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Biomedical subjects

M Thomson

Publications and source records attributed to M Thomson.

At least 73 records · Page 4Linked to original sources

Molecular and cellular mechanisms used in the acute phase of stimulated steroidogenesis.

Steroidogenic tissue can respond almost immediately to a stimulatory hormonal stimuli. Recent findings are shedding light on the molecular and cellular mechanisms that are used to synthesize and export steroid hormones in the acute phase of stimulation. In addition to utilising the cAMP intracellular messenger system to convey a stimulatory message, steroidogenic cells may employ the protein kinase C, arachidonic acid, tyrosine phosphate and nitrous oxide systems. It has been proposed that cholesterol laden vesicles travel along a network of intermediate filaments to reach the mitochondria. Cholesterol may then translocate from the outer mitochondrial membrane to the inner via sites of contact between the two membranes. These contact sites may be composed of protein bridges which include the constituents, porin, the benzodiazepine receptor and GTP binding proteins. Cholesterol is transported through the contact sites to the inner membrane and on reaching cytochrome P450 side chain cleavage (P450scc), cholesterol is converted to pregnenolone. Pregnenolone is in turn converted to a range of steroid hormones via enzyme casades. GTP binding proteins may regulate the contact site between the inner and outer membranes and thereby modulate cholesterol flux to P450scc. In the adrenal and gonads the rate that cholesterol traverses the contact point to reach the inner membrane is accelerated by the steroidogenic acute regulatory protein. Newly synthesized steroid hormones are transported to the cell periphery for export via a mechanism that may utilise an ion exchange protein.

Adrenal Glands↗

Dust control for material handling operations: a systematic approach.

Material handling operations are used widely in industry. Often they produce unacceptable levels of dust. This article proposes a systematic approach to dust control for material handling operations. It focuses on the appropriate dust control technologies for the wide range of material handling operations. Both dust collection and dust suppression systems are considered. Comparisons are made between competing technologies using available information. Relevant literature resources are compiled and synthesized to provide the reader with the most recent design and operational information. Important areas requiring further research and development work are identified.

Air Pollution↗

A randomised comparison of strategies for reducing infective complications of induced abortion.

OBJECTIVES: To determine lower genital tract carriage rates of C. trachomatis, N. gonorrhoeae and bacterial vaginosis among women seeking termination of pregnancy. To compare two clinical management strategies for minimising the risks of infective morbidity after induced abortion. DESIGN: Prevalence of infections was assessed by screening women undergoing abortion. Clinical management strategies were compared by a randomised trial. SETTING: The gynaecology departments of four hospitals in Scotland. PARTICIPANTS: 1672 women undergoing induced abortion. INTERVENTIONS: Women randomised to prophylaxis received metronidazole 1 g rectally before abortion plus doxycycline 100 mg twice daily for seven days. Women randomised to screen-and-treat received appropriate antibiotics only if screening proved positive for one or more infection. MAIN OUTCOME MEASURES: Prevalences of infections; morbidity in the eight weeks following abortion as assessed by reported symptoms, general practitioner consultation and prescription rates and hospital re-attendances; costs to the NHS of alternative managements. RESULTS: Prevalence rates: C. trachomatis 5.6%; N gonorrhoeae 0.19%; bacterial vaginosis 17.5%. Overall, women allocated to receive prophylaxis had lower rates of measures of short term infective morbidity than those allocated to screen-and-treat. These differences only reached statistical significance for women who were reported negative on screening. The direct costs to the NHS of prophylaxis and screen-and-treat were calculated to be 8.17 and 18.34 per woman, respectively. CONCLUSIONS: Prevalences of lower genital tract infections which have been implicated in increased rates of infective morbidity after abortion are similar to those reported elsewhere. Universal antibiotic prophylaxis is at least as effective as a policy of screen-and-treat in minimising the risk of short term infective morbidity and is far more cost efficient.

Abortion, Induced↗

Deletion analysis of a defective interfering Semliki Forest virus RNA genome defines a region in the nsP2 sequence that is required for efficient packaging of the genome into virus particles.

