Microvascular closure in malignant histiocytosis.

Two patients with malignant histiocytosis were found to have capillary occlusion by aggregates of neoplastic histiocytes, in skeletal muscle in one, and in renal glomeruli in the other. One patient had clinical evidence of similar occlusions in the arterioles and capillaries of the ocular fundi. Occlusion of small vessels by tumour cells may explain the confusion of both patients.     

Studies on closure of the ductus arteriosus. XI. Ductal closure by a prostaglandin synthetase inhibitor

Intrauterine contraction of the ductus arteriosus in fetuses followed a single oral dose of 15 mg/kg indomethacin to pregnant rats 12 or 18 h prior to delivery. This ductal contraction studied by the whole-body freezing technique was markedly pronounced up to 30 min after delivery. Blood gas measurements showed a low pH at 30 min which returned to normal at 120 min. Cyanosis was persistant in the indomethacin groups. Intrauterine ductal closure may be a danger to the fetus and subsequent postnatal adjustment. The present results need confirmation in other species to predict a similar risk in the human fetus.     

Domain closure in mitochondrial aspartate aminotransferase.

The subunits of the dimeric enzyme aspartate aminotransferase have two domains: one large and one small. The active site lies in a cavity that is close to both the subunit interface and the interface between the two domains. On binding the substrate the domains close together. This closure completely buries the substrate in the active site and moves two arginine side-chains so they form salt bridges with carboxylate groups of the substrate. The salt bridges hold the substrate close to the pyridoxal 5'-phosphate cofactor and in the right position and orientation for the catalysis of the transamination reaction. We describe here the structural changes that produce the domain movements and the closure of the active site. Structural changes occur at the interface between the domains and within the small domain itself. On closure, the core of the small domain rotates by 13 degrees relative to the large domain. Two other regions of the small domain, which form part of the active site, move somewhat differently. A loop, residues 39 to 49, above the active site moves about 1 A less than the core of the small domain. A helix within the small domain forms the "door" of the active site. It moves with the core of the small domain and, in addition, shifts by 1.2 A, rotates by 10 degrees, and switches its first turn from the alpha to the 3(10) conformation. This results in the helix closing the active site. The domain movements are produced by a co-ordinated series of small changes. Within one subunit the polypeptide chain passes twice between the large and small domains. One link involves a peptide in an extended conformation. The second link is in the middle of a long helix that spans both domains. At the interface this helix is kinked and, on closure, the angle of the kink changes to accommodate the movement of the small domain. The interface between the domains is formed by 15 residues in the large domain packing against 12 residues in the small domain and the manner in which these residues pack is essentially the same in the open and closed structures. Domain movements involve changes in the main-chain and side-chain torsion angles in the residues on both sides of the interface. Most of these changes are small; only a few side-chains switch to new conformations.(ABSTRACT TRUNCATED AT 400 WORDS)     

Wound closure in foetal rat skin.

Foetal rat skin rapidly closes an open wound in organ culture and in vivo, this possibly being unique to organs still in the morphogenetic stage. In the present study, examination was made of morphological changes in foetal rat skin during closure of open wounds inflicted at day 16 of gestation. Phase-contrast microscopy of open-wounded skin cultured in vitro indicated inward spreading of the peripheral skin to be responsible for wound closure. Wound closure in vitro was inhibited by cytochalasin B (10 micrograms/ml), not by hydroxyurea (2 mM), indicating prenatal wound closure to be mediated by regulation of the microfilament system rather than cell proliferation. During wound closure in vitro and in vivo, light and scanning electron microscopy of the peripheral skin showed cells in the periderm, the outermost layer of the foetal epidermis, to elongate centripetally and en masse, whereas the shape of underlying epidermal cells not to change. Numerous spindle-shaped cells and fibrous matrices in the mesenchyme were redistributed, becoming oriented along the wound edge. Following isolation of the mesenchyme and epidermis by treatment with Dispase and separate culturing, the capacity for wound closure in vitro was found to be retained only by the mesenchyme. Cellular activity within the mesenchyme, rather than in the epidermis, would thus appear essential to wound closure in foetal rat.     

Demonstration of airway closure in man.

After partial equilibration of the lung with a N2O gas mixture absorption of N2O by the pulmonary circulation results in a flow of gas into the lungs during breath holding. A bolus of 133Xe introduced at the mouth at the beginning of the breath hold is carried in by the gas flow and distributed according to regional perfusion. In three subjects, breath holding at FRC, apex-to-base distribution of a 133Xe bolud delivered by N2O absorption (Xecar) was similar to that of a bolus injected intravenously (Xeiv). Near RV however, much less of Xecar penetrated into dependent zones than expected from the distribution of Xeiv. In fact, distribution of Xecar did not differ from that of a slowly inhaled bolus. Correction for Compton scatter in the chest wall, measured in one subject, accounted only in part for the radioactivity recorded over dependent lung regions. The findings indicate that near RV some but not all of the dependent airways must be closed. Furthermore, the distribution of airway closure completely accounts for the distribution of a bolus inhaled from RV.     

