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  • 1995-1999  (681)
  • 1880-1889  (694)
  • 1999  (681)
  • 1888  (694)
  • Inorganic Chemistry  (694)
  • Industrial Chemistry  (469)
  • apoptosis  (112)
  • Immunohistochemistry  (100)
  • Nuclear reactions
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  • 1995-1999  (681)
  • 1880-1889  (694)
Year
Keywords
  • 101
    Electronic Resource
    Electronic Resource
    The interaction of Bcl-2 and Bax regulates apoptosis in biliary epithelial cells of rats with obstructive jaundice (1999)
    Springer
    Virchows Archiv 434 (1999), S. 333-339 
    Details
    ISSN: 1432-2307
    Keywords: Key words Apoptosis ; Programmed cell death ; Ductular proliferation ; Biliary decompression ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A complex molecular network controls cell homeostasis by inducing apoptosis or proliferation. The balance of Bcl-2 and Bax, members of a protein family, determines whether a cell will become immortal (Bcl-2) or will undergo apoptosis (Bax). To determine the role of Bcl-2 and Bax during proliferation of biliary epithelial cells (BEC) after bile duct ligation (BDL) and their regression after biliary decompression we induced hyperplasia of BEC by BDL in male rats. Regression of hyperplastic BEC by way of apoptosis was induced by biliary decompression through a Roux-en-Y biliodigestive anastomosis. To quantify apoptosis a modified TUNEL assay was used. Expression of Bcl-2 and Bax was visualized by immunohistochemistry and quantified stereologically. BEC increased from 〈1% to 〉20% after BDL; this increase was associated with overexpression of Bcl-2 in up to 30% of hyperplastic BEC. After biliodigestive anastomosis, apoptotic BEC increased from 〈0.1% to a peak of 5.4% after 1 day to reach baseline again 1 week after decompression. This was associated with de novo appearance of Bax. The interaction between Bcl-2 and Bax triggers apoptosis in BEC and acts as a cell rheostat in BEC hyperplasia and its involution after biliary decompression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050349
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  • 102
    Electronic Resource
    Electronic Resource
    Intimal-type primary sarcoma of the aorta (1999)
    Springer
    Virchows Archiv 435 (1999), S. 62-66 
    Details
    ISSN: 1432-2307
    Keywords: Key words Rhabdomyosarcoma ; Aorta ; Immunohistochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report an intimal sarcoma presenting as an aortic aneurysm. A 68-year-old man suffered from chest pain and speech disturbance. Computed tomography showed a sacciform aneurysm of the aorta, which was resected, revealing a polypoid tumour measuring 1.5×2×2.5 cm projecting into the lumen. This proved to be a poorly differentiated high-grade sarcoma having morphological, immunophenotypic and ultrastructural features consistent with rhabdomyosarcomatous differentiation. Primary sarcomas of the aorta are extremely rare. Many cases have been diagnosed as ”intimal” on the basis of their site of origin, and they are not easy to classify from their histological pattern. Electron microscopy and the use of a more comprehensive panel of immunohistochemical markers should be applied in the histological classification of ”intimal” sarcoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050396
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  • 103
    Electronic Resource
    Electronic Resource
    Immunohistochemical study of cytochrome P450 2C and 3A in human non-neoplastic and neoplastic tissues (1999)
    Springer
    Virchows Archiv 434 (1999), S. 401-411 
    Details
    ISSN: 1432-2307
    Keywords: Key words Human ; Cytochrome P450 2C ; Cytochrome P450 3A ; Immunohistochemistry ; Neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Organ and cellular distribution and expression constancy of microsomal cytochrome P450 (CYP) 2C and 3A in humans were studied with new polyclonal antibodies to CYP2C (MP-1) and 3A (NF-2) active in formalin-fixed, paraffin-embedded tissues. Antibodies were raised against purified human CYP2C9 and CYP3A4. On western blotting, MP-1 reacted with 2C8, 2C9, 2C18 and 2C19, and NF-2 with 3A4. In both frozen and paraffin sections, hepatocytes showed diffuse immunoreactivity with MP-1 and centrilobular staining with NF-2. Inparaffin sections of 40 kinds of nonneoplastic tissues, epithelium of the small and large intestine, bile duct, nasal mucosa, kidney and adrenal cortex stained positively with both MP-1 and NF-2 antibodies. Epithelium of gastric fundic glands, salivary glands, tracheobronchial glands, Brunner’s glands, the prostate, uterine cervix and nasopharynx showed definite reactivity with MP-1. Epithelium of the gastric mucosa with intestinal metaplasia, duodenum, gallbladder and intercalated ducts of the pancreas and chief cells of the parathyroid and the corpus luteum of the ovary reacted with NF-2. Among the neoplastic tissues, MP-1 reacted with pleomorphic adenoma of the salivary gland and carcinomas of six different organs, and NF-2 with those of 7 different organs. These results indicate that CYP2C and CYP3A are distributed widely and organ specifically, as well as being variably expressed in neoplastic and normal states.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050359
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  • 104
    Electronic Resource
    Electronic Resource
    Nitric oxide synthase in the gastrointestinal tract of the estuarine crocodile, Crocodylus porosus (1999)
    Springer
    Cell & tissue research 296 (1999), S. 433-437 
    Details
    ISSN: 1432-0878
    Keywords: Key words Nitric oxide ; Vasoactive intestinal polypeptide (VIP) ; Immunohistochemistry ; Enteric nervous system ; Crocodylus porosus (Crocodilia)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The aim of this study was to investigate the distribution of nitric oxide synthase (NOS)-containing nerve cells in the gastrointestinal tract of a reptile and to compare it with the pattern in other vertebrate classes. In the estuarine crocodile, Crocodylus porosus, NOS-positive nerve cell bodies and fibres were found in all regions of the gut examined. Most myenteric microganglia contained one or several NOS-immunoreactive neurons together with unlabelled neurons. The majority of the neurons were multipolar, ranging from 10 to 25 µm in diameter. Both the circular and the longitudinal muscle layers were innervated by NOS-immunoreactive nerve fibres, which mostly ran parallel to the muscle fibres. In addition, small blood vessels in the submucosa and on the serosal surface of the gut were innervated by NOS-immunoreactive fibres. Double labelling with antisera to NOS and vasoactive intestinal peptide (VIP) revealed three neuronal subpopulations. A small proportion of the NOS-immunoreactive cells also contained immunoreactivity to VIP while a majority of the VIP-immunoreactive cells were NOS immunoreactive. There were more nerve fibres showing VIP immunoreactivity than fibres with NOS immunoreactivity, although most of the latter also contained immunoreactivity to VIP. VIP-immunoreactive fibres often surrounded the NOS-immunoreactive nerve cells. These results suggest that neuronally released nitric oxide is likely to be involved in the control of gastrointestinal motility in the crocodile as in most other vertebrate species.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051303
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  • 105
    Electronic Resource
    Electronic Resource
    Immunolocalization of hyaluronic acid and inter-alpha-trypsin inhibitor in mice (1999)
    Springer
    Cell & tissue research 296 (1999), S. 587-597 
    Details
    ISSN: 1432-0878
    Keywords: Key words Hyaluronic acid ; Immunohistochemistry ; Inter-alpha-trypsin inhibitor ; Localization ; Mouse (CD-1)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The direct interaction of hyaluronic acid (HA) and heavy chain (HC) of the inter-alpha-trypsin inhibitor (IαI) family plays a critical role in the organization and stabilization of the extracellular matrix. The aim of the present investigation was to elucidate the distribution of the IαI HC and HA in adult mouse tissues. An immunohistochemical method using a rabbit polyclonal antibody raised against mouse IαI heavy-chain peptide and a specific probe for HA (biotinylated HA-binding protein) was used to demonstrate an immunolocalization of IαI HC and HA. Distribution and localization of HA was of three types, namely, colocalization with IαI HC itself (cartilaginous tissue and ovary), localization around IαI HC immunostaining (lung, intestine and skeletal muscle), and localization at a small distance from IαI HC or a different distribution pattern (brain, liver, skin and kidney). These results indicate that IαI HC could function as an HA-rich matrix stabilizer on the cells of cartilage and maturing ovary, in which IαI HC shows colocalization with its predominant ligand, HA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051320
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  • 106
    Electronic Resource
    Electronic Resource
    Differentiation of pinopsin-immunoreactive cells in the developing quail pineal organ: an in-vivo and in-vitro immunohistochemical study (1999)
    Springer
    Cell & tissue research 296 (1999), S. 667-671 
    Details
    ISSN: 1432-0878
    Keywords: Key words Avian pineal organ ; Pinopsin ; Cell differentiation ; Tissue culture ; Immunohistochemistry ; Quail embryo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The avian pineal organ contains several types of photoreceptors with different photopigments: rhodopsin, iodopsin, and pinopsin. We have previously examined the differentiation of both rhodopsin-like and iodopsin-like immunoreactive cells during pineal development in quail embryos to determine the onset of synthesis of specific proteins and their cellular localization. In the present study, we have performed pinopsin immunohistochemistry on in-vivo developing and in-vitro cultured pineal organs of quail embryos. The results were compared with those obtained with rhodopsin and iodopsin immunohistochemistry. In the developing pineal organs, pinopsin immunoreactivity was detected at embryonic day 8, i.e. five days earlier than rhodopsin-like and iodopsin-like immunoreactivities. It was localized exclusively in the protrusions extending into the lumen throughout development, whereas rhodopsin-like and iodopsin-like immunoreactivities were usually found both in cell bodies and processes. These differences were also observed under two different types of culture conditions (dissociated cell culture and organ culture) indicating that, in the avian pineal organ, the expression pattern of the pinopsin gene is basically different from those of the other two pineal photopigments. The present study suggests that pineal cells have a mechanism for the polarized transport of pinopsin molecules.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051326
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  • 107
    Electronic Resource
    Electronic Resource
    The antisecretory factor: synthesis and intracellular localisation in porcine tissues (1999)
    Springer
    Cell & tissue research 296 (1999), S. 607-617 
    Details
    ISSN: 1432-0878
    Keywords: Key words Gastrointestinal tract ; Respiratory tract ; Urogenital tract ; Immunohistochemistry ; In situ hybridization ; mRNA ; Pig (Swedish Landrace × Yorkshire)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The antisecretory factor, AF, is a 41-kDa protein, cloned and sequenced from a human pituitary library. AF is a potent inhibitor of experimental intestinal hypersecretion in rats and pigs. An antiserum against the C-terminal of the truncated, recombinantly produced AF protein was raised in rabbits. The affinity-purified antiserum was used to study the expression of AF in mucosal membranes and in the pituitary gland of the pig; distinctly stained cells were found in lymphoid cells in the connective tissue of all parts of the gastrointestinal, respiratory and urinary tracts. Cytoplasmic AF was demonstrated in endocrine and epithelial cells in the pituitary gland. In situ hybridisation with a digoxigenin-labelled mRNA probe also demonstrated specific cytoplasmic staining in epithelial and lymphoid cells in all of these tissues. The cells stained by either method were similarly distributed topographically within the tissues. The results suggest that a specific defined cell population in these various tissues possesses the capability of both synthesising and storing the AF protein within the cellular cytoplasmic compartment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051322
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  • 108
    Electronic Resource
    Electronic Resource
    Expression of vascular endothelial growth factor (VEGF) and its receptors during embryonic implantation in the golden hamster (Mesocricetus auratus) (1999)
    Springer
    Cell & tissue research 296 (1999), S. 339-349 
    Details
    ISSN: 1432-0878
    Keywords: Key words Vascular endothelial growth factor ; flt-1 ; flk-1 ; Embryonic implantation ; Immunohistochemistry ; In situ hybridization ; Reverse transcription/polymerase chain reaction ; Golden hamster (Mesocricetus auratus)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Expression of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) and its receptors (flt-1 and flk-1) during the peri-implantation period (days 3, 4, 5, 6 and 7 post coitus) in the golden hamster was investigated by in situ hybridization, immunohistochemistry and the reverse transcription/polymerase chain reaction (RT-PCR). Three days after mating, in situ hybridization and immunohistochemical staining revealed weak VEGF expression only in the uterine epithelium; this expression was similar to that seen at oestrus. Flt-1 but no flk-1 immunoreactivity was observed. At day 4, the subepithelial stroma and embryo displayed immunoreactivity for VEGF and flt-1, whereas endothelial cells expressed both flt-1 and flk-1. At day 5, immunoreactivity for both VEGF and its receptors was detected in decidual cells and vascular endothelial cells. Only a few embryonic cells expressed VEGF mRNA but strong signals were noted in decidual cells. The patterns of VEGF and VEGF receptor expression were the same in the day-6 and day-7 embryos and decidua, except for an increase in intensity as development progressed. Based on these findings, we conclude that, in addition to its known actions on endometrial angiogenesis and tissue swelling, VEGF may also facilitate the proliferation and differentiation of the endometrium and help to sustain the avascular embryo during this early stage of development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051294
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  • 109
    Electronic Resource
    Electronic Resource
    Elongated pericyte-like cells connect discrete capillaries in the cochlear stria vascularis of gerbils and rats (1999)
    Springer
    Cell & tissue research 296 (1999), S. 673-676 
    Details
    ISSN: 1432-0878
    Keywords: Key words Basal lamina ; Immunohistochemistry ; Confocal laser microscopy ; Cochlea ; Mongolian gerbil ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Bridging structures between discrete capillaries in the stria vascularis of the cochlea were studied morphologically in gerbils and rats. Serial thin sections for transmission electron microscopy revealed (1) that elongated cells surrounded by the basal lamina provided the structural basis for the bridging structure, (2) that the basal lamina surrounding the elongated cell extended to the basal lamina around the capillary endothelial cell, (3) that the electron density of the cytoplasm was similar to that of the pericytes around the capillaries, and (4) that the cell was attached to the capillaries at both ends only. Visualization of the basal lamina by immunofluorescent methods revealed (1) that capillaries were often bent at the site of attachment of the bridging cell, (2) that the bridging cell bifurcated occasionally, and (3) that the density of the bridging cell was much higher in the stria vascularis than in the underlying spiral ligament. Filamentous actin visualized by fluorescent phalloidin was not apparent in the bridging cell. We propose that the bridging cell provides mechanical strength to the tortuous capillary network in the stria vascularis and participates in the specific function of the stria vascularis in cooperation with other types of cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051327
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  • 110
    Electronic Resource
    Electronic Resource
    Immunohistochemical evidence for the presence of tryptophan hydroxylase and serotonin in the rodent Harderian gland (1999)
    Springer
    Cell & tissue research 296 (1999), S. 517-523 
    Details
    ISSN: 1432-0878
    Keywords: Key words Harderian gland ; Tryptophan hydroxylase ; Serotonin ; Immunohistochemistry ; Rat (Wistar) ; Syrian hamster ; Mesocricetus auratus ; Djungarian hamster ; Phodopus sungorus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The Harderian gland is considered as being an extrapineal source of melatonin. In most rodents, the Harderian gland contains two epithelial cell types (I and II). The aim of this study has been to define which cell type is involved in indoleamine synthesis. The presence and localization of serotonin (melatonin precursor) and tryptophan hydroxylase (the rate-limiting enzyme for serotonin synthesis) have been investigated by immunohistochemistry in male Wistar rats, Syrian hamsters and Djungarian hamsters. The results of the present study show that immunoreactivity for tryptophan hydroxylase and serotonin is confined to the type I cell, suggesting that this cell type is involved in indoleamine synthesis in the rodent Harderian gland.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051312
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  • 111
    Electronic Resource
    Electronic Resource
    Differential expression of nitric oxide synthases in EGF-responsive mouse neural precursor cells (1999)
    Springer
    Cell & tissue research 296 (1999), S. 489-497 
    Details
    ISSN: 1432-0878
    Keywords: Key words Nitric oxide synthase isoforms I ; III ; Neurosphere ; Immunohistochemistry ; Nestin ; Embryonic brain striatum ; Mouse (Balb/c)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Nitric oxide (NO) is a gaseous, radical molecule that plays a role in various physiological processes in the nervous system such as learning and hippocampal plasticity. It is generated from l-arginine by nitric oxide synthases (NOS), which come in three isoforms depending on the tissue of origin, namely inducible-NOS (iNOS in macrophages), endothelial-NOS (eNOS in endothelial cells) and neural-NOS (nNOS in neural cells). We used epidermal growth factor (EGF)-responsive nestin-positive neural precursor cells originating from the mouse E16 embryonic striatum, and studied the relative expression of NOS isoforms probed with isoform-specific antibody using the avidin-biotin immunohistochemical method. Our data revealed both nNOS and eNOS to be expressed in both neurospheres and desegregated neural precursor cells. However, iNOS signals were virtually undetectable in both cell categories. When the neural precursor cells were carried in the presence of poly-l-ornithine (PLO), there was a strong induction of the expression of iNOS proteins, indicating the possibility that this isoform is amenable to modulation by extracellular cues. These preliminary results suggest both nNOS and eNOS to be important in the physiology of neural precursor cells, and that iNOS might also play a role at certain stages in the life of these cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051309
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  • 112
    Electronic Resource
    Electronic Resource
    P2X receptors in the rat duodenal villus (1999)
    Springer
    Cell & tissue research 297 (1999), S. 111-117 
    Details
    ISSN: 1432-0878
    Keywords: Key words P2X receptor ; Immunohistochemistry ; Duodenum ; Rat (Sprague Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Immunohistochemical techniques were performed on freshly frozen sections of the duodenum of the rat using specific polyclonal antibodies to unique peptide sequences of P2X1–7 receptors. Of the antibodies to the seven known P2X receptor subtypes that mediate extracellular signalling by nucleotides, three reacted with discrete structures in the duodenal villus of the rat. Anti-P2X1 reacted with the capillary plexus in the intestinal villus, which did not extend to the crypt region, suggesting that nucleotides may be involved in the uptake and transport of metabolites. Anti-P2X5 immunostained the membranes of the narrow ”stem” of villus goblet cells, where the nucleus and cell organelles reside, possibly influencing synthesis and release of mucins. P2X7 receptor immunoreactivity was only seen in the membranes of enterocytes and goblet cells at the tip of the villus, where cells are exfoliated into the lumen, consistent with earlier findings that P2X7 is involved in apoptotic events. Thus, in complex structures such as the intestinal villus, purinoceptors appear to participate in several and diverse signalling functions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051338
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  • 113
    Electronic Resource
    Electronic Resource
    Ultrastructure and distribution dynamics of chloride cells in tilapia larvae in fresh water and sea water (1999)
    Springer
    Cell & tissue research 297 (1999), S. 119-130 
    Details
    ISSN: 1432-0878
    Keywords: Key words Chloride cells (mitochondria-rich cells) ; Teleost larvae ; Osmoregulation ; Immunohistochemistry ; Quantification ; Ultrastructure ; Oreochromis mossambicus (Teleostei)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Integumental and branchial chloride cells of tilapia larvae (Oreochromis mossambicus) were studied at the light-microscopical and ultrastructural level. Total numbers and distribution of chloride cells were quantified after immunostaining of cross sections of the entire larvae with an antibody against the α-subunit of Na+/K+-ATPase. The majority (66%) of Na+/K+-ATPase-immunoreactive (ir) cells, i.e. chloride cells, of freshwater tilapia larvae were located extrabranchially up to 48 h after hatching. Five days after hatching, the majority (80%) of chloride cells were found in the buccal cavity. Transfer of 24-h-old larvae to 20% sea water speeded up this process; 24 h after transfer (i.e. 48 h after hatching), the majority (59%) of chloride cells were located in the buccal cavity. The branchial chloride cell population of 24-h- and 120-h-old larvae consisted of immature, mature, apoptotic and necrotic chloride cells. However, relatively more immature chloride cells were observed in freshwater larvae (42–63%) than in (previously studied) freshwater adults (21%), illustrating the developmental state of the gills. After transfer to sea water, the incidence of degenerative chloride cells did not change. Furthermore, the incidence of immature cells had decreased and a new subtype of chloride cells, the ”mitochondria-poor” cells, appeared more frequently. These mitochondria-poor chloride cells were characterised by an abundant tubular system and relatively few mitochondria, which were aligned at the border or concentrated in one part of the cytoplasm. Most of these cells did not contact the water. The function of their enhanced appearance after seawater transfer is unknown.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051339
