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Biomedical subjects

J N Brown

Publications and source records attributed to J N Brown.

At least 19 recordsLinked to original sources

Apical hair cells and hearing.

This study assessed the contribution of the apical hair cells to hearing. Guinea pigs, chinchillas and monkeys were behaviorally trained using positive reinforcement to respond to pure-tone stimuli. When a stable audiogram had been determined, each subject received one of three experimental treatments: ototoxic drug administration, low-frequency noise exposure, or the application of a cryoprobe to the bony wall of the cochlear apex. After post-treatment audiograms stabilized, subjects were euthanized and the percentage of hair cells remaining was assessed by light microscopy. Results indicate that a redundancy of encoding mechanisms exist in the mammalian cochlea for low-frequency stimuli. They also suggest that a very small percentage of apical hair cells are sufficient for some low-frequency hearing. Finally, data from this and other studies suggest that the low-frequency threshold shift caused by the loss of a certain percentage of apical hair cells is less pronounced than the high-frequency threshold shift caused by the loss of a comparable percentage of basal hair cells. These data agree with anatomical and electrophysiological evidence that functional as well as anatomical differences may exist between the apex and base of the cochlea.

Animals

Blood pressure and other physiological responses in awake and anesthetized guinea pigs.

The effect of combinations of injectable anesthetics on mean arterial blood pressure, blood gases, heart rate and respiration of the guinea pig (NIH Outbred strain) was investigated. After a 30 minute period in which baseline resting cardiorespiratory measurements were obtained, five groups of six pigmented animals having indwelling carotid cannulas were anesthetized with (a) ketamine hydrochloride (30 mg/kg, im)/xylazine (5 mg/kg, im); (b) sodium pentobarbital (15 mg/kg, ip)/fentanyl-droperidol (0.4 mg/kg, im); (c) diazepam (5mg/kg, ip)/fentanyl citrate (0.32 mg/kg, im); (d) diazepam (5 mg/kg, ip)/alphaxalone-alphadolone acetate (45 mg/kg, im); or (e) 1% alpha-chloralose-40% urethane (0.8 ml/100g, ip). Animals were not respirated artificially and no supplemental doses of anesthetic were given. Resting blood pressure in awake animals was measured over time for as long as cannulas remained patent (109 measurements). Mean resting blood pressure, for this strain of guinea pigs, was determined to be 53.1 +/- 4.2 mmHg. There was no indication that mean arterial blood pressure changed with age in animals varying in weight from 215 g to 550 g. Under diazepam/fentanyl, blood pressure rose significantly above resting level to a mean of 71.1 +/- 6.1 mmHg. With the other four combinations, blood pressure stabilized near, but below pre-anesthesia levels (ketamine/xylazine 47.1 +/- 6.8 mmHg; pentobarbital/fentanyl-droperidol, 46.9 +/- 3.2 mmHg; diazepam/alphaxalone-alphadolone, 47.8 +/- 4.8 mmHg; chloralose-urethane, 51.0 +/- 1.2 mmHg). Under diazepam/alphaxalone-alphadolone and chloralose-urethane, respiration was depressed and blood gas levels deviated from normal to the extent that artificial ventilation would be necessary to maintain an adequate physiological state.

Anesthesia

Potential radiosensitizing agents. Dinitroimidazoles.

New compounds of the nitroimidazole series have been synthesized as radiosensitizers which selectively sensitize hypoxic cells to the lethal effect of radiation. The reaction of 2,4(5)-dinitroimidazole (2) with chloroethanol or hydrochloric acid yielded 4(5)-nitro-5(4)-chloroimidazole (3), which upon reaction with ethylene oxide yielded the 4-nitro-5-chloroimidazole-1-ethanol (6). Reaction of 2 with ethylene oxide resulted in a mixture of two compounds, the 2,4-dinitroimidazole-1-ethanol (4) and 2,3-dihydro-5-nitroimidazo[2,1-b]oxazole (5). The structure of the new heterocyclic compound 5 was confirmed by 1H NMR, mass spectrum, and X-ray crystallography. These agents were tested for their ability to sensitize hypoxic Escherichia coli cells to killing by ionizing radiation. Compound 4 was found to be the most active agent of this series of compounds.

