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  • Electronic Resource  (11,146)
  • 2000-2004
  • 1995-1999  (11,146)
  • 1880-1889
  • 1996  (11,146)
  • Chemistry  (11,016)
  • Apoptosis
  • evolution
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Entomologia experimentalis et applicata 80 (1996), S. 163-165 
    ISSN: 1570-7458
    Keywords: olfaction ; EAG ; sensory physiology ; antennal sensitivity ; interspecies hybrids ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Entomologia experimentalis et applicata 80 (1996), S. 7-13 
    ISSN: 1570-7458
    Keywords: host-plant selection ; sensory physiology ; neural coding ; deterrents ; peripheral interactions ; receptor sites ; genetics of insects ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Recent advances in our understanding of the relationship between chemosensory and behavioural responses to phytochemicals come from a number of studies on ovipositional and food selection behaviour of flies, butterflies, moths and beetles. Establishing input-output relationships has provided insight into the way in which the activity of chemoreceptors is translated into host-plant selection behaviour. This was achieved for both the qualitative contrast acceptance/rejection and for quantifiable preference hierarchies. By now it is clear that the subtlety of coding the complex phytochemical profiles offered by potential host plants relies on across-fibre patterns or ensemblefiring of taste neurons. Progress along these lines depends on unravelling processing pathways in the central nervous system, still a largely unexplored area in herbivorous insects. Increased interest can be noted for the mechanisms operating during the most peripheral events of chemoreception: the interaction of phytochemical and chemoreceptor, determining the specificity of recognition. Evidence for ‘peripheral integration’ has accumulated. Deterrent receptors have an especially puzzling nature. Although such cells respond to a wide array of structurally diverse secondary plant metabolites, their sensitivity profile differs between closely related species. To what extent membrane-bound receptor molecules are involved and what degree of specificity is conferred by these, is largely unknown. Sensitivity to a certain group or class of compounds is determined by single genes in several cases. This allows for a scenario in which single gene mutations affect stimulus-receptor interactions, which might concurrently affect host-plant selection behaviour.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Entomologia experimentalis et applicata 80 (1996), S. 320-324 
    ISSN: 1570-7458
    Keywords: multitrophic interactions ; phylogeny ; evolution ; fitness
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 52 (1996), S. 942-949 
    ISSN: 1420-9071
    Keywords: Apoptosis ; transglutaminase ; signalling ; gene expression ; promoter elements ; retinoic acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Clarification of the molecular details of forms of natural cell death, including apoptosis, has become one of the most challenging issues of contemporary biomedical sciences. One of the effector elements of various cell death pathways is the covalent cross-linking of cellular proteins by transglutaminases. This review will discuss the accumulating data related to the induction and regulation of these enzymes, particularly of tissue type transglutaminase, in the molecular program of cell death. A wide range of signalling pathways can lead to the parallel induction of apoptosis and transglutaminase, providing a handle for better understanding the exact molecular interactions responsible for the mechanism of regulated cell death.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 52 (1996), S. 950-956 
    ISSN: 1420-9071
    Keywords: Apoptosis ; integrins ; lectins ; macrophage ; phagocytosis ; scavenger receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Effective removal of dying cells is crucial to a variety of processes in health and disease. Cells undergoing apoptosis are recognized and ingested intact by phagocytes, which are not stimulated to release inflammatory mediators. The alternative uncontrolled form of cell death, necrosis, is associated with release of cell contents with the potential to cause tissue damage and inflammation. Four distinct molecular mechanisms have been identified to date which mediate recognition by phagocytes of mammalian cells undergoing apoptosis, but further mechanisms remain to be discovered. The capacity for phagocyte removal of cells undergoing apoptosis may be closely regulated, for example by local cytokines.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 52 (1996), S. 979-994 
    ISSN: 1420-9071
    Keywords: Apoptosis ; protein tyrosine kinase ; protein kinase C ; cell cycle ; PI3-kinase ; DNA-PK
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The transmission of signals from the plasma membrane to the nucleus involves a number of different pathways all of which have in common protein modification. The modification is primarily in the form of phosphorylation which leads to the activation of a series of protein kinases. It is now evident that these pathways are common to stimuli that lead to mitogenic and apoptotic responses. Even the same stimuli under different physiological conditions can cause either cell proliferation or apoptosis. Activation of specific protein kinases can in some circumstances protect against cell death, while in others it protects the cell against apoptosis. Some of the pathways involved lead to activation of transcription factors and the subsequent induction of genes involved in the process of cell death or proliferation. In other cases, such as for the tumour suppressor gene product p53, activation may be initiated both at the level of gene expression or through pre-existing proteins. Yet in others, while the initial steps in the pathway are ill-defined, it is clear that downstream activation of a series of cysteine proteases is instrumental in pushing the cell towards apoptosis. In this report we review the involvement of protein kinases at several different levels in the control of cell behavior.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 52 (1996), S. 14-24 
    ISSN: 1420-9071
    Keywords: Lycaenidae ; Formicidae ; symbiosis ; mutualism ; parasitism ; communication ; ecology ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Associations with ants, termed myrmecophily, are widespread in the butterfly family Lycaenidae and range from mere co-existence to more or less specific mutualistic or even parasitic interactions. Secretions of specialized epidermal glands are crucial for mediating the interactions. Transfer of nutrients (carbohydrates, amino acids) from butterfly larvae to ants plays a major role, but manipulative communication with the help of odour signals is also involved. By means of myrmecophily, lycaenid butterflies largely escape ant predation, and certain species gain protection through attendant ants or achieve developmental benefits from ant-attendance. Benefits to the ants range from minimal to substantial food rewards. While most lycaenid species maintain facultative relationships with a variety of ant genera, highly specific and obligatory associations have convergently evolved in a number of butterfly lineages. As a corollary, communication systems are largely unspecific in the former, but may be highly specialized in the latter. The sophisticated communication between obligate myrmecophiles and their host ants is tightly connected with the evolutionary rise of specialized life-cycles and thus is a source of augmenting diversity within the butterflies.
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  • 8
    ISSN: 1420-9071
    Keywords: Apoptosis ; Ca2+/Mg2+-dependent endonuclease ; cumulus cell ; granulosa cell ; pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The porcine antral follicles, 3–6 mm in diameter, were dissected from the ovaries of mature pigs, and then granulosa and cumulus cells were isolated from each follicle. In atretic follicles, high activity of neutral Ca2+/Mg2+-dependent endonuclease and DNA ladder formation, estimated by electrophoresis, were noted in granulosa cells but not in cumulus cells. Extremely low activity of the endonuclease and no DNA ladder formation were observed in both types of cells obtained from healthy follicles. Moreover, apoptotic cells were observed histochemically among granulosa cells only. A good correlation (r=0.987) between the endonuclease activity of granulosa cells and the progesterone/estradiol ratio of follicular fluid in each follicle was found. These results suggest that apoptosis occurs in granulosa cells but not cumulus cells in the atretic antral follicles in pigs.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 52 (1996), S. 968-978 
    ISSN: 1420-9071
    Keywords: Apoptosis ; proteases ; ICE-like proteases ; protein substrates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The interleukin-1 β-converting enzyme (ICE)-like family proteases have recently been identified as key enzymes in apoptotic cell death. Among these proteases one can identify specific activities which may be involved in cytokine production or in resident protein cleavage. Several factors influence the constitutive apoptotic mechanism and may provide insight into the role of protease(s) in apoptosis. Although it appears that ICE family members play a most important role in promoting apoptotic cell death, evidence has been advanced that other proteases are also involved in sequential or parallel steps of apoptosis. Activation of a particular protease can lead to processing molecules either of the same or different proteases, leading to an activation of a protease cascade. Here we attempt to summarize the current thinking concerning these proteases and their involvement in apoptosis.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 52 (1996), S. 503-510 
    ISSN: 1420-9071
    Keywords: Drosophila ; accessory gland ; reproduction ; sexual behavior ; sperm displacement ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Recent results from biochemical and molecular genetic studies of the accessory gland proteins in maleDrosophila are reviewed. The most prominent feature is the species-specific variability. However, the analysis of the sex peptide inD. melanogaster shows that there is a strong homology in the molecular structure to the closely related sibling species, and that divergence increases with increasing phylogenetic distance. For this reason the sex peptide, after being transferred to the female genital tract during copulation, reduces receptivity and increases oviposition only in virgin females belonging to the same species group and subgroup. Even though studies were hitherto limited to a small number of the secretory components, it is evident that the accessory gland proteins play a key role in reproductive success of the fruit fly by changing female sexual behavior, supporting sperm transfer, storage and displacement. Thus, genes encoding the accessory gland proteins are apparently under strong evolutionary selection.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 52 (1996), S. 933-941 
    ISSN: 1420-9071
    Keywords: Apoptosis ; necrosis ; macromolecular degradation ; oncogenes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The process of programmed cell death, or apoptosis, has become one of the most intensively studied topics in biological sciences in the last two decades. Apoptosis as a common and universal mechanism of cell death, distinguishable from necrosis, is now a widely accepted concept after the landmark paper by Kerr, Wyllie and Currie in the early seventies [1]. Different components of the death machinery in eukaryotes are discussed in this issue.
    Type of Medium: Electronic Resource
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 52 (1996), S. 957-962 
    ISSN: 1420-9071
    Keywords: Apoptosis ; cyclophilin ; DNA degradation ; NUC18 ; endonuclease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Recent research has focused on identifying the biochemical events associated with the apoptotic process. These include specific degradation of the chromatin which was described by Wyllie in 1980 [1], with the report of the appearance of discretely sized DNA fragments from apoptotic rat thymocytes. The fragments corresponded in size to strands of DNA that were cleaved at internucleosomal regions and create a ‘ladder patterns’ when electrophoresed on an agarose gel. Because of its near universality, internucleosomal DNA degradation is considered a diagnostic hallmark of cells undergoing apoptosis. It is of great interest to identify the enzymes involved, and some of the candidates will be discussed.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 52 (1996), S. 995-1000 
    ISSN: 1420-9071
    Keywords: Apoptosis ; dNTP metabolism ; thymidine kinase ; interleukin-3 ; blc-2 ; hemopoietic cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Fidelity in DNA synthesis and repair is largely dependent on a balanced supply of deoxynucleotide triphosphate (dNTP) pools. Results from different groups have shown that alterations in dNTP supply result in DNA fragmentation and cell death with characteristics of apoptosis. We have recently shown that in apoptosis driven by deprivation of interleukin-3 (IL-3) in a murine hemopoietic cell line, there is a rapid imbalance in the availability of dNTP that precedes DNA fragmentation. In these cells, dNTP pool balance is closely coupled to the function of the salvage pathway of dNTP synthesis. Apoptosis, induced by treatment of these cells with drugs that inhibit the de novo dNTP synthesis, is prevented when dNTP precursors are supplied through the salvage pathway. IL-3 regulates thymidine kinase activity, suggesting that alterations in dNTP metabolism after IL-3 deprivation could be a relevant event in the commitment of hemopoietic cells to apoptosis.
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  • 14
    ISSN: 1437-160X
    Keywords: SLE ; Apoptosis ; bcl-2 gene ; Susceptibility ; Linkage ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by the production of a large number of autoantibodies. It has been postulated that this may be the result of prolonged longevity of auto-reactive B cells due to defective regulation of programmed cell death (apoptosis). The proto-oncogenebcl-2 is involved in the control of apoptosis in immunocompetent cells, and its over-expression is noted in T and B cells from SLE patients. This study examined the genetic linkage between thebcl-2 gene locus and SLE susceptibility using the affected sib-pair method in SLE families. Seventeen caucasian multiplex families were evaluated. A polymorphic microsatellite marker closely linked to thebcl-2 gene on 18g21.3 was used to determine thebcl-2 genotype. We demonstrated that haplotype sharing among the affected sibling pairs was not statistically different from random (P〉0.5). This suggests that thebcl-2 gene locus does not confer a genetic susceptibility to SLE expression.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    International journal of legal medicine 109 (1996), S. 23-28 
    ISSN: 1437-1596
    Keywords: Apoptosis ; Methamphetamine ; Lymphocytes ; Thymus ; Spleen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Notes: Abstract We examined whether methamphetamine (MAP) induced apoptotic cell death in vivo. Male Wistar rats were injected intraperitoneally with 25 mg MAP/Kg body weight and were sacrificed at 4, 8 and 24 h. As early as 4 h after a single dose of MAP, DNA ladder bands representing DNA fragmentation into multiples of the internucleosomal DNA length of about 180 by were observed by gel electrophoresis in thymic and splenic DNA. DNA from control rats injected with 1 ml physiological saline/Kg body weight showed no ladder band patterns. The proportion of fragmented DNA from the thymus increased in a time-dependent manner up to 8 h and faint ladder band patterns were observed at 24 h, indicating that cell death via apoptosis occurred at an early stage and then apoptotic bodies were scavenged. DNA fragmentation in the thymus and spleen induced with MAP was also confirmed by the terminal deoxynucleotidyl transferase-mediated dUTPbiotin nick end labeling (TUNEL) method in situ. In control thymus samples, stained cells were numerous in the cortex but sparse in the medulla. At the boundary area between the cortex and medulla, stained cells were seen as a layer. In the MAP-treated rats, stained cells were increased and dispersed equally in the cortex and medulla. In control spleen samples, stained cells were numerous in all areas excluding the germinal centers. Cells at the germinal centers were stained intensively in MAP-treated rat spleen. Light microscopical analyses allowed us to identify lymphocytes during the course of apoptotic cell death. Electron microscopic studies showed morphological landmarks for the process of cellular apoptosis in both organs e.g. lymphocytes with chromatin condensed into crescents at the periphery of the nuclei and apoptotic bodies. These results indicate that MAP induced cell death of the thymic and splenic lymphocytes via apoptosis.
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Minds and machines 6 (1996), S. 463-480 
    ISSN: 1572-8641
    Keywords: Human reasoning ; evolution ; deontic reasoning ; transitive reasoning ; non-human primates ; neocortical ratio ; dominance hierarchy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science , Philosophy
    Notes: Abstract Research from ethology and evolutionary biology indicates the following about the evolution of reasoning capacity. First, solving problems of social competition and cooperation have direct impact on survival rates and reproductive success. Second, the social structure that evolved from this pressure is the dominance hierarchy. Third, primates that live in large groups with complex dominance hierarchies also show greater neocortical development, and concomitantly greater cognitive capacity. These facts suggest that the necessity of reasoning effectively about dominance hierarchies left an indelible mark on primate reasoning architectures, including that of humans. In order to survive in a dominance hierarchy, an individual must be capable of (a) making rank discriminations, (b) recognizing what is forbidden and what is permitted based one's rank, and (c) deciding whether to engage in or refriin from activities that will allow one to move up in rank. The first problem is closely tied to the capacity for transitive reasoning, while the second and third are intimately related to the capacity for deontic reasoning. I argue that the human capacity for these types of reasoning have evolutionary roots that reach deeper into our ancestral past than the emergence of the hominid line, and the operation of these evolutionarily primitive reasoning systems can be seen in the development of human reasoning and domain-specific effects in adult reasoning.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Minds and machines 6 (1996), S. 481-505 
    ISSN: 1572-8641
    Keywords: Neuroscience ; evolutionary psychology ; interfield theory ; evolution ; teleology ; function ; functionalism ; brain mapping ; language processing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science , Philosophy
    Notes: Abstract The idea of integrating evolutionary biology and psychology has great promise, but one that will be compromised if psychological functions are conceived too abstractly and neuroscience is not allowed to play a contructive role. We argue that the proper integration of neuroscience, psychology, and evolutionary biology requires a telelogical as opposed to a merely componential analysis of function. A teleological analysis is required in neuroscience itself; we point to traditional and curent research methods in neuroscience, which make critical use of distinctly teleological functional considerations in brain cartography. Only by invoking teleological criteria can researchers distinguish the fruitful ways of identifying brain components from the myriad of possible ways. One likely reason for reluctance to turn to neuroscience is fear of reduction, but we argue that, in the context of a teleological perspective on function, this concern is misplaced. Adducing such theoretical considerations as top-down and bottom-up constraints on neuroscientific and psychological models, as well as existing cases of productive, multidisciplinary cooperation, we argue that integration of neuroscience into psychology and evolutionary biology is likely to be mutually beneficial. We also show how it can be accommodated methodologically within the framework of an interfield theory.
