Innate immune functions of macrophage subpopulations in the spleen.

In the different compartments of the spleen, macrophage populations can be found that have different functions depending on their localization. In the lymphoid compartment of the spleen, the white pulp, macrophages are in essence similar to populations found in lymph nodes and other organized secondary lymphoid organs. In the red pulp, large populations of classical scavenger macrophages are found that, in addition to scavenging blood-borne debris, are involved in iron recycling by phagocytosis of effete red blood cells.

Biomarker analysis in a phase III study of pemetrexed-carboplatin versus etoposide-carboplatin in chemonaive patients with extensive-stage small-cell lung cancer.

Background: Clinical results of a randomized phase III trial comparing pemetrexed-carboplatin (PC) with etoposide-carboplatin (EC) in chemonaive patients with extensive-stage disease small-cell lung cancer (ED-SCLC) resulted in trial closure for futility; biomarker analyses using immunohistochemistry (IHC) and single-nucleotide polymorphisms (SNPs) are described herein.

Patients And Methods: Thymidylate synthase (TS), excision repair cross complementing-1 (ERCC1), glycinamide ribonucleotide formyltransferase (GARFT), and folylpolyglutamate synthetase (FPGS) were investigated using IHC (n=395). SNPs were genotyped for TS, FPGS, γ-glutamyl hydrolase (GGH), methylenetetrahydrofolate reductase (MTHFR), folate receptor-α FR-α, and solute carrier 19A1 (SLC19A1; n=611).

Valsartan improves {beta}-cell function and insulin sensitivity in subjects with impaired glucose metabolism: a randomized controlled trial.

Objective: Recently, the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research Trial demonstrated that treatment with the angiotensin receptor blocker (ARB) valsartan for 5 years resulted in a relative reduction of 14% in the incidence of type 2 diabetes in subjects with impaired glucose metabolism (IGM). We investigated whether improvements in β-cell function and/or insulin sensitivity underlie these preventive effects of the ARB valsartan in the onset of type 2 diabetes.

Research Design And Methods: In this randomized controlled, double-blind, two-center study, the effects of 26 weeks of valsartan (320 mg daily; n = 40) or placebo (n = 39) on β-cell function and insulin sensitivity were assessed in subjects with impaired fasting glucose and/or impaired glucose tolerance, using a combined hyperinsulinemic-euglycemic and hyperglycemic clamp with subsequent arginine stimulation and a 2-h 75-g oral glucose tolerance test (OGTT).

Expression of retinaldehyde dehydrogenase enzymes in mucosal dendritic cells and gut-draining lymph node stromal cells is controlled by dietary vitamin A.

The vitamin A metabolite retinoic acid (RA) plays a crucial role in mucosal immune responses. We demonstrate in this study that RA-producing retinaldehyde dehydrogenase (RALDH) enzymes are postnatally induced in mesenteric lymph node (MLN) dendritic cells (DCs) and MLN stromal cells. RALDH enzyme activity in lamina propria-derived CD103(+) MLN-DCs did not depend on TLR signaling.

Magnetic resonance imaging predictors of conversion to multiple sclerosis in the BENEFIT study.

Background: Several studies have confirmed the predictive value of baseline and follow-up magnetic resonance (MR) imaging variables for conversion to clinically definite multiple sclerosis (CDMS), depending on the population, follow-up duration, and treatment intervention. However, the timing of follow-up imaging and the effect of treatment intervention on the predictive value of baseline MR imaging variables require further elucidation.

Objectives: To assess the prognostic value of baseline MR imaging variables for conversion to CDMS over 3 years and whether this was affected by treatment intervention and (2) to assess the increased risk for conversion posed by dissemination in time on follow-up MR imaging.

TLR triggering on tolerogenic dendritic cells results in TLR2 up-regulation and a reduced proinflammatory immune program.

Tolerogenic dendritic cells (TDC) offer a promising therapeutic potential to ameliorate autoimmune diseases. Reported to inhibit adaptive immune responses, little is known about their innate immunity receptor repertoire. In this study, we compared three types of human TDC (IL-10-DC, dexamethasone (DX)-DC, and 1,25(OH)(2)D(3)-DC) by their TLR expression and response to a set of TLR ligands.

