bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity of ketoconazole after taxane‐based chemotherapy in castration‐resistant prostate cancer
Authors: Nakabayashi Mari , Oh William K. , Jacobus Susanna , Regan Meredith M. , Taplin Mary‐Ellen , Kantoff Philip W. , Rosenberg Jonathan E. 
Published: October 2009

Study Type – Therapy (case series)Level of Evidence 4OBJECTIVETo assess the efficacy of the androgen‐synthesis inhibitor ketoconazole as a secondary hormonal therapy in patients with castration‐resistant prostate cancer (CRPC) previously treated with chemotherapy, as persistent androgens appear to play a role in the development and maintenance of CRPC.PATIENTS AND METHODSWe retrospectively identified 34 patients with CRPC who were treated with ketoconazole as a secondary hormonal therapy after paclitaxel‐ or docetaxel‐based chemotherapy for CRPC. They were treated with ketoconazole 200–400 mg three times daily with or without hydrocortisone. Patients with previous use of ketoconazole were excluded. Half the patients had received estramustine as part of their chemotherapy regimen. The primary endpoint was the proportion of patients with a decline of ≥50% in their prostate‐specific antigen (PSA) level. PSA progression was defined by the PSA Working Group 1 Criteria.RESULTSEight of the 32 evaluable patients (25%) had a PSA decline of ≥50%. The median time to progression (TTP) was 3 months (95% confidence interval, 1.2–5.4). A history of previous response to taxane‐based chemotherapy was not associated with the response to ketoconazole. However, previous use of oestrogens for CRPC was significantly associated with a shorter TTP on ketoconazole (1.5 vs 10.2 months; P = 0.03).CONCLUSIONSKetoconazole has moderate activity as secondary hormonal therapy in patients with CRPC previously treated with taxane‐based chemotherapy, although the TTP was short. Previous treatment with oestrogenic therapy is associated with a shorter TTP.
Analysis of four prevalent filaggrin mutations (R501X, 2282del4, R2447X and S3247X) in Austrian and German patients with atopic dermatitis
Authors: Greisenegger EK , Novak N , Maintz L , Bieber T , Zimprich F , Haubenberger D , Gleiss A , Stingl G , Kopp T , Zimprich A 
Published: October 2009

AbstractBackground  Recently, mutations in the filaggrin gene (FLG) have been shown to be a major predisposing factor for atopic dermatitis (AD).Objective  In this study, we evaluated the influence of four prevalent mutations (R501X, 2282del4, R2447X and S3247X) in a large cohort of 462 Austrian and German AD patients and in 402 control individuals.Results  We found a strong association of the FLG mutations with AD. Subgroup analysis revealed a significantly higher proportion of patients with an early age of disease onset and significantly higher median serum IgE levels among mutation carriers.Furthermore, we observed an overrepresentation of null alleles in AD patients with concomitant asthma compared with those without this co‐morbidity.Conclusion  Our data confirm and extend the knowledge of the influence of FLG mutations in AD.
An Italian shared dermatological and rheumatological proposal for the use of biological agents in psoriatic disease
Authors: Marchesoni A , Altomare G , Matucci‐Cerinic M , Balato N , Olivieri I , Salvarani C , Lotti T , Scarpa R , Vena GA , Valesini G , Giannetti A 
Published: October 2009

AbstractBackground  As psoriatic disease (PD) is a condition characterized by the combination of inflammatory skin (psoriasis) and osteo‐articular manifestations (psoriatic arthritis), its treatment should cover both its clinical components.Objective  The objective of this study was to propose a flexible framework for the use of biological agents in PD.Methods  The proposal was drawn up by a group of dermatologists and rheumatologist expert in PD and was based on existing evidence and personal opinion.Results  The three TNF‐α inhibitors (adalimumab, etanercept, infliximab) are effective in all of the psoriatic manifestations and should be used in the case of moderate/severe disease refractory to systemic treatment with non‐biological drugs. We propose the following definitions of moderate/severe disease: PASI > 10 or BSA > 10 or DLQI > 10 for plaque‐psoriasis; BSA ≥ 10 or DLQI ≥ 10 for the other psoriatic skin lesions; DLQI ≥ 10 or meaningful values of the NAPSI or mNAPSI for psoriatic nail involvement; ≥ 1 inflamed joint + patient global VAS34 + physician's judgement or arthritic joint deformities or radiographic joint damage plus ≥ 5 inflamed small joints or ≥ 1 large joints for peripheral joint involvement; ≥ 1 digit with dactylitis and ≥ 1 enthesitic sites + patient global VAS34 + physician's judgement for dactylitis and enthesitis. BASDAI ≥ 4 + physician's judgement for spondylitis; recurrent flares or risk of developing irreversible damage for uveitis. Other assessment instruments can be used if the physician is more familiar with them and if they have been validated.Conclusion  We provide a shared dermatological and rheumatological proposal for the use of biological agents in PD.
The evolution of the land plant life cycle
Authors: Niklas Karl J. , Kutschera Ulrich 
Published: October 2009

