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  • 1990-1994  (38)
  • Apoptosis
  • English fiction., lcsh
  • English poetry., lcsh
  • 1
    ISSN: 1432-0533
    Schlagwort(e): Key words Amyotrophic lateral sclerosis ; LeY ; Nick-end labeling ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Expression of LeY, a difucosylated type 2 chain determinant, has been previously identified as a characteristic of cells undergoing apoptosis. Immunohistochemistry using an antibody for LeY, as well as nick-end labeling for the detection of DNA breaks, was done on cervical spinal cord sections from ten patients with amyotrophic lateral sclerosis (ALS) and nine patients who had died from other causes. LeY-positive immunoreactivity was seen in the motor neurons of seven ALS cases, but in none of the other cases. Nick-end labeling was also positive in four ALS cases. Double staining of motor neurons by anti-LeY antibody and nick-end labeling was shwon in these cases. Other LeY-positive structures, such as reactive astrocytes and fat-laden microglia/macrophages in the lateral and anterior columns, were negative for nick-end labeling. These results suggest that the mechanism of cell death in the spinal motor neurons of ALS may be apoptosis.
    Materialart: Digitale Medien
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  • 2
    ISSN: 1432-0533
    Schlagwort(e): Proliferating cell nuclear antigen (PCNA) ; Ki-67 ; Medulloblastoma ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The distribution of proliferating cell nuclear antigen (PCNA)-(clone PC 10)- and Ki-67- (clone MIB-1)-positive nuclei was investigated in 60 medulloblastomas of childhood. Although the labeling index of the two markers did not coincide, both showed a wide range of parallel variations. The percentage of positive nuclei was similar in both classic and desmoplastic tumors. A variable proliferation capacity was found in the different tumor structures. Areas with neuronal and glial differentiation showed very few positive nuclei; these were very abundant in the infiltration areas, and along penetrating vessels from subarachnoidal growths. Pale islands were negative or positive only in their peripheral part. Large-cell areas were richer in positive nuclei than classic ones, accounting for their more malignant character. Hyperchromatic round nuclei, not belonging to necrotic foci and called lymphocyte-like nuclei, differently interpreted in the past, were vairiably found in every case. They are known, from previous experience, to stain orange with Acridine Orange fluorochroming, like single-stranded DNA. They were not easily distinguishable from mitoses and were stained by in situ end-labeling of DNA strand breaks, as demonstrated by incorporation of labeled nucleotides. They were regarded as possible apoptotic nuclei, representing either a peculiar type of cell death or the preservation of the cell deletion capacity, typical of the embryonal tissue of origin.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1432-0533
    Schlagwort(e): Amyotrophic lateral sclerosis ; LeY Nick-end labeling ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Expression of LeY, a difucosylated type 2 chain determinant, has been previously identified as a characteristic of cells undergoing apoptosis. Immunohistochemistry using an antibody for LeY, as well as nick-end labeling for the detection of DNA breaks, was done on cervical spinal cord sections from ten patients with amyotrophic lateral sclerosis (ALS) and nine patients who had died from other causes. LeY-positive immunoreactivity was seen in the motor neurons of seven ALS cases, but in none of the other cases. Nickend labeling was also positive in four ALS cases. Double staining of motor neurons by anti-LeY antibody and nick-end labeling was shwon in these cases. Other LeY-positive structures, such as reactive astrocytes and fatladen microglia/macrophages in the lateral and anterior columns, were negative for nick-end labeling. These results suggest that the mechanism of cell death in the spinal motor neurons of ALS may be apoptosis.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Anatomy and embryology 189 (1994), S. 435-440 
    ISSN: 1432-0568
    Schlagwort(e): Apoptosis ; Primordial germ cells ; Mouse embryo ; Gametogenesis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A detailed study of the death in vitro of mouse primordial germ cell (PGCs) by means of transmission and scanning electron microscopy is reported. The results show that after 4–5 h of culture 15–20% PGCs assume the typical morphological features of apoptotic cells, including chromatin condensation in dense masses under the nuclear membrane, compaction of the cytoplasm, crowding of organelles and surface protuberances. Cells then break up into discrete fragments (apoptotic bodies) which eventually degenerate by “secondary necrosis”. It is possible that apoptosis plays a biologically useful role in avoiding uncontrolled PGC proliferation and in eliminating misplaced germ cells whose survivial might be harmful to the animal.
    Materialart: Digitale Medien
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  • 5
    ISSN: 1432-0584
    Schlagwort(e): Anthracycline ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary We have studied some of the factors involved in the cytotoxic actions of the anticancer anthracycline antibiotics doxorubicin (DOX) and idarubicin (IDA) towards human B-cell lymphoma cells in vitro. IDA was found to accumulate within cells to a greater degree than the related drug DOX for both short (1 h) and long-term (24 h) exposures. Both agents showed a similar capacity for trapping topoisomerase II in intact cells, but cross-linking activity was significantly lower than that induced by the specific poison VP16. IDA was four- to eight fold more potent for the induction of cytostasis and cell cycle arrest and for the instigation of DNA breakdown as a prelude to the full expression of apoptosis. Inhibition of DNA fragmentation at higher drug doses was linked closely with the inhibition of S-phase traverse. The findings suggest that DOX and IDA act in a similar fashion, the latter agent being more effective due to enhanced intracellular accumulation. We conclude that the presence of drug and topoisomerase II-associated DNA damage is not sufficient to induce DNA fragmentation; rather, unregulated commitment to S-phase traverse is an important factor in the activation of programmed cell death.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1423-0127
    Schlagwort(e): Adenosine ; Adenosine deaminase deficiency ; Apoptosis ; c-myc ; DNA fragmentation ; Proto-oncogene ; L1210 lymphocytic leukemia cells ; Severe combined immunodeficiency syndrome
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract High concentrations of adenosine (Ado), when added to L1210 lymphocytic leukemia cells, resulted in apoptosis or programmed cell death. The apoptotic process was accompanied by distinct morphological changes including chromatin condensation and blebbing of plasma membranes. Extensive DNA fragmentation was correlated with Ado concentrations. Furthermore, apoptosis in these cells was preceded by an early but transient expression of c-myc proto-oncogene, and was not influenced by homocysteine thiolactone added to the cells. Since severe combined immunodeficiency (SCID) is associated with a deficiency of adenosine deaminase, leading to defects in both cellular and humoral immunity, Ado-induced apoptosis may thus be a contributing factor in the pathology of SCID.
