bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly frequent anti‐idiotype antibody in cynomolgus monkeys developed against mouse‐derived regions of anti‐Fas antibody humanized by complementarity determining region grafting
Authors: Saito‐Yabe M , Yoshigae Y , Takasaki W , Kurihara A , Ikeda T , Okazaki O
Published: July 2009

Background and purpose: We investigated the immunogenicity of a humanized anti‐human Fas monoclonal antibody, R‐125224, in cynomolgus monkeys to estimate its efficacy, as well as its toxicity in clinical situations.

Experimental approach: R‐125224 was intravenously administered to cynomolgus monkeys at single doses of 0.4, 1.2, 6 and 30 mg·kg−1, and the plasma concentrations of R‐125224 and anti‐R‐125224 antibody (ARA) were measured. We conducted a competitive enzyme‐linked immunosorbent assay to determine which part of R‐125224 was recognized by ARA. We also examined the retention of radioactivity in mononuclear cells and granulocytes after the injection of [125I]‐R‐125224 to a collagen‐induced arthritis monkey model.

Key results: After i.v. administration of R‐125224, the elimination of the plasma R‐125224 concentrations was accelerated at around 10 days post‐dose, and 10 of 12 monkeys were ARA positive. From an epitope analysis of ARA, the ARA produced in monkeys recognized the mouse‐derived regions located in complementarity determining regions, but could not recognize the human IgG. After the injection of [125I]‐R‐125224 to a collagen‐induced arthritis monkey model, a significantly longer retention of the radioactivity in mononuclear cells compared to granulocytes was observed.

Conclusions and implications: In monkeys, the development of antibodies against R‐125224 is rapid and highly frequent. Our hypothesis is that this highly frequent development of ARA might be due to the binding of R‐125224 to immune cells, and its circulation in monkey blood might contribute to an increase in its chances of being recognized as an immunogen.
Activities of Urease and Nickel Uptake of Helicobacter pylori Proteins are Media‐ and Host‐Dependent
Authors: Wolfram Lutz , Bauerfeind Peter
Published: July 2009

Background:  Nickel‐dependent urease activity and nickel supply are essential for successful colonization of Helicobacter pylori in the acidic environment of the human stomach. A comparison of media effects on these two activities have never been carried out. Additionally to H. pylori we cultivated an Escherichia coli strain expressing the urease and the nickel transporter NixA of H. pylori on the same four media and measured in all cases urease and nickel uptake activity.

Aim:  To compare nickel uptake and urease activity on an inter‐ and intraspecies level.

Results:  In H. pylori nickel uptake (four to 200 times) and urease activities (400 to 30,000 times) were found to be much higher in comparison to the tested E. coli strain after growth on all media. These differences could not be explained by reduced protein amounts in the heterologous host E. coli. On which media the two bacteria extracted most of the nickel were organism‐dependent: E. coli on Brucella Broth, H. pylori on Trypticase Soy Broth, and Minimal Media.

Conclusion:  H. pylori took nickel much more efficiently up than E. coli. The observed differences in urease activity are most likely due to additional protein components absent in the recombinant E. coli strain. The observed variety in nickel uptake and urease activities on the different media in the same organism depended on the intrinsic nickel content and chelating capacities of media components. Different culture conditions may lead to varying results; generalizations should be concluded only after excluding their media dependence.
Oxidative Stress in Helicobacter pylori Infection: Does Supplementation with Vitamins C and E Increase the Eradication Rate?
Authors: Sezikli Mesut , Çetinkaya Züleyha Akkan , Sezikli Hayrünnisa , Güzelbulut Fatih , Tiftikçi Arzu , Tüzün İnce Ali , Gökden Yasemin , Yaşar Bülent , Atalay Sacide , Övünç Kurdaş Oya
Published: July 2009

Aim:  This study aims to assess the antioxidant property of vitamins E and C in Helicobacter pylori infection, and to determine if adding them to standard triple therapy plus bismuth subcitrate increases the H. pylori eradication rate.

Methods:  This study included 160 patients infected with H. pylori, who were randomized into one of two groups. Patients in group A (n = 80) received lansoprazole (30 mg, b.i.d.), amoxicillin (1000 mg, b.i.d.), clarithromycin (500 mg, b.i.d.), and bismuth subcitrate (300 mg, q.i.d.) for 14 days, while patients in group B (n = 80) received vitamin C (500 mg, b.i.d.) and vitamin E (200 IU, b.i.d.) for 30 days, in addition to lansoprazole (30 mg, b.i.d.), amoxicillin (1000 mg, b.i.d.), clarithromycin (500 mg, b.i.d.), and bismuth subcitrate (300 mg, q.i.d.) for 14 days. Total antioxidant capacity (TAC) was evaluated with a Randox kit. Success rate was calculated using both intention‐to‐treat (ITT) and per‐protocol (PP) analyses.

Results:  One hundred and sixty patients were analyzed using ITT analysis. One hundred and fifty‐three patients completed the study. In group A, H. pylori eradication was achieved in 48 (60%) of the 80 patients included in the ITT analysis, and in 48 (64%) of the 75 patients included in the PP analysis. In group B, H. pylori eradication was achieved in 73 (91.25%) of the 80 included in the ITT analysis and in 73 (93.5%) of the 78 patients included in the PP analysis. The eradication rate was significantly higher in group B than in group A (p < .005). TAC was at the lower limit of normal in both groups and the difference between them was not statistically significant (p > .05).

