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Biomedical subjects

A Hall

Publications and source records attributed to A Hall.

At least 37 records · Page 2Linked to original sources
PubMed2002

The imaging of paediatric thoracic trauma.

Trauma is a significant cause of morbidity and mortality in children and radiological investigations are almost always used in its management. This article reviews the radiological findings in thoracic trauma, in relation to their effects on lung parenchyma, the airways, the pleura, the great vessels, the diaphragms and the bony skeleton. Particular emphasis is given to plain radiographical and computed tomography findings, since these are the commonest imaging modalities used.

Bronchi↗
PubMed2002

Heavy schistosomiasis associated with poor short-term memory and slower reaction times in Tanzanian schoolchildren.

Cross-sectional studies of the relationship between helminth infection and cognitive function can be informative in ways that treatment studies cannot. However, interpretation of results of many previous studies has been complicated by the failure to control for many potentially confounding variables. We gave Tanzanian schoolchildren aged 9-14 a battery of 11 cognitive and three educational tests and assessed their level of helminth infection. We also took measurements of an extensive range of potentially confounding or mediating factors such as socioeconomic and educational factors, anthropometric and other biomedical measures. A total of 272 children were moderately or heavily infected with Schistosoma haematobium, hookworm or both helminth species and 117 were uninfected with either species. Multiple regression analyses, controlling for all confounding and mediating variables, revealed that children with a heavy S. haematobium infection had significantly lower scores than uninfected children on two tests of verbal short-term memory and two reaction time tasks. In one of these tests the effect was greatest for children with poor nutritional status. There was no association between infection and educational achievement, nor between moderate infection with either species of helminth and performance on the cognitive tests. We conclude that children with heavy worm burdens and poor nutritional status are most likely to suffer cognitive impairment, and the domains of verbal short-term memory and speed of information processing are those most likely to be affected.

Adolescent↗
PubMed2002

Pituitary autoantibodies in lymphocytic hypophysitis target both gamma- and alpha-Enolase - a link with pregnancy?

The first target autoantigen to have been identified in lymphocytic hypophysitis is a 49 kDa protein, identified as alpha-enolase. Pituitary autoimmunity is strongly associated with pregnancy and we have shown that pituitary autoantibodies from patients with peripartum lymphocytic hypophysitis also recognise enolase in the placenta. Enolase exists in different forms as a number of isoenzymes, which are homo- or heterodimers of three subunits, alpha, beta and gamma. alphaalpha-enolase is ubiquitous, betabeta-enolase is muscle-specific and gammagamma-enolase, which is restricted to neuronal tissue and neuroendocrine cells, is known as neuron-specific enolase (NSE). NSE is expressed in normal human pituitary and pituitary neoplasms. The current study investigated which isoforms of enolase in pituitary and placenta reacted with the sera of patients with lymphocytic hypophysitis. Immunoblotting of two-dimensional gels of human pituitary cytosolic proteins showed that autoantibodies in patient sera react with both an acidic form, and more neutral forms of enolase. Immunoblotting with a monoclonal antibody to NSE confirmed the identity of the acidic enolase isoform as the gammagamma-isoform in both pituitary and placental samples. Gamma-enolase, i.e. NSE, was detected by immunohistochemistry in term placenta in decidua, syncytiotrophoblasts, anchoring villi and terminal villi. Our study is the first to describe the cellular localisation of NSE in normal human placenta, thus establishing a direct link between pituitary and placental autoantigens. This link provides a theoretical basis for the strong prediliction of lymphocytic hypophysitis to occur during or after pregnancy.

Autoantibodies↗
PubMed2002

Schistosomiasis, helminth infection and health education in Tanzania: achieving behaviour change in primary schools.

Over a period of one school year a study was carried out into the feasibility and effectiveness of introducing active teaching methods into primary schools in Tanzania with a view to enhancing health education. The Lushoto Enhanced Health Education Project had as a focus personal hygiene with reference to the control of schistosomiasis and helminth infections. When a randomly selected group of children were compared with a comparison group there was evidence of changes in both knowledge and health-seeking behaviour. The passing of messages from children to the community met with mixed results. The observed changes were still evident over 1 year after the project had ended.

Child↗
PubMed2002

Do criminals go to the hospital when they are shot?

