Partial Denudation Research Articles

Ultrastructural evidence of cell-mediated endothelial cell injury in cardiac transplant-related accelerated arteriosclerosis.

Accelerated arteriosclerosis secondary to chronic allograft rejection is a major long-term complication of heart transplantation. Accelerated arteriosclerosis has been associated with an endothelialitis, and the majority of the involved inflammatory cells are T lymphocytes and macrophages. Coronary arteries from six heart allograft recipients with transplant-related arteriosclerosis were examined by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Four hearts were explants from heart transplant recipients with severe accelerated arteriosclerosis who were undergoing retransplantation, and two were obtained from autopsied recipients. The patients ranged in age from 6 to 60 years (mean, 44 years). The graft survival for these six hearts ranged from 1.4 to 5.6 years (mean, 4.3 years). Lymphocytes, macrophages, and smooth muscle cells were identified by TEM in the intimas of all the vessels examined. The lymphocytes were often in contact with macrophages or in close proximity to injured endothelial cells. Areas of endothelial injury were characterized by vacuolization of endothelial cells and partial denudation of the endothelium with fibrin deposition. SEM also revealed endothelial cell injury with disorganization of the endothelium and gaps between endothelial cells. Leukocytes and platelets were often noted in these gaps. These findings suggest that accelerated arteriosclerosis in heart transplant recipients is associated with an accumulation of macrophages, lymphocytes, and smooth muscle cells in the intima as well as with lymphocyte-directed endothelial injury.

Influence of mitomycin C on endothelial monolayer regeneration in vitro.

This study examines the effect of Mitomycin C, a fungal toxin which inhibits DNA synthesis, on the regeneration of partially denuded large vessel endothelium in vitro. Monolayers of bovine pulmonary artery endothelial cells were treated with Mitomycin C prior to or immediately following partial denudation and were incubated in the continuing presence of Mitomycin C; the effects of this treatment on monolayer repair, cell proliferation, and other aspects of endothelial phenotype were monitored. Cell proliferation, DNA, RNA, and protein synthesis were all reduced in a dose dependent manner in treated cultures. Incubation with Mitomycin C for 48 h or longer resulted in reduced cell spreading, and rounding up and loss of cells from both intact and partially denuded cultures. Effects were less severe with lower doses and shorter incubation times. However, significant reductions in monolayer regeneration occurred within 8 h of incubation, sufficiently early to suggest that Mitomycin C may affect aspects of the regeneration process independent of cell proliferation. Polarization/spreading of cells at the denudation edge was monitored by fluorescence staining for golgi with C5-DMB-ceramide, and for centrioles with antibodies to tubulin. Centrioles and golgi rapidly reoriented to a location at the putative leading edge of control cultures. Mitomycin C treatment had no effect on centriole reorientation, but caused a significant delay in golgi localization. These results suggest that Mitomycin C inhibits endothelial monolayer regeneration by mechanisms independent of cell proliferation and DNA synthesis, perhaps by interfering with cell spreading or translocation at the wound edge.

Intercellular transport through a partially denuded arterial endothelial monolayer. Effect of platelets and PGI 2

Fluorescein Dextran (FD) was shown to be transported at increased rates through partially denuded endothelial monolayer. Platelet binding to the partially denuded monolayer lowered transport rates to those comparable with intact endothelium. Inhibition of transport by platelet binding was not affected by the addition of isocarbacyclin (a stable derivative of PGI 2). This result suggests that adherent platelets at the partial denudation site are sufficient to suppress transport of FD.

Complete and partial denudation of the penis following circumcision

Two cases of iatrogenic denudation of the penis following a ritual Jewish circumcision are presented. They were treated within 24 h by split thickness skin grafting. The different approaches in repair are described, and the literature is reviewed.

Evolution of a Plio-Pleistocene volcanogenic-alluvial fan: The Puye Formation, Jemez Mountains, New Mexico

The Plio-Pleistocene Puye Formation, north-central New Mexico, contains >15 km 3 of volcaniclastic alluvial sediments deposited in response to rift-margin volcanism associated with the later evolution of the Tschicoma volcanic center, northeastern Jemez Mountains. Stratigraphic and sedimentologic evidence indicates that aggradation of Puye deposits was nearly continuous and contemporaneous with graben development and establishment of the Rio Grande as the through-flowing axial drainage system in this region. Much of the Puye sediments debouched into an adjacent subsiding depocenter, resulting in near-complete preservation of this wedge-shaped volcanogenic fan. Primary-pyroclastic and reworked facies in the Puye Formation exhibit distinctive 5- to 30-m scale cyclicity directly related to volcanic activity in the northeastern Jemez highlands. Reworked-pyroclastic and conglomeratic sequences deposited by high-energy braided streams, sediment-charged sheet-floods, sediment-gravity flows, and in shallow lakes reflect markedly increased sediment loads during and following explosive eruptions. Individual sequences change markedly in character with increased distance from the source area. Analysis of these abrupt lateral and vertical variations reveals that Puye sedimentation was controlled by the influences of semiarid climate and syndepositional tectonism, although the associations that most characterize the fan resulted largely from explosive volcanism. Cessation of fan growth is attributed to waning sediment supply as a result of volcanic quiescence and to the onset of basinwide pedimentation associated with downcutting of the ancestral Rio Grande. The Puye fan therefore provides a detailed record of rift-basin alluvial sedimentation, complete with closely spaced tephrostratigraphic control, and it records the growth and partial denudation of high-standing, northeastern Jemez Mountains volcanoes.

