Regulation of sodium-dependent phosphate transport by parathyroid hormone in opossum kidney cells: adenosine 3',5'-monophosphate-dependent and -independent mechanisms.

The hormonal regulation of Na+-dependent phosphate transport was studied in opossum kidney (OK) cells. PTH caused time- and concentration-dependent decreases in Na+-dependent phosphate transport, with 10 pM PTH-(1-34) producing a 19% decline in phosphate transport. The EC50 for PTH inhibition of phosphate transport was 50 pM.

Species differences in the distribution of infracuticular F-actin in outer hair cells of the cochlea.

The distribution of filamentous actin (F-actin) in outer hair cells has been examined in several mammalian species using tetramethylrhodamine phalloidin, a specific marker for F-actin. The stereocilia and cuticular plates of the OHC in all species examined (pigmented guinea pig, hooded rat, chinchilla and squirrel monkey) contained F-actin; however, an infracuticular network of F-actin was present in OHC of the apical turns of the guinea pig cochlea but could not be identified in any other species examined.

Sound-induced artifact in cochlear blood flow measurements using the laser Doppler flowmeter.

The laser Doppler flowmeter has been shown to give a response from the cochlea during high intensity acoustic stimulation which is not related to blood flow through the cochlea. The magnitude of this response depends upon the intensity and frequency of stimulation and the location of the probe on the cochlea. Evidence is presented that the response is derived from the vibration of cochlear tissue and/or the bony cochlear shell during acoustic stimulation.

Monitoring guinea pig core temperature by telemetry during inhalation exposures.

A temperature telemetry system was incorporated into an existing animal model for inhalation toxicology. This system facilitated continuous monitoring of guinea pig temperature during inhalation exposures. Components of the system included Mini-Mitter temperature-controlled oscillators, AM receivers, and an IBM microcomputer.

A dual mechanism for regulation of kidney phosphate transport by parathyroid hormone.

Regulation of phosphate transport by parathyroid hormone (PTH) was investigated in continuous lines of kidney cells. Phosphate transport was reduced by PTH-(1-34) at physiological concentrations (EC50 5 X 10(-11) M), whereas much higher concentrations were required to stimulate cAMP formation (EC50 1 X 10(-8) M) in opossum kidney (OK) cells. The PTH analogue [Nle]PTH-(3-34) also inhibited phosphate transport but did not enhance cAMP formation.

Experimental sensitization to subtilisin. II. Production of specific antibodies following inhalation exposure of guinea pigs.

We have previously reported the development of pulmonary sensitivity in guinea pigs exposed for 5 consecutive days to bacterial subtilisin in concentrations ranging from 1.9 to 15.0 mg proteolytic enzyme/m3.

Back-scattered electron imaging of sections through the cochlea: a new technique for studying cochlear morphology.

A new technique for studying the morphology of the cochlea is described. The development of back-scattered electron (BSE) detectors has allowed the examination of heavy-metal stained tissues by scanning electron microscopy. Comparison with light microscopy on adjacent resin sections through whole decalcified cochleae demonstrated that the back-scattered electron technique provides equal or superior clarity and resolution throughout the light microscope range of magnification, allows identification of lysosomes, mitochondria and endoplasmic reticulum, and extends useful magnification into the range previously associated only with transmission electron microscopy.

Contact sensitivity by diisocyanates: potencies and cross-reactivities.

The dermal sensitizing potencies of four diisocyanates were investigated using the mouse ear-swelling test (MEST) with BALB/cBy mice. Mice were administered topical doses of diisocyanates to the abdomen and were challenged on the ear 4 days later with a nonirritating dose of chemical. The increase in ear thickness at 24 hr postchallenge indicated the extent of contact sensitivity.

Differences in the distribution of F-actin in outer hair cells along the organ of Corti.

There is evidence of differences in the structure, innervation and physiological responses between outer hair cells (OHCs) of the basal and apical turns of the mammalian cochlea. In this study we have used rhodamine-labelled phalloidin to investigate the differential distribution of F-actin in OHCs along the organ of Corti of the guinea pig. Isolated OHCs and surface preparations and cryosections of the organ of Corti were studied.

Effects of carbon monoxide on cochlear electrophysiology and blood flow.

The belief that the cochlea is particularly vulnerable to a reduction in oxygen availability comes predominantly from studies reporting the disruption of electrophysiological measures, such as the compound action potential, endocochlear potential, inner hair cell intracellular potentials or afferent nerve fiber responses by asphyxiation. Because hypoxia has frequently been suggested as an underlying mechanism by which many ototoxic agents produce injury, and because such agents are not likely to completely disrupt oxygen delivery, we investigated the effects of graded hypoxia (using doses of carbon monoxide) on cochlear blood flow, the compound action potential (CAP) and the cochlear microphonic (CM). High doses of carbon monoxide injected intra-peritoneally yielded reversible loss of the CAP sensitivity for high frequency tone bursts, the extent of which was dose dependent.

Laser Doppler measurements of cochlear blood flow during loud sound exposure in the guinea pig.

This investigation examined the effects of loud sound of different frequencies and intensities on cochlear blood flow as measured by the laser Doppler flowmeter. Cochlear blood flow was measured in anesthetized guinea pigs during a 1 h exposure to either a 2, 4, or 12 kHz pure tone or high-pass noise (10-40 kHz) at 90, 103, or 110 dB SPL. Cochlear function was assessed using the compound action potential audiogram before and after exposure.

Experimental sensitization to subtilisin. I. Production of immediate- and late-onset pulmonary reactions.