Conclusion:  In group B, H. pylori eradication rate was 91.25%, which is higher than the ideal 80% eradication rate. The results of the present study show that adding the prescribed doses of vitamins E and C to antimicrobial therapy is effective in eradicating H. pylori infection.
An Assay for Evoked Locomotor Behavior inDrosophilaReveals a Role for Integrins in Ethanol Sensitivity and Rapid Ethanol Tolerance
Authors: Bhandari Poonam , Kendler Kenneth S. , Bettinger Jill C. , Davies Andrew G. , Grotewiel Mike
Published: July 2009

Background: Ethanol induces similar behavioral responses in mammals and the fruit fly,Drosophila melanogaster. By coupling assays for ethanol‐related behavior to the genetic tools available in flies, a number of genes have been identified that influence physiological responses to ethanol. To enhance the utility of theDrosophilamodel for investigating genes involved in ethanol‐related behavior, we explored the value of an assay that measures the sedative effects of ethanol on negative geotaxis, an evoked locomotor response.

Methods: We established eRING (ethanolRapidIterativeNegativeGeotaxis) as an assay for quantitating the sedative effects of ethanol on negative geotaxis (i.e., startle‐induced climbing). We validated the assay by assessing acute sensitivity to ethanol and rapid ethanol tolerance in several different control strains and in flies with mutations known to disrupt these behaviors. We also used eRING in a candidate screen to identify mutants with altered ethanol‐related behaviors.

Results: Negative geotaxis measured in eRING assays was dose‐dependently impaired by ethanol exposure. Flies developed tolerance to the intoxicating effects of ethanol when tested during a second exposure. Ethanol sensitivity and rapid ethanol tolerance varied across 4 control strains, but internal ethanol concentrations were indistinguishable in the 4 strains during a first and second challenge with ethanol. Ethanol sensitivity and rapid ethanol tolerance, respectively, were altered in flies with mutations inamnesiacandhangover, genes known to influence these traits. Additionally, mutations in the β integrin genemyospheroidand the α integrin genescabincreased the initial sensitivity to ethanol and enhanced the development of rapid ethanol tolerance without altering internal ethanol concentrations.

Conclusions: The eRING assay is suitable for investigating genetic mechanisms that influence ethanol sensitivity and rapid ethanol tolerance. Ethanol sensitivity and rapid ethanol tolerance depend on the function of α and β integrins in flies.
Parietal Gray Matter Volume Loss Is Related to Spatial Processing Deficits in Long‐Term Abstinent Alcoholic Men
Authors: Fein George , Shimotsu Ryan , Chu Russell , Barakos Jerome
Published: July 2009

Background:  We previously demonstrated relatively intact cognitive function (with the exception of suggestive evidence for persistent deficits in spatial information processing) in middle‐aged long‐term abstinent alcoholics (LTAA, abstinent for 6 months or more) compared to age and gender comparable nonalcoholic controls (NAC) (Fein et al., 2006).

Methods:  In the current study, we examine cortical gray matter volumes in the same samples to determine whether gray matter volumes in LTAA are consistent with the cognitive results – i.e., exhibiting gray matter volumes comparable to NAC in most brain regions, except for possible indications of persistent shrinkage in the parietal lobe subserving spatial information processing.

Results:  We found gray matter shrinkage in LTAA in the parietal lobe consistent with the spatial processing deficits in this same sample. More compelling, in LTAA, the magnitude of parietal gray matter shrinkage was negatively associated with spatial processing domain performance and positively associated with alcohol dose. Gray matter volume deficits were present in the occipital and other cortical tissue, but poorer visuospatial test performance correlated significantly with smaller volumes in the parietal cortex only.

Conclusions:  Taken together, the cognitive and structural imaging data provide compelling evidence that chronic alcohol abuse results in shrinkage of the parietal cortex with associated deficits in spatial information processing.
Microstructural Corpus Callosum Anomalies in Children With Prenatal Alcohol Exposure: An Extension of Previous Diffusion Tensor Imaging Findings
Authors: Wozniak Jeffrey R. , Muetzel Ryan L. , Mueller Bryon A. , McGee Christie L. , Freerks Melesa A. , Ward Erin E. , Nelson Miranda L. , Chang Pi‐Nian , Lim Kelvin O.
Published: July 2009

Background:  Several studies have now shown corpus callosum abnormalities using diffusion tensor imaging (DTI) in children with fetal alcohol spectrum disorders (FASD) in comparison with nonexposed controls. The data suggest that posterior regions of the callosum may be disproportionately affected. The current study builds on previous efforts, including our own work, and moves beyond midline corpus callosum to probe major inter‐hemispheric white matter pathways with an improved DTI tractographic method. This study also expands on our prior work by evaluating a larger sample and by incorporating children with a broader range of clinical effects including full‐criteria fetal alcohol syndrome (FAS).

Methods:  Participants included 33 children with FASD (8 FAS, 23 partial FAS, 2 static encephalopathy) and 19 nonexposed controls between the ages of 10 and 17 years. Participants underwent DTI scans and intelligence testing. Groups (FASD vs. controls) were compared on fractional anisotropy (FA) and mean diffusivity (MD) in 6 white matter tracts projected through the corpus callosum. Exploratory analyses were also conducted examining the relationships between DTI measures in the corpus callosum and measures of intellectual functioning and facial dysmorphology.