    Materialart: Digitale Medien
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  • 7
    ISSN: 1432-0843
    Schlagwort(e): Apoptosis ; DNA fragmentation ; HL-60 cells ; Ara-C ; Mitoxantrone ; Taxol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We investigated the ability of different doses and durations of exposure to the chemotherapeutic drugs 1-β-d-arabinofuranosylcytosine (Ara-C), mitoxantrone (MTN), and paclitaxel (taxol, TXL) to induce internucleosomal DNA fragmentation and apoptosis in human acute myeloid leukemia (AML) HL-60 cells in suspension culture. At clinically achievable concentrations, all three drugs have been shown to induced apoptosis in HL-60 cells. An improved method was developed for the isolation of pure genomic DNA and the detection of drug-induced intergenomic DNA and the detection of drug-induced internucleosomal DNA fragmentation in 〈1.0 μg of DNA sample by agarose gel electrophoresis. Morphologic evidence for apoptosis was determined by light microscopy following Wright staining, and cell viability was assessed by trypan blue dye exclusion. Internucleosomal DNA fragmentation was observed following exposure to 1.0 μM Ara-C for 4 h, which increased with 10 and 50 μM Ara-C. Incubation with 100 μM Ara-C produced internucleosomal DNA fragmentation starting at 3 h, which increased with longer periods of exposure to Ara-C. Utilizing a schedule of 1-h exposure followed by 3-h suspension in drug-free medium, 0.25 μM MTN was found to initiate DNA fragmentation, which increased with exposure to 1.0 and 5.0 μM MTN. However, identical treatment with higher concentrations of MTN resulted in random DNA degradation. Alternatively, continuous exposure to 1.0 μM MTN for 3 h was necessary to initiate internucleosomal DNA fragmentation. This increased with exposure intervals of up to 6 h. Exposure to TXL concentrations as low as 0.01 μM for 24 h caused internucleosomal DNA fragmentation, which increased with dose escalation (0.05, 0.1, 0.5, and 1.0 μM) of TXL. Although continuous exposure to 1.0 μM TXL for a period as short as 8 h produced internucleosomal DNA fragmentation, this increased significantly with longer exposure intervals. In general there appears to be a threshold concentration and duration of exposure below which non of these three drugs activates endonucleolytic internucleosomal DNA fragmentation and apoptosis. This threshold is lower for the DNA-interactive drugs MTN and Ara-C but higher for the non-DNA-interactive drug TXL. Higher doses or prolonged treatments with the drugs produce random DNA fragmentation associated with necrotic cell death. These in vitro results may further improve our understanding of the antileukemic cytotoxic effects of these drugs, which may enable a more rational design of drug regimens for optimal treatment of AML.
    Materialart: Digitale Medien
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  • 8
    ISSN: 1432-0843
    Schlagwort(e): Etoposide ; Topoisomerase II ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A number of clinically important drugs such as the epipodophyllotoxins etoposide (VP-16) and teniposide (VM-26), the anthracyclines daunorubicin and doxorubicin (Adriamycin), and the aminoacridine amsacrine exert their cytotoxic action by stabilizing the cleavable complex formed between DNA and the nuclear enzyme topoisomerase II. We have previously demonstrated in several in vitro assays that the anthracycline aclarubicin (aclacinomycin A) inhibits cleavable-complex formation and thus antagonizes the action of drugs such as VP-16 and daunorubicin. The present study was performed to validate these in vitro data in an in vivo model. At nontoxic doses of 6 and 9 mg/kg, aclarubicin yielded a marked increase in the survival of non-tumor-bearing mice given high doses of VP-16 (80–90 mg/kg) in six separate experiments. In therapy experiments on mice inoculated with Ehrlich ascites tumor cells, aclarubicin given at 6 mg/kg roughly halved the increase in median life span induced by VP-16 at doses ranging from 22 to 33 mg/kg. An attempt to determine a more favorable combination of VP-16 and aclarubicin by increasing VP-16 doses failed, as the two drugs were always less effective than VP-16 alone. The way in which VP-16-induced DNA strand breaks lead to cell death remains unknown. However, VP-16 has been reported to cause apoptosis (programmed cell death) in several cell lines. To ascertain whether the protection given by aclarubicin could have a disruptive effect on the apoptotic process, we used the small intestine as an in vivo model. Whereas VP-16-induced apoptosis in crypt stem cells was detectable at a dose as low as 1.25 mg/kg, aclarubicin given at up to 20 mg/kg did not cause apoptosis. Indeed, aclarubicin caused a statistically significant reduction in the number of cells rendered apoptotic by VP-16. The present study thus confirms the previous in vitro experiments and indicates the value of including an in vivo model in a preclinical evaluation of drug combinations.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1432-1335
    Schlagwort(e): Coumarin ; Benzopyrone ; 7-Hydroxycoumarin ; Amitumor activity ; Growth inhibition ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Coumarin (1,2-benzopyrone) is a natural substance that has shown antitumor activity in vivo. The major human metabolite of coumarin, 7-hydroxycoumarin (7-HC), is the active form of the drug. While the exact mechanism(s) of action of coumarin is unknown, it has been shown previously that this drug possesses immunomodulatory activity in vitro and in vivo. The present investigations examined the direet (non-immunological) antitumor effects of coumarin and 7-HC in vitro. Both coumarin and 7-HC were found to be growth-inhibitory (cytostatic) for the following human malignant cell lines: A549, ACHN, Caki-2, Dakiki, HS-Sultan, H727, HCT-15, HL-60, K562, LNCaP, PC-3, Du 145 COLO-232, MCF-7 and RP-1788. The growth inhibition was dependent on dose and time and was reversible upon removal of cells from medium containing the drug. Coumarin and 7-HC inhibited [3H]thymidine, [3H]uridine and [3H]leucine incorporation. In a similar fashion, coumarin and 7-HC inhibited the intracellular production of prostate-specific antigen by LNCaP cells. Coumarin and 7-HC stimulated apoptosis in HL-60 cells but not in other cell lines tested. It is concluded that coumarin and 7-HC have direct antitumor (cytostatic) activity as well as immunomodulatory activity. Further information is needed in order to determine which activities are responsible for antitumor activity in vivo.
    Materialart: Digitale Medien
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  • 10
    ISSN: 1432-1963
    Schlagwort(e): Schlüsselwörter bcl-2 ; Osteosarkom ; Apoptose ; programmierter Zelltod ; Immunhistologie ; Proliferation ; Key words bcl-2 ; Osteosarcoma ; Apoptosis ; programmed cell death ; Immunohistochemistry ; Proliferation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary The relationsship between the growth of tumors and the expression of the protooncogen Bcl-2 could be shown in epithelial tumors. A bcl-2 expression leads to a prolonged cell survival due to an inhibition of apoptosis. The potential meaning of bcl-2 expression in mesenchymal tumors remains still unknown. The fact, that the heterogenous group of osteosarkoma is not sufficiently characterized at present, suggested to investigate the bcl-2 expression in osteosarcoma. Thus, immunohistochemistry was used to analyze 47 specimens of different osteosarcomas of 36 patients. Sixteen cases (46 %) showed a strong expression of bcl-2 and 13 cases (35 %) were moderately positiv for bcl-2. Seven cases (19 %) were negative for bcl-2. The heterogenous, negative up to strong expression of bcl-2 yield clues, that the Bcl-2 controlled regulation of programmed cell death could be an important factor of cellular kinetics. Additionally the cellular proliferationrate was determined with the monoklonal antibody MIB 1, directed against the Ki-67 epitop. The data of bcl-2 expression and cellular proliferationrate lead to a classification correlating with the histological classification. To verify the importance of apoptosis in the genesis of mesenchymal tumors and whether Bcl-2 may play an important role as a predictive factor for the prognosis of osteosarcoma, further investigations will be needed.
