bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population Pharmacokinetics of Tigecycline in Patients with Complicated Intra-Abdominal or Skin and Skin Structure Infections
Authors: Van Wart S. A. , Owen J. S. , Ludwig E. A. , Meagher A. K. , Korth-Bradley J. M. , Cirincione B. B. 
Published: October 2006

ABSTRACT

Tigecycline, a first-in-class expanded glycylcycline antimicrobial agent, has demonstrated efficacy in the treatment of complicated skin and skin structure infections (cSSSI) and complicated intra-abdominal (cIAI) infections. A population pharmacokinetic (PK) model for tigecycline was developed for patients with cSSSI or cIAI enrolled in two phase 2 clinical trials, and the influence of selected demographic factors and clinical laboratory measures was investigated. Tigecycline was administered as an intravenous loading dose followed by a 0.5- or 1-h infusion every 12 h for up to 14 days. Blood samples were collected the day before or the day of hospital discharge for the determination of serum tigecycline concentrations. Patient covariates were evaluated using stepwise forward (α = 0.05) and backward (α = 0.001) procedures. The predictive performance of the model was assessed separately using pooled data from either two phase 3 studies for patients with cSSSI or two phase 3 studies for patients with cIAI. A two-compartment model with zero-order input and first-order elimination adequately described the steady-state tigecycline concentration-time data. Tigecycline clearance was shown to increase with increasing weight, increasing creatinine clearance, and male gender (
P
< 0.001). The final model provided a relatively unbiased fit to each data set. Individual predicted values of the area under the concentration-time curve from 0 to 12 h (AUC
0-12
) were generally unbiased (median prediction error, −1.60% to −3.78%) and were similarly precise (median absolute prediction error, <4%) when compared across data sets. The population PK model provided the basis to obtain individual estimates of steady-state AUC
0-12
in later exposure-response analyses of tigecycline safety and efficacy in patients with cSSSI or cIAI.
Metformin Is an AMP Kinase–Dependent Growth Inhibitor for Breast Cancer Cells
Authors: Zakikhani Mahvash , Dowling Ryan , Fantus I. George , Sonenberg Nahum , Pollak Michael 
Published: October 2006

Abstract
Recent population studies provide clues that the use of metformin may be associated with reduced incidence and improved prognosis of certain cancers. This drug is widely used in the treatment of type 2 diabetes, where it is often referred to as an “insulin sensitizer” because it not only lowers blood glucose but also reduces the hyperinsulinemia associated with insulin resistance. As insulin and insulin-like growth factors stimulate proliferation of many normal and transformed cell types, agents that facilitate signaling through these receptors would be expected to enhance proliferation. We show here that metformin acts as a growth inhibitor rather than an insulin sensitizer for epithelial cells. Breast cancer cells can be protected against metformin-induced growth inhibition by small interfering RNA against AMP kinase. This shows that AMP kinase pathway activation by metformin, recently shown to be necessary for metformin inhibition of gluconeogenesis in hepatocytes, is also involved in metformin-induced growth inhibition of epithelial cells. The growth inhibition was associated with decreased mammalian target of rapamycin and S6 kinase activation and a general decrease in mRNA translation. These results provide evidence for a mechanism that may contribute to the antineoplastic effects of metformin suggested by recent population studies and justify further work to explore potential roles for activators of AMP kinase in cancer prevention and treatment. (Cancer Res 2006; 66(21): 10269-73)
Preparing the “Soil”: The Primary Tumor Induces Vasculature Reorganization in the Sentinel Lymph Node before the Arrival of Metastatic Cancer Cells
Authors: Qian Chao-Nan , Berghuis Bree , Tsarfaty Galia , Bruch MaryBeth , Kort Eric J. , Ditlev Jon , Tsarfaty Ilan , Hudson Eric , Jackson David G. , Petillo David , Chen Jindong , Resau James H. , Teh Bin Tean 
Published: October 2006

