bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetic and thermodynamic parameters for heat denaturation of human recombinant lactoferrin from rice1This article is part of a Special Issue entitled Lactoferrin and has undergone the Journal's usual peer review process.
Authors: Castillo Eduardo , Pérez María Dolores , Franco Indira , Calvo Miguel , Sánchez Lourdes 
Published: May 2012

Heat denaturation of recombinant human lactoferrin (rhLf) from rice with 3 different iron-saturation degrees, holo rhLf (iron-saturated), AsIs rhLf (60% iron saturation), and apo rhLf (iron-depleted), was studied. The 3 forms of rhLf were subjected to heat treatment, and the kinetic and thermodynamic parameters of the denaturation process were determined. Thermal denaturation of rhLf was assessed by measuring the loss of reactivity against specific antibodies. Dt values (time to reduce 90% of immunoreactivity) decreased with increasing temperature of treatment for apo and holo rhLf, those values being higher for the iron-saturated form, which indicates that iron confers thermal stability to rhLf. However, AsIs rhLf showed a different behaviour with an increase in resistance to heat between 79 °C and 84 °C, so that the kinetic parameters could not be calculated. The heat denaturation process for apo and holo rhLf was best described assuming a reaction order of 1.5. The activation energy of the denaturation process was 648.20 kJ/mol for holo rhLf and 406.94 kJ/mol for apo rhLf, confirming that iron-depleted rhLf is more sensitive to heat treatment than iron-saturated rhLf.
Biochemical and molecular impacts of lactoferrin on small intestinal growth and development during early life1This article is part of a Special Issue entitled Lactoferrin and has undergone the Journal's usual peer review process.
Authors: Liao Yalin , Jiang Rulan , Lönnerdal Bo 
Published: May 2012

Postnatal modeling of the intestinal epithelium has long-term impacts on the healthy development of infants and relies largely on nutrient composition of the diet. Lactoferrin (Lf) is among the various human milk trophic factors that facilitate the infant intestinal adaptation. Hydrolysis of Lf is minimal at the prevailing postprandial pH of infants, and Lf may therefore have greater biological potential in infants than in adults. Lf bidirectionally stimulates concentration-dependent proliferation and differentiation of small intestinal epithelial cells, and therefore affects small intestinal mass, length, and epithelial digestive enzyme expression. A 105 kDa Lf receptor (LfR) specifically mediates the uptake of Lf into enterocytes and crypt cells. Mechanistically, the complex of Lf and LfR is internalized through clathrin-mediated endocytosis; both iron-free apo-Lf and iron-saturated holo-Lf activate the PI3K/Akt pathway, whereas only apo-Lf triggers ERK1/2 signaling. Lf enters the nucleus, where it can stimulate thymidine incorporation into crypt cells, regulating transcription of genes such as TGF-β1. In the fetus, the plasma membrane LfR is at the highest abundance in the small intestine, and the receptor gene is tightly controlled at multiple levels. Aspecific microRNA, miR-584, is involved in the posttranscriptional regulation of LfR, and in the human LfR DNA promoter, 2 Sp1 binding sites have been characterized functionally. Finally, cell proliferation and global gene expression reveal that native bovine Lf can perform biological activities similar to those exerted by human Lf in postnatal small intestinal development.
Transgenic milk containing recombinant human lactoferrin modulates the intestinal flora in piglets1This article is part of a Special Issue entitled Lactoferrin and has undergone the Journal’s usual peer review process.
Authors: Hu Wenping , Zhao Jie , Wang Jianwu , Yu Tian , Wang Jing , Li Ning 
Published: May 2012

Lactoferrin (LF) is a beneficial multifunctional protein in milk. The objective of this study was to determine whether bovine transgenic milk containing recombinant human lactoferrin (rhLF) can modulate intestinal flora in the neonatal pig as an animal model for the human infant. We fed 7-day-old piglets (i) ordinary whole milk (OM), (ii) a 1:1 mixture of OM and rhLF milk (MM), or (iii) rhLF milk (LFM). LFM provided better average daily mass gain than OM (P = 0.007). PCR–denaturing gradient gel electrophoresis and 16S rDNA sequencing analysis revealed that the LFM piglets exhibited more diversity of the intestinal flora than the OM group. Except for the colon in the LFM group, an increasing trend in microbial diversity occurred from the duodenum to the colon. Fecal flora was not different across different ages or different treatment groups, but a cluster analysis showed that the fecal flora of OM- and MM-fed piglets had a higher degree of similarity than that of LFM-fed piglets. Based on culture-based bacterial counts of intestinal content samples, concentrations of Salmonella spp. in the colon and of Escherichia coli throughout the intestine were reduced with LFM (P < 0.01). Concentrations of Bifidobacterium spp. in the ileum and of Lactobacillus spp. throughout the intestine were also increased with LFM (P ≤ 0.01). We suggest that rhLF can modulate the intestinal flora in piglets.
Oral lactoferrin treatment resolves amoebic intracecal infection in C3H/HeJ mice1This article is part of a Special Issue entitled Lactoferrin and has undergone the Journal’s usual peer review process.
Authors: León-Sicairos Nidia , Martínez-Pardo Leonardo , Sánchez-Hernández Beatriz , de la Garza Mireya , Carrero Julio César 
Published: May 2012

