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PubMed1990

Long peritoneal lavage decreases pancreatic sepsis in acute pancreatitis.

Late infection of devitalized pancreatic and peripancreatic tissue has become the major cause of morbidity in severe acute pancreatitis. Previous experience found that peritoneal lavage for periods of 48 to 96 hours may reduce early systemic complications but did not decrease late pancreatic sepsis. A fortunate observation led to the present study of the influence of a longer period of lavage on late sepsis. Twenty-nine patients receiving primary nonoperative treatment for severe acute pancreatitis (three or more positive prognostic signs) were randomly assigned to short peritoneal lavage (SPL) for 2 days (15 patients) or to long peritoneal lavage (LPL) for 7 days (14 patients). Positive prognostic signs averaged 5 in both groups but the frequency of five or more signs was higher in LPL (71%) than in SPL (47%). Eleven patients in each group had early computed tomographic (CT) scans. Peripancreatic fluid collections were shown more commonly in LPL (82%) than in SPL (54%) patients. Longer lavage dramatically reduced the frequency of both pancreatic sepsis (22% LPL versus 40% SPL) and death from sepsis (0% LPL versus 20% SPL). Among patients with fluid collections on early CT scan, LPL led to a more marked reduction in both pancreatic sepsis (33% LPL versus 83% SPL) and death from sepsis (0% LPL versus 33% SPL). The differences were even more striking among 17 patients with five or more positive prognostic signs. In this group the incidence of pancreatic sepsis was 30% LPL versus 57% SPL and of death from sepsis 0% (LPL) versus 43% (SPL) (p = 0.05). In these patients, overall mortality was also reduced (20% LPL versus 43% SPL). When 20 patients treated by LPL were compared with 91 other patients with three or more positive prognostic signs who were treated without lavage or by lavage for periods of 2 to 4 days, the frequency of death from pancreatic sepsis was reduced from 13% to 5%. In those with five or more signs, the incidence of sepsis was reduced from 40% to 27% (p = 0.03) and of death for sepsis from 30% to 7% (p = 0.08). These findings indicate that lavage of the peritoneal cavity for 7 days may significantly reduce both the frequency and mortality rate of pancreatic sepsis in severe acute pancreatitis.

Abscess↗
PubMed1997

Auditory cortical onset responses revisited. II. Response strength.

Most neurons of the auditory pathway discharge spikes locked to the onset of an acoustic stimulus, but it is largely unknown in which way the acoustic parameters of sound onsets shape the neuronal responses. In this paper is analyzed the number of spikes discharged by single neurons in primary auditory cortex of barbiturate-anesthetized cats to the onsets of tones of characteristic frequency. The time course of the peak pressure (i.e., the envelope) was altered by parametrically varying sound pressure level (SPL), rise time, and rise function (linear or cosine-squared). For both rise functions, rise time had manifold, and in some cases dramatic, effects on conventional spike count-level functions. In general, threshold SPL, dynamic range, and the lowest SPL at which monotonic spike count functions saturated increased with prolongation of the rise time. In neurons with mostly nonmonotonic spike count-level functions, "best SPL" increased and the descending high-SPL arms flattened, so that functions obtained with long rise times were often monotonic whereas those obtained with shorter rise times were highly nonmonotonic. Consequently, the "tuning" to SPL was less sharp for longer rise time tones, and spike count versus rise time functions changed from "short-pass" to "long-pass" with an increase in SPL. Systematic effects of rise time persisted when spike counts were plotted against the rate of change of peak pressure or against the maximum acceleration of peak pressure. However, when spike counts were plotted as a function of the instantaneous peak pressure at the time of response initiation, the functions obtained with different rise times, and even with different rise functions, were in close register. This suggests that the stimulus-dependent component of first-spike latency can be viewed as an integration window, during which rate of change of peak pressure is integrated. The window commences with tone onset and its duration is inversely related to the maximum acceleration (or, for linear rise functions, the rate of change) of peak pressure and the neuron's transient sensitivity. The present findings seriously question, for onset responses, the usefulness of the spike count-level function and measures derived from it, such as threshold SPL, dynamic range, best SPL, or degree of nonmonotonicity. They further cast doubt onto the validity of current concepts of intensity coding at cortical levels, because most neurons' onset responses are not indicative of a signal's steady-state SPL. However, they suggest a mechanism by which a neuronal population will sample a given transient in an orderly, sensitivity-dependent, temporal sequence. The sampling rate is automatically adjusted to, and adjusted by, the rapidity of the signal's change. And the instantaneous properties of the transient could be represented by the ratios and spatial distribution of responses across the simultaneously active subpopulation. Such a mechanism could provide the basis for the demonstrated capability of discrimination of rapid transients.

