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Biomedical subjects

C E Brown

Publications and source records attributed to C E Brown.

At least 109 records · Page 6Linked to original sources

Puerperal pelvic thrombophlebitis: impact on diagnosis and treatment using x-ray computed tomography and magnetic resonance imaging.

The clinical diagnosis of puerperal pelvic thrombophlebitis was confirmed by x-ray computed tomography in 11 women, and further documented in six by magnetic resonance imaging. Venous thrombi were demonstrated in ovarian, iliofemoral, and inferior vena caval vessels. In six women with ovarian vein involvement and no evidence of iliofemoral thrombophlebitis, resolution followed intravenous antimicrobial therapy alone, and in three of these, resolution was confirmed by x-ray tomography. In contrast, three of five women with symptomatic iliofemoral thrombophlebitis had a prolonged febrile course despite antimicrobial and heparin therapy. The clinical courses of these 11 women were consistent with the observation that pelvic thrombophlebitis is associated with pelvic infection. Disease manifested within a few days after parturition was more likely due to ovarian vein involvement, whereas disease with later onset of symptoms was more likely due to iliofemoral thrombosis, with or without vena caval extension. Through the use of x-ray computed tomography and magnetic resonance imaging, the natural course of pelvic thrombophlebitis can be better elucidated and therapeutic regimens more clearly evaluated.

Female↗

The effect of pH on the interaction of substrates and effector to yeast and rabbit muscle pyruvate kinase.

The interaction of fructose 1,6-bisphosphate, phosphoenolpyruvate and ADP with pyruvate kinase (ATP: pyruvate 2-O-phosphotransferase, EC 2.7.1.40) from yeast and rabbit muscle has been studied as a function of pH utilizing the quenching of protein fluorescence at 330 nm by these ligands. Both the muscle and the yeast pyruvate kinase interact with either ADP or phosphoenolpyruvate with similar affinity, indicating that the substrate-binding sites for these two isozymes are similar. The major difference between the yeast and muscle isozymes is their affinity with fructose 1,6-bisphosphate. Fructose 1,6-bisphosphate interacts with the yeast isozyme in orders of magnitude more strongly than with the muscle isozyme. Moreover, the affinity of fructose 1,6-bisphosphate to the yeast isozyme is strongly pH-dependent, while the interaction of fructose 1,6-bisphosphate with the muscle isozyme is independent of pH. The data indicate that yeast pyruvate kinase undergoes a conformational change as the pH is increased from 6.0 to 8.5.

Adenosine Diphosphate↗

Analgesic potencies of morphine 3- and 6-sulfates after intracerebroventricular administration in mice: relationship to structural characteristics defined by mass spectrometry and nuclear magnetic resonance.

Morphine 3-sulfate, which carries a polar, acidic group at the 3-position much like morphine, does not differ greatly in analgesic potency from morphine following intracerebroventricular administration. This differs from the non-ionizable 3-methyl and 3-ethyl ethers, which are less potent analgesics than morphine. Morphine 6-sulfate, which differs from morphine by having an ionizable group at carbon-6 at physiological pH, is a more potent analgesic than morphine following intracerebroventricular administration. Variations in analgesic potency following modifications at the hydroxyl groups appear only to reflect alterations in point charges rather than structural alterations.

Analgesics↗

Response of tissue phosphate content to acute dietary phosphate deprivation in the X-linked hypophosphatemic mouse.

In order to evaluate a possible role for tissue phosphate or phosphorylated compounds in mediating the increase in plasma 1,25(OH)2D3 levels during dietary phosphate deprivation, renal cortical phosphate content has been measured in both normal and X-linked hypophosphatemic mice on a normal diet and also after acute dietary phosphate deprivation. We find that the metabolism of inorganic phosphate and phosphorylated organic compounds in the renal cortex of Hyp mice is not altered in response to their very low levels of serum phosphate. Skeletal muscle does not lose inorganic phosphate and/or phosphorylated metabolites to compensate for drastic loses of serum phosphate during acute dietary deprivation in either normal or Hyp mice. Furthermore, the chronic low level of serum phosphate and altered hormonal regulation in Hyp mice do not produce alterations in mineral composition of the bone with the possible exception that the stoichiometry of the apatite might be slightly different.

Animals↗

Cross-polarization/magic-angle sample-spinning C NMR spectroscopic study of chlorophyll a in the solid state.

