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Biomedical subjects

E S Olson

Publications and source records attributed to E S Olson.

At least 19 recordsLinked to original sources

Intracochlear pressure measurements related to cochlear tuning.

Pressure in turn one of the scala tympani (s.t.) was measured close to the basilar membrane (b.m.) and at additional positions as the pressure sensor approached and/or withdrew from the b.m. The s.t. pressure measured within about 100 microm of the b.m. varied rapidly in space at frequencies around the region's best frequency. Very close to the b.m. the s.t. pressure was tuned and scaled nonlinearly with sound level. The scala vestibuli (s.v.) pressure was measured at one position close to the stapes within seconds of the s.t. pressure and served primarily as a reference pressure. The driving pressure across the organ of Corti and the b.m. velocity were derived from the pressure data. Both were tuned and nonlinear. Therefore, their ratio, the specific acoustic impedance of the organ of Corti complex, was relatively untuned, and only subtly nonlinear. The impedance was inspected specifically for negative resistance (amplification) and resonance. Both were detected in some instances; taken as a whole, the current results constrain the possibilities for these qualities.

Acoustic Impedance Tests↗

Do antimicrobials have a role in preventing septicaemia following instrumentation of the urinary tract?

Urinary tract instrumentation is a significant cause of septicaemia. Review of the literature suggests that selective use of antimicrobials would reduce the risk of septicaemia as this varies between patients and with procedures. Antimicrobial prophylaxis is indicated for patients at high risk of endocarditis, or who are neutropenic. For patients without these risk factors, it is indicated for open, transurethral, or certain forms of laser prostatectomy or trans-rectal prostate biopsy. For cystoscopy, antimicrobials are indicated for patients with preoperative bacteriuria or a preoperative indwelling catheter. Single dose aminoglycosides or oral fluoroquinolones are the agents of choice with the exception of the prevention of endocarditis, where combinations active against streptococci are recommended. For other instrumentations, the risk of antimicrobial toxicity probably outweighs the benefits and a risk-reduction strategy is recommended. Further studies are required to provide definitive answers in many of these areas.

Adult↗

Direct measurement of intra-cochlear pressure waves.

The cochlear travelling wave is fundamental to the ability of the mammalian auditory system to resolve frequency. The seashell-shaped outer bone of the cochlea (the auditory inner ear) contains a spiral of cochlear fluid and the sensory tissue known as the cochlear partition. Sound travels down the ear canal to the eardrum, causing its flexible tympanic membrane to vibrate. This vibration is transmitted to the cochlea via the ossides. Motion of the stapes (the stirrup ossicle) sets the cochlear fluid in motion, which in turn sets the cochlear partition near the states in motion. The motion of the cochlear partition ripples down the cochlear spiral as a travelling wave, stimulating the cochlea's sensory hair cells. The wave peaks near the base (the stapes end) of the cochlea for high frequency tones and near the apex for low frequencies. The fundamental elements of the cochlear travelling wave are fluid pressure and motion and partition forces and motion. However, the wave's direct experimental study has to date relied almost solely on measurements of the partition motion. Here I report finely spaced measurements of intracochlear pressure close to the partition, which reveal the fluid component of the cochlear wave. The penetration depth of the wave is very limited, approximately 15 microm. Over a range of frequencies at least an octave wide, the depth is independent of frequency.

Animals↗

Characterization of Ca2+-dependent phospholipase A2 activity during zebrafish embryogenesis.

We have developed a simple fluorescent assay for detection of phospholipase A2 (PLA2) activity in zebrafish embryos that utilizes a fluorescent phosphatidylcholine substrate. By using this assay in conjunction with selective PLA2 inhibitors and Western blot analysis, we identified the principal activity in zebrafish embryogenesis as characteristic of the Ca2+-dependent cytosolic PLA2 (cPLA2) subtype. Embryonic cPLA2 activity remained constant from the 1-cell stage until the onset of somitogenesis, at which time it increased sharply. This increase was preceded by the expression of a previously identified zebrafish cPLA2 homologue (Nalefski, E., Sultzman, L., Martin, D., Kriz, R., Towler, P., Knopf, J., and Clark, J. (1994) J. Biol. Chem. 269, 18239-18249). By using a quenched BODIPY-labeled phosphatidylcholine that fluoresces only upon cleavage by PLA2, lipase activity was visualized in the cells of living embryos where it localized to perinuclear membranes.

