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At least 901 records · Page 50Linked to original sources
PubMed2005

A-432411, a novel indolinone compound that disrupts spindle pole formation and inhibits human cancer cell growth.

Microtubules are among the most successful targets for anticancer therapies and for the development of new anticancer drugs. A-432411 is a novel small molecule that destabilizes microtubules at high concentration and disrupts normal spindle formation at low concentration. A-432411 is an indolinone that is structurally different from other known synthetic microtubule inhibitors. This compound is efficacious against a variety of human cancer cell lines including drug-resistant HCT-15 that overexpresses Pgp170. Biochemical studies show that A-432411 competes with the colchicine-binding site on tubulin and inhibits microtubule polymerization. Fluorescence-activated cell sorting analysis indicates that A-432411 causes G2-M arrest and induces apoptosis. Cells treated with A-432411 have increased level of phospho-histone H3 at Ser10 and decreased level of phospho-cdc2 at Tyr15. Concurrently, securin and cyclin B1 expression levels remain the same, indicating the activation of the spindle checkpoint. Immunocytochemistry and fluorescence microscopy experiments reveal that 1 micromol/L A-432411 destabilizes microtubules in cells. At 0.1 micromol/L, the compound disrupts normal spindle pole formation possibly through stabilization of microtubule dynamic. Both structural and cellular properties of A-432411 make it an attractive candidate for further development.

Antineoplastic Agents↗
PubMedDate not supplied

Nonlinear component of the electroretinogram recorded from the posterior pole of normal and highly myopic human eyes.

To extract the nonlinear component of the electroretinogram (ERG) from the posterior pole (pp) of the human ocular fundus and to evaluate the possibility of its clinical application, three types of stimulus modes - double-flash, single-flash, and delayed single-flash stimuli - were produced using a conventional electrophysiological system. A large hexagonal element was presented on a CRT monitor, and ppERGs were recorded from 14 normal eyes and 16 eyes of eight highly myopic patients. The nonlinear component of the ppERG was obtained by subtracting the single-flash ERG and delayed single-flash ERG responses from the double flash ERG response. Three peaks were commonly observed in the nonlinear component of ppERG, all of which were significantly depressed in patients with high myopia. ppERGs that can be obtained using a simple algorithm might be useful in clinical applications.

Adolescent↗
PubMed1980

Medulloepithelioma arising from the posterior pole.

In the right eye of a 2 1/2-year-old boy a markedly prominent tumor, arising from the posterior pole, was found. The clinical diagnosis was retinoblastoma and the eye was removed. Histologically, however, this appeared to be a medulloepithelioma originating in the optic disc and in the posterior retina: an extremely rare localization as these tumors usually originate in the ciliary region. The tumor mainly consisted of neuroectodermal elements in several degrees of differentiation giving the aspect of a benign (hamartomatous) embryonal brain tumor rather than those of a retinal tumor. Some aspects of the nomenclature are discussed.

Child, Preschool↗
PubMed1985

Transfer of label from 3H-glucose in Digitaria eriantha leaves to the rust fungus Puccinia digitariae Pole Evans.

Digitaria eriantha pentzii was fed 3H-glucose prior to inoculation with uredospores of Puccinia digitariae Pole Evans. Twenty-one hours after inoculation, uptake of label from 3H-glucose by the primary infection structures of P. digitariae was demonstrated employing autoradiography. These results indicate that an exchange of nutrients between host and pathogen occurs very early on in the infection process, during the formation of the primary infection structures. Despite contrary reports that obligate parasites receive no nutrition before establishment of haustoria, this study supports the work of Andrews (Can J Bot 53:1103, 1975), who demonstrated uptake of 3H-glucose label from lettuce cotyledons into the primary and secondary infection vesicles, appressoria, and germ tubes of Bremia lactucae.

Autoradiography↗
PubMed2003

Stone clearance in lower pole nephrolithiasis after extra corporeal shock wave lithotripsy - the controversy continues.

