalling in the CNS impacts on prion pathogenesis.
Recombination increases human immunodeficiency virus fitness, but not necessarily diversity
Authors: Vijay N. N. V. , Vasantika  , Ajmani Rahul , Perelson Alan S. , Dixit Narendra M.
Published: May 2008

Recombination can facilitate the accumulation of mutations and accelerate the emergence of resistance to current antiretroviral therapies for human immunodeficiency virus (HIV) infection. Yet, since recombination can also dissociate favourable combinations of mutations, the benefit of recombination to HIV remains in question. The confounding effects of mutation, multiple infections of cells, random genetic drift and fitness selection that underlie HIV evolution render the influence of recombination difficult to unravel. We developed computer simulations that mimic the genomic diversification of HIV within an infected individual and elucidate the influence of recombination. We find, interestingly, that when the effective population size of HIV is small, recombination increases both the diversity and the mean fitness of the viral population. When the effective population size is large, recombination increases viral fitness but decreases diversity. In effect, recombination enhances (lowers) the likelihood of the existence of multi-drug resistant strains of HIV in infected individuals prior to the onset of therapy when the effective population size is small (large). Our simulations are consistent with several recent experimental observations, including the evolution of HIV diversity and divergencein vivo. The intriguing dependencies on the effective population size appear due to the subtle interplay of drift, selection and epistasis, which we discuss in the light of modern population genetics theories. Current estimates of the effective population size of HIV have large discrepancies. Our simulations present an avenue for accurate determination of the effective population size of HIVin vivoand facilitate establishment of the benefit of recombination to HIV.
The beaver as an ecosystem engineer facilitates teal breeding
Authors: Nummi Petri , Hahtola Anna
Published: May 2008

Positive interactions are important in influencing communities. Facilitation is one such influence in which a species makes the environment more suitable for others species. Ecological engineers are powerful facilitators as they physically modify habitats in a way that alters resource availability. We studied the effect of beaver flooding on breeding success of a dabbling duck, the teal. Our long‐term (1988‐2001) study was conducted in a boreal area where dabbling ducks face resource limitation. We focused on two aspects of facilitation: resource enhancement and habitat amelioration. We found that pond use by teal broods systematically increased upon beaver flooding. Beaver ponds harboured more resource, i.e. aquatic invertebrates than undisturbed waters, and invertebrate abundance was reflected as enhanced teal brood density. Beaver inundated shores were shallower than those of other waters, making their habitat structure more favourable to ducklings. Consequently, teal brood mortality was lower in beaver ponds than in waters unaffected by beaver. In boreal areas beaver facilitate teal breeding by enhancing both resource abundance and habitat structure.
Steep past and future population decline in an arctic wader: dynamics and viability of Baltic Temminck's stintsCalidris temminckii
Authors: Koivula Kari , Pakanen Veli‐Matti , Rönkä Antti , Belda Eduardo‐Jorge
Published: May 2008

Decline of migrant wader populations worldwide implies that their demography may be affected by phenomena occurring in a large geographical scale. Knowledge about vital rates affecting population growth and viability helps in finding the processes behind the declines. We estimated the rate of population growth (λ) of a dramatically declined population of Temminck's stintsCalidris temminckiiusing a ten year capture–recapture data. We assessed the viability of the population by projections based on λ and its variation. We also studied sensitivity of λ to changes in vital rates (breeding success, recruitment and adult survival). Both adult and juvenile survival and breeding success were lower than c. 30 years earlier. Adult survival seemed to have dropped during the study period. Population growth appeared strongly negative and viability analyses predicted an almost certain extinction within a few decades. Adult survival formed the main component of the growth rate suggesting that population crash is mainly caused by a drop in adult survival. Still, sensitivity analyses showed that a moderate rise in adult survival or any other single vital rate would not make the population viable. Most probably, survival has dropped due to factors operating along migration routes and wintering areas, at sites shared by birds from other parts of the breeding range. Therefore, the observed population crash and decline in adult survival may indicate parallel changes in poorly monitored arctic populations. Migration habits (continental wide flyways and scattered wintering areas) imply that factors responsible for the drop in survival have a wide geographical range.
Clinical analysis of multibacillary leprosy patients after 1‐year fixed World Health Organization recommended multidrug therapy at Yangon General Hospital, Myanmar
Authors: KYAW Kyaw , TSOH Tin Mg , SWE San Yi Yi , NAGAOKA Yuzuru , TAKEZAKI Shinichiro , SUZUKI Koichi , ISHII Norihisa
Published: May 2008