Abstract
Sentinel lymph node (SLN) metastasis is the first step in the spreading of cancer in many malignancies. Tumor-reactive lymphadenopathy in SLNs has been observed for decades, but alterations of the lymphatic channels and vasculature in these nodes before the arrival of metastatic tumor cells remain unexplored. Using animal models, we show here that, before the establishment of metastasis in the SLN, there are reorganizations of the lymphatic channels and the vasculature. The node becomes a functional blood vessel–enriched and lymph vessel/sinus-enriched organ before metastasis. The enlargement of the lymph sinuses is correlated with the primary tumor weight. The newly emerged functional blood vessels develop from high endothelial venules (HEV), in which the proliferation rate of the endothelial cells is also significantly increased. Similar alterations of the HEVs are also characterized in the axillary lymph nodes from human breast cancer patients without the evidence of metastasis. These findings support the hypothesis that modification of the microenvironment for a secondary tumor (i.e., vasculature reorganization in the SLN) can be initiated by a primary tumor before and independent of the physical presence of metastatic cancer cells. (Cancer Res 2006; 66(21): 10365-76)
Saving and Life Insurance Holdings at Boston University – a Unique Case Study
Authors: Bernheim B. Douglas , Berstein Solange , Gokhale Jagadeesh , Kotlikoff Laurence J. 
Published: October 2006

This study examines the saving and insurance behaviour of 386 Boston University (BU) employees who volunteered to receive financial planning based on ESPlanner (Economic Security Planner) — a detailed life-cycle financial planning model developed by Economic Security Planning, Inc. Because the employees received their own financial plan, they had a strong incentive to provide full and accurate financial information. Hence, the data appear to be of particularly high quality for studying saving and life insurance decisions.ESPlanner recommends annual levels of consumption, saving, and life insurance holdings that smooth a household's living standard through time subject to the household not exceeding its self-ascribed borrowing limit. The programme treats housing and special expenditures as ‘off-the-top’, adjusts for economies in shared living and the relative costs of raising children, makes highly detailed tax and Social Security benefit calculations, and permits users who don't want a stable living standard to specify how they'd like their living standards to change through time.Our findings are striking. First, the correlation between ESPlanner's saving and insurance prescriptions and the actual decisions being made by BU employees is very weak in the case of saving and essentially zero in the case of life insurance. Many employees are spending far more and saving far less than they should, while others are under-spending and oversaving. The same holds for life insurance. The degree of under-insurance seems particularly acute. Almost 13 per cent of those BU spouses who are secondary earners would experience a 40 per cent or greater drop in their living standards were their spouses to pass away in the near future. Another 13 per cent would experience a 20 to 40 per cent drop. Second, planning shortcomings are as common among high-income professors with significant financial knowledge as they are among low-income staff with limited financial knowledge. Third, two thirds of BU employees are not in a position to smooth their living standards without exceeding their debt limits.
Activities and participation of 9- to 13-year-old children with cerebral palsy
Authors: Voorman Jeanine M , Dallmeijer Annet J , Schuengel Carlo , Knol Dirk L , Lankhorst Gustaaf J , Becher Jules G 
Published: October 2006

Objective: To describe the activities and participation of children with cerebral palsy and to examine the relationship with personal factors and disease characteristics. Design: Cross-sectional study. Setting: Department of Rehabilitation Medicine of a University Medical Center in The Netherlands. Subjects: One hundred and ten children: 70 boys, 40 girls, mean (SD) age 11 years and 3 months (20 months). Outcome measures: Activities and participation, described in the domains of mobility, self-care, domestic life, social life and communication, measured with the Gross Motor Function Measure, the Pediatric Evaluation of Disability Inventory and the Vineland Adaptive Behavior Scales. Results: Multiple linear regression models showed that the Gross Motor Function Classification System (GMFCS) was strongly associated with mobility (explained variance 87-92%), self-care and domestic life. Apart from the GMFCS, cognitive impairment and limb distribution were less important but also significantly associated with self-care and domestic life (explained variance 65-81%). Cognitive impairment and epilepsy were the most important factors associated with social life and communication (explained variance 54-75%). Conclusion: Activities and participation can, to a large extent, be explained by only a few associated factors.
Physical capacity and walking ability after lower limb amputation: a systematic review
Authors: van Velzen J M , van Bennekom C AM , Polomski W , Slootman J R , van der Woude L HV , Houdijk H 
Published: October 2006

