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Biomedical subjects

A M Brown

Publications and source records attributed to A M Brown.

At least 19 recordsLinked to original sources
PubMed1992

Mechanical filtering of sound in the inner ear.

We have studied the distortion generated by the cochlea to gain insight into the mechanisms responsible for the sharp tuning or 'frequency selectivity' of the inner ear. We used two stimulating tones of moderate intensity which are progressively separated in frequency, and measured the ear canal cubic distortion components which are generated as a consequence of the stimulus interaction in the cochlea. We inferred that the distortion is generated from the frequency region of the higher of the two stimulus tones and that it is then band-pass filtered by a structure which is tuned to a frequency just over half an octave below that of the high-frequency tone. We suggest that the structure responsible for this band-pass filtering is the tectorial membrane, and we conclude that our results support theories of cochlear mechanics in which resonances due to the tectorial membrane interact with those of the basilar membrane to enhance the frequency selectivity of the inner ear.

Acoustic Stimulation↗
PubMed1992

Cloning and characterization of a novel Drosophila Wnt gene, Dwnt-5, a putative downstream target of the homeobox gene distal-less.

The Wnt gene family in vertebrates comprises at least 11 distinct genes but the only family member previously identified in Drosophila has been the segment polarity gene wingless (wg), the ortholog of vertebrate Wnt-1. In this report we describe the isolation of a novel Drosophila Wnt gene, Dwnt-5, which differs significantly from wg in both the pattern of its expression during embryogenesis and the predicted structure of its product. Dwnt-5 encodes a polypeptide of 112 kDa, which is more than twice as large as the products of previously known Wnt genes. The protein shares homology with other Wnt sequences in its carboxy-terminal half only and is most closely related to the products of vertebrate Wnt-5a and Wnt-5b. Dwnt-5 is expressed in a complex pattern during Drosophila embryogenesis. At the extended germ band stage, however, transcripts accumulate specifically in the nascent limb primordia of the head and thoracic segments. We show that this elevated expression depends on the activity of the homeobox gene Distal-less (Dll) and suggest that the Dwnt-5 gene may constitute a downstream target of Dll that acts in the specification of these primordia.

Amino Acid Sequence↗
PubMed1992

A spleen necrosis virus-based retroviral vector which expresses two genes from a dicistronic mRNA.

We have investigated a novel strategy for coexpressing two genes from a retroviral vector. The 5' nontranslated leader region of at least some picornavirus RNAs contains a sequence that can act as an internal ribosome entry site allowing initiation of translation at a downstream AUG codon in a 5' cap-independent manner. To investigate whether such a sequence can function in the context of a retroviral vector, we constructed a spleen necrosis virus-based vector carrying two selectable marker genes separated by the leader region of encephalomyocarditis virus. This vector was genetically stable and efficiently expressed both markers from a single dicistronic transcript. Since the expression of two genes by other strategies in retroviral vectors can often be problematic, these results offer a promising new approach for the design of "double gene" retroviral vectors.

Animals↗
PubMed1992

Inhibition of slow TTX-insensitive inward current by the anticonvulsant carbamazepine in an identified neuron of Lymnaea stagnalis.

1. Pentylenetetrazol (PTZ), induces tonic depolarization and bursting activity in an identified neuron, B1, of Lymnaea stagnalis. This is due in part to activation of a slow, tetrodotoxin-insensitive inward sodium current. 2. Carbamazepine (CBZ) reversed the effect of PTZ on both membrane potential and inward current, after a delay of up to 5 min. CBZ alone had no effect on voltage or current responses. 3. These results suggest that CBZ blocks the slow sodium current, possibly via a decrease in intracellularly stored calcium ions.

Action Potentials↗
PubMed1992

Properties of cyclic AMP-dependent inward current in two identified neurons of the snail Lymnaea stagnalis.

1. Intracellular iontophoresis of cyclic AMP induces a slow, inward sodium current in identified neurons B1 and RPD1 of Lymnaea stagnalis, which is TTX-insensitive and voltage independent. 2. High extracellular Ca2+ or Co2+ ions cause a reduction in the amplitude of the current, whereas low Ca2+ enhances it. 3. Agents known to increase intracellular cyclic AMP lead to depolarization and increased activity in B1, but RPD1 is unaffected. 4. The properties of cyclic AMP-stimulated inward current in neurons of L. stagnalis are compared with those of similar currents in other gastropod species.

Action Potentials↗
PubMed1979

Coronary pressor reflexes.

The heart differs from other cardiovascular reflexogenic structures because it has two prominent inputs to the central nervous system. On input is spinal and is mediated by afferent cardiac sympathetic nerve fibers. The other is medullary and is mediated by afferent vagal fibers. The number of fibers projecting centrally appears to be similar in the two systems. The reflex effects produced by excitation of the two inputs are complicated and can be either pressor or depressor. However, reflex pressor effects seem to be more prominant for the spinal input and reflex depressor effects more prominent for the medullary input.

