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Biomedical subjects

H Thompson

Publications and source records attributed to H Thompson.

At least 55 records · Page 3Linked to original sources
PubMed1998

The immunology of canine leishmaniosis: strong evidence for a developing disease spectrum from asymptomatic dogs.

Asymptomatic mixed breed dogs (49) from a region of high incidence of visceral leishmaniosis in Portugal were examined for the presence of Leishmania-specific cellular immunity using a proliferation assay and humoral immunity using an indirect antibody fluorescent test (IFAT) and an ELISA. The results were compared directly with 25 mixed breed dogs permanently residing in a non-endemic region (Scotland). Unlike similar studies in humans from non-endemic areas, there was no evidence of any immunological response against leishmanial antigen whatsoever from the latter group of animals. Of the 49 dogs from Portugal, however, 20 had demonstrable parasite-specific cellular immunity. Depending on the assay and criteria used to measure a positive humoral response, 11, 16 or 24 dogs had a Leishmania-specific humoral response with the ELISA being the most sensitive assay system. While 16, 12 or 8 of the dogs had clearly only a cellular response (depending on which criterion was used to constitute a true antibody response) and 7, 8 or 12 had only humoral response, other 4, 8 or 12 of the dogs had both cellular and humoral responses. This study clearly demonstrates that the infection rate of canine leishmaniosis is not only higher than previously thought using serological tests alone but that the response to infection is already highly polarised in many asymptomatic dogs. It is postulated that an individual dog's position within the immunological spectrum is likely to indicate how the disease will progress.

Animals↗
PubMed1998

Detection of feline parvovirus in dying pedigree kittens.

Feline parvovirus (FPV) was detected in the intestinal tract contents of 13 pedigree kittens which were fading or died suddenly by the use of a new chromatographic test strip for canine parvovirus (CPV) and FPV. The test appeared to be sensitive and specific for the detection of FPV and was a useful diagnostic aid. In three cases in which virus was grown in cell culture, the isolates were characteristic of FPV and not CPV. Cats in the households in which the kittens were reared were regularly immunised with FPV vaccines. The most likely explanation for the occurrence of FPV-associated disease was exposure of the young kittens to large doses of virus contaminating the environment.

Animals↗
PubMed1998

Two malate dehydrogenases in Methanobacterium thermoautotrophicum.

Methanobacterium thermoautotrophicum (strain Marburg) was found to contain two malate dehydrogenases, which were partially purified and characterized. One was specific for NAD+ and catalyzed the dehydrogenation of malate at approximately one-third of the rate of oxalacetate reduction, and the other could equally well use NAD+ and NADP+ as coenzyme and catalyzed essentially only the reduction of oxalacetate. Via the N-terminal amino acid sequences, the encoding genes were identified in the genome of M. thermoautotrophicum (strain DeltaH). Comparison of the deduced amino acid sequences revealed that the two malate dehydrogenases are phylogenetically only distantly related. The NAD+-specific malate dehydrogenase showed high sequence similarity to L-malate dehydrogenase from Methanothermus fervidus, and the NAD(P)+-using malate dehyrogenase showed high sequence similarity to L-lactate dehydrogenase from Thermotoga maritima and L-malate dehydrogenase from Bacillus subtilis. A function of the two malate dehydrogenases in NADPH:NAD+ transhydrogenation is discussed.

Acetates↗
PubMed1998

GDNF deficit in Hirschsprung's disease.