Animals↗
PubMed1997

Complications associated with use of a one-hole subpalpebral lavage system in horses: 150 cases (1977-1996).

OBJECTIVE: To determine type and frequency of complications associated with use of a one-hole subpalpebral lavage (SPL) system in horses. DESIGN: Retrospective study. ANIMALS: 150 horses with 156 SPL systems. PROCEDURE: Signalment, primary complaint, method used for placement, time SPL system was in place, and complications were retrieved from medical records. RESULTS: Complications were not associated with placement, maintenance, or removal of 66 of 156 (42%) SPL systems. A minor complication was reported in association with 53 (34%) SPL systems, and a serious complication was reported in association with 37 (24%). The 3 most common minor complications were mild swelling of the eyelid (31 horses), tearing of SPL system tubing (20), and loss of the injection cap (30). Serious complications included problems with the SPL system requiring its premature removal and possible replacement (26 horses), removal of the SPL system by the horse (6), infection of the eyelid (4), loss of the footplate in the eyelid (5), and cornea ulceration (1). CLINICAL IMPLICATIONS: Proper attention to the size of the footplate and placement of the SPL system in the eyelid should decrease the risk of serious complications. Minor eyelid swelling should be expected in the first 48 hours after SPL system placement.

Animals↗
PubMed1997

Cytochrome P450 2C11: Escherichia coli expression, purification, functional characterization, and mechanism-based inactivation of the enzyme.

The male-specific P450 enzyme CYP 2C11, whose expression is developmentally and hormonally regulated, is the major steroid 16alpha-hydroxylase of the untreated rat liver. The enzyme metabolizes a host of substrates, including mechanism-based inactivators, such as 3,5-dicarbethoxy-2,6-dimethyl-4-ethyl-1,4-dihydropyridine (DDEP) and spironolactone (SPL). Structural and functional characterization of the specific mode of such inactivation, however, requires sufficient quantities of the fully purified enzyme. Although several laboratories including our own have isolated and purified the enzyme from male rats, the yields are typically low and of the order of 1%. For these reasons, we chose to heterologously express the enzyme in Escherichia coli. The full-length cDNA was excised from the yeast vector pD2M1 and cloned into the plasmid vector pCW after appropriate modifications for optimal expression in E. coli. The enzyme was isolated and purified from E. coli membranes in relatively high yields (approximately 60%) and relatively high specific content (19 nmol/mg protein). The purified recombinant enzyme had spectral and functional characteristics comparable to those reported for the native rat liver enzyme, including mechanism-based inactivation by DDEP and SPL. Studies with 14C-heme-labeled enzyme indicated that the major mode of DDEP inactivation was via heme-N-ethylation. On the other hand, studies with radiolabeled SPL-SH (the proximal inactivating deacetylated metabolite of SPL) revealed that although both [22-14C]SPL-SH and SPL-35SH inactivated the enzyme, only SPL-35SH was found to irreversibly radiolabel the 2C11 protein. The latter findings thus suggest that during mechanism-based inactivation of 2C11, the thiol moiety of SPL-SH is oxidatively activated to a species that attacks the 2C11 protein during or after cleavage from the thiosteroid. Thus, these modes of mechanism-based 2C11 inactivation by DDEP and SPL-SH considerably differ from the corresponding modes of P450 3A inactivation by these agents, wherein heme modification of the protein predominates.

Amino Acid Sequence↗
PubMed2000

Avian dependence on sound pressure level as an auditory distance cue.

