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Biomedical subjects

S Thompson

Publications and source records attributed to S Thompson.

At least 127 records · Page 7Linked to original sources

Anterograde but not retrograde memory loss following combined mammillary body and medial thalamic lesions.

We report the first human case of combined mammillary body and medial thalamic lesions due to focal pathology. A patient presented with a multi-lobular lesion that affected the mammillary bodies, the medial thalamus and the brain stem. On neuropsychological testing, he showed significant anterograde memory impairment, with marked impairment on delayed story recall, but normal or only mildly impaired performance on retrograde memory tasks. Our findings corroborate the results of recent non-human lesion studies and indicate that some of the well-established features of the amnesic syndrome, such as severe retrograde amnesia, may not be due to primary diencephalic pathology. Significant retrograde amnesia may result from cortical pathology or from an interaction between cortical and subcortical pathology.

Adult↗

Light activatable antibodies: models for remotely activatable proteins.

The ability to activate biological macromolecules remotely, at specific locations and times, will allow the manipulation of a wide range of cellular activities and give rise to many practical applications. Interest has been shown in the theoretical possibility of accomplishing this by means of photochemical approaches. Photochemical changes of the guest-binding cavity of cyclodextrins has been suggested; however, these changes require organic solvent. What is needed is a widely and readily applicable method allowing activation under physiological conditions. We have developed such a method. This is based on our demonstration that relatively large amounts of the a-methyl substituted 2-nitrobenzyl alcohol, namely, 1-(2-nitrophenyl)ethanol (NPE) can be coupled to proteins using diphosgene. Previous work involved "caging" of small molecules such as ATP (ref. 5-9) and blocking amino acids in peptide synthesis with 2-nitrobenzyl compounds. For large molecules, site-specific reversible inactivation of T4-lysozyme has been reported following introduction of an aspartyl beta-nibenzyl ester into its active site by mutagenesis. In contrast, the present simple procedure allows an existing protein to be deactivated and then, when and where required, reactivated by exposure to ultraviolet-A (UV-A) light. We have employed antibodies as models for both receptors and ligands and have successfully modulated: antibody binding sites for antigen; antigen binding sites for antibody, and antibody Fc binding sites for Protein A.

Antibodies↗

Time-based lag sequential analysis and the functional assessment of challenging behaviour.

This paper describes the application of time-based lag sequential analysis to the functional assessment of challenging behaviours shown by people with severe learning disabilities. The potential uses of the approach are illustrated with regards to identifying: (1) aspects of the stimulus control of challenging behaviour; (2) antecedents to the occurrence of challenging behaviour; and (3) the environmental consequences of challenging behaviour. The uses and limitations of the approach are discussed.

Adolescent↗

A comparison of transplant patient and social worker attitudes in regard to transplant patient psychosocial selection criteria, role expectations and communication style.

Though much is known about organ transplant (TX) patient and family psychosocial needs, there is virtually no information about the nature of the interaction that exists between TX social workers and patients. A comparison of TX patient-social worker attitudes and beliefs found (i) patients supported a more egalitarian "consumer-centered" approach to health care, but were reluctant to assume the accompanying responsibility, and (ii) social workers were more "traditional" in their approach, which focused primarily on assessment and social support. Results argue for a more comprehensive clinical approach by social workers to deal with problems of patient compliance, substance abuse, and psychological needs in a TX service where emphasis is placed on results rather than subjective process measures.

Adult↗

Retrospective Comparison of a Strategy of Primary Coronary Angioplasty versus Intravenous Thrombolytic Therapy for Acute Myocardial Infarction in a Community Hospital without Cardiac Surgical Backup.