Entamoeba histolytica is a protozoan parasite that causes amoebiasis, an illness that affects many people around the world. We have previously reported that lactoferrin is able to kill E. histolytica in in vitro cultures. The aim of the present study was to evaluate the therapeutic effect of orally administered bovine lactoferrin in the control of intestinal amoebiasis of susceptible C3H/HeJ mice. The results showed that 20 mg lactoferrin/kg orally administered each day for 1 week was able to eliminate the infection in 63% of the mice, since neither trophozoites nor evidence of epithelial damage and (or) swelling were found in tissue sections of the cecum. The rest of the treated animals (37%) showed a decrease in trophozoite numbers and mucus secreted to the lumen, as compared with untreated and infected mice (p < 0.05). By immunohistochemistry, the profile of secreted cytokines in the cecum revealed that infected but untreated animals showed a mixed Th1/regulatory cytokines profile, whereas the cecum of mice treated (cured) showed a Th2 cytokine profile (IL-4) and expression of the multifunctional IL-6. In addition, cytokines and increasing cecal production of total IgA antibodies were found associated with little inflammation and disease control observed in the cecum of lactoferrin-treated animals. These results suggest that oral administration of lactoferrin can control intestinal amoebic infection probably by killing amoebas or favoring their removal and reestablish the antiinflammatory intestinal environment.
Lactoferrin, a bird’s eye view
Authors: Vogel Hans J. 
Published: May 2012

Lactoferrin is an abundant iron-binding protein in milk. This 80 kDa bilobal glycoprotein is also present in several other secreted bodily fluids, as well as in the secondary granules of neutrophils. The potent iron-binding properties of lactoferrin can locally create iron deficiency, and this is an important factor in host defense as it prevents bacteria from growing and forming biofilms. In addition to having antibacterial activity, lactoferrin is now known to have a long list of other beneficial biological properties. It has direct antiviral, antifungal, and even some anticancer activities. It can also promote wound healing and bone growth, or it can act as an iron carrier. Moreover, lactoferrin displays a cytokine-like “alarmin” activity, and it activates the immune system. Simultaneously, it can bind endotoxin (lipopolysaccharide), and in doing so, it modulates the activity of the host immune response. The majority of these intriguing biological activities reside in the unique positively charged N-terminal region of the protein. Interestingly, several peptides, which retain many of the beneficial activities, can be released from this region of lactoferrin. An isoform of the human protein, known as delta-lactoferrin, is expressed inside many cells, where it acts as a transcription factor. Lactoferrin purified from human and bovine milk have very similar but not completely identical properties. Lactoferrin receptors have been identified on the surface of various cells, and some of these can bind both the human and the bovine protein. Because of the extensive health-promoting effects of lactoferrin, there has been considerable interest in the use of bovine or human lactoferrin as a “protein nutraceutical” or as a therapeutic protein. When lactoferrin is used as a “biologic drug”, it seems to be orally active in contrast to most other therapeutic proteins.
Lactoferrin – 50 years on
Authors: Brock Jeremy H. 
Published: May 2012

It is now some 50 years since iron-binding lactoferrin was first isolated and purified, an event that opened the way to subsequent extensive research on lactoferrin structure and function. The initial recognition that lactoferrin closely resembled the plasma iron-transport protein transferrin meant that lactoferrin was first thought to mediate intestinal iron absorption or to act as an antimicrobial agent. It was also suggested that it could mediate the hyposideraemia of inflammation. This paper will assess to what extent early proposals have stood the test of time and also suggest possible mechanisms by which lactoferrin can mediate the large number of potential functions that have subsequently been proposed. It will also review the ability of lactoferrin to resist digestion in the gastrointestinal tract and identify areas for future research.
Prospective Study of Changes in the Metabolomic Profiles of Men during Their First Three Months of Androgen Deprivation Therapy for Prostate Cancer
Authors: Saylor Philip J. , Karoly Edward D. , Smith Matthew R. 
Published: May 2012

