bluuebunny/crossref_metadata_2025 huggingface dataset:
Central Composite Design Optimization of Biological Dye Removal in the Presence of Macroalgae Chara sp.
Authors: Khataee Ali R. , Dehghan Gholamreza , Ebadi Elahe , Pourhassan Minoo
Published: September 2010

Response surface methodology (RSM) was employed to investigate the effects of different operational parameters on the biological decolorization of a dye solution containing malachite green (MG) in the presence of macroalgae Chara sp. The investigated variables were the initial pH, initial dye concentration, algae amount, and reaction time. Central composite design (CCD) was used for the optimization of biological decolorization process. Predicted values were found to be in good agreement with experimental values (R2 = 0.982 and Adj‐R2 = 0.966), which indicated suitability of the employed model and the success of RSM. The results of optimization predicted by the model showed that maximum decolorization efficiency was achieved at the optimum condition of the initial pH 6.8, initial dye concentration 9.7 mg/L, algae amount 3.9 g, and reaction time 75 min. UV–VIS spectra and FT‐IR analysis showed degradation of MG.
The utility of napsin‐A in the identification of primary and metastatic lung adenocarcinoma among cytologically poorly differentiated carcinomas
Authors: Stoll Lisa M. , Johnson Michael W. , Gabrielson Edward , Askin Fredrick , Clark Douglas P. , Li Qing Kay
Published: September 2010

BACKGROUND:

New developments in the treatment of lung cancer have necessitated the further histologic and cytologic subtyping of nonsmall cell lung carcinomas. Thyroid transcription factor‐1 (TTF‐1) long has served as the predominant marker for demonstrating lung origin. However, it is also expressed in a variety of other tumors, particularly neuroendocrine neoplasms and, to a much lesser degree, squamous cell carcinoma of the lung. Napsin‐A, which is expressed in lung tissue, is a relatively new marker for lung adenocarcinoma. In this study, the authors examined the utility of napsin‐A compared with TTF‐1 in cytologic specimens of primary and metastatic, poorly differentiated lung adenocarcinomas.

METHODS:

The archives of the Department of Pathology at The Johns Hopkins Hospital were searched for cytologic cases of poorly differentiated lung adenocarcinoma that were histologically confirmed. In total, 75 patients (cases) along with 95 controls were included, each of whom had adequate cell block material for TTF‐1 and napsin‐A staining. Tissue microarrays of lung adenocarcinoma also were examined.

RESULTS:

TTF‐1 and napsin‐A were detected in 61 of 75 cases (81.3%) and in 49 of 75 cases (65.3%), respectively. The sensitivity and specificity of TTF‐1 were 81% each; and napsin‐A had a greater specificity of 96%, and sensitivity of 65%. Napsin‐A was not detected in small cell carcinomas or in other carcinomas of nonlung origin except for renal cell carcinoma.

CONCLUSIONS:

Although TTF‐1 had a higher sensitivity, napsin‐A was useful as a surrogate marker when encountering a poorly differentiated lung adenocarcinoma or an unknown primary tumor, particularly in cytologic specimens and difficult cases. The current results indicate that the dual use of both markers may be necessary to improve diagnostic accuracy. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.
Quantum Chemical Study of the Reaction between Ni+ and H2S
Authors: Lakuntza Oier , Matxain Jon M. , Ugalde Jesus M.
Published: September 2010

The reaction between the Ni+ cation and H2S is studied by considering both the doublet ground state and the lowest‐lying quartet state. For the doublet state the reaction is endothermic, whereas it is exothermic for the quartet state. Both CCSD(T)//B3LYP and B3LYP levels of theory, combined with the triple‐zeta quality TZVP++G(3df,2p), predict that there are three spin crossings along the characterized reaction path. The first one is located after the first transition state, and the second and third ones before and after the second transition state. On the quartet potential energy surface, both transition states are close in energy to the reactants, while on the doublet surface both lie quite higher in energy. The doublet and quartet states of the HNiSH+ four‐membered intermediate lie very close in energy and their corresponding electronic configurations are connected by a single electron flip. This suggests that the ‐SH ligand would not prevent a facile intersystem crossing at this intermediate molecule, in contrast to the larger protection provided by the more electronegative OH ligand.
Thermodynamics and Kinetics of the Complexation Reaction of Lead by Calix‐DANS4
Authors: Wu Ting , Leray Isabelle , Génot Valérie , Lefèvre Jean Pierre , Korovitch Alexandre , Ha‐Duong Nguyêt‐Thanh , El Hage Chahine Jean‐Michel , Delaire Jacques Alexis
Published: September 2010

The thermodynamics and kinetics of the complexation reaction between lead ions and the fluorescent sensor Calix‐DANS4 are determined to optimize the geometry of the microreactor used for the flow‐injection analysis of lead and to tune the working conditions of this microdevice. Under our experimental conditions (pH 3.2, low concentration of Calix‐DANS4) the 1:1 Pb2+‐Calix‐DANS4 complex is predominantly formed with a high stability constant (log K1:1=6.82) and a slow second‐order rate constant (k=9.4×104 L mol−1 s−1). Due to this sluggish complexation reaction, the microchannel length must be longer than 130 mm and the flow rate lower than 0.25 mL h−1 to have an almost complete reaction at the output of the microchannel and a high sensitivity for the heavy metal detection. After determination of the values of the reaction times in our different microdevices, it is possible to simulate the calibration curves for the fluorimetric detection of lead under different conditions. An original method is also presented to determine mixing times in microreactors.
Homogeneous Oxidation Reactions of Propanediols at Low Temperatures
Authors: Díaz Eva , Sad María Eugenia , Iglesia Enrique
Published: September 2010