OBJECTIVES: To determine whether criminals go to the hospital when they are shot. Such information is needed to check on the accuracy of using hospital emergency room data to estimate non-fatal gunshot wounds. SETTING: Five jails across the US. METHODS: A survey of inmates being booked into jail, administered by in-house health care staff. RESULTS: Over 90% of over 300 criminals who had been wounded sometime before their incarceration reported going to a hospital for treatment after being shot. These results are consistent with previous findings from one jail. CONCLUSIONS: Jail inmates who had previously been shot were likely to have been treated in a hospital. This limited finding is consistent with the proposition that hospital/emergency department data may miss only a small percentage of gunshot wounds to criminals.

Adolescent↗
PubMed2001

Cdc42 induces filopodia by promoting the formation of an IRSp53:Mena complex.

BACKGROUND: The Rho GTPases Rho, Rac, and Cdc42 regulate the organization of the actin cytoskeleton by interacting with multiple, distinct downstream effector proteins. Cdc42 controls the formation of actin bundle-containing filopodia at the cellular periphery. The molecular mechanism for this remains as yet unclear. RESULTS: We report here that Cdc42 interacts with IRSp53/BAP2 alpha, an SH3 domain-containing scaffold protein, at a partial CRIB motif and that an N-terminal fragment of IRSp53 binds, via an intramolecular interaction, to the CRIB motif-containing central region. Overexpression of IRSp53 in fibroblasts leads to the formation of filopodia, and both this and Cdc42-induced filopodia are inhibited by expression of the N-terminal IRSp53 fragment. Using affinity chromatography, we have identified Mena, an Ena/VASP family member, as interacting with the SH3 domain of IRSp53. Mena and IRSp53 act synergistically to promote filopodia formation. CONCLUSION: We conclude that the interaction of Cdc42 with the partial CRIB motif of IRSp53 relieves an intramolecular, autoinhibitory interaction with the N terminus, allowing the recruitment of Mena to the IRSp53 SH3 domain. This IRSp53:Mena complex initiates actin filament assembly into filopodia.

3T3 Cells↗
PubMed2001

Evaluation of efficacy of school-based anthelmintic treatments against anaemia in children in the United Republic of Tanzania.

OBJECTIVE: To determine the impact of deworming on anaemia as part of a large-scale school-based anthelmintic treatment programme in the Tanga Region of the United Republic of Tanzania. METHODS: Both the reduction in the prevalence of anaemia and the cost per case prevented were taken into consideration. Cross-sectional studies involved parasitological examination and anaemia evaluation before and at 10 months and 15 months after schoolchildren were dewormed. FINDINGS: Baseline studies indicated that the prevalence of anaemia (haemoglobin < 110 g/l) was high (54%) among schoolchildren, particularly those with high intensities of hookworm and schistosomiasis. Attributable fraction analysis suggested that hookworm and schistosomiasis were responsible for 6% and 15% of anaemia cases, respectively. Fifteen months after deworming with albendazole and praziquantel the prevalence of anaemia was reduced by a quarter and that of moderate-to-severe anaemia (haemoglobin <90 g/l) was reduced by nearly a half. The delivery of these anthelmintics through the school system was achieved at the relatively low cost of US$ 1 per treated child. The cost per anaemia case prevented by deworming schoolchildren was in the range US$ 6-8, depending on the haemoglobin threshold used. CONCLUSIONS: The results suggested that deworming programmes should be included in public health strategies for the control of anaemia in schoolchildren where there are high prevalences of hookworm and schistosomiasis.

Albendazole↗
PubMed2001

Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta.

We describe here a signal transduction pathway controlling the establishment of mammalian cell polarity. Scratching a confluent monolayer of primary rat astrocytes leads to polarization of cells at the leading edge. The microtubule organizing center, the microtubule cytoskeleton, and the Golgi reorganize to face the new free space, and directed cell protrusion and migration specifically occur perpendicularly to the scratch. We show here that the interaction of integrins with extracellular matrix at the newly formed cell front leads to the activation and polarized recruitment of Cdc42, which in turn recruits and activates a cytoplasmic mPar6/PKCzeta complex. Localized PKCzeta activity, acting through the microtubule motor protein dynein, is required for all aspects of induced polarity in these cells.

Animals↗
PubMed2001

Rac mediates cytoskeletal rearrangements and increased cell motility induced by urokinase-type plasminogen activator receptor binding to vitronectin.