Animals↗
PubMed1979

Evidence for a magnesium- and ATP-dependent calcium extrusion pump in dog erythrocytes.

Intact dog erythrocytes, whose Ca2+ permeability had been increased with A23187 still maintained intracellular Ca2+ below electrochemical equilibrium indicating that they could extrude Ca2+. This extrusion required no Na+ gradient but apparently depended on intracellular ATP and Mg2+ suggesting that it was mediated by an ATP-fuelled Ca2+ pump.

Adenosine Triphosphate↗
PubMed1979

Ultrastructure of Aplysia neurons having different degrees of light sensitivity.

The relationship between ultrastructure and photosensitivity of pigmented neurons of the abdominal ganglion of Aplysia californica was investigated using electron microscopy and electrophysiological methods. Four identified neurons of similar light microscopic appearance were examined; two are photoresponsive and two are not. Illumination hyperpolarizes both responsive neurons. One of them, R2, requires roughly 100 times greater light intensities than does the other, the ventral photoresponsive neuron (VPN), for similar responses. Two neurons lying adjacent to VPN and similar in appearance to VPN do not have measurable electrophysiological responses to even the highest light intensities. All four neurons contained lipochondria, pigmented organelles associated with the light response. Therefore the presence of these organelles is not the only requirement for light sensitivity in these neurons. Illumination appeared to increase the number of membranous lipochondria in both R2 and the ventral neurons, but only in R2 was this increase significant. Factors such as the concentration of lipochondria near the plasma membrane may affect quantitative aspects of the light response, but in the insensitive cells the lipochondria are apparently uncoupled from other factors required for the light response.

Animals↗
PubMed1979

Photoresponses of a sensitive extraretinal photoreceptor in Aplysia.

1. The light-evoked membrane current, photo-current, of an extraretinal photo-receptor, the ventral photoresponsive neurone (v.p.n.), in the abdominal ganglion of Aplysia californica, was studied using the voltage clamp method. Flashes and steps of monochromatic light were used as stimuli. 2. Flashes of light 100 msec in duration elicit slowly developing outward currents which peak at 5--10 sec and then return to dark levels within 30--60 sec. 3. The peak of the action spectrum of v.p.n. is at 470 nm and is similar to the peak for R2, another photoresponsive extraretinal Aplysia neurone, and to the peak of absorption spectra of molluscan rhodopsins. V.p.n. also contains membrane-bound cytoplasmic pigmented granules similar to those found in R2, and these are thought to mediate the light response. 4. Photo-current is associated with an increase in membrane conductance. In normal sea water photo-current has a reversal potential at the K equilibrium potential, EK and the reversal potential has a Nernstian relationship with external K concentration. The current--voltage relationships for peak and steady-state photo-current are fitted by the same constant field equation; currents measured when voltage was changed in steps at peak photo-current also have a similar relationship with voltage. The results are similar when saturating or non-saturating light intensities were used. Thus it appears that the light-activated K+ conductance is neither time nor voltage dependent. 5. Minimally detectable responses occurred at flash photon densities of 10(12) photons cm-2 which is 10(-3) that for R2. This value is comparable to those reported for retinal photoreceptors of Pecten irradians, a scallop, and Salpa democratica, a pelagic tunicate, and is lower than values reported for extraretinal photoreceptors such as the pineal photoreceptors of Salmo gairdnerii irideus, the rainbow trout, and the caudal photoreceptor in the sixth abdominal ganglion of Procambarus clarkii, a crayfish. 6. V.p.n. has a linear amplitude response range for low intensities of light and a non-linear range that saturates at high intensities. In the accompanying paper the response wave form and its temperature dependence are interpreted according to a diffusion-based model.

Animals↗
PubMed1979

The role of diffusion in the photoresponse of an extraretinal photoreceptor of Aplysia.

1. Membrane currents produced by flashes and steps of light (photo-current) were recorded from the ventral photoresponsive neurone of Aplysia californica. The effects of background illumination and changes in temperature were also examined. 2. The falling phase of the response wave form may be separated into two components with time constants of 10--12 sec and 50 sec. 3. Background illumination reduced the response amplitude to light impulses without appreciably altering the response wave form. 4. Lowering the temperature greatly reduced the amplitude of the photo-current with a Q10 of 2.91 (25--15 degrees C) and greatly prolonged the duration of the response. 5. Because of the relatively large distance between the plasma membrane and the pigmented cytoplasmic lipochondria where light is absorbed, a diffusion-based model with Ca as the internal-transmitter (Andresen & Brown, 1979) was developed. 6. In this model diffusion of Ca2+ released from the lipochondria upon photon absorption is slowed by the reversible uptake of Ca2+ at cytoplasmic binding sites. Ca2+ interacts with sites at the plasma membrane to increase GK and Ca2+ levels are subsequently restored by irreversible uptake processes. Ca2+ release and its adsorption and desorption from the more numerous plasma membrane binding sites were assumed to be instantaneous with respect to the duration of the light-evoked response. 7. The linearized model equations adequately predict the experimental response wave forms, the effects of temperature, and saturation of the steady-state amplitude--stimulus relationship. Aside from amplitude scaling, no curve-fitting was used. 8. The model also gives realistic values for the cytoplasmic diffusion coefficient of Ca and the net rate of Ca efflux required to restore dark Ca activity.