O2 reacts with propanediols via homogeneous pathways at 400–500 K. 1,2‐Propanediol forms CH3CHO, HCHO, and CO2 via oxidative CC cleavage and acetone via dehydration routes, while symmetrical 1,3‐propanediol undergoes dehydration and oxidative dehydrogenation to form, almost exclusively, acrolein (ca. 90 % selectivity). The products formed and their kinetic dependence on reactant concentrations are consistent with radical‐mediated pathways initiated by O2 insertion into CH bonds in a β position relative to oxygen atoms in diol reactants. Propagation involves β‐scission reactions that form hydroxyl and hydroxyalkyl radicals. Acrolein/O2/H2O mixtures from the homogeneous oxidation of 1,3‐propanediol form acrylic acid (with 90 % yield) in tandem reactors containing molybdenum‐vanadium oxide catalysts. These data reveal the unique reactivity of diols, compared with triols and alkanols, in homogeneous oxidations, while also providing useful insight into the molecular basis for reactivity in biomass‐derived oxygenates.
Different biology and clinical outcome according to the absolute numbers of clonal B‐cells in monoclonal B‐cell lymphocytosis (MBL)
Authors: Rawstron Andy C. , Shanafelt Tait , Lanasa Mark C. , Landgren Ola , Hanson Curtis , Orfao Alberto , Hillmen Peter , Ghia Paolo
Published: September 2010

The biological and clinical relationship between Chronic Lymphocytic Leukaemia (CLL) and Monoclonal B‐cell Lymphocytosis (MBL) has now been reported in some detail. This review investigates associations between biology and disease activity as they relate to the absolute numbers of abnormal cells. The clonal B‐cells in CLL‐type MBL are indistinguishable from CLL with respect to surface phenotype and the presence of chromosomal abnormalities. However, the majority of CLL‐type MBL cases in the general population have very low numbers of clonal B‐cells, typically in the range 0.1–10 per μL, and such cases use different IGHV genes than higher‐count CLL‐type MBL cases and often show intraclonal heterogeneity. Cases with higher counts are biologically similar to CLL although there is a relationship between the CLL cell count at presentation and the likelihood of further clonal expansion. Individuals presenting with CLL cell counts above 2,000 per μL are more likely to have gradually increasing B‐cell counts over time and although the risk of requiring treatment for progressive CLL remains low there may be impaired normal B‐cell activity. © 2010 International Clinical Cytometry Society
The New Zealand black mouse as a model for the development and progression of chronic lymphocytic leukemia
Authors: Salerno Erica , Yuan Yao , Scaglione Brian J. , Marti Gerald , Jankovic Alexander , Mazzella Fermina , Fernanda Laurindo Maria , Despres Daryl , Baskar Sivasubramanian , Rader Christoph , Raveche Elizabeth
Published: September 2010

Background:

Similar to a subset of human patients who progress from monoclonal B lymphocytosis (MBL) to chronic lymphocytic leukemia (CLL), New Zealand Black (NZB) mice have an age‐associated progression to CLL. The murine disease is linked to a genetic abnormality in microRNA mir‐15a/16‐1 locus, resulting in decreased mature miR‐15a/16.

Methods:

Spleens of aging NZB were analyzed for the presence of B‐1 cells via flow cytometry and for the presence of a side population (SP) via the ability of cells to exclude Hoechst 33342 dye. The SP was assayed for the presence of hyperdiploid B‐1 clones and for the ability to differentiate into B‐1 cells in vitro and transfer disease in vivo. In addition, enhanced apoptosis of chemoresistant NZB B‐1 cells was examined by restoring miR‐16 levels in nutlin‐treated cells.

Results:

Aging NZB mice develop a B‐1 expansion and clonal development that evolves from MBL into CLL. An expansion in SP is also seen. Although the SP did contain increased cells with stem cell markers, they lacked malignant B‐1 cells and did not transfer disease in vivo. Similar to B‐1 cells, splenic NZB SP also has decreased miR‐15a/16 when compared with C57Bl/6. Exogenous addition of miR‐15a/16 to NZB B‐1 cells resulted in increased sensitivity to nutlin.

Conclusion:

NZB serve as an excellent model for studying the development and progression of age‐associated CLL. NZB SP cells do not seem to contain cancer stem cells, but rather the B‐1 stem cell. NZB B‐1 chemoresistance may be related to reduced miR‐15a/16 expression. © 2010 International Clinical Cytometry Society
Human peripheral blood B‐cell compartments: A crossroad in B‐cell traffic
Authors: Perez‐Andres M. , Paiva B. , Nieto W. G. , Caraux A. , Schmitz A. , Almeida J. , Vogt R. F. , Marti G. E. , Rawstron A. C. , Van Zelm M. C. , Van Dongen J. J. M. , Johnsen H. E. , Klein B. , Orfao A. ,   and the Primary Health Care Group of Salamanca for the Study of MBL
Published: September 2010

A relatively high number of different subsets of B‐cells are generated through the differentiation of early B‐cell precursors into mature B‐lymphocytes in the bone marrow (BM) and antigen‐triggered maturation of germinal center B‐cells into memory B‐lymphocytes and plasmablasts in lymphoid tissues. These B‐cell subpopulations, which are produced in the BM and lymphoid tissues, recirculate through peripheral blood (PB), into different tissues including mucosa and the BM, where long‐living plasma cells produce antibodies. These circulating PB B‐cells can be classified according to their maturation stage into i) immature/transitional, ii) naïve, and iii) memory B‐lymphocytes, and iv) plasmablasts/plasma cells. Additionally, unique subsets of memory B‐lymphocytes and plasmablasts/plasma cells can be identified based on their differential expression of unique Ig‐heavy chain isotypes (e.g.: IgM, IgD, IgG, IgA). In the present paper, we review recent data reported in the literature about the distribution, immunophenotypic and functional characteristics of these cell subpopulations, as well as their distribution in PB according to age and seasonal changes. Additional information is also provided in this regard based on the study of a population‐based cohort of 600 healthy adults aged from 20 to 80 years, recruited in the Salamanca area in western Spain. Detailed knowledge of the distribution and traffic of B‐cell subsets through PB mirrors the immune status of an individual subject and it may also contribute to a better understanding of B‐cell disorders related to B‐cell biology and homeostasis, such as monoclonal B‐cell lymphocytosis (MBL). © 2010 International Clinical Cytometry Society
Prevalence, clinical aspects, and natural history of IgM MGUS
Authors: McMaster Mary L. , Landgren Ola
Published: September 2010

