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Biomedical subjects

J Scott

Publications and source records attributed to J Scott.

At least 433 records · Page 24Linked to original sources
PubMed1989

Effects of acute ethanol administration on stimulated parotid secretion in the rat.

Young adult male rats previously never exposed to ethanol were given a single dose of 4 ml of 35% (v/v) ethanol in water by direct intragastric intubation (approximate weight related dose = 5.2 g/kg). Control rats were given distilled water in the same volume by the same route or were given no intragastric fluids. After administration of Valium-Hypnorm anesthesia, parotid salivary secretion was stimulated by subcutaneous pilocarpine HCI (10 mg/kg), and accurately timed samples were collected. No differences were recorded in the rate of salivary flow during the initial (5-min) high-flow phase of secretion, but during the subsequent 25-min phase of secretion the output in ethanol-treated rats was depressed by 60% compared to controls (p less than 0.01). Furthermore, electrolyte analyses of this saliva indicated that salivary ductal resorptive activity might be diminished in the presence of high blood ethanol. However, when rats were previously habitually exposed to ethanol at a twice daily dose of 4 ml of 35% (v/v) ethanol in water, the inhibitory action of acute ethanol administration was abolished. Moreover, in these rats there was significantly depressed [Na+] in both high-flow and low-flow saliva samples (p less than 0.01) with little change in [Na+] occurring at higher flow rates. This suggests the possibility of enhanced ductal resorption developing in rats exposed to long-term ethanol feeding.

Alcohol Drinking↗
PubMed1989

The prevalence of oral mucosal lesions in the elderly in a surgical biopsy population: a retrospective analysis of 4042 cases.

A series of over 4000 oral mucosal biopsy cases was examined in two age groups, elderly (greater than or equal to 65 years) and non-elderly, and allocated between seven diagnostic categories. The data were analysed against the know age-sex distribution of the general population of the Mersey Region from which the oral biopsy cases had been drawn. The distribution of diagnostic categories was significantly different between the two age groups. For all diagnostic categories except mucosal cysts (malignant and premalignant disease; benign keratoses; denture-induced hyperplasia; benign proliferative lesions; lichen planus; and miscellaneous diseases) the age-corrected prevalence was higher in elderly than non-elderly with the greatest difference occurring in malignant/premalignant diseases (5.5-fold higher prevalence in the elderly). The results suggested that in the Mersey Regional population the prevalence of oral mucosal disease, of a type and severity to warrant surgical removal of tissue, was 47% higher in the elderly than the non-elderly. These results strongly support the notion that age exerts an important influence on the prevalence and pattern of oral mucosal disease in man.

Aged↗
PubMed1989

Biological and clinical evaluation of the transmandibular implant.

The transmandibular implant has been shown to be a successful clinical solution to prosthetic rehabilitation of patients with gross mandibular atrophy. Aspects of the biocompatibility of the implant material including the component metals in the alloy have been tested in an animal model utilizing sheep. The initial Adelaide results in the clinical multicentre trial are presented. These were generally excellent and the reasons for the few failures are presented.

Aged↗
PubMed1989

RNA editing: a novel mechanism for regulating lipid transport from the intestine.

Human apolipoprotein (apo)-B mRNA undergoes a novel tissue specific editing reaction which replaces a genomically templated cytidine with uridine. This substitution converts codon 2153 from glutamine (CAA) in apo-B100 mRNA to a stop codon (UAA) in apo-B48 mRNA. This novel RNA editing process is responsible for the generation of hepatic apo-B100 and intestinal apo-B48. We have established the following concerning this process: (1) by transfection of a series of deletion mutants into the rat hepatoma cell line McArdle 7777, which makes both apo-B100 and apo-B48, we have defined a minimum sequence of 26 nucleotides that is required for apo-B mRNA editing. The sequence containing the modified nucleotide forms a 26 nucleotide highly conserved stem loop with the modified nucleotide occurring in an 8-base loop. (2) Conversion in vitro of apo-B mRNA has been established, using cell free S100 cytoplasmic extract and synthetic RNA templates. Activity was abolished by protease treatment. (3) Transgenic mice were created which expressed a human apo-B construct spanning the stop codon. Apo-B mRNA was found in all tissues examined and this was shown to undergo editing. (4) In the rat liver, which produces apo B-100 and apo-B48, modulation of the relative proportion of these proteins by thyroxine was demonstrated to be mediated at the level of the RNA editing mechanism. It is concluded that apo-B mRNA is edited by a generally expressed protein and editing is highly regulated.

