Pantothenic acid, coenzyme A, and human chronic ulcerative and granulomatous colitis

To investigate further an apparent relationship between chronic ulcerative and granulomatous colitis and pantothenic acid deficiency, colonic tissues obtained at the time of colectomy in 29 patients with these disorders were assayed for pantothenic acid and for coenzyme A (CoA) activity. For comparison, normal colonic tissues free of pathological lesions were obtained from 31 patients having colectomy for carcinoma or diverticulitis. Plasma, red blood cells, and colonic mucosa were assayed microbiologically for free and total pantothenic acid. The activity of CoA in colonic mucosa was determined by assaying the acetylation of sulfanilamide. Concentrations of free, bound, and total pantothenic acid in blood and in colonic mucosa did not differ between the two groups of patients. Bound pantothenic acid increased linearly with total pantothenic acid. Colonic mucosa concentrated free pantothenic acid to about 50 times the level of blood, and pantothenic acid in red cells was similar to the concentration in plasma. Compared to normal gut mucosa, CoA activity was markedly low in mucosa from patients with chronic ulcerative or granulomatous disease despite the presence of normal amounts of free and bound pantothenic acid. A block in the conversion of bound pantothenic acid to CoA in diseased mucosa is suggested.     

Water Quality Modeling of Lake Michigan and Consideration of the Anomalous Ice Cover of 1976–1977

An intensive survey of water quality parameters was conducted on Lake Michigan during 1976 and 1977. A dynamic phytoplankton simulation model (MICH1) was developed to investigate the observed field data and to use in forecasting lake responses to various phosphorus loading scenarios. The 1977 data indicated that the southern basin of Lake Michigan lost up to 3 μg P/ L compared to concentrations observed in 1976. In an attempt to simulate this rapid depletion of phosphorus, MICH1 required an implicit representation of suspected effects of an extensive ice cover observed during the winter of 1976–77. This included increasing the net apparent settling rate eight fold during ice cover. A total phosphorus model (TPM) was used in conjunction with MICH1 ;for forecasting. These forecasts indicate a steady-state total phosphorus concentration of 7 μg P/ L, given a target load recommended by the 1978 Water Quality Agreement. The projected time to obtain 95% of steady-state response to a load change was 7–14 years.     

The elastic cartilage in the normal rat epiglottis. I. Fine structure

Unilateral electrolytic lesions of the locus coeruleus in rats result in spontaneous ipsiversive rotation, which is then replaced by contraversive rotation. One week after lesioning, when spontaneous turning ceases, apomorphine and d-amphetamine elicit contraversive circling behaviour, which was not affected by noradrenergic receptor blockade but was abolished by dopamine receptor blockade. The drug-induced contraversive circling response was also reproduced by piribedil but not clonidine. Combined unilateral electrolytic locus coeruleus and substantia nigra lesions on the same side resulted in apomorphine- and d-amphetamine-induced ipsilateral rotational behaviour which was indistinguishable from that seen with substantia nigra lesions alone. In rats with unilateral locus coeruleus lesions, the dose of intrastriatally injected apomorphine required to produce circling was less on the lesioned than the non-lesioned side. Direct injection of noradrenaline into one substantia nigra caused contraversive circling. Direct injection of phenoxybenzamine into one substantia nigra followed by apomorphine caused ipsiversive circling. The results suggest that the circling behaviour seen after unilateral locus coeruleus lesions depends on an asymmetry of striatal dopamine receptor activity and are consistent with a proposed coeruleus-nigral noradrenergic pathway, which enhances impulse flow in the dopaminergic nigrostriatal system.     

A thermodynamic "vocabulary" for metal ion interactions in biological systems

This Account focuses on metal ion-ligand complexes of biological relevance and measurements of the bond dissociation energies (BDEs) of such species. These complexes yield thermochemistry that begins to provide a thermodynamic "vocabulary" for thinking quantitatively about the strength of interactions in biological systems. The method utilized is threshold collision-induced dissociation in a guided ion beam tandem mass spectrometer. Accurate determination of BDEs requires attention to many details of the experiments and data analysis, as outlined here. Trends in metal ion-ligand BDEs are examined as a function of the metal ion, ligand, and extent of ligation. We elucidate the importance of ion-dipole and ion-induced dipole interactions, chelation, conformation, tautomeric form, steric interactions, and electronic effects such as hybridization and promotion. Interactions of metal ions with nucleobases and amino acids are quantified and the effects of hydration on these values are explored for the amino acid systems. Although data limitations restrict the present discussion to monocations, the trends elucidated here should be relevant to multiply charged metal ions, for which data is forthcoming.     

