bluuebunny/crossref_metadata_2025_split huggingface dataset:
Red-cell ICAM-4 is a ligand for the monocyte/macrophage integrin CD11c/CD18: characterization of the binding sites on ICAM-4
Authors: Ihanus Eveliina , Uotila Liisa M. , Toivanen Anne , Varis Minna , Gahmberg Carl G. 
Published: September 2006

AbstractIntercellular adhesion molecule 4 (ICAM-4) is a unique member of the ICAM family because of its specific expression on erythroid cells and ability to interact with several types of integrins expressed on blood and endothelial cells. The first reported receptors for ICAM-4 were CD11a/CD18 and CD11b/CD18. In contrast to these 2, the cellular ligands and the functional role of the third β2 integrin, CD11c/CD18, have not been well defined. Here, we show that ICAM-4 functions as a ligand for the monocyte/macrophage-specific CD11c/CD18. Deletion of the individual immunoglobulin domains of ICAM-4 demonstrated that both its domains contain binding sites for CD11c/CD18. Analysis of a panel of ICAM-4 point mutants identified residues that affected binding to the integrin. By molecular modeling the important residues were predicted to cluster in 2 distinct but spatially close regions of the first domain with an extension to the second domain spatially distant from the other residues. We also identified 2 peptides derived from sequences of ICAM-4 that are capable of modulating the binding to CD11c/CD18. CD11c/CD18 is expressed on macrophages in spleen and bone marrow. Inhibition of erythrophagocytosis by anti–ICAM-4 and anti-integrin antibodies suggests a role for these interactions in removal of senescent red cells.
Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD)
Authors: Goodeve Anne , Eikenboom Jeroen , Castaman Giancarlo , Rodeghiero Francesco , Federici Augusto B. , Batlle Javier , Meyer Dominique , Mazurier Claudine , Goudemand Jenny , Schneppenheim Reinhard , Budde Ulrich , Ingerslev Jorgen , Habart David , Vorlova Zdena , Holmberg Lars , Lethagen Stefan , Pasi John , Hill Frank , Soteh Mohammad Hashemi , Baronciani Luciano , Hallden Christer , Guilliatt Andrea , Lester Will , Peake Ian 
Published: September 2006

AbstractType 1 von Willebrand disease (VWD) is characterized by a personal and family history of bleeding coincident with reduced levels of normal plasma von Willebrand factor (VWF). The molecular basis of the disorder is poorly understood. The aims of this study were to determine phenotype and genotype and their relationship in patients historically diagnosed with type 1 VWD. Families were recruited in 9 European countries based on previous type 1 VWD diagnosis. Bleeding symptoms were recorded, plasma phenotype analyzed, and VWF mutation analysis performed in all index cases (ICs). Phenotypic and molecular analysis stratified patients into those with or without phenotypes suggestive of qualitative VWF defects (abnormal multimers) and with or without mutations. A total of 105 of 150 ICs (70%) had mutations identified. A subgroup with abnormal multimers (38% of ICs, 57 of 150) showed a high prevalence of VWF gene mutations (95% of ICs, 54 of 57), whereas in those with qualitatively normal VWF, fewer mutations were identified (55% of ICs, 51 of 93). About one third of the type 1 VWD cases recruited could be reconsidered as type 2. The remaining group could be considered “true” type 1 VWD, although mutations were found in only 55%.
Human mesenchymal stem cells isolated from bone marrow and lymphoid organs support tumor B-cell growth: role of stromal cells in follicular lymphoma pathogenesis
Authors: Amé-Thomas Patricia , Maby-El Hajjami Hélène , Monvoisin Céline , Jean Rachel , Monnier Delphine , Caulet-Maugendre Sylvie , Guillaudeux Thierry , Lamy Thierry , Fest Thierry , Tarte Karin 
Published: September 2006

