Vimentin deficiency in macrophages induces increased oxidative stress and vascular inflammation but attenuates atherosclerosis in mice.

The aim was to clarify the role of vimentin, an intermediate filament protein abundantly expressed in activated macrophages and foam cells, in macrophages during atherogenesis. Global gene expression, lipid uptake, ROS, and inflammation were analyzed in bone-marrow derived macrophages from vimentin-deficient (Vim) and wild-type (Vim) mice. Atherosclerosis was induced in Ldlr mice transplanted with Vim and Vim bone marrow, and in Vim and Vim mice injected with a PCSK9 gain-of-function virus.

Microdialysis and proteomics of subcutaneous interstitial fluid reveals increased galectin-1 in type 2 diabetes patients.

Objective: To identify a potential therapeutic target for type 2 diabetes by comparing the subcutaneous interstitial fluid from type 2 diabetes patients and healthy men.

Methods: Proteomics was performed on the interstitial fluid of subcutaneous adipose tissue obtained by microdialysis from 7 type 2 diabetes patients and 8 healthy participants. 851 proteins were detected, of which 36 (including galectin-1) showed significantly altered expression in type 2 diabetes.

Hypoxia-induced regulation of the very low density lipoprotein receptor.

The very low density lipoprotein receptor (VLDLr) is highly upregulated during hypoxia in mouse cardiomyocytes and in human and mouse ischemic hearts causing a detrimental lipid accumulation. To know how the gene is regulated is important for future studies. In this study, we have thoroughly mapped the 5'-flanking region of the mouse VLDLr promoter and show that the hypoxia-mediated increase in VLDLr expression is dependent on Hif-1α binding to a hypoxia responsive element (HRE) located at -162 to -158bp 5'of translation start.

Increased expression of the very low-density lipoprotein receptor mediates lipid accumulation in clear-cell renal cell carcinoma.

Clear-cell renal cell carcinoma (RCC) is, in most cases, caused by loss of function of the tumor suppressor gene von Hippel-Lindau, resulting in constitutive activation of hypoxia-inducible factor (HIF)-1α and expression of hypoxia-induced genes in normoxic conditions. Clear-cell RCC cells are characterized histologically by accumulation of cholesterol, mainly in its ester form. The origin of the increased cholesterol remains unclear, but it is likely explained by an HIF-1α-driven imbalance between cholesterol uptake and excretion.

[Comparison of two therapeutic regimes for diabetes-stricken children. Social and mental resources of the family are often crucial for the prognosis].

In a prospective, randomized intervention study, 36 children with diabetes mellitus type I were followed, the aim being to study if a family psychosocial intervention at diagnosis could improve glycemic control and minimise hospital admissions. The control group was treated initially in a hospital ward, while the whole family of the children in the study group received therapeutic and social support in an out-hospital training apartment. In the study group only, both parents reported a significant improvement of the family climate.

Influence of the initial management regimen and family social situation on glycemic control and medical care in children with type I diabetes mellitus.

It is well known that social family factors are of importance in diabetes care, but it is not clear whether the initial management regimen can buffer these factors. In a prospective, randomized intervention study, 36 children with diabetes mellitus (type I) were followed, the aim being to study if a family psychosocial intervention at diagnosis could improve glycemic control and minimize hospital admissions. The control group was treated initially in a hospital ward, while the study group received problem-based learning and family-therapeutic and social support in an out-hospital training apartment.

Extrapancreatic trypsin-2 cleaves proteinase-activated receptor-2.

Proteinase-activated receptors (PARs) are activated by proteolytic removal of a short amino terminal peptide, thus exposing a new amino terminus that functions as a tethered ligand that activates the receptor. With the aim to identify and study potential activators of PAR-2 we have developed a new method to measure proteolytic cleavage of PARs. PAR-2 was tagged with the insulin C-peptide that upon receptor cleavage is released and quantified using an ELISA.

Stimulation of proteinase activated receptor-2 causes endothelial cells to promote blood coagulation in vitro.

