The biochemical and clinical aspects of the participation of granulocytes and their proteinases in a vascular wall lesion

Some components of plasma and granulocyte proteolytic system, granulocyte activation degree were evaluated in 15 patients with nonspecific aortic arteritis (NAA) and 12 hereditary hypercholesterolemia (HHC) patients. Catepsin G activity in blood plasma of NAA and HHC patients was higher than in donors 8-9 and 6-fold, respectively (p < 0.001). Granulocyte collagenase activity, spontaneous NBT test values in them were higher than in donors 6 and 4-fold (p < 0.02 and p < 0.01, respectively), 2-fold (p < 0.005 and p < 0.001, respectively). The data obtained confirm the suggestion on the presence of an inflammatory component not only in pathogenesis of NAA, but also in HHC causation.     

Maternal prepregnant weight and weight gain: relationship to placental microstructure and morphometric oxygen diffusion capacity

This study examines the effects of maternal prepregnant weight and gestational weight gain on the size, microstructure, and function of the human placenta. Standard gross, histologic, and histomorphometric techniques were used to examine placentas obtained from the deliveries of 77 poor, black 12- to 30-year-old subjects in relation to maternal prepregnant weight and the rate of maternal weight gain during gestation. The weight, volume, and fetal capillary surface area of the placenta increased significantly in relation to both maternal prepregnant weight and the rate of maternal weight gain during gestation. Prepregnant weight was a more important determinant of placental size and fetal capillary surface area than was the rate of maternal weight gain. The rate of maternal weight gain was a more important determinant of the density of fetal capillary tissues within the placenta and of placental resistance to oxygen diffusion than was prepregnant weight. Both maternal prepregnant weight and the rate of maternal weight gain during gestation relate positively to the size of the placenta, but they have different, potentially complementary effects on placental microstructure and function.     

Skeletal muscle cell-derived insulin-like growth factor (IGF) binding proteins inhibit IGF-I-induced myogenesis in rat L6E9 cells

The insulin-like growth factors (IGFs) stimulate the differentiation of skeletal muscle cells. IGF binding proteins (IGFBPs), which are expressed by skeletal muscle cells, may enhance or inhibit IGF actions. To explore the role of skeletal muscle-derived IGFBPs in IGF-induced myogenesis, we compared the differentiation-inducing effects of IGF-I and des(1-3)IGF-I in rat L6E9 skeletal myoblasts. Des(1-3)IGF-I is a naturally occurring IGF-I analog with markedly reduced affinity for IGFBPs but with an affinity for the IGF-I receptor that is comparable to that for native IGF-I. We find that rat L6E9 cells produce principally IGFBP-4 and BP-6, with a minor component of IGFBP-5. Both IGFBP-4 and BP-6 accumulate during differentiation and increase further in response to IGF-I or des(1-3)IGF-I treatment. We find that an IGF-I analog with reduced affinity for IGFBPs is significantly more potent than native IGF-I in stimulating myogenesis (as assessed by myogenin messenger RNA abundance and muscle creatine kinase activity), indicating that IGFBPs expressed by skeletal muscle cells inhibit differentiation induced by IGF-I. In view of the relative abundance of IGFBP-4, its relatively high affinity for IGF-I and the low affinity of IGFBP-6 for IGF-I, it is likely that the inhibitory effect of rat skeletal muscle-derived IGFBPs on IGF-I-induced myogenesis is mediated principally by IGFBP-4.     

