The time-course of the effects of contralateral sound on the level of distortion product otoacoustic emissions.

The effects of the addition of contralateral noise on the level of distortion product otoacoustic emissions (DPOAEs) were examined. In the present study, the DPOAEs were recorded for a relatively long period (2 minutes), and the time-course of the effects of contralateral sound on the level of DPOAEs were considered. In general, the addition of the contralateral noise resulted in suppression of the level of DPOAEs. The time-course of this suppression appeared to depend on the level of the contralateral noise. When the level of the contralateral noise was low, the suppression of the level of DPOAEs seemed to be largely unchanged for at least 2 minutes. In contrast, when a relatively high level of contralateral noise was used, the suppression of the level of DPOAEs decreased with time.

Possible regulation of epidermal growth factor-receptor tyrosine autophosphorylation by calcium and G proteins in chemically permeabilized rat UMR106 cells.

A model using chemically permeabilized cells was developed to examine mechanisms that regulate protein tyrosine phosphorylation in osteoblastic cells. Using either permeabilized UMR106 osteoblastic or A431 (reference) cells, epidermal growth factor (EGF)-induced cellular tyrosine phosphorylation, and whether there are previously unrecognized interactions between this transduction pathway and Ca2+- or G protein-dependent signalling pathways, were investigated. Both permeabilized cell types, when maintained in non-supplemented cytoplasmic substitution solution (basic CSS), responded to EGF (1-100 ng/ml) with dose-dependent increases in tyrosine phosphorylation. A complex and time-dependent pattern of phosphotyrosine-containing proteins resulted, but the profile of tyrosine phosphorylated proteins was appreciably less complex than in intact cells. Supplementation of basic CSS with MgATP restored the normal complexity of the profiles for EGF-induced tyrosine phosphorylation proteins in both permeabilized cell lines and produced a more sustained accumulation of phosphoprotein products in A431 cells. Adding Ca2+ (< or = 10(-6) M), with or without exogenous MgATP, dose-dependently attenuated EGF-induced tyrosine phosphorylation of EGF receptors (EGFR) and other substrates in UMR106 cells, but was less effective in A431 cells. In both cell types, genistein, an inhibitor of tyrosine kinases, was more effective in attenuating EGF-induced receptor tyrosine phosphorylation in permeabilized cells. Similarly, orthovanadate, an inhibitor of protein tyrosine phosphatases, stimulated the accumulation of phosphoprotein products more effectively in permeabilized cells. Thus, the permeabilization preserves many features of intact cells while facilitating manipulation of intracellular conditions. NaF reproducibly produced a significant vanadate-like action in permeabilized cells that was somewhat stronger than its effect on intact cells. In contrast, the well-known inhibition of tyrosine phosphorylation by phorbol 12-myristate 13-acetate (PMA) was less effective in permeabilized cells than in intact cells; these actions of PMA were Ca2+-dependent. In addition, guanylyl-imidodiphosphate (Gpp(NH)p) attenuated tyrosine phosphorylation in UMR106 cells, and this effect was specifically blocked by guanosine 5'-O-(2-thiodiphosphate) (GDPbetas). These results strongly suggest that there is crosstalk between EGFR-activated tyrosine phosphorylation/dephosphorylation pathways and both Ca2+- and G protein-mediated pathways in UMR106 cells, revealing a previously unrecognized modulation of EGF signalling in osteoblast-like cells that contrasts with the simpler regulatory mechanisms found in A431 cells.

Frequency summation observed in the human acoustic reflex.