The Thrombolytic Effects of Native Tissue-Type Plasminogen Activator (AK-124) on Experimental Canine Coronary Thrombosis

To evaluate the thrombolytic effects of the native tissue-type plasminogen activator (t-PA), the authors used a thrombus model simulating clinical situations. The native t-PA (AK-124) was obtained from human-derived normal cells. Experimental canine coronary thrombosis was produced by partial constriction and endothelial denudation of the vessel. In 19 dogs, coronary occlusive thrombus was produced. Three hours after total occlusion of the coronary artery with thrombus, the authors attempted the thrombolytic therapy in 16 dogs. Histologically, three-hour thrombus was composed of a mixture of platelet aggregates, fibrin, and blood cells. They infused 0.375 mg/kg t-PA intravenously in 7 dogs and 20,000 IU/kg urokinase (UK) in 9. Coronary recanalization was achieved in 5 (71%) with t-PA infusion and 6 (67%) with UK infusion. Plasma fibrinogen levels decreased to 76% of preinfusion value in the dogs with t-PA infusion and to 34% in those with UK infusion. Coronary reocclusion occurred in 2 dogs with t-PA and 3 with UK. Thus, the native t-PA (AK-124) can provide coronary thrombolysis without severe depletion of plasma fibrinogen levels.

SINUSOIDAL LINING CELL DAMAGE

We have previously defined viability limits in a rat transplantation model. All liver allografts stored in a simple preservation solution (NaCl 0.9%, CaCl2 2 mM) at 4 degrees C for 4 hr or at 37 degrees C for 1 hr were viable upon transplantation, but all those stored at 4 degrees C for 8 hr or at 37 degrees C for 2 hr were nonviable. Only cold-preserved, nonviable livers showed increased vascular resistance, platelet trapping and an initially low, but then high, rise in aspartate transaminase (AST) upon reperfusion, all suggesting injury to the microcirculation, with secondary injury to the hepatocyte. In the present study, we investigated the morphological changes that occur in livers stored for the defined critical times, using light and electron microscopy after perfusion-fixation. Accurate and reproducible identification of specimens as belonging to viable or nonviable and warm- or cold-preserved could be made in this way. Preservation in the cold first resulted in reversible changes consisting of cellular swelling, alterations of intracellular organelles, and partial denudation of the sinusoidal lining (cold-preserved viable group). Later, under conditions of nonviable cold preservation, detachment of cell bodies of sinusoidal lining cells with nuclear changes and almost complete denudation of the sinusoidal lining was observed. Endothelial cells of larger vessels were only injured mildly. In contrast, under conditions of warm preservation, changes involving mitochondria and later nuclei were found in hepatocytes, and blebbing was more extensive. Endothelial cells were spared relatively. We also examined livers stored in isotonic citrate solution at 4 degrees C for 8 hr and 16 hr, the critical times determined for this solution in another model of rat liver transplantation. The findings were very similar to storage in saline with respect to the changes in the sinusoidal lining cells after cold preservation for the two critical times. The results provide convincing evidence of a qualitative difference between warm and cold preservation injury, with relatively selective damage to hepatocytes or sinusoidal lining cells, respectively. Endothelial damage represents the primary event, resulting in the loss of organ viability following hypothermic storage. Thus morphology may serve as a useful viability marker after preservation.

Morphology in the Cat Ileal Mucosa Following Construction of an Ileal Reservoir or Tranposition of Patches to Different Locations

In an attempt to examine the response of the ileal mucosa to different noxious environments and to correlate the results with findings in human continent ileostomy reservoirs, cat intestine was subjected to various operative procedures: first, ileal reservoirs were constructed in continuity with the small intestine, a technique that was slightly different from that employed in human subjects, and secondly, segments or patches of ileum were transposed to the colon, the urinary bladder, or the jejunum. Morphometric evaluation was subsequently performed on these samples. The mucosa of the reservoir revealed a decrease in villus height accompanied by an increased mitotic index. Identical changes were observed when ileal segments or patches were inserted in the colon, whilst transposition to the urinary bladder resulted in similar but more pronounced alterations. When ileal patches from the colon or urinary bladder were replaced in the jejunum, the villi were once again enlarged. The epithelial cells remained normal in all cases except following transposition to the urinary bladder, where flattening of the cells or partial denudation of the villus tips was encountered. The changes observed represent a classical hyper-regenerative transformation of the mucosa, and correspond closely with the changes recorded in human continent ileostomy reservoirs. Furthermore, the reversibility of such alterations has been demonstrated. The experimental design permitted the exclusion of intraluminal pressure, dilatation, and nervous and vascular derangements as the cause of the transformation; it is concluded that the intraluminal environment is the factor most probably responsible for such structural alterations.