Sound pressure level (SPL) has received little attention as a distance cue or signal for communication because of the methodological difficulty of determining source SPL from free-ranging signallers and because SPL is presumed to be unreliable as a distance cue. Eastern towhees, Pipilo erythrophthalmus (Emberizidae, Passeriformes), in south-central Florida give a simple call during territorial interactions. I obtained measurements of call-source SPL with a calibrated microphone positioned 100+/-10 cm from caged male eastern towhees. Measurements of source SPL were highly variable, but much of this variation can be predicted from measurements of call duration or call frequency variables (spectrotemporal variables). Male towhees accurately perceived the distance of a speaker after it played synthetic calls that matched the amplitude and structure of natural 84-dB and 78-dB call types. Subjects flew further in response to an attenuated (-6 or -12 dB) version of an otherwise identical 84-dB call and flew shorter in response to an amplified (+6 dB) version of this same call. Towhees misjudged speaker distance in approximately half of the trials that included a discrepancy (-6, -12 or +6 dB SPL) between playback source SPL and predicted spectrotemporal variables. These distance errors suggest that towhees assess auditory distance partly from the difference between perceived SPL and source SPL, determined from spectrotemporal variables. Copyright 2000 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1979

Biofeedback control of skin potential level.

This study explored the possibility of using biofeedback to arrest spontaneous declines in tonic electrodermal levels. For 3 days, 10 subjects (S) received 20 minutes of training in increasing skin potential level (SPL) negativity (arrested declines), followed by 20 minutes of training in decreasing SPL negativity (facilitating declines), with reverse order for half of the Ss. Simultaneous analogue and binary feedback of SPL were used. Training in the direction of SPL increases resulted in arrest of spontaneous declines in SPL negativity but did not result in large-magnitude increases above baseline. Training in the direction of SPL decreases facilitated declines in SPL. The absolute mean difference between the increase condition and the decrease condition on the 3rd day was 8.28 mV. Correlations suggested that considerable intraindividual variability may have been independently related to the Locus of Control personality dimension and to a Law of Initial Values limitation on SPL change. It was concluded that SPL was controllable to the extent of facilitating or arresting spontaneous declines.

Action Potentials↗
PubMed1997

[Hearing tests in extended high frequency range in pre-school age children. Initial results].

Since reliable headphones are now available, clinical audiometry can also be performed in extended high frequencies (EHF). Hearing in frequencies over 10 kHz is more influenced by age, noise and toxicity. Thus it is useful to take additionally results in children to establish the normal hearing threshold. In the present study, 35 pre-school children (ages 4-7 years) were tested by EHF (8 kHz-16 kHz) using a new Sennheiser HDA-200 headphone. The hearing thresholds recorded corresponded to those of other studied. Median and standard deviations for 10 kHz were 25 dB(SPL) +/- 12 dB(SPL), 35 dB(SPL) +/- 12 dB(SPL) for 12.5 kHz and 50 dB(SPL) +/- 15 dB(SPL) for 16 kHz. In the older children (> 5 years), hearing thresholds could be more reliably determined and were 10 dB(SPL) better than in the younger children (< 5 years). Thresholds at 10 kHz-12.5 kHz corresponded to those found in adults, but were more sensitive by 5 dB(SPL)-15 dB(SPL) in the 14 kHz-16 kHz range.

Adult↗
PubMed2006

Subclinical pregnancy losses among women undergoing in-vitro fertilization with ICSI.

BACKGROUND: The purpose of this study is to asses the frequency of subclinical pregnancy loss (SPL) among women undergoing controlled ovarian hyperstimulation (COH) and in-vitro fertilization with ICSI. METHODS: The study was retrospectively conducted in a private IVF center. SPL was defined by a temporary rise in serum beta hCG, along with the absence of signs of intra- and extra-uterine pregnancy by transvaginal ultrasonography. Overall 5273 COH and ICSI cycles with embryo transfer (ET) were segregated according to serum E(2) levels percentiles (-24th, 25th, 74th, and 75th), women age and the type of spermatozoa for assisted fertilization (ejaculated and surgically retrieved). Those groups were assessed for SPL rates. RESULTS: Among the 3125 (59.25) conception cycles, 305 (9.7%) were diagnosed as SPL. There was no difference in SPL rate among E(2) percentile groups. Women older than 35 years of age had significantly higher rate of SPL compared to younger women. There was also no difference in SPL rate among pregnancies in whom surgically retrieved spermatozoa used or ejaculated spermatozoa used for assisted fertilization. CONCLUSION: Our results demonstrated that SPL rate was not influenced by the levels of E(2) during COH or the origin of spermatozoa used for assisted fertilization. However, maternal age was found to be detrimental for SPL.

