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Biomedical subjects

J Jenner

Publications and source records attributed to J Jenner.

18 recordsLinked to original sources
PubMed2004

Glycosylation and lectins-examples of immunesurveillance and immune evasion.

Cell surface proteins are posttranslationally modified by tightly regulated enzymes of glycosylation. Typical patterns of glycosylation may signal pathological situations to the immune system. Here, carbohydrate receptors on the surface of cells in the immune system are involved in regulation of effector cells. Moreover, some lectins are circulating in the plasma and take part in host defense. The code of carbohydrate modifications is impaired in malignant cells and yet they are not eliminated. In this review, we focus on recent experimental evidence for regulatory functions of lectins and carbohydrate derivatives in the immune system and tumours.

Animals↗
PubMed2001

The effect of hexafluorocyclobutene on rat bronchoalveolar lavage fluid surfactant phospholipids and alveolar type II cells.

Hexafluorocyclobutene (HFCB), a reactive organohalogen gas, causes overwhelming pulmonary oedema. We investigated its effect on the rat lung surfactant system, comparing its action on type II pneumocytes with air-exposed rats. The inflammatory cell population and protein content of bronchoalveolar lavage fluid was analysed following exposure to air or HFCB (LCt30). Six rat lung phospholipids were measured by high-performance liquid chromatography, following solid phase extraction (SPE) from lavage fluid. Transmission electron microscopy (TEM) was used to visualise effects on alveolar type II cell ultrastructure. HFCB caused changes in cell populations and increased lavage fluid protein compared to controls, suggesting a permeability oedema. Changes in the total amount and percentage composition (sustained decrease in phosphatidylglycerol and phosphatidylcholine) of surfactant phospholipids also occurred. TEM observations indicated no direct ultrastructural damage to the type II cells, but showed initial, rapid release of surfactant into the alveolar space. HFCB altered the surfactant system in a manner similar to that shown following another reactive organohalogen gas, perfluoroisobutene (PFIB), but differently to that after phosgene. These differences suggest different mechanisms of action even though pulmonary oedema is the final injury for all gases. Better knowledge of the mechanisms involved will improve prospects for prophylactic/therapeutic intervention.

Animals↗
PubMed1999

Chronic compartment syndrome affecting the lower limb: MIBI perfusion imaging as an alternative to pressure monitoring: two case reports.

Intracompartmental pressure monitoring remains the primary method of diagnosing chronic compartment syndrome. MIBI perfusion imaging is widely available and offers a radionuclear imaging technique for diagnosing this condition. Although the results are not identical with those from pressure monitoring, MIBI may offer a useful screening test for this condition.

Adult↗
PubMed1999

The effect of perfluoroisobutene and phosgene on rat lavage fluid surfactant phospholipids.

1. This study investigated whether the reactive organohalogen gases perfluoroisobutene (PFIB) and phosgene, which cause death by overwhelming pulmonary oedema, affect the surfactant system or type II pneumocytes of rat lung. 2. The progression and type of pulmonary injury in Porton Wistar-derived rats was monitored over a 48 h period following exposure to either PFIB or phosgene (LCt30) by analyzing the inflammatory cells and protein in bronchoalveolar lavage fluid. Six rat lung phospholipids were measured by high-performance liquid chromatography, following solid phase extraction from lavage fluid. 3. Alterations in the cell population and lung permeability occurred following both gases, indicating that the injury was a permeability-type pulmonary oedema. Changes in the total amount of phospholipid and in the percentage composition of the surfactant were different for the two gases. PFIB produced increases in phosphatidylglycerol and phosphatidylcholine over the first hour, similar to that seen following air exposure, followed by substantial decreases in these phospholipids. Phosgene caused late increases in all phospholipids from 6 h post-exposure. 4. Differences in the response of the surfactant system to exposure to PFIB and phosgene suggest different mechanisms of action at the alveolar surface although the final injurious response is pulmonary oedema for both gases.

Administration, Inhalation↗
PubMed1995

Effect of vitamin C supplementation on lipoprotein cholesterol, apolipoprotein, and triglyceride concentrations.

