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Biomedical subjects

R E Bulger

Publications and source records attributed to R E Bulger.

At least 73 records · Page 4Linked to original sources

Unilateral obstructive nephropathy in the rabbit. II. Late morphologic changes.

The late histologic and ultrastructural effects of complete unilateral ureteral obstruction in the rabbit kidney were studied from 7 to 32 days postobstruction. Papillary necrosis occurred in all animals by the 7th day. There was progressive widening of the cortical interstitial space with proliferation of fibroblasts. Increased interstitial collagen fibers first became apparent on the 7th day and showed a progressive increase with time. The fibroblasts underwent myofibroblast transformation beginning on the 7th day. All segments of the nephron showed ultrastructural evidence of sublethal cell injury with loss of cell specialization. The dedifferentiation of the tubular cells was associated with a repetitive formation of new lamellae of basement membrane on the luminal side of the original basement membranes beginning on the 16th day of obstruction. These morphologic changes are discussed in terms of the physiologic changes previously reported in this model and the known clinical abnormalities found in obstructive uropathy.

Animals↗

Energy dispersive x-ray microanalysis of mitochondrial deposits in sideroblastic anemia.

Energy dispersive x-ray microanalysis was used to analyze mitochondrial and lysosomal iron-containing deposits in sideroblastic anemia. Although it has been previously known that these deposits contain iron by inference from Prussian blue staining, the possible presence of other cations as well as the nature of the anions present has not been identified. The results show that the mitochondrial deposits in erythroid cells have peaks for iron and phosphorus indicating that they do not represent calcifications which commonly occur following injury and that the principal anion may be phosphorus. Studies of hemosiderin and ferritin aggregates in lysosomes of macrophages in the same bone marrow samples again reveal similar peaks for iron and phosphorus. The results also indicate the probable similarity of mitochondrial and macrophage deposists although ferritin itself was never identified in the mitochondrial deposits. The results illustrate the potential of this method for diagnostic and investigative pathology.

Aged↗

Hypovolemic models of acute tubular necrosis in the rat kidney.

Studies were undertaken to determine whether a hypotensive episode under variable conditions is capable of inducing experimental acute renal failure in rats. Animals were subjected to hypovolemic shock by withdrawing volumes of blood necessary to maintain a systolic pressure of 30-40 mm Hg for 105-110 min. The blood was then reinfused and the animal was allowed to recover for 48 h prior to sacrifice. In an attempt to increase the injury, a second group of animals was salt-depleted prior to injury, a third group was volume-depleted by being deprived of H2O for 72 h prior of injury, a fourth group received 7.5 mg/kg indomethacin 30 min prior to injury, and a fifth group had 30% of the blood which was removed to produce shock hemolyzed and returned following the injury. In all groups examined, light microscopy revealed a moderate to severe acute tubular necrosis localized mainly in the outer stripe of the outer zone as defined by Peter (1909). Tubular damage was confined to the medullary pars recta of the proximal tubule and only in the most severe cases did injury involve the cortical pars recta and pars convoluta. Casts were present in the distal tubules and collecting ducts. Despite these significant histologic alterations, BUN values from all experimental groups remained within control levels. These studies clearly show that extensive necrosis of the medullary pars recta can be dissociated from the development of acute renal failure.

Acute Kidney Injury↗

Detection of ion shifts in proximal tubule cells of the rat kidney using x-ray microanalysis.

The present study represents an attempt to combine scanning transmissions electron microscopy and x-ray microanalysis on thin sections at the intracellular level using kidney tubules in both normal and altered conditions. The results show that semi-quantitative estimates made from X-ray microanalysis can predict the pattern of electrolyte change both in direction and degree; these estimated agree with previously determined chemical analysis of identically treated tissue. Before these promising results can be extended to quantitative intracellular compartment analysis, further work is needed in several areas including preparation of adequate standards, improved ultracryomicrotomy techniques, improvement of contrast of ultrathin frozen sections and standardization in computing background measurements.

Animals↗

Effects of transient hypotension on the structure and function of rat kidney.

The immediate effects of renal structure and function of 60 or 90 min of hypotension and the effects of one to four days of recovery were studied in the rat. An initial diuresis occurred during the first day after hypotension, followed by decreased urine volumes. Along with the diuresis, the animals secreted a hypo-osmolar urine for two days following hypotension, which returned to a normal concentration at three days. Twenty four hour urine sodium excretion was depressed during the first and second days after hypotension while potassium excretion was no different from that of control animals. The morphologic alterations of tissue fixed immediately following 60 and 90 min of hypotension were greatest in the pars recta of the proximal tubule but were also seen focally in the pars convoluta. The cellular changes included dilated endoplasmic reticulum clumped nuclear chromatin, swollen mitochondria with small flocculent densities, and the formation of multivesicular bodies. One day after the hypotension, death cell and necrosis were observed extensively in the pars recta. This study describes an experimental model for the study of the renal effects of hypovolemic shock in rats.

