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Biomedical subjects

J Gillespie

Publications and source records attributed to J Gillespie.

At least 19 recordsLinked to original sources
PubMed1992

Production of an extracellular toxin by the oral pathogen Campylobacter rectus.

The ATCC type strain and six clinical isolates of Campylobacter rectus were tested for toxicity against HL-60 cells and human polymorphonuclear neutrophils (PMNs). After challenge with bacterial cell suspensions and media supernatants for up to 4 h, eukaryotic cell viability was assayed by trypan blue dye exclusion and lactate dehydrogenase release. Cells of the C. rectus type strain were not toxic. However, ethanol and (NH4)2SO4 extracts of culture media supernatants killed HL-60 cells in a time and dose dependent manner with 700 micrograms of supernatant protein killing 100% of HL-60 cells in 4 h. Concentrated media supernatants from clinical isolates also killed 100% of HL-60 cells in 30 to 60 min. The bacterial culture supernatants were toxic to PMNs with clinical isolates killing 70 to 90% of PMNs in 2 to 4 h. SDS-PAGE and immunoblot analysis of the toxic media supernatants revealed C. rectus specific proteins and lipopolysaccharide (LPS). The toxic activity was inhibited by protease, indicating that the toxin was protein. Non-toxic and toxic media supernatants were obtained by altering hemin and fumarate in the growth media. SDS-PAGE analysis of these revealed that all toxic supernatants contained a 104 kDa protein.

Bacterial Toxins↗
PubMed1992

Human pancreatic cancer cell lines do not express receptors for somatostatin.

The in vivo administration of somatostatin (SS) or its analogues is capable of suppressing the growth of pancreatic cancer in experimental animals. We examined the effects of SS-14 and its analogue RC-160 on the in vitro growth of two human pancreatic cancer cell lines MiaPaCa-2 and Panc-1 stimulated with epidermal growth factor (EGF) or insulin-like growth factor 1 (IGF-1). Neither SS-14 nor RC-160 inhibited the growth of either cell line. In contrast RC-160 did inhibit the EGF-stimulated growth of a rat pancreatic cancer cell line AR42J. Binding studies with 125I-Tyr11 somatostatin revealed the presence of a single class of high affinity binding sites with a Kd of 0.20 +/- 0.05 nM and a Bmax of 2.1 +/- 0.26 pmoles mg-1 protein on AR42J but not displaceable binding was observed on MiaPaCa-2 or Panc-1. We conclude that lack of receptors accounts for the failure of SS-14 and RC-160 to influence the growth of human pancreatic cancer in vitro. These results, taken together with other findings, lead us to question the therapeutic efficacy of somatostatin and its analogues as mono-therapy in the treatment of human pancreatic cancer.

Animals↗
PubMed1992

Effects of bile salt infusion on chlorpromazine-induced cholestasis in the isolated perfused rat liver.

The present study has demonstrated that tauroursodeoxycholate (TUDC), but not taurocholate, can reverse chlorpromazine (CPZ)-induced cholestasis in the isolated perfused rat liver. At an infusion rate of 1.5 mumol/min, TUDC led to restoration of bile flow in the perfused rat liver made cholestatic by the addition of 250 microM CPZ. This reversal was accompanied by an increased excretion of CPZ and its metabolites. A higher infusion rate of 5.0 mumols TUDC/min, however, led to only a transient increase in bile flow and to no increase in CPZ excretion. In contrast to the effects of TUDC, infusion of taurocholate led to an exacerbation of CPZ-induced cholestasis. The differences in the efficacy of the two bile salts may be due to their relative detergent (hydrophobic) properties.

Animals↗
PubMed1992

Drug-induced cholestasis in the perfused rat liver and its reversal by tauroursodeoxycholate: an ultrastructural study.

Chlorpromazine at a concentration of 250 microM and estradiol-17 beta-D-glucuronide at 17.5 microM on infusion led to a sharp reduction in bile flow by the in vitro perfused rat liver. This was accompanied by fragmentation and a loss of canalicular microvilli, dilatation of canaliculi, and thickening of pericanalicular ectoplasm. Less prominent were the smooth endoplasmic reticulum dilatation, lysosomal lamination, and the appearance of amorphous bile in hepatocyte cytoplasm. The bile flow and electron microscopy appearance were restored to normal by infusion of tauroursodeoxycholate in a concentration of 5 mumols/min for the estradiol-17 beta-D-glucuronide-induced cholestasis and 1.5 mumol/min for the chlorpromazine-induced cholestasis. Changes in ultrastructure paralleled changes in bile flow. These observations demonstrate the feasibility of electron microscopy studies on the perfused liver, and the rapidity with which cholestatic changes appear.

