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Biomedical subjects

F Watson

Publications and source records attributed to F Watson.

At least 19 recordsLinked to original sources

Three centuries of stomach symptoms in Scotland.

BACKGROUND: Stomach pain and discomfort have been reported since antiquity. AIM: To follow the time trends since the 18th century of dyspepsia, gastric ulcer, duodenal ulcer, and benign oesophageal disease to test when dyspepsia started to become a major clinical problem. METHODS: The annual in- and out-patient records of the last three centuries from the Scottish Royal Infirmaries of Edinburgh, Aberdeen, Glasgow and Dundee were analysed. In addition, dispensary attendances, clinicians' casebooks, students' notebooks and medical texts have been scrutinized for historic statistics of upper gastrointestinal disease. RESULTS: Dyspepsia was first recorded in the 1750s and increased markedly subsequently. Such dyspepsia persisted after gastric and duodenal ulcers appeared in the late 19th century and then declined again in the late 20th century. Non-ulcer dyspepsia has remained the commonest diagnosis made after endoscopy for stomach pain in the beginning of the 21st century. CONCLUSION: The current commonest diagnosis of stomach pain, dyspepsia dates from the mid-18th century. Any explanations of its causation need to consider this timing.

Ambulatory Care↗

Why do women decline prenatal screening and diagnosis? Australian women's perspective.

In this paper, we examine reasons for declining both prenatal screening, and diagnosis among a small group of pregnant women in Victoria, Australia. Semi-structured questionnaires were used to elicit women's account of their refusals of offers during pregnancy. Previous literature suggests that women decline prenatal screening and diagnosis because they are against abortion and the medicalisation of pregnancy, and have conoerns about the health and well-being of their fetuses. Women in this study had similar reasons but they also had other reasons for declining. Most clearly was that related to 'risk' brought about by the prospect of knowledge gained from undertaking prenatal screening and diagnostic tests, which would cause emotional distress and lead to further difficult decisions. The results have implications for the development and expansion of prenatal screening and diagnosis for pregnant women in Australia and elsewhere. We are not suggesting that prenatal screening and diagnosis is a problem for all women or even most women. However, health service providers must provide information about prenatal screening and diagnosis that is appropriate for all pregnant women, presenting all options, including that of not having any screening or diagnostic test. In doing so we will be facilitating the opportunity for women to make an informed choice and acknowledging the existence and importance of this small, but concerned group of women.

Adult↗

Transcriptional activation of the rat vesicular monoamine transporter 2 promoter in gastric epithelial cells: regulation by gastrin.

Vesicular monoamine transporter 2 is important for the accumulation of monoamine neurotransmitters into synaptic vesicles and histamine transport into secretory vesicles of the enterochromaffin-like cell of the gastric corpus. In this study we have investigated the mechanisms regulating the transcriptional activation of the rat vesicular monoamine transporter 2 (VMAT2) promoter in gastric epithelial cells. Maintenance of basal levels of transcription was dependent on the presence of SP1, cAMP-response element (CRE), and overlapping AP2/SP1 consensus sequences within the region of promoter from -86 to +1 base pairs (bp). Gastrin stimulation increased transcriptional activity, and responsiveness was shown to be dependent on the CRE (-33 to -26 bp) and AP2/SP1 (-61 to -48 bp) consensus sites but independent of the SP1 site at -86 to -81 bp. Gastrin-induced transcription was dependent on the cooperative interaction of an uncharacterized nuclear factor of approximately 23.3 kDa that bound to the putative AP2/SP1 site, CRE-binding protein (CREB), and CREB-binding protein/p300. Gastrin stimulation resulted in the increased binding of phosphorylated CREB to the promoter, but it did not result in the increased binding of the AP2/SP1-binding protein. The gastrin responsiveness of the promoter was shown to be dependent on both the protein kinase C and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-signaling pathways, which may converge on the AP2/SP1-binding protein.

Adenovirus E1A Proteins↗

Seasonality of eating pathology on the eating attitudes test in a nonclinical population.