AbstractAccumulating evidence indicates that the cellular microenvironment plays a key role in follicular lymphoma (FL) pathogenesis, both within tumor lymph nodes (LNs) and in infiltrated bone marrow where ectopic LN-like reticular cells are integrated within malignant B-cell nodular aggregates. In normal secondary lymphoid organs, specific stromal cell subsets provide a highly specialized microenvironment that supports immune response. In particular, fibroblastic reticular cells (FRCs) mediate immune cell migration, adhesion, and reciprocal interactions. The role of FRCs and their postulated progenitors, that is, bone marrow mesenchymal stem cells (MSCs), in FL remains unexplored. In this study, we investigated the relationships between FRCs and MSCs and their capacity to sustain malignant B-cell growth. Our findings strongly suggest that secondary lymphoid organs contain MSCs able to give rise to adipocytes, chondrocytes, osteoblasts, as well as fully functional B-cell supportive FRCs. In vitro, bone marrow–derived MSCs acquire a complete FRC phenotype in response to a combination of tumor necrosis factor-α and lymphotoxin-α1β2. Moreover, MSCs recruit primary FL cells that, in turn, trigger their differentiation into FRCs, making them able to support malignant B-cell survival. Altogether, these new insights into the cross talk between lymphoma cells and their microenvironment could offer original therapeutic strategies.
End expiratory oxygen concentrations to predict central venous oxygen saturation: an observational pilot study
Authors: Jones Alan E , Kuehne Karl , Steuerwald Michael , Kline Jeffrey A 
Published: September 2006

Abstract

Background
A non-invasive surrogate measurement for central venous oxygen saturation (ScVO2) would be useful in the ED for assessing therapeutic interventions in critically ill patients. We hypothesized that either linear or nonlinear mathematical manipulation of the partial pressure of oxygen in breath at end expiration (EtO2) would accurately predict ScVO2.

Methods
Prospective observational study of a convenience sample of hemodialysis patients age > 17 years with existing upper extremity central venous catheters were enrolled. Using a portable respiratory device, we collected both tidal breathing and end expiratory oxygen and carbon dioxide concentrations, volume and flow on each patient. Simultaneous ScVO2 measurements were obtained via blood samples collected from the hemodialysis catheter. Two models were used to predict ScVO2: 1) Best-fit multivariate linear regression equation incorporating all respiratory variables; 2) MathCAD to model the decay curve of EtO2 versus expiratory volume using the least squares method to estimate the pO2 that would occur at <20% of total lung capacity.

Results
From 21 patients, the correlation between EtO2 and measured ScVO2 yielded R2 = 0.11. The best fit multivariate equation included EtCO2 and EtO2 and when solved for ScVO2, the equation yielded a mean absolute difference from the measured ScVO2 of 8 ± 6% (range -18 to +17%). The predicted ScVO2 value was within 10% of the actual value for 57% of the patients. Modeling of the EtO2 curve did not accurately predict ScVO2 at any lung volume.

Conclusion
We found no significant correlation between EtO2 and ScVO2. A linear equation incorporating EtCO2 and EtO2 had at best modest predictive accuracy for ScVO2.
RB acute loss induces centrosome amplification and aneuploidy in murine primary fibroblasts
Authors: Iovino Flora , Lentini Laura , Amato Angela , Di Leonardo Aldo 
Published: September 2006

AbstractBackgroundIncorrect segregation of whole chromosomes or parts of chromosome leads to aneuploidy commonly observed in cancer. The correct centrosome duplication, assuring assembly of a bipolar mitotic spindle, is essential for chromosome segregation fidelity and preventing aneuploidy. Alteration of p53 and pRb functions by expression of HPV16-E6 and E7 oncoproteins has been associated with centrosome amplification. However, these last findings could be the result of targeting cellular proteins in addition to pRb by HPV16-E7 oncoprotein. To get a more detailed picture on the role of pRb in chromosomal instability and centrosome amplification, we analyzed the effects of the acute loss of retinoblastoma gene function in primary conditionalRbdeficient mouse embryonic fibroblasts (MEFs). Moreover, since pRb is a transcriptional repressor, microarray analysis was done on pRb-competent and pRb-deficient MEFs to evaluate changes in expression of genes for centrosome homeostasis and for correct mitosis.ResultsAcute loss of pRb induces centrosome amplification and aneuploidy in the vast majority of cells analyzed. A time course analysis shows a decrease of cells with amplified centrosomes after 40 days from the adenoviral infection. At this time only 12% of cells still show amplified centrosomes. Interestingly, cells with pRb constitutive loss show a similar percentage of cells with amplified centrosomes. DNA-Chip analyses in MEFs wt (mock infected) and pRb depleted (Ad-Cre infected) cells reveal differential expression of genes controlling both centrosome duplication and mitotic progression.ConclusionOur findings suggest a direct link between pRb status, centrosome amplification and chromosomal instability, and define specific mitotic genes as targets whose gene expression has to be altered to achieve or maintain aneuploidy.
Collision tumor of the thyroid: follicular variant of papillary carcinoma and squamous carcinoma
Authors: Walvekar Rohan R , Kane Subhadra V , D'Cruz Anil K 
Published: September 2006

Abstract

Background
Collision tumors of the thyroid gland are a rare entity. We present a case of a follicular variant of papillary carcinoma and squamous carcinoma in the thyroid. To the best of our knowledge, this is the first documentation of a collision tumor with a papillary carcinoma and a squamous carcinoma within the thyroid gland. The clinicopathological features and immunohistochemical profile are reported. The theories of origin, epidemiology and management are discussed with a literature review.