    Notizen: Zusammenfassung Bei zahlreichen epithelialen Geweben konnte ein Zusammenhang zwischen Tumorwachstum und der Expression des Protoonkogens Bcl-2 nachgewiesen werden. Eine bcl-2-Expression ist verbunden mit verlängertem Zellüberleben infolge einer Apoptoseinhibition. Hingegen ist über die bcl-2-Expression und deren mögliche Bedeutung in mesenchymalen Tumoren wenig bekannt. Da die heterogene Gruppe der Osteosarkome mit den derzeitigen methodischen Mitteln nicht hinreichend charakterisierbar ist, wurde die bcl-2-Expression untersucht. Immunhistologisch wurden 47 Osteosarkompräparate von 36 Patienten unterschiedlicher Subtypen analysiert. Von den 36 Fällen zeigten in der Biopsie 16 Fälle (46 %) eine stark positive und 13 Fälle (35 %) eine mittelgradig positive bcl-2 Expression. Sieben Fälle (19 %) waren bcl-2-negativ. Die heterogene, fehlende bis starke bcl-2-Expression deutet darauf hin, daß in Osteosarkomen die Bcl-2-gesteuerte Regulation des programmierten Zelltodes einen Faktor in der zellulären Wachstumskinetik darstellt. Zusätzlich wurde die Proliferationsrate, anhand des gegen das Ki-67-Antigen gerichteten monoklonalen Antikörper MIB-1 bestimmt. Aus den Daten zur bcl-2-Expression und Proliferationsrate ergibt sich eine Einteilung, die eine Übereinstimmung mit der histologischen Klassifikation aufweist. Welche Bedeutung die Apoptose in der Genese mesenchymaler Tumoren hat und ob die bcl-2-Expression einen prädiktiven Wert für die Prognose von Osteosarkomen besitzt, bedarf weiterer Untersuchungen.
    Materialart: Digitale Medien
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  • 11
    Digitale Medien
    Digitale Medien
    Springer
    Pediatric nephrology 8 (1994), S. 377-382 
    ISSN: 1432-198X
    Schlagwort(e): Apoptosis ; immune regulation ; development
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
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  • 12
    Digitale Medien
    Digitale Medien
    Springer
    Bioscience reports 14 (1994), S. 67-81 
    ISSN: 1573-4935
    Schlagwort(e): Apoptosis ; programmed cell death
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Apoptosis is a normal physiological cell death process of eliminating unwanted cells from living organisms during embryonic and adult development. Apoptotic cells are characterised by fragmentation of nuclear DNA and formation of apoptotic bodies. Genetic analysis revealed the involvement of many death and survival genes in apoptosis which are regulated by extracellular factors. There are multiple inducers and inhibitors of apoptosis which interact with target cell specific surface receptors and transduce the signal by second messengers to programme cell death. The regulation of apoptosis is elusive, but defective regulation leads to aetiology of various ailments. Understanding the molecular mechanism of apoptosis including death genes, death signals, surface receptors and signal pathways will provide new insights in developing strategies to regulate the cell survival/death. The current knowledge on the molecular events of apoptotic cell death and their significance in health and disease is reviewed.
    Materialart: Digitale Medien
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  • 13
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 277 (1994), S. 485-491 
    ISSN: 1432-0878
    Schlagwort(e): Key words: Skin ; Club cells ; Apoptosis ; Necrosis ; Filament cells ; Leucocytes ; Cyprinus carpio (Teleostei)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract. The ultrastructure of club cells and neighbouring filament cells and leucocytes in the epidermis of carp, was studied under normal conditions and after exposure to several stressors: acid water, heavy metals, organic manure, brackish water and wounding. The effects of the stressors were remarkably similar. The club cells increased in size and contained more endoplasmic reticulum and Golgi areas. In both control and stressed fish, most mitotic figures of the filament cells were found adjacent to club cells, as was demonstrated after colchicine injection. Whereas in the controls apoptosis of filament cells was scarce and limited to the upper layer of the epithelium, in the stressed fish it was commonly seen in close proximity to the club cells but not in other mid-epidermal parts of the epithelium. This indicates that club cells influence the cellular kinetics of the filament cells. Under stress conditions leucocytes infiltrated the epidermis. Some were seen inside club cells. Apparently these leucocytes were taken up in phagosomes and subsequently they showed signs of necrotic degeneration. Leucocyte incorporation and degeneration in club cells were not observed in control fish. Control of the cellular turnover of filament cells and the elimination of leucocytes may represent new functions for club cells, which have mainly been associated with the production of pheromones.
    Materialart: Digitale Medien
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  • 14
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 277 (1994), S. 485-491 
    ISSN: 1432-0878
    Schlagwort(e): Skin ; Club cells ; Apoptosis ; Necrosis ; Filament cells ; Leucocytes ; Cyprinus carpio (Teleostei)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The ultrastructure of club cells and neighbouring filament cells and leucocytes in the epidermis of carp, was studied under normal conditions and after exposure to several stressors: acid water, heavy metals, organic manure, brackish water and wounding. The effects of the stressors were remarkably similar. The club cells increased in size and contained more endoplasmic reticulum and Golgi areas. In both control and stressed fish, most mitotic figures of the filament cells were found adjacent to club cells, as was demonstrated after colchicine injection. Whereas in the controls apoptosis of filament cells was scarce and limited to the upper layer of the epithelium, in the stressed fish it was commonly seen in close proximity to the club cells but not in other mid-epidermal parts of the epithelium. This indicates that club cells influence the cellular kinetics of the filament cells. Under stress conditions leucocytes infiltrated the epidermis. Some were seen inside club cells. Apparently these leucocytes were taken up in phagosomes and subsequently they showed signs of necrotic degeneration. Leucocyte incorporation and degeneration in club cells were not observed in control fish. Control of the cellular turnover of filament cells and the elimination of leucocytes may represent new functions for club cells, which have mainly been associated with the production of pheromones.
    Materialart: Digitale Medien
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  • 15
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 278 (1994), S. 549-556 
    ISSN: 1432-0878
    Schlagwort(e): Apoptosis ; Necrosis ; Cell death ; DNA fragmentation ; Endogenous nuclease ; Actinomycin D ; Ionomycin ; Confocal laser microscopy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The occurrence and spatial distribution of intracellular DNA fragmentation was investigated by in situ 3′ end labelling of DNA breaks in K562 cells treated in such a way to cause either apoptotic or necrotic cell death. The localisation of DNA breaks was examined by confocal laser microscopy and compared with the electron-microscopic appearance of the cells. In addition, the number of cells with fragmented DNA was counted and compared with the number of dead cells, as determined by the nigrosin dye exclusion test. Apoptosis was induced by cultivation of the cells in the presence of actinomycin D. Cells undergoing apoptosis were characterised by massive intracellular DNA fragmentation that was highly ordered into successive steps. Cells in early stages of the apoptotic process had DNA breaks diffusely distributed in the entire nucleus, except the nucleolus, with crescent-like accumulations beyond the nuclear membrane. In the more advanced stages, the nucleus was transformed into many round bodies with intense labelling. Intracellular accumulations of fragmented DNA corresponded exactly to electron-dense chromatin seen in the electron microscope, whereas diffuse DNA breaks had no morphological correlate at the ultrastructural level. In necrosis induced by ionomycin, NaN3, or rapid freezing combined with thawing, no DNA fragmentation occurred at the onset of cell death, but appeared 24 h later. This fragmentation was not characterised by a unique morphology, but represented the breakdown of the chromatin in the configuration remaining after cell death. Therefore, apoptosis is characterised by DNA fragmentation that proceeds in a regular orderly sequence at the beginning of cell death, and can be detected by in situ 3′end labelling of DNA breaks.
