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Biomedical subjects

J C Cooper

Publications and source records attributed to J C Cooper.

At least 19 recordsLinked to original sources
PubMed1995

Physostigmine, galanthamine and codeine act as 'noncompetitive nicotinic receptor agonists' on clonal rat pheochromocytoma cells.

The acetylcholine esterase inhibitor (-)-physostigmine has been shown to act as agonist on nicotinic acetylcholine receptors from muscle and brain, by binding to sites on the alpha-polypeptide that are distinct from those for the natural transmitter acetylcholine (Schröder et al., 1994). In the present report we show that (-)-physostigmine, galanthamine, and the morphine derivative codeine activate single-channel currents in outside-out patches excised from clonal rat pheochromocytoma (PC12) cells. Although several lines of evidence demonstrate that the three alkaloids act on the same channels as acetylcholine, the competitive nicotinic antagonist methyllycaconitine only inhibited channel activation by acetylcholine but not by (-)-physostigmine, galanthamine or codeine. In contrast, the monoclonal antibody FK1, which competitively inhibits (-)-physostigmine binding to nicotinic acetylcholine receptors, did not affect channel activation by acetylcholine but inhibited activation by (-)-physostigmine, galanthamine and codeine. The three alkaloids therefore act via binding sites distinct from those for acetylcholine, in a 'noncompetitive' fashion. The potency of (-)-physostigmine and related compounds to act as a noncompetitive agonist is unrelated to the level of acetylcholine esterase inhibition induced by these drugs. (-)-Physostigmine, galanthamine and codeine do not evoke sizable whole-cell currents, which is due to the combined effects of low open-channel probability, slow onset and slow inactivation of response. In contrast, they sensitize PC12 cell nicotinic receptors in their submaximal response to acetylcholine. While the abundance of nicotinic acetylcholine receptor isoforms expressed in PC12 cells excludes identification of specific nicotinic acetylcholine receptor subtypes that interact with noncompetitive agonists, the identical patterns of single-channel current amplitudes observed with acetylcholine and with noncompetitive agonists suggested that all PC12 cell nicotinic acetylcholine receptor subtypes that respond to acetylcholine also respond to noncompetitive agonist. The action of noncompetitive agonists therefore seems to be highly conserved between nicotinic acetylcholine receptor subtypes, in agreement with the high level of structural conservation in the sequence region harboring major elements of this site.

Acetylcholine↗
PubMed1994

Structural studies on porphobilinogen deaminase.

The X-ray crystallographic analysis of porphobilinogen deaminase (hydroxymethylbilane synthase, EC 4.3.1.8) shows the polypeptide chain folded into three domains, (1) N-terminal, (2) central and (3) C-terminal, of approximately equal size. Domains 1 and 2 have a similar overall topology, a modified doubly wound parallel beta-sheet. Domain 3 is an open-faced three-stranded antiparallel beta-sheet, with one face covered by three alpha-helices. The active site is located between domains 1 and 2. The dipyrromethane cofactor linked to cysteine 242 protrudes from domain 3 into the mouth of the cleft. Flexible segments between domains 1 and 2 are thought to have a role in a hinge mechanism, facilitating conformational changes. The cleft is lined with positively charged, highly conserved, arginine residues which form ion pairs with the acidic side chains of the cofactor. Aspartic acid 84 has been identified as a critical catalytic residue both by its proximity to the cofactor pyrrole ring nitrogen and by structural and kinetic studies of the Asp-84-->Glu mutant protein. The active site arginine residues have been altered by site-directed mutagenesis to histidine residues. The mutant proteins have been studied crystallographically in order to reconcile the functional changes in the polymerization reaction with structural changes in the enzyme.

Crystallography, X-Ray↗
PubMed1994

Health and Nutrition Examination Survey of 1971-75: Part I. Ear and race effects in hearing.

The Health and Nutrition Examination Survey of 1971-75 contains unique hearing data because its design permits generalization to noninstitutionalized civilians in the continental United States. Air-conduction thresholds and their relationships to age, ear, gender, frequency, and race were examined in unscreened 25- to 74-year-olds. Although the observed effects of age, gender, and frequency were expected, three aspects of the results were remarkable. First, there was support for previous observations that older females have poorer low-frequency hearing. Second, there was an ear effect among white males who had poorer 2 and 4 kHz mean thresholds on the left at all ages. Third, there was a pattern of poorer mean thresholds for blacks that was particularly evident in comparisons between black and white females.