Abortion, Spontaneous↗
PubMed2004

How prevalent is hyperkalemia and renal dysfunction during treatment with spironolactone in patients with congestive heart failure?

BACKGROUND: Treatment with spironolactone (SPL) is beneficial in patients with severe congestive heart failure (CHF). In the Randomized Aldactone Evaluation Study SPL was well tolerated, particularly with regard to renal function and serum K(+) levels. Our aim was to investigate whether the reported low frequency of adverse effects during SPL treatment in a heart failure study population could be confirmed in an unselected heart failure outpatient cohort and to identify potential predictors of harmful effects. METHODS AND RESULTS: We investigated 125 consecutive patients with CHF recruited from our heart failure clinic. Inclusion criteria were LVEF (left ventricular ejection fraction) </=45% and treatment with SPL. Blood tests were performed bimonthly or more frequently if necessary. Outcomes measures were (1) increases in serum K(+) to >5,0, 5.5, 6.0, or 6.5 mmol/L, respectively, and (2) rise in serum creatinine to 120%, 150%, and 200% of baseline, respectively. Mean age was 72.9 years (range 46.5 to 90.6 years); 27% were women. The New York Heart Association class distribution was: I, 6%; II, 44%; III, 46%; and IV, 4%. Mean LVEF was 29+/-5%. Other medication included angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in 86% and beta-blockers in 39%. At baseline, serum creatinine levels were 117.6+/-6.5 (mean+/-standard deviation; micromol/L, normal <130) and serum K(+) was 4.2+/-0.3 mmol/L. The mean follow-up period was 11 months, and the cumulative observation period was 73 SPL treatment years. Mean peak serum-creatinine was 167.6 micromol/L+/-11.9 (45% increase from baseline) and mean peak serum K(+) was 5.0+/-0.4 mmol/L (21% increase from baseline). Sixty patients were already on SPL when admitted to the CHF clinic. The remainder were initiated on SPL. During the follow-up period 36% of the patients developed hyperkalemia (>5 mmol/L), with 10% having serum K(+) >6 mmol/L. An increase in serum creatinine of >20% was seen in 55%, and in 24% an increase of >50% was found. These alterations in serum creatinine and serum K(+) were not significantly more frequent in patients treated with angiotensin-converting enzyme inhibitors or beta-blockers or different doses of SPL. CONCLUSION: SPL adverse effects (impaired renal function, increase in serum K(+)) are much more prevalent in our elderly CHF patient population than previously reported. The recommendations from our study are that (1) particular caution is mandated in elderly patients with an LVEF <20%, (2) potassium supplementation should be discontinued, (3) changes in body weight should raise concern, and (4) a dose-adjustment of the concomitant conventional diuretic regime should be considered. Care should be given to the frequent monitoring of electrolytes and renal parameters.

Aged↗
PubMed1989

Oxidative metabolism of spironolactone: evidence for the involvement of electrophilic thiosteroid species in drug-mediated destruction of rat hepatic cytochrome P450.