BACKGROUND/PURPOSE: In 1996, the glial cell line-derived neurotrophic factor (GDNF) was identified as one of the ligands of the RET transmembrane receptor. In the same year, GDNF mutations were found in association with RET protooncogene mutations in Hirschsprung patients. Mutations in GDNF per se are thought neither necessary nor sufficient to cause Hirschsprung's disease (HD). To date, our study group has identified GDNF mutations only in 2 of 98 cases of intestinal dysganglionosis. The aim of our study was to investigate a possible expression deficit of GDNF in the enteric nervous system of Hirschsprung patients not mutated for the GDNF gene. METHODS: We used rabbit polyclonal antibodies raised against a peptide corresponding to amino acids 186-205 mapping within the carboxy-terminal domain of human GDNF. GDNF expression was studied immunohistochemically in surgical specimens from 30 HD cases (27 classic forms and 3 ultralong forms) and from 10 age-matched controls. Serial sections from the same full-thickness specimens were investigated with the following histochemical and immunohistochemical techniques: acetylcholinesterase, lactate dehydrogenase, succinic dehydrogenase, alpha-naphthyl-esterase, glial fibrillary acid protein, S-100 protein, and neuron-specific enolase. RESULTS: A high level of GDNF expression was found in normal intestine and in Hirschsprung ganglionic segment. Satellite elements of myenteric ganglia presented a strong immunoreactivity to GDNF. Conversely, the aganglionic segment showed cholinergic hyperinnervation and hypertrophic trunks of nerve fibers in the muscular interstitium with complete absence of GDNF expression. The small ganglia of the hypoganglionic segment showed a reduced GDNF immunoreactivity. CONCLUSIONS: GDNF, a distantly related member of the transforming growth factor-beta superfamily, is a potent neurotrophic and survival factor for neurons and enteric ganglion cells. Mutations of the GDNF gene or GDNF expression deficit interrupt the faithful GDNF signaling via Ret, contributing to HD pathogenesis.

Animals↗
PubMed1998

Occupancy of a teaching hospital adult intensive care unit by high dependency patients.

We assessed the hourly occupancy of our intensive care unit by high dependency patients over an 8-week period using the criteria established by the Working Group on Guidelines on Admission to and Discharge from Intensive Care and High Dependency Units published by the National Health Service Executive. High dependency patients accounted for 1914 bed hours (21.6%) out of a potential available total of 8880 hours. Measurement of Therapeutic Intervention Scoring System points and Acute Physiology and Chronic Health Evaluation II scores confirmed that categorising patients according to the new guidelines produced significantly different populations of patients. Mean (standard deviation) Therapeutic Intervention Scoring System points for intensive care status patients were 38.57 (10.40) compared to 21.65 (5.98) points for high dependency status patients (p < 0.001). Median (range) Acute Physiology and Chronic Health Evaluation II score for intensive care status patients was 16 (1-45) compared to 11 (1-27) for high dependency status patients (p < 0.0001). Calculating bed occupancy with different definitions for the whole of our intensive care unit population during the 8 weeks revealed a range of occupancies between 85.3% and 107.3%. We recommend the intensive care unit bed occupancy should be calculated in a standard manner nationally to allow comparison between units. We suggest that hourly occupancy be adopted as the universal method.

APACHE↗
PubMed1998

Evaluation of a training package in the assessment and management of depression in primary care.

This study aimed to evaluate the impact on the behaviour and attitudes of experienced general practitioners of a 10-hour training package in the assessment and management of depression. Twenty general practitioners participated. Both subjective and objective assessments were carried out which suggested significant improvements in both assessment and management skills. However, subjectively reported changes were not always supported by the objective data obtained from rating role-played interviews. The role-played patients rated the doctors as better communicators after training. All participants felt attending the course was beneficial. They all felt more confident in their abilities to deal with depression and said the skills they had learnt on the course would be useful to them in their future work. An outcome study is now underway in order to assess whether the training package, which has been demonstrated to have an impact on the behaviour, skills and attitudes of doctors, has an impact on the health of patients.

Adult↗
PubMed1998

Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced mouse lung tumor formation by FGN-1 (sulindac sulfone).