OBJECTIVE: To determine whether there are seasonal fluctuations in eating pathology in a nonclinical population. METHOD: The Eating Attitudes Test (EAT) was completed by 322 subjects during winter and again during summer. Summer and winter responses were compared to investigate differences in EAT total and subscale scores and for individual EAT items. Numbers of subjects fluctuating across the seasons by more than 2 SDs of the cohort's scores were identified. RESULTS: The cohort showed no significant seasonal change on EAT-40 totals, EAT-26 totals, or within the EAT subscales. There were significant (p <.025) seasonal fluctuations on four of the EAT-40 questions. For individual respondents, there was no greater likelihood of scoring significantly higher in the winter than in the summer. DISCUSSION: Clinically significant seasonal fluctuations in eating pathology on the EAT did not occur in this nonclinical population. It is debatable whether items within the EAT which show significant seasonal fluctuations should be retained or discarded.

Adult↗

Transcriptional activation of vesicular monoamine transporter 2 in the pre-B cell line Ea3.123.

Uptake and storage of monoamines in secretory granules is accomplished by vesicular monoamine transporters, and it is likely that vesicular monoamine transporter 2 (VMAT2) is important for histamine transport in vivo. In the present study we have used the pre-B-cell line Ea3.123 to investigate the mechanisms involved in the transcriptional activation of the VMAT2 gene. In Ea3.123 cells, VMAT2 mRNA abundance was increased following mobilization of intracellular calcium, and this increased mRNA expression was paralleled by changes in l-histidine decarboxylase mRNA, suggesting that VMAT2 may be responsible for sequestration of histamine into secretory vesicles in this cell line. We cloned the 5'-flanking region of the VMAT2 gene and determined its transcriptional start site by primer extension of rat VMAT2 mRNA. There was no TATA or TATA-like sequence upstream of this region; instead there were GC-rich elements, Ca2+/cAMP-response-element- and SP1-binding motifs. Approx. 900 bp upstream of the transcriptional start site was a purine-pyrimidine repeat sequence that may form a Z-DNA structure. A series of 5'-deletional VMAT2-promoter segments cloned upstream of a luciferase reporter were capable of driving transcription and indicated the presence of multiple regulatory elements, while stimulation with ionomycin or PMA resulted in an increased level of the transcriptional activity of the 5'-promoter segments studied.

Animals↗

Stimulation of primed neutrophils by soluble immune complexes: priming leads to enhanced intracellular Ca2+ elevations, activation of phospholipase D, and activation of the NADPH oxidase.

Soluble immune complexes activate a rapid burst of reactive oxidant secretion from neutrophils that have previously been primed with GM-CSF. Binding of these complexes to the cell surface of unprimed neutrophils results in the generation of intracellular Ca2+ transients, but the NADPH oxidase fails to become activated. No phospholipase D activity was observed following the addition of soluble immune complexes to unprimed cells. Upon priming with GM-CSF, the intracellular Ca2+ signal generated following soluble complex binding was greatly extended and phospholipase D was activated: there was also increased phosphorylation of proteins on tyrosine residues and the NADPH oxidase was activated. When Ca2+ influx was prevented, this phospholipase D activity was not observed. This primed oxidase activity was completely inhibited by erbstatin. Treatment of unprimed neutrophils with pervanadate (to inhibit protein tyrosine phosphatases) mimicked the effects of priming in that pervanadate-treated neutrophils secreted reactive oxidants in response to soluble immune complexes. The data indicate that during priming a new signaling pathway is activated that involves Ca2+ influx, phosphorylation on tyrosine residues, phospholipase D activity, and NADPH oxidase activation.

Aniline Compounds↗

Activation of human neutrophils by soluble immune complexes: role of Fc gamma RII and Fc gamma RIIIb in stimulation of the respiratory burst and elevation of intracellular Ca2+.