A multiple testing approach to high-dimensional association studies with an application to the detection of associations between risk factors of heart disease and genetic polymorphisms.

We present an approach to association studies involving a dozen or so ;response' variables and a few hundred ;explanatory' variables which emphasizes transparency, simplicity, and protection against spurious results. The methods proposed are largely non-parametric, and they are systematically rounded-off by the Benjamini-Hochberg method of multiple testing. An application to the detection of associations between risk factors of heart disease and genetic polymorphisms using the REGRESS dataset provides ample illustration of our approach.

Outcomes of stereotactic radiotherapy for a new clinical stage I lung cancer arising postpneumonectomy.

Background: Resection of second primary lung tumors that arise after previous pneumonectomy is associated with a high risk of complications. In this study, the authors reviewed outcomes after stereotactic radiation therapy (SRT) for such patients.

Methods: SRT was undergone by 15 patients who developed a new clinical stage I lung cancer at a median of 8.

Global similarity with local differences in linkage disequilibrium between the Dutch and HapMap-CEU populations.

The HapMap project has facilitated the selection of tagging single nucleotide polymorphisms (tagSNPs) for genome-wide association studies (GWAS) under the assumption that linkage disequilibrium (LD) in the HapMap populations is similar to the populations under investigation. Earlier reports support this assumption, although in most of these studies only a few loci were evaluated. We compared pair-wise LD and LD block structure across autosomes between the Dutch population and the CEU-HapMap reference panel.

Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-kappaB activation through Raf-1 and Syk.

The C-type lectin dectin-1 activates the transcription factor NF-kappaB through a Syk kinase-dependent signaling pathway to induce antifungal immunity. Here we show that dectin-1 expressed on human dendritic cells activates not only the Syk-dependent canonical NF-kappaB subunits p65 and c-Rel, but also the noncanonical NF-kappaB subunit RelB. Dectin-1, when stimulated by the beta-glucan curdlan or by Candida albicans, induced a second signaling pathway mediated by the serine-threonine kinase Raf-1, which integrated with the Syk pathway at the point of NF-kappaB activation.

Parental experiences of childhood leukemia treatment in indonesia.

In our study, we examined socioeconomic, treatment-related, and psychologic experiences of parents during the acute lymphoblastic leukemia treatment of their children in an academic hospital in Indonesia. Children were treated with the WK-ALL-2000 protocol and received donated chemotherapy. From November 2004 to April 2006, 51 parents were interviewed by psychologists using semi-structured questionnaires.

Contacts between medial and lateral perforant pathway fibers and parvalbumin expressing neurons in the subiculum of the rat.

The entorhinal cortex (EC) projects via the perforant pathway to all subfields in the hippocampal formation. One can distinguish medial and lateral components in the pathway, originating in corresponding medial and lateral subdivisions of EC. We analyzed the innervation by medial and lateral perforant pathway fibers of parvalbumin-expressing neurons in the subiculum.

Pronating radius osteotomy for supination deformity in children with obstetric brachial plexus palsy.

Purpose: In obstetric brachial plexus lesions, muscle imbalance caused by active supinator muscles and paralyzed pronator muscles can result in a supination position of the wrist, which, apart from cosmesis, may interfere with function.

Methods: In this retrospective study, we describe the results of a pronating radius osteotomy for supination deformity of the hand in children with an obstetric brachial plexus lesion.

Results: After a mean follow-up of 23 months, all 8 patients (mean age, 9.

Loss of thalamic serotonin transporters in early drug-naïve Parkinson's disease patients is associated with tremor: an [(123)I]beta-CIT SPECT study.

In vitro studies revealed serotonin transporter (5-HTT) decline in Parkinson's disease (PD). Yet, few studies investigated thalamic 5-HTT in vivo and its effect on PD heterogeneity. We analyzed thalamic [(123)I]beta-CIT binding (mainly reflecting 5-HTT binding) in 32 drug-naïve PD patients and 13 controls with SPECT.

Unsuspected chronic traumatic aortic pseudoaneurysm--what to do about it. Late post-traumatic aortic pseudoaneurysm.