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  • 114
    Electronic Resource
    Electronic Resource
    Differential distribution of somatostatin sst2 receptor splice variants in rat gastric mucosa (1999)
    Springer
    Cell & tissue research 297 (1999), S. 163-168 
    Details
    ISSN: 1432-0878
    Keywords: Key words Acid release ; Stomach ; Antibody ; Immunohistochemistry ; Rat (Sprague Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The tetradecapeptide somatostatin (SRIF) has an inhibitory action on acid secretion in the stomach. It has been suggested that somatostatin may act directly on parietal cells as well as indirectly via histamine-producing cells. A family of high affinity membrane-bound receptors, which are termed sst1–sst5 receptors, mediates the physiological effects of somatostatin. On the basis of functional studies it has been suggested that somatostatin may mediate its actions in the stomach by activation of a somatostatin sst2 receptor type. Two splice variants of the rat sst2 receptor exist, sst2(a) and sst2(b), which differ in length and composition of their intracellular carboxy termini. To date, little information is available on the distribution of the somatostatin sst2(b) receptor in any peripheral tissue. Here we show for the first time the localisation of this receptor isoform in the rat oxyntic mucosa, where the receptor protein was found to be present in parietal cells. This is in contrast to sst2(a) receptor, which was localised to enterochromaffin-like cells and nerve fibres. The differential localisation of the receptor isoforms to two key cell types, parietal cells and enterochromaffin-like cells, may explain how somatostatin inhibits acid secretion by more than one mechanism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051344
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  • 115
    Electronic Resource
    Electronic Resource
    Immunohistochemical localization of calbindin D28k during root formation of rat molar teeth (1999)
    Springer
    Cell & tissue research 297 (1999), S. 503-512 
    Details
    ISSN: 1432-0878
    Keywords: Key words Calbindin ; Hertwig’s epithelial root sheath ; Epithelial rest of Malassez ; Preodontoblast ; Periodontal fibroblast ; Immunohistochemistry ; Rat (Sprague Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The present study was undertaken to examine the localization of calbindin D28k (CB)-like immunoreactivity (-LI) during the root formation of the rat molar. In the adult rat, CB-LI was detected in some of the cells of the epithelial rest of Malassez at the bifurcational region and in certain cells between the root dentin and cementum at the apical region. These cells had indented nuclei and many tonofilaments, and cementocytes lacked CB-LI. Moreover, CB-LI was observed in the periodontal fibroblasts in the alveolar half of the apical region. During root formation, the cells in the Hertwig’s epithelial root sheath (HERS) lacked CB-LI, but most fragmented cells along the root surface began to express CB-LI when HERS was disrupted. Preodontoblasts and odontoblasts at the apical portion of the root also showed CB-LI. After the formation of cellular cementum, the CB-immunoreactive (-IR) cells were entrapped between the root dentin and cementum in the apical portion of the root. The number of CB-IR cells at the root surface decreased gradually, while that between the root dentin and cementum increased. The fibroblasts in the periodontal ligament began to express CB-LI after commencement of the occlusion, and the number and the staining intensity of CB-IR fibroblasts increased gradually with the passage of time. The present results suggest that CB may play an important role in the survival of the epithelial cells, in the cellular responses of periodontal fibroblasts against mechanical forces caused by the occlusion, and in the initial mineralization by the odontoblasts through the regulation of intracellular Ca2+ concentration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051377
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  • 116
    Electronic Resource
    Electronic Resource
    Motor innervation by enteric nerve fibers containing both nitric oxide synthase and galanin immunoreactivities in the striated muscle of the rat esophagus (1999)
    Springer
    Cell & tissue research 295 (1999), S. 241-245 
    Details
    ISSN: 1432-0878
    Keywords: Key words Enteric innervation ; Immunohistochemistry ; Nitric oxide synthase ; Galanin ; Striated muscle ; Esophagus ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The relationship between nitric oxide synthase (NOS)- and galanin-immunoreactive nerve terminals and the origin of NOS-immunoreactive nerve terminals on the motor endplates in the striated muscles of the rat esophagus was investigated. Double immunohistochemical staining revealed a dual innervation of motor endplates by calcitonin gene-related peptide (CGRP)-immunoreactive axons and by axons that were immunoreactive for both NOS and galanin. On average, 91% of NOS terminals were galanin immunoreactive. NOS-immunoreactive fibers were revealed at 67% of endplates, identified by the presence of CGRP terminals. The left vagus and superior laryngeal nerve were cut and 15 days allowed for terminals to degenerate. This caused a significant loss of CGRP fibers, but did not affect the density of innervation of the striated muscle by NOS-immunoreactive fibers. Thus the NOS/galanin fibers are deduced to originate from ganglia in the esophageal wall. This is supported by our observation of numerous NOS-immunoreactive nerve cell bodies in the myenteric ganglia of the esophagus, 74% of which were galanin immunoreactive. There were no CGRP-immunoreactive nerve cell bodies in the wall of the esophagus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051230
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  • 117
    Electronic Resource
    Electronic Resource
    Serotonin-like immunoreactivity in the stomatogastric nervous systems of crayfishes from four genera (1999)
    Springer
    Cell & tissue research 295 (1999), S. 537-551 
    Details
    ISSN: 1432-0878
    Keywords: Key words Decapod ; Invertebrate ; Monoamine ; Immunohistochemistry ; Procambarus clarkii ; Pacifastacusleniusculus (Crustacea)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We used whole-mount immunocytochemistry to characterize the distribution of serotonin in the stomatogastric nervous systems of seven species of crayfish representing three genera from the family Cambaridae (Orconectes, Cambarus, and Procambarus) and one from the family Astacidae (Pacifastacus). In all species, we observed serotonin-like immunoreactivity in four gastropyloric receptor (GPR) neurons located in the lateral ventricular nerves, with one pair of neurons in each nerve. As in other crustaceans, the GPR axons project to the stomatogastric ganglion and to the bilateral commissural ganglia. In three crayfishes, we observed the GPR axons crossing the commissural ganglia, and extending toward the thoracic nervous system. This feature was most clearly and consistently seen in Pacifastacus leniusculus. The number of stained somata in the commissural ganglia varied among crayfish species from two (in Procambarus clarkii) to five (in Pacifastacus leniusculus). The largest soma (the L cell) displayed both serotonin- and tyrosine hydroxylase-like immunoreactivity in all species, suggesting that serotonin and dopamine are cotransmitters in this cell. The inferior esophageal nerve and a branch of this nerve (the inner labral nerve) contained several axons with serotonin-like immunoreactivity. These axons were clearly present in only one species (Procambarus clarkii). Serotonin acts as a neuromodulator of rhythms produced by circuits in the crab and lobster stomatogastric ganglion, and is likely to play a similar role in crayfish. Differences are apparent in the distribution of serotonin among crayfish species and between crayfish and other crustaceans, and could result in differences in the physiological action of this modulator.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051259
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  • 118
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    Immunohistochemical localization and biochemical characterization of two novel decapeptides derived from POMC-A in the trout hypothalamus (1999)
    Springer
    Cell & tissue research 295 (1999), S. 409-417 
    Details
    ISSN: 1432-0878
    Keywords: Key words Proopiomelanocortin ; Post-translational processing ; Novel neuropeptides ; Immunohistochemistry ; HPLC analysis ; Oncorhynchus mykiss (Teleostei)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Several vertebrate species which underwent duplication of their genome, such as trout, salmon and Xenopus, possess two proopiomelanocortin (POMC) genes. In the trout, one of the POMC molecules, called POMC-A, exhibits a unique C-terminal extension of 25 amino acids which has no equivalent in other POMCs characterized so far. This C-terminal peptide contains three pairs of basic residues, suggesting that it may be the source of novel regulatory peptides. The aim of the present study was to investigate the occurrence of these peptides in the brain of the trout Oncorhynchus mykiss by using specific antibodies raised against two epitopes derived from the C-terminal extension of POMC-A, i.e., EQWGREEGEE and YHFQ-NH2. Immunohistochemical labeling of brain sections revealed the presence of EQWGREEGEE- and YHFQ-NH2-immunoreactive cell bodies in the anterior part of the nucleus lateralis tuberis of the hypothalamus. Immunoreactive fibers were observed in the dorsal hypothalamus, the thalamus, the telencephalon, the optic tectum and the medulla oblongata. In contrast, no labeling was detected using antibodies against the non-amidated peptide YHFQG. Biochemical characterization was performed by combining high-performance liquid chromatography (HPLC) analysis with radioimmunoassay (RIA) quantification. Two peptides exhibiting the same retention time as synthetic EQWGREEGEE and ALGERKYHFQ-NH2 were resolved. However, no peptide co-eluting with YHFQ-NH2 or YHFQG could be detected. These results demonstrate that, in the trout brain, post-translational processing of POMC-A generates the two decapeptides EQWGREEGEE and ALGERKYHFQ-NH2. The wide distribution of immunoreactive fibers in the diencephalon, telencephalon, optic tectum and medulla oblongata suggests that these peptides may exert neurotransmitter and/or neuromodulator activities.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051247
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  • 119
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    Localization of leech excitatory peptide, a member of the GGNG peptides, in the central nervous system of a leech (Whitmania pigra) by immunohistochemistry and in situ hybridization (1999)
    Springer
    Cell & tissue research 297 (1999), S. 155-162 
    Details
    ISSN: 1432-0878
    Keywords: Key words Central nervous system ; Immunohistochemistry ; In situ hybridization ; Leech excitatory peptide ; Neuropeptide ; Whitmania pigra (Annelida)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  We have recently isolated a myoactive peptide, called leech excitatory peptide, belonging to the GGNG peptide family from two species of leeches, Hirudo nipponia and Whitmania pigra. Immunohistochemistry and in situ hybridization were employed to localize leech excitatory peptide-like peptide(s) and its gene expression in the central nervous system of W. pigra. A pair of neuronal somata were stained by both immunohistochemistry and in situ hybridization in the supraesophageal, subesophageal, and segmental ganglia. In addition, several other neurons showed positive signals by either immunohistochemistry or in situ hybridization in these ganglia. An immunoreactive fiber was observed to run in the anterior root of segmental ganglion 6, which is known to send axons to the sexual organs, though we failed to detect immunoreactivity in possible target tissues. Antiserum specificity was established by enzyme-linked immunosorbent assay using different leech excitatory peptide-related peptides. Leech excitatory peptide elicited muscular contraction of isolated preparations of penis and intestine at concentrations of 10–8 M. These results suggest that leech excitatory peptide is a neuropeptide modulating neuromuscular transmission in multiple systems, including regulation of reproductive behavior.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051343
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  • 120
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    Cellular localization and distribution of glucocorticoid receptor immunoreactivity and the expression of glucocorticoid receptor messenger RNA in rat pituitary gland (1999)
    Springer
    Cell & tissue research 295 (1999), S. 207-214 
    Details
    ISSN: 1432-0878
    Keywords: Key words Glucocorticoid receptor (GR) ; Immunohistochemistry ; In situ hybridization ; Pituitary ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract By means of double immunohistochemical techniques and a nonradioisotopic in situ hybridization method, we determined the colocalization pattern of glucocorticoid receptor (GR) and pituitary hormones and the GR messenger RNA (mRNA) expression in the pituitaries of Wistar adult male rats. Immunoreactivity for GR was detected in the nuclei of cells in the anterior and posterior pituitary. Double immunohistochemistry revealed that the colocaliza- tion of GR and anterior pituitary hormones occurred in almost 99% of the growth hormone (GH)-producing cells and adrenocorticotropic hormone (ACTH)-producing cells, and in 67% of the thyroid stimulating hormone (TSH)-producing cells. Almost all of the folliculostellate cells (93%), marginal layer cells (94%) in the anterior pituitary, and pituicytes (96%) in the posterior pituitary immunostained for S100 protein antibody were also immunostained with GR. GR mRNA was abundant in the cytoplasm of anterior and intermediate pituitary cells but scattered sparsely in that of the posterior pituitary. These results suggest that glucocorticoids directly influence certain pituitary cells in order to regulate cell function, including the synthesis and/or secretion of hormones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051226
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  • 121
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    Vessel size-dependent expression of intermediate-sized filaments, calponin, and h-caldesmon in smooth muscle cells of human coronary arteries (1999)
    Springer
    Heart and vessels 14 (1999), S. 253-261 
    Details
    ISSN: 1615-2573
    Keywords: Smooth muscle cell ; Heterogeneity ; Coronary artery ; Human ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The arterial media is composed of a heterogeneous population of smooth muscle cells (SMCs). Recently, the properties of SMCs were observed to be heterogeneous not only among individual cells but also among arteries of the same vascular bed. To test the hypothesis that a site-specific heterogeneity exists in the SMCs of human coronary arteries, we examined the expression of desmin, vimentin, calponin, and high-molecular-weight (h-) caldesmon in arteries of various sizes. Specimens of arteries were obtained at autopsy from 12 patients: 6 adults (67 ± 4 years old); 3 younger adults (26 ± 2 years old); and 3 neonates. The size of the arteries was estimated by the number of SMC layers of the media. The expression was compared in SMCs of large arteries (〉10 layers in adults, 〉5 layers in neonates), medium-sized arteries (5–10 layers in adults, 3–5 SMC layers in neonates), and small arteries (〈3 layers). In adults, the percentage of arteries positive for desmin was lower in the small (17% ± 3%) and medium-sized arteries (44% ± 12%) than in the large arteries (94% ± 6%) (P 〈 0.01). The percentage of arteries positive for calponin was also lower in the small (18% ± 2%) and medium-sized arteries (66% ± 5%) than in the large arteries (100%) (P 〈 0.01). The percentage for vimentin and h-caldesmon did not differ among large, medium-sized, and small arteries. These observations in adults were similar to those in younger adults or neonates. The phenotypes of medial SMCs are vessel sizedependent in human coronary arteries. This finding should be important for understanding the site-specific characteristics of vascular function in the regulation of myocardial perfusion or those of vascular responses to environmental changes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01747855
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  • 122
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    Pathological investigation of sentinel lymph nodes (1999)
    Springer
    European journal of nuclear medicine 26 (1999), S. S43 
    Details
    ISSN: 1619-7089
    Keywords: Key words: Sentinel lymph node ; Frozen section ; Imprint cytology ; Immunohistochemistry ; Polymerase chain reaction ; Flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The sentinel lymph-node procedure enables selective targeting of the first draining lymph node, where the initial metastases will form. A negative sentinel node (SN) predicts the absence of tumour metastases in the other regional lymph nodes with high accuracy. This means that in the case of a negative SN, regional lymph-node dissection is no longer necessary. Besides saving costs, this will prevent many side-effects as a result of lymph-node dissection. The task of the pathologist is to screen SNs for metastases. To this end, several techniques are available such as standard histo- and cytopathological techniques, immunohistochemistry, flow cytometry, and molecular biological techniques. These methods are explained and their sensitivity for detecting SN metastases is discussed. Some of these techniques also appear to be useful for intra-operative evaluation of SNs. The standard protocol for detection of SN metastases consists of extensive histopathological investigation including step H&E stained sections and immunohistochemistry. Intra-operative frozen-section analysis of SNs has been shown to be reliable for breast-cancer axillary lymph nodes. In the intra-operative setting, imprint cytology can also be used but its additional value to frozen section analysis is not yet clear. Further studies are necessary to establish the role of sophisticated molecular biological techniques such as reverse transcription polymerase chain reaction (RT-PCR) in detecting SN metastases. The sensitivity of flow cytometry is too low for this purpose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002590050577
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  • 123
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    Protein Kinase C Targeting in Antineoplastic Treatment Strategies (1999)
    Springer
    Investigational new drugs 17 (1999), S. 227-240 
    Details
    ISSN: 1573-0646
    Keywords: apoptosis ; protein kinase C ; sphingoid bases ; safingol ; diglyceride ; bryostatin 1 ; staurosporine ; 7-hydroxy staurosporine (UCN-01) ; 4′-N-benzoyl staurosporine (CGP-41251) ; calphostin C (UCN-1028c)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Neoplastic cell survival is governed by a balance between pro-apoptotic and anti-apoptotic signals. Noteworthy among several anti-apoptotic signaling elements is the protein kinase C (PKC) isoenzyme family, which mediates a central cytoprotective effect in the regulation of cell survival. Activation of PKC, and subsequent recruitment of numerous downstream elements such as the mitogen-activated protein kinase (MAPK) cascade, opposes initiation of the apoptotic cell death program by diverse cytotoxic stimuli. The understanding that the lethal actions of numerous antineoplastic agents are, in many instances, antagonized by cytoprotective signaling systems has been an important stimulus for the development of novel antineoplastic strategies. In this regard, inhibition of PKC, which has been shown to initiate apoptosis in a variety of malignant cell types, has recently been the focus of intense interest. Furthermore, there is accumulating evidence that selective targeting of PKC may prove useful in improving the therapeutic efficacy of established antineoplastic agents. Such chemosensitizing strategies can involve either (a) direct inhibition of PKC (e.g., following acute treatment with relatively specific inhibitors such as the synthetic sphingoid base analog safingol, or the novel staurosporine derivatives UCN-01 and CGP-41251) or (b) down-regulation (e.g., following chronic treatment with the non-tumor-promoting PKC activator bryostatin 1). In preclinical model systems, suppression of the cytoprotective function(s) of PKC potentiates the activity of cytotoxic agents (e.g., cytarabine) as well as ionizing radiation, and efforts to translate these findings into the clinical arena in humans are currently underway. Although the PKC-driven cytoprotective signaling systems affected by these treatments have not been definitively characterized, interference with PKC activity has been associated with loss of the mitogen-activated protein kinase (MAPK) response. Accordingly, recent pre-clinical studies have demonstrated that pharmacological disruption of the primary MEK-ERK module can mimic the chemopotentiating and radiopotentiating actions of PKC inhibition and/or down-regulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006328303451
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  • 124
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    Activation-Induced Apoptosis of Peripheral Lymphocytes Treated with 7-Hydroxystaurosporine, UCN-01 (1999)
    Springer
    Investigational new drugs 17 (1999), S. 335-341 
    Details
    ISSN: 1573-0646
    Keywords: UCN-01 ; IL-2 receptor ; Fas ; Fas-ligand ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract 7-hydroxystaurosporine (UCN-01) is a new anticancer agentwhich exerts an inhibitory effect on cell cycle check points andis currently under phase I clinical trials in US and Japan.Preliminary clinical data indicated that UCN-01 remained inplasma at high concentrations for long periods of time. Thisunavoidable high plasma drug exposure is likely to lead tohematological toxicities in patients. In the present study,cultured human peripheral blood lymphocytes (PBLs) were used toevaluate the possible hematological toxicities of UCN-01treatment. UCN-01 induces apoptosis, and the induction ofapoptosis-related surface markers were also examined toinvestigate the involvement of these molecules in UCN-01-inducedapoptosis in PBLs. in vitroviability of PBLs wasdecreased by high dose of UCN-01 (25 μM, 3-day exposure). Thiseffect of UCN-01 was significantly suppressed by the presence ofhuman serum, suggesting that some specific inhibitory factor(s)in human serum may antagonize the lympholytic effect of UCN-01.The percentage of annexin V-positive PI-negative cells increasedwith exposure to UCN-01 in a time- and dose-dependent manner; byup to 30.3% after exposure to 25 μM UCN-01 for 3 days.At the same time, the expression of both interleukin-2 receptor(IL-2R, CD25) and Fas (CD95), analyzed by flow cytometry, wasinduced. Con A-stimulated PBLs were more sensitive toUCN-01-induced apoptosis than non-stimulated lymphocytes andUCN-01 increased the sFas-L released into culture medium from conA-stimulated PBLs. Therefore, lymphocyte depletion mediated byactivation-induced apoptosis is likely to occur in patientstreated with UCN-01 at high doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006374118879