Case presentation
A 65 year old woman presented with a large thyroid swelling of 10 years duration and with swellings on the back and scalp which were diagnosed to be a follicular variant of papillary thyroid carcinoma with metastasis. Clinical examination, radiology and endoscopy ruled out any other abnormality of the upper aerodigestive tract. The patient was treated surgically with a total thyroidectomy with central compartment clearance and bilateral selective neck dissections. The histopathology revealed a collision tumor with components of both a follicular variant of papillary carcinoma and a squamous carcinoma. Immunohistochemical analysis confirmed the independent origin of these two primary tumors. Adjuvant radio iodine therapy directed toward the follicular derived component of the thyroid tumor and external beam radiotherapy for the squamous component was planned.

Conclusion
Collision tumors of the thyroid gland pose a diagnostic as well as therapeutic challenge. Metastasis from distant organs and contiguous primary tumors should be excluded. The origins of squamous cancer in the thyroid gland must be established to support the true evolution of a collision tumor and to plan treatment. Treatment for collision tumors depends upon the combination of primary tumors involved and each component of the combination should be treated like an independent primary. The reporting of similar cases with longer follow-up will help define the epidemiology, biology and establish standardized protocols for treatment of these extremely rare tumors.
Disease-modifying antirheumatic drugs are associated with a reduced risk for cardiovascular disease in patients with rheumatoid arthritis: a case control study
Authors: van Halm Vokko P , Nurmohamed Michael T , Twisk Jos WR , Dijkmans Ben AC , Voskuyl Alexandre E 
Published: September 2006

AbstractRheumatoid arthritis (RA) is characterized by inflammation and an increased risk for cardiovascular disease (CVD). This study investigates possible associations between CVD and the use of conventional disease-modifying antirheumatic drugs (DMARDs) in RA. Using a case control design, 613 RA patients (5,649 patient-years) were studied, 72 with CVD and 541 without CVD. Data on RA, CVD and drug treatment were evaluated from time of RA diagnosis up to the first cardiovascular event or the end of the follow-up period. The dataset was categorized according to DMARD use: sulfasalazine (SSZ), hydroxychloroquine (HCQ) or methotrexate (MTX). Odds ratios (ORs) for CVD, corrected for age, gender, smoking and RA duration, were calculated per DMARD group. Patients who never used SSZ, HCQ or MTX were used as a reference group. MTX treatment was associated with a significant CVD risk reduction, with ORs (95% CI): 'MTX only', 0.16 (0.04 to 0.66); 'MTX and SSZ ever', 0.20 (0.08 to 0.51); and 'MTX, SSZ and HCQ ever', 0.20 (0.08 to 0.54). The risk reductions remained significant after additional correction for the presence of rheumatoid factor and erosions. After correction for hypertension, diabetes and hypercholesterolemia, 'MTX or SSZ ever' and 'MTX, SSZ and HCQ ever' showed significant CVD risk reduction. Rheumatoid factor positivity and erosions both increased CVD risk, with ORs of 2.04 (1.02 to 4.07) and 2.36 (0.92 to 6.08), respectively. MTX and, to a lesser extent, SSZ were associated with significantly lower CVD risk compared to RA patients who never used SSZ, HCQ or MTX. We hypothesize that DMARD use, in particular MTX use, results in powerful suppression of inflammation, thereby reducing the development of atherosclerosis and subsequently clinically overt CVD.
Expression and Localization of δ-, κ-, and μ-Opioid Receptors in Human Spermatozoa and Implications for Sperm Motility
Authors: Agirregoitia Ekaitz , Valdivia Asier , Carracedo Arkaitz , Casis Luis , Gil Javier , Subiran Nerea , Ochoa Carmen , Irazusta Jon 
Published: September 2006