Background:

Waldenström macroglobulinemia (WM) and chronic lymphocytic leukemia (CLL) are related B‐cell cancers that share several clinical and biological features. Both WM and CLL have associated precursor conditions: monoclonal gammopathy of undetermined significance (MGUS) of immunoglobulin M (IgM) type and monoclonal B‐cell lymphocytosis (MBL), respectively. Recently, a case of MBL with an IgM MGUS was reported, suggesting a close biological relationship between these entities. While much is known about MGUS overall, investigations of IgM MGUS specifically have been fragmentary.

Methods:

In this article, we review data on the prevalence, clinical aspects and natural history of IgM MGUS, and focus on identifying gaps in our understanding of the complex relationships among B‐cell malignancies and their precursors.

Results:

There appears to be marked heterogeneity in the prevalence of IgM MGUS across populations. However, studies have varied in definition, design, laboratory methods, and endpoints. IgM MGUS differs from non‐IgM MGUS in certain respects, including prevalence across racial groups, rate of progression, and pattern of malignant outcomes. There are limited data regarding the coincident occurrence of IgM MGUS and MBL.

Conclusions:

Future studies incorporating both protein electrophoresis and flow cytometry are needed to define the underlying spectrum and causes of precursor development, risk factors for progression, and markers that distinguish low‐ and high‐risk precursor patients. Published 2010 Wiley‐Liss, Inc.
Elucidation of seventeen human peripheral blood B‐cell subsets and quantification of the tetanus response using a density‐based method for the automated identification of cell populations in multidimensional flow cytometry data
Authors: Qian Yu , Wei Chungwen , Eun‐Hyung Lee F. , Campbell John , Halliley Jessica , Lee Jamie A. , Cai Jennifer , Kong Y. Megan , Sadat Eva , Thomson Elizabeth , Dunn Patrick , Seegmiller Adam C. , Karandikar Nitin J. , Tipton Christopher M. , Mosmann Tim , Sanz Iñaki , Scheuermann Richard H.
Published: September 2010

Background:

Advances in multiparameter flow cytometry (FCM) now allow for the independent detection of larger numbers of fluorochromes on individual cells, generating data with increasingly higher dimensionality. The increased complexity of these data has made it difficult to identify cell populations from high‐dimensional FCM data using traditional manual gating strategies based on single‐color or two‐color displays.

Methods:

To address this challenge, we developed a novel program, FLOCK (FLOw Clustering without K), that uses a density‐based clustering approach to algorithmically identify biologically relevant cell populations from multiple samples in an unbiased fashion, thereby eliminating operator‐dependent variability.

Results:

FLOCK was used to objectively identify seventeen distinct B‐cell subsets in a human peripheral blood sample and to identify and quantify novel plasmablast subsets responding transiently to tetanus and other vaccinations in peripheral blood. FLOCK has been implemented in the publically available Immunology Database and Analysis Portal—ImmPort (http://www.immport.org)—for open use by the immunology research community.

Conclusions:

FLOCK is able to identify cell subsets in experiments that use multiparameter FCM through an objective, automated computational approach. The use of algorithms like FLOCK for FCM data analysis obviates the need for subjective and labor‐intensive manual gating to identify and quantify cell subsets. Novel populations identified by these computational approaches can serve as hypotheses for further experimental study. © 2010 International Clinical Cytometry Society
Monoclonal B cell lymphocytosis: Clinical and population perspectives
Authors: Caporaso Neil E. , Marti Gerald E. , Landgren Ola , Azzato Elizabeth , Weinberg J. Brice , Goldin Lynn , Shanafelt Tait
Published: September 2010

Monoclonal B Cell Lymphocytosis (MBL) refers to clones of CLL‐like cells that exhibit CLL characteristics that fall short of the numbers required for CLL diagnosis. Data from large CLL kindreds document increased prevalence of MBL suggesting a genetic contribution to its etiology. The molecular features that favor progression of MBL to CLL are poorly understood but an elevated B‐cell count is a risk factor for progression. An important consideration when evaluating volunteers from CLL families who are willing to donate bone marrow is that MBL be ruled out since the MBL donor clone could result in a second CLL in the recipient. Further studies of MBL are needed to identify the molecular features and how they evolve during progression. Published 2010 Wiley‐Liss, Inc.
A computer simulation for exploring the detection of monoclonal B‐cell lymphocytosis by flow cytometry
Authors: Champion Patrick D.
Published: September 2010

Background:

Monoclonal B‐cell lymphocytosis (MBL) is defined by the presence of monoclonal B‐cells in peripheral blood in the absence of hematologic disease. MBL is detected by flow cytometry with increasing frequency as the number of B‐cells acquired increases.

Methods:

Computer simulations in R language were used to examine the impact of increasing the number of B‐cells acquired on the sensitivity of detecting MBL and to explore the possibility of detecting distinct B‐cell clones among polyclonal B‐cell populations.

