Archie W. Prestayko

Low-Molecular-Weight Nuclear RNAs

[1, p. 285; 2-14]. Some RNAs smaller in size than these which contain dihydrouridine or dihydrothymidine have also been reported to be present in the nucleus, specifically in association with the chromatin fraction [15-20]. Although the functions of most of these LMWN RNAs are not defined, their specificity of localization in the nucleolus and the nuclear chromatin fraction along with the number of these molecules (which approximates that of the number of functional genes) has suggested they may have an initiating or structural role in gene readouts or a regulatory role in gene function [8, 10, 2123]. The recent findings which have indicated that some low-molecular-weight nucleolar RNAs have specific temporal associations with newly synthesized ribosomal precursors suggest the possibility that they may be involved in specific phases of synthesis or modification of the ribosomal precursors [24]. Number of low-molecular-weight nuclear RNAs.—In a search for a definite role for these molecules in cell function, one of the critical problems has been the clarification of the number of types of these RNA molecules. Although it is not yet possible to specify with precision the total number of low-molecular-weight RNA species in the various fractions of the nucleus, the minimal estimate is eleven (fig. 1), and the maximum is approximately forty-three [1, 25]. None of these values, however, exclude possible microheterogeneity of the various nuclear RNA species. Table 1 indicates that there are at least

IN VITRO INTERACTION OF COVALENTLY LINKED CLOSED CIRCULAR DNA WITH THE SECOND-GENERATION PLATINUM COMPOUNDS

Publisher Summary The binding of cis-diamminedichloroplatinum II (CDDP or cisplatin) to cellular DNA is the major mechanism of its antitumor activity. It has been proposed that CDDP causes intra- and interstrand crosslinks in DNA molecules by coordinate bonding of cis-diamminediaquoplatinum II, the solvated form of CDDP. The strong, nearly irrevisible binding is inhibited by chloride, cyanide, or other strong electron-donating ligands. Covalently closed circular DNAs have been used to investigate the interaction of CDDP with various DNA species. Using agarose gel electrophoretic and electronmicroscopic methods, it has been reported that CDDP induced conformational changes on superhelical covalently closed circular DNAs. The second-generation platinum analogs are categorized in two classes: platinum IV compounds that appear to break PM-2 DNA in vitro and platinum II compounds that produce conformational changes in supercoiled PM-2 DNA. The breakage of CCC PM-2 DNA is related to the trans-dihydroxy groups.

MORPHOLOGICAL MANIFESTATIONS OF CISPLATIN ANALOGS IN RATS: AN ULTRASTRUCTURAL STUDY

Publisher Summary The dose-limiting nephrotoxicity of cisplatin (cis-diamminedichloroplatinum II) presents a major problem in the treatment of various malignancies with this drug. Many analogs of cisplatin have been synthesized and tested for antitumor activity in experimental animal tumors. In addition to the investigations of the activity of these analogs, various animal toxicity models have been utilized to study the nephrotoxic and myelosuppressive potential of a number of the analogs. The primary action of cisplatin is on DNA resulting in the inhibition of DNA synthesis, the cytoarchitecture of the nuclei of cells are expected to be altered after treatment with cisplatin. Giant multinucleated sarcoma 180 cells have been observed in mice after treatment with cisplatin. These nuclei are in communication with each other by thin strands of nuclear material, and there are practically no cells in mitosis. Cytoplasmic organelles such as Golgi and mitochondria also show altered morphology. The chapter discusses the ultrastructural toxicity of cisplatin analogs on organ tissues including kidney, liver, spleen, and sciatic nerve of rats.

PREFACE TO VOLUME II

This second volume to the treatise Physics of Lakes is dedicated to a single topic, namely Lakes as Oscillators. There are several reasons why this topic plays such a prominent role. First, oscillations in lakes belong to those subjects, which were already studied by the pioneers in the seventeenth century. As Mortimer writes: “Readily observed, rhythmic fluctuations in lake level have long exercised a fascination and have stimulated mathematical modeling, but often with a longtime gap between observation and theoretical resolution [20]. The first detailed set of observations ([9], on Léman, 1730, introducing the local name ‘seiche’) and recognition of their occurrences in many lakes [26] were, it is interesting to note, preceded by systematic observations and conjectures by a Jesuit missionary [3] in 1671, describing the large but irregular ‘tides’ at the head of Green Bay (a gulf which opens onto Lake Michigan) and attributing to a combination of lunar tidal influence and to the main influence of the lake. Three centuries elapsed before those conjectures were confirmed by spectral analysis and numerical modelling [12, 13, 19]”, from [20]. Mortimer continues: “With early observations and conjectures as a prelude, physical limnology was launched as a distinct branch of geophysical fluid mechanics (L’ océanographie des lacs) by Forel’s lifetime study of Léman seiches and temperature regime [10]. But again, in one respect priority must go to Lake Michigan, i.e. to a US Army surveyor’s 1872 interpretation [8] of the conspicuous 2.2 h seiche at Milwaukee as a standing wave, thereby antedating Forel’s similar interpretation [11] by 3 years and providing yet another example of an original idea occurring to two persons at about the same time. Mathematical modelling of this seiche (as the first transverse mode [23]) confirmed the 1872 interpretation. In fact, hydrodynamic modelling may be said to have ‘cut its teeth’ on seiches : : :”, from [20]. Second, since the availability of electronic computation and the development of electronically based measuring techniques, which permitted relatively long term recording of detailed time series of density (via temperature and electrical conductivity) and velocity, the internal motion of the water in lakes became ‘observable’ via the construction of isotherm-depth or isopycnal time series at fixed mooring positions. Fast Fourier and more recently wavelet transforms and cross correlation analyses of such time series between synoptically recorded quantities became key working techniques to interpret whole-basin or localized internal processes. These