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Biomedical subjects

J Gillespie

Publications and source records attributed to J Gillespie.

At least 37 records · Page 2Linked to original sources

Health care costs of obesity in New Zealand.

OBJECTIVE: To estimate the costs of health care that are attributable to obesity in New Zealand. METHODS: The 1991 health care costs of non-insulin dependent diabetes, coronary heart disease, hypertension, gallstone disease, post-menopausal breast cancer and colon cancer were estimated and multiplied by the population attributable factor for obesity for each condition. The relative risk estimates were taken from the literature, the obesity prevalence from a 1990 New Zealand survey, and the costs and volumes of services were taken from a variety of sources and covered hospital (inpatient and outpatient) services, general practitioner consultations, pharmaceuticals, laboratory tests and ambulance services. Calculations were conservative and net of goods and services tax. RESULTS: A conservative estimate of the health care costs attributable to obesity for the six conditions was NZ$135 million. This represents about 2.5% of total health care costs which is similar to analyses from other countries. CONCLUSIONS: The health care costs of obesity as estimated are considerable. However, the total cost of overfatness to the New Zealand population is far greater than this because lesser degrees of overfatness, the health care costs of other obesity-related conditions such as arthritis, the costs to individuals of weight-loss programs and the indirect and intangible costs were not included in the analysis. A substantial and wide-ranging public health effort is needed to turn around the increasing prevalence and costs of obesity.

Adult↗

Menthol and nonmenthol cigarettes and smoke exposure in black and white women.

Purposes of this investigation were to compare smoke constituent exposure (CO and nicotine boosts) and smoking topography parameters between black and white women, and between women regularly using menthol or nonmenthol cigarettes. A two-factor factorial design with a sample of 37 women stratified by race and menthol or nonmenthol cigarette use was implemented. There were significant main and interaction effects of race and menthol/nonmenthol use on CO boost. Black women had a mean CO boost of 10.1 ppm vs. 7.2 ppm for white women, while women using nonmenthol cigarettes had a higher CO boost (mean = 10.6 ppm) compared to those regularly using menthol cigarettes mean = 6.5 ppm). White menthol smokers had the lowest CO boost of all subgroups. There was a trend for black women to have higher nicotine boost than white women (21.4 ng/ml vs. 15.9 ng/ml). Black women had nonsignificantly higher puff volumes compared to white women (mean = 48.4 vs. 43.5 ml), while nonmenthol smokers had nonsignificantly higher puff volumes than menthol smokers (mean = 48.5 vs. 42.7 ml). Lower CO boost with mentholated cigarettes suggests factors beyond mentholation may affect elevated smoke constituent exposure among black women.

Adult↗

Expression of a suppressive p15E-related epitope in colorectal and gastric cancer.

mRNA for the suppressive epitope of p15E was found to be present in 24 of 30 samples of human colorectal cancer and in all four specimens of gastric cancer. mRNA for p15E was seldom seen in nonmalignant colonic or gastric mucosa but, when present, was associated with inflammatory or pre-malignant conditions of the digestive tract. Synthetic peptides derived from the conserved p15E sequence were found to suppress some aspects of the immune response implicated in anti-tumour activity. These data suggest that a p15E-related material with immunomodulatory properties is elaborated within human tumours, either by the tumour itself or as a normal component of the endogenous anti-tumour reaction.

Base Sequence↗

Inhibition of pancreatic cancer cell growth in vitro by the tyrphostin group of tyrosine kinase inhibitors.

Tyrphostins are a group of low molecular weight synthetic inhibitors of protein tyrosine kinases (PTK). The intracellular domains of the receptors for epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), insulin-like growth factor 1 (IGF-1) possess PTK activity. Since EGF, TGF-alpha and IGF-1 are considered to play an important role in the proliferation of pancreatic cancer cells, we studied the effects of tyrphostins on the growth of three human pancreatic cancer cell lines (MiaPaCa-2, Panc-1 and CAV). The tyrphostins AG17, T23 and T47 all inhibited EGF and serum-stimulated DNA synthesis. AG17 was found to be the most potent of these agents and caused a dose-dependent but reversible inhibition of cell growth. Furthermore using an immunoblotting procedure we also found AG17 to inhibit EGF-induced tyrosine phosphorylation in the MiaPaCa-2 cell line. Tyrosine kinase inhibitors may prove to be useful agents for the treatment of pancreatic cancer.

Catechols↗

Transforming growth factor alpha is trophic to pancreatic cancer in vivo.

Pancreatic cancer cell lines overexpress epidermal growth factor (EGF) receptors and also have the capacity to produce transforming growth factor alpha (TGF alpha), the alternate agonist of the EGF receptor. The purpose of this study was to determine if TGF alpha had a trophic effect on the growth of pancreatic cancer in vivo. Syrian golden hamsters were inoculated with 50,000 H2T hamster ductal pancreatic cancer cells. The hamsters were then randomised to three equal groups: the groups received either saline (control), EGF, or TGF alpha, each by intraperitoneal injection, three times a day. Treatment continued for seven weeks, and each week the hamsters were weighed and tumour areas were measured. The hamsters were then killed, and the tumours were excised, weighed, and extracted for assay of DNA content as a measure of cellularity. From week four onwards both EGF and TGF alpha significantly stimulated tumour growth. Although tumour weights were not significantly different, tumour DNA content had nearly doubled after exposure to both EGF and TGF alpha. It is concluded that like EGF, TGF alpha can stimulate pancreatic cancer growth in vivo, and this may in part explain the aggressive nature of these cancers in clinical practice.

Animals↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