bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple functions of the von Willebrand Factor A domain in matrilins: secretion, assembly, and proteolysis
Authors: Zhang Yue , Wang Zheng-ke , Luo Jun-ming , Kanbe Katsuaki , Chen Qian 
Published: June 2008

Abstract
The von Willebrand Factor A (vWF A) domain is one of the most widely distributed structural modules in cell-matrix adhesive molecules such as intergrins and extracellular matrix proteins. Mutations in the vWF A domain of matrilin-3 cause multiple epiphyseal dysplasia (MED), however the pathological mechanism remains to be determined. Previously we showed that the vWF A domain in matrilin-1 mediates formation of a filamentous matrix network through metal-ion dependent adhesion sites in the domain. Here we show two new functions of the vWF A domain in cartilage-specific matrilins (1 and 3). First, vWF A domain regulates oligomerization of matrilins. Insertion of a vWF A domain into matrilin-3 converts the formation of a mixture of matrilin-3 tetramer, trimer, and dimer into a tetramer only, while deletion of a vWF A domain from matrilin-1 converts the formation of the native matrilin-1 trimer into a mixture of trimer and dimer. Second, the vWF A domain protects matrilin-1 from proteolysis. We identified a latent proteolytic site next to the vWF A2 domain in matrilin-1, which is sensitive to the inhibitors of matrix proteases. Deletion of the abutting vWF A domain results in degradation of matrilin-1, presumably by exposing the adjacent proteolytic site. In addition, we also confirmed the vWF A domain is vital for the secretion of matrilin-3. Secretion of the mutant matrilin-3 harbouring a point mutation within the vWF A domain, as occurred in MED patients, is markedly reduced and delayed, resulting from intracellular retention of the mutant matrilin-3. Taken together, our data suggest that different mutations/deletions of the vWF A domain in matrilins may lead to distinct pathological mechanisms due to the multiple functions of the vWF A domain.
Acute bilateral anterior circulation stroke due to anomalous cerebral vasculature: a case report
Authors: Menezes Brian F. , Cheserem Beverley , Kandasamy Jothy , O'Brien Donnacha 
Published: June 2008

Abstract

Introduction
Simultaneous bilateral cerebrovascular infarction is relatively rare and its initial presentation as a space-occupying lesion is extremely uncommon. However, bilateral infarction can result from unilateral occlusion of anomalous cerebral vasculature.

Case presentation
We report the case of a man presenting with lower limb weakness and aphasia of acute onset with initial computerised tomography suggesting bifrontal neoplasm. However, further investigation confirmed bilateral anterior cerebral artery territory infarction with a hypoplastic left anterior cerebral artery with the right anterior cerebral artery supplying both frontal lobes (an anatomical variant). We present the clinical and diagnostic features of this presentation and attempt to ascertain, by reviewing existent medical literature, the frequency and patterns of structural variations in cerebral vasculature.

Conclusion
Simultaneous bilateral cerebral infarction can be the result of a unilateral cerebral artery occlusion and this can potentially mimic a space-occupying lesion. Anomalies of cerebral vasculature are not as rare as is usually believed and this should be borne in mind when investigating unusual presentations of cerebrovascular infarction.
Imatinib for Newly Diagnosed Patients With Chronic Myeloid Leukemia: Incidence of Sustained Responses in an Intention-to-Treat Analysis
Authors: de Lavallade Hugues , Apperley Jane F. , Khorashad Jamshid S. , Milojkovic Dragana , Reid Alistair G. , Bua Marco , Szydlo Richard , Olavarria Eduardo , Kaeda Jaspal , Goldman John M. , Marin David 
Published: June 2008