Objective: To review the influence of physical capacity on regaining walking ability and the development of walking ability after lower limb amputation. Design: A systematic search of literature was performed. The quality of all relevant studies was evaluated according to a checklist for statistical review of general papers. Subjects: Lower limb amputees. Main measures: Physical capacity (expressed by aerobic capacity, anaerobic capacity, muscle force, flexibility and balance) and walking ability (expressed by the walking velocity and symmetry). Results: A total of 48 studies that complied with the inclusion criteria were selected. From these studies there is strong evidence for deterioration of two aspects of physical capacity (muscle strength and balance) and of two aspects of walking ability (walking velocity and symmetry) after lower limb amputation. Strong evidence was found for a relation between balance and walking ability. Conclusion: Strong evidence was only found for a relation between balance and walking ability. Evidence about a relation between other elements of physical capacity and walking ability was insufficient. Training of physical capacity as well as walking ability during rehabilitation following lower limb amputation should not be discouraged since several parameters have been shown to be reduced after amputation, although their relation to regaining walking ability and to the development of walking ability remains unclear.
The reproducibility and validity of the Canadian Occupational Performance Measure in parents of children with disabilities
Authors: Verkerk Gijs JQ , Wolf Marie Jeanne MAG , Louwers Annoek M , Meester-Delver Anke , Nollet Frans 
Published: October 2006

Objective: To study the reproducibility (inter-rater agreement), the construct and criterion validity of the Canadian Occupational Performance Measure (COPM) in the parents of children with disabilities. Design: The COPM was administered twice by two different occupational therapists. The inter-rater agreement of the content of the prioritized problems was explored. Data analysis of the reproducibility of the scores was based on the Bland and Altman method. Measures used: The construct validity was studied by comparing the results of the COPM with the Pediatric Evaluation of Disability Inventory, and a quality of life questionnaire. The criterion validity was verified with an open-ended question. Setting: Occupational therapy departments of a university hospital and three rehabilitation institutes. Subjects: One hundred and twenty-nine consecutive parents of children referred for occupational therapy. Results: Data were obtained for 80 children with a mean age of 3.7 years (range 1-7.5). Of the prioritized problems identified in the first interview, 80% were also prioritized in the second interview. The limits of agreement were − 2.4 to +2.3 for the mean performance score and − 2.3 to + 2.6 for the mean satisfaction score. Assumptions about the construct and criterion validity were confirmed. Conclusions: The inter-rater agreement of the prioritized problems is good enough for client-centred occupational therapy. The reproducibility of the performance and satisfaction scores is moderate. The results support the construct and criterion validity. The COPM identifies many child-unique problems that are not assessed with existing standardized measurement instruments or with a simple open-ended question.
SSEA-4 identifies mesenchymal stem cells from bone marrow
Authors: Gang Eun J. , Bosnakovski Darko , Figueiredo Camila A. , Visser Jan W. , Perlingeiro Rita C. R. 
Published: October 2006

AbstractAdult bone marrow (BM) contains hematopoietic stem cells (HSCs) as well as a nonhematopoietic, stromal cell population. Within this stromal population are mesenchymal stem cells (MSCs), which not only support hematopoiesis but also differentiate into multiple lineages, including fat, bone, and cartilage. Because of this multipotentiality, the MSC is an attractive candidate for clinical applications to repair or regenerate damaged tissues of mesenchymal origin. However, research progress has been hampered by the limited existing knowledge of the biology of these cells, particularly by the lack of a suitable marker for their prospective isolation. Here, we report that SSEA-4, an early embryonic glycolipid antigen commonly used as a marker for undifferentiated pluripotent human embryonic stem cells and cleavage to blastocyst stage embryos, also identifies the adult mesenchymal stem cell population.
The antiapoptotic protein Mcl-1 is essential for the survival of neutrophils but not macrophages
Authors: Dzhagalov Ivan , St. John Ashley , He You-Wen 
Published: October 2006