An Early Tertiary Surface in Wiltshire

A study of early Tertiary and Pleistocene gravels on Salisbury Plain demonstrates the nature of the early Tertiary surface there and indicates its preservation in the contemporary landscape on the highest summits of the Chalk. The composition of the Pleistocene gravels is treated as a guide to the character and former extent of the early Tertiary outcrop, of which only a few isolated and disturbed outliers remain. The early Tertiary gravels show affinities with the Tertiary outcrop in the western part of the Hampshire Basin. They appear to have rested on a polycyclic surface from which, in the later stages of its development, much of the Upper Chalk had been eroded. This surface is now represented in a small number of residual summits rising above the more extensively preserved mid-Tertiary surface. THE PRINCIPAL hypotheses of landscape evolution in southern England (P. Pinchemel, 1954; S. W. Wooldridge and D. L. Linton, 1955) disagree most significantly in the interpretation of the early Tertiary period. The scope for disagreement is evident on Salisbury Plain, where undoubted Tertiary deposits are absent and the configuration of the sub-Tertiary surface is correspondingly doubtful. This problem, on Salisbury Plain and elsewhere, was clearly appreciated by the officers of the Geological Survey. A. J. Jukes-Browne (1906) regarded the clay-with-flints as a relic of the Reading Beds and suggested that, where it occurs, the sub-Eocene surface is preserved. His conclusions implied that the elevation and partial denudation of the Pewsey anticline, and related folds, were of pre-Tertiary date. H. J. 0. White (1907) inferred uniform overstep of the Tertiaries from the Hampshire Basin northward across successively lower zones of the Chalk, and rejected the pre-Tertiary folding of the Chalk. Both geologists appear to have regarded the sub-Tertiary surface as an extension of the sub-Reading Beds surface. The implications of White's account are manifest in the work of Wooldridge and Linton. Their sub-Eocene contours (1955, Fig. 5) show a surface corrugated by Alpine structures and imply that the Alpine movements occurred after the modelling of the sub-Eocene surface. It is not clear whether the Chalk retained a mantle of Eocene sediments at the time of the folding; or whether these sediments were already partly denuded and the Chalk subject to erosion. Linton (1956) suggests that renewed erosion of the Chalk is likely to have occurred before the folding, but most of the erosion, and in particular the denudation of the Alpine folds, is inevitably referred by Wooldridge and Linton to the mid-Tertiary cycle. Over the crests of the principal anticlines this implies the removal of a few hundred metres of material during this cycle. The sub-Eocene surface is therefore identified by Wooldridge and Linton as a limited facet on the Chalk dip-slope near the present boundary of the Eocene outcrop, whereas the summit planation of the Chalk they regard as a product of the mid-Tertiary cycle. This view of Tertiary events is challenged by Pinchemel (1954), who accepts the extensive survival of an early Tertiary surface on the Chalk summits of southern England and suggests that the surface is of polycyclic origin. More recently M. J. Clark, J. Lewin and R. J. Small (1967), arguing from the distribution of Eocene debris and from the nature of the relief, have also concluded that the hill-top peneplain, at least near Marlborough, may be 'the outcome of a composite Eogene cycle'.

Mucosal denudation (stripping) for bladder papillomatosis.

Ten patients with papillomatosis of the urinary bladder were treated with total or partial mucosal denudation. Regeneration of the mucosa took place within four or five weeks as normal transitional epithelium. Papillomatosis recurred in three cases. In two cases the recurrence appeared in presumably residual bladder epithelium, and in the third patient the operation revealed papillomatous carcinoma (stage T 1, grade 2). Severe contraction of the bladder occurred in one patient and necessitated ileocystostomy.The rate of recurrence during an observation period averaging 20 months seems to be reasonably low. The risk of bladder contracture can presumably be reduced by limiting the operation to subtotal or partial stripping.

Healing after partial denudation of the alveolar process.

Healing after partial denudation of the alveolar process.

On a well-marked Horizon of Radiolarian Rocks in the Lower Culm Measures of Devon, Cornwall, and West Somerset

On a well-marked Horizon of Radiolarian Rocks in the Lower Culm Measures of Devon, Cornwall, and West Somerset