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Biomedical subjects

H M Brown

Publications and source records attributed to H M Brown.

At least 91 records · Page 5Linked to original sources

Immunotherapy for grass pollenosis with allpyral allergen extracts. Improved results by objective control of treatment requirements.

Nasal provocation testing using a measured dose of dry grass pollen has been used as a method of controlling the amount of injection treatment required to achieve decreased sensitivity to grass pollen. This could seldom be shown at the usual top dose of 10,000 P.N.U., but by repeating the top dose until the reaction was negative, complete freedom from pollenosis was achieved in most cases. Strict criteria for assessment of results were used. Conventional dosage regimens produced only 27 percent excellent results, but 94 percent of those patients who became demonstrably nasal test-negative were completely or almost completely free from symptoms in the pollen season.

Adolescent↗

Isolation and characterization of indole-3-acetaldehyde reductases from Cucumis sativus.

In a continuing study of the biosynthetic pathway and regulatory mechanisms governing indole-3-acetic acid (auxin) formation, we report the isolation and initial characterization of three distinct indole-3-acetaldehyde reductases from cucumber seedlings. These enzymes catalyze the reduction of indole-3-acetaldehyde to indole-3-ethanol with the concomitant oxidation of NAD(P)H to NAD(P)+. Two of the reductases are specific for NADPH as second substrate, while the third is specific for NADH. The enzymes show a strong specificity for indoleacetaldehyde, with apparent Km values of 73mum, 130mum, and 400mum being calculated for the two NADPH-specific reductases and the NADH-specific reductase, respectively. Under no conditions of substrate concentration, incubation time, or assay method could the reverse reaction be observed. Chromatography on a calibrated Sephadex gel column led to estimated molecualr weights of 52,000 and 17,000 for the NADPH-specific reductases, while a value of 33,000 was obtained for the NADH-specific reductase. Both NADPH-specific reductases showed a pH optimum of 5.2 with a secondary optimum at 7.0, and both enzymes were activated by increasing ionic strength. The NADH-specific reductase showed a pH optimum of 7.0 with a secondary optimum at 6.1 and was slightly inhibited by increasing ionic strength.

Aldehyde Oxidoreductases↗

Intracellular Na+, K+, and C1- activities in Balanus photoreceptors.

Ion-sensitive microelectrodes were used to measure intracellular activities (aix) of Na+, K+, and C-1 in Balanus photoreceptors. Average values of aiNa, aiK, and aiCl were 28 mM, 120 mM, and 65 mM, respectively. Equilibrium potentials calculated from these average values were: Na+ +64 mV, K+ - 77 mV, and and Cl- -42 mV; ther average value of the resting potential for all cells examined was -41 mV. Long exposure to intense illumination produced measurable increases in aiNa. Classical Na+ - K+ reciprocal dilution experiments were analyzed with and without observed changes in aiK. As aoK was increased, the membrane depolarized, and aiK increased. Better agreement was found between the membrane potential and the directly determined EK than expected from the standard relation between Em and aoK. The latter produced pNa:pK estimates of the resting photoreceptor membrane that were higher than estimates based on data from the ion electrodes. Generally, Em was more negative than EK as aoK was increased. This is consistent with a significant chloride permeability in the dark-adapted photoreceptor.

Animals↗

Auxin biogenesis: subcellular compartmentation of indoleacetaldehyde reductases in cucumber seedlings.

Subcellular fractionation of cucumber (Cucumis sativus L.) seedlings was achieved, and two of the enzymes in the auxin biosynthetic pathway were localized. NADH-specific indoleacetaldehyde reductase activity was observed only in the cytosol fractions obtained from separated hypocotyl and cotyledon tissue. In contrast, a portion of the NADPH-specific indoleacetaldehyde reductase activity was associated with a microsomal fraction derived from these tissues. The NADPH-specific indoleacetaldehyde reductase was consistently found to be more firmly associated with the microsomal fraction derived from hypocotyls than with that from the cotyledons. These results indicate a division of the terminal steps of auxin biogenesis into at least two subcellular compartments.

Journal Article↗

Rapid extraction of grass pollen allergens and separation of their active fractions.