Purpose Imatinib is remarkably effective in treating newly diagnosed patients with chronic myeloid leukemia (CML) in chronic phase (CP). To date, most of the available data come from a single multicenter study in which some of the patients were censored for diverse reasons. Here, we report our experience in treating patients at a single institution in a setting where all events were recorded. Patients and Methods A total of 204 consecutive adult patients with newly diagnosed CML in CP received imatinib from June 2000 until August 2006. Response (hematologic, cytogenetic, and molecular), progression-free survival (PFS) and survival were evaluated. Results At 5 years, cumulative incidences of complete cytogenetic response (CCyR) and major molecular response (MMR) were 82.7% and 50.1%, respectively. Estimated overall survival and PFS were 83.2% and 82.7%, respectively. By 5 years, 25% of patients had discontinued imatinib treatment because of an unsatisfactory response and/or toxicity. The 5-year probability of remaining in major cytogenetic response while still receiving imatinib was 62.7%. Patients achieving a CCyR at 1 year had a better PFS and overall survival than those failing to reach CCyR, but achieving a MMR conferred no further advantage. The identification of a kinase domain mutation was the only factor predicting for loss of CCyR. Conclusion Imatinib is highly effective in most patients with CML-CP; patients who respond are likely to live substantially longer than those treated with earlier therapies. Achieving CCyR correlated with PFS and overall survival, but achieving MMR had no further predictive value. However, approximately one third of patients still need better therapy.
Early Detection of Pompe Disease by Newborn Screening Is Feasible: Results From the Taiwan Screening Program
Authors: Chien Yin-Hsiu , Chiang Shu-Chuan , Zhang Xiaokui Kate , Keutzer Joan , Lee Ni-Chung , Huang Ai-Chu , Chen Chun-An , Wu Mei-Hwan , Huang Pei-Hsin , Tsai Fu-Jen , Chen Yuan-Tsong , Hwu Wuh-Liang 
Published: June 2008

OBJECTIVE. Pompe disease is an autosomal recessive lysosomal storage disorder that is caused by deficient acid α-glucosidase activity and results in progressive, debilitating, and often life-threatening symptoms involving the musculoskeletal, respiratory, and cardiac systems. Recently, enzyme replacement therapy with alglucosidase α has become possible, but the best outcomes in motor function have been achieved when treatment was initiated early. The aim of this study was to test the feasibility of screening newborns in Taiwan for Pompe disease by using a fluorometric enzymatic assay to determine acid α-glucosidase activity in dried blood spots.
METHODS. We conducted a large-scale newborn screening pilot program between October 2005 and March 2007. The screening involved measuring acid α-glucosidase activity in dried blood spots of ∼45% of newborns in Taiwan. The unscreened population was monitored as a control.
RESULTS. Of the 132 538 newborns screened, 1093 (0.82%) repeat dried blood-spot samples were requested and retested, and 121 (0.091%) newborns were recalled for additional evaluation. Pompe disease was confirmed in 4 newborns. This number was similar to the number of infants who received a diagnosis of Pompe disease in the control group (n = 3); however, newborn screening resulted in an earlier diagnosis of Pompe disease: patients were &lt;1 month old compared with 3 to 6 months old in the control group.
CONCLUSIONS. To our knowledge, this is the first large-scale study to show that newborn screening for Pompe disease is feasible. Newborn screening allows for earlier diagnosis of Pompe disease and, thus, for assessment of the value of an earlier start of treatment.
Lipid and Glucose Alterations in HIV-Infected Children Beginning or Changing Antiretroviral Therapy
Authors: Chantry Caroline J. , Hughes Michael D. , Alvero Carmelita , Cervia Joseph S. , Meyer William A. , Hodge Janice , Borum Peggy , Moye Jack ,   for the PACTG 1010 Team
Published: June 2008

OBJECTIVE. The objective of this study was to describe lipid profiles and glucose homeostasis in HIV-positive children after initiating or changing antiretroviral therapy and their associations with viral, immune, antiretroviral therapy, and growth factor parameters.
METHODS. Ninety-seven prepubertal HIV-positive children aged 1 month to &lt;13 years were observed for 48 weeks after beginning or changing antiretroviral therapy. Fasting lipid panels, serum glucose, insulin, insulin-like growth factor-1 and binding proteins-1 and -3, plasma viral load, and CD4% were measured. Each child was matched on age, gender, and race/ethnicity to children from the National Health and Nutrition Examination Survey, used to give z scores for each child's lipid values. Multivariate regression was used to evaluate the association of changes in z scores over 48 weeks with suppression of HIV-1 RNA, change in CD4% and growth factors, and antiretroviral therapy, adjusted for entry z score, CD4%, log10 HIV-1 RNA, Centers for Disease Control and Prevention category, and total fat and cholesterol dietary intake.
RESULTS. Lipid, apolipoprotein, and insulin levels all increased significantly by 48 weeks. Multivariate analysis of changes demonstrated that increased HDL and decreased total-HDL cholesterol ratio were associated with CD4% increase and with insulin-like growth factor-1, which increased to normal (versus remained stable or became low) over 48 weeks. Total cholesterol levels increased among children who achieved HIV-1 RNA of &lt;400 copies per mL. Antiretroviral therapy regimens that included both a protease inhibitor and a non–nucleoside reverse transcriptase inhibitor were associated with greater increases in total-HDL cholesterol ratio than regimens that contained a protease inhibitor or a non–nucleoside reverse transcriptase inhibitor but not both.
CONCLUSIONS. In these HIV-positive children with predominantly mild-to-moderate disease, initiation or change in antiretroviral therapy was associated with significant increases in multiple lipid measures and insulin resistance. Favorable lipid changes were associated with CD4% increases, suggesting a protective effect of immune reconstitution on atherosclerosis, and with increased insulin-like growth factor-1 levels, supporting the theory that reduced growth hormone resistance may be a mechanism by which lipid profiles are improved. Finally, antiretroviral therapy regimens that contain both a non–nucleoside reverse transcriptase inhibitor and a protease inhibitor are associated with worse lipid profiles than regimens that contain 1 but not both of these drug classes.
Assessment of an approach to estimating aquatic bioconcentration factors using reduced sampling
Authors: Springer Timothy A , Guiney Patrick D , Krueger Henry O , Jaber Mark J 
Published: June 2008