Results:

With simulated populations containing 0.1%–1.0% monoclonal B‐cells, the number of clonal B‐cells detected showed a normal distribution in the upper range of clonal cells acquired and more nearly log‐normal as the distributions became bounded by 0. The distributions peaked around the clonal prevalence. The detection of MBL increased sharply with a small increase in the total number of B‐cells acquired when the number of clonal cells acquired was near the MBL cutoff point. MBL could be detected in log‐normally distributed polyclonal B‐cell populations.

Conclusions:

Sampling variability in detecting monoclonal B‐cells can be investigated through simulation. The observed population prevalence of MBL can be approximated with reasonable assumptions about the distribution of clonotypes in the circulating B‐cell compartment. © 2010 International Clinical Cytometry Society
Effect of nortriptyline on cytosolic Ca2+ regulation and viability in PC3 human prostate cancer cells
Authors: Pan Chih‐Chuan , Shaw Chen‐Fu , Huang Jong‐Khing , Kuo Chun‐Chi , Kuo Daih‐Huang , Shieh Pochuen , Lu Ti , Chen Wei‐Chuan , Ho Chin‐Man , Jan Chung‐Ren
Published: September 2010

The effect of nortriptyline, a tricyclic antidepressant, on Ca2+ regulation and viability in human prostate cancer cells (PC3) is unclear. The present study examined whether nortriptyline altered basal [Ca2+]i levels in suspended PC3 cells using fura‐2 as a Ca2+‐sensitive fluorescent probe. Nortriptyline (50–500 µM) increased [Ca2+]i in a concentration‐dependent fashion. The Ca2+ signal was partially reduced by removing extracellular Ca2+, indicating that Ca2+ entry and release both contributed to the [Ca2+]i rise. Nortriptyline induced Mn2+ influx, leading to quench of fura‐2 fluorescence, suggesting Ca2+ influx. This Ca2+ influx was inhibited by activation of protein kinase C, but not by inhibition of L‐type Ca2+ channels. In Ca2+‐free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitor, thapsigargin nearly abolished nortriptyline‐induced Ca2+ release. Conversely, pretreatment with nortriptyline greatly reduced the inhibitor‐induced [Ca2+]i rise, suggesting that nortriptyline released Ca2+ from the endoplasmic reticulum. Inhibition of phospholipase C did not change the nortriptyline‐induced [Ca2+]i rise. Nortriptyline at a concentration of 10 µM increased viability in a Ca2+‐independent manner. At 50 µM, nortriptyline killed 45% of cells. Nortriptyline at 10 µM did not induce apoptosis, but at 50 µM induced significant apoptosis measured by propidium iodide staining. Together, in PC3 cells, nortriptyline induced [Ca2+]i rises by causing the phospholipase C‐independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via the protein kinase C‐sensitive pathway. Nortriptyline also induced both cell proliferation and death in a concentration‐dependent manner. Apoptosis was involved in the cell death. Drug Dev Res 71:323–330, 2010. © 2010 Wiley‐Liss, Inc.
Glucose effectiveness and insulin sensitivity measurements derived from the non‐insulin‐assisted minimal model and the clamp techniques are concordant
Authors: Henriksen Jan Erik , Alford Frank , Ward Glenn , Thye‐Rønn Peter , Levin Klaus , Hother‐Nielsen Ole , Rantzau Christian , Boston Ray , Beck‐Nielsen Henning
Published: September 2010

Background

We investigated the concordance between glucose effectiveness (SG) and insulin sensitivity (SI), derived from the unmodified dynamic non‐insulin‐assisted intravenous glucose tolerance test (IVGTT) implemented by SGMM and SIMM; simulation analysis and modelling/conversational interaction (SAAM/CONSAM) versus the eu/hyperglycaemic basal insulinaemic and the euglycaemic hyperinsulinaemic clamp (SGCLAMP and SICLAMP).

Methods

Twenty‐seven of 30 normoglycaemic subjects completed a (1) euglycaemic hyperinsulinaemic clamp, (2) 6‐h eu/hyperglycaemic near‐normoinsulinaemic pancreatic clamp with hyperglycaemia present over the final 2 h of the clamp (Day 2 study), (3) identical clamp to (2) but with euglycaemia maintained over the entire 6 h (Day 3 study) and (4) IVGTT. SGCLAMP was calculated in two ways based on data from study (2) alone (Day 2 SGCLAMP210–240′) or from data from study day (2) and (3) (Day 2–3 SGCLAMP330–360′).

Results

SGMM was unrelated to the magnitude of endogenous insulin release (AIR). The single‐day (Day 2) and two‐day (Day 2 and 3) SGCLAMP protocols correlated (r = 0.72, p = 0.003), but SGCLAMP210–240′ was significantly (p = 0.001) higher than SGCLAMP330–360′. Employing the Day 2 and 3 SGCLAMP protocol, the whole body SGCLAMP330–360′ was similar to SGMM (1.80 ± 0.82 versus 1.73 ± 0.58 dL/min) and correlated (r = 0.45, p < 0.02). SGCLAMP210–240′ did not correlate with SGMM (r = 0.24). SIMM and SICLAMP were similar (0.093 ± 0.060 versus 0.087 ± 0.029 dL/min per mU/L) and correlated (r = 0.76, p < 0.001).