The sulfone derivative of the non-steroidal anti-inflammatory drug (NSAID), sulindac, has been reported to inhibit mammary and colon tumor formation in rodent models of chemically-induced carcinogenesis. Unlike its parent compound, this metabolite lacks cyclo-oxygenase inhibitory activity. A tumor induction protocol, consisting of NNK administration in the drinking water over several weeks to model chronic human exposure, was used to test whether the sulfone (called FGN-1) could inhibit the formation of primary lung tumors in mice. A total of 150 female, AIN76A-fed, A/J mice received 9 mg of NNK each. Concentrations of FGN-1 that had been previously determined not to affect body weight gain were added to the food at levels of 0, 250, 500 and 750 mg/kg of diet (30 mice/group) starting 2 weeks before NNK administration and continuing for 22 weeks. At that time pleural surface tumors were counted. Tumor incidence decreased significantly from 96 % in the control diet and 93% in the 250 FGN-1 mg/kg diet to 63 and 67% in the 500 and 750 mg FGN-1/kg diet groups, respectively (P < 0.001 by chi-square analysis). Lung tumor multiplicity decreased from 18.1+/-3 tumors/ mouse (mean+/-SEM, control diet) to 12.3+/-3 (250), 5.3+/-1 (500) and 2.1+/-1 (750) (P < 0.0005 by post hoc ANOVA). In previous studies using this carcinogenesis protocol, the maximum tolerated dose of sulindac inhibited lung tumor multiplicity by no more than 50% with no effect on incidence. This dose-dependent reduction in tumorigenesis by a non-toxic dose of FGN-1 indicates a strong chemopreventive activity against experimental induction of lung carcinogenesis. The greater potency of the sulfone over sulindac and its lack of toxic side effects because of its inability to affect cyclo-oxygenase activity suggests that clinical testing in individuals at high risk for lung cancer should be considered.

Animals↗
PubMed1998

Cost-effectiveness of a new treatment for somatized mental disorder taught to GPs.

BACKGROUND: Patients with mental disorder presenting with medically unexplained symptoms (somatized mental disorder) are difficult to treat and consume a lot of health care. OBJECTIVES: The aim of the study was to examine the cost-effectiveness of a training package for somatized mental disorder delivered by GPs. METHODS: The study design was a prospective, before- and after-training study of different cohorts of patients attending eight GPs, acting as their own controls. Cost-effectiveness analysis was estimated using changes in case level on a self-rated psychiatric symptom questionnaire (GHQ-12) and direct health costs between the index consultation and 3 months later. RESULTS: There were 103 and 112 patients with somatized mental disorder in the before and after training cohorts, respectively. After training, costs of referrals outside the primary care team decreased significantly by 23%, with little overall change in primary care costs. Total direct health care costs, including training, were reduced by 15%. After training, an extra 17 patients were successfully treated (no longer GHQ-12 cases) at 3 months. The marginal cost-effectiveness per extra successfully treated patient was pound sterling 325 and the cost per successfully treated case was 69% of the cost of the GP's usual treatment. CONCLUSIONS: Training GPs with the reattribution training package appears to be extremely cost-effective.

Cost-Benefit Analysis↗
PubMed1998

Investigation of osteochondrosis in grazing beef cattle.

Severe lameness attributed to osteochondrosis is described in an extensively managed Brahman herd grazing on improved native pasture. Clinical signs were observed in five animals, three of which were necropsied. The most prominent lesions were in the elbow and stifle joints. There were multiple fissuring and ulceration of thickened articular cartilage with numerous osteochondral bodies present in the joint spaces. All affected animals were entire males sharing a common ancestral sire. Inheritance and gender were suspected to be contributing factors in the development of the disease.

Animals↗
PubMed1997

Morphological and biochemical status of the mammary gland as influenced by conjugated linoleic acid: implication for a reduction in mammary cancer risk.