Proteolytically activated receptors define a new subclass among the G-protein coupled receptors. Proteinase activated receptor-2 (PAR-2), the second member to be identified of this growing receptor subclass, can be activated by trypsin and trypsin-like serine proteases such as mast cell tryptase. PAR-2 is expressed in endothelial cells.

Metabolic control in children with insulin-dependent diabetes mellitus 5 y after diagnosis. Early detection of patients at risk for poor metabolic control.

Children (n = 38) aged 3-15 y were randomly chosen, at the time of diabetes diagnosis, for conventional management at a hospital ward, or for treatment partly in a training apartment where the family was offered problem-based education and special therapeutic support. HbA1c, blood glucose stability, urinary C-peptide excretions and incidence of hypoglycaemic attacks and diabetes ketoacidosis (DKA) were monitored and some standardized, self-estimated psychological tests were performed during the first 2 y after diagnosis. During the 3 y thereafter, HbA1c, presence of DKA, microalbuminuria, retinopathy and hypertension were monitored.

Vascular effects of proteinase-activated receptor 2 agonist peptide.

Proteinase-activated receptor 2 (PAR-2) is a G protein-coupled receptor related to the thrombin receptor. PAR-2 can be activated by trypsin and by synthetic peptides corresponding to the new amino terminus generated by activating proteolytic cleavage. We show in this report that intravenous injection of PAR-2 agonist peptides has dramatic effects on arterial blood pressure in anesthetized rats.

The mouse genes for the EP1 prostanoid receptor and the PKN protein kinase overlap.

PKN is a newly discovered protein kinase that has been shown to mediate GTPase Rho dependent intracellular signalling. We show in this report that the mouse PKN gene is situated at the mouse EP1 prostanoid receptor gene locus and that the two genes are overlapping in a tail-to-tail manner. An "exon trap" strategy was used to identify the overlap phenomenon.

Ligand cross-reactivity within the protease-activated receptor family.

Recently, a second member of the protease-activated receptor (PAR) family, named PAR-2, has been identified. Similar to the thrombin receptor, PAR-2 appears to be activated by proteolytic-mediated exposure of a "tethered ligand" sequence and can also be activated by the corresponding synthetic peptides. Similarities in the amino acid sequence of the receptors' tethered ligand sequences suggest that their respective agonist peptides might not be absolutely specific for their particular receptors.

The proteinase-activated receptor 2 is induced by inflammatory mediators in human endothelial cells. Comparison with the thrombin receptor.

The proteinase-activated receptor 2 (PAR-2) belongs to the family of seven transmembrane region receptors, and, like the related thrombin receptor, it is activated by specific proteolytic cleavage of its extracellular amino terminus. It is not known which proteinase is the physiological activator of the PAR-2, but candidates can be found among the enzymes involved in the inflammatory cascade systems. Here, we have studied the effects of various mediators on the expression of the PAR-2 and the thrombin receptor in cultured human umbilical vein endothelial cells.

Family-oriented support at the onset of diabetes mellitus: a comparison of two group conditions during 2 years following diagnosis.

As part of a prospective, randomized study, the psychological effects of two different treatment regimens on the diagnosis of children and adolescents aged 3-15 years with insulin-dependent diabetes insipidus were evaluated. Conventional treatment was compared to a new regimen with a crisis programme which included a milieu therapeutic setting. A total of 38 families were randomly assigned to the 2 groups and followed over a period of 2 years after initial treatment.

Molecular cloning and functional expression of the gene encoding the human proteinase-activated receptor 2.

We previously reported the molecular cloning of a mouse guanosine-nucleotide-binding-protein-coupled receptor similar to the thrombin receptor. Since the physiological agonist was unknown, the receptor was named proteinase-activated receptor 2. We describe here the cloning and functional expression of the gene encoding the corresponding human receptor.

Molecular characterization of the mouse prostanoid EP1 receptor gene.