BACKGROUND: To determine factors influencing the clearance of fragments after extra-corporeal shock wave lithotripsy (ESWL) for lower pole calyceal (LPC) stones. METHODS: In the period between July 1998 and Oct 2001, 100 patients with isolated lower polar calyceal calculi or= 14 years, were included in the study. Intravenous urograms (IVU) were reviewed to define the LPC anatomy (width of the infundibulum and pelvicalyceal angle). Study end points i.e. stone free status; number of shock waves used and number of sessions were correlated with variables like LPC anatomy, body mass index and stone size. RESULTS: At three months follow up the clearance for stone size 90 degrees ) had stone clearance of 94 and 100% respectively. For the infundibular width of < 4 mm, the stone clearance was 93% were as for > 4 mm, it was 100%. For body mass index (BMI) less than and > 30 kg/m2, the stone clearance was 92 and 95% respectively. CONCLUSIONS: There is a trend towards more ESWL sessions and shock wave requirement in patients with acute pelvi-calyceal angle and narrow infundibulum but it is not statistically significant. Size (<or= 20 mm) and BMI has no relation with stone clearance. With modern lithotripter, stones up to 20 mm could primarily be treated by ESWL, irrespective of an un-favorable lower polar calyceal anatomy and body habitus.

Adolescent↗
PubMed2004

Germline stem cells in the Drosophila ovary descend from pole cells in the anterior region of the embryonic gonad.

A fundamental yet unexplored question in stem cell biology is how the fate of tissue stem cells is initially determined during development. In Drosophila, germline stem cells (GSCs) descend from a subset of primordial germ cells (PGCs) at the onset of oogenesis. GSC determination may occur at the onset of oogenesis when a subset of PGCs is induced to become GSCs by contacting niche cells. Alternatively, the GSC fate could be predetermined for a subset of PGCs before oogenesis, due to either their interaction with specific somatic cells in the embryonic/larval gonads, or their inherently heterogeneous potential in becoming GSCs, or both. Here, we show that anterior somatic cells in the embryonic gonad already differ from posterior somatic cells and are likely to be the precursors of niche cells in the adult ovary. Furthermore, only pole cells in the anterior half of the embryonic gonad give rise to the PGCs that frequently acquire contact with nascent niche cells in the late larval ovary. Eventually, only these contacting PGCs become GSCs, whereas non-contacting PGCs directly differentiate into cystoblasts. The strong preference of these 'anterior PGCs' towards contacting niche cells does not require DE-cadherin-mediated adhesion and is not correlated with either orientation or rate of their divisions. These data suggest that the GSC fate is predetermined before oogenesis. The predetermination probably involves soma/pole-cell interaction in the anterior half of the embryonic gonad, followed by an active homing mechanism during PGC proliferation to maintain the contact between the 'anterior PGCs' and anterior somatic cells.

Animals↗
PubMed1993

Induction of cardiac muscle differentiation in isolated animal pole explants of Xenopus laevis embryos.

We have isolated a cDNA fragment encoding a portion of the myosin heavy chain alpha-isoform (XMHC alpha) in the amphibian, Xenopus laevis. The XMHC alpha transcript is highly enriched in adult heart RNA and is expressed exclusively in embryonic heart tissue. It therefore provides a tissue-specific marker for cardiac muscle differentiation during early embryogenesis. Using an RNAase protection assay, we can detect the onset of cardiac muscle differentiation in an anterior, ventral region of tailbud embryos, many hours before the appearance of a beating heart. Whole-mount in situ RNA hybridisation indicates that expression of the XMHC alpha gene is restricted to the developing heart primordium. XMHC alpha gene expression can also be induced in isolated animal pole explants of blastulae by treatment with the growth factor, activin A. Induction is dose-dependent, requiring high doses of the growth factor compared with that required for myotomal (skeletal) muscle differentiation. In contrast, no XMHC alpha transcripts are detected in explants incubated with basic FGF, despite the induction of myotomal muscle differentiation. Activin-induced explants show a similar temporal pattern of XMHC alpha gene expression to that found in normal embryogenesis. Furthermore, cells expressing this gene appear clustered in one or two foci within fused explant aggregates, which often show regular, spontaneous contractions after several days in culture. These results show that terminal differentiation of cardiac muscle can occur in growth factor-induced explants and may be distinguished from skeletal muscle differentiation by the dose and nature of the inducing factor.

Activins↗
PubMed2002

Cytokinetic actomyosin ring formation and septation in fission yeast are dependent on the full recruitment of the polo-like kinase Plo1 to the spindle pole body and a functional spindle assembly checkpoint.