Plasma ascorbic acid (AA) frequently is positively correlated with high-density-lipoprotein (HDL) cholesterol and inversely related to total cholesterol concentration. To determine if vitamin C intake can alter cholesterol concentration, we examined the effect of vitamin C supplementation (1 g/d) on lipoprotein cholesterol and triglyceride levels in 138 subjects, aged 20 to 65 years, who completed an 8-month randomized, double-blinded, placebo-controlled trial. Individuals with higher levels of plasma AA (> 80 mumol/L for men and > 90 mumol/L for women), HDL cholesterol (> 1.4 mmol/L for men and > 1.7 mmol/L for women), and total cholesterol (> 6.7 mmol/L) were excluded from this trial. We observed no overall effect of supplementation on plasma concentrations of HDL, LDL, or total cholesterol, apolipoprotein (apo) B, or triglyceride. We did observe a marginally significant (P < 0.10) increase of 1.9 mumol/L (5.3 mg/dL) in apo A-I concentration with supplementation and a significant (P < 0.05) difference of 0.10 mmol/L (3.8 mg/dL) in HDL cholesterol concentration between vitamin C and placebo treatment in a nonrandomized subgroup of individuals (n = 43) and a baseline plasma AA level less than 55 mumol/L. Although the apo A-I concentration increase was only marginally significant with supplementation, change in plasma AA concentration was significantly (P < 0.05) correlated with change in apo A-I concentration in the entire sample. The overall results of this trial were negative, but our data do not allow us to rule out the possibility that vitamin C supplementation might increase HDL cholesterol or apo A-I concentrations among individuals with lower plasma AA levels.

Adult↗
PubMed1995

Transdermal delivery of physostigmine. A pretreatment against organophosphate poisoning.

Physostigmine absorption through isolated human skin and inhibition of plasma and red blood cell cholinesterases in guinea-pigs have been measured to assess the feasibility of its transdermal delivery as a pretreatment for organophosphate poisoning. Penetration of radiolabelled physostigmine across human epidermis was measured in-vitro using glass diffusion cells and optimization of physostigmine delivery was achieved by changes in vehicle formulation and use of penetration enhancers. Two-component vehicles consisting of propionic acid/isopropyl myristate (50:50) and propionic acid/oleic acid (50:50) produced the highest transdermal delivery of physostigmine. A comparison of formulations containing propionic acid alone with propionic acid plus oleic acid when applied to guinea-pigs, showed that inclusion of oleic acid allowed the amount of physostigmine and the size of the transdermal patch to be substantially reduced, whilst maintaining effective delivery rates. The formulation containing oleic acid was not irritant to guinea-pigs when applied to the skin for 48 h. It is concluded that a mixture of propionic acid and oleic acid containing physostigmine is a good candidate for transdermal delivery of physostigmine as a pretreatment for organophosphate poisoning.

Administration, Cutaneous↗
PubMed1995

Effects of alcohol consumption on lipoproteins of premenopausal women. A controlled diet study.

A substantial portion of American women consume alcohol, but controlled studies of alcohol-induced changes in lipoproteins of women are rare. In this study, the effects of alcohol consumption (equivalent to two drinks per day) on the lipoprotein profiles of 34 premenopausal women were measured while controlling subjects' diet and various other potentially confounding variables including phase of the menstrual cycle. Alcohol and no-alcohol treatments were administered in a crossover design, and blood samples were obtained during the early follicular phase of the third month of treatment. With alcohol, HDL cholesterol levels increased 10%, LDL levels decreased 8%, and levels of lipoprotein(a) were unchanged. The increase in HDL cholesterol was due to an increase in both HDL2 and HDL3, and the overall size of HDL particles was increased. HDL particles containing apolipoprotein (apo) A-I and apoA-II as well as those containing apoA-I but no apoA-II were elevated in response to alcohol. Although these observations are limited to a single phase of the menstrual cycle, the alcohol-induced changes in lipoproteins are consistent with changes that are thought to confer protection against coronary heart disease.

Adult↗
PubMed1994

Lipoprotein(a) and coronary heart disease.