This study included 200 randomly selected multibacillary leprosy cases who had completed 1 year of fixed World Health Organization recommended multidrug therapy (WHO‐MDT) without prior dapsone (DDS) monotherapy. The time interval after release from treatment varied from a few months to 8 years. All cases were clinically reviewed in 2006 by comparison with their old clinical records. Reactions, particularly reversal reactions, occurred frequently among patients who had completed MDT within the last 3 years. It was difficult to distinguish relapse cases and late reversal reactions in skin smear‐negative multibacillary cases. Based on bacteriological and histological analyses, one patient was confirmed to have relapsed 1 year after release from treatment. The overall relapse rate was 0.5%. No drug resistance mutations were detected by polymerase chain reaction or dot blot hybridization. The present study indicates that it is important to follow up patients for several years after completion of MDT in order to detect possible lepra reactions and relapses.
New entity, definition and diagnostic criteria of cutaneous adult T‐cell leukemia/lymphoma: Human T‐lymphotropic virus type 1 proviral DNA load can distinguish between cutaneous and smoldering types
Authors: AMANO Masahiro , KUROKAWA Motoki , OGATA Katsumi , ITOH Hiroshi , KATAOKA Hiroaki , SETOYAMA Mitsuru
Published: May 2008

Adult T‐cell leukemia/lymphoma (ATLL) has been divided into four subtypes up to now: (i) acute; (ii) lymphoma; (iii) chronic; and (iv) smoldering. Skin lesion(s) may be present and the cases showing less than 5% abnormal T‐lymphocytes in peripheral blood without involvement of other organs, have been classified as smoldering ATLL. However, this type of ATLL with skin manifestations had a worse prognosis than that without skin lesions. This study aimed to define and distinguish cutaneous ATLL lacking nodal lymphoma and leukemic change from smoldering ATLL. We propose an entity of cutaneous ATLL, which has less than 5% abnormal T lymphocyte in peripheral blood, a normal lymphocyte count (i.e. <4 × 109/L), no hypercalcemia and lactate dehydrogenase values of up to 1.5 times the normal upper limit. At least one of the histologically proven skin lesions should be present accompanying monoclonal integration of human T‐cell lymphotropic virus type 1 (HTLV‐1) proviral DNA in the skin lesion. Blood samples were collected from 41 HTLV‐1‐infected patients, 21 asymptomatic carriers, 16 patients with cutaneous ATLL and four patients with smoldering ATLL. HTLV‐1 proviral loads, soluble interleukin‐2 receptors and other parameters were examined in each case. HTLV‐1 proviral DNA loads in smoldering ATLL group are significantly higher than those in asymptomatic carrier and cutaneous ATLL group. Cutaneous ATLL may be a distinct entity that should be separated from smoldering ATLL clinically and virologically.
Large cell transformation mimicking regional lymphomatoid papulosis in a patient with mycosis fungoides
Authors: NAKAHIGASHI Kyoko , ISHIDA Yuya , MATSUMURA Yumi , KORE‐EDA Satoshi , OHMORI Katsuyuki , FUJIMOTO Masakazu , YAMASHITA Kyoko , KOTANI Hirokazu , SAKURAI Takaaki , MIYACHI Yoshiki
Published: May 2008

