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The ultrastructural pathology of the rat nervous system after chronic exposure to low levels of halothane was investigated. After 8 wk of exposure to 10 ppm halothane, collapse of the neuronal rough endoplasmic reticulum was observed. Dilatation of the Golgi complex and focal cytoplasmic vacuolation were observed within many cortical neurons. After exposure to 500 ppm halothane, vacuolation of the Golgi complex became even more severe. Membraneous degeneration of the neuronal mitochondria, intracellular edema of the glial cells, and necrosis of the cortical neurons could also be found. The present study indicates that halothane is neurotoxic and may be considered as an occupational hazard.

Sequential changes in liver cell morphology in mice infected with Coxsackievirus B3 have been studied using enzymic markers for early cell damage. Elevated alkaline phosphatase two days after infection was the only change identified consistent with the presence of virus in the tissue. Reduced glucose-6-phosphatase, and succinic dehydrogenase were associated with cytoplasmic vacuolation and fatty deposition which were clearly apparent 6 to 8 days after infection. Lysosomal acid phosphatase was increased at this stage in periportal areas and reduced in centrilobular regions. comparison of the Coxsackievirus induced changes with those induced by a direct liver pathogen—hepatitis virus, suggests that the histological and histochemical changes are probably of an indirect causation.

The proximal segment of the nymphal Malpighian tubules of tube-building cercopoids consists of two secretory zones, an anterior fibril zone and a posterior granule zone. Cytological changes in the latter are correlated with the production of spittle before each ecdysis. Granules are present in the cells during inter-ecdysal periods. Shortly before spittle-production and ecdysis, coalescence of the granules occurs, followed by cytoplasmic vacuolation and the subsequent liberation of coalesced material into the tubule lumen. The granule zone is essentially similar to the whole of the proximal segment of the Malpighian tubules of spittle-bug nymphs, although much smaller in length and cross-section. This is consistent with the reduced spittle-producing requirements of tube-building nymphs.

The effect of a dose of 450 roentgen on regenerating liver cells is to cause the disappearance of all alpha cytomembranes and glycogen. This loss is accompanied by complete cytoplasmic vacuolation. The cytoplasm remains vacuolated for about 9 to 10 hours after irradiation but after this new alpha cytomembranes and glycogen are formed. (auth)

Adult male mice were used to study the effect of Trenimon on the testis at light microscopical and ultrastructural level. Two groups under acute and prolonged experimental conditions respectively were studied. The first change observed was marked cytoplasmic vacuolation in Sertoli cells. In a later stage injured germinal cells, specially spermatocytes and spermatogonia, were scattered throughout the seminiferous epithelium and some phagocytized by the adjoining Sertoli cells, where the complete involution took place. A combined mechanism of Trenimon direct action on germ cells and a disturbance in the relationship Sertoli cell-germ could be suggested as the cause of germinal injury.

The effect of chloramphenicol on regenerating rat liver following partial hepatectomy has been investigated. High dosage regimes of chloramphenicol (600 mg/kg body wt every 6 h) were lethal to partially hepatectomized but not to normal rats. On lower dosage regimes (100–400 mg/kg body wt), chloramphenicol appeared to specifically inhibit the synthesis of the mitochondrial cytochromes a, a3, b and c1 in the actively growing liver tissue. In some of the liver cells there was extensive cytoplasmic vacuolation resulting from dilation of the endoplasmic reticulum, and the mitochondria were swollen and appeared to contain fewer cristae. It is suggested that chloramphenicol has at least three effects in the cells of higher organisms—a specific inhibitory effect on the synthesis of some mitochondrial cytochromes which is presumably a reflection of its action on the mitochondrial protein synthesizing system, an effect on cellular ultrastructure, and a direct inhibitory effect on cellular respiration only at relatively high concentrations of the drug. A number of previously described toxic effects of the drug on humans and other mammals are discussed in terms of the present observations.

Diagnosis was confirmed by the demonstration of cytoplasmic vacuolation and intranuclear inclusions in epithelial cells, and by observing the virus particles themselves by electron microscopy. Lesions persisted for at least 100 weeks.