AbstractThe antiapoptotic protein Mcl-1, a member of the Bcl-2 family, plays critical roles in promoting the survival of lymphocytes and hematopoietic stem cells. Although previous studies have implicated Mcl-1 in regulating the survival of neutrophils and macrophages, the in vivo function of Mcl-1 in these 2 cell lineages remained unclear. To address this, we have generated mice conditionally lacking Mcl-1 expression in neutrophils and macrophages. We show that Mcl-1 conditional knockout mice had a severe defect in neutrophil survival, whereas macrophage survival was normal. The granulocyte compartment in the blood, spleen, and bone marrow of Mcl-1 conditional knockout mice exhibited an approximately 2- to 3-fold higher apoptotic rate than control cells. In contrast, resting and activated macrophages from Mcl-1–deficient mice exhibited normal survival and contained up-regulated expression of Bcl-2 and Bcl-xL. These data suggest that Mcl-1 plays a nonredundant role in promoting the survival of neutrophils but not macrophages.
The effects of imatinib mesylate treatment before allogeneic transplantation for chronic myeloid leukemia
Authors: Oehler Vivian G. , Gooley Ted , Snyder David S. , Johnston Laura , Lin Allen , Cummings Carrie C. , Chu Su , Bhatia Ravi , Forman Stephen J. , Negrin Robert S. , Appelbaum Frederick R. , Radich Jerald P. 
Published: October 2006

AbstractThe impact of imatinib mesylate (IM) treatment for chronic myeloid leukemia (CML) on subsequent allogeneic transplantation is uncertain. To better understand this relationship, we retrospectively compared 145 patients with CML receiving IM for a minimum of 3 months before allogeneic hematopoietic cell transplantation (HCT) to 231 patients with CML who did not. IM treatment was associated with no increase in early hepatotoxicity or engraftment delay after HCT compared with the historical cohort. In addition, there was no statistically significant difference in the IM-treated cohort compared with the historical cohort with regard to overall survival, disease-free survival, relapse, and nonrelapse mortality. For chronic-phase (CP) patients, IM response prior to HCT was associated with post-HCT outcome. Patients who underwent transplantation in CP with a suboptimal response or a loss of response on IM had a statistically significant higher hazard of mortality when compared with CP patients who achieved a complete cytogenetic response (CCR) or major cytogenetic response (MCR) on IM (HR = 5.31, 95% confidence interval [CI] 1.13-25.05, P = .03). These data indicate that pre-HCT IM is not associated with increased transplant-related morbidity (TRM) or poorer outcomes. However, patients with a suboptimal or loss of IM response before HCT do worse, suggesting a more aggressive disease course for these patients.
Modulation of glutaredoxin in the lung and sputum of cigarette smokers and chronic obstructive pulmonary disease
Authors: Peltoniemi Mirva J , Rytilä Paula H , Harju Terttu H , Soini Ylermi M , Salmenkivi Kaisa M , Ruddock Lloyd W , Kinnula Vuokko L 
Published: October 2006

Abstract

Background
One typical feature in chronic obstructive pulmonary disease (COPD) is the disturbance of the oxidant/antioxidant balance. Glutaredoxins (Grx) are thiol disulfide oxido-reductases with antioxidant capacity and catalytic functions closely associated with glutathione, the major small molecular weight antioxidant of human lung. However, the role of Grxs in smoking related diseases is unclear.

Methods
Immunohistochemical and Western blot analyses were conducted with lung specimens (n = 45 and n = 32, respectively) and induced sputum (n = 50) of healthy non-smokers and smokers without COPD and at different stages of COPD.

Results
Grx1 was expressed mainly in alveolar macrophages. The percentage of Grx1 positive macrophages was significantly lower in GOLD stage IV COPD than in healthy smokers (p = 0.021) and the level of Grx1 in total lung homogenate decreased both in stage I–II (p = 0.045) and stage IV COPD (p = 0.022). The percentage of Grx1 positive macrophages correlated with the lung function parameters (FEV1, r = 0.45, p = 0.008; FEV1%, r = 0.46, p = 0.007, FEV/FVC%, r = 0.55, p = 0.001). Grx1 could also be detected in sputum supernatants, the levels being increased in the supernatants from acute exacerbations of COPD compared to non-smokers (p = 0.013) and smokers (p = 0.051).