Abstract
For a broad range of circumstances, we show that reliable bioconcentration factor (BCF) estimates can be made using a study design that is based on standard regulatory guideline test procedures but that uses significantly fewer animals and resources. This minimized design involves taking tissue samples only twice during a 14-d depuration period. The utility of the minimized test design was first assessed by resampling data from a series of standard guideline tests and calculating the BCF estimates that would have been obtained if the test had been performed using the minimized design. Data from 25 bioconcentration curves giving BCF estimates ranging from approximately 0.3 to over 20,000 were used. The correlation of log BCF estimates from the guideline study with log BCF estimates from the simulated minimized tests was r2 = 0.99, and the slope of the regression line was 0.96. The robustness of BCF estimates to random variation in measurement of chemicals in fish and water (coefficients of variation of concentrations ranging up to 25%) was evaluated using Monte Carlo simulations. For chemicals with depuration half-lives of less than the length of the depuration period, median BCF estimates from the Monte Carlo simulations of the minimized design were always within 7% of the true BCF. The ratio of the 95th to the 5th percentile BCF estimates was always less than or equal to 3.7. Furthermore, the span from the 95th to the 5th percentile of BCF estimates was only 15% wider in the minimized test than in the full guideline test, even though animal use and analytical effort was markedly reduced.
Atrazine and increased male production byDaphnia: The importance of combining field and laboratory approaches
Authors: Stoeckel James A , González María J , Oris James T , Kovach Mathew J , Mace Kimberly M 
Published: June 2008

AbstractAtrazine is one of the most commonly applied herbicides in North America and annually pulses through many midwestern stream and reservoir systems. Previous studies have yielded conflicting results regarding the ability of atrazine to stimulate male production by Daphnia, an effect hypothesized to lower population growth rates during a period of intense larval fish predation. In the present study, populations of Daphnia parvula and Daphnia ambigua exhibited high proportions of males but no ephippial females when atrazine pulsed into Acton Lake, a small midwestern reservoir. Field results thus supported the hypothesis of excess male production by Daphnia during the spring herbicide pulse. In laboratory studies, dose–response studies, and population-level assays revealed no effect of atrazine on male production or population growth rate of multiple clones differing in reproductive strategy and exposure history. However, D. parvula increased male production in response to an endogenous crustacean hormone (methyl farnesoate). Excess male production observed in the field population was therefore not likely caused by atrazine, although we cannot rule out the possibility of interactive effects of atrazine and some other stressor. Apparent signs of endocrine disruption in the presence of high concentrations of a suspected agent should be viewed with caution in the absence of parallel laboratory studies involving individuals from the populations of interest.
Making species salinity sensitivity distributions reflective of naturally occurring communities: Using rapid testing and Bayesian statistics
Authors: Hickey Graeme L , Kefford Ben J , Dunlop Jason E , Craig Peter S 
Published: June 2008