Activation of control, unprimed neutrophils with soluble immune complexes fails to generate a respiratory burst. However, if the cells are primed with either tumor necrosis factor-alpha or granulocyte-macrophage colony-stimulating factor prior to addition of soluble immune complexes, then a rapid and transient burst of reactive oxidant secretion is observed. In unprimed neutrophils the soluble immune complexes stimulate an intracellular Ca2+ transient that arises from the mobilization of intracellular Ca2+. However, in primed cells, an "extra" intracellular Ca2+ signal is observed that arises from Ca2+ influx. After removal of Fc gamma RIIIb by treatment with pronase or PI-PLC, the soluble immune complexes fail to activate a respiratory burst in unprimed neutrophils and the "extra" Ca2+ signal is not observed. These results indicate that during priming Fc gamma RIIIb becomes functionally activated and thence its ligation leads to stimulated Ca2+ influx and the generation of intracellular signals that lead to NADPH oxidase activation. Experiments using Fab/F(ab')2 fragments to specifically crosslink either Fc gamma RII or Fc gamma RIIIb and experiments with neutrophils from an individual with Fc gamma RIIIb gene deficiency confirm this important function for Fc gamma RIIIb in neutrophil activation.

Antibodies, Monoclonal↗

Stimulation of intracellular Ca2+ levels in human neutrophils by soluble immune complexes. Functional activation of FcgammaRIIIb during priming.

Soluble immune complexes bind to unprimed neutrophils and generate intracellular Ca2+ transients but fail to activate the NADPH oxidase. Following priming of the neutrophils with either tumor necrosis factor alpha or granulocyte-macrophage colony-stimulating factor, stimulation of the cells with the soluble immune complexes leads to an enhanced Ca2+ signal and significant secretion of reactive oxidants. The enhanced Ca2+ signal observed in primed neutrophils results from the influx of Ca2+ from the external environment and is partly sensitive to tyrosine kinase inhibitors. This is in contrast to the Ca2+ signal observed in unprimed neutrophils, which arises from the mobilization of intracellular stores. When the surface expression of FcgammaRIIIb on primed neutrophils was decreased either through incubation with Pronase or phosphoinositide-specific phospholipase C, the extra enhanced Ca2+ mobilization seen in primed cells was significantly lowered, while the initial rise in intracellular Ca2+ was unaffected. Depletion of FcgammaRIIIb had no significant effect on the Ca2+ transients in unprimed neutrophils. Cross-linking FcgammaRII, but not FcgammaRIIIb, induced increases in intracellular Ca2+ in unprimed neutrophils, while cross-linking either of these receptors increased Ca2+ levels in primed neutrophils. The FcgammaRII-dependent intracellular Ca2+ rise in primed cells was unaffected by incubation in Ca2+-free medium, whereas the FcgammaRIIIb-dependent transient was significantly decreased when Ca2+ influx was prevented in Ca2+-free medium supplemented with EGTA. Cross-linking either FcgammaRII or FcgammaRIIIb in primed or unprimed cells failed to stimulate substantial levels of inositol 1,4,5-trisphosphate production. These results indicate that following stimulation of primed neutrophils with soluble immune complexes the enhanced Ca2+ mobilization observed is the result of a functional activation of the glycosylphosphatidylinositol-linked FcgammaRIIIb.

Animals↗

Regulated expression of GATA-6 transcription factor in gastric endocrine cells.

BACKGROUND & AIMS: GATA transcription factors may regulate gene expression in developing tissues, including gut epithelium. In the stomach, their expression has been linked to regulation of proton pump genes. However, GATA consensus sequences also occur in the promoter of the histidine decarboxylase gene, located in enterochrommafin-like cells. The aim of this study was to determine if GATA factors are located in gastric endocrine cells and to examine their expression during development and in response to changes in the gastric luminal environment. METHODS: Polymerase chain reaction cloning, Northern blot, and gel shift assays were used to examine GATA expression in gastric endocrine cells; changes in GATA messenger RNA during development and in response to fasting, feeding, and gastric achlorhydria were determined by Northern blot. RESULTS: GATA-6 was expressed strongly in rodent gastric endocrine cell fractions, in a human ECL cell tumor, and in an endocrine cell line (STC-1) derived from gut epithelium; proteins from STC-1 cells bound specifically to GATA consensus sequences in the human histidine decarboxylase promoter. GATA messenger RNA abundance was up-regulated during terminal differentiation of the rat stomach and on feeding after a fast. CONCLUSIONS: The GATA-6 transcription factor is expressed in gastric endocrine cells and is a potential regulator of gastric differentiation and of genes involved in the response to feeding.

