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Biomedical subjects

E Brown

Publications and source records attributed to E Brown.

At least 253 records · Page 14Linked to original sources

The erythrocyte differential count in newborn infants.

The three-dimensional shape of erythrocytes is assessed by light microscopy using a simple technique to view glutaraldehyde-fixed erythrocytes. The technique and its standardization is described. Using this method the erythrocytes of adults have been compared to those of full-term and premature infants. In adults, the majority of erythrocytes are bowl-shaped at 37 degrees C and disc-shaped at room temperature. Newborn infants have significantly more bowl-shaped cells as well as significantly more irregularly shaped cells. Erythrocyte differential counts have been performed on a large series of patients to determine the normal range for each cell shape in adults, full-term, and premature infants. It is suggested that the study of erythrocyte morphology in haematologic disease in newborn infants requires three-dimensional assessment and quantitative data of normal values.

Adult↗

Studies on the mechanism of bacterial resistance to complement-mediated killing. III. C5b-9 deposits stably on rough and type 7 S. pneumoniae without causing bacterial killing.

Gram-positive cocci resist direct killing by serum. The mechanism of resistance was studied by measuring consumption of terminal complement components from serum and uptake of purified, radiolabeled C7 and C9 on rough and encapsulated type 7 Streptococcus pneumoniae. Extensive consumption of C5, C7, and C9 occurred when 5 X 10(8) rough or type 7 pneumococci were incubated for 1 hr in 10% pooled normal human serum (PNHS). Approximately 10,000 molecules of C7 and C9 bound per organism during the same period of incubation. Twenty to 30% of C7 and C9 was released from rough organisms. Release was not due to autolysis since it occurred with glutaraldehyde-fixed organisms as well as in S. pneumoniae that were rendered resistant to autolysis by growth in ethanolamine. Between 10 and 30% of bound 125IC9 counts were eluted from the rough and type 7 organisms by incubation in 1 M NaCl or 0.01 M EDTA, which suggests that bound C5b-9 was not attached by predominantly ionic interactions. Elution of 44 to 74% of 125IC9 from live and glutaraldehyde-fixed organisms by 1% sodium deoxycholate suggests that hydrophobic bonds are involved in C5b-9 attachment. Trypsin cleaved 67 and 55% of 125IC9 counts from live rough and type 7 S. pneumoniae, respectively which indicates that the bound complex is not protected by the cell wall from proteolytic attack. Serum resistance in S. pneumoniae does not represent a failure to form C5b-9 on the bacterial cell wall but apparently reflects a failure of the bound complex to penetrate the thick peptidoglycan layer.

Blood Bactericidal Activity↗

Multiple image integration: a new method in electron microscopy.

An optical 'flicker' method is described for the precise azimuthal and translational co-registration of many noisy but identical molecular images. Starting with a real micrograph of known biological objects showing no visible detail below 4 nm, a lattice of images of individual objects was synthesized by computer and translationally filtered, using real experimental data throughout. Detail was recovered conforming with known structural features of the object down to about 1.5 nm, and rotational analysis showed that the registration accuracy of the lattice elements was better than 0.5 nm on the object. Application to the straightening of real two-dimensional lattices with long-range distortion is discussed.

Animals↗

Linear mapping of tryptophan residues in Vesiculovirus M and N proteins by partial chemical cleavage.

Nonlimit chemical cleavage at tryptophan residues of protein labeled at the amino terminus afforded a simple procedure for generating specific fragments and for mapping tryptophan positions. A comparison of the matrix (M) and nucleocapsid (N) proteins of four members of the Vesiculovirus group by this procedure suggests considerable conservation of tryptophan number and location in the four serotypes examined.

Capsid↗

Characterization of the electrophoretic mobility mutation in the N protein of the tsD1 mutant of vesicular stomatitis virus New Jersey serotype.

Some isolates of the temperature sensitive mutant tsD1 of complementation group D of vesicular stomatitis virus of New Jersey serotype have a nucleocapsid (N) protein which shows an increased electrophoretic mobility on sodium dodecyl sulfate--polyacrylamide gel electrophoresis (SDS-PAGE) when compared with wild type. Utilizing techniques involving specific chemical cleavage at tryptophan or methionine residues, as well as enzymatic cleavage with carboxypeptidases A and B, we have determined that residues near the carboxyterminus are responsible for the electrophoretic difference of the mutant protein. We have further shown that there are no differences in the tryptic peptides of the mutant compared with the wild type or a non-ts revertant in this region of the protein. We have identified a tryptic peptide located outside the relevant carboxyterminal region which is distinct in mutant and revertant. We conclude that the mutation producing the aberrant electrophoretic mobility of N protein of the tsD1 mutant is a missense point mutation located at least 40 amino acid residues from the carboxyterminus and which interacts with a more proximal carboxyregion so as to influence electrophoretic mobility on SDS-PAGE.

Electrophoresis, Polyacrylamide Gel↗

Expression of Lyt-1 by a subset of B lymphocytes.