Conclusions

The time‐dependent increase in glucose disposal observed during a prolonged 6‐h clamp significantly influences the estimation of SGCLAMP, and significant concordance coefficients are observed between SGMM, and SGCLAMP330–360′, and SIMM and SICLAMP. Copyright © 2010 John Wiley & Sons, Ltd.
Characterization of immunoglobulin heavy chain knockout rats
Authors: Ménoret Séverine , Iscache Anne‐L. , Tesson Laurent , Rémy Séverine , Usal Claire , Osborn Michel J. , Cost Gregory J. , Brüggemann Marianne , Buelow Roland , Anegon Ignacio
Published: September 2010

The rat is a species frequently used in immunological studies but, until now, there were no models with introduced gene‐specific mutations. In a recent study, we described for the first time the generation of novel rat lines with targeted mutations using zinc‐finger nucleases. In this study, we compare immune development in two Ig heavy‐chain KO lines; one with truncated Cμ and a new line with removed JH segments. Rats homozygous for IgM mutation generate truncated Cμ mRNA with a de novo stop codon and no Cγ mRNA. JH‐deletion rats showed undetectable mRNA for all H‐chain transcripts. No serum IgM, IgG, IgA and IgE were detected in these rat lines. In both lines, lymphoid B‐cell numbers were reduced >95% versus WT animals. In rats homozygous for IgM mutation, no Ab‐mediated hyperacute allograft rejection was encountered. Similarities in B‐cell differentiation seen in Ig KO rats and ES cell‐derived Ig KO mice are discussed. These Ig and B‐cell‐deficient rats obtained using zinc‐finger nucleases‐technology should be useful as biomedical research models and a powerful platform for transgenic animals expressing a human Ab repertoire.
What are regulatory B cells?
Authors: Gray David , Gray Mohini
Published: September 2010

B cells are now acknowledged to play multiple roles in the immune response, in addition to making antibodies. Their role in regulating T‐cell responses during inflammation has come into focus recently. Thus, IL‐10 production by B cells has been shown to be important in limiting auto‐reactive and pathogen‐driven immune pathology; however, the exact identity of the regulatory B cells remains elusive; do they belong to a committed subset or can all B cells regulate given the appropriate inducing stimuli? A study in this issue of the European Journal of Immunology provides insight into the IL‐10‐producing B cells in humans, suggesting that many B cells have the capacity to make IL‐10 when optimally stimulated via the BCR and TLR9. Despite producing significant amounts of inflammatory cytokines as well, these B cells suppress T‐cell proliferation. This Commentary places this study in the context of what we think we know about regulatory B cells and more importantly highlights the questions we still need to answer.
On the origin of cattle: How aurochs became cattle and colonized the world
Authors: Ajmone‐Marsan Paolo , Garcia José Fernando , Lenstra Johannes A.
Published: September 2010

Since their domestication in the Neolithic, cattle have belonged to our cultural heritage. The reconstruction of their history is an active field of research1 that contributes to our understanding of human history. Archeological data are now supplemented by analyses of modern and ancient samples of cattle with DNA markers of maternal, paternal, or autosomal inheritance. The most recent genetic data suggest that maternal lineages of taurine cattle originated in the Fertile Crescent with a possible contribution of South‐European wild cattle populations, while zebu cattle originate from the Indus Valley. Subsequently, cattle accompanied human migrations, which led to the dispersal of domestic cattle of taurine, indicine, or mixed origin over Asia, Africa, Europe, and the New World. This has resulted in their adaptation to different environments and considerable variation in appearance and performance. More recently, rational management of breeding led to international movements of sires, which again changed the global patterns of genetic diversity.
Inhibition of inducible nitric oxide synthase reverses the loss of functional hyperemia in diabetic retinopathy
Authors: Mishra Anusha , Newman Eric A.
Published: September 2010

Neuronal activity leads to arteriole dilation and increased blood flow in retinal vessels. This response, termed functional hyperemia, is diminished in the retinas of diabetic patients, possibly contributing to the development of diabetic retinopathy. The mechanism responsible for this loss is unknown. Here we show that light‐evoked arteriole dilation was reduced by 58% in a streptozotocin‐induced rat model of type 1 diabetes. Functional hyperemia is believed to be mediated by glial cells and we found that glial‐evoked vasodilation was reduced by 60% in diabetic animals. The diabetic retinas showed neither a decrease in the thickness of the retinal layers nor an increase in neuronal loss, although signs of early glial reactivity and an upregulation of inducible nitric oxide synthase (iNOS) were detected. Inhibition of iNOS restored both light‐ and glial‐evoked dilations to control levels. These findings suggest that high NO levels resulting from iNOS upregulation alters glial control of vessel diameter and may underlie the loss of functional hyperemia observed in diabetic retinopathy. Restoring functional hyperemia by iNOS inhibition may limit the progression of retinopathy in diabetic patients. © 2010 Wiley‐Liss, Inc.
Soil pore characteristics of evergreen and deciduous forests of the tropical monsoon region in Cambodia
Authors: Toriyama Jumpei , Ohta Seiichi , Araki Makoto , Kosugi Ken'ichirou , Nobuhiro Tatsuhiko , Kabeya Naoki , Shimizu Akira , Tamai Koji , Kanzaki Mamoru , Chann Sophal
Published: September 2010

Both evergreen and deciduous forests (Efs and Dfs) are widely distributed under similar climatic conditions in tropical monsoon regions. To clarify the hydraulic properties of the soil matrix in different forest types and their effects on soil water storage capacity, the soil pore characteristics (SPC) were investigated in Ef and Df stands in three provinces in Cambodia. Soils in the Ef group were characterized in common by large amounts of coarse pores with moderate pore size distribution and the absence of an extremely low Ks at shallow depths, compared to Df group soils. The mean available water capacity of the soil matrix (AWCsm) for all horizons of the Ef and Df group soils was 0·107 and 0·146 m3 m−3, respectively. The mean coarse pore volume of the soil matrix (CPVsm) in the Ef and Df groups was 0·231 and 0·115 m3 m−3, respectively. A water flow simulation using a lognormal distribution model for rain events in the early dry season indicated that variation in SPC resulted in a larger increase in available soil water in Ef soils than in Df soils. Further study on deeper soil layers in Ef and each soil type in Df is necessary for the deeper understanding of the environmental conditions and the hydrological modelling of each forest ecosystem. Copyright © 2010 John Wiley & Sons, Ltd.
Id3 modulates cellular localization of bHLH Ptf1‐p48 protein
Authors: Dufresne Marlène , Clerc Pascal , Dieng Madieng , Edir Anissa , Couvelard Anne , Delisle Marie‐Bernadette , Fourmy Daniel , Gigoux Véronique
Published: September 2010

