Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transplacental exposure to the DNA alkylating agent N-methyl-N-nitrosourea on day 16 of gestation in CD-1 albino mice induces a degeneration of the retina, the severity of which depends upon the dosage level of the drug. A 1 mg kg-1 dose provokes a progressive retinal degeneration in the offspring which begins at about 4-6 weeks of age and is characterized by gradual thinning of the retinal layers. A 15 mg kg-1 dosage of MNU provokes severe retinal dysplasia characterized morphologically by rosettes in the outer nuclear layer and loss of rod outer segments (ROS). In the present biochemical experiments, retinal protein synthesis was examined in mice 2-, 4-, and 6 weeks of age exposed to 1 mg kg-1 MNU and 2- and 5 weeks of age exposed to 15 mg kg-1 MNU. Phospholipid synthesis was examined in mice 2-, 4-, 6- and 12 weeks of age exposed to 1 mg kg-1 MNU and at 2 weeks in mice exposed to 15 mg kg-1 MNU. Retinas were incubated for 2 hr at 37 degrees C in media supplemented with either [3H]leucine for protein synthesis studies or [3H]glycerol for phospholipid synthesis experiments. Aliquots of crude ROS and the retinal debris were taken for protein determination, scintillation counting, SDS-PAGE separation of labeled opsin, phosphorus determination and TLC separation of phospholipids. Results indicated that mice exposed to 1 mg kg-1 MNU did not differ significantly from age-matched controls in these measurements, whereas mice exposed to 15 mg kg-1 MNU were significantly different from controls. These results suggest that even as early as 2 weeks of age protein and lipid metabolism are adversely affected in mice exposed to the higher dose of the alkylating agent at a critical time in retinal development, but general protein and lipid synthesis is not affected in animals exposed to 1 mg kg-1 MNU at least up to 12 weeks of age. These studies suggest further investigation of more subtle derangement in the retinal function in animals exposed to low levels of MNU.
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PMID:Biochemical characterization of retinal protein and phospholipid synthesis in mice exposed transplacentally to N-methyl-N-nitrosourea. 319 72

In this investigation skin fold thinning was determined after topical application of several potent corticosteroids in hairless mice using a simple mechanical measuring device. The skin thinning effect of prednicarbate was compared with other corticosteroids (amcinonide, beta-methasone-17-valerate, clobetasol-17-propionate, diflorasone-17,21-diacetate, hydrocortisone-21-acetate). Prednicarbate produced a clear thinning of skin. Like other tested dermatocorticoids prednicarbate caused a significant atrophy of the mouse tail epidermis. By prednicarbate the 3H-thymidine triphosphate incorporation into epidermal DNA was inhibited.
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PMID:Investigation of the skin thinning effect of prednicarbate and other corticoids in mouse skin. 327 51

Although the redox cycling of paraquat (PQ) and the resultant "activated oxygen" generation are important in toxicity development, the intracellular events leading to cell injury remain unclear. To understand the mechanism of PQ-induced cell injury, we have studied the effects of PQ on DNA synthesis, cell proliferation, the cytoskeletal organization, particularly microtubules (MT) and microfilaments (MF), and the synthesis and composition of cytoskeletal proteins in mouse 3T3 cells. PQ treatment produced a dose-dependent inhibition of DNA synthesis and cell growth. Exposure of cells to PQ (313 microM, 20 hr) resulted in MT aggregation and bundling as well as MF redistribution in the perinuclear area as revealed by fluorescence microscopy. Although this PQ dose inhibited DNA synthesis by 95%, it caused only a 22% decrease in protein synthesis of the cytoskeletal fraction. Higher doses of PQ (1250 microM, 20 hr) caused (a) dramatic thinning out and loss of MT and (b) marked loss of MF cables and the appearance of numerous pine needle-like structures much finer and shorter than normal MF. Under these conditions, the synthesis of cytoskeletal proteins was decreased by about 83%. Further analysis of the cytoskeletal fraction from PQ-treated cells by sodium dodecyl sulfate gel electrophoresis showed (a) that tubulin was greatly diminished, in agreement with microscopic observations; (b) that two new protein bands appeared; and (c) another protein band which was also reduced considerably. These results indicate that the PQ-induced dose-dependent cytoskeletal injury may be important to the mechanism of cytotoxicity of this herbicide.
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PMID:Paraquat-induced cytoskeletal injury in cultured cells. 367 19

A model of retinal degeneration has been developed in mice which is induced by the DNA alkylating agent methylnitrosourea. Pregnant mice were injected with various doses of this potent teratogen on day 16 of gestation, a time of differentiation of numerous cell types of the mouse retina. Histological examination of retinas from offspring exposed to 20-, 10- and 5 mg kg-1 doses demonstrated retinal rosettes, a pathology similar to retinal dysplasia. The 1 mg kg-1 dosage did not produce rosettes; in fact, retinas appeared morphologically normal early in life. Control and treated animals were studied at specific age intervals: 2-, 4-, 6-, 8-, 12-, 16-, 20-, 36-, 52 weeks. Measurements of the overall retinal width and five retinal layers were made to quantify the degeneration. Results indicate a thinning of the retina begins at 4 weeks and worsens with age. These results are discussed with respect to the potential of low-level exposure to environmental toxins as a possible cause of retinal degeneration.
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PMID:Retinal degeneration in the mouse. A model induced transplacentally by methylnitrosourea. 380 63