SummaryThe extant land plants are unique among the monophyletic clade of photosynthetic eukaryotes, which consists of the green algae (chlorophytes), the charophycean algae (charophytes), numerous groups of unicellular algae (prasinophytes) and the embryophytes, by possessing, firstly, a sexual life cycle characterized by an alternation between a haploid, gametophytic and a diploid, sporophytic multicellular generation; secondly, the formation of egg cells within multicellular structures called archegonia; and, thirdly, the retention of the zygote and diploid sporophyte embryo within the archegonium. We review the developmental, paleobotanical and molecular evidence indicating that: the embryophytes descended from a charophyte‐like ancestor; this common ancestor had a life cycle with only a haploid multicellular generation; and the most ancient (c. 410 Myr old) land plants (e.g. Cooksonia, Rhynia and Zosterophyllum) had a dimorphic life cycle (i.e. their haploid and diploid generations were morphologically different). On the basis of these findings, we suggest that the multicellular reproductive structures of extant charophytes and embryophytes are developmentally homologous, and that those of the embryophytes evolved by virtue of the co‐option and re‐deployment of ancient algal homeodomain gene networks.

Contents

Summary
27

I.
Introduction
28

II.
Developmental constraint or a phyletic legacy?
29

III.
Green plant phylogeny
29

IV.
The ancestral green plant life cycle
31

V.
Haplobiontic or diplobiontic life cycles?
32

VI.
Pseudo‐archegonia, plasmodesmata, and parenchyma
33

VII.
Genomic re‐deployment and embryophyte reproduction
35

VIII.
Developmental homologies?
35

IX.
Isomorphic or dimorphic?
36

X.
Conclusions
38

Acknowledgements
39

References
39
Angelman syndrome: Current understanding and research prospects
Authors: Dan Bernard 
Published: October 2009

SummaryAngelman syndrome is a neurogenetic disorder characterized by developmental delay, severe intellectual disability, absent speech, exuberant behavior with happy demeanor, motor impairment, and epilepsy, due to deficientUBE3Agene expression that may be caused by various abnormalities of chromosome 15. Recent findings in animal models demonstrated altered dendritic spine formation as well as both synaptic [including γ‐aminobutyric acid (GABA)AandN‐methyl‐d‐aspartate (NMDA) transmission] and nonsynaptic (including gap junction) influences in various brain regions, including hippocampus and cerebellar cortex. Reversal of selected abnormalities in rescue genetically engineered animal models is encouraging, although it should not be misinterpreted as promising “cure” for affected patients. Much research is still required to fully understand the functional links between lack ofUBE3Aexpression and clinical manifestations of Angelman syndrome. Studies of regulation ofUBE3Aexpression, including imprinting‐related methylation, may point to possibilities of therapeutic upregulation. Understanding relevant roles of the gene product might lead to targeted intervention. Further documentation of brain network dynamics, with particular emphasis on hippocampus, thalamocortical, and cerebellar networks is needed, including in a developmental perspective. There is also a need for further clinical research for improving management of problems such as epilepsy, behavior, communication, learning, motor impairment, and sleep disturbances.
Increased Acid Sphingomyelinase Activity in Peripheral Blood Cells of Acutely Intoxicated Patients With Alcohol Dependence
Authors: Reichel Martin , Greiner Elisabeth , Richter‐Schmidinger Tanja , Yedibela Özlem , Tripal Philipp , Jacobi Andrea , Bleich Stefan , Gulbins Erich , Kornhuber Johannes 
Published: October 2009