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  • 125
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    Influence of bcl-2 on antibody productivity in high cell density perfusion cultures of hybridoma (1999)
    Springer
    Cytotechnology 30 (1999), S. 95-106 
    Details
    ISSN: 1573-0778
    Keywords: apoptosis ; Bcl-2 ; fixed-bed ; hollow fibre ; hybridoma ; perfusion ; protein-free medium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Apoptosis is an active, genetically determined death mechanism which can be induced by a wide range of physiological factors and by mild stress. It is the predominant form of cell death during the production of antibodies from murine hybridoma cell lines. A number of studies have now demonstrated that the suppression of this death pathway, by means of over-expression of survival genes such as bcl-2, results in improved cellular robustness and antibody productivity during batch culture. In the present study, the influence of bcl-2 expression on hybridoma productivity in two high density perfusion bioreactor systems was investigated. In the first system, a fixed-bed reactor, the DNA content in the spent medium was 25% higher in the control (TB/C3-pEF) culture than that found in the bcl-2 transfected (TB/C3-bcl2) cultures at all perfusion rates. This is indicative of a higher level of cell death in the control cell line. The average antibody concentration for the TB/C3-pEF cell line was 14.9 mg L-1 at perfusion rates of 2.6 and 5.2 d-1. However, for the TB/C3-bcl2 cell line it was 33 mg L-1 at dilution rates of 2 and 4 d-1. A substantial increase in antibody concentration was also found in the Integra Tecnomouse hollow fibre reactor. The antibody titre in the TB/C3-bcl2 cassette was nearly 100% higher than that in the TB/C3-pEF cassette during the cultivation period which lasted 6 weeks. Clearly, these results demonstrate the positive impact of bcl-2 over-expression on production of antibody in hybridoma perfusion cultures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008055702079
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  • 126
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    Co-expression of bcl-2 and bag-1, apoptosis suppressing genes, prolonged viable culture period of hybridoma and enhanced antibody production (1999)
    Springer
    Cytotechnology 31 (1999), S. 143-151 
    Details
    ISSN: 1573-0778
    Keywords: antibody productivity ; apoptosis ; BAG-1 ; Bcl-2 ; cell survival ; hybridoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Human bcl-2 and bag-1 DNA were introduced into mouse hybridoma 2E3- O cells and expressed. The expression of bcl-2 in BCMGneo-bcl2 transfectants was confirmed by ELISA and that of bag-1 in pZeo-bag1 was confirmed by western blotting. In batch cultures, the over-expression of bcl-2 prolonged the culture period by 2 days and co-expression of bcl-2 and bag-1 prolonged the culture period by 3 days. The delayed increase in the dead cell number in culture of the bcl-2 and bag-1 cotransfectant indicated the additional antiapoptosis effect of bcl-2 and bag-1 cotransfection in comparison with the bcl-2 only transfection. The bcl-2 transfectants (2E3O-Bcl2) produced antibody twofold per batch culture in comparison with 2E3-O cells transfected with BCMGSneo (2E3O-Mock). Enhancement of this MoAb production was due to the improved survival of the cells and was not due to stimulation of antibody production rate per cell by Bcl-2 expression. And the bcl-2 and bag-1 co-transfectant (2E3O-Bcl2-BAG1) produced antibody approximately fourfold of 2E3O-Mock per batch culture. Enhancement of this MoAb production was due to the improved survival of the cells and was partly due to stimulation of MoAb production rate per cell in the non-growing phase by the cotransfection. The method to engineer hybridoma cells genetically with bcl-2 and bag-1 for increasing viability and productivity would be widely applied for improving antibody productivity of hybridoma cultures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008080407581
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    A novel 96-well scintillation proximity assay for the measurement of apoptosis (1999)
    Springer
    Cytotechnology 31 (1999), S. 271-282 
    Details
    ISSN: 1573-0778
    Keywords: annexin V ; Apo-2 ligand ; apoptosis ; Cytostar-T® scintillating microplates ; flow cytometry ; lymphotoxin (LT)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The translocation of phospholipids across the plasma membrane has been widely documented as one of the earliest measurable biochemical events of apoptosis. Using fluorescently labelled annexin V, which preferentially binds phosphatidylserine (PS) in the presence of Ca2+, the externalization of PS can be measured and apoptosis quantified using flow cytometry. Conventional detection methods utilizing annexin V, while faster than in situ DNA end-labelling or DNA laddering, require extensive sample preparation which may compromise samples and makes rapid, high volume screening prohibitive. This paper describes a novel assay for the measurement of apoptosis based upon binding of radiolabelled annexin V to apoptotic cells attached to the growth surface of a 96-well scintillating microplate (Cytostar-T®). We compared measurements of apoptosis made by flow cytometry to those obtained with the scintillating microplate in three model systems, treatment of: mouse connective tissue (L-M) cells with lymphotoxin (LT), human lung carcinoma (H460) cells with Apo-2 ligand and human umbilical vein endothelial (HUVE) cells with staurosporine. In this assay, we compare both direct and indirect labelling methods by utilizing either iodinated annexin V or biotinylated annexin V/[35S] streptavidin to radiolabel apoptotic cells. The signal detected is a direct consequence of the binding of annexin V to externalized PS on apoptotic cells and the proximity of the label to the base of the plate. Using this method, separation of bound and unbound radiolabel signal occurs directly within the well resulting in a sensitive assay that requires minimal manipulation and can accomodate a large number of samples.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008053320396
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  • 128
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    Apoptosis in Cardiac Diseases—New Opportunities for Novel Therapeutics for Heart Diseases (1999)
    Springer
    Cardiovascular drugs and therapy 13 (1999), S. 289-294 
    Details
    ISSN: 1573-7241
    Keywords: heart failure ; apoptosis ; protein kinases ; caspases ; DNA damage ; cardiomyocytes ; β-blocks
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Apoptosis as defined by contemporary science describes a form of cell death that involves discrete genetic and molecular programs, de novo protein expression and unique cellular phenotype. Evidence for the existence of apoptosis in the human heart has been reported in various cardiac diseases, including ischemic and non-ischemic heart failure, myocardial infarction and arrhythmias. Among the most potent stimuli that elicit cardiomyocyte apoptosis are: oxygen radicals (including NO), cytokines, (FAS/TNFα family of cytokines) and growth factors/energy deprivation. Several complex signal transduction pathways have been implicated in execution of cardiomyocyte apoptosis, including: Fas/TNFα receptors signaling, stress or mitogen activated protein kinases (SAPK/MAPK), sphingolipids metabolites (ceramide), G-protein coupled receptor (GPCR) signaling (Gαi, Gαq) and NFkB activation. Apoptosis of cardiac myocytes may contribute to progressive pump-failure, arrhythmias and cardiac remodeling. The recognition of numerous molecular targets associated with cardiomyocyte apoptosis that are amenable for pharmacologic manipulation, may provide novel therapeutic strategies for diverse cardiac ailments, as recently suggested by pharmacologic studies in experimental animals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007735413477
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    Control of Proliferation and Survival of C6 Glioma Cells with Modification of the Nerve Growth Factor Autocrine System (1999)
    Springer
    Journal of neuro-oncology 41 (1999), S. 121-128 
    Details
    ISSN: 1573-7373
    Keywords: apoptosis ; cell death ; C6 glioma ; nerve growth factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nerve growth factor (NGF) plays an important physiological role in differentiation and survival of various types of neurons. Glial cells and glial tumor cells synthesize multiple neurotrophic factors including NGF and secrete them into the surrounding environment; however, the mechanisms of NGF and the significance of NGF receptors have not been studied in detail. The C6 glioma cell line can synthesize NGF, respond to exogenous application of NGF and stimulate the expression of NGF receptor in an autocrine manner. In order to determine the significance of such an NGF autocrine system, the effects of exposure to exogenous NGF and deprivation of endogenous NGF were examined in a C6 glioma cell line in vitro. Exogenous NGF significantly inhibited maintenance of the cell number and thymidine incorporation. Morphological changes, including the formation of growth cones, outgrowth of processes and cellular hypertrophy, were observed, concurrently, indicating that exogenous NGF stimulated differentiation and thereby inhibited proliferation of the cells. Deprivation of endogenous NGF with anti-NGF antibody elicited a rapid decrease in cell number and thymidine incorporation, and led almost all of the cells to death within 8 days. The protein synthesis inhibitor, cycloheximide, strongly inhibited the death of NGF-deprived cells, suggesting the involvement of an active process requiring synthesis of suicide proteins. These findings imply that the NGF autocrine system plays a significant role in regulating the differentiation and survival of C6 glioma cells, similarly to neuronal cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006127624487
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    Participation of Bcl-2/Bax-α in Glutamate-induced Apoptosis of Human Glioblastoma Cells (1999)
    Springer
    Journal of neuro-oncology 44 (1999), S. 109-117 
    Details
    ISSN: 1573-7373
    Keywords: glutamate ; glioblastoma ; apoptosis ; Bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Glutamate has been shown to function as a toxic agent in neuronal and glial cells, as well as an excitatory neurotransmitter throughout the central nervous system. In the present study, we examined the effect of increasing glutamate concentration on the induction of apoptosis in the two human glioblastoma cell lines GB-4 and GB-12. Glutamate exposure caused cell death of GB-4 and GB-12 in a dose-dependent manner. The cells were found to die via apoptosis in response to glutamate based on the following criteria: propidium iodide (PI) staining, H–E staining, electron microscopic analysis, and the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. The glutamate-induced apoptosis appears to involve the modulation of Bcl-2 family gene products such as Bcl-2, Bcl-xL, and Bax-α. Both Bcl-2 and Bcl-xL were down-regulated by glutamate at 24 h and further at 48 h. The apoptosis-promoting product p21 Bax-α was also down-regulated in GB-12 but slightly up-regulated in GB-4, accompanied by generation of variant form of p18 Bax-α in both cell lines. These findings suggest that glutamate toxicity results in cellular death via an apoptotic mechanism which appears to involve the Bcl-2/Bax-α molecular complex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006310815374
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  • 131
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    Targeted Disruption of the bcl-2 Gene in Mice Exacerbates Focal Ischemic Brain Injury (1999)
    Springer
    Metabolic brain disease 14 (1999), S. 117-124 
    Details
    ISSN: 1573-7365
    Keywords: Cerebral ischemia ; focal ischemia ; mutant mice ; bcl-2 ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neuronal death after brain ischemia is mainly due to necrosis but there is also evidence for involvement of apoptosis. To test the importance of apoptosis, we investigated the effect of targeted disruption of the apoptosis-suppressive gene bcl-2 on the severity of ischemic brain injury. Transient focal ischemia for 1 hour was induced by occlusion of the middle cerebral artery in homozygous (n=7) and heterozygous (n = 6) bcl-2 knockout mice as well as in their wildtype littermates (n=5). Bcl-2 ablation did not influence cerebral blood flow but it significantly increased infarct size and neurological deficit score at 1 day after reperfusion in a gene-dose dependent manner. The exacerbation of tissue damage in the absence of Bcl-2 underscores the importance of apoptotic pathways for the manifestation of ischemic injury after transient vascular occlusion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020709814456
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    Analysis of Proliferation and Apoptosis in Brain Gliomas: Prognostic and Clinical Value (1999)
    Springer
    Journal of neuro-oncology 44 (1999), S. 255-266 
    Details
    ISSN: 1573-7373
    Keywords: glioma ; immunohistochemistry ; MIB-1 ; apoptosis ; TUNEL
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract With the introduction of new (immuno-)histochemical techniques it is now possible to assess rates of proliferation and apoptosis in brain gliomas using archival paraffin embedded material. As proliferation and apoptosis are related to tumour growth rate quantification of these processes has prognostic value and is related to tumour grading. In this study we assessed the proliferation rate by measuring the Ki-67 labelling index using the MIB-1 antibody (MIB-LI) and the apoptotic rate using the in situ labelling of DNA strand breaks with TUNEL (TUNEL-LI) in 315 supratentorial gliomas. MIB-LI and TUNEL-LI in astrocytomas (A) where significantly lower compared to anaplastic astrocytomas (AA), glioblastomas (GBM) and oligodendroglial tumours [oligodendrogliomas (O) and anaplastic oligodendrogliomas (AO)]. MIB-LI and TUNEL-LI were significantly lower in AA compared to GBM. In astrocytic tumours MIB-LI and TUNEL-LI appeared to be correlated. As the distinction between A and AA is of clinical value but can be difficult histomorphologically we analysed the prognostic value of MIB-LI and TUNEL-LI in gliomas with particular emphasis on A and AA. MIB-LI below 10% was of prognostic value in A and AA, O and AO but not in GBM on univariate survival analysis. TUNEL-LI was of no prognostic value. With multivariate survival analysis MIB-LI lost prognostic significance in O and AO. Astrocytomas with a gemistocytic component (AG) are similar to A with respect to survival and MIB-LI and TUNEL-LI. MIB-LI is of independent prognostic value in A and AA. Assessment of MIB-LI in A and AA can be used as an aid in distinguishing A and AA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006398613605
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  • 133
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    Protein Kinase C Inhibition by UCN-01 Induces Apoptosis in Human Glioma Cells in a Time-dependent Fashion (1999)
    Springer
    Journal of neuro-oncology 41 (1999), S. 9-20 
    Details
    ISSN: 1573-7373
    Keywords: apoptosis ; astrocytoma ; glioma ; growth inhibition ; protein kinase C ; signal transduction ; UCN-01
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent studies in our laboratory have shown that UCN-01 (7-hydroxystaurosporine), which is a derivative of the non-selective protein kinase inhibitor staurosporine that exhibits relative selectivity for protein kinase C (PKC), is a potent inhibitor of glioma growth in in vitro and in vivo models. This agent exhibits both cytotoxic and cytostatic effects, depending on the time period of drug exposure. In the present study, we examined whether UCN-01-induced cytotoxicity correlated with the induction of apoptosis, and characterized further the time course of this process as a prelude to application of UCN-01 in clinical trials. We first demonstrated that the cytotoxic effects of UCN-01 were associated with the induction of morphological features of apoptosis. Secondly. we identified electrophoretic features of apoptosis semiquantitatively at a series of time points using field inversion gel electrophoresis. These studies showed a peak in the induction of high-molecular-weight DNA fragmentation after 3–6 days of drug treatment. Thirdly, we measured the percentage of cells undergoing apoptosis at various time points using a terminal transferase-catalyzed in situ end-labeling technique, which confirmed a time- and concentration-dependent increase in apoptotic cell numbers. This correlated with a progressive decrease in the percentage of cells that were viable as assessed by trypan blue exclusion. Cell killing peaked within 2–4 days after beginning UCN-01 treatment, but continued at a lower level in the ensuing days. Taken together, these studies demonstrated that extended periods of exposure to UCN-01 are needed for optimal manifestation of cytotoxic effects against glioma cells, a factor that must be taken into consideration in the design of future clinical trials with this agent for malignant gliomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006047025425
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  • 134
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    Spontaneous Regression of a Residual Pineal Tumor after Resection of a Cerebellar Vermian Germinoma (1999)
    Springer
    Journal of neuro-oncology 41 (1999), S. 65-70 
    Details
    ISSN: 1573-7373
    Keywords: germinoma ; spontaneous regression ; multiple intracranial ; germ cell tumor ; immunological mechanism ; apoptosis ; MIB-1 index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A case of multiple intracranial germ cell tumor in which a pineal tumor regressed spontaneously after resection of the cerebellar mass is reported. Immunohistochemical staining of the cerebellar mass showed that most of the infiltrating lymphocytes were positive for CD3 and CD8. The anti-Ki-67 monoclonal antibody MIB-1 staining of the resected tumor revealed a high MIB-1 positivity ratio (36.1%) among the large tumor cells, and TUNEL staining demonstrated that positivity in up to 6% of the tumor cells. Possible mechanisms responsible for this spontaneous regression including immunological responses and apoptosis induced by T lymphocytes are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006155120191
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  • 135
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    Soluble Factors, Including TNFα, Secreted by Human T Cells are Both Cytotoxic and Cytostatic for Medulloblastoma Cells (1999)
    Springer
    Journal of neuro-oncology 43 (1999), S. 115-126 
    Details
    ISSN: 1573-7373
    Keywords: apoptosis ; cell cycle ; cell death ; medulloblastoma ; T cells ; tumour necrosis factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the effect of the treatment of a medulloblastoma cell line by human T cells derived soluble factors. Medulloblastoma is one of the more common aggressive solid neoplasms in children for which there is no adequate therapy. Cell lines established from such tumours may be helpful to test the effect of various molecules on cell proliferation. Previous studies have suggested that T cell-derived factors may be toxic for the medulloblastoma cell line Dev. Cytokines were thought to mediate this effect. In this paper, we described changes in morphology, survival and cell cycle induced in Dev cells cocultured with human T cell lines chronically infected with a retrovirus (HTLV-I) and known to secrete high level of cytokines TNFα, IL1α and IL6. Such cocultures resulted in the death of a part of Dev cells and in decreased proliferation of surviving cells, associated with morphological changes and increase in vimentin expression. Treatment with conditioned medium from infected Dev cells, containing virus induced cytokines, triggered the same effect. Reduction of these effects by TNFα deprivation of conditioned medium suggested that this cytokine may be implicated. Direct treatment of Dev cells with recombinant cytokines indicated that TNFα, but not IL1 or IL6, is associated with Dev cell alterations. TNFα was shown to induce the death of Dev cells by an apoptotic pathway. Furthermore, TNFα had a bimodal effect on the cell cycle of surviving Dev cells. These differential effects of such cytokines on medulloblastoma cells could be therefore of interest for immunotherapy of these tumours.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006273514906
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  • 136
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    Adenovirus-mediated Wild-type p53 Expression Induces Apoptosis and Suppresses Tumorigenesis of Experimental Intracranial Human Malignant Glioma (1999)
    Springer
    Journal of neuro-oncology 43 (1999), S. 99-108 
    Details
    ISSN: 1573-7373
    Keywords: adenoviral gene transfer ; p53 ; apoptosis ; experimental malignant gliomas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adenoviral-mediated gene transfer for the treatment of experimental intrinsic malignant brain neoplasms holds promise. The role, however, of intracellular, adenoviral-mediated p53 expression to inhibit growth of experimental human intracranial malignant gliomas remains largely unexplored. Using the AdCMV.p53 vector we measured the in vitro expression of p53 and the resultant effect upon U251 human malignant glioma cellular proliferation. We further measured the survival of nude mice after intracranial injection of the infected vs. control U251 cells. The growth of the infected U251 cells was inhibited when compared to both the uninfected cells and cells infected with the control vector (AdCMV.Null). Agarose gel electrophoresis confirmed the AdCMV.p53-dependent cellular apoptosis. Nude mice having intracranial injections of the U251 cells infected with the control (AdCMV.Null) vector showed diminished survival. In contrast, mice having intracranial injections of the cells infected with the AdCMV.p53 vector showed 100% survivorship measured 100 days after treatment. Gene therapy via the AdCMV.p53 viral vector holds promise for the clinical treatment of human malignant gliomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006289505801
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  • 137
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    Neuroblastoma as a Neurobiological Disease (1999)
    Springer
    Journal of neuro-oncology 41 (1999), S. 159-166 
    Details
    ISSN: 1573-7373
    Keywords: neuroblastoma ; chemotherapy ; apoptosis ; dopamine receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract While neuroscientists are often involved in the assessment and care of patients with central nervous system tumors, they are only rarely involved in the case of peripheral nervous system neoplasia. Neuroblastoma is a childhood tumor of the primitive sympathetic nervous system. It is at once one of the most common and one of the most deadly tumors of childhood. The prognosis for children with this tumor has not changed in the past two decades. Clearly, a fresh approach to neuroblastoma is needed. The neuroscientist has much to add to our understanding and treatment of neuroblastoma and its sequelae. Conversely, neuroblastoma has much to teach us regarding the normal development of the neural crest and the aberrant loss of neurons in this lineage. A neuroscientist's approach to neuroblastoma, its biology and clinical features, is presented herein.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006171406740