A 57‐year‐old Japanese man with tumor‐stage mycosis fungoides suddenly presented multiple small papules on the right chest. Histopathology of a biopsy specimen from the papules revealed medium‐to‐large pleomorphic lymphoid cells throughout the entire dermis but not in the epidermis, and the large cells expressed CD30 antigen. These newly‐developed papules underwent spontaneous remission in the following 3 months. We reviewed the reported cases of mycosis fungoides, which showed CD30‐positive large cell transformation and those of CD30‐positive lymphoproliferative disorders associated with mycosis fungoides.
Telomere length shortening in Langerhans cell histiocytosis
Authors: Bechan Gitanjali I. , Meeker Alan K. , Marzo Angelo M. De , Racke Frederick , Jaffe Ronald , Sugar Elizabeth , Arceci Robert J.
Published: May 2008

Langerhans cell histiocytosis (LCH) is a clonal, proliferative disorder of phenotypically immature CD1a+ Langerhans cells (LC). The aetiology of LCH is unknown and data supporting an immune dysregulatory disorder as well as a clonal neoplasm have been reported. Telomere shortening has been associated with cancers and premalignant lesions as well as promoting chromosomal instability. To determine whether LCH LC have altered telomere lengths, we used dual detection of CD1a expression by immunofluorescence and telomere length by fluorescence in situ hybridization of LCH LC and lymphocytes in local, multisystem and systemic LCH and compared these with telomere lengths of LC and lymphocytes in reactive lymph nodes. LCH LC showed significantly shorter telomere lengths than LC from reactive lymph nodes or unaffected skin. Lymphocyte telomere lengths showed similar profiles among the different samples. These data show a significant telomere shortening in LCH LC in all stages of disease involvement compared with LC from reactive lymph nodes, suggesting that LCH may share mechanisms of telomere shortening and survival with clonal preneoplastic disorders and cancer, although an initiating infectious or immune event is still possible.
A phase II clinical trial of intensive chemotherapy followed by consolidative stem cell transplant: long‐term follow‐up in newly diagnosed mantle cell lymphoma
Authors: Evens Andrew M. , Winter Jane N. , Hou Nanjiang , Nelson Beverly P. , Rademaker Alfred , Patton David , Singhal Seema , Frankfurt Olga , Tallman Martin S. , Rosen Steven T. , Mehta Jayesh , Gordon Leo I.
Published: May 2008

Mantle cell lymphoma (MCL) is associated with high relapse rates and poor survival when treated with conventional chemotherapy, with or without rituximab. We report the long‐term follow‐up of a phase II clinical trial using a new intensive multiagent chemotherapeutic regimen [cyclophosphamide, teniposide, doxorubicin and prednisone (CTAP) alternating with vincristine and high‐dose methotrexate and cytarabine (VMAC)] in newly diagnosed MCL. Following 4–6 cycles of CTAP/VMAC induction, patients aged ≤65 years proceeded to consolidative autologous haematopoietic stem cell transplantation (auto‐HSCT), while patients ≤55 years who had a HLA‐identical sibling received allogeneic‐HSCT (busulfan/cyclophosphamide conditioning for both). Twenty‐five untreated MCL patients enrolled on the protocol between 1997 and 2002. Among evaluable patients, overall response rate (ORR) was 74% following induction chemotherapy. Seventeen patients received HSCT (autologous‐13/allogeneic‐4). On intent‐to‐treat analysis, ORR for patients who received consolidative HSCT was 100% (complete remission 76%). Therapy was well‐tolerated with 4% treatment‐related mortality (including HSCT). The 5‐year event‐free‐survival (EFS) and overall survival (OS) for all patients was 35% and 50% respectively. Furthermore, at 66‐months median follow‐up, the 5‐year EFS and OS for patients who received consolidative auto‐HSCT was 54% and 75% respectively. Patients who received auto‐HSCT had improved outcomes compared to no auto‐HSCT (EFSP = 0·001; OSP = 0·0002). CTAP/VMAC induction followed by consolidative auto‐HSCT for newly diagnosed MCL is associated with high ORR and durable survival.
Clinical significance of nuclear non‐phosphorylated beta‐catenin in acute myeloid leukaemia and myelodysplastic syndrome
Authors: Xu Jinglan , Suzuki Momoko , Niwa Yousuke , Hiraga Junji , Nagasaka Tetsuro , Ito Masafumi , Nakamura Shigeo , Tomita Akihiro , Abe Akihiro , Kiyoi Hitoshi , Kinoshita Tomohiro , Naoe Tomoki
Published: May 2008