Recent studies have demonstrated the benefit of primary percutaneous coronary angioplasty (PTCA) for the emergency treatment of acute myocardial infarction. We retrospectively examined our experience in performing primary PTCA in a community hospital without in-hospital surgical backup. Only highly experienced angioplasty operators participated, and patients were immediately transferred to a tertiary care referral hospital following primary angioplasty and stabilization. A total of 102 patients received PTCA at the community hospital during the study period. Forty received PTCA for cardiogenic shock or for rescue angioplasty. The remaining 62 patients (the Primary Angioplasty Group) were compared with a matched group of patients who received thrombolytic therapy during the same time period (the Thrombolytic Therapy Group). Angioplasty was angiographically successful in 96% and TIMI-3 grade blood flow was achieved in 85% of patients who received PTCA. There were no significant differences between the two groups in terms of in-hospital complications. The duration of hospital stay was significantly less in the Primary Angioplasty Group as compared with the Thrombolytic Therapy Group (median = 4 vs. 6 days, p = 0.005), as was the duration of intensive care unit stay (median 1 vs. 2.5 days, p = 0.001). Thus, under carefully controlled conditions, primary angioplasty for acute myocardial infarction in a community hospital without in-hospital cardiac surgery is an effective and more efficient alternative to thrombolytic therapy.

Journal Article↗

The psychological impact of cardiovascular screening and intervention in primary care: a problem of false reassurance? British Family Heart Study Group.

BACKGROUND: There have been many reports of the adverse psychological effects of screening. Here we discuss the results of a randomized controlled study--one of the first to address this issue. AIM: To determine the extent to which participation in a population-based intervention programme that aims to reduce the risk of cardiovascular diseases raises concerns about health, or undermines a belief in the ability to reduce that risk. METHOD: A randomized controlled trial involving 13 general practices in England, Wales and Scotland was conducted. Two thousand, nine hundred and eighty-four middle-aged men and women undergoing cardiovascular risk-screening and intervention, and a randomized comparison group of 3,576 men and women from the same practices, who were not offered the intervention, were compared on three outcomes: perception of current health, perceived risk of suffering a heart attack, and perceived ability to reduce the risk of suffering a heart attack. RESULTS: We found no evidence to suggest that participation in this one-year, population-based intervention programme, to reduce the risk of cardiovascular disease raised concerns about health or risk of a heart attack; indeed, those in the intervention group were slightly more optimistic about their health. Alterations in perceptions of current health and the risk of suffering a heart attack were associated directly with true alterations in risk factors. A more noticeable effect on participants in this intervention programme was a reduction in their perceived ability to further reduce their risks of a heart attack. This was associated with a decrease in weight and with quitting smoking. CONCLUSION: Contemporary screening and intervention programmes in primary care, aimed at reducing risk of cardiovascular disease, do not necessarily lead to raised anxiety or concern about health. A more subtle effect of screening would appear to be one of reassurance in the face of continuing, albeit reduced, risk.

Adaptation, Psychological↗

pop-1 encodes an HMG box protein required for the specification of a mesoderm precursor in early C. elegans embryos.

In C. elegans embryogenesis, the MS blastomere produces predominantly mesodermal cell types, while its sister E generates only endodermal tissue. We show that a maternal gene, pop-1, is essential for the specification of MS fate and that a mutation in pop-1 results in MS adopting an E fate. Previous studies have shown that the maternal gene skn-1 is required for both MS and E development and that skn-1 encodes a transcription factor. We show here that the pop-1 gene encodes a protein with an HMG box similar to the HMG boxes in the vertebrate lymphoid-specific transcriptional regulators TCF-1 and LEF-1. We propose that POP-1 and SKN-1 function together in the early embryo to allow MS-specific differentiation.

Amino Acid Sequence↗

Mutation of a highly conserved base in the yeast mitochondrial 21S rRNA restricts ribosomal frameshifting.

A mutation shown to cause resistance to chloramphenicol in Saccharomyces cerevisiae was mapped to the central loop in domain V of the yeast mitochondrial 21S rRNA. The mutant 21S rRNA has a base pair exchange from U2677 (corresponding to U2504 in Escherichia coli) to C2677, which significantly reduces rightward frameshifting at a UU UUU UCC A site in a +1 U mutant. There is evidence to suggest that this reduction also applies to leftward frameshifting at the same site in a -1 U mutant. The mutation did not increase the rate of misreading of a number of mitochondrial missense, nonsense or frameshift (of both signs) mutations, and did not adversely affect the synthesis of wild-type mitochondrial gene products. It is suggested here that ribosomes bearing either the C2677 mutation or its wild-type allele may behave identically during normal decoding and only differ at sites where a ribosomal stall, by permitting non-standard decoding, differentially affects the normal interaction of tRNAs with the chloramphenicol resistant domain V. Chloramphenicol-resistant mutations mapping at two other sites in domain V are described. These mutations had no effect on frameshifting.