Hospital admissions before and after shipyard closure.

To determine the effect of job loss on health an investigation was made of admissions to hospitals in 887 men five years before and three years after the closure of a Danish shipyard. The control group comprised 441 men from another shipyard. The information on hospital admissions was obtained from the Danish national register of patients. The relative risk of admission in the control group dropped significantly in terms of the number of men admitted from the study group from 1.29 four to five years before closure to 0.74 in the three years after closure. This was especially true of admissions due to accidents (1.33 to 0.46) and diseases of the digestive system (4.53 to 1.03). For diseases of the circulatory system, particularly cardiovascular diseases, the relative risk increased from 0.8 to 1.60, and from 1.0 to 2.6 respectively. These changes in risk of illness after redundancy are probably a consequence of a change from the effects of a high risk work environment to the effects of psychosocial stresses such as job insecurity and unemployment.     

SPARC-null mice exhibit accelerated cutaneous wound closure.

Expression of SPARC (secreted protein acidic and rich in cysteine; osteonectin, BM-40), an extracellular matrix (ECM) associated protein, is coincident with matrix remodeling. To further identify the functions of SPARC in vivo, we have made excisional wounds on the dorsa of SPARC-null and wild-type mice and monitored closure over time. A significant decrease in the size of the SPARC-null wounds, in comparison to that of wild-type, was observed at Day 4 and was maximal at Day 7. Although substantial differences in the percentage of proliferating cells were not apparent in SPARC-null relative to wild-type wounds, primary cultures of SPARC-null dermal fibroblasts displayed accelerated migration, relative to wild-type fibroblasts, in wound assays in vitro. Although the expression of collagen I mRNA in wounds, as measured by in situ hybridization (ISH), was not significantly different in SPARC-null vs wild-type mice, the collagen content of unwounded skin appeared to be substantially lower in the SPARC-null animals. By hydroxyproline analysis, the concentration of collagen in SPARC-null skin was found to be half that of wild-type skin. Moreover, we found an inverse correlation between the efficiency of collagen gel contraction by dermal fibroblasts and the concentration of collagen within the gel itself. We propose that the accelerated wound closure seen in SPARC-null dermis results from its decreased collagen content, a condition contributing to enhanced contractibility.     

Airway closure with high PEEP in vivo.

When airway smooth muscle is contracted in vitro, the airway lumen continues to narrow with increasing concentrations of agonist until complete airway closure occurs. Although there remains some controversy regarding whether airways can close in vivo, recent work has clearly demonstrated that, if the airway is sufficiently stimulated with contractile agonists, complete closure of even large cartilaginous conducting airways can readily occur with the lung at functional residual capacity (Brown RH and Mitzner W. J Appl Physiol 85: 2012-2017, 1998). This result suggests that the tethering of airways in situ by parenchymal attachments is small at functional residual capacity. However, at lung volumes above functional residual capacity, the outward tethering of airways should increase, because both the parenchymal shear modulus and tethering forces increase in proportion to the transpulmonary pressure. In the present study, we tested whether we could prevent airway closure in vivo by increasing lung volume with positive end-expiratory pressure (PEEP). Airway smooth muscle was stimulated with increasing methacholine doses delivered directly to airway smooth muscle at three levels of PEEP (0, 6, and 10 cmH(2)O). Our results show that increased lung volume shifted the airway methacholine dose-response curve to the right, but, in many airways in most animals, airway closure still occurred even at the highest levels of PEEP.     

Surfactant effects in model airway closure experiments.

The capillary instability that occurs on an annular film lining a tube is studied as a model of airway closure. Small waves in the film can amplify and form a plug across the tube. This dynamical behavior is studied using theoretical models and bench-top experiments. Our model predicts the initial growth rate of the instability and its dependence on surfactant effects. In experiments, an annular film is formed by infusion of water into an initially oil-filled glass capillary tube. The thickness of the oil film varies with the infusion flow rate. The instability growth rate and closure time are measured for a range of film thicknesses. Our theory predicts that a thinner film and higher surfactant activity enhance stability; surfactant can decrease the growth rate to 25% of its surfactant-free value. In experiments, we find that surfactant can decrease the growth rate to 20% and increase the closure time by a factor of 3.8. Functional values of a critical film thickness for closure support the theory that it increases in the presence of surfactant.     

DuctOcclud--implant for transcatheter closure of patent ductus arteriosus.

The DuctOcclud implant is a metal coil device designed for transcatheter closure of small to moderate size patent ductus arteriosus, a Congenital Heart Disease in which a vessel-like communication between the aorta and the pulmonary artery persists after birth. The paper describes the design of the device, its delivery system, and the implant procedure. It also reviews and reports the experimental and the clinical experiences accumulated utilizing the device for occlusion of patent ductus arteriosus.