Four experiments were undertaken to explore the nature of pulmonary sensitivity which may result from inhalation of subtilisin aerosols. In the first study, immediate- and late-onset responses were identified. Groups of guinea pigs were exposed to atmospheres containing 0.

The pathogenesis of stereocilia abnormalities in acoustic trauma.

Stereocilia abnormalities develop in anesthetized guinea pigs within two minutes of exposure to loud sound (3 kHz, 125 dB SPL). Displacement, fracture, fusion and membrane rupture were observed well before the development (after 10 or more minutes) of fine structural changes to other cytoplasmic organelles within the hair cells. Thus stereocilia abnormalities can arise very rapidly due to the direct effects of noise on their microfilaments, cross linkages and limiting membranes.

Physicochemical characterization of cryogenically ground, size separated, fibrogenic particles.

A method for cryogenically grinding and separating (by size) fibrogenic minerals in the 1-micron size range is described and verified for chrysotile asbestos, quartz, forsterite (an olivine), and tantalum with a battery of analytical tests. Through use of energy dispersive X-ray spectroscopy, neutron activation analysis, X-ray photoelectron spectroscopy, and X-ray diffraction analysis it is shown that the grinding and separation procedure described does not alter the mineral composition, preserves the trace element composition, maintains the surface composition, and preserves the crystalline structure. Further, investigation of electrokinetic properties of these dusts by electrophoretic quasielastic light scattering is described.

Changing relationships between structure and function in the cochlea during recovery from intense sound exposure.

This study examines the relationship between the morphological and electrophysiological changes in the guinea pig cochlea at intervals following exposure to intense sound (5 kHz, 125 dB SPL, 30 minutes). The cochlear compound action potential (N1) audiogram (2-30 kHz) was determined within one hour or 1, 7, 14, or 28 days after exposure. When these organs of Corti were examined by scanning electron microscopy, most (92%) showed damage to hair cells and supporting cells around the 5-kHz region.

The accuracy of hair cell counts in determining distance and position along the organ of Corti.

The relationship between the density of hair cells (cells/mm) and measured distance along the guinea pig organ of Corti was determined using light microscopy and the surface specimen technique. It was demonstrated that the density of inner hair cells (IHC; mean 92.0 +/- 2.

A quantitative study of the sequence of topographical changes in the organ of Corti following acoustic trauma.

The organs of Corti of 30 guinea pigs were examined quantitatively by scanning electron microscopy either immediately or 1, 3, 7 or 14 days after exposure to 3 kHz at 125 dB SPL for 30 min. Lesions (0.1-4.

Animal chamber for in vivo testing of toxic gases.

A closed-circuit chamber system for exposing animals to toxic concentrations of oxygen or nitrogen was designed and built. The facility was equipped with systems for the removal of carbon dioxide, ammonia, methane, water vapor, and particulates from the gas stream. Integral systems were built to monitor and control temperature (+/- 1 degree C), relative humidity (+/- 2%), oxygen concentration (10 to 100% +/- 0.

A study in the relationship between emotional stability, intellectual ability, academic attainment, personal contentment and vocational aspirations.

This study investigated the relationship between ability, attainment and emotional stability, as measured by neuroticism, in underachieving, emotionally disturbed children. Forty children participated in four groups (mean age: 12.6, SD: 2.

Removal of metronidazole by haemodialysis.

The removal of the anti-anaerobic antibiotic metronidazole has been studied in oliguric patients. The drug and its principal metabolite are rapidly removed by haemodialysis so that the plasma concentration quickly falls below the therapeutic range. Hence a further dose of metronidazole would be needed after dialysis to restore an adequate plasma concentration.

Comparison of the pharmacokinetics of metronidazole in healthy female volunteers following either a single oral or intravenous dose.

The plasma pharmacokinetics of metronidazole following a single dose (500 mg) of metronidazole have been investigated in a crossover study in healthy female volunteers, using assays specific for metronidazole and its metabolites 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole (metabolite I) and 2-methyl-5-nitroimidazole-1-acetic acid (metabolite II). No systematic differences, which could be related to the route of metronidazole administration, were observed in the area under the plasma metronidazole concentration against time curve, elimination half-life, apparent volume of distribution, or total urinary excretion of metronidazole. Following a single oral or intravenous dose, the half-life estimates were 7.

Cytokinetic analysis of the impaired proliferative response of peripheral lymphocytes from aged humans to phytohemagglutinin.

The effect of donor age on the rate of cell entry into the proliferating pool and subsequent cell cycle duration for peripheral lymphocytes stimulated by phytohemagglutinin (PHA) were examined by using the bromodeoxyuridine incorporation-differential staining technique. Distribution curves for the appearance of metaphase cells in successive generations as a function of culture time were obtained and analyzed both graphically and by a computer simulation model. Peripheral lymphocytes from aged individuals (approximately 75 yr) were stimulated by PHA at approximately one-half of the rate of peripheral lymphocytes from young individuals (approximately 21 yr).

BISACK analysis of the phytohaemagglutinin-induced proliferation of human peripheral lymphocytes.

The rate of stimulation as well as subsequent cell cycle duration was examined in phytohaemagglutinin-stimulated human peripheral lymphocytes grown in vitro in the presence of non-inhibotory concentrations of bromodeoxyuridine. After incorporation of this heavy atom analogue of thymidine into replicating cellular DNA, it was possible to identify unequivocally metaphase cells which had replicated for one, two and three or more cells cycles. Utlizing this technique, distribution curves were obtained for the appearance of metaphase cells in successive generations, were analysed by a computer simulation model, and the rate of stimulation (4.