The immediate effects of nasal provocation tests with dry grass pollen, correlated with recent botanical evidence of almost instant release of allergens from the pollen wall, suggested that prolonged extraction of pollens was unnecessary and perhaps undesirable. It has now been shown that all the active allergens from undefatted dry grass pollens of the 12 major British species are extracted completely in 15 min. Gel chromatography of such rapid extracts has shown clear-cut separation of active from inactive material, as confirmed by skin and nasal provocation testing. It is probable that active fractions thus obtained contain the only pollen allergens of importance to clinical allergy. Further purification may produce specific allergens useful for the accurate standardisation of vaccines.

Allergens↗

Dual role for potassium in Balanus photoreceptor: antagonist of calcium and suppression of light-induced current.

1. The mechanism of reduction and final abolition of the depolarizing receptor potential of Balanus eburneus photoreceptors in K+-free saline was examined with electro-physiological techniques including voltage-clamp and ion specific electrodes. 2. An extended exposure to K+-free saline reduces the transient peak and the steady phases of the depolarizing receptor potential by approximately equal amounts. The process can be reversed in normal saline although the wave form of the response is often more rectangular upon recovery. Restoration of K+ induces a transient hyperpolarization of the resting membrane for several minutes. 3. The depolarizing receptor potential can also be restored in K+-free solution by reducing the Ca2+ concentration. This saline depolarizes the resting membrane, and the wave form of the depolarizing receptor potential assumes a rectangular configuration. 4. Voltage-clamp experiments revealed that an extended exposure to K+-free saline produced an extreme reduction of the inward light-induced current (LIC), but no detectable change in the membrane potential at which the current reverses sign. Membrane conductance in darkness showed little change. Reduction of the Ca2+ concentration from 20 to 0-2 mM in K+-free restored the current and produced a negative 8-10 mV shift in the zero current potential. There was also a significant decrease in membrane conductance in darkness. 5. Current-voltage relations of the membrane in K+-free, low Ca2+, or K+-free low Ca2+ salines were somewhat dependent upon the order the salines were presented. 6. Low Ca2+ saline (0-2 mM) by itself produced a -5 mV shift in the zero-current potential. Removing K+ in low Ca2+ produced an additional shift (-5 mV) in the zero-current potential.

Calcium↗

Spectral correlates of a quasi-stable depolarization in barnacle photoreceptor following red light.

1. Illumination of B. eburneus photoreceptors with intense red light produces a membrane depolarization that persists in darkness. This quasistable depolarization (latch-up) can be terminated with green light. The phenomenon was investigated with electrophysiological, spectrochemical, and microspectrophotometric techniques. 2. Latch-up was associated with a stable inward current in cells with the membrane potential voltage-clamped at the resting potential in darkness. The stable current could only be elicited at wave-lengths greater than 580 nm. 3. Light-induced current (LIC) was measured at various wave-lengths in dark-adapted photoreceptors with the membrane voltage-clamped to the resting potential. The minimum number of photons required to elicit a fixed amount of LIC occurred at 540 nm, indicating that the photoreceptor is maximally sensitive to this wave-length of light. The photoreceptor was also sensitive to wave-lengths in the near-U.V. region of the spectrum (380-420 nm). 4. Steady red adapting light reduced the magnitude of the LIC uniformly at all wave-lengths except in the near-U.V. region of the spectrum; sensitivity was reduced less in this region. 5. The spectrum for termination of the stable inward current following or during red light was shifted to the blue (peak about 510 nm) compared to the peak for LIC (peak about 540 nm). 6. Absorbance of single cells prepared under bright, red light decreased maximally at 480 nm following exposure to wave-lengths of light longer than 540 nm. 7. A pigment extract of 1000 barnacle ocelli prepared under dim, red light had a maximum absorbance change at 480 nm when bleached with blue-gree light. 8. There was no evidence in the latter two experiments of photointerconversion of pigments with absorbance maxima at 480 and 540 nm. Rather, the maximum absorption of the bleaching products seemed to occur at wave-lengths shorter than 420 nm. 9. Since latch-up induction occurs at wave-lengths longer than 580 nm, it may depend on the 540 pigment or on an undetected red absorbing pigment. 10. A photolabile pigment at 480 nm correlated most closely with termination of the stable inward current associated with latch-up.

Adaptation, Ocular↗

Ionic mechanism of a quasi-stable depolarization in barnacle photoreceptor following red light.