Animals↗
PubMed1978

A calcium-activated potassium channel present in foetal red cells of the sheep but absent from reticulocytes and mature red cells.

Red cells of adult sheep, like those of other ruminants, lack the calcium-activated potassium channel which is present in the membrane of human red cells. Since the activities of other transport systems in the sheep red cell are known to decrease during maturation of the cell or during development of the animal it was investigated whether the K+ channel is present in red cells from younger animals or in reticulocytes. Using the divalent cation ionophore A23187 to increase the intracellular Ca of intact cells, it was found that the K+-selective channel is present in foetal red cells from the foetus or newborn animal but not in reticulocytes. The presence of the channel showed no dependence on the K+ genotype of the sheep and was not associated with either "high K+"- or "low K+"-type Na+ pump. No Ca2+-dependent change in K+ permeability was found in red cells from either newborn or adult donkeys suggesting that its presence in the red cells of the foetus may not be general. The role of the K+ channel in the mammalian red cell and the relationship between the K+ channel and the Na+ pump are discussed.

Animals↗
PubMed1978

Properties of internally perfused, voltage-clamped, isolated nerve cell bodies.

The membrane properties of isolated neurons from Helix aspersa were examined by using a new suction pipette method. The method combines internal perfusion with voltage clamp of nerve cell bodies separated from their axons. Pretreatment with enzymes such as trypsin that alter membrane function is not required. A platinized platinum wire which ruptures the soma membrane allows low resistance access directly to the cell's interior improving the time resolution under voltage clamp by two orders of magnitude. The shunt resistance of the suction pipette was 10-50 times the neuronal membrane resistance, and the series resistance of the system, which was largely due to the tip diameter, was about 10(5) omega. However, the peak clamp currents were only about 20 nA for a 60-mV voltage step so that measurements of membrane voltage were accurate to within at least 3%. Spatial control of voltage was achieved only after somal separation, and nerve cell bodies isolated in this way do not generate all-or-none action potentials. Measurements of membrane potential, membrane resistance, and membrane time constant are equivalent to those obtained using intracellular micropipettes, the customary method. With the axon attached, comparable all-or-none action potentials were also measured by either method. Complete exchange of Cs+ for K+ was accomplished by internal perfusion and allowed K+ currents to be blocked. Na+ currents could then be blocked by TTX or suppressed by Tris-substituted snail Ringer solution. Ca2+ currents could be blocked using Ni2+ and other divalent cations as well as organic Ca2+ blockers. The most favorable intracellular anion was aspartate-, and the sequence of favorability was inverted from that found in squid axon.

Animals↗
PubMed1978

The calcium current of Helix neuron.

Calcium current, Ica, was studied in isolated nerve cell bodies of Helix aspersa after suppression of Na+ and K+ currents. The suction pipette method described in the preceding paper was used. Ica rises to a peak value and then subsides exponentially and has a null potential of 150 mV or more and a relationship with [Ca2+]o that is hyperbolic over a small range of [Ca2+]o's. When [Ca2+]i is increased, Ica is reduced disproportionately, but the effect is not hyperbolic. Ica is blocked by extracellular Ni2+, La3+, Cd2+, and Co2+ and is greater when Ba2+ and Sr2+ carry the current. Saturation and blockage are described by a Langmuir adsorption relationship similar to that found in Balanus. Thus, the calcium conductance probably contains a site which binds the ions referred to. The site also appears to be voltage-dependent. Activation and inactivation of Ica are described by first order kinetics, and there is evidence that the processes are coupled. For example, inactivation is delayed slightly in its onset and tau inactivation depends upon the method of study. However, the currents are described equally well by either a noncoupled Hodgkin-Huxley mh scheme or a coupled reaction. Facilitation of Ica by prepulses was not observed. For times up to 50 ms, currents even at small depolarizations were accounted for by suitable adjustment of the activation and inactivation rate constants.

Animals↗
PubMed1978

Selective stimulation and differentiation of early antigens in lymphoblastoid cell lines producing Epstein-Barr-like viruses.

Comparisons of early antigens (EA) of EBV-related lymphotropic herpes virus of Old World primates have proved difficult to accomplish because antigen levels are low in infected cells and the ratio of virus capsid antigen to EA is generally high. To overcome these difficulties, we have developed a procedure which combines antigen stimulation with inhibition of late virus functions and results in the selective stimulation of EA. Using this procedure, we have examined the EA of EBV, herpesvirus papio, h. pongo, and h. pan. The results show that the EA of these viruses are composed of both R (restricted) and D (diffuse) components and that the EA, while related, are distinguishable.

Animals↗