Wnt signaling activates the canonical pathway and induces the accumulation of non‐phosphorylated beta‐catenin (NPBC) in the nucleus. Although this pathway plays an important role in the maintenance of haematopoietic stem cells as well as in oncogenesis, the significance of nuclear NPBC remains unclear in malignant haematopoiesis. This study examined the expression of nuclear NPBC in bone marrow specimens from 54 and 44 patients with de novo acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS), respectively. On immunohistochemistry with an anti‐NPBC antibody, the nuclei were positively stained in 22 and 18 of AML and MDS specimens, respectively. Staining of nuclear NPBC was associated with AML subtypes (M6 and M7), low complete remission (CR) rate, and poor prognosis. Nuclear NPBC was also associated with a high score when using the International Prognostic Scoring System (IPSS) for MDS and with −7/−7q and complex karyotypes. These findings suggest that in situ detection of nuclear NPBC by immunohistochemistry could provide new insights into the pathogenesis and prognosis of AML and MDS.
Tumour necrosis factor‐induced gene expression in human marrow stroma: clues to the pathophysiology of MDS?
Authors: Stirewalt Derek L. , Mhyre Andrew J. , Marcondes Mario , Pogosova‐Agadjanyan Era , Abbasi Nissa , Radich Jerald P. , Deeg H. Joachim
Published: May 2008

Aberrant regulation of the tumour necrosis factor alpha gene (TNF) and stroma‐derived signals are involved in the pathophysiology of myelodysplasia. Therefore, KG1a, a myeloid leukaemia cell line, was exposed to Tnf in the absence or presence of either HS‐5 or HS‐27a cells, two human stroma cell lines. While KG1a cells were resistant to Tnf‐induced apoptosis in the absence of stroma cells, Tnf‐promoted apoptosis of KG1a cells in co‐culture experiments with stroma cells. To investigate the Tnf‐induced signals from the stroma cells, we examined expression changes in HS‐5 and HS‐27a cells after Tnf exposure. DNA microarray studies found both discordant and concordant Tnf‐induced expression responses in the two stroma cell lines. Tnf promoted an increased mRNA expression of pro‐inflammatory cytokines [e.g. interleukin (IL)6, IL8 and IL32]. At the same time, Tnf decreased the mRNA expression of anti‐apoptotic genes (e.g. BCL2L1) and increased the mRNA expression of pro‐apoptotic genes (e.g. BID). Overall, the results suggested that Tnf induced a complex set of pro‐inflammatory and pro‐apoptotic signals in stroma cells that promote apoptosis in malignant myeloid clones. Additional studies will be required to determine which of these signals are critical for the induction of apoptosis in the malignant clones. Those insights, in turn, may point the way to novel therapeutic approaches.
Identification of a thrombin‐interactive site within the FVIII A2 domain that is responsible for the cleavage at Arg372
Authors: Nogami Keiji , Saenko Evgueni L. , Takeyama Masahiro , Giddings John C. , Yoshioka Akira , Shima Midori
Published: May 2008