The 1,244-nucleotide genome of Semliki Forest virus (SFV) defective interfering (DI) RNA 19 (DI-19) is coterminal with the infectious genome and contains two major deletions. One deletion removes the end of the nsP1 gene and the beginning of the nsP2 gene, and the other removes the end of the nsP2 gene, the nsP3 and nsP4 genes, and all of the structural protein genes (M. Thomson and N. J. Dimmock, Virology 199:354-365, 1994). Like all DI SFV RNAs, DI-19 contains three regions that are conserved. Region a comprises the 5' terminus continuous with part of the nsP1 gene, region b comprises a central part of the nsP2 gene, and region c comprises the 3' terminus and the associated untranslated region. A deletion analysis of the 265-nucleotide b region (nucleotides 679 to 943, inclusive) was undertaken to determine its role in genome replication and packaging into DI virus particles. Deleted plasmids were constructed and transcribed, and the resulting DI RNAs were transfected into SFV-infected BHK cells. Putative progeny DI virus particles that had been released into the tissue culture fluid were then serially passaged in new monolayers together with added high-multiplicity SFV, and cells and tissue culture fluids were tested for the presence of DI RNA by reverse transcription-PCR. DI RNA that had all of the b region deleted was replicated well in BHK-21 cells, as shown by the presence of large amounts of negative-sense DI RNA and an increase in the amount of positive-sense RNA in the cytoplasm, but was packaged very inefficiently, as indicated by very low amounts of DI RNA in the tissue culture fluid. The genome of a deletion mutant that retained the 3' 224 nucleotides of region b was packaged successfully, but one that retained only the 5' 41 nucleotides was not detected in the tissue culture fluid. These and other data suggest that nucleotides 720 to 777 of region b are of particular importance in the packaging process. This finding agrees with data obtained with Ross River virus and contrasts with the well-studied Sindbis alphavirus major packaging signal that is located within the nsP1 gene.

Animals↗

Does the CRH binding protein shield the anterior pituitary from placental CRH?

Corticotropin releasing factor (CRH) is released from the hypothalamus and travels to the anterior pituitary where it stimulates the release of adrenocorticotropin (ACTH). In turn, ACTH travels through the blood and stimulates the release of cortisol from the adrenal. The placenta is also a source of CRH and is responsible for the dramatic rises in CRH plasma levels in the third trimester of pregnancy. A CRH binding protein may stop placental CRH from overstimulating the pituitary and may contribute to the reason that pregnant women show only mildly elevated levels of ACTH in the blood. There is evidence to suggest, however, that the CRH binding protein does not completely shield the corticotrope from placental CRH.

Animals↗

Evaluation of mixtures of wild-type HIV-1 and HIV-1 with resistance point mutations against reverse transcriptase inhibitors.

The presence of resistance-related mutations in 185 serial proviral DNA samples from 108 HIV-infected patients was monitored using the line probe assay (LiPA). The proportions of wild-type and mutant virus in each sample were determined. Subsequent samples from the same patient were analysed. Resistance mutations were detected in 58 of 108 patients studied (53.7%), 53 of 73 (72.6%) treated with antivirals and 5 of 35 (14.2%) untreated. The mutations were against zidovudine (51), lamivudine (1), zidovudine and lamivudine (4), zidovudine and zalcitabine (1) and zidovudine and didanosine (1). Among the 58 patients with resistant virus, 168 related mutations were observed: 161 to zidovudine (90 in codon 70, 25 in codon 41 and 46 in codon 215), 5 to lamivudine (codon 184), 1 to zalcitabine (codon 69) and 1 to didanosine (codon 74). Mixtures of wild-type and resistant mutants were detected in 76 of 90 (84.4%) mutated at codon 70, 28 of 46 (60.8%) mutated at codon 215 and in 21 of 25 (84%) mutated at codon 41. The mutations at codon 184 were mixtures of wild-type and resistant in 4 of 5 samples. The agreement between LiPA and sequencing was 96.5%. LiPA was more sensitive for the detection of mutants that were present at low frequency. The analysis of sequential samples from the same patient allowed evaluation of the dynamics of appearance of the resistant mutants.

Anti-HIV Agents↗

Streamwater nitrate concentrations in six agricultural catchments in Scotland.