Abstract
Purpose: Androgen deprivation therapy (ADT) for prostate cancer causes an increase in fasting insulin and adverse changes in body composition and serum lipid profile. It is unknown what other metabolic alterations are caused by ADT. To better characterize the metabolic effects of ADT, we measured changes in plasma metabolomic profile at baseline and after the first 3 months of therapy.
Experimental Design: Fasting plasma samples were drawn from 36 subjects at baseline and after 3 months of gonadotropin releasing hormone (GnRH) agonist therapy. Extracted samples were split into equal parts for analysis on the gas chromatography-mass spectrometry and liquid chromatography/tandem mass spectrometry platforms.
Results: Of the 292 identified metabolites, 56 changed significantly (P &lt; 0.05) from baseline to 3 months. Notable changes were grouped as follows: (i) Multiple steroids were lower at 3 months, consistent with the effect of therapy on gonadal androgen synthesis. (ii) Most bile acids and their metabolites were higher during treatment. Cholesterol levels changed very little. (iii) Markers of lipid beta-oxidation (acetyl-carnitines and ketone bodies) and omega-oxidation were lower at 3 months. (iv) Two previously identified biomarkers of insulin resistance (2-hydroxybutyrate and branch chain keto-acid dehydrogenase complex products) were stable to lower at 3 months.
Conclusions: Unbiased metabolomic analyses revealed expected, novel, and unexpected results. Steroid levels fell, consistent with the effects of ADT. Most bile acids and their metabolites increased during ADT, a novel finding. Biomarkers of lipid metabolism and insulin resistance fell, unexpected given that ADT has been shown to increase fasting insulin. Clin Cancer Res; 18(13); 3677–85. ©2012 AACR.
Development of a Human Monoclonal Antibody for Potential Therapy of CD27-Expressing Lymphoma and Leukemia
Authors: Vitale Laura A. , He Li-Zhen , Thomas Lawrence J. , Widger Jennifer , Weidlick Jeffrey , Crocker Andrea , O'Neill Thomas , Storey James , Glennie Martin J. , Grote Deanna M. , Ansell Stephen M. , Marsh Henry , Keler Tibor 
Published: May 2012

AbstractPurpose: The TNF receptor superfamily member CD27 is best known for its important role in T-cell immunity but is also recognized as a cell-surface marker on a number of B- and T-cell malignancies. In this article, we describe a novel human monoclonal antibody (mAb) specific for CD27 with properties that suggest a potential utility against malignancies that express CD27.Experimental Design: The fully human mAb 1F5 was generated using human Ig transgenic mice and characterized by analytical and functional assays in vitro. Severe combined immunodeficient (SCID) mice inoculated with human CD27-expressing lymphoma cells were administered 1F5 to investigate direct antitumor effects. A pilot study of 1F5 was conducted in non-human primates to assess toxicity.Results: 1F5 binds with high affinity and specificity to human and macaque CD27 and competes with ligand binding. 1F5 activates T cells only in combination with T-cell receptor stimulation and does not induce proliferation of primary CD27-expressing tumor cells. 1F5 significantly enhanced the survival of SCID mice bearing Raji or Daudi tumors, which may be mediated through direct effector mechanisms such as antibody-dependent cellular cytotoxicity. Importantly, administration of up to 10 mg/kg of 1F5 to cynomolgus monkeys was well tolerated without evidence of significant toxicity or depletion of circulating lymphocytes.Conclusions: Collectively, the data suggest that the human mAb 1F5, which has recently entered clinical development under the name CDX-1127, may provide direct antitumor activity against CD27-expressing lymphoma or leukemia, independent of its potential to enhance immunity through its agonistic properties. Clin Cancer Res; 18(14); 3812–21. ©2012 AACR.
Prediction of Incident Heart Failure in General Practice
Authors: Agarwal Sunil K. , Chambless Lloyd E. , Ballantyne Christie M. , Astor Brad , Bertoni Alain G. , Chang Patricia P. , Folsom Aaron R. , He Max , Hoogeveen Ron C. , Ni Hanyu , Quibrera Pedro M. , Rosamond Wayne D. , Russell Stuart D. , Shahar Eyal , Heiss Gerardo 
Published: May 2012

Background—
A simple and effective heart failure (HF) risk score would facilitate the primary prevention and early diagnosis of HF in general practice. We examined the external validity of existing HF risk scores, optimized a 10-year HF risk function, and examined the incremental value of several biomarkers, including N-terminal pro-brain natriuretic peptide.

