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Biomedical subjects

J Gilbert

Publications and source records attributed to J Gilbert.

At least 199 records · Page 11Linked to original sources

Correspondence analysis applied to steroid receptor binding.

The relative binding affinities of 48 steroids for four classes of hormone receptor (progestin, PR; androgen, AR; glucocorticoid, GR; mineralocorticoid, MR) have been analyzed by correspondence analysis. The steroids were, for the most part, derivatives of nortestosterone, differing by their degree of unsaturation, by the presence or absence of a 17 alpha-ethynyl group, and by the length of the C-13 alkyl substituent. Derivatives of norprogesterone were included as reference compounds. Distribution maps visualizing the results of the mathematical analysis revealed that the majority of the test steroids were within the zone of influence of AR and PR and had limited affinity for GR and MR. Overall lack of specificity and enhanced affinity for GR and MR were induced by increasing unsaturation and by the presence of a C-13 ethyl group. The general and specific conclusions of the analysis confirm and extend previous intuitive and partial interpretations of the data. Correspondence analysis, however, has the advantage of taking into account the sum total of the available information, without any preconceived notion of the relative importance of a specific structural feature or biological parameter and, furthermore, enables simultaneous representation on a single graph of the receptor and steroid fields. The present example demonstrates the use of this type of methodology in processing routine screening data involving multiple parameters.

Chemical Phenomena↗

Sudden cardiac death in a southeast Asian immigrant: clinical, electrophysiologic, and biopsy characteristics.

The syndrome of sudden cardiac death in southeast Asians has only recently been given attention in the American medical literature. This case report describes a patient who presented with this rare syndrome. The physical examination, Holter monitor, 2-D echocardiogram, exercise treadmill test, radionuclide ventriculogram, coronary angiography, and endomyocardial biopsy were all normal. Programmed ventricular stimulation reproducibly induced sustained polymorphic ventricular tachycardia. Oral procainamide, oral quinidine and oral quinidine plus propranolol were not successful in suppressing inducible polymorphic ventricular tachycardia. The arrhythmia remained inducible after six weeks of oral amiodarone therapy. However, he has no clinical recurrences while on amiodarone after one year of follow-up.

Adult↗

Gastrografin in acute meconium ileus equivalent.

Twenty-five (37%) patients with cystic fibrosis attending our clinic have experienced acute meconium ileus equivalent. In one year 37 of 40 episodes were treated with single dose oral Gastrografin with an 81% success rate, 75% being treated as outpatients. Patients found this treatment preferable to other recommended treatment.

Acute Disease↗

Patterns of reaction of monoclonal antibodies HMFG-1 and -2 with benign breast tissues and breast carcinomas.

The monoclonal antibodies HMFG-1 and HMFG-2 are directed against different epitopes on a large molecule in the human milk fat globule and are also expressed on breast tumors. Here we examine the relative intensity of staining of the two antibodies in formalin fixed paraffin embedded tissue sections from malignant and benign mammary lesions. Most ductal carcinomas and their lymph node metastases stained more strongly with HMFG-2 whereas primary lobular carcinomas are more variable but the majority of their lymph node metastases stained more strongly with HMFG-1. Western blots of gel separated extracts of formalin fixed, paraffin embedded tumor tissue, stained with the antibodies in an ELISA assay, show that the molecular weight of components expressing the antigenic determinants varies. Smaller molecular weight components recognised by HMFG-2 and present in metastatic tumors may be lost during tissue processing. To assess the importance of the molecular weight parameter in tumor classification and prognosis it will be necessary to use frozen tissue.

Antibodies, Monoclonal↗

Sulbactam/ampicillin: effects on glucose metabolism in diabetics with soft tissue infection.

Rats and dogs chronically treated with high doses of sulbactam are known to sequester protein-bound glycogen in their hepatocytes. As a result, previous UK studies of sulbactam/ampicillin excluded patients suffering from diabetes mellitus. This study examined the effects of sulbactam/ampicillin compared to flucloxacillin/ampicillin on diabetic control, the ability to mobilize glycogen and the pancreatic beta cell response to glucagon, in diabetic patients suffering from soft tissue infection. There was no significant effect between treatment groups on any of these parameters. Sulbactam/ampicillin is unlikely to have an adverse effect on diabetic control in clinical practice when used short term in the doses employed in this study.