It is known that the threshold of an acoustically induced middle-ear-muscle (MEM) reflex can be lowered by the simultaneous presentation of a second tone (facilitator), which is presented to the ipsilateral or contralateral ear at a level below the acoustic reflex threshold (ART) of the facilitator itself (Sesterhenn and Breuninger, 1976; Blood and Greenberg, 1981). In the present study, a primary elicitor and a facilitator were presented to the ear contralateral to that used for measurement of the acoustic reflex (AR), and the effects of changing frequencies and sound levels of the facilitator were investigated in human subjects with normal ears. The sound levels of facilitators, which caused a significant reduction of ART for the primary elicitors (facilitation thresholds), showed an asymmetrical pattern as a function of frequency of the facilitators. The facilitation thresholds tended to be lower when a facilitator with a frequency lower than the frequency of the elicitor (1 kHz) was used. In addition, effects of the elicitor on the masked thresholds of the facilitator were examined to observe the possible interaction between elicitor and facilitator from the viewpoint of 'spread of excitation'. The underlying mechanism of summation effects of two tones are discussed based on the possible input mechanism involved in the acoustically induced MEM reflex are.

Antimasking effects of the olivocochlear reflex. I. Enhancement of compound action potentials to masked tones.

1. The effects of olivocochlear (OC) feedback on signal processing in the cochlea were studied by comparing responses seen with and without a contralateral noise or by comparing responses seen before and after cutting the OC bundle (OCB). Adding and subtracting a contralateral noise is a convenient, reversible way of changing the level of OC feedback; however, it fully reveals only the contribution of the contralaterally responsive efferent fibers. Cutting the OCB can reveal the full contribution of all fibers in the OCB; however, the manipulation can only be performed once per experiment. 2. The amplitude of the compound action potential (CAP), recorded from anesthetized or decerebrate cats in response to tone pips, could be increased by addition of contralateral noise at moderate sound pressure levels. These enhancement phenomena were most easily demonstrable when the tone pips were masked by ipsilateral broadband noise; however, in some animals CAP enhancement was seen in the absence of ipsilateral maskers. Enhancement-in-quiet may arise because of internal masking from animal-generated noise. All contralateral-noise enhancement disappeared when the OCB was cut. 3. Enhancement effects of contralateral noise could be seen in both simultaneous and forward-masking paradigms. Enhancement was largest for high-frequency tone pips (8-16 kHz) and could be demonstrated over a wide range of tone-pip levels and ipsilateral-masker levels. Suppression of CAP by the contralateral noise was often seen for lower tone-pip frequencies (2-8 kHz) and lower tone-pip intensities. These trends may be understood in the context of known properties of OC peripheral effects and known properties of physiological masking. 4. Cutting the OCB resulted in a decrease in CAP amplitudes to masked tone pips. When CAP was measured to tone pips presented in equilevel, binaural noise, OCB section resulted in a decrease in CAP amplitudes equivalent to at least a 6-dB decrease in signal-to-noise ratio. Such antimasking effects of an intact OCB were seen in both simultaneous and forward-masking paradigms. 5. Present evidence suggests that all these antimasking effects can be explained on the basis of activation of the medial OC fibers to the outer hair cells. By suppressing responses to continuous noise backgrounds, the OC reflex may enhance responses to transient masked stimuli by decreasing the level of adaptation in auditory nerve fibers. Such effects of the OC reflex should improve discrimination of transient signals presented in a continuous noise background.

Induction of macrophagic and granulocytic differentiation of murine bone marrow progenitor cells by 1,25-dihydroxyvitamin D3.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) was recently shown to promote maturation of 5-fluorouracil (5FU)-treated bone marrow cells by up-regulating macrophage-colony stimulating factor (M-CSF) receptors in the presence of interleukin 1 alpha (IL-1 alpha). In order to reveal how 1,25(OH)2D3 interacts with colony-stimulating factors and regulates the differentiation of bone marrow progenitor cell populations, in the present study, natural bone marrow cells were isolated from untreated mice and used in alpha-minimum essential medium supplemented with 20% heat-inactivated horse serum without added appropriate cytokines. Under the conditions, cells spontaneously differentiated gradually with days of culture, as assessed by expression of macrophage differentiation antigens such as Mac-1 (CD11b) and F4/80. Both M-CSF and granulocyte macrophage-colony stimulating factor (GM-CSF) induced only Mac-1 antigen expression. Simultaneous treatment with M-CSF and 1,25(OH)2D3 enhanced the M-CSF's effect on expression of both antigens, although 1,25(OH)2D3 per se has no effect on the expression for up to 11 days. In addition, successive treatment with 1,25(OH)2D3 and M-CSF or GM-CSF dramatically enhanced expression of both antigens or Mac-1 antigen, respectively. Similarly, both simultaneous and successive treatment with 1,25(OH)2D3 and M-CSF significantly enhanced phagocytic activity and H2O2 production, whereas successive treatment with 1,25(OH)2D3 and GM-CSF significantly enhanced only phagocytic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Reversibility of energy metabolism and intracellular pH after cerebral ischaemia evaluated by 31P-MRS.