The urokinase-type plasminogen activator receptor (uPAR) is involved in the regulation of cell motility in a variety of cell types. We show here that expression of human uPAR in growing murine fibroblasts leads to a dramatic reorganization of the actin cytoskeleton. uPAR expression induces multiple rapidly advancing protrusions that resemble the leading edge of migrating cells. The cytoskeletal changes are independent of uPA and activation of the RGD-binding activity of integrins but require uPAR binding to vitronectin (VN). The actin reorganization is blocked by coexpression of dominant negative versions of either Rac (N17Rac) or p130Cas, but not by inhibitors of Cdc42 or Rho, and is accompanied by a Rac-dependent increase in cell motility. In addition, a fourfold increase in the level of activated Rac is induced by uPAR expression. We conclude that uPAR interacts with VN both to initiate a p130Cas/Rac-dependent signaling pathway leading to actin reorganization and increased cell motility and to act as an adhesion receptor required for these responses. This mechanism may play a role in uPAR-mediated regulation of cell motility at sites where VN and uPAR are co-expressed, such as malignant tumors.

3T3 Cells↗
PubMed2001

Plexin-B semaphorin receptors interact directly with active Rac and regulate the actin cytoskeleton by activating Rho.

Semaphorins and their receptors, plexins, are widely expressed in embryonic and adult tissues. In general, their functions are poorly characterized, but in neurons they provide essential attractive and repulsive cues that are necessary for axon guidance [1-3]. The Rho family GTPases Rho, Rac, and Cdc42 control signal transduction pathways that link plasma membrane receptors to the actin cytoskeleton and thus regulate many actin-driven processes, including cell migration and axon guidance [4-7]. Using yeast two-hybrid screening and in vitro interaction assays, we show that Rac in its active, GTP bound state interacts directly with the cytoplasmic domain of mammalian and Drosophila B plexins. Plexin-B1 clustering in fibroblasts does not cause the formation of lamellipodia, which suggests that Rac is not activated. Instead, it results in the assembly of actin:myosin filaments and cell contraction, which indicates Rho activation. Surprisingly, these cytoskeletal changes are both Rac and Rho dependent. Clustering of a mutant plexin, lacking the Rac binding region, induced similar cytoskeletal changes, and this finding indicates that the physical interaction of plexin-B1 with Rac is not required for Rho activation. Our findings that plexin-B signaling to the cytoskeleton is both Rac and Rho dependent form a starting point for unraveling the mechanism by which semaphorins and plexins control axon guidance and cell migration.

3T3 Cells↗
PubMed2001

An abrupt climate event in a coupled ocean-atmosphere simulation without external forcing.

Temperature reconstructions from the North Atlantic region indicate frequent abrupt and severe climate fluctuations during the last glacial and Holocene periods. The driving forces for these events are unclear and coupled atmosphere-ocean models of global circulation have only simulated such events by inserting large amounts of fresh water into the northern North Atlantic Ocean. Here we report a drastic cooling event in a 15,000-yr simulation of global circulation with present-day climate conditions without the use of such external forcing. In our simulation, the annual average surface temperature near southern Greenland spontaneously fell 6-10 standard deviations below its mean value for a period of 30-40 yr. The event was triggered by a persistent northwesterly wind that transported large amounts of buoyant cold and fresh water into the northern North Atlantic Ocean. Oceanic convection shut down in response to this flow, concentrating the entire cooling of the northern North Atlantic by the colder atmosphere in the uppermost ocean layer. Given the similarity between our simulation and observed records of rapid cooling events, our results indicate that internal atmospheric variability alone could have generated the extreme climate disruptions in this region.

Journal Article↗
PubMed2001

Prevalence of HBV core promoter/precore/core mutations in Gambian chronic carriers.

One hundred forty-two precore/core sequences were obtained from Gambian chronic hepatitis B virus (HBV) carriers and the predominant variants defined. The two point mutations, from A to T and G to A at nt positions 1762 and 1764 in the basic core promoter region, were found in only 7/99 (7%) of the samples where this region was sequenced. These mutations were found in both HBeAg-positive and -negative patients. The precore stop-codon mutation at nt position 1896 was found in 14/51 (27%) of HBeAg-negative samples, which is a lower prevalence rate in comparison with other parts of the world with high carrier rates. In HBeAg-positive patients the core amino acid sequences were conserved, but after seroconversion to anti-HBe significantly more changes were apparent. Several of the amino acid substitutions found have been described previously been in wild-type viruses of other genotypes.

Amino Acid Sequence↗
PubMed2001

Investigation of the permeability of humic molecules using zeta potential measurements.