Amino Acid Sequence↗

Comparison of echocardiographic variables between type I diabetics and normal controls.

This report compares echocardiographic estimates of systolic and diastolic function and ventricular dimensions in type I diabetics and normal controls. A random sample of 60 diabetics selected from a central hospital diabetic clinic was compared with a sample of 40 nondiabetic controls, and matched to the diabetics by age, gender, and blood pressure. Simple comparisons showed that diabetics had a higher mean resting heart rate (HR) (p < 0.001) and a slower diastolic early filling phase (maximal rate of increase in left ventricular dimension in early diastole [v/dtmax], p = 0.08; time from end-systole until dv/dtmax [ES-dv/dtmax], p = 0.03), which were explained by differences in HR and other factors. Resting HR was significantly associated with several echocardiographic variables, but the slope relating resting HR to ventricular dimension was more negative in diabetics than in controls (end-diastolic diameter, p < 0.008; end-systolic diameter, p < 0.005), and the ratio of systolic to diastolic duration was significantly (p < 0.01) less positive in diabetics. The association of resting HR to duration of isovolumic diastole was positive in diabetics and negative in controls (p < 0.02). Among diabetics, those with higher resting HR had more retinopathy (p < 0.05), microalbuminuria (p < 0.05), smaller ventricles (p < 0.01), and longer isovolumic diastole (p < 0.05). Poorer diabetic control was associated with poorer systolic (fractional shortening, p < 0.05) and diastolic (dv/dtmax, p < 0.05; ES-dv/dtmax, p < 0.05) function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Glycosylation of alpha-1-proteinase inhibitor and haptoglobin in ovarian cancer: evidence for two different mechanisms.

The change in glycosylation of the two acute-phase proteins, alpha-1-proteinase inhibitor (API) and haptoglobin (Hp), in progressive ovarian cancer is different. This has been shown by monosaccharide analysis and lectin-binding studies of proteins purified from serum. In the glycan chains of API, there is decreased branching (more biantennary chains), less branches ending in alpha 2-3 sialic acid, more branches ending in alpha 2-6 sialic acid and more fucose, probably linked alpha 1-6 to the core region. On the other hand, Hp shows increased branching (more triantennary chains), more branches ending in alpha 2-3 sialic acid, less branches ending in alpha 2-6 sialic acid, and more fucose, probably in the alpha 1-3 linkage at the end of the chains. This is surprising because API and Hp are thought to be glycosylated by a common pathway in the liver. We have also shown that the fucose-specific lectin, lotus tetragonolobus, extracts abnormal forms of both Hp and API in ovarian cancer, but the expression of this Hp is related to tumour burden and the expression of this API is related to lack of response to therapy. It is suggested that this difference in the behaviour of API and Hp in ovarian cancer may be associated with the different changes in their glycosylation. Of the many mechanisms that could explain these findings, a likely one is that a pathological process is removing API with triantennary chains from the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbohydrate Conformation↗

A prevalence study of ear problems in school children in Kiambu district, Kenya, May 1992.

Information on the prevalence of hearing impairment and related ear pathologies in children in sub-Saharan Africa is scarce. A pilot study for a clinical trial of simple treatments for chronic suppurative otitis media (CSOM) in school children in Kiambu district, Kenya, provided information on the prevalence of hearing impairment and ear pathologies. Five-thousand-three-hundred-sixty-eight children from 57 randomly chosen primary schools in Kiambu district were examined. Simple otoscopy was performed by clinical officers with specialty training in ENT, and hering testing was performed by trained nurses, using a hand held field audiometer. Microbiological specimens were obtained from those children with CSOM. Five-point-six percent of the children had a hearing impairment of > 30 dB HL in one or both ears, with 2.2% having bilateral hearing impairment. Two-point-four percent had at least one perforated tympanic membrane, and 1.1% had CSOM. Eight-point-six percent of the children had wax obstructing the tympanic membrane. There is evidence of a relationship between hearing impairment and both CSOM and wax obstructing the tympanic membrane. The most common organisms found were Pseudomonas spp. (34%), Proteus spp. (34%) and Eschericia coli (19%). These results are comparable with other studies in Africa and indicate a considerable burden of ear disease in Kiambu district, Kenya.