Solid-state cross-polarization/magic-angle sample-spinning (13)C NMR spectra have been recorded on chlorophyll a-water aggregates, methyl pyrochlorophyllide a, and methyl pyropheophorbide a (derivatives that lack a phytyl chain). Spectra have also been collected under a decoupling regime in which resonances of certain hydrogen-bearing carbon atoms are suppressed. These observations are used to assign the solid-state spectra.

Journal Article↗

Regulation of plasma 1,25-(OH)2-D3 by phosphate: evidence against a role for total or acid-soluble renal phosphate content.

In order to evaluate a possible role for tissue phosphate or phosphorylated compounds in mediating the increase in plasma 1,25-(OH)2-D3 levels during dietary phosphate deprivation, measurements of total and acid-soluble renal cortical phosphate content have been made in both intact and hypophysectomized (hypox) rats eating a normal diet and also after four days of dietary phosphate deprivation. Similar measurements were also made in phosphate-deprived hypophysectomized rats replaced with growth hormone (GH). Total and acid-soluble renal cortical phosphate content averaged 81 +/- 8 mumol/g and 4.1 +/- 0.6 mumol/g, respectively, in intact rats eating the normal diet and were not significantly altered after phosphate deprivation despite a fall in plasma phosphate of about 40% and a fourfold increase in plasma 1,25-(OH)2-D3 levels. Total and acid-soluble renal cortical phosphate content levels were higher in hypox rats, averaging 92 +/- 8 mumol/g and 4.9 +/- 0.7 mumol/g, respectively, but also did not change after phosphate deprivation. Replacement of phosphate-deprived hypox rats with GH resulted in a further fall in plasma phosphate and a significant increase in plasma 1,25-(OH)2-D3 levels, but there was no change in either total or acid-soluble renal cortical phosphate content. The distribution of organophosphorus compounds in the acid-soluble phosphate fraction in these experiments was also evaluated using 31P NMR spectrometry. Although there appeared to be an increase in the total concentration of organophosphorus compounds after phosphate deprivation, this effect was not altered by hypophysectomy or by replacement of phosphate-deprived hypox rats with GH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Changes in 25-hydroxyvitamin D3 alpha- and 24-hydroxylase activities of kidney cells isolated from rats with either unilateral kidney damage or acute renal insufficiency.

25-Hydroxyvitamin D3 1 alpha- and 24-hydroxylase, NADPH-cytochrome c reductase, heme oxygenase, and ATPase activities were studied in viable kidney cells isolated from rats submitted to unilateral kidney damage (cortical electrocoagulation) and during the development of acute renal failure subsequent to excision of the contralateral undamaged kidney. Measurements of blood pH, plasma total and ionized calcium, phosphorus, creatinine, kidney histology, and phosphorus nuclear magnetic resonance spectroscopy determinations of phosphorus-containing compounds in kidney tissue were also performed. Seventy-two hours after unilateral kidney damage, no significant changes were observed in blood pH or in the plasma parameters studied. During this period, a significant increase in the activity of the 25-hydroxyvitamin D3 hydroxylases could be demonstrated in the cells of the contralateral undamaged kidney. A similar pattern of compensatory rise in the activity of the other enzymes studied was not detected. However, in the damaged kidney viable cells, the hydroxylase activities remained unchanged relative to those in sham-operated controls, despite a 5-fold increase in the inorganic phosphate content and a marked decrease in the organophosphorus and ATP content of this tissue. During the development of acute renal failure, a significant decrease in the activity of the hydroxylases occurred only when the rise in plasma creatinine concentration suggested severe renal insufficiency.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

Characterization of the solid components of biological tissues by cross-polarization, magic angle NMR spectrometry.

A biological tissue is composed of cytosol, which can be investigated by high resolution nuclear magnetic resonance (NMR) spectroscopy, and membrane and particulate components, which yield NMR spectra similar to those of solids. In this review, the theoretical and technical requirements of recording NMR spectra of solids with cross polarization and magic angle sample spinning techniques are compared with the physical characteristics of the solid components of biological tissues. Current applications of cross-polarization, magic angle NMR spectroscopy to the investigation of membranes, mineral deposits and biosynthetic pathways are presented and discussed in terms of the biomedical questions to which this technique might be applied.