Animals↗

Observing middle and inner ear mechanics with novel intracochlear pressure sensors.

Intracochlear pressure was measured in vivo in the base of the gerbil cochlea. The measurements were made over a wide range of frequencies simultaneously in scalae vestibuli and tympani. Pressure was measured just adjacent to the stapes in scala vestibuli and at a number of positions spaced by tens of micrometers, including a position within several micrometers of the basilar membrane, in scala tympani. Two findings emerged from the basic results. First, the spatial variation in scala tympani pressure indicated that the pressure is composed of two modes, which can be identified with fast and slow waves. Second, at frequencies between 2 and 46 kHz (the upper frequency limit of the measurements) the scala vestibuli pressure adjacent to the stapes had a gain of approximately 30 dB with respect to the pressure in the ear canal, and a phase which decreased linearly with frequency. Thus, over these frequencies the middle ear and its termination in the cochlea operate as a frequency independent transmission line. A subset of the data was analyzed further to derive the velocity of the basilar membrane, the pressure difference across the organ of Corti complex (defined to include the tectorial and basilar membranes) and the specific acoustic impedance of the organ of Corti complex. The impedance was found to be tuned in frequency.

Acoustic Impedance Tests↗

Not everything acid fast is Mycobacterium tuberculosis--a case report.

The Ziehl-Neelsen (ZN) stain is important in identifying organisms that are acid fast, principally Mycobacterium tuberculosis. However, decolorisation with a weaker acid concentration (for example 1% hydrochloric acid), often used in ZN staining in histology, can result in a wider variety of organisms appearing acid fast and can be a cause of misidentification. To illustrate this point, a patient is described with pulmonary nocardiosis who was misdiagnosed as having tuberculous empyema on pleural biopsy.

Aged↗

Osteopontin expression detected in adult cochleae and inner ear fluids.

Localization of protein epitopes and mRNA expression showed that there was a wide-spread distribution of osteopontin (OPN) within the membranous labyrinth of the adult mammalian cochleae. Immunoreaction product and mRNA were found within the stria vascularis, VIIIth cranial nerve, spiral ligament and limbus. Only specific cell types within these regions contained abundant OPN mRNA or protein, the main cell type being fibrocytes that populate the spiral limbus and spiral ligament. Epithelial cells that line the luminal surface of the stria vascularis (marginal cells) and neurons that compose the vestibular and auditory ganglia also showed high opn expression. The pattern of anti-OPN staining within membranous labyrinth was comparable to that observed in tissues such as gall bladder, breast and kidney. In those tissues, luminal epithelial cells, corresponding to the marginal cells of the stria vascularis, may be responsible for manufacturing and secreting OPN into the luminal fluids. consistent with those observations, we detected OPN epitopes in cochlear fluids withdrawn from the scalae media and tympani of the cochlea. We found that the protein species in cochlear fluid differed from those present in cerebrospinal fluid (CSF) suggesting that OPN exists in tissue-specific isoforms that may correspond to particular cellular functions.

Animals↗

Population genetics of Mycobacterium tuberculosis complex in Scotland analysed by pulsed-field gel electrophoresis.

The results of typing of 121 strains in the Mycobacterium tuberculosis complex by PFGE are presented. Every isolate from patients in Scotland over a 3-month period for M. tuberculosis and for 1 year for M. bovis were included along with several laboratory strains including those of BCG. The PFGE results suggest that the population structure of all the strains in this complex is distinctly simple with limited genetic diversity and also suggest that M. bovis is not a distinct species.

DNA Fingerprinting↗

Mapping the cochlear partition's stiffness to its cellular architecture.

The mechanical properties of the cochlear partition are fundamental to auditory transduction. We measured the point stiffness of the partition, in vivo, at up to 17 radial positions spanning its width, in the basal turn of the gerbil cochlea. We found the linear stiffness at the position that is most likely under the outer pillar cells to be 1.5 times greater than adjacent positions toward the ligament, in the pectinate zone, and five times greater than adjacent positions toward the lamina, in the arcuate zone. This radial variation seems to reflect the cellular geometry of the partition: The pillar cell is positioned as a structural element, and the basilar membrane supports a rich cellular structure in the pectinate zone, whereas it borders a fluid-filled space in the arcuate zone. The radial variation in partition stiffness we find will influence passive cochlear mechanics, and also bears on active cochlear mechanics, since it supports the plausibility of cells as effective force generators. Our results from measurements made in vivo extend the findings of previous measurements made in excised cochleae, in which the cellular contribution to stiffness was less evident.