Abstract
Context: Endogenous opioid peptides signal through δ-, κ-, and μ-opioid receptors. Some of these peptides such as endorphins and enkephalins are present in the male reproductive tract, but the presence of the corresponding receptors in human sperm cells has not yet been reported.
Objective: Our objective was to study the expression and localization of δ-, κ-, and μ-opioid receptors on human spermatozoa and the implication in sperm motility.
Methods: The expression of receptors was studied by RT-PCR, Western blot, and immunofluorescence techniques. We evaluated the effects of activation of each opioid receptor by specific agonist and antagonist.
Results: Human spermatozoa express δ-, κ-, and μ-opioid receptors. These receptors were located in different parts of the head, in the middle region, and in the tail of the sperm. Progressive motility of spermatozoa, an important parameter to evaluate male fertility, was found to be significantly reduced after incubation with the μ-receptor agonist morphine, whereas this effect was antagonized in the presence of the corresponding antagonist naloxone. The δ-receptor antagonist naltrindole significantly reduced progressive motility immediately after its addition. However, the δ-receptor agonist DPDPE had no significant effect. Finally, neither the κ-receptor agonist U50488 nor its antagonist nor-binaltorphimine significantly affected the progressive motility of human spermatozoa.
Conclusion: We report for first time the presence of functional δ-, κ-, and μ-opioid receptors in human sperm membranes. These findings are indicative of a role for the opioid system in the regulation of sperm physiology.
β-Adrenergic and Atrial Natriuretic Peptide Interactions on Human Cardiovascular and Metabolic Regulation
Authors: Birkenfeld Andreas L. , Boschmann Michael , Moro Cedric , Adams Frauke , Heusser Karsten , Tank Jens , Diedrich André , Schroeder Christoph , Franke Gabi , Berlan Michel , Luft Friedrich C. , Lafontan Max , Jordan Jens 
Published: September 2006

AbstractContext: Atrial natriuretic peptide (ANP) has well-known cardiovascular effects and modifies lipid and carbohydrate metabolism in humans.Objective: The objective of the study was to determine the metabolic and cardiovascular interaction of β-adrenergic receptors and ANP.Design: This was a crossover study, conducted 2004–2005.Setting: The study was conducted at an academic clinical research center.Patients: Patients included 10 healthy young male subjects (body mass index 24 ± 1 kg/m2).Intervention: We infused iv incremental ANP doses (6.25, 12.5, and 25 ng/kg·min) with and without propranolol (0.20 mg/kg in divided doses followed by 0.033 mg/kg·h infusion). Metabolism was monitored through venous blood sampling, im, and sc microdialysis and indirect calorimetry. Cardiovascular changes were monitored by continuous electrocardiogram and beat-by-beat blood pressure recordings.Main Outcome Measures: Venous nonesterified fatty acid, glycerol, glucose, and insulin; and microdialysate glucose, glycerol, lactate, and pyruvate were measured.Results: ANP increased heart rate dose dependently. β-Adrenergic receptor blockade abolished the response. ANP elicited a dose-dependent increase in serum nonesterified fatty acid and glycerol concentrations. The response was not suppressed with propranolol. Venous glucose and insulin concentrations increased with ANP, both without or with propranolol. ANP induced lipid mobilization in sc adipose tissue. In skeletal muscle, microdialysate lactate increased, whereas the lactate to pyruvate ratio decreased, both with and without propranolol. Higher ANP doses increased lipid oxidation, whereas energy expenditure remained unchanged. Propranolol tended to attenuate the increase in lipid oxidation.Conclusions: Selected cardiovascular ANP effects are at least partly mediated by β-adrenergic receptor stimulation. ANP-induced changes in lipid mobilization and glycolysis are mediated by another mechanism, presumably stimulation of natriuretic peptide receptors, whereas substrate oxidation might be modulated through adrenergic mechanisms.
Spontaneous Hypothyroidism in Adult Women Is Predicted by Small Body Size at Birth and during Childhood
Authors: Kajantie Eero , Phillips David I. W. , Osmond Clive , Barker David J. P. , Forsén Tom , Eriksson Johan G. 
Published: September 2006

