Nuclear Clumps Research Articles

Effect of hyaluronidase during the early phase of acute myocardial ischemia: An ultrastructural and morphometric analysis

Hyaluronidase has been shown to reduce the size of experimental myocardial infarcts and to prevent the reduction in collateral coronary blood flow that normally occurs 15 minutes to 6 hours after coronary occlusion. To study the mechanism of action of this agent further, its effects on cardiac ultrastructure during the early phases of myocardial ischemia in the rat were examined. The left coronary artery was ligated for 1 or 3 hours in untreated and hyaluronidase-treated rats and tissue was sampled for electron microscopy. Morphometric analysis, using light microscopy on 1 μ thick specimens of tissue taken from comparable anatomic sites of the ischemic anterior left ventricular wall 3 hours after occlusion, showed that in the untreated rats 80 ± 7 percent (mean ± standard error) of myocardial cells and 48 ± 8 percent of vessels had morphologic evidence of ischemic damage, whereas in treated rats 50 ± 10 percent of myocardial cells ( P < 0.05) and 24 ± 6 percent ( P < 0.05) of vessels had ischemic changes. Ultrastructural studies of untreated ischemic tissue at 1 hour showed absence of glycogen, nuclear chromatin clumping, intermyofibrillar edema, I bands, intramitochondrial dense bodies and edema, endothelial blebs, gaps and swelling and decreased pinocytotic vesicles, red cell sludging and microscopic foci of hemorrhage. At 3 hours myocardial cell and vascular damage were more severe. In treated animals, more myocardial and endothelial cells from the ischemic anterior ventricular wall appeared normal on electron microscopy at both times. In these animals, myocardial cells that showed ischemic damage had nuclear, mitochondrial and myofibrillar morphologic features similar to those of untreated rats, but more glycogen granules were present than in the untreated group. Hyaluronidase may protect ischemic myocardium by preserving glycogen, and its preservation of collateral flow may be related to its reduction of ischemic damage in the microvasculature.

Aminophylline-induced preictal alterations in cortical astrocytes

A light and electron microscopic study was performed on rat cerebral cortex in the preictal state following the intraperitoneal injection of aminophylline. Morphological changes were observed only in astrocytes. The changes consisted chiefly of nuclear and cytoplasmic hydropic alterations, nuclear chromatin clumping, and a slight increase in cytoplasmic glycogen. It is suggested that astrocyte abnormalities may play a role in the pathogenesis of aminophylline-induced seizures.

Plasmodium berghei: Osmotic fragility of malaria parasites and mouse host erythrocytes

The osmotic properties of intraerythrocytic and ultrasonically liberated malaria parasites ( Plasmodium berghei) were analyzed and compared with those of mouse host erythrocytes utilizing a multiple tube fragility test. Cells were incubated in phosphate buffered saline solutions of varying osmolalities ranging from 20–4000 mOsm. Changes in cell ultrastructure and parasite infectivity were used as indicators of osmotic damage. Intraerythrocytic and host cell-free plasmodia showed similar patterns of cell alteration and changes in infectivity following osmotic stress. The various developmental forms within each of the preparations responded somewhat differently to hypo-osmotic stress, however. The majority of merozoites seemed to be more sensitive than many trophozoites, schizonts, and segmenters. Small trophozoites were, on the average, more resistant than other developmental forms. Incubation of parasite populations in hypotonic salt solutions with osmolalities slightly greater than the infectivity threshold of 100 mOsm lysed the majority of the merozoites, whereas many small trophozoites were still intact. While normal erythrocytes were more resistant to hypo-osmotic stress than were either intracellular or free parasites, the majority of parasitized erythrocytes was less resistant than normal erythrocytes. The predominant alteration induced by hyperosmotic stress appears in the parasite's nuclear region with myelination of the nuclear membranes and chromatin clumping. The infectivity threshold in the hypertonic range was found to be approximately 2500 mOsm. Results indicate that these obligate intracellular parasites have a wide range of osmotic sensitivities and that they are capable of existing for short periods in various osmotic environments ranging from 100–2500 mOsm without complete loss of infectivity. This suggests that these parasites have osmotic regulatory capabilities at least comparable to those of host cells.