Ampicillin↗

A new vacuum-operated stress-providing instrument that applies static or variable duration cyclic tension or compression to cells in vitro.

An instrument providing cyclic stress to cells cultured in vitro has been developed. The unit uses a vacuum to deform a plastic Petri dish yielding 0.13% compression to cells on the inner surface, measured by strain gauge recordings. A regimen of 25 s stress and 5 min relaxation induced no significant change in synthesis of a 45 X 10(3) Mr protein that comigrates with actin, whereas a 52 X 10(3) Mr protein that comigrated with tubulin decreased from 12.7 +/- 0.451% of the total protein synthesized in control, static cells to 8.53 +/- 0.182% in stressed cells. The unit may have a broad application in monitoring biochemical changes in response to stress in cells such as muscle, lung, tendon, ligament and bone that are normally subjected to tension or compression.

Animals↗

Sonographic monitoring of hepatic cryosurgery in an experimental animal model.

Several cryosurgical techniques for freezing hepatic parenchyma have been developed. To assess the efficacy of sonographic monitoring of hepatic cryosurgery, an experimental animal model was devised. Real-time sonography was used to monitor the in vivo evolution of hypothermically induced hepatic cryolesions in four mongrel dogs. The results suggest that sonography is an effective and accurate means of monitoring the entire freezing and thawing cycle in hepatic cryosurgery.

Animals↗

Histochemical studies with a monoclonal antibody raised against a partially purified soluble estradiol receptor preparation from human myometrium.

A monoclonal antibody (D5) raised against affinity-purified cytosol estradiol receptor (REC) from human myometrium has been used to stain human tissues by means of an indirect immunoperoxidase method. Good staining was obtained with ethanol-, glutaraldehyde-, or Carnoy's-fixed material but not with formalin or Bouin's fixation. Cytoplasmic staining of human breast tumors exhibited a highly significant correlation (P less than 0.001) with REC assayed by conventional estradiol-binding assay provided that allowance was made for both staining intensity and cellularity of the tumor; no correlation existed with soluble progesterone receptor content. Both patient age and tumor differentiation influenced staining patterns in the same way as did REC content. Cultured REC-positive human breast tumor cell lines (MCF-7, ZR-75-1, and CA-2) showed positive staining as did cultured epithelium from human milk. Epithelia in normal breast and fibroadenoma exhibited variable staining that rarely reached the intensity seen in REC-positive tumor cells. The staining patterns of human normal endometrium, myometrium, fallopian tube, ectocervix, endocervix, and ovary and neoplastic endometrium and ovary are described. In every situation thus far examined only cytoplasmic staining has been observed.

Adult↗

[Pneumopathies caused by hypersensitivity to amiodarone and associated nephropathies. Study by alveolar lavage].

Four cases of amiodarone-induced restrictive, hypoxaemic lung disease are described. The cumulative dosages of amiodarone were relatively low (30 to 100 g). Alveolar lavage studies showed a lymphocytosis and study of the lymphocytic sub-populations showed an increase in the OKT8 group, and an inversion of the OKT4/OKT8 ratio. The outcome was favourable on withdrawal of amiodarone and steroid therapy. The immunological origin of this form of lung disease was confirmed. Two patients had renal failure; in the first case, hypercalcaemia, hyperphosphoremia and renal calcification were observed. The second patient had endo- and extracapillary glomerulonephritis with C3 deposits and circulating immune complexes. Renal failure regressed in both cases on withdrawal of amiodarone and with steroid therapy.

Acute Kidney Injury↗

Influence of new hydroxylated triphenylethylene (TPE) derivatives on estradiol binding to uterine cytosol.

