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Biomedical subjects

C Rogers

Publications and source records attributed to C Rogers.

At least 127 records · Page 7Linked to original sources

Isolation and characterization of histogranin, a natural peptide with NMDA receptor antagonist activity.

Histogranin, was co-purified with bombesin-like immunoreactive peptides from bovine adrenal medulla. Its structure, H-Met-Asn-Tyr-Ala-Leu-Lys-Gly-Gln-Gly-Arg-Thr-Leu-Tyr-Gly-Phe-COOH, was determined by gas-phase Edman degradation. It was in accordance with its amino acid composition and corresponded to a 15 amino acid fragment (fragment 86-100) of histone H4 with substitutions in positions 1 (Val), 2 (Val) and 7 (Arg). The peptide was synthesized by the solid-phase procedure and the synthetic product was identical to the natural peptide as determined by its retention time on three analytical high-performance liquid chromatography systems. An antibody was raised against synthetic [Ser1]histogranin and used to monitor the presence of histogranin in various rat tissues and subcellular fractions of bovine adrenal medulla. In rats, immunoreactive histogranin was mainly concentrated in the pituitary (5065 pmol/g) and the adrenal glands (268 pmol/g), but it was also present in other tissues including the brain (1.6 pmol/g) and blood plasma (24 fmol/ml). A neuropeptide function for the adrenal peptide was suggested by its relative high concentration in chromaffin granules (42 fmol/mg protein as compared with 1 fmol/mg protein in cytosol) and its release from perfused bovine adrenal glands. In rat brain membrane preparations, synthetic histogranin displaced the binding of [3H]CGP 39653, a specific ligand of N-methyl-D-aspartate (NMDA) receptor. The displacement curve was biphasic with IC50 of 0.6 and 3955 nM, representing 33% and 67% of the binding sites, respectively. Intracerebroventricular (i.c.v.) injection of the peptide (5-100 nmol) in mice produced a dose-dependent protection against NMDA (0.5-1.0 nmol) -induced convulsions but not against (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA, 0.25-2.0 nmol), kainate (0.25-0.75 nmol) and bicuculline (1-10 nmol)-induced convulsions. These results suggest that histogranin may be an endogenous modulator of NMDA receptor functions.

2-Amino-5-phosphonovalerate↗

Continuous intercostal nerve block versus epidural morphine for postthoracotomy analgesia.

Twenty patients undergoing elective thoracotomy were randomized into two groups, receiving either lumbar epidural morphine (n = 10) or continuous extrapleural intercostal nerve block (n = 10). Subjective pain relief was assessed on a linear visual analogue scale. Pulmonary function (peak expiratory flow rate, forced expiratory volume in 1 second, and forced vital capacity) was measured on the day before operation and daily for 4 days after operation. Pulse oximetry monitoring was used to determine the incidence of hypoxemia. No significant difference was observed between the groups concerning pain relief (except at 28 hours, in favor of the intercostal nerve block group), respiratory performance, or arterial oxygen saturation. Vomiting, pruritus, and urinary retention occurred only in the epidural group, whereas nausea occurred significantly less frequently in the extrapleural group. We conclude that after thoracotomy continuous extrapleural intercostal nerve block is as effective as lumbar epidural morphine in reducing postoperative pain and restoring pulmonary mechanics. Because of the significantly lower complication rates we favor continuous extrapleural intercostal nerve block for postthoracotomy analgesia.

Adult↗

Identification of specific pathways of communication between the CNS and NK cell system.

The specific signals and pathways utilized by the natural killer (NK) cell system and the central nervous system (CNS) that results in the conditioned response (CR) is not clearly understood. Single trial conditioning of the NK cell activity provides us with a model to probe the mechanisms of communication between two major systems (Immune and CNS) which are involved in the health and disease of the individual. The studies show that the IFN-beta molecules possess the properties attributed to the unconditioned stimulus (US). IFN-beta can penetrate the CNS and evoke the elevation of NK cell activity in the spleen. This unconditioned response (UR) can be linked to a specific conditioned stimulus (CS). Specific odors such as camphor provide a neural pathway for the CS to associate with the US. Evidence is presented that in conditioning there are two locations where memory develops. The CS/US association is made centrally and its memory is stored at a central location, but the memory for the specificity of the odor is presumably stored in the olfactory bulbs. The CS recalls the CR by triggering the olfactory neural pathway which, in turn, signals the hypothalamic-pituitary axis to release mediators that modulate the activity of NK cells in the spleen. These results imply that through conditioning one has direct input into the regulatory hypothalamus that controls the internal environment of the organism and the health and disease of the individual. Consequently, it is not inconceivable that through this approach we might be able to alter the course of a disease process.