Ptf1‐p48 is a pancreas‐specific bHLH transcriptional protein, which, in the normal adult pancreas, shows a restricted expression in acinar cells where it is predominantly localized in the nucleus and activates the transcription of exocrine‐specific genes. Ptf1‐p48 partners with two proteins to form the PTF1 active complex: a bHLH E‐protein and suppressor of hairless RBP‐J. Cytoplasmic mislocalization of Ptf1‐p48 has been reported in pancreatic pathologies, suggesting its contribution in the early steps of pancreatic carcinogenesis. The aim of the our work was to elucidate the mechanisms regulating Ptf1‐p48 subcellular localization. We hypothesized a role of Id proteins acting in a dominant‐negative fashion by heterodimerizing with bHLH proteins. We reproduced Ptf1‐p48 cytoplasmic mislocalization in acinar AR4‐2J cells and demonstrated that a proliferative signal elicited by gastrin leads to increases in Id3 protein expression and levels of Id3/E47 and Id3/Ptf1‐p48 interactions, and a decrease in the level of E47/Ptf1‐p48 interaction. By contrast, Id3 silencing reversed the cytoplasmic mislocalization of Ptf1‐p48 induced by gastrin. As E47 is responsible for the nuclear import of the PTF1 complex, disruption of this complex via Id3 interactions with both E47 and Ptf1‐p48 appears to induce cytoplasmic mislocalization of Ptf1‐p48. We then found that Ptf1‐p48 is either absent or mislocalized in the cytoplasm and Id3 is overexpressed in human and murine pancreatic preneoplastic lesions. Our data provide novel insight into the regulation of Ptf1‐p48 function and provide evidence that Ptf1‐p48 cytoplasmic mislocalization and Id3 overexpression are early events in pancreatic cancer progression.
Identification of p10 as a neurotoxic product generated from the proteolytic cleavage of the neuronal Cdk5 activator
Authors: Chew Jenny , Chen Minghui Jessica , Lee Alan Yiu‐Wah , Peng Zhao Feng , Chong Kevin Wai Yin , He Lisheng , Bay Boon Huat , Ng Jian Ming Jeremy , Qi Robert Z. , Cheung Nam Sang
Published: September 2010

The involvement of cyclin‐dependent kinase‐5 (Cdk5) and p25, the proteolytic fragment of activator p35, has long been implicated in the development of neuron‐fibrillary tangles (NFTs), a hallmark of Alzheimer's disease (AD). Findings in this area over the past decade have been highly controversial and inconclusive. Here we report unprecedented detection of endogenous p10, the smaller proteolytic fragment of the Cdk5 activator p35 in treated primary cortical neurons that underwent significant apoptosis, triggered by proteasome inhibitors MG132 and lactacystin, and protein kinase inhibitor staurosporine (STS). p10 appeared exclusively in the detergent‐resistant fraction made up of nuclear matrix, membrane‐bound organelles, insoluble membrane proteins, and cytoskeletal components. Intriguingly, transient overexpression of p10 in neural cells induced apoptotic morphologies, suggesting that p10 may play an important role in mediating neuronal cell death in neurodegenerative diseases. We demonstrated for the first time that p10‐mediated apoptosis occurred via a caspases‐independent pathway. Furthermore, as p10 may contain the myristoylation signal for p35 which is responsible for binding p35 to several intracellular components and the membrane, all in all these novel results present that the accumulation of p10 to the detergent‐insoluble fraction may be a crucial pathological event to triggering neuronal cell death. J. Cell. Biochem. 111: 1359–1366, 2010. © 2010 Wiley‐Liss, Inc.
Berberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: The cellular mechanism
Authors: Wang Ning , Feng Yibin , Zhu Meifen , Tsang Chi‐Man , Man Kwan , Tong Yao , Tsao Sai‐Wah
Published: September 2010

Extensive studies have revealed that berberine, a small molecule derived fromCoptidis rhizoma(Huanglian in Chinese) and many other plants, has strong anti‐tumor properties. To better understand berberine‐induced cell death and its underlying mechanisms in cancer, we examined autophagy and apoptosis in the human hepatic carcinoma cell lines HepG2 and MHCC97‐L. The results of this study indicate that berberine can induce both autophagy and apoptosis in hepatocellular carcinoma cells. Berberine‐induced cell death in human hepatic carcinoma cells was diminished in the presence of the cell death inhibitor 3‐methyladenine, or following interference with the essential autophagy gene Atg5. Mechanistic studies showed that berberine may activate mitochondrial apoptosis in HepG2 and MHCC97‐L cells by increasing Bax expression, the formation of permeable transition pores, cytochrome C release to cytosol, and subsequent activation of the caspases 3 and 9 execution pathway. Berberine may also induce autophagic cell death in HepG2 and MHCC97‐L cells through activation of Beclin‐1 and inhibition of the mTOR‐signaling pathway by suppressing the activity of Akt and up‐regulating P38 MAPK signaling. This is the first study to describe the role of Beclin‐1 activation and mTOR inhibition in berberine‐induced autophagic cell death. These results further demonstrate the potential of berberine as a therapeutic agent in the emerging list of cancer therapies with novel mechanisms. J. Cell. Biochem. 111: 1426–1436, 2010. © 2010 Wiley‐Liss, Inc.
Morphological and molecular pathology of CCL4‐induced hepatic fibrosis in connexin43‐deficient mice
Authors: Cogliati Bruno , Da silva Tereza Cristina , Aloia Thiago Pinheiro Arrais , Chaible Lucas Martins , Real‐Lima Mirela Aline , Sanches Daniel Soares , Matsuzaki Patrícia , Hernandez‐Blazquez Francisco Javier , Dagli Maria Lúcia Zaidan
Published: September 2010