The concentrations of nitrate-N (NO3-N) in catchment inputs and outputs have been compared and contrasted between 6 farm catchments in Scotland, 3 in the West and 3 in the North-East. Forms of intensive animal farming ranging between beef and dairy cattle, sheep and poultry give different sources for potential NO3-N leakage from the systems. While stream reaches bordered by intensive cereal production give rise to the largest inputs to surface waters, climatic influences result in the more-efficient use of fertilizer- and farm waste-N in the West, and an enhanced potential for N-loss to waters in the cooler North-East, regardless of the N-inputs being considerably lower in the latter region. Although the EC Nitrate Directive limit of 11.3 mg NO3-N 1(-1) was not exceeded, peak values occurring during summer baseflows and autumn soil rewetting were commonly larger than the 'target' maximum concentration of 5.65 mg NO3-N 1-1.

Agriculture↗

Multiple vasoactive factors in epidermal secretions of the Arabian Gulf catfish, Arius bilineatus (Valenciennes).

1. The Arabian Gulf catfish produces proteinaceous epidermal secretions when threatened or injured. 2. The soluble fraction of the catfish epidermal secretions (SES) has vasoconstrictor activities on sheep renal arteries, which can be inhibited by several antagonists, including atropine, indomethacin, prazosin, and verapamil. 3. Mepyramine, yohimbine, and ketanserin have negligible effects on SES-induced contraction. 4. SES exhibits a significant tachyphylaxis upon addition of a second (8.4% reduction) and third (47% reduction) dose of SES to the organ bath, which can be partially prevented by addition of a fresh arterial section prior to each addition. 5. A vasoconstricting activity has been partially purified from SES by gel filtration on Fractogel HW-65(F) and appears to be a protein with a pI near 7.3. This activity is affected only by verapamil and prazosin.

Animals↗

Disorders of the oesophagus and stomach in infants.

Pathological processes and disease entities in the upper gastrointestinal (GI) tract, specifically those of the oesophagus and the stomach in infancy, have received a disproportionately small amount of attention until recently when appreciation of their pathophysiology and concordant importance in terms of symptomatology has been highlighted. This is probably a phenomenon secondary to improved diagnostic yield from the recent technical advances in areas such as infant endoscopy and a shift in opinion regarding the pathophysiological origin of ubiquitous symptoms of infancy such as feeding disorders, colic and irritability. In addition, the apparently complex interactions of various aetiological factors such as pH-independent gastro-oesophageal reflux (GOR), cow's milk protein intolerance (CMPI), Helicobacter pylori gastritis and upper GI motor disorders have in the past 1-2 years become underlined in terms of aetiopathogenesis and have radically changed thinking regarding diagnosis and therapy of infants with apparent upper-GI-associated symptoms. The contribution to comprehension of infant upper GI disorders of inflammatory paradigms and ontogeny of the upper GI tract is also a recent area worthy of mention. The recent advances in all of these areas and their contribution to the understanding, and subsequent diagnosis and therapy, of upper GI symptoms and their explanation by way of aetiopathogenesis will be explored in this chapter.

Child↗

Geographical perspectives on bednet use and malaria transmission in The Gambia, West Africa.

Insecticide-impregnated bednets are now widely accepted as an important tool in reducing malaria-related deaths in children in Africa. Defining the circumstances in which net treatment programmes are likely to be effective is essential to a rational development of this control strategy. In The Gambia a National Impregnated Bednet Programme was introduced into the primary health care system in 1992. Prior to its introduction baseline epidemiological and entomological studies were conducted throughout the country. These studies showed that in areas where mosquito biting nuisance was high, people protected themselves with bednets and that where mosquito densities (and therefore bednet usage) was low malaria prevalence rates were relatively high. Since the national programme is designed to assist only those people who already own a bednet (by providing the insecticide) an understanding of the factors which determine bednet ownership is needed to help evaluate the programme's effectiveness and provide guidelines for increasing bednet usage. Village scale bednet usage rates and malaria prevalence rates obtained from the baseline survey were correlated with certain geographical variables: dominant ethnic group, area, habitat, distance from the River Gambia and distance from the 'bluffline' (the interface between the sandstone soils and alluvial soils which border the river system). In a multiple regression analysis, bednet usage was independently associated with area (P < 0.001), ethnic group (P = 0.010), habitat (P = 0.006) and distance from the river (P = 0.013). A negative association of bednet usage with malaria prevalence persisted after allowing for the other variables. Malaria prevalence was not independently associated with area, ethnic group, habitat or distance from the river. Our analysis showed that the impregnated bednet programme is likely to be most effective in villages which are sited near to or on the alluvial soils in the middle and lower river zones. These villages, which were originally settled for easy access to the river (for transport) and its swampy margins (for rice production) are within the flight distance of mosquitoes that have their breeding sites on the poorly drained alluvial soils. Variation in malaria prevalence rates (after bednet usage has been taken into account) may be related to factors such as poverty and access to health care, and/or to localized differences in the ecology of The Gambia, which determine the duration and intensity of transmission. If the National Bednet Programme is to be effective throughout The Gambia it is vital to develop promotional activities which will encourage bednet usage in areas where nuisance biting by mosquitoes is low.