    Materialart: Digitale Medien
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  • 16
    Digitale Medien
    Digitale Medien
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 240 (1994), S. 261-266 
    ISSN: 0003-276X
    Schlagwort(e): Germ cell ; Apoptosis ; Ovary ; TEM ; SEM ; Chick embryo ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Background: Embryonic chick ovary forms medulla and cortex successively in early developmental stages. Unlike the cortex, which is a functioning tissue in the adult, the medulla regresses as development advances. Although germ cells are included in these respective regions, their behavior within these regions is different. This study focuses on the fate of germ cells in the medulla of both ovaries.Methods: Germ cells found in the medulla of the developing chick ovary from 7 to 19 days of incubation were observed by TEM and SEM.Results: From 10 days of incubation onward, medullary germ cells in both right and left ovaries were often released into medullary lacunae. During the releasing process, germ cells were covered by thin cytoplasm of epithelial cells of the lacunae. After release, however, they were freed from the thin coat of epithelial cells. Abandoned germ cells were seen in the lacunae as solitary cells or as a mass composed of several cells. In the right ovary, germ cells released into the lacunae were subsequently found at the holes of the ovarian surface, which were continuous with the medullary lacunae. Moreover, germ cell death was often found in late stages in the medullary tissues of both right and left ovaries.Conclusions: The present study clarifies the fact that chick germ cells of the medulla of both right and left ovaries are either discarded by a process of programmed cell death and/or released into medullary lacunae with increasing embryo age. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 7 Ill.
    Materialart: Digitale Medien
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  • 17
    Digitale Medien
    Digitale Medien
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 240 (1994), S. 115-119 
    ISSN: 0003-276X
    Schlagwort(e): ACPI ; Cystatin A ; Thymus ; Thymocyte ; Apoptosis ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Background: Acid cysteine proteinase inhibitor (ACPI, also called cystatin A) is a protein that is present in the epithelial cells of the skin and in the dendritic reticulum cells of lymphoid tissues. In this study the presence and cellular localization of ACPI in the thymus was investigated.Methods: The cellular and topographical location of ACPI was immunohistochemically demonstrated in the normal thymus of man.Results: ACPI was found in the cells of the-Hassall's corpuscles and in many medullary cells. Most of these cells were epithelial cells, as shown by the results of immunohistochemical cytokeratin and epithelial membrane antigen stainings. Also, some individual cytokeratin negative but S-100 positive medullary reticular dendritic cells were stained with ACPI.Conclusions: The finding that ACPI is constantly present in the thymus at restricted and specific cellular locations leads to the suggestion that protease inhibitors may play a role in specific thymic functions. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 8 Ill.
    Materialart: Digitale Medien
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  • 18
    Digitale Medien
    Digitale Medien
    New York, NY [u.a.] : Wiley-Blackwell
    Developmental Dynamics 199 (1994), S. 176-188 
    ISSN: 1058-8388
    Schlagwort(e): Bcl-2 ; Apoptosis ; Programmed cell death ; Human fetal skin morphogenesis ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: During human skin development, embryonic- and fetal-specific periderm cells and incompletely keratinized cells are replaced by keratinocytes that differentiate while stratifying to form the fully functional epidermis. Proliferating basal cells of fetal skin also develop into epidermal appendages such as hair follicles and glands. We demonstrate that programmed cell death, not emphasized in conventional epidermal biology, has an important function in establishing the final architecture of the human epidermis and its appendages. Immunohistochemical localization of transglutaminases in fetal periderm, intermediate epidermal cells, and within appendages coincides with DNA fragmentation indicating that apoptosis is involved in deletion of these stage-specific cells and remodeling of appendages. The data also suggest that terminal differentiation of epidermal cells might be a specialized form of apoptosis. The pattern of expression of bcl-2, a gene associated with survival of some cells, is exclusive of the distribution patterns of markers of the cell death pathway. Bcl-2 protein is correlated with specific morphogenetic events in hair follicles and eccrine sweat glands, and its presence in single cells of the hair follicle bulge suggests that Bcl-2 may be a stem cell marker. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 7 Ill.
    Materialart: Digitale Medien
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  • 19
    Digitale Medien
    Digitale Medien
    New York, NY [u.a.] : Wiley-Blackwell
    Microscopy Research and Technique 28 (1994), S. 327-344 
    ISSN: 1059-910X
    Schlagwort(e): Apoptosis ; Granulocytes ; Aging ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Allgemeine Naturwissenschaft
    Notizen: The present study provides experimental data which indicate that the neutrophil is ideal for studying programmed cell death or apoptosis in vitro. Neutrophils can be obtained from human peripheral blood in large numbers with minimal experimental manipulation and are easily separated from other leukocytes, providing nearly pure cell suspensions. The neutrophil life span in vitro is sufficiently short to allow observations to be made within eight hours after experimental manipulation. Neutrophils can also be easily maintained in serum-free, chemically defined media which can be systematically altered, thereby defining specific variables that influence the apoptotic process. Since the neutrophils do not need an exogenous trigger to undergo programmed cell death, it is also an excellent model to study senescence. It was determined from this study that neutrophils undergo apoptosis most efficiently at 37°C, a temperature requirement for physiologic cell death. Neutrophils undergo apoptosis at a slightly faster rate and maintain membrane integrity better when incubated in a tissue culture medium (e.g., RPMI 1640) compared with a balanced salt solution (e.g., HBBB). Cycloheximide, an inhibitor of protein synthesis, was shown to accelerate apoptosis in a dose-dependent manner. The presence of Zn++ significantly decreased the rate of apoptosis, whereas the presence of Ca++ and Mg++ had no apparent effect. These studies indicate that the process of senescence, culminating in cell death, is subject to modulation by a variety of agents and experimental conditions. In addition, the ultrastructural features of neutrophils undergoing programmed cell death in vitro were compared in detail to those occurring in vivo and were found to be comparable. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 9 Ill.
    Materialart: Digitale Medien
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  • 20
    Digitale Medien
    Digitale Medien
    Springer
    Cancer immunology immunotherapy 36 (1993), S. 149-155 
    ISSN: 1432-0851
    Schlagwort(e): Apoptosis ; DNA fragmentation ; Cellular cytotoxicity ; NK cells
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Apoptosis in three lymphoma cell lines has been studied following cytotoxicity induced in vitro by normal human blood lymphocytes utilizing either natural killer (NK) or antibody-dependent cellular cytotoxic (ADCC) mechanisms. Guinea-pig L2C leukaemic lymphocytes, but not the human cell lines Daudi and Jurkat, revealed a degree of time- and temperature-dependent apoptotic death upon simple culture in vitro. NK cytotoxicity at low effector: target ratios (E: T) induced both release of51Cr and apoptosis. However NK cytotoxicity at higher E : T, and ADCC at all E : T, increased the level of51Cr release while reducing the level of apoptosis. The findings were consistent with the apoptotic process being cut short by intervention of necrotic death. The same characteristics accompanied ADCC whether the effectors were recruited by Fcγ regions of antibody coating the targets, or by bispecific antibodies attaching one arm to the targets and the other to Fcγ receptors type III on effectors. This finding, and the high level of cytotoxicity elicited by the bispecific method, confirm the belief that NK cells, in addition to exerting NK cytotoxicity, represent the principal effectors for ADCC among blood mononuclear cells. Our results suggest that NK cells have both apoptotic and necrotic mechanisms available for killing their targets, but use only the latter for ADCC.
