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Biomedical subjects

K J Miller

Publications and source records attributed to K J Miller.

98 records · Page 6Linked to original sources
PubMed1979

Frost-weathering on Mars: experimental evidence for peroxide formation.

A laboratory study of the interaction of H2O frost with samples of the minerals olivine (Mg,Fe)2SiO4 and pyroxene (Mg,Fe)SiO3 at -11 degrees C to -22 degrees C revealed that an acidic oxidant was produced. Exposure of the frost-treated minerals to liquie H2O produced a sudden drop in pH and resulted in the production of copious O2(g) (as much as approximately 10(20) molecules g-1). Exposure of frost-treated samples to 5 ml of 0.1M HCOONa solution resulted in the rapid oxidation of up to 43% of the formate to CO2(g). These reactions were qualitatively similar to the chemical activity observed during the active cycles of the Viking lander Gas Exchange and Labeled Release Biology experiments. Attempts to identify the oxidant by chemical indicators were inconclusive, but they tentatively suggested that chemisorbed hydrogen peroxide may have formed. The formation of chemisorbed peroxide could be explained as a byproduct of the chemical reduction of the mineral. The following model was proposed. H+ was incorporated into the mineral from surface frost. This would have left behind a residual of excess OH-(ads) (relative to surface H+). Electrons were then stripped from the surface OH-(ads) (due to the large repulsive potential between neighboring OH-(ads)) and incorporated into the crystal to restore charge balance and produce a chemical reduction of the mineral. The resultant surface hydroxyl radicals could then have combined to form the more stable chemisorbed hydrogen peroxide species. While the chemisorbed peroxide should be relatively stable at low temperatures, it should tend to decay to O(ads)+ H2O(g) at higher temperatures with an activation energy of greater than or approximately 34 kcal mole-1. This is consistent with the long-term storage and sterilization behavior of the Viking soil oxidants. It is possible that as little as 0.1--1% frost-weathered material in the martian soil could have produced the unusual chemical activity that occurred during the Viking Gas Exchange and Labeled Release experiments.

Chemical Phenomena↗
PubMed1975

The distribution of anionic sites on the surfaces of mitochondrial membranes. Visual probing with polycationic ferritin.

Polycationic ferritin, a multivalent ligand, was used as a visual probe to determine the distribution and density of anionic sites on the surfaces of rat liver mitochondrial membranes. Both the distribution of bound polycationic ferritin and the topography of the outer surface of the inner mitochondrial membrane were studied in depth by utilizing thin sections and critical-point dried, whole mount preparations for transmission electron microscopy and by scanning electron microscopy. Based on its relative affinity for polycationic ferritin, the surface of the inner membrane contains discrete regions of high density and low density anionic sites. Whereas the surface of the cristal membrane contains a low density of anionic sites, the surface of the inner boundary membrane contains patches of high density anionic sites. The high density anionic sites on the inner boundary membrane were found to persist as stable patches and did not dissociate or randomize freely when the membrane was converted osmotically to a spherical configuration. The observations suggest that the inner mitochondrial membrane is composed of two major regions of anionic macromolecular distinction. It is well-known that an intermembrane space exists between the two membranes of the intact mitochondrion; however, a number of contact sites occur between the two membranes. We determined that the outer membrane, partially disrupted by treatment with digitonin, remains attached to the inner membrane at these contact sites as inverted vesicles. Such attached vesicles show that the inner surface of the outer membrane contains anionic sites, but of decreased density, surrounding the contact sites. Thus, the intermembrane space in the intact mitochondrion may be maintained by electronegative surfaces of the two mitochondrial membranes. The distribution of anionic sites on the outer surface of the outer membrane is random. The nature and function of fixed anionic surface charges and membrane contact sites are discussed with regard to recent reports relating to calcium transport, protein assembly into mitochondrial membranes, and membrane fluidity.

Animals↗
PubMedDate not supplied

The binding of substituted cis-Pt(II)-diammines to duplex DNA.

The results of a study of the binding to DNA of substituted cis-Pt(II) diammines, (cis-DP) are presented. Computer modeling of a series of cis-Pt(NH2R)2(+2)--where R = H, CH3, cyclopropyl, cyclobutyl, and cyclopentyl--to N7(G) atoms of two adjacent intrastrand guanine bases in a square planar complex in a pentamer duplex of DNA were performed. The stability of the complexes is studied by calculating the relative conformational energy of the cis-DP-DNA complexes with molecular mechanics (MM) and the intrinsic binding energy, which is the relative binding energy for ligand replacement in the presence of the substituents R with quantum mechanics. In the model, the receptor site geometry and the conformation of the DNA is changed little in the accommodation of the series of monosubstituted diammines. These diammines bind to one family of DNA conformations, denoted as IC in a previous study, and this suggests that a common conformational feature in the DNA may exist to explain the smooth trend in activity. The slight increase in van der Waals energy resulting from an increasing number of atoms in the substituents is countered by a larger decrease in the ligand replacement energy as the substituent increases in size. This overall decrease in relative energy is consistent with the slight decrease in activity as the substituent size increases.