Previous research showed that treatment with conjugated linoleic acid (CLA) during the period of active mammary gland morphogenesis was sufficient to confer a lasting protection against subsequent mammary tumorigenesis induced by methylnitrosourea. The present study was designed to characterize certain morphological and biochemical changes of the mammary gland that might potentially render it less susceptible to cancer induction. Female Sprague Dawley rats were fed a 1% CLA diet from weaning until about 50 days of age. The mammary gland parameters under investigation included (a) the deposition of neutral lipid, (b) the identification and quantification of CLA and its metabolites, (c) the density of the epithelium, and (d) the proliferative activity of various structural components. Our results showed that CLA treatment did not affect total fat deposition in the mammary tissue nor the extent of epithelial invasion into the surrounding fat pad but was able to cause a 20% reduction in the density of the ductal-lobular tree as determined by digitized image analysis of the whole mounts. This was accompanied by a suppression of bromodeoxyuridine labeling in the terminal end buds and lobuloalveolar buds. The recovery of desaturation and elongation products of CLA in the mammary gland confirmed our prior suggestion that the metabolism of CLA might be critical to risk modulation. The significance of the above findings was investigated in a mammary carcinogenesis bioassay with the use of the dimethylbenz[a]anthracene model. When CLA was started at weaning and continued for 6 months until the end of the experiment, this schedule of supplementation produced essentially the same magnitude of mammary tumor inhibition in the dimethylbenz[a]anthracene model as that produced by 1 month of CLA feeding from weaning. The observation is consistent with the hypothesis that exposure to CLA during the time of mammary gland maturation may modify the developmental potential of a subset of target cells that are normally susceptible to carcinogen-induced transformation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

The formation of transferrin receptor-positive sickle reticulocytes with intermediate density is not determined by fetal hemoglobin content.

Erythrocyte dehydration is an important feature of sickle cell disease, leading to increased sickle hemoglobin polymerization and decreased red blood cell survival. Substantial in vivo dehydration appears to occur in reticulocytes or in an even younger subset of reticulocytes that are positive for transferrin receptor. Previous studies have suggested both sickling-dependent and sickling-independent components of dehydration for these cells. Two types of investigations are reported here. The first series of experiments explored the possibility that fetal hemoglobin (HbF) content influences the in vivo dehydration of very young, transferrin receptor-positive (T+) cells. These studies confirmed that in most patients the T+ cells in the densest fraction lacked HbF (T+ F-). However, T+ F- and T+ F+ cells appeared to have the same tendency to become moderately dense. The second type of investigation examined moderately dense T+ cells with normalized K+ content and determined the effect of HbF content on KCl cotransport-mediated dehydration in oxygenated incubations. Under these conditions, both T+ F- and T+ F+ cells had an equal tendency to become more dense by this pathway. Taken together, these studies indicate that at least some young sickle cells become moderately dense due to higher KCl cotransport activity independent of HbF content (and by inference, independent of sickling). However, to become very dense, it appears that further dehydration through a sickling-mediated pathway is required. We suggest that the dehydration of young sickle cells occurs in two steps, with the first dominated by KCl cotransport and the second having an important sickling-dependent component.

Anemia, Sickle Cell↗
PubMed1997

Caloric intake and weight gain of rats depends on endogenous fat preference.

Within outbred colonies, subpopulations of rats exist that exhibit inherent preferences for one type of macronutrient over another (e.g., fat vs. carbohydrate). Prior investigations into the effect of dietary manipulations on consumption or weight gain have not taken into account endogenous macronutrient preferences. The purpose of this study was to examine whether inherent fat preferences translate into differences in caloric consumption and weight gain in rats when fed high-fat and high-carbohydrate diets. Rats that exhibited a preference for fat were identified using a previously described paradigm and were subsequently placed on either a high-fat or high-carbohydrate diet. Daily caloric intakes and weekly weights were monitored over a 28-day period and compared with data for animals with a low-fat preference on the same diets. By the conclusion of the study, the low-fat-preferring rats on the high-carbohydrate diet had consumed significantly more calories than the high-fat-preferrers maintained on the same diet. In contrast, the amounts of calories consumed on the high-fat diet were not significantly different between the low- and high-fat-preferring animals. Those animals with a preference for fat placed on a high-carbohydrate diet weighed significantly less by the end of study, even though they consumed the same number of calories as animals on the high-fat diet. We conclude that the outcome of nutritional studies designed to examine caloric intake and weight gain can be influenced by the innate macronutrient preference of the animal.