Gap junction channels, formed by connexins (Cx), are involved in the maintenance of tissue homeostasis, cell growth, differentiation, and development. Several studies have shown that Cx43 is involved in the control of wound healing in dermal tissue. However, it remains unknown whether Cx43 plays a role in the control of liver fibrogenesis. Our study investigated the roles of Cx43 heterologous deletion on carbon tetrachloride (CCl4)‐induced hepatic fibrosis in mice. We administered CCl4 to both Cx43‐deficient (Cx43+/−) and wild‐type mice and examined hepatocellular injury and collagen deposition by histological and ultrastructural analyses. Serum biochemical analysis was performed to quantify liver injury. Hepatocyte proliferation was analyzed immunohistochemically. Protein and messenger RNA (mRNA) expression of liver connexins were evaluated using immunohistochemistry as well as immunoblotting analysis and quantitative real‐time PCR. We demonstrated that Cx43+/− mice developed excessive liver fibrosis compared with wild‐type mice after CCl4‐induced chronic hepatic injury, with thick and irregular collagen fibers. Histopathological evaluation showed that Cx43+/− mice present less necroinflammatory lesions in liver parenchyma and consequent reduction of serum aminotransferase activity. Hepatocyte cell proliferation was reduced in Cx43+/− mice. There was no difference in Cx32 and Cx26 protein or mRNA expression in fibrotic mice. Protein expression of Cx43 increased in CCl4‐treated mice, although with aberrant protein location on cytoplasm of perisinusoidal cells. Our results demonstrate that Cx43 plays an important role in the control and regulation of hepatic fibrogenesis. Microsc. Res. Tech., 2011. © 2010 Wiley‐Liss, Inc.
Hip screw migration testing: First results for hip screws and helical blades utilizing a new oscillating test method
Authors: Born Christopher T. , Karich Bernhard , Bauer Christoph , von Oldenburg Geert , Augat Peter
Published: September 2010

Despite continued improvement in the methods and devices used to treat intertrochanteric fractures, there remains an unacceptable amount of failures. The cut‐out rate for hip screws has been recorded up to 8.3%. To evaluate the migration of different implants under physiological loads, a multiplanar biomechanical test method for hip screws was developed, the first to incorporate a simulation of the human gait cycle by an oscillating flexion/extension movement of the test device. The new method was used to compare different hip screw and blade designs with respect to their directional migration resistance. The test method generated failure modes that were consistent with those observed clinically. Under cyclic loading, the hip screws migrated predominantly in a cephalad direction. In contrast, the helical blades exhibited a distinct migration in their axial direction. The Gamma3 hip screw design showed a significantly higher migration resistance compared with other screw and helical blade designs. The results demonstrate the ability of hip screws to significantly reduce axial migration and prevent cut‐out under simulated walking loads. Further, the new multiplanar test method creates a physiological environment that can be used to optimize designs for intertrochanteric fracture fixation. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:760–766, 2011
Block method of human temporal bone removal: A technical modification to permit rapid removal
Authors: Walvekar Rohan R. , Harless Lucas D. , Loehn Bridget C. , William Swartz
Published: September 2010

Objectives/Hypothesis:

To describe a technical modification to the block method (BM) of harvesting human cadaveric temporal bones for otolaryngology resident education and training.

Study Design:

Human cadaveric study.

Methods:

Human cadavers previously dissected by medical students in a professional health science program were identified as potential candidate specimens for temporal bone removal. Cadaveric heads were prepared for temporal bone harvesting by excising the calvarium and brain via standard techniques. A reciprocating saw was used to make four bone cuts to harvest two temporal bone specimens.

Results:

Temporal bone specimens could be harvested using only four bone cuts to release both temporal bones from one human cadaver as opposed to four bone cuts for a single temporal bone per the traditional BM. All temporal bones were inspected and found to have all the anatomical landmarks necessary for resident education and training intact.

Conclusions:

The modified BM for temporal bone removal is a rapid, efficient, and reproducible method of harvesting two complete and intact temporal bones per cadaver with fewer bone cuts as compared to the traditional BM. Laryngoscope, 2010
Effect of eradication of Helicobacter pylori in children with chronic immune thrombocytopenia: A prospective, controlled, multicenter study
Authors: Russo Giovanna , Miraglia Vito , Branciforte Francesca , Matarese Sofia Maria Rosaria , Zecca Marco , Bisogno Gianni , Parodi Emilia , Amendola Giovanni , Giordano Paola , Jankovic Momcilo , Corti Annalisa , Nardi Margherita , Farruggia Piero , Battisti Laura , Baronci Carlo , Palazzi Giovanni , Tucci Fabio , Ceppi Stefania , Nobili Bruno , Ramenghi Ugo , De Mattia Domenico , Notarangelo Lucia ,   the AIEOP‐ITP Study Group
Published: September 2010

Background

The eradication of Helicobacter pylori has been associated with remission of immune thrombocytopenia (ITP) in approximately half of eradicated patients. Data on children are limited to small case series.

Procedure

Children from 16 centers in Italy, who were less than 18 years of age and diagnosed with chronic ITP (cITP), were screened for H. pylori infection. Positive patients underwent standard triple therapy with amoxicillin, clarithromycin, and omeprazole. The eradication response was defined as follows: complete response, platelet (PLT) count ≥150 × 109/L; partial response, PLT count of at least 50 × 109/L; no response, PLT count <50 × 109/L.