Elevated plasma or serum lipoprotein(a) (Lp(a)) levels have been associated with premature coronary heart disease (CHD). Lp(a) levels can be assessed quantitatively by electrophoresis and quantitatively by immunoassays determining either total Lp(a) mass, apo(a) mass on Lp(a) protein mass, or by precipitation methods followed by measurement of Lp(a) cholesterol. We prefer the latter method because it can be standardized. Electrophoretic methods can detect total Lp(a) values > or = 30 mg/dl. These values correspond to Lp(a) cholesterol values > or = 10 mg/dl. Such values are above the 75th percentile and represent high risk values for CHD. Values above the 90th percentile for middle aged men and women in Framingham (n = 2678) are > or = 38 mg/dl for total Lp(a). About 16% of patients with premature CHD (n = 321) have such values and have familial Lp(a) excess. Lp(a) is atherogenic because it can be deposited in the arterial wall, and it also can interfere with fibrinolysis. Multiple apo(a) isoforms have been found and are due to a variable number of kringle 4 like repeats. Lower molecular weight apo(a) isoforms forms are associated with elevated Lp(a) values and are more frequent in CHD kindreds. Both Lp(a) levels and apo(a) isoforms are highly heritable in this Caucasian population. Lp(a) values can be decreased with niacin, and such therapy should be strongly considered in CHD patients with elevated Lp(a) levels (> or = 30 mg/dl) since niacin treatment has been shown to decrease CHD morbidity and mortality in unselected CHD patients.

Adolescent↗
PubMed1994

Coordination of aimed movements in a case of unilateral cerebellar damage.

We have studied multi-joint arm movements in a patient with right cerebellar damage. Our patient's kinetic tremor was reduced in the absence of visual feedback, but increased when performing a concurrent cognitive task. We suggest that her kinetic tremor reflects use of a slow cortical feedback circuit for error-corrections during movement. Analysing the spatial relation between hand aperture and hand transport in prehensile movements, we found preserved strategic, trial-to-trial coordination, but impaired reactive, within-trial coordination. We conclude that the proprioceptive representations provided by the normal cerebellum play an important role in coordinating multi-joint movement.

Adult↗
PubMed1992

Familial lipoprotein disorders in patients with premature coronary artery disease.

BACKGROUND: Genetic lipoprotein disorders have been associated with premature coronary artery disease (CAD). METHODS AND RESULTS: The prevalence of such disorders was determined in 102 kindreds (n = 603 subjects) in whom the proband had significant CAD documented by angiography before the age of 60 years. Fasting plasma cholesterol, triglyceride, low density lipoprotein (LDL) cholesterol, apolipoprotein (apo) B, and lipoprotein (a) [Lp(a)] values above the 90th percentile and high density lipoprotein (HDL) cholesterol and apo A-I below the 10th percentile of age- and sex-specific norms were defined as abnormal. An abnormality was noted in 73.5% of probands compared with 38.2% in age-matched controls (p less than 0.001), with a low HDL cholesterol level (hypoalphalipoproteinemia) being the most common abnormality (39.2% of cases). In these kindreds, 54% had a defined phenotypic familial lipoprotein or apolipoprotein disorder. The following frequencies were observed: Lp(a) excess, 18.6% (includes 12.7% with no other dyslipidemias); hypertriglyceridemia with hypoalphalipoproteinemia, 14.7%; combined hyperlipidemia, 13.7% (11.7% with and 2.0% without hypoalphalipoproteinemia); hyperapobetalipoproteinemia (elevated apo B only), 5%; hypoalphalipoproteinemia, 4%; hypercholesterolemia (elevated LDL only), 3%; hypertriglyceridemia, 1%; decreased apo A-I only, 1%. Overall, 54% of the probands had a familial dyslipidemia; unclassifiable lipid disorders (spouse also affected) were found in 3%. No identifiable familial dyslipidemia was noted in 43% of kindreds of those; nearly half (45%) had a sporadic lipid disorder. Parent-offspring and proband-spouse correlations for these biochemical variables revealed that lipoprotein and apolipoprotein levels are in part genetically determined, with Lp(a) showing the highest degree of parent-offspring correlation. CONCLUSIONS: Our data indicate that more than half of patients with premature CAD have a familial lipoprotein disorder, with Lp(a) excess, hypertriglyceridemia with hypoalphalipoproteinemia, and combined hyperlipidemia with hypoalphalipoproteinemia being the most common abnormalities.

