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Biomedical subjects

D Brill

Publications and source records attributed to D Brill.

14 recordsLinked to original sources
PubMed2001

Cytotoxic mechanism of XK469: resistance of topoisomerase IIbeta knockout cells and inhibition of topoisomerase I.

Topoisomerase IIbeta knockout mouse cells (beta-/-) were found to have only slight resistance to m-AMSA, a dual topoisomerase IIalpha-IIbeta poison, as compared to wild-type cells (beta+/+) during 1 h or 3 day exposures to the drug. In contrast, the beta-/- cells were greater than threefold resistant to XK469, a selective topoisomerase IIbeta poison during three day drug exposures (beta+/+ IC(50) = 175 microM, beta-/- IC(50) = 581 microM). Short term (1 h) exposure to XK469 was not cytotoxic to either beta-/- or beta+/+ cells, suggesting that anticancer therapy with XK469 may be more efficacious if systemic levels can be prolonged. During studies on topoisomerase activity in nuclear extracts of the beta+/+ and beta-/- cells, we found evidence that XK469 is a weak topoisomerase I catalytic inhibitor. The high IC(50) for topoisomerase I inhibition (2 mM) suggests that topoisomerase I is not a significant target for XK469 cytotoxicity.

Animals↗
PubMed2000

Emission pattern of high-energy pions: A new probe for the early phase of heavy-Ion collisions

The emission pattern of charged pions has been measured in Au+Au collisions at 1 GeV/nucleon incident energy. In peripheral collisions and at target rapidities, high-energy pions are emitted preferentially towards the target spectator matter. In contrast, low-energy pions are emitted predominantly in the opposite direction. The corresponding azimuthal anisotropy is explained by the interaction of pions with projectile and target spectator matter. This interaction with the spectator matter causes an effective shadowing which varies with time during the reaction. Our observations show that high-energy pions stem from the early stage of the collision whereas low-energy pions freeze out later.

Journal Article↗
PubMed1998

Signal processing of the echo signatures returned by submerged shells insonified by dolphin "clicks:" active classification.

A large set of dolphin-emitted acoustic pulses ("echolocation clicks") have been examined, which were reflected from various elastic shells that were suspended, underwater, 4.5 m in front of the animal in a large test site in Kaneohe Bay, Hawaii. A carefully instrumented analog-to-digital system continuously captured the emitted clicks and also the returned, backscattered echoes (A/D conversion at 500 kHz). Using standard conditioning techniques and food reinforces, the dolphin is taught to push an underwater paddle when the "correct" target-the one he has been trained to identify-is presented to him. He communicates his consistently correct identifying choices in this manner. Many echoes returned by three types of cylindrical shells in both the time and frequency domains as well as in the joint time-frequency (t-f) domain, by means of Wigner-type distributions have been examined. It will be shown exactly how specific features observable in these displays are directly related to the physical characteristics of the shells. This processing takes advantage of certain fundamental resonance principles to show which echo features contain information about the size, shape, wall thickness, and material composition of both the shell and its filler substance. In the same fashion that these resonance features give the identifying characteristics of each shell, it is believed they may also give them to the dolphin. These echo features may allow him to extract the target properties by inspection without any need for computations. It is claimed that this may be the fundamental physical explanation of the dolphin's amazing target ID feats, upon which they base their recognition choices. This claim may be substantiated by the detailed analysis of many typical echoes returned by various shells, when they are interrogated by several dolphins. Thus far, this analysis of many echoes from many shells has only been carried out for a single dolphin.

Animals↗
PubMed1989

DNA replication and cell cycle control in Xenopus egg extracts.

Aspects of the regulation of DNA replication and mitosis have been studied using a cell-free extract of Xenopus eggs. The extract is characterized by repeated cycles of DNA replication and mitosis, which are accompanied by periodic synthesis and degradation of cyclins as well as fluctuations in the level of Histone H1 kinase activity. DNA replication in this system is dependent upon the formation of a nucleus. However, while nuclear structures are clearly required for initiation, a complete nuclear membrane does not appear to be necessary. Indirect immunofluorescence and DIC microscopy indicate that nuclear reformation from chromosomes occurs asynchronously around individual chromatids. Lamin polymerization, biotin-11-dUTP incorporation and association of polymerases with chromatin occur before membrane formation is complete. S phase nuclei are typified by the co-distribution of both anti-DNA polymerase alpha and anti-PCNA antibodies as discrete spots of fluorescence which align the chromatin. However, as DNA replication is terminated, PCNA fluorescence fades and DNA polymerase alpha dissociates from the chromatin and is redistributed throughout the nucleoplasm. By inhibiting DNA replication with aphidicolin, both DNA polymerase alpha and PCNA remain associated with the chromatin throughout prolonged incubation. Under these conditions mitosis is delayed by up to 70 min, although both the general rate of protein synthesis and more importantly the rate of cyclin synthesis and histone kinase activation are unaffected. Upon nuclear envelope breakdown and lamin dispersal, cyclins degrade; however, no chromosomes are formed, and both PCNA and DNA polymerase alpha remain associated with the chromatin. Also, histone kinase activity is maintained at elevated levels.

Animals↗
PubMed1987

DNA repair in human promyelocytic cell line, HL-60.

The human promyelocytic cell line, HL-60, shows large changes in endogenous poly(ADP-ribose) and in nuclear ADP-ribosyl transferase activity (ADPRT) during its induced myelocytic differentiation. DNA strand-breaks are an essential activator for this enzyme; and transient DNA strand breaks occur during the myelocytic differentiation of HL-60 cells. We have tested the hypothesis that these post-mitotic, terminally differentiating cells are less efficient in DNA repair, and specifically in DNA strand rejoining, than their proliferating precursor cells. We have found that this hypothesis is not tenable. We observe that there is no detectable reduction in the efficiency of DNA excision repair after exposure to either dimethyl sulphate or gamma-irradiation in HL-60 cells induced to differentiate by dimethyl sulphoxide. Moreover, the efficient excision repair of either dimethyl sulphate or gamma-irradiation induced lesions, both in the differentiated and undifferentiated HL-60 cells, is blocked by the inhibition of ADPRT activity.

Cell Differentiation↗
PubMed1983

Radionuclide cerebral imaging confirming brain death.

Cerebral blood flow (CBF) was measured by portable radionuclide cerebral imaging (RCI) and by four-vessel cerebral contrast arteriography in 15 clinically brain-dead patients, including six children. Neither technique showed evidence of CBF, although four RCI scans showed sagittal sinus activity. Portable scanning techniques are therefore considered valid determinants of brain death and may be useful in lieu of contrast cerebral arteriography.

Adolescent↗
PubMed1980

Drosophila nuclei replicate in Xenopus eggs.

Nuclei isolated from a permanent cell line derived from Drosophila melanogaster embryos have been injected, along with a radioactive DNA precursor [3H]TTP, into Xenopus laevis eggs. In culture, less than 7% of the cells were in S phase. After a 90 min incubation, following injection into eggs, 99% of the nuclei were shown by autoradiography to have synthesized DNA. In a similar experiment, a density label BrdUTP was injected into eggs along with the nuclei. Subsequent analysis on caesium chloride gradients showed that this DNA synthesis was semi-conservative replication. Therefore we conclude that signals present in Xenopus egg cytoplasm can initiate and sustain true semi-conservative DNA replication in nuclei from an invertebrate organism.

Animals↗