Animals↗
PubMed1989

Toxoplasmosis in heart and heart and lung transplant recipients.

Of the first 250 heart and 35 heart and lung transplant recipients at Papworth Hospital, Cambridge, who survived for more than one month after transplantation, 217 heart and 33 heart and lung patients were investigated serologically for evidence of Toxoplasma gondii infection. Six patients acquired primary T gondii infection, most probably from the donor organ. Five patients experienced T gondii recrudescence, two of whom had recovered from primary infection a few years earlier. Two patients died from primary T gondii infection and the severity of symptoms in the other patients with primary infection was related to the amount of immunosuppressive treatment. Prophylaxis with pyrimethamine (25 mg a day for six weeks) was introduced for T gondii antibody negative transplant recipients who received a heart from a T gondii antibody positive donor after the first four cases of primary toxoplasmosis. Of the seven patients not given pyrimethamine, four (57%) acquired primary T gondii infection. This compared with two of the 14 patients (14%) given prophylaxis.

Adult↗
PubMed1989

Airway mucosal bioelectric potential difference in cystic fibrosis after lung transplantation.

Bioelectrical potential difference (PD) across the respiratory mucosa is raised in cystic fibrosis (CF). We have recorded airway potentials from seven patients with CF who had undergone heart-lung transplantation and from eight patients without CF who had had transplants for cardiovascular disease; comparison of these populations controls for the effects of denervation and immunosuppressive treatment. Six patients without CF who had not had transplants formed an additional control. PD was recorded during routine fiberoptic bronchoscopy, using a Ringer's-perfused exploring bridge connected across a high impedance amplifier to an intravenous reference bridge. Bronchial lavage and sputum culture revealed no evidence of infection. Bronchial PD was similar in all three groups of patients at equivalent sites. However, nasal PD was raised in the CF group (mean value, 44 mV +/- 3.9 SE) compared with the patients who had transplants for cardiovascular disease (mean, 18 mV +/- 1.1 SE), and the control patients (mean, 15 mV +/- 1.2 SE). We conclude that the epithelial defects that result in raised airway potentials in CF do not recur in the transplanted lung.

Adolescent↗
PubMed1989

The importance of cytomegalovirus in heart-lung transplant recipients.

The first 33 heart-lung transplant recipients in our series were studied for evidence of CMV infection. CMV infection was diagnosed by a change in the serologic status, viral culture, or histology of lung tissue. Of 18 patients who were preoperatively negative for CMV antibody, eight received organs from CMV antibody-positive donors. Five developed pneumonitis (fatal in three)l; one survived primary CMV of the GI tract. Those who recovered from CMV pneumonitis received IV ganciclovir with CMV hyperimmune globulin given prophylactically from the time of transplantation. Only three of ten antibody-negative patients receiving organs from antibody-negative donors developed primary CMV, characterized by only fever in two but associated with rejection, and repeated infection was fatal in a third. CMV reactivation/reinfection occurred in seven of 15 (47 percent) without clinical disease in all but one case. Following heart-lung transplantation, CMV is the cause of considerable mortality and morbidity. We recommend that CMV antibody-negative recipients should receive organs only from antibody-negative donors. If a donor/recipient mismatch occurs, hyperimmune globulin and ganciclovir may improve survival.

Adult↗
PubMed1989

The reducing effects of tazifylline on histamine-induced bronchoconstriction in atopic asthmatics.