    Materialart: Digitale Medien
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  • 21
    ISSN: 1433-2981
    Schlagwort(e): Apoptosis ; Blood cells ; Hepatic haemopoiesis ; Hibernation ; Urodeles
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Morphocytochemical correlation between proliferation (BrdU uptake) of the haemopoietic liver subcapsular tissue and peripheral blood cell characteristics was performed during active (summer) and hibernating (winter) periods in two Urodele species: Triturus carnifex and Triturus alpestris. The significant decrease of the haemopoietic cell proliferation during the hibernation was accompanied by some modifications both at erythrocyte and leucocyte level. This situation was primarily characterised by a hypofunctionality and ageing of these cells with the disappearance of immature elements from the circulation and cell loss by apoptotic mechanisms. The results indicate that the condition of low metabolism during the winter period in these Urodeles involved deep changes in the physiology of haemopoietic tissue and blood circulating cells.
    Materialart: Digitale Medien
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  • 22
    ISSN: 1432-2307
    Schlagwort(e): Prostate gland ; Apoptosis ; Benign prostatic hyperplasia ; Prostatic intraepithelial neoplasia ; Invasive adenocarcinoma of the prostate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The aim of our study was to assess the frequency and location of apoptotic bodies (ABs) in haematoxylin and eosin-stained sections of prostatic intra-epithelial neoplasia (PIN) and then to compare the patterns with those in benign prostatic hyperplasia (BPH) and prostatic invasive adenocarcinoma (PAC). ABs were identified in all epithelial cell layers of the ducts, acini and tumour islands, as well as in the lumina contained in such structures. In the epithelial cell layers, ABs were found in general in the intercellular space and occasionally in the cytoplasm of epithelial cells. The frequency of ABs increased from BPH through PIN up to PAC. The proportions of ABs in PIN lesions of low grade (PINlow) and high grade (PINhigh) were greater than in BPH, the values decreasing from the nuclei in the basal position towards those in the luminal layer. In PINlow, the mean category values were 0.85% (standard error, SE, 0.311%) in the basal, 0.623% (SE 0.065%) in the intermediate and 0.474% (SE 0.138%) in the luminal position. In PINhigh, the mean category values were 1.006% (SE 0.16%) in the basal position, 0.713% (SE 0.182%) in the intermediate and 0.618% (SE 0.172%) in the luminal position. The proportions of ABs in adenocarcinoma with cribriform pattern decreased from the basal towards the luminal layer, as for PIN: 1.806% (SE 0.346%) in the basal position, 1.15% (SE 0.172%) in the intermediate and 0.886% (SE 0.137%) in the luminal position. In the solid/trabecular adenocarcinomas, the mean category value in the cell layer adjacent to the stroma was 2.154% (SE 0.203%), whereas in the other cell layers it was 2.052% (SE 0.239%). In small and large acinar adenocarcinomas, the proportions of positive nuclei were 1.022% (SE 0.1%) and 0.922% (SE 0.163%), respectively. The evaluation of the frequency and location of ABs gives accurate information on cell death in PIN in comparison with BPH and PAC.
    Materialart: Digitale Medien
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  • 23
    Digitale Medien
    Digitale Medien
    Springer
    Archives of toxicology 67 (1993), S. 318-324 
    ISSN: 1432-0738
    Schlagwort(e): Chick embryo ; DNase I ; DNase I inhibitors ; DNA fragmentation ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Chicken embryo brain and liver cells in vitro exhibited spontaneous DNA fragmentation as determined by viscometry of alkaline cell lysates. Ca2+ and Mg2+ enhanced, while Zn2+, the Ca2+ chelator ethylenglycolbis(β-aminoethyl-ether)-N, N, N′-tetraacetic acid (EGTA), spermine and — to a lesser extent — spermidine and Hoechst 33258 inhibited spontaneous DNA fragmentation. Under the same conditions chromatin condensation, as assessed by nucleoid sedimentation, increased. Exposure of chicken embryo cells to various genotoxic agents, i.e. doxorubicin, bleomycin, methyl methanesulfonate, thiyl radicals, H2O2, UV light, and X-rays, increased DNA fragmentation in a dose dependent manner. Zn2+ or EGTA diminished DNA fragmentation in cells exposed to bleomycin, thiyl radicals, H2O2 and UV light. An apparent sensitisation to X-irradiation has been observed in Zn2+ or EGTA-pretreated cells. It is suggested by the present investigations that, with agent specific peculiarities, apoptotic phenomena are implicated when nucleotoxicity is assessed in chicken embryo cells by physico-chemical short-term tests in vitro.
    Materialart: Digitale Medien
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  • 24
    Digitale Medien
    Digitale Medien
    Springer
    Archives of toxicology 67 (1993), S. 231-236 
    ISSN: 1432-0738
    Schlagwort(e): Tributyltin ; Thymic atrophy ; Immunotoxicity ; Apoptosis ; In vivo ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Tributyltin (TBT) immunotoxicity in rodent species is primarily characterised by T-lymphocyte deficiency resulting from a depletion of cortical thymocytes. In this study, bis(tri-n-butyltin) oxide (TBTO) was administered to male rats as a single oral dose of 30 or 60 mg/kg, and assessments were made of thymic cytopathology and the integrity of cellular DNA. TBTO treatment did not cause severe toxicity or overt clinical signs; however, by 48 h post-dosing relative thymus weights at 30 and 60 mg/kg were reduced to 66 and 43%, respectively, of control values. Increased DNA fragmentation was evident in thymic cell isolates (principally thymocytes) obtained from treated animals during the period of thymic involution. When DNA purified from these cells was visualised by agarose gel electrophoresis a multimeric internucleosomal fragmentation pattern, indicative of supra-physiological levels of apoptosis, was detected. Although unassociated apoptotic or necrotic thymocytes were essentially absent in cell preparations from TBTO-treated rats, significantly increased numbers of mononuclear phagocytic cells were observed. Many of these cells contained either apoptotic thymocytes, with nuclear morphologies exhibiting chromatin condensation, or cell remnants which were characterised as apoptotic bodies. Dibutyltin, which is a major metabolic dealkylation product of tributyltin, failed to significantly stimulate apoptosis when added to isolated thymocytes in vitro. Collectively, these findings suggest that activation of apoptosis contributes to TBT-induced thymocyte depletion in vivo, and indicate that it is unlikely that the metabolite dibutyltin is responsible for this effect.
    Materialart: Digitale Medien
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  • 25
    ISSN: 1432-0878
    Schlagwort(e): Apoptosis ; Necrosis ; Programmed cell death ; Macrophages ; Ubiquitin ; Botryllus schlosseri (Tunicata)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The blastogenic cycle of the colonial ascidian Botryllus schlosseri concludes in a phase of selective cell and zooid death called takeover. Every week, all asexually derived parental zooids synchronously regress over a 30-h period and are replaced by a new generation. Here we document the sequential ultrastructural changes which accompany cell death during zooid degeneration. The principal mode of visceral cell death during takeover occurred by apoptosis, the majority of cells condensing and fragmenting into multiple membrane-bounded apoptotic bodies. Cytoplasmic organelles (mitochondria, basal bodies, striated rootlets) within apoptotic bodies retained ultrastructural integrity. Dying cells and fragments were then swiftly ingested by specialized blood macrophages or intraepithelial phagocytes and subsequently underwent secondary necrotic lysis. Certain organs (stomach, intestine) displayed a combination of necrotic and apoptotic changes. Lastly, the stomach, which demonstrated some of the earliest regressive changes, exhibited intense cytoplasmic immunostaining with a monoclonal antibody to ubiquitin at the onset of takeover. Affinity-purified rabbit antiserum against sodium dodecyl sulfate-denatured ubiquitin detected a characteristic 8.6-kDa mono-ubiquitin band by Western blot analysis. Collectively, these findings raise the possibility that cell death during takeover is a dynamic process which requires active participation of cells in their own destruction.