Results:  In comparison with the control group, the FASD group had significantly lower FA in 3 posterior tracts of the corpus callosum: the posterior mid‐body, the isthmus, and the splenium. A trend‐level finding also suggested lower FA in the genu. Measures of white matter integrity and cognition were correlated and suggest some regional specificity, in that only posterior regions of the corpus callosum were associated with visual‐perceptual skills. Correlations between measures of facial dysmorphology and posterior regions of the corpus callosum were nonsignificant.

Conclusions:  Consistent with previous DTI studies, these results suggest that microstructural posterior corpus callosum abnormalities are present in children with prenatal alcohol exposure and cognitive impairment. These abnormalities are clinically relevant because they are associated with cognitive deficits and appear to provide evidence of abnormalities associated with prenatal alcohol exposure independent of dysmorphic features. As such, they may yield important diagnostic and prognostic information not provided by the traditional facial characteristics.
Intestinal Dysbiosis: A Possible Mechanism of Alcohol‐Induced Endotoxemia and Alcoholic Steatohepatitis in Rats
Authors: Mutlu Ece , Keshavarzian Ali , Engen Phillip , Forsyth Christopher B. , Sikaroodi Masoumeh , Gillevet Patrick
Published: July 2009

Background: Clinical and animal data indicate that gut‐derived endotoxin and other luminal bacterial products are necessary cofactors for development of alcoholic liver disease (ALD). Although gut leakiness is clearly an important cause of endotoxemia in ALD, it cannot fully explain endotoxemia in all ALD subjects and thus other factors may be involved. One possible factor is a change in gut microbiota composition (dysbiosis). Thus, the aim of our study was to interrogate the gut bacterial microbiota in alcohol‐fed rats to see if chronic alcohol consumption affects gut bacteria composition.

Method: Male Sprague–Dawley rats were given either alcohol or dextrose intragastrically by gavage twice daily for up to 10 weeks. A subgroup of rats was also given either a probiotic (lactobacillus GG) or a prebiotic (oats) by gavage. Ileal and colonic mucosal‐attached microbiota composition were interrogated by Length Heterogeneity PCR (LH‐PCR) fingerprinting.

Results: Bacterial microbiota composition in alcohol‐fed rats is not different from dextrose‐fed rats at weeks 4 and 6. Mucosa‐associated microbiota composition in the colon is altered at 10 weeks of daily alcohol gavage. Both LGG and oats prevented alcohol‐induced dysbiosis up to 10 weeks of alcohol treatment.

Conclusion: Daily alcohol consumption for 10 weeks alters colonic mucosa‐associated bacterial microbiota composition in rats. Our data showed, for the first time, that daily alcohol consumption can affect colonic microbiome composition and suggest that dysbiosis may be an important mechanism of alcohol‐induced endotoxemia. Further studies are needed to determine how dysbiotic microbiota contributes to development of ALD and whether therapeutic interventions targeted towards dysbiotic microbiota can prevent complications of alcoholism like ALD.
Social Interactions and Entrepreneurial Activity
Authors: Giannetti Mariassunta , Simonov Andrei
Published: July 2009

We show that individuals residing in highly entrepreneurial neighborhoods are more likely to become entrepreneurs and invest more into their own businesses, even though their entrepreneurial profits are lower and their alternative job opportunities more attractive. Our results suggest that peer effects create nonpecuniary benefits from entrepreneurial activity and play an important role in the decision to become an entrepreneur. Alternative explanations, such as entry costs, social learning, and informal credit markets, are not supported by the data.
Patents, Thickets and the Financing of Early‐Stage Firms: Evidence from the Software Industry
Authors: Cockburn Iain M. , MacGarvie Megan J.
Published: July 2009

Legal changes in the patentability of software since the mid 1990s have resulted in a substantial increase in the number of patents on software inventions. We focus here on the impact of transactions costs associated with patent “thickets” on new entrants' interactions with the capital markets. Using data on the financing of entrants into 27 narrowly defined software markets, we show that start‐up software companies operating in markets characterized by denser patent thickets saw their initial acquisition of VC funding delayed relative to firms in markets less affected by patents after the mid 1990s. The relationship between patent thickets and subsequent financing activity such as IPO or acquisition is more complex, but there is weak evidence that firms without patents became less likely to go public if they operated in a market characterized by patent thickets. Firms with patents are more likely to be funded or experience a liquidity event. However, the application for a patent appears to matter more than its grant.
Entrepreneurial Financing, Advice, and Agency Costs
Authors: Strausz Roland
Published: July 2009

We develop a model to study the interplay between advice and agency costs in entrepreneurial financing. We demonstrate a tension between the entrepreneur's motivation for effort and the investor's willingness to finance the project. Advice to the entrepreneur exacerbates this tension. Consequently, optimal financing contracts may involve full, partial, or no advice. With partial advice, information flows need to be controlled carefully. Such control is better when advice and finance are integrated as observed by venture capitalists.
Accidents and Unpleasant Incidents: Worry in Transport and Prediction of Travel Behavior
Authors: Backer‐Grøndahl Agathe , Fyhri Aslak , Ulleberg Pål , Amundsen Astrid Helene
Published: July 2009