FVIII is activated by cleavage at Arg372, Arg740, and Arg1689 by thrombin. This study showed that an anti‐A2 monoclonal antibody, with a specific epitope for residues 484–509, and anti‐FVIII inhibitor alloantibodies with similar A2 epitopes, inhibited thrombin‐catalyzed FVIII activation. Sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis showed that cleavage at Arg372 but not at Arg740 occurred at approximately fourfold decreased rate in the presence of anti‐A2 antibody. Peptide 484–509 also inhibited co‐factor activation, consistent with inhibition of cleavage at Arg372. Direct binding studies using active‐site modified thrombin showed that a 484–509 peptide as well as the anti‐A2 antibodies blocked the A2‐thrombin binding. Furthermore, covalent cross‐linking was observed between the 484–509 peptide and thrombin following reaction with 1‐ethyl‐3‐(3‐dimethylaminopropyl)‐carbodiimide. Mutant A2 molecules in which the clustered basic residues in this sequence were converted to alanine were used to assess the binding reactions in a surface plasmon resonance‐based assay. Mutants R484A, R489A, R490A, H497A and K499A possessed two to fivefold lower affinity than wild‐type A2. These findings demonstrate that clustered basic residues within the 484–509 region of the A2 domain play a part of key role in thrombin‐binding, which is responsible for thrombin‐catalyzed FVIII activation by cleavage at Arg372.
Nodular pulmonary lesions in children after autologous stem cell transplantation: a source of misinterpretation
Authors: Fazekas Tamas , Wiesbauer Peter , Kronberger Martina , Wank Hans , Gadner Helmut , Dworzak Michael
Published: May 2008

In children with malignant disorders, autologous haematopoietic stem cell transplantation (HSCT) represents a therapeutic option, but several possible complications, such as life‐threatening pulmonary disease, make appropriate diagnostic procedures essential. We describe two cases with bronchiolitis obliterans with organizing pneumonia after HSCT, with a brief review of important differential diagnoses.
Litter type and soil minerals control temperate forest soil carbon response to climate change
Authors: RASMUSSEN CRAIG , SOUTHARD RANDAL J. , HORWATH WILLIAM R.
Published: May 2008

Temperate forest soil organic carbon (C) represents a significant pool of terrestrial C that may be released to the atmosphere as CO2 with predicted changes in climate. To address potential feedbacks between climate change and terrestrial C turnover, we quantified forest soil C response to litter type and temperature change as a function of soil parent material. We collected soils from three conifer forests dominated by ponderosa pine (PP; Pinus ponderosa Laws.); white fir [WF; Abies concolor (Gord. and Glend.) Lindl.]; and red fir (RF; Abies magnifica A. Murr.) from each of three parent materials, granite (GR), basalt (BS), and andesite (AN) in the Sierra Nevada of California. Field soils were incubated at their mean annual soil temperature (MAST), with addition of native 13C‐labeled litter to characterize soil C mineralization under native climate conditions. Further, we incubated WF soils at PP MAST with 13C‐labeled PP litter, and RF soils at WF MAST with 13C‐labeled WF litter to simulate a migration of MAST and litter type, and associated change in litter quality, up‐elevation in response to predicted climate warming. Results indicated that total CO2 and percent of CO2 derived from soil C varied significantly by parent material, following the pattern of GR>BS>AN. Regression analyses indicated interactive control of C mineralization by litter type and soil minerals. Soils with high short‐range‐order (SRO) mineral content exhibited little response to varying litter type, whereas PP litter enriched in acid‐soluble components promoted a substantial increase of extant soil C mineralization in soils of low SRO mineral content. Climate change conditions increased soil C mineralization greater than 200% in WF forest soils. In contrast, little to no change in soil C mineralization was noted for the RF forest soils, suggesting an ecosystem‐specific climate change response. The climate change response varied by parent material, where AN soils exhibited minimal change and GR and BS soils mineralized substantially greater soil C. This study corroborates the varied response in soil C mineralization by parent material and highlights how the soil mineral assemblage and litter type may interact to control conifer forest soil C response to climate change.
Dens invaginatus and treatment options based on a classification system: report of a type II invagination
Authors: Kristoffersen Ø. , Nag O. H. , Fristad I.
Published: May 2008

Aim  To give an overview of treatment options for dens invaginatus based on a classification system.

