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Biomedical subjects

L R Brown

Publications and source records attributed to L R Brown.

At least 19 recordsLinked to original sources

Use of fully deuterated micelles for conformational studies of membrane proteins by high resolution 1H nuclear magnetic resonance.

Micellar complexes of melittin with fully deuterated detergents have been studied by high resolution 1H nuclear magnetic resonance (NMR). The synthesis of deuterated micelles is described and it is shown that the 1H NMR spectrum of micelle-bound melittin is well resolved and suitable for detailed analysis by conventional high-resolution NMR methods. A preliminary characterization of micelle-bound melittin shows that interaction with the micelle results in different conformational and dynamic features for the hydrophobic and hydrophilic regions of the melittin amino acid sequence. The present experiments on melittin and preliminary results with other polypeptides and proteins demonstrate that in favourable cases high-resolution 1H NMR studies of the complexes formed between membrane proteins and deuterated micelles provides a viable method for conformational studies of membrane-bound proteins.

Bee Venoms

Physicochemical studies of the protein-lipid interactions in melittin-containing micelles.

Complexes of melittin with detergents and phospholipids have been characterized by fluorescence, circular dichroism, ultracentrifugation, quasi-elastic light scattering and 1H nuclear magnetic resonance (NMR) experiments. By ultracentrifugation and quasi-elastic light-scattering measurements it is shown that melittin forms stoichiometrically well-defined complexes with dodecylphosphocholine micelles consisting of one melittin molecule and approximately forty detergent molecules. Evidence from fluorescence, circular dichroism and 1H nuclear magnetic resonance experiments indicates that the conformation of melittin bound to micelles of various detergents or of diheptanoyl phosphatidylcholine is largely independent of the type of lipid and furthermore appears to be quite closely related to the conformation of melittin bound to phosphatidylcholine bilayers. 1H NMR is used to investigate the conformation of micelle-bound melittin in more detail and to compare certain aspects of the melittin conformation in the micelles with the spatial structures of monomeric and self-aggregated tetrameric melittin in aqueous solution. The experience gained with this system demonstrates that high resolution NMR of complexes of membrane proteins with micelles provides a viable method for conformational studies of membrane proteins.

Bee Venoms

Corneal edema with several hard corneal contact lenses.

Five patients were each fitted with polymethylacrylate (PMMA), BP Flex, and Polycon corneal contact lenses of the same dimensions. Corneal edema was monitored with a slit-lamp biomicroscope and pachometer. Lenses were worn in a double-masked and random sequence for periods of 6 hr. Patients developed less corneal edema with Polycon lenses than with PMMA lenses. There was no significant difference in corneal edema with PMMA and BP Flex lenses. Those patients who developed little corneal edema with optimum-fitting PMMA lenses also developed little edema with the BP Flex and Polycon lenses. Steeper-fitting PMMA and BP Flex lenses produced more corneal edema than optimum-fitting lenses made of the same materials, while steeper-fitting Polycon lenses produced only slightly more edema than the optimum-fitting Polycon lenses.

Adult

Comparison of the plaque microflora in immunodeficient and immunocompetent dental patients.

The nature and extent of the immune dysfunctions in 20 immunodeficient patients, as well as the immunocompetence of 22 control subjects, were verified by cell-mediated responsiveness and immunoglobulin quantitations. Comparisons of the microbial composition of supragingival plaque between the two populations showed that a greater number of immunodeficient than control subjects harbored Candida sp. and Staphylococcus sp. Conversely, a lower number of immunodeficient than control subjects harbored Streptococcus mutans. Also, patients with immune dysfunctions had a lower dental caries experience than their immunocompetent counterparts.

Antibody Formation

Systemic artery-to-pulmonary vein fistula in osteogenic sarcoma of the chest wall.

An arteriovenous fistula between the systemic and pulmonary circulations may be congenital, as in bronchopulmonary sequestration, or the communication may be acquired. Inflammatory disease, trauma, and, rarely, neoplasm have been implicated as possible causes of acquired communications. We describe a patient who had a systemic artery-to-pulmonary vein fistula that was secondary to a recurrent sarcoma of the chest wall. Review of the literature failed to reveal a previous report of a similar case.

Adult

Transconjugant analysis: limitations on the use of sequence-specific endonucleases for plasmid identification.

We used the sequence-specific endonucleases EcoRI, SmaI, BamHI, HsuI, and HaeIII as identification tools in following the conjugal transfer of the well-studied R plasmids Sa, R388, RP4, and R6K. Transfers were both intergeneric and intrageneric. Plasmid fingerprints were generated from both single- and combination-enzyme digests. The Sa transconjugants yielded plasmids showing consistent fingerprints for each of the respective endonucleases used, whereas the three other R-plasmid transconjugants showed fingerprint changes.

Base Sequence

Pulmonary processes of mature-appearing lymphocytes: pseudolymphoma, well-differentiated lymphocytic lymphoma, and lymphocytic interstitial pneumonitis.

Patients with pseudolymphoma, well-differentiated lymphocytic lymphoma, and lymphocytic interstitial pneumonitis were studied. Diagnoses were confirmed by recently developed immunochemical staining techniques. Radiographic findings in pseudolymphoma were different from those in well-differentiated lymphocytic lymphoma, and clinical findings in lymphocytic interstitial pneumonitis were different from those in the other two types of lesions. The interstitial infiltrate of lymphocytic interstitial pneumonitis had two patterns: basilar with an alveolar component and diffuse with associated honeycombing. Pseudolymphoma and lymphocytic interstitial pneumonitis are being polyclonal inflammatory processes without malignant potential. Well-differentiated lymphocytic lymphoma, a monoclonal neoplasm, often has an indolent course.