Animals↗

Histopathological effects of garlic on liver and lung of rats.

The comparative toxic effects of oral and intraperitoneal administration of garlic extracts on lung and liver tissue of rats were studied. Administration of low doses of garlic (50 mg/kg) to rats either orally or intraperitoneally had little effect on lung and liver tissues as compared to control animals. In contrast, administration of high doses of garlic (500 mg/kg) resulted in profound changes in lung and liver tissues of rats. Intraperitoneal administration of the high dose of garlic was more damaging to lung and liver tissue of rats than oral administration.

Administration, Oral↗

An evaluation of garlic and onion as antithrombotic agents.

Garlic (Allium sativum) and onion (Allium cepa) have been evaluated as possible antithrombotic agents. Rats were given aqueous extracts of garlic and onion, orally or intraperitoneally, daily for a period of 4 weeks after which the rats were sacrificed. The blood was collected from the heart without anticoagulant and the serum was prepared. The level of thromboxane B2 (TXB2) in the serum was measured by radioimmunoassay. TXB2 levels in serum of rats treated with the low dose of aqueous extract of garlic (50 mg/kg) was significantly inhibited regardless of the mode of administration (orally or intraperitoneally). At the high dose of garlic and onion (500 mg/kg), a further decrease of TXB2 levels in the serum of the rats was observed. Boiled garlic and onion at high concentration (500 mg/ kg) had very little effect on TXB2 synthesis. This shows that garlic and onion should be consumed in a raw rather than cooked form in order to achieve a beneficial effect. Boiling of these plants may cause the decomposition of the potential antithrombotic ingredient present in these herbs. Garlic was found to be more potent than onion in lowering the TXB2 levels. A high dose of garlic and onion produces toxicity in the rats (unpublished observation). These results show that garlic and onion can be taken frequently in low doses without any side effects, and can still produce a significant antithrombotic effect.

Allium↗

A locus for bipolar affective disorder on chromosome 4p.

The main clinical feature of bipolar affective disorder is a change of mood to depression or elation. Unipolar disorder, also termed major depressive disorder, describes the occurrence of depression alone without episodes of elevated mood. Little is understood about the underlying causes of these common and severe illnesses which have estimated lifetime prevalences in the region of 0.8% for bipolar and 6% for unipolar disorder. Strong support for a genetic aetiology is found in the familial nature of the condition, the increased concordance of monozygotic over dizygotic twins and adoption studies showing increased rates of illness in children of affected parents. However, linkage studies have met with mixed success. An initial report of linkage on the short arm of chromosome 11 (ref. 4) was revised and remains unreplicated. Reports proposing cosegregation of genes found on the X chromosome with bipolar illness have not been supported by others. More recently bipolar disorder has been reported to be linked with markers on chromosomes 18, 21, 16 and a region on the X chromosome different from those previously suggested. We have carried out a linkage study in twelve bipolar families. In a single family a genome search employing 193 markers indicated linkage on chromosome 4p where the marker D4S394 generated a two-point lod score of 4.1 under a dominant model of inheritance. Three point analyses with neighbouring markers gave a maximum lod score of 4.8. Eleven other bipolar families were typed using D4S394 and in all families combined there was evidence of linkage with heterogeneity with a maximum two-point lod score of 4.1 (theta = 0, alpha = 0.35).

Bipolar Disorder↗