Background:  Acid sphingomyelinase (ASM; EC 3.1.4.12) hydrolyses membrane sphingomyelin into the bioactive lipid ceramide and is thus involved in different cellular processes such as differentiation, immunity, or cell death. Activation of ASM has been reported in particular in conjunction with the cellular stress response to several external stimuli, and increased ASM activity was observed in a variety of human diseases. Ethanol‐induced activation of ASM has been observed in different cell culture systems, thus raising the question about the effect of alcohol intoxication in human subjects on ASM activity in vivo.Methods:  We determined ASM activity in peripheral blood mononucleated cells of 27 patients suffering from alcohol dependence. Patients were classified according to their blood alcohol concentration at admission, and ASM activity was determined repeatedly from all patients during alcohol withdrawal.Results:  Acutely intoxicated patients displayed significantly higher ASM activity than patients in early abstinence (Mann–Whitney U test: Z = − 2.6, p = 0.009). ASM activity declined in acutely intoxicated patients to normal values with the transition from the intoxicated state to early abstinence (Wilcoxon test: Z = −2.7, p = 0.007). At the end of withdrawal, ASM activity was significantly increased again compared to the early phase of abstinence in both patient groups (Wilcoxon test: Z = −2.691, p = 0.007 and Z = −2.275, p = 0.023, respectively).Conclusions:  Alcohol‐induced activation of ASM occurs in human subjects and might be responsible for deleterious effects of ethanol intoxication. Chronic alcohol abuse may induce deregulation of sphingomyelin metabolism in general, and this impairment may cause side effects during withdrawal from alcohol.
Galanin Knockout Mice Show Disturbances in Ethanol Consumption and Expression of Hypothalamic Peptides That Stimulate Ethanol Intake
Authors: Karatayev Olga , Baylan Jessica , Weed Valerie , Chang Siyi , Wynick David , Leibowitz Sarah F. 
Published: October 2009

Background:  There is growing evidence suggesting that hypothalamic galanin (GAL), which is known to stimulate intake of a fat‐rich diet, has a role in promoting the consumption of ethanol. The present study further examined this possibility in GAL knockout (GALKO) mice.Methods:  Two groups of female and male GALKO mice, compared to wild‐type (WT) controls, were trained to voluntarily drink increasing concentrations of ethanol, while maintained on lab chow and water. They were examined in terms of their daily ethanol intake and preference, acute consumption of a high‐fat diet, preference for flavored solutions, and expression of different peptides shown to stimulate ethanol intake.Results:  In the GALKO mice compared to WT, the results revealed: (i) a 35 to 45% decrease in ethanol intake and preference, which was evident only at the highest (15%) ethanol concentration, was stronger in female than in male mice, and was seen with comparisons to littermate as well as nonlittermate WT mice; (ii) a 48% decrease in acute intake of a fat‐rich diet, again stronger in female than male mice; (iii) no difference in consumption of sucrose or quinine solutions in preference tests; (iv) a total loss of GAL mRNA in the hypothalamic paraventricular nucleus (PVN) of female and male mice; and (v) a gender‐specific change in mRNA levels of peptides in the perifornical lateral hypothalamus (PFLH), orexin and melanin‐concentrating hormone, which are known to stimulate ethanol and food intake and were markedly decreased in females while increased in males.Conclusions:  These results provide strong support for a physiological role of PVN GAL in stimulating the consumption of ethanol, as well as a fat‐rich diet. Ablation of the GAL gene produced a behavioral phenotype, particularly in females, which may reflect the functional relationship of galanin to ovarian steroids. It also altered the peptides in the PFLH, with their reduced expression contributing to the larger behavioral effects observed in females and their increased expression attenuating these effects in males.
Neuropeptide S Receptor Gene Expression in Alcohol Withdrawal and Protracted Abstinence in Postdependent Rats
Authors: Ruggeri Barbara , Braconi Simone , Cannella Nazzareno , Kallupi Marsida , Soverchia Laura , Ciccocioppo Roberto , Ubaldi Massimo 
Published: October 2009