Coronary Disease↗
PubMed1988

Xenobiotic metabolism in the nasal epithelia.

The nasal epithelia in several species contains fairly high levels of drug metabolising enzymes, and in many cases the site specific toxicities of chemicals are due to their metabolic activation in the nasal tissues. This article reviews some of the current literature on the metabolic capacities of nasal epithelia, in particular the distribution and characteristics of cytochrome P-450 isozymes. In addition to the role of these nasal enzymes in metabolism of inhaled xenobiotics, other possible biological roles for these enzymes are also discussed.

Animals↗
PubMedDate not supplied

Human skin absorption of Bis-2-(chloroethyl)sulphide (sulphur mustard) in vitro.

The purpose of this study was to measure the absorption and intra-epidermal fate of 35S-radiolabelled sulphur mustard (35SM) in human breast skin in vitro. Skin (full-thickness or heat-separated epidermis) was placed into static diffusion cells and was exposed to droplets of liquid 35SM or saturated 35SM vapour. Amounts of 35SM penetrating the skin were measured from which skin absorption rates were calculated. Unbound radiolabel was washed from the surface, extracted from the skin and analysed to determine the identity of the radiolabelled species in order to measure the extent of hydrolysis of sulphur mustard. Penetration rates of liquid 35SM measured in vitro (71-294 microg cm(-2) h(-1)) were in agreement with those measured previously in vivo using human volunteers (60-240 microg cm(-2) h(-1)). Rates of liquid 35SM skin absorption under occluded, infinite dose conditions were highest through heat-separated epidermal membranes (294+/-58 microg cm(-2) h(-1)) and lowest through full-thickness skin (71+/-14 microg cm(-2) h(-1)). Fluxes of saturated 35SM vapour (110+/-75 microg cm(-2) h(-1)) through heat-separated membranes were similar to those previously measured through human forearm skin in vivo (162 microg cm(-2) h(-1)). Although hydrolysis of 35SM did occur, both on the surface and within the skin, it accounted for only a small percentage of the total applied dose (<2.7+/-1.2%). The difference in total amount of liquid 35SM penetrated between occluded and unoccluded conditions in vitro (79+/-14%) was similar to that lost as vapour from unoccluded skin in vivo (80%). A substantial reservoir of 35SM (14-36% of the applied dose) was measured within heat-separated epidermal membranes for up to 24 h which may have significant implications for the management of personnel exposed to sulphur mustard.

Autoradiography↗
PubMedDate not supplied

In vitro skin absorption and decontamination of sulphur mustard: comparison of human and pig-ear skin.

The aim of this study was to evaluate the use of an in vitro skin diffusion cell system as a model for assessing decontaminants against the chemical warfare agent sulphur mustard (SM). The in vitro absorption rates of SM through heat-separated human (157 +/- 66 microg cm(-2) h(-1)) and pig-ear (411 +/- 175 microg cm(-2) h(-1)) epidermal membranes were in agreement with previous in vivo studies that quoted skin absorption rates of 150 and 366 microg cm(-2) h(-1), respectively. Decontaminants (fuller's earth, Ambergard and BDH spillage granules) were ranked in order of effectiveness by measuring the skin absorption rates and the percentage of applied dose of SM that penetrated human and pig-ear epidermal membranes. The effectiveness of fuller's earth measured in this in vitro study using human epidermal membranes was in agreement with a previous in vivo human volunteer study. Similarly, the effectiveness of fuller's earth and Ambergard measured in vitro with pig-ear epidermal membranes was in agreement with a previous in vivo study conducted on rats. However, there was complete disparity in the ranking of decontaminants between human and pig-ear epidermal membranes measured in vitro. Thus, although pig-ear skin may be a relatively good model for predicting the human skin absorption of SM, it is a poor model for testing decontamination systems. The results of this study further validate the use of Franz-type glass diffusion cells containing human epidermal membranes as a model for predicting in vivo human skin absorption.

Aluminum Compounds↗