A 59-year-old man with multiple risk factors for coronary artery disease who had been in a motor vehicle accident 30 years earlier presented with new-onset angina pectoris. During cardiac catheterization, an ill-defined dense area was noted in the mediastinum. Chest radiography showed an area of calcification around the proximal descending aorta.

The new peritoneal dialysis solutions: friends only, or foes in part?

Over the past decade new solutions for peritoneal dialysis have been developed in an effort to reduce the bioincompatibility of conventional glucose-containing, lactate-buffered solutions, and thereby to improve the clinical outcomes of peritoneal dialysis. The new solutions contain either other non-glucose osmotic agents, such as glucose polymers or amino acids, or have a neutral pH; the buffer content is altered in some of the new solutions. In vitro and in vivo studies have shown the biocompatibility of these new solutions to be superior to that of standard solutions.

Attitude of health-care providers toward childhood leukemia patients with different socio-economic status.

Background: Treatment results differ significantly between poor and prosperous children with leukemia in Indonesia. The objective of this study was to determine whether parental socio-economic status influences beliefs, attitude, and behavior of health-care providers (hcp) treating childhood leukemia in Indonesia.

Procedure: A self-administered semi-structured questionnaire was filled in by 102 hcp (69 doctors, 28 nurses, 2 psychologists, 2 hematology technicians, 1 administrator).

A method to provide integrated care for complex medically ill patients: the INTERMED.

A growing number of nursing subspecializations have been developed in recent decades. Topics of concern are that care is not tailored to cope with the growing number of patients with more than one chronic disease, there is an increase in co-ordination problems in the care that is provided for this group of complex patients, and the care for these complex patients is extremely fragmented. The assessment of health risks resulting in co-ordinated care with effective communication is vital for multimorbid patients.

Fasting and postprandial glycoxidative and lipoxidative stress are increased in women with type 2 diabetes.

Objective: We studied acute changes in markers of glycoxidative and lipoxidative stress, including oxidized LDL, N(epsilon)-(carboxyethyl)-lysine (CEL), N(epsilon)-(carboxymethyl)-lysine (CML), and 3-deoxyglucosone (3DG), following two consecutive meals.

Research Design And Methods: Postmenopausal women (27 with normal glucose metabolism [NGM], 26 with type 2 diabetes) received two consecutive fat-rich meals and two consecutive carbohydrate-rich meals on two occasions. Glucose and triglyceride concentrations were measured at baseline and 1, 2, 4, 6, and 8 h following breakfast; lunch was given at 4 h.

Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation.

Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) has recently been defined based on a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy. LBSL is an autosomal recessive disease, most often manifesting in early childhood. Affected individuals develop slowly progressive cerebellar ataxia, spasticity and dorsal column dysfunction, sometimes with a mild cognitive deficit or decline.

Influence of socioeconomic status on childhood acute lymphoblastic leukemia treatment in Indonesia.

Objective: A major reason for poor survival of childhood acute lymphoblastic leukemia in developing countries is treatment refusal or abandonment. This can be associated with parental socioeconomic status and attitudes of health care providers. Our study examined the influence of 2 socioeconomic status determinants, parental income and education, on treatment in an Indonesian academic hospital.

Regulation of effector T cells by antigen-presenting cells via interaction of the C-type lectin MGL with CD45.

Homeostatic control of T cells involves tight regulation of effector T cells to prevent excessive activation that can cause tissue damage and autoimmunity. Little is known, however, about whether antigen-presenting cells (APCs) are also involved in maintaining immune system homeostasis once effector T cells are stimulated. Here we found that immature APCs downregulated effector T cell function by a mechanism involving the C-type lectin MGL expressed by APCs.

Factors determining early pregnancy loss in singleton and multiple implantations.

Background: The incidence of first trimester pregnancy loss is much lower in IVF twin pregnancies than in IVF singleton pregnancies. The objective of this study was to determine which embryonic and maternal factors contribute to this finding.

Methods: Retrospective data analysis of the outcome of 1593 pregnancies after day 3 double-embryo transfer (DET) after IVF or ICSI treatment.