Adult↗
PubMed1994

Health and Nutrition Examination Survey of 1971-75: Part II. Tinnitus, subjective hearing loss, and well-being.

The Health and Nutrition Examination Survey of 1971-75 contains valuable information because it provides unbiased estimates of the state of hearing in the general population. Here, three facets of the subjective aspects of hearing loss are examined: frequent and bothersome tinnitus, ratings of hearing, and general well-being. The period prevalence of frequent, bothersome tinnitus varied with race and gender (13 to 17%) with higher rates among blacks and females. The mean air-conduction thresholds (0.5 to 4 kHz) of those reporting frequent and bothersome tinnitus did not exceed 32 dB HL. Mean audiograms associated with those who rated both ears good, fair, poor, or deaf were significantly different from each other. Mean poorer ear audiograms for those rating one ear as good were significantly better than those for comparable symmetrical ratings. Last, there was no clear, consistent relationship between audiometric thresholds and measures of well-being.

Acoustic Stimulation↗
PubMed1992

Otologic complaints in temporomandibular joint syndrome.

Complaints of diminished hearing or reduced speech discrimination frequently accompany temporomandibular dysfunction. There is no consensus as to the mechanism of their occurrence or the alteration of these symptoms with the treatment. We studied 12 subjects with internal derangement of the temporomandibular joint (treated surgically) and nine subjects with myofascial pain disorder (treated medically), and we found no difference between the groups in pretreatment audiometric findings or in their degree of otologic symptoms. Similarly, there were no differences in posttreatment audiometric measures and there were no significant treatment effects. Furthermore, there was no correlation between subjects' complaints of reduced hearing sensitivity or discrimination and audiometric results. The apparently significant reduction in symptoms experienced by some subjects in the absence of audiometric change suggests the operation of unmeasured factors in their response to treatment.

Adolescent↗
PubMed1992

Central auditory processing disorders in the elderly: the effects of pure tone average and maximum word recognition.

We previously examined central auditory processing disorders and the effect of age in 1026 64- to 93-yr-olds. Here, we correlated three indices of central auditory processing disorders with age, pure tone averages (PTA) and maximum word recognition scores. With one exception, correlations of indices with PTA equaled or exceeded those with age. With one exception, correlations with word recognition scores were insignificant or smaller than those with age. Although statistically significant, the magnitudes of most effects were small (0.003 less than r2 less than 0.146). However, PTA accounted for approximately 30% of the variability in corrected Staggered Spondaic Word test error scores.

Age Factors↗
PubMed1991

The role of percutaneous transluminal angioplasty in the treatment of critical ischaemia.

In an attempt to establish the overall role played by percutaneous transluminal angioplasty in the treatment of critical ischaemia we studied 101 consecutive patients (110 limbs) who presented to one vascular unit over an 18 month period with this diagnosis. All patients underwent assessment with Doppler waveform analysis and arteriography and decisions about further management were made jointly by the surgical team and vascular radiologist. Results showed that only 24/110 limbs (22%) had lesions that were suitable for treatment with angioplasty alone. In addition one patient underwent angioplasty in conjunction with a distal bypass. Forty-one of the 110 limbs (37%) underwent reconstructive surgery, 18/110 (16%) primary amputation and 26/110 (24%) conservative treatment. Of those 24 limbs undergoing angioplasty, four were technically unsuccessful, and six were technically successful but without clinical improvement and all required alternative treatment. Only 12/110 limbs (11%) showed clinical improvement during their admission following angioplasty. We conclude that although angioplasty can be used successfully to treat critical ischaemia the overall numbers of patients who are suitable for treatment and who gain benefit from it is small.

Adult↗
PubMed1991

Hearing in the elderly--the Framingham cohort, 1983-1985: Part II. Prevalence of central auditory processing disorders.