Animals↗
PubMed1991

The vacuolar H(+)-translocating ATPase of renal tubules contains a 115-kDa glycosylated subunit.

Kidney microsomes were fractionated with Triton X-114, to give a fraction enriched in the renal tubule H(+)-translocating ATPase, as judged by the sensitivity of its ATPase activity to bafilomycin A1, and its content of two polypeptides recognized by antibodies directed against subunits of plant tonoplast ATPases. This fraction contained a polypeptide of apparent molecular mass of 115 kDa, that was recognized by an antibody to the largest (120 kDa) subunit of chromaffin-granule membrane H(+)-ATPase, and, like this subunit, was reduced in molecular weight on treatment with glycopeptidase F. We conclude that, like other mammalian vacuolar H(+)-ATPases, the kidney H(+)-ATPase contains a large, glycosylated subunit.

Adrenal Gland Neoplasms↗
PubMed1991

Biology of pancreatic cancer.

Pancreatic cancer is the fifth leading cause of death from malignant disease in Western society. Apart from the fortunate few patients who present with a resectable small pancreatic adenocarcinoma, conventional treatment offers no hope of cure and has little palliative value. Over the past two decades major steps have been made in our understanding of the biology of pancreatic growth and neoplasia. This review sets out to explore these advances, firstly in the regulation of normal pancreatic growth, and secondly the mechanism which may be involved in malignant change of the exocrine pancreas. From an understanding of this new biology, new treatment strategies may be possible for patients with pancreatic cancer.

Animals↗
PubMed1991

Axotomy-induced changes in rabbit hindlimb nerves and the effects of chronic electrical stimulation.

Chronic electrical stimulation and extracellular recording combined with morphological examination of nerves in this study provided a detailed description of the time course and extent of fiber atrophy when the trophic influence of the target was removed by ligation of axotomized nerves and neural activity was replaced by chronic stimulation. The major findings are that decline in amplitude of compound action potentials (CAPs) and fiber diameters is rapid after axotomy and is not reversed or prevented by chronic electrical stimulation, as would be predicted if neural activity played an essential role in maintaining normal fiber caliber. Chronic stimulation had a small short-term sparing effect in the first month after axotomy but was counterproductive over long periods. Comparison of the time course of the decline in CAP amplitude and reduction of fiber diameters with described alterations in mRNA expression of neurofilament protein indicates that the early atrophy is too rapid to be accounted for by reduced synthesis and transport of neurofilaments. It is more likely to result from modification of axonal proteins after axotomy. Replacement of neural activity with stimulation may reduce the initial atrophy but, over longer periods, exacerbates the atrophy, possibly by affecting the synthesis and transport of cytoskeletal proteins. These studies show that the trophic control of nerve fiber size is mediated primarily by functional contacts with peripheral targets and that neural activity plays a relatively small role. Without functional contacts, nerve fibers decline in diameter to stable but lower values. The atrophy was exacerbated by imposing neural activity on the relatively quiescent axotomized neurons.

Action Potentials↗
PubMed1989

The impact of paired motor unit discharges on tremor.

We studied paired discharges (PDs) of single motor units (MUs) of the first dorsal interosseus muscle in parkinsonian and essential tremor. The number of PDs increased with increasing tremor strength and the duration of their intervals shortened. The amplitudes of the single tremor beats showed a significant negative correlation to the duration of the intervals of the preceding PDs. It is concluded that PDs play an important role as tremor amplifiers. The basic mechanism is probably the more than linear summation of two twitch contractions with short interval which is known from animal experiments.

Adult↗
PubMed1988

Influence of oxygen tension on the respiratory activity of Mycobacterium phlei.

Growth of Mycobacterium phlei under low oxygen tension resulted in specific activities two to twenty times lower for formate dehydrogenase, malate dehydrogenase, beta-hydroxybutyrate dehydrogenase, lactate oxidase and NADH dehydrogenase than when cultures were grown under high aeration. An increase in fumarate reductase and succinate dehydrogenase occurred with M. phlei grown under low oxygen tension. Malate: vitamin K dehydrogenase and glucose-6-phosphate dehydrogenase activity were not significantly affected by the oxygen tension used to grow the bacteria, and neither culture contained a lactate dehydrogenase. With growth of M. phlei in conditions of low oxygen tension, cytochrome a was not detected, but cytochrome b was prominent in membranes and cytochrome c was present in the soluble fraction.

Aerobiosis↗
PubMed1988

Chemical and biological characterization of the lipopolysaccharide of the oral pathogen Wolinella recta ATCC 33238.