In dividing cells, the assembly and contraction of the cytokinetic actomyosin ring (CAR) is precisely coordinated with spindle formation and chromosome segregation. Despite having a cell wall, the fission yeast Schizosaccharomyces pombe forms a CAR reminiscent of the structure responsible for the cleavage of cells with flexible boundaries. We used the myo2-gc fission yeast strain in which the chromosomal copy of the type II myosin gene, myo2(+), is fused to the gene encoding green fluorescent protein (GFP) to investigate the dynamics of Myo2 recruitment to the cytokinetic actomyosin ring in living cells. Analysis of CAR formation in relation to spindle pole body (SPB) and centromere separation enabled us to pinpoint the timing of Myo2 recruitment into a stable CAR structure to the onset of anaphase A. Depolymerisation of actin with latrunculin B did not affect the timing of Myo2 accumulation at the cell equator (although Myo2 no longer formed a ring), whereas depolymerisation of microtubules with either thiabendazole (TBZ) or methyl 2-benzimidazolecarbamate (MBC) resulted in a delay of up to 90 minutes in CAR formation. Microtubule depolymerisation also delayed the localisation of other CAR components such as actin and Mid1/Dmf1. The delay of cytokinesis in response to loss of microtubule integrity was abolished in cells lacking the spindle assembly checkpoint protein Mad2 or containing non-functional Cdc16, a component of the fission yeast septation initiation network (SIN). The delay was also abolished in cells lacking Zfs1, a component of the previously described S. pombe cytokinesis checkpoint. Recruitment of the polo-related kinase, Plo1, a key regulator of CAR formation, to the SPBs was substantially reduced in TBZ in a Mad2-dependent manner. Loading of Cdc7, a component of the SIN and downstream of Plo1 in the cytokinesis pathway, onto the the SPBs was also delayed in TBZ to the same extent as CAR formation. We conclude that CAR formation is subject to regulation by the spindle assembly checkpoint via the loading of Plo1 onto the SPBs and the consequent activation of the SIN.

Actins↗
PubMed2005

Mcp6, a meiosis-specific coiled-coil protein of Schizosaccharomyces pombe, localizes to the spindle pole body and is required for horsetail movement and recombination.

We report here that a meiosis-specific gene of Schizosaccharomyces pombe denoted mcp6+ (meiotic coiled-coil protein) encodes a protein that is required for the horsetail movement of chromosomes at meiosis I. The mcp6+ gene is specifically transcribed during the horsetail phase. Green fluorescent protein (GFP)-tagged Mcp6 appears at the start of karyogamy, localizes to the spindle-pole body (SPB) and then disappears before chromosome segregation at meiosis I. In the mcp6Delta strain, the horsetail movement was either hampered (zygotic meiosis) or abolished (azygotic meiosis) and the pairing of homologous chromosomes was impaired. Accordingly, the allelic recombination rates of the mcp6Delta strain were only 10-40% of the wild-type rates. By contrast, the ectopic recombination rate of the mcp6Delta strain was twice the wild-type rate. This is probably caused by abnormal homologous pairing in mcp6Delta cells because of aberrant horsetail movement. Fluorescent microscopy indicates that SPB components such as Sad1, Kms1 and Spo15 localize normally in mcp6Delta cells. Because Taz1 and Swi6 also localized with Sad1 in mcp6Delta cells, Mcp6 is not required for telomere clustering. In a taz1Delta strain, which does not display telomere clustering, and the dhc1-d3 mutant, which lacks horsetail movement, Mcp6 localized with Sad1 normally. However, we observed abnormal astral microtubule organization in mcp6Delta cells. From these results, we conclude that Mcp6 is necessary for neither SPB organization nor telomere clustering, but is required for proper astral microtubule positioning to maintain horsetail movement.

Amino Acid Sequence↗
PubMed1997

Calmodulin localizes to the spindle pole body of Schizosaccharomyces pombe and performs an essential function in chromosome segregation.