Methods and Results—
During 15.5 years (210 102 person-years of follow-up), 1487 HF events were recorded among 13 555 members of the biethnic Atherosclerosis Risk in Communities (ARIC) Study cohort. The area under curve from the Framingham-published, Framingham-recalibrated, Health ABC HF recalibrated, and ARIC risk scores were 0.610, 0.762, 0.783, and 0.797, respectively. On addition of N-terminal pro-brain natriuretic peptide, the optimism-corrected area under curve of the ARIC HF risk score increased from 0.773 (95% CI, 0.753–0.787) to 0.805 (95% CI, 0.792–0.820). Inclusion of N-terminal pro-brain natriuretic peptide improved the overall classification of recalibrated Framingham, recalibrated Health ABC, and ARIC risk scores by 18%, 12%, and 13%, respectively. In contrast, cystatin C or high-sensitivity C-reactive protein did not add toward incremental risk prediction.

Conclusions—
The ARIC HF risk score is more parsimonious yet performs slightly better than the extant risk scores in predicting 10-year risk of incident HF. The inclusion of N-terminal pro-brain natriuretic peptide markedly improves HF risk prediction. A simplified risk score restricted to a patient’s age, race, sex, and N-terminal pro-brain natriuretic peptide performs comparably to the full score (area under curve, 0.745) and is suitable for automated reporting from laboratory panels and electronic medical records.
Predictors of Self-Report of Heart Failure in a Population-Based Survey of Older Adults
Authors: Gure Tanya R. , McCammon Ryan J. , Cigolle Christine T. , Koelling Todd M. , Blaum Caroline S. , Langa Kenneth M. 
Published: May 2012

Background—
Little research has been conducted on the predictors of self-report or patient awareness of heart failure (HF) in a population-based survey. The objective of this study was to (1) test the agreement between Medicare administrative and Health and Retirement Study (HRS) survey data and (2) determine predictors associated with self-report of HF, using a validated Medicare claims algorithm as the reference standard. We hypothesized that those who self-reported HF were more likely to have a higher number of HF-related claims.

Methods and Results—
Secondary data analysis was conducted using the 2004 wave of the HRS linked to 2002 to 2004 Medicare claims (n=5573 respondents aged ≥67 years). Concordance between self-report of HF in the HRS and Medicare claims was calculated. Logistic regression was performed to identify predictors associated with self-report HF. HF prevalence by self-report was 4.6%. Self-report of HF and claims agreement was 87% (κ=0.34). The presence of >1 HF inpatient claims was associated with greater odds of self-report (odds ratio [OR], 1.92; 95% CI, 1.23–3.00). Greater odds of self-reporting HF was also associated with ≥4 HF claims (OR, 2.74; 95% CI, 1.36–5.52). Blacks (OR, 0.28; 95% CI, 0.14–0.55) and Hispanics (OR, 0.30; 95% CI, 0.11–0.83) were less likely to self-report HF compared with whites in the final model.

Conclusions—
Self-report of HF is an insensitive method for accurately identifying HF cases, especially in those with less-severe disease and who are nonwhite. There may be limited awareness of HF among older minority patients despite having clinical encounters during which HF is coded as a diagnosis.
Transfer Times and Outcomes in Patients With ST-Segment–Elevation Myocardial Infarction Undergoing Interhospital Transfer for Primary Percutaneous Coronary Intervention
Authors: van Diepen Sean , Widimský Petr , Lopes Renato D. , White Kyle R. , Weaver W. Douglas , Van de Werf Frans , Ardissino Diego , van’t Hof Arnoud W.J. , Armstrong Paul W. , Granger Christopher B. 
Published: May 2012

Background—
Transfer delays for primary percutaneous coronary intervention may increase mortality in patients with ST-segment–elevation myocardial infarction. We examined the association between door 1-to–door 2 (D1D2) time, a measure capturing the entire transfer process, and outcomes in patients undergoing interhospital transfer for primary percutaneous coronary intervention.

