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Biomedical subjects

J C Cooper

Publications and source records attributed to J C Cooper.

At least 37 records · Page 2Linked 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↗
PubMed1995

Localization of vascular endothelial growth factor and its receptor, flt, in human placenta and decidua by immunohistochemistry.

Vascular endothelial growth factor is a secreted angiogenic growth factor the mRNA of which is present in the placenta. The mRNA encoding the vascular endothelial growth factor receptor, flt, has also been demonstrated in placenta, with trophoblast appearing to be a novel site of flt expression. We investigated the expression of both vascular endothelial growth factor and flt-like immunoreactivity in first trimester and term placentae. In the first trimester, vascular endothelial growth factor immunoreactivity was localized to placental macrophages (Hofbauer cells), and in decidua, to glandular epithelium and maternal macrophages. In the term placenta, vascular endothelial growth factor immunoreactivity was present in extravillous trophoblast and in extracellular material. Flt immunoreactivity was demonstrated on extravillous trophoblast in first trimester and term, and on Hofbauer cells within placental villi. This complex pattern of both vascular endothelial growth factor and flt-like immunoreactivity suggests that vascular endothelial growth factor may be involved not only in the regulation of placental angiogenesis, but also in trophoblast invasion.

Decidua↗
PubMed1995

Growth factors in pregnancy.

The role of growth factors in pregnancy is a rapidly expanding subject. With the advent of molecular biological techniques more and more detailed information is available to the researcher. This review does not attempt to be exhaustive in its coverage of growth factors in pregnancy, rather it tries to give a brief taste of the possible roles that they may play in pregnancy by considering three specific factors, leukaemia inhibitory factor, colony stimulating factor-1 and vascular endothelial growth factor.

Animals↗
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↗
PubMed1992

Variance analysis refines overhead cost control.

Many healthcare organizations may not fully realize the benefits of standard cost accounting techniques because they fail to routinely report volume variances in their internal reports. If overhead allocation is routinely reported on internal reports, managers can determine whether billing remains current or lost charges occur. Healthcare organizations' use of standard costing techniques can lead to more realistic performance measurements and information system improvements that alert management to losses from unrecovered overhead in time for corrective action.

Accounting↗
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↗