Abstract
Species sensitivity distributions (SSDs) may accurately predict the proportion of species in a community that are at hazard from environmental contaminants only if they contain sensitivity data from a large sample of species representative of the mix of species present in the locality or habitat of interest. With current widely accepted ecotoxicological methods, however, this rarely occurs. Two recent suggestions address this problem. First, use rapid toxicity tests, which are less rigorous than conventional tests, to approximate experimentally the sensitivity of many species quickly and in approximate proportion to naturally occurring communities. Second, use expert judgements regarding the sensitivity of higher taxonomic groups (e.g., orders) and Bayesian statistical methods to construct SSDs that reflect the richness (or perceived importance) of these groups. Here, we describe and analyze several models from a Bayesian perspective to construct SSDs from data derived using rapid toxicity testing, combining both rapid test data and expert opinion. We compare these new models with two frequentist approaches, Kaplan–Meier and a log-normal distribution, using a large data set on the salinity sensitivity of freshwater macroinvertebrates from Victoria (Australia). The frequentist log-normal analysis produced a SSD that overestimated the hazard to species relative to the Kaplan–Meier and Bayesian analyses. Of the Bayesian analyses investigated, the introduction of a weighting factor to account for the richness (or importance) of taxonomic groups influenced the calculated hazard to species. Furthermore, Bayesian methods allowed us to determine credible intervals representing SSD uncertainty. We recommend that rapid tests, expert judgements, and novel Bayesian statistical methods be used so that SSDs reflect communities of organisms found in nature.
High within-individual variation in total mercury concentration in seabird feathers
Authors: Bond Alexander L , Diamond Antony W 
Published: June 2008

Abstract
To our knowledge, no rigorous assessment of the variation in mercury concentrations within individual seabirds has been made using multiple body feathers. We analyzed five feathers from individual Arctic terns (Sterna paradisaea Pontoppidan), common terns (Sterna hirundo L.), and Leach's storm-petrels (Oceanodroma leucorhoa Veillot) and found levels of within-individual variability higher than population or time-series variation. Using a randomization procedure, we found a large range of possible mercury concentrations if only one feather per individual had been sampled. Researchers should report within-individual variability in future studies.
The S. japonicum-Based pGEX Vector: Commercial Outcomes from Analysis of Model Host-Parasite Relationships in a “North-South” Collaboration
Authors: Mitchell Graham F. , Davern Kathy M. , Tiu Wilfred U. 
Published: June 2008

As judged by widespread utility in protein production from recombinant Escherichia coli and by the magnitude
of royalty payments to Melbourne’s Walter & Eliza Hall Institute (WEHI), the expression vector pGEX, invented by Dr
Donald Smith, has been a significant commercial success. It is based on the 26kDa glutathione S-transferase of Schisto-soma japonicum(Philippines) termed Sj26GST, that emerged from work throughout the 1980’s on resistance to infection in a peculiar mouse strain, WEHI 129/J. Sj26GST was the lead vaccine candidate for this human helminth worm being pursued in a long-term collaboration between WEHI in Australia and Dr Edito Garcia’s1group at the College of Public
Health, University of the Philippines in Manila that commenced in 1980.
The product, pGEX, is an excellent example of commercial spin-off from basic research in mouse model systems that indeed
evolved into an applied research program but with a very different goal, namely rational molecular vaccine development.
Role of Central Nervous System Glucagon-Like Peptide-1 Receptors in Enteric Glucose Sensing
Authors: Knauf Claude , Cani Patrice D. , Kim Dong-Hoon , Iglesias Miguel A. , Chabo Chantal , Waget Aurélie , Colom André , Rastrelli Sophie , Delzenne Nathalie M. , Drucker Daniel J. , Seeley Randy J. , Burcelin Remy 
Published: June 2008