Chemical Phenomena

Peptide--water association in peptide crystals.

The structures of 37 peptide crystals, containing 78 water-peptide hydrogen bonds and 77 other hydrogen bonds involving water, were surveyed to identify the geometry of peptide backbone hydration. In the sample, hydration of peptide carbonyl occurred more frequently than hydration of peptide N--H. The most probable value of the C'=O ... O water angle was near 138 degrees, considerably greater than the 120 degrees to the axis of a lone electron pair on the carbonyl oxygen. Associated water oxygens tended to be in the plane of the peptide bond, bui--H and Ci+1=O atoms, was common in glycine-containing cyclic hexapeptides. The distribution of angles between two hydrogen bonds at a single water molecule, as defined by the three nonhydrogen atoms involved, was centered near the tetrahedral angle.

Amino Acid Sequence

Tricarboxylic acid cycle enzyme activities in adult Schistosoma mansoni and Schistosoma japonicum.

Reduced tricarboxylic acid cycle enzyme activities were found in paired adult Schistosoma mansoni and S. japonicum in comparison to those reported for S. mansoni cercariae (Coles, 1973). Succinate dehydrogenase activity, which has not been previously reported for either adult blood fluke, is more than twice as great in paired adult S. japonicum as in paired adult S. mansoni, but the activity is low in both species of adult worms. The similar low levels of tricarboxylic acid cycle enzyme activities which occur in adult S. mansoni and S. japonicum further substantiate the fact that anaerobic glycolysis is the major energy source in adults of both species.

Animals

Schistosoma mansoni and Schistosoma japonicum: comparison of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities in adults.

Glucose-6-phosphate dehydrogenase activity in paired adult Schistosoma mansoni is about twice as great as in paired adult Schistosoma japonicum. 2. 6-phosphogluconate dehydrogenase activity accounts for 25.8% of the measured production of reduced nicotinamide adenine dinucleotide phosphate (NADPH) in S. japonicum but only 8.6% of the measured production of NADPH in S. mansoni. 3. These data suggest a species difference in 6-phosphogluconate metabolism.

Animals

A simple low-cost critical point dryer with continuous flow dehydration attachment.

A simple low-cost critical point dryer with continuous flow dehydration attachment is described. By using the critical point pressure chamber for all fluid exchanges, loss of material and air-drying artefacts due to specimen handling are reduced. An operating schedule that allows the optimum path around the critical point process to be followed is proposed.

Cells, Cultured

Inhibition of key glycolytic enzymes from rabbit kidney medulla by free fatty acids in vitro.

In vitro incubation of key glycolytic enzymes in supernatant fluids from rabbit kidney medulla with increasing concentrations of sodium laurate resulted in progressive inhibition of hexokinase, phosphofructokinase and pyruvate kinase. A corresponding reduction in the production of lactate from glucose was also observed. The possible effects of these enzyme inhibitions on the naturesis observed during fasting are discussed.

Animals

The avian erythrocyte: a study of fixation for electron microscopy.

The quality of ultrastructural preservation of the avian erythrocyte achieved using various fixation techniques is evaluated. Different combinations of initial fixatives, buffers and post-fixation procedures were tested as well as variations in fixative osmolarity, pH and temperature. Of the commonly used initial fixatives (glutaraldehyde, acrolein and formaldehyde), 2% glutaraldehyde, alone in a slightly hypertonic buffer containing divalent ions, produced optimum erythrocyte preservation. The osmolarity was balanced using a non-electrolyte such as a sucrose. The addition of 12% hexylene glycol to the buffer solutions also improves erythrocyte preservation, as evidenced by the increased stability of the marginal microtubules, microfilaments and proteinaceous material. The use of Spurr low-viscosity epoxy resin enables the cells to be collected using low gravitational centrifugation.

Acrolein