Summary  Dens invaginatus is a dental malformation which may give endodontic complications. Treatment may vary in relation to anatomy, and a classification system for dens invaginatus forms the basis for discussion. A clinical case, classified as a type II invagination (Oehlers’ classification), is also presented. Clinical and radiographic examination revealed an invagination penetrating into the apical third of the root canal in tooth number 12. The tooth was immature with an open apex, apical pathosis and a labial fistula. To control the infection, ultrasonic removal of the invagination was necessary, as the invagination prevented complete cleaning and shaping of the root canal. After chemo‐mechanical preparation and dressing with calcium hydroxide, an apical plug of MTA was placed, followed by restoration of the tooth with resin‐bonded composite. Healing of the lesion with hard tissue formation was confirmed at follow‐up.

Key learning points • Knowledge about classification and anatomical variations of teeth with dens invaginatus is important in endodontic decision making.

• A classification system may be helpful when treatment options are considered.

• Classification of dens invaginatus requires a thorough preoperative radiographic examination.
Oxygen release of tetra acetyl ethylene diamine (TAED) and sodium perborate combination
Authors: Çelik E. U. , Türkün M. , Yapar A. G. D.
Published: May 2008

Aim  To evaluate the effect of tetra acetyl ethylene diamine (TAED) on oxygen release from sodium perborate and to compare it with sodium perborate–hydrogen peroxide (H2O2) and sodium perborate–distilled water mixtures.

Methodology  Six groups were evaluated: control groups (groups I–III), sodium perborate was mixed with distilled water or 3% or 30% H2O2; experimental groups (groups IV–VI), sodium perborate was mixed with TAED in different ratios and then distilled water was added to these mixtures. The amount of oxygen released from the samples was measured with a digital oxygen meter at room temperature (25 °C) and body temperature (37 °C) after 1 min, 1–6 h and 12 h and on each day up to 1 week. The results were statistically evaluated by one‐way analysis of variance and post hoc Tukey’s tests.

Results  The TAED groups demonstrated significantly higher amounts of released oxygen after 1 min and 1 h at 25 °C and 1 min at 37 °C (P < 0.05). At all other measurement times, the amount of TAED in each mixture did not alter the amount or speed of oxygen release (P > 0.05).

Conclusions  Tetra acetyl ethylene diamine groups achieved their maximum oxygen release 2 h earlier at 25 °C and 1 h earlier at 37 °C than the other groups. Thus, TAED accelerated oxygen release from sodium perborate–distilled water mixtures regardless of its proportions up to 24 h.
In vitrosusceptibility of theStreptococcus millerigroup to antimicrobial peptides
Authors: Bartie K. L. , Devine D. A. , Wilson M. J. , Lewis M. A. O.
Published: May 2008

Aim To determine the susceptibility of strains of theStreptococcus millerigroup (SMG) to commercially available antimicrobial peptides.

Methodology Thirty strains of SMG from a range of sources were assessed for their susceptibility to 10 antimicrobial peptides of either human, animal or insect origin, using a double layer diffusion assay.

Results The majority of the test strains were sensitive to the amidated peptides, mastoparan (100%;n = 30), magainin 2 amide (95%;n = 21) and indolicin (91%;n = 23). Some strains were susceptible to cecropin B (30%;n = 30) and histatin (10%;n = 30), whilst no activity was observed for the defensins HNP‐1 and HNP‐2, histatin 8, cecropin P1 and magainin 2.