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 102-108 
    ISSN: 1432-1912
    Keywords: Key words Cell cycle pause ; Apoptosis ; Berberine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In determining the morphological appearance of Balb/c 3T3 cells from berberine-treated (100 and 200 μg/ml) cultures by light microscopy demonstrated that the high berberine concentration (200 μg/ml) treatment was associated with the accumulation of numerous apoptotic cells, as identified by condensed nuclei and decrease in cell size. On the other hand, accumulation of cells in G2/M phase instead of induction of apoptosis was observed after 48–72 h of 100 μg/ml berberine treatment. Berberine was found mainly in cytoplasm during berberine-induced (100 μg/ml) cell cycle G2/M arrest, while it was highly concentrated in nuclei in the induction of apoptosis under high dose of berberine (200 μg/ml) treatment. Further addition of berberine (100–200 μg/ml) had little effect on the induction of apoptosis in the cells that had already been exposed to 100 μg/ml of berberine for 48 h. Our results suggest that there may exist in Balb/c 3T3 cells an important threshold for regulation of cell cycle pause and induction of apoptosis, that is dose-dependent.
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  • 19
    ISSN: 1432-0843
    Keywords: Key words NC-190 ; Topoisomerase II ; Cleavable complex ; DNA intercalation ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A novel benzophenazine derivative, NC-190, is a potent antitumor compound. NC-190 has been shown to inhibit the DNA strand-passing activity of DNA topoisomerase II. We investigated further the mode of action of NC-190 against DNA topoisomerase II and DNA fragmentation. NC-190 inhibited the decatenation activity of purified topoisomerase II, but had only a weak inhibitory effect against topoisomerase I. A topoisomerase II-dependent DNA cleavage assay showed that NC-190 inhibited the enzyme activity by stabilizing a topoisomerase II–DNA cleavable complex. NC-190 induced growth inhibition, protein-linked DNA breaks, and DNA fragmentation in cultured HL-60 cells in a dose-dependent manner. These activities of NC-190 in HL-60 cells were comparable to those of etoposide (VP-16). These results demonstrate a good correlation among growth inhibition, topoisomerase II-dependent DNA cleavage, and DNA fragmentation induced by NC-190. A DNA unwinding assay showed that NC-190 had intercalating activity, but its activity appeared to be weaker than those of ethidium bromide and adriamycin. These results indicate that the mechanism by which NC-190 exhibits antitumor activity may be the inhibition of topoisomerase II.
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 428 (1996), S. 165-176 
    ISSN: 1432-2307
    Keywords: Foreign-body giant cells ; Granulation tissue ; Apoptosis ; Ultrastructure ; p53 expression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To elucidate the role of apoptosis in the disappearance of multinucleated giant cells from the granulation tissue in cases of foreign-body granuloma, we induced a foreign-body reaction by implanting a collagen sponge into the dorsum of the rat and observed apoptotic changes within the multinucleated giant cells using electron microscopy. Two types of multinucleated giant cells were identified presenting apoptotic characteristics morphologically. One was characterized by apoptosis of only one nucleus, followed by cytoplasmic changes, rupture of the plasma membrane and necrosis evoking an inflammatory reaction. The other showed typical apoptotic changes in the majority or in all of the nuclei, followed by phagocytosis of the apoptotic syncytia. The results of the present study suggest that apoptosis occurring within only one nucleus might be triggered by overexpression of the p53 protein, because DNA abnormalities are confined to this single nucleus. In contrast apoptosis occurring simultaneously in the majority or all of the nuclei is most probably due to cell death caused by senescence.
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  • 21
    ISSN: 1432-2307
    Keywords: Salivary gland neoplasms ; Cytokines ; bcl-2 ; Apoptosis ; NK cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Certain cytokines are involved in the generation of natural killer (NK) cells and participate in the regulation of the proto-oncogene bcl-2. We aimed to study the mRNA expression of interleukin (IL) -2, IL-4 and IL-5, the composition of the tumour infiltrating lymphocytes (TIL), and the expression of bcl-2 in 14 benign and malignant human parotid tumours. T IL were predominantly composed of T lymphocytes and NK cells. We found evidence for the homing of T cells, and for generation of NK cells in the vicinity of the tumours. mRNA for IL-2 and IL-12, were identified but IL-4 mRNA was not found. The cytokine profiles and the composition of TIL of the two tumour categories were indistinguishable, suggesting that these host-response variables do not explain the differences in biological behaviour of these particular tumours. The results support a shift towards Th1 (T helper 1) cells and interferon-γ production, and that IL-12 also in vivo may play an important role in the regulatory interaction between innate resistance and adaptive immunity in tumour diseases. Most infiltrating lymphocytes showed strong expression of bcl-2; an interesting observation with regard to lymphocytic apoptosis in neoplastic diseases. The immunoreactivity fot the bcl-2 protein varied considerably between and within tumours, and almost all benign tumours showed strong bcl-2 positively whereas several of the malignant tumours showed weak or absent staining. The variable expression of bcl-2 protein suggests a different susceptibility of tumour cells to apoptosis. The results also indicate that bcl-2 cannot play a major role as protective agent in the specific apoptotic pathway induced by NK cells.
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  • 22
    ISSN: 1432-2307
    Keywords: Bax ; Bcl-2 ; Apoptosis ; Central nervous system ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bax and Bcl-2 proteins are identified as regulating molecules for programmed cell death. In the central nervous system, programmed cell death or apoptosis is considered to be an important phenomenon that is related to neuron vulnerability to a variety of toxic effects, including ischaemic insult. In this study, localization of Bax and Bcl-2 proteins was investigated in the human central nervous system using autopsy cases without any neurological disorder. Results were compared with findings in the rat. Most neurons in human cerebral cortex, basal ganglia and brain stem were positive for both Bax and Bcl-2 proteins, whereas Purkinje cells in cerebellum and neurons in hippocampal CA1, CA2 and CA3 regions were positive for Bax but negative or weakly positive for Bcl-2. Glial cells examined in all sections were negative for both proteins. Choroid plexus, ependymal cells and arachnoid villi showed positive reactivity for both proteins. A possible relationship between the localization of Bax or Bcl-2 proteins and the cell vulnerability in central nervous system is discussed.
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  • 23
    Electronic Resource
    Electronic Resource
    Springer
    De economist 144 (1996), S. 397-428 
    ISSN: 1572-9982
    Keywords: conventions ; institutions ; game theory ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Economics
    Notes: Summary This survey article starts with a game-theory interpretation of coordination problems that occur in an economy. Three types of games are discussed in which the degree of coordination versus conflict varies. It is shown that game-theoretic techniques for equilibrium selection or securing the highest pay-off outcome do not always suffice, which raises the need for exogenous information. Norms, such as conventions and institutions, may provide this information. The emergence and persistence of norms as well as the relationship between the type of game and the type of norm are discussed. After a discussion on conventions and rationality, some notions from Institutional Economics are introduced, in which institutions are explained as a way to deal with limited and costly information. Some applications are given in the last section.
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  • 24
    ISSN: 1432-0533
    Keywords: Key words Fas ; Glioblastoma ; Astrocytoma ; Apoptosis ; Necrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fas/APO-1 (CD95)-mediated apoptosis is one of the major mechanisms of programmed cell death. We have previously shown by reverse transcriptase-polymerase chain reaction that Fas is frequently expressed in malignant gliomas [Tachibana et al. (1995) Cancer Res 55: 5528–5530]. In this study, we assessed Fas expression in astrocytomas using a polyclonal anti-Fas antibody. Immunoreactivity to Fas was detected in 1 out of 9 (11%) low-grade astrocytomas (WHO grade II), 2 of 11 (18%) anaplastic astrocytomas (WHO grade III) and in 13 of 15 (87%) glioblastomas (WHO grade IV). In glioblastomas, Fas expression was almost exclusively observed in glioma cells surrounding foci of necrosis. In these perinecrotic areas, there was also an accumulation of glioma cells undergoing apoptosis, as detected by in situ nick-end labeling. This suggests that Fas-mediated apoptosis may play a role in the pathogenesis of necrosis which constitutes a histological hallmark of glioblastoma multiforme.
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  • 25
    ISSN: 1432-0568
    Keywords: Apoptosis ; Limb morphogenesis ; Growth factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The formation of the digits in amniote vertebrates is accompanied by a massive degeneration process that accounts for the disappearance of the interdigital mesenchyme. The establishment of these areas of interdigital cell death (INZs) is concomitant with the flattening of the apical ectodermal ridge (AER), but a possible causal relationship between these processes has not been demonstrated. Recent studies have shown that the function of the AER can be substituted for by implantation of beads bearing either FGF-2 or FGF-4 into the apical mesoderm of the early limb bud. According to these observations, if the onset of INZs is triggered by the cessation of the AER function, local administration of FGFs to the interdigital tissue prior to cell death should delay or inhibit interdigit degeneration. In the present study we have confirmed this prediction. Implanting Affi-gel blue or heparin beads pre-absorbed with either FGF-2 or FGF-4 into the interdigital tissue of the chick leg bud in the stages prior to cell death stimulates cell proliferation and causes the formation of webbed digits. Vital staining with neutral red confirmed an intense temporal inhibition of interdigital cell death after FGF treatment. This inhibition of interdigital cell death was not accompanied by modifications in the pattern of expression of Msx-1 or Msx-2 genes, which in normal development display a domain of expression in the interdigital tissue preceding the onset of degeneration.
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  • 26
    ISSN: 1432-0533
    Keywords: Key words AIDS ; Apoptosis ; Human ; immunodeficiency virus ; Rabies ; Neuropathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 46-year-old man was bitten by a dog in Mali; anti-rabies vaccination was incomplete. Three months later he was admitted to hospital with fever and diarrhea. Human immunodeficiency virus (HIV) serology was positive and CD4 count was 70/mm3. His status worsened rapidly with confusion hydrophobia and hypersialorrhea. Despite anti-rabies serotherapy and vaccination, he died suddenly 12 days after admission. Immunofluorescence on cerebral tissue samples established rabies encephalitis. Neuropathology showed mild encephalitis with occasional Babès nodules and rare perivascular mononuclear cuffs. Intraneuronal Negri inclusion bodies were remarkably diffuse and abundant. They were clearly demonstrated by immunocytochemistry and electron microscopy. Apoptotic neurons were identified in the brain stem and hippocampus in the vicinity of inflammatory foci. In contrast, apoptosis could not be demonstrated in non-inflammatory areas, even where Negri bodies were numerous. There was no associated HIV encephalitis or opportunistic infection. The occurrence of rabies encephalitis in AIDS represents a random association, but is probably not exceptional as rabies is endemic in many countries and the AIDS epidemic is spreading worldwide. In this case, although the incubation duration and clinical presentation were comparable to those in classical rabies, the T-cell-mediated immunosuppression may account for the weak inflammatory reaction and unusually abundant viral multiplication. This observation confirms that all those at risk for rabies, particularly immunocompromised patients, should receive complete anti-rabies treatment including vaccines and specific immunoglobulins, as soon as possible after infection.
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  • 27
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    Der Anaesthesist 45 (1996), S. 312-322 
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Sepsis ; systemic inflammatory response syndrome (SIRS) ; Zytokine ; Endotoxin ; Stickstoffmonoxid (NO) ; Endothelin-1 ; Zell-Zell-Kommunikation ; Streßgene ; Apoptose ; Key words Sepsis ; Systemic inflammatory response syndrome ; SIRS ; Cytokines ; Endotoxin ; Nitric oxide ; Endothelin-1 ; Intercellular communication ; Stress genes ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Clinical manifestations of sepsis, such as systemic inflammatory response and multiple organ dysfunction syndrome, are considered to be the results of a decompensated host defense response. If tissue injury is sufficiently severe to overwhelm local defense mechanisms, systemic activation of these essentially protective mechanisms may lead to autodestructive „host defense failure disease.“ This is not always caused by invading bacteria; sterile inflammation such as results from multiple trauma or pancreatitis can initiate a similar response. Evidence suggests that the activation of the macrophage/monocyte system that underlies the systemic inflammatory response may reflect one facet of a more generalized dysregulation of intercellular communication, as well as a dysfunction of such subcellular processes as signal transduction or stress gene expression. Alterations in signal transduction or stress gene expression can affect the host defense response to subsequent stressful events in either a negative or a positive sense. In particular, the sequential induction of acute phase and heat shock response may initiate programmed cell death, reflecting a potential molecular mechanism for the development of multiple organ dysfunction syndrome. The development of anti-inflammatory treatment strategies seems to be hampered by the discrepancy between locally protective and systemically deterimental properties of the host defense response.
    Notes: Zusammenfassung Sepsisbegriff und pathophysiologische Konzepte der Sepsis haben in den letzten Jahren einen tiefgreifenden Wandel erfahren. Im Zentrum der pathogenetischen Vorstellungen zur Entwicklung eines septischen (Mehr-) Organversagens steht heute die Fehlregulation potentiell protektiver Defensivsysteme des septischen Patienten im Sinne einer „host defense failure disease“. Initialer Auslöser der pathophysiologischen Sequenz von Ereignissen, die letztlich zur systemischen Entzündungsreaktion und Organschädigung führt, scheint die Aktivierung des unspezifischen Immunsystems mit exzessiver Produktion von Entzündungsmediatoren zu sein. Neben bakteriellen Toxinen kommen auch abakterielle Insulte wie Polytrauma oder Pankreatitis als Auslöser eines vergleichbaren Symptomenkomplexes mit Überstimulation der Monozyten und Makrophagen in Frage. Die Aktivierung des Monozyten-Makrophagensystems scheint dabei eine Facette einer generalisierten Störung der Zell-Zellkommunikation und subzellulärer Funktionen wie Signaltransduktion und Streßgenexpression zu sein. Veränderungen der Signaltransduktion wie der Genexpression können die Reaktion des Organismus auf nachfolgende Streßereignisse positiv wie negativ beeinflussen. Dieses als „priming“ bezeichnete Phänomen beeinflußt nach heutigem Verständnis wesentlich die Entwicklung eines eventuellen Organversagens („double hit“-Modell der Sepsis). Die Diskrepanz zwischen lokal protektiven Wirkungen und systemischen Auswirkungen einer Aktivierung der Defensivsysteme stellt ein besonderes Hindernis für die Entwicklung antiinflammatorischer oder immunmodulatorischer Therapien dar.