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  • 138
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    Lovastatin-induced Apoptosis of Human Medulloblastoma Cell Lines in vitro (1999)
    Springer
    Journal of neuro-oncology 42 (1999), S. 1-11 
    Details
    ISSN: 1573-7373
    Keywords: apoptosis ; chemotherapy ; human cell lines ; lovastatin ; medulloblastoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Medulloblastoma is a malignant paediatric central nervous system tumor with a poor prognosis, stimulating the evaluation of improved treatment strategies. Lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, is currently used to treat patients with hypercholesterolemia. This compound also inhibits the production of non-steroidal mevalonate derivatives that are implicated in the control of cellular proliferation, and can induce cell-cycle arrest in vitro. We recently showed that lovastatin inhibited growth and promoted apoptosis of neuroblastoma, the peripheral nervous system ‘cousin’ of medulloblastoma. Therefore the potential of lovastatin as a possible anticancer drug against medulloblastoma was evaluated in vitro. Four medulloblastoma cell lines, Daoy, UW228, D341 Med and D283 Med, were treated with 1–40 µM of lovastatin in vitro. Analysis of cell morphologic changes, cell viability, DNA fragmentation and flow cytometry in all four cell lines showed growth inhibition and induction of apoptosis with lovastatin treatment. As little as 10 µM of lovastatin was sufficient to cause a marked reduction in cell numbers, and more than 20 µM of lovastatin induced 〉90% cells to undergo apoptosis, after intervals ranging between 36 and 96 h, depending on the cell line. Lovastatin induced apoptosis in these cell lines was concomitant with cell cycle arrest in G1. The attached cell lines UW228 and Daoy were more sensitive to lovastatin than D283 Med and D341 Med. Daoy cells which survived several cycles of lovastatin treatment could still be induced to undergo apoptosis after longer treatment times. The efficient induction of apoptosis by lovastatin favours this drug as a potential new avenue of therapeutic intervention for medulloablastoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006164406202
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  • 139
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    Glucocorticoid Treatment of Primary CNS Lymphoma (1999)
    Springer
    Journal of neuro-oncology 43 (1999), S. 237-239 
    Details
    ISSN: 1573-7373
    Keywords: primary CNS lymphoma ; glucocorticoids ; cerebral edema ; apoptosis ; bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Glucocorticoid therapy may result in the rapid resolution of cerebral mass lesions in patients with primary CNS lymphoma. Since glucocorticoids will obscure the histological diagnosis of primary CNS lymphoma upon biopsy, steroids should be withheld if primary CNS lymphoma is a likely diagnosis by neuroradiological criteria. The lympholytic effect of glucocorticoids is mediated by cytoplasmic steroid receptors which are translocated to the nucleus and signal apoptosis. Glucocorticoid-induced apoptosis of lymphoid cells does not require wild-type p53 activity, seems not to depend on caspase activation, but is attenuated by the bcl-2 protooncogene product. Long-term glucocorticoid therapy of primary CNS lymphoma is not recommended because relapse is probably inevitable and because of the prominent side effects of long-term glucocorticoid treatment. Further, long-term glucocorticoid treatment is contraindicated in immunocompromised patients with primary CNS lymphoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006254518848
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  • 140
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    Cellular uptake of the prion protein fragment PrP106-126 in vitro (1999)
    Springer
    Journal of neurocytology 28 (1999), S. 149-159 
    Details
    ISSN: 1573-7381
    Keywords: prion disease ; transmissible spongiform encephalopathy ; cell culture ; toxicity ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aetiological agent of prion disease is proposed to be an aberrant isoform of the cell surface glycoprotein known as the prion protein (PrPc). This pathological isoform (PrPSc) is abnormally deposited in the extracellular space of diseased CNS. Neurodegeneration in these disease has been shown to be associated with accumulation of PrPSc in affected tissue. To investigate the possible uptake mechanisms that may be required for PrPSc-induced neurodegeneration we studied the cellular trafficking of the neurotoxic fragment, PrP106-126. We were able to detect, by fluorescence microscopy, PrP106-126 inclusions in murine neurones, astrocytes and microglia in vitro. These inclusions were abundant after 24 hour exposure and still present 48h post-exposure. Shorter exposure times yielded only occasional cells with inclusions. Large extracellular aggregates of PrP106-126 could also be detected, which appeared in a time dependent manner. The appearance of inclusions or aggregates was not dependent on PrPc expression as determined by exposure of peptides from PrP-null mice. Using transmission electron microscopy and gold particle detection, positively labelled osmiophilic inclusions of peptide could be detected in the cytoplasm of exposed cells. These results demonstrate that cultured cells are capable of sequestering PrP106-126 and may indicate uptake pathways for PrPSc in various cell types. Toxicity of PrP106-126 may thus be mediated via a sequestration pathway that is not effective for this peptide in PrP-null cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007028323666
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  • 141
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    Verotoxin/Globotriaosyl Ceramide Recognition: Angiopathy, Angiogenesis and Antineoplasia (1999)
    Springer
    Bioscience reports 19 (1999), S. 345-354 
    Details
    ISSN: 1573-4935
    Keywords: Glycolipid ; apoptosis ; intracellular traffic ; multidrug resistance ; ovarian carcinoma ; astrocytoma ; post transplant lymphoproliferative disease ; bone marrow purging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Verotoxin (VT) is involved in the etiology of both hemorrhagic colitis and the hemolytic uremic syndrome which are microvasculopathies of the colon and pediatric renal glomerulus respectively. Thus, VT can be considered a vasotoxin. Cell sensitivity in vitro varies according to the receptor glycolipid (globotriaosyl ceramide-Gb3) expression and also to intracellular trafficking of the receptor/toxin complex, such that in highly sensitive cells, the toxin is targeted to the endoplasmic reticulum and nuclear envelope. Such cells include tumor cells which have become drug resistant. Thus Gb3 is upregulated in certain tumors and when such tumor cells become drug resistant, their sensitivity to verotoxin increases. This may be due to a direct role of the MDR1 drug efflux pump in glycolipid biosynthesis. In addition to the tumor tissue, the toxin receptor may also be expressed in the tumor neovasculature suggesting that activated endothelial cells may be verotoxin sensitive. Thus VT may have both a direct and indirect antineoplastic potential. VT has proved highly effective in a xenograft cancer model and the possible therapeutic use of VT is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020299819637
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  • 142
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    Ceramide Glycanase Activities in Human Cancer Cells (1999)
    Springer
    Bioscience reports 19 (1999), S. 449-460 
    Details
    ISSN: 1573-4935
    Keywords: ceramide glycanase ; cancer cells ; glycosphingolipid ; sphingosine ; ceramide ; apoptosis ; PPMP ; PDMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Ceramide glycanase (CGase) activities have been detected in different human tumor cells (colon, carcinoma Colo-205; neuroblastoma, IMR-32; breast cancer lines, SKBr3 and MCF7). However, the level of enzymatic activity is lower in these cells compared to that present in other mammalian tissues reported before (Basu, M., Kelly, P., Girzadas, M. A., Li, Z., and Basu, S. Methods Enzymol. (in press)). The majority of CGase activity was found in the 100,000g soluble supernatant fraction isolated from all these cell lines and tissues. Using the soluble enzyme, the requirement for optimum CGase activity was found to be consistent with previous observations found for rat and rabbit tissues (Basu, M., Dastgheib, S., Girzadas, M. A., O'Donnell, P. H., Westervelt, C. W., Li, Z., Inokuchi, J. I., and Basu, S. (1998) Acta Pol. Biochim. 42:327). The CGase activities from both Colo-205 and IMR-32 cells are optimum at a protein to detergent ratio of one. All the mammalian CGases, including human cancer cells, show an optimum pH between 5.5 and 5.8 in sodium acetate buffer. The CGase activities from cancer cells are found to be cation-independent; however, mercury, zinc, and copper ions seem to inhibit the enzyme activity substantially in both tumor cells lines. The mercury ion inhibition of CGase activities from all different sources indicates a possible structural homology in the CGase proteins. Radiolabeled substrates, labeled at the sphingosine double bond or at the 3-position of sphingosine without modifying double bond of sphingosine were used in this investigation. Both were active substrates with all enzyme preparations isolated from different cancer cells (apparent Km, 500 μM for nLcOse5[3H-DT]Cer and 350 μM for GgOse4[sph-3-3H]Cer with Colo-205 enzyme). Structural analogues of ceramide and sphingosine (L-PPMP, L-PDMP, alkylamines, and Tamoxifen) inhibited cancer cell CGase activities in vitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020220524180
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  • 143
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    Immunocytochemical Accumulation of p53 in Corticotroph Adenomas: Relationship with Heat Shock Proteins and Apoptosis (1999)
    Springer
    Pituitary 1 (1999), S. 207-212 
    Details
    ISSN: 1573-7403
    Keywords: apoptosis ; corticotroph adenomas ; heat shock proteins ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pathogenesis of corticotroph adenomas is unknown. In a recent study accumulation of p53 protein was detected by immunohistochemistry in a substantial proportion of pituitary corticotroph adenomas, and it has been suggested that it may be causally related to their development. However, other immunohistochemical studies have not confirmed the high incidence of p53 accumulation in this tumor type. Therefore, in the present study, p53 protein accumulation was re-examined in a series of 31 cases of corticotroph adenomas, using different sets of well validated anti-p53 antibodies. Furthermore, in view of the known association of p53 protein with apoptosis, and the known property of p53 to form complexes with heat shock proteins (HSPs), the relationship of p53 accumulation in corticotroph adenomas with apoptosis and HSP-70 was also investigated. Tumor samples staining positively for ACTH from patients with Cushing's disease or Nelson's syndrome were studied. Accumulation of p53 protein was tested by the standard ABC method using two different sets of clone Pab1801 and DO-7 monoclonal antibodies, applied after incubation of sections in a microwave oven. Using the DO-7 antibody, nuclear accumulation of p53 protein was detected in a total of 15 cases, with cytoplasmic staining observed in only 3 tumors. In contrast, using the Pab1801 antibody nuclear staining was observed in only 5 adenomas, with 11 adenomas demonstrating focal cytoplasmic immunoreactivity. Parallel sections of all corticotroph tumors demonstrating cytoplasmic accumulation of p53 protein were tested for the immunohistochemical presence of heat shock protein HSP-70. A striking similar distribution pattern of these two proteins was observed. Apoptosis, identified by the in situ end labeling technique, was detected in a total of 15 out of 28 corticotroph adenomas tested. Calculation of the apoptotic labeling index (ALI) by image analysis showed a significantly lower ALI in those corticotroph adenomas demonstrating nuclear p53 accumulation compared to those with no nuclear p53 immunostaining (p〈0.05). There was no significant difference in the ALI between cytoplasmic p53 positive and negative tumors. It is concluded that depending on the antibody used there is a significant variation of p53 protein detection in corticotroph adenomas. Overall, a significant proportion of corticotroph adenomas studied expressed the p53 protein, which depending on the antibody used, was located either in the nucleus and/or the cytoplasm of tumorous corticotroph cells. Cytoplasmic accumulation of p53, as shown by our colocalization studies with HSP-70, may be due to p53/HSP-70 complex formation. Although such a complex-mediated cytoplasmic exclusion of p53 has no significant effect on apoptosis, nuclear accumulation of p53 protein is associated with a significantly lower apoptotic index indicating a failure of p53 protein to exert its apoptotic action in at least a subset of this tumor type.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009929704018
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  • 144
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    Adenosine-induced cell death: evidence for receptor-mediated signalling (1999)
    Springer
    Apoptosis 4 (1999), S. 197-211 
    Details
    ISSN: 1573-675X
    Keywords: Adenosine ; apoptosis ; necrosis ; physiopathological implications.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Adenosine modulates the proliferation, survival and apoptosis of many different cell types, ranging from epithelial, endothelial and smooth muscle cells, to cells of the immune and neural lineages. In this review, we critically discuss the available in vitro and in vivo data which support a role for adenosine in both development-associated apoptosis, and in diseases characterized by either pathologically increased cell death (e.g., ischemia, trauma and aging-associated neurodegeneration) or abnormally reduced spontaneous apoptosis (e.g., cancer). Particular emphasis is given to the possible role of extracellular adenosine receptors, since these may represent novel and attractive molecular targets for the pharmacological modulation of apoptosis. In some instances, adenosine-induced cell death has been demonstrated to require entry of the nucleoside inside cells; however, in many other cases, activation of specific adenosine extracellular receptors has been demonstrated. Of the four G protein-coupled adenosine receptors so far identified, the A2A and the A3 receptors have been specifically implicated in modulation of cell death. For the A3 receptor, results obtained by exposing both cardiomyocytes and brain astrocytes to graded concentrations of selective agonists suggest induction of both cell protection and cell death. Such opposite effects, which likely depend on the degree of receptor activation, may have important therapeutic implications in the pharmacological modulation of cardiac and brain ischemia. For the A2A receptor, recent intriguing data suggest a specific role in immune cell death and immunosuppression, which may be relevant to both adenosine-deaminase-immunodeficiency syndrome (a pathology characterized by accumulation of adenosine to toxic levels) and in tumors where induction of apoptosis via activation of specific extracellular receptors may be desirable. Finally, preliminary data suggest that, in a similar way to the adenosine-deaminase-immunodeficiency syndrome, the abnormal accumulation of adenosine in degenerative muscular diseases may contribute to muscle cell death. Although the role of adenosine receptors in this effect still remains to be determined, these data suggest that adenosine-induced apoptosis may also represent a novel pathogenic pathway in muscular dystrophies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009666707307
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  • 145
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    Apoptin®-induced apoptosis: a review (1999)
    Springer
    Apoptosis 4 (1999), S. 317-319 
    Details
    ISSN: 1573-675X
    Keywords: Anti-tumor therapy ; Apoptin® ; apoptosis ; Bcl-2 ; p53.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Apoptin, a protein encoded by an avian virus, induces apoptosis in various cultured human tumorigenic and/ or transformed cell lines, e.g. derived from breast and lung tumor, leukemia, lymphoma, osteosarcoma melanoma, cholangiocarcinoma, and hepatoma. In such cells, Apoptin induces p53-independent apoptosis, and the proto-oncogene Bcl-2 can accelerate this effect. The latter is surprising for, in general, Bcl-2 is known to inhibit e.g., p53-induced apoptosis. On the other hand, in normal non-transformed human cells, Apoptin is unable to induce apoptosis, even when Bcl-2 is over-expressed. In animal models Apoptin-induced apoptosis appears to be a safe and efficient anti-tumor agent. These data, in continuation with the observations that Apoptin is specifically stimulated by Bcl-2 in tumor cells, does not need p53, and is not inhibited by Bcr-Abl in these cells, imply that Apoptin is a potential anti-tumor therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009687019221
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  • 146
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    Apoptosis in ventricular myocytes: the role of tumor suppressor proteins (1999)
    Springer
    Apoptosis 4 (1999), S. 229-234 
    Details
    ISSN: 1573-675X
    Keywords: Adenovirus ; apoptosis ; Bcl-2 ; p53 ; Rb ; ventricular myocytes.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Apoptosis or programmed cell death is an important physiologic event crucial for the selective removal of damaged or unwanted cells from body tissues. In the cardiovascular system, apoptosis has been observed in the vasculature and myocardium. Untimely or inappropriate myocardial cell loss through an apoptotic process may contribute to ventricular remodeling and the ultimate demise of ventricular function following injury. Therapeutic interventions designed to modulate or prevent myocardial apoptotic cell loss may therefore prove beneficial in maintaining cardiac function. Incite into the molecular mechanisms that govern apoptosis in mammalian cells has led to the identification of several key factors that promote or prevent the apoptotic process. In this report, we discuss putative regulators of cardiac cell apoptosis with specific reference to the tumor suppressor proteins, p53 and Rb. The interplay between these factors, as well as the anti-apoptotic molecules related to the Bcl-2 the family are discussed in the context of the heart under normal and disease conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009640124029
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  • 147
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    Tau protein is involved in the apoptotic process induced by anti-microtubule agents on neuroblastoma cells (1999)
    Springer
    Apoptosis 4 (1999), S. 47-58 
    Details
    ISSN: 1573-675X
    Keywords: Anti-microtubule agents ; apoptosis ; doxorubicin ; neuroblastoma ; tau ; taxoid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Paclitaxel and docetaxel are potent anti-microtubule and antimitotic agents that induce apoptosis in bone marrow-derived cells and epithelial cells. This study examined apoptosis induced by anti-microtubule agents in the neuroblastoma SK-N-SH cell line with a special focus on tau protein which is one of the main Microtubule-Associated- Proteins (MAPs) in neuronal cells. In time, treatment with 1 μM paclitaxel successively induced formation of bundles, then pseudo-asters concomitantly with mitotic block and phosphorylation of bcl-2 (48 h), then phosphorylation of tau and externalization of phosphatidylserine at the early phase of apoptosis (72 h) and finally DNA fragmentation (96 h). Similar results were obtained with 0.5 μM vinorelbine. Paclitaxel induced a lower increase in tau phosphorylation in differentiated SK-N-SH/RA+ cells which are less sensitive to apoptosis. Moreover, doxorubicin whose mechanism of action is independent of microtubules also induced immunostaining of tau at 72 h treatment. In conclusion, our results on neuroblastoma cells show that overexpression of hyperphosphorylated tau is involved in the apoptotic process induced by anti-microtubule agents and may be extended to others cytostatic drugs. Thus, tau protein may play a role in the cellular events observed in neuroblastoma cells undergoing apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009682116158
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  • 148
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    IL-3 induces apoptosis in a ras-transformed myeloid cell line (1999)
    Springer
    Apoptosis 4 (1999), S. 71-80 
    Details
    ISSN: 1573-675X
    Keywords: abl ; apoptosis ; interleukin-3 ; oncogenes ; ras.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Growth factors promote cell survival and proliferation. Homeostasis is maintained by programmed cell death which occurs when the growth stimulus is withdrawn, in response to negative growth regulators such as interferons, TNF-α and CD95 ligand, or following differentiation. Although acutely-transforming oncogenes often overcome the need for growth factors, growth regulatory cytokines can influence proliferative responses of transformed cells. In this study we investigated the effects of IL-3 on the proliferative responses of parental bone marrow-derived 32D cells and cells transformed with ras and abl oncogenes. We show that treatment of ras-transformed 32D cells with IL-3 reduced proliferative responses and decreased colony-forming ability. These effects were exacerbated in the absence of serum and associated with inhibition of tyrosine kinase activity, down-regulation of RAS and MYC expression, and induction of apoptosis as indicated by DNA fragmentation. In contrast, treatment of parental 32D cells with IL-3, which is obligatory for cell survival and proliferation, increased tyrosine kinase activity, upregulated MYC and RAS expression and maintained DNA integrity. With abl-transformed cells, proliferation and colony-forming ability were also inhibited by IL-3. Tyrosine kinase activity and MYC expression were reduced, but early apoptosis was not evident. Calcium uptake however, was stimulated by IL-3 in both parental and oncogene-transformed cells. These results suggest that threshold levels of tyrosine kinase activity are necessary for cell survival and proliferation and that with ras-transformed cells, IL-3 treatment may result in this threshold being breached. We conclude that in some situations, growth-promoting cytokines can inhibit proliferation of transformed cells and induce cell death by apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009686220607
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  • 149
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    Ameloblast apoptosis and IGF-1 receptor expression in the continuously erupting rat incisor model (1999)
    Springer
    Apoptosis 4 (1999), S. 441-447 
    Details
    ISSN: 1573-675X