Conclusions The majority of strains were resistant to the human derived peptides. The ability to resist such peptides may be a factor in the colonisation of the oral cavity and the survival and initiation of infection in the pulp and root canal environment. Interestingly, the present study indicated that amidated and alpha helical peptides exhibit antimicrobial activity against SMG. Structural modification of these peptides may allow a targeted approach for the development of these substances as preventative or therapeutic agents.
Periapical radiographs overestimate root canal wall thickness during post space preparation
Authors: Souza E. M. , Bretas R. T. , Cenci M. S. , Maia‐Filho E. M. , Bonetti‐Filho I.
Published: May 2008

Aim  To evaluate differences between anatomic and radiographic measurements of root canal wall thickness (RCWT) after each root canal preparation stage during post placement.

Methodology  Twenty mandibular premolars with a single canal were decoronated and the roots embedded in resin using a teflon muffle. Roots were sectioned horizontally at a pre‐established level and canals were prepared for post placement. Endodontic hand files were used for root canal preparation, followed by Gates Glidden drills and Peeso reamers. Standardized radiographs and photographs at pre‐established measurement levels were taken before preparation, after root canal instrumentation, after Gates Glidden preparation and after Peeso enlargement. All images were digitized and RCWT at the mesial and distal walls measured (imagetool 3.0). Differences between radiographic and anatomic measurements were analysed with paired t‐tests. anova was used to compare the percentages of radiographic distortions.

Results  Regardless of the time‐point evaluated, RCWT determined by radiographs were greater than the respective anatomic measurements (P < 0.05). The difference detected at each stage was similar and constant (P > 0.05).

Conclusions  Throughout preparation for post placement, radiographic images overestimated the RCWT by approximately 25%, regardless of the clinical stage evaluated.
Aflatoxin levels in dried figs, nuts and paprika for export from Turkey
Authors: Bircan Cavit , Barringer Sheryl A. , Ulken Ulku , Pehlivan Rahsan
Published: May 2008

Three hundred and thirteen of 2643 dried fig, two of eighty hazelnut, sixteen of twenty‐eight pistachio, five of ten peanut and nineteen of twenty‐three paprika samples for export from Turkey were contaminated with total aflatoxins in the range of 0.2–162.76, 5.46–6.55, 2.31–63.11, 0.75–26.36 and 1.79–6.55 μg kg−1, respectively. Samples were collected from January to August 2007 and tested for aflatoxins (B1, B2, G1 and G2) by immunoaffinity column extraction using RP‐HPLC. Fifty‐six of the 313 dried fig, all of the contaminated hazelnut and pistachio, two of the sixteen peanut and three of the nineteen paprika samples exceeded the regulatory limits of the European Union. The ratio of the different types of aflatoxin present in each sample exhibited great variability. For example, of 313 contaminated fig samples, 159 contained only aflatoxin B1, eighty‐five contained B1 (49.7%) + G1 (50.3%), twenty‐two contained only G1, twenty contained B1 (89.4%) + B2 (10.6%), thirteen contained B1 (73.7%) + B2 (10.8%) + G1 (15.5%) and fourteen contained all four types, B1 (26%) + B2 (2.5%) + G1 (66.5%) + G2 (5%).
A study to evaluate nurse‐led on‐treatment review for patients undergoing radiotherapy for head and neck cancer
Authors: Wells Mary , Donnan Peter T , Sharp Lena , Ackland Caroline , Fletcher Janice , Dewar John A
Published: May 2008

Aims and objectives.  To evaluate a nurse‐led clinic for patients undergoing radiotherapy to the head and neck.

Background.  The side effects of radiotherapy to the head and neck are superimposed on already significant physical and psychological morbidity. Medical review clinics tend to focus on treatment complications and there is evidence that specialist nurses can provide more holistic care for patients. However, doubts have been raised about the appropriateness of nurse‐led review in this highly symptomatic and complex group.

Design.  This evaluation compared medical on‐treatment review (Phase 1) with a nurse‐led clinic (Phase 2) for patients having radiotherapy to the head and neck, using an historical control group.