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  • 28
    ISSN: 1432-0533
    Keywords: Key words Focal ischemia ; Apoptosis ; Necrosis ; Inflammation ; T cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study we examined the time course of apoptotic cell death after photochemically induced focal ischemia of the rat cerebral cortex. For unequivocal differentiation between apoptosis and necrosis two criteria of programmed cell death were used: terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) and morphological evidence of fragmentation and marginalization of nuclei. After photothrombosis, many TUNEL-positive cells were found within the infarct region from 12 h to 3 days. By day 6 they were preferentially located in the boundary zone of the infarct, and by day 14 they had disappeared. A high proportion of TUNEL-positive cells displayed fragmentation or marginalization of their nuclei, indicating apoptosis. Neurons, but not T cells and macrophages, were apoptotic. Inflammatory infiltrates were in close contact to apoptotic neurons throughout the infarct areas at day 1 and in the boundary zone between days 2 and 6 after photothrombosis. In summary, our study shows that neuronal apoptosis after cerebral ischemia is a prolonged process to which leukocyte-derived cytokines may contribute. In contrast to autoimmune diseases of the nervous system, termination of the local inflammatory response after cerebral ischemia does not involve apoptosis.
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  • 29
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    Anatomy and embryology 194 (1996), S. 341-348 
    ISSN: 1432-0568
    Keywords: Mouse embryo ; Macrophages ; Mesonephros ; Metanephros ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The metanephric kidney develops from two tissue sources, the metanephric mesenchymal blastema and the ureteric bud epithelium. Following a complex interplay of inductive signals between these two tissues, small groups of metanephric mesenchymal cells aggregate and epithelialise to form young nephrons. As this is happening, significant numbers of cells in close proximity to the forming nephrons undergo programmed cell death or apoptosis. In this paper we investigate the clearance of developmental cell death in the mouse kidney between embryonic days 11.5 and 16.5; specifically, we address the issue of whether specialist macrophages or non-specialist neighbouring mesenchymal cells are responsible for phagocytosis and removal of dying cells. We show, using a monoclonal antibody F4/80 that specifically recognizes murine macrophages, that whenever and wherever there is cell death in the developing mesonephric or metanephric kidney there are also haemopoietically derived specialist macrophages. Moreover, in the mesonephros and from E14.5 in the metanephric kidney, we see large numbers of macrophages clearly swollen with phagocytosed apoptotic bodies. Double-labelling experiments using the DNA dye 7AAD to reveal condensed apoptotic nuclei and F4/80 to reveal macrophage plasma membranes show definitively that the majority of dying cells in the developing kidney are engulfed by macrophages.
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  • 30
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    Anatomy and embryology 193 (1996), S. 81-99 
    ISSN: 1432-0568
    Keywords: Programmed cell death ; Apoptosis ; Necrosis ; Development ; History
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Research on naturally occurring cell death is older than current opinion gives credit. More than 100 nineteenth century publications deal with it, and we review most of these. Soon after the establishment of the cell theory by Schleiden and Schwann, Carl Vogt (1842) reported cell death in the notochord and adjacent cartilage of metamorphic toads. Subsequent landmark discoveries included the massive cell death that occurs in pupating diptera (Weismann 1864), chondrocyte death during endochondral ossification (Stieda 1872), phagocytosis associated with cell death in the muscles of metamorphic toads (Metschnikoff 1883), chromatolytic (apoptotic) cell death in ovarian follicles (Flemming 1885), the reinterpretation of “Sarkoplasten” as “Sarkolyten” in metamorphic amphibia (Mayer 1886), the programmed loss of an entire population of neurons in fish embryos (Beard 1889), the death of scattered myocytes and myofibres in mammalian muscle (Felix 1889), and the death of many motor and sensory neurons in chick embryos (Collin 1906). Other lines of nineteenth century research established concepts important for understanding cell death, notably trophic interactions between neurons and their targets, and intercellular competition.
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  • 31
    ISSN: 1432-0568
    Keywords: Apoptosis ; Programmed cell death ; Olfactory system ; Embryogenesis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been previously shown that the embryonic olfactory nerve contains, in addition to glial ensheathing cells, a large population of differentiated neurons that migrate from the developing olfactory epithelium, in close association with the olfactory axon fascicles. The purpose of our study was to verify the hypothesis according to which a process of physiological cell death might be involved in the progressive disappearance of these migrating neurons that has been reported during late embryonic stages in several immunocytochemical studies. To do so, we have investigated the development of the olfactory nerve layer in rat embryos by using light and electron microscopy, with special reference to the presence of cell death processes within this structure. We have also applied the histochemical TUNEL method allowing in situ visualization of cells degenerating by apoptosis. In order to determine if neurons were present among dying cells, a procedure of double-labeling was performed by combining the DNA-specific bisbenzimide with two neuronal markers, the protein B-50/GAP-43 and the lectin Ulex europaeus I. Results brought out the precise temporal and spatial patterns of programmed cell death accompanying the morphogenesis of the olfactory nerve layer. A cell death process was observed within the olfactory nerve layer from its onset at embryonic day 13 (E13). While only few pycnotic cells were observed in E13 and E14 embryos, their number increased from E15 to reach a maximum at E16 and then diminished. Few dying cells were also observed along the olfactory axon fascicles when they penetrated the olfactory nerve layer. Degenerating cells appeared strongly TUNEL-labeled and exhibited morphological features of cell death by apoptosis. Double-labeling experiments revealed that some of the apoptotic cells were neurons. These observations indicate that apoptosis may account for the progressive decrease in the number of migrating neurons present within the embryonic olfactory nerve layer. Otherwise, a zone of massive cell death by apoptosis was observed at E14 within the nasal mesenchyme located ventrally and caudally to the olfactory nerve layer. Double-labeling experiments showed that apoptotic cells present within this zone were not neurons. Our findings strongly suggest that apoptotic cell death of migrating neurons may allow the elimination of non-functional cells whereas that of mesenchymal cells may facilitate outgrowth of the newly formed olfactory axon fascicles by pathway formation.
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  • 32
    ISSN: 1432-069X
    Keywords: Key words Photodynamic therapy ; Cisplatin ; Human ; squamous cell carcinoma cell line ; Apoptosis ; Nuclear ; matrix protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 33
    ISSN: 1432-069X
    Keywords: Key words Cultured keratinocytes ; Cisplatin ; Fas ; antigen ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 34
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    Insectes sociaux 43 (1996), S. 375-389 
    ISSN: 1420-9098
    Keywords: Nasutitermitinae ; Subulitermes ; Coatitermes ; Velocitermes ; evolution ; phylogeny
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The developmental pathways of the neuter castes were studied in three species of Nasutitermitinae from central Panama. The humivorousSubulitermes denisae andCoatitermes clevelandi display several primitive traits: absence of sex dimorphism, representation of both sexes among workers and soldiers, and occurrence of successive worker instars. The litter-dwellingVelocitermes barrocoloradensis has a more complex caste system: female larvae are larger than males and give rise to the large workers, which constitute the bulk of the work force; male larvae proceed to soldiers through a small worker or a special larval instar. The resulting soldier caste is polymorphic. These results support previously formulated hypotheses regarding a link between humivorous diet and reduced polymorphism on the one hand, and between forest-floor foraging and large continuous size variation among soldiers on the other. Whereas the caste systems ofSubulitermes andCoatitermes probably represent a primitive condition,Velocitermes shares derived traits withNasutitermes and the other fully nasute genera previously studied. I therefore hypothesize that ancestors with these advanced features may have spread from the neotropics and be at the origin of most nasute genera, including humivorous taxa, present in other regions.
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  • 35
    ISSN: 1420-9098
    Keywords: Formicidae ; Leptothoracini ; Tetramoriini ; internal transcribed spacer ; social parasitism ; evolution ; phylogenetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A fragment of the internal transcribed spacer (ITS-1) adjacent to the 5.8S rRNA gene of 20 myrmicine ant species was sequenced. Sequence comparisons were carried out between 11 species of the tribe Leptothoracini, five species of the tribe Tetramoriini, three species of the tribe Solenopsidini and one species of the tribe Myrmicini. Additionally, the formicine antCamponotus ligniperda (tribe Camponotini) was analyzed as an outgroup species. Among all investigated species, the fragment had a variable length of ≈ 230–380 bp with only a few conserved sequence elements. The sequences of this fragment were perfectly identical within four palearctic populations ofLeptothorax acervorum indicating that intraspecific variation is rather low. Within the species of Tetramoriini (includingAnergates atratulus) 94.1% of sequence positions were identical, 95.6% within the species of theLeptothorax s.str.-group and 64.6% within the species of theMyrafant-group. Phylogenetic analysis reveals that the social parasitesHarpagoxenus sublaevis, Doronomyrmex goesswaldi, D. kutteri andD. pacis, Chalepoxenus muellerianus as well asStrongylognathus alpinus andTeleutomyrmex schneideri are most closely related to the groups of their respective host species, which generally confirms the taxonomical classifications of the subfamily Myrmicinae based on morphological criteria. The taxonomical positions of the speciesA. atratulus has as yet been uncertain, however, sequence comparison of the ITS-1 fragment leads to the conclusion thatA. atratulus rather belongs to the tribe Tetramoriini than to the Solenopsidini.
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  • 36
    ISSN: 1423-0445
    Keywords: sex pheromone ; synergist ; antagonist ; mate recognition ; reproductive isolation ; chemotaxonomoy ; phylogeny ; evolution ; Lepidoptera ; Tortricidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The geometric isomers (E,E)-, (E,Z)-, (Z,E)-, and (Z,Z)-8,10-dodecadien-1-yl acetate were identified as sex pheromone components or sex attractants in the tribes Eucosmini and Grapholitini of the tortricid subfamily Olethreutinae. Species belonging to the more ancestral Tortricinae were not attracted. Each one isomer was behaviourally active in males ofCydia andGrapholita (Grapholitini), either as main pheromone compound, attraction synergist or attraction inhibitor. Their reciprocal attractive/antagonistic activity in a number of species enables specific communication with these four compounds.Pammene, as well as otherGrapholita andCydia responded to the monoenic 8- or 10-dodecen-1-yl acetates. Of the tribes Olethreutini and Eucosmini,Hedya, Epiblema, Eucosma, andNotocelia trimaculana were also attracted to 8,10-dodecadien-1-yl acetates, but several otherNotocelia to 10,12-tetradecadien-1-yl acetates. The female sex pheromones ofC. fagiglandana, C. pyrivora, C. splendana, Epiblema foenella andNotocelia roborana were identified. (E,E)- and (E,Z)-8,10-dodecadien-1-yl acetate are producedvia a commonE9 desaturation pathway inC. splendana. CallingC. nigricana andC. fagiglandana females are attracted to wingfanning males.
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  • 37
    ISSN: 1432-0843
    Keywords: Key words Rabbit ; VX2 uterine cancer ; Embolization ; Cisplatin ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of chemoembolization with cisplatin on gynecological malignancy were investigated using rabbit uterine tumors. A group of 20 rabbits were subjected to inoculation of the uterus with 5×107 VX2 carcinoma cells and 4 weeks later were divided into four groups, each consisting of five rabbits: an untreated control group, a group given cisplatin intraarterially (IA), a group subjected to transcatheter arterial embolization (TAE) with Gelfoam particles and a group subjected to transcatheter chemoembolization (TACE) with Gelfoam particles plus 1 mg/kg cisplatin. All groups were examined histologically 2 days after treatment. The untreated control group was further investigated 4 weeks after inoculation. In the untreated control group, the tumor cell nuclei varied in size and were irregular in form, and multiple nuclei and nuclear division were also observed. No necrotic zones were found up to 4 weeks after inoculation. The IA group showed no necrosis, but a few apoptotic cells were scattered throughout the tumor. In the TAE group, necrosis was observed in the center of the tumors, but proliferating cells persisted at the periphery. In the TACE group, necrosis was observed in the central part with many apoptotic cells surrounding the necrotic region in layers. The proliferating cell nuclear antigen (PCNA) index was 95.88% in the untreated control group, 86.6% in the IA group, and 8.62% in the TACE group, indicating a significant reduction in cell proliferation in the TACE group. These findings suggest that TACE results in more effective cytotoxicity than the other two treatments in uterine cancer tumor transplants.
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  • 38
    ISSN: 1432-0851
    Keywords: Key words Cytokine ; Nitric oxide ; Bcl-2 ; Apoptosis ; Tumor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Cytokine-mediated cell death in tumor cells can be achieved through endogenous nitric oxide (NO) from within tumor cells or exogenous NO from either activated macrophages or endothelial cells. The purpose of this study was to determine the role of Bcl-2 in NO-mediated apoptosis. The incubation of murine L929 and NIH3T3 cells with interleukin-1α (IL-1α) and interferon γ (IFNγ) induced high endogenous NO production only in the L929 cells that also underwent apoptosis. NIH3T3 cells were not resistant to NO-mediated apoptosis. In fact, the incubation of L929 and NIH3T3 cells with exogenous NO derived from NO donors, sodium nitroprusside, or S-nitroso-N-acetyl-DL-penicillamine (SNAP) induced death, characterized by typical apoptotic morphology and DNA fragmentation, in both cell types, but to a higher degree in NIH3T3 cells than in the L929 cells. We then measured the effect of Bcl-2 expression on exogenous NO-induced apoptosis. At both the mRNA and protein levels, L929 fibroblasts expressed higher levels of endogenous mouse Bcl-2 than did NIH3T3 cells. At the same time, L929 cells were much more resistant to exogenous NO-induced cell death than were NIH3T3 cells. The inverse correlation between mouse Bcl-2 expression and sensitivity to exogenous NO-mediated cell death was also found in the murine K-1735 melanoma C-23 and X-21 clonal populations. Transfection of both NIH3T3 cells and L929 cells with the human bcl-2 gene led to resistance to both exogenous and endogenous NO-mediated apoptosis. These data demonstrate that NO-mediated apoptosis can be suppressed by expression of Bcl-2, suggesting that abnormal expression of Bcl-2 may influence the efficacy of tumor immunotherapy.
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  • 39
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    Journal of cancer research and clinical oncology 122 (1996), S. 166-170 
    ISSN: 1432-1335
    Keywords: Apoptosis ; Colon cancer ; In situ nick-ended DNA labeling ; p53 ; bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of apoptosis in colon cancer was investigated in terms of control of growth and expression of p53, using the nick-ended-DNA labelling method and immunohistochemistry. The apoptotic labeling index was highest in the T1 stage (24 cases), as was the proliferative activity, assessed in terms of the Ki-67 labeling index. Both labeling indices demonstrated similar overall incidence curves for the total 95 colon cancer cases, and examination of individual cases revealed a statistically significant correlation (P=0.01). However, neither index had any relation to p53. The results thus suggest that apoptosis in colon cancers has a linkage with proliferative activity that can be assessed by Ki-67 labeling, but is not regulated by the p53 system. This might contribute to the diversity of colon cancer growth.
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  • 40
    ISSN: 1432-1335
    Keywords: Apoptosis ; Paclitaxel ; Squamous-cell carcinoma cell line ; Time-lapse video microscopy ; Head and neck cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Paclitaxel (Taxol) is a potent chemotherapeutic drug for squamous-cell carcinoma (SCC) of the head and neckin vitro with microtubule-stabilizing activity that arrests cells in G2-M. To study the mechanism of its cytotoxic effect on SCCin vitro, we exposed five laryngeal SCC cell lines to 10 nM paclitaxel. The cell lines were studied by time-lapse video microscopy for 96 h, and by agarose gel electrophoresis. Paclitaxel blocked the cells in the premitotic phase for 6–24 h, after which the cells died morphologically by apoptosis. Mitotically arrested cells were seen within a few minutes after exposure to paclitaxel. No mitoses were seen in the paclitaxel-treated cells. A few apoptoses were also seen in the control cultures grown without paclitaxel, but they represented only 6%–20% of the frequency of apoptoses seen in the paclitaxel-treated group. In some paclitaxel-treated cultures the cells escaped the mitotic arrest without cytokinesis and formed multinucleated cells that eventually died. Agarose gel electrophoresis showed oligonucleosomal DNA fragmentation characteristic of apoptosis. We conclude that time-lapse video microscopy is an efficient method of observing drug-induced morphological changes in cell culture. Paclitaxel at a 10 nM concentration rapidly induces a premitotic block, which usually leads to apoptotic cell death. In some cases multinucleated cells are formed that morphologically also eventually die by apoptosis.