Achlorhydria↗

Neutrophils from the synovial fluid of patients with rheumatoid arthritis express the high affinity immunoglobulin G receptor, Fc gamma RI (CD64): role of immune complexes and cytokines in induction of receptor expression.

Neutrophils isolated from the synovial fluid of 16/24 patients with rheumatoid arthritis expressed Fc gamma RI (CD64), the high-affinity receptor for monomeric immunoglobulin G (IgG), on their cell surface. Receptor expression ranged from 17% to 168% of the level of expression obtained after incubation of control blood neutrophils with 100 U/ml interferon-gamma (IFN-gamma) for 24 hr in vitro. Similarly, mRNA for Fc gamma RI was detected in synovial fluid neutrophils from 12/15 patients and transcript levels ranged from 5% to 200% of the values obtained after treatment of blood neutrophils with IFN-gamma for 4 hr in vitro. No surface expression nor mRNA were detected in freshly isolated blood neutrophils from either patients or from healthy controls. Addition of cell-free synovial fluid to control blood neutrophils induced both mRNA and surface expression of Fc gamma RI to levels that were comparable to those achieved after addition of IFN-gamma. Neither soluble nor insoluble immune complexes appeared to be involved in induction of Fc gamma RI expression in spite of the ability of these complexes to induce protein biosynthesis. Synovial fluid-induced expression of Fc gamma RI was partially blocked by incubation with neutralizing IFN-gamma antibodies, whilst neutralizing interleukin (IL)-6 antibodies had little effect. Levels of IFN-gamma measured within these synovial fluids ranged from 0 to 2.7 U/ml, well within the range known to induce neutrophil Fc gamma RI expression. These data thus indicate that gene expression in synovial fluid neutrophils is selectively activated as the cells enter the diseased joint. Furthermore, these data indicate that induced expression of Fc gamma RI may alter the ability of infiltrating neutrophils to respond to IgG-containing immune complexes present in these joints.

Antigen-Antibody Complex↗

Stimulation of primed neutrophils by soluble immune complexes.

Soluble IgG-containing immune complexes are unable to initiate oxidant production in unprimed neutrophils. However, priming of the neutrophils with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or cytochalasin B prior to exposure to these complexes results in activation of a rapid and extensive secretion of reactive oxidants. In this study, we have investigated the ability of soluble immune complexes to: (1) induce oxidant generation; (2) bind to the cell surface; and (3) induce Ca2+ transients in neutrophils primed by incubation with GM-CSF or cytochalasin B. Our findings give new insight into the molecular processes involved in the "priming" phenomenon.

Antigen-Antibody Complex↗

Phospholipases Involved in Activation of the Neutrophil NADPH Oxidase

Stimulation of neutrophils with a variety of stimuli can result in the activation of phospholipases A2, C, or D with the resultant hydrolysis of plasma membrane phospholipids and the formation of important second messenger molecules. In the neutrophil, the activities of these phospholipases have been implicated in the processes of both stimulating and maintaining oxidase activation. In this review, some of the methods currently used to measure the products of phospholipase activation in the neutrophil are described, along with the possible role of their products in reactive oxidant production by the neutrophil NADPH oxidase.

Journal Article↗

Who is nutritionally vulnerable in Bosnia-Hercegovina?