Animals↗
PubMed1997

The management of giant retinal tears using perfluoroperhydrophenanthrene. A multicenter case series. Vitreon Collaborative Study Group.

OBJECTIVE: The purpose of the study was to determine the predictors of success and evaluate the use of perfluoroperhydrophenanthrene as an intraoperative and postoperative tool in the management of giant retinal tears in a multicentered collaborative study. DESIGN: Multicentered prospective case series. PARTICIPANTS: Twenty-three centers consecutively enrolled 162 eyes of 161 patients with retinal tears 90 degrees or greater in circumferential extent. INTERVENTION: Perfluoroperhydrophenanthrene was used as an intraoperative surgical adjunct in all cases and left after surgery in 16 eyes (9.9%). MAIN OUTCOME MEASURES: Retinal reattachment and visual acuity. RESULTS: Intraoperative reattachment was achieved in 158 eyes (97.5%); 147 eyes (90.7%) remained attached at their most recent follow-up. Seventy-nine eyes (48.8%) experienced an improvement in their visual acuity, 26 eyes (16.0%) remained unchanged, and 57 (35.2%) worsened. Recurrent retinal detachment occurred in 80 patients (49.4%). Other significant postoperative complications included cataract formation in 20 (39.2%) of 51 eyes, macular pucker in 12 (7.4%), corneal decompensation in 10 (6.2%), and hypotony (intraocular pressure equal to or less than 5 mmHg) in 9 (5.6%). A chi-square analysis of preoperative characteristics showed that hypotony (P = 0.007), macular detachment (P = 0.020), a history of cataract extraction (P = 0.003), poor visual acuity (P = 0.000), giant tear extent greater than 180 degrees (P = 0.004), and higher grade proliferative vitreoretinopathy (P = 0.000) all predicted a poor visual outcome. Vitreon (Vitrophage, Inc., Lyons, IL) was left in 16 eyes (9.9%) for an extended postoperative retinal tamponade for between 3 and 1034 days (mean, 87.2 days). The Vitreon was well tolerated, and these eyes experienced a similar outcome and rate of retinal reattachment to the rest of the group. CONCLUSIONS: Vitreon is a safe and useful adjunct to pars plana vitrectomy in the management of giant retinal tears and may, additionally, be the perfluorocarbon liquid that can be used most safely as a temporary postoperative tool for extended retinal tamponade, reinforcing its role as a useful adjunct in the management of these complex retinal detachments.

Adolescent↗
PubMed1997

Multiple repetitive DNA sequences in the paracentromeric regions of Arabidopsis thaliana L.

Nine repetitive DNA sequences, present in the haploid Arabidopsis thaliana genome in 7-300 copies, were hybridized in situ to metaphase and interphase chromosomes. Every sequence was detected on all five chromosome pairs, but was not evenly dispersed over the genome. Clusters of signals were found in particular regions of the centromeric heterochromatin, and each sequence showed a characteristic distribution pattern. Some sequences hybridized more strongly on different chromosomes, reflecting chromosome-specific amplification or the presence of homologous sequences. No hybridization signals could be detected on euchromatic regions. In situ hybridization on extended chromatin fibres showed that the pAL1 repeats are interrupted by another repetitive DNA sequence. A cosmid subclone (74A) contained a (GA)38 microsatellite motif, and hybridization with a (GA) oligonucleotide revealed that most of the hybridization sites of 74A correspond to the distribution of this microsatellite motif. The results show that the paracentromeric heterochromatin of A. thaliana chromosomes is composed not only of the tandemly arranged 180-bp repeat family pAL1/pAtMr, but also of some other repetitive sequences, thus giving a better understanding of the organization of sequences at the centromeres of A. thaliana.

Arabidopsis↗
PubMed1997

Immortalized mouse mammary cells in vivo do not exhibit increased telomerase activity.