1. The membrane mechanism of a quasi-stable membrane depolarization (latch-up) that persists in darkness following red light was examined in barnacle photoreceptor with micro-electrode techniques including voltage-clamp and Na+-sensitive micro-electrodes. 2. Current-voltage (I-V) relations of the membrane in darkness following red light (latch-up) and in darkness following termination of latch-up with green light, indicate that latch-up is associated with an increase of membrane conductance. 3. The latch-current (membrane current in darkness following red light minus membrane current in darkness following a gree flash that terminates latch-up) was inward at the resting potential, reversed sign at about +26mV (mean of six cells), and became outward at more positive membrance potentials. 4. Current-voltage relations of the membrane during green light (no latch-up) closely resembled those during latch-up. The light-induced current (LIC) elicited by green ligh (membrane current during the light flash minus membrane current in darkness following the light flash) was inward from the resting potential to +26mV (mean of six cells), then reversed sign and became outward. 5. The latch-current and LIC were both augmented in reduced Ca2+ solutions and decreased as Na-+ was reduced at a fixed Ca2+ concentration. 6. Both LIC and latch-current reversed sign at a more negative membrane potential (increment V equals 14mV) in solutions containing one quarter the normal amount of Na+. 7. The internal Na-+ activity (a-iNa) of a photoreceptor increased from about 10-18 mM upon illumination with long steps of intense red or white illumination. Five minutes in darkness after white light, a-iNa had recovered significantly, whereas a-iNa remained elecated following red illumination. 8. Latch-up seems to be a persistence in darkness of the same membrane mechanism that normally occurs during illumination; i.e. a conductance increase to Na+ ions. Ca2+ ions act primarily to suppress this current. There is evidence for a net Na+ influx during illumination that is sustained in darkness during latch-up.

Animals↗

Beclomethasone dipropionate steriod aerosol in treatment of perennial allergic asthma in children.

Thirty-one chronic perennial asthmatics aged from 2(1/2) to 16 years were treated with beclomethasone dipropionate pressurized aerosols for up to 20 months. Of these, 16 patients dependent on oral corticosteroid or corticotrophin for up to 11 years were successfully transferred to this treatment, with one exception. Steroid withdrawal symptoms were slight. Loss of weight, disappearance of Cushingoid features, and resumption of growth indicated lack of systemic side effects. Fifteen others inadequately controlled on bronchodilators or disodium cromoglycate, were also effectively treated, and no clinical evidence of adrenal suppression was noted.

Administration, Oral↗

Light response of a giant Aplysia neuron.

Illumination of an Aplysia giant neuron evokes a membrane hyperpolarization which is associated with a membrane conductance increase of 15%. The light response is best elicited at 490 nM: the neuron also has an absorption peak at this wavelength. At the resting potential (-50 to -60 mV) illumination evokes an outward current in a voltage-clamped cell. This current reverses sign very close to E(K) calculated from direct measurements of internal and external K(+) activity. Increases in external K(+) concentration shift the reversal potential of the light-evoked response by the same amount as the change in E(K). Decreases in external Na(+) or Cl(-) do not affect the response. Therefore, the response is attributed to an increase in K(+) conductance. Pressure injection of Ca(2+) into this neuron also hyperpolarizes the cell membrane. This effect is also due largely to an increase in K(+) conductance. The light response after Ca(2+) injection does not appear to be altered. Pressure injection of EGTA abolished or greatly reduced the light response. The effect was reversible. We suggest that light acts upon a single pigment in this neuron, releasing Ca(2+) which in turn increases K(+) conductance, thereby hyperpolarizing the neuronal membrane.

Animals↗

Ionic basis of the photoresponse of Aplysia giant neuron: K + permeability increase.

The giant neuron of the Aplysia abdominal ganglion hyperpolarizes during illumination. The light-initiated potential change is associated with an increase of membrane conductance. It reverses sign at the potassium equilibrium potential (about -83 millivolts), which was determined from direct measurements of internal potassium activity. The membrane hyperpolarization is produced entirely by a light-induced increase in potassium permeability.

Animals↗

Beclomethasone dipropionate: a new steroid aerosol for the treatment of allergic asthma.

Beclomethasone dipropionate was used in pressurized aerosols for the treatment of 60 cases of chronic allergic asthma for up to 15 months. Twenty-eight out of 37 cases were transferred to this treatment after being dependent on oral steroids for up to 16 years. Nineteen out of 23 other asthmatics not dependent on steroids were also completely controlled. No biochemical evidence of adrenal suppression was found. Steroid withdrawal symptoms were often a problem, suggesting absence of systemic absorption. The precise mode of action and metabolic fate of this corticosteroid are not yet known.

Adolescent↗