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Biomedical subjects

S Prosser

Publications and source records attributed to S Prosser.

At least 19 recordsLinked to original sources
PubMed2006

Noise-induced hearing loss: a study on the pharmacological protection in the Sprague Dawley rat with N-acetyl-cysteine.

Noise-induced hearing loss is one of the most common causes of deafness and, at present, there is no treatment for the recovery of the normal hearing threshold after prolonged exposure to loud acoustic stimuli and the generation of acoustic trauma. Prolonged exposure to noise can cause oxidative stress in the cochlea which results in the loss (via apoptotic pathways) of the outer hair cells of the organ of Corti. It has been demonstrated that some antioxidant molecules, for example L-N-acetyl-cysteine, can prevent oxidative stress in the inner ear. Aim of the study was to evaluate whether L-N-acetyl-cysteine, given at various dosages, can preserve the fine structures of the cochlea from the insult of continuous noise. A series of 18 Sprague Dawley male albino rats were exposed to continuous noise (8 kHz octave band noise, 105 dB SPL, 4 hours), and cochlear functionality was evaluated by recordings of transient evoked otoacoustic emissions and distortion products otoacoustic emissions). The group which showed the best protection was that which received a total dosage of 1500 mg/kg of L-N-acetyl-cysteine. These data suggest that while L-Nacetyl-cysteine can partially protect the cochlea from continuous noise, the protection effect is strongly dose-dependent: lower dosages do not fully protect the cochlea and higher dosages can damage the rat systemically (e.g. pulmonary toxicity).

Acetylcysteine↗
PubMed1998

[Loudness scaling for narrow band noise and speech signal].

A group of normal-hearing subjects underwent an experimental procedure to obtain estimates of loudness for two narrow band noises, centered at 0.25 and 3 kHz respectively, and meaningful unfiltered speech signals (sentences). Stimuli consisted of 12 intensity levels, spaced equally over the dynamic auditory range. The subjects were asked to associate each level of intensity to one 7 loudness categories. The loudness growth for a noise bands is defined by an exponential function. The loudness growth for the speech signal is better approximated by a linear function. However the mean intensity/loudness function shows two steep portions at the low and high intensities and these are separated by a shallow tract between 55 and 75 dB SPL. The loudness growth for meaningful speech signals--differing from the typical exponential function shown by noise stimuli--seems to confirm the contribution of factors that depend on central auditory organization, most likely operated by the perceptive auditory continuity attributes and the semantic content of the speech signals.

Adult↗
PubMed1998

[Measurements of directional hearing aid function].

A digitally programmable hearing aid, equipped with a directional microphone system, has been tested on 5 subjects suffering from severe sensorineural hearing loss. The hearing aids were individually fitted and two gain response curves-respectively designed for omnidirectional (OD) and directional (D) listening-where chosen and tested. The functional gain, as measured from the speech perception threshold for sentences spoken in a quiet environment, was essentially the same for both settings. The D setting revealed its advantages when listening to a frontal speech source while the background noise of a "cocktail party" was delivered from behind the subjects. The D setting permits better tolerance of background noise with a hearing aid, as demonstrated by the signal-to-noise ratio which, at parity performance (50% correct responses), proved 2 to 5 dB lower than that obtained with the OD setting.

Aged↗
PubMed1997

Deletion of 24 amino acids from the C-terminus of phosphatidylinositol transfer protein causes loss of phospholipase C-mediated inositol lipid signalling.