Methods and Results—

We evaluated the relationship between D1D2 time and the 90-day incidence of death, shock, and heart failure in the subset of 2075 (36.1%) of 5745 patients who underwent interhospital transfer for primary percutaneous coronary intervention in the Assessment of Pexelizumab in Acute Myocardial Infarction trial. There was no significant difference in the 90-day incidence of death, shock, and heart failure between the transferred and the nontransferred groups (10.3% versus 10.2%;
P
= 0.89). The median difference in symptom-to–balloon time between the 2 groups was 45 minutes (229 versus 184;
P
<0.001). The primary outcome per 30-minute delay was higher for patients with a D1D2 time ≤150 minutes (hazard ratio, 1.19: 95% confidence interval, 1.06 to 1.33;
P
= 0.004) but not for D1D2 times >150 minutes (hazard ratio, 0.99: 95% confidence interval, 0.96 to 1.02;
P
= 0.496). The association between longer D1D2 time and worsening outcome was no longer statistically significant after multivariable adjustment.

Conclusions—
Longer transfer times were associated with higher rate of death, shock, and heart failure among patients undergoing interhospital transfer from primary percutaneous coronary intervention, although this difference did not persist after adjusting for baseline characteristics.
Planimetric Hematoma Measurement in Patients With Intraventricular Hemorrhage
Authors: Dowlatshahi Dar , Kosior Jayme C. , Idris Sherif , Eesa Muneer , Dickhoff Peter , Joshi Manish , Subramaniam Suresh , Tymchuk Sarah , Hill Michael D. , Aviv Richard I. , Frayne Richard , Demchuk Andrew M. 
Published: May 2012

Background and Purpose—
Reliable quantification of both intracerebral hemorrhage and intraventricular hemorrhage (IVH) volume is important for hemostatic trials. We evaluated the reliability of computer-assisted planimetric volume measurements of IVH.

Methods—
Computer-assisted planimetry was used to quantify IVH volume. Five raters measured IVH volumes, total (intracerebral hemorrhage+IVH) volumes, and Graeb scores from 20 randomly selected computed tomography scans twice. Estimates of interrater and intrarater reliability were calculated and expressed as an intrarater correlation coefficient and an absolute minimum detectable difference.

Results—
Planimetric IVH volume analysis had excellent intra- and interrater agreement (intrarater correlation coefficient, 0.96 and 0.92, respectively), which was superior to the Graeb score (intrarater correlation coefficient, 0.88 and 0.83). Minimum detectable differences for intra- and interrater volumes were 12.1 mL and 17.3 mL, and were dependent on the total size of the hematoma; hematomas smaller than the median 43.8 mL had lower minimum detectable differences, whereas those larger than the median had higher minimum detectable differences. Planimetric total hemorrhage volume analysis had the best intra- and interrater agreement (intrarater correlation coefficient, 0.99 and 0.97, respectively).

Conclusions—
Computer-assisted planimetric techniques provide a reliable measurement of ventricular hematoma volume, but are susceptible to higher absolute error when assessing larger hematomas.
Simulating the Regional Impacts of Urbanization and Anthropogenic Heat Release on Climate across China
Authors: Feng Jin-Ming , Wang Yong-Li , Ma Zhu-Guo , Liu Yong-He 
Published: May 2012

Abstract
Together with economic development and accelerated urbanization, the urban population in China has been increasing rapidly, and anthropogenic heat released by large-scale energy consumption in cities is expected to be a vital factor affecting the climate. In this paper, the Weather Research and Forecasting (WRF) model coupled with the Urban Canopy Model (UCM) is employed to simulate the regional impacts on climate under the two scenarios: the underlying surface changes due to urbanization (USCU) and anthropogenic heat release (AHR). Three experiments were performed from December 2006 to December 2008. With respect to the USCU, the surface albedo and the available surface soil water decrease markedly. With the inclusion of AHR, the two scenarios give rise to increased surface temperatures over most areas of China. Especially in the urban agglomeration area of the Yangtze River delta, the combination of USCU and AHR could result in an increase of 2°C in the surface air temperature. The influence of AHR on surface air temperature in winter is greater than the influence of USCU without considering any extra sources of heat, but the opposite is found in summer. The combination of USCU and AHR leads to changes in the surface energy budget. They both increase sensible heat flux, but USCU decreases latent heat flux significantly, and AHR increases latent heat flux slightly. Nevertheless, under the influence of these two scenarios, the precipitation increases in some areas, especially in the Beijing–Tianjin–Hebei region, while it decreases in other areas, most notably the Yangtze River delta.