    Keywords: ameloblasts ; amelogenesis ; apoptosis ; insulin-like growth factor.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Enamel-producing cells (ameloblasts) pass through several phenotypic and functional stages during enamel formation. In the transition between secretory and maturation stages, about one quarter of the ameloblasts suddenly undergo apoptosis. We have studied this phenomenon using the continuously erupting rat incisor model. A special feature of this model is that all stages of ameloblast differentiation are presented within a single longitudinal section of the developing tooth. This permits investigation of the temporal sequence of gene and growth factor receptor expression during ameloblast differentiation and apoptosis. We describe the light and electron microscopic morphology of ameloblast apoptosis and the pattern of insulin-like growth factor-1 receptor expression by ameloblasts in the continuously erupting rat incisor model. In the developing rat incisor, ameloblast apoptosis is associated with downregulated expression of the insulin-like growth factor-1 receptor. These data are consistent with the hypothesis that ameloblasts are “hard wired” for apoptosis and that insulin-like growth factor-1 receptor expression is required to block the default apoptotic pathway. Possible mechanisms of insulin-like growth factor-1 inhibition of ameloblast apoptosis are presented. The rat incisor model may be useful in studies of physiological apoptosis as it presents apoptosis in a predictable pattern in adult tissues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009600409421
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  • 150
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    Apoptotic cell death and related gene expression in metastatic tumors of AKR lymphomas of varying malignancy (1999)
    Springer
    Apoptosis 4 (1999), S. 429-440 
    Details
    ISSN: 1573-675X
    Keywords: AKR lymphoma malignancy variants ; apoptosis ; apoptosis-related gene expression ; tumor progression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Resistance to apoptosis may be related to tumor progression, due to the implications it might have on both tumor mass and genetic instability. We compared the tendency to spontaneous apoptosis and the proliferative capacity of metastatic growths of several AKR lymphoma variants (TAU-45, TAU-47, TAU-44, TAU-33, TAU-42 and TAU-46, in the order of increasing metastatic potential). We further compared the expression of several apoptosis-related genes. Cell proliferative capacity did not appear to determine malignant behavior since, on the whole, a decrease in S + G2M fraction was observed with increasing malignancy. Sensitivity to apoptotic cell death decreased with increasing malignancy when comparing the TAU-45, TAU-47, TAU-44 and TAU-33 variants, suggesting a role of reduced apoptosis in this T-cell lymphoma. An increase in Bcl-2 content with increasing aggressiveness among these variants, implicates this protein in this tumor progression-related resistance to apoptosis. However, the two variants of highest malignancy, TAU-42 and TAU-46, did not follow the same trend, since they displayed a relatively high content in apoptotic cells and a low Bcl-2 content. Fas receptor expression did not correlate with tendency to apoptosis, indicating that malignant behavior in the AKR lymphoma does not depend on CD95/Fas/APO1 downregulation. Overexpression of p53 was observed only in one of the variants of lowest malignancy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009648325350
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  • 151
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    Signalling steps in apoptosis by ether lipids (1999)
    Springer
    Apoptosis 4 (1999), S. 419-427 
    Details
    ISSN: 1573-675X
    Keywords: Anti-oxidant defence ; apoptosis ; ether lipids ; glutathione ; ionising radiation ; stress.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We have investigated the mechanisms of induction of apoptosis by the antineoplastic ether lipid ET-18-OCH3 (ALP) in sensitive S49wt mouse lymphoma cells and ALP-resistant S49ar variants, both with wild-type p53, and in related L1210 cells with mutated p53. Ether lipid-resistant S49ar cells were cross-resistant to extracellular stress factors (cold shock, heat shock, H2O2, dimethylsulfoxide) and to radiation-induced apoptosis but not to physiological apoptotic signals (dexamethasone, growth factor deprivation, thapsigargin, C2-ceramide) and expressed similar levels of the apoptosis-regulating proteins Bcl-2, Bcl-X, Bax, Bad and Bak as did the parent S49wt cells. The uptake of [3H]-ALP was strongly reduced in the stress-resistant cells but this was not associated with significant differences in membrane cholesterol:phospholipid content nor in membrane microviscosity. In S49ar cells the activity of the antioxidant enzyme glutathione peroxidase (GSH-Px) was increased 4-fold and depletion of glutathione with the drug L-buthionine-S-R-sulfoximine (L-BSO) lowered the resistance of S49ar cells to ALP, stress factors and ionising radiation. The results indicate that ether lipids induce apoptosis by imposing a special form of physico-chemical stress, mediated by reactive oxygen species but independent of p53 status. The capacity of glutathione-dependent anti-oxidant defence appeared an important and shared determinant of the sensitivity to ether lipids, several types of extracellular stress and ionising radiation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009644208512
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  • 152
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    Sequential occurrence of mitochondrial and plasma membrane alterations, fluctuations in cellular Ca2+ and pH during initial and later phases of cell death (1999)
    Springer
    Apoptosis 4 (1999), S. 455-460 
    Details
    ISSN: 1573-675X
    Keywords: Annexin V ; apoptosis ; flow cytometry ; intracellular Ca2+ ; intracellular pH ; mitochondrial membrane potential.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The sequential occurrence of plasma and mitochondrial membrane alterations, intra-cellular pH shifts and changes in intracellular Ca2+ concentration after induction of cell death was monitored by flow cytometry in Jurkat and HSB2-cells. Cell death was induced by treatment with anti-Fas antibodies or by irradiation. Phosphatidylserine (PS) exposure and plasma membrane integrity were measured with FITC-Annexin V adhesion and by Propidium Iodide exclusion. Transition of the mitochondrial membrane potential was monitored by the occurrence of decay of DiOC6 fluorescence. Intracellular pH shifts were monitored by changes in the ratio of fluorescence at 575 nm and at 635 nm of SNARF-1-AM. Fluctuations in intracellular Ca2+ concentration were established by changes in Fura red quenching. The Jurkat cells were sensitive to anti-Fas treatment, while HSB-2 cells were not. HSB-2 cells appeared more sensitive to radiation damage than Jurkat cells. In all experiments the transition of mitochondrial membrane potential occurred first, almost immediately followed by PS exposure. Fluctuations in intracellular Ca2+ concentration occurred later and were less outspoken. A decrease in intracellular pH occurred not earlier than 24 hours after anti-Fas treatment. Chelation of intracellular Ca2+ concentration with BAPTA-AM had no effect on the time sequence of cell death related events.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009604510329
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  • 153
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    Pharmacodynamics and Toxicodynamics of Drug Action: Signaling in Cell Survival and Cell Death (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 790-798 
    Details
    ISSN: 1573-904X
    Keywords: MAPK ; caspases ; chemopreventive agents ; phase II drug metabolizing enzymes ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract In therapeutic response to drugs, the plasma concentration range leads to the establishment of a safe and effective dosage regimen. Our hypothesis is that by studying drug concentration-dependent effect on signal transduction mechanisms, a better understanding of the beneficial pharmacodynamic and adverse toxicodynamic responses elicited by the drug may be achieved. Using two classes of chemopreventive compounds (phenolic antioxidants and isothiocyanates), we illustrate the potential utility of two signal transduction pathways elicited by these agents to predict the pharmacodynamic effect (induction of Phase II drug metabolizing enzymes) and the potential toxicodynamic response (stimulation of caspase activity and cytotoxic cell death). At lower concentration, phenolic antioxidants and isothiocyanates activate mitogen-activated protein kinase (MAPK; extracellular signal-regulated protein kinase 2, ERK2; and c-Jun N-terminal kinase 1, JNK1) in a concentration-and time-dependent manner. The activation of MAPK by these compounds may lead to the induction of cell survival/protection genes such as c-jun, c-fos, or Phase II drug metabolizing enzymes. However, at higher concentrations, these agents activate another signaling molecule, ICE/Ced3 cysteine protease enzymes (caspases) leading to apoptotic cell death. The activation of these pathways may dictate the fate of the cells/tissues upon exposure to drugs or chemicals. At lower concentrations, these compounds activate MAPK leading to the induction of Phase II genes, which may protect the cells/tissues against toxic insults and therefore may enhance cell survival. On the other hand, at higher concentrations, these agents may activate the caspases, which may lead to apoptotic cell death, and have toxicity. Understanding the activation of these and other signal transduction events elicited by various drugs and chemicals may yield insights into the regulation of gene expression of drug metabolizing enzymes and cytotoxicity. Thus, the study of signaling events in cell survival (hemeostasis) and cell death (cytotoxicity) may have practical application during pharmaceutical drug development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1011953431486
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  • 154
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    Effect of ethrel on apoptosis in carrot protoplasts (1999)
    Springer
    Plant growth regulation 27 (1999), S. 119-123 
    Details
    ISSN: 1573-5087
    Keywords: apoptosis ; carrot protoplast ; DNA ladder ; ethrel ; ethylene ; nucleus condensation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract In recent years, apoptosis has been reported to exist in plants during normal development and in response to stress. However, little is known about the relation of hormones to this form of programmed cell death. Here, we report examination of characteristics of apoptosis in carrot protoplasts induced by ethylene evolved from ethrel (2-chloroethylphosphonic acid). Nucleus condensation and DNA ladders were observed, and neutral comet assay, which detects DNA cleavage, also provided evidence that ethrel treatment resulted in nuclear DNA fragmentation. Strikingly, a close correlation between the incidence of DNA comets and the percentage of apoptotic protoplasts was shown in ethrel-treated carrot protoplasts. In conclusion, this study demonstrated that ethylene is an active inducer of apoptosis in carrot protoplasts, and that ethylene-induced plant cell death showed characteristics similar to those of apoptosis in animals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006105101813
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  • 155
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    Gangliosides Attenuate Ethanol-Induced Apoptosis in Rat Cerebellar Granule Neurons (1999)
    Springer
    Neurochemical research 24 (1999), S. 1107-1115 
    Details
    ISSN: 1573-6903
    Keywords: Ethanol ; apoptosis ; gangliosides ; LIGA20 ; cerebellar granule cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ethanol significantly enhances cell death of differentiated rat cerebellar granule neurons on culture in a serum-free medium containing a depolarizing concentration of KCl (25 mM), 5 μM MK-801 (an NMDA receptor antagonist), and 20–200 mM ethanol for 1–4 days. Cell death augmented by ethanol was concentration- and time-dependent with neurons displaying hallmark apoptotic morphology and DNA fragmentation that correlated with the activation of cytosolic caspase-3. Inclusion of 5 μM MK-801 or 100 μM glycine in culture media did not alter rates of cell death indicating ethanol toxicity is mediated via an NMDA receptor-independent pathway. Preincubation with 50 μM gangliosides GM1, GD1a, GD1b or GT1b for 2 h, or preincubation with 10 μM LIGA20 (a semisynthetic GM1 with N-dichloroacetylsphingosine) for 10 min, attenuated caspase-3 activity and ethanol-induced cell death. Data show native gangliosides and a synthetic derivative are potently neuroprotective in this model of ethanol toxicity, and potentially serve as useful probes to further unravel the mechanisms relevant to neuronal apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020704218574
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  • 156
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    Mitochondrial Events in the Life and Death of Animal Cells: A Brief Overview (1999)
    Springer
    Journal of bioenergetics and biomembranes 31 (1999), S. 291-304 
    Details
    ISSN: 1573-6881
    Keywords: Cell death ; aging ; necrosis ; apoptosis ; mitochondria ; oxidative phosphorylation ; electron transport chain ; ATP synthase ; cytochrome c ; mitochondrial DNA ; reactive oxygen species (ROS)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract Traditionally, mitochondria have been viewed as the “powerhouse” of the cell, i.e., the site of theoxidative phosphorylation machinery involved in ATP production. Consequently, much of theresearch conducted on mitochondria over the past 4 decades has focused on elucidating both thosemolecular events involved in ATP synthesis by oxidative phosphorylation and those involved inthe biogenesis of the oxidative phosphorylation machinery. While monumental achievements havebeen made, and continue to be made, in the study of these remarkable but extremely complexprocesses essential for the life of most animal cells, it has been only in recent years that a largebody of biological and biomedical scientists have come to recognize that mitochondria participatein other important processes. Two of these are cell death and aging which, not surprisingly, are relatedprocesses both involving, in part, the oxidative phosphorylation machinery. This new awareness hassparked a new and growing area of mitochondrial research, that has become of great interest to awide variety of scientists ranging from those involved in elucidating the role of mitochondria incell death and aging to those interested in either suppressing or facilitating these processes as itrelates to identifying new therapies or drugs for human disease. It is the purpose of this briefintroductory review to provide an overview of those mitochondrial events involved in the life anddeath of animal cells and to indicate how these events might relate to the human aging process.Much more is known, much remains controversial, and even more remains to be learned as indicatedin the excellent set of minireviews that follow.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005453700533
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  • 157
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    Mitochondria at the Crossroad of Apoptotic Cell Death (1999)
    Springer
    Journal of bioenergetics and biomembranes 31 (1999), S. 321-326 
    Details
    ISSN: 1573-6881
    Keywords: Mitochondria ; apoptosis ; caspases ; cytochrome c ; Fas ; bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract In the past few years, it has become widely appreciated that apoptotic cell death generallyinvolves activation of a family of proteases, the caspases, which undermine the integrity ofthe cell by cleavage of critical intracellular substrates. Caspases, which are synthesized asinactive zymogens, are themselves caspase substrates and this cleavage leads to their activation.Hence, the potential exists for cascades of caspases leading to cell death. However, it has beenrecently recognized that another, perhaps more prominent route to caspase activation, involvesthe mitochondria. Upon receipt of apoptotic stimuli, either externally or internally generated,cells initiate signaling pathways which converge upon the mitochondria to promote release ofcytochrome C to the cytoplasm; cytochrome c, thus released, acts as a potent cofactor incaspase activation. Even cell surface “death receptors” such as Fas, which can trigger directcaspase activation (and potentially a caspase cascade), appear to utilize mitochondria as partof an amplification mechanism; it has been recently demonstrated that activated caspases cancleave key substrates to trigger mitochondrial release of cytochrome c, thereby inducing furthercaspase activation and amplifying the apoptotic signal. Therefore, mitochondria play a centralrole in apoptotic cell death, serving as a repository for cytochrome c.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005471701441
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  • 158
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    Mitochondrial Uncoupling: Role of Uncoupling Protein Anion Carriers and Relationship to Thermogenesis and Weight Control “The Benefits of Losing Control” (1999)
    Springer
    Journal of bioenergetics and biomembranes 31 (1999), S. 493-506 
    Details
    ISSN: 1573-6881
    Keywords: Energy expenditure ; reactive oxygen species ; cellular viability ; apoptosis ; necrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract Uncoupling proteins, a subgroup of the mitochondrial anion transporter superfamily, have beenidentified in prokaryotes, plants, and mammalian cells. Evolutionary conservation of thesemolecules reflects their importance as regulators of two critical mitochondrial functions, i.e.,ATP synthesis and the production of reactive oxygen species (ROS). Although the amino acidsequences of the three mammalian uncoupling proteins, UCP1, UCP2 and UCP3, are verysimilar, each homolog is the product of a unique gene and important differences have beendemonstrated in their tissue-specific expression and regulation. UCP1 and UCP3 appear to bekey regulators of energy expenditure, and hence, nonshivering thermogenesis, either in brownadipose tissue (UCP1) or skeletal muscle (UCP3). UCP2 is expressed more ubiquitously,although generally at low levels, in many tissues. There is conflicting evidence about itsimportance as a regulator of resting metabolic rate. However, evidence suggests that thishomolog might modulate the mitochondrial generation of ROS in some cell types, includingmacrophages and hepatocytes. While the induction of various uncoupling protein homologsprovides adaptive advantages, both to the organism (e.g., thermogenesis) and to individual cells(e.g., reduced ROS), increased uncoupling protein activity also increases cellular vulnerability tonecrosis by compromising the mitochondrial membrane potential. This narrow “risk—benefit”margin necessitates tight control of uncoupling protein activity in order to preserve cellularviability and much remains to be learned about the regulatory mechanisms involved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005452624640
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  • 159
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    Hepatotoxicity due to mitochondrial dysfunction (1999)
    Springer
    Cell biology and toxicology 15 (1999), S. 367-373 
    Details
    ISSN: 1573-6822
    Keywords: apoptosis ; drugs ; hepatitis ; mitochondria ; steatosis ; steatohepatitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Mitochondria are involved in fatty acid β-oxidation, the tricarboxylic acid cycle, and oxidative phosphorylation, which provide most of the cell energy. Mitochondria are also the main source of reactive oxygen species in the cell and are involved in cell demise through opening of the mitochondrial permeability transition pore. It was therefore to be expected that mitochondrial dysfunction could be a major mechanism of drug-induced liver disease. Microvesicular steatosis (which may cause liver failure, coma, and death) is the consequence of severe impairment of mitochondrial β-oxidation. Endogenous compounds (such as cytokines or female sex hormones) or xenobiotics (including toxins such as ethanol and drugs such as aspirin, valproic acid, ibuprofen, or zidovudine) can inhibit β-oxidation directly or through a primary effect on the mitochondrial genome or the respiratory chain itself. In some patients, infections and cytokines, or inborn errors of β-oxidation enzymes or the mitochondrial genome, may favor the appearance of drug-induced microvesicular steatosis. Nonalcoholic steatohepatitis may develop under conditions causing prolonged, microvesicular, and/or macrovacuolar steatosis. In this condition, chronic impairment of mitochondrial β-oxidation (causing steatosis) and the respiratory chain (increasing the production of ROS) lead to lipid peroxidation, which, in turn, may cause the diverse lesions of steatohepatitis, namely, necrosis, inflammation, Mallory's bodies, and fibrosis. Finally, mitochondria are involved in several forms of drug-induced cytolytic hepatitis, through inhibition or uncoupling of respiration or through a drug-induced or reactive metabolite-induced mitochondrial permeability transition. The latter effect commits hepatocytes to either apoptosis or necrosis, depending on the number of organelles that have undergone the permeability transition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007649815992
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  • 160
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    The Involvement of p53 in Dopamine-Induced Apoptosis of Cerebellar Granule Neurons and Leukemic Cells Overexpressing p53 (1999)
    Springer
    Cellular and molecular neurobiology 19 (1999), S. 261-276 
    Details
    ISSN: 1573-6830
    Keywords: Parkinson's disease ; catecholamines ; oxidative metabolites ; phosphorylation ; DNA damage ; apoptosis ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 1. The pathogenesis of the selective degeneration of the dopaminergic neurons in Parkinson's disease is still enigmatic. Recently we have shown that dopamine can induce apoptosis in postmitotic neuronal cells, as well as in other cellular systems, thus suggesting a role for this endogenous neurotransmitter and associated oxidative stress in the neuronal death process. 2. Dopamine has been shown to be capable of inducing DNA damage through its oxidative metabolites. p53 is a transcription factor that has a major role in determining cell fate in response to DNA damage. We therefore examined the possible correlation between dopamine-triggered apoptosis, DNA damage and levels of total phosphorylated p53 protein in cultured mouse cerebellar granule neurons. 3. Marked DNA damage and apoptotic nuclear condensation and fragmentation were detected within several hours of exposure to dopamine. An associated marked threefold increase in p53 phosphorylation was observed within this time window. Using a temperature-sensitive p53 activation system in leukemia LTR6 cells, were found that p53 inactivation dramatically attenuated dopamine toxicity. 4. We therefore conclude that DNA damage and p53 activation may have a role in mediating dopamine-induced apoptosis. Modulation of the p53 system may therefore have a protective role against the toxicity of this endogenous neurotransmitter and associated oxidative stress.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006933312401