OBJECTIVE: To monitor nutritional status and food security in order to identify nutritionally vulnerable groups. DESIGN: Members of five different household groups (urban and rural residents, displaced people in collective centres and private accommodation, elderly people living without younger family) and all residents of two old people's homes were prospectively followed. Households were selected from 20 local communities and nine collective centres. SETTING: Monitoring carried out in three besieged areas of Bosnia-Hercegovina (Sarajevo, Tuzla, and Zenica). SUBJECTS: 1739 individuals sampled. INTERVENTIONS: Data collected every month from December 1993 to May 1994. Information on household food security was collected through structured questionnaires. All subjects were weighed and their heights measured. Weight for age Z scores were calculated for children; body mass index was calculated for adults and elderly people. RESULTS: From December 1993 to February 1994, before a temporary cease fire, access to food was reduced. In February 1994 no significant signs of undernutrition were detected among children or adults, but elderly people had higher than expected levels of undernutrition (15.5% with body mass index < 18.5), a higher rate of weight loss than adults (1.2 kg over two months), and a higher prevalence of self reported illness. CONCLUSIONS: Elderly people in Bosnia-Hercegovina are at greater risk of undernutrition than other age groups. Undernutrition may be precipitated in elderly people by sickness, cold, stress, and problems related to food preparation. The health and welfare of elderly people during the emergency in Bosnia-Hercegovina require special attention, and integrated age care programmes are needed.

Adolescent↗

The impact of a reduced and uncertain food supply in three besieged cities of Bosnia-Hercegovina.

Nutritional status and household food security were longitudinally monitored in three besieged cities of Bosnia-Hercegovina (Sarajevo, Zenica and Tuzla) during the winter and spring of 1993 to 1994. The objectives were to provide early warning of a deterioration in the food and nutrition situation and identify particularly vulnerable groups so that action could be taken to prevent potential undernutrition and target resources to the most needy. Before the cease-fire, which came into effect at the end of February 1994, trends in various indicators (weight loss, decline of household food stocks, rising food prices, reduction in food aid distribution, sale of possessions) suggested that the situation was deteriorating. Access to food improved as a result of the cease-fire, however, which was reflected in improvements in indicators of food security and weight gain. The impact of, and response to, the food emergency differed between individuals, households and locations; the elderly were found to be more nutritionally vulnerable than children or adults, households with the least access to resources were the most food insecure, while the city of Zenica appeared to be particularly hard hit. The findings show the effects of an uncertain and reduced food supply on a previously well-fed healthy population in an industrialised country. The value and constraints of an Early Warning System set up to monitor trends in an emergency in a European context are discussed.

Adult↗

Nutritional status and food security: winter nutrition monitoring in Sarajevo 1993-1994.

OBJECTIVE: To monitor nutritional status and food security throughout the winter of 1993-1994 in order to provide early warning of any deterioration, identify the nutritionally vulnerable and so enable humanitarian agencies to respond appropriately. DESIGN: Four different household groups were prospectively followed: residents, refugees in collective centres, refugees in private accommodation and elderly living alone (either residents or refugees). Four local communities were purposively selected and two collective centres were randomly selected. Households were randomly selected within each community and collective centre. An additional sample of all elderly inhabitants of the old people's home were nutritionally assessed only. SETTING: Monitoring was implemented in the besieged city of Sarajevo. SUBJECTS: 143 households with 90 children (< 18 years), 230 adults (18-59 years), and 94 elderly (60 + years) members, and 40 elderly inhabitants of the old people's home were monitored. INTERVENTIONS: Every month from December 1993 to March 1994, information on household food security was collected through structured questionnaires. All subjects were weighed and their heights measured. Weight for age Z scores in children (six months to 12 years) and body mass index (BMI) in adults and the elderly were calculated. RESULTS: While the nutritional status of adults and children consistently remained normal, high levels of undernutrition were detected among the elderly ranging from 16% to 21% (BMI < 18.5). Between December 1993 and February 1994, adults lost an average of 260 grams in weight (paired t test p = 0.005). Indicators of household food security (food stocks per person, market food prices and access to food aid) showed negative trends during the same time period. CONCLUSIONS: Whilst there was no nutritional disaster in Sarajevo over the winter 1993-1994, there were signs that capacity to cope was weakening in some groups. The elderly were identified as the most nutritionally vulnerable due to sickness, cold, stress and problems related to food preparation. The most food insecure group were refugees in collective centres who were highly dependent on food aid, were less likely to have relatives outside Sarajevo to support them, had fewer possessions to sell and were least likely to have gardens.

Adolescent↗