OBJECTIVE—Ingested glucose is detected by specialized sensors in the enteric/hepatoportal vein, which send neural signals to the brain, which in turn regulates key peripheral tissues. Hence, impairment in the control of enteric-neural glucose sensing could contribute to disordered glucose homeostasis. The aim of this study was to determine the cells in the brain targeted by the activation of the enteric glucose-sensing system.
RESEARCH DESIGN AND METHODS—We selectively activated the axis in mice using a low-rate intragastric glucose infusion in wild-type and glucagon-like peptide-1 (GLP-1) receptor knockout mice, neuropeptide Y–and proopiomelanocortin–green fluorescent protein–expressing mice, and high-fat diet diabetic mice. We quantified the whole-body glucose utilization rate and the pattern of c-Fos positive in the brain.
RESULTS—Enteric glucose increased muscle glycogen synthesis by 30% and regulates c-Fos expression in the brainstem and the hypothalamus. Moreover, the synthesis of muscle glycogen was diminished after central infusion of the GLP-1 receptor (GLP-1Rc) antagonist Exendin 9-39 and abolished in GLP-1Rc knockout mice. Gut-glucose–sensitive c-Fos–positive cells of the arcuate nucleus colocalized with neuropeptide Y–positive neurons but not with proopiomelanocortin-positive neurons. Furthermore, high-fat feeding prevented the enteric activation of c-Fos expression.
CONCLUSIONS—We conclude that the gut-glucose sensor modulates peripheral glucose metabolism through a nutrient-sensitive mechanism, which requires brain GLP-1Rc signaling and is impaired during diabetes.
Longitudinal Association of Glucose Metabolism With Retinopathy
Authors: Tapp Robyn J. , Tikellis Gabriella , Wong Tien Y. , Harper C. Alex , Zimmet Paul Z. , Shaw Jonathan E. ,   on behalf of the Australian Diabetes Obesity and Lifestyle Study Group
Published: June 2008

OBJECTIVE—We determined the longitudinal association of glucose metabolism with retinopathy in a sample of the Australian population.
RESEARCH DESIGN AND METHODS—The Australian Diabetes Obesity and Lifestyle (AusDiab) study is a national, longitudinal study of adults aged ≥25 years from 42 randomly selected areas of Australia. Retinopathy was assessed at baseline in 1999–2000 and 5 years later in 2004–2005 in participants identified as having diabetes (based on self-report and oral glucose tolerance test) and impaired glucose metabolism and in a random sample with normal glucose tolerance. Complete retinal data were available for 1,192 participants. Photographs were graded at two time points according to a simplified version of the Wisconsin grading system.
RESULTS—The 5-year incidences of retinopathy were 13.9 and 3.0% among those with known and newly diagnosed diabetes at baseline, respectively. Of those who developed incident newly diagnosed diabetes at follow-up, 11.9% had retinopathy at baseline compared with 5.6% of those who did not progress to incident newly diagnosed diabetes (P = 0.037). After adjustment for factors identified as risk factors for diabetes, individuals with retinopathy signs at baseline were twice as likely to develop incident newly diagnosed diabetes compared with those who did not have retinopathy signs at baseline.
CONCLUSIONS—The 5-year incidence of retinopathy was 13.9% among individuals with known diabetes. Nondiabetic individuals with retinopathy signs at baseline had a twofold higher risk of developing incident newly diagnosed diabetes 5 years later. This result provides further evidence that mild retinopathy signs may be a preclinical marker of underlying microvascular disease and future diabetes risk.
Diabetes Complications in Youth
Authors: Buckloh Lisa M. , Lochrie Amanda S. , Antal Holly , Milkes Amy , Canas J. Atilio , Hutchinson Sally , Wysocki Tim 
Published: June 2008

OBJECTIVE—Youth with type 1 diabetes face long-term risks of health complications of the disease. Little is known about patients’ and parents’ knowledge, acquisition of information, and family communication regarding these complications. This paper reports qualitative analyses of parental focus-group discussions of this topic.
RESEARCH DESIGN AND METHODS—A total of 47 participants (30 mothers, 14 fathers, and 3 others) representing 33 children between the ages of 8 and 18 years with type 1 diabetes participated in 1 of 13 focus groups. Open-ended questions focused on the type and amount of information about long-term complications presented to parents by health care professionals at different time points, as well as the way that information was presented. Questions also elicited details about parent-child communication and exposure to misconceptions about diabetes complications.
RESULTS—Qualitative analysis of the transcribed focus groups revealed that participants experienced significant anxiety about diabetes complications, with a shift from concern about daily management tasks to concern about long-term complications over time. Participants desired a flexible, collaborative educational approach, especially regarding the timing and type of information, relative to the child's age and duration of diabetes. Many parents wanted more sensitive communication and emotional support from health care providers. Motivating children appeared to be a particular challenge; family burnout with regard to diabetes care over time was reported. Knowledge was gained in many ways, yet misinformation was uncommon.
CONCLUSIONS—Obtaining information about long-term complications is an important process that changes over the course of the disease and with the child's developmental level. More research is needed, especially regarding youth knowledge, learning, and beliefs about diabetes complications.