In a preliminary paper [Decker et al. (1986) Biochem. Biophys. Res. Commun. 136, 1162] we have shown that the antimineralocorticoid spironolactone (SPL) preferentially inactivates dexamethasone (DEX) inducible rat hepatic cytochrome P450p isozymes in a suicidal manner. These findings are now confirmed, and the kinetic characteristics of such a process are detailed. In an effort to elucidate the mechanism of SPL-mediated inactivation of cytochrome P450, we have examined the metabolism of SPL in vitro. Incubation of [14C]SPL and NADPH with liver microsomes prepared from DEX-pretreated rats results in the formation of several polar metabolites separable by HPLC with UV detection. This process is found to be dependent on NADPH, O2, SPL, and enzyme concentration, as well as temperature. Furthermore, metabolite formation was significantly attenuated by P450 inhibitors CO and n-octylamine. Mass spectral analysis (thermospray LC/MS, FAB/MS, and FAB/MS/MS) of the two most prominent polar metabolites indicated that these compounds had molecular weights that corresponded to the sulfinic and sulfonic acid derivatives of deacetyl-SPL (SPL-SH). These findings document the formation of previously unreported polar metabolites of SPL by rat liver microsomes enriched in cytochrome P450p and implicate a role for this isozyme in the oxidation of the thiol moiety of deacetyl-SPL. The detection of such metabolites also implicates a catalytic trajectory that includes the thiyl radical and/or sulfenic acid species as a plausible protagonist in drug-mediated inactivation of cytochrome P450p.

Animals↗
PubMed1998

Effects of varied vocal intensity on ventilation and energy expenditure in women and men.

This study was completed to determine how ventilatory responses change by means of speech reading at three different sound pressure levels (SPL) as compared to quiet breathing prior to each task. The energy required to alter SPL was also studied and compared to energy expenditures during a quiet breathing condition. Twenty-four adults (12 women, 12 men) were studied while reading a standard passage at low, comfortable, and high SPLs for 7 minutes with quiet breathing periods between each task to achieve respiratory steady state and serve as a control to which the reading tasks were compared. The last 2 minutes of exhaled air for all speaking and quiet breathing tasks were collected using a Hans Rudolph mouth breathing face mask. A Sensor Medics Vmax 29 series diagnostic instrument system measured all ventilatory responses and energy expenditures. Volume and timing alterations in ventilation were characterized by measuring tidal volume (V[T]), inspiratory time (T[I]), inspiratory flow rate (V[T]/T[I]), and expiratory time (T[E]). Average ventilation, energy expenditure, and adequacy of ventilation were measured using minute ventilation (V[E]), oxygen consumption (VO2), carbon dioxide production (VCO2), and partial pressure of end-tidal carbon dioxide (end-tidal PET[CO2]). Results indicated volume, timing, ventilation, and energy expenditure values remained closest to quiet breathing values for the comfortable SPL. Volume, ventilation, and energy expenditure were significantly greater for the high SPL and lower for the low SPL, compared to the baseline steady state, indicating that the low SPL causes a ventilatory deficit that was found to be paid back at the end of the speech task during the quiet breathing period. These results demonstrate that an individual's comfortable SPL is the least energy-requiring way to speech breathe. As SPL rises above or below comfortable SPL, speech breathing requires more energy.

Adolescent↗
PubMed1989

Benzo[a]pyrene-induced immunotoxicity: comparison to DNA adduct formation in vivo, in cultured splenocytes, and in microsomal systems.

Benzo[a]pyrene (BaP)/DNA adduct formation appears to be involved in carcinogenesis, but the relationship between adduct formation and BaP-induced immunotoxicity is unknown. We compared DNA adduct formation (32P-postlabeling analysis) to suppression of polyclonal immune responses (3H-TdR incorporation and IgM secretion) and decreases in cell viability in B6C3F1 female mouse splenic leukocytes (SPL). BaP administration (200 mg/kg, ip) resulted in suppression of polyclonal responses and substantial DNA adduct formation in mouse SPL. SPL adduct levels were similar to those in liver, lung, kidney, and stomach. In vitro exposure of SPL to BaP without rat liver activation enzymes (S9) caused decreases in SPL viability and immune responses that were dependent on dose and exposure period. However, DNA adduct formation in SPL was very low between 1 and 200 microM BaP. S9 enhanced the toxicity of BaP for SPL cultures. Adduct formation was rapid and dose related in +S9 incubates. The low level of BaP activation by SPL was confirmed in microsomal incubations in which splenic microsomes exhibited much lower aryl hydrocarbon hydroxylase (AAH) activity and ability to form DNA-adducting metabolites than did microsomes from liver or lung. Results indicate that immunosuppression produced by BaP in these systems was due to cytotoxic effects. It appears that these effects were caused by two separate mechanisms, one dependent on and one independent of DNA adduct formation. Since SPL had high levels of DNA adducts after ip injection of BaP, reactive metabolites of BaP may be involved in the immunotoxicity seen in vivo.

