Home Alone 2 Lost In New York (1992) 1080p
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At a school Christmas pageant, during Kevin's solo, his older brother Buzz embarrasses him; Kevin retaliates by pushing him, which causes the entire choir to fall, ruining the pageant. At home, Buzz makes a false apology to Kevin, which the family accepts. Kevin refuses to apologize for pushing Buzz over and berates his family for believing Buzz's lies and for wanting to spend Christmas in Florida. He storms off to the attic, wishing to have his own vacation alone.
\"Home Alone 2\" sends young Kevin McCallister, portrayed by Macaulay Culkin, to New York City, while his family flies to spend Christmas in Miami. When Kevin's family lands in Miami, they realize that they've lost Kevin. This time, instead of being home alone, he's lost in New York City.
The setting may have changed, and the stakes raised, but again, the story is the same. Kid gets lost, this time by a mishap at the airport (that's right, he made it there this time!), and instead of being stuck at home, he's in a strange new place: the strangest (and biggest) place of them all. Instead of being unknowns, the Wet Bandits are fresh prison escapees, who arrive in New York in a fish truck. Instead of a scary old man with a shovel, we have a scary old woman with a ton of pigeons, and rather than protecting his home, Kevin must protect a good willed toy store by luring the bandits to his uncle's under renovation home, again thwarting them with destructive means.
The Cancer Research Institute, New York Medical College, Valhalla, N.Y.10595 Address Correspondence to: Dr. Z. DarzynkiewiczThe Cancer Research InstituteNew York Medical College100 Grasslands RoadElmsford, N.Y. 10523tel: 914-347-2801fax: 914-347-2804e-mail: darzynk@nymc.edu ABSTRACT. Two alternative modes of cell death can be distinguished,apoptosis and accidental cell death, generally defined as necrosis. Flowcytometry is the methodology of choice to study various aspects of celldeath including detection and quantitation of apoptotic or necrotic cells.It offers all the advantages of rapid, multiparameter analysis of largepopulations of individual cells to investigate the biological processesassociated with cell death. Numerous cytometric methods have been developedto identify apoptotic and necrotic cells which are widely used in variousdisciplines, in particular in oncology and immunology. The characteristicchanges in cell size, shape and morphology as well as in plasma membranestructure and transport function, function of cell organelles, in particularmitochondria, DNA stability to denaturation and endonucleolytic DNA degradationwhich occur during apoptosis, all are the features used to identify apoptoticand necrotic cells by cytometry. The principles of analytical methods todetect apoptosis or apoptosis based on these changes are described andthe methods are critically reviewed. Applicability of these methods bothin the research laboratory and in the clinical setting is discussed. Particularattention is focused on improper use of these methods and on data interpretation.Multiparameter analysis of various molecular and biochemical features ofthe dying cells as offered by flow cytometry opens new possibilities ininvestigation of molecular mechanisms in necrobiology. MODES OF CELL DEATHCell Necrobiology. Mechanisms associated with cell deathhave recently become a center of attention of researchers in a varietyof diverse fields, such as cell and molecular biology, oncology, immunology,embryology, endocrinology, hematology and neurology. Various aspects ofcell death including molecular, biochemical and morphological changes whichnot only occur in the dying cell but also predispose the cell to respondto an environmental or intrinsic signal by death, regulate the initialsteps leading to irreversible commitment to death and activate the post-mortemcell disposal machinery are the subject of intense studies (1-11). Becausethe scope of this field is already so extensive, involves many disciplines,and is directly correlated with a variety of life processes associatedwith cell cycle or differentiation, to define this field we have recentlyintroduced the term \"cell necrobiology\" (5). Cell necrobiology comprisesvarious modes of cell death, the biological changes which predispose, modulate,precede and accompany cell death, as well as the consequences and tissueresponse to the cell death. This term, which combines necros (death) andbios (life) may appear contradictory. The inconsistency, however, is moreapparent than real. Namely, in preparation for and in early stages of celldeath a complex cascade of biological processes, typical of cell life,takes place. These processes involve activation of many regulatory pathways,preservation and often modulation of transcriptional and translationalactivities, alteration of cell organelles activity, activation of manydiverse enzyme systems, modification of the cell plasma membrane structureand transport, etc. Of particular