1. Rats made hyperglycaemic by repeated intravenous injections of dehydroascorbic acid (DHA) were killed 24 hrs. (Group 1) and four days (Group 2) after the last DHA injection, and the pancreas, kidneys, liver, adrenals and thyroid were examined histologically. 2. The most marked lesions were found in the islets of Langerhans of the pancreas. In Group 1 animals there was degranulation and shrinkage of the β-cells, pyknosis of their nuclei, and occasionally vacuolation of their cytoplasm; rarely, actual disintegration of cells was observed. No glycogen was stainable in the β-cells. In Group 2 rats the islets were small: the β-cells were reduced in numbers, shrunken and usually agranular, with pyknotic nuclei. Cytoplasmic vacuolation was obvious, and though some glycogen was demonstrable in the cells, all the vacuolation could not be accounted for in this way. 3. The kidneys showed no significant degenerative change in either group, but there was some glycogen storage in the tubular cells of Group 2 rats. 4. In the adrenal cortices, a reduction of Sudanophil and Feulgenpositive material was observed in the zona glomerulosa and the zona fasciculata in the males of both groups, while no such change could be demonstrated in the females of Group 2. 5. No change of note was found in the livers or thyroids of the experimental animals. 6. The main lesions occurring as a result of injection of IDHA, those in the islets of Langerhans, are thus very similar to the lesions of experimental alloxan diabetes, but it appears that for comparable islet damage, DHA produces higher blood sugar concentrations.

The addition of 0.08 M sucrose to a culture medium containing Chang-strain human liver cells causes intense cytoplasmic vacuolation. Electron microscopy of these cells grown inferritin, time-lapse cinematography, and radioautography reveal that the vacuoles arise by endocytosis and that the sucrose is taken into the cell and localized in the vacuoles. Tracer studies demonstrate that sucrose-3H provides a marker for quantitation of endocytosis and that it neither induces nor stimulates endocytosis. Electron micrographs of vacuolated liver cells show microfilaments in close proximity to the inside of the plasma membrane, in the pseudopodia, and to the cytoplasmic side of the membrane surrounding endocytosis vacuoles. Cytochalasin B (CB), a mold metabolite that inhibits various types of cell motility, has a dose-dependent inhibitory effect on the uptake of sucrose-3H by these cells. This inhibition is accompanied by a cessation of the movement of ruffles and pseudopodia on the surface of the cells and the formation of blebs which arise from the cell's surface. These morphological changes are quickly reversible upon removal of CB. Alterations in the appearance and location of microfilaments are also observed in CB-treated cells.

A study of the fine structure of embryonic chick limb-bone rudiments in organ culture has shown that exposure to 0·08 M sucrose causes intense cytoplasmic vacuolation of the peripheral cells, while the structure of the cytoplasmic organelles is apparently unaltered. The lamellae and vesicles of the Golgi apparatus are more abundant than in the controls and the vesicles are no longer confined to the Golgi zone. The first vacuoles appear in the articular chondrocytes after exposure to sucrose and are autophagic vacuoles or clear vacuoles, probably containing sucrose. After 24 h or more the vacuoles are more heterogeneous and contain a great variety of membranous, granular and fibrous material. These vacuoles appear to be formed by fusion between endocytotic coated vesicles, autophagic vacuoles, multivesicular bodies, clear vacuoles and vesicles derived from the Golgi zone. After 2 days some vacuoles contain fibrils identical in appearance to those in the surrounding cartilage matrix. The development of vacuoles in the chondrocytes in the inner regions of the epiphyses is much slower and autophagic vacuoles are only seen after 6 days’ exposure to sucrose. Similar changes are observed in the fine structure of the perichondrial and periosteal fibroblasts, and after 2 days in the presence of sucrose many fibroblasts have cytoplasmic vacuoles containing banded fibres similar to the extracellular collagen fibres. In shafts of 11-day embryonic chicks exposed to sucrose for 8 days the cytoplasmic vacuoles in the osteoblasts contain banded fibres and dense crystallites resembling those of the bone matrix. When rudiments are transferred to normal medium after 2 days’ exposure to sucrose the vacuoles are gradually lost; some of the vacuoles appear to move to the periphery of the cell and then fuse with the plasma membrane, thus releasing their contents. Throughout this process the fine structure of the cytoplasmic organelles is unaltered. It is suggested that exposure to sucrose stimulates an increased production of lysosomal enzymes which are transported in small vesicles from the enlarged Golgi region to the clear vacuoles and to the autophagic vacuoles. It seems possible that during this process enzymes are released into the surrounding matrix and modify the ground substance sufficiently to enable some of the connective tissue cells to become actively phagocytic and to ingest collagen fibres and bone crystallites.