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  • 161
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    Regulation of BAX and BCL‐2 expression in breast cancer cells by chemotherapy (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 107-117 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; Bax ; Bcl‐2 ; breast cancer ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Optimizing chemotherapeutic drug delivery strategies relies, in part, on identification of the most clinically effective sequence, dose, and duration of drug exposure. The combination of dose intensive etoposide (VP‐16) followed by cyclophosphamide has clinical efficacy in the treatment of advanced breast cancer. However, molecular mechanisms that underlie the effectiveness of this combination of chemotherapeutic agents have not been investigated. In this study we investigated regulation of BAX and BCL‐2 expression by VP‐16 and cyclophosphamide as a potential mechanism for the induction of breast cancer cell death induced by this regimen. There was a dose and time dependent increase in BAX expression in the breast cancer cell lines MCF‐7, MDA‐MB‐435S, and MDA‐MB‐A231 following in vitro treatment with 50–100 μM VP‐16. Elevation of BAX protein expression in the presence of VP‐16 alone did not correlate with reduced viability or induction of apoptosis in MCF‐7, MDA‐MB‐435S, or MDA‐MB‐A231. VP‐16 did effectively block the breast cancer cell lines evaluated (MCF‐7 and MDA‐MB‐435S) at G2/M phase of the cell cycle, confirming activity of the drug in vitro. MCF‐7 and MDA‐MB‐435S cells that were pre‐treated with VP‐16 and subsequently exposed to 1.0–12.0 μg/m1 4‐hydroperoxycyclophosphamide (4HC), an active metabolite of cyclophosphamide, had markedly reduced viability when compared to matched controls treated with either VP‐16 or 4HC individually. Consistent with this loss of viability, exposure of all three cell lines to the combination of VP‐16 and 4HC resulted in higher BAX protein levels than those observed following treatment with either single agent. This combination of chemotherapeutic agents also resulted in reduced BCL‐2 expression. These observations suggest that combination chemotherapy may derive its efficacy, in part, through coordinated regulation of specific gene products associated with apoptosis. Characterization of molecular events that underlie susceptibility of specific tumor cells to combination chemotherapeutic regimens may lead to additional improvements in treatment strategies for this disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006175811676
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  • 162
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    Hsp27 overexpression inhibits doxorubicin–induced apoptosis in human breast cancer cells (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 185-194 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; doxorubicin ; hsp27 ; topoisomerase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previously we demonstrated that heat shock protein 27 (hsp27) overexpression confers resistance to the chemotherapeutic agent doxorubicin in MDA–MB–231 breast cancer cells. Since induction of apoptosis is one underlying mechanism of chemotherapeutic drug action, we investigated the effect of hsp27 overexpression on doxorubicin–induced apoptosis, finding that hsp27 protects MDA–MB–231 cells from apoptosis. We also examined expression of the doxorubicin target, topoisomerase II (topo II), in control and hsp27–overexpressing stable transfectants, as topo II expression is important for both drug sensitivity and the initiation of apoptosis by doxorubicin. The relative levels of both topo IIα and β were higher in the controls than the hsp27–overexpressing clones, suggesting that the apoptotic protective effect of hsp27 overexpression in MDA–MB–231 cells is associated with altered topo II expression.abstract
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006207009260
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  • 163
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    Synergistic action of apoptosis induced by eicosapentaenoic acid and TNP‐470 on human breast cancer cells (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 147-158 
    Details
    ISSN: 1573-7217
    Keywords: angiogenesis inhibitor ; apoptosis ; Bcl‐2 ; breast cancer ; eicosapentaenoic acid ; TNP‐470
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of eicosapentaenoic acid (EPA) and an angiogenesis inhibitor (TNP‐470) on the suppression of breast cancer cell growth were examined in five human breast cancer cell lines (MDA‐MB‐231, T‐47D, MCF‐7, KPL‐1, and MKL‐F). In all five cell lines, EPA and TNP‐470 alone both showed tumor growth inhibition in a time‐ and dose‐dependent manner, and in combination, a synergistic effect was seen at high concentrations. EPA plus TNP‐470 treatment evoked apoptosis as confirmed by the appearance of sub G1 populations, by DNA fragmentation, and by cell morphology. With the combination, the expression of Bax and Bc1‐xS, the apoptosis‐enhancing proteins, was more up‐regulated and that of Bcl‐2 and Bcl‐xL, the apoptosis‐suppressing proteins, was more down‐regulated compared to the use of EPA or TNP‐470 alone, suggesting that their synergistic effect was due to an acceleration of apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006283131240
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  • 164
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    Glycogen‐rich carcinomas of the breast display unique characteristics with respect to proliferation and the frequency of oligonucleosomal fragments (1999)
    Springer
    Breast cancer research and treatment 57 (1999), S. 215-219 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; glycogen‐rich breast carcinoma ; prognosis ; proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We determined the proliferation rate and apoptotic activity of glycogen‐rich carcinomas of the breast as opposed to non‐clear cell tumors by means of MIB‐1 immunohistochemistry and in situ detection of oligonucleosomal fragments (TUNEL reaction). The retrospective biopsy series included six invasive clear cell carcinomas of the glycogen‐rich type as well as 15 randomly selected cases of invasive ductal carcinoma without evidence of glycogen storage. Three patients in the clear cell group and seven patients in the control cohort developed lymph‐node metastasis. The MIB‐1 labeling index of glycogen‐rich carcinomas averaged 9.05%, while that of the controls was 30.03%. Apoptotic nuclei were present in a mean of 1.26% of glycogen‐rich carcinoma cells. The control tumors exhibited an average apoptotic frequency of 5.85%. Tumor size, hormone receptor status, and presence or absence of lymph node involvement were found not to correlate with either proliferation or apoptosis. We conclude that glycogen‐rich breast carcinomas are characterized by a peculiar ‘low proliferation‐low apoptosis’ cell kinetic profile. The aggressive clinical behavior of these neoplasms may possibly be accounted for by an ineffective apoptotic elimination of otherwise slowly proliferating tumor cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006285819701
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  • 165
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    Maitotoxin Induces Calpain But Not Caspase-3 Activation and Necrotic Cell Death in Primary Septo-Hippocampal Cultures (1999)
    Springer
    Neurochemical research 24 (1999), S. 371-382 
    Details
    ISSN: 1573-6903
    Keywords: Calpain ; caspases ; maitotoxin ; necrosis ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Maitotoxin is a potent toxin that activates voltage and receptor-mediated Ca2+ channels, resulting in Ca2+ overload and rapid cell death. We report that maitotoxin-induced cell death is associated with activation of calpain but not caspase-3 proteases in septo-hippocampal cell cultures. Calpain and caspase-3 activation were examined by accumulation of protease-specific breakdown products to α-spectrin. Cell death manifested exclusively necrotic-like characteristics including round, shrunken nuclei, even distribution of chromatin, absence of DNA fragmentation and failure of protein synthesis inhibition to reduce cell death. Necrotic cell death was observed in neurons and astroglia. Calpain inhibitor II inhibited calpain-specific processing of α-spectrin and significantly reduced cell death. The pan-caspase inhibitor, Z-D-DCB, nominally attenuated cell death. Results suggest that: (1) calpain, but not caspase-3, is activated as a result of maitotoxin-induced Ca2+ influx; (2) necrotic cell death caused by maitotoxin exposure is partially mediated by calpain activation; (3) maitotoxin is a useful tool to investigate pathological mechanisms of necrosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020933616351
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  • 166
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    Synergistic cooperation between c-Myc and Bcl-2 in lymph node progression of T1 human breast carcinomas (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 39-45 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; Bcl-2 ; breast cancer ; c-Myc ; metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The overexpression of Bcl-2, an anti-apoptotic oncogene, identifies human T1 breast cancer patients who have an increased risk of lymph-node metastasis. We examined in these patients (n=142) whether the c-Myc oncogene influences metastatic progression in conjunction or not with Bcl-2 expression and the loss of apoptosis in tumors. The association between Bcl-2 and lymph-node metastasis was only significant when c-Myc was concomitantly expressed (χ2 test, p=0.008). Moreover, very large associations (pOR=6.4) between c-Myc and lymph-node metastasis were observed among Bcl-2 positive tumors and tumors with loss of apoptosis (pOR=8.4). In contrast, the metastatic advantage linked to Bcl-2 was decreased (pOR=2) when c-Myc was not coexpressed. It is concluded that the synergism between Bcl-2 and c-Myc oncogenes may promote metastasis in breast tumors, linked to loss of apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006120006471
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  • 167
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    Insulin‐like growth factor (IGF)‐I rescues breast cancer cells from chemotherapy‐induced cell death – proliferative and anti‐apoptotic effects (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 1-10 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; doxorubicin ; IGF‐I ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Insulin‐like growth factor (IGF)‐I protects many cell types from apoptosis. As a result, it is possible that IGF‐I‐responsive cancer cells may be resistant to apoptosis‐inducing chemotherapies. Therefore, we examined the effects of IGF‐I on paclitaxel and doxorubicin‐induced apoptosis in the IGF‐I‐responsive breast cancer cell line MCF‐7. Both drugs caused DNA laddering in a dose‐dependent fashion, and IGF‐I reduced the formation of ladders. We next examined the effects of IGF‐I and estradiol on cell survival following drug treatment in monolayer culture. IGF‐I, but not estradiol, increased survival of MCF‐7 cells in the presence of either drug. Cell cycle progression and counting of trypan‐blue stained cells showed that IGF‐I was inducing proliferation in paclitaxel‐treated but not doxorubicin‐treated cells. However, IGF‐I decreased the fraction of apoptotic cells in doxorubicin‐ but not paclitaxel‐treated cells. Recent work has shown that mitogen‐activated protein kinase (MAPK) and phosphotidylinositol‐3 (PI‐3) kinase are activated by IGF‐I in these cells. PI‐3 kinase activation has been linked to anti‐apoptotic functions while MAPK activation is associated with proliferation. We found that IGF‐I rescue of doxorubicin‐induced apoptosis required PI‐3 kinase but not MAPK function, suggesting that IGF‐I inhibited apoptosis. In contrast, IGF‐I rescue of paclitaxel‐induced apoptosis required both PI‐3 kinase and MAPK, suggesting that IGF‐I‐mediated protection was due to enhancement of proliferation. Therefore, IGF‐I attenuated the response of breast cancer cells to doxorubicin and paclitaxel by at least two mechanisms: induction of proliferation and inhibition of apoptosis. Thus, inhibition of IGF‐I action could be a useful adjuvant to cytotoxic chemotherapy in breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006208721167
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  • 168
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    Role of endothelial cell survival and death signals in angiogenesis (1999)
    Springer
    Angiogenesis 3 (1999), S. 101-116 
    Details
    ISSN: 1573-7209
    Keywords: angiogenesis ; apoptosis ; cell death ; endothelial cell ; neovascularization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Angiogenesis, the process of new microvessel development, is encountered in a select number of physiological processes and is central to the pathogenesis of a wide variety of diseases. There is now convincing evidence that regulated patterns of endothelial cell survival and death, a process known as apoptosis, play a central role in the periodic remodeling of the vasculature, and in the timely evolution and regression of angiogenic responses. In this review we discuss the current evidence suggesting a role for inducers and inhibitors of angiogenesis as well as other mediators that modify endothelial cells functions in the survival and death of endothelial cells. We also discuss how dysregulation of apoptosis can lead to aberrant angiogenesis as demonstrated in the pathogenesis of retinopathy of prematurity and cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009053411094
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  • 169
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    Differential sensitivity of human mammary epithelial and breast carcinoma cell lines to curcumin (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 269-278 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; breast carcinoma ; cell cycle ; curcumin ; cytotoxicity ; gene expression ; RT‐PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Curcumin has anti‐inflamatory, antiproliferative, and antitumor effects. To understand the chemopreventive mechanism of curcumin against human malignancies, the cellular and molecular changes induced by this agent in human mammary epithelial (MCF‐10A) and breast carcinoma (MCF‐ 7/TH) cell lines were investigated. The human multidrug‐ resistant breast cancer cell line was 3.5 fold more sensitive to curcumin than the mammary epithelial cell line. Even though both cell lines accumulated a similar amount of curcumin, a significantly higher percentage of apoptotic cells was induced in breast cancer cells compared to a very low percentage of apoptosis in mammary epithelial cells. Incubation of breast cancer cells with 20 and 40 μM curcumin for 24 h induced G2 block and sub‐ G0/G1 cell population, respectively. Curcumin treatment caused a reduction in the expression of Ki67, PCNA, and p53 mRNAs in breast cancer cells. The human mammary epithelial cell line showed a down‐regulation of p21 mRNA and an up‐regulation of Bax mRNA expression with curcumin treatment. The results suggest that apoptosis is involved in the curcumin‐induced inhibition of tumor cell growth, and genes associated with cell proliferation and apoptosis may be playing a role in the chemopreventive action of curcumin. Abbreviations: EGF: epidermal growth factor; D-MEM: Dulbecco' Modified Eagle Medium; EDTA: ethylene diamine tetra‐acetic acid; PBS: phosphate buffered saline; TdT: terminal deoxynucleotidyl transferase; FBS: fetal bovine serum; RT‐PCR: reverse transcription‐polymerase chain reaction; PCNA: proliferating cell nuclear antigen; TNF: tumor necrosis factor; TPA: 12‐tetradecanoyl‐phorbol‐13‐acetate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006170224414
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  • 170
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    Neo-adjuvant chemotherapy for operable breast cancer induces apoptosis (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 263-269 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; neo-adjuvant chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The use of neo-adjuvant chemotherapy (often referred to as pre-operative or primary chemotherapy) represents a major change in the management of breast cancer as a systemic disease. Laboratory studies have shown that many anti-cancer agents with differing modes of action achieve cytotoxic effects by inducing apoptosis. In this study, we investigated the induction of apoptosis by neo-adjuvant chemotherapy in human breast cancer. The aim was to determine whether a correlation existed between post chemotherapy apoptotic index (AI) and clinical response and patients' survival. Our results indicate that apoptosis is induced by neo-adjuvant chemotherapy and that the response is variable. Our data show that post chemotherapy AI correlated with clinical response and increased patient survival, including both relapse (disease) free survival and overall survival. Post-neo-adjuvant chemotherapy AI levels in primary breast cancer may possibly predict an individual patient's overall response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006194921139
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  • 171
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    The Fas/Fas‐ligand system: a mechanism for immune evasion in human breast carcinomas (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 245-253 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; breast carcinoma ; immunology ; tolerance/suppression ; tumor immunology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Breast tumors are frequently associated with a predominantly lymphocytic infiltrate, which constitutes an immune response against the tumor. In spite of this massive infiltrate, the immune response appears to be inefficient and the tumor is able to evade it. We propose that in breast cancer, tumor escape from immunological surveillance results from the induction of apoptosis of Fas‐bearing activated lymphocytes by FasL‐bearing breast cancer cells. To test this proposal we studied the expression of FasL by human breast carcinomas and the MCF‐7 breast cancer cell line by RT‐PCR, immunohistochemistry, and Western Blot. Moreover, we describe the presence of apoptosis and Fas expression in the lymphocytic population surrounding the tumor. Strong membranous and cytoplasmic staining was detected in ductal carcinomas and hyperplastic breast tissue, but it was absent from normal breast tissue. No staining was found in normal glands in the non‐tumor quadrant; however, the normal appearing ducts surrounding the carcinoma (tumor quadrant) showed intense immunoreactivity. Apoptosis was found predominantly among the lymphocytic population, as well as in the blood vessels and fibro‐fatty tissue close to the tumor. Further characterization of apoptotic cells demonstrated that they were CD3+ cells. Our results suggest the breast tumors may elude immunological surveillance by inducing, via the Fas‐FasL system, the apoptosis of activated lymphocytes. Recent data have demonstrated FasL RNA in other tumor types. Upregulation of FasL expression in hyperplastic and normal breast ducts close to the tumor also suggests a possible role in early neoplastic transformation and proliferation. Abbreviations: Con A: concanavalin A; FasL: Fas ligand; RT-PCR: reverse transcription+polymerase chain reaction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006102601215
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  • 172
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    Differential effects of chemotherapeutic agents on the Bcl‐2/Bax apoptosis pathway in human breast cancer cell line MCF‐7 (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 73-83 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; Bax ; Bcl‐2 ; breast ; chemotherapy ; estradiol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study explored the effects of three commonly used chemotherapeutic agents on the Bcl‐2/Bax apoptosis pathway and the interaction of these chemotherapeutic drugs with the estradiol‐mediated regulation of this pathway. Our results showed that: (1) Treatment of MCF‐7 cells with Adriamycin resulted in time‐ and concentration‐dependent decreases in Bcl‐2 and increases in Bax mRNA and protein levels. (2) Camptothecin elicited similar trends on Bcl‐2 and Bax as Adriamycin, while etoposide, at 50–100 fold (1–5 μM) the effective concentration of Adriamycin and camptothecin, only resulted in an increase in Bax mRNA levels. (3) Adriamycin and camptothecin, but not etoposide, were effective in suppressing estradiol‐stimulated increases in Bcl‐2 mRNA levels. Our study provides evidence that the Bcl‐2/Bax apoptosis pathway may be differentially regulated by chemotherapeutic agents. In addition, interaction between these agents and estradiol on the Bcl‐2/Bax apoptosis pathway may also exist.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006190802590
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  • 173
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    Overexpression of basic fibroblast growth factor (FGF–2) downregulates Bcl–2 and promotes apoptosis in MCF–7 human breast cancer cells (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 151-165 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; basic FGF ; Bax ; Bcl–2 ; breast cancer ; MCF–7 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Basic fibroblast growth factor (bFGF, FGF–2), a classical transforming factor, mitogen, and survival factor in multiple cell types, and has a paradoxic role in mammary epithelial cell transformation and proliferation. We have also demonstrated that recombinant FGF–2 uncharacteristically promotes cell death in MCF–7 human breast cancer cells. In this study, we investigated the effects of FGF–2 overexpression on survival in the same MCF–7 cells. In eight breast cancer cell lines and two nontransformed mammary epithelial cell lines, we demonstrated that high levels of Bcl–2 are only expressed in cells with undetectable levels of FGF–2 on western blot. In retrovirally transduced MCF–7 cells expressing both cytoplasm– and nucleus–localizing FGF–2 species and ones expressing only cytoplasm–localizing FGF–2 species, Bcl–2 levels were strongly decreased at both the mRNA and protein levels. Immunoprecipitation of Bax demonstrated a decreased association of Bax with Bcl–2 in these cells. Levels of Bax did not correlate with expression of FGF–2 in the 10 cell lines or in MCF–7 cells. The clonogenic potential of MCF–7 cells in tissue culture was decreased by the expression of FGF–2 and was additively suppressed by the chemotherapeutic agents etoposide and 5–fluorouracil in a dose and time dependent manner. MCF–7 cells overexpressing FGF–2 had a greater rate of programmed cell death at baseline and in response to etoposide and 5–fluorouracil in a TUNEL assay by immunofluorescent microphotography and by flow cytometric quantitation. The pro–apoptotic effect of FGF–2 overexpression on the chemosensitivity of these cells was confirmed by quantitative morphologic determination. These data demonstrate that the expression of FGF–2 downregulates Bcl–2 and promotes programmed cell death in MCF–7 human breast cancer cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006258510381
