Biomedical subjects
L R Brown
Publications and source records attributed to L R Brown.
Hippel-Lindau syndrome.
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Ataxia-telangiectasia (Louis-Bar syndrome).
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The role of lysine-41 in ribonuclease A studied by proton-magnetic-resonance spectroscopy of guanidinated ribonuclease A.
Ribonuclease A has been guanidinated at the lysine residues and the nona-guanidinated and deca-guanidinated (fully substituted) products separated. In confirmation of an earlier report by Glick and Barnard (1970), it has been shown by chemical procedures that the former derivative is not reacted at lysine-41. Guanidination of lysine-41 to produce the fully substituted product causes loss of enzymic activity without any apparent change of conformation, as tested by conformational comparisons (using proton magnetic resonance spectroscopy) including (a) difference spectroscopy, evidence for the involvement of lysine-41 in a catalytic role in the enzyme. Dimethylation of lysine-41 of nona-guanidinated ribonuclease A produces sharp proton resonances which shifts as the dimethylamino group is titrated and allow the determination of an apparent pK of 8.8 for unsubstituted lysine-41.
Cleavage of lambda DNA by a site-specific endonuclease from Serratia marcescens.
Three sites recognized by SmaI endonuclease, purified from Serratia marcescens SB, have been located on lambda DNA at 0.406, 0.656, and 0.825 fractional lengths from the left end of the DNA molecule.
Effect of Skylab missions on clinical and microbiologic aspects of oral health.
Clinical and microbiologic measures of oral health were assessed in all crew members of each Skylab mission. Clinical factors included preflight and postflight clinical services, provisions for in-flight emergency dental care, and the preflight and postflight monitoring of alterations in clinical indexes of oral health. Microbiologic measures included the preflight and postflight monitoring of changes in microbial populations at various intraoral sites. Problems involving preflight and postflight clinical services were minimal and easily resolved. In-flight dental problems requiring emergency self-treatment were not encountered. Moderate increases were observed in the in-flight increments of dental plaque, calcalus, and gingival inflammation. With the possible exception of gingival inflammation, mission-related changes in clinical indexes of oral health mainly corresponded to those of comparable periods under more conventional circumstances. Microbiologic assessments showed noteworthy elevations in counts of specific anaerobic components of the oral microflora, streptococci, neisseria, lactobacilli, and enteric bacilli. Since most microbial changes occurred after the preflight incorporation of the space diet, they were believed to be diet related. The most meaningful finding of the study was the relative absence of intraoral changes that are hazardous to one's health.
Twenty-two dimensions of the population problem.
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55 degrees oblique hilar tomography.
Fifty-five-degree oblique hilar tomography is an accurate and simple means of evaluating hilar anatomy and pathology. It is of most value in proving the hilum to be normal in cases in which plain chest roentgenograms suggest a hilar lesion. It is accurate in differentiating hilar adenopathy from hilar masses and in both of these it is helpful in determining the extent and bilaterality of the disease process. Unfortunately, granulomatous infiltrates within the hilum cannot be differentiated from tumor. The procedure is of limited value in the presence of diffuse perihilar pulmonary fibrosis, and at this time caution must be advised in the interpretation of small, unilateral, ill-defined hilar densities as tumors.
Evaluation of the pulmonary hila by tomography.
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Comparison of membrane organization in mitochondria from yeast and rat liver by nuclear magnetic resonance spectroscopy.
Proton magnetic resonance (PMR) and carbon-13 magnetic resonance (CMR) spectra of intact, unsonicated yeast and rat liver motochondria show differences which may be correlated with the composition of the membranes. High resolution PMR and CMR signals in intact yeast mitochondria have been assigned to regions of fluid lipid-lipid interaction on the basis of spectra of extracted lipid and protein, and the temperature dependence of NMR signals from the intact membrane. PMR spectra suggest that about 20% of total yeast phospholipid is in regions where both intramolecular fatty acid chain mobility and lateral diffusion of entire phospholipid molecules are possible. No such regions apear to exist in rat liver mitochondria. For both yeast and rat liver mitochondria, comparison of PMR and CMR spectra suggests that about 50% of phospholipid appears to be in regions where intramolecular fatty acid chain motion is considerable, but lateral diffusion is restricted. The remaining phospholipid appears to have little inter- or intramolecular mobility. Since NMR observation of lipid extracts from membranes indicates that phospholipid-sterol interactions do not account for the spectra of intact mitochondria, these effects are interpreted in terms of extensive lipid-protein interactions.
Proton magnetic resonance spectroscopy of promitochondrial membranes from yeast grown under different regimes of lipid supplementation.
Promitochondrial membranes, prepared from Saccharomyces cerevisiae grown anaerobically under different conditions of lipid supplementation, have been examined by PMR spectroscopy. Promitochondria from cells cultured anaerobically in media containing both unsaturated fatty acid and sterol supplements, or containing unsaturated fatty acid alone, yield high resolution spectra similar to those which are characteristic of aerobic mitochondria. By contrast, promitochondrial membranes from cells grown only with sterol supplementation in order to deplete unsaturated fatty acid and total phospholipid content of the organelles, yielded PMR spectra which were very substantially broadened. These spectra are similar to those obtained with rat liver mitochondria. PMR spectra of promitochondria from each cell type dispersed in trifluoroacetic acid, or of extracted lipids or residual proteins similarly dispersed, were different only in detail. It appears, therefore, that in the native state membranes of unsaturated fatty acid-depleted promitochondria are structurally different from promitochondria of the other two cell types. The difference may be a consequence of altered lipid-to-protein ratios, and thus of changes in the extent of lipid domain formation in the membranes of these organelles.
