PubMed Health⌕ Search

Biomedical subjects

J Gilbert

Publications and source records attributed to J Gilbert.

At least 199 records · Page 11Linked to original sources

A quantitative analysis of blood-brain barrier ultrastructure in the aging human.

The unique ultrastructure of brain endothelial cells restricts nonspecific leakage of blood-borne molecules across the blood-brain barrier (bbb). Human barrier ultrastructure has not been studied extensively because of the rapid ultrastructural degeneration that takes place after death. We have obtained living, structurally normal neocortex and underlying white matter at biopsy from patients of various ages, and have quantitated ultrastructural features that are associated with the bbb so that we could characterize human barrier ultrastructure and determine whether it changes with age. We found that gray matter capillaries have thinner walls than white matter capillaries, and that during aging white matter capillary walls became thinner until they approached the dimensions of those in gray matter. Thinning is due to loss of pericytes and thinning of the endothelial cytoplasm. The mitochondrial density was found to be higher in gray matter than in white matter, but this is a consequence of there being a smaller cytoplasmic volume and not more (or larger) mitochondria. The mitochondrial population did not change with age. Presumptive nonspecific permeability routes (endothelial vesicles, junctional gaps) did not change with age; therefore we found no morphological substrate for increased nonspecific bbb permeability in the aging human. The loss of pericytes, however, suggests that the bbb in the elderly may be less able to compensate for transient leaks.

Aging↗

Studies on the metabolism of deoxynivalenol in the rat.

The metabolism and tissue distribution of [14C]deoxynivalenol have been studied in male PVG rats. Following administration of a single oral 10-mg/kg dose, radioactivity excreted in the urine and faeces accounted, respectively, for 25 and 64% of the administered dose within 96 hr. Less than 0.15% of the dose was detected in the respired air. Very little radioactivity appeared to be retained in any of the tissues examined after 96 hr. HPLC separation of several urinary and faecal metabolites was achieved on a reversed-phase column, using two different elution systems, one at neutral pH and one acidified. Two of the major non-polar HPLC peaks were identified by gas chromatography-mass spectrometry as unchanged deoxynivalenol and 3 alpha,7 alpha,15-trihydroxytrichothec-9,12-dien-8-one.

Animals↗

Intravenous sedation for cataract surgery.

Fifty-five unpremedicated outpatients scheduled for cataract surgery were randomly allocated to receive either a fixed dose of nalbuphine and methohexitone or fentanyl and diazepam administered in a dose adjusted to produce the required sedative effect. Statistical analysis revealed no difference between groups with regard to immediate side effects, intra-ocular pressure or postoperative nausea or vomiting. Recovery time from administration of the sedative until compliance with simple commands was significantly longer in the nalbuphine/morphine group (89 vs 196 seconds) but this was not felt to be of clinical importance. This combination was better in terms of sedation at the time of insertion of the nerve blocks, lack of recall of insertion of the nerve block, incidence of intra-operative complications, surgeon's assessment of operating conditions and patient acceptability. This fixed dose by weight drug combination for intravenous sedation should be applied widely.

Adolescent↗

Critical care management of the patient with acute spinal cord injury.

The critical care management of acute injury to the cervical spinal cord is discussed from the perspective of the pathophysiology of the injury process and its ramifications. Emphasis is placed upon resolution of cardiovascular derangements, spinal cord resuscitation, and respiratory support utilizing practical therapeutic interventions.

Acute Disease↗

Method for the analysis in maize of the Fusarium mycotoxin moniliformin employing ion-pairing extraction and high-performance liquid chromatography.

The Fusarium mycotoxin moniliformin (hydroxycyclobutenedione) has been determined in maize using a novel method with a recovery of 70-80% at 400-1600 micrograms/kg and 60% at the detection limit of 100 micrograms/kg. The method requires extraction of the toxin into aqueous tetra-n-butylammonium hydroxide and removal of cations from this solution by ion-exchange chromatography. Following clean-up by partitioning against dichloromethane, further quaternary ammonium reagent was added to the aqueous phase which was absorbed onto a hydrophilic matrix and the tetra-n-butylammonium moniliformate ion pair extracted into dichloromethane. After evaporation of the organic eluent, the residue was dissolved in aqueous sodium chloride and moniliformin quantitated by ion-pair high-performance liquid chromatography with UV detection. A batch of five samples may be analysed in 5-6 h including the chromatographic determination.

Chromatography, High Pressure Liquid↗

Comparison and critical evaluation of six published extraction and clean-up procedures for aflatoxin M1 in liquid milk.

A practical evaluation has been carried out of six previously published extraction and clean-up methods for aflatoxin M1 in liquid milk. The procedures evaluated incorporated the most widely used stages of clean-up including solvent extraction and silica gel chromatographic clean-up, selective solvent extraction of the extracted residue, the use of deproteination prior to hydrophilic column liquid-liquid partition or solvent extraction and the use of pre-packed reversed-phase cartridges for the direct extraction of aflatoxin M1 from the milk. Analysis times for each method, recoveries and relative costs are reported together with fluorescence high-performance liquid chromatography chromatograms, obtained under identical conditions to compare the relative cleanliness of the final extracts produced by each method. A pre-packed reversed phase cartridge method was shown to be the most satisfactory in terms of speed, cost and cleanliness of the final residue.

Aflatoxin M1↗

Elevated gamma-aminobutyric acid level in striatal but not extrastriatal brain regions in Parkinson's disease: correlation with striatal dopamine loss.

We measured the concentration of gamma-aminobutyric acid (GABA), glutamic acid, and o-phosphoethanolamine in autopsied brain of 9 patients who died with idiopathic Parkinson's disease and 10 control subjects. In the control striatum GABA showed an uneven rostrocaudal distribution pattern with rostral subdivisions containing about 40 to 50% higher levels. When compared with controls, GABA concentrations in Parkinson's disease striatum were generally elevated. The GABA elevation was most pronounced in the caudal subdivision of the putamen; this striatal subdivision also showed the most severe dopamine loss. We observed in the caudal putamen a significant negative correlation between the (elevated) GABA and (reduced) dopamine levels (the latter expressed as the sum of dopamine plus 3-methoxytyramine). Milder nonsignificant elevations of GABA levels were observed in intermediate and rostral putamen followed by the caudate head subdivisions. GABA levels were normal in all extrastriatal brain areas examined. Striatal glutamic acid levels were markedly elevated in 3 of the 9 patients with Parkinson's disease. We suggest that the altered GABA metabolism in the striatum, especially the putamen, is consequent to the nigrostriatal deficiency in this disorder. This secondary change in striatal GABA function is likely to contribute to the basal ganglia dysfunction produced by the striatal dopamine loss and thus may be related to certain aspects of parkinsonian symptomatology.

Brain Chemistry↗

Screening, confirmation, and quantification of sulphonamide residues in pig kidney by tandem mass spectrometry of crude extracts.

Collisionally activated dissociation mass spectra, observed with a hybrid tandem instrument, of the chemical ionization protonated molecular ions of sulphonamide drugs have been used as the basis of a rapid screening procedure for these drugs in crude extracts of pig's kidney by scanning to detect the parents of a characteristic daughter fragment. Extracts were introduced without chromatography by a moving belt interface. Detection limits of 0.1 mg/kg were achieved. Confirmation was made by obtaining daughter ion spectra of the protonated molecular ions. Multiple reaction monitoring with a stable isotope analogue as internal standard permitted the quantification of targeted compounds with high sensitivity and precision.

Animals↗

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↗