Worry on nine different means of transport was measured in a Norwegian sample of 853 respondents. The main aim of the study was to investigate differences in worry about accidents and worry about unpleasant incidents, and how these two sorts of worry relate to various means of transport as well as transport behavior. Factor analyses of worry about accidents suggested a division between rail transport, road transport, and nonmotorized transport, whereas analyses of worry about unpleasant incidents suggested a division between transport modes where you interact with other people and “private” transport modes. Moreover, mean ratings of worry showed that respondents worried more about accidents than unpleasant incidents on private transport modes, and more about unpleasant incidents than accidents on public transport modes. Support for the distinction between worry about accidents and unpleasant incidents was also found when investigating relationships between both types of worry and behavioral adaptations: worry about accidents was more important than worry about unpleasant incidents in relation to behavioral adaptations on private means of transport, whereas the opposite was true for public means of transport. Finally, predictors of worry were investigated. The models of worry about accidents and worry about unpleasant incidents differed as to what predictors turned out significant. Knowledge about peoples' worries on different means of transport is important with regard to understanding and influencing transport and travel behavior, as well as attending to commuters' welfare.
Science versus Human Welfare? Understanding Attitudes toward Animal Use
Authors: Knight Sarah , Vrij Aldert , Bard Kim , Brandon Doug
Published: July 2009

Scientists have been portrayed as having an uncaring attitude toward the use of animals and being inclined to reject the possibility of animal mind (Baldwin, 1993; Blumberg & Wasserman, 1995), yet there is little empirical research to support these claims. We examined why disparate attitudes toward animal use are held. Scientists, animal welfarists, and laypersons (N = 372) were compared on questionnaire responses that measured attitudes toward four types of animal use, and factors that might underlie these views (including belief in animal mind). As expected, scientists and animal welfarists held polarized views on all measures, whereas laypersons fell between the two. Animal welfarists were consistently opposed to all types of animal use, whereas scientists expressed support for the use of animals for medical research, but not for dissection, personal decoration, and entertainment. Animal welfarists showed high levels of belief in animal mind for 13 animal types, and scientists believed some of the 13 animals to have at least a moderate capacity for cognition and most to have at least a moderate capacity for sentience. Hence, the negative image of the science community that is often portrayed was not supported by our data. Findings were discussed in relation to external (group membership) and internal (belief systems) factors, and it is concluded that some people hold fixed attitudes toward animal use, whereas others are more influenced by context.
Animal Abuse as a Sentinel for Human Violence: A Critique
Authors: Patterson‐Kane Emily G. , Piper Heather
Published: July 2009

It has been suggested that acts of violence against human and nonhuman animals share commonalities, and that animal abuse is a sentinel for current or future violence toward people. The popular and professional acceptance of strong connections between types of violence is beginning to be used to justify social work interventions and to influence legal decision making, and so requires greater scrutiny. Examination of the limited pool of empirical data suggests that animal abuse is relatively common among men, with violent offenders having an increased probability of reporting prior animal abuse—with the majority of violent offenders not reporting any animal abuse. Causal explanations for “the link,” such as empathy impairment or conduct disorder, suffer from a lack of validating research and, based on research into interhuman violence, the assumption that violence has a predominant, single underlying cause must be questioned. An (over)emphasis on the danger that animal abusers pose to humans serves to assist in achieving a consensus that animal abuse is a serious issue, but potentially at the cost of failing to focus on the most common types of abuse, and the most effective strategies for reducing its occurrence. Nothing in this review and discussion should be taken as minimizing the importance of animals as frequent victims of violence, or the co‐occurrence of abuse types in “at‐risk” households. However, given the weakness of the underlying data, emphasizing the indiscriminate dangerousness of all animal abusers may have unforeseen and unwanted consequences.
Forecasting Pollen Concentration by a Two‐Step Functional Model
Authors: Valderrama Mariano J. , Ocaña Francisco A. , Aguilera Ana M. , Ocaña‐Peinado Francisco M.
Published: July 2009

Summary A functional regression model to forecast the cypress pollen concentration during a given time interval, considering the air temperature in a previous interval as the input, is derived by means of a two‐step procedure. This estimation is carried out by functional principal component (FPC) analysis and the residual noise is also modeled by FPC regression, taking as the explicative process the pollen concentration during the earlier interval. The prediction performance is then tested on pollen data series recorded in Granada (Spain) over a period of 10 years.
A Bayesian Chi‐Squared Goodness‐of‐Fit Test for Censored Data Models
Authors: Cao Jing , Moosman Ann , Johnson Valen E.
Published: July 2009

SummaryWe propose a Bayesian chi‐squared model diagnostic for analysis of data subject to censoring. The test statistic has the form of Pearson's chi‐squared test statistic and is easy to calculate from standard output of Markov chain Monte Carlo algorithms. The key innovation of this diagnostic is that it is based only on observed failure times. Because it does not rely on the imputation of failure times for observations that have been censored, we show that under heavy censoring it can have higher power for detecting model departures than a comparable test based on the complete data. In a simulation study, we show that tests based on this diagnostic exhibit comparable power and better nominal Type I error rates than a commonly used alternative test proposed byAkritas(1988, Journal of the American Statistical Association 83,222–230). An important advantage of the proposed diagnostic is that it can be applied to a broad class of censored data models, including generalized linear models and other models with nonidentically distributed and nonadditive error structures. We illustrate the proposed model diagnostic for testing the adequacy of two parametric survival models for Space Shuttle main engine failures.
Risk‐Group‐Specific Dose Finding Based on an Average Toxicity Score
Authors: Bekele B. Nebiyou , Li Yisheng , Ji Yuan
Published: July 2009