Humans

Comparison of whole lung tomography and computed tomography for detecting pulmonary nodules.

Detecting pulmonary metastasis is important when planning surgical therapy, radiotherapy, or chemotherapy in patients with known malignancy. A series of 91 patients was studied by both whole lung tomography and computed tomography (CT) of the lungs. More pulmonary nodules were detected with CT than with whole lung tomography in 32 (35%) of the patients. Of the 91 patients in the study, 31 had resection of some or all of the pulmonary nodules. In 27 patients, the nodules were primary or metastatic malignant lesions. Bilateral pulmonary nodules were detected with CT in 13 patients when whole lung tomography had demonstrated nodules in only one lung. CT has replaced whole lung tomography as the method preferred by the authors for detecting pulmonary nodules in selected patients at risk to develop pulmonary metastasis.

Adolescent

Nuclear-magnetic-resonance-spectroscopic studies of the amino groups of insulin.

The amino groups of insulin have been studied by 1H and 13C nuclear magnetic resonance spectroscopy in insulin, zinc-free insulin and methylated insulin. By difference spectroscopy it is possible to follow the shift with pH of the epsilon-CH2 and delta-CH2 proton resonances of lysine-B29 in insulin. In methylated insulin the dimethyl proton resonances of glycine-A1, phenylalanine-B1 and lysine-B29 can be followed as a function of pH. In native insulin pKapp values of 6.7 and 8.0 are obtained for phenylalanine-B1 and glycine-A1 (the assignment is tentative) and 11.2 for lysine-B29. Separate resonances have been observed from the lysine-B29 Nepsilon-(CH3)2 group for the monomeric and dimeric forms of methylated insulin, which indicates a small change in the environment of lysine-B29 on dimerisation. The nuclear magnetic resonance spectral characteristics of these groups are, in general, consistent with the overall structure of the crystal form of the 2-zinc insulin hexamer.

Amines

A spin label study of lipid oxidation catalyzed by heme proteins.

Rapid loss of the electron spin resonance signal from a variety of spin labels is observed when ferricytochrome c or metmyoglobin are combined with lipids. Evidence is presented that this loss of signal can be used as a sensitive method to study lipid oxidation catalyzed by heme proteins. Under aerobic conditions and with lipids which bind the heme protein, the kinetics of the oxidation process as observed by the spin label method are identical to the kinetics previously observed by measurements of oxygen uptake. Use of pre-oxidized lipids under anaerobic conditions indicates that cytochrome c reacts with a product of lipid oxidation. Kinetic studies of the anaerobic reaction indicate that cytochrome c reacts rapidly with lipid oxidation products in membrane areas far larger than the area occupied by cytochrome c, implying rapid transport of reactive species within the membrane interior in directions parallel to the membrane surface. Under anaerobic conditions, reaction of cytochrome c with lipid oxidation products appears to produce a relatively long lived (hours) species located in the hydrophobic portion of the membrane, which is capable of subsequent reaction with lipid-soluble spin labels.

Animals

Prevention of xerostomia-related dental caries in irradiated cancer patients.

Three caries preventative regimens: oral hygiene; oral hygiene and topical fluoride; and oral hygiene, typical fluoride, and sucrose restriction were evaluated in patients with cancer given xerostomia-producing radiotherapy. The oral hygiene-fluoride gel combination was remarkably effective in protecting these high risk patients from caries, regardless of the cariogenicity of the diet.

Adolescent

The effect of Skylab on the chemical composition of saliva.

The levels of specific proteins and electrolytes in stimulated whole saliva were monitored in Skylab crew members before and after each mission. With few exceptions, mission-associated compositional changes in saliva were relatively minimal. There were no changes in(formula see text), Cl-, albumin, or IgG concentrations. There were slight decreases in total protein coinciding with moderate saliva flow rate increases immediately before and after each flight. Other changes included diminutions in Na+ and lysozyme, and elevations in Mg++ and IgA. The IgA increase was the most pronounced mission-associated change observed.

Adult

Detection of pulmonary nodules by computed tomography.

In 11 of 23 patients, computed tomography of the chest detected pulmonary nodules that were not detected by conventional chest radiography or whole lung tomography. CT is recommended for patients suspected of having pulmonary metastasis and those with a solitary pulmonary nodule.

Carcinoma, Small Cell

A study of the lysyl residues in the basic pancreatic trypsin inhibitor using 1H nuclear magnetic resonance at 360 Mhz.

Fourier transform 1H nuclear magnetic resonance (NMR) experiments at 360 MHz using convolution difference techniques to improve the spectral resolution were employed to investigate the resonances of the lysyl residues in bovine pancreatic trypsin inhibitor. The observations in both native protein and in chemically modified protein containing Nepsilon-dimethyllsysine show that three of the four lysines extend predominantly freely into the solvent, whereas lysine-41 is involved in an intramolecular interaction with tyrosine-10. Since in the single crystal structure tyrosine-10 is involved in an intermolecular interaction with arginine-42 of the neighboring protein molecule, the NMR data thus reveal a local conformation difference for bovine pancreatic trypsin inhibitor in solution and in the crystalline form which appears to result primarily from intermolecular interaction in the crystal lattice.

Hydrogen-Ion Concentration