The relation between central auditory processing disorders (CAPD) and age has been described in selected subjects. However, the prevalence of CAPD in the general population has not been established. We tested 1026, 64- to 93-yr-old members of the Framingham Heart Study cohort with Central Institute for the Deaf W-22 lists (CID W-22) in quiet, the Synthetic Sentence Identification test with ipsilateral competing message (SSI-ICM), and the Staggered Spondaic Word test. The presence or absence of CAPD could be established with at least one of three indices in 1018 subjects. The CID W-22 performance-intensity function rollover index was greater than 0.20 in 1.4% of 1009 subjects. The difference between maximum CID W-22 and SSI-ICM (0 dB message-to-competition ratio) scores was greater than 20% in 18.2% of 816 subjects. The Staggered Spondaic Word category was moderately, severely, over-corrected moderately, or over-corrected severely abnormal in 10.7% of 941 subjects (using 12-59-yr-olds' norms and adjusting scores when appropriate). Abnormal results on any one index occurred in 22.6% of the subjects. Thus, we conclude that the prevalence of CAPD in the elderly is less common than previous studies would suggest. Furthermore, although the rate of CAPD increased with age, age accounted for no more than 15% of the variability of any of the three indices. Therefore, its presence is dominated by factors other than chronological age.

Age Factors↗
PubMed1991

Incidence of hearing decline in the elderly.

Pure-tone audiometry was done on 1475 persons on two occasions 6 years apart by the same audiologist in the same facility. The age of the subjects ranged from 58 to 88 years at the initial testing and 63 to 95 at the second. The average 6-year threshold change ranged from 1 to 8 dB at 250-6 kHz and 10-15 dB at 8 kHz. The differences in thresholds fell into two patterns, one for low frequencies (250-1 kHz) and the other for high frequencies (4-8 kHz). For the lows, thresholds worsened at an increasing rate with increasing age independent of the initial hearing level, and women's thresholds worsened more than men's. For the highs, the rate of threshold change decreased with age and with the initial threshold at rates that did not differ between genders. Using a change in PTA (0.5, 1, 2 kHz) of greater than 10 dB as a criterion, significant worsening occurred in the right ear in 8.5%, in the left ear in 13.5%, and in both ears of 4.1% of the subjects over the 6 year period. The rate of significant worsening increased with age. Although hearing loss increased with age, age alone accounted for less than 10% of the variance. Therefore, factors that co-vary with age may be responsible. The difference in phenomena between the low frequencies and the highs suggests that two different processes are occurring. Hair-cell degeneration is the most likely cause for the change in the high frequencies. Strial atrophy or other intracochlear processes may be the cause of the low frequency changes.

Age Factors↗
PubMed1991

The use of computed tomography in the evaluation of large multinodular goitres.

This study reports one unit's experience of the value of computed tomography (CT) in the evaluation of 24 patients with large cervical and retrosternal goitres. Of these patients, 17 were thought clinically to have symptoms of tracheal compression, but the CT demonstrated significant narrowing in only 12 cases. In the other five patients, surgery was deferred and other causes for their symptoms sought and treated. Seven patients were asymptomatic and CT failed to reveal any evidence of tracheal compression in six. In the remaining patient, however, CT revealed gross narrowing and urgent surgery was performed. When compared with CT, chest/thoracic inlet radiographs were misleading in 48% of patients, with tracheal narrowing being overestimated and underestimated. We conclude that CT gives useful information about tracheal compression in patients with large multinodular goitres, and is more accurate than chest/thoracic inlet radiographs.

Adult↗
PubMed1990

Hearing in the elderly: the Framingham cohort, 1983-1985. Part I. Basic audiometric test results.

Many studies have documented the decline in auditory function with age. We broaden that data base in this the first of a series of reports emanating from the auditory testing of the Framingham cohort during biennial exam 18. The results of the auditory questionnaire, hearing sensitivity, acoustic compliance measures, and word recognition tests obtained from 1662 men and women in their 60th through 90th decades are presented. Pure-tone thresholds increased with age but the rate of change with age did not differ by gender even though men had poorer threshold sensitivity. Maximum word recognition ability declined with age more rapidly in men than in women and was poorer in men than in women at all ages. Acoustic compliance and middle ear pressure did not vary with gender or age. Acoustic reflex thresholds to a contralateral stimulus at 1 kHz increased slightly with age, more in women than in men; ipsilateral acoustic reflex thresholds did not vary with age or gender. Hearing aids were being used in only 10% of subjects likely to benefit from amplification.

Acoustic Impedance Tests↗