Percentage reductions in the peak flow rates to a standardized number of histamine inhalations were compared after 7 days of treatment with 10 mg bd tazifylline and after 7 days of placebo in a randomized crossover study in 11 male seasonal atopic asthmatics. After tazifylline, mean % reductions in peak flow rates were significantly lower than after placebo (p = 0.03). The effects of tazifylline had disappeared within 7 days of stopping treatment. Using a 50% decrease in bronchial reactivity as the criteria of "protection", 7 of the subjects were "protected" by tazifylline only and none by placebo only (p = 0.03).

Adolescent↗
PubMed1989

[Clinical applications of the heart-lung transplant. Clinical results 5 years after the start of the program at Papworth].

In this study is reviewed the experience at Papworth Hospital, Cambridgeshire, and Great Ormond Street Hospital, London, with combined heart-lung transplantation. Between April 1984 and June 1989, 73 patients have undergone heart-lung transplantation. Donors and recipients were carefully matched with regards to serology, morphology and cytomegalovirus compatibility. Heart preservation was based on use of cold St. Thomas' cardioplegic solution; a pulmonary preservation fluid has been developed that allows distant organ procurement with a single pulmonary artery flush technique (Papworth solution). The recipients were: 21 pts with Eisenmenger's syndrome, 15 pts with pulmonary hypertension, 37 pts with pulmonary disease (including 22 cystic fibrosis). The results are: no surgical mortality; no acute cardiac rejection episodes. Twenty-three patients died (16 with infections, 3 with obliterative bronchiolitis, 2 with cerebral embolism and 2 others). The actuarial survival rate at one year is 73.2%; 63% at two years and 47.4% at four years. The use of transbronchial biopsy of the lung has provided accurate early and safe diagnosis of pulmonary rejection. Development in organ preservation and patient management, as well as careful selection of recipients and donors, have led to the effective use of resources and thereby to these good results.

Adolescent↗
PubMed1989

The apolipoprotein B gene is constitutively expressed in HepG2 cells: regulation of secretion by oleic acid, albumin, and insulin, and measurement of the mRNA half-life.

The objective of this study was to establish conditions whereby apoB secreted from HepG2 cells could be regulated over a wide range, and to determine whether changes of output were correlated with the level of apoB mRNA. The presence of oleate (complexed to 3% albumin at a molar ratio of 1.7:1) resulted in a 3.5-fold stimulation of apoB secretion that was apparent after only 3 h. Insulin halved the rate of apoB output and the inhibition was detectable within the physiological insulin range, but was not apparent until 12-16 h. Albumin in the culture medium had a dose-dependent inhibitory effect on apoB production. Overall, apoB secretion from HepG2 cells was modulated over a 7-fold range. However, when apoB mRNA was assayed by slot-blot hybridization, no change was detectable under any of the conditions that modulated apoB output. Quantitative solution hybridization was used to confirm that oleate did not affect the level of apoB mRNA. Kinetic analysis of the decay of [3H]uridine-labeled apoB mRNA showed that the half-life of apoB mRNA was 16 h. We conclude from these studies that the apoB gene is constitutively expressed in HepG2 cells and that the mechanism of acute regulation of apoB production by these cells must involve co- or post-translational processes.

Albumins↗
PubMed1988

Changes in factor VIII proteins after cardiopulmonary bypass in man suggest endothelial damage.

16 patients undergoing coronary artery bypass grafting using cardiopulmonary bypass (CPB) had blood samples taken at various times before, during and up to 1 week after surgery for estimation of beta-thromboglobulin (BTG), alpha-1-antichymotrypsin (ACT), factor VIII procoagulant protein (VIII:C), von Willebrand factor antigen (vWF:Ag) and ristocetin co-factor (vWF:RiCoF). vWF:Ag and vWF:RiCoF rose during and following surgery in a different manner to ACT. At 1 week there was a significantly disproportionate rise in vWF:Ag compared to vWF:RiCoF which suggested a degree of pulmonary endothelial damage. Prostacyclin, which was administered to 8 of the patients during CPB, reduced platelet activation as measured by a reduction in the release of BTG and also attenuated the consumption of VIII:C. It had no effect on pulmonary endothelial damage as measured by the ratio of vWF:Ag to vWF:RiCoF.