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  • 41
    ISSN: 1432-1173
    Keywords: Schlüsselwörter Systemischer Lupus erythematodes ; Endogene Retroviren ; UV-Strahlung ; Apoptose ; Key words Systemic lupus erythematosus ; Endogenous retrovirus ; UV-light ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Endogenous retroviral sequences (ERV) are integrated parts of the human genome. They make up at least 1% of the total genomic DNA. This pool of genetic material might help explain the long discussed role of retroviruses in autoimmune disease. Their proviral features suggest two possible models leading to autoimmune disease: the mobile insertion into a or near a somatic gene, changing its function, and the expression of proteins by ERV, which then might act as autoantigens or superantigens. These mechanisms are supported by prior studies of systemic lupus erythematosus (SLE). In MRL-lpr/lpr mice with SLE-like disease the insertion of a mobile retroviral element, the early transposon (ETn), into the second intron of the fas gene leads to reduced apoptosis, accumulation of lymphocytes and earlier mortality. Investigations of murine and human SLE demonstrate autoantibodies against self-proteins, which crossreact with retroviral proteins. Future investigations may further establish the interrelation between the activation of endogenous retroviral sequences and SLE with its multifactorial genetic determinants.
    Notes: Zusammenfassung Endogene retrovirale Sequenzen (ERV) sind integrierte Bestandteile der Erbsubstanz und stellen wenigstens 1% der gesamten genomischen DNA des Menschen dar. Dieses Reservoir an genetischer Information könnte eine Erklärung für die seit langem diskutierte Rolle von Retroviren in der Pathogenese von Autoimmunerkrankungen sein. Durch ihre Eigenschaften als eine Art Provirus sind dabei heute zwei Modelle der Pathogenese vorstellbar, einerseits die mobile Insertion von ERV in ein Wirtsgen oder nahe diesem und damit dessen Funktionsänderung, andererseits die Expression von endogenen retroviralen Proteinen, welche als Autoantigen oder Superantigen fungieren können. Für beide Modelle gibt es bereits beim systemischen Lupus erythematodes (SLE) experimentell belegte Zusammenhänge. Im Genom von MRL-lpr/lpr Mäusen mit einer SLE-ähnlichen Erkrankung findet sich die Insertion eines mobilen retroviralen Elements im zweiten Intron des Fas-Gens. Dies führt zu reduzierter Apoptose, Lymphozytenakkumulation und erhöhter früher Mortalität der Mäuse. Bei murinem und humanem SLE weisen Autoantikörper gegen körpereigene Proteine eine Kreuzreaktivität mit retroviralen Proteinbestandteilen auf. Zukünftige Untersuchungen auf diesem Gebiet könnten Zusammenhänge zwischen einer Aktivierung endogener retroviraler Sequenzen und der genetisch multifaktoriell bedingten Erkrankung SLE aufzeigen.
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  • 42
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    Der Pathologe 17 (1996), S. 405-416 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Systemischer Lupus erythematosus ; DNA-Hypomethylierung ; Integrinüberexpression ; Apoptose ; Nucleosom-Antikörper ; Antiphospholipidsyndrom ; β2-Glykoprotein 1 ; Key words Systemic lupus erythematosus ; DNA hypomethylation ; Integrin overexpression ; Apoptosis ; Nucleosome antibody ; Antiphospholipid syndrome ; β2-Glycoprotein 1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by the synthesis of antinuclear antibodies. Nucleosomes – the disc-like structural units of chromatin, composed of histones and DNA – are the primary antigenic structure that induces the formation of complement-activating antigen-antibody complexes in basement membranes. The autoreactivity in SLE has been elucidated in drug-induced SLE: hypomethylation of DNA leads to overexpression of integrin CD11a/CD18, increased binding of T-cells to macrophages and B-cells, a higher rate of apoptosis of macrophages, and elevated B-cell activity with consecutive production of autoantibodies. Disturbances of apoptosis (e. g. mutation of Fas gene) are relevant also in non-drug-induced SLE. The morphologic diagnosis – by light microscopy, immunohistology and electron microscopy – of skin and renal biopsies can confirm the diagnosis and help in prognostic assessment as well as therapeutic decisions in SLE. The value of the morphologic diagnosis in SLE is enhanced by reporting semiquantitative scores of disease activity and chronicity. The antiphospholipid syndrome (APS) is characterized by thrombosis, thrombocytopenia, recurrent fetal loss and antiphospholipid antibodies. APS associated with SLE or other systemic autoimmune diseases has been termed secondary APS. Antibodies in APS are directed against phospholipids and phospholipid-protein complexes. One of these proteins is β2-glycoprotein 1. An important mechanism of the increased rate of thrombosis in APS is probably the inhibition of the protein C-catalyzed inactivation of clotting factors V and VIII. Venous thrombosis with recurrent pulmonary emboli and arterial thrombi in brain, heart and kidney (thrombotic microangiopathy) can lead to divergent clinical manifestations in APS.
    Notes: Zusammenfassung Der systemische Lupus erythematosus (SLE) ist eine Autoimmunerkrankung, die durch die Synthese antinukleärer Antikörper gekennzeichnet ist. Nucleosomen, bestehend aus Histonen und DNA, sind die primäre antigene Struktur, die zur Bildung komplement-aktivierender Antigen-Antikörperkomplexe an Basalmembranen führt. Die Autoreaktivität ist beim Medikamenten-induzierten SLE durch eine Hypomethylierung von DNA, Überexpression von Integrin CD11a/CD18, übermäßige Bindung von T-Zellen an Makrophagen und B-Zellen, eine Apoptose von Makrophagen und gesteigerte B-Zellaktivität mit Produktion von Autoantikörpern bedingt. Störungen der Apoptose (z. B. Mutation des Apoptose-1- (Apo1-) oder Fas Gens) sind offenbar auch beim nicht-pharmaka-induzierten SLE bedeutsam. Die lichtmikroskopische, immunhistologische und ultrastrukturelle Diagnostik von Haut- und Nierenbiopsien kann zur Diagnosesicherung, Abschätzung von Prognose und zur Therapieentscheidung beim SLE wesentlich beitragen, insbesondere wenn semiquantitative Aktivitäts- und Chronizitätsscores ermittelt werden. Das Antiphospholipidsyndrom (APS) ist durch Thrombosen, Thrombozytopenie, rekurrierende Aborte und Antiphospholipid-Antikörper charakterisiert. Ein APS bei SLE und anderen Systemerkrankungen wird als sekundäres APS bezeichnet. Antikörper beim APS sind gegen Phospholipide und Phospholipid-/Proteinkomplexe gerichtet. Ein komplexierendes Protein ist β2-Glykoprotein 1. Ein wichtiger Mechanismus der erhöhten Thromboserate ist wahrscheinlich eine Hemmung der Protein C vermittelten Inaktivierung der Gerinnungsfaktoren V und VIII. Venöse Thrombosen mit rezidivierenden Lungenarterienembolien und arterielle Thrombosen in Gehirn, Herz und Niere (thrombotische Mikroangiopathie) führen zu sehr differenten klinischen Manifestationen.
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  • 43
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    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 102-108 
    ISSN: 1432-1912
    Keywords: Cell cycle pause ; Apoptosis ; Berberine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In determining the morphological appearance of Balb/c 3T3 cells from berberine-treated (100 and 200 μg/ml) cultures by light microscopy demonstrated that the high berberine concentration (200 μg/ml) treatment was associated with the accumulation of numerous apoptotic cells, as identified by condensed nuclei and decrease in cell size. On the other hand, accumulation of cells in G2/M phase instead of induction of apoptosis was observed after 48–72 h of 100 μg/ml berberine treatment. Berberine was found mainly in cytoplasm during berberine-induced (100 μg/ml) cell cycle G2/M arrest, while it was highly concentrated in nuclei in the induction of apoptosis under high dose of berberine (200 μg/ml) treatment. Further addition of berberine (100–200 μg/ml) had little effect on the induction of apoptosis in the cells that had already been exposed to 100 μg/ml of berberine for 48 h. Our results suggest that there may exist in Balb/c 3T3 cells an important threshold for regulation of cell cycle pause and induction of apoptosis, that is dose-dependent.
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  • 44
    ISSN: 1432-0738
    Keywords: Key words Phocomelia ; Cyclophosphamide ; Apoptosis ; Mouse fetus ; Limb buds
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Phocomelia (absence of upper fore and/or hind limbs) was induced in mouse fetuses using cyclophosphamide. On day 11 of gestation, pregnant mice were injected intraperitoneally with 10 ml/kg of saline containing cyclophosphamide (CP) at a dosage of 20 mg/kg body weight. On day 18, the fetuses were removed by Caesarean section from dams given CP on day 11 and were examined for external anomalies. Of 22 fetuses from CP-treated dams, 13 were dead or absorbed, but the surviving 9 fetuses were found to have phocomelia with various other external anomalies. In order to examine the direct cytotoxic effect of CP on fetal limb buds, fetuses were removed at 8, 16, 24, and 48 h after CP administration on day 11, revealing the presence of frequent pyknotic nuclei and apoptotic bodies in hematoxylin and eosin (H & E) preparations. Cell-nuclei and apoptotic bodies were frequently observed by nick end-labeling in limb buds. Transmission electron microscopy demonstrated the typical changes of apoptosis. DNA extracted from the fetal limb buds submitted to CP was analysed by agarose gel electrophoresis, showing the ladder pattern characteristic of internucleosomal cleavage. These findings suggest that cyclophosphamide causes apoptosis in mouse fetal limb buds and that this process induces the external anomalies of phocomelia.
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  • 45
    ISSN: 1432-0738
    Keywords: Key words Arsenic compounds ; Dimethylarsinic acid ; Apoptosis ; Glutathione
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Inducibility of apoptosis in cultured human HL-60 cells by arsenic compounds, such as arsenite, arsenate, methylarsonic acid (MAA), and dimethylarisinic acid (DMAA), was investigated, together with the role of glutathione (GSH) in the induction. Among the arsenic compounds DMAA was the most potent in terms of the ability to cause the morphological changes (formation of nuclear fragmentation and apoptotic bodies) characteristic of apoptosis. Furthermore, fragmentation of internucleosomal DNA was also induced by DMAA. Depletion of cell GSH by L-buthionine-SR-sulfoximine, a selective inhibitor of γ-glutamylcysteine synthetase, enhanced the cytotoxicity of arsenite, arsenate, and MAA, while such depletion suppressed the cytotoxicity of DMAA. The depletion of GSH also suppressed the morphological changes and the fragmentation of internucleosomal DNA caused by DMAA, both of which are characteristic features of apoptosis. The results suggest that the death of cells caused by DMAA is due to apoptosis and that GSH is involved in the induction of apoptosis by this arsenic compound.
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  • 46
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    Archives of toxicology 70 (1996), S. 249-251 
    ISSN: 1432-0738
    Keywords: Key words Fluoride ; Alveolar macrophages ; Cytotoxicity ; Apoptosis ; DNA fragmentation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Since inhaled fluoride is implicated in the acute respiratory failure, cytotoxic effects of fluoride on alveolar macrophages, primary target cells of inhaled toxicants, were investigated. The LC50 of sodium fluoride was estimated to be 0.41 mM, while 1 mM sodium chloride, bromide and iodide had virtually no effects on the viability of alveolar macrophages. Photomicroscopic observation revealed that nuclei of the fluoride-exposed alveolar macrophages were fragmented. The ladder formation was observed when DNA isolated from fluoride-exposed alveolar macrophages was electrophoresed in agarose gel. These results suggest that cytotoxicity of fluoride is associated with apoptosis in rat alveolar macrophages.
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  • 47
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    Journal of cancer research and clinical oncology 122 (1996), S. 383-396 
    ISSN: 1432-1335
    Keywords: Antihormones ; Total receptor blockade ; Ligand-independent activation ; Receptor gene amplification and mutation ; Differentiation ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Endocrine therapy of mammary and prostate cancer has been established for decades. The therapies available to block sex-hormone-receptor-mediated tumor growth are based on two principles: (i) ligand depletion, which can be achieved surgically, by use of luteinizinghormone-releasing hormone analogues or inhibitors of enzymes involved in steroid biosynthesis or by interfering with the feedback mechanisms of sex hormone synthesis at the pituitary/hypothalamic level; (ii) blockade of sex hormone receptor function by use of antihormones. The antiestrogen tamoxifen, which is the compound of choice for the treatment of mammary carcinoma, has the drawback of being a partial agonist. A complete blockade of estrogen receptor (ER) function can be achieved by a new class of compounds, pure antiestrogens. In contrast to aromatase inhibitors, pure antiestrogens are able to block ER activation by ligands other than estradiol and can also interfere with ligand-independent ER activation. In addition to estradiol, progesterone has a strong proliferative effect in mammary carcinomas. Antiprogestins are promising new tools for clinical breast cancer therapy. These compounds clearly need a functionally expressed progesterone receptor to block tumor growth, but there is strong experimental evidence that their tumor inhibition is based on more than just progesterone antagonism. The ability of these compounds to induce tumor cell differentiation that leads to apoptosis is unique among all other endocrine therapeutics. In prostate tumors that have relapsed from current androgen-ablation therapies the androgen receptor (AR) is still expressed and, compared to the primary tumors, its level is often even enhanced. Mutated AR that can be activated by other compounds such as adrenal steroids, estrogens, progestins and even antiandrogens have been detected in recurrent tumors. Thus, relapse of tumors under the selective pressure of common androgen-ablation therapies can be caused by acquired androgen hypersensitivity and AR activation by ligands other than (dihydro-)testosterone. There is a clinical need for future compounds that produce a complete blockade of AR activity even in recurrent tumors. Preclinical experiments indicate that combination therapy as well as the extension of endocrine treatments to several other tumor entities are promising approaches for further developments. Examples are the combination of antiestrogens and antiprogestins for breast cancer treatment, or the treatment of prostate carcinomas with antiprogestins.
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  • 48
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    Journal of cancer research and clinical oncology 122 (1996), S. 319-327 
    ISSN: 1432-1335
    Keywords: Gene targeting ; Mouse knockouts ; Tumor-suppressor genes ; Cancer genetics ; Apoptosis ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The use of the mouse as a model organism in cancer research has a long and productive history, from the earliest studies of chemical carcinogenesis to the recent advances in gene targeting. Many of the basic principles of tumorigenesis have been formed in whole or in part through the study of tumor development in the mouse. Over the past decade, the major experimental approach has been to generate cancer-prone strains, either through transgenic technologies or, more recently, gene targeting. Here, I will review the state of the field of gene targeting of tumor-suppressor genes and concentrate on thep53 mutant strains and the lessons learned from thep53 mutant mouse.