Results

Of 244 screened patients, 50 (20%) had H. pylori infection, 37 of which received eradication therapy and completed follow‐up. Eradication was successful in 33/37 patients (89%). PLT recovery was demonstrated in 13/33 patients after eradication (39%), whereas spontaneous remission was observed in 17/166 (10%) H. pylori‐negative patients (P < 0.005). Responders more often required second line eradication (9/13), whereas a second cycle was required in 3/20 non‐responders (P < 0.005).

Conclusions

Among the large cohort of patients, those who underwent successful H. pylori eradication showed a significantly higher PLT response. Therefore, it may be appropriate to look for H. pylori and eventually eradicate it in children with cITP. Pediatr Blood Cancer 2011;56:273–278. © 2010 Wiley‐Liss, Inc.
Prospective evaluation of legal difficulties and quality of life in adult survivors of childhood cancer
Authors: Olson Robert , Hung Gabe , Bobinski Mary Anne , Goddard Karen
Published: September 2010

Background

Adult survivors of childhood cancer (ASCC), especially those of the central nervous system (CNS), have increased risks of educational and social difficulties. It is therefore hypothesized they are more likely to encounter legal difficulties (LDs), such as workplace discrimination and disability insurance denials, which may negatively affect their quality of life (QoL).

Procedure

We developed a survey to collect information on patients' legal needs. QoL was assessed using the Functional Assessment of Cancer Therapy (FACT).

Results

We prospectively approached 112 ASCC, 111 (99.1%) of whom completed the survey. The median age of respondents was 7 years at diagnosis and 31 years at survey completion. CNS tumors were the most common malignancy (32.4%). LDs were common overall (40.7%), though more prevalent in patients with CNS versus non‐CNS tumors (58.6% vs. 32.3%; P = 0.023). The most prevalent LD was workplace discrimination (58.3%). On multivariate analysis, CNS tumor was the only variable significantly associated with LDs (OR = 4.49, P = 0.041). Individuals with LDs had lower QoL scores compared to those without LDs (79.96 versus 91.83 on the FACT; P = 0.005). On multivariate analysis, individuals with LDs had lower QoL scores (14.95 points lower on the FACT), which is both clinically and statistically significant (P = 0.047).

Conclusions

Legal difficulties are common in adult survivors of childhood cancer, especially those with brain tumors. Furthermore, individuals with legal difficulties have worse quality of life. Research is needed to develop effective and accessible legal resource programs. Pediatr Blood Cancer 2011;56:439–443. © 2010 Wiley‐Liss, Inc.
Height impairment after lower dose cranial irradiation in children with acute lymphoblastic leukemia
Authors: Paulino Arnold C. , Jhaveri Pavan , Dreyer Zoann , Teh Bin S. , Okcu M. Fatih
Published: September 2010

Purpose

The purpose of this study is to determine whether height measurements are affected by cranial radiation doses of 12–18 Gy.

Patients and Methods

From 1997 to 2007, 23 children received cranial RT for T‐cell or pre‐B‐cell acute lymphoblastic leukemia (ALL). Dose fractionation schemes included 18 Gy in 9 fractions (n = 8), 18 Gy in 10 fractions (n = 5), 12.6 Gy in 7 fractions (n = 6), and 12 Gy in 8 fractions (n = 4). These patients were matched and compared to a control group of 23 patients who had ALL but no cranial RT. Height z‐scores at diagnosis and last follow‐up were compared using the paired Student's t‐test. Differences in z‐scores according to host and treatment parameters were compared using the unpaired Student's t‐test. Median follow‐up for irradiated patients was 63.5 months while for unirradiated patients was 91 months.

Results

The mean z‐scores at initial diagnosis and last follow‐up were 0.14 and −0.48 for patients receiving 12–12.6 Gy (P = 0.016), −0.16 and −0.89 for 18 Gy (P = 0.003), and 0.34 and 0.22 for no RT (P = 0.62). For children receiving RT, the mean difference in z‐scores at initial diagnosis and last follow‐up was −0.67 while for those not receiving RT, it was −0.10 (P = 0.043).

Conclusion

Children receiving 12–18 Gy cranial RT for ALL were found to have height impairment compared to those not receiving RT. Pediatr Blood Cancer 2011;56:279–281. © 2010 Wiley‐Liss, Inc.
Childhood cancer trends in a western Canadian province: A population‐based 22‐year retrospective study
Authors: Rosychuk Rhonda J. , Witol Adrienne , Stobart Kent
Published: September 2010

Objectives

The objective of this study was to describe children and youth <20 years of age diagnosed with malignant cancer in Alberta, Canada over 22 years. We consider both temporal and geographical variations.

Procedure

The Alberta Cancer registry was used to extract information on cancer diagnoses during April 1, 1982, and March 31, 2004. Data extracted included gender, age at diagnosis, diagnosis, and geographic information. Population data were also obtained and analyses included descriptive summaries, rates, and cluster detection tests.

Results

During 22 fiscal years, 2,758 Alberta children and youth were diagnosed with malignant cancer. The average age of diagnosis was 9.6 years. The most common diagnoses were leukemia (24.8%), central nervous system (16.7%), lymphoma (15.8%), and other epithelial neoplasm and melanoma (11.2%). The number of malignant cases varied over year with crude rates of 13.4 per 100,000 in 1982/1983 to 17.3 per 100,000 in 2003/2004. Variation was also seen over diagnosis sub‐group and geographic region.

Conclusions

Although a relatively rare number of children and youth in Alberta were diagnosed with cancer during the study period, there were suggestions that an increase incidence in childhood cancer occurred in later years and some geographic areas have more cases than expected by chance. Further study is required to see if emerging trends continue and explain higher rate areas. Pediatr Blood Cancer. 2010;55:1348–1355. © 2010 Wiley‐Liss, Inc.