Summary We propose a Bayesian dose‐finding design that accounts for two important factors, the severity of toxicity and heterogeneity in patients' susceptibility to toxicity. We consider toxicity outcomes with various levels of severity and define appropriate scores for these severity levels. We then use a multinomial‐likelihood function and a Dirichlet prior to model the probabilities of these toxicity scores at each dose, and characterize the overall toxicity using an average toxicity score (ATS) parameter. To address the issue of heterogeneity in patients' susceptibility to toxicity, we categorize patients into different risk groups based on their susceptibility. A Bayesian isotonic transformation is applied to induce an order‐restricted posterior inference on the ATS. We demonstrate the performance of the proposed dose‐finding design using simulations based on a clinical trial in multiple myeloma.
Microbiological profile of untreated subjects with localized aggressive periodontitis
Authors: Faveri Marcelo , Figueiredo Luciene Cristina , Duarte Poliana Mendes , Mestnik Maria Josefa , Mayer Marcia Pinto Alves , Feres Magda
Published: July 2009

Aim: The microbial profile of localized aggressive periodontitis (LAgP) has not yet been determined. Therefore, the aim of this study was to evaluate the subgingival microbial composition of LAgP.

Material and Methods: One hundred and twenty subjects with LAgP (n=15), generalized aggressive periodontitis (GAgP, n=25), chronic periodontitis (ChP, n=30) or periodontal health (PH, n=50) underwent clinical and microbiological assessment. Nine subgingival plaque samples were collected from each subject and analysed for their content of 38 bacterial species using checkerboard DNA–DNA hybridization.

Results: Red complex and some orange complex species are the most numerous and prevalent periodontal pathogens in LAgP. The proportions of Aggregatibacter actinomycetemcomitans were elevated in shallow and intermediate pockets of LAgP subjects in comparison with those with GAgP or ChP, but not in deep sites. This species also showed a negative correlation with age and with the proportions of red complex pathogens. The host‐compatible Actinomyces species were reduced in LAgP.

Conclusion: A. actinomycetemcomitans seems to be associated with the onset of LAgP, and Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Campylobacter gracilis, Eubacterium nodatum and Prevotella intermedia play an important role in disease progression. Successful treatment of LAgP would involve a reduction in these pathogens and an increase in the Actinomyces species.
Acquired bullous dermatosis associated with IgA multiple myeloma: a case report
Authors: Barnadas Maria A. , Gelpí Carmen , Martínez Laura , Curell Román , Martino Rodrigo , Alomar Agustín
Published: July 2009

We present the case of a patient with IgA paraprotein who developed hemorrhagic subepidermal vesicles and bullae with numerous neutrophils. Direct immunofluorescence test (DIF) showed weak deposits of IgA lambda paraprotein at the dermal–epidermal junction and at the intercellular level in the basal layer of the epidermis, and stronger deposits in a perivascular and diffuse pattern in the dermis. Indirect immunofluorescence (IIF) test revealed the presence of circulating IgA lambda antibodies reacting with the intercellular space of monkey and guinea pig esophagus and human skin. A blood test revealed an IgA lambda paraprotein and multiple myeloma stage I(0) was diagnosed in a later hematological study. Dapsone was prescribed and cutaneous lesions improved. This is the second report of subepidermal vesicles and bullae with dermal deposits of IgA paraprotein appearing prior to diagnosis of an IgA multiple myeloma, and it is a unique case with circulating IgA lambda antibodies reacting with the intercellular space of epithelia.

Barnadas MA, Gelpí C, Martínez L, Curell R, Martino R, Alomar A. Acquired bullous dermatosis associated with IgA multiple myeloma: a case report.
Scleromyxedema with an interstitial granulomatous‐like pattern: a rare histologic variant mimicking granuloma annulare
Authors: Rongioletti Franco , Cozzani Emanuele , Parodi Aurora
Published: July 2009

Scleromyxedema is the generalized and sclerodermoid form of lichen myxedematosus. Its typical histological features include a diffuse deposition of mucin in the papillary and mid reticular dermis, an increased of collagen deposition, and a proliferation of irregularly arranged fibroblasts. We describe a 76‐year‐old man presenting with scleromyxedema associated with IgGλ monoclonal gammopathy whose biopsy showed histological features of an interstitial granulomatous‐like process consistent with interstitial granuloma annulare. The significance of these unusual granulomatous findings in the setting of scleromyxedema are unknown and have been described only once in the literature. This observation expands the spectrum of scleromyxedema and highlights the difficulty in diagnosing this disabling condition.

Rongioletti F, Cozzani E, Parodi A. Scleromyxedema with an interstitial granulomatous‐like pattern: a rare histologic variant mimicking granuloma annulare.
T‐lymphocyte‐induced, fas‐mediated apoptosis is associated with early keratinocyte differentiation
Authors: Daehn Ilse S. , Varelias Antiopi , Rayner Timothy E.
Published: July 2009

Please cite this paper as: T‐lymphocyte‐induced, fas‐mediated apoptosis is associated with early keratinocyte differentiation. Experimental Dermatology 2009.