Conclusion
The present cross-sectional study showed that Grx1 was expressed mainly in alveolar macrophages, the levels being decreased in COPD patients. In addition, the results also demonstrated the presence of Grx1 in extracellular fluids including sputum supernatants. Overall, the present study suggests that Grx1 is a potential redox modulatory protein regulating the intracellular as well as extracellular homeostasis of glutathionylated proteins and GSH in human lung.
Nuclear envelope transmembrane proteins (NETs) that are up-regulated during myogenesis
Authors: Chen I-Hsiung Brandon , Huber Michael , Guan Tinglu , Bubeck Anja , Gerace Larry 
Published: October 2006

Abstract

Background
The nuclear lamina is a protein meshwork lining the inner nuclear membrane, which contains a polymer of nuclear lamins associated with transmembrane proteins of the inner nuclear membrane. The lamina is involved in nuclear structure, gene expression, and association of the cytoplasmic cytoskeleton with the nucleus. We previously identified a group of 67 novel putative nuclear envelope transmembrane proteins (NETs) in a large-scale proteomics analysis. Because mutations in lamina proteins have been linked to several human diseases affecting skeletal muscle, we examined NET expression during differentiation of C2C12 myoblasts. Our goal was to identify new nuclear envelope and lamina components whose expression is coordinated with muscle differentiation.

Results
Using transcriptional microarray analysis, we found that expression of 6 of the NETs significantly increases during myoblast differentiation. We confirmed these results using quantitative RT-PCR, and furthermore, found that all 6 NETs are expressed at high levels in adult mouse skeletal muscle relative to 9 other tissues examined. Using epitope-tagged cDNAs, we determined that the 5 NETs we could analyze (NETs 9, 25, 32, 37 and 39) all target to the nuclear envelope in C2C12 cells. Furthermore, the 3 NETs that we could analyze by immunoblotting were highly enriched in nuclear envelopes relative to microsomal membranes purified from mouse liver. Database searches showed that 4 of the 6 up-regulated NETs contain regions of homology to proteins previously linked to signaling.

Conclusion
This work identified 6 NETs that are predicted to have important functions in muscle development and/or maintenance from their expression patterns during myoblast differentiation and in mouse tissues. We confirmed that 5 of these NETs are authentic nuclear envelope proteins. Four members of this group have potential signaling functions at the NE, based on their sequence homologies.
Functional role of aspartic proteinase cathepsin D in insect metamorphosis
Authors: Gui Zhong Zheng , Lee Kwang Sik , Kim Bo Yeon , Choi Yong Soo , Wei Ya Dong , Choo Young Moo , Kang Pil Don , Yoon Hyung Joo , Kim Iksoo , Je Yeon Ho , Seo Sook Jae , Lee Sang Mong , Guo Xijie , Sohn Hung Dae , Jin Byung Rae 
Published: October 2006

Abstract

Background
Metamorphosis is a complex, highly conserved and strictly regulated development process that involves the programmed cell death of obsolete larval organs. Here we show a novel functional role for the aspartic proteinase cathepsin D during insect metamorphosis.

Results
Cathepsin D of the silkworm Bombyx mori (BmCatD) was ecdysone-induced, differentially and spatially expressed in the larval fat body of the final instar and in the larval gut of pupal stage, and its expression led to programmed cell death. Furthermore, BmCatD was highly induced in the fat body of baculovirus-infected B. mori larvae, suggesting that this gene is involved in the induction of metamorphosis of host insects infected with baculovirus. RNA interference (RNAi)-mediated BmCatD knock-down inhibited programmed cell death of the larval fat body, resulting in the arrest of larval-pupal transformation. BmCatD RNAi also inhibited the programmed cell death of larval gut during pupal stage.

Conclusion
Based on these results, we concluded that BmCatD is critically involved in the programmed cell death of the larval fat body and larval gut in silkworm metamorphosis.