Two- and three-dimensional van krevelen diagrams: a graphical analysis complementary to the kendrick mass plot for sorting elemental compositions of complex organic mixtures based on ultrahigh-resolution broadband fourier transform ion cyclotron resonance mass measurements

Ultrahigh-resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry has resolved and identified the elemental compositions of over 10000 organic constituents of coal and petroleum crude oil. A plot of Kendrick mass defect versus Kendrick nominal mass sorts compounds into homologous series according to compound class (i.e., numbers of N, O, and S heteroatoms), type (number of rings plus double bonds), and degree of alkylation (number of CH(2) groups), to yield unique elemental assignments from ultrahigh-resolution mass measurements in the 200-900 Da range. Interpretation of such a vast compilation requires a simple (preferably graphical) means to differentiate between complex organic mixtures of different origin or processing. In an extension of the recently revived van Krevelen plot, each elemental composition is projected onto two or three axes according to its H/C, O/C, and/or N/C atomic ratios. The H/C ratio separates compounds according to degree of saturation, whereas O/C or N/C ratios separate according to O and N classes. We show that the three-dimensional van Krevelen diagram can completely separate different classes in pyridine-extracted coal or petroleum samples and can also graphically distinguish fossil fuels according to their nature (coal vs petroleum), maturation (coals of different rank), and processing (the same coal at two stages of liquefaction). The van Krevelen diagram thus appears well suited to amplifying and exposing compositional differences within and between complex organic mixtures.     

Analysis of oil content of maize by wide-line NMR

A series of experiments to define feasibility, accuracy, and precision of wide-line nuclear magnetic resonance spectroscopy as a nondestructive analytical tool for the oil content of living seeds is described. Corn samples, ranging from single seeds to 25 g, were scanned by NMR and gravimetrically analyzed. A high positive correlation (r = 0.99⁺) was invariably encountered. Single, 30-sec NMR scans on 25-g corn samples gave estimates within ±33 ing of the “true” oil content 95% of the time. Error associated with single, 30-sec scans of individual corn kernels amounted to ±1.3 mg of oil at the same confidence level. Samples containing more than 4.5% moisture contribute to the NMR signal, and therefore oil content is overestimated. A new dimension is added to the breeding and genetics of oil crops by the application of the NMR technique in that the process is non-destructive and feasible even for single seeds. The usefulness of the technique in studies involving the nature of water and its surrounding medium is suggested.     

Adaptive resynthesis of O6-methylguanine-accepting protein can explain the differences between mammalian cells proficient and deficient in methyl excision repair

Mammalian cells have been classified as proficient (Mer(+)) or deficient (Mer(-)) in methyl excision repair in terms of their cytotoxic reactions to agents that form O(6)-alkylguanine and their abilities to reactivate alkylated adenoviruses. O(6)-Methylguanine (O(6)MeGua) is considered to be a lethal, mutagenic, and carcinogenic lesion. We measured the abilities of cell extracts to transfer the methyl group from an exogenous DNA containing O(6)MeGua to acceptor protein. The constitutive level of acceptor activity was independent of the Mer phenotype and was approximately 100,000 acceptor sites per cell. Treatment of cells with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) results in a dose-dependent decrease in the acceptor activity in extracts because the rapid reaction between endogenous O(6)MeGua and acceptor protein makes the latter unavailable for further reaction. Treatment of cells with 1 muM MNNG for 15 min or 2 muM for approximately 2 min uses up >95% of the constitutive activity. However, Mer(+) cells, which are resistant to MNNG, rapidly resynthesize new acceptor protein, and the activity returns to the basal level in approximately 90 min. In Mer(-) tumor cells and Chinese hamster cells, which are sensitive to MNNG, resynthesis is not detectable in 90 min. Mer(-) simian virus 40-transformed fibroblasts, known to have an intermediate sensitivity to MNNG, have an intermediate resynthesis rate. Treatment of cells with multiple low doses of MNNG results in the enhanced production of O(6)MeGua-accepting protein in levels 2.5-fold above the constitutive values for Mer(+) tumor cells and to approximately 1.5-fold for Mer(+) fibroblasts or Mer(-) simian virus 40-transformed cells. Such treatments reduce the activities in Mer(-) tumor cells and Chinese hamster cells. We conclude: (i) estimates of O(6)MeGua in cellular DNA shortly after treatment may be seriously in error because of the rapid repair of this lesion, and (ii) the adaptive resynthesis of acceptor protein, not its constitutive level, is the important correlate of cell resistance to methylating agents.