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  • 174
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    Local signals induce CCAAT/enhancer binding protein-δ (C/EBP-δ) and C/EBP-β mRNA expression in the involuting mouse mammary gland (1999)
    Springer
    Breast cancer research and treatment 58 (1999), S. 57-63 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; C/EBP ; involution ; mammary gland
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The repeated lactation cycles in the mammary gland offer a unique environment for the study of cell growth, differentiation, and death. The CCAAT/enhancer binding proteins (C/EBPs) are a family of transcription factors important in growth control and differentiation in many tissues. Our laboratory and others have shown that C/EBP-δ and C/EBP-β mRNA expression is closely associated with normal mouse mammary gland involution. To examine the relative influence of local versus systemic factors in C/EBP expression and tissue remodeling, a gland sealing mouse model was used. Mice with unilateral sealing continue to lactate and nurse pups via nonsealed glands, while sealed glands initiate involution. The expression of C/EBP-α, β and δ mRNA was investigated in sealed and nonsealed nursing glands. In situ apoptosis was documented and glandular morphology was also examined. C/EBP-δ mRNA levels are low in nonsealed glands, but are rapidly and transiently induced in sealed glands by 24 h. C/EBP-β mRNA expression is also relatively low in nonsealed glands, but is induced in sealed glands within 72 h. Expression of the apoptosis-associated mRNAs encoding bax and TRPM-2 is also induced in sealed glands by 24–48 h. Apoptosis and a moderate degree of tissue remodeling occur within the sealed glands in spite of systemic hormone levels capable of sustaining lactation. These data demonstrate that local factors are sufficient to induce C/EBP-β and C/EBP-δ in the mouse mammary gland. In addition, mammary epithelial apoptosis and glandular remodeling occur in sealed glands, confirming a critical role for local factors in mammary involution.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006381906288
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  • 175
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    The pure antiestrogen ICI 182780 is more effective in the induction of apoptosis and down regulation of BCL‐2 than tamoxifen in MCF‐7 cells (1999)
    Springer
    Breast cancer research and treatment 58 (1999), S. 87-97 
    Details
    ISSN: 1573-7217
    Keywords: antiestrogens ; apoptosis ; BCL‐2 ; breast cancer ; MCF‐7 ; tamoxifen ; ZM 182780
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is increasing evidence that induction of apoptosis by antihormones is an important mechanism in regard to their growth inhibitory action on hormone dependent tumors. In this report we have compared the efficiency of tamoxifen (Tam) and the pure antiestrogen ICI 182780 (ZM) to induce apoptosis in the estrogen dependent breast cancer cell line MCF‐7. Clear evidence for induction of apoptosis could be demonstrated after treatment with both antiestrogens. Application of the pure antiestrogen ZM led to a significantly higher induction of apoptosis compared to the partial agonistic compound Tam. The ability of the two compounds to induce apoptosis correlated with their growth inhibitory action. On the molecular level administration of ZM led to a time dependent steady decrease of BCL‐2 mRNA and protein. Administration of Tam also initially decreased the expression of BCL‐2. In contrast to ZM treatment, BCL‐2 expression increased again after 8 h of incubation with Tam. After 96 h Tam treated cells expressed BCL‐2 levels nearly as high as untreated cells. In general, ZM decreased BCL‐2 levels more effectively than Tam. Our results demonstrate that ZM and Tam possess quantitative and qualitative differences in their ability to down regulate BCL‐2 expression. The higher ability of the pure antiestrogen to down regulate BCL‐2 expression may explain the superiority of the pure antiestrogen to induce apoptosis and to inhibit the growth of MCF‐7 cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006338123126
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  • 176
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    Cure of colon cancer metastasis in rats with the new lipid A OM 174. Apoptosis of tumor cells and immunization of rats (1999)
    Springer
    Clinical & experimental metastasis 17 (1999), S. 299-306 
    Details
    ISSN: 1573-7276
    Keywords: cancer immunotherapy ; lipid A ; in vivo ; apoptosis ; immunization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The antitumoral effect of the new lipid A OM 174 was investigated in a model of colon cancer in rats. Peritoneal carcinomatosis were induced in BDIX rats by intraperitoneal injection of syngeneic PROb cancer cells. The treatment started 2 weeks later, when rats had macroscopic peritoneal nodules. An antitumoral effect was first obtained with OM 174 intraperitoneally injected, then an intravenous treatment was developed. When injected 15 times intravenously, at the dose of 1 mg/kg, 2 days apart, OM 174 induced the complete regression of tumors and hemorrhagic ascitis in 90% of the tumor-bearing rats, whereas all the untreated rats died of their tumors. To our knowledge, this treatment is the most effective ever applied to macroscopic tumors. Furthermore, the treatment induced the immunization of rats since the reinjection of PROb tumor cells in OM 174-cured rats did not cause the formation of new tumors while injection of another syngenic colon tumor cells did. Only in treated rats tumors were infiltrated with lymphocytes, macrophages and fibroblasts. The treatment did not increase necrosis but generated apoptotic areas. OM 174 was not directly toxic for tumor cells, and thus the observed effect involved the host-mediated antitumor reaction. Therefore we hypothesize that OM 174 therapy induces tumor cell apoptosis, stimulates the phagocytosis of apoptotic bodies and then activates immune system by antigen presentation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006663017149
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  • 177
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    Apoptosis, Heart Failure, Ischemic Heart Disease (1999)
    Springer
    Heart failure reviews 4 (1999), S. 1-9 
    Details
    ISSN: 1573-7322
    Keywords: apoptosis ; heart failure ; ischemia/reperfusion ; free radicals ; antioxidants ; phospholipids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cardiomyocytes die by apoptosis in addition to necrosis under a variety of pathological conditions including heart failure, cardiomyopathy, and ischemia/reperfusion. This review summarizes current status of the literature demonstrating evidence of apoptotic cell death in heart failure and ischemic heart disease. Apoptotic cells have been detected in failing hearts of human and dog. Ischemia up to 2 hr does not induce apoptosis, but reperefusion of ischemic heart can trigger apoptosis and DNA fragmentation. Apoptosis appears to occur in a varity of animal species including mouse, rat, rabbit, swine, dog and human suggesting that this is not species-specific. Striking similarities exist between the mechanisms of reperfusion injury and apoptosis: both involve free radicals, Ca2+ and phospholipids. Evidence exists in the literature to indicate role of oxygen free radicals and phospholipids in apoptotic cell death induced by ischemia and reperfusion. Apoptotic cell death in rat heart was inhibited by free radical scavengers or antioxidants.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009876508989
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  • 178
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    Mitochondrial Function in Heart Failure (1999)
    Springer
    Heart failure reviews 4 (1999), S. 229-244 
    Details
    ISSN: 1573-7322
    Keywords: heart failure ; mitochondria ; energy metabolism ; ageing ; adenine nucleotide ; translocator ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Experimental and clinical studies have detected an impaired respiratory function of cardiomyocyte mitochondria in heart failure. Since the reasons for heart failure are manifold, so is mitochondrial involvement. Characteristics of mitochondrial participation in heart failure are as follows: (1) Inherited or acquired mutations of the mitochondrial or nuclear genome cause defects in different mitochondrial components, eventually resulting in cardiomyopathy. (2a) Oxidative stress depresses mitochondrial function. This occurs slowly and inevitably in the 'physiological' process of ageing, but rapidly in “pathophysiologic” conditions such as post-ischemic reperfusion. (2b) Free radicals damage mitochondrial DNA, proteins, and membrane lipids. Interactions between altered membrane lipids, respiratory chain components, and carrier proteins further enhance mitochondrial dysfunction. (3) Mitochondrial energy transfer via the adenine nucleotide translocator (ANT) and the mitochondrial creatine kinase is disturbed in heart failure. Especially an altered expression and a functional impairment of the ANT seems to be involved in the disturbed energy metabolism of dilated and inflammatory cardiomyopathy. (4) Mitochondria are mainly involved in the initiation and modulation of the process of programmed cell death (apoptosis). (5) Triggered by a variety of conditions during cellular dysfunction mitochondrial membrane permeability suddenly increases, followed by the collapse of the membrane potential, thus abolishing energy production and further aggravating cellular damage. (6a) Increased levels of cytokines, in particular TNF-α, in heart failure and cardiomyopathy modulate mitochondrial function. (6b) Cytokines activate the generation of nitric oxide and heat shock proteins, thus further depressing or preserving mitochondrial activity. These main mechanisms of active and passive participation of mitochondria in heart failure are reviewed in this article. At present, most of them are not completely resolved and some are still hypothetical.
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    URL: http://dx.doi.org/10.1023/A:1009810023405
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  • 179
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    Changes in Gene Expression during the Transition from Compensated Hypertrophy to Heart Failure (1999)
    Springer
    Heart failure reviews 4 (1999), S. 361-378 
    Details
    ISSN: 1573-7322
    Keywords: gene expression ; heart failure ; hypertrophy ; cell signaling ; E-C coupling ; extracellular matrix ; neurohormones ; growth factors ; cytokines ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract With the advancement in molecular techniques for characterizing genes and the use of animal models as tools to study heart failure, considerable progress has been made in improving our understanding of the regulation and function of genes associated with heart failure. Studies now indicate that autocrine/paracrine factors including neurohormones such as norepinephrine, angiotensin II, proinflammatory cytokines and peptide growth factors produced locally in the heart may affect myocyte growth and function through intricate signaling mechanisms. While changes in gene expression for the proteins involved in cell signaling may lead to myocyte hypertrophy and/or apoptosis, alteration in calcium homeostasis, excitation-contraction coupling and the extracellular matrix also contribute to systolic and diastolic dysfunction leading to heart failure. Thus, heart failure is a complex process, which involves changes in expression of multiple genes. With the advent of new techniques involving microarray and gene chip technology, it is now possible to define and/or identify sets of genes involved in heart failure. The purpose of this review is to provide an overview of molecular signals, intracellular signaling mechanisms and the changes in gene expression associated with the transition from compensated hypertrophy to failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009855720081
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  • 180
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    Modulation of the malignant phenotype of human prostate cancer cells by N-(4-hydroxyphenyl)retinamide (4-HPR) (1999)
    Springer
    Clinical & experimental metastasis 17 (1999), S. 255-263 
    Details
    ISSN: 1573-7276
    Keywords: apoptosis ; 4-HPR ; invasion ; prostate cancer ; retinoid receptors ; vimentin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A long latent period of 20 to 30 years may be involved in the multistep process of carcinogenesis represented by prostatic intraepithelial neoplasia (PIN) in the prostate. It is, therefore, possible that progression to a malignant state could be blocked or reversed during this time. Retinoids not only have the ability to block steps in the process of carcinogenesis but they may also modulate or reverse some malignant characteristics of cancer cells. This study focuses on the ability of N-(4-hydroxyphenyl)-retinamide (4-HPR), a synthetic retinoid, to reverse malignant characteristics towards a normal phenotype, using the human prostate carcinoma cell line DU-145. These malignant characteristics include abnormal cell proliferation, intermediate filament expression, motility, invasion, and cell survival. Results show that 1 μM and 10 μM 4-HPR caused 31% and 96% inhibition of growth, while all-trans retinoic acid (ATRA) produced similar effects at 10 and 100 μM, making 4-HPR ten times more effective than ATRA. While DU-145 cells show strong immunostaining for vimentin, treatment with 1 μM 4-HPR for eight days caused a marked decrease in vimentin staining. This was accompanied by a change from an elongated to an epithelial cell morphology. Densitometric analysis of Western blots for vimentin showed a 53% decrease in vimentin expression in 1 μM 4-HPR treated cells. Concomitant with the decrease in vimentin expression, cell motility and invasive ability also decreased by 32% and 52%, respectively. Growth inhibition was accompanied by DNA fragmentation and apoptosis. Exposure of cells to 1 μM 4-HPR caused a marked upregulation of nuclear retinoid receptors RARα and a detectable expression of RARγ. These results suggest that inhibition of growth and vimentin expression, and induction of apoptosis by 4-HPR in prostate cancer cells may occur via a receptor-mediated mechanism involving transrepression of AP-1 by retinoid receptors. We propose that vimentin may serve as a useful intermediate marker for early detection of prostate cancer in biopsy specimens and that 4-HPR may be effective in blocking several steps in prostate carcinogenesis as well as the progression of PIN to invasive carcinoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006665616932
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  • 181
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    Activated Oxygen Species in Heart Failure (1999)
    Springer
    Heart failure reviews 4 (1999), S. 1-12 
    Details
    ISSN: 1573-7322
    Keywords: free radicals ; antioxidants ; heart failure ; apoptosis ; ischemia ; reperfusion injury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Congestive heart failure (CHF) is defined by inability of the heart to provide adequate blood flow, oxygen, and nutrients to tissues and organs. There is now overwhelming evidence suggesting that oxygen-derived free radicals are involved in the pathogenesis of CHF. In vitro studies suggest that the highly toxic radical species damage sub-cellular membranes leading to the disruption in excitation-contractile coupling and eventually the dysfunction of the myocardium. In addition, these radicals destroy nitric oxide, a potent signaling molecule responsible for maintaining cardiovascular tone. Antioxidants hold great promise in minimizing the damage occurring as a result of the excessive generation of the free radicals during ischemia/reperfusion injury and CHF.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009816207172
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  • 182
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    Molecular Mechanisms of Apoptosis in Heart Failure (1999)
    Springer
    Heart failure reviews 4 (1999), S. 1-7 
    Details
    ISSN: 1573-7322
    Keywords: apoptosis ; p53 ; adenovirus ; Bcl-2 ; ventricular myocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract One of the most compelling issues to impact on contemporary cardiology to date is undoubtedly the concept of apoptosis or programmed cell death. Apoptosis, while crucial for normal embryonic development has been implicated in the pathogenesis of a number of cardiac pathologies including ischemia, oxidative stress injury, infarction and more recently heart failure. The loss of functional cardiac myocytes through activation of an apoptotic program may ultimately contribute to ventricular remodeling and the demise of ventricular function incompatible with the body's needs. The molecular mechanisms that underlie cardiac cell apoptosis remain poorly defined, however, there is increasing awareness that external as well as internal factors such tumor suppressor protein p53, cytokines including TNFα and mitochondria are potential triggers of cardiac apoptosis. Therefore, a better understanding of the role played by these factors would facilitate the advent of therapeutic agents to modulate inappropriate cardiac cell loss as a means to preserve cardiac function and prevent heart failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009824424919
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  • 183
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    The Role of Apoptosis in Normal and Abnormal Embryonic Development (1999)
    Springer
    Journal of assisted reproduction and genetics 16 (1999), S. 512-519 
    Details
    ISSN: 1573-7330
    Keywords: apoptosis ; gametogenesis ; embryogenesis ; maldevelopment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Programmed cell death or apoptosis is a widespread biological phenomenon. Apoptosis is characterized by typical cell features such as membrane blebbing, chromatin condensation, and DNA fragmentation. It involves a number of membrane receptors (e.g., Fas, TNFR) and a cascade of signal transduction steps resulting in the activation of a number of cysteine proteases known as caspases. Disordered apoptosis may lead to carcinogenesis and participates in the pathogenesis of Alzheimer disease, Parkinson disease, or AIDS. Programmed cell death plays an important role in the processes of gamete maturation as well as in embryo development, contributing to the appropriate formation of various organs and structures. Apoptosis is one of the mechanisms of action of various cytotoxic agents and teratogens. Teratogen-induced excessive death of embryonic cells is undoubtedly one of the most important events preceding the occurrence of structural abnormalities, regardless of their nature. Therefore understanding the mechanisms involved in physiological as well as in disturbed or dysregulated apoptosis may lead to the development of new methods of preventive treatment of various developmental abnormalities. The present review summarizes data on the mechanisms of programmed cell death and concentrates on apoptosis involved in normal or disturbed gametogenesis and in normal and abnormal embryonic development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020541019347
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  • 184
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    Sperm Artificially Exposed to Antisperm Antibodies Show Altered Deoxyribonucleic Acid (1999)
    Springer
    Journal of assisted reproduction and genetics 16 (1999), S. 443-449 
    Details
    ISSN: 1573-7330
    Keywords: apoptosis ; immunology ; antisperm antibodies ; spermatozoa ; denaturing gradient gel electrophoresis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Our purpose was to assess sperm deoxyribonucleic acid (DNA) integrity after exposure to antisperm antibodies. Methods: Donor semen were divided and exposed to sera containing IgG, IgA, and IgM antisperm antibodies. Untreated portions served as the control. After incubation (1 hr, 23°C), the sperm were centrifuge-washed, resuspended, and incubated (23°C) for 2, 5, 7, or 9 days. Acridine orange staining and kinematic parameters were measured. The sentinel (17q21 from D17S855) and β-globin genes were amplified and analyzed using denaturing gradient gel electrophoresis. Results: Sperm preexposed to antisperm antibodies had deleted sentinel gene on days 7 and 9. The β-globin gene was intact. There were no differences in acridine orange staining. Conclusions: Sperm artificially exposed to antisperm antibodies resulted in a subtle deletion of genetic material. The DNA alteration process was slow and was undetectable at the gross level. More studies are needed to confirm the findings and determine whether DNA repair mechanisms can reverse the damage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020525726674
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  • 185
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    Estimation of wound age and VCAM-1 in human skin (1999)
    Springer
    International journal of legal medicine 112 (1999), S. 159-162 
    Details
    ISSN: 1437-1596
    Keywords: Key words VCAM-1 ; Selectins ; Wound age ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Notes: Abstract To estimate the age of skin wounds, the endothelial adhesion molecule VCAM-1 (CD 106) was detected in paraffin sections after autoclaving and using the ABC technique. The percentage of VCAM-1 positive blood vessels was determined after the blood vessels had been marked with PECAM-1 (CD 31). Low positive staining reactions were observed for VCAM-1 on endothelial cells of uninjured skin in 18% of the samples. In injured skin, 51% of the cases investigated showed a VCAM-1 expression. Strong positive staining reactions were observed 3 h at the earliest and 3.5 days at the latest after the time of injury. The immunohistochemical results for VCAM-1 differed significantly between the injured and uninjured skin (P 〈 0.01). In a few cases VCAM-1 was detected (n = 6) at low intensity in postmortem skin wounds and a moderate to strong expression of VCAM-1 is indicative of the vitality of the wound. The detection of VCAM-1 can be used for estimating the age of wounds in forensic applications if the degree of expression of further adhesion molecules, especially that of selectins, is taken into account.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004140050223
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  • 186
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    Electronic Resource
    Modulation of Antioxidant Enzymes and Apoptosis in Mice by Dietary Lipids and Treadmill Exercise (1999)
    Springer
    Journal of clinical immunology 19 (1999), S. 35-44 
    Details
    ISSN: 1573-2592