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  • 49
    ISSN: 1432-1335
    Keywords: p53 ; Chemoradiosensitivity ; Apoptosis ; Gastric cancer ; Colorectal cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We previously reported that introduction of the wild-typep53 gene into human cancer cells with deletedp53 enhanced apoptosis induced by chemotherapy [Fujiwara et al. (1994) Cancer Res 54∶2287]. This suggests thatp53 status could be a potent determinant of the therapeutic efficacy of DNA-damaging cancer therapy. We analyzed 24 patients with gastric or colorectal cancer forp53 mutations and apoptotic changes in surgical specimens. Out of 11 patients with gastric cancer, 3 were treated with chemotherapeutic drugs before resection; 5 of 13 patients with colorectal cancer had 30 Gy radiation prior to surgery.p53 mutations were detected in 4 cases of gastric cancer (36.4%) and in 6 cases of colorectal cancer (46.2%) by immunohistochemical staining. The preoperative DNA-damaging therapies increased the number of apoptotic cells in wild-type-p53-expressing tumors; tumors with mutantp53, however, significantly showed fewer apoptotic cells compared with those expressing wild-typep53. Thep53-inducible WAF1/CIP1 protein was immunohistochemically observed in wild-type-p53-containing tumors, where-as mutant-p53-expressing tumors expressed no detectable WAF1/CIP1. Taken together, we conclude thatp53 mutations are associated with the poor response of chemotherapy and radiotherapy.
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  • 50
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    European archives of psychiatry and clinical neuroscience 246 (1996), S. 137-146 
    ISSN: 1433-8491
    Keywords: Alzheimer's dementia ; Clinicopathological correlations ; Neurofibrillary tangles ; Senile plaques ; Pathogenesis ; Synapse Poss ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Quantitative clinicopathological correlation studies are one way to address the question of the relevance of morphological abnormalities in Alzheimer's dementia (AD). This paper summarizes results of the Vienna Longitudinal Study on Dementia obtained during the past few years and presents a critical discussion on the relevance of clinicopathological correlation studies for the pathogenesis of AD. Plotting of psychometric test scores against the numbers of plaques, tangles and neuropil threads in various cortical areas shows that significant correlations are due primarily to very high lesion counts in severely demented patients. These data indicate that neocortical neurofibrillary pathology can be considered an end-stage marker in the pathology of AD. On the other hand, the topographical staging of neuritic Alzheimer changes proposed by Braak and Braak (1991) appears to be a better reflection of the progression of the degenerative process than numerical lesion counts; there is a linear correlation between the Braak stages and Mini-Mental State scores in 122 aged individuals. Significant correlations are further obtained between the severity of dementia and the levels of a number of synaptic proteins including synaptophysin and the chromogranins. Taken together, our data suggest that none of the classical AD lesions, plaques and tangles, play a central role in the pathogenesis of dementia, a fact that is supported by a molecular biological study showing that there is no close relationship between these lesions and the neurons undergoing degeneration in AD. Whereas neuritic pathology is a useful histopathological marker for the diagnosis and staging of AD, the major correlate of cognitive deficits is the loss of corticocortical and subcorticocortical connections reflected by a depletion of synapses. This pathology may be induced by a mismetabolism of the β-amyloid precursor proteins or their interaction with cytoskeletal proteins related to neuronal degeneration.
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  • 51
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    Journal of industrial microbiology and biotechnology 17 (1996), S. 151-158 
    ISSN: 1476-5535
    Keywords: bacteriocins ; colicins ; evolution ; ecology ; Escherichia coli
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract In this review we focus on the ecological and evolutionary forces that determine the frequency and diversity of colicins inEscherichia coli. To begin, we describe that this killing phenotype is ubiquitous inE. coli, with as many as 50% of the isolates from a population producing colicin toxins, and that each population sampled has its own unique distribution of the more than 20 known colicin types. Next, we explore the dynamics of colicinogeny, which exhibits a typical form of frequency dependence, where the likelihood of successful colicin invasion into a population increases as the initial density of colicinogenic cells increases. We then incorporate thoughts on the evolution of chromosomal resistance to colicins and describe how resistance might influence the dynamics of colicinogen invasion and maintenance and the resulting colicin diversity. The final section deals with a genetic and phylogenetic characterization of colicins and a discussion of the evolutionary mechanisms responsible for generating colicin diversity. In this final section we provide details of the different molecular mechanisms known to play a role in generating colicin diversity, including the two most dominant forces in colincin evolution: recombination and positive, deversifying, selection.
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  • 52
    ISSN: 1573-1561
    Keywords: Sex pheromone ; Idaea aversata ; Idaea straminata ; Idaea biselata ; (Z,Z)-9,11-tetradecadienyl acetate ; (Z,Z)-7,9-dodecadienyl acetate ; (Z,E)-7,9-dodecadienyl acetate ; Lepidoptera ; Geometridae ; electroantennography ; single cell recording ; biosynthesis ; phylogeny ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Pheromone compounds so far identified from most geometrid moths consist of all-Z diene, triene, or tetraene hydrocarbons with chain lengths of C17 to C21, and their monoepoxide derivatives biosynthesized from linoleic and linolenic acids. The present study reports the occurrence of olefinic acetates as sex pheromones in three species of Geometridae. (Z,Z)-9,11-tetradecadienyl acetate and (Z,Z)-7,9-dodecadienyl acetate found in female gland extracts ofIdaea aversata elicited significant responses from conspecific male antennae in gas chromatography with electroantennographic detection (GCEAD). In extracts ofI. straminata, (Z,Z)-7,9-dodecadienyl acetate, (E,Z)-7,9-dodecadienyl acetate, and (Z,Z)-7,9-dodecadienyl acetate were found, and the synthetic compounds elicited strong responses from conspecific male antennae. In the third species,I. biselata, only (Z,Z)-7,9-dodecadienyl acetate was found in the female extracts, and this compound elicited a strong EAD response from the conspecific male antenna. The identities of the pheromone components inI. aversata andI. straminata were further confirmed according to their characteristic ions after GC-MS analyses. Single sensillum recordings fromI. aversata showed two types of pheromone-detecting sensilla present on the male antenna. One type contained two receptor neurons, one of which was specifically tuned to (Z,Z)-9,11-tetradecadienyl acetate, the other to (Z,E)-9,11-tetradecadienyl acetate. A second type contained one neuron responding to (Z,Z)-7,9-dodecadienyl acetate. The two types were clearly different also with respect to external morphology, the former being considerably longer and having a larger base diameter. Also inI. straminata two physiological types of sensilla could be distinguished. One type contained two neurons, one of which responded to (Z,Z)-7,9-dodecadienyl acetate, the other to (Z,E)-9,11-tetradecadienyl acetate. The second type contained one neuron, responding to (Z,Z)-7,9-dodecadienyl acetate. No correlation between external morphology and physiological response of the investigated sensilla was observed inI. straminata. In field tests, a two-component blend containing (Z,Z)-9,11-tetradecadienyl acetate and (Z,Z)-7,9-dodecadienyl acetate in a ratio of 10:1 was attractive to males ofI. aversata. This two-component blend was also attractive to males ofI. straminata, but in a ratio of 1:1. High numbers of maleI. biselata were caught in traps baited with (Z,Z)-7,9-dodecadienyl acetate alone. The incorporation of deuterium labels into pheromone components after topical application of deuterium-labeled palmitic acid confirmed that the pheromone components ofI. aversata could be synthesized from this precursor, as has been previously observed for acetate pheromone components of many other moth species. Our results suggest that an evolutionary reversal back to the production of palmitic acid-derived pheromone components has occurred within the geometrid subfamily Sterrhinae.
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  • 53
    ISSN: 1573-4919
    Keywords: guanine nucleotide-binding proteins ; evolution ; phylogeny ; structure-function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract ADP-ribosylation factors (ARFs) are ∼20-kDa guanine nucleotide-binding proteins that are allosteric activators of the NAD:arginine ADP-ribosyltransferase activity of cholera toxin and appear to play a role in intracellular vesicular trafficking. Although the physiological roles of these proteins have not been defined, it has been presumed that each has a specific intracellular function. To obtain genetic evidence that each ARF is under evolutionary pressure to maintain its structure, and presumably function, rat ARF cDNA clones were isolated and their nucleotide and deduced amino acid sequences were compared to those of other mammalian ARFs. Deduced amino acid sequences for rat ARFs 1, 2, 3, 5 and 6 were identical to those of the known cognate human and bovine ARFs; rat ARF4 was 96% identical to human ARF4. Nucleotide sequences of both the untranslated as well as the coding regions were highly conserved. These results indicate that the ARF proteins are, as a family, extraordinarily well conserved across mammalian species. The unusually high degree of conservation of the untranslated regions is consistent with these regions having important regulatory roles and that individual ARFs contain structurally unique elements required for specific functions.
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  • 54
    ISSN: 1573-4935
    Keywords: Chemotaxis ; evolution ; oligopeptides ; Tetrahymena ; Dunaliella
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Chemotactic properties of amino acids (L-alanine, glycine and L-lysine) and their oligopeptides (10−6M) and binding sites to these ligands were investigated in two unicellular models, the heterotrophicTetrahymena pyriformis and the auxotrophicDunaliella salina. Chemotaxis ofDunaliella induced by simple amino acids and their derivatives demonstrated that binding sites (receptors) for food molecules are not only present in the membrane but are also able to induce their basic physiological response. InTetrahymena, substances with special molecular structure and properties (polar, hydrophilic character of the signal peptide chain)-5-L-Lys, 5-Glywere required for chemoattraction, other peptides tested, lacking the required structure, were repellent. Divergences in chemotaxis and binding assays of both species suggest that trends of functional and binding parameters do not run parallel at this level of evolution.
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  • 55
    ISSN: 1573-5028
    Keywords: carbon fixation ; chloroplasts ; evolution ; isoenzymes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A cDNA encoding the Calvin cycle enzyme transketolase (TKL; EC 2.2.1.1) was isolated from Sorghum bicolor via subtractive differential hybridization, and used to isolate several full-length cDNA clones for this enzyme from spinach. Functional identity of the encoded mature subunit was shown by an 8.6-fold increase of TKL activity upon induction of Escherichia coli cells that overexpress the spinach TKL subunit under the control of the bacteriophage T7 promoter. Chloroplast localization of the cloned enzyme is shown by processing of the in vitro synthesized precursor upon uptake by isolated chloroplasts. Southern blot-analysis suggests that TKL is encoded by a single gene in the spinach genome. TKL proteins of both higher-plant chloroplasts and the cytosol of non-photosynthetic eukaryotes are found to be unexpectedly similar to eubacterial homologues, suggesting a possible eubacterial origin of these nuclear genes. Chloroplast TKL is the last of the demonstrably chloroplast-localized Calvin cycle enzymes to have been cloned and thus completes the isolation of gene probes for all enzymes of the pathway in higher plants.
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  • 56
    ISSN: 1573-4927
    Keywords: Bubalus ; tamaraw ; anoa ; cytochromeb ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The cytochromeb genes of all living species ofBubalus, including the river type and the swamp type of domestic buffaloes (Bubalus bubalis), were sequenced to clarify their phylogenetic relationships. These sequences were compared together with the African buffalo (Syncerus caffer) and banteng (Bos javanicus) sequences as an outgroup. Phylogenetic trees ofBubalus species based on the DNA sequences of the cytochromeb gene demonstrated that the tamaraw (Bubalus mindorensis), endemic to the Philippines, could be classified into the subgenusBubalus, not the subgenusAnoa. The divergence time between the lowland anoa (B. depressicornis) and the mountain anoa (B. quarlesi) was estimated at approximately 2.0 million years (Myr), which is almost the same as the coalescence time for theBubalus sequences. This large genetic distance supports the idea that the lowland anoa and the mountain anoa are different species. An unexpectedly large genetic distance between the river and the swamp type of domestic buffaloes suggests a divergence time of about 1.7 Myr, while the swamp type was noticed to have the closest relationship with the tamaraw (1.5 Myr). This result implies that the two types of domestic buffaloes have differentiated at the full species level.
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  • 57
    ISSN: 1573-5028
    Keywords: cDNA ; evolution ; p2 protein ; ribosome ; Zea mays
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The nucleotide sequence of a full-length ribosomal P2 protein cDNA from maize was determined and used for a sequence comparison with the P2 and P1 proteins from other organisms. The integration of these data into a phylogenetic tree shows that the P proteins separated into the subspecies P1 and P2 before the eukaryotic kingdoms including plants developed from their ancestor.
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  • 58
    ISSN: 1573-5028
    Keywords: RNA editing ; tRNA editing ; chloroplast ; mitochondrion ; post-transcriptional modification ; initiation codon ; stop codon ; deamination ; evolution ; guide RNA ; transgenic plants ; plastid transformation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In the mitochondria and chloroplasts of higher plants there is an RNA editing activity responsible for specific C-to-U conversions and for a few U-to-C conversions leading to RNA sequences different from the corresponding DNA sequences. RNA editing is a post-transcriptional process which essentially affects the transcripts of protein coding genes, but has also been found to modify non-coding transcribed regions, structural RNAs and intron sequences. RNA editing is essential for correct gene expression: proteins translated from edited transcripts are different from the ones deduced from the genes sequences and usually present higher similarity to the corresponding non-plant homologues. Initiation and stop codons can also be created by RNA editing. RNA editing has also been shown to be required for the stabilization of the secondary structure of introns and tRNAs. The biochemistry of RNA editing in plant organelles is still largely unknown. In mitochondria, recent experiments indicate that RNA editing may be a deamination process. A plastid transformation technique showed to be a powerful tool for the study of RNA editing. The biochemistry as well as the evolutionary features of RNA editing in both organelles are compared in order to identify common as well as organelle-specific components.
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  • 59
    ISSN: 1573-5028
    Keywords: Calvin cycle ; sedoheptulose-1,7-bisphosphatase ; isoenzymes ; endosymbiosis ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Full-size cDNAs encoding the precursors of chloroplast fructose-1,6-bisphosphatase (FBP), sedoheptulose-1,7-bisphosphatase (SBP), and the small subunit of Rubisco (RbcS) from spinach were cloned. These cDNAs complete the set of homologous probes for all nuclear-encoded enzymes of the Calvin cycle from spinach (Spinacia oleracea L.). FBP enzymes not only of higher plants but also of non-photosynthetic eukaryotes are found to be unexpectedly similar to eubacterial homologues, suggesting a eubacterial origin of these eukaryotic nuclear genes. Chloroplast and cytosolic FBP isoenzymes of higher plants arose through a gene duplication event which occurred early in eukaryotic evolution. Both FBP and SBP of higher plant chloroplasts have acquired substrate specificity, i.e. have undergone functional specialization since their divergence from bifunctional FBP/SBP enzymes of free-living eubacteria.
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  • 60
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    Plant molecular biology 32 (1996), S. 685-692 
    ISSN: 1573-5028
    Keywords: evolution ; protein transport ; sec apparatus ; secA ; secY ; thylakoid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Plastids possess a bacteria-like sec apparatus that is involved in protein import into the thylakoid lumen. We have analyzed one of the genes essential for this process, secY. A secY gene from the unicellular red alga Cyanidium caldarium was found to be transcriptionally active, demonstrating for the first time that secY is functional in a plastid. Unlike the situation seen in bacteria the C. caldarium gene is transcribed monocistronically, despite the fact that it is part of a large ribosomal gene cluster that resembles bacterial spc operons. A molecular phylogeny is presented for 8 plastid-encoded secY genes, four of which have not been published yet. In this analysis plastid secY genes fall into two classes. One of these, comprising of genes from multicellular red algae and Cryptophyta, clusters in a neighbour-joining tree with a cyanobacterial counterpart. Separated from the aforesaid are secY genes from Chromophyta, Glaucocystophyta and a unicellular red alga. All plastid and cyanobacterial sequences are located on the same branch, separated from bacterial homologues. We postulate that the two classes of secY genes are paralogous, i.e. their gene products are involved in different protein translocation processes. Based on this assumption a model for the evolution of the plastid sec apparatus is presented.
