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11.
C S Aaron L F Stankowski P R Harbach R Valencia J K Mayo J Mirsalis J H Mazurek K L Steinmetz S K Wiser D M Zimmer 《Mutation research》1989,223(2):111-120
U-48753E is a potential human drug which was subjected to a battery of short-term assays for genetic activity. The compound was negative in the Salmonella (Ames) test, the in vitro UDS assay, the mouse bone-marrow micronucleus test and the Drosophila sex-linked recessive lethal assay. However, it was weakly positive in the CHO/HPRT assay in the presence of metabolic activation (S9). The weak positive response might easily have been labeled artifactual since there was no dose response and the dose level producing positive findings varied from experiment to experiment. In addition, the weak positive response was not confirmed in V79 cells. However, a reproducible dose-related increase in mutants was observed in the AS52/XPRT assay in the presence of S9. Metabolism of this drug proceeds through conversion of aliphatic N-methyl groups to formaldehyde. Addition of formaldehyde dehydrogenase to the S9 resulted in elimination of the mutagenicity of the compound in AS52 cells. Thus, the mutants were probably induced by formaldehyde. From the endogenous levels of formaldehyde in human blood, and the limiting potential therapeutic dose levels, the genotoxic hazard associated with U-48753E is marginal. This assessment of risk and its quantitation depend upon an understanding metabolism and exposure limits imposed by known side effects of the drug. This study can serve as a model for quantitative genetic risk assessment when mutagenicity is due to N-demethylation and formation of formaldehyde in situ. 相似文献
12.
The in vitro unscheduled DNA synthesis assay (UDS) is part of the routine genetic toxicology screening at The Upjohn Company. The purpose of this paper is to report results for 8 compounds which were tested in the in-house genetic toxicology program. These compounds represent diverse chemical structure and most of them entered the screening program because they are biologically active in efficacy screens. All tests were carried out under Good Laboratory Practices Regulations of the U.S. Food and Drug Administration. None of the materials reported here produced an increase in UDS and therefore the UDS results with these compounds do not suggest potential for genotoxicity. 相似文献
13.
Dr. Stefan B. Cajander M. P. Hugin Peter Kristensen Aaron J. W. Hsueh 《Cell and tissue research》1989,257(1):1-8
Summary The observation that tissue-type plasminogen activator (tPA) activity increased dramatically in preovulatory follicles has led to the hypothesis that plasminogen activation is causally related to follicle rupture. With immunohistochemistry, we have studied the appearance of tPA in ovaries of immature rats induced to ovulate and in adult cycling rats. Treatment of immature female rats with a single dose of pregnant mare serum gonadotropin (PMSG) induced follicular maturation. A subsequent human chorionic gonadotropin (hCG) injection resulted in follicle rupture 12–14 h later. PMSG treatment alone did not induce appearance of tPA-immunoreactive cells in any ovarian compartment. After hCG stimulation, however, theca cells, granulosa cells, and oocytes of pre- and postovulatory follicles displayed distinct tPA immunoreactivity. Fibroblastlike cells in the theca layers and tunica albuginea of the follicle apex also demonstrated localized cytoplasmic tPA reactivity. In addition to tPA synthesis in preovulatory follicles, hCG also induced tPA staining in the theca (but not granulosa) layers of non-ovulatory follicles. At 24 h after hCG treatment, there was a marked tPA staining in developing corpora lutea, ovulated ova, and oviductal epithelium. Ovaries from regularly cycling adult rats displayed a similar ovulation-related pattern of tPA immunostaining. The appearance of tPA in different cell types of the preovulatory follicle and in the fibroblast-like cells at the follicle apex, strengthens the hypothesis of a direct involvement of tPA in follicle rupture. Presence of tPA in postovulatory oocytes, cumulus cells, and surrounding oviductal epithelium may also indicate a role for tPA in the transfer of eggs in the oviduct.This work was supported by NIH Research Grants HD-14084; 12303 相似文献
14.
Synopsis New information regarding the ecology ofScytalina cerdale was obtained over a four year period as a consequence of a long-term marine ecological study at the Diablo Canyon Power Plant (DCPP), San Luis Obispo County, California. Twenty intertidal fish surveys were conducted at approximately quarterly intervals, between March 1979 and June 1983, at three separate rocky shore locations (stations). During each survey, a total of 108 square meters (36 m2 per station) was searched for fish during periods of low tide. A total of 280S. cerdale were collected, identified, measured, and released back into the same 4 m2 area, from the same intertidal station (Diablo Cove), throughout the study period. This limited intertidal occurrence most likely reflectsS. cerdale microhabitat requirements; a combination of intertidal elevation (mean = +0.3 MLLW), substratum specificity (loose gravel, 5–10mm size range, overlying a base of sand and shell fragments), and degree of wave exposure (semi-protected). Throughout the study,S. cerdale was seasonally more abundant during summer months (June through August) and less abundant during winter months (November through February). The only exception to this abundance trend followed the 1982 winter storms, which coincided with an El Niño event, whenS. cerdale abundance uncharacteristically dropped during the subsequent 1983 spring and summer surveys. Mean total lengths did not vary greatly, reflecting the absence of early juvenile fishes, and relatively high mean fish densities (3.5 fish per m2 for 20 surveys) were recorded. Qualitative comparisons betweenS. cerdale abundance and seasonal changes in water temperature indicated an inverse relationship. Gravid females, demersal egg masses, and early juvenile individuals were never observed during the four years of the study. This suggests that unlike most other intertidal fishes, particularly other blennioids,S. cerdale may not utilize the intertidal zone for reproductive and recruitment purposes; Diablo Canyon is the most southerly reported distribution for this intertidal species, and therefore, may not entirely represent the species' biology as a whole. 相似文献
15.