Phosphatidylinositol transfer protein alpha (PITPalpha) is a 32 kDa protein of 270 amino acids that is essential for phospholipase C-mediated phosphatidylinositol bisphosphate hydrolysis. In addition, it binds and transfers phosphatidylinositol and phosphatidylcholine between membrane compartments in vitro. Here we have used limited proteolysis of PITPalpha by subtilisin to identify the structural requirements for function. Digestion by subtilisin results in the generation of a number of slightly smaller peptide fragments, the major fragment being identified as a 29 kDa protein. The fragments were resolved by size-exclusion chromatography and were found to be totally inactive in both in vivo PLC reconstitution assays and in vitro phosphatidylinositol transfer assays. N-terminal sequencing and MS of the major 29 kDa fragment shows that cleavage occurs at the C-terminus of PITP at Met246, leading to a deletion of 24 amino acid residues. We conclude that the C-terminus plays an important role in mediating PLC signalling in vivo and lipid transfer in vitro, supporting the notion that lipid transfer may be a facet of PITP function in vivo.

Amino Acid Sequence↗
PubMed1997

Case-finding incontinence in the over-75s.

BACKGROUND: The under-reporting of incontinence in older persons is well known. However, the general practitioner's (GP's) knowledge of incontinence in this population is less wall documented. AIM: To examine the knowledge of Irish GPs regarding incontinence in patients aged over 75, and to examine the relationship between incontinence and cognitive function in this age group. METHOD: Sixty-four GPs from six faculties of the Irish College of General Practitioners (ICGP), spread geographically over Ireland, administered a questionnaire to 10 of their patients, selected from the General Medical Services list, as part of the ICGP 1993 Care of the Elderly Study. A short test of cognitive function, the AMTS, was administered followed by RCGP (Royal College of General Practitioners) screening questions for incontinence, plus questions with regard to patients' prior reporting of incontinence. GPs were also asked to state their prior knowledge of the incontinence status of the patient and to choose from a list of management options including referral, assigning to a public health nurse, and hospital surgical service. RESULTS: Data were analysed on 527 patients aged over 75 years. Forty-four per cent of persons over 75 years reported having experienced urinary incontinence; 9% reported having experienced faecal incontinence. GPs reported full knowledge of the incontinence status in only 33% of their patients. The effects of low cognitive function, sex, and age on the probability of wetting were analysed using logistic regression modelling. Female sex and low cognitive score increased the likelihood of ever wetting; increasing age increased the likelihood of daily wetting. Poor sensitivities for these models limit their usefulness in clinical practice. CONCLUSION: GPs should have a high index of suspicion for incontinence in persons aged over 75. Thorough history-taking, physical examination, and examinations of therapeutic options for individual cases are recommended.

Age Factors↗
PubMed1997

[Auditory temporal discrimination: effects of stimulus duration, inter-stimulus interval, attention].

A group of 5 normal hearing subjects were studied to determine their perception of the duration of auditory stimuli applied at constant frequency and intensity. In particular, their ability to discriminate between a pair of stimuli was measured. The minimum perceptible difference in duration was evaluated as the Weber fraction (WF) and was a function of the different stimuli duration (from 200 to 3200 ms) and the different interstimulus intervals (from 20 to 7200 ms). In addition, the interference stemming from two different attention conditions was also tested. The WF tended to increase for the 200,400 ms stimuli while it remained unchanged (at around 0.1) for higher durations. On the other hand, the WF was not affected by the inter-stimulus interval although it increased significantly according to attention interference. While these results confirm that estimates of auditory stimuli use attention controlled mechanisms they also suggest that information regarding duration is a stable perception temporarily residing in the short-term auditory memory and that it is not particularly susceptible to temporal decay.

Acoustic Stimulation↗
PubMed1996

ARF and PITP restore GTP gamma S-stimulated protein secretion from cytosol-depleted HL60 cells by promoting PIP2 synthesis.