Zeta potential measurements have been performed on colloidal humate in the presence of differing concentrations of sodium ions at pH = 6.0. A series of calculations has been performed in which the radius of the humic colloid was varied until the predicted surface potential was equal to the experimentally determined zeta potential. The results of the calculations showed that as the ionic strength increases, the apparent radius of the colloid decreases. Similar calculations in which a model colloid was treated as a rigid sphere, i.e., the radius of the colloid was kept constant, failed to simulate the observed zeta potential measurements.

Colloids↗
PubMed2001

Transmission of hepatitis B virus infection in Gambian families revealed by phylogenetic analysis.

BACKGROUND/AIMS: Transmission of hepatitis B virus (HBV) in Africa occurs horizontally, with most people becoming infected between the ages of 1 and 5 years. The index cases in such events have been assumed to come from within the family unit or from sources outside the immediate family, such as other families or inhabitants of the same compound or village. Here, we define these routes of transmission by phylogenetic tree analysis of sequences from the entire pre-core/core region of the virus, in Gambian chronic carriers. METHODS: Amplification by polymerase chain reaction of serum extracted HBV-DNA was followed by direct sequencing of the target region. Following editing and alignment of these sequences, phylogenetic tree analysis was performed using the neighbour-joining and maximum-likelihood methods. RESULTS: Despite the overall conserved nature of the sequences of the pre-core/core region from 142 chronic carriers, distinct clusters were easily defined at the family and village level, but not on a wider geographical separation. CONCLUSIONS: Phylogenetic tree analysis of sequences obtained from family members provided strong evidence of intrafamilial transmission of HBV in at least two-thirds of the families studied from Gambia.

Cluster Analysis↗
PubMed2001

Health and cultural factors associated with enrolment in basic education: a study in rural Ghana.

This inter-disciplinary study compares the health status of school-age children in Ghana, both enrolled and non-enrolled, and examines these results within a wider socio-economic and socio-cultural context including kinship and livelihood. Children matched for age and sex who were not enrolled in Primary School were significantly shorter and more stunted than enrolled children were, and 70% of all Primary school-age children were anaemic. Young children from farming communities were significantly more undernourished than children from fishing communities. Adolescent non-enrolled boys were more heavily infected with Schistosoma haematobium, and were more likely to be anaemic than enrolled adolescent boys. The data indicate how health and health related factors may influence and affect enrolment and how socio-economic indicators, livelihood, and kinship may also constrain enrolment and, in turn, affect child health. This study sheds light on the complex factors that may influence enrolment in education and provides novel data on the similarities and differences between the health of enrolled and non-enrolled children in rural Ghana.

Adolescent↗
PubMed2001

The effects of sex and age of responders on the reliability of self-diagnosed infection: a study of self-reported urinary schistosomiasis in Tanzanian school children.

Self-reported schistosomiasis has been proven to be a reliable estimation of the prevalence of infection in school children. For the first time, this paper presents an investigation into the use of self-reported schistosomiasis to estimate the prevalence of urinary schistosomiasis, due to Schistosoma haematobium, in school children with particular emphasis on whether the age and sex of respondents influences the reliability of diagnosis. It is shown first, that the prevalence and intensity of infection vary with sex; infection in boys is always more prevalent and more intense than in girls of the same age and second, that age and sex influence the reliability of self-reported schistosomiasis as a diagnostic method. Age and sex are factors that should be considered when implementing control measures in endemic areas.

Adolescent↗
PubMed2001

The C. elegans PH domain protein CED-12 regulates cytoskeletal reorganization via a Rho/Rac GTPase signaling pathway.

The C. elegans gene ced-12 functions in the engulfment of apoptotic cells and in cell migration, acting in a signaling pathway with ced-2 Crkll, ced-5 DOCK180, and ced-10 Rac GTPase and acting upstream of ced-10 Rac. ced-12 encodes a protein with a pleckstrin homology (PH) domain and an SH3 binding motif, both of which are important for ced-12 function. CED-12 acts in engulfing cells for cell corpse engulfment and interacts physically with CED-5, which contains an SH3 domain. CED-12 has Drosophila and human counterparts. Expression of CED-12 and its counterparts in murine Swiss 3T3 fibroblasts induced Rho GTPase-dependent formation of actin filament bundles. We propose that through interactions with membranes and with a CED-2/CED-5 protein complex, CED-12 regulates Rho/Rac GTPase signaling and leads to cytoskeletal reorganization by an evolutionarily conserved mechanism.

3T3 Cells↗