    Materialart: Digitale Medien
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  • 26
    Digitale Medien
    Digitale Medien
    New York, NY [u.a.] : Wiley-Blackwell
    Developmental Dynamics 198 (1993), S. 225-239 
    ISSN: 1058-8388
    Schlagwort(e): Chick embryo ; Development ; TNFα ; Cell death ; Apoptosis ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: We have investigated the expression of tumor necrosis factor-α (TNFα)-cross-reactive proteins during the early development of the chick embryo from day 1 to day 6 (H-H stages 5-29) using a polyclonal antibody and two monoclonal antibodies to recombinant mouse TNFα. We have confirmed the cross-reactivity of the antibodies with chicken tissue in Western blotting studies. Proteins of 50 kDa and 70 kDa, showing anti-TNFα cross-reactivity, have been identified during early chick development. In addition, both monoclonal antibodies recognize a 120 kDa protein. These molecules probably represent cytosolic or transmembrane TNF-α-like proteins, similar to those previously identified on the surface of cytotoxic T-lymphocytes. We show by ultrastructural cytochemistry that immunoreactivity can be detected at the surfaces of some cells, suggesting that at least some of the antigen is membrane-associated. The proteins are shown to have a widespread tissue distribution during this period of development. Immunoreactivity is first detected in the gastrulating embryo, in the mesoderm and the endoderm. By day 2, expression is confined to the ectoderm and the endoderm, while at day 3 expression appears in the myotome, the notochord, and in nervous tissue. At day 4 the distribution of reactivity is more extensive and includes the notochord, the sclerotome, and the myotome, while the cranial and spinal nerves also become intensely immunoreactive. Also at this stage, neural tube reactivity becomes localized to the marginal neuroepithelial zone, and the lens fibers become positive. This distribution of staining then persists until 6 days of development. We hypothesize that the expression of TNFα-cross-reactive proteins in early development could be indicative of a role for them in programmed cell death (apoptosis) during differentiation of the notochord, the lens, and the nervous system, and in tissue remodeling. © 1993 Wiley-Liss, Inc.
    Zusätzliches Material: 10 Ill.
    Materialart: Digitale Medien
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  • 27
    Digitale Medien
    Digitale Medien
    New York, NY [u.a.] : Wiley-Blackwell
    Microscopy Research and Technique 25 (1993), S. 223-245 
    ISSN: 1059-910X
    Schlagwort(e): Apoptosis ; Necrosis ; Epithelium ; Decidua ; Uterus ; Rodent ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Allgemeine Naturwissenschaft
    Notizen: During blastocyst implantation and placentation in common laboratory rodents, trophoblast cells come into increasingly more intimate associations with the endometrium and, eventually, are in contact with maternal blood. Uterine cell death is one mechanism for removing uterine tissues, primarily epithelial cells, and decidual cells that intervene between trophoblast cells and maternal blood. Mechanisms of cell death and the signals that initiate and regulate it are not well understood. According to current theories, cell death is either gene-directed or the result of traumatic injury, and classification of cell death is based on ultrastructural and biochemical criteria that hypothetically reflect underlying molecular mechanisms. Although the term apoptosis is extensively used to describe all aspects of gene-directed cell death and the term necrosis to describe traumatic death, ultrastructural studies indicate that there are morphological variations of the established criteria, and these could reflect variations of underlying mechanisms. Recent light and electron microscopic work has shown that timing and ultrastructure of uterine cell death at the gestation site varies with region suggesting that initiation and control of cell death is complicated and that more than one mechanism of cell death may be operative. Current information indicates that uterine cell death is most likely part of an intrinsic response of the endometrium to the conceptus, and other than acting as a stimulus to elicit the uterine response, the conceptus probably plays only a minor role in regulating the death of endometrial cells in these species. © 1993 Wiley-Liss, Inc.
    Zusätzliches Material: 16 Ill.
    Materialart: Digitale Medien
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  • 28
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    Developmental Genetics 14 (1993), S. 148-158 
    ISSN: 0192-253X
    Schlagwort(e): Apoptosis ; DNA fragmentation ; T-cell development ; heat shock proteins ; Life and Medical Sciences ; Genetics
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Notizen: Heat shock protein synthesis was examined in mouse thymocytes at three stages of development: early embryonic thymocytes, which are CD4-CD8-, adult thymocytes, which are primarily CD4+CD8+, and mature spleen T cells, which are CD4+CD8- or CD4-CD8+. After either a 41°C or 42°C heat shock, the synthesis of the maior heat-inducible protein (hsp68) was elevated during the first hour of recovery but then decreased abruptly in thymocytes from adult mice. In contrast, the synthesis of hsp68 continued for up to 4 h after heating embryonic mouse thymocytes or mature spleen T cells. The more rapid termination ofthe heat shock response in the adult thymocytes was not the result of eitherless heat damage or more rapid repair since the recovery of general protein synthesis was more severely delayed in these cells. As well, the double positive CD4+CD8+ cells were more sensitive to hyperthermia than either the double negative CD4-CD8- or single positive CD4+CD8- or CD4-CD8+ cells. Exposure of fetal thymus organ cultures to elevated temperature revealed that the double negative thymocytes were able to survive and differentiate normally following a heat shock treatment that was lethal for the double positive thymocytes. Exposure of thymocytes from adult mice to elevated temperatures induced apoptotic cell death. This was evident by the cleavage of DNA into oligonucleosome-sized fragments. Quantitation of the extent of DNA fragmentation and the number of apoptotic cells by flow cytometry demonstrated that the extent of apoptotic cell death was related to the severity of the heat stress. Double positive (CD4+CD8+) thymocytes are selected on the basis of their T-cell antigen receptor (TCR). Most of these cells are negatively selected and die within the thymus by an active process of cell deletion known as apoptosis. Restricting hsp synthesis in response to stress might be essential during developmental processes in which cell maturation is likely to result in death rather than functional differentiation. © 1993Wiley-Liss, Inc.
    Zusätzliches Material: 4 Ill.