Abstract
Background: The relationships of early growth with coronary heart disease and type 2 diabetes have received considerable attention. It is not known whether fetal or childhood growth is linked with autoimmune disorders.
Objective: Our objective was to assess whether the risk of adult-onset spontaneous hypothyroidism is predicted by body size at birth and during childhood.
Design and Setting: We conducted a birth cohort study in Helsinki, Finland.
Participants: A total of 293 women who were born between 1934 and 1944 and had their heights and weights recorded at birth and during childhood participated in the study.
Measurements: We measured spontaneous hypothyroidism, defined as: 1) a disease history confirmed from medical records, or 2) previously undiagnosed hypothyroidism (TSH &gt; 10 mU/liter).
Results: Twenty women (6.8%) had spontaneous hypothyroidism; 18 had been diagnosed previously, between 43 and 65 yr of age, and two had undiagnosed subclinical hypothyroidism. In addition, 59 women were thyroid peroxidase antibody positive. Compared with the 214 thyroid peroxidase antibody-negative women with no thyroid disorder, those with spontaneous hypothyroidism had on average 252 g [95% confidence interval (CI), 61 to 443 g; P = 0.01] lower birth weight and 1.2 cm (95% CI, 0.5 to 2.0 cm; P = 0.002) shorter length at birth. The odds of developing hypothyroidism increased 4.4-fold per kilogram decrease in birth weight (95% CI, 1.4 to 14.1). Hypothyroid subjects had been shorter in early childhood and had lower body mass index during later childhood.
Conclusions: Small body size at birth and during childhood increases the risk of spontaneous hypothyroidism in adult women.
Impact of Type 2 Diabetes on Myocardial Insulin Sensitivity to Glucose Uptake and Perfusion in Patients with Coronary Artery Disease
Authors: Søndergaard Hanne M. , Bøttcher Morten , Marie Madsen Mette , Schmitz Ole , Hansen Søren B. , Nielsen Torsten T. , Bøtker Hans Erik 
Published: September 2006

Abstract
Background and Hypothesis: Myocardial insulin resistance (IR) is a feature of coronary artery disease (CAD) with reduced left ventricular ejection fraction (LVEF). Whether type 2 diabetes mellitus (T2DM) with CAD and preserved LVEF induces myocardial IR and whether insulin in these patients acts as a myocardial vasodilator is debated.
Methods: We studied 27 CAD patients (LVEF &gt; 50%): 12 with T2DM (CAD+DM), 15 without T2DM (CAD-NoDM). Regional myocardial and skeletal glucose uptake, myocardial and skeletal muscle perfusion were measured with positron emission tomography. Myocardial muscle perfusion was measured at rest and during hyperemia in nonstenotic and stenotic regions with and without acute hyperinsulinemia.
Results: Myocardial glucose uptake was similar in CAD+DM and CAD-NoDM in both nonstenotic and stenotic regions [0.38 ± 0.08 and 0.36 ± 0.11 μmol/g·min; P value nonsignificant (NS)] and (0.35 ± 0.09 and 0.37 ± 0.13 μmol/g·min; P = NS). Skeletal glucose uptake was reduced in CAD+DM (0.05 ± 0.04 vs. 0.10 ± 0.05 μmol/g·min; P = 0.02), and likewise, whole-body glucose uptake was reduced in CAD+DM (4.0 ± 2.8 vs. 7.0 ± 2.4 mg/kg·min; P = 0.01). Insulin did not alter myocardial muscle perfusion at rest or during hyperemia. Insulin increased skeletal muscle perfusion in CAD-NoDM (0.11 ± 0.03 vs. 0.06 ± 0.03 ml/g·min; P = 0.02), but not in CAD+DM (0.08 ± 0.04 and 0.09 ± 0.05 ml/g·min; P = NS).
Conclusion: Myocardial IR to glucose uptake is not an inherent feature in T2DM patients with preserved LVEF. Acute physiological insulin exposure exerts no coronary vasodilation in CAD patients irrespective of T2DM.
Cladribine: An Investigational Immunomodulatory Agent for Multiple Sclerosis
Authors: Brousil Julie A , Roberts Russel J , Schlein Amanda L 
Published: September 2006

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of cladribine, a purine analog undergoing Phase III trials for approval of its use in the treatment of multiple sclerosis (MS). Data Sources: A MEDLINE search (1966–September 2006) was conducted using the key words cladribine and multiple sclerosis. No limits were placed on the search. Study Selection and Data Extraction: Studies and review articles related to cladribine and MS were reviewed. The trials examining the role of cladribine in MS were analyzed. Data Synthesis: Cladribine is a purine analog that demonstrates lymphocytotoxic activity. Recent data suggest that cladribine may have a role in the treatment of relapsing–remitting and the progressive forms of MS. In these studies, cladribine has shown mixed results in decreasing neurologic disability, as measured by various rating scales, but has consistently shown positive results in reducing the number of enhancing lesions, which reflects a measure of disease activity. To date, there is one ongoing study examining the role of oral cladribine in the treatment of relapsing–remitting MS. The incidence of adverse effects with cladribine has been significantly greater than with placebo, with the most common being myelosuppression. Conclusions: While data do not support its use as a first-line MS treatment, cladribine may be a promising agent for refractory patients with secondary progressive MS. Further studies are warranted.