We have previously developed a reproducible model of transient forebrain ischaemia in rats by bilateral carotid artery occlusion combined with temporary increase of ICP. With this model, reversibility of the energy metabolism and intracellular pH (pHi) was investigated by 31P-MRS during 120 min of recirculation in three groups of, respectively, 30, 60, and 120 min of ischaemia. With the induction of ischaemia, ATP and phosphocreatine (PCr) disappeared, and measurement of pHi showed severe acidosis in all rats. In the 30 min ischaemia group, both energy metabolism and pHi recovered almost completely. In the 60 min ischaemia group, ATP recovered to 74% of control values, but pHi showed full recovery. In the 120 min ischaemia group, ATP recovered to about 50% of control values, and recovery of pHi was variable. Showing logarithmical changes during recirculation in ATP and PCr, the rate of metabolic recovery was fast during 60 min of recirculation, but it decreased and reached plateau thereafter in all groups. Recovery of pHi was affected by ATP levels, and was precipitously accelerated as ATP levels exceeded 50% of pre-ischaemic values. These results suggest that prolongation of the duration of ischaemia limits the restoration of the energy state, and the quality of pHi recovery after cerebral ischaemia is affected by the degree of ATP recovery during 60 min of recirculation.

Cholestatic hepatocellular carcinoma diagnosed by deposits of Lipiodol and treated by combination of endoscopic retrograde biliary drainage and transcatheter arterial embolization.

Cholestatic hepatocellular carcinoma, which grows into the bile duct and causes obstructive jaundice, is rare and difficult to diagnose. A case is presented in which cholestatic hepatocellular carcinoma was detected by deposit of Lipiodol. This is also the first case that was successfully treated by endoscopic retrograde biliary drainage and transcatheter arterial embolization.

Modulation of hepatotoxicity by macrophages in the liver.

In an attempt to elucidate the role of hepatic macrophages in liver injury, we investigated galactosamine-treated rats (500 mg per kg body weight). The rats received an i.v. injection of latex particles (2 x 10(9) particles per animal) prior to (latex-galactosamine) or 12 to 16 hr subsequent to the galactosamine treatment (galactosamine-latex). Effect of superoxide dismutase on hepatic injury induced by galactosamine or galactosamine-latex treatment was also examined. Oxygen-derived free radical-generating capacity of isolated hepatic macrophages was measured as chemiluminescence with the stimulation of phorbol myristate acetate or latex particles. As compared with normal rats, chemiluminescence of hepatic macrophages from galactosamine-treated rats was 5- to 10-fold enhanced 12 hr following galactosamine treatment and remained elevated for 48 hr. Chemiluminescence of the latex particle-pretreated macrophages in the liver was markedly suppressed even following the galactosamine treatment (p less than 0.01). Compared to galactosamine-treated rats, both lipid peroxide level in the liver tissue and AST and ALT concentration in serum were significantly decreased in the latex-galactosamine-treated rats (p less than 0.01) and increased in the galactosamine-latex-treated rats (p less than 0.01). Furthermore, superoxide dismutase supplementation protected against liver injury induced by the galactosamine-latex treatment. From these results, pretreatment with latex particles suppressed the free radical-generating capacity of hepatic macrophages and protected against hepatic injury induced by galactosamine. In contrast, injection of latex particles after galactosamine treatment aggravated hepatic injury, which was prevented by superoxide dismutase. These data suggest that liver injury induced by galactosamine is modulated by oxygen-derived free radicals from hepatic macrophages.