A study of the clinical and radiological features in a cohort of 93 patients with a COL2A1 mutation causing spondyloepiphyseal dysplasia congenita or a related phenotype

Type 2 collagen disorders encompass a diverse group of skeletal dysplasias that are commonly associated with orthopedic, ocular, and hearing problems. However, the frequency of many clinical features has never been determined. We retrospectively investigated the clinical, radiological, and genotypic data in a group of 93 patients with...

Inhibition of the central melanocortin system decreases brown adipose tissue activity

The melanocortin system is an important regulator of energy balance, and melanocortin 4 receptor (MC4R) deficiency is the most common monogenic cause of obesity. We investigated whether the relationship between melanocortin system activity and energy expenditure (EE) is mediated by brown adipose tissue (BAT) activity. Therefore, female APOE∗3...

Bace1 activity in cerebrospinal fluid and its relation to markers of ad pathology

Several studies have shown that reduced amyloid-β 1-42 (Aβ {42}) and increased tau levels in cerebrospinal fluid (CSF) reflect increased Alzheimer's disease (AD) pathology in the brain. β-site APP cleaving enzyme (BACE1) is thought to be the major β-secretase involved in Aβ production in the brain, and therefore we investigated the relation...

Collagen turnover in normal and degenerate human intervertebral discs as determined by the racemization of aspartic acid

Knowledge of rates of protein turnover is important for a quantitative understanding of tissue synthesis and catabolism. In this work, we have used the racemization of aspartic acid as a marker for the turnover of collagen obtained from healthy and pathological human intervertebral disc matrices. We measured the ratio of the D- and L-isomers in...

Single amino acid residue changes in subsite - 1 of inulosucrase from Lactobacillus reuteri 121 strongly influence the size of products synthesized

Bacterial fructansucrase enzymes belong to glycoside hydrolase family 68 and catalyze transglycosylation reactions with sucrose, resulting in the synthesis of fructooligosaccharides and/or a fructan polymer. Significant differences in fructansucrase enzyme product specificities can be observed, i.e. in the type of polymer (levan or inulin)...

Aggrecan turnover in human intervertebral disc as determined by the racemization of aspartic acid

We have used the racemization of aspartic acid as a marker for the "molecular age" of aggrecan components of the human intervertebral disc matrix (aggregating and non-aggregating proteoglycans as well as the different buoyant density fractions of aggrecan). By measuring the D/L Asp ratio of the various aggrecan species as a function of age and...

Biochemical and molecular characterization of Lactobacillus reuteri 121 reuteransucrase

Lactobacillus reuteri strain 121 uses sucrose for synthesis of a unique, soluble glucan ('reuteran') with mainly α-(1→4) glucosidic linkages. The gene (gtfA) encoding this glucansucrase enzyme had previously been characterized. Here, a detailed biochemical and molecular analysis of the GTFA enzyme is presented. This is believed to be the first...

Bioavailability of tryptophan from a single oral dose of a trytophan-enriched peptide mixture in healthy men

The aim of the study was to investigate the bioavailability of tryptophan (Trp) from a Trp-enriched peptide mixture in healthy men. A second objective was to investigate the effect of this Trp-enriched protein hydrolysate on potential parameters of serotonergic activity. serum serotonim melatonin and prolactin and urinary 5-hydroxyindol-acetic...

Age-related accumulation of the advanced glycation endproduct pentosidine in human articular cartilage aggrecan: The use of pentosidine levels as a quantitative measure of protein turnover

During aging, non-enzymatic glycation results in the formation and accumulation of the advanced glycation endproduct pentosidine in long-lived proteins, such as articular cartilage collagen. In the present study, we investigated whether pentosidine accumulation also occurs in cartilage aggrecan. Furthermore, pentosidine levels in aggrecan...

Beneficial effects of TCP on soman intoxication in guinea pigs: Seizures, brain damage and learning behaviour

Poisoning with the potent nerve agent soman produces a cascade of central nervous system (CNS) effects characterized by severe convulsions and eventually death. In animals that survive a soman intoxication, lesions in the amygdala, piriform cortex, hippocampus and thalamus can be observed. In order to examine the mechanisms involved in the...

Effect of collagen turnover on the accumulation of advanced glycation end products

Collagen molecules in articular cartilage have an exceptionally long lifetime, which makes them susceptible to the accumulation of advanced glycation end products (AGEs). In fact, in comparison to other collagen-rich tissues, articular cartilage contains relatively high amounts of the AGE pentosidine. To test the hypothesis that this higher AGE...

Mutational analysis of pea lectin: Substitution of Asn125 for Asp in the monosaccharide-binding site eliminates mannose/glucose-binding activity

As part of a strategy to determine the precise role of pea (Pisum sativum) lectin, Psl, in nodulation of pea by Rhizobium leguminosarum, mutations were introduced into the genetic determinant for pea lectin by site-directed mutagenesis using PCR. Introduction of a specific mutation, N125D, into a central area of the sugar-binding site resulted...

Involvement of aspartic and glutamic residues in kringle-2 of tissue-type plasminogen activator in lysine binding, fibrin binding and stimulation of activity as revealed by chemical modification and oligonucleotide-directed mutagenesis

Glutamate metabolism in ageing rat brain

The metabolism of glutamate, taken as an index of the metabolic state of the brain, was studied in brains of 3-, 12- and 30-month-old rats. Following the injection of a mixture of [3H]acetate and d-[2-14C]glucose, the brain levels of glutamate and aspartate were decreased in 30-month-old rats when compared with those of 3-month-old rats. No...