    Materialart: Digitale Medien
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  • 29
    ISSN: 1432-1335
    Schlagwort(e): LH-RH antagonist ; Hormone-suppression ; DMBA mammary carcinoma ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Cetrorelix, (Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10)-LHRH (SB-75) is a new highly potent antagonist of LH-RH. In the model of DMBA-induced mammary carcinoma, this antagonist was very effective in reducing tumor mass. A rapid decrease in tumor weights to levels below 0.1 g total tumor mass was achieved with 300 μg/kg given sc. daily for 14 days. The weights of uteri and ovaries were reduced to about 40–50% of control values. In all treated rats the estrus cycle was interrupted and the animals remained in a state of anestrus. Microscopically, the effects of Cetrorelix on the tumors were characterized by a loss of mitotic activity, marked regression with apoptosis, an increase of stroma and differentiation towards a normal mammary architecture. On the basis of a dose-response curve, a dose of 100 μg/kg/d of Cetrorelix was determined as sufficient for a full antitumor response. Large DMBA-tumors with total tumor mass of about 6 g could also be treated very effectively with a dose of 100 μg/kg/d. To achieve a complete tumor regression, the treatment had to last 34 days. After the cessation of treatment with 100 μg/kg/d and regrowth of the tumors the animals were treated with the agonist Decapeptyl (Trp6-LHRH) using a dose of 50 μg/rat/d for 14 days. Again, the tumors responded well and regressed within 10 days. The treatment with an overlapping dose schedule of Cetrorelix and Decapeptyl showed a continuous antitumor response. A transient stimulation of tumor growth by the LH-RH agonist was not observed under these experimental conditions. In ovariectomized rats bearing DMBA-tumors, treatment with Cetrorelix and estradiol, produced no tumor growth inhibition as compared to estradiol control group, indicating that there is no estrogen nullifying effect of this antagonist on tumor cells in this model. On the basis of these results, Cetrorelix is a highly effective antitumor agent in this breast cancer model, which might also be useful under clinical conditions.
    Materialart: Digitale Medien
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  • 30
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 267 (1992), S. 583-590 
    ISSN: 1432-0878
    Schlagwort(e): Degeneration ; Apoptosis ; Germ cells ; Prespermatogonia ; Testis ; Golden hamster, Mesocricetus auratus (Rodentia)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Degenerating prespermatogonial germ cells in the testis of the immature golden hamster [aged 14 days post conceptionem (dpc) to 13 days post partum [dpp)] were studied with regard to their morphology and temporal incidence. Judged by their ultrastructural features, these cells clearly take the form of apoptosis and finally are subjected to phagocytosis by neighboring Sertoli cells; only a few germ cells of a presumably incipient, partly variant degenerative morphology cannot, at present, be assigned to the apoptotic mode of cellular death. Degenerating prespermatogonia occur between the 14th dpc and 3rd dpp and again, after an interval in which no such cells are found, from the 9th dpp onwards. This pattern reveals a striking parallelism to the phases of proliferation of these cells, viz., the appearance of M- and T2-prespermatogonia. Both this obvious temporal association of proliferation and degeneration and the classification of prespermatogonial death as apoptosis suggest some developmental significance of the degenerative phenomena investigated.
    Materialart: Digitale Medien
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  • 31
    Digitale Medien
    Digitale Medien
    Springer
    Cancer and metastasis reviews 11 (1992), S. 157-178 
    ISSN: 1573-7233
    Schlagwort(e): Apoptosis ; cell death ; growth factors ; tolerance ; affinity maturation ; bcl-2
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The mammalian immune system is essential for surviving challenge infections with a great range of potential pathogens. The protective effect produced is dependent on many different types of cells which require flexible and independent production and regulation. In particular, many important responses are carried out by lymphocytes, which recognise foreign antigen through exquisitely specific receptors: i.e. surface immunoglobulin (sIg) on B lymphocytes and the T cell receptor (TCR) on T lymphocytes. Each lymphocyte displays receptors with a single specificity, allowing cells with particular specificities to be regulated independently. Since millions of different Igs and TCRs are expressed, the precise selection and regulation of each T and B cell population to produce a useful self-tolerant repertoire is a very complex process. Control of cell populations can, in theory, be exercised at a number of levels, including modulation of active cell death by apoptosis. Recent research has demonstrated that regulation of apoptosis is indeed a crucial element in the control of the immune system in general, and in the development of the TCR and Ig repertoires in particular. The molecular analysis of apoptosis now takes a high priority and the protooncogene bcl-2 appears to be responsible for specific suppression of apoptosis in several important situations. It is also clear that malfunctions affecting apoptosis, and in particular bcl-2, can result in significant progression towards malignancy.
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  • 32
    Digitale Medien
    Digitale Medien
    Springer
    Archives of toxicology 65 (1991), S. 135-139 
    ISSN: 1432-0738
    Schlagwort(e): Bis(tri-n-butyl)tin oxide ; Cytotoxicity ; Thymocytes ; Programmed cell death ; Apoptosis ; DNA fragmentation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In order to characterise the mechanism of cytotoxicity of the immunotoxic organotin compound bis(tri-n-butyltin)oxide (TBTO) to lymphoid cells, isolated thymocytes from immature rats were exposed to TBTO (0.1–5 μM) for up to 6 h. At lower TBTO concentrations (0.1 and 1 μM) vital staining showed that only marginal loss of viability occured, although morphological studies demonstrated increased numbers of cells with abnormal features indicative of programmed cell death (apoptosis). These changes included nuclear chromatin condensation (which was associated with increased DNA fragmentation), cytoplasmic contraction and formation of membrane bound apoptotic bodies. When visualised by agarose gel electrophoresis, genomic DNA appeared as a series of fragments with a repeat multiple of 180–200 base pairs. Comparable morphological changes and cleavage of DNA into oligonucleosomal fragments were evident in thymocytes incubated with 10 μM methyl prednisolone hemisuccinate (MPS); a glucocorticoid hormone known to induce programmed cell death in thymocytes. Marked cytotoxicity associated with degenerative changes indicative of necrosis was observed in thymocytes incubated with 5 μM TBTO. These findings indicate that, at levels which are not overtly cytotoxic, TBTO is capable of inducing programmed cell death in rat thymocytes. This suggest a possible mechanism for the T-cell immunodeficiency previously reported for TBTO in vivo.
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  • 33
    Digitale Medien
    Digitale Medien
    Springer
    Archives of toxicology 65 (1991), S. 437-444 
    ISSN: 1432-0738
    Schlagwort(e): Cell death ; Apoptosis ; Necrosis ; Calcium ; Cytoskeleton
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Two distinct morphological patterns of cell death have been recognized, termed necrosis and apoptosis. Apoptosis, or programmed cell death, occurs in both physiological and pathological conditions. It arises due to an elevation of cytosolic free calcium concentration resulting in activation of a nuclear endonuclease. Activated endonuclease produces oligonucleosome-length DNA fragments. This DNA cleavage can directly precipitate cell death. Both glucocorticoids and TCDD may induce apoptosis by production of a heat labile factor that mediates calcium influx whereas tributyltin causes the opening of calcium channels. Evidence that perturbation in calcium homeostasis is an important event in cell necrosis is becoming increasingly persuasive, but the events that propagate the lesion are still unclear. Despite evidence for cytoskeletal disruption, activation of degradative enzymes such as proteases and phospholipase A2 and stimulation of other enzymes such as poly (ADP-ribose) polymerase, the exact role that these play in cell killing is not resolved. Indeed, recently the radical dichotomy between apoptosis and necrotic cell death has come into question. It is clear that further work is required to determine the role played by some elements of the apoptotic process in chemically induced cell death.