Background:  Alcoholism is a chronic disease characterized by frequent intoxications followed by withdrawal episodes and relapse to alcohol use. Neuroplastic changes associated with these intoxication and withdrawal cycles are thought to play a key role in disease progression. Recently, it has been shown that neuropeptide S (NPS), a newly deorphanized neuropeptide receptor system, facilitates relapse to alcohol seeking in laboratory animals. Given that a history of ethanol intoxication may increase vulnerability to alcohol addiction, we sought to determine whether NPS receptor (NPSR) gene expression is altered during withdrawal.Methods:  Rats were subjected to 1 week of intoxication by oral alcohol administration. NPSR gene expression was analyzed by in situ hybridization in rats 12 hours and 7 days after the last alcohol administration. To investigate the functional significance of NPSR system adaptation following protracted withdrawal 7 days after intoxication, we tested the anxiolytic‐like properties of NPS in nondependent and postdependent rats using the shock probe defensive burying test (DB).Results:  At both time points, increased NPSR gene expression was observed in several brain areas, including the endopiriform nucleus, the motor cortex, and the medial amygdaloid nucleus. Moderate increases in gene expression were also found in the lateral hypothalamus, paraventricular nucleus, basolateral and central amygdala. Differences from control animals were more pronounced after 7 days of abstinence. The upregulation of the NPSR system at this time point was confirmed by functional data indicating that intracerebroventricular (ICV) NPS administration (0.0, 0.3, and 0.1 nmol/rat) elicits more pronounced anxiolytic effects in postdependent animals than in controls subjected to the electric shock probe DB test.Conclusions:  Neuropeptide S receptor mRNA expression is increased in different brain areas of postdependent rats; as shown in the DB test, this expression change is functionally relevant.
Linkage Analysis of Alcohol Dependence Symptoms in the Community
Authors: Hansell Narelle K. , Agrawal Arpana , Whitfield John B. , Morley Katherine I. , Gordon Scott D. , Lind Penelope A. , Pergadia Michele L. , Montgomery Grant W. , Madden Pamela A. F. , Todd Richard D. , Heath Andrew C. , Martin Nicholas G. 
Published: October 2009

Background:  We have previously identified suggestive linkage for alcohol consumption in a community‐based sample of Australian adults. In this companion paper, we explore the strength of genetic linkage signals for alcohol dependence symptoms.Methods:  An alcohol dependence symptom score, based on DSM‐IIIR and DSM‐IV criteria, was examined. Twins and their nontwin siblings (1,654 males, 2,518 females), aged 21 to 81 years, were interviewed, with 803 individuals interviewed on 2 occasions, approximately 10 years apart. Linkage analyses were conducted on datasets compiled to maximize data collected at either the younger or the older age. In addition, linkage was compared between full samples and truncated samples that excluded the lightest drinkers (approximately 10% of the sample).Results:  Suggestive peaks on chromosome 5p (LODs >2.2) were found in a region previously identified in alcohol linkage studies using clinical populations. Linkage signal strength was found to vary between full and truncated samples and when samples differed only on the collection age for a sample subset.Conclusions:  The results support the finding that large community samples can be informative in the study of alcohol‐related traits.
Red blood cell aging markers during storage in citrate‐phosphate‐dextrose–saline‐adenine‐glucose‐mannitol
Authors: Antonelou Marianna H. , Kriebardis Anastasios G. , Stamoulis Konstantinos E. , Economou‐Petersen Effrosini , Margaritis Lukas H. , Papassideri Issidora S. 
Published: October 2009

BACKGROUND: It has been suggested that red blood cell (RBC) senescence is accelerated under blood bank conditions, although neither protein profile of RBC aging nor the impact of additive solutions on it have been studied in detail.STUDY DESIGN AND METHODS: RBCs and vesicles derived from RBCs in both citrate‐phosphate‐dextrose (CPD)–saline‐adenine‐glucose‐mannitol (SAGM) and citrate‐phosphate‐dextrose‐adenine (CPDA) were evaluated for the expression of cell senescence markers (vesiculation, protein aggregation, degradation, activation, oxidation, and topology) through immunoblotting technique and immunofluorescence or immunoelectron microscopy study.RESULTS: A group of cellular stress proteins exhibited storage time– and storage medium–related changes in their membrane association and exocytosis. The extent, the rate, and the expression of protein oxidation, Fas oligomerization, caspase activation, and protein modifications in Band 3, hemoglobin, and immunoglobulin G were less conspicuous and/or exhibited significant time retardation under storage in CPD‐SAGM, compared to the CPDA storage. There was evidence for the localization of activated caspases near to the membrane of both cells and vesicles.CONCLUSIONS: We provide circumstantial evidence for a lower protein oxidative damage in CPD‐SAGM–stored RBCs compared to the CPDA‐stored cells. The different expression patterns of the senescence markers in the RBCs seem to be accordingly related to the oxidative stress management of the cells. We suggest that the storage of RBCs in CPD‐SAGM might be more alike the in vivo RBC aging process, compared to storage in CPDA, since it is characterized by a slower stimulation of the recognition signaling pathways that are already known to trigger the erythrophagocytosis of senescent RBCs.
Maternal thyroid hormones are transcriptionally active during embryo–foetal development: results from a novel transgenic mouse model
Authors: Nucera Carmelo , Muzzi Patrizia , Tiveron Cecilia , Farsetti Antonella , Regina Federico La , Foglio Benedetta , Shih Shou‐Ching , Moretti Fabiola , Pietra Linda Della , Mancini Francesca , Sacchi Ada , Trimarchi Francesco , Vercelli Alessandro , Pontecorvi Alfredo 
Published: October 2009