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  • 61
    ISSN: 1573-4927
    Keywords: genome mapping ; evolution ; homology ; polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract We are developing a genetic map of the dog based partly upon markers contained within known genes. In order to facilitate the development of these markers, we have used polymerase chain reaction (PCR) primers designed to conserved regions of genes that have been sequenced in at least two species. We have refined the method for designing primers to maximize the number that produce successful amplifications across as many mammalian species as possible. We report the development of primer sets for 11 loci in detail:CFTR, COL10A1, CSFIR, CYP1A1, DCN1, FES, GHR, GLB1, PKLR, PVALB, andRB1. We also report an additional 75 primer sets in the appendices. The PCR products were sequenced to show that the primers amplify the expected canine genes. These primer sets thus define a class of gene-specific sequence-tagged sites (STSs). There are a number of uses for these STSs, including the rapid development of various linkage tools and the rapid testing of genomic and cDNA libraries for the presence of their corresponding genes. Six of the eleven gene targets reported in detail have been proposed to serve as “anchored reference loci” for the development of mammalian genetic maps [O'Brien, S. J.,et al., Nat. Genet. 3:103, 1993]. The primer sets should cover a significant portion of the canine genome for the development of a linkage map. In order to determine how useful these primer sets would be for the other genome projects, we tested the 11 primer sets on the DNA from species representing five mammalian orders. Eighty-four percent of the gene-species combinations amplified successfully. We have named these primer sets “universal mammalian sequence-tagged sites” because they should be useful for many mammalian genome projects.
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  • 62
    ISSN: 1573-4927
    Keywords: genome mapping ; evolution ; homology ; polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract We are developing a genetic map of the dog based partly upon markers contained within known genes. In order to facilitate the development of these markers, we have used polymerase chain reaction (PCR) primers designed to conserved regions of genes that have been sequenced in at least two species. We have refined the method for designing primers to maximize the number that produce successful amplifications across as many mammalian species as possible. We report the development of primer sets for 11 loci in detail:CFTR, COL10A1, CSFIR, CYP1A1, DCN1, FES, GHR, GLB1, PKLR, PVALB, andRB1. We also report an additional 75 primer sets in the appendices. The PCR products were sequenced to show that the primers amplify the expected canine genes. These primer sets thus define a class of gene-specific sequence-tagged sites (STSs). There are a number of uses for these STSs, including the rapid development of various linkage tools and the rapid testing of genomic and cDNA libraries for the presence of their corresponding genes. Six of the eleven gene targets reported in detail have been proposed to serve as “anchored reference loci” for the development of mammalian genetic maps [O'Brien, S. J.,et al., Nat. Genet. 3:103, 1993]. The primer sets should cover a significant portion of the canine genome for the development of a linkage map. In order to determine how useful these primer sets would be for the other genome projects, we tested the 11 primer sets on the DNA from species representing five mammalian orders. Eighty-four percent of the gene-species combinations amplified successfully. We have named these primer sets “universal mammalian sequence-tagged sites” because they should be useful for many mammalian genome projects.
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  • 63
    ISSN: 1573-5028
    Keywords: developmental regulation ; elongation factor ; evolution ; gene expression ; rhodophyte, sporophyte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The life cycle of the red alga Porphyra purpurea alternates between two morphologically distinct phases: a shell-boring, filamentous sporophyte and a free-living, foliose gametophyte. From a subtracted cDNA library enriched for sporophyte-specific sequences, we isolated a cDNA encoding an unusual elongation factor 1α (EF-1α) that is expressed only in the sporophyte. A second EF-1α gene that is expressed equally in the sporophyte and the gametophyte was isolated from a genomic library. These are the only EF-1α genes detectable in P. purpurea. The constitutively expressed gene encodes and EF-1α very similar to those of most eukaryotes. However, the sporophyte-specific EF-1α is one of the most divergent yet described, with nine insertions or deletions ranging in size from 1 to 26 amino acids. This is the first report of a developmental stage-specific EF-1α outside of the animal kingdom and suggests a fundamental role for EF-1α in the developmental process.
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  • 64
    ISSN: 1573-5028
    Keywords: carboxysomes ; evolution ; ribulose 1,5-bisphosphate carboxylase/oxygenase ; Synechococcus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Marine phycoerythrin-containing cyanobacteria are major contributors to the overall productivity of the oceans. The present study indicates that the structural genes of the carbon assimilatory system are unusually arranged and possess a unique primary structure compared to previously studied cyanobacteria. Southern blot analyses of Synechococcus sp. strain WH7803 chromosomal DNA digests, using the ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) large subunit gene from Synechococcus sp. strain PCC6301 as a heterologous probe, revealed the presence of a 6.4 kb HindIII fragment that was detectable at only low stringency. Three complete open reading frames (ORFs) were detected within this fragment. Two of these ORFs potentially encode the Synechococcus sp. strain WH7803 rbcL and rbcS genes. The third ORF, situated immediately upstream from rbcL, potentially encodes a homologue of the ccmK gene from Synechococcus sp. strain PCC7942. The deduced amino acid sequences of each of these ORFs are more similar to homologues among the β/γ purple bacteria than to existing cyanobacterial homologues and phylogenetic analysis of the Rubisco large and small subunit sequences confirmed an unexpected relationship to sequences from among the β/γ purple bacteria. This is the first instance in which the possibility has been considered that an operon encoding three genes involved in carbon fixation may have been laterally transferred from a purple bacterium. Analysis of mRNA extracted from cells grown under diel conditions indicated that rbcL, rbcS and ccmK were regulated at the transcriptional level; specifically rubisco transcripts were highest during the midday period, decreased at later times during the light period and eventually reached a level where they were all but undetectable during the dark period. Primer extension analysis indicated that the ccmK, rbcL and rbcS genes were co-transcribed.
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  • 65
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    Plant molecular biology 32 (1996), S. 923-936 
    ISSN: 1573-5028
    Keywords: PEPC ; C3 metabolism ; gene expression ; evolution ; gymnosperm ; Picea abies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Phosphoenolpyruvate carboxylase (PEPC) genes and cDNA sequences have so far been isolated from a broad range of angiosperm but not from gymnosperm species. We constructed a cDNA library from seedlings of Norway spruce (Picea abies) and identified cDNAs coding for PEPC. A full-length PEPC cDNA was sequenced. It consists of 3522 nucleotides and has an open reading frame (ORF) that encodes a polypeptide (963 amino acids) with a molecular mass of 109 551. The deduced amino acid sequence revealed a higher similarity to the C3-form PEPC of angiosperm species (86–88%) than to the CAM and C4 forms (76–84%). The putative motif (Lys/Arg-X-X-Ser) for serine kinase, which is conserved in all angiosperm PEPCs analysed so far, is also present in this gymnosperm sequence. Southern blot analysis of spruce genomic DNA under low-stringency conditions using the PEPC cDNA as a hybridization probe showed a complex hybridization pattern, indicating the presence of additional PEPC-related sequences in the genome of the spruce. In contrast, the probe hybridized to only a few bands under high-stringency conditions. Whereas this PEPC gene is highly expressed in roots of seedlings, a low-level expression can be detected in cotyledons and adult needles. A molecular phyiogeny of plant PEPC including the spruce PEPC sequence revealed that the spruce PEPC sequence is clustered with monocot and dicot C3-form PEPCs including the only dicot C4 form characterized so far.
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  • 66
    ISSN: 1432-2307
    Keywords: Apoptosis ; TUNEL ; Human gastric mucosa ; Carcinoma ; Ki-67
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the existence and distribution of apoptotic cells in human gastric mucosa, chronic gastritis, adenomatous dysplasias and carcinomas in 15 surgically removed stomachs in which dysplasia and carcinoma were found simultaneously. Serial sections were cut for immunohistochemistry for p53 oncoprotein and Ki-67 antigen, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labelling (TUNEL). TUNEL signal-positive apoptotic cells were rare in normal mucosa, while a few apoptotic cells were noted in gastritic mucosa and intestinal metaplasia, intermingled with Ki-67 antigen-positive cells forming a generative cell zone. This suggests the cell-cycle-dependent apoptosis of gastric mucosa. The frequency of apoptotic cells per crypt was higher in incomplete than in complete metaplasia, implying greater underlying DNA damage in the former. TUNEL indices (TI; percentage of TUNEL-positive cells in tumour cells) were slightly higher in adenomatous dysplasias (4.9±2.1) than in carcinoma (3.9±1.1), but there was no no statistical difference. Ki-67 indices (KI; percentage of Ki-67 antigen-positive cells in tumour cells) were significantly (P〈0.05) higher in carcinomas than in dysplasias. Thus, gastric adenomatous dysplasias were characterized by relatively higher TI and lower KI, which might reflect a more static growth potential. The expression of p53 oncoprotein in cancer cells is thought to be an apoptosis-suppressing event, although its precise role remains to be elucidated. Overall, these results indicate that apoptosis plays a crucial part in the morphogenesis of gastritic mucosa including intestinal metaplasia, and that the process is correlated both with tumourigenesis and with proliferative activity.
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  • 67
    ISSN: 1432-0878
    Keywords: Key words: Parkinson’s disease ; Dopamine neurons ; Transfection ; Conditioned medium ; GDNF ; BDNF ; Apoptosis ; Bonnet monkey ; Macaca radiata ; Rat (Sprague Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Fibroblasts derived from the cerebral cortex of an aged Bonnet monkey (Macaca radiata) were utilized to express recombinant cDNAs encoding rat glial-cell-line-derived neurotrophic factor (GDNF) and human prepro brain-derived neurotrophic factor (BDNF) by lipofection. The cells showed stable expression and secretion of biologically active proteins. Conditioned medium from fibroblasts expressing BDNF or GDNF increased the number of surviving mesencephalic tyrosine-hydroxylase-immunoreactive neurons after 7 days in culture. The trophic effects of BDNF and GDNF were examined at two different plating densities of embryonic mesencephalic cells. At 50 000 cells/cm2 plating density, treatment of the mesencephalic cultures with BDNF-conditioned medium increased the number of tyrosine-hydroxylase-immunoreactive neurons by about 40% compared with vector-transfected control. At the same plating density, GDNF-conditioned medium increased the number of surviving tyrosine-hydroxylase-immunoreactive neurons above the vector-transfected control by 30%. When the tissue was plated at a higher density, viz., 75 000 cells/cm2, the number of tyrosine-hydroxylase-immunoreactive neurons increased by 41% with BDNF-conditioned medium, and by 56% with GDNF-conditioned medium above vector-transfected controls. Conditioned medium from cells secreting GDNF was also found to reduce the number of apoptotic tyrosine-hydroxylase-immunoreactive cells by 50%.
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  • 68
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    Cell & tissue research 286 (1996), S. 55-62 
    ISSN: 1432-0878
    Keywords: Key words: Taste bud ; Denervation ; Apoptosis ; Cell death ; TUNEL method ; Glossopharyngeal nerve ; Circumvallate papilla ; Mouse (dd)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Apoptotic cells in the taste buds of mouse circumvallate papillae after the sectioning of bilateral glossopharyngeal nerves were examined by the method of DNA nick-end labeling (TUNEL), together with standard electron microscopy. The taste buds decreased in number and size 3–11 days after denervation and disappeared at 11 days. The TUNEL method revealed only a few positively stained nuclei in normal taste buds but, in those of mice 1–5 days after denervation, the number of positive nuclei had increased to 3–5 times that of taste buds from normal mice. Electron-microscopic observation after denervation demonstrated taste bud cells containing condensed and fragmentary nuclei in a cytoplasm with increased density. The results show that taste bud cells under normal conditions die by apoptosis at the end of their life span, and that gustatory nerve sectioning causes apoptosis of taste bud cells with taste buds decreasing in number and ultimately disappearing.
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  • 69
    ISSN: 1432-0878
    Keywords: Key words: Retinoids ; Vaginal epithelium ; Differentiation ; Keratin ; Apoptosis ; Estradiol ; Progesterone ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. In rodents, the vaginal epithelium shows cyclic changes with an alternating pattern of keratinization under estrogen control and mucification under progesterone control. Retinoids are powerful regulators of cell differentiation, an excess of retinoids suppressing the keratinizing differentiation of keratinocytes. Here, we have examined the vaginal epithelium during the estrous cycle and compare the effects of retinoids on both types of hormonally induced differentiation, i.e. keratinization and mucification. All-trans retinoic acid was administred either by daily injections during the estrous cycle or by a single injection before the estrogen rise; these two protocols gave similar results. Retinoic acid suppressed estrogen-induced vaginal keratinization and cytokeratin K10 expression (a biochemical marker of terminal differentiation). Progesterone-induced mucification was not impaired; however, retinoic acid impeded mucous cell desquamation, suggesting an effect of retinoic acid on cell adhesiveness. Retinoic acid induced the appearance of apoptotic-like cells, as revealed by immunocytochemical staining of DNA fragmentation.
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  • 70
    ISSN: 1432-0878
    Keywords: Key words: Thymus ; Thymic epithelial cells ; Cell culture ; Organ culture ; Apoptosis ; Mouse (C57BL/6J)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Apoptosis of murine thymocytes was examined either in intact fetal thymus lobes or in thymus cell suspensions, both cultured alone or in the presence of either a cortical (TEC 1.4) or a medullary (TEC 2.3) thymic epithelial cell line. Both TECs induced a pronounced increase of apoptosis in 24-h cultivated single thymus cell suspensions but not in spleen or bone marrow cell cultures. Co-culture of thymocytes with murine fibroblasts did not enhance apoptosis of the thymus cells. A similar enhancement of thymocyte apoptosis was observed with dialysed culture supernatants derived from both TEC lines, the active component(s) having a molecular weight of 〉30 kDa. In contrast, the cortical TEC 1.4 had a pronounced apoptosis inducing effect on intact fetal thymus lobes cultivated for six days, whereas the medullary TEC 2.3 had only a marginal influence. TEC 1.4 also induced a significant alteration in the ratio of CD4+CD8+ to CD4-CD8- cells. It is concluded that both the cortical and medullary epithelial cell lines are able to induce thymocyte apoptosis but that a large proportion of the cells within the intact thymus stroma is refractory to the respective signal(s) of the medullary epithelial cell line.
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  • 71
    ISSN: 1432-0878
    Keywords: Key words: Adrenal cortex ; Apoptosis ; DNA fragmentation ; DNA 3′-end labeling ; Adrenocorticotropic hormone ; Hypophysectomy ; Rat (Sprague Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Adrenocortical cell apoptosis was studied by using an established in vivo model, the hypophysectomized rat, and an in vitro model, viz., rat adrenal glands in short-term organ culture. In vivo, apoptosis (biochemical autoradiographic analysis of internucleosomal DNA cleavage) was weak and not apparent until 12–24 h after hypophysectomy. In situ histochemical localization of 3′-end DNA strand breaks revealed that apoptosis in vivo occurred nearly exclusively in subpopulations of zona reticularis cells. Adrenocorticotropic hormone (ACTH) maintenance completely blocked these indices of apoptosis. By contrast, apoptosis (DNA fragmentation) in cultured rat adrenal glands without ACTH was extensive and relatively rapid, being apparent after 1 h and increasing with the duration of incubation. ACTH attenuated (by 44%) but did not completely block apoptosis in vitro. Thus, ACTH appears to be the sole pituitary hormone that forestalls apoptosis of terminally differentiated adrenocortical (zona reticularis) cells. However, the discrepancy between in vitro and in vivo models in terms of the magnitude and rate of DNA fragmentation suggests that, in vivo, other factors finely regulate the magnitude of adrenocortical apoptotic cell death.