Quantitation of D antigen content in inactivated poliovirus vaccine derived from wild-type or sabin strains

We studied the ontogenetic development of renal alpha 1-, alpha 2-, and beta-adrenergic receptors and their coupling to inositol phosphate and cyclic AMP formation in spontaneously hypertensive and normotensive Wistar-Kyoto rats. alpha 1-, alpha 2-, and beta-Adrenergic receptor number was significantly increased in hypertensive compared with normotensive rats, but the increase did not precede blood pressure elevation. Despite increased alpha 1-adrenergic receptors, basal and norepinephrine-stimulated inositol phosphate formation remained unchanged in all age groups. Rat kidney contains alpha 1A- and alpha 1B-adrenergic receptors coupling to inositol phosphate formation by different mechanisms, but the relative contribution of alpha 1A- and alpha 1B-adrenergic receptors to norepinephrine-stimulated inositol phosphate formation was similar in normotensive and hypertensive rats. Despite increased beta-adrenergic receptors, basal, isoproterenol-, and forskolin-stimulated cyclic AMP accumulation was similar in normotensive and hypertensive rats. We conclude that the number but not the functional responsiveness of renal adrenergic receptors increases in spontaneously hypertensive rats. Thus, the additional receptors are unlikely to contribute to the pathophysiology of elevated blood pressure in this model.     

Extraembryonic expression of the human MHC class I gene HLA-G in transgenic mice. Evidence for a positive regulatory region located 1 kilobase 5' to the start site of transcription

Trophoblast, the only fetal tissue in direct contact with maternal cells, fails to express the polymorphic HLA class I molecules HLA-A and -B, but does express the nonpolymorphic class I molecule HLA-G. It is thought that HLA-G may provide some of the functions of a class I molecule without stimulating maternal immune rejection of the fetal semiallograft. As a first step in identifying the cis-acting DNA regulatory elements involved in the control of class I expression by extraembryonic tissue, several types of transgenic mice were produced. Two HLA-G genomic fragments were used, 5.7 and 6.0 kb in length. These included the entire HLA-G coding region, 1 kb of 3' flanking sequence, and 1.2 or 1.4 kb of 5' flanking sequence, respectively. A hybrid transgene, HLA-A2/G, was produced by replacing the 5' flanking sequence, first exon, and early first intron of HLA-G with the corresponding elements of HLA-A. Comparison of transgene mRNA expression patterns seen in HLA-A2/G and HLA-G transgenic mice suggests that 5' flanking sequences are largely responsible for the differing patterns of expression typical of the classical class I and HLA-G genes. Studies comparing the extraembryonic HLA-G expression levels of founder embryos transgenic for either the 5.7- or 6.0-kb HLA-G transgene showed that the 6.0-kb transgene directed HLA-G expression far more efficiently than did the 5.7-kb HLA-G transgene, producing extraembryonic HLA-G mRNA levels similar to those seen in human extraembryonic tissues. The results of these studies suggest that the 250-bp fragment present at the extreme 5' end of the 6.0-kb HLA-G transgene and absent from the 5.7-kb HLA-G transgene contains an important positive regulatory element. This 250-bp fragment lies further upstream than any of the previously documented class I regulatory regions and may function as a locus control region.     

A perceptual analysis of viscosity

The perception of viscosity was studied using the contralateral limb-matching procedure in which subjects adjusted the viscosity of a motor connected to the wrist of one (matching) arm until it was perceived to be the same as that of the motor attached to the other (reference) arm. Two servo-controlled electromagnetic linear motors with computer-controlled viscosity were used to present viscosities ranging in amplitude from 2 to 1024 N.s/m to 11 subjects. Ten different viscosities were matched by subjects, and there were ten repetitions of each stimulus amplitude. The psychophysical function relating the reference to matching viscosity was linear (99% variance accounted for), and the accuracy with which the viscosities were matched (slope of 0.88) paralleled that reported previously for force, limb position and stiffness. The Weber fraction for viscosity was 0.34, which is 50% larger than that measured for stiffness and over twice that reported for force. An analysis of the movements and forces generated to perceive the reference viscosity revealed that subjects did not vary the amplitude of the movements and typically made very small excursions of the forearm, but that both the velocity of the movements and force changed significantly as a function of the reference viscosity. These findings were interpreted as indicating that the human proprioceptive system is capable of integrating information regarding force and movement velocity so as to perceive the viscosity of a mechanical system connected to the limbs, but that its sensitivity to changes in viscosity is much less than would be predicted from its capacity to detect variations in muscle force and limb movement.