A partial cDNA, corresponding to the mouse prostaglandin E2 receptor subtype EP1, was isolated from mouse brain cDNA using a degenerate primer PCR strategy. Using the cDNA fragment as a probe, the EP1 receptor gene was isolated and characterized. The gene consists of three exons, of which the first is non-coding, and is contained within a 3.

The mouse proteinase-activated receptor-2 cDNA and gene. Molecular cloning and functional expression.

We have reported the cloning from mouse genomic DNA of a fragment encoding a G-protein-coupled receptor related to the receptor for the blood clotting enzyme thrombin. Like the thrombin receptor this receptor is activated by proteolytic cleavage of its extracellular amino terminus. Because the physiological agonist at the receptor was unknown, we provisionally named it proteinase-activated receptor 2 (PAR-2).

Molecular cloning of a potential proteinase activated receptor.

A DNA sequence encoding a G-protein-coupled receptor was isolated from a mouse genomic library. The predicted protein is similar in structure to the thrombin receptor and has a similar activation mechanism. When expressed in Xenopus laevis oocytes, the receptor was activated by low concentrations of trypsin (EC 3.

Expression of cellular retinoid-binding proteins during normal and abnormal epidermal differentiation.

Retinoids have important roles in growth and differentiation of epidermal cells. We have analyzed the expression of two intracellular retinoid-binding proteins, the cellular retinol-binding protein type I and the cellular retinoic acid-binding protein type I, during normal and abnormal epidermal differentiation. Both proteins were found to be expressed in normal epidermis with increasing expression from basal layer towards superficial layers.

Molecular cloning of the murine substance K and substance P receptor genes.

The peptides substance K and substance P evoke a variety of biological responses via distinct, guanosine-nucleotide-binding-regulatory-protein-coupled receptors. We have screened a murine genomic cosmid library using oligonucleotide probes and have isolated, cloned and characterized the substance K receptor and the substance P receptor genes. The coding portion of the substance K receptor gene consists of five exons distributed over 13 kbp.

Isolation and characterization of a cDNA clone corresponding to bovine cellular retinoic-acid-binding protein and chromosomal localization of the corresponding human gene.

A bovine adrenal cDNA library was constructed and a clone corresponding to cellular retinoic-acid-binding protein (CRABP) mRNA was isolated and sequenced. The insert of the clone corresponds to 75 bp of the 5' untranslated portion, the whole translated and the complete 3' untranslated portion of the bovine CRABP mRNA. A genomic Southern blot, probed with CRABP cDNA, indicated that only one copy of the gene is present in the human genome.

The complete amino acid sequence of rat beta 2-microglobulin.

The primary structure of rat beta 2-microglobulin (beta 2m) was determined. It is a polypeptide of 99 amino acids with the following sequence: IQKTPQIQVY SRHPPENGKP NFLNCYVSQF HPPQIEIELL KNGKKIPNIE MSDLSFSKDW SFYILAHTEF TPTETDVYAC RVKHVTLKEP KTVTWDRDM. The primary structure was determined by NH2-terminal sequence analysis together with sequence determination of one cyanogen bromide fragment and one tryptic peptide.

Quantitation and tissue localization of the cellular retinoic acid-binding protein.

The distribution of the cellular retinoic acid-binding protein (CRABP) in some rat tissues has been determined, and the protein has been localized by immunocytochemical techniques in sections from rat testis. In the testis CRABP was found in the seminiferous tubuli with Sertoli cells and the spermatogonia most intensely stained. All other cells of the germinal epithelium appeared largely devoid of CRABP.

Increased levels of several retinoid binding proteins resulting from retinoic acid-induced differentiation of F9 cells.

The embryonal carcinoma cell line F9 is known to differentiate when exposed to retinoic acid. We have examined the quantities of two intracellular retinoid-binding proteins in undifferentiated and differentiated F9 cells. The existence of a cell surface receptor that recognizes the plasma retinol-binding protein was also explored.