The acute effect on hematopoiesis of focal irradiation to bone marrow was evaluated by serial morphologic studies of aspirates from irradiated and from distant marrow sites during radiotherapy of 9 patients with cancer.In the irradiated marrow, the erythroid line showed marked reduction of early precursors at 400 r and complete disappearance of all nucleated cells at 1,000 r. The granulocytic line did not demonstrate marked reduction of early forms until 1,000 r had been delivered; giant granulocytes were most prominent at 1,000 r. Marrow lymphocytes were surprisingly persistent in the irradiated marrow; preservation of lymphocytic foci was noted in histologic sections of marrow at 2,000 r. Monocytes demonstrated cytoplasmic vacuolation at 400 r and tended to persist even at 2,000 r. Megakaryocytes were rarely noted after 1,000 r marrow irradiation. Histologic sections of marrow particles confirmed the hypocellularity of irradiated marrow. Plasma cells and reticular cells proved to be resistant to these d...

Lunar material collected during the Apollo 11, 12, 14, and 15 missions has been used to treat 12 species of higher plant tissue cultures. Biochemical and morphological studies have been conducted on several of these species. Tobacco tissue cultures treated with 0.22 g of lunar material exhibited increased greening more complex chloroplasts, less cytoplasmic vacuolation and greater vesiculation. Pine tissue cultures reacted to treatment by an increased deposition of tannin-like materials. The percentage of dry weight and soluble protein was increased in cultures treated with either lunar or terrestrial rock materials.

This paper describes the neural and extra-neural lesions seen in cattle, sheep and a horse associated with the ingestion of species ofSwainsona. The neural lesions consist of widespread watery cytoplasmic vacuolation of large neurones together with many spheroids (neuroaxonal dystrophy) and abnormal amounts of a lipofuscin-like pigment. Similar foamy vacuolation involves the choroid plexus, the exocrine panreatic parenchyma, the renal convoluted tubules and other viscera. The lymph nodes contain foamy macrophages in medullary sinusoids and/or much intracellular lipofuscin-like pigment.

Experimentally produced bovine cutaneous papillomas of 30, 76 and 112 days' duration as well as 3 naturally occurring bovine cutaneous papillomas were examined by light and electron microscopy. Degenerative changes were not observed in the fibromatous base of the 30-day-old papilloma. An alteration in all papillomas older than 30 days was cytoplasmic vacuolation in cells of the prickle cell and keratohyaline layers. As cells progressed upward their degeneration became more prominent. In the keratinized layers of 2 papillomas virus-like particles were observed within plasma membranes of keratinized cells.

Ingestion of 380 g per day of locoweed by pregnant ewes during day 40 to 72 of pregnancy results in vacuolation of the fetal membranes, specifically of the chorionic epithelium. These cells become hypertrophied and their cytoplasm severely vacuolated. It is postulated that this cytoplasmic vacuolation interferes with the transport of nutrients across the placental barrier. The vacuolating factor itself may, or may not, be associated with death of the conceptus and subsequent abortion. A contributing factor may be that luteal cells of the ovary are also extremely vacuolated in the ewes poisoned by locoweed and may not be producing sufficient progesterone to maintain pregnancy.

Lysosomal changes have been observed by histochemical methods in the BSC-1 green monkey kidney cell line and the 3T3 mouse cell line infected with high multiplicities of simian vacuolating virus (SV40) and in 3T3 cells infected with herpes simplex virus. BSC-1 cells infected with SV40 showed marked cytoplasmic vacuolation and lysis. The lysosomes were enlarged and aggregated and there was second-stage activation with release of enzyme into the cytoplasm. Possibly, some product of viral replication in the nucleus is released into the cytoplasm and brings about changes in lysosomes and other cytoplasmic organelles. Lysosomal enzymes probably contribute to the dissolution of cells and release of virus from nuclei. 3T3 cells infected with SV40 under these conditions do not lyse, but a large proportion may become transformed. First-stage activation of lysosomes was seen for at least 6 days. After 6 days these changes disappeared. The possible relationship of lysosomal changes to the events occurring in transformed cells is discussed. The cells infected with herpes simplex virus showed marked cytopathic effects associated with second-stage lysosomal activation.