Twelve homologous triphenyl acrylonitrile derivatives with a p-OH or p-CH3 group on one or more of the phenyl rings were synthesized in order to assess the relative influence of each position on binding to the estrogen receptor (ER) and on inhibition of prostaglandin synthetase (PGS). Their relative binding affinities (RBAs) for [3H]estradiol (E2)-labeled ER were compared at 0 and 25 degrees C in mouse and rat uterus cytosol with those of tamoxifen derivatives, cyclofenil and diethylstilbestrol. RBAs in both species were closely correlated (r = 0.92) although the RBAs were about twice as high in the mouse as in the rat. The unsubstituted skeleton had an RBA of much less than 0.1 (estradiol = 100). An OH-group in R1 or R2 (Fig. 1) engendered very low affinity whereas an OH-group in R gave rise to a compound with an RBA equivalent to that of E2, emphasizing the importance of this position in the interaction with ER. Compounds with an additional OH-group in R1 or R2 were significantly better competitors than E2. No further increase in RBA was noted with the trihydroxy derivative. The effect of the introduction of a hydrophobic CH3-group decreased affinity as expected in R, but also in position R1 unless a second OH-group was present in R2. None of the 12 test-compounds competed significantly for binding to the "anti-estrogen binding site" in rat kidney supernatant. Although polar groups were not necessary for inhibition of PGS, inhibition was enhanced by the presence of a hydroxy group in R or R1 (but not R2). Even greater inhibition was obtained by the further introduction of a CH3-group in R1 or R respectively. The conformations of these derivatives are compared to those of known estrogen ligands and anti-inflammatory agents in order to obtain further information on these protein recognition sites.

Acrylonitrile↗

The effect of various acrylonitriles and related compounds on prostaglandin biosynthesis.

We have studied the effect of nearly 90 arylacrylonitrile derivatives, and several related compounds, on the biosynthesis of prostaglandins from bovine seminal vesicle microsomes. This effect was compared to that of triarylacrylonitrile derivatives known for their inhibiting properties. Several arylacrylonitrile derivatives have also proved good inhibitors, especially certain N-trisubstituted compounds: trans (dimethylamino-4 phenyl)-3 (methoxy-4' phenyl)-2 acrylonitrile was the best inhibitor of the group, with an IC50 of 0.07 microM. The absence of carboxy groups in these derivatives precludes the application of any of the site-models proposed to date. We suggest that the electronic charges carried especially by the three aromatic rings play an important role in the inhibiting mechanism.

Acrylonitrile↗

Life-style intervention: a conceptual framework.

Improving one's life-style may improve one's health. However, there is a lack of consensus on how to promote compliance with newly adopted health habits. This paper presents a conceptual framework that individuals can learn to assess their life-styles and plan for health-behavior changes. It can also be used by professionals from different disciplines who are developing programs to teach healthy life-style choices. The framework is organized into three ideas: (1) Health status to a large extent reflects the individual's styles of living (a composite of beliefs, emotions, and action patterns). (2) These styles can be encouraged or sabotaged by the individual's support structures (relationships, environments, and equipment). (3) The change process can be seen as a series of steps that cycle through phases of readiness appraisal, decision making, experimentation, and reevaluation. clinical examples and documentation from relevant theory and research illustrate and substantiate the framework.

Health Status↗

Continuous flow apneic ventilation.

A study was designed to evaluate the adequacy of gas exchange during continuous flow apneic ventilation (CFAV) in dogs. Seventeen dogs (average weight 22.9 kg) were divided into three experimental groups. Group I (n = 7) was anesthetized, paralyzed and ventilated with air using intermittent positive pressure ventilation (IPPV) through a tracheal tube. The tube was removed and each main stem bronchus was cannulated with a 2.5 mm i.d., 4 mm o.d. polyethylene catheter using a fiberoptic bronchoscope. The tracheal tube was replaced to hold the catheters in place. Heated, humidified air was continuously delivered equally to each catheter. Total flows ranged from 8 to 28 l/min (0.4-1.4 l X kg-1 X min-1). Airway pressure (Paw) in the trachea did not exceed 2 mmHg (0.27 kPa). Adequate gas exchange in terms of arterial oxygen and arterial carbon dioxide tension (Pao2 and Paco2) was found after 30 min at flows greater than 16 l X min-1. Group II (n = 7) was managed similarly to the first group, insufflating endobronchial air using the optimal flow of 1.0 l X kg-1 X min-1 obtained from Group I. CFAV continued for 5 h in all animals. Blood gas samples and measurements of systemic blood pressure, heart rate (HR), pulmonary artery blood pressure, pulmonary artery wedge pressure, cardiac output (Qt), and temperature were taken every 30 min. Group III (n = 3) was anesthetized similarly to the other groups. Pulmonary gas distribution was evaluated in relation to catheter placement using Xe133. Results showed significant differences between Pao2 values during CFAV and IPPV; however, all animals were adequately oxygenated.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