The Intracellular Localization of Hormonal Activity in Transplantable Thyrotropin-Secreting Pituitary Tumors in Mice 总被引:1,自引:0,他引:1
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Virendra B. Kamat Donald F. Hoelzl Wallach John F. Crigler Jr. Aaron J. Ladman 《The Journal of cell biology》1960,7(2):219-226
Mouse pituitary tumors secreting almost exclusively thyroid stimulating hormone have been characterized electron microscopically. Tumors of known thyrotropin content were separated into nuclear, mitochondrial, microsomal, and soluble fractions by differential centrifugation. The hormonal activity of these fractions was correlated with that of the total homogenates and with their nitrogen and phosphorus content. Essentially all the thyrotropin of the homogenate was recovered in a particulate fraction sedimenting between 20,000 and 40,000 g. This fraction contained the RNA granules and membranous components typical of microsomal pellets, but also showed the presence of small dense bodies surrounded by smooth membranes. These bodies were also visible within the endoplasmic reticulum of intact cells, and it is postulated that these bodies may represent the sites of intracellular elaboration and/or storage of TSH. Thyrotropin is tightly associated with microsomal particles but can be brought into solution by treatment with alkaline media, deoxycholate, and certain organic solvents. 相似文献
16.
17.
Paget's disease has been ascribed several times to specimens of archeological bone but, in the absence of microscopic examination, the evidence remains insubstantial. Suspected metabolic bone disease is described here in the archeological remains of a skeleton from a 16th century burial ground at Wells Cathedral, England and from a single medieval sacrum recovered from a large deposit of disarticulated bones from a churchyard at Barton-on-Humber, England. Radiographs showed apparent structural abnormality in one femoral shaft and calcaneus and in the isolated sacrum. Histomorphometry on undecalcified bone cores confirmed the regions of abnormality and showed not only increased trabecular width but also areas of "mosaic" woven bone together with extensive resorption cavities; these features contrasted with the normal structure and organized lamellar bone from sites elsewhere. Despite post-interment changes in surrounding tissues, the morphological stability of some of the osteocytes was remarkable. Preservation of the histology was sufficient to permit the assignment of a metabolic bone disorder and the nature of the sclerosis was consistent with Paget's disease. 相似文献
18.
Hurricane Danny resulted in the rapid deposition of 10cm of oxidized, acidic sediment in the Contrary Creek arm of Lake Anna, Virginia. Several biological and geochemical parameters were monitored with time to ascertain how long it took the newly-deposited lake sediments to attain the anaerobic, circumneutral, actively sulfate-reducing state normally observed in this portion of the lake. The sediment platinum-electrode potential dropped from 350 mV to 100 mV within the first week after the storm. The pH of the pore water increased from 4.5 to 5.8 within three weeks, and titratable alkalinity was detected within two weeks and three weeks at 3 cm and 1 cm depths, respectively. Accumulation of reduced products of sulfate reduction (acid volatile sulfide) began by three to four weeks after the storm event. Both methanogens and sulfate reducers were present in high and approximately equal numbers in the freshly deposited material. The rapid neutralization of the acidity in the fresh sediment prior to the onset of sulfate reduction suggests that reactions other than sulfate reduction caused the initial increase in pH and alkalinity in this system. 相似文献
19.
The nervous system of Tricladida. I. Neuroanatomy ofProcerodes littoralis (Maricola,Procerodidae): An immunocytochemical study 总被引:3,自引:0,他引:3
Maria Reuter Margaretha K. S. Gustafsson Cecilia Sahlgren David W. Halton Aaron G. Maule Chris Shaw 《Invertebrate neuroscience : IN》1995,1(2):113-122
The organization of the nervous system ofProcerodes littoralis (Tricladida, Maricola, Procerodidae) was studied by immunocytochemistry, using antibodies to authentic flatworm neuropeptide
F (NPF) (Moniezia expansa). Compared to earlier investigations of the neuroanatomy of tricladid flatworms, the pattern of NPF immunoreactivity inProcerodes littoralis reveals differences in the following respects: 1. Shape and structure of the brain. 2. Number and composition of longitudinal
nerve cords. 3. Shape of branches of, and transverse connections between, main ventral nerve cords. 4. Composition of the
pharyngeal nervous system. The rich innervation by NPF immunoreactive (IR) fibres and cells of the subepithelial muscle layer,
the pharynx musculature and the musculature of the male copulatory apparatus indicates a neurotransmitter or neuromodulatory
influence on muscular activity. 相似文献
20.
The nervous system of Tricladida. II. Neuroanatomy ofDugesia tigrina (Paludicola,Dugesiidae): An immunocytochemical study 总被引:2,自引:0,他引:2