Mitotic cell death and delay of mitotic activity in guinea-pig embryos following brief maternal hyperthermia

ABSTRACTPregnant guinea-pigs were exposed to an environmental temperature of 42·0–42·5 °C for 1 h on day 21 of gestation. Their embryos were removed at periods from 45 min of heating to 48 h following exposure. Histological preparations of embryos showed clumping of nuclear chromatin and subsequent death of cells which were at about the stage of mitosis. Affected cells were particularly numerous in the central nervous system. Further mitotic activity was inhibited for 6–8 h. Squash preparations of the telencephalon at 1 h after heating showed an increase from 3 to 86 % in the number of mitotic cells showing damage in the form of nuclear clumping; this number fell progressively to 30% by 24 h after heating. The proportion of cells in various stages of mitosis changed considerably at 1–8 h after heating, but had returned to pre-heating values by 24 h. The proportion of cells in prophase fell markedly, while the proportion of metaphase cells was doubled at 4 h after heating, indicating blocks to the cell generation cycle before prophase and in metaphase.

The influence of a prenatal trauma on formation of Purkinje cells.

AbstractThe first goal of this investigation was to determine the time of origin of Purkinje cells and their final location in the various lobes of the cerebellum. DUB/ICR mice were therefore injected with several doses of 3H‐thymidine on day 11, 12, 13, 14, or 15 of gestation. Cells formed on days 11 and 12 appeared in all lobes of the postnatal vermis but those formed on day 13 became located mainly in the anterior lobe.The second goal was to examine the effect of 5‐fluorodeoxyuridine, a DNA synthesis inhibitor, on Purkinje cell formation and on repair of the rhombic lip after a prenatal trauma. Five hours after treatment with fluorodeoxyuridine cells with darkly stained nuclear clumps appeared and mitotic activity ceased. Twelve hours after treatment mitotic activity remained low and more affected cells appeared in the neuroepithelium of the rhombic lip. By 24 hours abnormal cells had disappeared, mitotic activity was almost normal and the neuroepithelium had regained its regular continuity. Treatment on day 12 led to a significant deficit of Purkinje cells in all lobes of the vermis, while treatment on day 13 caused a deficit in the anterior lobe only. Despite the postnatal Purkinje cell deficit, compensatory cell proliferation had occurred in the rhombic lip. The mitotic index in the treated embryos reached the value of the controls after 24 hours and was extremely high after 48 hours. Part of this proliferative activity leads to Purkinje cell production, for it was possible to label substantial numbers of Purkinje cells on day 14 of gestation in animals treated with fluorodeoxyuridine on day 12, while control animals have virtually completed Purkinje cell formation by day 14. Although Purkinje cell deficits were accompanied by a reduction in the size of the cerebellum, the cytoarchitecture of the cerebellum appeared normal.

An electron microscopic study of macroglia and microglia in the lateral funiculus of the developing spinal cord in the fetal monkey.

An electron-microscopic study has been made of the glial cells in the developing lateral funiculus of the cervical spinal cord in fetal rhesus monkeys. The various macroglial cell types, their precursor cells, and microglia are discussed in detail. An astrocytic lineage is proposed in which glioblasts present in the lateral funiculus give rise to astroblasts that then develop into mature astrocytes. Oligoblasts apparently migrate into the lateral funiculus as such and develop into active oligocytes. The active oligocytes become most predominant during the initial stages of myelinogenesis and are in direct continuity with developing myelin. The active oligocytes develop into mature oligocytes after myelination is completed. Microglia cells are present throughout development as three forms; resting microglia, globose microglia, and active microglia. The globose and active microglia predominates at specific times early in development when degeneration of apparent neuronal processes is taking place. The microglia cells are characterized by dense nuclear chromatin clumps, lipid inclusion bodies, dense vesicles, and, often, intracellular debris.