Animals↗

Influences upon attendance at out-patient facilities--the contribution of linear-logistic modelling.

The research on attendance at out-patient psychiatric facilities has produced conflicting evidence that provides little guidance for the practitioner. It is suggested that inadequate data exploration could explain some of the discrepant findings. Analyses of multi-way tables using linear-logistic models were undertaken to demonstrate patterns of association that cannot be revealed through the use of simple chi-square tests on two-way contingency tables. The variables chosen for these analyses were those that have produced conflicting findings in the literature on children's attendance at child guidance facilities.

Adolescent↗

Phototherapeutic keratectomy for Reis Bucklers' corneal dystrophy.

Superficial keratectomy, penetrating and lamellar keratoplasty have all been advocated when intervention in Reis Bucklers' corneal dystrophy is necessary because of diminished visual acuity. In this study, 11 eyes were treated by phototherapeutic keratectomy with an excimer laser. Two eyes had previously been treated by penetrating keratoplasty. The visual acuity improved in all eyes, from an average of 6/60 to 6/9 with complete cessation of recurrent erosions. The technique was modified, with experience, to minimise the hyperopic shift that occurs with this procedure. Phototherapeutic keratectomy has significant advantages over other procedures and is now the procedure of choice once surgery is required in Reis Bucklers' dystrophy.

Adolescent↗

Inhibition of experimental neointimal hyperplasia and thrombosis depends on the type of vascular injury and the site of drug administration.

BACKGROUND: Heparin inhibits vascular smooth muscle cell proliferation in tissue culture and limits neointimal hyperplasia after experimental arterial injury but has been ineffective in reducing clinical restenosis. We examined how this discrepancy might reflect suboptimal drug-tissue interactions and/or differences in the vascular response to injury. METHODS AND RESULTS: Intravenous infusion was compared with local administration of heparin to injured rabbit iliac arteries either from drug-impregnated polymeric controlled release matrices in the perivascular space or from drug-releasing endovascular stents. Occlusive thrombosis, seen in 42% of control stent-bearing arteries, and partial thrombosis were virtually eliminated by heparin delivery from any route. Intimal area 14 days after balloon withdrawal denudation alone was reduced to an equal extent by continuous systemic heparin or by perivascular heparin for the first 3 days. In contrast, endovascular stents produced more exuberant neointimal hyperplasia, the inhibition of which required continuous rather than only early heparin administration. Neither perivascular delivery limited to the first 3 days nor stent-based delivery reduced neointimal hyperplasia as effectively. CONCLUSIONS: The antiproliferative and antithrombotic effects of heparin differ markedly, depending on the type of arterial injury and the mode of drug administration. Different forms of injury may require different therapies, and complications of arterial intervention such as excessive neointimal hyperplasia and thrombosis may demand alternate therapeutic regimens. Duration, dose, and site of delivery rather than frank resistance to therapy may explain why experimentally effective antiproliferative and antithrombotic agents fail clinically.

Administration, Topical↗

Characterization of [125I][Ser1]histogranin binding sites in rat brain.