Abstract:  The development of eczematous lesions is thought to be due in part to a breakdown in skin barrier function as a result of T lymphocytes (T cells) invading the skin causing epidermal keratinocyte apoptosis. In this study, we investigated the interaction of T cells and keratinocytes on apoptosis and terminal differentiation using an in vitro co‐culture system. Experiments were performed using the HaCaT keratinocyte cell line or normal human epidermal keratinocytes. Activated human peripheral blood‐derived T cells were found to induce Fas‐dependent keratinocyte apoptosis by up to sixfold. Increased Fas was associated with increased IFN‐γ. The T‐cell apoptotic signal was found to target preferentially keratinocytes in the very early stages of terminal differentiation, such as those with low levels of α6‐integrin expression, and result in subsequent increased caspase 3 activity. This observation was accompanied by a marked increase in keratinocyte ICAM‐1 expression and its ligand LFA‐1 on T cells. Our data suggest that T cells may initiate the onset of keratinocyte terminal differentiation making them more susceptible to Fas‐dependent cell death signals delivered by the T cells.
Injury downregulates the expression of the human cathelicidin protein hCAP18/LL‐37 in atopic dermatitis
Authors: Mallbris Lotus , Carlén Lina , Wei Tianling , Heilborn Johan , Nilsson Margareta Frohm , Granath Fredrik , Ståhle Mona
Published: July 2009

Please cite this paper as: Injury downregulates the expression of the human cathelicidin protein hCAP18/LL‐37 in atopic dermatitis. Experimental Dermatology 2009; 19: 442–449.

Abstract:  Reduced production of antimicrobial peptides was proposed to contribute to susceptibility for skin infections in atopic dermatitis (AD). Focusing on the human cathelicidin protein, hCAP18, the aim of the present study was to explore whether reduced hCAP18 expression is a constitutive trait in AD and if established inducers affect the expression of hCAP18 in the skin of AD. First, we compared levels of hCAP18 mRNA between lesional skin in AD and psoriasis and verified significantly lower expression of hCAP18 mRNA in AD. In non‐lesional skin, however, there was no difference between AD, psoriasis and healthy, indicating that there is no constitutive defect in the production of hCAP18 in AD patients. In healthy skin, hCAP18 was reported to be rapidly induced following wounding and here we verified this pattern in healthy controls and in psoriasis. In AD lesions, however, the expression of hCAP18 mRNA was markedly suppressed following wounding. Obviously, the inflammation in AD lesions neutralizes the expected induction of hCAP18 and even induces suppression. Notably, the mechanism to upregulate hCAP18 following vitamin D treatment was functional in lesional as well as in non‐lesional AD indicating that the CAMP gene is normally regulated in this respect. In addition, cultured primary keratinocytes from non‐lesional skin of psoriasis, AD and healthy skin, upregulated hCAP18mRNA following treatment with vitamin D. Itching is a hallmark of AD and scratching inevitably injures the skin. Failure to upregulate hCAP18 in eczema following injury is likely to affect antimicrobial protection and tissue repair in AD.
Why do melanomas get so dark?
Authors: Lazova Rossitza , Pawelek John M.
Published: July 2009

Abstract:  Cutaneous malignant melanomas often exhibit pigmented regions that are darker than the surrounding skin. While melanoma cells are the original source of the melanin, keratinocytes and melanophages also contribute to the tumor colour because they contain melanin obtained from melanoma cells. However, little is known of the origin of darkly pigmented melanoma cells or of the molecular pathways regulating their melanin production. Here we discuss observations that dark melanoma cells emerge from within populations of melanoma in situ and that, in addition to producing abundant dark pigment, they appear to be undergoing autophagy. Moreover, autophagy appears to be a common trait of invasive melanoma cells in the dermis. The underlying cause of this phenomenon may stem from aberrant production of glycosylation structures known as β1,6‐branched oligosaccharides. Our studies of dark cutaneous melanomas were prompted by analyses of experimental mouse macrophage‐melanoma hybrids fused in the laboratory. Like melanoma cells in cutaneous malignant melanoma, experimental hybrids also displayed abundant dark pigment and autophagy, and had high levels of β1,6‐branched oligosaccharides. Whether or not darkly pigmented malignant melanoma cells originate from fusion with macrophages in vivo remains to be determined. In any event, pigmentation in melanoma, long considered as a secondary aspect of the malignancy, may be a visible warning that the cells have gained competence for invasion and metastasis.
Myeloablative irradiation in non‐human primates
Authors: Watts K.L. , Beard B.C. , Wood B.L. , Kiem H.P.
Published: July 2009

Purpose  We used total body irradiation (TBI) as conditioning for cord blood transplantation studies in pigtailed macaques. In these studies, different doses of TBI were explored to obtain optimal myelosuppression with acceptable radiation‐related side effects.

Methods  Four macaques received TBI ranging from 800 to 1320 cGy, followed by standard post‐transplant care. Hematopoietic recovery was monitored by CBC and donor contribution by variable number of tandem repeats analysis.

Results  Animals receiving 800 or 1020 cGy TBI tolerated the irradiation well with autologous recovery of neutrophils within 24 days. At a dose of 1200 cGy, neither autologous recovery nor extramedullary toxicity was observed. A fourth animal received 1320 cGy of TBI and suffered significant toxicity necessitating termination of the study.