Adult↗
PubMed1988

Thyroid hormone modulates the introduction of a stop codon in rat liver apolipoprotein B messenger RNA.

Apolipoprotein B (apoB) biosynthesis by rat liver was studied following thyroid hormone (3,5,3'-triiodo-L-thyronine) administration to hypothyroid rats. Pharmacologic doses of 3,5,3'-triiodo-L-thyronine caused suppression of apoB100 synthesis but did not affect apoB48 levels. There was no detectable apoB100 synthesis in hyperthyroid rats. To examine whether these results were mediated by the previously demonstrated mechanism of RNA modification (Powell, L. M., Wallis, S. C., Pease, R. J., Edwards, Y. H., Knott, T. J., and Scott, J. (1987) Cell 50, 831-840), the DNA sequence corresponding to the C-terminal end of rat apoB48 was determined from rat liver cDNA clones. Rat cDNAs contained a stop codon at an identical position to that found in human and rabbit apoB48 intestinal cDNA. To quantitate the relative amounts of apoB100 and apoB48 message, cDNA was synthesized from hepatic and intestinal apoB RNA and a 207-base pair fragment amplified using the polymerase chain reaction. The products were then differentially hybridized with oligonucleotides specific for apoB100 (containing CAA) or apoB48 (TAA). Control and hypothyroid liver contained approximately equal amounts of CAA and TAA, while hyperthyroid liver contained greater than 90% TAA. All gut samples contained 94-98% TAA. Genomic DNA from rat liver contained only CAA. The results demonstrate that apoB mRNA modification can be hormonally modulated in the adult rat by induction of a mechanism involving substitution of a stop codon into hepatic apoB100 mRNA.

Animals↗
PubMed1988

The effect of East Coast fever immunisation and different acaricidal treatments on the productivity of beef cattle.

A trial was performed on a farm in the Coast Province of Kenya to study the effects of East Coast fever immunisation and different acaricidal treatments on the productivity of immunised and unimmunised beef cattle. Eighty cattle were immunised against Theileria parva parva (Marikebuni) by the infection and treatment method and a similar group was left as an unimmunised control. Immunisation had no deleterious effect on the cattle. After immunisation, the immunised and control groups were each subdivided into four groups of 20 and each subgroup was managed under a different tick control regimen. The tick control regimen were, acaricidal spraying twice a week or once every three weeks, the application of acaricide-impregnated ear-tags, and no tick control. During a nine-month exposure period there were 18 cases of East Coast fever among the 80 immunised cattle, three which were severe and the others mild. Among the 80 unimmunised cattle there were 57 cases of East Coast fever, 50 of which were severe. The highest morbidity and mortality occurred in the groups under limited tick control or without tick control. Overall weight gain in the immunised cattle, irrespective of the tick control regimen, was better than the weight gain in the unimmunised groups. Within the immunised groups, the weight gain of the cattle sprayed twice weekly was comparable to the weight gain of the animals with acaricidal ear-tags and was significantly higher than the weight gains in the groups sprayed once every three weeks or with tick control. Preliminary cost/benefit analysis showed that it was uneconomical to maintain unimmunised cattle under limited or no tick control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Heart-lung transplantation for cystic fibrosis.

13 patients with severe lung disease and cor pulmonale from cystic fibrosis were accepted for heart-lung transplantation (HLT). 6 have had the operation, of whom 5 are well, with normal lung function, 3-29 months after operation. 1 patient died from adult respiratory distress syndrome after reoperation to control persistent chest-wall bleeding: at necropsy, this patient proved to have cirrhosis. Respiratory tract infections and acute lung rejection after HLT for cystic fibrosis were no more common than in other HLT patients. Of the 7 patients for whom suitable donor organs were not found, 3 died within 3 months of assessment. Initial severity of disease had been similar to that in the transplant group. The cost of assessment, operation, and 1 year's treatment after HLT is similar to that of medical treatment for such patients.

Adult↗