The essential calmodulin genes in both Saccharomyces cerevisiae and Schizosaccharomyces pombe were precisely replaced with genes encoding fusions between calmodulin and the green fluorescent protein (GFP). In living budding yeast the GFP-calmodulin fusion protein (GFP-Cmd1p) localized simultaneously to sites of cell growth and to the spindle pole body (SPB), the yeast analog of the centrosome. Having demonstrated proper localization of GFP-calmodulin in budding yeast, we examined the localization of a fusion between GFP and calmodulin (GFP-Camlp) in fission yeast, where calmodulin had not been localized by any method. We find GFP-Camlp also localizes both to sites of polarized cell growth and to the fission yeast SPB. The localization of calmodulin to the SPB by GFP fusion was confirmed by indirect immunofluorescence. Antiserum to S. pombe calmodulin labeled the ends of the mitotic spindle stained with anti-tubulin antiserum. This pattern was identical to that seen using antiserum to Sad1p, a known SPB component. We then characterized the defects in a temperature-sensitive S. pombe calmodulin mutant. Mutant cam1-E14 cells synchronized in S phase completed DNA synthesis, but lost viability during transit of mitosis. Severe defects in chromosome segregation, including hypercondensation, fragmentation, and unequal allocation of chromosomal material were observed. Immunofluorescence analysis of tubulin revealed a population of cells containing either broken or mislocalized mitotic spindles, which were never observed in wild-type cells. Taken together with the subcellular localization of calmodulin, the observed spindle and chromosome segregation defects suggest that calmodulin performs an essential role during mitosis at the fission yeast SPB.

Calmodulin↗
PubMed1998

The Kar3p and Kip2p motors function antagonistically at the spindle poles to influence cytoplasmic microtubule numbers.

Microtubules provide the substrate for intracellular trafficking by association with molecular motors of the kinesin and dynein superfamilies. Motor proteins are generally thought to function as force generating units for transport of various cargoes along the microtubule polymer. Recent work suggests additional roles for motor proteins in changing the structure of the microtubule network itself. We report here that in the budding yeast Saccharomyces cerevisiae microtubule motors have antagonistic effects on microtubule numbers and lengths. As shown previously, loss of the Kar3p motor stimulates cytoplasmic microtubule growth while loss of Kip2p leads to a sharp reduction in cytoplasmic microtubule numbers. Loss of both the Kip2p and Kar3p motors together in the same cell produces an intermediate phenotype, suggesting that these two motors act in opposition to control cytoplasmic microtubule density. A Kip2p-GFP fusion from single gene expression is most concentrated at the spindle poles, as shown previously for an epitope tagged Kar3p-HA, suggesting both of these motors act from the minus ends of the microtubules to influence microtubule numbers.

Cell Division↗
PubMed1998

Orientation of snow buntings (Plectrophenax nivalis) close to the magnetic north pole

Orientation experiments were performed with first-year snow buntings (Plectrophenax nivalis) during their autumn migration in a natural near-vertical geomagnetic field approximately 400 km away from the magnetic north pole. Migratory orientation of snow buntings was recorded using two different techniques: orientation cage tests and free-flight release experiments. Experiments were performed under clear skies, as well as under natural and simulated complete overcast. Several experimental manipulations were performed including an artificial shift of the E-vector direction of polarized light, depolarization of incoming light and a 4 h slow clock-shift experiment. The amount of stored fat proved to be decisive for the directional selections of the buntings. Fat individuals generally chose southerly mean directions, whereas lean birds selected northerly headings. These directional selections seemed to be independent of experimental manipulations of the buntings' access to visual cues even in the local near-vertical magnetic field. Under clear skies, the buntings failed to respond to either a deflection of the E-vector direction of polarized light or an experimental depolarization of incoming skylight. When tested under natural as well as simulated overcast, the buntings were still able to select a meaningful mean direction according to their fat status. Similarly, the free-flight release test under complete overcast resulted in a well-defined southsoutheast direction, possibly influenced by the prevailing light northwest wind. Clock-shift experiments did not yield a conclusive result, but the failure of these birds to take off during the subsequent free-flight release test may indicate some unspecified confusion effect of the treatment.

Journal Article↗
PubMed1990

Solubilization of aster-forming proteins from yeast: possible constituents of spindle pole body and reconstitution of asters in vitro.

Spindle pole bodies (SPBs) attached to nuclei were isolated from Saccharomyces cerevisiae; they nucleated microtubules to form asters in vitro. This aster-forming activity was stable in 30% dimethylsulfoxide or 10% 2-propanol and could be solubilized with KCl. The KCl extract contained many protein components, which aggregated upon dialysis against a low concentration salt solution. When incubated with tubulin, the aggregates formed asters. Measurements of the elongation rates of the astral microtubules indicated that the microtubules were nucleated from the SPBs or from the aggregates reconstructed from the KCl extract by dialysis. The plus end was distal to the astral center, as in the case of the microtubule organizing center (MTOC) of mammalian cells. We suggest that the proteins extracted with KCl are responsible for microtubule nucleation in SPBs and that this SPB seems to have the same mechanism for microtubule nucleation as the MTOC in higher eukaryotes.