    Keywords: Dietary n-6 and n-3 PUFA ; treadmill exercise ; lipid peroxides ; splenocytes ; antioxidant enzymes ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The current experiments were designed to study the effect of dietary n-6 and n-3 polyunsaturated fatty acids on antioxidant enzyme activity and dexamethasone (DEX)-induced apoptosis in spleen cells of sedentary (Sed) and treadmill-exercised (Ex) ICR male mice. Two-month-old mice maintained on AIN 76 formula diet, supplemented with either 5% corn oil (CO) or 5% fish oil (FO) diets, were trained on a treadmill to run from 45 to 50 min 1 km/day, 6 days a week for 12 weeks. After 12 weeks of exercise, both Sed and Ex groups were sacrificed. Blood and various tissues, including spleen, were collected asceptically. Increased serum and spleen homogenate peroxide [malondialdehyde (MDA)] levels were observed in mice fed FO (n-3 PUFA) diets, compared to mice fed CO (n-6 PUFA). However, exercise did not alter MDA levels in either CO- or FO-fed mice. Feeding n-3 PUFA significantly increased superoxide dismutase (SOD), catalase, and glutathione peroxidase activity of spleen homogenates. Exercise also significantly increased SOD and peroxidase in CO-fed animals, whereas catalase, glutathione peroxidase, and glutathione transferase were higher in FO-fed mice, compared to the Sed group. Apoptosis and necrosis were quantitated in splenocytes incubated with or without 1 μM Dex in RPMI medium for 8 and 24 hr. Cells were stained with Annexin V and propidium iodide (PI) for apoptotic and necrotic cells. FO-fed mice showed higher apoptosis (64 vs 50%) and necrosis (40 vs 22%) in spleen cells than CO-fed mice. Cells from FO-fed mice, incubated in medium alone, showed increased apoptosis (112%) 24 hr after incubation, and necrosis (37 and 70%) at 8 and 24 hr of incubation, compared to CO-fed mice. In Ex group, apoptosis was increased in both CO- and FO-fed mice only at 24 hr after incubation. In summary, these results indicate that FO (n-3 PUFA-enriched) diets increase apoptosis and antioxidant enzyme activity in spleen cells, probably due to elevated lipid peroxides.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020562518071
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  • 187
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    TNF-Induced Signaling in Apoptosis (1999)
    Springer
    Journal of clinical immunology 19 (1999), S. 350-364 
    Details
    ISSN: 1573-2592
    Keywords: Tumor necrosis factor ; signaling ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Out of the almost 17 members of the TNF superfamily, TNF is probably the most potent inducer of apoptosis. TNF activates both cell-survival and cell-death mechanisms simultaneously. Activation of NF-kB-dependent genes regulates the survival and proliferative effects pf TNF, whereas activation of caspases regulates the apoptotic effects. TNF-induced apoptosis is mediated primarily through the activation of type I receptors, the death domain of which recruits more than a dozen different signaling proteins, which together are considered part of an apoptotic cascade. This cascade does not, however, account for the role of reactive oxygen intermediates, ceramide, phospholipases, and serine proteases which are also inplicated in TNF-induced apoptosis. This cascade also does not explain how type II TNF receptors which lack the death domain, induce apoptosis. Nevertheless, this review of apoptosis signaling will be limited to those proteins that makeup the cascade.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020546615229
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  • 188
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    A Portrait of the Bcl-2 Protein Family: Life, Death, and the Whole Picture (1999)
    Springer
    Journal of clinical immunology 19 (1999), S. 365-377 
    Details
    ISSN: 1573-2592
    Keywords: Bcl-2 family of proteins ; apoptosis ; cancer ; autoimmunity ; infection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The Bcl-2 family of proteins are important regulators of cell death. They are comprised of two opposing factions, the proapoptotic versus the antiapoptotic members. Both are required for normal development and cellular homeostasis of the immune system and other tissues. However, in certain circumstances they may participate in the development of disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020598632068
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  • 189
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    Intracerebral Production of Tumor Necrosis Factor-α, a Local Neuroprotective Agent, in Alzheimer Disease and Vascular Dementia (1999)
    Springer
    Journal of clinical immunology 19 (1999), S. 223-230 
    Details
    ISSN: 1573-2592
    Keywords: Dementia ; tumor necrosis factor-α ; apoptosis ; tau protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The local pattern of proinflammatory cytokine release was studied in Alzheimer disease (AD) and vascular dementia (VAD), by measuring intrathecal levels of IL-1β, IL-6, TNF-α, and its naturally occurring antagonists, soluble TNF receptors I and II. The cytokine levels were related to neuronal damage, as measured by the intrathecal tau concentration, to cerebral apoptosis assessed by levels of Fas/APO-1 and bcl-2, and to clinical variables. In vitro analysis was performed to study the effect of TNF-α on the production of bcl-2, an antiapoptotic factor, by human neuronal cells. Patients with both AD and VAD displayed significantly higher intrathecal levels of TNF-α compared to controls. In addition, patients with AD showed significantly negative correlations between the intrathecal levels of TNF-α and the levels of Fas/APO-1 as well as of tau protein. The level of bcl-2 in supernatants of TNF-α-exposed cultures of human neuronal cells was up to three times higher than in control supernatants. Our study demonstrates intrathecal production of TNF-α in patients with dementias, suggesting that this cytokine may have a neuroprotective role in these neurodegenerative conditions as evidenced by negative correlations between this cytokine and (i) levels of intrathecal Fas/APO-1 and (ii) levels of tau protein, both parameters closely related to brain damage. Our in vitro data suggest that TNF-α exerts its neuroprotective effect by stimulating neuronal cells to express bcl-2, a molecule which downregulates apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020568013953
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  • 190
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    Culture filtrates of Aspergillus fumigatus induce different modes of cell death in human cancer cell lines (1999)
    Springer
    Mycopathologia 146 (1999), S. 67-74 
    Details
    ISSN: 1573-0832
    Keywords: apoptosis ; Aspergillus fumigatus ; cell death ; culture filtrate(s) ; necrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Aspergillus fumigatus culture filtrate (CF) has a potent cytotoxic effect on three human cancer cell lines (DLKP, A549 and HEp-2) and initiates cell death by apoptosis but the execution of the apoptotic process is incomplete. DLKP cells treated with A. fumigatus CF demonstrate features associated with apoptosis but cytoplasmic and nuclear fragmentation were not observed and cells ultimately underwent necrosis. The apoptotic process commenced in A549 and HEp-2 cells upon exposure to CF, cell shrinkage was observed but membrane blebbing and apoptotic body formation were not detected and detached cells died by necrosis. In contrast, extensive nuclear fragmentation and apoptotic body formation were evident in DLKP and A549 cells treated with anti-neoplastic agents. This work indicates that A. fumigatus CF is cytotoxic to cancer cells and can initiate apoptosis but that the complete apoptotic pathway is not followed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007092112873
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  • 191
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    No correlation between RET immunostaining and the codon 918 mutation in sporadic medullary thyroid carcinoma (1999)
    Springer
    Langenbeck's archives of surgery 384 (1999), S. 60-64 
    Details
    ISSN: 1435-2451
    Keywords: Key words Sporadic medullary thyroid carcinoma (sMTC) ; Multiple endocrine neoplasia 2 (MEN 2) ; RET mutation ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Introduction: Medullary thyroid carcinoma (MTC) occurs sporadically or as part of the inherited cancer syndrome, multiple endocrine neoplasia (MEN) type 2. The MEN2 gene has been identified as the RET proto-oncogene. Mutations in the RET proto-oncogene are associated with the pathogenesis of MTC. Approximately 23–40% of sporadic MTCs (sMTCs) have a somatic RET codon 918 mutation within the catalytic core of the tyrosine kinase, which is a mutation found in over 98% of all MEN 2B cases as a germline mutation. Methods: In order to elucidate the role of this mutation, we examined 40 sMTCs for the codon 918 mutation. Simultaneously, we looked for overexpression of the RET protein by means of immunohistochemistry with a newly developed RET antibody. Results: In 8 of 40 tumors (20%), we were able to find a RET codon 918 mutation. Nine of 40 tumors (22.5%) showed immunoreactivity with the RET antibody. Conclusion: The presence of the somatic RET codon 918 mutations did not correlate with the presence of positive RET immunostaining.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004230050175
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  • 192
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    Electronic Resource
    Solitary fibrous tumor of the paranasal sinuses (1999)
    Springer
    European archives of oto-rhino-laryngology and head & neck 256 (1999), S. 233-236 
    Details
    ISSN: 1434-4726
    Keywords: Key words Solitary fibrous tumor ; Paranasal sinuses ; Immunohistochemistry ; CD34 antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although solitary fibrous tumors are well-recognized in the pleura, their occurrence in the paranasal sinuses is decidedly uncommon. We have encountered two cases of solitary fibrous tumors in the paranasal sinuses and report the clinicopathological findings including CD34 immunoreactivity. One tumor arose in a 55-year-old Japanese businessman and the other in a 53-year-old man who had been in the hospital for schizophrenia for 20 years. The tumors showed characteristic findings. Immunoperoxidase stains on paraffin sections showed staining of the cells for anti-vimentin, but there was no staining for anti-keratin, anti-S-100 protein, anti-desmin, anti-glial fibrillary acidic protein (GFAP), or anti-actin. Anti-CD34 monoclonal antibodies also reacted with these tumors, as those of the pleura generally do, and were found to be useful in diagnosing these tumors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004050050148
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  • 193
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    Immunohistochemical analysis of lymphocytic infiltration in the tumor microenvironment in patients operated on for laryngeal cancer (1999)
    Springer
    European archives of oto-rhino-laryngology and head & neck 256 (1999), S. 384-387 
    Details
    ISSN: 1434-4726
    Keywords: Key words Laryngeal cancer ; Tumor ; microenvironment ; Immunohistochemistry ; CD lymphocyte ; Infiltration intensity ; Prognostic value ; Lymph node metastases ; Survival time ; Differentiation grade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to evaluate semiquantitative and qualitative analysis of lymphocytic infiltrations in a neoplasm microenvironment in patients with laryngeal cancers and the correlation analysis between the intensitivity degree and composition of lymphocytic infiltration in foreseeing a survival time and probability of the appearance of lymph node metastases. Postoperative specimens from 43 patients (Upper Silesia region) operated on for laryngeal cancer in the 2nd ENT Department, Silesian Medical University in Zabrze between 1985 and 1995 all had unfavorable courses due to tumor recurrences. The patients’ ages ranged from 39 to 79 years (mean 57 years). Tissue specimens were subjected to routine processing. The degree of pathological changes was ascertained and immunohistochemical preparations of laryngeal tissue were prepared according to generally accepted methods. The following primary monoclonal antibodies were used: CD 3, CD 20, CD 43, CD 45 RO, CD 56. The distribution analysis of the intensity of the phenotype CD 43 evaluated the lymphocytic infiltration in relation to differentiation of the whole study group. The intensity of CD 43 cell infiltration increased in the group of patients with lymph node metastases. In patients with stage IV disease, a relationship was found between survival time and intensity of cell infiltrations with CD 43 and CD 45 RO lymphocytes. The influence of these two lymphocyte phenotypes in the patient subgroups – one after total laryngectomy with confirmed lymph node metastases and the other group without lymph node metastases – showed their prognostic value. Our analysis of lymphocytic infiltration, mostly of CD 43 cells, in the neoplasm microenvironment indicated a prognostic value for determining a shorter survival time and the possibility of lymph node metastases in patients with recurrences of cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004050050169
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  • 194
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    Overexpression of p53 nuclear protein in premalignant and malignant laryngeal lesions (1999)
    Springer
    European archives of oto-rhino-laryngology and head & neck 256 (1999), S. S56 
    Details
    ISSN: 1434-4726
    Keywords: Key words p53 nuclear marker ; Laryngeal ; hyperkeratosis ; Laryngeal carcinoma ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate the role of p53 nuclear protein mutations in the initiation and progression of laryngeal carcinoma, 111 premalignant and malignant laryngeal lesions (19 specimens with hyperkeratosis and 92 with carcinoma) were studied immunohistochemically. Overexpression of p53 was observed in 8 cases (42%) of laryngeal hyperkeratosis and 44 cases (47%) of laryngeal carcinoma. However, the expression of p53 showed no relationship to patients’ clinical courses. Our study confirms that p53 overexpression can be found in laryngeal carcinogenesis and is an early event but not a useful prognostic marker.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00014155
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  • 195
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    Fas-mediated apoptosis is attenuated in preneoplastic GST-P-positive hepatocytes isolated from diethylnitrosamine-treated rats (1999)
    Springer
    Cell biology and toxicology 15 (1999), S. 239-247 
    Details
    ISSN: 1573-6822
    Keywords: apoptosis ; bile acid ; diethylnitrosamine ; enzyme-altered foci ; Fas ; hepatocytes ; p53 ; preneoplastic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Previous reports have indicated that apoptosis is selectively decreased in enzyme-altered foci (EAF) in the livers of rats treated with a carcinogen. Here we have investigated the effects of an anti-Fas antibody (anti-Fas Ab) on EAF cells in vitro. Hepatocytes were isolated from rats treated repeatedly with diethylnitrosamine (DEN), whose livers contained glutathione S-transferase P (GST-P)-positive EAF. Subsequently, primary cultures of GST-P-positive and GST-P-negative hepatocytes were established and exposed to anti-Fas Ab. Anti-Fas Ab (4 μg/ml) preferentially induced apoptosis in GST-P-negative cells. Furthermore, GST-P-positive cells were shown to be resistant to p53-mediated apoptosis. We conclude that EAF hepatocytes are resistant to Fas-mediated apoptosis in vitro. This lack of response may explain the selective decrease in apoptosis in EAF.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007663729113
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  • 196
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    Different induction of adaptive response to ionizing radiation in normal and neoplastic cells (1999)
    Springer
    Cell biology and toxicology 15 (1999), S. 111-119 
    Details
    ISSN: 1573-6822
    Keywords: adaptive response ; apoptosis ; low-dose radiation ; neoplastic cells ; normal cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Since the beneficial effects of low-dose radiation (0.01 Gy) are usually observed in normal cells, we investigated whether the adaptive response was induced by low-dose radiation in neoplastic cells of different origin as well as in normal cells. Cell lines used in this experiment were as follows: mouse lymphocytes (NL); L929 cells established from mouse connective tissue; primary mouse keratinocytes (PK); line 308 from mouse papilloma; X-ray sensitive lymphoma cells, L5178Y-S and EL-4 cells from mouse lymphoma. The adaptive response was determined by cell survival and apoptosis. The involvement of apoptosis in the adaptive response was examined by ELISA and TUNEL assay. Adaptive response was induced by pretreatment with low-dose radiation of 0.01 Gy in normal cells such as NL, L929, and PK, but not in L5178Y-S, EL-4, and line 308 cells. In addition, the reduction of apoptosis by pretreatment with low-dose radiation was observed in NL, L929, and PK, but not in L5178Y-S, EL-4, and line 308 cells. These results suggested that the adaptive response could be induced by pretreatment with low-dose radiation and the phenomena were observed in normal cells, not in neoplastic cells. In addition, pretreatment with low-dose radiation reduced apoptosis, suggesting that an anti-apoptotic pathway may be involved in the adaptive response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007525531145
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  • 197
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    A reappraisal of the role of Zn2+ in TGF-β1-induced apoptosis in primary hepatocytes (1999)
    Springer
    Cell biology and toxicology 15 (1999), S. 381-387 
    Details
    ISSN: 1573-6822
    Keywords: apoptosis ; hepatocytes ; in situ end-labeling ; TGF-β1 ; Zn2+
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract There is now a wealth of information regarding the apoptotic mode of cell death and its importance in toxicological studies in many mammalian organs including the liver. In this study, we investigated the modulatory effects of the heavy metal Zn2+ on transforming growth factor-β1 (TGF-β1)-induced apoptosis in primary rat hepatocytes. Apoptosis induced by TGF-β1 (1 ng/ml) in hepatocytes was accompanied by nuclear condensation as assessed morphologically by staining with Hoechst 33258 and DNA cleavage as detected biochemically by in situ end-labeling, field inversion and conventional gel electrophoresis. Pretreatment with 100 μmol/L Zn2+ abrogated the nuclear condensation, in situ end-labeling, and DNA laddering in TGF-β1-treated hepatocytes. Surprisingly, Zn2+ did not inhibit the formation of high-molecular-weight DNA fragments (30–50 kbp to 250–300 kbp). These data provide evidence that Zn2+ exerts its effects on the endonucleases that act downstream in the execution phase of TGF-β1-induced apoptosis in hepatocytes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007606016901
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  • 198
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    Induction of apoptosis in human leukemia (HL-60) cells by skimmed milk digested with a proteolytic enzyme purified from Saccharomyces cerevisiae (1999)
    Springer
    Biotechnology techniques 13 (1999), S. 727-734 
    Details
    ISSN: 1573-6784
    Keywords: apoptosis ; cell-free extract ; proliferation inhibition ; protease B ; skimmed milk
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Apoptosis-inducing materials were produced by digesting bovine skimmed milk with cell-free extract of Saccharomyces cereviiae at pH 4.8. An enzyme involved in production of the materials was purified from the cell-free extract by successive column chromatography. The purified enzyme was homogeneous and identified as protease B by analyzing N-terminal amino acid sequence. Characteristics features of apoptosis were observed within 5 h of digested skimmed milk treatment as documented by DNA fragmentation, expression of phosphatidylserine. The inducing factors were recovered in the soluble fraction of 92% ethanol, suggesting that the factors were hydrophilic low molecular weight substances.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008946616614
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  • 199
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    Prognostic value of tumor-associated antigens immunoreactivity and apoptosis in medulloblastomas. An analysis of 73 cases (1999)
    Springer
    Brain tumor pathology 16 (1999), S. 37-44 
    Details
    ISSN: 1861-387X
    Keywords: Medulloblastoma ; Prognosis ; Tenascin ; Apoptosis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Medulloblastomas (MB) are the most common central nervous system malignancies in children. Numerous publications describe efforts to identify the predictive value of various patterns of MB pathology and immunohistochemistry, but received data appear to be controversial. Seventy-three patients with cerebellar MB were studied retrospectively. Tumor specimens were immunohistochemically examined with antibodies to various tumor-associated antigens. Also, apoptosis detection by the in situ end-labeling method was performed. Survival analysis was made using univariate and multivariate models. Tenascin immunoreactivity and apoptotic index (AI)〉or=1.5% were found to be closely associated with poor prognosis according to an univariate analysis (P=0.008 and 0.003, respectively). The multivariate Cox proportional hazard model exhibited independent prognostic value for the apoptotic rate only (P=0.023). Tumors with tenascin expression and AI〉or=1.5% significantly prevailed among MB with metastatic dissemination, whereas expression of c-erbB2 oncoprotein and epidermal growth factor receptor was found to be more typical for cases with local tumor recurrence. We came to the conclusion that tenascin immunoreactivity and AI were useful for individual MB prognosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02478900
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  • 200
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    A Novel Podophyllotoxin-Derived Compound GL331 Is More Potent than Its Congener VP-16 in Killing Refractory Cancer Cells (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 997-1002 
    Details
    ISSN: 1573-904X
    Keywords: GL331 ; VP-16 ; apoptosis ; cytotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. GL331 is a new homolog of VP-16, and has demonstrated more efficacious anti-cancer activity in both the in vitro and in vivo lymphoma systems. To extensively explore GL331's clinical value, we furthermore evaluate the cytotoxicity and apoptosis-inducing activity of GL331 in several human cell lines from cancers that are not normally treated with VP-16. Methods. By MTT and clonogenic survival assays, the cytotoxicities of GL331 and VP-16 were evaluated in a variety of cell lines including nasopharyngeal, hepatocellular, gastric, colon, cervical, and neuro-blastoma cancer types. Western blot analysis was performed to detect the MDR-1 level in these cell lines. By Annexin V-staining flow cytometry and detection of DNA ladders, the apoptosis-inducing activities of GL331 and VP-16 were also evaluated. Results. GL331 showed more efficacy than its congener VP-16 in killing cancer cells. The estimated ID50 of GL331 were 2.5 to 17-fold lower than those of VP-16. GL331 possessed more cell-killing activity even in MDR-1-overexpressing cell lines such as HCC36 and SW620. Its higher cytotoxicity could be attributed by the elevated ability to induce apoptotic cell death. Conclusions. GL331's overriding drug resistance and higher cancer cell-killing activity suggest its superiority in clinical cancer therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018971313256
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