The binding characteristics of histogranin (HN), an endogenous peptide first recognized for its antagonism of N-methyl-D-aspartate (NMDA) responses, were determined in membrane preparations of rat brain. [125I][Ser1]HN, a stable bioactive analog of HN, bound specifically and reversibly to a homogenous population of high-affinity sites with a Kd of 25 nM and a Bmax of 410 fmol/mg protein. The binding of [125I][Ser1]HN increased linearly with membrane protein concentration and was destroyed upon membrane pretreatment with trypsin. The binding displayed rapid association and dissociation kinetics and was blocked by peptides possessing close homology with HN in the following order: [Ser1]HN-(1-15) > HN > [Ser1]HN-(1-14) > HN-(2-15) > [Ser1]-HN-(1-10) > HN-(6-10). Unrelated peptides such as substance P, beta-endorphin, neuropeptide Y, [Met5]enkephalin, [Leu5]enkephalin, dynorphin A(1-13) and neuromedin C were inactive in competition binding assays against [125I]Ser1]HN. Ligands of the binding domains of the NMDA receptor, such as (+)3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, (+) 5-methyl-10,11-dihydro 5H-dibenzo[a, d]cyclohepten-5,10-imine hydrogen maleate, 1-N-(2-thienyl)cyclohexylpiperidine, glycine and glutamate were also ineffective in competing for [125I][Ser1]HN binding sites. Interestingly, specific ligands for the polyamine site on the NMDA receptor, as well as the cations Mg++ and Zn++ inhibited [125I][Ser1]HN binding. The polyamine antagonist diethylenetriamine produced a noncompetitive inhibition with an IC50 (175 nM) comparable to that of HN (75 nM). The cations Zn++ and Mg++ displaced [125I][Ser1]HN binding with IC50 values of 18 and 240 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Gang-related homicides in Los Angeles County.

The incidence of gang homicides in Los Angeles County has increased faster than that of non-gang homicides in the past decade. This study compares characteristics of gang homicide victims with those of non-gang homicide victims for the year 1987. In 1186 cases, gang members were more likely to be young Black men who died of gunshot wounds. Gang homicide victims were more likely to die of firearm injuries in the early evening, and were more likely to die in a relatively small area of Los Angeles County. Drive-by shooting was highly associated with gang homicide.

Adolescent↗

Indomethacin and sodium carbonate effects on conditioned fever and NK cell activity.

The augmentation of natural killer (NK) cell activity and elevation of body temperature (fever) can both be conditioned using camphor odor as the conditioned stimulus (CS) and poly I:C as the unconditioned stimulus (US). While both responses can be conditioned in parallel fashion as shown previously, our results indicate the conditioned learning of these responses may not follow along a common path. We found that injection of a 1% solution of sodium carbonate was able to consistently block the CS/US learning of the NK cell response but did not block conditioning of the fever response. In contrary fashion, mice treated with indomethacin (which inhibits prostaglandin-induced fever) dissolved in the sodium carbonate solution did not learn in consistent fashion the fever response. However, indomethacin-treated animals were able to recall the NK cell response. These results support the view that although the same mediator, IFN-beta, is responsible for the conditioned learning of the NK cell and fever responses both the learning and recall of the responses are initiated along separate pathways.

Animals↗

Characterization of [3H]desmethylimipramine binding in bovine adrenal medulla: interactions with sigma- and (or) phencyclidine-receptor ligands.

High-affinity binding sites (apparent KD 2.87 nM) for [3H]desmethylimipramine ([3H]DMI), have been demonstrated and characterized in membrane preparations of bovine adrenal medulla. The binding of [3H]DMI improved upon pretreatment of the membrane with KCl and was saturable, sodium dependent, and potently inhibited by nisoxetine and imipramine. [3H]DMI binding was also inhibited by various phencyclidine (PCP)- and (or) sigma-receptor ligands, with the following order of potency: haloperidol > rimcazole > (-)-butaclamol > dextromethorphan > MK-801 > (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP) > PCP > N-(2-thienyl)cyclohexyl-3,4-piperidine (TCP) > (+)-SKF-10047 > (-)-SKF-10047. The inhibition produced by sigma ligands was not attributed to stimulation of either sigma 1- or sigma 2-receptors, owing to inactivity of the selective sigma-receptor ligands (+)-pentazocine and 1,3-di(2-tolyl)guanidine (DTG). The inhibition of [3H]DMI binding by sigma- and PCP-receptor ligands was not attributed to PCP1- or PCP2-receptor stimulation, owing to the decreased potency (100-fold) of these ligands in [3H]DMI assays compared with the affinity for brain PCP1 sites, and the ineffectiveness of the PCP2-ligand N-(1-(2-benzo(b)thiophenyl)cyclohexyl)piperidine (BTCP). Scatchard analysis of the inhibition by the sigma-ligands haloperidol and (+)-3-PPP, as well as the PCP1 receptor ligand MK-801, demonstrated noncompetitive interaction with the site bound by [3H]DMI. These studies indicate that bovine adrenomedullary membranes possess a specific receptor for the noradrenaline uptake inhibitor [3H]DMI, which is sensitive to allosteric modulation produced by PCP and sigma-ligands.