Acoustic Stimulation↗

Electrically evoked otoacoustic emissions from the apical turns of the gerbil cochlea.

Electrically evoked otoacoustic emissions were measured with current delivered to the second and third turns of the gerbil cochlea. The emission magnitude and phase are dependent on the characteristic frequency (CF) of the stimulating microelectrode location. The death of the animal resulted in an initial increase in emission below the CF of the electrode location and a decrease in emission near the CF of the electrode location. The group delay of the electrically evoked emission phase data is twice as large as the acoustically evoked cochlear microphonic (CM) data obtained by Schmiedt and Zwislocki [J. Acoust. Soc. Am. 61, 133-149 (1977)]. This suggests the possibility of two separate propagation modes for the forward and reverse traveling waves.

Acoustic Stimulation↗

Necrobacillosis (Lemmiere's syndrome): a rare cause of necrotizing pneumonia.

The cases of four young and previously healthy patients with necrobacillosis are reported. All four patients presented with acute pharyngotonsillitis and pulmonary infiltrates due to metastatic abscesses, and had neutrophil leucocytosis and hypoalbuminaemia. Blood cultures grew Fusobacterium necrophorum and each patient responded to metronidazole.

Adolescent↗

Microbial desulfurization of dibenzothiophene: a sulfur-specific pathway.

Rhodococcus rhodochrous strain IGTS8 metabolizes dibenzothiophene, a model compound for organic sulfur in fossil fuels, in a sulfur-specific manner. Two routes of desulfurization have been identified. Under growth conditions, the intermediates are dibenzothiophene sulfoxide, dibenzothiophene sulfone, 2'-hydroxybiphenyl-2-sulfonate, and 2,2'-dihydroxybiphenyl. Stationary phase cells produce 2-hydroxybiphenyl as the desulfurized product and use the 2'-hydroxybiphenyl-2-sulfinate, rather than the sulfonate, as the key intermediate.

Oxidation-Reduction↗

Identification and Cloning of Genes Involved in Specific Desulfurization of Dibenzothiophene by Rhodococcus sp. Strain IGTS8.

The gram-positive bacterium Rhodococcus sp. strain IGTS8 is able to remove sulfur from certain aromatic compounds without breaking carbon-carbon bonds. In particular, sulfur is removed from dibenzothiophene (DBT) to give the final product, 2-hydroxybiphenyl. A genomic library of IGTS8 was constructed in the cosmid vector pLAFR5, but no desulfurization phenotype was imparted to Escherichia coli. Therefore, IGTS8 was mutagenized, and a new strain (UV1) was selected that had lost the ability to desulfurize DBT. The genomic library was transferred into UV1, and several colonies that had regained the desulfurization phenotype were isolated, though free plasmid could not be isolated. Instead, vector DNA had integrated into either the chromosome or a large resident plasmid. DNA on either side of the inserted vector sequences was cloned and used to probe the original genomic library in E. coli. This procedure identified individual cosmid clones that, when electroporated into strain UV1, restored desulfurization. When the origin of replication from a Rhodococcus plasmid was inserted, the efficiency with which these clones transformed UV1 increased 20- to 50-fold and they could be retrieved as free plasmids. Restriction mapping and subcloning indicated that the desulfurization genes reside on a 4.0-kb DNA fragment. Finally, the phenotype was transferred to Rhodococcus fascians D188-5, a species normally incapable of desulfurizing DBT. The mutant strain, UV1, and R. fascians produced 2-hydroxybiphenyl from DBT when they contained appropriate clones, indicating that the genes for the entire pathway have been isolated.

Journal Article↗

Metabolism of dibenzothiophene and naphthalene in Pseudomonas strains: complete DNA sequence of an upper naphthalene catabolic pathway.