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  • 72
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    Plant systematics and evolution 201 (1996), S. 149-162 
    ISSN: 1615-6110
    Keywords: Colchicaceae ; Androcymbium ; Allozymes ; morphology ; endemism ; evolution ; conservation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Narrow endemism is a poor predictor of genetic potential in the six taxa that conform theAndrocymbium gramineum complex, as shown by the unexpectedly high values of variability associated with ten allozymic loci and 13 biometrical variables. Although both levels are shown not to be correlated, variability is always concentrated within populations. This result, together with environmental, reproductive and historical data strongly suggests differentiation in local isolates, where changes can be quickly assimilated by stochastic processes. A key implication for conservation is that sampling within the largest population will save effort while neglecting only very low frequency alleles.
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  • 73
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    Plant systematics and evolution 200 (1996), S. 1-11 
    ISSN: 1615-6110
    Keywords: Juncaceae ; Luzula sect.Luzula ; Taxonomy ; karyotypes ; evolution ; Flora of Spain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A survey ofLuzula sect.Luzula (Juncaceae) with data on karyology, morphology and distribution in the Iberian Peninsula is provided. Names published from the region are evaluated.L. campestris subsp.campestris, L. c. subsp.nevadensis, L. sudetica, L. ×heddae, L. congesta, L. ×danica, L. alpina, L. multiflora, andL. multiflora s. l. are discussed. A diploid taxon with agmatoploid karyotype, morphologically close toL. multiflora andL. alpina, has been revealed and is described asL. multiflora subsp.monticola. L. campestris subsp.iberica has been relegated to the synonymy of subsp.campestris, L. c. subsp.carpetana was found to belong toL. multiflora s. l.
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  • 74
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    Plant systematics and evolution 199 (1996), S. 17-32 
    ISSN: 1615-6110
    Keywords: Apiaceae ; Umbelliferae ; Anthriscus ; Taxonomy ; phylogeny ; evolution ; ecological radiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Species boundaries and phylogenetic relationships of 17 taxa ofAnthriscus (Apiaceae), with special emphasis on the critical sect.Cacosciadium, were explored using morphological data with principal component analysis, phenetics, and phylogenetics. The analyses did not provide satisfactory resolution of taxa from sect.Cacosciadium and only four species were retained. The total number of species was reduced to nine. Sect.Cacosciadium is distinguished by only two synapomorphies while sects.Anthriscus andCaroides are better supported. Present geographic and ecological variation suggests that the radiation ofAnthriscus occurred through divergence of peripheral isolated populations adapting to different habitats: high montane meadows and screes, shady climax forests, and seasonally dry habitats at lower altitudes. The adaptive significance of particular morphological traits is discussed.
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  • 75
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    Plant systematics and evolution 202 (1996), S. 121-135 
    ISSN: 1615-6110
    Keywords: Rubiaceae ; Galium ; Allozyme variation ; systematics ; ploidy level ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Allozyme variation at 11 loci (with 37 alleles) was studied electrophoretically in seven outbreeding, closely related diploid and tetraploid taxa, seven from sect.Leptogalium and two from sect.Leiogalium. Whereas the sections are clearly distinct by several different alleles, aggregates, species and subspecies differ only in the frequency or presence/absence of common alleles. The resulting dendrogram suggests phylogenetic relationships and is supported by other multidisciplinary evidence. Tetraploids have originated independently in several groups, and there is evidence for tetrasomic inheritance and thus for autopolyploidy in spite of normal meiotic bivalent pairing and partly suspected hybrid origin. Tetraploids differ from related diploids only little in number of alleles and expected heterozygosity within populations, but clearly exhibit higher numbers of genotypes. This often corresponds to their greater morphological variability, increased adaptive flexibility, and better colonizing capacity compared to related diploids.
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  • 76
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    Plant systematics and evolution 203 (1996), S. 111-142 
    ISSN: 1615-6110
    Keywords: Pelargonium ; sect.Hoarea ; Chromosomes ; B chromosomes ; Robertsonian translocation ; centric fusion ; evolution ; systematics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Chromosome numbers of 65 species of sect.Hoarea have been determined. These show three basic chromosome numbers, x = 11, 10 and 9. Only a few species are tetraploid. In five species both diploid and tetraploid cytotypes are reported. Several cases of deviations in chromosome numbers and cytological abnormalities were found, most of these being related to the presence of B chromosomes that occur in eight species. Evidence is presented to suggest that the basic chromosome numbers of x = 10 and x = 9 are derived from x = 11 by centric fusion. Although variation in basic chromosome number withinPelargonium has been the subject of detailed study, this is the first time that evidence has been found for a mechanism of change in basic number, that of centric fusion by Robertsonian translocation. For the species of sect.Hoarea with x = 9, where the evidence for Robertsonian translocation is greatest, this process has probably taken place quite recently. In contrast to results from other sections of the genusPelargonium, the three different basic numbers of sect.Hoarea do not contradict its delimitation as a natural taxon.
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  • 77
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    Biology and philosophy 11 (1996), S. 21-31 
    ISSN: 1572-8404
    Keywords: Morality ; evolution ; justification ; objectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Philosophy
    Notes: Abstract A familiar position regarding the evolution of ethics is that biology can explain the origin of morals but that in doing so it removes the possibility of their having objective justification. This position is set fourth in detail in the writings of Michael Ruse (1986, 1987, 1989, 1990a, 1990b) but it is also taken by many others, notably, Jeffrie Murphy (1982), Andrew Oldenquist (1990), and Allan Gibbard (1990), I argue the contrary view that biology provides a justification of the existence of morals which is objective in the sense of being independent of people's moral views and their particular desires and preferences. Ironically, my argument builds on the very premises which are supposed to undermine the objectivity of morals. But my argument stops short of claiming that biology can give us a basis for justifying some particular system of morals. Drawing on an analogy with social contract theory, I offer a general reason why this more ambitious project cannot be expected to succeed if the argument is pursued along the same lines. Finally, I give reasons why the possibility of objective justification for a particular morality cannot be ruled out in general on evolutionary grounds.
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    Biology and philosophy 11 (1996), S. 33-65 
    ISSN: 1572-8404
    Keywords: Background assumptions ; Darwinism ; evolution ; Newtonian dynamics ; nonequilibrium thermodynamics ; nonlinear dynamics ; probability revolution ; selection ; self-organization ; systems dynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Philosophy
    Notes: Abstract The Darwinian concept of natural selection was conceived within a set of Newtonian background assumptions about systems dynamics. Mendelian genetics at first did not sit well with the gradualist assumptions of the Darwinian theory. Eventually, however, Mendelism and Darwinism were fused by reformulating natural selection in statistical terms. This reflected a shift to a more probabilistic set of background assumptions based upon Boltzmannian systems dynamics. Recent developments in molecular genetics and paleontology have put pressure on Darwinism once again. Current work on self-organizing systems may provide a stimulus not only for increased problem solving within the Darwinian tradition, especially with respect to origins of life, developmental genetics, phylogenetic pattern, and energy-flow ecology, but for deeper understanding of the very phenomenon of natural selection itself. Since self-organizational phenomena depend deeply on stochastic processes, self-organizational systems dynamics advance the probability revolution. In our view, natural selection is an emergent phenomenon of physical and chemical selection. These developments suggest that natural selection may be grounded in physical law more deeply than is allowed by advocates of the autonomy of biology, while still making it possible to deny, with autonomists, that evolutionary explanations can be modeled in terms of a deductive relationship between laws and cases. We explore the relationship between, chance, self-organization, and selection as sources of order in biological systems in order to make these points.
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    Biology and philosophy 11 (1996), S. 193-214 
    ISSN: 1572-8404
    Keywords: Adaptationism ; avatars ; competition ; explanation ; evolution ; macroevolution ; optimality ; reductionism ; species selection ; species sorting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Philosophy
    Notes: Abstract The ontological dependence of one domain on another is compatible with the explanatory autonomy of the less basic domain. That autonomy results from the fact that the relationship between two domains can be very complex. In this paper I distinguish two different types of complexity, two ways the relationship between domains can fail to be transparent, both of which are relevant to evolutionary biology. Sometimes high level explanations preserve a certain type of causal or counterfactual information which would be lost at the lower level; I argue that this is central to the proper understanding of the adaptationist program. Sometimes high level kinds are multiply realised by lower level kinds: I argue that this is central to the understanding of macroevolution.
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  • 80
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    Biology and philosophy 11 (1996), S. 215-244 
    ISSN: 1572-8404
    Keywords: Classes ; classification ; evolution ; Buffon ; Darwin ; Ghiselin ; individuality ; ordering ; concept of species
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Philosophy
    Notes: Abstract Since the 1970s, there has been a tremendous amount of literature on Ghiselin's proposal that “species are individuals”. After recalling the origins and stakes of this thesis in contemporary evolutionary theory, I show that it can also be found in the writings of the French naturalist Buffon in the 18th Century. Although Buffon did not have the conception that one species could be derived from another, there is an interesting similarity between the modern argument and that of Buffon regarding the “individuality of species’. The analogy is strong enough to force us to recognize that genuine evolutionary (or Darwinian) questions might be of secondary importance in the discussion. In consequence, the third section of the paper proposes an alternative schema for the “logical structure” of the Darwinian concept of species. Darwin distinguished the problem of the designation of a concrete species, and the problem of its signification of species within his theory of descent? The resulting notion of species involves a logical structure based on the fusion of the logical operations of classification and ordering. The difficulty — and interest — is that this interpretation of species does not entail any precise operational definition of species; it can only tell us what the ultimate signification of classification is within the theory of descent with modification through natural selection.
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  • 81
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    Biology and philosophy 11 (1996), S. 377-403 
    ISSN: 1572-8404
    Keywords: development ; developmental systems ; gene ; genetic information ; evolution ; information ; inheritance ; interactor ; Lamarck ; Meme ; replicator ; selection ; unit of selection ; vehicle ; Weismann
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Philosophy
    Notes: Abstract This paper evaluates and criticises the developmental systems conception of evolution and develops instead an extension of the “gene's eye” conception of evolution. We argue (i) Dawkin's attempt to segregate developmental and evolutionary issues about genes is unsatisfactory. On plausible views of development it is arbitrary to single out genes as the units of selection. (ii) The genotype does not carry information about the phenotype in any way that distinguishes the role of the genes in development from that other factors. (iii) There is no simple and general causal criterion which distinguishes the role of genes in development and evolution. (iv) There is, however, an important sense in which genes but not every other developmental factor represent the phenotype. (v) The idea that genes represent features of the phenotype forces us to recognise that genes are not the only, or almost the only, replicators. Many mechanisms of replication are involved in both development and evolution. (vi) A conception of evolutionary history which recognises both genetic and non-genetic replicators, lineages of replicators and interactors has advantages over both the radical rejection of the replicator/interactor distinction and the conservative restriction of replication to genetic replication.
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    Biology and philosophy 11 (1996), S. 405-420 
    ISSN: 1572-8404
    Keywords: species ; evolution ; natural selection ; gradualism ; punctuated equilibria ; variation ; Lamarck ; Darwin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Philosophy
    Notes: Abstract Species are thought by many to be important units of evolution. In this paper, I argue against that view. My argument is based on an examination of the role of species in the synthetic theory of evolution. I argue that if one adopts a gradualist view of evolution, one cannot make sense of the claim that species are “units” in the minimal sense needed to claim that they are units of evolution, namely, that they exist as discrete entities over time. My second argument is directed against an appeal to Eldredge and Gould's theory of punctuated equilibria to support the claim that species are units of evolution. If one adopts their view, it may be possible to identify discrete temporal entities that can plausibly be termed ‘species’, but there is no reason to claim that those entities are “units of evolution”. Thus, on two plausible interpretations of the role of natural selection in the process of evolution, species are of no special importance. I then consider some of the reasons why species have been thought to be important evolutionary units by many contemporary evolutionary biologists. Finally, I discuss briefly the implications of this conclusion for evolutionary biology.
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    Biology and philosophy 11 (1996), S. 543-559 
    ISSN: 1572-8404
    Keywords: Creationism ; evidence ; evolution ; naturalism ; Phillip Johnson ; scientific methodology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Philosophy
    Notes: Abstract Phillip Johnson claims that Creationism is a better explanation of the existence and characteristics of biological species than is evolutionary theory. He argues that the only reason biologists do not recognize that Creationist's negative arguments against Darwinism have proven this is that they are wedded to a biased ideological philosophy —Naturalism — which dogmatically denies the possibility of an intervening creative god. However, Johnson fails to distinguish Ontological Naturalism from Methodological Naturalism. Science makes use of the latter and I show how it is not dogmatic but follows from sound requirements for empirical evidential testing. Furthermore, Johnson has no serious alternative type of positive evidence to offer for Creationism, and purely negative argumentation, despite his attempt to legitimate it, will not suffice.
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    Biology and philosophy 12 (1996), S. 51-71 
    ISSN: 1572-8404
    Keywords: philosophy of mind ; ethics ; animal pain ; Peter Carruthers ; consciousness ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Philosophy
    Notes: Abstract In a series of works, Peter Carruthers has argued for the denial of the title proposition. Here, I defend that proposition by offering direct support drawn from relevant sciences and by undercutting Carruthers‘ argument. In doing the latter, I distinguish an intrinsic theory of consciousness from Carruthers‘ relational theory of consciousness. This relational theory has two readings, one of which makes essential appeal to evolutionary theory. I argue that neither reading offers a successful view.
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  • 85
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    Journal of science education and technology 5 (1996), S. 193-201 
    ISSN: 1573-1839
    Keywords: Chemistry ; chemistry education ; multiple intelligences ; imagery ; visual-spatial thinking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Natural Sciences in General , Technology
    Notes: Abstract Chemistry has evolved from a science dominated by mathematics into a science highly dependent on spatial-visual intelligence. Yet the chemical content of introductory courses remains taught essentially the same as 40–50 years ago. Chemistry, today, is recognized by chemists as the molecular science. Yet, school chemistry is alienated from that perception. Thanks to the computer, young people are more comfortable with visual imaging than their instructors were at the same age. Thus the time is rife to reinvigorate chemistry education by means of the visual-spatial approach, an approach wholly in conformance with the way modern chemistry is thought about and practiced.
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  • 86
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    Quality & quantity 30 (1996), S. 161-171 
    ISSN: 1573-7845
    Keywords: entropy ; transportation ; evolution ; structure of system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Sociology
    Notes: Abstract The need for a concept of economic entropy is discussed and a definition of economic entropy is given. The system of transportation is described in terms of economic entropy. The structure of energy resources is examined and used in analysis of the economic development of various countries and of the characteristic features of economic entropy.