Conclusions  We conclude that previously considered myeloablative doses of TBI allowed for autologous recovery in the pigtailed macaque, and that a dose of 1200 cGy may be most appropriate, providing both myeloablation and acceptable non‐hematopoietic toxicities.
Unprecedented pathogen‐inducible complex oxylipins from flax – linolipins A and B
Authors: Chechetkin Ivan R. , Mukhitova Fakhima K. , Blufard Alexander S. , Yarin Andrey Y. , Antsygina Larisa L. , Grechkin Alexander N.
Published: July 2009

Oxylipins constitute a large family of bioregulators, biosynthesized via unsaturated fatty acid oxidation. This study reports the detection of an unprecedented family of complex oxylipins from flax leaves. Two major members of this family, compounds 1 and 2, were isolated and purified. Their structures were evaluated using NMR and MS analyses. Both compounds were identified as monogalactosyldiacylglycerol species. Compound 1 contains one α‐linolenoyl residue and one residue of (9Z,11E,1′Z,3′Z)‐12‐(1′,3′‐hexadienyloxy)‐9,11‐dodecadienoic, (ω5Z)‐etherolenic acid at positions sn‐1 and sn‐2, respectively. Compound 2 possesses (ω5Z)‐etherolenic acid residues at both position sn‐1 and position sn‐2. We suggest the trivial names linolipin A and linolipin B for compounds 1 and 2, respectively, and the collective name linolipins for this new family of complex oxylipins. The linolipin content of flax leaves increased significantly in response to pathogenesis. Thus, accumulation of esterified antimicrobial divinyl ethers may be of relevance to plant defense.
High‐level production and characterization of a G‐protein coupled receptor signaling complex
Authors: Marino Stephen F.
Published: July 2009

Elucidation of the molecular details of signal transduction through G‐protein coupled receptors (GPCRs) awaits the solution of high‐resolution structures of the receptor species involved in passing the extracellular information across the plasma membrane. The critical challenge in this effort is the production of sufficient quantities of active and homogeneous receptor species amenable to crystallization screening. We describe here the high‐level expression in mammalian cells and characterization of a fusion complex between the kappa opioid receptor and its cognate G‐protein alpha subunit, Gαi1. Optimization of growth conditions resulted in the highest level of active binding sites reported to date for either opioid receptors or GPCR–Gα fusions. In cells, the kappa opioid receptor was stabilized against proteolysis in the context of the fusion protein and was competent to bind both agonists and antagonists. Coupling of the kappa opioid receptor with the Gα subunit was demonstrated by changes in agonist affinity in the presence of guanine nucleotides and by agonist‐induced increases in the rate of guanine nucleotide hydrolysis. In addition to representing a physiologically relevant signaling complex, the additional hydrophilic surface area provided by the G‐protein may enhance the chances of producing well‐diffracting crystals from the purified complex.
Advanced glycation end products and lipopolysaccharide synergistically stimulate proinflammatory cytokine/chemokine production in endothelial cells via activation of both mitogen‐activated protein kinases and nuclear factor‐κB
Authors: Liu Jinghua , Zhao Shanchao , Tang Jing , Li Zhijie , Zhong Tianyu , Liu Yawei , Chen Dengyu , Zhao Mingzhe , Li Yusheng , Gong Xiaowei , Deng Peng , Wang Jiang H. , Jiang Yong
Published: July 2009

It has been well documented that both endogenous inflammatory mediator advanced glycation end products (AGEs) and exogenous inflammatory inducer lipopolysaccharide play key roles in the initiation and development of inflammatory diseases. However, the combined inflammation‐stimulatory effect of AGEs and lipopolysaccharide on endothelial cells, and, furthermore, the underlying signal transduction pathways involved, have not been fully elucidated. We found that in vitro co‐stimulation with AGE‐human serum albumin (HSA) and lipopolysaccharide exhibits a synergistic effect on proinflammatory cytokine/chemokine interleukin‐6, interleukin‐8 and monochemoattractant protein‐1 production in human umbilical vein endothelial cells. Similar to lipopolysaccharide, AGE‐HSA stimulation induced mitogen‐activated protein kinase phosphorylation and nuclear factor‐κB nuclear translocation in human umbilical vein endothelial cells, which was further enhanced by a combination of the two stimulants. Pharmacological inhibitions of each individual signaling pathway, including p38, extracellular signal‐regulated kinase 1/2, Jun N‐terminal kinase and nuclear factor‐κB, revealed that activation of all of these four pathways is necessary for the effective induction of interleukin‐6, interleukin‐8 and monochemoattractant protein‐1 by both AGE‐HSA and lipopolysaccharide. These results suggest that AGEs and lipopolysaccharide cooperatively induce proinflammatory cytokine/chemokine production by activating mitogen‐activated protein kinases and nuclear factor‐κB in endothelial cells, thus amplifying the inflammatory response and resulting in tissue damage.
Impaired contractile function and mitochondrial respiratory capacity in response to oxygen deprivation in a rat model of pre‐diabetes
Authors: Essop M. F. , Anna Chan W. Y. , Valle A. , García‐Palmer F. J. , Du Toit E. F.
Published: July 2009

Aim:  Obesity is a major contributor to the global burden of disease and is closely associated with the development of type 2 diabetes and cardiovascular diseases. This study tested the hypothesis that mitochondrial respiratory capacity of the pre‐diabetic heart is decreased leading to impaired contractile function and tolerance to ischaemia/reperfusion.

Methods:  Eight‐week‐old male Wistar rats were fed a high caloric diet for 16 weeks after which anthropometric, metabolic, cardiac and mitochondrial parameters were evaluated vs. age‐matched lean controls. Cardiac function (working heart perfusions) and mitochondrial respiratory capacity were assessed at baseline and in response to acute oxygen deprivation.