The acquisition of immortalization is an early and carefully documented event in mouse mammary tumorigenesis. Activation of telomerase activity is one hypothesis to explain the acquisition of immortalization. We examined the activity of telomerase in well-defined immortalized, non-tumor cell populations of mouse mammary tissue in vivo. The results indicated that normal virgin and mid-pregnant mammary gland had low to moderate levels of telomerase activity, respectively. In comparison with the levels detected in pregnant mammary gland, telomerase activity was elevated in mammary tumors in situ and in established mammary cell lines in vitro, both tumorigenic and nontumorigenic; however, hyperplastic alveolar preneoplastic mammary outgrowths and non-tumorigenic ductal outgrowths, both in vivo immortalized populations, had telomerase activity <12% of the levels detected in normal pregnant mammary gland. These results suggest that elevated telomerase activity is not necessary for the immortalization phenotype in in vivo mouse mammary cell populations and that elevated telomerase activity occurs as a late event in mammary tumorigenesis. Furthermore, the data suggest that low levels of telomerase activity are characteristic for mouse mammary epithelial cells and not sufficient for immortalization. These data suggest that other factors play more important roles in the induction and/or maintenance of the immortalization state in mammary cell populations.

Animals↗
PubMed1996

Dehydration of transferrin receptor-positive sickle reticulocytes during continuous or cyclic deoxygenation: role of KCl cotransport and extracellular calcium.

The K+ efflux that mediates sickle-cell dehydration may occur through several pathways, including two with a high capacity for mediating rapid K+ loss, KCl cotransport and the Ca(2+)-dependent K+ channel [K(Ca2+)]. The rate and pathway of red blood cell (RBC) dehydration most likely depends on cell age and hemoglobin (Hb) composition, with the presence of HbF playing an important role. Oxygenated sickle RBCs have relatively stable cell volume during incubation in vitro, whereas deoxygenated cells become dehydrated, and therefore more dense, due to activation of one or more K+ efflux pathways. In this investigation, sickle RBCs were deoxygenated either continuously or in 15-minute cycles for 4 hours, and the density increases of very young, transferrin receptor-positive (TfR+) cells and the remaining TfR- cells were determined. The contribution of KCl cotransport was estimated by replacing Cl- with NO3-. K(Ca2+) was inhibited by removal of Ca2+ or addition of charybdotoxin (ChTX). For both continuous and cyclic deoxygenation, TfR+ cells had a greater density increase when compared with TfR- cells. The lower percentage of HbF found in the TfR+ population may contribute to this difference. With continuous deoxygenation, the density shift was decreased by inhibition of K(Ca2+), but not by inhibition of KCl cotransport. With cyclic deoxygenation, the density shift was decreased in an independent, additive manner by inhibition of both pathways. Thus, cyclic deoxygenation of sickle cells under these conditions appears to activate both K(Ca2+) and the KCl cotransporter.

Body Water↗
PubMed1996

A novel repetitive sequence associated with the centromeric regions of Arabidopsis thaliana chromosomes.

The middle repetitive fraction of the Arabidopsis genome has been relatively poorly characterized. We describe here a novel repetitive sequence cloned in the plasmid mi167, and present in approximately 90 copies in the genome of Arabidopsis thaliana ecotype Columbia. Hybridization analysis to physically mapped YAC clones representing Arabidopsis chromosome 4 revealed four mi167-hybridizing loci, all clustered near the centromere. No other loci were detected on YAC clones covering chromosome 4. In situ hybridisation experiments to Arabidopsis chromosome spreads showed that mi167-hybridizing sequences are clustered at the centromeric heterochromatin of all five chromosomes; on two chromosomes the hybridization appeared to be localised on one arm. Additional mi167-hybridizing loci were detected, one of which was adjacent to a non-centromeric, heterochromatic region. This work supports the idea that the majority of middle repetitive DNA in the Arabidopsis genome is clustered. It also adds to our understanding of the organization of the centromere of Arabidopsis chromosome 4.

Arabidopsis↗