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  • 87
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    Hydrobiologia 325 (1996), S. 1-30 
    ISSN: 1573-5117
    Keywords: subterranean Cladocera ; history ; ecology ; adaptation ; evolution ; biogeography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A synthesis of current knowledge of the Cladocera living in non-surface waters is provided. For all 94 species and subspecies recorded (Dec. 1994) we give information on their ranges, ecological characteristics, and a review of literature data. We also give a historic survey of the development of concepts, identify categories among groundwater-dwelling species, and discuss their adaptations and the evolutionary lines present. Of the estimated total of c. 450 non-marine Cladocera of the world, c. 20% may occur in underground aquatic habitats, but true groundwater forms (stygobionts or stygobites) are relatively few, possibly not more than 10 species (c. 2.5% of the total). This number may increase, as attention is given to subterranean habitats outside Europe.
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  • 88
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    Hydrobiologia 320 (1996), S. 15-26 
    ISSN: 1573-5117
    Keywords: Crustacea ; diapause ; photoperiod responses ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Definitions of diapause and of the three types of diapause (embryonal, larval and imaginal) as they apply to the Crustacea are given and the distribution of the types among different orders of crustaceans is discussed. A special role of diapause as a way to escape competition among ecologically similar species is noted and the significance of photoperiod responses as a pace-maker of the biorhythmical function of diapause for a wide range of species is demonstrated. A common unspecific regression for the description of oxygen consumption with duration of diapause in crustaceans of different sizes, different orders and different types of diapause is suggested. A special significance of embryonal diapause for the adaptation of palaeo-, meso- and neolimnic species of crustaceans that migrated from the sea into inland waterbodies is postulated.
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  • 89
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    Hydrobiologia 334 (1996), S. 277-285 
    ISSN: 1573-5117
    Keywords: leech ; oligochaete ; parasite ; evolution ; phylogeny
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Powerful tests of adaptational hypotheses can be made in the context of well-supported cladograms by investigating the most parsimonious transformation of intrinsic or extrinsic factors to explain their distribution across taxa in a cladogram. Such tests are used here to discover patterns of life-history evolution in leeches; in particular in relation to exploitation of terrestrial and aquatic habitats, parental care and resource utilization. Moreover, the relationships among leeches, acanthobdellids and branchiobdellids is reaffirmed as is their collective placement within the oligochaetes.
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  • 90
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    Hydrobiologia 320 (1996), S. 1-14 
    ISSN: 1573-5117
    Keywords: diapause ; freshwater Crustacea ; antiquity ; diversity ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract After a brief historical review of the discovery of diapause in freshwater crustaceans, its dramatic nature in certain cyclopoid copepods, in which diapausing individuals may occur at densities of 〉 106 per m2, is used to illustrate the enormous ecological significance of the phenomenon. Some of the problems presented by dispause in cyclopoid copepods are noted, including the different behaviour in different lakes of what appears to be a single species. Different physiological cues or different genetic endowments are clearly involved. The wider incidence of diapause in freshwater copepods and ostracods is noted. Among freshwater crustaceans it it the Branchiopoda that have universally adopted diapause, always at the egg stage. Even such an ancient order as the Anostraca, perhaps the most primitive of all crustaceans, produces elaborately constructed resting eggs that are capable of cryptobiosis, can remain viable in a dry state for long periods, and can tolerate extreme conditions. The nature of branchiopod resting eggs is briefly reviewed. Of these, only those of the Anomopoda are protected by containers derived from the parental carapace. These are mechanically complex in the most advanced species but, as shown by fossils, are extremely ancient structures. Factors initiating the onset and termination of diapause in branchiopods are briefly noted, and the process of hatching of resting eggs is outlined.
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  • 91
    ISSN: 1573-5117
    Keywords: Larval development ; chthamalid barnacle ; Octomeris sulcata ; food preference ; evolution ; gnathobase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Embryos obtained from gravid adults of the chthamalid barnacle Octomeris sulcata Nilsson-Cantell from Japan and Korea were cultured through six naupliar stages to the cyprid and juvenile barnacle stage in laboratory conditions, fed either the diatom Skeletonema costatum (Grev.) Cleve or the dinoflagellate Prorocentrum minimum (Pavillard) Schiller. The nauplii were planktotrophic and, depending on diet, reached the cyprid stage 9 or 17 days after hatching in individual cultures at 22 °C with 24 h illumination. The survival rate was higher and the duration of the naupliar stages was shorter when fed P. minimum rather than S. costatum. This is probably due to the presence of feathered setae on the antennae. Feathered or plumose setae in nauplii of different cirripede taxa are apparently linked to the type of phytoplankton in the seas when these taxa first evolved. The larval stages of O. sulcata are described, and morphological differences between larvae reared from Japanese andKorean adults are compared. The polygonal cephalic shield and unilobed labrum, a pair of posterior shield spines after naupliar stage IV, feathered setae and a hispid seta on the coxa of the antenna, a cuspidate seta on the mandible, and the gnathobase of the antenna are important in distinguishing the nauplii of this species from other species, including Chthamalidae.
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  • 92
    ISSN: 1573-6849
    Keywords: chromosome ; evolution ; FISH ; intrachromosomal rearrangements ; phylogeny ; subregional chromosome painting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We have usedAlu polymerase chain reaction generated probes from rearranged human/rodent somatic cell hybrids for fluorescencein situ hybridization and comparative mapping of some intrachromosomal changes in the karyotypes of great apes (Pan troglodytes, P. paniscus, Gorilla gorilla Pongo pygmaeus), a gibbon (Hylobates lar), and an Old World monkey (Macaca fuscata). Probes containing chromosomes 2 and 18 fragments confirmed inversions already suggested by the banding pattern of great ape homologues. However, a chromosome 3 fragment showed complex rearrangements in the gibbon and macaque karyotype which were previously not well defined from banding. ‘Subchromosomal painting’ will allow the identification of intrachromosomal changes on the basis of DNA homology and provides a powerful method to study karyological and genomic evolution.
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  • 93
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    Apoptosis 1 (1996), S. 75-80 
    ISSN: 1573-675X
    Keywords: Apoptosis ; calpain ; protein kinase C ; serine protease inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The effects of a synthetic serine protease inhibitor, FOY-305, and its derivatives, ONO-3403 and FO-349, on the proliferation of mouse NIH3T3 cells were investigated. At concentrations between 10 and 100 μg/ml, three protease inhibitors induced a moderate suppression of cell growth. However, only ONO-3403 showed severe cytotoxicity at concentrations higher than 200 μg/ml. Results of TUNEL staining and DNA fragmentation analysis indicated that ONO-3403 induced apoptosis at the high concentrations. Biochemical analysis has shown that ONO-3403 directly enhanced the amidolytic activity of purified μ-calpain at a concentration higher than 100 μg/ml while FOY-305 and FO-349 showed less effects. When the cell extract was incubated in the presence of ONO-3403, specific degradation of a few proteins including protein kinase C was observed. Similar degradation was also observed by addition of μ-calpain to the extract. These results imply that ONO-3403 is a specific stimulator of calpain. It seems reasonable to conclude that increase in calpain activity results in apoptosis.
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  • 94
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    Apoptosis 1 (1996), S. 153-160 
    ISSN: 1573-675X
    Keywords: Apoptosis ; cyclobutane pyrimidine dimers ; photoreactivation ; poly(ADP-ribose) polymerase ; UV-damage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Rat kangaroo(Potorous tridactylus) cells efficiently repair 254 nm ultraviolet light (UV) induced cyclobutane pyrlmidine dimers (CPDs) through photoreactivation, leading to an enhancement of survival when cells are exposed to photoreactivation light (PRL) immediately after UV-irradiation. This work presents evidence that at least part of the UV-irradiated cells die through apoptosis, as demonstrated by DNA fragmentation and chromatin condensation. The induction of this kind of cell death can be reversed through photoreactivation immediately after irradiation, indicating that CPDs are essential signals for the initiation of apoptosis by UV-irradiation. Exposure to PRL 24 h after UV-irradiation does not reverse the induction of apoptosis, implying that the cells are committed to die at this time after irradiation. Inhibition of DNA synthesis during this period of time following UV-irradiation, and before exposure to PRL, does not avoid apoptosis. Since similar results were obtained in Go confluent and G1/S synchronized cells, the signals for the UV-induced apoptosis do not seem to be related to a specific phase of cell cycle. Nevertheless, by adding 3-aminobenzamide (3AB—an inhibitor of poly(ADP-ribose) polymerase) in the cell medium after UV-irradiation, apoptosis endpoints were partially reversed if cells are exposed to PRL 24 h later. This result strongly indicates that poly(ADP-ribose) is an intermediary signal for UV-induced apoptosis in mammalian cells.
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  • 95
    ISSN: 1573-675X
    Keywords: Apoptosis ; Bax ; Bcl-2 ; CDC 2 ; cyclin B1 ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Paclitaxel is a potential cancer chemotherapeutic agent for ovary, breast, and head and neck cancers; its effects on nasopharyngeal carcinoma (NPC) have not been reported previously. This study investigated the cytotoxic mechanism of paclitaxel in two NPC cell lines, NPC-TW01 and NPC-TW04. NPC cells treated with pacli-taxel showed convoluted nuclei, condensed chromatin and decreased cellular and nuclear volume, and also exhibited genomic DNA degradation into multiple oligonucleosomal fragments, suggesting that pacli-taxel induced apoptosis in these cells. The effects of paclitaxel on apoptosis-related proteins including Bcl-2, Bax and CDC 2 were also detected. Although the levels of Bcl-2 and Bax were not changed in NPC cells following treatment with 5 nM-1 μM of paclitaxel, phosphorylation of Bcl-2 was significantly observed in the cells treated with 1 μM of paclitaxel for 12 hours. In addition, cyclin B1-associated CDC 2 kinase was highly activated in the NPC cells exposed to paclitaxel even at low (5 nM) concentration, and this result is associated with the finding that low concentration of paclitaxel is able to induce apoptosis in NPC cells.
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  • 96
    ISSN: 1573-675X
    Keywords: Apoptosis ; bcr-abl ; cisplatin ; chronic myeloid ; leukaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Chronic myeloid leukaemia (CML) cell lines expressing the bcr-abl fusion gene are resistant to drug-induced apoptosis. Using a human CML cell line (EM2), we investigated the effects of cisplatinum (DDP), Doxorubicin and Tallimustine on the level of p210, the product of the hybrid bcr-abl gene, and on the induction of apoptosis. DDP exposure of this cell line resulted in a decrease of p210 levels with a concomitant activation of apoptosis. At all the concentrations tested, neither Doxorubicin nor Tallimustine were able to induce DNA fragmentation nor to reduce the levels of the fusion protein p210. The reduction in the p210 levels induced by DDP were also observed at mRNA level as observed with RT-PCR, suggesting that, at least in part, the decrease in p210 levels was the result of a reduction in the transcription of the bcr-abl fusion gene. The DDP-induced DNA fragmentation and decrease in p210 levels, were observed in EM2 cells but not in another human CML cell line (K562) which overexpresses the fusion gene. In K562 cells the levels of bcr-abl, although decreased, remained well detectable after DDP treatment. Data indicate that it may be possible to investigate compounds able to contrast the resistance to DNA-damage induced apoptosis of CML cell lines.
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  • 97
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    Apoptosis 1 (1996), S. 40-48 
    ISSN: 1573-675X
    Keywords: Apoptosis ; endonuclease ; intracellular pH ; ion channels ; review
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Programmed cell death is a stereotyped and highly conserved process leading to deletion of unwanted cells. The process may be initiated in response to physiologic signals (Fas ligation, removal of extra-cellular matrix or growth factors), or pathologic events (DNA damage, hypoxia/reperfusion injury, viral infection). Some of the signal transduction pathways between a specific stimulus and the commitment to apoptosis are being worked out, although these may not represent general pathways for all triggers of apoptosis. In addition, the cell is able to integrate a variety of signals, some favoring apoptosis and some favoring survival, and to make a life-or-death decision. This has been termed the ‘judgment phase’, whereas once the cell is irreversibly committed to apoptosis, the ‘execution phase’ is initiated. The biochemical features of the ‘execution phase’ are still unclear; DNA cleavage probably represents one of the final events of the execution phase, but what about the multitude of proteases that participate in the process, phosphatidylserine externalization, transglutaminase activation, and, of course, the subject of this discussion, cytoplasmic acidification? Where do these events fit into the process, and what are the relationships of one to the other? This review will address the following points: (1) Is cytoplasmic acidification a universal feature of apoptosis, and is it essential? The reported cases examined to date will be evaluated. (2) How is cytoplasmic acidification accomplished? Is acidification sufficient for apoptosis to occur? (3) What are the consequences of acidification, particularly with respect to other biochemical features of apoptosis? (4) Finally, I would like to advance the hypothesis that acidification may represent the cellular mechanism for integration of multiple signals; cytoplasmic acidification could represent the point of no return on the road to apoptosis.
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    Apoptosis 1 (1996), S. 147-152 
    ISSN: 1573-675X
    Keywords: Apoptosis ; DNA fragmentation ; DNase γ ; programmed cell death ; thymocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The physiological and pathological importance of cell death by apoptosis has recently been recognized. One of the hallmarks of apoptosis is the enzymatic cleavage of genomic DNA into nucleosomal oligomers. The identification of an endonuclease responsible for apoptosis might help to explain how this cell suicide is regulated and why DNA is cleaved. Here, we found that γ type of DNase was retained in apoptotic rat thymocyte nuclei. Homogeneously purified DNase γ (Mr = 33 kDa) from the apoptotic nuclei was revealed to be a Ca2+/Mg2+-dependent endonuclease and inhibited by Zn2+. This enzyme cleaved chromosomal DNA with 3′-hydroxyl (OH) and 5′-phosphoryl (P) ends. The cleavage ends and its divalent cation dependencies match those observed in apoptotic thymocytes induced by X-irradiation or glucocorticoid treatment, indicating that this endonuclease is a central component of the thymic apoptosis machinery.
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  • 99
    ISSN: 1573-675X
    Keywords: Apoptosis ; cell proliferation ; IL-2 ; Ras
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Oncoproteins of the Ras family have been extensively studied because of their implication in human cancer. Their roles have been primarily assigned to the commandment of cell proliferation and suppression of apoptosis, which has also been demonstrated by the involvement of Ras activation in the signal transduction pathways triggered by most cytokine receptors. Nevertheless, the functions of Ras proteins have been extended in the last years by the findings showing that they can also act as promoters or enhancers of apoptosis in various systems and conditions. These considerations have raised the issue as to how the signals delivered by Ras are regulated and translated in terms of cellular responses, suggesting that signal complementation may direct the final fate of cells. As an example, the interleukin-2 receptor system may represent a useful model in which the meaning of Ras signals may be evaluated in terms of interactions with other simultaneous signalling events, since knowledge of the biochemical events triggered by the interaction of interleukin-2 with its cell surface receptor in lymphocytes has allowed the proposal of a complete signalling model arranged in three independent channels, one of which is mediated by Ras.
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  • 100
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    Apoptosis 1 (1996), S. 33-39 
    ISSN: 1573-675X
    Keywords: Apoptosis ; Bcl-2 ; epidermal growth factor ; epidermal growth factor receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Apoptosis, or programmed cell death, plays an important role in the pathogenesis of a number of human diseases, including cancers, autoimmune diseases, and neurodegenerative disorders. Recent evidence suggests that EGF induced signal transduction pathways which govern cell proliferation and cell cycle progression also mediate antiproliferative effects leading to increased apoptosis in cells that express high levels of epidermal growth factor receptors. Treatments designed to increase apoptosis have potential to change the natural progression of cancer and eventually lead to its successful control.
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