Animals↗
PubMed1994

Temporal regulation and forespore-specific expression of the spore photoproduct lyase gene by sigma-G RNA polymerase during Bacillus subtilis sporulation.

Bacterial spores are highly resistant to killing by UV radiation and exhibit unique DNA photochemistry. UV irradiation of spore DNA results in formation of spore photoproduct (SP), the thymine dimer 5-thyminyl-5,6-dihydrothymine. Repair of SP occurs during germination of Bacillus subtilis spores by two distinct routes, either by the general nucleotide excision repair (uvr) pathway or by a novel SP-specific monomerization reaction mediated by the enzyme SP lyase, which is encoded by the spl gene. Repair of SP occurs early in spore germination and is independent of de novo protein synthesis, suggesting that the SP repair enzymes are synthesized during sporulation and are packaged in the dormant spore. To test this hypothesis, the expression of a translational spl-lacZ fusion integrated at the spl locus was monitored during B. subtilis growth and sporulation. beta-Galactosidase expression from the spl-lacZ fusion was silent during vegetative growth and was not DNA damage inducible, but it was activated at morphological stage III of sporulation specifically in the forespore compartment, coincident with activation of expression of the stage III marker enzyme glucose dehydrogenase. Expression of the spl-lacZ fusion was shown to be dependent upon the sporulation-specific RNA polymerase containing the sigma-G factor (E sigma G), as spl-lacZ expression was abolished in a mutant harboring a deletion in the sigG gene and restored by expression of the sigG gene in trans. Primer extension analysis of spl mRNA revealed a major extension product initiating upstream from a small open reading frame of unknown function which precedes spl, and it revealed two other shorter minor extension products. All three extension products were present in higher quantities during sporulation and after sigG induction. The three putative transcripts are all preceded by sequences which share homology with the consensus sigma-G factor-type promoter sequence, but in vitro transcription by purified sigma-G RNA polymerase was detected only from the promoter corresponding to the major extension product. The open reading frame-spl operon therefore appears to be an additional member of the sigma-G regulon, which also includes as members the small, acid-soluble spore proteins which are in large part responsible for spore DNA photochemistry. Therefore, sporulating bacteria appear to coordinately regulate genes whose products not only alter spore DNA photochemistry but also repair the major spore-specific photoproduct during germination

Amino Acid Sequence↗
PubMed1996

Responses of auditory nerve fibers of the unanesthetized decerebrate cat to click pairs as simulated echoes.

1. To elucidate the peripheral contribution to "echo" processing in the auditory system, we examined the characteristics of auditory nerve responses to click-pair stimuli in unanesthetized, decerebrate cats. We used equilevel click pairs at peak levels of 45, 65, and 85 dB SPL re 20 microPa. The interclick intervals ranged from 1 to 32 ms. This study reports results from 78 auditory nerve fibers in 7 cats. The fibers were divided into 2 groups: 33 low- and 45 high-spontaneous rate (SR), with SRs less than and > or = 20 spikes/s, respectively. A method was introduced to quantify the second-click response, and its recovery was examined as a function of the interclick interval. 2. In general, auditory nerve fibers showed a gradual recovery of the second-click response as interclick interval was increased. Noticeable differences in the second-click response recovery functions emerged among fiber populations that were related to the SR. Low-SR fibers showed little change in the recovery functions of the second-click response as the click level was increased from 45 to 85 dB SPL. In contrast, high-SR fibers showed slower recoveries with increasing click level from 45 to 85 dB SPL. At 45 and 65 dB SPL, the recovery functions of the two SR groups were similar. At 85 dB SPL, high-SR fibers exhibited slower recovery than low-SR fibers, regardless of fiber characteristic frequency. The interclick intervals at 50% second-click response ranged from 1 to 6 ms (mean, 1.4 ms) among low-SR fibers. The interclick intervals at 50% second-click response for high-SR fibers, whereas similar to those for the low-SR fibers at 45 and 65 dB SPL, ranged from 2 to 16 ms (mean, 3 ms) for high-SR fibers, at 85 dB SPL. 3. We also examined auditory nerve compound action potentials (CAPs) evoked by click-pair stimuli for various interclick intervals and click levels. With increasing interclick interval, the amplitude of the second-click CAP increased, and with increasing level, the second-click CAP showed slower recovery. At 45 dB SPL, the recovery functions of the second-click CAP were similar to those of the high- and low-SR fibers. At higher levels, the CAP exhibited lower second-click response values than both high- and low-SR fiber populations for interclick intervals < 4-8 ms. At 85 dB SPL, as interclick interval increased, between 8 and 16 ms, the CAP second-click response converged with that of the high-SR fibers, and by 32 ms, the second-click response values were similar for the CAP, high- and low-SR fibers. 4. The present results are consistent with those of forward masking studies at the level of the auditory nerve in that both demonstrate a short-term reduction of the neural responses. However, the two results differ in that we observed that high-SR fibers exhibited slower recovery than low-SR fibers in response to click-pair stimuli, opposite of the trend observed in the forward masking studies of responses to pure-tone bursts. 5. The present results on auditory nerve fiber responses to click-pair stimuli provide a reference for comparison with responses of central auditory neurons to similar stimuli. This information should serve to elucidate the peripheral contribution to the processing of echoes in the auditory system.

