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Biomedical subjects

M A Napier

Publications and source records attributed to M A Napier.

30 records · Page 2Linked to original sources
PubMed1980

Requirement for reducing agents in deoxyribonucleic acid strand scisson by the purified chromophore of auromomycin.

By methanol extraction and high-pressure liquid chromatography a nonprotein chromophore has been obtained from the antitumor protein antibiotic auromomycin (AUR) which possesses the cytotoxic and the in vivo and in vitro deoxyribonucleic acid (DNA) strand scission activities of the parent material. The rate of DNA strand breakage by the purified chromophore is markedly stimulated by reducing compounds (maximally at approximately 0.1 mM dithiothreitol), but DNA strand scission activity is lost upon pretreatment of the chromophore with these agents. Apoprotein specifically protects against such inactivation but blocks the activity of both the stimulated and unstimulated reactions, presumably by complexing the chromophore and making it less available to the target DNA. Dithiothreitol-dependent scission of DNA by chromophore is faster and more complete at 0 degrees C than at 37 degrees C. The reaction at 0 degrees C is almost entirely dependent on the presence of a reducing compound. Although 2-mercapto-ethanol does not stimulate the reaction of either AUR or its chromophore at 37 degrees C, it has a significant stimulatory effect at 0 degrees C.

Anti-Bacterial Agents↗
PubMed1980

Roles of chromophore and apo-protein in neocarzinostatin action.

The methanol-extractable, nonprotein chromophore of the antitumor, protein antibiotic neocarzinostatin (NCS) has at least the full activity of the parent compound in inhibiting DNA synthesis and growth of HeLa cells and in causing DNA strand breaks in vivo and in vitro. In vitro DNA strand scission by the chromophore is markedly stimulated by 2-mercaptoethanol and is inhibited by guanidine hydrochloride and alpha-tocopherol. By high-pressure liquid chromatography, this activity has been localized to fractions eluting at greater than 90% methanol and having fluorescence emission at 420 nm (excitation at 340 nm). The apo-protein of NCS is inactive by itself but complexes with the chromophore so as to regulate its availability during the in vitro reaction. In DNA strand scission the chromophore acts rapidly at both 0 and 37 degrees C, whereas native and reconstituted NCS are inactive at 0 degrees C and slowly active at 37 degrees C. Complex formation with apo-NCS stabilizes the chromophore. Reconstitution of NCS (pI 3.3) from chromophore and apo-protein (pI 3.2) was shown by both activity studies and isoelectric focusing on polyacrylamide gels. "Pre-NCS," the biosynthetic precursor of NCS, is identical to apo-NCS in amino acid composition, spectral properties, isoelectric focusing on polyacryl-amide gels, and ability to complex with isolated chromophore to form material with all the properties of native NCS.

Antibiotics, Antineoplastic↗
PubMed1978

Effect of calcium on structure and function of a hyaluronic acid matrix: carbon-13 nuclear magnetic resonance analysis and the diffusional behavior of small solutes.

Natural-abundance (13)C NMR at 25.16 MHz has been used to study a 2.5% matrix of hyaluronic acid at various degrees of polymerization and at various ionic strengths. Peak assignment is facilitated by comparing proton-decoupled and off-resonance-decoupled spectra of a hyaluronidase-depolymerized matrix with spectra from relevant monosaccharides. In contrast to the spectrum following depolymerization, the spectrum for intact matrix has considerable broadening, particularly for peaks assigned to the N-acetylglucosamine moiety. This is most dramatic for the hydroxymethylene carbon. With the addition of Ca(2+) above 5 mM these broadened peaks narrow and approach the sharpness observed for the hyaluronidase digest. There is no shift in resonance peak positions. These changes are quantitatively less impressive if Na(+) is substituted for Ca(2+). The data suggest the existence of a considerable degree of order in regions of the matrix at physiological concentrations of Ca(2+). Within such a matrix the translational movement of lysine and glucose is enhanced relative to that in a matrix of agarose. Further addition of Ca(2+) abrogates not only matrix order, but the enhanced diffusivity as well.

Calcium↗
PubMedDate not supplied

Polyclonal hyperviscosity syndrome.

The clinical course of two patients who presented with polyclonal hyperviscosity syndrome is described. Polymerizing IgG rheumatoid factors were isolated from the serum of both patients. The presence of these polymers with their extraordinary rheologic properties was the principal determinant of the abnormal rheological properties of the plasma. Neither patient had a discrete rheumatic disease. In both, a lymphoproliferative syndrome was present with features suggestive of the "pseudolymphoma" of Sjögren's syndrome.

Blood Viscosity↗
PubMedDate not supplied

Renal and blood pressure responses to synthetic atrial natriuretic factor in spontaneously hypertensive rats.

Atrial natriuretic factor (ANF) is a potent natriuretic and vasorelaxant agent that also stimulates guanosine 3',5'-cyclic monophosphate (cGMP) excretion in normotensive animals. These properties suggest that ANF may be involved in the regulation of blood pressure. To test a pure preparation of ANF in both normotensive and hypertensive animals, a synthetic 26 amino acid peptide (sANF) contained within endogenous rat ANF was infused intravenously into conscious Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) at doses from 12 to 190 pmol/minute. Mean arterial pressure fell progressively as doses of sANF were increased until maximum responses of -41 +/- 5 mm Hg and -29 +/- 5 mm Hg were obtained during infusion of 95 pmol/minute sANF in SHR and WKY, respectively. Heart rate was not significantly affected in either group. At sANF doses of 12 to 50 pmol/minute, urinary electrolyte excretion rose in a dose-related fashion and was similar in WKY and SHR. At infusions of 95 to 190 pmol/minute, the diuretic and saluretic responses were diminished in the hypertensive animals. Only the 190 pmol/minute sANF dose significantly enhanced cGMP excretion in SHR (p less than 0.05); however, in WKY urinary cGMP excretion was elevated in a dose-related fashion. At the highest sANF dose, cGMP excretion was approximately 15 times that observed in the pretreatment urine. The differences in the renal and blood pressure responses to sANF in SHR and WKY suggest that the actions of endogenous ANF may be altered in hypertension.

Animals↗