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  • 34
    ISSN: 1432-0878
    Schlagwort(e): Apoptosis ; Epidermal growth factor (EGF) ; Neonatal hepatocytes ; Cell proliferation ; Cell culture
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary We recently reported that activation of “tissue” transglutaminase (EC 2.3.2.13; tTG) in liver cells undergoing apoptosis determines extensive cross-linking of cellular proteins resulting in the formation of SDS-insoluble shells in the so-called “apoptotic bodies”. In attempt to obtain further insight into the role played by tTG in apoptosis of liver cells, we investigated its expression in primary cultures of neonatal rat liver cells stimulated with epidermal growth factor (EGF). EGF-treatment of neonatal rat liver cells induces first hyperplasia of hepatocytes, followed by involution characterized by a high incidence of apoptosis. The proliferative phase of hepatocytes is paralleled by a 10-fold increase in tTG mRNA level, which is followed, during the phase of involution, by sequential increases in enzyme activity and levels of SDS-insoluble apoptotic bodies. tTG immunostaining at both the light- and electron-microscopic levels shows that the most intensive reaction is present in globular structures showing the typical morphological appearance of mature apoptotic bodies. In early apoptotic stages, tTG protein is localized in the perinuclear region of the cell. Intense immunostaining is also found in the apoptotic bodies present inside phagosomes within the cytoplasm of neighboring cells. This evidence confirms and extends our previous findings, indicating that tTG induction and activation specifically takes place in cells undergoing apoptosis, suggesting a key role for the enzyme in the apoptotic program.
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  • 35
    ISSN: 0741-0581
    Schlagwort(e): Apoptosis ; Surfactant apoprotein-A ; Blood-nerve barrier ; Pinocytosis ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Allgemeine Naturwissenschaft
    Notizen: Confocal scanning laser microscopy (CSLM) represents an exciting new tool for scientific disciplines which focus on mechanistic studies such as experimental pathology. Enhanced resolution in the specimen plane and rejection of out-of-focus fluorescence flare allow analysis of specific nucleic acid sequences, enzymes, structural macromolecules, and cellular homeostasis utilizing fluorescent probes. Four different experimental applications are discussed which utilize CSLM to evaluate pathological processes at the subcellular, cellular, and tissue levels. Programmed cell death, or apoptosis, is a natural process of significance both during development and as a response to toxic stimuli. CSLM-imaging of nuclei of human B lymphoblastoid cells following exposure to a monofunctional alkylating agent suggests that the degradation of chromatin characteristic of apoptosis may occur in asymmetric patterns. Surfactant apoprotein-A is the major non-serum protein component of pulmonary surfactant and is essential for the extracellular function of surfactant. CSLM of alveolar type II cells suggests that apoprotein-A is present in both the cytoplasm, predominantly in lamellar bodies, and in the nucleus. The tumor promoter, phorbol myristate acetate, rapidly stimulated the formation of vacuoles in human neutrophils. CSLM using Lucifer Yellow as a probe suggests that cylindrical vacuoles are formed by fluid-phase pinocytosis. The blood-nerve barrier (BNB) in peripheral nerves may be an important target during toxin-induced neuropathies. Ricin-induced permeability of the BNB in the rat was rapidly visualized by CSLM as leakage of fluorescein isothiocynate (FITC)-dextran into the endoneurial compartment.
    Zusätzliches Material: 12 Ill.
    Materialart: Digitale Medien
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  • 36
    Digitale Medien
    Digitale Medien
    Springer
    Anatomy and embryology 182 (1990), S. 41-52 
    ISSN: 1432-0568
    Schlagwort(e): Lamprey ; Pronephros ; Ultrastructure ; Regression ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The regression of the pronephric kidney of the lamprey, Petromyzon marinus, is described using histochemical and ultrastructural techniques. Regression begins in the third year of larval life, and by the time the animal enters metamorphosis the tubules have all disappeared. The nephrostomes and the renal corpuscle, however, persist for the remainder of the life cycle and undergo little change in the larva. Iron is present within the tubular epithelium prior to the beginning of degeneration, but as degeneration proceeds iron is observed within the tubule lumina. Acid phosphatase is noted within the tubule epithelia prior to degeneration, but as degeneration proceeds acid phosphatase is also observed within the intertubular area. Features of tubular regression include a prominent and highly folded basal lamina, numerous cytoplasmic inclusions, and dense bodies in the epithelia and lumina. The intertubular region is invaded by lymphocytes, granulocytes, plasma cells, and macrophages. The process of pronephric regression possesses many features of the process of apoptosis, which has been noted in the regression of larval organs in other vertebrates.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 37
    ISSN: 1432-0738
    Schlagwort(e): Cyclophosphamide ; Nuclear aberration assay ; Hair follicles ; Human genotoxicity ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The toxic effect of cyclophosphamide on the proliferative cell population of hair follicles plucked from the human scalp was examined by the in vivo nuclear aberration assay. Patients participating in an independent clinical trial received oral low dose cyclophosphamide, intravenous high dose cyclophosphamide or oral placebo treatment. The percent of cells with nuclear aberrations (indicating apoptosis, a special form of cell death) and the percent of mitotic cells, in the hair matrix, were calculated for each patient before treatment and at several time points following cyclophosphamide or placebo treatment. The mean percentages of nuclear aberrations in both the treated Low dose and High dose cyclophosphamide patients were significantly higher than those for the pre-treatment and Placebo patients. The nuclear aberrations in hair follicle cells increased from pre-treatment (and Placebo) to treated Low dose and finally to treated High dose patients. The average percentage for pre-treatment samples from all patients was 0.06 ±0.03 SE. For 1 week and 1 month samples from Low dose patients it was 0.35 ±0.08 SE, and for combined 2,3 and 4 day samples from High dose patients it was 1.08 ±0.12 SE. Cyclophosphamide also had a significant effect on mitosis. A decrease in mitotic activity was observed at 1 month following the initial low dose cyclophosphamide treatment and at 24±2 h following each of the first two high dose cyclophosphamide treatments. The observed increase in nuclear aberrations following low dose as well as high dose cyclophosphamide suggests that it is feasible to use the nuclear aberration assay for in vivo human genotoxicity testing, using proliferating hair follicle cells.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 38
    ISSN: 1432-0878
    Schlagwort(e): Chloride cells ; Apoptosis ; Gills ; Water acidification ; Oreochromis mossambicus (Teleostei)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Branchial chloride cells, which actively take up ions in the gills of freshwater fish, were studied in tilapia (Oreochromis mossambicus) exposed to sublethally acidified freshwater. Structural damage of cells, resulting in cell death by necrosis, only occurred transiently, when the reduction of water pH was acute rather than gradual. The most prominent effects of water acidification were the rapid increase in the number of chloride cells and the changes in frequency of the different stages of the chloride cell cycle. In the opercular inner epithelium, a twofold increase in cells occurred 48 h after gradual acidification. Cell density stabilized after 4 weeks at a level 5 times that of control fish. Four transitory stages were distinguished in the chloride cell cycle: accessory or replacement cells, immature, mature, and degenerating (apoptotic) cells. In control fish, mature chloride cells dominated (over 50%) with immature and apoptotic cells totalling about 40%. After 4 weeks in acid water, only 13% of the cells were mature. Immature and apoptotic cells dominated, each representing about 40% of the total number of chloride cells. Mature cells apparently age rapidly under these conditions. Thus, chloride cells turn over quickly in acid water, with a minor increase in ion transport capacity of the gills. This conclusion is supported by the observation that opercular and branchial Na+/K+ ATPase activities in treated fish are only 40%–50% higher than in controls.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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