Acoustic Stimulation↗
PubMed1992

Nasal capsule shape changes following septopremaxillary ligament resection in a chimpanzee animal model.

Recent human data suggest a relationship between the disruption of the septopremaxillary ligament (SPL) attachment and lack of anterior midfacial growth in cleft lip and palate (CLP) individuals. Early SPL resection in chimpanzees resulted in premaxillary growth deficits through 1200 days. Since the SPL is also continuous with the nasal bones, the present study was undertaken to investigate compensatory nasal capsule shape changes following SPL resection in a chimpanzee animal model. The study used 17 chimpanzees (Pan troglodytes): seven unoperated controls, five sham surgical controls, and five animals with early (average 144 days) SPL resection. Lateral head x-ray films and dental study models were collected quarterly and landmarks representing boundaries of the nasal capsule were identified. Mean nasal capsule polyhedrons were constructed from linear measurements at 200, 600, and 1000 days. In animals with SPL resection, the nasal capsule appeared truncated, shortened anteroposteriorly, and nasion was displaced posteriorly compared to controls by 600 days. Tensor biometric analysis of the growth/shape changes of the nasal capsule triangles revealed no significant differences across age in SPL resection animals while significant (p less than .05) age-related changes were noted in both control groups. Results showed that early SPL resection resulted in maintaining the neonatal nasal capsule morphology in the chimpanzee and suggested that such early growth mechanisms may be operating in complete CLP individuals as well. These data support the concept of early re-establishment of the SPL in primary nasolabial cleft repair to facilitate midfacial and nasal capsule growth.

Age Factors↗
PubMed1992

Acoustical changes of loudly spoken speech and their effects on speech recognition in hearing-impaired listeners.

The level of speech is usually increased in conversations with unaided hearing-impaired listeners. However, the speaker may talk at conversational levels to aided hearing-impaired persons. In this case, the level of speech is electronically increased by the hearing aid. In the present study, the acoustical changes of loudly spoken speech and their effects on speech recognition were investigated in 20 patients with sensorineural hearing loss. Eight test words of the German Speech Intelligibility Test ('Freiburger Sprachtest') were recorded at original levels of 60 and 75 dB SPL by a male speaker. Both recordings were presented to hearing-impaired subjects at a playback level of 75 dB SPL. Thus, the level of the 60 dB SPL recording was increased electronically by 15 dB. For the 75 dB SPL recording, playback and recording levels were identical. The average whole-word score was 49% for the 60 dB SPL recording and 39% for the 75 dB SPL recording. This difference was statistically significant (0.002 less than P less than 0.005). The results of the speech recognition ability tests could be explained by the acoustical changes of the loudly spoken speech. In the 75 dB SPL recording, the levels of voiceless fricatives, nasals and plosives were significantly lower than in the 60 dB SPL recording. Spectrally, the fundamental frequency was increased and the configuration of the first formant was altered in the 75 dB SPL recording. The significance of the findings for clinical speech audiometry and hearing aid evaluation is discussed.