Using two-color flow cytometry and multiparameter data analysis, we have shown that the IgM bright, large subset of mouse splenic B lymphocytes express Lyt-1. This is not due to B cell uptake of immune complexes of Lyt-1 and antibody from T cells. The IgM bright cells of autoimmune NZB mice express more Lyt-1 than normal controls. This is because IgM containing plasmablasts, which are greatly increased in NZB spleens, are Lyt-1+. NZB spleen also contains more cells that are Lyt-1+ (but perhaps Lyt-1.2-), Thy-1.2 dull, and smaller in size than cells in normal mice. Thus, Lyt-1 is common to the T and B cell precursor or is induced independently during the ontogeny of T and at least one subset of B cells. We suggest that it be called Lyt-1.

Animals↗

Magnitude and duration of lung response to dexamethasone in fetal sheep.

Some cases of respiratory distress syndrome (RDS) occur after optimal prenatal exposure to glucocorticoids. To explore whether some of these cases might be due to a transient effect of glucocorticoids on developing fetal lung, we studied nine chronically catheterized sheep fetuses after infusion of 500 micrograms of dexamethasone phosphate. Daily efflux of disaturated phosphatidylcholine (DSPC) from fetal tracheal fluid was measured. Three cases showed no response, two showed an early sustained rise in DSPC, and four showed an unsustained response. We interpret these data as indicating that the fetus may respond in a variety of ways to glucocorticoids, depending possibly on such factors as stage of maturity, sex, dose, and duration of exposure.

Animals↗

Structure of intramembrane particles in proteoliposomes containing yeast mitochondrial ATPase.

Oligomycin-sensitive ATPase was isolated from yeast mitochondria and incorporated into phospholipid vesicles by cholate dialysis. The structure of the membranes was examined by freeze-fracture electron microscopy. Liposomes formed without the ATPase were small with diameters in the range 20 to 40 nm and they had smooth fracture faces. When the ATPase was introduced, larger vesicles formed (up to 500 nm in diameter) which bore intramembrane particles (IMPs) on their fracture faces. The IMP frequency was dependent on the ratio of protein to lipid used in the reconstitution. After unidirectional shadowing at an angle of 45 degrees, IMPs had a mean width of 12.7 nm and a mean shadow length of 5.9 nm. After rotary shadowing, the mean IMP diameter was 12.9 nm. When the amount of protein was higher than 1 mg/10 mg phospholipid in the initial incorporation mixture, the ATPase formed small hexagonal arrays in the liposome membranes. Computer-based image processing of such arrays showed that the IMPs had a centre-to-centre spacing of 13.7 nm. Calculations showed that each IMP may correspond to an oligomer of the ATPase.

Adenosine Triphosphatases↗

Transplancental cardioversion of intrauterine supraventricular tachycardia with digitalis.

Intrauterine congestive heart-failure caused by a supraventricular tachyarrhythmia was diagnosed in a fetus at 29-30 weeks' gestation. Major congenital malformations were excluded by sonography, amniocentesis, and fetal abdominal paracentesis, and those of the heart by intrauterine fetal echocardiography. The mother was given digoxin and the fetal tachycardia converted to sinus rhythm.

Adult↗

The isolation of three new high mobility group nuclear proteins.

In addition to the four high mobility group non-histone chromosomal proteins HMG 1, 2, 14 and 17 and histone H1, perchloric acid extracts of nuclei contain a number of other smaller low molecular weight proteins. Three of these proteins (HMG 18, 19A, and 19B) have been purified and characterized. Protein HMG 18 has high lysine and alanine contents, resembling histone H1. Proteins HMG 19A and 19B have high contents of basic and acidic amino acids and resemble HMG proteins 1, 2, 14 and 17. N-terminal sequence analyses of the proteins show that they are not degradation products of histones or the other HMG proteins. However, there are sequence similarities between HMG 18 and histone H5, and between HMG 19B and HMG 17, supporting the view that the HMG proteins and the lysine-rich histones are functionally related.

Amino Acid Sequence↗

Invasive pulmonary aspergillosis in an apparently nonimmunocompromised host.

Invasive aspergillosis generally occurs in patients with hematologic malignancies, neutropenia or other severe derangements of host defense. An adult patient without such a predisposition, and without a previous history of susceptibility to infections, had rapidly progressive respiratory failure associated with repeated growth of Aspergillus fumigatus on culture of sputum and bronchoscopy specimens. At autopsy he proved to have invasive pulmonary aspergillosis.

Aspergillosis↗

Structure--antitubulin activity relationship in steganacin congeners and analogues. Inhibition of tubulin polymerization in vitro by (+/-)-isodeoxypodophyllotoxin.

A new series of 23 synthetic analogues of the naturally occurring antitumor lignan steganacin was tested for the inhibition of microtubule assembly in vitro. Interestingly, (+/-)-isopicrostegane (I50 = 5 microM) was found to be almost as active as (+/-)-steganacin(I50 = 3.5 microM). On the other hand, racemic isodeoxypodophyllotoxin has an inhibiting activity of microtubule assembly comparable to that of (-)-podophyllotoxin, whereas (-)-isodeoxypodophyllotoxin is totally inactive.

Colchicine↗