Amino Acids↗

Measurement of ligand binding with nuclear magnetic resonance spectroscopy.

A method is described for measuring with nuclear magnetic resonance (NMR) spectroscopy the binding of ligands to particulate components of cells. This method is sensitive to intermediate-strength binding, which is difficult to measure with standard radiotracer binding assays, and is insensitive to 'tight' binding. Nonspecific binding and entrapment can be distinguished from specific binding even when a pharmacological agent is not available for competitive binding assays. Thus, the experimental approach presented provides a means of studying the possible physiological roles in neural tissue of metabolites that have not been implicated by neuropharmacological and neurophysiological experiments. The utility of this technique is discussed in terms of the information it has provided about the binding of enkephalin, epinephrine, acetylcholine and carnosine. This technique, although it uses technology new to most neuroscience laboratories, should be relatively easy to apply to existing research topics. The NMR spectrometer required for the binding assay is the type already found on most academic campuses, and the ligand need not have any special isotopic label. The particulate fraction can be prepared in the same way as for the radiotracer binding assays, which means that both tight and intermediate-strength ligand binding can be measured with the same preparation.

Binding Sites↗

Interactions among iron(II) bleomycin, Lewis bases, and DNA.

The interaction of sulfur-containing ligands with complexes of Fe(II) bleomycin [Fe(II)Blm] was investigated by comparing DNA strand-scission activity with the structural characteristics of the complex. The bithiazole ring of excess Blm can form intermolecular complexes with Fe(II)Blm and with NO-Fe(II)Blm, and the bithiazole groups of CO-Fe(II)Blm interact with the metal center. This binding can be reversed by glutathione, CO-Fe(II)Blm binds to poly(dA-dT) . poly(dA-dT) via its bithiazole group to change the environment of the Fe2+ ion. Glutathione binds to the CO-Fe(II)Blm-poly(dA-dT) . poly(dA-dT) complex under conditions in which it stimulates DNA strand scission by Fe(II)Blm.

Bleomycin↗

Mesothelioma relative to asbestos, radiation, and methylcholanthrene.

The carcinogenicity of chrysotile asbestos fibers (Canadian and Rhodesian) for the mesothelium of pleura and peritoneum of NEDH rats was explored by injection of 2 mg of asbestos fibers suspended in saline intratracheally, intrapleurally, or intraperitoneally, with or without ancillary radiation treatment (1,000 rad to the whole body of parabiont rats or 2,000 rad to the right thorax of single rats), or alternatively, by injection of asbestos plus 1 mg of 3-methylcholanthrene. A highly significant incidence of mesothelioma (3.8%) was noted in 159 rats treated with asbestos alone, as compared with 0.1% in 1,417 control rats. Additional treatment with radiation or 3-methylcholanthrene increased this incidence to 11.8% and 25.5%, respectively, the latter increase alone being significant at the .01 level of probability.

Animals↗

Enzymatic and immunological evidence for two forms of carnosinase in the mouse.

Carnosinase (aminoacyl-L-histidine hydrolase, EC 3.4.13.3) hydrolyzes the dipeptide carnosine (beta-alanyl-L-histidine), which is thought to play a role in cerebral and skeletal muscular function and has been implicated as a neuroaffector in the olfactory bulb. Carnosinase activity is present in many tissues of the mouse including heart, liver and lung, but it is most active in kidney, uterus and nasal olfactory mucosa. Kinetic measurements with 1H-NMR spectroscopy indicate that the enzyme is stereospecific and can hydrolyze L-but not D-carnosine. Anserine is a poorer substrate, while homocarnosine is essentially a non-substrate. However, these two dipeptides are effective inhibitors of the hydrolysis of L-carnosine. Carnosinase activity is unaffected when assayed in 2H2O at 99% isotopic purity. From considerations of the effect of Mn2+ on (1) substrate concentration velocity curves; (2) thermostability, and (3) inhibitor behavior, tissues with carnosinase can be divided into two groups. Kidney, uterus and olfactory mucosa represent one group, while central nervous system, muscle, spleen, etc. represent the second. The validity of this classification is confirmed by immunological evidence. Antiserum prepared against carnosinase purified from kidney cross-reacts with and inhibits the activity of olfactory mucosa, kidney and uterus but not that from central nervous system, heart or liver.

Animals↗