Results:  Rats fed the high caloric diet exhibited increased body weight and visceral fat vs. the control group. Heart weights of obese rats were also increased. Triglyceride, fasting plasma insulin and free fatty acid levels were elevated, while high‐density lipoprotein cholesterol levels were reduced in the obese group. Contractile function was attenuated at baseline and further decreased after subjecting hearts to ischaemia‐reperfusion. Myocardial infarct sizes were increased while ADP phosphorylation rates were diminished in obese rats. However, no differences were found for mtDNA levels and the degree of oxidative stress‐induced damage.

Conclusions:  These data show that decreased mitochondrial bioenergetic capacity in pre‐diabetic rat hearts may impair respiratory capacity and reduce basal contractile function and tolerance to acute oxygen deprivation.
Consensus statement on management in the UK: Transoral laser assisted microsurgical resection of early glottic cancer
Authors: Bradley P.J. , Mackenzie K. , Wight R. , Pracy P. , Paleri V. ,   On behalf of ENT‐UK Head & Neck Group
Published: July 2009

Background:  Transoral laser assisted microsurgical resection of early glottic laryngeal cancer is a relatively new treatment modality that is practised in many centres across the UK. In the absence of the results from randomised clinical trials, clinicians may be guided by an expert panel consensus statement on transoral laser assisted microsurgical resection of early squamous cell cancer of the larynx.

Objective:  To provide consensus recommendations on the various aspects of transoral laser assisted microsurgical resection for early glottic cancer.

Evaluation method:  Nine centres across the UK were invited to describe current practice and outcomes for transoral laser assisted microsurgical resection of early glottic cancer. Four working groups were created to draw consensus on standard of care, surgical procedures, outcomes measures and training/certification. The feedback from these groups was integrated into the consensus statement.

Conclusions:  The consensus meeting confirmed the stablished and widespread use of transoral laser assisted microsurgical resection for early glottic cancer throughout the UK. The common experience gained allowed a full discussion of all aspects of the management with consensus achieved in key areas of standards of care, surgery, histopathologic reporting, outcomes assessment and training. This consensus statement will result in closer auditing of management and dissemination of results.
A retrospective cohort study of nasopharyngeal adenocarcinoma: a rare histological type of nasopharyngeal cancer
Authors: Guo Z.M. , Liu W.W. , He J.H.
Published: July 2009

Objectives:  The purpose of this study was to investigate the clinical manifestations, Epstein‐Barr virus (EBV) serology, and treatment outcome of patients with nasopharyngeal adenocarcinoma (NPAC).

Design:  A retrospective study of clinical data from consecutive patients with NPAC identified between 1964 and 2000.

Setting:  A tertiary cancer center in China.

Participants:  Forty‐eight patients diagnosed with NPAC.

Main outcome measures:  Crosstabs and chi‐square test were conducted to study the association of positive VCA‐IgA levels among different pathological types of NPAC, and also to compare the proportions of local control rates in patients treated with different modalities. The survival rate was calculated using the Kaplan–Meier method, and the Log Rank test was used to compare the survival rates considering different factors. To balance the distribution bias, a multivariate COX model survival analysis was also performed.

Results:  Of the 48 NPAC patients identified, 45% presented with cervical metastasis. Pathologically, 58% of NPAC cases were common type and 42% were salivary gland type. The positive rate for the EBV antibody VCA‐IgA in all patients was 53% and only 24% in the salivary gland type of NPAC. The overall local control rate and the 5‐year disease‐free survival rates were 87% and 65% respectively. Patients treated with surgery plus radiotherapy (RT) had a significantly higher 5‐year disease‐free survival rate than patients receiving RT alone (89%versus 75% respectively) (P = 0.039). Multivariate analysis confirmed that treatment modality was the significant factor influencing patient survival (P = 0.027) and the pathological type was not a factor predicting survival.

Conclusions:  Nasopharyngeal adenocarcinoma is a distinct entity in all types of nasopharyngeal carcinoma and EBV serology has limited value in its diagnosis. The combination of surgery and RT should be considered for treatment of early lesions of NPAC.
Preoperative blood sugar and C‐reactive protein associated with persistent discharge after incision and drainage for patients with deep neck abscesses
Authors: Liu S.‐A. , Liang M.‐T. , Wang C.‐P. , Wang C.‐C. , Lin W.‐D. , Ho H.‐C. , Chiu Y.‐T.
Published: July 2009

Objectives:  The aim of this study was to investigate whether preoperative C‐reactive protein (CRP) and blood sugar correlated with persistent discharge after incision and drainage for patients with deep neck abscesses.

Study design:  Retrospective data analysis.

Setting:  Tertiary referral centre.

Participants:  A total of 204 patients who underwent operation for deep neck abscess.

Main outcome measures:  Persistent discharge after operation.

Results:  One hundred seventy patients were included for final analyses. Most of the patients were male (n = 115; 68%) and the average age was 54 years. Using logistic regression analyses, age >55 years [odds ratio (OR): 3.053; P = 0.002], preoperative CRP >15 mg/dL (OR: 2.174; P = 0.027), and preoperative blood sugar >8.3 mmol/L (OR: 3.280; P = 0.001) were independent factors correlated with persistent discharge.

Conclusions:  Older age, elevated preoperative CRP level and blood sugar had a statistically significant association with persistent discharge after operation in deep neck abscesses patients.