AbstractEven though several studies highlighted the role of maternal thyroid hormones (THs) during embryo–foetal development, direct evidence of their interaction with embryonic thyroid receptors (TRs) is still lacking. We generated a transgenic mouse model ubiquitously expressing a reporter gene tracing TH action during development. We engineered a construct (TRE2×) containing two TH‐responsive elements controlling the expression of the LacZ reporter gene, which encodes β‐galactosidase (β‐gal). The specificity of the TRE2× activation by TH was evaluated in NIH3T3 cells by cotransfecting TRE2× along with TRs, retinoic or oestrogen receptors in the presence of their specific ligands. TRE2× transgene was microinjected into the zygotes, implanted in pseudopregnant BDF1 (a first‐generation (F1) hybrid from a cross of C57BL/6 female and a DBA/2 male) mice and transgenic mouse models were developed. β‐gal expression was assayed in tissue sections of transgenic mouse embryos at different stages of development. In vitro, TRE2× transactivation was observed only following physiological T3 stimulation, mediated exclusively by TRs. In vivo, β‐gal staining, absent until embryonic day 9.5–10.5 (E9.5–E10.5), was observed as early as E11.5–E12.5 in different primordia (i.e. central nervous system, sense organs, intestine, etc.) of the TRE2× transgenic embryos, while the foetal thyroid function (FTF) was still inactive. Immunohistochemistry for TRs essentially colocalized with β‐gal staining. No β‐gal staining was detected in embryos of hypothyroid transgenic mice. Importantly, treatment with T3 in hypothyroid TRE2× transgenic mice rescued β‐gal expression. Our results provide in vivo direct evidence that during embryonic life and before the onset of FTF, maternal THs are transcriptionally active through the action of embryonic TRs. This model may have clinical relevance and may be employed to design end‐point assays for new molecules affecting THs action.
PKA‐Mediated Golgi Remodeling During cAMP Signal Transmission
Authors: Mavillard Fabiola , Hidalgo Josefina , Megias Diego , Levitsky Kostantin L. , Velasco Angel 
Published: October 2009

Abstract Cyclic AMP (cAMP)‐dependent protein kinase A (PKA) is part of the set of signaling proteins that are stably associated to the cytosolic surface of Golgi membranes in mammalian cells. In principle, Golgi‐associated PKA could participate in either signal transduction events and/or the coordination of Golgi transport activities. Here, we show data indicating that although Golgi‐associated PKA is activated fast and efficiently during cell stimulation by an extracellular ligand it does not contribute significantly to cAMP signal transmission to the nucleus. Instead, most of the PKA catalytic subunits Cαderived from the Golgi complex remain localized in the perinuclear cytoplasm where they induce changes in Golgi structural organization. Thus, in stimulated cells the Golgi complex appears collapsed, showing increased colocalization of previously segregated markers and exhibiting merging of different proximal cisternae within a single stack. In contrast, the trans‐Golgi network remains as a separate compartment. Consequently, the rate of protein transport is increased whereas glycan processing is not severely affected. This remodeling process requires the presence of PKA activity associated to the Golgi membranes. Together these data indicate that Golgi‐associated PKA activity is involved in the adaptation of Golgi dynamic organization to extracellular signaling events.
Three‐dimensional visualization of renal artery stenosis by 64‐channel multiple detector‐row computed tomographical angiography: review of two paediatric cases
Authors: Ueda N , Iwayama H , Funahashi Y , Suzuki K 
Published: October 2009

AbstractThree‐dimensional visualization of renal arteries has recently been established by helical contrast‐enhanced multiple detector‐row computed tomographical angiography (MDCTA) in adults. So far, no information is available on its use in children. We reported two children with renal artery stenosis detected by 64‐channel MDCTA. The first patient probably had fibromuscular dysplasia and the other neurofibromatosis type1. The technique showed a left renal artery stenosis with a small left kidney in the first patient and a right renal artery stenosis in the second.Conclusion:  MDCTA is an accurate and noninvasive imaging technique, easily performed in children, and can be used as an alternative diagnostic modality in children with suspected renovascular hypertension.