Animals↗

Proximal tubule tendrils: fact or artefact.

Tendrils have been reported to radiate from luminal surfaces of proximal tubules in rat kidneys by Andrews and Porter ('74) using scanning microscopy, but they were not seen by Bulger et al. ('74). In this study, the perfusion procedure of Andrews and Porter was re-investigated. Tendrils were found only in regions which had characteristics of poor fixation. They were especially prominent if the perfusion pressure was purposely allowed to fall and subsequently increased to re-expand the tubules. The tendrils could then be seen in all portions of the proximal convoluted tubule and not exclusively in the initial portion as previously reported.

Animals↗

Scanning electron microscopy of renal vascular casts.

The use of Cementex to form casts of the renal vascular system is described. These casts are useful in delineating the vascular microarchitecture of the kidney including that of the glomerular capillaries, but do not appear to reproducibly reflect physiological vascular tone. The postglomerular vascular system is often incompletely filled using this technique. The amount of filling can be altered by the techniques used in cast preparation. The effect of perfusion pressure, concentration of Cementex, fixation, and type of colour additive are compared with respect to the cast structure.

Animals↗

Scanning and transmission electron microscopy of mercuric chloride-induced acute tubular necrosis in rat kidney.

Scanning (SEM) and transmission (TEM) electron microscopy were used to elucidate morphological changes associated with acute tubular necrosis induced by high doses of mercuric chloride. Marked morphological changes were demonstrated in proximal tubules with TEM at one hour and with both SEM and TEM at six hours. These changes appeared earlier than reported in previous studies using any dose. The scanning microscopic provided a three-dimensional view of proximal cells showing changes in early injury with subsequent separation of the injured cells from the remaining cells. Certain of these residual cells change into low-lying cells with reline the proximal tubule. Variability was seen in the number of residual cells. However, once cell injury was initiated, necrosis proceeded in a reproducible manner.

Acute Kidney Injury↗

Scanning and transmission EM of rat kidney following low dose mercuric chloride administration.

The development of necrosis and the subsequent regeneration of the proximal tubular epithelium located in the cortex and the outer medulla of the rat kidney following subcutaneous injection of 2 mg of mercuric chloride per kilogram of body weight was observed utilizing light micromicroscopy (LM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The cortical proximal tubules were largely free of injury. In the medullary proximal tubules, the residual, undamaged cells underwent a change in phenotype appearance involving loss of the microvillus border, a decrease in cell height, and an increase in cytoplasmic ribosomes. These cells phagocytosed luminal debris. With time the cell height gradually increased, specialized organelles returned, and the luminal microvilli progressed from short, sparse profiles, to tufts of longer microvilli and finally the brush border was completely reformed. Some kidneys contained calcified tubules which regenerated more slowly than damaged but uncalcified tubules. Similarly, the medullary segments of the proximal tubules regenerated more slowly than the juxtamedullary region. Clusters of epithelial cells were occasionally seen growing into the tubular lumina during regeneration. Marked intersitial leukocyte infiltrations were observed.

Acute Kidney Injury↗

Alterations of the renal papilla during mercuric chloride-induced acute tubular necrosis.

Marked morphologic changes were seen in all structural elements of the renal papilla during mercuric chloride-induced acute tubular necrosis. Expect for the descriptions of increased numbers of leukocytes within the medullary vasa recta, papillary changes have not been described previously. The techniques used in this study included light microscopy, scanning electron microscopy, and transmission electron microscopy. The renal interstitial cells developed an extremely irregular contour and were penetrated by large irregular cavelike structures. A marked decrease occurred in the size and number of the cytoplasmic lipid droplets in these cells. The volume of the Golgi area, and of the rough and smooth endoplasmic reticulum increased. The morphologic changes in the renal interstitial cells were indicative of increased activity rather than of cellular injury. This is of insterest because several investigators have postulated that the interstitial cells are the site of renal prostaglandin synthesis Incrreased prostaglandin synthesis and release have been proposed to play a role in the redistribution of renal blood flow seen during acute renal failure.

Acute Kidney Injury↗