Proton-magnetic-resonance studies of the lysine residues of ribonuclease A.
The amino groups of ribonuclease A (RNase-A) have been methylated with formaldehyde and borohydride to provide observable resonances for proton magnetic resonance (PMR) studies. Although enzymatic activity is lost, PMR difference spectroscopy and PMR studies of thermal denaturation show native conformation is largely preserved in methylated RNase-A. Resonances corresponding to the NH2-terminal alpha-amino and 10 xi-amino N-methyl groups are titrated at 220 MHz to obtain pK values. After correction for the effects of methylation, using values previously derived from model compound studies, a pK of 6.6 is found for the alpha-amino group, a pK of 8.6 for the xi-amino group of lysine-41 and pK values ranging from 10.6 to 11.2 for the other lysine xi-amino groups. Interactions between lysine-7 and lysine-41 or between the alpha-amino and xi-amino groups of lysine-1 have been proposed to account for deviations from simple titration behaviour. The correct continuities for the titration curves of the histidine H-2 proton resonances have been confirmed by selective deuteration of the H-2 protons. Titration curves for the H-2 proton resonances of histidine-12 and histidine-119 of methylated RNase-A show deviations from the titration curves for the native enzyme, indicating some alteration of the active-site conformation. In the presence of phosphate, titration curves for the H-2 proton resonances of histidine-12 and histidine-119 of methylated RNase-A indicate binding of phosphate at the active site, but these curves continue to show deviations from the titration behaviour of native RNase-A. The titration curve for the N-methyl resonance of lysine-41 is perturbed considerably by the presence of phosphate, which indicates a possible catalytic role for lysine-41.
Opportunistic gram-negative bacillary infections in leukemia. Oral manifestations during myelosuppression.
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Characterization of lac+ transductants of Streptococcus lactis.
A phage-mediated transducing system was used in studying certain physiological characteristics of S. lactis C2 wild type, lactose-negative mutants, and lactose-positive transductants. Lac(-) mutants, obtained by acriflavine treatment of the wild type, were similar to the wild type in all characteristics tested except they lacked beta-D-phosphogalactoside galactohydrolase (beta-Pgal) and could not transport [(14)C]lactose; they also had approximately 10% of the proteolytic ability than wild-type cells. The lactose-fermenting characteristic was transduced from the wild type to Lac(-) mutants. The Lac(+) transductants obtained were similar to the wild-type parent with respect to lactose fermentation and level of beta-Pgal activity (0.186 U of protein per mg). These transductants, however, had not regained full proteolytic ability and were similar to the Lac(-) mutant in this respect. Lactic acid production of the transductants in milk was approximately two-thirds that of the wild type. Data suggest that both the lactose-fermenting and proteolytic characters are carried on extrachromasomal particles (plasmids).
Calcification of selected strains of Streptococcus mutans and Streptococcus sanguis.
Nine strains of cariogenic Streptococcus mutans and two strains of Streptococcus sanguis were tested for their ability to form hydroxyapatite. The cells were examined by X-ray diffraction and electron microscopy for apatite crystals after growth in a synthetic calcification medium. Each of the test isolates, except for one strain of S. sanguis, produced intracellular mineral. Two strains of S. mutans formed both intra- and extracellular crystals. There was no apparent relationship between calcifiability and serotype.
Determination of the dissociation constants of the lysine residues of lysozyme by proton-magnetic-resonance spectroscopy.
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Effects of a simulated spacecraft environment on the oral microflora of nonhuman primates.
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Comparison of Gelman and Millipore membrane filters for enumerating fecal coliform bacteria.
Tests of two leading brands of membrane filters used for enumerating fecal coliform bacteria showed that Gelman GN-6 filters recovered statistically more colonies of bacteria than did Millipore HAWG 047SO filters from pure cultures incubated at either 35 C (the optimal growth temperature) or 44.5 C (the standard temperature for the fecal coliform test). Standard membrane filter procedures with M-FC broth base were used to enumerate the organisms. Densities of colonies incubated on Gelman filters at 44.5 C averaged 2.3 times greater than those on Millipore filters. Plate counts of the bacteria at both temperatures indicated that incubation at 44.5 C did not inhibit propagation of fecal coliform bacteria. For the pour plates, M-FC broth base plus 1.5% agar was used. This modified medium compared favorably to plate count agar for enumerating Escherichia coli. At 35 and 44.5 C, colony counts on Gelman filters agreed closely with plate counts prepared concurrently, but Millipore counts were consistently lower than plate counts, especially at 44.5 C. Comparative analyses of river water for fecal coliform bacteria by the membrane filter technique gave results comparable to those for the pure cultures.