BACKGROUND: In many cell types, including neutrophils and HL60 cells, there is an absolute requirement for a GTP-dependent step to elicit Ca(2+)-regulated secretion. Neutrophils and HL60 cells secrete lysosomal enzymes from azurophilic granules; this secretion is inhibited by 1% ethanol, indicating that phosphatidate (PA) produced by phospholipase D (PLD) activity may be involved. PLD can use primary alcohols in preference to water during the hydrolytic step, generating the corresponding phosphatidylalcohol instead of PA, its normal product. As ARF (ADP-ribosylation factor) proteins regulate PLD activity and are implicated in constitutive vesicular traffic, we have investigated whether ARF is also required for GTP-dependent secretion in HL60 cells. RESULTS: We have used a cell-permeabilization protocol that allows HL60 cells to become refractory to stimulation with GTP gamma S plus 10 microM Ca2+ with regard to secretion and PLD activity. Permeabilization with streptolysin O for 10 minutes permitted the loss of freely diffusable cytosolic proteins, including ARF proteins. Fractions derived from brain cytosol, enriched in ARF proteins, restored secretory function and PLD activity. The major contaminating protein present in these ARF-enriched fractions was identified as phosphatidylinositol transfer protein (PITP). Unexpectedly, PITP was also found to restore GTP gamma S-dependent secretion. Restoration of secretory function was characterized using recombinant proteins, rARF1 and rPITP alpha and rPITP beta. The rARF1 protein restored both secretory function and PLD activity, whereas PITP only restored secretory function. However, both ARF and PITP were capable of stimulating phosphatidylinositol bis phosphate (PIP2) synthesis. CONCLUSIONS: ARF and PITP restore secretory function in cytosol-depleted cells when stimulated with GTP gamma S plus Ca2+. We have previously shown that PITP participates in the synthesis of PIP2. In comparison, ARF1 activates PLD, producing PA, which is a known activator of phosphatidylinositol-4-phosphate 5 kinase, the enzyme responsible for PIP2 synthesis. We propose that ARF and PITP both restore exocytosis by a common mechanism-promoting PIP2 synthesis.

ADP-Ribosylation Factor 1↗
PubMed1995

Requirement for phosphatidylinositol transfer protein in epidermal growth factor signaling.

Stimulation of phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis is a widespread mechanism for receptor-mediated signaling in eukaryotes. Cytosolic phosphatidylinositol transfer protein (PITP) is necessary for guanosine triphosphate (GTP)-dependent hydrolysis of PIP2 by phospholipase C-beta (PLC-beta), but the role of PITP is unclear. Stimulation of phospholipase C-gamma (PLC-gamma) in A431 human epidermoid carcinoma cells treated with epidermal growth factor (EGF) required PITP. Stimulation of PI-4 kinase in cells treated with EGF also required PITP. Coprecipitation studies revealed an EGF-dependent association of PITP with the EGF receptor, with PI-4 kinase, and with PLC-gamma.

1-Phosphatidylinositol 4-Kinase↗
PubMed1995

Aspects of short-term auditory memory as revealed by a recognition task on multi-tone sequences.

Retention capacity and temporal aspects of auditory short-term memory have been investigated through a multi-tone sequence paradigm and recognition task. There were 37 normally hearing subjects, with (16) and without (21) musical education. They were required to judge whether or not a tonal sequence comprised a tone probe, which was presented following the sequence. The subjects' performance appears to be mainly dependent on the number of the sequence components (n = 2,4,6), while sequence-probe interval (1,3,7 sec) represents a factor of minor weight. In addition, a strong recency effect has been shown for the last sequence component, also extending to the antecedent ones when sequence-probe interval is short. In contrast to studies on verbal short-term memory, no primacy effect has been demonstrated. Musically experienced subjects performed significantly better than naive counterparts. These results have proved to be repeatable in separate groups of subjects, and sensitive to auditory skills associated with musical practice. It is likely that tests of auditory memory based on tonal sequences could be useful in the clinical assessment of subjects with suspected central auditory dysfunction, or subjects who have had a cochlear implant after variable periods of auditory deprivation.

Adolescent↗
PubMed1995

[Auditory memory and multi-tone sequences: effects of proportionality of tone duration].