Binding Sites↗
PubMedDate not supplied

Theoretical studies of cis-Pt(II)-diammine binding to duplex DNA.

The binding of cis-Pt(II) diammine (cis-DP) to double-stranded DNA was studied with several kinked conformations that can accommodate the formation of a square planar complex. Molecular mechanics (MM) calculations were performed to optimize the molecular fit. These results were combined with quantum mechanical (QM) calculations to ascertain the relative energetics of ligand binding through water vs direct binding of the phosphate to the ammine and platinum, and to guide the selection of DNA conformations to model complex formation. Based on QM and MM calculations, models are proposed that may be characterized by several general features. A structure involving hydrogen bonding between each ammine and distinct adjacent phosphate groups, referred to as closed conformation (CC), has already been reported. This is also found in the crystal structure of small dimers. We report alternative conformations that may be important in platination of duplex DNA. They are characterized by an intermediate conformation (IC), involving hydrogen bonding between one ammine and phosphate group, and an open conformation (OC), without ammine phosphate hydrogen bonding. The IC and OC can be stabilized by water bridges in the space between the ammine and the phosphate groups. Sugar puckers alternate from the type C(2')-endo or C(1')-exo (S), to the type C(3')-endo or C(2')-exo (N), with intermediate types near O(1')-endo (O). In general, the sugar puckers alternate from S to N to S through the platinated region (3'-TpG*pG*p-5'), with the complexed strand exhibiting, (3')-S*-N*-S-(5') alternation, while the complementary strand shows either (3')-S*-N*-S-(5') or (3')-S*-N*-O-(5') alternation. In both the OC and IC, a hydrogen bond is found between the ammine and O4(T) on thymine (T) at the (3') end, adjacent to the complex site. There is a continuous range of backbone conformations through the platinated region which relate the OC to the IC. The models presented suggest that the dynamics of the binding of the cis-Pt(II)-diammines to adjacent N7(G) in double-stranded DNA may encompass several conformational possibilities, and that water bridges may play a roll in supporting open and intermediate conformations. Proton-proton distances are reported to assist in the experimental determination of conformations.

Cisplatin↗
PubMedDate not supplied

The co-dependency concept: does it offer a solution for the spouses of alcoholics?

The popularity of the co-dependency concept has grown rapidly in the alcoholism treatment field. At the same time, empirical findings gained through scientific research have raised questions concerning the validity of the concept. This paper discusses some of the problems that are created by the disease model of co-dependency and highlights some alternative views that may be more appropriate. It is argued that the field's understanding of the alcoholic/spouse relationship and its ability to help the spouse are limited unless other conceptualizations are seriously considered.

Alcoholism↗
PubMedDate not supplied

Identification of the diacylglycerol kinase structural gene of Rhizobium meliloti 1021.

The cyclic beta-1,2-glucans of Rhizobium may function during legume nodulation. These molecules may become highly substituted with phosphoglycerol moieties from the head group of phosphatidylglycerol; diglyceride is a by-product of this reaction (K. J. Miller, R. S. Gore, and A. J. Benesi, J. Bacteriol. 170:4569-4575, 1988). We recently reported that R. meliloti 1021 produces a diacylglycerol kinase (EC 2.7.1.107) activity that shares several properties with the diacylglycerol kinase enzyme of Escherichia coli (W. P. Hunt, R. S. Gore, K. J. Miller, Appl. Environ. Microbiol. 57:3645-3647, 1991). A primary function of this rhizobial enzyme is to recycle diglyceride generated during cyclic beta-1,2-glucan biosynthesis. In the present study, we report the cloning and initial characterization of a single-copy gene from R. meliloti 1021 that encodes a diacylglycerol kinase homolog; this homolog can complement a diacylglycerol kinase deficient strain of E. coli. The sequence of the rhizobial diacylglycerol kinase gene was predicted to encode a protein of 137 amino acids; this protein shares 32% identity with the E. coli enzyme. Analysis of hydropathy and the potential to form specific secondary structures indicated a common overall structure for the two enzymes. Because diglyceride metabolism and cyclic beta-1,2-glucan biosynthesis are metabolically linked, future studies with diacylglycerol kinase mutants of R. meliloti 1021 should further elucidate the roles of the cyclic beta-1,2-glucans in the Rhizobium-legume symbiosis.

Amino Acid Sequence↗