interest are changes in proteins whosefunction is to regulate the cells proclivity to apoptosis such as bcl-2(12-21) and ICE proteases (22-24) families of proteins. A term that refersto the biology of cell death, thus, is not a contradiction.Cell death culminates with irreversible cessation of biologicalactivity. It is often difficult to define at which point a cell has passedthe point of no return in the death process and which changes cannot bereversed. As an operational definition of cell death, independent of thetechniques measuring it, one may accept the passage of the cell throughsuch a point. Beyond such point, the passive degenerative post-mortem changestake placeApoptosis and Necrosis. Apoptosis and necrosis are twodistinct, mutually exclusive, modes of cell death (reviews, 1-11). Apoptosis,frequently referred to as \"programmed cell death\", is an active and physiologicalmode of cell death, in which the cell itself designs and executes the programof its own demise and subsequent body disposal. A multistep complex mechanismregulates the cell's propensity to respond to various stimuli by apoptosis,whose complexity has recently become apparent (12). The regulation systeminvolves the presence of at least two distinct checkpoints, one controlledby bcl- 2/bax family of proteins (13-17), another by the cysteine- (caspases)(22-24) and possibly by serine- (25-28) proteases. Through several oncogenes(e.g. c-myc) and tumor suppressor genes (e.g. p53), this system interactswith the machinery regulating cell proliferation and DNA repair. Regulatorymechanisms associated with apoptosis are the subject of recent reviews(9,12). Several review articles discuss antitumor strategies based on modulationof the cell's propensity to undergo apoptosis, a subject of great interestin oncology in recent years (6,29-33).A cell undergoing apoptosis activates a series of molecularand biochemical events which lead to its total physical disintegration.Because many of these changes are very characteristic and appear to beunique to apoptosis, they have become markers used to identify this modeof cell death biochemically, by microscopy or cytometry. One of the earlyevents is cell dehydration. Loss of intracellular water leads to condensationof the cytoplasm which results in a change in cell shape and size: theoriginally round cells may become elongated and generally, are smaller.Another change, perhaps the most characteristic feature of apoptosis, iscondensation of nuclear chromatin. The condensation starts at the nuclearperiphery and the condensed chromatin often takes on a concave shape resemblinga half-moon, horseshoe or sickle. The condensed chromatin has an uniform,smooth appearance, with no evidence of any texture normally seen in thenucleus. DNA in condensed (pycnotic) chromatin exhibits hyperchromasia,staining strongly with fluorescent or light absorbing dyes. The nuclearenvelope disintegrates, lamin proteins undergo proteolytic degradation,followed by nuclear fragmentation (karyorrhexis). Many nuclear fragments,which stain uniformly with DNA dyes and thereby resemble DNA droplets ofdifferent sizes, are scattered throughout the cytoplasm. The nuclear fragments,together with constituents of the cytoplasm (including intact organelles),are then packaged and enveloped by fragments of the plasma membrane. Thesestructures, called \"apoptotic bodies\", are then shed from the dying cell.When apoptosis occurs in vivo apoptotic bodies are phagocytized by neighboringcells, including those of epithelial or fibroblast origin (i.e.not necessarilyby \"professional\" macrophages), without triggering an inflammatory reactionin the tissue (reviews, 2,3,7,8,10,11).Activation of endonuclease(s) preferentially cleavingDNA between the nucleosomes is another characteristic event of apoptosis(1,3,11).The products of DNA degradation are nucleosomal and oligonucleosomalDNA fragments (180 bp and multiplicity of 180 bp) which generate a characteristic\"ladder\" pattern during agarose gel electrophoresis. Because the DNA inapoptotic cells is partially degraded, the fraction of low molecular weightDNA can be extracted whereas the nondegraded DNA remains in the cell (34).In many cell types, however, DNA degradation does not proceed to nucleosomalsized fragments but stops in generating 300 to 50 kb size DNA fragments(35).Another characteristic feature of apoptosis is the preservation,at least during the initial phase of cell death, of the structural integrityand most of the plasma membrane transport function. Also, cellular organelles,including mitochondria and lysosomes remain preserved during apoptosis.The mitochondrial transmembrane potential of mitochondria, however, ismarkedly decreased (36-39). Release of cytochrome c from mitochondria,believed to be modulated by bcl-2, appears to be one of the earliest eventsof apoptosis, triggering activity of caspases and other downstream apoptoticeffectors (18-21). Other features of apoptosis include mobilization ofintracellular ionized calcium (40), activation