The carotid bodies of a group of animals from high altitude were compared with those of a group from sea level. The carotid bodies from the high altitude group were larger and showed hyperplasia of the type I cells with cytoplasmic vacuolation. Electron microscopy revealed that this vacuolation was associated with changes in the membrane bound cytoplasmic bodies. It is suggested that the ultrastructural changes are related to the disturbance in chemoreceptor response found in subjects living at high altitude.

The amphibian virus, LT-1, produced relatively irregular necrotic areas in the monolayer of rainbow trout ovarian cells. The infected cells underwent the following cytopathic changes: extensive cytoplasmic vacuolation, formation of multiple nuclei, and paranuclear cytoplasmic inclusions.The site of replication of the virus in the infected rainbow trout ovarian cells was demonstrated to be located at the less electron-dense areas of the cytoplasm and surrounded by numerous vacuoles. A comparison of the susceptibility to LT-1 virus of rainbow trout ovarian cells with that of fathead minnow cells resulted in a calculated cytopathic index of 4.48.

Sheep experimentally poisoned by ingestion of Astragalus letiginosus developed cytoplasmic vacuolation of the proximal tubular epithelia within 4 days after beginning of the experiment. Neuronal vacuolation occurred by day 8 and had progressed to neuronolysis by day 16.

The addition of sucrose to a chemically denned culture medium caused intense cytoplasmic vacuolation of the perichondrial, oesteogenic and articular cartilage cells of limb-bone rudiments from day embryonic chicks grown in organ culture. The rest of the cartilage appeared unaffected by the sugar. The osteocytes were intensely vacuolated; the bone matrix was much less dense than that of the controls and had an abnormal fibrillar structure. When the explants were transferred to medium without sucrose, after 6 days vacuolation had almost disappeared. The effect of the sucrose was dose-dependent; at a concentration of 0·32M the sugar was highly toxic; at 0·16M the explants survived and vacuolation of the chondrocytes extended further into the cartilage than at 0·08M. A similar vacuolation of the cells in response to sucrose was seen in the isolated shafts of the limb-bones and in the mandibular rami from 11- to 13-day embryos; in the sucrose-treated explants osteogenesis was arrested and in places the bone showed osteolytic changes. In the absence of glucose, day limb-bone rudiments failed to grow and rapidly degenerated in medium containing 0·08 M sucrose, indicating that sucrose was very little if at all metabolized. Explants of day rudiments grown for 8 days in the presence of 0·08M glucose showed no vacuolation; dextran had some effect, and both mannitol and sorbitol caused vacuolation.

Cultivation of limb-bone rudiments in medium containing various non-metabolizable or poorly metabolizable sugars caused vacuolation of the perichondrial and articular cells and was accompanied by an increased synthesis and profuse secretion of lysosomal enzymes. Experiments with [14C]dextran indicated that the cytoplasmic vacuolation was due not to a higher rate of endocytosis, but rather to an abnormally long persistence of the pinocytotic vacuoles. Meta-chromatic material was lost from the cartilage only in the immediate vicinity of the vacuolated articular chondrocytes and the amount of hexosamine and hydroxyproline released into the medium was not much increased. However, the hexosamine and hydroxyproline of the sucrosetreated rudiments was much more susceptible to extraction with neutral salt than those of paired controls. Sucrose taken up by the cells was liberated when the rudiments were returned to normal medium; this release, unlike the secretion of lysosomal enzymes, was unaffected by the presence of hydrocortisone. It is probable that the primary lysosomes, formed in the enlarged Golgi region, are the vehicles for the secretion of lysosomal enzymes. No appreciable amount of enzymic activity was released into the medium from rudiments grown in the presence of 0·08 M sucrose, before 36 h; at, or just before this time, however, a net increase in synthesis of enzyme was observed. The role of endocytosis in the resorption of skeletal matrix is discussed.

The sequence of early cytopathic changes produced by vesicular stomatitis virus in fibroblastic or epithelial cell types were studied by phase contrast microscopy. The final stage of cytopathology, which was rounding of cells, was similar in both cell types. However, early changes peculiar to each of the cells were observed. For the fibroblastic cells it was pseudopodal budding of the cell membrane, while the epithelial cells showed cytoplasmic vacuolation. In both cell types there was apparent arrest of cell division at late telophase.