From a soil isolate, Pseudomonas strain C18, we cloned and sequenced a 9.8-kb DNA fragment that encodes dibenzothiophene-degrading enzymes. Nine open reading frames were identified and designated doxABDEFGHIJ. Collectively, we refer to these genes as the DOX pathway. At the nucleotide level, doxABD are identical to the ndoABC genes that encode naphthalene dioxygenase of Pseudomonas putida. The DoxG protein is 97% identical to NahC (1,2-dihydroxynaphthalene dioxygenase) of P. putida. DoxE has 37% identity with cis-toluene dihydrodiol dehydrogenase. DoxF is similar to the aldehyde dehydrogenases of many organisms. The predicted DoxHIJ proteins have no obvious sequence similarities to known proteins. Gas chromatography with a flame ionization detector and mass spectroscopy confirmed that the DOX proteins convert naphthalene to salicylate and converting phenanthrene to 1-hydroxy-2-naphthoic acid. doxI mutants convert naphthalene to trans-o-hydroxybenzylidenepyruvate, indicating that the DoxI protein is similar to NahE (trans-o-hydroxybenzylidenepyruvate hydratase-aldolase). Comparison of the DOX sequence with restriction maps of cloned naphthalene catabolic pathway (NAH) genes revealed many conserved restriction sites. The DOX gene arrangement is identical to that proposed for NAH, except that the NAH equivalent of doxH has not been recognized. DoxH may be involved in the conversion of 2-hydroxy-4-(2'-oxo-3,5-cyclohexadienyl)-buta-2,4-dienoat e to cis-o-hydroxybenzylidenepyruvate. doxJ encodes an enzyme similar to NahD (isomerase). Our findings indicate that a single genetic pathway controls the metabolism of dibenzothiophene, naphthalene, and phenanthrene in strain C18 and that the DOX sequence encodes a complete upper naphthalene catabolic pathway similar to NAH.

Amino Acid Sequence↗

Aztreonam selective agar for gram positive bacteria.

Aztreonam blood agar, a new selective medium for Gram positive aerobic bacteria, was evaluated in comparison with conventional media for skin swabs. Aztreonam agar increased the number of isolates of Staphylococcus aureus by 17%. By producing purer growths on primary isolation, it significantly speeded up the identification and sensitivity testing of staphylococci and streptococci. All major Gram positive aerobic pathogens grow on this medium. Aztreonam agar is now an established addition to our culture media. It is used for swabs which are likely to have a mixed Gram positive and Gram negative flora, such as ears, burns, ulcers, and for the sputa of patients with cystic fibrosis.

Agar↗

In vivo measurement of basilar membrane stiffness.

Basilar membrane stiffness measurements were made in the base of the gerbil cochlea. Basilar membrane stiffness was determined by contacting the basilar membrane with a stainless steel needle (tip diameter 25 microns) attached to a force transducer, putting the needle/transducer structure through a low-frequency sinusoidal excursion with amplitude 5 or 25 nm, and measuring the restoring force exerted on the needle by the basilar membrane at the applied frequency. Stiffness was calculated as the amplitude of the restoring force divided by the amplitude of the excursion. Stiffness was measured over a 24-microns range of static displacements of the basilar membrane and is presented as stiffness versus static displacement. In cochleas that were not damaged during surgery the stiffness versus displacement characteristic usually had the following features: (1) an initial stiffness plateau with average stiffness 0.6 N/m; (2) a second plateau or level off with average stiffness 9.1 N/m; and (3) an increase in stiffness beyond the second plateau that was consistent with the theoretical stiffness-vs-displacement function of a beam. These features were present both pre- and post-mortem.

Animals↗

Frequency tuning in the electroreceptive periphery.

Our studies are concerned with the frequency tuning that is provided by the electrical resonance of tuberous electroreceptors. Frequency selectivity had previously been measured in the electroreceptor's afferent fibers, and resonant conductances in the electroreceptor cell membrane had been implicated in producing the selectivity. With transdermal application of sinusoidal current, we measured the frequency dependence of the impedance of small areas of the electroreceptor/skin structure of the weakly electric fish Sternopygus and Eigenmannia, and used our data to make a quantitative linear model of the structure. The qualitative form of the model was proposed by Bennett (1). The quantitative model allows us to estimate the frequency selectivity of the voltage across the innervated membrane of the electroreceptor cells. The frequency selectivity of electroreceptor cell voltage derived from our data are as sharp as the neural selectivity at frequencies close to the most sensitive frequency. Many of our measurements supported the linear system model. However, spontaneous electroreceptor voltage oscillations were detected in some of our specimens, suggesting that the electroreceptors can operate in a regime of active nonlinearity. A simple explanation for the observed oscillations is that they arise when damping in the electroreceptor cell's resonant membrane is negative for a limited span of membrane voltage surrounding the resting voltage. The response of oscillating units to sinusoidal current was compatible with this explanation. We report experimental observations bearing on the consequences of active nonlinearity for the frequency tuning of a resonant system.

Animals↗