To investigate the potential pathogenic mechanisms of the oral periodontopathogen Wolinella recta ATCC 33238, we have isolated its lipopolysaccharide (LPS) and determined the chemical composition and selected in vitro biological activities of the molecule. Sodium desoxycholate-polyacrylamide gel electrophoresis revealed the W. recta LPS to be an atypical smooth LPS with short O-antigenic side chains. Chemically the LPS consisted of 47.2% lipid A, 19.6% polysaccharide, 9.0% heptose, 8.5% hexosamine, 3.2% phosphate, and 0.6% 2-keto-3-deoxyoctanoate. The major fatty acids were hexadecanoic acid (25.0%), 3-OH tetradecanoic acid (23.8%), tetradecanoic acid (15.4%), 3-OH hexadecanoic acid (11.6%), and octadecenoic acid (10.9%). Rhamnose constituted 87.8% of the carbohydrates generally associated with the O antigen, with smaller amounts of glucose (5.5%), mannose (4.9%), and an unidentified sugar (1.9%). CD-1 and C3H/HeN macrophages (M phi) exposed to 1 microgram of W. recta LPS per ml released 6.0 and 10.5 ng of prostaglandin E per ml of supernatant, representing 625% and 1,306% of prostaglandin E release by the control (without LPS). Maximum prostaglandin E release occurred in CD-1 M phi exposed to 100 micrograms of LPS per ml and was equivalent to 1,542% of release by the control. Interleukin-1 (IL-1) activities in CD-1 and C3H/HeN M phi exposed to 1 micrograms of LPS per ml were 257% and 1,941% of activities in the control, respectively. Maximum IL-1 release in CD-1 M phi occurred in response to 50 micrograms of LPS per ml and represented a 927% increase over release in the control, while 100 micrograms LPS per ml stimulated maximum IL-1 release in C3H/HeN M phi that was greater than 5,000% of release by the control.

Acid Phosphatase↗
PubMed1988

Models of spinal cord injury: Part 3. Dynamic load technique.

Having previously studied a static load model of cord injury in rats, we report here an evaluation of a dynamic (weight drop) technique. Under general anesthesia, Sprague-Dawley rats were subjected to a laminectomy at T12, after which a 10-g weight was dropped onto a force transducer and impounder resting on the spinal cord; the weight drop distances varied in different groups from 0 (control) in increments of 2.5 cm to a maximal height of 17.5 cm. A strain gauge attached to the force transducer yielded an oscilloscopic wave form from which force of impact (peak force and impulse) was calculated. Eighty-six animals were used in this parametric study. The animals were observed for 4 weeks postinjury with two tests of motor recovery (Tarlov score for locomotion and the inclined plane test). After sacrifice at 4 weeks, the spinal cords were removed and, with the use of preset criteria, qualitative histopathological scoring of the extent of tissue damage was carried out. We found that the variable height of weight drop was capable of producing a graded injury that correlated with the force of injury (as measured by the force transducer) and with the outcome parameters of functional recovery and degree of morphological damage in the spinal cord. Histopathologically, there was a tendency to central cavitation of the cord. Both the static load and the dynamic load techniques seem to be valid models of spinal cord injury. Pathologically, however, the tissue damage after static load injury involved primarily the dorsal half of the cord. By contrast, the dynamic load technique produced central cavitation comparable to that observed in human spinal cord injury. In this respect, the dynamic model seems to be superior and its use is therefore recommended for studies of therapeutic intervention for spinal cord injury.

Animals↗
PubMed1987

A new electrocardiographic classification for post-myocardial infarction clinical trials.

A new electrocardiographic code was developed for clinical trials involving patients with acute myocardial infarction (AMI). In the Multicenter Post-Infarction Program (MPIP), the electrocardiogram, classified by the Minnesota code, was not useful as a clinical predictor and played almost no role in subsequent analysis. To test its value the new code was applied to the electrocardiograms of 653 of the 866 patients in the MPIP data base who had sustained a first AMI. The MPIP code identifies AMI by region and severity. The 4 regions are anterior, lateral, inferior and posterior, defined by traditional criteria. Severity codes include Q-wave and non-Q-wave AMI, ST depression and no ischemic changes. The interpretation for each of 4 regions results in a 4-digit location severity code that is amenable to sorting and analysis. Fourteen separate and mutually exclusive groups were identified. Mortality gradients were found within the inferior AMI groups, but not within the anterior AMI groups. Mean ejection fraction was 50% for patients with isolated anterior infarction and decreased progressively (p less than 0.0003) as the extent of lateral wall involvement increased. For isolated inferior AMI, mean ejection fraction was 53%; lateral or posterior involvement did not significantly change this. The MPIP code is easy to apply, correlates acceptably well with clinically relevant variables of left ventricular function and permits the electrocardiogram to be used as a clinical predictor in large clinical trials.

Clinical Trials as Topic↗