Biomedical subjects

A Jurek

Publications and source records attributed to A Jurek.

At least 19 recordsLinked to original sources

PubMed1997

Vitamin C blocks inflammatory platelet-activating factor mimetics created by cigarette smoking.

Cigarette smoking within minutes induces leukocyte adhesion to the vascular wall and formation of intravascular leukocyte-platelet aggregates. We find this is inhibited by platelet-activating factor (PAF) receptor antagonists, and correlates with the accumulation of PAF-like mediators in the blood of cigarette smoke-exposed hamsters. These mediators were PAF-like lipids, formed by nonenzymatic oxidative modification of existing phospholipids, that were distinct from biosynthetic PAF. These PAF-like lipids induced isolated human monocytes and platelets to aggregate, which greatly increased their secretion of IL-8 and macrophage inflammatory protein-1alpha. Both events were blocked by a PAF receptor antagonist. Similarly, blocking the PAF receptor in vivo blocked smoke-induced leukocyte aggregation and pavementing along the vascular wall. Dietary supplementation with the antioxidant vitamin C prevented the accumulation of PAF-like lipids, and it prevented cigarette smoke-induced leukocyte adhesion to the vascular wall and formation of leukocyte-platelet aggregates. This is the first in vivo demonstration of inflammatory phospholipid oxidation products and it suggests a molecular mechanism coupling cigarette smoke with rapid inflammatory changes. Inhibition of PAF-like lipid formation and their intravascular sequela by vitamin C suggests a simple dietary means to reduce smoking-related cardiovascular disease.

Animals↗

PubMed1997

Postural imbalance and vibratory sensitivity in patients with idiopathic scoliosis: implications for treatment.

Sporadic research reports of decreased proprioception and balance problems have been reported in subjects with idiopathic scoliosis, yet these sensory motor deficits have not been addressed in conservative clinical management programs. The purpose of this study was to compare both balance reactions and vibratory sensitivity (as an estimate of proprioception) in patients with idiopathic scoliosis (N = 24) and age-matched controls (N = 24). Balance was measured by the ability to pass a series of simple static and complex sensory-challenged balance tasks. Vibratory thresholds were measured with the Bio-Thesiometer at the cervical spine, wrist, and foot. Compared with age-matched controls, regardless of curve severity or spinal fusion, the subjects with idiopathic scoliosis had similar simple static balance responses when the somatosensory system was stable (with or without vision or head turning), but they were significantly more likely to fail the complex, sensory-challenged balance tasks when the somatosensory system was challenged by an unstable position of the feet, particularly when the eyes were closed. The vibratory thresholds were similar in subjects with scoliosis and their age-matched controls, but individuals with moderate to severe scoliosis (> 25 degrees) had significantly higher vibratory thresholds than those with mild curves. These findings suggest there may be problems with postural righting in patients with idiopathic scoliosis, particularly when the balance task challenges the vestibular pathways. Although vibration sensitivity did not distinguish normal healthy individuals from individuals with idiopathic scoliosis, those with more severe scoliotic curves appear to have a high threshold to vibration. These balance and vibratory differences could either be interpreted as etiologic risk factors or as consequences of spinal asymmetry. In either case, given that curves can continue to progress even into the adult years, improving the ability to right the body with gravity could help maintain the balance of the spine despite structural asymmetry.

Adolescent↗

PubMed1992

Structure-affinity relationships of retinoids with embryonic cellular retinoic acid-binding protein.

Separation and quantitation of cellular retinoic acid-binding protein (CRABP) in embryonic and fetal hamster tissues was accomplished with high-performance size-exclusion chromatography. Binding affinity of 26 retinoids was established by in vitro displacement of high specific activity all-trans-[3H2]retinoic acid from fetal CRABP. The CRABP concentration in presomite-to-early somite (Day 8) hamster embryos was 1.9 pmol/mg cytosolic protein and increased to 7.5 pmol/mg protein in Day 13 fetuses; CRABP concentrations subsequently declined as gestation progressed. CRABP was located primarily in fetal brain and skin (5.8 +/- 0.3 and 2.2 +/- 0.1 pmol/mg protein, respectively), whereas only trace concentrations were found in fetal liver, placenta, and maternal uterus. Retinoids that could displace all-trans-retinoic acid from CRABP had a free acid at the polar terminus (or were carboxylate esters that were readily hydrolyzed to the corresponding free acid) and had a hydrophobic ring at the distal position. The ligand specificity of the CRABP studied here suggests that this protein was analogous to the CRABP I isoform. The in vitro binding affinities of teratogenic retinoids that competed for embryonic CRABP failed to correlate directly with relative teratogenic potency. In some instances, the latter observation can be related to extensive in vivo biotransformation of retinoids to multiple teratogenic metabolites and to retinoid persistence in the embryo. Three analogs containing a free carboxy terminus, SRI 5898-21, SRI 7323-78, and SRI 6153-40, were identified with high teratogenic potency but failed to bind fetal hamster CRABP. The structure-activity and binding data of the analogs studied here indicate that many, if not most, teratogenic retinoids (or their acidic metabolites) bind with embryonic/fetal CRABP, but the present data question the role for CRABP in their teratogenic mechanism of action.

Animals↗

PubMed1982