The spontaneous removal of substances from the eye in vivo and histopathological responses to mild or moderate irritants were examined to define the main features that may be reflected in a valid in vitro test for irritant potential. Solutions or fine particulate suspensions applied to the rabbit eye are quickly removed from the central corneal surface by the blink reflex, gravity and drainage. The histological changes in the first 24 hours of mild-to-moderate irritation show some thinning of, but no severe irreversible damage to, the corneal epithelium. Other changes are oedema, congestion, some leucocyte infiltration and variable degeneration and desquamation of the conjunctival epithelium. In vitro cell-culture cytotoxicity tests are a useful screen for direct cytotoxic damage to epithelial cells but there are anomalies between the results of such tests and in vivo eye responses. Test systems using inhibition of DNA synthesis in cultured fibroblasts and histamine release from mast cells have shown poor correlation between in vitro and in vivo test results. The in vitro corneal injury (eye organ) test of Burton et al. (Fd Cosmet. Toxicol. 1981, 19,471) predicts very effectively the activity of moderate-to-severe irritants, and that of mild irritants when the contact time is modified or fluorescein or histology are used. This method demonstrates the response of a specialized tissue of the eye and facilitates the examination of powders, acids and alkalies, for which cell systems are not suitable. So far the chorioallantoic membrane of the egg has not been found to predict for pure chemicals the activities demonstrated in in vivo or in vitro tests on the eye; the main change seen in the egg membrane is necrosis, with little evidence of inflammation.
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PMID:Ability of in vitro (corneal injury--eye organ--and chorioallantoic membrane) tests to represent histopathological features of acute eye inflammation. 387 30

The Eastern pipistrelle (Pipistrellus subflavus) is typical of exceptionally small bats capable of a 30-fold range in aerobic metabolism as they arouse from hypothermia and sustain foraging flight. This report describes their basic lung structure and the extent to which this organ is protected from protein depletion during hibernation. Bats were collected at the beginning (Fall), middle (Winter), and end (Spring) of hibernation from a permanent overwintering cave, and analyzed within several days of capture. Regardless of whether bats were examined in the Fall (average body weight = 6.22 g) or in the Spring (4.58 g) no significant differences existed for total lung volume (237 microliter), alveolar surface area (338 cm2), harmonic mean septal thickness, tau ht (0.221 micron), or membrane diffusing capacity (4.13 microliter O2/sec/mbar). These parameters exceed predictions based on body weights for either season, and resemble published data for another highly active mammalian group, the insectivorous shrews. Both tau ht and the minimal septal thickness of 0.083 micron approach the anatomical limits for thinning of alveolar septa without loss of epithelial continuity. Although both the heart and lungs lost 13% of their fresh weights during hibernation, compared to 25% for the liver, the lung contents of DNA (0.14 mg) and blood-free protein (7.38 mg) were not altered significantly. These small bats possess lungs which are well suited for the high aerobic cost of flight. Those lungs are resistant to hibernation-induced proteolysis, and also resistant to the deterioration of alveolar membranes which occurs in nonhibernators subjected to starvation-induced weight losses of similar magnitude.
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PMID:Pulmonary design in a microchiropteran bat (Pipistrellus subflavus) during hibernation. 399 64

The response of mouse ear epidermal transglutaminase to single applications of anthralin, retinoic acid (both 59 micrograms/ear) or fluocinolone acetonide (2 micrograms/ear) was determined. Anthralin and retinoic acid caused inflammation and accumulation of epidermal protein and DNA, whereas fluocinolone acetonide resulted in ear thinning and decreased epidermal protein and DNA. Treatment with either anthralin or retinoic acid caused increases in absolute amounts of epidermal transglutaminase activity/ear. Anthralin increased this parameter 70-100% above acetone-treated controls from 48 hr through 7 days. Retinoic acid-treated ears showed a slower initial increase but peaked at 4 times control level by 96 hr before returning to normal at 7 days. Fluocinolone acetonide treatment had no effect on this parameter. The specific activity of epidermal transglutaminase (total epidermal transglutaminase/total soluble epidermal protein) was decreased by retinoic acid treatment; was maintained at normal levels by anthralin (except for the 7-day point where it decreased 50%); and was dramatically stimulated by fluocinolone acetonide. In the latter case, specific activity was more than 5 x control by 96 hr and still near this level at 7 days. Epidermal transglutaminase activity is a marker of differentiation, and protein and DNA accumulation an indication of growth. Thus, at the doses studied, retinoic acid favors growth over differentiation, anthralin maintains a normal to near normal ratio of growth to differentiation, and fluocinolone acetonide strongly favors differentiation over growth.
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PMID:The effect of topical drugs on mouse ear epidermal transglutaminase activity. 612 46