Cell Fractionation↗
PubMed2003

Relationship between increased horizontal condylar angle and resorption of the posterosuperior region of the lateral pole of the mandibular condyle in temporomandibular joint internal derangement.

OBJECTIVES: The purpose of this study was to analyse the relationship between horizontal condylar angle, temporomandibular joint (TMJ) disk displacement and resorption of the lateral pole of the mandibular condyle (RLC). METHODS: The study comprised 162 TMJs (81 patients). Disk displacement was assessed and the horizontal angle of the condyle was measured on axial MR images. RLC was assessed on oblique frontal projection plain radiographs. RESULTS: The horizontal angle was increased in joints with disk displacement without reduction (one-factor ANOVA and Scheffe's f-test, P<0.05). The angle was greater in joints with RLC than in the joints without RLC (Student's t-test, P<0.05). CONCLUSIONS: Results suggest that the horizontal condylar angle is increased in joints with disk displacement without reduction. A possible relationship exists between RLC and increased horizontal condylar angle.

Adolescent↗
PubMed1983

Serial section reconstruction of the neural poles of hair cells in the human organ of Corti. II. outer hair cells.

Study of the anatomy of the cochlea, and in particular the morphology of synaptic relationships between hair cells and cochlear neurons, is essential for elucidation of the mechanisms of transduction of mechanical acoustic signals into electrical neural events. Because considerable gaps remain in our understanding of the microscopic anatomy of these synapses, particularly in the human, a reconstruction of the neural pole of outer hair cells of the human organ of Corti was performed. The data are based on 577 serial sections from the basal turn and 368 sections from the middle turn. This provided complete data on 11 and partial data on 9 outer hair cells. Terminal size of afferent fibers on outer hair cells was much more uniform than that found at the base of inner hair cells. Only small bouton-like terminals were found. Branching of afferent fibers was also seen at the base of outer hair cells. Each outer hair cell received approximately two to eight afferent nerve terminals. Multiple synaptic contacts between a single afferent terminal and an outer hair cell were common. Junctional membrane specialization consisted of synapses, desmosomes, coated vesicles and arrays of microtubules and membrane cisternae. Specialization at synapses consisted of asymmetrical membrane thickening. At outer hair cells the presynaptic membrane was thicker than the postsynaptic membrane. At inner hair cells the converse was true. At outer hair cells 35% of synapses had presynaptic bodies, compared to 83% of synapses at inner hair cells. Reciprocal synapses, with both hair cell to neuron and neuron to hair cell polarities, were found only on outer hair cells. Vesiculated efferent terminals were common at the base of outer hair cells. Both axosomatic and axodendritic efferent synapses were found. In addition, the same efferent fibers were found to synapse both on an outer hair cell and on an afferent dendrite. One example of a probable dendro-dendritic synapse in the outer spiral bundle is presented.

Cochlear Nerve↗
PubMed2002

Space-bandwidth product enhancement of a monostatic, multiaperture infrared image upconversion ladar receiver incorporating periodically poled liNbO3.

We investigate the space-bandwidth product of a ladar system incorporating an upconversion receiver. After illuminating a target with an eye-safe beam, we direct the return into a piece of periodically poled LiNbO3 where it is upconverted into the visible spectrum and detected with a CCD camera. The theoretical and experimental transfer functions are then found. We show that the angular acceptance of the upconversion process severely limits the receiver field of regard for macroscopic coupling optics. This limitation is overcome with a pair of microlens arrays, and a 43% increase in the system's measured space-bandwidth product is demonstrated.

Journal Article↗
PubMed2002

Fe Boltzmann temperature lidar: design, error analysis, and initial results at the north and south poles.

The design, development, and first measurements of a novel mesospheric temperature lidar are described. The lidar technique employs mesospheric Fe as a fluorescence tracer and relies on the temperature dependence of the population difference of two closely spaced Fe transitions. The principal advantage of this technique is that robust solid-state broadband laser source(s) can be used that enables the lidar to be deployed at remote locations and aboard research aircraft. We describe the system design and present a detailed analysis of the measurement errors. Correlative temperature observations, made with the Colorado State University Na lidar at Fort Collins, Colorado, are also discussed. Last, we present the initial range-resolved temperature measurements in the mesosphere and lower thermosphere over both the North and the South Poles obtained with this system.

Journal Article↗