Adrenal Medulla↗

Insulin, glibenclamide or metformin treatment for non insulin dependent diabetes: heterogenous responses of standard measures of insulin action and insulin secretion before and after differing hypoglycaemic therapy.

Using carefully selected relatively non-obese non insulin dependent diabetic patients, we were not able to show differences in standard measures of insulin production or insulin action between patients treated with a long acting crystalline zinc insulin, with glibenclamide, or with metformin for a six week period. All three drugs were hypoglycaemic, but a fall in basal hepatic glucose output measured by the 3H3 glucose technique was only seen in those patients who had an initial fasting plasma glucose above 12.0 mmol/l, irrespective of treatment.

Blood Glucose↗

Phenotyping and genotyping of composite lymphoma with Ki-1 component.

A case of composite lymphoma consisting of an anaplastic large-cell Ki-1 lymphoma and a small-cell follicular lymphoma was found in the splenic hilar lymph node of a 66-year-old woman. The Ki-1 lymphoma showed monoclonal IgM-lambda and CD 20, CD 74, and CDw 75 antigens by immunostaining and CD 19, CD 20, CD 22, and lambda antigens by flow cytometry. The follicular lymphoma also showed monoclonal IgM-lambda, and CD 20 and CDw 75 antigens but not CD 74 and CD 30 (Ki-1) by immunostaining. Flow cytometric analysis of the follicular lymphoma component was not conclusive, as it was impossible to separate the neoplastic from the normal small B lymphocytes. Ki-1 lymphoma usually is seen in childhood and is mostly of T cell origin. It is, therefore, unusual to find Ki-1 antigen component in a composite lymphoma of B-cell origin in an adult. However, there has been evidence to suggest that B-cell Ki-1 lymphoma may be related to follicular lymphoma. Thus, our case may represent a follicular lymphoma transforming into a Ki-1 lymphoma. Immunogenotyping in this case revealed that the two components were probably of the same clonal origin, as they seemed to share the same light chain gene. The presence of rearrangement in the switch region of the IgH in our case without the actual occurrence of heavy chain switching may have triggered somatic recombination in the IgH complex. This series of events may have led to the transformation of a low-grade lymphoma into a high-grade lymphoma, accounting for the two morphologic patterns seen in our bimorphic lymphoma.

Aged↗

Ultrasonography in the acute abdomen.

In a prospective study 152 consecutive patients presenting with acute abdominal pain were assessed clinically and an ultrasonographic examination was performed immediately. Of these, 16 (11 per cent) patients would normally have had an immediate ultrasonographic scan requested; routine (within 24 h of admission) ultrasonographic examination would have been requested in a further 66 (43 per cent) patients. In 70 (46 per cent) patients an ultrasonographic examination would not have been requested. Ultrasonography altered the diagnosis in one patient from probable appendicitis to cholecystitis. Ultrasonography missed one abdominal aortic aneurysm and one empyema of the gallbladder. Ultrasonography had a sensitivity of 96 per cent, a specificity of 94 per cent, a positive predictive value of 96 per cent, a negative predictive value of 94 per cent and an accuracy of 95 per cent in diagnosing appendicitis. Exactly the same values were found for the clinical diagnosis of appendicitis. The study shows that routine immediate ultrasonographic examination of the acute abdomen is rarely helpful, with the possible exception of appendicitis. Where an urgent ultrasonographic scan is necessary on clinical grounds the expertise of a radiologist is probably required, whereas in specific areas, for example in the diagnosis of right iliac fossa pain, there may be a place for training the surgical trainee.

Abdomen, Acute↗