Methods.  Twenty patients were reviewed by their consultant and 23 by a nurse specialist, using a clinic protocol. A mixed‐method approach to data collection was taken. Patients completed weekly quality of life questionnaires and were asked about their experiences of support and care. General practitioners completed a questionnaire about the communication received from the clinic. Checklists assessed the content of clinic consultations.

Results.  Patients valued the relationship developed with the nurse specialist, had longer, more frequent consultations and were more often referred to the multidisciplinary team. The nurse specialist managed 83% of consultations without referral to the consultant. Few significant differences in quality of life were found between the groups. There were indications that oral and nutritional problems were managed more effectively in the nurse‐led clinic, although emotional functioning was higher in the medical group. GPs were positive about the timing and content of information received.

Conclusions.  On‐treatment review for patients with head and neck cancer can be effectively managed by a nurse specialist.

Relevance to Practice.  Radiotherapy nurse specialists make an important contribution to the supportive care of patients with head and neck cancer. More investment is required to maximize their contribution.
The tailored implementation of the nursing programme ‘Coping with itch’
Authors: Os‐Medendorp Harmieke van , Eland‐de Kok Petra , Linge Roland van , Bruijnzeel‐Koomen Carla , Grypdonck Mieke , Ros Wynand
Published: May 2008

Aim.  The aim of the study was to implement the nursing programme ‘Coping with itch’.

Background.  The nursing programme ‘Coping with itch’ is intended to reduce itch and to help patients to cope with itch. The programme is carried out at a nurse clinic at the dermatology outpatient department. Implementation of this programme was undertaken in five hospitals in the Netherlands using the tailored implementation approach based on the contingency model of van Linge.

Method.  The implementation procedure started with a diagnostic interview to gather data on the characteristics of the dermatology outpatient departments subsumed in four dimensions: structure, human resource practices, culture and politics. These characteristics were then compared with the demands of the programme. Discrepancies between the demands of the new programme and the characteristics of each organization guided the choice of the implementation strategies. Implementation strategies were mostly directed at the structure or human resource dimensions. Then, the results of the implementation were examined according to three criteria: professional adherence, continuation and barriers, using nurses’ self‐report forms on the consultations and the Barriers and Facilitators questionnaire.

Results.  Seventy‐seven self‐report forms were completed by the nurses for first consultations at the itch clinic and 81 for follow‐up consultations.

Results concerning professional adherence show that nurses are able to carry out the programme ‘Coping with itch’. All five hospitals continued the itch clinic after completion of the implementation study. Two barriers to the implementation were frequently mentioned by the nurses: the necessary time investment and the lack of extra financial compensation.

Conclusion.  The use of a tailored implementation approach has led to the reasonably successful implementation of the nursing programme ‘Coping with itch’.

Relevance to clinical practice.  The contingency model is a useful model for the tailored implementation of a nursing programme in daily practice.
No longer hungry in hospital: improving the hospital mealtime experience for older people through action research
Authors: Dickinson Angela , Welch Carol , Ager Laurie
Published: May 2008

Aims and objectives.  This study aimed to improve the mealtime experience of older people in a hospital setting through helping staff to make changes to their clinical practice and the ward environment.

Background.  Poor nutritional care has been a persistent and seemingly intractable problem for many years.

Methods.  We used an action research design for the study, drawing on techniques from practice development to support the action phase of the work, including action learning, role modelling good practice and reflection. The ward context was explored at the beginning and end of the study using focus groups, interviews, observation and benchmarking.

Results.  Ward staff made a number of changes to their nursing practice. The most significant was that all staff became engaged with, prioritized and were involved in the mealtime, ensuring that there was sufficient time and expertise available to assist patients with eating.

Conclusions.  This study demonstrates that it is possible to change nursing practice at mealtimes and that this change leads to improvements in patients’ experience through ensuring they receive the help they need.

Relevance to clinical practice.  Although hospital mealtimes are frequently viewed as problematic, we have shown that nurses can be enabled to make changes to their practice that have a positive impact on both the mealtime experience and wider patient care.