A group of normally hearing subjects were exposed to tonal pattern in order to ascertain the influence that temporal characteristics of the stimulation may exert on short-term memory of pure tones. Four tones with different frequencies were used as stimuli (500 ms duration, 500 ms off) followed at intervals of 1 and 7 seconds by a probe tone. The subjects' task was to decide whether the sequence included the probe tone or not. The effects of the different duration of the four target tones, which, with regard to the total duration of the tones of the sequence were 12.5%, 25%, 37.5% and 50% respectively, were studied. The decrease in recognition performance relative to to the sequence/probe interval and to the ordinal position of the target, appeared to be governed by the proportionality of the duration of the target-tones. The ordinal position of the targets proved to be the factor which most influenced recognition performance. On the basis of these data, it may be hypothesized that a mechanism of attention, activated by the temporal characteristics of the tones in the sequence, improves the ability to store, recall and recognize target elements in multi-tone sequences.

Acoustic Stimulation↗
PubMed1992

Short report: omeprazole plus antibiotic combinations for the eradication of metronidazole-resistant Helicobacter pylori.

Twenty-eight Helicobacter pylori-positive patients with metronidazole-resistant isolates and 25 with metronidazole-sensitive isolates were treated for 14 days with 40 mg omeprazole nocte plus 500 mg amoxycillin t.d.s. Eradication of H. pylori, defined as absence of the organism one month after cessation of treatment, was assessed using the [14C]urea breath test. The eradication rate in patients with metronidazole-resistant isolates was 14/28 (50%) while that in patients was metronidazole-sensitive isolates was 12/25 (48%). In contrast to these encouraging eradication rates, very poor results were obtained with a 7-day course of omeprazole (40 mg nocte) in combination with erythromycin ethylsuccinate (500 mg q.d.s.) and tripotassium dicitrato bismuthate tablets (120 mg q.d.s.). The latter eradication rates were 3/20 (15%) in patients taking erythromycin tablets and 3/19 (16%) in those taking a liquid formulation of erythromycin. All treatment regimens were well tolerated and all patients completed the prescribed course of therapy.

Adult↗
PubMed1992

Cochlear and neural dysfunction in acoustic neuroma: can they be separately revealed by auditory brain-stem wave V latency?

Cochlear and retrocochlear lesions may be differentiated by a diagnostic index (D5), which is derived from the patient's auditory brain-stem wave V latency and pure-tone hearing threshold at 2 to 4 kHz. The D5 values obtained from 49 cases of acoustic neuroma (AN) have been shown to share some properties with D5 values of patients with cochlear hearing loss (280 cases), indicating a lesser prolongation of wave V latency in cases with pronounced hearing loss. Assuming this finding is indicative of some degree of cochlear impairment concomitant to the neural dysfunction, AN data were corrected in an attempt to remove the effects of cochlear impairment. The resulting D5 values could reflect the delay in wave V solely due to the neural dysfunction. A significant relationship between these D5 values and tumour size seems to support this hypothesis.

Adult↗
PubMed1992

Observations on the ABR I-V interval in a clinical sample of elderly patients.

ABR I-V interval in elderly patients, analysed by multiple regression analysis, was found to be dependent on hearing threshold slope and sex, while the contribution of age and hearing loss was not significant. Since these results partly disagree with other reports which demonstrate that I-V interval is significantly related to age and hearing threshold, caution is suggested in inferring general conclusions on age effects, if data are drawn from clinical samples.

Aged↗
PubMed1991

[Relations and variability of the stapedial reflex threshold and psychoacoustic discomfort threshold].

Ten normal hearing subjects were subjected to repeated measurement of the stapedial reflex threshold (RT) and loudness discomfort threshold (DT) during five separate sessions. On the average DT was 4.8 dB higher than the RT. The sessions did not affect the intra-individual variance of either threshold. A regression analysis demonstrated that a significant linear relationship exists between RT and DT. However, DT may be lower than RT when the latter is shifted towards its upper variance boundary. Hence, RT and DT are not equivalent as indicators of the upper limit of loudness tolerance; since DT revealed a low intra-subject variance, such a psychoacoustic measurement may be reliably used for clinical purposes.

Acoustic Impedance Tests↗