Congenital angular deformity of the tibia (CADT) is one of the classic inborn errors. The treatment of the disease is very difficult because of insufficient clinical and experimental data and lack of complete experimental model of the disease. The present study is designed to establish a new experimental model of CADT. In vivo experiment: Only one injection of ethane-1-hydroxy-1,1-diphosphonate (EHDP) (4 X 10(-2)-4 X 10(-1) mumol/g egg wt.) was given into the yolk sac of fertile white leghorn egg at 8 days of incubation. The skeletal deformities of the chick embryos were examined during the period of EHDP-administration until hatching. Furthermore, the effect of EHDP was compared with that of its analogs (dichloromethylene diphosphonate: Cl2MDP and inorganic pyrophosphate: PPi) in a similar manner. In vitro experiment: Tibiae from 9-day-old chick embryos were cultured at 37 degrees C for 6 days by roller-tube method in the medium containing EHDP, Cl2MDP or PPi at concentrations of 4-400 microM to measure dry weight and calcium content of the tibiae. The results are summarized as follows. Angular deformity of the tibia in chick embryo was produced in vivo specifically by EHDP-administration compared to its analogs. There existed the critical stage of bone development and the critical dose of EHDP-administration to induce angular deformity of the tibia. The incidence and the severity of the tibial bowing depended on the dose of EHDP-administration. The thinning of periosteal bone collar and retardation of primary bone marrow formation were observed in EHDP-administered tibia. According to 3H-thymidine autoradiographic study, EHDP inhibited DNA synthesis of osteoblast by about 58% after 2 days of administration. The DNA synthesis of chondrocyte was also inhibited by about 20% after 2 days of EHDP-administration. EHDP had a more inhibitory effect on calcification of chick embryonic tibiae than Cl2MDP and PPi at concentration of 40 microM without influencing the dry weight of tibiae in vitro. This new experimental model of CADT offers a significant possibility to elucidate the etiology of this disease.
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PMID:[Congenital angular deformity of the tibia in chick embryo induced by ethane-1-hydroxy-1, 1-diphosphonate (EHDP)]. 644 26

Corneas of fetal and young albino rabbits were examined by light and transmission electron microscopy. In addition, DNA and hydroxyproline content were measured in developing stroma. The results were compared with similar data from healing corneas in adult rabbits and from developing corneas of other animal species. In the fetal rabbit, the prospective corneal stroma region contains an unorganized, sparse extracellular matrix until about the 13th day of gestation, when mesenchymal cells and capillaries from the hyaloid vessels move in to form the vascular pupillary membrane, endothelium, and stroma. Stromal growth is due to alteration in the density and morphology of the cell population early in development, along with a sequential thickening and thinning of the whole stroma. These events are similar to those reported in primates, but differ markedly from those reported in avian species. Normal developing cornea and healing adult cornea both involve migration of stomal fibroblasts and deposition of extracellular matrix. Stromal fibroblasts in the rabbit fetus are oriented with their long axis parallel to the corneal surface early in development compared with randomly oriented fibroblasts in the early healing wound of adult rabbit corneas. Although collagen and cell number progressively increase throughout the developmental periods studied, the ratio of cells to collagen is high initially but decreases with development. In contrast, the proportion of cells to collagen in the young scar tissue of adult cornea is low initially, indicating a marked deposition of collagen in comparison to that in the early normal developing stroma. The results suggest that the healing tissue differs from the normal fetal stroma in its coordination of cell population growth with collagen deposition and cellular organization.
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PMID:Morphogenesis of rabbit corneal stroma. 684 Oct

The lindane embryotoxicity and associated changes in cysteine (CYS) and glutathione (GSH) status have been investigated in the early organogenesis-stage rat conceptus utilizing whole embryo culture techniques. Direct exposure of gestational day 10 (GD 10) conceptuses to lindane (50, 100, 200, 300, and 400 microM) in the culture medium resulted in a dose- and time-dependent increase in mortality (88% at 400 microM), frequency, and severity of malformations and in decreased growth parameters. Protein and DNA contents of embryo and visceral yolk sac (VYS), likewise decreased significantly as lindane concentrations increased. Lindane exposures greater than 100 microM produced abnormal axial rotation, pooled blood on lateral cephalic surfaces, cephalic edema, and decreased VYS vasculature. Histologic sections showed a variety of abnormalities, including distended anterior cardinal veins, thinning of the neuroepithelium in forebrain and hindbrain regions, and abnormal branchial arch development. CYS and GSH levels in the VYS were not significantly affected by 100 microM lindane exposure during a 5-h incubation period on GD 10 and GD 11. In contrast, CYS and GSH levels in lindane-exposed embryos remained unchanged while control levels continued to increase with gestational age. At 5 h, treated embryos showed a significant depletion of CYS (GD 10, 22%; GD 11, 35%) and GSH (GD 10, 41%; GD 11, 24%) relative to controls. Selective lindane-induced depletion of embryonic GSH suggests involvement of the glutathione redox cycle in lindane embryotoxicity.
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PMID:Lindane embryotoxicity and differential alteration of cysteine and glutathione levels in rat embryos and visceral yolk sacs. 752 28


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