Acoustic Stimulation↗
PubMed1995

Myelin antigen-coupled splenocytes suppress experimental autoimmune encephalomyelitis in Lewis rats through a partially reversible anergy mechanism.

Mechanisms of adult tolerance induced by injecting myelin Ag/ECDI (ethyl carbodiimide)-coupled splenocytes (Ag-SPL) were evaluated in Lewis rat experimental autoimmune encephalomyelitis (EAE). Rats could be tolerized against the major encephalitogenic epitope of guinea pig basic protein (Gp-BP), residues 72-89, using either S72-89-SPL or crude spinal cord homogenate (SCH)-SPL. In contrast to lymph node responses that were not affected significantly, the proliferation responses of blood T cells were markedly inhibited at the peak of EAE and during the recovery period to both Gp-BP and S72-89, but not to purified protein derivative (PPD), demonstrating Ag-specific tolerance. Tolerance induction reduced the number of infiltrating spinal cord (SC) cells, especially recruited CD45RC+ cells, as well as SC proliferation responses to S72-89 throughout the course of EAE. In contrast, SC response to PPD was increased at onset of EAE, but later during recovery the PPD response was also decreased compared with control rats. Tolerance induced by S72-89-SPL in blood and SC T cells could be reversed by incubation in IL-2, in accordance with an anergy model. BP-specific T cells preincubated in vitro with Gp-BP-SPL were rendered unresponsive to Gp-BP or S72-89, compared with the same T cells preincubated with histone (Hist)-SPL that remained Ag responsive. Consistent with an anergy model, preincubation with BP-SPL+IL-2 partially prevented tolerance induction to BP. T cells tolerized in vitro to BP-SPL induced milder EAE with delayed onset compared with control-tolerized T cells that produced lethal disease. These results demonstrate the efficacy of myelin Ag-coupled SPL in preventing EAE by selective tolerization of encephalitogenic T cells through a partially reversible anergy-induction mechanism.

Amino Acid Sequence↗
PubMed1999

Discrete enhancer elements mediate selective responsiveness of enhancer of split complex genes to common transcriptional activators.

In Drosophila, genes of the Enhancer of split Complex [E(spl)-C] are important components of the Notch (N) cell-cell signaling pathway, which is utilized in imaginal discs to effect a series of cell fate decisions during adult peripheral nervous system development. Seven genes in the complex encode basic helix-loop-helix (bHLH) transcriptional repressors, while 4 others encode members of the Bearded family of small proteins. A striking diversity is observed in the imaginal disc expression patterns of the various E(spl)-C genes, suggestive of a diversity of function, but the mechanistic basis of this variety has not been elucidated. Here we present strong evidence from promoter-reporter transgene experiments that regulation at the transcriptional level is primarily responsible. Certain E(spl)-C genes were known previously to be direct targets of transcriptional activation both by the N-signal-dependent activator Suppressor of Hairless [Su(H)] and by the proneural bHLH proteins achaete and scute. Our extensive sequence analysis of the promoter-proximal upstream regions of 12 transcription units in the E(spl)-C reveals that such dual transcriptional activation is likely to be the rule for at least 10 of the 12 genes. We next show that the very different wing imaginal disc expression patterns of E(spl)m4 and E(spl)mgamma are a property of small (200-300 bp), evolutionarily conserved transcriptional enhancer elements, which can confer these distinct patterns on a heterologous promoter despite their considerable structural similarity [each having three Su(H) and two proneural protein binding sites]. We also demonstrate that the characteristic inactivity of the E(spl)mgamma enhancer in the notum and margin territories of the wing disc can be overcome by elevated activity of the N receptor. We conclude that the distinctive expression patterns of E(spl)-C genes in imaginal tissues depend to a significant degree on the capacity of their transcriptional cis-regulatory apparatus to respond selectively to direct proneural- and Su(H)-mediated activation, often in only a subset of the territories and cells in which these modes of regulation are operative.

Animals↗