Adolescent↗

Functional enuresis: is desmopressin the answer?

OBJECTIVE: The efficacy of desmopressin in the treatment of functional enuresis, known for 15 years, has received very little attention in the psychiatric literature. This review seeks to remedy this and to asses critically its effectiveness, risks and side effects, as well as the implications for the understanding and management of enuresis. METHOD: Treatment trials, reports of unwanted effects, and literature on mechanisms of action were reviewed. RESULTS: Desmopressin is more effective than placebo in controlled trials, but only one quarter of patients become "dry." Individuals who wet the bed 4 nights per week or more can expect a one-third reduction in their wet nights with a single intranasal dose of desmopressin before bedtime. Relapse rates upon cessation of treatment are very high, while side effects appear to be few. However, there are increasing reports of hyponatremic seizures. There is a group of patients in which bed-wetting appears to be the result of insufficient nocturnal secretion of vasopressin. CONCLUSIONS: Desmopressin is a simple-to-use and effective drug for the treatment of nocturnal enuresis; it has opened important new avenues of inquiry, but more information is required about its long-term effectiveness and unwanted side effects.

Child↗

An N-Terminal Dimerization Domain Permits Homeodomain Proteins To Choose Compatible Partners and Initiate Sexual Development in the Mushroom Coprinus cinereus.

The A mating-type locus of the mushroom Coprinus cinereus contains three or more paralogous pairs of genes encoding two families of homeodomain proteins (HD1 and HD2). A successful mating brings together different allelic forms of at least one gene, and this is sufficient to trigger initial steps in sexual development. Previous studies have suggested that development is regulated by heterodimerization between HD1 and HD2 proteins. In this report, we describe 5[prime] gene deletions and 5[prime] end exchanges showing that the N-terminal regions of the proteins are essential for choosing a compatible partner but not for regulating gene transcription. Using an in vitro glutathione S-transferase association assay, we demonstrated heterodimerization between HD1 and HD2 proteins and found that heterodimerization only occurs between compatible protein combinations. The N-terminal regions of the proteins were sufficient to mediate dimerization, and N-terminal swaps resulted in a predicted change in dimerization specificity. By analyzing the N-terminal amino acid sequences of HD1 proteins, we identified two potential coiled-coil motifs whose relative positions vary in paralogous proteins but are both required for in vivo function.

Journal Article↗

Comparison of growth rates of bovine retinal and brain microvascular pericytes in different oxygen concentrations in vitro.

BACKGROUND: The hyperoxic injury of the microcirculation in the central nervous system appears to be specific to the retina in premature mammals. Oxygen tensions in normal adult mammalian retina and brain vary between nearly 0 and 90 mmHg. This study sought to compare the in vitro replication of retinal and brain microvascular pericytes in normal glucose medium and in 1%, 5% and 20% oxygen (equivalent to 15 mmHg, 35 mmHg and 150 mmHg, respectively). METHODS: A preliminary study, using oxygen microelectrodes, confirmed that the pericellular oxygen tension of pericytes, cultured in medium under air, was within 13 mmHg of the tension of the gas phase above the media. Pericytes were highly enriched by magnetic antibody cell sorting with the anti-pericyte monoclonal antibody (3G5) to 95% to 99% purity, to remove cell contaminants which may have invalidated the mitogenic assay. RESULTS: Mitogenic assays showed that brain pericytes replicated faster than their counterparts from retina (P < 0.0001, averaged for data from all culture conditions using three-way ANOVA). Reduction of oxygen tension from 150 to 15 mmHg led to significantly increased replication of retinal pericytes (P = 0.01), but an insignificant increase for brain pericytes. CONCLUSIONS: We have found that pericytes from the brain and retina cultured conventionally in fetal calf serum consume a relatively low amount of oxygen. Decreasing the oxygen tension to 1% (15 to 20 mmHg) increased the replication of retinal pericytes but not brain pericytes in normal glucose concentrations and in fetal calf serum. That retinal pericyte replication is sensitive to variation in oxygen tensions, indicates that the retinal microvascular cells have a unique biological response. This growth sensitivity to oxygen may be important in the pathogenesis of retinopathy of prematurity.

Animals↗